tbuckley/cabot-search huggingface dataset:
Characterization of muscarinic acetylcholine receptors expressed by an atrial cell line derived from a transgenic mouse tumor.
Authors: M E Morton, C Brumwell, C L Gartside, S D Hauschka, N M Nathanson
Journal: Circulation Research (1994)

The properties of muscarinic acetylcholine receptors in the cell line MCM1, derived from an SV40 T-antigen-induced atrial tumor in a transgenic mouse, were determined. Binding studies using the nonselective muscarinic antagonist [3H]quinuclidinyl benzilate, the M1-selective antagonist pirenzepine, and the M2-selective antagonist AFDX-116 indicate that the receptors have the pharmacological properties of the cardiac (M2) receptor subtype. The receptors could be immunoprecipitated with a monoclonal antibody specific for the cardiac receptor, thus confirming the identity of the receptors expressed in these cells. The types of G proteins expressed in the cells were determined by Northern blot analyses: mRNA encoding the alpha subunits of Gs, G(o), and Gi-2, but not Gi-1 or Gi-3, were detected, consistent with previous observations of neonatal mammalian atria. The muscarinic receptors were functionally active, as demonstrated by the ability of the agonist to stimulate phosphoinositide turnover and to inhibit adenylyl cyclase activity. The availability of a mammalian atrial cell line that continues to express the appropriate functionally coupled subtype of muscarinic receptor may provide a useful system for the investigation of the regulation of expression and function of cardiac muscarinic receptors.
On Death and Dying: What the Dying Have to Teach Doctors, Nurses, Clergy and Their Own Families.
Authors: Elisabeth Kübler-Ross
Journal: Annals of Internal Medicine (1970)

One of the most famous psychological studies of the late twentieth century, On Death and Dying grew out of an interdisciplinary seminar on death, originated and conducted by Dr. Elisabeth Kubler-Ross. In On Death and Dying, Dr. Kubler-Ross first introduced and explored the now-famous idea of the five stages of dealing with death: denial and isolation, anger, bargaining, depression, and acceptance. With simple interviews and conversations, she gives the reader a better understanding of how iminent death affects the patient, the professionals who serve the patient, and the patient's family, bringing hope, solace, and peace of mind to all involved.
Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance.
Authors: H O Steinberg, H Chaker, R Leaming, A Johnson, G Brechtel, A D Baron
Journal: Journal of Clinical Investigation (1996)

To test the hypothesis that obesity/insulin resistance impairs both endothelium-dependent vasodilation and insulin-mediated augmentation of endothelium-dependent vasodilation, we studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of methacholine chloride (MCh) or sodium nitroprusside (SNP) during saline infusion and euglycemic hyperinsulinemia in lean insulin-sensitive controls (C), in obese insulin-resistant subjects (OB), and in subjects with non-insulin-dependent diabetes mellitus (NIDDM). MCh induced increments in LBF were approximately 40% and 55% lower in OB and NIDDM, respectively, as compared with C (P < 0.05). Euglycemic hyperinsulinemia augmented the LBF response to MCh by - 50% in C (P < 0.05 vs saline) but not in OB and NIDDM. SNP caused comparable increments in LBF in all groups. Regression analysis revealed a significant inverse correlation between the maximal LBF change in response to MCh and body fat content. Thus, obesity/insulin resistance is associated with (a) blunted endothelium-dependent, but normal endothelium-independent vasodilation and (b) failure of euglycemic hyperinsulinemia to augment endothelium-dependent vasodilation. Therefore, obese/insulin-resistant subjects are characterized by endothelial dysfunction and endothelial resistance to insulin's effect on enhancement of endothelium-dependent vasodilation. This endothelial dysfunction could contribute to the increased risk of atherosclerosis in obese insulin-resistant subjects.
1117 DELTA LIKE LIGAND4 ATTENUATES EXPERIMENTAL LIVER FIBROSIS
Authors: L. Heng, L. Yan, S. Zhe, X. Ming-Yi, M. Christoph, I. Iryna, X. Chengfu, Y. Chaohui, F. Teng, L. Qi, S. Hong, S. Carolin, Z. Xuequn, Q. Ying, M. Alexandra, M. Stefan, L. Roman, D. Ten Peter, L. Lun-Gen, L. Youming, W. Hong-Lei
Journal: Journal of Hepatology (2013)
Transplantation of Autologous Fresh Bone Marrow Into Infarcted Myocardium: A Word of Caution
Authors: Alain Bel, Emmanuel Messas, Onnik Agbulut, Patrice Richard, Jane- Lyse Samuel, Patrick Bruneval, Albert A. Hagège, Philippe Menasché
Journal: Circulation (2003)

Background— As the benefits of extemporaneous transplantation (Tx) of fresh (unfractionated) autologous bone marrow (BM) have been primarily studied in the setting of acute myocardial infarction, we assessed whether this approach could be effective for regenerating chronically infarcted myocardium. Methods and Results— Myocardial infarction was created in 18 sheep by ligation of circumflex arterial branches. Three weeks later, BM was aspirated from the iliac crest, washed, labeled with the fluorescent dye Dil and reinjected (mean: 422×10 6 cells in 3 mL) in 10 sites across the infarcted area through the reopened thoracotomy (n=9). Nine controls received culture medium. Left ventricular (LV) function was assessed before and 2 months after Tx by two-dimensional echocardiography whereas transmural velocity gradients were measured using M-mode tissue Doppler imaging at the center of the infarcted/grafted area. Formalin-fixed hearts were processed for the detection of grafted cells and angiogenesis. LV ejection fraction deteriorated similarly in the Tx and control groups (from 42±5% to 30±4% and from 40±4% to 31±1%, respectively; P =0.86). Likewise, BM Tx failed to prevent LV dilatation and impairment of the global wall motion score. The decrease in regional systolic velocity gradients (s −1 ) featured a similar pattern (Tx group: from 0.77±0.11 to 0.31±0.07; control group: from 0.73±0.10 to 0.50±0.07; P =0.06). Histologically, there was neither BM tissue engraftment, except for a few scattered Dil-positive macrophages in the infarcted fibrotic areas nor transdifferentiation of BM cells into endothelial cells. Conclusion— These data caution against the functional efficacy of extemporaneous Tx of fresh unfractionated BM into postinfarction scars.
A View of Modern Chinese Medicine
Authors: TSUNG O. CHENG
Journal: Annals of Internal Medicine (1973)

As the fifth American, but the first Chinese-born, physician to have visited China in 22 years, I recount what I saw in modern China. Chinese medicine has made great strides in the past two decades, especially in the field of cardiology, which is my main interest. The frequency of coronary artery disease is definitely on the rise. Rheumatic heart disease is still prevalent. All types of congenital heart defects have been successfully repaired by open heart surgery with Chinese-made heart-lung machines. Cardiac surgery, either open or closed, is often performed under acupunctural anesthesia. The latter is a typical example of what can be accomplished through the integration of traditional Chinese medicine and modern Western medicine. Today in China the two are combined in teaching, research, development, and patient care and work together in vigorously and effectively serving the health needs of the entire 700 million Chinese.
Downhill Skiing: Impressive to the Impressionable-Reply
Authors: Drummond Rennie
Journal: JAMA (1989)

In Reply.—  I thank Mr Berestka for his comments and for citing evidence that the risk of fatal heart attacks in skiers is extremely low. I also thank him for convincing me that downhill skiing is not an entirely anaerobic activity. Provided a downhill skier actually spends all of the 5 or 6 hours skiing rather than standing (at vantage points, in lift cabins, in lines, or at bars) or sitting (in lift chairs, at tables, on bar stools, or in snowdrifts), he or she will have had a pleasant workout and will have impressed Mr Berestka.  Meanwhile, in the same 5 or 6 hours at high altitude, the cross-country skier, the marathon runner, the high-altitude trekker, and the mountain climber with his huge pack all will have impressed me.
Clinical Studies With Cloxacillin
Authors: Marvin Turck
Journal: JAMA (1965)

A new semisynthetic penicillinase-resistant penicillin, cloxacillin, was used in treatment of 100 hospitalized patients with severe infections. Twenty-three of 25 patients with staphylococcal infections, 30 of 37 with pneumococcal infections, all 13 patients with streptococcal infection, and 17 of 25 with infection due to a variety of organisms responded favorably. At the present time, the drug is available only in oral-dosage form, limiting its use in severely ill patients. A toxic effect on the gastrointestinal tract was not observed; rashes developed in two patients. Serious superinfections occurred in at least three patients with pneumococcal pneumonia. Cloxacillin compares favorably with other semisynthetic penicillinaseresistant penicillins now available in the oral-dosage form.
Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B
Authors: Yao-Shih Hsu, Rong-Nan Chien, Chau-Ting Yeh, I-Shyan Sheen, Hung-Yi Chiou, Chia-Ming Chu, Yun-Fan Liaw
Journal: Hepatology (2002)

During the course of chronic hepatitis B virus (HBV) infection, hepatitis B e antigen (HBeAg) seroconversion to its antibody (anti-HBe) often coincides with normalization of liver biochemical test and clinical remission, but data regarding long-term outcome after spontaneous seroconversion are still scarce. Excluding patients with other virus(es) concurrent infection, 283 patients with chronic HBV infection were followed up for at least 1 year after spontaneous HBeAg seroconversion to anti-HBe. Follow-up studies included clinical, biochemical, and virologic evaluation and hepatocellular carcinoma (HCC) screening with ultrasonography and α-fetoprotein assay. During a median follow-up period of 8.6 years (range, 1 to 18.4 years) after HBeAg seroconversion in 283 patients, 189 (66.8%) showed sustained remission, whereas the remaining 94 (33.2%) experienced alanine aminotransferase (ALT) elevation over twice the upper limit of normal: 12 (4.2%) associated with HBeAg reversion, 68 (24%) with detectable serum HBV DNA but HBeAg negative, and 14 (4.9%) of undetermined causes. Of the 269 patients without evidence of cirrhosis at the time of HBeAg seroconversion, 21 (7.8%) developed cirrhosis with a cumulative incidence and relative risk significantly higher in patients developing active hepatitis than in patients with sustained remission ( P &lt; .05). HCC developed in 6 (2.2%) of the 283 patients, also with a significantly higher cumulative incidence in patients developing active hepatitis after HBeAg seroconversion ( P &lt; .005). In conclusion, the results suggest that spontaneous HBeAg seroconversion confers favorable long-term outcomes. However, active hepatitis still may develop and lead to cirrhosis and HCC.
Transgenic Mouse Model for Rapid Pharmacodynamic Evaluation of Antiandrogens
Authors: Katharine Ellwood-Yen, John Wongvipat, Charles Sawyers
Journal: Cancer Research (2006)

Abstract Persistent androgen receptor signaling has been implicated as a critical factor in prostate cancer progression even at the hormone-refractory stage and provides strong rationale for developing novel androgen receptor antagonists. Traditional models for in vivo evaluation of antiandrogens are cumbersome because they rely on physiologic end points, such as the size of androgen-dependent tissues. Here, we describe a transgenic mouse (ARR2 Pb-Lux) that expresses luciferase specifically in the prostate in an androgen-dependent fashion. This signal is reduced by castration or by treatment with bicalutamide and can be quantified through noninvasive bioluminescent imaging. ARR2 Pb-Lux mice provide a novel method for rapid pharmacodynamic evaluation of novel pharmacologic compounds designed to inhibit androgen receptor signaling. (Cancer Res 2006; 66(21): 10513-6)
NHS continues to flout rights of disabled people to health care, watchdog says
Authors: Zosia Kmietowicz
Journal: BMJ (2007)

Campaigners have repeated their call for more to be done to meet the health needs of people with learning disabilities and mental health problems—who, they say, continue to be failed by the NHS in England and Wales.

One year after its damning report into the delivery of health care to disabled people, the Disability Rights Commission, the statutory watchdog organisation for people with disabilities in England, Wales, and Scotland, says in a new report that little has changed to bridge the gap in health care.

Only two strategic health authorities in England—North East and South West—have developed adequate schemes to comply with new laws on disability equality that came into force in December 2006, says the report. Of the remaining eight authorities six have schemes that are unacceptable and two—Yorkshire and the Humber and London—have failed to address the issue of equal rights for …
Disclosure of<i>APOE</i>Genotype for Risk of Alzheimer's Disease
Authors: Robert C. Green, J. Scott Roberts, L. Adrienne Cupples, Norman R. Relkin, Peter J. Whitehouse, Tamsen Brown, Susan LaRusse Eckert, Melissa Butson, A. Dessa Sadovnick, Kimberly A. Quaid, Clara Chen, Robert Cook-Deegan, Lindsay A. Farrer
Journal: New England Journal of Medicine (2009)

The apolipoprotein E (APOE) genotype provides information on the risk of Alzheimer's disease, but the genotyping of patients and their family members has been discouraged. We examined the effect of genotype disclosure in a prospective, randomized, controlled trial.
Metabolic abnormalities in the genetically obese and diabetic Otsuka Long-Evans Tokushima fatty rat can be prevented and reversed by α-glucosidase inhibitor
Authors: Mitsuyoshi Yamamoto, Dong Mei Jia, Ken-Ichiro Fukumitsu, Issei Imoto, Yasuyuki Kihara, Yosihide Hirohata, Makoto Otsuki
Journal: Metabolism (1999)
Children's vitamin D intake should be doubled, US paediatricians say
Authors: B. Roehr
Journal: BMJ (2008)

The American Academy of Pediatrics has recommended that children under the age of 18 consume 400 IU of vitamin D a day, double the amount previously recommended.

The guidance, published in Pediatrics (doi:10.1542/peds.2008-1862) and also available on the academy’s website (www.aap.org/new/VitaminDreport.pdf), says that infants who consume at least a litre a day of formula milk fortified with vitamin D do not need supplementation. However, infants who are fully breast fed or who have mixed feeding and receive less than a litre of fortified milk a day should begin supplementation with 400 IU a day of vitamin …
Fortnightly review: Acute urinary retention in men: an age old problem
Authors: M. Emberton, K. Anson
Journal: BMJ (1999)

Acute urinary retention refers to the sudden inability to pass urine. It will often be unexpected, usually inconvenient, and always painful. If a man lives long enough his risk of having an episode of acute urinary retention is remarkably high. Over 1 in 10 men in their 70s will experience acute urinary retention within the next five years.1 The risk for men in their 80s is nearly 1 in 3. Treatment depends largely on where the episode occurred. In some areas men have catheters inserted by their general practitioners (with immediate relief of pain), in others patients have to get to hospital first.2 Once a catheter is inserted treatment depends on local policy. Some men will be sent home with a catheter and collection bag, others will spend a night or two in hospital, and a few will find themselves consenting to prostatectomy the next day.3Those sent home will have to wait to be readmitted for a trial without catheter or prostatectomy, or both (if the trial fails). Our understanding of why men develop acute urinary retention has been limited. Until recently, the only way to deal with the condition was to drain the bladder with a catheter. Over the centuries only the materials, silicone rubber instead of silver and ivory, have changed (1). However, recent developments offer hope of better treatment. Firstly, high quality experimental and community based studies have greatly improved our understanding of the epidemiology and pathogenesis of acute urinary retention. Secondly, recent reports suggest that acute urinary retention might be preventable in some men. Thirdly, development in catheter technology might substantially improve management and make hospital admission unnecessary. #### Summary points
Six-month supervised intermittent tuberculosis therapy in Haitian patients with and without HIV infection.
Authors: R E Chaisson, H C Clermont, E A Holt, M Cantave, M P Johnson, J Atkinson, H Davis, R Boulos, T C Quinn, N A Halsey
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We enrolled 427 consecutive patients with tuberculosis diagnosed in Cité Soleil, Haiti in a trial of short-course intermittent therapy. All patients received supervised therapy with isoniazid, rifampin, pyrazinamide, and ethambutol thrice weekly for 8 wk, followed by isoniazid and rifampin thrice weekly for 18 wk. At entry, the 177 human immunodeficiency virus (HIV)-infected patients (42%) were found significantly more likely to have extrapulmonary tuberculosis and negative tuberculin skin tests (p < 0.05). Treatment was well tolerated by both groups of patients, and adherence to the treatment regimen was over 90%. Among patients with pulmonary or intrathoracic tuberculosis, 9% of HIV-seropositive and 1% of HIV-seronegative patients died during therapy (p < 0.001), whereas 81% and 87%, respectively, of those in the two groups were cured. Relapses occurred in 5.4% of HIV-seropositive and 2.8% of HIV-seronegative patients who completed treatment (p = 0.36). Survival after tuberculosis was poorer in HIV-seropositive patients, whose probability of dying was 33% at 18 mo after diagnosis as compared with 3% for HIV-seronegative patients (p < 0.001). HIV-seropositive patients who died had significantly lower median CD4 lymphocyte counts than did HIV-seropositive patients who survived (p < 0.001). Treatment of tuberculosis with short-course, thrice-weekly, supervised therapy in the setting of a developing country is highly efficacious in both HIV-seropositive and -seronegative patients.
Do economic slumps increase illness?
Authors: William A. Check
Journal: JAMA (1979)

The striking decrease in mortality from cardiovascular diseases that has occurred in Western countries during the last ten years was unpredicted and has no adequate explanation. But the question continues to stir many minds. An Australian economist now reports that the decline in mortality from ischémie heart disease (IHD) in that country may be accounted for by common-sense factors not usually considered in medical discussions: improved economic conditions and decreased unemployment. Although two critiques in the same issue of the journal (<i>American Journal of Public Health</i>, August 1979) question some of the author's methods, his conclusions agree with those of a slowly growing body of data relating economic conditions to morbidity and mortality in many European and North American countries. Alfred Bunn, DSR, BCom, MEc, of the School of Economic and Financial Studies in New South Wales, carried out the analysis of Australian coronary mortality data. He found that changes in age- and sex-specific IHD mortality were highly correlated with unemployment in three time periods—the years preceding, during, and following the Great Depression, which began about 1930.
Accumulation of 8-oxo-2′-deoxyguanosine and increased expression of hMTH1 protein in brain tumors
Authors: Takashi Iida, Akiko Furuta, Masatou Kawashima, Jun-ichi Nishida, Yusaku Nakabeppu, Toru Iwaki
Journal: Neuro-Oncology (2001)

Oxidative DNA damage generated by an attack of reactive oxygen species causes mutation or cell death that may lead to various diseases and may be related to initiation or progression of carcinogenesis. 8-Oxo-2 deoxyguanosine (8-oxo-dG) is a major oxidative DNA damage product that can result in mutation, and hMTH1, human MutT homolog protein 1, has been identified as an enzyme that hydrolyzes 8-oxo-dGTP to the monophosphate, thus preventing accumulation of 8-oxo-dG in DNA. With immunohistochemical approaches, we investigated accumulation of 8-oxo-dG and expression of hMTH1 in brain tumor tissues obtained from surgical and autopsy cases, including 42 neuroepithelial tumors, 5 meningiomas, 2 metastatic brain tumors, and 1 schwannoma. 8-Oxo-dG accumulation and hMTH1 expression were increased in various brain tumors. Nuclei of brain tumor cells were immunoreactive for 8-oxo-dG in all cases. In most cases, both nuclei and cytoplasm of the tumor cells were immunoreactive for hMTH1. Both 8-oxo-dG accumulation and hMTH1 expression were most evident in high-grade gliomas, indicating that oxidative stress was high in these gliomas. Thus, the defense mechanism against such oxidative stress may be enhanced as well. These results suggest that oxidative stress may play a role in tumor progression.
Clinical Records of the Lock Hospital
Authors: H. Lee
Journal: BMJ (1861)

When the IF there be one pathological fact that has been perly inocu.more frequently reiterated of late years than an-ing to hin ] other, it is, that a prinmary syphilitic sore may be the first tw; distinguished from every other affection by its secre-comes red ; tion, when inoculated, invariably producing the cha-secretion be racteristic syphilitic pustule.Although syphilitic depression i inoculation was practised by Hunter and other accu-poxa is ful rate observers, it remained for Ricord to draw well-The inocula digested conclusions from the facts which this mode " L'inoculat of investigation presented for our interpretation.By pus dans le patient experiment and rigorous reasoning, Ricord bien" (p.94 established the truth, which has now been confirmed be regular, throughout Europe from Italy to Norway; namely, is useless to that certain forms of syphilitic sores will produce, facts conce: when inoculated, their like, which in their turn will ceived and s again furnish a secretion capable of being again In the ye inoculated with similar results.It would be difficult cases in wi to overrate the importance of this discovery, so ana-unreservedl, logous to that of the small-pox inoculation.But not been a practical men have, nevertheless, been unable to see inoculation. in the experiments in question a conclusive repre-hospital, ca sentation of that which they daily observe in practice.which the s