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Biomedical subjects

R Aoki

Publications and source records attributed to R Aoki.

At least 37 records · Page 2Linked to original sources

Trends in site-specific mortality from oral and pharyngeal cancer among Japanese males, 1950-94.

In order to obtain some etiological clues for oral and pharyngeal cancer in Japanese males, we examined mortality trends from cancer of the lip, buccal cavity and pharynx by site with other descriptive epidemiological features (1950-94). The data were obtained from Vital Statistics (Ministry of Health and Welfare, Japan). The 45-year trend in mortality was evaluated by computing crude and age-adjusted mortality rates, age-specific mortality rates, with birth cohort analysis. The crude mortality rate from cancer of the lip, buccal cavity and pharynx has increased by 3.7-fold, and age adjusted mortality rate by 1.7-fold in the 45-year period, with different mortality trends by site. In general, age-specific mortality has also been increasing with advancing age. The birth cohort analysis showed that the higher the mortality rate, the younger the birth cohort, but with different effects of birth cohort by site. Mortality from cancer of the lip, buccal cavity and pharynx has consistently been increasing in Japanese males from 1950 to 1994, with similar upward mortality trends for some specific sites.

Adult↗

Expression and characterisation of the heavy chain of tetanus toxin: reconstitution of the fully-recombinant dichain protein in active form.

Tetanus toxin, composed of a disulphide-linked heavy (HC) and light (LC) chain, preferentially blocks the release of inhibitory neurotransmitters in the spinal cord by Zn2+-dependent proteolytic cleavage of synaptobrevin. This intoxication involves binding via HC to ecto-acceptors on peripheral nerve endings, followed by internalisation and retrograde transportation to its prime site of action in central neurons. To facilitate exploitation of the toxin's unique activities, HC was expressed at a high level in Escherichia coli as a fusion with maltose binding protein; after cleavage by thrombin, free HC was isolated and its identity confirmed by Western blotting and N-terminal microsequencing. The expressed and native HC gave very similar circular dichroism spectra, excluding any gross differences in their folded structures. Recombinant HC antagonised the neuromuscular paralysing activity of the native toxin, by competing for binding to neuronal ecto-acceptors. The HC was reconstituted with bacterially-expressed LC to create disulphide-bridged dichain toxin that blocked neuromuscular transmission. The fully-recombinant toxin produced spastic paralysis in mice characteristic of the blockade of central inhibitory synapses, revealing that it undergoes axonal transport to the spinal cord, like the native toxin but with a reduced efficacy. This first report of the large-scale production of recombinant tetanus toxin in active form should facilitate studies on the use of engineered innocuous forms of the toxin as neuronal transport vehicles.

Amino Acid Sequence↗

A simple food frequency questionnaire for Japanese diet--Part I. Development of the questionnaire, and reproducibility and validity for food groups.

We developed a simple food frequency questionnaire (FFQ) based on one-day dietary records (DRs) among 1001 subjects in Nagoya, Japan. A total of 97 foods and dishes were selected through a two-step procedure; first by ranking food items according to the contribution to the population intake of nutrient variables, and second by stepwise multiple regression analyses of individual food items as the independent variables and of total nutrient intake as the dependent variables. For simplicity, questions on portion sizes were not included except for a few selected food items, which resulted in short time (about 20 minutes) to complete the questionnaire. This FFQ was validated for food groups by referring to four 4-day DRs among 88 men and women in central Japan, from 1996 to 1997. The energy-, sex- and age-adjusted test-retest correlation coefficients between the two FFQs administered at an one year interval ranged from 0.34 to 0.78. The de-attenuated, energy-, sex- and age-adjusted correlation coefficients between the second FFQ and the DRs were larger than 0.40 for most food groups, indicating the usefulness of this simple FFQ with its sufficient validity in epidemiological surveys.

Adult↗

A simple food frequency questionnaire for Japanese diet--Part II. Reproducibility and validity for nutrient intakes.

A self-administered 97-item simple food frequency questionnaire (FFQ), without portion size questions for most items, was completed twice at an one-year interval by 88 men and women in central Japan to evaluate its reproducibility. This FFQ was further validated by referring to four 4-day weighed dietary records (DRs) which were performed at 3-month intervals. Mean energy and 18 nutrient intakes measured by the first and the second FFQs were quite similar to those measured by the DRs. In our reproducibility study, Pearson and intraclass correlation coefficients, adjusted for energy intake, sex and age, ranged from 0.48 to 0.82 (median = 0.67). In the validation study, adjusted and de-attenuated correlation coefficients between the second FFQ and the DRs ranged from 0.42 for iron to 0.83 for calcium (median = 0.61). The proportion of subjects classified by the FFQ into the same or adjacent quintiles defined by the DRs was between 65.9% and 83.0% (median = 69.9%). These findings essentially suggested that our FFQ is well reproducible and sufficiently valid, and therefore, reasonably useful for nutritional epidemiological studies for Japanese diets, particularly for those of Tokai Area.

Adult↗

[Sudden death of clinically unknown origin. An overview of postmortem examinations in Japan].

To elucidate the possible causes of sudden unexpected deaths (SUD) in Japan, we over-viewed autopsy findings described in the Annual of the Pathological Autopsy Cases in Japan, Vol. 35-37, 1992-1994. A total of 313 cases of SUD of clinically unknown origin (age > = 5 year) were found among the 95,142 autopsy cases listed in the above compilation. The direct causes of death, if identified, were described with their incidences. When the direct cause was undetermined, the most dominant pathological finding was listed. The difference in age between identified and unidentified groups was also studied. In 225 (72%) out of 313 SUD, direct causes of death were clarified as follows: cardiovascular diseases in 140 (acute myocardial infarction in 75), pulmonary diseases in 32, cerebrovascular diseases in 17, and gastrointestinal or hepatic disease in 17 cases. Even among 88 cases whose direct causes of death were unclear, 55 had cardiovascular abnormalities including myocardial hypertrophy and ischemic changes. No life-threatening abnormalities were found in 23 SUD cases, most of whom were men in their forties or younger. This study indicates that autopsy is helpful to reveal the cause of SUD. It also suggests cardiovascular diseases are the leading causes of SUD of clinically unknown origin.

Autopsy↗

Evaluating motor end-plate-targeted injections of botulinum toxin type A in a canine model.

Tarsal joint forces were measured in dogs over 70 days following botulinum toxin type A (BTX-A) injections. Three dogs were injected at motor end-plates located by electromyography (EMG), while 3 dogs were similarly injected, but without EMG guidance. Extension forces were significantly (P < 0.05) smaller in limbs injected at motor end-plates than in corresponding limbs on days 14 and 35. There were no significant differences at other times. Using these techniques, EMG end-plate targeting potentiates effects of BTX-A.

Animals↗

MUC-1 expression as a predictor of the curative endoscopic treatment of submucosally invasive colorectal carcinoma.

PURPOSE: This study was undertaken to clarify the clinical significance of MUC-1 expression in the endoscopic treatment of colorectal carcinoma with submucosal invasion. METHODS: One hundred eighty-four colorectal carcinomas with submucosal invasion were examined. The depth of submucosal invasion was classified as scanty or massive. The histologic subclassification at the deepest invasive portion was defined as well-differentiated, moderately well-differentiated, moderately to poorly differentiated, poorly differentiated, or mucinous adenocarcinoma. MUC-1 expression was examined immunohistochemically at the deepest invasive portion. In addition, the Ki67 labeling index was also examined immunohistochemically. RESULTS: Lymph node metastases were detected in 28 (15.2 percent) of 184 lesions. Lesions with both scanty submucosal invasion and well-differentiated or moderately well-differentiated adenocarcinomas had no lymph node metastases. MUC-1 expression was detected in 88 (47.8 percent) of 184 lesions and correlated significantly with the presence of lymph node metastases. The Ki67 labeling index also correlated significantly with lymph node metastases. Furthermore, lesions with both MUC-1-negative and low Ki67 labeling index showed no lymph node metastases, even in lesions with massive submucosal invasion. Multivariate analysis indicated that MUC-1 expression was one of the most important risk factors for lymph node metastases and histologic grade among the clinicopathologic factors usually examined. CONCLUSION: MUC-1 expression is one of the accurate predictors of the presence of lymph node metastases among the clinicopathologic factors commonly used. Combined analysis of MUC-1 expression and Ki67 labeling index may be a useful indicator of lymph node metastases and may broaden the indications for the curative endoscopic treatment of carcinoma with massive submucosal invasion.

Adenocarcinoma↗

Primary cutaneous Langerhans cell histiocytosis in an adult.

A 76-year-old man with Langerhans cell histiocytosis was admitted with an asymptomatic, dark red nodule on his left buttock. Histologic examination of the nodule showed a dense dermal infiltrate of histiocytic cells with bean-shaped nuclei; these cells reacted with antibodies to S-100 and CD1a. Ultrastructural analysis showed Birbeck granules in the cytoplasm of the histiocytic cells. Inguinal lymph node involvement subsequently developed in the patient and cutaneous nodules recurred three times in the inguinal area. Four years have passed since he first was admitted to our hospital with the cutaneous nodule on his buttock, and he is doing well without any intensive treatment except wide excision of the nodules and inguinal lymph nodes. We believe this case should be classified as one of "benign" primary cutaneous Langerhans cell histiocytosis based on the clinical course.

Aged↗

Effect of gelonin immunoconjugate with monoclonal antibody MSN-1 to endometrial adenocarcinoma on antigen-producing tumor cells in vivo.

Missile therapy, which destroys cancer cells specifically, has been advocated as an effective modality for the treatment of carcinoma. We have developed an immunoconjugate consisting of the monoclonal antibody MSN-1 (IgM), which reacts strongly with endometrial adenocarcinomas, combined with a plant hemitoxin named gelonin via a disulfide bond using N-succinimidyl-3-(2-pyridyldithio) propionate and 2-iminothiolane, and examined its selective cytotoxicity in athymic mice. The reductions in resected weights of target tumor cells, at the local site of MSN-1-gelonin immunoconjugate treatment, were 96% with local administration and 75% with caudal vein administration, as compared with the untreated group. There was no weight loss in treated mice. Our results suggest that this MSN-1-gelonin immunoconjugate has potential clinical applications in the treatment of endometrial adenocarcinomas.

Adenocarcinoma↗

Estimated number of patients with chronic renal failure but not with end-stage renal disease in Japan: comparisons between two estimation methods.

We estimated the number of patients with chronic renal failure (CRF) but not with end-stage renal disease (ESRD) in Japan by two methods: a nationwide survey and an estimation using incidence rates of ESRD among CRF patients as well as the number of incident ESRD. The former estimated the number of patients with CRF but not with ESRD as 154,000 (95% confidence interval 139,000-168,000), while so did the latter as 142,000 (133,000-150,000). It follows that the number of CRF patients including ESRD could amount to more than 300,000, which would give a substantial impact on public health in Japan. Despite some own methodological issues in estimation, the two estimates were reasonably in good agreement: supporting their methodological validity in estimation, since sources of errors appeared to be quite independent of each other.

Adult↗

Descriptive epidemiology of pancreatic cancer in Japan.

This paper aimed to explore descriptive epidemiological features of pancreatic cancer in Japan, by examining secular trends in mortality (1950-1995) and incidence rates (1975-1991), and also to discuss background factors possibly ascribable to the recent variation in mortality and incidence rates. The age-adjusted mortality rate (adjusted by the 1985 model population) has increased by approximately 9-fold in both males (from 1.4 to 12.5 per 100,000 population) and females (from 0.8 to 6.8 per 100,000 population) between 1950 and 1995. But it began to level off in both sexes since 1985. The age-adjusted incidence rate has remained plateau in both sexes, but likely showed a downward trend since 1988 in females. The older age groups showed the most steep increasing gradient in both age-specific mortality and incidence rates in both sexes, whereas a little or no apparent increase was observed in young age groups. Diagnostic improvement and increased cigarette consumption were believed to be the two major factors contributing to the increased mortality and incidence rates in Japan, but further epidemiological studies will be required to clarify possible background factors for the recent levelling-off of the mortality and incidence rates.

Adult↗

[Assessment method for supporting programs for social activities of the elderly by city, town and village governments in Japan].

OBJECTIVES: The authors developed a questionnaire to assess the activities of supporting programs for social activities for the elderly conducted by city, town and village governments, based on the number of such programs. This study aims to examine the validity of the questionnaire. METHODS: We conducted a study of 145 cities, towns and villages from two prefectures in Japan using the questionnaire. The questionnaire asks government officers whether they had each of 32 programs, and the number of programs in total, as well as each of four domains of social activities (i.e., employment, social participation/volunteering, education/training, individual activities) were calculated. They were also asked to classify each of the programs into one of four domains of social activity to which the programs were most related; they were asked to rate how active the programs were for each domain in their community. To examine the validity of the questionnaire, the following indicators were assessed: (1) proportion of reported programs which were not covered by the questionnaire; (2) concordance of classification of programs into four domains of social activity with those judged by government officers; (3) correlations between number of programs and self-rated activity levels by government officers; and (4) correlations of number programs with characteristics of cities, towns or villages. RESULTS: The results indicated that the list of programs covered most of the programs. Proposed classification of programs into four domains of social activities which they are most related to agreed with judgments by officials. The number of programs positively correlated with self-rated activity levels by officers for employment and education/training domains in both prefectures; and for social participation/volunteering and individual activities in one of the prefecture. The numbers of programs for employment of the elderly positively correlated with the total population of the community, number of staffs, proportion of people employed in the tertiary industries and total budget for social welfare of the elderly; it negatively correlated with proportion of people employed in the primary industries. CONCLUSION: It is suggested that the list of programs in the questionnaire is applicable and assessment based on the number of programs by four social activity domains is valid to some extent in either prefecture. The questionnaire can be improved further, e.g., by adding other programs to the list.

Aged↗

Newly developed diabetic retinopathy and its preceding changes in biological markers.

To disclose the chronological changes prior to the manifestation of diabetic retinopathy (DR), we analyzed the time course of biological markers among apparently healthy diabetic subjects in a case-control study of 21,579 adults who had undergone comprehensive health examinations for > or = 10 years. We identified 54 cases who had newly developed DR, and selected 108 adults without fundus abnormalities, matching them for sex, age, and fasting plasma glucose (FPG) at the onset of the patient group's retinopathy as a referent group from the same population. In a multivariate analysis, a high average FPG (> 175 mg/dl) and a final-year FPG reduction (< -3%) were significantly associated with a 5.4 (95% CI, 1.8-15.7)- and 5.0 (95% CI, 1.0-24.7)-fold increased risk of DR, respectively. Thus, we surmised that sustained hyperglycemia and a subsequent drop in FPG might promote retinopathy in non-insulin dependent diabetes mellitus.

Biomarkers↗

Epidemiological features of moyamoya disease in Japan: findings from a nationwide survey.

To estimate an annual number of patients treated for Moyamoya disease in Japan and to describe the clinico-epidemiological features, a nationwide epidemiological survey was conducted in 1995. The study consisted of two questionnaires, which were distributed to departments randomly selected, of neurosurgery, neurology and pediatrics in hospitals throughout Japan. The first questionnaire inquired the number of the patients treated in 1994 and the second one detailed clinico-epidemiological information of each patient reported. Following major epidemiological findings emerged from the study: (a) The total annual number of patients treated for Moyamoya disease was estimated as 3900 (95% confidence interval (CI) 3500-4400) in Japan 1994, with the prevalence and incidence rates of 3.16 and 0.35 per 100,000 population, respectively; (b) the sex ratio (females to males) of the patients was 1.8; (c) the peak of age distribution of the patients was observed in 10-14 years old and a smaller peak in their forties; (d) the age at onset was under 10 years old in 47.8% of the patients, but some had developed the disease at the age of 25-49 years; (e) family history of Moyamoya disease was found in 10.0% of the patients; and (f) about 75% of the patients had normal activity of daily life or working ability even before treatment. The present findings were quite comparable with those obtained in the previous nationwide epidemiological survey in 1990.

Adolescent↗

Estimated prevalence and incidence of adult Still's disease: findings by a nationwide epidemiological survey in Japan.

To estimate prevalence and incidence of adult Still's disease in Japan, and to describe the epidemiological features of the patients, a nationwide epidemiological survey was conducted in 1994. The study consisted of two questionnaires which were distributed to the heads of the relevant departments, randomly sampled, in hospitals throughout Japan. Following major epidemiological findings emerged from the study: (a) The total annual number of patients treated for adult Still's disease was estimated as 1,100 in 1993 in Japan. The estimated crude prevalence among those aged 16 years or older were calculated as 0.73 and 1.47 per 100,000 population for males and females, respectively, with the corresponding crude incidence rate of 0.22 and 0.34. (b) The sex ratio (female to male) of the reported patients was 2.1. This female predominance might be specific to Japan, though additional surveys in other countries will be warranted. The mean age of the patients was 38.1 years, and female patients tended to be older than male ones; 50% of the female patients aged 40 years or older, while so did only 28% of the male patients.

Adolescent↗

Smoking habits, local brand cigarettes and lung cancer risk in Okinawa, Japan.

To disclose the association between smoking habits and lung cancer in Okinawa, Japan, we analyzed the data from a case-control study conducted from 1988 to 1991. The analysis, based on 333 cases and 666 age-, sex- and residence-matched population controls, provided the following major findings. (a) The odds ratios (ORs) for current smokers relative to nonsmokers were much greater for squamous cell carcinoma than for adenocarcinoma. The OR was 9.82 for squamous cell carcinoma and 2.18 for adenocarcinoma in males, 28.2 and 1.14, correspondingly, in females. (b) Males who quit smoking for 20 years or more demonstrated no elevated lung cancer risk. (c) Among male current smokers, the more the number of cigarettes smoked per day, the higher the lung cancer risk for both cell types, but particularly for squamous cell carcinoma. In contrast, deep smoke inhalation significantly increased the risk for adenocarcinoma in particular. (d) Okinawan brand cigarettes were more strongly associated with the risk, compared with other brand ones. This finding might partly explain the higher frequency of lung cancer in males with the relatively lower smoking rate in Okinawa.

Adenocarcinoma↗

[Development of index of social activities for the elderly].

In order to develop indices of social activities for the elderly, two surveys with 2 year intervals were conducted on the same 5,201 elderly subjects in four areas in Japan using a self-administered questionnaire. Social activities were defined as "activities which required contact with society" and were measured by 4 major facets of social activities, which were based on 21 questions relating to job activity, socially-plated activities, learning activities, and personal activities. The results were as follows; 1. The Wilcoxon scores in indices for 4 facets were given in sex and age groups. 2. Means of scores of indices increased with the degree of social activities from a subjective judgment. 3. Rank correlation coefficients between indices in two surveys were 0.60-0.71 for the persons whose answers were "no" to the question "did degrees of your activities change over the two years?" 4. Differences between indices in two surveys were higher in the persons with answers of "increase" to the above question than those with answers of "no", and were lower in those with answers of "decrease". These findings suggest that indices are available for assessing social activities as indicated by the reproducibility, validity and responsiveness found in this study.

Activities of Daily Living↗

Newly developed ST-T abnormalities on the electrocardiogram and chronologic changes in cardiovascular risk factors.

An ST-T abnormality on an electrocardiogram (ECG) is known to independently predict subsequent morbidity and mortality from cardiovascular diseases. But how ST-T abnormality develops in relation to chronologic changes in cardiovascular risk factors has not been fully discussed. Sixty-eight men whose ECG had been initially normal but who exhibited ST-T abnormality later (ST-T subjects) were identified among 21,579 apparently healthy adults who had undergone comprehensive health examinations for > 10 years. Echocardiography proved that 26 of 29 examinees among ST-T subjects had left ventricular hypertrophy. Antihypertensive drugs were given to 26 of the ST-T subjects. Their cardiovascular risk factors were chronologically reviewed from 10 years before the onset of definite ST-T abnormality, and were compared with those of 68 men whose ECG had remained consistently normal for 10 years (controls). Mean values of systolic and diastolic blood pressure gradually increased over 10 years (from 127/78 to 144/84 mm Hg) among ST-T subjects, but showed little change (from 122/76 to 124/77 mm Hg) during the same period in controls. The time course of blood pressure over 10 years was similar in ST-T subjects, irrespective of final blood pressure level. Mean serum cholesterol and glucose increased over 10 years in both ST-T and control subjects. Uric acid decreased over 10 years (from 6.1 to 5.6 mg/dl) only in ST-T subjects. Multivariate analysis revealed that blood pressure and uric acid before onset of ST-T abnormality were chronologically changed independent of other risk factors. The time course of risk factors may be of great importance in the development of cardiovascular disorders.

Blood Pressure↗