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Biomedical subjects

M Roth

Publications and source records attributed to M Roth.

At least 325 records · Page 18Linked to original sources
PubMed1984

A simple method for quantitative measurement of C3d in human plasma.

We describe a simple and reliable method for quantitating C3d in human plasma. The method rests on the finding that native C3 and its activation/inactivation product C3c bind to Concanavalin A, whereas C3d does not. Rocket affinoimmunoelectrophoresis with Con-A Sepharose incorporated into an intermediate gel permits quantitation of free C3d in 2-20 microliters aliquots of EDTA-plasma without any manipulation prior to sample application. Using this method, we found that the level of circulating C3d in plasma of 30 healthy donors was usually well below 3% of maximally convertable C3d.

Complement C3↗
PubMed1984

Crystal structure of the nucleosome core particle at 16 A resolution.

The crystal structure of the nucleosome core particle has been studied by neutron diffraction to a resolution of 16 A. By using H2O/D2O solvent contrast variation, the structures of the DNA and histone core were analysed separately. The DNA, as seen at this resolution, forms a super-helix of pitch 25.8 A, radius 42.1 A and 1.8 turns in length. The histone core itself is approximately helical and follows the DNA along the inside of the super-helix, giving the nucleosome core particle an overall 2-fold axis of symmetry. Four regions can be distinguished in the protein density, which we interpret as dimers of histones within the octameric core. The dimers have been assigned on the basis of other evidence as being of two kinds, (H2A-H2B) and (H3-H4). Because solvent contrast variation can distinguish between hydrophobic and hydrophilic regions in the protein density, our results suggest that the interface between the monomers of each dimer is probably quite hydrophobic in character, while the interaction between dimers is weaker and/or more hydrophilic. The protein is in contact with most of the DNA and there are some regions where it may penetrate between the turns of the super-helix. In particular, the tetramer (H4-H3)-(H3-H4) is in close contact with the central part of the DNA, but significant contacts are seen also between the histones H3 and the extremities of the super-helix, thus explaining the stability of a nucleosome-like particle depleted of H2A and H2B. Significant departures from the molecular 2-fold axis of symmetry occur in the relative arrangements of the two (H2A-H2B) dimers.

Crystallography↗
PubMed1984

Neurochemical characteristics of early and late onset types of Alzheimer's disease.

Brains of 49 patients who had died with Alzheimer's disease and 54 controls were examined. The Alzheimer group exhibited noticeably reduced activity of the cholinergic marker enzyme choline acetyltransferase in the cerebral cortex, but cortical concentrations of noradrenaline, gamma-aminobutyric acid, and somatostatin were also significantly reduced. Analysis of the results according to age at death showed that the older patients, dying in their 9th and 10th decades, had a relatively pure cholinergic deficit confined to temporal lobe and hippocampus, together with a reduced concentration of somatostatin confined to temporal cortex. By contrast, the younger patients, dying in their 7th and 8th decades, had a widespread and severe cholinergic deficit together with the abnormalities of noradrenaline, gamma-aminobutyric acid, and somatostatin, and the younger patients accounted for most of the abnormalities in these systems observed in the overall group. Comparison of the young subjects with Alzheimer's disease with the older controls did not support the concept of Alzheimer's disease representing an acceleration of the aging process. These results suggest that Alzheimer's disease in people aged under 80 may represent a distinct form of presenile dementia which differs in important respects from the dementia of old age.

Age Factors↗
PubMed1984

Reduced binding of [3H]ketanserin to cortical 5-ht2 receptors in senile dementia of the Alzheimer type.

Using [3H]ketanserin, a specific ligand for the 5-HT2 receptor, the amount of specific binding was measured in preparations of post-mortem frontal cortex from subjects diagnosed as suffering from dementia. A highly significant 42% loss of binding was observed which reflected a decrease in receptor density compared to psychiatrically normal controls. This was found to be independent of age in the demented patients and thus unlikely to be related to the cholinergic deficit. Measurement of 5-HT and its metabolite 5-HIAA indicated a smaller, non-significant decrease in presynaptic 5-HT function.

Age Factors↗
PubMed1984

Correlation of cortical cholinergic and GABA deficits with quantitative neuropathological findings in senile dementia.

The present paper examines the relationship between choline acetyltransferase (ChAT) activity and gamma aminobutyric acid (GABA) concentrations with neuronal counts, senile plaque counts and estimates of neurofibrillary tangles in a series of 25 cases of senile dementia of Alzheimer type (SDAT) with appropriate controls. ChAT activity was significantly positively correlated with neuronal counts in the frontal and temporal region for the whole group but not in the demented or control subgroups. Significant negative correlations were also found between plaque counts and ChAT activity in all areas studied in the total group of subjects and in most of the SDAT groups. Significant negative correlations between ChAT activity and estimates of neurofibrillary change occurred in the frontal area and midtemporal gyrus in the SDAT cases. All the above correlations were seen most prominently in the youngest dementia patients (less than 79 years of age) who exhibited the most severe neuropathological and neurochemical deficits. The neurochemical distinction between the young and elderly age group of SDAT cases was well illustrated by the paradoxical trends of significantly increased GABA and ChAT levels with increasing age. The few significant correlations observed between GABA and cell counts were positive and occurred in the temporal lobe in the younger age group. Plaque counts and neurofibrillary tangle estimates showed little correlation with GABA concentrations.

Alzheimer Disease↗
PubMed1984

Isolation and identification of two hemolytic forms of streptolysin-O.

Streptolysin-O was isolated from culture supernatants of group-A beta-hemolytic streptococci (Richards strain) by ammonium sulfate and polyethylene glycol precipitation, DEAE-ion exchange chromatography, preparative isoelectric focusing, and chromatography on Sephacryl S-300. Two forms of the toxin possessing similar hemolytic capacity were identified. The native toxin was a single polypeptide chain devoid of amino sugars with a sedimentation coefficient of 3.9S and a molecular weight of 69,000, and was isoelectric at pH 6.0 to 6.4. Partial degradation of the native toxin occurred during the isolation procedure, yielding a hemolytically active polypeptide with a molecular weight of 57,000 and a pI of 7.0 to 7.5. Both forms of the toxin generated the typical, heterogeneous, open and closed ring-structured channels in erythrocyte membranes. Structural considerations indicated that between 25 and 100 monomer toxin molecules constituted the individual ultrastructurally recognizable channels. Hemolytic titrations indicated that the presence of 70 to 125 toxin molecules per erythrocyte was required to generate an average of one functional lesion per cell. The data are consistent with the concept that one or very few streptolysin-O channels will cause hemolysis.

Amino Acids↗
PubMed1984

Griseochelin, a novel carboxylic acid antibiotic from Streptomyces griseus.

Griseochelin, C33H60O7, isolated from an asporogenous strain of Streptomyces griseus represents a novel carboxylic acid antibiotic. The metabolite, which is active against Gram-positive bacteria, forms water-insoluble salts with mono- and divalent cations and binds alkaline-earth metal ions specifically in 2:1 (X2M) stoichiometry. Detailed spectral (IR, MS and NMR) studies provide full characterization of its constitution featuring a carboxylic acid function, a substituted tetrahydropyran ring, an allylic OH group which are accommodated within a tetrahydroxylated-octamethyl-C25 diene backbone.

Animals↗
PubMed1984

Agoraphobia, panic disorder and generalized anxiety disorder: some implications of recent advances.

The nature of the relationship between 'panic disorder', agoraphobia and general anxiety disorder remains open. The aetiological theories which have tried to link them with the aid of biological and psychological concepts fail to take account of conflicting observations. 'Panic' attacks are not confined to agoraphobic and related disorders, being indistinguishable from the attacks of acute anxiety and phobic aversion manifest in a wide range of anxiety and affective disorders. There is continuity and discontinuity in the evolution of agoraphobia; those affected differ in respect of a range of premorbid features from patients with other disorders and control subjects. These variables include family history, life development, trait anxiety and other personality characteristics including introversion, neuroticism and probably emotional dependence on others. Not all the claims made on behalf of the efficacy of pharmacological treatment on the one hand and behavioural therapies on the other are substantiated. The success achieved by behavioural treatment appear to endure over some years. But the residual disabilities and defects that follow all forms of treatment and the problems posed by patient selection and high drop-out rates have received insufficient attention. Aetiological theories of agoraphobia and related conditions have been advanced along biomedical, psychological and psychodynamic lines. Some evidence supports each kind of theory. But none is wholly consistent with the findings regarding its phenomenology and evolution. Recent biological investigations have led to the formulation of hypotheses in relation to anticipatory and chronic anxiety in terms of changes in synaptic connections, enhancement of transmitter release as well as alterations in molecular configuration and regulation of gene expression. It would be premature to conclude that these findings can provide a unitary conceptual framework for the explanation of human anxiety disorders. The psychological, behavioural and psychodynamic aspects of this group of disorders should all continue to receive due attention both in clinical management and scientific investigation.

Adolescent↗
PubMed1983

Determination of pancreatic carboxypeptidase A in human blood serum.

A method has been designed for the assay of pancreatic carboxypeptidase A in blood serum. It uses Z-Gly-Phe as the substrate and fluorimetric determination of the released phenylalanine in an amino acid analyser, which yields a measure of free carboxypeptidase A. In addition, the sum (free carboxypeptidase A + procarboxypeptidase A) can be determined on a second portion preincubated with trypsin, which converts the proenzyme to the active form. Determinations made in fifteen healthy individuals showed the presence of a measurable concentration of free carboxypeptidase A. In acute pancreatitis, total carboxypeptidase A is raised. An increase in circulating proenzyme is observed in some cases. Data from 46 patients show a good correlation between total carboxypeptidase A, lipase and immunoreactive trypsin. Differential determination of procarboxypeptidase A and free carboxypeptidase A provides an interesting new tool for the diagnosis of pancreatic disorders.

Acute Disease↗
PubMed1983

Loss of pigmented dopamine-beta-hydroxylase positive cells from locus coeruleus in senile dementia of Alzheimer's type.

Serial sections of human brainstem were used to determine the total number of pigmented cells in locus coeruleus and, by immunohistochemical staining using an antiserum directed against human dopamine-beta-hydroxylase (DBH), the number of DBH-positive cells. In 12 brains from elderly control and dementia subjects there wer not significant differences in the total cell populations determined in the same brain by the two techniques. In 6 patients with senile dementia of Alzheimer's type there was a variable loss (average about 60% reduction) in locus coeruleus cells when compared to controls of similar age. The loss of noradrenergic neurones from locus coeruleus was accompanied by an average reduction of similar magnitude in noradrenaline concentration in temporal cortex, with no change or an increase in dopamine content. There was also a significant reduction in the cholinergic marker choline acetyltransferase in cortex samples from the dementia cases.

Aged↗
PubMed1983

Cortical neuronal counts in normal elderly controls and demented patients.

The purposes of the investigation were to determine whether there was significant neuronal loss in dementia, and if so, whether it was general or localised, and to examine the relationship between neuronal counts, senile plaques and neurofibrillary change. Neuronal counts were made in nine cortical areas in the brains of 25 patients with senile dementia of the Alzheimer type and twenty-five age-matched controls, with the aid of an image analysing computer. Neuronal counts per square millimetre were significantly lower in the demented group of patients in the inferior frontal and superior temporal gyri. Neuronal counts in four columns of cortex were significantly reduced in superior, middle and inferior frontal gyri, cingulate gyrus and superior and middle temporal gyri. There was no significant difference in the parietal (Brodmann area 7) or occipital (Brodmann area 17) cortex. Corresponding glial counts per square millimetre show a significant increase in the demented group only in the middle and inferior temporal gyri. Neuronal counts correlated weakly but significantly with plaque counts in the same cortical area in the middle frontal gyrus and the superior and middle temporal gyri. High correlations between neuronal counts and estimates of neurofibrillary change were found in superior, middle and inferior frontal gyri, cingulate gyrus and superior and middle temporal gyri.

Aged↗
PubMed1983

Yeast tRNAAsp-aspartyl-tRNA synthetase: the crystalline complex.

Aspartyl-tRNA synthetase from yeast, a dimer of molecular weight 125,000 and its cognate tRNA (Mr = 24,160) were co-crystallized using ammonium sulfate as precipitant agent. The presence in the crystals of both components in the two-to-one stoichiometric ratio was demonstrated by electrophoresis, biological activity assays and crystallographic data. Crystals belong to the cubic space group I432 with cell parameter of 354 A and one complex particle per asymmetric unit. The solvent content of about 78% is favorable for a low resolution structural investigation. By exchanging H2O for D2O in mother liquors, advantage can be taken from contrast variation techniques with neutron radiations. Diffraction data to 20 A resolution were measured at five different contrasts, two of them being close to the theoretical matching point of RNA and protein in the presence of ammonium sulfate. The experimental extinction of the diffracted signal was observed to be close to 36% D2O, significantly different from the predicted value of 41%. The phenomenon can be explained by the existence of a large interface region between the two tRNAs and the enzyme. These parts of the molecules are hidden from the solvent and their protons are less easily exchangeable. Accessibility studies toward chemicals of tRNAAsp in solution and in the presence of synthetase are in agreement with such a model.

Amino Acyl-tRNA Synthetases↗