tbuckley/cabot-search huggingface dataset:
Hypoxia Increases Resistance of Human Pancreatic Cancer Cells to Apoptosis Induced by Gemcitabine
Authors: Kenji Yokoi, Isaiah J. Fidler
Journal: Clinical Cancer Research (2004)

Hypoxia, frequently found in the center of solid tumor, is associated with resistance to chemotherapy by activation of signaling pathways that regulate cell pro-liferation, angiogenesis, and apoptosis. We determined whether hypoxia can increase the resistance of human pancreatic carcinoma cells to gemcitabine-induced apoptosis by activation of phosphatidylinositol 3'-kinase (PI3K)/Akt, MEK/mitogen-activated protein kinase (extracellular signal-regulated kinase) [MAPK(Erk) kinase (MEK)], and nuclear factor kappa B (NF-kappa B) signaling pathways.We evaluated the phosphorylation of Akt and MAPK(Erk), DNA binding activity of NF-kappa B, and apoptosis induced by gemcitabine in L3.6pl human pancreatic cancer cells under normoxic and hypoxic conditions. We then examined the effects of the PI3K inhibitor LY294002, MEK inhibitor U0126, and the epidermal growth factor receptor tyrosine kinase inhibitor PKI 166 on these signaling pathways and induction of apoptosis.Hypoxic conditions increased phosphorylation of Akt and MAPK(Erk) and NF-kappa B DNA binding activity in L3.6pl cells. The activation of Akt and NF-kappa B was prevented by LY294002, whereas the activity of MAPK(Erk), but not NF-kappa B, was inhibited by U0126. The increased activation of Akt, NF-kappa B, and MAPK(Erk) was inhibited by PKI 166. Under hypoxic conditions, L3.6pl cells were resistant to apoptosis induced by gemcitabine. The addition of LY294002 or PKI 166 abrogated cell resistance to gemcitabine, whereas U0126 only partially decreased this resistance.These data demonstrate that hypoxia can induce resistance of pancreatic cancer cells to gemcitabine mainly through the PI3K/Akt/NF-kappa B pathways and partially through the MAPK(Erk) signaling pathway. Because PKI 166 prevented the activation of PI3K/Akt/NF-kappa B and MAPK(Erk) pathways, the combination of this tyrosine kinase inhibitor with gemcitabine should be an effective therapy for pancreatic cancer.
The Diagnosis of a Lienunculus
Authors: Klaus M. Bron
Journal: JAMA (1968)

The preoperative diagnosis of a lienunculus (splenunculus) was made by selective celiac arteriography in a previously splenectomized patient with hereditary spherocytosis and recurrent anemia. This represents, to our knowledge, the first report in which a lienunculus has been demonstrated using this method. It is suggested that selective splanchnic arteriography be performed whenever clinical suspicion indicates the possible presence of a lienunculus.
NIH and FDA start scheme to deliver new treatments faster
Authors: B. Roehr
Journal: BMJ (2010)

The US National Institutes of Health (NIH) and Food and Drug Administration (FDA) have formed a new collaboration “with the goal of developing more life saving cures and getting them to Americans faster,” said the federal health and human services secretary, Kathleen Sebelius, at a news conference at NIH on 24 February.

Ms Sebelius praised both agencies for their accomplishments but said, “We know we can deliver these treatments faster and safer if these agencies strengthen their partnership . . . We want to accelerate and illuminate the pathway from microscope to marketplace.”

Emerging technologies such as cell based and …
Monoclonal antibodies raised against Guillain-Barré syndrome–associated Campylobacter jejuni lipopolysaccharides react with neuronal gangliosides and paralyze muscle-nerve preparations
Authors: Carl S. Goodyear, Graham M. O’Hanlon, Jaap J. Plomp, Eric R. Wagner, Ian Morrison, Jean Veitch, Lynne Cochrane, Roland W. M. Bullens, Peter C. Molenaar, Joe Conner, Hugh J. Willison
Journal: Journal of Clinical Investigation (1999)

Guillain-Barré syndrome and its variant, Miller-Fisher syndrome, are acute, postinfectious, autoimmune neuropathies that frequently follow Campylobacter jejuni enteritis. The pathogenesis is believed to involve molecular mimicry between sialylated epitopes on C. jejuni LPSs and neural gangliosides. More than 90% of Miller-Fisher syndrome cases have serum anti-GQ1b and anti-GT1a ganglioside antibodies that may also react with other disialylated gangliosides including GD3 and GD1b. Structural studies on LPS from neuropathy-associated C. jejuni strains have revealed GT1a-like and GD3-like core oligosaccharides. To determine whether this structural mimicry results in pathogenic autoantibodies, we immunized mice with GT1a/GD3-like C. jejuni LPS and then cloned mAb's that reacted with both the immunizing LPS and GQ1b/GT1a/GD3 gangliosides. Immunohistology demonstrated antibody binding to ganglioside-rich sites including motor nerve terminals. In ex vivo electrophysiological studies of nerve terminal function, application of antibodies either ex vivo or in vivo via passive immunization induced massive quantal release of acetylcholine, followed by neurotransmission block. This effect was complement-dependent and associated with extensive deposits of IgM and C3c at nerve terminals. These data provide strong support for the molecular mimicry hypothesis as a mechanism for the induction of cross-reactive pathogenic anti-ganglioside/LPS antibodies in postinfectious neuropathies.
Large study of teratogenic potential of anticonvulsants
Authors: Beverly J. Montgomery
Journal: JAMA (1979)

Because of clinical observations regarding birth defects in children born to mothers who receive anticonvulsant therapy during pregnancy, several antiseizure agents have been implicated as human teratogens. This in turn has raised questions about the possible teratogenicity of other antiseizure agents. At the National Institute of Environmental Health Sciences (Research Triangle, Raleigh, NC), some members of the Laboratory of Environmental Toxicology have been evaluating the embryopathic potential of three classes of anticonvulsants: oxazolidones, hydantoins, and succinimides. To date, according to John Kao, PhD, Gary Shill, PhD, and Sergio Fabro, MD, PhD, 20 compounds have been tested in 4,000 different mice of one strain. Embryopathic effects have been detected for all three classes of agents. In the first of a series of reports expected on this research project, the investigators said that oxazolidone, hydantoin, and succinimide anticonvulsants were given to the mice between the eighth and tenth days of pregnancy. Estimated
Outcome of portal‐systemic shunt surgery for portal hypertension associated with intrahepatic obstruction in patients with agnogenic myeloid metaplasia
Authors: Ayalew Tefferi, Scott M. Barrett, Murray N. Silverstein, David M. Nagorney
Journal: American Journal of Hematology (1994)

Life-threatening portal hypertension (PHN) in patients with chronic myeloproliferative disorders may result from increased portal flow caused by marked splenomegaly or an increased resistance to portal flow from either a large vein thrombosis or an intrahepatic obstruction usually associated with agnogenic myeloid metaplasia (AMM). The former cause is correctable by splenectomy alone, whereas the latter requires portal-systemic shunt surgery. Few data exist regarding the outcome of portal-systemic shunt surgery in patients with AMM and intrahepatic obstruction. During the past 25 years, 13 patients with chronic myeloproliferative disorders underwent portal-systemic shunt surgery at our institution. The cause of PHN was intrahepatic obstruction in ten patients and hepatic vein thrombosis in three. Ten of the thirteen patients had AMM as initial diagnosis. Only one patient had intraoperative complications, and four patients had either sepsis or thrombosis during the postoperative period. Twelve patients survived the postoperative period and had a median postsurgical survival of 3 years (range, 0.25 to 19 years). The long-term complications of the operation were very few and included hepatic encephalopathy (one patient), portal vein thrombosis (one patient), and shunt occlusion (one patient). The procedure was successful in alleviating complications of PHN in all but one patient. Deterioration of hepatic function and subsequent hepatomegaly were unusual. Portal-systemic shunt surgery seems to be a useful option in patients with AMM and life-threatening PHN from intrahepatic obstruction.
The Disabled Veterans of World War II
Authors: Augustus Thorndike
Journal: New England Journal of Medicine (1948)

SINCE the termination of hostilities, many sick and wounded veterans have been returning to universities to complete the requirements of their college and graduate-school academic assignments, under the G. I. Bill (Public Law 346) and the Rehabilitation Bill (Public Law 16) of the Seventy-Eighth Congress. The disabled veteran has been epitomized in the press, radio and motion pictures, and although much is sponsored for his good and although many benefits have been provided for him by a generous government, it seems appropriate to call attention to what a group of six hundred disabled veterans in one of our universities represent . . .
Eosinophilic Leukemia with Fibrosing Endocarditis and Short Y Chromosome
Authors: EUGENE P. FLANNERY
Journal: Annals of Internal Medicine (1972)

Hematologic data in previous cases of eosinophilia with fibrosing endocarditis have been too limited to firmly establish a relation to the myeloproliferative disorders. A patient with the typical clinical and autopsy features of Loeffler's endocarditis also had an equally definite eosinophilic myeloproliferative disorder. The neutrophil alkaline phosphatase score, peripheral blood basophilia, serum vitamin B12, B12-binding proteins, serum muramidase, peripheral blood smear, and bone marrow and autopsy findings were all consistent with the neutrophilic type of chronic granulocytic leukemia. A presumed Philadelphia chromosome (Ph1) later proved to be a short Y chromosome, which indicates the need for physicians to be alert for its presence in males with apparent Ph1 chromosome.
Glimpses of the past
Authors: George Dunea
Journal: BMJ (2006)

Immersed in the story as I was while listening in the car on the way to work, I found myself wondering about what would happen to Mary Thorne. Was Frank Gresham going to propose or would he “marry money”? Would Mary herself give him up? I had long forgotten how it all ended, and listening to one episode at a time I felt each morning rather like Charles Dickens' readers, who would excitedly wait at the wharf …
Human T-cell leukemia virus type 2 produces a spliced antisense transcript encoding a protein that lacks a classic bZIP domain but still inhibits Tax2-mediated transcription
Authors: Marilène Halin, Estelle Douceron, Isabelle Clerc, Chloé Journo, Nga Ling Ko, Sébastien Landry, Edward L. Murphy, Antoine Gessain, Isabelle Lemasson, Jean-Michel Mesnard, Benoît Barbeau, Renaud Mahieux
Journal: Blood (2009)
Legislation is needed to stop children using sunbeds
Authors: C. S Thomson, C. Twelves
Journal: BMJ (2009)

Spence extols the joy of sunny days,1 but sunbeds raise serious issues. A recent meta-analysis showed sunbed use before the age of 35 was associated with an increased relative risk of 75% for developing malignant melanoma (absolute risks were not recorded).2

Cancer Research UK recently carried out two large, face to face surveys of sunbed use in over 9000 children aged 11-17 in England.3 …
GANGRENE FOLLOWING THROMBOSIS OF THE ABDOMINAL AORTA AND ITS BRANCHES.
Authors: R. EDWARD GARRETT
Journal: JAMA (1902)

Rarely are there offered any better opportunities for observing arteriosclerosis in all its degrees and varieties than are found among the patients of the state hospitals for the insane. In many of these institutions it is a routine practice to note the condition of the arterial system of each patient. It is now a well-established fact that arteriosclerosis is frequently hereditary and often congenital; indeed, it is not rare to find it markedly present in subjects (especially degenerates and imbeciles) as young as twelve years of age. The following case is reported not only because of its unusual occurrence, but also on account of the absence of certain pathologic lesions which one would expect to find. <h3>HISTORY.</h3><h3>The patient, Mrs.</h3> —, aged 34, was admitted to the Maryland Hospital for the Insane April 25, 1900, suffering from melancholia agitata (puerperal in origin) which is now fast terminating in dementia. <h3>Etiology.</h3>
A randomized, double-blind, vehicle-controlled study of 1% pimecrolimus cream in adult patients with perioral dermatitis
Authors: Thomas Schwarz, Inga Kreiselmaier, Thomas Bieber, Diamant Thaci, Jan C. Simon, Michael Meurer, Thomas Werfel, Torsten Zuberbier, Thomas A. Luger, Andreas Wollenberg, Matthias Bräutigam
Journal: Journal of the American Academy of Dermatology (2008)
Calciphylaxis with Arterial Calcification
Authors: Jonathan Z Li, William Huen
Journal: New England Journal of Medicine (2007)

A 53-year-old woman with diabetes mellitus and end-stage renal disease who was undergoing hemodialysis presented with fever, painful finger necrosis, and nonhealing ulceration of the legs. Hand radiographs showed no evidence of osteomyelitis but did show severely calcified arteries and the loss of soft tissue at the tips of the index and middle fingers (visible in the image, along with an intravenous catheter at the wrist). The results of skin biopsy were consistent with calciphylaxis. Calciphylaxis is a syndrome of arterial calcification and tissue necrosis that most often occurs in patients with end-stage renal disease who are undergoing hemodialysis. The . . .
Abstract 4664: Single-cell transcriptome analysis on lung squamous cell carcinoma derived from a patient
Authors: Kyu-Tae Kim, Hye-Won Lee, Kyeung Min Joo, Sang-Chul Kim, Jin-Ku Lee, Nakho Chang, Jason K. Sa, Yu Jin Cho, Do-Hyun Nam, Hae-Ock Lee, Woong-Yang Park
Journal: Cancer Research (2014)

Abstract Distinct genomic signature of a patient's cancer could provide a clue to design and predict accurate therapeutic responses to targeted medicine. Current approaches regarding heterogeneous cancer cells en masse as a pooled population, however, hardly reflect complete genomic landscape of tumor diversity, missing potentially important minor clones' implications regarding metastasis and drug resistance. Here we report a comprehensive analysis to discover different patterns of subclonal behaviors in functional modalities and signaling pathways out of heterogeneous population derived from a patient with lung squamous cell carcinoma, using single-cell mRNA sequencing. As a result of nonnegative matrix factorization as a clustering, we identified discrete 4 subgroups with a major group in accordance with overall expression profile of a pooled population of cells, and the other 3 minor groups that were masked in a pooled sample. Genomic variants were also reliably identified and compared across single cells. We integrated these genomic signatures from single cells to address the different responses in drug screening. Together, our approach provides insights into the more accurate strategy to identify minor but potentially important subclones that are relevant to drug resistance. Citation Format: Kyu-Tae Kim, Hye-Won Lee, Kyeung Min Joo, Sang-Chul Kim, Jin-Ku Lee, Nakho Chang, Jason K. Sa, Yu Jin Cho, Do-Hyun Nam, Hae-Ock Lee, Woong-Yang Park. Single-cell transcriptome analysis on lung squamous cell carcinoma derived from a patient. [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 4664. doi:10.1158/1538-7445.AM2014-4664
Soft-Tissue Sarcomas, Breast Cancer, and Other Neoplasms
Authors: FREDERICK P. LI
Journal: Annals of Internal Medicine (1969)

Four families were identified in which a pair of children had soft-tissue sarcomas: three sets of sibs and one set of cousins. One parent of each affected child developed cancer; carcinoma of the breast occurred in three mothers under 30 years of age. Other young adults in these families had a high frequency of cancer, with no evidence of underlying genetic disorders known to carry a high risk of neoplasia. The increased familial susceptibility to cancer was manifested not only by the large number of members affected but by a seeming excess of multiple primary neoplasms. These findings suggest a new "familial" syndrome of neoplastic diseases in which heredity or oncogenic agents, or both, may have a causal role.
German health insurers are urged to pay rebates to members as surplus reaches record high
Authors: N. Stafford
Journal: BMJ (2012)

Germany’s huge state health insurance system is continuing the recent trend of collecting more money than it is spending, posting a surplus of €2.7bn (£2.2bn; $3.5bn) in the first half of 2012, the German health ministry has said.1

The system, made up of independent insurers regulated by the government and covering around 90% of the population, collected €94.82bn in premiums in the first half of 2012 and spent €92.13bn.

This first six month surplus of €2.7bn compares with a full year surplus last year of €4bn and suggests that the total surplus for 2012 will exceed last year’s.

The ministry …
Transventricular Mitral Valvotomy
Authors: FRANK GERBODE
Journal: Circulation (1960)

In a consecutive series of 200 operations for relief of mitral stenosis, transventricular valvotomy was performed whenever digital valvotomy was found to be ineffective. The operative mortality was 12.5 per cent. In a series of 17 second operations for mitral stenosis, the transventricular method was similarly used, with 2 operative deaths. A left lateral thoracotomy was employed, with reentry through the left atrium. The results of transventricular valvotomy were more satisfactory than when the usual commissurotomy through the left atrium was employed.
Liver–Lung Interactions Following <i>Escherichia coli</i>Bacteremic Sepsis and Secondary Hepatic Ischemia/Reperfusion Injury
Authors: GEORGE M. MATUSCHAK, KURT A. HENRY, CHERYL A. JOHANNS, ANDREW J. LECHNER
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We hypothesized that ischemia/reperfusion (I/R) injury of the liver during normotensive gram-negative bacteremic sepsis alters the kinetics of circulating endotoxin, tumor necrosis factor-alpha (TNF- α ), and coinduced mediators, thereby exacerbating sepsis-induced lung inflammation. Liver and lung dysfunction were studied after hematogenous infection of Sprague-Dawley rats with 109 Escherichia coli serotype O55:B5 (EC) and 90 min of secondary hepatic ischemia in EC + I/R and saline-infused (normal saline NS) × I/R rats, followed by brief (1 h) or longer reperfusion (24 h). TNF- α :leukotriene interactions in this model were examined using the 5-lipoxygenase-activating protein inhibitor MK-886. Compared with sham-operated EC + Sham animals, peak serum endotoxin, TNF- α , alanine aminotransferase, interleukin-6 (IL-6), and hepatic neutrophil (PMN) influx were higher in EC + I/R rats through 24 h (p < 0.05) despite comparable arterial pressure. Lung PMN influx and wet/dry weight ratios were likewise enhanced in EC + I/R versus EC + Sham or NS + I/R rats. MK-886 attenuated TNF- α concentrations and ischemic liver injury but not mortality. Thus, focal hepatic I/R augments circulating endotoxin, TNF- α , and postbacteremic lung inflammation early after normotensive E. coli bacteremic sepsis.
The Effects of Mandatory Prescribing of Thiazides for Newly Treated, Uncomplicated Hypertension: Interrupted Time-Series Analysis
Authors: Atle Fretheim, Kari Håvelsrud, Graeme MacLennan, Doris Tove Kristoffersen, Andrew D Oxman
Journal: PLoS Medicine (2007)

Background The purpose of our study was to evaluate the effects of a new reimbursement rule for antihypertensive medication that made thiazides mandatory first-line drugs for newly treated, uncomplicated hypertension. The objective of the new regulation was to reduce drug expenditures. Methods and Findings We conducted an interrupted time-series analysis on prescribing data before and after the new reimbursement rule for antihypertensive medication was put into effect. All patients started on antihypertensive medication in 61 general practices in Norway were included in the analysis. The new rule was put forward by the Ministry of Health and was approved by parliament. Adherence to the rule was monitored only minimally, and there were no penalties for non-adherence. Our primary outcome was the proportion of thiazide prescriptions among all prescriptions made for persons started on antihypertensive medication. Secondary outcomes included the proportion of patients who, within 4 mo, reached recommended blood-pressure goals and the proportion of patients who, within 4 mo, were not started on a second antihypertensive drug. We also compared drug costs before and after the intervention. During the baseline period, 10% of patients started on antihypertensive medication were given a thiazide prescription. This proportion rose steadily during the transition period, after which it remained stable at 25%. For other outcomes, no statistically significant differences were demonstrated. Achievement of treatment goals was slightly higher (56.6% versus 58.4%) after the new rule was introduced, and the prescribing of a second drug was slightly lower (24.0% versus 21.8%). Drug costs were reduced by an estimated Norwegian kroner 4.8 million (€0.58 million, US$0.72 million) in the first year, which is equivalent to Norwegian kroner 1.06 per inhabitant (€0.13, US$0.16). Conclusions Prescribing of thiazides in Norway for uncomplicated hypertension more than doubled after a reimbursement rule requiring the use of thiazides as the first-choice therapy was put into effect. However, the resulting savings on drug expenditures were modest. There were no significant changes in the achievement of treatment goals or in the prescribing of a second antihypertensive drug.
Postgraduate Training Posts for Overseas Doctors
Authors: W. M. C. Allen
Journal: BMJ (1966)

falcipariem parasites were found in the blood after 19 months' stay away from a malarious zone.It is interesting to note that the patient in Walters's report was also five months pregnant.McGregor and Smith2 found that primigravidae seemed to lose immunity against P. falciparum, and Bruce- Chwatt3 observed an increased parasite density during parturition.These two cases tend to support the suggestion that pregnancy might predispose to clinical recrudescence of P. falciparuni malaria.In view of the com- plications associated with this infection great vigilance in detecting and treating it during the antenatal period is necessary.
What I might have been
Authors: S. Ruben
Journal: BMJ (1996)

The past 37 years have been shaped and overshadowed by the fact that I have a minor disability. I am dystonic down the left side of my body and until recently I thought that this was due to a structural lesion in my basal ganglia, caused by the measles virus. I only asked my general practitioner if I could be referred to another neurologist to help me justify my decision to finally apply for a disabled sticker for my car.

I had not seen a neurologist for 10 years and had come to terms with my diagnosis as best I could, but I needed an expert's permission for the orange badge. I have always resisted artificial aids, preferring to stagger about, although I had reluctantly started using a stick for long walks and evenings, which are my worst time.

I have seen neurologists on and off all my life. As a small child in Belfast my initial diagnosis was made by a wonderful doctor, Louis Herwitz, who has been a lifelong inspiration to me. He was the adult who encouraged rather than restricted me. He always spoke to me not my …