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Biomedical subjects

J Abrams

Publications and source records attributed to J Abrams.

At least 145 records · Page 8Linked to original sources
PubMed1989

The BCL1 B lymphoma responds to IL-4, IL-5, and GM-CSF.

Proliferation in vitro of the in vivo passaged murine B cell tumor line BCL1 has been used as a standard assay for mouse interleukin-5 (IL-5) for a number of years. We demonstrate that this line will also respond to human IL-5. The response to murine IL-5 is abrogated by transforming growth factor-beta and to a lesser extent by interferon-gamma. This suggests a possible regulatory role for these lymphokines in the proliferation of B cells induced by IL-5. Other purified recombinant lymphokines were also tested for their ability to induce BCL1 proliferation. The lymphokines IL-1, IL-2, IL-3, and IL-6 had no effect on the growth of BCL1. In contrast, IL-4 and more surprisingly granulocyte-macrophage colony-stimulating factor (GM-CSF) also induced proliferation of this cell. These effects could be inhibited by specific antibodies directed against the respective lymphokines. These data suggest that GM-CSF, as well as IL-4 and IL-5, may be yet another regulator of neoplastic and possibly even normal B-cell growth and differentiation.

Animals↗
PubMed1989

Infection-associated vascular lesions in acquired immunodeficiency syndrome patients.

Several reports have recently appeared in the literature describing "unique" non-neoplastic vascular lesions in patients with the acquired immunodeficiency syndrome (AIDS). These lesions may be mistaken clinically and histologically for Kaposi's sarcoma. The terms epithelioid angiomatosis, epithelioid or histiocytoid hemangioma, and pyogenic granuloma have all been used to describe a similar entity in which cat scratch disease bacillus (CSDB) was subsequently identified. Lesions closely resembling this entity occur in patients with bartonellosis. We report a case of a cutaneous vascular lesion on the hand of an AIDS patient in which cytomegalovirus (CMV) and organisms consistent with CSDB were both found. Simultaneous infections with CMV and CSDB have not been previously described. The presence of these organisms in and around endothelial cells may provide the common stimulus for the formation of these reactive vascular proliferations.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Phase I clinical trial with carbetimer.

Carbetimer, a low molecular weight polymer derived from ethylene and maleic anhydride, belongs to a class of chemical compounds different from previously available anticancer agents. It has shown moderate antitumor activity against the Madison 109, Lewis lung, colon 26 and M5076 ovarian carcinomas. In the human tumor stem cell assay, antitumor activity was seen against carcinomas of the breast, ovary, lung, colon and kidney. A total of 26 patients with solid tumors were entered into this trial; carbetimer was given on 5 consecutive days as a 1-2-h intravenous infusion. The dose was escalated from 1.08 to 11 g/m2/day. The drug did not induce the usual side-effects of chemotherapy: leukopenia, thrombocytopenia, alopecia and mucositis were minimal or totally absent. Gastrointestinal toxicity was limited to mild to moderate nausea and vomiting; these were observed at all dose levels and required antimetics in only two patients. The major side-effects of carbetimer consisted of hypercalcemia and neurotoxicity. Hypercalcemia was dose- and treatment duration-dependent. The precise mechanism of hypercalcemia is presently under investigation, but remains unclear. Neurotoxicity was observed only after prolonged therapy; two patients, who received cumulative doses higher than 250 g/m2, developed a peripheral neuropathy with paresthesia, decrease in sensory perception and motor weakness. One patient recovered completely; the other patient improved slightly before developing fatal brain metastases. Two patients with malignant melanoma exhibited major antitumor response; both were previously treated; after excellent partial responses to carbetimer, both were operated on and one is presently disease-free 2 1/2 years after completion of therapy with carbetimer. In conclusion, carbetimer is a new compound with an unusual pattern of side-effects and interesting antitumor activity against malignant melanoma. Its antitumor activity is presently being investigated in phase II trials.

Adult↗
PubMed1989

[Synovial sarcomas of the neck].

The synovial sarcoma is a mesenchymal tumour that is very rare in the head and neck region. This is a report on two cases. In a 30-year old patient the tumour arose near the thyroid gland and the hypopharynx. He died in spite of surgical removal, radiotherapy and chemotherapy, one year after the first symptoms. An 8-year old boy was affected by a synovial sarcoma near the hyoid bone and is without recurrence after surgical removal, radiotherapy and chemotherapy. Subsequently, the main diagnostic characteristics of these tumours are discussed. A better prognosis of the tumours associated with the hyoid bone is a remarkable fact.

Adult↗
PubMed1989

[Hypertrophy of the masseter muscle. Clinical aspects--etiology--therapy].

Masseteric muscle hypertrophy is a problem occurring in daily practice. Main complaints are isolated swelling of the masseteric muscle, myalgia, and functional disturbances of the parotid gland. Diagnosis is effected by inspection, palpation and anterior posterior radiograph. Sialography, CT, EMG are rarely used. Main points in the discussion of the aetiology are congenital genesis, the psychological factor, habits and occlusal disorders. The therapy consists of surgical reduction of the hypertrophied muscle as well as of conservative methods.

Bruxism↗
PubMed1989

Transdermal nitroglycerin in angina pectoris.

The transdermal nitroglycerin patches have been very successful nitrate formulations since their introduction in 1982. Nevertheless, considerable controversy regarding efficacy and tolerance has arisen. Nitroglycerin has multiple mechanisms of action in angina pectoris. Transdermal nitroglycerin in ointment formulation has been known to be effective in angina. The patches, when used in a dose of greater than or equal to 10 mg (24 h)-1, provide classic nitrate NTG effects in angina patients. However, the problem of nitrate tolerance is significant; in acute dosing, the transdermal patches lose their efficacy by 24 h and, with chronic dosing, appear usually to have little advantage over placebo in improvement of angina. An intermittent or interval approach to transdermal patch delivery appears to be the best method of avoiding nitrate tolerance. Current data suggest using the patches for 12 or 14 h consecutively and then removing them for 10-12 h. Such dosing strategies appear to eliminate or markedly reduce the problem of nitrate tolerance.

Administration, Cutaneous↗
PubMed1989

Pulmonary metastases in patients with low-grade endometrial stromal sarcoma. Clinicopathologic findings with immunohistochemical characterization.

Two cases of low-grade endometrial stromal sarcoma (ESS) presenting as cystic pulmonary metastases are reported. Both lung lesions were initially thought to represent examples of so-called mesenchymal cystic hamartoma. A diligent search of the past medical records in the first case revealed that a primary low-grade ESS of the uterus had been resected 27 years earlier. In the second case, a uterine tumor was seen by computed tomography scan and subsequent pathologic examination of the hysterectomy specimen established the presence of a low-grade ESS. Peritoneal metastases, present in both cases, also presented diagnostic problems until the uterine primaries were recognized. Immunoreactivity for desmin was detected in all primary and metastatic tumor sites examined. We conclude that ESS should be included among the desmin-positive spindle cell sarcomas and that metastatic ESS should be included in the differential diagnosis of "benign" mesenchymal cystic hamartoma of the lung.

Adult↗
PubMed1989

A comparison of carboplatin plus methotrexate versus methotrexate alone in patients with recurrent and metastatic head and neck cancer.

Patients with recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN) were stratified by performance status, extent of disease, and prior radiotherapy and subsequently randomized to receive carboplatin (CBDCA; Bristol-Myers, Wallingford, CT) administered intravenously (IV) monthly, initially at doses of 400 mg/m2 in combination with methotrexate (MTX) given IV weekly at doses of 40 mg/m2 or MTX alone at the same dose/schedule. Significant dose-limiting myelosuppression required CBDCA dose reductions to 300 mg/m2 and, subsequently, 200 mg/m2. Nonhematological toxicities were not significant. Our study objective was to determine whether CBDCA plus MTX produce a substantial improvement in response rate over single-agent MTX. A response rate of 50% (complete [CR] plus partial response [PR]) for CBDCA plus MTX compared with 25% for MTX was specified as the difference to be detected. We employed a two-stage study design for randomized trials that allowed for early termination of studies involving relatively ineffective treatment regimens. With this design, the study could be closed after the first stage (20 patients entered onto each treatment arm) if the number of responders to CBDCA plus MTX were not superior to MTX. Five of 20 patients responded to treatment in each arm, and we were able to conclude that the addition of CBDCA to MTX is unlikely to result in a twofold increase in response rate compared with MTX alone in this group of patients. This two-stage design represents a simple and efficient method of testing the relative efficacy of new combinations containing at least one active agent against a suitable control arm in this disease. It addresses scientific and ethical issues of continuing testing with relatively ineffective treatments, and at the same time provides a reliable method for identifying very active regimens likely to represent significant therapeutic advances.

Adult↗
PubMed1989

Cisplatin for small-cell lung cancer.

Small-cell lung cancer (SCLC) is a tumor highly sensitive to chemotherapy for which combination chemotherapy is the cornerstone of treatment. Antineoplastic activity has been shown for several agents, usually in the setting of minimal prior therapy. Active agents have minimal activity when used after previous chemotherapies. Cisplatin, which has only modest activity for SCLC, has not been adequately tested in the setting of minimal prior therapy, but is probably very active. Furthermore, response to cisplatin is probably dose-dependent. Synergy between agents is very important in treatment strategies, and cisplatin is synergistic with multiple agents. The EP combination (cisplatin, etoposide) is particularly synergistic for SCLC. Unlike most other combinations, EP produces consistent responses as a salvage regimen. When used as an initial treatment regimen or to alternate with other combinations, EP approximately produces the "state-of-the-art" anticipated results. When EP is administered with concurrent chest irradiation in limited disease, it produces response and survival results similar to more aggressive regimens. Thus, EP plus chest irradiation is a reasonable combination for patients not entering investigational studies, and EP may be the foundation for more aggressive combinations. CEP (high-dose EP, cyclophosphamide) caused an increase in response frequency in extensive disease. We added cisplatin to the combination of cyclophosphamide, doxorubicin, and etoposide (PACE). This four-drug combination pilot study was stopped early because of toxicities, and follow-up now suggests that survival may be prolonged. Further study of this and similar aggressive combinations appears warranted, and the use of colony-stimulating factors may allow for acceptable toxicity and further dose escalation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

A hierarchical model of opiate addiction. Failures of self-regulation as a central aspect of substance abuse.

In this paper, we first examine and recast the research literature on opiate addiction in the light of a hierarchical model of self-organization. The hierarchical model consists of five modes of psychological and psychobiological functioning defined epigenetically. Research and theories of opiate addiction are classified as to their primary modal emphases. We then describe failures of self-regulation as particular vulnerabilities along the first three modes of the hierarchy. A measure of this construct, the Scale for Failures in Self-Regulation (SFSR), a projective measure that utilizes Thematic Apperception Test responses, is introduced for the study of opiate addicts. The SFSR was administered to normal and opiate-addicted subjects in order to examine the predictive and explanatory power of the hierarchial model. A multivariate analysis of variance showed the addicts to have greater difficulties in self-regulatory functioning than normal subjects. In terms of the hierarchical model, the implications of these findings for the questions of severity of illness, psychotherapy technique, and future research are discussed.

Adult↗
PubMed1988

Intraperitoneal chemotherapy with cisplatin and melphalan.

Cisplatin and melphalan given ip exert a synergistic therapeutic effect against ascitic P388 leukemia in mice and have different dose-limiting toxic effects as well as favorable pharmacokinetic characteristics in ip phase I studies. We gave a total of 98 courses of cisplatin (escalated from 40 to 120 mg/m2) and melphalan (escalated from 12 to 30 mg/m2) to 30 patients with ip tumors, most of whom had residual ovarian cancer following iv cisplatin-containing regimens. Treatment was delivered in 2 L of 0.9% NaCl through a Tenckhoff catheter with or without a Port-a-Cath system every 28 days for one to nine cycles. Myelosuppression was dose-related and leukopenia was dose-limiting. The maximum tolerated dose was 120 mg of cisplatin/m2 and 20 mg of melphalan/m2. With the exception of treatment-induced nausea and vomiting, nonhematologic toxic effects were mild and no (or very little) local toxicity occurred. Pharmacokinetic analyses showed that the areas under the peritoneal concentration versus time curve averaged 16-fold and 17-fold more than the area under the plasma curve for cisplatin and melphalan, respectively. Objective responses were documented by third-look laparotomy in ovarian cancer patients with minimal (less than 2 cm) residual disease.

Adult↗
PubMed1988

Simultaneous production of IL-2, IL-4, and IFN-gamma by activated human CD4+ and CD8+ T cell clones.

In the present study, we have investigated the ability of human T cells to secrete IL-2, IL-4, and IFN-gamma. IL-4 and IFN-gamma were quantified with enzymatic immunoassays and IL-2 with a biologic assay by using the murine IL-2-dependent cell line CTLL-2. PBL, stimulated with Con A or with a combination of the phorbol ester 13-O-tetradecanoylphorbol-12-acetate and the Ca2+ ionophore A23187 secreted IL-2, IL-4, and IFN-gamma. The kinetics of the secretion of the three lymphokines was investigated with two CD4+ clones; one (GEO-2) that produced IL-2, IL-4, and IFN-gamma and another (HY640), that produced only IL-2 and IFN-gamma. Significant IL-2, IL-4, and IFN-gamma production was observed after only 8 h of activation. Maximal levels of IL-2 and IL-4 were found 20 h after the onset of the stimulation which subsequently decreased. In contrast, IFN-gamma levels continued to increase in a period up to 40 h and then leveled off. In spite of these differences in secretion, the kinetics of accumulation of mRNA did not differ. The IL-2, IL-4, and IFN-gamma mRNA were detectable 2 h after stimulation and continued to accumulate for a period up to 20 h. In a series of 22 CD4+ clones, 21 were able to secrete all three lymphokines upon stimulation. Almost all CD8+ clones were able to produce IL-2 and IFN-gamma, but only six of the 23 CD8+ T cell clones secreted IL-4. In addition, five CD4+ (allo)antigen-specific T cell clones were tested for IL-2, IL-4, and IFN-gamma secretion upon specific stimulation. Two alloantigen-specific and two tetanus toxoid-specific T cell clones secreted IL-2, IL-4, and IFN-gamma simultaneously, whereas one alloantigen-specific T cell clone secreted IL-2 and IFN-gamma, but not IL-4. A supernatant of the CD4+ T cell clone GEO-2, that contained high levels of IFN-gamma and IL-4, was unable to induce the low affinity receptor for IgE, CD23, on a Burkitt lymphoma cell line. However, after separation of IL-4 from IFN-gamma by using HPLC, the IL-4-containing fraction-induced CD23, which could be blocked by the fraction that contained IFN-gamma and by a polyclonal rabbit anti-IL-4 antiserum. Finally, the partly purified IL-4, that was devoid of IL-2, promoted the growth of the clone GEO-2.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Isolation and characterization of an expressible cDNA encoding human IL-3. Induction of IL-3 mRNA in human T cell clones.

We have isolated cDNA clones encoding human IL-3 from libraries constructed in a modified pcD mammalian expression vector by using mRNA prepared from activated human T cell clones. Amino acid sequence of human IL-3 deduced from DNA sequence of these cDNA clones agrees with that predicted from genomic sequence except at amino acid position 27. Northern blotting analysis and S1 nuclease analysis show that almost all activated T cell clones express IL-3 mRNA with kinetics similar to that observed in mouse T cell clones. However, striking difference was found in the level of granulocyte-macrophage-CSF and IL-3 mRNA expressed in activated human T cells. In contrast to mouse T cell clones, granulocyte-macrophage-CSF mRNA is expressed at least two orders of magnitude more abundant than IL-3 mRNA. Yeast Saccharomyces cerevisiae carrying human IL-3 cDNA fused downstream to alpha-factor leader sequence expressed and secreted biologically active IL-3. Several different rat anti-peptide antisera have been used to confirm the presence of human rIL-3 immunochemically. The immunoreactive human IL-3 expressed in transiently transfected COS7 cells or in yeast was observed to be heterogeneous. Human rIL-3 expressed in COS7 cells has multipotential CSF activity in semisolid cultures of bone marrow cells, and selectively induced the proliferation of My-10+ marrow or cord blood cells in liquid cultures.

Amino Acid Sequence↗
PubMed1988

A reappraisal of nitrate therapy.

Nitroglycerin and the long-acting nitrates are beneficial in stable and unstable angina pectoris and acute myocardial infarction and as adjunctive therapy in congestive heart failure. Nitroglycerin compounds relax vascular smooth muscle, producing venous, arterial, and arteriolar dilatation. These actions are modulated by stimulation of intracellular cyclic guanosine monophosphate. Nitrate efficacy in ischemic heart disease is due to peripheral venous and arterial vasodilatation that results in decreased myocardial oxygen consumption. Nitrates also dilate coronary arteries and collaterals, reverse coronary vasoconstriction, and enlarge some coronary atherosclerotic lesions. Nitrates improve exercise performance in stable angina pectoris. Intravenous nitroglycerin should be used in the initial treatment of unstable angina. Nitrates may be beneficial in myocardial infarction for control of ischemic pain, acute hypertension, and left ventricular failure. In subjects with congestive heart failure, nitrates reduce symptoms and improve exercise tolerance. Nitrate tolerance is a problem with continuous nitrate therapy. Tolerance is most likely to occur with frequent dosing or the use of long-acting nitrates, particularly transdermal nitroglycerin disks, and can be prevented or reversed with intermittent-dosing regimens.

Administration, Cutaneous↗
PubMed1988

Induction of interleukin-4-dependent IgE synthesis and interleukin-5-dependent eosinophil differentiation by supernatants of a human helper T-cell clone.

The human alloreactive T-cell clone A1 produces interleukin (IL)-4, IL-5, and granulocyte macrophage-colony stimulating factor (GM-CSF), but not IL-2 or interferon-gamma (IFN-gamma), as assessed by probing for mRNA transcripts, immunoassays, or bioassays. Supernatants from clone A1 induced IgE synthesis by normal human peripheral blood mononuclear cells. IL-4 was shown to be necessary and sufficient for the induction of IgE by clone A1 supernatants. In contrast, IgE induction by clone A1 supernatants and recombinant (r) IL-4 was inhibited by IFN-gamma. This suggests that the absence of IFN-gamma from the IL-4-containing A1 supernatants was important for their IgE-inducing ability. Supernatants from clone A1 could also specifically induce the growth of cord blood cell progenitors and their differentiation into eosinophils but not into basophils. rIL-5, but not rIL-4 or rGM-CSF, also induced eosinophil maturation. These data suggest that IL-5 secreted by clone A1 was responsible for its ability to induce eosinophil differentiation. The implications of the concomitant production of IL-4 and IL-5 by a single T-cell clone are discussed.

Cell Differentiation↗
PubMed1988

Ins(10;19) in an endometrial stromal sarcoma.

A 37-year-old woman with a history of bilateral mesenchymal cystic hamartomata of the lung was subsequently found to have low-grade endometrial stromal sarcoma. Cytogenetic analysis of the uterine tumor revealed, in all metaphases, an unusual derivative chromosome generated by the insertion of chromosome 19 into chromosome 10 at the level of its centromere [ins(10;19)(p11;p13q13)].

Adult↗
PubMed1988

Nitrates.

Nitroglycerin and the long-acting nitrates are playing an increasingly important role in cardiovascular medicine. These agents are recommended in all of the various anginal syndromes and are as effective as the beta-blockers and calcium channel antagonists. There is a definite place for nitrate therapy in treating the complications of acute myocardial infarction. These drugs are also highly effective as unloading therapy in congestive heart failure. The mechanisms of action of the nitrates are reviewed in this article. Information is provided regarding nitrate efficacy in all the major clinical syndromes in which these drugs are used. Finally, appropriate dosing strategies are suggested that should eliminate the potential problem of nitrate tolerance.

Animals↗