tbuckley/cabot-search huggingface dataset:
Safety of a new, single, integrated, closed photopheresis system in patients with cutaneous T-cell lymphoma
Authors: E. Bisaccia, E.C. Vonderheid, L. Geskin
Journal: British Journal of Dermatology (2009)

Journal Article Safety of a new, single, integrated, closed photopheresis system in patients with cutaneous T‐cell lymphoma Get access E. Bisaccia, E. Bisaccia Morristown Memorial Hospital, Morristown, NJ 07960, U.S.A. Correspondence: Emil Bisaccia. E‐mail: emil.bisaccia@atlantichealth.org Search for other works by this author on: Oxford Academic Google Scholar E.C. Vonderheid, E.C. Vonderheid Johns Hopkins University, Baltimore, MD, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar L. Geskin L. Geskin University of Pittsburgh, Pittsburgh, PA, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 161, Issue 1, 1 July 2009, Pages 167–169, https://doi.org/10.1111/j.1365-2133.2009.09081.x Published: 01 July 2009
Divergent roles of nitrergic and prostanoid pathways in chronic joint inflammation
Authors: S M Day
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Nitrergic and prostanoid pathways have both been implicated in inflammatory processes. <b>Objective:</b> To investigate their respective contributions in a rat model of chronic arthritis. <b>Methods:</b> Male Wistar rats (n = 4–6/group) received either an intra-articular injection of 2% carrageenan/4% kaolin (C/K) or intra- and periarticular injections of Freund's complete adjuvant (FCA; 10 mg/ml <i>M tuberculosis</i>). Joint diameter, urinary nitric oxide metabolites (NO<sub>x</sub>), and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) levels were measured as indices of the inflammatory process. A prophylactic and therapeutic (day 5) dose ranging study of an inducible nitric oxide synthase inhibitor, l-<i>N</i>-(1-iminoethyl)-lysine (l-NIL), and a cyclo-oxygenase-2 (COX-2) inhibitor, SC-236, was performed with the drugs given subcutaneously. Submaximal doses were identified and used for combination studies. Appropriate vehicle controls were included. <b>Results:</b>l-NIL and SC-236 dose dependently inhibited C/K induced acute joint swelling, the magnitude being greatest when they were given in combination. Both prophylactic and therapeutic administration of SC-236 in the FCA induced model of chronic arthritis produced a dose dependent reduction in all the measures assessed. However, although l-NIL demonstrated similar dose dependent inhibition of urinary NO<sub>x</sub> and PGE<sub>2</sub> levels, joint swelling was significantly exacerbated in this model. Co-administration of the inhibitors nullified the benefits of SC-236. <b>Conclusion:</b> Whereas COX-2 derived prostaglandins are proinflammatory in both acute and chronic joint inflammation, NO seems to have divergent roles, being anti-inflammatory in chronic and proinflammatory in acute joint inflammation.
Transfer of services from NHS to private provider was "unmitigated disaster," report says
Authors: G. Iacobucci
Journal: BMJ (2015)

The botched transfer of specialist dermatology services from a leading NHS hospital to a private company has been described as “an unmitigated disaster” by an independent review.

The investigation found that an “adversarial” relationship developed between local commissioners and providers after NHS Rushcliffe Clinical Commissioning Group decided to transfer services from Nottingham University Hospitals NHS Trust to the private provider Circle Health in 2012.1 The decision was based on an assumption that many staff would also transfer.

The review, commissioned by the clinical commissioning group and led by Chris Clough, former chairman of the National Clinical Advisory Team, said that the handling of the transfer had led to the near collapse of local services because of ongoing problems with staff retention and recruitment.

“Dermatology services in Nottingham are in crisis due to the inability to recruit to substantive posts and the on-going reliance on locum posts at Circle,” it said.

The problems surfaced after the clinical commissioning group awarded a contract to Circle to provide a range of services at the Nottingham Treatment Centre (an independent sector treatment centre), including adults’ and children’s dermatology. Circle’s successful bid was based on an expectation …
Re: Prostate Cancer in Fathers With Fewer Male Offspring: the Jerusalem Perinatal Study Cohort
Authors: W. H. James
Journal: JNCI Journal of the National Cancer Institute (2007)

We read with interest the recent article by Harlap et al. ( 1 ).The authors reported that, among 712 men with prostate cancer, those with only daughters had an increased risk of prostate cancer, compared with men with at least one son (adjusted relative risk = 1.40, 95% confidence interval [CI] = 1.20 to 1.64, P <.0001).The results prompted the authors to speculate that a Y chromosome locus may be involved in prostate cancer risk in the population they studied.Because the study of Harlap et al. was small, we decided to replicate the analyses taking advantage of the last update of the Swedish Family-Cancer Database.The Database has been described in detail elsewhere ( 2 , 3 ).In our analyses, more than 3.1 million men were followed from birth of their fi rst offspring, immigration date, or fi rst year of the study (1961), whichever came latest, until death, diagnosis of any cancer, emigration, or December 31, 2004, whichever came fi rst.We identifi ed 120 812 men with invasive prostate cancer diagnosed at the age of 32 -99 years Table 1 .Relative risk of prostate cancer in men with offspring in the Swedish Family-Cancer Database by numbers of total offspring and male offspring * Total offspring, No. Male offspring, No.
Traumatic Injuries in Developing Countries
Authors: Kerry-Ann A Stewart, Reinou S Groen, Thaim B Kamara, Mina M Farahzad, Mohamed Samai, Laura D Cassidy, Adam L Kushner, Sherry M Wren
Journal: JAMA Surgery (2013)

To use a nationwide household survey tool to provide an estimate of injury prevalence, mechanisms of traumatic injuries, and number of injury-related deaths in a low-income country.
Regulation of Trypanosoma cruzi infections in vitro and in vivo by transforming growth factor beta (TGF-beta).
Authors: J S Silva, D R Twardzik, S G Reed
Journal: The Journal of Experimental Medicine (1991)

The effects of transforming growth factor beta (TGF-beta) on interferon gamma-mediated killing of the intracellular protozoan parasite Trypanosoma cruzi and on the course of T. cruzi infection in mice were investigated. Spleen cells from mice with acute T. cruzi infections were found to produce elevated levels of biologically active TGF-beta in vitro, and the possibility that TGF-beta may mediate certain aspects of T. cruzi infection was then addressed. When mouse peritoneal macrophages were treated with TGF-beta in vitro, the ability of IFN-gamma to activate intracellular inhibition of the parasite was blocked. This occurred whether cells were treated with TGF-beta either before or after IFN-gamma treatment. TGF-beta treatment also blocked the T. cruzi-inhibiting effects of IGN-gamma on human macrophages. Additionally, treatment of human macrophages with TGF-beta alone led to increased parasite replication in these cells. The effects of TGF-beta on T. cruzi infection in vivo were then investigated. Susceptible C57BL/6 mice developed higher parasitemias and died earlier when treated with TGF-beta during the course of infection. Resistant C57BL/6 x DBA/2 F1 mice treated with TGF-beta also had increased parasitemias, and 50% mortality, compared with no mortality in infected, saline-treated controls. A single dose of TGF-beta, given at the time of infection, was sufficient to significantly decrease resistance to infection in F1 mice and to exacerbate infection in susceptible C57BL/6 mice. Furthermore, a single injection of TGF-beta was sufficient to counter the in vivo protective effects of IFN-gamma. We conclude that TGF-beta, produced during acute T. cruzi infection in mice, is a potent inhibitor of the effects of macrophage activating cytokines in vivo and in vitro and may play a role in regulating infection.
Functional diversification of sonic hedgehog paralog enhancers identified by phylogenomic reconstruction
Authors: Yavor Hadzhiev, Michael Lang, Raymond Ertzer, Axel Meyer, Uwe Strähle, Ferenc Müller
Journal: Genome biology (2007)

Cis-regulatory modules of developmental genes are targets of evolutionary changes that underlie the morphologic diversity of animals. Little is known about the 'grammar' of interactions between transcription factors and cis-regulatory modules and therefore about the molecular mechanisms that underlie changes in these modules, particularly after gene and genome duplications. We investigated the ar-C midline enhancer of sonic hedgehog (shh) orthologs and paralogs from distantly related vertebrate lineages, from fish to human, including the basal vertebrate Latimeria menadoensis.We demonstrate that the sonic hedgehog a (shha) paralogs sonic hedgehog b (tiggy winkle hedgehog; shhb) genes of fishes have a modified ar-C enhancer, which specifies a diverged function at the embryonic midline. We have identified several conserved motifs that are indicative of putative transcription factor binding sites by local alignment of ar-C enhancers of numerous vertebrate sequences. To trace the evolutionary changes among paralog enhancers, phylogenomic reconstruction was carried out and lineage-specific motif changes were identified. The relation between motif composition and observed developmental differences was evaluated through transgenic functional analyses. Altering and exchanging motifs between paralog enhancers resulted in reversal of enhancer specificity in the floor plate and notochord. A model reconstructing enhancer divergence during vertebrate evolution was developed.Our model suggests that the identified motifs of the ar-C enhancer function as binary switches that are responsible for specific activity between midline tissues, and that these motifs are adjusted during functional diversification of paralogs. The unraveled motif changes can also account for the complex interpretation of activator and repressor input signals within a single enhancer.
Tumor necrosis factor stimulates amino acid transport in plasma membrane vesicles from rat liver.
Authors: A J Pacitti, Y Inoue, W W Souba
Journal: Journal of Clinical Investigation (1993)

Severe infection is characterized by a translocation of amino acids from the periphery to the liver, an event that is mediated in part by cytokines such as tumor necrosis factor-alpha (TNF). We investigated the activities of Na(+)-dependent transport systems A, ASC, and N in hepatic plasma membrane vesicles (HPMVs) prepared from rats treated with TNF in vivo. TNF did not alter sodium uptake but resulted in time- and dose-dependent fivefold and 50% maximal increases in system A and system N activity, respectively, in HPMVs secondary to an increase in the transport Vmax. Maximal increases in transport were observed 4 h after exposure to TNF and had returned to basal levels within 24 h. Similarly, system ASC activity was stimulated 80% in HPMVs from rats treated with TNF. Incubation of HPMVs from normal rats in vitro with TNF did not alter transport activity. Pretreatment of animals with the glucocorticoid receptor antagonist RU 38486 attenuated the TNF-induced enhancement in transport activity by 50%. The marked increase in Na(+)-dependent amino acid transport activity by TNF is mediated in part by the glucocorticoid hormones and represents an important mechanism underlying the accelerated hepatic amino acid uptake that occurs during critical illness.
Effect of nasal CPAP on ventilatory drive in normocapnic and hypercapnic patients with obstructive sleep apnoea syndrome
Authors: CC Lin
Journal: European Respiratory Journal (1994)

The purpose of this study was to evaluate the effect of nasal continuous positive airway pressure (CPAP) on the abnormal ventilatory drive in hypercapnic patients with the obstructive sleep apnoea syndrome (OSAS). Six patients with hypercapnic OSAS (Group I) and 24 patients with eucapnic OSAS (Group II) were studied. All patients had arterial blood gas analysis, overnight sleep studies, and an assessment of ventilatory drive (progressive hyperoxic hypercapnic response and progressive isocapnic hypoxic ventilatory response) prior to and during nasal CPAP therapy (at 2 weeks and 1 month of treatment). Nasal CPAP effectively improved the hypopnoea/apnoea index in both groups (Group I: 87 +/- 14 vs 8 +/- 4; Group II: 63 +/- 17 vs 6 +/- 3). Both hypercapnic and hypoxic ventilatory drive before treatment were significantly impaired in Group I as compared to Group II. Both the slope and baseline level of the ventilatory response and the mouth occlusion pressure (P0.1) improved significantly after 2 weeks of nasal CPAP therapy in Group I, with normalization of arterial carbon dioxide tension (PaCO2) (6.3 +/- 0.2 to 5.2 +/- 0.4 kPa). We conclude that it is possible to completely correct the abnormal ventilatory drive in hypercapnic OSAS patients within 14 days of initiating nasal CPAP therapy.
Lack of Association Between Neuroleptic Malignant Syndrome and Polymorphisms in the 5-HT<sub>1A</sub>and 5-HT<sub>2A</sub>Receptor Genes
Authors: C Kawanishi, T Hanihara, Y Shimoda, K Suzuki, N Sugiyama, H Onishi, T Miyakawa, Y Yamada, K Kosaka
Journal: American Journal of Psychiatry (1998)

The molecular basis of neuroleptic malignant syndrome is unclear, but studies suggest that genetic factors are involved in its pathogenesis. Considering possible involvement of the serotonergic system in neuroleptic malignant syndrome, the authors examined the association between neuroleptic malignant syndrome and polymorphisms of the 5-HT1A and 5-HT2A receptor genes.The authors examined the frequencies of gene polymorphisms in the 5-HT1A (Arg219Leu) and 5-HT2A (Thr25Asn and His452Tyr) receptor genes in 29 patients previously diagnosed with neuroleptic malignant syndrome, 94 neuroleptic-treated patients with schizophrenia who had no history of neuroleptic malignant syndrome, and 94 healthy comparison subjects. Polymerase chain reaction and restriction fragment length polymorphism analyses were used to screen gene mutations.No polymorphic allele was detected in the patients who had experienced the neuroleptic malignant syndrome.The authors cannot conclude that polymorphisms in the 5-HT1A and 5HT2A receptor genes are factors determining susceptibility to the neuroleptic malignant syndrome.
Cycloxygenase-2 Is Expressed in Vasculature of Normal and Ischemic Adult Human Kidney and Is Colocalized with Vascular Prostaglandin E2 EP4 Receptors
Authors: Karina L. Therland, Jane Stubbe, Helle C. Thiesson, Peter D. Ottosen, Steen Walter, Grith L. Sørensen, Ole Skøtt, Boye L. Jensen
Journal: Journal of the American Society of Nephrology (2004)

The study was performed to elucidate the distribution and cellular localization of cyclooxygenase (COX)-2 in human kidney and to address localization of downstream targets for COX-derived prostanoids. Cortex and outer and inner medulla tissue were obtained from control kidneys (cancer specimens), kidneys with arterial stenosis, and kidneys of patients who received angiotensin II inhibition or acetylsalicylic acid. Ribonuclease protection assay and Western blot test revealed that COX-1 and -2 mRNA and protein were expressed in all regions of human kidney (mRNA ratio, cortex:outer medulla:inner medulla COX-1 1:3:20 and COX-2 1:1:3). In adult kidney, immunohistochemical labeling for COX-2 was associated with smooth muscle cells in pre- and postglomerular vessels and with endothelium, particularly in vasa recta and medullary capillaries. Western blot test confirmed COX-2 expression in renal artery. COX-2 had a similar localization in fetal kidney and was additionally observed in Henle's loop and macula densa. Human tissue arrays displayed COX-2 labeling of vascular smooth muscle in multiple extrarenal tissues. Vascular COX-2 expression was significantly increased in kidneys with arterial stenosis. COX-1 was colocalized with microsomal prostaglandin E(2) synthase (PGES) in collecting ducts, and PGES was also detected in macula densa cells. Vascular COX-2 was colocalized with prostaglandin E(2) EP4 receptors but not with EP2 receptors. Thus, renovascular COX-2 expression was a constitutive feature encountered in human kidneys at all ages, whereas COX-2 was seen in macula densa only in fetal kidney. Vascular COX-2 activity in human kidney and extrarenal tissues may support blood flow and affect vascular wall-blood interaction.
Role and Relevance of TrkB Mutations and Expression in Non–Small Cell Lung Cancer
Authors: Taishi Harada, Yasushi Yatabe, Masafumi Takeshita, Takaomi Koga, Tokujiro Yano, Yisong Wang, Giuseppe Giaccone
Journal: Clinical Cancer Research (2011)

TrkB has been involved in poor cancer outcome. TrkB mutations have been reported in non-small cell lung cancer. In this study, we aimed at characterizing the role of three potentially sensitizing TrkB mutations previously reported in lung cancer.We characterized three activation loop mutants of TrkB (M713I, R715G, and R734C) in terms of pathway activation/phosphorylation, migration, anchorage-independent growth, and sensitivity to a Trk inhibitor, using NIH3T3 cells and Baf3 cells. We also sequenced the tyrosine kinase domain of TrkB in a large number of lung cancer samples of East-Asian origin and cell lines.None of the mutants were constitutively active in NIH3T3 transformation and migration assays. M713I and R734C mutants showed low levels of autophosphorylation in comparison with wild-type TrkB. Although R715G showed similar level of autophosphorylation to wild-type TrkB on brain-derived neurotrophic factor stimulation, the mutant was not as competent as wild-type TrkB in supporting interleukin-3-independent growth of Baf3 cells. In addition, the Trk inhibitor AZD6918 inhibited wild-type TrkB-induced cell migration and cell growth, whereas the mutants were relatively resistant to the Trk inhibitor compared with wild-type TrkB. We could not confirm the presence of nonsynonymous mutation in 78 lung cancer samples and 29 cell lines.Wild-type, but not mutant, TrkB enhances cell migration and transformation. Our study suggests that TrkB mutations should not be used for selection of patients with lung cancer treated with Trk inhibitors. High expression of wild-type TrkB might be beneficial for studies of Trk inhibitors.
Hereditary Deficiency of gp91 <sup>phox</sup> Is Associated With Enhanced Arterial Dilatation
Authors: Francesco Violi, Valerio Sanguigni, Roberto Carnevale, Alessandro Plebani, Paolo Rossi, Andrea Finocchi, Claudio Pignata, Domenico De Mattia, Baldassarre Martire, Maria Cristina Pietrogrande, Silvana Martino, Eleonora Gambineri, Anna Rosa Soresina, Pasquale Pignatelli, Francesco Martino, Stefania Basili, Lorenzo Loffredo
Journal: Circulation (2009)

Background— NADPH oxidase is believed to modulate arterial tone, but its role in humans is still unclear. The objective of this study was to evaluate whether NADPH oxidase is involved in flow-mediated arterial dilation (FMD). Methods and Results— Twenty-five patients with hereditary deficiency of gp91 phox , the catalytic core of NADPH oxidase, (X-CGD), 25 healthy subjects, and 25 obese patients matched for sex and age were recruited. FMD, platelet gp91 phox , serum levels of nitrite and nitrate as markers of nitric oxide generation, oxidized low-density lipoprotein, and urinary excretion of isoprostanes as markers of oxidative stress were determined. Platelet gp91 phox expression was downregulated in X-CGD patients (1.0±0.8 mean fluorescence; P &lt;0.001) and upregulated in obese patients (4.1±2.2 mean fluorescence; P =0.01) compared with healthy subjects (2.9±1.7 mean fluorescence). Urinary excretion of isoprostanes was reduced in X-CGD patients (41.7±33.3 pg/mg creatinine; P =0.04) and increased in obese patients (154.4±91 pg/mg creatinine; P &lt;0.001) compared with healthy subjects (69.5±52.4 pg/mg creatinine). Obese patients had higher serum oxidized low-density lipoprotein than healthy subjects (35.3±6.7 versus 24.8±9.8 U/L; P &lt;0.001) and X-CGD patients (28.5±7.2 U/L; P &lt;0.001). X-CGD patients had significantly higher FMD (14.7±5.9%) compared with healthy subjects (7.9±2.5%; P &lt;0.001); obese patients had lower FMD (5.3±3.0%; P =0.028) compared with healthy subjects. Serum nitrite and nitrate levels were significantly higher in patients with X-CGD (36.0±10.8 μmol/L; P =0.016) and lower in obese patients (9.3±11.0 μmol/L; P =0.001) compared with healthy subjects (27.1±19.1 μmol/L). Serum nitrite and nitrate levels significantly correlated with FMD ( R s =0.403, P &lt;0.001) and platelet gp91 phox ( R s =−0.515, P &lt;0.001). FMD inversely correlated with platelet gp91 phox ( R s =−0.502, P &lt;0.001) and isoprostanes ( R s =−0.513, P &lt;0.001). Conclusion— This study provides the first evidence that, in humans, gp91 phox is implicated in the modulation of arterial tone.
Cholestatic expression pattern of sinusoidal and canalicular organic anion transport systems in primary cultured rat hepatocytes
Authors: Jane S. Rippin, Bruno Hagenbuch, Peter J. Meier, Bruno Stieger
Journal: Hepatology (2001)

To maintain ongoing vectorial bile secretion, hepatocytes localize distinct transport systems at their basolateral and canalicular membrane domains. Here we compare the expression of the basolateral Na + –taurocholate cotransporter (Ntcp) and organic anion transporting polypetides 1 and 2 (Oatp1, Oatp2) and the canalicular bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2) in primary cultured rat hepatocytes. During 72 hours of culturing time the messenger RNA (mRNA) and protein levels of Ntcp and Oatp1 decreased in parallel to 2% to 7% of initial values at 3 hours. Although Oatp2 mRNA exhibited a similar down–regulation to 4%, Oatp2 protein and function were maintained at 25% to 47% of initial values. Furthermore, Bsep and Mrp2 protein levels were maintained at about 50%, while the Mrp2 mRNA showed a transient up–regulation to 154% at 24 and 48 hours. Also, induction of Mrp1 mRNA and protein was observed starting after 24 hours. These results indicate transcriptional down–regulation or decreased mRNA stability of Ntcp and Oatp1, transcriptional and posttranslational regulation of Oatp2, Bsep, and Mrp2 and transcriptional up–regulation of Mrp1 in primary cultured hepatocytes. Furthermore, and most importantly, the observed changes in transporter expression closely resemble the altered transporter phenotypes of cholestatic and proliferating hepatocytes in vivo , thus indicating that primary cultured hepatocytes acquire a cholestatic phenotype, and that the transporter expression might be a suitable differentiation marker for maintenance of hepatocytes in vitro .
Killer-cell Immunoglobulin-like Receptor gene linkage and copy number variation analysis by droplet digital PCR
Authors: Chrissy h Roberts, Wei Jiang, Jyothi Jayaraman, John Trowsdale, Martin J Holland, James A Traherne
Journal: Genome Medicine (2014)

The Killer-cell Immunoglobulin-like Receptor (KIR) gene complex has considerable biomedical importance. Patterns of polymorphism in the KIR region include variability in the gene content of haplotypes and diverse structural arrangements. Droplet digital PCR (ddPCR) was used to identify different haplotype motifs and to enumerate KIR copy number variants (CNVs). ddPCR detected a variety of KIR haplotype configurations in DNA from well-characterized cell lines. Mendelian segregation of ddPCR-estimated KIR2DL5 CNVs was observed in Gambian families and CNV typing of other KIRs was shown to be accurate when compared to an established quantitative PCR method.