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Biomedical subjects

S Kira

Publications and source records attributed to S Kira.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Cardiac sarcoidosis with myopathy and advanced A-V nodal block in a woman with a previous diagnosis of sarcoidosis].

In 1992, a 49-year-old woman was admitted to the hospital because of exertional dyspnea. Three years earlier sarcoidosis had been diagnosed, and the patient was found to have bilateral hilar lymphadenopathy. The eye, skin, and knee joint were also involved. During the second hospital stay, atrial flutter with advanced A-V nodal block, scattered defects on a 201T1 scintigram, and marked cardiomegaly on chest roentgenogram led to the diagnosis of cardiac sarcoidosis. Signs and symptoms of cardiac failure subsided after placement of an artificial cardiac pacemaker, but the patient still complained of mild muscle weakness in the lower extremities on exertion. 67Ga scintigraphy revealed marked accumulation in the lower extremities, and muscle biopsy of the left gastrocnemius revealed numerous epithelioid cell granulomas with muscle fiber degeneration. Oral corticosteroid therapy was effective. A review of the 24 cases of sarcoid myopathy reported in Japan indicated that the male-to-female ratio is 1:3.8. As compared to patients in whom myopathy led to the diagnosis of sarcoidosis, those in whom myopathy developed after sarcoidosis was diagnosed were (1) relatively older, (2) more likely to have multiple organ involvement, and (3) more likely to have cardiac sarcoidosis. Corticosteroids were beneficial in about three quarters of these 16 cases, who received corticosteroid therapy.

Anti-Inflammatory Agents↗
PubMed1994

Amylase mRNA transcripts in normal tissues and neoplasms: the implication of different expressions of amylase isogenes.

To understand the cellular origin and mechanism of gene expression in amylase-producing cancers, the phenotyping of amylase isogenes by the polymerase chain reaction and restriction-fragment-length polymorphism using restriction endonucleases TaqI, DdeI, HinfI, and AfaI were performed for 3 amylase-producing lung adenocarcinomas, 16 lung cancers without hyperamylasemia, other human malignant neoplasms, cultured cell lines, and normal tissues. In addition, amylase mRNA transcripts were semi-quantified by the limited polymerase chain reaction. Amylase mRNA transcripts were detected in all of the tissues examined. The AMY1 gene (salivary type) was exclusively and highly expressed in the salivary glands and the amylase-producing lung adenocarcinomas. Coexpression of the AMY1 gene and AMY2 gene (pancreatic type) was observed in most of the lung cancers without hyperamylasemia, lung tissue, and cells scraped from the tracheal epithelium, thyroid, and female genital tract (ovary, fallopian tube, and uterus cervix), while minimal levels of mRNA transcripts of the AMY2 gene were detected in other malignant neoplasms, various normal tissues, and the cultured cell lines. All mRNA transcripts identified as being those of the AMY2 gene were further identified as being from the AMY2B gene except for the transcripts from the pancreas, in which the AMY2A gene and AMY2B gene were coexpressed. On the basis of these results, the clinical occurrence of amylase-producing cancer likely relates to the tissues expressing the AMY1 gene, while the AMY2B gene, which evolutionarily is the oldest gene among human amylase isogenes, is constitutively expressed in various tissues.

Amylases↗
PubMed1994

Ubiquitous presence of mutagenic and antimutagenic components in air-borne particulates of two Japanese cities.

Previous studies on several samples of urban air-borne particulates showed that the long-chain fatty acids present in these samples can interfere with the measurement of mutagenicity of the particulates with the Salmonella assay. To explore whether this phenomenon is a general, fatty acid contents and the mutagenicity (with Salmonella typhimurium TA98 without S9) were measured for 34 particulate samples collected in the cities of Okayama and Tokyo over a period of 1 year. Palmitic, stearic, oleic and linoleic acids were found in all these samples in this order of amount, and their interference on mutagenicity measurement was eminent, particularly at high doses of the sample. With the use of blue cotton extraction, the mutagenic components can be freed from most of these antimutagenic factors. Significant correlation was found between the number of particulates and the mutagenicity per unit volume of the air. Eight polycyclic aromatic hydrocarbon compounds, including benzo[alpha]pyrene were quantified for these 34 particulate samples. Their contents were too small to account for the observed mutagenicity, suggesting that other polycyclic compounds, possibly involving nitro aromatics, were responsible for the mutagenicity observed. No remarkable differences were noted between Okayama and Tokyo in fatty acid contents, mutagenicity or polycyclic aromatic-hydrocarbon contents of the samples.

Air Pollutants↗
PubMed1994

Biliary glycoprotein mRNA expression is increased in primary lung cancer, especially in squamous cell carcinoma.

Biliary glycoprotein (BGP), a member of the carcinoembryonic antigen gene family, is a cell surface glycoprotein that has both a transmembrane domain and a cytoplasmic domain. BGPs consist of at least four isoforms (BGPa, b, c, and d) and function in vitro as Ca(2+)-dependent homotypic intercellular adhesion molecules. The mRNA expression of BGP gene was investigated in specimens of primary and metastatic cancer tissues from 15 patients with primary lung cancer (six squamous cell carcinomas, five adenocarcinomas, and four small cell carcinomas). The specimens were also compared with normal adjacent tissues of the same individuals with squamous cell carcinoma. BGP mRNA expression was increased in carcinomatous tissues of the primary site, especially in squamous cell carcinoma, but was not detected in adjacent normal tissues by Northern blot analysis or in situ hybridization. Interestingly, BGP mRNA expression was apparently decreased in metastatic lesions compared with the primary site in the six individuals with squamous cell carcinoma. Furthermore, a loss of BGPa isoform was observed by reverse transcriptase-polymerase chain reaction in four of six patients with squamous cell carcinoma. These results suggest that the reduction of BGP expression may play an important role in the process of metastasis through decreasing adhesive interactions with surrounding cells, especially in squamous cell carcinoma.

Adenocarcinoma↗
PubMed1994

Clinical significance of necrosis in lupus nephritis.

The significance of necrosis (karyorrhexis), among the most characteristic findings in lupus nephritis, was evaluated by studying the correlation between the existence of necrosis in renal biopsy specimens and laboratory findings. The subjects were 54 patients with diffuse proliferative lupus nephritis and 6 patients with focal proliferative lupus nephritis selected from 143 patients with lupus nephritis. We also compared the clinical course of oral prednisolone and intravenous methylprednisolone pulse therapies after steroid administration. Compared with the non-necrosis group, the necrosis group had significantly lower CH50 levels and more proteinuria. Patients with necrosis were effectively treated with repeated pulse therapy judging by immunological activity and the decrease in proteinuria at an early stage, but responded poorly to oral steroid therapy. As the presence of necrosis in cases of lupus nephritis means high immunological activity of the lesion and there is responsiveness to a large dose of steroids, extensive immunosuppressive therapy including methylprednisolone pulse therapy should be applied to these patients.

Administration, Oral↗
PubMed1994

[Research on the pulmonary circulation--from physiology to molecular biology].

After more than 30 years of research and clinical work, I would like to review the past and offer advice to young doctors. I began my research career with physiological studies of the pulmonary microcirculation. Then, based on concepts derived from those studies, I extended my work by doing clinical studies of pulmonary vascular diseases. My young coworkers are now breeding rats to be used as models of pulmonary hypertension. We are doing physiological and pathological studies of these animals, and we have taken on the challenge of treating them with the techniques of molecular biology. The extension of my research over these past 30 short years has been extremely rapid and comprehensive. Reflecting on the path of my research, I offer the following lessons. The directions in which my work has taken me have been unpredictable. New knowledge and techniques have, of course, been important, but so has my contact and collaboration with coworkers and senior colleagues, both in Japan and abroad. The pace of scientific research is increasing. I advise you to be flexible and accepting of new knowledge, and not to adhere to the traditional limits on the scope of clinical, physiological, and pathological research.

Animals↗
PubMed1994

[Gene transfer to airway epithelial cells: current status and future direction].

Advances in recombinant DNA technology and molecular and cellular biology have made it feasible to introduce genes into living cells. The most sophisticated gene transduction methods have bee applied to gene therapy strategies for the potential treatment of genetic diseases. In regard to lung diseases, alpha 1-antitrypsin deficiency and cystic fibrosis, the most common hereditary lung disorders in Caucasians, have been targeted for gene therapy. To date, gene therapy studies have been confined to ex vivo strategies for treatment of ADA deficiency with retroviral vectors. However, there are two major obstacles to gene transfer to the bronchial epithelium. First, bronchial epithelium, such as that with ciliated cells, is terminally differentiated, and does not divide rapidly. Second, the complex architecture of the lung precludes replacing the existing bronchial epithelium with cells modified by gene transfer. In the context of these properties of bronchial epithelium, adenovirus vectors have been evaluated for direct introduction of therapeutic genes to bronchial epithelium via the airway in vivo. An in vivo experiment revealed that gene transfer with a replication-deficient adenovirus containing the E. coli lacZ (beta-galactosidase) gene driven by cytomegalovirus promoter (AdCMVlacZ) was 10(4) times more efficient than gene transfer with a plasmid containing the same expression cassette (pCMVlacZ). An experiment based on in vitro data was done to evaluate the distribution of the expression of the exogenous genes transferred by adenovirus vectors. Intratracheal administration of AdCMVlacZ into lungs of experimental animals resulted in a high number of beta-gal-positive epithelial cells in bronchiols, rather than in proximal bronchi. Thus, a replication-deficient adenovirus can be used to transfer exogenous genes to airway epithelial cells in vivo. This technique may be useful in gene therapy for cystic fibrosis. Gene transfer can be thought of as the use of genetic information to modity the milieu of the target organ. In addition, gene transfer may allow the introduction of new genes, or the alteration tion of existing genes in intact animals. Gene transfer could them be used to produce animal models of human lung diseases that are particularly difficult to study.

Animals↗
PubMed1994

[The gamma delta T-cell receptors in sarcoidosis].

T-cells recognize specific antigen (s) through the T-cell antigen receptors (TCR). gamma delta T-cells compose a minor population of the peripheral blood lymphocytes (PBL). These lymphocytes play a central role in recognizing the mycobacterial antigens and granuloma formation in tuberculosis and leprosy. Significant increase of gamma delta T-cells in PBL is observed in a subgroup of sarcoidosis. The majority of gamma delta T-cells showed V gamma 9/V delta 2 recombination, which is common in normal blood. To evaluate the clonality of the increased gamma delta T-cells in PBL, several V gamma 9 and V delta 2 cDNA clones were established. Analysis of V-J junctional sequences of V gamma 9 clones revealed oligoclonal expansion in some cases. Most of V delta 2 clones showed unique sequences. Although no clonal expansion of gamma delta T-cells were observed, TCR-gamma chain might recognize limited numbers of putative antigens in sarcoidosis.

Amino Acid Sequence↗
PubMed1994

[Retroviral infection as a putative pathogen for sarcoidosis].

Sarcoidosis is a granulomatous disorder of unknown etiology. Accumulated data suggest that one or several exogenous or altered self antigens participate in producing pathophysiological change in sarcoidosis. Recently, analysis of retroviruses such as HTLV-1 and HIV-1 revealed that these viruses would produce autoimmune disease like symptoms including interstitial lung disease like pulmonary manifestation. We hypothesized novel type retrovirus or retrovirus related antigens might be a putative pathogen for sarcoidosis. Syncytial cell formation or cytopathic effect was observed in 6 of 24 patients (25%) after coculture of sarcoid BALF cells with U937 cells. Five of 18 culture supernatant showed moderate reverse transcriptase activity. Expression of clone 4-1 env protein, one of the endogenous retroviral elements, was also observed in alveolar macrophages of sarcoidosis. These data encourages the further investigation of retrovirus as the pathogen of sarcoidosis.

Adult↗
PubMed1993

The assessment of proliferating cell nuclear antigen immunohistochemical staining in small hepatocellular carcinoma and its relationship to histologic characteristics and prognosis.

BACKGROUND: A precise prognostic factor for small hepatocellular carcinoma (HCC), the diagnosis of which recently has increased in incidence because of the development of diagnostic imaging techniques, is desirable. It has been reported that proliferating cell nuclear antigen (PCNA) would be related to proliferating cells, and thus the PCNA labeling index may provide useful information about the biologic behavior of small HCC. METHODS: An assessment was made of proliferative activity by immunohistochemical staining using a monoclonal antibody against PCNA in 46 nodules of HCC less than 3 cm in diameter resected from 44 patients. A correlation between PCNA labeling index and clinicopathologic findings or prognosis was sought. RESULTS: The mean labeling index was 18.7% in HCC and 1.9% in nontumor liver tissue. The labeling index corresponded to the degree of histologic differentiation, and the labeling index of well differentiated HCC was significantly lower (P < 0.05) than that of moderately or poorly differentiated HCC. The incidence of capsule formation in the high labeling index group (labeling index > or = 20%) was significantly higher (P < 0.05) than that in the low labeling index group (labeling index < 20%). A high incidence of capsular and vascular invasion was found in the high labeling index group. The survival rate after resection was significantly higher (P < 0.05) and the recurrence rate significantly lower (P < 0.05) in the low labeling index group than in the high labeling index group. CONCLUSIONS: The PCNA labeling index was shown to be closely related to histologic characteristics, and proved to be a useful indicator of recurrence and survival in small HCC.

Adult↗
PubMed1993

The lung in polyarteritis nodosa: a pathologic study of 10 cases.

Polyarteritis nodosa (PAN) is characterized by necrotizing arteritis of medium-sized and small arteries in various organs. Pulmonary artery involvement in PAN has been considered rare. Previously, it also has been thought that patients with PAN do not have interstitial pneumonitis and fibrosis. A detailed pathologic analysis of pulmonary diseases associated with PAN was made in 10 autopsy cases of PAN. Arteritis affecting bronchial arteries was present in seven patients (70%). The data obtained suggest that arteritis in the lung in patients with PAN is more common than has been recognized previously. Diffuse alveolar damage (DAD) involving all lobes bilaterally was present in five patients; it was acute in two patients and organizing in three. In the patients with organizing DAD the degree of fibrosis in the interstitium differed among the lobes, and the fibrosis was more severe in the lower lobe than in the other lobes. Two patients presented with interstitial fibrosis with honeycomb lung of the posterior and lateral basal segments of the lower lobes of both lungs; in one of these patients interstitial fibrosis was present in an area of organizing DAD. Five patients died of respiratory failure resulting from DAD. In conclusion, it is important to consider DAD and interstitial fibrosis as complications of PAN.

Adolescent↗
PubMed1993

Cathepsin L activity is increased in alveolar macrophages and bronchoalveolar lavage fluid of smokers.

Elastinolytic enzymes derived from alveolar macrophages (AM) are considered to play an important role in the development of emphysema associated with cigarette smoking. In this study, the enzyme activity and mRNA expression of cathepsin L were quantitated in AM and bronchoalveolar lavage (BAL) fluid obtained from current smokers and compared with those from nonsmokers. Activity was measured with the synthetic substrate Z-Phe-Arg-MCA combined with a novel cathepsin B inhibitor, CA-074. We found that the specific activity of cathepsin L was significantly elevated in BAL cells from smokers (7.1 +/- 0.7 mumol/mg protein/h, mean +/- SEM) compared with cells from nonsmokers (2.9 +/- 0.3) (p < 0.01). The expression of cathepsin L mRNA in BAL cells as determined by dot-blot analysis was also higher in BAL cells from smokers, which was comparable to the increase in the enzyme activity. About 5 to 6% of the specific activity of cathepsin L in BAL cell lysates was detected in unconcentrated BAL fluid; specific activity was also significantly higher in samples from smokers (0.38 +/- 0.04 mumol/mg protein/h) than from nonsmokers (0.14 +/- 0.02). In addition, procathepsin L (42 kD) and the mature form of cathepsin L (33 kD) were demonstrated in BAL fluid by immunoblot analyses. These data suggest that cigarette smoking induces mRNA expression and the synthesis of cathepsin L in AM and the release of procathepsin from AM into extracellular milieu. Furthermore, increased activity levels of cathepsin L in extracellular compartments may contribute to the proteolysis of elastin in the process of lung destruction associated with cigarette smoking.

Adult↗
PubMed1993

Massive chest wall tumor diagnosed as Askin tumor. Successful treatment by intensive combined modality therapy in an adult.

A 24-year-old woman was admitted due to dyspnea on exertion. A chest roentgenogram revealed a massive tumor originating from the right anterior chest wall when pleural effusion was drained. Diagnosis of Askin tumor was made based on light microscopic findings characterized by composing with small round cells, immunocytochemical findings suggestive of neuroectodermal origin, and cytogenetic analysis demonstrating the chromosomal translocation (11; 22). After intensive combined modality therapy, including chemotherapy, irradiation, and additional surgery, she was followed up as an outpatient and has remained disease-free for 16 months after initial diagnosis.

Adult↗