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Biomedical subjects

P Salem

Publications and source records attributed to P Salem.

32 records · Page 2Linked to original sources

Decrease in IgE Fc receptor expression on mouse bone marrow-derived mast cells and inhibition of paf-acether formation and of beta-hexosaminidase release by dexamethasone.

The effect of dexamethasone (DM) on the immunologic and nonimmunologic release of paf-acether and of the granule marker beta-hexosaminidase (BHEX) from mouse bone marrow-derived mast cells (BMMC) was studied. BMMC (1 X 10(6] in a modified Tyrode's solution containing 0.25% bovine serum albumin (BSA) were sensitized with an optimal dose of dinitrophenyl (DNP)-specific monoclonal IgE, and were washed before challenge with 40 ng/ml of DNP coupled to BSA. Preincubation of BMMC for 24 hr with 1 nM to 1 microM DM inhibited in a dose-dependent fashion the immunologic release of paf-acether and of BHEX as compared with control cells, with a half-maximal effect at 20 nM and 4 nM respectively. By contrast, the ionophore A23187 (1 microM)-induced release of paf-acether and of BHEX was unaffected by DM pretreatment. Finally, the antigen-induced increase in acetyltransferase activity, used as an index of cellular activation, was inhibited by 37 +/- 16% in 1 microM DM-treated BMMC as compared with untreated cells. Preincubation of BMMC with DM for 24 hr caused a dose-dependent inhibition of 125I-IgE binding to the cells, with a half-maximal effect at 14 nM. As determined by Scatchard analysis, the number of IgE Fc receptors was decreased by 55% in 1 microM DM-treated BMMC as compared with untreated cells, although the dissociation constants were comparable (control: 12.6 +/- 4.1 nM; DM-treated cells: 14.1 +/- 6.7 nM; mean +/- 1 SD; n = 3). Cytofluorometer analysis of BMMC sensitized with a saturating amount of purified monoclonal IgE, followed by addition of a fluoresceinated anti-mouse IgG (heavy and light chains), revealed a single cellular population for both DM-treated and untreated BMMC. This demonstrates that the DM-induced decrease in IgE Fc receptor expression was exhibited by every BMMC. The possible link between the decreased sensitization of the cells consequent to the reduction in IgE Fc receptor expression and the alteration of the secretory response and acetyltransferase activity was investigated. BMMC were incubated with IgE under experimental conditions giving half-sensitization of the cells. Upon antigen challenge, a 10.5 +/- 3.7% decrease in acetyltransferase activity and a 29.2 +/- 3.5% decrease in paf-acether release were observed with half-sensitized cells as compared with cells sensitized with a saturating amount of IgE.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Burkitt's lymphoma in the Middle East. A study of 34 cases.

The clinical features of 34 patients with Burkitt's lymphoma diagnosed at the American University Medical Center (AUMC) are described. Ages ranged between 3 and 20 years (median, 7 years). Seventy-three percent of the patients were younger than 8 years. Three cases occurred among siblings. The primary site of disease at presentation was the abdomen, 23 patients; jaw, 6; jaw and abdomen, 2; Waldeyer's ring, 2; and mediastinum, 1. Of those who had abdominal disease, the involvement was diffuse and extensive in abdomen and pelvis in 9, apparently confined to the ileocecal region in 5, mesenteric nodes and small intestine in 5, large intestine in 1, and ovary in 3. One patient presented with paraplegia. The bone marrow was studied in 19 patients; it was positive in 5 and suspicious in 2. None had frank leukemia. CSF was studied in 4 patients at presentation and was negative. Eight patients developed meningeal lymphoma during the course of the disease. Liver involvement was documented in 3 patients. Peripheral lymphadenopathy was observed at presentation in 11 patients (9, neck; 2, inguinal + axillary). In contrast to African Burkitt's, the majority of our patients presented with abdominal disease, and in contrast to the American form, our patients were younger with a median age similar to that of African Burkitt's. Thirty percent of the patients had jaw tumor at presentation--a figure intermediate between the African and the American Burkitt's.

Abdominal Neoplasms↗

Burkitt's lymphoma in the Middle East.

The clinical features of 30 retrospectively diagnosed cases of Burkitt's lymphoma (BL) at the American University Medical Center (AUMC) in Beirut differed from those of African Burkitt's in that the majority of the AUMC patients presented with abdominal disease, and from the American form, in that the AUMC patients were younger, with a median age similar to that of African BL patients.

Adolescent↗

Cis-diamminedichloroplatinum (II) by 5-day continuous infusion. A new dose schedule with minimal toxicity.

Ninety-six cancer patients received a total of 280 courses of cis-diamminedichloroplatinum (DDP), alone (20 patients), or in combination with other agents. DDP was given in 20 mg/m2 as a continuous 24-hour infusion daily for 5 consecutive days, repeated every 4 to 6 weeks. Patients were adequately hydrated for 12 hours prior to treatment but no diuretics or mannitol were used. Twenty percent of the patients developed no toxicity. Nausea and vomiting were lacking in 42% of 256 evaluable cycles and were mild in 36%. Nephrotoxicity was observed in four patients (5%) and was reversible on cessation of therapy in all except one. Hypomagnesemia occurred in 4% of 140 evaluable cycles. Mild ototoxicity was noted in two patients. The therapeutic efficacy of this dose schedule could not be adequately assessed, but one patient with thymoma and extensive pulmonary metastases achieved partial remission on DDP alone, and another with progressive mediastinal thymoma achieved stabilization of disease. In conclusion, this study suggests that the toxicity of the 5-day continuous infusion regimen is relatively mild. Randomized trials are indicated to evaluate the therapeutic efficacy of this new regimen, and the role of DDP in the treatment of malignant thymoma should be further explored.

Cisplatin↗

Public and individual idiotopes in the anti-poly(Glu60, Ala30, Tyr10) response: analysis by monoclonal antibodies.

From BALB/c mice immunized with anti-GAT monoclonal antibody (mAb) G5, we have obtained anti-idiotypic mAb against individual (or private) idiotopes, expressed by G5 as well as anti-GAT mAb, that are heteroclitic because they recognize poly-(Glu50, Tyr50) (GT) better than poly(Glu60, Ala30, Tyr10) (GAT). From BALB/c mice immunized with BALB/c polyclonal anti-GAT antibodies, anti-idiotypic mAb directed against public idiotopes expressed following GAT immunization in all individuals of all mouse strains tested have been obtained. Nine anti-idiotypic mAb were studied in detail. One of these mAb recognizes only polyclonal anti-GAT antibodies; the other eight recognize polyclonal anti-GAT antibodies and anti-GAT mAb. The distribution of the structures recognized by the different anti-idiotypic mAb on a battery of 20 anti-GAT mAb allows definition of two families of public idiotopes.

Animals↗

Phase II study of cis-dichlorodiammineplatinum(II) in advanced breast cancer.

Twenty-six patients with metastatic breast cancer received cis-dichlorodiammineplatinum(II) either as a single dose of 100 mg/m2 iv every 3--4 weeks or as a continuous 5-day infusion of 20 mg/m2/day at 4-week intervals. Fourteen patients were treated with the single-dose schedule and 12 patients were treated with the continuous 5-day infusion. No significant response was observed with either dose schedule. Aside from a reduction in the frequency and severity of gastrointestinal toxicity with the continuous 5-day infusion, no real difference was seen with regard to renal and hematologic toxicity with either dose schedule.

Breast Neoplasms↗

Clinical phase I-II study of cis-dichloro-diammineplatinum(II) given by continuous lv infusion.

To determine the efficacy and toxicity of cis-dichlorodiammineplatinum(II) (DDP) by a continuous iv infusion (CIVI) schedule, 34 patients with a variety of solid tumors were studied. All patients were refractory to prior chemotherapy and received a loading dose of 5 mg/m2 of DDP iv followed by 20 mg/m2 by CIVI daily for 5 days. In 25 evaluable patients, there were four (16%) complete or partial responders, nine (25%) with stable disease, and 12 (48%) with tumor progression. One complete and one partial remission were seen in two patients with disseminated basal cell carcinoma, with partial responses also seen in cervical and head and neck squamous cancer. Patients experienced renal damage (21%) and audiotoxicity (10%). Nausea and vomiting was severe in only 6%. DDP by CIVI appears to have comparable toxicity to DDP administered by other schedules; however, the diminished gastrointestinal toxicity makes the drug better tolerated by patients for whom the inconvenience of a 5-day hospitalization is less than that caused by the nausea and vomiting of rapid infusion programs.

Cisplatin↗

Responsiveness to endocrine manipulations in breast cancer after "prophylactic" castration.

Two hundred and one cases of premenopausal women with breast cancer who underwent prophylactic castration with subsequent recurrence were review to ascertain the degree of responsiveness of these patients to subsequent endocrine manipulation. We show that the standard endocrine manipulations, particularly the major ablations, retain a fair degree of activity in this group. There is a suggestion that the longer the castration-recurrence interval, the higher the chance of a response, but the difference is significant only for osseous-dominant disease. As in other patient groups, responders to subsequent endocrine manipulations live longer than nonresponders.

Adrenal Cortex Hormones↗

Guanazole (NSC-1895)--a phase I clinical study.

Two dose schedules of guanazole were used in this phase I clinical study: intermittent prolonged 5-day infusion and intermittent iv bolus twice weekly. Ninety-seven treatment observations were analyzed for toxic effects resulting from the prolonged infusion and 42 from the twice-weekly bolus schedule. The main toxic effect was bone marrow suppressions, the frequency and severity of which were intensified by prior chemotherapy or radiotherapy and repetition of guanazole therapy. The leukocyte count was affected more than the platelet count. Partial responses were observed in four patients: two with lung carcinoma, one with prostate carcinoma, and one with melanoma. Further phase II clinical studies of guanazole are indicated.

Clinical Trials as Topic↗