tbuckley/cabot-search huggingface dataset:
Familial pachyonychia congenita with steatocystoma multiplex and multiple abscesses of the scalp due to the p.Asn92Ser mutation in keratin 17
Authors: J. Ofaiche, S. Duchatelet, S. Fraitag, A. Nassif, J. Nougué, A. Hovnanian
Journal: British Journal of Dermatology (2014)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Pachyonychia congenita (PC) is a rare genodermatosis transmitted as an autosomal dominant trait that is caused by mutations in the differentiation‐specific keratin genes KRT6a (52%), KRT6b (3%), KRT16 (28%) or KRT17 (17%), which are expressed in the nails, skin, oral mucosa, larynx, hair and teeth.1 Approximately 1000 patients with PC have been identified, of whom 400 have been confirmed genetically to have it. Two subtypes have been classically described: PC‐1 (Jadassohn–Lewandowsky type, OMIM#167200), caused by mutations in KRT6a or KRT16, with predominant oral leucokeratosis and palmoplantar keratoderma; and PC‐2 (Jackson–Lawler type, OMIM#167210) resulting from mutations in KRT6b or KRT17, with neonatal teeth, pili torti and multiple cysts.2 3 The presence of multiple sebaceous cysts [steatocystoma multiplex (SM)] at puberty has been proposed to differentiate PC‐2 from PC‐1,2 3 but it is now recognized that there is a considerable overlap between the two classical subtypes of PC, and a new classification based on the mutated keratin gene has now been proposed (PC‐6a, PC‐6b, PC‐16 and PC‐17).4 5
Atypical Femoral Head Osteonecrosis
Authors: Francesco Giammarile, Fahad Ghozzy, Isabelle Morelec, Claire Houzard, Chadi Hlaihel, Julien Clechet, Frédéric Paycha
Journal: Clinical Nuclear Medicine (2011)

We report the case of a 65-year-old man presented with polymyalgia rheumatica. After a week on corticosteroid (40 mg/d), pain was relieved rapidly. Bone scan, requested to precisely localize osteoarticular lesions, showed high uptake in the external aspect of the head of left femur. In the clinical setting, bone scan and MRI appearances are suggestive of osteonecrosis, probably of recent onset. The final diagnosis of atypical necrosis of the femoral head, most probably secondary to corticoid therapy, was thus established.
A DANGEROUS PREPARATION OF DIGITALIS
Authors: JOHN WYCKOFF
Journal: JAMA (1930)

Some time ago a committee<sup>1</sup>was formed at Bellevue Hospital for the systematic investigation of the value of digitalis in pneumonia. In the course of the work observations were made bearing on the subject of the potency of digitalis, bringing vividly to attention several points of great practical importance to the physician. A brief summary of these observations on potency is presented in this preliminary communication.<sup>2</sup> Several hundred patients were studied and divided into comparable groups of untreated controls and those receiving digitalis. The drug was administered in full dosage by an approved technic; namely, 0.15 cat unit per pound of body weight in twenty-four hours. Two well known commercial specimens of digitalis were employed. The committee at first accepted the potency of both preparations as labeled by the manufacturers, which stated one to be about 50 per cent more potent than the other. This was taken into
Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in normal adult hematopoiesis.
Authors: C Labbaye, M Valtieri, T Barberi, E Meccia, B Masella, E Pelosi, G L Condorelli, U Testa, C Peschle
Journal: Journal of Clinical Investigation (1995)

We have explored the expression of the transcription factors GATA-1, GATA-2, and NF-E2 in purified early hematopoietic progenitor cells (HPCs) induced to gradual unilineage erythroid or granulocytic differentiation by growth factor stimulus. GATA-2 mRNA and protein, already expressed in quiescent HPCs, is rapidly induced as early as 3 h after growth factor stimulus, but then declines in advanced erythroid and granulocytic differentiation and maturation. NF-E2 and GATA-1 mRNAs and proteins, though not detected in quiescent HPCs, are gradually induced at 24-48 h in both erythroid and granulocytic culture. Beginning at late differentiation/early maturation stage, both transcription factors are further accumulated in the erythroid pathway, whereas they are suppressed in the granulopoietic series. Similarly, the erythropoietin receptor (EpR) is induced and sustainedly expressed during erythroid differentiation, although beginning at later times (i.e., day 5), whereas it is barely expressed in the granulopoietic pathway. In the first series of functional studies, HPCs were treated with antisense oligomers targeted to transcription factor mRNA: inhibition of GATA-2 expression caused a decreased number of both erythroid and granulocyte-monocytic clones, whereas inhibition of NF-E2 or GATA-1 expression induced a selective impairment of erythroid colony formation. In a second series of functional studies, HPCs treated with retinoic acid were induced to shift from erythroid to granulocytic differentiation (Labbaye et al. 1994. Blood. 83:651-656); this was coupled with abrogation of GATA-1, NF-E2, and EpR expression and conversely enhanced GATA-2 levels. These results indicate the expression and key role of GATA-2 in the early stages of HPC proliferation/differentiation. Conversely, NF-E2 and GATA-1 expression and function are apparently restricted to erythroid differentiation and maturation: their expression precedes that of the EpR, and their function may be in part mediated via the EpR.
ROLE OF KV1.3 CHANNELS IN INTIMAL HYPERPLASIA
Authors: Merc&egrave; Roqu&egrave;. Laura Novensa, Pilar Cidad, Montserrat Batlle, Eduardo Miguel-Velado, Esperanza Alonso, Teresa P&eacute;rez-Garc&iacute;a, Jos&eacute; Ram&oacute;n L&oacute;pez, Magda Heras
Journal: Journal of the American College of Cardiology (2012)
Effect of a Low-Carbohydrate Diet on Appetite, Blood Glucose Levels, and Insulin Resistance in Obese Patients with Type 2 Diabetes
Authors: Guenther Boden, Karin Sargrad, Carol Homko, Maria Mozzoli, T. Peter Stein
Journal: Annals of Internal Medicine (2005)

It is not known how a low-carbohydrate, high-protein, high-fat diet causes weight loss or how it affects blood glucose levels in patients with type 2 diabetes.To determine effects of a strict low-carbohydrate diet on body weight, body water, energy intake and expenditure, glycemic control, insulin sensitivity, and lipid levels in obese patients with type 2 diabetes.Inpatient comparison of 2 diets.General clinical research center of a university hospital.10 obese patients with type 2 diabetes.Usual diets for 7 days followed by a low-carbohydrate diet for 14 days.Body weight, water, and composition; energy intake and expenditure; diet satisfaction; hemoglobin A1c; insulin sensitivity; 24-hour urinary ketone excretion; and plasma profiles of glucose, insulin, leptin, and ghrelin.On the low-carbohydrate diet, mean energy intake decreased from 3111 kcal/d to 2164 kcal/d. The mean energy deficit of 1027 kcal/d (median, 737 kcal/d) completely accounted for the weight loss of 1.65 kg in 14 days (median, 1.34 kg in 14 days). Mean 24-hour plasma profiles of glucose levels normalized, mean hemoglobin A1c decreased from 7.3% to 6.8%, and insulin sensitivity improved by approximately 75%. Mean plasma triglyceride and cholesterol levels decreased (change, -35% and -10%, respectively).The study was limited by the short duration, small number of participants, and lack of a strict control group.In a small group of obese patients with type 2 diabetes, a low-carbohydrate diet followed for 2 weeks resulted in spontaneous reduction in energy intake to a level appropriate to their height; weight loss that was completely accounted for by reduced caloric intake; much improved 24-hour blood glucose profiles, insulin sensitivity, and hemoglobin A1c; and decreased plasma triglyceride and cholesterol levels. The long-term effects of this diet, however, remain uncertain.
Prolonged Fasting Hypoglycemia Due to Insulin Antibodies in Patient With Non-Insulin-Dependent Diabetes Mellitus: Effect of Insulin Withdrawal on Insulin-Antibody—Binding Kinetics
Authors: Timon W Van Haeften, Bethany A Krom, John E Gerich
Journal: Diabetes Care (1987)

Fasting hypoglycemia, which persisted for 3 days after insulin treatment was stopped, occurred in a patient with non-insulin-dependent diabetes mellitus who had inappropriate plasma free-insulin levels (18-25 microU/ml) and extremely high antibody-bound insulin (greater than 20,000 microU/ml) but normal counter-regulatory hormone secretion and plasma C-peptide levels. The amount of antibody-bound insulin decreased in a biphasic pattern over 13 mo of observation with an initial half-life of 35 days and a more gradual decrease with a half-life of 160 days. The number of high-affinity antibody binding sites was virtually identical to the amount of antibody-bound insulin in the patient's plasma. We conclude that the patient's fasting hyperinsulinemia and hypoglycemia were due to release of antibody-bound insulin.
Changes in calcium fluxes in mitochondria, microsomes, and plasma membrane vesicles of livers from monosodium l-glutamate–obese rats
Authors: Monique Cristine de Oliveira, Rosana Torrezan, Cecília Edna Mareze da Costa, Célia Regina Ambiel, Rodrigo Polimeni Constantin, Emy Luiza Ishii-Iwamoto, Clairce Luzia Salgueiro-Pagadigorria
Journal: Metabolism (2011)

The purpose of this work was to evaluate if the fat liver accumulation interferes with intracellular calcium fluxes and the liver glycogenolytic response to a calcium-mobilizing α1-adrenergic agonist, phenylephrine. The animal model of monosodium l-glutamate (MSG)–induced obesity was used. The adult rats develop obesity and steatosis. Calcium fluxes were evaluated through measuring the 45Ca2+ uptake by liver microsomes, inside-out plasma membrane, and mitochondria. In the liver, assessments were performed on the calcium-dependent glycogenolytic response to phenylephrine and the glycogen contents. The Ca2+ uptake by microsomes and plasma membrane vesicles was reduced in livers from obese rats as a result of reduction in the Ca2+-ATPase activities. In addition, the plasma membrane Na+/K+-ATPase was reduced. All these matched effects could contribute to elevated resting intracellular calcium levels in the hepatocytes. Livers from obese rats, albeit smaller and with similar glycogen contents to those of control rats, released higher amounts of glucose in response to phenylephrine infusion, which corroborates these observations. Mitochondria from obese rats exhibited a higher capacity of retaining calcium, a phenomenon that could be attributed to a minor susceptibility of the mitochondrial permeability transition pore opening.
Epidermal Growth Factor Receptor Inhibitors and Antiangiogenic Agents for the Treatment of Non-Small Cell Lung Cancer
Authors: Leora Horn, Alan Sandler
Journal: Clinical Cancer Research (2009)

Non-small cell lung cancer (NSCLC) is a major global health problem and represents the leading cause of cancer-related deaths worldwide. The majority of patients with NSCLC are diagnosed with advanced-stage disease, and the prognosis for such patients is poor. The currently approved cytotoxic chemotherapy is associated with substantial limitations in both efficacy and safety. The availability of agents targeted against the epidermal growth factor receptor (EGFR), as well as the antiangiogenic agent bevacizumab, have provided some clinical benefit. Nonetheless, the efficacy of these agents is also inadequate, and resistance has emerged as a clinical problem. Numerous novel targeted therapies are now in clinical development and may have potential for overcoming the limitations associated with currently available agents. In this article we review clinical data for molecular-targeted therapies in NSCLC, with emphasis on EGFR inhibitors and antiangiogenic agents.
Mcl-1L cleavage is involved in TRAIL-R1– and TRAIL-R2–mediated apoptosis induced by HGS-ETR1 and HGS-ETR2 human mAbs in myeloma cells
Authors: Emmanuelle Menoret, Patricia Gomez-Bougie, Alexandrine Geffroy-Luseau, Sylvanne Daniels, Philippe Moreau, Steven Le Gouill, Jean-Luc Harousseau, Regis Bataille, Martine Amiot, Catherine Pellat-Deceunynck
Journal: Blood (2006)
GPs and long term mentally ill patients.
Authors: J Crammer
Journal: BMJ (1991)

his cervical spine suggested an extensive posterior ligament tear with instability at the level of C6-7.His injury was initially treated with a firm polythene neck collar.Subsequent flexion and extension radiographs showed instability with sub- luxation of C6 on C7.This was stabilised by bone grafting and fixation with Halifax hooks.Spinal injuries that result from diving accidents are underreported and not confined to water sports.As noted by Mr Grundy and colleagues, alcohol and bravado compound this problem.Pop events may provide the right ingredients for such accidents to occur.
Why dost thou use me thus? I know thee not
Authors: G. G. Liddle
Journal: JAMA (1966)

To the Editor:—  Large dictionaries give 22 definitions for  as a verb or 23 as a noun, or more or less. Your journal invents still others in each issue. Shakespeare (The Bard of Avon) managed with three. As cited above, verbally use is followed immediately by a (pro)-noun; it is a transitive verb of action. Similarly the first meaning as a noun implies action.  ... 103 patients have now been examined... using... the scintillation camera...  If you think it was clever of that doctor to examine his patients stooped over the camera, try again.  ... results were obtained using a scintillation camera...  Nobody obtained the result; nobody used the camera, but results were obtained just the same. And that's not all.  ... brain scans... using 99mTc in the pertechnetate form.  Obviously a new meaning has been derived, which describes ordinary actions in kindergarten English, oc
The Diagnosis of Hysteria: What Are We Trying to Do?
Authors: SAMUEL B. GUZE
Journal: American Journal of Psychiatry (1967)

The diagnosis of a "functional" psychiatric illness may be considered valid if the patients do not develop the features of a different illness, if they have a similar clinical course, and if an increased prevalence of the same disorder is encountered among their relatives. Diagnostic validity thus requires follow-up and family studies. Using these principles, the author summarizes his studies of hysteria and delineates the diagnostic criteria that have been appropriately validated.
Murine tissue amyloid protein AA. NH2-terminal sequence identity with only one of two serum amyloid protein (ApoSAA) gene products.
Authors: J S Hoffman, L H Ericsson, N Eriksen, K A Walsh, E P Benditt
Journal: The Journal of Experimental Medicine (1984)

Amyloid protein AA is the presumptive fragment of an acute phase serum apolipoprotein, apoSAA. Two major murine apoSAA isotypes (apoSAA1 and apoSAA2) have been identified. The NH2-terminal amino acid sequences of purified murine apoSAA1 and apoSAA2 have been examined and compared with that of murine amyloid protein AA. Our results indicate that apoSAA1 and apoSAA2 are separate gene products and that amyloid protein AA has NH2-terminal amino acid sequence identity with only one of these isotypes, namely apoSAA2.
Economy in the Treatment of Impetigo and Scabies
Authors: R. W. Carslaw, J. A. Swenarton
Journal: BMJ (1941)

MEDICAL JOURNAL25amide group causes so much scarring and deposit of fibrous tissue that it hinders efficient drainage.This may be said to be a sweeping statement when founded on two cases, but a similar condition can be seen in cases of mastoid abscess that have had large doses of these drugs.There- fore in future cases of deep neck infection I should operate first and then use the sulphonamide group in large doses by mouth, parenterally, or by packing the wound, with the proviso that my operative drainage should be extensive and that it entirely covered any region likely to be infected.5. The direction of spread of the infection and places that should be inspected for possible infection need not be gone into here.Mosher (1929) has described these matters in detail.It is as well to complete the drainage of the neck region in the one operation, as a second attack may have to be done with landmarks lost in fibrous tissue and difficult to find.
Genetic polymorphisms in interferon pathway and response to interferon treatment in hepatitis B patients: A pilot study
Authors: J King
Journal: Hepatology (2002)

Interferon alfa (IEN-α) therapy remains a mainstay of treatment in active hepatitis B. However, sustained remission rates remain relatively low, and the search for factors important for response to therapy continues. Our study aimed to identify the host single nucleotide polymorphisms (SNPs) that predict IFN response in hepatitis B patients. We selected genes in the IFN pathway involved in antiviral and signaling activities and sequenced 22 SNPs for each of our 82 patients. Our results identified 2 SNPs in the antiviral pathway that may influence IFN response. One SNP in the regulatory region of the eIF-2α gene revealed A/G alleles. The rate of A/G heterozygotes is 22% in nonresponders (NR) and 2% in sustained responders (R), with an odds ratio (OR) of 12.82 (95% CI: 1.52–107.85, P = 0.009). After adjustment for age, sex, and HBV DNA level, the OR reaches 14.94 (95% CI: 1.45–153.71, P = 0.023). This marker revealed greater significance than HBV DNA levels (OR 5, 95% CI: 1.01–2.43, P = 0.033) as a marker for IFN response, suggesting its potential advantage over conventional predictors. In addition, borderline significance for the SNP in MxA gene promoter at nt –88 revealed G/T alleles, with the G/T heterozygote rate being 19% in nonresponders and 43% in sustained R (P = 0.061), concurring with a previous study involving hepatitis C patients. In conclusion, this pilot identified SNPs as potential markers that could predict hepatitis B patient response. These observations may help guide future large-scale studies in examining host SNPs for their clinical utility in predicting IFN response. (HEPATOLOGY2002;36:1416–1424).
Cytosolic calcium staircase in ventricular myocytes isolated from guinea pigs and rats
Authors: Y. Hattori, J. Toyama, I. Kodama
Journal: Cardiovascular Research (1991)

Study objective — The aim was to study intracellular calcium dynamics underlying positive or negative tension staircase of mammalian hearts. Design — Changes in cytosolic calcium concentration ([Ca2+]i) in single ventricular myocytes were investigated using a Ca2+ indicator, fura-2. Beat to beat alterations in fura-2 fluorescence and cell edge movement on resumption of stimulation were recorded on video tape, and analysed by a computer based image processing system. Experimental material — Single ventricular myocytes were enzymatically isolated from the hearts of 30 adult guinea pigs and 25 adult rats. Measurements and main results — In guinea pig ventricular myocytes, the positive contractile staircase was associated with ascending staircases of both peak systolic and end diastolic [Ca2+]i because of a cumulative increase in diastolic [Ca2+]i. In rat ventricular myocytes, the negative contractile staircase was accompanied by a descending staircase of peak systolic [Ca2+]i, while end diastolic [Ca2+]i level was unchanged due to the rapid decay of [Ca2+]i transients. Ryanodine (10 μM) reversed the mode of [Ca2+]i and contractile staircases from negative to positive in rat myocytes, whereas it caused minimal alteration in guinea pig myocytes. Conclusions — Tension staircase of mammalian hearts depends on diastolic Ca2+ level as well as Ca2+ handling by the sarcoplasmic reticulum. The positive staircase may require progressive increase in diastolic [Ca2+]i, while the negative staircase may be mediated by depletion of activator Ca2+ in the sarcoplasmic reticulum.
Abstract 3103: Differences in the DDR enzymes activation kinetics between normal and cancer cells could be utilized to achieve targeted cellular sensitivity towards genotoxic agents
Authors: Hilal S. Khalil, Hemanth Tummala, Tedd Hupp, Nikolai Zhelev
Journal: Cancer Research (2012)

Abstract The DNA damage response (DDR) pathway is a complex signalling network that is activated when eukaryotic cells undergo DNA damage caused by exposure to genotoxic agents. Depending upon the type and scale of DNA damage, the DDR can either cause cell cycle arrest if the DNA lesions are repairable, or trigger apoptosis if the DNA lesions are beyond the repair capacity of the cell. A variety of enzymes take part in this complex signalling network that decides cellular fate after DNA damage, and is comprised of kinases, phosphatases and glycosylases. Here we explored the kinetics of activation of these key enzymes, the rates of their product formation and the interplay between them that impact the decision making process of the cell. We exposed normal (MCF10A, HaCat) and breast cancer cell lines (MCF7, MDA MB231, MDA MB468) to different combinations of radiomimetic drugs, UV radiation and enzyme inhibitors in a time and dose dependent manner and looked at the resulting enzyme activation rates of DDR kinases such as ATM, ATR, Chk1, Chk2, and DDR phosphatases PP2A and WIP1. We studied the effects of such enzymatic activation on their substrates P53, E2F1, BRCA1 and γ-H2AX and examined its outcome on cell survival. Firstly, we have identified key differences in enzyme activation kinetics that impacted the cell fate decision between normal and cancer cell lines. In addition we established treatment regimes based on those differences that bias the cell fate decision towards apoptosis in cancer cells and cell cycle arrest and repair of DNA in their normal counterparts. Thus, we have demonstrated a link between the rate of induction of different enzyme activities in the DDR pathway, the resulting product formation and cellular sensitivity to genotoxic agents. We have successfully used such information to devise a combinatorial drug treatment regime that is selective for cancer cells. Elucidation of the enzyme activation kinetics in a time and dose dependent manner of the proteins governing cell fate decision can be used to achieve targeted cellular selectivity and sensitivity with lesser side effects on normal cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3103. doi:1538-7445.AM2012-3103
OUTCOMES OF INOPERABLE PATIENTS UNDERGOING TRANSAPICAL AND TRANSAORTIC TRANSCATHETER AORTIC VALVE REPLACEMENT: A PARTNER 2B SUBSTUDY ANALYSIS OF NESTED REGISTRIES
Authors: Mathew Williams, Susheel Kodali, Darshan Doshi, Hersh Maniar, William Fearon, Joseph Bavaria, Michael Davidson, Augusto Pichard, Alan Zajarias, Lars Svensson, Samir Kapadia, Charanjit Rihal, Kevin Greason, Vinod Thourani, Hung-Ir Li, Martin Leon, Vasilis Babaliaros
Journal: Journal of the American College of Cardiology (2014)