tbuckley/cabot-search huggingface dataset:
Localization of T and B cells and alpha fetoprotein in hepatic biopsies from patients with liver disease.
Authors: G Husby, R G Strickland, J L Caldwell, R C Williams
Journal: Journal of Clinical Investigation (1975)

Peripheral blood and hepatic tissue T- and B-lymphocyte distributions, serum alpha fetoprotein (AFP) concentrations, and hepatic AFP were studied in 46 patients undergoing diagnostic percutaneous liver biopsy. The patients included 26 with alcoholic liver disease, 13 with nonalcoholic hepatitis or cirrhosis, and 7 with either normal histology or minor nonspecific changes. Serum AFP was determined by radioimmunoassay and hepatic tissue AFP by indirect immunofluorescence. Peripheral blood T lymphocytes were identified by the sheep red-cell rosette technique; and B lymphocytes by fluoresceinated anti-immunoglobulin antisera and IgG aggregates. Tissue identification of T lymphocytes was accomplished using an extensively absorbed rabbit antihuman thymocyte antiserum and indirect immunofluorescence; tissue B lymphocytes were identified using pepsin F (ab')2 fragments of rabbit IgG antibodies to human immunoglobulins. T lymphocytes predominanted in hepatic lymphoid infiltrates from patients with alcoholic liver disease (91+/-4%), whereas in patients with chronic active or chronic persistant hepatitis, viral hepatitis, or cryoptogenic cirrhosis proportions of T and B lymphocytic infiltrates were similar (50+/-15%). Hepatic tissue AFP was detected in 9 of 18 patients with alcoholic hepatitis; serum AFP concentration was increased in only 1 of these 9 patients. Tissue AFP was not observed in the remaining biopsy material nor were serum AFP concentrations increased. Peripheral blood T-cell numbers were significantly decreased in patients with alcoholic liver disease (P less than 0.01) and in nonalcoholic hepatitis or cirrhosis (P less than 0.025). A close relationship between peripheral blood T-lymphocytopenia and hepatic T-cell infiltrates was observed in patients with alcoholic liver disease; this relationship was less apparent in patients with nonalcoholic hepatitis or cirrhosis.
Oxidized LDL Promotes Peroxide-Mediated Mitochondrial Dysfunction and Cell Death in Human Macrophages
Authors: Reto Asmis, Jim G. Begley
Journal: Circulation Research (2003)

Several studies suggest that macrophage death and subsequent lysis contribute to the development of advanced atherosclerotic lesions. Although oxidized LDL (OxLDL) is thought to contribute to lesion formation and induces macrophage apoptosis, the mechanisms underlying macrophage lysis have not been well defined. To determine if induction of apoptosis in human macrophages also promotes cell lysis, we studied caspase-3 activation by OxLDL and activating anti-Fas antibodies. We found that Fas-induced activation of caspase-3 does not promote macrophage lysis and caspase-3 activation is not required for OxLDL-induced macrophage lysis. OxLDL induces the formation of peroxides, but not superoxide, and decreases mitochondrial membrane potential. Scavengers of peroxyl radicals restore mitochondrial membrane potential and prevent macrophage lysis, implicating peroxyl radicals in both mitochondrial dysfunction and macrophage lysis induced by OxLDL. We conclude that macrophage death induced by OxLDL results in cell lysis, but it does not require activation of Fas or caspase-3. The full text of this article is available at http://www.circresaha.org.
Treatment of Acute Hypoxemic Nonhypercapnic Respiratory Insufficiency With Continuous Positive Airway Pressure Delivered by a Face Mask
Authors: C Delclaux, E L'Her, C Alberti, J Mancebo, F Abroug, G Conti, C Guérin, F Schortgen, Y Lefort, M Antonelli, E Lepage, F Lemaire, L Brochard
Journal: JAMA (2000)

ContextContinuous positive airway pressure (CPAP) is widely used in the belief that it may reduce the need for intubation and mechanical ventilation in patients with acute hypoxemic respiratory insufficiency.ObjectiveTo compare the physiologic effects and the clinical efficacy of CPAP vs standard oxygen therapy in patients with acute hypoxemic, nonhypercapnic respiratory insufficiency.Design, Setting, and PatientsRandomized, concealed, and unblinded trial of 123 consecutive adult patients who were admitted to 6 intensive care units between September 1997 and January 1999 with a PaO2/FIO2 ratio of 300 mm Hg or less due to bilateral pulmonary edema (n = 102 with acute lung injury and n = 21 with cardiac disease).InterventionsPatients were randomly assigned to receive oxygen therapy alone (n = 61) or oxygen therapy plus CPAP (n = 62).Main Outcome MeasuresImprovement in PaO2/FIO2 ratio, rate of endotracheal intubation at any time during the study, adverse events, length of hospital stay, mortality, and duration of ventilatory assistance, compared between the CPAP and standard treatment groups.ResultsAmong the CPAP vs standard therapy groups, respectively, causes of respiratory failure (pneumonia, 54% and 55%), presence of cardiac disease (33% and 35%), severity at admission, and hypoxemia (median [5th-95th percentile] PaO2/FIO2 ratio, 140 [59-288] mm Hg vs 148 [62-283] mm Hg; P = .43) were similarly distributed. After 1 hour of treatment, subjective responses to treatment (P<.001) and median (5th-95th percentile) PaO2/FIO2 ratios were greater with CPAP (203 [45-431] mm Hg vs 151 [73-482] mm Hg; P = .02). No further difference in respiratory indices was observed between the groups. Treatment with CPAP failed to reduce the endotracheal intubation rate (21 [34%] vs 24 [39%] in the standard therapy group; P = .53), hospital mortality (19 [31%] vs 18 [30%]; P = .89), or median (5th-95th percentile) intensive care unit length of stay (6.5 [1-57] days vs 6.0 [1-36] days; P = .43). A higher number of adverse events occurred with CPAP treatment (18 vs 6; P = .01).ConclusionIn this study, despite early physiologic improvement, CPAP neither reduced the need for intubation nor improved outcomes in patients with acute hypoxemic, nonhypercapnic respiratory insufficiency primarily due to acute lung injury.
Heterozygosity for Roquinsan leads to angioimmunoblastic T-cell lymphoma-like tumors in mice
Authors: Julia I. Ellyard, Tiongsun Chia, Socorro-Maria Rodriguez-Pinilla, Jaime L. Martin, Xin Hu, Manuel Navarro-Gonzalez, Juan F. Garcia, Marie-Helene Delfau-Larue, Santiago Montes-Moreno, Philippe Gaulard, Matthew C. Cook, Giles Walters, Miguel A. Piris, Carola G. Vinuesa
Journal: Blood (2012)
Cryptogenetic multifocal ulcerous stenosing enteritis: an atypical type of vasculitis or a disease mimicking vasculitis
Authors: G Perlemuter
Journal: Gut (2001)

Cryptogenetic multifocal ulcerous stenosing enteritis (CMUSE) is a rare disease whose origin is unknown. The aim of this study was to describe the clinical spectrum of CMUSE, to determine the origin and pathophysiology of the disease, and to propose a treatment strategy.A total of 220 French gastroenterology departments were contacted to review patients with unexplained small bowel strictures. Of 17 responses, 12 corresponded to a diagnosis of CMUSE. These patients were hospitalised between 1965 and 1993 and their medical records were reviewed.All patients (mean age 42.1 (4.4) years) had intestinal and five had extraintestinal symptoms (peripheral neuropathy, buccal aphthae, sicca syndrome, polyarthralgia, Raynaud's phenomenon, arterial hypertension). One patient had heterozygous type I C2 deficiency (28 base pair gene deletion). Two to 25 (mean 8.3 (1.9)) small intestine strictures were found. Stenoses of the large jejunoileal arteries were observed on two and aneurysms on three of five mesenteric angiograms. Despite surgery, symptoms recurred in seven of 10 patients and strictures in four. Steroid therapy was effective but caused dependence. One untreated patient died. Small bowel pathology showed superficial ulceration of the mucosae and submucosae, and an inflammatory infiltrate made of neutrophils and eosinophils.CMUSE is an independent entity characterised by steroid sensitive inflammation of the small bowel which often recurs after surgery. CMUSE may be related to a particular form of polyarteritis nodosa with mainly intestinal expression or with an as yet unclassified vasculitis.
FoxM1 Inhibition Sensitizes Resistant Glioblastoma Cells to Temozolomide by Downregulating the Expression of DNA-Repair Gene <i>Rad51</i>
Authors: Nu Zhang, Xinjian Wu, Lixuan Yang, Feizhe Xiao, Heng Zhang, Aidong Zhou, Zhengsong Huang, Suyun Huang
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Recurrent glioblastoma multiforme (GBM) is characterized by resistance to radiotherapy and chemotherapy and a poor clinical prognosis. In this study, we investigated the role of the oncogenic transcription factor FoxM1 in GBM cells' resistance to alkylator temozolomide (TMZ) and its potential molecular mechanism. Experimental Design: FoxM1 expression levels were measured by immunohistochemical analysis in 38 pairs of primary and recurrent GBM tumor samples. Expression levels were also measured in primary recurrent GBM cell lines, and their responses to TMZ were characterized. In a mechanistic study, an siRNA array was used to identify downstream genes, and a chromatin immunoprecipitation assay was used to confirm transcriptional regulation. Results: Recurrent tumors that were TMZ resistant expressed higher levels of FoxM1 than did primary tumors. Recurrent GBM cell lines expressed higher levels of FoxM1 and the DNA damage repair gene Rad51 and were resistant to TMZ. TMZ treatment led to increased FoxM1 and Rad51 expression. FoxM1 knockdown inhibited Rad51 expression and sensitized recurrent GBM cells to TMZ cytotoxicity. FoxM1 directly regulated Rad51 expression through 2 FoxM1-specific binding sites in its promoter. Rad51 reexpression partially rescued TMZ resistance in FoxM1-knockdown recurrent GBM cells. A direct correlation between FoxM1 expression and Rad51 expression was evident in recurrent GBM tumor samples. Conclusion: Targeting the FoxM1-Rad51 axis may be an effective method to reverse TMZ resistance in recurrent GBM. Clin Cancer Res; 18(21); 5961–71. ©2012 AACR.
TRANSILLUMINATION OF THE ANTRUM OF HIGHMORE
Authors: A. B. Kelly
Journal: BMJ (1905)

MARCH 25, 1 9 0 5 O Still more recent experiments have shown how these two ,opposite sets of results may be reconciled.From these it appears that the early effect of both anaesthetics, lasting up to the period of complete insensibility, is ordinarily an increase of the secretion of urine.This, as a rule, is more pronounced in the case of ether than of chloroform.But during full anaesthesia, however prolonged-and this is the remarkable result-the secretion of urine i8 almost com- petely arrested.By full anaesthesia I mean a degree just beyond the loss of conjunctival reflex-namely, that required in surgical operations.The depressing effect during this period appears likewise to be more pronounced with ether ithan with chloroform.Upon removal of the anaesthetic the kidneys rapidly recover, and, at all events in dogs, are actively secreting once more within five or ten minutes, this activity passing on to a condition of hyperactivity which lasts for some hours.The value of the foregoing results (obtained with dogs) has been greatly enhanced by corroboration from the clinical side.,Observations on renal activity during surgical anaesthesia, -kindly carried out in Mercer's Hospital by Mr. Maunsell and
Active Surveillance in Men With Localized Prostate Cancer
Authors: Issa J. Dahabreh
Journal: Annals of Internal Medicine (2012)

Active surveillance (AS) and watchful waiting (WW) have been proposed as management strategies for low-risk, localized prostate cancer.To systematically review strategies for observational management of prostate cancer (AS or WW), factors affecting their utilization, and comparative effectiveness of observational management versus immediate treatment with curative intent.MEDLINE and Cochrane databases (from inception to August 2011).Screened abstracts and reviewed full-text publications to identify eligible studies.One reviewer extracted data, and another verified quantitative data. Two independent reviewers rated study quality and strength of evidence for comparative effectiveness.Sixteen independent cohorts defined AS, 42 studies evaluated factors that affect the use of observational strategies, and 2 evidence reports and 22 recent studies reported comparisons of WW versus treatment with curative intent. The most common eligibility criteria for AS were tumor stage (all cohorts), Gleason score (12 cohorts), prostate-specific antigen (PSA) concentration (10 cohorts), and number of biopsy cores positive for cancer (8 cohorts). For monitoring, studies used combinations of periodic PSA testing (all cohorts), digital rectal examination (14 cohorts), and rebiopsy (14 cohorts). Predictors of receiving no active treatment included older age, comorbid conditions, lower Gleason score, tumor stage, PSA concentration, and favorable risk group. No published studies compared AS with immediate treatment with curative intent. Watchful waiting was generally less effective than treatment with curative intent; however, applicability to contemporary patients may be limited.Active surveillance and WW often could not be differentiated in the reviewed studies. Published randomized trials have assessed only WW and did not enroll patients diagnosed by PSA screening.Evidence is insufficient to assess whether AS is an appropriate option for men with localized prostate cancer. A standard definition of AS that clearly distinguishes it from WW is needed to clarify scientific discourse.Agency for Healthcare Research and Quality.
Insulin enhances metabolic capacities of cancer cells by dual regulation of glycolytic enzyme pyruvate kinase M2
Authors: Mohd Askandar Iqbal, Farid Ahmad Siddiqui, Vibhor Gupta, Shilpi Chattopadhyay, Prakasam Gopinath, Bhupender Kumar, Siddharth Manvati, Noor Chaman, Rameshwar NK Bamezai
Journal: Molecular Cancer (2013)

Abstract Background Insulin is tightly associated with cancer progression; however, mechanistic insights into such observations are poorly understood. Recent studies show that metabolic transformation is critical to cancer cell proliferation. Here, we attempt to understand the role of insulin in promotion of cancer metabolism. To this end, the role of insulin in regulating glycolytic enzyme pyruvate kinase M2 (PKM2) was examined. Results We observed that insulin up-regulated PKM2 expression, through PI3K/mTOR mediated HIF1α induction, but significantly reduced PKM2 activity independent of this pathway. Drop in PKM2 activity was attributed to subunit dissociation leading to formation of low activity PKM2 oligomers, as assessed by density gradient centrifugation. However, tyrosine 105 phosphorylation of PKM2, known for inhibiting PKM2 activity, remained unaffected on insulin treatment. Interestingly, insulin-induced ROS was found responsible for PKM2 activity reduction. The observed changes in PKM2 status led to augmented cancer metabolism. Insulin-induced PKM2 up-regulation resulted in enhanced aerobic glycolysis as confirmed by PKM2 knockdown studies. Further, PKM2 activity reduction led to characteristic pooling of glycolytic intermediates and increased accumulation of NADPH; suggesting diversion of glucose flux towards macromolecular synthesis, necessary for cancer cell growth. Conclusion The study identifies new PKM2-mediated effects of insulin on cancer metabolism, thus, advancing the understanding of insulin’s role in cancer.
Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis
Authors: Luis Ruiz-del-Arbol, Jesús Urman, Javier Fernández, Mónica González, Miguel Navasa, Alberto Monescillo, Agustín Albillos, Wladimiro Jiménez, Vicente Arroyo
Journal: Hepatology (2003)

Spontaneous bacterial peritonitis (SBP) is frequently associated with renal failure. This study assessed if systemic and hepatic hemodynamics are also affected by this condition. Standard laboratory tests, tumor necrosis factor alpha (TNF-alpha) in plasma and ascitic fluid, plasma renin activity (PRA) and norepinephrine (NE), and systemic and hepatic hemodynamics were determined in 23 patients with SBP at diagnosis and after resolution of infection. Eight patients developed renal failure during treatment. At diagnosis of infection, patients developing renal failure showed significantly higher values of TNF-alpha, blood urea nitrogen (BUN), PRA and NE, peripheral vascular resistance, and hepatic venous pressure gradient (HVPG) and lower cardiac output than patients not developing renal failure. During treatment, a significant reduction in cardiac output and arterial pressure and increase in PRA and NE, HVPG, and Child-Pugh score were observed in the first group but not in the second. Peripheral vascular resistance remained unmodified in both groups. Changes in PRA and NE correlated inversely with changes in arterial pressure and directly with changes in BUN, Child-Pugh score, and HVPG. Five patients in the renal failure group developed encephalopathy, and 6 died. In the group without renal failure, none of the patients developed encephalopathy or expired. In conclusion, patients with SBP frequently develop a rapidly progressive impairment in systemic hemodynamics, leading to severe renal and hepatic failure, aggravation of portal hypertension, encephalopathy, and death. This occurs despite rapid resolution of infection and is associated with an extremely poor prognosis.
[Ca <sup>2+</sup> ] <sub>i</sub> Inhibition of K <sup>+</sup> Channels in Canine Renal Artery
Authors: Craig H. Gelband, Joseph R. Hume
Journal: Circulation Research (1995)

Abstract The patch-clamp technique was used to examine the inhibition of delayed rectifier K + channels by agents that release intracellular Ca 2+ . During voltage-clamp experiments on isolated myocytes with 4-aminopyridine (4-AP, 10 mmol/L) and niflumic acid (100 μmol/L) present to inhibit delayed rectifier K + current (I K(dr) ) and Ca 2+ -activated Cl − current (I Cl(Ca) ), angiotensin II (Ang II) and caffeine increased Ca 2+ -activated K + current (I K(Ca) ) between −25 and 80 mV (n=5). Conversely, with charybdotoxin (ChTX, 100 nmol/L) and niflumic acid (100 μmol/L) present to inhibit I K(Ca) and I Cl(Ca) , Ang II and caffeine only caused inhibition of I K(dr) . Block was achieved within 15 seconds of drug application and was reversible upon washout (n=5). The effects of Ang II on I K(Ca) and I K(dr) were inhibited by the specific Ang II receptor antagonist losartan (1 mmol/L, n=3). Intracellular BAPTA (10 mmol/L) also abolished the effects of Ang II and caffeine on both I K(Ca) and I K(dr) . In current-clamp experiments, the application of ChTX (100 nmol/L) and niflumic acid (100 μmol/L) caused little change in resting membrane potential; however, subsequent application of caffeine (10 mmol/L) caused a 26±2.9 mV depolarization from −54±3.1 to −28±1.7 mV (n=6). 4-AP (10 mmol/L) blocked the caffeine-induced depolarization. When isolated cells were loaded with the Ca 2+ indicator indo 1 (100 μmol/L), Ang II, caffeine, and 4-AP increased [Ca 2+ ] i and depolarized the cells. Both Ang II and caffeine caused an increase in [Ca 2+ ] i that preceded membrane depolarization, whereas 4-AP depolarized the cell first and then caused an increase in [Ca 2+ ] i (n=4). In inside-out patches, with 200 nmol/L ChTX in the patch pipette to block large-conductance Ca 2+ -activated K + channels, a 45±7-picosiemen 4-AP–sensitive K + channel was identified that was sensitive to cytoplasmic Ca 2+ (n=6). Increasing intracellular Ca 2+ decreased channel opening probability [N×P(open), where N is the number of functional channels in a patch and P(open) is the opening probability] at all membrane potentials examined. At 0 mV, increasing Ca 2+ from &lt;5 to 200 and 600 nmol/L free Ca 2+ decreased N×P(open) by 52±3% and 73±7%, respectively (n=6). The decrease in opening probability of the delayed rectifier K + channel resulted from a concentration- and voltage-dependent decrease in mean open time. The decrease in mean open time reflected significant decreases and increases in open and closed time constants, respectively. These results suggest that agonist-induced changes in intracellular Ca 2+ can alter vascular smooth muscle membrane potential through regulation of delayed rectifier K + channels.
Untreatable tuberculosis: is surgery the answer?
Authors: Masoud Dara, Giovanni Sotgiu, Richard Zaleskis, Giovanni Battista Migliori
Journal: European Respiratory Journal (2015)

According to the 2014 World Health Organization (WHO) Global Report, tuberculosis (TB) continues to be the most important infectious disease in terms of incidence and mortality, along with HIV/AIDS: 9 million new cases and 1.5 million deaths are estimated to have occurred in 2013 [1]. No TB elimination is possible till the prevalence of drug-resistant TB is lowered at the global level <http://ow.ly/GgUNg> The authors would like to thank Linda Barkane (Latvian Center for TB and Pulmonary Disease), who kindly provided the chest radiographs of the MDR-TB patients.
Hypothyroidism in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib
Authors: Brian I. Rini, Ila Tamaskar, Phillip Shaheen, Renee Salas, Jorge Garcia, Laura Wood, Sethu Reddy, Robert Dreicer, Ronald M. Bukowski
Journal: JNCI Journal of the National Cancer Institute (2007)

Sunitinib is an inhibitor of the vascular endothelial growth factor and platelet-derived growth factor receptors, and it has antitumor activity in metastatic renal cell carcinoma and gastrointestinal stromal tumors. To further investigate the fatigue associated with sunitinib therapy, thyroid function tests were performed on patients with metastatic renal cell carcinoma who were receiving sunitinib. Seventy-three patients with metastatic renal cell carcinoma were treated with sunitinib at the Cleveland Clinic Taussig Cancer Center, and 66 of them had thyroid function test results available. Fifty-six (85%) of the 66 patients had one or more abnormality in their thyroid function test results, consistent with hypothyroidism, and 47 (84%) of the 56 patients with abnormal thyroid function tests had signs and/or symptoms possibly related to hypothyroidism. Thyroid hormone replacement was undertaken in 17 patients, and symptoms improved in nine of them. Thyroid function test abnormalities appear to be common in patients with metastatic renal cell carcinoma treated with sunitinib, and routine monitoring is warranted.
Xanthine oxidoreductase activity in perfused hearts of various species, including humans.
Authors: J W de Jong, P van der Meer, A S Nieukoop, T Huizer, R J Stroeve, E Bos
Journal: Circulation Research (1990)

Oxygen free radicals generated by xanthine oxidase have been implicated in cardiac damage. The activity of xanthine oxidase/reductase in adult rat heart is considerable. Its assay gives controversial results for other species, for example, rabbits and humans. Therefore, we perfused isolated hearts of various species, including explanted human hearts, to measure the conversion of exogenous hypoxanthine to xanthine and urate. We assayed these purines with high-performance liquid chromatography. The apparent xanthine oxidoreductase activities, calculated as release of xanthine plus 2x urate, were (milliunits per gram wet weight, mean +/- SEM) mice 33 +/- 3 (n = 5), rats 28.5 +/- 1.4 (n = 9), guinea pigs 14.4 +/- 1.0 (n = 5), rabbits 0.59 +/- 0.09 (n = 5), pigs less than 0.1 (n = 6), humans 0.31 +/- 0.04 (n = 7), and cows 3.7 +/- 0.8 (n = 4). In rabbit heart the conversion of hypoxanthine to xanthine was slow, and that of xanthine to urate was even slower. On the other hand, guinea pig and human heart released little xanthine, indicating that xanthine breakdown exceeds its formation. We conclude that isolated perfused mouse, rat, guinea pig, and also bovine hearts show considerable xanthine oxidoreductase activity, contrasting rabbit, porcine, and diseased human hearts.