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Biomedical subjects

A Okada

Publications and source records attributed to A Okada.

At least 55 records · Page 3Linked to original sources
PubMed2001

Insulin-like growth factor-I stimulates amino acid transport in a glutamine-deprived human neuroblastoma cell line.

It is still unknown how insulin-like growth factor-I (IGF-I) regulates cancer cell growth in the condition of the limited availability of key nutrients, such as glutamine. We investigated the effects of IGF-I on cell growth and amino acid transport in a glutamine-deprived human neuroblastoma cell line, SK-N-SH. Cell growth was measured, and 3H-labeled amino acid transport was assayed after treatment with or without IGF-I (50 ng/ml) in 2 mM (control) and 100 microM glutamine concentrations. Cell growth rates were dependent on glutamine concentrations. IGF-I stimulated cell growth in both 2 mM and 100 microM glutamine. IGF-I stimulated glutamine transport in 100 microM glutamine with the mechanism of increasing carrier Vmax, but had no effect in 2 mM glutamine. IGF-I also stimulated leucine, glutamate and 2-(methylamino)isobutyric acid transport in 100 microM glutamine. There were significant increases in [3H]thymidine and [3H]leucine incorporation in IGF-I-treated cells in both 2 mM and 100 microM glutamine. These data suggest that IGF-I stimulates cell growth by increasing amino acid transport in the condition of low glutamine levels in a human neuroblastoma cell line. This mechanism may allow to maintain cell growth even in nutrient-deprived tumor tissues.

Amino Acids↗
PubMed2001

Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis.

Vascular endothelial growth factor (VEGF) and its two receptors, Fms-like tyrosine kinase 1 (Flt-1) (VEGFR-1) and KDR/Flk-1 (VEGFR-2), have been demonstrated to be an essential regulatory system for blood vessel formation in mammals. KDR is a major positive signal transducer for angiogenesis through its strong tyrosine kinase activity. Flt-1 has a unique biochemical activity, 10-fold higher affinity to VEGF, whereas much weaker tyrosine kinase activity compared with KDR. Recently, we and others have shown that Flt-1 has a negative regulatory function for physiological angiogenesis in the embryo, possibly with its strong VEGF-trapping activity. However, it is still open to question whether the tyrosine kinase of Flt-1 has any positive role in angiogenesis at adult stages. In this study, we examined whether Flt-1+ could be a positive signal transducer under certain pathological conditions, such as angiogenesis with tumors overexpressing a Flt-1-specific, VEGF-related ligand. Our results show clearly that murine Lewis lung carcinoma cells overexpressing placenta growth factor-2, an Flt-1-specific ligand, grew in wild-type mice much faster than in Flt-1 tyrosine kinase domain-deficient mice. Blood vessel formation in tumor tissue was higher in wild-type mice than in Flt-1 tyrosine kinase-deficient mice. On the other hand, the same carcinoma cells overexpressing VEGF showed no clear difference in the tumor growth rate between these two genotypes of mice. These results indicate that Flt-1 is a positive regulator using its tyrosine kinase under pathological conditions when the Flt-1-specific ligand is abnormally highly expressed. Thus, Flt-1 has a dual function in angiogenesis, acting in a positive or negative manner in different biological conditions.

Animals↗
PubMed2001

Three-dimensional pressure imaging: a novel method for intraoperative manometry during laparoscopic esophagomyotomy for esophageal achalasia.

With the introduction of computerized manometry, the creation of the three-dimensional (3-D) pressure image with measurement of pressure vector volume (PVV) has become available to assess the pressure structure of the high-pressure zone (HPZ) of the distal esophagus. We have applied this technique to intraoperative manometry during laparoscopic surgery for esophageal achalasia (EA). A laparoscopic esophagomyotomy with anterior fundoplication was performed in a 12-year-old boy with EA. Computerized 3-D images were obtained by a stepwise pullback of a manometric assembly with eight radial side-holes to quantitate the PVV of the HPZ of the distal esophagus in each stage of the operation for EA. Virtual abolishment of the peak pressure image and a marked reduction in the PVV after esophagomyotomy suggested appropriate decompression of the HPZ. Intraoperative manometry using computerized 3-D pressure imaging with measurement of the PVV is thus useful to assess the HPZ during laparoscopic surgery for EA.

Child↗
PubMed2001

High frequency of beta-catenin mutations in hepatoblastoma.

Hepatoblastoma (HB) is an embryonic neoplasm representing the most frequent malignant liver tumour in childhood. Its tumourigenesis at the molecular level is still poorly understood, and candidate genes are yet to be identified. According to recent reports describing beta-catenin mutations (BCM) at hot-spot regions involving exon 3 in several types of malignancies including HB, we investigated BCM in 16 HBs classified into different histological types. One tumour had been previously confirmed to harbour adenomatous polyposis coli (APC) mutations that exhibit a similar oncogenic effect to that of BCM. Mutations in both exon 3 and its flanking region of the beta-catenin gene were investigated and determined. Twelve tumours (75%) revealed pathogenic BCM, including 5 with missense mutations at codons 32, 34, or 37 and 7 with interstitial deletions that partially or totally affected exon 3. All 7 deletions were in-frame deletions without frameshift. A single nucleotide change at codon 31 regarded as non-pathogenic polymorphism was detected in the tumour possessing APC mutations. Therefore, a total of 13 tumours (81%) were compromised by an enhanced beta-catenin-mediated transcription pathway. Mutations were observed in every histological type of HB. The very high frequency without correlation to histological type indicates that BCM are crucial events in the tumourigenesis of HB.

Child↗
PubMed2001

Analysis of the development of normal foregut and tracheoesophageal fistula in an adriamycin rat model using three-dimensional image reconstruction.

To examine the developmental process of the normal trachea and esophagus and their maldevelopment leading to tracheoesophageal fistula (TEF), we performed three-dimensional (3-D) image reconstruction of the developing foregut in normal and adriamycin (ADM)-induced TEF rats. Microscopic images of serial sections of embryos from seven normal and 14 ADM-treated rats killed every half a day after 11-14 days' gestation were traced and reconstructed using a 3-D construction imaging system (TRI, RATOC System Engineering, Tokyo, Japan). In the normal embryos, the lung bud appeared just below the pharyngeal foregut on day 11 and it elongated caudally to shape into the trachea as they grew. A 'tracheoesophageal septum" did not emerge. In the TEF embryos, although the lung bud appeared in a similar position on day 11, the trachea and esophagus did not separate and only a common foregut tube elongated caudally, then bilateral bronchial primordia emerged directly from it. Furthermore, abnormal development of the notochord was evident, being retarded in separation from the foregut, finally descending along a more ventral course and bending sharply around the level of the bifurcation. Microscopically, less mesenchymal cellularity around the foregut was noted in the TEF embryos. The trachea seemed to be formed only by caudal elongation of the lung bud in the normal embryos. In the ADM-induced TEF embryos, the upper foregut appeared to develop only into the trachea, and this maldevelopment may be implicated in the abnormal interaction between the foregut and the surrounding mesenchyme.

Animals↗
PubMed2001

Dynamic change of cells expressing MMP-2 mRNA and MT1-MMP mRNA in the recovery from liver fibrosis in the rat.

BACKGROUND/AIMS: The aim of this study was to investigate whether both matrix metalloproteinase-2 (MMP-2) and membrane type 1 MMP (MT1-MMP) participate in the spontaneous resolution of liver fibrosis. METHODS: Transcription of both genes was examined by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH). Gelatinase activity was investigated by zymography. RESULTS: Gene expression by RT-PCR showed that both genes increased in the process of liver fibrosis, then decreased gradually in the recovery phase. ISH revealed that distribution of positive cells changed quickly in the recovery phase. Positive cells were widely seen in the liver, mainly around fibrous septa, in the aggressive phase, but were exclusively observed at the interface between the resolving fibrous band and the parenchyma, then were diffusely located in the lobules in the recovery phase. Main cells expressing both mRNAs seemed to be stellate cells for their morphology, though they did not express characteristic cell markers. Some hepatocytes and Kupffer cells expressed both mRNAs in the recovery phase. Gelatinase activity of MMP-2 increased in the recovery phase of 8-week-treated rat liver by gelatin zymography. CONCLUSIONS: The results of present study suggest that both enzymes participate in the destruction of extracellular matrix in coordination with MMP-13.

Animals↗
PubMed2001

Sequential measurement of human herpesvirus 6 DNA with polymerase chain reaction method in pediatric living-related liver transplantation.

BACKGROUND: Human herpesvirus 6 (HHV-6), a causative virus of exanthem subitum, may occasionally present with a severe clinical form in immunosuppressed patients after transplantation. In this study, HHV-6 DNA was sequentially measured with a polymerase chain reaction (PCR) method, a quick and sensitive modality in pediatric living-related liver transplantation (LTx). METHODS: Subjects consisted of 5 post-operative biliary atresia patients undergoing living-related LTx at ages from 8 months to 4 yr. Immunosuppression was performed with Tacrolimus (blood trough level 8-18 within 1 month and 5-10 ng/mL thereafter) and low-dose steroid. Specimens were peripheral blood mononuclear cells (PBMC), plasma, and liver biopsy tissue. The amount of HHV-6 DNA was semiquantified as follows: 1+, 1-10; 2+, 10-100; 3+, 100-1000; 4+, over 1000 copies/105 PBMCs. RESULTS: A total of 69 blood samples and three liver biopsies were provided for the examination. HHV-6 DNA in PBMC was positive in 2 donors and 3 recipients before LTx. Two patients with negative DNA were converted to 3+ at 2-3 wk after LTx and 3 with positive DNA remained 2+ to 3+ throughout the post-LTx period. Only 1 patient developed clinical symptoms, such as fever, liver dysfunction, petechiae, idiopathic thrombocytopenic purpura, and finally bone marrow suppression. HHV-6 DNA in the liver biopsy tissue and plasma in this patient were 4+ and 2+, respectively. CONCLUSION: HHV-6 DNA in PBMC measured by the PCR method may be persistently high in pediatric recipients after living-related LTx. Although HHV-6 DNA in PBMC may be positive in case of evident infection, positivity in PBMC may not be always associated with the clinical symptoms.

DNA, Viral↗
PubMed2001

Oral administration of tacrolimus in the presence of jejunostomy after liver transplantation.

The feasibility of oral administration of tacrolimus in the presence of an intestinal stoma after liver transplantation (LTx) has not been adequately demonstrated. A 10-month-old girl underwent LTx with biliary reconstruction using a Roux-en Y loop. She developed intestinal perforation and underwent a jejunostomy at 40-50 cm distal to the jejunojejunostomy of the Roux-en Y loop on day 8 post-LTx. Tacrolimus was given twice daily via a nasogastric tube or orally; the initial dose of tacrolimus was 0.10 mg/kg/day. Until the time of intestinal perforation, the trough level of tacrolimus ranged from 13.0 to 19.6 ng/mL. The dose-normalized trough concentration (DNTC) of tacrolimus ranged from 130 to 196 ng.kg.day per mg.mL (control: 80-145 ng.kg.day per mg.mL). For a 2-week period when the patient was septic, the tacrolimus dose was reduced to 0.05 mg/kg/day, with a subsequent trough level of 3.6-5.1 ng/mL (DNTC: 72-102 ng.kg.day per mg.mL). After 3 weeks, the dose was increased to 0.175 mg/kg/day with the disappearance of infection; the trough level ranged from 8.5 to 9.7 ng/mL with a peak level of 26.3 ng/mL (DNTC: 48.5-55.4 ng.kg.day per mg.mL). After the initiation of oral feeding, the dose was slightly increased to 0.20 mg/kg/day with the trough level ranging from 8.1 to 9.8 ng/mL (DNTC: 40.5-49 ng.kg.day per mg.mL). After closure of the jejunostomy, the dose of tacrolimus was reduced to 0.075 mg/kg/day to maintain the same trough level (7.9-9.1 ng/mL) and the DNTC ranged from 105 to 121 ng.kg.day per mg.mL. In conclusion, oral administration of tacrolimus may achieve the therapeutic level, even in the presence of jejunostomy after LTx, although the bioavailability is decreased.

Administration, Oral↗
PubMed2001

Histopathologic changes after tracheobronchial reconstruction with costal cartilage graft for congenital tracheal stenosis.

BACKGROUND/PURPOSE: Congenital tracheal stenosis is an uncommon, life-threatening condition. Recently, tracheoplasty using costal cartilage grafts to enlarge the lumen was used successfully in such cases. In this study, we evaluated postoperative changes of costal cartilage grafts after tracheoplasty. METHODS: Costal cartilage patch tracheoplasty was used for surgical correction of long-segment congenital tracheal stenosis in 18 infants. Six patients whose tracheal specimens were obtained at autopsy are included in this study. The mean age at the time of repair was 4.8 months, and the mean period after operation was 7.5 months. Cartilage graft survival and epithelialization of inner layer was evaluated in each case. RESULTS: The mean width and length of grafts was 6.3 x 35 mm at operation and 4.0 x 22 mm at autopsy. The graft size was diminished gradually after operation and was replaced completely by mature scar tissue 2 years after operation. However, diameter of the reconstructed site was not reduced. Reepithelialization of the graft site with ciliated columnar epithelium was found in every case. Chondrocyte numbers were reduced and remaining cartilage was rather eosinophilic, suggesting that the degenerative process was ongoing in the graft. CONCLUSIONS: The costal cartilage grafts established a functional tracheal lumen, and reepithelialization with ciliated columnar epithelium was found at the graft site. The costal cartilage grafts continues to be an important option as graft material for tracheal reconstruction in infants with long segment congenital tracheal stenosis.

Cartilage↗
PubMed2001

Operative management for sacrococcygeal teratoma diagnosed in utero.

BACKGROUND/PURPOSE: Sacrococcygeal teratomas (SCT) diagnosed in utero have been reported to be large and associated with high perinatal mortality rate. However, operative management including timing of operation after birth, combined abdominal approach for devascularization, and the position of the patients during resection is not well established. METHODS: A retrospective review of 14 patients with SCT between 1978 and 1999 was performed. To prevent massive bleeding during surgery, the authors used an abdominoperineal resection in the supine position after devascularization. The patients' clinical and sonographic characteristics, prenatal outcome, operative management, and postnatal outcomes were examined. RESULTS: One fetus died in utero. Two patients died within a week, but no late death and no malignant degeneration were noted. A staged operation with devascularization was performed in 2 patients, and 1 death occurred. Surgical management was analyzed between survivors without massive bleeding at surgery (n = 9) and others (n = 4). A significant difference was observed in the subgroup of tumor resection with devascularization or supine position and that of early resection with devascularization or supine position. CONCLUSIONS: Early resection using the abdominoperineal approach supported by close antenatal sonography may be preferable for a favorable outcome. Resection in the supine position after devascularization may have advantages of respiratory management, cardiac resuscitation, and bleeding prevention. J Pediatr Surg 36:545-548.

Female↗
PubMed2001

Clinicopathologic relationship of hypoganglionosis.

BACKGROUND/PURPOSE: Congenital motor dysfunction of the intestine associated with a morphologically abnormal myenteric nervous plexus (MP) is known as Hirschsprung's disease allied disorder (HAD). However, the clinicopathologic features of HAD are not well understood, partially because a standardized method of histologic evaluation of MP has not been established. To elucidate the clinicopathologic relationship of HAD the authors reviewed 6 cases of HAD using a newly devised histologic evaluation method. METHODS: Flat-mounted frozen sections of the ileum were stained for S-100 protein by fluorescent immunohistochemistry. Quantitative evaluation of MP was performed by measuring the fluorescence-positive area (MP ratio), and the results were compared with those of age-matched normal controls. RESULTS: All of 6 patients required laparotomy within 1 month after birth and enterostomy between 23 days and 10 months. Three died of intractable enteritis by the age of 2.2 years and were totally dependent on parenteral nutrition (PN) throughout their lives. The other 3 have survived for 6 to 10 years but have required PN occasionally. MP ratio in controls was more than 0.34 at all ages, whereas that in HAD was significantly lower than that in controls according to the clinical severity. CONCLUSION: MP size measured on 2-dimensional demonstration is suggested to be an indicator of clinical severity of HAD. J Pediatr Surg 36:898-900.

Case-Control Studies↗
PubMed2001

Plasma endothelin-1 level as a marker reflecting the severity of portal hypertension in biliary atresia.

BACKGROUND/PURPOSE: The aim of this study was to examine if the plasma endothelin-1 (ET-1), a potent vasoconstrictor, level may reflect the severity of portal hypertension associated with liver cirrhosis in biliary atresia (BA). METHODS: Forty-eight postoperative BA patients aged 6 months to 20 years were studied. Plasma ET-1 was measured by a sandwich method of enzyme immunoassay. ET-1 was compared with Child's score and laboratory data. ET-1 levels were compared among groups of patients with various degrees of histologic fibrosis and portal hypertension. RESULTS: Plasma ET-1 was 5.3 +/- 3.5 pg/mL in BA, higher than in controls (3.1 +/- 0.8, n = 27; P <.05). ET-1 correlated with Child's score, serum total bilirubin, direct bilirubin, aspartate aminotransferase, albumin, prothrombin time, hepaplastin test, fibrinogen, cholinesterase, total cholesterol, Fischer's molar ratio, prealubumin, and hyaluronic acid, respectively (P <.05). ET-1 also correlated with the severity of histologic fibrosis, gastroesophageal varices, the presence of splenomegaly, ascites, venous dilatation on the abdominal wall, or pulmonary vascular abnormalities. In 4 patients undergoing liver transplantation (LTx), ET-1 after LTx was lower than that before LTx (P <.05). CONCLUSION: Plasma ET-1 level may be a useful index reflecting the severity of cirrhosis and portal hypertension in BA.

Adolescent↗
PubMed2001

Motor abnormality in the gastroduodenal junction in patients with infantile hypertrophic pyloric stenosis.

BACKGROUND/PURPOSE: Periodic clusters of phasic pressure waves in the gastroduodenal junction (GDJ) have been seen in patients with infantile hypertrophic pyloric stenosis (IHPS). This study investigated the details of these pressure waves in relation to disturbed transpyloric flow in IHPS. METHODS: Manometric study was performed in 11 IHPS patients before and after atropine therapy and 2 non-IHPS infants. Pressure changes in the GDJ were measured with an 8-channel sleeve or a 9-channel sidehole micromanometric assembly under fluoroscopic control for 2 hours. RESULTS: Clusters of phasic pressure waves (365 +/- 42 mm Hg) associated with an increase in basal pressure (10 +/- 3 mm Hg) were intermittently observed in the GDJ in all IHPS patients. Similar observations were not made in the non-IHPS infants. Most antral pressure waves occurred simultaneously with those pressure waves in the GDJ in the IHPS patients. Atropine (0.01 mg/kg) transiently abolished the phasic and tonic pressure waves for 19 +/- 10 minutes. Significantly fewer phasic pressure waves were observed after atropine therapy. CONCLUSIONS: Characteristic phasic and tonic contractile activity in the GDJ is uncoordinated with the antral contractions in IHPS patients. Such incoordination may be an important factor in the disturbed transpyloric flow in IHPS.

Atropine↗
PubMed2001

Pectus excavatum repair using a costal cartilage graft for patients with tracheobronchomalacia.

BACKGROUND: Pectus excavatum is sometimes associated with tracheobronchomalacia, which usually manifests left mediastinal shift, atelectasis of the left lung, and recurrent pulmonary infection. Standard repair of pectus excavatum alone usually failed to improve symptoms. METHODS: Pexis of the great vessels and pericardium combined with the support of the lower sternum, using a contralateral costal cartilage graft following the standard Ravitch's repair of pectus excavatum, has been used in 6 children during the past 5 years. In addition to respiratory symptoms, diagnosis of tracheobronchomalacia was made by bronchoscopy using an ultrathin fiberscope. RESULTS: Using the described operative technique, an excellent cosmetic and functional result was obtained in 5 of 6 children. However, atelectasis of the left lower lobe and the narrowing of the left mainstem bronchus continued postoperatively in one patient, which required the insertion of the Palmaz stent in the left mainstem bronchus. CONCLUSION: This technique may help improve tracheobronchomalacia in patients with pectus excavatum and should be tried before the insertion of an internal stent.

Cartilage↗
PubMed2001

Cryopreservation-induced acrosomal vesiculation in live spermatozoa from cynomolgus monkeys (Macaca fascicularis).

BACKGROUND: Cryopreserved spermatozoa are known to undergo accelerated capacitation and require a shorter incubation time for fertilization. However, details of their acrosomal membranes following cryopreservation remain unclear. METHODS: Percoll density gradient centrifugation was used to remove dead spermatozoa; thus >90% live spermatozoa were recovered after cryopreservation, and acrosomal status was compared among non-incubated and incubated fresh and cryopreserved spermatozoa. RESULTS: Transmission election microscopy (TEM) using microwave methods and fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA) staining revealed that 21.1 and 61.6% respectively of non-incubated, cryopreserved spermatozoa were intact, whereas 97.6% (TEM) or 91.9% (FITC-PSA) of non-incubated fresh spermatozoa were intact. TEM revealed that 28.8% of the cryopreserved spermatozoa were swollen, and probably included among those counted as intact by FITC-PSA staining. The non-incubated cryopreserved spermatozoa had fused plasma and outer acrosomal membranes, and 36.4% of them had vesiculation when observed by TEM. FITC-PSA staining indicated that 22% of the live spermatozoa were acrosome reacted. CONCLUSIONS: Acceleration of the acrosome reaction was evident by both TEM and FITC-PSA. Incubation of cryopreserved spermatozoa for 2 h accelerated vesiculation to a state similar to that of fresh spermatozoa that had been incubated for 8 h. These results reveal that in cryopreserved spermatozoa, the process of acrosome reaction begins before incubation.

Acrosome↗