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Biomedical subjects

R Aoki

Publications and source records attributed to R Aoki.

At least 55 records · Page 3Linked to original sources

Epidemiology of diseases of unknown etiology, specified as "intractable diseases".

In Japan, epidemiological studies on intractable diseases have been undertaken and greatly promoted for more than 20 years by the Research Committee on Epidemiology of Intractable Diseases, with the financial supports from the Ministry of Health and Welfare of Japan. In this paper, chronological history of development of the Research Committee and some scientific accomplishments by the recent Research Committee (1993-1995) were summarized, mainly focusing on descriptive, analytical and other epidemiological studies. Hoped is that the readers are to be acquainted with the recent research activities by the Research Committee and seek for possible international collaborations in epidemiological studies on intractable diseases.

Epidemiologic Methods↗

Expression and purification of the light chain of botulinum neurotoxin A: a single mutation abolishes its cleavage of SNAP-25 and neurotoxicity after reconstitution with the heavy chain.

Botulinum neurotoxin type A (BoNT/A) selectively and irreversibly inhibits acetylcholine release from peripheral nerve endings. While the toxin's heavy (H) chain contributes to neuronal binding and internalization, its light (L) chain is a Zn(2+)-dependent endoprotease that intracellularly cleaves synaptosomal-associated protein of M(r) = 25 kDa (SNAP-25). For research and clinical exploitation of this uniquely-acting neurotoxin, recombinant wild-type L chain was produced together with a mutant in which His227 in the Zn(2+)-binding motif was substituted by Tyr. The PCR-amplified wild-type and mutant L chain genes were cloned, fused to the gene for maltose-binding protein, and expressed at high levels in Escherichia coli. The soluble fusion proteins were purified using amylose affinity chromatography, and, after factor Xa cleavage, the free L chains were isolated. The wild-type was shown to proteolyze SNAP-25 at a rate approaching that of the native chain while the mutant was inactive. Reconstitution of the pure wild-type L chain with native homogeneous H chain yielded a disulfide-linked dichain form that inhibited neuromuscular transmission in vitro and produced the symptoms of botulism in vivo. After reconstitution with the H chain, the Tyr227 mutant L chain failed to show any neuroparalytic activity in either of these assays. This methodology allows, for the first time, routine preparation of recombinant forms of the L chain that are needed to decipher the molecular details of its interaction with substrate and, thereby, assist the design of effective inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP-Binding Cassette Transporters↗

Epidemiology of breast cancer in Japan.

BACKGROUND: A recent increase in the numbers of deaths and incident cases of breast cancer among Japanese women stimulated the authors to summarize the trends in female breast cancer mortality and incidence rates in Japan. METHODS: The number of deaths from female breast cancer was obtained from the national vital statistics. Estimated incidence rates, based on several cancer registries, were also used for the analyses. The trends in the age-adjusted and age-specific rates were examined. Age and birth cohort effects on the incidence and mortality rates were examined, using multiplicative models. RESULTS: The age-adjusted mortality rate has been increasing since the 1960s (4.1 per 100,000 population in 1950 and 6.6 in 1991, adjusted by the World Population). The age-adjusted incidence rate has also been rising since 1975. Age-specific rates have been increasing particularly in the age range 40-79 years. The multiplicative models disclosed an increasing cohort effect for the mortality and incidence rates among women born after 1900. Decreasing mortality and incidence rates after menopause were ascribed by the models to strong cohort effects. CONCLUSIONS: The recently increasing trend was believed to be consistent with changed risk factors among Japanese women. The age effect on female breast cancer incidence rate in Japan was concluded to be similar to that in Western populations.

Adult↗

Tea consumption and lung cancer risk: a case-control study in Okinawa, Japan.

To disclose the relationship between tea consumption and lung cancer risk, we analyzed the data from a case-control study conducted in Okinawa, Japan from 1988 to 1991. The analysis, based on 333 cases and 666 age-, sex- and residence-matched controls, provided the following major findings. (a) The greater the intake of Okinawa tea (a partially fermented tea), the smaller the risk, particularly in women. For females, the odds ratios (and 95% confidence intervals) for those who consumed 1-4, 5-9, and 10 cups or more of Okinawan tea every day, relative to non-daily tea drinkers, were 0.77 (0.28-2.13), 0.77 (0.26-2.25) and 0.38 (0.12-1.18), respectively (trend: P = 0.032). The corresponding odds ratios for males were 0.85 (0.45-1.55), 0.85 (0.45-1.56) and 0.57 (0.31-1.06) (trend: P = 0.053). (b) The risk reduction by Okinawan tea consumption was detected mainly in squamous cell carcinoma. Daily tea consumption significantly decreased the risk of squamous cell carcinoma in males and females, the odds ratios being 0.50 (95% confidence interval 0.27-0.93) and 0.08 (0.01-0.68), respectively. These findings suggest a protective effect of tea consumption against lung cancer in humans.

Adenocarcinoma↗

Significance of urinalysis for subsequent kidney and urinary tract disorders in mass screening of adults.

To evaluate dipstick urinalysis as a predictor of subsequent kidney and urinary tract disorders in apparently healthy adults, we designed a cross-sectional, prospective, and retrospective study within a cohort. The severity of proteinuria was significantly (p < 0.01) associated with the amount of pathological casts, whereas hematuria without proteinuria was not. The frequency of subsequent serum creatinine increase (0.3 mg/dl/5 years or more) was significantly enhanced (from 0.4% to 7.3% along with the severity of proteinuria, whereas it was not related to the severity of hematuria. Patients who subsequently developed renal failure and glomerulonephritis exhibited hematuria (11.1-32.1%) less frequent than proteinuria (62.3-83.3%). Even those with renal tumors or stones showed infrequent (14.3-27.9%) hematuria. Thus, urine protein and occult blood have different implications in mass screening.

Adult↗

[Lifestyles and renal damage--association of smoking, drinking and physical activity with subsequent proteinuria].

To examine the role of lifestyles in the subsequent development of renal damage, the association of smoking, drinking and physical activity with subsequent proteinuria was investigated utilizing a longitudinal study. The subjects were 7,701 males aged 20-84 years, who participated in health examinations at Aichi Prefectural Center of Health Care, Nagoya, Japan, both in 1989-1990 and 1992-1993, and who showed no proteinuria at the first examination. Lifestyles at the first examination were compared between 140 men with, and 7,561 men without, newly developed proteinuria at the second examination. Age-adjusted odds ratios (ORs) of lifestyle factors for proteinuria were computed, and further the ORs were adjusted for age, systolic blood pressure, fasting plasma glucose level and other covariates obtained using multiple logistic regression analysis. Major significant findings which emerged from the present study were as follows. (a) The greater the consumption of alcohol per day, the higher the risk of subsequent proteinuria (trend p = 0.003). Heavy drinkers who consumed more than 58 g of alcohol per day experienced an increased risk (OR relative to non-drinker: 2.52). (b) Those who exercised less than once a week, and those who avoided walking even a short distance were at an increased risk (OR: 1.46, 1.55, respectively). Heavy drinking and low physical activity were found to be significantly associated with an increased risk of subsequent proteinuria even after adjusting for the covariates. An increasing risk of subsequent proteinuria with number of cigarette smoked per day was observed by univariate and multivariate analysis but without statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Social activities in the elderly].

In order to clarify the status of social activities in the elderly, and to investigate an association between social activities and age, ADL, and geographical area, a self-administered questionnaire survey was conducted on the aged population in four areas in Japan. Social activities was defined as "activities which required contact with society" and was measured by 4 major facets of social activity, which were based on 21 questions on job activity, socially-related activities, learning activities, and personal activities. A total index was also developed by summarizing the 4 major facets as an indicator of whether the elderly is socially active or not as a whole. The following major findings emerged from this survey: (1) Rank correlation coefficients between each item which comprised 4 major activities were relatively high; (2) Excluding two activities, "shopping" and "attending senior school", aged men were more actively involved than women; (3) Trend in degrees of social activities differed by age among the 4 major facets, i.e., (a) job activity decreased with age, (b) socially-related activities and learning activities increased up to about 75 years old, and decreased thereafter, (c) personal activities were unaltered up to about 80 years old, and then decreased, and; (4) The elderly with low ADL had the lowest representation among the "highly active" in 4 major facets and total index as well.

Activities of Daily Living↗

[Validity of photographical dietary assessment; a preliminary analysis].

We estimated nutritional intake from color photographs taken of meals with a 35-mm camera, and compared them with the values calculated from the menu. Among 21 meals examined, the coefficient of correlation between the values by the photo method and those from examining the menu was appreciably high; 0.842 in energy, 0.828-0.931 in three major nutrients, and 0.745-0.940 in vitamins and minerals. The differences between the photo method and menu observation were 0-14.8% on average, and the coefficient of variation of the differences was 9.1-32.3%. Estimation of salt was, however, very poor, and the agreement was lower due to the cooking method used. Some differences were found among the dietitians in estimated values of several nutrients. The running cost was approximately 87-yen per meal, which may pose a problem for large-scale dietary surveys. Compared with the use of record, recall, and frequency questionnaire methods, the photo method was easily used by participants, especially those not used to cooking, and could be applied to eating out or for take-out food. Moreover, this method may provide not only quantitative data but also qualitative including eating atmosphere. When estimation is difficult due to the ingredients or recipe, combined use with record or recall methods can facilitate estimation. This photo method is thus considered to be a valid and feasible means of dietary assessment.

Food Analysis↗

Usefulness of narrow pedicled intercostal cutaneous perforator flap for coverage of the burned hand.

A narrow pedicled intercostal cutaneous perforator (np-ICP) flap is used for reconstruction of hand scar contractures after burns. This flap is designed with a narrow pedicle which includes some intercostal cutaneous perforators of 4-7th intercostal spaces, and with a wide distal area which lies over the costal cage and upper abdomen. Additionally the flap is thinned until only the subdermal vascular network is preserved in most of the wide distal area. It seems that this flap is more useful, not only functionally but also aesthetically, than conventional methods. This report describes the technique and concept, with a demonstration of some clinical examples.

Adult↗

Effect of amphipathic peptides with different alpha-helical contents on liposome-fusion.

The peptide-induced fusion of neutral and acidic liposomes was studied in relation to the amphiphilicities evaluated by alpha-helical contents of peptides by means of a carboxyfluorescein leakage assay, light scattering, a membrane intermixing assay and electron microscopy. An amphipathic mother peptide, Ac-(Leu-Ala-Arg-Leu)3-NHCH3 (4(3], and its derivatives, [Pro6]4(3) (1), [Pro2,6]4(3) (2), and [Pro2,6,10]4(3) (3), which have very similar hydrophobic moments, caused a leakage of contents from small unilamellar vesicles composed of egg yolk phosphatidylcholine and egg yolk phosphatidic acid (3:1). The abilities of the peptides to induce the fusion of the acidic liposomes increased with increasing alpha-helical content: in acidic liposomes the helical contents were in the order of 4(3) greater than 1 greater than 2 greater than 3 (Lee et al. (1989) Chem. Lett., 599-602). Electron microscopic data showed that 1 caused a transformation of the small unilamellar vesicles (20-50 nm in diameter) to large ones (100-300 nm). Based on the fact that these peptides have very similar hydrophobic moments despite of decreasing in the mean residue hydrophobicities to some extent, it was concluded that the abilities of the peptides to induce the fusion of liposomes depend on the extent of amphiphilic conformation evaluated by alpha-helical contents of the peptides in the presence of liposomes. For neutral liposomes of egg yolk phosphatidylcholine, all the proline-containing peptides showed no fusogenic ability but weak leakage abilities, suggesting that the charge interaction between the basic peptides and acidic phospholipid is an important factor to induce the perturbation and fusion of the bilayer.

Amino Acid Sequence↗

Role of corpus luteum function in embryo implantation.

The present study was undertaken to evaluate the role of corpus luteum function in the implantation process of cryopreserved embryos. Six patients with tubal infertility were studied, with a total of 27 fresh embryos being replaced following controlled ovarian hyperstimulation and in vitro fertilization. These embryo transfers failed to produce pregnancy. From the patients, 22 supernumerary embryos were cryopreserved and 10 viable frozen-thawed embryos were transferred in a subsequent natural cycle, resulting in 2 pregnancies. In 1 of the pregnancies, the serum concentrations of estradiol (E2) and progesterone (P4) in the midluteal phase were 29 pg/ml and 5.6 ng/ml, respectively. These values were considered to be below the physiological range. These data suggest that a pregnancy can be achieved in spite of low circulating E2 and P4 levels during the luteal phase, which are generally indicative of the luteal phase defect.

Adult↗

[A case of adenosquamous carcinoma with unknown origin and with superior vena cava syndrome as the first symptom].

This report is concerning a case of adenosquamous carcinoma having unknown origin and showing SVC syndrome as the first symptom. A 44 year-old man was admitted to our hospital because of facial edema at the beginning of April 1990. He was diagnosed as having a mediastinal tumor of the SVC syndrome type. Resection of the SVC tumor and part of the pericardium was performed on June 20, 1990. The operation had extraordinary findings. Lymph nodes adhering to tumor invaded the adjacent right side of the trachea and were situated in a rosette-like form. Furthermore, a part of the tumor stemmed into the lumen of the superior vena cava causing complete obstruction. The pathological diagnosis of the SVC tumor was adenosquamous carcinoma, however, no clinical examinations could identify its original matrix. Mediastinal tumors of unknown origin are reported as about 1% of all mediastinal tumors, and are responsible for 0.68% of all carcinomas in the mediastinum. This was one experience of a rare case of mediastinal tumor having unknown origin and showing SVC syndrome as the first symptom.

Adenocarcinoma↗

Ventilation-perfusion scintigram in diabetics.

We carried out ventilation and perfusion scintigraphies and pulmonary function tests in 20 diabetics under 50 years of age. 99mTc-MAA perfusion scintigrams showed evidence of minimal nonuniformity (MNU) in four cases (20%) and nonsegmental defect (NSD) in eight cases (40%). There was a ventilation defect in the single-breath image in one case (5%) and a delayed washout in three cases (15%) upon 133Xe ventilation scintigram. In the NSD group, the mean diffusing capacity value was abnormally low and the mean duration of the diabetes was long compared with other groups. The frequency of perfusion defects was higher than that of ventilation abnormalities; moreover, abnormal findings on ventilation scintigrams were very mild compared with those of perfusion defects. Perfusion defects correlated significantly with a decrease in diffusing capacity. These findings suggest that the disturbance in pulmonary arterial perfusion caused a decrease in diffusing capacity in diabetics.

Adult↗

In vivo and in vitro studies in a patient with cyclical Cushing's disease showing some responsiveness to bromocriptine.

In vivo and in vitro studies were carried out in a 37-year old female with cyclical Cushing's disease. Preoperative studies revealed periodic secretions of urinary corticosteroids occurring with a cyclicity of 2-3 weeks. On transsphenoidal surgery, a microadenoma was visualized in the anteroinferior portion of the anterior pituitary. Gel filtration analyses of the adenoma and surrounding tissues revealed increased concentrations of beta-endorphin and an activated conversion of beta-lipotropin to beta-endorphin in the adenoma compared with the surrounding tissues. These findings were in agreement with the characteristics previously reported for corticotroph adenomas. However, unexpectedly, concentrations of ACTH and beta-lipotropin in the adenoma were only slightly higher than those in the surrounding tissues. Precise mechanisms underlying this unusual finding were elusive, but it may have been due to the periodic nature of her hypercortisolism. In addition, this patient was reproducibly responsive to bromocriptine (2.5 mg, per os) with a reduction of the plasma cortisol level. Although this may suggest an intermediate lobe subtype of Cushing's disease as proposed by Lamberts' group, our case did not have any other characteristic suggestive of this proposed variant. However, it is tempting to speculate that cyclical changes in the central dopaminergic tone may have been at least a partial trigger for the periodic hormonogenesis in this patient.

Adrenocorticotropic Hormone↗

[Evaluation of prognosis in patients with old myocardial infarction--using 201Tl myocardial scintigraphy and 99mTc cardiac scintigraphy].

To evaluate the prognosis in 57 patients with old myocardial infarctions, 201Tl myocardial scintigraphy and 99mTc-HSA gated blood pool scan had been done as a 5-year follow up study. We subdivided into two groups; group I (over 60 years) and group II (under 60 years). Cardiac index (CI) and right ventricular ejection fraction (RVEF) did not change significantly, however left ventricular ejection fraction (LVEF) changed significantly (p less than 0.05). Correlationship between CAG score and delta LVEF by handgrip exercise test was y = -1.34 x +3.61 (n = 44, r = -0.400, p less than 0.01). Otherwise, Tl defect ratio between first and final examination did not show the significant change in two groups. In conclusion, nuclear examination (cardiac function and myocardial blood flow) is significant to evaluate the prognosis in patients with myocardial infarction.

Aged↗

[Oocyte fertilizability and hormonal environment of human preovulatory follicles in hyperstimulated cycles in an in vitro fertilization program: Are mature preovulatory follicles undergoing atresia?].

Steroid hormones in preovulatory follicular fluid, maturity of the oocyte-corona-cumulus complex (OCCC), and oocyte fertilizability were studied in 55 hyperstimulated cycles in 40 patients who were indicated for in vitro fertilization and embryo transfer due to tubal infertility. Aspirated follicles were categorized into four groups according to the degree of oocyte maturation and fertilizability, i.e. follicle (Fol)-1 (non-fertilized, intermediate maturation), Fol-2 (fertilized, intermediate maturation), Fol-3 (fertilized, full maturation), and Fol-4 (non-fertilized, full maturation). Estradiol (E2), progesterone (P), and delta 4- androstenedione (delta 4A) concentrations were highest in Fol-3, being lower in Fol-2 and Fol-1 sequentially. Fol-3 contained significantly more E2 and P than did Fol-1, showing that the degree of oocyte maturation and fertilizability correlate with concentrations of E2 and P in the follicles. A comparison of Fol-3 and Fol-4 revealed significantly higher concentrations of delta 4A in Fol-4, whereas differences in E2 and P concentrations were not significant although Fol-4 values were lower. This comparison indicated that Fol-4 were already undergoing atresia at the time of oocyte retrieval, containing morphologically mature OCCC which had lost fertilizability. This study shows that steroid hormones in the follicular fluid reflect oocyte viability and fertilizability, and suggests that preovulatory follicles with mature oocytes can also undergo atresia.

Chorionic Gonadotropin↗