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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 523 records · Page 29Linked to original sources
PubMed1989

Attachment of tumor cells to endothelial monolayers: detection of surface molecules involved in cell-cell binding.

Trypsinization of P815 mastocytoma cells interferes with their ability to bind to endothelial monolayers in vitro, suggesting the involvement of proteins in cell-cell binding. Binding is also dependent upon divalent cations. Incubation of tumor cells with tunicamycin, which blocks protein glycosylation, or the monosaccharide N-acetyl-D-glucosamine could also inhibit binding. In addition, antibodies prepared against whole P815 cells had the ability to interfere with tumor cell binding. The protein fragments released from P815 cells by trypsin interfered with the binding of fresh P815 cells to endothelium. Moreover, those fragments as well as CHAPS extracts of tumor cell membranes were able to neutralize the inhibitory effect of an anti-P815 antibody on tumor cell-endothelial cell binding. These observations, taken together, strongly suggest the presence of adhesion molecules on the tumor cell. The anti-P815 antibody preparation could also inhibit endothelial binding of an unrelated tumor. Ehrlich ascites (EA). In addition, membrane preparations of EA could neutralize the antibody's effect on intact P815, and membrane preparations of P815 could neutralize the antibody's effect on EA. These observations suggest that there are common epitopes on these tumor cells and raise the possibility that a variety of tumors may share common mechanisms for attachment to endothelium. This, in turn, raises the possibility that monospecific antibodies against such epitopes might be useful agents for interfering with metastasis in vivo.

Animals↗
PubMed1989

Intracellular mechanisms of lymphoid cell activation.

Activation of lymphocytes for proliferation is associated with the appearance of an intracellular factor (ADR) that can induce DNA synthesis in isolated quiescent nuclei. ADR plays a role in the sequence of intracellular events leading to activation for IL-2-mediated proliferation. Because of the nature of the defining assay, the locus of ADR action appears to be near the terminal end of the transduction pathway. Interestingly, although lymphocytes from aged individuals respond poorly to proliferative stimuli, they appear to produce normal to above-normal levels of ADR. In contrast, their nuclei are only poorly responsive to stimulation by ADR. Preparations rich in ADR activity have proteolytic activity as well. In addition, aprotinin, as well as a variety of other protease inhibitors, suppresses ADR-induced DNA synthesis in a dose-dependent manner. ADR activity can be removed from active extracts by absorption with aprotinin-conjugated agarose beads, and can be removed from the beads by elution at pH 5.0. This latter suggests that ADR itself is a protease. However, its endogenous substrate is not yet known. We have also detected an inhibitor of ADR activity in the cytoplasm of resting lymphocytes. This is a heat-stable protein of approximately 60,000 Da. In addition to suppressing the interaction of ADR with quiescent nuclei, the inhibitor can suppress DNA synthetic activity of replicative nuclei isolated from mitogen-activated lymphocytes. Interestingly, these preparations had little or no activity on replicative nuclei derived from several neoplastic cell lines. The resistance of tumor cell nuclei to spontaneously occurring cytoplasmic inhibitory factors such as the one described here may provide one explanation for the loss of growth control in neoplastic cells.

Animals↗
PubMed1989

Degenerative arthritis of the carpus associated with congenital hypoplastic thumb.

The case history of a young man with bilteral congenital hypoplastic thumbs and early degenerative arthritis involving the base of the thumb and scaphotrapeziotrapezoid joints is reported. To our knowledge this association has not been previously made. Limited intercarpal arthrodesis and/or trapezium arthroplasty may be required at a relatively early age in patients with thumb dysplasia. We believe the hypoplastic thenar musculature may lead to instability and excessive shear stresses on the radial side of the carpus, causing the early arthritic changes.

Adolescent↗
PubMed1989

Aging and defective lymphoid cell activation.

Activation of lymphocytes for proliferation is a crucial process in the immune response. Age-related deficiencies in this cellular response strongly correlate with deficiencies in the immune system response, with concomitant increase in disease severity and mortality. Defects associated with the transmission of the initial activation signal and with IL-2 production contribute to the depressed response, but defects in the IL-2 response mechanism also play important roles. A major factor in this area is the inability of the nuclei of these cells to respond to the intracellular factor ADR, which plays a crucial role in the initiation of DNA replication. These cells produce normal levels of ADR; thus, either the nuclei cannot bind ADR in a productive manner or the defect lies beyond the point of ADR binding, perhaps in one of the other proteins of the initiation complex. An interesting contrast to the age-related failure of nuclei to respond to ADR is the failure of neoplastic nuclei to respond to the ADR inhibitor. This inhibitor, found in the cytoplasm of quiescent cells, suppresses both the activation of quiescent nuclei by ADR and the ongoing DNA synthesis in isolated nuclei from activated cells. Nuclei from spontaneous proliferating cell lines were not affected by this inhibitor, which may be an important factor in the uncontrolled growth seen in neoplastic cells. The investigation of ADR has given hints that perhaps two of the fundamental questions in biology, namely why some cells don't proliferate and why some others won't stop proliferating, may be two sides of the same coin.

Aging↗
PubMed1989

Follicle size by ultrasound versus cervical mucus quality: normal and abnormal patterns in spontaneous cycles.

Ultrasound (US) has been demonstrated to be the method of choice for diagnosing luteinized unruptured follicle syndrome and to be a valuable adjuvant in the assessment of luteal phase defect. In this prospective study, the use of US with postcoital testing (PCT) is evaluated. Fifty control infertility patients were examined with serial US for follicle dynamics in conjunction with PCT. Standard curves for follicle dynamics versus cervical mucus quality (Insler score) were calculated. Eighteen patients referred for abnormal mucus underwent similar evaluation. Their follicle dynamics versus mucus quality were compared with those of the controls. The findings were: (1) there is a predictable relationship between follicle size and mucus quality, (2) the majority of patients with abnormal mucus have normal follicular dynamics, and (3) a minority of patients with abnormal mucus have either a narrow mucus window or abnormal follicular dynamics. In addition, US was found to be cost-effective in the overall fertility evaluation.

Cervix Mucus↗
PubMed1989

Debunking myths about self-quitting. Evidence from 10 prospective studies of persons who attempt to quit smoking by themselves.

This article examines data from 10 longterm prospective studies (N greater than 5,000) in relation to key issues about the self-quitting of smoking, especially those discussed by Schachter. When a single attempt to quit was evaluated, self-quitters' success rates were no better than those reported for formal treatment programs. Light smokers (20 or less cigarettes per day) were 2.2 times more likely to quit than heavy smokers. The cyclical nature of quitting was also examined. There was a moderate rate (mdn = 2.7%) of long-term quitting initiated after the early months (expected quitting window) of these studies, but also a high rate (mdn = 24%) of relapsing for persons abstinent for six months. The number of previous unsuccessful quit attempts was unrelated to success in quitting. Finally, there were few occasional smokers (slips) among successful long-term quitters. We argue that quitting smoking is a dynamic process, not a discrete event.

Follow-Up Studies↗
PubMed1989

Production of monoclonal antibodies toward bovine interferons-alpha suitable for immunopurification.

Five murine hybridoma clones, producing monoclonal antibodies (MAbs) to bovine interferon-alpha (BoIFN-alpha) were established. One of these, F12, secreted MAbs giving high titers, in ELISA tests, neutralizing both BoIFN-alpha, -alpha C, and BoIFN-alpha D activities, belonging to the mouse IgG1 class, and having a binding affinity constant of 10(8) M-1. F12 MAbs were used for immunoaffinity purification of BoIFN-alpha, and recombinant BoIFN-alpha C from Escherichia coli extracts was purified to homogeneity in SDS-PAGE analysis and to a specific activity of 2 X 10(8) U/mg with 90% recovery of activity.

Animals↗
PubMed1989

Potentiation by mild hypothermia of ventricular conduction disturbances and reentrant arrhythmias induced by bupivacaine in dogs.

High concentrations of bupivacaine and profound hypothermia individually cause intraventricular conduction disturbances and reentrant arrhythmias. The effects of the combination of relatively low concentrations of bupivacaine and mild hypothermia are unknown and are the subject of this study. Three groups (n = 10-12) of dogs anesthetized with thiopental-chloralose were treated as follows: group 1, bupivacaine + hypothermia; group 2, bupivacaine alone; group 3, hypothermia alone. Bupivacaine was administered as a 4 mg/kg iv bolus followed by an iv infusion of 0.1 mg.kg-1.min-1. Hypothermia, i.e., a 4 degrees C reduction in core temperature, was produced by cooling the blood with an extracorporeal circuit. The peripheral ECG was recorded to determine the duration of QRS complexes and the QT interval. Conduction time and effective refractory period (ERP) of ventricular contractile tissue were measured with right ventricular endocavitary electrodes. Measurements were made with the heart paced at 180 beats/min and without pacing. In group 1 dogs, bupivacaine (plasma level, 2.8 +/- 0.3 microgram/ml) initially caused a prolongation of conduction time and QRS duration, which were further lengthened (approximately doubled) by a temperature decrease of 4 degrees C from baseline. The QT interval and ERP also were increased but to a lesser degree. In dogs in which the effects were most pronounced, rhythm disorders, such as wave burst arrhythmias (most common), premature systoles, ventricular tachycardia, and even ventricular fibrillation, occurred either spontaneously or during pacing. Bupivacaine alone (group 2) increased QRS duration and conduction time significantly, whereas hypothermia alone (Group 3) did not cause changes in any conduction variables. In neither group were dysrhythmias observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Demographic and clinical features predictive of recovery in acute mania.

Discrepancies exist in previous reports regarding clinical and demographic features associated with recovery in acute mania. The authors studied 44 hospitalized patients with bipolar affective disorder, manic type. They report a significant association between more depressive symptomatology and perhaps younger age of illness onset, and poor immediate treatment response. They also found the total amount of psychopathology at admission, as measured by the Brief Psychiatric Rating Scale and Manic State Rating Scale, and the degree of psychosis to be unrelated to immediate outcome. The authors suggest that the not recovered manic subgroup has a distinct illness or a variant of bipolar disorder with poor prognosis that warrants further and separate investigation.

Acute Disease↗
PubMed1989

Vascular cholinesterases and choline uptake in isolated rat forebrain microvessels: a possible link.

The two parameters of the active [methyl-3H]choline uptake into isolated rat forebrain microvessels, Km and Vmax, were determined for 1-, 3-, 10-, and 24-month-old Charles River male rats and compared with the activities of the enzymes choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) in these microvessels over the same time course. The value of Km remained constant over the entire period, but that of Vmax increased from 8.5 +/- 1.0 to 80.6 +/- 16.4 nmol g-1 (mean +/- SEM) over the first 3 months of life. Over the same period, the increase in ChAT activity, from an initial value of 7.1 +/- 1.6 to 10.2 +/- 0.3 nmol g-1 min-1, was not proportional to that of choline uptake. Levels of BuChE activity (0.9-1.3 mumol g-1 min-1) were almost unchanged throughout the entire 24-month period, but those of AChE showed a steady and significant increase from 1 to 24 months, remaining relatively high at senescence (4.7 mumol g-1 min-1), when choline uptake had decreased to one-third of its optimal value. Selective inhibition of AChE with 1,5-bis(4-allyldimethylammonium-phenyl)pentan-3-one dibromide (0.5 microM) in unruptured capillaries from 3-month-old rats resulted in a decrease in Vmax of choline uptake from approximately 81 to 59 nmol g-1 min-1 or with 9-amino-1,2,3,4-tetrahydroacridine (10 microM) in capillaries from 2-month-old rats from approximately 30 to 15 nmol g-1 min-1. Selective inhibition of BuChE with tetraisopropyl pyrophosphoramide (100 microM) resulted in an increase in Vmax from approximately 81 to 96 nmol g-1 min-1. It is possible that the two vascular enzyme systems are coupled to a hypothetical endothelial choline transporter, but with an action opposite to each other.

Aging↗
PubMed1989

Semliki Forest virus E2 envelope epitopes induce a nonneutralizing humoral response which protects mice against lethal challenge.

Along the 422 amino acids of the Semliki Forest virus (SFV) E2 envelope glycoprotein, we identified 13 peptide cassettes (ranging in size from 15 to 25 amino acids and designated A through N) that contain hydrophilic sequences flanked by amino acid sequences conserved in the E2 envelopes of the alphavirus family. Six peptide blocks containing either a single cassette or two to three contiguous cassettes (A, BC, DE, FG, HIK, and LMN) were produced in Escherichia coli as recombinant proteins fused to the N terminus of beta-galactosidase. All of the SFV E2 recombinant polypeptides except A-beta-galactosidase were recognized on Western blots (immunoblots) by anti-SFV polyclonal antisera. In addition, these five recombinant proteins induced in mice antibodies that interacted specifically with SFV E2 protein on Western blots as well as with the intact virions in an enzyme-linked immunosorbent assay. The six hybrid proteins were used to vaccinate mice and were tested for the ability to confer resistance against lethal doses of SFV. Peptides BC and HIK, located at amino acid positions 114 to 149 and 216 to 288, respectively, of E2, protected partially (40 to 60%) against SFV challenge. A third peptide, LMN, located between amino acid positions 289 and 352, rendered mice totally resistant to an SFV challenge of 250 50% lethal doses. The partially protective effects of the BC and HIK cassettes and the high efficacy of the LMN cassette were consistently demonstrated, independent of the adjuvant (complete Freund or alum), immunization protocol, and strain of mice used. None of the antisera raised against any given cassette could neutralize the virus in an in vitro tissue culture assay or in a plaque reduction neutralization test. Nevertheless, passive transfer experiments demonstrated that in the case of LMN, the protective effect was mainly of a humoral nature.

Amino Acid Sequence↗
PubMed1989

Recombinant human epidermal growth factor precursor is a glycosylated membrane protein with biological activity.

NIH 3T3 cells were transfected with cDNA corresponding to human kidney prepro-epidermal growth factor (preproEGF) under control of the inducible mouse metallothionein promoter. The synthesis of recombinant human EGF precursor by these cells has provided us with a model system for analysis of the structure and activity of this precursor. In transfected cells, the precursor was present as an intrinsic 170-kilodalton membrane protein as well as a soluble protein in the extracellular medium; both forms were N glycosylated. Glycosylation of the EGF precursor was determined by (i) the direct incorporation of [3H]mannose and [3H]glucosamine, (ii) metabolic labeling in the presence or absence of glycosylation inhibitors, (iii) enzymatic cleavage of the precursor by N-glycanase or endoglycosidase II, and (iv) lectin chromatography. Recombinant human preproEGF was purified by affinity chromatography, using wheat germ lectin and antibodies to human EGF. The intact precursor was biologically active. Purified preparations of preproEGF (i) competed with 125I-labeled EGF for binding to the EGF receptor in intact fibroblast cells, (ii) activated the intrinsic tyrosine kinase activity of the EGF receptor in membrane preparations, and (iii) sustained the growth of a mouse keratinocyte cell line that is dependent on EGF for growth. These results suggest that proteolytic processing of the precursor may not be essential for its biological function.

Binding, Competitive↗
PubMed1989

Nasal versus temporal preretinal vasoproliferation in retinopathy of prematurity.

Nasal preretinal neovascularisations have been observed to develop at least two weeks earlier than those on the temporal side in more than a third of premature babies with retinopathy of prematurity (ROP) stage 3, weighing between 690 and 1030 g. All these babies were assigned for cryotherapy. This interesting observation is discussed in relation to retinal vascular development and the pathogenesis of ROP.

Humans↗
PubMed1989

Mechanics and neuropeptide responses of feline pylorus and gastric muscle in vitro.

Mechanical properties and neuropeptide responses were compared for feline pyloric and gastric muscle under isometric conditions in vitro. Total tension in antral circular muscle (0.699 +/- 0.003 kg/cm2) was less than in corpus circular (1.597 +/- 0.007 kg/cm2) or longitudinal muscle from the lesser and greater curvatures (1.256 +/- 0.009 and 1.253 +/- 0.007 kg/cm2, n greater than or equal to 55, P less than 0.05). The components of tension at optimal length were similar for all gastric muscles (P greater than 0.1). The pylorus maintained less total tension (0.335 +/- 0.003 kg/cm2) and a greater component of resting tension (75.6%) than gastric muscle (P less than 0.01). Substance P, cholecystokinin-8 (CCK-8), and neurotensin varied in potency and efficacy in circular muscle of the antrum, corpus, and inferior portion of the pyloric ring. Longitudinal muscle and the superior portion of pylorus responded poorly if at all to neuropeptides. Substance P- but not CCK-8- or neurotensin-induced contractions of gastric muscle were reduced by tetrodotoxin (TTX) and atropine (P less than 0.05). Substance P-induced pyloric contractions were TTX sensitive (P less than 0.05) but were unaffected by atropine. We concluded that 1) length-tension properties of gastric muscle are similar and distinct from the pylorus and that 2) neuropeptide efficacy varies regionally within the feline stomach and within the pylorus.

Acetylcholine↗