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Biomedical subjects

C D Thomas

Publications and source records attributed to C D Thomas.

At least 19 recordsLinked to original sources
PubMed1997

Interlaboratory variation in oxygen tension measurement by Eppendorf "Histograph" and comparison with hypoxic marker.

BACKGROUND AND OBJECTIVES: The median of pO2 values in tumor measured by Eppendorf "Histograph" with a needle-type electrode has been used as a prognostic indicator in cancer patients. However, it is not established that a pretreatment measured pO2 value can be used as a universal predictor of local control probability, because the variation in pO2 values, especially in hypoxic tissue, among institutes may not allow comparison of measured "absolute pO2 values." The purpose of this study was to examine the variation in oxygen tension measurement by Eppendorf "Histograph" among six laboratories using a single batch of mice and tumors and the same detailed protocol. These results were also compared to the immunohistochemical staining of 2-nitromidazole adducts. METHODS: C3H mice bearing FSaII murine fibrosarcoma subcutaneously were shipped to all laboratories, and the oxygen status in tumors and in normal subcutis was examined using Eppendorf "Histograph" and immunohistochemical hypoxic marker. RESULTS: All laboratories showed that the FSaII tumor was hypoxic with at least 77% of measured points under 10 mmHg in pO2 and with a median pO2 value less than that of normal subcutis. These results were further confirmed immunohistochemically. These findings are interpreted as evidence that the pO2 values measured by Eppendorf "Histograph" can be useful. However, the median values of tumor pO2 varied from 1.5 mmHg to 5.6 mmHg among the laboratories, and pO2 of normal subcutis also varied from 28 mmHg to 38 mmHg. There were also significant differences in hypoxic fraction, defined as the fraction under a given oxygen partial pressure (i.e., under 2.5, 5, or 10 mmHg), among institutes. CONCLUSIONS: Caution needs to be exercised in using the absolute, median, or distribution of pO2 values measured by the Eppendorf "Histograph" to compare the data between laboratories or to predict the radiation response in an individual subject.

Animals↗
PubMed1997

Evaluation of sexual misconduct complaints: the Oregon Board of Medical Examiners, 1991 to 1995.

OBJECTIVE: In 1991 the Oregon Board of Medical Examiners initiated a separate category for the complaint of sexual misconduct. Investigated complaints of sexual misconduct brought to the Oregon Board of Medical Examiners were analyzed for the years 1991 to 1995 to serve as a baseline. Comparison was made to the Federation of State Medical Boards sexual misconduct data for 1991 and 1992. STUDY DESIGN: One hundred complaints brought against 80 licensees were evaluated by practitioner's degree, age group, sex, specialty, and disposition of complaints for the years 1991 to 1995. The allegations were classified into behavior categories of sexual impropriety, sexual transgression, and sexual violations. RESULTS: Sexual misconduct was the allegation in 5.9% of the complaints investigated for the study period. Oregon had more sexual misconduct complaints than the average reported to the Federation of State Medical Boards for the years 1991 and 1992. Most (72%) complaints came from the patients or their families. Two female physicians (2.4%) had sexual boundary complaints. Sexual misconduct complaints increased by a risk ratio of 1.44 with advancing age by decades. Allegations classified into behavior categories according to severity revealed 39% sexual impropriety, 31% sexual transgression, and 30% sexual violation. Reportable disciplinary actions occurred only with multiple allegations of sexual impropriety (6.5%) and for sexual transgression (27%) whereas sexual violation allegations often had one complainant but there were 54% reportable disciplinary actions. Family practice, obstetrics and gynecology, and psychiatry had the highest incidence of sexual misconduct complaints whereas psychiatry and obstetrics and gynecology had the highest incidence of reportable disciplinary actions. Twenty-five percent of the closed cases resulted in reportable disciplinary actions. This analysis is discussed in relationship to legal and ethical issues and the goal of zero tolerance. CONCLUSIONS: Oregon has a higher percentage of sexual misconduct complaints than the average for 42 states reporting to the Federation of State Medical Boards for the years 1991 and 1992. Analysis of the Oregon Board's experience for the study years will provide a baseline for future evaluation and as an educational resource for the Oregon Board of Medical Examiners and professional and specialty societies. Ethical standards, the reporting and investigative processes, and the legal framework are in place and lessen the incidence of sexual misconduct and work toward zero tolerance.

Adult↗
PubMed1996

Age trends in remodeling of the femoral midshaft differ between the sexes.

Cross-sectional area properties of the femoral midshaft from 203 individuals of known height and weight. 1-97 years of age, from a modern Australian population were quantified using automatic video image analysis. The aim of this study, taking height and weight into account, was to determine whether (a) age trends in remodeling differ between the sexes, (b) men are better able to compensate for bone loss with age, and (c) this protective mechanism is carried through into old age. Our findings indicated that during adulthood there are distinct gender differences in femoral remodeling. From around the third to the seventh decade, men showed a fairly uniform increase in subperiosteal area, polar moment of inertia, and medullary area. Women displayed two distinct phases during this period: relative stability until around the menopause and then a marked increase in all of the above variables. In old age, gender differences diminished, both sexes showing reduced periosteal apposition and increased endosteal resorption. The resultant decline in cortical area of approximately 4% in men and 15% in women from the third to the eighth decade was significant only in women. For a given height, men had larger, stiffer femoral shafts with a greater cortical width and area and maintained this advantage into old age. Diaphyseal bone was not immune from age-related changes affecting other skeletal sites: however, due to compensatory remodeling, which was particularly evident in men, this was not reflected in increased fracture rates.

Adolescent↗
PubMed1996

Bone feature analysis using image processing techniques.

In order to establish the correlation between bone structure and age, and information about age-related bone changes, it is necessary to study microstructural features of human bone. Traditionally, in bone biology and forensic science, the analysis if bone cross-sections has been carried out manually. Such a process is known to be slow, inefficient and prone to human error. Consequently, the results obtained so far have been unreliable. In this paper we present a new approach to quantitative analysis of cross-sections of human bones using digital image processing techniques. We demonstrate that such a system is able to extract various bone features consistently and is capable of providing more reliable data and statistics for bones. Consequently, we will be able to correlate features of bone microstructure with age and possibly also with age related bone diseases such as osteoporosis. The development of knowledge-based computer vision-systems for automated bone image analysis can now be considered feasible.

Adult↗
PubMed1996

Transient perfusion and radiosensitizing effect after nicotinamide, carbogen, and perflubron emulsion administration.

In order to improve the effect of radiation on tumour response, nicotinamide, perflubron emulsion and carbogen were administered which act on both diffusion limited hypoxia and intermittent perfusion limited hypoxia. These treatments were used in different combinations. The maximal radiosensitizing effect was found with the combination of the three treatments. The aim of this study was to use a double staining method (Hoechst 33342 and DiOC7(3) to evaluate the influence of nicotinamide, perflubron emulsion and carbogen on transient perfusion in three tumour cell lines transplanted onto nude mice: one rodent (EMT6), two human (HRT18, a rectal adenocarcinoma; and Na11+, a melanoma). For untreated groups, the percentage of closed and mismatched vessels depended on the tumour cell line. Carbogen alone or carbogen plus perflubron emulsion decreased the number of mismatched and closed vessels only for the two human cell lines. Nicotinamide was effective in decreasing the percentage of mismatched and closed vessels only for the melanoma cell line. The combination of nicotinamide, carbogen and perflubron emulsion was the most effective at decreasing both percentage of mismatched and closed vessels in all three tumours studies. This combination was also the most effective at enhancing the radiation response in all three tumours.

Adenocarcinoma↗
PubMed1996

Influence of melanin on pO2 measurement in vitro and in vivo.

In a previous study an apparent discrepancy was found between the radiobiological hypoxic fraction of tumours and the tumour oxygenation: the lowest percentage of low pO2 values was observed in the most hypoxic tumour, a heavily pigmented melanoma Na11+. This report describes a similar study with two other less pigmented melanomas. The influence of melanin on pO2 readings was also studied using synthetic melanin and L-tyrosine. Tumour oxygenation was measured using the KIMOC 6650 histograph, apparent pO2 was also measured in the calibration chamber in a buffer containing melanin or L-Tyr at three pHs (6.5, 7.0, 7.5) and bubbled with three different oxygen concentrations (0.2, 2.0, 20.9%). The proportion of hypoxic cells, measured by an in vivo/in vitro colony assay, was 58% for Na11+, 30% for Be11 and 51% for Ma11 tumours. The melanin content (microgram/10(6) cells) was 6.5 (Na11+), 2.0 (Be11), and 4.3 (Ma11). The percentages of radiobiologically hypoxic cells and low pO2 reading values (<2 mmHg) were inversely correlated, contrary to what was expected. In buffer, the pO2 values increased significantly with the melanin concentration: the lower the oxygen concentration, the greater was the increase in pO2. The pO2 readings values increased to a lesser extent with L-Tyr concentration. These results indicate that clinical determination of pO2 in melanoma tumours requires careful attention.

Animals↗
PubMed1996

Regional fat placement in physically fit males and changes with weight loss.

The abdomen is the principal site of fat deposition in men, and because abdominal fat is readily mobilized during exercise, the relative proportion of fat in the abdominal site may negatively correlate with the amount of regular physical activity, and even with physical fitness. This study presents data for regional fatness in 165 fit young men (U.S. Army Ranger candidates; initial body fat = 14.7 +/- 4.7%) assessed by dual-energy x-ray absorptiometry (DEXA), and for relative changes occurring following a 13% weight loss produced by a 1000 kcal.d-1 energy deficit over 8 wk. Fat-free mass was constant across quintiles of percent body fat; only fat mass was different (16.2 +/- 2.2 kg and 6.0 +/- 1.4 kg at upper and lower quintiles, respectively). Truncal fat accounted for about 41% of total body fat in all quintiles; only the proportion of fat distributed to the arms was significantly higher in the fattest quintiles of men. Among a group of less intensely trained soldiers with the same average fatness as the highest quintile of Ranger students (20%), relative fat distribution to the trunk approached 50% of the total fat. Following weight loss, Ranger students lost half of the fat in all regions assessed (legs, arms, and trunk). The only significant association between regional losses and initial fatness was a greater proportion of fat lost from the arms in the fattest Rangers. These data suggest a "fit fat" distribution in active young men in which fat remains in the arms and legs until extreme weight loss occurs and the metabolically more active abdominal fat approaches depletion.

Absorptiometry, Photon↗
PubMed1995

Determination of sequence specificity between a plasmid replication initiator protein and the origin of replication.

Staphylococcal plasmids of the pT181 family replicate by a rolling circle mechanism, requiring the activities of a plasmid-specified Rep protein. The initiation event involves site-specific phosphodiester bond cleavage by Rep within the replication origin, ori. In vitro the Rep proteins also display type-I topoisomerase activity specific for this plasmid family. Although the single site of bond cleavage, ICR II, is conserved among all members of the pT181 family, the plasmid-specific Rep proteins are able to discriminate between family members in vivo, initiating replication only from the cognate origin. The basis of such specificity is believed to be due to a non-covalent binding interaction between Rep and a DNA sequence adjacent to the site of phosphodiester bond cleavage. Using the RepD protein specified by plasmid pC221, we present data for the physical parameters of RepD:oriD complex formation. Quantification of the relative strengths of the non-covalent interactions for different but related ori target sequences, measured by gel mobility shift experiments, has yielded data that are in accord with the known specificity of the protein in vivo. Oligonucleotide competition experiments demonstrate that this interaction is indeed attributable to the specificity determinant, ICR III. Protein-DNA crosslinking methods show that a carboxyl-terminal proteolytic fragment of RepD makes a specific interaction with the ICR III region of its cognate replication origin. Analysis of topoisomerase rates indicates that the interaction between ICR III and the carboxyl terminus of the protein is required before a productive interaction, namely the phosphodiester bond cleavage at the ICR II, can occur.

Bacterial Proteins↗
PubMed1995

A morphometric study of the cortex of the human femur from early childhood to advanced old age.

One hundred and ninety-five mid-shaft femoral bone samples were collected at the Victorian Institute of Forensic Pathology, Melbourne, Australia. These samples came from individuals aged 1-97 years, who had dies unexpectedly and were considered healthy immediately before death. From the samples, transverse sections 100-200 micronM thick were cut on a sawing microtome. Three groups of sections [from persons aged 19-21 (n = 9), 39-41 (n = 9), and 59-61 years (n = 9) at death] were adjusted to a thickness of 100 +/- 5 microns by hand-lapping and microradiographs were taken of these sections. Automatic image analysis methods were used to measure the area and perimeter of the femoral cortex for all 195 sections. Additionally, the number and areas of all holes within the cortex were measured for those sections that were microradiographed. The results show that, even though the number of Haversian canals measured from the entire bone cortex changes with age, the spread of values at any given age makes these measurements of limited value for age determination. From this it may be inferred that all methods that rely, to any extent, upon measurements of this parameter are likely to be flawed.

Adolescent↗
PubMed1995

Tumour oxygenation, radiosensitivity, and necrosis before and/or after nicotinamide, carbogen and perflubron emulsion administration.

Hypoxia is one of the factors involved in tumour resistance to radiotherapy. One way to improve tumour oxygenation is to use oxygen carriers such as perflubron emulsion plus carbogen or vasoactive drugs such as nicotinamide. The perflubron emulsion and carbogen act mainly on hypoxia caused by limited diffusion of oxygen; nicotinamide acts mainly on acute hypoxia. The aim was to correlate radiosensitivity and pO2 measurements (computerized pO2 histograph) after nicotinamide, perflubron emulsion and carbogen administration, and to determine the role of necrosis in this correlation. Two human tumour xenografts (HRT18, Na11 +) and one rodent tumour (EMT6) were used. Clonogenic assays and pO2 measurements were performed under similar conditions. The radiosensitization and oxygenation levels increased with all treatments. The maximal effects were found with the combination of nicotinamide (1 g/kg), perflubron emulsion and carbogen. A correlation between the radiosensitization and the pO2 measurements was found for the three cell lines with a cut-off point of 10 mmHg. The presence of necrosis could explain the low pO2 (< 2 mmHg) found even when complete radiosensitization was observed.

Animals↗
PubMed1994

Nicotinamide and carbogen: relationship between pO2 and radiosensitivity in three tumour lines.

The effects of carbogen breathing, nicotinamide injection and their combination on tumour radiosensitivity were correlated with changes in tumour O2 tension to determine the relationship between radiosensitivity and measured pO2. The radiosensitivity (in vivo-in vitro colony assay) and O2 tension (computerized pO2 histograph KIMOC 6650) of two human xenografted tumours (HRT18 and Na11+) and one murine tumour (EMT6) were measured under similar experimental conditions. A single dose of radiation was delivered (8 Gy for HRT18 and Na11+, 12 Gy for EMT6). Carbogen breathing, nicotinamide injection, and their combination all significantly increased radiosensitivity in the three cell lines (p < 0.05); the most efficient treatment was carbogen plus nicotinamide. The radiosensitization was optimum for EMT6 and Na11+. Mean and median pO2 increased with all three treatments, except for carbogen breathing in EMT6. Carbogen breathing had little effect on the proportion of low pO2 values, but induced pO2 values > 30 mmHg in all three tumour lines. Nicotinamide decreased the proportion of low pO2 values. This effect is larger with the combination carbogen plus nicotinamide. Almost all pO2 values < 2.5 mmHg were eliminated for HRT18 and EMT6. The relationship between radiosensitization and pO2 was significant when pO2 was expressed as the percentage of values below 7, 8, 9 and 10 mmHg for the three lines.

Animals↗
PubMed1994

Correlation between radiosensitivity, percentage hypoxic cells and pO2 measurements in one rodent and two human tumor xenografts.

Computerized pO2 histography has been used to measure the intratumor pO2 in patients for the past few years, and there is now evidence that these tumors contain hypoxic cells. One of the major questions that remains to be answered is the relevance of such data to radiosensitivity. The present study looks for a correlation between intratumor pO2, the percentage of hypoxic cells in the tumor and the radiosensitization induced by carbogen and/or the oxygen carrier, perflubron emulsion. Two human tumor xenografts (HRT18, Na11+) and one rodent tumor (EMT6) were used. The radiosensitivity (clonogenic assay) and the oxygen tension (computerized pO2 histography) were measured. All experiments were performed under similar conditions. Carbogen increased tumor radiosensitivity; sensitization was greatest when 4 ml/kg perflubron emulsion was used in conjunction with carbogen. The pO2 distribution was shifted to higher pO2 values in the tumors whatever the treatment; the shift was greater for perflubron emulsion plus carbogen. The low pO2 values (< 0.4 kPa) were lost for the HRT18 cells. A correlation (EMT6, HRT18) or a link (Na11+) between the radiosensitization and the oxygen tension measurements was found for values below 1.07 or 1.33 kPa. A trend between the percentage of hypoxic cells and pO2 measurements was found taking into account pO2 measurements comprised between 0.27 and 0.67 kPa.

Adenocarcinoma↗
PubMed1993

Controlled high-level expression of the lon gene of Escherichia coli allows overproduction of Lon protease.

Lon protease from Escherichia coli is an ATP-dependent protease which plays important roles in regulating the levels of specific proteins and in eliminating abnormal proteins. A major problem of working with Lon protease, the inability to substantially overproduce the enzyme, has been overcome by placing the lon gene under the control of an inducible trp promoter within a copy-number-controllable plasmid. Induction resulted in higher levels of production of the protease (approximately 100 micrograms/ml of cell culture) than were previously possible. The enzyme has been purified to apparent homogeneity and shown to possess the characteristic ATP-dependent proteolytic activity. Sequence verification during DNA manipulations revealed differences from two previously published sequences for the lon gene.

ATP-Dependent Proteases↗
PubMed1992

Nutrient balance and energy expenditure during ad libitum feeding of high-fat and high-carbohydrate diets in humans.

To study the influence of diet composition on regulation of body weight, we fed 21 weight-stable subjects (11 lean, 10 obese) high-carbohydrate (HC) and high-fat (HF) diets for 1 wk each. Although diet composition was fixed, total energy intake was unrestricted. Subjects had a higher energy intake on the HF (11,039 +/- 2700 kJ/d) than on the HC (10,672 +/- 2617 kJ/d) diet (P less than 0.05), but energy expenditure was not different between diets. On day 7 of the HC diet, carbohydrate (CHO) oxidation was significantly related to CHO intake with the slope of the regression line 0.99, suggesting that overall CHO balance was near zero. However, the slope of the regression line was greater for obese than for lean subjects. On day 7 of the HF diet, fat oxidation was significantly related to fat intake but the slope of the line was 0.50, suggesting that overall fat balance was positive. However, this relationship was due entirely to lean subjects, with obese subjects showing no relationship between fat intake and oxidation.

Adult↗
PubMed1991

Body-image marking. Validity of body-width estimates as operational measures of body image.

The relation of image-marking estimates of body width (IM) to actual widths, to other indices of body-size perception, and to measures of body satisfaction were examined using data obtained in a nonclinical sample of 200 women. The results of regression and correlational analyses were as follows: (a) actual widths accounted for only a small proportion of the variance in IM estimates, (b) the variance in IM estimates remaining after actual width was accounted for was not meaningfully related to other body-image indices, and (c) actual widths were more highly correlated with other body-image indices than were differences between estimated and actual widths (IM estimate-actual width). The current results suggest that most of the variance in IM estimates is error variance. Possible methodological confounds, which may bias women's estimates of body widths in the direction of overestimation, are discussed.

Adult↗
PubMed1991

Stable vs unstable weight history, body-image, and weight concern in women of average body weight.

The focus of this study was the effect of unstable weight history on current body-image among women. Participants were 45 college women of average weight (median age = 23 yr.); 15 had stable weight histories, 15 had past lowest weights 15% or more below current weight, and 15 had past highest weights 15% or more above current weight. The women were assessed on perceptual and attitudinal measures of body-image and a self-report measure of preoccupation with weight. In comparison to women with stable weight histories, those with unstable weight histories indicated greater dissatisfaction with the shape and size of their bodies, expressed more negative body attitudes, and reported increased concern about weight. Women with high weight histories overestimated their frontal body-size and expressed greater dissatisfaction with frontal size than women with low weight histories, but the two groups did not differ significantly on any of the other dependent measures. Possible explanations for increased body-image disturbance and weight concern among women with unstable weight histories are presented.

Adult↗
PubMed1991

Self-rated competence, current weight, and body-image among college women.

125 female undergraduates (M age = 19.7 yr.) self-rated their academic, social, and psychological competence and were assessed with respect to current weight, weight concern, and body attitudes. Self-rated academic, social, and psychological competence were not related to current weight; however, less positive self-evaluations of social competence were related to weight concern, negative appraisals of appearance, and dissatisfaction with body parts. Subjective ratings of academic and psychological competence were not significantly associated with any of these variables.

Achievement↗