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Biomedical subjects

Sachiyo Suita

Publications and source records attributed to Sachiyo Suita.

At least 19 recordsLinked to original sources

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↗

Epstein-Barr virus-associated bronchial leiomyoma in a boy with cellular immunodeficiency.

Bronchial leiomyoma is a rare disease in children. Recently, the association of leiomyoma and HIV infection was reported. We describe a boy with a cellular immunodeficiency, who had endobronchial leiomyoma. The tumor cells were positive for Epstein-Barr virus-encoded RNA-1 (EBER-1) and Epstein-Barr virus-determined nuclear antigen-2, suggesting a role of Epstein-Barr virus in the pathogenesis of leiomyoma.

Bronchial Neoplasms↗

Biological diagnosis for neuroblastoma using the combination of highly sensitive analysis of prognostic factors.

BACKGROUND/PURPOSE: To select the optimal treatment according to the degree of malignancy of neuroblastoma, it is essential to accurately and rapidly identify any genetic abnormalities associated with the prognosis. This study aims to assess the correlation between the combination of prognostic factors and the biologic findings of neuroblastoma using a highly sensitive analysis of prognostic factors. METHODS: In 44 neuroblastoma primary samples, we determined the gene dosages of MYCN and Survivin (as the target of 17q gain) and the expression levels of MYCN, Survivin, and BIN1 using highly sensitive analysis (the quantitative polymerase chain reaction method); furthermore, we assessed the correlation between the combination of their prognostic factors and the biology of neuroblastoma. RESULTS: The gene dosage of MYCN or Survivin was significantly associated with all known prognostic factors. The expression level of MYCN or Survivin was not significantly associated with any prognostic factors, whereas the expression level of BIN1 was significantly associated with 5 of 6 prognostic factors. Regarding the combination of MYCN amplification and 17q gain (the gene dosage of Survivin), and the low expression of BIN1, the rates of advanced stages (stage III or IV) were 100% for the cases with 3 factors, 63% for the cases with 2 factors, 42% for the cases with 1 factor, and 0% for the cases with null factor. Furthermore, the survival rates were 20% for the cases with 3 factors, 50% for the cases with 2 factors, 100% for the cases with 1 factor, and 100% for the cases with null factor. CONCLUSION: The combination of gene dosages of MYCN and Survivin and the expression level of BIN1 using the quantitative polymerase chain reaction method was significantly correlated with the clinical stage and the patients' outcome. This combination of biologic factors may enhance the accuracy to the conventional criteria, but this would have to be shown in a much larger study that is adequately powered to detect such an advantage.

Adaptor Proteins, Signal Transducing↗

Increased expression of c-fos and c-jun in the rat small intestinal epithelium after ischemia-reperfusion injury: a possible correlation with the proliferation or apoptosis of intestinal epithelial cells.

BACKGROUND AND PURPOSE: An increased expression of immediate early genes, such as the c-fos and c-jun, is observed in some organs after ischemia-reperfusion (I/R) injury. These factors have been revealed to potentially induce apoptosis and proliferation of the postischemic cells. The purpose of this study is to analyze the relationship between the expression patterns of such immediate early genes and the cellular responses in the intestinal epithelial cells (IECs) after I/R stress. METHODS: The rat small intestine was reperfused after 30 minutes ischemia. Semiquantitative reverse transcription-polymerase chain reaction was used to quantify c-fos and c-jun messenger RNAs. The proliferation and apoptosis of IECs were detected by immunohistochemistry and the in situ terminal deoxynucleotidyl transferase-mediated dUTP biotin nick-end labeling method, respectively. RESULTS: The messenger RNA levels of the c-fos and c-jun showed characteristic patterns in the IECs after the I/R stress. The proliferation of the cells was initially observed after the I/R stress, followed by apoptosis of the cells. CONCLUSIONS: The sequential expression patterns of these factors are possibly related to the proliferation and apoptosis of the IECs.

Animals↗

Age-specific effect of phthalate ester on testicular development in rats.

PURPOSE: Phthalate esters have been shown to induce testicular damage in both adult and immature rats; however, there have been, so far, few reports describing the age-specific effects of phthalate esters on testicular function. The aim of this study is therefore to investigate the age-specific effects of mono-n-butyl phthalate (MBP) on the testes in both prepubertal and mature adult rats. MATERIALS AND METHODS: Both prepubertal male rats and adult mature male rats were fed special rat chow containing 1% MBP for 10 days. Control prepubertal and adult rats were fed standard commercial rat chow during the same period as the MBP-treated rats. After 10 days of feeding, all rats were killed, and the testes were removed. The weight of the testis was measured, and histological examination of the testis was performed. In addition, the frequency of an apoptotic cell appearance in the seminiferous tubules was determined in both MBP-treated and control groups. RESULTS: In the prepubertal rats, the mean weight of the testes was significantly lower in the MBP-treated rats than in the control rats. A histological examination of the MBP-treated testes showed a decreased seminiferous tubular diameter and an inhibited maturation of germ cells in comparison to those of the control testes. Furthermore, apoptotic cells appeared more frequently in the MBP-treated testes than in the control testes. Although in adult mature rats, no significant difference was observed in either the testicular weight or the histological findings between the MBP-treated and control rats. CONCLUSIONS: The oral administration of MBP to male rats was observed to produce more pronounced testicular damage in prepubertal rats than in adult mature rats. Immature testes may thus be more sensitive to MBP, which induces the germ cell apoptosis in seminiferous tubules and testicular atrophy in prepubertal young rats.

Age Factors↗

A case of an abdominoscrotal hydrocele surgically treated under laparoscopic assistance.

We herein describe a 9-month-old boy who presented with bilateral scrotal hydroceles shortly after birth. The right hydrocele spontaneously resolved during this period, and a nonpalpable testis of the right side was noted. In contrast, the left hydrocele gradually increased in size. Ultrasound and magnetic resonance investigations performed at the age of 7 months could not detect the right testis either in the inguinoscrotal region or the abdominal cavity. These examinations also pointed out a huge hydrocele that extended from the left scrotum to the abdominal cavity. At the age of 9 months, a laparoscopic-assisted operation for both the right undescended testis and the left abdominoscrotal hydrocele (ASH) was performed. During the operation, an atrophic testis secondary to in utero intravaginal torsion was shown on the right inguinal region, and a huge ASH was revealed in the left inguinoscrotal region. The finding of the left ASH was confirmed by a laparoscope inserted through the processus vaginalis of the right side. At first, the processus vaginalis of the left side was highly ligated by the inguinal approach, and then the ASH was opened and its wall was resected. Our findings suggest that both an understanding of the pathogenesis and a corrective operation of ASH can be made via the inguinal approach. In cases associated with cryptochidism owing to an intraabdominal testis or an in utero extravaginal torsion, a laparoscopic-assisted operation may therefore be useful both for making a precise diagnosis and for surgically removing an ASH.

Comorbidity↗

Clinical characteristics and outcome of Wilms tumors with a favorable histology in Japan: a report from the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan.

BACKGROUND/PURPOSE: Since 1996, the standard treatment of Wilms tumors in Japan has been based on the regimen of the Japanese Wilms Tumor Study. However, in Japan, there have been no reports about Wilms tumors that analyzed the clinical features and patient outcome in a large series until now. This study aims to assess the clinical characteristics of patients with Wilms tumor with a favorable histology from a retrospective standpoint in the Kyushu area in Japan and, furthermore, to analyze the historical changes of clinical features and outcome from the 1980s to the 1990s. METHODS: Between 1982 and 1996, 90 cases of Wilms tumors with a favorable histology were registered in the Kyushu area. Regarding the clinical feature and outcome, they were divided into 2 groups (group A, 1982-1989, n = 50; group B, 1990-1996, n = 40). The outcome was analyzed based on the 5-year overall survival rate. RESULTS: The clinical features (age, sex, initial symptom, location, stage) demonstrated no definite differences between group A and group B. Regarding the operation, the rate of an initial complete resection in the early stages was significantly higher in group B than in group A. All stage V cases in group B undewent a bilateral tumor biopsy instead of a radical nephrectomy as the initial operation. The 5-year overall survival rate throughout the whole period was 87.8%, whereas the rates were 84.0% for group A and 90.0% for group B (P = NS), respectively. Of particular note, the outcome of patients with stage I and stage V in group B substantially improved in comparison to that in group A. However, in advanced cases, no significant improvement in the outcome was noted. CONCLUSIONS: This is the first report about the clinical features and outcome for Wilms tumors with a favorable histology in Japan from the 1980s to the 1990s. The present study suggested that in the early-stage cases, an initially complete resection followed by standard postoperative chemotherapy substantially improved the outcome of the patients in group B. In the stage V cases, the performance of renal salvage surgery may have positively contributed to the improvement in the outcome in group B. However, in the advanced stage cases, no definite improvement was noted. In the future, an improved efficacy of the treatments for Wilms tumors based on the standard protocol established by the Japanese Wilms Tumor Study in 1996 is expected in Japan.

Child, Preschool↗

Experimental study concerning safety dosage of OK-432 for intrauterine treatment.

OBJECTIVE: Clinical intrauterine treatment for fetal cystic hygroma has so far been performed in a few patients; however, it is still difficult to evaluate the results. The aim of this study is to establish the safe dosage of OK-432 in the intrauterine treatment of fetal cystic hygroma. METHODS: OK-432 was injected either subcutaneously behind the neck of the fetuses or into the amniotic cavity through the uterine wall of pregnant Japanese white rabbits at 27 days of gestation. Saline was administered to the controls. The dosage and the site of injection were as follows: group 1, OK-432, 0.01 KE (0.25 KE/kg) in 0.2 mL saline per fetus, subcutis; group 2, OK-432, 0.02 KE (0.5 KE/kg) in 0.2 mL saline per fetus, subcutis; group 3, OK-432, 0.04 KE (1 KE/kg) in 0.2 mL saline per fetus, subcutis; group 4, OK-432, 0.01 KE in 0.2 mL saline per fetus, amniotic cavity; group 5, OK-432, 0.04 KE in 0.2 mL saline per fetus, amniotic cavity; group 6, saline, 0.2 mL per fetus, subcutis; group 7, saline, 0.2 mL per fetus, amniotic cavity. All fetuses were delivered at 29 days of gestation. RESULTS: The mother's rectal temperature was mostly in the normal range throughout the experiment. There was no significant difference between any of the seven groups in fetal body weight. The C reactive protein values of all fetuses were negative. The appearance of the skin of all the fetuses was normal. The histopathological findings of the skin in the OK-432 groups showed a moderate infiltration of monocytes and plasma cells. No pathological changes were observed in the heart, lung, liver or kidneys of any of the fetuses. CONCLUSION: Based on this rabbit experiment, we determined that OK-432 may be safely used at a dose of up to 1 KE/1 kg of fetal body weight as an intrauterine treatment for fetal cystic hygroma.

Amnion↗

Oesophageal atresia with a terminal deletion of chromosome 2q37.1.

We herein report the case of a newborn girl with oesophageal atresia associated with cardiac and gastrointestinal anomalies, including patent ductus arteriosus, tracheomalacia, and gastro-oesophageal reflux with hiatus hernia. In addition, she had a terminal deletion of the long arm of chromosome 2, with a breakpoint of 2q37.1. The patient died following a cardiac arrest at 90 days of age. No cause of death was identified at autopsy.

Abnormalities, Multiple↗

Ventromedial hypothalamic nucleus-specific enhancer of Ad4BP/SF-1 gene.

Ad4BP/SF-1 [Ad4 binding protein/steroidogenic factor-1 (designated NR5A1)] is a transcription factor essential for animal reproduction. Based on the phenotypes observed in gene-disrupted mice, Ad4BP/SF-1 is thought to be involved in establishment of the hypothalamic-pituitary-gonadal axis. However, the mechanisms underlying tissue-specific expression of Ad4BP/SF-1 are largely unknown. Here, we investigated the cis-regulatory regions of the mouse Ad4BP/SF-1 gene by transgenic mouse assays, and identified a ventromedial hypothalamic nucleus (VMH)-specific enhancer. The enhancer localized in intron 6 is highly conserved between mouse, human, and chick. The enhancer has the potential to reproduce endogenous gene expression from the fetal ventromedial diencephalon to the adult VMH. The VMH enhancer was characterized by the presence of suppressive and activating elements. Mutation of the former element resulted in ectopic lacZ reporter gene expression in an area dorsal to the intrinsic expression domain and in the ventricular zone, whereas mutations in the latter containing ATTA motifs led to the disappearance of the reporter gene expression, suggesting the involvement of homeobox proteins. Using nuclear extracts prepared from the adult hypothalami, EMSAs identified specific protein binding to the activating elements but not to the suppressive element.

Animals↗

Colonic stricture secondary to hemolytic uremic syndrome caused by Escherichia coli O-157.

Shiga toxin-producing Escherichia coli (E. coli) is known to be one of the main causes of hemolytic uremic syndrome (HUS). Of the secondary complications of HUS, colonic stricture is relatively rare. We herein report on a Japanese girl that demonstrated sigmoid colon stricture secondary to HUS caused by an infection of E. coli O-157. Severe HUS occurred after the E. coli O-157 infection, so hemodialysis was performed due to renal failure. However, 1 month after recovery from HUS, abdominal symptoms occurred. A contrast study in the colon revealed a sigmoid colon stricture. The stricture was operatively resected. Thereafter, her postoperative course was uneventful. We also review the occurrence of this complication secondary to HUS in the literature.

Child, Preschool↗

Extraosseous accumulation of (99m)Tc-HMDP to radiation nephropathy, mimicking recurrent neuroblastoma.

OBJECTIVE: The aim of this study is to clarify the period of extraosseous accumulation of (99m)Tc-hydroxymethylenediphosphonate (HMDP) to radiation nephropathy mimicking recurrent or remnant neuroblastoma in the pararenal region. METHODS: We reviewed five neuroblastoma and one ganglioneuroblastoma patients (2 boys and 4 girls aged 1-9 years) who underwent (99m)Tc-HMDP bone scintigraphies periodically before and after radiation therapy. RESULTS: Increased renal uptake coincident with the radiation port appeared in 5 of 6 patients from 0 to 3 months (mean 1.7 months), and persisted up to 7 months after the completion of radiotherapy. Renal uptake of (99m)Tc-HMDP was gradually decreased, and eventually became accumulation defects in 5 of 6 patients from 6 to 17 months (mean 8.9 months) after radiotherapy. CONCLUSION: When extraosseous accumulation is found after radiation therapy in neuroblastoma patients, radiation nephropathy would be a candidate in the differential diagnosis besides recurrent or remnant tumor.

Bone Neoplasms↗

Effect of liver transplantation on multiple bone fractures in an infant with end-stage biliary atresia: a case report.

Osteodystrophy is frequently found in children with chronic cholestatic liver disease. We herein report an end-stage case of biliary atresia that was associated with multiple bone fractures and severe growth retardation. The patient, an 8-month-old female, underwent a living-related liver transplantation and thereafter showed a dramatic improvement in growth and decrease in bone fractures. A correction of the liver function is therefore considered to be a key factor in treating osteodystrophy that is related to chronic cholestatic liver disease. It is also essential to perform liver transplantation at the most appropriate time to enhance and support the growth of these patients.

Biliary Atresia↗

Effect of a valine-rich diet on a rat model of short bowel syndrome.

It has been recently reported that valine, which was one of the branched chain amino acids, enhanced liver regeneration after a hepatectomy in rats. The aim of this study is to investigate the effect of enteral valine supplementation on the intestinal adaptation of short bowel syndrome using a rat model. Seven-week-old male Lewis rats underwent a 90% small bowel resection. The rats were randomly divided into two groups; Group V (valine-rich diet which contains valine, five times as the normal amount of valine as that found in standard rat chow) and Group S (standard rat chow), according to the diet each group received. The rats were killed and evaluated at the operative day, and postoperative days (POD) 7, 14, 30, and 60, respectively. The parameters of estimation were body weight (BW), a blood amino acids analysis, a urine organic acids analysis and a morphological examination of the residual small intestines. The BW and the intestinal wet weight, jejunal crypt depth and proliferating cell nuclear antigen positive cells in Group V at POD 7 were significantly higher than in Group S, while those in the Group V at POD 30 and 60 were smaller than in Group S. The urine methylmalonic acid (MMA) level in Group V at POD 30 and 60 was much higher than in Group S. The valine-rich diet was thus found to enhance intestinal regeneration after a small bowel resection in the acute phase. However, the long-term valine-rich diet supplementation was found to disturb the intestinal adaptation, which might be caused by the high production of MMA due to the valine-rich diet. This is the first report in which valine was used as a promoter of intestinal adaptation.

Adaptation, Physiological↗

Efficacy of OK-432 local injection for the treatment of a neonatal branchial cleft cyst: a case report.

We herein present a case of a neonatal cervical cyst, which was diagnosed prenatally, and markedly decreased in size and disappeared after a local injection therapy of OK-432. A 0-day-old boy had an abnormal prenatal ultrasonography scan suggestive of rt. cervical cyst, measuring about 25 mm in diameter at 29 weeks' gestation. At birth, an elastic soft mass, measuring about 30 mm in diameter, was found on the right side of his neck. Computed tomography (CT) scans showed a giant cyst, which extended from the upper level of epipharynx to the upper mediastinum, and the contents were air and fluid. At 20 days of age, ultrasonography (US)-guided needle aspiration was performed. The aspirated fluid contained no epithelial cells, but many lymphocytes and neutrophils based on a cytological analysis. After the local injection of OK-432 had been performed four times, the right neck cyst had almost completely disappeared on US scans. During the local injection therapy, we analyzed the other sample of the second aspiration fluid of the neck cyst. Several clusters of epithelial cells, columnar epithelium, squamous cells, and ciliated epithelium were thus cytologically observed. Therefore, a final diagnosis of a branchial cleft cyst was made. The local injection of OK-432 was thus found to be an effective treatment for branchial cleft cysts.

Antineoplastic Agents↗

Hirschsprung's disease in Japan: analysis of 3852 patients based on a nationwide survey in 30 years.

BACKGROUND/PURPOSE: The introduction of laparoscope and transanal endorectal pull-through has caused a revolution in the operative procedures for Hirschsprung's disease. To study the changing profile of Hirschsprung's disease in Japan, the authors carried out a national survey. METHOD: Patient data were collected in 3 phases: group 1, 1628 patients between 1978 and 1982; group 2, 1121 patients between 1988 and 1992; and group 3, 1103 patients between 1998 and 2002, respectively. RESULTS: The incidence was 1:4697, 1:5544, and 1:5343 and the male/female ratio was 3.0:1, 3.4:1, and 3.0:1 in each group, respectively. Patients weighing less than 2500 g at birth increased to 10.4% in group 3, whereas they were 6.5% in group 2 and 5.5% in group 1. The patients with a family history also increased to 6.0% in group 3, in comparison with 2.8% in group 2 and 3.0% in group 1. The incidence of associated anomalies increased over time, 11.1% in group 1, 16.3% in group 2, and 21.2% in group 3. Mutations of genes were found in 4 of the 23 patients examined. The extent of aganglionosis was almost the same in each group. Regarding the definitive operation, the procedures without laparotomy, including transanal endorectal pull-through, increased up to 42.6% in group 3 but 0% in groups 1 and 2. The frequency that a primary operation without stoma was performed also increased. The age at definitive operation decreased in group 3. The incidence of preoperative and postoperative enterocolitis also decreased over time. The mortality was decreased over time, 7.1%, 4.9%, and 3.0% for groups 1, 2, and 3, respectively. CONCLUSIONS: The authors analyzed 3852 Japanese patients over 3 decades. The ratio of patients with a low birth weight, associated anomalies, or a family history was increased in the last 10 years. A primary operation without laparotomy has thus become the procedure of choice for a definitive operation.

Anal Canal↗

Long-term effects of intrauterine exposure to mono-n-butyl phthalate on the reproductive function of postnatal rats.

PURPOSE: Although it is well known that phthalate esters induce testicular dysfunction in both adult and immature rats, there have been few reports on the long-term effect of phthalate esters on the testicular function of male rats exposed to phthalate esters in utero. This study was designed to assess the long-term effects of the mono-n-butyl phthalate (MBP) ester on the testicular function of neonatal and adult rat offspring from pregnant dams exposed to phthalate esters during gestation. METHODS: Pregnant rats were administered MBP [0.5 g/(kg body weight/.d); 4 days] by gavage from the 15th to the 18th gestational day. Rats administered solvent only were used as control subjects. After the rats' puberty, using male pups whose testes descended normally, the authors examined their fertility while also measuring their testicular weights, mean seminiferous tubular diameter, and the developmental grade of the germ cells (Johnsen score) in their testes. Next, in neonatal rats, the authors measured the testicular concentration of the Mullerian inhibiting substance (MIS) protein using enzyme-linked immunoassay and the expression level of the MIS messenger RNA using the quantitative polymerase chain reaction method as a marker of the Sertoli cells' function. Next the concentration of testosterone protein using a radioimmunoassay as a marker of the Leydig cells' function was measured. RESULTS: The pregnancy rate of the female rats coupled with MBP-treated male rats decreased significantly in comparison with that of the female rats coupled with control male rats (P < .01). Both the testicular weight and the Johnsen score in the MBP-treated group were decreased significantly more than those of the control group (P < .05). Neither the concentration of the MIS protein nor the expression level of the MIS messenger RNA in the MBP-treated neonatal testes differed from those of the control testes, whereas the concentration of testosterone protein in the neonate testes decreased significantly in the MBP-treated group in comparison with that of the control group (P < .01). CONCLUSIONS: A prenatal short-time exposure to MBP induces a long-term effect on postnatal rats and impairs reproductive function in male offspring probably by inhibiting the Leydig cells' rather than Sertoli cells' function in the fetal period.

Animals↗

Fatty liver caused by portal vein thrombosis after living donor liver transplantation: a case report.

Portal vein thrombosis (PVT) is a rare complication that occurs after liver transplantation: however, it cannot be ignored as a cause of graft loss and death. We herein report a pediatric case of PVT that caused a fatty change in the graft after living donor liver transplantation. The portal vein was successfully reconstructed using the left great saphenous vein of the same donor. Moreover, the fatty liver recovered after the operation. Our case suggests that the finding of fatty liver is an important marker of PVT and immediate portal reconstruction is performed.

Fatty Liver↗