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Biomedical subjects

B Gonen

Publications and source records attributed to B Gonen.

At least 19 recordsLinked to original sources
PubMed1996

Behavior of F-response and determination of actively involved motoneurons.

Fifteen nerves were examined in 10 healthy subjects, using a collision technique with 2 stimulation pulses of different intensity on the same point. The F-waves which occurred after the antidromic activation of the motor neuron cells by the first supramaximal pulse were blocked on their return pathway by the collision with the depolarization induced by the second pulse. The progressive decrement of the voltage of the second stimulus allowed, the transmission of the recurrent discharge along motor fibers with a lower depolarization threshold. The amplitude and the persistence of the F-waves increased (p < 0.05 and p < 0.001 respectively), while their latency decreased (p < 0.01) concurrent with the liberation of additional motor neurons with a lower threshold of depolarization. These findings suggest that the F-wave may be elicited in motoneuron of different depolarization threshold but primarily in larger and faster nerve fibers, with a lower threshold of depolarization.

Adolescent↗
PubMed1992

In vivo tumorigenicity and in vitro sensitivity to tumor-necrosis-factor alpha mediated killing of c-Ha-ras-transformed cells.

Cellular subclones of high and low tumorigenicity obtained from a mouse c-Ha-ras-transformed clone, were examined for their sensitivity to tumor-necrosis-factor (TNF)-mediated cytotoxicity. Cells of the highly tumorigenic subclones showed a significantly enhanced resistance to the cytotoxic effect of TNF plus cyclohexamide (CHI) as compared to cells of the low-tumorigenic subclones. The enhanced resistance to TNF+CHI was not due to a lower expression of TNF receptors on the cells. The c-Ha-ras-transfected cells were transformed and maintained in culture only (C cells). In vivo passage of cells of the initially low-tumorigenic c-Ha-ras subclones through the mouse significantly enhanced the tumorigenic potential of these CTC cells (culture/tumor/culture). In correlation with their enhanced tumorigenicity, the CTC cells were highly resistant to TNF-mediated cytotoxicity as compared to C cells of the same subclone. Furthermore, the involvement of TNF in determining the tumorigenic phenotype of the c-Ha-ras-transformed cells was demonstrated in a more direct manner. Cells of a c-Ha-ras-transformed low-tumorigenic, highly TNF-sensitive subclone were selected by repeated cycles of in vitro exposure to TNF alpha. As a result, a stable, highly TNF-resistant population of cells emerged. These TNF-resistant cells caused more tumors in mice as compared to their original TNF-sensitive cells. These results show that the resistance to the cytotoxic effect of TNF plus cyclohexamide may be involved, at least partially, in the tumorigenic potential of c-Ha-ras-transformed cells and suggest a possible role for TNF in the enhancement of the tumorigenic potential of these cells in mice.

3T3 Cells↗
PubMed1992

Phenotypic properties of 3T3 cells transformed in vitro with polyoma virus and passaged once in syngeneic animals.

Cloned BALB/c 3T3 cells transformed in vitro with polyoma virus (PyV) acquired a higher tumorigenicity phenotype after a single in vivo passage. Some of the in vivo passaged cells (CTC cells) exhibited also a higher metastatic phenotype than cells from the same clones that were maintained only in culture (C cells). A phenotypic comparison between CTC and C cells was performed. It was found that most CTC lines exhibited a higher binding to laminin compared to their clonal C cell ancestors. Some CTC cells were less sensitive to the cytotoxic effects of TNF-alpha than the corresponding C cells. CTC cells originating from tumors which appeared after a long latency period (late tumors) tended to express Fc gamma RII while CTC cells originating from tumors which appeared after a short latency period (early tumors) as well as the corresponding C cells tended not to express Fc gamma RII. The expression of a membrane epitope recognized by a monoclonal antibody expressing specificity towards PyV transformed cells, was down-regulated on late tumor cells compared to early tumor cells. Transfection of cloned PyV-transformed BALB/c 3T3 cells with the beta 1Fc gamma RII gene augmented the tumorigenicity and metastatic phenotype of the transfectants compared to control transfectants.

3T3 Cells↗
PubMed1992

Possibilities of interference with the immune system of tumor bearers by non-lymphoid Fc gamma RII expressing tumor cells.

The ectopic expression of Fc gamma RII by PyV transformed 3T3 cells derived from tumors of long latency has been established. It was suggested that this expression is one of several changes conferring upon the cells an increased capacity for survival. We found that in one case cells expressing a very high level of Fc gamma RII had also a very high metastatic phenotype as compared to FcR negative cells. Direct evidence that Fc gamma RIIbl functions as a progression factor was provided by transfection experiments. The transfected gene conferred an increased malignancy and invasive phenotype upon PyV or c-Ha-ras transformed cells. In the present study we tested the possibility that Fc gamma RII expressing tumor cells could interfere with the immune system. The following subjects were investigated: 1) The ability of Fc gamma R on the tumor cells to bind the ligand and/or release IBF. 2) The effect of a local accumulation of ligand and/or IBF (assumed to take place in situ in the tumor) on Fc gamma RII expressing T cells. It was found that both tumor-derived receptor positive and beta l transfected PyV transformed cells were capable of binding aggregated mouse IgG. The binding of bivalent ligand was followed by an increase in membrane Fc gamma RII expression. Also both types of cells were capable of releasing IBF. We then tested the possibility that a local accumulation of IgG within the tumor could effect Fc gamma R expressing T cells. It was found that aggregated mouse IgG (as well as IgGl) could stimulate the proliferation of the T cell hybridoma (T2D4) and other Fc gamma RII expressing T cells. We also found that the expression of beta Fc gamma RII specific mRNA peaked at the logarithmic phase of T2D4 cultures, in parallel with their maximal potential to release IBF. Several pathways for interference with the immune system are suggested.

3T3 Cells↗
PubMed1992

Diagnostic value of computer analysis of multipeaked EMG spikes.

Computer analysis of absolute number of peaks per second and the number of peaks in the multipeaked spikes/sec was carried out in the EMG interference recordings of 5 healthy, 6 myopathic and 8 neuropathic subjects. The purpose of the study was to detect diagnostically different patterns. A spike was considered multipeaked if it had 6 or more peaks. The amplitude of elimination (baseline) was examined at 1: 5, 1: 10 and 1: 15 of the average amplitude per second. Both the number of peaks and the number of peaks in multipeaked spikes in the neuropathic and myopathic muscles showed statistically significant differences when compared to healthy muscles. This technique could give an indication for the differential diagnosis of myopathic, neuropathic or healthy state of the muscle.

Arm↗
PubMed1991

Fourier series analysis of the electrophysiological pattern of fatigue in healthy human beings, after curare administration.

Real time computer analysis of the electrophysiological development of muscular fatigue after small doses of d-tubocurarine (TC), has been examined in anesthetized human beings. As compared to a decrease of frequency in the control measurements, previous studies have shown an increase of the frequency of spikes after TC administration. The present experiments were carried out on the biceps brachii of 8 healthy human volunteers maintained in isometric contraction against a constant counter load until complete fatigue occurred. The Fourier spectrum analysis showed a statistically significant shift to lower frequencies before, and a milder statistically non significant shift after TC. These results may indicate that under mild curarization the early phase of muscular contraction requires a higher number of large motor units and thus, at a later stage of the contraction the pool of available large motor units becomes smaller. This conclusion supports the hypothesis that mild curarization causes a state of initial muscular fatigue.

Action Potentials↗
PubMed1990

Manometry and electromyography of the pharyngeal muscles in patients with dysphagia.

Simultaneous recording of the electromyographic activity of the pharyngeal muscles and the intraluminal pressure in the upper sphincter zone was performed routinely in patients with swallowing problems for the first time, to our knowledge. This technique was found to be very useful for the localization of the "site of lesion." The procedure is safe, easy to master, and causes minimal inconvenience. It can reveal, in the most direct way, whether the disturbance is in the hypopharyngeal musculature (represented by the inferior constrictor muscle), in the cricopharyngeal muscle (spasm or lack of relaxation), or in the synchronization between them. Simultaneous recording of intraluminal pressure adds valuable information about the mechanical events associated with electromyographic activity. It was found that in pathologic cases there is quite often no correlation between the electrical and mechanical events. Thus, simultaneous recording of both electrical and mechanical events is essential for the understanding of the pathophysiology of disturbances of deglutition.

Adult↗
PubMed1990

Electromyography of the inferior constrictor and cricopharyngeal muscles during swallowing.

Electromyography (EMG) of the inferior pharyngeal constrictor (IC) and the cricopharyngeal (CP) muscle was recorded in 18 patients with swallowing and/or aspiration problems who were candidates for cricopharyngeal myotomy. The EMG recordings were compared to those of 13 "normal" subjects who did not suffer from such problems. Differences in EMG activity between the control group and the patient group were considered with respect to the clinical symptoms in the patient group. Recording of EMG in the CP and IC muscles is relatively safe, useful, and easily mastered. The technique may provide important information regarding the function of some of the muscles involved in deglutition.

Adult↗
PubMed1990

Comparison of the electrophysiological pattern of fatigue between athletes required to perform explosive and endurance sports.

The electrophysiological behavior of an isometric contraction sustained to fatigue, was examined in 6 long distance runners and 9 athletes involved in explosive (burst) sports, by on line computer analysis of the electrical activity of vastus medialis, rectus femoris and vastus lateralis. The experiments were carried out with a counterload of 50% of the maximal strength of the muscle. The duration of spike increased and the frequency decreased in the 3 examined muscles, in both types of sport. In the burst sports the changes of value of both parameters were statistically significant in the 3 muscles. In endurance sports the variations of duration were not significant and the changes of frequency were statistically significant only in the vastus lateralis. These results could be explained by the gradual activation of motor units of more strikingly different sizes in burst sports. Thus it may be speculated that prolonged training in burst sports may result in the automatic mobilization of higher number of small motor units, for the initiation of contraction while in endurance sports the onset of contraction is more gradual and carried out by large motor units.

Adolescent↗
PubMed1988

Some immunological properties of high and low tumorigenic cellular variants of c-H-ras transformed 3T3 cells.

NIH 3T3 cells transformed in vitro with the c-H-ras oncogene were subcloned. The resulting subclones were assayed for in vivo tumorigenicity in nude and in immunocompetent mice. The response of two high tumorigenic and two low tumorigenic clones to mediators of natural immunity was analyzed. The clones did not differ in sensitivity to NK cell-mediated lysis. However, compared to low tumorigenic clones, the high tumorigenic ones had a down-regulated expression of a membrane determinant recognized by a certain monoclonal naturally occurring antibody. The determinants recognized by other monoclonal naturally occurring antibodies available in the laboratory were equally expressed on the high and low tumorigenic clones. The high tumorigenic cells showed an increased resistance to cytotoxicity mediated by lymphotoxin. These results suggest that naturally occurring antibodies and lymphotoxin may participate in controlling the tumorigenicity of transformed cells. The high tumorigenic clones but not the low tumorigenic ones contained a novel 3.5-kb ras mRNA.

Animals↗
PubMed1987

Low density lipoprotein (LDL) inhibits histamine release from human mast cells.

We examined the effect of low density lipoprotein (LDL) on histamine release from purified human lung mast cells. LDL inhibited anti-IgE- induced histamine release in a dose-dependent manner, with 100 micrograms/ml LDL-protein inhibiting histamine release by 53 +/- 8% (mean +/- SEM); half-maximal inhibition occurred at 40-80 micrograms/ml. LDL also inhibited calcium ionophore A23187-induced histamine release in a dose-dependent manner, with 1 mg/ml of LDL inhibiting histamine release by 83 +/- 9%; half maximal inhibition occurred at 220-280 micrograms/ml. Inhibition by LDL was time-dependent: half-maximal inhibition of anti-IgE- induced histamine release by LDL occurred at 30-50 minutes of incubation. The inhibitory effect of LDL was independent of buffer calcium concentrations (0-5 mM) or temperature (0-37 degrees C). These data are consistent with a newly defined immunoregulatory role for LDL.

Calcimycin↗
PubMed1987

Enzyme linked immunosorbent assay for the measurement of nonenzymatically glucosylated proteins in serum and in tissues.

We have developed an enzyme linked immunosorbent assay (ELISA) for glucosylated proteins. The polyclonal antiserum was prepared against reduced glucosylated lipoproteins and was specific for the glucose-lysine bond. The antiserum recognized, in a dose-dependent manner, all reduced glucosylated proteins tested, including albumin, fibrinogen, low density lipoprotein, high density lipoprotein and hemoglobin, yet had no affinity for native proteins or to glucosylated but nonreduced proteins. The sensitivity of the assay was in the order of 1-5 pmol glucosylated lysine/ml and half maximal displacement occurred at 8-24 pmol glucosylated lysine/ml. The inter- and intraassay variables were 10.8% and 13.5%, respectively. Serum proteins from diabetic patients (n = 30) contained 84 +/- 6 picomoles of glucosylated lysine/mg protein, compared to 28 +/- 3 in controls (n = 20), and the concentration of glycosylated proteins correlated with fasting blood glucose (r = 0.56, p less than 0.02), but not with glucosylated hemoglobin levels (r = 0.29, p greater than 0.1). Proteins from diabetic glomeruli and aortae similarly contained more glucosylated lysine residues than controls.

Aorta↗
PubMed1987

Very low density lipoproteins (VLDL) trigger the release of histamine from human basophils.

Circulating basophils are well established sources of the granule-associated mediator, histamine. The physiological control, however, of histamine release from human basophils is poorly understood. Because histamine may play a role in the transendothelial transport of various compounds, including very low density lipoprotein (VLDL) and its hydrolysis products, we investigated the possibility that VLDL regulates mediator release from basophils. The incubation of VLDL (at physiological concentrations) with basophils (isolated as mixed leukocyte preparations) resulted in a significant release of histamine. Histamine release was dependent on VLDL concentration (half-maximal stimulation occurring at VLDL-protein concentration of 15-20 micrograms/ml), length of incubation (half-maximal release at 5-12 min), temperature (37 degrees C optimum) and required calcium (concentration 0.5-2.0 mM). Furthermore, VLDL-induced histamine release was inhibited by three different mediator-release inhibitors: dimaprit, dibutyryl cAMP and nordihydroguaiaretic acid. Incubation of basophils with LDL or HDL under the same experimental conditions did not result in significant histamine release from basophils. The histamine-secretory response of basophils obtained from different donors varied considerably. Basophils isolated from 28 donors and challenged with 100 micrograms/ml VLDL released 23 +/- 5% of their cellular histamine (mean +/- S.E.; with a range of 0-94%). Desensitization of VLDL-induced histamine release could be accomplished by preincubation of basophils with either VLDL or anti-IgE but not with N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Through the secretion of histamine, a potent vasoactive mediator (and also possibly through granule-associated glycosaminoglycans, stimulants of the enzyme lipoprotein lipase), this novel effect of VLDL may be part of a physiological loop for the regulation of VLDL hydrolysis and lipid transport. This effect of VLDL may also have deleterious consequences, because of the atherogenic properties of histamine.

Basophils↗
PubMed1987

Immunogenicity of malondialdehyde-modified low density lipoproteins. Studies with monoclonal antibodies.

Malondialdehyde (MDA)-modified low density lipoprotein (LDL) can stimulate the accumulation of cholesteryl esters in cultured macrophages through its interaction with specific scavenger receptors. It has been speculated that such interaction occurs in vivo thus contributing to the formation of foam cells within atherosclerotic lesions. This report describes the development of new tools in the form of a specific assay for MDA-LDL to investigate this hypothesis. We have immunized BALB/c mice with malondialdehyde mouse low density lipoproteins and antibodies against malondialdehyde human low density lipoproteins were generated. Monoclonal antibodies were produced using hybridoma techniques and one particular clone (EB 7-3) was expanded for further studies. The immunoreactivity of several antigens was tested using antibody EB 7-3 in an enzyme-linked immunosorbent assay (ELISA). In a typical assay malondialdehyde human LDL (with at least 40% of lysines modified) was coated (2 micrograms/ml, 100 microliter) in 96-well microtiter plates. Antibody plus one of several antigens were then added and the interaction between the antibody and coated antigen was measured using alkaline phosphatase-conjugated affinity purified goat anti-mouse immunoglobulin. The binding of antibody EB 7-3 to wells coated with malondialdehyde-LDL was competitively inhibited by malondialdehyde-LDL added in solution, with half maximal inhibition occurring at 150 +/- 80 ng/ml. In addition, the ability of malondialdehyde-LDL to inhibit this interaction was proportional to the degree of modification: the more lysines were modified the more did malondialdehyde-LDL inhibit the binding of antibody EB 7-3 to coated malondialdehyde-LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1986

Marker and function analysis of natural killer and alloreactive T cells during early stages of dimethylbenzanthracene carcinogenesis. The immunity system during the precancer period.

The effect of the chemical carcinogen dimethylbenzanthracene (DMBA) on cellular immunity was studied at a 6-mg dose which induces adenocarcinomas and adenoacanthomas in more than 70% of BalB/c mice within 1 year after administration. DMBA caused a significant reduction of splenic natural killer (NK) activity and responsiveness to alloantigens in mixed lymphocyte reactions (MLR). These activities decreased soon after the carcinogen treatment and remained suppressed during the entire tumor induction period. There was a linear correlation between the reduction in NK activity and a selective decrease in the number of asialo GM1 positive cells in the spleen. However, cell sorting experiments using the flow cytometer have shown that the lytic activity per cell of asialo GM-1 positive cells in untreated mice and in DMBA-treated ones was similar. There was no correlation between the suppressed response of the T cells in MLR and the percentage of T cell subpopulations residing in the spleen of the DMBA-treated mice. The decrease in the number of NK cells and the reduced MLR activity in the spleen occurred simultaneously with a decrease in the potential of bone marrow precursor cells to reconstitute NK and MLR activity in the spleen of lethally irradiated mice. These results indicate that the carcinogen DMBA effects the immune system at various levels and either eliminates or inactivates precursor cells as well as mature lymphoid cells.

9,10-Dimethyl-1,2-benzanthracene↗