Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease

Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD.     

Design,synthesis, tandem mass spectrometric sequencing and biological activity of NGF mimetics

Nine low molecular weight nerve growth factor (NGF)-like peptides have been designed to mimic the putative receptor-binding epitope of NGF defined by two β-hairpin loops. Eight different spacers were used as variable links between the β-loop amino acid residues, which from mutagenesis experiments were found to play an important role in the biological activity of NGF. These spacers were amino acids, natural or non-natural, differing in length (5–13 Å) and polarity. The peptides were synthesized via the Fmoc solid-phase peptide synthesis and purified by reversed-phase HPLC. Their primary sequences were analyzed by a combination of automated Edman degradation and mass spectrometry. The peptides were tested using two different biological assays, the fibre outgrowth from chick embryonic sympathetic ganglia and the PC 12 cell differentiation assay. Weak antagonistic effects could be observed for some peptides. © Munksgaard 1996.     

MALIGNANT HYPERTHERMIA IN BELGIAN LANDRACE PIGS RESTED OR EXCERCISED BEFORE EXPOSURE TO HALOTHANE

Thirteen of 31 Belgian Landrace pigs developed malignant hyperthermia(MH) after breathing halothane. A short period of exercise 1h before the administration of the triggering agent increasedthe incidence of the syndrome to 100% in eight similar pigs.Clinical symptoms were more marked and developed more rapidlyin the exercised pigs. All the reacting pigs became typicallyacidotic, developed rigor and died. Serum Na⁺, K+, Ca2⁺, c.p.k.,l.d.h. and protein concentrations were increased to a variableextent during the reaction and there was an increase in p.c.v.also. No hyper-glycaemia was detected in pigs which were restedbefore receiving halothane. Four of the eight exercised pigsbecame markedly hyperglycaemic and plasma noradrenaline increasedto higher values. Phosphocreatine and ATP decreased to low valuesand lactate increased in the muscles of all pigs which reacted.At the time of death, muscle glycogen had decreased significantlyin the rested, but not in the exercised, MH pigs. ^*Present address: ARC Meat Research Institute, Langford, BristolBS18 7DY.     

Arachidonic acid facilitates experimental chronic osteomyelitis in rats.

Arachidonic acid was used as a facilitating agent in experimental rat Staphylococcus aureus osteomyelitis and compared with the more commonly used agent, sodium morrhuate. The injection of arachidonic acid or sodium morrhuate and S. aureus into rat tibiae caused increased quantitative bacterial bone counts, gross bone pathology, roentgenographic changes, and weight loss. The doses required to produce these changes appeared to be lower for arachidonic acid.     

Investigation of the ecology of Soldado virus on Puffin Island, North Wales.

The prevalence of Soldado (SOL) virus and SOL virus antibodies was investigated on immature sea birds and the argasid tick Ornithodoros (Alectorobius) maritimus collected on Puffin Island, North Wales. No SOL virus was recovered from 133 bird sera, but 2 of the birds exhibited neutralizing antibodies against SOL virus. Nine of 27 tick pools (226 individuals) and 34 of 173 ticks tested individually proved to be infected with SOL virus.     

Metabolism of xylitol in dental plaque

Abstract – It has been reported previously that xylitol added to glucose used to challenge dental plaque in vivo caused a reduced acid formation. The aim of the present study was to approach the mechanism by which xylitol may affect glucose catabolism in plaque bacteria. Suspensions of freshly collected 4-day-old plaque bacteria were ineubated, one batch with labeled xylitol, one with labeled glucose, in vitro at 37°C. Samples of cells were taken out at time intervals, collected on paper discs and subjected to scintillation counting. It was observed that the plaque bacteria took up xylitol, the uptake increasing with incubation of more than 3–4 h, whereas the same cells took up glucose immediately. Cells which had taken up xylitol were extracted with boiling water, extracts concentrated and applied on thin-layer chromatography sheets. A radioactive component with mobility like xylitol-5-phosphate was isolated from the cell extracts, and also a component where labeled xylitol was associated with macromolecules. It is suggested that the accumulation of the metabolities within the cells inhibits glycolysis.     

Strain-specific effects of rosiglitazone on bone mass, body composition, and serum insulin-like growth factor-I

Activation of peroxisome proliferator activated receptor-gamma (PPARG) is required for the differentiation of marrow mesenchymal stem cell into adipocytes and is associated with the development of age-related marrow adiposity in mice. Thiazolidinediones are agonists for PPARG and have a heterogeneous effect on bone mineral density (BMD). We postulated that genetic determinants influence the skeletal response to thiazolidinediones. We examined the effects of rosiglitazone (3 mg/kg . d for 8 wk) on BMD, body composition, and serum IGF-I in adult female mice from four inbred strains. C3H/HeJ mice showed the most significant response to treatment, exhibiting decreased femoral and vertebral BMD, reduced distal femoral bone volume fraction and a decrease in serum IGF-I. In DBA/2J, there were no changes in femoral BMD or bone volume fraction, but there was a decrease in vertebral BMD. C57BL/6J mice showed increases in marrow adiposity, without associated changes in trabecular bone volume; the skeletal effects from rosiglitazone in A/J mice were minimal. No association between trabecular bone volume and marrow adiposity was found. The effect of rosiglitazone on gene expression in the femur was then examined in the C3H/HeJ and C57BL/6J strains by microarray. Increased gene expression was observed in the PPARG signaling pathway and fatty acid metabolism in both C3H/HeJ and C57BL/6J, but a significant down-regulation of genes associated with cell cycle was noted only in the C3H/HeJ strain. The divergent skeletal responses to rosiglitazone in this study suggest the existence of a strong genetic background effect.