Solid-state REDOR NMR distance measurements at the ligand site of a bacterial chemotaxis membrane receptor

The Escherichia coli serine receptor senses serine levels in the environment and transmits this information across the bacterial inner membrane to modulate a protein phosphorylation cascade which controls swimming behavior. Solid-state nuclear magnetic resonance (NMR) has been used to characterize specific structural features of the ligand binding site interactions in the intact, membrane-bound Ser receptor. Rotational-echo double-resonance (REDOR) experiments on [15N]Ser bound to a [1-13C]Phe-receptor preparation are used to measure distances between the ligand amino group and the carbonyls of two phenylalanine residues in the ligand binding pocket. The results indicate two 4.0 +/- 0.2 A distances, in excellent agreement with the X-ray crystal structure of a soluble fragment of the homologous aspartate receptor [Milburn et al. (1991) Science 254, 1342-1347]. These results confirm the similarity of the binding sites of the Asp and Ser receptors, and demonstrate the feasibility of using solid-state NMR measurements to obtain specific structural information on the 120 kDa intact receptor for probing transmembrane signaling mechanisms.     

Microalbuminuria: a marker to increased renal and cardiovascular risk in diabetes mellitus

The presence of persistent microalbuminuria in IDDM is strongly predictive of the future development of end stage renal failure and of cardiovascular disease to a lesser extent. Screening for microalbuminuria is an essential component of modern diabetes practice, as effective antihypertensive therapy, and particularly, the use of angiotensin converting enzyme inhibitors is of proven benefit in retarding progression of renal disease. Cost benefit analysis justifies the expense of microalbuminuria screening programmes and early intervention. It has been estimated that the use of angiotensin converting enzyme inhibitors in microalbuminuric IDDM will save 5200 Pounds-11,000 Pounds per year of life saved. Angiotensin converting enzyme inhibitors are not free of side-effects, and it is therefore essential, given the intrinsic variability of the albumin excretion rate, and the regression to normoalbuminuria of a significant proportion of patients, to confirm the diagnosis of microalbuminuria by repeated measurements prior to the commencement of treatment. The value of intensive glycaemic control is unproven, and further prospective studies are required. There are no proven therapies for the prevention of macrovascular disease in IDDM, although the value of cessation of smoking and aggressive blood pressure control are undoubted in the non-diabetic population. Controversy persists about the value of lipid lowering therapy, especially in young patients, although even in this group there is an increased risk of cardiovascular disease. Microalbuminuria is the strongest known predictor of cardiovascular disease in NIDDM; in contrast to the situation in the non-diabetic population, active lipid lowering therapy is not of proven cardiac benefit, but intervention seems justifiable when taken in the context of the very high prevalence of cardiovascular disease. Microalbuminuria is also predictive of end stage renal disease in NIDDM. Although intervention with angiotensin converting enzyme inhibitors has not been proven to prevent end stage renal disease, stabilisation of albumin excretion rate and creatinine clearance have been demonstrated in normotensive NIDDM, and it seems likely that longer term follow-up studies will confirm the benefit of angiotensin converting enzyme inhibitors in the prevention of end-stage renal disease. The observed predictive power of microalbuminuria as regards both cardiac and renal risk in NIDDM when considered in conjunction with the preliminary results of the benefits of angiotensin converting enzyme inhibition lend further support to the employment of microalbuminuria screening in NIDDM.     

Antibiotics: why they fail in patients who are critically ill

Most of the failures of antimicrobial therapy can be related to advanced infections in patients with serious comorbid processes or altered immunity. However, some of the failures are related to the type of antimicrobial therapy used, the length of therapy, the pharmacokinetic or pharmacodynamic properties of the antimicrobial agent, the development of antimicrobial resistance, microbial factors that influence antimicrobial efficacy, and the site and type of infection. This report will review the common mechanisms by which antimicrobials fail.     

Fully Bayesian estimation of Gibbs hyperparameters for emission computed tomography data

In recent years, many investigators have proposed Gibbs prior models to regularize images reconstructed from emission computed tomography data. Unfortunately, hyperparameters used to specify Gibbs priors can greatly influence the degree of regularity imposed by such priors and, as a result, numerous procedures have been proposed to estimate hyperparameter values from observed image data. Many of these procedures attempt to maximize the joint posterior distribution on the image scene. To implement these methods, approximations to the joint posterior densities are required, because the dependence of the Gibbs partition function on the hyperparameter values is unknown. In this paper, we use recent results in Markov chain Monte Carlo (MCMC) sampling to estimate the relative values of Gibbs partition functions and using these values, sample from joint posterior distributions on image scenes. This allows for a fully Bayesian procedure which does not fix the hyperparameters at some estimated or specified value, but enables uncertainty about these values to be propagated through to the estimated intensities. We utilize realizations from the posterior distribution for determining credible regions for the intensity of the emission source. We consider two different Markov random field (MRF) models-the power model and a line-site model. As applications we estimate the posterior distribution of source intensities from computer simulated data as well as data collected from a physical single photon emission computed tomography (SPECT) phantom.     

Hormonal receptors in mammary carcinoma: comparison between quantitative and qualitative methods

Alternatives to the traditional hormone receptor dosages for prognostic evaluation and clinical approach to breast cancer have been proposed for immunohistochemical determinations. For correlation purposes, such procedures were compared in 37 patients presenting 5 to 15 years of survival. Considering 30 fm/mg as the positivity index, the disagreement between both methods reached 35.1% with estrogen and 48.5% with progesterone receptors. When the positiveness level was changed to 20 fm/mg, the discrepancies were reduced to 32% with ER and increased to 57% with PgR. This study leads us to not recommend the immunohistochemical method applied to paraffin sections as an alternative procedure to the dextran-charcoal dosage for prognosis and therapeutic management of mammary carcinoma.     

Microwave Drilling of Ceramic Thermal-Barrier Coatings

The microwave drill is a novel process for creating shaped holes in nonconductive materials. Its inherent material selectivity makes the microwave drill ideally suited for the controlled removal of ceramic coatings from underlying metallic substrates. In this paper, it is shown that the microwave drill process can drill through ceramic thermal barrier coatings (TBCs) to uncover an array of simulated cooling holes. The concept, apparatus, and procedure for successful drilling are described, and the potential for use in the production of advanced gas turbine components is discussed.     

The mini-micro-epididymal sperm aspiration for sperm retrieval: a study of urological outcomes

Susceptible adults (n = 105) were enrolled into a randomized double-blind study of rimantadine treatment of experimental influenza A infection. Subjects were cloistered for 8 days and challenged with a rimantadine-sensitive strain of influenza A H1N1 virus at the end of the first day. Forty-eight hours after challenge and for 8 days, 54 subjects received placebo and 51 received rimantadine (100 mg orally, twice a day). Symptoms, signs, and pathophysiologies were monitored. Nine subjects were not infected. Seventeen subjects (38%) in the rimantadine and 26 (53%) in the placebo group became ill. A beneficial effect of rimantadine was documented for virus shedding, symptom load, and sinus pain. Rimantadine had no effect on nasal patency, mucociliary clearance, nasal signs, or on symptoms and signs of otologic complications. These results do not support a preventive effect of rimantadine on the development of otologic manifestations of influenza A infection in adults.     

Embolization of a ruptured aneurysm in classic polyarteritis nodosa presenting as perirenal hematoma

A 26-year-old man was admitted with abdominal pain, anemia, and hypertension. Ultrasonography and computed tomography revealed a perirenal hematoma. Soon after admission, the patient went into shock, and emergency angiography was performed. Two active bleeding sites were found in the left kidney and were successfully embolized. Also, multiple aneurysms, consistent with the diagnosis of classic polyarteritis nodosa, were seen. After treatment was initiated, the patient recovered fully. When a spontaneous perirenal hematoma is a presenting symptom of classic polyarteritis nodosa, a delay in making the right diagnosis is likely to occur. Angiography not only may provide a quick diagnosis, but it can also be used to perform therapeutic embolization. In patients with classic polyarteritis nodosa and hemorrhage from a ruptured aneurysm, angiography may be a therapeutic alternative to surgery.