Hormone-sensitive cyclic GMP-inhibited cyclic AMP phosphodiesterase in rat adipocytes. Regulation of insulin- and cAMP-dependent activation by phosphorylation.

In 32PO4-labeled adipocytes, isoproterenol (ISO) or physiologically relevant concentrations of insulin rapidly increased phosphorylation of a particulate 135-kDa protein which has been identified as a cGMP-inhibited "low Km" cAMP phosphodiesterase (CGI-PDE) by several criteria, including selective immunoprecipitation with anti-CGI-PDE IgG (Degerman, E., Smith, C.J., Tornqvist, H., Vasta, V., Belfrage, P., and Manganiello, V.C. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 533-537). The time courses and concentration dependences for phosphorylation of CGI-PDE by ISO and insulin correlated with CGI-PDE activation in the presence of these agents; effects of ISO were somewhat more rapid than those of insulin. Adenosine deaminase, which metabolizes the adenylate cyclase inhibitor adenosine, also rapidly induced phosphorylation and activation of CGI-PDE. Phenylisopropyladenosine (an adenosine deaminase-resistant adenosine analog) prevented or reversed both adenosine deaminase-stimulated phosphorylation and activation of CGI-PDE (IC50 approximately 0.2 nM). Incubation of adipocytes with 0.1 nM insulin in the presence of ISO rapidly produced 30-200% greater activation and phosphorylation of CGI-PDE than the expected added effects of insulin and ISO individually; both effects preceded the insulin-induced decreases in protein kinase A activity and inhibition of lipolysis. These and other results indicate that CGI-PDE can be phosphorylated at distinct sites and activated by cAMP-dependent and insulin-dependent serine kinase(s), that the activation state of CGI-PDE reflects its relative phosphorylation state, and that synergistic phosphorylation/activation of CGI-PDE may be important in the antilipolytic action of insulin

Force-frequency relationship during dobutamine stress echocardiography predicts exercise tolerance and BNP levels in patients with chronic congestive heart failure

Purpose: D obutamine stress echocardiography (DSE) is widely used to evaluate myocardial contractile reserve; it provides prognostic information in patients with chronic congestive heart failure (CHF). The force?frequency relationship (FFR) is a method for evaluate LV contractility during DSE . The aim of our study is to assess the relationship among FFR, BNP levels, and aerobic exercise capacity in CHF patients. Methods and materials: 37 CHF patients (age 67?8 years, 54% with an ischemic etiology), underwent high dose DSE (up to 40 m g/kg/min). FFR was determined as a ratio between systolic cuff pressure and end-systolic volume (biplane using a Simposon rule) assessed at baseline and peak DSE . BNP levels were determined on blood samples withdrawn at baseline. After a few hours, CHF patients underwent cardiopulmonary exercise test with expired gas measurement. Results: Mean ejection fraction was 32?7% and NHYA class 2.5?0.6. FFR was directly related to peak oxygen consumption (Figure Left), LV ejection fraction (r=0.398, p=0.015) and mitral annulus peak systolic velocity (r=0.428, p=0.013). FFR was inversely related to NYHA class (r=-0.43, p=0.013), LV end-diastolic diameter (r=-0.377, p=0.022), LV intraventricular dyssynchrony (r=-0.394, p=0.016), and BNP levels (Figure Right). At multiple regression analysis, FFR (B=0.502, p= 0.004) and E/Ea ratio (B=-0.336, p=0.044) were the best predictors of exercise tolerance. Conclusions: In patients with stable CHF, impaired myocardial contractility during DSE is related to higher BNP levels and poorer exercise tolerance

Metastatic mixed gestational trophoblastic tumour of the uterus: A case report

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An Algebraic Approach for Decoding Spread Codes

In this paper we study spread codes: a family of constant-dimension codes for random linear network coding. In other words, the codewords are full-rank matrices of size (k x n) with entries in a finite field F_q. Spread codes are a family of optimal codes with maximal minimum distance. We give a minimum-distance decoding algorithm which requires O((n-k)k^3) operations over an extension field F_{q^k}. Our algorithm is more efficient than the previous ones in the literature, when the dimension k of the codewords is small with respect to n. The decoding algorithm takes advantage of the algebraic structure of the code, and it uses original results on minors of a matrix and on the factorization of polynomials over finite fields

Receptor-Mediated Gonadotropin Action in Ovary

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65826/1/j.1432-1033.1979.tb12873.x.pd

Association between a variation in the phosphodiesterase 4D gene and bone mineral density

BACKGROUND: Fragility fractures caused by osteoporosis are a major cause of morbidity and mortality in aging populations. Bone mineral density (BMD) is a useful surrogate marker for risk of fracture and is a highly heritable trait. The genetic variants underlying this genetic contribution are largely unknown. METHODS: We performed a large-scale association study investigating more than 25,000 single nucleotide polymorphisms (SNPs) located within 16,000 genes. Allele frequencies were estimated in contrasting DNA pools from white females selected for low (<0.87 g/cm(2), n = 319) and high (> 1.11 g/cm(2), n = 321) BMD at the lumbar spine. Significant findings were verified in two additional sample collections. RESULTS: Based on allele frequency differences between DNA pools and subsequent individual genotyping, one of the candidate loci indicated was the phosphodiesterase 4D (PDE4D) gene region on chromosome 5q12. We subsequently tested the marker SNP, rs1498608, in a second sample of 138 white females with low (<0.91 g/cm(2)) and 138 females with high (>1.04 g/cm(2)) lumbar spine BMD. Odds ratios were 1.5 (P = 0.035) in the original sample and 2.1 (P = 0.018) in the replication sample. Association fine mapping with 80 SNPs located within 50 kilobases of the marker SNP identified a 20 kilobase region of association containing exon 6 of PDE4D. In a second, family-based replication sample with a preponderance of females with low BMD, rs1498608 showed an opposite relationship with BMD at different sites (p = 0.00044-0.09). We also replicated the previously reported association of the Ser37Ala polymorphism in BMP2, known to interact biologically with PDE4D, with BMD. CONCLUSION: This study indicates that variants in the gene encoding PDE4D account for some of the genetic contribution to bone mineral density variation in humans. The contrasting results from different samples indicate that the effect may be context-dependent. PDE4 inhibitors have been shown to increase bone mass in normal and osteopenic mice, but up until now there have been no reports implicating any member of the PDE4 gene family in human osteoporosis