Search PubMed⌕ Search

Biomedical subjects

J Hay

Publications and source records attributed to J Hay.

At least 109 records · Page 6Linked to original sources
PubMed1994

Drug resistance and Acanthamoeba keratitis: the quest for alternative antiprotozoal chemotherapy.

Trophozoites and cysts of 20 isolates of Acanthamoeba from the cornea and five from related samples were tested in vitro for sensitivity to ten drugs (three aromatic diamidines, two aminoglycosides, two macrolides, a polyene macrolide antibiotic, an organoarsenical and an antimetabolite) and two cationic antiseptics (chlorhexidine and polyhexamethylene biguanide, PHMB). Only chlorhexidine and PHMB showed uniform amoebacidal activity. Aromatic diamidines (pentamidine isethionate, propamidine isethionate and diminazene aceturate) generally proved effective against both forms of the amoeba; only pentamidine gave synergy with the biguanide while propamidine gave an additive effect. Other drugs tested proved erratic or ineffective against different isolates. Chlorhexidine alone, or together with propamidine, was subsequently used in two patients with proven Acanthamoeba keratitis; the causative isolates were sensitive to the individual compounds and to the combination in vitro. The treatment provided resolution of the clinical disease; amoebae were shown to be nonviable by histology and culture. The combination of chlorhexidine and propamidine is recommended for treatment of proven Acanthamoeba keratitis.

Acanthamoeba↗
PubMed1994

Defective transport of herpes simplex virus glycoprotein in interferon-treated cells: role of intracellular pH.

We have investigated the mechanism(s) of interferon (IFN)-induced inhibition of assembly steps of herpes simplex virus (HSV-1) in mouse LB cells. Data showed that physiological doses of mouse IFN-beta (10-100 IU/ml) significantly inhibited the infectivity (5- to 100-fold) of HSV-1; however, viral protein synthesis was marginally inhibited (2- to 5-fold). Immunofluorescence studies showed that most of the HSV-1gD glycoprotein accumulated intracellularly in IFN-treated LB and LMtk- cells transfected with gD cDNA, as compared to untreated controls, where most of the gD was localized on the plasma membrane. Double-immunofluorescence studies demonstrated that rhodamine-labeled wheat germ agglutinin (WGA) was co-localized with gD protein, suggesting the block was in the transport from the trans-Golgi to the plasma membrane. IFN treatment of LB and LMtk- cells raised the intracellular pH as measured by DAMP distribution and SNARF-1 using laser spectroscopy; this could play an important role in the inhibition of transport of HSV-1gD.

Animals↗
PubMed1994

Membrane filtration method for bacteriological testing of water: enhanced colony visualization and stability on purification of phenol red indicator.

Commercially-available phenol red indicator, purified by adsorption chromatography was incorporated into lauryl sulphate broth (LSB) used in the membrane filtration method for the detection of Escherichia coli and other coliform bacteria. Relative to LSB containing the impure dye or its major contaminant, the purified phenol red provided clear visualization of discrete yellow colonies observed against a white background. The colonies remained stable for at least 24 h at 25 degrees C under standard laboratory lighting conditions. This simple procedure will enhance the detection of coliforms in samples.

Color↗
PubMed1994

Selective effects of pentamidine on cytosolic and granule-associated enzyme release from zymosan-activated human neutrophilic granulocytes.

Therapeutic concentrations (0.3-1.5 mgL-1) of pentamidine isethionate, normally obtainable in-vivo after parenteral administration of the drug, did not affect the in-vitro activity of the enzymes lysozyme, beta-glucuronidase or myeloperoxidase released from zymosan-activated human neutrophilic granulocytes. At concentrations of 0.7, 1.1 and 1.5 mgL-1, activity of cytosolic enzymes lactate dehydrogenase and glucose-6-phosphate dehydrogenase were reduced relative to untreated cells (P < 0.001 and P < 0.01, respectively), but not in a dose-dependent fashion. Cell viability, as determined by dye-exclusion remained unaffected.

Adult↗
PubMed1994

Naphthalene black staining of granules of eosinophilic granulocytes: proposed mechanism of action using chemical blockade and computer graphics.

Histochemical staining of the granules of eosinophilic granulocytes and subsequent blockade of the reaction by alkaline benzyl was strongly suggestive that in its purified form, the diazo dye naphthalene black reacts with tissue sites containing high concentrations of arginine residues. Computer graphics modelling indicated that the sulfonate group of the dye reacts electrostatically with the guanidino functional group of arginine. This acid-base type reaction likely has a stoichiometric ratio of 2:1 in favor of the amino acid.

Amido Black↗
PubMed1994

A cost analysis of approved antiretroviral strategies in persons with advanced human immunodeficiency virus disease and zidovudine intolerance.

Treatment with zidovudine has been standard therapy for patients with advanced HIV infection, but intolerance is common. Previously, management of intolerance has consisted of symptomatic therapy, dose interruption/discontinuation, and, when appropriate, transfusion. The availability of new antiretroviral agents such as didanosine as well as adjunctive recombinant hematopoietic growth factors makes additional strategies possible for the zidovudine-intolerant patient. Because all of these agents are costly, we evaluated the cost implications of these various strategies for the management of zidovudine-intolerant individuals within a population of persons with advanced HIV disease. We performed a decision analysis using iterative algorithmic models of 1 year of antiretroviral care under various strategies. The real costs providing antiretroviral therapy were estimated by deflating medical center charges by specific Medi-Cal (Medicaid) charge-to-payment ratios. Clinical data were extracted from the medical literature, product package inserts, investigator updates, and personal communications. Sensitivity analysis was used to test the effect of error in the estimation of parameters. The models predict that a strategy of dose interruption and transfusion for zidovudine intolerance will provide an average of 46 weeks of therapy per year to the average patient at a cost of $5,555/year of therapy provided (1991 U.S. dollars). The models predict that a strategy of adding hematopoietic growth factors to the regimen of appropriate patients would increase the average amount of therapy provided to the average patient by 3 weeks (6%) and the costs attributable to therapy by 77% to $9,805/year of therapy provided.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1993

Gastric intramural pH as a predictor of success or failure in weaning patients from mechanical ventilation.

OBJECTIVE: To determine whether gastric intramural pH (pHi), an indirect measure of gastric mucosal ischemia, can be used to predict the success of weaning from mechanical ventilation. Gastric mucosal ischemia (and, therefore, acidosis) may develop in patients during unsuccessful attempts to wean them from mechanical ventilation because blood flow from nonvital areas (for example, splanchnic bed) is diverted to meet the increased demands of respiratory muscles. DESIGN: Cohort study. SETTING: Intensive care unit. PATIENTS: Twenty-nine patients receiving assisted mechanical ventilation for respiratory failure who were thought by their physicians to be weanable from mechanical ventilation. MEASUREMENTS: Simultaneous samples of arterial blood and gastric juice were obtained from patients during assisted mechanical ventilation, as well as during weaning trials. The predictor variable, pHi, was calculated using the following equation: 6.1 + log HCO3/(gastric PCO2 x 0.0307). The outcome was success or failure of weaning, decided by physicians blinded to the study. RESULTS: Patients who could not be weaned from mechanical ventilation had a substantially reduced gastric pHi (7.36 during mechanical ventilation compared with 7.09 during weaning [difference, 0.27; 95% Cl, 0.12 to 0.42; P < 0.01]). Patients who were successfully weaned from mechanical ventilation showed no change in pHi (7.45 during mechanical ventilation compared with 7.46 during weaning [difference, 0.01; Cl, -0.01 to 0.03; P = 0.29]). The sensitivity and specificity of pHi in predicting weaning success or failure were both 100% (Cl, 81 to 100 and 72 to 100, respectively). CONCLUSION: Gastrointestinal acidosis may be an early sign of weaning failure. Measurement of pHi, which is simple and rapid, may be of practical value in predicting the likelihood of weaning success or failure during weaning trials.

Acidosis↗
PubMed1993

Immunization with the immediate-early tegument protein (open reading frame 62) of varicella-zoster virus protects guinea pigs against virus challenge.

The IE62 protein, the primary regulatory protein of varicella-zoster virus (VZV) and the major component of the virion tegument, was an effective immunogen in the guinea pig model of VZV infection, whereas the ORF 29 gene product, a nonstructural DNA replication protein, did not elicit protection. All animals immunized with the ORF 29 protein had cell-associated viremia compared with 2 of 11 guinea pigs given the IE62 protein (P = 0.005). VZV was detected in ganglia from 38% of the animals given the ORF 29 protein and 44% of the control animals compared with 9% of the animals immunized with the IE62 protein (P = 0.04). In contrast to the IE62 protein, immunization with the ORF 29 protein did not prime the animals for an enhanced T-cell response upon challenge with infectious virus. The VZV IE62 protein has potential value as a vaccine component.

Animals↗
PubMed1993

A major transactivator of varicella-zoster virus, the immediate-early protein IE62, contains a potent N-terminal activation domain.

Accumulating evidence indicates that the product of the putative immediate-early gene ORF62 (IE62) activates varicella-zoster virus (VZV) genes thought to represent all three kinetic classes, namely, immediate-early (alpha), early (beta), and late (gamma) classes, of VZV genes as well as a variety heterologous gene promoters. However, the mechanism(s) by which IE62 protein mediates transactivation of these diverse VZV and heterologous gene promoters remains to be elucidated. In this study, by using yeast GAL4 protein chimeras, the coding regions of VZV ORF62 possessing activation domains have been assessed. We demonstrate that the VZV IE62 protein contains a potent activation domain in the N-terminal portion of the molecule, encoded within the first 86 codons of ORF62. The predicted secondary structure profile and the acid-base composition of this IE62 domain resemble those of other transregulatory proteins whose activation is mediated through acidic, hydrophobic elements. In addition, we show that deletion of this activation domain from the 1,310-residue native IE62 protein results in ablation of the transactivator function of IE62. We also present evidence that the mutant IE62 protein lacking the activation domain, though devoid of transactivation ability, was still capable of interfering with the activation of target promoters by the native, full-length IE62.

Amino Acid Sequence↗
PubMed1992

The varicella-zoster virus immediate early protein, IE62, can positively regulate its cognate promoter.

Varicella-Zoster virus (VZV) is a neurotropic alphaherpes virus closely related to herpes simplex virus (HSV). However, unlike its close relative HSV, VZV lacks a functional alpha-TIF (alpha-gene transinducing factor) that activates the transcription of immediate early genes during the initial events of the virus life cycle. Hence, in the absence of a functional alpha-TIF, the mechanism triggering the expression of immediate early genes in VZV at present remains unclear. Accumulating evidence indicates that the gene product of the putative immediate early gene ORF62 (IE62) plays a pivotal role in activating VZV genes of all three putative kinetic classes, namely immediate early (alpha), early (beta), and late (gamma) classes of VZV genes. In the present study, we show that IE62 can positively autoregulate its cognate promoter using a transient transfection assay, both in lymphocytes and in neural cells. In the same system, we can also demonstrate activation of the VZV IE62 promoter by HSV ICP4. By deletion analysis and oligonucleotide-directed site-specific mutagenesis we have localized specific regions in the IE62 promoter/upstream sequences that mediate inducibility by IE62 and HSV ICP4, and provide evidence that this promoter activation by these two proteins may be through different mechanisms. These data, taken together with the recent demonstration of the presence of IE62 in the VZ virion tegument (Kinchington, P.R., Hoagland, J.K., Arvin, A.M., Ruyechan, W.T., and Hay, J. 1992. J. Virol. 66, 359-366) provides a possible mechanism by which the triggering of VZV gene expression occurs in the absence of a functional alpha-TIF protein.

Animals↗