Features of MotA proton channel structure revealed by tryptophan-scanning mutagenesis.

The MotA protein of Escherichia coli is a component of the flagellar motors that functions in transmembrane proton conduction. Here, we report several features of MotA structure revealed by use of a mutagenesis-based approach. Single tryptophan residues were introduced at many positions within the four hydrophobic segments of MotA, and the effects on function were measured. Function was disrupted according to a periodic pattern that implies that the membrane-spanning segments are alpha-helices and that identifies the lipid-facing parts of each helix. The results support a hypothesis for MotA structure and mechanism in which water molecules form most of the proton-conducting pathway. The success of this approach in studying MotA suggests that it could be useful in structure-function studies of other integral membrane proteins.     

United states non-Hodgkin's lymphoma surveillance by occupation 1984-1989: A twenty-four state death certificate study

Death certificates from 23,890 male and female non-Hodgkin's lymphoma (NHL) cases and 119,450 noncancer controls from 24 states for the period 1984-1989 were used to generate hypotheses regarding occupational associations. Cases were frequency matched by age, race, and gender with five controls per case. Odds ratios were calculated for 231 industries and 509 occupations. Significant associations were observed for a variety of white-collar professionals (i.e., real estate agents, secretaries, bookkeepers, teachers, postal employees, business agents, engineers, chemists, and medical professionals) and blue-collar occupations (i.e., firefighters, farm managers, aircraft mechanics, electronic repairers, mining machine operators, and crane and tower operators). © 1995 Wiley-Liss, Inc.     

Pulsed ultrasound Doppler velocimetry in the assessment of microvascular hemodynamics

Pulsed ultrasonic Doppler velocimetry (20 MHz) (PUDVM) has evolved considerably in the last 10 years. Engineering development has resulted in a computer-controlled vessel-scanning instrument whose backscattered frequency shift spectra are analyzed using fast Fourier transforms (FFT). Benchtop and theoretic studies indicate accurate (error less than 5%) velocity and volumetric flow rate measurements in vessels with a lumen diameter as small as 1.2 mm. Clinical application of the PUDVM has provided transcutaneous measurements of blood flow variables in normal human digital arteries. Experimental application to arteries 1.0-1.5 mm has provided information on the hemodynamic effects of topical vasodilators, standard microarteriorrhaphy, variations in microvascular technique, interpositional grafts, and early wound repair. With improving computer capabilities and technical modifications, the PUDVM will be an increasingly important tool in clinical and experimental microsurgery.     

von Willebrand factor as a marker of endothelial cell activation following BMT.

Endothelial cell activation may play a role in thrombotic complications of BMT such as hepatic veno-occlusive disease (VOD), right atrial line thrombosis and microangiopathic haemolysis. To assess this, von Willebrand factor antigen (vWF:ag) was measured in 72 patients (25 allografts, 46 autografts and one syngeneic) during the first 6 weeks post-transplant. There was a significant rise in vWF:ag in both allografts and autografts but a greater increase was seen in the allografts. The changes in vWF:ag did not correlate with changes in C reactive protein showing that this was not merely an acute phase response. vWF multimers were normal in a subgroup of uncomplicated transplants showing that there was no large scale endothelial cell disruption. Patients with VOD did not have changes in vWF:ag that were consistently different from uncomplicated controls. Three of four patients who developed line thrombosis had higher levels of vWF:ag compared with control groups; multimeric structure of the vWF was again normal. These results show that there is endothelial cell activation post-BMT and that this is greater in allografts compared with autografts, thus suggesting a possible mechanism for the higher incidence of VOD in this group. There were no useful predictive markers of VOD or thrombosis in individual patients.     

13-cis-retinoic acid (NSC 122758) in the treatment of children with metastatic neuroblastoma unresponsive to conventional chemotherapy: Report from the childrens cancer study group

The Childrens Cancer Study Group evaluated daily oral 13-cis-retinoic acid to determine its therapeutic efficacy in 28 children with advanced neuroblastoma refractory to conventional therapy. Cheilitis and fissured lips were the most common side effects; however, fewer than 50% of the patients experienced any toxicity. Two of twenty-two evaluable children demonstrated positive response to therapy. In one case, a child received the drug for 11 months. Seventeen patients demonstrated progressive disease within 28 days of the start of treatment. Three other patients with stable disease, or removed from study at day 28, were considered nonresponsive. Our data demonstrate that, when given as a single daily oral dose of 100 mg/m², 13-cis-retinoic acid does not have significant activity in children with advanced neuroblastoma. © 1992 Wiley-Liss, Inc.     

Recovery from depression after electroconvulsive therapy is accompanied by evidence of increased tetrahydrobiopterin-dependent hydroxylation

Serum phenylalanine and tyrosine levels were measured in 26 patients with severe depression before and after receiving electroconvulsive therapy. The phenylalanine:tyrosine [P:T] ratio declined significantly for those responding to treatment but not for nonresponders. These findings are discussed in relation to tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, dopamine and serotonin and the hydroxylation of phenylalanine to tyrosine.