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Biomedical subjects

S Levy

Publications and source records attributed to S Levy.

At least 217 records · Page 12Linked to original sources
PubMed1987

Hypertension and indicators of coronary heart disease in Wallis Polynesians: an urban-rural comparison.

A comparative study of hypertension, and indicators of and risk factors for coronary heart disease was undertaken in samples of rural Wallisians of Wallis Island, and first generation Wallisian migrants in the urban centre of Noumea, New Caledonia. Approximately 20% of the adult population of the two communities was included in the study. Higher mean blood pressure and hypertension prevalence in Wallisians in Noumea compared to those in Wallis was documented. There was no significant rise in blood pressure with age in rural Wallisian males. Wallisians in Noumea tended to be more obese than those in Wallis (particularly females). Although differences in the extent of obesity appeared to explain some of the differences in blood pressure between populations of Wallis and Noumea, other environmental factors (such as salt intake) are probably important. There was a trend for a higher prevalence of Q wave changes on the ECG in urbanized Wallisians compared to their rural counterparts. There was no significant or consistent differences in plasma lipid concentrations between the two groups. The prevalence of diabetes was 7 and 4 times higher in Noumea compared to Wallis for males and females respectively. Differences in diabetes and hypertension prevalence are more likely to account for the variation in ischaemic heart disease than plasma lipid levels.

Adult↗
PubMed1987

A rapid method for cloning and sequencing variable-region genes of expressed immunoglobulins.

A rapid procedure is described for cloning immunoglobulin V region genes from cells that express them. cDNA is synthesized from mRNA template using primers homologous to the immunoglobulin constant-region genes. Blunt-ended, double-stranded cDNA is obtained by sequential addition of enzymes to a single tube. The cDNA is inserted directly into the M13 vector, which is screened by plaque lifting for the presence of specific inserts. Screening probes can be generated from 32P-labeled single-stranded cDNAs generated from primers different from those used for cloning, or alternatively, from previously cloned V or C gene segments. The ease of cloning a cDNA V region is directly related to the abundance of Ig-specific mRNA within the cell of interest. This method minimizes the number of steps and the time needed to obtain accurate and complete sequences of any expressed Ig V region gene.

Amino Acid Sequence↗
PubMed1987

Retention of an idiotypic determinant in a human B-cell lymphoma undergoing immunoglobulin variable-region mutation.

Tumor cells from a patient with B-cell lymphoma were fused with a mouse myeloma cell line. A set of heterohybridomas was thus derived, each of which represented a separate clonal derivative from the tumor cell population. The immunoglobulins secreted by these cell lines reacted variably with a panel of anti-idiotypic antibodies, indicating that the tumor was heterogeneous; however, one antibody, 4D6, reacted strongly with the product of all the heterohybridomas. cDNA for the immunoglobulin heavy chain variable-region genes expressed in these heterohybridomas was cloned and sequenced. Comparison of these sequences indicated that the cells expressing them were clonally related but that they had undergone considerable mutation. Despite mutation, the cells in this tumor population continued to express a functional immunoglobulin molecule and to retain, over a span of 3 years, the idiotypic determinant defined by the 4D6 monoclonal antibody. Thus a selective force existed within the host to retain tumor cells bearing an immunoglobulin molecule with a particular idiotypic structure.

Animals↗
PubMed1987

Ability of the Ca2+-selective microelectrodes to measure fast and local Ca2+ transients in nerve cells.

The ability of the Ca2+-selective microelectrode to measure fast Ca2+ transients intracellularly is reviewed. In vitro, Ca microelectrodes can respond to Ca2+ injections with time to peaks as small as 40 ms. We present methods to improve the dynamic response of Ca microelectrodes and to make Ca-buffered solutions in high ionic strength. Examples of measurements of intracellular free Ca2+ [( Ca2+]i) transients in Aplysia neurons and in Limulus photoreceptors are shown. To show the validity of those measurements, simultaneous recordings of the Arsenazo III (AIII) absorbance and of the Ca-selective electrode potential were made in voltage-clamped neurons of the abdominal ganglion of Aplysia californica. Pressure injection of AIII to a concentration of 300-500 microM induced a rise in resting [Ca2+]i; injection of higher [AIII] led to buffering of [Ca2+]i transients. Both techniques responded to changes in resting [Ca2+]i in the same direction except that AIII showed an increase in absorbance in 0 [Ca2+]o. Voltage-clamp pulses transiently increased both the AIII absorbance and the Ca2+ electrode potential. Reducing or increasing the driving force for Ca2+ entry changed the magnitude of both signals in the right direction. Examples of spatial localization of [Ca2+]i increases and Ca2+ gradients within the cytoplasm were demonstrated using the Ca electrode. The use of optical techniques to measure local [Ca2+]i changes is briefly reviewed.

Animals↗
PubMed1987

Correlation of stress factors with sustained depression of natural killer cell activity and predicted prognosis in patients with breast cancer.

Natural killer (NK) cell activity and psychological status were measured at baseline and at 3 months into treatment, as part of the National Cancer Institute (NCI) Protocol 79-C-111, randomizing breast cancer patients to lumpectomy/radiation v mastectomy. Patients who were found to have positive axillary lymph nodes also received combination chemotherapy (Adriamycin [Adria Laboratories, Columbus, OH], plus Cytoxan [Mead Johnson Pharmaceuticals, Evansville, IN] or methotrexate, plus 5-fluorouracil [5-FU]). Seventy-five patients were entered onto this behavioral immunology protocol at the time of data analysis. We reported in an earlier publication that NK activity was an important predictor of patient baseline prognosis relevant to nodal status. In that study, by using multiple regression analyses, 51% of the baseline NK activity variance could be accounted for by entering three distress indicators into the equation (patient "adjustment," lack of social support, and fatigue/depression symptoms). On reassessment of NK activity after 3 months, it was found that NK activity was not affected by the interim administration of chemotherapy and/or radiotherapy. However, consistent with our earlier findings, NK activity levels remained markedly lower in patients with positive nodes than in patients with negative nodes (at 60 to 1 effector to target cell [E:T] ratio, mean of 18% lytic activity v mean of 31% lytic activity [t = 1.87, P less than .05]). Even though average levels of NK activity were lower for patients with more tumor burden, there was still a substantial range of NK activity levels within the node positive patient group, as well as within the patient group as a whole. We hypothesized that differences in levels of NK activity could be predicted on the basis of baseline distress factors found to be significant in our earlier report. In fact, we found that we could account for 30% of NK activity level variance at 3 months follow-up on the basis of baseline NK activity, fatigue/depression, and lack of social support. Therefore, although neither radiation nor chemotherapy appeared to affect NK activity, tumor burden was again clearly associated with NK activity levels, and a significant amount of baseline and 3-month NK activity could be predicted on the basis of CNS-mediated effects. At the least, such factors provide a psychological marker of host biological status.

Adult↗
PubMed1987

Permeabilization reveals classical stimulus-secretion coupling in bovine parathyroid cells.

Unlike most secretory cells, high extracellular Ca2+ inhibits, rather than stimulates, PTH release from parathyroid cells. To gain more direct access to the potentially unique secretory apparatus of this cell type, we developed techniques for permeabilizing parathyroid cells using electroshock. Exposure of dispersed bovine parathyroid cells to five 2-kV discharges results in more than 90% uptake of trypan blue and rapid loss of intracellular 86Rb, documenting permeabilization of the plasma membrane. Unlike intact parathyroid cells, a high Ca2+ concentration increases PTH release 2.8-fold from permeabilized cells, with half-maximal and maximal stimulation at 10(-5) and 4 X 10(-4) M Ca2+, respectively, a pattern similar to classical stimulus-secretion coupling. Moreover, PTH release was low at Ca2+ concentrations equivalent to those in intact cells at low extracellular Ca2+ levels (approximately 2 X 10(-7) M). Cellular mechanisms other than changes in the cytosolic Ca2+ concentration per se, therefore, presumably mediate low Ca2+-stimulated PTH release in the intact cell. Diacylglycerol and protein kinase C may play a role in this process, since dioctanoylglycerol (10(-4) M) and 12-O-tetradecanoyl phorbol 13-acetate (10(-6) M) each enhance PTH release from permeabilized cells 2- to 4-fold at a Ca2+ concentration (approximately 2 X 10(-7) M) equivalent to that present in the intact cell at low extracellular Ca2+ concentrations.

Animals↗
PubMed1986

Self-help group behavioural treatment for obesity. An evaluation of Weight Control Workshops.

A study of a self-help weight control programme (Weight Control Workshops) in Sydney followed 168 women and four men from the beginning of the 12-week programme until six months after the end of the programme. The average subject was a 42-year-old woman who was moderately overweight with a starting weight of 74 kg and wished to lose 13 kg. Although 90% of subjects lost weight during the programme, weight losses were modest, with a mean loss of 4.3 kg. Weight loss was not well maintained, with 52% gaining weight in the follow-up period, to give a mean weight gain of 0.4 kg. The Weight Control Workshop programme represents a group treatment for obesity based on standard behaviour therapy, and appears to be as effective as similar programmes that have been reported in the literature.

Behavior Therapy↗
PubMed1986

Idiotype variant cell populations in patients with B cell lymphoma.

Using isolated idiotype (Id) protein we generated panels of antibodies in two patients with follicular lymphoma, one of whom had never received prior chemo-or radiotherapy. Flow cytometry and frozen section tissue staining of tumor with these monoclonal antibodies (mAb) revealed multiple subpopulations within each tumor. Individual mAb stained between 7% and 83% of surface Ig+ cells in the tumor samples. These subpopulations were overlapping and no single antibody recognized all the tumor cells. However, combinations of antibodies seemed to capture total tumor in both cases. In some instances, the percentage of tumor stained by a single mAb varied over time, and differed between lymph nodes sampled at the same time. Because a single species of Id protein was used to generate mAb in each case, it appears that the antibodies were directed against idiotopes variably shared by different populations within each tumor, and this was confirmed by crossblocking studies. Tumor cells from one patient were fused to a nonsecreting heteromyeloma line K6H6/B5, and most of the resulting hybrids secreted Id protein. Four mAb were used to screen the Id proteins secreted by these hybrids, and 11 different variants (16 maximal) were found. Southern blot analysis of rearranged Ig genes was done in two hybrids and biopsy material. Identically rearranged light-chain genes were seen but it appeared as though extensive somatic variation had occurred in heavy chain genes. These studies indicate that: striking Id variation can exist at diagnosis in untreated patients, the percentage of tumor represented by an individual variant may change with time and may differ between tumor sampled from different anatomical locations, and somatic variation appears to be responsible for the observed heterogeneity. Although this degree of variation makes anti-Id antibody therapy more difficult, appropriate combinations of mAb should be more efficacious than single antibodies in such cases.

Adult↗
PubMed1986

Clustering of extensive somatic mutations in the variable region of an immunoglobulin heavy chain gene from a human B cell lymphoma.

Following treatment of a human B cell lymphoma with an anti-idiotype antibody, a subpopulation of tumor cells remained that had lost the tumor-specific heavy chain idiotypic determinant. Nucleotide sequence analyses of eight independent heavy chain variable region isolates showed extensive point mutations, so that no two sequences were identical. Comparison of pretreatment and posttreatment sequences implicated an amino acid in CDR2 as being involved in the idiotypic determinant. Apparently the malignant B cells escaped the therapeutic effects of the anti-idiotype antibody through an ongoing process of somatic mutation in their immunoglobulin genes. Non-random clustering of amino acid replacements in CDR2 suggested that growth of the tumor may have been influenced by endogenous selective forces interacting with the tumor cell-surface immunoglobulin.

Amino Acid Sequence↗
PubMed1986

A controlled neuropsychological comparison of Huntington's disease and multiple sclerosis.

This study compared the intellectual deficits of patients who had the earliest stages of Huntington's disease (HD) with those of mildly or moderately affected patients suffering from multiple sclerosis; both groups were matched for age, education, and ability to function. Twenty-one HD patients, 30 multiple sclerosis subjects, and 15 matched controls were evaluated neuropsychologically; all were free of psychoactive medications. The two patient groups showed similar overall patterns of impairment, though the HD group had greater verbal and nonverbal memory deficits. The HD patients also demonstrated significant dyscalculia and showed indications of developing problems in language usage and copying. These results are discussed in light of each disorder's neuropathologic substrate.

Adult↗
PubMed1986

Sequential cholinesterase tests and symptoms for monitoring organophosphate absorption in field workers and in persons exposed to pesticide spray drift.

Pre-season, in-season and post-season cholinesterase (ChE) levels (Ellman method) were monitored in 36 field workers (sprayers, field hands, leaf inspectors) from 3 kibbutzim and 25 residents from the same kibbutzim. Small and presumably inconsequential in-season reductions in plasma and whole blood ChE activity were seen in field workers and residents exposed to spray drift, but not in non-exposed residents. Intra- and inter-individual variability in plasma and whole blood ChE activities were within 'normal' ranges (e.g., less than 30% inhibition), but the variability (intra- and inter-individual) was greater in the field workers compared with residents. Daily logs from the infirmary of one kibbutz for 1 month recorded an excess of complaints (respiratory tract, eye irritation, headache) in residents on days when organophosphates were sprayed from aircraft compared to days when other or no pesticides were sprayed. The findings provide some indications of the utility and the level of sensitivity of plasma ChE for monitoring field workers, and possibly residents exposed to drift. Selective semi-routine examinations of alkylphosphates in urine together with the assessment of health effects are recommended to determine whether or not ChE monitoring is needed on a routine basis, or should be replaced by alkylphosphate monitoring.

Adolescent↗