PubMed HealthSearch

Biomedical subjects

M M Sigel

Publications and source records attributed to M M Sigel.

At least 19 recordsLinked to original sources

Cholylglycine measured in serum by RIA and interleukin-1 beta determined by ELISA in differentiating viral hepatitis from chemical liver injury.

Serum bile acids have been shown to serve as useful indicators of liver disease. We have confirmed these findings and added an analysis of interleukin-1 beta (IL-1 beta) profiles to further differentiate viral hepatitis from toxic liver damage associated with exposure to vinyl chloride (VC) or trinitrotoluene (TNT). The frequency of elevated cholylglycine (CG) was 100%, 75%, and 37.5% in viral hepatitis, VC- and TNT-linked liver injury patients, respectively. The mean levels, expressed in micrograms/dL, were 578, 507, 142, and 65 in hepatitis B, hepatitis non-A non-B, VC and TNT liver injury patients, respectively. Thus, the CG test could detect viral hepatitis and, VC liver injury, and (less frequently) liver injury associated with exposure to TNT. The mean level of IL-1 beta in patients with hepatitis type B was 424 pg/mL and hepatitis non A non B was 384 pg/mL compared with a mean of 33-40 pg/mL in those with VC or TNT-linked liver disease. The IL-1 beta detection test proved further to be an important distinguishing parameter as it was 100% positive in patients with viral hepatitis but only 12.5% to 25% positive in patients with VC/TNT-induced liver damage.

Adult

Interleukin-1 beta induces interleukin-1 alpha messenger ribonucleic acid expression in primary cultures of Leydig cells.

Previously, we have reported that interleukin-1 (IL-1) can modulate Leydig cell steroidogenesis. Recently, IL-1-like material has been shown to be present in the testis; however, the cellular source of this material remains unclear. In the present study we found that human recombinant IL-1 beta (1-100 ng/ml) caused dose-dependent increases in IL-1 alpha mRNA expression in Leydig cells. Similar to that reported in other tissues, IL-1 alpha mRNA from Leydig cells is mainly 2.2 kilobases. IL-1 alpha mRNA expression in Leydig cells was detectable as early as 2 h after the addition of IL-1 beta (10 ng/ml) and persisted for up to 24 h. Lipopolysaccharide also stimulated IL-1 alpha mRNA expression in these cells, but phorbol ester had no effect. Our results indicate that Leydig cells are a potential source of IL-1, which has both autocrine and paracrine effects.

Actins

Mouse mammary tumor virus (MMTV) antigen(s) are present on B lymphocytes of BALB/c mice.

Immunofluorescence studies using a polyvalent anti-MMTV serum revealed the presence of MMTV antigen(s) on the surface of spleen cells from the low mammary tumor incidence mouse strain BALB/cCrgl. Upon separation of the splenocytes on nylon-wool columns the populations of cells exhibiting positive fluorescence were nylon-adherent. These cells were considered to be B lymphocytes by the following criteria: presence of surface immunoglobulin (Slg), absence of Thy-1 antigens, enhanced responses to B-cell mitogens and decreased reactivity to T-cell mitogens. In order to ascertain the specificity of the cell surface immunofluorescence reaction, blocking studies were performed. Immunofluorescence was blocked by preincubation of the antiserum or with purified MMTV, but not by R-MuLV. Non-specific binding of the anti-MMTV to Fc receptors present on B lymphocytes was ruled out by the use of Fab'2 fragments of IgG from the various sera. Double label immunofluorescent studies with rhodamine-conjugated anti-mouse Slg Fab'2 fragments and rabbit anti-MMTV Fab'2 with fluorescein-conjugated goat anti-rabbit Fab'2 showed the simultaneous appearance of both labels in the nylon-adherent splenocytes. These results suggest the expression of viral polypeptide(s) encoded by an endogenous MMTV on the surface of B-type splenocytes in mice devoid of intact viral particles.

Animals

Suppressor activity of splenocytes from mice treated with Ecteinascidia turbinata extract.

Extracts of a marine tunicate, Ecteinascidia turbinata (Ete) were previously shown to be capable of suppressing humoral and cellular immune responses in vivo and in vitro. In the present work we have examined the mechanisms of suppression in Ete-treated DBA/2 and BALB/c mice. Treatment with Ete resulted in a significant splenomegaly accompanied by a diminished response to mitogenic stimulation, reaching coincident maxima of effect at days 4 to 6. Spleen size and blastogenic reaction returned to normal at 12 to 21 days. Cells from enlarged spleens inhibited blastogenic responses of normal splenocytes to Con A. Marker studies indicated that the suppressor activity was exerted by cells possessing T lymphocyte characteristics.

Animals

Characteristics of complement receptor-bearing cells in the spleens of tumor-bearing mice.

In the course of mammary tumor development, a population of nylon nonadherent cells with CR appears in the spleens of tumor-bearing mice although none are ever detected in normal mice. These cells apparently arise in response to immunologic stimulation. In a series of studies we have further characterized subsets of T cells (CR+ and CR-) with regard to their responses to mitogens in the lymphocyte transformation assay. Nylon column nonadherent cells from the spleens of tumor-bearing mice were rosetted in a complement receptor assay using EAC rosetting, and CR+ cells were separated from CR- by centrifugation in a discontinuous Ficoll gradient. CR+ T cells responded strongly to PHA and Con A and in addition responded to LPS, an activity not usually associated with conventional T cells. In contrast, CR- T cells from tumor-burdened mice responded to PHA but failed to respond to Con A or LPS.

Animals

Immunomodulation by Corynebacterium parvum. 1. Variable effects on anti-sheep erythrocyte antibody responses.

Corynebacterium parvum injected i.p. 1--16 days prior to i.p. antigen inoculation virtually abolished both IgM and IgG primary responses to 1 X 10(8) SRBC. The suppression was significantly marked at antigen doses ranging from 1 X 10(6)--1 X 10(9) SRBC but not at 5 X 10(9) SRBC. As little as 56 microgram C. parvum caused a marked suppression of the response to 1 X 10(8) SRBC. In secondary responses C. parvum given either one day before priming with 1 X 10(8) SRBC or one day before secondary challenge caused a dramatic suppression of both IgM and IgG PFC responses. In contrast with i.p. injected C. parvum, i.v. injection of the vaccine enhanced immune responses to i.p. or i.v. injected SRBC. Similarly C. parvum injected i.p. prior to i.v. immunization resulted in an augmented anti-SRBC response. An enhancement of anti-SRBC response was also noted when C. parvum was injected i.p. on the day of i.p. immunization. The suppressed responses in C. parvum injected animals could be explained partly by the reduced splenic localization of the antigen.

Animals

The initiation, progress, and diagnosis of dog bladder cancer induced by 4-aminobiphenyl.

Twenty-four beagles received 4-aminobiphenyl orally 5 days a week for 3 years. The dogs were examined cytoscopically at frequent intervals. Biopsy and surgery were performed according to predetermined criteria. Three basic patterns of carcinogen responses were seen. Negative or minimal disease was seen in four dogs. Of these, two remained completely free of neoplasia. Eleven dogs progressed slowly in their development of neoplasia with minor fluctuations in development. A rapidly progressive pattern was observed in the remaining nine dogs. A large variance in the time of onset of the first positive diagnosis of neoplasia was seen. Eleven dogs underwent surgery ranging from tumor sampling to cystectomy plus ureterosigmoidostomy. Histologic types and grades and patterns of metastasis as well as several other characteristics seemed to parallel closely human bladder cancer.

Adenocarcinoma

Tumor antigen extracts stimulate cytotoxicity against unrelated target cells.

A new cytotoxicity assay for the study of tumor antigens is described. Splenocytes from normal and mammary-tumor-bearing BALB/c mice were depleted of glass-adherent cells, exposed to various concentrations of tumor extracts and mixed with 51Cr-labelled chick red blood cells. Cytolysis evidenced by 51Cr release was determined 20 h after incubation at 37 degrees C. Lymphocytes from tumor bearers exerted no cytotoxic action per se, but became cytolytic after confrontation with immunogenic tumor extracts. Although this cytotoxicity is expressed against targets other than the cells containing the sensitizing antigen, i.e., a non-specific activity, its induction is strictly specific as evidence by the following: (1) extracts of D1-DMBA-3 tumors exerted an inductive effect only in lymphocytes from mice bearing this tumor and not in lymphocytes from normal mice; and (2) extracts of normal tissues or of a non-immunogenic mammary tumor, D1-DMBA-2, did not induce cytotoxicity in lymphocytes from normal or tumor-bearing mice. This approach may provide a useful method for in vitro determination of cell-mediated immunity in which specific reactions can be induced by tumor extracts as opposed to intact tumor cells.

Adenocarcinoma

Emergence of a subpopulation of lymphocytes bearing theta antigen and complement receptor during tumor growth.

Spleens from BALB/c mice transplanted with mammary tumors display a significant increase in the percentage of lymphocytes bearing complement receptors (CRL) while the percentage of cells bearing surface immunoglobulins (SIg) remains unchanged in comparison with that in spleens from normal animals. Upon separation on nylon columns, the increase in CRL in the spleens from tumor-bearing mice was limited to the non-adherent cell population. Simultaneous maker analysis disclosed that these CRL lacked detectable SIg. Indirect immunofluorescence indicated that these cells possessed theta antigen. Absence of SIg and the presence of theta antigen coupled with the restricted occurrence of these cells in the nylon-non-adherent population which responded to PHA and Con A but not to LPS indicate that these cells may constitute a subset of T cells. The paucity of this subpopulation of spleen lymphocytes in normal spleen suggests that their emergence is related to tumor growth.

Animals

Macrophage migration inhibition and lymphocyte stimulation with mammary tumor virus associated antigens in Balb/c mice.

Lymphocytes of MTV-negative Balb/c mice are sensitive to one or more antigens of MTV as determined by blastogenic transformation and migration inhibition assays. The lymphocytes from MTV-positive Balb/cfC3H mice are nonresponsive in these assays but become responsive after the mice have been implanted with MTV-positive tumors. The latter findings imply that there may be either a state of tolerance to MTV antigens which is broken by the tumor transplant or that the responses are directed towards antigens to which the host is not tolerant. The cause of the sensitivity of lymphocytes from MTV-negative Balb/c mice to MTV antigens has not been determined but two possible explanations are discussed: horizontal transmission and derepression of genetic information for viral antigen.

9,10-Dimethyl-1,2-benzanthracene