tbuckley/cabot-search huggingface dataset:
Clinical value of gallium-67 scintigraphy in assessment of disease activity in Wegener's granulomatosis
Authors: R H J A Slart
Journal: Annals of the Rheumatic Diseases (2003)

Diagnosis of active pulmonary and paranasal involvement in patients with Wegener's granulomatosis (WG) can be difficult. The diagnostic value of gallium-67 scintigraphy in WG is unclear.To evaluate the added diagnostic value of gallium-67 scintigraphy in patients with WG with suspected granulomatous inflammation in the paranasal and chest regions.Retrospectively, the diagnostic contribution of chest and head planar gallium scans in 40 episodes of suspected vasculitis disease activity in 28 patients with WG was evaluated. Scans were grouped into normal or increased uptake for each region. Histological proof or response to treatment was the "gold standard" for the presence of WG activity.WG activity was confirmed in 8 (20%) episodes, with pulmonary locations in three, paranasal in four, and both in one (n=7 patients); all these gallium scans showed increased gallium uptake (sensitivity 100%). Gallium scans were negative for the pulmonary area in 23/36 scans (specificity 64%), and negative for paranasal activity in 13/16 scans (specificity 81%) in episodes without WG activity. Positive predictive value of WG activity for lungs and paranasal region was 24% and 63%, respectively, negative predictive value was 100% for both regions. False positive findings were caused by bacterial or viral infections.Gallium scans are clinically helpful as a negative scan virtually excludes active WG. Gallium scintigraphy of chest and nasal region has a high sensitivity for the detection of disease activity in WG. However, because of positive scans in cases of bacterial or viral infections, specificity was lower.
Abdominal pain in a patient with an oesophageal stent
Authors: K T Tan
Journal: Gut (2005)

Background and aims: When saliva, with its high nitrite content derived from the enterosalivary recirculation of dietary nitrate, meets acidic gastric juice, the nitrite is converted to nitrous acid, nitrosative species, and nitric oxide.In healthy volunteers this potentially mutagenic chemistry is focused at the gastric cardia.We have studied the location of this luminal chemistry in Barrett's patients during acid reflux.Methods: Ten Barrett's patients were studied before and after administration of 2 mmol nitrate.Using microdialysis probes we measured nitrite, ascorbic acid, total vitamin C, and thiocyanate concentrations and pH simultaneously in the proximal oesophagus, Barrett's segment, hiatal sac, proximal stomach, and distal stomach.In a subgroup, real time nitric oxide concentrations were also measured.Results: During acid reflux, Barrett's segment was the anatomical site with maximal potential for acid catalysed nitrosation, with its median concentration of nitrite exceeding that of ascorbic acid in two of 10 subjects before nitrate and in four of nine after nitrate.Thiocyanate, which catalyses acid nitrosation, was abundant at all anatomical sites.On entering the acidic Barrett's segment, there was a substantial fall in nitrite and the lowest ascorbic acid to total vitamin C ratio, indicative of reduction of salivary nitrite to nitric oxide at this anatomical site.Episodes of acid reflux were observed to generate nitric oxide concentrations of up to 60 mM within the Barrett's segment. Conclusion:The interaction between acidic gastric refluxate and nitrite rich saliva activates potentially mutagenic luminal nitrosative chemistry within Barrett's oesophagus.
Inactivation of fatty acid synthase impairs hepatocarcinogenesis driven by AKT in mice and humans
Authors: Lei Li, Giulia M. Pilo, Xiaolei Li, Antonio Cigliano, Gavinella Latte, Li Che, Christy Joseph, Marta Mela, Chunmei Wang, Lijie Jiang, Silvia Ribback, Maria M. Simile, Rosa M. Pascale, Frank Dombrowski, Matthias Evert, Clay F. Semenkovich, Xin Chen, Diego F. Calvisi
Journal: Journal of Hepatology (2015)
DNA Repair Gene Polymorphisms and Risk of Pancreatic Cancer
Authors: Donghui Li, Hideo Suzuki, Bingrong Liu, Jeffrey Morris, Jun Liu, Taro Okazaki, Yanan Li, Ping Chang, James L. Abbruzzese
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The current research was undertaken to examine the association between genetic variations in DNA repair and pancreatic cancer risk. Experimental Design: We analyzed 9 single nucleotide polymorphisms of 7 DNA repair genes (LIG3, LIG4, OGG1, ATM, POLB, RAD54L, and RECQL) in 734 patients with pancreatic adenocarcinoma and 780 healthy controls using the Taqman method. Information on cigarette smoking, alcohol consumption, medical history, and other risk factors was collected by personal interview. Results: The homozygous mutant genotype of LIG3 G-39A [odds ratio (OR), 0.23; 95% confidence interval (CI), 0.06-0.82; P = 0.027] and ATM D1853N (OR, 2.55; 95% CI, 1.08-6.00; P = 0.032) was significantly associated with altered risk for pancreatic cancer. A statistically significant interaction of ATM D1853N and LIG4 C54T genotype with diabetes on the risk of pancreatic cancer was also detected. Compared with nondiabetics with the ATM D1853N GG genotype, nondiabetics with the GA/AA, diabetics with the GG, and diabetics with the GA/AA genotypes, respectively, had ORs (95% CI) of 0.96 (0.74-1.24), 1.32 (0.89-1.95), and 3.23 (1.47-7.12; Pinteraction = 0.032, likelihood ratio test). The OR (95% CI) was 0.91 (0.71-1.17), 1.11 (0.73-1.69), and 2.44 (1.34-4.46) for nondiabetics carrying the LIG4 CT/TT genotype, diabetics with the CC genotype, and diabetics carrying the CT/TT genotype, respectively, compared with nondiabetics carrying the CC genotype (Pinteraction = 0.02). Conclusions: These observations suggest that genetic variations in DNA repair may act alone or in concert with other risk factors on modifying a patient's risk for pancreatic cancer.
Excretion of pyridinium crosslinks correlates with disease activity and appendicular bone loss in early rheumatoid arthritis.
Authors: A K Gough, N F Peel, R Eastell, R L Holder, J Lilley, P Emery
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVE--To establish if urinary excretion rates of the collagen crosslinks pyridinoline and deoxypyridinoline, which are known to be elevated in established rheumatoid arthritis (RA), are useful markers of bone loss in this disease. METHODS--Eight hour urine collections on all patients and 52 controls were performed, and the rates of pyridinoline and deoxypyridinoline excretion were measured. Bone mineral density (BMD), by dual energy x-ray absorption, and full laboratory and clinical assessments were performed. RESULTS--The rates of excretion of pyridinoline and deoxypyridinoline were significantly increased in patients compared with controls (p &lt; 0.001). Pyridinoline excretion was associated with increased disease activity (ESR/CRP) but not disability (HAQ score/Functional Grade), and correlated with BMD loss at the femoral neck (p &lt; 0.01). CONCLUSION--The excretion of collagen crosslinks may be useful as markers of bone and cartilage turnover in patients with RA.
Hepatic ito cells contain calcium channels: Increases with transforming growth factor-β 1
Authors: Hirosumi Oide, Ronald G. Thurman
Journal: Hepatology (1994)

Ito cells (fat–storing cells) have been implicated in mechanisms of liver fibrosis, and transforming growth factor–β1 is a key factor that stimulates collagen production by Ito cells. Moreover, Ito cells are reported to possess contractile proteins and to contract with ligands. We recently reported the presence of L–type voltage–operated Ca2+ channels in Kupffer cells. In this study, we examined whether Ito cells contain Ca2+ channels and also evaluated the effect of transforming growth factor–β1 on Ca2+ channels. Cytosolic free calcium concentration was measured in individual cultured Ito cells with the fluorescent Ca2+ indicator dye fura–2. Partial replacement of extracellular Na+ with K+ caused an increase in cytosolic free calcium, presumably as a result of transmembrane Ca2+ influx. Basal cytosolic free calcium levels were around 40 to 50 nmol/L in both control and transforming growth factor–β1—treated cells. In transforming growth factor–β1—treated cells, cytosolic free calcium increased in response to K+ at values as low as 10 mmol/L, whereas untreated cells did not respond. Half–maximal increases in cytosolic free calcium in transforming growth factor–β1—treated cells were observed with 63 ± 6 mmol/L K+. With 100 mmol/L K+, intracellular free calcium increased around fourfold above basal values in transforming growth factor–β1—treated cells but was only increased about twofold in untreated controls. We conclude that this increase in cytosolic free calcium occurs by way of voltage–operated calcium channels; it did not occur in the absence of extracellular calcium and cannot be explained by Na+/Ca2+ exchange mechanisms. The influx of Ca2+ was only about one third as large on subsequent depolarizations and was not sensitive to the dihydropyridine–type calcium channel agonist BAY K 8644. In contrast, Ca2+ influx was inhibited by the dihydropyridine–type calcium channel blocker nitrendipine. These data indicate that Ito cells contain voltage–operated Ca2+ channels. Furthermore, transforming growth factor–β1 activates or up–regulates these Ca2+ channels.(HEPATOLOGY 1994;20:1009–1014)
Androgen Mediation of Thrombocytosis in Epithelial Ovarian Cancer Biology
Authors: Andrew John Li, Beth Young Karlan
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Preoperative thrombocytosis (platelet count &amp;gt; 400 × 109/L) at initial exploration for epithelial ovarian carcinoma is associated with decreased surgical cytoreducibility and poor survival. Platelets express androgen receptor (AR), which contains a polymorphic CAG trinucleotide repeat sequence of which the length inversely correlates with AR transactivation function. We hypothesized that androgen-mediated thrombocytosis promotes aggressive ovarian cancer biology. Experimental Design: Sixty-three patients with epithelial ovarian carcinoma underwent genotype analysis of the CAG repeat polymorphism in AR. Medical records were reviewed to assess preoperative thrombocytosis, surgical findings, and survival. Data were examined using the Fisher's exact, logistic regression, and Kaplan-Meier analyses. Results: AR CAG repeat lengths ranged from 8 to 27, with a median of 23. Fifteen of 63 patients (23.8%) showed preoperative thrombocytosis. Short AR allelotype (≤ 20 CAG repeats) was associated with a higher incidence of thrombocytosis (P = 0.04). The combination of short AR allelotype and thrombocytosis was the only significant factor that predicted inability to achieve optimal surgical cytoreduction (P = 0.02). Women with short AR allelotype and thrombocytosis showed statistically decreased progression-free survival (13 versus 37 months, P = 0.01) and overall survival (37 versus 65 months, P = 0.02) when compared with women with long AR allelotype and normal platelet counts. On multivariate analyses, suboptimal cytoreduction was the only significant factor predictive of disease-specific overall survival (P = 0.0002) but the combination of short AR allelotype and thrombocytosis approached statistical significance (P = 0.08). Conclusions: Androgen modulation of thrombocytosis may promote aggressive epithelial ovarian cancer biology.
Photodynamic therapy inhibits p-glycoprotein mediated multidrug resistance via JNK activation in human hepatocellular carcinoma using the photosensitizer pheophorbide a
Authors: Patrick Ming-Kuen Tang, Dong-Mei Zhang, Ngoc-Ha Bui Xuan, Stephen Kwok-Wing Tsui, Mary Miu-Yee Waye, Siu-Kai Kong, Wing-Ping Fong, Kwok-Pui Fung
Journal: Molecular Cancer (2009)

Abstract Background Multidrug resistance (MDR) is frequently observed after prolonged treatment in human hepatoma with conventional anti-tumor drugs, and photodynamic therapy (PDT) is a recently suggested alternative to overcome MDR. The therapeutic potential of PDT was evaluated in a multidrug resistance (MDR) human hepatoma cell line R-HepG2 with photosensitizer pheophorbide a (Pa). Results Our results demonstrated that intracellular accumulation of Pa was not reduced by the overexpression of P-glycoprotein. Pa-based PDT (Pa-PDT) significantly inhibited the growth of R-HepG2 cells with an IC50 value of 0.6 μM. Mechanistic study demonstrated that genomic DNA fragmentation and phosphatidylserine externalization occurred where increase of intracellular singlet oxygen level triggers the phosphorylation of c-Jun N-terminal Kinase (JNK) and leads to activation of intrinsic apoptotic caspases cascade during the Pa-PDT treatment. The cytotoxicity of Pa-PDT, accumulation of sub-G1 population, and depolarization of mitochondrial membrane could be inhibited by JNK inhibitor in the Pa-PDT treated cells. Interestingly, the Pa-PDT induced JNK activation showed inhibitory effect on MDR by the down-regulation of P-glycoprotein in R-HepG2 cells in a dose-dependent manner. In addition, significant reduction of tumor size was obtained in Pa-PDT treated R-HepG2-bearing nude mice with no significant damages in liver and heart. Conclusion In summary, our findings provided the first evidence that PDT could inhibit the MDR activity by down-regulating the expression of P-glycoprotein via JNK activation using pheophorbide a as the photosensitizer, and our work proved that Pa-PDT inhibited the growth of MDR hepatoma cells by mitochondrial-mediated apoptosis induction.
Serum uric acid is associated with mortality and heart failure hospitalizations in patients with complicated myocardial infarction: findings from the High-Risk Myocardial Infarction Database Initiative
Authors: Thomas G. von Lueder, Nicolas Girerd, Dan Atar, Stefan Agewall, Zohra Lamiral, Mehmet Kanbay, Bertram Pitt, Kenneth Dickstein, Faiez Zannad, Patrick Rossignol
Journal: European Journal of Heart Failure (2015)
Lymph and pulmonary response to isobaric reduction in plasma oncotic pressure in baboons.
Authors: C K Zarins, C L Rice, R M Peters, R W Virgilio
Journal: Circulation Research (1978)

Plasma colloid osmotic pressure was reduced by 76% (from 19.6 +/- 0.6 to 4.7 +/- 1.5 mm Hg) in five baboons while pulmonary capillary hydrostatic pressure was maintained at a normal level. This resulted in fluid retention, weight gain, peripheral edema and ascites, but no pulmonary edema. Thoracic duct lymph flow increased 6-fold and pulmonary lymph flow 7-fold. Thoracic duct lymph had a lower colloid osmotic pressure (2.0 +/- 0.7 mm Hg) than plasma (4.7 +/- 1.5 mm Hg), whereas the colloid osmotic pressure of pulmonary lymph (4.7 +/- 0.7 mm Hg) was the same as that of plasma. The lymph-plasma ratio for albumin fell in thoracic duct lymph but remained unchanged in pulmonary lymph. The difference between plasma colloid osmotic pressure and pulmonary artery wedge pressure decreased from 15.3 +/- 1.9 to -0.7 +/- 2.9 mm Hg. Despite this increase in filtration force, the lungs were protected from edema formation by a decrease of 11 mm Hg in pulmonary interstitial colloid osmotic pressure and a 7-fold increase in lymph flow.
Actions of the 5-hydroxytryptamine 1 receptor agonist sumatriptan on interdigestive gastrointestinal motility in man
Authors: J Tack, B Coulie, A Wilmer, T Peeters, J Janssens
Journal: Gut (1998)

Pharmacological studies of the enteric nervous system have shown the presence of several subtypes of 5-hydroxytryptamine (5HT) receptor, which might be involved in control of the migrating motor complex.To study the effect of sumatriptan, an agonist of enteric neuronal 5HT1p receptors, on interdigestive motility in man.In 12 healthy subjects, interdigestive motility was recorded manometrically in the upper gastrointestinal tract. In seven subjects blood samples were drawn every 15 minutes for radioimmunoassay of motilin and somatostatin. After two phase 3s of the migrating motor complex, 6 mg of sumatriptan was administered subcutaneously. Recording continued until two more phase 3s had occurred.Sumatriptan induced a premature phase 3 in the jejunum after a median of 10 (8) minutes. The duration of the migrating motor complex cycle was shortened at the expense of phase 2. After sumatriptan, plasma somatostatin concentrations were reduced and gastric phase 3s were suppressed, although median motilin concentrations and the occurrence of plasma motilin peaks were not affected. Phase 3s of the migrating motor complex preceding sumatriptan were associated with motilin peaks, while phase 3s after sumatriptan were not. Furthermore, pretreatment with sumatriptan prevented the induction of a gastric phase 3 by the motilin agonist erythromycin.Administration of the 5HT1P receptor agonist sumatriptan induces a premature intestinal phase 3, suppresses gastric phase 3s, prevents induction of a gastric phase 3 by erythromycin, and reduces plasma somatostatin concentrations.
Efforts to create an artificial testis: culture systems of male germ cells under biochemical conditions resembling the seminiferous tubular biochemical environment
Authors: N. Sofikitis, E. Pappas, A. Kawatani, D. Baltogiannis, D. Loutradis, N. Kanakas, D. Giannakis, F. Dimitriadis, K. Tsoukanelis, I. Georgiou, G. Makrydimas, Y. Mio, V. Tarlatzis, M. Melekos, I. Miyagawa
Journal: Human Reproduction Update (2005)

Induction of meiotic and post-meiotic alterations of male germ cells in vitro has been the target of several research efforts since 1960. However, to date, the establishment of an ideal culture system in which spermatogonial stem cells can be maintained and directed to proliferate and undergo meiosis and complete spermiogenesis does not exist. This is attributed to the difficulties concerning the isolation and purification of defined subpopulations of germ cells and the establishment of male germ cell lines. In addition, there is no adequate knowledge regarding the optimal biochemical conditions that promote the survival and differentiation of germ cells in long-term cultures. This review focuses on the methodologies that have been proved sufficient to achieve differentiation of cultured male germ cells. Furthermore, the factors regulating spermatogenesis and the technical prerequisites to achieve differentiation of cultured male germ cells are described. Finally, the role of in vitro cultures of immature diploid germ cells in the therapeutic management of men negative for haploid cells in their testes and the subsequent potential genetic and epigenetic risks are discussed.
The effect of epidermal growth factor on brush border surface area and function in the distal remnant following resection in the rabbit
Authors: J A Hardin, B Chung, E V O’Loughlin, D G Gall
Journal: Gut (1999)

Background Epidermal growth factor (EGF) has been shown to increase intestinal absorptive surface area and transport function in normal animals. Aims To examine the effect of EGF on absorptive surface area and brush border membrane function in a model of massive small bowel resection. Methods New Zealand white rabbits were randomised into two groups: a resected group (60% proximal small bowel resection); and an unmanipulated control group. Distal remnant tissue was examined 10 and 21 days postsurgery. In separate experiments oral EGF (40 μg/kg/day) was administered to resected animals from days 3 to 8 and animals were studied on day 10. Results Ten days postsurgery brush border surface area and total absorptive surface area were significantly increased in remnant tissue while brush border membrane vesicle (BBMV) glucose uptake was significantly decreased compared with controls. By 21 days brush border surface area returned to control levels though BBMV glucose uptake remained depressed. EGF treatment induced a further increase in brush border surface area in remnant intestine but did not alter BBMV glucose uptake. Conclusions Surgical resection results in significant elevations in absorptive surface area coupled with a decrease in brush border membrane transport function distal to the site of anastomosis. EGF enhances glucose uptake in remnant intestine via recruitment of additional microvillus membrane into the brush border.
Still a long way to go to achieve multidisciplinarity for the benefit of patients: commentary on the ESMO position paper (Annals of Oncology 25(1): 9–15, 2014)
Authors: V. Valentini, P.-A. Abrahamsson, S.K. Aranda, A. Astier, R.A. Audisio, M. Boniol, L. Bonomo, A. Brunelli, B. Bultz, A. Chiti, F. De Lorenzo, J.G. Eriksen, V. Goh, M.K. Gospodarowicz, L. Grassi, J. Kelly, R.D. Kortmann, T. Kutluk, A. Plate, G. Poston, T. Saarto, R. Soffietti, A. Torresin, W.H. van Harten, J.F. Verzijlbergen, C. von Kalle, P. Poortmans
Journal: Annals of Oncology (2014)
Long term effects of radiation of T and B lymphocytes in peripheral blood of patients with Hodgkin's disease.
Authors: Z Fuks, S Strober, A M Bobrove, T Sasazuki, A McMichael, H S Kaplan
Journal: Journal of Clinical Investigation (1976)

Total lymphocyte counts, and the percentage of T and B lymphocytes and monocytes in untreated patients with Hodgkin's disease were not significantly different from those observed in normal donors. At the completion of radiotherapy, the mean total lymphocyte count of 503/mm3 was 4 SD below the mean for normal controls. Although a group of 26 patients in continuous complete remission from 12 to 111 mo after radiation treatment regained normal total numbers of lymphocytes and monocytes, they exhibited a striking T lymphocytopenia and B lymphocytosis. Concomitantly, there was a significant increase of null (neither T nor B) lymphocytes. The response of peripheral blood lymphocytes to phytohemagglutinin, concanavalin A, and tetanus toxoid before treatment was significantly impaired. 1-10 yr after completion of treatment there seemed to be little or no recovery of these responses. The capacity of peripheral blood lymphocytes to respond to allo-antigens on foreign lymphocytes in vitro (mixed lymphocyte reaction) was normal in nine untreated patients. However, the mixed lymphocyte reaction was markedly impaired during the first 2 yr after treatment. There was a partial and progressive restoration of the mixed lymphocyte reaction during the next 3 yr, and normal responses were observed in patients in continuous complete remission for 5 yr or more. The in vivo response to dinitrochlorobenzene was also examined. 88% (15/17) of patients initially sensitive to dinitrochlorobenzene were anergic to the allergen at the completion of a course of radiotherapy, but nine of these regained their hypersensitivity response during the 1st yr after treatment. This data suggests that there is a sustained alteration in both the number and function of circulating T cells after radiation therapy in patients with Hodgkin's disease which may persist for as long as 10 yr after treatment. The restoration of cell mediated immune functions after radiotherapy is time dependent and its kinetics may differ for various T-cell functions. The implications of these findings with respect to the state of immunological competence after radiotherapy are discussed.