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Biomedical subjects

T Yoshimura

Publications and source records attributed to T Yoshimura.

At least 37 records · Page 2Linked to original sources
PubMed2002

A prospective study of stomach cancer death in relation to green tea consumption in Japan.

To evaluate whether green tea consumption provides protection against stomach cancer death, relative risks were calculated using Cox proportional hazards regression analysis in the Japan Collaborative Study for Evaluation of Cancer Risk, sponsored by the Ministry of Health and Welfare (JACC Study). The study was based on 30 370 men and 42 481 women aged 40-79. After adjustment for age, smoking status, history of peptic ulcer, family history of stomach cancer along with certain dietary items, the risks associated with drinking one or two, three or four, five to nine, and 10 or more cups of green tea per day, relative to those of drinking less than one cup per day, were 1.6 (95% CI: 0.9-2.9), 1.1 (95% CI: 0.6-1.9), 1.0 (95% CI: 0.5-2.0), and 1.0 (95% CI: 0.5-2.0), respectively, in men (P for trend=0.669), and 1.1 (95% CI: 0.5-2.5), 1.0 (95% CI: 0.5-2.5), 0.8 (95% CI: 0.4-1.6), and 0.8 (95% CI: 0.3-2.1), respectively, in women (P for trend=0.488). We found no inverse association between green tea consumption and the risk of stomach cancer death.

Adult↗
PubMed2002

Dietary factors and stomach cancer mortality.

The present study examined the relationship between stomach cancer and the low intake of fresh fruit and vegetables and/or a high intake of pickled, preserved or salted foods and frequent use of cooking oil. During 139,390 person-year of follow-up of over 13,000 subjects, 116 died from stomach cancer. Using a Cox proportional hazards-regression analysis of relative risk (RR, 95% CI) controlling for age, sex, smoking and other dietary factors, a significant decline was found with a high consumption of green and yellow vegetables (RR=0.4, 95% CI=0.2-0.9). Reductions of between 40 and 50% were also observed with a high consumption of fresh foods (fruit, cuttle fish, tofu, and potatoes), but these associations were not statistically significant. The risk was significantly increased by the high consumption of processed meat (RR=2.7, 95% CI=1.0-7.4) and by the frequent use of cooking oil (RR=4.0, 95% CI=1.3-11.8). The high consumption of pickled food and traditional soups also increased risk, but not significantly. The findings suggest that a diet high in salt and low in vitamins may be associated with an increase in stomach cancer.

Adolescent↗
PubMed2002

Cimetidine modulates the antigen presenting capacity of dendritic cells from colorectal cancer patients.

Cimetidine, a H(2) receptor antagonist, has been reported to improve survival in gastrointestinal cancer patients. These effects have largely been attributed to the enhancing effects of cimetidine on the host's antitumour cell-mediated immune response, such as inhibition of suppressor T lymphocyte activity, stimulation of natural killer cell activity and increase of interleukin-2 production from helper T lymphocytes. We conducted an in vitro study on the effects of cimetidine on differentiation and antigen presenting capacity of monocyte-derived dendritic cells from advanced colorectal cancer patients and normal controls. As a result, an investigation of expression of surface molecules associated with dendritic cells by flow cytometric analyses showed that cimetidine had no enhancing effect on differentiation of dendritic cells from cancer patients and normal controls. An investigation of [(3)H]thymidine incorporation by allogeneic mixed lymphocyte reactions revealed that cimetidine increased the antigen presenting capacity of dendritic cells from both materials. Moreover, a higher antigen presenting capacity was observed in advanced cancer patients compared to normal controls. These effects might be mediated via specific action of cimetidine and not via H(2) receptors because famotidine did not show similar effects. Our results suggest that cimetidine may enhance the host's antitumour cell-mediated immunity by improving the suppressed dendritic cells function of advanced cancer patients.

Adult↗
PubMed2002

A prospective study of blood transfusion history and liver cancer in a high-endemic area of Japan.

BACKGROUND: The high prevalence of liver cancer in Japan may be owing to infection with hepatitis C virus (HCV), for which the major transmission route is blood transfusion. However, among the general population, there have been few follow-up studies of people with a history of transfusion. The purpose of this study was to examine whether such a history correlates with the development of liver cancer among the general population of this high-endemic area. STUDY DESIGN AND METHODS: The baseline survey was conducted between 1986 and 1991 among the population (15,597 people, aged 30-79) of Fukuoka prefecture, Japan. The participants were assessed for their transfusion history and other covariates using a baseline questionnaire. The relative risk (RR) of blood transfusion for liver cancer was estimated using the Cox proportional hazard model. RESULTS: The RRs of transfusion for subsequent liver cancer were 1.86 (95% confidence interval (CI) = 1.05-3.29) in men and 4.20 (95% CI = 1.83-9.61) in women, after adjusting for covariates. Transfusion was associated with an increased risk of liver cancer, mainly in the group without hepatitis and cirrhosis (RR = 1.81, 95% CI = 0.84-3.91 - men; RR = 4.39, 95% CI = 1.37-14.02 - women). CONCLUSION: A history of blood transfusion carried a significant risk of developing liver cancer in the study region. The people with a history of transfusion should be monitored more aggressively for viral infections and liver disease, as they may not report the infection or they may be unaware that they are infected.

Adult↗
PubMed2002

A novel sialyl Lewis(x) analogue attenuates ischemia reperfusion injury in rabbit lung.

BACKGROUND: We investigated the effects of OJ-R9545, a novel Sialyl Lewis x analogue, on lung ischemia-reperfusion (IR) injury using an in vivo rabbit model. METHODS: The left hilum of the lung was clamped for 110 minutes; the lung was then reperfused for 90 minutes. Either OJ-R9545 (10 mg/kg) or vehicle solution was administered from 10 minutes before reperfusion to 60 minutes after reperfusion in the OJ-R (+) and OJ-R (-) group (n = 6 in each group), respectively. The sham group (n = 3) underwent an identical procedure without ischemia. RESULTS: Arterial oxygen tensions in the OJ-R (+) group were superior to those in the OJ-R (-) group from 30 to 90 minutes after reperfusion (p < 0.05 and p < 0.01). Lung wet/dry weight ratio and myeloperoxidase activity after reperfusion in the OJ-R (+) group were both significantly lower than the corresponding figures in the OJ-R (-) group (p < 0.05). The intrapulmonary leukocytes were significantly reduced in the OJ-R (+) group compared with those in the OJ-R (-) group (p < 0.01). CONCLUSIONS: OJ-R9545 attenuates lung IR injury by preventing leukocyte infiltration into the lung.

Animals↗
PubMed2001

Anchoring and bola cationic amphiphiles for nucleotide delivery. Effects of orientation and extension of hydrophobic regions.

Novel cationic amphiphiles, based on lithocholic acid derivatives with two structural motifs, anchoring lipids and bola lipids, were designed and synthesized. Both bear extended hydrophobic space-filling substituents. A significant effect of the orientation and extension of hydrophobic regions around the ether linkage at the 3-position was found on the efficiency of DNA delivery.

3T3 Cells↗
PubMed2001

Octa(mu3-selenido)hexarhenium(III) complexes containing axial monodentate diphosphine or diphosphine-monoxide ligands.

A series of the octahedral hexarhenium(III) complexes containing a variable number of diphosphine (diphos) or diphosphine-monoxide (diphosO) ligands have been prepared by the substitution of the diphosphine Ph2P(CH2)nPPh2 (n = 1 to 5) for the iodide ions in the parent octahedral hexarhenium cluster compound [Re6Se8I6]3-. The diphosphine Ph2P-(CH2)nPPh2 ligands adopt an eta1-bonding mode with the Re6(mu3-Se)8 core, and the P donor atom in the pendant arm is noncoordinated and oxygenated in most cases. The series of new hexarhenium(III) complexes have been well-defined by 1H, 13C, and 31P NMR spectroscopic and FAB-MS data. Four compounds among the series were characterized by X-ray structural determination. Geometrical isomers were identified by NMR spectroscopy as well as by the structural determinations. The apical ligand substitution induces significant change in the redox potentials and the photophysical properties of the Re6(mu3-Se), core. The E1/2 value of the reversible process ReIII6/ReIII5ReIV becomes more positive with the increasing number of the coordinated P donors. The phosphine-substituted hexarhenium(III) derivatives are highly luminescent, with microsecond scale emissive lifetime at ambient temperature, and the fully substituted derivatives with the formula [Re6Se8-(eta1-diphosO)6]2+ display the strongest luminescence with the longest emission lifetimes.

Journal Article↗
PubMed2001

Discoidin domain receptor 1 isoform-a (DDR1alpha) promotes migration of leukocytes in three-dimensional collagen lattices.

Although integrins are crucial for migration of leukocytes through endothelium, integrin-independent mechanisms appear to take over and mediate the migration of leukocytes through extracellular matrix (ECM) in a three-dimensional tissue microenvironment. Discoidin domain receptor (DDR) 1 is a receptor tyrosine kinase activated by collagen, the most abundant ECM protein. In the present study, we detected that peripheral blood mononuclear cells (PBMC) and polymorphonuclear neutrophils were induced to express DDR1 after incubation in RPMI 1640. The expression level of DDR1 in PBMC was increased further by stimulation with tumor necrosis factor-alpha, interleukin-1beta, granulocyte-macrophage colony-stimulating factor, lipopolysaccharide, or phytohemagglutinin, but not with interferon-gamma. In vivo, DDR1 mRNA was detectable in mononuclear leukocytes infiltrating human renal tumor tissue. Among three DDR1 isoforms, DDR1alpha was the major transcript in leukocytes. Functionally, overexpression of either DDR1alpha or DDR1beta in THP-1 cells resulted in increased adherence to collagen-coated plates in a beta1-integrin independent manner. However, only DDR1alpha-, but not DDR1beta-, overexpressing cells exhibited marked pseudopod extension and migrated successfully through three-dimensional collagen lattices. Consequently, we propose that the interaction of DDR1alpha with collagen of the ECM results in a requisite intracellular signaling that enables leukocytes to migrate in a tissue microenvironment and participate in host defense.

Blotting, Northern↗
PubMed2001

Short term oral estriol treatment restores normal premenopausal vaginal flora to elderly women.

OBJECTIVE: Estriol is an estrogen with considerably weaker stimulatory effects on endometrial proliferation than estradiol. A study was conducted to determine the effects of oral estriol on vaginal flora and endometrial thickness. METHODS: Fifty-nine postmenopausal women (50-75 years of age), complaining of pruritus or vaginal discharge, participated in the study. Vaginal flora and endometrial thickness were evaluated before treatment and after receiving oral estriol (2 mg/day) for 14 days. RESULTS: Prior to treatment, lactobacilli were found in vaginal cultures from only six of the 59 study participants, whereas after treatment, the vaginal flora of 27 women showed a presence of lactobacilli (P<0.0001). Endometrial thickness exceeded 5 mm in only five cases. No side effects were reported. CONCLUSION: Estriol, which has little effect on the endometrium, has the potential to be highly useful for the treatment of atrophic vaginitis.

Administration, Oral↗
PubMed2001

Optimal alveolar oxygen concentration for cold storage of the lung.

BACKGROUND: Ischemia of the lung is different from that of solid organs because the lung contains gas in the alveoli. However, the optimal gas composition in the alveoli during cold storage remains uncertain. We investigated the relationship between the alveolar oxygen concentration and reperfusion injury. METHODS: The lungs inflated with 0% O2, 5% O2, room air, 50% O2, or 100% O2 were reperfused after 8 hR storage at 4 degrees C and pulmonary functions were measured for 120 min using an ex vivo rat lung model. The levels of high-energy phosphate and lipid peroxidation of the lung were analyzed after a PA flush, preservation, and reperfusion. Additionally, respiration of the mitochondria in the lungs was measured after preservation. RESULTS: The pulmonary functions were significantly superior in the 5% O2 group than those in the 0% O2, 50% O2, and 100% O2 groups. Pulmonary edema developed in the 0% O2, 50% O2, and 100% O2 groups, but not in the 5% O2 group. After preservation, the energy level in the lungs decreased only in the 0% O2 group. Although lipid peroxidation of the lungs did not increase in any group after preservation, significant increases were observed in the room air, 50% O2 and 100% O2 groups after reperfusion. State 3 and 4 ratios of the mitochondrial respiration significantly decreased in the lungs of the room air, 50% O2 and 100% O2 groups. CONCLUSIONS: Although the cold-preserved lungs require oxygen, hyperoxygenation induced mitochondrial dysfunction and increased lipid peroxidation and led to deleterious lung function after reperfusion. Therefore, hypoxic conditions that can maintain the energy level of the lung during cold storage would be optimal.

Adenine Nucleotides↗
PubMed2001

(2-Aminoethanethiolato-N,S)bis(ethylenediamine-N,N')cobalt(III) dinitrate.

In the title compound, [Co(C(2)H(6)NS)(C(2)H(8)N(2))(2)](NO(3))(2), the Co(III) atom has a slightly distorted octahedral geometry, coordinated by one 2-aminoethanethiolate and two ethylenediamine ligands. The three five-membered chelate rings adopt a gauche conformation with the unfavoured (lel)(2)(ob) form, which is ascribed to hydrogen bonds between the amine groups in the complex cation and the nitrate counter-anions [N.O 2.900 (3)-3.378 (3) A].

Journal Article↗
PubMed2001

Targeting antigen-specific receptors on B lymphocytes to generate high yields of specific monoclonal antibodies directed against biologically active lower antigenic peptides within presenilin 1.

We describe a targeting technique that selects antigen-specific receptors on B lymphocytes using antigen driven selective production of monoclonal antibodies which are directed against functional peptide sequences within the presenilin 1 molecule that is believed to be related to the early-onset of familial Alzheimer's disease. Three different peptide sequences of presenilin 1 were constructed, one including the region around the amino acid position 300, where the putative cleavage site exists and the other two present in the N- and C-terminal regions of that site. The efficiency in production of the desired monoclonal antibodies was at least 5-40-fold that obtained with the poly(ethylene glycol) (PEG)-mediated method. In addition, monoclonal antibodies directed against each of the peptide sequence displayed a high specificity for the corresponding peptide, in contrast to the lack of success using the PEG method. Also, the selection of surface immunoglobulin receptors on B lymphocytes by the peptides of interest was confirmed by immunofluorescent analysis. Here we demonstrate that targeting B lymphocytes results in the successful and efficient production of highly specific monoclonal antibodies against the lower antigenic peptide sequences.

Animals↗
PubMed2001

Synthesis, structure-activity relationships, and pharmacokinetic profiles of nonpeptidic alpha-keto heterocycles as novel inhibitors of human chymase.

We designed nonpeptidic chymase inhibitors based on the structure of a peptidic compound (1) and demonstrated that the combination of a pyrimidinone skeleton as a P3-P2 scaffold and heterocycles as P1 carbonyl-activating groups can function as a nonpeptidic chymase inhibitor. In particular, introduction of heterobicycles such as benzoxazole resulted in more potent chymase-inhibitory activity. Detailed structure-activity relationship studies on the benzoxazole moiety and substituents at the 2-position of the pyrimidinone ring revealed that 2r (Y-40079) had the most potent chymase-inhibitory activity (K(i) = 4.85 nM). This compound was also effective toward chymases of nonhuman origin and showed good selectivity for chymases over other proteases. Pharmacokinetic studies in rats indicated that 2r was absorbed slowly after oral administration and showed satisfactory bioavailability (BA) (T(max) = 6.0 +/- 2.3 h, BA = 19.3 +/- 6.6%, t(1/2) = 35.7 +/- 13.3 h). In conclusion, 2r is a novel, potent, and orally active chymase inhibitor which would be a useful tool in elucidating the pathophysiological roles of chymase.

Animals↗
PubMed2001

Synthesis, structure-activity relationships, and pharmacokinetic profiles of nonpeptidic difluoromethylene ketones as novel inhibitors of human chymase.

Potent human chymase inhibitors with high enzymatic selectivity and satisfactory metabolic stability were obtained by replacing the Val-Pro (P3-P2) dipeptide portion of the previously described inhibitor 1 with a nonpeptidic pyrimidinone skeleton. The potency of the novel compounds was further enhanced by the introduction of carbamoyl-substituted difluoromethylene ketone moieties. The most potent chymase inhibitor of the newly created series was 2u (Y-40018), which had a K(i) of 2.62 nM. Compound 2u possessed high selectivity for human chymase since it lacked significant activity toward other representative human proteolytic enzymes. Moreover its strict specificity for human chymase suggested that 2u strongly inhibited human and canine chymases but not rat and mouse ones. Pharmacokinetic studies in rats and dogs indicated that 2u was absorbed rapidly after oral administration and had satisfactory bioavailability in these experimental animal species (rat, 17%; dog, 32%). In conclusion, 2u is a novel, potent, and orally active chymase inhibitor which would prove very useful in revealing the precise roles of the latter in various pathophysiological processes.

Animals↗
PubMed2001

Time trend analysis of gastric cancer incidence in Japan by histological types, 1975-1989.

Since different histological types (HT) of gastric cancer (GC) may differ in their aetiology, time trend analysis by HT may afford an insight into aetiology. From the Gastric Cancer Registry of Japan, 161 067 cases diagnosed were retrieved between 1975 and 1989 to calculate the annual relative frequencies, stratified by age group and sex, of HT according to the Lauren and the Japanese Research Society for Gastric Cancer (JRSGC) classifications. Age- and sex-specific incidence rates by HT were estimated by multiplying the corresponding national cancer incidence rates of GC by the relative frequencies. Logistic regression models stratified by sex and age group were fitted to determine the time trends of HT. Using the Lauren classification, a decreasing trend of the intestinal type and a stable trend of the diffuse type were found. By the JRSGC classification, significant decreasing trends for most age groups were found for papillary and mucinous adenocarcinomas. Tubular adenocarcinomas (well differentiated type) showed a decreasing trend only in younger age groups. Tubular (moderately differentiated type), poorly differentiated adenocarcinomas, and signet ring cell carcinoma were statistically stable during the period. Considering changes in lifestyles of the Japanese, the result suggests that there are three aetiological types of GC.

Adult↗
PubMed2001

Effect of medroxyprogesterone acetate plus estradiol on endothelium-dependent vasodilation in postmenopausal women.

The addition of medroxyprogesterone acetate (MPA) is widely accepted to remove the endometrial-cancerogenic effect of estrogen replacement therapy in postmenopausal women. To evaluate the effect of MPA on endothelial function, we measured flow-mediated vasodilation of brachial arteries after transient occlusion in a randomized, double-blind, placebo-controlled study; we concluded that the addition of MPA attenuates the favorable effects of estradiol on endothelium-dependent vasodilation.

Brachial Artery↗
PubMed2001

Stereospecificity for the hydrogen transfer of pyridoxal enzyme reactions.

We have studied the stereospecificities of various pyridoxal 5'-phosphate dependent enzymes for the hydrogen transfer between the C-4' of a bound coenzyme and the C-2 of a substrate in the transamination catalyzed by the enzymes. Prior to our studies, pyridoxal enzymes so far studied were reported to catalyze the hydrogen transfer only on the si-face of the planar imine intermediate formed from substrate and coenzyme. This finding had been considered as the evidence that pyridoxal enzymes have evolved divergently from a common ancestral protein, because identity in the stereospecificity reflects the similarity in the active-site structure, in particular in the geometrical relationship between the coenzyme and the active site base participating in the hydrogen transfer. However, we found that D-amino acid aminotransferase, branched-chain L-amino acid aminotransferase, and 4-amino-4-deoxychorismate lyase catalyze the re-face specific hydrogen transfer, and that amino acid racemases catalyze the nonstereospecific hydrogen transfer. These findings suggest the convergent evolution of pyridoxal enzymes. Crystallographical studies have shown that the stereospecificity reflects the active-site structure of the enzymes, and that the enzymes with the same fold exhibit the same stereospecificity. The active site structure with the catalytic base being situated on the specific face of the cofactor has been conserved during the evolution among the pyridoxal enzymes of the same family.

Binding Sites↗