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Biomedical subjects

H Kondo

Publications and source records attributed to H Kondo.

At least 505 records · Page 28Linked to original sources

Localization of mRNA for phosphatidylinositol 3-kinase in brain of developing and mature rats.

In the adult brain, the gene expression for phosphatidylinositol 3-kinase was weak in almost all neurons with relatively high levels in the olfactory bulb, hippocampus, and cerebellum. On the embryonic days high levels of the gene expression were found throughout the entire neuraxis, then decreased gradually to adult levels during postnatal development. The present finding suggests that phosphatidylinositol 3-kinase may contribute not only to neurogenesis but also to some important physiological roles in differentiating and mature neurons.

Amino Acid Sequence↗

Fas antigen expression in brains of patients with Alzheimer-type dementia.

Fas antigen (CD95) is a cell surface protein that mediates apoptosis. We have investigated the immunohistochemical localization of Fas antigen in postmortem brain tissue from control subjects, patients with Alzheimer-type dementia (ATD), and from a few patients with diffuse Lewy body disease, progressive supranuclear palsy and adrenoleukodystrophy. In all brains, including controls, vascular endothelial cells and residual blood plasma were weakly stained. In ATD brains, senile plaques and a small number of star-like cells were brains of patients with neurological diseases other than ATD. In double immunostaining for Fas and glial fibrillary acidic protein (GFAP), a small number of cells were positive for both antigens. The majority of Fas-positive astrocytes were, however, negative for GFAP. This implies the downregulation of GFAP production in these cells. Doubly labeled astrocytes were also found around senile plaques, suggesting that the Fas immunoreactivity in senile plaques was derived from astrocytic membranes. The results of this study indicate that Fas antigen is expressed by a subset of reactive astrocytes in degenerative neurological diseases. Such astrocytes may undergo the Fas-mediated apoptotic process.

Aged↗

Numerous glial fibrillary tangles in oligodendroglia in cases of subacute sclerosing panencephalitis with neurofibrillary tangles.

Both neurons and oligodendroglia are preferentially infected in subacute sclerosing panencephalitis (SSPE). Massive argyrophilic and tau-positive glial fibrillary tangles (GFT) were found in oligodendroglia in two autopsy cases of SSPE with neurofibrillary tangles (NFT). GFT shared common phosphorylated tau-epitopes with NFT, but were negative for ubiquitin. Electron microscopically, GFT consisted of compact bundles of irregularly woven tubules. Thus, GFT in SSPE differed from NFT showing regular constriction of tubules and from GFT in some other cytoskeletal disorders in which GFT reportedly consisted of straight tubules.

Adolescent↗

Small adenocarcinoma of the lung. Histologic characteristics and prognosis.

BACKGROUND: Although there are many reported prognostic indicators for pulmonary adenocarcinoma, the clinicopathologic characteristics and prognostic factors of early stage adenocarcinoma have not been evaluated fully, except for several studies of nonmucinous and sclerosing bronchioloalveolar carcinoma. METHOD: Two hundred thirty-six surgically resected small peripheral adenocarcinomas measuring 2 cm or less in greatest dimension were reviewed using a simple histologic classification of six types based on tumor growth patterns. RESULTS: Type A (localized bronchioloalveolar carcinoma [LBAC]) (n = 14) revealed replacement growth of alveolar-lining epithelial cells with a relatively thin stroma. In type B (LBAC with foci of structural collapse of alveoli) (n = 14), fibrotic foci due to alveolar collapse were observed in tumors of LBAC. Type C (LBAC with foci of active fibroblastic proliferation) (n = 141) was the largest group in this study, and foci of active fibroblastic proliferation were evident. Type D (poorly differentiated adenocarcinoma), type E (tubular adenocarcinoma) and type F (papillary adenocarcinoma with a compressive growth pattern) (n = 61) showed compressive and expanding growth. Types A and B showed no lymph node metastasis and the most favorable prognosis (100% 5-year survival) of the six types. CONCLUSION: Histologic types A and B are thought to be in situ peripheral adenocarcinoma, whereas type C appears to be an advanced stage of types A and B. Conversely, types D, E, and F are small advanced adenocarcinomas with a less favorable prognosis.

Adenocarcinoma↗

Effects of aging and dietary restriction on activity of monkey serum in promoting fibroblast migration.

In order to determine whether serum modified cellular aging in vivo, we previously studied the effects of serum from various mammals of different ages on cell functions such as proliferation and migration, and reported that cell migration was more greatly inhibited by serum from old donors than cell proliferation [1]. Moreover, since dietary restriction has been reported to extend lifespan and slow the aging rate of some animals [2], we wondered whether sera from dietary restricted and control monkeys of various ages might exhibit reduced aging effects on cell migration. When serum from young adult (3-5 years old) monkeys was added to plain medium, the migration of human fetal skin fibroblasts was very strongly inhibited compared to FBS. Surprisingly, sera from adult (6-11 years old) and old (more than 18 years old) monkeys caused significantly less migration-inhibitory activity than serum from young adult monkeys although sera from adult and old monkeys were much more inhibitory to cell migration than FBS. Dietary restriction only caused marginal effects on serum migration-promoting activity in a few monkey groups. The inhibition of cell migration caused by monkey serum was not brought about by cytotoxic effects since monkey serum stimulated cell proliferation as well as fetal bovine serum. These results indicate that the effects of aging on monkey serum migration-promoting activity are much more pronounced than those of dietary restriction.

Aging↗

Digital subtraction high-frame-rate echocardiography in detecting delayed onset of regional left ventricular relaxation in ischemic heart disease.

BACKGROUND: Because left ventricular (LV) diastolic function is impaired before systolic function in patients with ischemic heart disease and because ischemic heart disease is constituted of regional rather than global abnormalities of the left ventricle, measures of LV regional diastolic dysfunction, if possible, should provide the most sensitive assessment of the coronary involved region. The objectives of this study are to clarify whether high-frame-rate two-dimensional echocardiography, combined with digital subtraction image processing, may be used to visualize regional LV relaxation abnormalities in patients with ischemic heart disease and to clarify whether this technique provides a measure for the noninvasive assessment of the coronary involved region. METHOD AND RESULTS: In 30 normal subjects and 59 patients with ischemic heart disease, two-dimensional echocardiograms obtained at a rate of 60 frames per second were provided on line for digital subtraction analysis, with which digitized images were continuously subtracted on a frame-by-frame basis. The subtracted images were analyzed to determine the onset of the segmental outward motion of the LV wall in early diastole in each of 16 segments per subject. Regional relaxation index, defined as the interval from the second heart sound to the onset of outward wall motion, was significantly prolonged in the coronary involved segments compared with the normal segments (36.3 +/- 18.0 versus 101.2 +/- 34.0 ms, P < .01). The prolongation in the regional relaxation index was observed even in the coronary involved segments without reduction in systolic wall motion. When a cutoff level of 50.0 ms was used, coronary involved segments could be distinguished from normal or border segments with a sensitivity of 92% and a specificity of 81%. CONCLUSIONS: Digital subtraction high-frame-rate echocardiography may be used to visualize regional LV relaxation abnormalities in patients with ischemic heart disease. The time interval from the second heart sound to the onset of the segmental outward motion of the LV wall (regional relaxation index) obtained with this technique provides a noninvasive and accurate measure for assessing coronary involved regions.

Adult↗

Noninvasive assessment of left ventricular relaxation using continuous-wave Doppler aortic regurgitant velocity curve. Its comparative value to the mitral regurgitation method.

BACKGROUND: The most established parameters of left ventricular (LV) relaxation are peak negative value of the first derivative of LV pressure (-dP/dtmax) and the time constant of isovolumic LV pressure fall. The instantaneous pressure gradient between the aorta and the LV during diastole can be calculated from the continuous-wave Doppler aortic regurgitant velocity spectrum. Because the fluctuation of aortic pressure during LV isovolumic relaxation is negligibly minor and because LV minimal pressure is negligibly low, LV pressure during the isovolumic relaxation period may be derived from the continuous-wave Doppler aortic regurgitant velocity spectrum. This study was designed to clarify whether analysis of continuous-wave Doppler aortic regurgitation recording provides accurate measures of LV relaxation over a wide range of LV function and to determine comparative values of aortic and mitral regurgitation methods in the assessment of LV relaxation. METHODS AND RESULTS: In eight mongrel dogs with acute ischemic LV dysfunction, the continuous-wave Doppler aortic regurgitant velocity spectrum was recorded simultaneously with high-fidelity LV and aortic pressures, while the continuous-wave Doppler mitral regurgitant velocity spectrum was recorded simultaneously with high-fidelity left atrial and LV pressures. The aortic regurgitant velocity spectrum was provided for the determination of Doppler-derived mean rate of LV pressure fall in 20 ms after the onset of aortic regurgitation (delta P/delta t-AR) and the time interval from the onset of aortic regurgitation to the point at (1-1/e)1/2 of the maximal aortic regurgitant velocity as an estimate of the time constant. The mitral regurgitant velocity spectrum was provided for Doppler-derived mean rate of LV pressure fall in 20 ms after the point of -dP/dtmax (delta P/delta t-MR) and the time interval from the point of -dP/dtmax to the point with mitral regurgitant velocity of (1/e)1/2 of the mitral regurgitant velocity at the point of -dP/dtmax as an estimate of the time constant. delta P/delta t-AR and delta P/delta t-MR correlated well with catheter-derived -dP/dtmax (r = .92, r = .98, P < .01, respectively). The time constant derived from aortic and mitral regurgitant velocity spectra (tau-AR and tau-MR) also correlated well with catheter-derived time constant (r = .84, r = .76, P < .01, respectively). However, a mean difference of the catheter-derived time constant minus tau-MR was larger than tau-AR (29 +/- 30 versus 4 +/- 17 ms, P < .01, presented as mean +/- 2 SD). CONCLUSIONS: LV relaxation can be assessed from the continuous-wave Doppler aortic regurgitant velocity spectrum. The aortic regurgitation method provides an even more accurate estimate of the time constant compared with the mitral regurgitation method, particularly in the presence of LV dysfunction.

Animals↗

Fetal-adult phenotype transition, in terms of the serum dependency and growth factor requirements, of human skin fibroblast migration.

Since the migration of human fetal skin fibroblasts into a denuded area of a cell monolayer has been demonstrated to be serum-independent (fetal phenotype), whereas that of adult-donor skin fibroblasts is serum-dependent (adult phenotype), a study was carried out to determine at which life stage the fetal-adult phenotype transition, in terms of serum dependency of human skin fibroblast migration, occurs. The results demonstrated that this phenotype transition occurred before birth, and, therefore, the fetal skin fibroblast phenotype differed from those of infant-, child-, adult-, and elderly-donor skin fibroblasts. But, the fetal-, child-, and adult-donor skin fibroblast phenotypes did not change during in vitro aging. On the other hand, the growth factor requirement for human skin fibroblast migration changed similarly to the serum dependency for fibroblast migration: the signal for fibroblast migration changed from basic fibroblast growth factor for the fetal phenotype to platelet-derived growth factor for the adult phenotype.

Adult↗

Detection of anti-bovine beta 2-glycoprotein I antibody in sera from patients with antiphospholipid syndrome.

We studied and characterized anti-bovine beta 2-glycoprotein I antibodies (aB beta 2-GPI) in sera from patients with antiphospholipid syndrome (APS) by ELISA. Bovine beta 2-glycoprotein I (beta 2-GPI) was purified by heparin affinity and DEAE ion-exchange chromatography, and identified on immunoblots using a monoclonal antibody against human beta 2-GPI and by amino acid sequence analysis. aB beta 2-GPI levels in the sera from 36 APS patients were measured by ELISA using purified bovine beta 2-GPI as an antigen. The mean +/- standard deviation level of aB beta 2-GPI was 17.4 +/- 22.0 units in the 58% of APS patients who were positive. There was a significant correlation (P = 0.003) between aB beta 2-GPI and anticardiolipin antibody (aCL) levels. aB beta 2-GPI from the sera of patients with APS was inhibited by bovine beta 2-GPI itself. Purified IgG from the sera of patients with APS showed that bovine beta 2-GPI was capable of acting as a cofactor for aCL. Purified bovine beta 2-GPI was useful antigen for conventional ELISA. aB beta 2-GPI may contribute to the further development of aCL analysis and to the understanding of the pathogenesis of APS.

Adult↗

White matter amyloid in Alzheimer's disease brain.

Amyloid beta-protein (A beta) deposits in the white matter were investigated by the double immunohistochemical staining for A beta and neuritic, glial or vascular components. Reactive astroglia and neurite abnormality were absent around A beta deposits in the white matter (w-A beta) even those with a core. The association of w-A beta with blood vessels was not consistent. Aggregates of activated microglia were found to be the sole but a consistent accompaniment of A beta deposits even in the absence of other components such as neuron, synapse, neurite abnormality and reactive astroglia, as observed in the white matter. This suggests that the aggregates of activated microglia most likely represent one of the factors promoting the process of A beta deposition.

Alzheimer Disease↗

A study of dementia with argyrophilic grains. Possible cytoskeletal abnormality in dendrospinal portion of neurons and oligodendroglia.

Two mildly demented patients with emotional disorder presented massive cortical argyrophilic grains (ArG) in the limbic area and coiled bodies mainly in the white matter. Immunohistochemically, the ArG consisted of partially ubiquitinated full-length phosphorylated tau. A modified Gallyas-Braak method, used after potassium permanganate and oxalic acid pretreatment, revealed many filiform, knobby or pleomorphic spine-like appendages on the ArG. Double immunohistochemical staining using anti-tau with either anti-microtubule-associated protein 2 or anti-neurofilament 200K revealed that ArG were intimately associated with dendrites rather than with axons. Electron microscopic studies with tau immunohistochemistry and the Gallyas-Braak method revealed that the ArG were composed of bundles of smooth tubules of 25-nm diameter. The coiled body-bearing cells had the morphological characteristic of oligodendroglia. These results indicate that the presence of ArG is a cytoskeletal abnormality affecting predominantly the dendrospinal portions of neurons. A survey of diseases with cytoskeletal disorders revealed that a small number of similar argyrophilic granular structures are sometimes observed in progressive supranuclear palsy, Pick's disease with Pick bodies and corticobasal degeneration. Dementia with ArG is thought to be a unique cytoskeletal abnormality associated predominantly with the dendrospinal portions of neurons and oligodendroglia.

Aged↗

Thorn-shaped astrocytes: possibly secondarily induced tau-positive glial fibrillary tangles.

Argyrophilic and tau-positive abnormal structures occurring in glial cells are called glial fibrillary tangles. In the astrocyte, a conspicuous tau-positive structure is known to appear in progressive supranuclear palsy (PSP). In this report, another type of argyrophilic and tau-positive astrocytes is reported. The morphology of this new type is quite different from that of the previously reported tau-positive astrocyte in PSP and they are designated here as thorn-shaped astrocytes (TSA). TSA have an apparently argyrophilic cytoplasm with a few short processes and often have a small eccentric nucleus, whose appearance resembles that of a reactive astrocyte. Immunohistochemically, TSA are positive to anti-tau antibodies but are negative for ubiquitin. Simultaneous immunostaining revealed the coexistence of tau and glial fibrillary acidic protein epitopes in the same cytoplasm. Electron microscopically, bundles of 15-nm straight tubules were included in the cytoplasm together with abundant glial filaments. In the vicinity of a cluster of TSA, related structures of perivascular or subpial tau-positive linings, which correspond to astrocytic end-feet, are sometimes observed. In almost all cases, a few TSA are generally located in a confined area of subpial and subependymal regions. Although TSA appear to be intimately associated with some diseases, they are also found in a wide range of cytoskeletal disorders including the aged brain with neurofibrillary tangles. TSA are presumed to be a secondary induced product in relation to astrocytic reaction.

Aged↗

Alzheimer-type pathology in melanin-bleached sections of substantia nigra.

Bleaching of melanin prior to Gallyas staining enabled us to detect an unexpectedly large number of neurofibrillary tangles (NFTs; 62 and 50 NFTs in the upper and the lower substantia nigra, respectively, mostly in the neuronal cytoplasm of the medial zona compacta) in brains of patients who had had Alzheimer's disease. Amyloid-like deposits were quite scarce. In Alzheimer's disease it has been commonly observed that other subcortical nuclei projecting widely to the cerebral cortex also contain a large number of NFTs, although they have few amyloid deposits. In these subcortical nuclei retrograde degeneration may initially affect intraneuronal processes, leading to the preferential development of NFTs in the neuronal cytoplasm.

Aged↗

Autoantibody against a 78 kDa membrane protein of HepG2 cell in the sera of patients with alcoholic liver diseases.

Sera from 14 normal control subjects, 30 patients with alcoholic liver diseases (fatty liver, n = 8; hepatitis, n = 13; liver cirrhosis, n = 9), 7 controls with chronic hepatitis B, and 8 controls with chronic hepatitis C were masured for their concentrations of antibodies against HepG2 membrane protein by a binding assay utilizing 125I-labeled protein A. When the cut-off level was set as the mean value plus 2 SD of normal control subjects, the incidence of positivity was 75%, 69.2%, and 77.8% in patients with alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis, respectively. Both the mean serum antibody values and the positive incidence were significantly higher in patients with alcoholic liver diseases than in either the normal controls or in the control patients with chronic hepatitis. Sodium dodecylsulfate polyacrylamide gel electrophoresis of 125I-labeled HepG2 membrane protein precipitated with IgG from patients with alcoholic liver diseases revealed an immunoreactive band at a molecular weight of 78,000 daltons (gp78). The antibody activity remained after immunoabsorption by human liver-specific lipoprotein (LSP) but decreased when HepG2 cells were pre-treated with trypsin or neuraminidase. Consequently, gp78 appears to be a glycoprotein distinct from LSP, and is specifically recognized by IgG from patients with alcoholic liver diseases. This assay may provide a new system to measure autoantibody to hepatocytes in alcoholic liver diseases.

Autoantibodies↗

Intraventricular dispersion of early diastolic filling: a new marker of left ventricular diastolic dysfunction.

Mitral flow velocity patterns are frequently "normalized" by the alteration in the loading condition even in the presence of left ventricular (LV) diastolic dysfunction. In addition, a simple index, the ratio of mitral peak early diastolic flow velocity to mitral peak flow velocity at atrial contraction, is not obtainable in patients with atrial fibrillation (Af). Thus these limitations hamper the value of analyzing the mitral flow velocity pattern in the assessment of abnormal LV diastolic characteristics. This study was designed to elucidate the hypothesis that peak early diastolic flow velocity decreases progressively from the base to the apex in patients with LV diastolic dysfunction. Regional diastolic flow velocity patterns at 1, 2, or 3 cm from the mitral tip toward the apex were simultaneously recorded with the mitral flow velocity pattern by using multigate pulsed Doppler echocardiography in 42 subjects with normal LV function (31 normal volunteers and 11 patients with Af only), 17 patients with hypertensive heart disease, and 22 patients with dilated cardiomyopathy. In the normal subjects early diastolic flow velocity at the mitral tip was maintained at the positions 1 to 3 cm away from the tip into the LV cavity. In contrast, regional peak early diastolic flow velocity progressively decreased toward the apex in patients with hypertensive heart disease and dilated cardiomyopathy. These findings were observed even in patients with a normalized mitral flow velocity pattern or those with Af. Thus the assessment of the intraventricular decrease in peak early diastolic flow velocity may be useful in detecting LV diastolic dysfunction, particularly in patients with Af or a "normalized" mitral flow velocity pattern.

Adult↗

Doppler echocardiographic pulmonary venous flow-velocity pattern for assessment of the hemodynamic profile in acute congestive heart failure.

The hemodynamic profile of congestive heart failure (CHF) is best described in terms of its two primary sets of hemodynamic parameters, that is, left atrial pressure and cardiac output, each of which has a specific and independently variable hemodynamic cause. To assess whether analysis of the mitral and/or pulmonary venous flow-velocity patterns provides valuable information in the noninvasive assessment of the hemodynamic profile of CHF, these patterns were obtained by using the transthoracic approach in 18 patients with acute CHF with simultaneous measurements of catheter-derived mean pulmonary capillary wedge pressure and thermodilution cardiac index. Measurements were repeated on two occasions in each case: at the acute stage of CHF and 1 to 5 days after treatment. Peak diastolic pulmonary venous forward flow velocity was higher, the ratio of pulmonary venous systolic to diastolic peak forward flow velocity was lower, and the ratio of mitral early diastolic to late diastolic flow velocity was greater in patients with higher mean pulmonary capillary wedge pressure (r = 0.80, n = 36, p < 0.01; r = -0.69, n = 36, p < 0.01; r = 0.71, n = 36, p < 0.01). Peak systolic pulmonary venous forward flow velocity and time-velocity integral of the systolic pulmonary venous flow wave were greater in patients with larger cardiac index (r = 0.80, n = 36, p < 0.01; r = 0.62, n = 36, p < 0.01). In conclusion, two primary sets of hemodynamic parameters, that is, left atrial pressure and cardiac output, can be estimated with Doppler pulmonary venous flow parameters in patients with acute CHF.

Acute Disease↗

Toluene induces behavioral activation without affecting striatal dopamine metabolism in the rat: behavioral and microdialysis studies.

We examined the effects of toluene on the release of dopamine (DA) and its metabolites in rat striatum using microdialysis. Intraperitoneal injection of 800 mg/kg toluene significantly increased motor activity in rats, as did methamphetamine (MAP) (1 mg/kg). However, 800 mg/kg toluene did not affect the extracellular levels of DA, 3,4-dihydroxyphenylacetic acid, homovanillic acid, or 5-hydroxyindoleacetic acid. This is in contrast to MAP, which significantly increased extracellular DA and decreased the extracellular levels of its metabolites. These results suggest that toluene-induced behavioral augmentation may not be associated with alterations in DA or serotonin neurochemistry such as are associated with MAP-induced behavioral augmentation.

Animals↗

Localization of mRNAs of voltage-dependent Ca(2+)-channels: four subtypes of alpha 1- and beta-subunits in developing and mature rat brain.

The heterogeneous gene expression for four subtypes of alpha 1 (A,B,C,D)- and beta (beta 1,beta 2,beta 3,beta 4)-subunits of voltage-dependent calcium channels was demonstrated in developing and adult rat brain by in situ hybridization histochemistry. In the adult rat brain the gene expression for A- and B-subtypes was predominant in the cerebellar cortex and hippocampal neuronal layers, with the A-subtype expressed most intensely in the Purkinje cells, while the expression for C- and D-subtypes was predominant in the olfactory mitral and granule cells and the dentate granule cells. The expression of beta 1-mRNA was prominent in the olfactory mitral cells and dentate granule cells whereas that of beta 2-mRNA was evident in the hippocampal neuronal layers and cerebellar Purkinje cells. The expression of beta 3-mRNA was prominent in the olfactory mitral and internal granule cells and medial habenula, whereas that of beta 4-mRNA in the olfactory mitral cells and cerebellar Purkinje and granule cells. Comparison between the expression patterns for individual alpha- and beta-subunits suggests that the beta 4-subunit contributes to P-type channel, whereas the beta 1- and beta 3-subunits contribute respectively to D- and C-subtypes of L-type channels, although dissociation in the expression patterns were also noted in several brain regions. In addition to neuronal populations, the gene expression for the C-subtype of L-type channel was detected at substantial level in glial cells. In developing brains, the genes for the all subtypes of alpha 1- and beta-subunits were expressed in the mantle zones, but not the ventricular zones, of the entire neuraxis and the expression was more or less attenuated during early postnatal periods in most of the brain regions except for the olfactory bulb, hippocampus and cerebellar cortex, suggesting that the Ca(2+)-channels are intimately involved in the neuronal differentiation.

Age Factors↗