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Biomedical subjects

J A Falk

Publications and source records attributed to J A Falk.

At least 55 records · Page 3Linked to original sources
PubMed1981

Acute myeloblastic leukemia-associated antigens: detection and clinical importance.

Antigenic compounds from the surface of leukemic myeloblasts are shed in vitro on short-term culture. Blast cells radiolabeled by lactoperoxidase iodination release soluble compounds that react immunologically with alloantisera to leukemia-associated antigens. Partially characterized soluble antigens were used to raise heteroantisera in monkeys that are selectively reactive with leukemic myeloblasts and unreactive with nonleukemic cells. Monkey heteroantisera were used to further characterize soluble leukemia antigens. Sera from patients with acute myeloblastic leukemia inhibit the reactivity of the heteroantisera, suggesting that soluble leukemic antigen is released in vivo as well.

Antibodies, Neoplasm↗
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

The prognostic value of HLA phenotypes in Hodgkin's disease.

Analysis of a group of 79 patients with previously untreated Hodgkin's disease, whose HLA phenotypes were determined in 1972-73, shows that patients in a sub-group with the specificities collectively known as Aw19 have significantly poorer survival than patients without these specificities. The degree to which the serologically-detectable HLA antigens assist in determining the prognosis for survival has been analyzed using multiple regression analysis and retrospective stratification. Both approaches indicate that the association of HLA phenotype with survival is not accounted for by correlations between HLA antigens and other know prognostic factors, such as stage, histology, age, and sex. The greatest prognostic value of Aw19 appears to be for patients with relatively unfavorable age (greater than 40 years), stage (III and IV), or histology (lymphocyte depletion, mixed cellularity).

Adult↗
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↗
PubMed1980

Comparison of the antitumor effects of a synthetic biopolymer and standard adjuvants.

The synthetic biopolymer NED 137 is capable of stimulating an immune response to tumor antigen. This article compares the efficacy of NED 137 to bacille Calmette-Guerin, Corynebacterium parvum, pyran, levamisole, and Freund's complete adjuvant in a rat tumor model where adjuvant treatment is administered after excision of subcutaneous tumor implants. A single intraperitoneal injection of NED 137 at 30 mg/kg body weight prolonged survival beyond 60 days with no evidence of recurrent or metastatic disease, whereas with the other adjuvants, animals survived a mean of 30 to 40 days with 100% local recurrence and a 60% to 90% incidence of pulmonary metastases. Use of NED 137 resulted in a greater lysis of tumor cells compared to other adjuvants when assessed in an in vivo 51Cr release assay. A phase I clinical study of high-risk gastrointestinal cancer patients treated with NED 137 is reported at a median survival time of 23 weeks (103 patients). This group is compared to a historical control group from the same institution. No NED 137-related toxicity has been noted to date.

Adenocarcinoma↗
PubMed1980

Reversal of toxic and anoxic induced hepatic failure by syngeneic, allogeneic, and xenogeneic hepatocyte transplantation.

This report describes the efficacy of syngeneic hepatocyte transplantation in an anoxic model and of xenogeneic (rabbit and porcine) hepatocyte transplantation in a toxic model of fulminant hepatic failure in the rat. Lewis strain rats that received 4 X 10(7) hepatocytes intraperitoneally at 48 hours after hepatic artery ligation had a significantly improved survival rate (79%, n = 14) when compared with control animals (38%, n = 21, P less than 0.05). Xenogeneic hepatocytes (4 X 10(7) cells/rat) given intraperitoneally to D-galactosamine-poisoned Lewis rats at 48 hours after toxin administration were able to significantly improve survival rate as compared with controls (71% versus 14%, n = 14, P less than 0.01 for rabbit; and 75%, n = 14 versus 12.5%, n = 16, P less than 0.001 for porcine). Although an increase in in vivo cytotoxicity could be demonstrated after procine hepatocyte transplantation, no adverse clinical effects were observed. The methodology for the harvest and storage of large numbers of hepatocytes from a large animal liver has been developed, and it is now feasible to proceed to the clinical application of hepatocyte transplantation for human fulminant hepatic failure.

Animals↗
PubMed1979

Early diagnosis of relapse in acute myeloblastic leukemia: Serologic detection of leukemia-associated antigens in human marrow.

We tested serial bone-marrow samples from 47 adults with acute myeloblastic leukemia in remission for reactivity with heteroantiserums to leukemia-associated antigens, to determine whether imminent relapse could be detected in patients with acute leukemia. Of 26 patients who relapsed by standard morphologic criteria, 21 had increased immunoreactivity of bone marrow for one to six months (mean, 3.7 months) before relapse. High concordance was observed between a positive test and relapse during the period of study (chi-square = 27.53, P less than 0.001). The median time to relapse after a positive test was four months, as compared with the median remission duration of 19 months for the whole group (P less than 0.02, Peto's log-rank analysis). Serologic detection of leukemia-associated antigens in marrow may be a reliable indicator of imminent relapse in acute myeloblastic leukemia.

Animals↗