Clinical trials in departments of internal medicine: ingredients for success.
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Clinical Trials as Topic↗
Biomedical subjects
A L Lewis
Publications and source records attributed to A L Lewis.
Structure and expression of the murine muscle adenylosuccinate synthetase gene.
A muscle-specific isoform of adenylosuccinate synthetase (AdSS1, EC) is one of three enzymes that constitute the purine nucleotide cycle, a muscle-specific metabolic cycle. Previously, we showed that the muscle Adss1 gene was highly expressed in both skeletal muscle and heart of the adult mouse. Here we have shown that the Adss1 gene is initially activated early in embryonic development in skeletal muscle and heart precursors and is subsequently up-regulated perinatally. The earliest detectable gene expression corresponds with the establishment of the first myogenic and cardiac lineages. To allow identification of the genetic signals controlling this developmental pattern of expression, the Adss1 gene was cloned and its structure determined. Transgenic analysis has shown that 1.9 kilobase pairs of 5' flank can activate expression in skeletal muscle progenitors and direct enhanced expression to adult cardiac muscle. Sequence analysis of the promoter and 5' flanking region revealed the presence of numerous potential muscle-specific cis-regulatory elements.
Adenine Nucleotides↗
Antibodies to St. Louis encephalitis virus in armadillos from southern Florida.
From January 1990 through March 1991, 189 armadillos (Dasypus novemcinctus) were collected from Brevard and Glades Counties in southern Florida (USA). The sera were analyzed for hemagglutination-inhibition (HAI) antibodies against St. Louis encephalitis (SLE) and eastern equine encephalomyelitis (EEE) viruses. None of the armadillos had detectable HAI antibody to EEE virus, but 59 (31%) had antibodies against SLE virus. Sera from 31 of the HAI-positive armadillos contained significant levels of neutralizing (NT) antibody to SLE virus. Armadillos captured during the 1990 SLE human epidemic in south Florida had a greater prevalence of HAI and NT antibody to SLE virus than did animals captured before the start of the epidemic. This is evidence that armadillos were fed on by mosquitoes infected with SLE virus. We propose that armadillos may be involved in the SLE amplification and transmission cycles in Florida.
Animals↗
Comparison of chickens and pheasants as sentinels for eastern equine encephalitis and St. Louis encephalitis viruses in Florida.
Pheasants and chickens were compared as sentinels for monitoring the transmission of arboviruses of public health significance in Florida during 1991-93. Results suggest that pheasants are better sentinels for eastern equine encephalitis (EEE) virus. They detected virus transmission 3-6 weeks earlier in epizootic years, 2-4 times more frequently during the season, and twice as many birds within a flock seroconverted during a given week. Pheasants detected virus transmission at 2 sites during 2 interepizootic years when chickens failed. Although pheasants detected St. Louis encephalitis (SLE) virus activity somewhat later than did chickens, they had greater seroconversion rates than did chickens. Although both bird species can be used to monitor EEE and SLE viruses, pheasants are more sensitive than chickens as sentinels for EEE virus and as sensitive as chickens as sentinels for SLE virus.
Animals↗
Lethality induced by a single site-specific double-strand break in a dispensable yeast plasmid.
Cells of the yeast Saccharomyces cerevisiae are delayed in the G2 phase of the cell cycle following chromosomal DNA damage. This arrest is RAD9-dependent and suggests a signaling mechanism(s) between chromosomal lesions and cell cycling. We examined the global nature of growth inhibition caused by an HO endonuclease-induced double-strand break (DSB) at a 45-bp YZ sequence (from MAT YZ) in a non-yeast region of a dispensable single-copy plasmid. The presence of an unrepaired DSB results in cellular death even though the plasmid is dispensable. Loss of cell viability is partially dependent on the RAD9 gene product. Following induction of the DSB, 40% of RAD+ and 49% of rad9 delta cells [including both unbudded (G1) and budded (S plus G2) cells] did not progress further in the cell cycle. The remaining RAD+ cells progressed to form microcolonies (< 30 cells) containing aberrantly shaped inviable cells. For the rad9 delta mutant, the majority of the remaining cells produced viable colonies accounting for the greater survival of the rad9 delta strain. Based on the profound effects of a single nonchromosomal DNA lesion, this system provides a convenient means for studying the signaling effects of a DNA lesion, as well as for designing strategies for modulating cell proliferation.
Cell Cycle↗
Identification of Highlands J virus from a Florida horse.
A virus, strain 64A-1519, isolated from the brain of a horse dying of encephalitis in Florida in 1964, was identified as western equine encephalomyelitis (WEE) virus. Recently, we used polyclonal and monoclonal immune reagents to identify this isolate by comparing it to 2 strains of WEE virus and to Highlands J (HJ) virus in hemagglutination-inhibition, immunofluorescent antibody, and plaque-reduction neutralization tests. These tests demonstrate that strain 64A-1519 is a strain of HJ virus distinct from WEE virus.
Alphavirus↗
Tonic-phasic-channel dichotomy and Crozier's law.
The constancy of the dynamic range in a luminance-discrimination task is known as Crozier's law; an old rule says that about half of a log unit spans the range from a low to a high frequency of seeing. For our conditions the slope of the psychometric function is steeper for short than for long test flashes; Crozier's law requires a different constant when temporal parameters change. This result is substantiated by an analysis of Massof's data [Vision Res. 21,995 (1981)] on the variation of the slope of psychometric curves for different wavelengths. The change in Crozier's constant between conditions may reflect the presence of more than one detection channel. If short test flashes are detected by phasic channels and long test flashes by both phasic and tonic channels, then our result implies a shorter dynamic range for phasic (Y-cell) than for tonic (X-cell) channels.
Computers↗
Light-curing resin systems.
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Composite Resins↗
Distribution of viruses associated with particles in waste water.
The distribution of solids-associated viruses in wastewater was studied to determine the effect of treatment processes on viruses associated with solids. Solids less than 0.3 micrometers in diameter were separated from the liquid phase of each sample by using a continuous-flow centrifuge. The percentage of virus associated with solids larger than 0.3 micrometers decreased from 28% in the influent to 3.4% in unchlorinated effluent, and this was accompanied by a 92% decrease in the total concentration of virus. These results indicate that the original solids-associated virus as well as that is secondarily adsorbed to mixed liquor-suspended solids is lost during clarification. The total concentration of virus was reduced by 82% by chlorination, and the percentage of virus associated with solids increased to 7.7% upon chlorination, indicating some protection due to association with particles larger than 0.3 micrometers. When a suspension of fecal particles and a 0.22-micrometers filtrate of a fecal homogenate were sonicated, a threefold increase in virus titer was observed in each. This demonstrated that viruses may be attached to particles smaller than 0.22 micrometers. Thus, small viral aggregates or viruses attached to submicron particles represented the major portion of solids-associated virus in treated sewage.
Chlorine↗
Human enteroviruses and wildlife: isolation from gray squirrels.
Five isolates of human echovirus 1/8 complex were recovered from the feces of free-ranging gray squirrels. The source of infection and the significance of the isolates remain unknown.
Animals↗
Survival of poliovirus within organic solids during chlorination.
Poliovirus in fecal homogenates was used to determine the protection against inactivation by chlorination afforded virus that was occluded within particulates. Virus that was closely associated with or occluded within small fecal particulates was protected. A fourfold increase in combined residual chlorine was required to achieve the same degree of inactivation for occluded virus as for free or secondarily adsorbed virus. A combined chlorine residual of 6.6 mg/liter was necessary to achieve 50% inactivation in 15 min at pH 8.0 and 22 degrees C in a particulate suspension containing occluded virus compared to 1.4 mg/liter for free virus. These differences were found to be relatively small compared to differences due to the presence of dissolved organics or between free and combined chlorine residuals. The results suggest different mechanisms of protection due to adsorption and occlusion.
Adsorption↗
Encephalomyocarditis virus infection of captive elephants.
Four African elephants at each of 2 widely separated zoologic gardens in Florida died following a fulminating illness. Tissue suspensions obtained from an elephant from each of the zoologic gardens were inoculated into newborn mice, 3- to 4-week-old mice, and buffalo green monkey and baby hamster kidney cell cultures. Encephalitis and myocarditis developed in the mice. The cell cultures were destroyed within 24 to 72 hours, and intracytoplasmic viral inclusions were observed in infected cells by electron microscopy. The viral agent was neutralized by known antiserum to encephalomyocarditis virus.
Animals↗
Isolation and identification of pathogenic Naegleria from Florida lakes.
Five cases of primary amoebic meningoencephalitis associated with swimming in freshwater lakes have been recorded in Florida over the past 14 years. The present study demonstrated that pathogenic Naegleria, the causative agent, is relatively widespread. Twelve of 26 lakes sampled only once yielded the amoeba. Populations in three of five lakes sampled routinely reached levels of one amoeba per 25 ml of water tested during the hot summer months. Overwintering in freshwater lake bottom sediments was demonstrated, showing that thermal-discharge pollution of waters plays a miniscule, if any, role in the maintenance of pathogenic Naegleria in nature in this semitropical area.
Animals↗
Demonstration of solids-associated virus in wastewater and sludge.
Data presented demonstrate the relatively high multiplicity of solids-associated virus in field samples, i.e., wastewater, sludge, and soils. Influent, effluent, and chlorinated effluent samples showed 16.1 to 100% of the total virus demonstrated in samples to be solids associated. Three techniques for freeing solids-associated virus are described and compared. Using sonication of solids and polyethylene glycol concentration, virus was demonstrated in fully digested sludge (60 days at 34 C), sand at the site of a sewer leak, and dried sludge cake and mud 900 m downstream from a sewage disposal site. These data emphasize the inadequacy of virus concentration techniques that do not include the processing of solids. In situ elution failed to free solids-associated virus.
Chlorofluorocarbons, Methane↗
Demonstration of virus in groundwater after effluent discharge onto soil.
The survival of virus present in secondary effluents discharged into a cypress dome was studied. Isolations were made from concentrates of water drawn from 10-foot (304.80 cm) deep wells. Data presented show vertical and lateral virus movement as well as survival within the dome for 28 days during a period of heavy rains when no effluent was being applied. Due to the inefficiency of virus concentration procedures, it is proposed that much of the virus present was probably not demonstrated. A rapid, relatively inexpensive concentration technique for sewage influents and effluents is discussed.
Animals↗