tbuckley/cabot-search huggingface dataset:
Changing pattern of respiratory tuberculosis in the UK in adult patients from the Indian subcontinent
Authors: L. P. Ormerod, O. R. McCarthy, E. A. Paul
Journal: Thorax (1997)

BACKGROUND: Clinical observations over a 12 year period have suggested a changing pattern of adult respiratory tuberculosis in patients from the Indian subcontinent in two districts of the United Kingdom with a high incidence of tuberculosis. METHODS: Details of all patients for the period 1981-92 residing in the Newham and Blackburn districts aged 15 and over whose ethnic origin was from the Indian subcontinent (n = 1308) were analysed by stepwise logistic regression to determine the relationship between sputum smear positivity, sputum culture positivity, and isolated mediastinal lymphadenopathy, year of notification, age, sex, ethnic group (Indian or Pakistani), and whether the patient had visited the Indian subcontinent within the last three years. RESULTS: The proportion of cases who were smear positive rose over the 12 years of the study, as did the proportion of culture positive cases. The proportion with isolated mediastinal lymphadenopathy fell. These changes took place in both districts. They were not explained by demographic changes in age, sex, or ethnic group, nor was there evidence that smear and culture positivity increased in those who had recently visited India or Pakistan. CONCLUSIONS: The pattern of tuberculosis in adult patients originating from the Indian subcontinent has altered over time towards that seen in the white population in the UK.
<i>EGFR</i> Variant Heterogeneity in Glioblastoma Resolved through Single-Nucleus Sequencing
Authors: Joshua M. Francis, Cheng-Zhong Zhang, Cecile L. Maire, Joonil Jung, Veronica E. Manzo, Viktor A. Adalsteinsson, Heather Homer, Sam Haidar, Brendan Blumenstiel, Chandra Sekhar Pedamallu, Azra H. Ligon, J. Christopher Love, Matthew Meyerson, Keith L. Ligon
Journal: Cancer Discovery (2014)

Abstract Glioblastomas (GBM) with EGFR amplification represent approximately 50% of newly diagnosed cases, and recent studies have revealed frequent coexistence of multiple EGFR aberrations within the same tumor, which has implications for mutation cooperation and treatment resistance. However, bulk tumor sequencing studies cannot resolve the patterns of how the multiple EGFR aberrations coexist with other mutations within single tumor cells. Here, we applied a population-based single-cell whole-genome sequencing methodology to characterize genomic heterogeneity in EGFR-amplified glioblastomas. Our analysis effectively identified clonal events, including a novel translocation of a super enhancer to the TERT promoter, as well as subclonal LOH and multiple EGFR mutational variants within tumors. Correlating the EGFR mutations onto the cellular hierarchy revealed that EGFR truncation variants (EGFRvII and EGFR carboxyl-terminal deletions) identified in the bulk tumor segregate into nonoverlapping subclonal populations. In vitro and in vivo functional studies show that EGFRvII is oncogenic and sensitive to EGFR inhibitors currently in clinical trials. Thus, the association between diverse activating mutations in EGFR and other subclonal mutations within a single tumor supports an intrinsic mechanism for proliferative and clonal diversification with broad implications in resistance to treatment. Significance: We developed a novel single-cell sequencing methodology capable of identifying unique, nonoverlapping subclonal alterations from archived frozen clinical specimens. Using GBM as an example, we validated our method to successfully define tumor cell subpopulations containing distinct genetic and treatment resistance profiles and potentially mutually cooperative combinations of alterations in EGFR and other genes. Cancer Discov; 4(8); 956–71. ©2014 AACR. See related commentary by Gini and Mischel, p. 876 This article is highlighted in the In This Issue feature, p. 855
Ex vivo differentiated endothelial and smooth muscle cells from human cord blood progenitors home to the angiogenic tumor vasculature
Authors: S Le Ricousse-Roussanne
Journal: Cardiovascular Research (2004)

Objectives: Recent studies have provided increasing evidence that postnatal neovascularization does not rely exclusively on sprouting of preexisting vessels, but also involves bone marrow-derived circulating endothelial precursors (BM-EPCs). Animal studies revealed that neovascularization of ischemic tissue can be enhanced by BM-EPCs transplantation. But a possible limitation to the use of vascular precursors for therapeutic angiogenesis is the relatively low number of these cells. In this study, we demonstrate that ex vivo expanded differentiated endothelial cells (ECs) and smooth muscle cells (SMCs), may home to the tumor vasculature allowing targeting of transgene expression to the neoangiogenic site. Methods: Mononuclear cells (MNCs) or CD34+-enriched cells were purified from cord blood. We have defined culture conditions in which we observed two types of clones easily differentiated according to their morphology: cobblestone or spindle-shaped. Phenotypic characterization was assessed by immunocytochemistry, flow cytometry analysis and polymerase reaction with reverse transcription. Formation of capillary-like network in vitro was studied in three-dimensional collagen culture. And recruitment of these cells to a tumoral neoangiogenic site was assessed into tumor-bearing Severe Combined Immunodeficient (SCID) mouse model. Results: The cobblestone cells uniformly positive for CD31, VE-cadherin, vWF, VEGF R1 and R2, ecNOS and incorporating acetylated LDL were ECs. Spindle-shaped cells expressed α-smooth muscle actin (α-SMA), Smooth Muscle Heavy Chain (SMHC), SM22 and calponin. They also displayed a carbachol-induced contractility in a medium containing IGF1. So we concluded that spindle-shaped cells were SMCs. ECs and SMCs interacted with each other to form a capillary like network in three-dimensional type I collagen culture. Moreover, these ex vivo differentiated cells are able to home to the tumor vasculature. Conclusion: We provide evidence that progenitors for ECs and SMCs circulate in human cord blood and differentiate into functional ECs and SMCs. These differentiated cells could provide a biomaterial for vascular cell therapy, because of their homing capacity to the neovascularization site.
<i>In vivo</i> RNA Interference–Mediated Ablation of <i>MDR1</i> P-Glycoprotein
Authors: Andrea Pichler, Noam Zelcer, Julie L. Prior, Annemieke J. Kuil, David Piwnica-Worms
Journal: Clinical Cancer Research (2005)

Abstract Multidrug resistance (MDR) remains a major obstacle to successful chemotherapeutic treatment of cancer and can be caused by overexpression of P-glycoprotein, the MDR1 gene product. To further validate a knockdown approach for circumventing MDR, we developed a P-glycoprotein inhibition strategy using short hairpin RNA interference (shRNAi) and now show efficacy and target specificity in vivo. Two of eight tested shRNAi constructs targeted against human MDR1 mRNA inhibited expression of P-glycoprotein by &amp;gt;90%, whereas control shRNAi had no effect. Ablation of P-glycoprotein in cells stably transduced with retroviral-mediated shRNAi was documented by Western blot and functionally confirmed by increased sensitivity of MDR1-transfected cells toward the cytotoxic drugs vincristine, paclitaxel, and doxorubicin as well as by transport of 99mTc-Sestamibi. shRNAi-mediated down-regulation of P-glycoprotein transport activity both in cultured cells and in tumor implants in living animals could be followed by direct noninvasive bioluminescence imaging using the Renilla luciferase fluorophore, coelenterazine, a known P-glycoprotein transport substrate. Furthermore, after somatic gene transfer by hydrodynamic infusion of a MDR1-Firefly luciferase (MDR1-FLuc) fusion construct into mouse liver, the effect of shRNAi delivered in vivo on P-glycoprotein-FLuc protein levels was documented with bioluminescence imaging using d-luciferin. ShRNAi against MDR1 reduced bioluminescence output of the P-glycoprotein-FLuc reporter 4-fold in vivo compared with mice treated with control or scrambled shRNAi. Targeted down-regulation of a somatically transferred P-glycoprotein-eGFP fusion reporter also was observed using fluorescence microscopy. Our results show that shRNAi effectively inhibited MDR1 expression and function in cultured cells, tumor implants and mammalian liver, documenting the feasibility of a knockdown approach to reversing MDR in vivo.
Lactulose and Severe Lactic Acidosis
Authors: N. S. MANN
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 October 1985Lactulose and Severe Lactic AcidosisN. S. MANN, MD., F.R.C.P.(C), H. B. RUSSMAN, M.D., S. K. MANN, M.D., M. F. TSAI, M.D., M.P.H.N. S. MANN, MD., F.R.C.P.(C)Search for more papers by this author, H. B. RUSSMAN, M.D.Search for more papers by this author, S. K. MANN, M.D.Search for more papers by this author, M. F. TSAI, M.D., M.P.H.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-103-4-637_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In an excellent recent review on lactic acidosis (1), sorbitol has been listed as one cause. Advanced liver disease and end-stage renal disease are also known causes (2). Sorbitol, like lactulose, has been used in the management of hepatic encephalopathy (3) and lowers the stool pH. Lactulose given orally markedly lowers the colonic pH (4) because it reaches the colon unchanged and is acted on by colonic bacteria, which break it down into lactic, acetic, and formic acids. Acidic colonic contents trap ammonia, which is disposed of in the stools, facilitated by the additional laxative effect of...References1. KREISBERG R. Pathogenesis and management of lactic acidosis. Annu Rev Med. 1984;35:181-93. CrossrefMedlineGoogle Scholar2. KREISBERG R. Lactate homeostasis and lactic acidosis. Ann Intern Med. 1980;92:227-37. LinkGoogle Scholar3. RODGERKILEYBALINT JJJ. Comparison of results of long term treatment of chronic hepatic encephalopathy with lactulose and sorbitol. Am J Gastroenterol 1973;60:459-65. MedlineGoogle Scholar4. MANNBORKARNARENDERANKADIANMANNMARTIN NBKRSR. Effect of lactulose, neomycin and antacid on colonic pH recorded continuously with an implanted electrode. Am J Gastroenterol. 1979;72:141-5. MedlineGoogle Scholar5. PARKARIEFF RA. Treatment of lactic acidosis with dichloroacetate in dogs. J Clin Invest. 1982;70:853-62. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Veterans Administration Medical Center Texas A&M University Temple, TX 76501 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byD-lactic acidosis - a rare complication of short bowel syndromeHigh anion gap metabolic acidosis caused by D-lactateClinical use of plasma lactate concentration. Part 1: Physiology, pathophysiology, and measurementConstipation incidence and impact in medical critical care patientsLactic Acidosis: Recognition, Kinetics, and Associated PrognosisLactic Acidosis: From Sour Milk to Septic ShockLactic AcidosisLabetalolLactate MetabolismAcid-base disturbances in gastrointestinal disease 1 October 1985Volume 103, Issue 4Page: 637-637KeywordsAcidsAmmoniaBacteriaBrain diseasesColonLactic acidosisLiver diseasesRenal failure ePublished: 1 December 2008 Issue Published: 1 October 1985 PDF downloadLoading ...
Rejection of first-set skin allografts in man. the microvasculature is the critical target of the immune response.
Authors: H F Dvorak, M C Mihm, A M Dvorak, B A Barnes, E J Manseau, S J Galli
Journal: The Journal of Experimental Medicine (1979)

Recent reports of microvascular injury in delayed hypersensitivity skin reactions prompted us to reexamine the pathogenesis of first-set skin allograft rejection in man using morphologic techniques that allowed both extensive vessel sampling and unequivocal evaluation of microvascular endothelium. We here report that widespread microvascular damage is a characteristic, early consequence of the cellular immune response to first-set human skin allografts and is qualitatively similar to, but substantially more extensive than, that occurring in delayed hypersensitivity reactions. Microvascular damage in invariably preceded significant epithelial necrosis and affected initially and primarily those venules, arterioles, and small veins enveloped by lymphocytes. Vessels of both the allograft itself and the underlying graft bed (recipient tissue) were equally affected. These data suggest that endothelial cells of the microvasculature are the critical target of the immune response in first-set vascularized skin allograft rejection in man and that rejection can be attributed largely to ischemic infarction resulting from extensive microvascular damage. Other mechanisms, such as direct cellular contacts between infiltrating lymphocytes and epithelium, apparently played only a minor role. The findings presented here indicate that the rejection of first-set vascularized skin allografts, though induced by immunologically specific mechanisms, is primarily effected by final pathways that are relatively nonspecific and that may cause damage to both foreign and host vessels and cells. Rather than contradicting studies demonstrating the exquisite specificity of allograft rejection in other systems, these findings provide a further example of the heterogeneity of the cellular immune response. Recognition of the critical role of immunologically mediated microvascular injury may prove important both for an understanding of the biology of allograft rejection and for strategies aimed at prolonging allograft survival.
Adiponectin: More Than Just Another Fat Cell Hormone?
Authors: Manju Chandran, Susan A. Phillips, Theodore Ciaraldi, Robert R. Henry
Journal: Diabetes Care (2003)

Recent research has shown that adipose tissue is not simply an inert storage depot for lipids but is also an important endocrine organ that plays a key role in the integration of endocrine, metabolic, and inflammatory signals for the control of energy homeostasis. The adipocyte has been shown to secrete a variety of bioactive proteins into the circulation. These secretory proteins, which have been collectively named adipocytokines (1), include leptin (2), tumor necrosis factor (TNF)-α (3), plasminogen-activator inhibitor type 1 (PAI-1) (4), adipsin (5), resistin (6), and adiponectin (7). Adiponectin, the gene product of the adipose most abundant gene transcript 1 (apM1) (7), is a novel and important member of the adipocytokine family. Adiponectin cDNA was first isolated by large-scale random sequencing of the human adipose tissue cDNA library (7). It is a collagen-like protein that is exclusively synthesized in white adipose tissue, is induced during adipocyte differentiation, and circulates at relatively high (microgram/milliliter) concentrations in the serum. Both murine and human forms of adiponectin have been isolated independently by several groups, and various descriptive names have been given to the same compound by different investigators: adipocyte complement-related protein of 30 kilodalton (Acrp30) (8), Adipo Q (9), and gelatin binding protein of 28 kilodalton (GBP28) (10). The former two are murine analogs and the latter the human counterpart. Throughout this review, we will be referring to the protein by its most commonly used name, adiponectin.

Adiponectin has been postulated to play an important role in the modulation of glucose and lipid metabolism in insulin-sensitive tissues in both humans and animals. Decreased circulating adiponectin levels have been demonstrated in genetic and diet-induced murine models of obesity (11), as well as in diet-induced forms of human obesity (12). Low adiponectin levels have also been strongly implicated in the development of insulin resistance …
14-Day Variant of the Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone Regimen in Advanced-Stage Hodgkin’s Lymphoma: Results of a Pilot Study of the German Hodgkin’s Lymphoma Study Group
Authors: M. Sieber, H. Bredenfeld, A. Josting, T. Reineke, U. Rueffer, T. Koch, R. Naumann, F. Boissevain, P. Koch, P. Worst, M. Soekler, H. Eich, H.K. Müller-Hermelink, J. Franklin, U. Paulus, J. Wolf, A. Engert, V. Diehl
Journal: Journal of Clinical Oncology (2003)

Purpose: This multicenter pilot study assessed the feasibility and efficacy of a time-intensified bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) regimen given in 14-day intervals (BEACOPP-14) with granulocyte colony-stimulating factor (G-CSF) support in advanced Hodgkin’s lymphoma. Patients and Methods: From July 1997 until March 2000, 94 patients with Hodgkin’s lymphoma stage IIB, III, and IV were scheduled to receive eight cycles of BEACOPP-14. Consolidation radiotherapy was administered to regions with initial bulky disease or residual tumor after chemotherapy. Results: All patients were assessable for toxicity and treatment outcome. Eighty-six patients received the planned eight cycles of BEACOPP-14. Consolidation radiotherapy was given in 66 patients. Chemotherapy could generally be administered on schedule. Dose reductions varied among drugs but were generally low. Acute toxicity was moderate, with World Health Organization grade 3/4 leukopenia in 75%, thrombocytopenia in 23%, anemia in 65%, and infection in 12% of patients. A total of 88 patients (94%) achieved a complete remission. Four patients had progressive disease. At a median observation time of 34 months, five patients have relapsed, one patient developed a secondary non-Hodgkin’s lymphoma, and three deaths were documented. The overall survival and freedom from treatment failure rates at 34 months were 97% (95% confidence interval [CI], 93% to 100%) and 90% (95% CI, 84% to 97%), respectively. Conclusion: Acceleration of the BEACOPP baseline regimen by shortening cycle duration with G-CSF support is feasible and effective with moderate acute toxicity. On the basis of these results, the German Hodgkin’s Lymphoma Study Group will compare the BEACOPP-14 regimen with BEACOPP-21 escalated in a prospective multicenter randomized trial.
Chromoendoscopic surveillance in hereditary diffuse gastric cancer: an alternative to prophylactic gastrectomy?
Authors: D Shaw
Journal: Gut (2005)

<b>Background:</b> Hereditary diffuse gastric cancer (HDGC) is defined by germline mutations in the E-cadherin gene, <i>CDH-1</i>. The first family in which <i>CDH-1</i> mutations were identified was a large Maori kindred, where lifetime penetrance is 70%. Prophylactic gastrectomy is an unacceptable option for many mutation carriers. The results of annual chromoendoscopic surveillance using the methylene blue/congo red technique in 33 mutation carriers over a five year period are described. <b>Patients and methods:</b> Thirty three confirmed <i>CDH-1</i> mutation carriers (18 males, 15 females), median age 32 years (range 14–69), were enrolled in 1999–2003. Medical records, endoscopy, and pathology were reviewed retrospectively. <b>Results:</b> Over five years, 99 surveillance endoscopies were performed, of which 93 were chromo-dye enhanced. Sixty nine chromoendoscopies were normal. In 24 procedures, 1–6 pale areas/stomach (size 2–10 mm) were detected post chromo-dye application (totalling 56 pale lesions). One biopsy was taken from each pale lesion: 23 lesions (41%) showed signet ring cell carcinoma (10 patients), 10 lesions (18%) gastritis (four patients), and 23 (41%) normal mucosa (10 patients). No chromo-dyes were used in six procedures with macroscopic lesions (two HDGC, four ulceration). Total gastrectomies from patients with carcinoma were macroscopically normal but pathological mapping showed multiple microscopic foci of early signet ring cell carcinoma. Correlation of chromoendoscopic and gastrectomy findings showed that congo red/methylene blue detected carcinoma foci 4–10 mm in size but not foci &lt;4 mm. <b>Conclusions:</b> The use of chromoendoscopy following normal white light gastroscopy facilitated detection of early gastric carcinoma foci not visible with white light gastroscopy. If these findings are validated in other HDGC kindred, chromogastroscopy represents an improved surveillance technique that can be safely considered alongside prophylactic gastrectomy.
Guidelines for the diagnoses and treatment of adult lower respiratory tract infections: a true "European cooperative effort"
Authors: M. I. Restrepo, A. Anzueto
Journal: European Respiratory Journal (2005)

hroughout history, the diagnosis and treatment of lower respiratory tract infections (LRTIs) has been a ''European cooperative effort''.Since the experiments of R. Koch, many scientists have identified the role of infectious agents, including bacteria, in these conditions and different alternative treatments required to combat them.In 1888, E. de Freudenreich isolated bacterial secretions and noted their inherent, antibacterial properties.Later, in 1896, E. Duchesne noted that certain penicillium moulds killed bacteria, findings that were later confirmed by A. Fleming.We all know the history that follows …, but today we have new challenges to overcome.In the current issue of the European Respiratory Journal, WOODHEAD et al. [1] present the guidelines of the European Respiratory Society (ERS) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID), based on a systematical appraisal of the existing literature for diagnosis and management of adult LRTIs.These guidelines provide recommendations for the diagnosis and treatment of the three most common LRTIs: community-acquired pneumonia (CAP), acute exacerbations of chronic obstructive pulmonary disease (COPD; AECB) and exacerbations of bronchiectasis.
A Case of Paralysis Occurring on the Same Side as a Lesion of the Brain, and Accompanied by Epilepsy
Authors: W. Williams
Journal: BMJ (1876)

half inches in height, but of somewhat spare muscular development.On inspection, the patient lying on the back, there is no visible pulsatioii; but palpation reveals a pulsating tumour about the size of a hen's egg, situated about an inch to the left of the umbilicus ; but, on account of the immobility and resistance of the abdominal muscles,