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Biomedical subjects

T Wada

Publications and source records attributed to T Wada.

At least 523 records · Page 29Linked to original sources

Identification of S-phase cells with PC10 antibody to proliferating cell nuclear antigen (PCNA) by flow cytometric analysis.

We estimated the expression of proliferating cell nuclear antigen (PCNA) in HeLa S3 cells by flow cytometry with monoclonal antibody (MAb) PC10. HeLa cells were fixed with six different fixation procedures: 15-min and 30-min acetone, 15-min acetone followed by 15-min methanol (acetone/methanol), 30-min methanol, 15-min methanol followed by 15-min acetone (methanol/acetone), and a mixture of acetone and methanol. The fixed cells were applied to MAb PC10 against PCNA and then treated with FITC. With five fixation procedures except for acetone/methanol, PCNA was expressed in almost all cells with similar shapes and different FITC intensity levels on PCNA/DNA bivariate cytograms, whereas acetone/methanol fixation allowed PCNA detection in S-phase cells with a cytogram that showed a horseshoe-like pattern with a peak level at mid-S-phase. Flow cytometric dual parameter analysis of PCNA/BrdU was carried out in HeLa cells to confirm detection of PCNA in S-phase cells with acetone/methanol fixation. The population of cells stained for both parameters, i.e., S-phase cells, was obviously discriminated from that of the non-S-phase cell in PCNA/BrdU bivariate cytograms. These results strongly suggest that PCNA used with acetone/methanol fixation would be equal to BrdU as an S-phase marker.

Antibodies, Monoclonal↗

Age-dependent decreases in fibrinolytic enzyme activities in serum of healthy subjects.

We investigated the age-dependency of serum levels of 9 kinds of proteases. The results showed that the enzymatic activities corresponding to urokinase, plasmin, and thrombin, all involved in blood clotting and fibrinolysis, were inversely correlated with age. This suggests that there is some similarity between the normal process of aging and the pathologic process of Alzheimer's disease. Compared with our previous data on Alzheimer patients, the present results indicate that some derangement in the aging process is involved in the pathogenetic mechanisms of Alzheimer's disease.

Aging↗

[Nonpeptide angiotensin II-receptor antagonists].

The renin-angiotensin system (RAS) is known to play a very important role in cardiovascular diseases. The present state of the research on orally active nonpeptide angiotensin II (A II)-receptor antagonists and their pharmacological characterization will be reviewed. In the late 1970s, the first nonpeptide A II-receptor antagonists were discovered among some derivatives of imidazoleacetic acid, and this was followed by the development of losartan in 1989. TCV-116, synthesized in our laboratories, is a prodrug that is converted in vivo to the active form CV-11974. TCV-116 and CV-11974 were demonstrated to be effective antagonists for many A II-induced cardiovascular actions and are effective antihypertensive agents in several animal models of hypertension. TCV-116 also demonstrated secondary benefits in treating congestive heart failure (CHF), preventing stroke, delaying the progression of renal disease and preventing the intimal thickening of vascular injury in animal models. Clinical studies confirmed the efficacy of TCV-116 in the treatment of essential hypertension. The utility of A II antagonist may extend beyond that of hypertension and CHF, as suggested by the potential usefulness of ACE inhibitors in the treatment or prevention of many other cardiovascular diseases. The A II antagonists will help to determine the role of the RAS in the physiologic regulation and in the pathophysiology of various cardiovascular diseases.

Angiotensin Receptor Antagonists↗

Effects of Ca channel agonists on 45Ca uptake differ depending on the state of NG108-15 cells.

We investigated the effects of various Ca channel agonists (Ca agonist) derived from 1,4-dihydropyridine on KCl-stimulated 45Ca uptake by differentiated and undifferentiated neuroblastoma x glioma hybrid NG108-15 cells with and without dibutyryl cAMP. Ca agonists Bay K 8644, YC-170 and CGP 28392 enhanced KCl-stimulated 45Ca uptake in differentiated NG108-15 cells, but only slightly in undifferentiated NG108-15 cells. The rank order of the enhancing effects was roughly Bay K 8644 > YC-170 > > CGP 28392. These results suggest that there is some difference between the mechanism by which these Ca agonists affect KCl-stimulated 45Ca uptake in differentiated and undifferentiated NG108-15 cells, although the nature of that difference is not clear.

Bucladesine↗

Statistical characterization of negative control data in the Ames Salmonella/microsome test.

A statistical characterization of negative control data in the Ames Salmonella/microsome reverse mutation test was performed using data obtained at Takeda Analytical Research Laboratories during January 1989 to April 1990. The lot-to-lot variability of bacterial stock cultures and day-to-day variability of experiments were small for Salmonella typhimurium strains TA1535 and TA1537 and Escherichia coli WP2uvrA, but they were larger for S. typhimurium TA100. The number of revertant colonies for all test strains studied here followed Poisson distributions within the same day. The two-fold rule that is an empirical method to evaluate the Ames Salmonella/microsome test results has been widely used in Japan. This two-fold rule was evaluated statistically. The comparison-wise type I error rate was less than 0.05 for TA98, TA100, TA1535, TA1537, and WP2uvrA. Moreover, this rule is particularly conservative for TA100, for which the type I error rate was nearly 0.

Analysis of Variance↗

Chick production by in vitro fertilization of the fowl ovum.

The aim of this study was to produce viable chicks by in vitro fertilization and transfer of fertilized ova to the oviduct of recipient hens. Out of a total of 76 transferred ova, 53 were laid with fully calcified shells, 31 of which were fertile (58%). Despite the high rate of embryonic loss, six live chicks were hatched from 12 fertile ova exposed to 0.05 ml of semen (1:200 dilution). Nine healthy chicks were hatched from ten control ova which were recovered from the oviduct following artificial insemination and subsequent transfer to recipient hens. This experimental approach provides a useful model for production of transgenic chicks.

Animals↗

Trilineage response to rhG-CSF with subsequent clonal hematopoiesis in a patient with severe bone marrow aplasia.

We treated a patient with severe aplastic anemia with long-term administration of recombinant human granulocyte-colony stimulating factor (rhG-CSF). When a trilineage response of hematopoiesis was obtained after the first treatment, a chromosomal change [45XX, -7] was observed in 20 of the 20 metaphases examined. Later, we were able to show a monoclonal X inactivation pattern in the phosphoglycerate kinase (PGK) gene in the peripheral blood polymorphonuclear leukocytes and mononuclear cells, indicating the presence of clonal hematopoiesis regardless of the disappearance of the karyotype abnormality. We suggest that it is important to pay close attention to the appearance of clonal hematopoiesis during the administration of G-CSF to patients with idiopathic severe bone marrow aplasia.

Adult↗

[Longitudinal change in independence in the elderly--Kahoku Longitudinal Aging Study (KLAS)].

A community based study named Kahoku Longitudinal Aging Study (KLAS) was conducted since 1990 for the purpose of evaluating the comprehensive geriatric functional assessment (CGA) and preventing a decline in CGA in the community-dwelling elderly population. It was carried out in a Japanese rural town, in which 32% of the population was over 65 years of age. This study included a questionnaire about activity of daily living (ADL), information-related physical function, mental (cognitive and affective) and social functional domains. In addition to subjective informative instruments, various types of objective assessment such as quantitative neuro-behavioral function tests and medical examinations were performed. Subjects were all the eligible elderly aged over 65 years in the community. Although the ratio of subjects who were independent in ADL decreased with advancing age in both 1991 and 1993, the ratio of the independent elderly in ADL became significant higher (74%) in 1993 than in 1991 (71%). Scores on 2 kinds of neurobehavioral function tests in the 159 subjects aged over 75 years who attended the examination every year showed a significant and slight decrease during two years. However, some test indices significantly improved during the 2 years. These results suggested that age-related dependency in ADL and some kind of neurobehavioral functions might be prevented, in part, by health promoting education and improvement of life style.

Activities of Daily Living↗

[Comparative study of activity of daily living in the elderly between in Kahoku and in Yaku].

A comparative community-based study of physical activity in the elderly was carried out between two Japanese rural towns, Kahoku and Yaku. This study included a questionnaire about activity of daily living (ADL) and information-related functions in relation to lifestyle. Subjects were all the eligible elderly aged over 65 years of each community (1618 and 704 subjects in Kahoku and Yaku respectively). The ratio of the eligible elderly aged over 65 years were 32% in Kahoku and 2% in Yaku. The response rates were 91% in Kahoku and 51% in Yaku. Common findings in both towns were as below; 1) scores in ADL decreased with advancing age, 2) information-related functions were similar in each town, and between genders, 3) marital condition among males was similar in both towns, 4) ADL scores were higher in the financially rich group than in the poor one, 5) ADL scores were higher in female subjects whose husbands were alive than in widows, 6) ADL scores were higher in subjects who walked every day than those who did not, 7) ADL scores were lower in subjects who took medicine every day than those who did not, however, this finding did not apply to antihypertensive drugs, 8) ADL scores were higher in subjects who drank in beverages than in those who never imbibed. The different results between Kahoku and Yaku were supposed to be due to differences in lifestyle.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

[Comparative study of blood pressure variability in the elderly in Kahoku and in Yaku].

A comparative community-based study of blood pressure (BP) variability in the elderly was carried out in the Japanese rural towns of Kahoku and Yaku. The prevalence of hypertension, orthostatic hypotension and use of antihypertensive drugs, effects of postute on BP and the "white coat" effect in BP were examined in each town. There was no difference in the prevalence of hypertension between in the two towns. Orthostatic increase in BP and pulse rate was more common in elderly females than in elderly males in both towns, indicating that standing itself was a load for subjects and activated sympathetic nervous tone in the female elderly. The prevalence of orthostatic hypotension was 8.5% and 12% in Kahoku and Yaku respectively, and the "white coat" effect on BP was demonstrated in the elderly in each town. In conclusion, we should take orthostatic change and the "white coat" effect into consideration in the evaluation of BP among the elderly.

Aged↗

[Comparative study of serum lipids and other blood chemistry factors in the elderly in Kahoku and Yaku].

A comparative community-based study of serum lipids and other blood chemistry data in the elderly was carried out in two Japanese rural towns, Kahoku and Yaku. We studied the following blood chemistry factors; total proteins (TP), albumin (Alb), blood glucose (glucose), urea nitrogen (BUN), uric acid (UA), total cholesterol (T-Cho), high density lipoprotein (HDL-C) and lipoprotein (a) (Lp(a)). Subjects were the 312 eligible elderly aged over 75 years in Kahoku, and 172 similar elderly in Yaku. There were no significant differences in TP, Alb, glucose, BUN and UA of the elderly in the two areas. Mean HDL-C level was significantly lower and mean Lp(a) concentration was significantly higher in the elderly in Kahoku than in Yaku, Mean value of T-Cho did not differ significantly between the elderly in the two areas, however, the ratio of subjects whose T-Cho concentrations were over 220 mg/dl was significantly higher in Kahoku than in Yaku. These data suggested that the risk of atherosclerosis from the standpoint of view of serum lipids was higher in the elderly in Kahoku than in those in Yaku. Epidemiological data of Kochi and Kagoshima prefecture indicated that the mortality ratio from ischemic heart disease was higher in Kahoku than in Yaku, although that from cerebral infarction was lower in Kahoku than in Yaku. Comparative study of laboratory data in various districts is useful to investigate the relationship between lifestyle and diseases.

Aged↗

[Comparative study of neurobehavioral function in the elderly between in Kahoku and Yaku].

A comparative study of neurobehavioral functions in the elderly was carried out between two Japanese rural towns, Kahoku and in Yaku. To evaluate of neurobehavioral functions, we used 1) Mini Mental State Examination (MMS), 2) Hasegawa Dementia Scale Revised (HDSR), 3) Kohs block design test, 4) Visuospatial cognitive performance score (VCPS), 5) Button Score (Button-S), 6) Up & Go test, and 7) Functional reach (FR). A questionnaire about ADL, information-related function and lifestyle was also done. Subjects consisted of all the eligible 332 elderly aged over 75 in Kahoku and 194 elderly aged over 75 in Yaku. In Kahoku, each function test had a significant correlation with age. However, in Yaku, the Up & Go, FR, MMS and HDSR results showed no significant correlation with age. Scores in cognitive function tests such as MMS, VCPS, and the Kohs test were better in kahoku than in Yaku, although scores in behavioral function tests such as FR were better in Yaku than in Kahoku. MMS, HDSR and Kohs tests significantly correlated with information-related function while Button-S, Up Go and FR tests had significant correlation one with ADL in both areas. Scores on function tests were better in the living-alone group and the group who had a daily work than in other groups in Kahoku. However, differences in scores in function tests between these two types of groups failed to reach a level of significance in Yaku. These data suggested that the difference in life-style influenced neurobehavioral functions in the elderly.

Activities of Daily Living↗

[Comparative study of quality of life in the elderly between in Kahoku and in Yaku].

A comparative community-based study of quality of life (QOL) in the elderly was carried out between two Japanese rural towns, Kahoku and Yaku.QOL, which included the subjective sense of health, appetite, sleep at night, mood, memory, family relationships, friendship, economic condition, life satisfaction and happiness was assessed using a visual analogue scale (VAS) as well a Geriatric depression Scale (GDS), a variety of neurobehavioral function tests, and a questionnaire about activity of daily living (ADL). Subjects were all the eligible elderly aged over 75 years in both communities. Inter-rater reproducibility in VSA was more reliable than that in GDS. Life satisfaction and a subjective sense of happiness highly correlated with mood, family relationships, friendship and economic condition. GDS and VAS significantly correlated with family relationships, active participation in a group and economic condition, however, they did not correlated with age. The subjective sense of happiness correlated with ADL and steadiness of walk as assessed by neurobehavioral function tests. Living style correlated with VAS in the male elderly, but not female. Each score in VAS for family relationships, friendship, economic condition, life satisfaction and subjective sense of happiness was significantly higher in the elderly in Yaku than in Kohoku. The diseases which elderly people wanted to avoid were dimentia cancer, stroke, and cardiovascular disease in that order. In conclusion, QOL in the elderly population was influenced by disease, neurobehavioral functions, especially walking function, gender difference, lifestyle as well as cultural environment.

Activities of Daily Living↗

Low-molecular-size allergens, LM-1s, in feces extract of Dermatophagoides farinae which elicit histamine release from washed blood cells of patients with bronchial asthma.

A significant activity to elicit histamine release was found in an ultrafilterable (Mr-cutoff < 10 kD) fraction of a mite feces extract from a spent mite medium. The activity was divided into two fractions (LM1 and LM2) on an Ultrogel AcA 54 column when monitored by histamine release assay using washed peripheral blood cells from mite-allergic patients. The larger-molecular-size antigen, LM1 was further separated into three allergenic fractions by consecutive chromatography on Sephadex G-50, GM-DEAE, and TSKgel ODS-120T. All the purified allergens, LM1s (LM1a, LM1b, and LM1c), which produced positive reactions in skin tests on allergic patients, were glycoproteins (molecular weight: 8 kD on SDS-PAGE; 12.5 kD on Gel filtration) with different carbohydrate contents and pI values ranging from 4 to 5 on an IEF plate. LM1s were cross-reactive with anti-Der f II but not with anti-Der f I. The reaction of LM1c to anti-Der f II serum was completely inhibited with the other antigens, while the reactions of LM1a and LM1b to the serum were partially inhibited with LM1c or the other antigens, respectively.

Allergens↗

A low-molecular-size LM2 allergen in mite, Dermatophagoides farinae, extracts containing feces which elicits conjunctival reactions in patients with bronchial asthma.

A low-molecular-size antigen, LM2, which possesses a significant activity to elicit histamine release, was isolated from an ultrafilterable (Mr-cutoff < 10k) fraction of a mite extract containing feces by consecutive chromatography on Ultrogel AcA 54 and Sephadex G-25. The isolated antigen was still heterogeneous glycoproteins, giving a smeary band around pI 3-5 on an Ampholine PAG plate, with molecular weights of 6-8k and 4k on SDS-PAGE and Sephadex G-50 gel filtration, respectively. Chemical treatments of the antigen suggested that the epitope responsible for the elicitation of histamine release resided in the protein moiety. The antigen had activities to provoke conjunctival congestion and histamine release in mite-allergic patients, but not immunogenicity by itself. The antigen competitively inhibited the reactions of HM1, HM2, and HM3 fractions to corresponding antisera, but did not cross-react with anti-Der f I or anti-Der f II sera.

Allergens↗

[A case of ANCA-associated rapidly progressive glomerulonephritis with oral aphtha and erythema nodosum].

We reported a case of a 22-year old female with a microscopic form of polyarteritis nodosa (PN) who initially manifested Behçet's disease-like symptoms, such as fever, arthralgia, oral aphtha and erythema nodosum, and rapidly progressive glomerulonephritis (RPGN). On admission, her urinalysis showed active nephritic syndrome and her renal function rapidly deteriorated; serum creatinine levels elevated from 1.2 to 3.9 mg/dl within 2 weeks. Skin biopsy specimens from erythema showed panniculitis. Accordingly, she was treated with daily 30 mg of oral prednisolone and three-day intravenous pulse therapy of 1000 mg of methylprednisolone twice. After treatment, skin eruption and oral aphtha disappeared, and the serum creatinine level improved to 1.2 mg/dl. Percutaneous renal biopsy performed on the 28th day showed focal necrotizing glomerulonephritis and hyalinosis of small arteries. Immunofluorescence studies showed only trace stainings for IgG, IgA and beta lc. Electron microscopic findings revealed fusion of the foot process and swelling of endothelial cells, but no dense deposits. Anti-neutrophil cytoplasmic antibody (ANCA) was positive for IgG class with a 40-fold titer by indirect immunofluorescence test and showed a cytoplasmic pattern combined with high urinary IL-8 level (280.1 pg/ml). We diagnosed this case as a microscopic form of PN. ANCA titer and urinary IL-8 correlated positively with the disease activity, and were finally below 8-fold and 58.6 pg/ml, respectively after resolution of RPGN for 42 months. In this case, ANCA was useful not only for differential diagnosis of the patients with systemic vasculitis and crescentic glomerulonephritis, but also for evaluation of the disease activity.

Adult↗

[A case report of allergic granulomatous angitis with the perforation of ileum].

A case of allergic granulomatous angitis (AGA) complicated with the perforation of the ileum was described. A 52-year-old male had suffered from bronchial asthma since 1990, and two years later he had severe attack of asthma and manifestation of systemic vasculitis. He was diagnosed a AGA with the symptom of vascultitis, history of asthma, and the abnormal hematological findings (WBC 13000/mm3, eosinophilia 11.1%, IgE 1290U/ml, RA 2+). The treatment with adrenal corticoid hormone was started. In April 1992, he complained of severe right lower abdominal pain. He was diagnosed the gastrointestinal perforation by the abdominal X-ray examination and emergency operation was performed. Two ileal perforations were found at the operation and the ileectomy was carried out. Only 11 cases of AGA complicated with the gastrointestinal perforation have ever been reported in Japan. The perforation occurred often at the small intestine and the poor prognosis was referred. The administration of adrenal corticoid hormone should be continued after operation.

Humans↗