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Biomedical subjects

Y Ohno

Publications and source records attributed to Y Ohno.

At least 73 records · Page 4Linked to original sources

Dietary habits and risk of lung cancer death in a large-scale cohort study (JACC Study) in Japan by sex and smoking habit.

Lung cancer has increased and is the leading cause of cancer death among Japanese males. The associations of dietary habits with the risk of lung cancer death were evaluated by sex and smoking habits in this study. In the Japan Collaborative Cohort (JACC) Study, a cohort established in 1988 - 90 and consisting of 42 940 males and 55 308 females was observed for lung cancer deaths up to the end of 1997. During the observation period, 446 males and 126 females died of lung cancer. A self-administered food frequency questionnaire was used as the baseline survey. Hazard ratios for dietary factors were calculated by Cox's proportional hazards model. Among males, a high intake of ham and sausages, cheese, green-leafy vegetables, oranges, and other fruits significantly and dose-dependently decreased the risk of lung cancer death. Among females, a high intake of miso-soup, ham and sausages, and liver significantly and almost dose-dependently increased the risk. Vegetables and fruits rich in antioxidative and carcinogenic agents reduced the risk of lung cancer deaths among male smokers more than among female nonsmokers. The results among female nonsmokers were partially consistent with the hypothesis that high fat consumption increases the risk of lung cancer, especially that of adenocarcinoma.

Adult↗

Associations of alcohol drinking and nutrient intake with chronic pancreatitis: findings from a case-control study in Japan.

OBJECTIVE: The aim of this study was to examine the association of alcohol drinking and nutrient intake with chronic pancreatitis in a hospital-based case-control study. METHODS: From July, 1997, to December, 1998, 91 male patients, who were newly diagnosed as having chronic pancreatitis, were recruited as cases, and 175 controls were individually matched to each case for gender, age (+/-5 yr), hospital, and time of the first visit to a hospital (+/-1 yr). Information on demographic characteristics, smoking and drinking, and dietary habits were collected by a self-administered questionnaire. The strength of associations was examined by odds ratios (ORs) and 95% CIs calculated from conditional logistic regression models. RESULTS: Our study showed that the more the daily amount of alcohol drinking, the larger the OR. Men who consumed > or =100 g ethanol/day were at an approximately 11-fold increased risk as compared with nondrinkers. Long-term alcohol consumption (>35 yr) was associated with the increased risk (OR = 4.0). Risk of chronic pancreatitis remarkably increased with increasing cumulative alcohol consumption (trend p = 0.0001). Intakes of saturated fatty acid and vitamin E were negatively associated with the risk (trend p = 0.05 for saturated fatty acid and 0.03 for vitamin E). CONCLUSION: Our study clearly demonstrated that prolonged heavy alcohol consumption was an important and independent risk factor, and suggested a role of lower nutrient intakes in the development of chronic pancreatitis.

Adult↗

Inflammatory pseudotumor of lymph nodes: clinicopathologic and immunohistological study of 11 Japanese cases.

We report 11 Japanese cases of inflammatory pseudotumor (IPT) of the lymph node. There were 7 males and 4 females with ages ranging from 5 to 68 years (median; 48). Only 2 patients had systemic lymphadenopathy, and all others had involvement of only 1 lymph node group. Constitutional symptoms such as fever were present in 8 patients and laboratory abnormalities were detected in 5. All patients recovered and were alive and well after 2 to 180 months (median; 32 months). Histologically, the process mainly involved the connective tissue framework of the lymph node, secondarily spreading into the lymph node parenchyma and the perinodal tissue. It was characterized by a storiform growth pattern of myofibroblasts, marked vascularity with associated vascular lesions, and a polymorphous reactive cellular infiltrate in a collagen-rich stroma. An immunohistochemical study revealed numerous myofibroblasts, histiocytes, and vascular endothelial cells expressing vascular endothelial growth factor (VEGF) in 6 cases. It was suggested that VEGF may be involved, in part, in the induction of the angiogenesis of IPT. Moreover, the present study indicates that follicular dendritic cell sarcoma, nasal T/natural killer cell lymphoma, and anaplastic large cell lymphoma should be added to the differential diagnosis from IPT of the lymph node. Int J Surg Pathol 9(3):207-214, 2001

Adolescent↗

Pharmacokinetic and pharmacodynamic analysis of the antihypercalcemic effect of incadronate disodium in rats.

Incadronate concentrates into the bone as a target organ after intravenous administration of incadronate disodium. Mature osteoclasts has take up incadronate from the bone surface and convert it from an active to an inactive form. As a result, incadronate decreases the plasma calcium concentration by suppressing bone resorption. In this study, the pharmacokinetic and pharmacodynamic (PK/PD) analysis model for ascertaining the antihypercalcemic effects of incadronate disodium was developed in rats. Data on both the concentration of incadronate in bone and that of free calcium in blood after intravenous administration from our previous study were used for analysis. To estimate the concentration in the surface layer of bone, data on the concentration of incadronate in bone after single intravenous administration were analyzed based on the PK model considering three-compartments. The estimated concentrations in the surface layer in bone were applied to the PD model as an input function. The PD model was developed to analyze the changes in the plasma calcium concentration after a single intravenous administration considering an irreversible inhibition of osteoclast activity. The obtained fitted curves were in good agreement with the observed data. The model could explain the long duration of the antihypercalcemic effect of incadronate disodium and should be useful for planning rational dose regimens for effective antihypercalcemic therapy.

Animals↗

Japan collaborative cohort study for evaluation of cancer risk sponsored by monbusho (JACC study).

This paper primarily aimed to overview the rationale for initiating the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho (Ministry of Education, Science, Sports and Culture of Japan) (JACC Study), by comparing socio-demographic and nutritional changes that were witnessed between 1965 and 1990 in Japan, and also to describe the study design, the follow-up conditions as of the end of 1997, and the frameworks for analyzing the data of the lung, stomach, pancreas and gallbladder/bile duct, based on the approximately 8-year follow-up data. For other major sites such as cancers of the large intestine and liver, an analysis will be started in the fiscal year of 2002. This paper secondarily aimed to be cited as the basic information on the JACC Study when several publications are to be based on.

Adult↗

Validity and reliability of single-item questions about physical activity.

The Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho (JACC Study) included in its self-administered questionnaires some single-item questions concerning physical activity. We examined the validity of the questions among 1,730 Japanese adults and the reliability of the questions among 1,075 Japanese adults. The validity of the sports and physical exercise questions was estimated by comparing the self-administered questionnaire responses with the time spent on the activity and the energy expenditure index for the previous 12-month period, elicited by the interviewing method used in the Japan Lifestyle Monitoring Study with a minor modification. The Spearman's rank correlation coefficients ranged from 0.43 to 0.60, showing moderate correlations. On the other hand, test-retest reliability was estimated by comparing the responses from two separate surveys conducted roughly one year apart. Weighted kappa coefficients of sports and physical exercise questions, classified according to sex and age, ranged from 0.39 to 0.56, showing moderate reliability; and those of a question about walking ranged from 0.25 to 0.39, showing fair reliability. We suggest that measuring physical activity level with these single-item questions may be appropriate for establishing baseline data that reflects long-term physical activity in a large-scale cohort study targeting lifestyle-related diseases.

Adult↗

Smoking, alcohol, sleep and risk of idiopathic sudden deafness: a case-control study using pooled controls.

Sudden deafness sometimes has an identifiable cause, but in most cases the cause is unknown (idiopathic sudden deafness). Vascular impairment has been proposed as an aetiological mechanism for this condition, but it is unclear whether traditional cardiovascular risk factors, such as smoking or alcohol intake, are associated with this condition. We accordingly investigated associations of idiopathic sudden deafness with smoking, alcohol intake and sleep duration in a case-control study. Cases were consecutive patients diagnosed with idiopathic sudden deafness between October 1996 and August 1998 at collaborating hospitals in Japan. Controls were obtained from a nationwide database of pooled controls, with matching for age, gender and residential district. Exposure variables were assessed from a self-administered questionnaire. Subgroup analyses were performed using audiometric subtypes of sudden deafness. Data were obtained for 164 cases and 20,313 controls. Increased risks of idiopathic sudden deafness were observed among participants who consumed two or more units of alcohol per day (OR=1.90, 95% CI=1.12-3.21), and among participants who slept less than seven hours per night (OR=1.61, 95% CI=1.09-2.37). The direct association with alcohol intake was particularly strong for the participants with profound hearing loss. There was little evidence of an association with smoking. This study suggests that alcohol intake and short sleep duration might be risk factors for idiopathic sudden deafness.

Alcohol Drinking↗

Oxygen-enhanced MR ventilation imaging of the lung: preliminary clinical experience in 25 subjects.

OBJECTIVE: The purpose of this study was to show the feasibility of oxygen-enhanced MR ventilation imaging in a clinical setting with correlation to standard pulmonary function tests, high-resolution CT, and (81m)Kr ventilation scintigraphy. SUBJECTS AND METHODS: Seven healthy volunteers, 10 lung cancer patients, and eight lung cancer patients with pulmonary emphysema were studied. A respiratory synchronized inversion-recovery single-shot turbo-spin-echo sequence (TE, 16; inversion time, 720 msec; interecho spacing, 4 msec) was used for data acquisition. The following paradigm of oxygen inhalation was used: 21% oxygen (room air), 100% oxygen, 21% oxygen. MR imaging data including maximum mean relative enhancement ratio and mean slope of relative enhancement were correlated with forced expiratory volume in 1 sec, diffusing lung capacity, high-resolution CT emphysema score, and mean distribution ratio of (81m)Kr ventilation scintigraphy. RESULTS: Oxygen-enhanced MR ventilation images were obtained in all subjects. Maximum mean relative enhancement ratio and mean slope of relative enhancement of lung cancer patients were significantly decreased compared with those of the healthy volunteers (p < 0.0001, p < 0.0001). The mean slope of relative enhancement in lung cancer patients with pulmonary emphysema was significantly lower than that of lung cancer patients without pulmonary emphysema (p < 0.0001). Maximum mean relative enhancement ratio (r(2) = 0.81) was excellently correlated with diffusing lung capacity. Mean slope of relative enhancement (r(2) = 0.74) was strongly correlated with forced expiratory volume in 1 sec. Maximum mean relative enhancement had good correlation with the high-resolution CT emphysema score (r(2) = 0.38). The maximum mean relative enhancement had a strong correlation with the distribution ratio (r(2) = 0.77). CONCLUSION: Oxygen-enhanced MR ventilation imaging in human subjects showed regional changes in ventilation, thus reflecting regional lung function.

Adult↗

[Medical cost analysis of neoadjuvant chemotherapy for advanced tongue and oropharyngeal cancer].

We performed a medical cost analysis on the use of neoadjuvant chemotherapy (NAC) in multi-modal treatments for advanced tongue and oropharyngeal cancer. Twenty-two patients with stage III and IV squamous cell carcinoma of the tongue and oropharynx were enrolled in this study. Two courses of NAC with CDDP and 5-FU followed by radiotherapy were performed in 13 patients who showed a partial response or a complete response after the first course of NAC. The doses of radiation were 60 Gy for 4 patients (rad. group), and 72 Gy for 9 patients who received hyperfractionated radiotherapy with simultaneous Carboplatin (HF rad. group). Radical surgery was performed in 9 patients who did not respond to NAC (surg. group). The mean duration of hospital stay was 89.3 days for the rad. group, 92.0 days for the HF rad. group, and 113.3 days for the surg. group. The mean medical cost was 238,700 points for the rad. group, 264,846 points for the HF rad. group, and 459,468 points for the surg. group. The mean amounts and percentages of cost for NAC were 39,473 points and 16.1% for the rad. group, 44,802 points and 16.9% for the HF rad. group, and 23,451 points and 5.1% for the surg. group. The mean amounts of cost for NAC including examination costs and nursing costs for chemotherapy were 130,196 points and 54.5% for the rad. group, 150,046 points and 55.7% for the HF rad. group, and 113,839 points and 24.8% for the surg. group. The cost of NAC accounted for half of the total cost of chemo-radiation treatment for functional preservation. The duration of the hospital stay was prolonged by NAC, which accounted for a quarter of the total cost for the surg. group. Survival benefits are considered in the analysis of treatment cost-effectiveness for head and neck cancers. In the future, QOL, which is defined as the utility achieved as a result of multi-modal treatments, should also be analyzed along with survival benefits. Cost-utility analyses should include quality-adjusted life years, based upon the cost identification results of our analysis for NAC, to evaluate the efficacy of NAC in multi-modal treatments for head and neck cancers.

Antineoplastic Combined Chemotherapy Protocols↗

Acute cytotoxic effects of ethanol on cultured mouse myocardial cells in a monolayer--enzymatic, chronotropic and ultrastructural studies.

The cytotoxicity of ethanol was investigated by detecting the leakage of lactate dehydrogenase (LDH) from three types of cultured mouse cells--non-proliferative but spontaneously and synchronously contracting atrial and ventricular myocardial cells in monolayer sheets, and also proliferative non-muscle fibroblast-like cells--over a 24-hr period (1, 3, 6 and 24 hr) after exposure to ethanol (12.5, 50, 200 and 500 mM). The beat rate and ultrastructure were also investigated. Only a 24-hr exposure to 500 mM ethanol markedly increased LDH leakage from all three types of cells, and it made 20-50% of these cells dead. The rate of spontaneous contractions of ventricular cells transiently increased after a 1-hr exposure to 200 mM ethanol and a 3-hr exposure to 500 mM ethanol compared with the control, though that of atrial cells did not show any significant change but tended rather to dose-dependently cease contracting. Atrial cells exposed to 500 mM ethanol never contracted, while ventricular cells ceased contracting only at 24 hr. After a 24-hr exposure to 500 mM ethanol some cells were necrosed ultrastructually, and the surviving cells contained giant mitochondria being bizarre in shape and many lipid droplets. Thus, ethanol induced cytotoxic effects terminating in death in cultured mouse heart-derived cells at a concentration of 500 mM. However, this concentration of ethanol did not induce any fatal effects within a 6-hr period, and neither did ethanol concentrations of less than 200 mM over a 24-hr period, as confirmed by the continuance of spontaneous contractions and ultrastructural observations.

Animals↗

[Three cases of malignant lymphoma accompanied by renal cell carcinoma].

Three cases of malignant lymphoma (ML) accompanied by renal cell carcinoma (RCC) are reported. From September 1997 through August 2000, we treated 85 patients with ML. Among these patients, three had accompanying RCC (clear cell type): case 1, a 57-yr-old man with gamma/delta-T cell lymphoma; case 2, a 25-yr-old man with Grade 3 follicular lymphoma; case 3, a 64-yr-old man with MALToma of the right orbit. Renal cell carcinoma is a relatively rare disease, but several reports have indicated that, for some reason, the incidence of concurrent RCC and ML is higher than expected. It is possible that the two malignancies share some common background factors, such as genetic mutation, immunological abnormality, or an immunomodulatory effect of the first tumor. The patient in case 2 was thought to have an abnormal immunological background from his medical history, which included bronchial asthma, idiopathic thrombocytopenic purpura, and mesangial proliferative glomerulonephritis (non-IgA type). Therefore the combination of ML and RCC in this patient may have been due to immunological impairment.

Adult↗

[Teratogenicity study of N-methylphenyl-N'-methylphenyl-p-phenylenediamine (MMPD) in rats by oral administration].

Teratogenicity of N-methylphenyl-N'-methylphenyl-p-phenylenediamine (MMPD), a rubber antioxidant, was examined in Wistar rats. MMPD was given to pregnant rats by gavage once a day from day 6 through day 15 of pregnancy at doses of 0, 2, 4 and 8 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy and their fetuses were examined. MMPD was not maternal toxicity at any dose. MMPD did not affect growth or morphological development of fetuses. MMPD caused early embryonic death at 8 mg/kg. It was concluded from these results that the no-observed-adverse-effect level was 2 mg/kg/day for rat fetuses, and 8 mg/kg/day or higher for pregnant rats. The teratogenicity of MMPD was inconclusive due to its embryo-fetal lethality.

Abnormalities, Drug-Induced↗

Inhibition by parthenolide of phorbol ester-induced transcriptional activation of inducible nitric oxide synthase gene in a human monocyte cell line THP-1.

Excessive nitric oxide production by inducible nitric oxide synthase (iNOS) in stimulated inflammatory cells is thought to be a causative factor of cellular injury in inflammatory disease states. Compounds inhibiting iNOS transcriptional activity in inflammatory cells are potentially anti-inflammatory. An assay method for estimating iNOS transcriptional activity in the human monocyte cell line THP-1 was established using a luciferase reporter gene system. In this study, we demonstrate that parthenolide, the predominant sesquiterpene lactone in European feverfew (Tanacetum parthenium), exerts potent inhibitory effects on the promoter activity of the iNOS gene in THP-1 cells. Parthenolide effectively suppressed iNOS promoter activity in a dose-dependent manner at concentrations higher than 2. 5 microM, with an IC(50) of about 10 microM. A tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), significantly increased the iNOS promoter-dependent reporter gene activity, and the TPA-induced increase in iNOS promoter activity was effectively suppressed by parthenolide, with an IC(50) of approximately 2 microM. The present findings may further explain the anti-inflammatory property of parthenolide.

Anti-Inflammatory Agents, Non-Steroidal↗

Extracellular ATP reduces optically monitored electrical signals in hippocampal slices through metabolism to adenosine.

Electrical signals in rat hippocampal slices were optically monitored using a voltage-sensitive dye to determine whether extracellular ATP exhibits direct effects through its own receptors or indirect effects after its hydrolysis to adenosine. The dentate gyrus was stimulated and electrical signals in the CA1 and the CA3 region were analyzed. The signals were divided into two components: a transient component peaking within 10 ms (fast component) and a subsequent sustained component (slow component). ATP (10 to 100 microM) inhibited both the fast and the slow components in the CA1 region by about 30% and 70%, respectively. ADP, AMP and adenosine also inhibited the fast and the slow components. The inhibition by ATP was antagonized by aminophylline and other adenosine receptor antagonists, and by alpha,beta-methylene ADP, an inhibitor of 5'-nucleotidases. These results suggest that extracellular ATP inhibits neuronal electrical signals in hippocampal slices after its metabolism to adenosine.

Adenosine↗

Zic2 regulates the kinetics of neurulation.

Mutation in human ZIC2, a zinc finger protein homologous to Drosophila odd-paired, causes holoprosencephaly (HPE), which is a common, severe malformation of the brain in humans. However, the pathogenesis is largely unknown. Here we show that reduced expression (knockdown) of mouse Zic2 causes neurulation delay, resulting in HPE and spina bifida. Differentiation of the most dorsal neural plate, which gives rise to both roof plate and neural crest cells, also was delayed as indicated by the expression lag of a roof plate marker, Wnt3a. In addition the development of neural crest derivatives such as dorsal root ganglion was impaired. These results suggest that the Zic2 expression level is crucial for the timing of neurulation. Because the Zic2 knockdown mouse is the first mutant with HPE and spina bifida to survive to the perinatal period, the mouse will promote analyses of not only the neurulation but also the pathogenesis of human HPE.

Animals↗

Key amino acids of vasopressin V1a receptor responsible for the species difference in the affinity of OPC-21268.

A non-peptide, vasopressin V1a receptor-selective antagonist, OPC-21268, exhibited a markedly higher affinity for the rat V1a receptor (Ki = 380 nM) than for the human V1a receptor (Ki = 140 microM). To delineate the region responsible for the high affinity binding of OPC-21268 for the rat V1a receptor, we have constructed a series of chimeric human and rat V1a receptors, and examined the chimeric and point-mutated receptors by competitive radioligand binding analysis. The results showed that the transmembrane domain (TMD) VI-VII of the vasopressin V1a receptor, in particular the amino acid residue Ala-342 in TMD VII, is the major component conferring the rat-selective binding of OPC-21268 to the V1a receptor.

Amino Acid Sequence↗