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Biomedical subjects

A J Howard

Publications and source records attributed to A J Howard.

At least 19 recordsLinked to original sources
PubMed1992

1.67-A X-ray structure of the B2 immunoglobulin-binding domain of streptococcal protein G and comparison to the NMR structure of the B1 domain.

The structure of the B2 immunoglobulin-binding domain of streptococcal protein G has been determined at 1.67-A resolution using a combination of single isomorphous replacement (SIR) phasing and manual fitting of the coordinates of the NMR structure of B1 domain of streptococcal protein G [Gronenborn, A. M., et al. (1991) Science 253, 657-661]. The final R value was 0.191 for data between 8.0 and 1.67 A. The structure described here has 13 residues preceding the 57-residue Ig-binding domain and 13 additional residues following it, for a total of 83 residues. The 57-residue binding domain is well-determined in the structure, having an average B factor of 18.0. Only residues 8-77 could be located in the electron density maps, with the ends of the structure fading into disorder. Like the B1 domain, the B2 domain consists of four beta-strands and a single helix lying diagonally across the beta-sheet, with a -1, +3 chi, -1 topology. This small structure is extensively hydrogen-bonded and has a relatively large hydrophobic core. These structural observations may account for the exceptional stability of protein G. A comparison of the B2 domain X-ray structure and the B1 domain NMR structure showed minor differences in the turn between strands and two and a slight displacement of the helix relative to the sheet. Hydrogen bonds between crystallographically related molecules account for most of these differences.

Amino Acid Sequence↗
PubMed1992

Cloning and characterization of the rat glutathione peroxidase gene.

The increased activity of glutathione peroxidase (GSHPx) in rat lungs is associated with the development of tolerance of the animals to hyperoxia. To understand further the regulation of expression of this enzyme, the molecular structure of the corresponding rat gene was characterized. The rat GSHPx gene consists of two exons interrupted by a single intron of 217 base pairs. The same initiation sites for transcription were found to be utilized in both lung and liver. The promoter of the GSHPx gene contains neither a 'TATA' box nor a 'CAAT' box. Instead, it comprises two copies of Sp1 binding motif and one copy of AP-2 binding motif. These features of the promoter may offer a clue to the mechanisms by which the expression of this gene is controlled.

Amino Acid Sequence↗
PubMed1992

A survey of invasive Haemophilus influenzae infections.

A survey of invasive H. influenzae infections has been underway in six regions of England and Wales since September 1990. In the first year, there were 433 cases of which 362 (84%) were due to H. influenzae type b (Hib). The majority of Hib infections were in children aged less than 5 years; there being an annual incidence of 26.4/100,000 in this age group. Meningitis occurred in 56% of cases of Hib infection. The results confirm previous evidence of the need to incorporate Hib vaccination into the childhood immunisation schedule. The ongoing survey data will provide useful information to assess the impact of an Hib immunisation programme.

Adolescent↗
PubMed1991

Epidemiology of Haemophilus influenzae type b invasive disease in Wales.

OBJECTIVE: To investigate the epidemiology of invasive disease due to Haemophilus influenzae type b, the clones responsible, and the antibiotic resistance of the isolates. DESIGN: Prospective population based analysis of clinical and epidemiological data collected for Gwynedd during 1980-90 and in the whole of Wales during 1988-90. SETTING: 19 hospitals in Wales; all medical microbiology laboratories in Wales participated. PATIENTS: 82 patients with confirmed invasive infections caused by H influenzae type b in Gwynedd during 1980-90 and 207 in Wales during 1988-90. MAIN OUTCOME MEASURES: Clinical and epidemiological measures; analysis of the clonal types of the isolates based on the electrophoretic mobilities of 17 metabolic enzymes; and antibiotic resistance. RESULTS: The annual incidence of H influenzae type b infections in Gwynedd was 3.2 cases/100,000 and in Wales was 2.5 cases/100,000. Most cases occurred in children aged under 5 years, the highest annual incidence being in those aged under 1 (84.6/100,000 and 56.9/100,000 in Wales). The cumulative risk of acquiring H influenzae type b disease by the fifth birthday was one in 456 in Gwynedd and one in 578 in Wales. Fifteen per cent of cases in Gwynedd and 7% of those in Wales occurred in adults. Predominant clinical conditions were meningitis in children and pneumonia in adults. In Gwynedd 2/70 (3%) children and 5/12 (42%) adults died. Long term neurological sequelae occurred in 8% (4/48) of children who survived haemophilus meningitis. Children presenting with infection were usually the youngest members of their family. No secondary household cases were identified. 100 of 128 (78%) strains were of a single clone, electrophoretic type 12.5, and 4/207 (1.9%) isolates from Wales were resistant to both ampicillin and chloramphenicol. CONCLUSIONS: The annual rate of infection in children aged under 5 in four Welsh counties was 12-44% higher than that previously published for the United Kingdom. The study emphasises the potential value of a vaccine effective in early infancy and provides baseline data to assess its efficacy after its introduction. Alternatives to ampicillin and chloramphenicol should be used as first line, empirical treatment for severe infections that might be caused by H influenzae type b in Wales.

Adolescent↗
PubMed1991

A metal-mediated hydride shift mechanism for xylose isomerase based on the 1.6 A Streptomyces rubiginosus structures with xylitol and D-xylose.

The crystal structure of recombinant Streptomyces rubiginosus D-xylose isomerase (D-xylose keto-isomerase, EC 5.3.1.5) solved by the multiple isomorphous replacement technique has been refined to R = 0.16 at 1.64 A resolution. As observed in an earlier study at 4.0 A (Carrell et al., J. Biol. Chem. 259: 3230-3236, 1984), xylose isomerase is a tetramer composed of four identical subunits. The monomer consists of an eight-stranded parallel beta-barrel surrounded by eight helices with an extended C-terminal tail that provides extensive contacts with a neighboring monomer. The active site pocket is defined by an opening in the barrel whose entrance is lined with hydrophobic residues while the bottom of the pocket consists mainly of glutamate, aspartate, and histidine residues coordinated to two manganese ions. The structures of the enzyme in the presence of MnCl2, the inhibitor xylitol, and the substrate D-xylose in the presence and absence of MnCl2 have also been refined to R = 0.14 at 1.60 A, R = 0.15 at 1.71 A, R = 0.15 at 1.60 A, and R = 0.14 at 1.60 A, respectively. Both the ring oxygen of the cyclic alpha-D-xylose and its C1 hydroxyl are within hydrogen bonding distance of NE2 of His-54 in the structure crystallized in the presence of D-xylose. Both the inhibitor, xylitol, and the extended form of the substrate, D-xylose, bind such that the C2 and C4 OH groups interact with one of the two divalent cations found in the active site and the C1 OH with the other cation. The remainder of the OH groups hydrogen bond with neighboring amino acid side chains. A detailed mechanism for D-xylose isomerase is proposed. Upon binding of cyclic alpha-D-xylose to xylose isomerase, His-54 acts as the catalytic base in a ring opening reaction. The ring opening step is followed by binding of D-xylose, involving two divalent cations, in an extended conformation. The isomerization of D-xylose to D-xylulose involves a metal-mediated 1,2-hydride shift. The final step in the mechanism is a ring closure to produce alpha-D-xylulose. The ring closing is the reverse of the ring opening step. This mechanism accounts for the majority of xylose isomerase's biochemical properties, including (1) the lack of solvent exchange between the 2-position of D-xylose and the 1-pro-R position of D-xylulose, (2) the chemical modification of histidine and lysine, (3) the pH vs. activity profile, and (4) the requirement for two divalent cations in the mechanism.

Aldose-Ketose Isomerases↗
PubMed1991

Relapsing Salmonella enteritidis infection in a young adult male with chronic granulomatous disease.

A case of chronic Salmonella enteritidis infection in a young adult patient is reported. Following an initial enteritis with bacteraemia, the illness lasted for a 7-year period and was characterized by recurrent pyrexia, anaemia, weight loss and marked hepatosplenomegaly. Investigations revealed that the patient suffers from a mild form of chronic granulomatous disease presenting in adolescence.

Adult↗
PubMed1991

Molecular structure of a functional rat gene for manganese-containing superoxide dismutase.

The manganese-containing superoxide dismutase (MnSOD) constitutes one of the major cellular defense mechanisms against the toxic effects of superoxide radical. The development of tolerance in adult rats to lethal exposure of O2 (100%) after pre-exposing them to a sublethal concentration of O2 (85%) was found to be closely associated with the increased activity of this enzyme in the lungs. Further experiments have shown that the transcriptional rate of the gene coding for MnSOD in rat lungs is increased at day 3 of 85% O2 exposure. To elucidate the nature of this transcriptional activation during hyperoxic insults, we chose to first understand the structure of the rat MnSOD gene. Three overlapping rat genomic fragments were isolated, and the DNA sequence containing the whole MnSOD gene was completely determined. The rat MnSOD gene contains at least five exons and is located in one piece of 16.4-kb EcoRI genomic DNA fragment. However, Southern blot analysis of total rat genomic DNA probed with MnSOD cDNA revealed an additional hybridizing 8.6-kb EcoRI genomic fragment besides the 16.4-kb one. To clarify the origin of this unexpected hybridizing genomic fragment, three unique genomic sequences derived from the promoter, intron 2, and the 3' untranslated region of the genomic clones were used to rehybridize the same Southern blot filter and were found to only hybridize to the 16.4-kb but not 8.5-kb EcoRI genomic fragment. These data suggest: (1) two MnSOD genes are present per haploid rat genome, and (2) all three cloned genomic fragments are derived from the MnSOD gene, which is located in the 16.4-kb EcoRI genomic fragment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Can stress be measured with an anxiety questionnaire?

The general problem of stress assessment and the role of anxiety state is considered using a widely accepted theoretical model of stress. The need for clear conceptualizations of stress production and stress response factors is indicated, to avoid confusion between measurements taken from instruments assessing anxiety state and emotional stress response.

Anxiety↗
PubMed1989

Bacteriology of otitis media with effusion.

A study was undertaken to evaluate the prevalence and antibiotic susceptibility of bacteria present in the middle ear of patients with otitis media with effusion. Middle ear effusions (MEE), nasopharyngeal and throat swabs were obtained at operation and cultured for aerobic and anaerobic bacteria. Two hundred and fifty-nine effusions were obtained from 152 subjects examined. Haemophilus influenzae was isolated from 32 (12.3 per cent) effusions, Streptococcus pneumoniae from seven (2.7 per cent), Staphylococcus aureus from seven (2.7 per cent), Branhamella catarrhalis from one (0.4 per cent)--Group A beta haemolytic streptococci from one (0.4 per cent) and Staphylococcus epidermidis from three (1.9 per cent). The occurrence of respiratory pathogens in MEE reflected their prevalence in the upper respiratory tract. Significantly fewer children who had received antibiotics prior to surgery had organisms present in the MEE. Eight and a half per cent of H. influenzae and 64 per cent of B. catarrhalis were resistant to ampicillin. The present study confirms that bacteria are present in the middle ear in a significant number of patients with otitis media with effusion.

Adolescent↗
PubMed1989

The prevalence of antibiotic resistance in Haemophilus influenzae in Ireland.

From January to April 1988, 36 clinical microbiology laboratories in Northern Ireland and Eire took part in a survey to determine the prevalence of antibiotic resistance in Haemophilus influenzae. All isolates were collected and despatched to a coordinating laboratory where identification was confirmed and antibiotic sensitivity tests repeated. One thousand seven hundred and ninety strains were available for analysis. Of these, 10.9% were resistant to ampicillin (10.2% being beta-lactamase producers), 0.4% to amoxycillin-clavulanate, 2.1% to cefaclor, 3.7% to chloramphenicol, 2.6% to erythromycin, 4.1% to tetracycline, 2.6% to sulphonamide and 5.1% to trimethoprim. One hundred and nine strains (6.3%) were resistant to two or more of the antibiotics tested and 31 (1.7%) exhibited combined resistance to ampicillin, chloramphenicol and tetracycline. The prevalence of resistance to ampicillin and chloramphenicol was higher than had been previously recorded in largescale studies conducted on the British mainland.

Anti-Bacterial Agents↗
PubMed1988

Salmonella enteritidis phage type 4 infection: association with hen's eggs.

Epidemiological and microbiological investigation of the four outbreaks of Salmonella enteritidis phage type (PT) 4 that occurred in Wales in 1988 implicated foods containing shell eggs from hens as the vehicle of infection. In a case-control study of sporadic cases there was a significant association between infection and egg consumption in the 3 days before illness. These findings provide data to support the warnings from the Departments of Health in the United Kingdom about risks of infection from eating raw or undercooked hens' eggs.

Adult↗
PubMed1988

Infection control organization in hospitals in England and Wales, 1986. Report of a survey undertaken by a Hospital Infection Society working party.

Questionnaires were distributed to hospitals in order to obtain information regarding arrangements for infection control. Returns were obtained from 180 of 200 (90%) health districts in England and Wales covering 95% of 'acute' and 85% of 'other' hospital beds listed in the Hospitals Year Book. The results demonstrated that some form of infection control organization was present in all districts, 98% had control of infection officers and 92% control of infection committees. The proportion of health districts with an infection control nurse had risen from 64% in 1979 to 89%, and the regional variation seen in 1979 was no longer marked. The major commitment of medical microbiologists to infection control was underlined.

Cross Infection↗
PubMed1988

Nasopharyngeal carriage and antibiotic resistance of Haemophilus influenzae in healthy children.

An investigation was undertaken to determine the isolation rate and antibiotic resistance of Haemophilus influenzae from the nasopharynx of young children. The 996 subjects studied were up to 6 years of age. H. influenzae was isolated from 304 (30.5%) and strains of capsular type b from 11 (1.1%). Age, sibling status, season, respiratory infection and antibiotic therapy all influenced isolation rates. The overall prevalence of antibiotic resistance in the strains isolated was ampicillin 5.4% (all beta-lactamase producers), cefaclor 0.3%, chloramphenicol 1.3%, erythromycin 38.2%, tetracycline 1.3%, trimethoprim 5.4% and sulphamethoxazole 0%. Ampicillin resistance was more common in type b than non-capsulated strains.

Aging↗