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P Salem

Publications and source records attributed to P Salem.

At least 19 recordsLinked to original sources
PubMed1991

Single-dose murine monoclonal antibody ricin A chain immunotoxin in the treatment of metastatic melanoma: a phase I trial.

To determine the maximally tolerated dose of a ricin A chain-conjugated antimelanoma antibody (XomaZyme-Mel), 20 patients with metastatic melanoma were treated with escalating doses of the murine immunotoxin given as single intravenous infusion over 30 minutes. The starting dose was 0.6 mg/kg and was escalated in five groups to a maximum of 1.6 mg/kg. The maximally tolerated dose was 1.25 mg/kg as three of six patients treated at 1.6 mg/kg developed unacceptable toxicity. The dose-limiting toxicity consisted of profound fatigue, myalgias, and arthralgias. These occurred within 4 days and resolved in 7 to 10 days. Other non-dose-limiting toxicities encountered consisted of hypoalbuminemia, weight gain, peripheral edema, mild hypotension, and flu-like syndrome; the severity of these was also dose related. In addition, two allergic reactions occurred, one severe. There was one durable complete response of 12+ months' duration and one brief mixed response lasting 3 months. We conclude that the maximum tolerated single dose of XomaZyme-Mel is 1.25 mg/kg. Phase I studies evaluating 1.25 mg/kg given in multiple doses at 2- to 4-week intervals and phase II studies to determine the response rate of a single 1.25 mg/kg dose are warranted.

Adult↗
PubMed1991

A neonate with bilateral refractory chylothorax--a case report.

A thirty six week gestation male baby weighing three kilogram was born to a twenty five year old mother by spontaneous vaginal delivery. At four hours of life, the baby developed respiratory distress with cyanosis and was admitted to the neonatal intensive care unit. There was clinical and radiological evidence of bilateral pleural effusion. Thoracentesis revealed a transudate. Repeated thoracentesis was necessary to relieve the respiratory distress. Subsequently, multi resistant Klebsiella aerogenes was isolated from the blood. The baby expired due to gram negative sepsis.

Adult↗
PubMed1990

Immunoregulatory functions of paf-acether. III. Down-regulation of CD4+ T cells high-affinity IL-2 receptor expression.

In the present report, we further explored the mechanisms by which 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (paf-acether), a phospholipid mediator of inflammation inhibited PHA-induced CD4+ cell proliferation. Evidence was obtained that CD4+ cells stimulated with either PHA or immobilized OKT3 in the presence of paf at concentrations that block CD4+ cell proliferation, exhibited a marked decrease in high affinity IL-2R expression. Importantly, paf did not prevent the binding of IL-2 to its receptor. Scatchard analysis of the binding data indicated that paf caused more than 50% decrease in the number of IL-2 high affinity sites per cell, whereas the receptor ligand affinity remained essentially constant. Moreover, the down-regulation of high affinity IL-2R was also accompanied by a loss of IL-2-dependent proliferative capacity. Together these data suggest that decreased expression of high affinity IL-2R may contribute to the diminished proliferative activity observed in CD4+ cells stimulated with PHA or immobilized OKT3 in the presence of paf. They further emphasize the potential role of lipid proinflammatory mediators such as paf in the regulation of T cell activation.

Antigens, CD↗
PubMed1990

Immunoregulatory functions of paf-acether. IV. Enhancement of IL-1 production by muramyl dipeptide-stimulated monocytes.

paf-Acether (paf) is a phospholipid mediator of inflammation released from monocytes along with IL-1. In this study, we have examined the role of paf on IL-1 production by human monocytes. When paf from 1 nM to 5 microM, but not its precursor lyso paf, was added to monocytes in the presence of muramyl dipeptide (MDP) or LPS, a marked increase in IL-1 activity over the value with MDP alone was observed. In contrast, paf alone had minimal activity over the same dose range. Antibodies against rHu IL-1 alpha and rHu IL-1 beta neutralized the increased IL-1 activity. Interestingly, MDP that prompts monocytes to synthesize IL-1, induced the synthesis of paf, as well. Most of the paf produced remained cell-associated and always preceded IL-1 synthesis. When the paf receptor antagonist, L-652,731 was added to monocytes, it prevented the enhancement of IL-1 activity induced by exogenous paf. In contrast, L-652,731 had little effect on MDP-induced IL-1 synthesis in the absence of exogenous paf. This may indicate that there are alternative mechanisms involved in the sequences of events leading to IL-1 production. It is also conceivable that the paf receptor antagonist is not able to compete or inhibit endogenous paf as well as it does for exogenous paf. Nevertheless, exogenous paf in association with a second signal, modulates IL-1 production from human monocytes in a positive manner. This may constitute another means through which paf can modulate inflammatory and immune reactions.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Malignant struma ovarii: report of two cases and selected review of the literature.

Malignant struma ovarii is an extremely rare tumor. Two new cases are described and current perspectives provided. Both cases are examples of the mixed form of the disease, and both were treated by surgery alone. One patient underwent total hysterectomy and bilateral salpingooophorectomy; the other had unilateral salpingo-oophorectomy. Both patients remained free of recurrent disease at 20 and 33 months from diagnosis. The controversies relating to therapy and diagnosis are discussed in detail.

Adult↗
PubMed1990

Splenic versus hepatic artery infusion of interleukin-2 in patients with liver metastases.

In an attempt to improve the therapeutic index of recombinant interleukin-2 (rIL-2) by generating or activating lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) regionally and/or in situ, we randomly assigned 28 patients with liver metastases to receive rIL-2 by continuous infusion for 5 days via either the splenic artery or the hepatic artery. Clinically significant and lasting tumor regression was observed only in two of 28 patients (7%), one in each of the two treatment arms. The maximum-tolerated daily dosage of rIL-2 was 3 x 10(6) U/m2; beyond this dosage, toxicity was excessive. Peripheral LAK cell activity measured in vitro and clinical tumor regression did not correlate. This observation, coupled with the equal distribution of regressions between the two treatment arms, raises the possibility that tumor regression, rare though it may be in response to rIL-2 administration, is largely mediated by TIL activation and not by LAK cell generation.

Female↗
PubMed1989

Presence of paf-acether in human thymus.

Paf-acether (paf) is a phospholipid mediator of inflammation endowed with major immunoregulatory properties. The present study demonstrates that human thymus contains large amounts of paf, as well as paf precursors. In addition, isolated thymic cells produced paf under ionophore stimulation. Paf from thymus exhibited the same biological and physiochemical properties as synthetic paf. The purity and molecular structure of paf from thymus were further characterized by reverse-phase HPLC and gas chromatography with electron-capture detection. These findings may have important implications since thymus microenvironment is essential in the proper development of bone marrow progenitors committed to the T cell lineage into thymocytes capable of emigrating to the periphery as functional T lymphocytes.

Animals↗
PubMed1988

Biochemical and morphological modifications in dexamethasone-treated mouse bone marrow-derived mast cells.

Addition of 1 microM dexamethasone (DM) to bone marrow-derived mast cells (BMMC) induced a time-dependent increase in cell histamine content. The latter reached a plateau of 2.5 micrograms/1 x 10(6) cells after 11 days in culture, compared with 100 ng/1 x 10(6) for untreated BMMC. Steroids, such as beta-estradiol, androsterone, and testosterone (1 microM), did not alter the histamine content of BMMC, whereas progesterone (1 microM) induced a moderate increase. Other glucocorticosteroids also enhanced histamine content, suggesting that the observed increase was specific for glucocorticosteroid. Treatment of BMMC with 1 microM DM for 14 days inhibited the Ag-induced, IgE-mediated release of histamine, beta-hexosaminidase, platelet-activating factor-acether, LTB4, and LTC4 by 65 +/- 3%, 66 +/- 1%, 93 +/- 3%, 66 +/- 2%, and 74 +/- 10%, respectively (mean +/- 1 SD, n = 3). In contrast with untreated cells which produce less than 2 ng/1 x 10(6) cells PGD2 after Ag challenge, DM-treated BMMC generated 16.8 +/- 0.3 ng/1 x 10(6) cells PGD2. Moreover, most of DM-treated BMMC became Alcian blue+/safranin+ and by ultrastructure, exhibited numerous cytoplasmic granules filled with abundant and uniform electron-dense matrix. The present results indicate that DM-treated BMMC exhibit biochemical and functional properties different from immature untreated cells, suggesting that a maturation-like process occurred in vitro during DM treatment.

Alcian Blue↗
PubMed1988

Immunoregulatory functions of paf-acether. I. Effect of paf-acether on CD4+ cell proliferation.

Paf-acether or platelet-activating factor (1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a phospholipid mediator of inflammation initially described as a potent platelet-aggregating compound. It is newly formed by a variety of cells including monocytes and is now recognized as a major mediator of cell-cell interactions. The present studies were undertaken to determine whether paf-acether could modulate T cell function. We found that addition of paf-acether to CD4+ cells cultured with phytohemagglutinin markedly inhibited the proliferative response in a dose-dependent manner. Maximal inhibition occurred when paf-acether was present during the first 24 hr of cell culture and the presence of paf-acether did not alter the kinetics of CD4+ cell proliferation. Importantly, the mechanism by which paf-acether inhibited the proliferative response was not related to inhibition of interleukin 2 (IL-2) secretion since the amount of IL-2 in cultures was not altered and addition of exogenous IL-2 failed to restore the CD4+ cell proliferative response. Further, as judged by indirect immunofluorescence, paf-acether did not inhibit IL-2 receptor expression. Taken together, these data indicate that paf-acether interferes with some processes leading to CD4+ cell proliferation. This new role for the chemically defined monokine paf-acether emphasizes the potential role of inflammatory lipid mediators in the regulation of T cell response.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Immunoregulatory functions of paf-acether. II. Decrease of CD2 and CD3 antigen expression.

Paf-acether (platelet-activating factor) is a phospholipid initially described as a potent platelet-aggregating compound. It is produced by numerous cell types and is now considered as an important mediator of cell-cell interactions. The effect of paf-acether on the expression of CD2 and CD3, two human T cell surface glycoproteins, was investigated by indirect immunofluorescence and flow cytometry. Paf-acether partially down-regulated, in a time- and dose-dependent manner, CD2 and CD3 but not HLA class I antigen expression on peripheral human T cells and Jurkat cells. Lysophosphatidylcholine, a phospholipid closely related to paf-acether, had no detectable modulatory effect on CD2 and CD3 expression. In addition to CD2/CD3 modulation, paf-acether markedly inhibited T cell proliferative response not only to phytohemagglutinin or concanavalin A but also to anti-CD3 or a stimulatory combination of anti-CD2 monoclonal antibodies. These data demonstrate for the first time that lipid mediators such as paf-acether might be involved in the regulation of the expression of cell surface glycoproteins that are essential in the execution of T cell function.

Antibodies, Monoclonal↗
PubMed1987

Primary small intestinal lymphoma in adults. A comparative study of IPSID versus non-IPSID in the Middle East.

Seventy-five cases of primary small intestinal lymphoma (PSIL) were diagnosed in adults at the American University of Beirut Medical Center (AUBMC) during the period from 1961 to 1980. Two additional cases of immunoproliferative small intestinal disease (IPSID) in the premalignant phase also were studied. Thirty-two patients had IPSID; 27 non-IPSID; and in 18 patients it was difficult to distinguish IPSID from non-IPSID. While the former was shown to be a distinct disease entity with characteristic clinical, pathologic, and immunologic features, the latter was found to have no particular features in this part of the world. In addition to alpha heavy chain protein (AHCP) which is the biological marker of IPSID, the most important finding that distinguished the two diseases was that IPSID was always associated with a dense, compact mucosal cellular infiltrate (MCI) that was continuous and uninterrupted all along the length of the small intestine. In non-IPSID, MCI was lacking and the pathology was confined to sites of gross abnormalities. Sites distant to the primary lesion were free of disease. It was reported previously that the MCI in IPSID is characteristically diffuse plasmacytic or lymphoplasmacytic (DLP). Our study indicates that in addition to this infiltrate, the disease may be associated with another type of infiltrate which is follicular lymphoid (FL). Sixteen patients had DLP; ten, FL; and three, mixed infiltrate. The relationship of AHC disease and IPSID is discussed. AHCP may be found in intestinal fluid, serum, within the abnormal cell, or at its surface. Immunofluorescence and immunoperoxidase studies must be done on all intestinal and nodal tissue specimens in all patients with PSIL for the detection of AHCP, particularly in those where serum and intestinal fluid are negative for this protein. The hypothesis that the DLP infiltrate represents the secretory form of IPSID, while the FL the nonsecretory form, is introduced. IPSID is an ideal model for the study of the etiology and pathogenesis of lymphoma in man.

Adolescent↗
PubMed1987

Primary lymphoma in the salivary glands: report of five cases and review of the literature.

The finding of a lymphoma in a major salivary gland could mean one of two things: either it is part of a disseminated process, or it is the first clinicopathologic evidence of lymphoma. In the latter instance, whether the disease originated in the glandular stroma itself or in a paraglandular lymph node and then invaded the stroma, the lymphoma is defined as primary, as long as there is no detectable disease outside the salivary gland. Five cases of primary salivary gland lymphomas are described. All had a complete clinical staging including chest x-ray, bilateral bone marrow biopsy, liver-spleen scan, bilateral pedal lymphangiography and/or abdominal CT scan. There was no evidence of lymphoma outside the gland in any of the patients described; hence, these can be labeled as primary lymphomas of the salivary gland. Review of the literature suggests that this presentation of the disease is extremely rare. Although 324 cases of salivary gland lymphomas have been described in the literature, only six may be considered primary by our criteria. The remaining patients were either not adequately staged or had documented evidence of disease elsewhere at the time of diagnosis. The diagnosis of primary salivary gland lymphoma should not be made unless complete staging is performed.

Adenolymphoma↗
PubMed1986

Non-Hodgkin's lymphomas in the Middle East. A study of 417 patients with emphasis on special features.

A total of 417 evaluable patients with non-Hodgkin's lymphomas were diagnosed between January 1974 and December 1983 at the American University of Beirut Medical Center in Beirut, Lebanon. Of these, 179 (43%) patients had nodal lymphomas, and 183 (44%) had extranodal lymphomas. The commonest lymphoma was diffuse large cell (27%), followed by large cell immunoblastic (21%). The histopathologic pattern was follicular in 18% of the nodal lymphomas and in 5.3% of the extranodal forms. The most common site of extranodal lymphoma was the gastrointestinal tract (46.5%), followed by Waldeyer's ring (19%). Small intestinal lymphomas were three times more common than gastric lymphomas. Immunoproliferative small intestinal disease (IPSID) was diagnosed in 20 of 59 patients who had primary small intestinal lymphoma. Of the 34 patients who had Waldeyer's ring lymphoma, 7 had gastrointestinal involvement at some time during the course of the disease. Nodal lymphomas were associated with poor prognostic factors: 82% were diffuse; 77% had advanced disease at presentation; 77% had intermediate- or high-grade malignancy lymphoma; 40% had marrow involvement; and 46% had B symptoms. In children, the most common lymphoma was Burkitt's, and 80% of pediatric lymphomas were high-grade malignancy. In conclusion, this study delineates the special features of non-Hodgkin's lymphomas in the Middle East: The presence of IPSID; the high incidence of extranodal forms, in particular the intestinal ones; and the rarity of follicular lymphomas.

Adolescent↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1978

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↗