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Biomedical subjects

T Kanda

Publications and source records attributed to T Kanda.

At least 37 records · Page 2Linked to original sources

Effects of hormone replacement therapy on weight, abdominal fat distribution, and lipid levels in Japanese postmenopausal women.

OBJECTIVE: To investigate the effects of hormone replacement therapy (HRT) on weight, abdominal fat distribution, and fasting lipid levels in Japanese postmenopausal women (PMW). DESIGN: Prospective, 12-month-controlled clinical comparison of women with and without HRT. SUBJECTS: In all, 35 PMW with HRT (conjugated estrogens, 0.625 mg daily; medroxyprogesterone acetate, 2.5 mg daily; HRT group) and 26 PMW without HRT (control group). MEASUREMENTS: Weight, abdominal fat distribution by computed tomographic measurements, lipid profiles, and sex hormones were determined at baseline and after 12 months of treatment or observation. RESULTS: Weight did not change in any group. Visceral abdominal fat increased in controls, but not in the HRT group. Total and low-density lipoprotein cholesterol decreased, and triglyceride (TG) and high-density lipoprotein cholesterol increased in the HRT group; these did not change in the control group. When we divided women into those with android and gynoid types of abdominal fat distribution. Subjects with an android distribution showed reduced visceral fat with HRT, which also decreased the proportion of patients maintaining an android distribution. HRT did not alter abdominal fat distribution in subjects with a gynoid distribution. HRT increased serum TG in the android and the gynoid subgroups. CONCLUSION: Improved distribution of abdominal fat and fasting lipid levels except for TG may represent beneficial effects of HRT with respect to cardiovascular disease, but caution is warranted concerning TG elevation from HRT performed in PMW.

Abdomen↗

Cervical lymphadenectomy is beneficial for patients with carcinoma of the upper and mid-thoracic esophagus.

The role of cervical lymphadenectomy for thoracic esophageal cancer is controversial. This study evaluated the impact of cervical lymphadenectomy on the cervical lymph node metastasis (LNM) and survival rates of patients with esophageal cancer. We analyzed 199 patients who received radical esophagectomy with three-field lymphadenectomy. The overall 5-year survival rate was 49.4%. Cervical LNM was found in 36 (18.1%) out of the 199 patients. The 5-year survival rates of the patients with cervical LNM from upper and mid-esophageal cancers were 71.4% and 35.9%, respectively. However, none of the patients with cervical LNM from lower esophageal cancer survived more than 4 years after esophagectomy. The overall survival of patients with five or more metastatic nodes (5.9%) was significantly worse than that of patients with less than five positive nodes (45.5%). Cervical lymphadenectomy is beneficial for patients with carcinoma of the upper and mid-thoracic esophagus, and with less than five positive nodes.

Adult↗

Plasma interleukin-6 is associated with coagulation in poorly controlled patients with Type 2 diabetes.

AIMS: We investigated the relationship between interleukin (IL)-6 and coagulation, i.e. whether changes in the plasma IL-6 are associated with those in coagulation markers (D dimer and fibrinogen) after glycaemic control with sulphonylurea or insulin in poorly controlled patients with Type 2 diabetes. METHODS: We studied 42 patients with Type 2 diabetes, including 19 subsequently treated with sulphonylurea, 23 treated with insulin and 48 control subjects. All patients were in poor glycaemic control and were hospitalized for 3 weeks. At the beginning and end of treatment, we measured plasma concentrations of IL-6, fibrinogen, and D dimer. RESULTS: Plasma concentrations of IL-6 and D dimer were significantly higher in diabetic patients than in controls (P<0.0001 for both). In all patients with diabetes, the plasma concentration of IL-6 decreased significantly (P<0.001) after treatment. Changes in the plasma IL-6 during hospitalization were positively correlated with those in plasma D dimer and fibrinogen (r=0.664, P<0.0001; r=0.472, P=0.0042, respectively). Treatment with sulphonylurea or insulin caused a similar fall in the plasma IL-6 concentration with a concomitant decrease in the BMI and an equal improvement in glycaemia. CONCLUSIONS: In poorly controlled patients with Type 2 diabetes, plasma IL-6 concentrations were reduced significantly even by short-term metabolic control. As changes in the plasma concentrations of D dimer are related to plasma IL-6, plasma IL-6 may reflect a pro-coagulant as well as an inflammatory state in patients with Type 2 diabetes.

Blood Coagulation↗

Predictive value of immunohistochemical thymidylate synthase expression for histological response to Tegafur/Uracil (UFT) in oral squamous cell carcinoma.

Thymidylate synthase (TS), an enzyme involved in the DNA synthesis, is a critical target for fluoropyrimidines. We investigated the relationship between the level of tumoural TS expression and response to tegafur/uracil (UFT) in 26 patients with oral squamous cell carcinoma. The patients received peroral administration of UFT alone preoperatively. In biopsy specimens, TS expression level was assessed by the immunohistochemical staining and graded as 1+, 2+ or 3+ according to the frequency of strongly-stained tumour cells. Out of 26 tumours, 10 (38.5%), 10 (38.5%) and 6 (23.1%) cases were categorized as 1+, 2+ and 3+, respectively. The response to UFT was histologically evaluated by a grading system according to the extent of degenerative or necrotic cancer cells in surgical specimens. Results showed patients with the lower TS expression had the higher response and there was a statistically significant association between TS expression and response to UFT (P=0.031). This finding suggests that TS expression is a predictor of chemosensitivity to UFT in oral squamous cell carcinomas.

Aged↗

Hepatitis A virus VP3 may activate serum response element associated transcription.

BACKGROUND: Hepatitis A virus (HAV) infection is a major public health problem worldwide. The infection does not induce any visible cytopathic effects or interfere with macromolecular synthesis in host cells. However, the hepatitis B and C viruses have recently been reported to activate intracellular signals. To clarify the effects of HAV infection on intracellular signalling, we examined the influence of 9 FLAG-tagged HAV proteins (VP2, VP3, VP1-2A, 2B, 2C, 3A, 3BC, 3C and 3D) on signal transduction pathways. METHODS: Viral protein expression vectors were co-transfected into HeLa cells with reporter plasmids controlled by a synthetic promoter containing direct repeats of the cyclic AMP response element (CRE), serum response factor (SRF), activator protein 1 (AP-1), nuclear factor kappaB (NF-kappaB) or serum response element (SRE). Cells were harvested 42 h after transfection and luciferase assays were performed. Viral protein activation twice that of the control was defined as significant. RESULTS: VP3 induced an SRE-associated signal 2.2 +/- 0.3 times higher than that of control. VP3 did not activate CRE-, SRF-, AP-1- or NF-kappaB- associated signalling. The other HAV proteins tested also failed to induce these pathways. CONCLUSIONS: HAV interacts with the host signalling mechanism, and HAV VP3, different from HBX and hepatitis C core protein, may activate only SRE-associated intracellular signalling, a pathway associated with cell proliferation and differentiation.

Blotting, Western↗

Distribution of hepatitis B viral genotypes and mutations in the core promoter and precore regions in acute forms of liver disease in patients from Chiba, Japan.

BACKGROUND: Although it has been reported that different hepatitis B virus (HBV) genotypes induce different clinical characteristics in patients with chronic liver diseases (CLD), there have been few reports that have detailed the distribution of HBV genotypes in acute forms of liver disease. METHODS: HBV genotypes were determined in 61 patients who had acute forms of liver disease (45 had acute self limited hepatitis (AH) and 16 had fulminant hepatitis (FH)) and in 531 patients with CLD, including 19 patients with severe acute exacerbation of CLD. We also analysed the enhancer II, core promoter, and precore region sequences for the presence of mutations. RESULTS: Expression of genotype B in patients with acute forms of liver disease was significantly greater than in those with CLD (39.3% v 11.7%, respectively; p<0.001). Furthermore, expression of genotype B was significantly greater in patients with FH than in those with AH (62.5% v 31.1%, respectively; p=0.027). The precore mutation A1896 and the core promoter mutation at nt 1753 and 1754 were found more frequently in FH than in AH, and genotype B was predominant in FH regardless of the presence of these mutations. CONCLUSIONS: HBV genotype B was found more frequently in patients with acute forms of liver disease than in patients with CLD, and more frequently in patients with FH than in those with AH. These results suggest that this HBV genotype may induce more severe liver damage than other viral genotypes, at least in patients from Chiba, Japan.

Acute Disease↗

Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency?

Acute axonal polyneuropathy and Wernicke-Korsakoff encephalopathy developed simultaneously in three patients. Nerve conduction studies (NCS) detected markedly decreased compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) with minimal conduction slowing; sympathetic skin responses (SSRs) were also notably decreased. Sural nerve biopsies showed only mild axonal degeneration with scattered myelin ovoid formation. The symptoms of neuropathy lessened within two weeks after an intravenous thiamine infusion. CMAPs, SNAPs, and SSRs also increased considerably. We suggest that this is a new type of peripheral nerve impairment: physiological conduction failure with minimal conduction delay due to thiamine deficiency.

Acute Disease↗

Characterization of the kynurenine 3-monooxygenase gene corresponding to the white egg 1 mutant in the silkworm Bombyx mori.

Kynurenine 3-monooxygenase (KMO, EC 1.14.13.9), which catalyzes the oxidation of kynurenine to 3-hydroxykynurenine, is involved in the synthesis of ommochrome pigments in insects. A silkworm mutant, white egg 1 ( w-1), has been shown to be deficient in this enzyme activity. The mutant is characterized morphologically by its white eyes and the fact that the females lay white eggs. To analyze the relationship between the KMO gene and the mutation, we first determined the entire sequence of a full-length 2.0-kb cDNA and examined its expression pattern in the wild type. The cDNA sequence contains one ORF encoding a polypeptide of 456 amino acids, and transcripts were detected in the larval Malpighian tubules and the pupal ovaries, but not in other tissues. Southern analysis and nucleotide sequencing showed that the KMO gene is present in a single copy and consists of ten exons distributed over a 16-kb region. Comparison of the transcripts between the wild type and mutant silkworms showed that the wild type expressed a single transcript, whereas the mutant exhibited markedly reduced amounts of two transcripts with sizes of 2.0 kb and 1.8 kb. Nucleotide sequence analysis of these mutant transcripts indicated that sequences corresponding to the ninth and tenth exons were missing. Inverse PCR and Southern analysis of the mutant gene demonstrated that the corresponding genomic region was deleted in the w-1 mutant.

Amino Acid Sequence↗

Impact of calcium antagonists on bleeding time in patients with chronic renal failure.

Haemorrhagic diathesis develops in chronic renal failure, in which calcium antagonists are used widely as antihypertensive agents. Although calcium antagonists are reported to impair platelet function, it has not been examined whether calcium antagonists alter bleeding time. The present study was conducted to clarify whether calcium antagonists affect bleeding time in chronic renal failure. Patients with chronic renal failure without and with calcium antagonists were enrolled (n = 156), and bleeding time (Ivy's method) as well as blood parameters (BUN, creatinine, platelet counts, and haemoglobin) were compared in patients with normal and prolonged bleeding time. Among patients not taking calcium antagonists (n = 34), three cases manifested prolonged bleeding time, whereas abnormal bleeding time was observed in 31 patients out of 122. Positive correlations were observed between bleeding time and BUN in both calcium antagonist-untreated (r = 0.46) and -treated groups (r = 0.25). The odds ratio for prolongation of bleeding time in patients taking calcium antagonists was 3.52 (95% CI, 1.01-12.33). In 12 calcium antagonist-treated patients with prolonged bleeding time, the withdrawal of calcium antagonists markedly shortened bleeding time (from 11.3 +/- 0.8 to 5.4 +/- 0.8 min, P < 0.05, n = 12). In contrast, in the additional group (n = 9), the continued treatment with calcium antagonists had no effect on bleeding time (from 11.7 +/- 0.9 to 10.0 +/- 1.0 min). Despite the inhibitory effect of calcium antagonists on bleeding time, no clinically serious events associated with haemorrhagic diathesis developed. In conclusion, calcium antagonists prolong bleeding time in patients with chronic renal failure. The subclinical (laboratory) effect of calcium antagonists however is not necessarily associated with haemorrhagic events of clinical significance.

Aged↗

Significance of immunohistochemical nodal micrometastasis as a prognostic indicator in potentially curable oesophageal carcinoma.

BACKGROUND: The number of positive lymph nodes is an important prognostic predictor in patients with oesophageal cancer. However, the significance of nodal micrometastasis in patients with overt nodal metastasis is unknown. The aim of this study was to clarify the clinical implications of nodal micrometastasis in patients undergoing curative oesophagectomy for oesophageal cancer. METHODS: Cervical, mediastinal and abdominal lymph nodes systematically removed from 104 patients with oesophageal cancer were examined immunohistochemically to detect cells that stained positively for cytokeratins with the monoclonal antibody cocktail AE1/AE3. The postoperative course and survival rates were compared among patients with and without micrometastases, after numerical classification of overt metastatic nodes (none, between one and four, five or more). RESULTS: Univariate analysis showed T stage, nodal micrometastasis and number of overt nodal metastases to be significant prognostic factors after oesophagectomy. Multivariate analysis revealed nodal micrometastasis and number of overt nodal metastases to be independent prognostic factors. The presence of micrometastases had a significant adverse effect on postoperative survival in patients with no overt metastasis and in patients with one to four overt metastatic nodes, but no such impact in patients with five or more overt metastatic nodes. CONCLUSION: Assessment of nodal status by both histological examination for overt metastases and immunohistochemical examination for micrometastases is useful in stratifying patients undergoing curative oesophagectomy.

Adult↗

Induction of the white egg 3 mutant phenotype by injection of the double-stranded RNA of the silkworm white gene.

Injection of double-stranded RNA (dsRNA) corresponding to the silkworm white gene (Bmwh3) into preblastoderm eggs of the wild-type silkworm induced phenotypes similar to those observed with mutants of the white egg 3 locus (10-19.6). The induced phenotypes were characterized by the presence of white eggs and translucent larval skin. Northern analysis showed that the expression of the endogenous Bmwh3 gene in the injected embryos was distinctly depressed. Furthermore, the injection of the GFP dsRNA inhibited the expression of the GFP gene from a plasmid co-injected with the dsRNA but did not depress the expression of the Bmwh3 gene. These findings demonstrate that sequence-specific RNA interference occurred in the silkworm. We conclude from the results that the RNA interference can be applied as a tool for the analysis of the gene function in the lepidopteran insects.

Animals↗

Obesity and lipid profiles in middle aged men and women in Tanzania.

OBJECTIVE: To examine the relationship between obesity and lipid profiles and to compare the effects of total obesity and central adiposity on lipids in three locations in Tanzania. DESIGN: Cross-sectional epidemiological study. SETTING: Three areas in Tanzania: Dar es Salaam (urban), Handeni (rural) and Monduli (pastoralists), in August 1998. SUBJECTS: Five hundred and forty five men and women from a random sample of 600 people aged 46-58 years. MAIN OUTCOME MEASURES: Mean BMI, waist circumference, WHR, TC, HDL-C, LDL-C, TG and LDL/HDL ratio. Prevalence rates of overweight,obesity, central obesity and dyslipidaemia. RESULTS: As compared to men, women had higher BMI (24.7 versus 22.5 kg/m2, p<0.0001), waist circumference (92.4 versus 89.1 cm, p<0.05), TC (4.9 versus 4.2 mmol/L, p<0.0001) and LDL-C (3.3 versus 2.6 mmol/L, p<0.0001). The urban population demonstrated higher levels of lipid factors than the rural population (TC, men 4.8 mmol/L; women 5.3 mmol/L, p<0.0001; TG, men 3.6 mmol/L; women 3.7 mmol/L, p<0.0001, LDL-C, men 2.8 mmol/L, p<0.0001). BMI and waist circumference correlated positively with serum TC, TG, and LDL-C in both genders. Stepwise regression analysis showed that BMI predicted triglyceride concentration in men (p<0.05) and women (p<0.0001). Waist circumference predicted levels of TC in women only (p<0.0001) and of LDL-C in both genders (men p<0.05, women p<0.0001). The prevalence of overweight, obesity and central obesity were significantly higher in urban than in rural areas in both men and women. Compared to lean subjects, obese men and women had significantly higher mean serum TC, TG, LDL-C and a higher prevalence of dyslipidaemia. The mean levels of TC, TG and LDL cholesterol increased across successive increases in BMI and waist circumference quintiles in both genders. CONCLUSION: Subjects from the urban area had greater lipid abnormalities related to obesity than those from the rural area and that, central adiposity had a greater effect on total cholesterol and LDL cholesterol among women than was BMI.

Body Mass Index↗

Preparation strategy for uniformly sized, polymer-based HPLC packing materials having practically acceptable column efficiency. 1. Copolymerization technique.

Uniformly sized, polymer-based packing materials affording excellent chromatographic performance in semimicro HPLC were prepared from mixtures of alkyl methacrylate and glycerol dimethacrylate by a copolymerization technique using a multistep swelling and polymerization method. A column efficiency of up to 13000 plates was obtained for a 2-mm-i.d. x 150-mm column with beads prepared from a 1:1 (v:v) mixture of an alkyl methacrylate and glycerol dimethacrylate. The packing materials exhibit a considerable improvement in column efficiency, as demonstrated on the separation of polyaromatic hydrocarbons (PAHs) having a relatively long retention time, which thus far has been a serious problem of polymer-based packing materials. Detailed studies suggested a rather limited optimum pore size, and its distribution was depicted to get the excellent column efficiency on polymer-based packing materials.

Journal Article↗

Cardiovascular risk factors in Tanzania: a revisit.

In this assessment of cardiovascular risk factors, we examined the prevalence of selected risk factors according to the World Health Organisation (WHO) CARDIAC Study protocol and compared them with a similar study conducted more than a decade ago. The survey was carried out in Dar es Salaam (D, urban), Handeni (H, rural) and Monduli (Mo, semi-nomadic area). Subjects aged 47-57 were recruited randomly for blood pressure and anthropometrical measurements, 24 h urine collection and blood sampling. A structured questionnaire was used to obtain dietary information. The 1998 survey studied 446 subjects, while the 1987 survey included 496 men and women. The measured weight, body mass index (BMI) and prevalence of obesity (BMI > or = 30 kg/m(2)) increased significantly among women in the 1998 survey in rural Handeni and urban Dar. The overall prevalence of obesity was higher for women in the most recent survey (22.8%, P < 0.0001). Diastolic blood pressure (DBP) was higher in the most recent survey for women in Handeni. The overall prevalence of hypertension (blood pressure > 160/95 mmHg, or antihypertensive drug use), rose to 41.1% in 1998, (P < 0.001) for men and to 38.7% (P < 0.05) for women. The mean total serum cholesterol and prevalence of hypercholesterolaemia increased significantly in the most recent survey in the three studied areas. The overall prevalence of hypercholestrolaemia (serum cholesterol > 5.2 mmol/l) was higher in the 1998 survey for both men (21.8%, P < 0.0001) and women (54.0%, P < 0.0001). The mean HDL cholesterol increased significantly in the most recent survey, with a significant reduction in the mean atherogenic index, though these were still at higher levels (men 5.8, P < 0.0001; women 5.1, P < 0.0001 vs. 1987). A strong positive correlation was observed between blood pressure (SBP and DBP) and body mass index, total serum cholesterol and sodium to potassium ratio. These data suggest that for the past decade there has been an increase in the mean levels and prevalence of selected cardiovascular risk factors in Tanzania.

Blood Pressure↗

Characterization of the bi-directional transcriptional control region between the human UFD1L and CDC45L genes.

The human UFD1L and CDC45L genes, adjacently located in the head-to-head direction on chromosome 22q11, are separated by a 884 base-pair (bp) segment constituting the putative transcriptional control region. In this region we mapped one transcription start site at 69 bp upstream of UFD1L gene, and one major and one minor start sites at 76 bp and 503 bp upstream of CDC45L gene, which are to center in the putative core promoters designated as P(UFD1L), P(CDC45L/major), and P(CDC45L/minor), respectively. The three core promoters lacked a TATA-motif and had a high GC-content. To determine the approximate ranges for the regulatory promoters, the 884-bp fragment or those with a series of deletions were placed between firefly and renilla luciferase genes present in the head-to-head direction in a single plasmid, and the resulting plasmids were assayed for the two transiently induced enzyme activities. The P(UFD1L) and P(CDC45L/major) regulatory promoters were within 418 and 454 bp upstream of the respective start sites and their greater parts were not overlapping. The activity of P(CDC45L/minor) regulatory promoter was markedly enhanced when P(CDC45L/major) and its regulatory promoter were deleted. The deletion analyses revealed the basal activities of the three core promoters, which were enhanced by approximately twofold by the respective regulatory promoters, on the transfected DNA templates.

Adaptor Proteins, Vesicular Transport↗

Unusually short distances between the carbonyl oxygen and the tin atom in RCOSMR'3 (M = Ge, Sn, Pb): the importance of intramolecular n(O) --> sigma*(MS) orbital interactions.

[structure: see text]. We found that the C=O.Sn distance in RCOSSnR'3 was shorter than the C=O.Ge distance in RCOSGeR'3 and theoretically confirmed that the orbital interactions between the nonbonding orbitals on the carbonyl oxygen (n(O)) and the sigma*(SnS) orbitals were important in regard to the shortness.

Journal Article↗

4,5,9,10-Tetrahydro-1,4-ethanobenz[b]quinolizine as a prodrug for its quinolizinium cation as a ligand to the open state of the TCP-binding site of NMDA receptors.

A new derivative of 4,5,9,10-tetrahydro-1,4-ethanobenz[b]quinolizine (2) has been designed as a prodrug for its quinolizinium cation (1) that is a potent antagonist of the TCP-binding site of NMDA receptors at the open state. The 11C-labeled 2 showed high accumulation of radioactivity in the brain in an in vivo biodistribution study. The speculation of 2 as a prodrug of 1 has been proven by the fact that 1 was observed in a high ratio to 2 in an analysis by RP-HPLC of the brain homogenates.

Animals↗