Effects of GH on urea,glucose and lipid metabolism,and insulin sensitivity during fasting in GH-deficient patients

Fasting-related states of distress pose major health problems, and growth hormone (GH) plays a key role in this context. The present study was designed to assess the effects of GH on substrate metabolism and insulin sensitivity during short-term fasting. Six GH-deficient adults underwent 42.5 h of fasting on two occasions, with and without concomitant GH replacement. Palmitate and urea fluxes were measured with the steady-state isotope dilution technique after infusion of [9,10-3H]palmitate and [13C]urea. During fasting with GH replacement, palmitate concentrations and fluxes increased by 50% [palmitate: 378 +/- 42 (GH) vs. 244 +/- 12 micromol/l, P < 0.05; palmitate: 412 +/- 58 (GH) vs. 276 +/- 42 microM, P = 0.05], and urea turnover and excretion decreased by 30-35% [urea rate of appearance: 336 +/- 22 (GH) vs. 439 +/- 43 micromol. kg-1. h-1, P < 0.01; urea excretion: 445 +/- 43 (GH) vs. 602 +/- 74 mmol/24 h, P < 0.05]. Insulin sensitivity (determined by a euglycemic hyperinsulinemic clamp) was significantly decreased [M value: 1.26 +/- 0.06 (GH) vs. 2.07 +/- 0.22 mg. kg-1. min-1, P < 0.01] during fasting with GH replacement. In conclusion, continued GH replacement during fasting in GH-deficient adults decreases insulin sensitivity, increases lipid utilization, and conserves protein.     

Reduced free IGF-I and increased IGFBP-3 proteolysis in Turner syndrome: modulation by female sex steroids

The bioactivity of the growth hormone-insulin-like growth factor (IGF) system is reduced in Turner syndrome and may explain the reduction seen in final height. We compared levels of free and total IGF-I, immunoreactive and Western ligand blot IGF-binding protein (IGFBP)-3, and IGFBP-3 proteolysis in women with Turner syndrome (n = 23) before (T(B)) and during 6 mo treatment with 17beta-estradiol and norethisterone. An age-matched group of controls (n = 24) was included. Total IGF-I and immunoreactive levels of IGFBP-3 were comparable in T(B) and controls, whereas free IGF-I (P = 0.02) in T(B) was less than in controls. Western ligand blotting (WLB)-IGFBP-3 was significantly lower in T(B) than in controls (P = 0.0005). Accordingly, IGFBP-3 proteolysis was greater in Turner syndrome (P = 0.001). Female sex steroid treatment increased WLB-IGFBP-3 (P = 0.0005), whereas immunoreactive IGFBP-3 and IGFBP-3 proteolysis were normalized (P = 0.004). Free IGF-I remained unchanged (P = 0.8), with a tendency toward a decrease in total IGF-I (P = 0.1). In conclusion, despite normal total IGF-I and immunoreactive IGFBP-3, free serum IGF-I is less and IGFBP-3 proteolysis is greater in Turner syndrome than in controls. During sex steroid treatment, IGFBP-3 proteolysis normalized, without any change in free IGF-I.     

The genomic organization and evolution of the natural killer immunoglobulin-like receptor (KIR) gene cluster

Natural killer (NK) immunoglobulin-like receptors (KIRs) are a family of polymorphic receptors which interact with specific motifs on HLA class I molecules and modulate NK cytolytic activity. In this study, we analyzed a recently sequenced subgenomic region on chromosome 19q13.4 containing eight members of the KIR receptor repertoire. Six members are clustered within a 100-kb continuous sequence. These genes include a previously unpublished member of the KIR gene family 2DS6, as well as 2DL1, 2DL4, 3DL1, 2DS4, 3DL2, from centromere to telomere. Two additional KIR genes, KIRCI and 2DL3, which may be located centromeric of this cluster were also analyzed. We show that the KIR genes have undergone repeated gene duplications. Diversification between the genes has occurred postduplication primarily as a result of retroelement indels and gene truncation. Using pre- and postduplication Alu sequences identified within these genes as evolutionary molecular clocks, the evolution and duplication of this gene cluster is estimated to have occurred 30–45 million years ago, during primate evolution. A proposed model of the duplication history of the KIR gene family leading to their present organization is presented. Received: 25 November 1999 / Revised: 10 January 2000     

Mutational spectrum in the cardioauditory syndrome of Jervell and Lange-Nielsen

Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive syndrome characterised by profound congenital sensorineural deafness and prolongation of the QT interval on the electrocardiogram, representing abnormal ventricular repolarisation. In a study of ten British and Norwegian families with JLNS, we have identified all of the mutations in the KCNQ1 gene, including two that are novel. Of the nine mutations identified in this group of 10 families, five are nonsense or frameshift mutations. Truncation of the protein proximal to the recently identified C-terminal assembly domain is expected to preclude assembly of KCNQ1 monomers into tetramers and explains the recessive inheritance of JLNS. However, study of a frameshift mutation, with a dominant effect phenotypically, suggests the presence of another assembly domain nearer to the N-terminus.     

Axial and appendicular pneumaticity in Archaeopteryx

From the time of its discovery in 1860 to this day Archaeopteryx has been essential to our understanding of avian evolution. Despite the great diversity of plesiomorphic avialan (sensu Gauthier 1986) taxa discovered within the last decade, Archaeopteryx remains the most basal avialan taxon. A very unusual feature of extant birds is their lung structure, in which air diverticulae penetrate the bones. This has previously been reported in Archaeopteryx as well, in the cervical vertebrae of the Berlin specimen and in an anterior thoracal vertebra of the Eichstätt specimen. This indicates the presence of a cervical air sac. We show that the London specimen also has pneumatized anterior thoracal vertebrae, and, thus, that this feature was present in the most archaic avialans, as the London and Eichstätt specimens are different species. Furthermore, the pelvis of the London specimen shows clear signs of the presence of an abdominal air sac, indicating that at least two of the five air sacs present in modern birds were also present in Archaeopteryx. Evidence of pubic pneumaticity was also found in the same position in some extant ratites.     

Membrane proteins PmpG and PmpH are major constituents of Chlamydia trachomatis L2 outer membrane complex

The outer membrane complex of Chlamydia is involved in the initial adherence and ingestion of Chlamydia by the host cell. In order to identify novel proteins in the outer membrane of Chlamydia trachomatis L2, proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. By silver staining of the protein profile, a major protein doublet of 100-110 kDa was detected. In-gel tryptic digestion and matrix-assisted laser desorption/ionization mass spectrometry identified these proteins as the putative outer membrane proteins PmpG and PmpH.     

Resuspension studies in cylindrical microcosms: Effects of stirring velocity on the dynamics of redox sensitive elements in a coastal sediment

Effects of resuspension on the release of dissolved, redox sensitive elements (Fe, Mn) was studied in cylindrical microcosms. Effects from changing water stirring velocity in sediment pools were evaluated through measurements of pore water profiles of dissolved Mn, Fe and redox potential. Mn was a good natural marker to follow such effects. At current velocities below the threshold velocity for resuspension (37 cm s-1), Mn release rates to overlying water were 100 times higher compared to steady-state values. Pulse increases in Mn concentration were the result of convective currents inside flow chambers. These results were strongly supported by measurements of Eh profiles in the sediment pore water. Furthermore, impacts from increasing stirring velocity were found down to 1.9 cm depth below the resuspended layer of sediment.     

Role of Mannose-Binding Lectin Deficiency in HIV-1 and Schistosoma Infections in a Rural Adult Population in Zimbabwe

Background

Polymorphism in the MBL2 gene lead to MBL deficiency, which has been shown to increase susceptibility to various bacterial, viral and parasitic infections. We assessed role of MBL deficiency in HIV-1 and schistosoma infections in Zimbabwean adults enrolled in the Mupfure Schistosomiasis and HIV Cohort (MUSH Cohort).

Methods

HIV-1, S. haematobium and S. mansoni infections were determined at baseline. Plasma MBL concentration was measured by ELISA and MBL2 genotypes determined by PCR. We calculated and compared the proportions of plasma MBL deficiency, MBL2 structural variant alleles B (codon 54A>G), C (codon 57A>G), and D (codon 52T>C) as well as MBL2 promoter variants -550(H/L), -221(X/Y) and +4(P/Q) between HIV-1 and schistosoma co-infection and control groups using Chi Square test.

Results

We assessed 379 adults, 80% females, median age (IQR) 30 (17–41) years. HIV-1, S. haematobium and S. mansoni prevalence were 26%, 43% and 18% respectively in the MUSH baseline survey. Median (IQR) plasma MBL concentration was 800μg/L (192-1936μg/L). Prevalence of plasma MBL deficiency was 18% with high frequency of the C (codon 57G>A) mutant allele (20%). There was no significant difference in median plasma MBL levels between HIV negative (912μg/L) and HIV positive (688μg/L), p = 0.066. However plasma MBL levels at the assay detection limit of 20μg/L were more frequent among the HIV-1 infected (p = 0.007). S. haematobium and S. mansoni infected participants had significantly higher MBL levels than uninfected. All MBL2 variants were not associated with HIV-1 infection but promoter variants LY and LL were significantly associated with S. haematobium infection.

Conclusion

Our data indicate high prevalence of MBL deficiency, no evidence of association between MBL deficiency and HIV-1 infection. However, lower plasma MBL levels were protective against both S. haematobium and S. mansoni infections and MBL2 promoter and variants LY and LL increased susceptibility to S. haematobium infection.