tbuckley/cabot-search huggingface dataset:
Coronary vein grafting: the flags keep waving but the game goes on
Authors: A. C. Newby
Journal: Cardiovascular Research (2012)

This editorial refers to ‘Complement factor C5a as mast cell activator mediates vascular remodelling in vein graft disease’ by M.R. de Vries et al ., doi:10.1093/cvr/cvs312. 

Coronary artery bypass grafting came into practice in the 1960s and had grown to become the most widely performed surgical procedure with more than a million cases worldwide in 2010.1 In 1984, Claude Grondin,2 in an allusion to the rules of American football, threw a flag on the field of play and asked whether it was wise to continue using reversed saphenous vein as a bypass conduit, given that 10-year patency rates were as low as 50%.2 These concerns led to increased use of arterial conduits and also set in train almost three decades of investigation into the biology of vein graft failure, which continues in the study performed by de Vries et al .3 published in the current issue of Cardiovascular Research . From clinical and experimental results, early (days to weeks) thrombosis was found to occlude ∼10% of grafts as a result of endothelial injury during surgery. Subsequent medial and intimal thickening of the grafts was found to occur universally to adapt to arterial pressure and this resulted from migration and proliferation of vascular smooth muscle cells.1 There was also an inflammatory reaction to surgical implantation that included neutrophil and later macrophage infiltration and, as now shown,3 mast cells, too. The duration of these events in humans is of the order of several months. In 10% or so of grafts, over-exuberance …
The effect of epidermal growth factor (EGF) conjugated with low-molecular-weight protamine (LMWP) on wound healing of the skin
Authors: Jin Kyu Choi, Ji-Hye Jang, Won-Hee Jang, Jaekwan Kim, Il-Hong Bae, Joonho Bae, Young-Ho Park, Beum Joon Kim, Kyung-Min Lim, Jin Woo Park
Journal: Biomaterials (2012)
Origin of urinary nonconjugated 19-nor-deoxycorticosterone and metabolism of infused radiolabeled 19-nor-deoxycorticosterone in men and women.
Authors: M L Casey, A Guerami, L Milewich, C E Gomez-Sanchez, P C MacDonald
Journal: Journal of Clinical Investigation (1985)

It is known that 19-nor-deoxycorticosterone (19-nor-DOC) is a potent mineralocorticosteroid that is present in urine of rats and humans in a free, i.e., nonconjugated, form. In some forms of hypertension in rats, the levels of free 19-nor-DOC in urine are increased compared with those in urine of normotensive animals. Yet, despite the potential importance of this mineralocorticosteroid in the pathogenesis of certain forms of hypertension, little is known of its site of origin or metabolism. In the present investigation, we evaluated the metabolism of intravenously infused [3H]19-nor-DOC and the possibility that 19-nor-DOC was formed from plasma DOC. We found that the metabolism of [3H]19-nor-DOC infused intravenously in men and women was similar to that of DOC with important exceptions. The majority of the radiolabeled urinary metabolites of intravenously infused [3H]19-nor-DOC were excreted in urine as glucuronosides. Little radioactivity, infused as [3H]19-nor-DOC, was recovered in urine as nonconjugated or sulfoconjugated steroids. There was no free radiolabeled 19-nor-DOC in urine after the simultaneous infusion of [3H]19-nor-DOC and [14C]DOC. A major metabolite of [3H]19-nor-DOC in urine was 19-nor-DOC-21-glucuronoside, whereas little or no intravenously infused radiolabeled DOC was excreted as radiolabeled DOC-glucuronoside. We also found that intravenously infused [14C]DOC was not converted to urinary [14C]19-nor-DOC (glucuronoside) and that other tritium-labeled metabolites of infused [3H]19-nor-DOC contained no carbon-14. The production rate of 19-nor-DOC, computed from the specific activity of urinary 19-nor-DOC (glucuronoside), in one normal man was 16 micrograms/d and in the two women of this study, it was 10 micrograms/d. These findings are supportive of the proposition that free urinary 19-nor-DOC is not formed from plasma DOC; it may be formed in kidney from a precursor other than DOC or it may be formed nonenzymatically in kidney or urine from a precursor such as 19-oic-DOC.
Physical exercise conditioning in the absence of weight loss reduces fasting and postprandial triglyceride-rich lipoprotein levels.
Authors: M S Weintraub, Y Rosen, R Otto, S Eisenberg, J L Breslow
Journal: Circulation (1989)

The effect of physical exercise conditioning on fasting and postprandial lipoprotein levels was studied in six normolipidemic subjects. The study consisted of two phases: a baseline stabilization phase in which subjects maintained their regular physical activity and an exercise conditioning phase in which subjects had 29 exercise sessions during a 7-week period. Each of these sessions consisted of jogging on a treadmill for 30 minutes. The subjects averaged 15.2 miles/wk. To control for possible confounding factors, such as changes in diet composition and weight loss, we placed the subjects on a metabolic diet and increased their daily caloric intake during the exercise phase. At the end of each phase of the study, a vitamin A-fat loading test was done to specifically label and follow postprandial lipoprotein levels, and a maximum oxygen consumption test was done to evaluate the subjects' physical fitness. The exercise conditioning phase significantly increased the subjects' aerobic capacity and postheparin lipoprotein lipase activity, and the phase decreased fasting triglyceride levels. Physical exercise also significantly decreased chylomicron (Sf greater than 1,000) levels by 37%. In summary, this study suggests that physical exercise conditioning reduces fasting and postprandial lipoprotein levels by increasing the catabolism of triglyceride-rich particles. Because these particles may have a role in atherogenesis, this could be a major mechanism by which exercise prevents coronary heart disease.
10. Adeno-Associated Virus Type-1 Vectors Transduce Human Polarized Airway Epithelia without Polarity Preference
Authors: Ziying Yan, Diana C.M. Lei-Butters, Xiaoming Liu, Yulong Zhang, Meihui Luo, Liang Zhang, Roman Zak, John F. Engelhardt
Journal: Molecular Therapy (2006)

The choice of appropriate adeno-associated virus serotypes for gene therapy to the human lung can differ depending on the animal model and model system in which such serotypes are evaluated. In the present study, we sought to compare the efficiency of rAAV2/1, rAAV2/2, and rAAV2/5 vector transduction in polarized human airway epithelia. Since similar vector purity is paramount to such a comparison, we developed a uniform procedure for purification of these serotype vectors using an adenovirus-free packaging system and HPLC. Results from these experiments demonstrated that apical transduction of human polarized airway epithelia with rAAV2/1 was 100-fold more efficient than rAAV2/2 and rAAV2/5. Additionally, the profile of apical transduction in human airway epithelia (rAAV2/1>>rAAV2/2=rAAV2/5) was significantly different than that seen following nasal administration of these vectors to mouse lung (rAAV2/5>rAAV2/1>>rAAV2/2), emphasizing differences in transduction of these serotypes between these two species. In stark contrast to rAAV2/2 and rAAV2/5 vectors, which demonstrated much greater transduction efficiencies from the basolateral membranes, rAAV2/1 transduced both apical and basolateral membrane of human airway epithelia with similar efficiency. Such serotype-specific difference in apical and basolateral transduction mirrored differences in internalization of vector genomes at short time points post-infection for a given serotype. However, the overall level of transduction across serotypes did not correlate with vector internalization. These results suggested that enhanced receptor-mediated endocytosis was not likely responsible for the greater rAAV2/1 transduction of human airway epithelia. With the hypothesis that differences in post-entry barriers influenced the efficiency of apical transduction with these three serotypes in the human airway, we tested the effectiveness of proteasome inhibitors (LLnL and doxorubicin, known to augment intracellular processing of rAAV2 and rAAV5 to the nucleus) to augment transduction with these three serotypes. Augmentation of rAAV2/1 apical transduction of human polarized airway epithelia was 10-fold lower than that for rAAV2/2 and rAAV2/5. Cellular fractionation assays demonstrated that proteasome inhibitors significantly increased virion nuclear uptake for rAAV2/2 and rAAV2/5, but not for rAAV2/1. Cumulatively, these findings suggest that the ubiquitin/proteasome pathway is less of a barrier for rAAV2/1 as compared to the other AAV serotypes. They also demonstrate that AAV1 serotype transduction biology is quite different from AAV2 and AAV5 in human airway epithelia and is potentially a more efficient vector for gene therapy to the airway.
Blockade of Nitric Oxide Synthesis Reduces Myocardial Oxygen Consumption In Vivo
Authors: Andrew J. Sherman, Cornelius A. Davis, Francis J. Klocke, Kathleen R. Harris, Gopalakrishnan Srinivasan, Adel S. Yaacoub, Debra A. Quinn, KaLee A. Ahlin, James J. Jang
Journal: Circulation (1997)

Background Although cardiac myocytes and coronary vascular endothelium are known to express a constitutive form of NO synthase, the in vivo effects of tonic endogenous production of NO on myocardial O 2 consumption and contractile performance remain unclear. Methods and Results The effects of blockade of NO synthase were determined in intact dogs. Myocardial O 2 consumption decreased systematically over a wide range of hemodynamic demand after the systemic administration of N ω -nitro- l -arginine methyl ester (L-NAME) or N ω -nitro- l -arginine. Decreases after doses of 1 and 10 mg/kg L-NAME averaged 23±3.8% and 34±7.2% at a heart rate of 90 bpm in open-chest animals. Similar reductions occurred after the administration of L-NAME and N ω -nitro- l -arginine in chronically instrumented animals and were unaffected by β-adrenergic blockade. Intracoronary infusion of L-NAME in chronically instrumented animals reduced both myocardial O 2 consumption and regional segment shortening, even at a dose that did not increase systemic arterial pressure. Conclusions The blockade of NO synthesis reduces myocardial O 2 consumption in vivo. The decrease in O 2 consumption is accompanied by a decrease in segment shortening. It involves a direct myocardial action of NO, is unaffected by β-blockade, and is consistent with in vitro studies indicating that low levels of NO augment contractile performance by inhibition of a cGMP-dependent phosphodiesterase.
The Parenteral Use of Vitamin Preparations
Authors: Franz J. Ingelfinger
Journal: New England Journal of Medicine (1945)

NiacinNiacin (nicotinic acid)* is another water-soluble member of the vitamin B complex. In whole blood, its concentration varies between 0.3 and 0.9 mg. per 100 cc, 90 per cent of this amount being present in the corpuscles as a constituent of co-enzymes I and II.71 72 73 The plasma content of niacin, apparently in the free form, ranges between 0.05 and 0.24 mg. per 100 cc.72 , 73 When niacin is injected, its amide (nicotinamide, niacin amide) should be used to avoid the distressing flushing reactions that attend the parenteral administration of niacin itself. The injection of large doses of nicotinamide intravenously or . . .
Liquor Adulterated with Lye as a Cause of Dysphagia and Stricture of the Esophagus
Authors: U. K. Kiviranta
Journal: New England Journal of Medicine (1950)

IN THE literature on corrosion and stricture of the esophagus I remember reading about an alcoholic patient who for years had been in the habit of drinking whisky straight and who finally cast up the whole wall of his esophagus. Now and then, casting up of "Ausgusse" of the esophagus happens specifically in patients with lye corrosion one to three weeks after the accident. In the case described above the phenomenon was explained as being due to use of too-concentrated alcohol. I have never observed anyone to have paid attention to the following possible cause of corrosion.The Finnish man . . .
Allogeneic carrier-specific enhancement of hapten-specific secondary B-cell responses.
Authors: S K Pierce, N R Klinman
Journal: The Journal of Experimental Medicine (1976)

We have analyzed the capacity of carrier-specific T cells to enhance the immune response of hapten-specific secondary B cells which do not share genes in the H-2 complex with the T cells. For this analysis we have used the in vitro splenic focus technique which allows assessment of monoclonal responses of B cells isolated in splenic fragment cultures of irradiated reconstituted carrier primed mice. A previous report from this laboratory demonstrated that syngeny in the I region of the H-2 complex was necessary between collaborating hapten-specific primary (nonimmune) B cells and carrier-specific T cells for responses yielding IgG1 but not IgM antibody. These findings lead up to postulate that the expression of I-region gene products on the surface of primary B cells and I-region syngeny with collaborating carrier-specific T cells were essential elements in the triggering events leading to IgG1 synthesis by primary B cells. The results presented in the present report indicate that, unlike primary B cells, the majority of secondary B cells can be stimulated to produce IgG1 antibody in carrier-primed allogeneic recipients. Although the enhancement of secondary IgG1 responses is slightly greater with syngeneic T cells, the allogeneic collaborative interaction requires both carrier priming of recipient mice and stimulation with the homologous hapten-carrier complex and thus appears to be specific. These findings clearly discriminate secondary from primary B cells and indicate that the mechanism of stimulation of secondary B cells to yield IgG1-producing clones differs fundamentally from the stimulation of primary B cells in that the requisite for I-region syngeny is obviated.
P62 Drug induced hypothyroidism in patients receiving treatment for multi-drug resistant tuberculosis
Authors: J. Gupta, R. A. M. Breen, H. J. Milburn
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Drug-induced hypothyroidism is an uncommon adverse effect of treatment for multi-drug resistant tuberculosis (MDR-TB), with a limited number of case reports from the 1950s reporting the issue. The most likely agents to cause hypothyroidism are <i>p</i>-aminosalicylic acid (PAS), and to a lesser extent Prothionamide, both commonly used in regimens to treat MDR-TB. We report five cases of MDR-TB, four of whom developed hypothyroidism while on treatment. This is the largest reported cohort to have developed drug-induced hypothyroidism as a result of MDR-TB treatment to date. We analysed if there were any predisposing or causative factors which may have contributed to patients developing hypothyroidism. <h3>Method</h3> Patients were seen in clinic on a regular basis and possible adverse events evaluated by symptom review and clinical evaluation. Thyroid function tests (TFTs) were ordered based upon clinical suspicion. Following identification of hypothyroidism patients were started on thyroxine replacement therapy with monitoring of TFT levels to normalise them. Patient demographics were collected for analysis. <h3>Results</h3> Four out of five patients (3 females and 1 male, aged 29–40 years) developed hypothyroidism following MDR-TB treatment with regimens containing PAS and Prothionamide. The dominant presenting symptom was lethargy, with one developing goitre and hair loss. All patients were from ethnic minorities born overseas in: India (1); Bangladesh (1) and Somalia (2). The 5<sup>th</sup> female Nepalese patient remained euthyroid. Patients had been in the UK from 3 to 6 years with no travel history of note since. Hypothyroidism developed at varying stages of treatment from 101–442 days. On analysis of predisposing or causative factors for hypothyroidism development, those patients who originated from areas of iodine deficiency (eg, Bangladesh) developed hypothyroidism sooner after commencing treatment and took longer for euthyroid resolution despite receiving increased dosages of thyroxine replacement therapy. <h3>Conclusion</h3> Individuals originating from areas of iodine deficiency have an increased likelihood of developing drug induced hypothyroidism when receiving a regimen containing PAS and/or Prothionamide for MDR-TB treatment. As symptoms of hypothyroidism were generally non-specific and could easily be ascribed to TB, we suggest monitoring TFTs in all patients on prolonged treatment regimens containing PAS and/or Prothionamide.
Interactions of non-ionic surfactant vesicles with cultured keratinocytes and human skin in vitro: a survey of toxicological aspects and ultrastructural changes in stratum corneum
Authors: H.E.J. Hofland, J.A. Bouwstra, M. Ponec, H.E. Boddé, F. Spies, J.Coos Verhoef, H.E. Junginger
Journal: Journal of Controlled Release (1991)
Comprehensive Genomic Analysis Reveals Clinically Relevant Molecular Distinctions between Thymic Carcinomas and Thymomas
Authors: Nicolas Girard, Ronglai Shen, Tianhua Guo, Maureen F. Zakowski, Adriana Heguy, Gregory J. Riely, James Huang, Christopher Lau, Alex E. Lash, Marc Ladanyi, Agnes Viale, Cristina R. Antonescu, William D. Travis, Valerie W. Rusch, Mark G. Kris, William Pao
Journal: Clinical Cancer Research (2009)

Thymomas and thymic carcinomas are rare intrathoracic malignancies that can be invasive and refractory to conventional treatment. Because these tumors both originate from the thymus, they are often grouped together clinically. However, whether the underlying biology of these tumors warrants such clustering is unclear, and the optimum treatment of either entity is unknown.All thymic tumors were profiled for mutations in genes encoding components of the EGFR and KIT signaling pathways, assessed for EGFR and KIT expression by immunohistochemistry, and analyzed by array-based comparative genomic hybridization. Previously untreated tumors were subjected to global gene expression arrays.We analyzed 45 thymic tumors [thymoma, n = 38 (type A, n = 8; type B2, n = 22; type B3, n = 8); thymic carcinoma, n = 7]. One thymoma and one thymic carcinoma harbored KRAS mutations (G12A and G12V, respectively), and one thymoma had a G13V HRAS mutation. Three tumors displayed strong KIT staining. Two thymic carcinomas harbored somatic KIT mutations (V560del and H697Y). In cell viability assays, the V560del mutant was associated with similar sensitivities to imatinib and sunitinib, whereas the H697Y mutant displayed greater sensitivity to sunitinib. Genomic profiling revealed distinct differences between type A to B2 thymomas versus type B3 and thymic carcinomas. Moreover, array-based comparative genomic hybridization could readily distinguish squamous cell carcinomas of the thymus versus the lung, which can often present a diagnostic challenge.Comprehensive genomic analysis suggests that thymic carcinomas are molecularly distinct from thymomas. These data have clinical, pathologic, and therapeutic implications for the treatment of thymic malignancies.
Scintigraphic Probability and Angiographic Diagnostic Certainty in Acute Pulmonary Embolism
Authors: Jean Lette, Michel Cerino, Gaetan Barrette, Michel-Pierre Dufresne, Stéphane De Maria, Marie-Claire Eybalin, André Levasseur
Journal: Clinical Nuclear Medicine (2003)

The objectives of this study were to determine if diagnostic certainty on angiography correlates with scintigraphic probability for the diagnosis of pulmonary embolism. From a total of 160 consecutive patients who underwent both nuclear imaging and invasive selective pulmonary angiography, we reviewed the xenon-133 ventilation images in 2 posterior oblique views and the Tc-99m macroaggregated serum albumin perfusion scans and angiograms of 40 patients (15 men, 25 women; average age 57 years) who were discharged from the hospital on anticoagulants with a diagnosis of pulmonary embolism. The angiograms were reviewed and the diagnosis of embolism was considered certain in the presence of an intraluminal filling defect, a trailing embolus, or a branch occlusion equal to or larger than a segmental branch (n = 29; 73%), and uncertain when the studies were reinterpreted as either equivocal or negative or in the presence of a single, small subsegmental filling defect of questionable clinical significance. The ventilation-perfusion scans were read as high (n = 18; 45%), intermediate (n = 10; 25%), or low (n = 12; 30%) probability. The proportion of patients with diagnostic certainty on angiography in the high-, intermediate-, and low-probability scintigraphic subgroups was, respectively, 100% (18 of 18), 70% (7 of 10), and 33% (4 of 12) (P = 0.004). In patients diagnosed with pulmonary embolism based on selective angiography, a lower probability of pulmonary embolism on ventilation-perfusion scintigraphy correlates with a lesser degree of diagnostic certainty on angiography and a higher incidence of single subsegmental emboli.
Permethrin Treatment of Head Lice with Knockdown Resistance–like Gene
Authors: Ralf Bialek, Ulrike E. Zelck, Regina Fölster-Holst
Journal: New England Journal of Medicine (2011)

To the Editor: Chosidow and colleagues (March 11, 2010, issue)1 justify their study of oral ivermectin for the treatment of pediculosis capitis by the increasing resistance of head lice to pyrethroids because of amino acid substitutions (Thr929Ile and Leu932Phe) in the alpha subunit of the voltage-gated sodium channel. These substitutions are considered to reduce or delay the insecticidal effects of permethrin and dichlorodiphenyltrichloroethane (DDT).2 The DNA sequence bearing the two mutations is called the knockdown resistance (kdr)–like gene, which has been detected in up to 95% of head lice examined in Europe.3,4 However, the gene has not been studied . . .
A monoclonal antibody recognizes a von Willebrand factor domain within the amino-terminal portion of the subunit that modulates the function of the glycoprotein IB- and IIB/IIIA-binding domains.
Authors: I Tornai, J Arnout, H Deckmyn, K Peerlinck, J Vermylen
Journal: Journal of Clinical Investigation (1993)

We developed a monoclonal antibody, 1C1E7, against vWf that increases ristocetin-induced platelet aggregation in a dose-dependent manner and lowers the threshold concentration of ristocetin needed to obtain a full aggregatory response. The platelet aggregatory effect of asialo vWf (ASvWf) also is enhanced by 1C1E7, in the presence or absence of glycoprotein (GP) IIb/IIIa receptor antagonism. In the presence of ristocetin, both intact 1C1E7 and its Fab fragments enhance specific binding of 125I-vWf to platelets. With 1C1E7, the intermediate and higher molecular weight multimers of vWf are preferentially bound to both GP Ib and GP IIb/IIIa. Thrombin-induced 125I-vWf binding to GP IIb/IIIa also is increased by 1C1E7. Maximal binding of 1C1E7 to vWf corresponds to 0.97 mol/mol vWf monomer with a Kd of 4.7 x 10(-10) M. 1C1E7 reacts with a 34/36-kD tryptic fragment (III-T4) and a 34-kD plasmic fragment (P34), which localizes the epitope between amino acid residues 1 and 272; this was confirmed by NH2-terminal amino acid sequencing. Finally, platelet aggregation by ASvWf was associated with a sharp rise in intracellular Ca2+ only in the presence of 1C1E7. An antibody-mediated conformational change of vWf may result in an improved presentation of the GP Ib- and GP IIb/IIIa-binding domains of mainly the larger multimers; the increased density of vWf on the platelet surface leads to platelet activation. The antibody may thus recognize a domain of relevance for vWf physiology.
Treating homosexuality as a sickness:Step in the right direction has been taken
Authors: Justin Varney
Journal: BMJ (2004)

EDITOR—Smith et al bring a new voice to a practice that had been hidden in the closet of medical history,1 and Lovitt is right to say that this openness may start a path to reconcile the psychiatric and gay populations (first letter). Some schools of psychotherapy, however, still view homosexuality as an aberration capable of cure, and several targeted religious programmes of intervention …