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Biomedical subjects

A J Howard

Publications and source records attributed to A J Howard.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1988

The prevalence of antibiotic resistance in Haemophilus influenzae in Wales. Report from the Standing Specialist Advisory Group for Microbiology in Wales.

From January to April 1986 all 21 Clinical Microbiology Laboratories in Wales took part in a survey to determine the prevalence of antibiotic resistance in Haemophilus influenzae. All isolates were collected and despatched to a central laboratory where identification was confirmed and antibiotic sensitivity tests repeated. One thousand four hundred and forty strains were available for analysis. Resistance was present in 128 (8.9%) to ampicillin, 23 (1.6%) to cefaclor, 28 (1.7%) to chloramphenicol, 282 (19.6%) to erythromycin, 43 (3.0%) to tetracycline, 90 (6.2%) to sulphonamide and 66 (4.6%) to trimethoprim. One hundred and twenty-one strains (8.4%) were beta-lactamase producers. Thirteen (0.9%) were resistant to four or more antibiotics and included one type b strain isolated from cerebrospinal fluid resistant to ampicillin, chloramphenicol, tetracycline, trimethoprim and sulphonamide. The prevalence of resistance to ampicillin and trimethoprim was higher than that recorded previously in two large studies elsewhere in the United Kingdom. Ampicillin resistance was more common in strains from hospital inpatients than those from general practice.

Drug Resistance, Microbial↗
PubMed1988

The in-vitro activity of CP-62,993 against Haemophilus influenzae, Branhamella catarrhalis, staphylococci and streptococci.

The in-vitro activity of a new macrolide antibiotic CP-62,993 (Pfizer Ltd) was determined for 420 bacterial isolates, comprising 150 Haemophilus influenzae, 48 Branhamella catarrhalis, 50 Staphylococcus aureus, 50 coagulase negative staphylococci, 50 beta-haemolytic streptococci, 50 Streptococcus pneumoniae and 22 oral streptococci. CP-62,993 was compared with erythromycin and penicillin (ampicillin in the case of H. influenzae). The MICs of CP-62,993 were found to be lower than those of erythromycin for the two Gram-negative species tested: this was particularly marked in the case of H. influenzae where a ten-fold difference in the MIC50 was observed (CP-62,993, 0.25 mg/l, erythromycin 2 mg/l). In general MICs of CP-62,993 were two-fold higher than those of erythromycin for the Gram-positive species studied, with the exception of the oral streptococci which were equally susceptible (MIC50 0.03 mg/l) to both macrolides. Activity similar to that of erythromycin was observed against Str. pneumoniae (MIC values 0.015-0.12 mg/l), Staph. aureus (MIC 0.12-1 mg/l) and beta-haemolytic streptococci (MIC 0.06-4 mg/l). Incubation in a CO2 enriched atmosphere decreased activity of both erythromycin and CP-62,993. The effect was more marked for CP-62,993, the MIC50s of all groups of organisms being increased four-fold when they were incubated in the presence of 5 or 10% CO2.

Azithromycin↗
PubMed1988

Comparative in-vitro activity of a new oral carbacephem, LY163892.

The in-vitro activity of a new oral carbacephem, LY163892, was compared with cefaclor, cephalexin, cephradine, cefadroxil and selected penicillins against 529 bacterial isolates. LY163892 exhibited greater activity in vitro than all four cephalosporins against Haemophilus influenzae, beta-lactamase producing Branhamella catarrhalis, Escherichia coli, Klebsiella spp. and Proteus mirabilis. LY163892 had equivalent potency to cefaclor against non-beta-lactamase producing B. catarrhalis, streptococci and Staphylococcus aureus. Group D beta-haemolytic streptococci, Proteus vulgaris, and methicillin-resistant staphylococci were universally resistant to LY163892 and the four cephalosporins. Broth dilution experiments indicated that LY163892 was bactericidal against a range of Gram-positive and Gram-negative organisms and suggested that the antibiotic had a similar degree of stability to the beta-lactamases of H. influenzae, B. catarrhalis and Staph. aureus as did cefaclor. The susceptibility of 16 strains of H. influenzae to LY163892 and cefaclor were equivalent when estimated using three different commercially available agar media. Addition of carbon dioxide to the incubation atmosphere significantly reduced the potency of both drugs.

Bacteria↗
PubMed1987

Crystal structures of metyrapone- and phenylimidazole-inhibited complexes of cytochrome P-450cam.

The crystal structures of metyrapone- and 1-, 2-, and 4-phenylimidazole-inhibited complexes of cytochrome P-450cam have been refined to a nominal resolution of 2.1 A and compared with the 1.63-A camphor-bound structure. With the exception of 2-phenylimidazole, each of the inhibitors forms an N-Fe bond with the heme iron atom while part of the inhibitor sits in the camphor-binding pocket. In the 2-phenylimidazole complex, a water molecule or hydroxide ion coordinates with the heme iron atom while the inhibitor binds in the camphor pocket adjacent to the aqua ligand. Each of the inhibitors forces the central region of helix I that forms part of the O2 binding pocket to move away from the inhibitor, with the exception of 2-phenylimidazole where the helix moves in toward the inhibitor. In addition, the Tyr-96 region, which provides specific contact points with the substrate, is perturbed, although to varying degrees with each inhibitor. These perturbations include large, localized changes in Debye-Waller or temperature factors, indicative of changes in dynamical fluctuations. The largest inhibitor, metyrapone, causes the fewest changes, while 2-phenylimidazole binding causes the largest, especially in helix I. The large 2-phenylimidazole-induced movement of helix I can be rationalized on the basis of the inhibitor imidazole group's hydrogen-bonding requirements.

Camphor 5-Monooxygenase↗
PubMed1987

Cocrystals of yeast cytochrome c peroxidase and horse heart cytochrome c.

Yeast cytochrome c peroxidase and horse heart cytochrome c have been cocrystallized in a form suitable for x-ray diffraction studies and the structure determined at 3.3 A. The asymmetric unit contains a dimer of the peroxidase which was oriented and positioned in the unit cell using molecular replacement techniques. Similar attempts to locate the cytochrome c molecules were unsuccessful. The peroxidase dimer model was subjected to eight rounds of restrained parameters least squares refinement after which the crystallographic R factor was 0.27 at 3.3 A. Examination of a 2Fo-Fc electron density map showed large "empty" regions between peroxidase dimers with no indication of cytochrome c molecules. Electrophoretic analysis of the crystals demonstrated the presence of the peroxidase and cytochrome c in an approximate equal molar ratio. Therefore, while cytochrome c molecules are present in the unit cell they are orientationally disordered and occupy the space between peroxidase dimers.

Animals↗
PubMed1987

High-resolution crystal structure of cytochrome P450cam.

The crystal structure of Pseudomonas putida cytochrome P450cam with its substrate, camphor, bound has been refined to R = 0.19 at a normal resolution of 1.63 A. While the 1.63 A model confirms our initial analysis based on the 2.6 A model, the higher resolution structure has revealed important new details. These include a more precise assignment of sequence to secondary structure, the identification of three cis-proline residues, and a more detailed picture of substrate-protein interactions. In addition, 204 ordered solvent molecules have been found, one of which appears to be a cation. The cation stabilizes an unfavorable polypeptide conformation involved in forming part of the active site pocket, suggesting that the cation may be the metal ion binding site associated with the well-known ability of metal ions to enhance formation of the enzyme-substrate complex. Another unusual polypeptide conformation forms the proposed oxygen-binding pocket. A localized distortion and widening of the distal helix provides a pocket for molecular oxygen. An intricate system of side-chain to backbone hydrogen bonds aids in stabilizing the required local disruption in helical geometry. Sequence homologies strongly suggest a common oxygen-binding pocket in all P450 species. Further sequence comparisons between P450 species indicate common three-dimensional structures with changes focused in a region of the molecule postulated to be associated with the control of substrate specificity.

Amino Acid Sequence↗