tbuckley/cabot-search huggingface dataset:
404. Therapeutic Correction of PKU in a Mouse Model by Ectopic Expression of PAH and Its BH4- Cofactor Genes in Skeletal Muscle by a Recombinant Triple-Cistronic AAV2-Based Pseudotype 1 Vector
Authors: Zhaobing Ding, Cary O. Harding, Alexandre Rebuffat, Lina Elzaouk, JonA. Wolff, Beat Thony
Journal: Molecular Therapy (2006)

Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism with a deficiency of the hepatic phenylalanine hydroxylase (PAH) leading to toxic accumulation of circulating phenylalanine (Phe) in blood, resulting in growth failure, microcephaly, seizures, and mental retardation. PAH catalyzes the hydroxylation of Phe to tyrosine and needs oxygen and tetrahydrobiopterin (BH4) as cofactor. BH4 biosynthesis requires the consecutive action of the enzymes GTPCH and PTPS, with dihydroneopterin triphosphate as the first intermediate. Here we aimed at expressing the PAH system in skeletal muscle to degrade serum Phe in PKU patients, as this tissue is abundant, easy accessible, and persistent due to its post-mitotic nuclei. However, BH4 is abundant in liver but scarce in skeletal muscle, as the cofactor- synthesizing enzyme GTPCH is absent in muscle tissue, and PTPS is expressed at low levels. We first demonstrated that transgenic PKU mice that had no liver PAH and expressed coordinately PAH along with GTPCH in skeletal muscle tissue accumulated dihydroneopterin triphosphate and remained hyperphenylalaninemic unless synthetic BH4-cofactor was supplied by intraperitoneal injections. Thus, PTPS activity is definitely limiting in skeletal muscle to synthesize sufficient BH4 and to support Phe hydroxylation. A recombinant triple-cistronic AAV2- based pseudotype 1 vector expressing PAH along with the two cDNA-genes for BH4 biosynthesis, GTPCH and PTPS, was then generated. Upon single injections of at least 3.5x10e12 recombinant triple-cistronic AAV2/1 vector particles into each of the gastrocnemius muscles of the hind legs of the PKU mouse model Pah-enu2 resulted in long-term clearance of blood Phe, including complete phenotypic reversion. A similar therapeutic effect was achieved when a combination of two AAV2/1 vectors expressing individually PAH and GTPCH-PTPS were co-injected into the same hind leg muscles. As a control, an AAV2/1-vector expressing only PAH with GTPCH was not therapeutic. This non-invasive application is the basis to develop an efficient therapy for PKU using a triple-cistronic gene transfer into skeletal muscle.
Truncal Vagotomy and Drainage for Chronic Duodenal Ulcer Disease: A Controlled Trial
Authors: F. Kennedy, C. MacKay, B. S. Bedi, A. W. Kay
Journal: BMJ (1973)

The results of elective truncal vagotomy and drainage in 547 duodenal ulcer patients are reported. Altogether, 204 patients were randomly allocated to pyloroplasty and 200 to gastrojejunostomy. In 101 patients gastrojejunostomy was electively chosen and in 42 patients the duodenum was opened to confirm the diagnosis. Operative mortality was 0·5%, the incidence of proved recurrent ulceration 3·3%, severe dumping 2%, and severe diarrhoea 1·1%. There were no significant differences between the groups, with the exception of bilious vomiting which occurred more often in patients with gastrojejunostomy.
Glutamate decarboxylase-, insulin-, and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children.
Authors: W A Hagopian, C B Sanjeevi, I Kockum, M Landin-Olsson, A E Karlsen, G Sundkvist, G Dahlquist, J Palmer, A Lernmark
Journal: Journal of Clinical Investigation (1995)

Most autoimmune diabetes occurs in those without a diabetic relative, but few cases are identifiable prospectively. To model general population prediction, 491 consecutive newly diabetic children from all of Sweden were tested for autoantibodies to glutamate decarboxylase (GAD65ab), insulin (IAA), and islet cells (ICA), and for HLA-DQ genotypes by PCR; 415 matched control children were tested in parallel. GAD65ab sensitivity/specificity was 70/96%, versus 84/96% for ICA, 56/97% for IAA, 93/93% (any positive), 39/99.7% (all positive), and 41/99.7% (GAD65ab plus IAA). The latter's 25% predictive value was not improved by requiring concomitant high-risk HLA genotypes. GAD65ab were associated with DQA1*0501/B1*0201 (DQ2; P = 0.007) but not DQA1*0301/B1*0302 (DQ8), and IAA with DQA1*0301/B1*0302 (DQ8; P = 0.03) but not DQA1*0501/B1*0201 (DQ2). GAD65ab were more prevalent in females than males (79 vs. 63%; P < 0.0001) but did not vary with onset age nor season. Combining the three antibody assays yielded sufficient sensitivity for screening. GADab were relatively sensitive/specific for diabetes, but even with HLA marker combinations yielded predictive values insufficient for early immunointervention in the low-prevalence general population.
Improving the health of the world's poor
Authors: D. R Gwatkin, P. Heuveline
Journal: BMJ (1997)

Several prominent reports have recently called attention to the world's health transition,1 2 3 4 5 a process associated with reductions in fertility and improvements in overall health. As the transition progresses death and disability among infants and children from communicable diseases tend to decline in importance relative to problems resulting from non-communicable conditions at older ages.

The transition has proceeded furthest in the developed countries, but it has also occurred in the developing world. Recognising this, many observers have begun thinking in terms of a double burden of disease in developing countries.6 7 The first is the “unfinished agenda” of communicable diseases in the young, which dominated professional thought in the decade after the World Health Organisation's 1978 Alma-Ata conference on primary health care. The second is the “emerging agenda” of non-communicable …
Health status and plasma dioxin levels in chloracne cases 20 years after the Seveso, Italy accident
Authors: A. Baccarelli, A.C. Pesatori, D. Consonni, P. Mocarelli, D.G. Patterson, N.E. Caporaso, P.A. Bertazzi, M.T. Landi
Journal: British Journal of Dermatology (2005)

Background The Seveso, Italy accident of 1976 exposed a large population to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or simply dioxin). The accident resulted, mostly among children, in one of the largest ever-reported outbreaks of chloracne, the typical skin disorder due to halogenated-hydrocarbon compounds. Objectives Approximately 20 years after the accident, we conducted an epidemiological study in Seveso to investigate (a) the health status of chloracne cases; (b) TCDD-chloracne exposure–response relationship; and (c) factors modifying TCDD toxicity. Methods From 1993 to 1998, we recruited 101 chloracne cases and 211 controls. Trained interviewers administered a structured questionnaire assessing, among other epidemiological variables, information on an extensive list of diseases. During the interview, individual pigmentary characteristics were determined. We measured plasma TCDD levels using high-resolution gas chromatography/mass spectrometry. Results Plasma TCDD was still elevated (> 10 ppt) in 78 (26·6%) of the 293 subjects with adequate plasma samples, particularly in females, in subjects who had eaten home-grown animals, and in individuals with older age, higher body mass index and residence near the accident site. After 20 years, health conditions of chloracne cases were similar to those of controls from the Seveso area. Elevated plasma TCDD was associated with chloracne [odds ratio (OR) = 3·7, 95% confidence interval (CI) 1·6–8·8, adjusted for age, sex and residence]. Chloracne risk was higher in subjects younger than 8 years at the accident (OR = 7·4, 95% CI 1·8–30·3) and, contrary to previous hypotheses, did not increase at puberty onset or in teenage years. Subjects with elevated TCDD levels and light hair colour had higher relative odds of chloracne (OR = 9·2, 95% CI 2·6–32·5). Conclusions Dioxin toxicity in chloracne cases was confined to the acute dermatotoxic effects. Chloracne occurrence appeared related to younger age and light hair colour. Age-related dioxin elimination or dilution must be taken into account in interpreting these results.
Artificial Sweeteners — Enhancing Glycosylation to Treat Muscular Dystrophies
Authors: Thomas A Rando
Journal: New England Journal of Medicine (2004)

Several congenital forms of muscular dystrophy are caused by mutations of glycosyltransferase genes. A recent study shows that overexpression of a specific glycosyltransferase compensates for the deficits produced by other mutant glycosyltransferases, raising the hope that a single therapy could be used to treat different forms of the disorder.
Meta-Iodobenzylguanidine Iodine-123 and Cardiac Adrenergic Activity in Familial Dilated Cardiomyopathy
Authors: Elisabete Martins, Ana Oliveira, José Silva-Cardoso, Teresa Faria, Teresa Pinho, Manuel Campelo, António Madureira, Orquídea Ribeiro, Isabel Ramos, Jorge G. Pereira, Francisco Rocha-Gonçalves
Journal: JACC. Cardiovascular imaging (2010)
P62 Thoroplastic Reconstruction Following Chest Wall Resection
Authors: A Lai, M Jones, C Duff
Journal: Thorax (2013)

<h3>Background</h3> Reconstructive procedures following chest wall resection continue to improve. This study reviews our experience of chest wall reconstruction with multidisciplinary approach. <h3>Methods</h3> We conducted a retrospective review of 25 patients who underwent chest wall reconstruction in our department between September 2006 and April 2013. <h3>Results</h3> 13 cases were primary chest wall tumours. Underlying diseases included chondrosarcoma, osteosarcoma, sarcomas, primary and metastatic lung tumours, radionecrosis and Aspergilloma. Mean number of ribs resected was 3.5. Reconstruction was performed using Marlex mesh with methyl methacrylate in all patients. The exact nature of the resectional defect cannot be fully planned for reconstruction until after its creation. Muscle, myocutaneous and chimeric flaps were used. Soft tissue reconstruction was carried out using Latissimus Dorsi muscle or myocutaneous flaps in 10 patients, Pectoralis Major in 2 patients, Rectus Abdominis in 1 patient, Trapezius in 1 patients and Serratus Anterior in 1 patient. 3 patients had post-operative complications requiring re-admission. There were no cases of 30-day mortality on follow-up. <h3>Conclusions</h3> Chest wall resection and reconstruction with Marlex mesh had excellent results, and is useful for managing defects following chest wall resectionwith low morbidity. The importance of close collaboration between reconstructive and cardiothoracic surgery team is demonstrated.
Microalbuminuria Immunoassay Based on Antibodies Covalently Conjugated to Eupergit C-Coated Beads
Authors: Beka Solomon, Gideon Fleminger, Fidi Schwartz, Ram Doolman, Ben-Ami Sela
Journal: Diabetes Care (1992)

OBJECTIVE To develop a reliable, simple, and sensitive assay for microalbuminuria, based on covalent attachment of anti-HSA to oxirane-bearing polymethylmethacrylate beads (Eupergit CB6200). RESEARCH DESIGN AND METHODS Anti-HSA antibodies were coupled to CB6200 beads by reaction of their amino groups with the oxirane groups of the matrix. The capability of the beads to bind HSA from standard solutions or urine was evaluated and compared with the state of the art ELISA test. RESULTS The new bead immunoassay is sensitive and linear in the range of 1–25 mg/L, which is considered the low microalbuminuria range. When HSA levels in urine were tested, the intra- and interassay CV values ranged between 2.7 and 3.9% and between 5.6 and 6.6%, respectively. The long-term storage stability of the antibodies covalently bound on the beads was higher than of the same antibodies adsorbed on ELISA plates. After 16 wk of storage, the CV was about 7.3% with the bead assay, compared with 14% obtained for the ELISA test under the same experimental conditions. CONCLUSIONS A new procedure for microalbuminuria assay was developed, with Eupergit CB6200 beads as a solid support for covalent binding of the first antibody. Accuracy, sensitivity, reproducibility, and precision of the bead immunoassay were similar to those of commonly used immunoassays, as exemplified by the analysis of HSA in 53 clinical urine samples. The bead assay retains a low degree of variability over long storage periods, and the beads may be reapplied after a simple acid-washing procedure.
Extraordinary Disorders of Human Behavior
Authors: Sara C. Charles
Journal: JAMA (1983)

The editors of this collection, Extraordinary Disorders of Human Behavior , set out to collate material on rare and unusual disorders that is scattered throughout the psychiatric literature and to contemporize and update [the material] in one clinically relevant volume. Rationalizing that although the average clinical may see only one or two of these disorders in a lifetime, they justifiably contend that partial or fragmentary expressions of these disorders may be frequently observed in dream material, fantasies, and behaviors and, as such, should be of interest and fascination to all clinicians.  The reader, then, is newly introduced to or refamiliarized with, as the case may be, the gamut of situationspecific and idiopathic syndromes such as folie a deux, Ganser's syndrome, Gilles de la Tourette's, and Capgras' syndromes; the culturebound phenomena such as amok, latak, and wihtigo; paraphilias such as necrophilia, vampirism, and zoophilia; and a number of other syndromes that are
1103-195 Genetic predictive factors for restenosis in diabetic patients after percutaneous transluminal coronary angioplasty
Authors: Pascalle S Monraats, Willem R.P Agema, Aeilko H Zwinderman, Robbert J de Winter, Rene A Tio, Pieter A.F.M Doevendans, Harry J.G.M Crijns, Moniek P.M de Maat, Douwe E Atsma, Arnoud van der Laarse, Ernst E van der Wall, J Wouter Jukema
Journal: Journal of the American College of Cardiology (2004)
Mechanisms Underlying Pulmonary and Cardiac Complications of Electrically Induced Convulsions
Authors: M. D. Altschule, K. J. Tillotson
Journal: New England Journal of Medicine (1948)

THE changes in pulmonary function observed during electrically induced convulsions account for the development of atelectasis and, more rarely, lung abscess in patients receiving electroshock therapy. A convulsion induced by electric shock is ushered in by maximal forced expiration, which is then maintained throughout the seizure.1 2 3 Roentgenograms made at the height of the tonic phase of such seizures uniformly show an extreme degree of elevation of the diaphragm, together with some narrowing of the intercostal spaces; marked compression of the lung results (Fig. 1). With the end of the convulsion the patient relaxes, and the lungs re-expand to approximately their . . .
Fewer Major Amputations Among Individuals With Diabetes in Finland in 1997–2007
Authors: Tuija S. Ikonen, Reijo Sund, Maarit Venermo, Klas Winell
Journal: Diabetes Care (2010)

Complications occur in diabetes despite rigorous efforts to control risk factors. Since 2000, the National Development Programme for the Prevention and Care of Diabetes has worked to halve the incidence of amputations in 10 years. Here we evaluate the impact of the efforts undertaken by analyzing the major amputations done in 1997-2007.All individuals with diabetes (n = 396,317) were identified from comprehensive national databases. Data on the first major amputations (n = 9,481) performed for diabetic and nondiabetic individuals were obtained from the National Hospital Discharge Register.The relative risk for the first major amputation was 7.4 (95% CI 7.2-7.7) among the diabetic versus the nondiabetic population. The standardized incidence of the first major amputation decreased among the diabetic and nondiabetic populations (48.8 and 25.2% relative risk reduction, respectively) over 11 years, and the time from the registration of diabetes to the first major amputation was significantly longer, on average 1.2 years more. The cumulative five-year postamputation mortality among diabetic individuals was 78.7%.In our nationwide diabetes database, the duration from the registration of diabetes to the first major amputation increased, and the incidence of major amputations decreased almost 50% in 11 years. Approximately half of this change was due to the increasing size of the diabetic population. The risk for major amputation is more than sevenfold that among the nondiabetic population. These results pose a continuous challenge to improve diabetes care.
Ensuring a bright future for clinical research in surgery with trainee led research networks
Authors: A. G. Kolias, C. J. Cowie, A. Tarnaris, P. J. Hutchinson, P. M. Brennan
Journal: BMJ (2013)

The publication of the ROSSINI trial is a landmark in the short history of trainee led research networks in the UK. The trainee led West Midlands Research Collaborative (WMRC), with the support of experienced senior clinicians and researchers, designed and managed all aspects of ROSSINI, while trainees were responsible for driving recruitment in the 21 participating sites. The result was a well conducted trial, …
AUTOGENOUS, HOMOGENOUS OR HETEROGENOUS GRAFTS
Authors: Clarence A. McWilliams
Journal: JAMA (1924)

To the Editor:  —I am interested in settling the question of the value of any other kind of graft of organs or skin than autogenous grafts. Homogenous or heterogenous grafts are seldom, if ever, successful. This makes grafting of heterogenous testes, in rejuvenation operations, useless.  Will any surgeon who has performed homogenous or heterogenous graftings of skin or other organs kindly report positive or negative results as to whether or not the grafts were successful. Is it ever worth while grafting the skin from another individual?  Replies will be tabulated and published.
Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton
Authors: Tetsuro Takeda, Tammie McQuistan, Robert A. Orlando, Marilyn G. Farquhar
Journal: Journal of Clinical Investigation (2001)

Podocalyxin (PC), the major sialoprotein of glomerular epithelial cells (GECs), helps maintain the characteristic architecture of the foot processes and the patency of the filtration slits. PC associates with actin via ezrin, a member of the ERM family of cytoskeletal linker proteins. Here we show that PC is linked to ezrin and the actin cytoskeleton via Na+/H+-exchanger regulatory factor 2 (NHERF2), a scaffold protein containing two PDZ (PSD-95/Dlg/ZO-1) domains and an ERM-binding region. The cytoplasmic tail of PC contains a C-terminal PDZ-binding motif (DTHL) that binds to the second PDZ domain of NHERF2 in yeast two-hybrid and in vitro pull-down assays. By immunocytochemistry NHERF2 colocalizes with PC and ezrin along the apical domain of the GEC plasma membrane. NHERF2 and ezrin form a multimeric complex with PC, as they coimmunoprecipitate with PC. The PC/NHERF2/ezrin complex interacts with the actin cytoskeleton, and this interaction is disrupted in GECs from puromycin aminonucleoside–, protamine sulfate–, or sialidase-treated rats, which show a dramatic loss of foot processes, comparable to that seen in the nephrotic syndrome. Thus NHERF2 appears to function as a scaffold protein linking PC to ezrin and the actin cytoskeleton. PC/NHERF2/ezrin/actin interactions are disrupted in pathologic conditions associated with changes in GEC foot processes, indicating their importance for maintaining the unique organization of this epithelium.
Remote preconditioning protects the heart by activating myocardial PKCε-isoform
Authors: S Wolfrum
Journal: Cardiovascular Research (2002)

Myocardial protection can be achieved by brief ischemia-reperfusion of remote organs, a phenomenon described as remote preconditioning (RPC). Since the intracellular mechanisms of RPC are not known, we tested the hypothesis that RPC might activate myocardial PKCepsilon, an essential mediator of classical ischemic preconditioning. Furthermore, we tried to delineate the mechanisms by which RPC is transduced to the heart with respect to the possible contribution of kinins and neuronal reflexes.Anesthetized rats were randomised to undergo either 30 min of waiting (controls) or RPC (brief mesenteric artery occlusion followed by reperfusion) in the absence or presence of chelerythrine (5 mg kg(-1)), a specific PKC inhibitor. Myocardial infarct size was measured by TTC staining after 30 min of coronary artery occlusion followed by 150 min of reperfusion. In separate sets of experiments RPC was performed with or without pretreatment with HOE140, a selective B(2)-antagonist or hexamethonium was used to explore the influence of ganglion blockade on RPC. Translocation of PKCepsilon from cytosol to the particulate fraction was measured by quantitative immunoblotting.RPC significantly reduced infarct size which was completely blocked by the PKC inhibitor. RPC shifted the ratio between cytosolic and particulate PKCepsilon, an indicator for PKC-activation, from 0.95+/-0.06 in controls to 0.41+/-0.09 (P<0.05), and this effect was abolished by HOE140. Activation of PKCepsilon could not be achieved after pretreatment with HEX (0.69+/-0.06 in HEX vs. 0.78+/-0.06 in HEX+RPC).RPC activates myocardial PKCepsilon through a neuronal and bradykinin-dependent pathway. We assume that activation of PKCepsilon is an important step in cardioprotection induced by remote preconditioning.
Peptic Ulcer in Adults
Authors: G.N. Christodoulou, B.H. Alevizos, E. Konstantakakis
Journal: Psychotherapy and Psychosomatics (1983)

34 male peptic ulcer patients were compared to (a) a group of 37 healthy controls and (b) a group of 36 hospitalized controls suffering from illnesses unrelated to the gastrointestinal tract. Patients and controls were submitted to the Eysenck personality inventory, Foulds' hostility questionnaire, Langner's 22-item questionnaire, the Hopkins symptom checklist, Zung's self-rating anxiety scale, Spielberger's state-trait anxiety inventory, Zung's and Beck's rating scales for depression, and the 43-item life event inventory by Holmes and Rahe. All patients suffered from duodenal ulcer. The parameters that differentiated to a statistically significant degree the peptic ulcer patients from either one or both groups of controls were: (a) neuroticism, (b) trait and state anxiety, (c) guilt, (d) general psychopathology, and (e) stressful life events. Additionally, more than 50% of patients had at least one first-degree relative with peptic ulcer. These observations indicate that psychopathological, psychosocial, characterological and hereditary factors are important pathogenetic contributors in peptic ulcer.