Background:  A causal relationship between the measles, mumps, and rubella (MMR) vaccine and occurrence of autism spectrum disorders (ASD) has been claimed, based on an increase in ASD in the USA and the UK after introduction of the MMR vaccine. However, the possibility that this increase is coincidental has not been eliminated. The unique circumstances of a Japanese MMR vaccination program provide an opportunity for comparison of ASD incidence before and after termination of the program. Methods:  This study examined cumulative incidence of ASD up to age seven for children born from 1988 to 1996 in Kohoku Ward (population approximately 300,000), Yokohama, Japan. ASD cases included all cases of pervasive developmental disorders according to ICD‐10 guidelines. Results:  The MMR vaccination rate in the city of Yokohama declined significantly in the birth cohorts of years 1988 through 1992, and not a single vaccination was administered in 1993 or thereafter. In contrast, cumulative incidence of ASD up to age seven increased significantly in the birth cohorts of years 1988 through 1996 and most notably rose dramatically beginning with the birth cohort of 1993. Conclusions:  The significance of this finding is that MMR vaccination is most unlikely to be a main cause of ASD, that it cannot explain the rise over time in the incidence of ASD, and that withdrawal of MMR in countries where it is still being used cannot be expected to lead to a reduction in the incidence of ASD.

Abstract-The tension in isolated ring preparations of the thoracic aortae from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) was measured isometrically to study the differences in testosterone-induced relaxation between WKY and SHR aortic rings. Testosterone (9 to 300 mol/L) induced a concentration-dependent relaxation in both WKY and SHR aortic rings, and the relaxation induced by testosterone was greater in SHR than WKY. The relaxation induced by testosterone was significantly reduced by denudation of endothelium in SHR but not WKY. Indomethacin, an inhibitor of cyclooxygenase, and N G -nitro-L-arginine, an inhibitor of nitric oxide (NO) synthase, showed little influence on the relaxation induced by testosterone in both WKY and SHR aortic rings. Glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, significantly reduced the relaxation induced by testosterone in both WKY and SHR aortic rings, although the extent of reduction was greater in WKY than SHR. On the other hand, 4-aminopyridine, a selective inhibitor of voltage-dependent potassium channels, and tetraethylammonium, an inhibitor of calcium-activated potassium channels, significantly reduced the relaxation induced by testosterone in SHR but not WKY. These results suggest that the mechanisms of testosterone-induced vasorelaxation in both WKY and SHR involve, in part, ATP-sensitive potassium channels in the thoracic aortae and that in SHR aortic rings, testosterone may release endothelium-derived substances that may cause hyperpolarization of the cells by a mechanism that involves potassium channels. Moreover, the data show differences between WKY and SHR in the function of ATP-sensitive, voltage-dependent, and calcium-activated potassium channels. (Hypertension. 1999;34:1232-1236.) Key Words: testosterone Ⅲ endothelium Ⅲ rats, inbred SHR Ⅲ rats, inbred WKY Ⅲ aorta Ⅲ potassium channels H ypertension and coronary heart disease occur more frequently in men than in premenopausal women. 1 A decrease in LDLs and an increase in HDLs are considered to be one of the mechanisms by which estrogen reduces the risk factors of coronary heart disease. 2 Studies have reported that hypertensive men and premenopausal women have lower levels of plasma androgen but higher levels of plasma estrogen than controls. 3,4 Males become more hypertensive than females in genetic and nongenetic rat models of hypertension, and this sexual dimorphism is reduced by gonadectomy. 5,6 Also, reports have indicated that androgen may contribute to the development of hypertension in spontaneous hypertensive rats (SHR) through sustained enhancement of tyrosine hydroxylase activity, which leads to increased norepinephrine (NE) levels in blood vessels. 7,8 On the other hand, several reports consider the direct relaxing effects of estrogen on the vasculature in vitro, 9 -13 but few consider the direct relaxing effects of testosterone on the vasculature, 14,15 and only normotensive animals have been used in these studies. Whether these sex steroids affect phar...

Most studies on the frequency of autism have had methodological problems. Most notable of these have been differences in diagnostic criteria between studies, degree of cases overlooked by the initial screening, and type of measurement. This study aimed to replicate the first report on childhood autism to address cumulative incidence as well as prevalence, as defined in the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) Diagnostic Criteria for Research. Here, the same methodological accuracy (exactness of a measurement to the true value) as the first study was used, but population size was four times larger to achieve greater precision (reduction of random error). A community-oriented system of early detection and early intervention for developmental disorders was established in the northern part of Yokohama, Japan. The city's routine health checkup for 18-month-old children served as the initial mass screening, and all facilities that provided child care services aimed to detect all cases of childhood autism and refer them to the Yokohama Rehabilitation Center. Cumulative incidence up to age 5 years was calculated for childhood autism among a birth cohort from four successive years (1988 to 1991). Cumulative incidence of childhood autism was 27.2 per 10000. Cumulative incidences by sex were 38.4 per 10000 in males, and 15.5 per 10000 in females. The male:female ratio was 2.5:1. The proportions of children with high-functioning autism who had Binet IQs of 70 and over and those with Binet IQs of 85 and over were 25.3% and 13.7% respectively. Data on cumulative incidence of childhood autism derived from this study are the first to be drawn from an accurate, as well as precise, screening methodology.

Cumulative incidence and prevalence were 16.2 per 10,000 and 21.1 per 10,000, respectively. Children with high-functioning autism who had IQs of 70 and over constituted approximately half of all the children with childhood autism. CONCLUSION. It was confirmed through better detection of high-functioning cases that childhood autism in Japan is more common than formerly estimated.

NADP-dependent malic enzyme (NADP-ME) is a major decarboxylating enzyme in NADP-ME-type C4 species such as maize and Flaveria. In this study, chloroplastic NADP-ME was transferred to rice (Oryza sativa L.) using a chimeric gene composed of maize NADP-ME cDNA under the control of rice light-harvesting chlorophyll-a/b-binding protein (Cab) promoter. There was a 20- to 70-fold increase in the NADP-ME activity in leaves of transgenic rice compared to that in wild-type rice plants. Immunocytochemical studies by electron microscopy showed that maize NADP-ME was mostly localized in chloroplasts in transgenic rice plants, and that the chloroplasts were agranal without thylakoid stacking. Chlorophyll content and photosystem II activity were inversely correlated with the level of NADP-ME activity. These results suggest that aberrant chloroplasts in transgenic plants may be caused by excessive NADP-ME activity. Based on these results and the known fact that only bundle sheath cells of NADP-ME species, among all three C4 subgroups, have agranal chloroplasts, we postulate that a high level of chloroplastic NADP-ME activity could strongly affect the development of chloroplasts.