Search PubMed⌕ Search

Biomedical subjects

D J White

Publications and source records attributed to D J White.

At least 19 recordsLinked to original sources
PubMed2006

A method to study sustained antimicrobial activity of rinse and dentifrice components on biofilm viability in vivo.

AIM: To develop an improved method for quantitative assessment of antimicrobial efficacy and substantivity of mouth rinses and dentifrices on in vivo treated plaque. MATERIAL AND METHODS: Nine- and 72-h-old plaques were formed in volunteers carrying out standardized hygiene using NaF-containing dentifrice. Plaques were collected before (baseline) in vivo treatment with dentifrices or chlorhexidine mouth rinse, immediately post-treatment and after 1 or 6 h, dispersed in demineralized water and stained with live/dead stain after which bacteria were enumerated. Dispersed baseline plaques were treated with dentifrices or chlorhexidine to determine antimicrobial efficacy against planktonic bacteria. RESULTS: Baseline plaques revealed 56-41% viable organisms in 9- and 72-h-old plaques, respectively. Treatment of planktonic (dispersed baseline plaque) bacteria resulted in 1-4% viable organisms. Chlorhexidine mouth rinse and dentifrices produced strong immediate antimicrobial effects, but after 1 or 6 h, the proportion of viable organisms in 9-h-old plaques rebounded significantly with only chlorhexidine mouth rinse retaining significant efficacy. Seventy-two-hour-old plaques were less susceptible to antimicrobials, although dentifrices appeared more effective after 6 h than initially, whereas efficacy of chlorhexidine rinse continued to drop with time post-treatment. CONCLUSIONS: The proposed method holds promise for assessment of both immediate and retained antimicrobial actions of oral treatments against dental plaque in vivo.

Anti-Infective Agents, Local↗
PubMed2004

Zafirlukast for severe recurrent vulvovaginal candidiasis: an open label pilot study.

BACKGROUND: Recurrent vulvovaginal candidiasis (VVC) has been linked to allergic disease, particularly allergic rhinitis. OBJECTIVE: A pilot study to assess the possible use of the leukotriene receptor antagonist zafirlukast as a treatment for recurrent VVC. METHODS: 20 women with six or more symptomatic attacks of VVC in the past year (at least four proved microbiologically). Clinical atopy determined by the International Study for Asthma and Allergies in Childhood (ISAAC) questionnaire assessed blindly. Monitoring by daily symptom diary and self taken vaginal swabs. Treatment with zafirlukast 20 mg twice daily for 24 weeks or until three microbiologically confirmed episodes of VVC. Response assessed by daily symptom diary and self taken vaginal swabs. Subjective response scales for improvement, side effects, and change in other allergic disease completed when stopping treatment. Semistructured telephone interview 1 year after stopping medication. RESULTS: 14 patients (70%) reported a subjective response on the improvement response scale. Six (30%) showed a complete response with no further symptomatic attacks of VVC or negative swabs when symptomatic. Seven (37%) remained symptom free 18 months after entering the study-that is, 12 months after stopping therapy. 11 (58%) remained symptom free for at least 3 months after stopping therapy. This does not include one patient who remained symptom free but continued on zafirlukast because of an improvement in her asthma. There was no clear relation between response and atopic status. Six of nine atopic subjective responders reported improvements in other allergic symptoms. Side effects were minimal; one seemed clearly attributable to the drug. CONCLUSION: Zafirlukast offers a potential new treatment for recurrent VVC that requires confirmation in controlled studies.

Adult↗
PubMed2004

Surveillance of sexually transmitted infections in the West Midlands using anonymised individual patient datasets from genitourinary medicine clinics.

Sexually transmitted infections (STIs) declined in the UK during the 1980s and early 1990s but have increased substantially since 1995. Within the overall increase there are important differences in the epidemiology of these infections. The current, aggregate system of STI data collection in the UK provides limited demographic information and is unable to fully explain these differences. More useful information can be obtained using an enhanced surveillance system that collects disaggregate, anonymised, individual patient data including ethnic group and truncated postcode of residence. Such a system has been set up in the West Midlands NHS region. The methodology of the project is described here along with the findings to date. These findings confirm that the burden of STIs disproportionately affects young persons, men who have sex with men, black ethnic minority groups and those living in urban areas. Identifying the groups at greatest risk in this way enables interventions to be more usefully targeted.

Adolescent↗
PubMed2003

The influence of a hexametaphosphate-containing chewing gum on the wetting ability of salivary conditioning films in vitro and in vivo.

OBJECTIVE: Adsorbed conditioning films of salivary components on dental enamel surfaces or pellicles form the interface between teeth and the oral environment. The wetting ability of salivary conditioning films dictates biological adhesion phenomena such as plaque formation, calcification and staining, and also influences mouth perception through effects on lubricity. This study assessed the effects of hexametaphosphate release from a chewing gum matrix on the wetting ability of salivary conditioning films in vitro and in vivo. METHODOLOGY: Results obtained for hexametaphosphate chewing gum were compared with those produced by hexametaphosphate-containing dentifrice, which has been clinically proven to have efficacy for stain removal and prevention and dental calculus prevention. RESULTS: Contact angle assessments revealed that hexametaphosphate dentifrice produced markedly hydrophilic conditioning films in vitro. Hexametaphosphate chewing gums had only minor effects on surface contact angles in vitro. However, in vivo intra-oral contact angle measurements on tooth surfaces in volunteers showed that both hexametaphosphate dentifrice and chewing gum produced more hydrophilic tooth surfaces. CONCLUSION: These results support the activity of hexametaphosphate on tooth surfaces delivered both from dentifrice and chewing gum forms.

Adhesiveness↗
PubMed2002

Genetic aberrations detected by comparative genomic hybridisation in vulvar cancers.

Squamous cell carcinoma of the vulva is a disease of significant clinical importance, which arises in the presence or absence of human papillomavirus. We used comparative genomic hybridisation to document non-random chromosomal gains and losses within human papillomavirus positive and negative vulvar cancers. Gain of 3q was significantly more common in human papillomavirus-positive cancers compared to human papillomavirus-negative cancers. The smallest area of gain was 3q22-25, a chromosome region which is frequently gained in other human papillomavirus-related cancers. Chromosome 8q was more commonly gained in human papillomavirus-negative compared to human papillomavirus-positive cancers. 8q21 was the smallest region of gain, which has been identified in other, non-human papillomavirus-related cancers. Chromosome arms 3p and 11q were lost in both categories of vulvar cancer. This study has demonstrated chromosome locations important in the development of vulvar squamous cell carcinoma. Additionally, taken together with previous studies of human papillomavirus-positive cancers of other anogenital sites, the data indicate that one or more oncogenes important in the development and progression of human papillomavirus-induced carcinomas are located on 3q. The different genetic changes seen in human papillomavirus-positive and negative vulvar squamous cell carcinomas support the clinicopathological data indicating that these are different cancer types.

Carcinoma, Squamous Cell↗
PubMed2002

Influence of dentifrices and dietary components in saliva on wettability of pellicle-coated enamel in vitro and in vivo.

In vitro salivary pellicles were found to be less hydrophobic by water contact angles than clinically formed pellicles. In this study, water contact angles were measured on enamel coated with pellicles adsorbed from reconstituted human whole saliva (RHWS) and after exposure to dentifrices or dietary components. In addition, adhesion of Streptococcus oralis J22 to pellicles formed from RHWS with minor amounts of milk added and after exposure to dentifrices was studied. Exposure of RHWS-pellicles to milk or salad oil yielded an increase in the hydrophobicity of in vitro pellicles to values observed in vivo, but a decrease was seen after exposure to a sugar solution. Pellicles formed from saliva with 0.4% milk added attracted less S. oralis cells than pellicles formed in the absence of milk components. Exposure of pellicles formed from saliva with milk added to various dentifrices had a variable effect on bacterial adhesion: markedly lower numbers of adhering S. oralis were found for a dentifrice with NaF, but exposure to dentifrices containing SnF2 or hexametaphosphate showed slightly increased adhesion. In summary, dietary components have influence on the hydrophobicity of enamel pellicles, while combinations of dietary components and dentifrices certainly influence the adhesiveness of the pellicles. The effects of dietary components on pellicle conditioning film should be taken into consideration in research on the development of ingredients to control intraoral surface chemistry and microbiology, as well as in the development of oral products.

Animals↗
PubMed2001

Penetration of efavirenz into the male genital tract: drug concentrations and antiviral activity in semen and blood of HIV-1-infected men.

Efavirenz is a potent non-nucleoside reverse transcriptase inhibitor, licensed for the treatment of HIV-1. Data on sanctuary site penetration are limited. Therefore, we measured efavirenz concentrations in the blood and semen of 19 HIV-1-positive men and found concentrations in seminal plasma averaged 10% of those in blood plasma. Furthermore, seminal plasma viral loads were suppressed by 24 weeks of therapy in all patients. These data suggest that efavirenz-containing regimens have antiviral activity within the male genital tract.

Alkynes↗
PubMed2001

Identification of the high affinity Mn2+ binding site of bacteriophage lambda phosphoprotein phosphatase: effects of metal ligand mutations on electron paramagnetic resonance spectra and phosphatase activities.

Bacteriophage lambda phosphoprotein phosphatase (lambdaPP) has structural similarity to the mammalian Ser/Thr phosphoprotein phosphatases (PPPs) including the immunosuppressant drug target calcineurin. PPPs possess a conserved active site containing a dinuclear metal cluster, with metal ligands provided by a phosphoesterase motif plus two additional histidine residues at the C-terminus. Multiple sequence alignment of lambdaPP with 28 eubacterial and archeal phosphoesterases identified active site residues from the phosphoesterase motif and in many cases 2 additional C-terminal His metal ligands. Most highly similar to lambdaPP are E. coli PrpA and PrpB. Using the crystal structure of lambdaPP [Voegtli, W. C., et al. (2000) Biochemistry 39, 15365-15374] as a structural and active site model for PPPs and related bacterial phosphoesterases, we have studied mutant forms of lambdaPP reconstituted with Mn(2+) by electron paramagnetic resonance (EPR) spectroscopy, Mn(2+) binding analysis, and phosphatase kinetics. Analysis of Mn(2+)-bound active site mutant lambdaPP proteins shows that H22N, N75H, and H186N mutations decrease phosphatase activity but still allow mononuclear Mn(2+) and [(Mn(2+))(2)] binding. The high affinity Mn(2+) binding site is shown to consist of M2 site ligands H186 and Asn75, but not H22 from the M1 site which is ascribed as the lower affinity site.

Amino Acid Sequence↗
PubMed2001

Expression of complement regulatory proteins on islets of Langerhans: a comparison between human islets and islets isolated from normal and hDAF transgenic pigs.

BACKGROUND: The expression of regulators of complement activity (RCAs) on islet cells may be of great importance for protecting them against complement-mediated lysis in the immediate posttransplant period after intraportal islet transplantation. We examined porcine and human islet cells for expression of RCA. We also examined to what extent human decay accelerating factor (hDAF) is expressed on adult and fetal islet cells isolated from hDAF transgenic (TG) pigs having a high transgene expression on endothelial cells. Moreover, the susceptibility of the various types of cells to lysis in human serum and blood was investigated. METHODS: Adult human islets (n=5), normal adult and fetal porcine islets (n=9 and n=8, respectively), and islets from adult and fetal hDAF TG pigs (n=5 and n=6, respectively) were examined. With islet single-cell suspensions and flow cytometry, adult human islet cells were examined for expression of hDAF (CD55), hCD59, and human membrane cofactor protein (hMCP; CD46), while porcine islet cells were examined for expression of pCD59 and pMCP. Islet cells from hDAF TG pigs were also examined for hDAF expression. Porcine peripheral blood lymphocytes, normal and hDAF TG porcine endothelial cell lines, a human endothelial cell line, and the human cell line U937 served as controls. Islet cytotoxicity was assayed after incubation of the islet cells with fresh human serum. Furthermore, adult islets from normal control pigs and hDAF TG pigs were exposed to fresh human blood in vitro for 60 min, and the inflammatory reaction elicited was compared between the different types of islets. RESULTS: All human islet cell preparations expressed hCD59, two of five expressed hMCP, but none expressed hDAF. Porcine islet cells expressed both pCD59 and pMCP. Normal adult porcine islet cells exposed to fresh human serum resulted in 74+/-5.4% cell lysis (mean+/-SEM, n=16). In comparison, only 1.3+/-2.8% (n=20, P<0.001) of human islet cells were lysed in the human serum. One islet cell preparation from an hDAF TG pig expressed small amounts of hDAF. This preparation from hDAF TG pigs bound significantly less C3c than did normal control islets (mean fluorescence ratio 16+/-2.2 and 58+/-4.3, respectively; P=0.046) and were partially protected from cell lysis in fresh human serum (47+/-10% and 78+/-18% cell lysis, respectively; P=0.046). The other four preparations from hDAF TG pigs were negative for hDAF and were equally susceptible to lysis as normal control islets. All fetal pancreatic islet cells from hDAF TG pigs analyzed were negative for hDAF expression. When exposed to fresh human blood in vitro, adult and fetal islets from hDAF TG pigs elicited equally strong inflammatory changes as did the normal control islets. The inflammatory changes were characterized by activation of the complement and coagulation systems, resulting in islet damage with "dumping" of insulin into the blood. CONCLUSIONS: Porcine and human islet cells express species-restricted complement regulatory proteins, with the human islet cells expressing mainly hCD59. A low expression of hDAF was detected on islet cells from one of five hDAF TG pigs. These islet cells displayed reduced islet cell cytotoxicity in fresh human serum. We conclude that protection from complement-mediated lysis will be important in the context of intraportal pig-to-human islet transplantation, and expression of a human RCA on islet cells should be beneficial in this context.

Animals↗
PubMed2001

Two crystal structures of the cytoplasmic molybdate-binding protein ModG suggest a novel cooperative binding mechanism and provide insights into ligand-binding specificity.

The X-ray structures of the cytoplasmic molybdate-binding protein ModG from Azotobacter vinelandii in two different crystal forms have been determined. For such a small protein it is remarkably complex. Each 14.3 kDa subunit contains two small beta-barrel domains, which display an OB-fold motif, also seen in the related structure of ModE, a molybdenum-dependent transcriptional regulator, and very recently in the Mop protein that, like ModG, has been implicated in molybdenum homeostasis within the cell. In contrast to earlier speculation, the functional unit of ModG is actually not a dimer (as in ModE), but a trimer capable of binding a total of eight molybdate molecules that are distributed between two disparate types of site. All the binding sites are located at subunit interfaces, with one type lying on a crystallographic 3-fold axis, whilst the other lies between pairs of subunits. The two types of site are linked by short hydrogen bond networks that may suggest a cooperative binding mechanism. A superposition of two subunits of the ModG trimer on the apo-ModE dimer allows the probable locations of the molybdate-binding sites of the latter to be assigned. Through structural comparisons with other oxyanion-binding proteins, including Mop and ModE, it is possible to speculate about ligand-binding affinities, selectivity and evolution.

Aldehyde Oxidoreductases↗
PubMed2001

GidA is an FAD-binding protein involved in development of Myxococcus xanthus.

A gene encoding a homologue of the Escherichia coli GidA protein (glucose-inhibited division protein A) lies immediately upstream of aglU, a gene encoding a WD-repeat protein required for motility and development in Myxococcus xanthus. The GidA protein of M. xanthus shares about 48% identity overall with the small (approximately equal to 450 amino acid) form of GidA from eubacteria and about 24% identity overall with the large (approximately equal to 620 amino acid) form of GidA from eubacteria and eukaryotes. Each of these proteins has a conserved dinucleotide-binding motif at the N-terminus. To determine if GidA binds dinucleotide, the M. xanthus gene was expressed with a His6 tag in E. coli cells. Purified rGidA is a yellow protein that absorbs maximally at 374 and 450 nm, consistent with FAD or FMN. Thin-layer chromatography (TLC) showed that rGidA contains an FAD cofactor. Fractionation and immunocytochemical localization show that full length GidA protein is present in the cytoplasm and transported to the periplasm of vegetative-grown M. xanthus cells. In cells that have been starved for nutrients, GidA is found in the cytoplasm. Although GidA lacks an obvious signal sequence, it contains a twin arginine transport (Tat) motif, which is conserved among proteins that bind cofactors in the cytoplasm and are transported to the periplasm as folded proteins. To determine if GidA, like AglU, is involved in motility and development, the gidA gene was disrupted. The gidA- mutant has wild-type gliding motility and initially is able to form fruiting bodies like the wild type when starved for nutrients. However, after several generations, a stable derivative arises, gidA*, which is indistinguishable from the gidA- parent on vegetative medium, but is no longer able to form fruiting bodies. The gidA* mutant releases a heat-stable, protease-resistant, small molecular weight molecule that acts in trans to inhibit aggregation and gene expression of wild-type cells during development.

Amino Acid Sequence↗
PubMed2001

Physiological aspects of pig-to-primate renal xenotransplantation.

BACKGROUND: Few data exist on the physiological aspects of pig-to-primate renal xenotransplantation. METHODS: Use of organs transgenic for human decay accelerating factor has allowed assessment of the metabolic and hormonal functions of these xenografts. RESULTS: Porcine renal xenografts largely maintain plasma electrolyte homeostasis. An increase in proteinuria was detected that may result from graft injury. In contrast to allotransplantation a severe anaemia developed requiring recipient treatment with exogenous human erythropoietin. CONCLUSIONS: Our experience provides qualified encouragement for the likely physiological compatibility of pig and primate species, but identifies areas where a xenograft may not match the performance of an allograft.

Anemia↗
PubMed2001

Antiretroviral drug concentrations in semen of HIV-infected men: differential penetration of indinavir, ritonavir and saquinavir.

Variable drug penetration of antiretroviral drugs into the genital tract may contribute to the differential evolution of HIV and the emergence of drug resistance. This, in turn, may have an impact on the sexual transmission of resistant HIV in patients treated with antiretroviral drugs. We have measured concentrations of the HIV-1 protease inhibitors indinavir, ritonavir and saquinavir in the blood plasma (BP) and seminal plasma (SP) of 23 HIV-1-positive men. Forty-five time-matched blood and semen samples were obtained. SP concentrations of indinavir exceeded the EC95 of indinavir, corrected for protein binding, of 42 ng/mL at all time intervals. In contrast, the median ritonavir and saquinavir SP concentrations were below the relevant EC95 at all times post drug ingestion. The median SP:BP concentration ratios for indinavir were 0.6, 0.8 and 1.4, respectively, at 0-2, 2-6 and 6-8 h post-drug ingestion. In contrast, the median SP:BP concentration ratios at 0-3, 3-9 and 9-12 h post-drug ingestion were <0.02, <0.04 and <0.04, respectively, for both ritonavir and saquinavir. These differences justify further study of HIV-1 evolution and development of resistance in the genital tract of men taking these anti-HIV drugs.

Adult↗
PubMed2001

Antioxidant vitamin therapy alters burn trauma-mediated cardiac NF-kappaB activation and cardiomyocyte cytokine secretion.

BACKGROUND: This study examined the effects of antioxidant vitamins A, C, and E on nuclear transcription factor-kappa B (NF-kappaB) nuclear translocation, on secretion of inflammatory cytokines by cardiac myocytes, and on cardiac function after major burn trauma. METHODS: Adult rats were divided into four experimental groups: group I, shams; group II, shams given oral antioxidant vitamins (vitamin C, 38 mg/kg; vitamin E, 27 U/kg; vitamin A, 41 U/kg 24 hours before and immediately after burn); group III, burns (third-degree scald burn over 40% total body surface area) given lactated Ringer's solution (4 mL/kg/% burn); and group IV, burns given lactated Ringer's solution plus vitamins as described above. Hearts were collected 4, 8, 12, and 24 hours after burn to assay for NF-kappaB nuclear translocation, and hearts collected 24 hours after burn were examined for cardiac contractile function or tumor necrosis factor-alpha secretion by cardiomyocytes. RESULTS: Compared with shams, left ventricular pressure was lower in burns given lactated Ringer's solution (group III) (88 +/- 3 vs. 64 +/- 5 mm Hg, p < 0.01) as was +dP/dt max (2,190 +/- 30 vs. 1,321 +/- 122 mm Hg/s) and -dP/dt max (1,775 +/- 71 vs. 999 +/- 96 mm Hg, p < 0.01). Burn injury in the absence of vitamin therapy (group III) produced cardiac NF-kappaB nuclear migration 4 hours after burn and cardiomyocyte secretion of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 by 24 hours after burn. Antioxidant therapy in burns (group IV) improved cardiac function, producing left ventricular pressure and +/-dP/dt (82 +/- 2 mm Hg, 1,880 +/- 44 mm Hg, and 1,570 +/- 46 mm Hg/s) comparable to those measured in shams. Antioxidant vitamins in burns inhibited NF-kappaB nuclear migration at all times after burn and reduced burn-mediated cytokine secretion by cardiomyocytes. CONCLUSION: These data suggest that antioxidant vitamin therapy in burn trauma provides cardioprotection, at least in part, by inhibiting translocation of the transcription factor NF-kappaB and interrupting cardiac inflammatory cytokine secretion.

Animals↗
PubMed2001

West Nile virus: a case study in how NY State Health Information infrastructure facilitates preparation and response to disease outbreaks.

New York's (NY) Health Information Network (HIN) provided timely access to West Nile Virus (WNV) data during the initial outbreak in the late Summer 1999. In December 1999, NY developed a plan to deal with WNV in 2000 that required an integrated surveillance system for humans, birds, mammals, and mosquitoes. The HIN infrastructure allowed NY to deploy this system statewide in three months. Local health departments throughout NY used the system to report, track, and retrieve surveillance data as WNV spread throughout NY in 2000. The HIN infrastructure includes partnerships, training/support, technical capacity and architecture similar to NEDSS as proposed by the US CDC.

Animals↗