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Biomedical subjects

D A Lawson

Publications and source records attributed to D A Lawson.

14 recordsLinked to original sources

Prostate stem cells and prostate cancer.

Understanding prostate stem cells (PSCs) may provide insight for the design of therapeutics for prostate cancer. We have developed a quantitative in vivo colony-forming assay and have demonstrated that the Sca-1 antigen is present on the surface of a prostate cell subpopulation that possesses multiple stem cell properties. Immunofluorescent analysis demonstrates that Sca-1 is expressed by both basal and luminal cells in the proximal region of the adult prostate, but is not expressed by either lineage in more distal regions. The proximal region has been suggested as the PSC niche based on BrdU label-retention studies and the presence of distinct smooth-muscle cells that produce high levels of TGF-beta. Sca-1 is also expressed by nearly all cells within fetal prostate epithelial chords, suggesting Sca-1 may be conserved on PSCs throughout development. Malignant epithelial cells from TRAMP mice, as well as normal prostate cells with lentiviral-mediated alteration of the PTEN/AKT signaling pathway, give rise to PIN lesions and prostate cancer in vivo. Alteration of PTEN/AKT signaling in Sca-1-enriched PSCs also results in PIN lesions, suggesting that PSCs can serve as one target for prostate carcinogenesis.

Animals↗

Prostate cancer screening--a physician survey in Missouri.

This study investigated prostate cancer screening practices using prostate specific antigen testing (PSA), digital rectal examination (DRE), and transrectal ultrasonography (TRUS) by primary care physicians in Missouri. In 1993, a mail survey was sent to a stratified random sample of 750 physicians whose primary specialty was general practice, family practice, or internal medicine. Three separate mailings resulted in an overall adjusted response rate of 60 percent. Ninety-five percent of physicians were more inclined to use PSA compared with three years previously, with only 45 percent of physicians more inclined to use DRE. An increase in the use of PSA following a negative DRE was reported by 85 percent and a greater inclination to use TRUS following a positive PSA was reported by 90 percent Eighty-six percent agreed with the American Cancer Society (ACS) guidelines on prostate cancer screening. Using logistic regression adjusted across levels of demographic and practice factors, prevalence odds ratios were derived with results indicating that agreement with ACS guidelines and being in private practice are strong predictors of a physician's inclination to routinely screen asymptomatic patients for prostate cancer. Our findings have provided baseline information on prostate cancer screening in Missouri and suggest that primary care physicians view PSA testing as a useful procedure and appear to be using it in a manner similar to the general pattern seen across the country.

Adult↗

Resting metabolic rate before exercise vs a control day.

Investigations on resting and recovery metabolism have used both preexercise and separate control-day measurements as a baseline for comparisons. The purpose of this study was to compare preexercise resting data with nonexercise control-day resting data. Seven active men aged 25 +/- 5 y and weighing 83.2 +/- 15.4 kg followed prescribed dietary (12-h fast) and activity (48-h abstinence) preparatory protocols and were scheduled to exercise for 60 min on three separate occasions. A fourth session involved no exercise (control) and included an extended rest period. Resting metabolic rate (RMR) and heart rate measured in a semirecumbent position were not significantly different among preexercise and control conditions. Respiratory exchange ratio (RER) increased as the control rest was extended to 120 min. Reliabilities for both RMR and RER were initially high but were decreased at the end of the extended rest. These results suggest that preexercise RMR data can be used as a baseline for comparison purposes. In addition, prolonging the rest period does not appear to improve the RMR or RER values.

Adult↗

Physiological and psychological responses to eccentric exercise.

In order to compare the physiological and psychological responses to various levels of eccentric exercise, 7 active men (25 +/- 5 yrs) exercised for 60 min on separate days at 60% of apparatus specific VO2 max using downhill jogging (-5% 60DH), level jogging (60J), and cycling (60C). Virtually all of the responses to 60DH fell between 60J and 60C. Heart rate, O2 pulse, and respiratory exchange ratio were significantly different among modes, with the responses during 60DH falling between those during 60J and 60C. Fat energy expenditure during the 60-min exercise bout was significantly higher during 60J, followed by 60DH and then 60C. Ratings of perceived exertion followed the order of 60C > 60DH > 60J. Vigor and fatigue scores on the Profile of Mood States also followed a hierarchy that paralleled the physiological responses. These results suggest that downhill jogging elicits physiological and psychological responses that are between those elicited by level jogging and cycling.

Adult↗

Prolonged recovery from eccentric versus concentric exercise.

In order to determine whether exercise mode affects recovery energy expenditure, 7 active men (average age 25 yrs) performed a control rest and three submaximal exercise bouts in counterbalanced order in separate weeks. The bouts, designed to involve three levels of eccentric muscular activity, included 60% VO2max jog (60 J), 60% downhill (-5%) jog (60 DH), 60% cycling (60 C), and a control session. Following a 24-hr period of regulated activity and diet, subjects exercised for 60 min. VO2 and RER were assessed during 48 hrs of regulated recovery. Total energy use was elevated following 60 C and 60 DH versus control, and fat energy use was elevated following 60 J, 60 DH, and 60 C versus control. For combined trials, the total energy use was higher at 1, 2, and 9 hrs postexercise. These results do not support the hypothesis that eccentric muscular activity affects the magnitude of recovery energy expenditure.

Adult↗

Biochemical characterization of Porphyromonas (Bacteroides) gingivalis collagenase.

A protease was purified from Porphyromonas gingivalis 1101, a clinical isolate, by sequential sodium dodecyl sulfate-polyacrylamide gel electrophoresis, substrate diffusion gel electrophoresis, and electroelution. The enzyme cleaved radiolabeled human basement membrane type IV collagen and the synthetic collagen peptide substrate for eukaryotic collagenases. It was inactivated by the thiol protease inhibitor N-ethylmaleimide but not by EDTA or EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and activated by reducing agents such as beta-mercaptoethanol. The enzyme exists as an active precursor protein of molecular mass 94 kDa and undergoes proteolytic cleavage to 75-, 56-, and 19-kDa forms. Biotin-labeled collagen bound specifically to the 94-kDa form of the protein and to its cleavage products in ligand blots, suggesting a role for this enzyme not only in collagen degradation but also in adhesion to collagenous substrata.

Cell Fractionation↗

Molecular analysis of periodontal pathogens.

Both Bacteroides gingivalis and Actinobacillus actinomycetemcomitans have been implicated in the destruction of periodontal tissues. To understand better the role putative virulence factors from the two bacterial species may play in an infection, the collagenase gene from Bact. gingivalis and the leucotoxin gene from A. actinomycetemcomitans were cloned. As it is intended to generate strains carrying defined mutations in these genes for in vitro and in vivo experiments, extensive restriction mapping and sequence analyses of these clones are being undertaken. Furthermore a conjugation system for Bact. gingivalis and A. actinomycetemcomitans will be established.

Actinobacillus↗

Identification of a potential protective microfilarial antigen from Litomosoides carinii (Nematoda, Filarioidea).

The proteins of the filarial parasite Litomosoides carinii that are presented to the host in the course of a natural infection were assessed by surface and intrinsic labelling, microfilarial agglutination assays and ELISA. Surface labelling revealed several proteins present on all parasite stages which were recognised by infected animals. Only one major surface protein of 55 KD was found on microfilariae, while in all other stages (adult males, adult females and infective larvae isolated from pool animals) a range of proteins could be labelled. Immunisation with live microfilariae obtained from blood provoked sera which agglutinated microfilariae in vitro and co-precipitated the 55 KD surface protein. A proportion of animals quantitatively infected with 30 infective larvae (L3) developed antibodies during prepatency that were capable of agglutinating microfilariae, suggesting a common epitope between L3/L4 and microfilariae. Intrinsic labelling of microfilarial proteins was used to identify three additional proteins of 16, 29 and 43 KD which may also be important during infection. The anti-microfilarial antibody titre was quantified by ELISA using microfilarial antigen and sera from various time points during the course of a natural infection.

Agglutination Tests↗

Observations on the applicability of the Wartenberg pendulum test to healthy, elderly subjects.

Wartenberg developed his pendulum test as a simple but precise test to assist examination of muscle tone in patients with Parkinson's disease. It has recently been reintroduced, and computerised, to evaluate spasticity in young hemiplegics. The results are reported on the highly successful application of this computerised test to large numbers of healthy, elderly subjects. The data have provided normal values for a number of measurements. Analysis of variance has shown that differences between individual subjects account for a major part of the total variabilities seen in all measurements taken. Factors such as position, leg and time trend contribute very little to total variation and, for practical purposes, can be ignored.

Adult↗

Does the Wartenberg pendulum test differentiate quantitatively between spasticity and rigidity? A study in elderly stroke and Parkinsonian patients.

The results of applying the Wartenberg pendulum test to the assessment of muscle tone in populations of stroke and Parkinsonian patients are described. The test was able to distinguish between increased muscle tone of the spastic or rigid type. The Parkinsonian patients showed a marked reduction of the maximum velocity of the leg swing, with the relaxation index tending to a value of about one. In contrast the affected limb of stroke patients showed a lesser reduction of the velocity of the swing, the relaxation index tending to a value of less than one.

Aged↗

The changing pattern of toxicity of digoxin.

Toxicity to digoxin was monitored in 437 consecutive recipients in a comprehensive drug surveillance programme, Adverse reactions developed in 19.5% and, in contrast to previous reports, were generally of a relatively benign nature. There were no drug-related deaths, but patients with adverse reactions spent longer in hospital. Low body weight, impaired renal function, old age and concurrent use of diuretics individually did not increase the risk of toxicity. This was attributed to improvements in the prescribing of digoxin. There was a highly significant excess of gastrointestinal reactions in women, which tended to occur early in the course of therapy. This susceptibility is not widely recognized. The use of loading doses may have caused many early reactions and it is suggested that this practice cold be abandoned in all but the most urgent cases.

Age Factors↗

Rotator cuff repair in a district hospital setting: outcomes and analysis of prognostic factors.

In a prospective study of 58 complete rotator cuff tears, 54 patients underwent surgery by a single surgeon for chronic, symptomatic, full-thickness rotator cuff defects. An independent observer performed the evaluation. Fifty-two of 58 patients reported marked relief of pain and rated themselves as having mild or no deficit in their ability to perform daily activities. The study evaluated preoperative and intraoperative factors that influenced postoperative outcome. Eighty-three percent of patients had good or excellent results according to the modified Constant scoring system and 76% with the UCLA system. There was no pain or minimal pain in 90%, and 92% reported overall improvement after the surgery. It is concluded that in a patient with a full-thickness rotator cuff tear, pain and shoulder function can be improved by acromioplasty and cuff repair, but a slight decrease in the range of motion and muscle strength will probably remain.

Activities of Daily Living↗

Stability of paraspinal tissue compliance in normal subjects.

OBJECTIVE: The following studies were performed in order to evaluate the stability of paraspinal tissue compliance measurements. Tissue compliance is a measure of the consistency or firmness of soft tissue and is determined by a hand-held tissue compliance meter. DESIGN: Descriptive and blinded time course intervention measurements. SETTING: All measurements were performed on subjects placed in the prone position on flat tables in a laboratory setting. PARTICIPANTS: Forty asymptomatic volunteer subjects. INTERVENTION: Tissue compliance measurements of the T6 and L3 paraspinal regions. MAIN OUTCOME MEASURE: Tissue compliance measurements recorded as millimeters of penetration of a metered probe. RESULTS: Data from this study indicate that paraspinal tissue compliance at the T6 and L3 regions does not change significantly over a 10-min interval, is not effected by the testing intervention and the number of abnormal left/right tissue compliance asymmetries is appropriate (5%) for a normal population of subjects. CONCLUSIONS: These findings tend to support the utility of tissue compliance as a possible tool for the evaluation of paraspinal soft tissue.

Chiropractic↗