tbuckley/cabot-search huggingface dataset:
Cell cycle dependence of ACE-2 explains downregulation in idiopathic pulmonary fibrosis
Authors: Bruce D. Uhal, MyTrang Dang, Vinh Dang, Roger Llatos, Esteban Cano, Amal Abdul-Hafez, Jonathan Markey, Christopher C. Piasecki, Maria Molina-Molina
Journal: European Respiratory Journal (2012)

Alveolar epithelial type II cells, a major source of angiotensin-converting enzyme (ACE)-2 in the adult lung, are normally quiescent but actively proliferate in lung fibrosis and downregulate this protective enzyme. It was, therefore, hypothesised that ACE-2 expression might be related to cell cycle progression. To test this hypothesis, ACE-2 mRNA levels, protein levels and enzymatic activity were examined in fibrotic human lungs and in the alveolar epithelial cell lines A549 and MLE-12 studied at postconfluent (quiescent) versus subconfluent (proliferating) densities. ACE-2 mRNA, immunoreactive protein and enzymatic activity were all high in quiescent cells, but were severely downregulated or absent in actively proliferating cells. Upregulation of the enzyme in cells that were progressing to quiescence was completely inhibited by the transcription blocker actinomycin D or by SP600125, an inhibitor of c-Jun N-terminal kinase (JNK). In lung biopsy specimens obtained from patients with idiopathic pulmonary fibrosis, immunoreactive enzyme was absent in alveolar epithelia that were positive for proliferation markers, but was robustly expressed in alveolar epithelia devoid of proliferation markers. These data explain the loss of ACE-2 in lung fibrosis and demonstrate cell cycle-dependent regulation of this protective enzyme by a JNK-mediated transcriptional mechanism.
Platelet microparticles and calcium homeostasis in acute coronary ischemias
Authors: John N. Katopodis, Luciano Kolodny, Wenche Jy, Lawrence L. Horstman, E.J. De Marchena, Jian G. Tao, Duncan H. Haynes, Yeon S. Ahn
Journal: American Journal of Hematology (1997)

Elevation of free cytoplasmic calcium is the common pathway of platelet activation, leading to shape change, shedding of platelet microparticles (PMP), aggregation, and secretion of internal granules, including expression of CD62p on the surface. Platelet activation is well documented in unstable angina (UA) and acute myocardial infarction (MI). We investigated the following markers of platelet activation in 55 patients undergoing coronary angiography for suspected CAD: free cytoplasmic calcium, [Ca2+]cyt, PMP, CD62p expression, and platelet/leukocyte (P/L) interaction. [CA2+]cyt was measured by Fluo-3 and the other measurements were by flow cytometry. Patients were classified into three groups: unstable angina (UA, n = 11), recent myocardial infarction (MI, n = 11), and patient controls (CTL, n = 33). Blood was drawn before infusion of heparin through femoral lines at the time of catheterization for assays. Results: (1) PMP values were significantly higher in both UA and MI than in CTL, P < 0.05. There was no difference between UA and MI. (2) P/L interaction was significantly elevated only in UA, P < 0.05. (3) CD62p expression on free platelets did not differ significantly between any of the three groups. (4) The resting [Ca2+]cyt, thrombin-induced CA2+ influx, and release of CA2+ from internal stores were all significantly higher in platelets from the combined patient group (UA + MI) than in the patient group, P < 0.001 Conclusions: Results on calcium hemostasis and PMP were significantly different in patients with acute coronary syndromes than those with stable angina or no coronay ischemia; this may reflect underlying pathophysiology of acute coronary ischemia. P/L interaction was higher only in the UA group, suggesting a role of leukocytes in the UA. Am. J. Hematol. 54:95–101, 1997 © 1997 Wiley-Liss, Inc.
Experimental glomerulonephritis in the isolated perfused rat kidney.
Authors: W G Couser, D R Steinmuller, M M Stilmant, D J Salant, L M Lowenstein
Journal: Journal of Clinical Investigation (1978)

The development of immune deposits on the subepithelial surface of the glomerular capillary wall was studied in isolated rat kidneys perfused at controlled perfusion pressure, pH, temperature, and flow rates with recirculating oxygenated perfusate containing bovine serum albumin (BSA) in buffer and sheep antibody to rat proximal tubular epithelial cell brush border antigen (Fx1A). Control kidney were perfused with equal concentrations of non-antibody immunoglobulin (Ig)G. Renal function was monitored by measuring inulin clearance, sodium reabsorption, and urine flow as well as BSA excretion and fractional clearance. Perfused kidneys were studied by light, immunofluorescence, and electron microscopy. All kidneys perfused with anti-Fx1A developed diffuse, finely granular deposits of IgG along the glomerular capillary wall by immunofluorescence. Electron microscopy revealed these deposits to be localized exclusively in the subepithelial space and slit pores. Similar deposits were produced in a nonrecirculating perfusion system, thereby excluding the formation of immune complexes in the perfusate caused by renal release of tubular antigen. Control kidneys perfused with nonantibody IgG did not develop glomerular immune deposits. Renal function and BSA excretion were the same in experimental and control kidneys. Glomerular deposits in antibody perfused kidneys were indistinguishable from deposits in rats injected with anti-Fx1A or immunized with Fx1A to produce autologous immune complex nephropathy. These studies demonstrate that subepithelial immune deposits can be produced in the isolated rat kidney by perfusion with specific antibody to Fx1A in the absence of circulating immune complexes. In this model deposits result from in situ complex formation rather than circulating immune complex deposition.
Good COP1 or bad COP1? In vivo veritas
Authors: Wenyi Wei, William G. Kaelin
Journal: Journal of Clinical Investigation (2011)

The evolutionarily conserved protein COP1 has been shown to operate as an E3 ubiquitin ligase complex, and a number of putative substrates have been identified, including the c-JUN oncoprotein and p53 tumor suppressor protein. New work by Migliorini and colleagues described in the current issue of JCI demonstrates that COP1 acts as a tumor suppressor in vivo and does so, at least in part, by promoting the destruction of c-JUN. These findings challenge the view that COP1 regulates p53 stability and call into question the wisdom of developing COP1 inhibitors as potential anticancer agents.
Medroxyprogesterone in postmenopausal females with partial upper airway obstruction during sleep
Authors: T. Saaresranta, P. Polo-Kantola, E. Rauhala, O. Polo
Journal: European Respiratory Journal (2001)

The aim of the present study was to evaluate the degree and duration of respiratory stimulation caused by medroxyprogesterone acetate (MPA), and compare the effect of MPA to that of nasal continuous positive airway pressure (nCPAP) in sleep-disordered breathing. Ten postmenopausal females with predominantly partial upper airway obstruction during sleep had an overnight sleep study at baseline, on the fourteenth day of treatment with MPA and after a 3-week washout period. Six subjects on nCPAP were also studied 3 months later. At baseline, the overnight mean±sd end-tidal pressure of carbon dioxide ( P et,CO 2 ) was 5.5±0.4 kPa the arterial oxygen saturation ( S a,O 2 ) 93.0±1.2%, S a,O 2 nadir 80.0±6.7%, and frequency of oxygen desaturation ⩾4% (ODI 4 ) per hour 2.2±1.3. MPA decreased P et,CO 2 by 0.8 kPa (14.5%, p&lt;0.001). After washout, the mean P et,CO 2 remained at 0.5 kPa (9.1%, p&lt;0.001) lower than at baseline. S a,O 2 did not change. P et,CO 2 was lower on MPA than on nCPAP (4.7±0.2 kPa versus 5.0±0.3 kPa; p=0.037) but S a,O 2 was similar. Apnoea/hypopnoea index tended to be lower on CPAP than on MPA. Medroxyprogesterone acetate at a daily dose of 60 mg improves ventilation in postmenopausal females with partial upper airway obstruction during sleep without compromising sleep. The ventilatory improvement is sustained for at least 3 weeks post-treatment. Medroxyprogesterone acetate was more efficient in decreasing the partial pressure of carbon dioxide but continuous positive airway pressure was superior in decreasing respiratory efforts.
Allogeneic Stem-Cell Transplantation May Overcome the Adverse Prognosis of Unmutated <i>VH</i> Gene in Patients With Chronic Lymphocytic Leukemia
Authors: Carol Moreno, Neus Villamor, Dolors Colomer, Jordi Esteve, Rodrigo Martino, Josep Nomdedéu, Francesc Bosch, Armando López-Guillermo, Elías Campo, Jorge Sierra, Emili Montserrat
Journal: Journal of Clinical Oncology (2005)

To investigate whether allogeneic stem-cell transplantation (allo-SCT) may overcome the negative impact of unmutated VH genes in the outcome of patients with chronic lymphocytic leukemia (CLL).We analyzed the outcome of patients who underwent SCT according to their VH mutational status.Thirty-four patients (14 allo-SCT and 20 autologous SCT [auto-SCT]) presented unmutated VH genes and 16 patients presented mutated VH genes (nine allo-SCT and seven auto-SCT). Tumoral burden pre-SCT was significantly higher in the allo-SCT patients independent of the VH mutational status. The risk of relapse was significantly higher after auto-SCT (5-year risk, 61%; 95% CI, 44% to 84%) than after allo-SCT (5-year risk 12%, 95% CI, 3% to 44%; P < .05). In the unmutated group, 13 of 20 auto-SCT and two of 14 allo-SCT patients experienced disease progression, with a risk of relapse at 5 years of 66% (95% CI, 48% to 93%) v 17% (95% CI, 5% to 60%), respectively (P = .01).These results show that allo-SCT may overcome the unfavorable effect of unmutated VH genes in patients with CLL.
Refining the Construct of Narcissistic Personality Disorder: Diagnostic Criteria and Subtypes
Authors: Eric Russ, Jonathan Shedler, Rebekah Bradley, Drew Westen
Journal: American Journal of Psychiatry (2008)

Narcissistic personality disorder has received relatively little empirical attention. This study was designed to provide an empirically valid and clinically rich portrait of narcissistic personality disorder and to identify subtypes of the disorder.A random national sample of psychiatrists and clinical psychologists (N=1,201) described a randomly selected current patient with personality pathology. Clinicians provided detailed psychological descriptions of the patients using the Shedler-Westen Assessment Procedure-II (SWAP-II), completed a checklist of axis II diagnostic criteria, and provided construct ratings for each axis II personality disorder. Descriptions of narcissistic patients based on both raw and standardized SWAP-II item scores were aggregated to identify, respectively, the most characteristic and the most distinctive features of narcissistic personality disorder.A total of 255 patients met DSM-IV criteria for narcissistic personality disorder based on the checklist and 122 based on the construct ratings; 101 patients met criteria by both methods. Q-factor analysis identified three subtypes of narcissistic personality disorder, which the authors labeled grandiose/malignant, fragile, and high-functioning/exhibitionistic. Core features of the disorder included interpersonal vulnerability and underlying emotional distress, along with anger, difficulty in regulating affect, and interpersonal competitiveness, features that are absent from the DSM-IV description of narcissistic personality disorder.These findings suggest that DSM-IV criteria for narcissistic personality disorder are too narrow, underemphasizing aspects of personality and inner experience that are empirically central to the disorder. The richer and more differentiated view of narcissistic personality disorder suggested by this study may have treatment implications and may help bridge the gap between empirically and clinically derived concepts of the disorder.
Human cystinuria-related transporter: Localization and functional characterization
Authors: Ken'Ichi Mizoguchi, Seok Ho Cha, Arthit Chairoungdua, Do Kyung Kim, Yasuhiro Shigeta, Hirotaka Matsuo, Jun-Ichi Fukushima, Yusuke Awa, Koichiro Akakura, Tomoyuki Goya, Haruo Ito, Hitoshi Endou, Yoshikatsu Kanai
Journal: Kidney International (2001)
A STUDY WITH THE ELECTROCARDIOGRAPH OF THE MODE OF DEATH OF THE HUMAN HEART
Authors: G. Canby Robinson
Journal: The Journal of Experimental Medicine (1912)

In four of the seven cases the ventricles remained active from one and a half to eighteen minutes after the electrocardiograms failed to show evidence of auricular activity. In two cases the auricles outlasted the ventricles and in one case only did the auricles and ventricles stop apparently at the same time. Complete dissociation occurred three times. Some delay in the conduction time was seen in five of the seven cases. In two cases the auricles ceased to beat before evidence of impaired conduction appeared. There was always marked slowing; the slowest independent ventricular rates varied from 13.6 to 47.0. The slowest rates at which the auricles beat regularly varied from 20 to 65 per minute. There was never evidence of auricular fibrillation, although in two cases the electrocardiograms give fairly conclusive evidence that ventricular fibrillation occurred. The ventricles reëstablished a regular rhythm after a short period of ventricular fibrillation in one case, while in the other but one ventricular contraction occurred after the appearance of fibrillation. Characteristic changes in the ventricular complex of the electrocardiograms occurred in all the records. They consisted of a gradual fusion of the R- and T-waves, forming, when the fusion was complete, a large rounded or peaked wave. In some cases the identity of the two waves was not entirely lost. In spite of the marked change in shape of the ventricular complexes, there was often but little change in their duration. In some cases the ventricular systole was shortened at the end, while in others it was prolonged. The change in the form of the ventricular electrical complex indicates that the course of the stimulus and the manner of the contraction of the muscle were abnormal. The fact that the R-wave became gradually prolonged suggests that the conduction of the stimulus through the ventricular walls became delayed as the heart died. The fact that after death there is a continuation of cardiac muscular activity sufficient to cause a difference in electrical potential between the two sides of the body does not necessarily mean that a ventricular systole in the sense of muscular shortening takes place. It has been observed experimentally that well defined electrical complexes may be caused by cardiac activity which cannot be seen or recorded graphically. As the duration of the ventricular complexes characteristic of the dying heart usually does not differ markedly from the duration of the complexes before clinical death, it seems probable that the entire musculature of the ventricles participates in the contraction; as definite shortening, or at least a marked change in duration, would be expected if only a part of the ventricular musculature participated in the activity which produced the complex.
Mutation of the endothelin-3 gene in the Waardenburg-Hirschsprung disease (Shah-Waardenburg syndrome)
Authors: Patrick Edery, Tania Attie, Jeanne Amiel, Anna Pelet, Charis Eng, Robert M.W. Hofstra, Helene Martelli, Christelle Bidaud, Arnold Munnich, Stanislas Lyonnet
Journal: Nature Genetics (1996)
Characterization of Human Atherosclerosis by Optical Coherence Tomography
Authors: Hiroshi Yabushita, Brett E. Bouma, Stuart L. Houser, H. Thomas Aretz, Ik-Kyung Jang, Kelly H. Schlendorf, Christopher R. Kauffman, Milen Shishkov, Dong-Heon Kang, Elkan F. Halpern, Guillermo J. Tearney
Journal: Circulation (2002)

Background— High-resolution visualization of atherosclerotic plaque morphology may be essential for identifying coronary plaques that cause acute coronary events. Optical coherence tomography (OCT) is an intravascular imaging modality capable of providing cross-sectional images of tissue with a resolution of 10 μm. To date, OCT imaging has not been investigated in sufficient detail to assess its accuracy for characterizing atherosclerotic plaques. The aim of this study was to establish objective OCT image criteria for atherosclerotic plaque characterization in vitro. Methods and Results— OCT images of 357 (diseased) atherosclerotic arterial segments obtained at autopsy were correlated with histology. OCT image criteria for 3 types of plaque were formulated by analysis of a subset (n=50) of arterial segments. OCT images of fibrous plaques were characterized by homogeneous, signal-rich regions; fibrocalcific plaques by well-delineated, signal-poor regions with sharp borders; and lipid-rich plaques by signal-poor regions with diffuse borders. Independent validation of these criteria by 2 OCT readers for the remaining segments (n=307) demonstrated a sensitivity and specificity ranging from 71% to 79% and 97% to 98% for fibrous plaques, 95% to 96% and 97% for fibrocalcific plaques, and 90% to 94% and 90% to 92% for lipid-rich plaques, respectively (overall agreement, κ=0.83 to 0.84). The interobserver and intraobserver reliabilities of OCT assessment were high (κ values of 0.88 and 0.91, respectively). Conclusions— Objective OCT criteria are highly sensitive and specific for characterizing different types of atherosclerotic plaques. These results represent an important step in validating this new intravascular imaging modality and will provide a basis for the interpretation of intracoronary OCT images obtained from patients.
Inflammatory Chemokine Transport and Presentation in HEV
Authors: Roger T. Palframan, Steffen Jung, Guiying Cheng, Wolfgang Weninger, Yi Luo, Martin Dorf, Dan R. Littman, Barrett J. Rollins, Hans Zweerink, Antal Rot, Ulrich H. von Andrian
Journal: The Journal of Experimental Medicine (2001)

Interstitial fluid is constantly drained into lymph nodes (LNs) via afferent lymph vessels. This conduit enables monocyte-derived macrophages and dendritic cells to access LNs from peripheral tissues. We show that during inflammation in the skin, a second recruitment pathway is evoked that recruits large numbers of blood-borne monocytes to LNs via high endothelial venules (HEVs). Inhibition of monocyte chemoattractant protein (MCP)-1 blocked this inflammation-induced monocyte homing to LNs. MCP-1 mRNA in inflamed skin was over 100-fold upregulated and paralleled MCP-1 protein levels, whereas in draining LNs MCP-1 mRNA induction was much weaker and occurred only after a pronounced rise in MCP-1 protein. Thus, MCP-1 in draining LNs was primarily derived from inflamed skin. In MCP-1−/− mice, intracutaneously injected MCP-1 accumulated rapidly in the draining LNs where it enhanced monocyte recruitment. Intravital microscopy showed that skin-derived MCP-1 was transported via the lymph to the luminal surface of HEVs where it triggered integrin-dependent arrest of rolling monocytes. These findings demonstrate that inflamed peripheral tissues project their local chemokine profile to HEVs in draining LNs and thereby exert “remote control” over the composition of leukocyte populations that home to these organs from the blood.
Acupuncture and Counselling for Depression in Primary Care: A Randomised Controlled Trial
Authors: Hugh MacPherson, Stewart Richmond, Martin Bland, Stephen Brealey, Rhian Gabe, Ann Hopton, Ada Keding, Harriet Lansdown, Sara Perren, Mark Sculpher, Eldon Spackman, David Torgerson, Ian Watt
Journal: PLoS Medicine (2013)

Background Depression is a significant cause of morbidity. Many patients have communicated an interest in non-pharmacological therapies to their general practitioners. Systematic reviews of acupuncture and counselling for depression in primary care have identified limited evidence. The aim of this study was to evaluate acupuncture versus usual care and counselling versus usual care for patients who continue to experience depression in primary care. Methods and Findings In a randomised controlled trial, 755 patients with depression (Beck Depression Inventory BDI-II score ≥20) were recruited from 27 primary care practices in the North of England. Patients were randomised to one of three arms using a ratio of 2∶2∶1 to acupuncture (302), counselling (302), and usual care alone (151). The primary outcome was the difference in mean Patient Health Questionnaire (PHQ-9) scores at 3 months with secondary analyses over 12 months follow-up. Analysis was by intention-to-treat. PHQ-9 data were available for 614 patients at 3 months and 572 patients at 12 months. Patients attended a mean of ten sessions for acupuncture and nine sessions for counselling. Compared to usual care, there was a statistically significant reduction in mean PHQ-9 depression scores at 3 months for acupuncture (−2.46, 95% CI −3.72 to −1.21) and counselling (−1.73, 95% CI −3.00 to −0.45), and over 12 months for acupuncture (−1.55, 95% CI −2.41 to −0.70) and counselling (−1.50, 95% CI −2.43 to −0.58). Differences between acupuncture and counselling were not significant. In terms of limitations, the trial was not designed to separate out specific from non-specific effects. No serious treatment-related adverse events were reported. Conclusions In this randomised controlled trial of acupuncture and counselling for patients presenting with depression, after having consulted their general practitioner in primary care, both interventions were associated with significantly reduced depression at 3 months when compared to usual care alone. Trial Registration Controlled-Trials.com ISRCTN63787732 Please see later in the article for the Editors' Summary
Thirty-Six–Item Short-Form Outcomes Following a Randomized Controlled Trial in Type 2 Diabetes
Authors: Felicia Hill-Briggs, Tiffany L. Gary, Kesha Baptiste-Roberts, Frederick L. Brancati
Journal: Diabetes Care (2005)

The goals of clinical interventions in diabetes are to improve not only medical outcomes but health status and health-related quality of life (HRQOL) as well. The Medical Outcomes Study 36-item short form (SF-36) (1) remains the most widely used measure of HRQOL in medical research. We report on change in HRQOL, as assessed using the SF-36, following a randomized controlled trial (RCT) in urban African Americans with type 2 diabetes, a population overrepresented in diabetes prevalence and adverse diabetes outcomes but with relatively little HRQOL research.

Between 1995 and 2000, we conducted a four-arm RCT (2) of the effects of nurse case manager (NCM) and community health worker (CHW) interventions on risk factors for diabetes-related complications in a sample of 186 African Americans with type 2 diabetes in east Baltimore, Maryland. The 2-year trial compared usual care with NCM, CHW, and combined NCM and CHW interventions. The interventions targeted traditional aspects of diabetes care along with socioeconomic factors and home environment. SF-36 was administered at baseline (3) and 2-year follow-up.

One hundred forty-nine persons (84%) completed the 2-year follow-up visit. Pearsons χ2 analyses and two-sample t tests revealed no differences between participants who completed the follow-up and those who did not …