Functionalization of poly(ethylene glycol) and monomethoxy-poly(ethylene glycol)

Simple methods are described for the substitution of poly(ethylene glycol) and monomethoxy-poly(ethylene glycol) substitution. Affinity ligands, coenzymes, or enzymes can be covalently attached to the substitution product or they can be used as liquid ionexchangers.     

Proteomic identification of the involvement of the mitochondrial rieske protein in epilepsy

PURPOSE: Kindled seizures are widely used to model epileptogenesis, but the molecular mechanisms underlying the attainment of kindling status are largely unknown. Recently we showed that achievement of kindling status in the Sprague-Dawley rat is associated with a critical developmental interval of 25 +/- 1 days; the identification of this long, well-defined developmental interval for inducing kindling status makes possible a dissection of the cellular and genetic events underlying this phenomenon and its relation to normal and pathologic brain function. METHODS: By using proteomics on cerebral tissue from our new rat kindling model, we undertook a global analysis of protein expression in kindled animals. Some of the identified proteins were further investigated by using immunohistochemistry. RESULTS: We report the identification of a modified variant of the Rieske iron-sulfur protein, a component of the mitochondrial cytochrome bc1 complex, whose isoelectric point is shifted toward more alkaline values in the hippocampus of kindled rats. By immunohistochemistry, the Rieske protein is well expressed in the hippocampus, except in the CA1 subfield, an area of selective vulnerability to seizures in humans and animal models. We also noted an asymmetric, selective expression of the Rieske protein in the subgranular neurons of the dorsal dentate gyrus, a region implicated in neurogenesis. CONCLUSIONS: These results indicate that the Rieske protein may play a role in the response of neurons to seizure activity and could give important new insights into the molecular pathogenesis of epilepsy.     

Evolution of resistance under insecticide selection pressure in Culex pipiens quinquefasciatus (Diptera, Culicidae) from Martinique

Population surveys of Culex pipiens quinquefasciatus carried out in 1991 and 1999 were compared with data collected in 1990 before the beginning of the control program against this mosquito. Larval samples collected in 1999 displayed resistance to the four tested insecticides: permethrin, propoxur, temephos, and chlorpyrifos. Temephos resistance ratio at LC50 (RR50) ranged between 8.1- and 42-fold compared with 2.9- and 4.6-fold in 1990, and chlorpyrifos RR50 ranged between 8.6- and 123-fold compared with 6.4- and 19-fold in 1990. This increased resistance to organophosphorus insecticides was associated with a sharp decrease of susceptible genotypes at two loci (Ester and ace-1), as well as to an allele replacement at the Ester locus.     

An increasing trend in the incidence of type 1 diabetes mellitus in children aged 0-14 years in Romania--ten years (1988-1997) EURODIAB study experience

AIM: To assess the incidence of type 1 diabetes mellitus (DM1) in Romanian children aged 0-14 years using EURODIAB Study methodology. METHODS: Data were collected for a 10-year interval (1988-1997) for the whole country, using the capture-recapture method. RESULTS: We registered 1,418 newly diagnosed patients. The mean total incidence rate was 3.051/100,000/year. There was a wide geographic variation (6.71-fold) between the highest and the lowest incidence rates in different districts. We noticed a progressive increase of age-specific incidence rates from 1.43/100,000/year for the 0-4 year age subgroup to 4.37/100,000/year (10-14 years). The annual mean incidence rate rose from 1.91/100,000/year (1988) to 3.94/100,000/year (1996). CONCLUSIONS: Romania is one of the European countries with the lowest incidence rates (3.051/100,000/year) for DM1 in children. There was an evident increasing trend of DM1 incidence in children between 1988 and 1997, with an annual increase of 7.57%.     

High follicle-stimulating hormone levels should not necessarily lead to the exclusion of subfertile patients from treatment

OBJECTIVE: To determine ongoing pregnancy rates in subfertile patients with elevated FSH levels and regular cycles and to assess whether or not it is justified to exclude such patients from treatment on the basis of elevated FSH levels alone. DESIGN: Retrospective follow-up study. SETTING: Tertiary fertility center. PATIENT(S): One hundred twenty-two patients with normal FSH levels <10.0 IU/L, 126 with FSH between 10.0 and 15.0 IU/L, and 53 with FSH levels >15.0 IU/L, all having regular cycles and belonging to a general subfertility population. INTERVENTION(S): Follow-up. MAIN OUTCOME MEASURE(S): Overall and treatment-independent and treatment-dependent ongoing pregnancy rates and time to ongoing pregnancy. RESULT(S): Overall ongoing pregnancy rates declined from 65% in the normal FSH group to 47%, and 28% in the respective elevated FSH groups. However, when adjusting for differences in age and whether or not treatment was applied, this declining trend became inconsistent for both treatment-independent and treatment-dependent ongoing pregnancy rates. Only when FSH levels exceeded 20 IU/L was a clear fall in ongoing pregnancy rate observed, independent of age. In a Cox regression analysis, FSH seemed significantly associated with the outcome time to overall ongoing pregnancy (odds ratio = 0.94, 95% confidence interval, 0.88-0.99), but after adjusting for age and being on treatment or not this significance disappeared (odds ratio = 0.97, 95% confidence interval, 0.91-1.01). CONCLUSION(S): The contribution of FSH in the initial evaluation of subfertile couples is restricted to counseling patients on the probability of having lower chances of conceiving. It does not seem justified to exclude patients with normal regular cycles from treatment on the basis of the FSH value alone.     

Analysis of the vitamin D receptor gene sequence variants in type 1 diabetes

Vitamin D is known to modulate the immune system, and its administration has been associated with reduced risk of type 1 diabetes. Vitamin D acts via its receptor (VDR). Four single nucleotide polymorphisms (SNPs) of the VDR gene have been commonly studied, and evidence of association with type 1 diabetes has been reported previously. We sequenced the VDR gene region and developed its SNP map. Here we analyzed association of the 98 VDR SNPs in up to 3,763 type 1 diabetic families. First, we genotyped all 98 SNPs in a minimum of 458 U.K. families with two affected offspring. We further tested eight SNPs, including four SNPs associated with P < 0.05 in the first set and the four commonly studied SNPs, in up to 3,305 additional families from the U.K., Finland, Norway, Romania, and U.S. We only found weak evidence of association (P = 0.02-0.05) of the rs4303288, rs12721366, and rs2544043 SNPs. We then tested these three SNPs in an independent set of 1,587 patients and 1,827 control subjects from the U.K. and found no evidence of association. Overall, our results indicate that common sequence variation in the VDR gene has no major effect in type 1 diabetes in the populations tested.     

Surveillance for retinopathy of prematurity in a Copenhagen high-risk sample 1999-2001. Has progress reached a plateau?

PURPOSE: As part of a current quality control to evaluate ophthalmic findings in two combined central Copenhagen neonatology centers for birth years 1999-2001, and to compare the selected sample with data of the national register for childhood visual impairment. METHODS: In a prospective design to report on 372 infants mainly under regular surveillance for retinopathy of prematurity (ROP) in the stratified functional unit made up by the neonatal wards of Righospitalet (RH) and Hvidovre Hospital (HH). The median neonate under ophthalmic surveillance in the two wards (screening limits usually 32 weeks/1750 g) was given by gestational age (GA) and birthweight (BW) values of 27.3 weeks/907 g and 30.3 weeks/1420 g. respectively. Feedback regarding outcome was secured for those transferred to regional centres. RESULTS: The overall frequency of ROP was 38.5% in the RH (n=252) and 10.8% in the HH sample (n=120). From a peak share above 60% in those <26 weeks/750 g at delivery, the incidence of ROP showed a regular decrease with decreasing immaturity. The centralized retinal ablation therapy for advanced ROP was given to a total of 29, with birth year 2001 unexpectedly showing a peak of 17 cases. Seven of the 29 children treated are now in the register for visually impaired, mainly due to low vision. Fourteen of the 29 had been very small for gestational age. CONCLUSIONS: Supported also by recent regional Danish data, the apparent progress in the fight against ROP over many years seems to have come to a halt. Except for the continued increased survival of extremely preterm babies we have no obvious neonatological indication to explain the suggested 'adverse' trends.