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Biomedical subjects

M Collins

Publications and source records attributed to M Collins.

At least 163 records · Page 9Linked to original sources
PubMed1994

Valproate-mediated disturbances of hemostasis: relationship to dose and plasma concentration.

Valproic acid (VPA) may cause impaired platelet function, thrombocytopenia and, occasionally, severe bleeding. Controversy exists both as to the mechanism of this alteration in hemostasis and as to whether these adverse effects are either dose-related or idiosyncratic. Previous investigations have focused primarily on pediatric patients who commonly were receiving multiple anticonvulsant medications. We evaluated a cohort of 27 adult patients with epilepsy who were receiving VPA monotherapy and compared them with age-matched controls to determine whether a correlation exists between platelet count, function, bleeding time, levels of von Willebrand's factor antigen, and VPA dose or plasma concentration. VPA patients had significantly lower platelet counts and longer bleeding times than did controls (p < 0.05). Platelet count was inversely correlated to VPA dose and both free and total VPA concentration (p < 0.01). There was no significant difference in levels of von Willebrand's factor antigen between patients and controls. We assessed platelet aggregation by measurement of whole-blood platelet aggregation and release with agonists including adenosine diphosphate, thrombin, collagen, arachidonic acid, and ristocetin. VPA patients had significant decreases in platelet aggregation values compared with controls. There were significant differences in collagen, arachidonic acid, and adenosine diphosphate release and aggregation between groups that correlated to both VPA dose (p < 0.01) and concentration (p < 0.05). Prolongation of bleeding time was significantly correlated to both VPA dose and concentration. Our data suggest a significant relationship between impaired platelet function and both VPA dose and plasma concentration.

Adult↗
PubMed1994

Contamination of disinfection solution bottles used by contact lens wearers.

We investigated the contamination of disinfection solution bottles after 2 weeks of patient use. Forty-four subjects participated in the study and each used three soft lens care systems (cross-over study). The order in which the three care systems were dispensed was randomized to eliminate systematic bias. Sixteen subjects used only one of the systems (disinfection solutions) over three consecutive 2-week periods (reliability study). Contamination of the disinfection solution bottles occurred in 12 of the 180 bottles sampled (7%), and the level of contamination of these bottles ranged up to 10(5) colony forming units per milliliter. A wide range of microorganisms was identified in these positive samples, many of which were potential ocular pathogens. None of the subjects in the study (n = 60) showed contamination in more than one of the three solution bottles sampled, suggesting that the phenomenon was not strongly patient specific. The rate of contamination of disinfection solution bottles was not influenced by contact lens wearing experience (i.e., familiarity with care procedures), by the time of year (season) at which the samples were collected, or by the subjects' compliance with hand washing. However, among the 44 subjects in the cross-over study, the rate of contamination of disinfection solution bottles was influenced by the type of disinfection solution.

Bacteria↗
PubMed1993

Glucocorticoid hormones upregulate interleukin 2 receptor alpha gene expression.

We present evidence that glucocorticoid hormones increase expression of IL-2Rec alpha chain on T cells by regulating IL-2Rec alpha gene transcription. We have previously reported that glucocorticoids can upregulate IL-2Rec alpha mRNA and protein expression in some T cell hybrids. In the present study we show that the glucocorticoid analogue dexamethasone increases mRNA levels of the endogenous IL-2Rec alpha gene and the expression of plasmids containing 5'-flanking sequences of the IL-2Rec alpha gene linked to CAT reporter genes transiently transfected into different cell lines. We show that the dexamethasone effect depends on cis-acting regulatory elements in a segment (-1835/-802) of the mouse gene that also contains cytokine response elements and a inducible DNase I-hypersensitive site. Dexamethasone responses of IL-2Rec alpha-CAT reporter gene constructs were observed in a CTL line, in an IL-3-dependent bone marrow-derived cell line, and in COS7 monkey kidney cells. In the latter the response depended on cotransfection of a glucocorticoid receptor expression vector. The biological relevance of the glucocorticoid-mediated upregulation of the IL-2Rec alpha gene is discussed.

Animals↗
PubMed1993

Granulocyte activation induced by intense interval running.

Activation of granulocytes has been associated with normal immune function, inflammation, and exercise-induced muscle damage. The effect of intense interval running on granulocyte activation was examined by use of flow cytometry, monoclonal antibodies, and spectrophotometric techniques. Eight trained males [maximal oxygen uptake VO2max, mean (SD) = 64.4 (3.6) ml/kg/min; age 30.1 (4.8) years] undertook an intense interval exercise (treadmill running) protocol to exhaustion. Subjects completed an average of 16.5 one-minute runs. Granulocyte expression of CR3 (CD11b), receptor for complement component C3bi (6 and 24 h post-test), and Fc gamma RIII (CD16) (24 h post-test) and the plasma concentration of elastase-inhibitor complex (1 h post-test) increased significantly (all P < .05). Subjects (8 of 8) exhibited a post-test decrease at either 1 or 6 h (P < .01) and a 24-h post-test significant increase (7 of 8; P < .05) in granulocyte 90 degrees light scattering (LS). Plasma lactoferrin (Lf) concentration, although increased by 17% at 6 h post-test, was not significantly different from resting values at any sampling point. Changes in plasma Lf and median channel 90 degrees LS were significantly correlated (r = -.43, P = .04), raising the possibility of monitoring exercise-induced granulocyte activation (degranulation) by flow cytometry. Intense interval exercise appears to induce granulocyte activation, as manifested by release of granule proteins and changes in 90 degrees LS and expression of both Fc and complement receptors.

Adult↗
PubMed1993

The role of bone scintigraphy in detecting child abuse.

This review of diagnostic imaging in cases of suspected child abuse characterizes the significant differences between bone scintigraphy and x-ray evaluation, describes the advantages and disadvantages of each modality, postulates on the specific mechanisms of injury that produce the characteristic scintigraphic findings, and emphasizes the influences that scintigraphic studies have on the medical, social, and legal aspects of child abuse. The major advantages of bone scintigraphy are its increased sensitivity (25% to 50%) in detecting evidence of soft tissue as well as bone trauma in child abuse. Furthermore, it is postulated that the specific mechanisms of inflicting the trauma relate to the patient's size and are characterized by bone scintigraphy. During fits of anger or frustration, the perpetrator of child abuse grasps the small infant or child by the thorax during the shaking activity. This produces characteristic rib injuries. The older and heavier child is more likely to be grabbed by the extremities, which produces periosteal injuries manifested as characteristic abnormal localizations in the diaphyses of the extremities. The roentgenograms of these injuries are frequently normal. The importance of bone scintigraphy is its complementary nature in defining and characterizing the extent and severity of trauma from child abuse. Such findings have direct bearing on the medical, social, and legal outcomes for the abused child. The quality of scintigraphic imaging is important, requiring the use of magnification techniques in the infant. The interpretation of the scintigraphic images depends on an understanding of the mechanisms by which the radionuclide localizes in bone. The same traumatic incident can lead to decreased, normal, or increased localization at the trauma site. Radionuclide scintigraphy is a complementary rather than competitive imaging modality to X-ray evaluation in the diagnosis and management of physical child abuse.

Bone and Bones↗
PubMed1993

Prematriculation immunization requirements of American colleges and universities.

The authors surveyed a stratified sample of 880 colleges and universities in the United States to assess the status and characteristics of their prematriculation immunization requirements (PIRs). On the basis of a 90% return (796 responses), they estimated that 55% of US colleges and universities had implemented a PIR at the time of the survey. Among schools with PIRs, measles vaccine was almost universally required, with 74% requiring two doses, mumps vaccine was required by 70%, and rubella vaccine by 92%. Hepatitis B vaccine was rarely required and was usually recommended only for students in health-profession programs. The strongest determinant of having a PIR was the presence of a state law or regents' policy. PIRs implemented under the aegis of a state law were, on average, less comprehensive but better enforced. Other factors associated with the implementation of a PIR included membership in the American College Health Association (ACHA), the presence of a student health clinic, and availability of record-keeping personnel.

Adolescent↗
PubMed1993

Distance visual acuity and monovision.

We have investigated aspects of visual acuity with monovision correction. Binocular distance visual acuity with monovision was approximately equal to monocular visual acuity for addition powers (monocular defocus) of +1.00 to +2.50 D, using both high and low contrast logMAR visual acuity charts. Neither the eye chosen to be defocused (dominant or nondominant) or pupil size (3.5, 5 and 7 mm) affected the binocular visual acuity loss with monovision for high contrast charts. We also investigated the effect of induced residual astigmatism (+0.50, +1.00, and -1.00 D) on binocular distance visual acuity in monovision correction. Residual astigmatism caused a significantly greater reduction of binocular visual acuity in the monovision condition than it did in normal binocular conditions. This effect appears to be related to a process of meridional interocular suppression. It may therefore be of clinical importance to correct low amounts of residual astigmatism in monovision corrections to provide optimum binocular visual acuity.

Adult↗
PubMed1993

Calibration of the Canon Autoref R-1 for continuous measurement of accommodation.

The Canon Autoref R-1 is an infrared optometer which allows free-space viewing. Pugh and Winn described hardware modifications necessary to convert the Autoref R-1 from an instrument capable of taking single static measurements of the eye's accommodative (refractive) status to an instrument capable of continuous measurement of the accommodative status of the eye. We describe two methods of calibrating the Autoref R-1 for continuous measurement of accommodation for any individual eye. The assumptions and sources of error underlying these calibration techniques are discussed. We also describe further hardware modifications to simplify signal acquisition from the Autoref R-1.

Accommodation, Ocular↗
PubMed1993

The distribution of free and non-ionic vesicular sodium stibogluconate in the dog.

The pharmacokinetics and tissue distribution of antimony after the administration of sodium stibogluconate in a free form or entrapped in vesicles prepared from non-ionic surfactant were studied in the dog. Animals were given either one or two intravenous bolus injection(s) equivalent to 45 mg Sb kg-1 as free drug or 0.625 or 0.685 mg Sb kg-1 as vesicular drug. Blood samples were taken at various times after dosing and antimony levels in various tissues were determined at 3 h, 48 h and 6 days after dosing. After free stibogluconate antimony clearance from the blood occurred in a rapid elimination phase with a blood half-life of 0.58 +/- 0.08 h. This rapid elimination phase did not occur after vesicular drug. Both drug preparations gave similar antimony levels in the spleen, liver and femur and humerus bone marrow at all time points assessed even though the vesicular dose was one-seventieth of the free drug dose. After the free drug there was marked urinary excretion of antimony and, as a result, increased kidney loading at the expense of other tissue. Vesicle-mediated drug delivery suppressed renal excretion and a much greater proportion of the antimony dose was recovered from tissue than was obtained after free drug. A hypothesis is presented to account for the differences in tissue antimony concentrations produced by the two formulations.

Animals↗
PubMed1993

The response of leukocyte subsets and plasma hormones to interval exercise.

Aerobic exercise has an established role in modulation of peripheral leukocyte concentrations. However, the effects of intense interval exercise, as employed by athletes in a range of sports, has been given little attention. Eight trained male athletes of mean age (SD) = 31.5 (4.5) yr; VO2max = 64.3 (3.8) ml.kg-1.min-1 undertook an intense interval exercise protocol (treadmill running) to exhaustion. Subjects completed an average of 15.6 1-min efforts. The protocol produced a biphasic leukocytosis: an initial (immediately posttest) leukocytosis resulting from mobilization of lymphocytes (CD3+, CD4+, CD8+, CD16+/56+, CD3+HLA/DR+) (all P < 0.01), with the later (6 h) leukocytosis resulting from mobilization of granulocytes and monocytes (both P < 0.01). This protocol modified significantly the peripheral blood concentration of the hormones cortisol (both total and free), norepinephrine, DHPG, and dopamine (all P < 0.01). Modulation of peripheral leukocyte subsets induced by interval exercise correlated with both the number of exercise efforts performed and the concomitant changes in peripheral hormone concentrations. Sustained alterations in plasma catecholamine levels in the posttest period may have important metabolic and immunological implications for athletes undertaking regular interval training.

Adult↗
PubMed1993

A palindromic element in the human immunodeficiency virus long terminal repeat binds retinoic acid receptors and can confer retinoic acid responsiveness on a heterologous promoter.

A palindromic element (site B) located between bases -328 and -347 (relative to the start site of transcription) of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) was shown in a gel mobility shift assay to bind the human retinoic acid receptors (RARs). Greatly enhanced binding to this site was observed in the presence of both RAR and the retinoid X receptor. Retinoic acid responsiveness in F9 cells could be conferred on a thymidine kinase promoter by the presence of single or multiple copies of site B and responsiveness was abolished when this sequence was mutated to a form that could not bind RARs. However, the presence of this sequence did not render the HIV-1 LTR responsive to retinoic acid in F9 cells.

Animals↗
PubMed1993

Influence of atherosclerosis on the vascular reactivity of isolated human epicardial coronary arteries to leukotriene C4.

Leukotrienes, lipid mediators derived from arachidonic acid by the 5-lipoxygenase pathway, have been implicated in a variety of myocardial ischemic events including myocardial infarction and coronary spasm. We have examined the comparative effects of leukotriene C4 in isolated human non-atherosclerotic and atherosclerotic coronary arteries to gain an insight into the role of leukotrienes in coronary heart disease. Human coronary arteries, obtained from recipient hearts at the time of cardiac transplantation, were cut into rings and examined in an isolated organ bath. In atherosclerotic arteries leukotriene C4 (1nM-100nM) produced a maximal contractile response of 54.9 +/- 7.98% KCI (n = 7) and the mean EC50 value was 11.1nM (95% confidence interval: 9.4-13.0). The leukotriene receptor antagonist ICI-198,615 (3 x 10(-8)M) produced an approximate 50-fold rightward shift of the leukotriene C4 dose-response curve (n = 5). In contrast, non-atherosclerotic arteries were either non-responsive (n = 5) or only weakly responsive (n = 2) to leukotriene C4 (1nM-100nM), producing an average maximum response of 3.65 +/- 3.05% KCI (n = 7; p < 0.01 atherosclerotic vs non-atherosclerotic). In the presence of indomethacin and in vessels denuded of endothelium, non-atherosclerotic arteries remained unresponsive to leukotriene C4 (n = 3). In addition, leukotriene C4 did not relax preconstricted vessels (n = 7). In vitro autoradiography showed specific [3H]-leukotriene C4 binding to smooth muscle in both non-atherosclerotic and atherosclerotic arteries, with no evidence of endothelium-dependent binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

The abolition of collagen gene expression in SV40-transformed fibroblasts is associated with trans-acting factor switching.

The goal of this study was to determine whether alpha 2(1) procollagen gene expression is modulated by positive or negative trans-acting DNA-binding proteins. Previous studies have shown that a clone of SV40-transformed WI-38 fibroblasts (SVWI-38) does not produce any alpha 2(1) procollagen mRNA (Parker et al (1989), J. Biol Chem. 264, 7147-7152). In order to elucidate the mechanism(s) responsible for such inactivation, we have examined the activity of a transfected wild type COL1A2 promoter in SVWI-38 cells. A set of 5' promoter deletions was linked to the chloramphenicol acetyltransferase (CAT) gene and transfected into SVWI-38 and other cell lines expression type I collagen. The resulting CAT assays confirmed the importance of several upstream regions for promoter activity and documented the decreased transcriptional activity from an exogenous COL1A2 promoter in the SVWI-38 cell line. Competition experiments with an excess of COL1A2 promoter DNA fragment and a constant amount of COL1A2/CAT construct displayed a linear relationship between excess COL1A2 fragment and CAT activity in SVWI-38 cells, suggesting the involvement of a titratable negative effector. Electrophoretic mobility shift assays revealed the presence of a specific DNA-protein complex which was present in SVWI-38 cells and almost absent in control fibroblasts. Methylation interference analysis mapped the region of binding of this factor between nucleotides -80 and -72, relative to the transcription start site. Thus the data presented provide strong evidence for the existence of a negative trans-acting factor that may play a role in the repression of COL1A2 expression in SVWI-38 fibroblasts.

Base Sequence↗
PubMed1992

Characterization of a novel T lymphocyte protein which binds to a site related to steroid/thyroid hormone receptor response elements in the negative regulatory sequence of the human immunodeficiency virus long terminal repeat.

We have previously identified a T lymphocyte protein which binds to a site within the LTR of the human immunodeficiency virus type 1 (HIV-1) and exerts an inhibitory effect on virus gene expression. The palindromic site (site B) recognized by this protein is related to the palindromic binding sites of members of the steroid/thyroid hormone receptor family. Here we characterize the T cell protein binding to this site as a 100 kD protein which is most abundant in T cells and which binds to site B as a 200 kD complex. This protein is distinct from other members of the steroid/thyroid hormone receptor family including the COUP protein which has a closely related DNA binding specificity.

Base Sequence↗