The impact of same-day tests versus traditional overnight testing

Within the last decade, major technologic advances have been made in clinical microbiology that have resulted in the availability of a wide variety of different methods for the rapid reporting of test results. Included among these technologies are rapid methods for producing antimicrobial susceptibility reports that many regard as the most important information generated by the microbiology laboratory. Ideally, the early availability of this important information should favorably affect patient care by enabling the more judicious use of alternative drug therapies that are equally efficacious yet less toxic and less costly to the patient. Clinicians appear to have been reluctant to modify initial empiric therapies, however, despite the availability of the rapid antimicrobial susceptibility report. This article addresses some of the issues responsible for this long-standing problem and discusses and explores various strategies that can be implemented for improving the use and for controlling the cost of antimicrobial agents within the hospital.     

Liver glutathione content and glutathione-dependent enzymes of two species of freshwater fish as bioindicators of chemical pollution

Glutathione content and glutathione-dependent enzymes were measured in the liver of two fish species, gudgeon (Gobio gobio) and roach (Rutilus arcasii), from the river Bernesga (Spain) caught downstream and upstream of the waste site of several chemical industries. Animals from contaminated sites display a reduced glutathione concentration and a tendency to the decrease of glutathione S-transferase activity. Glutathione peroxidase activity was significantly elevated only in the liver of Gobio gobio and glutathione reductase activity in that of Rutilus arcasii. Our data indicate that the glutathione system constitutes a sensitive biochemical indicator of chemical pollution. Relative changes of glutathione and glutathione-dependent enzymes in both fish species suggest a different susceptibility to toxins.     

Epitope specificity of CD44 for monoclonal antibody-dependent facilitation of marrow engraftment in a canine model

Primary graft rejection after marrow transplantation occurs more frequently in patients receiving HLA-haploidentical compared with HLA-identical sibling transplants. Both human and experimental animal data suggest that the cells responsible for this phenomenon are either host natural killer (NK) cells, T cells, or both. To investigate the mechanisms of graft rejection, we have developed a canine model of marrow transplantation, which uses DLA-nonidentical unrelated donors in the absence of postgrafting immunosuppression. In this model most animals rejected their marrow grafts after a preparative regimen of 9.2 Gy total body irradiation (TBI). However, engraftment of DLA-nonidentical marrow can be facilitated when the recipients are pretreated with monoclonal antibody (MoAb) S5, which recognizes CD44. In this report, we extended these observations by first cloning the canine CD44 and, next, mapping the epitope recognized by S5, which was located in a region conserved among human and canine CD44 and was distinct from the hyaluronan binding domain. However, in vitro binding of S5 caused a conformational change in CD44, which allowed increased hyaluronan binding. Then, we reexamined the in vivo model of marrow transplantation and compared results with MoAb S5 to those with two other anti-CD44 MoAbs, IM7 and S3. Only MoAb S5 significantly increased the engraftment rate of DLA-nonidentical unrelated marrow, whereas the two other anti-CD44 MoAbs were ineffective. The enhanced in vivo effect was not related to differences in the MoAbs' avidities, since both S5 and IM7 had equivalent binding to CD44, but most likely related to the specific epitope that S5 recognizes. Thus, this study shows that the effect of the anti-CD44 MoAb S5 in facilitating engraftment is epitope specific and if one is to use an anti-CD44 to facilitate engraftment of marrow in humans, one cannot assume that any anti-CD44 would work.     

A role for herpes simplex virus in the aetiology of chronic fatigue syndrome and related disorders

To evaluate the difference in left ventricular function during exercise after successful aortic valve replacement, left ventricular function was investigated using radionuclide angiography in 12 patients with normal resting left ventricular systolic function. Patients were divided into two groups: Group 1 was comprised of 5 patients after aortic valve replacement for aortic stenosis and group 2 was comprised of 7 patients for aortic insufficiency. Left ventricular ejection fraction increased significantly during exercise in both groups. The increase in systolic arterial pressure to left ventricular end-systolic volume was significantly larger in group 1 than group 2, whereas the increase in left ventricular end-diastolic volume was significantly larger in group 2 than group 1. Thus, increase in left ventricular contractility played an important role in regulating increased left ventricular ejection fraction during exercise in patients with aortic prostheses for aortic stenosis, whereas increase in left ventricular end-diastolic volume played an important role in patients with aortic prostheses for aortic insufficiency.     

The initiation of simian virus 40 DNA replication in vitro

DNA replication is a complicated process that is largely regulated during stages of initiation. The Siman Virus 40 in vitro replication system has served as an excellent model for studies of the initiation of DNA replication, and its regulation, in eukaryotes. Initiation of SV40 replication requires a single viral protein termed T-antigen, all other proteins are supplied by the host. The recent determination of the solution structure of the T-antigen domain that recognizes the SV40 origin has provided significant insights into the initiation process. For example, it has afforded a clearer understanding of origin recognition, T-antigen oligomerization, and DNA unwinding. Furthermore, the Simian virus 40 in vitro replication system has been used to study nascent DNA formation in the vicinity of the viral origin of replication. Among the conclusions drawn from these experiments is that nascent DNA synthesis does not initiate in the core origin in vitro and that Okazaki fragment formation is complex. These and related studies demonstrate that significant progress has been made in understanding the initiation of DNA synthesis at the molecular level.     

Identification and characterization of the murine homologue of CD22, a B lymphocyte-restricted adhesion molecule

The human B lymphocyte-specific Ag, CD22, is a cell adhesion molecule expressed on the surface during a narrow window of B cell development, coincident with surface IgD. A ligand for CD22 has recently been identified on human T cells as the low molecular mass isoform of the leukocyte common Ag, CD45RO. CD22 has been reported to function in the regulation of both T and B cell activation in vitro. In this study, we report the isolation and expression of a molecular cDNA clone encoding the murine homologue of CD22, mCD22. Within their predicted protein sequences, murine and human sequences overall have 62% identity, which includes 18 of 20 extracellular cysteines and six of six cytoplasmic tyrosines. BHK cells transfected with mCD22 cDNA specifically adhere to resting and activated T lymphocytes and in addition bound activated, but not resting, B cells. Five Th clones were analyzed for their ability to adhere to mCD22; two Th0 clones and one Th1 clone bound CD22+ BHK transfectants, but not all T cell clones bound CD22+ cells: another Th1 clone and a Th2 clone did not. mCD22+ BHK transfectants were also specifically bound by the B cell-specific mAb, NIM-R6, demonstrating that this mAb is specific for murine CD22. Human cell lines expressing the counter-receptors for human CD22 were also examined for adhesion to the murine CD22 homologue; the epitope responsible for B cell adhesion to CD22 is conserved, whereas the T cell epitope binding to CD22 is not. The cDNA and mAb to murine CD22 will be useful for defining the in vivo function of CD22.