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Biomedical subjects

M Roth

Publications and source records attributed to M Roth.

At least 73 records · Page 4Linked to original sources
PubMed1989

The phenomenological study of 90 patients with panic disorder, Part II.

This paper examines the nosological and aetiological relationships of panic disorder to the anxiety states and depression. The phenomenology is detailed from an unbiased sample of 90 cases selected, on the basis of meeting positive criteria for panic disorder, from 3 series of consecutive cases. Panic attacks were found to be only quantitatively distinct from non-panic anxiety. Truly spontaneous attacks, not preceded by anxiety-provoking cognitions, were uncommon. No unique association with agoraphobia was seen, other anxiety states and depression being common. Social phobia and generalized anxiety often preceded the development of panic disorder, as did some cases of agoraphobia. Depression was usually non-specific and secondary when only DSM-III MDE criteria were used. Significant neurotic traits were found, particularly anxiety, dependency and poor sexual adjustment. Panic disorder has multiple causal factors only one of which is a genetic tendency for panic attacks. While important therapeutically, panic attacks should not be given the primary place in diagnosis.

Adult↗
PubMed1989

[The "envelope" versus the biomechanical function of the spine].

As a continuation of argumentation presented in a number of previous communications, the author advocates the view according to which the developing spine and its neural content ["spinal cord-nerve roots complex"] are linked by an equally intimate morphogenetic relation like that existing between the brain and its skeletogenic envelope. A specific feature of the neurovertebral developmental relation consists in the fact that the elongated spinal cord-nerve roots complex is enveloped by its skeletogenic case both in the transversal and in the longitudinal direction. The matter is further complicated by lagging of the spinal neural growth behind that of the vertebral column. The development of the basic anatomical features of the individual vertebrae such as their length and width, the girth of the vertebral body as well as the shape of the intervertebral foramina cannot be understood without taking into account the gross developmental dynamics of the two main components of the axial organ, viz., of the spinal cord-nerve roots complex and of the vertebral column.

Animals↗
PubMed1988

Do general practitioners miss dementia in elderly patients?

General practitioners and community nurses were asked to rate the likelihood of dementia for each of their elderly patients. Cases of dementia were identified by research psychiatrists using the Cambridge mental disorders of the elderly examination (CAMDEX), a new structured diagnostic interview. General practitioners correctly identified dementia as at least a possibility in 121 of the 208 cases found. Nevertheless, they mistakenly rated as demented several patients suffering from functional psychiatric disorders, in particular depression. Community nurses correctly identified dementia as at least a possibility in 64 of the 74 demented patients known to them, but they incorrectly suspected dementia in a greater proportion of instances. Both general practitioners and families appeared to have low expectations of what general practice has to offer demented elderly people. General practitioners should take the initiative in diagnosing dementia in very elderly patients who show signs of the condition. In some cases it may be secondary to treatable disorders, and in others all that may be required are understanding, support, and advice to families.

Aged↗
PubMed1988

A single amino acid change in the cytoplasmic domain allows the influenza virus hemagglutinin to be endocytosed through coated pits.

Through site-specific mutagenesis, three of the ten amino acids of the cytoplasmic domain of the influenza virus hemagglutinin (HA) were individually changed to tyrosines. None of these changes had significant effect on the rate of export, the rate of folding, or the antigenicity of the mutant HAs. However, one of these mutations, substituting tyrosine for cysteine at amino acid 543, changed HA from a protein that was endocytosed at a very low rate to a protein that readily entered coated pits, was internalized, and apparently recycled to the cell surface. Replacement of cysteine 543 with phenylalanine or serine did not increase the rate of internalization of HA. Phosphorylation of the mutant HA bearing a tyrosine at position 543 was not detected. These results indicate a specific and local role for the tyrosine introduced into the cytoplasmic domain of HA that is necessary for interaction of the protein with coated pits.

Amino Acid Sequence↗
PubMed1988

Molecular titration as a means of calibrating enzyme reference materials.

Active site titration provides a means of calibrating enzyme reference materials in molecular concentration units independent from the incubation conditions used in kinetic assays. Such reference materials may serve as primary standards for calibrating any kinetic assay using the same active site. Active site titration of aspartate aminotransferase has been done by fluorimetric measurement of the half-cycle transamination of the phosphopyridoxal form. Another promising approach is the stoichiometric titration with specific suicide substrates such as vinylglycine. Expression of results in molecular concentration units requires that both the primary enzyme standard and the enzyme as measured in blood plasma show similar turnover numbers and substrate specificity in the kinetic assay being used. This is best achieved with purified reference materials of human origin. If the assay in plasma measures the sum of several isoenzymes having different turnover numbers, then the calibration is no longer absolute but becomes method-dependent.

Binding Sites↗
PubMed1988

Thymine dimer repair in fibroblasts of patients with dysplastic naevus syndrome (DNS).

Dysplastic naevus syndrome (DNS) is frequently observed in association with familial melanoma and xeroderma pigmentosum (XP), but the role of UV-light in the development of DNS has not been elucidated. Previous work has shown that UV-induced unscheduled DNA synthesis is associated with the early loss of antigenicity observed in immunoassays using a monoclonal antibody specific for thymine-thymine dimers. We now show that the rate of loss of antigenicity, which reflects the relative amount of bound antibody, observed during the first 60 min following 10 Jm-2 UVC irradiation is significantly reduced (p = 0.02) in cultures of fibroblasts from 7 out of 8 DNS patients compared with the results from cells of a group of 30 healthy volunteers. This observation suggests an early event in excision repair is altered in the majority of DNS patients.

Adult↗
PubMed1988

Quantitative whole-body autoradiographic analysis of the tissue distribution of orally-administered [14C]cholesterol in hypercholesterolemic rats.

The cholesterol-fed rat model has been used to examine the distribution of radiolabeled cholesterol by whole-body autoradiographic and quantitative videodensitometric methods. Animals were fed a hypercholesterolemic diet for 7 days, and were subsequently killed at 3, 6, 12, 24, or 72 h following a single oral dose of [14C]cholesterol. Maximum blood and tissue levels were observed at 12 h, while liver and adrenals were the most intensely labeled tissues. Liver maintained consistently high levels over the course of the study, while activity in other tissues declined moderately by 72 h, indicating the long half-life of cholesterol radioequivalents in tissue. The results of these experiments suggest that autoradiographic examination of cholesterol distribution in animals treated with pharmaceutical agents designed to modify cholesterol absorption or clearance will be useful in providing supplemental or confirmatory information on the drugs' mode of action.

Animals↗
PubMed1988

Anxiety, panic and phobic disorders: an overview.

This paper reviews anxiety, panic, and phobic disorders as they were described in landmark works, along with more recent epidemiologic studies of the disorders. The author discusses clinical syndromes of anxiety as outlined in the DSM-III: agoraphobia, social phobia, generalized anxiety disorder, panic disorder, simple phobic states, and obsessive-compulsive disorder, relating them to Phobic Anxiety-Depersonalization Syndrome and to earlier descriptions by Westphal and Benedict. The paper addresses the problem of delineating anxiety and phobic states from depressive disorders, with regard to diagnosis and treatment outcome. Various etiological bases of agoraphobia, panic, and anxiety disorders are suggested: heredity, life events and circumstances, family background and developmental history, the premorbid personality, and some psychological aspects. Several questions are explored on the relationships of agoraphobia, anxiety and panic attacks. For example, is agoraphobia a new disease or one stage in the development of severe chronic anxiety? Are the phobias of agoraphobia acquired by conditioning or learning? Are "panics" spontaneous or physiological? Are panic attacks the first event in the primary cause of agoraphobia? For future work the authors propose a reassessment of the prevalence of agoraphobia and related disorders, a more careful definition of the agoraphobic disorders, and thorough clinical investigation of the various treatment modalities in well-defined populations. The past twenty years' achievements in behavioural and pharmacological treatments for agoraphobia are briefly recapitulated.

Agoraphobia↗
PubMed1988

Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease.

A substantially enriched preparation of Alzheimer paired helical filaments (PHFs) has been used as a starting point for biochemical studies. Pronase treatment, which strips off adhering proteins, leaves a resistant core that is structurally intact. This has been used to raise a monoclonal antibody that decorates the filament core. The antibody has been used to follow the extraction of two peptide fragments (9.5 and 12 kDa) by immunoblotting. The link between the PHF as a morphological entity and these peptides has been established independently by photoaffinity labeling with a chemical ligand to the PHF core. Sequence analysis of these peptides was used to design oligonucleotide probes for cloning a cognate cDNA, which leads to its identification as human microtubule-associated tau protein. The sequencing of the 9.5- and 12-kDa peptides shows they are derived from a conserved region of tau containing three repeating segments. Since these fragments have been copurified with the Pronase-resistant core and are only released by subsequent steps, the corresponding part of the tau molecule must be tightly bound in the PHF core.

Alzheimer Disease↗
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↗