Search PubMed⌕ Search

Biomedical subjects

S Suita

Publications and source records attributed to S Suita.

At least 91 records · Page 5Linked to original sources

A microsatellite instability analysis in neuroblastoma based on a high resolution fluorescent microsatellite analysis.

It has recently been reported that mismatch repair enzymes, which are one type of DNA repair enzymes, are the causative genes for a major group of hereditary non-polyposis colon cancers (HNPCC). Abnormalities in the mismatch repair system can be monitored by observing instability at the microsatellite loci (MSI) in cancer cells. MSI has been reported not only in tumors associated with hereditary non-polyposis colorectal cancer but also in sporadic forms of various tumors. No correlation between pediatric malignant tumors and the mismatch repair system has yet been reported. In the present study, we examined the frequency of MSI in 21 neuroblastomas, which are the most common solid tumors in childhood, using a high resolution fluorescent microsatellite analysis. MSI on five microsatellite loci was detected in none of the 21 samples. Other mechanisms independent of mismatch repair deficiency may thus play a role in both tumorigenesis and the development of neuroblastoma.

Child↗

Stratification of treatment of stage 4 neuroblastoma patients based on N-myc amplification status. Study Group of Japan for Treatment of Advanced Neuroblastoma, Tokyo, Japan.

BACKGROUND: It has been shown that children aged more than 12 months with stage 3 and 4 neuroblastoma with N-myc amplification do worse than those without amplification. Development of an innovative chemotherapeutic protocol for patients in such an extremely poor-risk group was the purpose of this study. PROCEDURE: Since March 1991 a new protocol for the treatment of advanced neuroblastoma was started. When N-myc was amplified more than 10-fold, patients received regimen A3, in which cyclophosphamide 1,200 mg/m2 was given on days 1 and 2; hence the dose of cytotoxic drugs was doubled. Patients with fewer than 10 copies of N-myc received regimen new A1, which is very similar to regimen A1 that had been used until March 1991 for all patients with advanced neuroblastoma with/without N-myc amplification. The efficacy of regimen A3 was evaluated. RESULTS: The relapse-free survival rate at 1 and 2 years for stage 4 patients older than 12 months of age with N-myc amplification of more than 10-fold was 43% and 29%, respectively, with regimen A1 and that for the same subgroup of patients treated with regimen A3 since March 1991 was 79% and 49%, respectively; the difference is statistically significant. On the other hand, there were no differences in the relapse-free survival rate at 1 year and 2 years for stage 4 patients with fewer than 10 copies of N-myc between those treated with regimen A1 and those treated with new A1 since March 1991. CONCLUSIONS: Stratification based on N-myc amplification into new A1 and A3 treatment protocols is of significant clinical importance. Regimen A3 was well tolerated and showed an improvement in clinical results in stage 4 patients with N-myc amplified more than 10-fold.

Antineoplastic Combined Chemotherapy Protocols↗

Expression of clara cell 10-kDa protein (CC10) in congenital diaphragmatic hernia.

Clara cell 10 kDa protein (CC10) has been thought to be fairly specific to Clara cells and a major secretory protein that is both synthesized and released from Clara cells. In the present study, morphometric analyses of the immunohistochemical expression of CC10 were carried out on the bronchioles of human neonates with congenital diaphragmatic hernia (CDH) and then compared with morphometric analyses from a gestationally and postnatally age-matched control group in order to clarify the immaturity of Clara cells in CDH lungs. No difference was found in CC10 expression between the affected side and the unaffected side of the lungs in the CDH group. However, compared with the lungs of the control group, the CDH group showed a significant decrease in CC10 expression, namely, the ratio of CC10-positive cells per bronchiole, per unit perimeter of bronchiole, and per unit bronchiolar surface area. These results suggest that in the lungs of CDH cases, a possible delay in either functional maturation or the development of CC10 synthesis by the bronchioles may exist, and this retardation of functional maturation of the airway is also considered to play a role in the postnatal respiratory insufficiency observed in CDH patients.

Bronchi↗

Monitoring of acute allograft rejection by cytological, immunocytochemical, and immunohistochemical studies following rat small-bowel transplantation.

We investigated the role of graft luminal fluid cytology for immunological monitoring of rat small-bowel allograft recipients. Allogeneic transplantation from WKAM (RT1u) to Lewis recipients and syngeneic transplantation using Lewis (RT11) rats were carried out. Twenty centimeters of the proximal jejunum was transplanted as a Thiry-Vella loop. The luminal fluid on days 0, 3, and 6 was examined cytologically using Papanicolaou, periodic acid-Schiff, and Giemsa staining, and immunocytochemically with monoclonal antibodies for macrophages (ED1 and ED2). Full thickness biopsies of graft tissue were evaluated by both immunofluorescence (ED1 and ED2) and by standard histological methods. The cytological examination on day 6 revealed an increase in the number of enterocytes, lymphocytes, and neutrophils, the presence of bacteria, and the depletion of goblet cells in the allografts. Histologically, significant morphological changes of acute rejection were first seen on day 6. Immunofluorescence predicted the acute rejection of the allografts earlier than a histological examination by showing an increase in the number of ED1- and Ed2-positive cells on day 3. Graft luminal fluid cytology and immunofluorescence analysis of ED1 and ED2 cells could thus be used to recognize early acute allograft rejection following small-bowel transplantation.

Animals↗

The role of cellular motility in the invasion of human neuroblastoma cells with or without N-myc amplification and expression.

BACKGROUND/PURPOSE: Patients who have neuroblastomas with N-myc amplification that are extremely invasive and result in distant metastases tend to have a very poor prognosis. The authors reported previously that N-mycamplification and expression might be closely related to the invasiveness of human neuroblastoma cells. However, the role of cellular motility has not yet been clarified in the invasion of neuroblastoma cells. The aim of this study was, therefore, to elucidate the role of cellular motility in the invasion of neuroblastoma cells. METHODS: Six human neuroblastoma cell lines were used for an invasion assay in vitro using polycarbonate filters coated with basement membrane Matrigel. The amplification and expression of N-myc oncogene was examined by Southern and Northern blotting, respectively. The cellular motility was quantified by computerized image analysis on the morphology of cultured cells. RESULTS: IMR-32, GOTO, and DZ, all of which had N-myc amplification, showed a high degree of invasiveness and a high cellular motility, whereas NB-69 and SK-N-SH without N-myc amplification showed an extremely low degree of invasiveness and cellular motility. ST without N-myc amplification, which was established from an aggressive tumor, showed an exceptionally high degree of motility and invasiveness. A transcriptional reduction of the N-myc gene by retinoic acid (RA) decreased the motility, which thus resulted in a marked decline of invasiveness in IMR-32 and GOTO. CONCLUSION: The cellular motility correlated with the invasive capacity of human neuroblastoma cells, which thus indicated that cellular motility may play an important role in invasion.

Cell Movement↗

Mass screening for neuroblastoma at 6 months of age: difficult to justify.

BACKGROUND/PURPOSE: A statistical analysis of the mass screening for neuroblastoma in Japan based on a population study rarely has been reported. This study aims to evaluate retrospectively the effectiveness of mass screening at 6 months of age using the available population data. METHODS: The data on the neuroblastoma cases registered by the Committee for Pediatric Solid Malignant Tumors in the Kyushu area were analyzed based on both screened and unscreened populations in the Kyushu area. RESULTS: From 1988 to 1992, the cumulative incidence of neuroblastoma in children less than 5 years of age was 82 in 484,599 for screened children, and 11 in 92,966 for unscreened children, respectively. Fourteen of the 82 screened patients had negative findings at 6 months of age (MS-negative cases). No significant difference was observed in the cumulative mortality rates from neuroblastoma in children younger than 5 years of age between the screened children and the unscreened children. Six of seven patients who died among the screened children were MS-negative cases with stage III or IV disease. In addition, no significant difference was found in the cumulative mortality rates from the neuroblastoma cases in patients less than 5 years of age between the children screened from 1988 to 1992 (7 of 484,599) and all children from 1980 to 1984 (14 of 668,084). CONCLUSIONS: These findings suggests that the majority of the patients detected by mass screening had a favorable prognosis, and, mass screening in Japan for children less than 6 months of age was not observed to reduce the incidence and mortality from neuroblastoma. Therefore, mass screening at 6 months of age was not found to improve substantially the prognosis of patients with unfavorable neuroblastoma identified over 1 year of age, which is the primary purpose of such mass screening for neuroblastoma.

Evaluation Studies as Topic↗

Non-protein energy overloading induces bacterial translocation during total parenteral nutrition in newborn rabbits.

The effect of energy intake provided by total parenteral nutrition (TPN) on the incidence of bacterial translocation and the relationship between TPN-induced cholestasis and bacterial translocation were investigated in newborn animals. Forty-six Japanese white newborn rabbits were divided into three groups: TPN-H group (high energy TPN; 280 kcal.kg-1.d-1), TPN-L group (low energy TPN; 180 kcal.kg-1.d-1), and a control group (breast fed). On day 8, they were all killed for investigation of the presence of bacterial translocation, for blood chemistry analysis, and for histological examination of the ileum. The incidence of translocation to any of mesenteric lymph nodes and liver and spleen was significantly higher in the TPN-H group (67%) than in both the TPN-L group (13%) and the control group (10%) (P < 0.01). No difference was seen in ileum morphology between the two TPN groups. Although the mean bilirubin level of the TPN-H group tended to be higher than the TPN-L group, whether or not bacterial translocation occurred was not found to be closely related to the degree of TPN-associated cholestasis. In conclusion, parenteral nonprotein energy overloadng increased the incidence of bacterial translocation in the newborn rabbit. However, bacterial translocation did not appear to be associated with the development of TPN-associated cholestasis.

Animals↗

Longterm outcomes and quality of life after Z-shaped anastomosis for Hirschsprung's disease.

BACKGROUND: Z-shaped anastomosis is one of the modifications of Duhamel's procedure that was designed to eliminate the blind rectal pouch and to achieve complete resection of the colorectal septum. It has been the most widely performed operation in Japan for many years. The longterm postoperative function of evacuation and quality of life of the patients are considered important to evaluate this procedure. METHODS: At Kyushu University Hospital, from 1963 to 1997, 127 patients with Hirschsprung's disease underwent Z-shaped anastomosis. As a result, 122 out of 127 patients (96%) survived. The present status and symptoms, and anorectal functions, including a manometric study and barium enema, were evaluated during the clinical followup. RESULTS: A total of 99 of the 122 surviving patients (81%) were available for this study, and the mean postoperative period was 16 years. Evacuation scores in all patients were as follows; excellent, 62.2%; good, 28.6%; fair, 8.2%; and poor, 1.0%. The percentage of the patients who showed severe symptoms was 4.1% for diarrhea, 3.1% for constipation, 5.1% for incontinence, and 7.1% for soiling. The evacuation score improved chronologically and tended to reach a plateau at 10 to 15 years after operation, at which time 73% of the patients showed excellent outcomes and 95% were satisfactory (good or excellent). The appearance of a sense of defecation and an increase in the pressure difference between the anal canal and the rectum substantially contributed to the improvement in the defecation score. The appearance of the rectosphincteric reflex, including the atypical one, was seen in 40.5% of patients, but the appearance of a reflex did not seem to be related to the clinical status of defecation. Twenty-two of 30 patients older than 20 years were married, and 8 patients had children. CONCLUSIONS: The evacuation scores of in-patients undergoing Z-shaped anastomosis improved with age and were satisfactory (good or excellent) in most patients at least 10 years after operation. Most of the patients adapted to a normal social life.

Adolescent↗

Fertility and histological studies in a unilateral cryptorchid rat model during early and late adulthood.

OBJECTIVE: To investigate the effect of age on fertility and testicular development in rats with untreated unilateral undescended testes. MATERIALS AND METHODS: Newborn male Wistar King-A rats were divided into two groups. In group 1, a mechanical model of unilateral undescended testis was created by performing extra-abdominal fixation of the gubernaculum in the neonatal period, and in group 2, sham-operated rats were used as controls. At 90 days old (early adulthood), the fertility of both groups was assessed by mating the rats with mature virgin females for 2 weeks. Thereafter, some of the rats were killed and their testes examined histologically, while the remaining rats were allowed to develop further. At the age of 180 days (late adulthood), fertility was re-assessed in the same way. All the rats were then killed and their testes removed for histological examination. RESULTS: There was no significant difference in pregnancy rate of females mated with males from either group in early adulthood. However, in late adulthood there was a significant reduction in pregnancy rate in females coupled with cryptorchid rats compared with that of females coupled with control rats. There was a significant degeneration of the unilateral cryptorchid testes compared with control testes in both early and late adulthood. In contrast, there were no significant changes in histological development between the contralateral scrotal testes and the controls in early adulthood, although they were significantly different from the controls in late adulthood. CONCLUSION: These results suggest that fertility is affected by ageing in untreated unilateral cryptorchidism; this may be induced by extensive damage not only in the undescended testes, but also in the contralateral scrotal testis, in this mechanically induced model of unilateral cryptorchidism.

Aging↗

Fertility and histological studies of the contralateral testes in two different intra- and extra-abdominal rat models of unilateral cryptorchidism.

OBJECTIVE: To investigate the effect of location of the testis on both testicular development and fertility in unilateral cryptorchidism. MATERIAL AND METHODS: Forty-nine Wistar King A newborn male rats were divided into three groups. In group 1 (15 rats) intra-abdominal unilateral cryptorchidism were created by the intra-abdominal fixation of the testis in the neonatal period. In group 2 (16 rats) extra-abdominal unilateral cryptorchidism was created by extra-abdominal fixation of the gubernaculum in the neonatal period. In group 3, 18 rats underwent a sham operation as controls. At 90 days of age, fertility was then assessed in each rat by housing it with two mature virgin females for 2 weeks. Thereafter, at 115-120 days of age, the rats were killed and their testes removed for histological examination. RESULTS: There was no significant difference in the pregnancy rate between females coupled with rats from any group, but the mean number of offspring was significantly lower in females coupled with rats in group 1 than in group 2. Furthermore, histological examination of both the cryptorchid and contralateral scrotal testes showed more severe changes in the intra-abdominal than the extra-abdominal testes. CONCLUSION: These results suggest that intra-abdominal cryptorchid testes are significantly more impaired than extra-abdominal cryptorchid testes, and that such impairment might be caused by exposure of the testis to a higher temperature. The more severely impaired undescended testes may thus induce the degeneration of the contralateral scrotal testis and thereby cause subfertility in the intra-abdominal unilateral cryptorchid rat model.

Animals↗

Long-term results and clinical problems after portoenterostomy in patients with biliary atresia.

From January 1962 through December 1986, 71 cases of biliary atresia were operated on. Nine of these patients underwent only an exploratory laparotomy. A hepatic portoenterostomy (Kasai's operation) was performed on 62 infants with biliary atresia. Of these 62 children, 18 survived more than 10 years. However, 4 of the 18 died shortly thereafter because of persistent or recurrent jaundice and hepatic failure. Fourteen patients, however, are still alive more than ten years after portoenterostomy, today the actual 10-year survival rate is thus 22.5%. Six of them have no severe complications and their serum total bilirubin is less than 1.0 mg/dl. However, 8 patients, whose serum total bilirubin is more than 1.0 mg/dl, demonstrated numerous clinical problems such as esophageal varices, hypersplenism and recurrent jaundice after cholangitis. One of the patients in the latter group eventually underwent a liver transplantation because of the recurrent jaundice and hepatic insufficiency. In the treatment of biliary atresia, a close and careful follow-up is therefore essential especially for patients whose serum total bilirubin is more than 1.0 mg/dl.

Biliary Atresia↗

Membrane properties and the neuro-effector transmission of smooth muscle cells in the canine internal anal sphincter.

The most distal part of the circular muscle layer functions as the internal anal sphincter, which constitutes a high pressure zone at rest, but maintains a relaxed state during defecation. To elucidate such sphincter mechanisms of the smooth muscle cells, the circular muscle layer in the canine anal canal was examined within 2 cm from the anal verge. Both the mechanical and intracellular electrical activities were recorded simultaneously. The examined region could be divided into three different regions according to the pattern of spontaneous activity and innervation and consisted of an upper region (20-15 mm from the anal verge), a transitional region (15-5 mm from the anal verge) and a lower region (within 5 mm from the anal verge), respectively. The spontaneous membrane activity was characterized by ongoing slow potential changes and each potential change was associated with a phasic contraction in the three regions. The mean frequencies of spontaneous electrical activity were 6.8, 15.9, and 24.1 c/min in the upper, transitional and lower regions, respectively. In the transitional and lower region, muscle tone generation was observed. Transmural field stimulation (0.4 msec in pulse duration) evoked membrane depolarization and contractions in the lower region. The application of an alfa adrenergic blocking agent completely suppressed the generation of excitatory responses, leaving a long lasting hyperpolarization associated with relaxation. In the transitional and upper region, stimulation consistently evoked membrane hyperpolarization with relaxation. The characteristics of this hyperpolarization response varied among the three regions. The total duration of hyperpolarization increased distally, while the time to peak hyperpolarization became decreases in a reverse direction. These regional differences in the characteristics of spontaneous membrane activity and innervation indicate that the transitional and lower region might therefore function as the internal anal sphincter.

Anal Canal↗

Value of MR cholangiopancreatography in evaluating choledochal cysts.

OBJECTIVE: The aim of this retrospective study was to clarify whether MR cholangiopancreatography (MRCP) is a suitable replacement for ERCP in evaluation of the choledochal cyst. MATERIALS AND METHODS: Sixteen patients (six adult and 10 pediatric) with choledochal cysts underwent MRCP using a half-Fourier acquisition single-shot turbo spin-echo sequence. Extent of the cyst, defects within the biliary tree, and presence or absence of the anomalous junction of the pancreaticobiliary duct were evaluated. Findings were compared with those of ERCP. RESULTS: MRCP better defined the proximal biliary tree than did ERCP in two patients. Defects within the biliary tree were diagnosed correctly on MRCP in eight patients; however, two defects within the distal common bile duct were missed in pediatric patients. The presence of the anomalous junction of the pancreaticobiliary duct was revealed accurately by MRCP in all adult patients but was revealed accurately in only four of the 10 pediatric patients. CONCLUSION: MRCP appears to offer diagnostic information that is equivalent to that of ERCP for assessment of choledochal cysts in adults. In pediatric patients, MRCP should not replace ERCP; however, MRCP can play an important role as a noninvasive examination and should be considered a first-choice imaging technique for evaluation of choledochal cysts.

Adult↗

[TNM classification--pediatric tumors].

The clinical and postsurgical TNM classifications (cTNM and pTNM) for neuroblastoma (NB), nephroblastoma (WT) and soft tissue sarcomas were presented in 1982 by the TNM Committee in UICC in collaboration with SIOP. The Japanese TNM Committee proposed new pTNM systems (J-pTNM) for NB and WT, and new cTNM and pTNM system for primary liver carcinoma in infants and children (HT). These pTNMs were based on the staging systems developed by the Malignant Tumor Committee of the Japanese Society of Pediatric Surgeons. The proposal of subdivision of M category in NB was presented for testing the new telescopic ramifications of TNM. The TNM for HT was added as a new classification recommended for testing. The effectiveness of these TNM systems was assessed using NB, WT and hepatoblastoma (HB) cases which were registered in collaborating institutes. The analyses suggested that pTNM, especially the J-pTNM system in NB, WT and HT were effective for the assessment of prognoses, although cTNM systems were not enough to assess the extent of the disease.

Child↗

[Recent advances in the nutritional management of pediatric surgical patients].

The prognosis of pediatric surgical patients is significantly improved by perioperative nutritional support. However, the morbidity and mortality rates from intestinal failure, including short gut syndrome and allied disorders of Hirschsprung's disease, remain high. Recent advance in nutrition support focus on the management of intestinal failure. A central venous catheter is commonly used for long-term total parenteral nutrition (TPN) in intestinal failure, although the incidence of catheter-related complications is still high. A nutrition support team approach might reduce such complications, with the exception of deep vein thrombosis, which is another serious problem in intestinal failure after long-term TPN on which more research is needed. A other serious complication in long-term TPN is liver dysfunction. It is postulated that bacterial translocation plays an important role in TPN-associated liver damage, although so far without evidence. Both cyclic TPN and enteral feeding are known to be effective in preventing liver damage. Since we are now familiar with methods of nutritional support little attention is paid to complications. Therefore nutritional management should be reevaluated from this standpoint.

Child↗