tbuckley/cabot-search huggingface dataset:
Alterations in tight junctions differ between primary biliary cirrhosis and primary sclerosing cholangitis
Authors: Shotaro Sakisaka, Takumi Kawaguchi, Eitaro Taniguchi, Shinichiro Hanada, Kurumi Sasatomi, Hironori Koga, Masaru Harada, Rina Kimura, Michio Sata, Norimasa Sawada, Michio Mori, Satoru Todo, Toshihiko Kurohiji
Journal: Hepatology (2001)

Tight junctions (TJ) of biliary epithelial cells (BEC) and hepatocytes prevent bile regurgitation from the biliary tract. Alterations in these TJs may participate in chronic cholestatic liver diseases such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). We examined the localization of 2 TJ proteins, ZO-1 and 7H6, in these diseases. Frozen sections from livers of PBC, PSC, extrahepatic cholestasis (Ex-C), and hepatitis C-associated cirrhosis (LC-C), as well as histologically normal livers, were processed for double-fluorescence immunohistochemistry. In controls and cirrhosis, 7H6 and ZO-1 colocalized surrounding the luminal space of the bile ducts and outlined the bile canalicular spaces between hepatocytes. In untreated PBC, immunostaining for ZO-1 in BEC of bile ducts 40 to 80 microm in diameter was preserved, but that for 7H6 was diminished to absent. In PBC treated with ursodeoxycholic acid (UDCA), immunostaining for 7H6 was well preserved. In PSC as well as in Ex-C, immunostaining for both 7H6 and ZO-1 was well preserved in bile ducts. In hepatocytes, ZO-1 showed preserved immunoreactivity, but immunostaining for 7H6 frequently disappeared. The percentage of bile ducts with immunostaining for 7H6 in all bile ducts with immunostaining for ZO-1 was significantly reduced in PBC compared with that in control, LC-C, Ex-C, and PSC (all P <.0001). Substantial alteration in the TJ protein occurs predominantly in bile ducts in PBC and in hepatocytes in PSC, suggesting increased paracellular permeability along different paracellular routes for bile regurgitation in these chronic cholestatic liver diseases.
A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin-Johnson syndrome
Authors: C C Paulusma, M Kool, P J Bosma, G L Scheffer, F ter Borg, R J Scheper, G N Tytgat, P Borst, F Baas, R O Elferink
Journal: Hepatology (1997)

The human Dubin-Johnson syndrome (DJS) is a rare autosomal recessive liver disorder characterized by chronic conjugated hyperbilirubinemia. Patients have impaired hepatobiliary transport of non-bile salt organic anions. A highly similar phenotype has been described for a mutant Wistar rat strain, the transport-deficient (TR-) rat, which is defective in the canalicular multispecific organic anion transporter (cmoat). This protein mediates adenosine triphosphate-dependent transport of a broad range of endogenous and xenobiotic compounds across the (apical) canalicular membrane of the hepatocyte. The complementary DNA (cDNA) encoding rat cmoat has recently been cloned, and the mutation underlying the defect in TR- rats has been identified. In the present study, we have isolated the human homologue of rat cmoat, human cMOAT, and analyzed the corresponding cDNA from fibroblasts of a DJS patient for mutations. Our results show that a mutation in this gene is the cause of DJS.
Systemic <scp>EBV</scp>‐positive lymphoproliferative disease of childhood
Authors: Sophie Portsmore, Subarna Chakravorty, Evelyn Oppong, Raida Ahmad, Barbara J. Bain
Journal: American Journal of Hematology (2015)

A 2 1 =2-year-old Caucasian girl presented critically ill with fever, shock, and a recent hematemesis.She had a generalized purpuric rash, bruising, and scattered petechiae.Her liver was palpable 4 cm below the right costal margin but there was no lymphadenopathy or palpable splenomegaly.Blood tests showed: white blood cell count 0.9 3 10 9 /l, neutrophils 0.4 3 10 9 /l, lymphocytes 0.7 3 10 9 /l, hemoglobin concentration 79 g/l, and platelet count 7 3 10 9 /l.Coagulation tests showed disseminated intravascular coagulation.Following resuscitation, bone marrow aspiration and trephine biopsy were performed.The bone marrow aspirate showed prominent hemophagocytosis (left and center).Normal hemopoietic cells were greatly reduced.There was an infiltrate of medium sized atypical lymphoid cells (center and right); these had a high nucleocytoplasmic ratio, slight to moderate chromatin condensation, and moderately basophilic cytoplasm, often extending into blebs.Flow cytometric immunophenotyping of the aspirate identified a small population of abnormal cytotoxic CD8-positive T cells, which showed complete loss of CD5 and CD7, co-expressed CD38, and showed partial expression of CD56.On trephine biopsy sections, the cells of the lymphoid infiltrate expressed CD2, CD3, CD8, HLA-DR, granzyme B, weak CD7, and EBER (Epstein-Barr virus-encoded RNA).They did not express CD4, CD5, CD56, CD57, ALK1, or terminal deoxynucleotidyl transferase.Molecular analysis showed a clonal T cell expansion on a polyclonal background.The titer of Epstein-Barr virus (EBV) on PCR of whole blood was subsequently found to be very high with 20,000,000 copies of the virus per ml.A diagnosis of systemic EBV-positive lymphoproliferative disease of childhood was made [1].This condition is more common in Asia than in European countries and North America but some cases in Caucasian patients have been described previously [2].Hemophagocytosis is a common feature.
Spontaneous factor VIII inhibitor occurring in association with chronic graft‐versus‐host disease
Authors: Christopher W. Seidler, Letha E. Mills, Mary E. D. Flowers, Keith M. Sullivan
Journal: American Journal of Hematology (1994)

Abstract The development of spontaneously acquired Factor VIII inhibitors is rare and may lead to serious hemorrhagic sequeiae. We report here the case of a patient who acquired a Factor VIII inhibitor two years after an allogeneic bone marrow transplant for CML. This occurred in association with a flare of chronic graft versus host dlsease (GVDH). He responded to corticosteroid therapy. A review of autoimmune phenomena associated with chronic GVDH and the treatment of Factor VIII Inhibitors is discussed. © 1994 Wiley‐Liss, Inc.
A robust prognostic signature for hormone-positive node-negative breast cancer
Authors: Obi L Griffith, François Pepin, Oana M Enache, Laura M Heiser, Eric A Collisson, Paul T Spellman, Joe W Gray
Journal: Genome Medicine (2013)

Systemic chemotherapy in the adjuvant setting can cure breast cancer in some patients that would otherwise recur with incurable, metastatic disease. However, since only a fraction of patients would have recurrence after surgery alone, the challenge is to stratify high-risk patients (who stand to benefit from systemic chemotherapy) from low-risk patients (who can safely be spared treatment related toxicities and costs). We focus here on risk stratification in node-negative, ER-positive, HER2-negative breast cancer. We use a large database of publicly available microarray datasets to build a random forests classifier and develop a robust multi-gene mRNA transcription-based predictor of relapse free survival at 10 years, which we call the Random Forests Relapse Score (RFRS). Performance was assessed by internal cross-validation, multiple independent data sets, and comparison to existing algorithms using receiver-operating characteristic and Kaplan-Meier survival analysis. Internal redundancy of features was determined using k-means clustering to define optimal signatures with smaller numbers of primary genes, each with multiple alternates. Internal OOB cross-validation for the initial (full-gene-set) model on training data reported an ROC AUC of 0.704, which was comparable to or better than those reported previously or obtained by applying existing methods to our dataset. Three risk groups with probability cutoffs for low, intermediate, and high-risk were defined. Survival analysis determined a highly significant difference in relapse rate between these risk groups. Validation of the models against independent test datasets showed highly similar results. Smaller 17-gene and 8-gene optimized models were also developed with minimal reduction in performance. Furthermore, the signature was shown to be almost equally effective on both hormone-treated and untreated patients. RFRS allows flexibility in both the number and identity of genes utilized from thousands to as few as 17 or eight genes, each with multiple alternatives. The RFRS reports a probability score strongly correlated with risk of relapse. This score could therefore be used to assign systemic chemotherapy specifically to those high-risk patients most likely to benefit from further treatment.
Rapid diagnosis of sputum negative miliary tuberculosis using the flexible fibreoptic bronchoscope.
Authors: W S Kwee
Journal: Thorax (1987)

Extrinsic allergic alveolitis caused by a cold water humidifier SIR-We read with interest the report by Dr AS Robertson and others (January 1987;42:32-7) of extrinsic allergic alveo- litis caused by a cold water humidifier.The causative agent among the humidifier sludge responsible for the extrinsic allergic alveolitis remained elusive.There is a possibility that the alveolitis was due to bird fancier's lung caused by inhalation of avian droppings.This was not specifically sought by bronchial provocation testing despite the authors' findings of precipitating antibodies to budgerigar and pigeon droppings in all three subjects.Although there was no known contact with birds in any of these subjects, we have recently observed a reactivation of bird fancier's lung in a previous fancier who initially appeared to have had no avian contact for several years.Detailed investigations showed that she had been exposed to pigeon droppings through a skylight in the roof of the building in which she worked.Therefore can the authors reassure us that there was absolutely no likelihood of contamination of the humidifier with avian protein?In addition, we feel that it would have been informative to perform bronchial challenge testing with avian protein since a positive response in the presence of precipitins would be highly suggestive that this was the offending antigen in the sludge.
Emerging Concepts of Mental Illness and Models of Treatment: The Psychological Point of View
Authors: GEORGE W. ALBEE
Journal: American Journal of Psychiatry (1969)

This author reviews the evidence for the "sickness" model of mental illness and finds it to be inconclusive. Psychiatry, he argues, in insisting on its prerogatives of primary patient responsibility and control of treatment facilities, bases its justification either on rare and uncertain genetic and metabolic conditions or on the common chronic organic conditions it characteristically neglects; the typical person in psychiatric treatment is suffering from neither. The alternative presented here is a social-developmental model, which would emphasize the nurturance of strength rather than the search for and excision of weakness.
Flow-related responses of intracellular inositol phosphate levels in cultured aortic endothelial cells.
Authors: A R Prasad, S A Logan, R M Nerem, C J Schwartz, E A Sprague
Journal: Circulation Research (1993)

In vitro and in vivo evidence indicates that hemodynamic wall shear stress evokes a diversity of biological responses in vascular endothelial cells, ranging from cell shape changes to alterations in low density lipoprotein receptor expression. The signal transduction mechanisms by which the level of fluid mechanical shear stress is recognized by the endothelial cell and translated into these diverse biological responses remain to be elucidated. The present study focuses on the association between the onset of elevated shear stress and activation of the phosphoinositide signal transduction pathway, as measured by the intracellular release of inositol phosphates, in cultured bovine aortic endothelial cells (BAECs). BAECs were seeded, grown to confluence on large polyester sheets, and preincubated with 0.3 microCi/ml [3H]inositol for 24 hours before insertion in parallel-plate flow chambers for exposure to high shear stress (HS) at 30 dynes/cm2 or low shear stress (LS) at < 0.5 dyne/cm2 for periods ranging from 15 seconds to 24 hours. The induction of HS was associated with an early, transient but significant increase (142%, HS/LS x 100%) in inositol trisphosphate (IP3) measured at 15 seconds of shear stress exposure followed by a major peak in IP3 (189%) observed at 5 minutes after HS onset. After these initial increases, IP3 levels returned to near resting levels within 30 minutes of continued HS exposure and then continued to decline to significantly lower (75%) levels relative to LS-treated cells within 4 hours and remained lower throughout the remainder of the 24-hour HS exposure. LS-treated cells exhibited no significant changes in inositol phosphate levels throughout the 24-hour exposure periods. Exposure of BAECs to shear stress of 60 dynes/cm2 resulted in an approximately fourfold increase in IP3 levels (396%) measured at 5 minutes, almost double the levels measured in cells exposed to 30 dynes/cm2 for 5 minutes. Pretreatment of BAECs for 30 minutes with 5 mM neomycin, an inhibitor of phosphoinositide metabolism, before HS exposure inhibited both the early increases in inositol phosphates and subsequent cell elongation and alignment observed in untreated BAECs simultaneously exposed to HS without inhibiting protein synthesis. These results indicate that the exposure of cultured BAECs to elevated wall shear stress is associated with an early biphasic IP3 increase followed by a resetting of intracellular inositol phosphate concentrations to levels below that observed in static cultured BAECs. Furthermore, neomycin inhibition of this IP3 response to shear stress is associated with an inhibition of one of the major endothelial biological responses to shear stress, i.e., cell shape change and orientation.(ABSTRACT TRUNCATED AT 400 WORDS)
Does long-term entecavir treatment really reduce hepatocellular carcinoma incidence in patients with hepatitis B virus infection?
Authors: Gin-Ho Lo
Journal: Hepatology (2013)

I read with interest the article by Hosaka et al.1 regarding long-term entecavir treatment in the reduction of hepatocellular carcinoma (HCC) incidence in patients with hepatitis B virus (HBV) infection. The article was a retrospective study using propensity matching based on the outcome of interest to avoid bias and concluded that long-term therapy with entecavir could reduce HCC incidence. However, some points still need further clarification. Although the study was well matched by propensity score, the proportion of patients with alcoholism was still significantly higher in the control group. The severity of cirrhosis was not shown. It has been demonstrated that heavy alcohol consumption increases the incidence of HCC in HBV-related cirrhosis.2 The proportion of patients with follow-up duration <1 year and incomplete sample or clinical data excluded from the study was disproportionately higher in the control group than the entecavir group. Based on the exclusion criteria, HBV patients with HCC or suspicion of HCC on enrollment were not excluded from the study. Thus, a few patients with HCC should be theoretically noted in the first year of follow-up. The diagnosis of HCC among various groups was not blinded. The duration of follow-up was significantly longer in the control group, although this had been adjusted. It appeared that very few cases developed HCC in the 1 to 2 years of follow-up. This revealed that the development of HCC was not evenly distributed in each year. All these factors may elicit significant bias between groups. It is certain that entecavir is beneficial for HBV patients to reverse fibrosis/cirrhosis3; however, the reduction of HCC incidence requires a meta-analysis with large sample size or long-term follow-up of controlled studies to be more convincing.4, 5 Gin-Ho Lo, M.D. Department of Medical Research Digestive Center E-DA Hospital Kaohsiung I-Shou University Taiwan
Serum TIMP-1 and Response to the Aromatase Inhibitor Letrozole Versus Tamoxifen in Metastatic Breast Cancer
Authors: Allan Lipton, Kim Leitzel, Hilary A. Chaudri-Ross, Dean B. Evans, Suhail M. Ali, Laurence Demers, Peter Hamer, Sheryl Brown-Shimer, Karen Pierce, Victor Gaur, Walter Carney
Journal: Journal of Clinical Oncology (2008)

To determine the effect of elevated serum TIMP-1 on the response of patients with metastatic breast cancer to an aromatase inhibitor versus tamoxifen.Five hundred twenty-two patients estrogen receptor-positive metastatic breast cancer were randomly assigned to receive first-line hormone therapy with letrozole or tamoxifen. Serum tissue inhibitor of metalloproteinases-1 (TIMP-1) levels were measured using an enzyme-linked immunosorbent assay.Pretreatment serum TIMP-1 was elevated in 120 (23%) of 522 patients. Patients with elevated serum TIMP-1 had a significantly reduced objective response rate (19.2% v 30.6%; odds ratio, 0.54; P = .01), duration of response (median, 15.5 v 26.2 months; P = .001), time to treatment progression (TTP; median, 4.5 v 9.2 months; HR, 1.78; P = .0001), time to treatment failure (median, 3.5 v 9.0 months; HR, 1.77; P = .0001), and overall survival (median, 20.3 v 35.8 months; HR, 1.77; P = .0001) compared with patients with normal pretreatment TIMP-1 levels. Letrozole was superior to tamoxifen in both the normal serum TIMP-1 group (median TTP, 11.8 v 8.6 months; P = .003) and in the elevated serum TIMP-1 group (median, 6.1 v 3.2 months; P = .03) In multivariate analysis, elevated serum TIMP-1 remained an independent predictor of both shorter TTP (HR, 1.46; P = .002) and survival (HR, 1.44; P = .002), as did serum HER-2. Combined analysis of both serum TIMP-1 and HER-2/neu conferred additional ability to predict significantly different clinical outcomes compared to using either biomarker alone.Patients with elevated pretreatment serum TIMP-1 had a significantly reduced response and survival. Serum TIMP-1 was an independent predictive and prognostic factor. Blockade of TIMP-1 and HER-2/neu activity may be beneficial in a subset of patients with breast cancer.
Identification of laminin binding proteins in cell membranes of a human colon adenocarcinoma cell line.
Authors: A Stallmach, D Schuppan, J Dax, C Hanski, E O Riecken
Journal: Gut (1990)

The invasion of malignant cells through the basement membrane is a critical step in local infiltration and metastasis. Adhesion and invasion of malignant cells may be modulated by their receptor mediated binding to the basement membrane glycoprotein laminin. We studied the specific adhesion of human colon adenocarcinoma derived HT 29 cells to laminin and its proteolytic fragments. The major cell adhesion domain of laminin was localised in the central part of the cross shaped molecule. Immunoblotting experiments on separated HT 29 cell membranes using specific antibodies or radiolabelled laminin fragments revealed two major laminin-binding cell surface components with Mr of 67,000 and 69,000 D similar to the putative laminin receptor described for other tissues. Using a nitrocellulose filter disk assay, the specific interaction between cell surface binding proteins and proteolytic fragments originating from the central core of the laminin molecule could be further corroborated. In contrast, interaction of HT 29 cell membranes with the pentapeptide YIGSR (tyr-ile-gly-ser-arg), a sequence domain of the B1-chain of the laminin molecule, thought to be responsible for cell adhesion, was significantly weaker.
Plastic insulin syringes
Authors: F D. Hart
Journal: BMJ (1988)

Plastic insulin syringes SIR,-Nine years ago Greenough et al pointed out how seldom diabetics became infected by injecting themselves daily with insulin using the same disposable syringe on several occasions, sometimes for several weeks, simply by covering the needle (attached to the syringe) with its cap and leaving the syringe in the refrigerator.'They found no evidence of infection even when the syringe was used for up to two months.In the correspondence that followed Oli, from Nigeria, reported that his diabetics, who could often not afford glass syringes, used their plastic syringes on average for a month, but as few had refrigerators he advised them to put syringe and needles in a clean covered container or pot in a hole in the ground, and since 1974, when he started the diabetic clinic, he had seen no infections.2In 1985 Bloom detailed the advantages of plastic over glass syringes for insulin injections,3 and two years later, after a long campaign by the British Diabetic Association, they became available on general
Mutant Epidermal Growth Factor Receptor (EGFRvIII) Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting
Authors: John C. Sok, Francesca M. Coppelli, Sufi M. Thomas, Miriam N. Lango, Sichuan Xi, Jennifer L. Hunt, Maria L. Freilino, Michael W. Graner, Carol J. Wikstrand, Darell D. Bigner, William E. Gooding, Frank B. Furnari, Jennifer R. Grandis
Journal: Clinical Cancer Research (2006)

Epidermal growth factor receptor (EGFR) is overexpressed in head and neck squamous cell carcinoma (HNSCC) where expression levels correlate with decreased survival. Therapies that block EGFR have shown limited efficacy in clinical trials and primarily when combined with standard therapy. The most common form of mutant EGFR (EGFRvIII) has been described in several cancers, chiefly glioblastoma. The present study was undertaken to determine the incidence of EGFRvIII expression in HNSCC and the biological consequences of EGFRvIII on tumor growth in response to EGFR targeting.Thirty-three HNSCC tumors were evaluated by immunostaining and reverse transcription-PCR for EGFRvIII expression. A representative HNSCC cell line was stably transfected with an EGFRvIII expression construct. EGFRvIII-expressing cells and vector-transfected controls were compared for growth rates in vitro and in vivo as well as chemotherapy-induced apoptosis and the consequences of EGFR inhibition using the chimeric monoclonal antibody C225/cetuximab/Erbitux.EGFRvIII expression was detected in 42% of HNSCC tumors where EGFRvIII was always found in conjunction with wild-type EGFR. HNSCC cells expressing EGFRvIII showed increased proliferation in vitro and increased tumor volumes in vivo compared with vector-transfected controls. Furthermore, EGFRvIII-transfected HNSCC cells showed decreased apoptosis in response to cisplatin and decreased growth inhibition following treatment with C225 compared with vector-transfected control cells.EGFRvIII is expressed in HNSCC where it contributes to enhanced growth and resistance to targeting wild-type EGFR. The antitumor efficacy of EGFR targeting strategies may be enhanced by the addition of EGFRvIII-specific blockade.