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Biomedical subjects

M Sugimoto

Publications and source records attributed to M Sugimoto.

At least 307 records · Page 17Linked to original sources

[A case of HTLV-1 associated myelopathy progressed in course over 30 years].

A 66-year-old female suffering from HTLV-1 associated myelopathy (HAM) for more than 30 years was hospitalized because of memorial impairment, deafness, dysarthria, dysphagia, and complete paraplegia. She first noticed stiffness and weakness of the right leg at 35 years of age. Gait disturbance was slowly progressed and complete paraplegia developed 18 years later. Neurological examinations on admission revealed that she was bedridden with decubitus, mental deterioration (pre-dementia of subcortical type), bilateral optic nerve atrophy, severe sensory-neural deafness, dysarthria, complete paraplegia, and marked neurogenic bladder. Laboratory data showed mild normocytic anemia and moderate diabetes mellitus. Anti-HTLV-1 antibody titers in serum and CSF were 78,192X and 1,024X, respectively (PA method). Serum levels of soluble IL-2 receptor was markedly elevated (2,200 U/ml). Peripheral blood lymphocytes showed spontaneous proliferation when cultured for 5 days (3H-thymidine uptake; 45,285 cpm/5 X 10(4) cells). MRI examinations of the spinal cord disclosed a predominant atrophy of lower thoracic cord without any compressive lesions. Brain MRI showed diffuse high intensity lesions of the periventricular area on T2 weighted images. Such abnormalities were predominantly found in fronto-parietal region and were quite similar to those of leuko-ariosis. Single photon emission CT using 123I-iodoamphetamine showed hypoperfusion of cerebral white matter on delayed image. It has been reported that intellectual impairment and brain atrophy are not usually seen in HAM patients. The present case, however, shows that such abnormalities of the central nervous system could occur in HAM patients with a long duration of illness.

Aged↗

[Bronchoalveolar lavage studies in a HTLV-1-positive case associated with interstitial pneumonia].

A 64-year-old housewife was hospitalized because of cough and dyspnea. Chest X-rays on admission showed diffuse interstitial shadows and loss of lung volume, suggesting acute interstitial pneumonia. Pulmonary function tests revealed decreased vital capacity and severe hypoxemia. Bronchoalveolar lavage studies showed that total cell counts and a proportion of lymphocytes were increased. Lymphocytes increased in lavage fluid consisted mainly of T cells with an elevated CD4+/CD8+ ratio. Furthermore, these lymphocytes spontaneously proliferated and responded well to recombinant IL-2 when cultured in vitro for 5 days, suggesting that lymphocyte activation occurred in the lung. Such lavage findings and lymphocytes activation in association with the presence of HTLV-1-specific IgA antibody in lavage fluid have been demonstrated in patients with HTLV-1-associated myelopathy. In this patient positive for HTLV-1, however, it could not be determined whether the pulmonary lesions were primarily related to HTLV-1 infection, because no IgA antibody specific for HTLV-1 was demonstrated in lavage fluid. In conclusion, when pulmonary abnormalities are found in HTLV-1 carriers, we should be careful in determining whether such pulmonary involvements are etiologically related to HTLV-1 infection.

Bronchoalveolar Lavage Fluid↗

[Gabexate mesilate induced remarkable transient reversal of thrombocytopenia in a ITP patient].

A 46-year-old woman was admitted to our hospital because of hemorrhagic tendency. Normal coagulation test results conflicted with the diagnosis of disseminated intravascular coagulation (DIC). Furthermore, we saw no evidence of autoantibodies, including antinuclear antibodies and splenomegaly, and there was no past history of infection or medication. Peripheral blood test showed marked decrease of platelets only. Bone marrow aspiration revealed increased megakaryocytes. Morphology of other blood components was normal. Thus, we diagnosed this case as idiopathic thrombocytopenic purpura (ITP). Administration of prednisolone and an immunosuppressants did not improve symptoms. So patient was temporarily discharged and treated with 6-MP at the outpatient department. She was rehospitalized for liver damage caused by the drug. Patient then developed sepsis from acinetobactor. We administered gabexate mesilate (FOY, 2,000 mg/day) for four days to prevent DIC. Platelet count, which was 1.5 X 10(4)/microliter before FOT administration, began increasing on the second day, reaching 25. 5 X 10(4)/microliter on the fourth. Count rapidly decreased to 2.8 X 10(4)/microliter on the seventh day after administration had been discontinued. Two-time FOY administration after patient's recovery from sepsis led to a definite, similar transient increase in platelet count. As ITP patients with transient increase in platelet count by FOY administration had not been reported, this case is thought to be an interesting case in the pathogenesis and treatment of ITP.

Female↗

An efficient synthesis of ganglioside GM3: highly stereocontrolled glycosylations by use of auxiliaries.

An efficiently stereocontrolled total synthesis of GM3 alpha-D-Neup5Ac-(2----3)-beta-D-Galp-(1----4)-beta-D-Glcp-(1----1) -Cer was achieved by employing both methyl 5-acetamido-4,7,8,9-tetra-O-benzyl-2-bromo-2,3,5-trideoxy-3- phenylthio-D-erythro-beta-L-gluco-2-nonulopyranosonate for the key sialylation step, and O-[methyl(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha -D-galacto-2-nonulopyranosyl)onate]-(2----3)-O-(2,4,6-tri-O- acetyl-beta-D-galactopyranosyl-(1----4)-3,6-di-O-acetyl-2-O-pivaloyl- alpha-D-glucopyranosyl trichloroacetimidate and fluoride for the key coupling step with a ceramide derivative. These two steps were significantly altered and improved in comparison with our previous synthesis that had been executed without use of stereocontrolling auxiliaries. GM3 was obtained in 4.5% overall yield in 19 steps starting from allyl O-(2,6-di-O-acetyl-3,4-O-isopropylidene-beta-D-galactopyranosyl)-(1----4 )-2,3,6-tri-O-acetyl-beta-D-glucopyranoside.

Carbohydrate Conformation↗

Benzeneselenenyl triflate as an activator of thioglycosides for glycosylation reactions.

A new method for the activation of thioglycosides was developed by use of benzeneselenenyl triflate (PhSeOTf), which, upon reaction with either a primary or secondary sugar HO-group, afforded O-glycosides under extremely mild reaction conditions. The reaction was applicable to various l-thiohexosides 2-6 as well as to a 2-thioglycoside 20 derived from N-acetylneuraminic acid (NeuAc).

Carbohydrate Sequence↗

A monoclonal antibody to free N-acetylneuraminic acid.

A monoclonal antibody (70-A) to free N-acetylneuraminic acid was obtained by immunizing mice with its synthetic beta-glycoside, sodium O-[(5-acetamido-3,5-dideoxy-D-glycero-beta-D-galacto-2- nonulopyranosyl)onate]-(2----3)-1,2-di-O-tetradecyl-sn-glyce rol, followed by fusing the isolated spleen cells with mouse myeloma cells and cloning positive fusions. 70-A reacted with various synthetic beta-glycosides of N-acetylneuraminic acid and also with cytidine-5'-monophosphate-N- acetylneuraminic acid, known as its sole naturally occurring beta-glycoside. The inhibition assay showed that N-glycolylneuraminic acid had slightly lower reactivity than N-acetylneuraminic acid, but other monosaccharides tested, such as N-acetylglucosamine, N-acetylgalactosamine or N-acetylmannosamine, had no reactivity toward 70-A. Reactivity of 70-A with free N-acetylneuraminic acid was confirmed by measuring the specific binding of N-[14C]acetylneuraminic acid to the antibody. The association constant of 70-A with N-acetylneuraminic acid was determined to be 5.96.10(4) M-1 by equilibrium dialysis.

Animals↗

Elevated frequency of a specific allele of the L-myc gene in male patients with bone and soft-tissue sarcomas.

Restriction fragment length polymorphisms (RFLPs) of 2 oncogenes, c-Ha-ras and L-myc, have been analyzed in 101 patients with bone and soft-tissue sarcoma and in 98 normal individuals. The c-Ha-ras gene was highly polymorphic both in sarcoma patients and in normal individuals. In contrast to our previous observation in breast cancer patients (Honda et al., 1988), no significant difference in allele frequencies between normal and sarcoma populations was observed. The L-myc locus revealed 2-allele polymorphism, allele L (10-kb) and S (6.6-kb), after digestion with Eco RI. The allele frequencies of L and S in sarcoma patients were 0.381 and 0.619, respectively, and those in normal individuals were 0.485 and 0.515, respectively. While the distributions of alleles in both populations fitted well with the Hardy-Weinberg equilibrium, the frequency of the S allele was significantly higher in sarcoma patients than in normal individuals (p less than 0.05). When sarcoma patients were divided into male and female subpopulations, this difference was highly significant only in males (p less than 0.01) but not in females. Our results suggest that males carrying the S allele may be prone to develop sarcoma.

Alleles↗

[Pulmonary involvement in HTLV-I-associated myelopathy].

Patients with HTLV-I-associated myelopathy (HAM) show subclinical pulmonary involvement. Bronchoalveolar lavage (BAL) studies of HAM patients have shown that there is T-lymphocytosis in association with increased soluble IL-2 receptor levels in BAL fluid. Furthermore, BAL lymphocytes as well as peripheral blood lymphocytes obtained from HAM patients proliferated spontaneously when cultured in vitro. The lymphocytes proliferating were T-lymphocytes (both CD4+ cells and CD8+ cells) and released soluble IL-2 receptors in supernatant fluid. These results indicated that T-lymphocytes were activated in HAM patients. In conclusion, activated T-lymphocytes may play an important role in the development of the spinal cord and pulmonary lesions in HAM patients.

Adult↗

Reovirus transport--studies using lymphocytosis promoting factor.

To explore how bacteria and their products may modulate viral infection, we investigated the effect of a well-characterized and highly purified product of Bordetella pertussis, a pertussis toxin, also known as lymphocytosis promoting factor (LPF), on enteric reovirus infection. LPF is known to have a variety of effects, including modulation of circulation and homing of lymphoid cells. When adult mice are inoculated with reovirus type 1 perorally, reovirus first enters the Peyer's patches (PP) through M cells, and then spreads to mesenteric lymph nodes (MLN) and spleen with minimal dissemination to other peripheral tissues. In view of the profound effect of LPF on lymphoid tissues, we evaluated whether LPF might influence the early stages of type-1 reovirus infection following peroral inoculation. Pretreatment of adult BALB/c mice with LPF significantly inhibited the spread of reovirus in a manner dependent upon the route of inoculation; LPF inhibited the extra-intestinal spread of virus from PP to MLN after intragastric inoculation; in contrast there was enhancement of the spread of blood-borne viruses to MLN after intravenous inoculation. This result, together with the fact that the efferent lymph from PP reaches MLN, suggests that a proportion of reoviruses were conveyed from PP to MLN in association with lymphoid cells along the lymphatic channels and that LPF affects reovirus, in part, by blocking cell movement.

Animals↗

Silent thyroiditis following rubella.

A 40-year-old housewife was referred to our hospital for evaluation of a thyrotoxic state. A month after rubella infection, she developed heat intolerance. Physical examination revealed a hard and non-tender goiter with no signs or symptoms of inflammation. Free thyroid hormones were high and TSH was undetectable. 123I-thyroidal uptake was suppressed. Antithyroglobulin and anti-microsomal antibodies were negative throughout the course. A serologic study revealed high levels of anti-rubella antibodies. After a month without any treatment, she became euthyroid. Free thyroid hormones and TSH gradually became normal and the antibodies to rubella decreased. 123I-thyroidal uptake increased. From the clinical course, the patient was diagnosed as having silent thyroiditis. We suggest that viral infection such as rubella could cause the development of silent thyroiditis.

Adult↗

The classification of the low birth-weight infants from the viewpoint of mental development.

Periodical checkups on 206 infants were carried out in order to elucidate which of various factors would pose decisive influence upon the retardation of mental development after birth with the AIKEN method. Correlations between average DQ (development quotient) and figures of physical measurements at birth were sought after. Consequently, weeks of gestation, body weight, cephalic circumference and body length at birth revealed certain correlation with the retardation of mental development. Multiple regression analysis disclosed highly significant correlations of body length and cephalic circumference toward the birth weight. Therefore, both weeks of gestation and birth weight are the direct contributory factors to average development quotient. Based on this result, a prediction equation for the mental development after birth has been proposed. Low average DQ was found in high percentages among infants born with toxemia of pregnancy or premature rupture of membranes. However, it is suggested that they are not the direct causes of such retardation, but are rather provoking short weeks of gestation and low birth weight. In summary, the newborn with less than 37 weeks of gestation and below 2,000 grams of birth weight would be named and classified as a SFD (small for dates) with the problem for mental development (MD-SFD).

Birth Weight↗

Spontaneous T cell proliferation and release of soluble interleukin-2 receptors in patients with HTLV-I-associated myelopathy.

Patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) show increased serum levels of soluble interleukin-2 receptors (sIL-2R), a marker of T cell activation. We found that peripheral blood lymphocytes from HAM patients proliferated spontaneously and released sIL-2R when cultured in vitro. Spontaneous proliferation was observed in T cell populations (both CD4+ cells and CD8+ cells), but not in B cell-rich populations or monocyte-rich populations. There was a significant increase of IL-2 activity in the culture supernatants of peripheral blood mononuclear cells (PBMC) after 2-3 days cultivation. On the other hand, sIL-2R concentrations in the supernatants were much higher after 5 days of cultivation. Such spontaneous T lymphocytic proliferation and release of sIL-2R were also found in non-HAM HTLV-I carriers, but not as intensely as in HAM patients. HTLV-I infection causes T cell activation to release IL-2 and sIL-2R; such T cell responses may play a role in the pathogenesis of HTLV-I-associated myelopathy.

Adult↗

[Clinical significances of intraoperative radiation therapy for aged patients with bladder cancer].

Seven elderly patients, 79-88 years old, with bladder cancer were treated by transvesical tumorectomy with intraoperative radiation therapy (IORT). The cancers appeared to be of high grade and high stage by cystoscopy and other examinations, and consequently they were diagnosed to be over stage T2. Therefore, all patients were thought to be candidates for total cystectomy. But their ages and complications precluded this treatment, so we decided to carry out the "palliative" IORT. The operation of IORT required less than two hours and required less than 200 ml of blood loss. There were no complications such as hematuria, irritable bladder, and rectal symptoms. The postoperative stage diagnoses coincided with the preoperative ones in 5 cases, but two cases were overdiagnosed. Five patients died after more than one year and 11 months, but four patients died due to other diseases, without cancer. One patient died due to pulmonary cancer confirmed by autopsy. Recurrence was seen in one case. These results confirmed that IORT was effective for local control of bladder cancer and partially prophylactic for recurrence. Furthermore, this treatment seemed to be even curative for some cases. We recommend this modality of treatment for some of aged patients and patients with complications who are unable to undergo cystectomy.

Aged↗

[A clinical study of 124 cases of renal cell carcinoma].

One hundred twenty-four cases of renal cell carcinoma treated at Department of Urology, The University of Tokyo were analyzed for their clinical characteristics and prognosis. To be noted were the recent increase of incidentally detected cases, kidney-sparing technique in curative surgery and adjuvant therapy using biological response modifiers. Prognosis was more favorable in cases with incidental detection, normal ESR or cystic pattern in pathological architecture, whereas that of cases with metastatic lesions or Grade 3 tumors was ominous. Tumor stage as TUMV or Robson stage was useful to predict the prognosis, although one stage contained cases of considerably different survival periods. These results suggested that the efforts to improve prognosis in the present practice should include early detection of renal cancer by promoting health check-up and development of preventive measure of postoperative recurrence. A more proper staging system might also be needed to analyze clinical studies.

Carcinoma, Renal Cell↗

[Idiopathic thrombocytopenic purpura complicated with circulating lupus anticoagulant].

A 37 year-old female was admitted to our hospital because of hypermenorrhea, prolonged bleeding time, thrombocytopenia and the diagnosis of idiopathic thrombocytopenic purpura (ITP) was made. Though activated partial thromboplastin time (APTT) was markedly prolonged, her coagulation factors were within normal ranges. Activities of the circulating lupus anticoagulant (LAC) was suggested. Kaolin clotting time of the platelet poor plasma was used as a sensitive screening test using the mixture of normal and patient's plasma for the detect of LAC. As a result, LAC positive pattern was observed. The treatment with high-dose gammaglobulin brought out a transient increase of the platelet count, but the prolongation of APTT was not corrected. Both the platelet count and the prolongation of APTT were significantly improved after the treatment with betamethasone.

Adult↗

Induction of neutralizing antibodies against bovine leukosis virus in rabbits by vaccination with recombinant vaccinia virus expressing bovine leukosis virus envelope glycoprotein.

Three kinds of recombinant vaccinia virus (RVV)--mO-HA/ATI, LO1-HA/ATI and mO-HA/7.5kD--expressing bovine leukosis virus (BLV) envelope glycoprotein (gp60) were constructed. The BLV envelope gene of RVV mO-HA/ATI and LO1-HA/ATI or of RVV mO-HA/7.5kD was expressed under control of the promoter of A-type inclusion body (ATI) protein gene of cow-pox virus or vaccinia virus 7.5-kD protein gene, respectively. The vaccinia virus strain, LC16mO, was used as vector for RVV mO-HA/ATI and mO-HA/7.5kD, and strain LO-1 was used for RVV LO1-HA/ATI. Strains LC16mO and LO-1 are attenuated vaccine virus strains originating from the Lister original vaccinia virus. All 3 kinds of constructed RVV expressed gp60 in cultured rabbit kidney cells after infection; mO-HA/ATI expressed more antigen than did mO-HA/7.5kD. Rabbits vaccinated with RVV produced considerable antibody capable of inhibiting syncytium formation, as well as antibody with virion-binding ability. The RVV that used ATI promoter induced higher antibody titer than did the RVV that used 7.5-kD promoter. Results indicate that BLV gp60 is responsible for induction of neutralizing antibodies that suppress in vitro formation of syncytia among BLV-infected cells. Applicability of RVV, especially those using ATI promoter, was evaluated in a vaccine against bovine leukosis.

Animals↗