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T Moriya

Publications and source records attributed to T Moriya.

At least 37 records · Page 2Linked to original sources

Night-time restricted feeding normalises clock genes and Pai-1 gene expression in the db/db mouse liver.

AIMS/HYPOTHESIS: An increase in PAI-1 activity is thought to be a key factor underlying myocardial infarction. Mouse Pai-1 (mPai-1) activity shows a daily rhythm in vivo, and its transcription seems to be controlled not only by clock genes but also by humoral factors such as insulin and triglycerides. Thus, we investigated daily clock genes and mPai-1 mRNA expression in the liver of db/db mice exhibiting high levels of glucose, insulin and triglycerides. METHODS: Locomotor activity was measured using an infrared detection system. RT-PCR or in situ hybridisation methods were applied to measure gene expression. Humoral factors were measured using measurement kits. RESULTS: The db/ db mice showed attenuated locomotor activity rhythms. The rhythmic expression of mPer2 mRNA was severely diminished and the phase of mBmal1 oscillation was advanced in the db/db mouse liver, whereas mPai-1 mRNA was highly and constitutively expressed. Night-time restricted feeding led to a recovery not only from the diminished locomotor activity, but also from the diminished Per2 and advanced mBmal1 mRNA rhythms. Expression of mPai-1 mRNA in db/db mice was reduced to levels far below normal. Pioglitazone treatment slightly normalised glucose and insulin levels, with a slight reduction in mPai-1 gene expression. CONCLUSIONS/INTERPRETATION: We demonstrated that Type 2 diabetes impairs the oscillation of the peripheral oscillator. Night-time restricted feeding rather than pioglitazone injection led to a recovery from the diminished locomotor activity, and altered oscillation of the peripheral clock and mPai-1 mRNA rhythm. Thus, we conclude that scheduled restricted food intake may be a useful form of treatment for diabetes.

Animals↗

Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer.

Oestrogen receptor-binding fragment associated gene 9, EBAG9, is an oestrogen-responsive gene that was identified in MCF-7 human breast carcinoma cell line. It is identical to RCAS 1, a cancer cell surface antigen possibly involved in immune escape. In the present study, we examined the expression of EBAG9/RCAS1 in human epithelial ovarian cancer using immunohistochemistry, immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR). A total of 90 epithelial ovarian cancer cases were examined immunohistochemically by means of the antibodies for EBAG9 and ERalpha. The correlation between EBAG9 immunoreactivity and clinicopathological parameters was examined. mRNA expression of EBAG9 and ERalpha were evaluated by RT-PCR in 22 cases. The expression for EBAG9 and ERalpha was examined by immunoblotting in 12 ovarian cancer cell lines. EBAG9 immunoreactivity was detected in the surface and cytoplasm of carcinoma cells in 46 out of 90 cases (51.1%). EBAG9 expression was significantly higher in serous histology (P=0.0402) and advanced disease (P=0.0206). No significant relationship was detected between EBAG9 immunoreactivity and overall survival (P=0.689). There was a highly significant correlation between EBAG9 and ER immunoreactivity (P<0.0001). The EBAG9 mRNA was detected in 20 out of 22 cases. In all of the cases that were positive for ERalpha mRNA, they were also positive for EBAG9 mRNA. Immunoreactive band corresponding to EBAG9 was detected in 11 out of 12 of ovarian cancer cell lines, and was consistent with ERalpha expression. In conclusion, the wide distribution of EBAG9 and its relation to advanced disease suggest that this protein may play important roles in epithelial ovarian cancer.

Antigens, Neoplasm↗

Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer.

Cancer chemotherapy for haemodialysis patients has never been established. To elucidate the feasibility of cisplatin-based combination chemotherapy for haemodialysis patients with lung cancer, a dose escalation study was conducted. Five haemodialysis patients with lung cancer were treated with cisplatin and etoposide. A starting dose of 40 mg m(-2) of cisplatin on day 1 and 50 mg m(-2) of etoposide on days 1, 3 and 5 were administered as the first course for the first patient. Membrane haemodialysis was regularly performed three times a week and soon after the completion of therapy. By monitoring toxicity and pharmacokinetics data, the dose was escalated course by course and patient by patient. Dose escalation was completed for the first two patients resulting in full-dose chemotherapy consisting of 80 mg m(-2) of cisplatin on day 1 and 100 mg m(-2) of etoposide on days 1, 3 and 5. Multiple courses of the full-dose chemotherapy were administered to the other three patients. Toxicity was manageable and tolerable for all. Pharmacokinetics data were comparable to those from patients with normal renal function, except for potential long-lasting higher levels of free platinum in the renal insufficiency group. In conclusion, this standard-dose combination chemotherapy was feasible even for haemodialysis patients.

Aged↗

Relation between brain oxygen metabolism and temperature gradient between brain and bladder.

Brain temperature is slightly higher than systemic core temperature normally. Fluctuations of a temperature gradient between brain and core body have recently been reported after a severe brain insult. The pathophysiological significance of the gradient fluctuations is unclear. This study aims to identify the gradient fluctuations between brain and core temperatures after a brain insult. Temperature gradient (brain temperature minus bladder temperature: degrees C) was measured in 11 patients (125 points) with severe brain injury (4 patients with subarachnoid hemorrhage, 4 with cerebral hemorrhage. and 3 with traumatic brain injury). Cerebral perfusion pressure (CPP; mmHg) and jugular venous blood saturation (SjO2; %) was also measured. The average gradient was 0.29 +/- 0.285 degrees C when CPP was above 50 mmHg. SjO2 was inversely related to the temperature gradient in a significant manner (r = 0.472; P < 0.0001). Temperature gradients tended to increase and then decrease when CPP < 50 mmHg. This study demonstrates that increased temperature gradient has a significant inverse correlation with SjO2 at CPP > 50 mmHg. The current results suggest that the fluctuations in temperature gradient in critical conditions reflect brain ischemia.

Adult↗

Importance of hemodynamics management in patients with severe head injury and during hypothermia.

OBJECTIVE: To evaluate the hemodynamics in patients with traumatic brain injury (TBI) during therapeutic hypothermia. METHODS: Subjects were 25 patients with TBI (GCS; 8 or less). Mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), cardiac index (CI), systemic oxygen delivery (DO2), systemic vascular resistance index (SVRI), and pulmonary capillary wedge pressure (PCWP) were measured. Patients were retrospectively divided into 3 groups: normothermia (n = 5; NT), and survivors (n = 14; HT-S) and non-survivors (n = 6; HT-Non-S) after hypothermia. and hemodynamics were investigated for difference among groups at 24 hours from induction of normothermia or hypothermia. RESULTS: CPP target was above 70 mmHg, however, HT-Non-S could not maintain CPP above 70 mmHg. The low CPP was the result of elevated ICP, low MAP (P < .05), or both during hypothermia. In HT-Non-S, significantly high SVRI and low CI (P < .05) causing dehydration were observed during cooling. DO2 could not be maintained in HT-Non-S during hypothermia. CONCLUSIONS: These results suggest that patients run the risk of impairing hemodynamics during therapeutic hypothermia. Hemodynamic management is essential during hypothermia. If dehydration occurs during hypothermia. MAP may be reduced due to inadequate sedation, analgesia, and excess use of diuretic agents.

Blood Pressure↗

Changes in cerebrovascular response during brain hypothermia after traumatic brain injury.

OBJECTIVE: Transcranial Doppler sonography (TCD) provides a rapid and noninvasive assessment of cerebral hemodynamics after traumatic brain injury. This study evaluates the change of cerebrovascular response at the rewarming stage of brain hypothermia using TCD. MATERIAL AND METHODS: Seventeen patients who had suffered from closed brain injury were investigated with daily TCD recordings and the changes in flow velocities were evaluated to determine whether they reflected the temperature during brain hypothermia. All patients who had treated brain hypothermia underwent continuous monitoring of SjO2, mean arterial blood pressure, and intracranial pressure (ICP). RESULTS: No significant changes in ICP and cerebral perfusion pressure (CPP) were recorded in all cases. Of 17 patients, 5 had a significant increase in SjO2 > 75% or more, retrospectively, with a robust increase in flow velocities of the middle cerebral artery (P < .01) at the rewarming stage. These cases marked a decrease in pulsatility index (P < .05) concomitant with an increase in SjO2 values. The CT scan revealed acute brain swelling in these cases. CONCLUSION: These data suggest cerebral vasoactivity could be altered at the rewarming stage. Hypothermia runs a risk of hyperemia at the rewarming stage, which induced a decrease in cerebral vasoresistance.

Acute Disease↗

Constant light housing attenuates circadian rhythms of mPer2 mRNA and mPER2 protein expression in the suprachiasmatic nucleus of mice.

Constant light (LL) or constant dark (DD) environmental lighting conditions cause a free-running period and activity reduction in the rodent behavioral circadian rhythm. In order to understand the molecular process underlying behavioral rhythms in LL or DD housing conditions, we examined the circadian profile of mPer2 mRNA and mPER2 in the suprachiasmatic nucleus (SCN), a main oscillator, of free-running mice. The circadian expression rhythm of mPer2 in the SCN was dampened under 7-day LL conditions, whereas that of mPER2 protein was moderately attenuated and its expression peak delayed. The circadian expression of mPer2 and its product was slightly attenuated and advanced by 7-day DD conditions. With arrhythmic behavioral activity caused by long-term LL housing, mPER2 protein lost its rhythmicity in the SCN. On the other hand, LL or DD housing did not affect the mPer2 gene and its product in the cerebral cortex. The present results suggest that mPER2 circadian expression in the SCN corresponds well with behavioral circadian oscillation under LL or DD conditions. Thus, the behavioral circadian rhythm seems to correlate with molecular clock works in the SCN.

Analysis of Variance↗

Pituitary adenylate cyclase-activating polypeptide produces a phase shift associated with induction of mPer expression in the mouse suprachiasmatic nucleus.

The main mammalian circadian pacemaker is located in the suprachiasmatic nucleus of the hypothalamus. Clock genes such as the mouse Period gene (mPer) play a role in this core clock mechanism in the mouse. With brief light exposure during the subjective night, the photic information, which is conveyed directly to the suprachiasmatic nucleus via the retinohypothalamic tract, results in mPer1 and mPer2 expression in the suprachiasmatic nucleus. Glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP) are co-stored in the retinohypothalamic tract. Recent studies have suggested that not only glutamate but also PACAP are key players in the phase shift that occurs during subject night; however, research demonstrating a direct association between the PACAP-induced phase shift and mPer gene expression has yet to be conducted. In the present study, PACAP (200 pmol) injected into the lateral ventricle during subjective night (circadian time 16; circadian time 12, onset of locomotor activity) caused a moderate phase delay associated with moderate expression of mPer1 and only slight expression of mPer2 in the mouse suprachiasmatic nucleus. PACAP-induced mPer1 expression was also observed in the paraventricular nucleus and periventricular area of the hypothalamus. (+)MK-801 (0.5 mg/kg), an N-methyl-D-aspartate (NMDA) receptor antagonist, suppressed both the PACAP-induced phase delay and mPer1 expression. From these results we suggest that PACAP induces phase delays in the mouse circadian rhythm in association with an increase of mPer expression in the suprachiasmatic nucleus via the activation of NMDA receptors.

Animals↗

Fluctuation of serum HCV-RNA levels in untreated blood donors with chronic hepatitis C virus infection.

The hepatitis C virus (HCV)-RNA levels were measured in 281 serum samples from 32 untreated volunteer blood donors prospectively collected over a period of 14-73 months. The HCV-RNA levels were tested by the branched DNA signal amplification assay. The mean HCV-RNA levels of each donor ranged from 4.92 log10-6.36 log10 gene equivalents/mL (25%, median, 75% percentile; 5.51, 5.79, 6.12 log10 gene equivalents/mL). The fluctuations of HCV-RNA levels in individuals, represented by the ratio of the maximum value divided by the minimum value, ranged from a 1.7- to a 141-fold change. Fluctuations with more than a 10-fold change were observed in five subjects: 11-, 15-, 17-, 96- and 141-fold changes. Eleven subjects were followed for at least 5 years; all subjects had fluctuations of HCV-RNA levels greater than 3-fold during the observation period. No blood donor was observed whose HCV levels changed from a high-level phase to a low-level phase or from low to high. No subjects cleared HCV during follow-up, although two had undetectable HCV-RNA levels transiently. These findings reveal that changes in HCV-RNA levels occur which are unrelated to treatment with interferon and ribavirin.

Female↗

Comparison of the histological and histochemical properties of skeletal muscles between carbon dioxide and electrically stunned chickens.

1. Histological and histochemical profiles of Musculus pectoralis (PT, type IIB fibres), M. iliotibialis lateralis (ITL, types IIA + IIB fibres) and M. puboischiofemoralis pars medialis (PIF, type I fibres) were compared in carbon dioxide (37%, 70 s) and electrically (14 V, 5 s) stunned male chickens. 2. Muscle materials were taken at 0, 4 and 24 h from carcases dressed and cooled with ice-water mixture for 30 min. Glycogen and fat contents, and adenosine triphosphatase and reduced nicotinamide adenine dinucleotide dehydrogenase activities of fibres were measured. 3. In PT muscle at 0 h, gas stunned chickens showed many fibres with high glycogen content but those electrically stunned contained few such fibres. Fibres from gas stunned birds had lost almost all their glycogen after 24 h of cold storage. 4. In the ITL muscle of gas stunned chickens at 0 h residual glycogen was observed in type IIB fibres. In contrast, in the electrically stunned birds it was in type IIA, showing the different effects of the stunning methods. During cold storage, glycogen disappeared earlier in type IIB than IIA fibres. 5. In PIF muscle with fibres of low glycogen content, the gas stunned chickens maintained a good fibre structure for 4 h or more, but the electrically stunned had already lost intact fibre structure at 4 h. 6. These results indicated that the carbon dioxide stunning was a better method for chicken welfare and meat quality than electrical stunning.

Adenosine Triphosphatases↗

Effects of insulin-like growth factor on nitrogen balance during hypoxic exposure.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) accompanied with hypoxaemia may induce net protein catabolism and hypoxaemia could be an important trigger of a systemic catabolic response. The aim of this study was to examine the anabolic effects of recombinant human insulin-like growth factor-I (IGF-1) in rats exposed to hypoxia. Although acute hypoxia is usually accompanied with a decrease in dietary intake, the usual nitrogen intake was maintained in this study. Sprague-Dawley rats were maintained by continuous infusion of solution for total parenteral nutrition for 6 days. The animals were then randomly assigned to a normoxic (N) or a hypoxic (H) group. During the last 3 days of the experiment N and H rats were randomised to receive either IGF-I or vehicle. Exposure to hypoxia caused a decrease in body-weight gain accompanied by a negative nitrogen balance, which was mainly due to increased urinary nitrogen excretion. No effect of recombinant human IGF-I treatment on body weight was observed during exposure to hypoxia, although nitrogen balance normalised. The co-infusion of recombinant human insulin-like growth factor-1 and total parenteral nutrition has a significant net anabolic effect, as demonstrated by nitrogen retention and reduction in urine protein excretion observed in rats. Insulin-like growth factor-1 may help to ameliorate the protein catabolism observed under hypoxic conditions.

Animals↗

[Assessment of mode of recurrence after surgical treatment for thymic carcinoma].

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.

Adult↗

Circadian profile of Per gene mRNA expression in the suprachiasmatic nucleus, paraventricular nucleus, and pineal body of aged rats.

Aging alters circadian components such as the free-running period, the day-to-night activity ratio and photic entrainment in behavioral rhythms, and 2-deoxyglucose uptakes and neuronal firing in the suprachiasmatic nucleus (SCN). A core clock mechanism in the mouse SCN appears to involve a transcriptional feedback loop in which Period (Per) and Cryptochrome (Cry) genes play a role in negative feedback. The circadian rhythm systems include photic entrainment, clock oscillation, and outputs of clock information such as melatonin production. In this experiment, we examined clock gene expression to determine whether circadian input, oscillation, and output are disrupted with aging. Circadian expression profiles of rPer1, rPer2, or rCry1 mRNA were very similar in the SCN, the paraventricular nucleus of the hypothalamus (PVN), and the pineal body of young and aged (22-26 months) rats. On the other hand, the photic stimulation-induced rapid expression of Per1 and Per2 in the SCN was reduced with aging. The present results suggest that the molecular mechanism of clock oscillation in the SCN, PVN, and pineal body is preserved against aging, whereas the impairment of Per1 induction in the SCN after light stimulation may result in impaired behavioral photic entrainment in aged rats.

Aging↗

EBAG9/RCAS1 in human breast carcinoma: a possible factor in endocrine-immune interactions.

EBAG9 has been recently identified as an oestrogen responsive gene in MCF-7 human breast carcinoma cells. EBAG9 is identical to RCAS1, a cancer cell surface antigen possibly involved in immune escape. In this study, we examined the expression of EBAG9/RCAS1 in human breast carcinomas using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). EBAG9 immunoreactivity was also associated with various clinicopathological parameters, including intratumoural infiltration of inflammatory cells, to examine the biological significance of EBAG9 in human breast carcinomas. EBAG9 immunoreactivity was detected in the entire surface and cytoplasm of carcinoma cells in 82 out of 91 invasive ductal carcinomas (90.1%). In non-neoplastic mammary glands, EBAG9 immunoreactivity was weakly present on the luminal surface of epithelial cells. Results from RT-PCR (n = 7) were consistent with those of immunohistochemistry. EBAG9 immunoreactivity was significantly associated with estrogen receptor (ER) alpha labelling index (P = 0.0081), and inversely associated with the degree of intratumoural infiltration of mononuclear cells (P = 0.0020), or CD3(+) T lymphocytes (P = 0.0025). This study suggests that EBAG9 is produced via ER in carcinoma cells and inhibits the intratumoural infiltration of T lymphocytes in the context of a possible endocrine-immune interaction in human breast carcinomas.

Adult↗

Activation during endogenous orienting of visual attention using symbolic pointers in the human parietal and frontal cortices: a functional magnetic resonance imaging study.

Brain activation induced by endogenous orienting with a motor response was investigated by functional magnetic resonance imaging. We conducted four cued-attention experiments in which peripheral attention was caused by one of three symbolic pointers (eyes, squares as artificial eyes, or an arrow) that was predictive or not predictive of the target location. Attentional shift caused by the predictive and non-predictive cues induced right and left parietal activation across cue modalities, respectively. Regardless of the predictability of the target location, the eyes and arrow induced left parietal and frontal activation, and the arrow induced left parietal activation more than the squares. These results suggested that the left parieto-frontal network was involved in motor attention caused by natural or familiar pointers, whereas the right parietal cortex was involved in endogenous orienting.

Adult↗

Visualization of mPer1 transcription in vitro: NMDA induces a rapid phase shift of mPer1 gene in cultured SCN.

Many physiological and behavioral phenomena are controlled by an internal, self-sustaining oscillator with a periodicity of approximately 24 hr. In mammals, the principal oscillator resides in the suprachiasmatic nucleus (SCN). A light pulse during the subjective night causes a phase shift of the circadian rhythm via direct glutamatergic retinal afferents to the SCN [1]. Along with the accepted theoretical models of the clock, it is suggested that behavioral resetting of mammals is completed within 2 hr [2]; however, the molecular mechanism has not been elucidated. Here, we show the real-time image of the transcription of the circadian-clock gene mPer1 in the cultured SCN by using the transgenic mice that carry a luciferase reporter gene under the control of the mPer1 promoter [3]. The real-time image demonstrates that the mPer1 promoter activity oscillates robustly in a circadian manner and that this promoter activity is reset rapidly (within 2-3 hr) when a phase shift occurs.

2-Amino-5-phosphonovalerate↗

Ideographic characters call for extra processing to correspond with phonemes.

Cortical areas used in the copying of Japanese ideographic characters and syllabic characters were studied using functional magnetic resonance imaging in healthy volunteers. Complexity of characters was controlled to illustrate differences resulting from character to sound conversion differences between the ideographic and syllabic characters. Statistical comparisons indicated extensive activation in the fusiform gyrus, posterior portions around the intraparietal sulcus and in the conjunction area of BA 6, 9 and 44 (which is assumed to be Exner's area) during the copying of ideographic characters. These findings suggested that indirectness between ideographic characters and their pronunciation demands extra processing such as semantic mediation and intensive grapheme processing in comparison with syllabic characters.

Adult↗