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Biomedical subjects

M M Sigel

Publications and source records attributed to M M Sigel.

At least 37 records · Page 2Linked to original sources
PubMed1983

Enhancement of natural resistance to influenza virus in lipopolysaccharide-responsive and -nonresponsive mice by Propionibacterium acnes.

Lipopolysaccharide-responsive C3H/HeN mice were rendered resistant to a mouse-adapted strain of influenza (Aichi, H(3)N(2)) virus when Propionibacterium acnes was given either intranasally or intraperitoneally several days before virus infection. The time of P. acnes treatment was important since no protection was demonstrated when this agent was given either on the same day as or several days after virus challenge. In contrast, lipopolysaccharide-nonresponsive C3H/HeJ mice were not protected when P. acnes was administered intranasally at any time before infection; however, protection was demonstrated when P. acnes was given by the intraperitoneal route. Depending on the route of inoculation, P. acnes induced several distinctive immunological responses in the lungs of both C3H/HeN and C3H/HeJ mice. Intranasal inoculation was more effective in activating pulmonary macrophages in C3H/HeN than in C3H/HeJ mice. In contrast, intraperitoneal inoculation activated pulmonary natural killer cells in both mouse lines but did not activate pulmonary macrophages.

Adjuvants, Immunologic↗
PubMed1982

Selective action of alkylating agents against cells participating in suppression of antibody responses.

The effect of several alkylating agents on the induction and expression of specific suppressor cell activity induced by supraoptimal immunization (SOI) with (4 x 10(9) ) SRBC was studied. Splenocytes taken 8-28 days after SOI and transferred to normal syngeneic recipients together with optimal dose of (3 x 10(8) ) SRBC caused 70-90% suppression. By contrast splenocytes harvested 2 days after SOI did not exert a significant suppressive effect. Treatment of donor mice with 30 mg/kg BCNU, CCNU, or MeCCNU, 8 mg/kg Melphalan or as much as 200 mg/kg Cy 2 days before SOI uniformly had no effect on the subsequent development of suppressor cells. By contrast, different drugs had diverse effects when injected after SOI: both BCNU and Cy injected 2 days post SOI alleviated suppression, whereas CCNU, MeCCNU and Melphalan injected 2 days post SOI were without effect. Another diversity between BCNU and Cy was noticed when the administration of drugs was delayed further. While Cy alleviated suppression 12 days post SOI, BCNU was ineffective at this time. Dose response and time course studies revealed that the effect of Cy was most severe when injected 2 days post SOI and gradually diminished with the passage of time after SOI. These results have been discussed in the light of the current concepts of multiple cell participation in the induction and expression of suppressor cell function.

Alkylating Agents↗
PubMed1981

Splenic alterations during mammary tumorigenesis: diverse effects on different immune parameters.

An evaluation of various parameters of the immune system was undertaken in Balb/c mice transplanted with a syngeneic mammary adenocarcinoma. Increasing tumor burdens resulted in a depression of some cell mediated immune functions. In contrast, an augmentation of humoral responses was observed in tumor-bearing mice. A defect in the immunoregulatory mechanism did not appear to be responsible for the elevated humoral response as revealed in suppressor cell experiments. However, flow cytometric analysis of T and B lymphocyte levels in the spleens of mice with mammary tumors indicated that the numbers of Thy 1.2 positive cells were greatly diminished while there was only a slight increase in the proportion of cells bearing surface immunoglobulin. These splenic alterations accompanying tumor growth might be responsible for the altered immune responses observed in tumor-bearing animals.

Adenocarcinoma↗
PubMed1981

Kinetics of responses to tumor antigens and mouse mammary tumor virus in BALB/cCrgl and BALB/cfC3H mice.

Spleen cells from BALB/cCrgl mice responded to murine mammary tumor virus (MuMTV) in cell-mediated immune assays at higher levels than did the spleen cells from the syngeneic BALB/cfC3H mice. Implantation in BALB/cCrgl with a chemically induced mammary tumor and in BALB/cfCrgl mice with spontaneous mammary tumors (SMT) arising in the same strain resulted in sensitization of these animals to the antigens of their tumors. Reactivities peaked 3 weeks after transplantation, whereas no positive reactions could be detected when tumors reached maximum size. A kinetic study with the use of MuMTV antigen(s) showed that the responses of lymphocytes from BALB/cfC3H with SMT followed the same pattern as that obtained with tumor antigens, which indicated that this might be a de novo sensitization. In sharp contrast, a steady type of response to MuMTV was observed with the spleen cells from BALB/cCrgl mice; i.e., the levels of responsiveness to MuMTV did not significantly vary at any stage of tumor development. In vivo studies explored the possible relevance of the in vitro cell-mediated immunity to the host defenses. MuMTV-expressing mammary tumor cells were implanted in BALB/cCrgl and BALB/cfC3H mice. The total incidence of tumors was significantly reduced and a delay occurred in their time of appearance in BALB/cCrgl mice in relation to BALB/cfC3H animals. Thus the in vitro reactivity to MuMTV antigen(s) in BALB/cCrgl mice was found to be coincidental with a degree of protection against the development of MuMTV-expressing mammary tumors.

Animals↗
PubMed1981

Subset of spleen lymphocytes from BALB/cCrgl mice stimulated by mouse mammary tumor virus.

Lymphocytes from BALB/cCrgl mice react to mouse mammary tumor virus-associated antigen(s) when tested in in vitro blastogenic transformation assays. These mice have a low incidence (less than 1%) of spontaneous mammary tumors and are free from complete mammary tumor virions. We have studied the nature of the lymphoid cells mediating the lymphocyte transformation reaction to purified mammary tumor virus. With the use of nylon wool columns, the responder cells were found to belong to the nylon-adherent population. The T-lymphocytes were not stimulated by mammary tumor virus even in the presence of added macrophages. These results were reconfirmed with treatments of spleen cells with either anti-surface immunoglobulin and complement or anti-Thy 1 antigen and complement. Thus, B-cells seem to be the lymphoid population responsive to mammary tumor virus-associated antigen(s) in the spleen of BALB/cCrgl. The cause of this reactivity may be a result of any of the following: (a) horizontal transmission; (b) activation of spleen cells by viral host cell contaminants in mammary tumor virus preparations; (c) a nonspecific mitogenic reaction exerted by the virus in the system; (d) sensitization to mammary tumor virus-associated antigen(s) due to the expression of an endogenous virus. We present here data arguing against the first three possibilities. In recent work, we found evidence supporting the expression of mammary tumor virus-related antigen(s) on lymphoid cell surfaces of BALB/cCrgl. From these studies, we propose that the responses seen in our in vitro assays may represent a sensitization event resulting from exposure to an endogenous mammary tumor virus gene product.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗