Biomedical subjects

H Komuro

Publications and source records attributed to H Komuro.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1998

Fluorescence in situ hybridization analysis of chromosome 1p36 deletions in human MYCN amplified neuroblastoma.

BACKGROUND/PURPOSE: Deletion of the short arm of chromosome 1 (1p) is one of the poor prognostic factors in human neuroblastomas. Recent studies have suggested that one or more of the neuroblastoma tumor suppressor genes reside in this region and have identified the shortest region of overlap (SRO) on 1p36. The purpose of this study was to examine deletions of 1p in human neuroblastomas by fluorescence in situ hybridization (FISH). METHODS: Two-color FISH analysis was performed to detect chromosome 1p36 abnormalities in 42 MYCN-amplified neuroblastomas. Four different probes from the 1p36 region, the E2F2, NPPA, D1S160, and CDC2L1 loci were used for detection of 1p abnormalities. A repeat sequence probe, which is specific for the heterochromatic region of chromosome 1 (pUC1.77), was used as a control. RESULTS: Large deletions of 1p36 were observed in 31 (73.8%) of 42 tumors, whereas the remaining 11 (26.2%) showed no deletion. In these 11 tumors, a translocation of 1p was found in one and a duplication of 1p was detected in another. CONCLUSIONS: A strong correlation between 1p abnormalities and MYCN amplification was found in this study. MYCN-amplified neuroblastomas were found to show large deletions of 1p encompassing the SRO. FISH provided a rapid and reliable method to detect hemizygous deletions of 1p.

Child, Preschool↗

PubMed1998

Orchestration of neuronal migration by activity of ion channels, neurotransmitter receptors, and intracellular Ca2+ fluctuations.

The real-time observation of cell movement in acute cerebellar slices reveals that granule cells alter their shape concomitantly with changes in the mode and rate of migration as they traverse different cortical layers. Although the origin of local environmental cues responsible for these position-specific changes in migratory behavior remains unclear, several signaling mechanisms involved in controlling granule cell movement have emerged. The onset of one such mechanism is marked by the expression of voltage-gated ion channels and neurotransmitter receptors in postmitotic cells prior to the initiation of their migration. Granule cells start their radial migration after the expression of N-type Ca2+ channels and the N-methyl-D-aspartate subtype of glutamate receptors on the plasmalemmal surface. Blockade of the channel or receptor activity significantly decreases the rate of cell movement, indicating that the activation of these membrane constituents provides an essential signal for the translocation of granule cells. Another signal that controls the rate of cell migration is embedded in the combined amplitude and frequency components of Ca2+ fluctuations in the somata of migrating granule cells. Interestingly, each phase of Ca2+ fluctuation controls a separate phase of saltatory movement in the granule cells: The cells move forward during the phase of transient Ca2+ elevation and remain stationary during the troughs. Consequently, the changes in the amplitude and frequency components of Ca2+ fluctuations directly affect granule cell movement: Reducing the amplitude or frequency of Ca2+ fluctuations slows down the speed of cell movement, while the enhancement of these components accelerates migration. These findings suggest that signaling molecules present in the local cellular milieu encountered on the migratory route control the shape and motility of granule cells by modifying Ca2+ fluctuations in the soma through the activation of specific ion channels and neurotransmitter receptors.

Animals↗

PubMed1997

Relationship between duration of rheumatoid arthritis before knee joint surgery and HLA-DRB1 alleles: a retrospective study.

OBJECTIVE: To examine whether genetically determined factors can be used as predictors of requirement for knee joint surgery in the early phase of rheumatoid arthritis (RA). METHODS: We determined HLA-DRB1 alleles in 322 patients with seropositive RA by polymerase chain reaction and allele specific oligonucleotide probe techniques. Patients were classified into 3 groups (S/S, S/N, and N/N) based on their possession of two, one or no susceptibility alleles of RA, respectively. The stage of radiographic change in the knee joint determined using Larsen's standard film was compared to results of genotyping. Duration of RA before joint surgery in the 3 groups was also compared retrospectively. RESULTS: The median number of years to develop to stages I, II, III, and IV and the number of years of disease duration before total knee arthroplasty (TKA) were significantly shorter in the S/S group than in the S/N and N/N groups (p < 0.05). CONCLUSION: TKA was required earlier in the S/S group than in the S/N and N/N groups. This finding will affect planning of surgical management for RA based on anticipated courses.

Adult↗

PubMed1996

Intracellular Ca2+ fluctuations modulate the rate of neuronal migration.

Transient elevations of intracellular Ca2+ levels play critical roles in neuronal development, but such elevations have not been demonstrated in migrating neurons. Here, we show that the amplitude and frequency components of Ca2+ fluctuations are correlated positively with the rate of granule cell movement in cerebellar microexplant cultures. Moreover, depression of the amplitude and frequency components of Ca2+ fluctuations by blockade of Ca2+ influx across the plasma membrane results in a reversible retardation of cell movement. These results indicate that the combination of amplitude and frequency components of intracellular Ca2+ fluctuations may provide an intracellular signal controlling the rate of neuronal cell migration.

Animals↗

PubMed1995

Lack of correlation of N-myc gene amplification with prognosis in localized neuroblastoma: a Pediatric Oncology Group study.

Multiple copies of N-myc proto-oncogene are only rarely detected in localized neuroblastomas (NBs), and the prognostic relevance of amplification in this subset of patients is not clear. We analyzed a series of 850 children with NB admitted to a Pediatric Oncology Group NB Biology Study and identified six patients with localized NBs harboring N-myc gene amplification. Three patients whose tumors showed favorable histology by Shimada classification and low-risk histological features according to the Joshi classification have remained disease-free, whereas two of three patients with unfavorable histology tumors have developed recurrent disease. Although earlier studies have indicated that N-myc amplification is associated with diploid DNA content, flow cytometric analysis revealed that only two of the localized tumors contained stem lines with diploid DNA content. Loss of chromosome 1p was not detected by fluorescence in situ hybridization in the two tumors examined. N-myc protein was detected by immunohistochemical studies in four of the five NBs analyzed. However, N-myc protein was not visualized in one of the tumors with stroma-rich histology, and Western blot analysis revealed only low levels of N-myc protein expression in another NB with favorable histology. These studies indicate that the presence of N-myc amplification in localized NBs does not necessarily portend an adverse outcome. Furthermore, the biological features of this subset of N-myc-amplified NBs appear to differ from those of more advanced N-myc-amplified tumors.

Child↗

PubMed1995

The role of receptor/channel activity in neuronal cell migration.

Confocal laser microscopy, in conjunction with carbocyanine dyes and calcium-sensitive fluorescent indicators, was used in slices and explant cultures of developing cerebellum to study cellular mechanisms underlying a motility of neuronal cell migration. The results indicate that a combination of voltage- and ligand-activated ion channels cooperatively regulates Ca2+ influx into the migrating cells. We suggest that molecules, present in the local cellular milieu, affect cell motility by activating specific ion channels and second messengers that influence polymerization of stiff and contractile cytoskeletal proteins. This early interaction between postmitotic neurons and surrounding cells controls the rate of their movements, sculpts their shapes, establishes their positions, and, therefore, indirectly determines their identities to prior formation of synaptic connections.

Animals↗

PubMed1995

Dynamics of granule cell migration: a confocal microscopic study in acute cerebellar slice preparations.

Real-time examination of Dil-labeled, immature granule cells in cerebellar slice preparations reveals several temporal and cytological aspects of neuronal migration that have not been observed in previous in vivo or in vitro systems. Using confocal microscopy we have obtained evidence that rates of cell movement depend critically on the age of the cerebellum. Although there were considerable variations in the speed of individual cells, the average rate of cell migration increased systematically from 9.6 +/- 3.0 microns/hr in cerebella from 7-d-old mice to 18.0 +/- 2.9 microns/hr in cerebella from 13-d-old mice. Consequently, granule cells traversed the developing molecular layer within a relatively constant time period despite the doubling in width of the molecular layer during the second week of postnatal life. Granule cell movement was characterized by alternations of short stationary phases with movement in a forward or backward direction. The net displacement of a cell depended on the duration and frequency of these phases as well as on the speed of movement. Changes in the relative position of Dil crystals attached to the surface of granule cells suggested the existence of a complex topographical flow of plasma membrane during migration. Although a large portion of the plasma membrane seemed to move in register with the nucleus and surrounding cytoplasm, new membrane appeared to be incorporated primarily at the leading process. However, the pattern of membrane flow at the interface between migrating neurons and Bergmann glial fibers could not be determined, since these sites could not be labeled by Dil crystals. The present results are in harmony with the concept that multiple cellular/molecular mechanisms may be engaged in granule cell migration.

Aging↗

PubMed1994

Effects of CPT-11 (a unique DNA topoisomerase I inhibitor) on a highly malignant xeno-transplanted neuroblastoma.

Although many advances have been made in the management of neuroblastoma, the prognosis of patients with advanced neuroblastoma remains poor, and constant efforts are being made to search for newer effective drugs. CPT-11 is a newly developed derivative of camptothecin and shows a unique anti-tumor activity by inhibiting DNA topoisomerase I. In this study the effects of CPT-11 on a human neuroblastoma xenograft, TNB9, were investigated according to the standard Battelle Columbus Laboratories protocol. TNB9 is one of the most malignant strains of neuroblastoma, showing a homogeneously staining resion (HSR) on chromosome 20 and 80-fold amplification of the N-myc gene. This study disclosed that CPT-11 was highly effective against TNB9. Maximum inhibition rate (IR) was 72.5% at a standard dose and 52.8% even at half the dose. No nude mouse used in this study lost weight after an administration of CPT-11. Plasma pharmacokinetics of CPT-11 administered in this experimental model were compared to that in clinical patients. Our data suggested that CPT-11 might be a promising new drug in the treatment of high-risk neuroblastoma patients and encouraged us to employ CPT-11 in the protocol of the Study Group of Japan.

Animals↗

PubMed1994

Intralesional corticosteroid injection with short-term oral prednisolone for infantile hemangiomas of the eyelid and orbit.

Infants with hemangiomas of the eyelid and orbit are at risk for amblyopia and refractive errors. Several methods of treatment for these tumors have been associated with complications and limitations. Five infants with these hemangiomas were treated by intralesional corticosteroid injection combined with short-term oral prednisolone. In an attempt to eliminate complications, corticosteroid injections were administered. In the cases of orbital hemangioma, ultrasonography guidance was used to assist the injection. This treatment is safe, simple, and effective for infants. In addition, complications are minimized.

Administration, Oral↗

PubMed1994

Partial liver transplantation from a living donor: experimental research and clinical experience.

Partial liver transplantation (PLTR) was studied experimentally, using 60 monkeys (20 recipients, 20 donors, 20 blood donors). The left lobe of the donors was transplanted orthotopically, using a veno-venous bypass catheter that was inserted in the portal vein and the other side passed through the hepatic portion of the inferior vena cava. The donor survival rate at 1 week was 70%. Seven recipients survived for more than 58 hours (58, 60, 64, 68, 72, 110, and 252 hours), and 13 died within 48 hours of surgery because of postoperative complications. Clinical living related liver transplantation (LRLT) was performed between June 1990 and March 1992 on six patients with biliary atresia and on one with liver cirrhosis and hepatocellular carcinoma. In all, the father's left lobe was transplanted orthotopically. Cyclosporine, azathioprine, and methyl prednisolone were administered. In addition, FK-506 was given to two patients in whom rejection was observed; one died 37 days after surgery because of acute rejection followed by systemic cytomegalovirus infection. The other six patients have survived for 8 to 29 months since transplantation. All six have been discharged from the hospital and are enjoying normal daily life. The postoperative course of all donors was uneventful. They were discharged 2 weeks after the operation and returned to their jobs in 2 months. The authors conclude that PLTR from a living donor is a promising therapeutic alternative to liver transplantation from a cadaver.

Adult↗

PubMed1994

Primary chemotherapy for children with rhabdomyosarcoma of the 'special pelvic' sites: is preservation of the bladder possible?

Twenty-one children with rhabdomyosarcoma involving the "special pelvic" sites, defined as such occurring in the bladder, prostate, vagina and uterus, were treated with primary surgery between 1969 and 1977, and with primary chemotherapy beginning in 1978. Among 11 patients in the latter group who were placed in Clinical Group III (according to the classification of the US Intergroup Rhabdomyosarcoma Study (IRS), six showed partial response (PR) and underwent tumorectomy by radical surgery an average of 6 months after the start of treatment, and three showed complete response (CR) and were treated with further chemotherapy in the hope that cystectomy could be avoided. However, in the latter group, the tumor recurred (39 months, 35 months, and 27 months later), and all eventually underwent total cystectomy. Seven of the nine long-term survivors underwent total cystectomy and have premanent urinary-cutaneous stomas. Two had tumor-free bladders, but function was impaired in one because of the effect of irradiation. Normal function was preserved in only one patient in the series, whose tumor was located at the dome of the bladder. To preserve bladder function in children with rhabdomyosarcoma in these sites, more effective forms of chemotherapy will be required.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Recognition, adhesion, transmembrane signaling and cell motility in guided neuronal migration.

Recent studies indicate that migration of neurons from their place of origin to their final destination requires the orchestration of multiple molecular events, including the selection of a pathway by cell recognition receptors, the formation of adhesive interactions with cellular and extracellular substrates through multiple adhesion molecules and the activation of specific ion channels and receptors that provide second messenger mediated signals for the diverse cellular mechanisms involved in cell motility. New approaches allow for the examination of the role of individual molecular components that mediate these processes.

Animals↗

PubMed1994

Congenital diaphragmatic hernia treated by perinatal stabilization.

The delay of surgery in conjunction with high-frequency oscillation ventilation combined with preoperative stabilization is a standard treatment for congenital diaphragmatic hernia neonates in the high-risk group. A new protocol of perinatal stabilization with this preoperative stabilization has been developed at the University of Tokyo Hospital. The most important components of this method of perinatal stabilization are cesarean section and the injection of morphine and pancuronium through the umbilical vein prior to ligation of the umbilical cord. In order to benefit from this treatment, congenital diaphragmatic hernia patients should be diagnosed antenatally by ultrasonography and be delivered by cesarean section. This protocol of perinatal stabilization appears effective in congenital diaphragmatic hernia patients.

Fatal Outcome↗

PubMed1993

Mutations of the p53 gene are involved in Ewing's sarcomas but not in neuroblastomas.

We have investigated the frequency of p53 gene mutations in Ewing's sarcoma (ES) and neuroblastoma (NB) by using polymerase chain reaction-single strand conformation polymorphism analysis for genomic DNA or complementary DNA generated from total RNA. Mutations of the p53 gene were found in six of seven ES cell lines: a missense mutation of TGC (Cys)-->TAC (Try) at codon 141 in one, a missense mutation of CGT (Arg)-->TGT (Cys) at codon 273 in one, a missense mutation of TGC (Cys)-->TTC (Phe) at codon 176 in three, and one base deletion of CGC-->CG at codon 283 in one. Further analysis of 14 ES and related primary tumors showed mutations of the p53 gene in only two: one base insertion of CCG-->CCCG at codon 152 in one and a missense mutation of GGC (Gly)-->GTC (Val) at codon 154 in the other. Both of the two tumors were obtained from patients with an advanced stage disease. Three of the eight ESs with mutations of the p53 gene showed the same missense mutation at codon 176, suggesting the mutational hot spot of the p53 gene in ESs. In contrast to ES, none of 6 NB cell lines or 48 NB tumors including advanced-stage ones with or without N-myc amplification showed any aberration of the p53 gene. Our findings suggest that mutations of the p53 gene in ES might represent late genetic events related to tumor progression, and that aberrations of the p53 gene might not be involved in the development or the progression of NB.

Adolescent↗

PubMed1993

Modulation of neuronal migration by NMDA receptors.

The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is essential for neuronal differentiation and establishment or elimination of synapses in a developing brain. The activity of the NMDA receptor has now been shown to also regulate the migration of granule cells in slice preparations of the developing mouse cerebellum. First, blockade of NMDA receptors by specific antagonists resulted in the curtailment of cell migration. Second, enhancement of NMDA receptor activity by the removal of magnesium or by the application of glycine increased the rate of cell movement. Third, increase of endogenous extracellular glutamate by inhibition of its uptake accelerated the rate of cell migration. These results suggest that NMDA receptors may play an early role in the regulation of calcium-dependent cell migration before neurons reach their targets and form synaptic contacts.

2-Amino-5-phosphonovalerate↗

PubMed1993

A new operational approach for the piriform sinus fistula.

It has been well documented that piriform sinus fistulae often cause suppurative thyroiditis; however, when a piriform sinus fistula does not present this symptom, making a correct diagnosis is very difficult. We have experienced 11 cases of a piriform sinus fistula. The conventional operational approach was performed in the initial eight patients, among which there were four recurrences in two patients. Therefore, a new operational approach was introduced for the three most recent cases and one recurrent case. First, the existence of the internal orifice of the fistula is confirmed with a laryngoscope, after which a transverse incision on the neck is made and the abscess dissected. The side wall of the piriform sinus is then opened with the help of a laryngoscope and the bottom part of the mucosa of the sinus transected with the internal orifice of the fistula, after which the fistula is removed en bloc with the bottom part of the sinus and abscess cavity. Using this operation, we experienced no complications and there has been no recurrence so far.

Adolescent↗

PubMed1993

Optical monitoring of early appearance of spontaneous membrane potential changes in the embryonic chick medulla oblongata using a voltage-sensitive dye.

Using a voltage-sensitive merocyanine-rhodamine dye (NK2761) and a 12 x 12-element photodiode matrix array, we recorded optically spontaneous membrane potential changes in a slice preparation from the embryonic chick brain stem during early development. The spontaneous optical signals, related to membrane potential changes, showed a simple monophasic shape with a relatively long duration, and they were synchronized among the different regions in the medulla oblongata. The spontaneous signals were first detected from seven-day-old embryos, and were not present in six-day-old embryos. The spontaneous signals appeared sporadically, and their frequency was very low. Three modes of optical signals termed "singlet-mode", "doublet-mode", and "triplet-mode" were observed. In the doublet- and triplet-modes, the spatial pattern of the first signal was primarily similar to that of the singlet-mode signal, whereas the signal size and spatial extent of the second and third signals appeared to decay.

Animals↗