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Biomedical subjects

R Levy

Publications and source records attributed to R Levy.

At least 613 records · Page 34Linked to original sources

The retention of new information in senile dementia.

Paired associate learning performance of demented patients was assessed repeatedly over six months. Patterns of change of performance for repeated and for changing items were compared. Performance on changing items progressively declined, performance on repeated items was maintained at initial levels. This difference was significant and indicates that these patients are able to retain same information over one- and two-month intervals.

Alzheimer Disease↗

Computed tomography in the elderly: changes over time in a normal population.

The clinical, psychometric, and computed tomographic (CT) status of previously fit elderly volunteers is described at follow-up for up to four years. A number of relationships were found between psychometric and CT scores, but a dementing group could not be determined on the basis of a single scan. However, a subtle reduction in cognition over time was significantly related to CT changes, and occurred in 10%. Larger ventricles were also found in a small sub-group, who developed late-onset depressive disorders; recent bereavement was related to ventricular size. Thus a single CT scan may not be a useful discriminatory test in early dementia, but a repeat demonstrating ventricular enlargement, is likely to be significant. In the elderly, cognitive and CT scan deterioration should not be expected unless a disease process is occurring; this may be indicated by subtle cognitive impairment or by late-onset depressive disorder.

Aged↗

Computed tomographic density numbers. A comparative study of patients with senile dementia and normal elderly controls.

Cranial computed tomography (CT) scans of 48 patients with senile dementia of the Alzheimer type (SDAT) and 40 normal elderly volunteers were compared. The demented group were found to have significantly larger lateral ventricles assessed planimetrically and by using a linear measure of the ratio of the maximum width of the frontal horns of the lateral ventricles to the maximum intracranial diameter. Attenuation density was computed for 15 brain regions. The demented group did not differ significantly from the normal controls with respect to attenuation density in any of the regions studied.

Aged↗

Hypothesis: the gingival tissue as a reservoir for herpes simplex virus.

The reservoir site of Herpes simplex virus (HSV), from the primary infection until reactivation and in between recurrences was found to be in the dorsal roots of the trigeminal ganglion or in the sensory root ganglion. However, the triggering of viral genome in the ganglion does not exclusively explain the recurrences and appearance of skin lesions. Other sites cannot, therefore, be excluded, and virus may well be occult also in extraneural tissues. Herpes virus antigens were found by us in the sulcular epithelium of approximately 60% of patients with clinically healthy gingivae; we therefore hypothesised that the epithelial cells might act as the preferential site for latent HSV. In order to prove this assumption, viral genome should be traced in cells of oral tissues, and efforts should be made to rescue virus.

Antibodies, Viral↗

Focal cerebral ischemia in the cat: effect of naloxone on cortical blood flow and neurological deficit following middle cerebral artery occlusion.

The effect of the opiate antagonist naloxone on both the neurological deficit and regional cortical blood flow after middle cerebral artery occlusion in the cat was investigated. In animals with mild symptoms, naloxone did not consistently produce a significant behavioral effect. In all cats with neurological deficits, including hemiplegia or severe hemiparesis, 2 mg/kg naloxone administered intravenously 4 h after the ischemic lesion produced a reversal of neurological symptoms. This effect began within 2 min following naloxone injection and lasted for approximately 20 min. Animals were then anesthetized and cortical blood flow was measured by the hydrogen clearance method. Average cortical blood flow on the side of the occlusion was 50% that of the control side. Naloxone produced a significant additional decrease of 19.5% in cortical blood flow in the ischemic hemisphere, whereas no effect on blood flow on the control side was noted. Thus, although naloxone appears to temporarily reverse the severe neurological deficits resulting from middle cerebral artery occlusion in the cat, this effect appears to be accompanied by a decrease in local blood flow to the ischemic cortex.

Animals↗

Detection of B-cell lymphoma in peripheral blood by DNA hybridisation.

As an alternative to morphological identification of circulating neoplastic lymphocytes in the blood of patients with non-Hodgkin's lymphoma, DNA of peripheral blood lymphocytes was analysed for clonal immunoglobulin gene rearrangements in 29 patients with low-grade B-cell lymphomas. 76% of the patients showed clonal rearrangements of immunoglobulin genes in their blood, including 58% of those with no other evidence of disease. In seven patients from whom paired samples were available the rearranged bands found in the blood and in lymph-node biopsy specimens containing histologically confirmed lymphoma were identical. Detection of circulating lymphoma cells by use of tumour-specific anti-idiotype antibodies and cytofluorimetry showed complete agreement with the results of DNA analysis.

B-Lymphocytes↗

Syngeneic antiidiotypic immune responses to a B cell lymphoma. Comparison between heavy chain hypervariable region peptides and intact Ig as immunogens.

The nucleic acid sequence of the heavy chain variable region (VH) expressed by 38C13, a B cell tumor of C3H origin, was determined by a combination of direct (messenger RNA) mRNA sequencing by primer extension and complementary DNA (cDNA) isolation and sequencing in M13. The VH amino acid sequence was deduced, and hypervariable regions were identified. From an analysis of predicted secondary structure, regions of predicted antigenicity were chosen, and a series of synthetic peptides corresponding to CDR2 and CDR3 (complementarity-determining region) were produced. These peptides were coupled to protein carriers and used to immunize syngeneic C3H mice. All peptides gave rise to a vigorous antibody response. However, only the CDR3 peptides induced antibodies that crossreacted with the isolated H chain protein. Only one CDR3 peptide induced antibody-producing clones, isolated as hybridomas, that reacted with the intact IgM protein. However, the appearance of these clones was a low-frequency event. All antibodies reacting with the H chain or the intact IgM protein were idiotypically specific for 38C13. These monoclonal antiidiotype (anti-Id) antibodies, raised against CDR3 peptides, gave strong reactions in enzyme-linked immunosorbent assays and immunoblots, but they were of low affinity compared to syngeneic anti-Id raised against the intact IgM protein. Moreover, while the intact IgM was capable of inducing tumor immunity, the CDR peptides were not able to do so.

Animals↗

Emergence of idiotype variants during treatment of B-cell lymphoma with anti-idiotype antibodies.

We studied two patients with malignant B-cell lymphoma that manifested resistance to the therapeutic effects of anti-idiotype antibody because of the emergence of subclones with changes in their immunoglobulin idiotypes. In both patients, tumor-cell populations arose that were unreactive with anti-idiotype antibody but that retained surface immunoglobulin. One of the patients had an additional subpopulation of tumor cells that had switched from mu to gamma heavy-chain expression. Study of the immunoglobulin genes in the tumors confirmed that the subpopulations were derived from the same original clone of neoplastic B cells in each patient. The available data suggest that the idiotypic variation observed was the result of somatic mutation in the variable region of the active immunoglobulin genes. The fact that such mutations became evident over a short time and in the context of a partial tumor response suggests that the antibody therapy exerted a strong selective force against tumor cells that expressed the idiotype determinant. Multiple anti-idiotype antibodies may therefore be needed to identify all cells of a malignant clone, and some patients may require treatment with more than one monoclonal antibody.

Adult↗

Isolation and fractionation of ferritin from human term placenta--a source for human isoferritins.

A method for isolating ferritin from human term placenta was described. The placenta was homogenized in water containing protease inhibitor and heated at 70 degrees C. The ferritin was precipitated with ammonium sulfate at pH 5.2 and purified by repeated cycles of ultracentrifugation and molecular sieve chromatography through Sepharose 4B columns. Isoelectric focusing revealed a broad spectrum of isoferritins. These isoferritins were separated by ion-exchange chromatography on Sephadex A-25 at pH 7.5 and stepwise elution with increasing concentrations of NaCl. By this method "basic," "intermediate," and "acid" isoferritins were separated. The most basic placental isoferritin was shown to be identical to splenic ferritin by isoelectric focusing, subunit analysis, and fluorescent ELISA. The acid placental isoferritin had similar characteristics to heart-type ferritin. It was suggested that the easily available placental tissue could serve as a source for human isoferritins in research and in clinical assays.

Carbonic Anhydrases↗

The optimal application of forward and ninety-degree light scatter in flow cytometry for the gating of mononuclear cells.

Peripheral blood mononuclear cells from ten normal donors were labeled with a monoclonal antibody specific for monocytes and analyzed using a fluorescence activated cell sorter (FACS). Forward and 90 degrees light scatter parameters were studied in order to apply optimal computerized gating to identify and exclude monocytes from lymphocyte populations. An average of 9.45% versus 1.22% of cells, within chosen lymphocyte gates established by forward angle and 90 degrees scatter, respectively, were identified as monocytes. In samples from ten donors, the exclusion of monocytes from the lymphocyte population was more efficient using 90 degrees scatter than forward scatter. Simultaneous use of forward and 90 degrees scatter did not significantly improve the ability to accurately exclude monocytes, but did result in a significant increase in the improper exclusion of lymphocytes. Use of 90 degrees scatter alone, forward scatter alone, and forward and 90 degrees scatter simultaneously to identify lymphoid cells resulted in the exclusion of 12, 17, and 23% of lymphocytes from further analysis. The 90 degrees scatter alone appears to be the optimal method to eliminate monocytes electronically from mononuclear cell populations in which lymphocytes are being studied.

Adult↗

Systemic candidiasis in mice immunized with Candida albicans ribosomes.

In view of our previous findings that vaccination of mice with Candida albicans ribosomes protects them against experimental systemic candidiasis, the aim of this study was to investigate the effect of this vaccination on the course of infection in immunized animals. Since the kidney is the major target in systemic candidal infection, we concentrated in this research on studying the histopathology and determining quantitatively the candidal colonization of this organ. The experiments were carried out at various time intervals after intravenous inoculation with live C. albicans. The colonization of kidneys in immunized mice was markedly lower than that in controls. The maximal difference in renal colonization between immunized and non immunized animals was observed when relatively low challenge doses were used. The inhibition of candidal multiplication in immunized mice seemed to be correlated to their increased resistance against lethal challenge, as expressed by a significantly higher survival rate. Histopathological changes and fungal elements were found in kidneys of control mice as early as 20 h post infection, while the kidneys of immunized mice did not seem affected by the disease. Moreover, even 3 days post infection, the kidneys of vaccinated animals still seemed normal. In conclusion, apparently the ribosomal vaccination leads to diminished colonization of the major site of infection in candidiasis, thus affording protection to the immunized animals against these infections.

Animals↗

Genetic variability of alkaline phosphatase expression in inbred mouse tissues.

Quantitative alkaline phosphatase (ALP; EC 3.1.3.1) expression varies among various tissues and among inbred mouse strains. There is about a 20-fold difference in ALP activity in lungs from CBA/J and C57L/J inbred strains and this difference is inherited additively with a heritability of 0.84. Studies of thermostability at 56 and 65 degrees C and sensitivity toward inhibitors (L-phenylalanine, L-homoarginine, L-phenylalanylglycylglycine, and levamisole) do not demonstrate differences in the ALP from lungs or liver of the CBA/J and C57L/J strains. The ALP activity in intestine expressed by the intestinal locus varies over 100-fold between A/J and DBA/1J strains. Further studies of the mechanisms resulting in this difference in ALP activity should help elucidate the mechanisms for aberrant expression of ALP in malignancy and for manipulation of low ALP activity in hypophosphatasia.

Alkaline Phosphatase↗