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Biomedical subjects

S Levy

Publications and source records attributed to S Levy.

At least 19 recordsLinked to original sources

The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules.

CD19 is a member of the Ig superfamily expressed on the surface of B lymphocytes that may be involved in the regulation of B cell function. Immunoprecipitation studies with B cell lines solubilized by digitonin have shown CD19 to be part of a multimolecular complex that includes CD21 (CR2) and other unidentified proteins. In this study, two of the CD19-associated proteins were identified as TAPA-1, which is expressed on most cell types, and Leu-13, which is expressed on subsets of lymphoid cells. TAPA-1 and Leu-13 are physically associated in many cell lineages. CD19 and CD21 mAb each specifically coprecipitated proteins of the same size as those precipitated by TAPA-1 and Leu-13 mAb from B cell lines and cDNA-transfected K562 cell lines. Western blot analysis with a TAPA-1 mAb verified the identity of TAPA-1 in CD19 and CD21 immunoprecipitated materials. In addition, when TAPA-1 or Leu-13 were crosslinked and patched on the cell surface, all of the CD19 comigrated with TAPA-1 and some of the CD19 comigrated with Leu-13. Furthermore, mAb binding to CD19, CD21, TAPA-1, and Leu-13 on B cell lines induced similar biologic responses, including the induction of homotypic adhesion, inhibition of proliferation, and an augmentation of the increase in intracellular [Ca2+] induced by suboptimal cross-linking of surface Ig on B cell lines. Together, these data suggest that TAPA-1 and Leu-13 are broadly expressed members of a signal transduction complex in which lineage-specific proteins, such as CD19 and CD21, provide cell-specific functions.

Antigens, CD

Alterations in septohippocampal cholinergic innervations and related behaviors after early exposure to heroin and phencyclidine.

Mice were exposed to diacetylmorphine (heroin) or phencyclidine (PCP) prenatally or neonatally. At a later age, they were tested for hippocampus-related behavioral deficits and concomitant alterations in the septohippocampal cholinergic innervations. Actually, this is an application of the previously established phenobarbital neuroteratogenicity model to heroin and PCP. Prenatal exposure was accomplished transplacentally by injecting the mother 10 mg/kg heroin or PCP on gestation days 9-18. Neonatal administrations were applied directly by injections of 10 mg/kg of either drug to the pups between neonatal days 2-21. At the age of 50 days, mice exposed to heroin and PCP prenatally exhibited a 107% and 159% increase in their muscarinic cholinergic receptors Bmax, respectively. Neonatal exposure to heroin or PCP caused an 83% and 76% increase in the receptors respectively. On the behavioral level, both prenatal and neonatal exposure to heroin or PCP reduced performance in the hippocampus related eight-arm maze and Morris mazes. Depending on the drug, the test and the period of drug administration, the reduction ranged between 10% and 75%. The results suggest that heroin and PCP induce alterations in the septohippocampal cholinergic innervations and in related behavioral performance. Further studies are necessary in order to connect the biochemical and behavioral events in causal relationships.

Aging

Expression of TAPA-1 in preimplantation mouse embryos.

TAPA-1 is a member of a new family of evolutionarily conserved transmembrane proteins which may be involved in regulation of cell growth and/or cell signalling. We have examined the temporal pattern of TAPA-1 RNA expression during mouse development. Using a sensitive reverse transcription/polymerase chain reaction assay, we show that TAPA-1 RNA is present in oocytes, fertilized eggs and cleavage stage embryos.

Animals

Use of family specific leader region primers for PCR amplification of the human heavy chain variable region gene repertoire.

We have designed a set of six, non-degenerate oligonucleotide primers, corresponding to the 5' leader regions of each of the six human VH gene families. A general strategy for family specific polymerase chain reaction amplification is described using these primers and a conserved 3' primer corresponding to frame work 3, JH, or constant region. This strategy was used to isolate and sequence novel human germline VH genes belonging to the VH2 and VH4 families. Under certain conditions, chimeric VH sequences were created by a "jumping polymerase chain reaction", combining DNA segments from different germline genes, but this could be avoided by limiting the number of amplification cycles. PCR amplification with these family specific primers will facilitate studies of the repertoire of germline VH genes as well as studies on VH gene usage in normal and aberrant (B cell malignancies, autoimmune diseases, etc.) B cell populations.

Amino Acid Sequence

Modulation of human natural killer cell activity by exposure to uncontrollable stress.

Changes in natural killer cell (NK) activity and proportions of circulating T and NK lymphocyte subsets were assessed in adult males immediately after exposure to controllable or uncontrollable stress (noise) as well as 24 and 72 h later, in order to track the time course of the effects of stress. The role of control-relevant personality variables as moderators of the stress-immunosuppression relationship was considered. Subjects who perceived they had control over the noise as well as no-noise "control" subjects showed no reduction in NK activity. By contrast, subjects who perceived that they had no control over the stressor showed reduced NK activity immediately after the conclusion of the first 20-min stress session, and the reduced NK activity was found as long as 72 h later. Optimism and one's desire to be in control enhanced the negative impact of uncontrollable noise on NK activity. No differences between conditions were found on number of NK cells or a variety of T cell subsets. The results suggest the importance of perceived control in moderating the short- and long-term effects of stress on NK activity.

Adolescent

Synthesis, assembly and function of plant cell wall macromolecules.

The plant cell wall consists of a structurally intricate network of polysaccharide and protein whose biosynthesis, assembly and functions are still poorly understood. Recent research has shown how cell wall macromolecules, and fragments thereof, appear to be involved in processes such as cell growth, cell and tissue differentiation and the control of pathogenesis.

Cell Wall

Adolescent suicide attempts: outcomes at follow-up.

Adolescents seen in a general hospital emergency department or psychiatrically hospitalized were followed up at one month and three months following a suicide attempt. Findings included substantial drop-out rates for psychotherapy and high rates of repeated suicide attempts by three months. Implications for disposition planning and care of such adolescents are discussed.

Adolescent

Inferring articulation and recognizing gestures from acoustics with a neural network trained on x-ray microbeam data.

This paper describes a method for inferring articulatory parameters from acoustics with a neural network trained on paired acoustic and articulatory data. An x-ray microbeam recorded the vertical movements of the lower lip, tongue tip, and tongue dorsum of three speakers saying the English stop consonants in repeated Ce syllables. A neural network was then trained to map from simultaneously recorded acoustic data to the articulatory data. To evaluate learning, acoustics from the training set were passed through the neural network. To evaluate generalization, acoustics from speakers or consonants excluded from the training set were passed through the network. The articulatory trajectories thus inferred were a good fit to the actual movements in both the learning and generalization conditions, as judged by root-mean-square error and correlation. Inferred trajectories were also matched to templates of lower lip, tongue tip, and tongue dorsum release gestures extracted from the original data. This technique correctly recognized from 94.4% to 98.9% of all gestures in the learning and cross-speaker generalization conditions, and 75% of gestures underlying consonants excluded from the training set. In addition, greater regularity was observed for movements of articulators that were critical in the formation of each consonant.

Adult

[Slow ventricular tachycardia caused by naftidrofuryl overdose (naftidrofuryl and ventricular tachycardia)].

Treatment with intravenous naftidrofuryl may be complicated by ventricular arrhythmias. A case of slow ventricular tachycardia occurring in a 65-year-old man with a dilated cardiomyopathy following an accidental overdose of naftidrofuryl (2 x 200 mg ampules in 250 ml of 5% glucose solution in 2 hours) prescribed for complicated arterial disease of the lower limbs is reported. This sustained ventricular tachycardia converted spontaneously after several hours. This case emphasises the risk of arrhythmogenic effects of this drug and indicates the need for careful monitoring when it is used intravenously in patients with underlying heart disease.

Aged

The effects of recombinant human erythropoietin on the cell mediated immune response of renal failure patients.

Recombinant human erythropoietin (rHuEpo) is now widely employed in correction of the anemia of end stage renal disease (ESRD). Recent reports suggest that rHUEpo, in addition to its effect on CFU-E and burst-forming-unit-erythroid (BFU-E), may stimulate granulocyte/macro-phage production and pluripotential progenitors of the myeloid and monocyte lineage. Furthermore, there is now data which demonstrate that ESRD patients who received rHuEpo have enhanced cytokine production. Taken together, these observations suggest that the administration of rHuEpo may augment the diminished immune response of renal failure patients. To evaluate the effects of rHuEpo therapy on cell-mediated immunity in hemodialysis patients, a prospective controlled study was conducted. Two parameters of immune function were tested. One was natural killer cell (NK) activity, and the other proliferation in response to the T cell mitogen concanavalin A (Con-A). NK activity of the ESRD patients was comparable with that of normal controls at the start of the study and was unaffected by rHuEpo therapy. In contrast to this, anemic ESRD patients initially demonstrated impaired mitogen driven proliferation (initial stimulation index (S.I.) = 42.5 +/- 11.9) which significantly improved following rHuEpo therapy (final S.I. = 73.3 +/- 14.7, p < 0.05). The later value exceeded the mitogen response in less anemic ESRD patients who did not receive rHuEpo (initial S.I. = 60.7 +/- 16.5, final S.I. = 61.0 +/- 16.7), but did not reach values seen in normal controls. The data suggest that rHuEpo therapy may be associated with enhanced immune responses in patients with ESRD.

Aged

Prevalence of anaemia and iron deficiency at different levels of urbanization in Vanuatu.

Mean haemoglobin and plasma iron levels and prevalences of anaemia and iron deficiency were determined in three population samples of Vanuatuans aged 20 or more years as part of a noncommunicable diseases survey in 1985. The three samples were drawn from separate urban, semirural and rural populations. Age-adjusted mean haemoglobin levels were highest in the urban sample and lowest in the rural sample, and plasma iron levels were highest in the urban sample and lowest in the semirural sample. Mean values in each location were generally higher in male subjects than in nonpregnant female subjects. The overall prevalence of anaemia was 10.1% in nonpregnant female subjects and 5.3% in male subjects by World Health Organization (WHO) definitions. These prevalences are lower than those reported for most other developing countries, including some Pacific island nations. Iron deficiency was more prevalent in females than in males (females 17.2%; males 5.0%). Approximately 40% of anaemic subjects were also iron deficient, and there was a significant positive correlation of plasma iron levels with haemoglobin concentration. This suggests that haemoglobinopathies may not be a major cause of anaemia as previously reported. Although most anaemic subjects (88%) had only mild anaemia, in view of the physical lifestyle of rural and semirural Vanuatuans it would be important to optimize haemoglobin levels in these populations.

Adult

The effect of physician and patient gender on preventive medicine practices in patients older than fifty.

This study examined whether the sex of physicians and patients affected the preventive care of middle-aged and older patients of family physicians. The charts of 61 male and 75 female patients older than 50 years, whose primary physicians were third-year family practice residents, were reviewed to determine whether tests to screen for colorectal, breast, and cervical cancer had been offered to them in the previous 18 months by their primary physicians. Male residents had offered rectal examinations significantly more frequently than female residents to male patients older than 70. Female residents had offered mammograms, pelvic exams, and Pap smears significantly more frequently to women older than 50 than had male residents. Female residents had significantly higher rates of offering pelvic exams and Pap smears to women between the ages of 50 and 70, but this difference was not significant for women over 70. There were no significant differences in the number of refusals by male or female patients to male or female residents. Results suggest that the sex and age of the patient and the sex of the physician may play a role in differential rates of cancer screening.

Aged

Effect of intracellular injection of inositol trisphosphate on cytosolic calcium and membrane currents in Aplysia neurons.

Pacemaker cells of Aplysia californica display a regular bursting that results from a complex interplay of Ca(2+)-mediated conductances and a continuous influx and extrusion of Ca2+. The effect of the second messenger 1,4,5-inositol trisphosphate (InsP3) on intracellular free Ca2+ concentration (Cai) regulation and electrical properties was investigated in identified neurons of the abdominal ganglion (R15, L2-L4, L6). Double-barreled Ca-selective microelectrodes were used to pressure inject InsP3 and measure Cai at the same point. Brief injection of InsP3 resulted in an average increase of Cai of 9.2 +/- 10.0 microM (+/- SE; n = 14) that decayed in about 1 min. The InsP3-induced elevation of Cai increased in a dose-dependent manner and saturated when large amounts of InsP3 were injected. The InsP3-induced Cai increase was the result of mobilization from intracellular stores; Cai could be repeatedly mobilized by InsP3 in cells superfused with 0 Ca artificial seawater for more than 60 min. Following multiple injections of InsP3, there was no evidence of immediate inhibition or facilitation. the spatial nature of the InsP3-induced Cai increase was investigated by moving the double-barreled Ca-selective microelectrode tip in a stepwise manner relative to the membrane surface. The largest InsP3-induced Cai increases were measured in an area 0-80 microns from the membrane surface; some cells had their largest InsP3-induced Cai increase some 120-160 microns away from the membrane. Injection of InsP3 in a bursting neuron induced an immediate train of action potentials followed by membrane hyperpolarization and a decrease in the burst frequency. Injection of InsP3 in voltage-clamped cells induced a biphasic response: a rapid inward current followed by a more prolonged outward current; the temporal overlap of the currents was depth dependent. Injection of InsP3 or Ca2+ from a double-barreled injecting electrode induced currents that were different in waveform and time course, indicating that part of the conductance change induced by InsP3 is direct and not mediated by the mobilized Ca2+. In BAPTA [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'tetra-acetic acid]-loaded cells, the InsP3-induced inward current was mostly unaffected while the Ca-induced outward current was largely attenuated. The results suggest that InsP3 mobilizes Ca2+ from discrete intracellular compartments and induces distinct changes in membrane currents that seem to be independent of the Cai increase.

Animals

Vascular and cardiac reactivity in pulmonary hypertension due to chronic obstructive lung disease: assessment with various oxygen concentrations.

The aim of the present work was to evaluate vasoreactivity in patients with pulmonary hypertension related to chronic obstructive lung disease. This was done by comparing haemodynamic data recorded while patients were breathing room air, and hypoxic and hyperoxic mixtures. We estimated the role of vasoconstriction in determining the level of pulmonary hypertension. This study included 26 patients with moderate pulmonary hypertension mean pulmonary arterial pressure (MPAP) = 27.3 +/- 1.2 mmHg) secondary to chronic obstructive lung disease (COLD), forced expiratory volume in one second (FEV1) = 0.95 +/- 0.13 l; arterial oxygen tension (PaO2) = 8.7 +/- 0.25 kPa). After insertion of a thermodilution catheter in the pulmonary artery and a cannula in the femoral artery, mixtures containing 15, 21, 30 and 100% oxygen were randomly administered for 20 min each. As fractional inspiratory oxygen (FIO2) increased, MPAP decreased relatively less than cardiac index. Cardiac output was at its highest during room air breathing and the hypoxic mixture did not lead to a further increase. Unlike normal subjects, in whom adjustment of cardiac output is achieved by heart rate alone, haemodynamic regulation in these patients also involved stroke volume. Variations in MPAP and cardiac index were strongly correlated with arterial oxygen saturation (SaO2). The greatest variations were noted in the patients with the highest pulmonary hypertension. Under normoxic and hyperoxic condition the relationship between pulmonary artery driving pressure and cardiac index was linear and its slope steeper in patients having the highest pulmonary hypertension at steady-state.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Ig VH gene expression among human follicular lymphomas.

Thirty-six randomly selected cases of low grade follicular lymphoma (FL) were analyzed for Ig heavy chain variable region (VH) gene expression. Assignment to one of the six human VH gene families (VH1 to VH6) was made with a polymerase chain reaction-based technique using family-specific leader primers. The frequency of VH family use in FL was found to be similar to that reported for normal peripheral blood lymphocytes and is therefore also roughly proportional to VH family size. To evaluate expression within an individual family, all of the lymphoma VH genes from the middle size VH4 family were sequenced and compared with previously published sequences. Of these eight lymphoma VH sequences, six were most closely related to just two of the 10 known functional VH4 germline genes. Nonrandom usage by FL of the JH3, JH4, and JH5 joining segments was also observed. Nucleotide sequences were also determined for 10 randomly selected lymphoma VH genes from the large VH3 family. With one possible exception, none of these lymphoma VH sequences appear to represent any of the VH3 genes that may be preferentially used in the fetal repertoire.

Base Sequence

Structure and membrane topology of TAPA-1.

TAPA-1 (the target of an antiproliferative antibody) is a 26-kDa cell surface protein expressed on most human cell lines. TAPA-1 is a member of an evolutionarily related family of cell surface proteins all of which contain four transmembrane domains. A model is proposed for topology of TAPA-1 based on proteolysis studies in the in vitro translated protein embedded into microsomal membranes. This analysis predicts that the amino and the carboxyl termini of the molecule are cytoplasmic and that the two hydrophilic regions of the molecule are extracellular. The antigenic epitope of the human TAPA-1 is contained within a subregion of the second extracellular domain of the protein. This is the only region in the protein that has not been tightly conserved in mammalian evolution.

Amino Acid Sequence

Genomic organization and chromosomal localization of the TAPA-1 gene.

TAPA-1 is a 26-kDa integral membrane protein expressed on many human cell types. Antibodies against TAPA-1 induce homotypic aggregation of cells and can inhibit their growth. The murine homologue of TAPA-1 was cloned from both cDNA and genomic DNA libraries. A very high level of homology was found between human and mouse TAPA-1. The 5' untranslated region of the TAPA-1 gene resembles housekeeping gene promoters with respect to G + C content and the presence of potential Sp1 binding sites. The chromosomal localization of human and murine TAPA-1 genes was determined by Southern blot experiments using DNA from somatic cell hybrids. The genes were found to be part of a conserved syntenic group in mouse chromosome 7 and the short arm of human chromosome 11. The organization of the TAPA-1 gene and the projection of the exon boundaries on the proposed protein structure are presented.

Amino Acid Sequence

Prevalence of diabetes, hypertension and obesity at different levels of urbanisation in Vanuatu.

OBJECTIVE: To determine the prevalence of non-communicable disease, specifically hypertension, diabetes and obesity, amongst populations at different levels of urbanisation in Vanuatu, and to relate the frequency of these conditions to the modernisation of way of life. DESIGN: A cross-sectional population-based comparative study of indicative cluster samples. SETTING: Republic of Vanuatu (south-west Pacific). A relatively undeveloped malarious island country. PARTICIPANTS: Adult (aged greater than or equal to 20 years) Melanesian ni-Vanuatu of both sexes. An occupation-based (civil servants) urban sample (n = 623) and area-based semi-rural (n = 349) and rural (n = 397) samples were employed. Response rates were 78%-92%. INTERVENTIONS: Cases detected were referred for assessment and treatment by local medical staff. MAIN OUTCOME MEASURES: Body mass index, triceps skinfold thickness, blood pressure, plasma glucose (fasting and 2 hours after 75 g glucose), plasma cholesterol and triglyceride levels. RESULTS: Modernity scores confirmed that the three locations represented different levels of acculturation. Prevalences of non-communicable disease were relatively low compared to other Pacific Island communities and industrialised countries. These conditions were nevertheless more common in the urban sample and least common in the rural sample. Non-communicable disease correlated positively with modernity scores and negatively with physical activity scores. Obesity correlated with blood pressure in the urban sample, and there was indirect evidence (urine sodium concentration) of higher salt intake with modernisation. Mean plasma cholesterol levels were lowest in the rural group. CONCLUSIONS: Prevalences of non-communicable disease are relatively low in Vanuatu, although rural-urban differentials are present, and likely to increase with continued development. The evidence presented is consistent with non-communicable disease being related to the modernisation of way of life; specifically: decreased exercise, obesity, and dietary change. Preventive activities should commence now.

Adult