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Biomedical subjects

A Pritchard

Publications and source records attributed to A Pritchard.

11 recordsLinked to original sources
PubMed1996

The structure of a highly virulent Theiler's murine encephalomyelitis virus (GDVII) and implications for determinants of viral persistence.

GDVII is a highly virulent Theiler's murine encephalomyelitis virus (TMEV) which causes acute encephalitis in mice, while the BeAn and DA strains are the less virulent TMEV which cause chronic demyelinating disease in the central nervous system as a result of persistent infection. Purified GDVII virus isolated from infected BHK-21 cells was crystallized and its structure was determined to 3.5-A resolution by X-ray crystallography. In contrast to other TMEV structures, the VP1 C-terminus of GDVII virus has an ordered conformation that forms a hook over the VP3 knob near the threefold axis. Comparisons with the atomic structures of the less virulent BeAn and DA viruses revealed significant structural variations in a major site (cluster B) on the protruding surface loop puff B of VP2. Puff B is located near the VP3 GH loop region which is structurally analogous to the host receptor attachment site of the major serogroup of human rhinoviruses. Mutations at residue 1101 in VP1 and residue 2141 in VP2, which are also near the VP3 GH loop and adjacent to cluster B, were previously shown to influence persistence of DA virus. These observations indicate that the characteristic interaction with the host receptor through these sites may potentially alter TMEV persistence.

Amino Acid Sequence↗
PubMed1993

A three-nucleotide insertion in the H stem-loop of the 5' untranslated region of Theiler's virus attenuates neurovirulence.

The highly structured 5' untranslated region (5' UTR) of Theiler's murine encephalomyelitis virus is involved in cap-independent translation of the viral RNA. Previously, we reported that the bicistronic mRNA chloramphenicol acetyltransferase-5' UTR-luciferase (Luc) efficiently expressed Luc both in a rabbit reticulocyte lysate and when transfected into BHK-21 cells. Insertion of 3 nucleotides at position 665 in the 5' UTR of this bicistronic mRNA resulted in greatly reduced Luc expression in BHK-21 cells but had little effect on expression of Luc in rabbit reticulocyte lysate. This mutation was also introduced into a virulent Theiler's murine encephalomyelitis virus chimera, Chi-VL. The kinetics of viral RNA and protein synthesis and virus production in BHK-21 cells were slower for the mutant chimera [Chi-VL(IN668)] than for Chi-VL; however, the final virus yields were comparable. Intracerebral inoculation of mice with the chimeras revealed that Chi-VL(IN668) was completely attenuated in neurovirulence. The reduced neurovirulence of Chi-VL(IN668) may be ascribed to its reduced growth in the central nervous system, most likely due to an impaired ability to synthesize viral proteins.

Animals↗
PubMed1992

Cloning and characterization of a gene from Bacillus stearothermophilus var. non-diastaticus encoding a glycerol dehydrogenase.

A 4.1-kb EcoRI fragment which includes the gene (gldA) encoding a glycerol dehydrogenase (G1DH; EC 1.1.1.6; glycerol:NAD oxidoreductase) from Bacillus stearothermophilus var. non-diastaticus has been cloned by virtue of its ability to restore glycerol utilisation to Escherichia coli glycerol kinase (glpK) and glycerol-3-phosphate dehydrogenase (glpD) mutants. Sequencing suggests that the gldA gene is likely to be monocistronic and encodes a protein of 39450 Da. The deduced amino acid composition and sequence of G1DH reveals that the protein is extremely similar to a characterized metal-dependent NAD-dependent G1DH from B. stearothermophilus RS93. The enzyme has limited homology to the iron-activated alcohol dehydrogenase of Zymomonas mobilis and the butanol dehydrogenase of Clostridium acetobutylicum.

Amino Acid Sequence↗
PubMed1991

Night studies for primary diurnal and nocturnal enuresis and preliminary results of the "clam" ileocystoplasty.

Modified conventional urodynamic apparatus was used to provide overnight monitoring of bladder and rectal pressure. A group of 26 patients with primary diurnal and nocturnal enuresis underwent both daytime rapid fill cystometry and overnight natural fill cystometry. The overnight study was effective in detecting detrusor instability in 10 patients deemed normal on rapid fill cystometry; 6 of these have now undergone clam ileocystoplasty and 5 are dry; 3 are awaiting this procedure. The clam remains very effective in the management of patients with resistant nocturnal and diurnal enuresis if careful selection is adopted. Overnight cystometry has proved to be an invaluable adjunct to the investigation of patients with primary diurnal and nocturnal enuresis previously felt to be urodynamically normal.

Adolescent↗
PubMed1982

Community-acquired bacteremic urosepsis in the elderly patients: a prospective study of 34 consecutive episodes.

A prospective study was done on the clinical, laboratory, radiological, immunological and therapeutic features of acute, symptomatic, bacteremic urosepsis in 34 consecutive, elderly patients who required hospitalization. Urinary tract infection was identified as the most common cause of gram-negative bacteremia in elderly patients admitted to a community hospital. Appropriate antibiotic therapy and a lack of serious associated medical illnesses contributed to the high survival rate. Bacteremia and shock occurring in the wake of pyelonephritis develop more commonly in elderly than in young women. In the elderly patient with bacteremia and pyelonephritis radiographic evaluation invariably demonstrates obstruction to urine flow, calculous disease or abscess. Guidelines are provided for the therapy of acute, symptomatic bacteremic urosepsis.

Aged↗
PubMed1982

Acute pyelonephritis in the elderly.

We did a prospective study of the clinical, laboratory, radiologic, and therapeutic features of acute, symptomatic, bacterial pyelonephritis in 35 consecutive elderly, noncatheterized patients who required hospitalization. Pyelonephritis had been identified as the most common cause of gram-negative bacteremia in elderly patients admitted to a community hospital. Appropriate antibiotic therapy and, of equal importance, a lack of serious associated medical illnesses contributed to the 97% survival. Two features appear to distinguish acute, symptomatic, bacterial pyelonephritis in elderly women from that in young women: an increased incidence of bacteremia and septic shock. We provide guidelines for the diagnostic evaluation and antibiotic therapy of acute, symptomatic, community-acquired, bacterial pyelonephritis in the elderly.

Acute Disease↗
PubMed1982

Symptomatic pyelonephritis in elderly men.

A prospective study was carried out of the clinical, laboratory, radiologic and therapeutic features of acute, symptomatic, bacterial pyelonephritis as experienced by 12 consecutive elderly, noncatheterized men who required hospitalization. In spite of the advanced ages of the men and the inordinate frequency of bacteremia and septic shock, no patient died. "Appropriate" antibiotic therapy, supportive treatment, and, as importantly, a lack of associated "imminently" or "ultimately" fatal illnesses contributed to the 100 per cent survival rate. Guidelines are provided for the diagnostic evaluation and antibiotic therapy of community-acquired pyelonephritis in elderly men.

Aged↗