Biomedical subjects

Akira Okada

Publications and source records attributed to Akira Okada.

At least 37 records · Page 2Linked to original sources

PubMed2003

FTY720 reduces T-cell recruitment into murine intestinal allograft and prevents activation of graft-infiltrating cells.

BACKGROUND: Effective immunosuppression is a critical determinant of graft survival in small-bowel transplantation (SBTx). The present study was designed to determine the potency of FTY720, a newly synthesized immunosuppressant, in rat SBTx and examine the phenotype of graft-infiltrating cells to evaluate its effect on intestinal allografts. MATERIALS AND METHODS: A segment of intestine of Dark Agouti rats was transplanted heterotopically into Lewis rats. The recipients were treated with or without oral FTY720 at a dose of 1 mg/kg per day. Six days after surgery, peripheral blood lymphocytes and lymphocytes from the mesenteric lymph nodes, Peyer's patches, intraepithelial site, and lamina propria of the intestinal allograft were isolated. After the number of lymphocytes in each site was counted, the lymphocyte subpopulations in the intestinal allograft were evaluated by means of a FACScan flow cytometer using several monoclonal antibodies. RESULTS: FTY720 treatment significantly prolonged recipient survival and strongly inhibited rejection histologically in comparison with control rats. FTY720 immunosuppression resulted in a marked reduction of lymphocyte number in the graft epithelium and lamina propria and the proportion of CD8+ and CD25+ cells. FTY720 also significantly decreased T-cell receptors and increased B cells in the graft Peyer's patches. CONCLUSION: FTY720 promoted long-term SBTx recipient survival and maintained the architecture of intestinal allografts. FTY720 immunosuppression may be associated with a reduction of T-cell recruitment subsequent to the redistribution of lymphocyte subpopulations to control the proliferation and activation of graft-infiltrating cells in intestinal allografts.

Animals↗

PubMed2003

Ultrasonographic prediction of clinical pulmonary hypoplasia: measurement of the chest/trunk-length ratio in fetuses.

Pulmonary hypoplasia is involved in patients with various surgical diseases. The aim of this study was to evaluate the clinical usefulness of measurement of the chest/trunk-length ratio (C/T) for predicting pulmonary hypoplasia in patients with congenital anomalies, with the exception of mass-like lesions in the thorax such as diaphragmatic hernia and cystic lung diseases. For measurement of C/T on fetal ultrasound, the sagittal section of the body trunk, including the spine, was analyzed. C/T was calculated as the chest length, defined from the top of the thorax to the top of the diaphragm, divided by the trunk length, defined from the top of the thorax to the bottom of the urinary bladder. From 1986 to 2000, measurements of C/T were undertaken in 49 healthy fetuses from 17 to 37 weeks of gestation and 98 fetuses with congenital anomalies, with the exception of intra-thoracic mass lesions, omphalocele, and fetal hydrops. Pulmonary hypoplasia was clinically assessed by the following criteria: (1) a lung-to-birth-weight ratio of 0.012 or less; (2) patients who required high-frequency oscillatory ventilation with mean airway pressure of 15 cmH(2)O or more with pure oxygen and/or who died presenting respiratory failure without evidences of meconium aspiration, congenital pneumonia, sepsis or hyaline membrane disease. For a predicting value for pulmonary hypoplasia to be obtained, sensitivity, specificity, positive predictive value and negative predictive value were quoted between C/T in patients with pulmonary hypoplasia and those without pulmonary hypoplasia. Healthy fetuses revealed the mean value as 0.38+/-0.03, with no significant change after 20 weeks of gestation. Pulmonary hypoplasia was assessed in 25 fetuses with urethral atresia and stenosis, renal agenesis, polycystic kidney, cloacal anomalies, diaphragmatic eventration, bronchopulmonary foregut malformation, chest deformity, meconium peritonitis and sacrococcygeal teratoma. As a predicting value for pulmonary hypoplasia, 0.32 or less of the maximum value of C/T indicated good accuracy, with a sensitivity of 92.0%, specificity of 95.9%, positive predictive value of 88.5% and negative predictive value of 97.2%. Ultrasonic measurement of C/T is useful in predicting postnatal respiratory conditions with regard to pulmonary hypoplasia.

Abnormalities, Multiple↗

PubMed2003

Case of congenital bronchial atresia detected by fetal ultrasound.

Congenital bronchial atresia is an anomaly characterized by a mucocele associated with a blindly terminating segmental or lobar bronchus. We report on a case of congenital atresia of the left superior segmental bronchus (B6) followed by fetal ultrasonography, which showed a large simple cyst with a surrounding small echogenic area. A large cyst and persistent lung fluid in the affected segment were noted in the early neonatal period.

Adult↗

PubMed2003

Rapid progression of intrapulmonary arteriovenous shunting in polysplenia syndrome associated with biliary atresia.

This report describes a patient with biliary atresia (BA) associated with polysplenia syndrome who showed a rapid progression of intrapulmonary arteriovenous shunting (IPS), resulting in a fatal outcome. Intrauterine ultrasonography at 36 weeks of gestation revealed fetal abnormalities, including situs inversus, absent retrohepatic inferior vena cava, and azygous connection. She was diagnosed postnatally as BA because of persistent acholic stool and neonatal jaundice. She underwent hepatic portoenterostomy at age 158 days. The gallbladder and the hepatic ducts were hypoplastic, and the common bile duct was absent. Magnetic resonance image and operative findings also identified polysplenia and an absent portal trunk. Liver histology showed cirrhotic changes and bile duct proliferation. Postoperatively, she achieved good bile secretion, with gradual decrease of total bilirubin. However, she had repeated febrile episodes, and computerized tomography at age 7 months showed multiple liver cysts. Thereafter, she presented with exertional dyspnea. Contrast-enhanced echocardiography showed IPS with a degree of 2/III at age 8 months and 3/III at 10 months. (99m)Technetium-labeled macroaggregated albumin ((99m)Tc-MAA) scintigraphy revealed a shunt ratio of 25.5% at 9 months and 39.7% at 10 months. Percutaneous transhepatic drainage of the bile cysts was performed without success. Sludged bile was obtained. However, respiratory distress rapidly progressed, and she died at age 11 months. In the present patient, the association of polysplenia syndrome and absent portal vein with BA, as well as liver cirrhosis, seemed to be contributing factors to rapid progression of IPS in early life.

Abnormalities, Multiple↗

PubMed2003

Laparoscopic liver biopsy performed safely in a child with hepatic dysfunction: report of a case.

We performed laparoscopic liver biopsy in a 10-year-old girl with acute myelocytic leukemia and coagulopathy. Each biopsy was taken under laparoscopic ultrasound (LUS) guidance, and hemostasis was achieved with an argon beam coagulator (ABC). These instruments were introduced through one 10/12-mm port, which also allowed the insertion of surgical gauze for direct compression. By using LUS, ABC, and one full-sized working port, laparoscopic liver biopsy becomes a viable and safer alternative, even for children with coagulopathy.

Biopsy↗

PubMed2003

Beneficial effects of n-9 eicosatrienoic acid on experimental bowel lesions.

PURPOSE: Dietary fortification of n-9 polyunsaturated fatty acids (PUFA) or 5,8,11-eicosatrienoic acid (ETrA) as well as n-3 PUFA might contribute to the suppression of leukotriene B4 (LTB4) synthesis and thereby reduce inflammatory bowel lesions. As a result, the effect of an ETrA-enriched diet on experimental bowel lesions was examined in this study. METHODS: In Expt. 1, rats were freely fed either an ETrA-enriched or a standard diet. After 7 days of feeding, acute bowel lesions were induced by the subcutaneous injection of 10 mg/kg indomethacin. In Expt. 2, chronic bowel lesions were made by performing subcutaneous injections of 7.5 mg/kg indomethacin twice. After the first injection, the rats were freely fed either an ETrA-enriched or a standard diet for 7 days. RESULTS: In both experiments, the rats fed an ETrA-enriched diet showed increased levels of ETrA in the plasma and intestinal mucosa, and a decreased inflammation score. However, there was no significant decrease in plasma and intestinal mucosal LTB4 in the ETrA-enriched diet-fed rats. CONCLUSION: These results suggest that the dietary supplementation of ETrA may have both prophylactic and therapeutic effects on experimentally produced bowel lesions. Further investigations are necessary to clarify the effects of ETrA on bowel lesions and its mechanisms.

8,11,14-Eicosatrienoic Acid↗

PubMed2003

Esophageal motor function in congenital esophageal stenosis.

BACKGROUND/PURPOSE: Congenital esophageal stenosis (CES) is a rare condition that is associated with various foregut symptoms. The aim of the current study was to investigate esophageal motor function in pediatric patients with isolated CES. METHODS: Four boys with CES (age, 3 weeks to 4 years old) were studied before treatment. The initial symptoms were dysphagia or stridor. The CES was caused by fibromuscular stenosis (FMS) in 2, tracheobronchial remnants (TBR) in 1, and membranous diaphragm (MD) in 1. An esophagram, endoscopy, 24-hour esophageal pH monitoring, and manometry were conducted. RESULTS: The esophagram showed the stasis of contrast medium proximally to the distal esophageal narrowing in FMS/TBR patients. Endoscopic esophagitis was not found in any patients. Three patients were documented with pathologic esophageal acid exposure by 24-hour esophageal pH monitoring. Manometry showed that esophageal contractions predominantly were synchronous in FMS/TBR patients but were peristaltic in an MD patient. Basal lower esophageal sphincter (LES) pressure was at least 20 mm Hg in all. Swallow-induced LES relaxations were incomplete in FMS/TBR patients. CONCLUSIONS: The presence of gastroesophageal reflux and impaired esophageal motility are common in patients with CES.

Child, Preschool↗

PubMed2003

Sequence variants of the Axin gene in hepatoblastoma.

The Wnt signaling pathway plays critical roles in the embryonic development and tumorigenesis. As a part of the Wnt signal transduction, the function of Axin complex is inhibited, leading to accumulation of beta-catenin. In hepatoblastomas, loss of APC (adenomatous polyposis coli) function or activation of beta-catenin that are the other two components involving in Wnt signaling has been demonstrated. Because hepatoblastoma shows immunohistochemical positivity of beta-catenin more often than its mutation frequency, we analyzed the Axin gene as a candidate to lead beta-catenin accumulation in hepatoblastoma. The coding region of the Axin gene was examined by PCR-SSCP using 24 sets of the primers in 22 hepatoblastomas and some paired normal tissues. Samples revealing aberrant band patterns were subjected to direct sequencing analysis. We identified totally eight variants in the exons and four intronic nucleotide substitutions. Seven variants in the exons were silent mutations, however, the remaining variant at codon 95 (ACG-->ATG) found in one hepatoblastoma predicted to result in an amino acid change from threonine to methionine. The paired peripheral blood DNAs from this patient also showed the same change; we suggested that it was a germline mutation of Axin gene. Our results suggest that mutation of the Axin gene may have a tumorigenic function in a subset of childhood hepatoblastomas.

Journal Article↗

PubMed2003

Fetal mesenchymal hamartoma of the liver: report of a case.

The authors report a case of hepatic mesenchymal hamartoma diagnosed prenatally with ultrasound scan and magnetic resonance imaging (MRI) and confirmed histologically postdelivery. The fetus had a multicystic mass in the left upper abdomen, which showed a rapid enlargement accompanying maternal hypertension and preterm labor. The patient was delivered by cesarian section at 30 weeks and 5 days weighing 1,190 g, and, at birth, a large abdominal mass and severe anemia were noted. Surgical resection and neonatal management were successful, and the patient is alive in a good condition after 3 years follow-up. Although histologically benign, because this lesion frequently results in perinatal complications such as fetal hydrops, maternal toxemia, and preterm labor, early careful fetal ultrasonography should improve the prognosis of this lesion.

Adult↗

PubMed2003

Laparoscopically assisted surgery for congenital gastric or duodenal diaphragm in children.

Presented are our recent experiences with successful laparoscopically assisted surgery in two children with congenital gastric or duodenal diaphragm. Laparoscopy was used as an adjunct in performing the following surgical procedures: (1) inspection of the entire bowel, (2) identification and evaluation of the involved site, and (3) mobilization and exteriorization of the involved site. A minimal transverse incision was made for exteriorization. Extracorporeal removal of the diaphragm was followed by pyloroplasty or duodenoplasty. Each patient had a rapid and uncomplicated recovery with complete resolution of the symptoms. Laparoscopically assisted surgery may be a valuable modality in pediatric patients with congenital gastric or duodenal diaphragm. It allows better assessment of the entire bowel, minimizing the disfiguring and morbid abdominal incisions, without impeding the effectiveness of the planned operation. Avoidance of full-scale laparotomy may decrease the risk of future adhesions. These advantages seem attractive especially for children with longer life expectancy.

Child↗

PubMed2003

Mutation of beta-catenin and its protein accumulation in solid and cystic tumor of the pancreas associated with metastasis.

Beta-catenin serves not only as a structural component of the E-cadherin-mediated cell-cell adhesion system, but also as a signaling molecule of the Wnt/wingless pathway. Mutations of beta-catenin and aberrant expression of its protein have been identified in a number of different types of human malignancies. To determine the role of beta-catenin in solid and cystic tumor (SCT) of the pancreas, a rare neoplasm usually observed in young females, we examined three primary tumors and one corresponding liver metastatic tumor presented in pediatric patients. Single strand conformation polymorphism and neucleotide sequencing analysis confirmed a TCT right curved arrow TTT somatic mutation at codon 37 changing serine to phenylalanine in one of the primary tumors and its corresponding metastatic tumor. Immunohistochemical analysis displayed abnormally strong nuclear and widespread cytoplasmic expression of beta-catenin in these tumors with the mutation. Our observations suggest that, in some SCTs of the pancreas presented in the pediatric age group, mutated beta-catenin has an important oncogenic effect.

Child↗

PubMed2002

Collis-Nissen procedure in patients with esophageal atresia: long-term evaluation.

A subset of patients with esophageal atresia (EA) have an associated short esophagus and require an antireflux procedure. The Collis-Nissen procedure, which consists of a combination of Collis gastroplasty and Nissen fundoplication, is considered an option in such conditions. The long-term results of EA patients undergoing this procedure have rarely been reported. The results of the Collis-Nissen procedure were examined in four EA patients with follow-up for an average of 9 years. The Collis-Nissen procedure was conducted concurrently with segmental esophageal resection for an associated congenital esophageal stenosis close to the esophagogastric junction in two postoperative Gross type C patients (7 months, 2 years), as an antireflux operation in a postoperative Gross type A patient with an unreducible sliding hiatal hernia (10 years), and with primary repair of EA in a Gross type A patient with a long gap (4 months). There were no significant complications except minor anastomotic leakage and an anastomotic stenosis that required postoperative dilation. Significant reflux was negative, as shown by an upper gastrointestinal study and scintigraphy. Limited esophagitis just above the esophagogastric junction was observed in a Gross type A patient with a long mediastinal gastric segment. Swallow-related pressure reduction at the wrapping cuff was detected by manometric examination. The Collis-Nissen procedure is a useful option for treating EA patients who require esophageal lengthening and control of gastroesophageal reflux.

Esophageal Atresia↗

PubMed2002

Amino acid transport in a human neuroblastoma cell line is regulated by the type I insulin-like growth factor receptor.

Insulin-like growth factor I (IGF-I) and IGF-II stimulate cancer cell proliferation via interaction with the type I IGF receptor (IGF-IR). We put forward the hypothesis that IGF-IR mediates cancer cell growth by regulating amino acid transport, both when sufficient nutrients are present and when key nutrients such as glutamine are in limited supply. We examined the effects of alphaIR3, the monoclonal antibody recognizing IGF-IR, on cell growth and amino acid transport across the cell membrane in a human neuroblastoma cell line, SK-N-SH. In the presence of alphaIR3 (2 micro/ml), cell proliferation was significantly attenuated in both control (2 mM glutamine) and glutamine-deprived (0 mM glutamine) groups. Glutamine deprivation resulted in significantly increased glutamate (system X(AG)(-)), MeAIB (system A), and leucine (system L) transport, which was blocked by alphaIR3. Glutamine (system ASC) and MeAIB transport was significantly decreased by alphaIR3 in the control group. Addition of alphaIR3 significantly decreased DNA and protein biosynthesis in both groups. Glutamine deprivation increased the IGF-IR protein on the cell surface. Our results suggest that activation of IGF-IR promotes neuroblastoma cell proliferation by regulating trans-membrane amino acid transport.

Amino Acids↗

PubMed2002

Zoom endoscopic evaluation of rejection in living-related small bowel transplantation.

BACKGROUND: This study evaluated zoom endoscopic findings according to four components in comparison with the histologic findings of acute cellular rejection (ACR) in a living-related small bowel transplantation (SBTx) patient. METHODS: A 16-year-old boy with microvillus inclusion disease underwent SBTx with a 150-cm-long ileal graft from a blood-identical living-related donor. The endoscope was inserted into the distal stoma of the graft, and the mucosal architecture was observed under zoom. The observed findings were expressed by the following four components and graded as 0 to 2: H, homogeneity of mucosal change, minimal (H-0), patchy (H-1), diffuse (H-2); V, appearance of villi, stringlike (V-0), tonguelike (V-1), domelike (V-2); W, widening of crypt area, narrow (W-0), slightly widened within a width of one villus (W-1), markedly widened beyond a width of one villus (W-2); E, erythema in crypt area: no redness (E-0), sporadic erythema (E-1), diffuse erythema (E-2). RESULTS: Histologic ACR was grade 0 in 27, grade 1 in 6, grade 2 in 3, and grade 3 in 0 occasions during 11 months after SBTx. In grade 0, 1, and 2 histology, H-0/H-1/H-2 was 85.2%/14.8%/0%, 33.3%/66.7%/0%, and 0%/100%/0%, respectively, with a significant difference among the groups by grade (P<0.05). V-0/V-1/V-2 was 48.1%/51.9%/0%, 0%/100%/0%, and 0%/66.7%/33.3% (P<0.05), W-0/W-1/W-2 was 85.2%/14.8%/0%, 0%/100%/0%, and 0%/66.7%/33.3% (P<0.05), and E-0/E-1/E-2 was 100%/0%/0%, 66.7%/33.3%/0%, and 0%/100%/0% (P<0.05), respectively. CONCLUSION: Zoom endoscopic findings, graded on four components, may reflect the histologic severity of ACR and minimize the performance of biopsies in SBTx.

Adolescent↗

PubMed2002

Deficits of spatial working memory in chronic schizophrenia.

This study tests the hypothesis that deficits of spatial working memory are an inherent trait in schizophrenic patients, regardless of their clinical status. The participants were 22 chronic schizophrenic patients, 11 schizophrenic patients in remission, and 22 normal adults. All participants were asked to track the outlines of a square presented on a computer screen in a clockwise direction while moving their eyes at their preferred rate and then to reproduce the square on a blank computer screen (Task A). Thereafter, the computer only displayed the four corners of the same square. The corners were displayed sequentially in a clockwise direction, one at a time at equal intervals. They were asked first to track the four corners of the square and then to reproduce the square on a blank computer screen (Task B). Chronic schizophrenic patients reproduced tasks A and B with significantly greater distortions than normal controls. The extent of their distortions was significantly greater during the reproduction of Task A than Task B. By contrast, schizophrenic patients in remission reproduced both Tasks A and B with the same accuracy as normal controls. On the basis of these findings it is concluded that the chronic schizophrenic patients have a significant deficit of spatial working memory, but that this deficit can be ameliorated by cognitive interventions and is therefore not an immutable trait in schizophrenia.

Adult↗

PubMed2002

Mutation analysis of the BCL10 gene in childhood solid malignancies.

BACKGROUND: BCL10, a gene involved in apoptosis signaling, has recently been identified at chromosome 1p22. This gene was found to be mutated in several types of lymphomas and other kinds of solid tumors. Especially in hepatocellular carcinoma, high mutation rates have been reported. These findings suggest that its inactivation may play an important pathogenetic role in tumorigenesis. Furthermore, abnormalities of chromosome 1 where the BCL10 gene is located are a common feature in pediatric solid tumors. Therefore, we analyzed 95 pediatric solid cancers for genomic BCL10 mutations. PROCEDURE: Three exons, which encode the whole coding region, were examined in 95 tumor tissues by PCR-SSCP method. Samples revealing aberrant band patterns were subjected to direct sequencing analysis. RESULTS: A total of six nucleotide changes were detected. Two were in intron 1 (IVS1 + 11C > G, IVS1 + 58G > C) and four were in exons 1 or 3 (Ala5Ser, Leu8Leu, Thr162Met and Gly213Glu). Of four exonic changes, three at codons 5, 162, and 213 resulted in amino acid substitution. In non-tumor tissues, however, similar mutation types were found, suggesting that all nucleotide changes detected were genetic polymorphisms. CONCLUSIONS: This study represents the first genetic analysis of the BCL10 gene in pediatric solid malignant tumors. Our results suggest that BCL10 mutation as a mechanism involved in tumorigenesis is unlikely to be associated with most childhood malignancies.

Child↗

PubMed2002

Recent advances in pathophysiology and surgical treatment of congenital dilatation of the bile duct.

The introduction of the concept of pancreaticobiliary maljunction (PBM) has led to significant progress in the pathogenetic study and surgical treatment of congenital dilatation of the bile duct (CDBD). Clinical studies of 155 patients with CDBD, and basic experimental studies of the mechanisms of bile duct dilatation and associated pancreatitis were conducted. The CDBD was morphologically classified as either cystic or cylindrical type. Clinical signs, symptoms, and laboratory findings were highly dependent on two factors: the age at onset and the reflux of pancreatic juice into the bile duct through the PBM. The canine experimental model of PBM exhibited not only significant bile duct dilatation but also morphological findings similar to those in the CDBD patients. Subsequent studies in a rat model clarified the involvement of activated pancreatic enzyme phospholipase A(2) in PBM-associated pancreatitis. For surgical treatment, cystoenterostomy has been superseded by hepatico-enterostomy after removal of the damaged bile ducts and blocking their communication with the pancreatic duct. Long-term follow-up studies have shown excellent results by confirming the surgical correction based on the pathological principles. Regarding biliary reconstruction, jejunal interposition hepatico-duodenostomy, which is, theoretically, a logical approach was unexpectedly shown to often lead to bile reflux gastritis, so it is now superseded by Roux-en-Y hepaticojejunostomy.

Adolescent↗

PubMed2002

Gut glutamine metabolism at different stages of sepsis in rats.

PURPOSE: To investigate gut glutamine metabolism and determine the effects of glutamine supplementation in different stages of sepsis in a rat model. METHODS: Sepsis was induced by cecal ligation and puncture (CLP), and control rats underwent a sham operation. In the first experiment, a continuous infusion of normal saline was started at the end of the operation. Intestinal blood flow, glutamine concentrations of the abdominal aorta and superior mesenteric vein (SMV) were measured, and gut glutamine extraction and flux were calculated 5 h after the sham operation, and 5 and 20 h after CLP, being groups Ia ( n = 9), Ib ( n = 8), and Ic ( n = 8), respectively. In the second experiment, animals received a continuous infusion of alanyl-glutamine instead of normal saline and were divided into groups IIa ( n = 8), IIb ( n = 8), and IIc ( n = 6). The same parameters were measured in each group and compared with those of the corresponding group in the first experiment. RESULTS: In the first experiment, no significant difference in SMV blood flow was seen among the groups. The arterial glutamine concentration was increased in group Ic ( P < 0.05) compared with that in groups Ia and Ib. Gut glutamine extraction was significantly increased in group Ib ( P < 0.01) and significantly decreased in group Ic ( P < 0.05) compared with that in group Ia. In the second experiment, gut glutamine flux was significantly increased in group Ilb ( P < 0.01) compared with that in group Ib, but the increase did not reach statistical significance between groups Ia and IIa or between groups Ic and IIc. CONCLUSION: These results indicate that intestinal glutamine uptake is increased and glutamine utilization is enhanced by glutamine supplementation in early sepsis.

Animals↗