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Biomedical subjects

T Kamimura

Publications and source records attributed to T Kamimura.

At least 19 recordsLinked to original sources
PubMed2006

Urine cartilage oligomeric matrix protein (COMP) measurement is useful in discriminating the osteoarthritic Thoroughbreds.

OBJECTIVE: To quantify the urinary concentration of cartilage oligomeric matrix protein (COMP), and to evaluate the relationship between urinary COMP concentration and the catabolic activity of synovial fluid (SF) in diseased horses. METHODS: COMP in horse urine was detected by immunoblotting with a monoclonal antibody (mAb; 14G4) raised against equine COMP from articular cartilage. Urine and serum samples were obtained from 83 Thoroughbred horses with aseptic joint diseases (AJD, 79 horses) or septic joint diseases (SJD, four horses) at the time of anesthesia induction, and samples of SF were obtained during surgery. Control samples of urine (n=111) were collected from normal horses free of any orthopedic diseases after they had been racing. COMP concentration was determined in all samples using inhibition enzyme-linked immunosorbent assay (ELISA) with mAb 14G4. SF samples were also used for the quantification of gelatinase activity. RESULTS: Positive bands of COMP fragments were determined on the immunoblots with mAb 14G4. The urinary COMP concentrations in AJD and SJD horses (1.02+/-0.75 and 1.55+/-1.17 microg/100mg creatinine, respectively) were significantly higher than normal (0.57+/-0.29 microg/100mg creatinine). In 55 horses with fractures in the AJD group there was a logarithmic relationship (r=-0.45, P<0.001) between the urinary and SF COMP measurements, while the urinary COMP level was positively correlated with matrix metalloproteinase (MMP)-2 and -9 activities (r=0.30, P<0.05 and r=0.51, P<0.001, respectively) in SF. CONCLUSIONS: The urinary COMP assay with mAb 14G4 is useful for discriminating horses with osteoarthritis. The higher COMP levels in urine from such horses would be indicative of enhanced proteolytic activity, in addition to the increased COMP levels in the diseased joints.

Animals↗
PubMed2006

Repeated massive tongue swelling due to the combined use of estramustine phosphate and angiotensin-converting enzyme inhibitor.

A 70-year-old man presenting with a chief complaint of tongue swelling had been diagnosed with prostate cancer 1 year earlier. He had been on an oral angiotensin-converting enzyme inhibitor (ACE) inhibitor for hypertension for 20 years. Two months before the first of 4 episodes of tongue swelling within a period of 40 days, he had been prescribed oral estramustine phosphate (EMP) for the prostate cancer. He was admitted to our hospital for the evaluation after massive swelling of the tongue and epiglottis which necessitated tracheotomy. Food allergies, allergic reactions to environmental factors, and hereditary angioneurotic edema were excluded. Massive swelling of the tongue and epiglottis disappeared completely after EMP was discontinued. We concluded that angioedema was induced by EMP used concurrently with the ACE inhibitor.

Aged↗
PubMed2005

FLT3 mutations in normal karyotype acute myeloid leukemia in first complete remission treated with autologous peripheral blood stem cell transplantation.

We retrospectively analysed the significance of FLT3 mutations in patients with acute myeloid leukemia (AML) having a normal karyotype, who were treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation (auto-PBSCT). In all, 34 patients with normal karyotype AML in first complete remission receiving high-dose chemotherapy and auto-PBSCT were analysed based on the presence or absence of FLT3/ITDs and FLT3/D835. They were 16 males and 18 females and with a median age of 41.5 years. FLT3/ITDs were detected in eight of 34 patients (23.5 %), and FLT3 D835 mutations in two of 34 patients (5.9%). White blood cell count (P=0.0087), serum concentration of lactate dehydrogenase (P=0.005), and percentages of peripheral blood (P=0.0131) and bone marrow (BM) blasts (P=0.0312) were significantly higher in patients showing the FLT3 mutations. Overall survival (OS) and disease-free survival (DFS) were similar between patients with or without FLT3 mutations (5 year DFS, 67.5 vs 68.55%, P=0.819; 5 year OS, 64.81 vs 78.88%, P=0.4457, by the log-rank test). FLT3 mutations demonstrate no further prognostic impact in patients with normal karyotype AML in first CR treated with high-dose chemotherapy and auto-PBSCT. Myeloablative chemotherapy supported by auto-PBSCT may overcome any poor prognostic implications of FLT3 mutations.

Acute Disease↗
PubMed2004

The effect of valsartan on regression of left ventricular hypertrophy in type 2 diabetic patients.

AIM: The aim of the present study was to examine the effects of an angiotensin II receptor antagonist, valsartan, on echocardiographically proven left ventricular hypertrophy (LVH) in patients with type 2 diabetes. METHODS: Outpatients with type 2 diabetes mellitus were recruited at Niigata University Hospital. The left ventricular mass index (LVMI) was calculated by echocardiography. LVH was considered to be present if the LVMI was > 131 g/m(2) in males and > 100 g/m(2) in females. Patients with LVH received a low dose (40 mg/day) of valsartan for 12 months. This low dose had no clinical effect on blood pressure. RESULTS: Of the 38 patients who entered the study, 14 (36.8%) had LVH. After only 6 months of valsartan therapy, the mean LVMI decreased significantly, from 126.5 +/- 27.8 to 119.0 +/- 23.5 g/m(2) (p < 0.01 vs. baseline). Also, a significant decrease was observed after 12 months (116.5 +/- 30.9 g/m(2), p < 0.05 vs. baseline). Compared to baseline, there were no significant differences after treatment in body mass index, glycosylated haemoglobin (HbA(1c)), systolic blood pressure and diastolic blood pressure. CONCLUSIONS: In type 2 diabetic patients with LVH, treatment with a low dose of valsartan, an angiotensin II receptor antagonist, for 12 months, reduced LVMI, with no reduction in systemic blood pressure. This drug may be safely administered to type 2 diabetic patients with LVH. The long-term risk-reduction effects will have to be evaluated in further trials.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2003

Preventive effects of sequential treatment with alendronate and 1 alpha-hydroxyvitamin D3 on bone mass and strength in ovariectomized rats.

Because accumulating evidence has shown that bisphosphonates are unable to maintain their bone-sparing effects after the withdrawal of the drug, a replacement treatment is needed when bisphosphonate treatment cannot be continued for some reason. The present study investigated the preventive effects of alendronate followed by 1alpha(OH)D3 on the mass and mechanical strength of trabecular and cortical bones in ovariectomized rats. Sprague-Dawley rats were ovariectomized or sham-operated at 48 weeks of age. Ovariectomized rats treated with vehicle alone (OVX group) showed significant decreases in bone mineral density (BMD) and mechanical strength of the lumbar vertebra and the midfemur during a 20-week period after the operation as compared with sham-operated rats. These decreases were prevented by continuous treatment with alendronate (0.5 mg/kg/day, po) for 20 weeks (ALN-C group), whereas the values reverted to those of the OVX group when alendronate was withdrawn at 10 weeks (ALN-W group). The sequential treatment with alendronate and 1alpha(OH)D3 (0.05 microg/kg/day, po) for 10 weeks each (ALN --> 1alpha group) resulted in higher BMD and mechanical strength of the lumbar vertebra and the midfemur in this group than in the OVX and ALN-W groups. The increase in mechanical strength was proportional to that in BMD at both sites, suggesting that the stimulatory effects of these treatments on bone strength were due to those on bone mass. Analyses of histology, computed tomography, and biochemical markers confirmed the preventive effects of the sequential treatment. Therefore, we propose that 1alpha(OH)D3 may be a good choice to replace alendronate when alendronate treatment cannot be continued for some reason.

Aging↗
PubMed2003

Brain-derived neurotrophic factor modulates glucagon secretion from pancreatic alpha cells: its contribution to glucose metabolism.

AIM: Brain-derived neurotrophic factor (BDNF) reduces plasma glucose levels in obese db/db diabetic mice and is speculated to produce its effects via the hypothalamus, the regulatory centre of satiety and the autonomic nervous system. The potential effect of BDNF directly on peripheral endocrine organs, however, remains to be clarified. Here we report the effects of BDNF on hormonal secretion from pancreatic islets of Langerhans using their isolated culture. METHODS AND RESULTS: In an immunohistochemical study, mouse pancreatic alpha cells were stained specifically with the anti-TrkB (a specific receptor for BDNF) antibody. After 7 days culture of isolated islets of the normal mouse pancreas, 10 ng/ml BDNF decreased the secretion of glucagon per 6 h significantly less than that of the control (p = 0.016). In contrast, there were no significant changes in insulin secretion or glucagon and insulin contents in the islets cultured under the same conditions. In vivo administration of BDNF (10 mg/kg/day) to normal mice for 7 days significantly decreased their food consumption (p < 0.05). The fasting plasma glucose levels were decreased on day 7 compared with day 1 more significantly in BDNF-treated mice (p = 0.043) than in pair-fed control mice (p = 0.14). In newborn BDNF-knockout mice, fasting plasma glucose levels increased in the order of homozygote, heterozygote and wild type (p = 0.033). No apparent immunohistochemical abnormality was observed for pancreatic glucagon in the BDNF-knockout mice. CONCLUSION: These data suggest that BDNF affects glucose metabolism not only with its anorectic effect but also with modulated glucagon secretion from pancreatic alpha cells.

Animals↗
PubMed2003

Increased circulating 92 kDa matrix metalloproteinase (MMP-9) activity in exacerbations of asthma.

BACKGROUND: The 72 kDa matrix metalloproteinase 2 (MMP-2) and the 92 kDa matrix metalloproteinase 9 (MMP-9) are type IV collagenases implicated in various aspects of inflammation including accumulation of inflammatory cells, tissue injury, and development of remodelling. The role of these enzymes in the pathogenesis of asthma exacerbations is unknown. METHODS: Circulating levels of MMP-2 and MMP-9 proteins and the expression of their inhibitor, tissue inhibitor of metalloproteinase 1 (TIMP-1), were measured in 21 patients experiencing an asthma exacerbation and 21 age matched patients with stable asthma. Circulating gelatinolytic activity was compared during the asthma exacerbation and during subsequent convalescence by gelatin zymography in the same individuals. In addition, MMP-9 specific activity was quantified with a colorimetric assay which uses an artificial proenzyme containing a specific domain recognised by MMP-9 in the same paired samples. RESULTS: A significant increase in the circulating level of MMP-9 was seen in patients with an asthma exacerbation compared with patients with stable asthma (202.9 (22.0) v 107.7 (9.9) ng/ml, p=0.0003). There were no significant differences in the circulating levels of MMP-2 or TIMP-1. Gelatin zymography identified two major circulating gelatinolytic activities corresponding to MMP-2 and MMP-9, and showed that asthma exacerbations are characterised by markedly increased MMP-9 activity with no significant change in MMP-2 activity compared with the activities during convalescence in the same individuals. Direct measurement showed that MMP-9 specific activity is significantly increased during asthma exacerbations compared with subsequent convalescence (269.6 (31.7) v 170.4 (12.6) ng/ml, p=0.0099). CONCLUSIONS: Asthma exacerbations are characterised by increased circulating MMP-9 activity. This increased activity may be related to exaggerated airway inflammation and airway remodelling.

Adult↗
PubMed2002

Characterization of chemokine receptor expression and cytokine production in circulating CD4+ T cells from patients with atopic dermatitis: up-regulation of C-C chemokine receptor 4 in atopic dermatitis.

BACKGROUND: Th2 and Th1 cells have been suggested to express CCR3/CCR4 and CCR5/CXCR3, respectively. OBJECTIVE: We examined CCR3, CCR4, CCR5 and CXCR3 expression and cytokine production in peripheral blood CD4+ T cells from patients with atopic dermatitis (AD), which has been postulated to be a Th2-type cell-mediated disease, and then analysed the possible correlation between these values and the levels of several clinical parameters. METHODS: Intracellular cytokine production and chemokine receptor expression in peripheral blood CD4+ T cells from 40 AD patients and 20 sex- and age-matched healthy control subjects were studied by flow cytometry. RESULTS: The frequencies of IL-4- and IL-13-producing CD4+ T cells from patients with AD were significantly higher than those from healthy control subjects (IL-4:3.9 +/- 2.1% vs. 1.6 +/- 0.7%, P = 0.0005, IL-13:4.0 +/- 2.1% vs. 1.8 +/- 0.8%, P = 0.0023), whereas the frequencies of IL-2- and IFN-gamma-producing CD4+ T cells were significantly decreased in AD patients (IL-2:38.1 +/- 10.3% vs. 51.3 +/- 6.3%, P = 0.0003, IFN-gamma: 9.9 +/- 3.5% vs. 26.4 +/- 4.6%, P < 0.0001). The percentage of CCR4+ cells in CD4+ CD45RO+ T cells in AD patients was significantly higher than that in healthy control subjects (24.4 +/- 8.0% vs. 10.9 +/- 2.3%, P < 0.0001) and was correlated positively with the total serum IgE, serum lactic dehydrogenase (LDH) level, eosinophil number, eruption score, and IL-4 and IL-13 secretion in CD4+ T cells, and inversely with IL-2 and IFN-gamma secretion in CD4+ T cells. In contrast, CCR3 was not detected on circulating CD4+ T cells even in AD patients. On the other hand, the percentage of CCR5+ or CXCR3+ cells in CD4+ CD45RO+ T cells in AD patients was significantly decreased (CCR5:23.2 +/- 7.0% vs. 28.4 +/- 5.4%, P = 0.023, CXCR3:29.9 +/- 11.4% vs. 38.5 +/- 6.7%, P = 0.028) and was positively correlated with eruption score (P < 0.05). Multiple regression analyses showed that the percentage of CCR4 expression highly correlated with serum IgE, LDH, eosinophil number and eruption in AD patients. CONCLUSION: CCR4+ cells might be involved in the aetiopathogenesis of AD.

Adolescent↗
PubMed2002

The role of mast cells in the development of 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis in rats.

BACKGROUND: The role of mast cells in Crohn disease (CD) remains to be established. The aim of this study was to elucidate this in the development of CD-like colitis in rats by the use of mast-cell-deficient Ws/Ws and their control W+/W+ rats. METHODS: CD-like colitis was induced in both groups by an enema of 10 mg of 2,4, 6-trinitrobenzene sulfonic acid (TNBS) in 50% ethanol. Colonic damage, adhesion and colonic weight were measured at 7 and 14 days after the TNBS/ethanol enema. Rat mast cell protease-2 (RMCP-2) in the colonic tissue was also measured at 7 days after the enema. RESULTS: There was no significant difference between W+/W+ and Ws/Ws rats in terms of colonic damage, adhesion or colonic weight. The tissue content of RMCP-2 in Ws/Ws rats treated with either saline or TNBS/ethanol was only maintained at a much lower level than that in W+/W+ rats with the corresponding treatment. CONCLUSIONS: These results demonstrate that mast cells are not essential in the development of 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis in rats.

Animals↗
PubMed2001

Funnel chest: treatment strategy and follow-up.

Although funnel chest is the most frequently seen deformity of the anterior chest wall in children, there is still considerable controversy regarding three major aspects, namely, the frequency of such deformities, their physiological importance, and the methods available for treatment. We retrospectively analyzed our experience with the 154 patients managed in our department. In 81 of these an operation was performed (OP), and the clinical findings for this group were compared with the 73 patients in whom an operation was not performed (NOP). Evaluation included subjective findings, especially the views of the patients' parents, and objective findings, including chest radiographs, computed tomography (CT), spirogram, electrocardiography, and echocardiography. In all patients the assessment included postoperative respiratory symptoms, appearance of the chest, and psychological aspects related to the deformity. Post-operatively, respiratory symptoms almost invariably subsided. The cosmetic result could initially be regarded as satisfactory or fair during the first 10 years following surgery, but over time there was frequently increasing concern regarding the scar. The NOP patients showed significantly less severity of the funnel index compared with OP patients. However, there was no spontaneous improvement in the deformity in older patients; most of the NOP patients continued to show a cosmetic deformity and 26.7% had psychological problems. This retrospective study confirms that our treatment strategy of objective criteria for operation (functional compression index > 0.2, % vital capacity <80, and CT index less than 0.25) and timing of operation (between 4 and 6 years of age) provides good results. Based on the analysis of long-term follow-up, surgery is considered indicated in patients with severe deformity. However, in the interest of psychological development, the indications for surgery may be extended.

Abnormalities, Multiple↗
PubMed2001

Localization of human airway trypsin-like protease in the airway: an immunohistochemical study.

Human airway trypsin-like protease (HAT) has been isolated from mucoid sputum of patients with chronic airway diseases. In order to clarify the cellular source of this novel protease in the human airway, we examined the localization of immunoreactive HAT in bronchial tissues obtained at surgery and fixed in 4% paraformaldehyde using an extremely sensitive immunohistochemical technique called a catalyzed signal amplification method and a monoclonal antibody against recombinant HAT. HAT immunoreactivity was demonstrated in cytoplasm of ciliated cells of bronchial epithelium and/or at the basal part of cilia. No positive reaction was found in submucosal glands or mast cells. The heterogeneous distribution of HAT immunoreactivity within the bronchial epithelium indicates that its expression might be changeable and that it might be closely related to the physiological status of the airway epithelium. Non-specific but intense reaction caused by endogenous avidin-binding activity (EABA) was selectively detected in submucosal glands, but was effectively blocked by successive treatments with avidin and biotin. These results indicate that HAT may be synthesized in the ciliated cells and that it may play some physiological roles within the epithelial layer and on the airway surface. It is necessary to keep in mind that some cells show strong EABA, especially when a highly sensitive immunohistochemical technique is applied.

Antibodies, Monoclonal↗
PubMed2001

Two patients with severe alcoholic hepatitis accompanied by hypercytokinemia and granulocytic hyperelastasemia, successfully treated by intravenous infusion of urinastarine (Miraclid).

Severe alcoholic hepatitis (SAH) is not simply a disease of the liver, but it also causes infection and multiple organ failure, and therefore carries an extremely poor prognosis. We report the successful treatment of two patients with SAH. Case 1: The patient was a 55-year-old man. He was a heavy drinker whose alcohol intake had increased for some 3 years to 1.8 L sake a day. Slight clouding of consciousness, fever, and jaundice were evident on his admission to our hospital. Laboratory data showed leukocytosis with a predominance of polymorphonuclear leukocytes, and a decline in coagulability. He tested negative for various hepatitis virus markers. With the diagnosis of SAH made, steroid pulse therapy and bilirubin adsorption therapy were administered. The jaundice improved and the interleukin-8 (IL-8) level decreased. Continuous intravenous infusion of urinastarine (Miraclid) normalized the granulocyte elastase level. Improvement was also seen in coagulability, ascites, icterus and consciousness. Case 2: The patient was a 49-year-old man. He was a heavy drinker whose alcohol intake had increased for 1 month. Fever, jaundice, ascites, and mild disturbance of consciousness were evident at the time of admission. Examination on admission diagnosed SAH. Bilirubin adsorption and continuous intravenous infusion of urinastarine were initiated. As a result, circulating IL-8 level was decreased and coagulability was improved. Therapy for granulocytic hyperelastasemia and hypercytokinemia supervening on SAH is a new effective approach on improvement in the disease.

Blood Coagulation↗