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Biomedical subjects

P W Brandt-Rauf

Publications and source records attributed to P W Brandt-Rauf.

At least 91 records · Page 5Linked to original sources
PubMed1989

Serum oncogene proteins in hazardous-waste workers.

Oncogene protein detection may be a valuable molecular epidemiological marker of commitment to the carcinogenic pathway in worker populations exposed to carcinogens. This paper reports the use of serum immunoblotting with monoclonal antibodies to oncogene proteins to screen hazardous waste workers with potential carcinogen exposure who employ state-of-the-art work practices and personal protective equipment to minimize real exposures. Two individuals in this cohort were found to be trace positive for the ras oncogene protein in their serum, but this may have been due to their cigarette smoking. These results are contrasted to previous results in hazardous waste workers with real workplace carcinogen exposures.

Adult↗
PubMed1989

Ethical conflict in the practice of occupational medicine.

The practice of occupational medicine has been portrayed as being fraught with ethical conflict and yet this problem has received little systematic study. A question and case study survey of a randomly selected cohort of members of the American Occupational Medical Association has been performed to examine the extent and nature of this problem in occupational medicine practice in the United States. The results indicate a strong reliance on traditional medical role models in responding to ethical conflict but with significant underlying tension between more deontological physician-patient approaches and more teleological public health approaches. These results have significant implications for the synthesis of bioethical theories based on a perceived complementarity of ethical reality, as well as suggesting important improvements in future occupational medicine training.

Adult↗
PubMed1989

Health hazards of firefighters: acute pulmonary effects after toxic exposures.

As part of an environmental monitoring and medical surveillance programme to evaluate potential health hazards from firefighting, complete baseline medical examinations were performed on a cohort of 77 firefighters. During a ten day study period, 37 follow up medical examinations were performed after exposure to fire to monitor any significant differences in pre-fire and post-fire physiological indices, including pulmonary function and blood counts and chemistries. For the group as a whole, no significant differences were found. For individuals not wearing respiratory protective equipment, however, statistically significant post-fire decrements in FEV1 and FVC were noted. These decrements were consistent with previously shown levels of exposure to pulmonary toxicants in this cohort. These results support the need for more extensive use of respiratory protective equipment by firefighters.

Cohort Studies↗
PubMed1988

Conformational effects of the substitution of Arg for Gly 13 in the ras oncogene-encoded P21 protein.

The effect of the substitution of Arg for Gly 13 on the structure of the transforming region decapeptide (Leu 6-Gly 15) of the ras oncogene encoded P21 protein has been investigated using conformational energy analysis. A human malignancy has been identified that contains a ras gene with a single mutation in the thirteenth codon such that the encoded protein would have Arg substituted for Gly at this position, and transfection of cells in culture with this gene results in malignant transformation. Conformational analysis demonstrates that the Arg 13 decapeptide adopts a conformation identical to that for other peptides with substitutions at position 13 (Asp 13, Val 13) from transforming proteins that is distinctively different from that for peptides (Gly 13, Ser 13) from normal, nontransforming proteins. This is found to be an indirect effect resulting from changes in the conformation of Gly 12 produced by substitutions at position 13. These results are consistent with recent analysis of crystallographic data of proteins on conformational preferences for glycine in tripeptide sequences.

Arginine↗
PubMed1988

Structure of the carboxyl terminus of the RAS gene-encoded P21 proteins.

The three-dimensional structures of the carboxyl-terminal regions of the P21 protein products of the human Harvey (Ha), Kirsten (KiA and KiB), and neuroblastoma (N) RAS oncogenes and various mutants have been determined by using conformational energy analysis. The carboxyl-terminal region of P21 has been strongly implicated in the binding of the protein to the inner surface of the plasma membrane without which the protein is inactive. The only invariant residue in this region is Cys-186, which is necessary for the post-translational addition of palmitic acid. The surrounding sequences of the active native proteins differ considerably. Nevertheless, certain amino acid substitutions in this region are known to eliminate membrane binding and protein activity, suggesting that there is a conserved common structural feature in this region in the native proteins that is disrupted in the mutant proteins. Conformational energy analysis shows that the four native P21 proteins have a common structure in the form of an alpha-helix for the terminal pentapeptide. A mutant, pBW277, that fails to bind to the membrane and is inactive cannot adopt an alpha-helical structure in this region because of a proline at position 188. Another mutant, pBW766, that retains membrane binding and activity, on the other hand, retains the preference for an alpha-helical conformation in the terminal pentapeptide. These findings suggest that, despite various amino acid sequences in this region, the carboxyl-terminal pentapeptides of the P21 proteins form a distinctive structural domain that must have an alpha-helical structure for membrane binding and intracellular activity.

Cell Membrane↗
PubMed1988

New markers for monitoring occupational cancer: the example of oncogene proteins.

Molecular epidemiology is making rapid strides in the area of biologic monitoring for occupational cancer. Approaches are being developed and applied at the level of internal dose indicators (eg, urinary mutagenicity), biologically effective dose indicators (eg, carcinogen adducts), and preclinical response indicators (eg, chromosomal alterations). However, significant questions remain to be answered before these markers can be applied on a wider basis. In particular, it remains unclear how these markers relate to the clinical outcome of significance, namely occupational cancer. Recent developments in the understanding of oncogenes and their protein products offer new opportunities for the molecular epidemiology of occupational cancer through the use of these markers which seem to be critically involved in the oncogenic process and closely related to disease outcome. Thus, for example, through the application of immunoblotting of urine or serum with monoclonal antibodies to various oncogene proteins in cohorts of workers with potential carcinogen exposure, it may be feasible to identify those individuals most at risk for the development of occupational cancer at a sufficiently early stage that the oncogenic process could be aborted.

Antibodies, Monoclonal↗
PubMed1988

Current and future needs for occupational medicine physicians in nonindustrial settings: a survey of multispecialty group medical practices and health maintenance organizations.

The provision of occupational health services by multispecialty group medical practices and health maintenance organizations has received relatively little attention to date. To address this issue, a mail questionnaire survey of a random sample of these organizations around the country was conducted. Particular attention was focused on the current use of and future need for occupational medicine physicians and occupational health nurses in these settings. Results from the sample respondents indicate that these sites are playing a significant and increasing role in the provision of occupational health services with a projected approximate three-fold increase in the number of positions for occupational health professionals in these settings over the next decade. Assuming that these results are reflective of the situation nationwide, it is unlikely that the demand for these professionals will be met by current levels of graduate training.

Group Practice↗
PubMed1988

Serum screening for oncogene proteins in workers exposed to PCBs.

A cohort of 16 municipal workers engaged in cleaning oil from old transformers was examined for possible health effects from exposure to polychlorinated biphenyls (PCBs). In addition to the evaluation of routine clinical parameters (history, physical examination, liver function tests, serum triglycerides, serum PCB values), a new screening technique for the presence of oncogene proteins in serum using monoclonal antibodies was used to ascertain the potential carcinogenic risk from exposure in these workers. Except for one individual, serum PCB concentrations were found to be relatively low in this cohort, probably due to the observance of appropriate protective precautions. The results of liver function test were within normal limits and serum triglyceride concentrations showed no consistent relation to PCB concentrations. Six individuals, all of whom were smokers, showed abnormal banding patterns for fes oncogene related proteins. The individual with the highest serum PCB concentration also exhibited significantly raised levels of the H-ras oncogene related P21 protein in his serum. These oncogene protein findings may be indicative of an increased risk for the development of malignant disease in these individuals.

Adult↗
PubMed1988

Health hazards of fire fighters: exposure assessment.

There is growing concern over the detrimental health effects to firefighters produced by exposure to combustion byproducts of burning materials. To assess the types and levels of exposure encountered by firefighters during their routine occupational duties, members of the Buffalo Fire Department were monitored during firefighting activities with personal, portable, ambient environmental sampling devices. The results indicate that firefighters are frequently exposed to significant concentrations of hazardous materials including carbon monoxide, benzene, sulphur dioxide, hydrogen cyanide, aldehydes, hydrogen chloride, dichlorofluoromethane, and particulates. Furthermore, in many cases of the worst exposure to these materials respiratory protective equipment was not used owing to the visual impression of low smoke intensity, and thus these levels represent actual direct exposure of the firefighters. Many of these materials have been implicated in the production of cardiovascular, respiratory, or neoplastic diseases, which may provide an explanation for the alleged increased risk for these illnesses among firefighters.

Air Pollutants, Occupational↗
PubMed1987

Reaction of (bromoacetamido)nucleoside affinity labels with ribonuclease A: evidence for steric control of reaction specificity and alkylation rate.

Four new bromoacetamido pyrimidine nucleosides have been synthesized and are affinity labels for the active site of bovine pancreatic ribonuclease A (RNase A). All bind reversibly to the enzyme and react covalently with it, resulting in inactivation. The binding constants Kb and the first-order decomposition rate constants k3 have been determined for each derivative. They are the following: 3'-(bromoacetamido)-3'-deoxyuridine, Kb = 0.062 M, k3 = 3.3 X 10(-4) s-1; 2'-(bromoacetamido)-2'-deoxyxylofuranosyluracil, Kb = 0.18 M, k3 = 1700 X 10(-4) s-1; 3'-(bromoacetamido)-3'-deoxyarabinofuranosyluracil, Kb = 0.038 M, k3 = 6.6 X 10(-4) s-1; and 3'-(bromoacetamido)-3'-deoxythymidine, Kb = 0.094 M, k3 = 2.7 X 10(-4) s-1. 3'-(Bromoacetamido)-3'-deoxyuridine reacts exclusively with the histidine-119 residue, giving 70% of a monoalkylated product substituted at N-1, 14% of a monoalkylated derivative substituted at N-3, and 16% of a dialkylated species substituted at both N-1 and N-3. Both 2'-(bromoacetamido)-2'-deoxyxylofuranosyluracil and 3'-(bromoacetamido)-3'-deoxyarabinofuranosyluracil react with absolute specificity at N-3 of the histidine-12 residue. 3'-(Bromoacetamido)-3'-deoxythymidine alkylates histidines-12 and -119. The major product formed in 57% yield is substituted at N-3 of histidine-12. A monoalkylated derivative, 8% yield, is substituted at N-1 of histidine-119. A disubstituted species is formed in 14% yield and is alkylated at both N-3 of histidine-12 and N-1 of histidine-119. A specific interaction of the "down" 2'-OH group, unique to 3'-(bromoacetamido)-3'-deoxyuridine, serves to orient the 3'-bromoacetamido residue close to the imidazole ring of histidine-119. The 2'-OH group of 3',5'-dinucleoside phosphate substrates may serve a similar role in the catalytic mechanism, allowing histidine-119 to protonate the leaving group in the transphosphorylation step. (Bromoacetamido)nucleosides are bound in the active site of RNase A in a variety of distinct conformations which are responsible for the different specificities and alkylation rates.

Acetamides↗
PubMed1987

Conformational effects of substituting amino acids for glutamine-61 on the central transforming region of the P21 proteins.

The low-energy conformations for a series of peptides based on the sequence of the ras P21 protein from position 55 to position 67 have been computed using conformational energy analysis. These sequences differed at position 61 and contained Gln, Pro, Leu, Lys, and Arg at this position. P21 proteins with Gln, Glu, or Pro at this position do not cause cell transformation at normal levels of expression; proteins with substitutions of at least 14 other amino acids at this position (Leu, Lys, and Arg having been found in tumors in place of the normally occurring Gln-61) do cause malignant transformation of cells in culture. We find that the segments of residues 55-67 from the nontransforming proteins (Gln- or Pro-61) adopt a structure that is energetically unfavorable for the same segment with Leu, Lys, or Arg at position 61. The critical feature of this structure is an alpha-helix from residues 62 to 68. Residue 61 (Gln or Pro) adopts an extended conformation. On the other hand, the segment from transforming proteins can adopt two structures, one all alpha-helical from residue 61 to residue 68 and the other a less-regular, higher-energy structure. The segments from the normal protein can adopt the all alpha-helical structure, a finding that can explain the fact that elevated intracellular levels of the normal protein also cause cell transformation. The results of the calculations suggest that specific changes in the structure of this region can account for the oncogenic effect of the proteins in which substitutions occur.

Amino Acid Sequence↗
PubMed1987

Infectious disease in Antarctica and its relation to aerospace medicine: a review.

In many aspects, an Antarctic Station provides parallels to the environments encountered in space exploration, particularly with reference to infectious disease. In both instances, small groups of people live in isolation for long periods of time in a functionally sterile atmosphere. Therefore, studies of infectious disease in Antarctica should provide important insights into the experiences to be expected in spaceflight. This paper presents a summary of the information on the infectious and immunologic aspects of isolation derived over the years from research in Antarctica.

Antarctic Regions↗