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H Kondo

Publications and source records attributed to H Kondo.

At least 163 records · Page 9Linked to original sources
PubMed2000

Structure of the AAA ATPase p97.

p97, an abundant hexameric ATPase of the AAA family, is involved in homotypic membrane fusion. It is thought to disassemble SNARE complexes formed during the process of membrane fusion. Here, we report two structures: a crystal structure of the N-terminal and D1 ATPase domains of murine p97 at 2.9 A resolution, and a cryoelectron microscopy structure of full-length rat p97 at 18 A resolution. Together, these structures show that the D1 and D2 hexamers pack in a tail-to-tail arrangement, and that the N domain is flexible. A comparison with NSF D2 (ATP complex) reveals possible conformational changes induced by ATP hydrolysis. Given the D1 and D2 packing arrangement, we propose a ratchet mechanism for p97 during its ATP hydrolysis cycle.

Adenosine Diphosphate↗
PubMed2000

A facile synthetic approach to L- and P-selectin blockers via copolymerization of vinyl monomers constructing the key carbohydrate modules of sialyl LewisX mimics.

A highly practical synthetic approach is described for artificial L- and P-selectin blockers. The synthesis involves radical bi- and terpolymerizations of p-(N-acrylamido)phenyl 3- or/and 6-sulfo-beta-D-galactoside with allyl alpha-L-fucoside in the presence of acrylamide. Each of the two glycosyl monomers constructs a key carbohydrate module responsible for selectins/sulfated sialyl LewisX (sLeX) bindings. Whereas an acrylamide copolymer carrying 3-sulfo-galactoside showed no activity for any selectins, the fucosylated terpolymer showed a potent activity to block both of P- and L-selectins/sLeX binding at a concentration of a few micrograms per milliliter. The enhanced activity is apparently ascribed to the cooperative binding effects of the fucoside and the 3-sulfo-galactoside residues.

Carbohydrate Sequence↗
PubMed2000

Classical protein kinase C and its hypoxic stimulus-induced translocation in the cat and rat carotid body.

The presence, subcellular distribution, species specificity and possible hypoxic stimulus-induced translocation of classical protein kinase C (cPKC) isozymes were examined in the carotid body. Carotid bodies were dissected from cats exposed in vivo to normoxic or acute hypoxic conditions and from normoxic rats. For immunohistochemistry isoform-specific monoclonal antisera to PKCalpha, PKCbetaI, PKCbetaII and PKCgamma were used. The immunoreactivity was visualized by fluorescein isothiocyanate (FITC) labelling. FITC/Texas red double-labelled specimens for the cPKC isozymes/tyrosine hydroxylase were used to demonstrate the chemoreceptor cell localization of cPKC isozymes. The immunofluorescence was detected using laser scanning confocal image technology. The results showed expression of the PKCalpha and PKCgamma but not PKCbeta isoforms in the cytoplasm of carotid body chemoreceptor cells. The double labelling provided evidence for the chemoreceptor cell localization of the cPKC isoforms detected. The immunostaining was most intense in the periphery of the perikarya, the nuclear envelope and, occasionally, the nucleoplasm. No major differences were found in the immunolocalization of PKCalpha and PKCgamma under normoxic and hypoxic conditions or between species. However, the immunoreactivity tended to accumulate more in the peripheral cytoplasm and away from the nucleus in the hypoxic chemoreceptor cell. This study demonstrates the presence of classical protein kinase C enzymes in chemoreceptor cells. The intensity of the immunoreactivity may suggest a role for the classical protein kinase C signalling pathway in shaping the hypoxic response at the carotid body. However, this study failed to provide firm evidence of this.

Animals↗
PubMed2000

Prostaglandins E2 and I2 downregulate tumor necrosis factor alpha-induced intercellular adhesion molecule-1 expression in human oral gingival epithelial cells.

In the present study, we examined whether prostaglandin (PG) E2 and PGI2 regulated intercellular adhesion molecule-1 (ICAM-1) expression in human oral gingival epithelial cells stimulated with tumor necrosis factor alpha (TNF alpha). TNF alpha potently induced ICAM-1 expression in a dose- and time-dependent fashion. PGE2 and carbacyclin (a stable analogue of PGI2) significantly decreased ICAM-1 expression in TNF alpha-challenged oral gingival epithelial cells. Next, of the four subtypes of PGE2 receptors (EP1, EP2, EP3 and EP4), we examined which subtype(s) mediated inhibition of TNF alpha-induced ICAM-1 expression by PGE2. 11-deoxy-PGE2, an EP2/EP4 agonist, significantly suppressed TNF alpha-induced ICAM-1 expression, whereas butaprost, an EP2 agonist, sulprostone, an EP1/EP3 agonist, and ONO-AP-324, an EP3 agonist, caused no effect on it. By reverse transcriptase-polymerase chain reaction, expression of EP4 mRNA was detected in oral gingival epithelial cells. Dibutyryl cAMP, a cAMP analogue, and forskolin, a direct activator of adenylate cyclase, significantly inhibited TNF alpha-induced ICAM-1 expression in oral gingival epithelial cells. From these results, we suggest that PGE2 and PGI2 inhibit TNF alpha-elicited ICAM-1 expression by cAMP-dependent pathways via EP4 receptors and IP receptors, respectively.

Acetates↗
PubMed2000

Effects of intravenous immunoglobulin in a patient with intermittent thrombotic thrombocytopenic purpura.

We describe a patient with a 9-year history of thrombotic thrombocytopenic purpura (TTP) who exhibited four relapses. Intravenous immunoglobulin (IVIg) was effective for these four episodes. The patient was well and the laboratory findings were within normal ranges between each episode, although unusually large von Willebrand factor multimers were observed during remission. Our results suggest the usefulness of IVIg at the time of relapse in the treatment of patients with TTP who have multiple relapses over a long period.

Electrophoresis, Agar Gel↗
PubMed2000

Distinct immunohistochemical localization of two isoforms of Ca2+/calmodulin-dependent protein kinase kinases in the adult rat brain.

Ca2+/calmodulin-dependent protein kinase IV (CaM-KIV) is thought to be involved in regulating gene expression by phosphorylating various transcriptional factors. CaM-KIV as well as CaM-KI are activated upon phosphorylation by two distinct isoforms of Ca2+/calmodulin-dependent protein kinase kinases, CaM-KKs alpha and beta. In this study, we raised isoform-specific monoclonal antibodies against CaM-KKs and examined the immunohistochemical localization of CaM-KKs in the rat brain, compared with that of CaM-KIV. CaM-KK alpha-immunoreactivity was rather widely distributed in neurons throughout the brain, except cerebellar cortex. The highest levels of CaM-KK alpha-immunoreactivity were observed in the cerebral cortex, facial nucleus and motor neurons of the spinal cord. Moderate CaM-KK alpha-immunoreactivity was observed in the hippocampal formation, pontine nuclei and various brain stem nuclei including trigeminal, vestibular, cochlear and hypoglossal nuclei. In contrast, CaM-KK beta-immunoreactivity was relatively restricted in some neuronal populations. The highest levels of CaM-KK beta-immunoreactivity were observed in the cerebellar granule cell layer, and moderate immunoreactivity was observed in the cerebral cortex, hippocampal formation, caudate putamen, pontine nuclei, cochlear nucleus and molecular layer of the cerebellum. In contrast to the prominent nuclear localization of CaM-KIV, both isoforms of CaM-KKs were localized in the perikaryal cytoplasm, dendrites and nerve terminals, but not in the cell nuclei. The distinct localization of two isoforms of CaM-KKs suggests that the complicated mechanisms for activation of CaM-KIV by CaM-KKs may be exerted in region-specific manners as well as intracellularly.

Animals↗
PubMed2000

Structure of the mouse glutamate decarboxylase 65 gene and its promoter: preferential expression of its promoter in the GABAergic neurons of transgenic mice.

GABA is synthesized by glutamate decarboxylase (GAD), which has two forms, GAD65 and GAD67. To elucidate the molecular mechanisms of mouse GAD65 (mGAD65) gene expression, we isolated and characterized the mGAD65 gene. The mGAD65 gene was found to be divided into 16 exons and spread over 75 kb. The sequence of the first exon and the 5'-flanking region indicated the presence of potential neuron-specific cis-regulatory elements. We used transgenic mice to examine the expression pattern conferred by a 9.2-kb promoter-proximal DNA fragment of the mGAD65 gene fused to the bacterial lacZ reporter gene. Transgenic mice showed high beta-galactosidase activity specifically in brain and testis. They also showed characteristic patterns of transgene expression in olfactory bulb, cerebellar cortex, and spinal cord, a similar expression pattern to that of endogenous mGAD65. However, no transgene expression was observed in the ventral thalamus or hypothalamus, in which high mGAD65 gene expression levels have been observed. These results suggest that the 9.2-kb DNA fragment of the mGAD65 gene is associated with its tissue-specific expression and its targeted expression in GABAergic neurons of specific brain regions but that additional regulatory elements are necessary to obtain fully correct expression.

Amino Acid Sequence↗
PubMed2000

Suppressed tumorigenicity of human endometrial cancer cells by the restored expression of the DCC gene.

To obtain functional evidence for DCC as a tumour suppressor associated with endometrial cancer, the human DCC cDNA encoding a complete open reading frame (ORF) was transfected into highly tumorigenic human endometrial carcinoma cells, HHUA and Ishikawa in which DCC expression was completely deleted. Reconstituted expression of DCC in HHUA had little effect on in vitro growth, but suppressed tumour formation in mice completely. The clones from Ishikawa had abundant DCC expression similar to that in normal endometrium. Their growth in vitro was suppressed and showed apoptotic phenotype. Lower levels of DCC expression in the prolonged passaged clones did not induce apoptosis, but still had the potential to suppress tumorigenicity. These observations imply a role of DCC in regulation of normal endometrial cell growth, and categorize DCC as the tumour suppressor gene for endometrial cancer.

Animals↗
PubMed2000

High-frame-rate tissue harmonic imaging enhances anatomic M-mode sections of the left ventricle in short-axis view.

BACKGROUND: High-frame-rate echocardiography (HFRE) and tissue harmonic imaging (THI) may improve image quality, thereby enabling anatomic M-mode sections of left ventricular (LV) wall segments to be visualized in various planes in the short-axis view. OBJECTIVES: The goals of this study were to compare image quality between HFRE and conventional-frame-rate echocardiography (CFRE) and between fundamental imaging (FI) and THI, and to obtain anatomic M-mode values of basal short-axis LV segments from healthy subjects for use in the evaluation of abnormal segments in patients with myocardial infarction (MI). METHODS AND RESULTS: The study included 28 healthy subjects and 15 patients with MI who underwent 2-dimensional echocardiography with an ultrasonographic system equipped with THI and anatomic M-mode. Left ventricular image cineloops at the basal short-axis view that were obtained with 3 combinations of imaging techniques (FI + CFRE, FI + HFRE, and THI + HFRE) were digitized and displayed side-by-side in random order for comparison by blinded readers. M-mode sections were done in 3 planes: anteroseptal-posterior, inferoseptal-lateral, and anterior-inferior basal segments. The THI + HFRE combination showed the best image quality with significant reduction in noise artifacts, resulting in a good signal-to-noise ratio and good tractability of all LV segments by anatomic M-mode. In healthy subjects, significant intersegmental differences existed in the diastolic and systolic thicknesses and in the percent systolic thickening of LV segments. In patients with MI, LV systolic thickening was significantly decreased in abnormal segments. No significant differences were noted in ejection fraction and fractional shortening among the 3 anatomic M-mode planes. CONCLUSION: High-frame-rate tissue harmonic imaging improved image quality, thereby allowing reproducible anatomic M-mode measurements in various planes in the short-axis view and providing a convenient objective evaluation of global and regional LV function.

Adult↗
PubMed2000

Myocardial longitudinal motion by tissue velocity imaging in the evaluation of patients with myocardial infarction.

Left ventricular (LV) longitudinal shortening plays an important role in cardiac contraction and is invariably affected by the presence of coronary artery disease. Third-generation tissue velocity imaging (TVI) color-maps cardiac movement by obtaining mean velocities of LV segments from the same set of beats. The goals of this study were to characterize patterns of longitudinal myocardial motion velocity in healthy subjects and to use these patterns to evaluate abnormal segments of patients with myocardial infarction (MI). Included were 20 healthy subjects and 16 patients with MI who underwent a 2-dimensional Doppler echocardiography study. Myocardial velocity profiles were taken at the anulus, basal, mid, and apical segments of the septal and lateral walls in the apical view. Segmental velocity patterns from healthy subjects were compared with abnormal segments in patients with MI. Both lateral and septal walls of healthy subjects showed significant basal-apical myocardial velocity reductions in systolic shortening (Sm) and early and late diastolic lengthening (Em and Am) and a basal-apical increase in the Em/Am ratio. The lateral wall had greater Sm and Em velocities than the septal wall. The Sm and Em velocities and the Em/Am ratio were significantly reduced in the abnormal segments in patients with MI. Latent lateral wall ischemia may have been detected in 5 of 9 patients with septal infarction, showing reduced Sm velocity in apparently normal lateral walls. In conclusion, TVI objectively quantifies directional and incremental changes in myocardial movement that are useful in evaluating global and regional myocardial function, and it may play a role in the detection of early myocardial ischemia.

Adult↗
PubMed2000

Polymerization of actin induced by a molar excess of ATP in a low salt buffer.

The polymerization of actin induced by dilution has previously been reported, where a 1000-fold molar excess of ATP over actin resulted when actin was diluted to 4.0 microg/ml in low salt buffer A (0.1 mM ATP, 0.1 mM CaCl2, 2 mM Tris-HCl, pH 8.0, 5 mM 2-mercaptoethanol, 1 mM NaN3). Filaments formed by the addition of ATP to a 1000-fold molar excess over actin in buffer B (0.1 mM CaCl2, 2 mM Tris-HCl, pH 8.0, 1 mM NaN3) were then separated by gel-filtration. When ATP was removed from these filaments using Dowex-1, depolymerization occurred. Thus, the reversible polymerization induced by the dilution of actin or by addition of ATP can be ascribed to the binding of ATP at the low affinity site of actin.

Actins↗
PubMed2000

Wild type ApoA-II gene does not rescue senescence-accelerated mouse (SAMP1) from short life span and accelerated mortality.

Biochemical and genetic data suggest that the Apoa2c allele of the apolipoprotein A-II gene causes severe senile amyloidosis (AApoAII) in SAMP1, a mouse model for accelerated senescence. We analyzed the effects of replacement of Apoa2c in SAMP1 mice with non-amyloidogenic Apoa2b on amyloidosis, lipoprotein metabolism, and progression of senescence using a congenic strain, P1.R1-Apoa2b, which has the Apoa2b chromosome region of SAMR1 in the genome of SAMP1. Age-associated amyloid deposition was not observed, but plasma concentrations of apoA-II protein and HDL-cholesterol decreased with age in P1.R1-Apoa2b. P1.R1-Apoa2b showed lower scores of senescence than did SAMP1. However, the life span and mortality rate doubling time were similar in P1.R1-Apoa2b and SAMP1. These results suggest that replacement of Apoa2c with non-amyloidogenic Apoa2b does not rescue SAMP1 mice from a short life span and accelerated mortality.

Aging↗
PubMed2000

CT-assisted transbronchial brachytherapy for small peripheral lung cancer.

Transbronchial brachytherapy for small peripheral lung cancer was developed with the use of the CT-guided bronchoscopy technique. Under CT guidance, an applicator carrying a dummy source was introduced into a lesion and stabilized. A radioactive source was then delivered through the applicator using a high dose rate remote afterloading system. For multiple radiation fractions, a marker was placed immediately under the pleura in a peripheral bronchus penetrating the lesion using the CT-guided barium marking technique. During brachytherapy, an applicator with a dummy source was inserted under fluoroscopic guidance up to the marker. A radioactive source was subsequently delivered. CT-assisted transbronchial brachytherapy allows radiation to be delivered from inside a lesion. This minimizes radiation damage to noncancerous tissue and offers distinct advantages over conventional radiation techniques.

Adenocarcinoma↗
PubMed2000

Inflammatory pseudotumor of the spleen: a case report.

We report on an inflammatory pseudotumor of the spleen. A 72-year-old woman visited our hospital complaining of nausea. Physical examination and laboratory investigations were unremarkable. Ultrasonography, computed tomography, magnetic resonance imaging and angiography showed a hypovascular splenic mass measuring about 5 cm in diameter with a calcification in the center of the lesion. Splenectomy was performed. The removed spleen, weighing 145 g, contained a tan-white, circumscribed mass, measuring 6.2 x 5.5 x 5.3 cm. Histologically, the splenic mass was composed of an admixture of inflammatory cellular elements, predominantly plasma cells and lymphocytes with hyalinization, fibrosis, lymph follicles and multinuclear giant cells, suggestive of a inflammatory pseudotumor. The patient is currently alive and asymptomatic, 24 months after surgery. Inflammatory pseudotumors of the spleen are extremely rare and only 39 cases have been reported in the medical literature.

Aged↗
PubMed2000

Lung carcinoma with polypoid growth in the main pulmonary artery: report of two cases.

Invasion into the lumen of the main pulmonary artery is an uncommon mode of extension in lung carcinoma and its prognostic significance remains unclear. We describe here two resected cases of lung carcinoma that showed such a rare tumor spread. Although a preoperative evaluation, such as angiography or perfusion scan of the lung, had shown a significant decrease in circulation, we could not diagnose the intraluminal tumor growth preoperatively. Pneumonectomy was finally needed to perform a curative operation. The tumors were centrally located and showed polypoid growth in the main pulmonary artery. Postoperative pathological examination revealed the tumors to be adenosquamous carcinoma of the lung in both cases. No intrapulmonary metastases were detected. One patient is doing well with no signs of recurrence after a follow-up period of 10 years. Although intra-arterial polypoid growth of lung carcinoma is extremely rare, such tumor extension should be considered preoperatively to perform a curative surgical resection, especially when the tumor is centrally located. While arterial invasion is generally an ominous prognostic factor, curative surgical resection would offer a good prognosis, even for lung carcinoma invading the main pulmonary arterial trunk.

Aged↗
PubMed2000

Hemangioma of the rib: a case report.

A case of hemangioma of the left seventh rib is presented. In January 1999, a 59-year-old woman presented with an enlarged costal mass which had been followed up for 4 years. Preoperative examination suggested chondrosarcoma because of tumor growth beyond the disrupted bony cortex. She underwent resection of the left seventh rib along with the sixth and seventh intercostal muscles and reconstruction of the chest wall defect. The pathological diagnosis of the lesion was hemangioma. She was discharged after an uneventful postoperative course. There has been no evidence of recurrence after a 14-month follow-up. Tumor growth beyond the disrupted bony cortex was a characteristic feature by both imagery and pathological examination in this case. This case represents a difficulty of a preoperative definite diagnosis of the chest wall tumors by imagery alone.

Bone Neoplasms↗
PubMed2000

Cell mediators of inflammation in the Alzheimer disease brain.

Lesions of Alzheimer disease are associated with low-grade but sustained inflammatory responses. Activated microglia agglomerate in the center of senile plaques. Reactive astrocytes marginate the amyloid beta-protein (A beta) deposits and extend their processes toward the center of plaques. Both microglia and astrocytes are known to secrete a wide variety of molecules involved in inflammation and are potential sources of proinflammatory elements in the brain. Dystrophic neurites occur in senile plaques with such glial reactions, suggesting the relevance of inflammatory responses to the neuronal degeneration in Alzheimer disease. Activated glial cells are, therefore, targets of anti-inflammatory therapy of Alzheimer disease. However, evidence also indicates that these cells eliminate A beta from the brain. A beta is produced continuously in both the normal and the AD brain. Under normal conditions, A beta is removed successfully before it accumulates as extracellular amyloid fibrils. Even in Alzheimer disease, a large portion of A beta may be cleared from the brain with a small portion being left and deposited as neurotoxic senile plaques. Both in vivo and in vitro studies showed the effective uptake of A beta by microglia. Before clinical application, it must be determined whether the treatment that suppresses glial activation and inflammatory responses inhibits A beta removal by glial cells.

Alzheimer Disease↗