Comparison of Track XI fluorometric immunoassay with Bio-EnzaBead enzyme-linked immunosorbent assay for detection of serum antibody to mouse hepatitis virus.

The Track XI system (Microbiological Associates, Bethesda, Md.) was compared with the Bio-EnzaBead assay (Organon Teknika, Durham, N.C.) for the detection of antibody to mouse hepatitis virus (MHV). Strain A/J mice were inoculated intranasally with MHV type 3. Sera were collected at 1, 2, 4, and 9 weeks postinoculation and tested. Individual serum samples were retested twice by each method. The results suggested that the Track XI system was more sensitive and reliable than the Bio-EnzaBead assay in detecting antibody to MHV type 3 in individual serum samples from A/J mice.     

Analysis of Host Cells Associated with the Spv-Mediated Increased Intracellular Growth Rate of Salmonella typhimurium in Mice

The 90-kb virulence plasmid of Salmonella typhimurium encodes five spv genes which increase the growth rate of the bacteria within host cells within the first week of systemic infection of mice (P. A. Gulig and T. J. Doyle, Infect. Immun. 61:504–511, 1993). The presently described study was aimed at identifying the host cells associated with Spv-mediated virulence by manipulating the mouse host and the salmonellae. To test the effects of T cells and B cells on the Spv phenotype, salmonellae were orally inoculated into nude and SCID BALB/c mice. Relative to normal BALB/c mice, nude and SCID BALB/c mice were unaffected for splenic infection with either the Spv⁺ or Spv⁻ S. typhimurium strains at 5 days postinoculation. When mice were pretreated with cyclophosphamide to induce granulocytopenia, there was a variable increase in total salmonella infection, but the relative splenic CFU of Spv⁺ versus Spv⁻ S. typhimurium was not changed after oral inoculation. In contrast, depletion of macrophages from mice by treatment with cyclophosphamide plus liposomes containing dichloromethylene diphosphate resulted in equivalent virulence of Spv⁺ and Spv⁻ salmonellae. To examine if the spv genes affected the growth of salmonellae in nonphagocytic cells, an invA::aphT mutation was transduced into Spv⁺ and Spv⁻ S. typhimurium strains. InvA⁻ Spv⁺ salmonellae were not significantly affected for splenic infection after subcutaneous inoculation compared with the wild-type strain, and InvA⁻ Spv⁻ salmonellae were only slightly attenuated relative to InvA⁺ Spv⁻ salmonellae. Invasion-defective salmonellae still exhibited the Spv phenotype. Therefore, infection of nonphagocytes is not involved with the Spv virulence function. Taken together, these data demonstrate that macrophages are essential for suppressing the infection by Spv⁻ S. typhimurium, by serving as the primary host cell for Spv-mediated intracellular replication and possibly by inhibiting the replication of salmonellae within other macrophages.     

Increased seminal plasma lead levels adversely affect the fertility potential of sperm in IVF

BACKGROUND: Lead remains in high levels in the environment and is known to reduce fertility in animal models, but a direct link between lead exposures and human infertility has not yet been established. METHODS: In a prospective, double-blind study of the metal ion levels and sperm function, semen was obtained from partners of 140 consecutive women undergoing their first IVF cycle. Lead in seminal plasma was determined by atomic absorption spectroscopy. Motile sperm populations were assessed for surface receptors for mannose binding, and the ability to undergo premature ('spontaneous'), and free mannose-induced acrosome reactions. Fertile donor (n = 9) sperm were exposed to exogenous lead during capacitating incubations and then assessed for mannose receptor expression and acrosome loss. RESULTS: Lead levels were negatively correlated with IVF rates. Lead levels were negatively correlated to two of the three sperm function biomarkers (mannose receptors, mannose-induced acrosome reactions). Lead levels positively correlated with the spontaneous acrosome reaction. These findings were mimicked by in-vitro exposure of fertile donor sperm to lead. CONCLUSIONS: Multiple sperm parameters are affected as lead levels rise. Increased lead levels may contribute to the production of unexplained male infertility.     

Transcranial direct current stimulation of the primary motor cortex affects cortical drive to human musculature as assessed by intermuscular coherence

Intermuscular coherence analysis can be used to assess the common drive to muscles. Coherence in the β-frequency band (15–35 Hz) is thought to arise from common cortical sources. Intermuscular coherence analysis is a potentially attractive tool for the investigation of motor cortical excitability changes because it is non-invasive and can be done relatively quickly. We carried out this study to test the hypothesis that intermuscular coherence analysis was able to detect cortical excitability changes in healthy subjects following transcranial direct current stimulation (tDCS). tDCS has been shown to increase (anodal stimulation) or decrease (cathodal stimulation) the size of the muscle potential evoked by TMS. We found that anodal tDCS caused an increase in motor evoked potential (MEP) size that was paralleled by an increase in β-band intermuscular coherence. Similarly, the reduction in MEP size produced by cathodal tDCS was paralleled by a reduction in β-band intermuscular coherence, while sham stimulation did not result in any change in either MEP amplitude or β-band intermuscular coherence. The similar pattern of change observed for MEP and intermuscular coherence may indicate similar mechanisms of action, although this cannot be assumed without further investigation. These changes do suggest that at least some of the action of tDCS is on cortical networks, and that combined tDCS and intermuscular coherence analysis may be useful in the diagnosis of pathologies affecting motor cortical excitability.     

Modeling a medical environment: an ontology for integrated medical informatics design

Modern medical environments have seen an increase in technological complexity and pressures of handling more patients with fewer resources, resulting in higher demands on medical practitioners. Medical informatics designers will have to focus on the problem of organizing medical information more effectively to enable practitioners to cope with these challenges. This article addresses this research problem for the particular area of medical problem solving in patient care. First, we describe a traditional modeling approach for medical reasoning used as a basis for developing some decision support systems. We argue these models may be faithful to what is known about biomedical knowledge, but they have limitations for human problem solving, especially in unanticipated situations. Second, we present an ontological framework, known as the abstraction hierarchy (Rasmussen, IEEE Trans. Man. Cybernetics 15 (1985) 234-243), for integrating patient representations that are faithful to existing biomedical knowledge and that are consistent with what is known about human problem solving. Through an example of a critical event in the operating room, we reveal how this framework can support medical problem solving in unanticipated situations. Third, we show how to use these representations as a frame of reference for mapping medical roles, responsibilities, sensors, and controls in an operating room context. Finally, we provide some insight for medical informatics designers in using this framework to design novel training programs and human-computer displays.     

Role of CD 11/CD 18 in neutrophil emigration during acute and recurrent Pseudomonas aeruginosa-induced pneumonia in rabbits.

This study examined CD11/CD18-mediated adhesion in neutrophil emigration during acute and recurrent Pseudomonas aeruginosa-induced pneumonia. Neutrophil emigration during acute pneumonia was studied in anti-CD18 antibody or murine-IgG-pretreated rabbits 4 hours after intrabronchial instillation of P. aeruginosa. To examine emigration in recurrent pneumonias, rabbits given P. aeruginosa on day 0 received anti-CD18 antibody or IgG on day 7. A second instillate was placed either at the initial site or in a separate lobe, and emigration into alveolar spaces was quantitated morphometrically after 4 hours. The results show that CD11/CD18 was required for neutrophil emigration in acute pneumonias and in recurrent pneumonias that occurred at a site distant from the initial infection. However, when the recurrent pneumonia occurred in the previously inflamed site, CD11/CD18 was not required. When the same number of organisms were instilled on days 0 and 7, emigration was reduced to 15 to 20 percent of the number that migrated initially and only CD18-independent adhesion pathways were used. Increasing the concentration of organisms threefold increased emigration through both CD18-dependent and CD18-independent pathways. These data indicate that P. aeruginosa induces CD11/CD18-dependent emigration during acute pneumonia and recurrent pneumonia at previously uninflamed sites. However, adhesion pathways are altered in regions of chronic inflammation, and a greater proportion of neutrophil emigration occurs through CD11/CD18-independent pathways.     

Lectins in diagnostic microbiology

Current literature suggests that lectins are becoming valuable reagents for the laboratory identification of infectious agents. The identification of bacteria, fungi, or protozoa may be confirmed if they bind to or agglutinate with certain lectins. Assay kits utilizing specific lectin agglutination reactions, coupled with conventional enzyme determinations, have been proposed for several bacteria. Factors such as specificity, stability, assay rapidity, and costs combine to make lectins attractive diagnostic reagents. It is likely that the use of lectins in diagnostic microbiology will continue to grow.     

Changes in the nuclei of astrocytes following portacaval shunting and portacaval transposition in the rat.

Structural abnormalities are found in the astrocytes of the dentate nuclei of animals after portacaval shunting (PCS). These changes are also found in man in association with portal-systemic encephalopathy. To investigate the relationship between portal-systemic shunting and hepatocellular dysfunction in the pathogenesis of these changes, PCS and protacaval transposition (PCT) were performed in rats. PCT diverts portal blood into the systemic circulation, but retains normal total hepatic blood flow by perfusion with systemic venous blood. Liver function and mass are better preserved than after PCS. Abnormal glial cells were found in 4.03% of animals following sham operation, 13.45% following PCT, and 19.09% following PCS. Both experimental groups differed significantly from control animals, and the number of abnormal cells was significantly higher after PCS than after PCT. These findings are in keeping with the hypothesis that hepatocellular dysfunction plays an important role in addition to portal-systemic shunting in the aetiology of the structural changes in the brain associated with hepatic encephalopathy.