Comparison of the resistance of C57BL/6 and C3H/He mice to infection with Mycobacterium paratuberculosis

Susceptibility of C57BL/6 (Bcgs) and C3H/HeN (Bcgr) mice to an intraperitoneal infection with Mycobacterium paratuberculosis strain 19698 was compared (by histopathology and the number of mycobacteria isolated from the spleen). Mycobacterial counts from the spleen of Bcgr mice progressively decreased over the course of infection but remained unchanged in Bcgs mice. Granulomatous lesions and acid-fast bacteria were consistently present in the liver and lymph nodes of Bcgs mice, whereas lesions were transient or absent in Bcgr mice. These results indicate that Bcgr mice are inherently resistant to M. paratuberculosis, whereas Bcgs mice are inherently susceptible. These differences may prove useful in elucidating the mechanisms of resistance and susceptibility to paratuberculosis and other mycobacterial infections.     

Physical fitness, physical activity, and functional limitation in adults aged 40 and older

PURPOSE: A cohort of middle-aged and older men and women were followed for an average of 5.5 yr to examine the association between physical fitness, physical activity, and the prevalence of functional limitation. METHODS: The participants received medical assessments between 1980 and 1988 and responded to a mail-back survey regarding functional status in 1990. RESULTS: Among 3495 men and 1175 women over 40 yr of age at baseline, 350 (7.5%) reported at least one functional limitation in daily or household activities at follow-up. The prevalence of functional limitation was higher among women than men. Physically fit and physically active participants reported less functional limitation than unfit or sedentary participants. After controlling for age and other risk factors, the prevalence of functional limitation was lower for both moderately fit (odds ratio = 0.4, 95% CI = 0.2-0.6) and high fit men (odds ratio = 0.3, 95% CI = 0.2-0.4), compared with low fit men. Corresponding figures for women were 0.5 (0.3-0.7) and 0.3 (0.2-0.5) for moderately fit and high fit women. The association between physical activity and functional limitation was similar to the data for physical fitness. CONCLUSIONS: These data support a protective effect of physical fitness and physical activity on functional limitation among older adults and extend this protective effect to middle-aged men and women.     

Disposition and elimination of meropenem in cerebrospinal fluid of hydrocephalic patients with external ventriculostomy

The broad antibacterial spectrum and the low incidence of seizures in meropenem-treated patients qualifies meropenem for therapy of bacterial meningitis. The present study evaluates concentrations in ventricular cerebrospinal fluid (CSF) in the absence of pronounced meningeal inflammation. Patients with occlusive hydrocephalus caused by cerebrovascular diseases, who had undergone external ventriculostomy (n = 10, age range 48 to 75 years), received 2 g of meropenem intravenously over 30 min. Serum and CSF were drawn repeatedly and analyzed by liquid chromatography-mass spectroscopy. Pharmacokinetics were determined by noncompartmental analysis. Maximum concentrations in serum were 84.7 +/- 23.7 microg/ml. A CSF maximum (CmaxCSF) of 0.63 +/- 0.50 microg/ml (mean +/- standard deviation) was observed 4.1 +/- 2.6 h after the end of the infusion. CmaxCSF and the area under the curve for CSF (AUCCSF) depended on the AUC for serum (AUCS), the CSF-to-serum albumin ratio, and the CSF leukocyte count. Elimination from CSF was considerably slower than from serum (half-life at beta phase [t1/2beta] of 7.36 +/- 2.89 h in CSF versus t1/2beta of 1.69 +/- 0.60 h in serum). The AUCCSF/AUCS ratio for meropenem, as a measure of overall CSF penetration, was 0.047 +/- 0.022. The AUCCSF/AUCS ratio for meropenem was similar to that for other beta-lactam antibiotics with a low binding to serum proteins. The concentration maxima of meropenem in ventricular CSF observed in this study are high enough to kill fully susceptible pathogens. They may not be sufficient to kill bacteria with a reduced sensitivity to carbapenems, although clinical success has been reported for patients with meningitis caused by penicillin-resistant pneumococci and Pseudomonas aeruginosa.     

Polarity as a criterion in protein design

Hypothetical proteins can be tested computationally by determiningwhether or not the designed sequence-structure pair has thecharacteristics of a typical globular protein. We have developedsuch a test by deriving quantities with approximately constantvalue for all globular proteins, based on empirical analysisof the exposed and buried surfaces of 128 structurally knownproteins. The characteristic quantities that best appear tosegregate badly designed or deliberately misfolded proteinsfrom their properly folded natural relatives are the polar fractionof side chains on the protein surface and, independently, inthe protein interior. Three of the seven hypothetical structurestested here can be rejected as having too many polar side-chaingroups in the interior or too few on the protein surface. Inaddition, a recently designed nutritional protein is identifiedas being very much unlike globular proteins. These database-derivedcharacteristic quantities are useful in screening designed proteinsprior to experiment and may be useful in screening experimentallydetermined (X-ray, NMR) protein structures for possible errors.     

Generation, Characterization, and Impact of Mesopores in Zeolite Catalysts

Amongst the current developments in the field of hierarchical pore structures, the creation of mesopores in zeolite crystals is the most frequently employed way to combine micropores with mesopores in one material. In this review an overview is presented of the different approaches to generate and characterize mesopores in zeolite crystals and establish their impact on the catalytic action. Mesopores can be created via several routes from which steaming and acid leaching are the most frequently applied. Novel approaches using secondary carbon templates that are removed after synthesis have recently been launched. For the characterization of mesopores, nitrogen physisorption and electron microscopy are commonly used. More recently, it was shown that electron tomography, a form of three-dimensional transmission electron microscopy, is able to reveal the three-dimensional shape, size, and connectivity of the mesopores. The effect of the presence of mesopores for catalysis is demonstrated for several industrially applied processes that make use of zeolite catalysts: the cracking of heavy oil fractions over zeolite Y, the production of cumene and hydroisomerization of alkanes over mordenite, and synthesis of fine chemicals over Y, ZSM-5, and Beta. For these processes, the mesopores ensure an optimal accessibility and transport of reactants and products, while the zeolite micropores induce the preferred shape-selective properties.     

The role of heat-shock and chaperone proteins in protein folding: possible molecular mechanisms

Recently some heat-shock proteins have been linked to functionsof ‘chaperoning’ protein folding in vivo. Here currentexperimental evidence is reviewed and possible requirementsfor such an activity are discussed. It is proposed that onemode of chaperone action is to actively unfold misfolded orbadly aggregated proteins to a conformation from whkh they couldrefold spontaneously; that improperly folded proteins are recognizedby excessive stretches of solvent-exposed backbone, rather thanby exposed hydrophobic patches; and that the molecular mechanismfor unfolding is either repeated binding and dissociation (‘plucking’)or translocation of the protein backbone through a binding cleft(‘threading’), allowing the threaded chain to refoldspontaneously. The observed hydrolysis of ATP would providethe energy for active unfolding. These hypotheses can be appliedto both monomeric folding and oligomeric assembly and are sufficientlydetailed to be open to directed experimental verification.     

Gewinnung von Brennstoff für Kraftwerke aus Klärschlamm

Production of a combustible for coal-fired power stations based on sewage sludge . This article describes various means of achieving more extensive mechanical dewatering of sewage sludges. The heat content of the sludge solids can become available for combustion processes. The sludge filter cakes obtained by the “CarboSed” process can be disposed of with minimum energy consumption by fluidized bed combustion or be used after appropriate work-up as a combustible in coal-fired power stations with full exploitation of their heat content for generation of steam and electric current. Partial substitution of primary energy sources such as coal and fuel oil by sludge filter cake is feasible in all cases. The processes thus make a contribution to the saving of energy resources and the disposal of sludge.     

Seroprevalence of antibodies to Bartonella henselae in patients with cat scratch disease and in healthy controls: evaluation and comparison of two commercial serological tests

As the National Library of Medicine expands access to its products and services by making them available on the Internet, more accurate information about current and future access in medical libraries is needed. The National Network Office of the National Library of Medicine conducted a survey of all network member libraries to determine the extent of connectivity and the barriers preventing 100% connectivity. Respondents called a toll-free number and, using interactive voice technology, answered questions concerning Internet access in their library. Seventy-eight percent of the network member libraries responded. Four percent of academic libraries, 27% of hospital libraries, and 10% of "other" libraries reported that they were not connected. Computer cost, lack of in-house expertise, and lack of management support were the highest ranked barriers to connecting. The National Library of Medicine and the Regional Medical Libraries will use information from this survey to develop strategies to help all member libraries achieve full connectivity.