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Biomedical subjects

D J White

Publications and source records attributed to D J White.

At least 37 records · Page 2Linked to original sources
PubMed2001

Vector surveillance for West Nile virus.

West Nile virus (WNV) was detected in the metropolitan New York City (NYC) area during the summer and fall of 1999. Sixty-two human cases, including seven fatalities, were documented. The New York State Department of Health (NYSDOH) initiated and implemented a statewide mosquito and WNV surveillance system. We developed a WNV response plan designed to provide local health departments (LHD) a standardized means to begin to assess basic mosquito population data and to detect WNV circulation in mosquito populations. During the 2000 arbovirus surveillance season, local health agencies collected 317,676 mosquitoes and submitted 9,952 pools for virus testing. NYSDOH polymerase chain reaction (PCR) testing detected 363 WNV-positive pools. Eight species of mosquitoes were found to be infected. Of the 26 counties conducting mosquito surveillance, WNV-positive mosquitoes were detected only in NYC, on Long Island, and in four counties in the lower Hudson River valley region. LHD larval surveillance provided initial or enhanced mosquito habitat location and characterization and mosquito species documentation. Adult mosquito surveillance provided LHD information on species' presence, density, seasonal fluctuations, virus infection, minimum infection ratios (MIR) and indirect data on mosquito control efficacy after larval or adult control interventions. Collective surveillance activities conducted during 1999 and 2000 suggest that WNV has dispersed throughout the state and may affect local health jurisdictions within NYS, adjacent states, and Canada in future years. Vector surveillance will remain a critical component of LHD programs addressing public health concerns related to WNV.

Animals↗
PubMed2001

Combined topical flucytosine and amphotericin B for refractory vaginal Candida glabrata infections.

Patients with vaginitis due to highly azole resistant Candida glabrata can be particularly difficult to treat. We describe three cases of longstanding vaginal candidiasis due to C glabrata. These had failed to respond to local and systemic antifungals. Flucytosine (1 g) and amphotericin B (100 mg) formulated in lubricating jelly base in a total 8 g delivered dose, was used per vagina once daily for 14 days with significant improvement, both clinically and microbiologically.

Adult↗
PubMed2001

Overexpression of cardiac I-kappaBalpha prevents endotoxin-induced myocardial dysfunction.

Nuclear factor-kappa B (NF-kappaB) is an inducible transcription factor that regulates expression of many genes, such as tumor necrosis factor-alpha (TNF-alpha), which may contribute to myocardial dysfunction. We investigated whether cardiac NF-kappaB activation is involved in the development of myocardial dysfunction after lipopolysaccharide (LPS) challenge. Mice were intraperitoneally injected with LPS, and the hearts were harvested and assayed for NF-kappaB translocation. After LPS challenge, NF-kappaB activation was detected within 30 min and remained for 8 h. In transgenic mice constitutively overexpressing a nondegradable form of I-kappaBalpha (I-kappaBalphaDeltaN) in cardiomyocytes, myocardial NF-kappaB translocation was prevented after LPS challenge. Myocytes isolated from these transgenics secreted significantly less TNF-alpha than did wild-type cardiomyocytes after LPS stimulation. When whole hearts were excised, perfused in a Langendorff preparation, and challenged with endotoxin, I-kappaBalphaDeltaN transgenic hearts displayed normal cardiac function, whereas profound contractile dysfunction was observed in wild-type hearts. These data indicate that myocardial NF-kappaB translocates within minutes after LPS administration. Inhibition of myocyte NF-kappaB activation by overexpression of myocyte I-kappaBalpha is sufficient to block cardiac TNF-alpha production and prevent cardiac dysfunction after LPS challenge.

Animals↗
PubMed2001

Targeted disruption of ICAM-1, P-selectin genes improves cardiac function and survival in TNF-alpha transgenic mice.

We have developed a transgenic mouse model in which tumor necrosis factor (TNF)-alpha is overexpressed exclusively in the heart under the regulation of the alpha-myosin heavy chain promoter. These animals develop chronic heart failure associated with severe leukocyte infiltration in both the atria and the ventricles. The purpose of this study was to investigate the role of adhesion molecules in mediating cardiac dysfunction in the TNF-alpha transgenic model. TNF-alpha transgenic mice were bred with mice null for intercellular adhesion molecule (ICAM)-1 and P-selectin genes to obtain a lineage of ICAM-1 and P-selectin null mice with selective overexpression of TNF-alpha in the heart. TNF-alpha transgenic animals showed marked upregulation of ICAM-1 mRNA and protein; however, P-selectin mRNA and protein remained undetectable despite chronic TNF overexpression. Cardiac function was markedly improved in the ICAM-1(-/-), P-selectin(-/-), TNF-alpha transgenic group versus the ICAM(+/+), P-selectin(+/+), TNF-alpha transgenic group. Kaplan-Meier survival curves showed statistically significant prolonged survival in the ICAM-1(-/-), P-selectin(-/-), TNF-alpha transgenic animals. These data suggest that ICAM-1 mediates at least in part the cardiac dysfunction induced by TNF-alpha expression by cardiac myocytes.

Animals↗
PubMed2001

Role of p38 mitogen-activated protein kinase in cardiac myocyte secretion of the inflammatory cytokine TNF-alpha.

This study examined the hypothesis that burn trauma promotes cardiac myocyte secretion of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and produces cardiac contractile dysfunction via the p38 mitogen-activated protein kinase (MAPK) pathway. Sprague-Dawley rats were divided into four groups: 1) sham burn rats given anesthesia alone, 2) sham burn rats given the p38 MAPK inhibitor SB203580 (6 mg/kg po, 15 min; 6- and 22-h postburn), 3) rats given third-degree burns over 40% total body surface area and treated with vehicle (1 ml of saline) plus lactated Ringer solution for resuscitation (4 ml x kg(-1). percent burn(-1)), and 4) burn rats given injury and fluid resuscitation plus SB203580. Rats from each group were killed at several times postburn to examine p38 MAPK activity (by Western blot analysis or in vitro kinase assay); myocardial function and myocyte secretion of TNF-alpha were examined at 24-h postburn. These studies showed significant activation of p38 MAPK at 1-, 2-, and 4-h postburn compared with time-matched shams. Burn trauma impaired cardiac mechanical performance and promoted myocyte secretion of TNF-alpha. SB203580 inhibited p38 MAPK activity, reduced myocyte secretion of TNF-alpha, and prevented burn-mediated cardiac deficits. These data suggest p38 MAPK activation is one aspect of the signaling cascade that culminates in postburn secretion of TNF-alpha and contributes to postburn cardiac dysfunction.

Animals↗
PubMed2001

Lyme disease in New York State: spatial pattern at a regional scale.

Lyme disease occurs commonly in New York State, but its geographic distribution is heterogeneous. Over each of nine consecutive years, incidence rates from 57 New York State counties were subjected to spatial autocorrelation analysis. Although the epidemic advanced during the study period, the analyses reveal a consistent pattern of spatial dependence. The correlation distance, the distance over which incidence rates covary positively, remained near 120 km over the nine years. A local spatial analysis around Westchester County, a major disease focus, indicated that the global correlation distance matched the extent of the most intense local clustering; statistically weaker clustering extended to 200 km from Westchester. Analyzing the spatial character of the epidemic may reveal the epizootic processes underlying patterns in human infection, and may help identify a spatial scale for regional control of disease.

Humans↗
PubMed2001

Anticaries profile qualification of an improved whitening dentifrice.

A series of pH cycling "profile" laboratory studies was conducted to confirm the anticaries potential of an enhanced cleaning and whitening dentifrice based on a novel abrasive polishing silica and pyrophosphate tartar control source, with sodium fluoride as the anticaries ingredient. Under pH cycling remineralization conditions, the whitening dentifrice produced lesion fluoridation comparable to a conventional tartar control dentifrice containing combinations of pyrophosphate anion and a NaF fluoride ion source. Under pH cycling lesion progression conditions, the whitening dentifrice produced enamel protection against caries development, comparable to control dentifrices containing NaF alone or in combination with tartar control pyrophosphate anion. These results are consistent with clinical data supporting the effectiveness of NaF dentifrices combined with anionic tartar control inhibitors such as pyrophosphate. These results support the anticaries effectiveness of the enhanced cleaning and whitening dentifrice based upon "Stain-Specific Soft Silica."

Analysis of Variance↗
PubMed2001

Laboratory stain removal and abrasion characteristics of a dentifrice based upon a novel silica technology.

These laboratory studies examined the stain removal efficacy and hard tissue abrasivity of a new dentifrice formulation--Crest Extra Whitening--based on the incorporation of elevated concentrations of a proprietary silica. Cleaning power assessments were made using a modification of the laboratory test method developed by Stookey and associates at Indiana University Oral Health Research Institute. Abrasion assessments were made using Radioactive Enamel and Radioactive Dentin Abrasivity (REA and RDA) measures. Results show that Crest Extra Whitening dentifrice produced statistically significantly improved stain removal when compared to a number of conventional dentifrices, including Crest Cavity Protection and Crest Tartar Protection, and a number of recently marketed cleaning and whitening dentifrices. Laboratory studies further demonstrated that the Crest Extra Whitening dentifrice produces dentin and enamel abrasivity similar to conventional silica dentifrices.

Aluminum Oxide↗
PubMed2001

In vitro studies of the anticalculus efficacy of an improved whitening dentifrice.

Crystal growth inhibition and plaque biofilm calcification laboratory studies were conducted to confirm the anticalculus potential of an enhanced cleaning and whitening dentifrice, based upon a novel enamel-safe, abrasive-polishing silica and pyrophosphate tartar control source with sodium fluoride as the anticaries ingredient. Calcium hydroxyapatite crystal growth following direct supernate treatments was significantly inhibited by the advanced whitening dentifrice. Similarly, plaque biofilm calcification was significantly inhibited by supernate treatments of the advanced whitening dentifrice. In both protocols, the advanced whitening dentifrice produced activity similar to formulations clinically proven for antitartar activity. These results provide support for the antitartar clinical activity of this new dentifrice.

Biofilms↗
PubMed2001

Removal of extrinsic stain using a tartar control whitening dentifrice: a randomized clinical trial.

A nine-week, double blind clinical trial was conducted to evaluate the effectiveness of a novel tartar control whitening dentifrice with a silica-based abrasive system on induced dental stain. The study model involved three weeks of stain induction followed by six weeks of unsupervised brushing to assess efficacy. To induce stain, 222 healthy adult volunteers received a dental prophylaxis, and then began a limited brushing regimen supplemented by three-times daily rinsing with tea and once daily rinsing with 15 ml of 0.12% chlorhexidine. This regimen was suspended, and 187 subjects with tooth stain were entered into a six-week clinical trial where they were randomized to either a silica-based tartar control whitening dentifrice or a marketed regular dentifrice control, balancing for stain levels and smoking status. At baseline, three and six weeks, stain area and stain intensity were measured on the 8 anterior teeth using the Lobene Index. After six weeks' use, composite Lobene means were 35% lower for the whitening dentifrice compared to the regular control. In addition to the overall reductions, there were statistically significant reductions in stain area (p < 0.015) and stain intensity (p < 0.01) at both three and six weeks. The tartar control whitening dentifrice was effective in removing stain on the gingival margins and elsewhere on the body of the tooth. Safety profiles for the two test dentifrices were generally similar. After three and six weeks' use, the tartar control whitening dentifrice reduced chlorhexidine and tea stain compared to the marketed control.

Adult↗
PubMed2000

Structure of the bacteriophage lambda Ser/Thr protein phosphatase with sulfate ion bound in two coordination modes.

The protein phosphatase encoded by bacteriophage lambda (lambda PP) belongs to a family of Ser/Thr phosphatases (Ser/Thr PPases) that includes the eukaryotic protein phosphatases 1 (PP1), 2A (PP2A), and 2B (calcineurin). These Ser/Thr PPases and the related purple acid phosphatases (PAPs) contain a conserved phosphoesterase sequence motif that binds a dinuclear metal center. The mechanisms of phosphoester hydrolysis by these enzymes are beginning to be unraveled. To utilize lambda PP more effectively as a model for probing the catalytic mechanism of the Ser/Thr PPases, we have determined its crystal structure to 2.15 A resolution. The overall fold resembles that of PP1 and calcineurin, including a conserved beta alpha beta alpha beta structure that comprises the phosphoesterase motif. Substrates and inhibitors probably bind in a narrow surface groove that houses the active site dinuclear Mn(II) center. The arrangement of metal ligands is similar to that in PP1, calcineurin, and PAP, and a bound sulfate ion is present in two novel coordination modes. In two of the three molecules in the crystallographic asymmetric unit, sulfate is coordinated to Mn2 in a monodentate, terminal fashion, and the two Mn(II) ions are bridged by a solvent molecule. Two additional solvent molecules are coordinated to Mn1. In the third molecule, the sulfate ion is triply coordinated to the metal center with one oxygen coordinated to both Mn(II) ions, one oxygen coordinated to Mn1, and one oxygen coordinated to Mn2. The sulfate in this coordination mode displaces the bridging ligand and one of the terminal solvent ligands. In both sulfate coordination modes, the sulfate ion is stabilized by hydrogen bonding interactions with conserved arginine residues, Arg 53 and Arg 162. The two different active site structures provide models for intermediates in phosphoester hydrolysis and suggest specific mechanistic roles for conserved residues.

Bacteriophage lambda↗
PubMed2000

Anticalculus effects of a novel, dual-phase polypyrophosphate dentifrice: chemical basis, mechanism, and clinical response.

A primary patient motivation for oral hygiene is effective cleaning. Dentifrice serves this function by including ingredients such as abrasives, surfactants, and specialized cleaning ingredients such as anticalculus agents. This introductory article aims to introduce professionals, educators, and researchers on the rationale behind the development of an improved cleaning dentifrice formulation, Crest Multicare Advanced Cleaning. This new dentifrice is based upon the application of an improved tartar control/cleaning ingredient that is a polymeric adjunct of a pyrophosphate anion commonly applied in tartar control and stain control whitening dentifrices. The polypyrophosphate anion, also referred to as sodium hexametaphosphate, produces superior activity and substantivity on oral surfaces as compared to both pyrophosphate and some other commonly used dental cleaning ingredients and cleaning/conditioning adjuncts. The increased activity and substantivity translate into significant improvements in the prevention of dental stains and supragingival calculus and in the non-abrasive removal of dental stains. This article describes the structure of polypyrophosphate as compared to the parent pyrophosphate molecule, the rationale for its improved chemistry, and, in particular, its tartar control chemistry. In addition, the fundamental mechanisms of calculus formation and inhibition are reviewed. Lastly, a preliminary clinical study evaluating the improved efficacy of a polypyrophosphate dentifrice is described where the tartar control activity of the polypyrophosphate dentifrice is shown to be superior to that of a clinically established and marketed industry standard pyrophosphate dentifrice.

Adult↗
PubMed2000

Life-supporting human complement regulator decay accelerating factor transgenic pig liver xenograft maintains the metabolic function and coagulation in the nonhuman primate for up to 8 days.

BACKGROUND: It is not known whether the pig liver is capable of functioning efficiently when transplanted into a primate, neither is there experience in transplanting a liver from a transgenic pigs expressing the human complement regulator human complement regulator decay accelerating factor (h-DAF) into a baboon. The objective of this study was to determine whether the porcine liver would support the metabolic functions of non-human primates and to establish the effect of hDAF expression in the prevention of hyperacute rejection of porcine livers transplanted into primates. METHODS: Five orthotopic liver xenotransplants from pig to baboon were carried out: three from unmodified pigs and two using livers from h-DAF transgenic pigs. FINDINGS: The three control animals transplanted with livers from unmodified pigs survived for less than 12 hr. Baboons transplanted with livers from h-DAF transgenic pigs survived for 4 and 8 days. Hyperacute rejection was not detected in the baboons transplanted with hDAF transgenic pig livers; however, it was demonstrated in the three transplants from unmodified pigs. Baboons transplanted with livers from h-DAF transgenic pigs were extubated at postoperative day 1 and were awake and able to eat and drink. In the recipients of hDAF transgenic pig livers the clotting parameters reached nearly normal levels at day 2 after transplantation and remained normal up to the end of the experiments. In these hDAF liver recipients, porcine fibrinogen was first detected in the baboon plasma 2 hr postreperfusion, and was present up to the end of the experiments. One animal was euthanized at day 8 after development of sepsis and coagulopathy, the other animal arrested at day 4, after an episode of vomiting and aspiration. The postmortem examination of the hDAF transgenic liver xenografts did not demonstrate rejection. INTERPRETATION: The livers from h-DAF transgenic pigs did not undergo hyperacute rejection after orthotopic xenotransplantation in baboons. When HAR is abrogated, the porcine liver maintains sufficient coagulation and protein levels in the baboon up to 8 days after OLT.

Acute Disease↗
PubMed2000

Concentrations of nevirapine, lamivudine and stavudine in semen of HIV-1-infected men.

OBJECTIVE: To determine the concentrations of nevirapine (NVP), lamivudine (3TC) and stavudine (D4T) in seminal and blood plasma in HIV-1-infected men. METHODS: Twelve HIV-1-infected men on NVP-containing regimens including 3TC (n = 8) or D4T (n = 11) provided 23 blood plasma and 22 seminal plasma samples for drug concentration and viral load quantitation. Concentrations of all drugs were assessed by sensitive validated high performance liquid chromatography (HPLC) assays. Blood plasma and seminal plasma viral loads were measured using nucleic acid sequence-based amplification (NASBA). Samples were grouped according to time after drug ingestion, 0-2, 2-4, 4-8 and 8-12 h. For matched seminal and blood plasma samples, obtained within 1 h of each other, a seminal:blood plasma ratio was calculated. RESULTS: The concentration of NVP in seminal plasma appeared to mirror the concentrations in blood plasma. Absolute median seminal plasma NVP concentrations at 0-2, 2-4, 4-8 and 8-12 h were 3.1 microg/ml (range 1.7-4.89), 2.68 microg/ml (2.5-3.9), 2.5 microg/ml (2.3-2.7) and 3.09 microg/ml (1.3-9.1). The median seminal:blood plasma ratios for the four time periods were 0.54 (range 0.34-0.85), 0.83 (range 0.43-1.08), 0.53 (0.48-0.59), and 0.61 (0.59-0.78). 3TC and D4T appeared to reach concentrations in seminal plasma of a similar magnitude or higher than concentrations in blood plasma. The median seminal plasma viral load for all patients was less than 800 copies/ml (range < 800-11000). The median blood plasma viral load was less than 400 copies/ml (< 400-1100). CONCLUSION: NVP reaches concentrations in the semen approximately 60% of those in the blood plasma throughout the 12 h dosing period. In a smaller dataset, 3TC and D4T concentrations in blood plasma and seminal plasma were similar. These data may well have implications for the evolution of drug-resistant virus within the genital tract.

Adult↗
PubMed2000

Long-term survival of nonhuman primates receiving life-supporting transgenic porcine kidney xenografts.

BACKGROUND: Recently, there has been a resumed interest in clinical xenotransplantation using pig organs. However, no data are available yet regarding the capacity of porcine organs to sustain the life of a primate beyond the first month. We have attempted to obtain long-term survival of nonhuman primates using human decay-accelerating factor (hDAF) transgenic pig organs and an immunosuppressive strategy particularly aimed at neutralizing the humoral component of the immune response. METHODS: hDAF transgenic or control kidneys were transplanted into 14 bilaterally nephrectomized cynomolgus monkeys (Macaca fascicularis) that underwent splenectomy and were immunosuppressed with cyclosporine A, cyclophosphamide, and steroids. All animals also received recombinant erythropoietin. Postoperatively, the primates were monitored daily. Laboratory evaluations included serum biochemistry, hematology, and measurements of hemolytic antipig antibodies. To assess the role of splenectomy in the control of humoral response, historical data were also used from a group of monkeys (n=7) that received the same immunosuppressive regimen and an hDAF transgenic porcine kidney but did not have splenectomy or receive recombinant erythropoietin. RESULTS: This immunosuppressive approach obtained the longest survival time (78 days) described to date of a primate receiving a life-supporting porcine renal xenograft. Furthermore, four of nine animals in this series survived for 50 days or more. Most biochemical measurements in this study (including plasma urea, creatinine, sodium, and potassium concentrations) remained within normal ranges for several weeks in all of the longest-surviving animals. CONCLUSIONS: Normalization of renal function (urea and creatinine) in primate recipients of porcine renal xenografts suggests that pig kidneys may be suitable for future clinical xenotransplantation. Additional immunosuppressive approaches, specifically designed to prevent humorally mediated immunological damage, should be explored to further prolong survival of primates that have received porcine xenografts.

Animals↗
PubMed2000

Damage to porcine islets of Langerhans after exposure to human blood in vitro, or after intraportal transplantation to cynomologus monkeys: protective effects of sCR1 and heparin.

BACKGROUND: Porcine islets offer an attractive alternative to human islets in clinical islet transplantation. The preferred method of islet transplantation is intra-portal injection into the liver. We have recently shown, both in vitro with human islets and in vivo with porcine islets, that islets exposed to allogeneic blood trigger an injurious inflammatory reaction characterized by activation of both coagulation and the complement systems. We have now tested whether a similar reaction is triggered when xenogeneic porcine islets are exposed to human blood in vitro and after intraportal transplantation into primates. Furthermore, we investigated the effect of inhibiting the complement and coagulation systems. METHOD: Islets isolated from adult and fetal porcine pancreas were perfused with fresh human blood in surface heparinized PVC tubings for 5-60 min. Blood cell counts and parameters related to coagulation and the complement system were analyzed, and islets were retrieved after the perifusion was examined by immunohistochemical method. Heparin and soluble complement receptor 1 (sCR1; TP10, 100 microg/ml) were added to the system in some experiments. Furthermore, adult porcine islets were transplanted intraportally into untreated and sCR1- (40 mg/kg BW i.v.) treated cynomolgus monkeys, and plasma insulin concentration was monitored during 60 min after transplantation. RESULTS: Porcine islets perifused with human blood triggered an immediate inflammatory reaction, characterized by a rapid consumption and activation of platelets, consumption of neutrophils and monocytes, activation of the coagulation and complement systems, and release of large amounts of insulin. Islet morphologic analysis revealed damaged islets embedded in clots and infiltrated with CD11+ leukocytes. C3a and C5b-9 was deposited on the islet surface, but human immunoglobulin was not. Complement inhibition with sCR1 reduced insulin release significantly. Intraportal islet transplantation into untreated cynomolgus monkeys resulted in a marked and rapid increase in plasma insulin concentration indicative of islet damage. Pretreatment of the monkeys with sCR1 resulted in significantly less insulin release than in untreated control monkeys. CONCLUSION: Exposure of isolated xenogeneic islets of Langerhans to blood, both in vitro and in vivo, resulted in acute islet damage. Complement and platelets seem to have a central role in the reactions described. Strategies to efficiently inhibit these reactions will be crucial for clinical intraportal islet xenotransplantation to be successful.

Animals↗