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H Okazaki

Publications and source records attributed to H Okazaki.

At least 127 records · Page 7Linked to original sources
PubMed1996

[Importance of interstitial lung disease in collagen vascular disease: analysis of outcome].

We studied length of survival and related clinical findings in 715 inpatients with collagen-vascular diseases (1984 through 1994), the diagnostic Kaplan-Meier analysis showed that patients with polymyositis/dermatomyositis and those with systemic sclerosis did not survive as long as those with other types of collagen-vascular disease. Of the patients who died 37% died of respiratory failure due to interstitial lung disease. Patients with interstitial lung disease had better outcomes than did those with idiopathic interstitial pneumonia: they were younger, had higher initial vital capacities, and fewer episodes of acute exacerbation of lung disease than did those with idiopathic interstitial pneumonia. Among patients with interstitial lung disease, those who died of polymyositis/dermatomyositis did so within 1 year, but those who died of systemic sclerosis lived longer. Interstitial lung disease is an important prognostic factor in collagen-vascular disease, and needs further evaluation.

Cause of Death↗
PubMed1995

Similar rates of production of T and B lymphocytes in the bone marrow.

The rate of renewal of T lymphocytes in the bone marrow of euthymic C57BL/Ka and athymic nu/nu BALB/c mice was estimated by in vivo labeling with bromodeoxyuridine. T lymphocytes accounted for 16-18% of marrow cells in euthymic mice as judged by immunofluorescent staining with monoclonal antibodies for Thy-1, CD3, and alpha/beta T cell antigen receptor markers. About 70% of marrow cells expressed receptors (Mac-1, Gr-1, B220) for myeloid, macrophage, and B lineage cells. Approximately 13% of cells in the athymic bone marrow expressed alpha/beta T cell receptors. Sorted marrow T cells proliferated in response to stimulation with anti-alpha/beta antibodies in vitro and showed functional rearrangements of V beta and J beta genes. Sorted non-T cells did not respond to stimulation in vitro, and all V beta and J beta gene rearrangements identified were nonfunctional. In vivo labeling studies indicated that approximately 17 x 10(6) bone marrow T cells are renewed daily in euthymic mice and approximately 14 x 10(6) are renewed in athymic mice. Approximately 11 x 10(6) mature B cells (immunoglobulin M+) are renewed daily in the bone marrow of the latter mice. To determine whether marrow precursors can give rise to T cells directly, marrow cells from euthymic and athymic mice were depleted of T cells by cell sorting and incubated in vitro for 48 h in the absence of exogenous growth factors or thymic stromal cells. Examination of the cells after culture showed that 10-12% stained brightly for alpha/beta T cell receptors. Although functional rearrangements of V beta and J beta genes were not detected before culture, the majority of rearrangements were functional after culture. The emergence of the bright alpha/beta T cells in culture was dependent on depletion T cells from the marrow cells before culture. The results suggest that most marrow T cells are generated in the marrow itself.

Amino Acid Sequence↗
PubMed1995

Erythromycin suppresses interleukin 6 expression by human bronchial epithelial cells: a potential mechanism of its anti-inflammatory action.

We evaluated the effects of several antibiotics on IL-6 expression by human bronchial epithelial cells, potent sources of this proinflammatory cytokine important in airway inflammation. Among those tested, erythromycin (EM) and clarithromycin (CAM) uniquely suppressed mRNA levels as well as the release of IL-6 at the therapeutic and non-cytotoxic concentration (10(-6)M). Our findings suggested that these macrolide antibiotics had suppressive effect on cytokine expression in human cells, and this new mode of action may have relevance to their clinical effectiveness in airway inflammatory diseases.

Anti-Bacterial Agents↗
PubMed1995

Structural effect of galactose residue in synthetic glycoconjugates on interaction with rat hepatocytes.

N-p-Vinylbenzyl-O-beta-D-galactopyranosyl-(1,4)-D-gluconamide++ + (PVLA) has been used as an asialoglycoprotein model polymer. Rat hepatocytes expressing asialoglycoprotein receptors are capable of binding to hydrophobic plastic dishes coated with PVLA. PVLA, water-soluble polystyrene derivatives bearing galactose residues preferentially adsorb to plastic plates made of polystyrene rather than those of poly(methyl methacrylate). Hence, we modified chitosan beads with linear chains composed of a long alkyl or phenyl moiety to study the effect of structural variations of adsorbed PVLA, and investigated the extent of hepatocyte attachment to the hydrophobic beads coated with PVLA. The attachment was independent of the amount of immobilized PVLA; rather, it was dependent on the hydrophobicity of the beads with PVLA. To simplify the surface of the hydrophobic beads with PVLA, galactopyranoses were covalently linked to chitosan beads via hydrophobic spacer arms, and hepatocyte attachment was compared among the prepared beads. The beads with spacer arms containing phenylalanine and a phthalic moiety showed increased hepatocyte attachment, which was elicited by galactose residues on the beads. These results suggest that rotational restriction or stiffness and hydrophobicity due to the phenyl moiety are essential to enhance the specificity of terminal galactose in PVLA. This analysis contributes to the design and optimization of an artificial ligand for cellular receptors recognizing sugar moieties.

Animals↗
PubMed1995

Multichannel detection of magnetic compound action fields with stimulation of the index and little fingers.

Magnetic compound action fields (CAFs) over the right arm were measured from 63 sensor positions with two 7-channel SQUID gradiometer systems following electrical stimulation of the index and little fingers as well as the ring finger separately. The wave forms of the CAFs were primarily biphasic, corresponding to the depolarization and repolarization currents of the stimulated nerves. Maximum amplitudes of the CAFs were 60-140 fT for the index finger stimulation and 40-90 fT for the little finger stimulation. The field mapping of the CAFs revealed a propagating quadrupolar pattern with different distributions for the index and little fingers. The results agree with the anatomical location of the median and ulnar nerves for the index and little finger stimulation respectively. The isofield maps, due to ring finger stimulation, showed complex patterns as a result of simultaneous activation of the median and ulnar nerves. By comparing the amplitudes of the maxima of the CAFs due to index finger stimulation with those after median nerve stimulation at the wrist, the numerical ratios of the constituent digital nerve fibers for the index finger within the median nerve at the wrist were estimated. The ratios of 0.14-0.41 (mean 0.27), determined with measurement of the CAFs, are fairly consistent with those calculated from the reported histological data.

Adult↗
PubMed1995

Novel function of prostaglandins as inducers of gene expression of HGF and putative mediators of tissue regeneration.

Prostaglandins (PGs) are multi-potent mediators for local tissue homeostasis and inflammatory reactions. Addition of PGs to cultures of human skin fibroblasts led to a marked induction of the production of hepatocyte growth factor (HGF). PGE1 and PGI2 analogues were the most potent in stimulating HGF production by over 50-fold; PGE2 and PGD2 were less potent. Western immunoblotting of conditioned medium from skin fibroblasts indicated that both PGE1, PGE2, and PGI2 analogues specifically induce synthesis of HGF with a M(r) of 85,000, but not smaller variant of HGF with a M(r) of 28,000. Consistent with the induction of HGF production, steady-state expression of HGF mRNA in fibroblasts was strongly induced by PGE1 and PGI2 analogues, but slightly by PGE2 and PGD2, thereby indicating that PGs induce HGF production through transcriptional activation of the HGF gene. PGE1, PGE2, PGI2 analogue also stimulated HGF production in MRC-5 human embryonic lung fibroblasts and vascular smooth muscle cells. As dibutyryl cyclicAMP (dbcAMP) and tetradecanoylphorbol 13-acetate (TPA), but not Ca(2+)-ionophore A23187 stimulated HGF production in skin fibroblasts, activation of protein kinase-A and protein kinase-C may be coupled to the stimulation of HGF production. Simultaneous addition of PGE1 and TPA or dbcAMP and TPA led to a synergistic enhancement of HGF production, whereas the simultaneous addition of PGE1 and dbcAMP failed to additively enhance HGF production.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1995

Histamine activates bronchial epithelial cells to release inflammatory cytokines in vitro.

Airway epithelial cells have a potential to produce cytokines which are relevant to airway inflammation. To elucidate the mechanisms of their regulation, we focused on the effects of three chemical mediators [histamine, platelet-activating factor (PAF) and endothelin-1] important in the pathogenesis of bronchial asthma. Histamine, but not PAF or endothelin-1, showed a dose-dependent stimulatory effect on the release of interleukin-6, interleukin-8 and granulocyte-macrophage colony-stimulating factor by normal and transformed human bronchial epithelial cells when studied 6 h after the treatment. The process required protein synthesis as evaluated by the effect of cycloheximide, and was mainly via H1 receptor. We concluded that histamine might be involved in the activation of airway epithelial cells to release inflammatory cytokines in allergic responses.

Bronchi↗
PubMed1995

The analysis of p53 tumor suppressor gene in pineal parenchymal tumors.

p53 gene mutation was examined in 9 pineal parenchymal tumors, 4 pineoblastomas and 5 pineocytomas, by the immunohistochemical and the polymerase chain reaction-mediated single strand conformation polymorphism (PCR-SSCP) analyses. In each case, immunohistochemical analysis revealed no positive staining for p53 protein with either PAb1801 or DO-1 antibody and PCR-SSCP analysis revealed no abnormal migration in exons 5 to 8 of the p53 gene. These findings suggested that p53 gene mutation is rarely related with the tumorigenesis of pineal parenchymal tumors.

Adult↗
PubMed1995

[Effect of endogenous and inhaled nitric oxide on pulmonary microcirculation].

The sites of action of endogenous and inhaled nitric oxide (NO) were reassured during hypoxic pulmonary vasoconstriction. Lungs of 21 adult cats were perfused in situ with autologous blood in zone-3 conditions. Capillary pressures were measured by the double-occlusion techniques and pressures in arterioles and venules 70-100 microns in diameter were measured by the servo-null micropuncture technique, both during normoxia (FiO2 = 0.3) and during hypoxia (FiO2 = 0.02). The effects of NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), an inhibitor of NO synthase, and of inhaled NO (5-100 ppm) were also measured. The PO2 of the prefusate decreased from 187.6 +/- 5.3 mmHg during normoxia to 25.7 +/- 1.3 mmHg during hypoxia, and further decreased to 20.8 +/- 2.2 mmHg during hypoxia with 50 ppm NO (p < 0.05, compared with hypoxia only). Increases in pulmonary vascular pressure drop in response to hypoxia were 4.8 +/- 1.0 cmH2O and 9.1 +/- 1.4 cmH2O in non-treated and L-NAME-treated lungs, respectively (p < 0.05). L-NAME significantly increased hypoxic construction in the venous segment. The concentration of exhaled NO increased from 13 +/- 4 ppb during normoxia to 18 +/- 4 ppb during hypoxia (p < 0.1). Inhaled NO lowered not only pulmonary artery pressure but also capillary pressure in a dose-dependent manner, which reduced hypoxic pulmonary vasoconstriction. Pulmonary veins were more sensitive to inhaled NO than were arteries. Inhaled NO (50 ppm) dilated vessels smaller than 70 to 100 microns in diameter, by 39% (p < 0.05), and dilated venules greater than 100 microns in diameter by 26% (p < 0.05), but did not significantly dilate arterioles greater than 100 microns in diameter (11%). Inhaled NO did not significantly change the ratio of wet weight to dry weight. We conclude that both endogenous and inhaled NO attenuate hypoxic pulmonary vasoconstriction, with significant pulmonary venous dilation. The main site of action of inhaled NO is vessels smaller than 100 microns in diameter and venules greater than 100 microns in diameter. Inhaled NO (5-100 ppm) does not cause interstitial edema.

Administration, Inhalation↗
PubMed1995

[Pulmonary involvement of collagen vascular diseases: studies on prognostic factors from basic and clinical viewpoints].

In 715 patients with collagen vascular diseases, interstitial lung disease and pulmonary hypertension were found to be important causes of death (37.5% and 6%, respectively). The prognosis of interstitial lung disease associated with collagen vascular disease was better than that of idiopathic interstitial pneumonia; patients with the latter were more likely to experience exacerbations. A distinct subgroup of patients with dermatomyositis and interstitial lung disease with a rapidly progressive course was characterized by mild muscle symptoms, low levels of creatine phosphokinase and negative tests for anti-Jo-1 antibody. CT scores and analysis of bronchoalveolar lavage fluid proved to be of some value in predicting outcome. Measurement of IL-6 in bronchoalveolar lavage fluid and local immunostaining for this pro-inflammatory cytokine were helpful in evaluating responses to therapy.

Antibodies, Antinuclear↗
PubMed1994

Molecular cloning of a novel putative G protein-coupled receptor from rat aortic smooth muscle. Downregulation of the mRNA level by the cyclic AMP messenger pathway.

A cDNA clone encoding a novel putative G protein-coupled receptor was isolated from rat aortic vascular smooth muscle cell cDNA library by the polymerase chain reaction (PCR) using degenerate oligonucleotide primers and subsequent hybridization screening with a cloned PCR product. Sequence analysis of this clone (AGR9) shows that it encodes a 483 amino acid protein with seven streches of hydrophobic amino acids, which are presumed to represent transmembrane domains. In addition, AGR9 protein exhibits several structural features characteristic of the G protein-coupled receptor family, which include the existence of potential N-linked glycosylation sites in the amino-terminal region, phosphorylation sites by serine/threonine kinases in the intracellular regions, and a number of well-conserved residues among most of the G protein-coupled receptors. Northern blot analysis indicates abundant expression of a major 3.9 kb AGR9 mRNA in brain, lung, heart, stomach, intestine, cultured rat aortic smooth muscle cells and cardiac myocytes. Treatment of rat aortic smooth muscle cells with the adenylyl cyclase activator forskolin causes a marked and transient decrease in the steady-state level of AGR9 mRNA. Dibutyryl cyclic AMP and the beta-adrenergic agonist isoproterenol mimick the effect of forskolin. The ligand for AGR9 receptor has yet to be identified, however, these results suggest the existence of a novel G protein-coupled receptor expressed in the cardiovascular, central nervous and digestive systems.

Animals↗
PubMed1994

Partial purification and characterization of 'injurin-like' factor which stimulates production of hepatocyte growth factor.

We have previously reported the evidence for presence of a humoral factor 'injurin', which induces expression of the hepatocyte growth factor (HGF) gene in MRC-5 human embryonic lung fibroblasts. We have now purified a factor from porcine liver which stimulates HGF production but differs from injurin. When injurin activity was measured as a stimulatory effect on HGF production by MRC-5 cells, this activity was found in various acid extracts from porcine tissues, including liver, kidney, brain, and lung, and acid extracts from the liver was used for purification. When the acid extract was applied to Q-Sepharose anion-exchange chromatography, 50-60% of the total injurin activity was absorbed to the column and the remaining activity was detected in the flow through fractions. Injurin activity was eluted from the Q-Sepharose column by NaCl concentration gradient with four peaks at 0.5-0.6 M, 0.7-0.8 M, 0.9-1.2 M. 1.5-2.0 M NaCl, thereby suggesting that the factor exists in heterogenous or various forms in tissues. The major active fractions were combined and applied to Mono-Q FPLC anion-exchange chromatography. Injurin activity eluted with a single peak at 0.9-1.5 M NaCl and this activity was 4286 fold purified from the starting extract. Addition of this fraction to MRC-5 cells increased the amount of HGF pulse-labeled with [35S]methionine to a 3-4-fold higher level than that seen in control cells, whereas it had no significant effect on HGF mRNA levels. Therefore, this factor seems to stimulate HGF synthesis affecting translational processes and is distinct from the previously characterized injurin which stimulates HGF gene expression. Chemical treatments and SDS-polyacrylamide gel electrophoresis of this injurin-like factor indicated that injurin-like factor is a acid- and heat-stable non-proteinous factor with an apparent M(r) of 8-15 kDa. Since the injurin activity of the factor was decreased by heparinase treatment, the factor may be a polysulfated glycosaminoglycan related to heparin or to heparan sulfate. These results suggest that HGF production may be regulated by this non-proteinous injurin-like factor and that this factor may also play an important role in the regeneration of organs, through translationally enhancing HGF production.

3T3 Cells↗
PubMed1994

Suppression of neointimal smooth muscle cell accumulation in vivo by antisense cdc2 and cdk2 oligonucleotides in rat carotid artery.

Deendothelializing balloon injury of rat carotid artery results in progressive intimal smooth muscle cell accumulation and luminal stenosis over 14 days after injury. We have found transient rises (approximately 3-fold maximal increases over the uninjured control value) of the kinase activities of both cdc2 and cdk2, key molecules for cell cycle progression, in the injured carotid artery along with the development of intimal proliferation. The topical application of the antisense, but not the sense, cdc2 and cdk2 phosphorothioate oligodeoxynucleotides dissolved in F127 pluronic gel around the freshly injured artery resulted in reductions of the intimal smooth muscle cell accumulation by 47% and 55% respectively, as estimated by an intimal to medial cross-sectional area ratio, with concomitant decreases in cdc2 and cdk2 kinase activities. These results indicate that both cdc2 and cdk2 kinases are involved in intimal smooth muscle cell accumulation after balloon angioplasty and suggest a potential usefulness of the antisense cdc2 and cdk2 oligonucleotide therapy for arterial stenosis.

Angioplasty, Balloon↗
PubMed1994

Visualization of a moving quadrupole with magnetic measurements of peripheral nerve action fields.

Magnetic compound action fields (CAFs) over the right arm were measured from 63 sensor positions with two 7-channel SQUID gradiometer systems following electrical stimulation of the median nerve at the wrist. The field mapping of the CAFs revealed a propagating quadrupolar pattern with the leading depolarization and trailing repolarization fronts. The average distribution of the CAFs in the longitudinal direction was 9.0 cm in length for the depolarization field and 7.3 cm for the repolarization field in good agreement with a theoretical prediction based on the duration (3 msec) of the CAFs and the conduction velocity of the nerve (50 m/sec). The distance between the maxima of the depolarization front and the minima of the repolarization front was 6.3 cm. This spatial separation of the leading and trailing dipole locations suggests in part mutual cancellation of the fields with opposite polarity at or near the depolarized segment of nerve fibers.

Adult↗
PubMed1994

Effect of pulmonary blood flow on microvascular pressure profile determined by micropuncture in perfused cat lungs.

To clarify the role of the pulmonary microvasculature in adjusting to increased pulmonary blood flow, we measured arteriolar and venular pressure by the servo-null micropuncture method while changing the pulmonary blood flow in isolated perfused cat lungs. We divided the lung vasculature into three longitudinal segments: 1) arterial (pulmonary artery to 30- to 50-microns arteriole), 2) microvascular (between 30- to 50-microns arteriole and venule), and 3) venous (30- to 50-microns venule to left atrium). The vascular resistance was calculated by dividing the pressure gradient by the flow. The pressure gradient of the microvascular segment did not increase, whereas the pressure gradient of the arterial and venous segments increased simultaneously with flow rate. Total and microvascular resistance decreased with increase of flow rate. Resistances of the arterial and venous segments did not change with increase in flow. We conclude that the microvasculature plays a crucial role in preventing pulmonary hypertension with increases in flow by decreasing microvascular resistance.

Animals↗
PubMed1994

Angiographically occult vascular malformations: a correlative study of features on magnetic resonance imaging and histological examination.

With reference to vascular malformations, the term cavernous has architectural as well as histologic connotations. It refers to a compact pattern of growth wherein no intervening brain parenchyma is evident, as well as to the histological nature of the vessels, which are hyaline and collagenous in appearance, lacking the microscopic features of arteries or veins. Historically, cavernous angioma has been defined as exhibiting both features. Twenty-five patients with neurological symptoms and neuroimaging abnormalities who underwent surgery for cerebral vascular malformations between 1987 and 1990 satisfied the following study criteria: their lesions were angiographically occult and both magnetic resonance imaging (MRI) and histological sections were available for review. The patients' ages ranged from 4 to 49 years (mean, 30 years), the male to female ratio being 1:2. Two thirds of the lesions were supratentorial in location and all were intraparenchymal. All patients had clinical improvement after resection. In 24 of the 25 lesions, the vascular channels were histologically cavernous in nature; one inadequate specimen precluded classification. Three demonstrated a purely compact or cavernous pattern, 20 a mixed cavernous and racemose pattern, and one a purely racemose pattern. The authors conclude that 1) histologically cavernous lesions are the commonest form of occult vascular malformation; 2) a purely compact or cavernous architectural pattern is uncommon, most lesions showing a partially racemose architecture; 3) some histologically cavernous malformations possess a capillary component; 4) clinical growth of cavernous malformations may have its basis in intraluminal thrombosis and subsequent recanalization; 5) the T2-weighted MRI pattern of cavernous malformations varies, the most common being a multifocal hyperintense center surrounded by a hypointense ring; 6) the MRI pattern reflects the histological appearance; 7) since no thrombosed arteriovenous malformations were encountered, such lesions must be rare; 8) in that the pathophysiological hallmark of a cavernous lesion is recurrent thrombosis and hemorrhage, a resolving hematoma cannot always be distinguished from a cavernous lesion; 9) MRI is the examination of choice in evaluating occult vascular malformations; and 10) microsurgical excision is a satisfactory method of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1994

Pulmonary hypertension in systemic lupus erythematosus: a report of an autopsied case.

An autopsied case of systemic lupus erythematosus with pulmonary hypertension is reported. A 29-year-old woman with a seven-year history of polyarthralgia, butterfly rash, nephrotic syndrome and Raynaud's phenomenon was admitted because of progressive dyspnea on exertion. Tests for antinuclear antibody, anti-cardiolipin antibody and lupus anticoagulant were positive. Echocardiographic examination revealed right ventricular hypertrophy and a moderate pericardial effusion. Estimated systolic pulmonary arterial pressure was 53 mmHg. Despite treatment with corticosteroids including pulse methylprednisolone therapy, lipo-PGE1 and warfarin, she died of progressive congestive heart failure. Postmortem examination of the pulmonary vasculature revealed findings consistent with plexogenic pulmonary arteriopathy, without evidence of vasculitis, fibrinoid necrosis, or thromboemboli.

Adult↗