Three methyl 11-(N-acryloyl-N-alkylamino)undecanoates were synthesized from acryloyl chloride and amino-or alkylaminoundecanoic acid esters. These compounds were telomerized in the presence of 1-dodecanethiol as telogen to yield telomers with molecular weight lower than 5000. These telomers are likely to generate HIV inhibitor polyanions with good biocompatibility. The K/Kt value was assessed from a kinetic study of the telomerization reaction. NMR spectroscopy analysis indicates that the polymerization degree DP n are in good agreement with expectation for methyl 11-(N-acryloylamino)undecanoate. However, they were lower than expected for methyl 11-(N-acryloyl-N-alkylamino)undecanoate. 相似文献
Neonatal diabetes can either remit and hence be transient or else may be permanent. These two phenotypes were considered to be genetically distinct. Abnormalities of 6q24 are the commonest cause of transient neonatal diabetes (TNDM). Mutations in KCNJ11, which encodes Kir6.2, the pore-forming subunit of the ATP-sensitive potassium channel (K(ATP)), are the commonest cause of permanent neonatal diabetes (PNDM). In addition to diabetes, some KCNJ11 mutations also result in marked developmental delay and epilepsy. These mutations are more severe on functional characterization. We investigated whether mutations in KCNJ11 could also give rise to TNDM. We identified the three novel heterozygous mutations (G53S, G53R, I182V) in three of 11 probands with clinically defined TNDM, who did not have chromosome 6q24 abnormalities. The mutations co-segregated with diabetes within families and were not found in 100 controls. All probands had insulin-treated diabetes diagnosed in the first 4 months and went into remission by 7-14 months. Functional characterization of the TNDM associated mutations was performed by expressing the mutated Kir6.2 with SUR1 in Xenopus laevis oocytes. All three heterozygous mutations resulted in a reduction in the sensitivity to ATP when compared with wild-type (IC(50) approximately 30 versus approximately 7 microM, P-value for is all <0.01); however, this was less profoundly reduced than with the PNDM associated mutations. In conclusion, mutations in KCNJ11 are the first genetic cause for remitting as well as permanent diabetes. This suggests that a fixed ion channel abnormality can result in a fluctuating glycaemic phenotype. The multiple phenotypes associated with activating KCNJ11 mutations may reflect their severity in vitro. 相似文献
Four multicentre double blind trials (two studies comparing placebo to a marketed activating drug and two comparing placebo to a new drug with central adrenergic modulating properties) were pooled, totalling 77 placebo Ss, 30 reference drug Ss and 73 study drug Ss. The AMDP-4 and -5 scales were filled out at day 0 and 7 by trained raters. Four statistical analyses were performed on the pre- vs. postdrug differences: an analysis of variance, a principal components factor analysis, a discriminant analysis and a cluster analysis. The results indicate that 9 out of the 14 AMDP factor scores significantly decrease within 1 week while the factor Mania-Agitation increases, without differences between both active compounds; on the item level, the "inhibition of drive" is specifically improved by the study drug; the discriminant analysis confirms that the two most improved items are "Inhibition of drive" and "Hopelessness". Three factor scores significantly improve on placebo (Depression, Retardation, Psycho-organic Symptoms), which points to the necessity of placebo-controlled studies in clinical trials of new drugs. 相似文献
Six classes of students attending private parochial high schools were matched according to geographic and grade level variables and were randomly assigned as intact groups to view either a film concerning wife abuse or a neutral control film. The experimental film had no significant impact on attitude ratings given for the two most common student-generated situations of abuse: the intoxicated husband and the unfaithful wife. Correlational assessments between demographic variables and attitude ratings revealed that greater suspicion of abuse was associated with higher justifiability ratings for the intoxicated husband situation. Estimations of higher frequencies of spouse abuse were associated with higher justifiability ratings for the unfaithful wife situation. Results are discussed in light of current wife abuse education programs and prevention strategies. 相似文献
Many rural veterans receive care in community settings but could benefit from VA services for certain needs, presenting an opportunity for coordination across systems. This article details the Collaborative Systems of Care (CSC) program, a novel, nurse-led care coordination program identifying and connecting veterans presenting for care in a Federally Qualified Health Center to VA behavioral health and other services based upon the veteran’s preferences and eligibility. The CSC program systematically identifies veteran patients, screens for common behavioral health issues, explores VA eligibility for interested veterans, and facilitates coordination with VA to improve healthcare access. While the present program focuses on behavioral health, there is a unique emphasis on assisting veterans with the eligibility and enrollment process and coordinating additional care tailored to the patient. As VA expands its presence in community care, opportunities for VA-community care coordination will increase, making the development and implementation of such interventions important.
PurposeWe evaluated the prognostic value of 10 putative tumor markers by immunohistochemistry in a large multi-institutional cohort of patients with locally advanced urothelial cancer of the bladder (UCB) with the aim to validate their clinical value and to harmonize protocols for their evaluation.Materials and MethodsPrimary tumor specimens from 576 patients with pathologic (p)T3 UCB were collected from 24 institutions in North America and Europe. Three replicate 0.6-mm core diameter samples were collected for the construction of a tissue microarray (TMA). Immunohistochemistry (IHC) for 10 previously described tumor markers was performed and scored at 3 laboratories independently according to a standardized protocol. Associations between marker positivity and freedom from recurrence (FFR) or overall survival (OS) were analyzed separately for each individual laboratory using Cox regression analysis.ResultsThe overall agreement of the IHC scoring among laboratories was poor. Correlation among the 3 laboratories varied across the 10 markers. There was generally a lack of association between the individual markers and FFR or OS. The number of altered cell cycle regulators (p53, Rb, and p21) was associated with increased risk of cancer recurrence (P < 0.032). There was no clear pattern in the relationship between the percentage of markers altered in an 8-marker panel and FFR or OS.ConclusionsThis large international TMA of locally advanced (pT3) UCB suggests that altered expression of p53, Rb, and p21 is associated with worse outcome. However this study also highlights limitations in the reproducibility of IHC even in the most expert hands. 相似文献