tbuckley/cabot-search huggingface dataset:
β-Adrenergic Regulation of the L-type Ca <sup>2+</sup> Channel Does Not Require Phosphorylation of α <sub>1C</sub> Ser <sup>1700</sup>
Authors: Lin Yang, Alexander Katchman, Tahmina Samad, John P. Morrow, Richard L. Weinberg, Steven O. Marx
Journal: Circulation Research (2013)

Rationale: Sympathetic nervous system triggered activation of protein kinase A, which phosphorylates several targets within cardiomyocytes, augments inotropy, chronotropy, and lusitropy. An important target of β-adrenergic stimulation is the sarcolemmal L-type Ca 2+ channel, Ca V 1.2, which plays a key role in cardiac excitation–contraction coupling. The molecular mechanisms of β-adrenergic regulation of Ca V 1.2 in cardiomyocytes, however, are incompletely known. Recently, it has been postulated that proteolytic cleavage at Ala 1800 and protein kinase A phosphorylation of Ser 1700 are required for β-adrenergic modulation of Ca V 1.2. Objective: To assess the role of Ala 1800 in the cleavage of α 1C and the role of Ser 1700 and Thr 1704 in mediating the adrenergic regulation of Ca V 1.2 in the heart. Methods and Results: Using a transgenic approach that enables selective and inducible expression in mice of FLAG-epitope–tagged, dihydropyridine-resistant Ca V 1.2 channels harboring mutations at key regulatory sites, we show that adrenergic regulation of Ca V 1.2 current and fractional shortening of cardiomyocytes do not require phosphorylation of either Ser 1700 or Thr 1704 of the α 1C subunit. The presence of Ala 1800 and the 1798 NNAN 1801 motif in α 1C is not required for proteolytic cleavage of the α 1C C-terminus, and deletion of these residues did not perturb adrenergic modulation of Ca V 1.2 current. Conclusions: These results show that protein kinase A phosphorylation of α 1C Ser 1700 does not have a major role in the sympathetic stimulation of Ca 2+ current and contraction in the adult murine heart. Moreover, this new transgenic approach enables functional and reproducible screening of α 1C mutants in freshly isolated adult cardiomyocytes in a reliable, timely, cost-effective manner.
Addiction to Meprobamate
Authors: John A. Ewing, R. E. Fullilove
Journal: New England Journal of Medicine (1957)

THE use of meprobamate§ has become widespread in a variety of disturbances of emotional origin. Physicians are under much demand for this drug from patients whose information is obtained largely from the lay press, radio and television. Hence, they are now faced with the situation in which huge quantities are consumed and yet the possible adverse effects are only beginning to be recognized.The search for such an agent was stimulated by reports of beneficial emotional effects from the muscle-relaxing drug mephenesin1 , 2 , 3 although controlled trials were not so promising.4 , 5 Berger's6 report of the pharmacologic properties of meprobamate led to its . . .
Continuity of Care and the Risk of Preventable Hospitalization in Older Adults
Authors: David J. Nyweide, Denise L. Anthony, Julie P. W. Bynum, Robert L. Strawderman, William B. Weeks, Lawrence. P. Casalino, Elliott S. Fisher
Journal: JAMA Internal Medicine (2013)

<h3>Importance</h3> Preventable hospitalizations are common among older adults for reasons that are not well understood. <h3>Objective</h3> To determine whether Medicare patients with ambulatory visit patterns indicating higher continuity of care have a lower risk of preventable hospitalization. <h3>Design</h3> Retrospective cohort study. <h3>Setting</h3> Ambulatory visits and hospital admissions. <h3>Participants</h3> Continuously enrolled fee-for-service Medicare beneficiaries older than 65 years with at least 4 ambulatory visits in 2008. <h3>Exposures</h3> The concentration of patient visits with physicians measured for up to 24 months using the continuity of care score and usual provider continuity score on a scale from 0 to 1. <h3>Main Outcomes and Measures</h3> Index occurrence of any 1 of 13 preventable hospital admissions, censoring patients at the end of their 24-month follow-up period if no preventable hospital admissions occurred, or if they died. <h3>Results</h3> Of the 3 276 635 eligible patients, 12.6% had a preventable hospitalization during their 2-year observation period, most commonly for congestive heart failure (25%), bacterial pneumonia (22.7%), urinary infection (14.9%), or chronic obstructive pulmonary disease (12.5%). After adjustment for patient baseline characteristics and market-level factors, a 0.1 increase in continuity of care according to either continuity metric was associated with about a 2% lower rate of preventable hospitalization (continuity of care score hazard ratio [HR], 0.98 [95% CI, 0.98-0.99; usual provider continuity score HR, 0.98 [95% CI, 0.98-0.98). Continuity of care was not related to mortality rates. <h3>Conclusions and Relevance</h3> Among fee-for-service Medicare beneficiaries older than 65 years, higher continuity of ambulatory care is associated with a lower rate of preventable hospitalization.
Abstract 1168: Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis .
Authors: Dong-Hyung Cho, Yoon Kyung Jo, Seung Cheol Kim, In Ja Park, Jin Cheon Kim
Journal: Cancer Research (2013)

Abstract Autophagy has paradoxical and complex functions in cancer development, and autophagy-related genes (ATG) are key regulators in autophagy. Until now, more than 30 different ATG proteins have been identified in yeast, and their mammalian counterparts also have been reported. Although the roles of a few ATG proteins in cancer have been characterized, the role of ATG10 is almost completely unknown. To investigate the clinicopathological role of ATG10 in colorectal cancer, we analyzed ATG10 expression in colorectal cancer tissues and cell lines. Protein expression analysis showed that ATG10 is highly increased in colorectal cancer (tissue - 18/37 cases, 48%; cell line - 8/12 cell lines, 66%). Immunohistochemical analysis with clinicopathological features indicated a strong association of the up-regulation of ATG10 with tumor lymph node metastasis (p=0.005) and invasion (p&amp;lt;0.001). Moreover, both 5-year disease free survival and overall survival rates of patients bearing tumors that did not express ATG10 were significantly higher than those of patients bearing ATG10-expressing tumors (p=0.012). Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis indicating that ATG10 may be a potential prognostic maker in colorectal cancer. Citation Format: Dong-Hyung Cho, Yoon Kyung Jo, Seung Cheol Kim, In Ja Park, Jin Cheon Kim. Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1168. doi:10.1158/1538-7445.AM2013-1168
Reduction of experimental myocardial infarct size by infusion of lactosylphenyl Trolox
Authors: T.-W. Wu, J. Wu, L. H Zeng, H. Sugiyama, D. A Mickle, J. X Au
Journal: Cardiovascular Research (1993)

The aim was to determine if lactosylphenyl Trolox could improve myocardial resistance to ischaemia and reperfusion. Lactosylphenyl Trolox is derived by coupling p-aminophenyl-beta-D-lactopyranoside to Trolox. Trolox, a polar analogue of vitamin E, has been found to protect human cardiomyocytes against oxyradicals and to reduce myocardial damage by 66% in a canine ischaemia-reperfusion model.New Zealand white rabbits (weighing approximately 3.5 kg) were subjected to 1 h ischaemia by ligation of the main branch of the anterior ventricular coronary artery. Approximately 1-2 min before release of ischaemia, a 30 ml bolus of saline (placebo control) or saline containing lactosylphenyl Trolox was injected into the right external jugular vein, followed by 3 h reperfusion. The area at risk was identified by staining with Evans Blue. Area of necrosis was indicated by tetrazolium red staining, confirmed by histopathology and quantified by planimetry.The control group (n = 6) had 46.6(SD 10.0)% necrosis of the area at risk but the lactosylphenyl Trolox treated groups (n = 6 per group) had reduced necrosis: 34.0(6.5)%, 17.4(8.2)%, and 6.9(3.6)% at doses of 2.5, 5.0, and 10 mumol.kg-1, respectively (each with p < 0.05 v control value). These translated to 48.6(14.0)%, 62.7(17.6)%, and 85.3(7.8)% myocardial salvage, respectively. In contrast, the salvages achieved with 2.5 and 10 mumol.kg-1 of Trolox were 31.0(11.0)% and 62.1(18.9)% respectively (both p < 0.05 v lactosylphenyl Trolox).Lactosylphenyl Trolox reduces myocardial infarct size more effectively than Trolox in a rabbit model of ischaemia-reperfusion.
Reduction by Paroxetine of Suicidal Behavior in Patients With Repeated Suicide Attempts But Not Major Depression
Authors: Robbert J. Verkes, Rose C. Van der Mast, Michiel W. Hengeveld, Jolien P. Tuyl, Aeilko H. Zwinderman, Godfried M.J. Van Kempen
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: Suicidal behavior has been associated with reduced central serotonergic function. Because selective serotonin reuptake inhibitors (SSRIs) enhance serotonergic function, the authors studied the efficacy of an SSRI, paroxetine, in the prevention of recurrent suicidal behavior. METHOD: They conducted a 1-year double-blind study comparing paroxetine (40 mg/day) and placebo in 91 patients who had recently attempted suicide for at least a second time. None of the patients had experienced a major depressive episode or had any other major DSM-III-R axis I diagnoses. At least one cluster B personality disorder was present in 74 patients. RESULTS: With adjustment for the number of previous suicide attempts, paroxetine showed significant efficacy in the prevention of recurrent suicidal behavior. Among the patients who had attempted suicide fewer than five times, 12 (36%) in the placebo group (N=33) and five (17%) in the paroxetine group (N=30) made a subsequent suicide attempt. Paroxetine was also significantly more effective in patients who met fewer than 15 criteria for cluster B personality disorders than in those who met more than 15 criteria. Overall, paroxetine was not significantly different from placebo in its effect on depressive mood, hopelessness, and anger. However, the data suggest that paroxetine may have some temporary effect in reducing anger. CONCLUSIONS: This study indicates that enhancing serotonergic function with an SSRI may reduce suicidal behavior in a subgroup of patients who have attempted suicide more than once but who do not suffer from major depression.
288 Hepatic venous pressure gradient (HVPG) predicts early recurrence of varices and rebleeding after endoscopic band ligation (EBL)
Authors: S ALONSO, R BANARES, A ALBILLOS, J CALLEJA, D RINCON, M GONZALEZ, C GONZALEZASANZA, E VAZQUEZSIQUEIROS, L RUIZDELARBOL, P MENCHEN
Journal: Hepatology (2003)
Thrombocytopenia with Sodium Cephalothin Therapy
Authors: HARVEY R. GRALNICK
Journal: Annals of Internal Medicine (1972)

Thrombocytopenia occurred on two separate occasions in a patient while she was receiving sodium cephalothin. After recovery, a test dose of cephalothin (1 g) produced a 50% drop in the platelet count. A month later a survival study of 51Cr-labeled autologous platelets was normal. During the survival study a 1-g infusion of cephalothin produced a rapid disappearance of platelets and accelerated loss of radioactivity. In vitro studies showed a specific anticephalothin antibody in the patient's serum. When cephalothin was added in vitro to the patient's platelets, her serum agglutinated these coated platelets but not her own uncoated platelets. This activity could be neutralized by prior incubation of the serum with cephalothin. A second patient with cephalothin-induced thrombocytopenia had similar in vivo results with unlabeled platelets. These studies suggested the production of a specific antibody that binds to cephalothin-coated platelets and results in a shortened platelet survival and thrombocytopenia.
Epidermal cyst containing numerous spherules of keratin
Authors: H. Hattori
Journal: British Journal of Dermatology (2004)

Sir, Epidermal cyst is classified by the World Health Organization as a tumour associated with hair follicles.1 It is closely related to infundibular cyst, which is defined as a cystic nodule of the dermis lined by stratified squamous epithelium with a granular layer containing laminated keratin.1 We have encountered a peculiar variant of epidermal cyst. A 56‐year‐old man had two subcutaneous nodules on the back, each measuring 10 × 10 mm. They were excised because of a tendency to enlarge. One of the nodules was an ordinary epidermal cyst, whereas the other showed peculiar features. It was soft to the touch and, macroscopically, a cut section showed a cyst with smooth contours. The contents of the cyst were brownish in colour and lumpy in texture, somewhat resembling bone marrow (Fig. 1). Microscopically, the cyst was lined by an epidermis with granular cells and orthokeratinization. The contents of the cyst consisted of numerous closely packed and loosely joined spherules with even dimensions, composed of keratin (Fig. 2a). Spherule formation began from just above the keratinous layer of the lining epithelium (Fig. 2b). Shadow cell‐like foci with mild mineralization were observed very focally (Fig. 2c).
The Psychosocial Aspects of Advanced Cancer
Authors: Edmund C. Payne
Journal: JAMA (1969)

Failure to obtain psychological and social information regarding a patient with a lethal long-term illness and his family may lead to inappropriate medical decision-making and treatment, and thus result in failure to meet the patient's major needs. The use of simple interviewing techniques by nonpsychiatrist physicians and medical students can yield important information concerned with patient care. This information should become part of the medical record in order to document the data as any other pertinent historical or physical data, to transmit this information to other physicians who may review the medical record, and to serve as a self-imposed discipline as the physician learns to expand his communication with the patient.
PHF11 is Not a Major Candidate Gene for Eczema or Asthma in Chinese Children
Authors: T.F. Leung, H.Y. Sy, I.H.S. Chan, G.W.K. Wong, C.Y. Li, M.M.Y. Waye, C.W.K. Lam, K.L.E. Hon
Journal: Journal of Allergy and Clinical Immunology (2010)
Jamie's School Dinners
Authors: Des Spence
Journal: BMJ (2005)

Channel 4, 23 February to 16 March at 9 pm Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> T his series was more terrifying than The Exorcist . Jamie Oliver—loudmouth, Essex boy, school failure, and now celebrity chef—sets out to bring healthy school dinners to a whole London borough. His four part info-doc could have been dismissed as a self serving publicity stunt, but nothing prepared viewers for the real life horror they were to endure—lines of children shuffling along waiting for burgers, chicken nuggets, pizza, and chips, all washed down with carbonated syrup. We are told it's “what they want” and “it's all that they will eat.” Jamie, however, has a different … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
The Veterans Administration Clinical Investigator Program
Authors: Edward Dunner
Journal: JAMA (1970)

Twelve years' experience with the Veterans Administration (VA) Clinical Investigator (CI) Program was evaluated. A 100% follow-up of 206 former Cls indicates that the original goals have been realized, in that 40% of these investigators are on VA hospital rosters, 35% more are on medical school staffs, and the Cls entering civilian practice undoubtedly improve the quality of medical care wherever located. Further, there is evident a heavy commitment to patient care, teaching, and research. Efforts to augment numbers of physicians in specialties where shortages persisted resulted in the introduction of additional steps in the program, leading eventually to a five-step career ladder research and education program.
349. Pretreatment of the Esophagus with Manganese Superoxide Dismutase-Plasmid Liposome (MnSOD-PL) Complex Increases Migration and Proliferation of Marrow Stem Cell Progenitors of Esophageal Squamous Epithelium
Authors: Yunyun Niu, Michael W. Epperly, Joel S. Greenberger
Journal: Molecular Therapy (2006)

Following irradiation of the murine esophagus there is detectable migration of marrow origin stem cells into the esophagus associated with recovery from irradiation-induced damage. Irradiation of the esophagus or the bone marrow results in stably increased detectable production of reactive oxygen species (ROS) for weeks. We hypothesized that reducing the production of ROS following irradiation may allow for increased stable recruitment of stem cells into the irradiated areas. C57BL/6NHsd female mice were administered MnSOD-PL (100 |[mu]|g plasmid DNA) by intraesophageal injection 24 hours before irradiation to 29 Gy. Control mice were irradiated to 29 Gy. The mice were then injected I.V. with bone marrow cells isolated from ROSA (LacZ+) male mice. Fourteen days after irradiation mice were sacrificed and the esophagus excised and sorted into side population (SP) and non-SP cells. In mice that received MnSOD-PL prior to irradiation, 40% of the non-SP cells were LacZ+ compared to 10% in mice that received irradiation only. Sorting of esophageal SP cells which include multilineage stem cells showed 20% from MnSOD-PL pretreated then irradiated mice were LacZ+ compared to 8% of the SP cells from control irradiated mice. In addition, mice that received MnSOD-PL intraesophageally 24 hours before irradiation also had decreased apoptotic cells. At day 5 following irradiation, 20% of control irradiated esophageal cells were undergoing apoptosis; whereas, in mice that were pre-treated with MnSOD-PL there was less than 1% apoptosis. In conclusion, administration of MnSOD-PL results in increased migration of stem cells from the bone marrow into the esophagus and decreased apoptosis in the esophagus. The data suggest that MnSOD-PL pre- irradiation treatment of the esophagus results in increased marrow cell engraftment due to reduction of ROS.
Immediate-type hypersensitivity reactions to proton pump inhibitors: usefulness of skin tests in the diagnosis and assessment of cross-reactivity
Authors: S. Kepil Özdemir, İ. Yılmaz, Ö. Aydın, S. Büyüköztürk, A. Gelincik, M. Demirtürk, D. Erdoğdu, Ş. Cömert, T. Erdoğan, G. Karakaya, A. F. Kalyoncu, F. Öner Erkekol, A. B. Dursun, Z. Mısırlıgil, S. Bavbek
Journal: Allergy (2013)

Background Data are limited about the value of skin tests in the diagnosis of proton pump inhibitor (PPI)-induced hypersensitivity reactions and the cross-reactivity between PPIs. We aimed to assess the role of skin testing in the diagnosis of PPI-related immediate hypersensitivity reactions and the cross-reactivity patterns among PPIs. Methods The study was designed in a prospective, national, multicentre nature. Sixty-five patients with a suggestive history of a PPI-induced immediate hypersensitivity reaction and 30 control subjects were included. Standardized skin prick and intradermal tests were carried out with a panel of PPIs. Single-blind, placebo-controlled oral provocation tests (OPTs) with the PPIs other than the culprit PPI that displayed negative results in skin tests (n = 61) and diagnostic OPTs with the suspected PPI (n = 12) were performed. Results The suspected PPIs were lansoprazole (n = 52), esomeprazole (n = 11), pantoprazole (n = 9), rabeprazole (n = 2), and omeprazole (n = 1). The sensitivity, specificity, and negative and positive predictive values of the skin tests with PPIs were 58.8%, 100%, 70.8%, and 100%, respectively. Fifteen of the 31 patients with a hypersensitivity reaction to lansoprazole had a positive OPT or skin test result with at least one of the alternative PPIs (8/52 pantoprazole, 6/52 omeprazole, 5/52 esomeprazole, 3/52 rabeprazole). Conclusion Considering the high specificity, skin testing seems to be a useful method for the diagnosis of immediate-type hypersensitivity reactions to PPIs and for the evaluation of cross-reactivity among PPIs. However, OPT should be performed in case of negativity on skin tests.
Diethylcarbamazine in Tropical Pulmonary Eosinophilia
Authors: A. Shanker, R. K. Bhargava, B. N. Shrivastava
Journal: BMJ (1960)

PERNICIOUS ANAEMIABDICALJou& average being 59.Every patient was requested to attend for supervision at intervals of four weeks.Injections of 1,000 jug. of vitamin B12 (" cytamen ") were given once every 12 weeks.The haemoglobin and red-cell count were estimated at least every 12 weeks, and more often if the levels were not entirely satisfactory.Serum vitamin B12 assays were performed on the majority of patients, using the method described by Ross (1952) modified by Hutner et al. (1956) using Euglena gracilis 3 strain as the test organism.Samples were obtained at 18 months at random intervals of one, two, or three months after vitamin-B12 administration. ResultsTo determine whether or not there was any deterioratio-n in the haematological values during the course of the trial the mean of the first three and the mean of the last three red-cell counts and haemoglobin estimations were compared.The haematological levels at which it was considered desirable to maintain patients were: -for men: haemoglobin 100%, red-cell count 5,000,000/c.mm.; for women: haemoglobin 90%, red- cell count 4,500,000/c.mm.During the course of the trial three patients died from other diseases and nine were withdrawn owing to intercurrent illness or inability to attend.Of the remaining 100, 87 were maintained in the trial throughout a two-year period of study and showed no deterioration in their red-cell counts or haemoglobin values.Seventeen of these, however, were maintained with red-cell counts slightly under the desired levels, and two required intermittent oral iron therapy to maintain their haemoglobin levels.Thirteen patients were withdrawn from the trial at intervals varying from 9 to 16 months (mean 14 months) on account of unsatisfactory red-cell counts, though none were below 4,000,000/c.mm., and in these cases the dosage of vitamin B, was increased to 1,000 ug.monthly in an effort to determine whether or not an improvement might be obtained.Of this group, one patient had, after 12 months in the trial, developed paraesthesia of the hands and feet, which did not clear up until the dosage of vitamin B12 had been increased to fortnightly.Three patients were known to have other disease: one had mild rheumatoid arthritis, one had been under out-patient treatment for a year for pulmonary tuberculosis, and one had a probable bronchial carcinoma.These four patients had the lowest haematological values in the whole survey.Eleven of these 13 cases showed a rise of the red-cell count of 100,000-400,000/c.mm. (mean 300,000/c.mm.) following the more intensive vitamin-B12 therapy.These must be accepted as failures of the regime.Serum vitamin-B,2 assays performed on the first group