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Biomedical subjects

M Roth

Publications and source records attributed to M Roth.

At least 289 records · Page 16Linked to original sources
PubMed1988

The 2-stage neuroskeletal pathomechanism of developmental deformities of the limb skeleton. A contribution to the discussion on the McCredie-McBride hypothesis.

Experimental skeletal deformities produced in laboratory birds and in frog tadpoles and examined with Williams' technique (1943) suggest a selective inhibitory effect of various teratogens upon the vulnerable growth of peripheral nervous trunks. The exaggerated osteoneural growth differential resulting therefrom is compensated for by adaptive deformities (buckling, achondroplasic stunting, dislocation) of otherwise normally growing bones which, though independent of innervation under normal conditions, have to "respect" the growth insufficiency of the nervous trunks and to accommodate along them during the proximo-distal development of the limb, even at the cost of a gross deformity. The McCredie-McBride hypothesis, on the other hand, is aimed at explanation of skeletal defects by an early neuroskeletal (neurotrophic) disturbance within the limb bud. Aneurogenic limbs produced experimentally do not necessarily militate against the existence of neuroskeletal relations in the early limb bud postulated, above all, by the McCredie-McBride hypothesis. These relations have been firmly established during the phylogenetic history so that artificial aneurogenic limb, never evolved by Nature, may grow up by (phylo)genetic inertia even without any neural involvement during the individual ontogenesis.

Animals↗
PubMed1987

Structure of RNA in satellite tobacco necrosis virus. A low resolution neutron diffraction study using 1H2O/2H2O solvent contrast variation.

The crystal structure of satellite tobacco necrosis virus has been studied by neutron diffraction at 16 A resolution using the technique of 1H2O/2H2O solvent contrast variation to distinguish between the regions of protein and nucleic acid. The RNA density is essentially localized in a region just inside the protein coat, leading to a significant interaction between the two components. From the appearance of the RNA density we conclude that the protein coat imposes partial icosahedral symmetry on a significant proportion of the nucleic acid. The shape and dimensions of the major part of this density suggests that about 72% of the total RNA could be double-helical in structure. The most important interaction between the two components of the virus occurs between the N-terminal triple-helical arms of the protein subunits and those regions of the RNA density that could have a double-helical secondary structure.

Amino Acid Sequence↗
PubMed1987

Age and histopathologic heterogeneity in Alzheimer's disease. Evidence for subtypes.

In support of heterogeneity in Alzheimer's disease (AD), the existence of clinical and biologic subtypes has been claimed. We have investigated this claim by a statistical analysis of the relationships between the number of neurons in nucleus locus ceruleus (nLC), cortical levels of neurotransmitters, number of cortical plaques and tangles, and age. We separated AD patients into two groups: AD-1, with a less severe loss of nLC neurons; and AD-2, with a greater loss. The AD-2 cases were associated with less choline acetyltransferase activity, smaller concentrations of somatostatin and norepinephrine, and more plaques and tangles in the cerebral cortex. Although the mean age at death was less and the duration of dementia was greater in AD-2 patients than in AD-1 patients, the differences in these age-related variables were not significant. Further evidence of heterogeneity came from discriminant function analyses based on nLC neuronal counts and age at death. These findings, suggesting two subtypes of AD, suggest heterogeneity.

Age Factors↗
PubMed1987

Yeast tRNA(Asp)-aspartyl-tRNA synthetase complex: low resolution crystal structure.

Yeast aspartyl-tRNA synthetase, a dimer of molecular weight 125,000, and two molecules of its cognate tRNA (Mr = 24160) cocrystallize in the cubic space group I432 (a = 354 A). The crystal structure was solved to low resolution using neutron and X-ray diffraction data. Neutron single crystal diffraction data were collected in five solvents differing by their D2O content in order to use the contrast variation method to distinguish between the protein and tRNA. The synthetase was first located at 40 A resolution using the 65% D2O neutron data (tRNA matched) tRNA molecules were found at 20 A resolution using both neutron and X-ray data. The resulting model was refined against 10 A resolution X-ray data, using density modification and least-squares refinement of the tRNA positions. The crystal structure solved without a priori phase knowledge, was confirmed later by isomorphous replacement. The molecular model of the complex is in good agreement with results obtained in solution by probing the protected part of the tRNA by chemical reagents.

Amino Acyl-tRNA Synthetases↗
PubMed1987

Immunochemical determination of an initial step in thymine dimer excision repair in xeroderma pigmentosum variant fibroblasts and biopsy material from the normal population and patients with basal cell carcinoma and melanoma.

A monoclonal antibody specific for u.v.-induced thymine-thymine dimers in single-stranded DNA has been used in an enzyme immunoassay to investigate the loss of antigenicity associated with repair of this lesion in the first 2 h following 10 J/m2 254 nm radiation. Variances of +/- 10% for the method and +/- 6.5% for individuals were established using primary cultures of biopsies from healthy individuals. No differences in the rate of loss of antigenicity was observed between 20 normal lymphocyte samples and 10 normal skin biopsies. Of three xeroderma pigmentosum (XP) variant cell lines tested, GM3617 could not be distinguished from normal cells but GM1227 and GM3053 showed lower rates of loss than any of the healthy samples. When the group mean values were compared there was no significant difference between normals and biopsies from sun-shielded skin areas from 16 basal cell carcinomas but similar material from 10 melanoma patients showed a significantly reduced (P = 0.001) rate of loss of antigenicity. Since the rate of loss of antigenicity in normal and XP variant cells reflected their relative abilities to perform unscheduled DNA synthesis, our results suggest that some melanoma patients may also have a minor deficiency in an early stage of excision repair.

Adult↗
PubMed1987

Neuronal degeneration in locus ceruleus and cortical correlates of Alzheimer disease.

Relationships were examined between neuronal degeneration in the nucleus locus ceruleus (nLC), a parameter of central noradrenergic impairment, and neocortical markers of Alzheimer disease (AD). The loss of nLC neurons was found to correlate significantly with norepinephrine concentration, choline acetyltransferase (ChAT) activity, and numbers of plaques and tangles on Brodmann area 24 (cingulate); ChAT and plaque counts in area 21 (temporal); and with ChAT activity in area 10 (frontal). In addition, nLC neuronal counts were correlated significantly with the severity and estimated duration of dementia. The number of neurofibrillary tangles in nLC, which did not correlate significantly with neocortical markers of AD, correlated with the estimated duration and severity of dementia. These data suggest that changes in central noradrenergic pathways are related to the pathophysiology of AD.

Aged↗
PubMed1987

Quantitative analysis of the binding and oligomerization of staphylococcal alpha-toxin in target erythrocyte membranes.

The binding of staphylococcal alpha-toxin to rabbit and human erythrocytes was quantitated over a wide range of toxin concentrations (3 x 10(-11) to 3 x 10(-6) M) with the use of an enzyme-linked immunosorbent assay that permitted simultaneous quantitation of monomeric and oligomeric toxin forms. Three basic observations were made. First, in no range of concentrations did the binding of alpha-toxin to rabbit erythrocytes display characteristics of a receptor-ligand interaction. Net binding to rabbit cells was nil at sublytic concentrations (10(-10) M or 3 ng/ml). The onset of binding occurred at around 10 ng/ml and remained fairly constant and ineffective (5 to 8% of toxin offered) over a wide concentration range (up to 10 micrograms/ml). Second, hemolysis of rabbit and human erythrocytes at 37 degrees C was always accompanied by the formation of toxin oligomers in the membrane. Third, overall toxin binding at 0 degree C followed a pattern similar to that at 37 degrees C. However, oligomer formation and cell lysis were retarded (but not totally inhibited) at 0 degree C. When rabbit erythrocytes were incubated with low levels of toxin at 0 degree C (0.5 microgram/ml) for 30 min, the toxin became bound exclusively in monomer form, and no lysis occurred. When cells thus treated were washed and suspended at 37 degrees C, lysis rapidly ensued, and native monomeric toxin was replaced by oligomeric toxin. The collective results directly support the oligomer pore concept of toxin action and also indicate that toxin oligomers form by lateral aggregation of bound monomers in the bilayer. They speak against the existence of specific binding sites for alpha-toxin on rabbit erythrocytes.

Animals↗
PubMed1987

The dexamethasone suppression test and prediction of outcome in patients receiving ECT.

Twenty-six in-patients satisfying DSM-III criteria for major depressive episode were assessed using the Newcastle Diagnostic and ECT Predictor Scales and the dexamethasone suppression test (DST), prior to commencing a course of electroconvulsive therapy (ECT). The Newcastle ECT Predictor Scale was successful in predicting both immediate outcome and outcome over the 6 months following ECT; the DST was unsuccessful in predicting either immediate or 6-month outcome.

Adult↗
PubMed1986

Decreased somatostatin immunoreactivity but not neuropeptide Y immunoreactivity in cerebral cortex in senile dementia of Alzheimer type.

The content of two neuropeptides, somatostatin (SRIF) and neuropeptide Y (NPY) has been determined in two cerebral cortical areas of Alzheimer's disease brain and in age-matched control brains. The content of SRIF-like immunoreactivity (SRIF-LI) was found to be decreased in Alzheimer temporal cortex (Brodmann area 21) compared to control temporal cortex. The decreased content of SRIF was significantly correlated with the observed number of neuritic plaques and neurofibrillary tangles. No difference was observed in NPY-LI between Alzheimer cerebral cortex and control cortex. Furthermore, no correlations were observed between NPY content and plaque count, neurofibrillary tangle estimate or SRIF content despite widespread reports of NPY/SRIF coexistence.

Aged↗
PubMed1986

Cranio-cervical growth collision: another explanation of the Arnold-Chiari malformation and of basilar impression.

Analysis of neuro-cranio-spinal development suggests a cranio-cervical growth conflict as the cause of the Arnold-Chiari malformation and of basilar impression. The ascending course and elongation of the upper cervical nerves associated with the Arnold-Chiari malformation reflects the abnormal, caudo-cranially proceeding growth of the cervical spine. This is the opposite of the normal cranio-caudal direction of growth (which includes the brain) with downward slanting of the cervical nerve roots. The cervical growth reversal is a compensatory event related to the impairment of distal spinal growth at the level of the coexistent myelomeningocele. With the reversal of the cerical growth, the initial descent (uncoiling) of the primordial brain curvatures is compromised owing to the growth-collision with the ascending cervical spine. Their subsequent growth proceeds into the upper cervical spinal canal. The contents of the posterior cranial fossa are actively "sucked up", "devoured" by the latter. In contrast to the adaptively enhanced growth of the early cranio-cervical nervous structures in the Arnold-Chiari malformation, as an answer to the growth-shifts of the encasing skeleton, basilar impression is a postembryonic adaptation of the cervico-cranial skeleton to the inadequate growth of the nervous structures after the latter have lost their growth adaptability. Arnold-Chiari malformation and basilar impression are just two representatives of "osteo-neural growth pathology" encompassing some "dysplastic" disorders of the axial as well as of the limb skeleton such as platyspondyly, scoliosis, Scheuermann's kyphosis, achondroplasia-like conditions, congenital dysplasia of the hip etc.(ABSTRACT TRUNCATED AT 250 WORDS)

Arnold-Chiari Malformation↗
PubMed1986

Production of listeriolysin by beta-hemolytic strains of Listeria monocytogenes.

Listeriolysin was isolated from target rabbit erythrocyte membranes after lysis of the cells with partially purified toxin derived from a culture supernatant of Listeria ivanovii. The membrane form of the toxin exhibited properties similar to those previously found for streptolysin O. Detergent-solubilized, delipidated listeriolysin was found to comprise a heterogeneous population of partially and fully circularized, amphiphilic oligomers whose embedment within the lipid bilayer generated large transmembrane pores. The molecular weight of the toxin monomer was estimated to be 55,000 to 60,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunological cross-reactions between the toxin and streptolysin O were demonstrable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. An immunoblot assay for detecting listeriolysin in agar-incorporated, lysed erythrocyte membranes was developed, and 28 defined, clinical isolates of Listeria monocytogenes were examined for toxin production. These isolates caused beta-hemolysis on the agar plates and had previously been regarded as listeriolysin producers. However, we found that only two isolates produced genuine listeriolysin, since the sensitive immunoblot assay entirely failed to detect the toxin in all other cases. We excluded that this finding derived from proteolytic degradation of membrane-bound toxin. Thus, the great majority of human pathogenic Listeria strains appear to produce one or several hemolysins that are immunologically and, by inference, molecularly distinct from the streptolysin O-related listeriolysin. We propose that the streptolysin O-related toxin be designated alpha-listeriolysin and that the other hemolysin(s) be termed beta-listeriolysin.

Animals↗