tbuckley/cabot-search huggingface dataset:
Collagenous colitis with mucosal tears on endoscopic insufflation: a unique presentation
Authors: M Cruz-Correa, F Milligan, F M Giardiello, T M Bayless, M Torbenson, J H Yardley, Frank W Jackson, F Wilson Jackson
Journal: Gut (2002)

<b>Background:</b> Tauroursodeoxycholate (TUDC) provides partial protection against taurolithocholate (TLC) induced cholestasis, possibly by inducing a signalling cascade activating protein kinase C (PKC). The potential protective effects of β muricholic acid (β-MC), another 7-β-hydroxylated bile salt, have not previously been studied in TLC cholestasis. <b>Aims:</b> To study the effect of β-MC on TLC induced cholestasis and also to investigate further the effects of agents affecting intracellular signalling, notably DBcAMP (a cell permeable cAMP analogue) and several protein kinase inhibitors. <b>Methods:</b> Functional studies were carried out analysing the proportion of hepatocyte couplets able to accumulate the fluorescent bile acid analogue cholyl-lysyl-fluorescein (CLF) into their sealed canalicular vacuole (cVA of CLF assay). <b>Results:</b> It was found that both β-MC and DBcAMP were as effective as TUDC in protecting against TLC induced cholestasis. The PKC inhibitors staurosporin and H7 but not the specific protein kinase A (PKA) inhibitor KT5720 abolished the protective effects of TUDC and β-MC. BAPTA/AM, a chelator of intracellular Ca<sup>2+</sup>, significantly decreased the protective effect of both bile salts, and that of DBcAMP. PKC and PKA inhibitors had no effect on protection with DBcAMP. <b>Conclusions:</b> β-MC was as effective as TUDC in protecting against TLC cholestasis. Mobilisation of Ca<sup>2+</sup> and activation of PKC, but not of PKA, are involved in the anticholestatic effect of the two 7-β-hydroxylated bile salts. The hepatoprotective effects of DBcAMP involved Ca<sup>2+</sup> mobilisation, but not PKC or PKA activation.
(8) Pemphigus foliaceus associated with S.L.E.
Authors: B. R. Allen, W. G. Reeves
Journal: British Journal of Dermatology (1978)

Journal Article (8) Pemphigus foliaceus associated with S.L.E. Get access B. R. Allen, B. R. Allen General Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar W. G. Reeves W. G. Reeves General Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 98, Issue s16, 1 July 1978, Pages 33–34, https://doi.org/10.1111/j.1365-2133.1978.tb13610.x Published: 01 July 1978
The Neostriatal Mosaic: Multiple Levels of Compartmental Organization in the Basal Ganglia
Authors: C R Gerfen
Journal: Annual Review of Neuroscience (1992)

effects behavior. Most notable among these effects are those related to the voluntary control of movement, which is compromised by neurodegenera­ tive diseases that involve the basal ganglia. Two such diseases, Parkinson's disease and Huntington's chorea, display a spectrum of movement impair­ ment (Albin et al 1989). Parkinson's disease, which results in the degener­ ation of dopaminergic systems in the basal ganglia, produces a disability to initiate desired movements. On the other hand, Huntington's chorea, which results in the degeneration of the major projection neurons of the basal ganglia, is characterized by uncontrolled movements. The complexity of these and other disorders that accompany basal ganglia dysfunction suggest its broad role in the subtlest components of voluntary movement. That memory, motivational, and emotional aspects of movement behavior are affected by this neural system is related to the fact that the striatum, which is the principal component of the basal ganglia, receives inputs from virtually all cortical areas (Carman et al 1965; Kemp & Powell 1970; Webster 1961), including limbic-related areas (Heimer & Wilson 1975). How the striatum processes cortical inputs is central to the function of the basal ganglia.
Inotropic Effects of Purines and Pyrimidines on the Isolated Heart
Authors: N. M. BUCKLEY, K. K. TSUBOI, N. J. ZEIG
Journal: Circulation Research (1961)

Hypoxanthine, guanine, thymine, and uracil were found to be positively inotropic for failing left ventricle preparations of the dog heart. Inosine, guanosine, thymidine, uridine, and their corresponding bases were found to be positively inotropic for failing rabbit hearts perfused with an artificial medium. Adenosine and cytidine and their corresponding bases were found to be negatively inotropic. Inosine, guanosine, uridine, and their constituent bases, and thymine were found to be positively inotropic for nonfailing rabbit hearts perfused with an artificial medium. Compounds that had hydroxyl groups in addition to one in the six position (xanthine, uric acid, 5-hydroxyuridine, barbituric acid and alloxan) had no consistently positive inotropic effects. The methylated purine, caffeine, was always positively inotropic. Compounds containing other substituents in the four or six position (6-mercaptopurine; 6-chloropurine; 2,4,6-trichloropyrimidine; 4-carboxypyrimidine) had no consistently positive inotropie effects. The carboxy derivative of uracil, orotic acid, was always a positive inotrope. Parent ring compounds such as purine, pyridine, and benzene had no consistent inotropic effects, while pyrimidine was always positively inotropic. Four consistently negative inotropic substances were found among all these compounds: xanthine, alloxan, 6-chloropurine, and 4-carboxypyrimidine. It was concluded that the constituent bases of naturally occurring nucleosides have cardiac effects similar to those of the nucleosides and that their inotropic effects are characteristic in both failing and nonfailing hearts.
Mesothelioma environment comprises cytokines and T-regulatory cells that suppress immune responses
Authors: J. P. J. J. Hegmans, A. Hemmes, H. Hammad, L. Boon, H. C. Hoogsteden, B. N. Lambrecht
Journal: European Respiratory Journal (2006)

Malignant mesothelioma is a cancer with dismal prognosis. The objective of the present study was to address the role of the immune system, tumour micro-environment and potential immunosuppression in mesothelioma. Expression profiles of 80 cytokines were determined in the supernatant of mesothelioma cell lines and the original patient's pleural effusion. Influx of immune effector cells was detected by immunohistochemistry. Angiogenin, vascular endothelial growth factor, transforming growth factor-β, epithelial neutrophil-activating protein-78 and several other proteins involved in immune suppression, angiogenesis and plasma extravasation could be detected in both supernatant and pleural effusion. Surrounding stroma and/or infiltrating cells were the most likely source of hepatocyte growth factor, macrophage inflammatory protein (MIP)-1δ, MIP-3α, neutrophil-activating peptide-2, and pulmonary and activation-regulated chemokine that can cause leukocyte infiltration and activation. There was a massive influx of CD4+ and CD8+ T-lymphocytes and macrophages, but not of dendritic cells, in human mesothelioma biopsies. It was further demonstrated that human mesothelioma tissue contained significant amounts of Foxp3+CD4+CD25+ regulatory T-cells. When these CD25+ regulatory T-cells were depleted in an in vivo mouse model, survival increased. Mesothelioma is infiltrated by immune effector cells but also contains cytokines and regulatory T-cells that suppress an efficient immune response. Immunotherapy of mesothelioma might be more effective when combined with drugs that eliminate or control regulatory T-cells.
Endothelin-I and angiotensin II inhibit arterial voltage-gated K+ channels through different protein kinase C isoenzymes
Authors: Richard D. Rainbow, Robert I. Norman, Diane E. Everitt, Jennifer L. Brignell, Noel W. Davies, Nicholas B. Standen
Journal: Cardiovascular Research (2009)

Voltage-gated K+ (Kv) channels of arterial smooth muscle (ASM) modulate arterial tone and are inhibited by vasoconstrictors through protein kinase C (PKC). We aimed to determine whether endothelin-1 (ET-1) and angiotensin II (AngII), which cause similar inhibition of Kv, use the same signalling pathway and PKC isoenzyme to exert their effects on Kv and to compare the involvement of PKC isoenzymes in contractile responses to these agents. Kv currents recorded using the patch clamp technique with freshly isolated rat mesenteric ASM cells were inhibited by ET-1 or AngII. Inclusion of a PKCε inhibitor peptide in the intracellular solution substantially reduced inhibition by AngII, but did not affect that by ET-1. Kv inhibition by ET-1 was reduced by the conventional PKC inhibitor Gö 6976 but not by the PKCβ inhibitor LY333531. Selective peptide inhibitors of PKCα and PKCε were linked to a Tat carrier peptide to make them membrane permeable and used to show that inhibition of PKCα prevented ET-1 inhibition of Kv current, but did not affect that by AngII. In contrast, inhibition of PKCε prevented Kv inhibition by AngII but not by ET-1. The Tat-linked inhibitor peptides were also used to investigate the involvement of PKCα and PKCε in the contractile responses of mesenteric arterial rings, showing that ET-1 contractions were substantially reduced by inhibition of PKCα, but unaffected by inhibition of PKCε. AngII contractions were unaffected by inhibition of PKCα but substantially reduced by inhibition of PKCε. ET-1 inhibits Kv channels of mesenteric ASM through activation of PKCα, while AngII does so through PKCε. This implies that ET-1 and AngII target Kv channels of ASM through different pathways of PKC-interacting proteins, so each vasoconstrictor enables its distinct PKC isoenzyme to interact functionally with the Kv channel.
Do Impotent Men With Diabetes Have More Severe Erectile Dysfunction and Worse Quality of Life Than the General Population of Impotent Patients?
Authors: David F. Penson, David M. Latini, Deborah P. Lubeck, Katrine L. Wallace, James M. Henning, Tom F. Lue
Journal: Diabetes Care (2003)

Little is known regarding how diabetic men with erectile dysfunction (ED) differ from the general population of impotent men. The primary objective of this study was to compare disease-specific health-related quality of life (HRQOL) and severity of ED in impotent men with and without diabetes.Validated functional and HRQOL questionnaires (including the International Index of Erectile Function, the Sexual Self-Efficacy Scale, and the Psychological Impact of Erectile Dysfunction scales) were administered to patients in an ED disease registry. Men with ED and a history of diabetes (n = 20) were compared with men with ED and no history of diabetes (n = 90) at baseline and at the 12-month follow-up.Diabetic impotent men reported worse erectile function and intercourse satisfaction at baseline, and ED had a greater impact on their emotional life. Diabetic men with ED had significantly different trends over time in the Erectile Function (P < 0.001), Intercourse Satisfaction (P < 0.013), Sexual Desire (P < 0.016), Overall Satisfaction (P < 0.023), and the Sexual Experience-Psychological Impact domains (P < 0.002). In addition, there was a trend toward a difference over time in the Emotional Life-Psychological Impact domain (P < 0.067).Impotent men with diabetes present with worse ED than nondiabetic men with ED, resulting in worse disease-specific HRQOL in the diabetic men. Although diabetic patients initially respond well to ED treatment, responses do not appear to be durable over time. Therefore, clinicians must provide longer-term follow-up when treating ED in diabetic patients.
Nuclear Factor of Activated T-cell Activity Is Associated with Metastatic Capacity in Colon Cancer
Authors: Manish K. Tripathi, Natasha G. Deane, Jing Zhu, Hanbing An, Shinji Mima, Xiaojing Wang, Sekhar Padmanabhan, Zhiao Shi, Naresh Prodduturi, Kristen K. Ciombor, Xi Chen, M. Kay Washington, Bing Zhang, R. Daniel Beauchamp
Journal: Cancer Research (2014)

Metastatic recurrence is the leading cause of cancer-related deaths in patients with colorectal carcinoma. To capture the molecular underpinnings for metastasis and tumor progression, we performed integrative network analysis on 11 independent human colorectal cancer gene expression datasets and applied expression data from an immunocompetent mouse model of metastasis as an additional filter for this biologic process. In silico analysis of one metastasis-related coexpression module predicted nuclear factor of activated T-cell (NFAT) transcription factors as potential regulators for the module. Cells selected for invasiveness and metastatic capability expressed higher levels of NFATc1 as compared with poorly metastatic and less invasive parental cells. We found that inhibition of NFATc1 in human and mouse colon cancer cells resulted in decreased invasiveness in culture and downregulation of metastasis-related network genes. Overexpression of NFATc1 significantly increased the metastatic potential of colon cancer cells, whereas inhibition of NFATc1 reduced metastasis growth in an immunocompetent mouse model. Finally, we found that an 8-gene signature comprising genes upregulated by NFATc1 significantly correlated with worse clinical outcomes in stage II and III colorectal cancer patients. Thus, NFATc1 regulates colon cancer cell behavior and its transcriptional targets constitute a novel, biologically anchored gene expression signature for the identification of colon cancers with high risk of metastatic recurrence.
Efforts to enforce drug laws lead to more crime, report says
Authors: A. O'Dowd
Journal: BMJ (2010)

Attempts to cut back on drug suppliers to reduce availability of illicit drugs only lead to more crime and violence, a study published on 27 April claims.

An international review that examined existing studies over the past 21 years found a strong connection between drug law enforcement efforts and increased drug related crime, killings, and gun violence.

The review was carried out by the International Centre for Science in Drug Policy, based in Canada, which is an international network of scientists, academics, and health practitioners working to improve the health and safety …
Re: Wieland BM, et al. Is There a Human Homologue to the Murine Proteolysis–Inducing Factor?
Authors: Michael J. Tisdale
Journal: Clinical Cancer Research (2008)

In Response: Wieland et al. (1) have examined the role of proteolysis-inducing factor (PIF) in human cancer cachexia by Western blotting of total urinary proteins using a monoclonal antibody, which is directed to the sulfated oligosaccharide chains (2). However, it is unlikely that they were measuring PIF, in view of the cross-reactivity of this antibody to immunoglobulin light chains. This is not surprising considering the low affinity of the antibody for PIF (Kaff 108M−1) and the limiting number of structural motifs on oligosaccharides, which in PIF bear some resemblance to chondroitin sulfate (2). Although the antibody is monoclonal, it was produced by fusion of splenocytes from mice bearing the MAC16 tumor without administration of antigen (3). Most recent studies have either confirmed that the band appearing at 24 kDa in the Western blots was PIF by using an antibody to the polypeptide core (4) or have fractionated the urine by capillary electrophoresis before mass spectrometry (5). These studies were not referenced in the above article, which is surprising because the results of the latter study showed the opposite result, which is cancer patients who were positive for PIF experienced weight loss, whereas PIF-negative patients gained weight (5). In addition to the lack of confirmation that the material being measured was PIF, there seems to be only one measurement of the PIF status of the patients. This is important because in the longitudinal studies (5), four repeated measures were made during a 2.5-year period, and there was a change in PIF status in 41% of the patients with 19% changing from negative to positive, 8% changing from positive to negative, and 14% varying during the course of the study. This change in PIF status could have happened in the above study. PIF concentrations in urine are very low (500 ng/L, representing 5 × 10−4% of total cellular protein), and it is unlikely to be in the major bands as reported. However, other workers (6) have successfully purified PIF from human urine and have shown it to be identical to recombinant PIF.The authors question whether glycosylated PIF could exist based on the lack of a conventional N- and O-glycosylation sequence in the PIF core peptide. However, fully glycosylated recombinant PIF has been reported (6), and glycosylated PIF has been detected in bone, liver, and lymph node metastases as well as urine of cachectic patients using an antibody to both the core peptide, and to the oligosaccharide chains (4).
Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme
Authors: Jeffrey R Curtis, Eun Bong Lee, Irina V Kaplan, Kenneth Kwok, Jamie Geier, Birgitta Benda, Koshika Soma, Lisy Wang, Richard Riese
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To further assess the potential role of Janus kinase inhibition in the development of malignancies, we performed an integrated analysis of data from the tofacitinib RA clinical development programme. <h3>Methods</h3> Malignancy data (up to 10 April 2013) were pooled from six phase II, six Phase III and two long-term extension (LTE) studies involving tofacitinib. In the phase II and III studies, patients with moderate-to-severe RA were randomised to various tofacitinib doses as monotherapy or with background non-biological disease-modifying antirheumatic drugs (DMARDs), mainly methotrexate. The LTE studies (tofacitinib 5 or 10 mg twice daily) enrolled patients from qualifying prior phase I, II and III index studies. <h3>Results</h3> Of 5671 tofacitinib-treated patients, 107 developed malignancies (excluding non-melanoma skin cancer (NMSC)). The most common malignancy was lung cancer (n=24) followed by breast cancer (n=19), lymphoma (n=10) and gastric cancer (n=6). The rate of malignancies by 6-month intervals of tofacitinib exposure indicates rates remained stable over time. Standardised incidence ratios (comparison with Surveillance, Epidemiology and End Results) for all malignancies (excluding NMSC) and selected malignancies (lung, breast, lymphoma, NMSC) were within the expected range of patients with moderate-to-severe RA. <h3>Conclusions</h3> The overall rates and types of malignancies observed in the tofacitinib clinical programme remained stable over time with increasing tofacitinib exposure.
Multiple risk factors related to familial predisposition to anterior cruciate ligament injury: fraternal twin sisters with anterior cruciate ligament ruptures
Authors: T E Hewett, T R Lynch, G D Myer, K R Ford, R C Gwin, R S Heidt
Journal: British Journal of Sports Medicine (2009)

Objective A multifactorial combination of predictors may increase anterior cruciate ligament (ACL) injury risk in athletes. The objective of this twin study was to examine these risk factors to identify commonalities in risk factors that predisposed female fraternal twins to ACL injury. Methods Female twins in high-risk sports were prospectively measured prior to an injury for neuromuscular control using three-dimensional motion analysis during landing, hamstrings and quadriceps muscular strength on a dynamometer and joint laxity using a modified Beighton–Horan index and a Compu-KT arthrometer. Intraoperative measures of femoral intercondylar notch width were recorded during ACL reconstruction. Results Abduction angles were increased at one knee in both of the twin sister athletes relative to uninjured controls at initial contact and at maximum displacement during landing. The twin female athletes that went on to ACL injury also demonstrated decreased peak knee flexion motion at both knees than uninjured females during landing. The twin athletes also had increased joint laxity and decreased hamstrings to quadriceps (H/Q) torque ratios compared to controls. Femoral intercondylar notch widths were also below the control mean in the twin siblings. Conclusions Prescreened mature female twins that subsequently experienced ACL injury demonstrated multiple potential risk factors including: increased knee abduction angles, decreased knee flexion angles, increased general joint laxity, decreased H/Q ratios and femoral intercondylar notch width.
Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase–dependent DC functions and regulates experimental graft-versus-host disease in mice
Authors: Pavan Reddy, Yaping Sun, Tomomi Toubai, Raimon Duran-Struuck, Shawn G. Clouthier, Elizabeth Weisiger, Yoshinobu Maeda, Isao Tawara, Oleg Krijanovski, Erin Gatza, Chen Liu, Chelsea Malter, Paolo Mascagni, Charles A. Dinarello, James L.M. Ferrara
Journal: Journal of Clinical Investigation (2008)

Histone deacetylase (HDAC) inhibitors are antitumor agents that also have antiinflammatory properties. However, the mechanisms of their immunomodulatory functions are not known. We investigated the mechanisms of action of 2 HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and ITF 2357, on mouse DC responses. Pretreatment of DCs with HDAC inhibitors significantly reduced TLR-induced secretion of proinflammatory cytokines, suppressed the expression of CD40 and CD80, and reduced the in vitro and in vivo allostimulatory responses induced by the DCs. In addition, injection of DCs treated ex vivo with HDAC inhibitors reduced experimental graft-versus-host disease (GVHD) in a murine allogeneic BM transplantation model. Exposure of DCs to HDAC inhibitors increased expression of indoleamine 2,3-dioxygenase (IDO), a suppressor of DC function. Blockade of IDO in WT DCs with siRNA and with DCs from IDO-deficient animals caused substantial reversal of HDAC inhibition–induced in vitro suppression of DC-stimulated responses. Direct injection of HDAC inhibitors early after allogeneic BM transplantation to chimeric animals whose BM-derived cells lacked IDO failed to protect from GVHD, demonstrating an in vivo functional role for IDO. Together, these data show that HDAC inhibitors regulate multiple DC functions through the induction of IDO and suggest that they may represent a novel class of agents to treat immune-mediated diseases.
TURPENTINE IN THE TREATMENT OF PURPURA
Authors: Wm. Smith
Journal: BMJ (1853)

SElL SMomsch.She had menstruated scantily at nine, but only twice since.Feet very cold, and bowels constipated.By the application of a galbanum plaster to the throat, milk diet, and exercise, cured.Bright* mentions the case of a female brought into Guy's Hospital, suffering from stricture of several weeks' duration.The introduction of a probang-broug,ht on a fit of hysteria.SILCTURE FRO'M GOUT.A case fell under my notice a short time back, where a person, while suffering from an attack of gouty spmasm of the stomach, everything was re- jected the moment it reachehd the lower part of the pharynx.Mlr. Watson (quoted by llowship) speaks of a case occur- ring in a gouty gentleman.Courant describes a case wvhere it preceded the paroxysm of gout.STRICTURE FROMI SLPPRESSION OF CUTANEOUS ERUIPTIONS.Manclerc,t a Case in a nervous feumale, where the suppression of an eruption on the back of the hand, by an astringent application, was followeJ by vomniting anzd spasmodic con- striction of the throat.Aird § mentions the casc of his son, aged 18, in whom the sudden disappearance of a ehronic eruptiojn was followed by swelling and pain in the umilbilical and hypochondriac regions, and spasm of the (esophagus.STRICTURE FROMI AFFECTIONS OP TIlE MINiD.An instance