tbuckley/cabot-search huggingface dataset:
Pulmonary Hypertension as a Risk Factor for Death in Patients with Sickle Cell Disease
Authors: Mark T. Gladwin, Vandana Sachdev, Maria L. Jison, Yukitaka Shizukuda, Jonathan F. Plehn, Karin Minter, Bernice Brown, Wynona A. Coles, James S. Nichols, Inez Ernst, Lori A. Hunter, William C. Blackwelder, Alan N. Schechter, Griffin P. Rodgers, Oswaldo Castro, Frederick P. Ognibene
Journal: New England Journal of Medicine (2004)

The prevalence of pulmonary hypertension in adults with sickle cell disease, the mechanism of its development, and its prospective prognostic significance are unknown.We performed Doppler echocardiographic assessments of pulmonary-artery systolic pressure in 195 consecutive patients (82 men and 113 women; mean [+/-SD] age, 36+/-12 years). Pulmonary hypertension was prospectively defined as a tricuspid regurgitant jet velocity of at least 2.5 m per second. Patients were followed for a mean of 18 months, and data were censored at the time of death or loss to follow-up.Doppler-defined pulmonary hypertension occurred in 32 percent of patients. Multiple logistic-regression analysis, with the use of the dichotomous variable of a tricuspid regurgitant jet velocity of less than 2.5 m per second or 2.5 m per second or more, identified a self-reported history of cardiovascular or renal complications, increased systolic blood pressure, high lactate dehydrogenase levels (a marker of hemolysis), high levels of alkaline phosphatase, and low transferrin levels as significant independent correlates of pulmonary hypertension. The fetal hemoglobin level, white-cell count, and platelet count and the use of hydroxyurea therapy were unrelated to pulmonary hypertension. A tricuspid regurgitant jet velocity of at least 2.5 m per second, as compared with a velocity of less than 2.5 m per second, was strongly associated with an increased risk of death (rate ratio, 10.1; 95 percent confidence interval, 2.2 to 47.0; P<0.001) and remained so after adjustment for other possible risk factors in a proportional-hazards regression model.Pulmonary hypertension, diagnosed by Doppler echocardiography, is common in adults with sickle cell disease. It appears to be a complication of chronic hemolysis, is resistant to hydroxyurea therapy, and confers a high risk of death. Therapeutic trials targeting this population of patients are indicated.
Rescue of Cell-Transforming Virus From a Non-Virus-Producing Bovine Cell Culture Transformed by Feline Sarcoma Virus
Authors: Emerson W. Chan, Pauline E. Schiop-Stansly, Timothy E. O'Connor
Journal: JNCI Journal of the National Cancer Institute (1974)

A fully and stably transformed but non-virusproducing cell culture was derived from a single focus of transformed cells in a bovine embryonic trachea cell culture infected with a terminal dilution of Snyder-Theilen feline sarcoma virus. However, cell-transforming virus was rescued from this non-virus-producing culture, both by superinfection with feline helper viruses and by induction with 5-iodo-2'-deoxyuridine. The chemically induced virus was antigenically related to feline leukemia virus but exhibited an altered host range.
A phase I and pharmacokinetic study of irinotecan in patients with hepatic or renal dysfunction or with prior pelvic radiation: CALGB 9863
Authors: A.P. Venook, C. Enders Klein, G. Fleming, D. Hollis, C.G. Leichman, R. Hohl, J. Byrd, D. Budman, M. Villalona, J. Marshall, G.L. Rosner, J. Ramirez, H. Kastrissios, M.J. Ratain
Journal: Annals of Oncology (2003)
Aetiology of unresolved pneumonia.
Authors: S R Bulmer, D Lamb, R J McCormack, P R Walbaum
Journal: Thorax (1978)

Preoperative histological or cytological confirmation of a diagnosis of bronchogenic carcinoma is not always possible, so occasionally non-neoplastic lesions are resected. Of these lesions a significant number are described by pathologists as 'unresolved pneumonia'. We studied the case notes and histopathology of 30 patients from whom lung had been resected and which had been classified as pneumonia. Other non-neoplastic lesions, such as pulmonary infarction, bronchiectasis, and tuberculosis, were excluded. All had a preoperative diagnosis of probable bronchial carcinoma. On review very few appeared to be the consequence of an infective, pneumonic episode. In 11, foreign material was identified, including one typical example of a paraffinoma. Aspiration of foreign material may lead to a localised lesion which simulates carcinoma of the bronchus both clinically and radiographically.
Modulation of Interferon-Induced Genes by Lipoxin Analogue in Anti–Glomerular Basement Membrane Nephritis
Authors: Takamoto Ohse, Tatsuru Ota, Niamh Kieran, Catherine Godson, Koei Yamada, Tetsuhiro Tanaka, Toshiro Fujita, Masaomi Nangaku
Journal: Journal of the American Society of Nephrology (2004)

Immune complex deposition is associated with the accumulation of neutrophils, which play an important role in the various immune-mediated diseases. A novel anti-inflammatory agent, the lipoxin A (LXA) analogue (15-epi-16-(FPhO)-LXA-Me)), a stable synthetic analogue of aspirin-triggered 15-epi-lipoxin A4 (ATLa), was used in experimental anti-glomerular basement membrane (GBM) antibody nephritis in mice. ATLa was administered before the induction of the disease, and 2 h later, the animals were killed. ATLa reduced the infiltrating neutrophils and nitrotyrosine staining in glomeruli. Subsequent changes of gene expression in the early phase were evaluated, and 5674 genes were present under the basal conditions in kidneys from normal mice; 54 upregulated genes and 25 downregulated genes were detected in anti-GBM nephritis. Eighteen of these upregulated genes were those induced by IFN-gamma. Real-time quantitative PCR analysis confirmed the results of the microarrays. To investigate a role of IFN-gamma in neutrophil infiltration, anti-GBM nephritis was induced in IFN-gamma knockout mice. The number of infiltrating neutrophils in these mice did not differ from those in wild-type mice. Also examined were CD11b expression on neutrophils from mice treated with ATLa by flow cytometry, but suppression of this adhesion molecule was not observed. Neutrophil infiltration was successfully inhibited by ATLa in the early phase of murine anti-GBM nephritis. Microarray analysis detected the change of mRNA expression in anti-GBM nephritis and demonstrated amelioration of various genes by ATLa, which may provide a clue to the development of novel therapeutic approaches in immune renal injury.
A Novel Transforming Growth Factor β Receptor Kinase Inhibitor, A-77, Prevents the Peritoneal Dissemination of Scirrhous Gastric Carcinoma
Authors: Hidemi Kawajiri, Masakazu Yashiro, Osamu Shinto, Kazunori Nakamura, Masashige Tendo, Satoru Takemura, Manabu Node, Yoshio Hamashima, Tetsuya Kajimoto, Tetsuji Sawada, Masaichi Ohira, Kosei Hirakawa
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Transforming growth factor β receptor (TGFβ-R) is reported to correlate with the malignant potential of scirrhous gastric carcinoma. The aim of the current study is to clarify the possibility of molecular target therapy with a TGFβ-R inhibitor, A-77, for the treatment of peritoneal dissemination of scirrhous gastric cancer. Experimental Design: Three scirrhous gastric cancer cell lines and two fibroblasts were used. For in vivo experiments, the A-77 was administered i.p. to mouse models of peritoneal dissemination. The influences of A-77 on the adhesion ability, invasion ability, and the expression of adhesion molecules were examined in vitro. Results: The A-77 administration resulted in a significantly (P &amp;lt; 0.01) better prognosis for the mice with peritoneal dissemination (median survival time, 51 days), compared with the control (median survival time, 25 days). A-77 therefore significantly (P &amp;lt; 0.01) decreased the weight and number of metastatic nodes. The adhesive ability and invasion ability of cancer cells were significantly decreased by A-77. A-77 decreased the expression of α2, α3, and α5 integrins in gastric cancer cells. The histologic findings showed the degree of fibrosis to be less in the tumors treated by A-77. A-77 decreased the growth of fibroblast and invasion-stimulating activity of fibroblasts on cancer cells. Conclusion: The TGFβ-R inhibitor, A-77, decreased the expression of integrins in cancer cells and the proliferation of fibroblasts, which resulted in the decreased adhesive and invasive abilities of scirrhous gastric cancer cells to peritoneum. A-77 is thus considered to be useful for the inhibition of peritoneal dissemination of scirrhous gastric carcinoma.
Unsuspected Venous Alkalemia
Authors: S. Raymond Gambino
Journal: JAMA (1966)

UNSUSPECTED venous alkalemia suggests serious intra-abdominal or intracerebral disease. This laboratory syndrome is characterized by an alkaline venous pH (greater than 7.50); a slightly decreased carbon dioxide pressure (Pco<sub>2</sub>), between 29 and 35 mm Hg; a slightly increased base excess (between +4 and +8); and a normal carbon dioxide content of bicarbonate level. I have called this syndrome "unsuspected alkalemia" because the carbon dioxide content is normal. If carbon dioxide or content combining power or bicarbonate level were used as the sole indicator of acid-base disturbance, these cases would remain undetected. <h3>Observations</h3> A review of 4,151 complete venous acid-base studies performed in our laboratory on specimens from 1,650 patients revealed the clinical importance of unsuspected venous alkalemia. Complete acid-base studies (pH, Pco<sub>2</sub>, base excess, carbon dioxide content, sodium, potassium, and chloride) were performed routinely in any patient whose blood was drawn for<i>any</i>electrolyte study. Of the 4,151
Escherichia coli hemolysin is a potent inductor of phosphoinositide hydrolysis and related metabolic responses in human neutrophils.
Authors: F Grimminger, U Sibelius, S Bhakdi, N Suttorp, W Seeger
Journal: Journal of Clinical Investigation (1991)

Escherichia coli hemolysin (Hly) is a proteinaceous pore-forming exotoxin that probably represents a significant virulence factor in E. coli infections. We investigated its influence on human polymorphonuclear neutrophils (PMN), previously identified as highly susceptible targets. Hly provoked rapid secretion of elastase and myeloperoxidase, generation of superoxide, and synthesis of platelet-activating factor (PAF) and lyso-PAF. Concomitantly, marked phosphatidylinositol (PtdIns) hydrolysis with sequential appearance of the inositol-phosphates, inositol-phosphates, inositol triphosphate, diphosphate, and monophosphate, respectively, and formation of diacylglycerol, occurred. The metabolic responses displayed distinct bell-shaped dose dependencies, with maximum events noted at low toxin concentrations of 0.1-0.5 hemolytic units per milliliter. PtdIns hydrolysis and metabolic responses elicited by Hly exceeded those evoked by optimal concentrations of formylmethionyl-leucyl phenylalanine, PAF, leukotriene B4, A23187, or staphylococcal alpha-toxin. The toxin-induced effects were sensitive toward modulators of PMN stimulus transmission pathways (pertussis toxin, the kinase C inhibitor H7, and phorbol myristate acetate "priming"). We conclude that the marked capacity of low doses of Hly to elicit degranulation, respiratory burst, and lipid mediator generation in human PMN probably envolves signal transduction via PtdIns hydrolysis.
Imatinib mesylate inhibits in vitro and ex vivo biological responses related to vascular occlusion in giant cell arteritis
Authors: E Lozano, M Segarra, A Garcia-Martinez, J Hernandez-Rodriguez, M C Cid
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> Ischaemic complications occur in 15–20% of patients with giant cell arteritis (GCA). The aim of our study was to explore the effect of mesenchymal growth factors expressed in GCA lesions on myointimal cell responses related to the development of intimal hyperplasia and vessel occlusion. <h3>Methods:</h3> We developed a method to obtain primary human temporal artery derived myointimal cells (HTAMCs) based on the culture of temporal artery sections on Matrigel. <h3>Results:</h3> Among the factors tested (platelet-derived growth factor (PDGF)-AB, fibroblast growth factor (FGF)-2, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), transforming growth factor (TGF)β, chemokine (C-C motif) ligand (CCL)2, interleukin (IL)6 and IL1β), PDGF exhibited the strongest activity in inducing HTAMC proliferation and migration. As assessed by protein array, immunoassay and quantitative real-time reverse transcriptase (RT)-PCR, PDGF stimulated matrix proteins (collagen I, collagen III and fibronectin) as well as CCL2 and angiogenin production by HTAMCs. Imatinib mesylate inhibited PDGF-mediated activation of signalling pathways (Src, extracellular signal-regulated kinase (ERK) and Akt phosphorylation) related to cell motility and survival, efficiently resulting in inhibition of PDGF-induced HTAMC responses. Myointimal cell outgrowth from cultured temporal artery sections from patients with GCA, where multiple interactions take place, was also efficiently reduced by imatinib. <h3>Conclusion:</h3> Among several mediators produced in GCA, PDGF has the highest vaso-occlusive potential. PDGF may also contribute to disease perpetuation by stimulating the production of angiogenic factors (angiogenin) and chemoattractants (CCL2). Imatinib mesylate strongly inhibits PDGF-mediated responses, suggesting a therapeutic potential to limit vascular occlusion and ischaemic complications in large vessel vasculitis.
IgG subclass deficiencies associated with bronchiectasis.
Authors: J De Gracia, M J Rodrigo, F Morell, M Vendrell, M Miravitlles, M J Cruz, R Codina, J M Bofill
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Only a small number of patients with IgG subclass deficiencies (IgGSD) have been observed to have bronchiectasis. Moreover, in the series of patients with bronchiectasis, IgGSD have not been found at any frequency, and the etiology of bronchiectasis remains unclear in 29 to 49% of cases. Serum concentrations of total IgG, IgA, and IgG subclasses as well as pulmonary function were measured in 65 patients (aged: 10 to 74 yr) with bronchiectasis of unknown etiology. An ELISA test was performed to quantify subclasses 1 through 4 using subclass-specific antihuman monoclonal antibodies. IgG subclass estimation in a healthy population with age-stratified normal ranges was derived from 100 adults, 37 children aged between 10 and 12 yr, and 27 adolescents aged between 13 and 16 yr. Serum concentrations of specific IgG antibodies to Haemophilus influenzae type b capsular polysaccharide (Hib-PRP) were also assayed by an ELISA test in 19 of the patients (10 with IgGSD and nine with non-IgGSD) and in 58 healthy individuals before and 3 wk after immunization with Hib-PRP conjugated to meningococcal outer membrane protein complex (OMPC). Thirty-one patients (48%) had low serum concentrations of one or more IgG subclasses (19 IgG2 deficiencies, 2 IgG3 deficiencies, 3 IgG4 deficiencies, and 7 combined subclass deficiencies). All patients showed increased levels of total IgG, IgG1, and IgA, but this rise was significantly higher in patients without IgGSD. Patients with IgGSD showed impaired antibody response to Hib-PRP compared with patients with non-IgGSD and the control group. IgGSD, particularly IgG2 deficiency, are not an unusual cause of bronchiectasis. Therefore, serum levels of IgG subclasses must be assayed whenever other causes of bronchiectasis have been ruled out.
Recovery From 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced Immunosuppression in A/J Mice by Treatment With Nonsteroidal Antiinflammatory Drugs
Authors: N. Rioux, A. Castonguay, D. Hoffmann
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: We have previously reported that nonsteroidal anti-inflammatory drugs inhibit lung tumorigenesis induced by the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mice. Purpose: The aims of this study were to determine if NNK suppresses humoral (i.e., antibody) and cellular immune responses in mice and if nonsteroidal anti-inflammatory drugs could attenuate these immune responses. Methods: Female A/J mice (7-8 weeks old) were fed nonsteroidal anti-inflammatory drugs starting 2 weeks before the beginning of NNK treatment (9.1 mg per mouse in total) and continuing through the 7 weeks of NNK treatment. Eight groups (two control groups and six experimental groups) of 10 mice each were used per experiment. Animals in the two control groups received the same diet and water as animals in the six experimental groups; one control group received no nonsteroidal antiinflammatory drugs or NNK and the other control group received only NNK. The primary humoral and cellular immune responses to the various treatments were assayed by the plaqueforming cell technique and by measurement of natural killer cell cytotoxic activity, respectively. At the end of each experiment, the animals were killed, blood was collected, plasma was prepared, and levels of the immune system modulator prostaglandin E2 were measured. Results: NNK treatment inhibited the plaque-forming cell response by approximately 50%; this inhibition was attenuated by treatment with sulindac or acetylsalicylic acid ( P = .0001 for both). In contrast, treatment with naproxen, which had no chemopreventive (i.e., tumor inhibitory) efficacy, further increased by 26% ( P = .05) the immunosuppressive effect of NNK. The cytotoxic activity of splenic natural killer cells against YAC-1 cells was reduced by 60% ( P = .002); treatment with acetylsalicylic acid (254 mg/kg of diet) reduced the NNK-induced natural killer cell cytotoxicity inhibition by 50% ( P = .02), whereas the administration of the specific cyclooxygenase-2 inhibitor NS-398 (7 mg/kg of diet) resulted in an almost complete recovery (approximately 95%, P = .04) of natural killer cell activity. The prostaglandin E 2 plasma concentration was approximately 100% greater in NNKtreated mice than in untreated mice. Treatment of the mice with nonsteroidal anti-inflammatory drugs attenuated this elevation (from approximately 25% to 100%), and NS-398 (7 mg/kg of diet) was the most effective (100%). Conclusions and Implications: The ability of various nonsteroidal anti-inflammatory drugs to inhibit NNK-induced carcinogenesis appears to be directly related to the ability of these drugs to inhibit NNK-induced immunosuppression. Our results suggest that the chemopreventive effect of nonsteroidal anti-inflammatory drugs may be mediated through the modulation of prostaglandin E 2 synthesis.
834-6 Identification of cardiac sarcoidosis from the patients presenting as unexplained heart failure and cardiomyopathies
Authors: Osamu Yokoseki, Yoshikazu Yazaki, Kaoru Kogashi, Takeshi Hanaoka, Yuichi Kai, Osamu Kinoshita, Minoru Hongo, Keishi Kubo, Morie Sekiguchi
Journal: Journal of the American College of Cardiology (2004)
Residential Versus Community Treatment of Personality Disorders: A Comparative Study of Three Treatment Programs
Authors: Marco Chiesa, Peter Fonagy, Jeremy Holmes, Carla Drahorad
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The aim of this study was to compare the effectiveness of three treatment models for personality disorder: 1) a long-term psychoanalytically oriented residential specialist program, 2) a phased "step-down" specialist psychosocial program that included a briefer residential stay and an outpatient component, and 3) a general community psychiatric model. METHOD: One hundred forty-three patients with a personality disorder diagnosis were allocated according to geographical criteria to the three treatment conditions. Outcome was prospectively evaluated at 6, 12, and 24 months through the use of a standardized battery of instruments that included measures of general symptom severity, social adaptation, assessment of mental health functioning, frequency of self-harm and suicide attempts, and rates and duration of hospital readmissions. RESULTS: By 24 months, patients in the step-down condition showed significant improvements on all measures. Patients in the long-term residential model showed significant improvements in symptom severity, social adaptation, and global functioning, while no changes were achieved in self-harm, attempted suicide, and readmission rates. Patients in the general psychiatric group showed no improvement on any variables except self-harm and hospital readmissions. CONCLUSIONS: The results of this study suggest that for personality disorders, a specialist step-down program is more effective than both long-term residential treatment and general psychiatric treatment in the community. Replication is needed that includes a random allocation of patients to conditions to ensure that geographical factors did not account for the observed differences.
Outcomes of Screening Mammography by Frequency, Breast Density, and Postmenopausal Hormone Therapy
Authors: Karla Kerlikowske, Weiwei Zhu, Rebecca A. Hubbard, Berta Geller, Kim Dittus, Dejana Braithwaite, Karen J. Wernli, Diana L. Miglioretti, Ellen S. O’Meara, for the Breast Cancer Surveillance Consortium
Journal: JAMA Internal Medicine (2013)

Controversy exists about the frequency women should undergo screening mammography and whether screening interval should vary according to risk factors beyond age.To compare the benefits and harms of screening mammography frequencies according to age, breast density, and postmenopausal hormone therapy (HT) use.Prospective cohort.Data collected January 1994 to December 2008 from mammography facilities in community practice that participate in the Breast Cancer Surveillance Consortium (BCSC) mammography registries.Data were collected prospectively on 11,474 women with breast cancer and 922,624 without breast cancer who underwent mammography at facilities that participate in the BCSC.We used logistic regression to calculate the odds of advanced stage (IIb, III, or IV) and large tumors (>20 mm in diameter) and 10-year cumulative probability of a false-positive mammography result by screening frequency, age, breast density, and HT use. The main predictor was screening mammography interval.Mammography biennially vs annually for women aged 50 to 74 years does not increase risk of tumors with advanced stage or large size regardless of women's breast density or HT use. Among women aged 40 to 49 years with extremely dense breasts, biennial mammography vs annual is associated with increased risk of advanced-stage cancer (odds ratio [OR], 1.89; 95% CI, 1.06-3.39) and large tumors (OR, 2.39; 95% CI, 1.37-4.18). Cumulative probability of a false-positive mammography result was high among women undergoing annual mammography with extremely dense breasts who were either aged 40 to 49 years (65.5%) or used estrogen plus progestogen (65.8%) and was lower among women aged 50 to 74 years who underwent biennial or triennial mammography with scattered fibroglandular densities (30.7% and 21.9%, respectively) or fatty breasts (17.4% and 12.1%, respectively).Women aged 50 to 74 years, even those with high breast density or HT use, who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of false-positive results than those who undergo annual mammography. When deciding whether to undergo mammography, women aged 40 to 49 years who have extremely dense breasts should be informed that annual mammography may minimize their risk of advanced-stage disease but the cumulative risk of false-positive results is high.