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Biomedical subjects

H Komuro

Publications and source records attributed to H Komuro.

At least 19 recordsLinked to original sources
PubMed2003

Recent advances in cerebellar granule cell migration.

In the developing brain, postmitotic neurons exhibit dynamic changes in mode, direction, tempo and rate of migration as they traverse different cortical layers. Such changes in cell migration require orchestrated activities of multiple guidance cues and transmembrane signals. In this article, we first describe when, where and how cerebellar granule cells alter their migratory behavior during the entire course of their migration. We then present how internal (inherent) programs regulate the sequential changes in the migratory behavior of granule cells in vitro. Finally, we discuss the roles of external guidance cues and transmembrane signals in controlling granule cell migration.

Animals↗
PubMed2001

Mode and tempo of tangential cell migration in the cerebellar external granular layer.

After their final mitosis, cerebellar granule cells remain in the external granular layer (EGL) for 20-48 hr before initiating their radial migration across the molecular layer (ML), but the significance of this latent period is not well understood. In the present study, we used a confocal microscope to examine morphogenetic changes and behavior of postmitotic granule cells restricted to the EGL in slice preparations of the postnatal mouse cerebellum. We found that, coincident with the extension of two uneven horizontal processes oriented parallel to the longitudinal axis of the folium, postmitotic granule cells start to migrate tangentially in the direction of the larger process. Interestingly, their morphology and the speed of cell movement change systematically with their position within the EGL. The rate of tangential cell movement is fastest (approximately 14.8 micrometer/hr) in the middle of the EGL, when cells have two short horizontal processes. As granule cells elongate their somata and extend longer horizontal processes at the bottom of the EGL, they move at a reduced rate (approximately 12.6 micrometer/hr). At the interface of the EGL and ML where cells migrate tangentially at the slowest rate (approximately 4.1 micrometer/hr), their somata round and then begin to extend couples of the descending processes into the ML. After the stationary period, granule cells abruptly extend a single vertical process and initiate the transition from tangential to radial migration, reshaping their rounded somata into a vertically elongated spindle. These observations suggest that tangential migration of granule cells within the EGL may provide the developmental mechanisms for their appropriate allocation across parasagittal compartments of the expanding cerebellar cortex.

Animals↗
PubMed2001

The osteoprotegerin/receptor activator of nuclear factor kappaB/receptor activator of nuclear factor kappaB ligand system in cartilage.

OBJECTIVE: The receptor activator of nuclear factor kappaB (RANK) is a member of the tumor necrosis factor receptor family. It is activated by the secreted or cell surface-bound RANK ligand (RANKL). Osteoprotegerin (OPG) is a soluble nonsignaling receptor for RANKL and interferes with RANK activation. This receptor-ligand system regulates the differentiation of osteoclasts and dendritic cells. The present study examined human articular cartilage for the expression of these molecules and the role of RANKL in the regulation of chondrocyte function. METHODS: Normal and osteoarthritic (OA) human articular cartilage was used for explant tissue culture or for isolation of chondrocytes and cell culture. Expression of RANK, RANKL, and OPG was analyzed by immunohistochemistry, Western blotting, or reverse transcription-polymerase chain reaction. Recombinant RANKL was added to cartilage or chondrocyte cultures, and gene expression, collagenase and nitric oxide production, and NF-kappaB activation were determined. RESULTS: RANK, RANKL, and OPG messenger RNA (mRNA) were expressed in normal cartilage. By immunohistochemistry, RANK, RANKL, and OPG were detected in the superficial zone of normal cartilage. OA cartilage contained increased levels of OPG mRNA, and expression of the 3 proteins extended into the midzone of OA cartilage. OPG was detected by Western blotting, and was increased in response to interleukin-1beta stimulation. OPG, RANK, and RANKL protein were also detected in cultured chondrocytes. Addition of exogenous RANKL did not activate NF-kappaB, induce expression of genes encoding proinflammatory mediators in chondrocytes, or stimulate the production of collagenase and nitric oxide. CONCLUSION: These results demonstrate the expression of OPG, RANK, and RANKL in cartilage. However, RANKL does not activate human articular chondrocytes.

Carrier Proteins↗
PubMed2001

Pancreatic complications in choledochal cyst and their surgical outcomes.

Follow-up results were analyzed to evaluate the surgical managements of pancreatic complications such as pancreatitis and protein plug formation in patients with choledochal cysts. Sixty-two patients with choledochal cysts treated between 1976 and 1999 were reviewed. Twenty-four were children and 38 were adults. Fifty-four patients showed primary cases. Cyst excision and hepaticoenterostomy were finally performed in 56 patients. Surgical sphincteroplasty or endoscopic sphincterotomy was performed to prevent recurrent protein plugs in six patients. The follow-up period was 8.1 +/- 6.1 years. Acute pancreatitis and protein plug formation was observed in 18 (33.3%) and 11 (20.4%) of 54 patients showing primary cases, respectively. Both acute pancreatitis and protein plug formation were observed more frequently in children from 1 to 15 years of age (70.6% and 41.2%, respectively) than in adults (18.6% and 12.5%, respectively). Acute pancreatitis and/or protein plug formation developed in four (57.1%) of seven patients who underwent cystenterostomy. Protein plug formation in the residual cyst after cyst excision was observed in two patients, one of whom had undergone sphincteroplasty. Diabetes mellitus due to chronic pancreatitis developed in one patient who was diagnosed late. No other pancreatitis or protein plug recurred postoperatively in this series. Our results suggested that cystenterostomy did not resolve pancreatic complications of choledochal cysts, and that surgical sphincteroplasty was ineffective in preventing the recurrent protein plug formation in the residual duct. In conclusion, complete cyst excision and an early diagnosis are necessary to prevent the development of chronic or recurrent pancreatitis after surgery.

Acute Disease↗
PubMed2001

Cholangitis associated with cystic dilatation of the intrahepatic bile ducts after antireflux valve construction in biliary atresia.

An intussusception-type antireflux valve (ARV) has been introduced to prevent postoperative ascending cholangitis in the management of biliary atresia (BA). We investigated the characteristics of cholangitis in the management of BA using the ARV in 38 patients who had undergone an operation at our institution; 29 underwent ARV construction at the same time as portenterostomy (PEO) or hepaticojejunostomy. One patient underwent ARV construction for refractory cholangitis with cystic dilatation of the intrahepatic bile ducts (CDIB) long after the PEO. Five of 29 patients who had ARV construction developed CDIB complicated by severe, refractory cholangitis. One or two episodes of mild cholangitis were observed in 5 (20.8%) of 24 patients who did not show CDIB. An ARV created for postoperative recurrent cholangitis associated with CDIB was ineffective. Preoperative cholangitis associated with a type I choledochal cyst and CDIB was observed in 1 patient. In conclusion, the ARV was effective in preventing refractory cholangitis without CDIB, but ineffective in preventing cholangitis with CDIB. Our findings suggest that CDIB resulting from the ongoing process of BA could be a potential target of bacterial infection through other routes than bilioenteric reflux.

Bile Ducts, Intrahepatic↗
PubMed2001

Expression of angiogenic factors and tumor progression in human neuroblastoma.

PURPOSE: The growth and metastasis of malignant tumors is largely dependent on angiogenesis. Angiogenic factors produced by tumor cells are known to promote tumor angiogenesis. The aim of this study was to investigate which angiogenic factor is the most important in the progression of neuroblastoma (NB). PROCEDURE: The relative expression levels of vascular endothelial growth factor-A (VEGF-A), VEGF-C, basic fibroblast growth factor (bFGF), and platelet-derived endothelial growth factor (PD-ECGF/TP) were studied in 28 NB tumor specimens by real-time quantitative reverse transcriptase/polymerase chain reaction (RT-PCR). The relationships between the expression of these four angiogenic factors and stage, patient age, primary site, MYCN copy number, and lymph node metastasis were analyzed. RESULTS: High VEGF-A expression was correlated with stage 4 disease (blood-borne metastasis). No relationship between VEGF-A expression and age, primary site, MYCN copy number, or lymph node metastasis was found. The expression of VEGF-C, bFGF, or PD-ECGF/TP showed no correlation with stage, age, primary site, MYCN copy number, or lymph node metastasis. CONCLUSIONS: Our findings suggest that VEGF-A, but not VEGF-C, bFGF, or PD-ECGF/TP, may be associated with progression of NB. VEGF-A could be a target for antiangiogenic therapy for disseminated NB.

Angiogenesis Inducing Agents↗
PubMed2001

Mutational analysis of the BMP-1 gene in patients with gastroschisis.

BACKGROUND: Gastroschisis is a rare abdominal wall defect. Although the pathogenesis of gastroschisis is unknown, there is some evidence of the genetic etiology of gastroschisis. Recently, a functionally null deletion of the mouse bone morphogenic protein-1 (BMP-1) gene resulted in a phenotype that resembled a human neonate with gastroschisis. BMP-1 thus became the first potential candidate gene for gastroschisis. METHODS: To explore this possibility the authors collected blood samples from 11 patients who had gastroschisis. Mutational analysis of exons 2 to 15 of the human BMP-1 gene was performed using genomic polymerase chain reaction, single-strand conformation polymorphism analysis and direct sequencing methods. RESULTS: No mutation of the human BMP-1 gene was observed in any of these patients. CONCLUSION: Although heterogeneous etiologies might be proposed for gastroschisis, our results provide further evidence of a nongenetic etiology for gastroschisis. J Pediatr Surg 36:885-887.

Bone Morphogenetic Protein 1↗
PubMed2000

Biliary atresia with extrahepatic biliary cysts--cholangiographic patterns influencing the prognosis.

PURPOSE: Biliary atresia (BA) with extrahepatic biliary cysts (EHBC) has been recognized generally as "correctable" BA, which indicates a good prognosis. The variants of BA with EHBC according to cholangiographic findings and their outcomes were reviewed. METHODS: An EHBC was observed in 8 (20%) of 40 patients with BA who underwent operation at our institute. Intraoperative cholangiographic patterns included visualization of the intrahepatic bile ducts (type I BA with EHBC) in 6 patients and no visualization (type III BA with EHBC) in 2. Intrahepatic biliary cysts (IHBC) and EHBC were observed simultaneously in 2 patients diagnosed at older age. The follow-up periods ranged between 4 months and 20 years. RESULTS: Good bile drainage after a hepaticoenterostomy or portoenterostomy was obtained in all 6 patients with type I BA with EHBC. Two who showed IHBC on intraoperative cholangiography had complications caused by postoperative recurrent cholangitis, which led to a liver transplantation in 1. Revision after the portoenterostomy was required in 2 patients with type III BA with EHBC. One became jaundice free after revision, whereas the other died of hepatic failure without bile drainage. CONCLUSION: Intraoperative cholangiographic findings showing IHBC and type III BA are poor prognostic factors in patients with BA with EHBC.

Biliary Atresia↗
PubMed2000

Choledochal cyst associated with duodenal obstruction.

The association between congenital duodenal obstruction and concomitant choledochal cyst has not been reported, although duodenal obstruction is known to be associated with many other anomalies. The authors describe 2 patients with choledochal cyst with duodenal obstruction. In 1 patient, a diverticulum type of choledochal cyst was found within an annular pancreas. Cyst excision, choledochojejunostomy, and side-to-side duodeno-duodenostomy were performed. The other patient showed separated duodenal atresia and other multiple anomalies including imperforate anus. A choledochal cyst was noted at the time of duodeno-duodenostomy and sigmoid colostomy. Cyst-enterostomy was performed at the age of 8 months, but the patient died of multiple anomalies. Intraoperative cholangiography indicated an anomalous pancreatobiliary ductal junction (APBDJ). In both patients the bile in the cyst contained high levels of amylase, suggesting the presence of an APBDJ. An APBDJ is considered to play an etiologic role in the development of the choledochal cysts associated with duodenal obstruction.

Choledochal Cyst↗
PubMed1999

Laparoscopic resection of an adrenal neuroblastoma detected by mass screening that grew in size during the observation period.

Neuroblastomas (NB) identified by mass screening tests are characterized by benign features. Recently, laparoscopic resection has been applied to the treatment of patients with small adrenal NB (<2-3 cm). However, an increasing number of cases of small NB are followed without any treatment in Japan because many cases regress spontaneously. We describe a case of right adrenal NB detected by mass screening that increased in size during an observation period of 8 months. In this case, laparoscopic resection was performed successfully. The size of the tumor was 27 x 20 x 18 mm at diagnosis and 51 x 42 x 35 mm when it was excised. Small adrenal NB that do not regress during the observation period may require laparoscopic resection before they reach 5 cm in maximum diameter.

Adrenal Gland Neoplasms↗
PubMed1999

Hemizygous deletions of chromosome band 16q24 in Wilms tumor: detection by fluorescence in situ hybridization.

Loss of heterozygosity (LOH) for markers on chromosome arm 16q in Wilms tumor has been linked to an increased risk of treatment failure. We therefore postulated that fluorescence in situ hybridization (FISH) with probes from this region might enhance current strategies for identifying high-risk patients at diagnosis. In a blinded comparative pilot study of 19 Wilms tumor samples from 18 patients with favorable histology, FISH and DNA polymorphism analysis yielded concordant results in 14 cases, either retention (n = 6) or loss (n = 8) of chromosome arm 16q markers. Discordant findings in 4 of the 5 remaining cases resulted from detection of LOH, but no loss by FISH. Two of these cases, directly comparable at marker D16S422, appeared to have tumor-specific uniparental disomy, in that 2 copies of D16S422 and the 16 centromere were evident, despite LOH. In 2 other cases, the discrepancies could be explained by LOH confined to loci distal to the D16S422 locus. In the fifth case, FISH detected 2 distinct populations of tumor cells, one characterized by normal diploidy and the other by monosomy 16, whereas DNA polymorphism analysis failed to indicate LOH altogether. Thus, FISH confirmed the presence of allelic loss (hence, the possible location of biologically important tumor suppressor genes) on the distal long arm of chromosome 16 in cases of favorable-histology Wilms tumor, with the advantages of technical simplicity, successful analysis of samples that were otherwise uninformative by analysis of DNA polymorphisms, and the addition of internal controls for chromosomal aneusomy. We suggest that combined analysis of the chromosome 16q region in Wilms tumor by FISH and DNA polymorphism analysis would improve evaluations to identify high-risk patients who might benefit from alternative therapy.

Child↗
PubMed1999

Optical imaging of the spatiotemporal patterning of neural responses in the embryonic chick superior cervical ganglion.

Multiple-site optical recording of transmembrane potential changes with a voltage-sensitive dye was used to reveal the functional expression and developmental changes of the postsynaptic potentials in the early embryonic chick superior cervical ganglion. The ganglia were isolated from five- to 12-day-old chick embryos with preganglionic nerve fibres (vertebral and/or cervical carotic nerves) attached. The preparations were stained with a voltage-sensitive merocyanine-rhodanine dye (NK2761). Voltage-related optical (absorbance) changes were recorded simultaneously from 127 contiguous loci in the preparation, using a 12 x 12-element photodiode array. Optical changes having two components were evoked by preganglionic nerve stimulation. One component was the fast spike-like signal and another the delayed slow signal. The amplitude of the slow signal was decreased by repetitive stimulation, reduced by low external calcium ion concentrations and eliminated in the presence of manganese or cadmium ions. The slow signals were also eliminated in the presence of D-tubocurarine. Accordingly, we concluded that the slow signal corresponds to cholinergic excitatory postsynaptic potentials. In the five- and six-day-old superior cervical ganglia, only the fast optical signals (referred to as the action potentials) were recorded. Slow optical signals (referred to as the excitatory postsynaptic potentials) were detected from preparations older than seven days. The amplitude of the slow optical signal gradually increased, together with an expansion of the response area, as the developmental stage proceeded from seven to 10 days. To compare the distribution patterns of the neural responses evoked by stimuli applied to the cervical carotic and vertebral nerves, we have mapped and imaged the spatial patterning of the synaptic responses. In the maps, the positions of the peak size regions of the slow signals were assessed, and we found that there were differences in the location of these areas for the cervical carotic vs vertebral nerves. From these experimental results, we conclude that synaptic function within the chick superior cervical ganglion is initiated at the seven-day-old embryonic stage, and reaches a maximum level at 10 days. Synaptic transmission at these stages is mediated solely by nicotinic acetylcholine receptors. The spatial mapping of the synaptic responses reveals that the neural populations related synaptically to the cervical carotic and vertebral nerves are located separately within the ganglion, even at an early developmental stage.

Animals↗
PubMed1999

p27KIP1 deletions in childhood acute lymphoblastic leukemia.

The p27KIP1 gene, which encodes a cyclin-dependent kinase (CDK) inhibitor, has been assigned to chromosome band 12p12, a region often affected by cytogenetically apparent deletions or translocations in childhood acute lymphoblastic leukemia (ALL). As described here, fluorescence in situ hybridization (FISH) analysis of 35 primary ALL samples with cytogenetic evidence of 12p abnormalities revealed hemizygous deletions of p27KIP1 in 29 cases. Further analysis of 19 of these cases with two additional gene-specific probes from the 12p region (hematopoietic cell phosphatase, HCP and cyclin D2, CCND2) showed that p27KIP1 is located more proximally on the short arm of chromosome 12 and is deleted more frequently than either HCP or CCND2. Of 16 of these cases with hemizygous deletion of p27KIP1, only eight showed loss of HCP or CCND2, whereas loss of either of the latter two loci was uniformly associated with loss of p27KIP1. Missense mutations or mutations leading to premature termination codons were not detected in the coding sequences of the retained p27KIP1 alleles in any of the 16 ALL cases examined, indicating a lack of homozygous inactivation. By Southern blot analysis, one case of primary T-cell ALL had hemizygous loss of a single p27KIP1 allele and a 34.5-kb deletion, including the second coding exon of the other allele. Despite homozygous inactivation of p27KP1 in this case, our data suggest that haploinsufficiency for p27KIP1 is the primary consequence of 12p chromosomal deletions in childhood ALL. The oncogenic role of reduced, but not absent, levels of p27KIP1 is supported by recent studies in murine models and evidence that this protein not only inhibits the activity of complexes containing CDK2 and cyclin E, but also promotes the assembly and catalytic activity of CDK4 or CDK6 in complexes with cyclin D.

Adolescent↗
PubMed1998

Distinct modes of neuronal migration in different domains of developing cerebellar cortex.

As postmitotic neurons migrate to their final destinations, they encounter different cellular microenvironments, but functional responses of migrating neurons to changes in local environmental cues have not been examined. In the present study, we used a confocal microscope on acute cerebellar slice preparations to examine real-time changes in the shape of granule cells, as well as the mode and rate of their migration as they transit different microenvironments. The rate of granule cell movement is fastest in the molecular layer, whereas their elongated somata and long leading processes remain in close contact with Bergmann glial fibers. Cell movement is slowest in the Purkinje cell layer after granule cells detach from the surface of Bergmann glia and the somata become transiently round, whereas the leading processes considerably shorten. Surprisingly, after entering the internal granular layer, granule cells re-extend both their somata and leading processes as they resume rapid movement independent of Bergmann glial fibers. In this last phase of migration, described here for the first time, most granule cells move radially for >100 micron (a distance comparable to that observed in the molecular layer) until they reach the deep strata of the internal granular layer, where they become rounded again and form synaptic contacts with mossy fiber terminals. These observations reveal that migrating neurons alter their shape, rate, and mode of movement in response to local environmental cues and open the possibility for testing the role of signaling molecules in cerebellar neurogenesis.

Aging↗
PubMed1998

Congenital mediastinal dumbbell neuroblastoma with spontaneous regression of liver metastases.

We report a patient with a congenital mediastinal dumbbell neuroblastoma (NB) presenting as respiratory distress at birth rather than a neurologic deficit. The tumor did not respond to low-dose chemotherapy, but radiotherapy and surgery were effective. The patient was observed postoperatively without further therapeutic intervention considering the favorable biologic factors despite the appearance of liver metastases, which ultimately regressed spontaneously. The authors believe that most congenital NBs have favorable outcomes with a possibility of spontaneous regression, and that an understanding of the biologic features of tumors is important to avoid overtreatment of lesions with a favorable prognosis. Keywords Congenital neuroblastoma. Dumbbell tumor. Liver metastasis. Spontaneous regression

Combined Modality Therapy↗
PubMed1998

A regional gradient of cardiac intrinsic rhythmicity depicted in embryonic cultured multiple hearts.

We used optical methods to examine the spatial gradient of intrinsic rhythmicity in early-stage multiple-heart chick embryos. The latter were induced experimentally in whole-embryo culture. The embryos were cut microsurgically through the tissue of the anterior intestinal portal at the 5- to early 7-somite developmental stage. Spontaneous electrical activity in 4 to 6 segmented hearts, during the 7- to 10-somite stages of development, were monitored simultaneously by means of multiple-site optical recordings of membrane potential activity, using a voltage-sensitive merocyanine-rhodanine dye (NK2761). Each segment of the heart exhibited its own inherent rhythmicity. In quadruple hearts, the order of the rhythmicity was often left-caudal segment>right-caudal segment>left-cephalic segment>right-cephalic segment; the heart rate in the left-caudal segment was often faster than that in the other segments. An atypical pattern of "bursting" rhythm was observed in the cephalic segments suggesting that, in these segments, the development of rhythmicity is relatively poor. These findings strongly emphasize the concept that, in the early phases of cardiogenesis, the formation of a regional gradient of pacemaker activity (i.e. a spatial gradient of intrinsic rhythmicity) results in the functional self-organization of the pacemaking area.

Action Potentials↗
PubMed1998

Staged silo repair of gastroschisis with preservation of the umbilical cord.

BACKGROUND: The optimal surgical approach for gastroschisis remains controversial, although primary closure after vigorous stretching of the abdominal wall and decompression of the intestinal contents is currently preferred. METHODS: Between 1984 and 1997, 24 newborns with gastroschisis were treated at Saitama Children's Medical Center. The average gestational age was 37.3 weeks, and the average birth weight was 2,285 g. One patient had the associated anomaly of intestinal atresia and short bowel. Rupture of the intestines during delivery was noted in one patient. The authors applied their nonaggressive staged repair using a prosthetic silo with preservation of the umbilical cord in 20 of the 24 cases (83.3%). Primary closure with preservation of the umbilical cord was performed in the remaining four cases (16.7%). In these patients, the gastroschisis was mild. RESULTS: In the 20 cases treated by staged repair, the average interval between the first and second operation was 9.8 days. Mechanical ventilation was not required in 16 of 20 (80%) patients treated by staged repair, or in two of four (50%) patients treated by primary repair. The number of days to the first feeding averaged 14.6 days in 23 cases, excluding the patient with short bowel syndrome who required continuous total parenteral nutrition (TPN). TPN through a central venous catheter was required in 3 of 23 patients (13.0%). The overall average hospital stay was 55.1 days. Survival was 24 of 24 or 100%. Complications included perforation of the intestines, gastric bleeding, ventral hernia, and wound infection. No infections were associated with the prosthetic silo. All of the patients had a satisfactory cosmetic outcome. Recent advances in neonatal intensive care, including antibiotic therapy, reduced the possibility of infection. CONCLUSIONS: This staged repair of gastroschisis was simple and safe, neither requiring experienced surgical judgment nor complicated postoperative management, and achieved satisfactory results. Furthermore, preservation of the umbilical cord provided an improved cosmetic appearance.

Abdominal Muscles↗