Lupus erythematosus-like features in patients with cutaneous T-cell lymphoma

The purpose of this clinical study was to review experience in the management, and outcome of eclamptic patients at Rajavithi Hospital. Standardized treatment for all cases of eclampsia has consisted of magnesium sulfate intravenously and intramuscularly to control convulsions by means of Chesley and Tepper's regimen, intravenous hydralazine intermittently to lower diastolic blood pressure when it exceeds 110 mmHg, and initiation of delivery as soon as the patient has regained consciousness and is stable. During a ten-year period there were 167,200 deliveries and 90 eclamptic patients, yielding an incidence of eclampsia of 1 in 1,857 deliveries. There were three maternal deaths (3.3%) due to intracerebral hemorrhage. Serious adverse maternal outcomes were more frequent in women whose convulsions occurred before delivery. Excluding postpartum cases, perinatal mortality of fetuses weighing 1,000 g or more was 11.7 per cent. Magnesium sulfate is the drug of choice for treatment of eclamptic convulsions. In most situations, clinical assessment of deep tendon reflexes, respirations, and urine output is adequate to monitor maternal magnesium toxicity without the need to determine actual maternal serum magnesium levels.     

Relationship between interpersonal psychotherapy problem areas with temperament and character: a pilot study

Hematogenous leukocytes infiltrate the CNS after inflammatory stimuli, including infection, mechanical trauma and excitotoxic neuronal necrosis. However,the role of leukocytic inflammation in promoting or hindering tissue repair is poorly understood. Identification of signals that lead to leukocyte recruitment and activation is essential for the designing of interventions that modulate inflammation, thus improving neurological outcome. Chemokines are small pleiotropic chemoattractant cytokines whose target specificity suggests an important role in determining the cellular composition of inflammatory infiltrates. Chemokine expression profiles in the CNS during autoimmune and post-traumatic inflammation correlate well with the composition of leukocyte infiltrates, and expression studies in systems such as transgenic mice, suggest that chemokines have potent functional attributes in CNS physiology. We propose that selective chemokine expression by CNS cells is crucial for post-traumatic leukocyte accumulation.     

The catalytic site of cytochrome P4504A11 (CYP4A11) and its L131F mutant

CYP4A11, the principal known human fatty acid omega-hydroxylase, has been expressed as a polyhistidine-tagged protein and purified to homogeneity. Based on an alignment with P450BM-3, the CYP4A11 L131F mutant has been constructed and similarly expressed. The two proteins are spectroscopically indistinguishable, but wild-type CYP4A11 primarily catalyzes omega-hydroxylation, and the L131F mutant only omega-1 hydroxylation, of lauric acid. The L131F mutant is highly uncoupled in that it slowly (omega-1)-hydroxylates lauric acid yet consumes NADPH at approximately the same rate as the wild-type enzyme. Wild-type CYP4A11 is inactivated by 1-aminobenzotriazole under turnover conditions but the L131F mutant is not. This observation, in conjunction with the binding affinities of substituted imidazoles for the two proteins, indicates that the L131F mutation decreases access of exogenous substrates to the heme site. Leu-131 thus plays a key role in controlling the regioselectivity of substrate hydroxylation and the extent of coupled versus uncoupled enzyme turnover. A further important finding is that the substituted imidazoles bind more weakly to CYP4A11 and its L131F mutant when these proteins are reduced by NADPH-cytochrome P450 reductase than by dithionite. This finding suggests that the ferric enzyme undergoes a conformational change that depends on both reduction of the iron and the presence of cytochrome P450 reductase and NADPH.     

The structure of an insect parvovirus (Galleria mellonella densovirus) at 3.7 A resolution

BACKGROUND: Parvoviruses infect vertebrates, insects and crustaceans. Many arthropod parvoviruses (densoviruses) are highly pathogenic and kill approximately 90% of the host larvae within days, making them potentially effective as selective pesticides. Improved understanding of densoviral structure and function is therefore desirable. There are four different initiation sites for translation of the densovirus capsid protein mRNA, giving rise to the viral proteins VP1 to VP4. Sixty copies of the common, C-terminal domain make up the ordered part of the icosahedral capsid. RESULTS: The Galleria mellonella densovirus (GMDNV) capsid protein consists of a core beta-barrel motif, similar to that found in many other viral capsid proteins. The structure most closely resembles that of the vertebrate parvoviruses, but it has diverged beyond recognition in many of the long loop regions that constitute the surface features and intersubunit contacts. The N termini of twofold-related subunits have swapped their positions relative to those of the vertebrate parvoviruses. Unlike in the vertebrate parvoviruses, in GmDNV there is no continuous electron density in the channels running along the fivefold axes of the virus. Electron density corresponding to some of the single-stranded DNA genome is visible in the crystal structure, but it is not as well defined as in the vertebrate parvoviruses. CONCLUSIONS: The sequence of the glycine-rich motif, which occupies each of the channels along the fivefold axes in vertebrate viruses, is conserved between mammalian and insect parvoviruses. This motif may serve to externalize the N-terminal region of the single VP1 subunit per particle. The domain swapping of the N termini between insect and vertebrate parvoviruses may have the effect of increasing capsid stability in GmDNV.     

Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance

BACKGROUND: Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A. PURPOSE: We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. METHODS: A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. RESULTS: No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). CONCLUSIONS: Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. IMPLICATIONS: While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.     

Laparoscopic management of adnexal masses in premenopausal and postmenopausal women

OBJECTIVE: Caffeine is by far the most commonly consumed psychoactive substance. The use and abuse of most other licit and illicit psychoactive drugs have been shown to be substantially heritable. However, the impact of genetic factors on caffeine consumption, heavy use, intoxication, tolerance, and withdrawal is largely unknown. METHOD: Caffeine consumption, in the form of brewed coffee, instant coffee, tea, and caffeinated soft drinks, as well as caffeine intoxication, tolerance, and withdrawal, were assessed by personal interviews of 1,934 individual twins from female-female pairs ascertained from the population-based Virginia Twin Registry. The sample included both members of 486 monozygotic and 335 dizygotic pairs. Twin resemblance was assessed by probandwise concordance, odds ratios, and tetrachoric correlations. Biometrical model fitting was also performed. RESULTS: The resemblance in twin pairs for total caffeine consumption, heavy caffeine use, caffeine intoxication, caffeine tolerance, and caffeine withdrawal was substantially greater in monozygotic than in dizygotic twin pairs. Model fitting suggested that twin resemblance for these measures could be ascribed solely to genetic factors, with estimated broad heritabilities of between 35% and 77%. CONCLUSIONS: Caffeine is an addictive psychoactive substance. Similar to previous findings with other licit and illicit psychoactive drugs, individual differences in caffeine use, intoxication, tolerance, and withdrawal are substantially influenced by genetic factors.     

Coarctation of the aorta: collateral flow assessment with phase-contrast MR angiography

OBJECTIVE: The purpose of this report is to describe a new use of MR imaging in coarctation of the aorta. The specific question addressed was how well collateral blood flow in intercostal arteries, as determined by phase-contrast MR angiography, correlated with findings during surgery or catheterization in patients with coarctation of the aorta. CONCLUSION: Phase-contrast MR angiography is an excellent technique for detecting the presence or absence of collateral blood flow in the intercostal arteries of patients with coarctation of the aorta. Knowing whether collateral blood flow is present in patients with narrowing of the juxtaductal aorta should help assess the clinical hemodynamic significance of the coarctation.     

Production, purification and characterization of a 50-kDa extracellular metalloprotease from Serratia marcescens

The extracellular metalloprotease (SMP 6.1) produced by a soil isolate of Serratia marcescens NRRL B-23112 was purified and characterized. SMP 6.1 was purified from the culture supernatant by ammonium sulfate precipitation, acetone fractional precipitation, and preparative isoelectric focusing. SMP 6.1 has a molecular mass of approximately 50,900 Da by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE). The following substrates were hydrolyzed: casein, bovine serum albumin, and hide powder. SMP 6.1 has the characteristics of a metalloprotease, a pH optimum of 10.0, and a temperature optimum of 42 degrees C. The isoelectric point of the protease is 6.1. Restoration of proteolytic activity by in-gel renaturation after SDS-PAGE indicates a single polypeptide chain. SMP 6.1 is inhibited by EDTA (9 micrograms/ml) and not inhibited by antipain dihydrochloride (120 micrograms/ml), aprotinin (4 micrograms/ml), bestatin (80 micrograms/ml), chymostatin (50 micrograms/ml), E-64 (20 micrograms/ml), leupeptin (4 micrograms/ml), Pefabloc SC (2000 micrograms/ml), pepstatin (4 micrograms/ml), phosphoramidon (660 micrograms/ml), or phenylmethylsulfonyl fluoride (400 micrograms/ml). SMP 6.1 retains full activity in the presence of SDS (1% w/v), Tween-20 (1% w/v), Triton X-100 (1% w/v), ethanol (5% v/v), and 2-mercaptoethanol (0.5% v/v). The extracellular metalloprotease SMP 6.1 differs from the serratiopeptidase (Sigma) produced by S. marcescens ATCC 27117 in the following characteristics: isoelectric point, peptide mapping and nematolytic properties.