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Biomedical subjects

R Hume

Publications and source records attributed to R Hume.

At least 91 records · Page 5Linked to original sources
PubMed1991

Developmental profile of plasma proteins in human fetal cerebrospinal fluid and blood.

Total protein, alphafetoprotein, albumin, prealbumin, alpha-1-antitrypsin, transferrin and ceruloplasmin levels were measured in samples of human fetal and neonatal cerebrospinal fluid (CSF) (97 cases), obtained between 12 and 41 weeks of gestation. In 39 of these cases (13 to 40 weeks gestation) plasma was also available for comparative analysis. CSF was collected from lateral ventricles in the first half of gestation and from the lumbar region in the second. Since these CSF samples were obtained from different sites, the protein levels in the lateral ventricle (early) samples could not be compared directly with those in the lumbar (later) samples. However, the mean protein levels in the lumbar samples were lower than those in the ventricular samples, which is in accord with the decline in CSF protein levels described in maturing animal fetuses. Despite a wide scatter of results, particularly in the first half of gestation, significant decline in the level of CSF alphafetoprotein was demonstrated during both first and second halves of gestation, and of albumin and prealbumin in the second half. No sex differences were found except for ceruloplasmin in lumbar CSF later in gestation, when males had higher levels than females. In fetal plasma, protein levels increased with increasing gestation apart from alphafetoprotein and prealbumin which both declined progressively. CSF/plasma ratios were dissimilar for different proteins, and changed with increasing gestation. These findings support the concept that the human fetal blood brain barrier matures early.

Blood Proteins↗
PubMed1991

Improved preparation of hepatic microsomes for in vitro diagnosis of inherited disorders of the glucose-6-phosphatase system.

Disruption of microsomal membranes after freezing liver samples can undermine the reliability of in vitro enzymatic diagnosis of the type 1 glycogen storage diseases. However, freezing of biopsy material is necessary if biopsy samples are to be safely transported to the place of assay. We have therefore examined several different methods (each of which could easily be carried out in routine hospital laboratories) of preparing and freezing liver tissue before analysis for glucose-6-phosphatase (EC 3.1.3.9) enzyme activity, and determination of microsomal intactness. Our study showed that homogenizing fresh liver, and centrifuging the homogenate at 10,000 x g for 10 min at 4 degrees C, followed by freezing the resulting supernatant material at -80 degrees C, provided the optimum source of material for subsequent preparation of microsomes for analysis of glucose-6-phosphatase activity. We also demonstrated that 1-naphthol UDP glucuronosyltransferase (EC 2.4.1.17) activity could be used to assess microsomal intactness in cases of type 1a glycogen storage disease, where mannose-6 phosphatase activity cannot be used.

Animals↗
PubMed1990

Human glutathione S-transferases: radioimmunoassay studies on the expression of alpha-, mu- and pi-class isoenzymes in developing lung and kidney.

The developmental expression of the alpha-, mu- and pi-class glutathione S-transferases has been defined in human lung and kidney using radioimmunoassay, immunohistochemistry and column chromatography. Expression of alpha-class enzymes increased significantly after about 40 weeks gestation in kidney but not lung, while expression of mu isoenzymes was continuous throughout development in both tissues. Expression of the pi isoenzyme fell during in utero ontogeny in lung, the pattern of down-regulation being similar to that previously observed in liver. There was no change in the expression of this isoenzyme in kidney. Comparison of the expression of the glutathione S-transferases in developing lung, kidney and liver shows some common patterns of expression suggesting these genes are under similar regulatory control.

Down-Regulation↗
PubMed1990

Membrane specific carbonic anhydrase (CAIV) expression in human tissues.

Membrane-bound carbonic anhydrase IV (CAIV) expression has been evaluated in a range of fetal and adult human tissues and in cell culture. All tissues tested showed expression of CAIV, assessed by Western blotting, with a single immunodetected band at 55 kDa. The levels varied in fetal lung and liver during development and in various zones of the fetal brain. CAIV was clearly expressed in lung, pancreatic tumour and skin cell cultures.

Blotting, Western↗
PubMed1990

The alpha and pi isoenzymes of glutathione S-transferase in human fetal lung: in utero ontogeny compared with differentiation in lung organ culture.

Polyclonal antisera to the alpha and pi isoenzymes of glutathione S-transferase have been used in immunohistochemical studies of developing human lung. In utero expression of the pi set was down-regulated in distal airway cells and the first appearance of pi-negative cells coincided with phenotypic differentiation. In contrast, in the early phase of fetal lung organ culture pi isoenzyme was detected in all differentiated epithelial cells and only as culture progressed did focal negativity develop. The alpha set showed no developmental changes in utero or in organ culture.

Down-Regulation↗
PubMed1990

Magnesium metabolism in preterm infants: effects of calcium, magnesium, and phosphorus, and of postnatal and gestational age.

This study tests the hypothesis that increasing the calcium and phosphorus content of formulas for very low birth weight (VLBW) infants to the level required to decrease the incidence of rickets has a negative impact on magnesium balance. Using formulas variously supplemented with these minerals, we measured absorption and retention in two groups of preterm infants: (1) VLBW infants, less than 1500 gm and at less than 32 weeks of gestational age, with 3-day mineral balances begun at days 10, 20, 30, and 40; and (2) low birth weight infants appropriately grown and at 32 to 34 weeks of gestational age, with a single 3-day balance begun at day 10. Magnesium did not affect calcium balance in VLBW or low birth weight infants but promoted phosphorus retention in VLBW infants from day 20 onward. Absorption and retention of magnesium increased with postnatal age in VLBW infants, but this effect was obvious only when calcium or phosphorus intakes were low or when magnesium intake was high. Calcium and phosphorus supplementation further reduced magnesium absorption and retention in VLBW infants to the extent that they were in negative balance throughout the study; however, magnesium supplementation improved absorption and retention in VLBW infants. The low birth weight infants absorbed and retained more magnesium than VLBW infants at the same postnatal age whether or not magnesium was supplemented. We conclude that magnesium deficits occur at currently recommended intakes of 10 mg/kg/day for VLBW infants with calcium and phosphorus intakes that allow retentions equivalent to in utero accretions; however, with magnesium intakes approaching 20 mg/kg/day, appropriate retention can be achieved.

Absorption↗
PubMed1990

Glial and neuronal differentiation in the human fetal brain 9-23 weeks of gestation.

Nineteen human fetal brains ranging from 9-23 weeks of gestation were examined immunocytochemically for evidence of glial and neuronal differentiation. Radial glia were positive for vimentin and glial fibrillary acidic protein (GFAP) throughout the age range. S100-positive cells which were presumed to be astrocytes were present from 9 weeks; they were always more widespread in the cerebrum and the brainstem than GFAP-positive mature astrocytes, which could be detected with certainty only at 14 weeks. Carbonic anhydrase II (CA II)-positive oligodendrocytes were present in the brainstem in small numbers from 17 weeks. Neuronal fibre tracts in the cerebrum were positive for 160 kD phosphorylated neurofilament protein (BF10) from 9 weeks, but negative for 200 kD phosphorylated neurofilament protein (RT97) and for 70 and 200 kD non-phosphorylated neurofilament protein (NFP) whereas most tracts in the brainstem were positive for BF10 from 9 weeks and positive for the other neurofilament proteins from 14 weeks. Corticospinal tracts differed in remaining negative for neurofilament proteins other than BF10, which showed positive reaction throughout. Perikarya of differentiated neurons in all areas of the brain were neurofilament-negative but neuron specific enolase (NSE)-positive. Germinal eminence cells were focally vimentin-positive from 15 weeks, focally GFAP-positive from 17 weeks, and negative for all NFP and for NSE. The value of a short fixation time and pretreatment with trypsin in the immunocytochemical demonstration of GFAP is stressed.

Brain↗
PubMed1990

Glutathione S-transferase in human brain.

The glutathione S-transferases are a complex group of multifunctional enzymes which may detoxify a wide range of toxic substances including drugs and carcinogens. Different isoenzymes vary in substrate specificity, tissue distribution and level of expression during development. Following reports of cell-specific and age-dependent expression in rat brain we have studied, immunohistochemically, expression of the Pi and Alpha class isoenzymes in 10 adult and 21 human fetal brains. Whilst Alpha isoenzyme is expressed only in adult brain, and then only focally, Pi isoenzyme is strongly expressed from as early as 12 weeks gestation. In the adult, expression is localized to choroid plexus, vascular endothelium, ventricular lining cells, pia-arachnoid and astrocytes. In fetal brain, expression is also strong in cells with the morphology of tanycytes and in the cell bodies of radial glia. Neurons are consistently negative. Pi isoenzyme thus localizes to the sites of the blood-CSF barrier, blood-brain barrier, CSF-brain barrier and pia-arachnoid-brain barrier. It is ideally placed to regulate neuronal exposure to potentially toxic substances derived from blood or cerebrospinal fluid. Expression so early in gestation is of significance and may imply a role in protection of the developing human brain.

Adult↗
PubMed1990

The ontogeny of human hepatic microsomal glucose-6-phosphatase proteins.

We have studied 250 human liver biopsy samples to determine the ontogeny of the microsomal glucose-6-phosphatase (EC 3.1.3.9) system. Human hepatic glucose-6-phosphatase enzyme activity develops at 11 weeks' gestation and slowly increases to approximately 10% of adult activity at term. In the first week after birth, activity rises to adult values. Increases in enzyme activity coincide with increasing concentrations of the glucose-6-phosphatase enzyme protein. The phosphate/pyrophosphate transport protein (T2) of the human hepatic glucose-6-phosphatase complex develops at a different rate from that of the enzyme. Our study shows that the development of rat and human glucose-6-phosphatase activities are completely different. We conclude that deficiencies of the proteins in the microsomal glucose-6-phosphatase complex can be diagnosed with much more certainty perinatally than prenatally.

Adult↗
PubMed1990

Lipid peroxidation and expression of copper-zinc and manganese superoxide dismutase in lungs of premature infants with hyaline membrane disease and bronchopulmonary dysplasia.

The putative involvement of reactive oxygen species in the etiology of lung damage in infants receiving mechanical ventilation has been examined by comparing the levels of peroxidation and expression of the antioxidant enzymes, CuZn and Mn superoxide dismutase, in lungs from control and affected infants as well as from fetuses and infants who died postnatally after term delivery. Mean levels (+/- SD) of lung peroxidation, determined with a thiobarbituric acid method, were similar in affected and control premature neonates and in fetal subjects (1.87 +/- 1.26, 1.92 +/- 2.07, and 1.19 +/- 1.36 nmol/mg protein, respectively). Expression of CuZn and Mn superoxide dismutases was also similar in these subjects and in the patients who died postnatally. Thus activity measurements and immunoblotting studies showed continuous expression of these enzymes throughout development with no apparent change in protein levels or size. Immunohistochemical examination of lung tissue showed expression of CuZn and Mn superoxide dismutases in epithelial, smooth muscle, endothelial, and some mesenchyme components. In patients with bronchopulmonary dysplasia, alveolar walls were thickened by an excess of fibrous tissue and terminal air spaces were lined mainly by type II pneumatocytes. All structures, including abnormal fibrous components, were positive for both CuZn and Mn superoxide dismutase. Our data show that, unlike some experimental animals, expression of at least these antioxidant enzymes in human infants born prematurely is similar to that in adults, and indicate that such infants are better adapted for life in an oxygen-containing environment than previously suspected.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchopulmonary Dysplasia↗
PubMed1989

The development expression of alpha-, mu- and pi-class glutathione S-transferases in human liver.

The developmental expression of the alpha, mu and pi class glutathione S-transferases has been defined in human liver using radioimmunoassay and immunohistochemistry. Expression of alpha and mu class isoenzymes increased significantly at birth, while that of the pi isoenzyme declined during the first trimester. Mu-class isoenzymes (GST1 1, GST1 2, GST1 2-1) were expressed in hepatocytes but not in other liver cell types.

Aging↗
PubMed1989

The enantioselective glucuronidation of morphine in rats and humans. Evidence for the involvement of more than one UDP-glucuronosyltransferase isoenzyme.

The formation of morphine glucuronides is enantio- and regioselective in rats and humans. In rat liver microsomes, natural (-)-morphine formed only the 3-O-glucuronide, whereas the unnatural (+)-morphine formed glucuronides at both the 3-OH and 6-OH positions, with the 6-O-glucuronide being the principal product. In human liver microsomes, both the 3-OH-and 6-OH positions were glucuronidated with each of the enantiomers, with the 3-O-glucuronide being the major product with (-)-morphine, and the 6-OH position preferred with the (+)-enantiomer. By using a series of biochemical and biological situations such as induction by xenobiotics, ontogeny, selective inhibition and genetic deficiencies, which are considered to be diagnostic of UDP-glucuronosyltransferase heterogeneity, we determined that two UDP-glucuronosyltransferase isoenzymes were responsible for the glucuronidation of morphine in rat liver. One isoenzyme (the so-called "morphine UDP-glucuronosyltransferase") was responsible for the glucoronidation at the (-)-3-OH and (+)-6-OH positions of morphine, whereas the other formed only the (+)-morphine-3-glucuronide. Evidence from enzyme induction and the genetically deficient deficient Gunn rat suggested that bilirubin UDPGT may be responsible for the (+)-morphine-3-UDP-glucuronosyltransferase activity. In human kidney, glucuronidation of both (-)- and (+)-enantiomers at the 6-OH position was deficient, whereas the activity at the 3-OH positions was still present, which indicated the involvement of two UDP-glucuronosyltransferases in the glucuronidation of morphine in man, as well as rats.

Age Factors↗
PubMed1989

Hepatic microsomal glucose-6-phosphatase system and sudden infant death syndrome.

Microassay techniques and monospecific antibodies were used to study the hepatic glucose-6-phosphatase system in liver samples from 55 infants who had died suddenly and unexpectedly, including 38 victims of sudden infant death syndrome (SIDS). Raised hepatic glycogen was found in 10, all of whom had a diagnosis of SIDS, and in 1 other infant who was already known to have type 1b glycogen storage disease (deficiency of transport protein T1). Of the 10 infants with raised hepatic glycogen who had a diagnosis of SIDS, 8 had glucose-6-phosphatase deficiency (type 1a glycogen storage disease), and 2 had transport protein T2 deficiency (type 1c glycogen storage disease).

Glucose-6-Phosphatase↗
PubMed1989

Differential expression of alpha and pi isoenzymes of glutathione S-transferase in developing human kidney.

Polyclonal antisera to the alpha and pi isoenzymes of glutathione S-transferase have been used in immunohistochemical studies to determine the developmental expression of these isoforms in human kidney. Before 35 weeks of gestation, both isoenzymes were expressed by the collecting tubules and developing nephrons. After this time, expression of the alpha set was restricted to the proximal tubule and that of the pi set to the distal and collecting tubules and the loop of Henle.

Adult↗