Effect of a multidisciplinary clinic on survival in amyotrophic lateral sclerosis.
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Biomedical subjects
Publications and source records attributed to J Redmond.
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Studies on the immunoglobulin (Ig)E immune responses to the gastric nematode, Teladorsagia circumcincta, have demonstrated a major high molecular weight allergen (HMWTc). Cross reactive allergens of similar MW were demonstrated for Trichostrongylus colubriformis and Cooperia curticei, but not for Haemonchus contortus. Purification of HMWTc was achieved by gel-filtration chromatography, and nonreducing SDS-PAGE and Western blot analysis revealed two closely associated bands with a molecular weight of approximately 140-150 kDa. Reduction showed four IgE reactive bands of 120, 50, 45 and 30 kDa, and deglycosylation abrogated the immunoreactivity of the 120 and 30 kDa bands. Ultrastructural immunolocalization by electron microscopy revealed that the IgE reactivity was confined to the cuticular surface of the infective (L3) larvae. ELISA studies to determine the IgE anti-HMWTc responses in lambs during their first grazing season, demonstrated significantly higher IgE antibody in lambs with low accumulative faecal egg count (FEC) compared to animals with high accumulative FEC. These studies provide evidence for a protective function of IgE antibody in Teladorsagia infections in lambs.
Cellulose, an abundant, crystalline polysaccharide, is central to plant morphogenesis and to many industries. Chemical and ultrastructural analyses together with map-based cloning indicate that the RSW1 locus of Arabidopsis encodes the catalytic subunit of cellulose synthase. The cloned gene complements the rsw1 mutant whose temperature-sensitive allele is changed in one amino acid. The mutant allele causes a specific reduction in cellulose synthesis, accumulation of noncrystalline beta-1,4-glucan, disassembly of cellulose synthase, and widespread morphological abnormalities. Microfibril crystallization may require proper assembly of the RSW1 gene product into synthase complexes whereas glucan biosynthesis per se does not.
The effects of different doses of filgrastim on yields of CD34+ peripheral blood stem cells were evaluated in patients with breast cancer. 55 were randomized to receive filgrastim 10, 20, 30 or 40 microg/kg/d with more CD34+ cells/kg/apheresis harvested after the three highest dose levels. 35 additional patients were randomized to receive 10 or 30 microg/ kg. The median number of CD34+ cells collected after 10 microg/ kg (n = 31) was 0.7 x 10(6)/kg/apheresis (range 0.1-4.4) as compared to 1.2 (range 0.1-6.8) after 30 microg/kg (n = 32) (P = 0.04). Among patients randomized to 10 v 30 microg/kg, more (50%) achieved > or = 5.0 x 10(6) CD34+ cells/kg and less aphereses were required to achieve > or = 2.5 x 10(6) CD34+ cells/kg after the higher dose (P = 0.04). In multivariate analyses, patients receiving 10 microg/kg (n = 31) had lower yields of CD34+ cells (P = 0.026) and had a 3.3-fold increase in the probability of not achieving > or = 5.0 x 10(6) CD34+ cells/kg as compared to patients receiving 20-40 microg/kg (n = 59). Patients who had received radiation had a 2.9-fold probability of not achieving > or = 2.5 x 10(6) CD34+ cells/kg. These data suggest that, in patients with good marrow reserves, doses of filgrastim > 10 microg/kg/d mobilized more CD34+ cells and may be useful when high numbers of CD34+ cells are desired.
Engraftment kinetics after high-dose chemotherapy (HDC) were evaluated in patients receiving autologous peripheral blood stem cell (PBSC) infusions with a low CD34+ cell content. Forty-eight patients were infused with < 2.5 x 10(6) CD34+ cells/kg; 36 because of poor harvests and 12 because they electively received only a fraction of their harvested cells. A median of 2.12 x 10(6) CD34+ cells/kg (range, 1.17-2.48) were infused following one of seven different HDC regimens. All patients achieved absolute neutrophil counts > or = 0.5 x 10(9)/l at a median of day 11 (range, 9-16). Forty-seven patients achieved platelet counts > or = 20 x 10(9)/l at a median of day 14 (range, 8-250). Nine of 47 (19%) had platelet recovery after day 21, 4/47 (9%) after day 100 and one died on day 240 without platelet recovery. Twenty-six patients (54%) died of progressive disease in 51-762 days; 22 (46%) are alive at a median of 450 days (range, 94-1844), 17 (35%) of whom are surviving disease-free at a median of 494 days (range, 55-1263). No patient died as a direct consequence of low blood cell counts. These data demonstrate that PBSC products containing 1.17-2.48 x 10(6) CD34+ cells/kg resulted in relatively prompt neutrophil recovery in all patients but approximately 10% had delayed platelet recovery.
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Bilateral synchronous testicular cancer is a rare occurrence usually associated with similar histologic findings in each testicle. We describe eight patients with bilateral synchronous testicular germ cell cancer, of whom four had dissimilar histologic findings. Contralateral disease in three patients was identified only by testicular ultrasonography or intraoperative exploration of the contralateral testicle, and in two cases by palpation 6 months after identification of the primary cancer. Treatment was determined by conventional staging and five of eight patients have remained free of recurrent disease.
Acquired pure red cell aplasia (PRCA) has been associated with various lymphoproliferative conditions but its occurrence with Hodgkin's disease is rare. We report a case of PRCA occurring immediately following the completion of induction chemotherapy in a patient with Stage IIIB nodular sclerosing Hodgkin's disease. In vitro erythroid colony studies documented evidence for T cell mediated suppression of erythropoiesis and lack of a serum inhibitor. Addition of cyclosporin to the in vitro cultures stimulated erythroid colony growth. Following in vivo treatment with cyclosporin peripheral blood CD4/CD8 ratios returned to normal. However, serum erythropoietin levels were inappropriately low. Subsequent treatment with erythropoietin induced a reticulocytosis and transfusion independence. Since discontinuing the erythropoietin, the patient has been able to maintain a hemoglobin of 100 g/L. This case illustrates that red cell aplasia occurring in the setting of Hodgkin's disease may be due to T cell mediated suppression of erythropoiesis. A response to cyclosporin may be masked by inappropriately low erythropoietin levels.
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Granulocyte colony-stimulating factor is a glycoprotein that promotes the proliferation and differentiation of neutrophils. It also results in an increase in circulating hematopoietic progenitor cells. We describe two cases of extramedullary hematopoiesis in patients receiving granulocyte colony-stimulating factor with chemotherapy for metastatic breast cancer.
Jeune's syndrome is a rare autosomal disorder characterized by osseous dysplasia, fetal respiratory distress, and renal failure in later life. We describe a 27-year-old man with Jeune's syndrome who underwent renal transplantation and 6 years later developed a sarcoma (primitive neuroectodermal tumor [PNET]) in the soft tissue of the chest wall, a principal site of dysplasia in this disorder.
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Previous work made use of nucleic acid probes corresponding to different subtypes of the class II regions of the human and murine major histocompatibility complex (MHC) to isolate seven different alpha and 24 different beta genes of the ovine MHC from two cosmid libraries. In an attempt to identify pairs of alpha and beta genes capable of cell surface expression, all permutations of alpha and beta genes were in turn transfected into mouse L-cells. Two pairs of alpha and beta genes co-expressed and stable ovine MHC class II L-cell lines were developed. The expressed alpha genes had previously been defined as DR-alpha homologues (DRA) by differential Southern hybridization to human subtype specific class II probes. The expressed ovine beta genes were also assigned as ovine DR-beta homologues (DRB) on the basis of their sequence having a higher degree of similarity with human DRB than any other subtype. A total of eight out of 23 anti-sheep class II specific monoclonal antibodies were typed OLA-DR specific by FACScan analysis using the L-cell lines.
Iron malabsorption compounded the anemia in a patient with diffuse large cell lymphoma involving the small intestine. Both upper gastrointestinal series with small bowel follow-through and computerized tomographic scan demonstrated lymphomatous involvement of the duodenum and proximal jejunum by a retroperitoneal mass. An oral iron-loading absorption test was consistent with malabsorption of iron. After two cycles of systemic chemotherapy, the retroperitoneal mass resolved and the iron loading test normalized.