tbuckley/cabot-search huggingface dataset:
Bronchial mucosal dendritic cells in smokers and ex-smokers with COPD: an electron microscopic study
Authors: A V Rogers, E Adelroth, K Hattotuwa, A Dewar, P K Jeffery
Journal: Thorax (2007)

<h3>Background:</h3> Bronchial mucosal dendritic cells (DCs) initiate and regulate immune responses to inhaled antigens, viruses and bacteria. Currently, little is known of their numbers in patients with chronic obstructive pulmonary disease (COPD). While reductions in their numbers have been reported recently in smokers with asthma, nothing is known of the effects of cigarette smoking on bronchial DCs in COPD. The present study compares DC numbers in smokers and ex-smokers with COPD. <h3>Methods:</h3> Endobronchial biopsies were obtained from 15 patients with moderate to severe COPD (10 current smokers with median forced expiratory volume in 1 s (FEV<sub>1</sub>) 45.5% predicted (range 23–68) and 5 ex-smokers with median FEV<sub>1</sub> 30% predicted (range 21–52)), 11 non-smokers with asthma (median FEV<sub>1</sub> 102% predicted (range 89–116)) and 11 non-smoker healthy controls (median FEV<sub>1</sub> 110% predicted (range 92–135)). Transmission electron microscopy (TEM) was used to identify the total population of DCs by their ultrastructure and their number in the epithelium and subepithelium was counted. <h3>Results:</h3> Median (range) DC numbers were significantly lower in current smokers with COPD in the epithelium (0.0 (0.0–156.8) cells/mm<sup>2</sup>) and the subepithelium (4.5 (0.0–63.6) cells/mm<sup>2</sup>) compared with ex-smokers with COPD (97.9 (93.5–170.3) cells/mm<sup>2</sup> in the epithelium (p&lt;0.05); 91.8 (38.2–283.3) cells/mm<sup>2</sup> in the subepithelium (p&lt;0.01)). DC numbers in ex-smokers with COPD were similar to those in subjects with atopic asthma and healthy controls (131.6 (33.3–235.5) cells/mm<sup>2</sup> in the epithelium and 64.4 (0.0–182.4) cells/mm<sup>2</sup> in the subepithelium for the latter). <h3>Conclusions:</h3> In COPD, bronchial mucosal DC numbers are lower in current smokers while, in those who quit, numbers are similar to non-smoking subjects with asthma and non-smoking healthy controls. The functional consequences of the reduction in mucosal DC numbers in smokers with COPD have yet to be determined.
Protein Kinase A–Phosphorylated K <sub>V</sub> 1 Channels in PSD95 Signaling Complex Contribute to the Resting Membrane Potential and Diameter of Cerebral Arteries
Authors: Christopher L. Moore, Piper L. Nelson, Nikhil K. Parelkar, Nancy J. Rusch, Sung W. Rhee
Journal: Circulation Research (2014)

Rationale: Postsynaptic density-95 (PSD95) is a scaffolding protein that associates with voltage-gated, Shaker -type K + (K V 1) channels and promotes the expression of K V 1 channels in vascular smooth muscle cells of the cerebral (cVSMCs) circulation. However, the physiological role of PSD95 in mediating molecular signaling in cVSMCs is unknown. Objective: We explored whether a specific interaction between PSD95 and K V 1 channels enables protein kinase A phosphorylation of K V 1 channels in cVSMCs to promote vasodilation. Methods and Results: Rat cerebral arteries were used for analyses. A membrane-permeable peptide (K V 1-C peptide) corresponding to the postsynaptic density-95, discs large, zonula occludens-1 binding motif in the C terminus of K V 1.2α was designed as a dominant-negative peptide to disrupt the association of K V 1 channels with PSD95. Application of K V 1-C peptide to cannulated, pressurized cerebral arteries rapidly induced vasoconstriction and depolarized cVSMCs. These events corresponded to reduced coimmunoprecipitation of the PSD95 and K V 1 proteins without altering surface expression. Middle cerebral arterioles imaged in situ through cranial window also constricted rapidly in response to local application of K V 1-C peptide. Patch-clamp recordings confirmed that K V 1-C peptide attenuates K V 1 channel blocker (5-(4-phenylalkoxypsoralen))–sensitive current in cVSMCs. Western blots using a phospho-protein kinase A substrate antibody revealed that cerebral arteries exposed to K V 1-C peptide showed markedly less phosphorylation of K V 1.2α subunits. Finally, phosphatase inhibitors blunted both K V 1-C peptide–mediated and protein kinase A inhibitor peptide–mediated vasoconstriction. Conclusions: These findings provide initial evidence that protein kinase A phosphorylation of K V 1 channels is enabled by a dynamic association with PSD95 in cerebral arteries and suggest that a disruption of such association may compromise cerebral vasodilation and blood flow.
Characteristics of exceptional responders to lenalidomide-based therapy in multiple myeloma
Authors: T Vu, W Gonsalves, S Kumar, A Dispenzieri, M Q Lacy, F Buadi, M A Gertz, S V Rajkumar
Journal: Blood Cancer Journal (2015)

Abstract We studied all patients at our institution with a diagnosis of multiple myeloma (MM), from 1 January 2004 to 1 July 2009, who received lenalidomide–dexamethasone (Rd) as initial therapy and had a time to progression of 72 months or longer. Of 240 patients, we identified 33 exceptional responders. Twenty-five patients received primary therapy with Rd and eight patients received Rd induction followed by early stem cell transplantation (SCT). Seven of the eight patients who received SCT did not receive maintenance therapy; one patient received 9 months of lenalidomide post transplant. Fifteen (45%) patients had known clonal plasma cell disorder before the diagnosis of MM. The dominant mode of clinical presentation was with lytic lesions in 28 patients. Of those with informative cytogenetics ( n =24), trisomies were present in 19 (79%), including one patient with concurrent trisomies and t(11;14). Overall, 21 of 24 patients (88%) had either trisomies or t(11;14). None of these exceptional responders had high-risk cytogenetic features at baseline. Twenty-five patients (76%) had a complete response (CR), whereas eight patients (24%) achieved the exceptional response state without ever achieving a CR. We identify a cohort of exceptional responders to Rd-based therapy, representing ~10–15% newly diagnosed MM patients with normal renal function.
North-south divide in social inequalities in Great Britain: Divide in social class inequalities may exist but is small
Authors: J Martin Bland
Journal: BMJ (2004)

EDITOR—Doran et al conclude that a northwest-southeast divide in social class inequalities existed in Great Britain at the start of the 21st century.1 They present tables and summary statistics but no analysis to support this statement. Inspection of their tables shows that the differences between the …
Primed Peripheral Polymorphonuclear Leukocyte
Authors: Shifra Sela, Revital Shurtz-Swirski, Meital Cohen-Mazor, Rafi Mazor, Judith Chezar, Galina Shapiro, Kamal Hassan, Galina Shkolnik, Ronit Geron, Batya Kristal
Journal: Journal of the American Society of Nephrology (2005)

This study characterizes the causal relationship between peripheral polymorphonuclear leukocyte (PMNL) priming, systemic oxidative stress (OS), and inflammation in patients with varying degrees of renal insufficiency (chronic kidney disease [CKD] not on renal replacement therapy [RRT]: continuous ambulatory peritoneal dialysis or hemodialysis [HD]) and healthy control subjects. Rate of superoxide release was measured after stimulation of PMNL with phorbol 12-myristate 13-acetate or zymosan. Priming was estimated by the rate of superoxide release after phorbol 12-myristate 13-acetate stimulation. Systemic OS was related to PMNL priming and intracellular myeloperoxidase activity. Inflammation was linked to peripheral white blood cells and PMNL counts, PMNL apoptosis, and PMNL ex vivo survival in autologous and heterologous sera. PMNL priming and counts were related to the severity of renal failure in CKD not on RRT. Compared with control subjects, PMNL from all CKD patients showed increased priming, highest in HD, with a significant decrease in their response to zymosan. PMNL myeloperoxidase activity and apoptosis were increased in all renal failure patients. Decreased ex vivo cell survival and elevated leukocyte counts were found in all patients, highest in HD. Both PMNL priming and counts correlated negatively with the GFR. A positive significant correlation was shown between PMNL counts and their priming in all groups, suggesting that the increased PMNL count in peripheral blood is an adaptive response to PMNL priming. Hence, PMNL priming is a key mediator of low-grade inflammation and OS associated with renal failure, occurring before the onset of RRT and further augmented in chronic HD.
Transepiploic Hernia: Spontaneous Hernia through the Greater Omentum
Authors: W. H. Davies
Journal: BMJ (1954)

MEDICAL MEMORANDAMEDIALISORNL 689 easy to define.Six months later she was in excellent health.The mass in the lower right abdomen was still present but much smaller, and two normal menstrual periods had occurred.COMMENT The essential anatomy of this case was, in Schumann's (1931).classification, that of an extraperitoneal intraligamen- tary.ectopic pregnancy.An uncommon type, it arises by slow erosion of the Fallopian tube so that the extruded ovum grows out between the layers of the broad ligament.At the time of operation the foetal circulation was still intact, and all tissues, foetal and maternal, were healthy.There was no haemorrhage, thrombosis, sepsis, or adhesions to complicate operation.The placenta, with its maternal blood supply intact, could be safely left and expected to undergo complete absorption.
Noninvasive Measurement of Myocardial Activity Concentrations and Perfusion Defect Sizes in Rats With a New Small-Animal Positron Emission Tomograph
Authors: Takashi Kudo, Kazuki Fukuchi, Alexander J. Annala, Arion F. Chatziioannou, Vivekanand Allada, Magnus Dahlbom, Yuan-Chuan Tai, Masayuki Inubushi, Sung-Cheng Huang, Simon R. Cherry, Michael E. Phelps, Heinrich R. Schelbert
Journal: Circulation (2002)

Background — We explored the feasibility of measuring regional tracer activity concentrations and flow defects in myocardium of rats with a high spatial resolution small-animal PET system (microPET). Methods and Results — Myocardial images were obtained after intravenous 18 F-fluorodeoxyglucose ( 18 FDG) in 11 normal rats (group 1) and assembled into polar maps. Regional 18 F activity concentrations were measured in 9 regions of interest and compared with tissue activity concentrations measured by well counting. In another 9 rats (group 2), myocardial perfusion images were acquired with 13 N -ammonia at baseline and during coronary occlusion. On the polar maps recorded during coronary occlusion, the size of perfusion defects was measured as the myocardium with &lt;50% of maximum activity and expressed as percent total myocardium and was correlated with the area at risk defined by postmortem staining. The diagnostic quality of 18 FDG and 13 N -ammonia microPET images was good to excellent; the images were easily assembled into polar maps. In group 1, regional 18 F concentrations by microPET and postmortem were correlated linearly ( r =0.99; P &lt;0.01 for average and r =0.97; P &lt;0.01 for regional concentrations). In group 2, perfusion defect sizes by microPET and postmortem were correlated linearly ( P &lt;0.01; r =0.93). Conclusions — The findings indicate the feasibility of noninvasive studies of the myocardium in rats with a dedicated small-animal PET-imaging device.
Young adults using e-cigarettes are more likely to progress to smoking, study shows
Authors: Susan Mayor
Journal: BMJ (2015)

Adolescents and young adults who use electronic cigarettes are more likely to progress to smoking tobacco cigarettes than those who do not, shows a small US study that researchers say supports regulations to limit sales and reduce the appeal of e-cigarettes to young people.

The study, published in JAMA Pediatrics ,1 followed up a nationally representative sample of 694 teenagers and young adults aged 16 to 26 who had never smoked. Their attitudes showed that they were not susceptible to smoking cigarettes because they had responded “definitely no” when asked whether they would try a cigarette offered by a friend or whether they believed that they would smoke a cigarette within the next year.

The young people completed a survey about smoking when they were …
You're Only Old Once!
Authors: D. O'Neill
Journal: BMJ (2011)

Dignity is a hard concept to master, especially with care of older people, the key demographic of adult medicine. Clinicians sometimes confound undignified practice and clinical settings with a loss of dignity in the person. Equally, the lay public may describe those with illnesses such as dementia as having “lost their dignity.”

Yet the intrinsic dignity of humans is inviolable, no matter the illness or disability: it is our unthinking attitudes and practice that combine to add indignities to our exchanges with patients. These include failure to provide adequately tailored environments, personalised approaches to care, and a true engagement that compensates for asymmetry of …
Posttraumatic Stress Disorder Comorbid With Major Depression: Factors Mediating the Association With Suicidal Behavior
Authors: Maria Oquendo, David A Brent, Boris Birmaher, Laurence Greenhill, David Kolko, Barbara Stanley, Jamie Zelazny, Ainsley K Burke, Sekip Firinciogullari, Steven P Ellis, J John Mann
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The purpose of the study was to determine if patients with a history of major depressive episode and comorbid posttraumatic stress disorder (PTSD) have a higher risk for suicide attempt and differ in other measures of suicidal behavior, compared to patients with major depressive episode but no PTSD. In addition, to explore how PTSD comorbidity might increase risk for suicidal behavior in major depressive episode, the authors investigated the relationship between PTSD, cluster B personality disorder, childhood sexual or physical abuse, and aggression/impulsivity. METHOD: The subjects were 230 patients with a lifetime history of major depressive episode; 59 also had lifetime comorbid PTSD. The demographic and clinical characteristics of subjects with and without PTSD were compared. Multivariate analysis was used to examine the relationship between suicidal behavior and lifetime history of PTSD, with adjustment for clinical factors known to be associated with suicidal behavior. RESULTS: Patients with a lifetime history of PTSD were significantly more likely to have made a suicide attempt. The groups did not differ with respect to suicidal ideation or intent, number of attempts made, or maximum lethality of attempts. The PTSD group had higher objective depression, impulsivity, and hostility scores; had a higher rate of comorbid cluster B personality disorder; and were more likely to report a childhood history of abuse. However, cluster B personality disorder was the only independent variable related to lifetime suicide attempts in a multiple regression model. CONCLUSIONS: PTSD is frequently comorbid with major depressive episode, and their co-occurrence enhances the risk for suicidal behavior. A higher rate of comorbid cluster B personality disorder appears to be a salient factor contributing to greater risk for suicidal acts in patients with a history of major depressive episode who also have PTSD, compared to those with major depressive episode alone.
Nocturnal asthma: slow-release terbutaline versus slow-release theophylline therapy
Authors: M Heins, L Kurtin, M Oellerich, R Maes, GW Sybrecht
Journal: European Respiratory Journal (1988)

In a double-blind cross-over study, the effects of slow release (S-R) terbutaline tablets (b.i.d. 0.25 mg/kg per day) and S-R theophylline (5.31 mg/kg morning and 10.62 mg/kg evening) were compared in eleven patients with nocturnal asthma. On day seven of each treatment period, drug serum concentrations and peak expiratory flow (PEF) were measured every 2h over a 24-h period. During daytime, terbutaline concentrations ranged from 1.6-14.1 (median 4.5) microgram/l and during the night from 2.1-18.7 (median 4.9) micron/l. Theophylline concentrations ranged from 3.9-24.3 (median 11.5) mg/l during the day and from 3.3-20.9 (median 10.4) mg/l at night. Nocturnal wheezing occurred during theophylline treatment in four patients 7 times and during terbutaline treatment in six patients 22 times. Daytime PEF values were 472 +/- 161 l/min during theophylline therapy versus 445 +/- 169 l/min during terbutaline therapy (p less than 0.05). In the night and early morning there was no significant difference between PEF values with the two treatment forms. During theophylline treatment, fewer inhalations of beta 2-sympathomimetics were used, and there were fewer side effects. One patient experienced severe asthmatic attacks during the terbutaline treatment period. The patients preferred theophylline for the treatment of nocturnal asthma.
Proteomic Analysis of Lung Tissues From Patients With Pulmonary Arterial Hypertension
Authors: Vahitha B. Abdul-Salam, John Wharton, John Cupitt, Mark Berryman, Robert J. Edwards, Martin R. Wilkins
Journal: Circulation (2010)

Pulmonary arterial hypertension is a disorder of vascular remodeling causing increased resistance to pulmonary blood flow. The expression of proteins in lungs from pulmonary arterial hypertension patients was investigated in an unbiased approach to further understand the pathobiology of this disease.Label-free liquid chromatography tandem mass spectrometry was used to compare protein profiles in surgical samples of lungs from 8 patients with pulmonary arterial hypertension and 8 control subjects. More than 300 proteins were detected. On the basis of robust criteria, the levels of 25 proteins varied between the 2 groups. The majority of upregulated proteins were associated with cell growth, proliferation, and cell metabolism. Novel findings included an increased expression of chloride intracellular channel 4, receptor for advanced glycation end products, and periostin. Increased expression of chloride intracellular channel 4, a multifunctional protein involved in angiogenesis, and several signaling pathways implicated in pulmonary arterial hypertension--transforming growth factor-β, vascular endothelial growth factor, and bone morphogenetic protein--was confirmed by Western blotting and localized predominantly to endothelial cells in occlusive and plexiform vascular lesions.Label-free proteomics identified differences in the expression of several proteins in the pulmonary arterial hypertension lung, many of which are relevant to the disease process. Increased expression of chloride intracellular channel 4 may be pertinent to the disorganized angiogenesis of plexiform lesions.
Outcomes and Toxicity in African-American and Caucasian Patients in a Randomized Adjuvant Chemotherapy Trial for Colon Cancer
Authors: A. D. McCollum
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Previous studies have demonstrated that African-Americans with colon cancer have worse overall and stage-specific survival rates than Caucasians. Such differences could reflect variation in access to health care, in tumor biology, or in treatment efficacy. Little is known about potential differences in chemotherapy-related toxicities between African-Americans and Caucasians. In this study, we examined survival and toxic effects among African-American and Caucasian patients enrolled in a large, randomized phase III trial of adjuvant chemotherapy for resected colon cancer. Methods: We analyzed data on 3380 patients (344 African-Americans and 3036 Caucasians) enrolled in a randomized trial of adjuvant 5-fluorouracil-based chemotherapy in patients with stage II (high risk) and stage III colon cancer to evaluate differences in outcomes and toxicity. We compared disease-free survival (DFS) and overall survival (OS) between African-Americans and Caucasians by the Kaplan–Meier method, computed Cox proportional hazards by multivariable analysis, and compared treatment-related toxicity rates by Fisher's exact test. All statistical tests were two-sided. Results: We found no differences in DFS or OS between African-American and Caucasian patients. Five-year DFS was 57% (95% confidence interval [CI] = 52% to 62%) for African-Americans and 58% (95% CI = 56% to 60%) for Caucasians (P = .15), and 5-year OS was 65% (95% CI = 60% to 70%) for African-Americans and 66% (95% CI = 64% to 68%) for Caucasians (P = .38). On multivariable analysis, no statistically significant difference in disease recurrence or death was detected between the racial/ethnic groups (hazard ratios for African-Americans versus Caucasians: disease recurrence = 1.1, 95% CI = 0.9 to 1.3; death = 1.1, 95% CI = 0.9 to 1.3). Treatment-related toxicity differed between the African-American and Caucasian patients, with African-Americans experiencing statistically significantly lower rates of diarrhea (P<.001), nausea (P<.001), vomiting (P = .01), stomatitis (P<.001), and overall toxicity (P = .005). Conclusions: In this study of patients with similar access to health care resources and treatment with adjuvant chemotherapy, we found similar 5-year DFS and OS in African-Americans and Caucasians with stage II and III colon cancer. The two groups derived similar benefits from adjuvant chemotherapy. Moreover, African-Americans appeared to experience less treatment-related toxicity.
MEPACRINE DRUG ERUPTION AFFECTING A TOOTH
Authors: G. A. GRANT PETERKIN
Journal: British Journal of Dermatology (1949)

Journal Article MEPACRINE DRUG ERUPTION AFFECTING A TOOTH Get access G. A. GRANT PETERKIN G. A. GRANT PETERKIN Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 61, Issue 8-9, 1 August 1949, Pages 287–288, https://doi.org/10.1111/j.1365-2133.1949.tb11102.x Published: 01 August 1949
Bisphosphonates and Fractures of the Subtrochanteric or Diaphyseal Femur
Authors: Dennis M. Black, Michael P. Kelly, Harry K. Genant, Lisa Palermo, Richard Eastell, Christina Bucci-Rechtweg, Jane Cauley, Ping Chung Leung, Steven Boonen, Arthur Santora, Anne de Papp, Douglas C. Bauer
Journal: New England Journal of Medicine (2010)

A number of recent case reports and series have identified a subgroup of atypical fractures of the femoral shaft associated with bisphosphonate use. A population-based study did not support this association. Such a relationship has not been examined in randomized trials.
Linkage of β1-adrenergic stimulation to apoptotic heart cell death through protein kinase A–independent activation of Ca2+/calmodulin kinase II
Authors: Wei-Zhong Zhu, Shi-Qiang Wang, Khalid Chakir, Dongmei Yang, Tong Zhang, Joan Heller Brown, Eric Devic, Brian K. Kobilka, Heping Cheng, Rui-Ping Xiao
Journal: Journal of Clinical Investigation (2003)

beta(1)-adrenergic receptor (beta(1)AR) stimulation activates the classic cAMP/protein kinase A (PKA) pathway to regulate vital cellular processes from the change of gene expression to the control of metabolism, muscle contraction, and cell apoptosis. Here we show that sustained beta(1)AR stimulation promotes cardiac myocyte apoptosis by activation of Ca(2+)/calmodulin kinase II (CaMKII), independently of PKA signaling. beta(1)AR-induced apoptosis is resistant to inhibition of PKA by a specific peptide inhibitor, PKI14-22, or an inactive cAMP analogue, Rp-8-CPT-cAMPS. In contrast, the beta(1)AR proapoptotic effect is associated with non-PKA-dependent increases in intracellular Ca(2+) and CaMKII activity. Blocking the L-type Ca(2+) channel, buffering intracellular Ca(2+), or inhibiting CaMKII activity fully protects cardiac myocytes against beta(1)AR-induced apoptosis, and overexpressing a cardiac CaMKII isoform, CaMKII-deltaC, markedly exaggerates the beta(1)AR apoptotic effect. These findings indicate that CaMKII constitutes a novel PKA-independent linkage of beta(1)AR stimulation to cardiomyocyte apoptosis that has been implicated in the overall process of chronic heart failure.