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Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

At least 667 records · Page 37Linked to original sources

Diversity of HLA-B17 alleles and haplotypes in East Asians and a novel Cw6 allele (Cw*0604) associated with B*5701.

The distribution of HLA-B17 alleles and their association with HLA-A, -C and -DRB1 alleles were investigated in seven East Asian populations Japanese, South Korean, Chinese-Korean, Man, Northern Han, Mongolian and Buryat populations). The B17 alleles were identified from genomic DNA using group-specific polymerase chain reaction (PCR) followed by hybridization with sequence-specific oligonucleotide probes (SSOP). In all of these East Asian populations, except Japanese and Chinese-Koreans, B*5701 was detected and strongly associated with A*0101, Cw*0602 and DRB1*0701. In contrast, B*5801 was detected in all the seven populations and strongly associated with A*3303, Cw*0302, DRB1*0301 and DRB1*1302. The A*3303-Cw*0302-B*5801-DRB1*1302 haplotype was observed in South Korean, Chinese-Korean, Buryat and Japanese populations, while A*3303-Cw*0302-B*5801-DRB1*0301 was predominantly observed in the Mongolian population. A similar haplotype, A*0101-Cw*0302-B*5801-DRB1*1302, was observed in the Buryat population. A novel Cw6 allele, Cw*0604, was identified in the Man population. This Cw allele was observed on the haplotype A*0101-B*5701-DRB1*0701. Thus, we confirmed, at the sequence level, that the common haplotypes carrying B*5701 and B*5801 have been conserved and shared in East Asian populations.

Alleles↗

Molecular remission in adult T cell leukemia after autologous CD34+ peripheral blood stem cell transplantation.

This report describes a patient with acute-type adult T cell leukemia/lymphoma (ATLL) successfully treated by autologous CD34+ peripheral blood stem cell transplantation after fractionated total body irradiation and high-dose cytarabine and cyclophosphamide. A newly established inverse polymerase chain reaction method was used to demonstrate the disappearance of ATLL clonal cells. The patient achieved a sustained molecular remission after transplantation, but died from opportunistic infection 4 months after transplantation. Thus, autologous CD34+ peripheral blood stem cell transplantation is promising for this type of malignancy. However, a prudent clinical attitude toward immunological fragility after transplantation is needed for better outcome.

Antigens, CD34↗

Sodium butyrate blocks interferon-gamma (IFN-gamma)-induced biosynthesis of MHC class III gene products (complement C4 and factor B) in human fetal intestinal epithelial cells.

Human intestinal epithelial cells have been established as local sites for complement biosynthesis. In this study, we investigated the effects of IFN-gamma and sodium butyrate on biosynthesis of MHC class III gene products (complement C4 and factor B) in the human fetal intestinal epithelial cell line INT-407. IFN-gamma induced a dose- and time-dependent increase in C4 and factor B secretion. However, sodium butyrate dose-dependently inhibited IFN-gamma-induced C4 and factor B secretion. These effects were also observed at the mRNA level. Immunoblotting indicated that IFN-gamma induced a rapid activation of Stat1alpha, and fluorescence immunohistochemistry detected a translocation of Stat1alpha into the nucleus within 1 h. However, the translocation of Stat1alpha was not affected by the addition of sodium butyrate. Nuclear run-on assay indicated that IFN-gamma induced a weak increase in the transcription rate of factor B gene, and sodium butyrate did not affect this response. IFN-gamma and sodium butyrate induced a counter-regulatory effect on C4 and factor B secretion: IFN-gamma acted as a potent inducer, but sodium butyrate potently abrogated these responses. These are mainly regulated through the post-transcriptional mechanism.

Blotting, Northern↗

Bone turnover and cortical bone mineral density in the distal radius in patients with hyperthyroidism being treated with antithyroid drugs for various periods of time.

OBJECTIVE: Whether patients, who have lost bone mass, can be restored to age-matched control levels by some means is still controversial. We investigated how the thyroid status after antithyroid drug therapy for various periods of time affects bone metabolism in patients with hyperthyroidism by assessing currently used biochemical markers of bone turnover and distal radius bone mineral density (BMD). DESIGN AND PATIENTS: The biochemical markers of bone turnover and BMD at the distal one third of the radius were measured in 79 women with hyperthyroidism treated with antithyroid drugs for various periods of time. The patients were divided into two groups according to thyroid function at the time of study: a hyperthyroid group (serum thyroid stimulating hormone (TSH) < 0.4 mU/l) and an euthyroid group (TSH 0.4-4.0 mU/l). Second, each group was further divided according to the duration of therapy: short-term (less than 3 years) and long-term (3 or more years). MEASUREMENTS: Urinary type I collagen degradation products (CTx) were measured by the CrossLapsTM ELISA kit. Urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured by high performance liquid chromatography (HPLC) after acid hydrolysis. Serum N-mid osteocalcin (OCN-mid) was measured by a recently developed enzyme-linked immunosorbent assay. Serum alkaline phosphatase (ALP) was determined by routine laboratory methods. Bone mineral density (BMD) at the distal one third of the radius was measured using dual energy X-ray absorptiometry (DEXA; DCS-600EX, Aloka, Tokyo). RESULTS: There were statistically significant positive correlations of FT3 and FT4 with the biochemical markers of bone turnover. There were significant negative correlations between the biochemical markers and BMD only in patients undergoing long-term therapy. In a comparison between hyperthyroid and euthyroid groups based on duration of treatment (long-term and short-term), and in a comparison without regard for length of treatment (all patients), it was evident that ALP and CTx levels were significantly higher in the hyperthyroid than in the euthyroid groups. Significantly lower BMD Z-scores in the hyperthyroid group compared to those in the euthyroid group were observed only in patients undergoing long-term therapy. CONCLUSIONS: Urinary type I collagen degradation products were a sensitive marker for evaluating the bone turnover in patients with hyperthyroidism. Our data suggested that it might be important to control the levels of TSH within normal ranges during long-term antithyroid drug therapy in order to prevent bone loss.

Adult↗

Aeromonas sobria infection with severe soft tissue damage and segmental necrotizing gastroenteritis in a patient with alcoholic liver cirrhosis.

A 49-year-old man, who had a 3-year history of liver dysfunction but had not been treated, was admitted to the hospital with a sudden onset of fever and generalized muscle pain. He subsequently developed generalized purpura with scattered hemorrhagic bullae of the skin and massive bloody stools. Aeromonas sobria was proven by culture of both blood and bullous fluid. In spite of the extensive treatment with antibiotics and other medications in the intensive care unit (ICU), the patient went into septic shock and died 2 days after admission. Pathological examination on autopsy revealed segmental necrotizing gastroenteritis with bacterial colonies and alcoholic liver cirrhosis, in addition to extensive severe soft tissue damage involving cellulitis and rhabdomyolysis and epidermolysis. Although the prognosis for Vibrio vulnificus infection with severe soft tissue damage in patients with liver cirrhosis, malignancy, diabetes mellitus or other pre-existing diseases is poor, the unfavorable progression of Aeromonas species, especially A. sobria infection is rare. This is thought to be the first report of an autopsied case.

Aeromonas↗

Effects of lipid-lowering drugs on intermediate-density lipoprotein in uremic patients.

BACKGROUND: Patients with chronic renal failure often have alterations in lipoprotein profile including elevated very-low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL), and reduced high density lipoprotein (HDL) levels. Among these changes, raised IDL has been shown as an independent risk factor for atherosclerosis in hemodialysis patients. There are a limited number of studies reporting pharmacological approaches to IDL reduction in a uremic population. METHODS: We therefore summarize the effects of lipid-lowering drugs on IDL levels in patients with chronic renal failure treated by hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). RESULTS: First, a nicotinic acid analog niceritrol was given to hemodialysis patients. The drug increased HDL-cholesterol by 11%, but the reductions in VLDL-, IDL- and LDL-cholesterol were not significant. Second, CAPD patients were treated with a fibric acid derivative clinofibrate, which was excreted mainly into bile unlike other drugs in this class. The fibrate resulted in a remarkable reduction in VLDL-triglycerides, although it did not reduce IDL-cholesterol. Finally, an HMG-CoA reductase inhibitor (statin) pravastatin was used in HD and CAPD patients. Pravastatin reduced IDL- and LDL-cholesterol to the same extent (by 31%). None of these treatments caused serious adverse effects. CONCLUSIONS: We propose that IDL is an important target in the management of uremic dyslipidemia. To date, statins have been shown to be suitable for this purpose, although it remains to be clarified whether such an intervention reduces the risk for atherosclerotic vascular events in the uremic population.

Cholesterol, LDL↗

Bactericidal activity of manganese and iodide ions against Staphylococcus aureus: a possible treatment for acute atopic dermatitis.

We reported previously that balneotherapy using Kusatsu hot-spring water is useful for controlling the skin symptoms of acute flares/exacerbations of refractory cases of atopic dermatitis. As Staphylococcus aureus on the skin surface decreased in number or disappeared after balneotherapy, the hot-spring water was suspected to act against the microorganism. The hot-spring water showed strong bactericidal activity against S. aureus in vitro. In order to clarify the mechanism further, the bactericidal activity of the hot-spring water was examined by adding back cations and anions in same concentrations as those in the original hot-spring water, one at a time to cation- and anion-exchanged hot-spring water. The findings clearly demonstrated that the bactericidal activity was expressed by manganese and iodide ions in acidic conditions (pH 2.0-3.0). Thus, the probable mechanism for the improvement of skin manifestations through Kusatsu balneotherapy is the bactericidal activity of the hot-spring water against S. aureus. When added to water acidified with sulphuric acid (pH 2.0-3.0) a synergistic effect of the 2 ions was observed, so that an anti-staphylococcal effect was obtained even at low concentrations (1 mg/kg). Acidic solutions containing manganese and iodide ions may thus be clinically useful for treating skin conditions caused by S. aureus.

Acute Disease↗

Inhibition of galactose-induced cataractogenesis by troglitazone, a new antidiabetic drug with an antioxidant property, in rat lens culture.

Troglitazone is a new antidiabetic drug with a combined chemical structure of thiazolidinedione and alpha-tocopherol like structure (chroman ring). We evaluated the effect oftroglitazone on the morphological and biochemical changes in rat lenses cultured with galactose. Culturing in 30 mM galactose medium for 48 hrs resulted in vacuole formation in the cortex of lens equator (early phase of cataract). A significant amount of galactitol accumulation and lipid peroxide formation were also observed in lenses exposed to galactose. These morphological and biochemical changes associated with galactose were inhibited by 2 or 20 microM troglitazone present in the galactose medium. These results confirm the previous finding that troglitazone delayed the formation of cataract in rats fed a galactose diet. The anticataract effect of troglitazone was discussed in terms of antioxidant property of the drug.

Aldehyde Reductase↗

Evaluation of ectopic pregnancy by magnetic resonance imaging.

Patients (n = 37) suspected of ectopic pregnancy were prospectively evaluated with magnetic resonance (MR) imaging to assess the capability of MR imaging in the diagnosis of ectopic pregnancy. Five levels of confidence were defined: diagnostic, suspicious, equivocal, questionable, and negative. Tubal wall enhancement and presence of tubal haematoma or gestational sac-like structure were considered diagnostic findings. There were 21 diagnostic, two suspicious, eight equivocal, and six negative findings. MR findings were compared with the surgical findings in 18 patients. Surgical confirmation was obtained in 12 diagnostic, two suspicious, and four equivocal studies. Using the MR diagnostic criteria for tubal pregnancy, MR had 12 true positive, three true negative, three false negative, and no false positive results for the diagnosis of tubal pregnancy. Retrospective analysis of the signal intensity of haematoma and ascites was performed for these 18 surgically confirmed cases. The predominant signal intensity of tubal haematoma was an intermediate signal on T1-weighted image (WI) and a low signal on T2WI. Ascites showed signal intensity higher than that of urine on T1WI in 100% of 13 cases. In conclusion, MR imaging with use of intravenous contrast material allows a specific diagnosis of tubal pregnancy, recognizing tubal wall enhancement and fresh tubal haematoma.

Adult↗

National average for the process of radiation therapy in Japan by Patterns of Care Study.

BACKGROUND: A nationwide effort is in progress to establish the actual state of radiotherapy and its quality assurance (QA) in Japan by using the Patterns of Care Study (PCS). In this study, national averages are calculated with a limited number of patients. A calculation program for national averages was prepared and applied to the radiotherapeutic processes used for esophageal cancer patients entered in the PCS. METHODS: The calculation program for national averages, which were revised on the basis of differences between individual facilities and institutional strata, was developed in accordance with Sedransk's equation for the original PCS in the USA. National averages for several aspects concerning the sampled patients who had esophageal cancer between 1992 and 1994 were calculated with these procedures. Data for facilities and stratification of institution were simulated from a national structure survey of radiation oncology in 1990. RESULTS: Values of the national average by Sedransk's equation were different from those of the simple sample average. There were significant differences in radiotherapeutic processes among stratification of institutions. For esophageal cancer, national averages were 0.129 for applications of endoscopic ultrasound, 0.599 for 'all fields treated each day' and 0.088 for application of brachytherapy. CONCLUSION: National averages for radiotherapy could be calculated. The values obtained in this PCS will be a useful measure for future QA in radiation oncology and in other specialties in Japan.

Esophageal Neoplasms↗

CD9 is expressed in extravillous trophoblasts in association with integrin alpha3 and integrin alpha5.

The CD9 molecule is a 24-27 kDa cell surface glycoprotein, which may be related to Schwann cell migration and adhesion. In this study, we examined the expression of CD9 in human extravillous trophoblasts, which invade into the endometrium during implantation and placentation. CD9 was detected immunohistochemically on the extravillous trophoblasts in the cell columns of first trimester placentae, but not on villous trophoblasts. In the second and third trimester, CD9 was highly expressed on the extravillous trophoblasts in the basal plate of placentae, and in the chorion laeve in the fetal membrane of term placentae. The molecular mass of CD9 in the chorion laeve was shown to be 27 kDa by Western blotting. The mRNA of CD9 was also detected in the chorion laeve by reverse transcription-polymerase chain reaction (RT-PCR). Proteins were purified from chorion laeve by affinity chromatography with anti-integrin alpha3 and alpha5 monoclonal antibodies and Western blotting, revealed that CD9 was associated with both integrins. These findings indicate that CD9 is a differentiation-related molecule present in the extravillous trophoblasts. Since it is associated with integrin alpha5 which has been proposed to regulate trophoblast invasion, CD9 may be implicated in trophoblast invasion at the feto-maternal interface.

Antigens, CD↗

CD9 is involved in invasion of human trophoblast-like choriocarcinoma cell line, BeWo cells.

The CD9 molecule is expressed on human extravillous trophoblasts, which invade the endometrium during implantation and placentation. To elucidate the role of CD9 in trophoblastic function, we investigated the expression of CD9 protein and mRNA in BeWo cells, a human trophoblast-like choriocarcinoma cell line, using immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). When BeWo cells were cultured with anti-CD9 monoclonal antibodies (mAb), their invasion through the extracellular matrices was significantly enhanced in a dose-dependent manner. Cell proliferation and human chorionic gonadotrophin production were unaffected. On the other hand, culture in the presence of mAb against integrins alpha3, alpha5 and beta1, which partially block the interaction with the extracellular matrices, inhibited BeWo cell invasion. Anti-CD9 monoclonal antibody had a stimulatory effect on BeWo cell invasion in the presence of anti-integrin alpha3 antibody. In contrast, it had no effect in the presence of mAb against integrins alpha5 and beta1, which were also highly expressed on BeWo cells. These findings suggest that CD9 has a function connected with the invasive properties of BeWo cells, which is partially mediated by integrin alpha5beta1. This may relate to the involvement of CD9 in trophoblastic invasion.

Antibodies, Monoclonal↗

Human granulosa cells express integrin alpha2 and collagen type IV: possible involvement of collagen type IV in granulosa cell luteinization.

Previously, it has been shown that integrin alpha6beta1 expressed on human granulosa cells regulates luteinization in co-operation with its ligand, laminin. In this study, integrin alpha2 was immunohistochemically demonstrated to be expressed on granulosa and large luteal cells. It was also detected on luteinizing theca interna cells after ovulation. Immunoreactive collagen type IV, which is one of the ligands for integrin alpha2beta1, was detected around granulosa cells in the pre-ovulatory follicles and its expression was rapidly increased during ovulation. By flow cytometry, collagen type IV was detected on the cell surface of luteinizing granulosa cells isolated from pre-ovulatory follicles, confirming the physiological interaction between granulosa cells and collagen type IV. Collagen type IV in follicular fluid was positively related with progesterone concentration. In 4-day cultures of granulosa cells, collagen type IV in the media was significantly increased by human chorionic gonadotrophin (HCG). The progesterone production was significantly attenuated when granulosa cells were cultured on collagen type IV-coated dishes, suggesting that collagen type IV suppresses granulosa cell luteinization. These findings show that collagen type IV, a ligand for integrin alpha2beta1, is rapidly produced around luteinizing granulosa cells during ovulation, probably under the control of luteinizing hormone (LH) and suggest that collagen type IV is a new parameter and/or regulator of granulosa cell luteinization in the periovulatory phases.

Antigens, CD↗

The guanosine binding mechanism of the Tetrahymena group I intron.

The Tetrahymena group I intron catalyzes self-splicing through two consecutive transesterification reactions, using a single guanosine-binding site (GBS). In this study, we constructed a model RNA that contains the GBS and a conserved guanosine nucleotide at the 3'-terminus of the intron (omegaG). We determined by NMR the solution structure of this model RNA, and revealed the guanosine binding mechanism of the group I intron. The G22 residue, corresponding to omegaG, participates in a base triple, G22 xx G3 x C12, hydrogen-bonding to the major groove edge of the Watson-Crick G3 x C12 pair. The G22 residue also interacts with A2, which is semi-conserved in all sequenced group I introns.

Animals↗

Crystal structures of wild-type and mutant plastocyanins from a higher plant, Silene.

Plastocyanin functions as an electron carrier between the cytochrome b6f complex and photosystem I. The crystal structures of the wild-type and E43K/D44K double mutant from the higher plant, Silene, have been determined at 2.0 and 1.75 A resolution, respectively. The wild-type plastocyanin comprises two monomers per asymmetric unit, one of which shows the unusually great distance between the copper ion and the Ndelta1 atom of H87 because of the hydrogen bond network formation between H87 and symmetry-related G10. The root mean square deviation for Ca atoms between the wild-type and mutant plastocyanins is 0.44 A, however, the electrostatic potential maps of their molecular surfaces are remarkably different. The low electron-transfer rate in the E43K/D44K mutant results from the hindrance of electrostatic interactions, not from the structural change due to the mutation.

Copper↗