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Biomedical subjects

M A Thomas

Publications and source records attributed to M A Thomas.

At least 109 records · Page 6Linked to original sources
PubMed1990

Hereditary nephritis in the bull terrier: evidence for inheritance by an autosomal dominant gene.

A high prevalence of renal failure has been reported in bull terriers in Australia. The pattern of inheritance was analysed in a family of 33 bull terriers in which 10 dogs had renal disease manifested by proteinuria, ultrastructural abnormalities in the glomerular basement membrane, renal failure, or 'end stage' kidneys. The presence of at least one affected parent for each affected offspring, the approximately equal male/female ratio and the apparent absence of 'generation-skipping', strongly supported an autosomal dominant mode of inheritance, assuming a fully penetrant single major gene locus. Further evidence was not compatible with either an autosomal recessive or X-linked inheritance pattern. This contrasts with the X-linked inheritance shown in Alport's-type human hereditary nephritis and hereditary glomerulopathy in the samoyeds. Hereditary nephritis in the bull terrier should be a useful model for non-Alport's-type human hereditary nephritis, which is also reported to have an autosomal dominant inheritance pattern.

Animals↗
PubMed1990

Metallothionein genes from the flowering plant Mimulus guttatus.

In response to excess metal, higher plants produce metal-binding peptides [( gamma EC]nG) whose biosynthesis is believed to be mediated by enzymes involved in glutathione (gamma ECG) metabolism. In contrast, animals synthesize metallothioneins, gene-encoded low molecular weight cysteine-rich metal-binding proteins. In an investigation of copper-regulated genes in the copper-tolerant flowering plant Mimulus guttatus, we have isolated a series of cDNA clones identifying two genes which encode a protein with class I metallothionein domains. This represents the first description of a metallothionein gene in a flowering plant.

Cloning, Molecular↗
PubMed1990

Halothane-induced functional and structural modifications in sarcoplasmic reticulum membranes from pig skeletal muscle.

We investigated the effect of halothane on lipid and protein components of sarcoplasmic reticulum membranes isolated from pig trapezius muscle. We studied the relationships between the (Ca2(+)-Mg2+)-ATPase activity and the interaction of the anesthetic with lipid and protein moieties by means of EPR and fluorescence spectroscopic techniques. Our results clearly show that below 5 mumol per mg protein, halothane interacts mainly with the lipid components of the membrane. This interaction is shown to be localized in the central core of the phospholipid bilayer and to induce an increase of the membrane calcium permeability. The interaction with protein components only occurs at higher halothane concentrations and affects its conformational and functional states. These results are discussed with respect to new insights into diethylether-SR membrane interaction and to malignant hyperthermia syndrome in the pig.

Animals↗
PubMed1990

Blood pressure and retinopathy in type I diabetes.

The relationship between blood pressure and diabetic retinopathy was evaluated in 249 young subjects with type I diabetes. Although hypertension is known to be associated with an increased risk for retinopathy, the effects of high-normal blood pressure are unknown. Retinopathy (158 of 249 subjects, 63%) is considerably more common in a young diabetic population than is hypertension (7 of 249 subjects, 2%). Thus, if blood pressure is important in the etiology or progression of diabetic retinopathy, levels below the hypertensive range (less than 141/90 mmHg) must be considered. The combined effect of hypertension and high-normal blood pressure (greater than 90th percentile but less than 141/90 mmHg) was studied. Elevation in diastolic blood pressure, alone, and in combination with elevated systolic blood pressure, correlated significantly (P less than 0.03) with retinopathy. The presence of high-normal blood pressure resulted in a prospectively higher occurrence of retinopathy and of progression of preexisting retinopathy. Glycohemoglobin (HbA1) and duration of diabetes also correlated with retinopathy. Both good glycemic control and maintenance of diastolic blood pressure below the 90th percentile for age may be important in relation to diabetic retinopathy.

Adolescent↗
PubMed1989

Plant cells contain calsequestrin.

Calsequestrin is a high capacity low affinity Ca2+-binding protein thought to be essential for the function of the intracellular rapid releasable Ca2+ pool of a variety of animal cells. Here we show that two types of plant tissues, cultured Streptanthus tortuosus cells and spinach leaves, contain a form of calsequestrin. In subcellular fractions of S. tortuosus cells, Stains-all staining reveals a metachromatically blue-staining 56,000-Da protein enriched in the microsomal fraction. This protein shares several biochemical characteristics with animal calsequestrin: 1) it changes its apparent molecular weight with the pH; 2) it is able to bind 45Ca2+ on nitrocellulose transfers; and 3) it is recognized by antibodies against canine cardiac calsequestrin. Calsequestrin was also identified in spinach leaves using a direct extraction procedure that was developed for muscle calsequestrin. Thus, our results demonstrate that plant cells contain calsequestrin within a subcellular membrane fraction. These results also suggest that calsequestrin is an ubiquitous protein rather than being limited only to animal cells.

Animals↗
PubMed1989

A common anti-DNA antibody idiotype and anti-phospholipid antibodies in sera from patients with schistosomiasis and filariasis with and without nephritis.

The serum concentration of a public idiotype (16/6 ID), originally identified on a human hybridoma-derived monoclonal anti-DNA antibody, was raised in patients with S. mansoni and filariasis with or without nephritis, compared to patients with S. haematobium (in which nephritis does not occur) or idiopathic nephritis not associated with infection. There was no significant difference in 16/6 ID levels between patients with or without renal disease, whether associated with S. mansoni or filarial infection. The 16/6 ID-positive antibodies did not bind to native or denatured DNA, using competitive fluid-phase inhibition studies. Anti-cardiolipin antibody (ACA) concentration was increased in patients with either S. mansoni or filarial infection. In filariasis, both IgG and IgM ACA isotypes were elevated, irrespective of the presence of nephritis. In S. mansoni infection, IgA ACA were limited to patients with renal disease, and IgG ACA isotype to patients without overt nephritis. Both isotypes of anti-cardiolipin antibody correlated with levels of the 16/6 ID in patients with S. mansoni or filariasis. The 16/6 idiotype was therefore a feature of chronic helminthic infection, but was not related to anti-DNA antibody levels or specificity. The occurrence of nephritis as a complication of these infections was not related to the prevalence of the 16/6 idiotype.

Antibodies, Antinuclear↗
PubMed1989

Afferent arteriolar C3 disease--a distinct pathological entity.

Afferent arteriolar C3 deposition was the sole histological abnormality in 79 and the major histological abnormality in an additional 39 of 959 renal biopsies performed over a 10-year period. Of these 79 patients, hematuria was the presenting symptom in 90%, with coincident loin pain in 49%. Urine microscopy of asymptomatic first-degree relatives revealed hematuria in 44% of children and siblings and 54% of parents, suggesting autosomal dominant inheritance. Arteriolar C3 deposition was confirmed by biopsy in four asymptomatic relatives with hematuria. Generalized thinning of glomerular basement membrane (less than 200 nm) was observed in five patients and focal thinning was observed in six patients with coincident afferent arteriolar C3 deposition. Seven other patients were identified as having generalized thinning of glomerular basement membrane in the absence of afferent arteriolar C3 deposition. Renal function was stable and similar in all groups studied over 37.9 +/- 23.7 months. No difference in clinical presentation or urinary abnormalities was evident between the groups. No arteriolar C3 deposition was evident in eight autopsy specimens with no known renal disease. It was concluded that afferent arteriolar C3 deposition is a marker of a distinct hereditary pathological entity, with differentiation from thin basement membrane disease not possible on clinical grounds. The medium- and long-term prognoses with respect to renal function are excellent.

Adolescent↗
PubMed1989

A nerve terminal protein with a selective distribution in spinal cord and brain.

A monoclonal antibody, designated S-7B8, recognizes a protein antigen localized to highly selected populations of nerve terminals in spinal cord and brain. The antibody produces dense immunocytochemical staining of primary afferent endings that synapse in superficial laminae of the spinal cord dorsal horn. Electron microscopy shows staining to be localized in nerve terminals where reaction product is associated primarily with spherical vesicles. In brain, S-7B8 immunoreactivity occurs in nerve terminals in sensory relay nuclei, most thalamic nuclei, and other selected areas, including the cerebellar molecular layer, the substantia nigra, the globus pallidus, and certain synaptic layers of the hippocampus and dentate gyrus. Endocrine glands and other tissues do not exhibit S-7B8 immunoreactivity. Although the antibody localizes to certain populations of nerve terminals that may use excitatory amino acid neurotransmitters, the distribution of S-7B8 immunoreactivity in the CNS does not correspond to that of any previously identified nerve terminal protein. Experiments to characterize the S-7B8 antigen indicate it may be an integral membrane component since extraction of synaptosomes with alkaline pH or high ionic strength does not release the antigen from the membranes. To identify the molecular weight of the S-7B8 antigen, synaptosomal membranes were solubilized in CHAPS and sequentially chromatographed on hydroxylapatite and then on DEAE anion-exchange resin to produce enriched fractions. When enriched fractions were separated on SDS-PAGE and Western blotted, the S-7B8 antibody specifically stained a protein migrating at 75,000 Da. This protein has been designated NT75. Preliminary studies of developing pathways show that the appearance of S-7B8 immunoreactivity in growing nerve endings corresponds closely to the time when synaptic connections are formed. Thus, the NT75 protein recognized by the S-7B8 antibody may have a role in the development and maintenance of specific synaptic endings.

Animals↗
PubMed1988

Evidence by NMR for mobility of the cytochrome domain within flavocytochrome b2.

According to a model proposed by Gervais, M, Groudinsky, O., Risler, Y. and Labeyrie, F. ((1977) Biochem. Biophys. Res. Commun. 77, 1543-1551) flavocytochrome b2 is composed of a central flavodehydrogenase entity of 4 X 45 kDa to which are attached four cytochrome b2 globules of approx. 11 kDa that are released after proteolysis of the connective loops. A possible inherent mobility of the latter with functional significance was suspected. Proton NMR spectra at 400 MHz of the isolated and of the flavodehydrogenase-bound ferricytochrome b2 units have been compared. In the ranges downfield of +12 ppm and upfield from -4 ppm, where hyperfine-shifted heme proton resonances reside, the chemical shifts are identical for the two forms, but the linewidths are markedly broader for flavocytochrome b2. The linewidths of three heme resonances, a methyl at +19 ppm, two single protons at -6 and -8 ppm (most probably from one vinyl) and an unassigned line at -2.4 ppm, all increase by a factor of about 4. Since, in the present case, linewidths are controlled mainly by proton/proton dipolar relaxations which are caused by molecular tumbling, a change in linewidths of about 15 would be expected if the cytochrome b2 globule had no free motion relative to the flavodehydrogenase domain. The present results thus support the previous hypothesis that such a relative mobility, of unknown correlation time and amplitude, actually exists.

Cytochrome b Group↗
PubMed1988

Lack of evidence of prolonged human immunodeficiency virus infection before antibody seroconversion.

Recently, considerable concern has been raised regarding the possibility that antibody-based screening tests for the human immunodeficiency virus (HIV) may fail to detect certain high-risk individuals for prolonged periods of time. It has been proposed that testing for HIV-related antigen may be a necessary procedure to detect such individuals. To address this issue, we longitudinally studied two groups of homosexual men: direct sexual partners of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) patients and individuals who ultimately sero-converted. There was no evidence of prolonged infection with HIV in the absence of detectable antibody in these two groups. It appears at this time that, even among subjects at very high risk for HIV infection, currently available antibody-based assays are sufficient to identify infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Amino-acid sequence of the cytochrome-b5-like heme-binding domain from Hansenula anomala flavocytochrome b2.

Flavocytochrome b2 (L-lactate dehydrogenase) from baker's yeast is composed of two structural and functional domains. Its first 100 residues constitute the heme-binding core, which is homologous to cytochrome b5 [B. Guiard, O. Groudinsky & F. Lederer (1974) Proc. Natl Acad. Sci. USA 71, 2539-2543]. We report here the amino acid sequence of the heme-binding domain isolated by tryptic proteolysis of Hansenula anomala flavocytochrome b2. The sequence was established by automated degradation of the whole fragment and of peptides obtained by CNBr cleavage at the unique tryptophan and by proteolysis with thermolysin and endoproteinase Lys C. As isolated, the domain consists of 84 residues without any sulfur amino acids. It shows 49 identities with the heme-binding domain from Saccharomyces cerevisiae and 28 with beef microsomal cytochrome b5. Using the recently published three-dimensional structure of S. cerevisiae flavocytochrome b2 [Z-x. Xia, N. Shamala, P. H. Bethge, L. W. Lim, H. D. Bellamy, N. H. Xuong, F. Lederer and F. S. Mathews (1987) Proc. Natl Acad. Sci. USA 84, 2629-2633], it can be seen that there are only positively charged side chains close to the accessible heme edge, the only negative charges in that area being those of the heme propionates. The implications of this result are discussed in the light of Salemme's model for the cytochrome b5/cytochrome c complex [F. R. Salemme (1976) J. Mol. Biol. 102, 563-568].

Amino Acid Sequence↗
PubMed1987

1H-NMR investigation of yeast cytochrome c. Interaction with the corresponding specific reductase (L-lactate cytochrome).

1H-NMR spectroscopy has been used to study the modifications of certain characteristic resonances of the Hansenula anomala yeast cytochrome c on binding to its specific reductase (flavocytochrome b2) or to the isolated cytochrome domain obtained from the entire molecule. Normal titration curves are observed for the resonances at 37.8 ppm assigned to heme c methyl 8 and at 19.4 ppm, line of cytochrome b2 spectrum. In contrast, the shifts near 3.2 and 3.4 ppm for trimethyl-lysine resonances of this cytochrome c present abnormal titration curves, saturation being apparently reached at low molar (cytochrome b2)/(cytochrome c) ratio. An interpretation is proposed in terms of shifts due to local conformational transitions induced by reductase binding but not rapidly reversible upon dissociation.

Cytochrome c Group↗
PubMed1987

Physical state abnormality of erythrocyte membrane in myotonic dystrophy: a spin label study.

Biophysical abnormalities of the erythrocyte membrane in muscular dystrophies have been described by numerous authors. This work presents the results we have obtained on 23 subjects suffering from myotonic muscular dystrophy (MyD, Steinert disease) by the spin label method. Two types of fatty acid spin labels were used: 5-nitroxide stearic acid (5NS) and 16-nitroxide stearic acid (16NS) which probe the membranes respectively near their polar heads and in their hydrophobic core. We measured the classical order parameter, the saturation behaviour of the electron paramagnetic resonance signal, and the label apparent rotation correlation time as a function of the temperature, on fresh and in vitro stored red blood cells. With the 5NS label, no differences were found between controls and patients. With the 16NS label, a highly significant variation in the thermic behaviour of the membrane is observed in its hydrophobic and fluid core. This last result may suggest some similarities between the red blood cell membranes of adult MyD's and healthy children.

Adolescent↗