Biomedical subjects

C S Jolley

Publications and source records attributed to C S Jolley.

9 recordsLinked to original sources

PubMed1996

The role of inflammatory cells and cytochrome P450 in the potentiation of CCl4-induced liver injury by a single dose of retinol.

Evidence suggests that 7 days of retinol pretreatment potentiates chemical-induced liver injury by a mechanism that involves activation of Kupffer cells (KC). These studies were designed to determine if shorter dosing regimens of retinol potentiate carbon tetrachloride (CCl4). Initially, a single dose of retinol was shown to potentiate the hepatotoxicity of CCl4. Male Sprague-Dawley rats were pretreated with all-trans-retinol (75 mg/kg p.o.) 24 hr prior to KC isolation or administration of CCl4 (0.2 ml/kg i.p.). KC isolated at 24 hr after retinol released increased amounts of superoxide anion when stimulated with zymosan or phorbol myristate acetate. At 24 hr after CCl4, plasma ALT activities and histological sections of liver were examined. Retinol-pretreated rats showed a significant elevation in both enzyme leakage and centrilobular to midzonal necrosis compared to retinol vehicle controls following CCl4. Although complete protection was not seen, depletion of KC or neutrophils (PMNs) (by gadolinium chloride (GdCl3) or a PMN-depleting antibody, respectively) significantly reduced the hepatotoxicity of 1 day retinol/CCl4 liver injury. Immunohistochemical analysis of livers showed significant elevations in positive staining for ED2, ED1, and HIS48 in retinol-pretreated rats given CCl4. GdCl3 effectively reduced ED2 staining but did not greatly affect HIS48 staining. Additional studies were performed to estimate the effect of retinol on noninflammatory processes. While total cytochrome P450 was not increased, the activity and concentration of CYP2E1 were both significantly elevated after a single dose of retinol. Hepatocytes isolated from 1-day retinol-treated rats were also more susceptible to CCl4 injury, a consequence that is most likely related to elevated CYP2E1 activity. These findings suggest that a single pretreatment with retinol may potentiate CCl4 hepatotoxicity by multiple mechanisms which involve increased biotransformation and inflammatory cell activities.

Animals↗

PubMed1994

Chemoprevention of azoxymethane-induced colonic carcinogenesis by supplemental dietary ursodeoxycholic acid.

The present studies were conducted at the Universities of Chicago and Arizona to examine and compare the effects of supplemental dietary ursodeoxycholic acid to cholic acid, a known tumor promoter, and to piroxicam, a known chemopreventive agent, in the azoxymethane (AOM) model of experimental colonic carcinogenesis. Male Fischer 344 rats were utilized in these experiments. All animals were fed a basal diet (AIN-76) supplemented with 0.2% or 0.4% cholic acid, 0.2% or 0.4% ursodeoxycholic acid, 0.2% ursodeoxycholic acid plus 0.2% cholic acid, or 75 ppm piroxicam. Rats were given s.c. injections once a week for 2 weeks with AOM (15 mg/kg body wt/week) or vehicle (saline) after being fed their respective diets for 2 weeks. The rats in each group were then maintained on their respective diets for approximately 28 weeks; after sacrifice, their colons were removed and examined macroscopically and microscopically for the presence of tumors. The results of these studies demonstrated that none of the control rats fed the various diets injected with AOM-vehicle developed tumors. In groups receiving AOM, the addition of cholic acid (0.4%) caused a significant increase in the incidence of tumors. In contrast, the addition of 0.2% ursodeoxycholic acid did not promote AOM-induced colonic tumors, and when it was added to a promoting dose of cholic acid (0.2%), 0.2% ursodeoxycholic acid prevented enhancement of tumor promotion. At higher doses (0.4%), supplemental dietary ursodeoxycholic acid significantly reduced the incidence of colon tumors and cancers. Moreover, the tumor suppressive effects of 0.4% ursodeoxycholic acid exceeded that of dietary piroxicam. Our results further emphasize the important role of bile salts in modulating colonic tumor development. These studies also demonstrate for the first time that supplemental dietary ursodeoxycholic acid is a chemopreventive agent in the AOM model of experimental colonic carcinogenesis.

Animals↗

PubMed1993

Ethanol and diet-induced alterations in Kupffer cell function.

The effects of 6 weeks of alcohol feeding on phagocytic, metabolic and secretory functions as well as gene expression of hepatic Kupffer cells were evaluated in vitro using cultured Kupffer cells isolated from male Sprague-Dawley rats. The rats were fed either Teklad pelleted rat chow or the 1982 Lieber-DeCarli liquid diet containing 6% ethanol (36% calories) or the same liquid diet with maltose-dextrin isocalorically substituted for the alcohol. Weight gain was greatest in the chow-fed animals and least in those receiving ethanol. The alcohol-containing diet stimulated Kupffer cell phagocytosis, mitochondrial reduction of MTT, secretion of tumor necrosis factor (TNF) and expression of TNF mRNA. However, each of these cell functions was also enhanced by the control Lieber-DeCarli liquid diet alone and the stimulating effect of the control diet often exceeded that induced by ethanol. The results suggest that early in chronic alcohol consumption, the immune system may be stimulated by ethanol, and that during studies of ethanol-induced changes in immune system function, close attention must be given to potentially confounding effects of the diet.

Alcohol Drinking↗

PubMed1989

Computerized morphometric quantitation of cellular features in splenocytes from normal and nutrient-restricted mice.

The morphometric analysis of splenocytes reveals quantitative changes in the chromatin and cytoplasm that may be used to distinguish between cells from normally fed animals and cells from subjects fed restricted diets. Analysis of Feulgen-stained and Papanicolaou-stained cells from mice fed normal diets and mice fed either calorie-restricted diets or isocaloric but protein-restricted diets showed an approximately 10% reduction in the nuclear area and in the total optical density (TOD) of stained chromatin in cells from diet-restricted mice. Some changes in chromatin texture features were also observed. Utilization of nuclear area, TOD and one textural feature in a linear discriminant analysis produced a distinct separation of the cells from dietary-restricted mice and the cells from normally fed subjects; this was observed with both Feulgen-stained and Papanicolaou-stained cells. The cellular effect of dietary restriction was more noticeable in the cytoplasm than in the nucleoplasm; Papanicolaou-stained cells from diet-restricted animals showed a 23% reduction in the cytoplasmic TOD and a 10% reduction in the nuclear TOD. This study shows that computerized morphometric analysis may be used in place of or in conjunction with other measurement procedures and chemical tests to quantitate and differentiate cells subjected to different types and levels of nutritional stress.

Animals↗

PubMed1989

Computerized morphometric differentiation of chromatin changes in splenocytes from normal and calorie-restricted mice.

Morphometric image analysis of splenocytes obtained from mice fed calorie-restricted diets for periods of up to three weeks revealed slight but significant changes in nuclear size, nuclear texture and total amounts of stainable Feulgen-positive DNA as compared to age-and-sex-matched control cells. The cellular changes were associated with body weight loss and changes in the distribution of splenic T cells and B cells during the three weeks of dietary restriction. The reduced nuclear area and Feulgen-stained DNA may reflect an altered susceptibility of cells from nutrient-restricted sources toward acid hydrolysis. This in turn may be indicative of a temporarily altered synthesis of subcellular components, as these phenomena seem to lessen by the third week of dietary restriction.

Animals↗

PubMed1985

The immunoarchitecture of cutaneous pseudolymphoma.

The immunoarchitecture of five cutaneous pseudolymphomas was studied by staining serial sections for T- and B-cell and dendritic reticulum cell (DRC) antigens with monoclonal antibodies, and compared with that of reactive lymph nodes and cutaneous lymphoma. In four cases compartmentalization of B and T cells was observed, analogous to findings in reactive lymph nodes. In two of these cases the immunoarchitectural features were strikingly similar to those of reactive lymph nodes. Both had distinct follicles with germinal centers, and in one distinct mantle zone formation was seen. B cells in the follicles were polyclonal, with kappa chain predominance. The germinal centers showed the expected intercellular and/or dendritic pattern of immunoglobulin heavy chain, B2, and DRC-antigen expression. T cells admixed in the germinal centers were overwhelmingly of the T-helper type. The B-cell compartments in the other two cases showed some subtle immunologic evidence of aberrance, but the weight of evidence suggested reactive/aberrant rather than malignant processes. The T-cell compartments in all four cases showed a predominance of T-helper and a minority of T-suppressor/cytotoxic cells. All contrasted with the lymphomas, which showed B-cell monoclonality, markedly deranged T-subset proportions, or novel T-cell phenotypes. Although the main focus of this study was cases involving substantial populations of both B and T cells, preliminary observations were made in one case in which a predominance of T cells and prominent epidermotropism simulated mycosis fungoides. Quantitative ultrastructural analysis in this case suggested a reactive T-cell process. Leu-6-positive Langerhans cells were increased in the epidermis and dermis in all five cases, and in the dermis they were found almost exclusively in T-cell compartments. It is proposed that this distribution is the anatomic correlate to the known functional role of Langerhans cells in antigen processing/presentation and T-cell activation. In the cutaneous "lymph node equivalent," Langerhans cells are analogous to interdigitating reticulum cells of reactive lymph nodes in distribution and, probably, in function. The DRC found in the germinal centers in two cases were probably antigenically identical and functionally analogous to those in germinal centers of reactive lymph nodes. Immunologic phenotyping of serial cutaneous sections may aid in distinguishing reactive from neoplastic lymphoid lesions. Immunoarchitectural analysis promises to be a powerful tool for the study of lymphoproliferative disease.

Adult↗

PubMed1985

Immunotopography of splenic lymphoma of small cleaved B-cell type.

Using a battery of monoclonal antibodies on snap-frozen sections, we delineated the immunoarchitecture of two splenic small cleaved cell lymphomas (SCL). Both cases had light- and heavy-chain restricted immunoglobulin (lg) expression signifying replacement of splenic white pulp by a single B-cell clone. Both the monotypia and aberrant topography of lg expression in SCL contrasted with the usual polyclonal, zonal lg expression in reactive splenic B-cell zones. Pan B antigens (B1, B4, and L14) were constant in expression as expected for B-cell neoplasms, while B-cell maturation antigens (B2, IgD, and CALLA) were variably expressed, suggesting that different SCL may derive from separate phases of B-cell ontogeny. Close association of SCL with dendritic reticulum cells suggests SCL may derive from splenic secondary follicles or home to these sites. The variable T-cell component detected by a T-cell panel (Leu 1-9) indicates the substantial range of T-cell reactivity in splenic SCL. We emphasize the immunologic aberrancy of splenic SCL when compared to normal splenic B-cell immunotopography. Further, we illustrate the utility of serial tissue section immunochemistry in revealing complex neoplastic cell phenotypes and in revealing the relationships of reactive cells to neoplastic cells.

Antigens, Neoplasm↗

PubMed1984

Identification of two major B cell forms of nodular mixed lymphoma.

To resolve the controversy over the immunologic nature of nodular mixed lymphoma (NM), we examined nine cases of NM for surface antigens using both tissue section and cell suspension methods. These were contrasted with 12 cases of nodular poorly differentiated lymphocytic lymphoma. We found two major B cell types of NM, those with monoclonal immunoglobulin (SIg+)-positive nodules with an SIg+B1+B2+Ia+T- phenotype (four cases) and those with nodules devoid of immunoglobulin with an SIg-B1+B2-Ia+T- phenotype (five cases). Our SIg+ NM cases appear similar to nodular poorly differentiated lymphocytic lymphoma (SIg+B1+B2+Ia+T-), except suspension assay indicates fewer SIg+ cells in NM. In our SIg- NM cases, the neoplastic nodules consistently expressed B1 and Ia-like antigens and lacked T cells, indicating a B cell neoplasm similar to many large cell lymphomas. By demonstrating a B cell antigen in SIg- nodules, we substantially resolve the controversial NM cases previously called "null" or T cell. The two distinct immunotypes indicate the complexity of B cell antigenic expression in NM and might also explain the variable response to therapy in NM described in previous studies. Finally, we describe NM cases with the simultaneous occurrence of several stages of B cell differentiation. This suggests that some NM cases are not frozen in a single stage of B cell development but may express a range of B cell antigens. NM, then, may be a paradigm of variable, simultaneous B cell maturation.

Adult↗

PubMed1983

Immunoarchitecture of the human spleen.

New immunochemical staining techniques reveal key topographic aspects of splenic immune function. Distinct compartmentalization of B and T cells and lymphocytic subtypes within the white and red pulp of the human spleen provide a morphologic basis for division of labor in the immune response.

B-Lymphocytes↗