tbuckley/cabot-search huggingface dataset:
811. Correction of Laminin-5 β3 Chain Deficiency in Human Epidermal Stem Cells by Transcriptionally Targeted Lentiviral Vectors
Authors: Francesca Di Nunzio, Giulietta Maruggi, Stefano Ferrari, Marcela del Rio, Fernando Larcher, Michele De Luca, Fulvio Mavilio
Journal: Molecular Therapy (2006)

Mutations in any of the genes encoding the laminin 5 heterotrimer (α3, β3 and γ2) cause junctional epidermolysis bullosa (JEB), a severe and often fatal skin adhesion defect. We and others have shown that expression of a retrovirally transferred β3-chain cDNA in keratinocytes from affected patients reconstitutes normal synthesis, assembly and secretion of laminin 5, and corrects the adhesion defect in vitro and in vivo. We have recently started a phase-I clinical trial of gene therapy of JEB based on transplantation of cultured skin derived from autologous epidermal stem cells transduced with a MLV-derived retroviral vector. Since gamma- retroviral vectors have raised safety concerns for the genotoxic risk associated with the insertion of LTR elements into the human genome, we developed an alternative gene transfer strategy based on LTR- modified, HIV-derived lentiviral vectors. Two self-inactivating (SIN) lentiviral vectors were built, in which expression of either GFP or a LAMB3 cDNA is under the control of either a constitutive promoter (PGK) or the keratinocyte-specific, 2.2-kb promoter-enhancer of keratin 14 (K14). In a third construct, expression of the transgene is under the control of the viral LTR, modified by replacing the U3 region with two K14 enhancer elements. Analysis in human keratinocyte cultures and in full-thickness human skin equivalents reconstituted onto immunodeficient mice showed that GFP expression directed by the K14 elements is tissue-specific and restricted to the basal layer of the epidermis. Expression of laminin5 from the three alternative vectors was evaluated in keratinocyte cultures derived from skin biopsies of JEB patients. Biochemical and cell kinetics assays demonstrated transduction of epidermal clonogenic stem/progenitor cells and full phenotypic correction of JEB keratinocytes with all vectors. Southern blot analysis of individual cell clones showed that LTR-modified lentiviral vectors are genetically stable and integrate in multiple copies in the human genome. This study shows that the use of lentiviral vectors transcriptionally targeted to the basal keratinocytes by the insertion of restricted enhancer elements is an effective, and potentially safer, alternative for gene therapy of JEB.
Prevalence of known diabetes in Asians and Europeans.
Authors: H M Mather, H Keen
Journal: BMJ (1986)

In conclusion, no single technique for measuring microvascular perfusion answers all the questions.We do believe, however, that the technique of laser Doppler flowmetry applied with due regard to the anatomy and physiology of the skin represents an important tool for clinical research.It is far better validated as a measure of superficial microvascular volume flow rate than its predecessor, photoelectric plethysmography.
Personalized Chemotherapy Profiling Using Cancer Cell Lines from Selectable Mice
Authors: Hirohiko Kamiyama, Sherri Rauenzahn, Joong Sup Shim, Collins A. Karikari, Georg Feldmann, Li Hua, Mihoko Kamiyama, F. William Schuler, Ming-Tseh Lin, Robert M. Beaty, Balasubramanyam Karanam, Hong Liang, Michael E. Mullendore, Guanglan Mo, Manuel Hidalgo, Elizabeth Jaffee, Ralph H. Hruban, H.A. Jinnah, Richard B.S. Roden, Antonio Jimeno, Jun O. Liu, Anirban Maitra, James R. Eshleman
Journal: Clinical Cancer Research (2013)

Abstract Purpose: High-throughput chemosensitivity testing of low-passage cancer cell lines can be used to prioritize agents for personalized chemotherapy. However, generating cell lines from primary cancers is difficult because contaminating stromal cells overgrow the malignant cells. Experimental Design: We produced a series of hypoxanthine phosphoribosyl transferase (hprt)-null immunodeficient mice. During growth of human cancers in these mice, hprt-null murine stromal cells replace their human counterparts. Results: Pancreatic and ovarian cancers explanted from these mice were grown in selection media to produce pure human cancer cell lines. We screened one cell line with a 3,131-drug panel and identified 77 U.S. Food and Drug Administration (FDA)–approved drugs with activity, and two novel drugs to which the cell line was uniquely sensitive. Xenografts of this carcinoma were selectively responsive to both drugs. Conclusion: Chemotherapy can be personalized using patient-specific cell lines derived in biochemically selectable mice. Clin Cancer Res; 19(5); 1139–46. ©2012 AACR.
Differing acute phase responses in Crohn's disease and ulcerative colitis.
Authors: S H Saverymuttu, H J Hodgson, V S Chadwick, M B Pepys
Journal: Gut (1986)

Thirty eight patients with Crohn9s disease and 30 patients with ulcerative colitis have been assessed using the technique of faecal excretion of 111Indium granulocytes to quantify precisely acute inflammatory activity. At the time of each faecal granulocyte measurement the serum concentration of the acute phase protein C-reactive protein and the erythrocyte sedimentation rate were estimated. C-reactive protein concentration was significantly higher in Crohn9s disease than ulcerative colitis both overall and particularly in relation to given levels of granulocyte excretion. No such distinction was observed between the erythrocyte sedimentation rates in the two diseases. The present findings show that the acute phase response differs significantly between Crohn9s disease and ulcerative colitis. Patients with ulcerative colitis may be constitutionally different from those with Crohn9s disease and unable to mount a major acute phase response to their own disease.
Association of Heparin-Resistant Thrombin Activity With Acute Ischemic Complications of Coronary Interventions
Authors: Luigi Oltrona, Paul R. Eisenberg, John M. Lasala, David J. Sewall, Marc E. Shelton, Kenneth J. Winters
Journal: Circulation (1996)

Background Acute thrombosis is thought to contribute to abrupt coronary occlusion during percutaneous coronary revascularization despite the administration of heparin and aspirin. This study was designed to detect the presence of heparin-resistant thrombin activity and to define its relationship to the acute ischemic complications of coronary interventions. Methods and Results Plasma levels of fibrinopeptide A (FPA) and prothrombin fragment 1.2 (F1.2), markers of thrombin and factor Xa activity, respectively, were measured in the coronary sinus with heparin-bonded catheters in 58 patients undergoing coronary interventions. Activated coagulation times were maintained &gt;300 seconds by the Hemochron method. Mean FPA levels decreased significantly, from 7.0±0.9 nmol/L before the procedure to 5.2±0.5 nmol/L after the heparin bolus and to 2.9±0.2 nmol/L after the procedure ( P =.0001). In 26 patients (45%), FPA levels remained above the threshold for suppression of thrombin activity determined during angiography in 7 patients without coronary artery disease (&gt;3.0 nmol/L). FPA concentrations after coronary interventions were increased in patients with intracoronary thrombus ( P =.01), abrupt coronary occlusion ( P =.06), postprocedural non–Q-wave myocardial infarction ( P =.04), and clinically unsuccessful procedures ( P =.04). F1.2 levels were relatively low before the procedures and did not change significantly. Conclusions Heparin administration suppresses thrombin activity in most but not all patients undergoing coronary interventions. Heparin-resistant thrombin activity is associated with angiographic evidence of intracoronary thrombus and ischemic complications of coronary interventions.
Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: an angioscopic study
Authors: Masanori Asakura, Yasunori Ueda, Osamu Yamaguchi, Takayoshi Adachi, Atsushi Hirayama, Masatsugu Hori, Kazuhisa Kodama
Journal: Journal of the American College of Cardiology (2001)
Evaluation of a serological test for tuberculosis.
Authors: D A Mitchison, V R Aber, F J Ahmad, B W Allen, S Devi
Journal: BMJ (1977)

The agglutination test of Nicholls was found to be ineffective in diagnosing active tuberculosis. A positive result (titre of 1/125 or more) was found in the serum of 74 (70%) out of 105 patients with newly diagnosed, smear-positive pulmonary tuberculosis; 61 (62%) out of 98 healthy family contacts; and 19 (63%) out of 30 patients with non-tuberculous conditions. These findings were not due to faulty technique since the results obtained at Hammersmith were similar to those obtained by Nicholls's laboratory in the same serum samples. Twenty-seven of the tuberculous patients who had a negative result before treatment were retested two months after the start of chemotherapy but showed no evidence of a rising titre.
Successful treatment of cutaneous Langerhans cell histiocytosis with low-dose methotrexate.
Authors: A.E. Steen, K.H. Steen, R. Bauer, T. Bieber
Journal: British Journal of Dermatology (2001)

Langerhans cell histiocytosis (LCH) can be a difficult therapeutic problem. We present a 40-year-old woman with a 4-year history of LCH who was successfully treated with low-dose methotrexate (20 mg weekly).
Use of Cardiac Allografts With Mild and Moderate Left Ventricular Hypertrophy Can Be Safely Used in Heart Transplantation to Expand the Donor Pool
Authors: Sorel Goland, Lawrence S.C. Czer, Robert M. Kass, Robert J. Siegel, James Mirocha, Michele A. De Robertis, Jason Lee, Sharo Raissi, Wen Cheng, Gregory Fontana, Alfredo Trento
Journal: Journal of the American College of Cardiology (2008)
HOW TO IMPROVE THE CURRENT TREATMENT OF REFRACTORY CARDIOGENIC SHOCK: CLINICAL IMPACT OF EXTRACORPOREAL MEMBRANE OXYGENATION
Authors: Luisa Cacciavillani, Nicola Gasparetto, Vincenzo Tarzia, Martina Perazzolo Marra, Ervis Hiso, Armando Marzari, Gino Gerosa, Sabino Iliceto
Journal: Journal of the American College of Cardiology (2012)
Helicobacter pylori and Iron Deficiency
Authors: Helen Wood
Journal: JAMA (1997)

Gastric infection with<i>Helicobacter pylori</i>is common throughout the world. Usually acquired in childhood, this infection causes a chronic active gastritis. Chronic infection is usually asymptomatic, but its presence predisposes infected individuals to peptic ulcer disease.<sup>1</sup>Unlike gastropathies associated with nonsteroidal anti-inflammatory drugs (NSAIDs) or alcohol, which are erosive and hemorrhagic,<i>H pylori</i>gastritis is nonerosive and nonhemorrhagic,<sup>2</sup>the pathology of which is not visible through an endoscope. Thus,<i>H pylori</i>gastritis would not be considered a satisfactory explanation for chronic gastrointestinal blood loss or iron deficiency. However, in this issue, Yip et al<sup>3</sup>report in a cross-sectional study of Alaskan Yupik Eskimos (Yupiks) a high prevalence of See also p 1135. erosive-hemorrhagic gastritis, gastrointestinal bleeding, iron deficiency, and gastric<i>H pylori</i>infection. Is erosive-hemorrhagic gastritis with chronic gastric bleeding leading to iron deficiency another consequence of chronic<i>H pylori</i>infection? If so, is this manifestation unique
A Striking, Localized Eruption
Authors: Amanda J. Tschetter, Mary S. Stone, Marta J. VanBeek
Journal: JAMA Dermatology (2014)

A man in his 60s presented in consultation from his oncologist for a 3-week history of a pruritic eruption on his back in the setting of stage IV, progressive, neuroendocrine pancreatic cancer. He had undergone numerous chemotherapeutic regimens over the past 3 years, all of which had failed. For the past 4 months he had been receiving oral etoposide (daily for the first 3 weeks of each 4-week cycle), daily pancrelipase, and monthly octreotide acetate intramuscular injections. He denied the use of heating pads but admitted to sitting on the hearth, directly in front of his fireplace, for long periods because of the cold weather and chills presumably from his underlying malignant neoplasm. He acknowledged a mild, untreated seasonal rhinitis but otherwise had enjoyed good health prior to hiscancerdiagnosis.Physicalexaminationrevealeda large, reticulated,erythematousplaque withmicaceous and silvery scale localized to themid-back (Figure, A). A punch biopsywas performed (Figure, B-D). A B
Peroral endoscopic remyotomy for failed Heller myotomy: a prospective single-center study
Authors: P. Zhou, Q. Li, L. Yao, M. Xu, W. Chen, M. Cai, J. Hu, L. Li, Y. Zhang, Y. Zhong, L. Ma, W. Qin, Z. Cui
Journal: Endoscopy (2013)

Recurrence/persistence of symptoms occurs in approximately 20 % of patients after Heller myotomy for achalasia. Controversy exists regarding the therapy for patients in whom Heller myotomy has failed. The aim of the current study was to evaluate the efficacy and feasibility of peroral endoscopic myotomy (POEM), a new endoscopic myotomy technique, for patients with failed Heller myotomy.A total of 12 patients with recurrence/persistence of symptoms after Heller myotomy, as diagnosed by established methods and an Eckardt score of ≥ 4, were prospectively included. The primary outcome was symptom relief during follow-up, defined as an Eckardt score of ≤ 3. Secondary outcomes were procedure-related adverse events, lower esophageal sphincter (LES) pressure on manometry, reflux symptoms, and medication use before and after POEM.All 12 patients underwent successful POEM after a mean of 11.9 years (range 2 - 38 years) from the time of the primary Heller myotomy. No serious complications related to POEM were encountered. During a mean follow-up period of 10.4 months (range 5 - 14 months), treatment success was achieved in 11/12 patients (91.7 %; mean score pre- vs. post-treatment 9.2 vs. 1.3; P < 0.001). Mean LES pressure was 29.4 mmHg pre-treatment and 13.5 mmHg post-treatment (P < 0.001). One patient developed mild reflux symptoms and required intermittent medication with proton pump inhibitors.POEM seems to be a promising new treatment for failed Heller myotomy resulting in short-term symptom relief in > 90 % of cases. Previous Heller myotomy may make subsequent endoscopic remyotomy more challenging, but does not prevent successful POEM.
Diagnosis of stroke on neuroimaging
Authors: J M Wardlaw, A J Farrall
Journal: BMJ (2004)

“Scan all immediately” strategy improves outcomes and reduces costs 

Stroke is the clinical syndrome of rapid onset of focal, or sometimes global, cerebral deficit with a vascular cause, lasting more than 24 hours or leading to death.1 Eighty per cent of strokes are ischaemic, 15% are due to intracerebral haemorrhage, and 5% to subarachnoid haemorrhage. Correct diagnosis is important because treatments for ischaemic stroke2 may be contraindicated in intracerebral haemorrhage.3 The diagnosis requires imaging of the brain.4 But which imaging—computed tomography or magnetic resonance—how quickly should it be done, should this include imaging cerebral blood flow, and what is the most cost effective approach?

The average general hospital (catchment population 250 000-500 000) will see two to three patients with stroke per day. Many patients have poor airway control, are confused, or are unable to communicate. Routine imaging for most patients must therefore be quick (speed is of the essence for patients, salvaging their brain, and for the radiology department), practical, readily available, and yield the key diagnostic information. There is, however, no imaging technique that does all ofthese perfectly.

Computed tomography scanning is practical, quick (a few minutes to scan a brain), widely available, and easy to use in ill patients. It accurately identifies intracerebral haemorrhage as soon as it has occurred, but the technique has limitations. Intracerebral haemorrhage will be misinterpreted as ischaemic stroke if computed tomography is not done within 10-14 days after stroke.5 Delays in seeking medical …
Purification of the antigenic components of pigeon dropping extract, the responsible agent for cellular immunity in pigeon breeder’s disease
Authors: Kaoru Hisauchi-Kojima, Yuki Sumi, Yoshihiro Miyashita, Shuji Miyake, Hiroo Toyoda, Viswanath P. Kurup, Yasuyuki Yoshizawa
Journal: Journal of Allergy and Clinical Immunology (1999)
Friday the 13th and obsessive compulsive disorder
Authors: D. Veale
Journal: BMJ (1995)

Most readers of this journal are probably not superstitious. They are unlikely to change their behaviour this Friday the 13th despite a study showing significantly more road traffic accidents on Friday the 13th than Friday the 6th.1 They might, however, “touch wood” or choose a lucky number in the national lottery. People who are superstitious take it further. They see a causal relation between their own thoughts or actions and events in the world. Superstitions flourish whenever people cannot tolerate uncertainty or believe that they have no control over events; they lead us to believe that we can influence outcomes. Superstitiousness correlates significantly with the obsessional thoughts and compulsive checking experienced by people with obsessive compulsive disorder.2

Obsessive compulsive disorder consists of obsessions or compulsions or, most commonly, the two combined. Obsessions are recurrent intrusive thoughts, images, or urges that cause considerable anxiety or disgust. Typical obsessions concern contamination, misfortune, violence, blasphemy, and sex. Compulsions are thoughts or …
Fatty acid biosynthesis in human erythrocytes: evidence in mature erythrocytes for an incomplete long chain fatty acid synthesizing system.
Authors: J G Pittman, D B Martin
Journal: Journal of Clinical Investigation (1966)

immature mammalian and nucleated avian eryth- rocytes have been shown to possess the ability to synthesize long chain fatty acids from acetate, but this ability is apparently lost in the mature mammalian red cell (25)(26)(27)(28).The present study was undertaken to extend the information available on the mechanism of fatty acid synthesis in this readily accessible tissue and to define the metabolic lesion responsible for the reported inability of these cells to synthesize long chain fatty acids. MethodsPreparation of substrate.The following substrates, cofactors, and enzymes were purchased commercially: ATP,1 TPN,1 TPNH,1 DPNH,l glucose-6-phosphate dehydrogenase,1 coenzyme A,2 acetic acid-l-14C-anhydride,s bicarbonate->C,3 and malonic acid-2-14C.2Acetyl-CoA and acetyl-1-14C-CoA were synthesized by the method of Simon and Shemin (29) and malonyl-CoA and malonyl-2-14C-CoA by the method of Trams and Brady (30).Preparation of enzymes.Hemolysates were prepared from heparinized blood from normal, nonfasting, adult volunteers without regard to diet.All operations were carried out at 0 to 4°C.The erythrocytes were sepa-
Generic and disease‐specific quality of life as a predictor of long‐term mortality in heart failure
Authors: Maria Clemencia Zuluaga, Pilar Guallar‐Castillón, Esther López‐García, José R. Banegas, Manuel Conde‐Herrera, Maite Olcoz‐Chiva, Carlos Rodríguez‐Pascual, Fernando Rodriguez‐Artalejo
Journal: European Journal of Heart Failure (2010)
Role of clathrin- and caveolae-mediated endocytosis in gene transfer mediated by lipo- and polyplexes
Authors: Joanna Rejman, Alessandra Bragonzi, Massimo Conese
Journal: Molecular Therapy (2005)

We investigated the effects of inhibitors of clathrin-mediated endocytosis (chlorpromazine and K(+) depletion) and of caveolae-mediated uptake (filipin and genistein) on internalization of FITC-poly-l-lysine-labeled DOTAP/DNA lipoplexes and PEI/DNA polyplexes by A549 pneumocytes and HeLa cells and on the transfection efficiencies of these complexes with the luciferase gene. Uptake of the complexes was assayed by fluorescence-activated cell sorting. Lipoplex internalization was inhibited by chlorpromazine and K(+) depletion but unaffected by filipin and genistein. In contrast, polyplex internalization was inhibited by all four inhibitors. We conclude that lipoplex uptake proceeds only by clathrin-mediated endocytosis, while polyplexes are taken up by two mechanisms, one involving caveolae and the other clathrin-coated pits. Transfection by lipoplexes was entirely abolished by blocking clathrin-mediated endocytosis, whereas inhibition of the caveolae pathway had no effect. By contrast, transfection mediated by polyplexes was completely blocked by genistein and filipin but was unaffected by inhibitors of clathrin-mediated endocytosis. Fluorescence colocalization studies with a lysosomal marker, AlexaFluor-dextran, revealed that polyplexes taken up by clathrin-mediated endocytosis are targeted to the lysosomal compartment for degradation, while the polyplexes internalized via caveolae escape this compartment, permitting efficient transfection.
A novel way to prevent tension pneumothorax
Authors: W K C Morgan
Journal: BMJ (2004)

In October 1956 I was serving with the Royal Army Medical Corps at Connaught Military Hospital in Aldershot. This had been the Canadian hospital for the wounded from the second world war, but after the war the RAMC took it over. It became a chest hospital with several tuberculosis wards being occupied by military personnel or their families, along with some wards for other chest diseases.

One afternoon I was told to hurry to “Reception” to see a non-commissioned officer who had been shot during the Suez conflict and subsequently flown back home.

I was told that he had been shot in the chest …
The Changing Role of the Primary Physician and the Involvement oï the Professional Nurse in the Handling of Emotional Disorders
Authors: I. Frank, Rosanne K. Frank
Journal: Psychotherapy and Psychosomatics (1972)

The medical and nursing professions are having to formulate new patterns in patient care relationships. This is the result of the fact that larger numbers of patients are being seen with physiological symptoms which have their roots in emotional conflict. The primary purveyors of health care must, therefore, understand not only the physical, but also the psychological, socio-cultural, and economic aspects of his patients problems. This primary health care team of physician and nurse must be prepared to cope with the many emotional disorders which are the concomitants of physical illness. The team approach lends itself to greater flexibility in the management of the patient with psychosomatic illness.
Adrenocortical Hyperfunction in Association with Anaplastic Carcinoma of the Respiratory Tract
Authors: Paul Bornstein, James P. Nolan, David Bernanke
Journal: New England Journal of Medicine (1961)

THE association of hyperadrenocorticism with cancer has stimulated the curiosity of physicians for many years. Early work by Dobriner1 suggested that the adrenal glands functioned differently both qualitatively and quantitatively in patients with neoplastic disease. He proposed that the steroid metabolite 11-hydroxyetiocholanolone might actually be used to diagnose the existence of a neoplasm. These findings have not been confirmed.Previously, isolated case reports had recorded the association of a syndrome similar to Cushing's disease, with tumors in various organs, particularly in the pancreas,2 , 3 ovary4 , 5 and thymus.6 , 7 Similar findings have more recently been reported by Moore and his associates8 and Lockwood . . .
MPs call on health minister to halt closure of hospital for personality disorders
Authors: Susan Mayor
Journal: BMJ (2008)

MPs have called on the UK government to prevent the closure of a leading centre for people with personality disorder in a debate last week that highlighted the problems of shifting funding for specialist services to primary care trusts.

The Henderson Hospital, in Sutton, Surrey, is due to close in March because the South West London and St George’s Mental Health NHS Trust said it could no longer afford to subsidise the hospital, which provides intensive residential group therapy for adults with personality disorder.

Paul Burstow, MP for Sutton and Cheam, warned, “Unless the minister acts, the NHS is in danger of sleepwalking into the closure of this nationally and internationally renowned service.” Speaking during an adjournment debate in the House of Commons, he said that the hospital, …