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Biomedical subjects

J R Turner

Publications and source records attributed to J R Turner.

At least 55 records · Page 3Linked to original sources
PubMed1997

Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation.

Tight junctions serve as the rate-limiting barrier to passive movement of hydrophilic solutes across intestinal epithelia. After activation of Na+-glucose cotransport, the permeability of intestinal tight junctions is increased. Because previous analyses of this physiological tight junction regulation have been restricted to intact mucosae, dissection of the mechanisms underlying this process has been limited. To characterize this process, we have developed a reductionist model consisting of Caco-2 intestinal epithelial cells transfected with the intestinal Na+-glucose cotransporter, SGLT1. Monolayers of SGLT1 transfectants demonstrate physiological Na+-glucose cotransport. Activation of SGLT1 results in a 22 +/- 5% fall in transepithelial resistance (TER) (P < 0.001). Similarly, inactivation of SGLT1 by addition of phloridzin increases TER by 24 +/- 2% (P < 0.001). The increased tight junction permeability is size selective, with increased flux of small nutrient-sized molecules, e.g., mannitol, but not of larger molecules, e.g., inulin. SGLT1-dependent increases in tight junction permeability are inhibited by myosin light-chain kinase inhibitors (20 microM ML-7 or 40 microM ML-9), suggesting that myosin regulatory light-chain (MLC) phosphorylation is involved in tight junction regulation. Analysis of MLC phosphorylation showed a 2.08-fold increase after activation of SGLT1 (P < 0.01), which was inhibited by ML-9 (P < 0.01). Thus monolayers incubated with glucose and myosin light-chain kinase inhibitors are comparable to monolayers incubated with phloridzin. ML-9 also inhibits SGLT1-mediated tight junction regulation in small intestinal mucosa (P < 0.01). These data demonstrate that epithelial cells are the mediators of physiological tight junction regulation subsequent to SGLT1 activation. The intimate relationship between tight junction regulation and MLC phosphorylation suggests that a critical step in regulation of epithelial tight junction permeability may be myosin ATPase-mediated contraction of the perijunctional actomyosin ring and subsequent physical tension on the tight junction.

Animals↗
PubMed1997

Predictors of Pneumocystis carinii pneumonia in HIV-infected persons. Pulmonary Complications of HIV Infection Study Group.

The Pulmonary Complications of HIV Infection Study is a prospective, multicenter, observational study evaluating pulmonary disease among HIV-infected persons. For approximately 52 mo, 1,182 HIV-infected subjects were followed. All participants were evaluated for pulmonary disease on a predetermined schedule. There were 145 episodes of Pneumocystis carinii pneumonia (PCP). Low CD4 count correlated with risk of PCP (p < 0.0001); 79% had CD4 counts less than 100/microl and 95% had CD4 counts less than 200/microl. Subtle changes in diffusing capacity for carbon monoxide (DLCO) were associated with PCP. Univariate analysis identified recurrent undiagnosed fevers, night sweats, oropharyngeal thrush, and unintentional weight loss to be associated with risk among persons with CD4 counts above 200/microl. Subjects in whom CD4 counts declined to below 200/microl and who were not receiving preventive therapy were nine times more likely to develop PCP within 6 mo compared with subjects who received such therapy. A strong trend toward differences between the sexes was detected. Black subjects had less than one third the risk of developing PCP as did white subjects (p < 0.0001). There was no significant difference in risk by HIV transmission category, study site, frequency of follow-up, age, education, smoking history, or use of antiretroviral therapy. Multivariable analysis revealed low CD4 lymphocyte count (p < 0.0001), use of prophylaxis (p < 0.0001), racial differences (p < 0.0001), and declining DLCO (p = 0.015) to influence risk. Constitutional signs and symptoms indicate increased risk for PCP among HIV-infected persons with CD4 counts above 200/microl.

AIDS-Related Opportunistic Infections↗
PubMed1997

Prediction of resting cardiovascular functioning in youth with family histories of essential hypertension: a 5-year follow-up.

Two hundred forty-six children (96 Whites, of whom 51 were males; 150 African- Americans, of whom 69 were males) with a familial history of essential hypertension (EH) were re-evaluated 5 years after an initial evaluation. During the initial visit anthropometric, demographic, and resting cardiovascular (CV) parameters (designated initial baseline levels) were assessed. These CV parameters (systolic and diastolic blood pressure [BP], heart rate, cardiac output index [CI], and total peripheral resistance index [TPRI] were also measured during postural challenge, a video game challenge, and a cold pressor task. At follow-up, resting CV parameters were again evaluated, and designated as follow-up resting levels. Moderate temporal stability (r range = .43-.56) was observed for all resting CV parameters. Mean stress responses for each CV parameter for all 3 stressors during the initial visit were positively related to the respective CV follow-up resting level. BP stress responses to postural change and video game challenge to be significant independent predictors of future resting BP after controlling for standard EH risk factors. Follow-up resting CI was not predicted by any stress responses, whereas follow-up resting TPRI was predicted by TPRI responses to the video game after controlling for standard Eh risk factors. These results contrast with those from an earlier 1-year follow-up, where stress responses for neither CI nor TPRI predicted follow-up resting levels. It appears that, as children get older, TPRI stress responses play a stronger role in vasoconstrictive function.

Journal Article↗
PubMed1997

Off-axis output factors for 6MV and 18MV photons.

A series of in-air measurements showed that collimator scatter (Sc) did not change significantly for 6MV photons when the centre of the field was moved away from the central axis. This result enabled a model to be developed for the off-axis Effective Output Factor (EOF) which was then verified for 6MV and 18MV photons on a Varian 2100c accelerator and for 6MV photons on a Varian 600c accelerator. Thus off-axis output factors may be predicted, for a range of rectangular asymmetric fields, using only the Primary Off-Centre Ratio (POCR) in air and the on-axis output factor. Depth doses were also investigated off-axis and found to have no clinically significant differences compared with on-axis depth doses, for depths less than 7.5 cm for 6MV and 12.5 cm for 18MV photons. The model is simple to implement and avoids the need for a measurement for each patient, thus saving accelerator time.

Biophysical Phenomena↗
PubMed1996

Production of a novel polyketide through the construction of a hybrid polyketide synthase.

The lactone rings of the polyketides platenolide and tylactone are synthesized by condensation of acetate-, proprionate-, and butyrate-derived precursors. A hybrid tylactone/platenolide synthase was constructed to determine if the choice of substrate is programmed by the polyketide synthase and to ascertain if a substrate different than that normally used in the first step of platenolide synthesis could be incorporated into the final polyketide. In this work, we report the successful incorporation of a propionate in place of the acetate normally used in the first step of platenolide synthesis. This result demonstrates that polyketide synthases choose a particular substrate at defined steps and provides strong evidence that substrate choice is programmed by the acyl transferase domain of a large, multifunctional polyketide synthase.

Acyl Coenzyme A↗
PubMed1996

Persistent clonal expansions of peripheral blood CD4+ lymphocytes in chronic inflammatory bowel disease.

It is increasingly recognized that chronic Ag exposure may lead to clonal expansions of T cells, including those within the peripheral blood. Inflammatory bowel disease is a chronic, multisystemic disease of unknown origin that predominantly affects the intestine. We sought to determine whether clonal expansions of T cells are present in the peripheral blood of patients with inflammatory bowel disease by an examination of TCR usage. Positively selected CD4+ and CD8+ peripheral blood T cells were isolated from subjects with active ulcerative colitis, Crohn's disease, and diverticulitis and from normal controls. Analysis of complementarity determining region 3 lengths of 24 TCR-beta chain V region families from CD4+ and CD8+ peripheral blood T cells showed a skewed distribution in the three inflammatory groups, consistent with expansion of T cell clones, in comparison to the normally distributed pattern observed among the control donors. Random sequencing of the PCR amplification products of CD4+ peripheral blood T cells from the subjects with ulcerative colitis, Crohn's disease, and diverticulitis revealed reiterative TCR-beta chain sequences that were not found in the normal donors. In subjects with Crohn's disease, the reiterative TCR-beta chain sequences from the CD4+ peripheral blood T cells were persistent over at least a 1-yr period. The persistently expanded TCR-beta chain sequences of CD4+ peripheral blood T cells were identifiable in genomic DNA isolated from archival tissue of intestine from subjects with Crohn's disease and ulcerative colitis by Southern blotting and direct DNA sequencing. An identical twin pair, concordant for Crohn's disease, shared the same reiterative TCR-beta chain sequences in their CD4+ peripheral blood T cells. These studies show that chronic intestinal inflammation is associated with expansions of CD4+ peripheral blood T cells. Furthermore, in inflammatory bowel disease these T cell clonal expansions are persistent and shared among HLA-identical individuals, implicating a response to specific, persistent, and stimulating Ags in these diseases.

Amino Acid Sequence↗
PubMed1996

Carboxy-terminal vesicular stomatitis virus G protein-tagged intestinal Na+-dependent glucose cotransporter (SGLT1): maintenance of surface expression and global transport function with selective perturbation of transport kinetics and polarized expression.

The Na+-dependent glucose transporter (SGLT1) mediates absorption of luminal glucose by the intestine. However, available intestinal cell lines that recapitulate a monolayer phenotype only express SGLT1 at low levels. Thus, to facilitate studies of the biology of SGLT1 function in epithelial monolayers, we engineered an epitope-tagged construct containing the YTDIEMNRLGK sequence (from the vesicular stomatitis virus G protein). The tag was placed at the carboxyl terminus since this is the least conserved portion of SGLT1. Transiently transfected COS-1 cells demonstrated surface expression of the immunoreactive protein and enhanced Na+-dependent glucose uptake that was phloridzin-sensitive (a specific competitive inhibitor of SGLT1). However, subsequent detailed analyses of epitope-tagged SGLT1 using stably transfected clones derived from the Caco-2 human intestinal epithelial cell line revealed substantial effects of the epitope on critical functions of SGLT1. When compared with native SGLT1 transfectants, the apparent Km for sugar transport was increased 23-fold (313 microM to 7.37 mM for native versus epitope-tagged SGLT1). In contrast, the apparent KNa for epitope-tagged SGLT1 was similar to that for native SGLT1. Permeabilization studies indicated that the C-terminal epitope tag was intracellular and thus could not directly disrupt extracellular ligand-binding sites. Immunolocalization and functional assays designed to detect polarized surface expression indicated that epitope tagging resulted in loss of apical targeting and enrichment of basolateral expression. Functional isolation of the small apical pool of epitope-tagged SGLT1 (by selective inhibition of basolateral epitope-tagged SGLT1) revealed that, despite the documented kinetic alterations in sugar transport, epitope-tagged SGLT1 could promote absorptive Na+ currents. These data show that 1) the C terminus of SGLT1 is intracellular; 2) disruption of protein structure by addition of a C-terminal tag leads to selective modifications of SGLT1 function; 3) the kinetics of sugar transport can be altered independently of influences on the Na+-binding site of SGLT1; and 4) the weak basolateral targeting sequence present within the epitope tag is dominant over endogenous SGLT1 apical targeting information and can direct polytopic membrane protein localization. The data also caution that subtle effects of foreign sequences must be considered when epitope tagging polytopic membrane proteins.

Amino Acid Sequence↗
PubMed1996

Proliferative characteristics of differentiated cells in familial adenomatous polyposis-associated duodenal adenomas.

The authors have previously shown that duodenal adenomas in familial adenomatous polyposis (FAP) patients typically reveal abundant cells with endocrine differentiation (ED), Paneth differentiation (PD), and goblet cell differentiation (GD). However, the biological significance and proliferative potential of these cells is unknown. To study the proliferative properties of cells with ED, PD, or GD in FAP-associated duodenal adenomas, the authors used a double-labeling immunohistochemical technique to detect simultaneously the presence of proliferating cell nuclear antigen (PCNA), and either chromogranin or lysozyme in individual neoplastic cells. Adenomatous cells with GD were identified morphologically and also evaluated for the degree of PCNA expression by immunohistochemistry. Duodenal adenomas and the adjacent nonadenomatous epithelium from 10 FAP patients were studied. Cells with ED, PD, and GD were present in all adenomas, and constituted 14.1%, 11.6%, and 17.7% of adenomatous cells, respectively. The overall proliferative index of nondifferentiated adenomatous cells was 33.3%, which was similar to the proliferative index obtained for adenomatous cells with GD (31.2%) and nonadenomatous crypt goblet cells (34.9%). In contrast, adenomatous cells with ED and PD showed a significant decrease in their proliferative potential (P < .001). Only 6.0% and 7.3% of cells with ED and PD, respectively, were proliferative. Nonadenomatous crypt endocrine and Paneth cells showed no proliferative potential (proliferative index 0%). These results suggest that, in the process of proliferation and differentiation, specific subpopulations of adenomatous cells attempt to recapitulate the biological characteristics of their normal counterparts in the small intestinal crypts. Adenomatous cells with ED and PD are hypoproliferative, a finding that is consistent with their differentiated phenotype and suggests that these cells may not participate as actively in the growth of these lesions.

Adenoma↗
PubMed1996

High-resolution dosimetry using radiochromic film and a document scanner.

A method of reading exposed radiochromic film is described which has significant advantages over conventional densitometry. The method employs a document scanner and associated software for imaging the film. The resulting images are easily analysed using standard software to yield high-resolution dose maps. A calibration was performed which relates scanner signal to dose, allowing for the determination of dose at any point on an exposed film. Results obtained using a broad-band densitometer are compared to those where the scanner has been used. The technique was used to measure the dose distribution around a COMS-type ophthalmic applicator.

Densitometry↗
PubMed1996

The ability of active versus passive coping tasks to predict future blood pressure levels in normotensive men and women.

Casual blood pressure (BP) after a 2-year follow-up interval was determined in 40 normotensive men and women (20 Blacks and 20 Whites), who had been initially tested for cardiovascular responses to a variety of active and passive coping tasks, including active speech, passive speech, reaction time, and forehead cold pressor tasks. Stepwise multiple regression analyses were used to identify the best model for predicting follow-up BP. Average systolic blood pressure (SBP) level during cold pressor stress was the single most powerful predictor of casual SBP over 2 years even after controlling for initial resting SBP. Other predictors of follow-up SBP were initial SBP, parental history of hypertension, and heart rate and SBP during passive speech (final model R(2) = .78). For follow-up diastolic blood pressure (DBP), the only significant predictors were initial DBP and male gender. These results contribute to a growing body of literature that suggests that cardiovascular measures observed during stressors have predictive validity above and beyond that of traditional predictor variables.

Journal Article↗
PubMed1996

Young children's cardiovascular stress responses predict resting cardiovascular functioning 2 1/2 years later.

BACKGROUND: Since the pathogenesis of coronary heart disease (CHD) has its origins in childhood, researchers have increasingly evaluated CHD risk factors in youth. In this study we examined the hypothesized behavioral risk factor of cardiovascular responsivity as a predictor of very young children's resting cardiovascular functioning 2 1/2 years later. SUBJECTS AND METHODS: During an initial visit to the laboratory, 97 children (30 blacks and 67 whites, 45 boys and 52 girls) aged 6-7 years completed three laboratory stressor tests (forehead cold pressor, postural change, and treadmill exercise). A comprehensive cardiovascular assessment was conducted during the tests. Resting cardiovascular activity (baseline values) was also assessed. Follow-up resting cardiovascular parameters were measured in the laboratory 2 1/2 years later. RESULTS: Cardiovascular stress responses were predictive of cardiovascular follow-up resting levels 2 1/2 years later. Multiple regression was used to evaluate the independent predictive power of stress responses after controlling for traditional risk factors. Follow-up resting systolic blood pressure (SBP) was predicted by the SBP response to postural change and treadmill exercise. Follow-up resting diastolic blood pressure (DBP) was predicted by the DBP response during treadmill exercise, particularly for blacks. The follow-up resting heart rate was predicted by the heart rate response to the forehead cold pressor and treadmill exercise. CONCLUSION: These results show that in very young children, stress responses are predictive of resting cardiovascular functioning 2 1/2 years later. Further developmental and longitudinal investigations will determine whether such responses are predictive of later preclinical manifestations of cardiovascular disease. If so, incorporation of stress testing in a standardized risk identification protocol might aid the design and practice of cardiovascular preventive medicine.

Analysis of Variance↗
PubMed1996

Intraductal mucin-hypersecreting neoplasm "mucinous ductal ectasia": endoscopic recognition and management.

OBJECTIVES: Intraductal mucin-hypersecreting neoplasm (IMHN), also termed mucinous ductal ectasia, is a rare disorder of the pancreas characterized by distension of the pancreatic duct with mucus. This study attempted to clarify the clinical, radiographic, histological, and treatment approaches to this entity. METHODS: The medical records, radiological imaging studies, and pathology specimens of eight patients with IMHN seen during a 3-yr period were reviewed. The diagnosis of IMHN was established by findings during ERCP, which included mucin plugging of the papilla, mucin extrusion from the papillary orifice after intraductal injection of contrast medium, mucinous filling defects in the main pancreatic duct, and dilated main and branch pancreatic ducts in the absence of obstructing ductal strictures. RESULTS: All patients presented with an initial clinical diagnosis of acute or chronic pancreatitis, suspected cystic neoplasm, or biliary obstruction. Noninvasive imaging studies such as transabdominal ultrasonography or CT and laboratory evaluation did not seem to help in defining the disease. Five patients underwent Whipple resection; pathology included papillary ductal hyperplasia in one, dysplastic mucinous epithelium in two, and mucinous cystadenocarcinoma in two. All five patients had associated histological evidence of chronic pancreatitis. All patients are alive and well after 21-53 months without evidence of residual disease. CONCLUSIONS: IMHN has a wide spectrum of clinical, radiological, and histological features. The indolent biologic behavior and favorable prognosis of IMHN suggest that it is one of the most curable forms of pancreatic malignancy.

Adult↗
PubMed1996

Nifedipine-associated gingival overgrowth: a survey of the literature and report of four cases.

A survey of the literature indicates that calcium channel-blocking medications are used for an ever-increasing number of medical problems. Their use may result in gingival overgrowth that can be of concern to the patient and dentist. Four cases are presented that illustrate several relevant points: (1) histologic examination may reveal factors overlooked in the medical history; (2) the condition exists in a variety of clinical manifestations; (3) the level of plaque control maintained by the patient is important to the management of the condition; and (4) responses vary to different approaches to treatment, including changes in medication, as well as nonsurgical and surgical therapies.

Adult↗
PubMed1996

Moderators of ethnic differences in vasoconstrictive reactivity in youth.

Three hundred and forty-one children (170 males and 171 females: 155 whites and 186 blacks) with a mean age of 11.2 years completed laboratory stressors of forehead cold and a video game. Impedance cardiography was used to assess total peripheral resistance indexed by body surface area (TPRI) at rest and during the stressors. Black youths exhibited greater TPRI and mean arterial pressure (MAP) reactivity to both stressors. It was hypothesized that anthropometric, demographic, lifestyle, and psychosocial variables might partially account for ethnicity differences in vasoconstrictive reactivity. Black youths' higher resting MAP and TPRI and greater MAP and TPRI reactivity to forehead cold were accounted for by anthropometric characteristics, physical activity, sedentary behavior (i.e., TV viewing) and family cohesion. The ethnic differences in TPRI and MAP video game reactivity were not accounted for by the various parameters.

Black or African American↗
PubMed1995

Rho protein regulates tight junctions and perijunctional actin organization in polarized epithelia.

The rho family of GTP-binding proteins regulates actin filament organization. In unpolarized mammalian cells, rho proteins regulate the assembly of actin-containing stress fibers at the cell-matrix interface. Polarized epithelial cells, in contrast, are tall and cylindrical with well developed intercellular tight junctions that permit them to behave as biologic barriers. We report that rho regulates filamentous actin organization preferentially in the apical pole of polarized intestinal epithelial cells and, in so doing, influences the organization and permeability of the associated apical tight junctions. Thus, barrier function, which is an essential characteristic of columnar epithelia, is regulated by rho.

ADP Ribose Transferases↗
PubMed1995

Job status and high-effort coping influence work blood pressure in women and blacks.

Work-related stress has been associated with an increased risk of hypertension and more severe cardiovascular problems in white men but has been less studied in women and black men. To determine whether the trait of high-effort coping (John Henryism) was related to higher blood pressure during work and laboratory challenges, we studied a biracial sample of 72 men and 71 women working full time outside the home who underwent ambulatory blood pressure monitoring for one 8-hour workday. This was followed by laboratory monitoring of blood pressure during resting baseline and five brief stressors. Women who were high-effort copers and had high status jobs had higher diastolic pressures at work and in the lab than other women; their pressure levels did not differ from those of men, but other women had lower pressures than men. In blacks, the same combination of high-effort coping plus high job status was similarly associated with high work and laboratory diastolic pressure, as well as higher work systolic pressure. The trait of high-effort coping was observed in the large majority (71%) of the women and blacks who had achieved high status jobs but was seen in a minority (36%) of white men with high status jobs and was unrelated to increased blood pressure in the latter group.

Adaptation, Psychological↗
PubMed1995

Hemodynamic responses during psychological stress: implications for studying disease processes.

Investigation of the physiological correlates of psychological stress is of interest in relation to the putative impact of stress in the etiology of cardiovascular disease. Although the assessment of blood pressure and heart rate responses to psychological stress has been very informative, the addition of cardiac output measurement has added a further dimension to this research field. In recent studies, a more complete hemodynamic picture of the stress response has been documented in terms of cardiac output and systemic vascular resistance components of blood pressure changes. Different stressors have been shown to produce similar blood pressure increases due to quite different hemodynamic mechanisms. Furthermore, when faced with the same stressor, different individuals may exhibit pressor responses that are very different hemodynamically. There is growing evidence that these hemodynamic response patterns to psychological stress are stable individual traits. Response stability is a prerequisite for considering how stress-related hemodynamic changes may be implicated in the pathophysiology of cardiovascular diseases. Observations that hemodynamic response patterns in individuals at higher risk for the development of hypertension differ from those of lower risk individuals show that specific patterns of hemodynamic response are associated with disease processes. Although it is as yet unclear whether they represent markers or mechanisms. Overall. hemodynamic studies appear to he helping to refine our understanding of how stress can impact cardiovascular disease processes.

Journal Article↗