tbuckley/cabot-search huggingface dataset:
Effect of pirfenidone on rat hepatic stellate cell proliferation and collagen production
Authors: Antonio Di Sario, Emanuele Bendia, Gianluca Svegliati Baroni, Francesco Ridolfi, Alessandro Casini, Elisabetta Ceni, Stefania Saccomanno, Marco Marzioni, Luciano Trozzi, Paola Sterpetti, Silvia Taffetani, Antonio Benedetti
Journal: Journal of Hepatology (2002)
Predominance of the Curative Model of Medical Care
Authors: Ellen Fox
Journal: JAMA (1997)

Despite a multitude of efforts in recent years to reform medical education, and despite the significant gains that have been achieved, some refractory problems remain. Two articles in this issue of The Journal describe persistent shortcomings in the present medical education system. Billings and Block<sup>1</sup>summarize the results of an extensive literature review of end-of-life education in medical schools, concluding that the training currently provided inadequately prepares students to care for dying patients. Christakis and Feudtner<sup>2</sup>describe anecdotal experiences of medical students and residents on inpatient services, illustrating how the transitory and time-pressured nature of that environment can have disturbing effects on trainees' ethical development. On the face of it, these two articles may seem to have little in common. On a deeper level, however, these articles share a common theme: Both can be construed as serious critiques of medical education's prevailing overemphasis on a curative model of
Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans
Authors: Supriya Srinivasan, Cecile Lubrano-Berthelier, Cedric Govaerts, Franck Picard, Pamela Santiago, Bruce R. Conklin, Christian Vaisse
Journal: Journal of Clinical Investigation (2004)

The melanocortin-4 receptor (MC4R), a centrally expressed G protein–coupled receptor (GPCR), is essential for the maintenance of long-term energy balance in humans. Mutations in MC4R are the most common genetic cause of obesity. Since activation of this receptor leads to a decrease in food intake, MC4R is also a major therapeutic target for the treatment of obesity. Control of MC4R activity in vivo is modulated by the opposing effects of the anorexigenic agonist α–melanocyte-stimulating hormone (α-MSH) and the orexigenic antagonist agouti-related protein (AGRP). In addition, experiments in vitro have demonstrated that the human MC4R has an intrinsic constitutive activity on which AGRP also acts as an inverse agonist. The physiological role of this constitutive activity in the control of energy balance as well as the domain of the protein implicated in its maintenance are unknown. By systematically studying functional defects in naturally occurring MC4R mutations from obese patients, we defined a cluster of N-terminal mutations that selectively impair the constitutive activity of the receptor. Further characterization of this domain demonstrated that it functions as a tethered intramolecular ligand that maintains the constitutive activity of MC4R and may provide novel avenues for the design of drugs targeting this receptor. Our results also suggest that the tonic satiety signal provided by the constitutive activity of MC4R may be required for maintaining long-term energy homeostasis in humans.
640 IN VIVO LIVER ENDOPLASMIC RETICULUM STRESS IN CHRONIC HEPATITIS C
Authors: T. Asselah, I. Bièche, A. Mansouri, I. Laurendeau, D. Cazals-Hatem, G. Feldmann, P. Bedossa, V. Paradis, M. Martinot-Peignoux, D. Lebrec, C. Guichard, E. Ogier-Denis, M. Vidaud, Z. Tellie, V. Soumelis, P. Marcellin, R. Moreau
Journal: Journal of Hepatology (2010)
Changing the Cell Source in Cell Therapy?
Authors: Graziella Pellegrini
Journal: New England Journal of Medicine (2004)

One dream of scientists is to be able to rebuild, in vitro, "spare parts" to replace injured or diseased tissues — a notion that was once relegated to the realm of science fiction. The concept that stem cells that are ostensibly site-specific can give rise to (and maintain) mature tissues has made adult stem cells the focus of intense research designed to explore their promise for the treatment of a variety of human diseases.Adult stem cells are defined as clonogenic, self-renewing progenitor cells that can generate one or more specialized types of cells. However, major obstacles in this field . . .
GROWING TUBERCLE BACILLI
Authors: H. J. CORPER
Journal: JAMA (1933)

An acquaintance with the propagation of tubercle bacilli is the basis for conceptions regarding the pathogenesis of tuberculosis, and this can be expressed simply as the interaction of two components: the one, the tubercle bacillus—the offender—in its ability to persist and to develop in the animal body, and the other component—the host—the cells and fluids of the body which serve to harbor or nourish these bacilli to the point of offensiveness and destructiveness. The paradoxical nature of the pathogenic reactions of tubercle bacilli in different animal species leaves a great deal to be desired in the way of adequate explanation for the present, but suggests the taking of an inventory and revaluation of some of the experiences accumulated during the past few decades, especially concerning the growth and nature of tubercle bacilli under controlled conditions in the culture receptacle. The fundamental investigations recently concerned with growing tubercle bacilli have resolved
Vitamin E (?-tocopherol) does not inhibit platelet stimulation by oxidized low density lipoprotein in vitro
Authors: T. Szuwart, R.B. Dierichs, B. Zhao
Journal: American Journal of Hematology (1999)

Platelet-rich plasma were treated with increasing concentrations of vitamin E (alpha-tocopherol). Washed platelets were exposed to oxidized low density lipoprotein (LDL) and examined by aggregometry and electron microscopy. The treatment of washed platelets by oxidized LDL induced morphological signs of activation like pseudopodia formation and an increase in light transmission. Alpha-tocopherol in a range of 0.001-1.0 mmol had no inhibiting influences on platelet activation by oxidized LDL. These results indicate that the free radical scavenger vitamin E cannot directly inhibit platelet activation by oxidized LDL. It may be supposed that platelet activation by oxidized LDL does not occur in a radical-dependent mechanism.
Requesting Consent for an Invasive Procedure in Newly Deceased Adults
Authors: Robert M. McNamara
Journal: JAMA (1995)

<h3>Objective.</h3> —Ethical concerns exist over the performance of medical procedures, such as endotracheal intubation, on newly deceased patients without family consent. This study examined the process of obtaining consent for the purpose of performing an invasive procedure in newly deceased adults. <h3>Design.</h3> —A prospective case series. <h3>Participants.</h3> —The families of patients who died during a 5-month period were requested to provide consent to perform wire-guided retrograde tracheal intubation. <h3>Main Outcome Measures.</h3> —Differences between success and failure in obtaining consent including information on the deceased, family reasons for their decision, and the experience of those requesting consent. <h3>Results.</h3> —Consent was requested from 44 families and 26 (59%) agreed to the procedure. This success rate was achieved despite the lack of a prior relationship with the family by the persons requesting consent. Consent was obtained more frequently in unexpected than expected deaths (77% vs 41%,<i>P</i>=.03). There were no differences in success rates for consent for age, race, sex, or do-not-resuscitate status of the deceased. Spouses consented more frequently than children (77% vs 50%,<i>P</i>=.25). The two physicians reported greater comfort in requesting consent than the nurse anesthetist investigator. In one instance, the consent process may have increased the emotional distress of the family. <h3>Conclusion.</h3> —Consent can frequently be obtained from families for an invasive procedure in newly deceased adults. Physicians should reconsider the practice of performing postmortem procedures without obtaining family consent. (<i>JAMA</i>. 1995;273:310-312)
Book Review Dynamic Psychotherapy: An introductory approach By Marc H. Hollender and Charles V. Ford. 229 pp. Washington, D.C., American Psychiatric Press, 1990. $$31. psychodynamic psychiatry in clinical Practice By Glen O. Gabbard. 505 pp. Washington, D.C., American Psychiatric Press, 1990. $$49.95.
Authors: Renée L. Gelman
Journal: New England Journal of Medicine (1991)
Common genetic variants in the chromogranin A promoter alter autonomic activity and blood pressure
Authors: Y. Chen, F. Rao, J.L. Rodriguez-Flores, N.R. Mahapatra, M. Mahata, G. Wen, R.M. Salem, P.-A.B. Shih, M. Das, N.J. Schork, M.G. Ziegler, B.A. Hamilton, S.K. Mahata, D.T. O'Connor
Journal: Kidney International (2008)
Cannabinoid CB1 receptor expression in relation to visceral adipose depots, endocannabinoid levels, microvascular damage, and the presence of the Cnr1 A3813G variant in humans
Authors: Marica Bordicchia, Ilaria Battistoni, Lucia Mancinelli, Elena Giannini, Giada Refi, Daniele Minardi, Giovanni Muzzonigro, Roberta Mazzucchelli, Rodolfo Montironi, Fabiana Piscitelli, Stefania Petrosino, Paolo Dessì-Fulgheri, Alessandro Rappelli, Vincenzo Di Marzo, Riccardo Sarzani
Journal: Metabolism (2009)
Comparative transcriptional and functional profiling defines conserved programs of intestinal DC differentiation in humans and mice
Authors: Payal B Watchmaker, Katharina Lahl, Mike Lee, Dirk Baumjohann, John Morton, Sun Jung Kim, Ruizhu Zeng, Alexander Dent, K Mark Ansel, Betty Diamond, Husein Hadeiba, Eugene C Butcher
Journal: Nature Immunology (2013)
Sudden Reversible Osmotic Lens Damage (“Sugar Cracks”) after Initiation of Metformin
Authors: Gijsbrecht J.M. Tangelder, Michiel Dubbelman, Peter J. Ringens
Journal: New England Journal of Medicine (2005)

To the Editor: We observed a unique type of ocular lens damage in a 62-year-old man with no history of ophthalmologic disease. He had a history of heart failure requiring five-vessel cardiac bypass surgery. He had polydipsia and polyuria, which became markedly aggravated after an overseas trip; on the patient's return, his primary care physician diagnosed diabetes mellitus (serum glucose level, 21.8 mmol per liter [393 mg per deciliter]; glycosylated hemoglobin level, 17.5 percent). Metformin (at a dose of 750 mg twice daily) reduced the serum glucose level to 14.6 mmol per liter (263 mg per deciliter) within four days . . .
A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease.
Authors: H Klima, K Ullrich, C Aslanidis, P Fehringer, K J Lackner, G Schmitz
Journal: Journal of Clinical Investigation (1993)

The genetic defect leading to cholesteryl ester storage disease (CESD) has been determined in a 12-yr-old patient. Lysosomal acid lipase (LAL) activity in cultured skin fibroblasts was reduced to approximately 9% of control fibroblasts. Plasma cholesterol (255 mg/dl) and LDL-cholesterol (215 mg/dl) were elevated whereas HDL-cholesterol was reduced (19 mg/dl). Triglycerides were moderately elevated (141 mg/dl). There were no clinical abnormalities with the exception of hepatosplenomegaly. Both parents have reduced LAL activity in white blood cells. PCR analysis of the LAL mRNA from the propositus revealed a single slightly smaller mRNA species in skin fibroblasts as well as in leukocytes. The mother of the patient and his older brother had two mRNA species: one of normal size and one of the same size as the propositus. The father has a LAL mRNA of normal size only. Sequence analysis of a PCR-amplified cDNA fragment showed a 72-bp in-frame deletion resulting in the loss of the codons for amino acids 254-277. Analysis of genomic DNA revealed that the 72 bp represent an exon, indicating that the deletion in the mRNA is caused by defective splicing. Sequence analysis of the patient's genomic DNA revealed a G-->A substitution in the last nucleotide of the 72-bp exon in one of his alleles. The mutant allele was shown to cosegregate with the truncated mRNA in the pedigree, providing further evidence that the G-->A substitution causes aberrant splicing and exon skipping. No normal-sized mRNA is detectable in the propositus even though he is not homozygous for the splice site mutation. This can be only accounted for by assuming that he is a compound heterozygote with a null allele inherited from his father. In summary, the data presented provide evidence that deletion of the codons for amino acids 254-277 in the LAL mRNA in combination with a null allele cause the clinical expression of CESD in our patient.
Selective Antegrade Cerebral Perfusion Attenuates Brain Metabolic Deficit in Aortic Arch Surgery
Authors: D.K. Harrington, A.S. Walker, H. Kaukuntla, R.M. Bracewell, T.H. Clutton-Brock, M. Faroqui, D. Pagano, R.S. Bonser
Journal: Circulation (2004)

Aortic arch surgery has a high incidence of brain injury. This may in part be caused by a cerebral metabolic deficit observed after hypothermic circulatory arrest (HCA). We hypothesized that selective antegrade cerebral perfusion (SACP) would attenuate this phenomenon.In a prospective randomized trial, 42 adult patients were allocated to either HCA (22) or SACP. HCA occurred at a nasopharyngeal temperature of 15 degrees C and SACP at a corporeal temperature of 25 degrees C with cerebral perfusion at 15 degrees C. Paired arterial and jugular venous samples were taken before and after arrest. Continuous transcranial Doppler monitoring of middle cerebral artery velocity (MCAV) was performed. Neuropsychometric testing was performed preoperatively and at 6 and 12 weeks postoperatively. There were 3 hospital deaths (7.1%), 2 strokes (4.8%), and 6 episodes of transient neurological deficit (14.3%). From before to after arrest, jugular bulb pO2 changed by -21.67 mm Hg (26.4) in the HCA group versus +2.27 mm Hg (18.8) in the SACP group (P=0.007). Oxygen extraction changed by +1.7 mL/dL (1.3) in the HCA group versus -1 mL/dL (2.4) in the SACP group (P<0.001). MCAV increased by 6.25 cm/s (9.1) in the HCA group and 19.2 cm/s (10.1) in the SACP group (P=0.001). Incidence of neuropsychometric deficit at 6 weeks was 6/12 (50%) in HCA patients and 8/10 (80%) in SACP patients (P=0.2), and at 12 weeks was 6/16 (38%) in HCA patients and 4/11 (36%) in SACP patients (P=1).SACP attenuates the metabolic changes seen after HCA. Further studies are required to assess optimal perfusion conditions and clinical outcome.
Evaluation of Myocardial Ischemia After Surgical Repair of Anomalous Aortic Origin of a Coronary Artery in a Series of Pediatric Patients
Authors: Julie A. Brothers, Michael G. McBride, Mohamed A. Seliem, Bradley S. Marino, Ryan S. Tomlinson, Miguel H. Pampaloni, J. William Gaynor, Thomas L. Spray, Stephen M. Paridon
Journal: Journal of the American College of Cardiology (2007)
Elevated Methylmalonic Acid and Total Homocysteine Levels Show High Prevalence of Vitamin B_12 Deficiency after Gastric Surgery
Authors: Anne E. Sumner
Journal: Annals of Internal Medicine (1996)

Objective: To determine the prevalence of vitamin B12 deficiency in patients who have had gastric surgery. Design: Cross-sectional study. Setting: Philadelphia Veterans Affairs Medical Center. Participants: 61 patients who had had gastric surgery and 107 controls. Measurements: Serum levels of vitamin B12, folate, methylmalonic acid, and total homocysteine measured before and after treatment in participants with vitamin B12 deficiency. Vitamin B12 deficiency was defined as one of the following: 1) a serum vitamin B12 level less than 221 pmol/L and an elevated methylmalonic acid level; 2) a serum vitamin B12 level less than 221 pmol/L and an elevated total homocysteine level that decreased with vitamin B12 treatment; or 3) in patients unavailable for treatment, a serum vitamin B12 level less than 221 pmol/L, a folate level greater than 9 nmol/L, and an elevated total homocysteine level. Results: Study patients and controls were similar in age, sex, and racial distribution. Nineteen patients (31%) and 2 controls (2%) had vitamin B12 deficiency (P < 0.001). Twelve (63%) of the 19 vitamin B12-deficient patients had elevated total homocysteine levels. In all participants with vitamin B12 deficiency who received treatment (15 of 21), methylmalonic acid and total homocysteine levels decreased substantially, confirming the deficiency before treatment. Conclusion: Patients who have had gastric surgery have a high prevalence of vitamin B12 deficiency. Prompt recognition and treatment of the deficiency with resultant normalization of elevated total homocysteine and methylmalonic acid levels may prevent the development of cardiovascular, hematologic, and neurologic abnormalities. Our data support both frequent screening and vitamin B12 replacement therapy in patients who have had gastric surgery and have serum vitamin B12 levels less than 221 pmol/L.
TRIB3 alters endoplasmic reticulum stress-induced β-cell apoptosis via the NF-κB pathway
Authors: Ni Fang, Wenjian Zhang, Shiqing Xu, Hua Lin, Zai Wang, Honglin Liu, Qing Fang, Chenghui Li, Liang Peng, Jinning Lou
Journal: Metabolism (2014)
THE DENTIST IN THE UNITED STATES NAVY.
Authors: RICHARD GRADY
Journal: JAMA (1907)

The title of this paper is ambitious but not correct. In the Navy there is no such grade as dentist, as there is no authority of law under which such an appointment can be made, except for service at the United States Naval Academy. The need of dental services in the Army and Navy was first urged fully fifty years ago. The matter had been laid before Congress several times previous to the Spanish-American War, but without any action being taken. A dentist was appointed at the U. S. Naval Academy with the rank of assistant surgeon, and that was all that had been done in the matter, except that at the opening of the Civil War all army surgeons were supplied with forceps. It is difficult to state with precision at whose suggestion the initial steps were taken which culminated in legislation creating a dental corps in connection with
Effect of luminal and peritubular HCO3(-) concentrations and PCO2 on HCO3(-) reabsorption in rabbit proximal convoluted tubules perfused in vitro.
Authors: S Sasaki, C A Berry, F C Rector
Journal: Journal of Clinical Investigation (1982)

The effect of luminal and peritubular HCO3(-) concentrations and PCO2 on HCO3(-) reabsorption was examined in rabbit proximal convoluted tubules perfused in vitro. Increasing luminal HCO3(-) concentration from 25 to 40 mM without changing either peritubular HCO3(-) concentration or PCO2, stimulated HCO3(-) reabsorption by 41%. When luminal HCO3(-) concentration was constant at 40 mM and peritubular HCO3(-) concentration was increased from 25 to 40 mM without changing peritubular PCO2, a 45% reduction in HCO3(-) reabsorption was observed. This inhibitory effect of increasing peritubular HCO3(-) concentration was reversed when peritubular pH was normalized by increasing PCO2. Passive permeability for HCO3(-) was also measured and found to be 1.09 +/- 0.17 X 10(-7) cm2 s-1. Using this value, the passive flux of HCO3(-) could be calculated. Only a small portion (less than 23%) of the observed changes in net HCO3(-) reabsorption can be explained by the passive HCO3(-) flux. We conclude that luminal and peritubular HCO3(-) concentrations after HCO3(-) reabsorption by changing the active H+ secretion rate. Analysis of these data suggest that both luminal and peritubular pH are major determinants of HCO3(-) reabsorption.
Dependency of Cardiac Resynchronization Therapy on Myocardial Viability at the LV Lead Position
Authors: Michael Becker, Christian Zwicker, Markus Kaminski, Andreas Napp, Ertunc Altiok, Christina Ocklenburg, Zvi Friedman, Dan Adam, Patrick Schauerte, Nikolaus Marx, Rainer Hoffmann
Journal: JACC. Cardiovascular imaging (2011)
Families prepare to sue law firm over handling of cases against MMR vaccine manufacturers
Authors: C. Dyer
Journal: BMJ (2011)

Families who claim that their children developed encephalitis from an early type of measles, mumps, and rubella (MMR) vaccine but that their cases were wrongly lumped together with more than 1000 autism cases are preparing to sue the law firm that later merged with the firm that led the group action.

Three families who believe that their children developed encephalitis and permanent damage such as learning difficulties, epilepsy, and deafness after they were given an earlier form of the vaccine say …
What One Internist Does in His Practice
Authors: JOHN F. BURNUM
Journal: Annals of Internal Medicine (1973)

In response to the acute shortage of physicians in primary care, should practitioner internists be trained in shorter programs that stress community practice and become largely primary physicians? A study of one internist's practice concurs with opinion that the excessively busy internist is indeed a primary physician for many of his patients and that the practice of medicine has a special content and philosophy of patient care in which all internists should be versed. But he may also serve as a consultant and often treats patients with the most complex and demanding medical-school-type problems. Train primary physicians we must, whether in modified programs based in internal medicine or otherwise, but the education of the internist proper may well demand the full traditional university hospital experience plus additional training in the practice of medicine, the essential qualities of which have been partly identified in this study of a practice.
THE COSTATOME IN EXCISION OF THE RIB.
Authors: J. F. BALDWIN
Journal: JAMA (1883)

Being called upon recently to excise a portion of a rib, in a critical case of chronic empyema in which closure of the pus cavity, which I had previously freely opened, was prevented by inability of the chest wall to further retract, I took occasion to review the different methods in vogue for the performance of this operation. The incision through the flesh is of course easy; nor is the peeling off of the periosteum difficult, but it is not so easy to cut through the bone and at the same time not injure the soft parts. The chain saw, the Hey saw and the trephine are the means usually employed to cut the bone, the soft parts being held aside meantime by retractors or by a strip of leather, pasteboard or flexible metal passed behind the rib. None of these methods, however, are free from objections, chief among which
A Case of Maturity-Onset Diabetes Mellitus Resistant to Insulin but Responsive to Tolbutamide
Authors: Marc Rendell, Donald Slevin, Gary Meltz, James Simpson, Anthony Barquet
Journal: Annals of Internal Medicine (1979)

A nonobese patient with maturity-onset diabetes mellitus was hospitalized for treatment of an ulcer on his right foot. During this episode, his diabetic control worsened, and he proved unresponsive to exogenous insulin. Unresponsiveness to insulin persisted after healing of the ulcer. Tolbutamide therapy was then begun and produced a marked reduction in blood sugar levels. Withdrawal of the drug was accompanied by a progressive rise in blood sugar level. Intravenous infusion of regular pork insulin at rates of 45 U/h and single-component pork insulin at rates of 120 U/h had minimal effect on the blood sugar level. High levels of antibody to beef insulin were measured, with lower levels of pork insulin antibodies. C-peptide values were in a normal range before tolbutamide treatment and increased after use of the drug.