tbuckley/cabot-search huggingface dataset:
Heparan sulfate proteoglycan expression in normal human liver
Authors: Tania Roskams, Han Moshage, Rita de Vos, David Guido, Paul Yap, Valeer Desmet
Journal: Hepatology (1995)

Because increasing evidence implicates heparan sulfate proteoglycans (HSPGs) as essential cofactors in receptor-growth factor interactions, in cell-cell recognition systems, and in cell-matrix adhesion processes and yet little is known about their cellular distribution pattern and cellular sources in liver tissue, we used monoclonal antibodies specific for the core proteins of syndecan1, 2, 3, 4, glypican, and perlecan to investigate their immunohistochemical expression in normal adult human liver biopsy specimens. Syndecan1 was expressed in sinusoidal endothelial cells, whereas the endothelium of the portal tract vessels was negative. Hepatocytes showed a membranous staining pattern of the sinusoidal and intercellular domain. Bile duct epithelial cells showed basolateral membrane positivity. Immunoreactivity for syndecan2 was seen in mesenchymal cells, accentuated around bile ducts. Syndecan3 showed intense staining of hepatic arterial and portal venous endothelial cells, of mesenchymal cells, and of Ito cells. Immunohistochemistry for syndecan4 showed a granular staining pattern of hepatocytes at their bile canalicular pole. Glypican showed weak positivity in portal tract mesenchymal cells and clear positivity in nerve bundles. Perlecan was present in Disse's space, in endothelial cells, in basement membranes surrounding bile ducts and vessels, in vessel walls, and in mesenchymal cells. The highly differential expression of these HSPGs in the different cell compartments of the liver, as well as in basement membranes and in Disse's space, suggests that each of these proteoglycans has a specific function in the interplay of cells, matrix molecules, growth factors, and proteinases.
Surgery of the Biliary Tract
Authors: T Taylor
Journal: BMJ (1994)

Ed James Toouli Churchill Livingstone, £69.50, pp 457 ISBN 0-443-04361-2

Biliary surgery is evolving rapidly in the light of technological advances in investigation, diagnosis, and surgical techniques. Surgery of the Biliary Tract is a readable, well illustrated, and comprehensive text on the subject, which makes useful reading for general surgeons. It is written by a truly international selection of experts from all corners of the globe, including Australia, Europe, the United States, …
New Carbon Dioxide-Independent Basal Growth Medium for Culture of Diverse Tumor and Nontumor Cells of Human and Nonhuman Origin
Authors: David T. Vistica, Dominic Scudiero, Philip Skehan, Anne Monks, Michael R. Boyd
Journal: JNCI Journal of the National Cancer Institute (1990)

A eukaryotic growth medium (Program Development Research Group Basal Growth Medium) was developed for CO2-independent maintenance and propagation of human and nonhuman tumor cell lines representing diverse histologies (e.g., cancers of the brain, colon, lung, ovary, and kidney, as well as leukemia and melanoma). It was also shown to be suitable for the maintenance and propagation of nontumor cells of human and nonhuman derivation. The medium derives its buffering capacity primarily from beta-glycerophosphate, exhibits a stable physiologic pH of 7.3-7.4, and is optimized to facilitate growth in atmospheric CO2. It is also useful in cellular growth and cytotoxicity assays based on either the metabolic reduction of tetrazolium reagents or protein staining. The 50% inhibitory concentration values obtained with carmustine, doxorubicin, and tamoxifen in cell lines maintained in the new medium under atmospheric CO2 were closely comparable to those obtained with these drugs against cells maintained in RPMI-1640 under a 5% CO2 environment.
Predominant role of gluconeogenesis in the hepatic glycogen repletion of diabetic rats.
Authors: A Giaccari, L Rossetti
Journal: Journal of Clinical Investigation (1992)

Liver glycogen formation can occur via the direct (glucose----glucose-6-phosphate----glycogen) or indirect (glucose----C3 compounds----glucose-6-phosphate----glycogen) pathways. In the present study we have examined the effect of hyperglycemia on the pathways of hepatic glycogenesis, estimated from liver uridine diphosphoglucose (UDPglucose) specific activities, and on peripheral (muscle) glucose metabolism in awake, unstressed control and 90% pancreatectomized, diabetic rats. Under identical conditions of hyperinsulinemia (approximately 550 microU/ml), 2-h euglycemic (6 mM) and hyperglycemic (+5.5 mM and +11 mM) clamp studies were performed in combination with [3-3H,U-14C]glucose, [6-3H,U-14C]glucose, or [3-3H]glucose and [U-14C]lactate infusions under postabsorptive conditions. Total body glucose uptake and muscle glycogen synthesis were decreased in diabetic vs. control rats during all the clamp studies, whereas glycolytic rates were similar. By contrast, hyperglycemia determined similar rates of liver glycogen synthesis in both groups. Nevertheless, in diabetic rats, the contribution of the direct pathway to hepatic glycogen repletion was severely decreased, whereas the indirect pathway was markedly increased. After hyperglycemia, hepatic glucose-6-phosphate concentrations were increased in both groups, whereas UDPglucose concentrations were reduced only in the control group. These results indicate that in the diabetic state, under hyperinsulinemic conditions, hyperglycemia normally stimulates liver glycogen synthesis through a marked increase in the indirect pathway, which in turn may compensate for the reduction in the direct pathway. The increase in the hepatic concentrations of both glucose-6-phosphate and UDPglucose suggests the presence, in this diabetic rat model, of a compensatory "push" mechanism for liver glycogen repletion.
First-Line Trastuzumab Plus Epirubicin and Cyclophosphamide Therapy in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Cardiac Safety and Efficacy Data From the Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) Trial
Authors: Michael Untch, Michael Muscholl, Sergei Tjulandin, Walter Jonat, Hans-Gerd Meerpohl, Mikhail Lichinitser, Alexey G. Manikhas, Alexandra Coumbos, Rolf Kreienberg, Andreas du Bois, Nadia Harbeck, Christian Jackisch, Volkmar Müller, Matthias Pauschinger, Christoph Thomssen, Michaela Lehle, Olivier Catalani, Hans-Joachim Lück
Journal: Journal of Clinical Oncology (2010)

A high incidence of congestive heart failure (CHF) has been observed in patients with metastatic breast cancer (MBC) receiving doxorubicin-based chemotherapy and trastuzumab. The Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) trial evaluated trastuzumab plus cyclophosphamide and the less cardiotoxic anthracycline epirubicin.This prospective trial combined a phase I dose-finding stage with a phase II randomized stage. In total, 120 patients with human epidermal growth factor receptor 2 (HER2) -positive MBC and adequate cardiac function received first-line trastuzumab (4 mg/kg intravenous loading dose, then 2 mg/kg every week) plus cyclophosphamide (600 mg/m(2)) and either epirubicin 60 mg/m(2) (HEC-60) or 90 mg/m(2) (HEC-90) for six cycles, followed by trastuzumab monotherapy until progression. Sixty patients with HER2-negative disease received epirubicin (90 mg/m(2)) and cyclophosphamide (EC-90) alone. The primary end point was dose-limiting cardiotoxicity (DLC).Incidence of DLC was 5.0%, 1.7%, and 0% in the HEC-90, HEC-60, and EC-90 arms, respectively. All DLC events were manageable. There were no cardiac-related deaths. Other adverse-event profiles were comparable across the three arms, except febrile neutropenia, which was reported in 10% of the HEC-90 arm compared with 3% of the other arms. Tumor response rates were 57%, 60%, and 25% in the HEC-60, HEC-90, and EC-90 arms, respectively; median time to progression was 12.5, 10.1, and 7.6 months, respectively.The HEC regimen is a promising treatment option for patients with HER2-positive MBC. The lower incidence of DLC with HEC, compared with the historic incidence associated with trastuzumab plus doxorubicin, supports further evaluation of the regimen, especially in adjuvant or neoadjuvant settings.
Prognostic Value of Tumoral Thymidylate Synthase and p53 in Metastatic Colorectal Cancer Patients Receiving Fluorouracil-Based Chemotherapy: Phenotypic and Genotypic Analyses
Authors: Marie-Christine Etienne, Maurice Chazal, Pierre Laurent-Puig, Nicolas Magné, Christophe Rosty, Jean-Louis Formento, Mireille Francoual, Patricia Formento, Nicole Renée, Emmanuel Chamorey, André Bourgeon, Jean-François Seitz, Jean-Robert Delpero, Christian Letoublon, Denis Pezet, Gérard Milano
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The aim of this multicenter prospective study was to evaluate the role of intratumoral parameters related to fluorouracil (FU) sensitivity in 103 metastatic colorectal cancer patients receiving FU–folinic acid. PATIENTS AND METHODS: Liver metastatic biopsy specimens were obtained for all patients and primary tumor biopsy specimens for 54 patients. Thymidylate synthase (TS), folylpolyglutamate synthetase, and dihydropyrimidine dehydrogenase were measured by radioenzymatic assays; TS promoter polymorphism (2R/2R v 2R/3R v 3R/3R) was determined by polymerase chain reaction; and p53 protein and mutations were analyzed by immunoluminometric assay and denaturing gradient gel electrophoresis, respectively. RESULTS: p53 mutations were observed in 56.7% of metastases. TS activity was significantly higher in 2R/3R tumors as compared with 2R/2R or 3R/3R. TS activity in metastasis was the only parameter linked to clinical responsiveness (responders exhibited the lower TS, P = .047). Univariate Cox analyses demonstrated that TS activity in primary tumor (the greater the TS, the poorer the survival; P = .040), TS promoter polymorphism in primary tumor (risk of death of 2R/3R v 2R/2R, 2.68; P = .035), and p53 stop mutation in metastasis (risk of death of stop mutations v wild type, 3.14; P = .018) were the only significant biologic predictors of specific survival. Stepwise analysis did not discriminate between TS activity and TS polymorphism. CONCLUSION: Present results confirm the value of tumoral TS activity for predicting FU responsiveness, point out the importance of detailed p53 mutation analysis for predicting survival, and suggest that TS genotype in primary tumor carries a prognostic value similar to that of TS activity.
Bleeding in renal failure: is von Willebrand factor implicated?
Authors: G Remuzzi, M Livio, M C Roncaglioni, G Mecca, M B Donati, G de Gaetano
Journal: BMJ (1977)

Normal or increased concentrations of factor VIII procoagulant activity (VIIIC), factor VIII-related antigen (VIIIRA), and factor VIII-von Willebrand activity (VIIIVWF) were found in the predialysis plasma of 10 out of 11 patients with chronic renal failure (CRF). All patients had a bleeding time longer than 15 minutes and platelet retention to glass beads lower than 40%. The only patient who had reduced concentrations of all three factor VIII complex components was subsequently shown to have von Willebrand9s disease. In four patients with CRF, very low platelet retention, and slightly prolonged bleeding time none of the three factor VIII COMPLEX COMPONENTS WERE SELECTIVely modified in predialysis samples. These findings suggest that the bleeding tendency common in CRF is not necessarily linked to defective plasma factor VIII-related activities.
Transglutaminase is essential for IgA nephropathy development acting through IgA receptors
Authors: Laureline Berthelot, Christina Papista, Thiago T. Maciel, Martine Biarnes-Pelicot, Emilie Tissandie, Pamela H.M. Wang, Houda Tamouza, Agnès Jamin, Julie Bex-Coudrat, Aurelie Gestin, Ahmed Boumediene, Michelle Arcos-Fajardo, Patrick England, Evangéline Pillebout, Francine Walker, Eric Daugas, François Vrtosvnik, Martin Flamant, Marc Benhamou, Michel Cogné, Ivan C. Moura, Renato C. Monteiro
Journal: The Journal of Experimental Medicine (2012)

IgA nephropathy (IgAN) is a common cause of renal failure worldwide. Treatment is limited because of a complex pathogenesis, including unknown factors favoring IgA1 deposition in the glomerular mesangium. IgA receptor abnormalities are implicated, including circulating IgA–soluble CD89 (sCD89) complexes and overexpression of the mesangial IgA1 receptor, TfR1 (transferrin receptor 1). Herein, we show that although mice expressing both human IgA1 and CD89 displayed circulating and mesangial deposits of IgA1–sCD89 complexes resulting in kidney inflammation, hematuria, and proteinuria, mice expressing IgA1 only displayed endocapillary IgA1 deposition but neither mesangial injury nor kidney dysfunction. sCD89 injection into IgA1-expressing mouse recipients induced mesangial IgA1 deposits. sCD89 was also detected in patient and mouse mesangium. IgA1 deposition involved a direct binding of sCD89 to mesangial TfR1 resulting in TfR1 up-regulation. sCD89–TfR1 interaction induced mesangial surface expression of TGase2 (transglutaminase 2), which in turn up-regulated TfR1 expression. In the absence of TGase2, IgA1–sCD89 deposits were dramatically impaired. These data reveal a cooperation between IgA1, sCD89, TfR1, and TGase2 on mesangial cells needed for disease development. They demonstrate that TGase2 is responsible for a pathogenic amplification loop facilitating IgA1–sCD89 deposition and mesangial cell activation, thus identifying TGase2 as a target for therapeutic intervention in this disease.
A Nested Case-Control Study of Plasma 25-Hydroxyvitamin D Concentrations and Risk of Colorectal Cancer
Authors: K. Wu, D. Feskanich, C. S. Fuchs, W. C. Willett, B. W. Hollis, E. L. Giovannucci
Journal: JNCI Journal of the National Cancer Institute (2007)

Low vitamin D status has long been implicated in colorectal carcinogenesis. We investigated this relationship in a nested case–control study within the Health Professionals Follow-up Study (HPFS), a large ongoing study of male health professionals living in the United States. Between 1993 and 2002, 179 colorectal cancer patients were diagnosed and matched to 356 control subjects by age and by month and year of blood collection. Results were also pooled with previously published results from the Nurses’ Health Study (NHS) cohort, a large female cohort. Conditional logistic regression was used to analyze the association between plasma 25-hydroxyvitamin D [25(OH)D] and colorectal cancer, and pooled estimates were calculated using the method of DerSimonian and Laird. All statistical tests were two-sided. In the HPFS, we observed a non–statistically significant inverse association between higher plasma 25(OH)D concentration and risk of colorectal cancer and a statistically significant inverse association for colon cancer (highest versus lowest quintile: odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.24 to 0.89; Ptrend = .005). After pooling the results from the HPFS and NHS, higher plasma 25(OH)D concentrations were statistically significantly associated with decreased risks of both colorectal cancer (highest versus lowest quintile, OR = 0.66, 95% CI = 0.42 to 1.05; Ptrend = .01) and colon cancer (highest versus lowest quintile, OR = 0.54, 95% CI = 0.34 to 0.86; Ptrend = .002). Inverse associations with plasma 25(OH)D concentration did not differ by location of colon cancer (proximal versus distal), but the number of patients was small and none of the associations was statistically significant. Opposite relationships between plasma 25(OH)D levels and risk of rectal cancers were found among men (positive) and women (inverse). Our data provide additional support for the inverse association between vitamin D and colorectal and, in particular, colon cancer risk.
Intraarticular methylprednisolone therapy in hemophilic arthropathy
Authors: R. Shupak, J. Teitel, M. B. Garvey, J. Freedman
Journal: American Journal of Hematology (1988)

Abstract This small pilot study examined the use of intraarticular methylprednisolone in hemophilic synovitis. Nineteen joints in ten adult hemophiliacs were studied. There was subjective improvement at 24 hr following injection in 79% of joints injected, and the improvement persisted up to 8 wk in 58%. The number of hemarthroses decreased following intraarticular steroids (mean of 7.7 bleeds in the 8 wk prior to injection versus a mean of 1.9 bleeds in the 8 wk following injection). Similarly the amount of clotting factor used for the injected target joint decreased from a mean of 7,616 units to 2,315 units postinjection (p &lt;.001). Improvement correlated with presence of synovitis but not with radiologic stage of the joint. Aspirated synovial fluids were analyzed and showed characteristics consistent with low‐grade inflammation. These preliminary observations suggest that intraarticular corticosteroid injection may be a useful therapeutic tool in the medical management of hemophilic arthropathy.
Expression of metallothionein-I and II in skin ageing and its association with skin proliferation
Authors: C. Ma, L.-F. Li, X. Chen
Journal: British Journal of Dermatology (2010)

Background Metallothioneins (MT) are important antioxidants involved in the ageing process of many tissues and organs. To our knowledge, the role of MT in skin ageing has not been reported. Objectives To investigate the expression of MT in ageing skin. Methods The protein levels of MT-I and MT-II in sun-exposed and sun-protected skin specimens obtained from healthy individuals were detected by immunohistochemistry using tissue microarray and expressed as average integrated optical density (AIOD). Proliferating cell nuclear antigen (PCNA) and Ki-67 protein levels in these specimens were also detected to study the possible link between the proliferation of keratinocytes and expression of MT. Results The protein levels of MT-I and MT-II decreased significantly with increasing age of sun-exposed and sun-protected skin (r = −0·73 and −0·98, respectively, P < 0·01) but was more prominent in sun-exposed skin. In sex- and age-matched specimens, the intensity of MT-I and MT-II in sun-exposed skin was much lower than in sun-protected skin (9·46 ± 2·39 vs. 22·25 ± 8·04, mean ± SD of AIOD, P < 0·01, Student’s t-test). The expression of PCNA and Ki-67 showed the same trend. Conclusions The expression of MT-I and MT-II declined with the decrease of keratinocyte proliferation in the process of skin ageing, and this decline was more significant in sun-exposed skin. Whether MT-I and MT-II supplementation could inhibit skin ageing, especially photoageing, merits further study.
The role of gender on clearance of hepatitis C virus: a different story in an area endemic for hepatitis B and C
Authors: C.-Y. Dai, J.-F. Huang, M.-Y. Hsieh, L.-P. Lee, C.-K. Ho, W.-L. Chuang, M.-L. Yu
Journal: Gut (2007)

setting that provides close observation for 1 hour after a biopsy.However, we keep a conservative and different view on the sufficiency and safety of 1 hour observation time after a liver biopsy.We have performed a total of 3806 liver biopsies using 18-gauge needle on 2980 patients (males 1817, females 1163, mean age was 41.3 years, range 17-72 years), performed in a medical centre and in a core regional hospital in southern Taiwan from Jan 1996 through Sep 2006.Our outpatient biopsy was assigned to a 6-hour observation time.The reasons for the liver biopsy studies on these patients, were either a result of chronic viral hepatitis or a surveillance of abnormal liver function tests.There was no clinical evidence of cirrhosis diagnosed by high-resolution ultrasound before a biopsy.Patients who have thrombocytopenia or the presence of oesophageal varices, ascites, splenomegaly, signs of portal hypertension, or encephalopathy by other imaging studies as well as bleeding tendencies, were excluded.These procedures have been done by six well-trained, board certified hepatologists.Apart from minor complications such as pain, nausea, and vomiting, a total of 12 patients (0.32%) suffered from haemorrhagic complications 4 to 12 hours after the biopsy (table 1).Our results were comparable with those of Beddy et al in terms of major complications and mortality.Although there was no death at follow up of one week, four patients did experienced hypovolemic shock.In one patient, haemobilia, presenting with insidious onset of tarry stool, obstructive jaundice, and hypovolemic shock, developed 24 hours after the biopsy.The total in-hospital days therefore were extended and ranged from 1 to 7 days.In rare occasions haemorrhagic complications such as haemoperitoneum, haemothorax, and haemobilia did occur with potential risk of morbidity and mortality after the procedure.Noteworthy is that those with poor performance such as liver cirrhosis and bleeding tendency were excluded from our study.Major complications occurred in four patients after the regular observation time.This does, indicate a possible need of a longer time of observation.Therefore, our study with a 6-hour observation time basis concluded that although ultrasound-guided liver biopsy is generally a safe procedure, major haemorrhage complications may occur more than one hour after liver biopsy.A longer time of observation may be more suitable with this potential risky procedure.
Aplastic Carcinoma in Diabetic Mice: Hyperglycemia-Suppressed Proliferation Rate and Insulin Synthesis by Tumor Cells
Authors: K Pavelić
Journal: JNCI Journal of the National Cancer Institute (1979)

Increased glucose levels in blood of diabetic and of normoinsulinemic hyperglycemic CBA/H mice were accompanied by suppressed growth of aplastic carcinoma. Tumors maintained in diabetic mice grew faster after each subsequent transplantation into diabetic mice, but those maintained in hyperglycemic normoinsulinemic mice grew at a constant rate. Evidence revealed that tumor growth was suppressed by hyperglycemia. The observed proliferation enhancement of aplastic carcinoma maintained in diabetic mice was caused by de novo insulin synthesis, probably by the tumor cells themselves.