Tissue typing

S. E. Builder, R. van Reis, N. Paoni, and J. Ogez, "Process Development and Regulatory Approval of Tissue-Type Plasminogen Activator," in... 

The symptoms of vitamin E deficiency in animals are numerous and vary from species to species (13). Although the deficiency of the vitamin can affect different tissue types such as reproductive, gastrointestinal, vascular, neural, hepatic, and optic in a variety of species such as pigs, rats, mice, dogs, cats, chickens, turkeys, monkeys, and sheep, it is generally found that necrotizing myopathy is relatively common to most species. In humans, vitamin E deficiency can result from poor fat absorption in adults and children. Infants, especially those with low birth weights, typically have a vitamin E deficiency which can easily be corrected by supplements. This deficiency can lead to symptoms such as hemolytic anemia, reduction in red blood cell lifetimes, retinopathy, and neuromuscular disorders. 

Previously, pharmacologists were constrained to the prewired sensitivity of isolated tissues for agonist study. As discussed in Chapter 2, different tissues possess different densities of receptor, different receptor co-proteins in the membranes, and different efficiencies of stimulus-response mechanisms. Judicious choice of tissue type could yield uniquely useful pharmacologic systems (i.e., sensitive screening tissues). However, before the availability of recombinant systems these choices were limited. With the ability to express different densities of human target proteins such as receptors has come a transformation in drug discovery. Recombinant cellular systems can now... 

Fibrinolytics. Figure 3 Plasminogen activation (a) Kinetics of plasminogen activation by uPA (urokinase-type) and tPA (tissue-type) plasminogen activators. Effect of fibrin (b) Ternary complex formation between enzyme (tPA), substrate (Pg) and cofactor (F) Abbreviations plasmin (P), fibrin (F), plasminogen (Pg). Plasmin, formed in time, is expressed in arbitrary units. 

Tissue-type plasminogen activator (tPA) is a glycoprotein (68 kDa), synthesized by endothelial and tumor-cells. As a serine protease, tPA hydrolyses Arg561-Val562 peptide bond in plasminogen, resulting in plasmin formation. It needs cofactors for efficient plasminogen activation. 

Tissue-specific Agonists/Antagonists Tissue-type Plasminogen Activator T-kinin (Ile-Ser-Bradykinin)... 

Recently, a superior therapy has been approved for use by the federal government tissue-type plasminogen activator (tPA). This naturally occurring enzyme dissolves blood clots as part of the normal healing process. By administering relatively large quantities of it, clot breakdown time can be shortened from about a week to under an hour. 

Figure 22.1 A. Schema for a physiologically based pharmacokinetic model incorporating absorption in the stomach and intestines and distribntion to various tissues. B. Each organ or tissue type includes representation of perfusion (Q) and drug concentrations entering and leaving the tissue. Fluxes are computed by the product of an appropriate rate law, and permeable surface area accounts for the affinity (e.g., lipophilic drugs absorbing more readily into adipose tissue). Clearance is computed for each tissue based on physiology and is often assumed to be zero for tissues other than the gut, the liver, and the kidneys.

DNA sequences as short as 50-100 bp and as long as 10 kb can be amplified. Twenty cycles provide an amplification of 10 and 30 cycles of 10. The PCR allows the DNA in a single cell, hair follicle, or spermatozoon to be amplified and analyzed. Thus, the applications of PCR to forensic medicine are obvious. The PCR is also used (1) to detect Infectious agents, especially latent viruses (2) to make prenatal genetic diagnoses (3) to detect allelic polymorphisms (4) to establish precise tissue types for transplants and (5) to study... 

As shown in Figure 48-8, the keratan sulfates consist of repeating Gal-GlcNAc disaccharide units containing sulfate attached to the 6 position of GlcNAc or occasionally of Gal. Type 1 is abundant in cornea, and type II is found along with chondroitin sulfate attached to hyaluronic acid in loose connective tissue. Types I and II have different attachments to protein (Figure 48—8). 

Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999 282 2019-2026 [see comment]. 

Papadopoulos SM, Chandler WF, Salamat MS, Topol EJ, Sackellares JC. Recombinant human tissue-type plasminogen activator therapy in acute thromboembolic stroke. J Neurosurg. 1987 67 394-398. 

Katzan IL, Furlan AJ, Lloyd LE, Erank JI, Harper DL, Hinchey JA, Hammel JP, Qu A, Sila CA. Use of tissue-type plasminogen activator for acute ischemic stroke The Cleveland area experience. JAMA. 2000 283 1151-1158. 

Albers GW, Bates VE, Clark WM, Bell R, Verro P, Hamilton SA. Intravenous tissue-type plasminogen activator for treatment of acute stroke The Standard Treatment with Alteplase to Reverse stroke (STARS) study. JAMA. 2000 283 1145-1150. 

Katzan IL, Hammer MD, Eurlan AJ, Hixson ED, Nadzam DM. Quality improvement and tissue-type plasminogen activator for acute ischemic stroke A Cleveland update. Stroke. 2003 34 799-800. 

Grotta JC, Burgin WS, El-MitwaUi A, Long M, Campbell M, Morgenstem LB, Malkoff M, Alexandrov AV. Intravenous tissue-type plasminogen activator therapy for ischemic stroke Houston experience 1996 to 2000. Arch Neurol. 2001 58 2009-2013. 

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