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Biomedical subjects

T Manabe

Publications and source records attributed to T Manabe.

At least 37 records · Page 2Linked to original sources
PubMed2000

Combination of electrophoretic techniques for comprehensive analysis of complex protein systems.

Analysis of proteins in complex mixtures such as cell lysates is presently performed by two-dimensional polyacrylamide gel electrophoresis under denaturing conditions (denaturing 2-D PAGE) followed by extraction of proteins from gel pieces and structural analysis of the proteins. This type of protein analysis is contributing to the correlation of information stored in DNA sequences with the structure of the product polypeptides. However, denaturing 2-D PAGE has its own limitations and it is necessary to develop various methods of protein analysis to reconstruct the total structure and function of proteins in complex systems. This review article summarizes the work in our laboratory to explore proteins in human plasma combining various electrophoretic techniques: nondenaturing and denaturing 2-D PAGE, capillary electrophoresis, and agarose gel isoelectric focusing.

Animals↗
PubMed2000

Hypersegmentation of inflammatory cells in Langerhans cell granulomatosis.

Langerhans cell granulomatosis (LCG) is characterized by a mixture of Langerhans cells and eosinophils in varying proportions. The characteristic morphology of Langerhans cells have already been described in many articles, but little attention has been paid to inflammatory cells. We examined six cases of Langerhans cell granulomatosis, which had originally been diagnosed as eosinophilic granuloma. Inflammatory cells present in LCG showed hypersegmentation. Twenty percent to 70% of eosinophils had three or more segmented nuclei, and 10-25% of neutrophils had five or more segmented nuclei. Such findings have never been described, and we believe hypersegmentation to be a feature of LCG. Furthermore, we emphasize that eosinophils in LCG mimic neutrophils in ethanol-fixed preparations, and thus may be a pitfall in making a diagnosis in cytology and intraoperative consultation.

Adult↗
PubMed2000

Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses and modifies behavioral responses.

Cadherins organize symmetrical junctions between the pre- and postsynaptic membranes in central synapses. One of them, cadherin-11 (cad11), is expressed in the limbic system of the brain, most strongly in the hippocampus. Immunohistochemical studies of the hippocampus showed that cad11 proteins were densely distributed in its synaptic neuropil zones; in cultured hippocampal neurons, their distribution often overlapped with that of synaptophysin, and also occasionally with that of GluR1 at spines. To assess the role of cad11 in synaptic formation and/or function, we analyzed brains of cad11-deficient mice. In these mice, long-term potentiation (LTP) in the CA1 region of the hippocampus was, unexpectedly, enhanced; and the level of LTP saturation was increased. In behavioral tests, the mutant mice showed reduced fear- or anxiety-related responses. These results suggest that the cad11-mediated junctions may modulate synaptic efficacy, confining its dynamic changes to a limited range, or these junctions are required for normal development of synaptic organization in the hippocampus.

Animals↗
PubMed2000

Long-term outcome for right heart function after biventricular repair of pulmonary atresia and intact ventricular septum.

OBJECTIVES: The right heart function of the patients with pulmonary atresia and intact ventricular septum was assessed periodically during the process of staged biventricular repair, and the implications for its long-term outcome were analyzed. SUBJECTS AND METHODS: During the period from 1971 to 1990, 21 neonates or infants with pulmonary atresia and intact ventricular septum had undergone initial palliative surgery. There were seven early postoperative deaths and one late death. Of the 13 survivors, 10 patients underwent subsequent biventricular repair and form the basis of this study. Their clinical records of roentgenography, electrocardiography, and catheterization studies at each staged period were reviewed retrospectively. RESULTS: Arrhythmia occurred late in 2 patients, one of whom died by arrhythmia at 11 years after definitive surgical repair. Therefore the actuarial survival rate was 85.7% at 14 years. The catheterization study after the definitive biventricular repair revealed a significant fall in the right heart pressure (p = 0.0005) and significant improvement in the right ventricular ejection fraction (p = 0.0004). In angiocardiography, dilatation of the right atrium was noted in all patients and was more marked in those who developed arrhythmia in conjunction with rapid growth of the right ventricle. Moreover, the serial repeated electrocardiography disclosed progressive and significant prolongation of both PQ interval (p = 0.003) and QRS duration (p = 0.021). CONCLUSIONS: Although biventricular repair for pulmonary atresia and intact ventricular septum proved to attain a satisfactory long-term result, it failed to resolve right heart dysfunction. Postoperative arrhythmia was prone to precipitate progressive dilatation of the right atrium.

Atrial Function, Right↗
PubMed2000

Genetic linkage analysis of X-ray hypersensitivity in the LEC mutant rat.

The LEC rat has been reported to exhibit X-ray hypersensitivity and deficiency in DNA double-strand break (DSB) repair. The present study was performed to map the locus responsible for this phenotype, the xhs (X-ray hypersensitivity), as the first step in identifying the responsible gene. Analysis of the progeny of (BN x LEC)F(1) x LEC backcrosses indicated that the X-ray hypersensitive phenotype was controlled by multiple genetic loci in contrast to the results reported previously. Quantitative trait loci (QTL) linkage analysis revealed two responsible loci located on Chromosomes (Chr) 4 and 1. QTL on Chr 4 exhibited very strong linkage to the X-ray hypersensitive phenotype, while QTL on Chr 1 showed weak linkage. The Rad52 locus, mutation of which results in hypersensitivity to ionizing radiation and impairment of DNA DSB repair in yeast, was reported to be located on the synteneic regions of mouse Chr 6 and human Chr 12. However, mapping of the rat Rad52 locus indicated that it was located 23 cM distal to the QTL on Chr 4. Furthermore, none of the radio-sensitivity-related loci mapped previously in the rat chromosome were identical to the QTL on Chrs 4 and 1 in the LEC rat. Thus, it seems that X-ray hypersensitivity in the LEC rat is caused by mutation(s) in as-yet-undefined genes.

Animals↗
PubMed2000

Interstitial pneumonia in Hermansky-Pudlak syndrome: significance of florid foamy swelling/degeneration (giant lamellar body degeneration) of type-2 pneumocytes.

Although usual interstitial pneumonia (UIP)-like IP has been known as the most serious complication of Hermansky-Pudlak syndrome (HPS), its pathologic features and pathogenesis are poorly understood. We investigated biopsied and autopsied lung tissues from five patients who died of UIP-like IP associated with HPS (HPSIP). The salient histopathologic features of HPSIP observed were: (1) alveolar septa displaying florid proliferation of type-2 pneumocytes (2PCs) with characteristic foamy swelling/degeneration; (2) patchy fibrosis with lymphocytic and histiocytic infiltration centered around respiratory bronchioles, occasionally showing constrictive bronchiolitis; and (3) honeycomb change without predilection for the lower lobes or subpleural area. Those peculiar 2PCs were histochemically characterized by the over accumulation of phospholipid, immunohistochemically by a weak positivity for surfactant protein, and ultrastructurally by the presence of numerous giant lamellar bodies that compressed the nucleus with occasional cytoplasmic disruption, together suggesting a form of cellular degeneration with an over accumulation of surfactant (giant lamellar body degeneration). The present study strongly indicates that there is a basic defect in the formation/secretion process of surfactant by the 2PCs in HPS, which may well be the triggering factor for the HPSIP development. Other factors, such as macrophage dysfunction, may be working synergistically for further acceleration of the inflammatory process.

Adult↗
PubMed2000

Ruptured sinus of a Valsalva aneurysm associated with autosomal-dominant polycystic kidney disease in an elderly patient: report of a case.

We report herein the case of a 71-year-old woman with autosomal-dominant polycystic kidney disease (ADPKD), who was referred to our hospital for investigation of facial edema. Echocardiography demonstrated a large aneurysm arising from the non-coronary sinus of Valsalva, with a left to right shunt and jets of blood passing from the aneurysm toward the septal leaflet of the tricuspid valve. Surgical treatment was successfully carried out by resecting the aneurysmal wall and performing a patch closure of the orifice. It is well known that ADPKD predisposes patients to cardiovascular disease, and this case report serves to demonstrate that when a patient with ADPKD presents with progressive heart failure, the possibility of a ruptured sinus of a Valsalva aneurysm must be considered.

Aged↗
PubMed2000

Role of nociceptin systems in learning and memory.

This article summarizes our recent finding that the nociceptin system is involved in the regulation of learning and memory. The nociceptin-knockout mice show greater learning ability in the water maze task, an enhanced latent learning in the water finding task, better memory in the passive avoidance task, and further, larger long-term potentiation in the hippocampal CA1 region than wild-type mice. Nociceptin itself induces an impairment of passive avoidance task in wild-type mice, which is reversed by naloxone benzoylhydrazone (NalBzoH). Thus, the nociceptin system seems to play negative roles in learning and memory, and NalBzoH may act as a potent antagonist for the nociceptin receptor.

Animals↗
PubMed2000

Differential expression and phosphorylation of particular fos family members by kainate in nuclear and cytosolic fractions of murine hippocampus.

An i.p. injection of kainate resulted in severe losses of neuronal cells stained by Cresyl Violet in the CA1 and CA3 pyramidal layers of the murine hippocampus within two weeks, without affecting those in the dentate granule layer up to six weeks. Immunohistochemical analysis revealed marked and predominant expression of Fos family members, including c-Fos, Fos-B and Fra-2 proteins, in the dentate granule layer of the hippocampus, but not in the pyramidal layers, 2-18h after administration. Immunoblotting experiments showed that kainate induced more potent expression of c-Fos protein in nuclear fractions obtained 2h after injection than those obtained 18h later, with similar expression between cytosolic fractions obtained 2 and 18h after administration. Both Fos-B and Fra-2 proteins were more potently expressed in nuclear and cytosolic fractions 18h after administration than 2h when determined on immunoblotting analysis. Two-dimensional electrophoresis revealed expression of several proteins immunoreactive to the anti-c-Fos antibody with different isoelectric points in response to kainate in nuclear and cytosolic fractions of the hippocampus for 2-18h after a single injection. Immunoprecipitation analysis using the anti-c-Fos antibody showed phosphorylation of c-Fos protein on serine residues in hippocampal nuclear fractions 2h after administration, with additional phosphorylation on tyrosine residues 18h later. Prior treatment of the protein synthesis inhibitor cycloheximide prevented the expression of immunoreactivities to the anti-c-Fos antibody detected on two-dimensional electrophoresis in hippocampal nuclear fractions obtained 2h after administration.These results suggest that in vivo kainate signals may lead to persistent expression of the transcription factor activator protein-1 that consists of different Fos family members, as well as of c-Fos protein phosphorylated on serine and/or tyrosine residues, at an early stage after administration. Such signal consolidation processes could play a role in mechanisms associated with neuronal survival after kainate in the dentate granular layer of murine hippocampus.

Animals↗
PubMed2000

Teratocarcinosarcoma of the nasal cavity. Report of a case showing favorable prognosis.

We report a very rare case of teratocarcinosarcoma of the nasal cavity showing a favorable prognosis. The patient was a 66-year-old man with a mass completely obstructing the right nasal cavity. Subsequently, extirpation of the mass and Denker-Watsuji operation were performed, and the patient was treated with a combination of radiation therapy and chemotherapy. Neither recurrence nor distant metastasis was observed during follow-up lasting 30 months. Histologic examination of the resected mass revealed several tissue elements including columnar and squamous epithelia with atypia, smooth muscle cells with rare mitotic activity, and neuroectodermal tissue. The glandular epithelium and smooth muscle cells were reminiscent of a primitive intestinal organoid structure, suggestive of teratomatous tumorigenesis. Our case and a review of the literature indicate that the absence of invasiveness to the stroma or surrounding tissue is closely related to a favorable prognosis.

Aged↗
PubMed2000

Immunohistochemical analysis of Ki-67, p53, p21, and p27 in benign and malignant apocrine lesions of the breast: its correlation to histologic findings in 43 cases.

We examined Ki-67, p53, p21, and p27 immunolocalization in 43 cases of apocrine lesions of the breast and correlated these findings with histologic parameters to understand their biologic significance. Twenty cases were benign, 1 case was borderline, and 22 cases were diagnosed as malignant, including 9 intraductal and 13 invasive apocrine carcinomas. Both the ratio of Ki-67-positive cases (17 of 21 [88.9%] versus 1 of 19 [5.3%]; P < .001) and the Ki-67 labeling index of positive cases examined (15.0% versus 2.7%; P < .005) were significantly higher in malignant than in benign apocrine lesions. None of the benign or borderline cases was immunohistochemically positive for p53, but 15 of 22 malignant cases (68.2%) demonstrated p53 (P < .001). In addition, the ratio of p53-positive cases was significantly higher in high nuclear grade cases (11 of 13 [84.6%]) than in intermediate nuclear grade cases (4 of 9 [44.4%]; P < .05). P53 immunoreactivity was also positively correlated with the nuclear grade of carcinoma cases examined in this study. Neither p21 nor p27 demonstrated any correlation with histologic parameters or findings of the apocrine lesions. Results of these studies suggest that Ki-67 and p53 may be good markers for differentiation between benign and malignant breast apocrine lesions.

Apocrine Glands↗
PubMed2000

Genetic structure of Camellia japonica L. in an old-growth evergreen forest, Tsushima, Japan.

The spatial genetic structure of Camellia japonica was investigated, using microsatellite markers, in a 4-ha permanent plot within an old-growth forest. Spatial distribution of individuals was also assessed to obtain an insight into spatial relationships between individuals and alleles. Morisita's index of dispersion showed that 518 C. japonica individuals in the plot were clumped, and Moran's I spatial autocorrelation coefficient revealed weak genetic structure, indicating a low level of allele clustering. Average I correlograms showed that there was stronger genetic structure over short-distance classes. The clumped distribution of individuals and the positive autocorrelation over short-distance classes may result from the limited seed dispersal and microsite heterogeneity of the stand, while the genetic structure may be weakened by overlapping seed shadow and extensive pollen flow, mediated by animal vectors, and the high outcrossing rate found in C. japonica.

Ericales↗