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Biomedical subjects

S Takemura

Publications and source records attributed to S Takemura.

At least 19 recordsLinked to original sources
PubMed1998

A father and son with Turcot's syndrome: evidence for autosomal dominant inheritance: report of two cases.

Typical Turcot's syndrome is characterized by the association of a brain glioma together with multiple colonic polyposis, in which the number of polypoid lesions is small and the association of colonic cancer occurs at a younger age than in familial adenomatous polyposis. We describe a family in which both the father and his son presented with typical Turcot's syndrome without parental consanguinity. This is the first report of a family that is considered to follow an autosomal dominant inheritance. After reviewing 25 documented cases in which the average age of death was 20.3 years old, it was learned that the major cause of death was brain tumor (76 percent) and the minor cause was colon cancer (16 percent). Patients were very young and, therefore, unlikely to have produced a child before their death. These facts seem to support the theory that Turcot's syndrome is an autosomal dominant disorder.

Adenomatous Polyposis Coli↗
PubMed1998

Role of nitric oxide in extracellular nucleotide-induced contractile status of assorted vessels including parts of the portal vasculature.

BACKGROUND/AIMS: The resistance of portal vein and hepatic artery plays an important role in the regulation of the circulatory status in the liver, but the regulatory mechanisms for these hepatic vessels have still to be elucidated. The aim of this study was to discover the tonus regulation of the hepatic vasculature. METHODS: The effects of adenosine, adenosine 5'-monophosphate, adenosine 5'-diphosphate, adenosine 5'-triphosphate and uridine triphosphate on the force generation of the portal vein, superior mesenteric artery, inferior caval vein and aorta of the rat were studied in vitro. Each vessel was removed and cut into 5-mm ring strips. The strips were fixed vertically between triangle hooks and incubated in organ baths containing Krebs-Henseleit solution. The change in vascular tension was continuously monitored by a force-displacement transducer and recorded isometrically with a polygraph. RESULTS: Adenosine 5'-diphosphate and adenosine 5'-triphosphate induced relaxation of superior mesenteric artery and aorta precontracted with prostaglandin F2alpha dose-dependently. The effects of adenosine 5'-diphosphate and adenosine 5'-triphosphate were attenuated in the presence of N(G)-nitro-L-arginine, indicating nitric oxide dependency. In contrast, all these nucleotides dose-dependently induced contraction of the portal vein obtained from the hepatic hilus. N(G)-nitro-L-arginine decreased the EC50 values for these metabolites. Interestingly, all the nucleotides failed to induce contraction of the inferior caval vein and the portal vein distal to the hepatic hilus. CONCLUSIONS: These results suggest that some purinoceptor-dependent pathway regulates contraction of the portal vein close to the hepatic hilus and elicits, in contrast, the relaxation of superior mesenteric artery and aorta. Nitric oxide may participate in the tonus regulation of hepatic vasculature.

Animals↗
PubMed1998

Simultaneous HLA Class I and Class II antibodies screening with flow cytometry.

A flow cytometric method of simultaneously screening both HLA Class I and Class II panel reactive antibodies (PRA) was developed using a pool of 30 different Class I and 30 different Class II microbeads coated with purified HLA antigens. The antibodies in the serum that react specifically to the coated HLA antigens are detected by using a FITC-conjugated antibody against human IgG. Percent PRA can be determined by the percentage of microbeads that react positively to the serum. There is no cross-reactivity between the Class I and Class II microbeads. A mixture of Class I and Class II microbeads can be distinguished by their different fluorescent properties on the flow cytometry analysis. Thus, both Class I and Class II PRA can be detected from a single tube reaction.

Antibodies↗
PubMed1997

Effect of thiol status on nitric oxide metabolism in the circulation.

To elucidate the dynamics of nitric oxide (NO) metabolism in the circulation and its relationship with glutathione metabolism, formation of nitrosylhemoglobin (NO-Hb), S-nitrosothiols (RSNO), and nitrite+nitrate (NOx) was determined in blood samples from normal rats and animals that were treated with a loading dose of GSH or L-buthionine-[S,R]-sulfoximine (BSO), a specific inhibitor of GSH synthesis. When incubated in vitro with 0.2 mM NOC7, an NO donor, NO-Hb levels increased rapidly, peaked at 10 min, and decreased thereafter with a half-life of 35 min in blood samples from control, BSO-treated, or GSH-loaded animals. Levels of low-molecular-weight RSNO in plasma samples from the three animal groups also increased transiently, peaked at 10 min, and decreased thereafter. However, the amount of RSNO formed in GSH-loaded rat plasma was significantly greater than in control and BSO-treated animals. Plasma levels of NOx rapidly and similarly increased in all animal groups. Intravenously injected NOC7 also generated NO-Hb in circulating erythrocytes. In control animals, blood levels of NO-Hb increased maximally at 30 min and decreased thereafter with a half-life of 100 min. NO-Hb formed in the GSH-loaded group was significantly lower than in the control group. In contrast, the rate of NO-Hb formation was significantly higher with the BSO-treated group than with the control group. Although NOC7 did not affect the plasma levels of low-molecular-weight RSNO in plasma of both control and BSO-treated groups, it significantly increased RSNO in the GSH-loaded group. Thirty minutes after administration of NOC7, about 20% of the dose was recovered as plasma NOx in all animal groups. These results suggested that GSH status in animals might affect the metabolism of NO.

Animals↗
PubMed1997

Physicochemical and disposition characteristics of antisense oligonucleotides complexed with glycosylated poly(L-lysine).

The disposition characteristics of a 20 mer antisense phosphodiester oligonucleotide (PO) and its fully phosphorothioated derivative (PS) alone or complexed with glycosylated poly(L-lysine) (galactosylated polylysine, Gal-PLL; mannosylated polylysine, Man-PLL) were studied in mice in relation to their physicochemical characteristics. Good complex formation was obtained at a ratio of 1:0.6, w/w [oligonucleotides (ODNs)/carrier]. The 1:0.6 weight ratio of ODNs/Gal-PLL and ODNs/Man-PLL complexes had zeta potentials of -27 to -31 mV and mean particle size of 100 to 160 nm. After intravenous injection, 35S-labeled ODNs were eliminated rapidly from the circulation; however, their organ disposition characteristics depended on their type. Complex formation with glycosylated PLL increased the hepatic uptake and decreased the urinary clearance of these ODNs to a great extent. These complexes were taken up by both liver parenchymal cells (PC) and nonparenchymal cells (NPC). However, ODNs/Gal-PLL complexes showed a fairly high PC concentration, whereas ODNs/Man-PLL complexes distributed equally to both PC and NPC. The hepatic uptakes of PS/Gal-PLL and PS/Man-PLL complexes were partially inhibited by prior administration of Gal-BSA and Man-BSA, respectively, suggesting their hepatic uptake via the respective receptor-mediated endocytosis. However, uptake by galactose receptors of Kupffer cells, zeta potential, particle size, and Kupffer cell phagocytosis also seem to influence their uptake process. In conclusion, this study illustrates that ODNs can be delivered to hepatocytes and macrophages via galactose and mannose receptors, respectively.

Animals↗
PubMed1997

[Relationship between HLA-DRB1 genotypes and efficacy of oral type II collagen treatment using chicken cartilage soup in rheumatoid arthritis].

The correlation between the efficacy of type II collagen (C II) treatment of the rheumatoid arthritis (RA) and the existence of HLA-DRB 1 * 0405 allele was investigated in two groups of patients; the first group had HLA-DRB 1 * 0405 allele (the 0405 group) and the second had no such allele (the non-0405 group). Thirty-eight RA patients were given a chicken cartilage soup containing heat degenerated C II (the CII group) or a placebo soup (the placebo group) for three months. The 38 cases were composed of 11 cases in the 0405/C II group, 9 in the 0405/placebo group, 11 in the non-0405/C II group, 9 cases in the non-0405/placebo group. In the C II group, there was a significant increase in the anti-human C II IgA antibody serum titers (p = 0.003) and significant decrease in the anti-human C II IgG titer (p < 0.0001). The differences in the number of swollen and tender joints were statistically significant between the 045/C II and 0405/placebo groups (p of the swollen joints = 0.03, and p of the tender joints = 0.03), and between the 0405/C II and non-0405/C II groups (p = 0.006 and 0.01, respectively). We concluded that oral C II could have a therapeutic efficacy in RA patients with HLA-DRB 1 * 0405 allele.

Administration, Oral↗
PubMed1997

[Relationship between medical services utilization and preventive health behavior].

The purpose of this study was to examine the relationship between medical services utilization and preventive health behavior and to seek the factors affecting them. Subjects were 568 persons who were from 40 to 59 years old and lived in a community. Preventive health behaviors they actually performed and their interests in health were asked by questionnaire. Preventive health behaviors assessed included smoking behavior, drinking behavior, adequate hours of sleep, physical exercise, regularity of meals, and medical checkups. Medical services utilization, which included the number of visits to medical care providers, was measured by their medical claims during one year. Except for adequate hours of sleep, preventive health behaviors correlated positively with each other. A strong positive correlation was found between medical services utilization and medical checkups. However, correlations between medical services utilization and other preventive health behaviors were not statistically significant. Persons who performed preventive health behaviors and persons who utilized medical services scored higher in interest in health than persons who didn't. These results show that medical services utilization and preventive health behavior are strongly associated with interest in health, but are weakly correlated with each other.

Adult↗
PubMed1997

[Costs of health services for the elderly and related factors in cities of Japan].

OBJECTIVES: To estimate the costs of health services for the elderly in 1994 and to examine factors affecting them. METHODS: Questionnaires were sent to 631 cities and responses from 339 cities were received. Data obtained from questionnaires were total cost, proportion of labor sent to total cost, cost per user, cost per person eligible to receive Health services for the elderly. These variables were measured for health counseling service, health education, health examinations, functional training, and home-visit guidance. RESULTS: The proportion of labor cost was smaller for health examinations than for other services. Health examinations and home-visit guidance showed higher correlation coefficients between the number of users and the total cost than other services. In most services, cost per eligible person were negatively correlated with the number of residents in the city and positively correlated with the number of public health nurses per resident. However, costs per user did not show a correlation. The cities which established municipal health centers had lower costs per user of health education and functional training than the cities which did not. Standardized mortality ratios of cerebrovascular disease and stomach cancer were not correlated with total cost, proportion of labor cost, cost per user, cost per eligible person in most services. CONCLUSIONS: For the economic evaluation of health services for the elderly, it is necessary to examine the relationship between cost, both quantity and quality, and effectiveness of health services.

Aged↗
PubMed1997

Irreversible inhibition of cytochrome P450 by nitric oxide.

Nitric oxide (NO) modulates various metabolisms through interaction with thiol proteins and hemoproteins. Although NO interacts reversibly with iron moieties of heme proteins, including cytochrome P450 (P450), dynamic aspects of the formation, catalytic functions and fates of NO-P450 adducts remain to be elucidated. When incubated with NOC7, which spontaneously and stoichiometrically releases NO within 5 min, microsomal P450 rapidly formed nitrosyl-heme adducts as determined by the electron spin resonance method. The signal intensity for the complex increased with time, peaking at 30 min and decreasing to below detectable levels by 60 min of incubation. In contrast, the microsomal levels of low-spin ferric forms of P450 (g = 2.26) rapidly decreased during the initial 30 min but recovered time-dependently thereafter. Analysis by differential spectra (reduced form/CO-reduced form) revealed that on incubation with NOC7, the form of microsomal P450 also changed in a biphasic manner. To elucidate the mechanism for the decrease in the levels of P450, microsomal levels of P450 isozymes (CYPs) were determined by Western blot analysis using specific antibodies against CYP3A2 and CYP2C11, major isoforms found in male rat liver. Kinetic analysis revealed that no appreciable degradation of P450 proteins occurred during the incubation of microsomes with NOC7. The effect of NO on the catalytic activity of the enzymes was determined by using testosterone as substrate because hydroxylation of steroid hormones is one of the major functions of P450. When exposed to NO, the hydroxylation activity in microsomes rapidly decreased during the initial 10 min and then disappeared slowly. These results suggested that NO formed dissociable complexes with P450 isozymes and the catalytic functions of these isozymes were irreversibly inactivated after dissociation from their heme moiety.

Animals↗
PubMed1997

Relationship between duration of rheumatoid arthritis before knee joint surgery and HLA-DRB1 alleles: a retrospective study.

OBJECTIVE: To examine whether genetically determined factors can be used as predictors of requirement for knee joint surgery in the early phase of rheumatoid arthritis (RA). METHODS: We determined HLA-DRB1 alleles in 322 patients with seropositive RA by polymerase chain reaction and allele specific oligonucleotide probe techniques. Patients were classified into 3 groups (S/S, S/N, and N/N) based on their possession of two, one or no susceptibility alleles of RA, respectively. The stage of radiographic change in the knee joint determined using Larsen's standard film was compared to results of genotyping. Duration of RA before joint surgery in the 3 groups was also compared retrospectively. RESULTS: The median number of years to develop to stages I, II, III, and IV and the number of years of disease duration before total knee arthroplasty (TKA) were significantly shorter in the S/S group than in the S/N and N/N groups (p < 0.05). CONCLUSION: TKA was required earlier in the S/S group than in the S/N and N/N groups. This finding will affect planning of surgical management for RA based on anticipated courses.

Adult↗
PubMed1997

[Small increase of CR1 and CR3 by C5a-receptors on polymorphonuclear leukocytes in systemic lupus erythematosus].

One of the anaphylatoxins, C5a, is known to increase the expression of the complement receptors, CR1 and CR3, on PMNs which play important roles in the phagocytosis. We measured the expression of these receptors before and after the stimulation with C5a and C5a-receptors (C5aR) on PMNs in patients with systemic lupus erythematosus (SLE). PMNs from 16 patients and 11 normal controls were tested. All the patients with SLE were administered with prednisolone orally and were in the inactive stage. The CR1 expression in SLE was significantly weak (p < 0.01) before and after stimulation with 4.55 nM (50 micrograms/ml) of C5a. There was no significant difference of CR3 expression before stimulation. However, after the stimulation with C5a, the increase of CR3 on PMNs from SLE was significantly small (p < 0.01). C5aR on PMNs showed no difference between the two groups. However, the expression of C5aR was significantly suppressed in patients treated with a high dosage of prednisolone (> = 10 mg/day) compared to those with a low dosage of prednisolone (< 10 mg/day). There was no significant difference of CR1 and CR3 expression between these groups. It is concluded that the increase of CR1 and CR3 on PMNs by C5a in small in SLE, of which impaired increase is not due to C5aR on PMNs, and that the expression of C5aR is suppressed by prednisolone.

Antigens, CD↗
PubMed1996

Albumin is an important vascular tonus regulator as a reservoir of nitric oxide.

Plasma albumin reacts with nitric oxide (NO) to form S-nitroso-albumin (albumin-S-NO). The present study was designed to elucidate whether NO-induced response on blood pressure may differ between analbuminemic rats (NAR) and normal rats. When NOC7, a NO donor, was intravenously injected in rats, blood pressure decreased and the initial depressor response was the same in both the NAR and the normal rats. However, the duration of NO-induced hypotension was 0.5 times longer in NAR than in the normal rat. After NOC7 injection, plasma thiol levels decreased and S-nitrosothiols levels increased in the normal rats, whereas these levels slightly changed in NAR. These results suggested that NO reacts with albumin-SH, resulting in albumin-S-NO formation, which produces a continuous hypotensive response in blood pressure as a slow releaser of NO.

Animals↗
PubMed1996

Increased numbers of macrophages in noninflamed gastroduodenal mucosa of patients with Crohn's disease.

We investigated immunostained macrophages in the noninflamed mucosa of Crohn's disease patients. Biopsied specimens from endoscopically normal gastroduodenal mucosa of Crohn's disease, ulcerative colitis, and healthy control patients were studied. Sections were examined immunohistochemically using a monoclonal antibody specific for tissue macrophages (CD68). Immunostained mucosal macrophages in the second part of the duodenum, duodenal bulb, gastric antrum, and gastric body of the Crohn's disease group were more numerous than in the ulcerative colitis and control groups. The characteristic findings of Crohn's disease were aggregations, focal subepithelial dense accumulations, and infiltration throughout the mucosa of macrophages not accompanied by a lymphoid infiltrate. The number of macrophages in the gastroduodenal mucosa bore no relationship with the duration of symptoms, clinical activity, or affected site in the intestine. This suggests that the increased number of macrophages in noninflamed mucosa is a histological change characteristic for Crohn's disease that indicates a persistent latent abnormality involving the entire gastrointestinal tract.

Adolescent↗
PubMed1996

Dynamic aspects of glutathione and nitric oxide metabolism in endotoxemic rats.

Glutathione is one of the most abundant thiols in mammalian tissues and plays important roles in the defense mechanism and detoxification of various metabolites, such as reactive xenobiotics and free radicals. Nitric oxide (NO) readily reacts with thiol compounds, thereby generating chemically stable S-nitrosothiols. Although endotoxin has been known to induce NO synthase in various organs, particularly liver and spleen, and enhances the production of NO, correlation between NO and glutathione metabolism in endotoxemic subjects remains to be elucidated. The present work examines the changes in NO and glutathione metabolism in endotoxemic rats. Administration of lipopolysaccharide (LPS) markedly decreased the glutathione levels in plasma and bile, whereas it decreased the hepatic level only slightly. NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, inhibited the LPS-induced decrease of glutathione in plasma and bile. Administration of LPS increased the biliary levels of gamma-glutamyl transpeptidase (gamma-GTP) without affecting its thiol levels. Acivicin, a gamma-GTP inhibitor, inhibited the LPS-induced decrease of glutathione in plasma and bile without affecting its hepatic levels. Analysis with the use of L-buthionine sulfoximine revealed that the turnover of hepatic glutathione significantly increased in LPS-treated rats by some L-NNA-inhibitable mechanism. These results suggest that endotoxin might enhance the NO production in the liver and other tissues and significantly modulate the interorgan metabolism of reduced glutathione.

Animals↗
PubMed1996

[Demonstration and characterization of CD 46, membrane cofactor protein, in gastric cancer tissue].

CD 46, membrane cofactor protein, is a membrane protein which shows different expression and phenotypes with the organ or cell in the same individual. Previously, we reported that gastric CD 46 was expressed strongly in the mucosal epithelium, mucosa and endothelial cells of vessels in the submucosal layer. Western blot analysis revealed that gastric CD 46 was expressed as one broad band with a molecular weight ranging from 60 kDa to 69 kDa, which was different from that of lymphocytes. In this study, we investigated the differences in expression and characterization of CD 46 in gastric cancer obtained by surgery as compared with non-cancerous mucosa. Expression of CD 46 was greater in gastric cancer than in non-cancerous mucosa. In some cases, the phenotypes of CD 46 in gastric cancer were different from those in the non-cancerous tissue.

Aged↗
PubMed1996

[Expression and characterization of CD46, membrane cofactor protein, in human colonic mucosa].

CD 46, membrane cofactor protein (MCP), is a membrane regulatory glycoprotein of the complement system, and acts as a cofactor of factor I, which inactivates C3b and C4b bound on autologous cell membrane. MCP is present on human peripheral blood cells except erythrocytes, fibroblasts, epithelial and endothelial cells, and has been proved to exist in other organs including gastrointestinal tract recently. In this study the expression and characterization of MCP on normal human colonic mucosa was investigated. Immunohistochemical study showed MCP in the colonic mucosal epithelium. Western blot analysis revealed that MCP protein was expressed as a broad band of 50-65 kDa in all cases and another faint band of 43-46 kDa in 3 out of 20 cases, though the latter band was highly suspected to be originated from contaminated mononuclear cells in the colon.

Antigens, CD↗
PubMed1996

[Demonstration and characterization of CD46, membrane cofactor protein in the stomach].

CD46, membrane cofactor protein, is a glycoprotein widely present on the cell membranes and is different in molecular weight among organs or cells in the same individual. It acts as a cofactor of I of the complement system, which inactivates C3b bound to the autologous cells, and protects them from the attack of the complement. In this study CD46 was demonstrated in the stomach immunochemically. Gastric CD46 was expressed strongly in the mucosal epithelium, mucosa and endothelial cells of the vessels in the submucosal layer, whereas expressed weakly in the submucosa and muscle. Western blot analyses revealed that gastric CD46 was expressed as one broad band with molecular weight ranging from 60 kDa to 69 kDa, which was distinct from that of lymphocytes in the peripheral blood.

Aged↗