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Biomedical subjects

M Sugimoto

Publications and source records attributed to M Sugimoto.

At least 343 records · Page 19Linked to original sources

Studies on T-cell colony formation in chronic renal failure (CRF) patients.

In order to study the possibility of abnormal differentiation and proliferation of T-cell precursors in chronic renal failure (CRF), we studied T-cell colony formation in CRF patients. The two-step monolayer method, with phytohemagglutinin-P as the inducer, was used for T-cell colony formation. In our results, colony formation was markedly reduced in CRF patients in comparison with normal controls, with about half of the former showing no colony growth. All cases showed a significant increase in colony numbers with in vitro plasmapheresis (the replacement of autologous plasma in the culture system with normal AB plasma). A significant increase in colony numbers was also seen with the addition of exogenous interleukin-2 (IL-2). The addition of IL-2 in the presence of normal plasma, in particular, induced an increase in colony numbers to near the levels in normal subjects. These results suggest that T-cell precursors exist in near normal numbers in CRF patients and that there are uremic inhibitors in the plasma. A reduced production of IL-2 is also indicated. These factors may be involved in the pathogenesis of immunodeficiency in CRF patients.

Adult↗

[Pathogenesis of pulmonary involvement in HTLV-I-associated myelopathy (HAM): studies on T-cell function].

It has been shown that there are pulmonary involvements in patients with HTLV-1-associated myelopathy (HAM). Pulmonary lesions found in HAM are characterized by T-lymphocytosis and increased levels of soluble IL-2 receptor in bronchoalveolar lavage fluid. Peripheral blood lymphocytes from HAM patients proliferated spontaneously when cultured in vitro. Lymphocytes proliferated were positive for CD3 and HLA-DR staining. There were CD4+ cells and CD8+ cells in proliferating T-lymphocytes 5 days after cultivation. Culture supernatants of proliferating cells showed an increased soluble IL-2 receptor. These results suggest that activated T-cells play an important role in developing pulmonary lesions in HAM.

Adult↗

[A case of pulmonary alveolar proteinosis accompanied with the elevation of CEA (carcinoembryonic antigen) in bronchoalveolar lavage fluid].

A 44-year-old man was admitted with increasing dyspnea and butterfly shadow on his chest roentgenogram. Both the bronchoalveolar lavage and transbronchial lung biopsy (TBLB) led to a diagnosis of pulmonary alveolar proteinosis. CEA level in his bronchoalveolar lavage fluid (BALF) (216.8 ng/ml) was markedly elevated more than that in his serum (50.6 ng/ml). The localization of CEA on TBLB specimen stained by peroxidase-antiperoxidase technique using anti-CEA antibody was investigated and it was found that some alveolar epithelial cells and the material filling the alveoli were positively stained. Functions of alveolar macrophages in BALF were also studied, that is, adherence to glass, cell spreading, the nitroblue tetrazolium reduction, phagocytosis of immunobeads, and the activity of lysosomal enzymes, and found that all of those functions were lower than that of normal smokers. It was suggested that type II alveolar epithelial cells were those which produced and secreted CEA into the alveoli, as they do surfactant-like material in pulmonary alveolar proteinosis, and that the dysfunction of alveolar macrophages was secondary to the overingestion of the proteinaceous material in the alveoli.

Bronchoalveolar Lavage Fluid↗

[In vitro growth of eosinophil colonies from normal human peripheral blood].

Eosinophil colony formation was observed in culture of normal peripheral mononuclear cells in the presence of phytohemagglutinin stimulated peripheral mononuclear cell conditioned medium. The number of eosinophil colonies from 10(6) mononuclear cells varied ranging between 2 and 95, and the mean number was 20.4 +/- 6.3 (SE). A large proportion of total colonies was eosinophil colonies accounted for 81.2 +/- 10.7% of the total colonies.

Cell Division↗

[Significance of isoantigen in the management of the urinary bladder tumor--a basic study of ABO isoantigen in step sections of the entire bladder].

Twenty cases of bladder cancer which had been treated by radical cystectomy were investigated, five out of these twenty were rendered to a specific red cell adherence test (SRCA test) using step section of entire bladder and for the other 15 cases malignant lesions and surrounding non-malignant lesions, which had been determined by histological mapping, were compared using the SRCA test. The SRCA test positive and negative lesions could coexist within the same tumor. Thus in the case of a large tumor, multiple biopsies were required to evaluate the results of the SRCA test. Since multiple bladder cancer lesions of the same patient revealed different results of the SRCA test, each lesion should be evaluated individually. Some dysplasia, down growth and squamous metaplasia were SRCA test negative and this phenomenon was frequently observed in the surrounding tissue of the bladder cancer. Histologically normal bladder epithelium and hyperplasia showed SRCA test positive by 100%. All the CIS showed SRCA test negative. Positive percentage of SRCA test in grade II and grade III tumors were 40% and 23.1% respectively. There was no relationship between the pathological stage and the results of SRCA test. There was no relationship between the existence of the intramural lymphatic invasion and/or the intramural venous invasion and the result of the SRCA test. From these results, we conclude that the SRCA test is a useful tool to predict the malignant potential of the bladder cancer, but when we utilize this test for the bladder biopsy specimens we found its reliability limited.

ABO Blood-Group System↗

[Acute leukemia complicated by hyperbilirubinemia due to high dose cytosine arabinoside therapy].

A 58-year-old man was admitted to our hospital because of low grade fever and purpura in September. 1987. On admission, his bone marrow aspiration showed nucleated cell count of 48 x 10(4)/mm3 with 94.6% of promyelocyte-like leukemic cells. A diagnosis of acute promyelocytic leukemia was made and he was treated with high dose cytosine arabinoside (HDAra C). After this therapy, serum bilirubin, especially direct bilirubin was increased and hyperbilirubinemia was progressed with normal transaminase levels. He had complicated by pneumonia and died of respiratory failure. Autopsy revealed only cholestasis in the liver with neither hepatic cell necrosis nor cell infiltration. This case was though to be a rare case with cholestatic liver injury due to HDAra C.

Cholestasis, Intrahepatic↗

[Eosinophilic lymphofolliculosis (Kimura's disease) complicated with aortitis syndrome].

A 47 year-old-man was admitted because of mild congestive heart failure. A differential white blood cell count revealed eosinophilia and a biopsied inguinal lymph node showed well-developed lymphoid follicles with germinal centers, eosinophil infiltration and marked proliferating vessels with swollen endothelial cells. He was diagnosed as eosinophilic lymphfolliculosis (Kimura's disease). He also was hypertensive and vascular murmur was pointed out in his abdomen. Angiography revealed the complication of aortitis syndrome. Renal complication in eosinophilic lymphfolliculosis was reported in some cases and it was though that the disease had a clinical aspect of systemic diseases. The complication of aortitis syndrome in our case is interesting from a point of view of eosinophilic lymphfolliculosis as a systemic disease.

Angiolymphoid Hyperplasia with Eosinophilia↗

[Factor V inhibitor with double cancer].

A 84-year-old man was admitted with palpitation, edema of legs and anemia during a long course of diabetes mellitus, prostatic hypertrophy and prostatic cancer. He revealed purpura on the hands and massive microhematuria. He had received antibiotic therapy for a urinary tract infection for a period of time, but he had no history of hemorrhagic tendency or blood transfusion. Coagulation studies showed the prolongation of whole blood clotting time and PT (prothrombin time). Activity of factor V was 14% of that normal control plasma. The titer of factor V inhibitor was 4.9 Bethesda units/ml. The inhibitor of the patient was supposed to belong to IgA and IgG judging from inhibitor neutralization test. PT was improved after discontinuance of administration of antibiotics and administration of azathioprine. Moreover, even after administration of prednisolone with antibiotics, PT and activity of factor V recovered to normal range. He died from respiratory failure. Autopsy revealed double cancer of prostate and descending colon. The appearance of factor V inhibitor was likely caused by antibiotics, double cancer, and age-related immune disorders.

Aged↗

T-cell colony formation in homosexual men with anti-human immunodeficiency virus.

In vitro differentiation and proliferation of precursor T-cells was examined in four homosexual men positive for anti-human immunodeficiency virus (HIV), one of whom had acquired immunodeficiency syndrome (AIDS). Peripheral mononuclear cells from the men were cultured with phytohemagglutinin-P in semi-solid culture media containing methylcellulose for 7 days. Colony formation was significantly reduced in all subjects, even in the presence of IL-2. Moreover, numerous colony component cells lacked T-cell specific surface markers. These results suggest that the impaired T-cell differentiation and proliferation occurs at the precursor T-cell level in HIV infection.

Acquired Immunodeficiency Syndrome↗

[Antibiotics-induced agranulocytosis. Patient's IgG inhibits a GM colony formation].

The pathogenesis of Cefmetazole (CMZ) induced agranulocytosis was investigated in the case of a 40-year-old man who developed agranulocytosis while he was under treatment with CMZ. Although concentration of CMZ in serum is not detected, patient's serum drawn at the time of diagnosis suppressed normal allogeneic marrow GM colonies in vitro. Normal IgG purified from serum had no effect on GM colony formation in vitro. However, patient's IgG purified from serum drawn at the time of diagnosis suppressed normal allogeneic marrow GM colony in vitro without CMZ. These studies suggest that CMZ-induced agranulocytosis is immunologically mediated through an IgG inhibitor which seems to exert its effect on GM colony formation.

Adult↗

[T-lymphocytosis and increased levels of soluble IL-2 receptors in bronchoalveolar lavage fluid in cases of HTLV-I-associated myelopathy with pulmonary involvement].

HTLV-I-associated myelopathy (HAM) is endemic in southwest Japan and frequently shows T-lymphocyte alveolitis. In the present study, we investigated 13 patients with HAM to determine if they showed increased levels of soluble IL-2 receptors, a marker of lymphocyte activation, in bronchoalveolar lavage (BAL) fluid. BAL studies showed that there was an increased proportion of lymphocytes in BAL fluid from HAM patients. The increased BAL lymphocytes consisted mainly of CD3+ cells and CD4+/CD8+ ratios were similar to those of normal controls. Serum levels of soluble IL-2 receptors were significantly elevated in patients with HAM as compared to normal controls (685 +/- 210 vs 286 +/- 49 U/ml, p less than 0.01). BAL levels of soluble IL-2 receptors were detectable in patients with HAM and these levels were approximately 13 times higher on average than those in serum (166 +/- 103 vs 18 +/- 13 U/mg albumin, p = 0.001). BAL Il-2R levels in patients with HAM correlated well with the number of T-lymphocytes and CD4+ cells in BAL fluid. These results suggest that T-lymphocytes infiltrating the lungs of HAM patients are activated locally to produce IL-2 receptors. In conclusion, immunological mechanisms seem to be responsible for the development of pulmonary lesions in patients with HAM.

Adult↗

[Sex difference in alcoholic liver disease: with special reference to the severity of alcoholic hepatitis].

Purpose of this study was to elucidate the difference in severity of alcoholic liver diseases (ALD), especially of alcoholic hepatitis (AH) between female and male. We have experienced 15 female and 113 male patients with ALD laparoscopically and histologically proved during the past 10 years. In female patients, histological analysis revealed 8 cases of cirrhosis, 2 each cases of AH, fibrosis and chronic hepatitis, and 1 case of fatty liver. Occurrence of AH in female (13%) was significantly higher than male in which AH was seen in 3 cases (3%) (p less than 0.05). Duration of alcoholic abuse in female AH patients was shorter than male AH patients (5.5 +/- 0.5 years vs 24.0 +/- 2.9 years). Total alcohol consumed in female AH patients was less than male AH patients (256 +/- 52 kg vs 1560 +/- 703 kg). Abnormality in liver function tests including hepaplastin test, serum bilirubin, transaminases, lactate dehydrogenase, alkaline phosphatase, gamma-glutamyltranspeptidase, immunoglobulins was outstanding in female patients compared with male patients. Histological findings such as hepatocellular ballooning, neutrophilic infiltration, fatty change and wiremesh fibrosis were intensive in female patients compared with male patients. In conclusion, there were much more severe ALD like AH or cirrhosis in female than male patients. In female AH patients duration of alcoholic abuse was shorter and total alcohol consumed was less than male AH patients. And it was suggested that female AH is clinically and pathologically getting severe compared with male AH.

Adult↗

Chromosomal reorganization for the expression of recessive mutation of retinoblastoma susceptibility gene in the development of osteosarcoma.

Recent evidence indicates that the mutation of retinoblastoma susceptibility (RB) gene is also involved in the development of osteosarcoma. We studied 30 cases of osteosarcoma for the structural anomalies of the RB gene by Southern hybridization analysis with cDNA probes of the RB gene. Thirteen cases (43%) showed structural anomalies of the RB gene. They included the total or partial deletion, or rearrangement of the RB gene; seven with homozygous deletions and six with hemizygous deletions or rearrangements. By the use of restriction fragment length polymorphism fragments as chromosome markers, those seven tumors having homozygous deletions and four of six tumors having hemizygous anomalies showed the loss of heterozygosity at other loci on chromosome 13. Among those tumors with no apparent structural changes of the RB gene, seven cases showed the loss of heterozygosity on chromosome 13, and altogether the loss of heterozygosity by either homozygosity or hemizygosity was found in 18 (64%) of 28 informative cases. The loss of heterozygosity was also found for nine of 10 other chromosomes, of which chromosome 17 showed the highest frequency (77%). The tumors with loss of chromosome 13 alleles also showed additional losses of alleles on other chromosomes, while tumors retaining heterozygosity of chromosome 13 also retained heterozygosity at the informative loci on other chromosomes. Southern hybridization and karyotype analysis in some selected cases suggest that the concerted loss of heterozygosity at multiple loci may be a consequence of the polyploidization-segregation process.

Adolescent↗

A total synthesis of hematoside, alpha-NeuGc-(2----3)-beta-Gal-(1----4)-beta-Glc-(1----1)-Cer.

Methyl (5-acetoxyacetamido-4,7,8,9-tetra-O-acetyl-3,5- dideoxy-D-glycero-beta-D-galacto-2-nonulopyranosyl chloride)onate, prepared from N-glycolyl-neuraminic acid, was used for the glycosylation of benzyl O-(2,6-di-O-benzyl-beta-D- galactopyranosyl)-(1----4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside to give benzyl O-[methyl (5-acetoxyacetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero- alpha- and beta-D-galacto-2-nonulopyranosyl)onate]-(2----3)-O-(2,6-di-O -benzyl-beta- D-galacto-pyranosyl)-(1----4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside, and a regioisomer. Compounds 9 and 13 were converted into the corresponding glycotriaosyl glycosyl donors which, upon coupling with (2S,3R,4E)-3-O-tert-butyldiphenylsilyl-2-N- tetracosanoylsphingenine, afforded completely protected hematoside and a stereoisomer 26, respectively. Deprotection of 22 and 26 completed the first total synthesis of both hematoside and a stereoisomer, beta-NeuGc-(2----3)-beta-Gal-(1----4)-beta-Glc-(1----1)-Cer.

Carbohydrate Conformation↗

Comparison of epi-GM3 with GM3 and GM1 as stimulators of neurite outgrowth.

A variety of naturally occurring ganglioside structures were previously shown to be effective agents for inducing neurite outgrowth of primary neurons and neuroblastoma lines. We report here the results of similar experiments with a synthetic epimer of GM3 (epi-GM3) possessing a neuraminidase-resistant beta-ketosidic linkage. This substance was found to enhance neuritogenesis toward two transformed cell lines (neuro-2A, PC-12) and one primary neuronal tissue (dorsal root ganglia). The results indicate that the stereochemistry of the ketoside linkage is not critical and that metabolism of exogenous ganglioside by the treated cells is not involved directly in the neuritogenic phenomenon.

Animals↗

Construction of promoter-probe vectors for Candida maltosa, a n-alkane-assimilating yeast, using the LEU2 gene of Saccharomyces cerevisiae.

For the purpose of isolation of promoter regions which are regulated by a carbon source in the medium in an n-alkane-assimilating yeast, Candida maltosa, two promoter-probe vectors were constructed. Each of them consists of the LEU2 gene of Saccharomyces cerevisiae whose 5'-noncoding region was trimmed with BAL31, an autonomously replicating sequence isolated from C. maltosa genome (the TRA region) which we have previously isolated, and the pBR322 sequence. One of them, pPLC2, having the TATA box, lacks the regulatory sequence ("sequence L") of the LEU2 gene, and the other, pPLC1, lacks both the TATA box and sequence L. Using pPLC1 as a short-gun cloning vector in C. maltosa, many promoter regions which were active when glucose was present in the medium as a carbon source were obtained from the genome of C. maltosa. The sizes of the inserted fragments of two of them were determined. (In this paper, a promoter region refers to a promoter which includes a TATA box, plus a regulatory sequence such as an UAS (upstream activating sequence)-like sequence).

Candida↗

Immunogenicity of a recombinant vaccinia virus expressing envelope a glycoprotein of bovine leukaemia virus.

We constructed a recombinant vaccinia virus (RVV) expressing envelope (env) glycoprotein (gp51) of bovine leukaemia virus (BLV): the expression of gp51 was detected by Western blot of the lysates of rabbit kidney cells infected with the RVV. The rabbits inoculated intradermally with the RVV alone failed to induce detectable anti-gp51 antibodies even 10 weeks after immunization. However, when these animals were boosted with inactivated BLV virion in saline, significant levels of anti-gp51 antibodies were induced as shown both in Western blot and immunodiffusion analyses. In these animals, antibodies against gag product (p24) were not detected. On the other hand, the rabbits inoculated with wild-type vaccinia virus and boosted similarly three times with the BLV virion in saline did not induce detectable anti-gp51 antibodies at all. The present experiment revealed that the RVV possessed the capability to endow immunological memory without inducing apparent anti-gp51 antibody responses, meaning that the RVV activated helper T cells far more strongly than B cells. The applicability of the RVV to vaccine development is discussed.

Animals↗

Blood clotting factor IX Niigata: substitution of alanine-390 by valine in the catalytic domain.

Factor IX Niigata is a mutant factor IX responsible for the moderately severe hemophilia B in a patient who has a normal level of factor IX antigen with reduced clotting activity (1-4% of normal). We reported previously that the purified mutant protein could be converted to the factor IXa beta form by factor XIa/Ca2+ at a rate similar to that in the case of normal factor IX, but the resulting mutant factor IXa beta could not activate factor X in the presence of factor VIII, Ca2+, and phospholipids (Yoshioka, A. et al. (1986) Thromb. Res. 42, 595-604). In the present study, we analyzed factor IX Niigata at the structural level to elucidate the molecular abnormality responsible for the loss of clotting activity. Amino acid sequence analysis of a peptide obtained on lysyl endopeptidase digestion, coupled with subsequent SP-V8 digestion, demonstrated that the alanine at position 390 was substituted by valine in the catalytic domain of the factor IX Niigata molecule.

Alanine↗