Corynebacterium pseudodiphtheriticum pulmonary infection in AIDS patients.
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Biomedical subjects
Publications and source records attributed to Y Cohen.
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The precursor of photosystem I (PSI) subunit II (pre-subunit II) synthesized in vitro, was found to bind to the holo-PSI complex, both within the thylakoids and outside, after detergent extraction of PSI from the membranes. Chloroplast stromal fraction added to the purified PSI complexes, containing the labeled pre-subunit II, induced the processing of the precursor to the mature form. This implies that processing can occur within the isolated complex, after the integration of the precursor. The results presented suggest that certain aspects of biogenesis of membranal protein complexes can be studied in detergent-extracted purified complexes.
The biogenesis and assembly of subunit II of photosystem I (PSI) (psaD gene product) were studied and characterized. The precursor and the mature form were produced in vitro and incubated with intact plastids or isolated thylakoids. Following import of the precursor into isolated plastids, mostly the mature form of subunit II was found in the thylakoids. However, when the processing activity was inhibited only the precursor form was present in the membranes. The precursor was processed by a stromal peptidase and processing could occur before or after insertion of the precursor into the thylakoids. Following insertion into isolated thylakoids, both the precursor and the mature form of subunit II were confined to the PSI complex. Insertion of the mature form of subunit II was much less efficient than that of the precursor. Kinetic studies showed that the precursor was inserted into the membrane. Only at a later stage, the mature form began to accumulate. These results suggest that in vivo the precursor of subunit II is inserted and embedded in the thylakoids, as part of the PSI complex. Only later, it is processed to the mature form through the action of a stromal peptidase.
A 39-year-old male developed primary brain lymphoma 33 years after receiving scalp irradiation for tinea capitis. This is the first reported association between cranial irradiation during childhood and subsequent development of primary brain lymphoma.
Breast hemangioma in female infants is a rare benign lesion, prone to spontaneous regression. But when the lesion regresses there is a risk of breast atrophy if the breast bud is included in or very close to the hemangioma. A trial of corticosteroid therapy could be proposed to prevent this risk, but one must be sure that the breast bud is included in or very close to the hemangioma before treatment. We studied 4 children with breast hemangioma to evaluate the ability of MR Imaging in the diagnosis of breast bud inclusion. 0.5 Tesla axial Spin Echo T2-weighted images (TR = 2000 ms; TE = 120 ms) clearly depicted interface between high signal appearance of hemangioma and hypo-intensity of the breast bud: in our four patients we were able to determine whether or not the hemangioma involved the breast bud. Our preliminary study seems to demonstrate that MR imaging is a valuable imaging technique to determine which patients could be eligible for a trial of corticosteroid therapy.
A case of liposarcoma of the perineum and scrotum, which presented as a huge haematoma and was left in place for three years prior to excision, is presented. The patient was treated by wide excision of the tumour, orchiopexy to the inguinal region and radiotherapy. To date, 30 months following surgery, the patient is completely asymptomatic and no tumour recurrence is evident either on physical and rectal examinations or on chest X-rays, ultrasonography and abdominal and pelvic computerized tomography.
In 1987 a retrospective analysis was performed of 116 patients with carcinoma of the prostate localized to the pelvis who were treated by radiotherapy at the Northern Israel Oncology Center during the period between 1977 and 1982. It was shown that definitive external beam irradiation is an effective, simple, and easy treatment modality for localized prostatic cancer.
This is a retrospective analysis of 147 evaluable patients, with histologically proven renal cell carcinoma, who were referred to our center between 1977 through 1988. All patients with disease limited to the kidney underwent nephrectomy. Post-operative megavoltage irradiation, with a median dose of 46 Gy, was given to 56 patients, using parallel opposing portals, or multiple field technique. Five and 10 year actuarial survivals in irradiated patients (Rt+) were 50 and 44%, respectively, and in non-irradiated patients (Rt-) 40 and 32%, respectively. The disease recurred locally in a total of 19 patients; 16 had tumor bed recurrence and three had scar recurrence. Local recurrence by stage was as follows: T2 N0M0: RT+ 0/17, RT- 2/28; T3 N0M0: RT+ 4/37 (10%), RT- 11/30 (37%) (p less than 0.05); T4 N0M0: RT+ 1/2, RT- 1/5. Two of the local recurrences in irradiated patients developed in a surgical scar which was not included in the treatment volume. Significant toxicity developed in three patients (5%). It is concluded that post-operative irradiation can reduce local recurrence rate in T3 N0M0 renal cell carcinoma. It is recommended that the surgical scar should always be included in the treatment volume and irradiated to a full dose.
1. The mode of 5-hydroxytryptamine (5-HT) uptake by the rat isolated atria was studied and compared to noradrenaline (NA) uptake. 2. Rat isolated atria were incubated with 14C-5-HT (46 microM) or 3H-NA 0.4 microM). After washing, the radioactivity fixed in atria was counted and the total NA, 5-HT and 5-hydroxyindol-3-acetic acid (5-HIAA) atria contents were measured by HPLC. 3. 14C-5-HT uptake was reduced in atria from 6-hydroxydopamine (100 mg/kg, i.p., 48 hr before experiments) or reserpine (2.5 mg/kg, i.p., 24 and 48 hr before experiments) pretreated rats. 4. The incubation of atria with 5-HT (50 microM) at the same time as 3H-NA reduced the 3H-NA value fixed. 5. Addition of desipramine (1 microM) or hydrocortisone (150 microM) before the incubation of atria with 14C-5-HT was without any effect on 14C-5-HT uptake. In contrast, fluvoxamine (1 microM) or indalpine (5 microM) caused a slight inhibition. 6. These data indicate that 5-HT is taken into the NA storage vesicles within the atria sympathetic nerves. This uptake does not use the NA carrier and involves partly the 5-HT carrier. An extraneuronal accumulation was noticed and a part of it is intracellular.
1. The effect of several adrenoceptor agonists and antagonists on the spontaneous and stimulus-evoked release of [3H]noradrenaline was studied in rat isolated portal vein. 2. Yohimbine (10(-6)M) increased the stimulus-evoked [3H]noradrenaline efflux. Adrenaline alone (3 x 10(-6)M) was without effect, while it increased the resting efflux when added together with yohimbine. 3. Propranolol alone was without effect on the release of [3H]noradrenaline. When added (2 x 10(-6)M) at the same time as yohimbine, it reduced the stimulation-induced 3H efflux. When added before adrenaline and yohimbine, propranolol (10(-5)M) reduced both spontaneous and stimulus-evoked release of [3H]noradrenaline. 4. The effect of several beta-blocking drugs was measured on the enhancing effect of yohimbine on the stimulation-evoked 3H efflux. The beta 1-adrenoceptor blocking drugs: atenolol (5 x 10(-6) and 10(-5) M), metoprolol (5 x 10(-6) and 10(-5) M), like the more selective bisoprolol (2 x 10(-6) and 4 x 10(-6) M) inhibited yohimbine activity. Likewise, propranolol (2 x 10(-6) and 5 x 10(-6)M) and the beta 2-adrenoceptor blocker ICI 118551 exhibited an antagonistic effect. 5. These results indicate the possibility for noradrenaline to activate presynaptic beta-adrenoceptors in rat portal vein. They show an interaction between the presynpatic alpha 2- and beta-adrenoceptor mediated systems in the release of noradrenaline. They suggest the presence and the activity of facilitatory beta 1-adrenoceptors.
The genetically obese Zucker rat presents several abnormalities related to insulin and brain monoamines, which may play a role in its impaired regulation of food intake and body weight. In a previous study, the possible insulin-monoamine interplay was investigated by measuring brain monoamine and metabolite levels in the three genotypes of the Zucker strain. In addition to the expected results, insulin had a particular effect on striatal dopamine (DA) release, regardless of ponderal status and genotype. We further investigated this point in the present study, using the brain microdialysis technique in the striatum. Lean homozygous Fa-Fa rats responded as expected to insulin with regard to striatal DA release, with increases in DA and 3-methoxy-tyramine levels and decreases in dihydroxyphenylacetic acid and homovanillic acid. Lean heterozygous Fa-fa rats showed a very specific response profile, with decreases in all dopaminergic parameters, suggestive of an effect on DA synthesis rather than DA release. This further emphasizes the marked differences between homozygous and heterozygous lean rats. The obese fa-fa rats clearly fell into two populations. The first showed a profile of response to insulin similar to that of the lean Fa-fa rats, in keeping with the disturbances related to the "fa" gene. The second showed an increase in all the dopaminergic parameters. This pattern of response was, however, different from that of the Fa-Fa rats. These opposing responses in the two obese populations did not reflect differences in the blood glucose response to insulin. One explanation is that 16 wk may be a critical transition period in the development of genetic obesity, with regard to brain monoamine disturbances and the response to insulin.
There is great concern regarding maternal exposure to medications, especially in the first trimester of pregnancy because of the possible teratogenic effects. In the present study we have examined the consequences of maternal drug exposure in vivo upon placental secretion patterns of human chorionic gonadotrophin (HCG) and the relationship between the embryo and placenta in vitro. This was examined in samples obtained from various drug-exposed women following elective pregnancy termination at 8-9 weeks. The patterns of HCG secretion in superfused placental explants were different from those seen in control explants (without use of any medication). This was shown by changes in the pulse pattern and pulse frequency. In addition, the exposure of placental explants to various embryonic tissues modified HCG secretion in static cultures. In superfusion, co-perfusion with embryonic spinal cord tissue increased HCG secretion as opposed to that seen in similar incubations made with embryonic spinal cord tissue obtained from healthy women. Thus, our data suggest that maternal drug exposure alters both spontaneous hormone secretion by the placenta and the recently described embryo--placental relationship in vitro.
The activities of the fluoroquinolone WIN-57273, 14-OH clarithromycin (a human metabolite of clarithromycin), and minocycline against two virulent strains of Mycobacterium avium complex were evaluated in a model of intracellular infection and compared with that of clarithromycin. Human monocyte-derived macrophages were infected at day 6 of culture. Intracellular CFU at 60 min and intracellular and supernatant CFU on days 4 and 7 were counted after inoculation. The concentrations used, which were equal to peak levels in serum, were 3 micrograms of WIN-57273 per ml (MICs for the two strains, 1 microgram/ml), 4 microgram of 14-OH clarithromycin per ml (MICs, 8 and 2 micrograms/ml, respectively, at pH 7.4), 4 micrograms of minocycline per ml (MICs, 64 and 32 micrograms/ml, respectively), and 4 micrograms of clarithromycin per ml (MICs, 2 and 0.5 micrograms/ml, respectively, at pH 7.4). On day 7, compared with controls, WIN-57273, minocycline (P less than 0.02), clarithromycin, or different combinations of clarithromycin and the other drugs (P less than 0.001) slowed the intracellular replication of strain MO-1. 14-OH clarithromycin (P less than 0.02), clarithromycin (P less than 0.02), 14-OH clarithromycin plus clarithromycin (P less than 0.01), clarithromycin plus minocycline, or clarithromycin plus minocycline plus 14-OH clarithromycin (P less than 0.001) slowed the intracellular replication of strain LV-2. WIN-57273 was less effective than clarithromycin against strain MO-1 (P less than 0.05). Clarithromycin plus 14-OH clarithromycin plus minocycline (P less than 0.02) was more effective than clarithromycin alone against strain LV-2. Thus, clarithromycin plus minocycline, which corresponds in humans to three active molecules, may exhibit a better efficacy than clarithromycin in this model.
Sparfloxacin (50 mg/kg of body weight given subcutaneously each day), alone or in combination with ethambutol (50 mg/kg given subcutaneously each day), was examined for its therapeutic efficacy against experimental infection induced with the Mycobacterium avium complex in normal C57BL/6 mice. In addition, the potential anti-infective role of RU-40 555 (100 mg/kg given intraperitoneally each day), a drug that inhibits the cortisol receptors, was examined in the same model. Treatments were started 24 h after intravenous bacterial challenge and were continued for 21 days. Compared with controls, sparfloxacin or ethambutol decreased the CFU counts in spleens and lungs (P < 0.001). The sparfloxacin plus ethambutol combination was more effective than sparfloxacin alone in spleens (P < 0.001) but not in lungs. The sparfloxacin plus ethambutol plus RU-40 555 combination was more effective than the sparfloxacin plus ethambutol combination in spleens and lungs (P < 0.001). Thus, in this model, RU-40 555 enhanced the antibacterial activities of the antibiotics tested. Results of the study showed that normal C57BL/6 mice infected with the M. avium complex can be used for the evaluation of antimicrobial agents.
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Sera of 84 patients with Hodgkin's disease (HD) and 55 patients with non-Hodgkin's lymphoma (NHL) were examined for the presence of autoantibodies to ssDNA, dsDNA, Poly (I), Poly (G), cardiolipin, histones, RNP. Sm, Ro (SS/A), La (SS/B) and the common anti-DNA idiotype (16/6) using an enzyme-linked immunosorbent assay (ELISA). Anti-ssDNA antibodies were detected in the sera of 20 patients with lymphoma (23.8%), more among those with NHL than HD (16 vs. 4 patients p < 0.01). Anti-RNP and anti-Sm antibodies were found in 16 (21.7%) and 14 lymphoma patients (20%) respectively, significantly more than in the controls (p < 0.05) in both antibodies). These findings remained valid following subgrouping of the patients into those with HD and NHL. With all the other autoantibodies examined no significant difference could be observed in the incidence between lymphoma patients and controls. These results differ from our previous survey carried out on sera of patients with solid tumors in whom no increased frequency of any of the autoantibodies could be determined. In view of the evidence suggesting an increased risk of lymphoma in a number of autoimmune diseases our results extend this relationship to an increased incidence of autoantibodies among patients with lymphoma.
The presented study sought to determine the ability of a psycho-social model of intensive care intervention to prevent hospitalization. One hundred and thirteen patients identified as "needing hospitalization" were followed from their first intervention until their exit from the unit, and were checked again, a year after discharge. The results of our follow-up show that within the one year follow-up, the percentage of patients who had been hospitalized among the unit's patients was lower than the percentage of hospitalization common in psychiatric hospitals. This conclusion applies to patients with previous hospitalizations, as well as for patients with no previous hospitalizations. The success of the Intensive Mental Health Care Unit in preventing hospitalization was importantly demonstrated among the group of schizophrenic patients who form the largest subgroup of psychiatric hospital patients. In this study, chances of improvement and of remaining out of the hospital for the follow-up period were higher among patients who were working than when they entered the unit. A cost estimate based on the results indicates that the model tested is also a very cost effective model for intervention.
48 patients with stage I-II low-grade non-Hodgkin's lymphoma were treated by radiation and/or chemotherapy between 1970 and 1986. The histologic types were diffuse lymphocytic well differentiated, eleven patients; nodular lymphocytic poorly differentiated, 28 patients; nodular mixed, nine patients. Complete remission was obtained in 45 patients (94%). Overall survival was 83% and 68% at five and ten years, respectively. Five and ten-year relapse-free survival of complete responders was 71% and 57%, respectively. Univariate analysis of potential prognosticators showed the following to significantly increase the survival rate: one or two sites of disease (p less than 0.01), stage I (p less than 0.02), age less than 65 years (p less than 0.02), complete excision of tumor mass (p less than 0.03), and the use of radiotherapy (p less than 0.02). The extent of radiotherapy field did not affect survival. Multivariate analysis by the stepwise proportional hazards model of Cox showed that the use of radiotherapy was the factor which significantly produced better survival figures (p less than 0.03). It is concluded that two thirds of stage I-II low-grade lymphoma patients are potentially curable; radiotherapy plays a major role in the management.