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Biomedical subjects

H Gilbert

Publications and source records attributed to H Gilbert.

At least 19 recordsLinked to original sources
PubMed2001

Tenofovir, adefovir, and zidovudine susceptibilities of primary human immunodeficiency virus type 1 isolates with non-B subtypes or nucleoside resistance.

New antiretroviral drugs with activity against strains of human immunodeficiency virus type 1 (HIV-1) with non-B subtypes and with resistance to current antiretroviral drugs are needed. The activity of two nucleotide analogs, tenofovir and adefovir (PMPA and PMEA, respectively), against non-B subtypes and nucleoside-resistant primary HIV-1 isolates was assessed. Tenofovir and adefovir were fully active against a panel of subtypes A, C, D, E, F, G, and group O primary HIV-1 isolates as compared with their respective activity against subtype B isolates. Moreover, the susceptibility of a panel of 10 primary HIV-1 isolates with >10-fold mean resistance to zidovudine, lamivudine, and abacavir was within 2.2-fold of wild-type tenofovir susceptibility for each isolate. An oral prodrug of tenofovir, tenofovir disoproxil fumarate (DF), is currently in phase III clinical trials for the treatment of HIV-1 infection. These in vitro susceptibility results suggest that tenofovir DF may be active in vivo against HIV-1 with nucleoside resistance as well as against HIV-1 with non-B subtypes.

Adenine↗
PubMed1999

Contributions of aspartate 49 and phenylalanine 142 residues of a tight binding inhibitory protein of beta-lactamases.

beta-Lactamases are bacterial enzymes that hydrolyze beta-lactam antibiotics to render them inactive. The beta-lactamase inhibitor protein (BLIP) of Streptomyces clavuligerus, is a potent inhibitor of several beta-lactamases, including the TEM-1 enzyme (Ki = 0.6 nM). Evidence from the TEM-1/BLIP co-crystal suggests that two BLIP residues, Asp-49 and Phe-142, mimic interactions made by penicillin G when bound in the active site of TEM-1. To determine the importance of these two residues, a heterologous expression system for BLIP was established in Escherichia coli. Site-directed mutagenesis was used to change Asp-49 and Phe-142 to alanine, and inhibition constants (Ki) for both mutants were determined. Each mutation increases the Ki for BLIP inhibition of TEM-1 beta-lactamase approximately 100-fold. To address how these two positions effect the specificity of beta-lactamase binding, Ki values were determined for the interaction of wild-type BLIP, as well as the D49A and F142A mutants, with two extended spectrum beta-lactamases (the G238S and the E104K TEM variants). Positions 104 and 238 are located in the BLIP/beta-lactamase interface. Interestingly, the three BLIP proteins inhibited the G238S beta-lactamase mutant to the same degree that they inhibited TEM-1. However, wild-type BLIP has a higher Ki for the E104K beta-lactamase mutant, suggesting that interactions between BLIP and beta-lactamase residue Glu-104 are important for wild-type levels of BLIP inhibition.

Aspartic Acid↗
PubMed1999

Analysis of factor structure in a dream inventory.

Intercorrelations of responses to the KJP dream inventory, initially a checklist of dream elements, were factor analyzed from a database from 65 graduate majors in psychology. Six factors were identified within the checklist: repetitive traumatic dreaming, reoccurring pleasantness, openness or depth, discontentedness, dissociative avoidance, and uninhibitedness. Scoring criteria were developed for each subscale.

Adult↗
PubMed1998

Mantle discontinuity structure beneath the southern east pacific rise from P-to-S converted phases

Receiver functions derived from teleseismic body waves recorded by ocean-bottom seismometers on the southern East Pacific Rise reveal shear waves converted from compressional waves at the mantle discontinuities near 410- and 660-kilometer depth. The thickness of the mantle transition zone between the two discontinuities is normal relative to the global average and indicates that upwelling beneath the southern East Pacific Rise is not associated with an excess temperature in the mantle transition zone.

Journal Article↗
PubMed1998

The cloned capsaicin receptor integrates multiple pain-producing stimuli.

Capsaicin, the main pungent ingredient in "hot" chili peppers, elicits buming pain by activating specific (vanilloid) receptors on sensory nerve endings. The cloned vanilloid receptor (VR1) is a cation channel that is also activated by noxious heat. Here, analysis of heat-evoked single channel currents in excised membrane patches suggests that heat gates VR1 directly. We also show that protons decrease the temperature threshold for VR1 activation such that even moderately acidic conditions (pH < or = 5.9) activate VR1 at room temperature. VR1 can therefore be viewed as a molecular integrator of chemical and physical stimuli that elicit pain. Immunocytochemical analysis indicates that the receptor is located in a neurochemically heterogeneous population of small diameter primary afferent fibers. A role for VR1 in injury-induced hypersensitivity at the level of the sensory neuron is presented.

Afferent Pathways↗
PubMed1998

Antimicrobial resistance of clinical strains of Campylobacter jejuni subsp. jejuni isolated from 1985 to 1997 in Quebec, Canada.

The antimicrobial resistance of 158 Campylobacter jejuni strains isolated from humans in Quebec, Canada, from 1995 to 1997 was compared to the resistance of 47 and 86 strains of C. jejuni isolated in 1985 and 1986 and in 1992 and 1993, respectively. Of the 291 C. jejuni strains tested, no strain was resistant to erythromycin. Compared to the C. jejuni strains isolated in 1985 and 1986, the C. jejuni strains isolated in 1992 and 1993 were more resistant to tetracycline (40.7 versus 19.1%, respectively; P = 0. 01) but not to nalidixic acid or ciprofloxacin (P > 0.05). Compared to the C. jejuni strains isolated in 1992 and 1993 and in 1985 and 1986, the C. jejuni strains isolated from 1995 to 1997 were more resistant to tetracycline (55.7% versus 40.7 and 19.1%, respectively; P = 0.03 and P < 0.001, respectively) to nalidixic acid (13.9% versus 4.7 and 0%, respectively; P = 0.02 and P = 0.007, respectively), and to ciprofloxacin (12.7% versus 3.5 and 0%, respectively; P = 0.02 and P = 0.009, respectively).

Campylobacter jejuni↗
PubMed1997

Comparison of disc diffusion and agar dilution methods for antibiotic susceptibility testing of Campylobacter jejuni subsp. jejuni and Campylobacter coli.

The correlation between disc diffusion and agar dilution susceptibility testing of five antibiotics was studied against 145 Campylobacter strains: 99 Campylobacter jejuni subsp. jejuni and 46 Campylobacter coli. The percentages of true results and 95% CI for disc diffusion for resistant strains were 100% (93.2-100%) for tetracycline (53 strains tested), 100% (77.2-100%) for ciprofloxacin (13 strains tested), 86.7% (62.1-96.3%) for nalidixic acid (15 strains tested), 100% (56.6-100%) for erythromycin (five strains tested) and 68.8% (44.4-85.8%) for ampicillin (16 strains tested). The percentages of true results and 95% CI were 97.6-100% and 93.2-100% respectively for 89-140 susceptible strains to the five antibiotics tested. There was a 1.4% major error for nalidixic acid, 0.7% very major error for erythromycin, 5.5% and 1.4% minor and major errors respectively for ampicillin. There was complete agreement for ciprofloxacin and tetracycline. Results of ampicillin susceptibility are not expected to be useful in a clinical setting. The nalidixic acid disc is a marker of ciprofloxacin susceptibility as the nalidixic acid-susceptible strains were susceptible to ciprofloxacin while most of the resistant ones were resistant to ciprofloxacin. Overall, our results suggest that disc diffusion is a reliable, easy and inexpensive susceptibility testing method for C. jejuni and C. coli for erythromycin, ciprofloxacin and tetracycline. Until more erythromycin- and ciprofloxacin-resistant strains are tested to confirm the reliability of this test, the resistance to these drugs needs to be confirmed using the Etest or the agar dilution method.

Ampicillin↗
PubMed1994

Angelman syndrome associated with a maternal 15q11-13 deletion of less than 200 kb.

Angelman syndrome (AS) is a neurogenetic disorder arising from a lack of genetic contribution from the maternal chromosome 15q11-13. To date, the AS critical region has been defined by an inherited deletion of approximately 1.5Mb, spanning the 3-21 (D15S10), LS6-1 (D15S113) and GABRB3 loci. We have identified an individual with the typical features of AS who has a deletion of the maternal chromosome which encompasses LS6-1, but does not extend to either flanking marker. This deletion, initially detected by (CA)n repeat analysis, was further characterised by fluorescence in situ hybridisation (FISH) using cosmids derived from a 260 kb LS6-1 yeast artificial chromosome (YAC). Neither end cosmid from this YAC clone falls within the deletion, suggesting that the minimal AS region is less than 200 kb. We also studied three loci within 15q11-13 which detect parent-of-origin specific DNA methylation imprints, and found that both normal maternal and paternal patterns were present in this patient.

Angelman Syndrome↗
PubMed1992

Survey of Bacteroides fragilis group susceptibility patterns in Canada.

The in vitro activities of penicillin, clindamycin, chloramphenicol, metronidazole, piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin-sulbactam, cefoxitin, ceftizoxime, cefotetan, moxalactam, and imipenem against 348 Bacteroides fragilis group isolates collected from six Canadian cities during 1990 were determined by the National Committee for Clinical Laboratory Standards (NCCLS) agar dilution technique. All isolates were susceptible to chloramphenicol, metronidazole, piperacillin-tazobactam, and imipenem. For the other antibiotics tested, the following resistance rates were observed: penicillin, 97%; clindamycin, 9%; piperacillin, 19%; ticarcillin, 31%; ticarcillin-clavulanate, 0.28%; ampicillin-sulbactam, 0.85%; cefoxitin, 26%; ceftizoxime, 15%; cefotetan, 53%; and moxalactam, 17%. Susceptibility profiles to beta-lactam antibiotics varied among the different species tested: B. fragilis and Bacteroides vulgatus demonstrated lower resistance rates than Bacteroides distasonis and indole-positive Bacteroides thetaiotaomicron and Bacteroides ovatus. Ceftizoxime results should be interpreted cautiously, because the MICs obtained with the recommended NCCLS control strain were lower than expected.

Anti-Bacterial Agents↗
PubMed1989

Activation of human neutrophil NADPH-oxidase in vitro by the catalytic fragment of protein kinase-C.

Phorbol ester treatment of intact neutrophils both stimulates protein kinase C (PK-C) and causes the rapid proteolytic conversion to a cytosolic, co-factor independent fragment, protein kinase M (PK-M). In intact neutrophils, phorbol ester treatment activates the NADPH-oxidase, the enzyme responsible for the oxidative burst. Addition of purified PK-M to resting neutrophil light density membranes activated the NADPH-oxidase in the presence of PS, ATP and Mg2+. A 3.5-fold greater stimulation of oxidase (ca. 25 nmoles O2-/min/mg membrane protein) was obtained with comparable PK-M concentrations to that observed with the reconstituted PK-C system, and approximately 1/3 that obtained with arachidonic acid (AA) or SDS. In contrast to the reconstituted system using PK-C, PMA and Ca++ were neither required nor affected activity. The effect of PS was unexpected, since PK-M does not require phospholipids for enzymatic activity, and likely represents the action of PS on the oxidase itself or on another component in the plasma membrane fraction. Our studies demonstrate for the first time that purified PK-M permits reconstitution of a physiologic phorbol ester response.

Adenosine Triphosphate↗
PubMed1985

Massive hepatic necrosis after chemotherapy withdrawal in a hepatitis B virus carrier.

A chronic hepatitis B virus (HBV) carrier with diffuse nodular transformation of the liver and malignant lymphoma in the lymph nodes and spleen developed massive hepatic necrosis and died three weeks after the third cycle of chemotherapy. Immunosuppressive drug treatment may favor replication of HBV, resulting in massive hepatocyte destruction when the immune response recovers following withdrawal of chemotherapy. This outcome must be considered in patients with chronic hepatitis B who are treated with a course of prednisone followed by antiviral therapy as well as in HBV carriers following chemotherapy for malignant disease.

Antineoplastic Agents↗
PubMed1984

Multiple evanescent white dot syndrome. I. Clinical findings.

We examined 11 young patients with unilateral ocular findings that included multiple white dots at the level of the retinal pigment epithelium (RPE) or the deep retina, vitreal cells, RPE granularity in the macula, reduced visual acuity, electroretinogram (ERG) and early receptor potential (ERP) amplitudes, and fluorescein leakage from disc capillaries and late staining of the RPE. Recovery of visual function included a dramatic improvement in ERG and ERP amplitudes over several weeks. The etiology of this syndrome remains uncertain; there is no definite evidence of systemic involvement.

Adolescent↗
PubMed1983

Increased serum procollagen III aminoterminal peptide in myelofibrosis.

Myelofibrosis has been shown to involve an increase in type III collagen in the marrow. The aminoterminal procollagen III (PC III) peptide fragment is released during the production of PC III by fibroblasts and its serum level is therefore a marker for type III collagen synthesis. Using a recently developed sensitive radioimmunoassay, serum levels of PC III peptide were measured in 30 patients with myeloproliferative disease and 23 normal volunteers. Levels were found to be elevated above normal values in patients with polycythemia vera, even more elevated in patients with polycythemia and evidence of secondary myelofibrosis with myeloid metaplasia, and most strikingly elevated in patients with agnogenic myeloid metaplasia and severe marrow fibrosis. There was a significant association between serum levels of PC III peptide and the extent of reticulin fibrosis in bone marrow biopsies. Serum PC III level appears to be a quantitative marker for myelofibrosis.

Adult↗
PubMed1982

Rapid analysis of immunoglobulin isoelectric focusing patterns with cellulose nitrate sheets and immunoperoxidase staining.

Immunoglobulins which have been focused to their isoelectric points in thin-layer polyacrylamide gels can be transferred by diffusion to the surface of cellulose nitrate sheets with retention of the original focusing patterns. IgG can be detected with peroxidase-linked antiserum. Unlike polyacrylamide gel, cellulose nitrate offers no permeability barrier, and so washing times are reduced from days to minutes. Thus small quantities (less than 1 microgram) of IgG may be visualized within 24 h of isoelectric focusing. In addition after immobilization on cellulose nitrate, immunoglobulin reactivity with antigens, including those of high molecular weight, may be analysed.

Animals↗