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Biomedical subjects

Y Nagata

Publications and source records attributed to Y Nagata.

At least 127 records · Page 7Linked to original sources

[Social psychological factors of interest in lay personality theories: why is ABO blood-typing popular?].

We hypothesized that one of the reasons that not a few Japanese are interested in lay personality theories of ABO blood-typing and similar unsupported beliefs on human nature, was unsatisfied needs of having clear collective and personal identities. To test the hypothesis, we asked 149 married women, 34 to 62 years of age, to describe themselves as in self introduction to strangers, and then separately indicate the degree of interest in lay personality theories. We then counted the number of references to personal/private aspects (an index of personal identity) and the number to social groups whose membership was known to be exclusive and limited (an index of collective one). Results showed that those who were high on both indices were less interested in lay theories than those low on one or both of personal and collective indices.

ABO Blood-Group System↗

Structures of ADP-ribosylated rifampicin and its metabolite: intermediates of rifampicin-ribosylation by Mycobacterium smegmatis DSM43756.

23-(O-ADP-Ribosyl)rifampicin [RIP-TAs (3, Na+ form), RIP-TAf (4, H+ form)] was obtained as an intermediate in the conversion process of rifampicin (1) to RIP-Mb (2) that is mediated by cell homogenates of Mycobacterium smegmatis DSM43756 or of Escherichia coli carrying a mycobacterial mono(ADP-ribosyl) transferase gene, in the presence of NADH. 23-[O-(5'-Phosphoribosyl)]rifampicin (5, RIP-TAp) was also obtained by the reaction of rifampicin with NADH in the presence of a homogenate of M. smegmatis. The structures of 3, 4, and 5 were determined by means of MS and NMR analyses.

ADP Ribose Transferases↗

[Catastrophic pulmonary vasoconstriction associated with protamine reversal of heparin].

Administration of protamine intravenously to neutralize the anticoagulant effects of heparin may be associated with hypotension. These adverse cardiovascular responses to protamine fall into three distinct types: transient hypotension related to rapid drug administration; anaphylactic responses: and catastrophic pulmonary vasoconstriction. We recently observed three patients who had catastrophic pulmonary vasoconstriction, which were treated with the assist circulation and intraaortic balloon pumping. The two patients were survived except one who was dead due to the cerebral ischemic damage which was introduced by delayed establishment of circulatory assist device. We conclude that meticulous longstanding observation of the hemodynamic condition is important after administration of protamine under the unremoved cannulations.

Aged↗

[Surgical treatment for infective endocarditis with multiple embolic complications].

A 59-year-old man was transferred to our hospital because of severe right leg pain, dyspnea and anuria. Due to severe cyanosis of the legs below the knees and severe hyperkalemia, he had undergone embolectomy of the right femoral artery and hemodialysis. Medical treatment for infective endocarditis was started after the first operation, because transesophageal echo cardiography revealed severe aortic regurgitation and massive vegetation of the aortic valve. Amputation of the right leg below the knee and of the left leg below the Lisfranc joint was performed after 19 days and aortic valve replacement with patch closure of a perivalvular abscess was performed one month after the first operation. The post-operative course was uneventful. He was weaned from hemodialysis and the follow-up echocardiographic study revealed no vegetation.

Abscess↗

Relation of estrogen receptor expression in endometrial cancer specimens to bone mineral density.

BACKGROUND: To investigate the relation of estrogen and progesterone receptor (ER and PR) expression in endometrial cancer specimens to bone mineral density (BMD). MATERIALS AND METHODS: Subjects were 48 postmenopausal women with endometrial cancer treated with hysterectomy. Baseline characteristics included age, years since menopause (YSM), height, weight, and body mass index (BMI). Lumbar spine BMD (L2-4), the ratio of trunk fat to leg fat mass (trunk-leg fat ratio), body fat mass, and the percentage of body fat were measured by dual-energy x-ray absorptiometry (DEXA). ER and PR expression in endometrial cancer specimens were determined immunohistochemically. RESULTS: Of 48 women, 32 (66.7%) were ER/PR-positive, nine (18.8%) were ER/PR-negative, three (6.3%) were ER-positive/PR-negative, and four (8.3%) were ER-negative/PR-positive. Lumbar spine BMD and trunk-leg fat ratio were significantly higher in women with ER-positive than in those with ER-negative (p<0.05), but other variables did not differ between the two groups. BMD and baseline- and anthropometric characteristics did not differ between the two groups divided by the presence or absence of PR expression. CONCLUSIONS: ER expression in endometrial cancer specimens is associated with higher lumbar spine BMD.

Aged↗

Relationships between serum leptin level and regional bone mineral density, bone metabolic markers in healthy women.

BACKGROUND: Leptin might affect bone metabolism. This study was performed to investigate the relationship of leptin to bone metabolism in detail in premenopausal and postmenopausal healthy women. METHODS: The relationships between serum leptin level and bone mineral density of several regional sites of the body as well as whole body, along with bone metabolic markers, were examined in 47 premenopausal and 29 postmenopausal healthy women. RESULTS: Serum leptin level was weakly correlated with bone mineral density of pelvis (Pearson's correlation coefficient r=0.39, p<0.05) and left leg (r=0.41, p<0.01) in the premenopausal women, although the correlation decreased after adjustment for BMI. There was no significant relationship between serum leptin level and whole body bone mineral density both in the premenopausal and postmenopausal women. Serum leptin level was correlated with serum alkaline phosphatase (r=0.56, p<0.001) and urinary deoxypyridinoline/cr (r=-0.32, p<0.05) by Pearson's correlation test in the premenopausal women; the relationships were maintained even after adjustment for BMI (r=0.50 and -0.48, respectively). CONCLUSIONS: Leptin is not a key regulator of bone metabolism, although it may have some effects on bone metabolic markers and BMD regionally in premenopausal women.

Adult↗

Complex mechanisms underlying impaired activation of Cdk4 and Cdk2 in replicative senescence: roles of p16, p21, and cyclin D1.

Numerous changes in gene expression are known to occur during replicative senescence, including changes in genes involved in the cell cycle control. In the present study, we have found a severe impairment in the activation of Cdk2 and Cdk4 in response to mitogens in senescent human fibroblasts and determined the molecular basis for this. Although Cdk4 protein was constitutively expressed in senescent cells at the same level as in early-passage young cells, it was found to be complexed with a distinct set of Cdk inhibitors. Cdk4 derived from early passage quiescent cells was effectively activated by incubation with cyclin D1 and Cdk-activating kinase (CAK) in vitro, whereas Cdk4 from senescent cells was not. Cdk2 protein was dramatically decreased in senescent cells and complexed primarily with cyclin D1 and p21. This cyclin D1-bound Cdk2 was not activated by CAK either in vivo or in vitro, implicating cyclin D1 as an inhibitor of Cdk2 activation. Thus, one of the underlying molecular events involved in replicative senescence is the impaired activation of Cdk4 and Cdk2 due to increased binding of p16 to Cdk4 and increased association of Cdk2 with cyclin D1 and p21.

Blood Proteins↗

Occurrence of D-amino acids in a few archaea and dehydrogenase activities in hyperthermophile Pyrobaculum islandicum.

The contents of D-enantiomers of serine, alanine, proline, glutamate (glutamine) and aspartate (asparagine) were examined in the membrane fractions, soluble proteins and free amino acids from some species of archaea, Pyrobaculum islandicum, Methanosarcina barkeri and Halobacterium salinarium. Around 2% (D/D+L) of D-aspartate was found in the membrane fractions. In the soluble proteins, the D-amino acid content was higher in P. islandicum than that in the other archaeal cells: the concentrations in P. islandicum were 3 and 4% for D-serine and D-aspartate, respectively. High concentrations of free D-amino acids were found in P. islandicum and H. salinarium; the concentrations of D-serine (12-13%), D-aspartate (4-7%) and D-proline (3-4%) were higher than those of D-alanine and D-glutamate. This result showed a resemblance between these archaea and not bacterial, but eukaryotic cells. The presence of D-amino acids was confirmed by their digestion with D-amino acid oxidase and D-aspartate oxidase. The occurrence of D-amino acids was also confirmed by the presence of activities catalyzing catabolism of D-amino acids in the P. islandicum homogenate, as measured by 2-oxo acid formation. The catalytic activities oxidizing D-alanine, D-aspartate and D-serine at 90 degrees C were considerably high. Under anaerobic conditions, dehydrogenase activities of the homogenate were 69, 84 and 30% of the above oxidase activities toward D-alanine, D-aspartate and D-serine, respectively. Comparable or higher dehydrogenase activities were also detected with these D-amino acids as substrate by the reduction of 2, 6-dichlorophenolindophenol. No D-amino acid oxidase activity was detected in the homogenates of M. barkeri and H. salinarium.

Amino Acids↗

The stabilization mechanism of mutant-type p53 by impaired ubiquitination: the loss of wild-type p53 function and the hsp90 association.

Mutant-type p53 (mt p53) is largely accumulated in cancer cells due to its increased stability. To elucidate the mechanism of mt p53 stabilization, we analysed the turnover of p53 mutated at codon 248 whose alteration is most frequently found in human cancers. Proteasome inhibition induced the accumulation of ubiquitinated mt p53, indicating that the ubiquitinated forms were essentially unstable and degraded by the proteasome. The presence of a small amount of the ubiquitinated mt p53 relative to the abundant non-ubiquitinated form suggested that the mt p53 ubiquitination was a rate-limiting process in the slow turnover. Two phenomena destabilizing mt p53 via the ubiquitin-proteasome degradation were proved to be independent. First, the coexpression of wild-type p53 (wt p53) promoted mt p53 destabilization as feedback regulation. Second, geldanamycin also induced mt p53 destabilization through the dissociation of the protein from hsp90 but not through the restoration of wt p53 function. Neither the mutant-specific conformation nor the N-terminal phosphorylation seemed to contribute directly to the mt p53 stabilization. Further, a two-dimensional gel electrophoresis revealed that most of the post-translationally modified mt p53 was equally subjected to ubiquitination and subsequent proteasomal degradation. These findings are evidence that mt p53 stabilization depends on the impaired ubiquitination due to both the loss of wt p53 function and the hsp90 association.

Amino Acid Sequence↗

Crystal structure of chitosanase from Bacillus circulans MH-K1 at 1.6-A resolution and its substrate recognition mechanism.

Chitosanase from Bacillus circulans MH-K1 is a 29-kDa extracellular protein composed of 259 amino acids. The crystal structure of chitosanase from B. circulans MH-K1 has been determined by multiwavelength anomalous diffraction method and refined to crystallographic R = 19.2% (R(free) = 23.5%) for the diffraction data at 1.6-A resolution collected by synchrotron radiation. The enzyme has two globular upper and lower domains, which generate the active site cleft for the substrate binding. The overall molecular folding is similar to chitosanase from Streptomyces sp. N174, although there is only 20% identity at the amino acid sequence level between both chitosanases. However, there are three regions in which the topology is remarkably different. In addition, the disulfide bridge between Cys(50) and Cys(124) joins the beta1 strand and the alpha7 helix, which is not conserved among other chitosanases. The orientation of two backbone helices, which connect the two domains, is also different and is responsible for the differences in size and shape of the active site cleft in these two chitosanases. This structural difference in the active site cleft is the reason why the enzymes specifically recognize different substrates and catalyze different types of chitosan degradation.

Amino Acid Sequence↗

PcpA, which is involved in the degradation of pentachlorophenol in Sphingomonas chlorophenolica ATCC39723, is a novel type of ring-cleavage dioxygenase.

The pentachlorophenol (PCP) mineralizing bacterium Sphingomonas chlorophenolica ATCC39723 degrades PCP via 2,6-dichlorohydroquinone (2,6-DCHQ). The pathway converting PCP to 2,6-DCHQ has been established previously; however, the pathway beyond 2,6-DCHQ is not clear, although it has been suggested that a PcpA plays a role in 2, 6-DCHQ conversion. In this study, PcpA expressed in Escherichia coli was purified to homogeneity and shown to have novel ring-cleavage dioxygenase activity in conjunction with hydroquinone derivatives, and converting 2,6-DCHQ to 2-chloromaleylacetate.

Amino Acid Sequence↗

Requirement of activation of JNK and p38 for environmental stress-induced erythroid differentiation and apoptosis and of inhibition of ERK for apoptosis.

C-Jun amino terminal kinase/stress-activated protein kinases (JNK/SAPK) and p38 subgroups of mitogen-activated protein kinases have been suggested to play a critical role in apoptosis, cell growth, and/or differentiation. We found that a short exposure of SKT6 cells, which respond to erythropoietin (Epo) and induce erythroid differentiation, to osmotic or heat shock induced transient activation of JNK/SAPK and p38 and inactivation of ERK and resulted in erythroid differentiation without Epo, whereas long exposure of the cells to these stresses induced prolonged activation/inactivation of the same kinases and caused apoptosis. Inhibition of JNK/SAPK and p38 resulted in inhibition of stress-induced erythroid differentiation and apoptosis. Inhibition of ERK had no effect on stress-induced erythroid differentiation, but stimulated apoptosis. Activation of p38 and/or JNK/SAPK for a short time caused erythroid differentiation without Epo, although its prolonged activation induced apoptosis. Activation of ERK suppressed stress-induced apoptosis. These results indicate that short cellular stresses, inducing transient activation of JNK/SAPK and p38, lead to cell differentiation rather than apoptosis. Furthermore, activation of JNK/SAPK and p38 is required for both cell differentiation and apoptosis, and the duration of their activation may determine the cell fate, cell differentiation, and apoptosis. In contrast, inactivation of ERK is required for stress-induced apoptosis but not cell differentiation.

Animals↗

External beam radiation therapy with or without high-dose-rate intraluminal brachytherapy for patients with superficial esophageal carcinoma.

BACKGROUND: Clinical results of external beam radiation therapy (RT) with or without intraluminal brachytherapy (IBT) for patients with superficial esophageal carcinoma were evaluated retrospectively. METHODS: Between 1985 and 1996, 21 patients with superficial esophageal squamous cell carcinoma were treated by external beam RT, with or without high dose rate IBT, with curative intent. There were 18 males and 3 females; their median age was 67 years (range, 51-85 years). Eight patients were treated by external beam RT alone (60-69 gray [Gy]), whereas the remaining 13 patients were treated by IBT after external beam RT. Most patients in the IBT group received 2 or 3 fractions of IBT of 4 Gy after external beam RT of 50-56 Gy. RESULTS: All of the 21 tumors showed complete regression at the end of RT. Local recurrence was noted in 4 patients in the group that received external beam RT alone and in 2 patients in the IBT group. Salvage therapy was successful for 4 patients. Local control probability and cause specific survival probability for the IBT group were significantly higher than those for the group that received external beam RT alone (P < 0.05 for both). The 3-year local control and cause specific survival rates for the IBT group were 85% and 100%, respectively, whereas those for the external beam RT group were 45% and 67%, respectively. Transient esophageal ulcers were noted in two patients in the IBT group. CONCLUSIONS: External beam RT and IBT is a safe and effective treatment modality for patients with superficial esophageal carcinoma.

Aged↗

Stimulation of steroidogenic acute regulatory protein (StAR) gene expression by D-aspartate in rat Leydig cells.

D-aspartate and human chorionic gonadotropin act synergistically to increase testosterone production in purified rat Leydig cells, and D-aspartate stimulates testosterone synthesis even in the absence of human chorionic gonadotropin stimulation. In addition, D-aspartate enhances steady-state cellular mRNA and protein levels of steroidogenic acute regulatory protein, which is a key regulatory factor in gonadal and adrenal steroidogenesis. D-aspartate therefore appears to increase testosterone production in rat Leydig cells by stimulating steroidogenic acute regulatory protein gene expression. To our knowledge, this is the first report demonstrating a direct effect of D-aspartate on gene expression in mammalian cells.

Animals↗

Activation of hematopoietic progenitor kinase-1 by erythropoietin.

Hematopoietic progenitor kinase-1 (HPK1), which is expressed predominantly in hematopoietic cells, was identified as a mammalian Ste20 homologue that, upon transfection, leads to activation of JNK/SAPK in nonhematopoietic cells. The JNK/SAPK pathway is activated by various environmental stresses and proinflammatory and hematopoietic cytokines. Upstream activators of HPK1 currently remain elusive, and its precise role in hematopoiesis has yet to be defined. We therefore examined the possible involvement of HPK1 in erythropoietin (Epo) and environmental stress-induced JNK/SAPK activation in the Epo-dependent FD-EPO cells and Epo-responsive SKT6 cells. We found that Epo, but not environmental stresses, induced rapid and transient activation of HPK1, whereas both induced activation of JNK/SAPK. A screen for HPK1 binding proteins identified the hematopoietic cell-specific protein 1 (HS1) as a potential HPK1 interaction partner. We found HPK1 constitutively associated with HS1 and that HS1 was tyrosine-phosphorylated in response to cellular stresses as well as Epo stimulation. Furthermore, antisense oligonucleotides to HPK1 suppressed Epo-dependent cell growth and Epo-induced erythroid differentiation. We therefore conclude that Epo induces activation of both HPK1 and HS1, whereas cellular stresses activate only HS1, and that the HPK1-JNK/SAPK pathway is involved in Epo-induced growth and differentiation signals.

Amino Acid Sequence↗