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Biomedical subjects

Y Ohashi

Publications and source records attributed to Y Ohashi.

At least 271 records · Page 15Linked to original sources
PubMed1997

Serum leptin levels are associated with hyperinsulinemia independent of body mass index but not with visceral obesity.

To examine the relationship between leptin levels and visceral obesity or plasma insulin levels, we studied serum leptin levels, fat distribution assessed by CT scan, and plasma insulin levels during 75 g oral glucose load in 100 Japanese men. Regression analysis adjusted by age and body mass index (BMI) showed leptin levels to be associated with visceral fat area(V)(p = 0.003), subcutaneous fat area(S)(p < 0.0001), and V + S(p < 0.0001), but not with V/S ratio(p = 0.897). By regression analysis adjusted by age, BMI, and V + S, serum leptin levels were still highly and positively correlated with plasma insulin levels during 75 g oral glucose load (p < 0.001), insulin resistance index(p < 0.001), and beta cell function index(p = 0.009) in homeostasis model assessment. These data suggest that hyperinsulinemia, but not visceral obesity, may be regulators of serum leptin levels independent of BMI.

Adult↗
PubMed1997

Mixed models for bivariate response repeated measures data using Gibbs sampling.

Repeated measures data are frequently incomplete, unbalanced and correlated. There has been a great deal of recent interest in mixed effects models for analysing such data. In this paper, we develop bivariate response mixed effects models that are a generalization of linear mixed effects models for a single response variable. We describe their estimation procedures using a Markov chain Monte Carlo method, the Gibbs sampler. We illustrate the methods with analyses of intravenous vitamin D3 administration for secondary hyperparathyroidism in hemodialysis patients. In these data there were two response variables on each individual (PTH and calcium level). This study also suffered from attrition, like many longitudinal studies. While, considering the study design, it was reasonable to assume the drop-out mechanism for the calcium (Ca) level to be 'missing at random', the drop-out mechanism for the PTH level was likely to be non-ignorable. We found that the posterior treatment effects for the PTH level by the single response model were underestimated compared with those obtained by the bivariate response model, while there were little differences in the posterior features for the Ca level under both models.

Calcium↗
PubMed1997

Positron emission tomographic imaging of head and neck lesions.

Positron emission tomography (PET) produces images that reflect the rate and distribution of biochemical and physiological processes in tissue in vivo. This has been observed with many types of neoplasm not evident when using such anatomical imaging techniques as computed tomography or magnetic resonance imaging. We evaluated the feasibility of 2-18F-2-deoxy-D-glucose (FDG) PET studies in diagnosing and assessing the effects of treatment on lesions of the tongue, maxillary sinus and nasopharynx. FDG-PET imaging was performed 45 times in 17 patients with tumors before treatment. Ten patients with malignant lesions also underwent imaging after treatment. The differential absorption ratio (DAR) of the isotope was calculated at 55 min and the time activity curve (TAC) was obtained by dynamic emission scans for 0-55 min following injection of FDG. FDG-PET images, DAR and TAC were evaluated in all lesions. Findings showed that FDG-PET images could be used to diagnose malignant tumors and evaluate treatment when the DAR was > 4.0 and TAC was steep upward. Images suggestive of benign lesions had low DAR values (< 4.0) and mildly upward or flat TACs.

Absorption↗
PubMed1997

Flow characteristics and required control algorithm of an implantable centrifugal left ventricular assist device.

As the clinical application of LVADs has increased, attempts have been made to develop smaller, less expensive, more durable and efficient implantable devices using rotary blood pumps. Since chronic circulatory support with implantable continuous-flow LVADs will be established in the near future, we need to determine the flow characteristics through an implantable continuous-flow LVAD. This study describes the flow characteristics through an implantable centrifugal blood pump as a left ventricular assist device (LVAD) to obtain a simple non-invasive algorithm to control its assist flow rate adequately. A prototype of the completely seal-less and pivot bearing-supported centrifugal blood pump was implanted into two calves, bypassing from the left ventricle to the descending aorta. Device motor speed, voltage, current, flow rate, and aortic blood pressure were monitored continuously. The flow patterns revealed forward flow in ventricular systole and backward flow in diastole. As the pump speed increased, an end-diastolic notch became evident in the flow profile. Although the flow rate (Q [l/min]) and rotational speed (R [rpm]) had a linear correlation (Q = 0.0042R - 5.159; r = 0.96), this linearity was altered after the end-diastolic notch was evident. The end-diastolic notch is considered to be a sign of the sucking phenomenon of the centrifugal pump. Also, although the consumed current (I [A]) and flow rate had a linear correlation (I = 0.212Q + 0.29; r = 0.97), this linearity also changed after the end-diastolic notch was evident. Based upon the above findings, we propose a simple algorithm to maintain submaximal flow without inducing sucking. To maintain the submaximal flow rate without measuring flow rate, the sucking point is determined by monitoring consumed current according to gradual increases in voltage.

Algorithms↗
PubMed1997

A mutation of the beta 3-adrenergic receptor is associated with visceral obesity but decreased serum triglyceride.

The Trp64Arg mutation of the beta 3-adrenergic receptor (beta 3AR) is prevalent in several ethnic groups and is associated with weight gain, and some features of syndrome X such as insulin resistance and dyslipidaemia. Nevertheless, it is not known at present whether this mutation is associated with visceral obesity, which is an important risk factor for the development of hypertension, dyslipidaemia, insulin resistance, non-insulin-dependent diabetes mellitus, and atherosclerosis. To investigate whether this mutation may contribute to visceral obesity, we studied the relationships between beta 3AR genotypes and clinical phenotypes. The Trp64Arg allele of beta 3AR was examined in 278 Japanese men with respect to variables relating to visceral obesity assessed by computerised tomography. To detect the Trp64Arg mutation, polymerase chain reaction-restriction fragment length polymorphism analysis using Bst NI digestion was performed. This mutation was more frequently observed in subjects with higher body mass index (BMI) (p = 0.02). Moreover, in 120 subjects with a moderate degree of obesity (22 < or = BMI < 26.4 kg/m2), the mutation (homozygotes and heterozygotes) was associated with visceral obesity (higher ratio of visceral to subcutaneous fat area; V/S) (p = 0.03). Furthermore, the Trp64Arg allele was more frequent in subjects with lower serum triglyceride levels (p = 0.02) and the Trp64Arg homozygotes, but not heterozygotes, exhibited lower triglyceride levels. Thus, this mutation appears to be associated with visceral obesity but with lower serum triglyceride. It is suggested that those with the mutation may describe a subset of subjects characterized by decreased lipolysis in visceral adipose tissue.

Adult↗
PubMed1997

Platelet activating factor compromises airway epithelial defense functions.

BACKGROUND: The mechanism of disruption of the epithelial defense function observed in asthmatic airways is considered to be largely the result of mediators involved in allergic responses. Platelet activating factor (PAF) might be a key mediator involved in this mechanism. OBJECTIVE: This study was designed to determine whether PAF is capable of compromising the epithelial defense functions, such as tight junctional barriers and the mucociliary system. METHODS: A total of 120 healthy rabbits were used. Twenty of them were used as normal controls. Eighty rabbits were treated with inhalation of 10 ml of PAF (200 microg/ml), and 20 animals were used for the examination of epithelial defense functions of the trachea at 1, 10, 20, and 30 days after inhalation of PAF. Epithelial defense functions of the trachea were evaluated by ciliary activity, mucociliary transport velocity, epithelial permeability to fluorescein isothiocyanate dextrans (70,000 d), and electron microscopy of the epithelial structure. RESULTS: PAF inhalation induced a significant decrease in ciliary activity and mucociliary transport velocity, which persisted for up to 20 days. PAF inhalation also caused a significant 7.4-fold increase in epithelial permeability to fluorescein isothiocyanate dextrans at I and 10 days. This increased epithelial permeability returned to the normal level 20 days after PAF inhalation. However, electron microscopy demonstrated no apparent evidence of epithelial shedding. CONCLUSIONS: PAF-induced prolonged dysfunction of both the epithelial junctional barrier and the mucociliary system may allow enhanced entry of allergen molecules, as well as bronchoactive agonists to the airway parenchyma and may also significantly contribute to an increased airway responsiveness.

Administration, Inhalation↗
PubMed1997

Serum levels of specific IgE, soluble interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in seasonal allergic rhinitis.

BACKGROUND: There is increasing evidence that soluble interleukin-2 receptor (sIL-2R) might reflect T cell activation in vivo and soluble intercellular adhesion molecule-1 (sICAM-1) might reflect the ongoing inflammatory response in the inflamed site. OBJECTIVE: The aim of this study was to determine the effect of antihistamine tablets and allergen-specific immunotherapy on the seasonal changes in specific IgE, sIL-2R, and sICAM-1 in the serum of patients with seasonal allergic rhinitis. METHODS: This prospective study included 99 patients with seasonal allergic rhinitis due to Japanese cedar pollens and 27 nonatopic healthy volunteers. The patients were divided into an antihistamine-treated group and an immunotherapy group. Serum samples were collected before and during the pollen season from each patient to determine specific IgE, sIL-2R, and sICAM-1. RESULTS: Levels of sIL-2R before the pollen season did not differ significantly among the nonatopic group, the antihistamine-treated group, and the immunotherapy group. The levels of sICAM-1 before the pollen season were significantly higher in the antihistamine-treated group and in the immunotherapy group than in the nonatopic group. Seasonal increase in specific IgE was significant in the antihistamine-treated group regardless of their clinical outcomes. In contrast, significant increase in specific IgE was observed during the pollen season in poor responders but not in good responders to immunotherapy. Serum levels of sIL-2R and sICAM-1 were significantly increased during the pollen season in poor responders of the antihistamine-treated group and the immunotherapy group. On the other hand, neither seasonal increase in sIL-2R nor sICAM-1 was significant in good responders of the antihistamine-treated group and the immunotherapy group. CONCLUSIONS: Serum levels of sICAM-1 are higher in patients with seasonal allergic rhinitis, even outside of the pollen season when the allergen does not naturally exist. Seasonal changes in serum sICAM-1 as well as sIL-2R and specific IgE are probably objective markers to indicate the clinical efficacy of antihistamines and immunotherapy on seasonal allergic rhinitis.

Adult↗
PubMed1997

Successful treatment of steroid-resistant severe acute GVHD with 24-h continuous infusion of FK506.

We report our findings in two cases of steroid-resistant severe acute GVHD after allogeneic BMT successfully treated with FK506 (tacrolimus). An 18-year-old female (patient 1) who underwent BMT from an HLA-identical sibling for ALL in first CR, developed generalized erythema and profuse watery diarrhea, which progressed to acute GVHD of grade III severity, resistant to steroid control. After continuous 24-h administration of FK506, the diarrhea improved within 10 days. Patient 2, a 9-year-old girl with AML who underwent unrelated BMT, had skin, gut and liver lesions of acute GVHD grade IV, which did not respond to high-dose steroid therapy. They were controlled, however, by continuous intravenous infusion of FK506. Both patients are still surviving after more than 1 year without any acute GVHD sequelae or signs of chronic illness. The adverse effects of FK506 were mild and tolerable in both cases. Comparison of our findings with those in the literature suggests that it is important to give FK506 at plasma concentrations as high as 25-35 ng/ml by continuous intravenous infusion for extended periods to control steroid-resistant severe acute GVHD.

Acute Disease↗
PubMed1997

The effect of immunotherapy on the serum levels of eosinophil cationic protein in seasonal allergic rhinitis.

The role of serum eosinophil cationic protein levels in allergic rhinitis is controversial. It is also unclear whether with immunotherapy it is possible to reduce these serum levels in allergic diseases. We studied serum eosinophil cationic protein levels in patients with cedar-induced allergic rhinitis and compared them with non-atopic controls. The second aim of this study was to elucidate whether immunotherapy is capable of decreasing the seasonal elevation in serum eosinophil cationic protein levels in seasonal allergic rhinitis. The serum eosinophil cationic protein levels of the untreated patient group were significantly higher than those of the non-atopic controls. The levels in patients who received immunotherapy for 2 yr were also significantly higher than those of the non-atopic controls. However, the levels were not different between the patients undergoing immunotherapy for over 3 yr and the non-atopic controls. The serum levels of the 31 patients treated with immunotherapy correlated with the duration of immunotherapy. In conclusion, the serum eosinophil cationic protein levels are higher in untreated patients with seasonal allergic rhinitis and this seasonal activation in circulating eosiohophils decreases gradually during immunotherapy, but this inhibitory effect becomes apparent only after a number of years of immunotherapy. This prevention of seasonal eosinophil activation is one of the mechanisms responsible for the clinical effect of immunotherapy.

Adolescent↗
PubMed1997

Serum level of soluble interleukin-2 receptor in patients with seasonal allergic rhinitis.

The rate of release of the soluble form of interleukin-2 receptor (soluble IL-2R) reflects T cell activation in vivo. Since T lymphocytes play a central role in respiratory allergic disorders, the measurement of serum levels of soluble IL-2R may be useful in analysing the disease state of allergic disorders. The study has aimed at investigating the seasonal changes in serum soluble IL-2R in 81 patients with seasonal allergic rhinitis due to Japanese cedar pollens, with special reference to the effect of anti-allergic pharmacotherapy and immunotherapy. Serum samples were obtained twice from each patient, before and during the pollen season, and all the serum samples were simultaneously used for determination of soluble IL-2R and cedar pollen-specific immunoglobin E (IgE). Seasonal elevation in soluble IL-2R was not associated with the good clinical outcome but was associated with the poor clinical outcome, irrespective of pharmacotherapy or immunotherapy. Additionally, successful immunotherapy suppressed seasonal elevation of serum soluble IL-2R more strongly than successful pharmacotherapy, and seasonal increase rates in soluble IL-2R were inversely correlated with the duration of immunotherapy. Seasonal increase rates in soluble IL-2R were significantly correlated with seasonal increase rates in specific IgE in both the medication group and the immunotherapy patients. These results may suggest that seasonal changes in serum soluble IL-2R may serve as an indicator for clinical outcome of seasonal allergic rhinitis, that the magnitude of T cell activation could affect specific IgE production, and that T cell activation could be gradually modulated as immunotherapy proceeds. In conclusion, seasonal changes in serum soluble IL-2R may serve as an objective indicator for clinical outcome of seasonal allergic rhinitis.

Adolescent↗
PubMed1997

Immunotherapy affects the seasonal increase in specific IgE and interleukin-4 in serum of patients with seasonal allergic rhinitis.

This study was designed to determine seasonal changes in cytokines, soluble CD23 and specific IgE in the serum of patients with seasonal allergic rhinitis, and the effect of immunotherapy on these seasonal changes. Fifty-four patients with seasonal allergic rhinitis caused by Japanese ceder pollens were divided into a medication group and an immunotherapy group. The patients of the medication group were treated with non-sedating antihistamines alone during the pollen season. The patients of the immunotherapy group had been treated for variable periods (mean, 5.0 +/- 3.2 years) with immunotherapy using japanese cedar pollen antigens. Serum samples were collected before and during the pollen season from each patient, to determine specific IgE, interleukin-4 (IL-4), interferon-gamma (IFN-gamma) and soluble CD23 levels in serum. A significant increase in specific IgE and IL-4 and a significant decrease in IFN-gamma were observed during the pollen season in the medication group. In contrast, in the immunotherapy group, none of specific IgE, IL-4 and IFN-gamma was significantly changed following natural exposure to pollens. However, these effects were not significant in patients undergoing immunotherapy for 3 or fewer years. Seasonal rates of increase in specific IgE and IL-4 differed significantly between good responders and poor responders to immunotherapy, but seasonal rates of decrease in IFN-gamma did not. A seasonal rate of increase in soluble CD23 was significantly correlated with a seasonal rate of increase in specific IgE, in both the medication and the immunotherapy groups. The seasonal rate of increase in soluble CD23 was significantly smaller in the good responders than in the poor responders to immunotherapy. In conclusion, pollen immunotherapy reduces the seasonal increase in specific IgE, IL-4 and soluble CD23 in serum, and in addition switches the seasonal preferential activation of Th-2 cells to reciprocal activation of Th-1 cells with treatment over several years. It is likely that the mechanisms responsible for the clinically beneficial effects of immunotherapy principally involve the modulation of Th-2 rather than Th-1 cytokines.

Adult↗
PubMed1997

Phase I study of cladribine (2-chlorodeoxyadenosine) in lymphoid malignancies. Cladribine Study Group.

Cladribine (2-chlorodeoxyadenosine;) is a purine analogue with clinical activity against hairy cell leukemia, chronic lymphocytic leukemia and indolent lymphoma. To clarify the toxicity profiles of cladribine, we conducted a phase I and pharmacological study of cladribine with a schedule of seven-day continuous intravenous infusion every 28 days up to a maximum of three cycles. We enrolled 10 previously-treated patients with various lymphoid malignancies. No dose-limiting toxicity (grade 4 hematologic and/or grade 3 or more non-hematologic) was observed in the three patients who received 0.06 mg/kg/day (Level 1). Of the seven patients who received 0.09 mg/kg/day (Level 2), one patient developed grade 4 hypoxemia and grade 4 thrombocytopenia, and another developed grade 4 neutropenia. Of the seven patients treated at Level 2, one with cutaneous T-cell lymphoma attained complete remission, and one with mantle cell lymphoma, one with chronic lymphocytic leukemia and one with adult T-cell leukemia-lymphoma attained partial remission. A pharmacokinetic analysis of the seven patients without leukemic cells showed that their area under the concentration versus time curves of plasma cladribine increased dose-dependently from 2661.3 +/- 300.4 nM x h at Level 1 (n = 3) to 3411.3 +/- 341.0 nM x h at Level 2 (n = 4) (P = 0.034). We conclude that the recommended phase II dose of cladribine (0.09 mg/kg/day as a seven-day continuous i.v. infusion) in Caucasian patients can be safely administered to Japanese patients. The encouraging results prompted us to plan subsequent phase II studies of cladribine against adult T-cell leukemia-lymphoma, hairy cell leukemia and indolent lymphoma.

Aged↗
PubMed1997

A re-analysis of a randomized clinical trial for gastric cancer using interval censoring.

In a previous randomized clinical trial against curatively resected gastric cancer, we compared the effect of immunochemotherapy to chemotherapy and obtained significantly better survival and disease-free survival time (DFS) in a combined therapy group. Although DFS was analysed with a conventional approach in which the onset of relapse was defined as the diagnosis of relapse, we considered it necessary to re-analyse the data and compare the results of an interval-censored approach with the conventional approach, in order to examine whether the conclusion might be altered depending on the approach.

Disease-Free Survival↗
PubMed1997

Natural course of serum-specific immunoglobulin E and immunoglobulin G4 for a span of eight years in untreated patients with perennial allergic rhinitis.

During the past two decades, considerable attention has been devoted to the clinical role of serum-specific IgE and IgG4 following immunotherapy. To definitely discuss the clinical role of serum-specific IgG4, we should know the natural course of serum-specific IgG4 in the untreated patient with allergic rhinitis. To our knowledge, however, no such kind of study can be found in the literature. Our present study focused on the long-term follow-up of serum-specific IgE and IgG4 in patients who were not treated with immunotherapy for perennial allergic rhinitis. They were scheduled to take no medication for their perennial nasal symptoms for 8 years. Serum-specific IgE and IgG4 in untreated patients with perennial allergic rhinitis never significantly change during the observation period. These data will be of great value for studies in serologic changes following active treatment for atopic diseases. Additionally, our study suggests that a reduction in serum-specific IgE and an increase in serum-specific IgG4 following immunotherapy are not the result of an immunotherapy-independent and age-related phenomenon but the result of active immunologic modulation by immunotherapy.

Adjuvants, Immunologic↗
PubMed1997

Soluble intercellular adhesion molecule-1 level in sera is elevated in perennial allergic rhinitis.

Soluble intercellular adhesion molecule-1 (sICAM-1) in sera was measured in some allergic disorders, but serum sICAM-1 levels in perennial allergic rhinitis remain to be determined. Our study was aimed at elucidating whether the serum sICAM-1 levels in patients with perennial allergic rhinitis are different from those in nonatopic healthy volunteers and whether immunotherapy can modulate sICAM-1 levels. Serum sICAM-1 was determined in 20 nonallergic volunteers and 137 patients with perennial allergic rhinitis by a sandwich enzyme-linked immunosorbent assay. Our study demonstrated that the level of sICAM-1 in untreated patients is significantly elevated, as compared with nonatopic subjects. Immunotherapy could decrease sICAM-1 in perennial allergic rhinitis, but this suppressive effect became apparent only after many years of immunotherapy. In patients on immunotherapy, a close correlation was observed between sICAM-1 and nasal symptom scores. To take these lines of evidence together, a decrease in sICAM-1 might be related to the working mechanism of immunotherapy, and serum sICAM-1 could be used to monitor the effect of immunotherapy.

Adult↗
PubMed1997

Effect of immunotherapy on seasonal changes in serum-specific IgE and IgG4 in patients with pollen allergic rhinitis.

Serum specific IgE and IgG4 in 70 patients with seasonal rhinitis caused by Japanese cedar pollens were determined before and during the pollen season. Seasonal increase rate in specific IgE was significantly smaller in the immunotherapy patients than the pharmacotherapy patients, and seasonal increase in specific IgG4 was significant in the immunotherapy patients only. Seasonal increase rate in specific IgE was not significantly different between the patients who responded markedly to short-term immunotherapy and those who did not. On the other hand, seasonal increase rate in specific IgG4 was significantly different between them. In contrast, seasonal increase rate in specific IgE was significantly smaller in the patients who showed marked response to the long-term immunotherapy than those who did not show marked response to the long-term immunotherapy, but seasonal increase rate in specific IgG4 was not significantly different between them. In conclusion, our results suggest that modulation of specific IgG4 response and specific IgE response might be involved in the early and late symptom relief during immunotherapy, respectively. However, further studies might be necessary to definitively establish the clinical roles of specific IgE and specific IgG4 in immunotherapy.

Adolescent↗
PubMed1997

Reopening of macular holes in highly myopic eyes with retinal detachments.

BACKGROUND: Gas tamponade with or without vitrectomy is commonly used to treat retinal detachment resulting from a macular hole in a highly myopic eye. Redetachment of the retina occurs frequently, however, and the pathogenesis of redetachment is unclear. One possible mechanism leading to redetachment is tangential traction caused by an epiretinal membrane of the posterior retina. METHODS: Eleven consecutive highly myopic eyes with retinal detachment resulting from a macular hole were treated by vitrectomy, gas or silicone oil tamponade, and removal of an epiretinal membrane. Surgical outcomes and clinical characteristics of these patients were reviewed. RESULTS: An epiretinal membrane was found to be present in all eyes. Of 11 eyes, removal of an epiretinal membrane was complete in six eyes, and macular holes remained closed in all 6 eyes. In five of the 11 eyes, removal of the epiretinal membrane was incomplete. In four of these five eyes, the macular hole reopened. CONCLUSION: Reopening of the macular holes most likely were caused by tangential traction of the remaining epiretinal membranes. It seems that it is important to remove epiretinal membranes as completely as possible during vitrectomy for retinal detachment resulting from a macular hole in a highly myopic eye.

Aged↗