Evidence of participation of McrB(S) in McrBC restriction in Escherichia coli K-12

The McrBC restriction system has the ability to restrict DNA containing 5-hydroxymethylcytosine, N4-methylcytosine, and 5-methylcytosine at specific sequences. The mcrB gene produces two gene products. The complete mcrB open reading frame produces a 51-kDa protein (McrB(L)) and a 33-kDa protein (McrB(S)). The smaller McrB polypeptide is produced from an in-frame, internal translational start site in the mcrB gene. The McrB(S) sequence is identical to that of McrB(L) except that it lacks 161 amino acids present at the N-terminal end of the latter protein. It has been suggested that McrB(L) is the DNA binding restriction subunit. The function of McrB(S) is unknown, although there has been speculation that it plays some role in the modulation of McrBC restriction. Studies of the function of McrB(S) have been challenging since it is produced in frame with McrB(L). In this study, we tested the effects of underproduction (via antisense RNA) and overproduction (via gene dosage) of mcrBC gene products on restriction levels of the mcrBC+ strain JM107. Among the parameters monitored was the induction of SOS responses, which indicate of DNA damage. Evidence from this study suggests that McrB(S) is necessary for stabilization of the McrBC restriction complex in vivo.     

Status epilepticus in children and adults

Status epilepticus (SE) in children and adults is one of the most common neurology problems confronting the intensivist. Recognition of SE is usually straightforward, but may be complicated by the effects of other diseases or therapies. Emergent treatment is necessary to prevent further brain damage. This article reviews protocols for standard treatments of SE patients and includes recommendations for the management of refractory SE.     

Thrombocytopenia following liver transplantation is associated with platelet consumption and thrombin generation

PSA-based screening substantially increases the prostate cancer detection rate and the percentage of organ-confined tumors. It appears that there is some benefit from screening for prostate cancer because of the increased amount of potentially curable disease discovered and the fact that 96% of the pathologically staged tumors detected have histologic features associated with aggressive cancer. Additional evidence that nearly all tumors detected on the basis of initial PSA screening are apt to be clinically significant may be derived from the information that PSA-based screening decreases the incidence of incidental A1 grade III and A2 tumors but does not increase the detection of clinically insignificant A1 grade I and II tumors. At this time, PSA represents the most effective and valuable tool to detect early prostate cancer; therefore, PSA should be used to improve early diagnosis of prostate cancer. Some advances have been made with the introduction of age-specific reference ranges and the ability to measure free to total PSA ratios. The data presented support the clinical usefulness of age-specific reference ranges for serum PSA. Calculation of the free to total PSA ratio is valuable in deciding which screening volunteers require further evaluation, increases the specificity of PSA screening, and as demonstrated may be useful in deciding which patients with isolated PIN should undergo repeat biopsies. Based on these facts, PSA truly can be described as the most important and useful marker for adenocarcinoma of the prostate. Based on these encouraging results and the obligingness of the social insurances, we will be able to continue PSA screening for early detection of prostate cancer for all concerned Tyrolean men in the future.     

Human Mycobacterium bovis infection in the south-west of Ireland 1983-1992: a comparison with M. tuberculosis

Epidemiological and bacteriological aspects of human Mycobacterium bovis disease were investigated in south-west Ireland (counties Cork & Kerry, population 536,000) over the years 1983-92 inclusive and compared to M. tuberculosis. Results showed a small, stable incidence of culture positive M. bovis human disease, mean annual incidence 0.56 per 100,000 population compared to a higher but declining incidence of culture positive M. tuberculosis (15.3 per 100,000 in 1983, 9.0 per 100,000 in 1992). Male patients were the majority, 63.4 per cent of M. bovis; 62.4% of M. tuberculosis (p = 0.03). Fifty three per cent of M. bovis cases (n = 30) were pulmonary, compared to 85% of M. tuberculosis (n = 626; p = 0.0001). M. bovis patients were older (p = 0.02), mean age 58.4 years (SD 18.9) compared to 48.5 (SD 22.2). The mycobacterial smear positive rate was similar in both groups taken as a whole. No rural-urban difference in incidence was found in either disease, suggesting in the case of M. bovis initial infection in childhood via contaminated milk in the pre-pasteurisation era.     

Relation between chemosensitivity and the ventilatory response to exercise in chronic heart failure

OBJECTIVES: This study sought to establish the chemosensitivity of patients with chronic heart failure. BACKGROUND: The ventilatory response to exercise is often increased in patients with chronic heart failure, as characterized by the steeper regression slope relating minute ventilation to carbon dioxide output. We hypothesized that the sensitivity of chemoreceptors may be reset and may in part mediate the exercise hyperpnea seen in this condition. METHODS: Hypoxic and peripheral hypercapnic chemosensitivity were studied in 38 patients with chronic heart failure (35 men, 3 women; mean [+/-SE] age 60.2 +/- 1.3 years; radionuclide left ventricular ejection fraction 25.7 +/- 2.3%) and 15 healthy control subjects (11 men, 4 women; mean age 54.9 +/- 3.0 years) using transient inhalations of pure nitrogen and single breaths of 13% carbon dioxide, respectively. The change in chemosensitivity during mild exercise (25 W) was assessed in the first 15 patients and all control subjects. Central hypercapnic chemosensitivity was also characterized in 25 patients and 10 control subjects by the rebreathing of 7% carbon dioxide in 93% oxygen. Cardiopulmonary exercise testing was performed in all subjects. RESULTS: Maximal oxygen consumption was 16.6 +/- 0.9 versus 29.7 +/- 2.2 mol/kg per min (p < 0.0001), and the ventilation-carbon dioxide output regression slope was 37.2 +/- 1.5 versus 26.5 +/- 1.4 (p < 0.0001) in patients and control subjects, respectively. Hypoxic and central hypercapnic chemosensitivity were enhanced in patients (0.707 +/- 0.076 vs. 0.293 +/- 0.056 liters/min per % arterial oxygen saturation [SaO2], p = 0.0001 and 3.15 +/- 0.41 vs. 2.02 +/- 0.25 liters/min per mm Hg, p = 0.025, respectively) and correlated significantly with the ventilatory response to exercise. Hypoxic chemosensitivity was augmented during exercise in patients and in control subjects but remained higher in the former (1.530 +/- 0.27 vs. 0.685 +/- 0.12 liters/min per %SaO2, p = 0.01). The peripheral hypercapnic chemosensitivity of patients at rest and during exercise was similar to that in control subjects, consistent with its lesser contribution to overall carbon dioxide chemosensitivity. CONCLUSIONS: Enhanced hypoxic and central hypercapnic chemosensitivity may play a role in mediating the increased ventilatory response to exercise in chronic heart failure.     

Identification of race and sex from palate dimensions

Measurements of the width and depth of the palate were used to predict the race (American black or white) or sex or both of an individual. The sample consisted of 332 living subjects with permanent dentitions, and measurements were made between cusp tips, so palate size includes bony and dental components. Blacks, with a more square palate, were distinguished from whites primarily by greater interpremolar widths and P1-to-M2 depths. Simultaneous prediction of race and sex had a correct classification of 48%, which is about twice that expected from chance. Pooling the two sex increases correct classification of race to 83%. Formulas also are provided for each variable separately to accommodate fragmentary remains. Resilience of palatal structures to traumatic and natural forces makes this method practical in several forensic situations.     

Flauoprotein structure and mechanism 2. Monoamine oxidases: old friends hold many surprises

The two forms of monoamine oxidase (MAO), A and B, continue to be of major interest to biochemists, pharmacologists, neurologists, and gerontologists. Despite intensive study for more than half a century, unexpected and unique properties of these enzymes continue to come to light. Recent studies have centered on their kinetic mechanism, their unique predilection for substrates related to the neurotoxic tertiary amine MPTP, and their putative role in aging and in the etiology of neurodegenerative diseases. New and potent inhibitors of MAO A and MAO B continue to be developed because of their potential use in clinical medicine. Some are effective in the picomolar range but MAO B from different mammalian species shows remarkable differences in sensitivity to these agents.