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Biomedical subjects

M Rubenstein

Publications and source records attributed to M Rubenstein.

At least 73 records · Page 4Linked to original sources
PubMed1986

Adherent spleen cell production of E series prostaglandins in rats bearing variants of the R3327 Dunning prostatic adenocarcinoma: effect of cyclophosphamide.

Prostaglandins of the E series (PGE) have been implicated in many facets of immunoregulation, as well as having a possible role in metastatic dissemination. Variant sublines of the Dunning R3327 rat prostatic adenocarcinoma, differing in growth rate, hormonal responsiveness and in propensity for metastasis, were carried in Fisher X Copenhagen F1 animals. Adherent spleen cells were assayed in vitro for their ability to convert arachidonic acid to prostaglandins of the E series. These glass adherent cells presumably include the monocytic and T cell populations which have been implicated as being immunoregulatory. The results indicated that those spleen cells obtained from animals carrying the metastatic R3327-MAT-LyLu subline tumor converted more arachidonic acid to PGE's than cells derived from animals bearing non-metastatic sublines. Cyclophosphamide therapy did not alter such conversion. Multiple regulatory mechanisms for prostaglandin metabolism are suggested.

Adenocarcinoma↗
PubMed1986

Rat ventral prostate cell lysis at 2 degrees C.

In order to physically separate epithelial from nonepithelial cells, well-minced rat ventral prostate at 2 degrees C was passed through a tissue sieve, and the disrupted tissue suspended and washed several times before centrifugation on a Ficoll gradient. While limited separation of single prostate epithelial and nonepithelial cells and small aggregates could be achieved, the yield of intact undamaged cells was low, and many nuclei contaminated the 2 major cell fractions obtained from the gradient. During subsequent experiments, it became apparent that most single cells released from prostates minced at 2 degrees C rapidly lysed, yielding cytoplasmic debris and cell nuclei. Yet the morphology of red and white blood cells, examined by light microscopy, was unaffected, suggesting a soluble factor was not responsible. These results indicated that mechanical dissociation of rat ventral prostate at 2 degrees C with release of single cells was accompanied by a powerful prostate cell-associated lytic 'event', affecting both epithelial and connective tissue cells, without destruction of cell nuclei or accompanying red and white blood cells. Some properties of this process are described in this report.

Animals↗
PubMed1985

The effect of low-dose cyclophosphamide and immunologic exposure upon growth of established Dunning R-3327-G subline rat prostate adenocarcinomas.

Utilizing the Dunning rat prostate adenocarcinoma, a low dose of cyclophosphamide (CY), 30 mg/kg, administered either alone or following diethylstilbestrol (DES) therapy, was as effective as higher levels of CY (100 mg/kg) in ability to initiate tumor regression. A lower dose (10 mg/kg) of CY was initially ineffective. Animals which had been injected with tumor an additional 10 days prior to initiation of CY treatment were apparently more responsive to this mode of chemotherapy. The effect of this additional 10 days of immunologic exposure supports the belief that the activity of CY is augmented by the presence of immunologic competence. All animals which responded favorably toward therapy utilizing CY, alone or in combination with DES, were similarly able to reject subsequent tumor challenges. It is thought that low-dose CY may reduce the immunosuppressive effects observed with higher levels and presumably preserve the helper T cell population necessary to mount secondary immune responses.

Adenocarcinoma↗
PubMed1985

The effect of hormone therapy on peripheral blood leukocytic subset distribution in stage D prostatic cancer patients.

The distribution of mononuclear cell types found in the peripheral blood of patients bearing carcinoma of the prostate were compared by stage and to a control group using monoclonal antibody techniques. Patients with lower stage disease (A, B) had no significant alteration in subset distribution when compared to a control group, while those with higher stage disease (D) had significant deviations. Stage D patients had a decreased representation of helper-inducer T cells and an increased representation of suppressor-cytotoxic T cells, with an overall reduction in the total T cell content. In addition elevated levels of monocytic, granulocytic and null cells were recognized by the polyspecific OKM1 antibody. These differences were in part reversible following hormonal therapy. Such alterations in the ratios between the various T cell populations could be useful in patient staging and treatment selection.

Adult↗
PubMed1985

Immunobiology of the Dunning R-3327 rat prostate adenocarcinoma sublines: plasma and tumor effusion prostaglandins.

Enhanced production of prostaglandins (PGs) by experimentally-induced and naturally occurring tumors and their effect on tumor growth and immunosurveillance have been noted. Directed toward further evaluation of the relationship between prostatic tumor growth and its milieu, i.e., microenvironment, we investigated the possible correlation between levels of PGs, tumor size, and metastatic potential. For this purpose, the levels of PGE2 and PGF2 alpha in plasma and tumor effusions of three tumor sublines of the Dunning R-3327 rat prostate adenocarcinoma were measured: R-3327H, well-differentiated, slow-growing, and poorly metastatic; R-3327G, poorly differentiated, fast-growing, and poorly metastatic; and R-3327 Mat LyLu, anaplastic, fast-growing, and highly metastatic. The level of PGF2 alpha was highly variable with no significant differences being noted between the tumor sublines. The mean values of PGF2 alpha were, however, higher, although not significantly so, in the smaller tumors within each of the sublines. The levels of PGE2 were significantly higher in Mat LyLu effusions than those from the nonmetastasizing R-3327G and H sublines. Evaluation and comparison of the relationship between tumor burden, i.e., size versus levels of PGE2 and PGF2 alpha showed no significant differences. A vasodilator and regulator of immunological responsiveness, PGE2, may function as a modulator of tumor metastases. In consonance with studies by others elevated levels of PGE2 may possibly serve as a prognostic marker for the high metastatic potential of neoplastic cells.

Adenocarcinoma↗
PubMed1984

Relationship of arachidonic acid metabolism to indomethacin-sensitive immunoregulatory function and lymphocyte PGE sensitivity in peripheral blood mononuclear cells of disseminated solid tumor cancer patients.

The relationship between the conversion of arachidonic acid (AA) to E series prostaglandins (PGE), indomethacin-sensitive immunoregulation and lymphocyte PGE sensitivity was investigated in the peripheral blood mononuclear cells (PBMC) of normal subjects and disseminated solid tumor patients. Production of PGE was assessed by thin layer chromatography of ether-extracted glass adherent cells following a 24-hour pulse with 3H-AA. Immunoregulatory cell function was assessed in PHA-stimulated PBMC cultured in the presence of the prostaglandin synthetase inhibitor, indomethacin. Lymphocyte PGE sensitivity was assessed in PHA stimulated glass nonadherent cells cultured in the presence of 10(-8) M PGE. The cells from cancer patients demonstrated greater AA conversion to PGE and greater indomethacin sensitive immunoregulatory cell function than the cells of normal subjects. However, lymphocyte PGE sensitivity was comparable for both groups. When levels of arachidonic acid conversion to PGE were correlated to levels of indomethacin-sensitive immunoregulatory cell function by linear regression analysis, a significant correlation was found. These data suggest that the increased indomethacin-sensitive immunoregulatory cell function seen in PBMC from cancer patients can be directly correlated with increased production of E series prostaglandins by cancer patient peripheral blood monocytes.

Adult↗
PubMed1983

The instability of membrane markers expressed by human monocytes and macrophages in culture.

Surface markers were tested on freshly isolated human monocytes and following their in vitro maturation to macrophages. The markers tested were HLA-DR antigens, receptors for the Fc of IgG and complement as well as membrane markers defined by monoclonal antibodies. The results revealed a dynamic expression of some of the markers on monocytes which was influenced by several variables. The expression of the markers was modulated by the presence of different sera, by treatment with lymphokines and interferon and following the in vitro maturation of monocytes to macrophages. The most unstable marker was found to be the HLA-DR, which was modulated by all these variables. The 63D3 was affected by different sera and culture supernatant, as well as following the maturation of monocytes to macrophages, but not by lymphokines and interferon. One of the markers, the Mac 120, was found to be relatively stable and did not change significantly following the maturation of monocytes to macrophages. The Fc and complement receptors were also stable in their expression under these conditions, but were probably partially blocked in the presence of human serum. These results indicated that at least some of the heterogeneity related to the monocyte population was probably not due to the occurrence of stable subsets of cells, but rather to reversible changes in marker expression.

Adolescent↗
PubMed1983

Effects of castration and replacement of androgen on the separation of rat ventral prostate cells by Ficoll gradient centrifugation.

When regressing or growing (hypertrophic) cells from collagenase-digested ventral prostates were centrifuged on isokinetic Ficoll gradients for 6-8 min, they distributed into four fractions. Because of changes in epithelial cell morphology and density following castration to induce regression and replacement of androgens to cause cell growth, and contrary to results with normal rat ventral prostate, stromal cell fraction 2 was contaminated to a greater extent with regressing epithelial cells, as judged by their morphology and binding of radioactive androgens. However, centrifugation for 3 min increased the purity of epithelial cell fraction 4, although the yield of desired cells was reduced. Most cells from endocrine-manipulated rats were viable, as judged by exclusion of trypan blue and the initial incorporation of 3H-uridine. Cells centrifuged on a similar gradient of Percoll separated by a 'sieving' effect, which inverted the order of cellular fractions and removed red blood cells from fraction 2. Metrizamide offered no advantages, compared with Ficoll or Percoll. Neither physiologic nor pharmacologic amounts of testosterone returned the morphology of isolated epithelial cells to normal. To obtain consistent results with prostates from normal or hormone-manipulated rats, one should take care to select an active preparation of collagenase, avoid the use of very old animals, cool the tissue after it is dissociated, and do not apply undigested clumps of cells or overload the gradient. If attention is paid to these details, populations enriched in viable regressing or growing prostate epithelial or stromal cells can be obtained from hormonally manipulated rats.

Androgens↗
PubMed1982

Phenytoin removal by plasmapheresis in thrombotic thrombocytopenic purpura.

Phenytoin removal was followed in a patient undergoing plasmapheresis for thrombotic thrombocytopenic purpura. It was determined that 10% of total body phenytoin was removed with each two plasma volume exchanges, which is two to four times that reported with hemodialysis or peritoneal dialysis. During each 4- to 5-hr apheresis, serum phenytoin levels fell an average of 3.2 micrograms/ml and the phenytoin clearance by plasmapheresis was 21.9 +/- 2.1 ml/min (equal to the patient's endogenous clearance of 20.8 ml/min). Adjustment in drug doses were necessary such that, at steady state, the patient required 600 mg/day phenytoin to maintain therapeutic serum levels. These data indicate that plasmapheresis can clear the body of a significant amount of phenytoin and that increased doses may be required to maintain serum phenytoin levels. The potential use of apheresis in phenytoin overdose warrants further examination.

Adult↗
PubMed1982

Mithramycin impairs the release of 45Ca from bone induced by prostaglandin E2 or multiple myeloma sera. Implications for a novel means of local tumor control.

Some tumors release factors able to activate host osteoclasts. Mithramycin at sub-tumoricidal doses inhibits the release of calcium mediated by osteoclasts. If invasion of bone by a cancer requires activation of these cells, their intermittent "blockade' might impede the development of metastases to bone or their local extension. Fetal rat bones prelabelled with 45Ca were cultured in the presence of 10(-7) M prostaglandin E2, sera from normal individuals, or from patients with multiple myeloma. Additional samples preincubated for 3 h with 1 microgram/ml of mithramycin, were washed before culture. Compared with controls, prostaglandin E2 stimulated the release of 45Ca by 28% (5 experiments) and mithramycin inhibited release by 15% (3 experiments). Preexposure to this cytotoxic antibiotic before culture with PGE2 reduced the augmented release. Sera from 4 patients with multiple myeloma were incubated with 45Ca-labelled bones, some pretreated with mithramycin. An additional 29% release of 45Ca (4 experiments) was prevented by mithramycin. These results are consistent with the hypothesis that augmented release of 45Ca due to stimulatory factors such as prostagladins or factors in sera from patients with multiple myeloma can be partially inhibited by pretreatment with mithramycin. Possibly, intermittent blockade of host osteoclasts can impair formation of metastases to bone by cancers dependent upon their activation for this event, or reduce the extent of local invasion by established metastases. Modifying the behavior of a cancer by altering the host-response to factors which it releases represents a potential alternative to cytotoxic chemotherapy.

Animals↗
PubMed1981

Suspected arsine poisoning during the restoration of a large cyclorama painting.

Arsine poisoning is a well-recognized phenomenon generally associated with the smelting and refining of metals. However, acute episodes of arsine poisoning do occur in environments unrelated to metal processing and often go unrecognized. The incident described herein, which deals with artists working on the restoration of a famous painting, illustrates that arsine gas may evolve in any situation where nascent hydrogen comes in contact with small amounts of arsenic.

Air Pollutants↗
PubMed1980

Isolation of viable rat ventral prostate epithelial and nonepithelial cells.

A procedure is described for the dispersion, partial purification, and identification of epithelial and nonepithelial cells from the rat ventral prostate, the latter based in part upon the ability of cells to bind androgen. Since initial efforts to mechanically disrupt prostatic tissue at 2 C lysed many cells, minced rat prostates were exposed to collagenase at 37 C and further dispersed by repetitive pipetting and passage through a tissue sieve. Washed cells in culture medium were centrifuged through an isokinetic Ficoll gradient from which three visible fraction (1, 2, and 4) and a less definite fraction 3 were harvested. Characterically, fraction 1 contained cellular debris; fraction 2 contained round nucleated cells, fewer elliptically shaped cells, red blood cells, and rare free cell nuclei; fraction 3 contained somewhat larger elliptical and round cells; and fraction 4 contained larger round and elliptically shaped cells. These were epithelial cells, as judged by electron microscopy. Isolated prostate cells from rats castrated for 24 h were incubated with [3H]testosterone; 80-90% of the retained radioactivity, the majority of which was dihydrotestosterone, was associated with washed cells from fraction 4. Similar results were obtained after in vivo administration of labeled androgen and subsequent analysis of radioactivity in cells from these fractions. Histochemically and enzymatically demonstrable formalin-insensitive acid phosphatase was increased in bands 3 and 4, which were enriched in epithelial cells. Many cells in fractions 2-4 were viable before and after exposure to Ficoll, as estimated by their ability to exclude trypan blue, incorporate radioactive uridine into RNA, generate cell monolayers during 1-4 weeks of culture, and actively metabolize androgens. Compared to fraction 4, cells from fraction 2, considered to be enriched in nonepithelial cells, actively metabolized but bound much less [3H]testosterone and its metabolites. A number of epithelial cells in fraction 4 isolated from prostates dissociated at 2 C were associated with typical-C-type RNA viruses.

Animals↗
PubMed1980

Successful streptokinase therapy for catheter-induced subclavian vein thrombosis.

Synotinatuc subclavian vein thrombosis developed in a patient receiving long-term parenteral nutrition. Serial phlebograms showed progression of venous thrombosis, despite therapy with heparin. Fibrinolytic therapy with streptoikinase, monitored in the laboratory by the euglobulin clot lysis time, was strikingly successful and may be the treatment of choice for this condition if certain contraindications are absent.

Adult↗