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S Kira

Publications and source records attributed to S Kira.

At least 55 records · Page 3Linked to original sources
PubMed1996

Altered vasoreactivity in lungs isolated from rats exposed to nitric oxide gas.

A rebound phenomenon (severe arterial desaturation and pulmonary vasoconstriction) has been observed in some patients with pulmonary hypertension after sudden discontinuation of nitric oxide (NO) inhalation therapy. The mechanism responsible for this phenomenon is unknown. It has recently been reported that NO synthase (NOS) can be inhibited by NO as a negative feedback mechanism. We therefore hypothesized that this rebound phenomenon might be attributable to reduced endogenous NO production due to inhibition of pulmonary endothelial NOS (eNOS) activity by inhaled NO. To test this hypothesis, vasoreactivities were compared in isolated perfused lungs from rats exposed to 40 ppm NO gas and room air for 2 days. The pressor responses to angiotensin II and hypoxia of lungs from rats exposed to NO were markedly potentiated and their depressor response to bradykinin was considerably impaired, whereas that to sodium nitroprusside was preserved, compared with the responses of those exposed to room air. This altered pulmonary vasoreactivity was also induced by lower concentrations of inhaled NO (as low as 1 ppm) and was completely reversed by discontinuation of NO inhalation for several (< 8) hours. The expression of eNOS mRNA by lungs isolated from rats exposed to 40 ppm NO and room air for 2 days did not differ. These results suggest that pulmonary endogenous NO production is reversibly reduced after relatively short-term NO inhalation, which probably inhibits eNOS activity directly. We speculate that reduced production of pulmonary endogenous NO by exogenous (inhaled) NO could be the mechanism responsible for this rebound phenomenon.

Administration, Inhalation↗
PubMed1996

Prognostic value of Ia+ T lymphocytes in bronchoalveolar lavage fluid in pulmonary sarcoidosis.

We investigated the value of the la+ T-lymphocyte (CD3+ HLA-DR+) ratio in bronchoalveolar lavage fluid (BALF) for predicting the outcome of pulmonary sarcoidosis. Analysis of the BALF la+ T% in 166 patients with pulmonary sarcoidosis by dual-color flow cytometry revealed a wide range of values, of from 0.5 to 85.3%. Although the majority of patients had less than 40% la+ T cells in their BALF, a minor peak was observed at 50 to 60%. The BALF la+ T% value was not influenced by smoking, sex, or age, thus differing from other BALF activation markers. Fifty patients could be followed up precisely for 3 yr after their initial bronchoalveolar lavage (BAL) to evaluate outcome with respect to chest X-ray findings, clinical symptoms, serum angiotensin converting enzyme (ACE) activity, and extrapulmonary involvement. The 50 patients were divided into two groups, with a BALF la+ T% < 40% (n = 34) and > or = 40% (n = 16), respectively. Serum ACE activity returned to normal within 1 yr in the < 40% group, but remained high for the entire follow-up period in the > or = 40% group. The significant difference was observed in the persistence of pulmonary involvement between the two groups except for four patients who showed Stage 0 disease (p < 0.02). Thirteen of 31 patients in the < 40% group showed normalization of chest X-ray findings after three years, whereas only one out of 15 patients in the > or = 40% group showed resolution of pulmonary involvement. Our results suggest that the BALF la+ T% may be a novel marker for predicting the long-term prognosis in pulmonary sarcoidosis.

Adolescent↗
PubMed1996

Diffuse progressive pulmonary interstitial and intra-alveolar cholesterol granulomas in childhood.

We describe an 18 year old male with pulmonary interstitial and intra-alveolar cholesterol granulomas (PICG), which developed to severe respiratory failure over 15 yrs. The histological diagnosis was made on the basis of open lung biopsy findings at the age of 3 yrs and autopsy at 18 yrs of age. Although the pathological features of the lung were similar to that of paediatric patients with lipoid pneumonia coexisting with pulmonary alveolar proteinosis (PAP), gastro-oesophageal reflux (GOR) and a diverse group of severe primary diseases, the patient lacked evidence for any of these. We believe the present case provides a new example of a diffuse-type of lipoid pneumonia coexisting with pulmonary alveolar proteinosis, which we call cholesterol granulomas.

Adolescent↗
PubMed1996

[Introduction of molecular biology in respiratory medicine and its perspective].

I reviewed the change of respiratory medicine in the past several decades, overlapping with my own history of medical training and clinical and research works. In the 1950's when I graduated from the medical school and internship, the tuberculosis had been conquered effectively by the development of new antituberculous agents and improvement of nutritional state in Japan. Fibroptic bronchoscopy was introduced in the respiratory medicine in 1968, and computed tomography, in the 1970's, which gave us a good insight into pathological and biological aspects of various lung diseases in vivo. Molecular biology was brought in the respiratory medicine and our laboratory in the last decade, and my colleagues used it for genetic study of hereditary diseases such as alpha-1 antitrypsin deficiency and protein C deficiency, biochemical analysis of lung cancer and other pulmonary diseases, rapid detection of microorganisms, and so on. In the next step, gene therapy will come true in the near future, and I hope many intractable diseases such as lung cancer and interstitial pneumonia will be cured by the new technology and scientific knowledge.

Humans↗
PubMed1996

[Transfer of endothelial nitric oxide synthase gene in the purpose of gene therapy for pulmonary arterial hypertension].

Nitric oxide (NO) is a messenger molecule involved in diverse processes in many tissues. For example, NO is responsible for the bactericidal activities of macrophages, and in blood vessels it accounts for endothelium-derived relaxing factor activity. Recently, inhalation of NO gas was reported to improve the acute pulmonary arterial hypertension. Based on this knowledge, recombinant expression of endothelial nitric oxide synthase (eNOS) in lung may have profound effects on pulmonary vasomotor function and pulmonary arterial smooth muscle proliferation and platelet adhesion. On the basis of this concept, we evaluate the feasibility of gene therapy for chronic pulmonary arterial hypertension using hypoxia regulatable adenoviral vector coding eNOS cDNA.

Animals↗
PubMed1996

[Alpha 1-antitrypsin deficiency in Japan].

Alpha 1-antitrypsin (alpha 1-AT) deficiency is very rare in Japan although it is one of the most common hereditary disorders in Caucasians. Only 12 cases of alpha 1-AT deficiency have been reported in Japan. Their genetic abnormalities have already elucidated in 10 cases: Mnichinan, a heterozyge of Mmalton, 7 unrelated cases of Siiyama, and a case of 14q-syndrome. The Siiyama is the first prevalent deficient variant in the race other than the Caucasian race. The Siiyama mutation occurred on the normal alpha 1-AT variant M1 (Val213) which seems to be evolutionally newer than M1 (Ala213) on which the Z type mutation occurred. The result that alanine residue was not detected at 213 amino acid position in alpha 1-AT genes of 193 Japanese volunteers may be the reason why genetically proved Z deficient variant have not been reported yet in Japan.

Amino Acid Sequence↗
PubMed1996

[Pulmonary eosinophilic granuloma with relatively rapid progression and remission].

A 53-year-old woman with a smoking history of 20 pack-years was admitted to the hospital because of dry coughing and exertional dyspnea that had progressed over the previous 3 months. A chest X-ray film taken one month before the onset of symptoms was almost normal. Diffuse small nodular shadows with infiltration were evident one month after the onset of symptoms, and increased rapidly until admission to the hospital. Eosinophilic granuloma was diagnosed histologically after thoracoscopy. The symptoms, chest X-ray findings and pulmonary-function data improved spontaneously after admission to the hospital and the nodular shadows had a almost completely disappeared by 5 months later; the patient continued to smoke. The present case is unique and valuable because it shows the natural course of eosinophilic granuloma from the onset of symptoms to remission.

Eosinophilic Granuloma↗
PubMed1996

[Pulmonary cavernous hemangioma--identification of its endothelial cell origin by immunohistological staining].

A 45-year-old woman was referred to our hospital because of a tumorous shadow in the S10 segment of the left lung. A chest computed tomography (CT) scan showed a nodular lesion with a slightly irregular margin and no contrast enhancement. CT-guided aspiration biopsy was tried but did not result in a histological diagnosis. The tumor was excised during video-assisted thoracoscopic surgery. Histological examination of the specimen revealed cavernous hemangioma. Most cells lining the lumen of the cavernous structure stained positively for von Willebrand factor antibody and negatively for anti-epithelial membrane antigen antibody, which suggests that the tumor was associated with endothelium. To the best of our knowledge, this is the first report of a case in which the diagnosis of pulmonary cavernous hemangioma was confirmed with an immunohistological study.

Antibodies↗
PubMed1995

Structural organization of pulmonary arteries in the rat lung.

The structure of the normal pulmonary arteries in the rat was studied with light and electron microscopy after use of a newly devised technique of perfusion fixation and tissue preparation. We distinguished two main types of artery in the rat lung on the basis of the structure of the media, an elastic artery and a muscular artery. The elastic artery was characterized by an abundance of extracellular matrix in the media and by an oblique arrangement of smooth muscle cells to connect neighboring elastic laminae. It was subdivided into two segments, a classical elastic and a transitional elastic segment. The muscular artery was distinguished by a paucity of extracellular matrix in the media and by a circumferential arrangement of smooth muscle cells (or pericytes) enclosing the lumina, and was subdivided into four segments, a thick muscular, an ordinary muscular, a partially muscular and a nonmuscular segment. The smooth muscle cells in the muscular artery contained well-developed microfilament bundles compared with those in the elastic artery. Structural differences in smooth muscle cells and in extracellular matrix in the media between the elastic and muscular arteries may reflect the functional heterogeneity of pulmonary arteries in response to hypoxic pulmonary vasoconstriction and to vasoactive substances such as endothelium-derived relaxing and hyperpolarizing factors, and endothelin.

Actin Cytoskeleton↗
PubMed1995

Effect of cigarette smoke on the mRNA and protein expression of carcinoembryonic antigen (CEA), a possible chemoattractant for neutrophils in human bronchioloalveolar tissues.

BACKGROUND: The concentration of carcinoembryonic antigen (CEA), known as a marker of malignant transformation and chronic inflammation, is increased in bronchoalveolar lavage fluid obtained from smokers compared with fluid from non-smokers. This study investigated the mechanism and biological significance of CEA production in the lungs of smokers by evaluating protein and mRNA expression in non-carcinomatous lung parenchymal tissues and in cell lines derived from human fetal lung. METHODS: Lung parenchymal tissue free from cancer or an inflammatory lesion was obtained from five non-smokers (four with lung cancer, one with pulmonary mycetoma), five ex-smokers (all with lung cancer except for one with mesothelioma), and 14 smokers (nine with lung cancer, five with emphysema) at surgery or necropsy. Cancer tissue was also collected simultaneously from the subjects with lung cancer. CEA protein in the tissue homogenates was measured by enzyme linked immunoassay. CEA mRNA expression in the non-carcinomatous parenchymal tissue and cancer tissue was evaluated by in situ hybridisation using CEA specific riboprobe and was semiquantitated by counting the number of silver grains per cell. CEA mRNA expression was also compared in three cell lines derived from human fetal lung (IMR-90, MRC-9, and CCD-14Br) after in vitro stimulation with medium exposed to cigarette smoke or air. Chemoattractant activity of purified CEA for neutrophils and monocytes was also studied in vitro. RESULTS: CEA content in non-carcinomatous lung tissue was increased in smokers with emphysema (mean (SD) 38.0 (9.2) ng/mg protein) or with lung cancer (38.2 (21.6)) compared with non-smokers (11.0 (5.4)) or ex-smokers (5.9 (2.2)). CEA mRNA expression in non-carcinomatous tissue, expressed by average number of grains per cell, was also increased in smokers with emphysema (mean (SD) 11.2 (4.1)) or with lung cancer (14.0 (8.4)) compared with non-smokers (3.1 (0.6)) or ex-smokers (4.0 (1.7)). CEA content in carcinomatous tissues was 42.8 (37.3) for non-smokers, 38.2 (42.4)) for ex-smokers, and 59.0 (22.5) for smokers. The CEA content in carcinomatous tissue was higher than in non-carcinomatous tissue, but there was no difference between non-smokers, ex-smokers, and smokers. The numbers of grains per cell in carcinomatous tissue were higher than in non-carcinomatous tissues, but not different among non-smokers (30.3 (3.9)), ex-smokers (38.3 (13.8)), and smokers (44.3 (5.2)). CEA mRNA expression in the cell lines was upregulated after the incubation with smoke-treated medium. Purified CEA was chemoattractant for neutrophils but not for monocytes in vitro. CONCLUSIONS: mRNA and protein expression of CEA were increased in the normal lung tissue from smokers compared with non-smokers or ex-smokers. Since CEA content and mRNA expression were no different between smokers with non-small cell lung cancer and those with non-carcinomatous disease, it is unlikely that CEA expression in non-carcinomatous lung parenchymal tissue was influenced by the presence of the tumour and is consistent with the effect of smoking. This is supported by in vitro studies which show that cigarette smoke could induce CEA mRNA expression in fetal lung derived cells. In addition, CEA might play a part in recruitment of neutrophils into the lower respiratory tract.

Aged↗
PubMed1995

Effects of separate and combined ETA and ETB blockade on ET-1-induced constriction in perfused rat lungs.

To evaluate the role of endothelin (ET) receptors in ET-1-induced pulmonary vasoreactivity, we studied the effects of ET-receptor agonists and antagonists in isolated perfused rat lungs. ET-1 (1-10 nM) caused concentration-dependent pulmonary vasoconstriction and gross pulmonary edema at a concentration of 10 nM. The combination of the selective ETA antagonist BQ-123 and the selective ETB antagonist BQ-788 inhibited ET-1-induced pulmonary vasoconstriction more effectively than BQ-123 alone, whereas BQ-788 alone enhanced the constriction. ET-1-induced hydrostatic pulmonary edema was prevented by the combination of BQ-123 and BQ-788 but not by either BQ-123 or BQ-788 alone. After the addition of 125 ng of exogenous ET-1, the perfusate levels of ET-1 were significantly higher in BQ-788-treated lungs than in either the vehicle control or BQ-123-treated lungs. The selective ETB agonist IRL-1620 also caused pulmonary vasoconstriction and edema, both of which were completely inhibited by BQ-788. ET-1-induced transient vasodilation was abolished by BQ-788 but was unaffected by BQ-123. These results suggest that in the isolated perfused rat lung, ET-1-induced vasoconstriction is mediated by both ETA and ETB receptors, whereas ET-1-induced transient vasodilation is mediated exclusively by the ETB receptor. Blockade of ETB receptors may result in enhanced ET-1 activity (via the ETA receptor) through inhibition of the ETB-mediated clearance of ET-1. Thus combined ETA and ETB blockade is required for the complete inhibition of ET-1-induced vasoconstriction in the rat pulmonary circulation.

Animals↗
PubMed1995

Gender effect on prognosis of patients receiving long-term home oxygen therapy. The Respiratory Failure Research Group in Japan.

Although long-term home oxygen therapy (LTOT) certainly prolongs survival, it is not known whether this advantageous effect is similar for both sexes. In this study, we analyzed sex-related differences in survival based on a very large population that had received LTOT from 1986 to 1993. A total of 9,759 patients with chronic obstructive pulmonary disease (COPD), sequelae of tuberculosis (TBsq), and chronic interstitial pneumonia (IP) were selected in 1,212 medical institutions for analysis of survival rates. The survival rates of both sexes were compared with each other using the Cutler-Ederer Method. Despite higher PaCO2 at the beginning, the survival rate of women was significantly better than that of men in these three disease categories. Cox's proportional hazards analysis further confirmed the gender effect on survival by eliminating the effects of age, PaO2, PaCO2, %VC, and FEV1/FVC. The mean survival periods of the women who died during follow-up periods were also significantly longer than those of men (0.41 yr in COPD, 1.84 yr in TBsq, and 0.78 yr in IP). From these findings, we conclude women have a better prognosis than men when they start receiving LTOT, regardless of the cause of respiratory failure.

Female↗
PubMed1995

Localization of platelet-derived growth factor and insulin-like growth factor I in the fibrotic lung.

To better understand the mechanisms responsible for the increase in numbers of fibroblasts and increased collagen synthesis in fibrotic intestitial lung diseases, platelet-derived growth factor (PDGF)-A and PDGF-B, PDGF receptor-alpha and -beta, insulin-like growth factor I (IGF-I), and IGF-I receptor were evaluated immunohistochemically. Additionally, the messenger ribonucleic acids (mRNAs) for PDGF-A and PDGF-B, PDGF receptor-alpha and -beta, and IGF-I were investigated by in situ hybridization in alveolar macrophages and lung tissues from patients with interstitial lung disease. In specimens of bronchoalveolar lavage fluid (BALF), PDGF-A, PDGF-B, and IGF-I were local in alveolar macrophages in patients with idiopathic pulmonary fibrosis (IPF), patients with sarcoidosis (Sar), and normal individuals. Although there were no differences between IPF and Sar in terms of the staining intensity or number of positive cells, the number of such cells was smaller in the normal controls. In lung tissues with early-stage IPF, PDGF and IGF-I proteins were localized exclusively in alveolar macrophages, mononuclear phagocytes, fibroblasts, alveolar Type II cells, vascular endothelial cells, and vascular smooth-muscle cells. In lung tissues with late-stage IPF and those from normal controls, only alveolar macrophages contained PDGF and IGF-I proteins. Interestingly, the cellular localizations of PDGF receptor-alpha and -beta, and of IGF-I receptor were the same as those of the PDGF and IGF-I proteins in early-stage IPF, whereas these cells were not positive for any of these substances in late-stage IPF or normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Alpha 1-antitrypsin-deficient variant Siiyama (Ser53[TCC] to Phe53[TTC]) is prevalent in Japan. Status of alpha 1-antitrypsin deficiency in Japan.

In contrast to the fact that alpha 1-antitrypsin (alpha 1-AT) deficiency is one of the most common hereditary disorders of Caucasians, deficient variants among Orientals have been recognized to be extremely rare. Only 12 cases of alpha 1-AT deficiency have been reported in Japan, including five cases in which the genetic defects have already been elucidated: Mnichinan (delta Phe52[TTC] and Gly148[GGG]-->Arg148[AGG]), two unrelated cases of Siiyama (Ser53[TCC]-->Phe53[TTC]), a heterozygote of Mmalton (delta Phe52[TTC]), and one additional case of 14q- syndrome (sporadic deletion of the neighboring region of the alpha 1-AT gene locus). alpha 1-AT Siiyama is a deficient variant originally identified in a 38-yr-old patient with pulmonary emphysema in Japan. The amino acid substitution in this variant occurs in a highly conserved residue of the serpin (serine protease inhibitor) backbone (Seyama K, et al. 1991. J. Biol. Chem. 266:12627-12632). We attempted to determine whether alpha 1-AT deficiency in Japan was caused by independent genetic defects or whether it shared some common mutations in the alpha 1-AT gene. We examined five of seven available families for which the genetic defects causing alpha 1-AT deficiency have not yet been explored. When the allele-specific polymerase chain reaction (PCR) was performed with a pair of oligonucleotide primers having the mutated base sequence of the alpha 1-AT Siiyama allele at the 3' end, all eight cases of alpha 1-AT deficiency among five unrelated families turned out to be homozygous carriers of the alpha 1-AT Siiyama mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

An adult case of lymphangiomatosis of the mediastinum, pulmonary interstitium and retroperitoneum complicated by chronic disseminated intravascular coagulation.

Pulmonary lymphangiomatosis is a rare clinical and pathological entity which is distinct from lymphangiomyomatosis and from pulmonary lymphangiectasis. We report a case of a 20 year old man with diffuse lymphangiomatosis involving the mediastinum, lungs and retroperitoneum. The patient's intrathoracic lymphangiomatosis produced restrictive and obstructive impairment of his pulmonary function, but did not result in chylothorax or chylopericardium, which are two common manifestations of the disease. The patient's clinical course was remarkable for the concomitant development of chronic disseminated intravascular coagulation (DIC). Lymphangiomatosis involving both the mediastinum and pulmonary parenchyma is rare, and DIC is a very unusual complication of lymphangiomatosis.

Adult↗