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Biomedical subjects

D J Myers

Publications and source records attributed to D J Myers.

At least 19 recordsLinked to original sources
PubMed2001

Respiratory health of automobile workers and exposures to metal-working fluid aerosols: lung spirometry.

BACKGROUND: Despite substantial evidence that workers exposed to metal-working fluids (MWF) have increased respiratory morbidity, the few studies of chronic effects on lung function have not been conclusive. METHODS: Lung spirometry was measured and both current and past exposures to metal-working fluid (MWF) aerosols were estimated in this cross-sectional cohort of 1,811 male automobile workers. Satisfactory exposure data were available for 1,745 (96%): 239 assemblers (never-exposed to MWF), 487 assemblers (previously exposed), 352 machinists currently exposed to straight oils, 441 to soluble oils, and 226 to synthetic fluids. Operations were classified as either grinding or non-grinding machining. RESULTS: Current exposure was not found to be associated with either forced expiratory volume in 1 second (FEV(1)) or forced ventilatory capacity (FVC). Nor was past exposure to water-based fluids (soluble or synthetic MWF) related to pulmonary function. Past exposure to straight oils, however, was significantly associated with FVC. This association was more obvious among older workers and among workers who had never transferred from MWF exposed jobs to assembly. CONCLUSIONS: The magnitude of the association between FVC and lifetime exposure to straight MWF was slightly larger than the estimated cigarette effect, suggesting that the impact of an additional year of exposure to 1 mg/m(3) of mineral oil particulate in the thoracic particle size range, has the same impact on FVC as smoking one pack per day for one more year.

Adult↗
PubMed1997

Synergistic inhibition of calcification of porcine aortic root with preincubation in FeCl3 and alpha-amino oleic acid in a rat subdermal model.

Postimplant calcific degeneration is a frequent cause of clinical failure of glutaraldehyde crosslinked porcine aortic valve bioprostheses. We demonstrated previously in rat subdermal and circulatory implants that alpha-amino oleic acid used as a bioprosthesis pretreatment was highly effective in mitigating aortic valve cusp but not aortic wall calcification. In this study we investigated the feasibility of synergistically applying two proven anticalcification agents (alpha-amino oleic acid and FeCl3) as pretreatments for mitigating both bioprosthetic cusp and aortic wall calcification. alpha-Amino oleic acid is hypothesized to prevent calcification by disrupting calcium phosphate formation kinetics, whereas suppression of alkaline phosphatase activity and ferric-phosphate complexation at a cellular membrane initiation sites may be important factors in ferric ion's inhibition of calcification. In vivo implant studies (21-day rat subdermal model) indicated that individually FeCl3 (0.01 or 0.1 M for 24 h) or alpha-amino oleic acid (saturated solution) treatments were equally effective in mitigating cuspal calcification (tissue calcium levels: 30.2 +/- 10.2, 29.8 +/- 2.7, and 31.6 +/- 7.8 micrograms/mg tissue, respectively). However, sequential application of first alpha-amino oleic acid and then FeCl3 synergistically reduced aortic wall calcification more effectively than either of the agents alone. The benefit of a synergistic application of two anticalcification treatments, alpha-amino oleic acid and FeCl3, was demonstrated. However, the synergistic effect was observed on aortic wall only at a higher FeCl3 concentration. (i.e., 0.1 M).

Animals↗
PubMed1997

Allogeneic peripheral blood stem cell transplant for myelodysplasia after chemotherapy for post-transplant lymphoma in a cardiac transplant recipient at 10 years.

A 32-year-old male received an allogeneic peripheral blood stem cell transplant (alloPBSCT) for myelodysplasia from his one HLA-A antigen mismatched brother. He is alive with trilineage engraftment and without active GVHD 200 days after transplant. In July 1986 he underwent orthotopic cardiac transplantation for viral cardiomyopathy and has received continuous immunosuppressive therapy. A post-transplant lymphoproliferative disorder with Hodgkin-like histopathology was diagnosed in August 1993 and was successfully treated with four cycles of MOPP chemotherapy. Due to persistent pancytopenia he underwent a bone marrow aspiration and biopsy in May 1996 which revealed monosomy 7 and morphologic changes compatible with myelodysplasia. This is the first report of a cardiac transplant recipient receiving an allogeneic hematopoietic stem cell transplant.

Adult↗
PubMed1995

Asthma symptoms and airway hyperresponsiveness are lower during treatment with nedocromil sodium than during treatment with regular inhaled albuterol.

In a double-blind, double-dummy, multicenter study, 212 patients with asthma whose symptoms were not controlled by as-needed use of inhaled bronchodilators were randomized to receive either 4 mg of nedocromil sodium or 180 micrograms of albuterol four times daily for 12 weeks. Asthma symptom scores (daytime asthma, nighttime asthma, morning chest tightness, and cough) and peak expiratory flow rate were recorded daily on diary cards. Bronchial hyperresponsiveness was assessed by changes in diurnal variation in peak expiratory flow rate and by methacholine inhalation challenge. Statistically significant differences were found between groups favoring nedocromil sodium for relief of day and nighttime asthma and morning chest tightness. Patients treated with nedocromil sodium also had significantly lower diurnal variation in peak expiratory flow rate compared with patients treated with albuterol. Compared with patients treated with albuterol, patients treated with nedocromil sodium showed a greater improvement in cough and a decreased sensitivity to methacholine challenge. Patients in both groups reduced their as-needed albuterol use. Regular treatment with nedocromil sodium therefore led to greater asthma symptom control and reduced bronchial responsiveness compared with regular treatment with albuterol. The study also showed that more frequent use of a beta 2-agonist (for symptom relief or not) did not improve asthma control. Both drugs were well tolerated.

Administration, Inhalation↗
PubMed1995

Fatal clival subdural hematoma in a hemophiliac.

We report the case of a hemophiliac in whom developed an unusual site of intracranial bleeding, a subdural hematoma that extended in the posterior fossa anteriorly from the clivus into the upper spinal subdural space. The hematoma was delayed in onset and was fatal. We review the current management recommendations for hemophiliac patients with head injury and the clinical presentation of intracranial bleeding in hemophiliacs. The necessity for Factor VIII replacement and serial computed tomography scans is emphasized.

Adolescent↗
PubMed1995

Application of a competitive ELISA for the detection of bluetongue virus antibodies in llamas and wild ruminants.

A competitive enzyme-linked immunosorbent assay (C-ELISA), using a group-specific monoclonal antibody against bluetongue virus (BTV), was applied to detect anti-BTV antibodies in serum samples from two llamas (Llama glama) experimentally infected with BTV serotype 10. Antibodies were detected in both llamas by 1 wk or 2 wk post-infection. Antibodies to BTV increased exponentially during the first 4 wk in both llamas and stabilized at an elevated level during the remaining 5-wk-period of the experiment. We evaluated the C-ELISA for 1,442 field sera from bluetongue-free areas, collected from 398 llamas in New Zealand as well as 451 elk (Cervus elaphus canadensis), 323 bison (Bison bison) and 270 reindeer (Rangifer tarandus tarandus) in Canada. Based on the frequency distribution of the C-ELISA values, we propose that the current negative cut-off value of 50% inhibition established for bovine field sera also can be applied to the sera from these wild ruminants. The C-ELISA values for other wild ruminant field sera collected in bluetongue-free areas of Canada from 98 native caribou (Rangifer tarandus caribou), 32 white-tailed deer (Odocoileus virginianus), 14 moose (Alces alces), and nine musk-oxen (Ovibos maschatus) and 15 yak (Bos grunniens) also were less than 50%, with the exception of three caribou samples. Based on our results, we propose that the C-ELISA be used as a rapid and specific test for serodiagnosis of BTV infection in llamas and possibly other wild ruminants.

Animals↗
PubMed1995

A comparison between glutaraldehyde and diepoxide-fixed stentless porcine aortic valves: biochemical and mechanical characterization and resistance to mineralization.

As previously reported, we found that the fixation rate and thermal denaturation (shrink) temperature of the diepoxide-fixed tissue could be controlled by varying the concentration of the fixative as well as by adding alcohol and/or sodium chloride to the solution. In contrast to prior experience, however, we now found that the epoxide-fixed leaflets exhibited significantly higher resistance to mineralization compared to controls, but only when the tissue had not been exposed to phosphate ion.

Animals↗
PubMed1994

Cloning, chromosomal location, and characterization of mouse E2F1.

E2F has been implicated in growth control because of its association with the retinoblastoma protein and the presence of E2F binding sites in the promoters of several growth-regulated genes. Proteins that bind to an E2F site have been cloned from human and mouse cells. However, these two proteins (human E2F1 and mouse DP-1) are quite different in sequence. We have now cloned a mouse cDNA encoding a protein 86% identical to the human E2F1 protein. The mouse E2F1 cDNA encodes a 430-amino-acid protein with a predicted molecular weight of 46,322 and detects mRNAs of 2.7 and 2.2 kb. Using primers complementary to sequences in the mouse E2F1 3' untranslated region, we mapped the mouse E2F1 gene to chromosome 2, near the Agouti and c-src loci. To understand the role of the different E2F family members in the growth of mouse NIH 3T3 cells, we examined the levels of E2F1 and DP-1 mRNAs in different stages of the cell cycle. Since the levels of E2F1 but not DP-1 mRNA correlated with changes in transcription from the dhfr promoter, we examined whether E2F1 could activate various growth-regulated promoters. We found that E2F1 could activate some (dhfr, thymidine kinase, and DNA polymerase alpha) but not all (thymidylate synthase, cad, and c-myc) of these promoters. On the basis of changes in levels of E2F1 and its ability to transactivate growth-regulated promoters, we propose that E2F1 may mediate growth factor-initiated signal transduction.

Amino Acid Sequence↗
PubMed1992

Inactivation of bovine herpesvirus-1 and bovine viral diarrhea virus in association with preimplantation bovine embryos using photosensitive agents.

Hematoporphyrin (HP), hematoporphyrin derivative (HPD), and thiopyronine (TP) are photosensitive agents (PSA) that have a germicidal effect when they are activated by light: helium neon laser (He/Ne) light (HP, HPD), white light (HP, HPD), and yellow-green light (TP). Experiments were conducted with appropriate controls to determine the effect of photosensitive agents a) for inactivating bovine herpesvirus-1 (BHV-1; titre 10(6) TCID50/ml) and bovine viral diarrhea virus (BVDV; titre 10(6) TCID50/ml); b) for disinfecting Day-7, zona pellucida-intact (ZP-I) bovine embryos that had been exposed to BHV-1 (titre 10(6) TCID50/ml) or BVDV (titre 10(6) TCID50/ml); and c) on the in vitro development of embryos. Exposure to HP, HPD and TP followed by light irradiation inactivated BHV-1 and BVDV. Embryos exposed to BHV-I were disinfected by HP or HPD (5 microg/ml) in combination with He Ne light, or by HP or HPD (10 microg/ml) in combination with white light. Embryos exposed to BVDV were disinfected by HPD (5 and 10 microg/ml) followed by He Ne or white light irradiation. Exposure of embryos to light alone or to light and HP or HPD had no detrimental effect on their in vitro development; however, exposure of embryos to TP (5 microg/ml) followed by irradiation caused embryonic degeneration. Exposure of embryos to 5 microg of HPD followed by He Ne light, or 10 microg/ml of HP or HPD, followed by white light, is simple methods of disinfecting them of BHV-I and BVDV.

Journal Article↗
PubMed1992

Identification and characterization of fusion and processing domains of the human immunodeficiency virus type 2 envelope glycoprotein.

The envelope glycoprotein of the human immunodeficiency virus type 2 (HIV-2) is synthesized as a polyprotein precursor which is proteolytically processed to produce the mature surface and transmembrane envelope glycoproteins. The processed envelope glycoprotein species are responsible for the fusion between the viral envelope and the host cell membrane during the infection process. The envelope glycoprotein also induces syncytium formation between envelope-expressing cells and receptor-bearing cells. To characterize domains of the HIV-2 envelope glycoprotein involved in membrane fusion and in proteolytic processing, we introduced single amino acid mutations into the region of the HIV-2 surface glycoprotein corresponding to the principal neutralizing determinant (the V3 loop) of HIV-1, the putative HIV-2 envelope precursor-processing sequence, and the hydrophobic amino terminus of the HIV-2 transmembrane envelope glycoprotein. The effects of these mutations on syncytium formation, virus infectivity, envelope expression, envelope processing, and CD4 binding were analyzed. Our results suggest that the V3-like region of the HIV-2 surface glycoprotein and the hydrophobic amino terminus of the transmembrane glycoprotein are HIV-2 fusion domains and characterize the effects of mutations in the HIV-2 envelope glycoprotein precursor-processing sequence.

Amino Acid Sequence↗
PubMed1991

Pneumocystis carinii infection presenting as necrotizing thyroiditis and hypothyroidism.

Extrapulmonary Pneumocystis infection has been increasingly reported in patients with acquired immune deficiency syndrome (AIDS), in particular, recently in association with the increasing use of aerosolized pentamidine. This report describes the unusual presentation of extrapulmonary Pneumocystis infection as a thyroid neck mass and clinical hypothyroidism in a 37-year-old man with hemophilia and AIDS. This case differs from the previously reported single case of isolated thyroid pneumocystosis in the presence of a rapidly enlarging neck mass, lack of previous Pneumocystis, and prior prophylaxis with aerosolized pentamidine. The pathologic and electron microscopic description of the peculiar flocculent necrotic thyroid material is contrasted with typical pulmonary alveolar findings in Pneumocystis pneumonia (PCP), the differential diagnoses of a rapidly expanding neck mass, and diagnostic difficulties of hypothyroidism in patients with AIDS are discussed. Finally, it is emphasized that use of aerosolized pentamidine, although successful for prevention of pulmonary PCP, may be insufficient to prevent extrapulmonary infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Identification of the principal neutralizing determinant of human immunodeficiency virus type 1 as a fusion domain.

The V3 loop, located near the middle of the surface envelope glycoprotein gp120, is the major neutralizing domain of human immunodeficiency virus type 1 (HIV-1). Although the majority of the V3 loop is highly variable between different strains of HIV-1, a Gly-Pro-Gly-Arg motif at the tip of the loop is highly conserved. To determine whether this region plays a role in fusion mediated by the HIV-1 envelope glycoproteins, we introduced seven single-amino-acid changes in the V3 loop. The mutant envelope glycoproteins were expressed from an HIV-1 envelope expression vector and analyzed for their ability to induce cell fusion in the absence of virus replication. Our results indicated that single-amino-acid changes in the V3 loop were capable of completely abolishing or greatly reducing the ability of the HIV-1 envelope glycoproteins to induce cell fusion, thereby identifying the V3 loop as a fusion domain of HIV-1. Mutations in the highly conserved tip of the loop or in a nonconserved region flanking the highly conserved tip had no effect on envelope glycoprotein synthesis, processing, transport, or binding to the CD4 receptor molecule. Mutation of the putative disulfide bridge-forming Cys at residue 336 blocked gp160 cleavage and CD4 binding.

Amino Acid Sequence↗
PubMed1991

A survey of cattle for antibodies against bluetongue and epizootic hemorrhagic disease of deer viruses in British Columbia and southwestern Alberta in 1987.

In 1987 a serological survey of cattle for antibodies (Ab) to bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) was undertaken in British Columbia and southwestern Alberta after infection with the viruses was diagnosed in wild and domestic ruminants in the Okanagan Valley. Of 4610 cattle tested, five had Ab only to BTV, 125 had antibodies only to EHDV and 16 had Ab to both viruses. The Ab were identified as specific for BTV type 11 (BT-11) or EHDV type 2 (EHDV-2). All but one of the seropositive cattle originated in the Okanagan Valley of British Columbia. The remaining one seropositive animal which had Ab to EHDV-2 was pastured with a bull purchased from the Okanagan Valley.

Alberta↗
PubMed1990

Hemorrhagic sequelae of immune thrombocytopenic purpura in human immunodeficiency virus-infected hemophiliacs.

Clinical bleeding tendency and tests of immune function were studied prospectively in 11 human immunodeficiency virus (HIV)-infected hemophiliacs with immune thrombocytopenic purpura (ITP) and a platelet count less than 50,000/microL. These 11 patients represented 13% of a well-characterized cohort of 87 HIV + hemophiliacs. ITP developed a mean 3.5 years after seroconversion, mean platelet count at presentation was 36,000/microL (range 15,000 to 49,000/microL), and the mean age at seroconversion was 37.1 years. Nine patients (82%) suffered bleeding complications, including four with intracranial hemorrhage, which was fatal in three. At the onset of ITP, five had AIDS and six were asymptomatic. Mean T4 lymphocyte count at onset of ITP was 126 +/- 32/microL (range 5 to 267/microL). Sustained treatment responses occurred with intravenous gammaglobulin (2 of 2), one of whom spontaneously remitted, and with zidovudine (1 of 2), but not with steroids (0 of 6) or danazol (0 of 3). In conclusion, 13% of a cohort of HIV + hemophiliacs has developed ITP with platelets less than 50,000/microL, a significant proportion of whom (82%) have experienced bleeding complications. It is recommended that treatment for ITP in HIV + hemophiliacs be instituted once the platelet count falls below 50,000/microL in order to avoid serious hemorrhagic sequelae.

Adolescent↗
PubMed1990

Characterization of the fusion domain of the human immunodeficiency virus type 1 envelope glycoprotein gp41.

The human immunodeficiency virus transmembrane glycoprotein gp41 has at its amino terminus a strongly hydrophobic stretch of 28 amino acids flanked by a highly conserved series of polar amino acids. To investigate the role in syncytium formation of the hydrophobic amino terminus of gp41 and the polar border of this hydrophobic region, we introduced eight single-amino acid substitutions and one double-amino acid substitution in the amino-terminal 31 amino acids of gp41. The mutant envelope glycoproteins were expressed from two distinct human immunodeficiency virus type 1 envelope glycoprotein expression vectors; the effects of the mutations on syncytium formation, envelope glycoprotein transport, secretion, and CD4 receptor-binding were analyzed. Results showed that polar substitutions throughout the hydrophobic amino terminus of gp41 greatly reduced or blocked syncytium formation mediated by the human immunodeficiency virus type 1 envelope glycoproteins, as did nonconservative mutations in the polar border of the hydrophobic amino terminus. Mutations at gp41 amino acids 15, 26, and 29 also significantly increased the extent of gp120 secretion into the extracellular medium. None of the mutations detectably affected envelope glycoprotein processing or envelope glycoprotein binding to CD4.

Amino Acid Sequence↗
PubMed1989

Mutational analysis of the cleavage sequence of the human immunodeficiency virus type 1 envelope glycoprotein precursor gp160.

The envelope glycoproteins of the human immunodeficiency virus (HIV) type 1 are synthesized as a precursor molecule, gp160, which is cleaved to generate the two mature envelope glycoproteins, gp120 and gp41. The cleavage reaction, which is mediated by a host protease, occurs at a sequence highly conserved in retroviral envelope glycoprotein precursors. We have investigated the sequence requirements for this cleavage reaction by introducing four single-amino-acid changes into the glutamic acid-lysine-arginine sequence immediately amino terminal to the site of cleavage. We have also examined the effects of these mutations on the syncytium formation induced by HIV envelope glycoproteins. Our results indicate that a glutamic acid to glycine change at gp120 amino acid 516, a lysine to isoleucine change at amino acid 517, and an arginine to lysine change at amino acid 518 affect neither gp160 cleavage nor syncytium formation. The results obtained with the arginine to lysine change at amino acid 518 differ significantly from the results obtained with the same mutation at the envelope precursor cleavage site of a murine leukemia virus (E. O. Freed, and R. Risser, J. Virol. 61:2852-2856, 1987). An arginine to threonine mutation at gp120 amino acid 518, the terminal residue of gp120, abolishes both gp160 cleavage and syncytium formation. These findings demonstrate that despite its highly conserved nature, the basic pair of amino acids at the site of gp160 cleavage is not absolutely required for proper envelope glycoprotein processing. This report also supports the idea that cleavage of gp160 is required for activation of the HIV envelope fusion function.

Fluorescent Antibody Technique↗