tbuckley/cabot-search huggingface dataset:
Hypertension impairs myocardin function: a novel mechanism facilitating arterial remodelling
Authors: Larissa Pfisterer, Anja Feldner, Markus Hecker, Thomas Korff
Journal: Cardiovascular Research (2012)

Hypertension evokes detrimental changes in the arterial vessel wall that facilitate stiffening and thus lead to a further rise in mean blood pressure, eventually causing heart failure. The underlying pathophysiological remodelling process is elicited by an increase in wall stress (WS) and is strictly dependent on the activation of vascular smooth muscle cells (SMC). However, it remains unclear as to why these cells fail to maintain their contractile and quiescent phenotype in a hypertensive environment. In this context, we reveal that the knockdown of myocardin—a pivotal transcriptional determinant of the contractile SMC phenotype—is sufficient to induce SMC proliferation. In line with this observation, immunofluorescence analysis of the media of remodelling arteries from hypertensive mice demonstrated a significant decrease in the abundance of myocardin and an increase in SMC proliferation. Subsequent analyses of isolated perfused mouse arteries and human cultured SMCs exposed to cyclic stretch (i.e. mimicking one component of WS) suggested that this biomechanical force facilitates serine phosphorylation of myocardin. Furthermore, this biomechanical stimulus promotes rapid translocation of myocardin from the nucleus to the cytoplasm, inhibits its mRNA expression, and causes proteasomal degradation of the cytoplasmic protein. Collectively, these findings suggest that hypertension negates the activity of myocardin in SMCs on multiple levels, hence eliminating a crucial determinant of SMC quiescence. This mechanism may control the initial switch from the contractile towards the synthetic SMC phenotype during hypertension and may offer an interesting novel approach to prevent cardiovascular disease.
Abstract 5190: Detection of radioresistant gene of esophageal cancer by the new cyclopedic gene analysis with transposon
Authors: Tomoko Takesue
Journal: Cancer Research (2014)

Abstract Backgound Radiation is one of the most important therapies same as operation and chemotherapy for esophageal cancer. However a rate of therapeutic effect is low, 68.3% as a chemoradiation therapy for advanced esophageal cancer in Japan. Predicting an effect before radiation therapy is impossible, many patients suffer from side effect of radiation without enough therapeutic effect. To predict and improve an effect, it is need to identify genes and mechanism of radioresistance. Aim of this research is to detect radioresistant gene of esophageal cancer by the new cyclopedic gene analysis with transposon. Methods Transposon is a base sequence which transports to other location in the genome at random. Inserting CMV promotor to transposon as a transcriptional activator, the following gene of transported transposon is overexpressed and the gene inserted transposon is knocked down. We can get various cells which have a different overexpressed or knocked down gene by transposon method. After drug treatment or irradiation for cells inserted transposon and CMV promotor, named transposon tagged cells, survived cells have overexpressed redioresistant genes or knocked down radiosensitive genes. We can pick up candidate redioresistant genes to detect the location of transposon in survived cells. We have already succeeded to acquire candidate chemoresistant genes of breast cancer and esophageal cancer. Results Twenty days after irradiation of 9 to 11 Gy for transposon tagged cells, survived cells became colonies. Picking up survived colonies and analyzing its gene, nine genes were detected as a candidate gene. All genes were knocked down by inserting the transposon. Knock down of candidate genes were demonstrated by decreasing an amount of mRNA in survived colonies. Cells of survived colonies also showed higher survival rate after irradiation than the rate of parent esophageal cancer cells without transposon. These results mean that knocking down of the candidate gene relates to redioresistance actually. Cytochrome c oxidase subunit 1 is one of the gene detected by transposon method. Cytochrome c oxidase 1 is known as an enzyme of Cytochrome c which induce apoptosis after DNA damage from radiation by activating caspase cascade. This fact supports that knock down of cytochrome c oxidase 1 may suppress release of cytochrome c and then radiation induced apoptosis. Conclusion Transposon method is able to analyze resistant genes comprehensively. To reveal resistant mechanism of detected gene, new target of treatment may be found. Citation Format: Tomoko Takesue. Detection of radioresistant gene of esophageal cancer by the new cyclopedic gene analysis with transposon. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5190. doi:10.1158/1538-7445.AM2014-5190
Time—A Brief Fantasy
Authors: Irwin M. Siegel
Journal: JAMA (1982)

They are old, so very, very aged, and they keep growing older.  But Doctor, why am I in pain?   simply the aging process. Not a disease, you understand, just a physiological decline. You might call it gray hair of the joints.  But Doctor, what can I do about it?  Aspirin, heat, rest, not much else. It's the price you pay for senior citizenry.  But Doctor, I didn't have the pain and stiffness last week. I never felt like this before, why now?  The nonacceptance of aging. The bewilderment at how quickly it happened. The endless questioning. The routine visits from month to month. Prescribing enough aspirin to reach the moon, advising sufficient hot baths to fill an ocean, recommending rest enough to take a lifetime.  Moving from examining room to examining room all afternoon, like touring a museum of what has become. Attempting to stimulate interest, going on automatic
P2-203: Cisplatin/Gemcitabine followed by Cisplatin/Etoposide and concurrent thoracic radiotherapy in patients with irresectable or medically inoperable non-small-cell lung cancer
Authors: Erik C. Phernambucq, Femke O. Spoelstra, Suresh Senan, Marinus A. Paul, Christian F. Melissant, Pieter E. Postmus, Egbert F. Smit
Journal: Journal of Thoracic Oncology (2007)
Leptin inhibits insulin secretion by activation of phosphodiesterase 3B.
Authors: A Z Zhao, K E Bornfeldt, J A Beavo
Journal: Journal of Clinical Investigation (1998)

The molecular signaling events by which leptin exerts its functions in vivo are not well delineated. Here, we show a novel leptin signaling mechanism that requires phosphoinositide 3-kinase (PI 3-kinase)-dependent activation of cyclic nucleotide phosphodiesterase 3B (PDE3B) and subsequent suppression of cAMP levels. In pancreatic beta cells, leptin causes the activation of PDE3B, which leads to marked inhibition of glucagon-like peptide-1-stimulated insulin secretion. The effect of leptin is abolished when insulin secretion is induced with cAMP analogues that cannot be hydrolyzed by PDE3B. Selective inhibitors of PDE3B and PI 3-kinase completely prevent the leptin effect on insulin secretion and cAMP accumulation. The results demonstrate that one of the physiological effects of leptin, suppression of insulin secretion, is mediated through activation of PDE3B and suggest PDE3B as a mediator of leptin action in other tissues.
Elemental changes in guinea-pig epidermis in the hyperplastic response to irritant stimuli
Authors: M. LINDBERG, T.G. GRUNDIN
Journal: British Journal of Dermatology (1987)

A mild irritant reaction was induced by application of sodium lauryl sulphate to the skin of guinea-pigs. The response was analysed at 24 and 48 h after application using light microscopy, transmission electron microscopy and energy dispersive X-ray microanalysis (EDX). It was found that the sodium lauryl sulphate induced a hyperplastic response in the epidermis with an increased number of keratinocytes. This response was associated with significantly increased levels of intracellular sodium and chloride. The elemental changes were most marked at 24 h, whereas the number of keratinocytes was highest at 48 h. The pattern of the elemental changes and the ultrastructural alterations are compatible with initial membrane damage followed by a transient increase in proliferative activity. The present results demonstrate that EDX is a useful tool for the analysis of functional alterations in epidermal keratinocytes under pathological conditions.
Primary iron overload with inappropriate hepcidin expression in V162del ferroportin disease
Authors: Heinz Zoller, Ian McFarlane, Igor Theurl, Sylvia Stadlmann, Elizabeta Nemeth, David Oxley, Tomas Ganz, David J. Halsall, Timothy M. Cox, Wolfgang Vogel
Journal: Hepatology (2005)

Ferroportin disease (hemochromatosis type 4) is a recently recognized disorder of human iron metabolism, characterized by iron deposition in macrophages, including Kupffer cells. Mutations in the gene encoding ferroportin 1, a cellular iron exporter, are responsible for this iron storage disease, inherited as an autosomal dominant trait. We present clinical, histopathological, and radiological findings in a family with the most common ferroportin mutation, V162del. In the index case, the disorder is characterized by abundant deposition of hemosiderin in all tissues investigated (mesenteric lymph node, liver, gastric and duodenal mucosa, and also in squamous cell carcinoma of the lung). The radiological findings indicated the presence of excess iron in bone marrow and spleen. Despite a significant burden of iron, no features of chronic liver disease were found in affected members of the family, including individuals aged up to 80 years. Hyperferritinemia greater than 1,000 microg/L was a penetrant biochemical finding before the second decade in life and was associated with significantly increased serum concentrations of pro-hepcidin that correlated positively with urinary hepcidin concentrations. In conclusion, the systemic iron burden in ferroportin disease is not a sufficient cause for chronic liver disease. In patients with most, but not all, ferroportin mutations, retention of iron in macrophages of the liver and other organs may protect against damage to parenchymal cells. Finally, macrophage iron storage in ferroportin disease is associated with elevated serum pro-hepcidin levels.
Managing the Interface Between Medical Schools, Hospitals, and Clinical Research
Authors: John I. Gallin
Journal: JAMA (1997)

To review how academic health centers are coping with the changing environment of health care delivery with special emphasis on the impact of the changing health care system on clinical research.In response to Health and Human Services Secretary Donna Shalala's 1995 mandated review of the National Institutes of Health (NIH) Warren Grant Magnuson Clinical Center, an NIH review team visited 30 health facilities and government-owned organizations throughout the country. The review team determined what strategies are used by academic health centers to survive and thrive in the changing health care marketplace. The findings have implications for the NIH Clinical Center as well as academic health centers.Management strategies in successful academic health centers include streamlined governance structures whereby small groups of highly empowered group leaders allow institutions to move quickly and decisively; an active strategic planning process; close integration of hospital and medical school management; heavy investment in information systems; and new structures for patient care delivery. Successful centers are initiating discussions with third-party payers and are implementing new initiatives, such as establishing their own managed care organizations, purchasing physician practices, or owning hospitals. Other approaches include establishing revenue-generating centers for clinical research and new relations with industry. Attention to the infrastructure required to support the training and conduct of clinical research is essential for the future vitality of medical schools.
Heterozygous MZ Alpha1-Antitrypsin Deficiency in Adults with Chronic Active Hepatitis and Cryptogenic Cirrhosis
Authors: John R. Hodges, G. H. Millward-Sadler, C. Barbatis, Ralph Wright
Journal: New England Journal of Medicine (1981)

To determine the prevalence of alpha1-antitrypsin deficiency in patients with cirrhosis or chronic active hepatitis, we performed a five-year prospective study of liver-biopsy specimens from 1055 adults. Thirty-four patients whose specimens contained hepatocyte inclusions characteristic of the deficiency were phenotyped, and 25 had phenotype MZ (2.4 per cent). The distribution of patients with this phenotype among the 185 patients with cirrhosis diagnosed histologically was three of 84 patients with alcoholic cirrhosis (3.5 per cent), seven of 34 with non-B chronic active hepatitis (20.5 per cent), six of 28 with cryptogenic cirrhosis (21 per cent), and one of 39 with other kinds of cirrhosis (2.6 per cent). The increased prevalence of MZ in patients with cryptogenic cirrhosis and with chronic active hepatitis is highly significant (P<0.001). Because serum levels of alpha1-antitrypsin may be unreliable for identification of the subgroup of patients with chronic active hepatitis or cryptogenic cirrhosis, analysis of serum for the MZ phenotype and meticulous examination of biopsy specimens may be necessary. (N Engl J Med. 1981; 304:557–60.)
The APOC3 T-455C and C-482T promoter region polymorphisms are not associated with the severity of liver damage independently of PNPLA3 I148M genotype in patients with nonalcoholic fatty liver
Authors: Luca Valenti, Valerio Nobili, Ahmad Al-Serri, Raffaela Rametta, Julian B.S. Leathart, Marco A. Zappa, Paola Dongiovanni, Anna L. Fracanzani, Arianna Alterio, Giancarlo Roviaro, Ann K. Daly, Silvia Fargion, Christopher P. Day
Journal: Journal of Hepatology (2011)
Characterization of the Peri-Infarct Zone by Contrast-Enhanced Cardiac Magnetic Resonance Imaging Is a Powerful Predictor of Post–Myocardial Infarction Mortality
Authors: Andrew T. Yan, Adolphe J. Shayne, Kenneth A. Brown, Sandeep N. Gupta, Carmen W. Chan, Tuan M. Luu, Marcelo F. Di Carli, H. Glenn Reynolds, William G. Stevenson, Raymond Y. Kwong
Journal: Circulation (2006)

Background— Accurate risk stratification is crucial for effective treatment planning after myocardial infarction (MI). Previous studies suggest that the peri-infarct border zone may be an important arrhythmogenic substrate. In this pilot study, we tested the hypothesis that the extent of the peri-infarct zone quantified by contrast-enhanced cardiac magnetic resonance (CMR) is an independent predictor of post-MI mortality. Methods and Results— We studied 144 patients with documented coronary artery disease and abnormal myocardial delayed enhancement (MDE) consistent with MI. A computer-assisted, semiautomatic algorithm quantified the total infarct size and divided it into the core and peri-infarct regions based on signal-intensity thresholds (&gt;3 SDs and 2 to 3 SDs above remote normal myocardium, respectively). The peri-infarct zone was normalized as a percentage of the total infarct size (%MDE periphery ). After a median follow-up of 2.4 years, 29 (20%) patients died. Patients with an above-median %MDE periphery were at higher risk for death compared with those with a below-median %MDE periphery (28% versus 13%, log-rank P &lt;0.01). Multivariable analysis showed that left ventricular systolic volume index and %MDE periphery were the strongest predictors of all-cause mortality (adjusted hazard ratio [HR] for %MDE periphery , 1.45 per 10% increase; P =0.002) and cardiovascular mortality (adjusted HR, 1.51 per 10% increase; P =0.009). Similarly, after adjusting for age and left ventricular ejection fraction, %MDE periphery maintained strong and independent associations with all-cause mortality (adjusted HR, 1.42; P =0.005) and cardiovascular mortality (adjusted HR, 1.49; P =0.01). Conclusions— In patients with a prior MI, the extent of the peri-infarct zone characterized by CMR provides incremental prognostic value beyond left ventricular systolic volume index or ejection fraction. Infarct characteristics by CMR may prove to be a unique and valuable noninvasive predictor of post-MI mortality.
The Care of the Rheumatoid Hand
Authors: John G. Kuhns
Journal: JAMA (1964)

In this book the author reaffirms what many students of arthritis have long suspected: if satisfactory function is to be preserved or regained in the hand disabled by rheumatoid arthritis, treatment must be begun early and surgical correction cannot long be delayed. This is a useful, timely book. It advances our understanding of the repair and rehabilitation of the rheumatoid hand as far as we should go until we have learned more about the permanence of these procedures. In our present ignorance it is probably arrant nonsense, as the author states, to delay surgery until the sedimentation rate falls and the inflammation abates. A description of the pathological changes and a kinesiology of the hand muscles prepare the reader for a discussion of the operative procedures. These are illustrated with many excellent photographs. In the early surgical treatment as complete a removal as possible of the inflamed synovial tissue is
463 ACHIEVEMENT OF RIBAVIRIN CUT-OFF BY MONITORING PLASMA CONCENTRATIONS BUT NOT HAEMOGLOBIN DROP IS PREDICTIVE OF SUSTAINED VIROLOGICAL RESPONSE IN PATIENTS WITH CHRONIC HEPATITIS C
Authors: S. Piedoux, E. Monnet, L. Piroth, D. Montange, B. Royer, T. Thevenot, J.P. Kantelip, V. Di Martino, P. Muret
Journal: Journal of Hepatology (2011)
Hypophysectomy as Palliative Treatment
Authors: Bronson S. Ray
Journal: JAMA (1967)

Since the majority of women with breast cancer eventually develop dissemination of their disease despite radical mastectomy and radiation therapy, palliative treatment takes on great importance. Appropriate endocrine therapy, including ablative procedures, may provide an effective means for not only relief of symptoms, but in many cases, a temporary arrest of the growth of the cancer with prolongation of useful and comfortable life. The recognition that alteration in the endocrine state of the body might have a salutary effect in the control of breast cancer is credited to Beatson<sup>6</sup>who employed oophorectomy in premenopausal women for this purpose. It has been found that the procedure is effective in causing remission of the disease for an average of nine months in about 33% of patients. As a result of this and other experiences in the study of factors in breast cancer in both humans and laboratory animals, the tumor has
Attenuated response of L-type calcium current to nitric oxide in atrial fibrillation
Authors: Nadiia Rozmaritsa, Torsten Christ, David R. Van Wagoner, Hannelore Haase, Johannes-Peter Stasch, Klaus Matschke, Ursula Ravens
Journal: Cardiovascular Research (2013)

Nitric oxide (NO) synthesized by cardiomyocytes plays an important role in the regulation of cardiac function. Here, we studied the impact of NO signalling on calcium influx in human right atrial myocytes and its relation to atrial fibrillation (AF). Right atrial appendages (RAAs) were obtained from patients in sinus rhythm (SR) and AF. The biotin-switch technique was used to evaluate endogenous S-nitrosylation of the α1C subunit of L-type calcium channels. Comparing SR to AF, S-nitrosylation of Ca2+ channels was similar. Direct effects of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) on L-type calcium current (ICa,L) were studied in cardiomyocytes with standard voltage-clamp techniques. In SR, ICa,L increased with SNAP (100 µM) by 48%, n/N = 117/56, P < 0.001. The SNAP effect on ICa,L involved activation of soluble guanylate cyclase and protein kinase A. Specific inhibition of phosphodiesterase (PDE)3 with cilostamide (1 µM) enhanced ICa,L to a similar extent as SNAP. However, when cAMP was elevated by PDE3 inhibition or β-adrenoceptor stimulation, SNAP reduced ICa,L, pointing to cGMP–cAMP cross-regulation. In AF, the stimulatory effect of SNAP on ICa,L was attenuated, while its inhibitory effect on isoprenaline- or cilostamide-stimulated current was preserved. cGMP elevation with SNAP was comparable between the SR and AF group. Moreover, the expression of PDE3 and soluble guanylate cyclase was not reduced in AF. NO exerts dual effects on ICa,L in SR with an increase of basal and inhibition of cAMP-stimulated current, and in AF NO inhibits only stimulated ICa,L. We conclude that in AF, cGMP regulation of PDE2 is preserved, but regulation of PDE3 is lost.
Expression profiling of suppressive monocytes (CD14+HLA-DRlow/neg) in cancer patients
Authors: Stefan F Cordes, Michael P Gustafson, Zhe Zhang, Peggy A Bulur, Dennis A Gastineau, Yi Lin, Allan B Dietz
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Immune evasion by suppression of host immunity is one of the major mechanisms that tumors use to promote its own survival. We have reported an abundance of immunosuppressive monocytes (CD14+HLA-DRlow/neg) in lymphoma (LYM), multiple myeloma (MM), glioblastoma multiforme (GBM),
Internal Fixation by the Ender Method
Authors: L. Arne Skilbred
Journal: JAMA (1979)

To the Editor.—  The article Internal Fixation by the Ender Method by Corzatt and Bosch (240:1366, 1978), presents an alternative and new method for fixation of intertrochanteric fractures of the hip. I studied this method while on a sabbatical in Europe and agree with the authors on the biomechanical advantage that this method offers. However, our experience in using this method in our 450-bed hospital on a small group of patients has not been entirely satisfactory.  Follow-up at 12 to 24 months in a group of nine patients with an average age of 85 years showed an average blood loss of 8.5 percentage points on hematocrit readings and blood replacement averaging 2 units. The blood loss usually became apparent about two days after the surgery, possibly from bleeding occurring into the intramedullary cavity. Operating time for the Ender method averaged 48 minutes using an image intensifier, which is a requirement
Surgical Principles of Resection and Reconstruction
Authors: John T. Goodner
Journal: JAMA (1974)

Cancer of the esophagus usually has a bad prognosis, primarily because the diagnosis is made late, and localized disease is not seen frequently. The esophagus is a muscular tube that dilates in the presence of gradual, partial obstruction, which does not produce symptoms until some time has elapsed. The patient frequently does not see his physician until he has had dysphagia for a long period of time, or until complete obstruction has occurred. It is surprising how long patients will tolerate dysphagia of a mild-to-moderate degree, limiting themselves to a soft or semiliquid diet before they seek help. The actual occurrence of dysphagia is a late symptom in cancer of the esophagus. Pain in the retrosternal region usually results from the attempt to swallow food past a partial or almost complete obstruction. Radiating pain, or pain in the back usually indicates extension of disease outside the limits of the esophagus,
Creamatocrit: simple clinical technique for estimating fat concentration and energy value of human milk.
Authors: A Lucas, J A Gibbs, R L Lyster, J D Baum
Journal: BMJ (1978)

A simple micromethod has been devised for estimating the fat and energy content of human milk based on the centrifugation of milk in a haematocrit centrifuge. The percentage of cream, or "creamatocrit," is read from the haematocrit capillary tube and is linearly related to the fat and energy content. The technique, which is rapid and cheap, may be used in clinical practice, in research, and in epidemiological studies.