AIIMS AIPMT PMT Reference question and answers series

1.What is silent area in human brain?
Until recently, the prefrontal areas of human brain were referred to as the “silent areas” or “uncommitted cortex”, because injury to these regions was not accompanied by sensorimotor signs, and the function of these areas was not clear.
Prefrontal cortex or PFC, has long been known to endow qualities that differentiate human beings from all other animals. PFC was for some years, known to perform executive function, but now it has been demonstrated that its functions include the ability to organize behavioural response to solve a complex problem (including strategies used in learning information and searching memory). Moreover, it has been found to be involved in other behaviours such as moral judgement, appreciation of jokes, evaluating rewards, awareness, temperament, meditation, etc. Thus, far from being “silent”, “uncommitted” or known just for “psychial functions”, the PFC is comprised of a set of control systems, each with the separate target, i.e., different prefrontal areas control different activities that are separately localised.

2.How do transposons or jumping genes move?
Transposable elements or transposons are stretches of DNA that usually have repeated DNA segments at their ends and can jump within the genome, hence, are also known as jumping genes. They were discovered by Barbara Mc Clintock in corn plants (maize). She proposed that the kernel mosaics, which result from breaks at particular site at chromosome 9, were produced by the factor called Ds (for dissociation). However, this factor is incapable of inducing chromosome breakage by itself and requires another factor, Ac (for activator). Both Ac and Ds are members of a family of transposable elements. These elements are structurally related to each other and can insert at many different sites in chromosomes; hence also known as controlling elements. Transposase, a protein synthesised by Ac elements, is involved in transposition.
Genetic analysis has provided some information about the mechanism whereby Ac (and presumably Ds) elements transpose. Initially, the element is replicated by normal cellular machinery. Then one copy of Ac transposes ahead of the replication fork. When replication process is finished, there will be two sister chromatids, one with single copy of Ac (in the new location only) and one with two copies (one in new location and one in the old). The actual transposition of an Ac element is considered to be non-replicative because it is replicated during normal replication mechanism and not transposition.
Studies with diverse organisms, including bacteria, fungi, nematodes, insects, plants and mammals, suggest that transposable elements are widespread. These elements exhibit considerable variations in structure and function.

3. Glycolysis and Krebs’ cycle generate energy without oxygen, then what is the role of oxygen in aerobic respiration?

Aerobic respiration starts by breaking glucose down into pyruvate by glycolysis. Next, in a preparatory step for the Krebs’ cycle, coenzyme A joins to pyruvate causing a loss of one carbon and the generation of NADH. The acetyl CoA formed enters Krebs’ cycle and the acetyl group is transferred to a molecule of oxaloacetic acid making a molecule of citric acid which enters the cycle. The Krebs’ cycle releases CO2 and high energy molecules NADH and FADH2, which are converted into ATP by the mitochondrial electron transport chain (ETC). Oxygen acts the terminal electron acceptor in ETC. If there is no oxygen to accept electrons, the ETC stops working and NADH and FADH2 cannot be converted back into NAD and FAD; hence glucose biochemical pathway stops.
Moreover, substrate-level phosphorylation occurs during glycolysis and Krebs’ cycle and yields a relatively small amount of ATP. The generation of ATP from chemiosmosis at the end of ETC is called oxidative phosphorylation because when oxygen acts as terminal electron acceptor, there is a maximal amount of free energy released. Hence, more protons can be transported, which means that a greater charge buildup occurs across the inner mitochondrial membrane leading to synthesis of ATP. This process, thus, generates relatively large amount of ATP for the cell as compared to substrate – level phosphorylation.

4. Organs like liver and kidney are transplanted very often. Is it possible to transplant legs?
Yes, it is possible to transplant legs, however within the field of transplants, there are fewer vascularized composite transplants than other organ transplants performed every year. The area of vascularized composite allotransplantation comprises the vascularised transplantation of multiple tissues such as skin, muscle, bone, nerve and tendon as a functional unit.
Unlike the other organ transplants, leg transplants are little controversial mainly because of two reasons. Firstly, the prosthetic devices provide sufficient support successfully without the risk and complications of taking immuno-suppressive medications, and secondly, the sensation takes longer to return in case of transplanted leg which is not required in case of prostheses.
However, there are potential benefits of such transplantation which entail restoration of body image, recovery of sensation and its connection to the brain. Another advantage is the ability to perform daily activities which are not possible with prostheses. Following transplantation, medications such as immuno-suppressants are required to successfully prevent rejection of transplants. These do have sideeffects and people react differently to some drugs but ultimately the decision of transplantation needs addressing of the balance between the risks of immuno-suppression versus the benefits of receiving a quality of transplant.

5. How can we transplant a tissue or organ from an animal to human? What problems may arise in such a transplant?

Any procedure that involves the transplantation, implantation, or infusion into a human recipient of either live cells, tissues, or organs from a non-human animal source or human body fluids, cells, tissues or organs that have had ex-vivo contact with live non-human cells, tissues, or organs, is referred to as xenotransplantation.
In the light of the lack of supply of human organs for transplantation several alternatives including xenotransplantation have been investigated and debated. There are major issues with such a transplantation as transplanting solid organs from animal sources into humans results in rapid loss of xenograft because of hyperacute rejection. In this immunologic reaction, preformed antibodies (xenoreactive natural antibodies) circulating in human
blood bind to vascular epithelium of the animal organ and trigger a cascade that quickly results in thrombosis of the graft. If the transplanted organ is not rejected within minutes to hours, a more delayed type of immunologic response ultimately leads to thrombosis of the graft within hours to days. This process is known as delayed xenograft rejection or acute vascular rejection. The use of xenotransplantation products also carries a natural and expected risk of transmitting infectious pathogens, this is called xenosis.
A range of various approaches are investigated and proposed to circumvent xenograft rejection. Genetically engineered animals have been designed to downregulate expression of various immunogenic substances which constitute donor-based strategies. Secondly, there are recipient based strategies in which complement cascade can be interrupted therapeutically by using several inhibitory agents. Severe immune-modulating therapies have been developed to prolong xenograft survival. Because of xenosis, all major reports on xenotransplantation have recommended comprehensive monitoring and surveillance of xenograft recipient. Ethical, religious, and consensual matters are required be addressed for successful research in xenotransplantation.

6. What are stem cells? What is their role in human body?
Stem cells are undifferentiated cells in the body that can differentiate into specialised cells and can divide to produce more stem cells. In addition, they serve as internal repair system, dividing essentially to replenish other cells. In mammals, two broad types of stem cells have been identified, namely, embryonic stem cells, isolated from the inner cell mass of the blastocysts, and non-embryonic or adult stem cells which are found in various tissues. For adult stem cells there are three accessible sources: bone marrow, adipose tissue and blood. These can also be taken from umbilical cord blood just after the birth.
Stem cells are distinguished from other cell types by two important characteristics. First, they are able to differentiate into specialised cell types under certain physiologic or experimental conditions. Second, their ability to go through numerous cycles of cell division while maintaining the undifferentiated state. They are widely studied, for their potential therapeutic use. Researches made another break through by identifying conditions that would allow some specialised adult stem cells to be “reprogrammed” genetically to assume stem-cell like state. These are called induced pluripotent stem cells (iPSCs). Given its miraculous properties, medical research believe that stem cell therapy has the potential to dramatically revive treatment of many human diseases.

7. Why do autoimmune diseases occur more commonly in women?
Autoimmune diseases occur when the immune system begins attacking its own tissues rather than external pathogens. They affect ~8% of the population, 75- 78% of whom are women.
The basic immune response between men and women has been known to differ. Women produce a more vigorous immune response and increased antibody production. Sex hormones, such as estrogen, testosterone, and progesterone are believed to mediate many of the sex-based differences in the immune response and to account for sex differences in the prevalence of autoimmune diseases.
Recently, estrogen and androgens have been found to directly influence whether Th1 or Th2 type immune response develops by interacting with hormone receptors on immune cells. Moreover, cytokine receptors such as IL-1R, IL-18R have been discovered on hormone producing tissues which suggest bidirectional regulation of the immune response. Furthermore, proinflammatory cytokines such as TNF-a and IL-1b stimulate the release of glucocorticoids from the hypothalamus- pituitary -adrenal axis, which regulates the inflammatory process, along with increase in estrogens.
Generally, the occurrence of overt autoimmune disease, as opposed to the presence of autoimmune antibodies in the blood, depends on a balance between the incorrectly functioning systems, and the body’s ability to regulate them. It is possible that pregnancy and childbirth may leave women more susceptible to these conditions than men. It also seems that genetics play another important role in occurrence of autoimmune diseases.

8. Why do people die of drug overdose?
Drug overdose is ingestion or application of a drug or other substance in quantities greater than recommended. Every drug behaves differently in each person’s body and central nervous system, interacting with their unique body chemistry and underlying health conditions. For instance, a toxic dose of heroin increases the inhibitory effect of GABA (g-amino butyric acid), a neurotransmitter, which causes breathing to slow and eventually stop. Nicotine present in cigarettes can also kill by overdose. At high concentration, nicotine binds to receptors both in the brain and on muscles leading to paralysis of muscles that control breathing or to heart attack. Stimulants such as cocaine and methamphetamine trigger the release of norepinephrine which causes increased activity, increased heart rate and blood pressure. Their overdose most commonly causes heart attack, hyperthermia and brain damage.
In many cases, people who die of overdose are under influence of more than one drug whose synergistic effects are often lethal.

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