PubMed HealthSearch

Biomedical subjects

K Iwai

Publications and source records attributed to K Iwai.

At least 19 recordsLinked to original sources

A murine thymic stromal cell line which may support the differentiation of CD4-8- thymocytes into CD4+8- alpha beta T cell receptor positive T cells.

A fibroblastoid cell line TSt-4 was established from fetal thymus tissue of C57BL/6 mice. When fetal thymus (FT) cells or CD4-8- (DN) cells of adult thymuses were cultured on the monolayer of TSt-4, a considerable proportion of lymphocytes expressed CD4 or both CD4 and CD8 within 1 day, and the CD4+CD8- cells were maintained further while the CD4+8+ cells disappeared by Day 5. A large proportion of cells generated from DN cells but not FT cells was shown to express CD3 and T cell receptor alpha beta. Addition of recombinant interleukin (IL)-7 into the cultures resulted in a marked increase of cell recovery without virtual change in differentiation process of alpha beta lineage. The present work strongly suggests that thymic fibroblasts play an important role in T cell differentiation and IL-7 contributes to supporting proliferation of differentiated cells.

Animals

In vitro induction of IgG anti-DNA antibody from high density B cells of systemic lupus erythematosus patients by an HLA DR-restricted T cell clone.

An HLA-DR restricted T cell clone (26G11) which recognized a lymphoid cell-derived autoantigen associated with DR4 molecule was shown to induce not only autologous but also allogenic DR4+ B cells to produce large amounts of antibodies of the IgG and IgM classes. Using the helper activity of this clone, we investigated the mechanism of anti-DNA antibody production in DR-matched patients with systemic lupus erythematosus (SLE). When cultured with 26G11 cells, B cells from DR-matched normal control subjects produced large amounts of IgM anti-DNA antibody, but did not produce IgG anti-DNA antibody which is thought to have a pathological role in SLE. In contrast, B cells from DR-matched patients with active SLE spontaneously produced a fairly large amount of IgG anti-DNA antibody, and the production was augmented by the T cell clone. Little IgG anti-DNA antibody was produced by the B cells of patients with inactive SLE in either the presence or absence of T cell clone. We next fractionated B cells into low density B (LD-B) and high density B (HD-B) cells by centrifugation on discontinuous Percoll density gradients. IgG anti-DNA antibody was spontaneously produced by LD-B cells of active SLE patients but not by those either of inactive SLE patients or normal controls. On the other hand, although IgG anti-DNA antibody was not spontaneously produced by the HD-B cells of both active and inactive SLE patients, it could easily be induced by their culture with the T cell clone. Our results clearly show the existence of IgG anti-DNA antibody-producing B cells in the peripheral blood of SLE patients irrespective of their disease activity and suggest that autoreactive T cells may play a pathogenic role in SLE through the induction of autoantibody production.

Antibodies, Antinuclear

Superoxide dismutase enhances ischemia-induced reactive hyperemic flow and adenosine release in dogs. A role of 5'-nucleotidase activity.

To test the hypothesis that 5'-nucleotidase activity during ischemia is attenuated by oxygen-derived free radicals, we measured ischemia-induced reactive hyperemic flow, adenosine release, and 5'-nucleotidase activity in dogs (n = 62). A 1-minute occlusion of the coronary artery caused reactive hyperemic flow (307 +/- 5 versus 92 +/- 1 ml.100 g-1.min-1 at baseline) with increased release of adenosine (14.4 +/- 1.4 versus 0.4 +/- 0.1 nmol.100 g-1.min-1 at baseline). Superoxide dismutase augmented (p less than 0.001) both peak coronary blood flow (333 +/- 6 ml.100 g-1.min-1) and repayment (436 +/- 12 versus 320 +/- 7 ml/100 g in the untreated group). Adenosine release during reperfusion was augmented (22.7 +/- 1.9 nmol.100 g-1.min-1, p less than 0.001), and 8-phenyltheophylline completely abolished the enhanced reactive hyperemia. Enzymatic assay of 5'-nucleotidase activity revealed that the administration of superoxide dismutase increases ecto-5'-nucleotidase activity in ischemic myocardium. When an inhibitor of ecto-5'-nucleotidase, alpha, beta-methyleneadenosine 5'-diphosphate, was administered, the effects of superoxide dismutase were completely abolished. Thus, we conclude that 1) the augmentation of reactive hyperemic flow caused by superoxide dismutase is attributed to the enhanced release of adenosine and 2) the enhanced release of adenosine over the untreated controls is attributed to the protection of ecto-5'-nucleotidase activity during ischemia.

5'-Nucleotidase

Norepinephrine disrupts cytoskeletal framework of microtubules in rat hearts.

Sympathetic activations may deteriorate myocardial failure due to progression of myocardial cell injury. In the present study, to test whether microtubules, calcium ion (Ca2+) sensitive cytoskeletons, are disrupted by norepinephrine (NE) and whether beta-adrenoceptor antagonist could attenuate the disruption of microtubules, structures of microtubules are studied in rat hearts with continuous subcutaneous infusions of norepinephrine. In the sham operated rats the microtubules stained by immunohistochemical technique showed normal network structures. A low dose of NE infusion (2 micrograms/kg/h) for 6 h resulted in a minimal change in microtubule structures. However, infusion for 24 h of NE (2 micrograms/kg/h) and a large dose of NE infusion (20 micrograms/kg/h) for 6h caused disruptions of microtubules in small patchy lesions (8 +/- 3%, 12 +/- 4% of area, respectively). A large dose of NE infusion for 24 h increased systolic blood pressure from 116 +/- 6 to 152 +/- 4 mmHg and increased plasma NE concentration from 430 +/- 40 to 17100 +/- 3700 pg/ml and further disrupted the network of microtubules in 40 +/- 6% of the total area. Propranolol (500 micrograms/kg/h) markedly attenuated NE-induced disruptions of microtubules. Disruptions of microtubules may be one of the underlying mechanism of deterioration of myocardial failure in chronic heart failure in which sympathetic activity is markedly activated.

Animals

Disruption of microtubules in cultured neonatal rat cardiomyocytes during rapid contractions: protective effects of beta-adrenoceptor antagonist.

Tachycardia may play a key role in the progression of heart failure probably through Ca2+ overload. In the present study, to test whether microtubules, Ca(2+)-sensitive cytoskeletons, are disrupted by rapid contractions and whether the beta-adrenoceptor antagonist, propranolol could attenuate the disruption of microtubules, cultured neonatal rat cardiomyocytes with various contraction rates were studied. The microtubules were stained by immunohistochemical technique and the extent of microtubule disruption was quantified by disruption scores (grade 0-intact; grade 3-severe disruption). In 97% of the non-contracting cells, intact microtubules (grade 0) were observed, whereas in the cells that contract at the rate of 100-120/min, intact microtubules were observed only in 25% of the cells. The disruption scores were significantly correlated with contraction rates of the cells. Treatment with propranolol (10(-6)M) decreased the extent of microtubule disruption associated with a decrease in the contraction rate. However, this treatment did not alter the relationship between the contraction rate and the disruption score of microtubules. These results indicate that rapid contractions may induce disruption of microtubules which can be attenuated by beta-blocker mainly by its negative chronotropic effect. This may be one of the underlying mechanisms of the long-term effect of beta-blockers for chronic heart failure.

Animals

Sensitometric comparison of direct- and indirect-exposure films used in intraoral radiography.

In Japan, some dentists use indirect-exposure (screen) films for intraoral radiography, without the use of intensifying screens. The purpose of the present investigation was to determine whether film speed, inherent contrast, and latitude of Japanese indirect-exposure films used without intensifying screens were comparable to those of direct-exposure (non-screen) films used for intraoral radiography. The characteristic curves of Kodak Ektaspeed ("E" speed) and Ultra-speed ("D" speed) films were used as standards for comparison. Indirect-exposure films without intensifying screens were extremely slow compared with direct-exposure "E" and "D" speed films. Therefore, they should not be used for intraoral radiography because they needlessly expose the patient to excessive X-ray radiation. The direct-exposure films Hanshin Hi-Fi and Hanshin New Silver were equivalent in speed, higher in contrast, and narrower in latitude than Kodak Ektaspeed film. In general, the indirect-exposure films had lower speed, lower contrast and wider latitude than the direct-exposure films. Their speed and contrast would have been increased if intensifying screens had been used. Therefore, indirect-exposure films without intensifying screens should not be used for intraoral radiography.

Radiation Dosage

[Elemental analysis of hilar and mediastinal lymph nodes in idiopathic pulmonary fibrosis].

Elemental analysis of hilar and mediastinal lymph node tissues was performed to determine whether some inhaled atmospheric elements are implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). IPF was divided into two types; typical and atypical, according to our criteria. Lymph nodes were selected as the study material rather than lung tissue, because inhaled elements are concentrated in the hilar and mediastinal lymph nodes, and increase in lung weight due to fibrosis may influence the estimated values of element per unit weight of lung tissue. The hilar and mediastinal lymph nodes collected from 40 IPF cases and 43 non-IPF control cases were examined to determine the concentration of 13 elements in 100 mg dry tissue, using the X-ray fluorescent analysis method. For aluminium, 50 mg dry tissue was examined by an atomic absorption analysis method. Among the 14 elements, Ni in IPF lymph nodes showed a significantly higher level than in control nodes (mean +/- SD: 8.2 +/- 21.3 ppm versus 1.1 +/- 2.1 ppm, respectively. p < 0.01). No difference in each of the examined elements was noted between smokers and non-smokers or between typical and atypical IPF cases. Exogenous elements such as Ni may play a role as triggering substances in the pathogenesis of IPF.

Aged

[Clinico-pathological study of collagen-related pulmonary lesions in cases of open lung biopsy].

We studied the clinico-pathological correlation of collagen disease-related pulmonary lesions to examine the pathological and radiological features of collagen lung, and the effect of steroid therapy. Ten open lung biopsy cases were examined; 4 male, and 6 female. The mean age was 55 years old. Seven cases developed pulmonary shadows after the diagnosis of collagen disease, and 3 cases showed pulmonary shadow prior to diagnosis. Pathologically, 6 cases proved to be bronchiolitis obliterans organizing pneumonia (BOOP), 3 cases were chronic interstitial pneumonia (UIP), and 1 case was acute interstitial pneumonia. All cases had inflammatory thickening of the interstitium involving the pleura, bronchial wall, and perivascular connective tissue. Half of the cases had bronchiolar inflammatory lesions. Radiologically BOOP cases showed either localized ground glass shadows, or diffuse reticulonodular shadows predominantly in the lower lung fields with shrinkage of affected areas. UIP cases showed reticulonodular shadows, and active UIP cases showed overlapping ground glass shadows. Steroids were administered in cases of BOOP and active UIP, and all cases showed improvement. We consider that open lung biopsy is of use in the diagnosis of some cases and in assessing whether steroid therapy is indicated.

Aged

[A case of localized pleural mesothelioma containing a wedge-shaped area of aeration].

A 32-year-old man was admitted to our hospital because of an abnormal shadow on the chest X-ray film, which was detected on mass survey. The chest X-ray film on admission revealed an irregular mass shadow in the pleural layer between the left upper lobe and the lower lobe, and this shadow had a wedge-shaped area of aeration inside it. Needle biopsy under ultrasonography suggested a localized pleural mesothelioma. Surgery to resect the tumor revealed that it was pedunculated and had developed from the pleura of the left S5 segment. The resected specimen showed lung tissue invaginating into the tumor through a concave area of the tumor. The chest X-ray findings of this case are very unusual, and we were unable to find a similar case of localized pleural mesothelioma in the literature.

Adult

Qualitative difference of anti-DNA antibody-producing cell precursors in the pre-immune B cell repertoire between normal and lupus-prone mice.

The precursor frequency for anti-DNA antibody-producing cells in the pre-immune B cell repertoire was investigated in young female BALB/c and NZW mice, and in young and aged female NZB x NZWF1 (B/WF1) mice. Spleen cells from these mice were diluted serially and stimulated polyclonally in vitro with lipopolysaccharide (LPS) and IL-4 to induce both IgM and IgG1 production. The results demonstrated that there existed virtually no difference in precursor frequency for IgM anti-DNA antibody-producing cells between normal and lupus mice, confirming previous observations made by other investigators. In contrast, the number of precursors for IgG1 anti-DNA antibody-producing cells was much higher in young and old B/WF1 mice than in normal mice. These results suggest that the high frequency of precursors for IgG1 anti-DNA antibody-producing cells in the pre-immune B cell repertoire of B/WF1 mice is a crucial factor for the pathogenesis of systemic lupus erythematosus.

Animals

Role of increased alpha 1-adrenergic activity in cardiomyopathic Syrian hamster.

We investigated serial changes in myocardial norepinephrine content and myocardial adrenergic receptors during the development of cardiomyopathy in Syrian hamsters (Bio 14.6) and their age-matched healthy controls. We also examined phosphatidylinositide hydrolysis after alpha 1-adrenergic stimulation and the effects of alpha 1-blockade. We found that in the prehypertrophic stage, myocardial norepinephrine content and densities of alpha 1- and beta-adrenergic receptors were significantly higher in the cardiomyopathic hamsters than in the controls. However, in the early heart failure stage, beta-receptor density was 28% lower than that of the age-matched controls, although alpha 1-receptor density remained 55% higher. Norepinephrine-stimulated phosphatidylinositide hydrolysis in the cardiomyopathic hamster in the hypertrophic stage was twice that in the controls, indicating that the increase in alpha 1-adrenergic receptors is coupled with the intracellular signal transduction. Furthermore, selective alpha 1-adrenoceptor blockade by bunazosin in the cardiomyopathic hamsters from 70 to 170 days of age reduced myocardial hypertrophy and focal myocardial necrosis. Thus we conclude that increased alpha 1-adrenergic activity plays an important role in progression of cardiac hypertrophy is cardiomyopathic Syrian hamsters.

Adrenergic alpha-Antagonists

Role of oxygen-derived free radicals in myocardial edema and ischemia in coronary microvascular embolization.

BACKGROUND: Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization. METHODS AND RESULTS: To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization. CONCLUSIONS: We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization.

Allopurinol

Excess death of lung cancer among sarcoidosis patients.

This study is to calculate a risk of lung cancer in a cohort of 1411 sarcoidosis cases which were followed for a 3 year period from 1984 to 1987. The physicians were requested to answer the questionnaire about progress of the disease by mail. Excess death was investigated using standardized mortality ratio (SMR). The expected number of deaths was calculated from Japanese sex-age specific mortality rate in 1985, using person-year method. Death from all causes and cancers did not show any excess. SMR being 0.98 and 0.97 respectively. The SMR of lung cancer was 3.26 (male: 5.56, female: 3.03), being statistically significant. The SMR of lung infection was 4.2, with statistical significance. The SMR of other main causes of death in Japan i.e., cerebrovascular accident, ischemic heart diseases and heart failure was less than 0.88. It is probably that sarcoidosis is a risk factor of lung cancer. The SMR of leukemia and uterine cancer was 5.88 and 8.70, respectively, though the observed number of leukemia was too small to conclude how high the cancer risk is among sarcoidosis patients. Gastric cancer, hepatic cancer and colon cancers were not observed.

Adult

[Standardization of definitions concerning smoking behavior among Japanese adolescents--results from the Japan Adolescent Smoking Survey (JASS)].

The aim of the Japan Adolescent Smoking Survey (JASS) is to standardize the definitions of smoking behavior among Japanese adolescents together with measurement methods and questionnaires concerned. A study of 9921 school children aged 9 to 18 years in 17 elementary schools, 16 junior high schools and 18 senior high schools in 9 prefectures, was conducted between June and July of 1989, to determine the relationship between actual smoking behavior during the past month or year and the "self-referent label" concerning their smoking status. The main results were as follows: 1) The percentage of those who smoked at least one cigarette during the past month showed a high degree of similarity to the percentage of those who referred to themselves as "regular smokers" or "occasional smokers". 2) Less than 10% of students who identified themselves as "never smokers" or "ex-smokers" smoked at least one cigarette during the past month, while more than 80% of students who referred to themselves as "regular smokers" or "occasional smokers" smoked during the past month. 3) On the whole, those who smoked 20 or more cigarettes during the past month referred to themselves as "regular smokers"; those who smoked between 2 and 19 cigarettes as "occasional smokers"; those who smoked 1 cigarette as "ex-smokers"; those who did not smoke during the past month as "never smokers". 4) The definition where students who smoked one cigarette during the past month are classified as a category of smoker, displayed a high level of sensitivity and specificity for all school-level groups and for both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent