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Biomedical subjects

R Hume

Publications and source records attributed to R Hume.

At least 109 records · Page 6Linked to original sources
PubMed1989

A direct method for the diagnosis of human hepatic type 1b and type 1c glycogen-storage disease.

1. Type 1b and type 1c glycogen-storage disease are caused respectively by deficiencies of the glucose-6-phosphate translocase and the phosphate/pyrophosphate translocase of the human hepatic microsomal glucose-6-phosphatase system. 2. Current methods of unequivocally diagnosing type 1b and type 1c glycogen storage disease are indirect and complex. 3. We have therefore developed a simple, rapid and direct microfiltration assay for the glucose-6-phosphate translocase and the phosphate/pyrophosphate translocase. 4. We have demonstrated that the microfiltration assay can be used to directly diagnose type 1b and 1c glycogen-storage disease in microsomes isolated from hepatic needle-biopsy samples.

Antiporters↗
PubMed1989

Development of human liver UDP-glucuronosyltransferases.

The development of multiple UDPGT activities towards eight substrates has been studied in fetal term and adult post-mortem (less than 5 h after death) liver samples. Most fetal and term liver activities were less than 14% of adult values, except that towards 5-hydroxytryptamine which was present in fetal and term liver at adult levels. The majority of UDPGT activities develop to adult levels within 10-20 weeks postnatally, and even premature (30 weeks) which survive for up to 10 weeks will develop these enzyme activities. Immunoblot analysis of human liver microsomes and cDNA cloning of human UDPGT shows the existence of the family of isoenzymes in man, and it is important to determine the developmental pattern of individual drug glucuronidating enzymes in liver. Immunoblot analysis of developing liver shows the presence of two major UDPGT polypeptides in fetal liver, whereas more than five are observed in adult liver. The investigation of substrate specificity of individual UDPGTs by expression of cloned genes in COS-7 cells and the use of antibodies will facilitate the identification of enzymes present in perinatal liver.

Cloning, Molecular↗
PubMed1989

Studies on copper-zinc superoxide dismutase expression in developing human liver and kidney.

CuZn superoxide dismutase levels were found to be high in developing human kidney and liver compared to some other tissues including lung. In kidney, the enzyme was expressed in proximal and distal tubules, loop of Henle and collecting tubules and after 35 weeks of gestation it appeared to be distributed basally in proximal cells and luminally in distal cells. Glomerular structures were generally negative. CuZn superoxide dismutase was widely expressed in developing liver, with hepatocytes and bile duct epithelium demonstrating positivity. The low level of expression of CuZn superoxide dismutase in the glomerulus compared with the tubules was not expected since intrinsic glomerular cells demonstrate greater production of reactive oxygen species in response to some stimuli than do tubular cells. Expression of this enzyme may be determined by the need to generate hydrogen peroxide.

Cytosol↗
PubMed1989

Measurements of glutathione S-transferase B1 in plasma after birth asphyxia: an early indication of hepatocellular damage.

Concentrations of glutathione S-transferase (glutathione transferase; EC 2.5.1.18) B1 and B2 subunits (B1 and B2) and activity of alanine aminotransferase (ALT; EC 2.6.1.2) were measured in sequential plasma samples taken from 14 infants with birth asphyxia. Within 6 h of asphyxia, abnormal concentrations of B1 were found in 11 infants, whereas only seven infants showed abnormal ALT activities at this time. In plasma sampled 24 h after birth, values for ALT were abnormal in 10, whereas values for B1 were abnormal in six. Abnormal concentrations of B2 were found in relatively few of these infants, apparently because this monomer is poorly expressed in liver samples obtained up to 41 weeks after conception. We conclude that measurement of B1 may provide a useful index of hepatic impairment in birth-asphyxiated infants.

Asphyxia Neonatorum↗
PubMed1988

Identification of the human hepatic microsomal glucose-6-phosphatase enzyme.

The glucose-6-phosphatase enzyme protein of the human hepatic microsomal glucose-6-phosphatase system was identified as a 36.5 kDa polypeptide. The 36.5 kDa glucose-6-phosphatase enzyme protein was shown to be absent in the microsomes isolated from a patient previously diagnosed as having a type 1a glycogen storage disease.

Animals↗
PubMed1988

The human glutathione S-transferases. Immunohistochemical studies of the developmental expression of Alpha- and Pi-class isoenzymes in liver.

Immunohistochemical studies of the developmental expression of the Alpha- and Pi-class glutathione S-transferases in human liver have shown that the Pi enzyme is expressed in bile-duct epithelium and some hepatocytes but not in haematopoietic cells. This locus is down-regulated during gestation in hepatocytes but not in epithelium. The enzymes of the Alpha set were also found in only some hepatocytes, and it appears that many cells express neither these nor the Pi forms.

Adult↗
PubMed1988

A new microtechnique for the analysis of the human hepatic microsomal glucose-6-phosphatase system.

A microtechnique has been developed which enables a complete kinetic analysis of the human hepatic microsomal glucose-6-phosphatase system to be carried out in microsomes isolated from very small liver samples. Complete or partial deficiencies of any of the proteins of the glucose-6-phosphatase system resulting in Type 1a, 1b, 1c or 1d glycogen storage disease can be therefore be diagnosed using hepatic needle biopsy samples, whereas previous methods of diagnosis needed large wedge biopsy samples requiring laparotomy.

Female↗
PubMed1988

Studies on the expression of Cu,Zn superoxide dismutase in human tissues during development.

The developmental expression of Cu,Zn superoxide dismutase in human lung and erythrocytes has been studied using activity measurements, immunoblotting and immunohistochemistry. Enzyme activity in erythrocytes increased significantly during gestation but no developmental trend was seen in lung. Immunoblotting identified a single enzyme form that was present in a variety of tissues and immunohistochemistry showed the enzyme to have widespread distribution in lung tissue. These data indicate that Cu,Zn superoxide dismutase is consistently expressed during human development and that, unlike in other species, no late-fetal surge in expression occurs.

Cytosol↗
PubMed1988

The inadequacy of perinatal glucuronidation: immunoblot analysis of the developmental expression of individual UDP-glucuronosyltransferase isoenzymes in rat and human liver microsomes.

Two anti-rat UDP-glucuronosyltransferase (UDPGT) antibody preparations, exhibiting different specificity of recognition of UDPGT isoenzymes on immunoblot analysis, were used to investigate the molecular basis of the perinatal inadequacy of glucuronidation in rats and humans. Immunoblot analysis of microsomes from developing rat liver demonstrated that the deficiency in bilirubin and testosterone glucuronidation in the fetus was due to the absence of the UDPGT isoenzyme proteins responsible for these conjugations. In contrast, phenol UDPGT enzyme activity and protein was detectable in significant amounts in fetal rat liver (greater than 30% of adult levels). In human liver, only one major immunoreactive polypeptide was observed in fetal microsomes. The remaining UDPGTs present in adult human liver developed postnatally, in parallel with the appearance of enzyme activities. Therefore, there was a correlation between the development of enzyme activity and enzyme protein. The possible consequences of developmental inadequacy of conjugation reactions for the fetus is discussed.

Adult↗
PubMed1987

Studies on the developmental expression of glutathione S-transferase isoenzymes in human heart and diaphragm.

The developmental expression of the basic, near-neutral and acidic isoenzymes of glutathione S-transferase (RX:glutathione R-transferase, EC 2.5.1.18) has been studied in heart and diaphragm. Neither these enzymes nor the putative muscle-specific GST4 isoenzyme demonstrated any developmental trends in expression. In vitro hybridisation and SDS-discontinuous polyacrylamide gel electrophoresis were used to show that the GST4 isoenzyme is a homodimer composed of monomers that have a slightly larger molecular weight than the near-neutral isoenzyme. The sensitivity of GST4 to inhibitors also appeared similar to that of the GST1 2 isoenzyme. Immunodiffusion and immunoblotting techniques were used to show that the acidic enzyme in muscle is immunologically identical to that in other tissues.

Chromatography↗
PubMed1987

Development of multiple activities of UDP-glucuronyltransferase in human liver.

UDP-glucuronyltransferase activities towards eight substrates were assayed in samples of foetal, term and adult human liver. Activities towards bilirubin, androsterone, testosterone, 1-naphthol, 4-nitrophenol and 2-aminophenol were present in foetal and term liver samples at less than 14% of adult values, whereas activity towards 5-hydroxytryptamine was present in foetal and term liver at 109 and 121% of adult values respectively. Thus a 'foetal' form of UDP-glucuronyltransferase may exist in human liver that is more restricted in substrate specificity than are those of the rat or rhesus monkey.

Glucuronosyltransferase↗
PubMed1987

Studies of the development of basic, neutral and acidic isoenzymes of glutathione S-transferase in human liver, adrenal, kidney and spleen.

The ontogeny of basic, near-neutral and acidic glutathione S-transferase isoenzymes was studied by using chromatofocusing and ion-exchange chromatography. These isoenzyme sets demonstrated tissue-specific patterns of expression. For example, whereas basic isoenzymes were identified in all liver and adrenal cytosols obtained after 10 weeks gestation, these forms were not detected in kidney until 10 weeks post-natal age and in spleen until about 40 weeks post-natal age. Our data indicate that the basic monomers B1 and B2 are present in liver cytosol at 21 weeks gestation. Expression of the near-neutral isoenzymes was usually weak; for example, they were not generally expressed in liver until 30 weeks gestation, and no developmental patterns in their expression could be identified in adrenal, kidney and spleen. The acidic isoenzymes were usually strongly expressed in adrenal, kidney and spleen, although there was a decline in the level of expression in kidney after birth.

Adrenal Glands↗
PubMed1987

Sequential calcium and phosphorus balance studies in preterm infants.

Forty-six infant boys less than 1500 g at birth and less than 32 weeks gestation were fed enterally from birth until day 47. Cohorts were given milk formula varying in calcium and phosphorus content: group A, calcium 45 mg/dL, phosphorus 33 mg/dL; group B, calcium 85 mg/dL, phosphorus 33 mg/dL; group C, calcium 125 mg/dL, phosphorus 33 mg/dL; group D, calcium 125 mg/dL, phosphorus 50 mg/dL; and group E, calcium 125 mg/dL, phosphorus 64 mg/dL. Three-day balance studies were begun at days 10, 20, 30, and 40. Calcium net absorption and retention were influenced by postnatal age and calcium intake. Calcium retention best approached intrauterine accretion rates in group C. Phosphorus was well absorbed irrespective of the calcium content of the milk. Phosphorus retention increased with increments in the calcium content of the milk. Increasing the phosphorus content of the milk (groups D and E) resulted in no overall change in calcium absorption and retention but some increments in phosphorus retention.

Birth Weight↗
PubMed1987

Alkaline phosphatase isoenzymes in the plasma of preterm and term infants: serial measurements and clinical correlations.

Serial measurements of the bone and fetal intestinal isoenzymes of alkaline phosphatase (EC 3.1.3.1) in the plasma of 43 term and 43 preterm infants, from birth to six weeks later, indicate that the bone isoenzyme gradually increases over this period in both preterm and term infants fed with unsupplemented commercial formulas. Preterm babies given formula supplemented with calcium (with or without additional phosphate) had significantly lower bone isoenzyme activities for most of the study period. The concentrations of fetal intestinal isoenzyme increased, under the stimulation of milk feeding, from generally undetectable at birth to a peak during the first two weeks postpartum, and then declined. This increase was highly significantly negatively correlated with gestational age, the preterm infants having a much higher and more prolonged increase in this isoenzyme than did term infants. Unlike the adult isoenzyme, fetal intestinal alkaline phosphatase in plasma showed no relationship with blood group status.

Alkaline Phosphatase↗
PubMed1986

The development of glutathione S-transferase and glutathione peroxidase activities in human lung.

The development of glutathione S-transferase and glutathione peroxidase activities has been studied in human lung cytosols. Whilst no clear change in glutathione peroxidase activity was identified, expression of the acidic glutathione S-transferase isoenzyme decreased markedly after 15 weeks of gestation so that at birth the level of activity of this isoenzyme was only about 20% of that in samples obtained during the first trimester. Basic glutathione S-transferase isoenzymes were weakly expressed during development and usually comprised less than 10% of cytosolic activity. Ion-exchange studies identified several basic isoenzymes that may correspond to the alpha, beta, gamma, delta and epsilon set previously identified in liver. Weak expression of apparently near-neutral isoenzymes was also detected; they were detected in only a few cytosols.

Chromatography, Ion Exchange↗