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Biomedical subjects

D W Scott

Publications and source records attributed to D W Scott.

At least 127 records · Page 7Linked to original sources

Human brainstem auditory evoked potentials fail to provide evidence of efferent modulation of auditory input during attentional tasks.

Efferent modulation of auditory input at the level of the brainstem during attention-demanding tasks has been described in animal studies. Attempts to demonstrate these effects in humans have produced conflicting results, however. These studies are reviewed with particular reference to those animal experiments that have demonstrated peripheral effects. The human experiments have used a number of attentional conditions which have not been related either to each other or to the successful animal work. Two of the most important conditions in these studies--the use of an intermodal attention task and the manipulation of attentional states--have been examined rarely or not at all in the human research. Two experiments were conducted to investigate the possibility of attention-related effects on the human brainstem auditory evoked potential. These experiments were designed to examine experimental conditions common to both successful and unsuccessful attempts to demonstrate attention-driven efferent modulation at the periphery in humans. Also examined was the gradation of attention effects on efferent modulation demonstrated in animals but never studied in humans. No significant changes in either the latency or the amplitude of the brainstem auditory evoked potential were found in any of the attention-demanding conditions. Results are discussed in terms of psychophysiological theories of attention. Also, the interpretation of the most recent animal work is questioned.

Adolescent↗

Presumptive subcutaneous surgical transplantation of a urinary bladder transitional cell carcinoma in a dog.

A urinary bladder mass in a 12-year-old spayed female West Highland White Terrier was diagnosed after exploratory surgery and biopsy as a transitional cell carcinoma. Four months later the dog presented with an ulcerated plaque-like cutaneous lesion at the previous surgical incision site; concurrent inguinal lymphadenopathy and recurrence of the urinary bladder mass were identified. Transitional cell carcinoma was diagnosed at all 3 sites. Although a definitive relationship cannot be established between the initial surgery for urinary bladder mass and the resultant subcutaneous lesion, surgical implantation should be considered as a source for the neoplastic cells.

Animals↗

Lymphoid nodules in skin biopsies from dogs, cats, and horses with nonneoplastic dermatoses.

In a retrospective histopathologic study of nonneoplastic dermatoses, lymphoid nodules were found in 0.3% of 3,408 canine, 5.1% of 469 feline, and 4.5% of 325 equine skin biopsies. In all 3 species, the majority of cases wherein lymphoid nodules were found were diseases of presumed immune-mediated nature. In cats and horses, the majority of cases were also diseases characterized by tissue eosinophilia.

Animals↗

Idiopathic benign lichenoid keratosis on the pinna of the ear in four dogs.

Histologically, multiple wart-like papules or hyperkeratotic plaques on the ear pinnae from 4 dogs were characterized as idiopathic benign lichenoid keratosis. Common histologic features included a discrete lesion of irregular and papillated epidermal hyperplasia with a moderate diffuse lichenoid interface inflammatory infiltrate consisting of lymphocytes and plasma cells. There was also focal hydropic degeneration of the epidermal basal cell layer, pigmentary incontinence, and mixed orthokeratotic and parakeratotic hyperkeratosis. In all 4 dogs, the pinnal lesions were unilateral and asymptomatic. Complete surgical excision was curative.

Animals↗

Activation events in hapten-specific B cells from tolerant mice.

We have studied hapten-binding cells from the spleens of normal and tolerant adult mice in terms of their ability to enlarge, proliferate, and differentiate into antibody-secreting cells. Tolerant B cells showed clear defects in intermediate activation events in addition to a deficit in antibody-secreting cells. In these studies, isolated B cells were stimulated by T cell independent Ag with lymphokines, or with mitogens, in the absence of filler cells. The number of antibody-secreting cells generated from the tolerant population was consistently reduced by 70 to 80% of the control response to the specific Ag, fluoresceinated Brucella abortus (FL-BrA) +/- lymphokines. We found that similar numbers of normal and tolerant cells enlarged (entered cell cycle) when stimulated by FL-BrA, LPS, IL-4, or alpha-Ig coupled to dextran (alpha-Ig-dex). Ia induction stimulated by IL-4, LPS, FL-BrA, or alpha-Ig-dex was the same in normal and tolerant cells. However, DNA synthesis stimulated by FL-BrA, FL-BrA + IL-5, or suboptimal concentrations of LPS was reduced by 70% in the tolerant cell population. Proliferation in response to 50 micrograms/ml LPS or to low doses of alpha-Ig-dex was similar in normal and tolerant B cells. These data suggest that the primary defect in adult B cell tolerance is the ability to proliferate in response to Ag.

Animals↗

Postdischarge distress in surgically treated cancer patients and their spouses.

Temporal patterns of distress among two groups of nonterminally ill, surgically treated cancer patients (n = 40) and their spouses (n = 40) during the immediate pre- and postdischarge period were studied. Data about problems encountered and standardized measures of distress (State Anxiety Index, Brief Symptom Index, and Vulnerability Index) were obtained before hospital discharge and at 10, 30, 60, 90, and 180 days postdischarge. The intensity of distress experienced by patients and spouses was remarkably similar, although the temporal pattern of occurrence was significantly different. Prior to discharge, spouse anxiety was significantly higher than that of the patients and above the norm for hospitalized persons. Spouses were least distressed after 10 days at home, but thereafter experienced a rise in vulnerability culminating in observable clinical depression at 90 and 180 days. Peak distress for the patients occurred 10 days after discharge as a function of physical symptoms that were unexpected or more severe than anticipated. Patients with ostomies (n = 20) were slower to return to pre-illness functional levels and had somewhat more psychological distress than nonostomy patients.

Depression↗

Lymphoma models for B-cell activation and tolerance. VII. Pathways in anti-Ig-mediated growth inhibition and its reversal.

WEHI-231, CH33, and CH31 are B-cell lymphomas that are inhibited in their growth by crosslinking of surface Ig receptors during early G1. This "negative signaling" process can be prevented or reversed under certain conditions. In the present paper, we use a cell synchronization procedure to demonstrate that activation of protein kinase C (PKC) is not involved in the negative signal for growth, but rather that PKC activation prevents growth inhibition when present early in the cell cycle. Indeed, the prevention of negative signaling is only accomplished by active phorbol esters. Moreover, phorbol esters and a calcium ionophore fail to deliver a negative signal under conditions in which anti-Ig can significantly prevent cell cycle progression into S phase, thereby ruling out synergy between PKC and calcium in growth inhibition. Whether phorbol esters reverse negative signaling by preventing internalization of the immune complex or phosphorylation of a critical intracellular protein is discussed.

Animals↗

Role of self carriers in the immune response and tolerance. XI. Correlation of Ia expression and interleukin-1 production with delivery of immunogenic signals in vivo by hapten-modified accessory cell-like tumor lines.

It was recently demonstrated that a lymphoid dendritic-like tumor, P388AD.2, presented hapten-modified self (HMS) in an immunogenic fashion even after injection via the normally "tolerogenic" intravenous (iv) route. To determine whether this property was unique to the P388AD.2 line, other hapten-modified tumors were administered iv and the result of their presentation was measured by changes in the number of splenic plaque-forming cells (PFC) following in vitro challenge with thymic-independent antigens. Of the six tumors tested, two (P388 and J774.5R) primed for augmented PFC responses, while four others (P388NA.10, P388D1, WEHI-231, and 70Z/3) did not. When these tumors were compared for Ia expression and production of interleukin-1 (IL-1), it was discovered that (1) all of the immunogenic tumors were Ia+ and IL-1 producing (IL-1+), although not all Ia+,IL-1+ tumors could elicit augmented PFC responses; (2) none of the tumors that were deficient in either Ia expression or IL-1 production could prime B-cell responses in vivo; and (3) the ability to augment PFC responses was proportional to the density of Ia on the immunogenic tumors. These results demonstrated that P388AD.2 was not the only tumor line capable of presenting HMS iv as an immunogen, and that the accessory cell phenotype is critical for the induction of an immunogenic response in vivo.

Animals↗

Role of self carriers in the immune response and tolerance. XII. Effect of epitope density and antigen-presenting cell phenotype on the presentation of hapten-modified self for the induction of immunity or tolerance in vitro.

The data presented in the accompanying paper (J. P. Cogswell, R. P. Phipps, and D. W. Scott, Cell. Immunol. 114, 55-70, 1988) indicate that certain macrophage-like and lymphoid dendritic-like (P388AD.2) tumor lines which express major histocompatibility encoded class II (Ia) antigens and produce interleukin 1 (IL-1) are uniquely able to present hapten-modified self (HMS) in an immunogenic fashion in vivo. In the current study, the relationship between phenotype and function has been confirmed utilizing a completely in vitro system. This investigation revealed that B-cell priming required T cells restricted to P388AD.2's I-A antigens. In addition, exogenous IL-1 reconstituted the response of an IL-1-deficient tumor (P388AD.2-ILd), although it had no effect on the other nonimmunogenic Ia+ tumor lines. Unlike the in vivo system, effective B-cell tolerance was induced when P388AD.2 was modified with high concentrations (10 mM) of hapten or when highly haptenated tumor was added to 0.1 mM TNBS-modified P388AD.2. These results suggest that positive regulation of in vitro immune responses to HMS is dependent upon the phenotype of the accessory cell carrier (with lymphoid dendritic-like cells being unusually potent), while negative regulation is associated with high epitope density. This system now allows the dissection of the properties of different accessory cells and the signals required for B-cell priming or tolerance induction.

Animals↗

Immunoglobulins D and M mediate signals that are qualitatively different in B cells with an immature phenotype.

The CH family of murine B-cell lymphomas includes several members that are sensitive to growth inhibition when their membrane IgM (mIgM) receptors are cross-linked by anti-mu chain, anti-kappa chain, or anti-idiotypic antibodies. These lymphomas are IgM+, Ia+, and IgD +/- and resemble neonatal B cells in terms of their exquisite sensitivity to anti-IgM-mediated negative signaling as a model for tolerance induction. In this report, we describe the properties of one of these lymphomas, CH33, which had been transfected with a construct containing an allotypically different delta chain constant region and the heavy chain variable region fragment from S107 (T15 idiotype positive). This transfected cell line allowed us to investigate the possibility that membrane IgD (mIgD) and mIgM can mediate different signals. Our results show that the transfected cells retained their exquisite sensitivity to anti-IgM-mediated growth inhibition; however, crosslinking of IgD with anti-delta chain antibody did not inhibit their growth. Furthermore, even prolonged pretreatment with anti-IgD antibodies did not affect cell growth nor did it modulate the inhibitory effects of anti-IgM antibody. Moreover, identical results were obtained with clones of CH33 that express significant amounts of endogenous IgD. Thus, the failure of mIgD to deliver a negative signal does not reflect a defect in the transfected IgD but appears to be a general property of IgD in these cells. The mIgD was shown to mediate transmembrane signals because anti-delta chain treatment resulted in Ca2+ mobilization in transfected CH33 cells and capping of those receptors. We conclude that mIgD can mediate qualitatively different signals than mIgM can and that mIgD expression per se is not sufficient to change the functional phenotype of immature B cells.

Animals↗

Hepatozoon canis in a dog with oral pyogranulomas and neurologic disease.

A ten-month-old Cocker Spaniel presented for fever, difficulty walking, and oral lesions. Muscle pain, bloody diarrhea, respiratory disease and central nervous system inflammation were found while the animal was hospitalized. Merozoites of Hepatozoon canis were discovered in association with pyogranulomas in a muscle biopsy. No other etiologic agent for the clinical signs was identified.

Animals↗

Calcinosis circumscripta of the tongue in a cat.

A nodular mass present on the ventral surface of the tongue in a mature, castrated male domestic short-haired cat was diagnosed as calcinosis circumscripta. The cat died of end-stage renal disease. Histologically, the multilobulated mass was composed of acellular, fractured loculi separated by thin bands of a connective tissue stroma. Loculi contained a light red crystalline substance, surrounded by amorphous basophilic mineralized material. No specific relationship is suggested between the end-stage renal disease and the tongue lesion.

Animals↗