Twin concordance for DSM-III-R schizophrenia.

The monozygotic (MZ)/dizygotic (DZ) concordance rates for schizophrenia and the relationship between schizophrenia and schizophrenic spectrum disorders were studied in a sample of 31 MZ and 28 DZ schizophrenic probands and their co-twins. All subjects were personally interviewed with structured diagnostic instruments and classified according to DSM-III-R criteria. The concordance rates of 48% for MZ twins and 4% for DZ twins indicate a genetic transmission of DSM-III-R schizophrenia. In addition to the schizophrenic co-twins, 3 MZ co-twins had a noneffective psychotic disorder, thus supporting the hypothesis that genes are involved in the development of Axis I schizophrenic spectrum disorders. Schizotypal and paranoid personality disorders were observed in both MZ and DZ co-twins. These disorders may be familially related to schizophrenia, but a genetic relationship was not confirmed for the Axis II spectrum disorders. A substantial number of MZ co-twins of schizophrenic probands had no mental disorder.     

Expression of enhancer of zeste homologue 2 is significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer.

The polycomb group protein enhancer of zeste homologue 2 (EZH2) has been linked to invasive properties of aggressive breast cancer. In this report, tissue microarray analysis of 190 breast carcinomas from a nested case-control study shows that EZH2 is significantly associated with interval breast cancers. Further, a strong relationship was found with tumor cell proliferation (by Ki-67 expression), locally advanced disease, metastasis at presentation, markers of the basal epithelial phenotype (positivity for cytokeratin 5/6 or P-cadherin), and p53 status. EZH2 expression was also significantly associated with glomeruloid microvascular proliferation, an aggressive angiogenic phenotype. For prediction of aggressive disease (any event of locally advanced disease, lymph node spread, or distant spread), EZH2 was the only variable of significance in multivariate analysis, whereas no additional information was given by Ki-67. Although EZH2 expression was significant in univariate survival analysis, only tumor cell proliferation and lymph node status were significant in the final multivariate model. In conclusion, our findings indicate an important relationship not only between EZH2 and markers of tumor cell proliferation but also with aggressive disease. These findings might be practically important and relevant because the polycomb group proteins have recently been suggested as candidates for targeted therapy.     

Creutzfeldt-Jakob disease. Infection of infancy or childhood?

A 51-year-old man who died of Creutzfeldt-Jakob disease (CJD), had transient dyskinesias with intention myoclonus and exaggerated startle reaction in early life. This may suggest a link between myoclonic encephalopathy of infants and CJD, and an incubation period of more than 40 years of the transmissible agent of CJD.     

Newer Concepts of Dietary Therapy in IDDM in Children

The most important aspects of the diet for diabetic children are: 1. The timing of the meals. For the main meals, the time of the school meal and of the family dinner should be followed. Smaller meals will be necessary in between, with a total of about 6 meals daily. 2. The size of the meals and total amount of energy must be adjusted to the need of the children, and to the insulin type, dose and time of injection. A reasonable variation in energy intake is supported. Extra intake related to exercise will not only be taken on the days of exercise but also on the day after. This is supported by our own investigation. The appetite of the children should also be used in this regulation. Newer studies are summarized about the change in absorbability of starch by heating and cooking, and the effect on blood glucose of potatoes, rice and bread, different fruits and sorbitol. A long-term study of different fibres in bread is presented. A decrease both in mean bloodglucose and HbAl was found to be induced both by bran and by guar. The practical accomplishment of the diet is a larger problem than the theoretical ones.     

Extensive variation and low heritability of DNA methylation identified in a twin study

Disturbance of DNA methylation leading to aberrant gene expression has been implicated in the etiology of many diseases. Whereas variation at the genetic level has been studied extensively, less is known about the extent and function of epigenetic variation. To explore variation and heritability of DNA methylation, we performed bisulfite sequencing of 1760 CpG sites in 186 regions in the human major histocompatibility complex (MHC) in CD4+ lymphocytes from 49 monozygotic (MZ) and 40 dizygotic (DZ) twin pairs. Individuals show extensive variation in DNA methylation both between and within regions. In addition, many regions also have a complex pattern of variation. Globally, there appears to be a bimodal distribution of DNA methylation in the regions, but a significant fraction of the CpG sites are also heterogeneously methylated. Classification of regions into CpG islands (intragenic and intergenic), 5' end of genes not associated with a defined CpG island, conserved noncoding regions, and random CpG sites shows region-type differences in variation and heritability. Analyses revealed slightly lower intra-pair differences among MZ than among DZ pairs, suggesting some genetic influences on DNA methylation variation, with most of the variance attributed to nongenetic factors. Overall, heritability estimates of DNA methylation were low. Our heritability estimates are, however, somewhat deflated due to the presence of batch effects that artificially inflate the estimates of shared environment.