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T Hirota

Publications and source records attributed to T Hirota.

At least 19 recordsLinked to original sources
PubMed2007

Prediction of pharmacokinetics of CS-023 (RO4908463), a novel parenteral carbapenem antibiotic, in humans using animal data.

The pharmacokinetics of CS-023 (RO4908463, formerly R-115685), a novel parenteral carbapenem antibiotic, in humans was successfully predicted using the data collected from mice, rats, rabbits, and dogs; while inclusion of the monkey data led to a significant underestimation of the total plasma clearance (CL). Double logarithmic plots of CL and distribution volume at the steady-state (Vss) vs. body weight in four animal species were linear with high correlation coefficients; and the predicted CL and Vss values in humans agreed well with the observed values after administration of CS-023 by an intravenous drip infusion for 30 min. The plasma concentration-time profile in humans, which was predicted using a bi-exponential equation fitted to a complex Dedrick plot of the animal data, approximated the observed profile. An underestimation of CL caused by including the monkey data in a prediction is quite likely due to the net tubular reabsorption in monkeys, but not at least in rabbits, dogs, and humans.

Animals↗
PubMed2006

Requirement of nectin, but not cadherin, for formation of claudin-based tight junctions in annexin II-knockdown MDCK cells.

Adherens junctions (AJs) and tight junctions (TJs) comprise a junctional complex which plays key roles not only in cell adhesion and polarization but also in regulation of cell movement and proliferation in epithelial cells. E-Cadherin and nectin are major cell-cell adhesion molecules (CAMs) at AJs, whereas claudin is a major CAM at TJs. We have shown that the cadherin-based cell-cell adhesion is not formed in MDCK cells in which annexin II, a Ca(2+)- and phospholipid-binding protein, is knocked down. Here, we found that TJs and the nectin-based cell-cell adhesions were formed in annexin II-knockdown cells. The formation of TJs in annexin II-knockdown MDCK cells required the nectin-based cell-cell adhesion and afadin, a nectin- and actin-filament-binding protein. In addition, it required the activation of Cdc42 and Rac small G proteins and subsequent reorganization of the IQGAP1-dependent actin cytoskeleton which were induced by the nectin-based cell-cell adhesion. These results indicate that the nectin-based cell-cell adhesion and afadin, but not the cadherin-based cell-cell adhesion, are necessary for the formation of TJs and that the signaling by nectin and the subsequent reorganization of the actin cytoskeleton are also necessary for the formation of TJs under certain conditions.

Animals↗
PubMed2006

Renal handling of CS-023 (RO4908463), a novel parenteral carbapenem antibiotic, in rabbits in comparison with meropenem.

The plasma half-life of CS-023 (RO4908463), a novel parenteral carbapenem antibiotic, is longer than that of meropenem in animals and humans. To address this issue, renal clearance studies were conducted in rabbits. A constant rate infusion of CS-023 and meropenem was conducted in male Japanese White rabbits. Concentrations in the plasma, urine and renal cortex were measured to evaluate renal clearance and renal tissue uptake. CS-023 showed a clearance ratio (renal clearance/glomerular filtration rate) of around 1, which was not affected by co-administration of probenecid or p-aminohippurate. On the other hand, meropenem exhibited a clearance ratio of around 3, which was significantly decreased to 1 by co-administration of probenecid. p-Aminohippurate, in contrast, had no effect. The renal cortex/plasma concentration ratio of CS-023 was around 0.6 with or without probenecid co-administration. This ratio of meropenem was around 3, which was decreased significantly by co-administration of probenecid to around 0.6. These data suggest that meropenem is secreted in the renal tubules via organic anion transporters, but CS-023 is not. The present findings in rabbits would indicate that a lack of renal tubular secretion of CS-023 is a reason for the long plasma half-life compared with meropenem.

Animals↗
PubMed2006

A simplified method for continuous hepatic arterial port-catheter system placement not requiring catheter end-hole occlusion.

PURPOSE: To evaluate the efficacy of hepatic port-catheter system placement without distal catheter tip occlusion or gastroduodenal artery embolization distal to the catheter tip. MATERIAL AND METHODS: A port-catheter system was percutaneously implanted in 29 patients (16 men, 13 women; mean age 65.6 years) with unresectable liver cancer. Persistent blood flow through the end hole of the catheter was verified immediately and 1-10 days after catheter placement. RESULTS: In all cases, percutaneous port-catheter placement was successfully performed. In seven of 29 (24.1%) patients, flow through the end hole of the catheter was verified immediately after the procedure. However, no flow was seen 1-10 days after the procedure. CONCLUSION: It is not necessary to occlude the end hole of the catheter tip and embolize the gastroduodenal artery beyond the catheter tip when placing a port-catheter system for repeated hepatic arterial infusion chemotherapy.

Aged↗
PubMed2006

Association between ADAM33 polymorphisms and adult asthma in the Japanese population.

BACKGROUND: ADAM33, a member of the ADAM (a disintegrin and metalloprotease) family, is a putative asthma susceptibility gene recently identified by positional cloning. It is important to know whether the association exists in ethnically diverse populations. OBJECTIVE: To assess whether genetic functional variants of ADAM33 relate to the susceptibility or some phenotypes in adult patients with bronchial asthma in a Japanese population. METHODS: We searched for single nucleotide polymorphisms (SNPs) in ADAM33 by PCR-directed sequencing and identified 48 SNPs. Fourteen SNPs were selected with regard to the LD pattern, and genotyped by Taq-Man and PCR-RFLP methods. We conducted an association study of ADAM33 with 504 adult asthmatic patients and 651 controls, and haplotype analyses of related variants were performed. RESULTS: Significant associations with asthma were found for the SNPs T1 (Met764Thr), T2 (Pro774Ser), S2 and V-3 (with the lowest P-value for T1, P = 0.0015; OR 0.63). We analysed the haplotype using these four polymorphisms, and found a positive association with haplotype CCTG (P = 0.0024). CONCLUSION: Our results replicate associations reported recently in other ethnic populations, and suggest that the ADAM33 gene is involved in the development of asthma through genetic polymorphisms.

ADAM Proteins↗
PubMed2006

Spontaneous regression of gastric varices after iatrogenic injury to a gastrorenal shunt.

We present a patient with gastric varices complicating portal hypertension caused by liver cirrhosis related to hepatitis C virus. The patient underwent balloon-occluded retrograde transvenous obliteration. The gastric varices almost completely disappeared, without any sclerotic agent being used, after iatrogenic injury of the gastrorenal shunt at the time of the interventional procedure.

Balloon Occlusion↗
PubMed2006

Duration of pneumothorax as a complication of CT-guided lung biopsy.

The purpose of this study was to determine management guidelines for biopsy-induced pneumothorax with the assistance of manual aspiration, mainly based on the duration of complicated pneumothorax. Data from 388 consecutive percutaneous needle lung biopsies were examined. Patients with pneumothorax on postbiopsy chest CT images underwent percutaneous manual aspiration with an 18-G i.v. catheter. Frequency and management of biopsy-induced pneumothorax and period to its disappearance were reviewed. Postbiopsy pneumothorax occurred in 133 of 388 (34.3%) procedures. Manual aspiration in 72 of these 133 patients was carried out immediately after biopsy. The pneumothorax had resolved completely on follow-up chest radiographs without chest tube placement in 121 of the 133 pneumothoraces (91.0%). In cases requiring chest tube, the mean period from biopsy until resolution of the pneumothorax was 6.0 +/- 5.3 days, but was only 2.4 +/- 2.9 days when chest tube placement was not needed. Specifically, time until recovery was short both in those not requiring manual aspiration (2.1 +/- 3.4 days) and in those with a pneumothorax that disappeared completely or almost completely after manual aspiration (1.9 +/- 2.0 days). The almost equally short recovery periods in patients not requiring manual aspiration and those requiring immediate manual aspiration indicates the value of rapid management.

Adolescent↗
PubMed2006

Prophylactic implantation of inferior vena cava filter during interventional radiological treatment for deep venous thrombosis of the lower extremity.

The purpose of this study was to evaluate the filtering effect of the Gunther tulip retrievable vena cava filter (GTF) during treatment of deep venous thrombosis (DVT) in the lower extremity using various interventional radiological procedures. Subjects of the study were all 17 consecutive patients (8 women, 9 men; age range 18-87 years; mean age 55.9 years) with symptomatic lower limb DVT referred for interventional radiological treatment between February 2001 and September 2004. In all of these patients, the GTF was implanted during interventional radiological treatment. Trapped thrombus in the filter was evaluated with venocavography performed repeatedly during the treatment for DVT. Implantation of a total of 29 GTFs was successfully performed in the 17 patients. In 10 (58.8%), more than 2 filters were subsequently implanted to prolong implantation time. Also in 10 patients, the DVT resolved after therapy and retrieval of the final GTF was successful with one exception. Worsening of or new formation of pulmonary embolism was avoided in all patients. In 8 (47.1%) of the 17 patients, a trapped thrombus in the GTF was observed during treatment for DVT. In six patients the trapped thrombus was large, filling more than half the height of the filter. In conclusion, we found that the GTF is effective in filtering the relieved thrombus from DVT in the lower extremity and in protecting against movement of the thrombus to the pulmonary artery during therapies with interventional radiological procedures.

Adolescent↗
PubMed2005

A 90-day oral toxicity study of beta-carotene derived from Blakeslea trispora, a natural food colorant, in F344 rats.

A subchronic oral toxicity study of beta-carotene derived from Blakeslea trispora, a natural food colorant, was performed with groups of 10 male and 10 female F344 rats fed the agent at dietary levels of 0%, 0.2%, 1.0% and 5.0% for 90 days. There were no treatment-related adverse effects with regard to body weight, food and water consumption, urinalysis, ophthalmology, hematology, serum biochemistry, and organ weight data. On clinical observation, red coloring of fur was noted in both sexes of the 1.0% and 5.0% group rats, with red feces observed in all treated group animals, and necropsy revealed all rats of the treated groups to have reddish coloration of the contents of the gastro-intestinal tract, due to the pigmentation and thus lacking toxicological significance. On histopathological examination, sporadic spontaneous lesions known to occur in this strain of rats were the only findings, with no specific relation to the test substance. Thus, the no-observed-adverse-effect-level (NOAEL) was judged to be a dietary level of at least 5.0% (3127 mg/kg body weight/day for males, 3362 mg/kg body weight/day for females) for beta-carotene derived from B. trispora under the present experimental conditions.

Animals↗
PubMed2005

The effect of female polyandry and sperm precedence on the evolution of sexual difference in dispersal timing.

Predispersal copulation and unpredictable environment facilitate the evolution of female-biased dispersal in species, where females are functionally monandrous. Females should migrate and reproduce over different habitats to spread their risks due to environmental fluctuation. On the other hand, males do not have to disperse because their risks are spread by their mating partners who produce their offspring in different habitats. However, when females are functionally polyandrous, it is expected that they will not contribute to spreading the male's risk extensively. Therefore, by simulation with the individual based model, the present study evaluated how female polyandry influences the sexual difference in dispersal timing. This model revealed that when females are polyandrous, the timing of female remating and sperm priority patterns have an important influence on the evolution of sex-biased dispersal. Particularly when female remating is not synchronized with dispersal or when last-male sperm precedence does not exist, female-biased dispersal is evolved.

Animal Migration↗
PubMed2005

Gastric ciliated metaplasia. A study of 3406 gastrectomy specimens from dwellers of the Atlantic and the Pacific basins.

BACKGROUND: Ciliated cells in gastrectomies from patients dwelling in the Pacific and Atlantic basins have been reported previously. AIM: To compare all the results in an attempt to explain the findings. METHODS: Sections from 3406 gastrectomies were reviewed: 1966 and 1440 from the Atlantic and Pacific basins, respectively. Ciliated cells and intestinal metaplasia (IM) were recorded; IM was classified into focal or extensive IM. The total number of sections/gastrectomy was noted. RESULTS: In the Atlantic basin, 5% of specimens had ciliated metaplasia (CM); it was more frequent in intestinal carcinoma (IC; 9%) than diffuse carcinoma (DC; 3%) or miscellaneous gastric diseases (MGD; 3%). In the Pacific basin, the frequency of specimens with CM was 29%: it was more frequent in IC (43%) than in DC (16%) or MGD (10%). The difference between the frequency of CM in specimens with IC or with DC/MGD in the Atlantic and the Pacific basins was significant (p < or = 0.05). The presence of CM was influenced by age and the extent of IM in both basins, but not by sex or the number of sections investigated. CONCLUSIONS: CM-apparently an independent microscopic marker-was significantly higher in the Pacific than in the Atlantic basin. Environmental carcinogens involved in the evolution of IM and IC seem to be implicated in gastric ciliogenesis. Carcinogens that differ in nature and/or in strength in both basins might activate the latent natural genes encoding ciliated processes in gastric cells in patients subsequently developing gastric carcinoma, more notably of intestinal type.

Adult↗
PubMed2005

Spontaneous healing of chyle leakage after lymphangiography.

We report a 34-year-old man with the complication of chylous ascites after retroperitoneal lymphadenectomy that was refractory to various conservative therapies. Because surgical treatment for chylous ascites was considered, lymphangiography was performed to identify the area of leakage of chyle, after which the chylous ascites spontaneously healed.

Adult↗
PubMed2004

Association of the hCLCA1 gene with childhood and adult asthma.

Asthma is caused by bronchial inflammation. This inflammation involves mucus overproduction and hypersecretion. Recently, a mouse model of asthma showed that gob-5 is involved in the pathogenesis of asthma. The gob-5 gene is involved in mucus secretion and its expression is upregulated upon antigen attack in sensitized mice. The observation suggests that human homologue of gob-5, hCLCA1 (human calcium-dependent chloride channel-1), may be involved in human disease. We screened for single-nucleotide polymorphisms (SNPs) in hCLCA1 in the Japanese population. We identified eight SNPs, and performed association studies using 384 child patients with asthma, 480 adult patients with asthma, and 672 controls. In haplotype analysis, we found a different haplotype distribution pattern between controls and childhood asthma (P<0.0001) and between controls and adult asthma (P=0.0031). We identified a high-risk haplotype (CATCAAGT haplotype; P=0.0014) and a low-risk haplotype (TGCCAAGT haplotype; P=0.00010) in cases of childhood asthma. In diplotype analysis, patients who had the CATCAAGT haplotype showed a higher risk for childhood asthma than those who did not (P=0.0011). Individuals who had the TGCCAAGT haplotype showed a lower risk for childhood asthma than those who did not (P<0.0001). Our data suggested that variation of the hCLCA1 gene affects patients' susceptibility for asthma.

Adolescent↗
PubMed2004

Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen.

BACKGROUND: A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. OBJECTIVE: The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. CONCLUSION: These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.

ADAM Proteins↗
PubMed2004

Intrahepatic portosystemic venous shunt passing through the left inferior phrenic vein and draining into the left renal vein.

We report a case of an intrahepatic portosystemic venous shunt (IPSVS) passing through the left inferior phrenic vein and draining into the left renal vein and then to the inferior vena cava. We incidentally detected the IPSVS while performing a transcatheter arterial embolisation for the treatment of hepatocellular carcinoma. IPSVS with the left inferior phrenic vein as the draining vein is very rare. The complete pathway of this IPSVS could be clearly demonstrated by multidetector row CT during arterial portography.

Aged↗