Search PubMed⌕ Search

Biomedical subjects

J Isaacs

Publications and source records attributed to J Isaacs.

At least 37 records · Page 2Linked to original sources
PubMed1995

Ex-vivo whole blood cultures for predicting cytokine-release syndrome: dependence on target antigen and antibody isotype.

Ex-vivo whole blood assays have been evaluated for their ability to accurately predict the risk of a first-dose cytokine reaction developing in vivo following therapeutic antibody infusion. Tumour necrosis factor alpha (TNF alpha) release was rapidly detected in cultures incubated with either anti-CD52 antibodies of the human IgG1 or rat IgG2b isotype, and to a lesser extent with a human IgG4 isotype. Endotoxin contamination of the antibodies was not responsive for cytokine release, since polymixin B failed to inhibit cytokine release using concentrations of this antibiotic which neutralized the enhanced cytokine release seen from LPS-spiked antibody. A rat IgG2b antibody to CD45 and a human IgG1 anti-CD3 also induced significant TNF release, however, an aglycosyl anti-CD3 mutant devoid of adverse side-effects in vivo, did not result in cytokine release in vitro. Since the pattern of cytokine release seen following the clinical use of these antibodies was in good agreement with the findings of the ex-vivo whole cultures, this demonstrates the usefulness of this assay to predict cytokine release in vivo.

Adult↗
PubMed1994

Emphysematous cholecystitis can cause pneumoperitoneum.

A case of emphysematous cholecystitis with gall-bladder perforation, resulting in free intraperitoneal gas, is presented. It adds to only nine previous reports. A successful outcome was achieved by early surgery, combined with appropriate antibiotic therapy.

Aged↗
PubMed1993

The champions.

Explore the source record for details and available documents.

Community Participation↗
PubMed1993

Short latency vestibular evoked potentials.

Auditory responses, including the well-characterized auditory brainstem response, have been used extensively in clinical investigations. Evoked responses have not been adequately developed to investigate the vestibular system. The purpose of this study is to describe a new method for the evaluation of short-latency vestibular evoked potentials in human subjects. Standard ABR equipment is used, with a customized solid-state modification of the triggering mechanism. Signal averaging is used to record responses to multiple linear decelerations. Results indicate the presence of a short-latency wave, which is absent in vestibular-deficient subjects. The literature is reviewed and illustrative cases are presented. We believe vestibular evoked potentials are a promising new modality in investigation of vestibular physiology.

Evoked Potentials, Auditory↗
PubMed1992

Therapeutic immunosuppression of T cells.

Current immunosuppressive therapy carries a range of unwanted side effects, and tends to penalize the whole immune system. It is desirable to develop therapies that are more selective for antigen-reactive cells. As T lymphocytes use a wide range of surface receptors to interact with antigen-bearing cells and with each other, much interest is devoted to trying to develop agents that selectively block the interaction of these receptors with their ligands, and others that could be used to reprogram the immune system so that it might become tolerant to the antigens rather than attack them.

Animals↗
PubMed1992

Treatment of unruptured ectopic pregnancy with methotrexate.

Medical treatment is appropriate for patients with an unruptured tubal pregnancy who wish to preserve fertility or have medical problems associated with increased risk of anesthesia. Patients with persistent trophoblast after conservative surgery should be treated with methotrexate rather than undergo a repeat surgery. All nine of our patients with ectopic pregnancies who were treated with MTX were cured with one course of therapy. Little toxicity was observed and subsequent reproductive performance after medical treatment was comparable to that reported in the literature. Direct injection of MTX into an ectopic pregnancy under sonographic control provided an option for treatment which required little anesthesia, reduced the amount of drug and allowed the treatment of a gestation which would otherwise not be considered a candidate for the 3 dose intramuscular injection protocol (see Table 3).

Female↗
PubMed1991

[Evaluating parachute-drop stress by measuring blood lipids].

An attempt to evaluate parachute-drop related stress by determining the blood lipid profile (cholesterol, LDL, HDL, apo-A, apo-B, and triglycerides) is reported. Measurements were made on starting the parachute course, just before the first jump, and just after the third jump. On these 3 occasions 38 combat troops answered psychological questionnaires and 30 of them gave blood samples. While there were significant fluctuations in level of all blood lipids and their apoproteins, they could not be correlated selectively with presumed levels of stress. The well-known difficulties in field studies in controlling crucial factors such as the exact timing of the measurements and food intake (specific diet or fasting) make questionable the use of biochemical markers in measuring stress under the conditions of our study. It is possible that the high rate of refusal to give blood samples biased the findings.

Apolipoproteins A↗
PubMed1990

Role of calcium in the programmed death of rat prostatic glandular cells.

By using a newly developed and validated rat ventral prostatic organ culture system in which prostatic glandular cells can be induced to undergo programmed cell death, the role of an elevation in the intracellular free Ca2+ concentration in this death process was studied. By using this organ culture system, ventral prostatic glandular epithelial cells can be maintained in culture for a period of more than 14 days with a low daily rate of cell death (i.e., approximately 5% die per day) if androgen is included in the media. In contrast, if androgen is not included in the media, the daily rate of prostatic glandular cell death increases approximately 3-fold (i.e., approximately 15% die per day). With this organ culture system it has been demonstrated that the daily rate of programmed death of the glandular epithelial cells can be shifted from 5% to 15% of the cells dying per day when testosterone and 10 microM of the Ca2+ ionophore A23187 are both present in the media. Thus, when the intracellular free Ca2+ is elevated within prostatic cells by means of ionophore treatment, the daily rate of glandular cell death in the presence of testosterone is identical to that induced when testosterone is not present in the media. If the organ cultures are maintained in media lacking testosterone but containing 10 microM of the Ca2+ channel blocker nifedipine to inhibit elevations in the intracellular free Ca2+ derived from the extracellular pools, the rise in the daily rate of cell death from 5 to 15% of the cells dying per day induced by androgen ablation can be inhibited by approximately 70%. These results suggest that an increase within prostatic glandular cells in their intracellular free Ca2+ derived from extracellular Ca2+ pools is a critical early event involved in triggering the subsequent process of programmed cell death (i.e., specifically DNA fragmentation) in these cells following androgen ablation.

Animals↗
PubMed1989

Arachidonic acid transformation is not stimulated in delayed pressure urticaria.

Little is known about the molecular mechanisms or inflammatory mediators involved in delayed pressure urticaria (DPU). Pressure sufficient to provoke lesions was applied to the back of six patients with DPU. The levels of products of arachidonic acid transformation in skin exudate from the pressure challenged skin were estimated immediately after pressure was removed and 6 h later when lesions were present. These were compared to levels estimated in a similar way from unchallenged skin in these patients. Levels of leukotriene C4/D4/E4, prostaglandin E2, 12-hydroxyeicosatetraenoic acid and leukotriene B4 were not raised in lesional skin. Our results suggest that arachidonic acid metabolism is not stimulated in DPU.

Adult↗
PubMed1988

Expression of a transfected v-Harvey-ras oncogene in a Dunning rat prostate adenocarcinoma and the development of high metastatic ability.

To investigate the role of oncogenes in the development of metastatic ability by prostatic cancer, the viral-Harvey-ras (v-H-ras) oncogene was introduced into the Dunning rat prostate adenocarcinoma cell line, AT2.1 by means of DNA transfection. The AT2.1 cell line is a cloned cell line that is anaplastic, rapidly growing, and has low metastatic potential; after subcutaneous (s.c.) inoculation in syngeneic rats, fewer than 10% of inoculated rats develop distant metastases. Calcium phosphate mediated DNA transfections of AT2.1 cells were performed with the v-H-ras oncogene or with control DNA. The in vitro growth rate of cloned transfectants, which contain and express the v-H-ras oncogene is similar to that of untransfected AT2.1 cells and of control transfectants. After s.c. inoculation in syngeneic rats, all transfectants produced rapidly growing tumors with similar growth rates. While control transfectants had low metastatic ability comparable to untransfected AT2.1 cells, the H-ras expressing transfectants metastasized in over 80% of inoculated rats. While the mechanism by which nonmetastatic Dunning tumor sublines spontaneously develop high metastatic ability in vivo during serial s.c. passage has not been addressed in the present studies, these studies do demonstrate that expression of an activated H-ras oncogene can reproducibly convert a tumorigenic nonmetastatic prostatic cell line to a highly metastatic state.

Adenocarcinoma↗
PubMed1987

Inability of complete androgen blockade to increase survival of patients with advanced prostatic cancer as compared to standard hormonal therapy.

It has been proposed that early treatment of patients with advanced prostatic cancer by surgical or medical orchiectomy when combined with a direct acting antiandrogen will result in a more complete form of androgen blockade, thereby increasing response and survival rates compared to orchiectomy alone. We treated 55 patients with previously untreated advanced prostatic cancer by bilateral orchiectomy and additional administration of 50 mg. of the direct acting antiandrogen cyproterone acetate orally per day. Therefore, these patients have undergone a combination therapy that meets the requirements of the proposed complete androgen blockade. All 22 patients with metastases at hospitalization died during the first 4 years of treatment. Among the 33 patients without clinical evidence of metastases at hospitalization 18 were alive after 5 years. Retrospectively, the direct observed 5-year survival rate for the patients treated with a complete androgen blockade did not show any advantage compared to reported data with orchiectomy alone.

Aged↗
PubMed1983

Position effect in translocation (2;8) in acute lymphocytic leukemia with kappa light chain immunoglobulin expression.

We report a correlation between t(2;8) translocation in acute lymphocytic leukemia and kappa light chain immunoglobulin production. Since the kappa chain genes are on chromosome #2, this, as well as data on Burkitt lymphoma, points to the possibility of position effect on the level of gene action. Chromosome #2 in the translocation together with chromosome #8 is concerned with malignancy, while the normal homologous chromosome #2 transcribes kappa chains. This model applies to B cell leukemias and lymphomas with changes in chromosome #2 which will predictably express kappa chains. The model also applies to B-cell malignancies with changes in chromosome #22 which will predictably express lambda chains.

Aged↗
PubMed1982

Chromosomal changes associated with progression of the Dunning R-3327 rat prostatic adenocarcinoma system.

Several distinct sublines have developed upon serial passages of the original Dunning R-3327-H rat prostatic tumor. These tumors, each in different progressional stages, have been examined cytogenetically in the present study in order to explore the role of chromosomal changes in tumorigenesis. The original parent H tumor, from which all the other tumors were derived, has a normal karyotype, suggesting that visible alterations in chromosome structure are not essential in the early stages of the tumor. Nonrandom involvement of chromosome 4 in abnormalities observed in the increasingly aberrant tumors derived from the H tumor indicates that chromosomes most often affected may carry genetic material which is important in the regulation of cell proliferation and that this genetic material needs to undergo changes in the process of malignant transformation. Cytogenetic analysis of the Dunning sublines as a group indicated that the karyotypes of the tumors in later progressional stages tend to deviate more from the normal than those found in earlier stages. Comparison of chromosomal changes and phenotypic characteristics observed in this series of tumors suggested that the growth rate, dedifferentiation, and attainment of metastatic ability were related to the chromosome variation. The appearance and clonal development of tumor cells with a typical translocation, i.e. t(4;7), accelerated tumor growth rates of the differentiated tumors. Duplication of chromosomes was associated with a markedly increased growth rate and dedifferentiation of tumor cells in the anaplastic tumors. In addition, chromosomal loss from tetraploidy and development of complex rearrangements were associated with attainment of metastatic ability. These results point to the importance of chromosome changes in the development and biology of tumors.

Adenocarcinoma↗
PubMed1981

Effect of cell density on thrombin binding to a specific site on bovine vascular endothelial cells.

We studied thrombin binding to proliferating and confluent endothelial cells derived from bovine vascular endothelium. [125]thrombin was incubated with nonconfluent or confluent endothelial cells and both the total amount bound and the amount linked in a 77,000-dalton thrombin-cell complex were determined. Approximately 230,000 molecules of thrombin bound per cell in nonconfluent cultures compared to 12,800 molecules per cell in confluent cultures. Approximately 67,7000 thrombin molecules were bound in an apparently covalent complex, Mr = 77,000, with each cell in sparse cultures, whereas only 4,600 thrombin molecules per cell were bound in this complex with confluent cultures. Similar studies with [125I]thrombin and endothelial cells derived from bovine cornea revealed no difference either in the total amount of thrombin bound or in the amount bound in the 77,000-dalton complex using sparse or confluent cultures. When confluent vascular endothelial cultures were wounded, additional cellular binding sites for the 77,000-dalton complex with thrombin appeared within 24 h. A 237% increase in the amount of thrombin bound to these sites was induced by a wound which resulted in a 20% decrease in cell number in the monolayer. There was no significant increase in thrombin binding to other cellular sites at 24 h. These experiments provide evidence that the first change in thrombin binding after injury is an increase in the cellular sites involved in the 77,000-dalton complex, and suggest that thrombin binding to endothelial cells may be important in the vascular response to injury.

Animals↗
PubMed1978

Appendiceal abscess revisited.

Appendiceal abscess developed in 2% of 2,621 patients with acute appendicitis seen between 1962 and 1976. While representing a commendable decline in frequency from earlier studies, in view of the demonstrated prolonged delay in seeking medical care, further decreases in incidence could be affected by increased patient education. Sixty-one of 68 patients underwent surgical drainage of the abscess, with a 28% complication rate. Interval appendectomy was performed in 42 cases, with a 19% complication rate. Two patients (3%) died. These rates do no differ appreciably from those reported during the preantibiotic era. Recurrent appendicitis developed in only one of 13 patients not undergoing interval appendectomy during a follow-up period averaging five years. Interval appendectomy should be withheld only in those poor-risk patients in whom the 10% to 20% incidence of recurrent appendicitis seems the smaller risk.

Abscess↗