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Biomedical subjects

J Metz

Publications and source records attributed to J Metz.

At least 109 records · Page 6Linked to original sources

The fruit bat as an experimental model of the neuropathy of cobalamin deficiency.

The fruit bat provides a unique small mammal model of the neurological changes associated with cobalamin deficiency. Work with this model has shown that methionine moderates the development of the neurological impairment. This action does not appear to be via the methyl donor S-adenosylmethionine, but its role in the provision of formate is not excluded. Furthermore, methylation reactions in the nervous system are not impaired in severe cobalamin deficiency, despite low levels of methionine synthetase activity. The accumulation of physiologically inactive analogues of cobalamin also do not appear to be aetiologically important in the neuropathy. Brain folates are minimally affected by severe cobalamin deficiency, although liver folates decrease significantly. Deranged GABA function in the brain may play a role in the symptomatology of cobalamin deficiency. There is some evidence for the hypothesis that deranged fatty acid metabolism in neural tissue contributes to altered membrane structure and hence function. Changes in the properties of membrane proteins may play a contributory role. The biochemical basis of the neuropathy has still to be fully elucidated.

Animals↗

Neurotensin in the human brain.

The localization of neurotensin-immunoreactive sites in the adult human brain was investigated by the indirect immunoperoxidase method of Sternberger [Sternberger (1979) Immunocytochemistry. Wiley, New York]. Our results demonstrate a widespread, albeit uneven occurrence of neurotensin-immunoreactive cells and processes throughout the central nervous system. Immunoreactive cells are prominent in the medial hypothalamus and in various regions of the limbic system, including the amygdaloid body, septal area, bed nucleus of the stria terminalis and piriform cortex. A few cells were also found in the dorsal synencephalon, superior colliculus, periaqueductal grey and spinal trigeminal nucleus. The distribution of immunoreactive fibres corresponds well with that reported for rodents. Areas with the highest concentration of neurotensin-immunoreactive processes included all the areas where immunoreactive neurons were found and, in addition, periventricular thalamic nuclei, the sublenticular region, lateral parts of the brainstem reticular formation and the vagus-solitarius complex. Comparison mapping studies of melanin-containing neurons on sections treated with neurotensin antiserum revealed an anatomical relation between almost all the catecholaminergic cell clusters with peptide-containing fibres.

Brain↗

Tissue folates in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency and neurological impairment.

1. Long-term exposure of the fruit bat Rousettus aegyptiacus to nitrous oxide, which inactivates methylcobalamin, leads to neurological impairment and ataxia. 2. In N2O-exposed animals, liver concentrations of total folates and methyl folates decreased to less than one-fifth that of control animals. Pediococcus cerevisiae-active folates were also reduced. 3. In brain, there were no changes in total or methyl folates, but P. cerevisiae-active folates were lower in N2O-exposed animals. 4. Supplementation with methionine retarded the development of neurological impairment and the fall in liver total and methyl folates, but not that in P. cerevisiae-active folates. 5. Supplementation with serine failed to retard the development of neurological impairment or fall in hepatic folates. 6. The present results suggest that the N2O-induced neurological impairment in the bat is not related to depletion of cerebral folates, but do not exclude changes in the subcellular distribution of folates.

Animals↗

Iron, folate and vitamin B12 nutrition and anaemia in black preschool children in the northern Transvaal.

The prevalence of anaemia and deficiencies of iron, folate and vitamin B12 were investigated in 140 rural black preschool children aged 3-5 years living in five different villages in the Letaba area, near Tzaneen. Anaemia was highly prevalent, 39.2% of the children having haemoglobin levels below 11.1 g/dl. Approximately 10% were considered to be iron-deficient. On the basis of subnormal red cell folate values, 1 in 4 children was folate-deficient, suggesting the need for intervention at the community level such as enrichment of the staple foodstuff, maize meal, with folic acid.

Black or African American↗

Distribution of calcitonin gene-related peptide-like immunoreactivity in the guinea pig heart.

The distribution of calcitonin gene-related peptide like-immunoreactivity (CGRP-IR) within the heart and adjacent blood vessels of the guinea pig was investigated immunohistochemically by use of the peroxidase-antiperoxidase (PAP) technique. Numerous paravascular and perivascular immunoreactive nerve fibers were localized around the aorta, coronary arteries and their branches down to the terminal vasculature. Arterioles in the atria showed greatest density of immunoreactive varicosities of all blood vessels. The epicardium, endocardium and the conductive system also contained numerous CGRP-IR nerve fibers. In the myocardium the number of immunoreactive varicosities was variable. Many were present in both atria, moderate amounts were seen in the right ventricle and parts of the intraventricular septum, and only a few occurred in the left ventricle. CGRP-IR was infrequently found within intracardial ganglionic cells but was abundantly distributed in the surrounding nerve fibers.

Animals↗

Distribution of synaptophysin immunoreactivity in guinea pig heart.

The distribution of synaptophysin, an integral polypeptide of presynaptic vesicle membranes, was investigated in guinea pig heart by immunohistochemistry using monoclonal antibodies. Synaptophysin immunoreactivity was found in varicose nerve terminals in all regions of the heart. Dense networks of immunoreactive varicosities were found to surround the vasculature and to be located within the subendocardial layers of the atria and ventricles, the highest levels being seen in the innervation of the conductive system. As synaptophysin is probably a component of the presynaptic vesicles of all synapses, its use as a marker of all nerve terminals within the heart is proposed.

Animals↗

Dissociation of methionine synthetase (EC 2.1.1.13) activity and impairment of DNA synthesis in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency.

1. The effect of methylcobalamin inactivation by the anaesthetic gas nitrous oxide on the activity of the cobalamin-dependent methionine synthetase (5-methyltetrahydrofolate homocysteine methyltransferase; EC 2.1.1.13) reaction, and on DNA synthesis, in the fruit bat Rousettus aegyptiacus, was examined. 2. Methionine synthetase activity in the liver of bats exposed to N2O-oxygen (50:50, v/v) for 90 min/d averaged 32% of that of controls after 4 d of exposure and only 5% after 12-14 weeks of exposure. 3. DNA synthesis in the bone marrow, as reflected by the deoxyuridine suppression test, was unaffected by 4 d of exposure to N2O and only minimally affected after 5-10 weeks of exposure. 4. These results suggest that DNA synthesis in the fruit bat is unusually resistant to inhibition of methionine synthetase and imply the existence of a non-methylated circulating folate pool in this species.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Serum vitamin B12 binders in South African blacks with hepatocellular carcinoma.

Sera from 242 South African blacks with hepatocellular carcinoma were assayed for unsaturated vitamin B12 binding capacity (UBBC) and vitamin B12 activity. Six patients were younger than 20 years of age, and 24% were younger than 30 years of age. Eighty-four percent of the patients had a slightly raised UBBC and 86% had a slightly elevated vitamin B12 value, but in no patient was an exceptionally high UBBC present. Serum UBBC and vitamin B12 were not higher in younger patients, and raised UBBC values were not related to serum alpha-fetoprotein values. Serum UBBC and vitamin B12 concentrations were not significantly different in patients with and without coexisting cirrhosis. In none of the patients with a UBBC above 3000 pg/ml was the fibrolamellar variant of hepatocellular carcinoma present. The authors conclude that South African blacks with hepatocellular carcinoma do not secrete an abnormal vitamin B12 binding protein.

Adolescent↗

Studies of the guinea-pig epididymis. III. Innervation of epididymal segments.

The innervation of the ductuli efferentes and seven zones of the guinea-pig epididymis was investigated using immunohistochemical, histochemical and electron-microscopical techniques. Nerve fibers were localized by use of antibodies against substance P (SP-IR), vasoactive intestinal polypeptide (VIP-IR) and dopamine-beta-hydroxylase (DBH-IR). In the ductuli efferentes and all zones of the epididymal duct, SP-IR is consistently observed in the interstitial tissue and perivascular areas. Histochemistry reveals a significant amount of acetylcholinesterase-containing fibers in the interstitial, perivascular and periductal smooth muscles of the ductuli efferentes and zones V, VI and VII. In contrast to the homogeneous distribution of SP-IR within all zones of the epididymis, VIP-IR is seen only in zones VI and VII. Within these zones, VIP-IR is detected in large amounts in the subepithelial and muscular layers as is a sparse number of SP-IR varicosities. DBH-IR is also seen throughout all zones in the interstitial and perivascular regions with a tendency to increase in zones VI and VII. Transmission electron microscopy (TEM) reveals evidence of a cholinergic (agranular vesicles, AGV), adrenergic (small granular vesicles, SGV) and peptidergic (large granular vesicles, LGV) innervation throughout the interstitial connective tissue of the ductuli efferentes and all epididymal zones. Furthermore AGV are localized in the subepithelial layer, and also co-stored with LGV in the muscular layer of zones VI and VII. No nerve profiles were encountered within the epithelium. A correlation of immunohistochemical findings to TEM counterparts as well as their possible functional role are discussed.

Animals↗

Permeability studies of the guinea pig placental labyrinth. II. Tracer permeation and freeze-fracture of fetal endothelium.

Permeability of the fetal endothelium within the guinea pig placental labyrinth is studied by means of horseradish peroxidase (HRP) and ionic lanthanum as diffusion tracers. The paracellular transport of HRP is restricted by the occluding junctions of the fetal endothelium. In contrast, ionic lanthanum readily permeates most of the intercellular junctions and rapidly infiltrates the basal lamina. Freeze-fracture replicas reveal zonulae occludentes connecting the fetal endothelial cells. The network of the zonulae occludentes is variable, exhibiting highly complex areas as well as single strand interconnections. A correlation between the permeability studies and freeze-fracture findings is discussed.

Animals↗

Detection of glucagon in pancreatic A-cells by monoclonal antibodies.

The production of a mouse monoclonal antibody from a hybrid myeloma and its use for the detection of glucagon in tissue sections is reported. The hybrid clone isolated after fusion of mouse myeloma cells with hyperimmune spleen cells from a mouse previously immunized with porcine glucagon allowed us a standardized and permanent source of monoclonal antibodies in a culture cell system. The monoclonal antibody (3 GL 31) specifically reacts with pancreatic A-cells in several species including pig, rabbit, tupaia belangeri and sheep. No immunoreactivity is observed against gut cells and neurons.

Animals↗

Plasma amino acids and tissue methionine levels in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency.

The effect of methylcobalamin inactivation by the gas nitrous oxide on plasma amino acid and tissue methionine levels in fruit bats (Rousettus aegyptiacus) was examined. Animals exposed to N2O-oxygen (1:1, v/v) for 90 min daily received a fruit diet with or without methionine or betaine supplements. Exposure and diets were continued for up to 17 weeks or until neurological impairment and muscular weakness was established. All the groups exposed to N2O had significantly lower liver, brain and plasma methionine concentrations except the methionine-supplemented animals which showed significantly raised levels. Plasma homocysteine, which was absent in controls, was present in all the N2O-exposed groups. Betaine supplementation resulted in reduced accumulation of homocysteine in plasma. However, plasma and liver methionine levels were only slightly increased compared with animals on the basal diet, and brain methionine levels were the lowest of all the groups studied. These results support the hypothesis that reduced methionine synthesis is an important contributor to the development of neurological impairment in this species and suggest that dietary supplementation with the methionine precursor betaine cannot replace the loss of vitamin B12-dependent methionine synthesis.

Amino Acids↗

A sex difference in serum cobalamin and transcobalamin levels.

In healthy young adults, serum levels of cobalamin, unsaturated and total cobalamin binding capacity, and transcobalamin (TC) II are significantly higher in females, while TC III is higher in males. These findings have relevance to the reference values in normals for these tests.

Adolescent↗

Intestinal absorption of thiamin from yeast-containing sorghum beer.

The rate of absorption of 14C-thiamin added to sorghum beer has been studied in isolated loops of rat duodenum and adjacent jejunum. Appreciable amounts of the vitamin were absorbed in spite of the presence in the beer of alcohol and live yeast cells avid for the vitamin. These results suggest that commercially brewed sorghum beer, a beverage consumed widely by Third World populations, can be fortified with thiamin to prevent the development of deficiency of the vitamin in habitual consumers of the beer.

Animals↗

Fortification of sorghum beer with thiamin.

The consumption of indigenous cereal-based fermented beer is widespread throughout Africa and other parts of the world. In some countries such beer is brewed commercially as well as at home. As evidence of beri-beri may occur in habitual consumers of the beer, the thiamin content of beer brewed commercially from a mixture of sorghum and maize was investigated. Thiamin concentration in beer averaged 0.33 mg/l, with more than 95% in the cellular fraction, mainly live yeast cells. The thiamin in the cells is not generally available for absorption and the cells take up thiamin added to the beer. At low concentrations (0.25-0.5 mg/l) up to 90% of added 14C-thiamin was taken up by the cells but with concentrations in excess of 2.5 mg/l, the uptake was less than 30%. These results indicate that fortification of sorghum beer with thiamin is feasible. The addition of 2.5 mg/l would supply up to 1.6 mg of absorbable thiamin and thus meet the recommended daily allowance in the target group of habitual consumers.

Beer↗