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Biomedical subjects

D W Scott

Publications and source records attributed to D W Scott.

At least 91 records · Page 5Linked to original sources
PubMed1992

Can peritoneal B cells be rendered unresponsive?

Ly-1+ B cells have been reported to produce a number of autoantibodies, and to be involved in the selection and regulation of the conventional B cell repertoire. It is not known if these B cells, which are found in high numbers in the peritoneum of normal adult mice, themselves can be regulated. In this study, we evaluated the sensitivity of peritoneal B cells (PBCs) versus conventional splenic B cells to regulation in a model system for tolerance. Normal splenic (conventional) or PBCs (containing both CD5+ and CD5- 'sister' cells) were cultured overnight with either F(ab')2 or intact IgG anti-mouse Ig, washed, and then challenged with fluorescein(FL)-coupled to Brucella abortus (BA), trimethylammonium (TMA)-BA or lipopolysaccharide (LPS), and the IgM responses to the FL and TMA haptens measured. In contrast to spleen cells, which exhibited up to a 90% reduction in anti-FL responsiveness, pretreated PBCs were mostly resistant to this form of tolerance regardless of challenge. The anti-TMA response of PBCs, which reflects the skewed VH11 usage by peritoneal CD5 B cells, was also resistant to tolerance. However, splenic TMA-specific B cells appeared to be sensitive to unresponsiveness induced by anti-Ig. Signaling studies show that PBCs have a blunted initial Ca2+ response, suggesting that the consequence of anti-Ig crosslinking may be defective in these cells. Furthermore, phorbal myristate acetate and/or ionomycin treatment of both PB and splenic B cells led to hyporesponsiveness to LPS challenge. This suggests that PBCs may be defective in a signalling pathway, perhaps involving protein kinase C activation.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1992

Direct immunofluorescence testing for immunoglobulin deposits in haired skin, nasal planum and footpads of woodchuck hepatitis virus-infected woodchucks with chronic hepatitis and multiple hepatocellular carcinomas.

The purpose of this study was to determine the frequency of immunoglobulin deposition in the haired skin, footpads, and nasal planums of 10 WHV-infected woodchucks with chronic hepatitis and hepatocellular carcinoma and compare these results with those reported in humans. Immunoglobulin deposition was detected in the skin samples of 3 of 10 woodchucks. Granular deposits were revealed in the superficial dermal blood vessels of the nasal planum, lateral thoracic skin, and footpads in 1 animal each. In 1 of these animals, (lateral thorax) immunoglobulin deposition was concurrently present at the basement membrane zone.

Animals↗
PubMed1992

Bacteria and yeast on the surface and within non-inflamed hair follicles of skin biopsies from cats with non-neoplastic dermatoses.

Coccoid bacteria and/or yeasts were found in the surface keratin or exudate or, rarely, the pilar canal of non-inflamed hair follicles upon light microscopic examination of skin biopsies from 57 of 338 cats (16.9%) with non-neoplastic skin disorders. The presence of these microorganisms did not appear to suggest a specific dermatosis, nor the existence of a clinically relevant infection in the majority of cases.

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PubMed1992

Bacteria and yeast on the surface and within non-inflamed hair follicles of skin biopsies from dogs with non-neoplastic dermatoses.

Coccoid bacteria and/or yeasts were found in the surface keratin or exudate and/or in the pilar canal of non-inflamed hair follicles upon light microscopic examination of skin biopsies from 191 of 3,387 dogs (5.6%) with non-neoplastic skin disorders. The presence of surface cocci and/or yeast did not appear to suggest a specific dermatosis, nor the existence of a clinically relevant infection in the majority of cases. However, follicular cocci and/or yeast almost always indicated the presence of a clinically relevant infection.

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PubMed1992

Microscopic anatomy of the skin of the woodchuck (Marmota monax): comparison of woodchuck hepatitis virus-infected and non-infected animals.

Thirty-three woodchucks were used in this study. Seventeen animals were healthy adults, not infected with woodchuck hepatitis virus (WHV); 10 were healthy adults infected with WHV; 4 were noninfected neonates; 2 were infected neonates. Within the 4 groups of woodchucks, no histologic differences were detected on the basis of sex or age. Neither were histologic findings different between infected and noninfected woodchucks of similar ages. The average thickness of skin (as measured from the skin surface to the inner limit of the dermis) from the general haired body area was 2394 microns. The skin was thickest on dorsal body areas, and gradually became thinner on ventral body and medial limb areas. The epidermis consisted of 4 layers: stratum basale, stratum spinosum, stratum granulosum, and stratum corneum. A stratum lucidum was present only in the epidermis of the footpads. There was no clear distinction between the superficial dermis and the deep dermis, except for the subtle differences in arrangement and size of collagen fibers. Elastic fibers were seen throughout the dermis, being more prominent in the superficial portion. Both compound and simple hair follicle arrangements were seen, with compound being more common. The arrectores pilorum muscles were largest in the skin over the dorsal body areas. Sebaceous glands were present either within the outer root sheath of hair follicles or in the dense connective tissue surrounding hair follicles. No apocrine sweat glands were found. However, there were abundant eccrine sweat glands in the subcutaneous fat of the footpads.

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PubMed1992

Skin disorders of the laboratory woodchuck (Marmota monax): a retrospective study of 113 cases (1980-1990).

An 11-year retrospective study was conducted on the dermatoses occurring in 113 woodchucks from a colony at the College of Veterinary Medicine at Cornell University. Bacterial dermatitis was the most common dermatologic disorder, accounting for 70.2% of the cases. The highest incidence of bacterial dermatitis occurred in September/October prior to hibernation and in February/March during the breeding season. Other dermatoses observed during the study period included Taenia crassiceps infection, microfilarial dermatitis, telogen defluxion, various neoplastic and hyperplastic lesions, and various neonatal conditions associated with trauma and/or bacterial infection. No association was found between any of these dermatoses and the presence of woodchuck hepatitis virus infection.

Alopecia↗
PubMed1992

Prevention of B cell clonal deletion and anergy by activated T cells and their lymphokines.

B cell tolerance is described as the absence of a measurable antibody forming response to an antigenic challenge. The establishment of antigen-specific tolerance requires, by definition, engagement of the B cell antigen-specific receptor. However, only in some circumstances does this engagement lead to tolerance, while in others it produces B cell activation and secretion of immunoglobulins. Several mechanisms occur naturally in vivo abrogating the expression of deleterious autoantibodies and contributing to the state of self-tolerance. In this review, we will examine different ways in which B cell tolerance can be broken, focusing on evidence showing that activated-T cells and/or their lymphokines can prevent B cell clonal deletion and thus have a potential role in the pathogenesis of autoimmune diseases. This approach is based on the well-known association of several lymphokines, such as IL-1, IL-2, IL-4, IL-5, and type I interferons, with autoimmune phenomena in vivo.

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PubMed1992

Anti-immunoglobulin treatment of murine B-cell lymphomas induces active transforming growth factor beta but pRB hypophosphorylation is transforming growth factor beta independent.

Cross-linking of B-cell membrane immunoglobulin (Ig) receptors induces growth arrest at G1-S, leading to apoptosis and cell death in the immature lymphomas WEHI-231 and CH31, but not in the CH12 B-cell line. In this system, which has been used as a model for B-cell tolerance, we have established that these lymphomas produce active transforming growth factor beta (TGF-beta) when treated with anti-Ig and that their hierarchy of sensitivity to TGF-beta generally correlates with their growth inhibition by anti-Ig. TGF-beta, in turn, has been shown to interfere with the phosphorylation of the retinoblastoma gene product, pRB. Herein, we also demonstrate that in WEHI-231 B-lymphoma cells treated with anti-Ig for 24 h, the pRB protein is found to be predominantly in the underphosphorylated form, as previously reported for cells arrested by the exogenous addition of TGF-beta. However, neutralizing antibodies to TGF-beta failed to prevent growth inhibition by anti-Ig in WEHI-231 and CH31. When WEHI-231 lymphoma cells were selected for growth in TGF-beta, the majority of the TGF-beta-resistant clones remained sensitive to anti-Ig-mediated growth inhibition. In these clones, the retinoblastoma gene product was found to be in the underphosphorylated form after 24-h treatment with anti-Ig, but not with TGF-beta. These data show that anti-Ig treatment of murine B-cell lymphomas stimulates the production of active TGF-beta but that a TGF-beta-independent pathway may be responsible for the pRB underphosphorylation and cell cycle blockade.

Animals↗
PubMed1992

Comparison of the clinical efficacy of two commercial fatty acid supplements (EfaVet and DVM Derm Caps), evening primrose oil, and cold water marine fish oil in the management of allergic pruritus in dogs: a double-blinded study.

Twenty dogs with atopy or idiopathic pruritus were treated in a double-blinded clinical trial with computer-randomized and computer-generated sequences of 4 fatty acid-containing products: evening primrose oil, cold water marine fish oil, DVM Derm Caps, and EfaVet. Each dog received each product for a 2-week period. Five of 20 dogs (25%) had a good-to-excellent reduction in their level of pruritus with at least 1 of the products: evening primrose oil (2 dogs), DVM Derm Caps (1), EfaVet (1), DVM Derm Caps and cold water marine fish oil (1). Only 1 dog experienced a side effect (loose stools). Clinical response to fatty acid supplements appeared to be quite individualized, and independent of age, breed, sex, weight, duration of disease, specific diagnosis, or number of positive intradermal test reactions.

Animals↗
PubMed1992

Nonsteroidal management of canine pruritus with amitriptyline.

Thirty-one dogs with nonlesional pruritus were treated with amitriptyline (1 mg/kg orally q12h) to determine its efficacy in the management of canine allergic pruritus. Seventeen dogs were known to be atopic, 8 were presumed to be atopic, and 6 had pruritus of undetermined etiology. Pruritus was virtually eliminated in 5 (16.1%) dogs, reduced by approximately 50% in another 5 (16.1%) dogs, and not changed in the remaining 21 dogs. Side effects were uncommon.

Amitriptyline↗
PubMed1991

A polyclonal model for B cell tolerance. I. Fc-dependent and Fc-independent induction of nonresponsiveness by pretreatment of normal splenic B cells with anti-Ig.

We have developed a simple and adaptable, polyclonal model for B cell nonresponsiveness that is based on the inhibitory activity of anti-Ig as a surrogate for Ag. In our system the induction phase (treatment with anti-Ig) is separated from the challenge phase (Ag or mitogen), so that the critical events in each phase can be evaluated. Our results show that T cell-depleted B cells precultured for 18 to 24 h with rabbit anti-Ig reagents are rendered unresponsive to challenge with either Ag, fluorescein coupled to Brucella abortus (FL-BA), or mitogen (LPS). This state of nonresponsiveness (anergy) is reflected by an inhibition of a prototype response to the fluorescein hapten, as well as total Ig and IgG synthesis, but no reduction in proliferation to LPS. Interestingly, mitogen-induced polyclonal antibody formation was consistently reduced by 90% by treatment with either F(ab')2 or intact IgG anti-Ig. In contrast, the Ag-driven (FL-BA) response of pretreated B cells was inhibited by only 50 to 70%. Moreover, the latter effect usually required pretreatment with intact IgG anti-Ig, a result that suggests the importance of an Fc-dependent negative signal affecting the B cell's response to FL-BA. Furthermore, pretreatment and coculture of B cells with IL-4 blocked the Fc-dependent inhibition of the FL-BA responsiveness. These results, as well as kinetics experiments establishing a 4-h latent period, suggest that simple blocking of surface Ig receptor on target B cells is not responsible for the induction of anergy. Pretreated B cells displayed unique phenotypic changes after treatment with anti-Ig, including a diminution of Thy-1 expression in response to LPS + IL-4, as well as a reduction in membrane IgM and J11d expression (i.e., they were IgMlo, IgDmed, and J11dlo, as recently reported for anergic B cells in transgenic mice). These results suggest that B cell anergy can be induced in mature B cells by both Fc-dependent and Fc-independent processes that lead to unique phenotypic changes and may reflect egress from G0 in the absence of T cell help. The significance of these changes to tolerance mechanisms is discussed.

Animals↗
PubMed1991

A polyclonal model for B-cell tolerance. II. Linkage between signaling of B-cell egress from G0, class II upregulation and unresponsiveness.

Overnight exposure of adult splenic B cells to anti-Ig, a surrogate for antigen/tolerogen, can result in a hyporesponsive state in terms of antibody synthesis. Since B cells treated with either intact of F(ab')2 fragments of anti-Ig will exit the G0 phase of the cell cycle and enter G1 or S, respectively, we examined which steps in B-cell activation were required for this form of hyporesponsiveness. We found that B-cell hyporesponsiveness could be induced under conditions leading to either abortive or productive B-cell cycle progression, depending on the immunogenic challenge employed. Thus, PMA + ionomycin, concanavalin A, PMA alone, or ionomycin alone induced hyporesponsiveness. Each of these reagents is able to drive B-cell exit from G0 into G1 and cause class II hyperexpression. We next examined the effect of cyclosporin A (CSA), a reagent that blocks anti-Ig but not by PMA-induced class II hyperexpression. Interestingly, CSA only interfered with the induction of B-cell hyporesponsiveness with anti-Ig. These results suggest that upregulation of MHC class II may be coincident with a CSA-sensitive tolerance pathway in B cells stimulated by anti-Ig. Finally, IL-4 pretreatment was found to ablate hyporesponsiveness induced by either intact anti-Ig or PMA. These results parallel the Fc-dependent induction of hyporesponsiveness reported earlier (G. Warner and D. W. Scott, J. Immunol. 146, 2185, 1991). We propose that crosslinking of surface Ig, leading to cell cycle progression out of G0 as well as class II hyperexpression, in the absence of a cognate T cell signal, leads to B-cell hyporesponsiveness.

Animals↗
PubMed1991

Lymphoma models for B-cell activation and tolerance. IX. Efficient reversal of anti-Ig-mediated growth inhibition by an activated TH2 clone.

We have utilized several B-cell lymphomas that are growth inhibited by anti-Ig reagents as models for tolerance induction. In a previous communication, we demonstrated that the growth inhibition by anti-Ig can be partially prevented by the recombinant lymphokine, IL-4. In this paper, we report that complete protection of B lymphomas from anti-Ig was provided by a type 2 helper cell clone, D10.G4, when these T cells were activated by monoclonal anti-CD3. Conditioned medium from anti-CD3-stimulated D10.G4 cells also provided protection from anti-Ig. In contrast, little protection was observed with activated cells from a type 1 T-cell clone, A.E7. Furthermore, we show that combinations of IL-4 and tumor necrosis factors (both TNF alpha and TNF beta), as well as IL-4, effected partial protection by themselves and enhanced the activity of the other lymphokine if used in a pretreatment protocol. However, anti-cytokine antibodies were ineffective at reversing the T-cell-mediated protection. The possibility that direct T:B-cell contact mediates part of the protective signal is discussed.

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PubMed1991

Cutaneous trichilemmal cysts in three dogs.

Cutaneous trichilemmal cysts were recognized in 3 dogs. The lesions were multiple, asymptomatic, and occurred over the dorsal lumbar, lateral thoracic, dorsal neck, and cranial carpal regions. These cysts were not accompanied by other disease processes, and did not recur following surgical excision. Histologically, the trichilemmal cyst is characterized by trichilemmal differentiation of the entire cyst wall, and the formation of a predominantly amorphous and nonlaminated keratin in the cyst cavity.

Animals↗
PubMed1991

A clinical study on the efficacy of two commercial veterinary emollients (MicroPearls and Humilac) in the management of wintertime dry skin in dogs.

Twenty dogs with wintertime dry skin were treated with 2 commercial veterinary emollients. All dogs received weekly treatment for 4 weeks according to manufacturers' recommendations. In one-half of the dogs, treatment was initiated with MicroPearls (2 weeks) and followed with Humilac (2 weeks). This sequence was reversed for the other one-half of the dogs. MicroPearls was the superior product in 16 of the 20 dogs (80%). Side effects were rare with either product.

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