[Guidelines on Treatment of Hypertension in the Elderly--2002 Revised Version].
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Biomedical subjects
Publications and source records attributed to K Shimada.
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In order to establish an appropriate treatment for thymic carcinoma, clinical courses of 15 patients with type C thymoma of WHO classification were reviewed. Five-years survival rate in all patients was 37.6%. In cases underwent complete resection, survival was 48.5%. The induction chemotherapy was done in 7 cases, and complete resection was possible in all these cases, suggested the possibility of improving the survival by the induction therapy. Upper mediastinal lymph node dissection each performed in 9 cases, and they showed significantly better survival than those without lymph node dissection. In conclusion, we have found that induction chemoradiotherapy and complete tumor resection with lymphnode dissection would contribute to improvement of the results in treatment for thymic carcinoma.
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Little is known about the dynamics of chromosomes in interphase nuclei. By tagging four chromosomal regions with a green fluorescent protein fusion to lac repressor, we monitored the movement and subnuclear position of specific sites in the yeast genome, sampling at short time intervals. We found that early and late origins of replication are highly mobile in G1 phase, frequently moving at or faster than 0.5 micrometers/10 seconds, in an energy-dependent fashion. The rapid diffusive movement of chromatin detected in G1 becomes constrained in S phase through a mechanism dependent on active DNA replication. In contrast, telomeres and centromeres provide replication-independent constraint on chromatin movement in both G1 and S phases.
This review article underlines the importance of gas chromatography (GC), high-performance liquid chromatography (HPLC) and their hyphenated techniques using mass spectrometry (MS) for the determination of natural steroids, especially in human biological fluids. Steroids are divided into eight categories based on their structures and functions, and recent references using the above methodologies for the analysis of these steroids are cited. GC and GC-MS are commonly used for the determination of volatile steroids. Although HPLC is a widely used analytical method for the determination of steroids including the conjugated type in biological fluids, LC-MS is considered to be the most promising one for this purpose because of its sensitivity, specificity and versatility.
BACKGROUND: The objective of this study was to analyze the clinicopathologic variables and the postoperative outcome in patients with mass-forming intrahepatic cholangiocarcinoma (ICC) to identify important factors for predicting postresection prognosis. Although it has been reported that mass-forming ICC has a different etiology and biologic features compared with hepatocellular carcinoma (HCC), patients with ICC have been dealt with clinicopathologically in the same manner as patients with HCC. METHODS: Sixty patients who underwent hepatectomy for mass-forming ICC with curative intent between 1981 and 1999 were studied. Fourteen preoperative clinical and diagnostic parameters and 12 postoperative surgicopathologic parameters were analyzed. RESULTS: The rate of operative mortality in this patient cohort was 5%, and the overall 1-year, 3-year, and 5-year survival rates were 68%, 35%, and 29%, respectively, with a median survival of 19.6 months. A multivariate analysis revealed that independent negative prognostic factors were 1) hepatic regional lymph node metastasis, 2) multiple tumor presentation, 3) symptomatic tumor, and 4) the presence of vascular invasion. Using these factors, a new staging system was devised: Stage I disease was defined as a solitary tumor without vascular invasion, Stage II disease was defined as a solitary tumor with vascular invasion, Stage IIIA disease was defined as multiple tumors with or without vascular invasion, Stage IIIB disease was defined as any tumor with regional lymph node metastasis, and Stage IV disease was defined as any tumor with distant metastases. The Kaplan-Meier estimated 3-year survival rate and the median survival for each subgroup were 74% for patients with Stage I disease (median survival is the time when the cumulative survival rate of some patients' group declined to 50%; thus, the median survival could not be calculated in patients with Stage I disease because survival was 74% at the latest follow-up), 48% and 26.2 months for patients with Stage II disease, 18% and 16.8 months for patients with Stage IIIA disease, and 7% and 11.2 months for patients with Stage IIIB disease, respectively (P < 0.0001). None of the patients met the criteria for Stage IV disease. CONCLUSIONS: The current results support the use of a new staging system for patients with ICC that is simple and predicts well the differences in survival after patients undergo hepatic resection.
[structure: see text]. A stable selenenic acid was synthesized by direct oxidation of a selenol bearing a novel bowl-type substituent with H2O2, and its structure was established by X-ray crystallographic analysis. Selenenyl sulfides obtained by the reaction of the selenenic acid with 1,4-dithiols were reduced to the corresponding selenol by treatment with a tertiary amine, thus achieving the experimental demonstration of three processes included in the catalytic cycle of glutathione peroxidase.
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BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. PPARgamma mRNA is present in cardiac myocytes; however, whether PPARgamma affects cardiac hypertrophy remains unknown. METHODS AND RESULTS: We investigated the effects of PPARgamma activators on cardiac hypertrophy in neonatal rat cardiac myocytes. Cyclic 4% biaxial mechanical strain caused enlargement of cardiac myocytes (1.3-fold versus control, P<0.0001), but the PPARgamma activators troglitazone and 15-deoxy-Delta(12-14)-prostaglandin J(2) (15d-PGJ(2)) (10 micromol/L) inhibited this effect (troglitazone, -72%, P<0.0005; 15d-PGJ(2), -88%, P<0.0002). Total cell protein was increased by mechanical strain (control, 164.3 microgram/dish; strain, 265.5, P<0.0002), and this effect was inhibited by troglitazone and 15d-PGJ(2) (troglitazone, -61%, P<0.005; 15d-PGJ(2), -72%, P<0.001). [(3)H]Leucine uptake was also increased by mechanical strain (1.9-fold versus control, P<0.002), and this increase was inhibited by troglitazone and 15d-PGJ(2) (troglitazone, -52% at 10 micromol/L, P<0.01; 15d-PGJ(2), -70% at 10 micromol/L, P<0.005). An increase in [(3)H]leucine uptake induced by angiotensin II or phenylephrine was significantly inhibited by troglitazone and 15d-PGJ(2). Mechanical strain induced mRNA expression for brain natriuretic peptide, but PPARgamma activators inhibited this induction. Furthermore, PPARgamma activators inhibited mechanically induced activation of nuclear factor (NF)-kappaB. Pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB activation, inhibited strain-induced [(3)H]leucine uptake (-50% at 100 micromol/L, P<0.05). CONCLUSIONS: These results demonstrate that PPARgamma activators inhibit cardiac hypertrophy in cardiac myocytes and suggest that PPARgamma activators may regulate cardiomyocyte hypertrophy at least partially through the NF-kappaB pathway.
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BACKGROUND: Blood pressure increases transiently after a major earthquake, but the characteristics and the mechanism of this increase are unknown. METHODS: The study involved 124 elderly hypertensive outpatients from two clinics near the epicenter of the Hanshin-Awaji earthquake (7.2 on the Richter scale) for whom ambulatory blood pressure monitoring and assessment of end-organ damage had been performed before the earthquake. RESULTS: During the 1 to 2 weeks after the earthquake, while major aftershocks persisted, mean (+/- SD) systolic blood pressure was 14 +/- 16 mm Hg greater and mean diastolic blood pressure was 6 +/- 10 mm Hg greater, but these values returned to baseline by 3 to 5 weeks after the earthquake. The earthquake-induced increase in blood pressure correlated significantly with the "white coat" effect ([clinic systolic blood pressure minus 24-hour systolic blood pressure] r = 0.34, P <0.001), body mass index (r = 0.28, P <0.001), and age (r = 0.24, P <0.01). The earthquake-induced blood pressure increase was prolonged in patients with microalbuminuria for at least 2 months after the earthquake, whereas it was less pronounced in patients who had been treated with an alpha-blocker and in patients with diabetes mellitus. CONCLUSIONS: These elderly patients with hypertension had a substantial increase in blood pressure after a major earthquake; the increase was usually transient, except in patients who had microalbuminuria. The correlation with white-coat hypertension suggests that both phenomena are related to sympathetic activation.
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To elucidate the role of p53/p16(INK4a)/RB1 pathways in the tumorigenesis of primary central nervous system lymphomas (PCNSLs), we have analyzed p14(ARF), p16(INK4a), RB1, p21(Waf1), and p27(Kip1) status in a series of their 18 sporadic cases of diffuse large B-cell lymphoma, using methylation-specific PCR, differential PCR, and immunohistochemistry. Homozygous deletion or methylation of p14(ARF) was detected in 10 (56%) PCNSLs, and they were almost entirely deletions (except 1 case). A total of 11 (61%) PCNSLs demonstrated homozygous deletion (6 cases) or methylation (5 cases) of p16(INK4a). Six tumors showed both p14(ARF) and p16(INK4a) homozygous deletions. Hypermethylation of the RB1 and the p27(Kip1) promoter region was detected in 2 (11%) cases, whereas p21(Waf1) methylation was not detected in any. Immunohistochemistry revealed loss of p14(ARF) and p16(INK4a) expression in 10 (56%) samples, correlating with the gene status. Four cases showed independent negative immunoreactivity for pRB and p27(Kip1), and nearly one-half of cases (8 of 18; 44%) were characterized by lack of p21(Waf1) expression. These results indicate that inactivation of p14(ARF) and p16(INK4a) by either homozygous deletion or promoter hypermethylation represents an important molecular pathogenesis in PCNSLs. Hypermethylation of RB1, p21(Waf1), and p27(Kip1) appears to be of minor significance, these genes being independently methylated in PCNSLs.
The cytochrome subunit bound to the photosynthetic reaction center (RC) complex in Rhodovulum sulfidophilum lacks one heme-binding motif (CXXCH) out of four motifs found in other purple bacteria resulting in the absence of the most distal heme from the RC-core complex (S. Masuda et al., J. Biol. Chem. 274 (1999) 10795). Cytochrome c(2), which acts as the electron donor to the RC was purified, and its gene was cloned and sequenced. The redox midpoint potential of cytochrome c(2) was determined to be E(m)=357 mV. The photo-oxidation and re-reduction of purified cytochrome c(2) were observed in the presence of membrane preparations. Flash-induced photo-oxidation and re-reduction of the RC-bound cytochrome were also observed in intact cells. Despite the unusual nature of the RC-bound cytochrome subunit, the cyclic electron transfer system in Rdv. sulfidophilum was shown to be similar to those in other purple bacteria.
The tetraheme cytochrome subunits of the photosynthetic reaction centers (RCs) in two species of purple bacteria, Rubrivivax gelatinosus and Blastochloris (Rhodopseudomonas) viridis, were compared in terms of their capabilities to bind different electron-donor proteins. The wild-type RCs from both species and mutated forms of R. gelatinosus RCs (with amino acid substitutions introduced to the binding domain for electron-donor proteins) were tested for their reactivity with soluble cytochromes and high potential iron-sulfur protein. Cytochromes from both species were good electron donors to the B. viridis RC and the R. gelatinosus RC. The reactivity in the R. gelatinosus RC showed a clear dependence on the polarity of the charges introduced to the binding domain, indicating the importance of the electrostatic interactions. In contrast, high potential iron-sulfur protein, presumed to operate according to the hydrophobic mechanism of binding, reacted significantly only with the R. gelatinosus RC. Evolutionary substitution of amino acids in a region of the binding domain on the cytochrome subunit surface probably caused the change in the principal mode of protein-protein interactions in the electron-transfer chains.
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OBJECTIVES: We sought to study the association of the silent cerebral infarct (SCI), a predisposing condition of stroke, with hyperinsulinemia and hemostatic abnormalities in older hypertensive subjects. BACKGROUND: Hypertension is a powerful risk factor for stroke. However, the role of other risk factors for stroke in hypertensive subjects remains incompletely understood. METHODS: We performed brain magnetic resonance imaging and measured cardiovascular risk factors, by administering the 75-g oral glucose tolerance test and measuring plasma insulin and hemostatic variables, in 123 asymptomatic hypertensive subjects (mean age 69 years). RESULTS: At least one SCI was detected in 80 subjects (65%), and multiple SCIs were found in 48 subjects (39%). The presence of SCIs was associated with older age, higher levels of 24-h systolic blood pressure, 2-h insulin, thrombin-generation markers (prothrombin fragment 1+2 and thrombin-antithrombin complexes), plasminogen activator inhibitor-1 (PAI-1), D-dimer and von Willebrand factor (vWF), but not with plasmin-alpha2-plasmin complex (PIC) levels. The 2-h insulin area under the curve (AUC) was positively correlated with PAI-1 and vWF levels (p < 0.01), and the PAI-1 level was negatively correlated with the PIC level (p < 0.02). Multiple logistic regression analysis revealed that age and the 2-h insulin AUC were significantly associated with SCIs, particularly those located in the subcortical white matter, and hemostatic abnormalities were significantly associated with the presence of multiple SCIs, particularly those located in the basal ganglia. CONCLUSIONS: In older asymptomatic hypertensive subjects, hyperinsulinemia appears to be associated with lacunar-type SCIs, particularly those located in the subcortical white matter, and hemostatic abnormalities show an association with the presence of multiple SCIs, particularly those located in the basal ganglia.