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Biomedical subjects

J M Peters

Publications and source records attributed to J M Peters.

At least 19 recordsLinked to original sources

DDT and related compounds and risk of pancreatic cancer.

BACKGROUND: A cohort mortality study among 5886 chemical manufacturing workers was completed in 1987 and showed increased mortality due to pancreatic cancer. PURPOSE: We conducted a nested case-control study of pancreatic cancer among these chemical manufacturing workers to identify risk factors for this disease. METHODS: Twenty-eight verified cases of pancreatic cancer and 112 matched controls were studied. Next of kin of each subject were interviewed to determine lifestyle factors, including tobacco, alcohol, and coffee consumption. Written work records and interviews with co-workers were used to determine chemical exposures at the plant under study. RESULTS: DDT was associated with pancreatic cancer (risk ratio [RR] for ever exposed compared with never exposed = 4.8; 95% confidence interval = 1.3-17.6). Among subjects who had a mean exposure to DDT of 47 months, the risk was 7.4 times that among subjects with no exposure. Two DDT derivatives, Ethylan and DDD, were additionally associated with pancreatic cancer (RR = 5.0 and 4.3, respectively); exposures to these two chemicals were correlated, and it was not possible to determine whether each acted independently of the other. Smoking was identified as an independent risk factor, but controlling for smoking (and other potential confounders) in the analyses did not appreciably alter the risks seen for DDT, DDD, or Ethylan. CONCLUSIONS: Exposure to DDT was associated with pancreatic cancer. The association was not explained by exposure to lifestyle factors or other chemicals, and risk increased with both duration of exposure and latency since first exposure. IMPLICATIONS: These results may indicate that DDT can cause pancreatic cancer in humans under circumstances of heavy and prolonged exposure.

Case-Control Studies

Characterization of a cDNA clone from the haemoparasite Babesia bovis encoding a protein containing an "HMG-Box".

The complete nucleotide sequence of a Babesia bovis cDNA clone encoding a protein containing an HMG-Box has been determined. The predicted protein of 97 amino acids has a molecular weight of 11,116. It exhibits approximately 45% overall amino acid identity with the Saccharomyces cerevisiae non-histone protein 6A (NHP6A) and approximately 57% identity in the HMG-Box. The B. bovis protein has been designated NHP1. Like HNP6A, and unlike most other HMG1 homologues, NHP1 does not have a basic or an acidic carboxy-terminal domain. The amino acid sequence of HNP1 is much less similar to HMG1 homologues of another protozoan, Tetrahymena thermophila, than to the HMG1 homologues identified in S. cerevisiae, plants and vertebrates. This suggests that the T. thermophila proteins may not be true HMG1 homologues, or that they may be evolving at a much faster rate.

Amino Acid Sequence

Sequence of a putative glutathione synthetase II gene and flanking regions from Anaplasma centrale.

The complete nucleotide sequence of a putative glutathione synthetase gene (gsh II) has been determined from Anaplasma centrale. The predicted 308 amino acid protein has a molecular weight of 34,222 and is 32% identical to the enzyme, glutathione synthetase (EC 6.3.2.3), encoded by Escherichia coli gsh II. The previously proposed ATP-binding site is not highly conserved. The putative glutathione synthetase gene (gsh II) is preceded by an unassigned open reading frame. Downstream of gsh II is the 5' region of an open reading frame encoding a protein with significant similarity to bacterial D-alanine:D-alanine ligases (ADP forming) (EC 6.3.2.4). The predicted partial amino acid sequence is 33% identical to the amino acid sequence of the protein encoded by the E. coli ddl gene.

Adenosine Triphosphate

Ubiquitous soluble Mg(2+)-ATPase complex. A structural study.

We have performed a detailed structural analysis of the soluble Mg(2+)-ATPase complex purified from Xenopus laevis ovary, which is an abundant and ubiquitous homo-oligomeric protein complex located in the nucleus and in the cytoplasm, belonging to a novel multigene-family of putative Mg(2+)-ATPases. Enzyme activity staining after non-denaturing polyacrylamide gel electrophoresis revealed that Mg(2+)-ATPase activity of the native protein is dependent on oligomerization and could not be detected in dissociated subunits. For the native protein a sedimentation coefficient of 15.3 S and a corresponding relative molecular mass of 612,000 was determined by analytical ultracentrifugation and a relative molecular mass of 590,000 was estimated from scanning transmission electron microscopy, supporting our previous conclusion that the oligomer comprises six 97,000 Mr subunits. Conventional electron microscopy of negatively stained specimens revealed the Mg(2+)-ATPase complex to be a hexagonal molecule in its favoured "end-on" projection and a double-banded molecule in its "side-on" projection (approx. 12 nm diameter; approx. 9 nm height). In addition, dimerized complexes could be observed in negatively stained specimens, yielding pronounced hexameric images and four-banded images in their end-on and side-on orientations, respectively (approx. 12 nm diameter; approx. 18.5 nm height). Two-dimensional (2D = mono-molecular) crystals have been produced from the dimerized complexes by the negative staining carbon film technique. Hexagonal crystals with a p6 plane group symmetry were obtained from molecules in their end-on orientation and longitudinal arrays with a p2 symmetry from complexes in their side-on orientation. A low-resolution molecular model of the native protein, derived from averages of these two 2D crystals, is presented. From our results we propose oligomerization as an inherent structural principle of organization for this whole newly defined Mg(2+)-ATPase multigene-family, that includes such seemingly diverse functionally defined proteins as mammalian and yeast "vesicle fusion" and "peroxisome assembly" proteins and the product of the yeast cell cycle gene CDC48.

Animals

Occupational exposures and cancer of the colon and rectum.

The associations between occupational risks and colorectal cancer were examined in a Swedish population-based, case-referent study. The study was performed in Stockholm in 1986-1988 and included 569 cases and 512 referents. Relative risks (RRs) with 95% confidence intervals were calculated for different occupations/chemicals. Elevated risks of colon cancer were found among male petrol station/automobile repair workers (RR = 2.3, 0.8-6.6) and among males exposed to asbestos (RR = 1.8, 0.9-3.6), while elevated risks of rectal cancer were found among males exposed to soot (RR = 2.2, 1.1-4.3), asbestos (RR = 2.2, 1.0-4.7), cutting fluids/oils (RR = 2.1, 1.1-4.0), and combustion gases from coal/coke/wood (RR = 1.9, 1.0-3.7). However, due to a high correlation between the above-mentioned variables and the few exposed subjects, it is difficult to separate their effects properly. These analyses were adjusted for age. Further adjustments for diet, body mass, and physical activity had little or no influence on the results.

Adult

Cloning and characterisation of members of a family of Babesia bigemina antigen genes containing repeated sequences.

Bovine polyclonal antisera to Babesia bigemina antigens separated by phenyl-Sepharose chromatography were used to screen a B. bigemina lambda gt11 cDNA expression library. Eleven B. bigemina-specific cDNA clones were studied in detail. DNA sequencing of 2 representative clones identified open reading frames encoding polypeptides representing the carboxy-termini of 2 different proteins. Both polypeptides contained a related central motif of tandem repeats flanked by a highly conserved carboxy-terminal region, but the sequences preceding the repeats were not related. Hybridisation and restriction enzyme analysis of the cDNA clones indicated that they were derived from a family of at least nine related, but not identical genes. Four different members of the gene family have been isolated from a B. bigemina lambda EMBL3 genomic library. The genes are not closely linked and they occur on the largest and smallest B. bigemina chromosomes resolved by pulsed field gel electrophoresis (PFGE). Antibodies raised against the native antigens and purified on recombinant fusion proteins bound to multiple proteins (50-70 kDa) in the original B. bigemina antigenic fractions.

Amino Acid Sequence

Characterisation of genes encoding two novel members of the aldo-keto reductase superfamily.

The predicted amino acid sequence of the protein encoded by a cDNA clone isolated from the protozoan haemoparasite Babesia bovis has approximately 22% amino acid identity with the Pichia stipitis xylose reductase. There are similar levels of amino acid identity with other members of the aldo-keto reductase superfamily. The identities include many residues highly conserved in the superfamily. However, the amino acid sequence of the B. bovis protein (AKR1) clearly lies outside the cluster of the previously characterized members of the superfamily. A putative protein encoded by a previously undescribed partially characterized open reading frame at the igrA (increased glyphosate resistance) locus of Pseudomonas sp. strain PG2982 also exhibits similarity to AKR1 and the aldo-keto reductases.

Alcohol Oxidoreductases

Exposure to residential electric and magnetic fields and risk of childhood leukemia.

The relation between exposure to electric and magnetic fields in the home, as assessed by measurements, wiring configuration, and self-reported appliance use, and risk of leukemia was investigated in a case-control study among children from birth to age 10 years in Los Angeles County, California. Cases were ascertained through a population-based tumor registry from 1980 to 1987. Controls were drawn from friends and by random digit dialing. Interviews were obtained from 232 cases and 232 controls. Available for analysis were measurements of the magnetic field in the child's bedroom over 24 hours or longer (164 cases and 144 controls), spot measurements of magnetic and electric fields (140 cases and 109 controls), and wiring configuration (219 cases and 207 controls). No clear associations between leukemia risk and measured magnetic or electric fields were seen. An association between the Denver Wertheimer-Leeper wiring configuration and childhood leukemia risk was observed (odds ratio for very high relative to very low current and underground configuration combined = 2.15, 95% confidence interval 1.08-4.28; p for trend = 0.008) and was not substantially altered by adjustment for potential confounding factors. Cases were more likely than controls to report use of several appliances that produce high electric and magnetic fields. Our results support an association between childhood leukemia risk and wiring configuration, but not direct measurements of electric and magnetic fields.

Adult

Parental occupational exposures and risk of childhood cancer: a review.

We reviewed the literature in order to summarize the present knowledge on the association between parental occupational exposures to chemicals and the risk of childhood malignancy. The 32 studies pertaining to this topic were evaluated by considering various study qualities such as sample size, specificity of outcome, confounding, exposure specificity, and control selection. When evaluating the findings from any epidemiologic study, the potential sources of bias have to be considered. The selection of subjects, misclassification of exposure or outcome, and confounding from extraneous factors can contribute to a biased estimate of effect. Studies done to minimize these potential biases will be more valid, and these studies should be given the most weight when parental occupational exposures are evaluated as risk factors for childhood malignancy. We conclude that the preponderance of evidence supports the hypothesis that occupational exposure of parents to chemicals increases the risk of childhood malignancy. The parental occupational exposures implicated in childhood malignancy risk are exposure to chemicals including paints, petroleum products, solvents (especially chlorinated hydrocarbons) and pesticides, and exposure to metals. The available data do not allow the identification of specific etiologic agents within these categories of compounds. Future epidemiologic and toxicologic studies should be designed to pursue these leads.

Chemical Industry

Renal cell carcinoma among architects.

Data from a population-based cancer registry were analyzed according to occupation and industry at the time of diagnosis as part of a routine surveillance of the data for associations between occupation and cancer risk. A total of 119 cases of cancer of all sites were reported among architects between 1972-1986. From a total of 2,059 renal cell carcinomas in the registry, the 13 cases were observed among male architects, aged up to 64, 3.1 were expected. Significant elevations were not observed among other professional groups. Architects are exposed to several toxic and potentially carcinogenic chemicals. We suggest that investigators with cancer registry data coded according to occupation evaluate whether an association between employment as an architect and renal carcinoma exists in their data.

Adult

Occupational asbestos exposure and mesothelioma risk in Los Angeles County: application of an occupational hazard survey job-exposure matrix.

We evaluated the newly available National Institute for Occupational Safety and Health (NIOSH) National Occupational Hazard Survey (NOHS) job exposure matrix (JEM) by considering mesothelioma risk from asbestos exposure. We applied this system (NOHS-JEM) to the Los Angeles County Cancer Surveillance Program (CSP) to see how many cancer cases could be assigned asbestos exposure and how asbestos exposure affected mesothelioma risk. Using the same CSP data, our "experts" classified asbestos exposure simply by occupation and industry. Both exposure classifications were divided into low and high; the NOHS-JEM by the number of exposed people per couplet, and ours by judgements of intensity. Odds ratios (OR) for mesothelioma risk for low and high asbestos exposure for the NOHS-JEM were 2.0 (95% C.I. 1.2-3.4) and 2.5 (95% C.I. 1.2-4.8). For ours, corresponding risks were 1.6 (95% C.I. 1.1-2.4) and 6.3 (95% C.I. 2.5-15.1). Our system was able to assign more cases to couplets then the NOHS-JEM (35,895 to 22,369). Three limitations of the NOHS-JEM were that many occupation-industry couplets were not classified at all, many couplets associated with past asbestos exposure (before the 1972-1974 NOHS survey) were not classified as asbestos exposure, and no assessment of intensity was made. These limitations may apply to other exposures and should be carefully considered before the NOHS-JEM is applied to other case-control studies.

Adolescent

Astrocytoma risk related to job exposure to electric and magnetic fields.

To investigate the association between occupational exposure to low-frequency electric and magnetic (EM) fields and risk of brain tumors, a study was performed in Los Angeles County on 272 male adults with primary intracranial gliomas or meningiomas and 272 neighborhood controls. Complete occupational histories were collected. Risk associated with employment for more than 10 years in jobs that are presumed to entail exposure to EM fields was computed for various histological groupings. A nonsignificantly elevated risk of 1.7 was found for gliomas (all types pooled: 95% confidence interval 0.7-4.4), and a nonsignificantly reduced risk of 0.3 (95% confidence interval 0.03-3.2) was found for meningiomas. For astrocytomas, which form a subtype of the gliomas, a significantly elevated risk of 10.3 (95% confidence interval 1.3-80.8) was found; a significant upward trend (P = .01) of tumor incidence with increasing length of employment was observed. Most astrocytoma patients who worked in occupations involving exposure to EM fields were electricians or electrical engineers.

Adult

Child illness, the parenting alliance, and parenting stress.

Assessed relationship between children's minor illnesses during the first 3 years of life and parenting stress in the 4th year. Also examined whether a good parenting alliance would compensate for or moderate this relationship. Parents of 56 3- to 4-year-olds completed parenting alliance and stress questionnaires. Child morbidity, assessed from medical records, was directly related to mothers' but not fathers' feelings of stress. The parenting alliance was more strongly related to parenting stress for fathers than for mothers. However, child morbidity and parenting alliance interacted in predicting child-related paternal stresses. While fathers in a poor alliance reported more stress, stress was unrelated to their children's illnesses; for fathers in a moderate to strong alliance, illness and stress were positively correlated. Even minor child illnesses appear to be a source of stress for parents.

Acute Disease

Influence of short-term maternal zinc deficiency on the in vitro development of preimplantation mouse embryos.

In this study, we evaluated the use of mouse preimplantation embryos as a model to study zinc deficiency-induced abnormal development. In Experiment 1, the effect of culture medium Zn concentrations on blastocyst development was studied. Preimplantation embryos (2 and 4 cells) obtained from superovulated females developed normally in media containing 0.7-30 microM Zn for up to 72 hr; higher levels of medium Zn resulted in abnormal development. In Experiment 2A, females were fed diets containing 50 (+Zn) or 0.4 (-Zn) micrograms Zn/g (760 vs 6 nmol/g, respectively) from 1 day before to 1 day after mating (3 days total). Preimplantation embryos were removed from the dams and cultured for 72 hr in 0.7 microM Zn medium. Embryos from the -Zn dams were morphologically normal at time zero; however, over the 72-hr period, these embryos tended to develop at a slower rate than controls, although compaction and cavitation frequency were similar. By the end of the 72-hr culture period, embryos from -Zn dams had significantly fewer cells than did embryos from control dams. In Experiment 2B, an extended period of maternal Zn deprivation (6 days) was used to investigate the potential for further impairment of in vitro preimplantation embryo development observed in Experiment 2A. Results from this experiment were consistent with those from Experiment 2A, in addition to providing evidence that the developmental progress of embryos obtained from mice fed Zn-deficient diets for 6 days was significantly impaired. In Experiment 3, the potential for supplemental Zn in culture medium to overcome the impairment in development due to maternal Zn deficiency was investigated. Embryos from female mice subjected to the same dietary regimen described in Experiment 2A were cultured to the blastocyst stage in medium containing Zn at a concentration of either 0.7 or 7.7 microM. Medium Zn supplementation did not improve development of embryos from dams fed Zn-deficient diets. In summary, embryos from mice fed -Zn diets for a 3- or 6-day period encompassing oocyte maturation and fertilization exhibited impaired development in vitro. This impairment was not overcome by medium Zn supplementation.

Animals

Ultrastructure of the approximately 26S complex containing the approximately 20S cylinder particle (multicatalytic proteinase/proteasome).

We have isolated a large protein complex of approximately 26S from Xenopus laevis oocytes and eggs which is composed of the approximately 20S cylinder particle (multicatalytic proteinase/proteasome) and additional proteinaceous components. In its polypeptide composition and sedimentation coefficient this approximately 26S complex closely resembles the 26S ubiquitin-dependent protease, a high molecular weight multienzyme complex recently described in the literature. Specific antibodies directed against a single subunit of the approximately 20S cylinder particle retain, on affinity columns, the large approximately 26S complex, and on sucrose gradients up to approximately 50% of the approximately 20S cylinder particles present in oocyte extracts sedimented with approximately 26S, suggesting that a large proportion of the approximately 20S particles exists in the cell as a component of the approximately 26S complex. Electron microscopy reveals the approximately 26S complex to be a symmetrical elongated macromolecular assembly of at least three protein particles. The central core of the complex is formed by the approximately 20S cylinder particle to which two other large components are attached at the ends, yielding a dumbbell-shaped complex of approximately 40 nm in length. Dissociation of the approximately 26S complexes releases in addition to approximately 20S cylinder particles a novel type of a disc-shaped particle of approximately 15 nm diameter which may represent the attached components or subcomplexes of them. Based on its structural and biochemical properties we postulate that the approximately 26S complex identified here is identical to the ubiquitin-dependent protease.

Animals

An abundant and ubiquitous homo-oligomeric ring-shaped ATPase particle related to the putative vesicle fusion proteins Sec18p and NSF.

We have discovered a ring-shaped particle of 12.5 nm diameter, 14.5S and apparent molecular weight of approximately 570,000 that displays 6-fold radial symmetry and is composed of a single kind of an acidic (pI approximately 5.5) polypeptide of Mr 97,000 (p97). Using antibodies to this protein we have detected its occurrence in a wide range of cells and tissues of diverse species from frog to man, including highly specialized cells such as mammalian erythrocytes and spermatozoa. In Xenopus laevis oocytes, the particle is found in both isolated nuclei and in manually enucleated ooplasms, which corresponds to immunofluorescence staining dispersed over both nucleoplasm and cytoplasm. The particle has a N-ethylmaleimide (NEM)-inhibitable Mg2(+)-ATPase activity, and its amino acid sequence, as deduced from cDNA clones, displays considerable homology to the mammalian NEM-sensitive fusion protein (NSF) and yeast Sec18p believed to be essential for vesicle fusion in secretory processes, indicating that these three proteins belong to the same multigene family.

Adenosine Triphosphatases

Prognostic significance of the nuclear DNA content in localized prostatic adenocarcinoma.

The objective of this study was to determine if the nuclear DNA content could predict disease progression in patients with stage A or B prostatic cancer. The nuclear DNA content was determined by image analysis using Feulgen-stained nuclei in tissue sections of prostatic needle biopsies from 44 patients. The patients were followed for a mean of 69.5 months, during which 12 (17%) progressed to stage D2 disease (bone or soft tissue metastases). The average times to progression to stage D2 disease were 68 months for patients who initially had stage A2 disease, 47 months for stage B1 patients and 29 months for stage B2 patients. The DNA pattern was judged diploid or normal-range (Auer type I or II histogram) in 35 tumors (80%) and aneuploid (Auer type III or IV histogram) in 9 tumors (20%). Eight (89%) of 9 tumors with an aneuploid DNA pattern and 4 (11%) of 35 tumors with a normal-range or diploid DNA pattern progressed to stage D2 disease.

Adenocarcinoma