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Biomedical subjects

Y Ohno

Publications and source records attributed to Y Ohno.

At least 217 records · Page 12Linked to original sources
PubMed1998

[Studies on development and improvement of toxicity guidelines conducted at the Biological Safety Research Center].

From FY 1990, studies aimed at development and improvement of toxicity guidelines have been conducted at the Biological Safety Research Center, in collaboration with the Environmental Health Bureau. To date, researches have focused on acute toxicity, antigenicity, reproductive toxicity, immunotoxicity, etc. In this report, brief summary of studies on cytotoxicity, toxicokinetics, neurotoxicity, genetic toxicity and structure-activity relationship performed during FY 1995-97, is presented.

Animals↗
PubMed1998

[Combination chemotherapy with nedaplatin and 5-FU for head and neck cancer].

Nedaplatin (CDGP), which is a CDDP analog, is an effective anticancer agent for head and neck cancer. The first-line chemotherapy for head and neck cancer is reported to be the combination of CDDP and 5-FU. We undertook a clinical trial for combination CDGP and 5-FU to determine whether this chemotherapy has the potential effect of combination with CDDP and 5-FU. First of all, we tried to determine the maximum dose and recommended dose of CDGP in the combination with CDGP and 5-FU by the dose finding regulation method used in combination phase I study. We determined the maximum dose of CDGP as 120 mg/m2, and the recommended dose as 100 mg/m2 with CDGP and 5-FU, 700 mg/m2/day for 5 days. Thirteen cases were treated with CDGP and 5-FU by the recommended dose. Three cases showed CR, and seven cases showed PR. The response rate was 76.9%. Two cases showed hematological toxicity, one grade 3 platelet decreasing and the other grade 3 leucopenia. Two cases showed renal toxicity less than grade 2. Nausea and vomiting were mild. The combination with CDGP and 5-FU seemed to have a strong effect and low toxicity. Further study will be needed to determine the efficacy against head and neck cancer.

Aged↗
PubMed1998

[Increased erythron transferrin uptake associated with ineffective erythropoiesis in iron deficiency state--the common factors to iron deficiency anemia and portal hypertensions].

We calibrated the erythron transferrin uptake (ETU) and efficiency ratio (R-Ef) in erythropoiesis on the basis of ferroerythrokinetic data in 90 patients with iron deficiency anemia (IDA) and 64 patients with noncirrhotic and cirrhotic portal hypertension with splenomegaly (PH). Then we analyzed the data to elucidate how iron deficiency (ID) status effects variation of these values. ETU was significantly higher and R-Ef was lower in IDA subgroup before treatment (n = 71) than those with any recent treatment (n = 19), and in PH with anemia of ID type (PH-ID n = 39) than those without ID state (n = 34). A remarkable inverse correlation was obtained between ETU and R-Ef in both IDA and PH-ID and iron replacement therapy effected synchronous improvement of these values. We deduced the quantitative parameter of ID status (ID-x) on blood chemistry data in IDA by multiple regression of ETU and of R-Ef respectively. These calibration formulae were extrapolated to the data in PH-ID. Thus we delineate the factor which represents ID status in common to these two diseases to increase ETU and decrease R-Ef, although the contribution of ID-x was greater in IDA than PH-ID. Additional factors to enhance or modify these values were shortened survival of erythrocytes, splenomegaly and hepatic dysfunction.

Anemia, Iron-Deficiency↗
PubMed1998

Association of Ile462Val (Exon 7) polymorphism of cytochrome P450 IA1 with lung cancer in the Asian population: further evidence from a case-control study in Okinawa.

Okinawa, a group of islands that lie between the East China Sea and the Pacific Ocean, 2000 km south of the Japanese main islands, has a different profile of diseases, ethnicities, and cultures than does the rest of Japan. We examined an Ile462Val polymorphism (CYP1A1*2 allele) of cytochrome P450 IA1 in a hospital-based case-control study of lung cancer patients (247 cases and 185 controls) in Okinawa to ascertain the association of this variant with lung cancer. In addition, the distribution of this genotype was studied in populations from different areas of Japan, including Tokyo (n = 69) and Iwate (northern part of Japan; n = 81), as well as in a Chinese group from the Jiangsu province (n = 39) and in an Australian Caucasian group (n = 146). Genotype frequency in controls was not significantly different from area to area in Japan. In Okinawa, however, the genotype encoding Val/Val was associated with a significantly higher risk of lung cancer (odds ratio = 3.32, P = 0.013), especially of squamous cell carcinoma and small cell carcinoma (odds ratio = 4.85 and 9.35, respectively). The Val-encoding allele was less frequent in the Chinese population and was rare in Australian Caucasians. Thus, this study gives support to the value of the cytochrome P450 IA1 Ile462Val polymorphism as a practical high-risk marker of lung cancer in populations, especially those in southeast Asia, in which this variant is more common.

Adult↗
PubMed1998

[Assessment method for supporting programs for social activities of the elderly by city, town and village governments in Japan].

OBJECTIVES: The authors developed a questionnaire to assess the activities of supporting programs for social activities for the elderly conducted by city, town and village governments, based on the number of such programs. This study aims to examine the validity of the questionnaire. METHODS: We conducted a study of 145 cities, towns and villages from two prefectures in Japan using the questionnaire. The questionnaire asks government officers whether they had each of 32 programs, and the number of programs in total, as well as each of four domains of social activities (i.e., employment, social participation/volunteering, education/training, individual activities) were calculated. They were also asked to classify each of the programs into one of four domains of social activity to which the programs were most related; they were asked to rate how active the programs were for each domain in their community. To examine the validity of the questionnaire, the following indicators were assessed: (1) proportion of reported programs which were not covered by the questionnaire; (2) concordance of classification of programs into four domains of social activity with those judged by government officers; (3) correlations between number of programs and self-rated activity levels by government officers; and (4) correlations of number programs with characteristics of cities, towns or villages. RESULTS: The results indicated that the list of programs covered most of the programs. Proposed classification of programs into four domains of social activities which they are most related to agreed with judgments by officials. The number of programs positively correlated with self-rated activity levels by officers for employment and education/training domains in both prefectures; and for social participation/volunteering and individual activities in one of the prefecture. The numbers of programs for employment of the elderly positively correlated with the total population of the community, number of staffs, proportion of people employed in the tertiary industries and total budget for social welfare of the elderly; it negatively correlated with proportion of people employed in the primary industries. CONCLUSION: It is suggested that the list of programs in the questionnaire is applicable and assessment based on the number of programs by four social activity domains is valid to some extent in either prefecture. The questionnaire can be improved further, e.g., by adding other programs to the list.

Aged↗
PubMed1998

[Basic study of MR-dacryocystography].

We developed MR-dacryocystography as a non-invasive, safer imaging technique for canaliculi, the nasolacrimal duct and lacrimal sac by dropping saline solution and diluted Gd-DTPA solution into the eye. The diluted Gd-DTPA solution was found to create no local irritation in the eyes of rabbits and normal volunteers. Lacrimal sacs and ducts were well visualized in all of 10 normal volunteers by using the saline solution or the diluted Gd-DTPA solution. Canaliculi were visualized in 4-7 cases on thin-slice axial images. MR-dacryocystography was suggested to be a useful screening examination for lacrimal outflow disorders.

Adult↗
PubMed1998

Newly developed diabetic retinopathy and its preceding changes in biological markers.

To disclose the chronological changes prior to the manifestation of diabetic retinopathy (DR), we analyzed the time course of biological markers among apparently healthy diabetic subjects in a case-control study of 21,579 adults who had undergone comprehensive health examinations for > or = 10 years. We identified 54 cases who had newly developed DR, and selected 108 adults without fundus abnormalities, matching them for sex, age, and fasting plasma glucose (FPG) at the onset of the patient group's retinopathy as a referent group from the same population. In a multivariate analysis, a high average FPG (> 175 mg/dl) and a final-year FPG reduction (< -3%) were significantly associated with a 5.4 (95% CI, 1.8-15.7)- and 5.0 (95% CI, 1.0-24.7)-fold increased risk of DR, respectively. Thus, we surmised that sustained hyperglycemia and a subsequent drop in FPG might promote retinopathy in non-insulin dependent diabetes mellitus.

Biomarkers↗
PubMed1998

Influence of the allergic response on the mucociliary system in the eustachian tube.

The effect of systemic and local allergic responses on the mucociliary system of the Eustachian tube was investigated. Egg albumin was administered to guinea pigs via the jugular vein to evoke systemic anaphylaxis in animals previously sensitized with egg albumin. Ciliary activity in the Eustachian tube of sensitized animals was significantly higher than that of control animals. However, the mucociliary clearance time of the Eustachian tube in sensitized animals was significantly longer than in control animals. Local allergic response induced by intratympanic instillation of (BPO)61-BGG induced cilioexcitation and prolonged mucociliary clearance in the guinea pigs sensitized with BPO-BGG. A partial loss of the inner layer of the mucus blanket of the Eustachian tube was observed under electron microscopy. In conclusion, the systemic as well as the local allergic response accelerates ciliary activity but may affect the mucus blanket and induce mucociliary dysfunction in the Eustachian tube, resulting in a predisposition to middle ear diseases.

Allergens↗
PubMed1998

Risk factors for adverse systemic reactions occurring during immunotherapy with standardized Dermatophagoides farinae extracts.

The most serious problem in practical immunotherapy is the risk of occasional, potentially life-threatening adverse systemic reactions. Elucidation of the incidence of, and possible risk factors for, systemic reactions would have a profound effect on the decision about how to manage allergic rhinitis. The aim of this retrospective study was to document the incidence and risk factors of adverse systemic reactions during immunotherapy using standardized Dermatophagoides farinae (D. farinae) extracts for perennial allergic rhinitis. This study included 386 patients (22,722 injections) with perennial allergic rhinitis who had received immunotherapy with standardized D. farinae extracts in our clinics for the past 5 years. The incidence of systemic reactions was 6.22% per patient and 0.12% per injection. The time of onset of systemic reactions ranged from 3 to 30 min (mean 11.3 min) after injections. Our study has demonstrated that asthma, atopic dermatitis and a high level of IgE in serum, but not a high level of specific IgE in serum, are important high risk factors that may induce severe adverse systemic reactions in patients who receive immunotherapy for perennial allergic rhinitis. The incidence of systemic reactions in those who had a high level of IgE (higher than 1000 U/ml) and asthma and/or atopic dermatitis was 66.67% (12/18) per patient. Conversely, the incidence of systemic reactions in those who had none of the risk factors was 1.64% per patient. Thus, the rate of systemic reactions is thought to be reduced by 75% if patients with high risk factors are strictly excluded from immunotherapy for allergic rhinitis.

Allergens↗
PubMed1998

Nitrogen dioxide modifies allergic inflammation in tracheal mucosa.

Our study was designed to investigate the possible role of nitrogen dioxide exposure in respiratory allergic disorders. Guinea pigs were treated with a combination of passive sensitization, antigen challenge and nitrogen dioxide exposure. Nitrogen dioxide accumulated eosinophils to the epithelium of the trachea. Neither passive sensitization nor antigen challenge with nitrogen dioxide exposure developed more prominent pathological changes than nitrogen dioxide exposure alone. However, antigen--antibody interaction with nitrogen dioxide exposure resulted in a disruption of epithelial cells so prominent that the basement membrane was denuded in areas. Activated eosinophils and free eosinophil-specific granules were considered to be responsible for the extreme epithelial injury. In conclusion, nitrogen dioxide exposure does not cause prominent epithelial injury by itself, but could be a trigger for hyperresponsiveness in allergic airways, and is probably involved in the pathogenesis of airway allergic disorders.

Air Pollutants↗
PubMed1998

[MR images of mycobacterial infection].

With the progress of imaging technologies such as CT and MR imaging, we can obtain various informations from CT and MR images. Especially, thin-section high resolution CT (HRCT) provides very useful information for the diagnosis of mycobacterial infection and other diseases of pulmonary parenchyma. Advantages of MR images over HRCT are higher tissue contrast and multidirection capability. The T2-weighted images and Gd-DTPA enhanced T1-weighted images accurately reflect pathologic structure of the lesion. Therefore, MR images can add many useful findings to CT on the selected cases which are differentiation of tubercloma from lung cancer, chronic empyema from mesothelioma, aspergiloma from lung cancer and lymphadenopathy from lymph node metastasis. We describe the usefulness of MR images for diagnosing mycobacterial infection and its differentiation from other pulmonary diseases.

Diagnosis, Differential↗
PubMed1997

Nicorandil reduces myocardial infarct size by opening the K(ATP) channel in rabbits.

UNLABELLED: We examined whether nicorandil reduces myocardial infarct size (1) when administered before ischemia, and (2) when administered before reperfusion, and whether (3) infarct size is influenced by the plasma nicorandil concentration and the opening of the K(ATP) channel. Anesthetized open-chest Japanese white male rabbits were subjected to a 30 min coronary occlusion (ischemia) and a 48 h reperfusion in the following six groups; Group 1 (n=9): control group, Group 2 (n=9): pre-ischemia to post-reperfusion group (nicorandil 10 microg/kg/min, i.v.), Group 3 (n=7): pre-ischemia to post-reperfusion+glibenclamide group (glibenclamide 0.3 microg/kg, i.v.+nicorandil 10 microg/kg/min, i.v.), Group 4 (n=8): pre-reperfusion to post-reperfusion group (nicorandil 10 microg/kg/min, i.v.), Group 5 (n=8): pre-ischemia low-dose group (nicorandil 10 microg/kg/min for 5 min i.v.), Group 6 (n=7): pre-ischemia high-dose group (nicorandil 100 microg/kg/min for 5 min i.v.). The plasma nicorandil concentrations were measured from blood samples taken immediately before the ischemia. After the 48 h reperfusion, the size of the infarct was measured histologically with immunohistochemical actin staining and expressed as a percentage of the area at risk. RESULTS: Infarct sizes were as follows; Group 1 (control): 41.0+/-3.5%, Group 2: 31.3+/-2.0% (P<0.05 vs. control), Group 3: 40.9+/-3.4%, Group 4: 45.2+/-4.4%, Group 5: 35.8+/-3.3%, Group 6: 25.2+/-3.9% (P<0.05 vs. control). Infarct size was inversely correlated with the plasma nicorandil concentrations (y=-0.031x+41.0, r=0.65, P<0.05). CONCLUSIONS: The pre-ischemic but not post-ischemic administration of nicorandil reduced the size of myocardial infarct by opening the K(ATP) channels, and this effect was dependent on the plasma nicorandil concentrations immediately before the ischemia induced in rabbits.

Analysis of Variance↗
PubMed1997

pH dependence of facilitation by neurotransmitters and divalent cations of P2X2 purinoceptor/channels.

The pH dependence of the facilitation by dopamine (10 microM), 5-hydroxytryptamine (10 microM), adenosine (1 and 100 microM), Zn2+ (10 microM) and Cd2+ (1 mM) of P2X2 purinoceptor/channels was tested by expressing these channels in Xenopus oocytes. In a pH range between 6.0 and 8.5, concentration-response curves for an inward current activated by ATP were shifted toward a lower concentration range at a more acidic pH, indicating that the sensitivity to ATP is pH-dependent. Comparison of the effects of the neurotransmitters and the divalent cations on the ATP-activated current was made using a concentration of ATP which activated 40-50% of the maximal current at each pH value. The current facilitation by dopamine was obvious at pH 7.1 and 7.7, but was not observed at pH 8.5. At pH 6.0, the current was inhibited upon first trials of dopamine, but it was facilitated upon second trials. With 5-hydroxytryptamine and adenosine, the current facilitation was most remarkable at pH 6.0, less remarkable at pH 7.1 and 7.7, and the facilitation was almost abolished at pH 8.5. On the other hand, the current facilitation by Zn2+ and Cd2+ was more remarkable at alkaline pH values (7.7 and 8.5), and the facilitation was almost abolished at pH 6.0. The results suggest that the facilitation of P2X2 purinoceptors depends on pH, and the pH dependence was different between the neurotransmitters and the divalent cations.

Adenosine↗
PubMed1997

Cellular mechanisms mediating rat renal microvascular constriction by angiotensin II.

To assess cellular mechanisms mediating afferent (AA) and efferent arteriolar (EA) constriction by angiotensin II (AngII), experiments were performed using isolated perfused hydronephrotic kidneys. In the first series of studies, AngII (0.3 nM) constricted AAs and EAs by 29+/-3 (n = 8, P < 0.01) and 27+/-3% (n = 8, P < 0.01), respectively. Subsequent addition of nifedipine restored AA but not EA diameter. Manganese (8 mM) reversed EA constriction by 65+/-9% (P < 0.01). In the second group, the addition of N-ethylmaleimide (10 microM), a Gi/Go protein antagonist, abolished AngII- induced EA (n = 6) but not AA constriction (n = 6). In the third series of experiments, treatment with 2-nitro-4-carboxyphenyl-N, N-diphenyl-carbamate (200 microM), a phospholipase C inhibitor, blocked both AA and EA constriction by AngII (n = 6 for each). In the fourth group, thapsigargin (1 microM) prevented AngII-induced AA constriction (n = 8) and attenuated EA constriction (8+/-2% decrease in EA diameter at 0.3 nM AngII, n = 8, P < 0.05). Subsequent addition of manganese (8 mM) reversed EA constriction. Our data provide evidence that in AAs, AngII stimulates phospholipase C with subsequent calcium mobilization that is required to activate voltage-dependent calcium channels. Our results suggest that AngII constricts EAs by activating phospholipase C via the Gi protein family, thereby eliciting both calcium mobilization and calcium entry.

Angiotensin II↗
PubMed1997

Macrophage inflammatory protein-2: chromosomal regulation in rat small intestinal epithelial cells.

Nonpathogenic, resident bacteria participate in the pathogenesis of inflammation in the small intestine, but the molecular messages produced by such bacteria are unknown. Inflammatory responses involve the recruitment of specific leukocyte subsets. We, therefore, hypothesized that butyrate, a normal bacterial metabolite, may modulate chemokine secretion by epithelial cells, by amplifying their response to proinflammatory signals. We studied the expression of the chemokine, macrophage inflammatory protein-2 (MIP-2) by the rat small intestinal epithelial cell line, IEC-6. Cells were stimulated with lipopolysaccharide or with interleukin 1beta (IL-1beta) and incubated with sodium butyrate. Acetylation of histones was examined in Triton X acetic acid-urea gels by PAGE. Unstimulated IEC-6 cells did not secrete MIP-2. However, lipopolysaccharide and IL-1beta induced MIP-2 expression. Butyrate enhanced MIP-2 secretion both in lipopolysaccharide-stimulated and IL-1beta-stimulated enterocytes; but butyrate alone did not induce MIP-2 expression. Butyrate increased the acetylation of histones extracted from the nuclei of IEC-6 cells. Furthermore, acetylation of histones (induced by trichostatin A, a specific inhibitor of histone deacetylase) enhanced MIP-2 expression by cells stimulated with IL-1beta. In conclusion, trichostatin A reproduced the effects of butyrate on MIP-2 secretion. Butyrate, therefore, increases MIP-2 secretion in stimulated cells by increasing histone acetylation. We speculate that butyrate carries information from bacteria to epithelial cells. Epithelial cells transduce this signal through histone deacetylase, modulating the secretion of chemokines.

Acetylation↗
PubMed1997

Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell proliferation and phosphatidylinositol 3-kinase activity.

The vav proto-oncogene product (Vav), which is specifically expressed in hematopoietic cells, contains multiple structural motifs commonly used by intracellular signaling molecules. Although a variety of stimuli including erythropoietin (Epo) have been shown to tyrosine phosphorylate Vav, little is known about the Vav signal transduction pathway. Here, we have investigated the role of Vav in the Epo signaling pathway by characterizing its interaction with other proteins, using the human Epo-responsive cell line, F-36P. Immunoprecipitation and immunoblot analyses have demonstrated that Vav was associated with the Epo receptor (EpoR) in an Epo-independent manner and was tyrosine-phosphorylated after Epo stimulation. Furthermore, two phosphotyrosine proteins (pp70 and pp100) co-immunoprecipitated with the regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase) (p85) were identified as EpoR and Vav, respectively. The interaction between Vav and p85 was shown to be mediated through the SH2 domains of p85 by an in vitro binding assay and confirmed by the presence of in vitro PI3-kinase activity associated with Vav. Treatment of the cells with antisense-vav and -p85 abrogated Epo-induced cell proliferation and PI3-kinase activity. Finally, we found that JAK2 was associated with Vav in vivo and that Vav could be tyrosine-phosphorylated by activated JAK2 in vitro. These results suggest the possible role of JAK2 for tyrosine phosphorylation of Vav and involvement of Vav and PI3-kinase in Epo-induced proliferative signals.

Cell Cycle Proteins↗
PubMed1997

Potent inhibition by trivalent cations of ATP-gated channels.

The effects of La3+ and other trivalent cations on ATP-gated channels (P2X purinoceptor/channels) were investigated using rat pheochromocytoma PC12 cells and Xenopus oocytes expressing these channels. La3+, Gd3+, Ce3+ and Nd3+ (30-300 microM) inhibited an inward current activated by 30 microM ATP in PC12 cells. The concentration-response curve for the ATP-activated current was shifted by La3+ or Gd3+ toward a higher concentration range, and the slope of the curve became steeper, suggesting the inhibition is non-competitive. La3+ or Gd3+ did not affect the current component that was slowly activated upon hyperpolarization, and selectively inhibited the remaining 'voltage-independent' component. La3+ and Gd3+ also inhibited currents mediated through P2X1 and P2X2 purinoceptors expressed in Xenopus oocytes. The results suggest that La3+ and other trivalent cations inhibit P2X purinoceptors at low concentrations. The inhibition may at least partly be attributed to an allosteric inhibition.

Adenosine Triphosphate↗