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Biomedical subjects

Hiroyuki Kobayashi

Publications and source records attributed to Hiroyuki Kobayashi.

At least 145 records · Page 8Linked to original sources

Laparoscopically assisted anorectovaginoplasty for selected types of female anorectal malformations.

PURPOSE: The aim of this study was to describe laparoscopically assisted anorectovaginoplasty (LAARVP) for the repair of selected types of female anorectal malformation. METHODS: Five cases (case 1, rectovaginal fistula with a high rectum; case 2, rectovestibular fistula with double vagina; case 3, rectovestibular fistula with absent vagina; case 4, anovestibular fistula with absent vagina; case 5, cloaca) were reviewed. RESULTS: Patient 4 had undergone a posterior sagittal anorectoplasty without vaginoplasty at another hospital after misdiagnosis of simple anovestibular fistula. Mean age at LAARVP was 15.4 months. At LAARVP, the fistula was divided in cases 1 through 4 and dissected as low as possible in case 5. In cases 3 and 4, the distal fistula was used to create the neovagina. In cases 1 through 3, the proximal rectum was mobilized and brought through the pelvic floor sphincter muscles using Georgeson's laparoscopically assisted colon pull-through technique through a minimal perineal incision. A posterior sagittal incision was required in cases 4 and 5. However, the initial laparoscopic approach was very helpful in both cases. Currently, all patients are well after a mean follow-up period of 32.2 months. Mean current age is 4.0 years. Patients 1 through 3 are continent, patient 4 is incontinent with soiling, and patient 5 is too young to be evaluated. CONCLUSIONS: LAARVP helps to achieve low dissection of the fistula, gives optimal view of the pelvic organs, provides accurate placement of the anorectal pull-through, and minimizes abdominal perineal scars.

Anal Canal↗

The intussusception antireflux valve is ineffective for preventing cholangitis in biliary atresia: a prospective study.

PURPOSE: Cholangitis after Kasai portoenterostomy for biliary atresia (BA) strongly influences outcome, and an intussusception antireflux valve (IAV) in the Roux-en-Y limb has been advocated for the prevention of cholangitis without definitive evidence. The authors report a prospective study to evaluate the effectiveness of IAV in BA. METHODS: Twenty-one consecutive patients with uncorrectable-type BA were the subjects for this study. IAV was included based on informed parental request to give 2 groups: IAV- (n = 11) and IAV+ (n = 10). The incidence/duration of episodes of cholangitis (temperature > 38 degrees C, elevated serum bilirubin level, and leukocytosis) during the first 6 months after Kasai were statistically compared between the 2 groups (P >.05 was regarded as not significant). RESULTS: Technical variations in surgical technique were minimized because the same surgeon supervised all procedures. There were no significant differences between the 2 groups for age and weight at the time of Kasai, mean size of bile ductules at the porta hepatis, and degree of liver cirrhosis present. Protocols for antibiotic and steroid therapy were the same for both groups. The total number of patients who had cholangitis in the IAV- group was 6 of 11 and 5 of 10 in the IAV+ group (P = NS). The total number of episodes of cholangitis was 16 in the IAV- group versus 17 in the IAV+ group (P value, not significant). The mean duration of an episode of cholangitis (number of days per number of episodes) was 12 +/- 6 days in the IAV- group versus 11 +/- 7 days in the IAV+ group (P value, not significant). CONCLUSIONS: IAV does not make any significant impact on the incidence or duration of cholangitis in the early post-Kasai period.

Anastomosis, Roux-en-Y↗

Forme fruste choledochal cyst: long-term follow-up with special reference to surgical technique.

PURPOSE: Forme fruste choledochal cyst (FFCC) is a choledochal cyst that has minimal or no dilatation of the extrahepatic bile duct (EHBD) and is associated with pancreaticobiliary malunion (PBMU). The authors reviewed the long-term outcome of their patients with FFCC. METHODS: Inpatient and outpatient records of 281 patients with choledochal cyst were reviewed. In this study, minimal dilatation of the EHBD was defined as its maximum diameter being less than 10 mm. RESULTS: There were 17 cases of FFCC identified. In all 17 patients, PBMU was present. The mean age at EHBD excision was 2.9 years. Fourteen patients had hepatico-jejunostomy, and three had hepatico-duodenostomy. The histology of the excised EHBD showed mucosal ulceration/sloughing (in 35.3% patients), fibrosis (52.9%), and inflammatory cell infiltration (41.2%). Over a mean postoperative follow-up period of 9.8 years, there have been no episodes of cholangitis or anastomotic stricture formation. CONCLUSIONS: The treatment of choice for FFCC in children is EHBD excision and hepatico-jejunostomy. There is little surgical morbidity if performed carefully.

Bile Ducts, Extrahepatic↗

Recommendations for preventing complications related to Roux-en-Y hepatico-jejunostomy performed during excision of choledochal cyst in children.

PURPOSE: The aim of this study was to review the outcome of a protocol the authors proposed for preventing Roux-en-Y hepatico-jejunostomy (RYHJ) related complications. METHODS: In 1986 the authors adopted the following protocol for improving RYHJ to minimize risks for RY-related complications: (1) end-to-end anastomosis if possible; (2) if end-to-side anastomosis is unavoidable, the common hepatic duct should be anastomosed as close as possible to the closed end of the blind pouch (BP); (3) careful selection of the vascular supply to the RY jejunal limb; (4) length of the RY jejunal limb should not be predetermined, but individualized; (5) approximate the native jejunum to the RY limb. The authors reviewed 92 children who had surgery for CC (mean age at surgery, 4.1 years) at our institution between 1986 and 2002 to assess the effectiveness of their recommendations. RESULTS: After the adoption of the authors' recommendations for RYHJ, they have experienced no RYHJ-related complications after a mean follow-up period of 7.6 years (range, 4 months to 16 years). CONCLUSIONS: RYHJ in children is different from that in adults, because the RY limb or BP can grow and elongate as the child grows. The authors' recommendations appear to have successfully prevented RY-related complications up to the time of this review, and they highly recommend their use.

Adolescent↗

A novel technique for reinforcing the neourethra in hypospadias associated with bilateral undescended testis: use of the gubernaculum.

The authors present 3 cases of proximal hypospadias associated with bilateral undescended testes (UDT) in which the gubernaculum was used to reinforce the neourethra to prevent urethrocutaneous fistula. This is the first report of the gubernaculum being used to reinforce the neourethra. The technique is simple and should be applicable to any hypospadias patient with concomitant UDT, especially in severe hypospadias. Good outcome is likely because of the excellent blood supply of the gubernaculum.

Child, Preschool↗

Role of immunologic costimulatory factors in the pathogenesis of biliary atresia.

BACKGROUND: The authors studied the patterns of expression of immunologic costimulatory molecules (B7-1, B7-2, and CD40) in biliary atresia (BA) patients to confirm any correlation with clinical course/outcome. METHODS: Based on clinical status 2 years postoperatively, 24 BA patients were divided into group I (n = 8, normal liver function), group II (n = 10, anicteric with moderate liver dysfunction), and group III (n = 6, icteric with severe liver dysfunction). Liver biopsies obtained at portoenterostomy and from 6 age-matched controls, were analyzed immunohistochemically using antibodies against B7-1, B7-2, and CD40. RESULTS: There was no expression of B7-1, B7-2, or CD40 in any control liver specimen. In all BA specimens, B7-1, B7-2, and CD40 were expressed strongly in bile ductules in portal tracts. In groups with liver dysfunction, B7-1, B7-2, and CD40 were expressed strongly on the surfaces of Kupffer and dendritic cells and in hepatocyte cytoplasm. Positive staining cells were significantly fewer in patients with better clinical outcome. B7-1 was found in vascular and sinusoidal endothelial cells only in cases of postoperative portal hypertension. CONCLUSIONS: Costimulatory factors expressed on bile ductules, hepatocytes, and vascular endothelial cells appear to mediate autoimmune processes causing progressive liver fibrosis and portal hypertension in BA.

Antigens, CD↗

Living-related partial bladder transplantation for bladder augmentation in rats: an experimental study.

PURPOSE: To assess the feasibility of transplanting adult bladder tissue to its offspring as a source of neobladder tissue for bladder augmentation. METHODS: The dome of the bladder of an adult Lewis rat was excised and transplanted into the omentum of a 6-week-old offspring (living-related partial bladder transplant: n = 15). The bladder remnant of the donor rat was closed. Two weeks after transplantation, a laparotomy was performed to mobilize the bladder graft with its omental pedicle into the pelvis. Bladder augmentation (BA) was performed by anastomosing the graft to the recipient's bladder. Thirty days after BA, the entire neobladder was excised and histopathologically examined. RESULTS: At laparotomy, each bladder graft appeared macroscopically as a thin-walled cyst in the recipient's omentum. Each graft could be mobilized into the pelvis and anastomosed to the recipient's bladder. BA was successful in all 15 recipients, and histopathologic studies showed that the mucosa was normal throughout each neobladder. Postoperatively, donors and recipients were clinically well without any sign of urinary incontinence or obstruction. CONCLUSIONS: This is the first report of adult tissue being transplanted successfully into a recipient without vascular reconstruction in a rat. Living-related partial bladder transplantation for the purpose of BA is feasible using our technique and could have application as an alternative technique for BA in a rat.

Anastomosis, Surgical↗

Soluble IL-4 receptor improves the skin-graft-associated cytomegalovirus infection in thermally injured mice.

The susceptibility of thermally injured mice (TI-mice) to murine cytomegalovirus (MCMV) infection is markedly influenced by burn-associated type 2 T cell responses, which are common with severe thermal injuries. In the present study, the effect of soluble IL-4 receptor (sIL-4R) on the skin-graft-associated MCMV infection was investigated. The marked growth of MCMV was demonstrated in the salivary glands of TI-mice grafted with MCMV seropositive [MCMV sero(+)] skin. However, the growth of MCMV was not demonstrated in the salivary glands of TI-mice grafted with MCMV sero(+) skin and treated with 50ng per mouse of sIL-4R. Compared with grafted normal mice, production of type 1 cytokines was markedly decreased when splenic T cells from TI-mice grafted with MCMV sero(+) skin were stimulated with anti-CD3 monoclonal antibody (mAb). The impaired type 1 cytokine production was recovered in cultures of splenic T cells from grafted TI-mice previously treated with sIL-4R. After grafting with MCMV sero(+) skin, the growth of MCMV was markedly inhibited in the salivary glands of severe combined immunodeficient (SCID) mice inoculated with T cells from TI-mice treated with sIL-4R. These results suggest that sIL-4R regulates the skin-graft-associated MCMV infection in TI-mice.

Analysis of Variance↗

Primary mucinous cystadenoma arising from behind the posterior peritoneum of the descending colon in a child: a case report.

This is the first report of a primary mucinous cystadenoma (MCA) arising from behind the posterior peritoneum of the descending colon in a paediatric patient. A large intra-abdominal cystic lesion was found incidentally during renal ultrasonography in a 14-year-old girl. Imaging studies showed a 13 x 9 x 15 cm homogeneous cystic lesion with mild contrast enhancement of the wall. The cyst appeared to originate from the retroperitoneum, but was separated from the left kidney, ovary, and pancreas. At laparotomy, there was a cyst behind the posterior peritoneum of the descending colon. The cyst was successfully excised, and histopathology showed MCA. Although primary MCA in the retroperitoneum is extremely rare in children, it should be considered in the differential diagnosis of an intra-abdominal cyst, since it needs to be excised to eliminate the risk of infection, recurrence, and malignancy.

Adolescent↗

Biliary atresia.

Biliary atresia (BA) is a congenital obliterative cholangiopathy of unknown aetiology, affecting both the intra- and extrahepatic bile ducts. Although relatively rare, BA must be excluded in any infant with conjugated hyperbilirubinaemia since the prognosis is improved by early diagnosis and prompt surgery. At least two phenotypes of BA are currently recognized; the syndromic variety is associated with other congenital anomalies and a poorer outcome. The results of treatment have steadily improved and, with a combination of timely expert surgery (Kasai portoenterostomy) and liver transplantation in specialist centres, good quality long-term survival is now possible in more than 90% of affected patients. A better understanding of the aetiology of BA and the pathogenesis of hepatic fibrosis is needed in order to develop new therapeutic strategies.

Biliary Atresia↗

Different remodelling against left ventricular overload between diabetic and non-diabetic haemodialysis patients.

1. Diabetes mellitus is significantly associated with the occurrence of congestive heart failure in end-stage renal disease patients undergoing maintenance haemodialysis. In the present study, we asked whether the left ventricular remodelling against sustained pressure and/or volume overload to the left ventricle may be different between diabetic and non-diabetic haemodialysis patients. 2. Left ventricular parameters, including left ventricular mass index (LVMI), interventricular septal wall thickness (IVST) and relative left ventricular wall thickness (rLVWT), were assessed in 486 patients receiving maintenance haemodialysis (145 diabetic and 341 non-diabetic patients) using transthoracic echocardiography. Plasma concentrations of B-type natriuretic peptide (BNP), measured with an immunoradiometric assay, were used as a humoral parameter indicating left ventricular wall stress. 3. In non-diabetic patients, the plasma BNP concentration correlated with LVMI (r = 0.245; P = 0.0001), IVST (r = 0.250; P = 0.0001) and rLVWT (r = 0.149; P = 0.006). Furthermore, LVMI was correlated with mean blood pressure and pulse pressure and IVST and rLVWT were correlated with pulse pressure. 4. In contrast, none of the measured factors was correlated with LVMI and IVST in diabetic patients. Plasma BNP concentrations were positively correlated with end-systolic and end-diastolic left intraventricular dimensions and were inversely correlated with rLVWT and left ventricular fractional shortening in diabetic patients, but not in non-diabetic patients. 5. In conclusion, a sustained increase in left ventricular wall stress is likely to elicit eccentric left ventricular remodelling in diabetic haemodialysis patients, whereas it causes concentric left ventricular remodelling in non-diabetic haemodialysis patients. This difference in left ventricular remodelling against left ventricular overload may be associated with the high incidence of congestive heart failure in diabetic haemodialysis patients.

Aged↗

Fibroblast growth factor signaling in the developing tracheoesophageal fistula.

BACKGROUND/PURPOSE: The Adriamycin-induced rat model of esophageal atresia and tracheoesophageal fistula (EA/TEF) provides a reliable system for the study of EA/TEF pathogenesis. The authors previously hypothesized that faulty branching lung morphogenesis pathways were a critical component of its pathogenesis. The authors have found evidence for faulty fibroblast growth factor (FGF) signaling related to epithelial-mesenchymal interactions in the fistula tract. To better define FGF signaling, the differential expression of FGF ligands and their receptors between lung, fistula tract, and esophagus are described. METHODS: Time-dated pregnant, Sprague-Dawley rats were injected with Adriamycin (2 mg/kg intraperitoneally) on days 6 through 9 of gestation. Tissues were processed for histology and reverse transcriptase polymerase chain reaction. FGF-1, -7 and -10 were measured from whole lung, fistula tract, and esophagus of TEF or normal embryos. Expression of FGF2RIIIb and FGF2RIIIc receptors was measured in isolated epithelium and mesenchyme of lung and fistula tract of TEF embryos as well as lung and esophagus from normal controls. RESULTS: FGF-1 mRNA was present in the fistula tract and normal and Adriamycin-exposed lung but absent from whole esophagus. Interestingly, FGF-7 mRNA was present only in normal lung. FGF-10 was present in all tissues examined. FGF2RIIIb mRNA was absent in fistula mesenchyme but present in all other tissues examined. However, the splice variant FGF2RIIIc mRNA was present in all tissues examined. CONCLUSIONS: These findings support defective FGF signaling in the rat model of EA/TEF. Absence of FGF-7 mRNA in Adriamycin-exposed tissues suggests the primary effect of Adriamycin may be to inhibit FGF-7 expression. Moreover, absence of FGF2RIIIb in fistula mesenchyme may be caused by loss of positive feedback from FGF-7, its normal obligate ligand. Understanding these specific defects in FGF signaling may provide insight into faulty mechanisms of EA/TEF.

Abnormalities, Drug-Induced↗

The high incidence of left atrial appendage thrombosis in patients on maintenance haemodialysis.

BACKGROUND: The incidence of intracardiac thrombosis in haemodialysis patients has not been studied. Here we determined the incidence in end-stage renal disease patients on maintenance haemodialysis. METHODS: Transoesophageal echocardiography was performed in 215 patients (125 males, 90 females; mean age 60 +/- 9 years). Any potential candidate with current or past chronic or intermittent atrial fibrillation or with cardiovascular diseases was excluded from the study. RESULTS: Thrombi were found in the left atrial appendages in 71 out of 215 subjects (33%). Based on multiple logistic regression analyses, the probability of finding a thrombus was found to be increased in patients on chronic antiplatelet therapy (odds ratio 4.268) and in those with diabetes mellitus and a low haematocrit (</=0.3; odds ratio 7.173). Other clinical parameters, including gender, age, duration of haemodialysis, blood pressure, left ventricular dimension, smoking habit or type of anticoagulation during dialysis, were not associated with the incidence of left atrial appendage thrombosis. CONCLUSIONS: Maintenance haemodialysis patients have a high incidence of left atrial appendage thrombosis. Either chronic use of antiplatelet drugs or the background conditions requiring antiplatelet therapy, and the concomitant presence of diabetes mellitus and a low haematocrit may be involved in left atrial appendage thrombosis.

Aged↗

Large diversity in transport-mediated methotrexate resistance in human leukemia cell line CCRF-CEM established in a high concentration of leucovorin.

To elucidate the mechanism(s) of methotrexate (MTX) resistance as a possible reason underlying treatment failure in high-dose MTX regimens combined with leucovorin (LV) rescue, we established MTX-resistant human T-cell leukemia cell line CCRF-CEM cells in the presence of excess LV, and characterized their properties. Continuous exposure of the cells to escalating concentrations of MTX up to 20 microM in the presence of 1000 nM LV resulted in establishment of three MTX-resistant sublines with a wide disparity of resistance degree over a 4 logarithmic range (approximately 40-, 900- and 44,000-fold, respectively). Transmembrane transport of MTX in these sublines was diminished to 52%, 35% and 12%, respectively. Intracellular retention of MTX in these sublines was not different from that of the parent cells. A cell growth study in various concentrations of LV showed that cells with higher resistance to MTX required more LV for optimal growth. In parallel with the resistance levels, there was an increase in mRNA expression of dihydrofolate reductase gene and a decrease in that of thymidylate synthase gene, but no change in that of reduced folate carrier (RFC1) gene, as assessed by northern blot analysis. Sequencing of the RFC1 gene in all 3 sublines revealed a point mutation in codon 47 (TCC-->TTC) resulting in substitution of Phe for Ser residue, and additional deletion of CTG of codon 112 in the subline with the highest resistance. In summary, MTX exposure to CCRF-CEM cells in the presence of 1000 nM LV resulted in the establishment of heterogeneous cell populations with a wide range of transport-mediated MTX resistance, which was associated with differential alterations of RFC gene. These cell lines may serve as models for investigation of the molecular mechanism(s) underlying refractory tumors in high-dose MTX regimens with LV rescue.

Amino Acid Substitution↗

Protein synthesis in Escherichia coli with mischarged tRNA.

Two types of aspartyl-tRNA synthetase exist: the discriminating enzyme (D-AspRS) forms only Asp-tRNA(Asp), while the nondiscriminating one (ND-AspRS) also synthesizes Asp-tRNA(Asn), a required intermediate in protein synthesis in many organisms (but not in Escherichia coli). On the basis of the E. coli trpA34 missense mutant transformed with heterologous ND-aspS genes, we developed a system with which to measure the in vivo formation of Asp-tRNA(Asn) and its acceptance by elongation factor EF-Tu. While large amounts of Asp-tRNA(Asn) are detrimental to E. coli, smaller amounts support protein synthesis and allow the formation of up to 38% of the wild-type level of missense-suppressed tryptophan synthetase.

Aspartate-tRNA Ligase↗

Antimicrobials as potential adjunctive agents in the treatment of biofilm infection with Staphylococcus epidermidis.

BACKGROUND: This study was performed to evaluate the interaction of erythromycin or rifampin with vancomycin against Staphylococcus epidermidis biofilms. METHODS: Biofilm-forming S. epidermidis strains (ATCC 35983, 35984) and polyurethane (PU) sheets were incubated for the formation of bacterial biofilms. Biofilms on PU sheets were treated with various antibiotic regimens. The number of viable bacteria on the sheets was counted. RESULTS: While erythromycin or vancomycin alone did not significantly reduce the biofilm bacterial concentration, the combination of vancomycin and erythromycin resulted in a clear reduction in bacterial concentration compared with the single agents. Rifampin was the most active single agent against biofilm-forming S. epidermidis, while the combination of rifampin and vancomycin showed further reduction in bacterial concentration. CONCLUSIONS: These data suggest that the combination of erythromycin or rifampin and vancomycin is more effective than vancomycin alone in the treatment of biofilm infections caused by biofilm-forming S. epidermidis.

Biofilms↗

The contribution of cytochrome P450 to the metabolism of tegafur in human liver.

Fluorouracil (5-FU) prodrug tegafur (FT) is used widely for treating cancer patients. It has been reported that CYP2A6 and thymidine phosphorylase (TP) are involved in the formation of 5-FU from FT. In this study, the relative contribution of cytochrome P450 (P450) to the formation of 5-FU from FT was assessed using human liver 9000 x g supernatant (S9) and hepatocytes, which contain both enzymes. Intrinsic clearances of 5-FU formation from FT by P450 (NADPH dependent) and TP (NADPH independent) in human liver S9 were 1.36 and 0.169 microL/min/mg protein, respectively. The formation of 5-FU from FT in human liver S9 was inhibited over 82% by 8-methoxypsoralen, a CYP2A6-selective inhibitor. The formation of 5-FU from FT was also evaluated in human hepatocytes, cells that not only exhibit P450 and TP activity but also have anabolic capacity. The results indicated that CYP2A6 played a major role in 5-FU formation, which was consistent with the results using human liver S9. Factors that can affect the level of CYP2A6 activity in patients, e.g., genetic polymorphism, should be considered when using FT for chemotherapy.

Journal Article↗