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C D Thomas

Publications and source records attributed to C D Thomas.

At least 19 recordsLinked to original sources
PubMed1999

Plasmid replication initiator protein RepD increases the processivity of PcrA DNA helicase.

The replication initiator protein RepD encoded by the Staphylococcus chloramphenicol resistance plasmid pC221 stimulates the helicase activity of the Bacillus stearothermophilus PcrA DNA helicase in vitro. This stimulatory effect seems to be specific for PcrA and differs from the stimulatory effect of the Escherichia coli ribosomal protein L3. Whereas L3 stimulates the PcrA helicase activity by promoting co-operative PcrA binding onto its DNA substrate, RepD stimulates the PcrA helicase activity by increasing the processivity of the enzyme and enables PcrA to displace DNA from a nicked substrate. The implication of these results is that PcrA is the helicase recruited into the replisome by RepD during rolling circle replication of plasmids of the pT181 family.

Adenosine Triphosphatases↗
PubMed1999

Crystallization and preliminary X-ray crystallographic studies of RepDC, a hybrid rolling-circle plasmid replication initiator protein.

The hybrid plasmid-replication initiator protein RepDC, which is a fusion of the catalytic fragment of the RepD protein and the DNA-binding fragment of the RepC protein from Staphylococcus aureus, has been successfully crystallized and X-ray data to 3.5 A have been collected on a synchrotron radiation source. Crystals belong to space group I4132 with unit-cell dimensions a = b = c = 165.1 A. The crystals are estimated to contain one protein monomer per asymmetric unit, with 55% solvent content.

Bacterial Proteins↗
PubMed1999

Bone image segmentation.

Characteristics of microscopic structures in bone cross sections carry essential clues in age determination in forensic science and in the study of age-related bone developments and bone diseases. Analysis of bone cross sections represents a major area of research in bone biology. However, traditional approaches in bone biology have relied primarily on manual processes with very limited number of bone samples. As a consequence, it is difficult to reach reliable and consistent conclusions. In this paper we present an image processing system that uses microstructural and relational knowledge present in the bone cross section for bone image segmentation. This system automates the bone image analysis process and is able to produce reliable results based on quantitative measurements from a large number of bone images. As a result, using large databases of bone images to study the correlation between bone structural features and age-related bone developments becomes feasible.

Adolescent↗
PubMed1999

An automated analysis of intracortical porosity in human femoral bone across age.

The matrix of human cortical bone is arranged around a network of vascular spaces (hereafter referred to as "pores"). Our aim was to investigate age-related differences in human cortical porosity (total pore area divided by cortical bone area), pore size and number, and surface to volume ratios, while adjusting for sex, height, and weight. Ninety-six specimens of entire transverse sections of human femoral diaphysis, from subjects aged 21-92 years, were examined. We used our established automated image acquisition and analysis system which measures pores from entire sections of multiple specimens of bone. Over 400,000 pores were recorded. Results showed a greater porosity in older bone (p < 0.01) but marked variation in porosity for any given age. The cohort median, of the specimen medians, of pore cross-sectional area was 2050 microns 2. Older specimens did not have more pores than younger specimens but had a greater proportion of larger pores (p < 0.05) and greater intraspecimen variation in pore size (p < 0.001). The pore surface to bone matrix volume ratio was a median 2.3 mm2/mm3. This varied more than 4-fold between individuals but did not relate to age. No simple relationships were found between any of the measured parameters and either sex, height, or weight, even after adjustment for age. We conclude that the greater porosity in older specimens is due to greater pore size rather than a larger number of pores. Age, however, explains little of the inter-individual variation in the parameters studied.

Adult↗
PubMed1998

Bone size and mechanics at the femoral diaphysis across age and sex.

The reasons for the increase in fracture rates with age are not fully understood. It is known that there is a decrease in bone mass with a presumed loss of strength. This decrease may possibly be compensated for by changes in cross-sectional geometry. Previous studies, which have been limited by lack of information on subjects' heights and weights, were not able to resolve this issue. In this study, measurements of cross-sectional geometry (area and second moments of area) from 107 specimens of human femoral diaphysis from subjects aged 21-92 years were analysed. Mathematical models of the variation in bone geometry with age were developed. These models included the effects of sex, height and weight. Values of parameters from these models were then used in a biomechanical analysis of the static stresses at the mid-shaft of the femur. Results indicate that although there was a reduction in cortical area in old age, bone tissue was redistributed so that neither bending stresses in the coronal plane nor torsional stresses were higher in old age than in young adulthood. An additional finding was that at any age women had smaller bones, less cortical bone area and higher bone stresses than men. This finding may have some bearing on the higher fracture incidence seen in older women.

Adult↗
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↗
PubMed1997

Age-related changes in cortical porosity of the midshaft of the human femur.

Complete cross-sections from the femoral midshaft of 180 individuals of known height and weight, aged 21-97 y, from a modern Australian population were examined using automatic video image analysis to quantify total subperiosteal porosity (TSPP). More specifically, the aim was to investigate whether age changes were similar in both sexes in (1) total subperiosteal area (TSPA), cortical area (CA) and medullary area (MA), (2) intracortical porosity (ICP), and (3) the respective contributions to TSPP made by MA and intracortical void area (ICVA). Our findings indicated that both sexes showed a significantly greater height normalised TSPA in the 70s as compared with the 20s. Males had consistently larger bones with a greater height normalised CA. In both sexes CA showed a tendency to increase till the 7th decade and then to decline, more so in females. MA approximately trebled in females and doubled in males over the age range studied. Although ICP also increased, from 4-6% in young adults to over 9% in the elderly, it showed a significant difference between the sexes only in the 3rd decade, being greater in males at this stage. By contrast, TSPP became significantly greater in females (from that recorded in the 3rd decade) by the time they reached the 50s, while in males this did not occur till the 80s. It increased from approximately 25% in young adults of both sexes to approximately 50% in females and approximately 37% in males in their 80s. However, in the elderly there was great variability in both sexes in the appearance of bones from individuals of similar chronological age. Some bones differed little from those in younger subjects, others showed greatly increased ICP, still others displayed reduced cortical widths with low ICP. The femoral midshaft resembles other skeletal sites in that age changes in TSPP are more marked in females than males.

Adult↗
PubMed1997

Quantification of ethnic differences in facial profile.

The concept of facial aesthetics is becoming increasingly important and with the expanding application of orthodontic, orthognathic, plastic and reconstructive techniques to patients from continually diversifying ethnic backgrounds, it is timely that more elaborate methods for the evaluation of facial form are adopted. The aim of the present study was to further investigate the use of Fourier shape analysis in the quantification of facial profile and to investigate differences between racial groups. One hundred and twenty-two undergraduate dental students were photographed and surveyed for information pertaining to ethnic origin. Student's t-tests revealed significant differences (p < 0.05) in higher-order (fourth- and above) Fourier harmonics between male and female profiles, as well as between intervention and non-intervention groups. A comparison of multiple means test revealed significant differences (p < 0.05) in the third-order Fourier harmonic (vertex projection) between the Asian group and three other groups--Anglo-Celtic, Eastern European and Western European. Differences correlated with convexity in the lower third of the face, which was demonstrated by Fourier reconstruction.

Adolescent↗
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↗