tbuckley/cabot-search huggingface dataset:
A strange case of familial atopy
Authors: T. Roscoe
Journal: BMJ (2002)

<h3>Abstract</h3> <h3>Background</h3> Over the last decades, malaria parasites have been rapidly developing resistance against antimalarial drugs, which underlines the need for novel drug targets. Thioredoxin reductase (TrxR) is crucially involved in redox homeostasis and essential for Plasmodium falciparum. In this communication, we report first time important Docking study by in Silico approach, using AutoDock Vina. After a selective analysis of over 300 drugs, processed with Pyrx (a Virtual Screening software into the active site of protein (ID PDB 4J56 Thioredoxin reductase 2 Chain A), we noticed excellent value of Binding Energy of Telatinib estimated by Pyrx software. These results are comparable to the crystallized ligand FAD (FLAVIN-ADENINE DINUCLEOTIDE) completed in the above-mentioned protein. Indeed, from the results of Autodock Vina, Telatinib an inhibitor of tyrosine kinases, has excellent a Binding affinity value, ca. −12 kcal/mol.
Emergency stenting for acute occlusion after coronary balloon angioplasty.
Authors: U Sigwart, P Urban, S Golf, U Kaufmann, C Imbert, A Fischer, L Kappenberger
Journal: Circulation (1988)

Acute coronary artery occlusion complicates 2-12% of the balloon angioplasty procedures, and despite repeat angioplasty, emergency surgical revascularization is often necessary. We report our initial experience with the emergency implantation of endoluminal stents for acute vessel closure after coronary balloon angioplasty. Nine patients received one stent, and two patients received two stents during the study period. Implantation was technically successful in all patients; there were no deaths, no myocardial infarctions as evidenced by Q wave on the electrocardiogram, and no need for emergency surgery. One additional patient, not satisfying the study inclusion criteria, died 16 hours after stent implantation from left ventricular failure and intractable arrythmias. Two patients in the study group had a moderate creatinine phosphokinase rise during the first 48 hours after implantation. During a median follow-up period of 3 months (range, 1-20 months), there have been no deaths and no need for elective coronary bypass surgery. One patient required emergency recanalization 3 months after implantation because of acute occlusion of the stented segment with limited myocardial infarction. Six patients have undergone control angiography, and none has developed chronic restenosis within the stented segment. For selected patients, coronary artery stenting appears to be a promising alternative to emergency bypass surgery after acute vessel occlusion during balloon angioplasty.
RENAL COMPLICATIONS DUE TO SULFATHIAZOLE
Authors: Curtis F. Garvin
Journal: JAMA (1941)

Urinary complications due to sulfathiazole have been described in animals<sup>1</sup>and in man.<sup>2</sup>At the Cleveland City Hospital, of fifty-four patients with pneumonia treated with sulfathiazole,<sup>3</sup>thirty-three (61.1 per cent) had crystals of the drug in the urine. In a control series of fifty-six patients treated with sulfapyridine, sixteen (28.6 per cent) had crystals in the urine. This difference is statistically highly significant.<sup>4</sup> Sulfathiazole crystals appear in the urine more often than sulfapyridine probably because sulfathiazole is excreted more rapidly and hence a greater amount of the drug has to be administered in order to maintain a satisfactory concentration in the blood. In the cases under consideration an average dose of 52.4 Gm. of sulfathiazole administered over an average period of 5.2 days produced an average blood concentration of 5.8 mg. per hundred cubic centimeters of the free drug in the blood. In the cases treated
Amikacin Therapy for Serious Gram-Negative Bacillary Infections
Authors: RICHARD D. MEYER
Journal: Annals of Internal Medicine (1975)

Amikacin is a new aminoglycoside antibiotic pharmacologically similar to kanamycin. It has a wide range of activity against Gram-negative bacilli, including many resistant to gentamicin. Thirty-six serious Gram-negative bacillary infections were treated with amikacin. Twenty-nine patients (80-6%) responded (cured or improved). Twelve of 13 patients with gentamicin-resistant pathogens responded. Minor ototoxicity occurred in 6 patients and was associated with prolonged therapy or previous aminoglycoside therapy. Possible nephrotoxicity with amikacin was found in 6 patients. Amikacin should be used primarily to treat suspected or known gentamicin-resistant pathogens.
377 The ecto-nucleotidase NTPDase2 selectively down-regulated in biliary fibrosis
Authors: E KRUGLOV, J TOURE, M NAUMANJHANDIER, D JAIN, J SEVIGNY, S ROBSON, J DRANOFF
Journal: Hepatology (2003)

Endogenous Plastic Somatic (ePS) cells isolated from adult human tissues exhibit extensive lineage plasticity in vitro and in vivo. Here we visualize these rare ePS cells in a latent state, i.e. lacking SOX2, OCT3/4 and NANOG (SON) expression, in non-diseased breast specimens through immunohistochemical analysis of previously identified ePS-specific biomarkers (CD73+, EpCAM+ and CD90−). We also report a novel mechanism by which these latent ePS cells acquire SON expression and plasticity in vitro. Four extracellular factors are necessary for the acquisition of SON expression and lineage plasticity in ePS cells: adenosine (which is produced by the 5′ ecto-nucleotidase CD73 and activates in turn the PKA-dependent IL6/STAT3 pathway through the adenosine receptor ADORA2b), IL6, FGF2 and ACTIVIN A. Blocking any pathway component renders ePS cells incapable of SON expression and lineage plasticity. Notably, hESCs do not use adenosine or IL6 nor they express CD73 or ADORA2b and inhibition of adenosine signaling does not ablate their plasticity. Therefore, the data presented here delineate novel circuitry and physiological signals for accessing SON expression in rare, undifferentiated human cells.
Evaluation of the nitrosamine hypothesis of gastric carcinogenesis in precancerous conditions.
Authors: C N Hall, D Darkin, R Brimblecombe, A J Cook, J S Kirkham, T C Northfield
Journal: Gut (1986)

A 24 hour gastric aspiration study was carried out on nine Polya gastrectomy, eight pernicious anaemia, and nine matched control subjects. Intragastric pH, bacteria, nitrite, and N-nitroso compounds were assessed half hourly whilst ambulant and hourly when in bed. Both total and nitrate reducing bacterial counts were positively related to pH (chi 2 = 279.3; p less than 0.001), as was nitrite concentration (F = 19.1; p less than 0.0001). By contrast, total (F = 40.6; p less than 0.0001) and stable (F = 257.4; p less than 0.0001) N-nitroso compound concentrations were negatively related to pH. Clear differences in these gastric juice factors were not apparent between matched control and either pernicious anaemia, or Polya gastrectomy because the Polya gastrectomy and matched control groups were heterogeneous for gastric acidity. Thus, although eight of eight pernicious anaemia subjects were hypoacidic (defined as intragastric pH greater than 4 for greater than 50% of both daytime and night time periods), only five of nine Polya gastrectomy and two of nine matched control subjects were hypoacidic. When subjects were rearranged into hypoacidic (n = 15) and acidic (n = 11) groups, bacterial counts (p less than 0.01) and nitrite concentrations (p less than 0.01) were higher, whereas N-nitroso compounds tended to be lower (NS) in the hypoacidic group. These data suggest that, although hypoacidity predisposes to bacterial overgrowth and nitrite generation, it does not enhance nitrosation. Instead, this is maximal at low pH, suggesting chemical rather than bacterial nitrosation, contrary to the nitrosamine hypothesis of gastric carcinogenesis.
Implied Consent for Cadaveric Organ Donation
Authors: Thomas E. Starzl
Journal: JAMA (1984)

Few issues in medicine have received more attention recently than the need for cadaveric organ donation. In the study by Overcast et al,<sup>1</sup>published in this issue, the influence and effect of donor card programs on organ procurement was examined and found to be inconsequential. This negative conclusion is apt to dampen the enthusiasm of legislators in states where active consideration is being given to laws that would permit or even require a statement about potential organ donation on a driver's license. This would be unfortunate since the driver's license programs have had a full trial only in the state of Colorado. There, almost two thirds of all drivers are self-designated as donors compared with other states with one fiftieth to one eighth this number. In Colorado, the donors' license program was only one component of a long-range effort at public education and legal reform that included a Uniform
Safety of Sublingual Latex Immunotherapy. Are Specific IgE to Recombinant Latex Allergens a Risk Factor?
Authors: A. Spínola Santos, M. Branco Ferreira, A. Lopes Pregal, S. Lopes da Silva, A. Mendes, E. Pedro, F. Nunes, M.L. Palma-Carlos, M.C. Santos, A.G. Palma-Carlos, M. Pereira Barbosa
Journal: Journal of Allergy and Clinical Immunology (2006)
ΔF508 CFTR protein expression in tissues from patients with cystic fibrosis
Authors: Nanette Kälin, Andreas Claaß, Martin Sommer, Edith Puchelle, Burkhard Tümmler
Journal: Journal of Clinical Investigation (1999)

Heterologous expression of the cystic fibrosis transmembrane conductance regulator (CFTR) provided evidence that the major cystic fibrosis (CF) mutation ΔF508 leads to defective protein folding in the endoplasmic reticulum, which prevents its processing and targeting to the cell surface. In this study, we investigated endogenous CFTR expression in skin biopsies and respiratory and intestinal tissue specimens from ΔF508 homozygous and non-CF patients, using immunohistochemical and immunoblot analyses with a panel of CFTR antibodies. CFTR expression was detected at the luminal surface of reabsorptive sweat ducts and airway submucosal glands, at the apex of ciliated cells in pseudostratified respiratory epithelia and of isolated cells of the villi of duodenum and jejunum, and within intracellular compartments of intestinal goblet cells. In ΔF508 homozygous patients, expression of the mutant protein proved to be tissue specific. Whereas ΔF508 CFTR was undetectable in sweat glands, the expression in the respiratory and intestinal tracts could not be distinguished from the wild-type by signal intensity or localization. The tissue-specific variation of ΔF508 CFTR expression from null to apparently normal amounts indicates that ΔF508 CFTR maturation can be modulated and suggests that determinants other than CFTR mislocalization should play a role in ΔF508 CF respiratory and intestinal disease.
A yellow bullet against the drivers of hepatic fibrogenesis
Authors: Ralf Weiskirchen, Frank Lammert
Journal: Hepatology (2008)

There are currently no approved antifibrotic therapies for liver cirrhosis. We used vitamin A-coupled liposomes to deliver small interfering RNA (siRNA) against gp46, the rat homolog of human heat shock protein 47, to hepatic stellate cells. Our approach exploits the key roles of these cells in both fibrogenesis as well as uptake and storage of vitamin A. Five treatments with the siRNA-bearing vitamin A-coupled liposomes almost completely resolved liver fibrosis and prolonged survival in rats with otherwise lethal dimethylnitrosamine-induced liver cirrhosis in a dose- and duration-dependent manner. Rescue was not related to off-target effects or associated with recruitment of innate immunity. Receptor-specific siRNA delivery was similarly effective in suppressing collagen secretion and treating fibrosis induced by CCl4 or bile duct ligation. The efficacy of the approach using both acute and chronic models of liver fibrosis suggests its therapeutic potential for reversing human liver cirrhosis.
Comment on Little et al. Recovery of Hypoglycemia Awareness in Long-standing Type 1 Diabetes: A Multicenter 2 × 2 Factorial Randomized Controlled Trial Comparing Insulin Pump With Multiple Daily Injections and Continuous With Conventional Glucose Self-monitoring (HypoCOMPaSS). Diabetes Care 2014;37:2114–2122
Authors: Steven V. Edelman
Journal: Diabetes Care (2014)

I appreciate the intent of the study by Little et al. (1) to determine whether hypoglycemia awareness can be improved and severe hypoglycemia prevented through rigorous avoidance of biochemical hypoglycemia. However, I am troubled by the methodology and conclusions.

The authors concluded that impaired awareness of hypoglycemia can be improved and recurrent severe hypoglycemia prevented in adults with long-standing type 1 diabetes through strategies deliverable in routine clinical practice. The care provided in the protocol could not be termed “routine” as none of the four study arms received conventional treatment. All arms received extensive interventions that included weekly contact, monthly follow-up visits, and …
Medical Man-power
Authors: D. M. O'Connor
Journal: BMJ (1941)

<h3>Abstract</h3> How cells tune the size of their subcellular parts to scale with cell size is a fundamental question in cell biology. Until now, most studies on the size control of organelles and other subcellular structures have focused on scaling relationships with cell volume, which can be explained by limiting pool mechanisms. Here, we uncover a distinct scaling relationship with cell length rather than volume, revealed by mathematical modeling and quantitative imaging of yeast actin cables. The extension rate of cables decelerates as they approach the rear of the cell, until cable length matches cell length. Further, the deceleration rate scales with cell length. These observations reveal a new mode of scaling that senses the linear dimensions of a cell. <h3>One Sentence Summary</h3> As actin cables in yeast cells grow longer, their extension rate decelerates, enabling the cable length to match cell length.
Comparison of assisted ventilator modes on triggering, patient effort, and dyspnea.
Authors: P Leung, A Jubran, M J Tobin
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

In 11 ventilator-dependent patients, we undertook a head-to-head comparison of patient-ventilator interaction during four ventilator modes: assist-control ventilation (ACV), intermittent mandatory ventilation (IMV), pressure support (PS), and a combination of IMV and PS. Progressive increases in IMV rate and PS level each decreased inspiratory pressure-time product (PTP) (p < 0.0001). These reductions in PTP were greater with PS than with IMV at lower but proportional levels of maximal assistance (p < 0.005). When PS 10 cm H2O was added to a given level of IMV, greater reductions in PTP were achieved not only during intervening (PS) breaths (p < 0.001), but also during mandatory (volume-assisted) breaths (p < 0.0005); this additional unloading during mandatory breaths was proportional to the decrease in respiratory drive (dP/dt) during intervening breaths (r = 0.67, p < 0.0001). Maximal unloading occurred with ACV, achieving more than a fivefold decrease in PTP compared with unassisted breathing. Decreases in PTP were confined to the post-trigger phase, and PTP of the post-trigger phase correlated with dP/dt (r = 0.78, p < 0.0001). Effort during the trigger phase remained constant despite marked changes in drive and intrinsic positive end-expiratory pressure (PEEPi). Ineffective triggering occurred with all modes, and wasted PTP increased with increasing levels of assistance as a result of the accompanying decrease in drive and increase in volume. Breaths preceding nontriggering efforts had shorter respiratory cycle times (p < 0.0005) and expiratory times (p < 0.0001) and higher PEEPi (p < 0.0001), indicating that neural-mechanical asynchrony resulted from inspiratory activity commencing prematurely before elastic recoil pressure had fallen to a level that could be overcome by a patient's muscular effort. Thus, increases in the level of ventilator assistance produced progressive decreases in inspiratory muscle effort and dyspnea,which were accompanied by increases in the rate of ineffective triggering.
What Should Be the Goal of Advance Care Planning?
Authors: Yael Schenker, Douglas B. White, Robert M. Arnold
Journal: JAMA Internal Medicine (2014)

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Genotoxicity of Escherichia coli Nissle 1917 strain cannot be dissociated from its probiotic activity
Authors: Maïwenn Olier, Ingrid Marcq, Christel Salvador-Cartier, Thomas Secher, Ulrich Dobrindt, Michèle Boury, Valérie Bacquié, Marie Penary, Eric Gaultier, Jean-Philippe Nougayrède, Jean Fioramonti, Eric Oswald
Journal: Gut Microbes (2012)

Oral administration of the probiotic bacterium Escherichia coli Nissle 1917 improves chronic inflammatory bowel diseases, but the molecular basis for this therapeutic efficacy is unknown. E. coli Nissle 1917 harbors a cluster of genes coding for the biosynthesis of hybrid nonribosomal peptide-polyketide(s). This biosynthetic pathway confers the ability for bacteria to induce DNA double strand breaks in eukaryotic cells. Here we reveal that inactivation of the clbA gene within this genomic island abrogated the ability for the strain to induce DNA damage and chromosomal abnormalities in non-transformed cultured rat intestinal epithelial cells but is required for the probiotic activity of E. coli Nissle 1917. Thus, evaluation of colitis severity induced in rodent fed with E. coli Nissle 1917 or an isogenic non-genotoxic mutant demonstrated the need for a functional biosynthetic pathway both in the amelioration of the disease and in the modulation of cytokine expression. Feeding rodents with a complemented strain for which genotoxicity was restored confirmed that this biosynthetic pathway contributes to the health benefits of the probiotic by modulating its immunomodulatory properties. Our data provide additional evidence for the benefit of this currently used probiotic in colitis but remind us that an efficient probiotic may also have side effects as any other medication.
Cystine Crystals in Fanconi's Syndrome
Authors: J K Singh, M F Kusior
Journal: New England Journal of Medicine (1999)

Figure 1. A 37-year-old man died of massive gastrointestinal bleeding from esophageal varices caused by biopsy-proved cirrhosis due to hepatitis C virus. He had been given a diagnosis of Fanconi's syndrome at the age of one year, when he presented with failure to thrive. The infantile form of cystinosis was diagnosed at the age of 13 years when a slit-lamp examination of the corneas, performed because of visual impairment, demonstrated cystine crystals. He was treated with sodium bicarbonate and vitamin D supplementation, but rickets developed. Despite receiving four renal transplants, the first at the age of 14 years, he had . . .
Alterations in peripheral hemodynamics in cirrhosis: are they related to methodology?
Authors: D. Sacerdoti, G.C. Bombonato, G.F. Finucci, A. Favaro, L. Spadaro, M. Bolognesi, E. Casiglia, L. Pavan, R. Biasin, G. Ginocchio, C. Onesto, A. Gatta
Journal: Journal of Hepatology (1998)
Premenstrual Exacerbations in Hepatic Porphyria: Prevention by Intermittent Administration of an LH-RH Agonist in Combination With a Gestagen
Authors: M. J. Bargetzi
Journal: JAMA (1989)

<h3>To the Editor.—</h3> Premenstrual attacks of hepatic porphyrias, in some cases occurring with each menstrual cycle, are well-known.<sup>1</sup>Anderson et al<sup>2</sup>in 1984 reported the potential benefit of use of a luteinizing hormone-releasing hormone (LH-RH) agonist in preventing premenstrual attacks. This result was confirmed by further case reports.<sup>3-5</sup>In all cases, the long-acting LH-RH agonist was administered continuously for months either subcutaneously or by nasal spray. We report one patient with cyclic exacerbations of acute intermittent porphyria and another patient with premenstrual exacerbations of variegate porphyria. In both patients, gynecologic evaluation revealed no abnormalities that could cause menstrual disorders. The attacks of neurological symptoms were prevented by the intermittent nasal administration of the long-acting LH-RH agonist buserelin in combination with the gestagen medroxyprogesterone acetate. The agonistic LH-RH analogue buserelin was given to both patients daily, with two hubs (2 × 150 μg) intranasally in the evening from
Basal C-Peptide in the Discrimination of Type I from Type II Diabetes
Authors: T A Welborn, P Garcia-Webb, Anne M Bonser
Journal: Diabetes Care (1981)

Basal serum C-peptide concentrations in diabetic patients showed two groups. Diabetic patients with low C-peptide levels (≤ 0.16 nmol/L) have clinical characteristics of type I diabetes, and all were on insulin therapy. With long duration of diabetes, an increasing proportion had undetectable C-peptide. Diabetic patients with high C-peptide levels (&amp;lt; 0.16 nmol/L) resemble type II diabetes. In this group 30% were on insulin therapy but duration of known disease was not associated with any decline in the high basal C-peptide levels. The small proportion of diabetic patients with basal serum C-peptide in the range of 0.17–0.32 nmol/L have indeterminate status.
Precipitins to Dietary Proteins in Serum and Upper Intestinal Secretions of Coeliac Children
Authors: A. Ferguson, F. Carswell
Journal: BMJ (1972)

We have used precipitin tests to detect antibodies to 10 dietary proteins in the serum (71 cases) and intestinal secretions (51 cases) of a group of children. Thirty-three of the patients had untreated coeliac disease. Our aims were to find out if, in coeliac patients, there was intestinal secretion of antibodies to wheat proteins only or if, as in coeliac serum, antibodies to many food proteins were present; and to confirm that secretion of antibodies to wheat or gluten was specific for coeliac disease.Precipitins to one or more dietary antigens were detected in the intestinal secretions of 26 out of 30 coeliacs and of 11 out of 21 children who did not have coeliac disease. Most of the positive reactions were with the antigens wheat flour, gluten, oatmeal, and egg. Though precipitins to wheat flour or gluten were present in the intestinal secretions of 22 out of 30 coeliacs this was not specific for coeliac disease for these precipitins were also present in 8 out of 21 non-coeliac children.Serum precipitins were detected in 27 out of 33 coeliacs (to the antigens wheat flour, gluten, oatmeal, rice flour, milk, bovine calf serum, sheep serum, and egg) and in 5 out of 33 non-coeliacs (mainly to milk and calf serum, but two infants aged 3 and 5 months had precipitins to several antigens).