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Biomedical subjects

N Tanaka

Publications and source records attributed to N Tanaka.

At least 361 records · Page 20Linked to original sources
PubMed2000

The initial step of the thermal unfolding of 3-isopropylmalate dehydrogenase detected by the temperature-jump Laue method.

A temperature-jump (T-jump) time-resolved X-ray crystallographic technique using the Laue method was developed to detect small, localized structural changes of proteins in crystals exposed to a temperature increase induced by laser irradiation. In a chimeric protein between thermophilic and mesophilic 3-isopropylmalate dehydrogenases (2T2M6T), the initial structural change upon T-jump to a denaturing temperature (approximately 90 degrees C) was found to be localized at a region which includes a beta-turn and a loop located between the two domains of the enzyme. A mutant, 2T2M6T-E110P/S111G/S113E, having amino acid replacements in this beta-turn region with the corresponding residues of the thermophilic enzyme, showed greater stability than the original chimera (increase of T:(m) by approximately 10 degrees C) and no T-jump-induced structural change in this region was detected by our method. These results indicate that thermal unfolding of the original chimeric enzyme, 2T2M6T, is triggered in this beta-turn region.

3-Isopropylmalate Dehydrogenase↗
PubMed2000

Brain acetylcholinesterase activity in Alzheimer disease measured by positron emission tomography.

Brain acetylcholinesterase activity was measured in 14 patients with Alzheimer disease and 14 age-matched control subjects by positron emission tomography with a radioactive acetylcholine analogue. Kinetic analysis was performed to calculate k3, an index of acetylcholinesterase activity. The k3 values were significantly reduced in the neocortex, hippocampus, and amygdala of all patients with Alzheimer disease, suggesting a loss of cholinergic innervation from the basal forebrain. Most profound reductions of k3 values were observed in the temporal (-30%) and parietal cortices (-31%), although reductions of k3 values were relatively uniform in the cerebral neocortex. This technique may be a powerful tool for early diagnosis of Alzheimer disease and also for therapeutic monitoring of acetylcholinesterase inhibitors in Alzheimer disease.

Acetylcholinesterase↗
PubMed2000

The usefulness of serial changes in serum CA19-9 levels in the diagnosis of pancreatic cancer.

We examined serial changes in serum CA19-9 levels in patients with pancreatic cancer (PC) or chronic pancreatitis (CP) to clarify whether these changes are useful in the diagnosis of PC. We chose II PC patients in whom serum CA19-9 levels had been measured serially before a definitive diagnosis of PC had been established. We also examined serial changes in serum CA19-9 levels during the recent 1-year follow-up period in 21 CP patients. Serial changes in these levels were classified into the following five types; normal, elevated, increased, decreased, and other. Of the 11 PC patients, seven patients (64%) showed the increased type, whereas none showed the normal type. However, among the CP patients, 10 patients (48%) showed the normal type and only one (5%) showed the increased type. The proportion of the increased type among PC patients was significantly higher than that among CP patients. In conclusion, serial changes in serum CA19-9 levels may be useful to differentiate between PC and CP. Close follow-up with various diagnostic modalities may be required for patients whose serum CA19-9 levels increase to more than twofold the initial level, because such findings are highly suggestive of PC.

Adult↗
PubMed2000

Crystallization and initial X-ray analysis of alkaline xylanase.

Crystals of alkaline xylanase (xylanase J) from alkaliphilic Bacillus sp. 41M-1 were grown by decreasing the temperature of the protein solution. Initial X-ray analysis of the crystal showed a tetragonal system with space group P4(1) or P4(3) and unit-cell parameters a = b = 115.7, c = 46.0 A. Assuming two molecules per asymmetric unit, V(m) = 2.31 A(3) Da(-1). The crystals diffract X-rays to 2.6 A resolution at 100 K.

Bacillus↗
PubMed2000

Enhancement in the perfection of orthorhombic lysozyme crystals grown in a high magnetic field (10 T).

Orthorhombic crystals of hen egg-white (HEW) lysozyme were grown in a homogeneous and static magnetic field of 10 T. All crystals grown at 10 T were oriented such that their crystallographic c axes were parallel to the magnetic field direction and showed a narrower average full-width at half-maximum (FWHM) of the rocking curve than those grown at 0 T. Rocking-width measurements were made at the BL-10A station at the Photon Factory, Tsukuba, Japan, using a high-resolution vertical-type four-circle diffractometer. Crystal perfection was evaluated using the FWHM of the rocking curve; the effects of the magnetic field on the quality of the crystals were examined by comparison of the FWHM of seven crystals grown at 10 and 0 T. The FWHMs of the reflections along the a, b and c axes decreased by 23.5, 35.3 and 27.8%, respectively, and those of other general reflections decreased by 17.4-42.2% in the crystals grown at high magnetic field. These results clearly showed that a magnetic field of 10 T improved the crystal perfection of the orthorhombic lysozyme crystals. As a result, the maximum resolution of X-ray diffraction increased from 1.3 A at 0 T to 1.13 A at 10 T. The magnetic field also affected the dimensions of the unit cell, increments being 0.2% for the a and c axes and 0.1% for the b axis, respectively. These facts suggest that the application of a high magnetic field during crystallization might result in remarkable enhancements in the diffraction power of protein crystals having magnetic anisotropy.

Animals↗
PubMed2000

Suppression of tumor growth and downregulation of platelet-derived endothelial cell growth factor / thymidine phosphorylase in tumor cells by angiogenesis inhibitor TNP-470.

We investigated the effects of the angiogenesis inhibitor TNP-470 on human lung squamous cell carcinoma cell lines H226B and H226Br both in vivo and in vitro. H226B was established from human lung squamous cell carcinoma and H226Br was established from a brain metastatic lesion of H226B in nude mice. Nude mice inoculated with these cells were treated with 30 mg / kg of TNP-470 subcutaneously every other day. At this dose, TNP-470 only significantly suppressed the growth of H226Br tumor, but not H226B tumor. Attempts to use a high dose of TNP-470 (100 mg / kg) resulted in a severe loss of body weight. Immunohistochemical studies showed marked tumor vascularization in H226Br tumor, but the formation of new blood vessels was suppressed by 30 mg / kg of TNP-470. Investigation of the mechanism of anti-angiogenic effects of TNP-470 in vivo showed that the expression and the activity of platelet-derived endothelial cell growth factor / thymidine phosphorylase (PD-ECGF / dThdPase) in H226Br tumor was significantly suppressed by 30 mg / kg of TNP-470. Furthermore, TNP-470 inhibited cell growth of cultured H226Br dose-dependently at concentrations of 1 microg / ml. Immunoblot analysis revealed H226Br cells gave a stronger PD-ECGF signal than H226B cells, and the expression of PD-ECGF / dThdPase in H226Br was also suppressed by treatment with TNP-470 at 0.1 microg / ml. No change in basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) was noted in these cell lines. Our results suggested that TNP-470 acts, at least in part, by downregulation of PD-ECGF / dThdPase in this cell line.

Angiogenesis Inhibitors↗
PubMed2000

Mean corpuscular volume may be a useful index of risk for colorectal adenoma in middle-aged Japanese men.

OBJECTIVE: It has been reported that alcohol intake and folate deficiency are associated with an increased risk of colorectal adenomas and carcinomas. Mean corpuscular volume (MCV) of red blood cells has been reported to be increased in these conditions. The purpose of this study was to assess the association between MCV and risk of colorectal adenoma. METHODS: The subjects were 497 middle-aged (45-65 yr old) men who underwent both barium enema examination and total colonoscopy. The subjects answered a questionnaire regarding their alcohol consumption history, and their blood samples were analyzed. The subjects were divided into four groups three times: with or without alcoholism, and with or without adenoma according to alcohol intake, and according to the MCV value. Various variables were compared among the groups, and the odds ratios of adenoma were calculated. RESULTS: The MCV was higher in the alcoholic group than in the nonalcoholic group (p < 0.01) and in patients with adenoma than in those without adenoma (p < 0.0001). When the subjects were stratified by alcohol intake, the MCV value had a higher significant difference than alcohol intake, between patients with adenoma and those without adenoma. As for the MCV value, the odds ratio (95% confidence interval) of adenoma was 1.00 (referent); (<92), 1.20 (0.71-1.69); (> or =92 but <95), 2.61 (2.07-3.15); (> or =95 but <98); and 3.62 (2.99-4.25); (> or =98). CONCLUSION: A high MCV value may be used as a simple index of the risk of colorectal adenomas, regardless of alcohol consumption.

Adenoma↗
PubMed2000

Cytogenetic analysis shows that the unusually large chromosome in the sex-limited pB silkworm (Bombyx mori) strain consists of three chromosomes.

We have discovered an inordinately large chromosome pair at the pachytene stage in the oocyte of the sex-limited pB (black larval marking) silkworm (Bombyx mori) strain (TWPB). We have analyzed the composition and arrangement of this large chromosome. A genetic linkage analysis shows that the large chromosome is made up of the W chromosome, the second chromosome fragment (pB fragment), and the fifth chromosome (linkage group) containing at least the region from map position 0.0 to 40.8. We also observed a sex heterochromatin body (SB) that we deduced to be made up of condensed W chromosomes. The number of SBs in each female nucleus among the sucking stomach cells of the TWPB strain was variable. Evidently, the W chromosome of the TWPB strain is attached to another chromosome. The composition of the W chromosome, the second chromosome fragment, and the fifth chromosome was studied through linkage analysis for these three chromosomes. We used two strains derived from the TWPB strain, the sex-limited pM (moricaud larval marking)-like (TWPML) and the autosomal pM-like (T5PML). The results show that the TWPML strain originates through a detachment of the fifth chromosome from the large chromosome of the TWPB strain, and the T5PML strain originates through a detachment of the W chromosome from that. Accordingly, the large chromosome of the TWPB strain is arranged in the order W chromosome--second chromosome fragment--fifth chromosome.

Animals↗
PubMed2000

Roles of the AGE-RAGE system in vascular injury in diabetes.

This study concerns whether advanced glycation endproducts (AGE) are related to microvascular derangement in diabetes, exemplified by pericyte loss and angiogenesis in retinopathy and by mesangial expansion in nephropathy. AGE caused a decrease in viable pericytes cultivated from bovine retina. On the other hand, AGE stimulated the growth and tube formation of human microvascular endothelial cells (EC), this being mediated by autocrine vascular endothelial growth factor. In AGE-exposed rat mesangial cells, type IV collagen synthesis was induced. Those AGE actions were dependent on a cell surface receptor for AGE (RAGE), because they were abolished by RAGE antisense or ribozyme. The AGE-RAGE system may thus participate in the development of diabetic microangiopathy. This proposition was supported by experiments with animal models; several indices characteristic of retinopathy were correlated with circulating AGE levels in OLETF rats. The predisposition to nephropathy was augmented in RAGE transgenic mice when they became diabetic.

Animals↗
PubMed2000

Comparison of quantitations of viral load in varicella and zoster.

The pathogenesis of varicella and zoster and the effects of antiviral treatment were investigated using real-time PCR for varicella-zoster virus (VZV) DNA in skin lesions and peripheral blood. A higher occurrence of viremic VZV DNA was observed in varicella than in zoster. Acyclovir treatment resulted in marked suppression of viremia in varicella.

Acyclovir↗
PubMed2000

Continuous monitoring of nitric oxide release induced by cholecystokinin from the choledochal sphincter in guinea pigs.

BACKGROUND/AIMS: Many in vitro studies in the choledochoduodenal junction of the guinea pig have shown that cholecystokinin (CCK) contracts the sphincter of Oddi (SO). This study, using the choledochal sphincter of the guinea pig as the SO, evaluates the hypothesis that effects of CCK on the SO were mediated by nitric oxide (NO). METHODS: Spontaneous motility and effects of CCK on the choledochal sphincter were recorded using a constant-perfusion technique, and direct measurement of NO release using a specific NO sensor was performed at the same time. RESULTS: CCK-8 decreased the phasic wave amplitude of the choledochal sphincter, and increased NO release. N(G)-L-arginine-methyl-ester (L-NAME), an inhibitor of NO synthase, increased the spontaneous motility and converted the CCK-induced inhibitory response into an excitatory response. L-NAME also reduced NO release and abolished the increase of NO that had been caused by CCK-8. These effects were reduced by treatment with L-arginine (L-Arg). L-Arg application enhanced NO release, and recovered the increase of NO by CCK-8. CONCLUSION: These studies demonstrate that CCK relaxes the choledochal sphincter and this relaxant response is mediated by NO.

Animals↗
PubMed2000

Multiple tumors and a novel E2F-4 mutation. A case report.

Defects in the DNA mismatch-repair are known to cause microsatellite instability (MSI) in hereditary nonpolyposis colorectal cancer (HNPCC) as well as sporadic colorectal cancer (CRC). We previously reported that the E2F-4 gene, which encodes an important transcription factor in cell cycle control, had frequent tumor-specific mutations at the trinucleotide coding region microsatellite (CAG)n in a subset of human sporadic CRC with MSI. We report a 65-year-old man with triple tumors in the abdomen, including colon cancer, stomach cancer, and lipoma of the retroperitoneum, with the analysis of E2F-4 mutation. We report the first case of colon cancer with a homozygous E2F-4 mutation along with a detailed analysis of other cancer related genes as well as a prognosis.

Adult↗
PubMed2000

Establishment and characterization of two new rectal neuroendocrine cell carcinoma cell lines.

BACKGROUND: Human colorectal neuroendocrine cell carcinoma (NEC) is a rare disease with a poor prognosis. The biological behavior of NEC remains poorly understood. MATERIALS AND METHODS: We established two new NEC cell lines from a patient with rectal neuroendocrine carcinoma, NECS-P and NECS-L from the primary tumor and a liver metastasis, respectively. We investigated the biological differences between the two cell lines to study the mechanisms involved in liver metastasis. RESULTS: There was no difference between NECS-P and NECS-L in the morphological, ultrastructural and immunohistochemical studies. After addition of TGF-beta(1), the doubling times of NECS-P were increased in a dose-dependent manner relative to untreated cells, whereas TGF-beta(1) had no effect on NECS-L. The attachment and chemotactic response of the two cell lines were not enhanced by TGF-beta(1). The invasive capacity and the production of matrix metalloproteinase-2 (MMP-2) were significantly increased only in NECS-L following the addition of TGF-beta(1). When anti-MMP-2 antibody was added to the medium with TGF-beta(1), NECS-L invasion was inhibited. CONCLUSION: It is considered that these differences are important to understand the mechanisms of liver metastasis of NEC.

Carcinoma, Neuroendocrine↗
PubMed2000

Genetic aberrations detected by comparative genomic hybridization in ovarian clear cell adenocarcinomas.

Genetic abnormalities were detected by comparative genomic hybridization (CGH) in 12 ovarian clear cell adenocarcinomas. DNA sequence copy number abnormalities (CNAs) occurring in more than 20% of the cancers included increased copy numbers of 8q11-q13, 8q21-q22, 8q23, 8q24-qter, 17q25-qter, 20q13-qter and 21q22-qter and reduced copy numbers of 19p. Increases in copy numbers of 8q11-q13, 8q21-q22, 8q23 and 8q24-qter occurred more frequently in disease-free patients than in recurrent/non-surviving patients (p < 0.05). However, increases in copy numbers of 17q25-qter and 20q13-qter occurred more frequently in recurrent/non-surviving patients than in disease-free patients (p < 0.05). Furthermore, increases in copy numbers of 17q25-qter and 20q13-qter occurred together (p < 0.05). Additionally, there were negative correlations between increases in copy numbers of 8q21-q22 and 17q25-qter, and between 8q21-q22 and 20q13-qter (p < 0.05). It appears that ovarian clear cell adenocarcinomas can be classified into two subtypes, one being cancer with an increase in copy numbers of 8q and the other being cancer with increases in copy numbers of 17q25-qter and 20q13-qter.

Adenocarcinoma, Clear Cell↗
PubMed2000

Persistent TT virus infection does not contribute to the development of non-A to -G hepatocellular carcinoma. A case-control study of 19 patients in Japan.

We tested the sera of patients with non-A, non-B, non-C, non-G (non-A to -G) hepatocellular carcinoma (HCC) for the presence of TT virus (TTV) DNA and clinicopathologically elucidated the relationship between TTV infection and hepatocarcinogenesis. The study cohort consisted of 19 patients with non-A to -G HCC. Detection of TTV DNA was performed by the nested polymerase chain reaction according to a previously published method. TTV DNA was detected in the sera of 9 (47.4%) of the 19 patients with non-A to -G HCC. The clinical background factors and blood biochemical parameters of the TTV-DNA-positive and -negative HCC patients did not significantly differ. Three TTV-DNA-positive and 2 TTV-DNA-negative patients underwent surgical resection of the HCC. The histological findings in the non-cancerous liver tissue of the TTV-DNA-positive and -negative patients did not significantly differ. In conclusion, TTV infection does not affect the features of non-A to -G HCC.

Aged↗
PubMed2000

Trisomy 14 with thrombocytosis and monocytosis.

It has been reported that trisomy 14 is associated with myeloid malignancies, but a case with increased platelet count has also been reported. However, the clinical significance of trisomy 14 is still uncertain. We report a patient with trisomy 14 with thrombocytosis and a gradual increase in monocytosis. He was treated with hydroxyurea, cytarabine and aclarubicin in low doses and his quality of life was maintained for a period of about 1 year from blastic crisis. Hydroxyurea, cytarabine or aclarubicin in low doses may be the treatment of choice for trisomy 14 patients with respect to the patients' quality of life.

Aclarubicin↗
PubMed2000

Evaluation of splenic circulation after spleen-preserving distal pancreatectomy by dividing the splenic artery and vein.

BACKGROUND/AIM: In the present study, we investigated the acute and late phases of splenic circulation after spleen-preserving distal pancreatectomy (SPDP) involving the division of splenic vessels. METHODS: An acute phase of splenic circulation was evaluated by laser flow meter and the late phase was estimated by (99m)Tc-galactosyl human serum albumin spleen scintigraphy. RESULTS: Splenic blood supply, evaluated by laser flow meter immediately after SPDP, dropped to one half of the prior blood supply. However, blood supply recovered 10 days after SPDP, as estimated by (99m)Tc-galactosyl human serum albumin spleen scintigraphy. CONCLUSION: There are two variations of SPDP: SPDP without preservation of the splenic artery and vein, and SPDP with preservation of the splenic artery and vein. The disadvantage of the former is the resulting decrease in splenic blood supply. The present findings may help to make up for this disadvantage.

Humans↗