tbuckley/cabot-search huggingface dataset:
Introduction of Single Base Substitutions at Homologous Chromosomal Sequences by Adeno-associated Virus Vectors
Authors: Naoki Inoue, Rong Dong, Roli K. Hirata, David W. Russell
Journal: Molecular Therapy (2001)

Adeno-associated virus (AAV) vectors can modify homologous chromosomal sequences at high rates. This gene targeting transduction pathway is distinct from the integrating and episomal pathways used in gene addition approaches. In previous studies, AAV vectors were used to introduce small insertion and deletion mutations at homologous chromosomal loci. Here we show that AAV-mediated gene targeting can also be used to introduce all possible types of single base substitution mutations at the endogenous single-copy hypoxanthine phosphoribosyl transferase locus. Southern blot and sequence analysis showed that the point mutations were introduced with high fidelity. We also show that AAV vectors can repair chromosomal alkaline phosphatase genes containing point mutations. Our results suggest that AAV vectors can be used to introduce single base substitutions at high frequencies in normal human cells, including the correction of point mutations responsible for genetic diseases.
Euthanasia and aiding suicide to remain criminal acts in Canada
Authors: B. Kermode-Scott
Journal: BMJ (2013)

Canada’s federal health minister has confirmed that there were no plans to change existing legislation so as to decriminalise euthanasia and doctor assisted suicide.

Rona Ambrose was responding to a Canadian Medical Association debate that exposed strong feelings among the country’s doctors on “mercy killing.”

She said, “Parliament voted in 2010 to not change its position on this issue. At this time we don’t have any intention of changing our position.”

Doctors revisited the topics of euthanasia, physician assisted suicide, and end of life care at the 146th …
Sulfur Colloid Distribution in Normal Hips
Authors: ARVIS G. WILLIAMS, FRED A. METTLER, JAMES H. CHRISTIE
Journal: Clinical Nuclear Medicine (1983)

The normal distribution of Tc-99m sulfur colloid is described in 100 patients with no clinical or radiographic evidence of hip disorders. Two-thirds of the patients had uptake in the femoral neck and some uptake in the femoral head. In the other one-third, no uptake was detected in either femoral head. A high degree of symmetry was noted. Judging both the symmetry and pattern of uptake in both hips is important in evaluating femoral head vasculature after a fracture.
Analgesia Inhaler for Trichlorethylene
Authors: H. G. Epstein, R. R. Macintosh
Journal: BMJ (1949)

BRITISH mucous membrane.A patch test to dentures was strongly positive.He was fitted with "plastic" dentures, and when seen again on March 7, 1949, the cracks had gone and the stomatitis was cured.Case 6.-A woman aged 39 came to the out-patient depart- ment on May 14, 1949, with an infected mole.Angular stoma- titis had been present for five and a half years; she had worn vulcanite dentures for about six years, and examination revealed the characteristic redness of the denture-contact area.A patch test when first tried was negative, but when repeated a delayed positive result was obtained.She was fitted with new teeth and the cracks have now healed.Case 7.-A woman aged 58, seen on July 30, 1949, had had cracks at the angles of the mouth for many years despite many different kinds of treatment.She has worn black vulcanite dentures for 35 years.The mucous membrane showed the characteristic appearance, and a patch test to the denture was strongly positive.She has now stopped wearing dentures and the condition is much better. CommentThese cases establish the association between denture sensitization and angular stomatitis.It is of interest that all these patients were in the habit of keeping their artificial teeth in at night, and it is reasonable to postulate that such a practice leads more readily to the establishment of a contact sensitization.In view of the numbers of dentures worn this condition is relatively uncommon, but in all the above cases the gum sensitivity was discovered only by direct questioning and examination, so that probably many cases are missed.
Ipswich Medical Society
Authors: C. M. Durrant
Journal: BMJ (1846)

A girl, aged 26, while in apparently good health, was suiddenly seized with apoplexy.CoIna, with dilated pupils obtained from the commencemnent, and she died in five hours.Bleeding was twice had recourse to without relief.Inspection.The nembranes as well as the substance of the brain were found injected, together with slight but general softening of the entire organ.A coagulum, weighing tbree ounce.s,was found lying beneath the pons Varolii, and extending into the fourtl ventricle.In the discussion upon this case, it was thought that in all probability chronic inflarnnation of the brain had existed for somle time previous to the attack, and that the ramollissenent was a precursor of the
KANK1, a candidate tumor suppressor gene, is fused to PDGFRB in an imatinib-responsive myeloid neoplasm with severe thrombocythemia
Authors: S Medves, F P Duhoux, A Ferrant, F Toffalini, G Ameye, J-M Libouton, H A Poirel, J-B Demoulin
Journal: Leukemia (2010)
Postoperative Complications of Intracranial Neurological Surgery
Authors: Walter Grand
Journal: JAMA (1983)

Drs Horwitz and Rizzoli are to be complimented for performing the monumental task of describing postoperative complications of intracranial surgery. In this volume, to be followed by a second volume delineating complications associated with spinal surgery, there is a comprehensive review of all aspects of complications relating to intracranial neurological surgery. The book covers the general complications accompanying intracranial surgery, including brain edema, postoperative hemorrhage, wound problems, and sepsis, as well as neurological deficits. The various aspects of complications are further categorized into intracranial neoplasms, aneurysms, arteriovenous malformations, head injuries, cranial operations for pain, intracranial infections, and congenital and acquired defects. Each chapter is excellently referenced and gives a historical background into various factors that affect mortality and morbidity in the various surgical procedures. This edition, which is a revision of a 1967 text, again is invaluable to the neurosurgical community. One must be aware that certain complications occur, so
GENERALIZED ANGIONEUROTIC EDEMA DUE TO PENICILLIN INHALATIONS TREATED WITH BENADRYL
Authors: DAVID SCHEINBERG
Journal: JAMA (1946)

There are accumulating cases in the literature of reactions to penicillin. These reactions have been on an allergic basis. They do not occur at once but only after the patient has had time to build up a sensitivity to the drug (or to the impurities in the drug). Obviously the reactions may follow any mode of medication. In this case the mode of administration of the drug was by nebulization into the lungs. J. D., a white man aged 54, has had chronic bronchitis and vasomotor rhinitis for many years. Upper respiratory infections have always aggravated his bronchitis. Mornings would bring an increase in cough and sputum, so that a diagnosis of bronchiectasis was entertained. X-ray examination of the lungs showed increased bronchial markings, but a bronchogram was not made. The past medical history revealed no attacks of asthma, no angioneurotic edema nor urticaria, no penicillin medication by any route.
Manifestaciones osteoarticulares de la Brucelosis
Authors: D. Preiskel
Journal: Annals of the Rheumatic Diseases (1959)

THE RHEUMATIC DISEASES pubis in 410 prostatectomies by taking special pre- cautions to prevent infected retropubic haematomata.In rare cases the intravertebral disks (about 3 months post-operatively), the hips (about 5 months post- operatively), and the tarsus could be involved by the same process.An example of the latter occurring 10
Prolonged biologically active transgene expression driven by HSV LAP2 in brain in vivo
Authors: Veljko Puskovic, Darren Wolfe, James Goss, Shaohua Huang, Marina Mata, Joseph C. Glorioso, David J. Fink
Journal: Molecular Therapy (2004)

Herpes simplex virus (HSV) naturally establishes a life-long latent state in neurons, characterized by the expression of latency-associated transcripts (LATs) in the absence of viral lytic functions, and the latency-associated promoter (LAP2) has been identified as a moveable element responsible for the expression of LATs from latent HSV genomes. Prolonged transgene expression will be required for the treatment of chronic diseases of the CNS using HSV vectors. We therefore examined the ability of LAP2 to drive prolonged expression of a biologically active transgene from latent HSV vector genomes in brain in vivo using the 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of Parkinson disease. A replication-incompetent HSV vector containing the glial cell-derived neurotrophic factor (GDNF) under the control of LAP2 was injected into the substantia nigra and 5 and a half months later 6-OHDA was injected into the striatum. GDNF expression from the vector preserved dopaminergic function measured by histology and behavior 6 months after vector inoculation. Mice inoculated with the LAP2-GDNF replication-incompetent HSV vector followed by 3 months of daily low-dose MPTP injections were substantially protected against the consequences of that treatment measured by weekly behavioral testing and histologic measures at the conclusion of the experiment. These studies using subacute and chronic models of neurodegeneration demonstrate that the HSV LAP2 promoter element provides prolonged expression of relevant amounts of a transgene to produce significant biological effects in brain in vivo over the course of many months.
Physicians and Health Policy
Authors: Matthew Menken
Journal: JAMA (1980)

To the Editor.—  I was delighted that JAMA published a physician's description of his midcareer health policy fellowship (243:1451, 1980), but I was disappointed by the limited scope of the accompanying editorial comment (243:1463, 1980). What is a fellowship all about anyway?  The impression I had was that the Johnson Foundation fellows use the year to get an overview of the complex machinations of government in the translation of health care policy concepts into practical pieces of legislation and sets of regulations. There is no mention of research, study, or scholarship—the traditional interpretation of fellowship—nor even a list of a dozen best-sellers that the fellows read to broaden their fund of information. By what standards shall the success of a fellowship program be measured, other than by self-fulfilling criteria such as the number of physician-fellows who subsequently pursue careers in policy? It would seem prudent that a fellowship program for
Solar urticaria: studies on mechanisms of tolerance
Authors: V. LEENUTAPHONG, E. HoLZLE, G. PLEWIG
Journal: British Journal of Dermatology (1990)

The mechanisms by which tolerance is induced in solar urticaria were investigated in two patients whose eruptions were induced by wavelengths in the range 320-455 nm in one patient and 400-495 nm in another. Tolerance to radiation was induced by repeated exposures of the skin to the eliciting wavelengths of light. Weal and flare responses to intradermal injections of histamine and the histamine-releasing agent (codeine) were unaltered in the tolerant skin when compared with adjacent normal skin. Intradermal injection of in vitro irradiated serum or plasma from the patients induced an urticarial reaction in the unexposed skin but not in tolerant skin and repeated injections induced tolerance to the eliciting radiation. The results suggest that tolerance is not due to exhaustion of the photoallergen in the skin, or to an increase of the mast-cell degranulation threshold caused by exposure to ultraviolet radiation, or mast-cell mediator depletion, or histamine tachyphylaxis. It is likely that binding sites of IgE on mast cells remain occupied by the photoallergen during the state of tolerance, and that histamine release from mast cells is blocked.
THE PERMANENT PRESERVATION OF ANATOMIC, EMBRYOLOGIC, PATHOLOGIC AND BACTERIOLOGIC SPECIMENS.
Authors: W. M. L. COPLIN
Journal: JAMA (1904)

In teaching by modern laboratory methods, nothing is more important than the artistic and accurate preservation of material in such a manner as to retain permanently the natural colors and secure mounts that conveniently can be labelled, handled and exhibited. The old methods, yielding uncolored, bulky masses, possessing, save in form, little resemblance to the original, gave most unsatisfactory results, and hence museums more than five or ten years of age no longer meet the requirements of to-day. The specimens I exhibited at the Atlantic City Session of the Association received such flattering notice, and so many have written for the details of the method, that it seems desirable to publish in full the various steps necessary to attain the results shown. Except in minor details (which are essential), the method makes no claim to originality; it is the assembling of what seemed the best in several methods, published and
AIDS and gay groups oppose Bush's nominee for surgeon general
Authors: Bob Roehr
Journal: BMJ (2007)

Officials in Nigeria have filed criminal and civil charges against Pfizer for its role in the deaths and disabilities of children who were treated with an experimental drug during a meningitis outbreak in Kano in 1996.The charges, filed by government prosecutors in Nigeria, follow three attempts by families of the children to sue in US courts.All three attempts were denied after Pfizer successfully argued that the US courts were not an appropriate forum.Four separate legal actions have been filed in Nigeria, including 31 criminal counts against 10 people, according to the Washington Post (www.washingtonpost.com, 2 Jun, "Pfizer faces new charges over Nigerian drug test").The plaintiffs also seek a total of $9bn (£4.5bn; €7bn) in civil suits.The charges stem from Pfizer's test of its unlicensed drug, trovafloxacin (Trovan) to treat 100 children with meningitis.A comparator group of 100 children were treated with a low dose of ceftriaxone.Suits on appeal in US courts charge Pfizer with causing harm to the children in both arms of the trial, alleging that a number of the children either died or were left deaf, mute, or brain damaged.The families allege that the company failed to tell them that their children were being enrolled in an experimental drug trial and that free, effective treatment was available from Médecins Sans Frontières at the same hospital.Five children in the trovafloxacin arm and six in the ceftriaxone arm died, according to Pfizer.Pfizer issued a statement in response to the charges, saying "Pfizer continues to emphasise-in the strongest terms-that the 1996 Trovan clinical study was conducted with the full knowledge of the Nigerian government and in a responsible and ethical way consistent with the company's abiding commitment to patient safety."Any allegations in these lawsuits to the contrary are simply untrue." Niger�ia files cr�iminal char�ges against Pfizer�
Cetuximab and Chemotherapy as Initial Treatment for Metastatic Colorectal Cancer
Authors: Eric Van Cutsem, Claus-Henning Köhne, Erika Hitre, Jerzy Zaluski, Chung-Rong Chang Chien, Anatoly Makhson, Geert D'Haens, Tamás Pintér, Robert Lim, György Bodoky, Jae Kyung Roh, Gunnar Folprecht, Paul Ruff, Christopher Stroh, Sabine Tejpar, Michael Schlichting, Johannes Nippgen, Philippe Rougier
Journal: New England Journal of Medicine (2009)

We investigated the efficacy of cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer and sought associations between the mutation status of the KRAS gene in tumors and clinical response to cetuximab.We randomly assigned patients with epidermal growth factor receptor-positive colorectal cancer with unresectable metastases to receive FOLFIRI either alone or in combination with cetuximab. The primary end point was progression-free survival.A total of 599 patients received cetuximab plus FOLFIRI, and 599 received FOLFIRI alone. The hazard ratio for progression-free survival in the cetuximab-FOLFIRI group as compared with the FOLFIRI group was 0.85 (95% confidence interval [CI], 0.72 to 0.99; P=0.048). There was no significant difference in the overall survival between the two treatment groups (hazard ratio, 0.93; 95% CI, 0.81 to 1.07; P=0.31). There was a significant interaction between treatment group and KRAS mutation status for tumor response (P=0.03) but not for progression-free survival (P=0.07) or overall survival (P=0.44). The hazard ratio for progression-free survival among patients with wild-type-KRAS tumors was 0.68 (95% CI, 0.50 to 0.94), in favor of the cetuximab-FOLFIRI group. The following grade 3 or 4 adverse events were more frequent with cetuximab plus FOLFIRI than with FOLFIRI alone: skin reactions (which were grade 3 only) (in 19.7% vs. 0.2% of patients, P<0.001), infusion-related reactions (in 2.5% vs. 0%, P<0.001), and diarrhea (in 15.7% vs. 10.5%, P=0.008).First-line treatment with cetuximab plus FOLFIRI, as compared with FOLFIRI alone, reduced the risk of progression of metastatic colorectal cancer. The benefit of cetuximab was limited to patients with KRAS wild-type tumors. (ClinicalTrials.gov number, NCT00154102.)
Acute effects of ibopamine on left ventricular mechanics in patients with idiopathic dilated cardiomyopathy
Authors: Giovanni Bellotti, Alvaro Moraes, Pedro Graziosi, Edimar Bocchi, Antonio Esteves, Caio Medeiros, Fernando Bacal, Giovanni Ceni, Fulvio Pieggi
Journal: Journal of the American College of Cardiology (1996)
Intimin type influences the site of human intestinal mucosal colonisation by enterohaemorrhagic Escherichia coli O157:H7
Authors: R J Fitzhenry, D J Pickard, Elizabeth Louise Hartland, S Reece, Godon Dougan, Alan D Phillips, Gad M Frankel
Journal: Gut (2002)

Background: Enterohaemorrhagic (EHEC) and enteropathogenic (EPEC) <i>Escherichia coli</i> epithelial cell adhesion is characterised by intimate attachment, and attaching and effacing (A/E) lesion formation. This event is mediated in part by intimin binding to another bacterial protein, Tir (translocated intimin receptor), which is exported by the bacteria and integrated into the host cell plasma membrane. Importantly, EPEC (O127:H6) and EHEC (O157:H7) express antigenically distinct intimin types known as intimin α and γ, respectively. EHEC (O157:H7) colonises human intestinal explants although adhesion is restricted to the follicle associated epithelium of Peyer9s patches. This phenotype is also observed with EPEC O127:H6 engineered to express EHEC intimin γ. Aims: To investigate the influence of intimin on colonisation of human intestine by <i>E coli</i> O157:H7, and intimin types on tissue tropism in humans. Methods: Human intestinal in vitro organ culture with wild type and mutant strains of O157:H7 were employed. Results: Introducing a deletion mutation in the <i>eae</i> gene encoding intimin γ in EHEC (O157:H7) caused the strain (ICC170) to fail to colonise human intestinal explants. However, colonisation of Peyer9s patches and A/E lesion formation were restored with intimin γ expression from a plasmid (ICC170 (pICC55)). In contrast, complementing the mutation with intimin α resulted in a strain (ICC170 (pCVD438)) capable of colonising and producing A/E lesions on both Peyer9s patch and other small intestinal explants. Conclusion: Intimin is necessary for human intestinal mucosal colonisation by <i>E coli</i> O157:H7. Intimin type influences the site of colonisation in a Tir type independent mechanism; intimin γ appears to restrict colonisation to human follicle associated epithelium.
Propranolol Prevents the Development of Heart Failure by Restoring FKBP12.6-Mediated Stabilization of Ryanodine Receptor
Authors: Masahiro Doi, Masafumi Yano, Shigeki Kobayashi, Masateru Kohno, Takahiro Tokuhisa, Shinichi Okuda, Masae Suetsugu, Yuhji Hisamatsu, Tomoko Ohkusa, Michihiro Kohno, Masunori Matsuzaki
Journal: Circulation (2002)

In heart failure, protein kinase A-mediated hyperphosphorylation of ryanodine receptors (RyRs) in sarcoplasmic reticulum (SR) causes dissociation of FKBP12.6 from RyRs. This results in an abnormal Ca2+ leak through RyRs, possibly leading to cardiac dysfunction. In the present study, we assess whether beta-blockers can correct this defect in RyR in tachycardia-induced heart failure and thereby improve cardiac function.SRs were isolated from dog left ventricular muscles (normal group, 4 weeks of rapid right ventricular pacing with or without propranolol [P(+) or P(-)]). End-diastolic and end-systolic diameters both increased less in P(+) than P(-), associated with a smaller decrease in fractional shortening in P(+). In SR from P(-), a prominent Ca2+ leak was observed, and FK506 (which dissociates FKBP12.6 from RyR) did not induce an additional Ca2+ leak. However, there was no appreciable Ca2+ leak in SR from P(+), although FK506 induced a Ca2+ leak as in normal SRs. In SR from P(+), an FK506-induced conformational change in RyR, which was virtually absent in SR from P(-), was observed as in normal SRs. Both the stoichiometry of FKBP12.6 versus RyR, assessed by [3H]FK506 and [3H]ryanodine binding assays, and the protein expression of FKBP12.6, assessed by Western blot analysis, were restored by propranolol toward the levels seen in normal SRs.Low-dose propranolol corrects the defective interaction of FKBP12.6 with RyR (restoration of RyR conformational change and prevention of Ca2+ leak from RyR), apparently resulting in an attenuation of intracellular Ca2+ overload and hence preventing the development of left ventricular remodeling in heart failure.
Parkin Disease
Authors: Karen M. Doherty, Laura Silveira-Moriyama, Laura Parkkinen, Daniel G. Healy, Michael Farrell, Niccolo E. Mencacci, Zeshan Ahmed, Francesca M. Brett, John Hardy, Niall Quinn, Timothy J. Counihan, Timothy Lynch, Zoe V. Fox, Tamas Revesz, Andrew J. Lees, Janice L. Holton
Journal: JAMA Neurology (2013)

Mutations in the gene encoding parkin (PARK2) are the most common cause of autosomal recessive juvenile-onset and young-onset parkinsonism. The few available detailed neuropathologic reports suggest that homozygous and compound heterozygous parkin mutations are characterized by severe substantia nigra pars compacta neuronal loss.
Characteristic purpura of the ears, vasculitis, and neutropenia–a potential public health epidemic associated with levamisole-adulterated cocaine
Authors: Catherine Chung, Paul C. Tumeh, Ron Birnbaum, Belinda H. Tan, Linda Sharp, Erin McCoy, Mary Gail Mercurio, Noah Craft
Journal: Journal of the American Academy of Dermatology (2011)
Hepatitis C virus antibodies and Graves' disease
Authors: O. Leri, M. T. Sinopoli, M. A. Di Prima, A. Di Prima
Journal: BMJ (1995)

Catholic beliefs about contraceptionEDrroR,-Gerard J Murphy presents Catholic belief about contraception.'However, the argument against contraception-that sex should be for pleasure and procreation, not for pleasure aloneapplies equally against sex during the "safe period" and sex with a pregnant or lactating partner.
Oxygen‐induced marrow red cell hypoplasia leading to transfusion in sickle painful crisis
Authors: Philip K. Lane, Stephen H. Embury, Pearl T. C. Y. Toy
Journal: American Journal of Hematology (1988)

Abstract The benefit of oxygen (O 2 ) therapy in non‐hypoxic sickle cell patients in painful crisis is uncertain. We report a case of a non‐hypoxic sickle cell patient in painful crisis who developed marrow red cell hypoplasia requiring transfusion support after O 2 therapy. The uncertain benefits of O 2 use in such cases must be weighed against the serious and underrecognized risks of transfusion. In patients who develop O 2 ‐induced marrow red cell hypoplasia, cessation of O 2 therapy may reverse the anemia and obviate the need for transfusion.