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Biomedical subjects

T J Mason

Publications and source records attributed to T J Mason.

At least 55 records · Page 3Linked to original sources

Orthostatic hypotension following right ventricular myocardial infarction corrected with mineralocorticoid therapy.

Severe hypotension while standing became a problem in a patient after discharge from the hospital following right ventricular myocardial infarction. Hemodynamic studies showed that right ventricular systolic function did not maintain adequate left ventricular preload and that the patient did not compensate for cardiac dysfunction by increasing blood volume. Volume expansion by mineralocorticoid therapy corrected the orthostatic hypotension and ameliorated symptoms. Hypotension eventually resolved and therapy was stopped four months after the myocardial infarction.

Blood Volume↗

Effect of smoking and alcohol consumption on laryngeal cancer risk in coastal Texas.

Data from case-control studies of respiratory cancer conducted in the Texas Gulf Coast region between 1975 and 1980 were used to examine the effects of smoking and alcohol on laryngeal cancer risk. Analyses were limited to living white males, aged 30-79, which included 151 histologically confirmed incident laryngeal cancer cases and 235 population-based controls. A dose-dependent effect for cigarette smoking was observed, with odds ratios ranging from 4.4 for ever smoking up to one-half pack daily, to 10.4 for smoking more than two packs per day. Risks were strongest for current smokers and declined markedly following smoking cessation. Higher risks were associated with smoking nonfiltered than filtered cigarettes. No significantly elevated risks were associated with the use of other tobacco products. Odds ratios for alcohol beverages did not increase linearly with increasing use; instead risks were twofold for consumption of four or more drinks weekly. Patterns of risk associated with beer and hard liquor were not consistent and few participants drank wine. Although the data were sparse, a dose-response effect for alcohol intake was suggested for tumors of the supraglottis (n = 23), while for nonsupraglottic cases, alcohol risks were elevated but did not increase beyond those observed for four drinks per week. Predicted risks for the combined effects of cigarette and alcohol use were intermediate between an additive and multiplicative form of interaction.

Adult↗

Lung cancer in motor exhaust-related occupations.

The association between employment in motor exhaust-related occupations and the risk for lung cancer was examined in 2,291 male cases of lung cancer and 2,570 controls in data pooled from three U.S. case control studies carried out by the National Cancer Institute between 1976 and 1983. Most analyses were limited to subjects providing direct, in-person interviews, including 1,444 cases and 1,893 controls. For those providing direct interviews and employed 10 years or more in motor exhaust-related (MER) occupations, the age, smoking, and study area adjusted odds ratio (OR) for lung cancer was 1.5 (95% CI = 1.2-1.9). Risk was elevated for truck drivers (OR = 1.5; 95% CI = 1.1-1.9) and for other MER occupations (OR = 1.4; 95% CI = 1.1-2.0). The odds ratios associated with MER employment of 10+ years were 1.6 (95% CI = 1.2-2.1) for whites and 1.4 (95% CI = 0.9-2.1) for nonwhites; 1.2 (95% CI = 0.7-2.0) [corrected] for those with possible exposure to other recognized or reported lung carcinogens; and 1.6 (95% CI 1.2-2.1) for those without such exposure. The 50% excess risk for lung cancer associated with employment in motor exhaust-related occupations could not be explained by greater use of cigarettes or by other occupational exposures among these workers.

Aged↗

The new United States Cancer Atlas.

Published in 1975, the Atlas of Cancer Mortality for U.S. Counties: 1950-1969 proved useful in identifying geographic patterns, especially clusters of high-rate areas, that have stimulated further epidemiologic study of specific cancer sites. These data have been updated to include population and mortality statistics through 1980. Our new atlas presents static maps of area-specific mortality rates for each decade from 1950 to 1980 among white males and females for 33 cancer sites, along with dynamic maps illustrating the trends in these rates over time. Although the geographic distribution of mortality rates has become more uniform for most cancer sites, clusters of high-rate areas have persisted for several common tumors. However, some new patterns have appeared, notably the emergence of several high-rate areas for lung cancer among women. Possible explanations for the geographic peculiarities of cancer are considered, based on the results of correlation and analytic studies prompted by the earlier maps. These successive studies indicate the value of monitoring mortality statistics on a small-area scale as a strategy for generating etiologic clues and targeting epidemiologic research, although one must be mindful of geographic fluctuations in diagnostic and reporting practices, survival rates, and migration patterns.

Chronology as Topic↗

Serologically defined linear epitopes in the envelope protein of dengue 2 (Jamaica strain 1409).

Antisera from dengue patients and dengue virus infected rabbits recognized octapeptides corresponding to linear amino acid sequences in the envelope protein of dengue 2 (Jamaica 1409). Although no peptide was recognized by sera from all dengue infected hosts, two peptides (216LPLPWLPG223 and 448FSGVSWTM455) were recognized by sera from all dengue 2 infected rabbits. One of these 448FSGVSWTM455 was also recognized by sera from both the dengue 2 patients tested. No peptides were identified which reacted exclusively with all dengue 2 infected animals. Use of a mouse monoclonal antibody (1B7) enabled identification of two regions (50AKQPATLR57 and 127GKVVLPEN134) and possibly a third (349GRLITVNP356) in the envelope protein of dengue 2 likely to be involved in haemagglutination inhibition and virus neutralization in vitro.

Amino Acid Sequence↗

Similar binding properties of peptide ligands for a human immunoglobulin and its light chain dimer.

The urinary light chain dimer and serum monoclonal IgG1 protein from a patient (Mcg) with multiple myeloma and amyloidosis were systematically tested for their binding activities to peptides presented on solid supports. The system was validated using a series of enkephalins, beta-casomorphins and DNP-lysine derivatives which were known to complex with the dimer. Sets of peptide ligands binding to the proteins were constructed by incremental additions of amino acid residues to minimal binding units [Geysen et al., J. Immun. Meth. 102, 259-274 (1987)]. Both the amino acid sequences and the combinations of optical isomers were optimized at each stage of the syntheses. Binding could be demonstrated for ligands ranging in size from a tethered single amino acid to pentapeptides. At the dipeptide levels, the dimer and the IgG1 protein showed different preferences (Hp versus qf, where lower case letters designate D-amino acid residues). However, in a tetrapeptide ligand (qfHp) for the dimer, both of these initial preferences had converged. With few exceptions, the IgG1 molecule showed binding activity for the ligands developed for the dimer. Two sets of selected peptides, one based on Hp and the other on mW, were synthesized for diffusion into crystals of the dimer. X-ray analyses showed that these peptides bound exclusively in the main binding cavity between the "variable" domains of the dimer. As predicted from the ELISA results with tethered ligands, the relative occupancies in the crystals followed the order of tetrapeptide greater than tripeptide much greater than dipeptide. The crystallographic studies confirmed that peptides with very different sequences can bind in the same cavity.

Bence Jones Protein↗

Localization of virus-specific and group-specific epitopes of plant potyviruses by systematic immunochemical analysis of overlapping peptide fragments.

Virus-specific or group-specific antibody probes to potyviruses can be produced by targeting the immune response to the virus-specific, N-terminal region of the capsid protein (29-95 amino acids depending on the virus) or to the conserved core region (216 amino acids) of the capsid protein, respectively. Immunochemical analysis of overlapping, synthetic octapeptides covering the capsid protein of the Johnsongrass strain of Johnsongrass mosaic virus (JGMV-JG) has delineated the peptide sequences recognized by five polyclonal rabbit antisera and two mouse monoclonal antibodies (mAbs). The antibodies characterized were (i) three virus-specific rabbit polyclonal antisera and one virus-specific mouse mAb (1/25) raised against native virus particles, (ii) one polyclonal antiserum raised against trypsin-derived core particles of JGMV-JG, (iii) one group-specific polyclonal antiserum raised against the denatured, truncated coat protein from trypsin-derived core particles of JGMV-JG, and (iv) one group-specific mouse mAb (1/16) raised against native virus particles. The two epitopes seen by mAb 1/25 occurred at residues 18-27 and 43-52 and overlapped with the two major epitopes seen by the virus-specific polyclonal antiserum. The group-specific epitope seen in JGMV-JG by mAb 1/16 was also recognized strongly in potato virus Y, the type member of the potyvirus group. The multiple epitopes seen by the cross-reactive polyclonal antisera were distributed across the entire core region of the coat protein and their relative antibody binding responses varied between JGMV-JG, potato virus Y, and six other distinct potyviruses.

Amino Acid Sequence↗

Variation in smoking-related lung cancer risk among New Jersey women.

A population-based incident lung cancer case-control study was conducted among New Jersey women in 1982-1983. Interviews were completed for 994 cases and 995 controls. The association of lung cancer with cigarette smoking had an overall age-, race-, and respondent type-adjusted odds ratio of 8.5, with risks of 11.1, 62.6, and 3.9 for squamous cell, small cell, and adenocarcinoma, respectively. Analyses for squamous cell carcinoma showed significantly higher odds ratios for self-respondents than for subjects with next of kin respondents; this heterogeneity may be partially explained by misclassification in next of kin reports. Analyses for adenocarcinoma showed a significantly lower smoking-related risk among older women, which may be related to the later age at which these women began smoking. Analyses by histologic subtype showed lower risks for poorly differentiated squamous cell carcinoma and higher risks for poorly differentiated adenocarcinoma. This could be due to misclassification of histologic type and suggests that the actual smoking-related risk for squamous cell carcinoma might be higher than observed, and that for adenocarcinoma might be lower. Comparison of the results in this study with those from a similar study of lung cancer among men showed little difference between men and women in the magnitude of the association with smoking, or in the patterns of risk with intensity and duration.

Adenocarcinoma↗

Proportion of lung cancers in males, due to occupation, in different areas of the USA.

Occupational data from 5 case-control studies in the United States involving 2,973 male cases and 3,210 controls were analyzed to estimate the percentage of lung cancer attributable to well-known and suspected lung carcinogens. The studies were conducted in areas heterogeneous in terms of industrial activities. The percentage of lung cancers attributable to occupations entailing potential exposure to well-recognized carcinogens ranged, by study area, from 3 to 17%. The further inclusion of occupational groups with suspect carcinogenic exposures changed these estimates very little. Exclusion of data derived from next-of-kin interviews influenced the estimates of attributable risks, but not in a systematic fashion. The estimates also varied according to ethnic group, smoking status and birth cohort, with higher values in non-whites, non-smokers and among members of more recent birth cohorts. Possible errors in exposure classification, which may make these estimates conservative, are discussed.

Humans↗

Determinants of anterior mitral leaflet fluttering in pure aortic regurgitation from pulsed Doppler study of the early diastolic interaction between the regurgitant jet and mitral inflow.

Fluttering of the anterior mitral leaflet may be absent in patients with moderate to severe aortic regurgitation (AR), suggesting that the volumetric severity of AR alone does not determine the presence or absence of abnormal diastolic mitral valve motion. Fifteen patients with moderate to severe AR and normal mitral valves, 9 of whom demonstrated anterior mitral leaflet fluttering, were studied to elucidate the determinants of abnormal anterior mitral leaflet motion in these patients. Pulsed Doppler mapping of the flow-velocity disturbance of AR demonstrated its presence in the third of the left ventricular outflow tract adjacent to the anterior mitral leaflet in 8 of 9 patients with anterior mitral leaflet fluttering and none of the 6 patients without anterior mitral leaflet fluttering (p less than 0.02). The impact of this regurgitant jet on early diastolic transmitral inflow was examined with pulsed Doppler in these 2 groups of patients with AR and in age-matched control subjects. Deceleration of early diastolic transmitral filling was slower in patients with AR and anterior mitral leaflet fluttering than in age-matched control subjects (283 +/- 107 vs 457 +/- 176 cm/s2, p less than 0.02), whereas it was not significantly different from controls in AR patients without anterior mitral leaflet fluttering. This resulted in significant prolongation of the duration of early diastolic transmitral filling in patients with AR and anterior mitral leaflet fluttering (297 +/- 93 vs 203 +/- 44 ms for age-matched control subjects, p less than 0.02), which was not observed in patients with AR who did not have anterior mitral leaflet fluttering.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Occupational risk factors for laryngeal cancer on the Texas Gulf Coast.

Analyses are reported from a case-control interview study of incident laryngeal cancer on the Gulf Coast of Texas. Study subjects were 183 white men with squamous cell carcinoma of the larynx and 250 frequency matched controls. Occupational exposures were examined controlling for potential confounding by cigarette smoking and alcohol consumption. Significantly elevated risks were seen for men employed in the public services industry [transportation, communication, utilities, sanitary service; relative risk (RR), 1.6]; in metal fabricating (RR, 2.1), construction (RR, 1.7), and maintenance (RR, 2.7) occupations; and for workers potentially exposed to paint (RR, 1.8) and diesel or gasoline fumes (RR, 1.5). Elevated risks of border-line significance were seen for men employed as woodworkers/furniture makers (RR, 8.1) and for those with occupational exposure to asbestos (RR, 1.5). When asbestos was categorized by intensity of exposure, a significant positive gradient was found.

Alcohol Drinking↗

Cognitive features of continuous antigenic determinants.

We sought to identify the features controlling the specificity of antibody recognition and thus gain insights into molecular recognition between proteins in general. A total of 103 epitopes within 63 well-defined antigenic peptides homologous with the relevant antigen sequence were identified. The contribution of each amino acid residue to the antibody binding activity of each epitope was investigated by ELISA testing of complete sets of peptide analogs containing single amino acid replacements. The data are summarized in a replaceability matrix. Some of the high frequency replaceabilities were expected, such as aspartate for glutamate, serine for threonine, etc., but unexpected relationships were also found, such as a high degree of acceptability of methionine as a replacement. Replaceability with a residue of opposite charge was rare. Glycine and tyrosine were frequently of low acceptability, except for glycine as a replacement for alanine. It was found that on average only about four to five amino acid residues in epitopes were required to determine specificity and provide binding energy. Specificity and binding energy were attributed to amino acid side chains rather than main chain atoms. Propensity factors for occurrence of amino acids in antigenic determinants were calculated. The prominence of certain hydrophobic residues as residues critical to recognition by antibody suggests that the molecular surface of an antigen in its combined form with antibody is altered from that occurring in the absence of antibody. Thus, antigenicity is not a static surface phenomenon but depends on the ability of the antigen to undergo rearrangement, supporting the induced fit concept.

Amino Acids↗

Smoking and lung cancer: risk as a function of cigarette tar content.

The hypothesis of reduction in lung cancer risk associated with the adoption of low-tar cigarettes was examined in a subset of subjects from a population-based, case-control study of incident primary lung cancer among New Jersey white men. Risk was related to time-weighted average tar levels of cigarettes smoked in 1973-1980. Unadjusted estimates of risk were significantly low for the lowest tar (less than 14 mg/cig) smokers [odds ratio = 0.53 (0.29,0.97)] compared with the highest (21.1-28 mg/cig). However, adjustment by age and total pack-years rendered the risk reduction insignificant. Of note was the finding that cases who smoked low-tar cigarettes compensated for reducing tar by increasing the number of cigarettes they smoked by almost half a pack per day from the years 1963-1972 to 1973-1980, while in the same period controls and high-tar cigarette smoking cases did not increase the numbers smoked.

Humans↗

Carotene intake and the risk of laryngeal cancer in coastal Texas.

Between 1976 and 1980, data were collected for a case-comparison study of laryngeal cancer in white males aged 30-79 years in six Texas counties using all histologically confirmed incident cases and a population-based comparison group. Dietary interviews were obtained from 151 living cases and 178 living comparison subjects. A significant inverse association (odds ratio (OR) = 2.1) was found between low carotene intake and the risk of laryngeal cancer, but no association was found with total vitamin A or retinol intake. The inverse association with carotene intake was strongest among those who had stopped smoking 2-10 years before (OR = 5.9). The same risk for vitamin A intake was found by using a short list of foods based on contribution to variation in intake as was found by using a longer list based on per cent contribution to total intake. Definition of carotene as that which comes only from plant sources gives an estimate similar to a more complex method that takes into account carotene derived from both plant and animal sources.

Adult↗

Strategies for epitope analysis using peptide synthesis.

A recently developed approach to the synthesis and ELISA screening of large numbers of peptides is described. The method has created the opportunity to tackle questions about the sites and specificity of antigenic determinants which were formerly thought to be too difficult to answer. The various strategies for application of this method are described along with examples of their successful use. They include a procedure for locating all the continuous antigenic peptides of a protein antigen, and the identification of non-replaceable amino acid residues within an antigenic peptide. An approach to the determination of amino acid residues involved in the epitope for any monoclonal antibody is also described. These strategies open up the prospect of rapid mapping of the antigenic properties of hitherto poorly understood antigens.

Antibody Affinity↗

Chemistry of antibody binding to a protein.

The chemistry of antibody recognition was studied by mapping the antigenicity of the protein myohemerythrin with peptide homologs of the protein sequence. The results suggest that the entire protein surface is antigenic, but the probability of there being antibodies to a given site is influenced by local stereochemistry. Although accessible to an antibody binding domain, the least reactive positions cluster in the most tightly packed and least mobile regions and are closely associated with narrow, concave grooves in the molecular surface containing bound water molecules. The most frequently recognized sites form three-dimensional superassemblies characterized by high local mobility, convex surface shape, and often by negative electrostatic potential.

Antibodies↗

Seasonal variation in intake of carotenoids and vegetables and fruits among white men in New Jersey.

In a population-based case-control study of lung cancer among New Jersey men, usual adult consumption of many vegetables and fruits was included in the interview to assess the protective potential of carotenoids. With data from 900 controls the percentage of New Jersey white men who eat specific vegetables and fruits primarily in certain seasons, the relative importance of in-season and out-of-season consumption, and the median length of season were determined. Although first asking whether a food item was consumed all-year-round or primarily in certain seasons and then asking for the appropriate frequency of consumption facilitated the interview, obtaining out-of-season frequency of consumption and length of season was not necessary. Substituting 0 for reported out-of-season frequencies and 3 mo for reported season lengths reduced slightly the observed associations between diet and lung cancer risk but did not modify the overall pattern noted. Carotenoid intake in winter-fall was estimated to be about two-thirds that in summer-spring.

Adult↗

Statistically adjusted estimates of geographic mortality profiles.

The spatial variation of site-specific cancer mortality rates at the county or state economic area level can provide a) insights into possible etiologic factors and b) the basis for more detailed epidemiologic studies. One difficulty with such studies, especially for rare cancer types, is that unstable local area rate estimates, resulting from small population sizes, can obscure the underlying spatial pattern of disease risk. This paper presents a methodology for producing more stable rate estimates by statistically weighting the local area rate estimate toward the experience at the national level. The methodology is illustrated by the analysis of the spatial variation of two cancer types, bladder and lung, for U.S. white males over the three decades 1950-79.

Age Factors↗