GCSF Protein Folding Illustration Movie
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text info: Granulocyte Colony-Stimulating Factor (G-CSF or GCSF) is a colony-stimulating factor hormone. It is a glycoprotein, growth factor or cytokine produced by a number of different tissues to stimulate the bone marrow to produce granulocytes and stem cells. G-CSF then stimulates the bone marrow to pulse them out of the marrow into the blood. It also stimulates the survival, proliferation, differentiation, and function of neutrophil precursors and mature neutrophils.
G-CSF is also known as Colony-Stimulating Factor 3 (CSF 3). Granulocyte Colony-Stimulating Factor (G-CSF or GCSF) is a colony-stimulating factor hormone. It is a glycoprotein, growth factor or cytokine produced by a number of different tissues to stimulate the bone marrow to produce granulocytes and stem cells. G-CSF then stimulates the bone marrow to pulse them out of the marrow into the blood. It also stimulates the survival, proliferation, differentiation, and function of neutrophil precursors and mature neutrophils.
G-CSF is also known as Colony-Stimulating Factor 3 (CSF 3). Mouse granulocyte colony-stimulating factor (G-CSF) was first recognised and purified in Australia in 1983, and the human form was cloned by groups from Japan and the United States in 1986.
The G-CSF-receptor is present on precursor cells in the bone marrow, and, in response to stimulation by G-CSF, initiates proliferation and differentiation into mature granulocytes.
Genetics
The gene for G-CSF is located on chromosome 17, locus q11.2-q12. Nagata et al. found that the GCSF gene has 4 introns, and that 2 different polypeptides are synthesized from the same gene by differential splicing of mRNA.
The 2 polypeptides differ by the presence or absence of 3 amino acids. Expression studies indicate that both have authentic GCSF activity.
It is thought that stability of the G-CSF mRNA is regulated by an RNA element called the G-CSF factor stem-loop destabilising element.
Therapeutic use
G-CSF stimulates the production of white blood cells (WBC). In oncology and hematology, a recombinant form of G-CSF is used with certain cancer patients to accelerate recovery from neutropenia after chemotherapy, allowing higher-intensity treatment regimens. Chemotherapy can cause myelosuppression and unacceptably low levels of white blood cells, making patients prone to infections and sepsis. However, in a Washington University School of Medicine study using mice, G-CSF is shown to lessen the density of bone tissue even while it increases the WBC count; if this is found to occur in human cases it would necessitate increased consumption of calcium and vitamins A and D, and maybe drug therapy.
G-CSF is also used to increase the number of hematopoietic stem cells in the blood of the donor before collection by leukapheresis for use in hematopoietic stem cell transplantation. It may also be given to the receiver, to compensate for conditioning regimens.
Itescu planned in 2004 to use G-CSF to treat heart degeneration by injecting it into the blood-stream, plus SDF (stromal cell-derived factor) directly to the heart.
The recombinant human G-CSF synthesised in an E. coli expression system is called filgrastim. The structure of filgrastim differs slightly from the structure of the natural glycoprotein. Most published studies have used filgrastim. Filgrastim (Neupogen®) and PEG-filgrastim (Neulasta®) are two commercially-available forms of rhG-CSF (recombinant human G-CSF). The PEG (polyethylene glycol) form has a much longer half-life, reducing the necessity of daily injections.
Another form of recombinant human G-CSF called lenograstim is synthesised in Chinese Hamster Ovary cells (CHO cells). As this is a mammalian cell expression system, lenograstim is indistinguishable from the 174-amino acid natural human G-CSF. No clinical or therapeutic consequences of the differences between filgrastim and lenograstim have yet been identified, but there are no formal comparative studies.
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protein folding modelling 3D pymol
Added: July 7, 2009, 1:11 am
Runtime: 66.00 | Views: 6181 |
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Proton pump inhibitors
Proton pump inhibitors (or "PPI"s) are a group of drugs whose main action is pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar effects, but different mode-of-action, called H2-receptor antagonists. These drugs are among the most widely-selling drugs in the world as a result of their outstanding efficacy and safety. Structurally, the vast majority of these drugs are benzimidazole derivatives; however, promising new research indicates that imidazopyridine derivatives may be a more effective means of treatment.
Mechanism of action
Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ATPase, or more commonly just gastric proton pump) of the gastric parietal cell. The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion. Targeting the terminal-step in acid production, as well as the irreversible nature of the inhibition, result in a class of drugs that are significantly more effective than H2 antagonists and reduce gastric acid secretion by up to 99%.
The lack of the acid in the stomach will aid in the healing of duodenal ulcers, and reduces the pain from indigestion and heartburn, which can be exacerbated by stomach acid. However, lack of stomach acid may also contribute to hypochlorhydria, a lack of sufficient hydrochloric acid, or HCl. Hydrochloric acid is required for absorption of nutrients, particularly calcium.
The proton pump inhibitors are given in an inactive form. The inactive form is neutrally charged (lipophilic) and readily crosses cell membranes into intracellular compartments (like the parietal cell canaliculus) that have acidic environments. In an acid environment, the inactive drug is protonated and rearranges into its active form. As described above, the active form will covalently and irreversibly bind to the gastric proton pump, deactivating it. Adverse effects
Proton pump inhibitors are generally well tolerated, and the incidence of short-term adverse effects is relatively uncommon. The range and occurrence of adverse effects are similar for all of the proton pump inhibitors, though they have been reported more frequently with omeprazole. This may be due to its longer availability and hence clinical experience.
Common adverse effects include: headache, nausea, diarrhea, abdominal pain, fatigue, dizziness.
Infrequent adverse effects include: rash, itch, flatulence, constipation. Decreased cyanocobalamin (vitamin B12) absorption may occur with long-term use. Rarely PPI cause ‘idiosyncratic’ reactions such as erythema multiforme, pancreatitis, Stevens Johnson syndrome and acute interstitial nephritis.
It has been observed that gastric acid suppression, using H2-receptor antagonists and proton pump inhibitors, is associated with an increased risk of community-acquired pneumonia. It is suspected that acid suppression results in insufficient elimination of pathogenic organisms. It has therefore been suggested that patients at higher risk of pneumonia should only be prescribed proton pump inhibitors at lower doses and only when necessary.
PPIs have also been shown to raise risk of C. dif infection.
Long-term use of proton pump inhibitors has been less studied. But in a study of 135,000 people 50 or older, those taking high doses of PPIs for longer than one year have been found to be 2.6 times more likely to break a hip. Those taking smaller doses for 1 to 4 years were 1.2 to 1.6 times more likely to break a hip. The risk of a fracture increased with the length of time taking PPIs. Theories as to the cause of the increase are the possibility that the reduction of stomach acid reduces the amount of calcium dissolved in the stomach or that PPIs may interfere with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts
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Proton pump inhibitors
Added: July 7, 2009, 1:13 am
Runtime: 65.00 | Views: 9412 |
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How the Body Works : The Olfactory Pathway
The Olfactory Pathway
Air inhaled through the nose passes over the olfactory membranes, where chemicals that are in the air stimulate the numerous olfactory receptor cells. The smell information passes from the receptor-cell neurons to the bulbs and tracts of the first cranial nerve, which pass into the frontal lobes of the brain. Each tract divides into medial and lateral striae, which pass the information to the olfactory cortex, where smell is perceived.
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The Olfactory Pathway
Added: July 7, 2009, 1:15 am
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Cycle sequencing
To sequence a piece of dna you need 1)a Template DNA 2) a short DNA primer that is complementary to the dna you want to sequence, 3)A enzyme called DNA polymerase,(4) Four nucleotides.(A,C,G,T), To this mix ,we also add a second type of nucleotide; one that has a slightly different chemical formula, These dideoxynucleotides(diddtp) can be recognized by a DNA sequencer.
To start the sequencing reaction this mixture is heated to 96C ,so the template DNA's two complementary strand separates,Then the temperature is lowered, so that the short "primer" sequence finds its complementary sequence in the template DNA.Finally the temperature is raised 60c,this allows the enzyme to bind to the DNA and create a new strand of DNA. The sequence of this new DNA is complementary to the original DNA strand. The enzyme makes no distinction between dNTPs or didNTPs.each time a didNTP is incorporated, in this case didATP,The synthesis stops. Because billion of DNA molecules are present in the test tube, the strand can be terminated at any position. This results in collection of DNA strands of many different lengths.
The sequencing reaction is transferred from the test tube to a lane of a polyacrylamide gel. The gel is placed into a DNA sequencer for electrophoresis and analysis. The fragments migrate according to size and each is detected as it passes a laser beam at the bottom of the gel. Each type of dideoxynucleotide emits colored light of a characteristic wavelength and is recorded as a colored band on a simulated gel image, and finally computer program interprets the raw data and outputs an electropherogram with colored peaks representing each letter in the sequence.the sequence fragments are sorted out according to the size, starting from the shortest to longest one, the stimulated gel image is read from bottom to top, starting with the smallest fragment, Thus we sequences present in template DNA.
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Cycle sequencing
Added: July 7, 2009, 1:21 am
Runtime: 255.00 | Views: 3897 |
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