Biomedical subjects

Yutaka Hayashi

Publications and source records attributed to Yutaka Hayashi.

At least 19 recordsLinked to original sources

PubMed2007

Reciprocal expression of CCAAT/enhancer binding proteins alpha and beta in hepatoblastomas and its prognostic significance.

Hepatoblastoma is one of the common pediatric solid tumors with frequent mutation of the beta-catenin gene which might be an early event of its carcinogenesis. However, the detailed molecular mechanism is still unknown. We studied the expression levels of CCAAT/enhancer binding protein alpha (C/EBPalpha) and C/EBPbeta, which regulate differentiation and growth of embryonic hepatocytes, to establish whether or not they were involved in affecting the clinical behavior of hepatoblastoma. The quantitative real-time reverse transcriptase-PCR revealed that expression of C/EBPalpha mRNA was significantly up-regulated in tumors 223% (p=0.013) as compared with that in adjacent normal livers, while expression of C/EBPbeta was down-regulated to 27% (p=0.002). Of interest, the immunohistochemical analysis showed that expression of C/EBPalpha was higher and that of C/EBPbeta lower in the poorly differentiated tumor cells than in the well-differentiated cells within the same tumor. Furthermore, high expression of C/EBPalpha (p=0.047) as well as low expression of C/EBPbeta (p=0.025) was significantly associated with poor prognosis of the patients. Cox hazard model suggested that expression of C/EBPalpha and that of C/EBPbeta were independent indicators to predict the prognosis from age but not from histology. Thus, expression of C/EBP proteins may play an important role in the genesis and clinical behavior of hepatoblastoma probably by inducing different stages of arrest of differentiation.

CCAAT-Enhancer-Binding Protein-alpha↗

PubMed2006

Functional analysis of eubacterial ent-copalyl diphosphate synthase and pimara-9(11),15-diene synthase with unique primary sequences.

We have previously cloned a DNA fragment that contained four ORFs and was confirmed to participate in viguiepinol {3-hydroxypimara-9(11),15-diene} biosynthesis by a heterologous expression experiment, from Streptomyces sp. strain KO-3988. Of the four ORFs, ORF2 and ORF4 were confirmed to encode an ent-CDP synthase and a GGDP synthase, respectively, by experiments using recombinant enzymes. In this study, ORF3, that did not show similarities with any other known proteins was expressed in Escherichia coli and used for functional analysis. The purified ORF3 product clearly converted ent-CDP into PMD. Since ORF2 and ORF3 are the first examples of enzymes with these biosynthetic functions from prokaryotes, enzymatic properties of both enzymes were investigated. ORF2 is likely to be a dimer and requires a divalent cation such as Mg2+ and Zn2+ for its activity. The optimum pH and temperature were 5.5 and 35 degrees C. The Km value was calculated to be 13.7 +/- 1.0 microM for GGDP and the kcat value was 3.3 x 10(-2)/sec. ORF3 is likely to be a monomer and also requires a divalent cation. The optimum pH and temperature were 7.0 and 30 degrees C. The Km value for ent-CDP was estimated to be 2.6 +/- 0.2 microM and the kcat value was 1.4 x 10(-3)/sec.

Alkyl and Aryl Transferases↗

PubMed2006

Intestinal transplantation for short bowel syndrome secondary to gastroschisis.

BACKGROUND/PURPOSE: Gastroschisis is the most frequent cause of pediatric intestinal transplantation. This study reviews our experience of intestinal transplantation secondary to gastroschisis to elucidate those factors affecting the outcome of children with short bowel syndrome. METHODS: A retrospective review was performed for children who underwent intestinal transplantation for gastroschisis at the University of Miami between June 2003 and August 1994. RESULTS: Thirty-two transplants were performed in 28 children with gastroschisis during the study period. Associated intestinal anomalies were present in 22 infants (atresia [n = 14], volvulus [n = 3], and/or ischemia [n = 16]). Spontaneous prenatal closure of gastroschisis, a rare anomaly associated with bowel atresia and ischemia because of a very small abdominal defect, was seen in 9 patients. Most of the patients had a complicated course and required multiple abdominal surgeries before transplant. Fifteen (53.6%) patients are currently alive at a median follow-up of 23.5 months. Short-term survival rate has significantly improved in recent years. CONCLUSIONS: Patients with complex gastroschisis and intestinal anomalies have a significant risk for progression to short bowel syndrome. Intestinal transplantation can be a lifesaving option and provides a satisfactory outcome for children with short bowel syndrome secondary to gastroschisis.

Child↗

PubMed2006

Long-term outcome in type I biliary atresia.

PURPOSE: This retrospective study reviews the long-term outcome of type I biliary atresia (BA). METHODS: Three hundred twenty-three patients with BA, including 50 with type I, underwent corrective surgery. The surgical results, role of cholangiograms during the corrective surgery, late complications, and current statuses were evaluated. RESULTS: The overall survival rate of the nontransplant type I patients was better than that of the type II/III patients (52% vs 33%, P = .0009). Cholangiograms of 32 patients were classified into 3 types: cloudy (48%), treelike (13%), and mixed (39%). Of 26 patients who underwent corrective surgery in 1972 or later, 7 (50%), 7 (78%), and 3 (100%) patients of the cloudy type, mixed type, and treelike type, respectively, have survived without liver transplantation (LTx). Of 18 type I patients who survived more than 20 years without LTx, 7 developed severe late complications. Two of them eventually required LTx after 20 years old. CONCLUSIONS: Use of cholangiograms during corrective surgery might have a long-term prognostic value. The overall survival rate of type I BA was better than that of type II/III. The incidence of late complications was, however, considerably high in the type I survivors. All patients required careful long-term follow-up.

Anastomosis, Surgical↗

PubMed2006

Review of 86 patients with myelodysplasia and neurogenic bladder who underwent sigmoidocolocystoplasty and were followed more than 10 years.

PURPOSE: We reviewed the long-term outcome of sigmoidocolocystoplasty. MATERIALS AND METHODS: The records of 86 patients who underwent sigmoidocolocystoplasty with a followup of more than 10 years were reviewed, focusing on histopathology, renal function, vesicoureteral reflux, bladder stones and urinary continence. We developed a urinary continence evaluation score, calculated as the postoperative minus the preoperative urinary continence score, including 0-incontinence, 1-severe leakage, 2-moderate leakage, 3-mild leakage, 4-almost dry and 5-dry, for patient self-assessment of urinary continence. A score of 2 or more meant improvement and a score of less than 2 meant no improvement. RESULTS: Mean followup was 13.1 years (range 10 to 21). Histopathology showed inflammation in all cases, hyperplasia in 9 and metaplasia in 4. In 80 of 86 cases creatinine clearance was normal. Ureteral reimplantation had been performed before sigmoidocolocystoplasty in 9 cases (13 kidneys) for grades III to V vesicoureteral reflux, which recurred as grade I in 1 (1 kidney). Ureteral reimplantation was performed during sigmoidocolocystoplasty in 31 cases (58 kidneys) and grades I to II vesicoureteral recurred in 5 (6 kidneys). Of the remaining 44 sigmoidocolocystoplasty cases there were 2 (2 kidneys) of grade I vesicoureteral reflux. On (99m)technetium-dimercapto-succinic acid scintigraphy there was increased renal scarring in 8 cases. Bladder stones were identified in 18 of 86 cases during followup but they were absent at review. The urinary continence evaluation score showed improvement in 61 cases and no improvement in 25. CONCLUSIONS: Our results suggest that sigmoidocolocystoplasty is safe and effective in the long term.

Adolescent↗

PubMed2006

Living-related intestinal transplantation for a patient with hypoganglionosis.

A 14-yr-old boy with total parenteral nutrition-dependent short-bowel syndrome associated with hypoganglionosis underwent the LR-IT by using a 150 cm segment of distal ileum taken from a healthy donor. The graft vessels were connected to infrarenal aorta and inferior vena cava. The immunosuppressive regimen consisted of daclizumab, tacrolimus, and steroid. The graft surveillance for ACR was accomplished using zoom endoscopy and mucosal biopsy. The blood trough level of tacrolimus was maintained between 20 and 25 ng/mL for the first 2 months, followed by 15-20 ng/mL thereafter. The 50 mg of daclizumab was administered on the day of operation, and same dosage was repeated at 2-wk intervals. The first ACR occurred on POD-9 and was progressive, and required a 14-day course of OKT-3 injection. After the treatment with OKT-3, the graft recovered from the ACR, and began to function well enough to discontinue the intravenous nutrition on POD-55. No infectious complication has occurred. The patient was discharged in POD-112, and currently tolerates full oral intake without requiring intravenous nutritional or fluid supplementation. The donor was discharged without any complications. The LR-IT could successfully be performed with minimal risk to the donor, and it can be a treatment of choice for patients with short-gut syndrome associated with hypoganglionosis.

Adolescent↗

PubMed2006

Biosynthesis of a natural polyketide-isoprenoid hybrid compound, furaquinocin A: identification and heterologous expression of the gene cluster.

Furaquinocin (FQ) A, produced by Streptomyces sp. strain KO-3988, is a natural polyketide-isoprenoid hybrid compound that exhibits a potent antitumor activity. As a first step toward understanding the biosynthetic machinery of this unique and pharmaceutically useful compound, we have cloned an FQ A biosynthetic gene cluster by taking advantage of the fact that an isoprenoid biosynthetic gene cluster generally exists in flanking regions of the mevalonate (MV) pathway gene cluster in actinomycetes. Interestingly, Streptomyces sp. strain KO-3988 was the first example of a microorganism equipped with two distinct mevalonate pathway gene clusters. We were able to localize a 25-kb DNA region that harbored FQ A biosynthetic genes (fur genes) in both the upstream and downstream regions of one of the MV pathway gene clusters (MV2) by using heterologous expression in Streptomyces lividans TK23. This was the first example of a gene cluster responsible for the biosynthesis of a polyketide-isoprenoid hybrid compound. We have also confirmed that four genes responsible for viguiepinol [3-hydroxypimara-9(11),15-diene] biosynthesis exist in the upstream region of the other MV pathway gene cluster (MV1), which had previously been cloned from strain KO-3988. This was the first example of prokaryotic enzymes with these biosynthetic functions. By phylogenetic analysis, these two MV pathway clusters were identified as probably being independently distributed in strain KO-3988 (orthologs), rather than one cluster being generated by the duplication of the other cluster (paralogs).

Amino Acid Sequence↗

PubMed2005

Gastrointestinal stromal tumor in a child and review of the literature.

Gastrointestinal stromal tumors (GIST) are c-KIT positive neoplasm that occur predominantly in adults. A 13-year-old boy who presented with massive gastrointestinal hemorrhage was subsequently diagnosed with GIST of the stomach. The tumor originated from the lesser curvature with a narrow base and no infiltration into surrounding organs. Two metastatic lesions in the liver were also found. Total excision of the gastric lesion was performed followed by adjuvant imatinib mesylate chemotherapy. He has had no signs of recurrence during 8 months of follow-up. GIST in children are rare and their behavior is notoriously difficult to predict. We report our experience and review the literature.

Adolescent↗

PubMed2005

Dynamic MR imaging for diagnosis of lesions adjacent to pituitary gland.

In this study, we evaluated the usefulness of dynamic studies for the preoperative diagnosis of tumor lesions adjacent to the pituitary gland. We examined 13 tumors. We obtained pre- and post-contrast thin slice T1-weighted images of the sellar regions. FSE sequences were used for dynamic study. The capability to distinguish the tumor from the pituitary gland and additional information obtained from the dynamic study were evaluated. Two meningiomas were identified more clearly on the dynamic than on the delayed study. In two cavernous hemangiomas, the peripheral nodular stains gradually increased during the dynamic study. For the preoperative evaluation of lesions adjacent to the pituitary gland, the dynamic study can often identify the lesions more clearly and may provide additional information.

Adult↗

PubMed2005

CT arteriography for orbital tumors: diagnostic and surgical value.

The aim of this study is to investigate the efficacy of dynamic computed tomography (CT) during selective angiography (CT-arteriography) of orbital tumors in the evaluation of intratumoral vascular anatomy, feeding artery territory, and histological diagnosis. Among 35 consecutive cases with various orbital lesions, those cases showing tumor staining or pooling of the contrast medium on digital subtraction angiography (DSA) were evaluated by CT-arteriography (n = 14). The information obtained by CT-arteriography was compared with that provided by enhanced MRI (n = 31) and dynamic MRI (n = 21), in which the contrast medium was injected intravenously. In addition to the visualization of fine vascular anatomy, CT-arteriography emphasized areas of nodular enhancement and non-enhancing cystic/necrotic components as well as the intratumoral feeding arteries. Patterns of CT-arteriography were categorized into three subgroups: homogeneous enhancement (benign lymphoid lesion), partial enhancement (schwannomas and carcinomas), and patchy multinodular enhancement (specific for cavernous angiomas). In addition, CT-arteriography with selective arterial catheterization clearly delineated the feeding artery territories. CT-arteriography, with a minimal dose of contrast medium, can offer significant advantages over intravenously injected dynamic neuroimaging, and provides additional valuable preoperative information about the orbital tumor under investigation.

Adult↗

PubMed2005

Psychosocial liaison-consultation for the children who have undergone repair of imperforate anus and Hirschsprung disease.

OBJECTIVE: The aim of this study was to investigate the psychological status of Japanese children with congenital anorectal malformation and their mothers to develop appropriate psychiatric interventions. METHOD: The subjects comprised 50 children with congenital anorectal malformation aged 0 to 16 years and their mothers. The psychology of children aged 7 to 16 years was investigated by Kovacs' Children's Depression Inventory (CDI). The psychology of their mothers was assessed by Spielberger's State-Trait Anxiety Index (STAI) and Zung's Self-rating Depression Scale (SDS). RESULTS: Depression was more marked in the children aged 12 to 16 years than in those aged 7 to 11 years according to the CDI. The mothers of preschool children showed higher levels of anxiety and depression than those of school-aged children, according to the STAI and SDS. Significant correlations between the CDI score of the children and the STAI or SDS score of the mothers were observed only among children aged 7 to 11 years. CONCLUSIONS: The frequency of depression and anxiety among children with congenital anorectal malformation and that among their mothers was associated with the age of the child. Long-term postoperative psychosocial support for the children and their mothers may be required, taking into account the age of the child.

Adolescent↗

PubMed2005

Thoracoscopic removal of neurogenic mediastinal tumors in children.

PURPOSE: The aim of this study was to evaluate the feasibility and advantages of thoracoscopic removal of neurogenic mediastinal tumors (NMTs) in children. METHODS: From January 1998 to December 2001, 6 patients, ages 1.1 to 6.8 years (mean, 3.5 years), underwent thoracoscopic removal of NMT. A retrospective study was done to assess the type of anesthesia, conversions to standard thoracotomy, operative time, complications, and the current status of each patient. RESULTS: General anesthesia using a Fogarty catheter as an ipsilateral bronchial blocker was utilized. Four 5-mm ports were placed in all patients. All NMTs were successfully removed without a need to convert to standard thoracotomy. The tumor was captured in an extraction bag, fragmented, and then removed through the trocar site, which had been enlarged up to 2.0-2.5 cm in each case. Pathologic diagnosis was neuroblastoma in 1 patient, ganglioneuroblastoma in 2, and ganglioneuroma in 3 patients. The mean operative time was 230 minutes. There was no need for transfusion and no serious complication related to this approach. All patients are alive at the time of writing, without any evidence of tumor recurrence. CONCLUSION: All tumors were successfully removed. Thoracoscopic surgery is a feasible, safe, and effective technique in the treatment for children with NMT.

Child↗

PubMed2005

Social adaptation of children with congenital fecal dysfunction: from the viewpoint of the mother-child relationship.

Excretory dysfunction associated with congenital anal anomalies (a generic term that includes anal atresia and Hirschsprung's disease) is presumed to greatly affect the psychology of the affected children. In this study, we conducted a survey on the psychological status of children with excretory dysfunction, and investigated the relationship between the affected children and their families in addition to their social life. Four children with fecal dysfunction due to a congenital anal anomaly and their mothers were interviewed. The results of psychological tests in the children and mothers along with our findings in the interviews with the children and mothers, were included in the data analysis. We found that regardless of the degree of excretory dysfunction, the child's state of mind was influenced by whether the mother exhibited warmth or criticism towards her child and whether there was a support system for the mother and child. We suggest that psychiatric consultation is necessary for these children.

Anal Canal↗

PubMed2005

Concentrations of copper and zinc in liver and serum samples in biliary atresia patients at different stages of traditional surgeries.

Many patients with biliary atresia (BA) have impaired metabolism of copper (Cu) and zinc (Zn) because of the obstruction of bile ducts. An excessive Cu accumulation is cytotoxic and results in fibrosis in hepatic tissues. Since Zn works antagonistically to Cu, lower Zn concentrations may deteriorate liver damage. In the 1980's, we performed a series of surgeries on BA patients for the construction and alteration of the bile flow route, which is the major excretion route for Cu. We obtained liver and serum samples at each surgery, and measured Cu and Zn concentrations by inductively coupled plasma atomic emission spectrometry. Hepatic Cu concentration decreased with the improvement of cholestasis after the establishment of bile excretion. Conversely, when cholestasis persisted or recurred, increases in hepatic and serum Cu concentrations were noted. Hepatic Zn concentration was lower than previously reported normal values. High hepatic and serum Cu concentrations due to persistent or recurrent cholestasis and low hepatic Zn concentration may deteriorate hepatic fibrosis and liver cirrhosis.

Biliary Atresia↗

PubMed2005

Correlation of gamma-catenin expression with good prognosis in medulloblastomas.

OBJECT: Medulloblastoma is a malignant cerebellar tumor of childhood and is difficult to cure due to frequent cerebrospinal fluid dissemination. Amplification of the c-myc gene (4%) and messenger (mRNA) overexpression (50%) are known to be adverse prognostic indicators. Because mRNA overexpression cannot be explained by gene amplification alone, mechanisms other than gene amplification are postulated. Molecules on the Wnt signal pathway in primary tumors were examined. METHODS: Immunohistochemical and cytogenetic examinations of beta- and gamma-catenin, c-myc, N-myc, and cyclin D1 in 24 primary medulloblastomas were conducted, and their clinical relevance was evaluated. Cytoplasmic/membranous staining of beta- and gamma-catenin was detected in 19 (79%) and nine (37%) cases, respectively, and nuclear expression of cyclin D1 and c-myc was detected in six (25%) and 21 (83%) cases, respectively. The expression levels of gamma-catenin in Western blot analysis and immunohistochemistry were similar. By differential polymerase chain reaction, c-myc and N-myc were amplified separately in two large cell/anaplastic medulloblastomas. No cyclin D1 amplification, or beta- or gamma-catenin mutations were found. Kaplan-Meier analysis revealed no dissemination at diagnosis (Chang Grade M0) and gamma-catenin expression was correlated with good prognosis (p = 0.0002 and 0.003, respectively). Expression of gamma-catenin was also significant in the M0 group (p = 0.022). Expression of cyclin D1 showed a trend toward adverse outcome (p = 0.057) and all patients in whom cyclin D1 expression was found died of disease. CONCLUSIONS: Expression of gamma-catenin is of great prognostic value and its immunohistochemistry may be useful for further stratification of treatment. Cyclin D expression may have the potential to be an adverse prognostic indicator.

Adolescent↗

PubMed2004

Frequent gene amplification and overexpression of decoy receptor 3 in glioblastoma.

The decoy receptor 3 (DcR3) gene is amplified at high frequency in human lung, colon, and liver cancers. DcR3 has been demonstrated to produce a secreted member of the tumor necrosis factor receptor superfamily that negatively regulates Fas-mediated apoptosis. In this study we examined DcR3 gene amplification, DcR3 mRNA expression, and DcR3 protein expression in 46 human astrocytic brain tumors by quantitative genomic PCR, quantitative reverse transcription-PCR, and immunohistochemistry, respectively. The DcR3 gene amplification was detected in none of 6 (0%) low-grade astrocytomas, 1 of 16 (6%) anaplastic astrocytomas, and 6 of 24 ( 25%) glioblastomas. Six of 7 (86%) cases with gene amplification exhibited both mRNA overexpression and/or protein overexpression, suggesting that DcR3 mRNA and protein were expressed more abundantly in the cases with gene amplification. We thus concluded that high DcR3 mRNA expression and protein expression may be positively related to the gene amplification in astrocytic brain tumors, especially glioblastomas. Further, we speculated that the DcR3 gene amplification with overexpression may be responsible for malignant features in glioblastomas.

Adolescent↗

PubMed2004

Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.

Hepatoblastoma is one of the most common malignant liver tumors in young children. Recent evidences have suggested that the abnormalities in Wnt signaling pathway, as seen in frequent mutation of the beta-catenin gene, may play a role in the genesis of hepatoblastoma. However, the precise mechanism to cause the tumor has been elusive. To identify novel hepatoblastoma-related genes for unveiling the molecular mechanism of the tumorigenesis, a large-scale cloning of cDNAs and differential screening of their expression between hepatoblastomas and the corresponding normal livers were performed. We constructed four full-length-enriched cDNA libraries using an oligo-capping method from the primary tissues which included two hepatoblastomas with high levels of alpha-fetoprotein (AFP), a hepatoblastoma without production of AFP, and a normal liver tissue corresponded to the tumor. Among the 10,431 cDNAs randomly picked up and successfully sequenced, 847 (8.1%) were the genes with unknown function. Of interest, the expression profile among the two subsets of hepatoblastoma and a normal liver was extremely different. A semiquantitative RT-PCR analysis showed that 86 out of 1188 genes tested were differentially expressed between hepatoblastomas and the corresponding normal livers, but that only 11 of those were expressed at high levels in the tumors. Notably, PLK1 oncogene was expressed at very high levels in hepatoblastomas as compared to the normal infant's livers. Quantitative real-time RT-PCR analysis for the PLK1 mRNA levels in 74 primary hepatoblastomas and 29 corresponding nontumorous livers indicated that the patients with hepatoblastoma with high expression of PLK1 represented significantly poorer outcome than those with its low expression (5-year survival rate: 55.9 vs 87.0%, respectively, p=0.042), suggesting that the level of PLK1 expression is a novel marker to predict the prognosis of hepatoblastoma. Thus, the differentially expressed genes we have identified may become a useful tool to develop new diagnostic as well as therapeutic strategies of hepatoblastoma.

Cell Cycle Proteins↗

PubMed2004

Biliary atresia with associated complicated anorectal and urogenital malformations.

We report on a girl with biliary atresia (BA) who also suffered with anorectal agenesis without fistula and complicated urogenital malformation. The outcome of patients with these severe anomalies is poor, but she has survived without liver and/or renal transplantation for more than 3 years. A careful treatment plan for each anomaly in addition to prevention of cholangitis and urinary tract infection is indispensable for managing these complicated anomalies.

Abnormalities, Multiple↗