Level of p75 receptor expression in sensory ganglia is modulated by NGF level in the target tissue

Neurotrophins play an essential role in sensory development by providing trophic support to neurons that innervate peripheral targets. Nerve growth factor (NGF), neurotrophin-3, neurotrophin-4, and brain-derived neurotrophin exert their survival effect by binding to two transmembrane receptor types: trk receptors, which exhibit binding specificity, and the p75NTR receptor, which binds all neurotrophins. To determine how target-derived neurotrophins affect sensory neuron development and function, we used transgenic mice that overexpress NGF in the skin to examine the impact of NGF overexpression on receptor expression. Previous studies of trk expression in trigeminal ganglia of adult NGF transgenics showed that the percentage of trkA neurons doubled and their number increased fivefold. The present study focused on the p75 receptor and shows that the percentage of neurons expressing p75NTR also increase in NGF ganglia, but only by 10%. This increase did not encompass the small, BS-IB-4 isolectin-positive cells as they remained p75 negative in transgenic ganglia. Interestingly, levels of trkA protein were not increased on a per-cell level, whereas levels of p75NTR increased nearly threefold. These results show that in sensory systems, target-derived NGF modulates the level of p75NTR receptor expression, and in so doing, may act to regulate the formation of functional receptor complexes and subsequent trophic action.     

Orthognathic surgery effects on maxillary growth in patients with vertical maxillary excess

Patients with acute renal failure in the intensive care unit have high in-hospital mortality. In this setting, decision making with regard to the initiation or discontinuation of dialysis by physicians, patients, and families is challenging because of the desire of all for the patient to recover while sparing unnecessary suffering. Decision making can be facilitated by knowledge of outcomes of the treatment of such patients in the medical literature. This knowledge assists nephrologists to distinguish those patients whose clinical situation indicates a more favorable prognosis from those whose prognosis is uncertain or definitely poor even with dialysis. This information, combined with consideration of relevant ethical guidelines, provides a framework for nephrologists to make decisions that are evidence based and ethically sound. We present and discuss two cases to show the application of evidence-based medicine and ethical considerations to decision making for patients with acute renal failure in the intensive care unit.     

Synthesis and structural determination of stereoisomers of muscarinic ligands of the (3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicycloalkane type

Methods for the synthesis of each of the four stereoisomers of 6-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]oc tane (10, 11, 12, and 13) and 3-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[2.2.1]he ptane (18, 19, 20, and 21), and the two stereoisomers of 3-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[2.2.2]oc tane (27 and 28) were developed. The relative configuration of the compounds was determined on the basis of previously described 1H NOE experiments, and the absolute configuration of 6-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]oc tanes (10, 11, 12, and 13) and 3-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[2.2.2]oc tane (27 and 28) was determined by single crystal X-ray crystallography. Optical purity was determined by capillary electrophoresis (CE) using chiral selectors as trimethyl-beta-cyclodextrin and heparin dissolved in the running buffer. All the 3-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicycles had low nanomolar affinity for muscarinic receptors as determined by displacement of radiolabelled oxotremorine-M (3H-Oxo-M) and pirenzepine (3H-Pz) from cortical rat brain homogenates. The binding assay discriminated between diastereomers, but only a minor degree of enantioselectivity was observed in the binding assays.     

Does bilateral internal thoracic artery grafting increase surgical risk in diabetic patients?

BACKGROUND: The purpose of this study was to determine whether, with appropriate techniques, diabetic patients could benefit from the advantages of double internal thoracic artery (ITA) coronary bypass without an increased hospital risk. METHODS: Between January 1990 and December 1996, 207 consecutive diabetic patients underwent coronary artery bypass graft operations. In 74 patients both arteries (bilateral ITA group) were used, whereas 133 patients received one ITA and vein grafts or vein grafts alone (nonbilateral group). Patients in the bilateral ITA group were younger (p<0.0001), predominantly male (p<0.0001), and were operated on more electively. The internal thoracic arteries were harvested by skeletonization without electrocautery, and strict glycemic control was pursued. RESULTS: No death was observed in the bilateral ITA group, whereas 7 patients died in the nonbilateral ITA group (p<0.05). Deep sternal wound infection was observed in 2 patients in the nonbilateral ITA group (1.5%) and in none of the bilateral ITA group (p = NS). There was no significant difference in the morbidity rate between the two groups except for greater blood losses in the bilateral ITA group. CONCLUSION: Double ITA coronary revascularization in young diabetic patients was performed without increased morbidity and mortality. The low rate of sternal wound infections may be related to ITA harvesting by a skeletonization technique, but larger studies are required to confirm these data.     

Nucleotide sequence of both genomic RNAs of a North American tobacco rattle virus isolate

The complete sequence of a North American tobacco rattle virus (TRV) isolate, 'Oregon yellow' (ORY), was determined from cDNA and RT-PCR clones derived from the two genomic RNAs of this isolate. The RNA-1 is 6790 bases and RNA-2 is 3261 bases. The sequence of TRV-ORY RNA-1 was similar to RNA-1 to TRV isolate SYM, and differs in 48 nucleotides. TRV-ORY RNA-1 was one base shorter than--SYM, and had 47 base substitutions resulting in 12 amino acid substitutions of which 4 were conservative. The RNA-2 of TRV-ORY was distinct from RNA-2 of other characterized TRV isolates and contained three open reading frames (ORFs) that could potentially code for proteins of MW 22.4 kDa, 37.6 kDa and 17.9 kDa. Based on the homology of the predicted amino acid sequence with those of other tobraviruses. ORF1 of RNA-2 encodes the coat protein (CP). The protein sequence of ORF2 had regions of limited similarity with those of ORF2 of two other TRV isolates and pea early browning tobravirus. The ORF3 was unique to TRV-ORY. Phylogenetic analysis of tobravirus CPs indicated that TRV-ORY was most closely related to pepper ringspot tobravirus and TRV-TCM. The relationship of tobravirus CPs to other rod-shaped tubular plant viruses is also discussed.