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Biomedical subjects

C Cooke

Publications and source records attributed to C Cooke.

At least 19 recordsLinked to original sources

Induction of apoptosis by pyrrolidinedithiocarbamate and N-acetylcysteine in vascular smooth muscle cells.

Pyrrolidinedithiocarbamate (PDTC) and N-acetylcysteine (NAC) have been used as antioxidants to prevent apoptosis in lymphocytes, neurons, and vascular endothelial cells. We report here that PDTC and NAC induce apoptosis in rat and human smooth muscle cells. In rat aortic smooth muscle cells, PDTC induced cell shrinkage, chromatin condensation, and DNA strand breaks consistent with apoptosis. In addition, overexpression of Bcl-2 suppressed vascular smooth muscle cell death caused by PDTC and NAC. The viability of rat aortic smooth muscle cells decreased within 3 h of treatment with PDTC and was reduced to 30% at 12 h. The effect of PDTC and NAC on smooth muscle cells was not species specific because PDTC and NAC both caused dose-dependent reductions in viability in rat and human aortic smooth muscle cells. In contrast, neither PDTC nor NAC reduced viability in human aortic endothelial cells. The use of antioxidants to induce apoptosis in vascular smooth muscle cells may help prevent their proliferation in arteriosclerotic lesions.

Acetylcysteine

The cap and the 3' splice site similarly affect polyadenylation efficiency.

The 5' cap of a mammalian pre-mRNA has been shown to interact with splicing components at the adjacent 5' splice site for processing of the first exon and the removal of the first intron (E. Izaurralde, J. Lewis, C. McGuigan, M. Jankowska, E. Darzynkiewicz, and I.W. Mattaj, Cell 78:657-668, 1994). Likewise, it has been shown that processing of the last exon and removal of the last intron involve interaction between splicing components at the 3' splice site and the polyadenylation complex at the polyadenylation signal (M. Niwa, S. D. Rose, and S.M. Berget, Genes Dev. 4:1552-1559, 1990; M. Niwa and S. M. Berget, Genes Dev. 5:2086-2095, 1991). These findings suggest that the cap provides a function in first exon processing which is similar to the function of the 3' splice site at last exon processing. To determine whether caps and 3' splice sites function similarly, we compared the effects of the cap and the 3' splice site on the in vitro utilization of the simian virus 40 late polyadenylation signal. We show that the presence of a m7GpppG cap, but not a cap analog, can positively affect the efficiency of polyadenylation of a polyadenylation-only substrate. Cap analogs do not stimulate polyadenylation because they fail to bind titratable cap-binding factors. The failure of cap analogs to stimulate polyadenylation can be overcome if a 3' splice site is present upstream of the polyadenylation signal. These data indicate that factors interacting with the cap or the 3' splice site function similarly to affect polyadenylation signal, along with m7GpppG cap, is inhibitory to polyadenylation. This finding suggests that the interaction between the cap-binding complexes and splicing components at the 5' splice site may form a complex which is inhibitory to further processing if splicing of an adjacent intron is not achieved.

Base Sequence

Airway structure and inflammatory cells in fatal attacks of asthma.

Fatal attacks of asthma usually occur against a background of chronic persistent symptoms, presumably due to chronic airway inflammation and changes in airway wall structure. Death from asthma is usually attributed to excessive airway narrowing due to a combination of muscle spasm and mucous plugging. To test the hypothesis that airway wall structure and/or the inflammatory cell profile are related to the duration of a fatal attack of asthma, inflammatory cell profiles and airway structure were examined in cases of fatal asthma and related to the duration of the fatal attack. In transverse sections of large and small airways from subjects dying from asthma, the numbers of eosinophils, neutrophils and lymphomononuclear cells were counted. The amount of smooth muscle shortening, the areas of airway wall, smooth muscle, mucous gland and cartilage were measured. Cell counts, airway dimensions and muscle shortening were compared in cases dying within 2 h of the fatal attack (short duration) and those dying more than 5 h after the onset of the fatal attack (long duration). In cases with fatal attacks of short duration, the numbers of neutrophils and the mucous gland area were increased and the numbers of eosinophils were reduced compared to cases with fatal attacks of long duration. Lymphocyte numbers, airway wall thickness, the areas of smooth muscle and cartilage and the amount of smooth muscle shortening were similar in the two groups. These findings suggest fatal attacks of asthma may be triggered by an inflammatory stimulus and suggest that increased production of mucous may contribute to sudden death in such cases.

Adolescent

Pattern of performance in workers with low back pain during a comprehensive motor performance evaluation.

STUDY DESIGN: Tests of limb and back motor performance were administered to males with low back pain at the completion of a back-school program. OBJECTIVES: The objective of the study was to determine the relationship between such motor performance and the propensity for abnormal illness behavior as indicated by the Waddell score. SUMMARY OF BACKGROUND DATA: Previous studies in similar subjects had revealed a nonbiologic pattern of lumbar strength and movement in back-school patients, and correlations between lumbar variables, Waddell score, and 'global' psychologic measures. This suggested that psychologic factors might affect motor performance in body segments unrelated to the low back in such patients. RESULTS: Mean performance of the group with a high Waddell score (indicating a propensity for abnormal illness behavior) was lower on all tests, including those that did not involve the low back, in comparison to the group with a low Waddell score (P < .01, sign test). CONCLUSION: For all members of this population of patients, motor performance on dynamometry of any body segment does not necessarily reflect the maximum physical capacity.

Adult

Relationship of performance on the ERGOS work simulator to illness behavior in a workers' compensation population with low back versus limb injury.

A prospective blinded cohort study was performed to test for a difference in the pattern of physical activity factors measured with the ERGOS work simulator in subjects with low back injuries versus those with limb injuries. Also tested was the relationship between physical activity factors measured with the ERGOS and several psychological tests and measures of nonorganic pain behavior in subjects with low back pain. Subjects were 70 men, 22 to 64 years old, who attended a 2-week physical capacity assessment after undergoing rehabilitation for a work-related injury. In subjects with a complaint of low back pain, nonorganic pain behavior was measured with the Waddell score. In addition, two brief psychological tests, the Coopersmith Self-Esteem Inventory and analog self-rating of wellness, were administered. It was found that subjects with low back complaints underperformed globally in comparison with subjects with limb complaints. This underperformance was statistically significant (P < .05) for 7 of 13 strength variables and 2 of 7 dexterity variables. In the subjects with low back complaints, those who exhibited excessive illness behavior (Waddell score, 3 to 5) performed significantly worse on all 13 strength variables and on 3 of 7 dexterity variables. In the subjects with low back complaints, those with low self-assessment ratings were found to have a high Waddell score (P < .01) and to perform significantly worse (P < .05) on 12 of 13 strength variables and 6 of 7 dexterity variables. There were no significant relationships (P > .05) between Coopersmith Self-Esteem score and Waddell score or performance on ERGOS testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Expression of the La Crosse M segment proteins in a recombinant vaccinia expression system mediates pH-dependent cellular fusion.

To study the expression of La Crosse virus (LAC) glycoproteins, G1 and G2, we constructed a cDNA copy of the open reading frame (ORF) of the middle RNA segment and expressed it in a recombinant vaccinia virus (VV.ORF). Cells infected with VV.ORF expressed G1 and G2 at the cell surface and formed syncytia with a pH profile similar to that of LAC. These experiments provide a system of studying the biological functions of the LAC glycoproteins, including processing, targeting, fusion, receptor binding, and antigenicity.

Animals

Concurrent validity of the ERGOS work simulator versus conventional functional capacity evaluation techniques in a workers' compensation population.

A prospective blinded cohort study was performed in an interdisciplinary vocational evaluation program to investigate the concurrent validity of the ERGOS work simulator in comparison to current methods of evaluation. Seventy men and eight women, aged 22 to 64 years, who attended for a 2-week physical capacity assessment participated in the study. Physical activity factors as defined by the Canadian Classification and Dictionary of Occupations and the American Dictionary of Occupational Titles were assessed for all subjects under three evaluation conditions: the ERGOS work simulator, an exercise-oriented physical evaluation by a rehabilitation therapist, and performance of project-format industrial tasks. In addition, 17 men and 7 women were assessed with VALPAR standardized work sample tests. The statistical significance of the relationships between results obtained by the various evaluation methods was examined. There was a strong correlation between the ERGOS dynamometry and the clinical assessment of strength for all standard movements tested (P < .001). The Methods Time Measurement rating by the ERGOS for dexterity variables, according to industrial engineering standards, tended to rate subjects as more restricted than did the clinical evaluators. There was a significant relationship (P < .001) between the "overall physical activity rating" from ERGOS dynamometry, clinical evaluation, and performance in an industrial workshop setting. There was also a significant relationship (P < .001) between the "overall physical activity rating" for endurance of a full workday produced by the 4-hour ERGOS evaluation and by the 2-week functional capacity evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Serial lumbar dynamometry in low back pain.

To determine the significance of changes in motor performance as measured by lumbar dynamometry, serial lumbar dynamometry was performed on a group of 45 male Workers' Compensation patients with chronic "mechanical" low back pain and in a group of 20 healthy male volunteers. The patients were men aged 20-60 years, whose current episode of low back pain had lasted for at least 3 months (mean 19.5 weeks, range 12-47 weeks). Testing was performed at entry into a "back school" program of therapy and again 2 weeks and 4 weeks later. The control group showed a slight improvement in almost all variables of strength and range of motion between the first and second tests but no significant change between the second and third tests. This was consistent with a learning effect. The patient group was analyzed as a whole and also in two groups based on their response to the Waddell maneuvers at entry: Waddell score 0-2 (no excessive illness behavior) and 3-5 (excessive illness behavior). As a whole, the patients showed significant progressive improvement in most variables on successive tests. The group with the low Waddell score had significantly greater strength and range of motion than the group with the high Waddell score but the trend of improvement with time was similar in the two groups. The authors conclude that in this sample of patients with low back pain, serial lumbar dynamometry reveals a progressive improvement in performance, which is greater than the improvement expected from the natural history of physical recovery and greater than the improvement expected from an increase in strength and range of motion attributable to the therapeutic exercises performed and is much larger than any learning effect related to the test procedure.

Adult

Definition of the upstream efficiency element of the simian virus 40 late polyadenylation signal by using in vitro analyses.

The polyadenylation signal for the late mRNAs of simian virus 40 is known to have sequence elements located both upstream and downstream of the AAUAAA which affect efficiency of utilization of the signal. The upstream efficiency element has been previously characterized by using deletion mutations and transfection analyses. Those studies suggested that the upstream element lies between 13 and 48 nucleotides upstream of the AAUAAA. We have utilized in vitro cleavage and polyadenylation reactions to further define the upstream element. 32P-labeled substrate RNAs were prepared by in vitro transcription from wild-type templates as well as from mutant templates having deletions and linker substitutions in the upstream region. Analysis of these substrates defined the upstream region as sequences between 13 and 51 nucleotides upstream of the AAUAAA, in good agreement with the in vivo results. Within this region, three core elements with the consensus sequence AUUUGURA were identified and were specifically mutated by linker substitution. These core elements were found to contain the active components of the upstream efficiency element. Using substrates with both single and double linker substitution mutations of core elements, we observed that the core elements function in a distance-dependent manner. In mutants containing only one core element, the effect on efficiency increases as the distance between the element and the AAUAAA decreases. In addition, when core elements are present in multiple copies, the effect is additive. The core element consensus sequence, which bears homology to the Sm protein complex-binding site in human U1 RNA, is also found within the upstream elements of the ground squirrel hepatitis B and cauliflower mosaic virus polyadenylation signals (R. Russnak, Nucleic Acids Res. 19:6449-6456, 1991; H. Sanfacon, P. Brodmann, and T. Hohn, Genes Dev. 5:141-149, 1991), suggesting functional conservation of this element between mammals and plants.

Base Sequence

Normative database for trunk range of motion, strength, velocity, and endurance with the Isostation B-200 Lumbar Dynamometer.

A review of related literature and trends was used to develop a protocol for testing range of motion, isometric strength, velocity, endurance, and consistency of effort in the low-back pain (LBP) population by the use of the triaxial, Isostation B-200 Lumbar Dynamometer. Eighty-five men and 83 women with no history of LBP for the past 6 months volunteered for the study. Relationships between demographic and test measures were calculated by the use of the Pearson r correlation analysis and ANOVA. Body weight, age, and gender all showed strong (P less than .001), positive relationships to various test measures. The normative database is reported in terms of descriptive statistics allowing comparison of future test results within the normal distribution and corrected for significant demographic features.

Adult

Relationship between performance on lumbar dynamometry and Waddell score in a population with low-back pain.

A prospective, blinded cohort study was performed to investigate the relationship between biomechanical variables measured during lumbar dynamometry and several psychological tests and measures of nonorganic pain behavior. Eighty-five men, aged 18-60 years, who had had low-back pain for longer than 5 weeks participated in the study. Nonorganic pain behavior was measured with the Waddell score, and lumbar function was measured with the Isostation B-200 Lumbar Dynamometer. Two brief psychological tests, the Coopersmith Self-Esteem inventory and an analog self-rating of wellness, were also administered. Relationships between biomechanical variables and psychological tests were calculated with the t-test, the Pearson r correlation, analysis of variance, and multiple step-wise logistic regression. Patients who exhibited excessive illness behavior (Waddell Scores 3-5) performed significantly worse (P less than .01) on almost all biomechanical variables. The Coopersmith Self-Esteem Score and "feelings" score had a slightly weaker but still significant correlation with motor performance. The results suggest that poor performance on biomechanical testing in this population may be a form of abnormal illness behavior and thus may not accurately reflect organic alterations of neuromusculoskeletal function.

Adult

Selective cytoplasmic and membrane changes induced by cisplatinum.

Cisplatinum (cis-dichlorodiammineplatinum II (NSC-119875], proven to be of therapeutic value in a variety of solid tumors, is thought to have DNA as its major target. Prior in vitro studies have suggested that it also induced cell membrane and cytoplasmic changes. To better understand glial tumor cell sensitivity to cisplatinum and to design more effective adjuvant therapy, three cisplatinum sensitive human glioma-derived cell lines, SNB-1, SNB-3, SNB-4, were examined by transmission electron microscopy for cisplatinum induced changes. Tumor cells were exposed to 25, 50, and 100 micrograms/ml cisplatinum in medium for varying time periods (4-72 hours). Four changes were consistent: cell rounding and reduced nuclear-cytoplasmic ratio, nuclear chromatin clumping, vesiculation and swelling of the golgi apparatus, and dilatation of the smooth endoplasmic reticulum. These morphologic changes are distinct for cisplatinum and unlike those induced by BCNU (plasma membrane blebbing) and AZQ (mitochondrial swelling and destruction) previously seen in our laboratory. The cellular events described here suggest that cytoplasmic, as well as nuclear, changes (occurring within the same time intervals) may both be relevant to the antitumor effects of cisplatinum.

Cell Line

Ageing and isokinetic plantar flexion.

Isokinetic torques (Cybex II) of the plantar flexors in 25 healthy men were compared at 5 angular velocities (30, 60, 90, 120 and 180 degrees X s-1). The purposes were to compare plantar flexion torques in young and old subjects, and to determine whether the expected decrease was significantly associated with age, physical activity, or aerobic fitness. Four groups were studied: young (21.7 +/- 2.0 years) and older (63.3 +/- 2.8 years), active and sedentary. Measurements of height, weight, % body fat, VO2max, and daily leisure energy expenditure (questionnaire) were determined for each subject. Statistical measures of analysis of variance were used to determine significant differences among groups; product moment correlation and stepwise regression analysis were used to describe the degree of association between the dependent variable of plantar flexion torque and the independent variables at each velocity. A decline in torque was observed as the isokinetic velocity of angular motion increased. Age alone was a significant determinant of plantar flexion torque, whereas at the slowest speed, when VO2max was used as an explanatory variable, age was not a significant determinant of torque. At 30 degrees X s-1 47% of the variance in torque was explained by VO2max while at 180 degrees X s-1 49% of the variance was explained by age.

Adult

Retinoblastoma with anterior chamber extension.

Anterior chamber retinoblastoma is a rare clinical entity. The authors have reviewed the records of 1500 patients with retinoblastoma to determine the incidence and prognostic ramifications. Of 30 patients with anterior chamber involvement, 15 were noted on initial examination and 15 during observation after therapy. Despite aggressive multimodality treatment, total response was never achieved and all eyes were eventually lost. Results of pathologic examination showed ciliary body invasion, which was held accountable for the poor response to therapy. Anterior chamber retinoblastoma is a poor prognostic sign which cannot be controlled effectively with current techniques and should be considered an indication for enucleation without delay.

Child

The kinetochore is part of the metaphase chromosome scaffold.

We used antisera from patients with the CREST syndrome of scleroderma (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) to show that an antigenic component of the kinetochore present in metaphase chromosomes is also present in nonhistone chromosome scaffolds isolated following extensive digestion of the DNA and extraction of the bulk of chromosomal protein. All sera from 12 scleroderma CREST patients previously shown by immunofluorescence microscopy to have circulating antikinetochore antibodies recognise a protein of Mr 77,000 (CREST-77) in an immunoblotting assay. 9 of the 12 sera also recognise an antigen of Mr 110,000 (CREST-110). These proteins are present in isolated chromosomes and nonhistone scaffolds derived from them by two different procedures. Sera of five scleroderma CREST patients who are antikinetochore negative (by immunofluorescence) bind to neither protein in immunoblots. These data suggest that CREST-77 (and possibly CREST-110) is a component of the human kinetochore, and that the kinetochore is an integral part of the mitotic chromosome scaffolding.

Autoantibodies