tbuckley/cabot-search huggingface dataset:
Amyloid ? peptides mediate physiological remodelling of the acute O sensitivity of adrenomedullary chromaffin cells following chronic hypoxia
Authors: S BROWN, R JOHNSON, R SENARATNE, I FEARON
Journal: Cardiovascular Research (2004)

Objective: The non-neurogenic response of the neonatal adrenal medulla is vital in cardiovascular and respiratory development and to the survival of newborns exposed to hypoxic stress. Here, we examined the acute hypoxic response of immortalised rat adrenomedullary chromaffin cells following exposure to chronic hypoxia (CH; 6% O2 for 24 h). Methods: Ca2+ and K+ channel currents were recorded using by whole-cell patch-clamp. Results: Following incubation in CH, the acute O2 sensitivity of K+ current in immortalised adrenomedullary chromaffin (MAH) cells was enhanced due to a selective increase in the density of an O2-sensitive Ca2+-dependent K+ current, secondary to ROS-mediated augmentation of voltage-gated Ca2+ currents. The effect of CH on Ca2+ currents was not additive to exogenous Aβ1–40 and was blocked by the γ-secretase inhibitors γ-X and γ-VI, demonstrating a role for amyloid β peptide (AβP) production. Ca2+ current enhancement was abolished in the presence of the transcription inhibitor actinomycin D but unaffected by the vacuolar H+ ATPase inhibitor bafilomycin A1. Conclusion: AβP production and transcriptional regulation during CH regulated the properties of a peripheral chemosensory cell, defining a role for these enigmatic peptides in the signalling pathway of a physiological response to CH in the developing cardiovascular system.
Sterol transporter adenosine triphosphate-binding cassette transporter G8, gallstones, and biliary cancer in 62,000 individuals from the general population
Authors: Stefan Stender, Ruth Frikke-Schmidt, Børge G. Nordestgaard, Anne Tybjaerg-Hansen
Journal: Hepatology (2010)

Gallstone disease, a risk factor for biliary cancer, has a strong heritable component, but the underlying genes are largely unknown. To test the hypothesis that ABCG8 (adenosine triphosphate-binding cassette transporter G8) Asp19His (D19H) genotype predicted risk of gallstones and biliary cancer in the general population, we studied 62,279 white individuals from The Copenhagen City Heart Study and The Copenhagen General Population Study, randomly selected to reflect the adult Danish population aged 20 to 80+ years. Endpoints were recorded from January 1976 through May 2009. During a mean follow-up of, respectively, 31 and 4.4 years, 3124 participants developed symptomatic gallstone disease and 30 developed biliary cancer. The multifactorially adjusted hazard ratio for symptomatic gallstone disease was 1.9 (95% confidence interval, 1.7-2.1) in DH heterozygotes (prevalence, 12%), and 3.3 (2.3-4.6) in HH homozygotes (0.4%) versus noncarriers (P for trend <0.001). Mean age at onset of symptomatic gallstone disease was 56 years for noncarriers, 54 for DH heterozygotes, and 52 for HH homozygotes (P for trend <0.001). The fraction of all gallstones attributed to D19H was 11%. The multifactorially adjusted hazard ratio for biliary cancer was 4.0 (1.9-8.4) in DH heterozygotes and HH homozygotes combined versus noncarriers (P < 0.001). The fraction of all biliary cancers attributed to the D19H genotype was 27%. Finally, D19H genotype associated with stepwise increases in plasma levels of alanine aminotransferase and gamma glutamyltransferase of up to 14% and 25% in HH homozygotes, and with corresponding stepwise reductions in plasma levels of total and low-density lipoprotein cholesterol of up to 5% versus noncarriers (all comparisons, P for trend <0.001).In this general population cohort, ABCG8 D19H genotype was an important predictor of both symptomatic gallstone disease and biliary cancer.
State Aid for Private Medical Schools.
Authors: E. Fletcher Ingals
Journal: JAMA (1907)

Chicago, May 11, 1907. <h3>To the Editor:</h3> —The editorial on "The Future of Medical Education in the United States," inThe Journal, May 11, 1907, is timely and covers the field, excepting that it does not suggest a remedy. In this country are between $15,000,000 and $20,000,000 of private capital invested in the various medical schools, and it is not fair that the owners of these schools should be taxed to support state schools, however desirable the latter might be. It is not fair, either, for states to come in competition with this capital. There can be no question that the states should establish standards which will give us as good physicians as there are anywhere in the world. As suggested in your editorial, there is no longer any necessity for turning out a lot of physicians to meet the wants of poor people in thinly settled communities. As it
STUDIES ON A CERTAIN SPREADING FACTOR EXISTING IN BACTERIA AND ITS SIGNIFICANCE FOR BACTERIAL INVASIVENESS
Authors: F. Duran-Reynals
Journal: The Journal of Experimental Medicine (1933)

Invasive strains of staphylococcus and streptococcus contain a soluble factor which markedly increases tissue permeability and enhances the infections produced by these organisms, by other bacteria, and by vaccine virus as well. The non-invasive strains of the same species of staphylococci and streptococci do not contain this factor. The enhancing substance elaborated locally by organisms passes into the circulating blood and bringing about a general increase of tissue permeability may act to enhance local infections elsewhere. The factor is similar in the phenomena it elicits to the spreading factor extracted from many animal tissues, especially from testicle.
Effects of valsartan on left ventricular ejection fraction and diastolic diameter in patients with heart failure: Val-HeFT echocardiographic study
Authors: Mavlene Wong, Lidia Staszewsky, Roberto Latini, Yann-Tong Chiang, Alberto Volpi, Christer Hoglund, Jay N. Cohn
Journal: Journal of the American College of Cardiology (2002)
Simultaneous occurrence of paroxysmal nocturnal hemoglobinuria and chronic lymphocytic leukemia
Authors: Sambit K. Mohanty, Neelam Varma, Pankaj Malhotra, Subhash Varma, Harpreet Vohra, Gurjeevan Garewal
Journal: American Journal of Hematology (2004)

To the Editor: Neurotoxicity is a well-recognized complication following high-dose cytosine arabinoside (HIDAC).The pathophysiology of this toxicity is unknown, although an immune-mediated mechanism is hypothesized.We describe a patient with AML who suffered both cerebellar toxicity and peripheral neuropathy following high-dose cytarabine and showed excellent response to methylprednisolone.A 40-year-old married woman was diagnosed with acute myeloid leukemia, FAB-M2, in August 2002.She received standard induction chemotherapy with cytarabine and daunorubicin in 7-day and 3-day regimens, respectively.Her bone marrow on day 21 showed marrow to be in remission.She was given consolidation chemotherapy in the form of HIDAC in the dose of 3 g/m 2 twice daily.She developed high-grade fever on day 3, and the last dose of HIDAC was withheld.She received a total of 22.5 g of cytarabine.On day 7, she developed slurring of speech followed by gait ataxia, diplopia, dysmetria, and dysdiadochokinesia.Brain MRI on day 10 showed early cerebellar atrophy.On day 35, she noted increased weakness and paresthesias of upper and lower limbs but without an increase in uncoordination.She had proximal muscle weakness of both upper and lower limbs, absent deep tendon reflexes along with impaired joint position, and light touch sensation in a glove-and-stocking pattern.Her nerve conduction study was suggestive of distal symmetrical sensorimotor largefiber polyneuropathy.A sural nerve biopsy was nondiagnostic.Cerebrospinal fluid analysis showed no cells, proteins 45 mg (40-75 mg), sugar 54 mg (corresponding blood sugar 78 mg).She was administered methyl prednisolone 1 g IV each day for 3 days followed by oral steroids (1 mg/kg).After about 6 days, she started showing improvement in her power.She continued to improve gradually.Her power in the lower and upper limbs along with cerebellar functions improved by more than 90% over next 3-4 weeks.She was able to walk independently with no uncoordination.She refused any further chemotherapy, relapsed 3 months later, and died.The present case describes a patient with AML who had both cerebellar toxicity and peripheral neuropathy, thus implicating HIDAC as the causative agent [1][2][3].The cause of peripheral neuropathy has been attributed to
FDG PET/CT Findings of Mesenchymal Hamartoma of the Liver in an Adult
Authors: Masatoyo Nakajo, Seishi Jinnouchi, Nobuo Hamada, Kazunobu Sueyoshi, Sumika Matukita, Hiroaki Tanabe, Rie Tateno, Masayuki Nakajo
Journal: Clinical Nuclear Medicine (2009)

We report a case of a 38-year-old man with a mesenchymal hamartoma of the liver (MHL) in which FDG did not accumulate intensely. The MHL was an ill-defined multicystic tumor on computed tomography and magnetic resonance imaging. It was an ill-defined mass with multihypometabolic areas on FDG PET/CT. When an ill-defined liver mass with multihypometabolic areas is observed on FDG PET/CT, MHL should be included in the differential diagnosis of liver tumors.
Macrophage expression of active MMP-9 induces acute plaque disruption in apoE-deficient mice
Authors: Peter J. Gough, Ivan G. Gomez, Paul T. Wille, Elaine W. Raines
Journal: Journal of Clinical Investigation (2005)

The majority of acute clinical manifestations of atherosclerosis are due to the physical rupture of advanced atherosclerotic plaques. It has been hypothesized that macrophages play a key role in inducing plaque rupture by secreting proteases that destroy the extracellular matrix that provides physical strength to the fibrous cap. Despite reports detailing the expression of multiple proteases by macrophages in rupture-prone regions, there is no direct proof that macrophage-mediated matrix degradation can induce plaque rupture. We aimed to test this hypothesis by retrovirally overexpressing the candidate enzyme MMP-9 in macrophages of advanced atherosclerotic lesions of apoE–/– mice. Despite a greater than 10-fold increase in the expression of MMP-9 by macrophages, there was only a minor increase in the incidence of plaque fissuring. Subsequent analysis revealed that macrophages secrete MMP-9 predominantly as a proform, and this form is unable to degrade the matrix component elastin. Expression of an autoactivating form of MMP-9 in macrophages in vitro greatly enhances elastin degradation and induces significant plaque disruption when overexpressed by macrophages in advanced atherosclerotic lesions of apoE–/– mice in vivo. These data show that enhanced macrophage proteolytic activity can induce acute plaque disruption and highlight MMP-9 as a potential therapeutic target for stabilizing rupture-prone plaques.
DIAGNOSIS OF URETERAL AND RENAL DISEASES IN WOMEN.
Authors: HOWARD A. KELLY
Journal: JAMA (1895)

It is my purpose in this paper to consider in outline the new methods of ureteral examination in women which I have developed recently. I shall therefore pass over those important diagnostic points which are already well recognized, such as clinical history, urinalysis, and ureteral and renal palpation. My method lays stress upon three steps in the investigation, namely: Inspection. Catheterization of the ureter. Catheterization of the pelvis of the kidney. It will be observed that each of these procedures gives direct and positive information in marked contrast to the inferential methods of diagnosis of ureteral affections hitherto deemed sufficient. <h3>I.—INSPECTION.</h3> Inspection is limited to the orifices of the ureters and notes: 1, the appearance of the orifice and its immediate surroundings; 2, the character of the fluid discharged from the orifice; and 3, the character of the flow, whether absent, intermittent, or continuous. Inspection is accomplished by placing the
Prediction of 30-Day Mortality Among Patients With Thrombolysis-Related Intracranial Hemorrhage
Authors: Michael A. Sloan, Cathy A. Sila, Kenneth W. Mahaffey, Christopher B. Granger, W. T. Longstreth, Peter Koudstaal, Harvey D. White, Joel M. Gore, Maarten L. Simoons, W. Douglas Weaver, Cindy L. Green, Eric J. Topol, Robert M. Califf
Journal: Circulation (1998)

Background —Limited information exists on risk factors for mortality after thrombolysis-related intracranial hemorrhage. We wished to determine the characteristics associated with 30-day mortality after thrombolysis-related intracranial hemorrhage. Methods and Results —We performed an observational analysis within a randomized trial of 4 thrombolytic therapies, conducted in 1081 hospitals in 15 countries. Patients presented with ST-segment elevation within 6 hours of symptom onset. Our population was composed of the 268 patients who had primary intracranial hemorrhage after thrombolysis. With univariable and multivariable analyses, we identified clinical and brain imaging characteristics that would predict 30-day mortality among these patients. CT or MRI were available for 240 patients (90%). The 30-day mortality rate was 59.7%. Glasgow Coma Scale score, age, time from thrombolysis to symptoms of intracranial hemorrhage, hydrocephalus, herniation, mass effect, intraventricular extension, and volume and location of intracranial hemorrhage were significant univariable predictors. Multivariable analysis of 170 patients with complete data, 98 of whom died, identified the following independent, significant predictors: Glasgow Coma Scale score (χ 2 , 19.3; P &lt;0.001), time from thrombolysis to intracranial hemorrhage (χ 2 , 15.8; P &lt;0.001), volume of intracranial hemorrhage (χ 2 , 11.6; P &lt;0.001), and baseline clinical predictors of mortality in the overall GUSTO-I trial (χ 2 , 10.3; P =0.001). The final model had a C-index of 0.931. Conclusions —This model provides excellent discrimination between patients who are likely to live and those who are likely to die after thrombolytic-related intracranial hemorrhage; this may aid in making decisions about the appropriate level of care for such patients.
Advanced glycation end product (AGE)-immunoreactive materials in chronic prurigo patients receiving a long-standing haemodialysis
Authors: N. Fujimoto, S. Tajima
Journal: British Journal of Dermatology (2004)

We report two patients with chronic prurigo who suffered from chronic renal failure and were treated by haemodialysis. Histological examination of pruritic nodules revealed that the papillary dermis of the lesional skin was eosinophilic and amorphous, and free from dermal cell infiltration. Immunohistochemical study demonstrated that advanced glycation end product (AGE)-immunoreactive materials accumulated in the papillary dermis of the lesional skin. This immunohistochemical finding was never observed in the nonlesional skin adjacent to prurigo nodules of the present cases, and renal disease-free prurigo skin (n = 6) and nonprurigo skin of haemodialysis patients (n = 3). AGE-modified materials in the papillary dermis may be related to the pathogenesis of prurigo nodules in the haemodialysis patients.
Government issues guidelines to stem rising tuberculosis rates in prisons
Authors: A. Skolnick
Journal: JAMA (1989)

IN RESPONSE to the alarming increase of tuberculosis (TB) rates in many of the nation's prisons, the Centers for Disease Control (CDC), Atlanta, Ga, has published recommendations for the prevention and control of TB among prison populations (<i>MMWR</i>. 1989;38:313-320,325 and this issue.) This is the first time the CDC has issued guidelines regarding health care in correctional institutions. Speaking at the 13th National Conference on Correctional Health Care in Chicago, Ill, John J. Seggerson, Jr, MD, chief, Program Services Branch of the CDC's Division of Tuberculosis Control, explained the epidemiologic reasons for the recommendations. <h3>Eleven Known Outbreaks</h3> Over the last few years, increasing rates of TB in certain demographic pockets have brought the decline in the incidence of TB in the United States to a halt. Since 1985, 11 known TB outbreaks have occurred in prisons in eight states, Seggerson says. One such outbreak was described at the conference by
Government gives details of quality drive in the NHS in England
Authors: J. Warden
Journal: BMJ (1998)

Details of two new quangos to be superimposed on the NHS in England--one to set clinical standards, the other to enforce them--are given in a government green paper, A First Class Service: Quality in the New NHS , issued last week for consultation.

With the promise of more money in the pipeline, the government is setting conditions in terms of supervising professional standards and restoring its own and the public's confidence after recent, well publicised clinical failures. The tone is one of collaboration, but with an element of compulsion and the threat of stronger measures.

The green paper is epitomised by ministerial enthusiasm for a new post of director of health improvement. The director is intended to be a high profile inspector general of the NHS conducting spot checks and with the power to act against failing hospitals or individual doctors. The proposals are in line with last December's white paper, The New NHS ( BMJ 1997;315:1561), but they acquire fresh impact in the aftermath of the recent paediatric surgery scandal in …
Aberrant expression of p53 tumour-suppressor protein in non-melanoma skin cancer
Authors: J.M. McGREGOR, C.C-W. YU, E.A. DUBLIN, D.A. LEVISON, D.M. MacDONALD
Journal: British Journal of Dermatology (1992)

Expression of the cellular p53 tumour-suppressor protein was examined in 78 epidermal tumours, including basal and squamous cell carcinomas, keratoacanthomas, solar keratoses, Bowen's disease and viral warts. An immunohistochemical study was employed using the antibody CM-1, raised against recombinant human p53 protein. Positive staining for p53, not detectable in normal cells because wild-type p53 is rapidly degraded, reflects abnormal stabilization of p53 protein, and in many cases suggests p53 gene mutation. p53 immunoreactivity was not observed in normal skin or in viral warts. In contrast, positive staining for CM-1 was seen throughout the tumour in the majority of basal and squamous cell carcinomas and in Bowen's disease. Immunoreactivity to p53 was also observed in the majority of keratoacanthomas and solar keratoses, but was confirmed to areas of dysplastic basal epithelium. This study demonstrates that accumulation of p53 protein, suggestive in many cases of p53 gene mutation and hence loss of tumour-suppressor function, may occur as an important early step in the development of diverse epidermal cancers.
Significance of Endoscopy for Evaluation of Vesico-ureteral Reflux
Authors: R. Ackermann
Journal: Endoscopy (1979)

The role of urethrocystoscopy in the evaluation of vesico-ureteral reflux is discussed. In addition to voiding cystourethrograms and excretory urography endoscopic examination of patients with vesico-ureteral reflux permits the determination of the extent of the uretero-vesical junction malformation. The length of the submucosal ureter, the orifice configuration and its location as well as the trigonal muscular development are parameters which lend themselves to endoscopic evaluation. Their importance in the decision of whether vesico-ureteral reflux is treated conservatively or surgically is discussed. In addition, urethrocystoscopy may give valuable information on the causes of secondary vesico-ureteral reflux.
Tobacco Smoking and the Humanities
Authors: Alvan L. Barach
Journal: JAMA (1970)

<h3>To the Editor.—</h3> The voice of the American Cancer Society on NBC indicated that cigarette smoking was a cause of pulmonary emphysema; the warning continued, "emphysema eventually causes suffocation" (Jan 31, 1970). Patients with respiratory disease have been frightened by pronouncements of this nature, whether they smoke or not. Is this kind of menacing propaganda justified on television? According to Jacques Barzun, Already the citizen is assailed with pictures and slogans about crippling and killing ailments, but this is apparentlly not enough. And the point here is not whether lives can and should be saved. It is whether the fear and duty inculcated by the propaganda are consistent with a tolerable life. When British Television broadcast medical and surgical programs, suicides followed. This is not complete evidence, but it is a sign that perhaps we have reached a peak of admonition beyond which it is not sane to go. No
The Discovery Rule in Malpractice Cases
Authors: William J. Curran
Journal: New England Journal of Medicine (1969)

ONE of the most important medical-malpractice cases of 1969 is the decision of the nationally influential Court of Appeals of New York in Flanagan v. Mt. Eden Gen. Hospital. 1 In this case, a closely split court (4:3) overruled 39 years of firmly established precedent and changed the interpretation of the State's medical-malpractice statute of limitations first enacted in 1900.In the Flanagan case the plaintiff had been operated on in June, 1958, for removal of the gallbladder. The operation was successful, and she was discharged from care by the surgeon in due course. In the spring of 1966, she experienced . . .
Central control of bone remodeling by neuromedin U
Authors: Shingo Sato, Reiko Hanada, Ayako Kimura, Tomomi Abe, Takahiro Matsumoto, Makiko Iwasaki, Hiroyuki Inose, Takanori Ida, Michihiro Mieda, Yasuhiro Takeuchi, Seiji Fukumoto, Toshiro Fujita, Shigeaki Kato, Kenji Kangawa, Masayasu Kojima, Ken-ichi Shinomiya, Shu Takeda
Journal: Nature Medicine (2007)
Transforming growth factor β can mediate apoptosis via the expression of TRAIL in human hepatoma cells
Authors: Kerstin Herzer, Tom M. Ganten, Henning Schulze-Bergkamen, Anne Grosse-Wilde, Ronald Koschny, Peter H. Krammer, Henning Walczak
Journal: Hepatology (2005)

Abstract Transforming growth factor β (TGF-β) has been shown to induce apoptotic cell death in normal and transformed hepatocytes. However, the exact mechanism through which TGF-β induces cell death is still unknown. We examined a potential role of various death receptor/ligand systems in TGF-β–induced apoptosis and identified the tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) as a mediator of TGF-β–induced apoptosis in hepatoma cells. TGF-β–induced apoptosis is significantly impaired upon blockage of TRAIL. We show that TRAIL is upregulated in hepatoma cells upon treatment with TGF-β, whereas TRAIL receptor levels remain unchanged. In conclusion , our results provide evidence that the TRAIL system is critically involved in TGF-β–induced cell death in liver pathology. (Hepatology 2005;42:183–192.)