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Biomedical subjects

K Morishima

Publications and source records attributed to K Morishima.

At least 19 recordsLinked to original sources

The forkhead-associated domain of NBS1 is essential for nuclear foci formation after irradiation but not essential for hRAD50[middle dot]hMRE11[middle dot]NBS1 complex DNA repair activity.

NBS1 (p95), the protein responsible for Nijmegen breakage syndrome, shows a weak homology to the yeast Xrs2 protein at the N terminus region, known as the forkhead-associated (FHA) domain and the BRCA1 C terminus domain. The protein interacts with hMRE11 to form a complex with a nuclease activity for initiation of both nonhomologous end joining and homologous recombination. Here, we show in vivo direct evidence that NBS1 recruits the hMRE11 nuclease complex into the cell nucleus and leads to the formation of foci by utilizing different functions from several domains. The amino acid sequence at 665-693 on the C terminus of NBS1, where a novel identical sequence with yeast Xrs2 protein was found, is essential for hMRE11 binding. The hMRE11-binding region is necessary for both nuclear localization of the complex and for cellular radiation resistance. On the other hand, the FHA domain regulates nuclear foci formation of the multiprotein complex in response to DNA damage but is not essential for nuclear transportation of the complex and radiation resistance. Because the FHA/BRCA1 C terminus domain is widely conserved in eukaryotic nuclear proteins related to the cell cycle, gene regulation, and DNA repair, the foci formation could be associated with many phenotypes of Nijmegen breakage syndrome other than radiation sensitivity.

Amino Acid Sequence↗

Microsatellite-centromere mapping in the loach, Misgurnus anguillicaudatus.

Primer sets for 15 polymorphic microsatellite loci were developed in the loach, Misgurnus anguillicaudatus (Cobitidae) by molecular cloning and sequencing techniques. Mendelian inheritance was confirmed for the 15 loci by examining the genotypic segregation produced with the primer sets in two full-sib families. The loci were mapped in relation to their centromere in four gynogenetic diploid lines, which were induced by inhibition of the second meiotic division after fertilization with genetically inert sperm. Microsatellite-centromere recombination rates ranged between 0.06 and 0.95 under the assumption of complete interference. Thus, these loci are distributed from the centromeres to the telomeres of their respective chromosomes. The success of mitotic gynogenesis, produced by suppression of the first cleavage, was verified by homozygosity at three diagnostic microsatellite loci that exhibited high gene-centromere meiotic recombination rates in the same family. The differences in heterozygosity levels observed with these markers were attributed to differences in the temporal application of heat shock following inert sperm activation.

Animals↗

Expression of full-length NBS1 protein restores normal radiation responses in cells from Nijmegen breakage syndrome patients.

Cells from Nijmegen breakage syndrome (NBS) display multiple phenotypes, such as chromosomal instability, hypersensitivity to cell killing from ionizing radiation, and possibly abnormal cell cycle checkpoints. NBS1, a gene mutated in NBS patients, appears to encode a possible repair protein, which could form the foci of a sensor-like molecular complex capable of detecting DNA double strand breaks, however, it has no kinase domain for signaling DNA damage. Here, we report that the stable expression of NBS1 cDNA in NBS cells after transfection results in the complete restoration of foci formation in the nucleus, and in normal cell survival after irradiation. The prolonged G2 block observed after irradiation was also abolished by expression of NBS1, providing additional confirmation that the G2 checkpoint is abrogated in NBS cells. These results suggest that a defective NBS1 protein could be the sole cause of the NBS phenotype, and that NBS1 likely interacts with another protein(s) to produce the entire range of NBS phenotypic expression.

Base Sequence↗

Banding of the pulmonary trunk in preparation for a Fontan operation.

Banding of the pulmonary trunk is an important surgical procedure for patients who have congenital cardiac malformations with unrestricted pulmonary flow. We propose a new concept for determining in such circumstances the most appropriate length of the band used to constrict the pulmonary trunk in preparation for a Fontan operation. We studied 14 patients undergoing banding of the pulmonary trunk and measured the following parameters: diameter of aorta, diameter of pulmonary trunk, length of pulmonary arterial band and maximum flow velocity across the banded segment. We calculated an index from our original parameter based on the formula; length of band/(diameter of aorta diameter of pulmonary trunk). The diameter of aorta was 9.5 +/- 1.4 mm, and that of the pulmonary trunk was 9.6 +/- 2.3 mm. The length of the band was 16.5 +/- 3.4 mm, giving a calculated index of 0.188 +/- 0.038. The maximum flow velocity was 4.02 +/- 0.46 m/s. No correlation was found between the length of the band and body weight, and also no correlation was found between the length of the band and maximum flow velocity. The calculated index had a negative correlation with the maximum velocity of flow across the band (y = -8.13x +/- 5.56, R = 0.74, p < 0.01). We believe that the proposed index is a useful guide in determining the length of a pulmonary band when preparing patients for a Fontan operation.

Cardiac Catheterization↗

[One-stage repair of interrupted aortic arch with selective cerebral perfusion].

To minimize the neurological compromise after the circulatory arrest, the selective cerebral perfusion could be beneficial. We underwent one-stage repair of the interrupted aortic arch (IAA) with various intracardiac anomalies for the six patients, age ranging from 12 days to 4 months, by using the selective cerebral perfusion. Cardiopulmonary bypass was established by using two-way arterial cannulation supported by the two respective pump systems, one of which utilized the EPTFE graft anastmosed to either the bracheocephalic artery or the right subclavian artery and second of which enrouted through the arterial ductus to the descending aorta. The cerebral perfusion during the circulatory arrest for the aortic arch repair was maintained by the selective perfusion via EPTFE graft with 10 ml/kg/min blood flow. After the completion of the arch repair, the total system perfusion was restarted through the graft and the repair of the intracardiac anomalies was followed. Of six, no operative death or neurological complications related to the operation were found. The clinical neurological evaluation after operation also demonstrated the normal for the age. In conclusion, the selective cerebral perfusion by using the EPTFE graft during the circulatory arrest might decrease the risk of brain damage.

Aorta, Thoracic↗

[A case of severe cytomegalovirus infection after the repair of coarctation of aorta].

We report a 2-month-old boy without any immuno-compromised diseases, who suffered from the severe cytomegalovirus (CMV) infection after the subclavian flap aortoplasty and pulmonary artery banding for coarctation complex. He underwent the operation at 2 months old and received 2 units of irradiated packed red blood cells before and after the surgery. His postoperative course was uneventful but the interstitial pneumonitis, until he developed watery diarrhea 10 days after the surgery following hepatitis with the marked hepatomegaly 3 weeks after. Since CMV infection was confirmed as the cause of the pneumonitis, enterocolitis and hepatitis, he was initially treated by gamma-globulin with the high CMV titer at a dose of 200 mg/kg/day for 2 days and ganciclovir at a dose of 10 mg/kg/day for 14 days. Because of the persistent CMV infection, he needed two more treatments of ganciclovir at the same dosage and gamma-globulin once a week for 2 months. He finally recovered from severe CMV infection 5 months after the above treatments. In conclusion, the severe CMV infection can occur by blood transfusion even in the surgical case with normal immune system. If one finds pneumonitis, hepatitis or enterocolitis after any type of surgery with history of blood transfusion, CMV infection should be suspected as the cause of these diseases.

Antiviral Agents↗

Gender differences in effects of 20 days horizontal bed rest on muscle strength in young subjects.

Gender differences in the effect of 20 days bed rest (BR) on muscle strength were evaluated in voluntary 11 male and 7 female students. Maximum Isometric Voluntary Contractions (MVC) of 4 right arm muscles (RAM), 5 right leg muscles (RLM), and 2 body trunk muscles were measured with an isometric dynamometer, respectively. Muscle masses (MM) of right arm and leg and body trunk were determined by dual energy X-ray absorptiometry, respectively. The maximum cross sectional area (CSAmax) of right m. quadriceps femoris was measured by magnetic resonance imaging. Elbow flexion MVC in males and all MVC of RLM except knee flexion in both males and females were decreased (p<0.05), but elbow extension MVC in females was increased (p<0.05), while all of other MVC only tended to decrease. However, the decrements in leg MVC were not correlated to the leg MM, and also the decrement in knee extension was not correlated to the CSAmax of m. quadriceps. The reduction of MVC of antigravity muscles might be caused not only by a decrease in MM but also by other factors. The greater decrements of leg MVC during BR were the higher initial level in males, but the inverse was observed in females. However, this discrepancy between males and females cannot be explained in the present study.

Adolescent↗

Effects of 20 days horizontal bed rest on maintaining upright standing posture in young persons.

The effects of 20 days horizontal bed rest (BR) on postural reflex were studied by measuring fluctuation of center of gravity in the body during two legs or one leg upright standing in 10 young volunteers. The fluctuation was decided as total moving distance of the center recorded during 60sec standing on a force plate. The stability was measured by the moved area. After BR, the moving distance increased during two legs standing with open eyes (p<0.05), but statistically unchanged with closed eyes. The moving area decreased during right one-leg standing with closed eyes (p<0.05), but unchanged during left one-leg standing. Despite with open eyes the increased distance suggested that postural reflexes to maintain upright position were probably decreased by increased unsuitable feedback informations from the visual receptor deconditioning during BR. The decreased area during right one-leg standing with closed eyes also suggested that the declined standing posture reflex was probably related to more rapidly lowered functions for maintaining standing position in the dominating leg than in the other.

Adult↗

Effects of 20 days horizontal bed rest on kinesthesia during knee flexion and two-point discrimination in skin of young subjects.

Investigating the effect of 20 days bed rest (BR) on kinesthesia and two-point discrimination, 10 young volunteers participated in this study as subjects. Angle position sensation of right knee was measured in the prone position during flexion and extension monitored by a goniometer after two-point discrimination in skin was determined on the same lower leg. Flexed constant error was unchanged but directional constant error and absolute error were increased after BR (p<0.05). Two-point discrimination was unchanged after BR, which brought about a decline of the orientation of moving the joint indicated as over shooting of the angle during knee flexion, while it did not affect superficial sensation observed by two-point discrimination. Probably, an adjustment of deep sensation to the knee joint is lowered by the reduction in kinesthesia as well as the sensory disturbance during BR, which is independent on information from superficial sensation.

Adult↗

[Successful repair of a newborn case with total anomalous pulmonary venous connection presenting hemodynamically common pulmonary vein atresia].

Common pulmonary vein atresia is a very rare from of congenital cardiac anomaly in which the common chamber of pulmonary veins has no direct communication to the heart or systemic venous system. We report here on one-day-old boy with total anomalous pulmonary venous connection having severe stenosis (sized less than one millimeter in diameter) of vertical vein between common pulmonary vein and superior vena cava. His anatomic feature was considered as a spectrum between common pulmonary vein atresia and total anomalous pulmonary venous connection because of almost atretic draining vertical vein. His clinical presentation and hemodynamic characteristics were the same as common pulmonary vein atresia. He underwent an emergent anastomosis of common pulmonary vein to left atrium at 33 hours after birth under cardiopulmonary bypass, cross-sectional echocardiography and Doppler color mapping. He was discharged home two months after the surgery. Cardiac catheterization after six months revealed normal cardiac function without any evidence of pulmonary venous chamber stenosis. To improve the outcome of surgical intervention for this life-threatening cardiac anomaly, immediate the precise diagnosis using echocardiography followed by emergent surgical correction is in dispensable.

Cardiac Surgical Procedures↗

A rare case of a kidney with an widely opened hilus and supernumerary renal vessels.

This is an autopsy case reporting variation in the left kidney of a 87-year-old Japanese woman. The kidney in question possessed a widely opened hilus, was located in a lower position than usual, and was supplied and drained by multiple vessels. Major findings are as follows: 1. The left kidney, diamond-shaped, was situated lower than usual. 2. The hilus of this kidney was widely opened, facing anteriorly. 3. It was supplied by, in addition to an ordinal renal artery, 4 supernumerary arteries arising from the lower portion of the abdominal aorta and was drained by one ordinary and one supernumerary vein, the latter of which opened into the lumbar vein.

Aged↗

[Cavernostomy and muscle plombage with the pedicled latissimus dorsi and serratus anterior flap for recurrent large bullae with infection: a case report].

A 70-year-old male, who suffered from infection by MRSA and Aspergillus of the recurrent large bullae, was operated on cavernostomy for space sterilization. About three months later he underwent muscle plombage with the pedicled latissimus dorsi and serratus anterior flap. These muscles are ideal to place in open wound in the thorax because of the following reasons: These have the ability to eliminate local infection, a sufficient length and volume to obliterate an open cavity. And transposition of these muscles cause minimal functional upper extremity disability. Therefore, we considered that this technic was useful for the case of an infectious intrathoracic cavity with many bronchial fistulas.

Aged↗

Determination of a new calcium antagonist, sesamodil fumarate (SD-3211), and its metabolite in plasma by liquid chromatography with electrochemical detection.

A sensitive and selective high-performance liquid chromatographic method is described for the determination of a novel calcium antagonist, (+)-(R)-3,4-dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[(3,4- methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo-2H- 1,4-benzothiazine hydrogen fumarate (sesamodil fumarate; JAN, SD-3211, I), and its N-desmethylated metabolite (II) in plasma. Compounds I and II and an internal standard were isolated from plasma by solid-phase and liquid-liquid extraction. The extract was chromatographed on a reversed-phase C18 column, and the compounds of interest were detected by dual coulometric electrodes operated in an oxidative screen mode. The limit of determination for both I and II was at least 0.4 ng/ml in plasma. The utility of the assay was demonstrated by determining plasma levels of I and II in five dogs administered an oral dose of 60 mg of the drug.

Animals↗