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Biomedical subjects

J Metz

Publications and source records attributed to J Metz.

At least 91 records · Page 5Linked to original sources

Behavioral and subjective effects of ethanol: relationship to cerebral metabolism using PET.

This study examined the effects of ethanol on regional cerebral metabolic rate using positron emission tomography (PET). The study explored the relationship between the mood-altering effects of ethanol and its effects on regional cerebral glucose utilization (CMRglu) in eight healthy male volunteers. In the first phase of the study, the subjects participated in a behavioral preference procedure conducted in a recreational environment to determine their responses to ethanol (0.5 g/kg) in a naturalistic setting. They then participated in three PET sessions, receiving at three to seven day intervals, in counterbalanced order, placebo, 0.5 g/kg or 0.8 g/kg ethanol. PET scans were conducted using a PETT-VI scanner with F-18-2-fluoro-2-deoxyglucose (FDG) as the tracer. The mood-altering effects of ethanol were measured in both the naturalistic and the PET phases of the study. Ethanol produced comparable effects on mood in the naturalistic and the PET settings (i.e., increases in positive mood). The lower dose of ethanol produced variable effects on whole brain and regional CMRglu across subjects. There was some suggestion that certain regional metabolic changes after ethanol were correlated with subjective responses to the drug. The higher dose of ethanol decreased whole brain CMRglu in most subjects. All regions were affected about equally. It was concluded that the mood-altering effects of ethanol are not related in a simple manner to regional changes in CMRglu.

Adult↗

Autistic children and their first-degree relatives: relationships between serotonin and norepinephrine levels and intelligence.

Whole-blood serotonin (5-HT) and plasma norepinephrine (NE) were studied in 16 autistic children, 21 siblings of autistic children, and 53 parents of autistic children. Both plasma NE and whole-blood 5-HT were negatively correlated with vocabulary performance. Whole-blood 5-HT and plasma NE did not differ between autistic children with or without histories of self-injurious behavior or decreased pain sensitivity. Eighteen subjects were hyperserotonemic (whole-blood 5-HT greater than 270 ng/ml). For these subjects, plasma NE was significantly higher than for subjects without hyperserotonemia. Seven of 10 families with one hyperserotonemic member had two or more hyperserotonemic members. Observations of familiarity of whole-blood 5-HT suggest that larger-scale and more focused study of whole-blood 5-HT as a possible genetic marker may be productive.

Adolescent↗

Investigations of the antiatherosclerotic effect of the thromboxane A2 receptor antagonist Daltroban.

In the pathogenesis of atherosclerosis an accumulation of lipids, predominantly in the form of cholesteryl esters within the blood vessel wall is observed. Interaction of the plaques, e.g. with platelets, is suggested to contribute considerably to their growth. Compounds affecting both processes should prevent atherosclerotic progression and therefore are of great interest for potential therapeutic use. We investigated the effect of Daltroban, which has been characterized as a selective thromboxane receptor antagonist with platelet inhibiting activity, in two models: 1) cholesterol metabolism in liver cells and 2) progression of atherosclerosis in aorta of hypercholesterolemic rabbits. Daltroban reduced 14C-acetate incorporation into cholesteryl esters stronger than into cholesterol in rat hepatocyte monolayer cultures. In male white New Zealand rabbits fed 0.5% cholesterol enriched diet for 96 days, coadministration of Daltroban beginning at the 42th day on diet reduced aortic cholesterol content, plaque covered surface of aortic wall, and lumen stenosis by plaques more than 30 percent. The significant inhibition of the progression of atherosclerosis in the hypercholesterolemic rabbits by Daltroban is suggested to be effected by both inhibition of cholesterol metabolism as well as of platelets.

Animals↗

Interrelationship between serum concentrations of methionine, vitamin B12 and folate.

The metabolism and intracellular recycling of methionine requires vitamin B12 as cofactor and methyltetrahydrofolate as coreactant. To examine the interrelationship between serum levels of methionine, vitamin B12 and folate, serum methionine levels were assayed in patients with reduced levels of these vitamins and in healthy subjects. Approximately half the patients with either vitamin B12 or folate deficiency, and more than half those with combined deficiency, had methionine levels below the reference range (37-136 mumol/l). There was no correlation between vitamin B12 or folate and serum methionine levels within the healthy group. There was also no correlation within the group with low folate levels. Within the vitamin B12 deficient group on the other hand, the correlation was highly significant (r = 0.547, p less than 0.001). The finding that many patients with vitamin B12 or folate deficiency have normal serum levels of methionine suggests a significant role for other factors such as betaine-dependent methionine synthesis in the maintenance of serum methionine concentrations.

Adult↗

Both valine and isoleucine supplementation delay the development of neurological impairment in vitamin B12 deficient bats.

Supplementation of the diet with valine or isoleucine protects the fruit bat from neurological impairment associated with experimentally induced vitamin B12 deficiency. Valine and isoleucine are precursors in the vitamin B12 dependent propionic acid pathway and it is proposed that they exert their protective effect through stimulation of this pathway. This suggests that the previously observed protective effect of methionine may be mediated also through this pathway, since methionine may be metabolised via the transsulfuration pathway to propionyl CoA. The results of this study refocus attention on the propionic acid pathway, and specifically on the methylmalonyl CoA mutase reaction, as central to the biochemical basis of the vitamin B12 neuropathy.

Animals↗

Monitoring the voluntary fortification of maize meal with riboflavin and nicotinamide.

To combat vitamin deficiencies in populations whose dietary staple is maize, the fortification of maize meal with riboflavin and nicotinamide has been recommended. Subsequently, part of the milling industry has voluntarily fortified the meal with these two vitamins. In the present study, the concentrations of added riboflavin and nicotinamide were determined by high-performance liquid chromatography in 43 samples from a wide area. With the exception of three samples, concentrations of these vitamins were below the recommended level, and most were less than half this amount. Fortification programmes require regular monitoring by an independent authority.

Avitaminosis↗

Evaluation of the effectiveness of AIDS training and information courses.

Acquired immunodeficiency syndrome (AIDS) is considered to be the major health threat of the 20th century. The only way to contain the spread of AIDS is by prevention of infection in the first place. This task is essentially one of education. Because the South African Institute for Medical Research is traditionally associated with the prevention of infectious diseases, an AIDS Centre was established to promote education. As part of the launching of the Centre in January 1988, a series of four 1-day courses was held for different target groups. Attendance rates were high and all participants completed a pre- and post-test questionnaire designed to evaluate the effectiveness of the courses and identify existing level of knowledge, present needs and possible future demands. Collected data were examined by correlation analysis, the chi-square test and the t-test. Results generally showed improved changes in knowledge and attitudes about AIDS, and pointed the way forward for future education interventions in the community.

Acquired Immunodeficiency Syndrome↗

Heart innervation after ligation of the left anterior descending coronary artery (LAD).

Distribution and amount of neuropeptide Y- and synaptophysin-immunoreactive nervous structures within the heart were investigated in dogs 4 days after ligation of the left anterior descending coronary artery (LAD). In the right atrium and posterior left ventricular regions, which were taken as (non-infarcted) control areas, neuropeptide Y-immunoreactive paravascular nerves and a perivascular nerve plexus running within the adventitia of the coronary arteries and their branches down to the arterioles were observed. Morphometric measurements of the area density revealed 0.099 +/- 0.014% for synaptophysin- and 0.037 +/- 0.0072% for neuropeptide Y-immunoreactivity within the posterior wall of the left ventricular myocardium. Four days after ligation of the LAD only single synaptophysin- and neuropeptide Y-immunoreactive nerve fibers were very rarely detected in the infarcted region of the anterior wall of the left ventricle. Above the ligature larger than normal neuropeptide Y-immunoreactive axons within nerves along the LAD indicated a blockage of the axoplasmic transport of this peptide. When investigating this model of experimental myocardial infarction, mechanical traumatization of peri- and paravascular nerves of the LAD by the ligature has to be considered as a major pathogenetic factor, in addition to ischemia leading to denervation of infarcted as well as non-ischemic myocardium.

Animals↗

Computer-assisted morphometric study of the innervation of the guinea pig heart.

A computer-assisted method is introduced for the morphometric analysis of immunoreactive markers of the innervation of the heart, such as synaptophysin, neuropeptide Y (NPY), neurotensin (NT), substance P (SP), and calcitonin gene-related peptide (CGRP). Video images of stained sections were digitalized and the area density (AD) of the immunoreactive structures was measured by discrimination for grey levels within the myocardium of the right atrium, the perivascular region of epicardial arteries, and the trunk of the bundle of His. Synaptophysin immunoreactivity (IR), which served as a marker for presynaptic vesicles, indicated a dense innervation of the conductive system (AD 1.5241). Marked differences in the pattern of distribution were found between the neuropeptides. The AD of NPY-IR (0.5073) and SP-IR (0.1352) was highest in the perivascular tissue, while NT-IR (0.1628) and CGRP-IR (0.5161) exhibited maximal values in the bundle of His. The computer-assisted morphometric measurement of the AD of immunoreactive markers is suggested to be a suitable method for quantitative studies of the innervation of the heart under normal and experimental conditions.

Animals↗

Thiamine deficiency in black male hostel-dwellers. The need for thiamine supplementation of sorghum beer.

Some indices of nutrition have been examined in hostel- and non-hostel-dwelling groups of industrially employed black males. Hostel-dwellers in the large metropolitan areas have to prepare their own food and many are accustomed to excessive alcohol intake, especially of sorghum beer. In the two groups studied, blood levels of vitamin B12, folate, pyridoxal and albumin were similar, but erythrocyte thiamine levels were significantly lower in the hostel-dwellers. Although the proportion of subjects with elevated levels of gamma-glutamyltransferase, an index of alcoholic liver disease, was similar in the two groups, thiamine-deficient hostel-dwellers had a greater proportion of elevated values suggesting that thiamine deficiency was related to both inadequate diet and excessive alcohol consumption. Fortification of sorghum beer with thiamine might prevent or reduce thiamine deficiency in this group. The cost would not materially affect the price of the beer.

Adult↗

Vasoactive intestinal polypeptide immunoreactivity in the spinal cord of the guinea pig. A mapping study.

The distribution of vasoactive intestinal polypeptide-immunoreactive (VIP-IR) neurons in the lower medulla oblongata and the spinal cord has been analyzed in guinea pigs. This study includes results obtained by colchicine treatment and transection experiments. In the spinal cord, numerous VIP-IR varicosities were observed in the substantia gelatinosa of the columna dorsalis; some were also found in the substantia intermedia and the columna anterior. The spinal VIP-IR nerve fibers were mainly of intraspinal origin and oriented segmentally. VIP-IR nuclei in the spinal cord extended dorsally into corresponding regions of the caudal medulla oblongata, namely from the substantia intermedia medialis and lateralis into the vagus-solitarius complex and from the nucleus spinalis lateralis into the area of the nucleus reticularis lateralis. Additional VIP-IR perikarya were observed in the pars caudalis of the nucleus spinalis nervi trigemini. The VIP-IR nuclei within the caudal medulla oblongata probably form a continuous system with those localized within the spinal cord. They may be involved functionally in the modulation of cardiovascular and respiratory regulation in the guinea pig.

Animals↗

Drug-induced intrahepatic cholestasis: characterization of different pathomechanisms.

The pathogenesis of intrahepatic cholestasis in rats was studied using isolated perfused livers as an experimental model. Three basic mechanisms were differentiated: Permeabilization of the bilio-sinusoidal barrier associated with electron microscopic alterations of the tight junctional complexes was found in livers of rats treated with alpha-naphthylisothiocyanate (ANIT, 250 mg/kg body weight). Consequences of these alterations were: reflux of bile constituents such as taurocholate and sulfobromophthalein and increased access to the biliary space of paracellular markers such as inulin and sucrose. The clear-cut mechanism of ANIT cholestasis was used to distinguish other mechanisms of intrahepatic cholestasis. Inhibition of the basic process of fluid secretion was found to be the primary event in the development of cholestasis induced by estrogens. After 5 days of treating rats with ethinyl estradiol (5 mg/kg/day), bile flow was diminished in isolated livers while the permeability of the biliary tract to sucrose and inulin was not affected. Accordingly, the maximal concentration of taurocholate in bile was increased, indicating that its secretion was sustained. The same effect was observed after 1 week of treatment with the depot estrogen estradiol valerate (1 mg/kg/week). After 3 weeks of treatment, however, the taurocholate concentration in bile was lowered and the clearance of sucrose was increased. Bile flow remained at the same cholestatic level for 20 weeks. These results suggest that estrogens have the potency to increase tight junctional permeability only in a second step in the development of cholestasis, following the inhibition of bile flow. An additional mode of secretory inhibition was induced by lowering the concentration of Ca2+ in the perfusate of isolated liver.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Naphthylisothiocyanate↗

Immunohistochemical localization of glucagon-like peptide 1. Use of poly- and monoclonal antibodies.

We report the use of poly- and monoclonal antibodies to study the immunohistochemical distribution of glucagon-like peptide-1 immunoreactivity (GLP-1-IR) in various tissues. The polyclonal antibodies against GLP-1 reacted with pancreatic A cells, enteroglucagon (L) cells in the gut, and some neurons in the central nervous system of all species tested. In pancreas and gut the monoclonal antibodies against GLP-1 exhibited a similar, but species specific distribution, relative to the polyclonal antibodies. The colocalization of GLP-1 and glucagon immunoreactivity in pancreatic, intestinal, and nervous tissues is in agreement with previously reported findings that both peptides are part of a single precursor molecule (preproglucagon).

Amino Acid Sequence↗