Serologic and molecular characterization of an abortigenic strain of equine arteritis virus isolated from infective frozen semen and an aborted equine fetus

A virus isolated from an aborted equine fetus was determined to be antigenically distinct from several other strains of equine arteritis virus (EAV) by use of a neutralization assay with a large panel of neutralizing monoclonal antibodies. The virus was readily neutralized by polyclonal equine anti-EAV serum. Comparative nucleotide and amino acid sequence analyses indicated that the virus (WA97) isolated from the aborted fetus was virtually identical to a virus (S1971) isolated from imported semen used to inseminate another mare on the farm. Phylogenetic analysis indicated that the WA97/S1971 virus was more related to European than to North American strains of EAV. These sensitive molecular procedures may be useful for epidemiologic investigations of EAV infections. Screening and certification of stallions and frozen equine semen would prevent dissemination of pathogenic strains of EAV.     

Overview of graduate medical education. Funding streams, policy problems, and options for reform

In this article, we examine the financing mechanisms for graduate medical education (GME) in the United States. In so doing, we identify Medicare as the single largest contributor to GME and the most important barrier to producing a physician workforce that is appropriately sized, balanced, and skilled. Until passage of the 1997 Budget Reconciliation Agreement, the structure of Medicare payments promoted overproduction and skewed production toward training specialists in tertiary settings. We then examine the various reform proposals put forward by major health care organizations and policy bodies. These organizations generally agree on seven policy objectives: Remove incentives that promote expanded resident production; Base the GME subsidy on actual costs and distribute it more uniformly; Focus reductions on specialty residency positions; Provide GME payments for training provided in ambulatory, community, and managed care sites; Decouple Medicare GME reimbursement from payments to health maintenance organizations for patient care; Require all health insurers to contribute to GME; and Ensure that reductions in the GME subsidy do not reduce access to care for low-income persons. A myriad of different mechanisms for achieving these objectives have been recommended, many of which could be melded together to form a comprehensive approach to GME reform. The prospects for meaningful GME reform are dim in the absence of broader Medicare reform. The costs to stake-holders are too concentrated while the benefits to the public are too diffuse for GME reform to stand alone. But the political imperative to deal with the federal budget's short-term deficit and Medicare's long-term solvency will likely create an opportunity for GME reform. An addendum has been added that shows how the 1997 Budget Reconciliation Agreement addresses most of the major reform objectives identified but that several important issues remain unresolved.     

Apolipoprotein E epsilon 4 allele distribution in alcoholic dementia and in Alzheimer's disease in Japan

The apolipoprotein E epsilon 4 allele has been associated with both familial and sporadic Alzheimer's disease (AD). Given its possible role in nerve repair and growth, it is plausible that apolipoprotein E may be a common denominator in the pathogenesis of several dementing diseases. Therefore, we investigated epsilon 4 frequencies in demented and nondemented alcoholics, as well as in patients with sporadic AD and controls in Japan. No significant differences in allele frequencies was found between demented and nondemented alcoholics and controls, while a significant association was demonstrated between AD and the epsilon 4 allele. These results support a specific role of epsilon 4 in the pathogenesis of AD, rather than a more general role for epsilon 4 in dementing illnesses.     

Definition and quantification of initial anthropogenic pollutant release in swimming pools

Pollutants, brought into a swimming pool by bathers, will react with chlorine to form disinfection by-products (DBPs). Some of these DBPs are found to be respiratory and ocular irritant and might be associated with asthma, or might even be carcinogenic. As DBPs in swimming pools are formed from bather-shed-pollutants, a reduction of these pollutants will lead to a reduction of DBPs. Until now, however, the release of pollutants by bathers has not been studied in detail. The study described in this paper focuses on the release of these pollutants, further called anthropogenic pollutants. The objective was to define and quantify the initial anthropogenic pollutants, by using a standardised shower cabin and a standardised showering protocol in laboratory time-series experiments and on-site experiments in swimming pools. The time-series experiments resulted in a definition of the initial anthropogenic pollutant release: the amount of pollutants released from a person in a standardised shower cabin during the first 60 s of showering. The data from the time-series experiments were used to create a model of pollutant release. The model can be used to predict the initial anthropogenic pollutant release as well as the effects of showering. On-site experiments were performed at four different swimming pools, including one outdoor pool. Results of these on-site showering experiments correspond with the time-series and model outcomes. Anthropogenic pollutant release (both chemical and microbiological) in swimming pool water can be reduced by pre-swim showering, very likely resulting in decreased DBPs formation and chlorine demand.     

CSF Biomarkers Reflecting Protein Pathology and Axonal Degeneration Are Associated with Memory,Attentional, and Executive Functioning in Early-Stage Parkinson′s Disease

In early-stage Parkinson′s disease (PD), cognitive impairment is common, and a variety of cognitive domains including memory, attention, and executive functioning may be affected. Cerebrospinal fluid (CSF) biomarkers are potential markers of cognitive functioning. We aimed to explore whether CSF α-synuclein species, neurofilament light chain, amyloid-β₄₂, and tau are associated with cognitive performance in early-stage PD patients. CSF levels of total-α-synuclein and phosphorylated-α-synuclein, neurofilament light chain, amyloid-β₄₂, and total-tau and phosphorylated-tau were measured in 26 PD patients (disease duration ≤5 years and Hoehn and Yahr stage 1–2.5). Multivariable linear regression models, adjusted for age, gender, and educational level, were used to assess the relationship between CSF biomarker levels and memory, attention, executive and visuospatial function, and language performance scores. In 26 early-stage PD patients, attention and memory were the most commonly affected domains. A higher CSF phosphorylated-α-synuclein/total-α-synuclein ratio was associated with better executive functioning (sβ = 0.40). Higher CSF neurofilament light was associated with worse memory (sβ = −0.59), attentional (sβ = −0.32), and executive functioning (sβ = −0.35). Reduced CSF amyloid-β₄₂ levels were associated with poorer attentional functioning (sβ = 0.35). Higher CSF phosphorylated-tau was associated with worse language functioning (sβ = −0.33). Thus, CSF biomarker levels, in particular neurofilament light, were related to the most commonly affected cognitive domains in early-stage PD. This indicates that CSF biomarker levels may identify early-stage PD patients who are at an increased risk of developing cognitive impairment.     

Monoclonal antibodies to a 100-kd protein reveal abundant A beta-negative plaques throughout gray matter of Alzheimer''s disease brains

Methionine metabolism and transmethylation are central to the metabolism and differentiation of all known cells. In enkaryotic organisms, methionine metabolism and transmethylation are of paramount importance in modification and regulation of proteins, lipids, and nucleic acids. The differential methylation of genes regulates their expression in the myriad of cells in eukaryotic organisms. Disruption and abnormalities in methionine metabolism and transmethylation seems to be associated with the major diseases of mankind, including cancer, heart disease, aging, obesity, and Parkinson's disease. In this review, we describe how aberrant and abnormal methionine metabolism and transmethylation are related to these major diseases. Most importantly, we review and hypothesize how the developing therapeutic recombination methioninase (rMETase) can be utilized to cure or prevent all of these diseases.     

Phosphorescence and optically detected magnetic resonance characterization of the environments of tryptophan analogues in staphylococcal nuclease, its V66W mutant, and Delta 137-149 fragment

Phosphorescence and optically detected magnetic resonance (ODMR) measurements are reported on the triplet states of the tryptophan analogues, 7-azatryptophan (7AW), 5-hydroxytryptophan (5HW), and 4-, 5-, and 6-fluorotryptophan (4FW, 5FW, 6FW), when incorporated at position 140 of wild-type Staphylococcal nuclease (7AW-nuclease, etc. ), positions 66 and 140 of its V66W mutant (7AW-V66W, etc.), and the deletion fragment of the latter, Delta 137-149 (7AW-V66W', etc.). These measurements point to the retention of protein structure at position 140 in each of the wild-type nuclease analogues. Substitution of the analogue at both tryptophan sites of V66W leads to structured sites with differentiated triplet-state properties for all analogues except 7AW-V66W, whose structure is destabilized. 5HW-V66W' is the only fragment that apparently lacks structure at position 66. All other V66W' analogues exhibit a structured environment at position 66 (4FW-V66W' was not studied), but in each case this site can be differentiated readily from the corresponding site in intact V66W. 7AW-V66W' is resolved by ODMR into two discrete structures with slightly differing zero field splittings (ZFS). Interaction of the protein with 5HW at position 66 of 5HW-V66W induces a 2-fold increase in the ZFS E parameter, which is reduced to its normal value upon formation of the fragment, 5HW-V66W'. Analogous effects occur for 5FW, but on a smaller scale.