Hyperviscosity syndrome with transient abnormal myelopoiesis in Down syndrome.
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Biomedical subjects
Publications and source records attributed to M Fukuda.
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In order to assess whether cyclosporine (CsA) affects the endocrine and exocrine pancreas, 105 patient courses comprised of 87 living related donor (LRD) and 18 cadaver donor (CAD) transplants treated with cyclosporine and prednisolone (Pred) were compared with the results of historical controls of 170 LRD and 10 CAD transplants treated with azathioprine (Az) and Pred. All of the recipients were followed for over 6 months after transplantation. There were no differences in age, sex, Broca index, family history, and preoperative evaluation on diabetic dispositions between the two treatment groups. The incidence of diabetes mellitus (DM) requiring insulin therapy was higher in CsA-treated recipients (18/105, 17.1%) than in Az-treated recipients (23/180, 12.8%; P less than 0.05), although both the daily Pred and cumulative doses of methylprednisolone (MP) at the onset of DM were significantly smaller in the CsA group than in the Az group (26.1 +/- 2.2 mg v 41.4 +/- 3.4 mg, P less than 0.01 and 3,086 +/- 626 mg v 7,133 +/- 1,129 mg, P less than 0.01, respectively). Diabetic patients with CsA showed higher levels of blood glucose (401 +/- 46 mg/dL), but lower amounts of urinary glucose (40 +/- 4.3 g/d) compared with patients treated with Az (239 +/- 31 mg/dL, and 61.4 +/- 4.6 g/d, respectively, P less than 0.05). In the CsA group, the onset of DM was related to high CsA plasma trough levels (greater than 350 ng/mL) in 23% of patients. Insulin could be withdrawn within 3 months in six of eight patients who had been converted from CsA to Az.(ABSTRACT TRUNCATED AT 250 WORDS)
Although several lysosomal membrane glycoproteins have been characterized by using specific antibodies, none of the studies so far elucidated the amino acid sequence of a lysosomal membrane glycoprotein. Here we describe cDNA clones encoding for one of the lysosome-associated membrane proteins with apparent Mr approximately equal to 120,000, lamp A. The amino acid sequence based on the fully coded cDNA shows that as many as 18 potential N-glycosylation sites can be found in the total of 385 amino acid residues. The results obtained by endoglycosidase F digestion support the conclusion that this glycoprotein contains 18 N-glycans. These N-glycosylation sites are clustered in two domains; one contains 10 and the other contains 8 N-glycosylation sites. These domains are separated by a (proline-serine)-rich region that has a distinct homology to the IgA hinge structure. The first N-glycosylated domain is elongated to a potential leader peptide toward the NH2-terminal end. The second N-glycosylated domain, on the other hand, is connected to a putative transmembrane portion consisting of hydrophobic amino acids. This segment, in turn, is elongated to a short cytoplasmic segment composed of 11 amino acid residues at the COOH-terminal end.
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Using a cDNA for glycophorin A (MN), we screened 10 unrelated Caucasians using 22 restriction enzymes for RFLPs. A common StuI RFLP was identified and shown to be in marked linkage disequilibrium with both the MN and Ss blood-group antigens in a larger group of unrelated Caucasians. This provides a DNA marker for a locus that has been of major importance in genetic and population studies. The demonstrated disequilibrium will prove useful in localizing the gene for glycophorin B and in studies of genetic and physical distances on human chromosomes.
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The significance of the minimal secretory capacity of pancreatic beta-cells for the stability of the plasma glucose level was studied in 20 patients with insulin-dependent diabetes mellitus. Changes in plasma concentrations of major counterregulatory hormones in response to hypoglycemia were also investigated in these patients to clarify their contribution to diabetic brittleness. beta-Cell function was evaluated on the basis of elevation of plasma C-peptide immunoreactivity (CPR) during the intravenous glucagon test with a highly sensitive assay for plasma CPR that could detect as little as 0.03 ng/ml. After stimulation with glucagon, a significant increase in plasma CPR was observed in 10 of the patients whose beta-cell function had been evaluated as completely depleted by a conventional assay for plasma CPR. A clear inverse correlation was found between the secretory capacity of pancreatic beta-cells measured in this way and the degree of glycemic instability (r = -.74, P less than .01). Infusion of insulin at a rate of 0.15 U.kg-1.h-1 for 60 min caused a continuous decrease in the plasma glucose level, resulting in neuroglycopenia in 7 of the 10 CPR nonresponders but only 2 of the CPR responders. During insulin-induced hypoglycemia, plasma glucagon immunoreactivity did not increase in the CPR nonresponders but increased significantly in the CPR responders. A positive correlation was found between the minimal residual beta-cell capacity and the responsiveness of alpha-cells to hypoglycemia (r = .65, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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Migration of activated keratocytes toward the corneal stromal wound is one of the most important processes of successful healing. To understand the motility of keratocytes and the interaction of fibronectin and intracellular actin filaments, we cultured rabbit corneal keratocytes and studied dynamic movements of the cells by time-lapse cinematography. We also examined the changes in the localization of fibronectin and actin using double staining immunofluorescent microscopy. The cultured keratocytes first attached to the substratum in round globular shape and then spread with many extending processes. In the early stage of the cultivation, fibronectin was observed inside the cells. Later, fibronectin was observed outside the cells, suggesting formation of the extracellular matrix. When keratocytes spread, actin was observed as a stress fiber inside the cells. At the edge of the cellular processes, a close interaction between fibronectin and actin was observed. The present results demonstrated that cultured keratocytes had active motility and that there were close interactions between the extracellular fibronectin and intracellular actin filaments. The organization of fibrillar actin filaments (F-actin) might be affected by the binding of extracellular fibronectin to the cell surface receptor for fibronectin.
Strategies for the treatment of small cell lung cancer (SCLC) were reviewed depending on the recent results of treatment. The development of new anti-cancer drugs are essential for the further improvement results of SCLC. However, the candidate of patient for phase II study of new anticancer drug is controversial. Intensified chemotherapy is essential in order to obtain long term survivors, however, the toxic death rate should be less than 5% of whole patients. The theory of non-cross resistant alternative chemotherapy has also been applied to the treatment of SCLC. The protocol study supported by grant-in-aid from the Ministry of Health and Welfare is now on-going by cooperative study. There are many discussions about the efficacy of combined modality in SCLC. However, present randomized trials gave clear answers about the priority of combined modality in SCLC. There are numerous biological studies about SCLC. These studies will contribute to improve the treatment results of SCLC.
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Between February 1984 and August 1987, 10 patients with severe aplastic anemia were treated with bone marrow transplantation from HLA-identical sibling donors after preparation with cyclophosphamide (CY) 200 mg/kg and total lymphoid irradiation (TLI) 750 cGy. Ages ranged from 5 to 28 years (median 14 years). All patients were previously transfused. Median number of transfusions was 16 (range, 3-886). For post-transplant immunosuppression all patients were given cyclosporine and the last three patients received additional immunosuppression with short-term methotrexate. All patients had initial engraftment and survived for more than 3-46 months after transplantation. One patient developed significant acute graft-versus-host disease (GVHD) and three of nine recipients who survived more than 100 days developed chronic GVHD. One male patient who had received 21 transfusions from his marrow donor before transplantation suffered from persistent granulocytopenia. Otherwise all have Karnofsky performance scores of 90-100%. Although the number of patients is small, it appears that allogeneic bone marrow transplantation with the regimen of CY + TLI for preparation combined with cyclosporine (+ short-term methotrexate) for post-transplant immunosuppression is a promising modality for treatment of previously transfused patients with severe aplastic anemia.