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Biomedical subjects

R C Strange

Publications and source records attributed to R C Strange.

At least 145 records · Page 8Linked to original sources
PubMed1985

The human glutathione S-transferases: developmental aspects of the GST1, GST2, and GST3 loci.

The expression of the GST1, GST2, and GST3 loci in fetal, neonatal, and infant tissues has been studied using starch gel electrophoresis and chromatofocusing. Each locus demonstrated developmental changes in expression, some of which were specific to a single tissue while others occurred in several tissues. GST1 was not usually expressed in any of the tissues studied before 30 weeks of gestation but steadily increased thereafter until adult levels were reached in late infancy. In neonates and older infants the frequencies of the GST1*0, GST1*1, and GST1*2 alleles were 0.79, 0.07, and 0.14, respectively. GST2 was always expressed in liver and adrenal but was only weakly expressed in spleen, cardiac muscle, and diaphragm. In kidney this locus was not usually expressed until nearly 1 year after birth. The GST3 isoenzymes were present in all fetal, neonatal, and infant tissues, although their expression in liver decreased after 30 weeks of gestation. Other isoenzymes with fast anodal mobilities were also identified in several tissues; these are believed to be GST3 isoenzymes that have undergone posttranslational modification rather than products of the putative GST4 locus. No specifically fetal isoenzymes were detected.

Chromatography↗
PubMed1985

Plasma bile salt levels in patients presenting with generalised pruritus: an improved indicator of occult liver disease.

Fasting plasma bile salt concentrations were measured in 26 patients presenting to a Skin Department who had generalised pruritus without primary skin disease, as part of a screening investigation for systemic causes of pruritus. The results were compared with conventional tests of hepatic function. Plasma-conjugated cholate measurements identified all patients with hepatobiliary disease. Conventional liver function tests were abnormal in these patients but also in five patients with no other evidence of hepatic dysfunction. Fasting conjugated-cholate measurements offer a useful screening test for identifying hepatobiliary disease in patients presenting with generalised pruritus.

Adult↗
PubMed1984

Studies on the glutathione S-transferase of human platelets.

The glutathione S-transferases of human platelets have been compared with those of erythrocytes. Although wide variations in activity were found, in individual subjects, the activity in these cell types was significantly correlated. The enzymes demonstrated similar isoelectric points and electrophoretic mobilities and it appears that the platelet enzyme is also a product of the GST3 locus. There was no correlation between platelet enzyme activity and plasma concentrations of retinol and cholesterol, but in men, the relationship between activity and carotene was significant. It is suggested that GST3 isoenzyme activity depends on vitamin A.

Adolescent↗
PubMed1984

The human glutathione S-transferases: studies on the tissue distribution and genetic variation of the GST1, GST2 and GST3 isozymes.

Three sets of isozymes of glutathione-S-transferase (GST) have been identified in human tissues. They differ in their tissue distribution, incidence of genetic variation, susceptibility to inactivation by N-ethylmaleimide and in their electrophoretic mobilities. The GST1 isozymes exhibit four phenotypes, including a common 'null' phenotype attributable to different combinations of three autosomal alleles GST1 1, GST1 2 and GST1 0 of frequency 0.13, 0.23 and 0.64, respectively, in the European population. The genetic polymorphism of GST1 is easily demonstrable in adult liver, kidney, adrenal and stomach but the isozymes are only weakly expressed in skeletal and cardiac muscle and not at all in fetal liver, fibroblasts, erythrocytes, lymphocytes and platelets. The GST2 isozymes also exhibit variant patterns but these are probably due to post-synthetic modification rather than allelic variation. The GST2 isozymes are not detectable in erythrocytes, platelets, cultured fibroblasts or lymphocytoid cells but are found in many other tissues, including fetal liver. GST3 isozymes were found as relatively strong components in every tissue examined except adult liver, with slight tissue to tissue variability in electrophoretic mobility.

Adrenal Glands↗
PubMed1984

Hepatic bile flow.

The hepatocyte is a polar cell that can remove a variety of molecules from blood and excrete them into bile. This review is primarily concerned with the mechanism of transport of the principal anions--the bile salts--across the sinusoidal membrane, their passage through the cell, and excretion across the canalicular membrane. Clearly much of this process is poorly understood, but the study of the membrane stages should be facilitated by the ability to prepare purified sinusoidal and canalicular membrane vesicles. For example, the relative importance of albumin-binding sites as well as the putative bile salt receptor proteins can be better assessed. It seems likely that although the interaction of bile salts with receptor proteins is important, it is an initial event that puts the bile salt in the correct place for uptake to occur. The driving force for uptake is the Na+ gradient created across the basolateral membrane by the activity of the Na+-K+-ATPase. Within the cell, various modes of transport have been suggested. Several authors emphasize the importance of protein binding of bile salts, either because of their presumed ability to maintain the concentration of these anions in the hepatocyte below their critical micellar concentration or because of their putative role in transport. It is important to understand these aspects of the role of cytosolic proteins for several reasons. Knowledge of the true concentration of free bile salt within the cell should allow estimation of whether the electrochemical gradient is sufficient for bile salts to accumulate in bile without the need for active transport of molecules from the cell into the canaliculus. The compartmental model described by Strange et al. (153) offers one theoretical way of determining the concentration of free bile salt, although the problems inherent in studying amphipath binding to the membranes of subcellular organelles (31) require that the model be reevaluated by the hygroscopic-desorption method. The second role suggested for the cytosolic bile salt-binding proteins is as transport proteins. As discussed in section VI, I think it is unlikely that the proteins identified so far act in this way, and it is more likely that movement occurs by diffusion in free solution. It is also important to determine the possible involvement of subcellular organelles such as Golgi bodies. Little is known of their role in the transport of bile salts or indeed where bile salt micelles are formed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Assessment of liver function using fasting bile salt concentrations in psoriasis prior to and during methotrexate therapy.

To determine if fasting bile salt concentrations are an accurate indicator of pre-existing and methotrexate-induced liver disease in patients with psoriasis, the plasma concentrations of conjugated cholate, chenodeoxycholate and sulpholithocholate were measured in 18 patients being assessed for methotrexate therapy and 21 receiving long-term therapy. The results were compared with other liver function tests and liver histology. The liver function tests were a poor indicator of occult liver disease and, whilst fasting bile salts appeared more sensitive, they were still unreliable and inadequate for the clinical assessment of the hepatopathy associated with psoriasis. The reasons for these discrepancies are discussed.

Adult↗
PubMed1982

Studies on the variability of glutathione S-transferase from human erythrocytes.

Glutathione S-transferase activity has been measured in erythrocytes from 101 subjects. Specific activity in the female subjects was significantly greater than that in the males, but there was no relationship in either sex between enzyme activity and age or between enzyme activity and the most common erythrocyte antigens. Separation of erythrocytes by age using isopycnic centrifugation showed that enzyme activity was constant during the life of the cell.

Adolescent↗
PubMed1982

Plasma alkaline phosphatase activity in rickets of prematurity.

Plasma alkaline phosphatase activity was measured in 349 infants aged between 5 and 10 days to establish a normal range for different gestational ages. Significant differences were observed between term and preterm infants, the highest values being associated with the shortest lengths of gestation. Plasma calcium, phosphate, and alkaline phosphatase activity were measured sequentially in 51 preterm infants less than 1500 g at birth. A significant correlation was found between raised plasma alkaline phosphatase activity and radiological changes of osteoporosis, metaphyseal change, and periosteal reaction. Plasma alkaline phosphatase appears to be of value in screening for and monitoring rickets of prematurity.

Alkaline Phosphatase↗
PubMed1981

A study of the structures of the YaYa and YaYc glutathione S-transferases from rat liver cytosol. Evidence that the Ya monomer is responsible for lithocholate-binding activity.

The two dimeric lithocholic acid-binding proteins previously identified as ligandin (YaYa) and glutathione S-transferase B (YaYc) were isolated from rat liver cytosol. These proteins have molecular weights of 44000 and 47000 respectively. The recovery of these two proteins from liver was not affected by the addition of the proteinase inhibitor Trasylol. No spontaneous interconversion between these two proteins was observed on storage. YaYa and YaYc proteins yielded peptides of identical molecular weight after limited digestion with Staphylococcus aureus V8 proteinase. Analytical and preparative tryptic-digest peptide 'maps' showed that all the soluble peptides obtained from YaYa protein were also recovered from YaYc protein. Approximately six extra soluble peptides, which were not recovered from YaYa protein, were obtained from the tryptic digest of YaYc protein. Subdigests of the insoluble tryptic-digest 'cores' also resulted in the recovery of identical peptides from both proteins. Evidence is presented that the Ya subunit possessed by both proteins is identical; glutathione S transferase B is a hybrid of ligandin and glutathione S-transferase AA. The Ya monomer is responsible for lithocholate binding.

Animals↗
PubMed1981

Hepatic bile salt transport. A review of subcellular binding sites.

Bile-salt transport is an example of the remarkable ability of the liver to remove anions rapidly and efficiently from blood and excrete them into bile. It appears that uptake of bile salts involves receptor proteins in the hepatocyte membrane whereas transport across the cell is by diffusion in free solution. Excretion into bile may also require receptor proteins. It is worth emphasizing that many of the studies described in this review were performed in rats. Unlike humans the rat does not possess a gall bladder and it seems likely, therefore, that in this animal hepatic bile-salt uptake will occur at a relatively constant rate throughout the day. In the human, however, little uptake will occur during periods of fasting, since the bile-salt pool is retained in the gall bladder.

Animals↗
PubMed1981

Distribution of glycocholate in blood from human fetuses and adults.

Glycocholate binding by plasma proteins and erythrocytes from fetal and adult blood has been studied, and the results have been used to derive a compartmental model of the distribution of glycocholate in blood. This model assumes that glycocholate is distributed between the aqueous phase, albumin binding sites, binding sites on other plasma proteins, and erythrocytes. Whereas glycocholate binding by albumin was saturable [fetal blood: dissociation constant (0.5 mM), concentration of binding sites (11.3 mumoles/g protein); adult blood: dissociation constant (0.42 mM), concentration of binding sites (20.1 mumoles/g protein)], binding by other plasma proteins was not. The association of glycocholate with erythrocytes appeared to be based on partitioning rather than binding of the bile salt to specific sites. The value of the partition coefficient was 6.0. The compartmental model indicates that, in fetal blood, 46% of the glycocholate is in free solution, and 37% is bound to albumin. In blood from adults, the corresponding values are 31% in free solution and 59% bound to albumin.

Adult↗
PubMed1980

A comparison of erythrocyte glutathione S-transferase activity from human foetuses and adults.

Glutathione S-transferase activity was measured in partially purified haemolysates of erythrocytes from human foetuses and adults. Enzyme activity was present in erythrocytes obtained between 12 and 40 weeks of gestation. The catalytic properties of the enzyme from foetal cells were similar to those of the enzyme from adult erythrocytes, indicating that probably only one form of the erythrocytes enzyme exists throughout foetal and adult life.

Chromatography, Gel↗
PubMed1980

The glyceryl [14C]tripalmitate breath test: a reassessment.

Several reports have been published commending the use of 14C-labelled triglyceride breath tests in the assessment of fat malabsorption. We report further studies using gyceryl [14C]tripalmitate. Corrections for age, weight or metabolic rate failed to improve the test's ability to discriminate between malabsorbers and control subjects. A correction for respiratory quotient improved the linear correlation observed between the breath test results and daily faecal fat excretion. The significance of these findings is discussed and a number of problems identified which, at present, are preventing the introduction of breath tests for fat malabsorption into routine clinical practice.

Adult↗
PubMed1980

Cholic acid binding by glutathione S-transferases from rat liver cytosol.

Cholic acid-binding activity in cytosol from rat livers appears to be mainly associated with enzymes having glutathione S-transferase activity; at least four of the enzymes in this group can bind the bile acid. Examination of the subunit compositions of different glutathione S-transferases indicated that cholic acid binding and the ability to conjugate reduced glutathione with 1,2-dichloro-4-nitrobenzene may be ascribed to different subunits.

Animals↗