Thursday, October 18, 2012

SOLAR ENERGY

SOLAR ENERGY -- THE ENERGY OF THE FUTURE? About 47 per cent of the energy that the sun releases to the earth actually reaches the ground. About a third is reflected directly back into space by the atmosphere. The time in which solar energy is available, is also the time we least need it least - daytime. Because the sun's energy cannot be stored for use another time, we need to convert the suns energy into an energy that can be stored. One possible method of storing solar energy is by heating water that can be insulated. The water is heated by passing it through hollow panels. Black-coated steal plates are used because dark colours absorb heat more efficiently. However this method only supplies enough energy for activities such as washing and bathing. The solar panels generate "low grade" heat, that is, they generate low temperatures for the amount of heat needed in a day. In order to generate "high grade" heat, intense enough to convert water into high-pressure steam which can then be used to turn electric generators there must be another method. The concentrated beams of sunlight are collected in a device called a solar furnace, which acts on the same principles as a large magnifying glass. The solar furnace takes the sunlight from a large area and by the use of lenses and mirrors can focus the light into a very small area. Very elaborate solar furnaces have machines that angle the mirrors and lenses to the sun all day. This system can provide sizeable amounts of electricity and create extremely high temperatures of over 6000 degrees Fahrenheit. Solar energy generators are very clean, little waste is emitted from the generators into the environment. The use of coal, oil and gasoline is a constant drain, economically and environmentally. Will solar energy be the wave of the future? Could the worlds requirement of energy be fulfilled by the "powerhouse" of our galaxy - the sun? Automobiles in the future will probably run on solar energy, and houses will have solar heaters.

Solar Cells

Solar cells

Solar cells today are mostly made of silicon, one of the
most common elements on Earth. The crystalline silicon solar
cell was one of the first types to be developed and it is still
the most common type in use today. They do not pollute the
atmosphere and they leave behind no harmful waste products.
Photovoltaic cells work effectively even in cloudy weather and
unlike solar heaters, are more efficient at low temperatures.
They do their job silently and there are no moving parts to wear
out. It is no wonder that one marvels on how such a device would
function.
To understand how a solar cell works, it is necessary to go
back to some basic atomic concepts. In the simplest model of the
atom, electrons orbit a central nucleus, composed of protons and
neutrons. each electron carries one negative charge and each
proton one positive charge. Neutrons carry no charge. Every atom
has the same number of electrons as there are protons, so, on the
whole, it is electrically neutral. The electrons have discrete
kinetic energy levels, which increase with the orbital radius.
When atoms bond together to form a solid, the electron energy
levels merge into bands. In electrical conductors, these bands
are continuous but in insulators and semiconductors there is an
"energy gap", in which no electron orbits can exist, between the
inner valence band and outer conduction band [Book 1]. Valence
electrons help to bind together the atoms in a solid by orbiting
2 adjacent nucleii, while conduction electrons, being less
closely bound to the nucleii, are free to move in response to an
applied voltage or electric field. The fewer conduction electrons
there are, the higher the electrical resistivity of the material.
In semiconductors, the materials from which solar sells are
made, the energy gap Eg is fairly small. Because of this,
electrons in the valence band can easily be made to jump to the
conduction band by the injection of energy, either in the form of
heat or light [Book 4]. This explains why the high resistivity of
semiconductors decreases as the temperature is raised or the
material illuminated. The excitation of valence electrons to the
conduction band is best accomplished when the semiconductor is in
the crystalline state, i.e. when the atoms are arranged in a
precise geometrical formation or "lattice".
At room temperature and low illumination, pure or so-called
"intrinsic" semiconductors have a high resistivity. But the
resistivity can be greatly reduced by "doping", i.e. introducing
a very small amount of impurity, of the order of one in a million
atoms. There are 2 kinds of dopant. Those which have more valence
electrons that the semiconductor itself are called "donors" and
those which have fewer are termed "acceptors" [Book 2].
In a silicon crystal, each atom has 4 valence electrons,
which are shared with a neighbouring atom to form a stable
tetrahedral structure. Phosphorus, which has 5 valence electrons,
is a donor and causes extra electrons to appear in the conduction
band. Silicon so doped is called "n-type" [Book 5]. On the other
hand, boron, with a valence of 3, is an acceptor, leaving so-
called "holes" in the lattice, which act like positive charges
and render the silicon "p-type"[Book 5]. The drawings in Figure
1.2 are 2-dimensional representations of n-and p-type silicon
crystals, in which the atomic nucleii in the lattice are
indicated by circles and the bonding valence electrons are shown
as lines between the atoms. Holes, like electrons, will
remove under the influence of an applied voltage but, as the
mechanism of their movement is valence electron substitution from
atom to atom, they are less mobile than the free conduction
electrons [Book 2].
In a n-on-p crystalline silicon solar cell, a shadow
junction is formed by diffusing phosphorus into a boron-based
base. At the junction, conduction electrons from donor atoms in
the n-region diffuse into the p-region and combine with holes in
acceptor atoms, producing a layer of negatively-charged impurity
atoms. The opposite action also takes place, holes from acceptor
atoms in the p-region crossing into the n-region, combining with
electrons and producing positively-charged impurity atoms [Book
4]. The net result of these movements is the disappearance of
conduction electrons and holes from the vicinity of the junction
and the establishment there of a reverse electric field, which is
positive on the n-side and negative on the p-side. This reverse
field plays a vital part in the functioning of the device. The
area in which it is set up is called the "depletion area" or
"barrier layer"[Book 4].
When light falls on the front surface, photons with energy
in excess of the energy gap (1.1 eV in crystalline silicon)
interact with valence electrons and lift them to the conduction
band. This movement leaves behind holes, so each photon is said
to generate an "electron-hole pair" [Book 2]. In the crystalline
silicon, electron-hole generation takes place throughout the
thickness of the cell, in concentrations depending on the
irradiance and the spectral composition of the light. Photon
energy is inversely proportional to wavelength. The highly
energetic photons in the ultra-violet and blue part of the
spectrum are absorbed very near the surface, while the less
energetic longer wave photons in the red and infrared are
absorbed deeper in the crystal and further from the junction
[Book 4]. Most are absorbed within a thickness of 100 'm.
The electrons and holes diffuse through the crystal in an
effort to produce an even distribution. Some recombine after a
lifetime of the order of one millisecond, neutralizing their
charges and giving up energy in the form of heat. Others reach
the junction before their lifetime has expired. There they are
separated by the reverse field, the electrons being accelerated
towards the negative contact and the holes towards the positive
[Book 5]. If the cell is connected to a load, electrons will be
pushed from the negative contact through the load to the positive
contact, where they will recombine with holes. This constitutes
an electric current. In crystalline silicon cells, the current
generated by radiation of a particular spectral composition is
directly proportional to the irradiance [Book 2]. Some types of
solar cell, however, do not exhibit this linear relationship.
The silicon solar cell has many advantages such as high
reliability, photovoltaic power plants can be put up easily and
quickly, photovoltaic power plants are quite modular and can
respond to sudden changes in solar input which occur when clouds
pass by. However there are still some major problems with them.
They still cost too much for mass use and are relatively
inefficient with conversion efficiencies of 20% to 30%. With
time, both of these problems will be solved through mass
production and new technological advances in semiconductors.



Bibliography

1) Green, Martin Solar Cells, Operating Principles, Technology
and System Applications. New Jersey, Prentice-Hall, 1989. pg
104-106

2) Hovel, Howard Solar Cells, Semiconductors and Semimetals. New
York, Academic Press, 1990. pg 334-339

3) Newham, Michael ,"Photovoltaics, The Sunrise Industry", Solar
Energy, October 1, 1989, pp 253-256
4) Pulfrey, Donald Photovoltaic Power Generation. Oxford, Van
Norstrand Co., 1988. pg 56-61

5) Treble, Fredrick Generating Electricity from the Sun. New
York, Pergamon Press, 1991. pg 192-195

Reptiles

Essay on Reptiles

Reptiles are vertebrate, or backboned animals constituting the class
Reptilia and are characterized by a combination of features, none of which
alone could separate all reptiles from all other animals.
The characteristics of reptiles are numerous, therefore can not be
explained in great detail in this report. In no special order, the
characteristics of reptiles are: cold-bloodedness; the presence of lungs;
direct development, without larval forms as in amphibians; a dry skin with
scales but not feathers or hair; an amniote egg; internal fertilization; a
three or four-chambered heart; two aortic arches (blood vessels) carrying
blood from the heart to the body, unlike mammals and birds that only have
one; a metanephric kidney; twelve pairs of cranial nerves; and skeletal
features such as limbs with usually five clawed fingers or toes, at least
two spinal bones associated with the pelvis, a single ball-and-socket
connection at the head-neck joint instead of two, as in advanced amphibians
and mammals, and an incomplete or complete partition along the roof of the
mouth, separating the food and air passageways so that breathing can
continue while food is being chewed.
These and other traditional defining characteristics of reptiles have been
subjected to considerable modification in recent times. The extinct flying
reptiles, called pterosaurs or pterodactyls, are now thought to have been
warm-blooded and covered with hair. Also, the dinosaurs are also now
considered by many authorities to have been warm-blooded. The earliest
known bird, archaeopteryx, is now regarded by many to have been a small
dinosaur, despite its covering of feathers The extinct ancestors of the
mammals, the therapsids, or mammallike reptiles, are also believed to have
been warm-blooded and haired. Proposals have been made to reclassify the
pterosaurs, dinosaurs, and certain other groups out of the class Reptilia
into one or more classes of their own.
The class Reptilia is divided into 6 to 12 subclasses by different
authorities. This includes living and extinct species. In addition, a number
of these subclasses are completely extinct. The subclasses contain about 24
orders, but only 4 of these are still represented by living animals.
Of the living orders of reptiles, two arose earlier than the age of
reptiles, when dinosaurs were dominant. Tuataras, of the order
Rhynchocephalia, are found only on New Zealand islands, whereas the equally
ancient turtles, order Chelonia, occur nearly worldwide. The order
Crocodilia emerged along with the dinosaurs. Snakes and lizards, order
Squamata, are today the most numerous reptile species.
The Rhynchocephalia constitute the oldest order of living reptiles; the
only surviving representative of the group is the tuatara, or sphenodon
(Sphenodon punctatus). Structurally, the tuatara is not much different from
related forms, also assigned to the order Rhynchocephalia, that may have
appeared as early as the Lower Triassic Period (over 2 000 000 000 years
ago). The tuatara has two pairs of well-developed limbs, a strong tail, and
a scaly crest down the neck and back. The scales, which cover the entire
animal, vary in size. The tuatara also has a bony arch, low on the skull
behind the eye, that is not found in lizards. Finally, the teeth of the
tuatara are acrodont - i.e., attached to the rim of the jaw rather than
inserted in sockets.
Chelonia, another ancient order of reptiles, is chiefly characterised by a
shell that encloses the vital organs of the body and more or less protects
the head and limbs. The protective shell, to which the evolutionary success
of turtles is largely attributed, is a casing of bone covered by horny
shields. Plates of bone are fused with ribs, vertebrae, and elements of
shoulder and hip girdles. There are many shell variations and modifications
from family to family, some of them extreme. At its highest development, the
shell is not only surprisingly strong but also completely protective. The
lower shell (plastron) can be closed so snuggly against the upper (carapace)
that a thin knife blade could not be inserted between them.
A third order of the class Reptilia is Crocodilia. Crocodiles are generally
large, ponderous, amphibious animals, somewhat lizardlike in appearance, and
carnivorous. They have powerful jaws with conical teeth and short legs and
clawed, webbed toes. The tail is long and massive and the skin thick and
plated. Their snout is relatively long and varies considerably in
proportions and shape. The thick, large horny plates that cover most of the
body are generally arranged in a regular pattern. The form of the is adapted
to its amphibious way of life. Finally, the elongated body with its long,
muscular paddletail is well suited to rapid swimming.
The final living order of the class Reptilia is Squamata. Both snakes and
lizards are classified in this order, but lizards are separated into their
own suborder, Sauria. Lizards can be distinguished from snakes by the
presence of two pairs of legs, external ear openings, and movable eyelids,
but these convenient external diagnostic features, while absent in snakes,
are also absent in some lizards. Lizards can be precisely separated from
snakes, however, on the basis of certain internal characteristics. All
lizards have at least a vestige of a pectoral girdle (skeletal supports for
the front limbs) and sternum (breastbone). The lizard's brain is not
totally enclosed in a bony case but has a small region at the front covered
only by a membranous septum. The lizard's kidneys are positioned
symmetrically and to the rear; in snakes the kidneys are far forward, with
the right kidney placed farther front than the left. Finally, the lizard's
ribs are never forked, as are one or two pairs in the snake.
A natural classification of reptiles is more difficult than that of many
animals because the main evolution of the group was during Mesozoic time (a
time of transition in the history of life and in the evolution of the
Earth); 13 of 17 recognized orders are extinct. There is still little
agreement on reptile taxonomy among herpetologists and paleontologists.
Even the major categories of reptile classification are still in dispute. On
the other hand, there is general agreement that the base reptilian stock is
the Cotylosauria, which evolved from an amphibian labyrinthodont stock. It
is also quite clear that the coty losaurs early divided into two lines, one
of which (the pelycosaurs) represented the stock that gave rise to the
mammals. Another branch led to all of the other reptiles, and later, to the
birds as well. Thus, most of the questions of reptilian evolution and
classification deal with the reptiles' interrelationship, rather than with
their relationships with other animals.

Leonardo da Vinci (I wish)
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/ O O | I know it's cheap, but hey, I did it in 2 minutes!!!
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REPRODUCTION

====================================================================== REPRODUCTION: A-Courting to Nature! LIFE SCIENCES SIG ---------------------------------------------------------------------- For some time she had watched his movements, appearing coyly in his haunts. And now, had it paid off? Doubtless, he was in love. His muscles were taut; he swooped through the air more like an eagle than a Greylag gander. The only problem was, it was not for her that he then landed in a flurry of quacks and wingbeats, or for her that he dashed off surprise attacks on his fellows. It was, rather, for another - for her preening rival across the Bavarian lake. Poor goose. Will she mate with the gander of her dreams? Or will she trail him for years, laying infertile egg clutches as proof of her faithfulness? Either outcome is possible in an animal world marked daily by scenes of courtship, spurning and love triumphant. And take note: these are not the imaginings of some Disney screen-16 writer. Decades ago Konrad Lorenz, a famed Austrian naturalist, made detailed studies of Greylags and afterwards showed no hesitation in using words like love, grief and even embarrassment to describe the behavior of these large, social birds. At the same time he did not forget that all romance - animal and human - is tied intimately to natural selection. Natural selection brought on the evolution of males and females during prehistoric epochs when environmental change was making life difficult for single-sex species such as bacteria and algae. Generally, these reproduced by splitting into identical copies of themselves. New generations were thus no better than old ones at surviving in an altered world. With the emergence of the sexes, however, youngsters acquired the qualities of two parents. This meant that they were different from both - different and perhaps better at coping with tough problems of survival. At the same time, nature had to furnish a new set of instincts which would make "parents" out of such unreflective entities as mollusks and jellyfish.. The peacock's splendid feathers, the firefly's flash, the humpback whale's resounding bellow - all are means these animals have evolved to obey nature's command: "Find a mate. Transmit your characteristics through time!" But while most males would accept indiscriminate mating, females generally have more on their minds. In most species, after all, they take on reproduction's hardest chores such as carrying young, incubating eggs and tending newborns. Often they can produce only a few young in a lifetime. (Given half a chance, most males would spawn thousands.) So it's no surprising that the ladies are choosy. They want to match their characteristics with those of a successful mate. He may flap his wings or join a hockey team, but somehow he must show that his offspring will not likely be last to eat or first in predatory jaws. Strolling through the Australian underbrush that morning, she had seen nothing that might catch a female bowerbird's eye. True, several males along the way had built avenue bowers - twin rows of twigs lined up north and south. True, they had decorated their constructions with plant juices and charcoal. Yet they displayed nothing out front! Not a beetle's wing. Not a piece of flower. Then she saw him. He stood before the largest bower and in his mouth held a most beautiful object. It was a powder blue cigarette package, and beneath it there glinted a pair of pilfered car keys. Without hesitation she hopped forward to watch his ritual dance. Males have found many ways to prove their worth. Some, like bowerbirds, flaunt possessions and territory, defending these aggressively against the intrusion of fellow males. Others, like many birds and meat-eating mammals, pantomime nest building or otherwise demonstrate their capacity as dads. Still others, however, do nothing. Gentlemen may bring flowers, but most male fish just fertilize an egg pile some unknown female has left in underwater sand. For a fish, survival itself is a romantic feat. For other species, though, love demands supreme sacrifices. Shortly after alighting on the back of his mate, the male praying mantis probably had no idea what was in store. This would have been a good thing too, because as he continued to fertilize his partner's eggs, she twisted slowly around and bit off his head. She continued to put away his body parts until well nourished and thus more able to sustain her developing young. Luckily for most species, the urge to mate come on only occasionally, usually in springtime. For love can hurt, particularly if you intended has difficulty telling a mate from a meal. Pity the poor male of the spider species, Xysticus Cristatus, for instance. His only hope of survival is to tie a much larger female to the ground with silk thread, and keep her there. Every time a moth releases its attracting scent, or a bullfrog sings out its mating call, these animals are risking a blind date with some predator. Such alluring traits have long puzzled scientists, particularly those which seem not only risky but useless as well. Why, after all, should a frigate bird mate more if he puffs out an extra large red throat sac? How does ownership of such a thing indicate a superior individual? Until recently, the question stymied biologists, but then researchers in the U.S. and Sweden announced a possible answer. While studying widowbirds, among whom extravagant tail feathers are hip, they discovered that the longest-tailed males also carried a lower number of blood parasites. Sexual ornamentation seemed to be a means by which males could show of superfluous health and energy. All of which may bring us to fast sports cars, flashy clothes and other accessories of the human suitor. After all, if he can afford dinner at the city's most expensive restaurant, chances are he could finance a baby too.

Rasmussens Encephalitis

Keyur P.
Biology...Science
Rasmussen's Encephalitis


The human immune system is an amazing system that is constantly on the alert protecting us from
sicknesses. Thousands of white blood cells travel in our circulatory system destroying all foreign
substances that could cause harm to our body or to any of the millions of processes going on inside. Now
imagine a condition where this awesome system turns against the most complex organ in the human body,
the brain. Deadly as it is, this condition is known as Rasmussen's encephalitis.
The meaningful research on Rasmussen's encephalitis was begun (unintentionally) by Scott Rogers
and Lorise Gahring, two neurologists, who were at the time measuring the distribution of glutamate
receptors in the brain. Later on when more provocative information was found they enlisted the help of
James McNamara and Ian Andrews, epilepsy experts at Duke University Medical Center.
The details on Rasmussen's encephalitis were very bleak at the time when the men began their
research. All that was known is that Rasmussen's encephalitis was a degenerative disease of the brain
that caused seizures, hemiparesis, and dementia normally in the first ten years of life. The seizures that
were caused by Rasmussen's encephalitis were unstoppable by normal anti-seizure drugs used
conventionally. What the worst part of the disease was that the pathogenesis for it were not known and
even worse was how it developed.
The first clue was delivered when Rogers and Gahring were trying to register the distribution of the
glutamate receptors using antibodies, that tag on to the receptor itself. The proteins that make up the
glutamate receptors(GluR) are only found inside the blood brain barrier(BBB). Glutamate and a few
related amino acids are the dominant form of excitatory neurotransmitter in the central nervous system of
mammals. If one of these GluRs happens to wander into the actual bloodstream, that is outside the BBB,
it would be considered an outsider and destroyed immediately. So if these GluRs were put into the normal
blood stream then the immune system would produce antibodies which could then be used in the
searching for the glutamate receptors.
In order to test this theory the researchers injected the GluRs into the blood stream of a normal
healthy rabbit hoping to produce good results. At this point the experiment took a dramatic turn, after
receiving a few doses of the protein two of the three rabbits began to twitch, as though they were suffering
the pain of an epileptic seizure. Now the help of McNamara and Andrews was enlisted.
When McNamara and Andrews examined the brain tissue of the rabbits, they saw what seemed to be
a familiar inflammatory pattern, clumps of immune cells all around blood vessels. This description
exactly matched the description of persons suffering from Rasmussen's encephalitis, moreover something
as this would never be found in a healthy brain. A healthy brain has its blood capillaries enclosed in the
BBB membrane, so such a case as the one mentioned above would not be possible.
As protective as the BBB is, it can be breached by something like a head injury. What was
happening was that the antibodies which were out to get the GluR proteins were somehow finding a way
into the brain and directing an attack towards all GluR receptor proteins in the brain itself.
After some more examinations Rogers and McNamara decided that these attacks were the cause of
the seizures that are often experienced by sufferers of Ramussen's encephalitis. Then if the case is of
antibodies in the bloodstream, than sufferers of Ramussen's encephalitis should have them in their
bloodstream and healthy normal peoples shouldn't. When this was actually tested the results were
positive that Rasmussen sufferers did have these antibodies in their bloodstreams and healthy people did
not. These were not only the right kind of antibodies but, the very antibodies that caused the seizures in
people and rabbits. Thus when these antibodies were removed by plasma exchange(PEX) it caused a
temporary relief from the seizures but soon the body starts making more antibodies of the type and the
seizures start once again. After all the examinations two questions remained, why does the body mount
an immune response against one of its own brain proteins, and how do these antibodies get through the
BBB?
What is thought right now is that people get antibodies when they are infected by a microorganism
like a bacterium or a virus that is similar in structure to the GluR. When this happens the body mounts an
immune response against, and it just so happens that at this stage you suffer a blow to the head. This will
open your BBB to the antibodies and they will attack the friendly GluRs in the brain, causing seizures and
further opening your BBB to more antibodies.
Now a malicious rhythm begins: antibodies break through the BBB, inflammation is caused due to
the break in, seizures are now caused and BBB opens up further, further opening in the BBB cause more
seizures. The inflammation is caused by the autoimmune process against the GluR. All the seizures
occur where the initial break in the BBB happened due to a blow to the head, explaining why they
seizures are confined to just one hemisphere. The only problem with this theory is that the rabbits
developed seizures without ever being whacked on the head, but that also could be because a rabbit's brain
is not as well insulated as a human's.
Normally what happens to an individual is that after he or she is involved in this cycle the only
thing that can make for relief is the recurrent plasma exchange. This will only cease the seizures
temporarily, but they will start again when the body has made more new antibodies. After this has been
done many times the hemisphere in which sufferers of Ramussen's encephalitis is present will deteriorate
to the point where a hemispherectomy has to be performed. This will render the person to mental
disintegration where he or she has no more mental capacity and generally to the point of no return, death.
Rasmussen's encephalitis is a very deadly disease, but it is also a very rare disease, occurring in only
48 people between 1957 and 1987. As of now there are no FDA approved drugs for the sufferers of
Ramussen's encephalitis. Now the researchers are working on a drug that will block the activity of this
particular antibody, but this could lead to further problems. If this drug is being administered and a
bacteria or virus of a similar structure as the GluR is present the body would disregard it and this would
cause more health problems. After all this bad news all one can say is, "Good luck" to the ones suffering
from this living hell.




Atkins, "Rasmussen's encephalitis: nueroimaging findings in four patients." AJR-Am-J-
Roentgenol. June 1992.

Blume, "Rasmussen's chronic encephalitis in adults." Arch-Nuerol. March 1993.

Hanovar, "Rasmussen's encephalitis in surgery for epilepsy." Dev-Med-Child-Nuerol.
January 1992.

Leary, "Clues Found To Rare Form of Epilepsy." New York Times. December 5 1994,
pp. A4.

Whisenand, "Autoantibodies to glutamate receptor GluR3 in Rasmussen's encephalitis,"
Science. July 29 1994.

Prolonged Preservation of the Heart Prior to Transplantation

Biochemistry

Prolonged Preservation of the Heart Prior to Transplantation



Picture this. A man is involved in a severe car crash in
Florida which has left him brain-dead with no hope for any
kind of recovery. The majority of his vital organs are
still functional and the man has designated that his organs
be donated to a needy person upon his untimely death.
Meanwhile, upon checking with the donor registry board, it
is discovered that the best match for receiving the heart of
the Florida man is a male in Oregon who is in desperate need
of a heart transplant. Without the transplant, the man will
most certainly die within 48 hours. The second man's
tissues match up perfectly with the brain-dead man's in
Florida. This seems like an excellent opportunity for a
heart transplant. However, a transplant is currently not a
viable option for the Oregon man since he is separated by
such a vast geographic distance from the organ. Scientists
and doctors are currently only able to keep a donor heart
viable for four hours before the tissues become irreversibly
damaged. Because of this preservation restriction, the
donor heart is ultimately given to someone whose tissues do
not match up as well, so there is a greatly increased chance
for rejection of the organ by the recipient. As far as the
man in Oregon goes, he will probably not receive a donor
heart before his own expires.

Currently, when a heart is being prepared for
transplantation, it is simply submerged in an isotonic
saline ice bath in an attempt to stop all metabolic activity
of that heart. This cold submersion technique is adequate
for only four hours. However, if the heart is perfused with
the proper media, it can remain viable for up to 24 hours.
The technique of perfusion is based on intrinsically simple
principles. What occurs is a physician carefully excises
the heart from the donor. He then accurately trims the
vessels of the heart so they can be easily attached to the
perfusion apparatus. After trimming, a cannula is inserted
into the superior vena cava. Through this cannula, the
preservation media can be pumped in.

What if this scenario were different? What if doctors were
able to preserve the donor heart and keep it viable outside
the body for up to 24 hours instead of only four hours? If
this were possible, the heart in Florida could have been
transported across the country to Oregon where the perfect
recipient waited. The biochemical composition of the
preservation media for hearts during the transplant delay is
drastically important for prolonging the viability of the
organ. If a media can be developed that could preserve the
heart for longer periods of time, many lives could be saved
as a result.

Another benefit of this increase in time is that it would
allow doctors the time to better prepare themselves for the
lengthy operation. The accidents that render people
brain-dead often occur at night or in the early morning.
Presently, as soon as a donor organ becomes available,
doctors must immediately go to work at transplanting it.
This extremely intricate and intense operation takes a long
time to complete. If the transplanting doctor is exhausted
from working a long day, the increase in duration would
allow him enough time to get some much needed rest so he can
perform the operation under the best possible circumstances.

Experiments have been conducted that studied the effects of
preserving excised hearts by adding several compounds to the
media in which the organ is being stored. The most
successful of these compounds are pyruvate and a pyruvate
containing compound known as
perfluoroperhydrophenanthrene-egg yolk phospholipid
(APE-LM). It was determined that adding pyruvate to the
media improved postpreservation cardiac function while
adding glucose had little or no effect. To test the
function of these two intermediates, rabbit hearts were
excised and preserved for an average of 24.5 1 0.2 hours on
a preservation apparatus before they were transplanted back
into a recipient rabbit. While attached to the preservation
apparatus, samples of the media output of the heart were
taken every 2 hours and were assayed for their content. If
the compound in the media showed up in large amounts in the
assay, it could be concluded that the compound was not
metabolized by the heart. If little or none of the compound
placed in the media appeared in the assay, it could be
concluded that compound was used up by the heart metabolism.

The hearts that were given pyruvate in their media
completely consumed the available substrate and were able to
function at a nearly normal capacity once they were
transplanted. Correspondingly, hearts that were preserved
in a media that lacked pyruvate had a significantly lower
rate of contractile function once they were transplanted.
The superior preservation of the hearts with pyruvate most
likely resulted from the hearts use of pyruvate through the
citric acid cycle for the production of energy through
direct ATP synthesis (from the reaction of succinyl-CoA to
succinate via the enzyme succinyl CoA synthetase) as well
as through the production of NADH + H+ for use in the
electron transport chain to produce energy.

After providing a preservation media that contained
pyruvate, a better recovery of the heart tissue occurred.
Most of the pyruvate consumed during preservation was
probably oxidized by the myocardium in the citric acid
cycle. Only a small amount of excess lactate was detected
by the assays of the preservation media discharged by the
heart. The lactate represented only 15% of the pyruvate
consumed. If the major metabolic route taken by pyruvate
during preservation had been to form lactate dehydrogenase
for regeneration of NAD+ for continued anaerobic glycolysis,
rather than by the aerobic citric acid cycle (pyruvate
oxidation), then a higher ratio of excess lactate produced
to pyruvate consumed would have been observed.

Hearts given a glucose substrate did not transport or
consume that substrate, even when it was provided as the
sole exogenous substrate. It might be expected that glucose
would be used up in a manner similar to that of pyruvate.
This expectation is because glucose is a precursor to
pyruvate via the glycolytic pathway however, this was not
the case. It was theorized this lack of glucose use may
have been due to the fact that the hormone insulin was not
present in the media. Without insulin, one may think the
tissues of the heart would be unable to adequately take
glucose into their tissues in any measurable amount, but
this is not the case either. It is known that hearts
working under physiologic conditions do use glucose in the
absence of insulin, but glucose consumption in that
situation is directly related to the performance of work by
the heart, not the presence of insulin.

To further test the effects of the addition of insulin to
the glucose media, experiments were done in which the
hormone was included in the heart preservation media5-7.
Data from those studies does not provide evidence that the
hormone is essential to insure glucose use or to maintain
the metabolic status of the heart or to improve cardiac
recovery. In a hypothermic (80C) setting, insulin did not
exert a noticeable benefit to metabolism beyond that
provided by oxygen and glucose. This hypothermic setting is
analogous to the setting an actual heart would be in during
transportation before transplant.

Another study was done to determine whether the compound
perfluoroperhydrophenanthrene-egg yolk phospholipid,
(APE-LM) was an effective media for long-term hypothermic
heart preservation3. Two main factors make APE-LM an
effective preservation media. (1) It contains a lipid
emulsifier which enables it to solubilize lipids. From this
breakdown of lipids, ATP can be produced. (2) APE-LM
contains large amounts of pyruvate. As discussed earlier,
an abundance of energy is produced via the oxidation of
pyruvate through the citric acid cycle.

APE-LM-preserved hearts consumed a significantly higher
amount of oxygen than hearts preserved with other media.
The higher oxygen and pyruvate consumption in these hearts
indicated that the hearts had a greater metabolic oxidative
activity during preservation than the other hearts. The
higher oxidative activity may have been reflective of
greater tissue perfusion, especially in the coronary beds,
and thereby perfusion of oxygen to a greater percentage of
myocardial cells. Another factor contributing to the
effectiveness of APE-LM as a transplantation media is its
biologically compatible lipid emulsifier, which consists
primarily of phospholipids and cholesterol. The lipid
provides a favorable environment for myocardial membranes
and may prevent perfusion-related depletion of lipids from
cardiac membranes. The cholesterol contains a bulky steroid
nucleus with a hydroxyl group at one end and a flexible
hydrocarbon tail at the other end. The hydrocarbon tail of
the cholesterol is located in the non polar core of the
membrane bilayer. The hydroxyl group of cholesterol
hydrogen-bonds to a carbonyl oxygen atom of a phospholipid
head group. Through this structure, cholesterol prevents
the crystallization of fatty acyl chains by fitting between
them. Thus, cholesterol moderates the fluidity of
membranes.8

The reason there are currently such strict limits on the
amount of time a heart can remain viable out of the body is
because there must be a source of energy for the heart
tissue if it is to stay alive. Once the supply of energy
runs out, the tissue suffers irreversible damage and dies.
Therefore, this tissue cannot be used for transplantation.
If hypothermic hearts are not given exogenous substrates
that they can transport and consume, like pyruvate, then
they must rely on glycogen or lipid stores for energy
metabolism. The length of time that the heart can be
preserved in vitro is thus related to the length of time
before these stores become too low to maintain the required
energy production needs of the organ. It is also possible
that the tissue stores of ATP and phosphocreatine are
critical factors. It is known that the amount of ATP in
heart muscle tissues is sufficient to sustain contractile
activity of the muscle for less than one second. This is
why phosphocreatine is so important. Vertebrate muscle
tissue contains a reservoir of high-potential phosphoryl
groups in the form of phosphocreatine. Phosphocreatine can
transfer its phosphoryl group to ATP according to the
following reversible reaction:

phosphocreatine + ADP + H+ 9 ATP + creatine

Phosphocreatine is able to maintain a high concentration of
ATP during periods of muscular contraction. Therefore, if
no other energy producing processes are available for the
excised heart, it will only remain viable until its
phosphocreatine stores run out.


A major obstacle that must be overcome in order for heart
transplants to be successful, is the typically prolonged
delay involved in getting the organ from donor to recipient.
The biochemical composition of the preservation media for
hearts during the transplant and transportation delays are
extremely important for prolonging the viability of the
organ. It has been discovered that adding pyruvate, or
pyruvate containing compounds like APE-LM, to a preservation
medium greatly improves post-preservation cardiac function
of the heart. As was discussed, the pyruvate is able to
enter the citric acid cycle and produce sufficient amounts
of energy to sustain the heart after it has been excised
until it is transplanted.

Increasing the amount of time a heart can remain alive
outside of the body prior to transplantation from the
current four hours to 24 hours has many desirable benefits.
As discussed earlier, this increase in time would allow
doctors the ability to better match the tissues of the donor
with those of the recipient. Organ rejection by recipients
occurs frequently because their tissues do not suitably
match those of the donors. The increase in viability time
would also allow plenty of opportunity for the organ to be
transported to the needy person, even if it must go across
the country.

Ovarian Cancer

Of all gynecologic malignancies, ovarian cancer continues to have the
highest mortality and is the most difficult to diagnose. In the United States
female population, ovarian cancer ranks fifth in absolute mortality among
cancer related deaths (13,000/yr). In most reported cases, ovarian cancer,
when first diagnosed is in stages III or IV in about 60 to 70% of patients
which further complicates treatment of the disease (Barber, 3).

Early detection in ovarian cancer is hampered by the lack of appropriate
tumor markers and clinically, most patients fail to develop significant
symptoms until they reach advanced stage disease. The characteristics
of ovarian cancer have been studied in primary tumors and in established
ovarian tumor cell lines which provide a reproducible source of tumor material.
Among the major clinical problems of ovarian cancer, malignant progression,
rapid emergence of drug resistance, and associated cross-resistance remain
unresolved. Ovarian cancer has a high frequency of metastasis yet generally
remains localized within the peritoneal cavity. Tumor development has been
associated with aberrant, dysfunctional expression and/or mutation of
various genes. This can include oncogene overexpression, amplification or
mutation, aberrant tumor suppressor expression or mutation. Also, subversion
of host antitumor immune responses may play a role in the pathogenesis of
cancer (Sharp, 77).

Ovarian clear cell adenocarcinoma was first described by Peham in 1899 as
"hypernephroma of the ovary" because of its resemblance to renal cell carcinoma.
By 1939, Schiller noted a histologic similarity to mesonephric tubules and
classified these tumors as "mesonephromas." In 1944, Saphir and Lackner described
two cases of "hypernephroid carcinoma of the ovary" and proposed "clear cell"
adenocarcinoma as an alternative term. Clear cell tumors of the ovary are now
generally considered to be of mullerian and in the genital tract of mullerian origin.
A number of examples of clear cell adenocarcinoma have been reported to arise
from the epithelium of an endometriotic cyst (Yoonessi, 289). Occasionally, a renal
cell carcinoma metastasizes to the ovary and may be confused with a primary clear
cell adenocarcinoma.

Ovarian clear cell adenocarcinoma (OCCA) has been recognized as a distinct
histologic entity in the World Health Organization (WHO) classification of ovarian
tumors since 1973 and is the most lethal ovarian neoplasm with an overall five year
survival of only 34% (Kennedy, 342). Clear cell adenocarcinoma, like most ovarian
cancers, originates from the ovarian epithelium which is a single layer of cells found on
the surface of the ovary. Patients with ovarian clear cell adenocarcinoma are typically
above the age of 30 with a median of 54 which is similar to that of ovarian epithelial
cancer in general. OCCA represents approximately 6% of ovarian cancers and bilateral
ovarian involvement occurs in less that 50% of patients even in advanced cases.

The association of OCCA and endometriosis is well documented (De La Cuesta,
243). This was confirmed by Kennedy et al who encountered histologic or intraoperative
evidence of endometriosis in 45% of their study patients. Transformation
from endometriosis to clear cell adenocarcinoma has been previously demonstrated in
sporadic cases but was not observed by Kennedy et al. Hypercalcemia occurs in a
significant percentage of patients with OCCA. Patients with advanced disease are more
typically affected than patients with nonmetastatic disease. Patients with OCCA are also
more likely to have Stage I disease than are patients with ovarian epithelial cancer in
general (Kennedy, 348).

Histologic grade has been useful as an initial prognostic determinant in some studies
of epithelial cancers of the ovary. The grading of ovarian clear cell adenocarcinoma has
been problematic and is complicated by the multiplicity of histologic patterns found in
the same tumor. Similar problems have been found in attempted grading of clear cell
adenocarcinoma of the endometrium (Disaia, 176). Despite these problems, tumor
grading has been attempted but has failed to demonstrate prognostic significance.
However, collected data suggest that low mitotic activity and a predominance of clear
cells may be favorable histologic features (Piver, 136).

Risk factors for OCCA and ovarian cancer in general are much less clear than for
other genital tumors with general agreement on two risk factors: nulliparity and family
history. There is a higher frequency of carcinoma in unmarried women and in married
women with low parity. Gonadal dysgenesis in children is associated with a higher risk
of developing ovarian cancer while oral contraceptives are associated with a decreased
risk. Genetic and candidate host genes may be altered in susceptible families. Among
those currently under investigation is BRCA1 which has been associated with an
increased susceptibility to breast cancer. Approximately 30% of ovarian adenocarcinomas
express high levels of HER-2/neu oncogene which correlates with a poor prognosis
(Altcheck, 375-376). Mutations in host tumor suppresser gene p53 are found in 50% of
ovarian carcinomas. There also appears to be a racial predilection, as the vast majority
of cases are seen in Caucasians (Yoonessi, 295).

Considerable variation exists in the gross appearance of ovarian clear cell
adenocarcinomas and they are generally indistinguishable from other epithelial ovarian
carcinomas. They could be cystic, solid, soft, or rubbery, and may also contain
hemorrhagic and mucinous areas (O'Donnell, 250). Microscopically, clear cell
carcinomas are characterized by the presence of variable proportions of clear and hobnail
cells. The former contain abundant clear cytoplasm with often centrally located nuclei,
while the latter show clear or pink cytoplasm and bizarre basal nuclei with atypical
cytoplasmic intraluminal projections. The cellular arrangement may be tubulo acinar,
papillary, or solid, with the great majority displaying a mixture of these patterns. The
hobnail and clear cells predominate with tubular and solid forms, respectively (Barber,
214).

Clear cell adenocarcinoma tissue fixed with alcohol shows a high cytoplasmic
glycogen content which can be shown by means of special staining techniques.
Abundant extracellular and rare intracellular neutral mucin mixed with sulfate and
carboxyl group is usually present. The clear cells are recognized histochemically and
ultrastructurally (short and blunt microvilli, intercellular tight junctions and desmosomes,
free ribosomes, and lamellar endoplasmic reticulum). The ultrastructure of hobnail and
clear cells resemble those of the similar cells seen in clear cell carcinomas of the
remainder of the female genital tract (O'Brien, 254). A variation in patterns of histology
is seen among these tumors and frequently within the same one.

Whether both tubular components with hobnail cells and the solid part with clear cells
are required to establish a diagnosis or the presence of just one of the patterns is
sufficient has not been clearly established. Fortunately, most tumors exhibit a mixture of
these components. Benign and borderline counterparts of clear cell ovarian
adenocarcinomas are theoretical possibilities. Yoonessi et al reported that nodal
metastases could be found even when the disease appears to be grossly limited to the
pelvis (Yoonessi, 296). Examination of retroperitoneal nodes is essential to allow for
more factual staging and carefully planned adjuvant therapy.

Surgery remains the backbone of treatment and generally consists of removal of the
uterus, tubes and ovaries, possible partial omentectomy, and nodal biopsies. The
effectiveness and value of adjuvant radiotherapy and chemotherapy has not been clearly
demonstrated. Therefore, in patients with unilateral encapsulated lesions and
histologically proven uninvolvement of the contralateral ovary, omentum, and biopsied
nodes, a case can be made for (a)no adjuvant therapy after complete surgical removal
and (b) removal of only the diseased ovary in an occasional patient who may be young
and desirous of preserving her reproductive capacity (Altchek, 97). In the more adv-
anced stages, removal of the uterus, ovaries, omentum, and as much tumor as possible
followed by pelvic radiotherapy (if residual disease is limited to the pelvis) or
chemotherapy must be considered. The chemotherapeutic regimens generally involve
adriamycin, alkylating agents, and cisPlatinum containing combinations (Barber, 442).

OCCA is of epithelial origin and often contains mixtures of other epithelial tumors
such as serous, mucinous, and endometrioid. Clear cell adenocarcinoma is characterized
by large epithelial cells with abundant cytoplasm. Because these tumors sometimes
occur in association with endometriosis or endometrioid carcinoma of the ovary and
resemble clear cell carcinoma of the endometrium, they are now thought to be of
mullerian duct origin and variants of endometrioid adenocarcinoma. Clear cell tumors of
the ovary can be predominantly solid or cystic. In the solid neoplasm, the clear cells are
arranged in sheets or tubules. In the cystic form, the neoplastic cells line the spaces.
Five-year survival is approximately 50% when these tumors are confined to the ovaries,
but these tumors tend to be aggressive and spread beyond the ovary which tends to make
5-year survival highly unlikely (Altchek, 416).

Some debate continues as to whether clear cell or mesonephroid carcinoma is a
separate clinicopathological entity with its own distinctive biologic behavior and natural
history or a histologic variant of endometrioid carcinoma. In an effort to characterize
clear cell adenocarcinoma, Jenison et al compared these tumors to the most common of
the epithelial malignancies, the serous adenocarcinoma (SA). Histologically determined
endometriosis was strikingly more common among patients with OCCA than with SA.
Other observations by Jenison et al suggest that the biologic behavior of clear cell
adenocarcinoma differs from that of SA. They found Stage I tumors in 50% of the
observed patient population as well as a lower incidence of bilaterality in OCCA
(Jenison, 67-69). Additionally, it appears that OCCA is characteristically larger than
SA, possibly explaining the greater frequency of symptoms and signs at presentation.

Risk Factors
There is controversy regarding talc use causing ovarian cancer. Until recently, most
talc powders were contaminated with asbestos. Conceptually, talcum powder on the
perineum could reach the ovaries by absorption through the cervix or vagina. Since
talcum powders are no longer contaminated with asbestos, the risk is probably no longer
important (Barber, 200). The high fat content of whole milk, butter, and meat products
has been implicated with an increased risk for ovarian cancer in general.

The Centers for Disease Control compared 546 women with ovarian cancer to 4,228
controls and reported that for women 20 to 54 years of age, the use of oral
contraceptives reduced the risk of ovarian cancer by 40% and the risk of ovarian cancer
decreased as the duration of oral contraceptive use increased. Even the use of oral
contraceptives for three months decreased the risk. The protective effect of oral
contraceptives is to reduce the relative risk to 0.6 or to decrease the incidence of disease
by 40%. There is a decreased risk as high as 40% for women who have had four or
more children as compared to nulliparous women. There is an increase in the incidence
of ovarian cancer among nulliparous women and a decrease with increasing parity. The
"incessant ovulation theory" proposes that continuous ovulation causes repeated trauma
to the ovary leading to the development of ovarian cancer. Incidentally, having two or
more abortions compared to never having had an abortion decreases one's risk of
developing ovarian cancer by 30% (Coppleson, 25-28).

Etiology
It is commonly accepted that cancer results from a series of genetic alterations that
disrupt normal cellular growth and differentiation. It has been proposed that genetic
changes causing cancer occur in two categories of normal cellular genes, proto-
oncogenes and tumor suppressor genes. Genetic changes in proto-oncogenes facilitate
the transformation of a normal cell to a malignant cell by production of an altered or
overexpressed gene product. Such genetic changes include mutation, translocation, or
amplification of proto-oncogenes Tumor suppressor genes are proposed to prevent
cancer. Inactivation or loss of these genes contributes to development of cancer by the
lack of a functional gene product. This may require mutations in both alleles of a tumor
suppressor gene. These genes function as regulatory inhibitors of cell proliferation, such
as a DNA transcription factor, or a cell adhesion molecule. Loss of these functions
could result in abnormal cell division or gene expression, or increased ability of cells in
tissues to detach. Cancer such as OCCA most likely results from the dynamic interaction
of several genetically altered proto-oncogenes and tumor suppressor genes (Piver, 64-
67).

Until recently, there was little evidence that the origin of ovarian was genetic. Before
1970, familial ovarian cancer had been reported in only five families. A familial cancer
registry was established at Roswell Park Cancer Institute in 1981 to document the
number of cases occurring in the United States and to study the mode of inheritance. If
a genetic autosomal dominant transmission of the disease can be established, counseling
for prophylactic oophorectomy at an appropriate age may lead to a decrease in the death
rate from ovarian cancer in such families.

The registry at Roswell Park reported 201 cases of ovarian cancer in 94 families in
1984. From 1981 through 1991, 820 families and 2946 cases had been observed.
Familial ovarian cancer is not a rare occurrence and may account for 2 to 5% of all cases
of ovarian cancer. Three conditions that are associated with familial ovarian cancer are
(1) site specific, the most common form, which is restricted to ovarian cancer, and (2)
breast/ovarian cancer with clustering of ovarian and breast cases in extended pedigrees
(Altchek, 229-230). One characteristic of inherited ovarian cancer is that it occurs at a
significantly younger age than the non-inherited form.

Cytogenetic investigations of sporadic (non-inherited) ovarian tumors have revealed
frequent alterations of chromosomes 1,3,6, and 11. Many proto-oncogenes have been
mapped to these chromosomes, and deletions of segments of chromosomes (particularly
3p and 6q) in some tumors is consistent with a role for loss of tumor suppressor genes.
Recently, a genetic linkage study of familial breast/ovary cancer suggested linkage of
disease susceptibility with the RH blood group locus on chromosome 1p.

Allele loss involving chromosomes 3p and 6q as well as chromosomes 11p, 13q, and
17 have been frequently observed in ovarian cancers. Besides allele loss, point mutations
have been identified in the tumor suppressor gene p53 located on chromosome17p13.
Deletions of chromosome 17q have been reported in sporadic ovarian tumors suggesting
a general involvement of this region in ovarian tumor biology. Allelic loss of MYB and
ESR genes map on chromosome 6q near the provisional locus for FUCA2, the locus for
a-L-fucosidase in serum. Low activity of a-L-fucosidase in serum is more prevalent in
ovarian cancer patients. This suggests that deficiency of a-L-fucosidase activity in serum
may be a hereditary condition associated with increased risk for developing ovarian
cancer. This together with cytogenetic data of losses of 6q and the allelic losses at 6q
point to the potential importance of chromosome 6q in hereditary ovarian cancer
(Altchek, 208-212).

Activation of normal proto-oncogenes by either mutation, translocation, or gene
amplification to produce altered or overexpressed products is believed to play an
important role in the development of ovarian tumors. Activation of several proto-
oncogenes (particularly K-RAS, H-RAS, c-MYC, and HER-2/neu) occurs in ovarian
tumors. However, the significance remains to be determined. It is controversial as to
whether overexpression of the HER-2/neu gene in ovarian cancer is associated with poor
prognosis. In addition to studying proto-oncogenes in tumors, it may be beneficial to
investigate proto-oncogenes in germ-line DNA from members of families with histories
of ovarian cancer (Barber, 323-324). It is questionable whether inheritance or rare
alleles of the H-RAS proto-oncogene may be linked to susceptibility to ovarian cancers.

Diagnosis and Treatment
The early diagnosis of ovarian cancer is a matter of chance and not a triumph of
scientific approach. In most cases, the finding of a pelvic mass is the only available
method of diagnosis, with the exception of functioning tumors which may manifest
endocrine even with minimal ovarian enlargement. Symptomatology includes vague
abdominal discomfort, dyspepsia, increased flatulence, sense of bloating, particularly
after ingesting food, mild digestive disturbances, and pelvic unrest which may be present
for several months before diagnosis (Sharp, 161-163).

There are a great number of imaging techniques that are available. Ultrasounds,
particularly vaginal ultrasound, has increased the rate of pick-up of early lesions,
particularly when the color Doppler method is used. Unfortunately, vaginal sonography
and CA 125 have had an increasing number of false positive examinations. Pelvic
findings are often minimal and not helpful in making a diagnosis. However, combined
with a high index of suspicion, this may alert the physician to the diagnosis.

These pelvic signs include:
Mass in the ovarian area
Relative immobility due to fixation of adhesions
Irregularity of the tumor
Shotty consistency with increased firmness
Tumors in the cul-de-sac described as a handful of knuckles
Relative insensitivity of the mass
Increasing size under observation
Bilaterality (70% for ovarian carcinoma versus 5% for benign cases) (Barber, 136)

Tumor markers have been particularly useful in monitoring treatment, however, the
markers have and will probably always have a disadvantage in identifying an early
tumor. To date, only two, human gonadotropin (HCG) and alpha fetoprotein, are
known to be sensitive and specific. The problem with tumor markers as a means of
making a diagnosis is that a tumor marker is developed from a certain volume of tumor.
By that time it is no longer an early but rather a biologically late tumor (Altchek, 292).

Many reports have described murine monoclonal antibodies (MAbs) as potential tools
for diagnosing malignant ovarian tumors. Yamada et al attempted to develop a MAb
that can differentiate cells with early malignant change from adjacent benign tumor cells
in cases of borderline malignancy. They developed MAb 12C3 by immunizing mice with
a cell line derived from a human ovarian tumor. The antibody reacted with human
ovarian carcinomas rather than with germ cell tumors. MAb 12C3 stained 67.7% of
ovarian epithelial malignancies, but exhibited an extremely low reactivity with other
malignancies. MAb 12C3 detected a novel antigen whose distribution in normal tissue is
restricted. According to Yamada et al, MAb 12C3 will serve as a powerful new tool for
the histologic detection of early malignant changes in borderline epithelial neoplasms.
MAb 12C3 may also be useful as a targeting agent for cancer chemotherapy (Yamada,
293-294).

Currently there are several serum markers that are available to help make a diagnosis.
These include CA 125, CEA, DNB/70K, LASA-P, and serum inhibin. Recently the
urinary gonadotropin peptide (UCP) and the collagen-stimulating factor have been
added. Although the tumor markers have a low specificity and sensitivity, they are often
used in screening for ovarian cancer. A new tumor marker CA125-2 has greater
specificity than CA125. In general, tumor markers have a very limited role in screening
for ovarian cancer.

The common epithelial cancer of the ovary is unique in killing the patient while being,
in the vast majority of the cases, enclosed in the anatomical area where it initially
developed: the peritoneal cavity. Even with early localized cancer, lymph node
metastases are not rare in the pelvic or aortic areas. In most of the cases, death is due to
intraperitoneal proliferation, ascites, protein loss and cachexia. The concept of
debulking or cytoreductive surgery is currently the dominant concept in treatment.

The first goal in debulking surgery is inhibition of debulking surgery is inhibition of
the vicious cycle of malnutrition, nausea, vomiting, and dyspepsia commonly found in
patients with mid to advanced stage disease. Cytoreductive surgery enhances the
efficiency of chemotherapy as the survival curve of the patients whose largest residual
mass size was, after surgery, below the 1.5 cm limit is the same as the curve of the
patients whose largest metastatic lesions were below the 1.5 cm limit at the outset
(Altchek, 422-424).

The aggressiveness of the debulking surgery is a key question surgeons must face
when treating ovarian cancers. The debulking of very large metastatic masses makes no
sense from the oncologic perspective. As for extrapelvic masses the debulking, even if
more acceptable, remains full of danger and exposes the patient to a heavy handicap.
For these reasons the extra-genital resections have to be limited to lymphadenectomy,
omentectomy, pelvic abdominal peritoneal resections and rectosigmoid junction
resection. That means that stages IIB and IIC and stages IIIA and IIB are the only true
indications for extrapelvic cytoreductive surgery. Colectomy, ileectomy, splenectomy,
segmental hepatectomy are only exceptionally indicated if they allow one to perform a
real optimal resection. The standard cytoreductive surgery is the total hysterectomy with
bilateral salpingoophorectomy. This surgery may be done with aortic and pelvic lymph
node sampling, omentectomy, and, if necessary, resection of the rectosigmoidal junction
(Barber. 182-183).

The concept of administering drugs directly into the peritoneal cavity as therapy of
ovarian cancer was attempted more than three decades ago. However, it has only been
within the last ten years that a firm basis for this method of drug delivery has become
established. The essential goal is to expose the tumor to higher concentrations of drug
for longer periods of time than is possible with systemic drug delivery. Several agents
have been examined for their efficacy, safety and pharmacokinetic advantage when
administered via the peritoneal route.

Cisplatin has undergone the most extensive evaluation for regional delivery. Cisplatin
reaches the systemic compartment in significant concentrations when it is administered
intraperitoneally. The dose limiting toxicity of intraperitoneally administered cisplatin is
nephrotoxicity, neurotoxicity and emesis. The depth of penetration of cisplatin into the
peritoneal lining and tumor following regional delivery is only 1 to 2 mm from the
surface which limits its efficacy. Thus, the only patients with ovarian cancer who would
likely benefit would be those with very small residual tumor volumes. Overall,
approximately 30 to 40% of patients with small volume residual ovarian cancer have
been shown to demonstrate an objective clinical response to cisplatin-based locally
administered therapy with 20 to 30% of patients achieving a surgically documented
complete response. As a general rule, patients whose tumors have demonstrated an
inherent resistance to cisplatin following systemic therapy are not considered for
treatment with platinum-based intraperitoneal therapy (Altchek, 444-446).

In patients with small volume residual disease at the time of second look laparotomy,
who have demonstrated inherent resistance to platinum-based regimens, alternative
intraperitoneal treatment programs can be considered. Other agents include
mitoxantrone, and recombinant alpha-interpheron. Intraperitoneal mitoxanthone has
been shown to have definite activity in small volume residual platinum-refractory ovarian
cancer. Unfortunately, the dose limiting toxicity of the agent is abdominal pain and
adhesion formation, possibly leading to bowel obstruction. Recent data suggests the
local toxicity of mitoxanthone can be decreased considerably by delivering the agent in
microdoses.

Ovarian tumors may have either intrinsic or acquired drug resistance. Many
mechanisms of drug resistance have been described. Expression of the MDR1 gene that
encodes the drug efflux protein known as p-glycoprotein, has been shown to confer the
characteristic multi-drug resistance to clones of some cancers. The most widely
considered definition of platinum response is response to first-line platinum treatment
and disease free interval. Primary platinum resistance may be defined as any progression
on treatment. Secondary platinum resistance is the absence of progression on primary
platinum-based therapy but progression at the time of platinum retreatment for relapse
(Sharp, 205-207).

Second-line chemotherapy for recurrent ovarian cancer is dependent on preferences of
both the patient and physician. Retreatment with platinum therapy appears to offer
significant opportunity for clinical response and palliation but relatively little hope for
long-term cure. Paclitaxel (trade name: Taxol), a prototype of the taxanes, is cytotoxic
to ovarian cancer. Approximately 20% of platinum failures respond to standard doses of
paclitaxel. Studies are in progress of dose intensification and intraperitoneal
administration (Barber, 227-228). This class of drugs is now thought to represent an
active addition to the platinum analogs, either as primary therapy, in combination with
platinum, or as salvage therapy after failure of platinum.

In advanced stages, there is suggestive evidence of partial responsiveness of OCCA to
radiation as well as cchemotherapy, adriamycin, cytoxan, and cisPlatinum-containing
combinations (Yoonessi, 295). Radiation techniques include intraperitoneal radioactive
gold or chromium phosphate and external beam therapy to the abdomen and pelvis. The
role of radiation therapy in treatment of ovarian canver has diminished in prominence as
the spread pattern of ovarian cancer and the normal tissue bed involved in the treatment
of this neoplasm make effective radiation therapy difficult. When the residual disease
after laparotomy is bulky, radiation therapy is particularly ineffective. If postoperative
radiation is prescribed for a patient, it is important that theentire abdomen and pelvis are
optimally treated to elicit a response from the tumor (Sharp, 278-280).

In the last few decades, the aggressive attempt to optimize the treatment of
ovarian clear cell adenocarcinoma and ovarian cancer in general has seen remarkable
improvements in the response rates of patients with advanced stage cancer without
dramatically improving long-term survival. The promises of new drugs with activity
when platinum agents fail is encouraging and fosters hope that, in the decades to come,
the endeavors of surgical and pharmacoogical research will make ovarian cancer an
easily treatable disease.




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Organism Adaptation

Organism Adaptation 5-4-1993 1)stimulus: a change in the environment that necessities a response, or adjustment by an organism (ex. swirling dust) response: the adjustment or change you make to a stimulus (ex. blinking your eyes) 2)Protists respond to a negative stimuli by moving away from it. Protists respond to: light, irritating chemicals, temperature, touch, etc. 3)Yes, they grow towards the stimulus (ex. light). photoropism: it means the organism grows towards the light. no geotropism: it means the organism grows towards the ground. no 4)This is because animals have the most highly developed sensory systems of all organisms. 5)Three factors that affect an organism's response are the type, number, and complexity of an animal's sense organs. The way they affect the response is determined by the type, number, and complexity of the animal's sense organs. 6)positive: food, money negative: a man pointing a gun at you neutral: sound of traffic 7)In general, organisms go towards positive stimuli, and go away from negative one. 8)voluntary: eating a bowl of hot chicken soup involuntary: watering of your mouth learned: talking 9)When an animal receives a scare, it can either Fight, Flight (go away from), Freeze the/from organism that is scaring that animal. The animal releases adrenaline that gives it the strength to do one of those things. pg. 136 #3,4,challenger) 3)automatic: i)blinking your eyes when dust gets in them ii)mouth waters when you smell food iii)moving your hand away when it gets burned voluntary: i)eat a bowl of soup ii)drink water iii)watching TV 4)The stimulus. You need the stimulus to make a response. b)No, it is not possible. This is because with an action, there is a reaction. No, you need a stimuli to make a response, otherwise it is not really a response. 5)i)it comes out of the ground ii)it crows iii)it barks and chases the perpetrator iv)it chases and eats a gazelle b)i)the flooding of its home ii)getting light iii)the person breaking in iv)its hunger Challenger It helps to keep the brain and heart from freezing. pg. 146 #1-5) 1)i)taste ii)touch iii)sight iv)smell v)hearing 2)The protists can only sense chemical. 3)This effect is called sensory adaptation. b)An advantage is that you aren't bothered by the smell. A disadvantage is if you are accustomed to the smell of smoke, the smell of smoke might not alert you if your house is on fire. b)cone: when it is light out rod: when it is dark out c)They aren't as developed as some other organisms. 5)Eyelid: this is because your hell cells are very tough from being walked on. This causes them not to be very sensitive. 5-6-1993 pg.13 #1-6) 1)environment: everything in an organism's surroundings biotic environment: all living things in an environment abiotic environment: non living things in an environment 2)When you breathe, your body extracts oxygen from the air. b) large animal eats smaller animal smaller animals larger animal dies and eats plants fertilizes ground soil grows plants 3)biology,ecology: they are the study of things on earth; ecology is the study of environment, biology is the study of animals b)producers,consumers: they live off the environment; pro. manufactures food, con. can't manufacture other food, but eat other organisms c)scavenger,decomposer: both live of off dead organisms; decom. break down the bodies of dead organisms d)habitat,niche: have to do with were an animal lives hab.=enviro. space were an organism lives, niche = way an organism reacts with its environment e)environment,ecosystem: were organisms live; enviro.= everything in an organism's surroundings, eco.= were organisms of a distinct group interact 4)a)auto b)hetro c) auto d)auto e)auto f)hetro 5)biosphere: layer of planet where living things exist and interact b)lithosphere: solid portion of the Earth's surface c)hydrosphere: layer of water that covers nearly 3/4 of the Earth's surface d)atmosphere: mass of air surrounding the Earth 6)The scavengers come and totally eat the carcass. The decomposers decompose the carcass and it fertilizes the ditch. pg. 18 #1-6) 1)herbivore: animals that consume only plant material (ex. cattle, sheep) trophic level: how directly a consumer interacts with the producers of its ecosystem food chain: a feeding sequence in which each kind of organism eats the one below it in the chain (ex. grass -> mouse -> wolf) 2)Because the producer provides the food for the consumers. 3)Herbivores, this is because you need the herbivores to feed the carnivores, and if there aren't enough herbivores, the carnivores will die out. b)Producers, this is because the producers feed the consumers, and consumers will die if there is not enough producers. 4)omnivores,carnivore: they both eat animals; omnivores also eat plants b)primary,tertiary: they both eat other organisms; primary eats at the first level, and tertiary eats at the third level c)food chain,food web: they describe feeding sequences; food chain goes from one level to the next, web is interconnecting 6)There are six food chains. There are more because the three overlap each other. b)grain, grass, berries c)deer, mouse, grasshopper, rabbit d)hawk, snake, owl, wolf wolf is the top carnivore pg.36 #1-8) 1)environment: everything in an organism's surroundings environmental interaction: interaction within the environment for food and shelter b)They relate to ecology because the purpose of ecology is to study the environment and environmental interaction. 2)pond water: abiotic: pond water is not alive b)plant seeds: biotic: seeds are alive because they have the c)ability to grow d)fossils: abiotic: this is because fossils are fossilized bones of e)dead animals f)soil: abiotic: soil is not alive g)soil organisms: biotic: this is because all organisms are living 3)autotroph heterotroph grass grasshopper, salmon seaweed grass snake, starfish b)producer consumer grass grasshopper, salmon seaweed grass snake, starfish c)The autotrophs were also the producers, and the heterotrophs were also the consumers. 4)Decomposers are the heterotrophs because they feed off of dead organisms and organism waste. b)Scavengers are consumers because they feed off of dead organisms. c)Because the scavengers and decomposers get rid of the waste and dead organisms. 5)A dead organism is a part of the abiotic environment because it no longer has life in it. b)First, scavengers come and eat the meat of the dead organism, then a decomposer carries out chemical decomposition. Large, complex molecules of living things are broken down to smaller, simpler molecules. c)If the corpses were indestructible, our roads and yards would be carpeted with dead bodies. 6)habitat: the environmental space in which an organism lives niche: all the ways in which an organism interacts with its biotic and abiotic environments b)Grass, plants, and a bison occupy different niches in the same habitat. 7The layer of our planet where living things exist and interact. b)lithosphere: solid portion of the Earth (ex. rocks) hydrosphere: the water portion of the Earth (ex. sea) atmosphere: the air surrounding the Earth (ex. air) c)The zones are different sections were many organisms live, but the ecosystem is a unit of the biosphere in which organisms forming a distinct group interact with each other and with their environment. 8)ecosystem: a unit of the biosphere in which organisms forming a distinct group interact with each other and with their environment (ex. pond) b)Because green plants feed the other organisms in one way or another. c)There would be more plants because they are used to feeding the other animals. 5-13-1993 Senses Sight: photoreception - cones and rods - location? - function? Hearing: effects of vibrations in the ear? - choclea? - mechanoreception? Smell: olfaction? - chemoreception? - location of receptors Taste: location of chemoreceptors - categories or types - how do we taste spicy food Touch: location of receptors (3 different types) - varying ability - does one receptor in the skin respond to all types of touch, pressure, and pain? Sight photoreception: direction of light by sensory cells cones: specialized eye cells for bright light and color reception rods: specialized eye cells for vision at low light levels Rods and cones are located on the retina. Hearing The effects of vibrations in the ear is that the vibrations travel through a series of small bones into a coiled, fluid-filled cone. The vibrating fluid moves the hair cells, nerve impulses are sent to the brain where they are interpreted as sound. cochlea: a fluid-filled cone that helps detect sound mechanoreception: the ability to detect motion Smell olfaction: the sense of smell chemoreception: the ability to detect chemical stimuli The olfactory receptors are located high in the nasal cavity in a human Taste The receptors are located in taste buds situated in crevices in the tongue, in humans. Human taste receptors are limited to just four categories: sweet, salty, sour, and bitter. You taste spicy foods from the interaction of your sense of smell with these four basic taste. Touch In humans, touch receptors are located in the skin. The three types are Meissner's corpuscles, Pacinian corpuscles, Ruffini corpuscles. There is a variety of touch receptors. They can sense heat, cold, pain, touch, pressure. The ability of touch is different between people. No, different receptors respond to different types of touch, pressure, and pain. Sensory Systems in other Organisms - protists often respond by eating or avoiding like a baby - Euglena have a pigment spot -> sensitive to light - sense organs in organisms can be different from those in humans e.g. dogs, bats, dolphins respond to higher sound frequencies e.g. birds of prey (ex. hawk) have a better sense of vision e.g. insects have a better sense of smell Coordinating Responses: Movement and Location 3 steps to sense and response: 1) sensory receptors 2) Organisms must be able to respond ex. move away 3) a coordinated system that links sensing and responding -> this is called nervous system 5-14-1993 Nervous System - simplest nervous system is found in an organism called the Hydra, a fresh water jelly fish - when the Hydra is touched, it contracts - sensory cells in the Hydra relay the message to neurons that carry the message to muscle cells - in complex animals, groups of neurons from nerves and sensory cells are grouped together to form sensory organs - the central nervous system consists of a nerve chord and a brain - Ganglia are clumps of nerve cells that coordinate nerve signals in different parts of the body Three Types of Neurons 1) Sensory neurons: carry signals from the sense receptors 2) motor neurons: carry signals to parts of the body (ex. muscle, glands) 3) inter neurons: connect sensory neurons to motor neurons When your hand touches a hot kettle, heat receptors in your fingertips detect this. -> sends the message to receptors in your arm -> brain and spinal chord's inter neurons -> motor neurons -> arm muscles Movement and Locomotion - for protists and animals, responses usually involves some form of movement - all animals are capable of some sort of movement - an animal's movement is controlled by its nervous system locomotion: movement from one location to another - Most animals have some form of locomotion. Locomotion can be difficult to study because some animals move very quickly Nervous and Locomotory Systems of the Earthworm - earthworms respond to light, touch, moisture, and chemicals - sense receptors are located under the skin - central nervous systems of the earthworm is a double spinal chord - nerve chord is connected to two larger ganglia in the worm's head - this is the brain - there are smaller ganglia for each segment of the worm's body 5-18-1993 Nervous and Locomotory systems of the Earthworm - continued - Part II - the ganglia enables the earthworm to move each segment independently - earthworm also has 2 sets of muscles -one perpendicular to the other -1) longitudinal muscles: when contracted, the worm becomes shorter and fatter -2) circular muscles: when contracted, the worm becomes thinner and longer - when the worm is moving forward, you can see a wave of motion passing along the body of the worm 5-19-1993 Locomotion in other Organisms - different types of locomotion: running, swimming, gliding, jumping, hopping, crawling or pseudopodia (false feet) amoeba - animals have different body parts that aid in locomotion -e.g. spider monkey - tail, kangaroo - hind legs, bat - wings Sensory Systems of Other Organisms Protists: have chemoreceptors in cell membrane - these receptors can also detect the presence of other organisms Euglena: have a pigment spot: sensitive to light - Euglena can't see, but it will move towards the light - when there is enough light, the Euglena will perform photosynthesis - different organisms possess sense organs that are more sensitive than those of humans e.g. dogs and bats can detect sounds of higher frequencies birds of prey have a more sensitive sense of vision insects have a more sensitive sense of smell Photosynthesis sunlight + H2O + CO2 -> glucose + O2 energy + H2O + CO2 <- glucose + O2 Altering and Adapting to the External Environment - adaptations: features and behaviors that enable an organism to suit or fit its environment e.g. musk oxen of the Canadian Arctic: form protective circle, strong grinding teeth, long digestive tube, thick hairy coat - the environment can alter an organism, and the organism can also alter the environment Exchanging Materials with the Environment - living organisms absorb oxygen and eliminate carbon dioxide - land dwellers and aquatic organisms will exchange gasses with their surroundings - land vertebrates have lungs: open sacs inside the body, connected to the outside by a tube - aquatic vertebrate exchange gasses through their gills - as water flows over the gills, dissolved oxygen diffuses into the fish's bloodstream, and carbon dioxide diffuses out - insects have a system of air tubes called the trachea extending throughout their abdomen. these trachea are connected to spiracles (tiny breathing holes) on the body of the insect - warm-blooded species consume more oxygen than cold-blooded organisms - babies breathe much faster than adult humans - your breathing slows down when you are asleep - hibernating animals breathe very slowly How Gas Exchange Alters the Environment - cell respiration occurs in human cells: oxygen + sugar -> carbon dioxide + water + energy - oxygen is supplied by green plants undergoing photosynthesis carbon dioxide + water + light -> sugar + oxygen Exchanging Other Materials: Elimination and Excretion - gases are not the only things exchanged with the environment - animals also release liquid and solid wastes into the environment - these are acted upon by micro-organisms such as bacteria that recycle these waste products by using the materials for their own life process - if too man animals congregate in one spot, their waste production may exceed the recycling capacity of the decomposers - in Peru and California, bird droppings are harvested pg.168 #1-5) 1)gas exchange: inside the animal's body, oxygen from the external environment is exchanged for the waste gas, carbon dioxide 2)gills - fish lungs - human trachea - grasshopper b)fish - under water human - everywhere on land grasshopper - in grassy fields and lawns 3)The amount of oxygen required by an organism is determined by its size, if its asleep or not, and if its warm or cold blooded. 4)Respiration removes oxygen molecules from the air and replaces them with carbon dioxide molecules or vice versa. b)They are cellular respiration and photosynthesis. c)This is because one uses liquid and solid waste materials in the form of urine, feces, and sweat. They are released by excretion and elimination. 5-20-1993 Altering the Environment - every organism alters its environment simply by living in it - the impact of human activities on the environment is sometimes beneficial, but often has unforeseen circumstances - there has been an increase in atmospheric pollution, largely due to the burning of fossil fuels - fossil fuels increase the amount of sulfur dioxide, nitrogen dioxide, carbon dioxide, and carbon monoxide in the atmosphere - the amount of carbon dioxide present has increased by more than 30% in the past 100 years. This has produced the Greenhouse Effect. - Acid rain is caused by the mixing of sulfur and nitrogen oxides with water vapors. Greenhouse Effect - carbon from fossil fuels and the tropical rain forest combine with oxygen to produce CO2 - the danger results from global warming of the atmosphere - this may affect the ecosystems, and destroy some species which can't adapt to warmer conditions - Also, icebergs in the Arctic and Antarctic may melt causing coastal flooding - Since sunlight warms the Earth's surface more than the atmosphere, the surface transfers heat to the atmosphere. This heat is absorbed by gasses such as CO2 in the atmosphere. As the amount of the atmospheric CO2 rises, the amount of heat increases, thereby warming the atmosphere. How Humans Alter the Environment - humans can develop specialized dwelling (e.g. igloos). clothes (e.g. astronauts), and heating and cooling methods that enable them to survive in several different environments - humans can replace fields and forests with highways and cities - however, waste accumulation is a problem - how to dispose of garbage and non biodegradable materials How the Environment Alters Humans - there are several differences that make some body features better suited for a particular environment - people with a lot of skin pigment, and therefore darker skin, are protected from sunburns, and this is an advantage in hot areas - at higher altitudes, the environment oxygen levels are lower, and therefore, people with a higher density of oxygen carrying red blood cells are at an advantage, therefore, people living in higher altitudes tend to develop more red blood cells pg.184 #1-6) 1)They work as a group, they defend better as a group, and each member of the group has a specific job. 2)inherited variability: this means that you have inherited certain traits from your ancestors, but not everyone in your family has them 3)They can inherit structural and behavioral adaptation. b)duck: migration (behavioral), oily back (structural), fly in flocks (behavioral) polar bear: whit (structural), much fat (structural), padded feet (structural) camel: humps (structural), large feet (structural), low body fat (structural) 4)It needs other termites to help it feed, breed, and defend itself. 5)caribou: hibernate? geese: fly south for the winter maple trees: start storing food in its branches and not feeding its leaves 6) The knowledge an organism has can help it to live longer and better and to adapt better. 5-21-1993 - physiological adaptations are adjustments to environmental change involving a change in body chemistry - however, there are limits to how quickly the human body can alter in response to changes in the external environment - for example, people could never adopt to oxygen levels above 6000m Adapting to Environmental Change - when an organism becomes so specialized, and accustomed to a particular environment factor such as food, or climate then, change in this environmental factor may result in death of that species - insects are most adaptable organisms - some insects (cockroach) have survived almost 300mil. years unaltered - several factors responsible for insects power of survival 1)most insects undergo dramatic metamorphoses, as a result, juvenile and adult form eat different food, and survive in different conditions. If one food supply or environment was affected, it wouldn't destroy the entire population 2) insects also reproduce in very large numbers 3) short life span, therefore, many generations are produced in a short time, and mutations are quickly passed to the next generation. - if an individual possesses a characteristic that gives it an advantage in the environment, any offspring that inherit that characteristic may have a better chance of survival. After a few generations, the inherited characteristic could be more widespread in the population - peppered moth provides an example of process of adoption - before 1845, most peppered moths had light colored wings with dark markings - however, with industrialization and pollution, city dwellings became darkened from soot and smoke. The bark on trees also became darker. - now light color moth were at a disadvantage and its population deminished - pretty soon, dark color moths outnumbered light ones - a structural adoption is an inner physical feature that increases an organism's chance of survival e.g. curved talons of on a hawk 5-25-1993 - behavioral adaptations: certain actions that increase an organism's chance of survival - hibernation: state of deep sleep in which an organism can remain without food for weeks or months - before hibernating, the animal eats a lot to accumulate extra fat reserves - during hibernation, the breathing and heart rates slow down significantly - in spring, the hibernating animal wakes up - migration: animals moving to a different location due to an environmental/seasonal change - estivation: some desert animals become dormant in summer when water is scarce e.g. desert frogs, snakes, lizards Adapting Through Social Structure - social living arrangements make it easier for an animal to find a mate, find food, and avoid danger e.g. bee colony - consists of a queen bee, infertile female worker bees that hunt for food, feed the young, and protect the colony. There are also male bees called drones that solely act as breeder, and they do not work at all. No individual bee can survive on its own because its structural and behavioral adaptations are so specialized.