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Biomedical subjects

I Calvert

Publications and source records attributed to I Calvert.

17 recordsLinked to original sources

Efficiency of different grouping schemes for dust exposure in the European carbon black respiratory morbidity study.

OBJECTIVES: The aim of this study was to assess the theoretical efficiencies of different grouping strategies and its effect on the exposure-response relation in a study of respiratory morbidity associated with exposure to total inhalable and respirable carbon black dust. METHODS: A large epidemiological study is being undertaken to investigate the respiratory health of employees in the European carbon black manufacturing industry in relation to exposure to carbon black dust. In phase 2 of the study, repeated measurements of total inhalable and respirable dust were taken which enabled estimation of various components of variability in the exposure data (within and between worker variance and within and between group variance). These variance components were used to calculate the contrast in exposure between the groups in various classification schemes and to calculate the theoretical attenuation of the exposure-response relation and the standard error (SE) of the slope. RESULTS: High contrast in exposure was found when workers were classified according to the combination of their factory and job category as well as when these combinations were amalgamated into five exposure groups. Attenuation was minimal with most grouping schemes; only with the individual based strategy was the attenuation large. The SE of the theoretically attenuated exposure-response slope was smallest for the strategy based on individual people followed by the classification scheme based on factory and job category. CONCLUSIONS: It was concluded that, although some assumptions for the calculations of the attenuation of the exposure-response slope were not met, the most appropriate classification scheme of the worker seems to be by the combination of factory and job category.

Carbon↗

Urinary 1-hydroxypyrene: a biomarker for polycyclic aromatic hydrocarbon exposure in coal liquefaction workers.

This study was undertaken to assess the suitability of urinary 1-hydroxypyrene (1-OHPyr) as a biological marker of polycyclic aromatic hydrocarbon (PAH) exposure in coal liquefaction workers. This is believed to be the first evaluation of the method in coal liquefaction workers. Ten workers were selected from a group of 30 workers considered likely to be at risk of contamination from PAHs by virtue of their jobs. Spot urine samples were collected at the start of a work period and at the end of each work shift, with analysis of 1-OHPyr being undertaken by high-performance liquid chromatography linked to a fluorescence detector. Exposure was assessed by the completion of questionnaires. Excretion of 1-OHPyr increased significantly over the working period, and there was a significant increase in 1-OHPyr where start-shift and end-shift samples were taken over one shift. A significant decrease in 1-OHPyr was found during breaks away from work.

Adult↗

Exposure to polycyclic aromatic hydrocarbons in coal liquefaction workers: impact of a workwear policy on excretion of urinary 1-hydroxypyrene.

OBJECTIVE: This study was undertaken to assess whether contaminated personal clothing worn beneath a coverall (normal workwear) is a source of potentially significant dermal exposure to polycyclic aromatic hydrocarbons (PAHs) in coal liquefaction workers. METHODS: An intervention study was conducted over a two week period involving 10 workers that reflected the range of activities performed at the factory. A cross over design was used to examine the influence of normal workwear (personal clothing worn beneath a coverall) and intervention workwear (new coverall, shirt, trousers, underwear, socks, and boots) upon excretion of urinary 1-hydroxypyrene (1-OHP) and skin pad deposition of pyrene. RESULTS: The impact of intervention was noted in three ways: (1) A notable reduction (55%) in the mass of 1-OHP excreted on the first day of the intervention phase was found. The median reduction in mass excreted (22.7 nmol) was significant from zero at the 5% level; (95% confidence interval (95% CI) 9.5-40.8 nmol). (2) A notable reduction (82%) in skin pad deposition of pyrene on the first day of the intervention phase was found. The median reduction of 13.20 ng.cm-2 was significant from zero at the 5% level; (95% CI 7.3-26.4 ng.cm-2). (3) About a 50% reduction in 1-OHP concentration over the working week occurred during the intervention phase; an increase of 2.07 mumol/mol creatinine was found from the start to the end of the work period during the intervention phase compared with an increase of 4.06 mumol/mol creatinine during the normal phase. This reduction was not significant at the 5% level. CONCLUSION: The results indicate that on the first day of the working week investigated, significant reductions in absorbtion (as measured by excretion of urinary 1-OHP) and deposition of PAHs (as measured by skin pad deposition of pyrene) can be effected by improvements in workwear policy. The impact of the improved workwear regimen was also detected by reduction in spot urinary 1-OHP concentrations, although this effect was less pronounced. One implication of the findings is that exposure to PAHs may arise from workers' own contaminated personal clothing. As a consequence of this study an improved workwear policy has been implemented at the factory.

Adult↗

Audiometry in industry.

Pure tone audiometry is the most common method of screening for hearing loss. The test itself is straightforward and the equipment readily available, so it forms part of the hearing conservation programmes of many industries. Whilst the test itself is straightforward, because of individual variability in response, interpretation of the results may be difficult. There has therefore been considerable debate on the role of audiometry in hearing conservation. The last official publication dealing with audiometry was a Health and Safety Executive discussion document 'Audiometry in Industry' published in 1978: no current recommendations are available. This article is a critical review of the advice given in that document, which aims to clarify the role that audiometry may play in the conservation of hearing. It was concluded that audiometry in the individual may perform poorly in strict cost benefit terms when used serially to detect a deterioration in hearing of an individual, but as the only form of biological monitoring it should be available to all employees who are advised to wear hearing protection at work. A distinction between audiometry in the individual and group audiometry is then made: the analysis of the hearing of a group may be useful in assessing risk to hearing. Graphical methods of analysis are shown, and more formal methods of statistical analysis discussed.

Audiometry, Pure-Tone↗

Neurobehavioral effects of long-term occupational exposure to organic solvents: two comparable studies.

Two comparable cross-sectional studies were carried out employing the same methodology but involving two separate solvent-exposed populations (N = 90, N = 144). In each study, solvent-exposed workers were compared with age-matched controls on tests selected from the Neurobehavioral Evaluation System and on standardized questionnaire measures of symptomatology and psychiatric state. A similar pattern of results was obtained in the two studies indicating a significant effect on cognitive functioning, after controlling for confounding variables, occurring in those with more than 30 years of exposure. A more specific effect on learning processes was observed in those with more than 10 years of exposure. There were no indications in either study of a solvent-related increase in psychiatric symptoms.

Adult↗

Negative regulation of human immunodeficiency virus type 1 expression in monocytes: role of the 65-kDa plus 50-kDa NF-kappa B dimer.

Although monocytic cells can provide a reservoir for viral production in vivo, their regulation of human immunodeficiency virus type 1 (HIV-1) transcription can be either latent, restricted, or productive. These differences in gene expression have not been molecularly defined. In THP-1 cells with restricted HIV expression, there is an absence of DNA-protein binding complex formation with the HIV-1 promoter-enhancer associated with markedly less viral RNA production. This absence of binding was localized to the NF-kappa B region of the HIV-1 enhancer; the 65-kDa plus 50-kDa NF-kappa B heterodimer was preferentially lost. Adding purified NF-kappa B protein to nuclear extracts from cells with restricted expression overcomes this lack of binding. In addition, treatment of these nuclear extracts with sodium deoxycholate restored their ability to form the heterodimer, suggesting the presence of an inhibitor of NF-kappa B activity. Furthermore, treatment of nuclear extracts from these cells that had restricted expression with lipopolysaccharide increased viral production and NF-kappa B activity. Antiserum specific for NF-kappa B binding proteins, but not c-rel-specific antiserum, disrupted heterodimer complex formation. Thus, both NF-kappa B-binding complexes are needed for optimal viral transcription. Binding of the 65-kDa plus 50-kDa heterodimer to the HIV-1 enhancer can be negatively regulated in monocytes, providing one mechanism restricting HIV-1 gene expression.

Base Sequence↗

Cloning and characterization of a novel sequence-specific DNA-binding protein recognizing the negative regulatory element (NRE) region of the HIV-1 long terminal repeat.

The present studies describe the isolation of a murine cDNA clone that encodes a novel DNA-binding protein recognizing the negative regulatory element (NRE) region of the HIV-1 long terminal repeat (LTR). This cDNA expresses a truncated protein with a functional DNA-binding domain, which is rich in glutamine/proline and serine/threonine, a characteristic of a majority of sequence-specific DNA-binding proteins and transcriptional factors. The cDNA hybridizes to a single-copy gene that is expressed as an approx. 4.2-kb mRNA in a variety of murine and human cell types, implying that this gene is expressed in an ubiquitous fashion. The NRE region has been reported to down-regulate LTR-directed gene expression [Rosen et al., Cell 41 (1985) 813-823]. This is the first sequence-specific DNA-binding protein reported to recognize the NRE region.

Amino Acid Sequence↗

Phosphorylation of human interleukin-2 (IL-2).

Human interleukin-2 (IL-2) is a lymphokine which is capable of activating lymphocytes and supporting the long-term in vitro growth of activated T cell clones. Recombinant human IL-2, expressed in either E. coli or cos cells, was shown to be phosphorylated by protein kinase C. Phosphorylated IL-2 synthesized in E. coli was analyzed by SDS-PAGE, reverse phase HPLC, and tryptic peptide mapping. The phosphorylated tryptic peptide was identified as the N-terminal fragment containing a single phosphorylation site at the serine residue at position 7. There was no difference in biological activity between non-phosphorylated and phosphorylated IL-2, as determined by a T cell growth assay. Although the physiological role of phosphorylation of IL-2 is unclear, IL-2 can be labeled with [gamma-32P] ATP and protein kinase C to a high specific radioactivity, and the synthesis of biologically active 32p-labeled IL-2 may be useful for receptor-binding studies of the cells containing low level of phosphoprotein phosphotases.

Amino Acid Sequence↗

Molecular cloning, sequence analysis and mRNA expression of human ADP-ribosylation factor.

The ADP-ribosylation factor (ARF) is the small (21 kb) GTP-binding protein required for the efficient cholera toxin-catalyzed ADP-ribosylation of purified Gs, the stimulating regulatory component of adenylate cyclase. Human ARF cDNA clones were obtained from a human cDNA library by cross-species hybridization with bovine ARF1, and the nucleotide and deduced amino acid sequences were determined. Comparison of the sequences of human and bovine ARF1 showed 90% identity at the nucleotide level and 100% identity at the amino acid level, demonstrating the highly conserved nature of the ARF protein. Using human ARF cDNA as the probe, we have detected ARF messenger RNA (approximately 2.2-2.3 kb) in a wide variety of human tissues and tumor cell lines.

ADP-Ribosylation Factor 1↗

Oligomerization of pregnancy-specific beta 1-glycoprotein (SP1) at physiologic pH and ionic strength.

Highly purified pregnancy-specific beta 1-glycoprotein (SP1) migrated in gel electrophoresis as a homogeneous species and behaved as a single species in 6 mol/l guanidinium chloride (GdmCl), both in the ultracentrifuge and HPLC. At physiologic pH and ionic strength, in the absence of GdmCl, SP1 existed in the form of oligomers of apparent molecular weights of 40 000 to greater than 300 000. The specific activity of these oligomers varied over a 5-fold range. Electrophoretic mobility also varied among SP1 oligomers, with increasing (alpha-like) mobility shown by oligomers of increasing molecular size. Oligomerization may explain some or all of the reports of SP1 heterogeneity.

Chromatography, High Pressure Liquid↗

Human chorionic gonadotropin and human placental lactogen in extragonadal tumors. An immunoperoxidase study of ten non-germ cell neoplasms.

The immunoperoxidase localization of the alpha and beta subunits of human chorionic gonadotropin (hCG) and of human placental lactogen (hPL) was studied in ten extragonadal nontrophoblastic tumors associated with raised serum levels of one or more of these placental proteins. Three of the tumors were bronchial carcinomas, one was a gastric carcinoma, two were malignant carcinoids (one bronchial and one gastric), two were pancreatic islet cell carcinomas, and two were metastatic carcinomas with an unknown primary site. The maximum alpha subunit serum level was 33,000 ng/ml (gastric carcinoid), the maximum hCG/hCG-beta level was 705,000 ng/ml, and the maximum hPL level was 50 ng/ml (both in the gastric carcinoma). An indirect immunoperoxidase technique and rabbit polyclonal affinity-purified antibodies and peroxidase conjugates were used on formalin-fixed, paraffin-embedded sections. Five blocks (eight cases) or six blocks (two cases) from various sites were obtained from each patient at surgery and/or autopsy. Positive stains for hCG/hCG-beta were seen in six of seven tumors (25/37 blocks) with raised levels, for the alpha subunit in nine of nine tumors (30/47 blocks), and for hPL in two of five tumors (4/26 blocks). Only a relatively minor number of the cells were positive, and within the same case, there was considerable site-to-site variation in the number of positive cells. Large bizarre cells contained hCG/hCG-beta as well as the alpha subunit, if it was demonstrated in the same tumor as the beta subunit. Otherwise, the alpha subunit was found in small unremarkable cells. Giant cells that were smaller than those positive for hCG/hCG-beta contained in hPL. In some serial sections, hCG-alpha, hCG/hCG-beta, and hPL were segregated in different cell populations, supporting the concepts of their separate genetic control.

Adenocarcinoma↗

Physicochemical studies of pregnancy-specific beta 1-glycoprotein: unusual ultracentrifugal and circular dichroic properties.

The molecular properties of native and modified pregnancy-specific beta 1-glycoprotein (SP1) from human placenta were evaluated by sedimentation equilibrium, gel electrophoresis, and circular dichroic measurements. Native SP1 contained 6.2% N-acetylneuraminic acid (NANA), 5.8% galactose (Gal), 13% N-acetylglucosamine, 6.5% mannose, and 1.1% fucose but no detectable N-acetylgalactosamine. Treatment with mixed exoglycosidases and alpha-mannosidase removed 79% of the carbohydrate including all of the NANA and Gal. The intensity of the circular dichroic spectrum of SP1 in the far ultraviolet was quite low with a positive maximum at 235 nm and a negative maximum at 215 nm. The 235-nm band was lost upon treatment with reducing agents or with guanidinium chloride (GdmCl), but not by treatment with neuraminidase. Treatment of SP1 with neuraminidase, or with mixed exoglycosidases and alpha-mannosidase, resulted in decreases of the apparent molecular weight obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Neither exposure of SP1 to GdmCl nor its reduction and alkylation resulted in the appearance of subunits on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The partial specific volume of SP1 determined experimentally by comparing sedimentation equilibrium profiles in H2O and D2O was 0.695 +/- 0.007 mL/g. The molecular weight of SP1 in 6 M GdmCl (in the presence or absence of reducing agents) by equilibrium sedimentation was 42 300 +/- 400. In the absence of denaturing agents, SP1 existed in the form of aggregates (at least as high as trimeric SP1) that dissociated only slowly upon dilution. The presence of these aggregates may contribute to the reported molecular heterogeneity of SP1.

Alkylation↗

Stimulation of N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate of ectopic production of the free beta subunit of chorionic gonadotropin by a human brain tumor cell line.

Previous studies have favored a basic difference in the regulation of specialized protein production by cells derived from the usual tissue of origin (eutopic) and cancer cells derived from a tissue not normally producing the protein (ectopic). Thus N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate was believed to stimulate only eutopic (but not ectopic) chorionic gonadotropin production, and butyrate to stimulate only ectopic (but not eutopic). However, in CBT, a human brain tumor cell line, we find that N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate, but not butyrate, stimulated ectopic production of the beta subunit of chorionic gonadotropin. We conclude that neither butyrate nor cyclic adenosine 3':5'-monophosphate derivatives reliably discriminate ectopic from eutopic regulation.

Brain Neoplasms↗

Increased "pregnancy-specific" beta1-glycoprotein in certain nonseminomatous germ cell tumors.

Schwangerschafts (pregnancy) protein No. 1 (SP1), a recently identified beta1-glycoprotein that occurs during pregnancy, was assayed in the sera of 97 men with germ cell tumors of the testis. SP1 was elevated at 11-440 ng/ml in 3 of 6 men with choriocarcinomas, in 5 of 17 men with teratomas or "teratocarcinomas" (embryonal carcinomas and teratomas), and in 5 of 50 men with embryonal carcinomas; the highest value in 143 patients with nonmalignant diseases was 9.1 ng/ml. None of 24 sera from men with seminomas and none of 5 sera from men with orchitis had elevated SP1. In the 1 patient examined, testicular choriocarcinoma SP1 had immunochemical and gel chromatographic properties similar to those of highly purified SP1 of placental origin.

Choriocarcinoma↗

Radioimmunoassay of "pregnancy-specific"-beta 1-glycoprotein (SP1).

A radioimmunoassay for SP1 ("pregnancy-specific" beta 1-glycoprotein) is described in which a sensitivity of 0.1 microgram/L was achieved by use of an antiserum with Ka approximately equal to 1.7 x 10(11) L/mol and delayed addition of a 125I-SP1 tracer (specific acty, 25 Ci/g) that was stable for use in the assay for at least six to seven weeks. We also report an additional anti-SP1 serum, from an early bleeding, that displayed "apparent positive cooperativity" in the IgG but not the IgM fraction.

Beta-Globulins↗