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Biomedical subjects

J S Abrams

Publications and source records attributed to J S Abrams.

At least 109 records · Page 6Linked to original sources
PubMed1989

Development of polyclonal and monoclonal antibodies for immunoassay and neutralization of human interleukin-4.

A rabbit antiserum to partly purified recombinant E. coli-expressed human interleukin-4 (IL-4) has been produced which neutralizes the T cell growth factor, B cell growth factor, and Fc epsilon R2/CD23 inducing activities of IL-4. The antiserum demonstrated sufficient avidity to immunoprecipitate labelled COS7-expressed recombinant human IL-4. In contrast, rabbits immunized with conjugates of various synthetic IL-4 oligopeptides produced antisera which recognized IL-4 in both enzyme-linked immunosorbent assay (ELISA) and Western blotting formats, but failed to immunoprecipitate IL-4 from solution, or to neutralize bioactivity. Two rat monoclonal antibodies, 11B4, 22C10 were produced from a rat immunized with purified COS7 cell-expressed IL-4. These IgG2a antibodies recognized both E. coli-expressed and mammalian cell-expressed (COS7 and L cell) recombinant human IL-4 in solution (immunoprecipitation), as well as on solid phase (indirect ELISA and dot-blotting). The 11B4 antibody inhibited IL-4 bioactivity at an IC50 which was 25-50-fold in molar excess of factor. Both antibodies also recognized IL-4 bound to an immobilized rabbit IgG fraction of anti-IL-4. The 11B4 antibody was used to develop an immunoenzymetric assay capable of detecting less than 100 pg of analyte/ml. Supernatants from PBL, activated under varying conditions were tested for IL-4 levels. PHA and ConA were found to induce a relatively low degree of IL-4 production by these PBL. An approximately ten-fold greater level of IL-4 production was observed when they were stimulated with A23187 in combination with PMA. Various patient sera and cell line supernatants were also tested. These IL-4 immunoreagents are important tools for further studies of IL-4 immunobiology.

Amino Acid Sequence↗
PubMed1989

Myocardial toxic effects during recombinant interleukin-2 therapy.

Arterial and pulmonary artery catheters were used to monitor the cardiopulmonary effects of recombinant interleukin-2 (rIL-2) given iv at a dose of 100,000 U/kg every 8 hours on days 1-5 to 10 patients with metastatic solid tumors. As anticipated, a severe capillary leak syndrome developed in all patients. Myocardial infarction (MI) occurred unexpectedly in three patients, as evidenced by a focal injury pattern on ECG and elevations of creatinine phosphokinase myocardial band fractions. All patients receiving rIL-2 exhibited major reductions in their left ventricular stroke work index (47 +/- 11 g.m/m2 to 29 +/- g.m/m2), an index of cardiac contractility. It remains uncertain whether the MIs were a byproduct of the capillary leak syndrome in patients with underlying coronary artery disease or whether rIL-2 directly or indirectly damages cardiac muscle.

Adult↗
PubMed1989

Phase II trial of N-methylformamide in advanced renal cancer.

N-methylformamide (NMF) (800-1,000 mg/m2 i.v. day 1) was given to 14 patients with measurable, advanced renal cell carcinoma in this Phase II trial. Treatment was repeated every 28 days. Significant toxicities included drug-induced hepatitis along with moderate nausea and vomiting. No objective responses were seen although several patients had stable disease with treatment for prolonged periods. NMF is not an active agent in renal cell cancer when administered by this schedule.

Adult↗
PubMed1989

Mechanism of autocrine stimulation in hematopoietic cells producing interleukin-3 after retrovirus-mediated gene transfer.

Endogenous expression of the interleukin-3 (IL3) gene introduced with a retrovirus vector renders hematopoietic cells autonomous of exogenous growth factor. To investigate the mechanism of autocrine stimulation, 25 clones were isolated after retrovirus transduction of IL3 into 32D-cl23 or FDC-P1 cells. Medium conditioned by these autonomous IL3-producing clones supported the growth of factor-dependent 32D cells. Although there was a severalfold variation in the amount of IL3 secreted (some clones secreted barely detectable levels), the doubling time of each clone in the absence of added IL3 was identical to that of the parental cell line maximally stimulated by exogenous IL3. Concentrated monoclonal and polyclonal antibodies, both highly effective in neutralizing exogenous IL3, were assayed for ability to inhibit autocrine growth. Minimal inhibitory effects were observed only on washed autocrine clones secreting low levels of IL3. To test the activity of cytoplasmically synthesized IL3, the nucleotides encoding the signal sequence of IL3 were deleted and replaced with an in-frame ATG in the context of a consensus translation initiation sequence. Ten 32D clones expressing this restructured IL3 genome were obtained. Despite the presence of biologically active IL3 in cell lysates, all clones remained dependent on exogenous IL3, with the same dose-response as that found for 32D cells. Our data are most compatible with a mechanism whereby endogenously produced IL3 interacts with its receptor prior to surface display.

Animals↗
PubMed1989

A novel pharmacodynamically based approach to dose optimization of carboplatin when used in combination with etoposide.

Thrombocytopenia, the dose-limiting toxicity of carboplatin, is manageable and predictable with the dosing equation: Dose (mg/m2) = (0.091) (creatinine clearance)/(body surface area) (desired percentage change in platelet count) + 86. We used this equation to dose patients receiving carboplatin (day 1) and etoposide (80 mg/m2 days 1 to 3). An initial cohort of 14 patients with non-small-cell lung cancer (NSCLC) were treated with 75% of the calculated dose of carboplatin (29 evaluable courses) as a precaution against added myelosuppression from combination chemotherapy. The observed reduction in platelets was essentially equal to the reduction in platelets predicted if patients had received carboplatin alone. Subsequently, a second cohort of 20 evaluable patients with NSCLC received the full calculated dose of carboplatin and etoposide (51 evaluable courses). There was a linear relationship between observed (o) and predicted (p) reductions in platelets. With full-dose carboplatin in combination with etoposide, there was a significantly greater carboplatin dosage administered, greater reduction in platelets, and lower platelet nadir. Among 34 evaluable patients (80 courses) there was one complete response (CR) and four partial responses (PRs) for an overall response rate of 15% (90% confidence +/- 9%). The median duration of survival for responders was 336+ days and for nonresponders was 204+ days. Therapy was well tolerated. This study, in addition, supports our concept of individualized dosing of carboplatin and the underlying pharmacokinetic/pharmacodynamic relationships and represents an interesting pharmacodynamic and quantitative approach to studying potential drug-drug interactions and defining appropriate dosages for combination chemotherapy.

Antineoplastic Agents↗
PubMed1988

Functional heterogeneity among human inducer T cell clones.

Analysis of mouse CD4+ inducer T cells at the clonal level has established that a dichotomy among CD4+ T cell clones exists with regard to types of lymphokines secreted. Mouse T cell clones designated Th1 have been shown to secrete IL-2 and IFN-gamma, whereas T cell clones designated Th2 have been shown to produce IL-4 but not IL-2 or IFN-gamma. To determine if such a dichotomy in the helper inducer T cell subset occurred in man, we examined a panel of human CD4+ helper/inducer T cell clones for patterns of lymphokine secretion and for functional activity. We identified human T cell clones which secrete IL-4 but not IL-2 or IFN-gamma, and which appeared to correspond to murine Th2 clones. In marked contrast to murine IL-2 secreting Th1 clones which do not produce IL-4 or IFN-gamma, we observed that some human T cell clones secrete IL-2, and IFN-gamma as well as IL-4. Southern blot analysis indicated that these multi-lymphokine-secreting clones represented the progeny of a single T cell. IL-4 secretion did not always correlated with enhanced ability to induce Ig synthesis. Although one T cell clone which secreted IL-2, IL-4, and IFN-gamma could efficiently induce Ig synthesis, another expressed potent cytolytic and growth inhibitory activity for B cells, and was ineffective or inhibitory in inducing Ig synthesis. These results indicate that although the equivalent of murine Th2 type cells appears to be present in man, the simple division of T cells into a Th1 and Th2 dichotomy may not hold true for human T cells.

Adult↗
PubMed1988

Development of rat anti-mouse interleukin 3 monoclonal antibodies which neutralize bioactivity in vitro.

Several rat anti-mouse interleukin 3 (IL-3) monoclonal antibodies have been developed which inhibit the biologic activity of mouse IL-3. These antibodies were produced in rats immunized with preparations of purified, recombinant mouse IL-3, obtained from transiently transfected COS7 cell supernatant. Hybridomas secreting anti-IL-3 were selected initially either on the basis of their giving a positive signal in an indirect enzyme-linked immunosorbent assay, or for their ability to inhibit the proliferation of the IL-3-dependent mouse mast cell line, MC/9. Neutralizing rat monoclonal IgG1, IgG2a, and IgG2b antibodies have been identified; these also block IL-3-induced proliferation of the NFS-60 and IC2 cell lines. These antibodies also blocked the IL-3-induced proliferation of mouse bone marrow-derived colony-forming units-culture suggesting that the same epitopes on IL-3 influence receptor recognition for both the proliferation of factor-dependent cell lines as well as normal bone marrow cells. Fab fragments produced from certain of the IgG2a-neutralizing antibodies blocked as well as the parent IgG. Antibody cross-blocking studies identified one neutralizing antibody apparently recognizing an epitope that was spatially distinct from those recognized by the other blocking antibodies tested. The development of these neutralizing rat monoclonal antibodies to mouse IL-3 should facilitate further investigation on the role of this factor in hemopoietic regulation.

Animals↗
PubMed1988

Acromioplasty for impingement with an intact rotator cuff.

This is a retrospective review of 108 patients who underwent decompressive anterior acromioplasty for chronic impingement in the absence of a full thickness rotator cuff tear. Before operation, all the patients had had shoulder pain for at least one year despite conservative treatment. At operation, the rotator cuff tendons were explored and were intact. Anterior acromioplasty, followed by rehabilitation was successful in 87% of patients. The operation was less successful in women, in those who had diminished movement before operation, who were involved in worker's compensation claims, and whose pain followed direct trauma. Appropriate selection of patients is considered the key to success.

Acromion↗
PubMed1987

Impingement syndrome in the absence of rotator cuff tear (stages 1 and 2).

Impingement syndrome affects a wide range of today's active population with various pathologies and presentations. Tendinitis can cause further subacromial loading, unless specific attention is directed at interrupting this disorder. Today's emphasis in high-risk populations, such as pitchers and swimmers, is on prophylaxis. Once symptoms occur, the majority can be successfully managed with nonoperative measures. Prolonged failure of conservative care prior to rotator cuff tear requires surgical decompression with predictable success in most. Results can be optimalized if strict attention is paid to patient selection, surgical technique, and a carefully supervised rehabilitation program following surgery.

Combined Modality Therapy↗
PubMed1986

Activation of mouse T-helper cells induces abundant preproenkephalin mRNA synthesis.

Antigenic or mitogenic stimulation of T cells induces the secretion of an array of protein hormones that regulate immune responses. Molecular cloning has contributed strongly to our present understanding of the nature of this regulation. A complementary DNA (cDNA) library prepared from a cloned concanavalin A-activated mouse T-helper cell line was screened for abundant and induction-specific cDNA's. One such randomly chosen cDNA was found to encode mouse preproenkephalin messenger RNA (mRNA). Preproenkephalin mRNA represented about 0.4 percent of the mRNA in the activated cell line but was absent in resting cells of this line. Other induced T-helper cell lines have 0.1 to 0.5 percent of their mRNA as preproenkephalin mRNA. Induced T-helper cell culture supernatants have [Met]enkephalin-immunoreactive material. The production by activated T cells of a peptide neurotransmitter identifies a signal that can potentially permit T cells to modulate the nervous system.

Animals↗
PubMed1986

Expression of murine and human granulocyte-macrophage colony-stimulating factors in S. cerevisiae: mutagenesis of the potential glycosylation sites.

Murine (m) and human (h) granulocyte--macrophage colony-stimulating factors (GM-CSF) have been expressed in large quantities in Saccharomyces cerevisiae using a secretion vector containing the promoter and leader sequences of the mating pheromone alpha-factor. Functionally active mGM-CSF was identified by a proliferation assay with a factor-dependent cell line and by a granulocyte--macrophage colony formation assay using bone marrow cells. The activity of hGM-CSF was confirmed by stimulation of granulocyte--macrophage colony formation using human cord blood cells. Murine GM-CSF with various apparent mol. wts (13, 18, 24, 34 and 40 kd, as well as a smear of higher mol. wts) was detected in yeast culture medium by protein blotting using a rat monoclonal antibody specific for the mGM-CSF N-terminal region peptide. Protein blotting using a rat monoclonal antibody specific for the hGM-CSF N-terminal region demonstrated that a 15.6-kd and higher mol. wt heterogeneous species were secreted. Mutations introduced at each of the two potential N-linked glycosylation sites in mGM-CSF showed that the 13-kd protein is not glycosylated and the major 18-kd protein is mainly glycosylated at the more C-terminal site, whereas the heterogeneous higher mol. wt species were not affected by the mutations. The N-terminal amino acid of the 13-kd protein was shown to be Ser which was four amino acids in the C-terminal direction from the fusion point.

Amino Acids↗
PubMed1986

CT evaluation of patients during treatment of advanced non-small cell lung carcinoma.

Twenty-one patients with Stage III non-small cell bronchogenic carcinoma were studied by chest radiograph and computed tomography (CT) before and after chemotherapy. In three patients (14%), the prechemotherapy CT showed measurable disease not seen on chest radiograph. Postchemotherapy CT scans showed additional measurable disease not seen on chest x-ray films in nine of 56 (16%) follow-up exams. This represented additional disease in seven of the 21 patients (33%). The CT findings resulted in a significant change in therapy in six of the 21 patients (29%).

Adult↗
PubMed1983

The absence of a relationship between cholecystectomy and the subsequent occurrence of cancer of the proximal colon.

Reports of an increased incidence of right-sided colonic cancers have coincided with an expanding knowledge of the carcinogenic potential of secondary bile acids which are increased after cholecystectomy, suggesting a possible relationship between cholecystectomy and the subsequent occurrence of proximal colonic cancer. The hospital records of 582 patients undergoing resection of colorectal cancers were reviewed. Fifty-four patients (9 per cent) had had prior cholecystectomies. The distribution of colonic cancers in these patients was identical to that in noncholecystectomized patients. To obtain a prospective view, 249 patients undergoing cholecystectomy between 1958 and 1960 were followed up to 1980. A cancer of the sigmoid colon or rectum occurred in four patients, three to 22 years after cholecystectomy. No patient was readmitted with a carcinoma of the proximal colon. These data fail to support a relationship between cholecystectomy and the subsequent development of a cancer of the cecum or ascending colon.

Adult↗
PubMed1983

Factors influencing perineal wound healing after proctectomy.

The hospital and office records of 86 patients who underwent proctectomy for cancer of inflammatory bowel disease with primary closure of the perineal wound were reviewed. Almost one fourth of all patients suffered a significant perineal wound complication, the majority of which were infections. The incidence of postoperative perineal wound complications was comparable in both groups of patients. Urinary retention occurred in 24 percent of patients who underwent abdominoperineal resection or rectal cancer, and half of these patients required transurethral resection which indicates the need for more thorough preoperative assessment of bladder function, especially in older men. The development of leg ischemia that resulted in amputation in two elderly patients who had preoperative evidence of obstructive peripheral vascular disease suggests that a synchronous two-team abdominoperineal resection with the patient in the modified lithotomy position for a prolonged period should be avoided. One third of all patients were discharged less than 10 days after surgery and two thirds within 2 weeks. Prolonged stays were more frequent in cancer patients and appeared to be related to age rather than to the development of postoperative complications. The perineal wound after abdominoperineal resection for cancer healed more rapidly and more completely than did the wound after proctectomy for inflammatory bowel disease. Fourteen percent of the inflammatory bowel disease patients did not have a healed wound 1 year after surgery. The extent of rectal cancer as determined by Duke's classification played no role in healing of the perineal wound, but women with rectal cancer healed at a slower rate than did men. The location of the exit site for wound catheters and the use of cautery and preoperative steroid therapy appeared too have no effect on the healing of the perineal wound.

Adult↗
PubMed1982

A second look at colonoscopy: indications, failures, and costs.

Results of colonoscopy and colonoscopic polypectomy in 599 patients have been reviewed. Added experience has not decreased the number of failures--failure to examine the entire colon, polyps not retrieved for histological examination ("lost polyps"), undetected ("missed") lesions, and false-negative biopsy specimens. The incidence of invasive carcinoma in polyps measuring under 1 cm is less than 1%; polypectomy should be reserved for larger lesions or demonstrated growth of small polyps. Diagnostic colonoscopy in selected patients (those with persistent gross or occult rectal bleeding but normal results from sigmoidoscopic and barium enema studies) demonstrates a causative lesion in greater than 25% and detects a cancer in 5% to 10% of patients.

Biopsy↗
PubMed1980

Multiple malignant carcinoids of the stomach.

A patient had multiple malignant carcinoids of the stomach. She is alive without evidence of recurrent disease or manifestations of the carcinoid syndrome almost seven years after total gastrectomy, demonstrating the favorable prognosis that follows aggressive surgical excision, even in the presence of lymph node metastases.

Adult↗
PubMed1980

Elective resection for colorectal cancer in Vermont: 1971--1975.

An analysis of 612 patients undergoing elective resection for colon and rectal cancer in Vermont during the period 1971 to 1975 indicates an increasing incidence of cancers of the cecum and ascending colon, an increased number of Duke's A cancers, a synchronous cancer rate of 6 percent, an overall operative mortality of 6.5 percent, a wide variance in postoperative stay and a relatively small experience per operating surgeon. Only one third of colorectal cancers can be visualized through the rigid sigmoidoscope. Better screening techniques that are simple, reliable, inexpensive and safe must be developed to locate proximal lesions before they metastasize to lymph nodes and distant sites. Further trials with stool blood testing are recommended.

Adenocarcinoma↗