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Biomedical subjects

Y Ben-David

Publications and source records attributed to Y Ben-David.

At least 73 records · Page 4Linked to original sources

Brainstem auditory evoked potential with increased stimulus rate in minor head trauma.

Fifteen Minor Head Trauma patients were investigated by Brainstem Auditory Evoked Potentials at 10/s and 55/s stimulus rate. The results were compared with those of the same patients at a second examination, two months later, as well as with a matched normal control group. Increasing the stimulus rate in MHT patients caused a significant but reversible delay in the central conduction time. No significant difference was found regarding the interpeak latency differences at a 10/s stimulus rate. The present study suggests that the primary lesion in MHT is ischaemic, affecting synaptic efficiency, and not axonal damage. These findings may be informative on the as yet obscure pathophysiological mechanism of minor head trauma.

Audiometry, Evoked Response↗

Identification and mapping of a common proviral integration site Fli-1 in erythroleukemia cells induced by Friend murine leukemia virus.

Friend murine leukemia virus (F-MuLV) induces erythroleukemia when inoculated into newborn BALB/c or NIH/Swiss mice. We have molecularly cloned F-MuLV host cell DNA junction fragments from an erythroleukemia cell line induced by F-MuLV to identify cellular genes involved in the leukemogenic process. One particular proviral integration site, Fli-1, is rearranged in 75% (9/12) of independently isolated erythroleukemia cell lines derived from either BALB/c or NIH/Swiss mice inoculated at birth with F-MuLV. Other hematopoietic neoplasms induced by F-MuLV, including myeloid (granulocytic) and lymphoid tumors, did not show rearrangements of the Fli-1 locus. Similarly, none of 35 erythroleukemia cell lines induced by the Friend virus complexes (FV-A and FV-P) was rearranged at the Fli-1 locus. In contrast, no rearrangements were detected at the Sfpi-1 locus, a preferred site of integration in either FV-P- or FV-A-induced leukemias. Using recombinant inbred mice, the Fli-1 locus was situated on mouse chromosome 9 close to the cellular protooncogene c-ets-1. DNA and RNA analysis suggests, however, that Fli-1 is different from ets-1. Thus, Fli-1 appears to define a distinct locus specifically involved in the induction of erythroid leukemias by F-MuLV.

Animals↗

Insertional inactivation of the p53 gene during friend leukemia: a new strategy for identifying tumor suppressor genes.

Rearrangements within the p53 gene are observed in a high proportion of independent erythroleukemic cell lines derived from the spleens of mice infected with Friend leukemia virus. The majority of cells with at least one rearranged p53 allele do not express detectable levels of p53 protein. Here, we show that in 4 out of 19 newly established erythroleukemic cell lines induced by infecting DBA mice with either the anemia (FV-A) or polycythemia (FV-P)-inducing strains of Friend virus, the p53 gene is rearranged as a result of integration of spleen focus-forming virus (SFFV). Integration of SFFV within the p53 gene resulted in inactivation of gene expression as determined by Western blot analysis. The sites of SFFV integration in the p53 gene were found, by Southern blot analysis and the polymerase chain reaction, to be localized in a 1-kbp region between introns 7 and 9. In addition, loss of the normal p53 allele was observed in three of the erythroleukemic cell lines that carried a rearranged p53 gene. Insertion of SFFV in these cell lines resulted in either the appearance of aberrant p53 transcripts or the complete lack of p53 expression. The results presented in this paper demonstrate that retroviral insertions can not only contribute to neoplastic transformation by activating dominant oncogenes but also by inactivating genes that normally function in a negative way to control cell growth. Thus, it may be possible to identify additional genes of this class by characterizing chromosomal sequences that are adjacent to common sites of retroviral integration in tumors.

Alleles↗

Early prediction of left ventricular function in streptokinase-treated acute myocardial infarction.

We administered 750,000 units of intravenous streptokinase to 121 consecutive patients experiencing their first acute myocardial infarction within 4 h of pain onset. The following information was collected: hours between pain onset and streptokinase administration (TS), hours of pain after streptokinase administration (DP), initial and peak creatine phosphokinase levels (ICK and PCK), time to peak creatine phosphokinase, time to electrocardiographic ST segment resolution. Six days after the infarction, catheterization was performed to calculate ejection fraction, infarct-related regional ejection fraction, and dysfunction index. Data was analyzed using stepwise multiple regression. In patients experiencing anterior infarctions, the following equation was obtained predicting the ejection fraction (EF) with a correlation coefficient of 0.86: EF = 69 - 0.0050(PCK) - 3.7(TS) - 1.8(DP). In anterior infarctions the infarct-related ejection fraction and dysfunction index were similarly predictable. We were slightly less accurate in forecasting the outcome of inferior infarctions. The outcome of intravenous streptokinase therapy can be predicted early in the evolution of acute myocardial infarction using routinely available information.

Adult↗

Clonal analysis of radiation leukemia virus-induced leukemic and preleukemic murine cells.

Clonality of radiation leukemia virus (RadLV)-induced thymic lymphomas was determined by detection of rearrangements in the genetic locus coding for the beta chain of the T-cell receptor (T beta). Unique T beta rearrangements were detected in four of six lymphomas. Two of the T beta-rearranged thymic lymphomas and two in which such a rearrangement was not detected had a biallelic deletion of C beta 1. With an anti-RadLV monoclonal antibody it was found that 1-2 days after virus inoculation more than one-third of the cells in the thymus were infected by the virus. The frequency of virus-positive cells gradually declined and persisted at 1-2% until the appearance of a clonal lymphoma at which time virtually all the cells in the thymus were virus positive. Transfer of thymocytes from a single, preleukemic mouse 21 days post-virus inoculation into several adoptive recipients resulted in donor-type thymic lymphomas in the majority of the mice. T beta rearrangement analysis revealed that these lymphomas were clonal and derived from different potentially leukemic (preleukemic) cells in the thymus of the donor mouse. Eleven of 15 lymphomas had a biallelic deletion of C beta 1. These results suggest that clonal, RadLV-induced thymomas are selected from an oligoclonal, RadLV-infected preleukemic T-cell population.

Alleles↗

Multistage Friend erythroleukemia: independent origin of tumor clones with normal or rearranged p53 cellular oncogenes.

The erythroleukemia induced by Friend virus complex in adult mice is a multistage malignancy characterized by the emergence, late in the disease, of tumorigenic cell clones. We have previously shown that a significant proportion of these clones have unique rearrangements in their cellular p53 oncogene. The clonal relationships among Friend tumor cells isolated in the late stages of Friend erythroleukemia were analyzed by examining the unique integration site of Friend murine leukemia virus and the unique rearrangement in their cellular p53 oncogene. The majority of clones isolated from individual mice infected with Friend virus were clonally related as judged by the site of Friend murine leukemia virus integration. However, Southern gel analysis of DNA from individual Friend cell clones indicated that all of the clones with a normal p53 gene from the same mice were clonally related, but were unrelated to the Friend cell lines with a rearranged p53 gene. These results suggest that Friend tumor cells with rearrangements in their p53 gene arise as the result of a unique transformation event, rather than by progression from already existing tumor cells with a normal p53 gene. They also suggest that such rearrangements in the p53 gene confer a strong selective advantage to these cells in vivo.

Animals↗

Early treatment of acute myocardial infarction with intravenous streptokinase. A high-risk syndrome.

Fifty-one successive patients treated with intravenous streptokinase 1.7 +/- 0.8 (mean +/- SD) hours after onset of symptoms of acute myocardial infarction were evaluated during a three-month posthospital follow-up period. Coronary angiography was performed four to nine days after the initial hospital admission. Twenty-eight patients had a second late angiogram. Forty-one patients had successful reperfusion but only 25% of all patients were without significant clinical cardiovascular manifestations during this period. Postmyocardial infarction angina pectoris occurred in 21 patients, an abnormal stress test result was present in 28 patients, eight patients developed congestive heart failure, and five patients had reinfarction. An intervention with percutaneous transluminal coronary angioplasty or coronary artery bypass graft was performed in 15 (37%) of 41 reperfused patients. A significantly higher intervention rate was present in patients treated with streptokinase within one hour following the onset of symptoms. Early reocclusion (within three months of the infarct) was noted in patients with 60% or more residual stenosis in their infarct-related coronary artery. These patients also had a significantly greater incidence of angina pectoris. Our findings indicate that early thrombolytic therapy of acute myocardial infarction preserves myocardium, and since the infarct-related artery is patent, but narrowed, the jeopardized area is responsible for a high-risk syndrome with an increased likelihood of ischemic symptoms. An early aggressive approach may be indicated, especially for patients with greater than 60% residual stenosis in their infarct-related coronary artery.

Adult↗

Importance of early initiation of intravenous streptokinase therapy for acute myocardial infarction.

The importance of timing of intravenous streptokinase (SK) administration in patients with acute myocardial infarction (AMI) was evaluated. Intravenous SK, 750,000 U, was administered within 4 hours of the onset of ischemic chest pain to 72 consecutive patients having their first AMI. Six days later, cardiac catheterization was performed to calculate global ejection fraction (EF), and computer-derived infarct-related regional EF and dysfunction index were also determined; electrocardiograms were recorded, from which QRS scores could be calculated to estimate infarct size. Of 19 patients who had an anterior AMI, 12 (63%) who received intravenous SK within 2 hours after onset of pain sustained only minimal damage in terms of global EF, infarct-related EF, dysfunction index and QRS score. All 10 patients who received SK 2 to 4 hours after pain onset had large infarcts (p less than 0.001). Of the former group, 11 of 12 patients (91%) whose pain was relieved within 1.5 hours of intravenous SK administration (presumably due to successful reperfusion) had a good outcome, whereas all 7 whose pain lasted longer did poorly (p less than 0.001). Furthermore, among patients with anterior AMI, 11 of 14 (79%) whose pain was relieved within 3.5 hours of onset had small infarcts, compared with none of the 12 patients whose pain lasted longer (p less than 0.0001). In inferior AMI, the critical time between onset of pain and initiation of intravenous SK was 1.5 hours (p less than 0.05). The timing of initiation of thrombolytic therapy and the total pain duration are critical in determining outcome in AMI, and time intervals vary depending on infarct localization.

Aged↗

Noninvasive recordings of cochlear evoked potentials in Meniere's disease.

Noninvasive meatal electrocochleography simultaneously recorded with brain stem auditory evoked potentials were performed on 24 adult patients with unilateral Meniere's disease. Data from the affected ear were compared with those of the nonaffected ear and with those of ten healthy normally hearing adults. The most striking finding was the significant deviation from the norm of the nonaffected ears' action potential duration. The combination of simultaneously recorded surface meatal electrocochleography and brain stem auditory evoked potentials complement the diagnostic battery of Meniere's disease in ruling out retrocochlear involvement, indicating cochlear involvement of the affected ear, and revealing subclinical changes in the contralateral ears.

Adult↗

Bradycardia and hypotension following reperfusion with streptokinase (Bezold-Jarisch reflex): a sign of coronary thrombolysis and myocardial salvage.

Acute myocardial infarction, particularly of the inferior wall, is frequently associated with bradycardia and hypotension. This study reports the occurrence of transient bradycardia hypotension (TBH) (Bezold-Jarisch reflex) following thrombolytic therapy with intravenous streptokinase. Of the 52 patients, 42 had successful reperfusion, and 12 of the latter developed reflex TBH. The Bezold-Jarisch reflex occurred in 10 of 24 patients with inferior wall acute myocardial infarction and in 2 of 28 patients with anterior wall infarction (p less than 0.05). The reflex was associated with significantly more non-Q wave infarctions (p less than 0.05) and also with reduction of left ventricular damage, as evidenced by a lower QRS score (4 +/- 3.8 vs 8.9 +/- 5.6, p less than 0.01) and a higher ejection fraction (61 +/- 13% vs 49 +/- 16%, p less than 0.05). Patients with inferior wall acute myocardial infarction were divided into those with TBH (10 patients) and those without TBH (14 patients). TBH was associated with a significantly higher infarct-related regional ejection fraction (60 +/- 19% vs 35 +/- 18%, p less than 0.05). The results of this study confirm previous findings that reperfusion of the inferoposterior myocardium is capable of stimulating reflex TBH. Furthermore, TBH is associated with patency of infarct-related coronary arteries and myocardial salvage.

Adult↗

Auditory brain-stem evoked potentials in patients undergoing dialysis.

Auditory brain-stem evoked potentials (ABEPs) and pure-tone audiograms were obtained for 38 patients with renal failure, undergoing dialysis, before and after a dialysis session, and for 40 healthy normal subjects. Blood chemistry was also evaluated for each patient before and after dialysis. ABEP abnormality (using 10/sec click rate) was observed for 24% of the patients, rising to 44% when 55/sec measures were included. Abnormalities included prolongations of peak latencies for both click rates, and prolongation of interpeak latency differences. Pre-dialysis calcium was significantly different between patients with or without ABEP abnormality. In addition to this chronic effect on ABEPs, an acute effect of the dialysis session was found. Blood chemistry data, ABEP latencies and I-III interpeak latency differences were significantly different before, as compared to after dialysis. The acute effect of dialysis on blood calcium levels correlated with its effect on latencies of peaks III and V at 10/sec click rate, and on peaks I and V latency at 55/sec. These results may indicate the types of dysfunction revealed by increased stimulus rate measures.

Auditory Perception↗

Immunity and suppression in radiation- and radiation leukemia virus (RadLV)-induced leukemogenesis.

Adult C57BL/6 (B6) mice exposed to fractionated irradiation or inoculated with a highly leukemogenic RadLV (A-RadLV) develop high incidence of lymphatic leukemias after a latency of 3-5 months. Inoculation of a low leukemogenic RadLV variant (D-RadLV) does not result in lymphoma development unless the animals receive a single, sublethal dose of irradiation. Whereas virus-induced primary lymphomas produce virus, express gp70 and are all immunogenic, those induced by X-rays are devoid of virus expression and are not immunogenic. A-RadLV inoculation into B6 mice is associated with early induction of virus specific, cyclophosphamide sensitive suppressor T cells which are capable of abrogating a potential antitumor immune responsiveness. D-RadLV, on the other hand, induces reactive T lymphocytes that arrest leukemogenesis unless their function is impaired by irradiation. In (B6 X BALB/c)F1 mice both A-RadLV and D-RadLV leukemogenesis depend on sublethal irradiation of the host, and both induce reactive T cells. These results suggest that (a) RadLV and X-ray induced leukemogeneses involve different etiologies. (b) Different leukemogenic treatments evoke different host responses early in latency which can either sustain or interfere with lymphoma progression.

Animals↗

A comparison of auditory brain stem evoked potentials in hyperlipidemics and normolipemic subjects.

Twenty-five hyperlipidemic, neurologically and audiologically asymptomatic patients were compared to 20 normolipemic control subjects regarding different interpeak latency differences (IPLD) of auditory brain stem evoked potentials (ABEP). ABEP were recorded in response to click stimuli presented at a rate of 10/sec and 55/sec. The net effect of increasing stimulus rate (ISR) on IPLD of ABEP was significantly greater in the hyperlipidemic patients for IPLD (V-I) and IPLD (III-I). ISR of ABEP indicates a trend of subclinical impairments of brain stem function in hyperlipidemic patients, probably due to ischemia accelerated by their condition.

Acoustic Stimulation↗

The hyperacute phase of right ventricular infarction.

In summary, the hyperacute phase of RV infarction presents three possible patterns on the surface ECG (Fig. 3): the typical repolarization picture of hyperacute myocardial infarction, with slope elevation of the ST segment and tall T waves; rounded elevation of the ST segment, where the typical changes are "damped" by negative or posterolaterally directed, LV repolarizing forces; and ST elevation concave upward in the right chest leads, where anteriorly directed, underlying left ventricular ST segment and T wave vectors enhance the hyperacute picture.

Acute Disease↗

Suppressor and reactive lymphocytes in radiation leukemia virus (RadLV)-induced leukemogenesis.

Suppressor cells capable of enhancing tumor growth in vivo and of abrogating a potential anti-tumor immunity in vitro are generated in C57BL/6 mice inoculated with the high-leukemogenic A-RadLV. Mice inoculated with low-leukemogenic D-RadLV do not develop suppressor cells but contain anti-tumor reactive lymphocytes that can inhibit in vivo tumor growth. Cyclophosphamide (CyF) treatment of mice inoculated with A-RadLV hampered suppressor cell function and rendered the animals' lymphocytes responsive to A-RadLV induced tumor cells in vitro. Administration of CyF also reduced leukemia incidence in mice inoculated with A-RadLV, but had no effect on leukemia induction by D-RadLV in irradiated mice. It is suggested that the high leukemogenic activity of A-RadLV depends on the virus' ability to recruit CyF-sensitive suppressor cells early in latency and that tumor progression in mice inoculated with D-RadLV is arrested due to the host immune response.

Animals↗