tbuckley/cabot-search huggingface dataset:
Augmentation of Postnatal Neovascularization With Autologous Bone Marrow Transplantation
Authors: Satoshi Shintani, Toyoaki Murohara, Hisao Ikeda, Takafumi Ueno, Ken-ichiro Sasaki, Junli Duan, Tsutomu Imaizumi
Journal: Circulation (2001)

Background —Endothelial progenitor cells (EPCs) have been identified in adult human peripheral blood. Because circulating EPCs should originate from bone marrow (BM), we examined whether BM mononuclear cells (BM-MNCs) can give rise to functional EPCs and whether transplantation of autologous BM-MNCs might augment angiogenesis and collateral vessel formation in a rabbit model of hindlimb ischemia. Methods and Results —Rabbit BM-MNCs were isolated by centrifugation through a Histopaque density gradient and cultured on fibronectin. EPCs developed from BM-MNCs in vitro, as assessed by acetylated LDL incorporation, nitric oxide (NO) release, and expression of von Willebrand factor and lectin binding. Unilateral hindlimb ischemia was surgically induced in rabbits (n=8), and fluorescence-labeled autologous BM-MNCs were transplanted into the ischemic tissues. Two weeks after transplantation, fluorescence microscopy revealed that transplanted cells were incorporated into the capillary network among preserved skeletal myocytes. In contrast, transplanted autologous BM-fibroblasts did not participate in EC capillary network formation (n=5). Then, in an additional 27 rabbits, saline (control; n=8), autologous BM-MNCs (n=13; 6.9±2.2×10 6 cells/animal), or BM-fibroblasts (n=6; 6.5±1.5×10 6 cells/animal) were injected into the ischemic tissues at postoperative day 7. Four weeks after transplantation, the BM-MNC–transplanted group had more angiographically detectable collateral vessels (angiographic score: 1.5±0.34 versus 0.94±0.26 and 1.1±0.14; P &lt;0.05), a higher capillary density (23±5.8 versus 10±1.9 and 11±0.8 per field; P &lt;0.001), and a greater laser Doppler blood perfusion index (505±155 versus 361±35 and 358±22 U; P &lt;0.05) than the control and BM-fibroblast–transplanted groups. Conclusions —Direct local transplantation of autologous BM-MNCs seems to be a useful strategy for therapeutic neovascularization in ischemic tissues in adults, consistent with “therapeutic vasculogenesis.”
The Descriptive Epidemiology of Commonly Occurring Mental Disorders in the United States
Authors: Ronald C. Kessler, Philip S. Wang
Journal: Annual Review of Public Health (2008)

Data are reviewed on the descriptive epidemiology of commonly occurring DSM-IV mental disorders in the United States. These disorders are highly prevalent: Roughly half the population meets criteria for one or more such disorders in their lifetimes, and roughly one fourth of the population meets criteria in any given year. Most people with a history of mental disorder had first onsets in childhood or adolescence. Later onsets typically involve comorbid disorders. Some anxiety disorders (phobias, separation anxiety disorder) and impulse-control disorders have the earliest age of onset distributions. Other anxiety disorders (panic disorder, generalized anxiety disorder, post-traumatic stress disorder), mood disorders, and substance disorders typically have later ages of onset. Given that most seriously impairing and persistent adult mental disorders are associated with child-adolescent onsets and high comorbidity, increased efforts are needed to study the public health implications of early detection and treatment of initially mild and currently largely untreated child-adolescent disorders.
Most Early Disseminated Cancer Cells Detected in Bone Marrow of Breast Cancer Patients Have a Putative Breast Cancer Stem Cell Phenotype
Authors: Marija Balic, Henry Lin, Lillian Young, Debra Hawes, Armando Giuliano, George McNamara, Ram H. Datar, Richard J. Cote
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The presence of disseminated tumor cells (DTC) in the bone marrow of breast cancer patients is an acknowledged independent prognostic factor. The biological metastatic potential of these cells has not yet been shown. The presence of putative breast cancer stem cells is shown both in primary tumors and distant metastases. These cells with a CD44+CD24−/low phenotype represent a minor population in primary breast cancer and are associated with self-renewal and tumorigenic potential. Recognizing the potential effect of prevalence of putative stem cells among DTC, we evaluated the bone marrow DTC. Experimental Design: We employed the double/triple-staining immunohistochemistry protocol and modified the established bone marrow cytokeratin (CK) staining protocol by adding steps for additional antigens, CD44 and/or CD24. We evaluated 50 bone marrow specimens, previously categorized as CK+ from early breast cancer patients. CK+ cells were examined for CD44 and CD24 expression by light microscopy, fluorescence microscopy, and spectral imaging. Results: We detected the putative stem cell–like phenotype in all CK+ specimens. The mean prevalence of putative stem/progenitor cells was 72% and median prevalence was 65% (range, 33-100%) among the overall DTC per patient, compared with primary tumors where this phenotype is reported in &amp;lt;10% of cells. Conclusions: This is the first evidence of the existence of the putative stem-like phenotype within the DTC in bone marrow in early breast cancer patients. All patients had a putative stem cell phenotype among the DTC and most individual DTC showed such phenotype. Future molecular characterization of these cells is warranted.
Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression.
Authors: Chad A Dickey, Peter Ash, Natalia Klosak, Wing C Lee, Leonard Petrucelli, Michael Hutton, Christopher B Eckman
Journal: Molecular Neurodegeneration (2006)

The microtubule-associated protein tau (MAPT) is a pathological component of several neurodegenerative diseases and clinical dementias. Here, we have investigated the effects of a series of commercially available FDA-approved compounds and natural products on total tau protein levels using a cell-based approach that allows for the rapid and efficient measurement of changes in protein expression. The compounds that reduced tau largely fell within 3 functional categories with the largest percentage being microtubule regulators. Several of these candidates were validated in both a human neuroglioma and a human neuroblastoma cell line. While these drugs lead to a rapid reduction in tau protein levels, a selective decrease in MAPT mRNA expression was also observed. These findings suggest that the identified compounds that reduce tau levels may act either through direct effects on the MAPT promoter itself or by altering a feedback transcriptional mechanism regulating MAPT transcription. This is particularly interesting in light of recent evidence suggesting that MAPT 5' UTR mutations in late-onset PD and PSP cases alter the expression of tau mRNA. In fact, one of the compounds we identified, rotenone, has been used extensively to model PD in rodents. These observations may provide key insights into the mechanism of tau turnover within the neuron while also providing the first evidence that selectively reducing tau protein levels may be possible using compounds that are FDA-approved for other uses.
Increased Plasma Amylin in Type 1 Diabetic Patients After Kidney and Pancreas Transplantation: A sign of impaired -cell function?
Authors: M. Stadler
Journal: Diabetes Care (2006)

OBJECTIVE—In response to hyperglycemia, β-cells release insulin and C-peptide, as well as islet amyloid pancreatic polypeptide, which is involved in glucose homeostasis. After successful pancreas-kidney transplantation (PKT), type 1 diabetic patients may revert to a nondiabetic metabolism without exogenous insulin therapy and re-secrete all β-cell hormones.
Is the simple versus complex classification of concussion a valid and useful differentiation?
Authors: M Makdissi
Journal: British Journal of Sports Medicine (2009)

Background: At the Second International Conference on Concussion in Sport, concussion was classified as “simple” or “complex” based largely on duration of clinical features. The purpose of the classification system was to assist clinicians in identifying higher grades of injury severity and guide injury management. The aim of the current paper is to review the validity and clinical usefulness of the simple versus complex classification system. Study design: Qualitative review of the literature on concussion in sport, with a focus on time course of clinical recovery and prognostic factors. Intervention: Pubmed, Medline and Sport Discus databases were reviewed. Fifty journal articles were included in the review. Results: Prospective studies support the recovery of symptoms, balance deficits and cognitive impairment in the majority of concussed athletes within 10 days of injury. However, clinical factors that predict higher grades of injury severity or poor outcome following concussion remain unclear. At present, concussion severity can only be accurately determined in retrospect after all clinical features have resolved. Conclusion: It is recommended that concussion in sport be considered as a single entity. Clinical factors that have demonstrated to be associated with longer duration of symptoms (for example, post-traumatic amnesia) or poor outcome (for example, repetitive head injury) may serve as “modifying” factors to assist the treating practitioner in identifying potential for higher grades of injury severity or adverse outcomes.
Infiltrating ductal carcinoma: infiltrates at the exit site of a central venous access port device
Authors: I. Moya Horno, L.A. Fernández Morales, E. Dalmau Portulas, M.A. Seguí Palmer, J. Font Renom, O. Aparicio Rodríguez, J. Falcó Fages, R. Querol Niñerola, M. Pampols Felip, E. Saigí Grau
Journal: Annals of Oncology (2010)
Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma
Authors: G. Riethmüller, R. Gruber, E. Schneider-Gädicke, G. Schlimok, J. Witte, R. Raab, R. Pichlmayr, H. Pichlmaier, W. Schmiegel, P. Buggisch, K. Höffken, H. Hirche, Rudolf Pichimayr, Peter Buggisch, Jens Witte, None German Cancer Aid –A Study Group
Journal: The Lancet (1994)
Regional Coronary Venous Oxygen Saturation and Myocardial Oxygen Tension following Abrupt Changes in Ventricular Pressure in the Isolated Dog Heart
Authors: WALTER J. GAMBLE, C. GRANT LAFARGE, DONALD C. FYLER, JONATHAN WEISUL, R. GRIER MONROE
Journal: Circulation Research (1974)

Regional coronary venous oxygen saturation and myocardial oxygen tension (PO 2 ) in isolated dog hearts were measured using two different methods--a new technique of microscopic oximetry and an improved oxygen electrode. Both methods yielded similar results. In studies of the isolated perfused dog heart developing a constant left ventricular systolic pressure, mean coronary venous oxygen saturation of blood in the subendocardial veins of the left ventricle was significantly lower than that in the subepicardial veins. Following abrupt increases in systolic pressure, subendocardial coronary venous saturations fell to even lower levels. Following abrupt decreases in systolic pressure, the mean subendocardial coronary venous oxygen saturation increased to levels above those in the blood of the subepicardial veins. These findings agree with the hypothesis that transient underperfusion and overperfusion of the subendocardial layers of the left ventricle occur with abrupt increases and decreases in ventricular pressure, respectively.
Evidence for a national problem: continued rise in tuberculosis case numbers in urban areas outside London: Figure 1
Authors: Michelle E Kruijshaar, Ibrahim Abubakar, Martin Dedicoat, Graham H Bothamley, Helen Maguire, Jonathan Moore, Jonathan Crofts, Marc Lipman
Journal: Thorax (2012)

WHO standards for tuberculosis (TB) control require monitoring and evaluation of TB control programmes. In London, TB rates have stabilised at 44 per 100 000 since 2005. In 38 urban areas outside London with TB rates above the national average, these continued to rise after 2004, to 28 per 100 000 in 2008 (15% increase). London has the highest proportion of TB cases in certain risk groups, but these are increasing rapidly outside London. Many TB control efforts focus on the capital, but with rates rising elsewhere in the country, this strategy is likely to fail in the long term.
Melanoma immunotherapy using mature DCs expressing the constitutive proteasome
Authors: Jens Dannull, N. Rebecca Haley, Gary Archer, Smita Nair, David Boczkowski, Mark Harper, Nicole De Rosa, Nancy Pickett, Paul J. Mosca, James Burchette, Maria A. Selim, Duane A. Mitchell, John Sampson, Douglas S. Tyler, Scott K. Pruitt
Journal: Journal of Clinical Investigation (2013)

Many cancers, including melanoma, exclusively express constitutive proteasomes (cPs) and are unable to express immunoproteasomes (iPs). In contrast, mature DCs used for immunotherapy exclusively express iPs. Since proteasomes generate peptides presented by HLA class I molecules, we hypothesized that mature melanoma antigen-loaded DCs engineered to process antigens through cPs would be superior inducers of antimelanoma immunity in vivo.Subjects with metastatic melanoma were vaccinated with mature DCs transfected with RNAs encoding melanoma antigens MART1, MAGE-3, gp100, and tyrosinase. These DCs were derived from monocytes that were untransfected (Arm A; n = 4), transfected with control siRNA (Arm B; n = 3), or transfected with siRNAs targeting the 3 inducible iP subunits (Arm C; n = 5).Vaccination stimulated antigen-specific T cell responses in all subjects, which peaked after 3-4 vaccinations, but remained elevated in Arm C subjects. Also in Arm C, circulating melanoma cell levels (as detected by quantitative PCR) fell, and T cell lytic activity against autologous melanoma was induced. In HLA-A2⁺ subjects, CD8⁺ T cells that bound tetramers loaded with cP-derived melanoma antigenic peptides were found in the peripheral blood only in Arm C subjects. Of 2 subjects with active disease (both in Arm C), one had a partial clinical response, while the other, who exhibited diffuse dermal and soft tissue metastases, had a complete response.These results suggest that the efficacy of melanoma DC-based immunotherapy is enhanced when tumor antigen-loaded DCs used for vaccination express cPs.Clinicaltrials.gov NCT00672542.Duke Clinical Research Institute/Duke Translational Medicine Institute, Duke Melanoma Consortium, and Duke University Department of Surgery.
Effect of salbutamol on dynamic hyperinflation in chronic obstructive pulmonary disease patients
Authors: C Tantucci, A Duguet, T Similowski, M Zelter, JP Derenne, J Milic-Emili
Journal: European Respiratory Journal (1998)

Expiratory flow limitation (EFL), which promotes dynamic hyperinflation and increased work of breathing, often occurs in chronic obstructive pulmonary disease (COPD). The purpose of this study was to assess the effect of bronchodilators on EFL and end-expiratory lung volume in patients with moderate-to-severe COPD. EFL was assessed by applying negative expiratory pressure (NEP) at the mouth during tidal expiration. EFL was present when expiratory flow did not increase or increased only in the early phase of expiration with NEP. In 18 patients (age 65+/-2 yrs; forced expiratory volume in one second (FEV1)=45+/-4% predicted) pulmonary function tests and a series of NEP (-3.5 cmH2O) test breaths were performed at rest in a sitting position before and 20 min after inhalation of 400 microg of salbutamol. EFL was detected in 11 patients and persisted after salbutamol in all of these flow-limited (FL) patients. After bronchodilator administration FL patients exhibited a significant decrease in functional residual capacity (FRC) associated with an increase in inspiratory capacity (IC). In contrast, no changes in FRC and IC were observed in the seven non flow-limited (NFL) patients after administration of salbutamol. Except for one NFL patient, the other 17 patients (six NFL and 11 FL) had no reversibility of their bronchial obstruction (delta FEV1 &lt;10% pred). In conclusion, patients with chronic obstructive pulmonary disease and expiratory flow limitation, even if nonresponders in terms of forced expiratory volume in one second, may benefit from bronchodilators because they can breathe, still in a flow-limited manner, at a lower lung volume.
Effect of the Methylenetetrahydrofolate Reductase C677T Polymorphism on Chemosensitivity of Colon and Breast Cancer Cells to 5-Fluorouracil and Methotrexate
Authors: Kyoung-Jin Sohn, Ruth Croxford, Zoe Yates, Mark Lucock, Young-In Kim
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Although single nucleotide polymorphisms may be potentially important pharmacogenetic determinants of cancer therapy, functional evidence regarding their relevance is currently lacking. The C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with changes in cellular composition of folates. We hypothesized that this polymorphism may modulate the cytotoxic effect of 5-fluorouracil (5FU) and methotrexate (MTX), two commonly used chemotherapeutic agents for colon and breast cancers, because the modes of action of 5FU and MTX are critically dependent on cellular composition of folates. Methods: Human HCT116 colon and MDA-MB-435 breast cancer cells were stably transfected with wild-type or mutant 677T human MTHFR cDNA. MTHFR enzyme activity and thermolability, intracellular folate composition, growth rate, and catalytic thymidylate synthase activity were determined. In vitro chemosensitivity to 5FU and MTX was determined using the sulforhodamine B assay. In vivo chemosensitivity of HCT116 cells to 5FU was determined in nude mice. Results: Compared with cells expressing the wild-type MTHFR, HCT116 and MDA-MB-435 cells expressing the mutant 677T MTHFR had decreased MTHFR activity, MTHFR thermolability, changed intracellular folate distribution, accelerated cellular growth rate, and increased thymidylate synthase activity. The MTHFR 677T mutation increased chemosensitivity of colon and breast cancers to 5FU, but decreased chemosensitivity of breast cancer cells to MTX. In nude mice, xenografts expressing the mutant 677T MTHFR grew faster, but were more sensitive to 5FU, than xenografts expressing the wild-type protein. Conclusions: Our data provide evidence that the MTHFR C677T polymorphism affects the concentration and intracellular distribution of folates and changes the growth and chemosensitivity of colon and breast cancer cells. The MTHFR C677T polymorphism may be a useful pharmacogenetic determinant for providing rational and effective tailored chemotherapy.
Toll-like Receptor 9 Activation Is a Key Mechanism for the Maintenance of Chronic Lung Inflammation
Authors: Toshihiro Ito, Matthew Schaller, Tracy Raymond, Amrita D. Joshi, Ana L. Coelho, Fabiani G. Frantz, William F. Carson, Cory M. Hogaboam, Nicholas W. Lukacs, Theodore J. Standiford, Sem H. Phan, Stephen W. Chensue, Steven L. Kunkel
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Accumulating evidence supports the hypothesis that the continuous host response to a persistent challenge can polarize the cytokine environment toward a Th2 cytokine phenotype, but the mechanisms responsible for this skewing are not clear.We investigated the role of Toll-like receptor 9 (TLR9) in a Th2-driven pulmonary granulomatous response initiated via the embolization of Schistosoma mansoni eggs to the lungs of mice.Mice were intravenously injected with S. mansoni eggs. Histological and flow cytometric analysis, cytokine measurement, adoptive transfer of bone marrow (BM)-derived dendritic cells (DCs), and in vitro T-cell treatments with antigen-presenting cells were examined.In comparison to wild-type mice, TLR9(-/-) mice showed increased pulmonary granuloma size, augmented collagen deposition, increased Th2 cytokine phenotype, and impaired accumulation of DCs. BM-derived DCs, but not macrophages, recovered from animals with developed Th2-type lung granulomas promoted the production of type 2 cytokines from CD4(+) T cells. BM-derived DCs from TLR9(-/-) mice induced impaired Th1 cytokine and enhanced Th2 cytokine production by T cells, compared with DCs from WT mice. Macrophages from TLR9(-/-) mice expressed a significantly higher alternatively activated (M2) phenotype characterized by increased "found in inflammatory zone-1" (FIZZ1) and arginase-1 expression. The adoptive transfer of BM-derived DCs from syngeneic WT mice into TLR9(-/-) mice restored the granuloma phenotype seen in WT mice.These studies suggest that TLR9 plays an important mechanistic role in the maintenance of the pulmonary granulomatous response.
Increased level of apolipoprotein B/apolipoprotein A1 ratio as a potential risk for osteonecrosis
Authors: K. Miyanishi, T. Yamamoto, T. Irisa, Y. Noguchi, Y. Sugioka, Y. Iwamoto
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> This study was performed to investigate whether a high ratio of apolipoprotein B to apolipoprotein A1 (apo B/apo A1 ratio) is significantly associated with the risk of developing non-traumatic osteonecrosis of the femoral head (ON). <h3>METHODS</h3> Fifty consecutive non-traumatic ON cases were compared with 50 age and sex matched controls, using both univariate and stepwise discriminant analyses, regarding the factors of corticosteroid, alcohol, cigarettes, cholesterol, triglyceride, and apo B/apo A1 ratio. To eliminate the possibility that ON or osteoarthritic change itself can increase the apo B/apo A1 ratio, a further 32 consecutive cases comprising nine traumatic ON and 23 osteoarthritis (OA) patients were analysed using Scheffe's test. <h3>RESULTS</h3> There was a significant association between a high apo B/apo A1 ratio and the development of non-traumatic ON with both univariate (p=0.0001) and stepwise discriminant analyses (partial<i>r</i><sup>2</sup>=0.1239, p=0.0004). The apo B/apo A1 ratio in the non-traumatic ON group was significantly higher than that in the traumatic ON (p&lt;0.01), control (p&lt;0.001), or the OA groups (p&lt;0.001). <h3>CONCLUSION</h3> A high apo B/apo A1 ratio is significantly associated with the risk of developing ON. This ratio may be useful for assessing the potential risk of developing osteonecrosis.
ELECTROENCEPHALOGRAPHIC STUDIES IN DELINQUENT BEHAVIOR PROBLEM CHILDREN
Authors: NORMAN Q. BRILL, HERTA SEIDEMANN, HELEN MONTAGUE, BEN H. BALSER
Journal: American Journal of Psychiatry (1942)

1. Electroencephalographic examinations were performed on 28 children who had been brought before the Domestic Relations Court of the City of New York. 2. In 61 per cent of the entire group, the brain potentials suggested an underlying disorder in brain function. When only those with behavior disorders were considered, 74 per cent showed abnormal activity. 3. These findings, which are similar to those found by other investigators, suggest the presence of an underlying cerebral disorder in a majority of children with severe behavior disorders. [See Source PDF for the Illustrations]
THE ABSORPTION OF FATS STUDIED IN A CHILD WITH CHYLOTHORAX
Authors: J. Fernandes, J. H. Van De Kamer, H. A. Weijers
Journal: Journal of Clinical Investigation (1955)

The quintessence of Verzar's theory is: complete hydrolysis of fat in the intestine and synthesis of the fatty acids to triglycerides in the intestinal cells, via an intermediate stage of phospholipids. The main features of Frazer's theory are: hydrolysis of part of the fat into mono- and diglycerides and free fatty acids in the intestine,