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Biomedical subjects

R E Falk

Publications and source records attributed to R E Falk.

At least 91 records · Page 5Linked to original sources
PubMed1982

A reevaluation of the putative association between the Fc gamma receptor and histocompatibility antigens on human mononuclear leukocytes.

The controversial question of an association between human Ia antigens and the FcR for immunoglobulin G has been examined. The experimental basis upon which such a relationship has been predicted was reevaluated. Human allosera with specificity for classical transplantation antigens, HLA-DR, and the related supertypic specificities MB and MT have been tested for their capacities to inhibit homologous EA rosette formation by PBM and B-CLL cells. Both immune and "nonimmune" sera inhibited rosette formation. Sera were normalized with respect to IgG concentration, and no significant quantitative differences in the observed inhibition were seen. Positive reactivity of the antisera with Ia, HLA-A, or HLA-B antigens did not influence EA binding to FcR. Furthermore, F(ab')2 of IgG from reactive sera did not inhibit rosette formation. These observations have been extended using murine reagents. A.TH anti-A.TL serum, which reacts with human Ia in binding and immunoprecipitation studies, and five monoclonal antibodies, which have been raised against human Ia and bind to monomorphic determinants, were tested for an effect on EA rosette formation. When these reagents were tested at concentrations at which they could be shown to bind to antigens on the target cell population, no inhibition of EA rosette formation by human PBM, MON or B-CLL cells could be demonstrated. The studies provide no evidence to suggest the existence of an association between Ia and the human FcR.

Animals↗
PubMed1982

Hyperthermia as a treatment for neoplasia.

The use of hyperthermia to treat malignant neoplasms is currently a "hot" issue. It has been demonstrated that heating tumour cells to 42 degrees C or above leads to their self-destruction by decreased cellular metabolism and aerobic respiration. The selective accumulation of heat in the malignant tissue at 42 degrees to 44 degrees C, compared with the temperature of normal tissue, is probably related to the different blood supply within the tumour. The historical background and the experimental and clinical results of hyperthermia are reviewed. The advantages and disadvantages of the different thermotherapy techniques currently in use are discussed. Hyperthermia is probably more efficient if combined with other antitumour treatment modalities.

Animals↗
PubMed1982

Induction of the rat in vitro plaque-forming response to sheep erythrocytes by a soluble factor(s) derived from concanavalin A-activated rat T lymphocytes.

Macrophages suppress the in vitro PFC response to sheep erythrocytes by rat spleen cells. We report the activity of a soluble factor released by rat splenic T-lymphocytes following a short incubation (60 min) with Con A (100 micrograms/ml). Culture supernatants added to rat spleen cells in the presence of SRBC significantly increased the PFC response at day 5. The effect was time and dose dependent. The Con A supernatant was effective in increasing PFC response if added to splenocytes during the first 16 h of the culture. The increased response if added to splenocytes during the first 16 h of the culture. The increased response was dose dependent giving maximum PFC at 1%. Depletion of macrophages from the spleen cell population produced a significant increase of the in vitro PFC response, but minimized the enhancing activity of the Con A supernatants. These studies suggest that an activated T-cell product can increase the antibody response to SRBC by completing the helper signal.

Animals↗
PubMed1982

Intermittent percutaneous infusion into the hepatic artery of cytotoxic drugs for hepatic tumours.

Between June 1, 1976 and Apr. 30, 1981, 157 patients were treated for inoperable cancer of the liver by intermittent percutaneous infusion of chemotherapeutic agents into the hepatic artery. The majority of these patients had metastatic colorectal cancer. The regimen of chemotherapeutic infusion evolved during the study and is described. The survival of the total group of patients is analysed according to type of cancer, extent of disease, dosage and combination of drugs. This therapeutic modality appears to benefit patients with metastases from colorectal cancer confined to the liver. The complication rate for this procedure is relatively low. The results from this study suggest that intermittent percutaneous infusion of cytotoxic agents into the hepatic artery is worthwhile for selected patients and should be studied further in combination with other forms of therapy.

Adult↗
PubMed1981

Studies into the mechanism of reversal of experimental acute hepatic failure by hepatocyte transplantation. 1.

The authors reported previously that single cell suspensions of syngeneic, allogeneic and xenogeneic hepatocytes can significantly improve survival in a rat model of acute hepatic failure induced by D-galactosamine. This report explores the mechanism by which hepatocyte transplantation reverses the toxin-induced hepatic necrosis. Radioautographic studies indicated that intraperitoneally administered hepatocytes labelled with tritiated thymidine did not repopulate the injured recipient liver. Hepatocytes irradiated with 10 000 rad (i.e., the cells were nonreplicating) also resulted in a significant (P less than 0.001) increase in animal survival when given to rats treated with D-galactosamine. Experiments with subcellular fractions of hepatocytes demonstrated that an intact cell was not required and that a heat stable "factor" (or factors) present in the cytosol fraction, which is not insulin or glucagon, is responsible for the increase in survival observed. This factor appears to increase the rate of endogenous regeneration of the injured recipient liver.

Animals↗
PubMed1981

Elimination of 51Cr-labelled target cells as a method of in vivo assessment of immune reactions.

This report describes the use of an in vivo 51Cr release assay which is able to monitor various immune reactions in the rat. This assay is able to quantitate the immune response to tumour and also to assess the relative efficacy of different immunostimulants in this tumour model. These data correlate well with survival studies in tumour-bearing rats. This assay can also measure the sensitizing effect of antigens from animals differing at both the major and minor histocompatibility locus using various routes of sensitization and various donor tissues. Allograft survival can also be correlated to in vivo 51Cr release. This method is both reproducible and specific. The in vivo 51Cr release assay is a useful and versatile means of monitoring the development of antitumour responses and the degree of sensitization to histocompatibility antigens in a variety of situations in the rat. It may therefore prove useful as a rapid method for screening new antitumour and immunosuppressive regimens to be used in various studies.

Adjuvants, Immunologic↗
PubMed1980

Cellular transplantation in the treatment of experimental hepatic failure.

The survival of Lewis rats with D-galactosamine-induced fulminant hepatic failure was prolonged if they were given intraperitoneal injections of single-cell suspensions of liver or bone marrow cells from normal rats. Suspensions of liver cells were also effective in prolonging the survival of rats with ischemia-induced hepatic necrosis. The liver cells did not act by repopulating the recipient liver.

Animals↗
PubMed1980

A 48,XXXX female with absence of ovaries.

A 16 1/2-year-old phenotypic female had primary amenorrhea, mild mental retardation, radioulnar synostosis, and other minor anomalies. Chromosome constitution of leukocytes and skin fibroblasts was 48,XXXX. Plasma levels of gonadotropins were increased, and those of estrogens, decreased consistent with ovarian failure. Laparoscopy showed a small midline uterus, and 2 fallopian tubes, and fimbriae. Neither ovaries nor gonadal streaks were seen on either side. This patient appears to represent the first instance of 48,XXXX aneuploidy with documented absence of ovaries.

Adolescent↗
PubMed1980

Selective immune stimulation during induction of allograft tolerance in the rat by radical immunosuppression.

Recent investigation of a biologically active synthetic polymer, NED 137, has demonstrated its ability to induce a B cell differentiation response to certain antigens, even in the presence of T cell depletion. In this report, the effect of T cell depletion combined with NED 137, on skin allografting, is explored in the Lewis strain rat. Animals were T cell-depleted by thymectomy, total body irradiation, and syngeneic marrow repopulation. They were then challenged with skin allografts +/- NED 137 treatment. Graft survival was significantly prolonged in the T-depleted rats regardless of treatment with NED 137. The drug did not increase the immune response to donor antigen as measured by in vivo lysis of 51Cr-labeled cells. Immunization with heterologous erythrocytes produced a low level of differentiation of IgM-producing cells in the T cell-depleted skin allografted group, but in contrast the T-depleted NED 137-treated rats had a normal response to immunization. These data suggest that selective stimulation of the humoral component of the immune response is feasible at a time when T cell-mediated function has been radically suppressed, without producing adverse effects on allograft survival.

Animals↗
PubMed1980

Allogeneic and xenogeneic hepatocyte transplantation in experimental hepatic failure.

Previous studies have demonstrated the efficacy of syngeneic hepatocyte transplantation in the treatment of D-galactosamine-induced acute hepatic failure in Lewis strain rats. This report describes the efficacy and immunological consequences of allogeneic and xenogeneic hepatocyte transplantation in the same model. The i.p. administration of allogeneic (minor and major histoincompatibility) hepatocytes or xenogeneic (rabbit or porcine) hepatocytes at a dose of 4 x 10(7) cells/rat given at 48 hr after toxin all resulted in significant improvement in survival compared to that of controls, and also comparable to the results obtained with syngeneic hepatocyte transplantation. Sensitization to i.p. allogeneic (WF) hepatocyte administration was demonstrated by in vivo 51Cr release, indirect immunofluorescent technique, and accelerated skin allograft rejection. Similarly, the in vivo 51Cr release assay was able to detect sensitization to porcine hepatocytes. Despite evidence of immunogenicity, redosing with either WF or porcine hepatocytes resulted in no overt toxicity. Furthermore, presensitization by either WF hepatocytes or skin allografts did not adversely affect survival after WF hepatocyte treatment in D-galactosamine-induced hepatic failure in Lewis strain rats. These data demonstrate that histocompatibility is not a constraint to successful hepatocyte transplantation and that repeated treatments are potentially safe and efficacious despite sensitization.

Animals↗