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Biomedical subjects

K Yano

Publications and source records attributed to K Yano.

At least 19 recordsLinked to original sources

Significance of additional high-dose cytarabine in combination with cyclophosphamide plus total body irradiation regimen for allogeneic stem cell transplantation.

The combination of cyclophosphamide (CY) and total body irradiation (TBI) has been used as a standard conditioning regimen for allogeneic transplantation. Several studies showed an advantage of adding high-dose cytarabine (HDCA) to this regimen. To clarify the significance of additional HDCA, we conducted a retrospective multicenter study and compared the clinical results of these two regimens. From June 1985 to March 2003, 219 patients with hematological malignancies underwent allogeneic transplantation after conditioning with CY+TBI 12Gy (n=73) or CA+CY+TBI 12Gy (n=146). Engraftment, overall survival, transplant-related mortality (TRM), relapse rate and incidence of graft-versus-host disease (GVHD) were compared according to risks and donors. Addition of HDCA had no impact on the relapse rate in all subgroups, and it was associated with lower TRM among standard-risk patients after related transplantation, and with higher TRM and worse survival among standard-risk patients after unrelated transplantation. The incidence of acute GVHD was not significantly different between the two regimens, and HDCA resulted in a higher incidence of chronic GVHD among standard-risk patients after related transplantation. In summary, addition of HDCA is not beneficial for high-risk patients, and is not recommended for standard-risk patients receiving unrelated transplantation.

Adolescent↗

Risk and prognostic factors for Japanese patients with chronic graft-versus-host disease after bone marrow transplantation.

The incidence and prognostic factors for chronic graft-versus-host disease (cGVHD) were evaluated for 255 Japanese patients who survived more than 100 days after bone marrow transplantation, and of whom 119 (47%) developed cGVHD. Prior acute GVHD (grade 2-4) and use of an unrelated donor were significantly associated with the onset of cGVHD. Presence of cGVHD did not have an impact on mortality (hazard ratio (HR) = 0.89; 95% confidence interval (CI), 0.59-1.3). Three factors at diagnosis were associated with cGVHD-specific survival: presence of infection (HR = 4.1; 95% CI, 1.6-10.3), continuing use of corticosteroids at the onset of cGVHD (HR = 3.9; 95% CI, 1.7-9.1), and a Karnofsky performance score <80 (HR = 4.7; 95% CI, 2.0-11.3). The probability of cGVHD-specific survival at 4 years was 79% (95% CI, 70-86%). The severity and death rate of Japanese patients with cGVHD was lower than those for populations in Western countries, which might be the result of greater genetic homogeneity of Japanese ethnics. Our patients could not be accurately classified when the proposed prognostic models from Western countries were used, thus indicating the need for a different model to identify high-risk patients.

Adolescent↗

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Adult↗

Solid tumors after hematopoietic stem cell transplantation in Japan: incidence, risk factors and prognosis.

To evaluate the incidence, risk factors and prognosis for solid tumors after hematopoietic stem cell transplantation (HSCT) in Japan, 809 patients who had received HSCT between 1981 and 2000 were retrospectively analyzed. In all, 19 newly diagnosed secondary cancers were observed. The risk for cancer development was 2.8 times as high as that for expected cases. The cumulative incidence ratios at 5 and 10 years were 1.9 and 4.2%, respectively. The risk was significantly elevated for buccal cavity cancer (standard incidental ratio (SIR), 44.42: 95% confidence interval (CI) 17.86-91.51), esophageal cancer (SIR, 22.36: 95% CI 6.09-57.25), and cervical cancer (SIR, 8.58: 95% CI 1.04-31.01). Of 15 patients who developed solid cancers following allografting, 12 had chronic graft-versus-host disease (GVHD), and all 10 patients with squamous cell carcinoma of the buccal cavity or esophagus had chronic GVHD. On multivariate analysis, extensive chronic GVHD and age over 45 years at the time of transplantation were associated with a higher risk for solid cancers. In all, 17 patients received therapy for secondary cancers, nine of whom are still alive and the 5-year probability of survival from the diagnosis is 42.8%. Our data suggest that early detection of secondary cancers is very important in prolonging overall survival.

Adult↗

Ultraviolet B irradiation of human skin induces an angiogenic switch that is mediated by upregulation of vascular endothelial growth factor and by downregulation of thrombospondin-1.

BACKGROUND: We have previously demonstrated that skin-specific overexpression of the endogenous angiogenesis inhibitor thrombospondin (TSP)-1 prevented chronic ultraviolet (UV) B-induced angiogenesis, inflammatory cell infiltration and cutaneous photodamage in mice. OBJECTIVES: To elucidate the mechanisms by which acute UVB-induced angiogenesis induces dermal damage, and to study the molecular regulation of acute UVB-induced angiogenesis in human skin. METHODS: We subjected five healthy volunteers to acute UVB irradiation (2 minimal erythema doses) and performed histological analysis at 48 h after UVB irradiation. RESULTS: Histology revealed epidermal hyperplasia, infiltration of elastase-producing neutrophils and elastin fibre damage. Immunohistochemistry for CD31 demonstrated pronounced angiogenesis with a significant increase in both vascular density and vessel size, associated with increased endothelial cell proliferation. Whereas constitutive expression of TSP-1 but only weak expression of vascular endothelial growth factor (VEGF) were detected in normal human epidermis, pronounced downregulation of TSP-1 and upregulation of VEGF were observed in epidermal keratinocytes after acute UVB irradiation. These findings were confirmed by quantitative reverse transcription-polymerase chain reaction analysis after UVB irradiation of cultured HaCaT keratinocytes in vitro. CONCLUSIONS: Together, these data indicate that a disruption of the balance between VEGF and TSP-1 expression leads to a UVB-induced angiogenic switch, facilitating the infiltration of elastase-producing leucocytes and cutaneous photodamage.

Adult↗

Ultrasound evaluation of the fibrosis stage in chronic liver disease by the simultaneous use of low and high frequency probes.

A liver biopsy is currently considered the definitive diagnostic modality for establishing the severity of hepatic fibrosis. We analysed the diagnostic sensitivity and accuracy of ultrasound (US) using both low frequency and high frequency probes as a repeatable, inexpensive, and reliable method to determine the fibrosis stage in chronic liver disease and then compared our results with the histological findings. A total of 103 patients with chronic liver disease (60 males and 43 females, average age 51 years old) who had undergone both a liver biopsy and US with 2-5 MHz frequency and 5-12 MHz frequency probes were prospectively evaluated in this study. An US scoring system using both the low frequency and high frequency probes was performed by evaluating the edge, surface and parenchymal texture of the liver. Each score was obtained by evaluating three parameters; the bluntness of the liver edge, the irregularity of the surface and the coarseness of the parenchymal texture were evaluated and then compared with the histological findings. The US scores of the liver edge (rs: 0.6668), liver surface (rs: 0.9007) and liver parenchymal texture (rs: 0.8853) correlated significantly with the fibrosis stage obtained based on the biopsy findings. The accumulated US scores of these three parameters, however, was found to be the most reliable indicator (rs: 0.9524). Patients with an accumulated score of 6.5 or more were all found to have fibrosis stage 4 in which the accuracy of our scoring system for correctly predicting cirrhosis was found to be 100% sensitive. When an accumulated US score of 3 was interpreted to indicate mild fibrosis (a fibrosis score of 0 or 1), all 42 patients with stage 0 or 1 fibrosis were found to have an accumulated US score of 3 or less (a probability of 100%) and 42 of 53 patients with a score of 3 or less were found to have stage 0 or 1 fibrosis (specificity of 79.2%). An ultrasound evaluation of the liver fibrosis stage based on the scoring system using both low and high frequency probes was found to be a reliable and effective alternative to the histological staging in chronic liver diseases.

Biopsy↗

Characterization of functional effects of Z-338, a novel gastroprokinetic agent, on the muscarinic M1, M2, and M3 receptors expressed in Xenopus oocytes.

This study characterized the functional effects of a novel gastroprokinetic agent, N-[2-(diisopropylamino)ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]-1, 3-thiazole-4-carboxyamide monohydrochloride trihydrate (Z338), on the muscarinic M1, M2, and M3 receptors expressed in Xenopus oocytes using the two-electrode voltage clamp method. Z-338 did not produce by itself any currents in oocytes expressing muscarinic M1, M3 receptors or muscarinic M2 receptors/G protein-gated inward rectifying K+ channels (Kir3.1 channels). In oocytes expressing muscarinic M1 receptors, Z-338 inhibited the acetylcholine-induced Ca2+ -activated Cl- current with an IC50 of 1.8 microM. In oocytes expressing muscarinic M2 receptors/Kir3.1 channels, Z-338 inhibited the acetylcholine-induced K+ currents with an IC50 of 10.1 microM, whereas in oocytes expressing muscarinic M3 receptors, Z-338 did not inhibit the acetylcholine-induced Ca2+ -activated Cl- current in a concentration-dependent manner. These results indicate that Z-338 is a potent antagonist not for muscarinic M3 receptor but for both muscarinic M1 and M2 receptors. Thus, Z-338 is a gastrokinetic agent with a unique profile.

Acetylcholine↗

Metal ion absorption of carboxymethylcellulose gel formed by gamma-ray irradiation. For the environmental purification.

Carboxymethylcellulose (CMC) is well known as a safe and biodegradable material, which is widely used as food additives, wash paste, etc., in our daily life. Aiming at the environmental purification of this eco-friendly substance, the authors have investigated Cu2+ absorption property of CMC gel that was crosslinked by irradiating with gamma-rays without toxic crosslinker. The CMC gel has revealed to capture Cu2+ of which number depends on the gamma-ray dose as well as the CMC concentration, indicating the chelation by carboxyl group at the end of the side chain.

Carboxymethylcellulose Sodium↗

Elucidation of adsorption mechanism of bone-staining agent alizarin red S on hydroxyapatite by FT-IR microspectroscopy.

To elucidate adsorption mechanism of alizarin red S (ARS), which is often used for staining bones in histology, adsorption of ARS on hydroxyapatite, Ca10(PO4)6(OH)2 (HAP), was investigated by a batch method, compared with alizarin, phenols, and benzenesulfonates. We found that ionized 1-, 2-OH groups (1-, 2-O(-)) of ARS can be electrostatically bound to Ca2+ on HAP, but that the 3-SO3(-) group of ARS hardly participates in adsorption on HAP. ARS-adsorbed HAP (ARS-HAP) in dark reddish violet was also prepared and analyzed by FT-IR microspectroscopy to gain structural information on bonding between ARS and HAP. The obtained spectrum, which was converted to difference spectra, indicated a single band of nu(C=O) at 1627 cm(-1) and two types of symmetric C=O stretching bands of nu(s)(C=O) + nu(C=C) at 1345 cm(-1) and nu(s)(C=O) + delta(O-C=C) at 1272 cm(-1). These bands imply the existence of a salt form in ARS-HAP via 1-, 2-OH groups of ARS. As a result of the existence of a chelate form in ARS-HAP via 1-OH and 9-C=O groups of ARS, two bands of nu(C=C) + nu(C=O) at 1572 cm(-1) and nu(C=O) + nu(C=C) at 1537 cm(-1) were also observed. In addition, ARS was almost desorbed from colored ARS-HAP at 50 degrees C by using neutral phosphate buffer to recover slightly pale pinkish HAP, or De-ARS-HAP. The desorbed ARS belongs to ARS previously adsorbed on HAP by salt formation, while the remaining color on De-ARS-HAP indicates ARS still adsorbed on HAP by chelate formation. Consequently, we elucidated two adsorption mechanisms of ARS on HAP: The major adsorption is salt formation made up with 1-, 2-O(-) of ARS and Ca2+ on HAP, and the minor adsorption is chelate formation made up with 1-O(-) and 9-C=O of ARS and Ca2+ on HAP.

Adsorption↗

Cytomegalovirus antigenemia and outcome of patients treated with pre-emptive ganciclovir: retrospective analysis of 241 consecutive patients undergoing allogeneic hematopoietic stem cell transplantation.

CMV disease remains a major infectious complication after allogeneic hematopoietic stem cell transplantation (HSCT). To investigate the relationship between CMV antigenemia, treatment with ganciclovir (GCV), and outcome, we retrospectively analyzed 241 consecutive patients at risk for CMV infection who underwent allogeneic HSCT. Antigenemia-guided pre-emptive strategy with GCV was used for all patients. CMV antigenemia developed in 169 patients (70.1%), and CMV disease in 18 patients (7.5%). Multivariate analysis showed that acute GVHD (grades II-IV) was the only risk factor for developing antigenemia, and acute GVHD and advanced age for CMV disease. GCV use, as well as acute GVHD and advanced age, significantly increased the risk for bacterial and fungal infection after engraftment. Those who developed CMV antigenemia had a poorer outcome than those who did not (log-rank, P=0.0269), although the development of CMV disease worsened the outcome with only borderline significance (log-rank, P=0.0526). In conclusion, detection of antigenemia proved to be a poor prognostic factor for HSCT patients, which may be attributed to a combination of factors, including CMV disease itself, the effect of treatment, and a host status that allows for reactivation of CMV. Optimal pre-emptive strategy needs to be determined.

Adolescent↗

Sisters with atypical Fabry's disease with complete atrioventricular block.

A 56 year old woman with severe right heart failure and complete atrioventricular block was referred to hospital for further examination. Symptoms and signs suggestive of Fabry's disease, such as corneal opacities, acroparaesthesias, hypohidrosis, and angiokeratoma, were not noted. Echocardiography showed a diffuse hypertrophic left ventricular wall and paradoxical movement of the interventricular septum. Cardiac catheterisation showed restrictive-type ventricular dysfunction. Left ventricular endomyocardial biopsy showed central vacuolar degeneration of myocytes with inclusion bodies, which had a concentric lamellar configuration under electron microscopy. This finding is specific for Fabry's disease. The patient's elder sister had experienced an almost identical clinical course and histological findings of myocardial cells on necropsy. In conclusion, two sisters were encountered displaying interesting cases of atypical Fabry's disease. Symptoms began with complete atrioventricular block and histological myocardial findings were specific for Fabry's disease.

Biopsy↗

Changes in osteoprotegerin and markers of bone metabolism during glucocorticoid treatment in patients with chronic glomerulonephritis.

It is well known that long-term glucocorticoid treatment causes osteoporosis, but the precise mechanism remains unclear. Recently, osteoprotegerin (OPG) has been identified as a cytokine that inhibits osteoclast differentiation. We have previously demonstrated that serum OPG is suppressed by glucocorticoids. Therefore, the present study was carried out to clarify the interrelationships between OPG and other markers of bone metabolism during glucocorticoid treatment. Thirteen patients (7 men, 6 women; 44.1 +/- 5.9 years old) with chronic glomerulonephritis who were to be treated with glucocorticoids for the first time were chosen for this study. Markers of bone metabolism, including serum OPG, osteocalcin (OC), bone-specific alkaline phosphatase activity (bAP), parathyroid hormone (PTH), tartrate-resistant acid phosphatase (TRAP), and bone mineral density (BMD), were measured before and during the treatment period. Glucocorticoids significantly reduced BMD of the lumbar spine in the 6 month treatment period (p < 0.01). Serum OPG was decreased significantly by glucocorticoids within 2 weeks (p < 0.001), and serum TRAP, a marker of bone resorption, was markedly increased (p < 0.001). On the other hand, there were no remarkable changes in serum PTH. Serum OC and bAP, markers of bone formation, were transiently reduced during the treatment period (p < 0.01). Furthermore, only serum OPG was positively and independently correlated with percentage BMD of age-matched reference (%AMR). These findings imply that glucocorticoid-induced bone loss develops rapidly via enhanced bone resorption and suppressed bone formation. Moreover, the increased bone resorption caused by glucocorticoids may be, at least in part, mediated by inhibition of OPG, not increment of PTH.

Adult↗

The effects of body mass index on age at menopause.

OBJECTIVE: We examined which of body mass index (BMI, kg/m(2)), serum cholesterol (mg/dl), or systolic blood pressure (SBP, mm Hg) affected age at natural menopause. DESIGN: A population-based follow-up program. METHODS: We determined the age at natural menopause in 1136 women followed biennially since their first examination in 1958-1959 through the 16th examination in 1988-1989. Four-hundred and ninety-three naturally menopausal women were classified into three groups by BMI, serum cholesterol and SBP measurement levels at age 40 or 41 y: the upper 25%, middle 50%, and lower 25%. We then studied whether there was a difference in age at menopause among the three groups thus classified. The 1136 natural menopausal women were also classified as early (n=454; 45-49 y at menopause (48.3+/-1.2 y)) or late (n=682; >or=50 y at menopause (52.3+/-1.6 y)) menopausal and compared for premenopausal trends in BMI, serum cholesterol and SBP in the early and late menopausal women by means of a longitudinal data analysis model. RESULTS: When women were classified into the three groups based on a BMI that was measured at 40 or 41 y, age at menopause in the upper 25% (50.4+/-2.8 y) was significantly higher (P<0.05) than that in the lower 25% (49.7+/-2.8 y). The entire premenopausal trend in BMI in late menopausal women shifted upward compared to that in early menopausal women. On the other hand, the premenopausal trend more than 4 y before menopause in serum cholesterol and the entire premenopausal trend in SBP in late menopausal women were identical to those in early menopausal women. CONCLUSION: Among the variables studied, only BMI is related to age at menopause, and the greater the BMI, the later the age at menopause.

Adult↗

Giant basal cell carcinoma affecting the lower abdominal, genital and bilateral inguinal regions.

We describe a giant basal cell carcinoma, measuring 40 cm x 20 cm, of the lower abdominal, genital and bilateral inguinal regions. The rectus abdominis muscle and the adductor magnus muscle were exposed centrally, and the penis and scrotum were completely destroyed. Reconstruction was performed with a fillet thigh flap, and an excellent result was obtained 1 year after surgery.

Abdominal Wall↗

[Synchronous tumors consisted of bronchial carcinoid and adenocarcinoma of the lung].

We report a case of synchronous tumors consisted of bronchial carcinoid and adenocarcinoma of the lung. A 58-year-old female was referred to our hospital after screening, because an abnormal shadow was noted in the right lung on her computed tomography (CT) of the chest. CT scans showed a peripheral pulmonary mass in the right middle lobe and a nodule around the right lower lobe bronchus. The nodular lesion like swollen lymph node was diagnosed as bronchial carcinoid originated in B6 by bronchoscopy. The pulmonary mass was diagnosed as adenocarcinoma by using core needle biopsy during operation. Right middle and lower bilobectomy and mediastinal lymph node dissection were performed. Coincidence of a bronchial carcinoid and an adenocarcinoma of the same side of the lung is a rare occurrence.

Adenocarcinoma↗

Immunological study on circulating murine osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF): possible role of OPG/OCIF in the prevention of osteoporosis in pregnancy.

Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a soluble member of the tumor necrosis factor receptor family and plays a crucial role in the negative regulation of osteoclastic bone resorption. We have immunized OPG/OCIF knockout mice with murine rOPG/rOCIF and established a panel of hybridomas producing monoclonal antibodies (mAbs) to murine rOPG/rOCIF. Utilizing the mAbs, we developed enzyme-linked immunosorbent assay (ELISA) systems: one detecting both homodimeric and monomeric forms of murine OPG/OCIF and the other detecting only dimeric form of murine OPG/OCIF. With the aid of these ELISA systems we showed that OPG/OCIF is present mainly as a monomer in murine blood. The concentration of OPG/OCIF in normal mouse sera was approximately 500 pg/ml and there was no statistical difference in the serum concentration of OPG/OCIF among genders, age, and strains. Interestingly, the concentration of circulating OPG/OCIF in mouse markedly increased during pregnancy. The result indicated that circulating OPG/OCIF plays an important role in the protection of bone from excess resorption during pregnancy in mammals.

Animals↗