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Biomedical subjects

I Cohen

Publications and source records attributed to I Cohen.

At least 109 records · Page 6Linked to original sources
PubMed1998

Cytokine production in human mixed leukocyte reactions performed in serum-free media.

The mixed leukocyte reaction (MLR) is an in vitro test commonly performed in a serum-containing medium (SCM), and used to study allorecognition and cellular immunity accompanied by cytokine release. We investigated the possibility of performing the MLR test in serum-free media (SFM) by comparing human leukocyte proliferation and cytokine release in MLRs performed in SFM and SCM. Of the four SFM tested, only Biotarget- was as effective as SCM in supporting leukocyte proliferation and IL-2 secretion. Both phenomena were observed only in allogeneic combinations. The levels of IL-1, IL-6, and TNFalpha in allogeneic MLR combinations in SFM were half those in SCM cultures; the kinetics of their release were the same. With the exception of IL-2, a high degree of spontaneous release of the other three cytokines analyzed was observed in responder cells, in irradiated stimulator cells, and in autologous combinations cultured in both SCM and SFM. It appears that unlike IL-2, the cytokines IL-1, IL-6, and TNFalpha are nonspecifically produced in MLR and cannot serve as sensitive indices of HLA disparity.

Culture Media, Serum-Free↗
PubMed1998

Cerebral cortical hyperactivation in response to mental stress in patients with coronary artery disease.

The central nervous system (CNS) effects of mental stress in patients with coronary artery disease (CAD) are unexplored. The present study used positron emission tomography (PET) to measure brain correlates of mental stress induced by an arithmetic serial subtraction task in CAD and healthy subjects. Mental stress resulted in hyperactivation in CAD patients compared with healthy subjects in several brain areas including the left parietal cortex [angular gyrus/parallel sulcus (area 39)], left anterior cingulate (area 32), right visual association cortex (area 18), left fusiform gyrus, and cerebellum. These same regions were activated within the CAD patient group during mental stress versus control conditions. In the group of healthy subjects, activation was significant only in the left inferior frontal gyrus during mental stress compared with counting control. Decreases in blood flow also were produced by mental stress in CAD versus healthy subjects in right thalamus (lateral dorsal, lateral posterior), right superior frontal gyrus (areas 32, 24, and 10), and right middle temporal gyrus (area 21) (in the region of the auditory association cortex). Of particular interest, a subgroup of CAD patients that developed painless myocardial ischemia during mental stress had hyperactivation in the left hippocampus and inferior parietal lobule (area 40), left middle (area 10) and superior frontal gyrus (area 8), temporal pole, and visual association cortex (area 18), and a concomitant decrease in activation observed in the anterior cingulate bilaterally, right middle and superior frontal gyri, and right visual association cortex (area 18) compared with CAD patients without myocardial ischemia. These findings demonstrate an exaggerated cerebral cortical response and exaggerated asymmetry to mental stress in individuals with CAD.

Adult↗
PubMed1998

Seroprevalence of Babesia equi among horses in Israel using competitive inhibition ELISA and IFA assays.

Sera from 361 horses were tested by indirect immunofluorescence antibody test (IFA) and by competitive inhibition ELISA (cELISA), to detect antibodies to Babesia equi. The concordance between the assays was 95.7%. Application of a cutoff based on a calculated percent inhibition of < 20% gave a total of 22 discrepant results, while only 8 sera negative by the cELISA were found positive by the IFA when a cutoff of > 20% inhibition was used. Approximately one-third of all the horses tested were found serologically positive to B. equi, with more horses testing positive from northern Israel. Among horses raised with access to pasture there was a significant difference in the percentage of seropositive reactors (76.6% in the north and 20.1% in the central region), compared with horses without access to pasture (14.3 and 10.3%, respectively). Nineteen percent of stallions were found to be positive, which was significantly less than the proportions of seropositive mares and geldings: 38 and 42%, respectively. No significant association was found between the mean age of horses and seroreactivity to B. equi.

Animals↗
PubMed1998

Direct versus indirect readout in the interaction of the trp repressor with non-canonical binding sites.

Both direct and indirect readouts are utilized when the trp repressor binds to its operators. Here, we use gel-electrophoretic methods to examine the role played by direct and indirect readouts in the interaction of the repressor with a non-canonical binding site, similar to the mtr operator, and named trpGG. The stability and affinity of the 1:1 complexes of the trp repressor with this non-canonical site are lower than those of the 1:1 complexes formed with either the natural consensus sequence or a consensus sequence found in a selection experiment. We attribute this to the inability of the trpGG target to make the same number of water-mediated hydrogen bonds as canonical trp binding sites. On the other hand, the 2:1 complex of the repressor with trpGG has high stability and affinity, similar to that of the 2:1 complex with a consensus sequence found by a selection experiment. The bend angle induced on the trpGG target by the binding of one repressor molecule is 27 degrees, which is similar to that measured in other 1:1 complexes with the repressor. The angle for the 2:1 complex is significantly larger (43 degrees versus 30 degrees in other 2:1 complexes). We present evidence suggesting that the deleterious effect of the sequence substitution in trpGG is compensated by the increased bend angle in the 2:1 complex. These observations demonstrate that indirect readout may complement for direct readout in determining the nature of the interaction between trp repressor and its binding sites.

Bacterial Proteins↗
PubMed1998

Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction.

BACKGROUND: The incremental prognostic value of stress single photon emission computed tomography (SPECT) for the prediction of cardiac death as an individual end point and the implications for risk stratification are undefined. METHODS AND RESULTS: We identified 5183 consecutive patients who underwent stress/rest SPECT and were followed up for the occurrence of cardiac death or myocardial infarction. Over a mean follow up of 642+/-226 days, 119 cardiac deaths and 158 myocardial infarctions occurred (3.0% cardiac death rate, 2.3% myocardial infarction rate). Patients with normal scans were at low risk (< or =0.5%/y), and rates of both outcomes increased significantly with worsening scan abnormalities. Patients who underwent exercise stress and had mildly abnormal scans had low rates of cardiac death but higher rates of myocardial infarction (0.7%/y versus 2.6%/y; P<.05). After adjustment for prescan information, scan results provided incremental prognostic value toward the prediction of cardiac death. The identification of patients at intermediate risk of nonfatal myocardial infarction and low risk for cardiac death by SPECT may result in significant cost savings when applied to a clinical testing strategy. CONCLUSIONS: Myocardial perfusion SPECT yields incremental prognostic information toward the identification of cardiac death. Patients with mildly abnormal scans after exercise stress are at low risk for cardiac death but intermediate risk for nonfatal myocardial infarction and thus may benefit from a noninvasive strategy and may not require invasive management.

Adenosine↗
PubMed1998

Doppler flow characteristics in patients with pelvic inflammatory disease: responders versus nonresponders to therapy.

PURPOSE: The objective of this retrospective study was to evaluate the role of Doppler flow studies in predicting the response to antibiotic treatment in patients with pelvic inflammatory disease (PID). METHODS: The resistance indices in pelvic masses of 24 patients with clinical diagnoses of PID were analyzed. RESULTS: Twelve patients responded favorably to antibiotic treatment (the conservative treatment group), while the other patients showed no clinical improvement and underwent surgery (surgical treatment group). The mean resistance index in the conservative treatment group was significantly higher (0.60 +/- 0.15) than that in the surgical treatment group (0.52 +/- 0.08; p < 0.05). CONCLUSIONS: In keeping with hyperemia of inflammation, fallopian arterial resistance seems to decrease with the severity of PID.

Adnexa Uteri↗
PubMed1998

Stromal-conditioned medium synergizes with thrombopoietin in stimulating megakaryocytopoiesis.

We previously demonstrated that stromal cells release a soluble factor(s) that enhances thrombopoietin (TPO)-induced megakaryocyte (MK) production. We have now further characterized this enhancing activity of human bone marrow stroma and have also analyzed the role of direct contact of stromal cells with human bone marrow CD34+ cells on MK production. The three- to sixfold stromal-enhancing activity of conditioned media is constitutive and is not influenced by the presence of TPO. The addition of interleukins 3, 6 (IL-3, IL-6), stem cell factor (SCF), and TPO at concentrations found in stroma to a stroma-free system only enhanced by 58% the TPO-stimulated MK production. No influence of heparan sulfates on MK production was observed. In co-cultures of CD34+ cells in direct contact with stromal cells, nonadherent and adherent MK, and proplatelet structures were observed, either in the absence or presence of TPO. Direct contact did not further improve the enhancing activity of stromal cells on MK production induced by TPO. We conclude that the stromal enhancement of MK production is neither accounted for by stromal TPO, IL-3, IL-6, and SCF activities nor modified by physical contact.

Cell Adhesion↗
PubMed1998

Neuregulins and erbB receptors at neuromuscular junctions and at agrin-induced postsynaptic-like apparatus in skeletal muscle.

We demonstrate by immunohistochemistry that at least two isoforms of neuregulin (NRG) are concentrated at neuromuscular junctions in adult rat muscles. One is NRGbeta3, a secreted protein which is bound to basal lamina that occupies the synaptic cleft. The other(s), NRG-a, is in the muscle fibers' plasma membrane. We show further that muscle NRG, including NRG-a, is concentrated at postsynaptic-like apparatus induced to form in the extrajunctional region of the soleus muscle by exposure to neural agrin. The agrin-induced postsynaptic-like apparatus also includes aggregates of the NRG receptors erbB2 and erbB3 as does postsynaptic apparatus at neuromuscular junctions. These findings together with those of others suggest a mechanism by which neural agrin induces the expression of epsilon-AChR subunits in postsynaptic-like apparatus, and they support the hypothesis that agrin has a similar function at neuromuscular junctions.

Agrin↗
PubMed1998

Comparative prognostic value of automatic quantitative analysis versus semiquantitative visual analysis of exercise myocardial perfusion single-photon emission computed tomography.

OBJECTIVES: The purpose of this study was to determine the prognostic value of automatic quantitative analysis in exercise dual-isotope myocardial perfusion single-photon emission computed tomography (SPECT) and to compare the prognostic value of quantitative analysis to semiquantitative visual SPECT analysis. BACKGROUND: Extent, severity and reversibility of exercise myocardial perfusion defects have been shown to correlate with prognosis. However, most studies examining the prognostic value of SPECT in chronic coronary artery disease (CAD) have been based on visual analysis by experts. METHODS: We studied 1,043 consecutive patients with known or suspected CAD who underwent rest Tl-201/exercise Tc-99m sestamibi dual-isotope myocardial perfusion SPECT and were followed up for at least 1 year (mean 20.0+/-3.7 months). After censoring 59 patients with early coronary artery bypass grafting or percutaneous transluminal coronary angioplasty, <60 days after nuclear testing, the final population consisted of 984 patients (36% women, mean age 63+/-12 years). RESULTS: During the follow-up period, 28 hard events (14 cardiac deaths, 14 nonfatal myocardial infarctions) occurred. Patients with higher defect extent (>10%), severity (>150) and reversibility (>5%) by quantitative SPECT defect analysis, as well as those with an abnormal scan (>2 abnormal segments, summed stress score >4 and summed difference score >2) by semiquantitative visual SPECT analysis, had a significantly higher hard event rate compared to patients with a normal scan (p < 0.001). With both visual and quantitative analyses, hard event rates of approximately 1% with normal scans and 5% with abnormal scans (p > 0.05) were observed over the 20-month follow-up period. A Cox proportional hazards regression model showed that chi-square increased similarly with the addition of quantitative defect extent and visual summed stress score variables after considering both clinical and exercise variables (improvement chi-square = 11 for both, p < 0.0007). There were no significant differences in the areas under receiver operating characteristic curves between quantitative and visual analysis (p > 0.70). Linear regression analysis also indicated that quantitative assessments correlated well with visual semiquantitative assessments. CONCLUSIONS: The findings of this study indicate that automatic quantitative analysis of exercise stress myocardial perfusion SPECT is similar to semiquantitative expert visual analysis for prognostic stratification. These findings may be of particular clinical importance in laboratories with less experienced visual interpreters.

Aged↗
PubMed1998

Predictors of medication use, compliance and symptoms of hypotension in a community-based sample of elderly men and women.

OBJECTIVE: To investigate use of prescription and non-prescription drugs, predictors of drug use and symptoms of postprandial and postural hypotension were examined in 765 men and 846 women. METHOD: A questionnaire mailed to 6324 subjects randomly chosen from the electoral roll. RESULTS: Drug use, both prescription and non-prescription, was greater (P < 0.0001) in women (mean 4.1 total drugs, CI 3.9, 4.3) than in men (3.5 drugs, CI 3.3, 3.7); 41% of women and 36% of men used at least four drugs. Total drugs used were significantly greater in women (standardized regression coefficient (b) = 0.101, P < 0.0001), and increased with the number of diagnoses (b = 0.461, P < 0.0001) and taking antidepressants (b = 0.160, P < 0.0001). Use of non-prescription drugs was also greater in women (b = 0.094, P < 0.0001) and in association with arthritis (b = 0.053, P = 0.036) but decreased with age (b = -0.013, P < 0.0001). Potentially important drug interactions occurred in 10% of subjects and included hypoglycaemic agents with b-blockers and asthma with b-blockers. Symptoms of postprandial hypotension, reported in 2.6% of subjects, increased with the number of drugs used (OR 1.17, CI 1.05, 1.31) and with diabetes (OR 2.27, CI 1.05, 4.89). Symptomatic postural hypotension, recorded by 13% of subjects, related significantly to age (OR 1.04, CI 1.02, 1.06), tranquillisers (OR 1.98, CI 1.11, 3.54), antidepressants (OR 2.23, CI 1.30, 3.84) and ACE inhibitors (OR 2.14, CI 1.42, 3.22). CONCLUSION: Reduction in the number and frequency of drug doses and better knowledge about drugs may improve compliance. Observed associations with polypharmacy or hypotension suggest possible approaches to decreasing drug-related illness and limiting the adverse effects of hypotension in the elderly.

Aged↗
PubMed1998

The role of ultrasound in the detection of endometrial pathologies in asymptomatic postmenopausal breast cancer patients with tamoxifen treatment.

Transvaginal ultrasonography is an effective diagnostic procedure, and thus, it can reasonably be used to determine which asymptomatic, postmenopausal breast cancer patient with tamoxifen treatment will require endometrial sampling. Overall, it seems that the contribution of pulsed Doppler flow in the diagnosis of endometrial pathologies in such patients is nonconclusive. It is suggested that sonohysterography is a useful diagnostic tool for the assessment of specific endometrial pathologies, especially of space-occupying lesions in the endometrial cavity, in such patients.

Aftercare↗
PubMed1998

Cooperative organization of bacterial colonies: from genotype to morphotype.

In nature, bacteria must often cope with difficult environmental conditions. To do so they have developed sophisticated cooperative behavior and intricate communication pathways. Utilizing these elements, motile microbial colonies frequently develop complex patterns in response to adverse growth conditions on hard surfaces under conditions of energy limitation. We employ the term morphotype to refer to specific properties of colonial development. The morphologies we discuss include a tip-splitting (T) morphotype, chiral (C) morphotype, and vortex (V) morphotype. A generic modeling approach was developed by combining a detailed study of the cellular behavior and dynamics during colonial development and invoking concepts derived from the study of pattern formation in nonliving systems. Analysis of patterning behavior of the models suggests bacterial processes whereby communication leads to self-organization by using cooperative cellular interactions. New features emerging from the model include various models of cell-cell signaling, such as long-range chemorepulsion, short-range chemoattraction, and, in the case of the V morphotype, rotational chemotaxis. In this regard, pattern formation in microorganisms can be viewed as the result of the exchange of information between the micro-level (the individual cells) and the macro-level (the colony).

Bacteria↗
PubMed1998

Estrogen and progesterone receptors of adenomyosis in postmenopausal breast cancer patients treated with tamoxifen.

Adenomyosis is an ectopic endometrial tissue located in the myometrium. It has been reported to develop at a higher rate among postmenopausal breast cancer patients on tamoxifen (TAM) treatment than in untreated patients. It has also been reported to be stimulated by estrogen. Assessing receptor levels in adenomyotic tissue may indicate the adenomyotic cell's potential to interact with TAM. In the present study the estrogen receptor (ER) and progesterone receptor (PR) were analyzed by an immunohistochemical technique in adenomyotic and the corresponding endometrial tissues of 14 postmenopausal breast cancer patients treated with TAM and in 15 healthy postmenopausal patients who served as controls. All TAM-treated patients had normal postmenopausal serum estradiol levels. Overall the ER and PR contents in adenomyotic tissue (42.9 and 71.4%) and in the endometriotic tissue (64.3 and 78.6%) obtained from the study patients were similar to those obtained from the control group (adenomyosis, ER and PR = 46.7 and 86.7%; endometrium, ER and PR = 40 and 73.3%; p = NS). In the study group, the ER content was lower in the adenomyotic (42.9%) than in the endometriotic tissue (64.3%). No correlation was found between the duration of TAM therapy, the TAM dosage level or the ER or PR content in the adenomyotic or endometrial tissues. The finding of a relatively low ER content in the adenomyotic tissue than in the endometriotic tissue in postmenopausal TAM-treated patients without endogenous estrogens, similar to that observed in healthy premenopausal women, may be attributed to the estrogen-like effect of TAM.

Aged↗
PubMed1998

Estrogen and progesterone receptors in benign ovarian tumors of menopausal breast cancer patients treated with tamoxifen.

In order to assess possible ovarian cell potential for interaction with tamoxifen, thus demonstrating possible effects of this agent on the development of ovarian pathologies through growth stimulation and cell proliferation, we measured estrogen receptors (ER) and progesterone receptors (PR) by immunohistochemical method in 16 benign ovarian tumors removed from 11 postmenopausal breast cancer patients treated with tamoxifen (study group). The results were compared with those measured in 7 similar ovarian tumors obtained from 5 similar patients without tamoxifen treatment (control group I), and in 9 similar tumors removed from 9 age-matched postmenopausal women (control group II). There were no significant differences with regard to ER or PR expression between the study group and control group I and II (ER = 18.75, 0.0 and 11%, respectively; PR = 43.75, 28.5 and 44%, respectively; p = NS). There were also no significant statistical differences between the three groups when subdividing the ovarian pathologies according to different histological types. From the results obtained in this study, it seems that tamoxifen probably does not have any direct influence on the ovaries of menopausal breast cancer patients.

Aged↗
PubMed1998

Different coexisting gynecological and endometrial pathologies in postmenopausal breast cancer patients treated with tamoxifen.

Tamoxifen administration to postmenopausal women has been described as being associated with various endometrial and other gynecological pathologies. However, different coexisting gynecological pathologies in such patients have not yet been described. In the present study, we assessed the histopathological conditions diagnosed in endometrium, myometrium, and ovaries of 28 postmenopausal breast cancer patients who were treated with tamoxifen (study group) and compared the findings to those obtained from 14 similar patients without tamoxifen treatment (control group I) and from 28 age-matched healthy postmenopausal controls (control group II). All specimens were removed by total abdominal hysterectomy and bilateral salpingo-oophorectomy for various indications. The overall incidence of two or more different coexisting gynecological pathologies was significantly higher among the study group (92.9%) than in control group I or in control group II (42.9 and 50%, respectively; p = 0. 0001). There was no significant statistical difference between the control groups. Overall endometrial (and endometrial-like) origin of pathological conditions was significantly more common in the study group (92.6%) than in control group I (50%; p = 0.00072) and control group II (32.1%; p = 0.0000), while there was no significant difference between the latter two groups. These findings suggest that there might be an association between postmenopausal tamoxifen exposure and the development of such different coexisting or specific single gynecological pathologies originating from the endometrium.

Aged↗