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Biomedical subjects

I Cohen

Publications and source records attributed to I Cohen.

At least 343 records · Page 19Linked to original sources
PubMed1983

HLA-D "BG" in Israel. A Japanese related allele population and family study.

An homozygous typing cell for a local HLA-D determinant"BG", defined by family study, is described. HLA-D "BG" recognizes a specificity identical to the Japanese HLA-DHO (Dw12). Two families and 102 randomly selected healthy Israeli individuals were typed for the HLA-D "BG" determinant. HLA-D "BG" showed segregation as a single determinant within families. The gene frequency for this allele was 0.045, compared to the frequency of 0.148 for DHO in Japanese. In the Israeli population "BG" is in strong association with HLA-Bw52 (joint occurrence = 7.80%) and DR2 (joint occurrence = 8.80%), resembling the data reported foar DHO (Dw12) in Japan. The frequency of this allele may partially account for the low frequency of HLA-Dw2 in the Israeli population.

Alleles↗
PubMed1983

Peroneal tendon dislocations: a review of the literature.

Acute anterior dislocation of the peroneal tendons from behind the peroneal groove is uncommon but not rare. The injury must be evaluated carefully to determine whether conservative treatment will suffice or surgical intervention is required. Choice of a surgical procedure depends on the fibular groove, the nature of the retinaculum, and the amount of damage to the area.

Adult↗
PubMed1983

Hematin: unique effects of hemostasis.

Hematin is clinically useful in the treatment of acute intermittent porphyria. Recently, hematin-induced coagulopathy has been reported, and a patient we treated bled during hematin therapy. On 3 separate occasions, infusions of hematin (4 mg/kg) induced thrombocytopenia, prolongation of the prothrombin time, partial thromboplastin time. Reptilase time, and apparent decreases in fibrinogen and increases in fibrin(ogen) degradation products (FDP). However, fibrinogen assayed by heat precipitation was unchanged, the protamine paracoagulation test was negative, there was no red blood cell fragmentation, and plasminogen and antithrombin III remained normal, excluding the presence of disseminated intravascular coagulation. Furthermore, premedication with heparin, 5000 U i.v., failed to prevent the lengthening of the Reptilase time and exacerbated the thrombocytopenia. In vitro studies revealed that hematin, 0.1 mg/ml, aggregated platelets and induced the release of 14C-serotonin and adenosine triphosphate (ATP). Hematin also aggregated washed or gel-filtered platelets but had no effect on formalin-fixed platelets. Aggregation was inhibited by aspirin (0.12 mg/ml), adenosine triphosphate, and apyrase, suggesting that hematin aggregated platelets by inducing adenosine diphosphate (ADP) release. Hematin (0.07 mg/ml) progressively inactivated thrombin and 0.1 mg/ml prolonged the Reptilase time. Thus, hematin is unique in that it both induces platelet aggregation and inhibits coagulation.

Adult↗
PubMed1982

The interaction of extracellular H+, Na+, Ca2+ and Sr2+ on the decay of miniature end-plate currents.

We suggested previously that increases in the extracellular [Ca2+] or [Mg2+] lengthen miniature end-plate currents (m.e.p.c.s.) because the divalent cations decrease the negative surface potential on the end-plate, and thereby increase the voltage drop within the membrane. The increased voltage drop would lengthen the open time of the end-plate channels. Increased extracellular [H+] is also known to lengthen m.e.p.c.s.15; perhaps also acting by changing the surface potential. There has been dispute about the observations and their interpretation. Reducing the [Na+]0 at pH = 7.4 from 120 to 12 mM decreased the half-time of m.e.p.c. decay by nearly a factor of two. When the same changes in [Na+]0 were performed at pH = 5.2, no change in m.e.p.c. decay was detected. This suggests that the H+ titrates the negative surface charges, so they no longer can be affected by [Na+]0. The data do not fit the hypothesis that lifetime is determined by the presence of permeant ions in the channel 4,16. At pH = 7.4 replacing the 2.5 mM CaCl2 by SrCl2 decreased the m.e.p.c. decay rate by 60%17. This effect is not seen at pH = 5.2. We suggest that at pH = 7.4, Sr2+ binds to fixed negative charges on the end-plate and thereby slows the decay. H+ titrates the fixed charges and decreases the Sr2+ effect. In low [Na+] saline, raising [Ca2+]0 shortened m.e.p.c. decay--an effect exactly opposite to that expected from the change in surface potential. Under these conditions, increasing the [Ca2+] decreases the m.e.p.c. decay rate by some other mechanism; this second effect of Ca2+ on m.e.p.c. decay may account for some of the different results reported.

Animals↗
PubMed1982

Ultrastructure of clots during isometric contraction.

We explored the retraction or contraction of platelet-fibrin clots under isometric conditions. In the presence of micromolar calcium clots of normal platelet-rich plasma developed tension at an initial rate of 0.1 to 0.2 g/min per cm2 (initial cross-sectional area). Electron microscopy of clots fixed after attaining a force of 1.6 g/cm2 revealed platelets with elongated bodies and pseudopods in close apposition to fibrin strands which were oriented in cablelike fashion in the direction of tension. The development of tension could not be explained simply on the basis of platelet-platelet association and interaction alone. First, factor XIII-dependent cross-linking of fibrin fibers was critical to normal isometric contraction. Second, tension decreased linearly, rather than exponentially, when the platelet count in the platelet-fibrin clot was decreased, suggesting that platelets must be interacting with another component (i.e. fibrin). Thrombasthenic platelets, deficient in fibrinogen receptors, failed to develop tension or to align fibrin strands or pseudopods in the clot. Platelet-fibrin clots treated with vincristine to disassemble microtubules or cytochalasin B to disrupt microfilaments failed to develop tension and relaxed if these agents were added after tension had developed. Relaxation under these conditions, however, was not associated with loss of orientation of fibrin strands. Our findings suggest that platelet-fibrin interaction in clots under isometric conditions leads to orientation of fibrin strands and platelets in the direction of force generation. Tension develops as platelets simultaneously attach to and spread along fibrin strands, and contract. The contraction draws some fibrin into platelet-fibrin clumps and aligns other strands in the long axis of tension. The achievement and maintenance of maximum tension appears to depend on the development of platelet-fibrin attachments and extension of platelet bodies and long pseudopods containing bundles of microfilaments and microtubules along the oriented fibrin fibers.

Blood Platelets↗
PubMed1982

HLA-D locus in Israel. Characterization of 14 local HTC's and a population study.

Fourteen homozygous typing cells identified in Israel are described. Of these typing cells two were of Ashkenazi and 11 of non-Ashkenazi origin, while the remaining HTC was from an Arab donor. Ten of the 14 HTC's characterized in this manner were offspring of consanguineous marriages; all of them were non-Ashkenari. Nine HTC's express specificities previously recognized in Caucasians, 4 HTC's represent new specificities (J1-J4), and one typing cell was found to be analogous to the Japanese Dw12 (DHO) specificity. The distribution of HLA-D specificities in 120 randomly selected Israelis representing the two main Jewish subpopulations, Ashkenazim and non-Ashkenazim, was studied with the locally defined HTC's. HLA-Dw5 and Dw10 were found to be significantly increased while Dw2 and Dw6 were significantly decreased in Israelis as compared to Caucasians.

Chromosome Mapping↗
PubMed1982

HLA-D typing in multiple sclerosis: Israelis tested with European homozygous typing cells.

The association of A3, B7, Dw2 and DR2 histocompatibility (HLA) markers with multiple sclerosis (MS) is well established among Northern Europeans and Caucasoids in the United States. We showed previously that A3 and B7 were not increased among Israelis with MS, and in a preliminary study Dw2 as well. An association of A3 and B7 is also lacking in Italians, Jordanian and Japanese MS patients. In Black American MS patients, the B7 frequency is slightly increased but Dw2 is still significantly associated with MS. For the HLA-DR antigen series DR2 is shown to have a stronger association to MS than A3 and B7. Conceivably, this antigen could be associated with MS even in populations where an association with A3 or B7 is lacking. Therefore, a study of HLA-A, B, C, DR and D antigens was carried out in Israel. No significant excess or deficiency of HLA antigens was found in MS. Possible explanations for these results are as follows: (1) the relevant HLA-D alleles in the Jewish population were not detected by the homozygous typing cells (HTCs) used, since they were derived primarily from European sources; (2) in contrast to the Caucasoid populations the genetic factor predisposing for MS is not associated with HLA alleles in the Israeli population; (3) MS is an heterogeneous disease and in Israelis, an environmental factor is sufficient to cause the disease.

Europe↗
PubMed1982

Histocompatibility (HLA) antigens and multiple sclerosis in Israelis.

The association of A3, B7 and Dw2 histocompatibility (HLA) markers with multiple sclerosis (MS) is well established among North Europeans and Whites in the United States, but is apparently not universal. We previously showed that the incidence of A3, B7 and Dw2 was not higher among Israelis with MS. An association of A3 and B7 was also lacking in Italian, Jordanian and Japanese groups with MS. Recently, the HLA-DR antigen DR2 was shown to have a stronger association with MS than do A3 and B7. Conceivably, DR2 could be associated with MS even in populations where an association with A3 or B7 is lacking. Therefore, a study of DR antigens was carried out in 45 carefully defined Israeli MS patients and in matched control subjects. No significant association between MS and DR antigens was found. We conclude that the association between HLA antigens and MS is specific only to certain populations or particular regions. The implications of this observation on the role played by HLA antigens in the etiopathogenesis of MS is discussed.

HLA Antigens↗
PubMed1981

The dependence of the maximum rate of rise of the action potential upstroke on membrane properties.

The maximum rate of rise of the action potential (Vmax) is often used to study the maximum sodium conductance (GNa) of excitable membranes, by assuming that Vmax is proportional to GNa. However, the real relation between Vmax and GNa is uncertain. We use simple analytical descriptions of the membrane currents to investigate this relation. If (1) the sodium conductance is greater than the non-sodium conductance of the membrane, (2) the sodium current is activated extremely quickly, and (3) the sodium current is inactivated extremely slowly, then Vmax will indeed be proportional to GNa. However, if conditions (1) or (3) are not satisfied, the Vmax-GNa relation will be non-proportional, such that a certain fractional change of GNa produces a larger fractional change of Vmax. If condition (2) is not satisfied the Vmax-GNa relation is distorted in the opposite direction, such that a certain fractional change of GNa produces a smaller fractional change of Vmax. Measurements of Vmax are usually performed in preparations where voltage clamping cannot be used to study GNa directly. However, voltage clamping is necessary to verify that conditions (1)-(3) are satisfied. The results of studies using Vmax alone as a measure of GNa should be assessed with caution.

Action Potentials↗
PubMed1981

The timing of channel opening during miniature end-plate currents.

Many chemical transmitters act by opening channels with exponentially distributed life-times. We present a way to analyze a synaptic current in terms of its component channels. We can estimate the numbers and times of channel opening within the synaptic current. This approach is used to study miniature end-plate currents (m.e.p.c.s) at the frog neuromuscular junction. The results support the idea that some transmitter rebinds after dissociation from post-synaptic receptors, and suggest that the time of channel closing is related to the time at which acetylcholine leaves the receptor.

Acetylcholine↗
PubMed1981

Ca2+-dependent cross-linking processes in human platelets.

When platelet cytoplasmic Ca2+ is increased by the ionophore A23187 in the presence of the protease inhibitor leupeptin, there is the coincident appearance of a cross-linked polymer and the partial disappearance of monomeric protein and glycoprotein units. In the absence of leupeptin only 30% of the polymer was formed. The disappearance of monomeric protein bands, as detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis, is prevented by histamine, which as a pseudodonor amine is a known inhibitor of transglutaminase-catalyzed cross-linking [14C]Histamine, at a tracer concentration, is incorporated into the polymer as well as into myosin, glycoproteins IIb and III, actin and tropomyosin. The loss of monomeric protein bands is mostly due to their conversion into polymers. Control measurements show that leupeptin effectively inhibited platelet Ca2+-dependent proteases. The cross-linking processes bringing about the observed increase in polymer formation are thus the result of a Ca2+-dependent platelet transglutaminase activity. The latter is located in the platelet cytosol and has been identified as platelet factor XIII on the basis of its specific cross-linking of fibrin. Platelet factor XIII, upon activation, may function physiologically to couple membrane proteins to cytoplasmic structural proteins. Thus, a new concept is proposed for the stabilization of platelet membranes and platelets as they form the hemostatic plug.

Blood Platelets↗
PubMed1981

Suppressor mononuclear cells in giant lymph node hyperplasia and thymoma.

The existence of suppressor mononuclear cells were demonstrated in two lymphoproliferative disorders: giant lymph node hyperplasia and thymona. The three patients tested also showed cell-mediated immunodeficiency as expressed in the low number of T cells, negative graft versus host reactions and negative skin tests; the one patient tested with phytohemagglutinin (PHA) and concavalin A (Con A) showed a low response. Suppressor activity was tested with a new experimental model, the local xenogeneic graft versus host reaction. It is proposed that this model be used for testing suppressor activities in other human disorders as well.

Adolescent↗
PubMed1981

The effect of water deficit on body temperature during rugby.

Sweat losses, water deficits and changes in rectal temperature were measured in 13 first-league players during a rugby match. Changes in plasma volume, serum electrolyte and blood glucose levels were also determined. Rectal temperatures were markedly elevated after the match. Both temperatures reached levels which are known to be associated with an impairment of physical, mental and psychological function, and could have caused a deterioration in performance during the second half of the match. Body temperatures were high enough to have predisposed to aggressive behaviour. Increases in rectal temperature were related to water deficit. The small volumes of fluid ingested by the players just before and during the match suggest that they are unaware of the importance of preventing dehydration. Recommendations are made to reduce the risk of hyperthermia. Glucose and electrolyte supplementation is not required just before and during rugby.

Adult↗
PubMed1981

Genetics of insulin dependent diabetes mellitus in Israel: population and family study.

The association between insulin dependent diabetes mellitus (IDDM) and the HLA system was studied in two groups of Jewish patients: 50 Ashkenazim and 42 non-Ashkenazim. The pattern of association of HLA-A and B locus antigens was somewhat different from that observed in European Caucasian patients. HLA-B8 had a higher frequency; B15 and Cw3 were rare in the population studied and were less frequent in IDDM patients than in controls. On the other hand, the frequency of A26, B18, and Bw38 was increased in Ashkenazi patients, but not in non-Ashkenazim, who in turn showed an increase for Bw51. Although the association between IDDM and HLA-A and B locus antigens shows a marked variability in different populations, the association with HLA-DR3 and DR4 is constant feature. There was a typical excess of DR3/DR4 heterozygotes in both patient groups. This heterozygote type carries the highest relative risk, followed by DR4/DR4 homozygotes. These data can well be interpreted by a model of two different HLA-linked susceptibility genes, one associated with DR3 and the other one with DR4, that interact so that different genotypes are associated with different levels of penetrance. This model received further support from studies in 15 multiple case families where there is an excess of affected sib pairs sharing two DR antigens.

Adolescent↗