tbuckley/cabot-search huggingface dataset:
Noninvasive Quantification of the Contractile Reserve of Stunned Myocardium by Ultrasonic Strain Rate and Strain
Authors: Fadi Jamal, Jörg Strotmann, Frank Weidemann, Tomasz Kukulski, Jan D’hooge, Bart Bijnens, Frans Van de Werf, Ivan De Scheerder, George R. Sutherland
Journal: Circulation (2001)

Background We sought to investigate ultrasonic strain rate and strain as new indices to quantify the contractile reserve of stunned myocardium during dobutamine infusion. Methods and Results Stunning of the left ventricular posterior wall was induced in 9 closed-chest pigs after 30 minutes of severe hypoperfusion followed by 60 minutes of reperfusion of the left circumflex coronary artery territory. A second group of 7 animals had no coronary occlusion and served as normal controls. An incremental dobutamine infusion protocol was used in both groups. Changes in regional radial function were monitored by use of ultrasound-derived maximal systolic radial strain rate (SR) and systolic strain (ε). In the control group, dobutamine induced an increase in both SR and maximal dP/dt, which correlated linearly ( r =0.85). Conversely, ε values increased at low doses of dobutamine (2.5 to 5 μg · kg −1 · min −1 ) but decreased during higher infusion rates (10 to 20 μg · kg −1 · min −1 ). During circumflex hypoperfusion, SR and ε of the posterior wall decreased from 5.0±0.3 s −1 and 63±6% to 2.9±0.3 s −1 and 27±4%, respectively ( P &lt;0.01). After 60 minutes of reperfusion, SR and ε failed to fully resume because of stunning, averaging 3.6±0.2 s −1 and 35±3%, respectively ( P =0.12 versus ischemia, P &lt;0.05 versus baseline). During dobutamine infusion, SR increased at 5 μg · kg −1 · min −1 and exceeded baseline values at 20 μg · kg −1 · min −1 ( P &lt;0.05), whereas ε increased only at high doses and remained below baseline levels ( P &lt;0.05). Conclusions The changes in regional function of stunned myocardium during inotropic stimulation could be characterized by use of ultrasonic deformation parameters. During dobutamine infusion, strain-rate values quantified the contractile reserve better than strain values.
PLEKHA5: A Key to Unlock the Blood–Brain Barrier?
Authors: Sylvia C. Eisele, Corey M. Gill, Ganesh M. Shankar, Priscilla K. Brastianos
Journal: Clinical Cancer Research (2015)

Brain metastases represent a devastating complication of melanoma. Our understanding of the mechanisms driving metastasis to the brain is limited. PLEKHA5 functions as a regulator of brain metastasis in melanoma, and further investigation is warranted to explore the use of PLEKHA5 as a potential therapeutic target.
Abstract 2882: Therapeutic effects of ormeloxifene on cervical cancer
Authors: Neeraj Chauhan, Diane M. Maher, Murali M. Yallapu, Mara C. Ebeling, Meena Jaggi, Subhash C. Chauhan
Journal: Cancer Research (2012)

Abstract Background: Cervical cancer is one of the most common and deadly cancers among women worldwide and is strongly associated with persistent Human Papillomavirus (HPV) infection. HPV E6/E7 oncoproteins are well known to interfere with p53 and retinoblastoma (Rb) proteins and drive the development of cervical cancer. While screening for cervical cancer can reduce the incidence and mortality, treatment of advanced stage cervical cancer is difficult and often unsuccessful. Therefore, there is an urgent need for the development of additional treatment modalities. Ormeloxifene is a non-hormonal anti-estrogen oral contraceptive for human use and it effectively suppresses the highly proliferative decidual cells in the endometrium to inhibit egg implantation. Considering its strong anti-proliferative effect, we hypothesized that ormeloxifene may inhibit the growth of cervical cancer cells and may suppress the expression of HPV oncoproteins E6/E7. Methods: The effect of ormeloxifene on the proliferation of various cervical cancer cell lines (Caski, SiHa, C33A, and HT3) was determined by MTS and colony formation assay. Annexin V/7AAD and propidium iodide (PI) staining was analyzed by flow cytometry to determine ormeloxifene's effect on apoptosis and cell cycle inhibition, respectively. The expression of apoptotic proteins such as poly (ADP-ribose) polymerase (PARP), Caspase 3 and Caspase 9 was determined by immunoblotting. The potential of ormeloxifene to repress the expression of HPV E6/E7 oncogenes was determined by quantitative RT-PCR and immunoblotting analyses. Further, the efficacy of ormeloxifene to restore tumor suppressor proteins, such as p53 and Rb, was also determined by immunoblotting. Results: In all 4 cell lines, ormeloxifene effectively inhibited cervical cancer cell growth. Ormeloxifene treatment induced apoptosis in cervical cancer cells as determined by staining for Annexin V/7AAD and immunoblotting for cleaved PARP, Caspase 3, and Caspase 9. PI staining also clearly revealed that ormeloxifene treatment arrests Caski cells in the G0-G1 phase. Additionally, ormeloxifene treatment caused a marked decrease in the levels of HPV E6 and E7 oncogenes and restored the levels of p53 and Rb proteins in Caski cells. Conclusion: Our findings show that ormeloxifene significantly inhibits cervical cancer cell growth and down-regulates HPV E6/E7 oncogenes, therefore; ormeloxifene may be novel chemo-preventive and treatment method for the management of cervical cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2882. doi:1538-7445.AM2012-2882
Problems Facing the Negro in Medicine Today
Authors: M. Alfred Haynes
Journal: JAMA (1969)

I have been asked to touch briefly on the whole area which we will cover today: the problems facing the Negro today, first as a medical student, then in postgraduate training, and finally in actual practice. <h3>The Medical Student</h3> Much progress has been made, especially in recent years, but many problems still face the Negro in medicine today. A few years ago, the black applicant to medical school was fairly limited in his choice. He applied to Howard University and to Meharry Medical College. If he applied elsewhere, it was really an act of courage because he knew that his chances were fairly slim. Today the average black student still makes a smaller number of applications than the average white student, but the situation is somewhat different. If he is a brilliant and exceptional student, he may be sought after, courted, seduced, bought, and before he knows it, actually auctioned
Anti-Monocyte Chemoattractant Protein-1 Gene Therapy Attenuates Renal Injury Induced by Protein-Overload Proteinuria
Authors: Hideaki Shimizu, Shoichi Maruyama, Yukio Yuzawa, Tomomi Kato, Yusuke Miki, Satoshi Suzuki, Waichi Sato, Yoshiki Morita, Hiroki Maruyama, Kensuke Egashira, Seiichi Matsuo
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. It has been postulated that protein filtered through glomeruli activates tubular epithelial cells, which secrete vasoactive and inflammatory substances including chemokines, leading to tubulointerstitial renal injury. The present study was designed to investigate the role of monocyte chemoattractant protein-1 (MCP-1) in this process and to evaluate the effectiveness of a kidney-targeted gene transfer technique using hydrodynamic pressure. Naked plasmid encoding 7ND (an MCP-1 antagonist) or a control plasmid was introduced into the left kidney of rats. Three days after gene transfer (day 0), intraperitoneal administration of bovine serum albumin (10 mg/g body wt per day) was started and continued for 14 or 21 d. RT-PCR showed that 7ND mRNA was expressed only in the gene-transfected kidney. Immunostaining showed that 7ND protein was localized in the interstitial cells. Macrophage infiltration was significantly reduced in the left kidney of rats treated with 7ND on days 14 and 21. In the right kidney, such effects were not observed. 7ND also attenuated tubular damage and decreased the number of apoptotic cells. Computer-assisted analysis revealed that the areas positively stained for α-smooth muscle actin (αSMA), fibronectin-EDA, type I collagen, and collagen fibrils were significantly reduced in the 7ND-treated kidney on day 21. Furthermore, 7ND gene therapy significantly reduced MCP-1 and TGF-β1 mRNA expression. These results demonstrate that MCP-1 plays an important role in the development of tubulointerstitial inflammation, tubular damage, and fibrosis induced by proteinuria. The fact that 7ND gene therapy had little effect on the contralateral kidney indicates that 7ND acted locally. This strategy may have a potential usefulness as a gene therapy against tubulointerstitial renal injury. E-mail: [email protected]
TGF-β Modulates Ovarian Cancer Invasion by Upregulating CAF-Derived Versican in the Tumor Microenvironment
Authors: Tsz-Lun Yeung, Cecilia S. Leung, Kwong-Kwok Wong, Goli Samimi, Melissa S. Thompson, Jinsong Liu, Tarrik M. Zaid, Sue Ghosh, Michael J. Birrer, Samuel C. Mok
Journal: Cancer Research (2013)

TGF-β has limited effects on ovarian cancer cells, but its contributions to ovarian tumor growth might be mediated through elements of the tumor microenvironment. In the present study, we tested the hypothesis that TGF modulates ovarian cancer progression by modulating the contribution of cancer-associated fibroblasts (CAF) that are present in the microenvironment. Transcriptome profiling of microdissected stromal and epithelial components of high-grade serous ovarian tumors and TGF-β-treated normal ovarian fibroblasts identified versican (VCAN) as a key upregulated target gene in CAFs. Functional evaluations in coculture experiments showed that TGF-β enhanced the aggressiveness of ovarian cancer cells by upregulating VCAN in CAFs. VCAN expression was regulated in CAFs through TGF-β receptor type II and SMAD signaling. Upregulated VCAN promoted the motility and invasion of ovarian cancer cells by activating the NF-κB signaling pathway and by upregulating expression of CD44, matrix metalloproteinase-9, and the hyaluronan-mediated motility receptor. Our work identified a TGF-β-inducible gene signature specific to CAFs in advanced high-grade serous ovarian tumors, and showed how TGF-β stimulates ovarian cancer cell motility and invasion by upregulating the CAF-specific gene VCAN. These findings suggest insights to develop or refine strategies for TGF-β-targeted therapy of ovarian cancer.
Estimation of IgM rheumatoid factors by fluorimetry.
Authors: D J Lea, D J Ward
Journal: Annals of the Rheumatic Diseases (1978)

Sheep red cells coated with rabbit IgG antibody may be used to detect IgM rheumatoid factors either by agglutination or microscopically by the fluorescence of antihuman IgM antibody conjugate bound to rheumatoid factors on the cell surface. By substituting for red cells the plastic surface of a filter disc coated with rabbit IgG it was possible to elute the bound conjugate and measure the fluorescence in a fluorimeter. The results of both the sheep cell agglutination test and the fluorescence test agreed quite well for the majority of sera; both tests seemed to reflect IgM rheumatoid factor concentrations in these sera. The difficulties encountered in attempting to define and measure accurately rheumatoid factor concentrations in a serum are emphasised.
Remarks ON THE OPERATIVE TREATMENT OF ULCER OF THE STOMACH AND ITS CHIEF COMPLICATIONS, With Indications, Limitations, and Ultimate Results
Authors: A. W. M. Robson
Journal: BMJ (1906)

AN experience of nearly 600 operations on the stomach for various diseases, together with observations on a large number of cases in which no operation was performed, has naturally given me much material for study, on which I have, rightly or wrongly, based certain definite opinions, and the only difficulty I now find is how to condense into a short paper the points most appropriate for a useful dis- cussion; for it is manifestly impossible in one, or even in two or three meetings to fully consider and discuss the indications, limitations, and ultimate results of operations -for all the non malignant diseases that may call for surgical treatment, as this would involve a consideration of acute and chronic ulcers, with their complications-per-(oration, haemorrhage, hour-glass contraction, cicatricial etenosis, and dilatation of the stomach, perigastritis with adhesions, perigastric abscess, inflammatory tumours, fistula, etc.-as well as the subjects of gastroptosis, acute and atonic dilatation, gastric tetany, pyloric and cardiac spasm, congenital hypertrophic stenosis, and other important diseases.
Assay of methylmalonic acid in the serum of patients with cobalamin deficiency using capillary gas chromatography-mass spectrometry.
Authors: S P Stabler, P D Marcell, E R Podell, R H Allen, J Lindenbaum
Journal: Journal of Clinical Investigation (1986)

To determine the incidence of elevated levels of serum methylmalonic acid in patients with cobalamin deficiency, we utilized a new capillary gas chromatographic-mass spectrometric technique to measure methylmalonic acid in the serum of 73 patients with clinically confirmed cobalamin deficiency. Values ranged from 55 to 22,300 ng/ml, and 69 of the 73 patients had values above the normal range of 19-76 ng/ml as determined for 50 normal blood donors. In the cobalamin-deficient patients, serum methylmalonic acid was significantly correlated with the serum folate level and the degree of neurologic involvement. Some patients with pernicious anemia who were intermittently treated with cyanocobalamin were found to have elevated serum levels of methylmalonic acid while free of hematologic and neurologic abnormalities. A cobalamin-deficient patient is described with a normal serum cobalamin and an elevated serum methylmalonic acid. We conclude that the ability to measure methylmalonic acid in human serum will be useful in studies designed to determine the incidence of cobalamin deficiency in various patient populations.
Extensive Left Ventricular Remodeling Does Not Allow Viable Myocardium to Improve in Left Ventricular Ejection Fraction After Revascularization and Is Associated With Worse Long-Term Prognosis
Authors: Jeroen J. Bax, Arend F.L. Schinkel, Eric Boersma, Abdou Elhendy, Vittoria Rizzello, Alexander Maat, Jos R.T.C. Roelandt, Ernst E. van der Wall, Don Poldermans
Journal: Circulation (2004)

Extensive left ventricular (LV) remodeling may not allow functional recovery after revascularization, despite the presence of viable myocardium.Seventy-nine consecutive patients with ischemic cardiomyopathy (left ventricle ejection fraction [LVEF] 29+/-7%) underwent surgical revascularization. Before revascularization, viability was assessed by metabolic imaging with F18-fluorodeoxyglucose and SPECT. LV volumes and LVEF were assessed by resting echocardiography. LVEF was re-assessed by echocardiography 8 to 12 months after revascularization. Three-year clinical follow-up (events: cardiac death, infarction, and hospitalization for heart failure) was also obtained. Forty-nine patients had substantial viability; 5 died before re-assessment of LVEF. Of the remaining 44 patients, 24 improved > or =5% in LVEF after revascularization, whereas 20 did not improve in LVEF. LV end-systolic volume was the only parameter that was significantly different between the groups (109+/-46 mL for the improvers versus 141+/-31 mL for the nonimprovers; P<0.05). The change in LVEF after revascularization was linearly related to the baseline LV end-systolic volume, with a higher LV end-systolic volume associated with a low likelihood of improvement in LVEF after revascularization. During the 3-year follow-up, the highest event-rate (67%) was observed in patients without viable myocardium with a large LV size, whereas the lowest event rate (5%) was observed in patients with viable myocardium and a small LV size. Intermediate event rates were observed in patients with viable myocardium and a large LV size (38%), and in patients without viable myocardium and a small LV size (24%).Extensive LV remodeling prohibits improvement in LVEF after revascularization and affects long-term prognosis negatively, despite the presence of viability.
Physiological Properties of hERG 1a/1b Heteromeric Currents and a hERG 1b-Specific Mutation Associated With Long-QT Syndrome
Authors: Harinath Sale, Jinling Wang, Thomas J. O'Hara, David J. Tester, Pallavi Phartiyal, Jia-Qiang He, Yoram Rudy, Michael J. Ackerman, Gail A. Robertson
Journal: Circulation Research (2008)

Cardiac I Kr is a critical repolarizing current in the heart and a target for inherited and acquired long-QT syndrome (LQTS). Biochemical and functional studies have demonstrated that I Kr channels are heteromers composed of both hERG 1a and 1b subunits, yet our current understanding of I Kr functional properties derives primarily from studies of homooligomers of the original hERG 1a isolate. Here, we examine currents produced by hERG 1a and 1a/1b channels expressed in HEK-293 cells at near-physiological temperatures. We find that heteromeric hERG 1a/1b currents are much larger than hERG 1a currents and conduct 80% more charge during an action potential. This surprising difference corresponds to a 2-fold increase in the apparent rates of activation and recovery from inactivation, thus reducing rectification and facilitating current rebound during repolarization. Kinetic modeling shows these gating differences account quantitatively for the differences in current amplitude between the 2 channel types. Drug sensitivity was also different. Compared to homomeric 1a channels, heteromeric 1a/1b channels were inhibited by E-4031 with a slower time course and a corresponding 4-fold shift in the IC50. The importance of hERG 1b in vivo is supported by the identification of a 1b-specific A8V missense mutation in 1/269 unrelated genotype-negative LQTS patients that was absent in 400 control alleles. Mutant 1bA8V expressed alone or with hERG 1a in HEK-293 cells dramatically reduced 1b protein levels. Thus, mutations specifically disrupting hERG 1b function are expected to reduce cardiac I Kr and enhance drug sensitivity, and represent a potential mechanism underlying inherited or acquired LQTS.
Sinus Node Re-entry
Authors: ONKAR S. NARULA
Journal: Circulation (1974)

Data in 20 patients with normal sinus rhythm who, following induced premature atrial beats (PABs), manifested re-entry in the region of the sinus node are presented. PABs at coupling intervals ranging between 230-535 msec were followed by sinus node re-entry (SNR). Several criteria were applied to diagnose SNR: the temporal sequence of atrial excitation, the intra-atrial conduction time, the shape and polarity of the P waves, and manifestation of re-entry independent of atrioventricular (A-V) nodal delays. In 18 patients SNR lasting for one to several beats was observed. In the remaining two patients sustained SNR was manifested as supraventricular tachycardia (SVT), with cycle lengths ranging between 320-500 msec, which persisted for several minutes prior to its termination by properly timed atrial stimuli. In one of the latter two patients sustained SNR and SVT were produced only after atropine administration. Sinus node re-entry could be elicited at will in a specific echo zone with a duration ranging between 10-170 msec. In some cases SNR was also observed during and on cessation of regular atrial pacing. The latter observation provides a possible explanation for the unexpected sinus node acceleration seen sometimes on termination of atrial pacing. It is demonstrated that SNR for a single beat may fallaciously simulate sinus node entrance block. Simultaneous occurrence of re-entry at multiple sites, i.e., the sinus node and the A-V node, with resultant fusion P waves is also demonstrated. This study provides another mechanism for the genesis of regular and irregular SVT. The analysis and localization of the re-entry circuit may prove to be of clinical and therapeutic significance in selected patients.
HLA-A*3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans
Authors: Mark McCormack, Ana Alfirevic, Stephane Bourgeois, John J. Farrell, Dalia Kasperavičiūtė, Mary Carrington, Graeme J. Sills, Tony Marson, Xiaoming Jia, Paul I.W. de Bakker, Krishna Chinthapalli, Mariam Molokhia, Michael R. Johnson, Gerard D. O'Connor, Elijah Chaila, Saud Alhusaini, Kevin V. Shianna, Rodney A. Radtke, Erin L. Heinzen, Nicole Walley, Massimo Pandolfo, Werner Pichler, B. Kevin Park, Chantal Depondt, Sanjay M. Sisodiya, David B. Goldstein, Panos Deloukas, Norman Delanty, Gianpiero L. Cavalleri, Munir Pirmohamed
Journal: New England Journal of Medicine (2011)

Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS–TEN) in the Han Chinese and other Asian populations but not in European populations.
Acute lower respiratory tract infections in HIV-infected African children - A paucity of bronchiolitis
Authors: Salome Abbott, Alicia Annamalay, Joelene Bizzintino, Siew-Kim Khoo, Peter Le Souef, Robin Green
Journal: European Respiratory Journal (2013)

Rationale  Acute lower respiratory tract infections (ALRI) contributes largely to the global burden of childhood disease, particularly in developing countries. This is due to HIV and poor socio-economic circumstances. The clinical diagnosis of viral pneumonia has been made more frequently than bronchiolitis among HIV-infected children previously. The role of HIV in ALRI is not well understood. We aim to describe the clinical symptoms and environmental risks associated with ALRI in children in South Africa.  Methods  Children less than 2 years admitted to hospital with an ALRI were enrolled. Healthy controls were included. A clinical diagnosis of pneumonia or bronchiolitis was made by the study doctor. Information on symptoms and environmental factors were collected. Diagnosis of HIV was made using ELISA tests and confirmed with a PCR for children less than 18 months.  Results  106 symptomatic and 54 controls were recruited. Of the 106 children with an ALRI, 58 (54.7%) had pneumonia and 48 (45.3%) bronchiolitis. Of the 15 (14.2%) HIV-infected children, there were more pneumonia compared with bronchiolitis cases (93.3% vs. 6.7%, p  Conclusion  Pneumonia is more common than bronchiolitis in HIV-infected children, suggesting that there is a protection conferred by HIV infection on bronchiolitis. This needs further investigation.
Lung function in the elderly.
Authors: M L Burr, K M Phillips, D N Hurst
Journal: Thorax (1985)

Data are presented on the FEV1 and forced vital capacity (FVC) of elderly people living at home. These were derived from a survey of 418 persons over the age of 70 years and thus provide standards for the assessment of elderly persons. There was a decline in FEV1 and FVC cross sectionally with age and a continued adverse effect of smoking. A history of cough and phlegm was strongly related to impairment of lung function.