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Biomedical subjects

R Carroll

Publications and source records attributed to R Carroll.

At least 19 recordsLinked to original sources
PubMed2003

Unusual electrocardiographic presentation of an isolated right ventricular myocardial infarction secondary to thrombotic occlusion of a non-dominant right coronary artery--a case report and brief review of literature.

Isolated right ventricular infarction is an extremely rare phenomenon. Its electrocardiographic (ECG) features may be misinterpreted or even missed if not suspected. A case of an isolated right ventricular myocardial infarction is presented, recognized by ST-segment elevation in a single precordial lead, such as V1, aided thereafter by right precordial ECG changes. Immediate coronary angiography revealed proximal occlusion of a small non-dominant right coronary artery. Coronary intervention as well as infusion of intravenous normal saline solution and pressor agent for hypotension provided symptomatic relief, and subsequent recovery from this potentially life-threatening, but rare condition. Routine 12-lead ECG done approximately 12 hours after the admission showed extension of ST segment elevation from V1 trough V3 without any ST-segment elevation in inferior leads. This case demonstrates that there might be a very unusual ECG appearance in the setting of an isolated right ventricular myocardial infarction and can be missed if not immediately suspected. Isolated right ventricular myocardial infarction may be difficult to recognize, requiring both a high index of clinical suspicion for its presence, as well as careful evaluation of unusual ECG features of the disease entity.

Aged↗
PubMed2001

Pituitary tumorigenesis and hPit-1 cells.

Despite decades of clinical data verifying the success of therapeutic approaches to human pituitary tumors, a significant number of tumors progress and can be life-threatening. The development of better therapeutic strategies for pituitary tumors is complicated by the relative scarcity of human pituitary material for basic experimentation. Human pituitary tissue was used to derive cell cultures, and a cell line, hPIT-1. Molecular and functional analyses were used to further characterize the cells as human pituitary explants in vitro. Functional analyses of the cell cultures indicated that the cells were tumorigenic and of human folliculostellate origin. hPit-1 cells revealed numerous abnormalities of ploidy. Molecular analyses indicated the absence of expression of the following pituitary hormones or hormone subunits by this culture: growth hormone, prolactin, ACTH, FSHbeta, LHbeta, THbeta, and p-glycoprotein. By contrast, the cells expressed uniformly high levels of human follistatin mRNA. Finally, the cells are moderately tumorigenic in immune-deficient mice. Although the precise molecular genetic mechanisms for tumorigenesis in the established cell culture are unknown, the cells serve as a future resource in the study of pituitary tumor initiation, progression, and response to therapy.

Adult↗
PubMed2001

Severe defect in proglucagon processing in islet A-cells of prohormone convertase 2 null mice.

Mice homozygous for a deletion in the gene encoding prohormone convertase 2 (PC2) are generally healthy but have mild hypoglycemia and flat glucose-tolerance curves. Their islets show marked alpha (A)-cell hyperplasia, suggesting a possible defect in glucagon processing (Furuta, M., Yano, H., Zhou, A., Rouille, Y., Holst, J., Carroll, R., Ravazzola, M., Orci, L., Furuta, H., and Steiner, D. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 6646-6651). In this report we have examined the biosynthesis and processing of proglucagon in isolated islets from these mice via pulse-chase labeling and find that proglucagon undergoes essentially no processing in chase periods up to 8 h in duration. Only a small percent of cleavage at the sensitive interdomain site (residues 71 and 72) appears to occur. These observations thus conclusively demonstrate the essentiality of PC2 for the production of glucagon in the islet A-cells. Ultrastructural and immunocytochemical studies indicate the presence of large amounts of proglucagon in atypical appearing secretory granules in the hyperplastic and hypertrophic A-cells, along with morphological evidence of high rates of proglucagon secretion in PC2 null islets. These findings provide strong evidence that active glucagon is required to maintain normal blood glucose levels, counterbalancing the action of insulin at all times.

Animals↗
PubMed2001

Mitochondrial K(ATP) channel opening protects a human atrial-derived cell line by a mechanism involving free radical generation.

OBJECTIVES: The mechanism by which the mitochondrial K(ATP) channel openers confer protection against ischemia/reperfusion injury is debated. Evidence suggests that rather than solely being an end effector, opening of these channels may act by a trigger mechanism. We examined the effects of the mitochondrial K(ATP) channel opener, diazoxide on parameters of mitochondrial function with specific reference to reactive oxygen species (ROS) generation in a human atrial derived cell line model of simulated ischemia/reperfusion (LSI/R). METHODS AND RESULTS: Propidium iodide (PI) exclusion was used to assess survival. Diazoxide treatment conferred protection against LSI/R (13.9+/-0.9% vs. 36.9+/-4.5% controls) that was abolished by pre-treatment with the mitoK(ATP) channel blocker, 5-hydroxydecanoate (5-HD) (33.3+/-3.6%) and with the free radical scavenger, 2-mercaptopropionylglycine (MPG) (29+/-4.0%). Diazoxide caused increased oxidation of the ROS probe, reduced mitotracker orange (1.3 vs. 1.0 arbitrary units for control; P<0.01 vs. control) that was abrogated by either 5-HD or MPG (1.07 and 1.07 arbitrary units, respectively). At the same time there was no change in orange fluorescent signal from the membrane potential sensitive probe, JC-1 indicating no change in mitochondrial membrane potential. Changes in light scattering, reflecting changes in mitochondrial volume, occurred during treatment with diazoxide. CONCLUSION: These results demonstrate for the first time that the mitoK(ATP) channel opener diazoxide can act as a trigger of preconditioning by a mechanism involving mitochondrial swelling and the generation of ROS.

Analysis of Variance↗
PubMed2001

Peroxisome proliferator-activated receptor-alpha ligands inhibit cardiac lipoprotein lipase activity.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate gene expression of lipoprotein lipase (LPL) in liver and adipose tissue. We examined the direct effect of PPAR-alpha ligands on LPL catalytic activity in cultured cardiomyocytes from adult rat heart. After overnight culture (16 h), 1 microM Wy-14643 and 10 microM BM-17.0744 decreased total cellular LPL activity to approximately 50% of control with no change in enzyme synthesis or mass; as a consequence, PPAR-alpha activation produced a significant decrease in LPL specific activity (mU/ng LPL protein). Wy-14643 and BM-17.0744 also reduced heparin-releasable LPL activity and mass in the culture medium. Inhibition of LPL activity by Wy-14643 did not reduce the ability of insulin plus dexamethasone to stimulate cellular and heparin-releasable LPL activities. A similar inhibitory effect on cellular and heparin-releasable LPL activity was observed when cardiomyocytes were cultured with 60 microM linoleic acid. In conclusion, two different PPAR-alpha ligands (Wy-14643 and BM-17.0744) inhibited cellular LPL activity in cultured cardiomyocytes by a posttranscriptional and posttranslational mechanism.

Animals↗
PubMed2000

Distinct roles for ionotropic and metabotropic glutamate receptors in the maturation of excitatory synapses.

We used the single-cell culture preparation to study the role of activity in the development of glutamatergic synapses in vitro. Rat hippocampal cells grown in isolation on glial islands formed functional autaptic connections and continued to elaborate new synapses throughout the 2 week investigation, resulting in increases in both the evoked AMPA receptor (AMPAR) and NMDA receptor (NMDAR) components of the EPSC. Synaptogenesis was not prevented by chronic blockade of sodium channels or all of the known glutamate receptors. Analysis of miniature EPSCs revealed that AMPAR quantal size doubled over time in vitro whereas NMDAR quantal size remained constant. However, the proportion of synaptic responses mediated only by NMDARs increased over time in vitro. The increase in AMPAR quantal size was prevented by TTX and ionotropic glutamate receptor antagonists, whereas the increase in the proportion of NMDAR-only synapses was prevented by metabotropic glutamate receptor antagonists. Notably, chronic NMDAR blockade incubation did not block the formation of the AMPAR EPSC, indicating that NMDAR-dependent plasticity is not necessary for the onset of AMPAR synaptic transmission in this system. We conclude that action potentials and ionotropic glutamate receptor activation are necessary for the developmental increase in AMPAR quantal size and that metabotropic glutamate receptor activation is required for the production of NMDAR-only synapses, but none of these is essential for synapse formation.

Animals↗
PubMed2000

Delayed cardioprotection in a human cardiomyocyte-derived cell line: the role of adenosine, p38MAP kinase and mitochondrial KATP.

UNLABELLED: Evidence of delayed preconditioning (PC) in man is limited. Adenosine is proposed as a trigger via action on the A1 receptor in many species and the mitochondrial KATP channel is a likely end effector. We examined the ability of a brief, simulated ischemic episode on day one to provide delayed cardioprotection against lethal, simulated ischemia on day two in a human cardiac cell line with reference to the role of adenosine, the p38MAP kinase signalling pathway and mitochondrial KATP channel. RESULTS: PC and adenosine administered on day 1 protected against cell death on day 2 as measured by LDH release and propidium iodide (PI) exclusion: (%LDH release: PC: 12.1 +/- 1.1%, ADO: 11.9 +/- 2.0% vs control: 36.4 +/- 1.1%; %PI positive: PC: 14.6 +/- 1.4%, ADO: 17.9 +/- 2.0% vs control: 34.4 +/- 2.0% respectively). This protection is abolished by treatment with SB203580 prior to the protective stimulus on day 1: [PC + SB (%LDH release 28.6 +/- 2.8%; %PI positive 34.7 +/- 2.2%) and ADO + SB (%LDH release 25.3 +/- 2.9%; %PI positive 33.7 +/- 7.3)]. Similarly 5-hydroxydecanoate abolished protection, when given immediately prior to lethal simulated ischemia on day 2: [PC + 5-HD; (%LDH release 31.9 +/- 4.8%; %PI positive 29.5 +/- 2.0%) and ADO + 5-HD (%LDH release 36.9 +/- 4.0%; %PI positive 34.8 +/- 2%)]. CONCLUSION: In this model delayed PC can be mimicked by adenosine and involves the p38MAP kinase pathway and the mitochondrial KATP channel.

Adenosine↗
PubMed2000

Parathyroid hormone-related protein and its receptor in human glial tumors.

OBJECTIVE: Parathyroid hormone-related protein (PTHrP) and its mRNA have been found to be expressed in a variety of human tumors including breast, prostate, colon, lung, renal and ovarian cancers. The purpose of this study is to evaluate the expression of PTH/PTHrP receptor and ligand in human glial tumors. METHODS: We examined the coexpression of PTH/PTHrP receptor and ligand in 73 glial tumors of different histological grades and 4 nonneoplastic human brain specimens and three glioblastoma cell lines, by using Western Blot analysis and immunohistochemical analysis. RESULTS: PTHrP and PTH/PTHrP receptors were shown in the neurons, reactive astrocytes and the endothelial cells of normal brain tissue as well as tumor cells, reactive astrocytes and vasculature of nonneoplastic tissue. They were expressed at higher levels in pure astrocytic tumors as compared to tumors with oligodendroglial components. CONCLUSION: PTH/PTHrP receptor and PTHrP ligand are co-expressed in human glial tumors. There increased expression suggests an autocrine and/or paracrine loop may exist.

Adult↗
PubMed2000

SB 203580, a mitogen-activated protein kinase inhibitor, abolishes resistance to myocardial infarction induced by heat stress.

Heat stress (HS) is known to confer protection against ischemia-reperfusion injury, including mechanical dysfunction and myocardial necrosis. However, the mechanisms involved in this cardioprotection are yet to be elucidated. Mitogen-activated protein (MAP) kinase cascades have been demonstrated to be involved in cellular response to different stresses. In particular, p38 MAP kinase is known to be activated by HS. Therefore, we investigated the implication of this kinase in HS-induced resistance to myocardial infarction, in the isolated rat heart model, using SB 203580 (SB) to selectively inhibit p38 MAP kinase. Rats were treated with SB (2.83 mg/kg, i.p.) or vehicle (1% DMSO in saline, i.p.) before they were either heat stressed (42 degrees C for 15 minutes) or sham anesthetized. Their hearts were isolated 24 hours later, retrogradely perfused, and subjected to a 35-minute occlusion of the left coronary artery followed by 120 minutes of reperfusion. The infarct-to-risk ratio was significantly reduced in HS (16.9 +/- 2.0%) compared with sham (41.6 +/- 2.5%) hearts. This reduction in infarct size was abolished in the SB 203580-treated group (37.8 +/- 1.9% in HS + SB vs. 42.0 +/- 1.9% in sham + SB). Risk zones were similar between experimental groups. Western blot analysis of the myocardial HSP72 showed an HS-induced increase of this protein, which was not modified by the p38 MAP kinase inhibitor, SB 203580. We conclude that activation of p38 MAP kinase appears to play a role in the functional cardioprotection associated with the heat stress response, which seems to be unrelated to the HSP72 level. Further investigations are required to elucidate the precise role of the p38 MAP kinase and heat stress proteins in this adaptative response.

Animals↗
PubMed2000

Regulation of secretion of PTHrP by Ca(2+)-sensing receptor in human astrocytes, astrocytomas, and meningiomas.

Parathyroid hormone-related protein (PTHrP) is the major mediator of the humoral hypercalcemia of malignancy and of malignant osteolysis associated with skeletal metastases of common epithelial cancers. PTHrP secretion is regulated by the extracellular calcium concentration ([Ca(2+)](o)) in several types of normal and malignant cells. Because the [Ca(2+)](o)-sensing receptor (CaR) is a key mediator of [Ca(2+)](o)-regulated hormone secretion [e.g., of parathyroid hormone (PTH) by parathyroid chief cells], we investigated the expression of the CaR and PTHrP in normal and neoplastic glial cells and studied the effects of [Ca(2+)](o) on PTHrP secretion. Our results show that primary embryonic human astrocytes (HPA) express CaR mRNA and protein as detected by RT-PCR and Western analysis, respectively. Furthermore, astrocytomas and meningiomas also express the CaR at similar levels as assessed by RT-PCR and Northern and Western blot analyses. HPA and astrocytomas express transcripts encoding all three known isoforms of PTHrP [PTHrP(139), PTHrP(141), and PTHrP(173), comprising 139, 141, and 173 predicted amino acid residues, respectively] as assessed by RT-PCR, whereas meningiomas express only the first two of these. Finally, elevated levels of [Ca(2+)](o) and other polycationic CaR agonists dose dependently stimulate PTHrP secretion from HPA, astrocytomas, and meningiomas, although both basal and high [Ca(2+)](o)-stimulated rates of PTHrP secretion are approximately 2. 5-fold higher in HPA than in the glial tumors studied here. Therefore, our results show that HPA, astrocytomas, and meningiomas express both the CaR and PTHrP and that CaR agonists stimulate PTHrP secretion.

Astrocytes↗
PubMed2000

Effectiveness of lateral slide exercise in an anterior cruciate ligament reconstruction rehabilitation home exercise program.

STUDY DESIGN: Two-group repeated measures design using a sample of convenience of subjects with anterior cruciate ligament (ACL) reconstructive surgery. OBJECTIVES: To determine the effect of incorporating one specific weight-bearing exercise (lateral slide exercise using a slide board) into an ACL reconstruction home exercise program. BACKGROUND: Reduced clinic visits have increased the importance of home exercise programs in knee ligament reconstruction rehabilitation. Few studies have been conducted to test the efficacy of specific exercises as part of a home-based treatment program on subjects who have undergone ACL reconstruction. METHODS AND MEASURES: Fourteen subjects who underwent patella tendon autograft reconstruction on one of their ACLs were studied. Testing consisted of the following 4 measurements: peak isometric knee extension torque, peak isometric knee flexion torque, maximum lateral step height, and lateral step-up repetitions to fatigue. Subjects were pretested at 8 weeks after surgery and were randomly placed into either a control or experimental group. The postsurgical rehabilitation was similar for both groups, except the experimental group incorporated lateral slide exercise into their home exercise program. All subjects were re-evaluated 14 weeks after surgery. RESULTS: A 2-way repeated measure ANOVA (group by test session), and posthoc testing revealed significant improvements in the slide group for quadricep strength (101.9 +/- 31.3 N m to 140.5 +/- 31.3 N m of torque), while the control group showed no significant increase (125.1 +/- 61.7 N m to 125.8 +/- 45.1 N m of torque). Lateral step height also improved in the slide group (from 22.9 +/- 5.3 cm to 28.7 +/- 5.6 cm), while the control group showed no increase (20.0 +/- 4.5 cm to 20.7 +/- 3.4 cm). Both groups increased in lateral step-up repetitions to fatigue. CONCLUSION: Including lateral slide exercise in a home exercise program after ACL reconstruction appears to improve knee extension strength.

Adult↗