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Biomedical subjects

R Levy

Publications and source records attributed to R Levy.

At least 487 records · Page 27Linked to original sources

Platelet and erythrocyte membrane changes in Alzheimer's disease.

Previous reports have suggested that the physical properties of cell membranes and calcium homeostasis in both the central and peripheral nervous system are changed in Alzheimer's disease (AD). This study has examined the biophysical properties of erythrocyte and platelet membranes by measuring the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and possible related changes in lipid peroxidation. In addition, we have studied calcium homeostasis by measuring thrombin-stimulated changes in intraplatelet free calcium and Ca2(+)-ATPase activity in AD and healthy age and sex-matched controls. Our results show that there was no significant difference in the fluorescence anisotropy of DPH in erythrocyte membranes isolated from the three groups. There was also no significant difference in lipid peroxidation levels in erythrocytes and plasma of AD patients compared to controls. However, there was a significant reduction in the fluorescence anisotropy of DPH in platelet membranes from AD patients, compared with healthy controls. Recent evident suggests that the increase in platelet membrane fluidity results from alterations in internal membranes. We measured the specific activities of enzyme markers associated with intracellular and plasma membranes in platelets from AD patients and healthy controls. There was a significant reduction in the specific activity of antimycin A-insensitive NADH-cytochrome-c reductase (a specific marker for smooth endoplasmic reticulum (SER)), in AD patients compared to controls, but no change in the specific activity of bis(p-nitrophenyl)phosphate phosphodiesterase (a specific marker for plasma membrane). We have also shown that SER mediated [Ca2+] homeostasis is possibly impaired in AD platelets, i.e., the percentage of thrombin-stimulated increase in intraplatelet [Ca2+] above basal levels was significantly higher in AD compared to matched controls and there were significant reductions in the specific activities of Ca2+/Mg2(+)-ATPase and Ca2(+)-ATPase (but not Mg2(+)-ATPase) in AD platelets. Finally electron microscopic analysis of platelets showed that there was a significant increase in the incidence of abnormal membranes in AD patients compared to controls. The ultrastructural abnormalities seem to consist of proliferation of a system of trabeculated cisternae bounded by SER. These results suggest that both SER structure and function might be defected in AD platelets, which could explain the fluidity changes observed here.

Alzheimer Disease↗

After the asylums.

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Community Mental Health Services↗

Directional cloning of cDNA using a selectable SfiI cassette.

To increase the efficiency of directionally cloning cDNA, we have constructed a pair of vectors and devised a cDNA cloning strategy that improves upon previously published methods. The vectors, pLIB: AZ and pLIB: ZA, have two unique (distinct religation specificities; GGCCN/NNNNGGCC) SfiI sites (SfiI.A and SfiI.B) flanking a stuffer fragment which contains the tetracycline-resistance element. These vectors permit the directional cloning of cDNA in both sense (pLIB: AZ) and antisense (pLIB: ZA) orientations relative to the promoter for phage T3 RNA polymerase. cDNA that was synthesized using a primer with a 5' sequence of a SfiI.B site followed by an oligo(dT)16 3' tail was then ligated to an adaptor with the sequence of a SfiI.A site produced directional molecules that could be cloned into the pLIB vectors. Complex libraries with 10(7) members were produced from as few as 6 x 10(5) cells. The SfiI sites and stuffer can be subcloned as a cassette to permit directional cloning in other vectors, as there are several restriction enzyme sites flanking this region to the 5' and 3'.

Base Sequence↗

Specific binding of placental acidic isoferritin to cells of the T-cell line HD-MAR.

Acidic placental isoferritin inhibited the blastogenic response of peripheral human lymphocytes to T-cell activating lectins. We measured specific binding of radioiodinated placental isoferritin to cells of the T-cell line HD-MAR and found specific high-affinity binding. Binding was faster and more ferritin was bound at 37 degrees C than at 4 degrees C. Displacement experiments indicated that most of the binding occurred at the cell surface. Acidic placental ferritin and isolated H-type ferritin subunits but not isolated L-type subunits, competed for the binding. Scatchard plot analysis showed characteristics of a single binding species with a dissociation constant (Kd) of 1.3-4.4 x 10(-11) M. The results suggest the presence of receptors for acidic isoferritin on T-lymphocytes and thus, a regulatory role for the acidic ferritin H-type subunit in T-cell function.

Binding, Competitive↗

Induction of proliferation of human follicular (B type) lymphoma cells by cognate interaction with CD4+ T cell clones.

We examined stimuli which are required for the induction of in vitro proliferation of follicular lymphoma cells, a low grade non-Hodgkin's B cell lymphoma characterized by a specific chromosomal translocation, t(14;18)(q32;q21), and by in vivo growth of the lymphoma cells in germinal center-like follicles infiltrated with CD4+ T cells. The purified follicular lymphoma cells, which are morphologically uniform, small, and dense, did not respond to stimulation with soluble lymphokines in the absence of T cells. Vigorous in vitro proliferation of follicular lymphoma cells was induced, however, when the follicular lymphoma cells were cultured with a CD4+ T cell clone which recognized alloantigens expressed by the lymphoma cells. This response required B-T cell contact, and was inhibited by anti-class II but not by anti-class I MHC mAb, indicating that these neoplastic B cells behaved as normal B cells and responded to normal activation and differentiation signals from T cells. After the cognate B lymphoma-T cell interaction occurred in culture, addition of IL-2 or IL-4 enhanced the proliferation of the tumor cells. These results, with a monoclonal and homogeneous population of B cells, affirm the idea that cognate interaction between B cells and Th cells is required for the effective activation of resting B cells. Moreover, these results suggest that a critical host-tumor interaction occurs in vivo, and that the polyclonal CD4+ T cells that infiltrate follicular lymphomas play a role in sustaining rather than inhibiting tumor growth in vivo. If so, therapies directed not only against the neoplastic cell but also against specific T cells and their cognate interactions with tumor cells may have a rationale.

B-Lymphocytes↗

Stimulation of the respiratory burst in peripheral blood monocytes by lipoteichoic acid. The involvement of calcium ions and phospholipase A2.

Lipoteichoic acid (LTA) from Streptococcus faecalis stimulates the respiratory burst in peripheral blood monocytes (mon), as measured by cytochrome C reduction. The effect of LTA was time and dose dependent. LTA stimulated the respiratory burst in a biphasic manner within a range of 1 to 1000 ng/ml.10(6) mon, with maximal activity at 50 ng/ml. At this concentration LTA increased the activity from 0.97 +/- 0.2 to 4.88 +/- 0.2 nmol.10(6) mon/20 min. The role of calcium ions in the effect of LTA in stimulating respiratory burst was studied by changing the availability of calcium ions in the medium, and by measuring the effect of LTA on 45Ca2+ uptake and on intracellular Ca2+ levels. Removal of extracellular calcium ions in the presence of the calcium chelator EGTA, abolished the LTA-stimulated respiratory burst. LTA (50 ng/ml) was found to increase 45Ca2+ uptake into monocytes within seconds (from 2200 +/- 242 in the untreated cells to 4642 +/- 365 cpm/min in the LTA-treated mon). At this concentration, LTA stimulated an immediate rise in the intracellular free Ca2+ concentration to 155 +/- 15 nM as compared with 120 +/- 14 nM in the unstimulated monocytes. LTA caused a specific release of arachidonic acid indicating the involvement of phospholipase A2 in the transduction signal stimulating the respiratory burst by LTA.

Antigens, Bacterial↗

[Mandibular metastases from colonic adenocarcinoma].

Metastases to the mandible are very rare and account for only 1% of all oral tumors. The most common primary in such cases is the breast. Only 20 cases of metastases to the mandible of tumors of the large bowel have been reported. We present the case of a 59-year-old woman with metastatic disease of the mandible in whom the primary tumor was an adenocarcinoma of the sigmoid. Metastases to the oral cavity and mandible should be included in the differential diagnosis of gingival or mandibular lesions in a patient with a previous or current malignancy.

Adenocarcinoma↗

Idiotypic variation in a human B lymphoma cell line.

The Ig Id of a B cell lymphoma serves as a distinct marker of the malignant clone and thus as a tumor-specific target for antibody therapy. Somatic variation of the Ig genes expressed by B cell tumors can lead to loss of reactivity with anti-Id antibodies and escape of tumors from the therapeutic effects of such antibodies. In our study, we have used anti-Id antibodies to screen for variants within a cell line derived from a patient with a large cell lymphoma of the B cell type. Cells were simultaneously stained on their surface for idiotypic and for isotypic Ig determinants using reagents labeled with different fluorochromes. Tumor cells expressing intact Ig molecules with alteration of their idiotypic determinants were isolated with the fluorescence activated cell sorter. Idiotypic variation was an ongoing process in vitro with Id- variants being generated at a rate of 2.7 x 10(-4)/cell per generation and Ig- cells being produced at a rate of 1.31 x 10(-5)/cell per generation. Subcloned variants expressed subtle differences in reactivity with a panel of three non-cross-blocking anti-Id antibodies. Analysis of Ig gene rearrangements by the Southern blotting technique using a JH probe established that the variants and the original tumor cells were all clonally related. Immunoprecipitation of surface labeled Ig molecules from the variant subclones disclosed major alterations of the lambda-L chains with no gross alterations of the mu-H chains. Related studies have established that the tumor cells undergo rearrangement and expression of new lambda-L chain genes.

Antibodies, Anti-Idiotypic↗

Sparing of attentional relative to mnemonic function in a subgroup of patients with dementia of the Alzheimer type.

Patients with dementia of the Alzheimer type (DAT) received two tests of visual selective attention, together with tests of spatial and visual recognition memory and visuospatial conditional learning previously used to show deficits early in the course of DAT. One set of attentional tests compared visual discrimination learning along intra- and extra-dimensional shifts, using a "total change" design. In the 12 DAT patients capable of attempting the extra-dimensional shift (subgroup 1), performance was equivalent to that of controls. This subgroup was also unimpaired at simple and compound discrimination learning and reversal and an intra-dimensional shift. They were as accurate as controls on a visual search task requiring matching of stimuli on two dimensions with variable numbers of alternatives, but were significantly impaired in the tests of recognition memory and learning. By contrast, the other 13 patients showed marked impairments in the attentional tasks. This subgroup was also significantly worse than subgroup 1 in performance on the visual recognition and conditional learning tasks, and showed greater severity on most of the clinical ratings of dementia. The sparing of attentional shifting in patients early in the course of DAT is contrasted with the impairments previously described in patients with Parkinson's disease with only mild or absent memory loss. The implications of this double dissociation of deficits for understanding the neural bases of the cognitive deficits in these two neurodegenerative diseases are discussed and their significance for the staging of DAT is considered.

Aged↗

Detection and typing of human papillomavirus DNA from cervical biopsies by the slot-blot hybridization method.

Cervical biopsies collected from 105 consecutive patients participating in a prospective follow-up study for cervical human papillomavirus (HPV) infections were tested for the presence of HPV 6, 11, 16 and 18 DNA by the slot-blot hybridization method. Detectable HPV types 6 and 11 could be distinguished in high stringency hybridization assay. The overall HPV-DNA detection rate was 35.2% in our group of patients. The slot-blot technique is more rapid than Southern-blotting procedure and well suited for analysis of multiple specimens.

Biopsy↗

Trends of PCB, hexachlorobenzene, and beta-benzene hexachloride levels in the adipose tissue of the U.S. population.

Results are presented on the levels of selected toxic chemicals in the adipose tissue of the U.S. population. Estimates of baseline levels and time trends are presented for the chemicals beta-benzene hexachloride (beta-BHC), hexachlorobenzene, and polychlorinated biphenyls (PCBs). The statistical analyses are based on chemical data obtained from analysis of tissue specimens collected from a nationally representative sample of autopsied cadavers and surgical patients by EPA's National Human Adipose Tissue Survey during the period 1970 through 1983. The results show that while nearly the entire U.S. population has detectable levels of these chemicals, the actual concentration levels of beta-BHC and PCBs are steadily decreasing and the levels of HCB are remaining fairly constant. Comparisons of levels across demographic subpopulations show that there are some differences in concentration levels across geographic regions, age groups, and race groups.

Adipose Tissue↗

Neuropsychological deficits and CT scan changes in elderly depressives.

A number of computerized tests were used to study visual attention, memory and learning in elderly depressed patients. Impairment was found in approximately 70% of depressed patients and was seen particularly in memory and in measures of latency. Depressed patients showed equivalent impairment in short-term memory but less impairment in conditional associative learning compared to a group of patients with early dementia of the Alzheimer-type (DAT), matched for age and pre-morbid IQ. With respect to qualitative differences between depression and DAT, depressed patients showed a different pattern of errors and a consistently prolonged latency of response which was independent of delay in a delayed matching-to-sample test. On recovery from depression, although improvement was seen in most test scores, performance in measures of latency and in a number of tests of memory and learning failed to reach the level seen in a group of matched control subjects and approximately 35% of patients continued to show impairment. For the depressed patients, ventricular brain ratio (VBR) correlated with measures of slowing. In addition, in the 'recovered-depressives', VBR correlated with poor performance at high levels of task difficulty. These findings are discussed with respect to previous literature on the pattern of cognitive impairment and CT scan findings in depression.

Aged↗

Behavioral abnormalities and psychiatric symptoms in Alzheimer's disease: preliminary findings.

Behavioral abnormalities and psychiatric symptoms were assessed in 178 patients diagnosed as having Alzheimer's disease by NINCDS/ADRDA criteria. The subjects were selected from a defined catchment area and therefore were representative of a group of patients with Alzheimer's disease of varying severity. Auditory hallucinations were found in 10%, visual hallucinations in 13%, and delusions in 16%. Symptoms suggestive of depression were reported by 39% of the patients and features of depression observed in 25%. Twenty percent were aggressive, and 7% were sexually disinhibited. Nineteen percent exhibited excessive walking behavior and 10% binge eating. Nearly 50% of the sample were incontinent. Patients in the hospital were more often aggressive, incontinent, and seemingly less depressed. Patients with severe dementia displayed excessive walking behavior, were more likely to be incontinent, and reported less depressive symptoms than those with moderate or mild dementia.

Activities of Daily Living↗

Diversity in peritoneal macrophage response of CAPD patients to 1,25-dihydroxyvitamin D3.

A major complication of continuous ambulatory peritoneal dialysis (CAPD) is peritonitis. Increasing the activity of the peritoneal macrophages, the predominant cell type found in the peritoneal cavity, may be a promising treatment for this infection. The effect of 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] on the activity of peritoneal macrophages from CAPD patients and nonuremic controls was studied. 1,25(OH)2D3 had a biphasic effect on superoxide generation in the concentration range of 2.5 10(-9) M to 5 x 10(-6) M with a peak at 2 x 10(-8) M. The addition of 2 x 10(-8) M 1,25(OH)2D3 to nonuremic control macrophages for 24 hours caused a significant twofold increase in superoxide generation in response to phorbol myristate acetate (PMA), from 2.21 + 0.2 to 4.1 + 0.2 nmol/10(6) mac (P less than 0.001), and enhanced the bactericidal activity from 60 + 7% to 85 + 9% (P less than 0.005). CAPD patients were divided into two groups: Group A, patients with high peritonitis incidence (HPI); group B, patients with low peritonitis incidence (LPI). Macrophages from HPI patients show a lower bactericidal activity (37 +/- 5%) and were not affected by 1,25(OH)2D3 after 24 hours of treatment. The increase in macrophage activity was seen only after three days of incubation with the hormone. Macrophages from this group generated a high amount of prostaglandin E2 (PGE2) during the first 24 hours in culture (7.8 +/- 0.52 ng/ml as compared with 0.35 +/- 0.03 ng/ml in the controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗

Cause of death in Alzheimer's disease.

Bronchopneumonia was the commonest cause of death in 84 elderly patients suffering from Alzheimer's disease. The cause of death as stated on the death certificate agreed with the pathological diagnosis in 77% of cases. In 30%, no mention of the presence of a dementia syndrome was recorded on the death certificate. An increased willingness to record the presence of a dementia syndrome and a higher autopsy rate would increase the accuracy of death certification in Alzheimer's disease.

Aged↗