Biomedical subjects

T Ohishi

Publications and source records attributed to T Ohishi.

At least 19 recordsLinked to original sources

PubMed2005

Cyclophosphamide and low-dose prednisolone in idiopathic pulmonary fibrosis and fibrosing nonspecific interstitial pneumonia.

The present study compared the efficacy of cyclophosphamide combined with low-dose prednisolone in the treatment of idiopathic pulmonary fibrosis (IPF) with efficacy in idiopathic fibrosing nonspecific interstitial pneumonia fibrosing (NSIP). A total of 27 patients with IPF and 12 patients with fibrosing NSIP were included in this study. All patients had undergone surgical lung biopsy. The diagnoses were made based on clinical, radiological and pathological findings. All patients were treated with intermittent pulse therapy with methylprednisolone for 4 weeks, followed by cyclophosphamide with low-dose prednisolone. According to pulmonary function tests, four of 27 patients with IPF had improved, 22 remained unchanged, and one had worsened at the completion of pulse therapy. After 1 yr of combination therapy, four of 27 patients had improved, 14 remained unchanged, and nine had worsened. After pulse therapy, four of 12 patients with fibrosing NSIP had improved, and eight remained unchanged. After 1 yr of combination therapy, eight of 12 patients had improved, four remained unchanged, and none had worsened. Median survival of IPF patients was 4.1 yrs, which is significantly worse than that of fibrosing NSIP patients. In conclusion, patients with fibrosing nonspecific interstitial pneumonia had a more favourable response to combination therapy and a better survival than those with idiopathic pulmonary fibrosis.

Anti-Inflammatory Agents↗

PubMed2002

Effects of long-term administration of sulindac on APC mRNA and apoptosis in colons of rats treated with azoxymethane.

PURPOSE: Non-steroidal anti-inflammatory drugs, including sulindac, have been shown to exhibit anti-colon cancer activity; however, the detailed mechanisms concerning continuous long-term administration are still unclear. Therefore, we examined the anti-colon carcinogenesis effects of sulindac after prolonged administration. METHODS: Administration of AOM, a colon-specific carcinogen, induced colonic preneoplastic lesions, which can progress to carcinomas about 40-50 weeks after AOM administration. We studied the effects of sulindac on the incidence of preneoplastic lesions, proliferative activity of colonic cells (AgNORs), tumor suppressor adenomatous polyposis coli (APC) gene expression, and apoptosis using AOM-treated rat colon mucosa at 4 weeks and 40 weeks (early and late stage of colon carcinogenesis, respectively). RESULTS: Sulindac suppressed the development of preneoplastic lesions induced by AOM at 4 weeks and 40 weeks by about 50% ( P<0.01); the proliferative activity of colonic cells increased by AOM was suppressed almost completely. Furthermore, APC expression was significantly increased by sulindac at both the early and late stages ( P<0.01). However, apoptosis was clearly increased at the early stage ( P<0.01), but not at the late stage. CONCLUSIONS: APC overexpression induced by sulindac can suppress colon carcinogenesis at both the early and late stages, but apoptosis might work as one of anti-cancer mechanisms at the early stage of colon carcinogenesis.

Adenomatous Polyposis Coli Protein↗

PubMed2001

Th1 and Th2 cytokines differentially regulate the transformation of Kupffer cells into multinucleated giant cells but similarly enhance the Kupffer cell-induced hepatic stellate cell proliferation.

To investigate the effects of T-helper cytokines on Kupffer cells (KCs), the effects of interferon-gamma (IFN-gamma; Th1 cytokine) and interleukin-4 (IL-4; Th2 cytokine) on KC morphology and their role in modulating the growth of hepatic stellate cells (HSCs) were examined. Fluorescence microscopic and electron microscopic data demonstrated that IL-4 transforms rat KCs into multinucleated giant cells (MGCs) in vitro. This transformation was inhibited by the addition of anti-ICAM-1 and anti-CD18 monoclonal antibodies. In addition, IL-4-induced KC transformation was suppressed by the presence of IFN-gamma. The formation of mouse hepatic MGCs was also demonstrated in vivo by the intraperitoneal injection of recombinant mouse IL-4. Although the presence of MGCs was found in all five out of five livers from IL-4-treated Th2-dominant BALB/c mice, but it was in only two out of five livers from IL-4-treated Th1-dominant C57BL/6 mice. In addition, fewer MGCs were found in the liver of C57BL/6 mice. In contrast, IFN-gamma treatment did not form hepatic MGCs in mice at all. The growth of HSCs in vitro was significantly increased by the addition of culture supernatant from lipopolysaccharide-stimulated rat KCs. Pretreatment of the KCs with either IFN-gamma or IL-4 further enhanced the growth stimulation. These results suggest that IFN-gamma and IL-4 affect KC morphology differently, but that both Th1 and Th2 cytokines play a similar role in the modulation of HSC growth by Kupffer cells in the presence of lipopolysaccharide.

Journal Article↗

PubMed2001

Anti-fibrogenic effect of an angiotensin converting enzyme inhibitor on chronic carbon tetrachloride-induced hepatic fibrosis in rats.

The tissue renin-angiotensin system has recently been demonstrated to reduce fibrogenesis in various organs. However, little has been clarified regarding its role in hepatic fibrosis. The purpose of this study was to investigate the effect of angiotensin-converting enzyme inhibitors on liver fibrogenesis induced in rats by low-dose chronic carbon tetrachloride administration. We used lisinopril that is absorbed in its active form and not metabolized in the liver to avoid any influence by the administration of the chemical. Carbon tetrachloride was administered twice a week i.p. Twelve and 24 weeks after the start of treatment, expanded periportal fibrosis or portal-portal bridgings and severe fat deposition were observed in the rats treated with carbon tetrachloride alone, and these findings were significantly reduced with the simultaneous treatment with lisinopril. The hydroxyproline content of the liver was significantly lower in the lisinopril-treated group. Angiotensin II up-regulated mRNA of pro alpha (I) collagen and transforming growth factor-beta in isolated hepatic stellate cells. These results suggest that the local tissue renin-angiotensin system plays a role in rat hepatic fibrogenesis induced by chronic carbon tetrachloride administration and that hepatic fibrogenesis is significantly reduced by ACE inhibitors.

Journal Article↗

PubMed2001

Effect of vitamin K and/or D on undercarboxylated and intact osteocalcin in osteoporotic patients with vertebral or hip fractures.

OBJECTIVE: To examine serum undercarboxylated osteocalcin (OC) with application of an ELISA in normal women and in osteoporotic patients with vertebral fractures or hip fractures, and to investigate the effects of vitamin K and/or D treatment on undercarboxylated OC and intact OC in vertebral fractures. PATIENTS: They were 43 premenopausal (PRE) and 48 postmenopausal healthy females (POST), 89 osteoporotic patients with vertebral fractures (VX) and, 24 patients with hip fracture (HX). MEASUREMENTS: Intact OC was measured by an IRMA and undercarboxylated OC was measured by an ELISA. RESULTS: Intact osteocalcin was significantly higher in POST and VX than in PRE, and was significantly lower in HX than in POST and VX. Undercarboxylated OC tended to be higher in POST, VX and HX than in PRE, but not significantly. The ratio of undercarboxylated OC to intact OC was significantly higher in HX than in POST and in VX. After 4 weeks treatment with K, D, and K + D to 56 VX, undercarboxylated OC decreased significantly in the groups with K and K + D. Intact OC tended to increase slightly in the groups given K, D, K + D, but not significantly so. Vitamin K and vitamin K + D markedly decreased the ratio of undercarboxylated/intact OC to approximately 80%. On the other hand, vitamin D did not decrease that ratio. CONCLUSIONS: There was a disproportion of undercarboxylated osteocalcin to intact osteocalcin between postmenopausal women and osteoporotic patients with vertebral fractures or hip fractures. Vitamin K did decrease undercarboxylated osteocalcin, vitamin D did not change undercarboxylated osteocalcin, and vitamin D did not enhance the effect of vitamin K on undercarboxylated osteocalcin.

Adult↗

PubMed2001

[A clinical study on patients detected Pasteurella multocida from sputum].

We reported ten cases, (four female and six male), whose sputum cultures positive for Pasteurella multocida from 1990 to 2000. In the past eleven years increasing numbers of cases have appeared in our hospital. The majority of the cases with P. multocida possessed some underlying pulmonary diseases (seven cases, 70%), inactive lung tuberculosis or bronchiectasis. There were compromised hosts such as high ages person, steroids dependent person and diabetes mellitus patients. P. multocida was almost susceptible to antibioticus (penicillin and cephalosporins), although some erythromycin resistant strains were identified. The cats' oral cavities in our two cases were cultured and P. multocida were isolated. In our survey the prevalence of this organism is as high as 85% in cats. Our data suggests that patients who are in the high infection risk category are easily infected to P. multocida.

Adolescent↗

PubMed2001

Molecular cloning of the platelet P2T(AC) ADP receptor: pharmacological comparison with another ADP receptor, the P2Y(1) receptor.

Platelet activation plays an essential role in thrombosis. ADP-induced platelet aggregation is mediated by two distinct G protein-coupled ADP receptors, Gq-linked P2Y(1), and Gi-linked P2T(AC), which has not been cloned. The cDNA encoding a novel G protein-coupled receptor, termed HORK3, was isolated. The HORK3 gene and P2Y(1) gene were mapped to chromosome 3q21-q25. HORK3, when transfected in the rat glioma cell subline (C6-15), responded to 2-methylthio-ADP (2MeSADP) (EC(50) = 0.08 nM) and ADP (EC(50) = 42 nM) with inhibition of forskolin-stimulated cAMP accumulation. 2MeSADP (EC(50) = 1.3 nM) and ADP (EC(50) = 18 nM) also induced intracellular calcium mobilization in P2Y(1)-expressing cells. These results show that HORK3 is a Gi/o-coupled receptor and that its natural ligand is ADP. AR-C69931 MX and 2MeSAMP, P2T(AC) antagonists, selectively inhibited 2MeSADP-induced adenylyl cyclase inhibition in HORK3-expressing cells. On the other hand, A3P5PS, a P2Y(1) antagonist, blocked only 2MeSADP-induced calcium mobilization in P2Y(1)-expressing cells. HORK3 mRNA was detected in human platelets and the expression level of HORK3 was equivalent to that of P2Y(1). These observations indicate that HORK3 has the characteristics of the proposed P2T(AC) receptor. We have also determined that [(3)H]2MeSADP binds to cloned HORK3 and P2Y(1). Competition binding experiments revealed a similarity in the rank orders of potency of agonists and the selectivity of antagonists as obtained in the functional assay. These results support the view that P2Y(1) functions as a high-affinity ADP receptor and P2T(AC) as a low-affinity ADP receptor in platelets.

Adenosine Triphosphate↗

PubMed2001

[Clinical application of metabolic bone markers for fracture - effects of fracture on metabolic bone markers -].

The process of fracture healing can be divided into three distinct stages - inflammatory, reparative and remodeling stages. The changes of bone formation and bone resorption in the process of fracture healing are expected to be more dynamic than those changes which occur in the remodeling cycle alone because of aging. Bone formation and bone resorption markers increased 1 or 2 weeks after fracture. Bone resorption markers returned to the baseline level at 24 weeks after fracture, while values of bone formation marker were still higher compared to the baseline level at 24 weeks after fracture. It is suggested that bone metabolism is still activated at 24 weeks after fracture. In the acute phase after fracture, many factors such as bed rest, skin incision, intramedullay reaming during operation, could modify the values of bone resorption and bone formation markers. Therefore, clinical application of metabolic bone markers for fracture might be useful in the remodeling stage after fracture.

English Abstract↗

PubMed2000

Molecular cloning and characterization of another leukotriene B4 receptor.

Leukotriene B(4) is a potent lipid mediator known to be implicated mainly in inflammatory actions. Previous pharmacological studies indicated the existence of only one class of G protein-coupled receptor for leukotriene B(4), for which a candidate gene, namely BLT, had been identified. Here we report the isolation of another gene encoding a functional G protein-coupled receptor for leukotriene B(4), named JULF2. JULF2 is a novel G protein-coupled receptor of 358 amino acids that shares 36.6% amino acid identity with human BLT. According to genomic information, the JULF2 gene is located on the chromosome 14, about 4 kilobases upstream of the BLT gene. During screening of endogenous ligands for JULF2, we found that leukotriene B(4) induced inhibition of forskolin-stimulated cAMP accumulation in Chinese hamster ovary cells, stably expressing JULF2. Additionally, Chinese hamster ovary cells expressing exogenous JULF2 showed chemotactic responses with leukotriene B(4) in a pertussis toxin-sensitive manner. A large amount of JULF2 mRNA was detected in the human spleen and the peripheral blood leukocytes. Furthermore, JULF2 mRNA was expressed in mononuclear lymphocytes, in which BLT mRNA was barely detected. The discovery of this second leukotriene B(4) receptor will eventually lead to a better understanding of the classification of leukotriene B(4) receptors and reconsideration of the pathophysiological role of leukotriene B(4).

Amino Acid Sequence↗

PubMed2000

The molecular characterization and tissue distribution of the human cysteinyl leukotriene CysLT(2) receptor.

Cysteinyl leukotrienes (CysLTs), slow-reacting substances of anaphylaxis, are lipid mediators known to possess potent proinflammatory action. Pharmacological studies using CysLTs indicate that at least two classes of G protein-coupled receptors (GPCRs), named CysLT(1) and CysLT(2), exist; the former is sensitive and the latter is resistant to the CysLT(1) antagonists currently used to treat asthma. Although the CysLT(1) receptor gene has been recently cloned, the molecular identity of the CysLT(2) receptor has remained elusive. Here we show that the pharmacological profile of an orphan GPCR (PSEC0146) is consistent with that of the CysLT(2) receptor. In human embryonic kidney 293 cells that express the PSEC0146 cDNA, leukotriene C(4) (LTC(4)) and leukotriene D(4) (LTD(4)) induce equal increases in intracellular calcium mobilization; these increases are not affected by CysLT(1) antagonists. Additionally, [(3)H]LTC(4) specifically binds to membranes from COS-1 cells transiently transfected with PSEC0146. Large amounts of the PSEC0146 mRNA are found in human heart, placenta, spleen, and peripheral blood leukocytes but not in the lung and the trachea. Pharmacological feature and expression studies will eventually lead to a better understanding of the classification of CysLT receptors, possibly leading to a reconsideration of the pathological and physiological role of CysLTs.

Animals↗

PubMed2000

An evolutionarily conserved G-protein coupled receptor family, SREB, expressed in the central nervous system.

We report here a novel family of G-protein coupled receptor (GPCR) which is extraordinarily conserved among vertebrate species. This family, designated SREB (Super Conserved Receptor Expressed in Brain), consists of at least three members, termed SREB1, SREB2, and SREB3. SREB members share 52-63% amino acid identity with each other and show relatively high similarity to previously known amine amine GPCRs (approximately 25% identity). Amino acid sequence identity between human and rat orthologues is 97% for SREB1 and 99% for SREB3, while the SREB2 sequence is surprisingly completely identical between the species. Furthermore, amino acid sequence of zebrafish SREB2 and SREB3 are 94 and 78% identical to mammal orthologues. Northern blot analysis revealed that SREB members are predominantly expressed in the brain regions and genital organs. Radiation hybrid analysis localized SREB1, SREB2, and SREB3 genes to different human chromosomes, namely 3p21-p14, 7q31 and Xp11, respectively. The high sequence conservation and abundant expression in the central nervous system suggest the existence of undiscovered fundamental neuronal systems consisting of SREB family members and their endogenous ligand(s).

Amino Acid Sequence↗

PubMed2000

Bone mineral density and bone turnover in patients with knee osteoarthritis compared with generalized osteoarthritis.

The aim of this study was to investigate bone mineral density (BMD) and bone turnover in patients with primary knee osteoarthritis (KOA) and to compare them with generalized OA (GOA) and nonGOA patients. A total of 88 postmenopausal primary KOA patients were studied. OA was graded by using knee radiographs. BMD of the lumber spine, femur, and radius, and biochemical markers of bone turnover, pyridinoline (Pyr), deoxypyridinoline (Dpyr), CTx, and osteocalcin were compared among each grade. BMD was also compared with 88 normal controls who were age and weight-matched. In 88 KOA patients, 56 were divided into 28 GOA and 28 non-GOA groups by grading hand radiographs. BMD and biochemical markers were compared between GOA and non-GOA. KOA patients had higher BMD at several skeletal sites compared with age- and weight-matched normals. A significant difference of BMD between each grade was observed between grades 0-1 and 3 (0.774+/-0.143 versus 0.940+/-0.185 g/cm(2), P<0.001), grades 2 and 3 (0.781+/-0.125 versus 0.940+/-0.185 g/cm(2), P<0.01) in the spine, and between grades 0-1 and 3 (0.505+/-0.100 versus 0.564+/-0.127 g/cm(2), P<0.05) in the trochanter. A significant difference of biochemical bone markers was observed between grades 0-1 and 3 (P<0.05) and between grades 2 and 3 (P<0.05) in Pyr and grades 0-1 and 3 (P<0.05) and between grades 1 and 4 (P<0.05) in Dpyr, but not in osteocalcin and CTx. GOA patients had higher BMD of the spine (0.902+/-0.175 versus 0.747+/-0.138 g/cm(2), P<0.01), trochanter (0.535+/-0.107 versus 0.480+/-0.107 g/cm(2), P<0.05), and one-third of the radius (0.526+/-0.068 versus 0.472+/-0. 089 g/cm(2), P<0.05) and had significantly higher biochemical markers in Pyr and Dpyr than non-GOA patients. It is concluded that KOA patients had higher BMD at several skeletal sites. Biochemical bone markers were influenced by some degree of cartilage damage in OA patients. This tendency was stronger in GOA patients than in non-GOA patients.

Aged↗

PubMed2000

Evaluation of isolated fractures of the greater trochanter with magnetic resonance imaging.

The diagnosis of an isolated fracture of the greater trochanter can be done on routine radiographs, but this may not be the whole story. We evaluated fractures of the greater trochanter of the femur by magnetic resonance imaging (MRI). MR images were obtained within 5 days of the time of clinical presentation. Coronal images were performed on T1- and T2-weighted spin-echo images. Eight elderly patients who were diagnosed as having a greater trochanter fracture on standard radiographs underwent MRI. Three were men aged 62-76 (mean 63.4) years, and five were women aged 80-101 (mean 88.6) years. MRI showed that in seven of the eight cases, the fracture line was observed leading from the greater trochanter towards other trochanter regions. In only one case was the fracture limited to the greater trochanter and corresponded to the line observed on the standard radiographs. We suggest that in cases of greater trochanter fracture with somewhat severe symptoms, MRI should be performed in order to discover the appropriate diagnosis and treatment.

Accidental Falls↗

PubMed2000

The efficacy of biochemical markers in patients with ossification of posterior longitudinal ligament of the spine.

STUDY DESIGN: Serum levels of carboxyterminal propeptide of type I collagen (PICP), osteocalcin (OC), carboxyterminal telopeptide of type I collagen (ICTP) and urinary levels of pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured in patients with ossification of posterior longitudinal ligament of the spine (OPLL) and age-matched control subjects. OBJECTIVES: To evaluate the efficacy of these biochemical markers of the patients with OPLL. SETTING: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. METHODS: Spot urine and blood samples were obtained from 20 healthy males aged 45 - 78 (mean+/-SD; 63. 0+/-11.5) and 22 male patients with OPLL aged 46 - 77 (mean+/-SD; 59. 9+/-8.8), and serum levels of PICP, OC, ICTP and urinary levels of Pyr and Dpyr were measured. RESULTS: There were no significant difference in age, serum PICP, OC, ICTP, urinary Pyr and Dpyr levels between OPLL and control group. CONCLUSION: Neither bone formation nor bone resorption was accelerated in the patients with OPLL.

Aged↗

PubMed2000

Scapholunate dissociation caused by gouty arthritis of the wrist. Case report.

Gouty arthritis of the wrist is rare, and may be associated with scapholunate dissociation. To our knowledge, only two cases have been reported so far. In this report, we describe a 40-year-old patient with scapholunate dissociation caused by acute gouty arthritis of the wrist. His clinical findings and radiographs mimicked infectious arthritis or osteomyelitis of the carpal bones.

Adult↗

PubMed2000

Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fractures. Contact Ultrasound Bone Analyzer.

The purpose of this study was to assess the ultrasound (US) parameters measured by Contact Ultrasound Bone Analyser (CUBA) clinical system for discriminating the subjects with vertebral fractures from those without vertebral fractures. The subjects consisted of 114 postmenopausal women over age 50 (mean +/- SD: 72.2 +/- 8.7). Seventy-three had vertebral fractures (fracture group) and 41 had no vertebral fractures (control group). Values of all US parameters and bone mineral density (BMD) in the fracture group were significantly lower than those in the control group, even after adjusting for age. Areas under the receiver operating characteristic (ROC) curve was 0.768 +/- 0.056 (mean +/- SE) for broadband ultrasound attenuation (BUA) 0.828 +/- 0.045 for velocity of sound (VOS), 0.707 +/- 0.058 for lumbar spine, 0.872 +/- 0.050 for femur neck, 0.790 +/- 0.050 for trochanter, and 0.695 +/- 0.060 for Ward's triangle. There were no significant differences among the areas under the ROC curves in BUA, VOS, lumbar spine, femur neck, trochanter, and Ward's triangle. US parameters (BUA and VOS) had the same discriminatory power as spine and hip BMD for evaluating the vertebral fracture risk. As far as disadvantages of the use of BMD measurement against US measurement, US measurement is potentially useful for screening of vertebral fractures. However, the bias concerning the propotion of the number of patients with or without vertebral fractures could not be neglected in this study.

Aged↗

PubMed2000

Biochemical markers and bone mineral density in patients with hip fractures in men.

The purpose of this study was to determine whether males with hip fractures have associated decreased gonadal function. Second void urine and serum samples were obtained from 25 male hip fracture patients (mean age+/-SD, 78.5+/-5.9 years) and 19 age- and gender-matched controls (77.6+/-6.2 years). Serum levels of luteinizing hormone (LH), total testosterone (Te), total estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), 1,25(OH)2D3, N-mid osteocalcin (OC(N-mid)), type I collagen degradation products (S-CTx) and urinary levels of pyridinoline (Pyr), deoxypyridinoline (Dpyr) and type I collagen degradation products (U-CTx) were measured. Bone mineral density (BMD) of the L2-4 spine, femoral neck, trochanter, Ward's triangle, distal one third portion of the radius and ultradistal radius were also measured in the fracture group. Serum levels of LH, E2, Te, DHEAS, 1,25(OH)2D3 and OCN-mid in the fracture group were not statistically different from those in the control group. Levels of urinary Pyr, CTx and S-CTx in the fracture group increased significantly compared with those in the control group. In the fracture group, serum levels of Te correlated positively with distal one third portion of the radius BMD and ultradistal radius BMD. U-CTx and S-CTx correlated negatively with all the BMD measurement sites in the hip region and with the radius BMD. An imbalance between bone resorption and bone formation was evident in male hip fracture patients. However, male patients with hip fractures did not show associated decreased gonadal function in this study.

Aged↗

PubMed1999

Polymorphism in RANTES chemokine promoter affects HIV-1 disease progression.

RANTES (regulated on activation normal T cell expressed and secreted) is one of the natural ligands for the chemokine receptor CCR5 and potently suppresses in vitro replication of the R5 strains of HIV-1, which use CCR5 as a coreceptor. Previous studies showed that peripheral blood mononuclear cells or CD4(+) lymphocytes obtained from different individuals had wide variations in their ability to secrete RANTES. These findings prompted us to analyze the upstream noncoding region of the RANTES gene, which contains cis-acting elements involved in RANTES promoter activity, in 272 HIV-1-infected and 193 non-HIV-1-infected individuals in Japan. Our results showed that there were two polymorphic positions, one of which was associated with reduced CD4(+) lymphocyte depletion rates during untreated periods in HIV-1-infected individuals. This mutation, RANTES-28G, occurred at an allele frequency of approximately 17% in the non-HIV-1-infected Japanese population and exerted no influence on the incidence of HIV-1 infection. Functional analyses of RANTES promoter activity indicated that the RANTES-28G mutation increases transcription of the RANTES gene. Taken together, these data suggest that the RANTES-28G mutation increases RANTES expression in HIV-1-infected individuals and thus delays the progression of the HIV-1 disease.

Base Sequence↗