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Biomedical subjects

E S Johnson

Publications and source records attributed to E S Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Cancer mortality among workers in the meat department of supermarkets.

OBJECTIVES: The aim was to study the risk of dying from cancer among workers in the meat department of supermarkets potentially exposed to oncogenic retroviruses and fumes during the wrapping and labelling of meat. METHODS: Cancer mortality for the period 1949 to 1989 was compared in a previously studied cohort of 10,841 members of a local meatcutters' union in Baltimore, Maryland who worked in the meat department of supermarkets, after an extended follow up of nine years (1981-9). Person-years and deaths were apportioned in five-year intervals by sex, age, and calendar year, and standardised mortality ratio (SMR) and proportional mortality ratio (PMR) analyses were conducted. The United States general population was used as the comparison group. Analyses of SMR and PMR were also conducted for a control group of workers from the same union who worked exclusively in non-meat companies. RESULTS AND DISCUSSION: Among women, an SMR of 1.6 (95% confidence interval (95% CI) 1.1-2.2) and a PMR of 1.5 (95% CI 1.0-2.0) for lung cancer were found. For men, the SMR for cancer of the buccal cavity and pharynx was 1.8 (95% CI 1.0-3.0), and for colon cancer it was 1.5 (95% CI 1.1-2.1). The respective PMRs were 1.9 (95% CI 1.1-3.1) and 1.5 (95% CI 1.1-2.1). Whereas the role of non-occupational factors needs to be taken into account before occupational factors can be implicated in the occurrence of the excess of cancer of the buccal cavity and pharynx, and colon cancer in men, there is reason to suspect that occupational factors may be responsible for the lung cancer excess in women. Thus exposures that occur predominantly in women, such as exposure to fumes during wrapping and labelling, should be investigated as to their role in this excess.

Baltimore↗
PubMed1994

Poultry oncogenic retroviruses and humans.

Viruses of the avian leukosis/sarcoma group (ALSV) and reticuloendotheliosis viruses (REV) are highly prevalent in chickens and turkeys and naturally cause tumors in them. Commercial chickens are positive for antibodies, and a proportion actually carry infectious virus. Virus may be present in chicken products and in eggs, thus human exposure is virtually universal. The viruses show little potential for producing infectious viral particles in mammalian cells; nevertheless, they have the capacity to infect and transform mammalian cells (including human cells) in vitro, and to induce tumors in a variety of mammals, including primates. Most, but not all, of the serological studies in humans have been negative. Given the known behavior of these viruses in mammals, this was not unexpected. Moreover, there were methodological problems with most of the studies. There is some epidemiological evidence associating putative poultry exposure with cancer in humans. However, this has not been rigorously investigated. This paper is a comprehensive review of the extent of the carcinogenic potential these viruses show for humans. It is concluded, virological evidence indicates, that these viruses could conceivably have a carcinogenic potential for humans, but if so, at a level much less than in chickens. Whether this is insignificant, or translates to a real risk, is not known at the moment. Therefore, there is a need for definitive studies to completely rule out this possibility.

Alpharetrovirus↗
PubMed1993

Cancer incidence and mortality in women occupationally exposed to chlorophenoxy herbicides, chlorophenols, and dioxins.

The association between exposure to chlorophenoxy herbicides contaminated with dioxins and occurrence of cancer has been studied mainly in male populations. In animal experiments, gender differences have been recorded in the cancer response to administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mortality and cancer incidence in an international cohort of 701 women from an International Register of Workers occupationally exposed to chlorophenoxy herbicides, chlorophenols, and dioxins is examined. Cause-specific, national death rates and cancer incidence rates were used as referents. Cancer risk was not increased overall, with a standardized incidence ratio (SIR) of 96 and 95 percent confidence interval (CI) of 64-137, based on 29 cases. Among workers exposed to those chlorophenoxy herbicides contaminated with TCDD, excess cancer incidence (for all sites) was observed (SIR = 222, CI = 102-422, 9 cases); this was highest in the first 10 years after exposure. No excess was observed for breast cancer, the most common cancer in this cohort. Results on cancer mortality were consistent with those on incidence.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1993

The effects of 5-HT and m-chlorophenylpiperazine (m-CPP) on the efflux of [3H]-5-HT from human perfused platelets.

1. m-Chlorophenylpiperazine (m-CPP), a 5-HT1c-receptor agonist, induces migraine-like headaches when taken orally by migraine sufferers. The present study was undertaken to see what effects m-CPP had on 5-HT function in platelets. 2. Platelets from healthy male volunteers were loaded with [3H]-5-HT and continuously perfused in vitro with carboxygenated Krebs solution at 37 degrees C. After 30 min washout the effects of m-CPP, thrombin, 5-HT and ADP on the efflux of [3H]-5-HT were recorded. 3. m-CPP (0.5-500 microM) did not evoke an increase in the efflux of [3H]-5-HT over that occurring spontaneously whereas thrombin, unlabelled 5-HT and ADP did. The effects of 5-HT were potentiated by ADP. The results were identical whether or not the 5-HT reuptake blocker paroxetine (1 microM) was present. 4. m-CPP inhibited the increase in the efflux of [3H]-5-HT evoked by different concentrations of unlabelled 5-HT in the presence of ADP (2.5 microM) and displaced the 5-HT log concentration response curve to the right. A similar result was obtained with the 5-HT2-receptor antagonist ketanserin. 5. We conclude that m-CPP is a 5-HT2-receptor antagonist on human platelets, which is unlikely to account for its headache-inducing property, as many drugs effective in migraine prophylaxis have this action.

Adenosine Diphosphate↗
PubMed1993

Important aspects of the evidence for TCDD carcinogenicity in man.

Most of the evidence for the carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in humans has centered on whether TCDD causes soft-tissue sarcomas (STS) and malignant lymphomas (ML). Recently, reports from two of the largest occupational cohort studies have become available. A critical reappraisal of these and other recent reports indicates that it is unlikely that TCDD causes malignant lymphomas in humans. For STS, the evidence for an etiologic role for TCDD is not convincing. However, more data and further clarification are needed before a clear and objective evaluation can be made. Factors such as level of exposure, sex, and host susceptibility may be critical determinants of whether cancer occurs; there is evidence from both humans and animals that these factors play a role, and therefore these factors should be considered in future evaluations. There is a serious need to rule out the possibility that observed effects are due to other concomitant exposures. Consideration of the carcinogenic effects of TCDD in animals reveals consistency with the human data and points to other cancers such as those of the thyroid gland and lung, for example, which are more likely candidates for investigating the role of TCDD in their occurrence, while at the same time providing a basis for a better understanding and interpretation of the human data. There are now sufficient epidemiologic studies in place that will provide a better climate for a definitive evaluation in the near future.

Animals↗
PubMed1993

Glue-sniffing neuropathies.

The commonly used term for solvent abuse, glue sniffing, generally encompasses a variety of substances, including spray paint, thinners, nail varnish remover, gasoline, marking pens, and lighter fluids. Inhaled vapours eventually reach the lipids in the nervous system, where they can be stored for long periods. In three cases of glue-sniffing-related neurotoxicity, the peripheral nervous system was affected in two cases and predominantly the central nervous system in the third. Unfortunately follow up is difficult with this patient population and symptoms are often complicated by alcohol abuse.

Adolescent↗
PubMed1992

Current serum levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in phenoxy acid herbicide applicators and characterization of historical levels.

BACKGROUND: Workers who sprayed phenoxy acid herbicides, especially those who sprayed before 1975, may have been exposed to significant amounts of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent animal carcinogen present in herbicide preparations as a contaminant. PURPOSE: The aims of this study were (a) to determine serum levels of TCDD in a representative sample of workers occupationally exposed to the agent during the spraying of phenoxy acid herbicides; (b) to compare serum levels in workers exposed before 1965, when concentrations in herbicide products were unregulated and high, with levels in workers exposed after 1974, when concentrations were lower as a result of government regulations worldwide; and (c) to examine the correlation, if any, between serum levels and duration of employment in spraying. METHODS: Thirty-seven subjects were randomly selected from a group of 654 men who had sprayed the herbicides 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4-dichlorophenoxyacetic acid (2,4-D) in Australia for at least 12 months. The workers were classified as follows: eight who sprayed only before 1965, nine who sprayed only during the period after 1964 and before 1975, and 20 who sprayed during the period after 1974 and before 1991. Serum from the workers was analyzed for TCDD by high-resolution gas chromatography and high-resolution mass spectrometry at a detection limit of 0.6 parts per trillion (ppt) on a lipid-weight basis. In addition, rates of exposure to TCDD were estimated, as were TCDD serum concentrations at termination of employment and intensity of herbicide use. RESULTS: Only one worker, with a serum TCDD level of 34 ppt, had a serum level higher than the maximum level of 26 ppt reported for the general population. Assuming a half-life of 7.1 years, we estimated the mean exposure rates to be 2.7, 2.3, and 0.06 ppt/mo for the three epochs, respectively. We found the highest serum level of TCDD at the time of cessation of employment to be 329 ppt. Calendar period and intensity of use of 2,4,5-T and 2,4-D were statistically significant determinants of rate of exposure to TCDD, but 2,4-D was associated with exposure rate only for the pre-1975 periods. Estimated rates prior to 1965 were more than an order of magnitude higher than those after 1974. CONCLUSION: The highest estimated exposure rate was 20.7 ppt/mo, which suggests that some sprayers may have been exposed to levels comparable with those that produce cancer in laboratory animals.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1992

Perspectives on risk assessment impact of recent reports on benzene.

Very sensitive methods that can detect the benzene metabolite muconic acid (MA) in the urine of virtually all members of the general population have recently become available and have been used in a few occupational studies as a marker of benzene exposure. Preliminary findings from these studies suggest that urinary MA may be a reliable marker of occupational exposure to greater than 5 ppm benzene. It was also consistently observed that a certain proportion of the general population have urinary MA levels compatible with those seen in persons occupationally exposed to greater than 1 ppm benzene. It is unlikely that these elevated levels can be explained solely as being artifactual. The frequency with which they occur for a given individual, and the duration with which they are maintained, are not known. Information on these two factors is needed in order to adequately assess whether or not these levels present a significant risk for a segment of the general population.

Benzene↗
PubMed1992

Ubiquitin as a degradation signal.

For many short-lived eukaryotic proteins, conjugation to ubiquitin, yielding a multiubiquitin chain, is an obligatory pre-degradation step. The conjugated ubiquitin moieties function as a 'secondary' signal for degradation, in that their posttranslational coupling to a substrate protein is mediated by amino acid sequences of the substrate that act as a primary degradation signal. We report that the fusion protein ubiquitin--proline--beta-galactosidase (Ub-P-beta gal) is short-lived in the yeast Saccharomyces cerevisiae because its N-terminal ubiquitin moiety functions as an autonomous, primary degradation signal. This signal mediates the formation of a multiubiquitin chain linked to Lys48 of the N-terminal ubiquitin in Ub-P-beta gal. The degradation of Ub-P-beta gal is shown to require Ubc4, one of at least seven ubiquitin-conjugating enzymes in S.cerevisiae. Our findings provide the first direct evidence that a monoubiquitin moiety can function as an autonomous degradation signal. This generally applicable, cis-acting signal can be used to manipulate the in vivo half-lives of specific intracellular proteins.

Amino Acid Sequence↗
PubMed1992

Increasing radiation dose intensity using hyperfractionation in patients with malignant glioma. Final report of a prospective phase I-II dose response study.

We attempted to show a dose effect relationship for radiation therapy by treating patients harbouring malignant glioma with increasing doses of radiation in a step-wise fashion. We postulated that no increase in delayed toxicity would be seen because we used hyperfractionation technique. Between January 1981 and December 1988 we treated 280 patients three times daily at 4 hour intervals. 100 patients received a total dose of 6141 cGy, 73 patients received 7120 cGy, and 107 patients received 8000 cGy. CCNU was given at the time of tumor progression following radiotherapy. Median time to tumor progression was 28 weeks for patients who received 6141 cGy, 27 weeks for patients who received 7120 cGy and 36 weeks for patients who received 8000 cGy. Median survival was 46 weeks for patients who received 6141 cGy, 38 weeks for patients who received 7120 cGy and 45 weeks for patients who received 8000 cGy. There was no statistically significant difference in either time to tumor progression or survival among the three treatment arms and no dose response effect was seen. There was no increase in delayed radiation toxicity when the total radiation dose was increased up to 8000 cGy.

Adolescent↗
PubMed1991

Distribution and sampling of Aedes taeniorhynchus (Diptera: Culicidae) eggs in a Florida mangrove forest.

The distribution of Aedes taeniorhynchus (Wiedemann) eggs in a Florida mangrove basin forest was quantified and used to design a sampling plan. Eggs were found in detritus-rich soil with the highest densities in a band at elevations 0.1-0.2 m above the water line. Dispersion indices (k and Taylor's b) indicated that the eggs were aggregated; 14 of 16 populations tested fit the negative binomial distribution. A fixed-size sampling plan using systematic sampling was designed from these data.

Aedes↗
PubMed1991

Aedes taeniorhynchus (Diptera: Culicidae) oviposition patterns in a Florida mangrove forest.

The association of Aedes taeniorhynchus eggs and several variables was studied in a Florida mangrove forest. Eggs were limited to stands of red mangrove (Rhizophora mangle L.) that were embedded within a black mangrove (Avicennia germinans L.) forest. The occurrence of eggs was related significantly to elevation and the amount of detritus. Field and laboratory studies indicated that grazing on black mangrove detritus by the snail Melampus coffeus L. may have limited detritus accumulation and soil organic content, thus restricting mosquito oviposition to the red mangrove stands. Eggshells were concentrated in the same habitat as eggs, suggesting that eggshells may be used to identify oviposition patterns.

Aedes↗
PubMed1991

Human exposure to 2,3,7,8-TCDD and risk of cancer.

Most of the evidence for the carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in humans has centered around whether it causes malignant lymphomas (ML) and soft-tissue sarcomas (STS). A critical review of the literature indicates that the evidence does not support a causal role for TCDD in the etiology of ML. For STS, the evidence does not specifically incriminate TCDD either, although there is room for doubt. Cancers of other sites, particularly of the respiratory system and thyroid which were found to be statistically significantly in excess in either of the two largest studies of combined cohorts of occupationally exposed workers, were identified as candidate tumors for which a possible etiological role of TCDD might need investigation in future studies.

Case-Control Studies↗
PubMed1990

cis-trans recognition and subunit-specific degradation of short-lived proteins.

The N-end rule, a code that relates the metabolic stability of a protein to the identity of its amino-terminal residue, is universal in that different versions of the N-end rule operate in mammals, yeast and bacteria (unpublished data). The N-end rule-based degradation signal comprises a destabilizing amino-terminal residue and a specific internal lysine residue. We now show that, in a multisubunit protein, these two determinants can be located on different subunits and still target the protein for destruction. Moreover, in this case (trans recognition) only the subunit that bears the lysine determinant is actually degraded. Thus an oligomeric protein can contain both short-lived and long-lived subunits. These insights have functional and practical implications.

Amino Acid Sequence↗
PubMed1990

Association between soft tissue sarcomas, malignant lymphomas, and phenoxy herbicides/chlorophenols: evidence from occupational cohort studies.

Some case-control studies have reported a significant association between occupational use of phenoxy herbicides and chlorophenols and soft-tissue sarcomas and malignant lymphomas. However, persons who spray or apply these substances are concomitantly exposed to other potentially carcinogenic chemicals and oncogenic viruses, which have been found or suspected to play a role in the etiology of these tumors. No study has thoroughly controlled for these other exposures, some of which have been shown to be independently associated with these tumors even after controlling for exposure to phenoxy acids or chlorophenols. On the other hand, it has been found that an observed risk from exposure to phenoxy herbicides disappeared on controlling for some of these concomitant exposures in the rare instance this was attempted. Also, on several occasions, an association has been observed with occupations in which exposure to phenoxys and chlorophenols may occur, but not with the compounds themselves. Accordingly, a detailed review of the evidence from occupational cohort studies was conducted, to see if it corroborates that from case-control studies. It was found that the evidence does not unequivocally incriminate phenoxys and chlorophenols as a cause of these tumors. The results obtained with cohort studies of sprayers and applicators do not corroborate the association reported among this occupational group, in case-control studies. It is possible that the suspected association may well be due, partly or wholly, to one or more of the other concomitant exposures. However, in view of the fact that the majority of the cohorts need further follow-up to be informative, it is concluded that further studies of these cohorts are required before it can be determined whether or not these tumors are caused by exposure to phenoxy acids and chlorophenols.

Agriculture↗