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Biomedical subjects

D W Scott

Publications and source records attributed to D W Scott.

At least 235 records · Page 13Linked to original sources

Nodular skin disease associated with Dirofilaria immitis infection in the dog.

Three dogs with dirofilariasis had a dermatologic syndrome, characterized by pruritus and multifocal nodules which tended to ulcerate. The cutaneous nodules revealed angiocentric pyogranulomatous inflammation with variable numbers of eosinophils. Microfilariae were often present in the blood vessels surrounded by the pyogranulomatous process. Therapy for dirofilariasis resulted in complete resolution of the dermatitis.

Animals↗

Functional differentiation of T cell precursors. I. Parameters of carrier-specific tolerance in murine helper T cell precursors.

Irradiated mice reconstituted with bone marrow from sheep gamma-globulin- (SGG) tolerant syngeneic donors display reduced IgG responsiveness to challenge with trinitrophenylated (TNP)-SGG compared with recipients of normal marrow. This effect is SGG-specific and is due neither to suppressor T cells nor to antigen carryover. "Helper T cell precursor tolerance" can be induced with as little as 40 micrograms tolerogen (SGG). Unlike mature helper T cells, these precursors show both a rapid induction and rapid waning patterns, suggesting a high rate of turnover. Our results imply that marrow helper T cell precursors bear antigen-specific receptors and that the T cell repertoire must be at least partially generated before residence in the thymus.

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B-cell subsets responsive to fluorescein-conjugated antigens. III. Differential effect of E. Coli lipopolysaccharide on T-dependent and T-independent responses in vivo.

The effect of E. coli lipopolysaccharide (LPS) on the induction of both hapten-specific immunity and tolerance was studied in an in vivo system utilizing putative T-cell dependent (TD) or T-cell independent (TI) challenge antigens. The administration of LPS 1 day prior to challenge preempted the response of C3D2 mice to a TD antigen (FL-KLH) but had little effect on the response to FL-Ficoll, a TI antigen. LPS did not affect the responsiveness of C3H/HeJ mice, an LPS-unresponsive strain, to either antigen. The reduction of the response to a putative T-dependent antigen by LPS pre-treatment was only temporary since mice challenged 7 days after LPS responded normally in vivo. We also confirmed that LPS administered shortly after a tolerogen prevented FL-specific IgG tolerence induction and produced B-cell priming to a subsequent T-dependent antigenic challenge. LPS, however, did not significantly interfere with tolerance induction in terms of the IgM responce to either challenge antigen. These results suggest that LPS acts either directly or indirectly on a subpopulation of B cells responsive to a TD antigen. Our data further reflect the heterogeneity of B-cell subpopulations responsive to various polyclonal activators.

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Role of IgD in the immune response and tolerance. II. Precursor analysis of murine B cells separated on the basis of surface IgD or treated with an anti-delta serum.

Precursor analysis of the function of murine B cells with surface IgD has been accomplished using an alloantiserum directed against a delta allotype and cellular affinity chromatography. Spleen cells from 3-week-old C57BL.Ige mice were treated with a TNP-labeled anti-delta allotype serum, washed and passed through an anti-TNP affinity column. The cells passing such a column were depleted of IgD-bearing lymphocytes by immunofluorescence and also showed a greatly reduced ability to develop into specific antibody-forming cell clones vs. the fluorescein (FL) hapten in a limiting dilution microculture system in vitro. In contrast, the IgD-bearing cells eluted from such columns were slightly enriched in precursor activity compared to the original population. Moreover, brief treatment with anti-delta serum alone produced a partial reduction in the precursor frequency vs. FL with C57BL.Ige spleen cells (which bear the appropriate delta allotype) but not C57BL/6 spleen cells (which are negative for this delta allotype). This effect varied with the age of the spleen donor, but was most dramatic with splenocytes from 2 to 3-week-old mice. This contrasts with the effect of anti-mu pretreatment, which only inhibited neonatal precursors. The results are interpreted in terms of the maturation of murine B cells and the function of IgD and IgM receptors in triggering an immune response.

Aging↗

Surface immunoglobulin phenotype of murine spleen cells which form B cell colonies in agar.

Separation of IgD-bearing B lymphocytes from the spleens of 3-week-old or adult mice has been achieved using cellular affinity columns and an anti-delta allotype serum. The results demonstrate that the majority of cells capable of forming B lymphocyte colonies in agar are delta-positive although they lose detectable IgD upon stimulation. It is proposed that these cells are the descendants of IgD-negative cells found in the fetal liver and neonatal spleen.

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The anti-delta suppressed mouse.

The ontogeny of IgD was examined in neonatal to adult mice by immunofluorescence. The first delta-positive cells appeared in the spleen at about 3 days of age, while lymph nodes from 4 to 5-day-old mice already contained 10--20% delta-positive B cells. In order to study the function of IgD, we developed a system in which the appearance of delta-positive cells was suppressed by treatment of mice from birth with an anti-delta allotype serum. Immunofluorescence studies showed that very few delta-positive cells could be found in the spleen and lymph nodes of such suppressed mice, and also that the percentage of mu-positive cells was reduced by about 50%. The recovery from suppression was rapid, indicating that potential delta-positive cells were modulated rather than killed. Studies of the immune response of suppressed mice in vitro and in vivo showed that suppression had little effect on the IgM response but caused a definite reduction in the IgG response.

Aging↗

Case report: benign liver tumor with central necrosis.

A 38 year old previously well woman had sudden onset of upper abdominal pain and fever. Ultrasound examination revealed a necrotizing lesion in the liver. Arteriography revealed findings consistent with an adenoma or focal nodular hyperplasia. A right lobectomy and wedge resection of a similar lesion in the left lobe were done. Microscopy of both lesions indicated focal nodular hyperplasia. Adenoma is said to be related to the contraceptive oral hormone; focal nodular hyperplasia not. But it is possible that both may have an increased incidence of bleeding in the users of the oral contraceptive hormones.

Adenoma↗

Predicting the response time of an urban ambulance system.

Response time, i.e., the time from dispatch of an ambulance to its arrival at the scene of an emergency, is an important measure of performance in an urban ambulance system. We developed a model that predicts the entire distribution of response time, explicitly accounting for the rate and spatial distribution of demand, variable ambulance velocities, and queueing effects. We tested the model using data sampled from 3,936 ambulance runs in Houston and achieved close agreement between empirical and predicted distributions of response time. Our use of probability theory to predict response times yielded a model that complements those previously reported for planning and evaluating urban ambulance systems.

Ambulances↗

Role of IgD in the immune response and tolerance. I. Anti-delta pretreatment facilitates tolerance induction in adult B cells in vitro.

Adult spleen cells from C57BL.Ige mice, which generally are resistant to in vitro tolerance induction in the B-cell compartment, became hyporesponsive (tolerant) when cultured with antigen in the presence of an anti-allotype serum. Both antigen and anti-delta had to be present for this effect, which was hapten-specific and did not occur in C57BL/L mice, which lack the Ig5-1 allotype of the delta-chain detected in this system. Preculture with anti-mu serum plus antigen, in contrast, did not cause tolerance induction in adult spleen B cells of either strain. These results suggest that the surface IgD may act as a failsafe receptor to prevent tolerance induction in adult B cells. Tolerance studies with spleen cells from mice with markedly reduced numbers of IgD+ve cells, because of regimen of repeated injections of anti-delta serum beginning at birth (delta-suppressed mice), confirmed the importance of membrane IgD in preventing tolerance, because such delta-suppressed mice were hypersusceptible to tolerance by antigen alone. Inasmuch as immature B cells lack IgD on their surface, these studies suggest that acquisition of IgD is an important maturational step in the ability of murine B cells to discriminate tolerogenic and immunogenic signals.

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Epidermolysis bullosa simplex in the Collie dog.

Epidermolysis bullosa simplex was diagnosed in 4 Collie dogs. Three of the dogs were less than 6 months old when lesions were first noticed. Lesions were characterized by alopecia, erythema, edema, erythematous plaques, erosions, ulcers, crusts, atrophy, pigmentary changes, and (rarely) blisters affecting the skin over bony prominences and joints of the limbs, face, lips, and ears. Minimal to moderate pruritus or pain was manifested by chewing and licking at the affected areas of the limbs and by pawing and rubbing at the face and ears. Lesions could be induced by frictional trauma in areas of normal skin. Diagnosis was confirmed by histologic examination of affected tissues and induced lesions. Therapy with large oral doses of prednisolone and avoidance of trauma were palliative.

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Role of self-carriers in the immune response and tolerance. II. Parameters of tolerance induced by haptenated lymphoid cells.

The induction of tolerance to the 2,4,6-trinitrophenyl (TNP) hapten has been studied in a system utilizing haptenated syngeneic lymphoid cells. Specific depression of the direct and indirect plaque-forming cell (PFC) responses to TNP-protein conjugates was regularly achieved by pretreatment of Lewis rats with 1 X 10(7) trinitrophenylated spleen cells or TNP lymph node cells. Very low numbers of haptenated lymphocytes were active since tolerance could be induced in vivo with as few as 10(5)-10(6) TNP spleen cells (SC). SC exposed to as little as 10-100 mug of the reactive hapten, trinitrobenzene sulfonic acid, were effective tolerogens in this system. Tolerance induced with 10(7) haptenated spleen cells persisted for at least 4 weeks. Viable intact cells did not seem to be required in this system since the cell-free supernatants from TNP-SC cultured for 24 h were also active. In addition, significant depression of an ongoing immune response could also be imposed by haptenated isologous lymphoid cells. Moderate suppression of the "hapten-specific" delayed hypersensitivity response (measured by the accumulation of 51Cr-labeled bone marrow cells) was also achieved with TNP-SC. These results suggest that haptenated isologous lymphoid cells are potent tolerogenic conjugates capable of inducing tolerance affecting antibody formation and delayed hypersensitivity. However, since we and others have shown that TNP-SC do not adversely affect the generation of hapten-specific cytotoxic T cells, it is postulated that there is a differential recognition of, or response to, hapten-modified self-carriers by functionally distinct lymphocyte subpopulations.

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