An analytical representation of raindrop size distribution in a mixed convective and stratiform precipitating system as revealed by field observations

This study investigated a rainfall event under a typhoon influence using a 2D video disdrometer and weather radar observations to characterize raindrop size distribution (DSD) in a mixed convective and stratiform precipitating system. During the time period when both convective and stratiform rainfalls existed, the DSDs generally indicated a monotonically decreasing shape with increasing particle size, with a relatively gradual decrease at intermediate particle size observed at certain times; this feature is attributed to the combined effect of convective and stratiform rainfalls. During the transitional period between convective and stratiform rainfalls, the DSDs exhibited a bimodal shape. The DSDs were well approximated by a newly proposed gamma raindrop distribution combined with exponential (GRACE) distribution function, which was defined as the sum of the exponential distribution and the gamma distribution. A comparison of the volume ratio of the exponential and gamma components of the GRACE distribution revealed that the exponential component of the DSD was larger than the gamma component in the bimodal DSD. These results suggest that the DSD became bimodal during the period when stratiform rainfall predominated because of the weakening of convective rainfall. The GRACE distribution is useful for understanding cloud-microphysical processes in mixed stratiform and convective precipitation conditions

Proliferation and cell death of human glioblastoma cells after carbon-ion beam exposure: Morphologic and morphometric analyses

Histological analyses of glioblastoma cells after carbon-ion exposure are still limited and ultrastructural characteristics have not been investigated in detail. Here we report the results of morphological and morphometric analyses of a human glioblastoma cell line, CGNH-89, after ionizing radiation to characterize the effect of a carbon-beam on glioblastoma cells. Using CGNH-89 cells exposed to 0–10 Gy of X-ray (140kVp) or carbon-ions (18.3 MeV/nucleon, LET = 108 keV/μm), we performed conventional histology and immunocytochemistry with MIB-1 antibody, transmission electron microscopy, and computer-assisted, nuclear size measurements. CGNH-89 cells with a G to A transition in codon 280 in exon 8 of the TP53 gene had nuclei with pleomorphism, marked nuclear atypia and brisk mitotic activity. After carbon-ion and X-ray exposure, living cells showed decreased cell number, nuclear condensation, increased atypical mitotic figures, and a tendency of cytoplasmic enlargement at the level of light microscopy. The deviation of the nuclear area size increased during 48 hours after irradiation, while the small cell fraction increased in 336 hours. In glioblastoma cells of the control, 5 Gy carbon-beam, and 10 Gy carbon-beam, and MIB-1 labeling index decreased in 24 hours (12%, 11%, 7%, respectively) but increased in 48 hours (10%, 20%, 21%, respectively). Ultrastructurally, cellular enlargement seemed to depend on vacuolation, swelling of mitochondria, and increase of cellular organelles, such as the cytoskeleton and secondary lysosome. We could not observe apoptotic bodies in the CGNH-89 cells under any conditions. We conclude that carbon-ion irradiation induced cell death and senescence in a glioblastoma cell line with mutant TP53. Our results indicated that the increase of large cells with enlarged and bizarre nuclei, swollen mitochondria, and secondary lysosome occurred in glioblastoma cells after carbon-beam exposure.学位記番号：医博甲1096, 学位の種類：博士（医）, 学位授与年月日：平成20年3月25

Effect of vasopressin V1- and V2-receptor stimulation on blood pressure in DOCA-salt hypertensive rats.

We recently reported that stimulation of the arginine vasopressin (AVP) V1-receptor enhanced the pressor response in spontaneously hypertensive rats (SHR). In the present study, we investigated acute changes in systolic blood pressure (SBP) and heart rate (HR) after intravenous injections of AVP, OPC-21268 (a V1-receptor antagonist), and OPC-31260 (a V2-receptor antagonist), in anesthetized DOCA-salt hypertensive rats (DOCA) and age-matched sham-operated Wistar rats (control) to determine whether the pressor effect is specific to SHR or is present in other hypertensive animal models. SBP increased significantly in DOCA rats 9 min after injection of AVP 5 ng/kg without a concomitant increase in HR. Neither OPC-21268 3mg/kg nor OPC-31260 3mg/kg caused significant changes in SBP or HR. SBP tended to increase when AVP was administered after injection of OPC-31260. HR increased significantly 15 min after the combined treatment with OPC-31260 and AVP in DOCA rats compared with control rats. SBP did not change significantly when AVP was administered after injection of OPC-21268 in DOCA or control rats, but HR decreased significantly from 1 to 4 min after injection of AVP in DOCA rats. Our results suggest that V1-receptor stimulation does not enhance the pressor response in the DOCA rat, which is a model of volume-dependent hypertension, suggesting that the AVP system, especially V1-receptor, is not as important in the development or maintenance of hypertension in DOCA rats as in SHR.</p

Enhanced pressor response in spontaneously hypertensive rats induced by stimulation of vasopressin-V1 receptors.

To elucidate the effect of the arginine vasopressin (AVP) system in vivo, especially V1 and V2 activity, on blood pressure, we measured the acute changes in blood pressure and heart rate after AVP, OPC-21,268 (a V1 receptor antagonist), and OPC-31,260 (a V2 receptor antagonist) were injected intravenously in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at the age of 15 weeks. Compared with the control period, single injection of AVP 5 ng/kg significantly increased systolic blood pressure in WKY rats without a concomitant increase in heart rate, but there was no significant increase in blood pressure in SHR. In contrast, single injection of either OPC-21,268 3 mg/kg or OPC-31,260 3 mg/kg did not affect blood pressure or heart rate in either SHR or WKY rats. Injection of AVP after the administration of OPC-31,260 induced a greater increase in blood pressure in SHR than in WKY rats, whereas injection of AVP after the administration of OPC-21,268 did not induce any clear increase in blood pressure in SHR or WKY rats. These results suggest that SHR have enhanced pressor activity mediated by V1 receptors and that this increase may be due to an increase in their number. In conclusion, enhancement of V1 activity may contribute to the development of high blood pressure in SHR.</p

Preoperative prognostic nutritional index predicts postoperative infectious complications and oncological outcomes after hepatectomy in intrahepatic cholangiocarcinoma

Background: In the surgical treatment of intrahepatic cholangiocarcinoma (ICC), postoperative complications may be predictive of long-term survival. This study aimed to identify an immune-nutritional index (INI) that can be used for preoperative prediction of complications. Patients and methods: Multi-institutional data from 316 patients with ICC who had undergone surgical resection were retrospectively analysed, with a focus on various preoperative INIs. Results: Severe complications (Clavien-Dindo grade III-V) were identified in 66 patients (20.8%), including Grade V complications in 7 patients (2.2%). Comparison of areas under the receiver operating characteristic curve (AUCs) among various INIs identified the prognostic nutritional index (PNI) as offering the highest predictive value for severe complications (AUC = 0.609, cut-off = 50, P = 0.008). Multivariate analysis revealed PNI = 50, n = 142) and a low-PNI group (PNI Conclusion: Preoperative PNI appears useful as an INI correlating with postoperative severe complications and as a prognostic indicator for ICC

Efficacy of surgical management for recurrent intrahepatic cholangiocarcinoma: A multi-institutional study by the Okayama Study Group of HBP surgery

Background The prognosis of intrahepatic cholangiocarcinoma (ICC) has been poor, because of the high recurrence rate even after curative surgery. This study aimed to evaluate the prognostic impact of surgical resection of recurrent ICC. Patients and methods A total of 345 cases of ICC who underwent hepatectomy with curative intent in 17 institutions were retrospectively analyzed, focusing on recurrence patterns and treatment modalities for recurrent ICC. Results Median survival time and overall 5-year recurrence-free survival rate were 17.8 months and 28.5%, respectively. Recurrences (n = 223) were classified as early (recurrence at 1 year, n = 92). Median survival time was poorer for early recurrence (16.3 months) than for late recurrence (47.7 months,p<0.0001). Treatment modalities for recurrence comprised surgical resection (n = 28), non-surgical treatment (n = 134), and best supportive care (BSC) (n = 61). Median and overall 1-/5-year survival rates after recurrence were 39.5 months and 84.6%/36.3% for surgical resection, 14.3 months and 62.5%/2.9% for non-surgical treatment, and 3 months and 4.8%/0% for BSC, respectively (p<0.0001). Multivariate analysis identified early recurrence, simultaneous intra- and extrahepatic recurrence, and surgical resection of recurrence as significant prognostic factors. In subgroup analyses, surgical resection may have positive prognostic impacts on intra- and extrahepatic recurrences, and even on early recurrence. However, simultaneous intra- and extrahepatic recurrence may not see any survival benefit from surgical management. Conclusion Surgical resection of recurrent ICC could improve survival after recurrence, especially for patients with intra- or extrahepatic recurrence as resectable oligo-metastases

Beneficial Effects of Estrogen in a Mouse Model of Cerebrovascular Insufficiency

BACKGROUND: The M(5) muscarinic acetylcholine receptor is known to play a crucial role in mediating acetylcholine dependent dilation of cerebral blood vessels. Previously, we reported that male M(5) muscarinic acetylcholine knockout mice (M5R(-/-) mice) suffer from a constitutive constriction of cerebral arteries, reduced cerebral blood flow, dendritic atrophy, and short-term memory loss, without necrosis and/or inflammation in the brain. METHODOLOGY/PRINCIPAL FINDINGS: We employed the Magnetic Resonance Angiography to study the area of the basilar artery in male and female M5R(-/-) mice. Here we show that female M5R(-/-) mice did not show the reduction in vascular area observed in male M5R(-/-) mice. However, ovariectomized female M5R(-/-) mice displayed phenotypic changes similar to male M5R(-/-) mice, strongly suggesting that estrogen plays a key role in the observed gender differences. We found that 17beta-estradiol (E2) induced nitric oxide release and ERK activation in a conditional immortalized mouse brain cerebrovascular endothelial cell line. Agonists of ERalpha, ERbeta, and GPR30 promoted ERK activation in this cell line. Moreover, in vivo magnetic resonance imaging studies showed that the cross section of the basilar artery was restored to normal in male M5R(-/-) mice treated with E2. Treatment with E2 also improved the performance of male M5R(-/-) mice in a cognitive test and reduced the atrophy of neural dendrites in the cerebral cortex and hippocampus. M5R(-/-) mice also showed astrocyte swelling in cortex and hippocampus using the three-dimensional reconstruction of electron microscope images. This phenotype was reversed by E2 treatment, similar to the observed deficits in dendrite morphology and the number of synapses. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that M5R(-/-) mice represent an excellent novel model system to study the beneficial effects of estrogen on cerebrovascular function and cognition. E2 may offer new therapeutic perspectives for the treatment of cerebrovascular insufficiency related memory dysfunction

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Compartive Studies of Catalase, Cytochrome Oxidase, and Succinic Dehyrogenase of some Animal Tissues

The blood catalase level of ducks is known to be quite low, but no increased activity of cytochrome systems was observed in several tissues of ducks compared with the other animals

The Effect of Sugar Metabolites upon Ketosis of Alloxan Diabetic Rabbit

The administration of oxaloacetate, citrate, succinate, and fructose caused a decrease in ketonuria in alloxan diabetic rabbits, while glucose and fat increased ketone body urinary excretion in rabbits fed alloxan. However, all these substances administered caused a increase in urinary sugar excretion in rabbits fed alloxan