tbuckley/cabot-search huggingface dataset:
Changes in WNT/β-catenin pathway during regulated growth in rat liver regeneration
Authors: Satdarshan P.S. Monga, Peter Pediaditakis, Karen Mule, Donna Beer Stolz, George K. Michalopoulos
Journal: Hepatology (2001)

The wnt/β–catenin pathway is important during embryogenesis and carcinogenesis. β–Catenin interaction with E–cadherin has been shown to be crucial in cell–cell adhesion. We report novel findings in the wnt pathway during rat liver regeneration after 70% partial hepatectomy using Western blot analyses, immunoprecipitation studies, and immunofluorescence. We found wnt–1 and β–catenin proteins to be predominantly localized in hepatocytes. Immediately following partial hepatectomy, we observed an initial increase in β–catenin protein during the first 5 minutes with its translocation to the nucleus. We show this increase to be the result of decreased degradation of β–catenin (decrease in serine phosphorylated β–catenin) as seen by immunoprecipitation studies. We observed activation of β–catenin degradation complex comprising of adenomatous polyposis coli gene product (APC) and serine–phosphorylated axin protein, beginning at 5 minutes after hepatectomy, leading to its decreased levels after this time. Quantitative changes observed in E–cadherin protein during liver regeneration are, in general, reverse to those seen in β–catenin. In addition, using immunoprecipitation, we observe elevated levels of tyrosine–phosphorylated β–catenin at 6 hours onward. Thus, changes in the wnt pathway during regulated growth seem to tightly regulate cytosolic β–catenin levels and may be contributing to induce cell proliferation and target gene expression. Furthermore, these changes might also be intended to negatively regulate cell–cell adhesion for structural reorganization during the process of liver regeneration.
THE VALUE OF TRIAMCINOLONE AND VITAMIN A IN THE TREATMENT OF PSORIASIS..
Authors: A. JARRETT, R. I. SPEARMAN
Journal: British Journal of Dermatology (1959)

Journal Article THE VALUE OF TRIAMCINOLONE AND VITAMIN A IN THE TREATMENT OF PSORIASIS.: Preliminary Communication. Get access A. JARRETT, A. JARRETT Department of Dermatology, University College Hospital Medical School, Landon, W.C.I Search for other works by this author on: Oxford Academic Google Scholar R. I. SPEARMAN R. I. SPEARMAN Department of Dermatology, University College Hospital Medical School, Landon, W.C.I Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 71, Issue 7, 1 July 1959, Pages 267–269, https://doi.org/10.1111/j.1365-2133.1959.tb13423.x Published: 01 July 1959
Biogenic Amines and Affective Disorders
Authors: J J Schildkraut
Journal: Annual Review of Medicine (1974)

In recent years the study of biogenic amine metabolism in patients with affective disorders (depressions and manias) has been stimulated by the increasing evidence that drugs used in the treatment of these disorders produce changes in the metabo­ lism of one of the monoamines (i.e. the catecholamines, norepinephrine, and dopa­ mine, as well as the indoleamine serotonin) (1). These studies, which have demonstrated a number of different biochemical alterations in patients with affective disorders, have contributed substantially to our understanding of the underlying pathophysiology of these disorders. Aspects of this literature have been reviewed frequently during the past several years (1-16). For a number of years investigators have recognized the possibility that different subtypes of depressive or manic disorders might exhibit different specific alterations in the metabolism of the monoamines. It was suggested that studies of biogenic amine metabolism might ultimately contribute to the development of a more mean­ ingful biochemical classification of the affective disorders and a more rational ap­ proach to the treatment of these disorders (2, 17). Since I had the opportunity to prepare a fairly extensive review of this field for the Annual Review of Pharmacology last year (16), I do not repeat much of this material in the present review. Instead, I emphasize studies that have appeared during the past year, focusing principally on those areas of research that now appear most likely to yield biochemical criteria for classifying different types of affective disorders and predicting differential re­ sponses to various forms of treatment.
Human B lymphocyte subsets. I. IgG-bearing B cell response to pokeweed mitogen.
Authors: K A Ault, M Towle
Journal: The Journal of Experimental Medicine (1981)

The subset of B lymphocytes having IgG on their surfaces was purified from human spleen and blood using a fluorescence-activated cell sorter (FACS). This subset constituted about 15% of B lymphocytes. The remaining non-IgG-bearing B cells were also obtained for study. These two populations were examined for (a) their expression of other surface immunoglobulin isotypes, (b) their ability to give rise to IgG- and IgM-secreting (plaque-forming) cells in a pokeweed mitogen (PWM)-driven culture system, and (c) their ability to proliferate in response to PWM stimulation. The results of these studies indicate that most IgG-bearing B cells also express surface IgM and IgD. Less than 15% had only IgG. The IgG-positive cell gave rise to both IgG and IgM plaque-forming cells when driven by PWM, and in fact were responsible for most of the total plaque response in both the IgG and IgM classes. The non-IgG-bearing B cells were depleted of both IgG and IgM responsiveness. The failure of the non-IgG-bearing B cells to give a strong response to PWM did not appear to be due to either depletion of accessory cells or to any suppressive influence. Finally, proliferation studies indicated that both the IgG-bearing and the non-IgG-bearing cells proliferated in the presence of PWM with a somewhat stronger proliferative response in the IgG-bearing cells. These results demonstrate that the IgG-bearing cell is not irreversibly committed to IgG production but can also give rise to IgM-secreting cells, and that human PWM-driven immunoglobulin secretory responses are predominantly due to a numerically small subset of B cells.
Right Lymphatic Duct Distribution Volume in Dogs
Authors: EDWARD C. MEYER, ROSEMARIE OTTAVIANO
Journal: Circulation Research (1974)

Steady-state ratios of the concentration in lymph to that in plasma were measured for 125 I-serum albumin after 4 days of equilibration in unanesthetized dogs. Subsequently, acute experiments 3-8 hours in duration were carried out in the same dogs under anesthesia to measure the exchange kinetics of 131 I-serum albumin in right duct lymph and thoracic duct lymph. The albumin distribution volume in the field of right lymphatic duct drainage was calculated and compared with the pulmonary interstitial fluid volume measured using 14 C-sucrose. For the right lymphatic duct, a single rate constant ( K R ) was sufficient to account for equilibration up to 3-8 hours. The mean value of K R was 2.35 x 10 -3 ± 0.99 x 10 -3 min -1 (half-time 5.6 ± 1.96 hours). In contrast, equilibration of thoracic duct lymph was multiexponential over this period. The concentration of 125 I-albumin in lung interstitial water was 74% of that in corresponding right duct lymph. At 3-8 hours (termination of the acute experiment), fractional equilibration of interstitial albumin calculated from 131 I-albumin wash-in kinetics was 0.33 ± 0.1 and that of right duct lymph was 0.34 ± 0.11, indicating that the K R measured for the latter reflects the equilibration process in lung interstitial fluid. The mean distribution volume drained by the right lymphatic duct was 0.92 ± 0.42 ml/kg. Subtracting the reported cardiac lymph distribution volume and correcting the remainder for albumin concentration relative to lymph suggests that about 28% of the lung lymph drains into the right lymphatic duct.
Association between Chronic Kidney Disease and Coronary Artery Calcification
Authors: Holly Kramer, Robert Toto, Ronald Peshock, Richard Cooper, Ronald Victor
Journal: Journal of the American Society of Nephrology (2004)

The hypothesis that chronic kidney disease (CKD) is associated with increased coronary artery calcification (CAC) was tested using data from the Dallas Heart Study, a representative sample of Dallas County residents aged 30 to 65 yr. CKD was defined as presence of microalbuminuria and GFR ≥60 ml/min per 1.73 m2 (stage 1 to 2), or GFR <60 ml/min per 1.73 m2 (stage 3 to 5), excluding end-stage kidney disease. Logistic regression was used to examine the association between stages of CKD and CAC scores >10, >100, and >400 versus scores ≤10 compared with no CKD while adjusting for covariates. Analyses were repeated after stratifying by presence of diabetes. The mean age was 43.9 yr, and hypertension and diabetes were noted in 31.0 and 9.8%, respectively. No association was noted between stage 1 to 2 CKD and increased CAC scores. Compared with no CKD, stage 3 to 5 CKD was associated with CAC scores >100 (odds ratio, 2.85; 95% confidence interval, 0.92 to 8.80) and >400 (odds ratio, 8.35; 95% confidence interval, 1.94 to 35.95) in the total population after adjustment for covariates, but these associations were substantially reduced after exclusion of participants with diabetes. Participants with diabetes and stage 3 to 5 CKD had a ninefold increased odds of CAC scores >10 versus scores ≤10 compared with participants with diabetes and without CKD, whereas no association was noted between stage 3 to 5 CKD and CAC scores >10 in the nondiabetic population. In conclusion, stage 3 to 5 CKD is associated with increased CAC scores, but this association may be substantially stronger among adults with diabetes. These findings need to be confirmed in study populations that include adults >65 yr of age and a larger number of CKD cases.
Polycystic ovarian disease: heritability and heterogeneity
Authors: P. G. Crosignani, A. E. Nicolosi
Journal: Human Reproduction Update (2001)

The polycystic appearance of the ovary is the distinguishing characteristic of polycystic ovary syndrome (PCOS) but there is a wide range of other clinical and biochemical features, e.g. elevated serum concentrations of androgens, insulin, LH and decreased insulin sensitivity. The high prevalence of affected individuals and the wide range of related phenotypes can be explained by the interaction of a small number of key genes with environmental factors. Heritability of PCOS has been inferred from studies of the syndrome in various populations (ethnic groups, twins and PCOS families). The data suggest that the condition is passed down through either sex, according to an autosomal dominant model of genetic transmission. To date, specific gene mutations affecting androgen synthesis, insulin secretion and insulin activity explain most of the endocrine and metabolic symptoms, while environmental risk factors (either during prenatal or post-natal life), seem to convert an occult PCOS into a clinically manifest syndrome.
In-Facility Delirium Prevention Programs as a Patient Safety Strategy
Authors: James T. Reston, Karen M. Schoelles
Journal: Annals of Internal Medicine (2013)

Delirium, an acute decline in attention and cognition, occurs among hospitalized patients at rates estimated to range from 14% to 56% and increases the risk for morbidity and mortality. The purpose of this systematic review was to evaluate the effectiveness and safety of in-facility multicomponent delirium prevention programs. A search of 6 databases (including MEDLINE, EMBASE, and CINAHL) was conducted through September 2012. Randomized, controlled trials; controlled clinical trials; interrupted time series; and controlled before–after studies with a prospective postintervention portion were eligible for inclusion. The evidence from 19 studies that met the inclusion criteria suggests that most multicomponent interventions are effective in preventing onset of delirium in at-risk patients in a hospital setting. Evidence was insufficient to determine the benefit of such programs in other care settings. Future comparative effectiveness studies with standardized protocols are needed to identify which components in multicomponent interventions are most effective for delirium prevention.
The XY female in sport: the controversy continues.
Authors: L J Hipkin
Journal: British Journal of Sports Medicine (1993)

The summer and winter Olympic Games have been accompanied by much press coverage of the controversy and confusion over sex tests for sportswomen. Much of this has centred on the eligibility of subjects with androgen insensitivity to compete in women's events. The purpose of this paper is to review the process of sex differentiation and its abnormalities, highlighting those conditions in which biologically active testosterone is secreted which might confer an advantage in women's sporting events.
EVI1 promotes tumor growth via transcriptional repression of MS4A3
Authors: Gerwin Heller, Anna Rommer, Katarina Steinleitner, Julia Etzler, Hubert Hackl, Petra Heffeter, Erwin Tomasich, Martin Filipits, Birgit Steinmetz, Thais Topakian, Simone Klingenbrunner, Barbara Ziegler, Andreas Spittler, Sabine Zöchbauer-Müller, Walter Berger, Rotraud Wieser
Journal: Journal of Hematology & Oncology (2015)

The transcription factor Ecotropic Virus Integration site 1 (EVI1) regulates cellular proliferation, differentiation, and apoptosis, and its overexpression contributes to an aggressive course of disease in myeloid leukemias and other malignancies. Notwithstanding, knowledge about the target genes mediating its biological and pathological functions remains limited. We therefore aimed to identify and characterize novel EVI1 target genes in human myeloid cells. U937T_EVI1, a human myeloid cell line expressing EVI1 in a tetracycline regulable manner, was subjected to gene expression profiling. qRT-PCR was used to confirm the regulation of membrane-spanning-4-domains subfamily-A member-3 (MS4A3) by EVI1. Reporter constructs containing various parts of the MS4A3 upstream region were employed in luciferase assays, and binding of EVI1 to the MS4A3 promoter was investigated by chromatin immunoprecipitation. U937 derivative cell lines experimentally expressing EVI1 and/or MS4A3 were generated by retroviral transduction, and tested for their tumorigenicity by subcutaneous injection into severe combined immunodeficient mice. Gene expression microarray analysis identified 27 unique genes that were up-regulated, and 29 unique genes that were down-regulated, in response to EVI1 induction in the human myeloid cell line U937T. The most strongly repressed gene was MS4A3, and its down-regulation by EVI1 was confirmed by qRT-PCR in additional, independent experimental model systems. MS4A3 mRNA levels were also negatively correlated with those of EVI1 in several published AML data sets. Reporter gene assays and chromatin immunoprecipitation showed that EVI1 regulated MS4A3 via direct binding to a promoter proximal region. Experimental re-expression of MS4A3 in an EVI1 overexpressing cell line counteracted the tumor promoting effect of EVI1 in a murine xenograft model by increasing the rate of apoptosis. Our data reveal MS4A3 as a novel direct target of EVI1 in human myeloid cells, and show that its repression plays a role in EVI1 mediated tumor aggressiveness.
Dental and facial injuries in international field hockey.
Authors: J H Bolhuis, J M Leurs, G E Flögel
Journal: British Journal of Sports Medicine (1987)

In many respects international sportsmen are trendsetters for the behaviour of recreational sportsmen. For this reason the attitude of international hockey players towards mouth protectors was studied. The possession and use of mouth protectors vary markedly between different countries. The incidence of dental-facial traumas among international field hockey players is high; 54% had sustained injuries necessitating a visit to a physician and/or a dentist. Of these victims 20% sustained serious dental damage at least once (women 16% and men 22%). Only 20% of the international players wear a mouth protector consistently during training and matches. Women use the apparatus almost twice as much as men. The main argument in rejecting a mouth protector is that it is not felt to be necessary.
Protollin Adjuvanted Birch Pollen Extract Induces Long-Term Prevention of Airway Inflammation in a Mouse Model of Allergic Asthma
Authors: C.R. Rioux, N. Karp, H. Koohsari, A. Migneault, D.S. Burt, J.G. Martin, Q.A. Hamid
Journal: Journal of Allergy and Clinical Immunology (2006)
Feedback, group-level processes, and systems approaches in human evolution
Authors: Agustin Fuentes
Journal: Behavioral and Brain Sciences (2014)

An explicit role for emergent group-level traits, social role diversification, and coordination makes good sense when thinking about human evolution. To most effectively understand these and other facets, we need to move toward an integrative model that assumes niche construction and encompasses positive feedback systems at individual, subgroup and larger group levels, demographic processes, and local ecologies.
Evaluation of methotrexate and corticosteroids for the treatment of localized scleroderma (morphoea) in children
Authors: L. Weibel, M.C. Sampaio, M.T. Visentin, K.J. Howell, P. Woo, J.I. Harper
Journal: British Journal of Dermatology (2006)

Background Localized scleroderma (LS) or morphoea is often considered to be a benign self-limiting condition confined to the skin and subcutaneous tissue. However, the course of the disease is unpredictable and severe functional and cosmetic disability may result. Drug treatment with systemic corticosteroids in combination with methotrexate has been reported to be beneficial in LS, but data in children is limited. Objectives To evaluate the efficacy and tolerability of systemic corticosteroids in combination with methotrexate in children with LS. Methods Treatment and outcome of 34 patients with LS were retrospectively analysed. Pulsed intravenous methylprednisolone was given, followed by oral prednisolone on a reducing regimen and maintenance treatment with methotrexate. We assessed treatment outcome clinically and by thermography and monitored adverse events. Results From the onset of treatment, the disease stopped progressing in 94% of the patients. All patients demonstrated significant clinical improvement within a mean time of 5·7 ± 3·9 months. Mean duration of follow-up over the treatment period and beyond was 2·9 ± 2·0 years. In 16 (47%) patients therapy was discontinued when the disease was considered to be inactive clinically; however, seven (44%) of the 16 developed a relapse, necessitating repeat treatment. At last follow-up (range 0·2–7·0 years), 24 (71%) of the 34 patients had completely inactive disease. Observed adverse events were moderate and transient and no patient had to stop therapy. Conclusions These data suggest that systemic corticosteroids and methotrexate in combination are beneficial and well tolerated in the treatment of children with LS. Because of the risk of relapse after discontinuing therapy, long-term monitoring is mandatory.
Budd-Chiari syndrome and veno-occlusive disease/sinusoidal obstruction syndrome
Authors: D-C Valla
Journal: Gut (2008)

The hepatic venous system extends from the central veins of the hepatic lobule, up to the hepatic vein ostia into the inferior vena cava (IVC). There are numerous hepatic veins. The three major hepatic veins open into the IVC close to the right atrium. The hepatic venous system can be involved in arterio-venous or porto-venous fistulas, mostly of congenital origin, a topic which has been recently reviewed1 and will not be discussed here. Most of the other disorders of the hepatic venous system eventually cause its obstruction. Significant hepatic venous outflow block occurs either from a diffuse involvement in small vein diseases, or from a focal or extensive obstruction in diseases of the largest veins. So-called Budd–Chiari syndrome (BCS) is the liver disease resulting from the hepatic venous outflow block. The hepatic venous system can be invaded or compressed by malignant tumours of the liver, primary leimyosarcoma of the veins, or hepatic echinococcal disease. These diseases cause secondary BCS, which will not be discussed here. Primary BCS relates to the primary venous lesions including phlebitis, thrombosis or fibrosis.

Veno-occlusive disease (VOD) is characterised by particular, non-thrombotic, microvascular lesions without involvement of the large veins, occurring in a particular context of exposure to endothelial toxins. By convention, VOD has been separated from primary BCS, although VOD also causes hepatic outflow blockade, and mimics most clinical and laboratory features of primary BCS. Due to the particularities of VOD, and in order to make the distinction from BCS more clear, it was recently proposed to replace the denomination of VOD by sinusoidal obstruction syndrome (SOS).2

### Background

#### Epidemiology

Primary BCS is a rare disease. Accurate estimates of incidence are lacking for western countries. In Japan, in 1989, an incidence estimate derived from a questionnaire survey and an autopsy registry was 0.2 per million inhabitants …
Alteration of the Mitochondrial Apoptotic Pathway Is Key to Acquired Paclitaxel Resistance and Can Be Reversed by ABT-737
Authors: Ozgur Kutuk, Anthony Letai
Journal: Cancer Research (2008)

Abstract Paclitaxel is a microtubule-targeting antineoplastic drug widely used in human cancers. Even when tumors are initially responsive, progression of disease despite continued taxane therapy is all too common in the treatment of many of the most common epithelial cancers, including breast cancer. However, the mechanisms underlying paclitaxel resistance in cancer cells are not completely understood. Our hypothesis is that changes in the intrinsic (or mitochondrial) cell death pathway controlled by the BCL-2 family are key to the development of acquired paclitaxel resistance. Here we show that paclitaxel activates the mitochondrial apoptosis pathway, which can be blocked by BCL-2 overexpression. Treatment with ABT-737, a small-molecule BCL-2 antagonist, restores sensitivity to paclitaxel in BCL-2–overexpressing cells. To investigate the importance of changes in the intrinsic apoptotic pathway in the absence of enforced BCL-2 expression, we generated two independent breast cancer cell lines with acquired resistance to apoptosis induced by paclitaxel. In these lines, acquired resistance to paclitaxel is mediated either by increased antiapoptotic BCL-2 proteins or decreased proapoptotic BCL-2 proteins. In both cases, ABT-737 can engage the mitochondrial apoptosis pathway to restore sensitivity to paclitaxel to cell lines with acquired paclitaxel resistance. In summary, these findings suggest that alterations in the intrinsic apoptotic pathway controlled by BCL-2 protein family members may be crucial to causing paclitaxel resistance. Furthermore, our results suggest that combining small-molecule BCL-2 antagonists with paclitaxel may offer benefit to patients with paclitaxel-resistant tumors, an oncologic problem of great prevalence. [Cancer Res 2008;68(19):7985–94]