Search PubMed⌕ Search

Biomedical subjects

M M Thaler

Publications and source records attributed to M M Thaler.

At least 37 records · Page 2Linked to original sources
PubMed1985

Growth retardation in sickle-cell disease treated by nutritional support.

The effect of increased nutritional intake was evaluated in 5 growth-retarded children with sickle-cell disease. Growth on recommended daily calorie and protein intakes had been inadequate in all 5. Fat absorption and intestinal mucosal morphology were normal in all 5. 2 children were given nutritional supplementation by nasogastric intubation, 1 received nightly oral formula supplements, and 2 were supplemented with zinc, iron, folate, and vitamin E only. Nutritional supplementation by the nasogastric route produced a rapid sustained increase in growth rate, associated with striking reductions in pain crises and infections which had previously necessitated many hospital admissions. Oral supplementation improved the clinical course but had no effect on growth rate. Mineral and vitamin supplements influenced neither the growth rate nor the clinical course. The observations indicate that nasogastric nutritional supplementation may accelerate growth and reduce the incidence and severity of complications in growth-retarded children with sickle-cell disease.

Adolescent↗
PubMed1983

Cadmium, zinc, and copper metabolism in the mottled mouse, an animal model for Menkes' kinky hair syndrome.

Studies of uptake and release of 64Cu, 109Cd, and 65Zn in suckling C57BL/6J male mice revealed kinetics and distributions that differed for each metal both within and among the organs analyzed, suggesting distinct, albeit overlapping, mechanisms for transport and binding of each metal. In mutants, there were tissue-specific increases in copper-binding capacity. In hemizygotes (Moblo/y) accumulation of 64Cu was increased in kidney, lung, and duodenum. In heterozygotes (Moblo/+), 64Cu content was increased in kidney, with a smaller increase in lung, and no change in duodenal Cu. Decreased 64Cu accumulation was seen in liver in both hemi- and heterozygotes. In contrast, 64Zn and 109Cd accumulation in organs of heterozygote mice was not significantly distinguishable from normal. In skin and connective tissues there is excessive accumulation of 64Cu in Moblo/+ and Moblo/y, no abnormality in heterozygote 65Zn accumulation, but a clear decrease in heterozygote 109Cd content. In both mutant kidney and liver, there was an aberrant subcellular distribution of 64Cu, with the major fraction of sequestered 64Cu in the cytosol. Our studies establish that in spite of the ubiquity of metallothioneins and the structural similarities of those that have been characterized, there is specificity and functional heterogeneity in metal binding among tissues. The aggregate data suggest that there are unique regulatory mechanisms for the metabolism of copper and zinc, while there exists, in part, an inverse relationship between the binding of copper and cadmium. Our data further suggest that the blotchy mutation involves a specific cytosolic copper storage or transport protein also capable of binding cadmium.

Animals↗
PubMed1983

The proportion of mitochondrial isoenzyme of aspartate aminotransferase is not elevated in Reye's syndrome.

We reexamined a previously reported, highly specific increase in the relative proportion of the mitochondrial isoenzyme of aspartate aminotransferase (AST) in the serum of patients with Reye's Syndrome. Using ion exchange chromatography, we measured mitochondrial, cytosolic, and total AST in serum samples from (1) 10 patients early in the course of Reye's Syndrome; (2) nine controls with normal serum AST; and (3) seven controls with other diseases causing an increase in serum AST. The mitochondrial percentage (2.8 +/- 2.0%) in Reye's Syndrome was significantly lower (P less than 0.05) than that of both the normal control group (6.1 +/- 7.1%) and the group with increased AST (5.6 +/- 4.0%). We thus failed to confirm the previous report of a specific increase in the % of mitochondrial isoenzyme in Reye's Syndrome, and conclude that the % of mitochondrial isoenzyme is not likely to be a useful marker of (or predictor for progression to) Reye's Syndrome.

Adolescent↗
PubMed1982

Development and regulation of bile salt sulfotransferase in rat liver.

Hepatic bile salt sulfotransferase activity was extremely limited in fetus, gradually increasing after birth. At puberty, enzyme activity declined in males but not in females, suggesting the influence of gonadal hormones associated with sexual maturation. Extremely high enzyme activity was found in pregnant rats at term. The neonatal bile salt sulfotransferase activity could be stimulated by bile acid feeding during pregnancy or maternal bile duct ligation. In contrast, a decrease in enzyme activity was detected in the treated pregnant females. Phenobarbital treatment during pregnancy also produced a 5-fold increase in neonatal enzyme activity. These results suggested that bile salt sulfation was regulated by chemical factors before maturity, and by gonadal hormones thereafter. Two fractions with bile salt sulfotransferase activity were separated from female liver by zone electrophoresis and DEAE-Sephadex A-50 chromatography, while a single active fraction was detected in male liver which corresponded to one of the active female fractions. The two active fractions in the female exhibited the same molecular weight (130 000), and different isoelectric points (6.8 and 5.3). The male fraction had a molecular weight of 130 000 and a pI of 5.3.

Aging↗
PubMed1982

Generalized N-acetylneuraminic acid storage disease: quantitation and identification of the monosaccharide accumulating in brain and other tissues.

Brain and other tissues from a patient with extensive neonatal ascites and clinical symptoms suggestive of a severe neurovisceral storage disorder were examined following autopsy for the accumulation of oligosaccharides. This carbohydrate analysis revealed the presence of large amounts (3--21) mumol/g fresh weight) of sialic acid in brain, liver, and kidney tissue as the major abnormality. Exhaustive characterization of the accumulating material by gel filtration, gas-liquid chromatography, thin-layer chromatography, and GLC-mass spectrometry positively identified the saccharide as free N-acetylneuraminic acid. Based on the accumulation of only free N-acetylneuraminic acid in the tissue of this patient, and normal activities of lysosomal enzymes involved in the catabolism of cellular glycoproteins, this storage disorder appears to result from a previously unreported defect in glycoconjugate metabolism.

Brain↗
PubMed1981

Primary intestinal lymphangiectasia. Case report with radiological and ultrastructural study.

A 16-year-old boy with primary intestinal lymphangiectasia presented with peripheral edema of 6 weeks duration. Laboratory and radiological studies included absolute lymphopenia, hypoalbuminemia, steatorrhea, abnormal stool 51Cr-albumin value, edema of small intestinal folds, dilated mesenteric lymphatics, as well as bilateral filling defects in external and common iliac lymph nodes. Abdominal CT scan revealed a possible periaortic mass. Small intestinal biopsies demonstrated normal villous architecture with dilated lacteals, and electron microscopy revealed enterocytes with normal as well as blunted microville, enlarged, dilated lacteals and intercellular vacuoles. An exploratory laparatomy was performed and revealed no masses but dilated serosal lymphatic vessels. Medical treatment, including marked restriction of long chain triglyceride intake, resulted in loss of peripheral edema, weight stabilization, and normal activity.

Adolescent↗
PubMed1981

Liquid-chromatographic determination of bilirubin and its conjugates in rat serum and human amniotic fluid.

This newly developed and highly specific and sensitive procedure was applied to the determination of unconjugated bilirubin and its ester conjugates in rat serum and human amniotic fluid. Bilirubin conjugates in biological samples are converted to methyl esters by alkaline methanolysis, extracted into chloroform, and the unconjugated bilirubin and esterified pigment derivatives are fractionated by "high-performance" liquid chromatography. The separated pigments are measured spectrophotometrically. Bilirubin and its mono- and di-conjugates are readily quantitated, even in previously undetectable concentrations. Linearity was established from 0.07 to 121.2 mumol/L for unconjugated bilirubin, 0.07 to 34.6 mumol/L for the C-8 monoconjugate, 0.06 to 69.3 mumol/L for the C-12 monoconjugate, and 0.17 to 43.7 mumol/L for the di-conjugate fraction. The detection limit was 0.03 mumol/L for unconjugated bilirubin and for each monoconjugate, and 0.1 mumol/L for the di-conjugated pigment.

Amniotic Fluid↗
PubMed1980

Responses of rat and chick chondrocytes and rate hepatoma cells to plasma fractions with insulin-like and growth-promoting activities.

Plasma protein Cohn fraction IV-1 was extracted and fractionated according to the method of Van Wyk et al.[1], with the omission of the Sephadex G-75 step. The fractionated polypeptides were investigated for insulin-like activity (lipid synthesis and lactate production) and growth-stimulatory activity (DNA synthesis) in three bioassay systems: rat hepatoma cells, and rat and chick chondrocyte suspensions. Binding of each fraction to insulin receptors in isolated plasma membranes was also determined. Three peptide subfractions, with molecular weights ranging from 400 to 20 000, stimulated lipid synthesis, lactate production and DNA synthesis in all three bioassay systems. There were distinct species- and cell-type-specific variations in the quantitative patterns produced by each subfraction. In contrast, authentic insulin (0.005-0.1 ng/ml) had no effect on DNA and lipid synthesis anad lactate production in hepatoma cells and chondrocytes. One of the three active subfractions and two relatively inactive fractions displaced insulin from its receptors. These observations indicate that acid-ethanol extracts of plasma contain a variety of peptide factors with insulin-like and growth-promoting effects whose expression in different cell types is modulated by inherent properties of each cell type which are determined genetically presumably. Surface receptors for authentic insulin do not appear to play an essential role in the insulin-like activities of the isolated plasma fractions.

Animals↗
PubMed1980

Growth-modulating tripeptide (glycylhistidyllysine): association with copper and iron in plasma, and stimulation of adhesiveness and growth of hepatoma cells in culture by tripeptide-metal ion complexes.

The tripeptide H-Gly-His-Lys-OH (GHL) is a human plasma constituent which has been previously shown to modulate the growth and viability of a variety of cell types and organisms. Experimental observations presented herein indicate that GHL is complexed with the transition metal ions Cu++ and Fe++ in vivo and may exert its biological effects as a peptide-metal chelate. At physiological pH in vitro, GHL associates with ionic copper, cobalt, iron, molybdenum, manganese, nickel, and zinc, but has no affinity for calcium, manganese, potassium, and sodium. GHL acts synergistically with copper, iron, cobalt, and zinc to alter patterns of cell growth in monolayer cultures of a tumorigenic hepatoma cell line (HTC4). These transition metals induce cellular flattening and adhesion to support surfaces, and inhibit DNA synthesis and lactic acid production when growth is limited by reduction of serum concentrations in medium. These inhibitory effects are neutralized, and intercellular adhesion and growth are stimulated by GHL in medium at nanomolar concentrations. Cu and Fe are the most active metals when combined with GHL. The results suggest that the inability of HTC4 cultures to replicate without adequate concentrations of serum in medium may reflect deficiency of GHL and transition metals, which appear to form complexes prior to interaction with cells. Chelation of transition metals with GHL and, potentially, with other growth-modulating peptide factors in plasma or medium, may provide a mechanism for expression and regulation of biological activities influenced by transition metals and polypeptide growth factors. The observed effects of GHL-metal complexes, including stimulation of cellular adhesiveness to substratum (flattening) and intercellular attachment (monolayer formation), appear to satisfy requirements for growth of hepatoma cells in monolayer culture.

Carcinoma, Hepatocellular↗
PubMed1980

Fatty acids, fibrinogen and blood flow: a general mechanism for hyperfibrinogenemia and its pathologic consequences.

Plasma fibrinogen is elevated in various stressful states and conditions in which active mobilization of free fatty acids (FFA) occurs. Reduction of plasma FFA by an assortment of hypolipidemic drugs is consistently followed by a decrease in the accompanying hyperfibrinogenemia. A direct link between FFA and fibrinogen has been demonstrated in animals, and in experiments employing incubated liver slices. Based on these clinical and experimental observations, we postulate that hepatic fibrinogen synthesis is stimulated by FFA. Since fibrinogen is a major determinant of whole blood viscosity, erythrocyte aggregation, and sludging of red cells in terminal and pre-terminal blood vessels, we propose that microcirculatory blood flow may be impaired in the presence of chronically elevated plasma FFA levls. Consequently, hypolipidemic drugs may be effective in prevention of circulatory complications associated with FFA-induced hyperfibrinogenemia.

Blood Flow Velocity↗
PubMed1980

Improved recovery of somatomedin activity from plasma by prolonged formic acid extraction.

Recovery of somatomedin activity from plasma fractions was increased approximately 5-fold by prolonged extraction of isolates with formic acid. Extraction for 72 hours enhanced the yields of active peptides in the 6,000, 8,000 and > 20,000 dalton range. Yields of smaller peptides were similar following short (2 hrs) and long (72 hrs) extraction periods. Active fractions obtained after prolonged extraction possessed sulfation activity and insulin-receptor affinity comparable to somatomedin isolated during short extraction with formic acid.

Animals↗
PubMed1980

Intractable diarrhea of infancy due to intestinal coccidiosis.

Intestinal coccidiosis in a 6-mo-old infant terminated fatally after 30 wk of continuous total parenteral nutrition, and proved refractory to treatment with antibiotics, hydrocortisone, and antimetabolic agents. Intestinal biopsies obtained at laparotomy revealed flattened mucosa infiltrated with coccidia at various stages of the parasites' life cycle. The course was characterized by severe diarrhea due to a cholera-like hypersecretion of intraluminal fluid. This case suggests that intestinal coccidiosis may be included among the small number of conditions responsible for authentic "intractable diarrhea of infancy."

Coccidiosis↗
PubMed1979

Effect of transition metals on recovery from plasma of the growth-modulating tripeptide glycylhistidyllysine.

Isolation and purification of growth-modulating peptides from biological sources is often accompanied by excessive losses of bioactive material. During the isolation of a growth-modulating tripeptide glycylhistidyllysine (GHL) from human plasma, copper and iron were found to co-isolate with the peptide. Studies with [3H]GHL demonstrated that these metals interfere at several steps of the procedure for the isolation of GHL from plasma (gel filtration chromatography, high-pressure silica-gel). Removal of these metals with an insoluble chelating resin (Cellex 100) enhanced recovery of [3H]GHL from plasma 8-fold. These results suggest that removal of transition metals may aid in the recovery of peptides which are difficult to isolate from biological sources.

Chelating Agents↗