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Biomedical subjects

P Williams

Publications and source records attributed to P Williams.

At least 343 records · Page 19Linked to original sources
PubMed1992

General pharmacology of pergolide in animals. 1st communication: cardiovascular, respiratory and autonomic nervous system studies.

Pergolide mesylate ((8 beta)-8-[(methylthio)methyl]-6-propylergoline monomethanesulfonate, LY 127,809, CAS 66104-23-2) is a novel and potent dopamine agonist marketed for treating the symptoms of Parkinson's disease. The potential secondary pharmacological effects of this agent on the cardiovascular, respiratory, and the autonomic nervous systems were examined. Pergolide exhibited significant pharmacological effects in cardiovascular and autonomic tests at high oral or intravenous doses. The reference dopamine agonist, bromocriptine, exhibited effects qualitatively similar to, but at doses generally higher than, pergolide, in parallel with its lower therapeutic potency relative to pergolide. In summary, these studies confirm the pharmacological selectivity of pergolide at low doses, and indicate the potential for secondary pharmacological side effects upon cardiovascular function at significant multiples of the clinical dose.

Acetylcholine↗
PubMed1991

Failure to deliver hepatitis B vaccine: confessions from a genitourinary medicine clinic.

OBJECTIVE: To audit hepatitis B immunisation of homosexual or bisexual men in a genitourinary medicine clinic. DESIGN: Retrospective case note review of all homosexual and bisexual men presenting to a genitourinary clinic as new patients during 12 months in 1988 and follow up review of notes to May 1990. SETTING: One department of genitourinary medicine, Middlesex Hospital. PATIENTS: 758 homosexual or bisexual men, of whom 207 started a course of hepatitis B vaccine in 1988. Case notes were unavailable for one patient. MAIN OUTCOME MEASURES: The proportion of patients screened for hepatitis B virus markers, the proportion of susceptible patients immunised, the proportion completing the vaccine course, and the proportion rendered immune. RESULTS: 25 men had been previously tested for hepatitis markers; of the 732 not previously tested, 440 (60.1%) were screened for hepatitis B markers. 207 (69%) of the 300 patients without hepatitis B serological markers started the vaccine course, and 141 (68%) completed it, with 75 (84%) of the 89 tested after immunisation being immune. An estimated 24% of susceptible new patients were rendered immune as a result of the immunisation policy. Patients who presented with a further episode of a sexually transmitted disease were more likely to have been screened (25% v 12%, p less than 0.0001) and immunised (31% v 18% p = 0.02); those known or found to be positive for HIV antibody were more likely to have been screened (23% v 14%, p = 0.047) but less likely to have been immunised (6% v 17%, p = 0.004). CONCLUSIONS: The major failure was that in not screening; failure to immunise patients found to be susceptible and failure of compliance with the vaccine course contributed. Non-response to the vaccine was of minor importance. Improvements in vaccine delivery are required. IMPLICATIONS: Other providers should be encouraged to review their performance.

Adult↗
PubMed1991

Irreversible inactivation of beta-lactamase I from Bacillus cereus by chlorinated 6-spiroepoxypenicillins.

On incubation of the chlorinated 6-spiroepoxypenicillin anilides (I) and (II) [formula: see text] with beta-lactamase 1 from Bacillus cereus, three distinct processes are observed. The inhibitors act as (a) substrates, the turnover of which respectively results in a single product, namely 6-substituted 2(H)-3,4-dihydro-1,4-thiazine, (b) a transiently inhibited enzyme complex, and finally (c) an irreversibly inactivated enzyme complex. Although differing only in their stereochemistry at one centre, the anilide (K) is a more potent irreversible inactivator of beta-lactamase I than is compound (II). Analysis of irreversibly inactivated beta-lactamase I by isoelectric focusing and inspection of peptide fragmentation maps indicated that irreversible inactivation appears to be accompanied by covalent modification. These studies reveal that the chlorinated 6-spiroepoxypenicillin anilide (I) is a mechanism-based beta-lactamase inhibitor.

Bacillus cereus↗
PubMed1991

Identification of two distinct nuclear factors with DNA binding activity within the glucocorticoid regulatory region of the rat alpha-1-acid glycoprotein promoter.

Efficient glucocorticoid induction of alpha-1-acid glycoprotein (AGP) mRNA in rat hepatoma cells HTC (JZ-1) requires the activity of one or more preexisting and labile proteins acting cooperatively with the glucocorticoid receptor. Inhibiting protein synthesis markedly diminishes the glucocorticoid induction of rat AGP mRNA without affecting the inducibility of other glucocorticoid inducible genes such as the mouse mammary tumor virus (MMTV) or tyrosine amino transferase (TAT). The sequences responsible for conferring glucocorticoid inducibility to the rat AGP gene have localized on the AGP promoter between nucleotides -121 and -42. A typical glucocorticoid regulatory element (GRE) is found between residues -121 and -105 and downstream of this are the sequences (-90 to -42) responsible for the cycloheximide inhibition of the hormonal induction (10). Using mobility shift assays we have characterized the binding of two proteins or complexes of proteins to this promoter region (-90 to -64). Our data show that the binding of these factors (called ANF-1 and ANF-2) to the DNA is highly specific, and is not directly affected by cycloheximide. Furthermore a second binding site for ANF-2 has been localized in the AGP regulatory region to a sequence that overlaps the GRE.

Animals↗
PubMed1991

Isolation and characterisation of Haemophilus influenzae type b mutants defective in transferrin-binding and iron assimilation.

The quinone antibiotic streptonigrin was used to select mutants of Haemophilus influenzae type b defective in human transferrin binding. Compared with the parent wild-type strain (JKP1), mutant JKP5 was unable to bind transferrin whilst mutant JKP4 showed reduced binding. JKP5 appeared to lack an approximately 72 kDa transferrin-binding protein. Unlike JKP1, neither JKP4 nor JKP5 were able to acquire iron from human transferrin but their ability to use a variety of other iron and haem compounds as iron sources was unaffected. Such mutants should prove useful in further elucidating the mechanism of transferrin iron-acquisition and its contribution to the virulence of H. influenzae.

Carrier Proteins↗
PubMed1991

Geographical and urban-rural variation in the seasonality of suicide: some further evidence.

The seasonal variation of the suicides (n = 57,007) that occurred in Italy during the years 1969-1984 was evaluated using harmonic analysis, according to the method described by Pocock (1974). Monthly data were analyzed, separately for males and females, taking into account the setting (urban or rural) and the geographical location (Northern, Central or Southern regions). As compared with a previous study by our research group, a more precise (less aggregated) index of the urban-rural continuum was used. Rates for males were greater than those for females; urban were higher than rural rates; the seasonality was greater in the rural than in the urban settings and generally greater in males than in females in the Southern as well as in the Northern regions.

Cross-Sectional Studies↗
PubMed1991

Abnormalities in the glycosylation of IgG in spouses of patients with rheumatoid arthritis. A family study.

Forty-seven members of eight families with a rheumatoid proband were analysed for abnormal glycosylation of IgG. The results (%G(o) which is the percentage of oligosaccharide chains lacking galactose) were corrected for age and expressed as SD units about the mean for the normal population. Seven of 8 probands, 3/8 spouses, 3/5 RA relatives and 4/26 non-RA relatives had %G(o) values greater than 1SD above the age corrected mean for the normal control population (P less than 0.001, less than 0.01, less than 0.005 and greater than 0.5 respectively). A further 13 spouse pairs were studied. Ten of 13 probands and 8/13 spouses had %G(o) values greater than 1SD above the mean (P less than 0.001 and less than 0.001 respectively). Thus in total, a strikingly high number of unaffected spouses had high %G(o) values (11/21). IgM, IgA and IgG rheumatoid factors were studied. While RA patients' sera showed a correlation between IgM and IgA rheumatoid factors and %G(o), (IgM, r = 0.41 0.05 greater than P greater than 0.02, IgA, r = 0.36, P = 0.05), no correlation between IgG RF and %G(o) was noted in the RA patients. No correlation was found between any of the RF classes and %G(o) in spouses and non-RA relatives.

Arthritis, Rheumatoid↗
PubMed1991

Use of an electron beam for post-mastectomy radiotherapy: 5-year follow-up of 500 cases.

Since 1982, the standard method of postmastectomy regional radiotherapy at the Christie Hospital has been to use a single electron field of fixed energy (8 MeV) to irradiate the chest wall, matched to a single megavoltage field (4 or 8 MV) irradiating the nodal areas in the axilla and supraclavicular fossa. (A separate parasternal field was not used.) All 500 cases treated in 1982 and 1983 with this method were reviewed (median follow-up 59 months). Four hundred and twenty-two were referred directly post-mastectomy and 78 for local recurrence after previous mastectomy. Of these, 42 were treated palliatively, and 458 with radical intent. In radical cases the given dose in both fields was 40 Gy in 15 fractions in 3 weeks. The overall survival (n = 458) was 51% (actuarial) at 5 years. At 5 years the local recurrence rate by site and UICC stage were as follows: chest wall - all Stages 17%, Stage I 4%, Stage II 13%, Stage III 26%, recurrent cases 21%; axillary recurrence - all Stages 20%, Stage I 4%, Stage II 10%, Stage III 22%, recurrent cases 39%; supraclavicular recurrences - all Stages 9%. Only one patient of the 500 treated had a parasternal recurrence. Late effects included mild telangiectasia in the electron field and asymptomatic apical lung fibrosis in the photon field. There was no match line fibrosis.

Adolescent↗
PubMed1991

Effects of carbon dioxide and sub-lethal levels of antibiotics on adherence of coagulase-negative staphylococci to polystyrene and silicone rubber.

Fifty coagulase-negative staphylococci (CNS) strains were investigated for adherence to both silicone rubber and polystyrene using a microtitre tray system. Culture in an atmosphere containing a physiological level of carbon dioxide (5% CO2) profoundly affected adherent growth to both surfaces. Most strains adhered less well in this atmosphere compared to in air alone, with mean reductions in adherence of 84% and 86% to silicone rubber and polystyrene respectively. Occasional strains adhered better in 5% CO2. The effects of antibiotic concentrations equivalent to 1/4 MIC of cefuroxime, ciprofloxacin, vancomycin and teicoplanin on the adherence of 10 CNS strains were also studied. Vancomycin and teicoplanin frequently increased adherence to silicone rubber and polystyrene compared to controls. The effects of antibiotics on adherence were not only strain dependent but also sometimes atmosphere or surface specific. Antibiotic-induced changes in adherence did not appear to correlate with changes in strain protein profiles or surface hydrophobicities.

Anti-Bacterial Agents↗
PubMed1991

Knowing someone with AIDS: the impact on adolescents.

Tested 25 adolescents who reported knowing a person with AIDS or HIV (PWA) and were matched by gender, race, grade, school type, and academic achievement with 25 adolescents who reported not knowing a PWA. The groups were compared with respect to their knowledge, beliefs, and social anxiety about AIDS and with respect to their worries about personal vulnerability to HIV infection. Social anxiety was significantly lower in those reporting knowing someone with AIDS than in the matching group. No significant differences between the two groups were found for knowledge, beliefs, or vulnerability worries. The implications of these findings for research on AIDS interventions with adolescents are discussed.

Achievement↗
PubMed1991

Variation in the expression of cell envelope proteins of coagulase-negative staphylococci cultured under iron-restricted conditions in human peritoneal dialysate.

Strains of coagulase-negative staphylococci (CNS), including Staphylococcus epidermidis, S. hominis, S. warnerii, S. simulans, S. capitis, S. haemolyticus and S. saprophyticus, were isolated from patients with continuous-ambulatory-peritoneal-dialysis-related peritonitis. The cell wall and cytoplasmic membrane protein profiles of CNS strains cultured in either nutrient broth (NB) or pooled human peritoneal dialysate (HPD) were compared. Some interspecies variation in both the wall and membrane protein profiles was noted. However, the cell wall protein profiles of HPD-grown CNS strains differed markedly from those cultured in NB. Growth in HPD resulted in a marked reduction in the total number of cell-wall-associated proteins but up to three antigenically related proteins in the 40-56 kDa range, depending on the species, predominated. Growth in HPD also resulted in the induction of two iron-repressible cytoplasmic membrane proteins (IRMPs) of 32 and 36 kDa in S. epidermidis. Other CNS strains only appeared to express a single IRMP, which varied in molecular mass from 32 to 36 kDa. Whilst the IRMP in these CNS strains showed considerable antigenic homology with the 32 kDa IRMP, the S. warneri IRMP showed cross-reactivity with both the 32 and 36 kDa IRMPs of S. epidermidis. Immunoblotting experiments revealed that whilst the CNS cell wall proteins were poorly immunogenic, the IRMPs were the immunodominant CNS protein antigens, reacting strongly with antibodies present in HPD. This finding provides evidence to suggest that the IRMPs are expressed in vivo during infection.

Antibodies, Bacterial↗
PubMed1991

Characterization of cell envelope proteins of Staphylococcus epidermidis cultured in human peritoneal dialysate.

The cell envelope protein profiles of Staphylococcus epidermidis cultured in used human peritoneal dialysate (HPD) differed markedly from those of cells cultured in nutrient broth. Compared with broth-grown cells, many cell wall proteins were repressed in HPD, although three proteins of 42, 48, and 54 kDa predominated and an iron-repressible 130-kDa protein was induced. Growth in HPD also resulted in expression of two cell membrane proteins of 32 and 36 kDa which were iron repressible. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analysis using monospecific polyclonal antisera raised against the 32- and 36-kDa proteins revealed considerable antigenic and molecular mass homology among 12 S. epidermidis isolates from patients with continuous ambulatory peritoneal dialysis-related peritonitis. The 32-kDa antiserum also cross-reacted with a 32-kDa S. aureus cell membrane protein. Immunoblots of S. epidermidis cell walls and membranes were also probed with normal human serum and serum and HPD from continuous ambulatory peritoneal dialysis patients. While the cell wall proteins of S. epidermidis appeared to be relatively poorly immunogenic, the 32- and 36-kDa membrane proteins reacted strongly with antibodies present in each of the body fluids evaluated. These results suggest that the highly conserved 32- and 36-kDa iron-repressible proteins are expressed during growth in vivo and may be involved in iron transport, since all 12 S. epidermidis strains examined also produced iron chelators.

Bacterial Proteins↗
PubMed1991

Surface exposure of O1 serotype lipopolysaccharide in Klebsiella pneumoniae strains expressing different K antigens.

Surface exposure of the O1 serotype lipopolysaccharide in encapsulated Klebsiella pneumoniae strains belonging to different serotypes was examined by using the O1 antigen-specific bacteriophages FC3-1 and FC3-2 in conjunction with immunogold electron microscopy and enzyme immunoassays with specific antisera. Despite the presence of the capsular polysaccharide, the O1 antigen was exposed at the cell surface in strains producing K2, K7, K8, K12, K19, K21, K22, K34, K35, K42, K45, K55, K57, K62, K66, K69, and K70 capsular polysaccharides. However, in strains producing K1, K10, and K16 capsular polysaccharides, the O1 antigen was masked by the K antigen. These results suggest that, since the O1 antigen is surface exposed in many different strains of K. pneumoniae with different capsular serotypes and is also able to immunoprotect, its potential as a useful vaccine component should not be overlooked.

Animals↗
PubMed1991

AGP/EBP(LAP) expressed in rat hepatoma cells interacts with multiple promoter sites and is necessary for maximal glucocorticoid induction of the rat alpha-1 acid glycoprotein gene.

Transcription of the rat alpha 1-acid glycoprotein (AGP) gene is induced by glucocorticoids. In addition to the glucocorticoid response element which maps to bases -120 to -107, sequences located between bases -106 to -42 have been shown to be necessary for hormone induction. We have previously identified multiple sites of C/EBP interaction with the AGP promoter in the region -106 to -64. In this study, we purify and identify a C/EBP family member, AGP/EBP(LAP), present in the rat hepatoma cell line HTC (JZ.1) which also binds to the C/EBP recognition sites in this region. Mutations in the recognition sites that prevent binding are analyzed, and the results suggest a positive as well as a possible inhibitory role for AGP/EBP(LAP) in the glucocorticoid induction of the gene in HTC (JZ.1) cells.

Animals↗
PubMed1991

A safety adaptation to Interlandi headgear.

Extra-oral traction (E.O.T.) to a facebow is used with many types of removable, functional, and fixed orthodontic appliances. A versatile and popular method involves the elastic force being provided by an Interlandi headgear. The facebow, which is of necessity removable, can be displaced from its intra-oral attachments (whilst still connected to the headgear by the elastics) and may result in personal injury. This paper describes a suitable simply made device that can be incorporated to prevent facebow dislodgement, thereby improving safety.

Accident Prevention↗
PubMed1991

Penetration of administered IgG into the maxillary sinus and long-term clinical effects of intravenous immunoglobulin replacement therapy on sinusitis in primary hypogammaglobulinaemia.

The influence of long-term intravenous immunoglobulin (i.v. IgG) replacement therapy on the clinical course of chronic sinusitis in patients with primary hypogammaglobulinaemia has not previously been reported. We have analysed the efficacy of i.v. IgG therapy and the penetration of administered i.v. IgG into the maxillary sinus. Seventeen patients with primary hypogammaglobulinaemia received i.v. IgG replacement therapy to maintain pre-infusion serum IgG concentrations above 4 g/l for periods of 12 to 58 (mean 36.7) months. Cases with established chronic sinusitis prior to therapy did not have symptomatic or radiological improvement at this dose, although no sinusitis developed de-novo in the 3 previously unaffected patients. The administered IgG penetrated into maxillary sinus antral lavage fluid in 3 patients from whom secretions were obtained at antroscopy. This indicates that poor clinical responses are not due to lack of penetration of antibodies to the required sites of action. Larger doses of i.v. IgG may be more effective in this situation, but the addition of antibiotics at high dosage may be a more economical therapeutic alternative. These findings highlight the importance of diagnosis of hypogammaglobulinaemia by measurement of serum IgG concentrations in patients who suffer from recurrent sinusitis, as the early institution of i.v. IgG therapy may prevent the development of sinusitis refractory to i.v. IgG therapy.

Adolescent↗
PubMed1991

Hypotensive properties of the protein kinase inhibitor, staurosporine, in normotensive and spontaneously hypertensive rats.

The protein kinase inhibitor, staurosporine, was examined for hemodynamic actions in conscious rats and for its effects on isolated vascular smooth muscle. In conscious normotensive rats, staurosporine, 0.1 to 1.0 mg/kg intravenous, produced a dose-related decrease in blood pressure. Doses of 0.1 and 0.5 mg/kg produced reflex tachycardia, while heart rate decreased following 1.0 mg/kg. Higher doses of staurosporine (5 and 10 mg/kg), although not significantly altering heart rate, caused a precipitous drop in blood pressure and all rats died within 48 hours of treatment. Spontaneously hypertensive rats were significantly more sensitive than normotensive rats to the blood pressure lowering effects of staurosporine. The depressor activity of staurosporine was also observed in cord-stimulated pithed rats indicating that hypotension is a peripherally- rather than centrally-mediated effect of staurosporine. In ring preparations of rat thoracic aorta, staurosporine (3 nM to 0.1 mM) produced a concentration-dependent inhibition of serotonin-induced contraction, consistent with its ability to lower blood pressure by an effect at a peripheral vascular site. These results provide the first documentation of the potent cardiovascular activity of staurosporine in the conscious rat and support the contention that protein kinases, in particular protein kinase C, may be important in the regulation of vascular tone.

Alkaloids↗