tbuckley/cabot-search huggingface dataset:
Connexin43 and Connexin45 Form Heteromeric Gap Junction Channels in Which Individual Components Determine Permeability and Regulation
Authors: Agustin D. Martinez, Volodya Hayrapetyan, Alonso P. Moreno, Eric C. Beyer
Journal: Circulation Research (2002)

Abstract — Two gap junction proteins, connexin43 (Cx43) and connexin45 (Cx45), are coexpressed in many cardiac and other cells. Homomeric channels formed by these proteins differ in unitary conductance, permeability, and regulation. We sought to determine the ability of Cx43 and Cx45 to oligomerize with each other to form heteromeric gap junction channels and to determine the functional and regulatory properties of these heteromeric channels. HeLa cells were transfected with Cx45 or (His) 6 -tagged Cx43 or sequentially transfected with both connexins. Immunoblots verified production of the transfected connexins, and immunofluorescence demonstrated that they were colocalized in the HeLa-Cx43(His) 6 /Cx45 cells. Connexons were solubilized from HeLa-Cx43(His) 6 /Cx45 cells by using Triton X-100 and were applied to a Ni 2+ -NTA column, which binds the His 6 sequence. Cx45 was coeluted from the column with Cx43(His) 6 , demonstrating that some hemichannels contain both connexins. Single-channel recordings showed that the HeLa-Cx43(His) 6 /Cx45 cells exhibited single-channel conductances that were not observed in cells expressing either connexin alone. Dye-coupling experiments showed that HeLa-Cx43(His) 6 cells readily passed Lucifer yellow and N -(2-aminoethyl)biotinamide hydrochloride (neurobiotin); in contrast, HeLa-Cx45 and HeLa-Cx43(His) 6 /Cx45 cells showed extensive intercellular passage of neurobiotin but little coupling with Lucifer yellow. Treatment with the protein kinase C activator 12- O -tetradecanoylphorbol 13-acetate reduced junctional conductance in cells expressing Cx43, Cx45, or both connexins, but it reduced the extent of neurobiotin transfer only in HeLa-Cx43(His) 6 and HeLa-Cx43(His) 6 /Cx45 cells but not in the HeLa-Cx45 cells. Thus, biochemical and electrophysiological evidence suggests that Cx43 and Cx45 extensively mix to form heteromeric channels; however, individual connexin components dominate aspects of the physiological behavior of these channels.
Coronary Stents
Authors: Eugene V. Pomerantsev, Yoshiki Kobayashi, Peter J. Fitzgerald, Eberhard Grube, William J. Sanders, Edwin L. Alderman, Stephen N. Oesterle, Paul G. Yock, Simon H. Stertzer
Journal: Circulation (1998)

Background —The validity of quantitative coronary angiography (QCA) after stent placement has been questioned because the optical density of a metallic stent, added to the density of a contrast-filled lumen, could affect border definition. Methods and Results —We deployed 3.0- and 4.0-mm Palmaz-Schatz, Wiktor, Multilink, NIR, and InStent stents in precision-cast phantoms. Central lumens of 2.0 mm were created. There was no difference between the “true” diameters of any stented lumen by both QCA and quantitative ultrasonic (QCU) measurement poststenting. QCA systematic error (SE) varied from 0.01 for the Wiktor stents to 0.14 mm for the Palmaz-Schatz stents; the random error (RE) was 0.03 to 0.14 mm. QCU SE varied from 0.05 to 0.11 mm, and RE ranged from 0.01 to 0.07 mm. At the next stage, 4.0-mm Wiktor and Palmaz-Schatz stents were deployed into the phantom lumens; 1.5-, 2.0-, 2.5- and 3.0-mm lumens were created inside the stents. QCA and QCU measurements of 1.5- to 2.5-mm residual lumens were overestimated by 0.1 to 0.3 mm. In the 3.0-mm residual lumen within the Wiktor stent, QCA underestimated the luminal size by −0.1 mm. There was no QCA inaccuracy for a 3.0-mm lumen within the Palmaz-Schatz stent. In patients, in 25 stented segments in both the Palmaz-Schatz and Wiktor groups, there was no difference between QCA and QCU diameters. Conclusions —QCU is sufficiently precise for the assessment of the coronary lumen after stenting. QCA can be used as an accurate method of poststent assessment, except when a very mild recurrence within a highly opaque stent is measured. In that instance, QCA may underestimate the luminal diameter.
Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial
Authors: Stefan Janssens, Christophe Dubois, Jan Bogaert, Koen Theunissen, Christophe Deroose, Walter Desmet, Maria Kalantzi, Lieven Herbots, Peter Sinnaeve, Joseph Dens, Johan Maertens, Frank Rademakers, Steven Dymarkowski, Olivier Gheysens, Johan Van Cleemput, Guy Bormans, Johan Nuyts, Ann Belmans, Luc Mortelmans, Marc Boogaerts, Frans Van de Werf
Journal: The Lancet (2006)
Assessment of tidal breathing parameters in infants with cystic fibrosis
Authors: S.C. Ranganathan, I. Goetz, A-F. Hoo, S. Lum, R. Castle, J. Stocks
Journal: European Respiratory Journal (2003)

Simple methods are needed to assess lung function in infants with cystic fibrosis (CF). This study determined the relationship between simple measurements obtained from tidal breathing with those from more complicated forced expiratory manoeuvres. Healthy infants and infants with CF were recruited from two maternity units and five specialist CF hospitals, respectively. Respiratory rate, tidal volume, minute ventilation and the tidal breathing ratio (TPTEF:TE) were measured in sedated infants and compared with forced expiratory volume in 0.4 seconds (FEV0.4) measured by the raised volume technique. Altogether, 95 healthy infants and 47 infants with CF of similar age, sex, ethnicity and proportion exposed to maternal smoking were recruited. There was no difference in TPTEF:TE and tidal volume between healthy infants and those with CF. Minute ventilation was significantly greater in infants with CF due to a mean (95% confidence interval) increase in respiratory rate of 5.8 (3.2-8.4) min(-1). Thirteen (28%) infants with CF had a respiratory rate elevated by >2 SD. However, no association between respiratory rate and FEV0.4 could be identified. Tidal breathing ratio was not useful in identifying diminished airway function in infants with cystic fibrosis. An elevated respiratory rate may be due in part to ventilation heterogeneity but is poorly predictive of diminished airway function measured by forced expiration.
An elitist naturalistic fallacy and the automatic-controlled continuum
Authors: Sandra L. Schneider
Journal: Behavioral and Brain Sciences (2000)

Although a focus on individual differences can help resolve issues concerning performance errors and computational complexity, the understanding/acceptance axiom is inadequate for establishing which decision norms are most appropriate. The contribution of experience to automatic and controlled processes suggests difficulties in attributing interactional intelligence to goals of evolutionary rationality and analytic intelligence to goals of instrumental rationality.
Eotaxin and monocyte chemoattractant protein-1 in chronic eosinophilic pneumonia
Authors: H. Tateno, H. Nakamura, N. Minematsu, K. Amakawa, T. Terashima, S. Fujishima, A.D. Luster, C.M. Lilly, K. Yamaguchi
Journal: European Respiratory Journal (2001)

Chronic eosinophilic pneumonia (CEP) is characterized by chronic or recurrent pulmonary infiltrates with eosinophils, but the precise mechanism of eosinophil accumulation has not been fully elucidated. Eotaxin is one of the CC chemokines that selectively recruits eosinophils and contributes to the pathogenesis of allergic airway diseases including asthma, but its roles in pathogenesis of CEP have not been fully elucidated. The authors measured concentrations of eotaxin and other CC chemokines, monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted, macrophage inflammatory protein-1α, and the eosinophil activating Th2 cytokine interleukin (IL)-5 in bronchoalveolar lavage (BAL) fluid from CEP patients (n=11), and compared these concentrations with those from control subjects (n=6). The eotaxin (904±203 versus 29±7 pg·mL −1 , p=0.0001), MCP-1 (194±57 versus 15±2 pg·mL −1 , p&lt;0.05), and IL-5 (7.8±2.0 versus 2.7±0.6 pg·mL −1 , p&lt;0.05) levels were significantly higher for cases with CEP in comparison to those serving as controls. Proportions of eosinophil and lymphocyte counts were greater in BAL fluid from CEP patients. Eotaxin and IL-5 levels correlated with the proportion of eosinophils in BAL fluid from CEP patients. MCP-1 correlated with the relative lymphocyte numbers. In short, eotaxin, interleukin-5, and monocyte chemoattractant protein-1 levels were higher in the BAL fluid of CEP patients and these levels may contribute to eosinophil and lymphocyte recruitment and activation in the airways as found with this disorder.
Increased Therapeutic Index of Antineoplastic Drugs in Combination With Intracellular Histamine Antagonists
Authors: L. J. Brandes, F. S. LaBella, R. C. Warrington
Journal: JNCI Journal of the National Cancer Institute (1991)

L-Histidinol, a Protein synthesis inhibitor and structural analogue of L-histidine, has been demonstrated in chemotherapy-treated mice to be cytoprotective to normal stem cells but to enhance cytotoxicity to tumor cells. N, N -Diethy1–2-(4-(Phenylmethyl) Phenoxy)ethanamine. HCI (DPPE) is an antagonist of recently described micro-somal and nuclear intracellular histamine receptors implicated in the mediation of proliferation and modulation of prostaglandian synthesis. DPPE is cytotoxic to tumor cells in vitro and cytoprotective to the gut in vivo. Noting the similar pharmacologic profiles for histidinol and DPPE and the structural resemblance between histidinol and histamine, we tested 1) whether binding to intracellular histamine receptors may be important to the action of histidinol, 2) whether there exists a differential effect of DPPE and histidinol on proliferating normal and transformed or malignant cells, and 3) whether DPPE, like histidinol, protects host cells from the effects of chemotherapy while augmenting tumor cell kill in vivo. It was observed that histidinol does compete at intracellular histamine receptors in isolated microsomes and nuclei, but with significantly lower affinity than DPPE. Nevertheless, for each agent, potency at intracellular histamine receptors correlates with potency to inhibit DNA and protein synthesis, without cytotoxicity, in normal mitogen-stimulated murine lymphocytes and to kill transformed mouse lymphocytes or MCF-7 human breast cancer cells. As demonstrated previously for histidinol (1–2 g/kg), DPPE (4 mg/kg) protected murine bone marrow progenitors from doxorubicin or fluorouracil, while doses of 4–50 mg/kg significantly enhanced the antitumor activity of doxorubicin and daunorubicin in murine models of early cancer. One postulate to explain the effects of intracellular histamine receptor ligands is that intracellular histamine mediates DNA and protein synthesis, possibly through a downward modulation of growth-inhibitory prostaglandin levels. Antagonosm of the intracellular action of histamine at intracellular histamine receptors by DPPE or histidinol may result in differential perturbations of growth/eicosanoid metabolism in normal and malignant cells, thus forming the basis of a new approach to chemotherapy. [J Natl Cancer Inst 83:1329–1336, 1991]
Relative Influence of Acute Sodium and Volume Depletion on Aldosterone Secretion in Nephrectomized Man
Authors: ROBERT E. MCCAA, JOHN D. BOWER, CONNIE S. MCCAA
Journal: Circulation Research (1973)

Plasma aldosterone concentration can increase in anephric man during hemodialysis despite the lack of kidneys to produce renin. Because the metabolic clearance rate of aldosterone does not change during hemodialysis, aldosterone secretion must increase in response to sodium depletion, volume depletion, or both. This study was designed to determine the relative influence of sodium and volume depletion by ultrafiltration and hemodialysis on plasma aldosterone concentration in anephric man. Fluid (547 ml) was removed from 13 anephric subjects during 4 hours of ultrafiltration in the absence of hemodialysis. Plasma sodium and potassium concentration did not change during ultrafiltration, but total body sodium and potassium decreased. Plasma aldosterone concentration did not change significantly. Each subject was then hemodialyzed for 8 hours. In 5 subjects, an additional liter of fluid was removed without a significant change in plasma sodium concentration. Plasma aldosterone concentration also did not change in response to the reduction in fluid volume. In 8 subjects, an additional liter of fluid was removed, and plasma sodium concentration decreased from 138.5 to 130.0 mEq/liter. Plasma aldosterone concentration increased from 8.3 to 19.6 ng/100 ml plasma. Three additional anephric subjects were hemodialyzed against a dialysate containing 125.0 mEq sodium/liter for 8 hours. Plasma potassium and total body fluid volume were held constant. Plasma sodium concentration decreased from 138.5 to 125.0 mEq/liter, and plasma aldosterone concentration increased from 7.4 to 24.3 ng/100 ml plasma. These data indicate that acute sodium depletion by hemodialysis accompanied by decreased plasma sodium concentration without a change in plasma potassium concentration or fluid volume can stimulate aldosterone secretion independently of the renal renin-angiotensin system.
Trends in Opioid Prescribing by Race/Ethnicity for Patients Seeking Care in US Emergency Departments
Authors: Mark J. Pletcher, Stefan G. Kertesz, Michael A. Kohn, Ralph Gonzales
Journal: JAMA (2008)

jor public health problem in the United States 1 and a particular problem in emergency departments. 2Patients usually present to the emergency department when other medical help is not accessible or when symptoms, often including pain, are most severe.Emergency department visits therefore represent high-risk encounters in which assessment and treatment of pain should receive careful attention. 2acial and ethnic minority groups appear to be at particularly high risk of receiving inadequate treatment for pain in the emergency department.][8][9][10] Previous studies of the National Hospital Ambulatory Medical Care Survey (NHAMCS), a survey of US emergency department visits, have found national racial/ethnic differences in opioid prescribing for back pain and migraine (1997-1999) 6 and in provision of sedation for children with long-bone fractures (1992-1998). 11 In the 1990s, national attention focused on increasing awareness of the problem of inadequately treated pain. 1 Major campaigns undertaken by the Joint Commission on Accreditation of Healthcare Organizations ( JCAHO) 12 and the Veterans Health Administration 13 introduced standards for consistent monitoring and treatment of pain that have become important quality in-See also p 89 and Patient Page.
Use of different magnification factors to calculate radiological lung volumes.
Authors: A Bush, D M Denison
Journal: Thorax (1986)

In previous papers from this laboratory, Pierce et al described a method of measuring lung volumes from routine chest radiographs. The images on the film are magnified, and this was taken into account in their calculations. Their findings have recently been confirmed by Rodenstein et al. It is important to measure magnification accurately because errors in linear dimensions are cubed when volume is calculated. This paper describes two simple methods of improving the accuracy of the calculation of magnification.
A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial
Authors: Jian Hou, Xin Du, Jie Jin, Zhen Cai, Fangping Chen, Dao-bin Zhou, Li Yu, Xiaoyan Ke, Xiao Li, Depei Wu, Fanyi Meng, Huisheng Ai, Jingshan Zhang, Honeylet Wortman-Vayn, Nianhang Chen, Jay Mei, Jianmin Wang
Journal: Journal of Hematology & Oncology (2013)

There is an unmet need for treatment options in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Lenalidomide plus low-dose dexamethasone is effective and generally well tolerated in Caucasian RRMM patients, but no previous study has evaluated this regimen in Chinese RRMM patients. MM-021 is a phase 2, multicenter, single-arm open-label registration trial conducted to assess the efficacy, safety, and pharmacokinetics of lenalidomide plus low-dose dexamethasone in Chinese patients with RRMM. Patients with ≥1 prior antimyeloma therapy received lenalidomide plus low-dose dexamethasone until disease progression or discontinuation. Follow-up of surviving patients continued for ≥1 year after enrollment. The lenalidomide dose was 25 mg/day, and was adjusted according to baseline renal function. Most patients had advanced disease (85.6% had Durie- Salmon stage III) and were heavily pretreated (56.7% had received ≥4 prior regimens; 69.5% prior thalidomide and 63.1% prior bortezomib); 5.3% had immunoglobulin D (IgD) disease. The safety population comprised 199 eligible patients. In the efficacy population (n = 187), the disease control rate (at least stable disease) was 94.7%, and the overall response rate (at least partial response) was 47.6%. High response rates were also achieved in patients who had renal impairment and in those with IgD disease. After a median study follow-up of 15.2 months, the median response duration was 8.8 months (range, 0.4–18.8 months) and median progression-free survival was 8.3 months (95% CI 6.5–9.8). The most common grade 3–4 adverse events (AEs) were anemia (26.1%), neutropenia (25.1%), thrombocytopenia (14.6%), pneumonia (13.1%), leukopenia (9.5%), and decreased neutrophil count (8.5%). AEs led to lenalidomide dose reduction and/or interruption in 40.2% of patients, and treatment discontinuation in about 9% of patients. The pharmacokinetic profile of lenalidomide was similar to that reported in Caucasian and Japanese patients. Lenalidomide plus low-dose dexamethasone was associated with a high response rate and acceptable safety profile in heavily pretreated Chinese patients with RRMM, including those with renal impairment and IgD subtype. These findings highlight the clinical potential of this regimen in Chinese RRMM patients who have exhausted current treatment options. China State Food and Drug Administration (SFDA) registration (CTA reference numbers: 209 L10808; 209 L10809; 209 L10810; and 209 L10811) and ClinicalTrials.gov identifier: NCT01593410 .
Myocyte cellular hyperplasia and myocyte cellular hypertrophy contribute to chronic ventricular remodeling in coronary artery narrowing-induced cardiomyopathy in rats.
Authors: J Kajstura, X Zhang, K Reiss, E Szoke, P Li, C Lagrasta, W Cheng, Z Darzynkiewicz, G Olivetti, P Anversa
Journal: Circulation Research (1994)

To determine whether cardiac failure produced by chronic coronary artery stenosis was associated with the activation of myocyte cellular hyperplasia in the myocardium, the changes in number and size of left ventricular myocytes were measured in rats 3 months after surgery. The hypertrophied left ventricle was found to possess 44%, 32%, 49%, and 48% fewer mononucleated, binucleated, trinucleated, and tetranucleated myocytes, respectively. In contrast, the hypertrophied right ventricle contained 1.49 x 10(6) more myocytes as a result of a 2.1-fold, 1.4-fold, and 1.4-fold increase in mononucleated, binucleated, and tetranucleated myocytes. Myocyte cell volume was seen to increase 49% and 21% in left and right ventricular myocytes, respectively. The process of myocyte cellular hyperplasia in the right ventricular myocardium was accompanied by capillary proliferation, and these events were responsible for the parallel addition of newly formed cells and capillaries within the wall and mural thickening. Moreover, the in-series insertion of new myocytes contributed to right ventricular dilatation after coronary artery stenosis. In view of the fact that extensive myocardial damage and cell loss may have masked the phenomenon of myocyte cellular hyperplasia in the left ventricle, the presence of DNA synthesis in myocyte nuclei was evaluated at 3 days, 1 week, 2 weeks, 1 month, and 3 months after coronary artery stenosis. Bromodeoxyuridine (BrdU) labeling markedly increased in myocyte nuclei of both ventricles, reaching its peak at 1 and 2 weeks. BrdU labeling of nonmyocyte nuclei also increased but mostly at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
Low-dose total skin electron beam therapy as a debulking agent for cutaneous T-cell lymphoma: an open-label prospective phase II study
Authors: M.R. Kamstrup, L.M. Lindahl, R. Gniadecki, L. Iversen, L. Skov, P.M. Petersen, A. Loft, L. Specht
Journal: British Journal of Dermatology (2011)

Total skin electron beam therapy (TSEBT) is a powerful treatment for cutaneous T-cell lymphoma (CTCL). Based on the occurrence of relapses with low radiation doses, doses of 30-36Gy are commonly used but most patients still eventually relapse and repeat treatment courses are limited due to the cumulative toxicity. Complete response (CR) rates are about 60-90% for T2-4 stages with a 5-year relapse-free survival of 10-25% for stages IB-III.To evaluate prospectively the efficacy of low-dose TSEBT (10Gy) in terms of complete cutaneous response rate, overall response rate and response duration in CTCL.Ten patients with stage IB-IV mycosis fungoides (MF) were treated in an open-label manner with four fractions of TSEBT 1Gy weekly to a total skin dose of 10Gy. Treatment responses were assessed at 1 and 3months after treatment and subsequently at least every 6months for a total period of 2years or to disease relapse or progression.Patients achieved an overall response rate of 90%. The rate of CR or very good partial response (VGPR; <1% skin affected with patches/plaques) was 70%. The median response duration was 5·2months (range 83-469days) for CR and VGPR. Adverse effects were generally mild to moderate in severity.Low-dose TSEBT (10Gy) gave a satisfactory response rate and was well tolerated in patients with MF stage IB-IV. Future studies should determine if the combination of low-dose TSEBT with other agents could increase the rate of CR and response duration.
Intimomedial Interface Damage and Adventitial Inflammation Is Increased Beneath Disrupted Atherosclerosis in the Aorta
Authors: Pedro R. Moreno, K. Raman Purushothaman, Valentin Fuster, William N. O’Connor
Journal: Circulation (2002)

Atherosclerotic plaque progression is frequently accompanied by compensatory enlargement to preserve the lumen. These enlarging plaques develop features of vulnerability, however, leading to disruption and lumen obstruction. This complex transition from compensatory expansion to plaque disruption may not derive solely from progressive intimal disease. Concurrent changes at the intimomedial interface and within the tunica media and adventitia may play a role in plaque instability. We tested this hypothesis by investigating whether interface changes, including internal elastic lamina (IEL) rupture, and medial and adventitial changes, including inflammation, fibrosis, and atrophy, more frequently accompany disrupted than nondisrupted atherosclerotic plaques.Computerized planimetry and ocular micrometry were used for systematic quantification of intimal, medial, and adventitial histopathological features in 598 human aortic plaques according to the AHA classification. Disrupted plaques exhibited larger plaque and lipid pool areas (P=0.0001) and a higher incidence of rupture of the IEL (P=0.0001). Medial and adventitial inflammation (P=0.01), medial fibrosis (P=0.0001), and medial atrophy (P=0.0001) were also higher in disrupted plaques. Furthermore, medial thickness was reduced in disrupted plaques (P=0.0001). Logistic regression analysis identified rupture of the IEL as an independent predictor for fibrous cap disruption (P=0.0001).Compared with nondisrupted plaques, disrupted plaques have an increased incidence of IEL rupture, medial and adventitial inflammation, medial fibrosis, and medial atrophy. These intimomedial interface and adventitial changes may play a role in the natural history of complex atherosclerotic lesions. The interaction between medial and adventitial pathology and the intimal atherosclerotic process deserves further investigation.