Isoforms, definition

RyR3 has been reported to be the major isoform in some smooth muscle tissues (Neylon et al 1995), but RyR2 has been reported to be the primary isoform expressed in urinary bladder smooth muscle (Chambers et al 1999), in which CICR has been definitively established (Ganitkevich Isenberg 1992, Imaizumi et al 1998, Collier et al 2000). RyRl has also been reported in smooth muscle at the expression and functional levels (Neylon et al 1995). It should be noted that determination of isoform expression has largely been reported using non-quantitative RT-PCR methods, with associated interpretive difficulties. 

When CYP2E1 was inhibited by intraperitoneal injection of DCE, levels of exhaled -hexane increased approximately 25-fold within 4 hours and returned to pre-dose levels at approximately 24 hours, closely paralleling the inhibition and resynthesis time-course for CYP2E1. No increase in lipid peroxidation was observed, indicating that the increase in exhaled -hexane was the result of inhibition of metabolism. It is probable that many P-450 isoforms are capable of hydroxylating -hexanc (both in vivo and under laboratory conditions) it is not possible at this time to specify which forms are definitely involved in -hexane metabolism in vivo. 

Apo(a) isoform size variability was subsequently found to result from differences in sizes of the hepatic apo(a) mRNA in both humans (K25) and baboons (H31) with few exceptions, apo(a) protein sizes were directly correlated to the size of the apo(a) transcript. Although studies suggested differences in the numbers of kringle IV repeats in the gene (G8, LI9), size variation in the apo(a) gene was definitively shown to result from differences in the number of tandemly... 

Alcohol consumption is very difficult to assess. There is widespread belief that individuals underreport their intake and there are no reliable laboratory tests available for definitive diagnosis of alcohol abuse. A combination of abnormalities in the plasma activity of gamma-glutamyl transferase (GGT or yGT), AST and reduction in erythrocyte mean cell volume (MCV) maybe useful and all are routine lab. tests. A potential marker of interest is carbohydrate-deficient transferrin (CDT) which is an abnormal isoform of serum transferrin arising due to defects in the attachment of carbohydrate chains to the protein core. Unfortunately, CDT is a somewhat specialized test, not performed by most laboratories. Other markers which have attracted some research interest are ethyl sulphate and ethyl glucuronide. Excretion in the urine of these metabolites occurs for up to 50 hours after binge drinking so they offer a useful index of recent heavy alcohol intake. 

There are cytosolic and membrane-bound isoforms of NO synthase. Certain soluble and particulate isoforms are constitutive and other soluble isoforms are inducible. The constitutive enzyme is, by definition, present in the catalytically active form and needs only to be stimulated by an appropriate chemical species, following which there is immediate formation of NO plus L-citrulline. This form of NO synthase requires calcium, and for the most part calmodulin, for stimulation of enzymatic activity. It is likely that an increase in intracellular free calcium in the presence of calmodulin is the signal for stimulation of NO synthase, and therefore, the production of NO. This view is consistent with the general understanding that, in vascular tissue, all endothelium-dependent vaso-... 

Analysis of dopamine-jS-hydroxylase activity in plasma can not be used to make a definitive diagnosis, as approximately 4% of the population have very low plasma activities. Support for such a diagnosis can come from examining the noradrenaline dopamine ratio in plasma. This is markedly reduced in this condition. Deficiencies of the MAO isoforms have been confirmed from enzymatic analysis of fibroblasts (MAO-A) or platelets (MAO-B). 

TABLE 20.3 Isofornns of moroamine oxidase MAO-A and MAO-B an explanation The table shows the definition of the isoforms b/ their specific substrates, and then their selectivity (or non selectivity) towards a number of other substrates and inhibitors. Determination of therapeutic and adverse effects is a function of selectivity of the inhibitor and the tissue location of the enzyme. ... 

The most definitive assessment of the metal composition of metalloproteins comes from the application of element-specific detection methods. CE-ICP-MS provides information not only about the type and quantity of individual metals bound to the proteins but also about the isotopes of each element as well [11,12]. Elemental speciation has become increasingly important to the areas of toxicology and environmental chemistry. Such analytical capability also opens up important possibilities for trace element metabolism studies. Figure 1 depicts the separation of rabbit liver metallothionein containing zinc, copper, and cadmium (the predominant metal) using CE-ICP-MS with a high-sensitivity, direct injection nebulizer (DIN) interface. UV detection (200 nm) was used to monitor the efficiency of the CE separation of the protein isoforms (MT-1 and MT-2), whereas ICP-MS detection made it possible to detect and quantify specific zinc, copper (not shown), and cadmium isotopes associated with the individual isoform peaks. 

All NSAIDs, by definition, inhibit COX enzymes to some degree. This prevents the metabolism of arachidonic acid to the unstable endoperoxide intermediate PGG2 (Ziel Krupp 1975). Currently two isoforms of the COX enzyme, known as COXl and COX2, have been described (Vane Dotting... 

While several functions for NO have been identified, the signal transduction pathway(s) that are utilized by NO at critical stages of ovarian development have not yet been definitively elucidated. The ecNOS- and iNOS-deficient mice provide excellent tools for the dissection of the relative functions for each isoform in the ovary. Furthermore, the study of ovarian NOS provides an experimental system in which the roles of ecNOS and iNOS in development (follicular and oocyte maturation) and differentiation (formation of the corpus luteum) can be studied. 

The previous discussion is especially apropos to the consideration of whether or not another tumor—pleomorphic leiomyosarcoma (PLMS)—can be defined as different from MFH. As described, PLMS is said to be immunoreactive for desmin or MSA or alpha-isoform actin, all of which may be seen in myofibroblastic elements as well (as in MFH). For now, a working definition of PLMS might require that positivity for at least two smooth muscle markers be observed. However, this stipulation is still not absolutely exclusionary with... 

This short and selective review indicates that research into laminin structure and function has become increasingly sophisticated. The immediate future promises discovery of an increasing family of laminin isoforms, allowing the characterization of their biological activities, a more definitive map of the active domains and the peptides which subtend them, the working out of anti-laminin modulating influences, and characterisation of the receptors interacting with these domains in vivo to mediate cellular responses. Such study should clarify the contexts by which laminin exerts its powerful influence on neuronal development. 

NO is freely diffusible in liver, how different isoforms affect hepatocytes differently remains to be determined. Although nitrotyrosine levels correlate with injury and reflect both oxidative and nitrosative stress, there is no definitive proof this is specifically involved in APAP-induced cell death. One interesting possibility that needs to be examined is whether mitochondrial NO is important in hepatotoxicity and if it is regulated by INK. 

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