tbuckley/cabot-search huggingface dataset:
96. Enforced HoxB4 Expressed Hematopoietic Stem Cells Transdifferentiate into Oligodendrocytes in Adult Mouse Brain
Authors: Noriko Miyake, Koichi Miyake, Sanae Hisayasu, Stefan Karlsson, Takashi Shimada
Journal: Molecular Therapy (2006)

Hematopoietic stem cell (HSC) gene therapy is potentially curative for a number of inherited and acquired disorders. Recent studies have suggested that circulating bone marrow (BM) cells can home in the brain and transdifferentiate into neural cells. Therefore, BM transplantation may be effective in preventing the progression of neurological deterioration in lysosomal storage disorders such as metachromatic leukodystrophy (MLD). However, this therapeutic expression in repopulating HSC. To overcome this problem, we analyze the effect of overexpression of HoxB4, which can expand HSC, in mouse BM cells by transplantation of MLD mice. 5FU treated GFP mouse BM cells were transduced with retroviral vector expressing HoxB4 (B4) or control retroviral vector expressing GFP (MIG). After expansion of these transduced cells in vitro for five days transplantation was performed into irradiated MLD mice. High level of engraftment was observed in B4 transplanted MLD mice (B4MLD) compared to MIG transplanted MLD mice (MIGMLD)(92.4 vs. 36.5 %). ASA enzyme activity in serum was also increased in B4MLD compared to MIGMLD (19.8 vs. 10.3 nm/mg/hr). To evaluate the contribution of bone marrow cells as carriers for gene therapy of neurological disorders, we studied the fate of transplanted BM cells in the adult mouse brain. Efficient GFP positive neuronal cells were detected in B4MLD brain compared to MIGMLD brain. Immunohistochemical staining showed that most of the GFP positive cells ware IbaI positive microglia cells as we and others reported. In addition, O4 positive oligodendocyte like cells were identified only in the B4MLD brain but not in the MIGMLD brain (O4 positive/GFP positive: 6/326 vs. 0/312). This is the first demonstration indicating that systemically infused HSCc could differentiate to oligodendrocytes in adult mouse brain. It was recently suggested that HoxB4 could play a role in oligodendrocyte maturation. Our data strongly support that HSCs transduced with HoxB4 expression vector are useful for ex vivo gene therapy of CNS disorders as carriers of production of therapeutic protein and for regeneration of oligodendrocytes to treat demyelinating disorders such as MLD, Krabbe disease, and multiple sclerosis.
August is medical staffing month
Authors: Iain Varley
Journal: BMJ (2006)

tion to act independently.It means that competence is present, as it is a prerequisite for the adequate execution of the activity.The ideas I have elaborated need further investigation.But it is essential that innovation of postgraduate training should focus on expert appraisal of performance in practice and that trainees be qualified once they can be trusted to bear the responsibility for specific, entrustable, professional activities.
Resolution of Bone Scan Changes in Hypertrophic Pulmonary Osteoarthropathy in Untreated Carcinoma of the Lung
Authors: VIDYA V. SAGAR, ROBERT L. MECKELNBURG, JOSEPHINE M. PICCONE
Journal: Clinical Nuclear Medicine (1978)

The bone scan appearance of hypertrophic pulmonary osteoarthropathy (HPO) in patients with pulmonary neoplasms and a variety of other lesions has been described by several investigators. It is well known that after therapy, the bone scan changes resolve. This report deals with a patient who had no therapy for a pulmonary neoplasm. In a study done three months later, changes in his initial bone scan that had suggested pulmonary osteoarthropathy had resolved completely, even though the patient had no treatment for his carcinoma.
P162 Comparison of clinical characteristics and outcomes of patients with PET positive vs PET negative solitary pulmonary nodules managed by a Lung MDT
Authors: P. Malhotra, N. Lovell, P. K. Plant, M. E. J. Callister, S. Karthik, A. Scarsbrook
Journal: Thorax (2011)

<h3>Background</h3> PET-CT is an important test in the management of patients with solitary pulmonary nodules (SPNs). There is a paucity of data on clinical characteristics, follow-up and outcomes of patients with PET negative nodules as compared to PET positive ones. <h3>Objective</h3> To compare the clinical characteristics and outcomes of patients with PET positive vs PET negative SPNs managed by the Lung MDT at a large teaching hospital in North England. <h3>Methods</h3> 144 patients (age range 32–92 years, 76 females) with SPNs measuring 8–29 mm discussed at the Lung MDT who had PET-CT scans over a 3 year period between 1st January 2007 and 31st December 2009 were identified retrospectively through the Lung Cancer database. Demographic data, nodule characteristics, MDT decisions, median time to diagnosis, and outcomes were evaluated. We tested for differences in characteristics between patients with PET positive and negative nodules using t test and Mann–Whitney U test for continuous variables, and χ<sup>2</sup> tests or Fisher exact tests as indicated for categorical variables. <h3>Results</h3> In comparison to PET positive nodules, PET negative ones were smaller, less likely to be spiculated, more often associated with an MDT decision to follow-up with serial CT scans, less likely to undergo surgical resection or have radical radiotherapy, had a longer median time to diagnosis, and were less likely to be malignant. The overall prevalence of malignancy in patients with PET negative nodules, however (15/41 [36.6%]) was higher than that reported in previous studies. This may be due to the higher prevalence of adenocarcinoma in our series. <h3>Conclusions</h3> Significant differences in clinical characteristics and outcomes have been demonstrated between patients with PET positive and PET negative solitary pulmonary nodules. The overall prevalence of malignancy in patients with PET negative nodules (15/41 [36.6%]) was higher than that reported in previous studies.
Dermatophyte Test Medium Screening Limitations
Authors: Ira F. Salkin
Journal: JAMA (1973)

<h3>To the Editor.—</h3> Jacobs and Russell recently reported in a LETTER TO THE EDITOR (224:1649, 1973) that the systemic zoopathogens<i>Histoplasma capsulatum, Blastomyces dermatitidis</i>, and<i>Coccidioides immitis</i>, as well as dermatophytes, induce a color change when grown on dermatophyte test medium (DTM). They suggested that in regions where these zoopathogens are endemic, DTM could be employed as a screening test to "rule out" the fungi as causative agents in cases of undefined upper respiratory tract infections. Although I have noted similar results with respect to the development of systemic pathogens, I have also observed that common airborne saprophytes can cause a color change on DTM. In contrast to the instances of saprophytic contamination noted by Taplin et al,<sup>1</sup>I found that many of these molds are capable of inducing a change from straw yellow to deep red within seven to nine days. Moreover, they are morphologically indistinguishable in gross DTM
Abstract 5554: The proteome analysis of human lung adenocarcinoma
Authors: Keikou Tei, Anna Kakehashi, Shotaro Yamano, Min Wei, Noritoshi Nishiyama, Hideki Wanibuchi
Journal: Cancer Research (2010)

Abstract Lung cancer is the leading cause of cancer death in the worldwide. Despite advances in early diagnostic methods and treatment modarities, lung cancer is often diagnosed at an advanced stage and has a poor prognosis. There is a need for the development of new biomarkers for early detection, defining cancer risk, prognosis, and therapy targets. The purpose of this study was to investigate the molecular background of lung carcinogenesis and to search useful biomarkers for clinical treatment including early detection and prognosis prediction of lung cancer by performing proteome analysis of human lung adenocarcinoma. Subjects were cases with primary lung adenocarcinoma on which surgical resection was performed. Tumor and adjacent non-tumor tissue sample were collected and proteome analysis was carried out. All through the examined cases, 52 proteins were found overexpressed and 13 proteins localized in extracellular space were detected and these proteins were thought as potential biomarkers associated with lung adenocarcinoma. We noticed one protein of them and performed immunohistochemical staining, 94% of cases were expressed. We assessed the statistical significance of the associations between expression level of this protein and clinicopathologic variables, it was showed that this protein had possibility to be a novel prognosis prediction biomarker of lung adenocarcinoma. This study enables the indentification of biomarker candidates for novel tumor markers and therapetic targets that will eventually lead to early detection, prevention and treatment of cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5554.
A multiple ligand-binding radioimmunoassay of diiodotyrosine.
Authors: J C Nelson, R M Weiss, J E Lewis, R B Wilcox, F J Palmer
Journal: Journal of Clinical Investigation (1974)

A radioimmunoassay has been developed for the measurement of 3,5-diiodo-L-tyrosine (DIT) in serum. DIT was coupled to porcine thyroglobulin (PTg) with a molar ratio of 205:1. Rabbits were immunized with 1 mg of immunogen emulsified in complete Freund's adjuvant. Sera were screened for their ability to bind trace amounts of [125I]DIT. A serum that bound 40% of the tracer at a final dilution of 1:1,750 was used in the assay. Assay specificity was improved by the use of thyroxine (T4)-binding globulin as a second ligand-binding protein to decrease T4 and triiodothyronine (T3) cross-reactivity with the antibody. Double antibody and polyethylene glycol radioimmunoassays were compared. DIT present in the second antiserum shifted the double antibody assay standard curve and altered estimates of assay specificity and assay sensitivity. By using the polyethylene glycol system and butanol:ethanol extracts of serum, DIT was measured in human serum. In 35 apparently healthy young adult controls DIT levels averaged 156 ng/100 ml. Random DIT levels averaged 158 ng/100 ml in 11 untreated hyperthyroid patients and 84 ng/100 ml in 15 untreated primary hypothyroid patients. No diurnal pattern in DIT levels could be demonstrated. Thyroid-stimulating hormone administration led to a variable but small rise in DIT levels, but short term T3 suppression was not associated with a measurable fall in DIT concentrations. Paired serum samples from the carotid artery and thyroid vein of 10 euthyroid goiter patients and one patient with a toxic solitary adenoma all showed a positive transthyroidal gradient indicating the thyroidal release of DIT in each patient. Measurable DIT levels of 45, 47, 68, and 80 ng/100 ml, respectively, were found in four fasting athyrotic patients indicating that the thyroid is not the only source of serum DIT.
Immunological mechanisms in the pathogenesis of vinyl chloride disease.
Authors: A M Ward, S Udnoon, J Watkins, A E Walker, C S Darke
Journal: BMJ (1976)

Vinyl chloride (VC) disease is a multisystem disorder incorporating Raynaud9s phenomenon, acro-osteolysis, thrombocytopenia, portal fibrosis, and hepatic and pulmonary dysfunction. Immunological and immunochemical investigations showed the presence of circulating immune complexes in 19 out of 28 patients with the disease and in a further two out of 30 workers exposed to VC. The immunological data were reviewed in relation to the clinical picture of the disease and to the available evidence on the metabolism of VC. The results suggest that VC disease is an immune complex disorder and that the immune response is initiated by the adsorption of VC or a metabolite on to tissue or plasma protein.
Anovulatory and ovulatory infertility: results with simplified management.
Authors: M G Hull, P E Savage, D R Bromham
Journal: BMJ (1982)

A simplified scheme for the management of anovulatory and of ovulatory (usually called unexplained) infertility was evaluated in 244 women. Eighteen patients were excluded because of primary ovarian failure, 164 were treated for ovulatory failure, and 62 with ovulatory infertility remained untreated. Twenty-five patients had a properly validated negative postcoital test. In the remaining 201 patients the two-year conception rates were 96% in patients with amenorrhoea, 83% in those with oligomenorrhoea, 74% in those with luteal deficiency, and 88% in those with ovulatory infertility. Comparison with normal rates implied that amenorrhoea represents a pure form of ovulatory failure that is completely correctable whereas in other conditions unexplained factors also contribute to infertility though to a much smaller extent than was previously thought.
vCJD and the gut: implications for endoscopy
Authors: M W Head, J W Ironside
Journal: Gut (2006)

Surveillance for infection by endoscopy for variant CJD and other human prion diseases

The agents responsible for transmissible spongiform encephalopathies or prion diseases target the central nervous system, but their unique nature and pathophysiology has meant that prion diseases have made an impact in disciplines as diverse as dentistry and transfusion medicine, in large measure because of their resistance to decontamination by conventional means.1

In 1996, a new variant form of Creutzfeldt–Jakob disease (CJD) was described in the UK that preferentially affects young adults, resulting in a disease that often presents with psychiatric symptoms progressing to ataxia, dementia and terminating in akinetic mutism.2 The cause of this disease was proposed to be oral exposure to the bovine encephalopathy (BSE) agent, and subsequent studies have only served to strengthen this link, with no credible alternative explanation having been proposed.3–6 All human prion diseases are progressive and uniformly fatal neurodegenerative conditions, and, in the case of the acquired forms (iatrogenic CJD and kuru), associated with potentially very long incubation periods.7 Host genetics substantially influence these diseases: familial prion diseases are closely associated with mutations in the prion protein gene ( PRNP ), and the methionine /valine polymorphism at PRNP codon 129 appears to influence susceptibility, incubation period and in some respects disease phenotype.7

Our understanding of the pathogenesis of prion diseases has been greatly aided by the development of methods to detect and localise abnormal forms of the prion protein (PrPSc), which is the major, if not the sole, component of the infectious agent.7 Variations of standard immunohistochemical methods and Western blotting that use protease digestion and other discriminant steps to distinguish between the ubiquitous normal form of the prion protein (PrPC) and PrPSc have been used. With such tools, the distribution of this protease-resistant …
Conflict of Interest in Medical Research, Education, and Practice <i>Institute of Medicine, Committee on Conflict of Interest in Medical Research, Education, and Practice, edited by Bernard Lo and Marilyn J. Field</i> . Washington, DC:National Academies Press, 2009. 440 pp. ISBN: 978-0-309-13188-9, $54.95. 
Authors: David B. Resnik
Journal: Environmental Health Perspectives (2010)
Intranuclear Trafficking of Episomal DNA Is Transcription-dependent
Authors: Joshua Z Gasiorowski, David A Dean
Journal: Molecular Therapy (2007)

Our aim is to characterize the poorly understood mechanisms that influence episomal transgene expression within the nucleus. We found that plasmid DNA micro-injected directly into a nucleus moves into a speckled pattern and occupies less nuclear volume than bovine serum albumin (BSA) or other inert molecules after 4 hours. In addition, plasmids that contain eukaryotic regulatory sequences and actively transcribe transgenes condense into a few select areas of the nucleoplasm and occupy less nuclear volume than bacterial vectors. This suggests that episomal DNA moves in a sequence and transcription-dependent manner. We have also found that plasmids traffic to specific subnuclear domains depending on their sequence. Our experiments show that plasmids with polymerase II regulatory elements will target to nuclear spliceosome regions, while plasmids with the polymerase I promoter often traffic into nucleoli. Further elucidation of intranuclear plasmid trafficking behavior may lead to a better understanding of gene expression, and thereby help to improve basic laboratory techniques and clinical gene therapies.
Growth in renal failure.
Authors: C Chantler, R Counahan, V J Wass, M M El-Bishti
Journal: BMJ (1977)

reported a rise of 22 beats/min after a similar dose in acute asthma, while we have shown a rise of 28 beats/min one minute after salbuta- mol 200 xjg injected over a one-minute period to convalescent asthmatics.5 Indeed, Mr Neville and his colleagues reported a rise of 31 beats/min on completion of their intravenous injection.It would seem likely that had Professor Femi-Pearse measured the pulse rate sooner after completion of the bolus injection of salbutamol a greater tachycardia would have been apparent.In view of these other reports we feel that salbutamol should be administered intravenously slowly (over at least five minutes) and that, with time, cardiotoxic effects or deaths will be observed if this effective bronchodilator is given rapidly as suggested.
DIFFERENTIAL EFFECT OF FACTORS IN AN ACTIVITY THERAPY PROGRAM
Authors: DAVID LEVINE, HARRY K. MARKS, RICHARD HALL
Journal: American Journal of Psychiatry (1957)

Eighty patients on an acute intensive treatment ward of a Veterans Administration neuropsychiatric hospital were divided into 4 groups matched for age, diagnosis and number of months of previous psychiatric hospitalization. Each of 2 trained activity therapists took one of these groups daily for a half day in a traditional occupationaltherapy type of situation and one group daily for a half day on a lawn-mowing detail using hand mowers on the hospital lawn. After 12 weeks the degree of improvement shown by each patient was rated by the ward psychiatrist who did not know the assignments of the particular patient. The results indicate that the nature of the therapeutic activities differed, and that these important differences, plus the wide differences in the personalities of the therapists, greatly affect patient improvement and readiness for discharge. Patients mowing the lawn showed significantly more improvement than patients working in O.T. (P=.004). It would appear that for the type of psychotic patient included in this study, the simple, co-operative and useful activity of mowing the lawn is more beneficial than the less vigorous, more potentially creative, more complex, but possibly more isolated activity of individual occupational therapy projects.
Targeting Vacuolar H+-ATPases as a New Strategy against Cancer
Authors: Stefano Fais, Angelo De Milito, Haiyan You, Wenxin Qin
Journal: Cancer Research (2007)

Abstract Growing evidence suggests a key role of tumor acidic microenvironment in cancer development, progression, and metastasis. As a consequence, the need for compounds that specifically target the mechanism(s) responsible for the low pH of tumors is increasing. Among the key regulators of the tumor acidic microenvironment, vacuolar H+-ATPases (V-ATPases) play an important role. These proteins cover a number of functions in a variety of normal as well as tumor cells, in which they pump ions across the membranes. We discuss here some recent results showing that a molecular inhibition of V-ATPases by small interfering RNA in vivo as well as a pharmacologic inhibition through proton pump inhibitors led to tumor cytotoxicity and marked inhibition of human tumor growth in xenograft models. These results propose V-ATPases as a key target for new strategies in cancer treatment. [Cancer Res 2007;67(22):10627–30]
940. Chemotherapeutic Agent DFMO as an Intensifier of Suicide Gene Therapy
Authors: Tiina Wahlfors, Tanja Hakkarainen, Juhani Jänne, Leena Alhonen, Jarmo Wahlfors
Journal: Molecular Therapy (2006)

Even though suicide gene therapy with herpes simplex virus thymidine kinase have recently demonstrated to be an effective way to treat cancer patients, there is still need for improvement before a true clinical success. We have earlier demonstrated the enhancement of the HSV-TK/GCV gene therapy with ornithine decarboxylase (ODC) inhibitor DFMO in vitro. ODC is a rate-limiting enzyme in polyamine biosynthetic pathway and is frequently up-regulated in preneoplastic cells. By inhibiting the ODC activity, DFMO causes polyamine deprivation that inhibits cell growth and division. Here we show the utility of combination of polyamine biosynthesis inhibition and HSV-TK/GCV gene therapy in nude mouse model.
Botulism in an Adult Associated with Food-Borne Intestinal Infection with<i>Clostridium botulinum</i>
Authors: John K. Chia, Jonathan B. Clark, Caroline A. Ryan, Matthew Pollack
Journal: New England Journal of Medicine (1986)

Botulism is a neuroparalytic illness caused by the action of a heat-labile neurotoxin elaborated by Clostridium botulinum. Botulism in adults typically results from ingestion of preformed toxin in contaminated food, whereas in botulism in infants and in wound botulism, the neurotoxin is produced in vivo after multiplication of C. botulinum in the intestinal tract or infected wound, respectively.1 A fourth category, "classification undetermined," which was recently established by the Centers for Disease Control, includes cases occurring in persons older than one year of age in which it is not possible to implicate a specific food source on the basis . . .
Nitrite-generated NO circumvents dysregulated arginine/NOS signaling to protect against intimal hyperplasia in Sprague-Dawley rats
Authors: Matthew J. Alef, Raghuveer Vallabhaneni, Evie Carchman, Sidney M. Morris, Sruti Shiva, Yinna Wang, Eric E. Kelley, Margaret M. Tarpey, Mark T. Gladwin, Edith Tzeng, Brian S. Zuckerbraun
Journal: Journal of Clinical Investigation (2011)

Vascular disease, a significant cause of morbidity and mortality in the developed world, results from vascular injury. Following vascular injury, damaged or dysfunctional endothelial cells and activated SMCs engage in vasoproliferative remodeling and the formation of flow-limiting intimal hyperplasia (IH). We hypothesized that vascular injury results in decreased bioavailability of NO secondary to dysregulated arginine-dependent NO generation. Furthermore, we postulated that nitrite-dependent NO generation is augmented as an adaptive response to limit vascular injury/proliferation and can be harnessed for its protective effects. Here we report that sodium nitrite (intraperitoneal, inhaled, or oral) limited the development of IH in a rat model of vascular injury. Additionally, nitrite led to the generation of NO in vessels and SMCs, as well as limited SMC proliferation via p21Waf1/Cip1 signaling. These data demonstrate that IH is associated with increased arginase-1 levels, which leads to decreased NO production and bioavailability. Vascular injury also was associated with increased levels of xanthine oxidoreductase (XOR), a known nitrite reductase. Chronic inhibition of XOR and a diet deficient in nitrate/nitrite each exacerbated vascular injury. Moreover, established IH was reversed by dietary supplementation of nitrite. The vasoprotective effects of nitrite were counteracted by inhibition of XOR. These data illustrate the importance of nitrite-generated NO as an endogenous adaptive response and as a pathway that can be harnessed for therapeutic benefit.