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Biomedical subjects

T Sakata

Publications and source records attributed to T Sakata.

At least 109 records · Page 6Linked to original sources

Foods and nutrients in relation to bladder cancer risk: a case-control study in Aichi Prefecture, Central Japan.

To elucidate the role of diet in the etiology of bladder cancer, we conducted a case-control study from 1996 to 1999 in Aichi Prefecture, Central Japan. Cases were patients newly diagnosed with bladder cancer, and one hospital control was selected for each case, matching gender, age, and hospital. A well-validated food frequency questionnaire was adopted to estimate intakes of nutrients and food groups. Odds ratios (ORs) adjusted for smoking and occupational history were computed using conditional logistic models. The analyses based on 297 cases and 295 controls revealed the following. 1) The more the intake of milk and dairy products, the lower the OR; the ORs across quartiles in all subjects were 1.02, 0.73, and 0.52. Fruit intake was negatively associated with the risk, particularly in men (ORs across quartiles = 0.76, 0.77, and 0.52). Green-yellow vegetables were associated with a decreased risk in the highest quartile of consumption in men (OR = 0.57). 2) Dietary intakes of retinol and saturated fatty acids were related to a reduced risk in all subjects (ORs across quartiles = 0.75, 0.54, and 0.66 and 0.55, 0.54, and 0.60, respectively). Monounsaturated fatty acids had an inverse association with bladder cancer risk in men.

Adult↗

Atrial double potentials associated with the elimination of the electrical connection between the coronary sinus (CS) and the left atrium in two cases of Wolff-Parkinson-White syndrome with a CS-connected accessory pathway.

A curious retrograde conduction in connection with the coronary sinus (CS) musculature was observed in 2 patients. After the failed ablation procedure, the atrial electrogram during ventricular pacing presented double potentials, the first component of which was sharp and with an activation sequence that was the same before ablation (CS distal to proximal). The second component of the double potentials was dull and had a decremental property; its activation sequence was in reverse (proximal to distal). In both cases, the first component disappeared after successful ablation. These findings suggest that the first component was the CS electrogram conducted over the accessory pathway and the second component was the left atrial electrogram conducted through the inter-atrial septum. The separation of each electrogram is probably the result of a block between the accessory pathway connected to the CS musculature and the left atrium. These are unusual cases of an accessory pathway connected to the CS musculature, which separates the left atrial myocardium at the distal portion from the ostium.

Adult↗

Preceding stimulus frequency-dependent potentiation of the postrest shortening of the action potential duration in rabbits.

Action potential duration (APD) in rabbit ventricular myocardium shortens after a rest period (postrest shortening). However, the effects of preceding stimulus frequency on the postrest shortening have not been elucidated. We recorded transmembrane action potentials (TAPs) and monophasic action potentials (MAPs) from the rabbit ventricle. In in vitro experiments. repetitive regular stimuli (S1) at cycle lengths ranging between 500 to 3000 ms were followed by a single extrastimulus (S2) at a coupling interval of 5000 ms. A decrease in S1S1 interval resulted in a progressive shortening of the duration of TAP (TAPD) elicited by S2 (S2-TAPD), which was potentiated by increasing extracellular calcium concentration ([Ca2+]o) or application of ouabain and was inhibited by lowering [Ca2+]o or verapamil. Application of ryanodine was most effective in lengthening S2-TAPD following a short S1S1 interval. 4-aminopyridine and E4031 caused marked lengthening of S2-TAPD when S1S1 was long. However, the lengthening effect was attenuated and disappeared with a shorter S1S1 interval. In in vivo experiments, regular ventricular pacing (S1) at cycle lengths ranging between 250 to 1000 ms was followed by a single extrastimulus (S2) with a coupling interval (S1S2) of 1500 ms. A decrease in the S1S1 interval also resulted in progressive shortening of the duration of MAP elicited by S2. Our results indicate that the postrest shortening is potentiated by an increase in the preceding stimulus frequency in the rabbit ventricle, in which the function of sarcoplasmic reticulum may play a significant role.

Action Potentials↗

[The risk of colorectal adenomatous polyp in relation to serum total cholesterol levels in Japanese men classified by age group].

In order to investigate the relationship between the risk of colorectal cancer and serum total cholesterol (TC) levels, we studied the relationship between the risk of colorectal adenomatous polyp and high TC levels in Japanese men aged from 40 to 59 at a manufacturing company. We first diagnosed 283 subjects as having adenomatous polyp (AD) or normal (C), identified by means of an immunological fecal occult blood detection test and total colonofiberscopic examination (TCF), and then selected 94 subjects after excluding the patients with diseases possibly influencing TC. We classified the subjects into two age groups (40-49 and 50-59) and conducted a statistical analysis of AD and C groups by means of a two tailed t-test. The mean values for TC (DTC), which had been obtained within 3 months before TCF, were significantly different (p < 0.001 95% CI 15.79-48.49) for those in their 40s, but were not different for those in their 50s. In order to check the stability of the data, we analyzed the mean values for DTC and BTC, which had been obtained within 15 months. The results showed the same trend for those in their 40s (p = 0.001 95% CI 10.76-40.87). The mean DTC and BTC values were again not significantly different for those in their 50s. We further divided the subjects into the lower (-181 mg/dl) and higher (209 mg/dl-) DTC values and conducted further statistical analysis with Fisher's exact test. The results were significant in the 40-49 age group (p = 0.004), in the odds ratio (13.75 95% CI 2.32-81.49), but showed no significant difference in the 50-59 age group. The mean LDL-cholesterol values within 3 months before TCF were significantly different in the 40-49 age group (p < 0.001 95% CI 15.22-47.70) and were not different in the 50-59 age group. There was no statistical difference in the mean values for HDL-cholesterol, triglyceride and body mass index in either age group. From these results, it can be concluded that the risk of colorectal adenomatous polyp was associated with a higher serum total cholesterol level in the 40s, and seemed to indicate a close relationship with the risk of colorectal cancer.

Adenomatous Polyps↗

Gravimorphogenesis of Cucurbitaceae plants: development of peg cells and graviperception mechanism in cucumber seedlings.

We examined the effect of microgravity on the peg formation of cucumber seedlings for clarifying the mechanism of gravimorphogenesis in cucurbitaceous plants. The spaceflight experiments verified that gravity controls the formation of peg, hypocotyl hook and growth orientation of cucumber seedlings. Space-grown cucumber developed a peg on each side of the transition zone of the hypocotyl and root, indicating that on the ground peg formation is regulated negatively by gravity (Takahashi et al. 2000). It was found that the auxin-regulated gene, CS-IAA1, was strongly expressed in the transition zone where peg develops (Fujii et al. 2000). In the seedlings grown horizontally on the ground, CS-IAA1 transcripts were much abundant on the lower side of the transition zone, but no such differential expression of CS-IAA1 was observed in the space-grown cucumber (Kamada et al. 2000). These results imply that gravity plays a role in peg formation through auxin redistribution. By the negative control, peg formation on the upper side of the transition zone in the horizontally growing seedlings might be suppressed due to a reduction in auxin concentration. The threshold theory of auxin concentration accounted for the new concept, negative control of morphogenesis by gravity (Kamada et al. 2000). Anatomical studies have shown that there exists the target cells destined to be a peg and distinguishable at the early stage of the growth. Ultra-structural analysis suggested that endoplasmic reticulum develops well in the cells of the future peg. Furthermore, it was found that reorganization of cortical microtubules is required for the change in cell growth polarity in the process of peg formation. The spaceflight experiment with cucumber seedlings also suggested that in microgravity positive hydrotropic response of roots occurred without interference by gravitropic response (Takahashi et al. 1999b). Thus, this spaceflight experiment together with the ground-based studies has shown that cucumber seedling is an ideal for the study of gravimorphogenesis, hydrotropism and their interaction. Although peg formation is seen specifically in cucurbitaceous seedlings, it involves graviperception, auxin transport and redistribution and cytoskeletal modification for controlling cell growth polarity. This system could be a useful model for studying important current issues in plant biology.

Cucumis sativus↗

Hb Tsukumi [beta117(G19)His-->Tyr]: a new hemoglobin variant found in a Japanese male.

We accidentally observed an abnormal elution pattern on high performance liquid chromatogram when we examined the Hb A1c level in a 65-year-old male patient who suffered from pneumoconiosis and alcoholic liver injury. The value of the glycated fraction was within the normal range but the elution patterns on high performance liquid chromatography varied with the glycohemoglobin analyzers. Isoelectrofocusing and urea-cellulose column chromatography showed an anomalous fast-moving beta chain estimated at approximately 47%. The instability test of the hemolysate was slightly positive. Structural analysis demonstrated that the mutant was consisted by a substitution of His-Tyr at beta117. This new variant was named Hb Tsukumi for the place of residence of the patient. Additionally, the nucleotide sequence showed a change of C-->T [CAC (His)-->TAC (Tyr)] at the first base in the 117th codon of the beta gene.

Aged↗

[Influential factors on health-related quality of life after cerebral vascular disease].

A mail survey was conducted to elucidate the influential factors on heath-related quality of life (HRQOL) after cerebral vascular disease. Questionnaires for clinicians and their patients were mailed to 2,587 hospitals with more than 100 beds, which have at least one of the following departments: neurosurgery, neurology, psychiatry or rehabilitation. Each mailing contained a request to the clinician and questionnaires for 5 cases. 378 effective questionnaires could be collected, meaning the collection rate was 2.9%. The questions for the physicians concerned diagnosis (cerebral infarction or hemorrhage), duration of illness, activities of daily living(ADL), manifestation of paralysis and psychiatric symptoms and so forth. The questionnaire for the patients was composed of items from the EuroQol clinical version (EuroQol). Geriatric Depression Scale short form (GDS) and inquiries concerning family living with the patients, their housekeeping and so on. A visual analogue scale (VAS) concerning health state of the EuroQol was used as a measure of HRQOL. Coefficients of determination between VAS and other inquiries were calculated by regression analysis or ANOVA, revealing that "anxiety/depression", "GDS" and 16 other items were statistically significant on VAS (p < 0.05). General linear model (GLM) analysis using VAS as a criterion variable and these 18 items as predictor variables showed that "sleep disturbance" and GDS score were most influential on VAS according to the F value of the type 3 sum of squares. "Health state today compared to that during the past one year", "shopping as housekeeping", "ADL" and "pain/discomfort" also have some influence on VAS. In conclusion, sleep disturbance and depression had the most deleterious effect on HRQOL.

Aged↗

[Congenital thrombophilia caused by protein C deficiency].

To clarify the prevalence of protein C deficiency in patients with cardiovascular problems, we identified 54 patients with protein C deficiency by screening approximately 26,800 patients. The observed prevalence of protein C deficiency was 1 in 500. From the results of genetic analysis of 67 Japanese families with protein C deficiency, the recurrent defects of Phe139Val, Arg169Trp, Val297Met, Met364Ile substitutions and a G8857 deletion were accounting 49% of Japanese families with protein C deficiency. The defects including Phe139Val and Met364Ile substitutions and a G8857 deletion were only found in Japanese subjects and seemed to be a founder effect. Protein C deficiency is associated with a predisposition to venous thrombosis. It is not clear whether the deficiency is involved in arterial occlusion. We identified 34 patients with protein C deficiency manifested 45 episodes of arterial occlusive disease. We compared the onset age of arterial occlusive disease between patients with protein C deficiency and a group of patients with normal protein C levels. We found the early onset of acute myocardial infarction and atherothrombotic cerebral infarction in patients with protein C deficiency. Thus, our study suggests that congenital protein C deficiency contributes to earlier onset of arterial occlusive diseases in Japanese subjects.

Arterial Occlusive Diseases↗

Scanning gene expression during neuronal cell death evoked by nerve growth factor depletion.

Depletion of nerve growth factor (NGF) from differentiated, neuronal PC12 cells causes a form of programmed cell death that stems from the attenuation of NGF receptor signaling and the resultant expression of certain genes required for cell death. To better understand the associated molecular events, we surveyed the changes in gene expression in PC6-3 cells, a subline of PC12, caused by depletion of NGF. Using restriction landmark cDNA scanning, we assessed the expression patterns of as many as 15,000 gene species, and 30 genes were isolated whose expression was altered in the absence of NGF. Of the 20 genes up-regulated in the absence of NGF, including transcription factor LRF-1/ATF3, most were also up-regulated during the programmed death of cortical neurons caused by Ca2+ ionophore. Their function may thus be a general feature of programmed neuronal cell death. In contrast, with one exception, expression of down-regulated genes was NGF-dependent and therefore diminished in the absence of NGF but unaffected by Ca2+ ionophore. These findings confirm that global investigation of the features of up- and down-regulated genes should add substantially to our understanding of the regulation of programmed neuronal cell death and the mechanisms involved.

Animals↗

Effect of Hochu-ekki-to (TJ-41), a Japanese herbal medicine, on the survival of mice infected with influenza virus.

The antiviral effect of Hochu-ekki-to (TJ-41), a Japanese herbal medicine, was investigated using mice infected with influenza virus. TJ-41 was found to increase the survival rate, prolong the mean survival days, suppress viral growth in bronchoalveolar labage fluid (BALF) and inhibit the lung index (lung consolidation) on day 4 after infection in mice infected with influenza, after the agent had been administered orally once daily from day 7 to 2 before infection and from day 0 to 4 after infection. Administration of TJ-41 decreased the BALF concentrations of IL-1alpha, IL-6 and GM-CSF, but not TNF-alpha or interferon-gamma (IFN-gamma), on day 4 after infection. In addition, TJ-41 elevated the level of IFN-alpha in BALF on day 2 after infection. Yet, TJ-41 did not show any inhibitory effect on the growth of influenza virus in vitro. These results suggest that TJ-41 exerts its inhibitory effect on influenza virus infection via enhancement of the host immune responses in this experimental murine system.

Administration, Oral↗

New rapid flow cytometric method for the enumeration of nucleated red blood cells.

BACKGROUND: Nucleated red blood cells (NRBC) in blood specimens compromise the automated white blood cell (WBC) count on most hematology analyzers. This makes it necessary to correct the WBC count by subtracting separately counted NRBC by manual microscopy. In addition, it is clinically important to establish the non-physiological presence of NRBC in blood specimens because of their association with significant hematological and non-hematological disease. Unfortunately, manual microscopic methods lack sensitivity, specificity and reproducibility required for both. METHODS: We have developed a new, rapid flow cytometric method for the detection and enumeration of NRBC, based on two-color staining with anti-CD45-fluorescein-isothiocyanate (CD45-FITC) and propidium iodide (PI). EDTA anticoagulated blood samples are incubated for 30 min with CD45-FITC, followed by 30 sec acid-hypotonic lysis, containing PI and subsequent addition of an alkaline-hypertonic solution. The samples are thus ready for flow cytometric analysis. RESULTS: The method typically yields up to four populations, (1) red blood cell (RBC) ghosts, debris, lyse-resistant RBC, reticulocytes and platelets, (2) CD45(+) WBC unstained by PI, (3) CD45(+) WBC stained by PI, and (4) CD45(-)/PI(bright) NRBC. Manual microscopic reference NRBC counts of 25 patient specimens showed excellent correlation with flow cytometric NRBC determinations (y = 0.943x+0. 66; r(2) = 0.982). Performance for precision showed a mean coefficient of variation (CV) for the flow cytometric method of =10%, with a mean CV for manual NRBC counts of 40%. CONCLUSIONS: We conclude that this method is suitable for NRBC counting in peripheral blood specimens with improved performance in terms of accuracy, reproducibility when compared to manual microscopic methods.

Adult↗

Characterization of orexin-A and orexin-B in the microdissected rat brain nuclei and their contents in two obese rat models.

Orexin-A and orexin-B (also known as hypocretins) are newly discovered hypothalamic peptides that stimulate food intake. Using separate radioimmunoassays for these rat orexins, we determined their distributions in microdissected nuclei of the diencephalon and brainstem which have accumulations of orexin fibers. High orexin contents (orexin-A: between 250 and 350 fmol/mg protein and orexin-B: between 650 and 900 fmol/mg protein) were present in the lateral hypothalamus; ventromedial hypothalamic, paraventricular thalamic and dorsal raphe nuclei; periaqueductal central gray and locus coeruleus. Moderate orexin contents (orexin-A: between 100 and 250 fmol/mg protein and orexin-B: between 300 and 500 fmol/mg protein) were found in the median eminence; suprachiasmatic, paraventricular hypothalamic, arcuate and supraoptic nuclei; substantia nigra and the nucleus of the solitary tract. Mature orexin-A and -B peptides were the major endogenous orexin molecules in these nuclei. The orexin-A and -B contents in the brains of obese Zucker rats that have disrupted leptin receptor were significantly higher than in their lean littermates, but in Otsuka Long-Evans Tokushima Fatty rats that have disrupted cholecystokinin type-A receptor the contents were similar to those of the controls. The widespread orexin distributions in the nuclei of diencephalon and brainstem suggest that orexins serve as neuromodulators, neurotransmitters, or both, in a wide variety of neural networks that regulate the autonomic and neuroendocrine systems.

Animals↗

Up-regulation of uterine UCP2 and UCP3 in pregnant rats.

Pregnancy produces profound changes in hormone dynamics, thermoregulation and energy metabolism. Uncoupling proteins (UCPs) have been identified in a variety of tissues and UCP1 is known to play important roles in energy homeostasis, while the regulation of UCP2 and UCP3 is still unclear. The present study aimed to investigate the effects of the changes during pregnancy on UCP gene expression in the uterus, as well as in brown adipose tissue (BAT), white adipose tissue (WAT), soleus muscle (Muscle), and liver, throughout the estrus and metestrus periods, at early, middle and late stages in pregnancy, and during post-gestational stages. The expression of uterine UCP2 and UCP3 were up-regulated by 3.2- and 1. 5-fold, respectively, during the late stage of pregnancy with an increase of WAT leptin mRNA expression and exogenous administration of leptin resulted in induction of the uterine UCP2 and UCP3 levels. Contrary to uterine UCPs, UCP1 mRNA expression in BAT was down-regulated by 0.5-fold and there were no remarkable changes in WAT or liver UCP2, or Muscle UCP3 expression throughout the periods. These results indicate that UCP gene expressions during pregnancy are regulated tissue-dependently, and up-regulation of uterine UCP2 and UCP3 mRNA may be due to increased leptin levels.

Adipose Tissue↗

TrkB mutant lacking the amino-terminal half of the extracellular portion acts as a functional brain-derived neurotrophic factor receptor.

A series of mutants with deletion in the extracellular portion of TrkB were expressed transiently and stably in mammalian cells to examine the brain-derived neurotrophic factor (BDNF)-binding properties of TrkB. We found that these binding activities were retained by the TrkB deletion mutant (TrkBDelta4) lacking most of the extracellular portion, cysteine-rich cluster 1 and 2, leucine-rich motif and most of the first immunoglobulin-like domain (Ig1). Furthermore, the results of the neurotrophin selectivity, the equilibrium binding constant, auto-phosphorylation and BDNF dependent cell survival indicate that TrkBDelta4 acts as a functional BDNF receptor comparable to wild-type TrkB. Thus, our findings showed that only the carboxyl-terminal half of the extracellular portion of TrkB, which includes the Ig2 domain, is essential for the functional BDNF receptor.

3T3 Cells↗

Ca2(+)-dependent interaction of N-copine, a member of the two C2 domain protein family, with OS-9, the product of a gene frequently amplified in osteosarcoma.

N-copine is a novel two C2 domain protein that shows Ca2(+)-dependent phospholipid binding and membrane association. By using yeast two-hybrid assays, we identified OS-9 as a protein capable of interacting with N-copine. We further revealed that the second C2 domain of N-copine bound with the carboxy-terminal region of OS-9. Their interaction in vivo was also confirmed by co-immunoprecipitation from 293E cells co-expressing transfected N-copine and OS-9. In vitro binding assays showed that this interaction was Ca2(+)-dependent. By Northern blot analysis, N-copine and OS-9 were co-expressed in the same regions of human brain. These results reveal that OS-9 is a potential target of N-copine.

Binding Sites↗

Identification of a novel kinase-like gene induced during neuronal cell death.

When deprived of neurotrophic factors, neuronal cells undergo a form of programmed cell death that involves a cascade of gene expression. To better understand this cascade, we screened the genes induced during programmed cell death evoked in neuronal PC6-3 cells by NGF-depletion and discovered a novel gene, NIPK (Neuronal cell death Inducible Putative Kinase), that contains a kinase-like domain. Expression of NIPK was also induced in cultured sympathetic neurons by NGF deprivation and in cortical neurons exposed to the Ca2+ ionophore, A23187. In contrast, NIPK was not induced during non-neuronal cell death evoked by serum or growth factor deprivation, or by treatment with methyl methanesulfonate, an agent that causes cell death by damaging DNA. Taken together, these findings suggest that NIPK is involved in programmed cell death via a pathway that is present in neurons but is absent in non-neurons.

Amino Acid Sequence↗