Search PubMed⌕ Search

Biomedical subjects

Y Arai

Publications and source records attributed to Y Arai.

At least 217 records · Page 12Linked to original sources

Different polysialic acid-neural cell adhesion molecule expression patterns in distinct types of mossy fiber boutons in the adult hippocampus.

Dentate granule cells continue to be generated in the adult hippocampus, and the newly generated granule cells express the highly polysialylated neural cell adhesion molecule (PSA-NCAM), which has been shown to be important in neural development and plasticity. In the present study, the PSA-NCAM expression pattern in morphologically distinct types of mossy fiber boutons in adult rats was examined by immunoelectron and confocal laser scanning microscopy. Although many unmyelinated axons within the mossy fiber bundles expressed PSA-NCAM, most of the mature type of mossy fiber boutons were negative for polysialic acid (PSA) but positive for NCAM peptides, suggesting that NCAM is less polysialylated in the mature mossy fiber boutons. On the other hand, PSA was expressed by small round varicosities, irregularly shaped boutons, and the presumptive immature type of mossy fiber boutons. The PSA-positive small boutons were found to make synaptic contacts with CA3 pyramidal cells and nonpyramidal cells. The PSA-expressing presumptive immature boutons contained fewer clear synaptic vesicles and mitochondria, and, in some instances, they were invaginated by the PSA-positive, finger-like dendritic outgrowths arising from the dendritic shafts of the pyramidal cells, which are known to develop into a mossy fiber bouton-thorny excrescence complex. These findings indicate that distinct types of the mossy fiber boutons possess different PSA expression patterns in the adult hippocampus, and they also imply that PSA expression allows the mossy fibers to have the ability to regulate the bouton formation and remodeling that accompany synapse formation at the contact sites with pyramidal cells and nonpyramidal cells.

Animals↗

Tying a molecular knot with optical tweezers.

Filamentous structures are abundant in cells. Relatively rigid filaments, such as microtubules and actin, serve as intracellular scaffolds that support movement and force, and their mechanical properties are crucial to their function in the cell. Some aspects of the behaviour of DNA, meanwhile, depend critically on its flexibility-for example, DNA-binding proteins can induce sharp bends in the helix. The mechanical characterization of such filaments has generally been conducted without controlling the filament shape, by the observation of thermal motions or of the response to external forces or flows. Controlled buckling of a microtubule has been reported, but the analysis of the buckled shape was complicated. Here we report the continuous control of the radius of curvature of a molecular strand by tying a knot in it, using optical tweezers to manipulate the strand's ends. We find that actin filaments break at the knot when the knot diameter falls below 0.4 microm. The pulling force at breakage is around 1 pN, two orders of magnitude smaller than the tensile stress of a straight filament. The flexural rigidity of the filament remained unchanged down to this diameter. We have also knotted a single DNA molecule, opening up the possibility of studying curvature-dependent interactions with associated proteins. We find that the knotted DNA is stronger than actin.

Actins↗

Hepatitis C virus structural proteins induce liver cell injury in transgenic mice.

To develop an animal model of hepatitis C virus (HCV) infection, transgenic mice carrying part of the HCV cDNA (C980) encoding HCV-core and envelope proteins under control of the mouse class I major histocompatibility complex gene (H-2K) regulatory region were produced. HCV-C980 RNA and HCV-core protein were present in livers from line H36 as determined by RNase protection assay and immunostaining, respectively. More than 40 animals from line H36 were examined histologically. Most of these H36 mice after 10 months of age developed spontaneous focal infiltration of lymphocytes, hepatocyte necrosis, degeneration, and altered foci with mitotic hepatocytes. These pathological lesions were absent in livers from the age-matched control littermates. Liver cells from these H36 mice were sensitive to damage induced by intravenous administration of an anti-Fas antibody. It is suggested that HCV-C980 proteins by themselves may be one causative agent of liver cell injury in subjects with HCV infection.

Animals↗

Treatment for empyema with bronchopleural fistulas using endobronchial occlusion coils: report of a case.

We report herein the case of a woman with bronchopleural fistulas treated with the endobronchial placement of vascular embolization coils. She was referred to our hospital to undergo lavage of a postoperative empyema. She had undergone an air plombage operation for pulmonary tuberculosis 9 years previously. However, bronchopleural fistulas occurred postoperatively and she had to continue the use of a chest drainage tube since then. Lavage of her empyema space with 5kE of OK-432 (Picibanil: Chugai) plus 100 mg minocycline was performed once every 2 weeks for 3 months, and the purulent discharge from the empyema remarkably decreased. Thereafter, the bronchopleural fistulas were occluded endobronchially by the placement of vascular embolization coils. Soon after the procedure, air leakage from the fistulas was stopped and the drainage tube was removed 2 days later. The patient remains well without any additional treatment at 20 months after this treatment. As treatment for empyema with bronchopleural fistulas, it would be worth trying to lavage the empyema space with OK-432 until it is cleaned out and to plug the fistulas by the endobronchial placement of embolization coils, before such radical operations as thoracoplasty and space-filling of the empyema are considered.

Bronchial Fistula↗

In situ right internal thoracic artery graft for revascularization of circumflex artery. Early results and long-term angiographic follow up.

In 285 patients, the right internal thoracic artery, routed through the transverse sinus, was in most cases anastomosed to the circumflex branches. In 278 cases, the left internal thoracic artery was simultaneously used for revascularization of the left anterior descending artery. Two patients died (mortality rate 0.7%). Postoperative early angiography on 278 patients revealed a high graft patency of 97.8% for the right internal thoracic artery and 96.9% for the left internal thoracic artery. A long-term follow-up study was performed on the first consecutive 115 patients who survived the operation. Seven patients died, 2 due to cardiac causes. Angiographic assessment was performed in 73 patients (67%) at an interval of 28.8 to 93.1 months (mean 58.9 months). Five right internal thoracic arteries were occluded and sledlike right internal thoracic artery grafts were present in 2 patients. Two of them had been confirmed in the previous early study to be not patent. Insufficient data was obtained in 4 patients. The perfect patency rate of the right internal thoracic artery was 89.9% (62/69). Five left internal thoracic arteries were occluded, providing a perfect patency rate of 92.3%. There was no significant difference between the success rate using the right internal thoracic artery and that resulting from using the left internal thoracic artery. We conclude that coronary revascularization using this technique provides good clinical results and excellent early and late patency of the right internal thoracic artery.

Adolescent↗

Loss of the TSC2 product tuberin in subependymal giant-cell tumors.

We investigated immunocytochemically the expression of tuberin, the TSC2 gene product, in brain resections from children with and without tuberous sclerosis, to characterize the phenotype of balloon and tumor cells, and to elucidate the relationship between tuberin and formation of subependymal giant-cell tumors. In cortical tubers, tuberin was expressed in processes and cell bodies of balloon cells, which also showed consistent vimentin and nestin immunoreactivity, but no glial fibrillary acidic protein, neurofilament, or galactocerebroside positivity by immunofluorescence confocal microscopy. The majority of balloon cells in white matter showed weaker tuberin immunoreactivity than similar cells in cortical tubers. In subependymal giant-cell tumors, there was minimal to no immunoreactivity. Why tuberin is expressed in tubers but not in subependymal giant-cell tumors is not known. If tuberin plays a role in tumor suppression, then lack of tuberin might be a marker for deletion of both alleles, leading to enhanced cellular growth in subependymal giant-cell hamartomas, eventually of sufficient size to cause clinical symptoms.

Adolescent↗

A comparison of cell phenotypes in hemimegalencephaly and tuberous sclerosis.

Hemimegalencephaly, an uncommon sporadic nonfamilial congenital dysplastic abnormality of the central nervous system, constitutes a pathological spectrum of neuronal migration disorders, but consistently includes abnormal large neurons similar to those in the cortical tubers of tuberous sclerosis. Microscopically, there are also cells with homogeneous and weakly eosinophilic cytoplasm with a single eccentric nucleus, sometimes called balloon cells (likewise prominent in tuberous sclerosis). We looked for immunohistochemical and ultrastructural differences in the large neurons and balloon cells between hemimegalencephaly and tuberous sclerosis. Microtubule-associated protein 1B and 2, phosphorylated and non-phosphorylated neurofilament and synaptophysin identify the large neurons and distinguish them from balloon cells in both entities. Balloon cells in hemimegalencephaly showed no immunoreactivity for TSC2 gene product, tuberin, and vimentin, but similar cells in tuber tissue showed consistent immunoreactivity. Balloon cells in hemimegalencephaly showed no immunoreactivity for glial fibrillary acidic protein, but some cells in tubers showed such immunoreactivity. Ultrastructurally, balloon cells in hemimegalencephaly contained very few lysosomes, microfilaments, and microtubules, but abundant lipofuscin granules. Similar cells in tubers had prominent lysosomes, more microfilaments and microtubules, and very few lipofuscin granules. The resemblance between abnormal cells in hemimegalencephaly and tuberous sclerosis is superficial; their immunohistochemistry and electron microscopic profiles show distinct differences.

Adolescent↗

Pulmonary thromboembolism after spinal instrumentation surgery.

A 57-year-old woman was hospitalized because of gait disturbance and dysuria. Close examination revealed a cauda equina tumor at the level of L2 and L3. Tumor resection was performed, with posterolateral fusion and spinal instrumentation. On the eleventh day after the surgery, she experienced dyspnea and chest pain during standing and walking exercise. Pulmonary thromboembolism was diagnosed, based on: (1) blood gas analysis findings of hypoxemia and (2) defective images in both of the upper lobes on urgent pulmonary blood flow scintigram. Her clinical status improved with urgent thrombolytic therapy (with tisokinase and urokinase) and anticoagulation therapy (with heparin and warfarin), and her life was saved. When pulmonary thromboembolism occurs, early diagnosis by pulmonary blood flow scintigram and early thrombolytic and anticoagulative therapies are necessary. Special attention should be paid to symptoms of pulmonary thromboembolism in patients after spinal surgery.

Anticoagulants↗

Murine cytomegalovirus immediate-early promoter directs astrocyte-specific expression in transgenic mice.

Murine cytomegalovirus (MCMV), which causes acute, latent, and persistent infection of the natural host, is used as an animal model of human cytomegalovirus (HCMV) infection. Transcription of MCMV immediate-early (IE) genes is required for expression of the early and late genes and is dependent on host cell transcription factors. Cell-type-specific expression activity of the MCMV IE promoter was analyzed in transgenic mice generated with the major IE (MIE) enhancer/promoter involving nucleotides -1343 to -6 (1338 bp) connected to the reporter gene lacZ. Distinct expression was observed in the brain, kidneys, stomach, and skeletal muscles. Weak expression was observed in a portion of the parenchymal cells of the salivary glands and pancreas, and expression was hardly detected in the lungs, intestine, or immune and hematopoietic organs such as the thymus, spleen, lymph nodes, and bone marrow. The spectrum of organs positive for expression was narrower than that of the HCMV MIE promoter-lacZ transgenic mice reported previously and showed a greater degree of cell-type specificity. Interestingly, astrocyte-specific expression of the transgene was observed in the brain and primary glial cultures from the transgenic mice by combination of beta-galactosidase (beta-Gal) expression and immunostaining for cell markers. However, the transgene was not expressed in neurons, oligodendroglia, microglia, or endothelial cells. Furthermore, the beta-Gal expression in glial cultures was stimulated significantly by MCMV infection or by addition of calcium ionophore. These observations indicated that expression activity of the MCMV IE promoter is strictly cell-type specific, especially astrocyte-specific in the brain. This specific pattern of activity is similar to that of natural HCMV infection in humans.

Animals↗

Antiatherogenic effect of angiotensin converting enzyme inhibitor (benazepril) and angiotensin II receptor antagonist (valsartan) in the cholesterol-fed rabbits.

The purpose of this study was to determine whether an angiotensin converting enzyme (ACE) inhibitor, benazepril, and an angiotensin receptor antagonist, valsartan, would decrease atherosclerotic severity in cholesterol-fed rabbits. Male rabbits were fed either: (a) normal rabbit chow; (b) 2% cholesterol diet; (c) 2% cholesterol diet supplemented by benazepril (3 mg/kg per day, subcutaneous injection); or (d) 2% cholesterol diet supplemented by valsartan (1 mg/kg per day, subcutaneous injection). After 12 weeks, the arteries were harvested for histomorphometry and immunohistochemistry. We observed that decreases in serum triglyceride (TG) and total cholesterol (TC) and ACE activity with benazepril-treatment were more than 60, 30, and 84%, respectively, in comparison with the cholesterol group; with valsartan-treatment, TG levels were 53% lower than in the cholesterol group, however, there was no significant difference in TC and ACE activity. The percentage of aortic surface atherosclerotic area, intimal thickness and the ratio of aortic intimal area to medial area were about 40% lower in the benazepril-treated group in comparison with those of the cholesterol group; the difference was more than 60% in the thoracic aorta. The valsartan-treated group had 23% less atherosclerotic area, less effective than benazepril treatment. The percent of PCNA-positive cells and the number of intimal proliferative cells/mm2 were significantly less in the benazepril-treated group compared with the cholesterol group (by 55 and 63%); these parameters were 35 and 17% lower, respectively, with valsartan. The ratio of proliferating macrophages to smooth muscle cells (SMCs) was 3:1 in the cholesterol group, 1:1 in the benazepril and 2:1 in the valsartan-treated group. These results indicate that benazepril could reduce atherosclerotic progression by decreasing macrophage proliferation and accumulation in the arterial wall. The mechanisms for reducing atherosclerotic progression by benazepril and valsartan may be related to reduction of TG and blockade of the angiotensin II action.

Analysis of Variance↗

Voiding function of orthotopic ileal neobladder in women.

OBJECTIVES: Although the advent of orthotopic lower urinary reconstruction in women is a major achievement in the evolution of urinary diversion, the mechanism of voiding dysfunction remains incompletely understood. We report on the voiding function of ileal neobladder in 12 female patients. METHODS: A neobladder was constructed using an ileal segment. Voiding function was evaluated in terms of voiding pattern and continence. Chain cystography was performed postoperatively to detect the existence of urethral angulation. Median follow-up was 33.2 months (range 8.4 to 77.4). RESULTS: Of the 1 2 patients, 10 (83.3%) achieved excellent daytime continence, and 6 (50%) had nighttime incontinence despite regular voiding during the night. Three patients (25%) sometimes or often performed self-catheterization because of difficulty in urinating. One patient (8.3%) was unable to void and required regular intermittent catheterization. Chain cystogram revealed urethral angulation in the 3 patients with difficulty in urinating or hypercontinence. CONCLUSIONS: An orthotopic neobladder can be constructed in women with excellent functional results. Urethral angulation appears to be one of the main mechanisms for voiding dysfunction, and further studies on the functional anatomy of the female urethra are needed to improve the voiding function of the orthotopic neobladder in women.

Aged↗

Long-term results of a randomized trial for the treatment of Stages B2 and C prostate cancer: radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities.

OBJECTIVES: To improve the treatment of locally advanced prostate cancer (Stages B2 and C), a prospective randomized trial was conducted to compare radical prostatectomy versus external beam radiotherapy with the combination of endocrine therapy in both modalities. METHODS: One hundred patients were enrolled and 95 were evaluated. Forty-six patients underwent radical prostatectomy with pelvic lymph node dissection, and 49 were treated with radiation by linear accelerator with 40 to 50 Gy to the whole pelvis and a 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiation, and continued thereafter. The living patients were asked to respond to a quality-of-life questionnaire. RESULTS: The follow-up period ranged from 6.0 to 94.4 months (median 58.5). The progression-free and cause-specific survival rates at 5 years were 90.5% and 96.6% in the surgery group and 81.2% and 84.6% in the radiation group, respectively. The surgery group had better progression-free and cause-specific survival rates (P = 0.044 and 0.024, respectively). More patients in the surgery group complained of urinary incontinence. The questionnaire revealed that quality of life was less disturbed in the radiation group. CONCLUSIONS: Radical prostatectomy combined with endocrine therapy may contribute to the survival benefit of patients with locally advanced prostate cancer. External beam radiotherapy in combination with endocrine therapy can be used in selected patients because of its low morbidity.

Adenocarcinoma↗

Complexed prostate-specific antigen and its volume indexes in the detection of prostate cancer.

OBJECTIVES: To evaluate complexed prostate-specific antigen (cPSA), cPSA density (cPSAD), and cPSA adjusted for the transition zone volume (cPSA-TZ) in comparison with the free-to-total PSA ratio (F/T PSA) and free-to-complexed PSA ratio (F/C PSA) as a means of diagnosing prostate cancer. METHODS: Transition zone volume was determined in 137 of 142 men who underwent systematic sextant biopsies and had total PSA (tPSA) values between 4.1 and 10.0 ng/mL. cPSAD and cPSA-TZ were calculated by dividing the cPSA value by the whole prostate volume and the transition zone volume, respectively. RESULTS: Of the 137 men, 23 (16.8%) had prostate cancer. cPSA predicted the biopsy outcome better than tPSA, F/T PSA, or F/C PSA, although the difference was not significant. A cutoff value of 4.1 ng/mL for cPSA provided a specificity of 42% and a sensitivity of 87%. A combination of cPSA and F/C PSA maintained a sensitivity of 83% and gave an increased specificity of 54%. In a subgroup of 65 patients with smaller prostate volumes (less than 45 mL), the diagnostic value of cPSA-TZ was remarkably increased. A cutoff value of 0.31 for cPSA-TZ provided a sensitivity of 93% and a high specificity of 72%. CONCLUSIONS: cPSA was more specific than tPSA and F/T PSA. As a component of F/C PSA, free PSA could provide additional value to cPSA. cPSA-TZ and cPSAD could be better indicators for prostate cancer than cPSA.

Aged↗

Pelvic malignant mixed mesodermal tumor of uncertain origin: a case report.

Extra-uterine, and especially extragenital, malignant mixed mesodermal tumors (MMMT) are very rare. A large intrapelvic tumor resected from a 56-year-old woman was investigated with morphological and immunohistochemical methods. A large, soft and fragile tumor was located in the pelvic space. The tumor showed high cellularity and was biphasic; it consisted of an admixture of adenocarcinoma and various kinds of sarcomas. The latter were comprised of high-grade endometrial stromal sarcoma, pleomorphic sarcoma, and chondrosarcoma. The pleomorphic sarcoma showed a storiform pattern. The periodic acid-Schiff-positive eosinophilic hyaline droplets and globules in multinucleated giant cells revealed a typical ring-like or peripheral staining for alpha-1-antitrypsin and alpha-1 antichymotrypsin. We considered this case to be pelvic MMMT of uncertain origin, heterologous type.

Combined Modality Therapy↗

Optical mapping reveals the functional organization of the trigeminal nuclei in the chick embryo.

The functional organization of the trigeminal nuclei during embryogenesis was investigated using multiple-site optical recording with a fast voltage-sensitive dye. Brainstem preparations with three classified trigeminal nerve afferents, the ophthalmic, maxillary and mandibular nerves, together with motor nerve fibers, were dissected from five- to eight-day-old chick embryos. Electrical responses evoked by trigeminal nerve stimulations were optically recorded simultaneously from many loci of the stained preparations. We identified three response areas related to the trigeminal nerve: area I, located cephalic to the level of the trigeminal ganglion; area II, located caudal to the level of the trigeminal ganglion; and area III, located at the level of the trigeminal root. The neural responses in areas I and II were evoked by ophthalmic, maxillary or mandibular nerve stimulation, while the responses in area III were detected when the stimulation was applied to the trigeminal motor nerve. In comparison with the morphology indicated by DiI labeling, the results suggest that areas I, II and III correspond to the principal sensory nucleus of the trigeminal nerve, the spinal sensory nucleus of the trigeminal nerve and the trigeminal motor nucleus, respectively. We identified two components of the optical response: a fast and a slow signal. In five-day-old preparations, fast spike-like signals related to action potentials were recorded from the three response areas. In six-day-old preparations, slow optical signals which reflect glutamate-mediated excitatory postsynaptic potentials were detected from area II only when the ophthalmic nerve was stimulated: no slow signal was evoked by maxillary or mandibular nerve stimulation. In seven- and eight-day-old preparations, slow signals were detected from both areas I and II with every nerve stimulation. These results suggest that synaptic function is first generated in the spinal trigeminal nucleus by the six-day embryonic stage, and the developmental organization of synaptic function is not the same in the three trigeminal nerves or in the two sensory nuclei. Contour line maps of the signal amplitude revealed that the size and the area of the neural responses within the trigeminal nuclei changed dramatically with development. We compared the spatial distribution and temporal dynamics of the optical signals between the ophthalmic, maxillary and mandibular nerve stimulations, and we found that somatotopic organization is less clear in a rostrocaudal/mediolateral X-Y plane, although the areas of the maxillary and mandibular nerves appeared to separate in the lateral direction.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Effect of icatibant, a bradykinin B2 receptor antagonist, on the development of experimental ulcerative colitis in mice.

Dextran sulfate sodium-induced colitis in mice has been recognized as a model for human ulcerative colitis. Using this model, we carried out a study on the preventive effect of Icatibant, a bradykinin B2 receptor antagonist previously called HOE 140, on the development of colitis. Subcutaneous administration of Icatibant (0.3 or 1.5 mg/kg) significantly suppressed shortening of the large intestine and worsening of the general health. Oral administration of Icatibant (50 mg/kg) significantly suppressed shortening of the large intestine, the onset of diarrhea, and worsening of the general health. In addition, the oral treatment significantly inhibited the development of colitis that was observed histopathologically. These results indicate a role of BK in the development of dextran sulfate sodium-induced colitis in mice, and suggest that BK could be important in human ulcerative colitis.

Administration, Oral↗