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Biomedical subjects

S Hirai

Publications and source records attributed to S Hirai.

At least 145 records · Page 8Linked to original sources

[Clinical studies on the prognostic factors in prostate cancer].

To evaluate the prognostic factors and the outcome of treatment, a retrospective study was done on 141 patients with prostate cancer who were newly diagnosed at Kitano Hospital between January 1985 and November 1996. In recent years, the number of patients and the ratio of low stage cancer have increased. The overall 5-year crude survival rate was 49.9%. The 5-year crude survival rate for clinical stage A, B, C and D was 67%, 70%, 62% and 30% respectively. The overall 5-year disease-specific survival rate was 65.6%. The 5-year disease-specific survival rate for clinical stage A, B, C and D was 100%, 89%, 72% and 42%, respectively. By univariate analysis, clinical stage, Gleason score, prostate specific antigen (PSA) level, and patient age were prognostic factors for disease-specific survival of prostate cancer. According to Cox's regression analysis by the stepwise forward regression method, clinical stage and Gleason score were selected as more valuable prognostic factors than PSA level, patient age, comorbidity, and initial treatment. In Gleason score 2 to 8, the prognosis became significantly worse as clinical stage advanced, but in Gleason score 9 and 10 the prognosis was poor regardless of clinical stage.

Aged↗

[Myopathology of the intrinsic laryngeal muscles in neurodegenerative diseases, with reference to the mechanism of vocal cord paralysis].

To investigate the mechanism of the vocal cord abductor paralysis (VCAP) in the neurodegenerative diseases, the intrinsic laryngeal muscles (the crycothyroid, the interarytenoid, and the posterior crycoarytenoid muscles) from 41 autopsied cases were histologically examined: 10 cases of amyotrophic lateral sclerosis (ALS), 10 of Parkinson's disease (PD), 9 of multiple system atrophy (MSA), 4 of Machado-Joseph disease (MJD), 4 of progressive supranuclear palsy (PSP), 1 of familial amyloidotic polyneuropathy (FAP), and 3 of cerebrovascular diseases as a control. According to the distribution of the neurogenic changes among above-described three intrinsic laryngeal muscles, three forms were raised: 1. The totally paralytic form showing that all the three muscles developed neurogenic atrophy. This form includes ALS, MJD, and FAP. 2. The posterior muscle-paralytic form showing that only the posterior crycoarytenoid muscle was selectively involved. This form includes MSA. 3. The nonparalytic form showing no morphological abnormalities in any of the intrinsic laryngeal muscles. This type includes PD and PSP. In this nonparalytic form, supranuclear mechanism such as pyramidal or extrapyramidal tract involvement may cause VCAP through the increased laryngeal muscles tone. Considering that VCAP can be seen in any of the above-described forms, our results indicate that the mechanism of VCAP is different among the neurological disorders.

Atrophy↗

Prominent sensory and autonomic disturbances in familial amyotrophic lateral sclerosis with a Gly93Ser mutation in the SOD1 gene.

A missense mutation (Gly93-->Ser) was identified in exon 4 of the Cu/Zn superoxide dismutase (SOD1) gene of a 48-year-old Japanese man with familial amyotrophic lateral sclerosis (FALS). The SOD1 activities in the fibroblasts and in a lysate of erythrocytes of the patient did not differ from those of healthy controls. The clinical characteristics of the patient were fairly slow progression of the illness, prominent sensory impairment, urinary disturbance and blood pressure fluctuation due to sympathetic hyperactivity. The severe sensory and autonomic disturbances, association of which with FALS has not been previously reported, may represent specific clinical features associated with the Gly93Ser mutation or may indicate the variability of clinical findings even in patients with the same mutation.

Amyotrophic Lateral Sclerosis↗

Involvement of protein kinase C in the activation of extracellular signal-regulated kinase 1/2 by UVC irradiation.

UVC irradiation activates mitogen-activated protein kinases (MAPKs), including ERK, JNK, and P38. This study examined the role of protein kinase C (PKC) in the regulation of UVC-stimulated MAPKs activation. Either the depletion of PKC by prolonged treatment of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) or the inhibition of PKC by a selective PKC inhibitor, UCN-01-ME, attenuated UVC-activation of ERK1/2, keeping the activation of JNK1/2 intact. However, K252a, a non-selective PKC inhibitor, inhibited the activation of both ERK1/2 and JNK1/2 by UVC. In three isoforms of PKC (alpha, delta, epsilon) examined, PKC epsilon shows the most evident translocation, a temporal association with cell membrane, upon the UVC irradiation of NIH 3T3 cells. These results suggest that PKC is acting in the UVC-dependent activation of ERK1/2, and PKC epsilon is one of the PKC isozymes playing such a role.

3T3 Cells↗

Lysosomal generation of amyloid beta protein species in transgenic mice.

Soluble amyloid beta protein (A beta)1-40 and highly amyloidogenic A beta 1-42/43 were immunocytochemically labeled in lysosomes of acinar cells and macrophages in the pancreas of transgenic mice systemically expressing a C-terminal fragment of the A beta precursor. A beta 1-42/43 and long A beta species extending their C-termini were detected in the detergent-insoluble fraction. Immunoreactivity of cathepsin D was markedly increased in lysosomes filled with A beta fibrils. These findings indicated that A beta 1-40, A beta 1-42, A beta 1-43 and longer A beta species were generated in the lysosomes of the transgenic pancreas, and suggested that the activation of cathepsin D, a candidate gamma-secretase, leads to acceleration of A beta amyloid formation.

Amyloid beta-Protein Precursor↗

Amyloid beta protein 42(43) in cerebrospinal fluid of patients with Alzheimer's disease.

To investigate the pathomechanism of amyloid beta protein (A beta) deposition in brains with Alzheimer's disease (AD), cerebrospinal fluid (CSF) levels of A beta species (CSF-A beta) with different carboxy termini, i.e. A betaX-40 and A betaX-42(43) as well as A beta1-40 and A beta1-42(43), were measured in patients with AD and age-matched controls without dementia (CTR) using sandwich enzyme-linked immunosorbent assays (ELISAs). The present study revealed that both CSF-A betaX-42(43) and A beta1-42(43) levels were significantly lower in the AD patients (P<0.005) than in the CTR group, whereas neither CSF-A betaX-40 nor CSF-A beta1-40 levels showed any differences between the two groups. In addition, although there was no difference between the ratios of A betaX-40 to A beta1-40 in the AD and CTR groups, the ratios of A betaX-42(43) to A beta1-42(43) were increased in the AD group compared with those in the CTR group (P<0.05). Therefore, it can be assumed that the ratios of amino terminal truncations and/or modifications of CSF-A beta42(43) with carboxy termini ending at residue 42(43) were more increased in the AD group than in the CTR group. Increased adsorption of A beta42(43) to A beta deposition in AD brains, decreased secretion of A beta42(43) to CSF and/or increased clearance of A beta42(43) from CSF might explain the diminished levels of A beta42(43) in the CSF of AD patients. In addition, CSF-A beta42(43) could reflect increased amino terminal truncations and/or modifications of A beta42(43) in AD brains.

Aged↗

YSK1, a novel mammalian protein kinase structurally related to Ste20 and SPS1, but is not involved in the known MAPK pathways.

To clarify the upstream regulatory mechanism of mitogen-activated protein kinase (MAPK), we performed the reverse transcriptase-based polymerase chain reaction (RT-PCR) with degenerate primers synthesized based on sequences conserved among the kinase domains of yeast MAPK kinase kinases (MAPKKKs), Stell, Bck1, and Byr2. We isolated several mammalian cDNA fragments that encode kinase subdomains sharing significant sequence homology with yeast MAPKKKs. Subsequent screening of a HeLa cell cDNA library using one of these cDNA fragments as a probe resulted in the isolation of a full-length cDNA that encodes a novel protein kinase. The catalytic domain sequence of this gene product is closely related to those of budding yeast Sps1 and Ste20 protein kinases. Thus, we call this protein YSK1 (Yeast Sps1/Ste20-related Kinase 1). The transcript of YSK1 was detected in a wide range of tissues and cells. Immunoprecipitated YSK1 shows protein kinase activity. Although YSK1 is significantly similar in its kinase domain to kinases of the yeast and mammalian MAPK pathways, the overexpression of YSK1 did not lead to the activation of the ERK (extracellular signal-regulated kinase) pathway, JNK (c-Jun NH2-terminal kinase)/SAPK (stress-activated protein kinase) pathway, or p38/Mpk2 pathway. These results suggest that YSK1 may be involved in the regulation of a novel intracellular signaling pathway.

Amino Acid Sequence↗

A domain containing the Cdc42/Rac interactive binding (CRIB) region of p65PAK inhibits transcriptional activation and cell transformation mediated by the Ras-Rac pathway.

The molecular bases of the versatile functions of Rho-like GTPases are still unknown. Using luciferase assays with rat 3Y1 cells, we found that Rac1 is integrated downstream of Ras in the TRE (TPA response element) activation pathway. Coexpression of a mutant of p65PAK, PAK/RD, lacking the kinase domain but containing the Cdc42/Rac interactive binding (CRIB) region, suppressed the TRE activation and cell transformation caused by constitutively activated forms of Ras (RasV12) and Rac1 (Rac1V12). PAK/RD is a good tool to investigate the signaling pathways in which Rac and Cdc42 are involved.

Amino Acid Sequence↗

Orthotopic transplantation of a partial hepatic autograft in dogs.

The purpose of this study was to investigate the availability of an orthotopic transplantation of partial hepatic autograft in dogs as a means of surgical training. Male mongrel dogs weighting 10-15 kg were used. The left lobe of the liver was harvested while preserving the left branches of the portal vein, hepatic artery and bile duct, and the left hepatic vein. The remnant liver was removed while preserving the inferior vena cava using a veno-venous bypass. Orthotopic transplantation of the autograft was performed while anastomosing the left hepatic vein to the inferior vena cava, portal and arterial reconstruction, and external biliary drainage. Thirteen out of 29 dogs survived more than 48 h after transplantation. However, 6 out of 13 dogs were sacrificed after developing bile peritonitis due to a dislodgement of the biliary catheter, and only two dogs were able to survive for 7 days after transplantation. The arterial ketone body ratio recovered to 1.0 within 1 h after reperfusion, and the ratio of the dogs that survived for more than 48 h remained above 1.0 until sacrifice. Orthotopic transplantation of a partial hepatic autograft is a useful and simple procedure to train surgeons for partial liver transplantation.

Animals↗

Multiple early esophageal cancers arising from Barrett's esophagus, and a review of cases of early adenocarcinoma in Barrett's esophagus in Japan.

A case of early esophageal adenocarcinoma arising in Barrett's esophagus is reported. Many cases of Barrett's esophagus, which is considered a premalignant condition, have been reported in Western countries, but few cases have been reported in Japan. The patient, a 53-year-old man with nausea and vomiting, was a drinker (four glasses wine/day for about 30 years), but did not smoke. He had had a hiatal hernia of the esophagus. Since endoscopic biopsies demonstrated an early adenocarcinoma in Barrett's esophagus, subtotal esophagectomy was performed. In the resected esophageal material, Barrett's esophagus was seen to extend for 12 cm. In addition to the cancer detected preoperatively as a 0-IIc lesion (1.5 cm in diameter), a 0-IIb lesion (1.5 cm in diameter) was also detected in the postoperative survey. Both lesions were well differentiated adenocarcinoma that had invaded only into the lamina propria mucosa. The 23 cases of early adenocarcinoma in Barrett's esophagus that have been reported in Japan were reviewed, and it was learned that the present case is the second of multiple early cancer arising in Barrett's esophagus so far reported in Japan.

Adenocarcinoma↗

Ultrastructural characterization of the tau-immunoreactive tubules in the oligodendroglial perikarya and their inner loop processes in progressive supranuclear palsy.

Coiled bodies and interfascicular threads are conspicuous white matter abnormalities of brains of patients with progressive supranuclear palsy (PSP). Both structures are argyrophilic and immunoreactive for the microtubule-binding protein tau. This report concerns the ultrastructural localization of interfascicular threads and their relationship to coiled bodies in five PSP patients. We showed for the first time that abnormal tubules with a 13- to 15-nm diameter and fuzzy outer contours were the common structures of coiled bodies in the oligodendroglial perikarya and of interfascicular threads. Moreover, the tubules were immunolabeled by anti-tau antibodies. The abnormal tau-positive tubules of interfascicular threads were located in the inner loop of the myelin sheath. Our study further indicated that the thread-like structures in the white matter comprised, at least in part, oligodendroglial processes, and that they were also present in gray matter. We consider that the formation of coiled bodies in the perikarya and of interfascicular threads represents a common cytoskeletal abnormality of the oligodendroglia of PSP patients. Moreover, even though the white matter alterations of PSP resemble those of corticobasal degeneration, there are certain ultrastructural differences in the abnormal oligodendroglial tubules of the two diseases.

Aged↗

Efficacy of a simple left atrial procedure for chronic atrial fibrillation in mitral valve operations.

BACKGROUND: We have devised a simple surgical procedure to be performed on the posterior wall of the left atrium for the treatment of chronic atrial fibrillation (AF) associated with mitral valve disease. The effectiveness of this procedure for serial mitral valve operations was then evaluated. We postulated that chronic AF associated with mitral valve disease could be attributable to a distended left atrium. The refractory period of the distended left atrium was significantly shorter in the left posterior atrial wall, especially at the base of the left atrial appendage and at the orifice of the left posterior pulmonary vein. We hypothesized that the left posterior atrial wall with its shorter fibrillatory cycle length would act as a driver for maintaining the AF, and therefore, surgical ablation of this critical area in the left atrium could terminate the chronic AF. METHODS: The surgical patients were divided into two groups. In group 1 (control group), 15 patients with chronic AF were operated on by the mitral valve procedure only. In group 2, 36 patients underwent this procedure in combination with a concomitant mitral valve operation. The disappearance rate of the AF was estimated by electrocardiography, and atrial function was estimated by transthoracic and transesophageal echocardiography. RESULTS: The chronic AF had been reduced significantly or eliminated at discharge in 4 of 15 patients (26.7%) in the group 1, versus 31 of 36 patients (86%) in group 2 (p < 0.05). In group 2, 29 of the 31 patients (94%) whose AF had disappeared recovered the atrial kick of their right atrium, and 21 patients (22/31; 71%) recovered the atrial kick of their left atrium. CONCLUSIONS: Surgical ablation of the posterior wall of the left atrium was effective in the treatment of chronic AF associated with mitral valve disease. This simple procedure could restore a sinus rhythm and also recovered atrial systolic function. We conclude that the left atrium may act as a driver for sustaining AF in mitral valve disease.

Aged↗

Right atrial separation for chronic atrial fibrillation with atrial septal defects.

A right atrial separation procedure was performed for the ablation of atrial fibrillation during the concomitant repair of an atrial septal defect. This procedure consisted of a Y-shaped incision in the right atrium, followed by cryoablation of the tricuspid annulus and the atrial septum without any procedures performed on the left atrium. This is a simple and effective method for the elimination of chronic atrial fibrillation associated with atrial septal defects in adults.

Atrial Fibrillation↗

Flow velocity of central retinal artery and retrobulbar vessels during cardiovascular operations.

OBJECTIVE: Both blood flow monitoring and pressure monitoring are necessary to avoid inadequate cerebral perfusion during cardiovascular operations. Inasmuch as transcranial Doppler ultrasonography does not provide a consistently good signal, especially during cardiopulmonary bypass, we examined the blood flow through the central retinal artery, which has proved to reflect an obstruction of the carotid artery. METHOD: Twenty-eight consecutive cases were examined with a 5 or 7.5 MHz conventional echocardiographic probe. Correlation between the maximal velocity at the central retinal artery and systolic blood pressure was examined. The blood flow of the central retinal artery and retrobulbar vessels was examined during selective or retrograde cerebral perfusion or intraaortic balloon pumping. RESULTS: Blood flow could be clearly visualized but disappeared below a certain pressure in every case. With data from 478 measuring points, systolic blood pressure correlated with maximal velocity (r = 0.6902, p < 0.0001). The blood pressure-axis intercept, known as "critical closing pressure," was 35.8 +/- 14.8 mm Hg, varying among individuals and bilateral eyes. Pulsatility index increased after cardiopulmonary bypass (1.095 +/- 0.245 to 1.525 +/- 0.268, p < 0.0001). Patency of the circle of Willis was confirmed by the blood flow during anastomosis of the ipsilateral artery. During retrograde cerebral perfusion, blood flow was detectable at the retrobulbar vessels. During intraaortic balloon pumping, the central retinal artery flow was augmented on inflation of the balloon. CONCLUSION: Orbital vessel monitoring provides the critical closing pressure of the central retinal artery and confirms patency of the circle of Willis. The eye can be "an acoustic window" into intracranial blood flow during cardiovascular surgery.

Aged↗

Pulsed intravenous methylprednisolone therapy for inflammatory myopathies: evaluation of the effect by comparing two consecutive biopsies from the same muscle.

To examine the effect of pulsed intravenous methylprednisolone (IVMP) on polymositis (PM) and dermatomyositis (DM), two biopsies were taken from the same muscle before and after IVMP in one case each of PM and DM. After IVMP, numerous muscle fibers were seen undergoing regeneration. Among all subsets of infiltrating cells that decreased in number, macrophages in the perivascular area decreased markedly. Also conspicuous was decrease of CD8+ cells in the endomysium in PM and that of B-cells in the perivascular area in DM. Among infiltrating cells, frequency of those which expressed the signal transducers and activators of transcription 1 (STAT-1) fell considerably, but remained still abnormally high. Regions on the endothelial cells of blood vessels that expressed MHC antigens and intercellular adhesion molecules 1 (ICAM-1) also decreased but remained more widespread than normal. These results agreed with the favorable clinical effect of IVMP, but showed that many of the immunological parameters remained abnormal.

Adult↗