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Biomedical subjects

O Kimura

Publications and source records attributed to O Kimura.

At least 19 recordsLinked to original sources

A clinical analysis of prognostic parameters of survival in children with congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) still has a high mortality because of accompanying lung hypoplasia and persistent pulmonary hypertension. Although prognostic parameters based on perinatal measurements have been proposed, our ability to accurately predict the surgical results remains insufficient. METHODS: We treated 55 infants with CDH from 1981 to 2004. Among them, 46 patients presented respiratory distress within the first 24 hours of life. Results of surgical treatment in the 46 infants were retrospectively correlated with gender, birth weight, gestational age at diagnosis, laterality, cardiac anomalies, diaphragmatic defect area, contents of herniated viscera, and the great vessel diameters measured by echocardiography. RESULTS: Out of 46 CDH neonates, 27 (58.7 %) survived and 19 (41.3 %) died aged 3 to 17 days. Non survivors had a significantly larger diaphragmatic defect and more frequent liver herniation. Out of possible predictive parameters studied, an index of the main pulmonary artery (cross-sectional area/diaphragmatic defect area ratio) most closely correlated with the surgical outcomes. CONCLUSIONS: The postoperative prognosis of CDH infants does not depend only on pulmonary hypoplasia, but also on other factors including the magnitude of abdominal visceral herniation. In this series of patients, the most reliable prognostic predictor was a clinical index reflecting the degree of both pulmonary hypoplasia and diaphragmatic maldevelopment.

Female↗

Estimation of physiologic ability and surgical stress (E-PASS) for a surgical audit in elective digestive surgery.

BACKGROUND: This study was undertaken to establish an equation to estimate mortality with the use of the prediction scoring system designated as the Estimation of Physiologic Ability and Surgical Stress (E-PASS), and to evaluate the system's usefulness in defining quality of care by comparing it with the Physiologic and Operative Severity Score for the enUmeration for Mortality and morbidity (POSSUM) and Portsmouth-possum (P-POSSUM) scoring systems previously generated for surgical audit. METHODS: Patients (n=5212; group A) who underwent elective gastrointestinal surgery were analyzed to establish equations for estimated 30-day and in-hospital mortality rates. The usefulness of E-PASS was evaluated in another series of 1934 patients (group B) who underwent elective digestive surgery in 6 national hospitals. The ratio of observed to estimated mortality rates (OE ratio) of each hospital was defined as a measure of quality. RESULTS: In group A, 30-day and in-hospital mortality rates increased as the Comprehensive Risk Score (CRS) increased, providing equations for estimated mortality rates. There was an excellent correlation between the estimated and observed mortality rates in individual diseases: R=0.958, N=6, P=.0027 for in-hospital mortality; R=0.937, N=6, P=.0059 for 30-day mortality. In all patients of group B, the E-PASS system estimated the 30-day mortality rates by 0.63-fold (linear analysis), whereas the POSSUM score was 11.0-fold (exponential analysis). The E-PASS system estimated the in-hospital mortality rates by 1.2-fold (linear analysis), whereas the P-POSSUM score was 4.5-fold (linear analysis). The OE ratios for 30-day mortality among the 6 hospitals defined by E-PASS correlated well with those defined by POSSUM: R=0.996, N=6, P<.0001. Similarly, the OE ratios for in-hospital mortality defined by E-PASS were also highly correlated with those defined by P-POSSUM:(R=0.929, N=6, P=.0075. CONCLUSIONS: The E-PASS scoring system may be useful in defining surgical quality and may be more accurate than existing systems in evaluating elective digestive surgery.

Digestive System Surgical Procedures↗

The treatment of rectal prolapse in children with phenol in almond oil injection.

PURPOSE: The treatment of rectal prolapse in children is controversial. We report the results of injection sclerotherapy in children using phenol in almond oil (PAO) and discuss the occurrence of complications after the injection of PAO. METHODS: Nine children with rectal prolapse, aged from 2 years and 6 months to 14 years, were treated by PAO injection sclerotherapy between 1993 and 2000. The outcome of PAO injection sclerotherapy and the presence of complications were investigated from the point of anorectal function using anorectal manometry. RESULTS: All of the nine patients were cured after one to three injections without any complications. The manometric study showed that normal anorectal reflex and other parameters of the anorectum were found after injection sclerotherapy. Two of the 4 who had complained of constipation no longer had constipation after the therapy. CONCLUSIONS: PAO injection sclerotherapy is simple and should be recommended as a first method of treatment for rectal prolapse in children. PAO as a sclerosing agent did not cause any complications.

Adolescent↗

Histological investigations into the difference between cystic and fusiform types of congenital biliary dilatation.

We investigated the histological differences in the common bile duct wall of bile ducts with congenital biliary dilatation, examining 10 cystic types and 11 fusiform types. A flattened mucosa was found in the cystic type, and a tufted mucosa was occasionally found in the fusiform type. Glands in the choledochus wall were less common in the cystic type than in the fusiform type. Smooth muscle fibre was more abundant in the cystic type than in the fusiform type, and it was markedly developed in the distal choledochus in the cystic type. Based on these results we suggest that the developmental difference of smooth muscle fibres in the distal choledochus in the embryonic period may be closely related to the morphological difference between the cystic and fusiform types of congenital biliary dilatation.

Bile Ducts↗

Evaluation of an Estimation of Physiologic Ability and Surgical Stress (E-PASS) scoring system to predict postoperative risk: a multicenter prospective study.

We previously reported generating a scoring system termed E-PASS that predicted postsurgical risk. This study was undertaken to evaluate the usefulness of this system. A consecutive series of 902 patients who underwent elective gastrointestinal operations in six national hospitals in Japan were prospectively assessed for a comprehensive risk score (CRS) of the E-PASS, which was compared with their postoperative course. The postoperative morbidity rates linearly increased as the CRS increased. The postoperative mortality rate was only 0.13%, when the CRS was below 0.5; however, it increased to 9.7% when the CRS ranged from 0.5 to <1.0, and to 26.9% when the CRS was > or =1.0. The CRS correlated significantly with the severity of postoperative complications (rs = 0.527, P < 0.0001) and the costs of hospital stay (rs = 0.810, P < 0.0001). When the CRS-adjusted mortality rate at the CRS of > or =0.5 was compared among the hospitals, it was related to the hospital volume of operations, being 44.2% at the volume of <100 cases per year, 20.6% at the range of 100-199 cases, and 8.6% at the volume of > or =200 cases. These results suggest that E-PASS may be useful for predicting postsurgical risk, estimating medical expense, and comparing surgical quality.

Adolescent↗

Impaired distribution of retinoic acid receptors in the hindgut-tailgut region of murine embryos with anorectal malformations.

BACKGROUND/PURPOSE: Retinoid-mediated signal transduction plays a crucial role in the organogenesis of various organs. To investigate the pathogenesis of anorectal malformations (ARM), the authors studied the distribution pattern of retinoic acid receptors (RARs) in ARM murine embryos induced by overdose of all-trans retinoic acid (ATRA). METHODS: Pregnant mice were gavage-fed 100 mg/kg of ATRA on the ninth gestational day (E9.0). Embryos were obtained between E11.0 and E14.0 and were fixed immediately in a 4% paraformaldehyde solution. Frozen sections were prepared for immunohistochemistry using antibodies specifically raised against RAR-alpha, RAR-beta, and RAR-gamma. RESULTS: Over 98% of the embryos administered ATRA had ARM; rectoprostatic urethral and rectocloacal fistulas were the most frequent anomalies. The immunoreactivity of RAR-alpha was found equally in the epithelium of hindgut-tailgut in normal embryos on E11.5. However, it was absent in the hindgut in the treated embryos. The immunoreactivities of RAR-beta and RAR-gamma showed no difference in the distal hindgut. CONCLUSIONS: Impaired distribution of RAR-alpha in the hindgut-tailgut on E11.5 resulted in the incomplete partitioning of the cloaca and the rectourethral or rectocloacal fistula on E14.0. These results suggest that overdose of ATRA affects the distal hindgut development by directly disrupting the retinoid-mediated signalling pathway.

Anal Canal↗

Relationship between the type of RET/GDNF/NTN or SOX10 gene mutations and long-term results after surgery for total colonic aganglionosis with small bowel involvement.

BACKGROUND/PURPOSE: Germline mutations of the RET-mediated or SOX10-mediated signaling pathway genes have been reported in total colonic aganglionosis (TCA). The authors investigated the possible relationship between the type of such genomic abnormalities and surgical outcomes. METHODS: Sixteen patients with TCA with extensive small bowel involvement were studied. DNA sequences of all the RET/GDNF/NTN and SOX10 coding regions were determined by the direct DyeDeoxy Terminator Cycle method. Data on the patients' clinical courses were obtained retrospectively from their medical charts and surgical records. RESULTS: RET or SOX10 germline mutations were identified in 11 of the 16 patients (68.8%). In children with aganglionosis up to the jejunum or ileum, most grew up within normal ranges, and the frequency of bowel movements decreased to 2 to 4 times per day within 5 years. However, in 5 infants with total intestinal aganglionosis, only 2 survived beyond 2 years of age, both of whom underwent Ziegler's myectomy-myotomy. A SOX10 mutation was identified in an infant with Shah-Waardenburg's syndrome, and he showed persistent bowel malfunction. CONCLUSION: The existence or type of RET mutation usually did not affect surgical results in this series of TCA patients, whereas the mutational analysis suggested 2 disease categories of TCA showing different postoperative courses, which may reflect the disparate pathogenesis in the enteric nervous system development induced by impaired RET or SOX10 signaling pathway.

Body Height↗

Factors of biliary carcinogenesis in choledochal cysts.

The long-term complications of choledochal cysts include malignant degeneration of the epithelial lining of the biliary tract. Possible factors leading to malignant degeneration were examined by measuring amylase levels in the biliary tract, intraoperative biliary manometry and a histopathological study. 27 patients, 1 to 13 years of age, with choledochal cysts, were studied over a 13-year period. Amylase levels in the bile of choledochal cysts and the gallbladder were measured. The pressure profile of the biliary tract was recorded as the probe was withdrawn from the sphincter of Oddi (SO) to the distal end of the common bile duct. Hyperplasia of the gallbladder mucosa and malignancy of the biliary tract were investigated. Patients with high levels of biliary amylase had higher pressure differences between the SO and the duodenum than those with low levels of biliary amylase. The incidence of mucosal hyperplasia of the gallbladder mucosa was significantly higher in the fusiform type than in the cystic type. Adenocarcinoma in a cystic choledochal dilatation was found in a 12-year-old girl with high amylase levels. The cause of regurgitation of pancreatic juice into the biliary system might be due to a high pressure difference between the SO and the duodenum in addition to the lack of sphincter function at the abnormal junction of the pancreaticobiliary ductal system. Early diagnosis and surgical treatment to prevent the regurgitation leading to hyperplasia and malignancy of the biliary tract are important for children with choledochal cysts.

Adolescent↗

Secretory transport of cadmium through intestinal brush border membrane via H(+)-antiport.

The effect of pH on the secretory transport of Cd through the intestinal brush border membrane was investigated using isolated rat intestinal brush border membrane vesicles (BBMV) and the Caco-2 intestinal epithelial cell line. BBMV equilibrated at pH 5.5 or 7.5 (pH(in)) were mixed with an experimental buffer at pH 5.5 or 7.5 (pH(out)) containing CdCl(2). The initial accumulation of Cd in BBMV incubated for 1 or 3 min at pH(in) 5.5 and pH(out) 7.5 (outwardly directed H(+)-gradient) was significantly higher than that at pH(in)=pH(out)=7.5, but the equilibrated Cd accumulation incubated for 30 min was marginally lower. Carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), a protonophore, diminished the increasing effect of the H(+)-gradient on the initial Cd accumulation. Caco-2 cell monolayers cultured on permeable membranes were incubated with CdCl(2) from the basolateral medium, and the transport of Cd from the basolateral to apical medium and the accumulation of Cd in the monolayers were measured. Cd transport was increased by lowering the pH of the apical medium, and was accompanied by a decrease in the Cd accumulation. Coincubation with CdCl(2) and tetraethylammonium, a typical substrate for H(+)-antiport of the renal organic cation transporter, from the basolateral medium slightly but significantly decreased the basolateral-to-apical transport of Cd, with a concomitant increase in the Cd accumulation. These findings suggest the secretory transport of Cd through the intestinal brush border membrane not only via passive diffusion but also via H(+)-antiport of the putative organic cation transporter.

Biological Transport↗

Carrier-mediated uptake of cisplatin by the OK renal epithelial cell line.

The purpose of this study was to investigate whether transport of cis-diamminedichloroplatinum II (cisplatin) across renal epithelial cell line OK cells is mediated by the organic cation transport system. OK cell monolayers cultured on permeable membranes were incubated with 100 microM cisplatin on the apical or basolateral side, and the cellular accumulation and the transport of cisplatin across the monolayer were measured. The accumulation from the basolateral medium and the basolateral-to-apical transport of cisplatin were higher than the accumulation from the apical medium and the apical-to-basolateral transport, respectively. The cell monolayers were incubated with different concentrations of cisplatin (0.02 approximately 3 mM) in the basolateral medium. The relationship between the cisplatin concentrations in the medium and in the cells revealed that cisplatin accumulation tended to be saturable. The basolateral-to-apical transport of cisplatin was increased when the pH of the apical medium was decreased, with a concomitant decrease in the accumulation of cisplatin. Coincubation of cisplatin with tetraethylammonium (TEA), a typical substrate for the organic cation transporter, significantly decreased the accumulation and transport of cisplatin from the basolateral medium. These results suggest that the uptake and basolateral-to-apical transport of cisplatin are mediated by not only simple diffusion but also by the organic cation transport system.

Algorithms↗

[Effect of radiotherapy for inoperable remnant and recurrent gastric cancer--focusing of improvement in quality of life].

We investigated six cases of inoperable remnant and recurrent gastric cancer treated with radiotherapy with regard to quality of life (QOL). The radiation dose was from 22 to 70 Gy, with a mean dose of 46 +/- 18 Gy. Four cases could be evaluated. Two were PR and two were NC. No patients could ingest food before radiotherapy, but two became able to eat whole gruel, one half gruel and three water. The mean survival time was 5.5 months and prognosis was not improved. Subjective symptoms such as food passage disturbance were decreased by radiotherapy and QOL was improved. Radiotherapy for patients with inoperable gastric cancer seemed to be effective in improving QOL.

Aged↗

Further analysis of cadmium uptake from apical membrane of LLC-PK1 cells via inorganic anion exchanger.

This study was undertaken to analyze Cd uptake via the inorganic anion exchanger (HCO3-/Cl-) by LLC-PK1 cells cultured on permeable membranes. LLC-PK1 cells were incubated at 37 degrees with 1 microM CdCl2 added to the apical medium, and Cd accumulation in the cells was fractionated into a membrane-bound (non-internalized) Cd fraction and an internalized Cd fraction using ethyleneglycol-bis-(beta-aminoethylether)-N,N,N',N'-tetraace tic acid (EGTA), a chelating agent for Cd. Incubation at a lower temperature (4 degrees) significantly decreased the membrane-bound Cd fraction, and drastically decreased the internalized Cd fraction. Addition of NaHCO3 (a stimulator of Cd uptake via inorganic anion exchanger) to the apical medium significantly increased both membrane-bound and internalized Cd fractions, and this increase was greater for the internalized fraction. Pretreatment of cells with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), a specific inhibitor of inorganic anion exchangers, significantly decreased the internalized Cd fraction without changing the membrane-bound Cd fraction. Addition of NaHCO3 did not effect both Cd fractions in DIDS-pretreated cells. These results suggest that most of Cd binds non-specifically to the apical membrane surface and then is internalized via simple diffusion and some Cd specifically binds to the inorganic anion exchanger and is internalized in a metabolism-dependent manner.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Bidirectional transport of cadmium across apical membrane of renal epithelial cell lines via H+-antiporter and inorganic anion exchanger.

The purpose of this study was to investigate whether cadmium (Cd) efflux across the apical membrane of renal epithelial cells is mediated via a H+-antiport system, and to confirm the re-uptake of Cd from the apical membrane via an inorganic anion exchanger. LLC-PK1 and OK cell monolayers cultured on permeable membranes were incubated with 1 microM CdCl2 added to the basolateral medium, and the transport of Cd from the basolateral to apical medium and the accumulation of Cd in the monolayers were measured. Cd transport was increased by lowering the pH of the apical medium and was accompanied by a decrease in Cd accumulation. Coincubation with N'-methylnicotinamide or cisplatin, which act as substrates of the H+-antiport systems, decreased Cd transport and increased Cd accumulation in a concentration-dependent manner. To confirm the re-uptake of Cd, LLC-PK1 cell monolayers were pretreated with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), a specific inhibitor of an inorganic anion exchanger, before incubation with CdCl2. Pretreatment with DIDS significantly increased Cd transport and decreased Cd accumulation at an apical medium pH of 7.4, but not at pH 5.5. These results suggest bidirectional transport of Cd across the apical membrane of renal epithelial cells via a H+-antiport system (efflux) and an inorganic anion exchanger (influx), depending on the pH of the apical side.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

pH-dependent transport of cadmium in rat renal brush border membrane vesicles: cadmium efflux via H+-antiport.

The effects of pH on the Cd efflux across the renal brush border membrane were investigated using isolated rat renal brush border membrane vesicles (BBMV). BBMV equilibrated at pH 5.5 or 7.5 (pHin) were mixed with an experimental buffer at pH 5.5 or 7.5 (pHout) containing CdCl2. After the incubation with CdCl2, BBMV were washed with a chelating agent, EGTA, to remove Cd bound to the outer surface of BBMV. The initial accumulation of Cd in BBMV incubated for 1, 3 or 5 min at pHin = 5.5 and pHout = 7.5 (outwardly directed H+-gradient) was significantly higher than that at pHin = pHout = 7.5, but the equilibrated Cd accumulation incubated for over 15 min was almost the same. FCCP, a protonophore, diminished the increasing effect of the H+-gradient on the initial Cd accumulation, whereas valinomycine, a K+ ionophore, did not. Kinetic analysis of the Cd accumulation incubated with different concentrations of CdCl2 suggests that Cd is taken up into BBMV via the unsaturable component and saturable component and the outwardly directed H+-gradient increases the Vmax value of the saturable component. The BBMV were incubated with CdCl2 at different temperatures under the outwardly directed H+-gradient, and the increase in Cd accumulation due to the gradient was analyzed by an Arrhenius plot. The plot of increased Cd accumulation was nonlinear, suggesting the involvement of a carrier-mediated process. These findings suggest that the outwardly directed H+-gradient increases the Cd efflux across the renal brush border membrane via H+-antiport system.

Animals↗

Cadmium uptake from apical membrane of LLC-PK1 cells via inorganic anion exchanger.

Effects of Na+, Cl-, OH- and HCO3-, and an inorganic anion exchange inhibitor (HCO3-/Cl-), 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, on Cd uptake from the apical membrane of LLC-PK1 cells were investigated to elucidate the mechanism of Cd uptake by these cells. Furthermore, the initial uptake of Cd incubated at different temperatures was analyzed by using the Arrhenius plot to test if Cd is taken up by the cells via the carrier-mediated process. The cells were incubated with 1 microM CdCl2 for 30 min. at 37 degrees in phosphate buffer containing NaCl at pH 5.5 or 7.4. Cd accumulation by the cells at pH 7.4 was about 5 times higher than at pH 5.5. Replacement of NaCl in the phosphate buffer with KCl or mannitol decreased the Cd accumulation at pH 7.4 about 80%, but had no effect at pH 5.5. The addition of 2 mM NaHCO3 to the pH 7.4 buffer containing NaCl significantly increased the Cd accumulation, and pretreatment of the cells with the inorganic anion exchange inhibitor abolished this effect of NaHCO3 on Cd accumulation. The cells were incubated for 10 min. at different temperatures with 1 microM CdCl2 in the phosphate buffer containing NaCl at pH 7.4 in the presence or absence of 2 mM NaHCO3 or at pH 5.5 in the absence of NaHCO3. In all cases, the Arrhenius plots of Cd accumulation were nonlinear. The breakpoint was observed at about 30 degrees in the Cd accumulation at pH 7.4 in the presence of NaHCO3, suggesting the involvement of a carrier-mediated process. This breakpoint was not as clear in the Cd accumulation at pH 7.4 in the absence of NaHCO3 and not observed at all at pH 5.5. These findings suggested that Cd is partially taken up from the apical membrane of LLC-PK1 cells via the inorganic anion exchanger and the uptake of Cd is more efficient at alkaline pH and in the presence of Na+, Cl- and HCO3-.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗