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Biomedical subjects

W J Smith

Publications and source records attributed to W J Smith.

At least 91 records · Page 5Linked to original sources

Self-report questionnaires in five rheumatic diseases: comparisons of health status constructs and associations with formal education level.

Self-report questionnaire scales to assess various constructs of health status were compared in 602 patients with five rheumatic diseases, including 134 rheumatoid arthritis (RA), 216 osteoarthritis (OA), 84 fibromyalgia, 124 systemic lupus erythematosus (SLE), and 43 scleroderma patients. RA patients showed significantly higher degrees of difficulty, dissatisfaction, and pain in performing eight activities of daily living (ADL) compared to patients with the other four diseases (P less than 0.01), while SLE patients reported the least difficulty, dissatisfaction and pain. Fibromyalgia patients showed significantly higher scores on a visual analog pain scale than patients with the other four diseases (P less than 0.05), followed by OA patients. Fibromyalgia patients reported significantly higher levels of learned helplessness, assessed according to a rheumatology attitudes index (RAI), than patients with all other diseases, and scleroderma patients showed significantly lower RAI scores (P less than 0.05). Patients with all five diseases who had not completed high school showed poorer clinical status than patients who had completed high school on all six scales. Significant differences in questionnaire scores were seen for 24 of 30 comparisons (five diseases and six scales) according to formal education level, versus only two according to age, and none according to duration of disease.

Activities of Daily Living↗

Differences in the flow and absorption cytometric DNA distributions of mouse hepatocytes and tumor cells.

We have determined the DNA content, the ploidy levels, and the percentages of different cell types present in small and large mouse mammary tumors as well as in young and old mouse livers by using absorption and flow cytometry. Absorption cytometry data indicated a significant increase in the proportion of transformed G0/G1 cells in the tumors as compared to that of the stromal G0/G1 cells with progressive tumor growth. This increase was not detected by flow cytometry. In both young and old mouse livers, a small number of cells of higher ploidy (8C and 16C) were detected by absorption cytometry but were not apparent in histograms obtained by flow cytometry. Furthermore, changes in the proportions of liver cells of different ploidy with age were apparent in absorption cytometry data but not in flow cytometry data. In one mouse liver experiment, a 6C cell peak appeared in the flow cytometry histogram, but a direct measurement of DNA content by absorption cytometry failed to detect cells with such a peak. We therefore believe that some caution may be warranted in the use of flow cytometry alone for evaluation of DNA distributions and of the proportions of different types of cells in complex solid tissues.

Animals↗

Mitoxantrone and high-dose ara-C in refractory malignancies: a phase I trial.

On the basis of in vitro studies demonstrating marked synergy between mitoxantrone and high-dose cytosine arabinoside (ara-C) (HiDAC) against L5178Y murine leukemia and clinical studies showing usefulness of the combination in patients with refractory acute myeloid leukemia, a phase I study was initiated to find tolerable doses for use in patients with refractory solid tumors. Initial dose levels were mitoxantrone 2 mg/m2 infused over 30 minutes, followed by high-dose ara-C 750 mg/m2 infused over 3 hours repeated once at 24 hours (total dose 4 mg/m2 mitoxantrone and 1,500 mg/m2 HiDAC per 2-day course), with planned subsequent escalation of mitoxantrone. Moderate-to-severe myelosuppression, however, required sequential dose reduction of both agents. Nonhematologic toxicity was restricted to manageable nausea and vomiting in one-half the patients and a single episode of transient delirium of uncertain etiology. No responses were observed in 23 heavily pretreated patients with a wide variety of malignancies. On the basis of this study, doses of 187-375 mg/m2 ara-C given every 24 hours for two doses following mitoxantrone 1 mg/m2 every 24 hours for two doses would be tolerated by most patients with subsequent dose escalation in some as allowed by myelosuppression.

Adult↗

Fusiform bacterial sepsis. Metastases with osteomyelitis and hepatic abscess occurring in a chaotic family.

Cases of fusiform bacteria sepsis have been reported infrequently in the pediatric literature. This case demonstrates the severe metastatic complications of fusiform bacterial sepsis including osteomyelitis, with multiple pathological fractures, sepsis, and abscesses of the liver. In the diagnostic evaluation of the etiology for this uncommon infection, child abuse was discovered in all children of this family. In children with uncommon infections and no underlying etiology, child abuse should be considered.

Child Abuse↗

Regulation of tension on hair-cell transduction channels: displacement and calcium dependence.

An epithelial preparation of the bullfrog sacculus was used to characterize the initial rate of the adaptation mechanism in hair cells and its dependence on displacement and calcium. The I(X) curve relating transduction current and bundle displacement shifted along the X-axis without substantial change in slope, as previously observed, suggesting that adaptation involves a change in the attachment point of the elastic element connected to ion channels. If the "tip links" model of transduction is correct, this implies that one end of the link moves along the side of the stereocilium. The rates were highly asymmetric: in the tensioning direction the rate was roughly constant at 1-2 microns/sec (calculated as motion along a stereocilium); this is similar to that of myosin on actin. In the relaxing direction it appeared linearly dependent on tension. Calcium preferentially potentiated the relaxation, and apparently reduced the resting tension in the elastic element. The calcium site appears specific for calcium, as other divalent cations inhibited its action. Dihydrostreptomycin inhibited the positive rate, but its effect could not be explained by a simple channel block, and it seems inconsistent with screening of negative charge in the mouth of the transduction channel.

Animals↗

Primary B-cell lymphoma of salivary glands and its relationship to myoepithelial sialadenitis.

A detailed morphologic and immunohistochemical study has been carried out on salivary glands excised from 20 cases in which the initial histologic diagnosis was either myoepithelial sialadenitis (MESA) or salivary gland lymphoma (SGL). The results have shown that these cases, except one that had been diagnosed as MESA, showed a spectrum of changes ranging from focal lymphoid infiltrates, designated as early MESA, through established MESA with dense, extensive lymphoid infiltration, to lymphoma. The distribution of the lymphoid infiltrate in early MESA was related to ducts and mimicked Peyers patches. In established MESA, this infiltrate became confluent with the formation of prominent epimyoepithelial islands. The evolution of lymphoma was characterized by an expanded population of centrocyte-like (CCL) cells that showed light chain restriction. Like other lymphomas of mucosa-associated lymphoid tissue, to which they bear a striking resemblance, salivary gland lymphomas may remain localized for prolonged periods with a tendency to local recurrence rather than to distant spread. These properties may be explained by the histogenesis of these tumors from CCL cells that appear to be of similar lineage of splenic marginal zone cells.

Adult↗

T-cell-rich B-cell lymphoma.

Five cases of B-cell lymphoma are described in which the morphology and initial immunohistochemistry suggested a diagnosis of T-cell neoplasia. In four cases, the histological picture was that of an adult pleomorphic T-cell lymphoma; the fifth case was a lymphocytic lymphoma (CLL) with an accompanying T-cell lymphocytosis in the peripheral blood. Immunohistochemistry on both frozen and paraffin-embedded material showed that the cellular population in all five cases consisted mainly of T-cells; less than 10% of the cells stained as B-cells. However, immunoglobulin immunostaining combined with use of the new lineage-related monoclonal antibodies reactive in paraffin section revealed that the B-cells constituted the neoplastic population. Genetic analysis showed no evidence of clonality in the T-cells, nor was it able to detect rearrangement in the small number of clonal B-cells present. These cases represent a variety of B-cell neoplasia that mimicks T-cell lymphoma morphologically and immunologically. The vigorous T-cell reaction seen in such lymphomas means that the malignant population can be correctly identified only by careful examination of the immunohistochemical findings.

Antibodies, Monoclonal↗

Immunoglobulin gene rearrangement and antigenic profile confirm B cell origin of primary cerebral lymphoma and indicate a mature phenotype.

Six cases of primary cerebral lymphoma were immunophenotyped and analysed by Southern blotting to determine the clonality and lineage of these neoplasms. Molecular analysis showed that they were of B cell origin, and the rearrangement of both heavy and light chain immunoglobulins in malignant cells showed that they were monoclonal populations of mature B cells. The characterisation of the genetic configuration of the immunoglobulin genes in these lymphomas is important because the ability to distinguish between primary lymphoma of the central nervous system and other malignant cerebral tumours has important implications for treatment and survival.

Aged↗

T-cell lymphomas in adults: a clinicopathological study of eighteen cases.

Eighteen cases of adult T-cell lymphoma have been studied with respect to clinical presentation, response to treatment, histology, enzyme histochemistry, immunocytochemistry, and gene rearrangement. Seven cases (39 per cent) presented at extra-nodal sites, and the age range was from 18 to 79. Treatment was with combination chemotherapy in most cases, and 11 of the 18 patients died within the three year follow-up period. The lymphomas were classified morphologically into six types; T-lymphoblastic lymphoma (TLL), angioimmunoblastic lymphadenopathy (AIL)-like T-cell lymphoma, T-zone lymphoma, pleomorphic mixed medium and large cell T-cell lymphoma (PMMLC), pleomorphic large cell T-cell lymphoma (PLC), and monomorphic large cell T-cell lymphoma (MLC). Enzyme histochemistry was found to be of limited value in the identification of T-cell lymphomas. Immunocytochemistry showed a degree of correlation between the immunological profile and morphology, with cases in the PLC and MLC groups showing limited expression of T-cell antigens. Re-arrangement of the beta chain of the T-cell receptor gene was detected in 12 of the 14 cases studied, and all showed germ-line immunoglobulin genes. The study emphasizes the varied morphological and clinical appearances of adult T-cell lymphoma.

Adolescent↗

Immunoglobulin gene rearrangement in immunoproliferative small intestinal disease (IPSID).

Analysis of DNA from the mucosal tissue of three patients with immunoproliferative small intestinal disease (IPSID) and alpha chain disease, two of whom had early stage disease responsive to antibiotics, showed monoclonal heavy and light chain gene rearrangements in all cases. These findings suggest that IPSID is neoplastic even in its early stages, but that the neoplastic cells respond to normal stimuli. Monoclonal lymphoid populations could not be detected in circulating lymphocytes from these patients, which raises the possibility that the circulatory pathways of lymphocytes derived from human gut associated lymphoid tissue may not necessarily parallel those in experimental animals.

Adolescent↗