Epidemiological analysis of poliomyelitis cases in 1994, China

In 1994, the number of reported polio cases was 307 in China. This number was 53% lower than that in 1993, and was the lowest record ever in China. In 1994, the distribution of polio cases was highly dispersed and the number of outbreak was reduced obviously. Of 225 counties which reported polio cases in 1994, polio outbreak occured in 2 counties. Cases due to polio outbreak accounted for 4.2% of the total cases. The distribution of polio wild virus was narrow but the regional difference still existed. In the southeast, high risk region for polio consisting Guangdong, Hainan, Fujian three provinces, the number of polio cases decreased remarkably in 1994. On the contrary, in the southwest region which, consisting Guangxi, Yunnan, Guizhou, Sichuan four provinces, the number of polio cases increased obviously, accounted for approximately a half of the total number in 1994. During the coming 1 to 2 years, we should emphasis on these regions and provinces where high incidence was noticed in our polio eradication program. Those provinces should include Xinjiang, Fujian. Hubei three provinces that polio wild virus was identified in 1994, and Guangxi, Sichuan, Guizhou, Yunnan in the south west region as well. We should further increase Polio vaccination coverage of children especially floating and unplanned ones through strengthening routine immunization and carring out new national immunization day activity.     

Comparison of the kinetics of injectable testosterone in eugonadal and hypogonadal men

Serum reproductive hormone levels were measured serially after eugonadal and hypogonadal men had received either a 200-mg or a 100-mg intramuscular injection of testosterone enanthate. The calculated mean integrated testosterone and estradiol levels indicated that the 200-mg testosterone enanthate injection in the hypogonadal subjects maintained eugonadal levels of these hormones through day 11. The 100-mg dose maintained eugonadal levels of these hormones through day 11. The 100-mg dose maintained eugonadal testosterone levels through day 7. The testosterone:estradiol ratios in both groups following the 200-mg injection remained above or at the eugonadal baseline trough day 21. The authors recommend that replacement therapy for hypogonadal men should be 200 mg of testosterone enanthate every 10 to 14 days. A similar dosage would be recommended if testosterone enanthate were to be used as an experimental inhibitor of spermatogenesis (contraceptive agent).     

Rapid synthesis of new DNMT inhibitors derivatives of procainamide

DNA methyltransferases (DNMTs) are responsible for DNA methylation, an epigenetic modification involved in gene regulation. Families of conjugates of procainamide, an inhibitor of DNMT1, were conceived and produced by rapid synthetic pathways. Six compounds resulted in potent inhibitors of the murine catalytic Dnmt3A/3L complex and of human DNMT1, at least 50 times greater than that of the parent compounds. The inhibitors showed selectivity for C5 DNA methyltransferases. The cytotoxicity of the inhibitors was validated on two tumour cell lines (DU145 and HCT116) and correlated with the DNMT inhibitory potency. The inhibition potency of procainamide conjugated to phthalimide through alkyl linkers depended on the length of the linker; the dodecane linker was the best.     

Insulin and insulin-like growth factor I stimulate the proliferation of human ovarian theca-interstitial cells

PURPOSE: We analyzed familial renal oncocytoma to provide a foundation for studies aimed at defining genes involved in the pathogenesis of renal oncocytoma. MATERIALS AND METHODS: We describe 5 families with multiple members affected with renal oncocytoma. Tumors were analyzed pathologically, and affected and nonaffected members were screened clinically and genetically. RESULTS: We identified 12 affected male and 3 affected female (ratio 4:1) individuals in the 5 families. In affected family members renal oncocytomas were often multiple and bilateral. No metastatic disease was observed. Most renal oncocytomas were detected incidentally in asymptomatic individuals or during screening of asymptomatic members of renal oncocytoma families. One identical twin pair was affected with bilateral multiple renal oncocytomas. CONCLUSIONS: Renal oncocytoma may be inherited in some families.     

The epigenetic impact of weaning on craniofacial morphology during growth

Miniature pigs (Sus scrofa) were used as a model to investigate whether the time of weaning (a nongenetic factor) affects skeletal growth rates for both pre- and postweaning time periods. Control litters were weaned at the normal time of 32 days. Two litters were weaned early (at 20 days) and two late (at 46 days). We digitized cranial landmarks from radiographs taken three times a week for a total of 70 days. We used analysis of covariance to test for differences in growth rates between pre- and post-weaning periods, as well as differences in growth rates among treatments. In both the late weaned pigs and the controls, facial length, facial width, basicranial length, and basicranial width growth rates slowed significantly at the time of weaning. However, in the early weaned pigs, there were no significant changes in growth rates for any of the facial or basicranial measurements at weaning. Furthermore, the postweaning rates of growth were different among treatments. One possible implication is that early growth rates could be under tight genetic control while later growth rates can be epigenetically regulated through nutritional changes.     

Application of thermomechanical mass spectroscopy for analysis of molecular and topological structure of rubber

A novel method was applied to study the topological and molecular structures of multicomponent rubber. This method is based on the thermomechanical analysis of a solid polymer. A diblock amorphous structure was found for the studied rubber network. These blocks differ a great deal in their glass transition temperature. The methodology of how to calculate the crosslink density in each block, the molecular weight distribution of the chains between the junctions of the network, and the shares of low‐temperature (soft) and high‐temperature (hard) blocks in a structure of the rubber network were also shown. Based on these data it is possible to calculate the number‐average and weight‐average molecular weight and the polydispersity coefficients of the chains between the junctions of the network. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 490–501, 1999     

Extracellular signal-regulated protein kinases (ERKs) and ERK kinase (MEK) in brain: regional distribution and regulation by chronic morphine

Quantitative blot immunolabeling techniques were used to determine the concentrations of ERK1 (M(r) 44 kDa) and ERK2 (M(r) 42 kDa), the two major extracellular signal-regulated protein kinases, in different regions of rat brain. The aggregate ERK concentrations (ERK1 and ERK2) were relatively high in each of the brain regions studied, ranging from approximately 0.35 ng/microgram protein in cerebellum to approximately 1.2 ng/microgram protein in nucleus accumbens. However, differences in the regional distributions of ERK1 and ERK2 resulted in ratios of their relative abundance that differed by close to 10-fold among the regions studied. The ratios of ERK1 protein to ERK2 protein varied along a rostral-caudal gradient from a low of 0.16 in frontal cortex to a high of 1.5 in pons/medulla. In hypotonic homogenates from regions at either extreme of the gradient, ERK1 and ERK2 were both found to be predominantly (> 80%) soluble. In subcellular fractions prepared from sucrose homogenates of frontal cortex and pons/medulla, both ERK1 and ERK2 were enriched in the synaptosomal and cytosolic fractions, whereas ERK2 was also enriched in the microsomal fraction. By contrast, in subfractions containing purified nuclei, levels of ERK1 and ERK2 were about one-third of those seen in homogenates and, in subfractions enriched in mitochondria, both ERK1 and ERK2 were barely detectable. The catalytic activity of the ERKs paralleled their protein levels in all of the brain regions except the hippocampus, in which the activity and phosphotyrosine content were disproportionately high. As a possible explanation for this apparent disparity, the regional distribution of ERK kinase (MEK), which phosphorylates and activates the ERKs, was also investigated. The levels of immunoreactivity of the M(r) 45 kDa ERK kinase band differed by about threefold among the brain regions, with the highest levels being present in nucleus accumbens, hippocampus, substantia nigra, and caudate/putamen. Therefore, a higher concentration of ERK kinase immunoreactivity did not appear to account for the disproportionate levels of ERK activity and phosphotyrosine content in the hippocampus. Potential regulation of ERK and ERK kinase levels was also investigated in rats subjected to chronic morphine treatment. ERK1 and ERK2 levels were increased selectively in locus coeruleus and caudate/putamen after chronic morphine treatment, whereas ERK kinase immunoreactivity remained unchanged in all of the brain regions analyzed. In summary, the regional differences in ERK and ERK kinase expression and the region-specific regulation of ERK expression suggest that ERK-related signaling may play an important role in CNS function and its adaptive responses.     

Active transport of butyrobetaine and carnitine into isolated liver cells

1. The liver cells lose the major part of their carnitine during the commonly used isolation procedure by the collagenase-perfusion method. 2. The cells take up carnitine and the carnitine precursor butyrobetaine when these substances are added to the medium. The carnitine content of isolated liver cells can increase to about 15 mM with no apparent harm to the cells. 3. The data indicate the existence of a common carrier in the plasma membrane which mediates the uphill transport of both carnitine and butyrobetaine. The carrier has a high affinity for butyrobetaine (Km=0.5 mM) and a lower one for carnitine (Km=5.6 mM). 4. The intracellular butyrobetaine is hydroxylated to carnitine with a rate of approximately 0.33 mumol-g wet weight-1-h-1 which is sufficient to cover the turn over of carnitine in the whole rat. Carnitine is effectively esterified in the liver cells to acetylcarnitine and long-chain acylcarnitines. 5. Both carnitine and acetylcarnitine are released from the cells. The release of both compounds is probably physiological since it was found that acetylcarnitine constitutes a similar fraction of the total acid soluble carnitine both in the blood and liver of the intact rat.     

DNA hypomethylation leads to elevated mutation rates

Genome-wide demethylation has been suggested to be a step in carcinogenesis. Evidence for this notion comes from the frequently observed global DNA hypomethylation in tumour cells, and from a recent study suggesting that defects in DNA methylation might contribute to the genomic instability of some colorectal tumour cell lines. DNA hypomethylation has also been associated with abnormal chromosomal structures, as observed in cells from patients with ICF (Immunodeficiency, Centromeric instability and Facial abnormalities) syndrome and in cells treated with the demethylating agent 5-azadeoxycytidine. Here we report that murine embryonic stem cells nullizygous for the major DNA methyltransferase (Dnmt1) gene exhibited significantly elevated mutation rates at both the endogenous hypoxanthine phosphoribosyltransferase (Hprt) gene and an integrated viral thymidine kinase (tk) transgene. Gene deletions were the predominant mutations at both loci. The major cause of the observed tk deletions was either mitotic recombination or chromosomal loss accompanied by duplication of the remaining chromosome. Our results imply an important role for mammalian DNA methylation in maintaining genome stability.