Asparaginase

Asparaginase  is an enzyme that catalyzes the hydrolysis of asparagine to aspartic acid. It is marketed under the brand name Elspar, to treat acute lymphoblastic leukemia (ALL) and is also used in some mast cell tumor protocols.  Unlike other chemotherapy agents, it can be given as an intramuscular, subcutaneous, or intravenous injection without fear of tissue irritation.

Mechanism of action

The rationale behind asparaginase is that it takes advantage of the fact that ALL leukemic cells are unable to synthesize the non-essential amino acid asparagine, whereas normal cells are able to make their own asparagine; thus leukemic cells require high amount of asparagine. These leukemic cells depend on circulating asparagine. Asparaginase, however, catalyzes the conversion of L-asparagine to aspartic acid and ammonia. This deprives the leukemic cell of circulating asparagine.

Vaccines Animation

Vaccines is a biological preparation that improves immunity to a particular disease. A vaccine typically contains a small amount of an agent that resembles a microorganism. The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.

Vaccines can be prophylactic (e.g. to prevent or ameliorate the effects of a future infection by any natural or "wild" pathogen), or therapeutic (e.g. vaccines against cancer are also being investigated; see cancer vaccine).

Types

Vaccines are dead or inactivated organisms or purified products derived from them.

There are several types of vaccines currently in use.These represent different strategies used to try to reduce risk of illness, while retaining the ability to induce a beneficial immune response.

Killed

Vaccines containing killed microorganisms - these are previously virulent micro-organisms which have been killed with chemicals or heat. Examples are vaccines against flu, cholera, bubonic plague, polio and hepatitis A.

Attenuated

Some vaccines contain live, attenuated virus microorganisms. These are live micro-organisms that have been cultivated under conditions that disable their virulent properties, or which use closely-related but less dangerous organisms to produce a broad immune response. They typically provoke more durable immunological responses and are the preferred type for healthy adults. Examples include yellow fever, measles, rubella, and mumps. The live Mycobacterium tuberculosis vaccine developed by Calmette and Guérin is not made of a contagious strain, but contains a virulently modified strain called "BCG" used to elicit immunogenicity to the vaccine.

Toxoid

Toxoids - these are inactivated toxic compounds in cases where these (rather than the micro-organism itself) cause illness. Examples of toxoid-based vaccines include tetanus and diphtheria. Not all toxoids are for micro-organisms; for example, Crotalus atrox toxoid is used to vaccinate dogs against rattlesnake bites.

Subunit

Protein subunit - rather than introducing an inactivated or attenuated micro-organism to an immune system (which would constitute a "whole-agent" vaccine), a fragment of it can create an immune response. Characteristic examples include the subunit vaccine against Hepatitis B virus that is composed of only the surface proteins of the virus (produced in yeast) and the virus-like particle (VLP) vaccine against human papillomavirus (HPV) that is composed of the viral major capsid protein.

Conjugate

Conjugate - certain bacteria have polysaccharide outer coats that are poorly immunogenic. By linking these outer coats to proteins (e.g. toxins), the immune system can be led to recognize the polysaccharide as if it were a protein antigen. This approach is used in the Haemophilus influenzae type B vaccine.

Experimental

A number of innovative vaccines are also in development and in use:

* Recombinant Vector - by combining the physiology of one micro-organism and the DNA of the other, immunity can be created against diseases that have complex infection processes

* DNA vaccination - in recent years a new type of vaccine called DNA vaccination, created from an infectious agent's DNA, has been developed. It works by insertion (and expression, triggering immune system recognition) of viral or bacterial DNA into human or animal cells. Some cells of the immune system that recognize the proteins expressed will mount an attack against these proteins and cells expressing them. Because these cells live for a very long time, if the pathogen that normally expresses these proteins is encountered at a later time, they will be attacked instantly by the immune system. One advantage of DNA vaccines is that they are very easy to produce and store. As of 2006, DNA vaccination is still experimental.

* T-cell receptor peptide vaccines are under development for several diseases using models of Valley Fever, stomatitis, and atopic dermatitis. These peptides have been shown to modulate cytokine production and improve cell mediated immunity.

* Targeting of identified bacterial proteins that are involved in complement inhibition would neutralize the key bacterial virulence mechanism.

While most vaccines are created using inactivated or attenuated compounds from micro-organisms, synthetic vaccines are composed mainly or wholly of synthetic peptides, carbohydrates or antigens.

Valence

Vaccines may be monovalent (also called univalent) or multivalent (also called polyvalent). A monovalent vaccine is designed to immunize against a single antigen or single microorganism. A multivalent or polyvalent vaccine is designed to immunize against two or more strains of the same microorganism, or against two or more microorganisms. In certain cases a monovalent vaccine may be preferable for rapidly developing a strong immune response.

Vaccine. (2009, November 8). In Wikipedia, The Free Encyclopedia. Retrieved 07:59, November 9, 2009, from http://en.wikipedia.org/w/index.php?title=Vaccine&oldid=324652602

Bacteriorhodopsin

Bacteriorhodopsin is a protein used by archaea, most notably halobacteria. It acts as a proton pump, i.e. it captures light energy and uses it to move protons across the membrane out of the cell. The resulting proton gradient is subsequently converted into chemical energy.

Bacteriorhodopsin is an integral membrane protein usually found in two-dimensional crystalline patches known as "purple membrane", which can occupy up to nearly 50% of the surface area of the archaeal cell. The repeating element of the hexagonal lattice is composed of three identical protein chains, each rotated by 120 degrees relative to the others. Each chain has seven transmembrane alpha helices and contains one molecule of retinal buried deep within, the typical structure for retinylidene proteins.

It is the retinal molecule that changes its conformation when absorbing a photon, resulting in a conformational change of the surrounding protein and the proton pumping action. It is covalently linked to Lys216 in the chromophore by Schiff base action. After photoisomerization of the retinal molecule, Asp85 becomes a proton acceptor of the donor proton from the retinal molecule. This releases a proton from a "holding site" into the extracellular side (EC) of the membrane. Reprotonation of the retinal molecule by Asp96 restores its original isomerized form. This results in a second proton being released to the EC side. Asp85 releases its proton into the "holding site" where a new cycle may begin.

The bacteriorhodopsin molecule is purple and is most efficient at absorbing green light (wavelength 500-650 nm, with the absorption maximum at 568 nm).

The three-dimensional tertiary structure of bacteriorhodopsin resembles that of vertebrate rhodopsins, the pigments that sense light in the retina. Rhodopsins also contain retinal; however, the functions of rhodopsin and bacteriorhodopsin are different and there is only slight homology in their amino acid sequences. Both rhodopsin and bacteriorhodopsin belong to the 7TM receptor family of proteins, but rhodopsin is a G protein coupled receptor and bacteriorhodopsin is not. In the first use of electron crystallography to obtain an atomic-level protein structure, the structure of bacteriorhodopsin was resolved in 1990. It was then used as a template to build models of other G protein-coupled receptors before crystallographic structures were also available for these proteins.

Many molecules have homology to bacteriorhodopsin, including the light-driven chloride pump halorhodopsin (for whom the crystal structure is also known), and some directly light-activated channels like channelrhodopsin.

All other photosynthetic systems in bacteria, algae and plants use chlorophylls or bacteriochlorophylls rather than bacteriorhodopsin. These also produce a proton gradient, but in a quite different and more indirect way involving an electron transfer chain consisting of several other proteins. Furthermore, chlorophylls are aided in capturing light energy by other pigments known as "antennas"; these are not present in bacteriorhodopsin based systems. Lastly, chlorophyll-based photosynthesis is coupled to carbon fixation (the incorporation of carbon dioxide into larger organic molecules); this is not true for bacteriorhodopsin-based system. It is thus likely that photosynthesis independently evolved at least twice, once in bacteria and once in archaea.

"Bacteriorhodopsin." Wikipedia, The Free Encyclopedia. 23 Aug 2009, 19:24 UTC. 21 Oct 2009 <http://en.wikipedia.org/w/index.php?title=Bacteriorhodopsin&oldid=309646691>. 

The Ghrelin--Growth Hormone Lecture

Preimplantation Genetic Diagnosis

Preimplantation genetic diagnosis (PGD or PIGD) (also known as embryo screening) refers to procedures that are performed on embryos prior to implantation, sometimes even on oocytes prior to fertilization. PGD is considered another way to prenatal diagnosis. Its main advantage is that it avoids selective pregnancy termination as the method makes it highly likely that the baby will be free of the disease under consideration. PGD thus is an adjunct to assisted reproductive technology, and requires in vitro fertilization (IVF) to obtain oocytes or embryos for evaluation.

Indications and applications
Currently, there are mainly two groups of patients for which PGD is being applied:

In the first group PGD is used to look for a specific disorder in couples with a high risk of transmitting an inherited condition. This can be a monogenic disorder, meaning the condition is due to a single gene only, (autosomal recessive, autosomal dominant or X-linked disorders) or a chromosomal structural aberration (such as a balanced translocation). PGD helps these couples identify embryos carrying a genetic disease or a chromosome abnormality, thus avoiding the difficult choice of abortion. In addition, there are infertile couples who carry an inherited condition and who opt for PGD as it can be easily combined with their IVF treatment.

The second group consists of couples who undergo IVF treatment and whose embryos are screened for chromosome aneuploidies. The technique is not used to obtaining a specific prenatal diagnosis but rather for screening, properly referred to as preimplantation genetic screening (PGS), to increase the chances of an ongoing pregnancy. The main applications for PGS are an advanced maternal age, a history of recurrent miscarriages or repeated unsuccessful implantation. As the results of PGS rely on the assessment of a single cell, PGS has inherent limitations as the tested cell may not be representative of the embryo and embryo mosaicism may not be be clinically significant. Further, studies have not shown that IVF success rates in terms of live births are better when PGS is used, and there is some concern that a biopsy may lower success rates. It has also been proposed for patients with obstructive and non-obstructive azoospermia.

Signal Transduction in Disease and Response to DNA Damage Lecture

Nucleotide excision repair NER of carcinogen adducts

Nucleotide excision repair is a DNA repair mechanism. DNA constantly requires repair due to damage that can occur to bases from a vast variety of sources including chemicals, radiation and other mutagens. Nucleotide excision repair (NER) is a particularly important mechanism by which the cell can prevent unwanted mutations by removing the vast majority of UV-induced DNA damage (mostly in the form of thymine dimers and 6-4-photoproducts). The importance of this repair mechanism is evidenced by the severe human diseases that result from in-born genetic mutations of NER proteins including Xeroderma pigmentosum and Cockayne's syndrome. While the base excision repair machinery can recognize specific lesions in the DNA it can correct only damaged bases that can be removed by a specific glycosylase, the nucleotide excision repair enzymes recognize bulky distortions in the shape of the DNA double helix. Recognition of these distortions leads to the removal of a short single-stranded DNA segment that includes the lesion, creating a single-strand gap in the DNA, which is subsequently filled in by DNA polymerase, which uses the undamaged strand as a template. NER can be divided into two subpathways (Global genomic NER and Transcription coupled NER) that differ only in their recognition of helix-distorting DNA damage.