tbuckley/cabot-search huggingface dataset:
Randomized, double-blind, prospective study to compare topical 5-aminolaevulinic acid methylester with topical 5-aminolaevulinic acid photodynamic therapy for extensive scalp actinic keratosis
Authors: F.J. Moloney, P. Collins
Journal: British Journal of Dermatology (2007)

5-aminolaevlinic acid methylester (MAL) and 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) are both effective treatment options for actinic keratosis (AK). While MAL is significantly more expensive than ALA, no studies have directly compared their efficacy in the treatment of extensive scalp AK.To compare the efficacy and adverse effects of MAL-PDT with ALA-PDT in the treatment of scalp AK.Sixteen male patients aged 59-87 years with extensive scalp AK were randomized into a double-blind, split-scalp prospective study. Two treatment fields were defined (right and left frontoparietal scalp) and treated 2 weeks apart. These fields were randomized to receive either MAL or ALA as first or second treatment. MAL cream was applied for 3 h; 20% ALA cream was applied for 5 h. A blinded observer assessed efficacy comparing AK counts before and 1 month after treatment. Pain was assessed using a visual analogue scale at 3, 6, 12 and 16 min.Fifteen patients completed treatment to both fields. There was a mean reduction from baseline in AK counts with the use of ALA-PDT of 6.2 +/- 1.9 compared with 5.6 +/- 3.2 with MAL-PDT (P = 0.588). All patients experienced pain which was of greater intensity in the ALA-treated side at all time points: 3 min (P = 0.151), 6 min (P = 0.085), 12 min (P = 0.012) and 16 min (P = 0.029). Similarly, duration of discomfort post-procedure persisted for longer following treatment with ALA when compared with MAL-PDT (P = 0.044).This study demonstrates that both ALA-PDT and MAL-PDT result in a significant reduction in scalp AK. There is no significant difference in efficacy. However, ALA-PDT is more painful than MAL-PDT in the treatment of extensive scalp AK.
Incidence and Progression of Diabetic Retinopathy During 17 Years of a Population-Based Screening Program in England
Authors: Colin D. Jones, Richard H. Greenwood, Aseema Misra, Max O. Bachmann
Journal: Diabetes Care (2012)

To estimate the incidence of diabetic retinopathy in relation to retinopathy grade at first examination and other prognostic characteristics.This was a dynamic cohort study of 20,686 people with type 2 diabetes who had annual retinal photography up to 14 times between 1990 and 2006. Cumulative and annual incidence rates were estimated using life tables, and risk factors for progression were identified using Cox regression analysis.Of 20,686 patients without proliferative diabetic retinopathy (PDR) or sight-threatening maculopathy at their first retinal examination (baseline), 16,444 (79%) did not have retinopathy, 3,632 (18%) had nonproliferative retinopathy, and 610 (2.9%) had preproliferative retinopathy. After 5 years, few patients without retinopathy at baseline developed preproliferative retinopathy (cumulative incidence 4.0%), sight-threatening maculopathy (0.59%), or PDR (0.68%); after 10 years, the respective cumulative incidences were 16.4, 1.2, and 1.5%. Among those with nonproliferative (background) retinopathy at baseline, after 5 years [corrected] 23% developed preproliferative retinopathy, 5.2% developed maculopathy, and 6.1% developed PDR; after 10 years, the respective cumulative incidences were 53%, 9.6%, and 11%. Patients with nonproliferative retinopathy at baseline were five times more likely to develop preproliferative, PDR, or maculopathy than those without retinopathy at baseline (adjusted hazard ratio 5.0 [95% CI 4.4-5.6]).Few patients without diabetic retinopathy at the initial screening examination developed preproliferative retinopathy, PDR, or sight-threatening maculopathy after 5-10 years of follow-up. Screening intervals longer than a year may be appropriate for such patients.
Rate of CRL4CRBN substrate Ikaros and Aiolos degradation underlies differential activity of lenalidomide and pomalidomide in multiple myeloma cells by regulation of c-Myc and IRF4
Authors: C C Bjorklund, L Lu, J Kang, P R Hagner, C G Havens, M Amatangelo, M Wang, Y Ren, S Couto, M Breider, Y Ning, A K Gandhi, T O Daniel, R Chopra, A Klippel, A G Thakurta
Journal: Blood Cancer Journal (2015)

Recent discoveries suggest that the critical events leading to the anti-proliferative activity of the IMiD immunomodulatory agents lenalidomide and pomalidomide in multiple myeloma (MM) cells are initiated by Cereblon-dependent ubiquitination and proteasomal degradation of substrate proteins Ikaros (IKZF1) and Aiolos (IKZF3). By performing kinetic analyses, we found that the downregulation or proteasomal degradation of Ikaros and Aiolos led to specific and sequential downregulation of c-Myc followed by IRF4 and subsequent growth inhibition and apoptosis. Notably, to ensure growth inhibition and cell death, sustained downregulation of Ikaros and Aiolos, c-Myc or IRF4 expression was required. In addition, we found that the half-maximal rate, rather than the final extent of Ikaros and Aiolos degradation, correlated to the relative efficacy of growth inhibition by lenalidomide or pomalidomide. Finally, we observed that all four transcription factors were elevated in primary MM samples compared with normal plasma cells. Taken together, our results suggest a functional link between Ikaros and Aiolos, and the pathological dysregulation of c-Myc and IRF4, and provide a new mechanistic understanding of the relative efficacy of lenalidomide and pomalidomide based on the kinetics of substrate degradation and downregulation of their downstream targets.
Regulation of energy balance by brown adipose tissue: at least three potential roles for physical activity
Authors: Jonatan R Ruiz, Borja Martinez-Tellez, Guillermo Sanchez-Delgado, Concepcion M Aguilera, Angel Gil
Journal: British Journal of Sports Medicine (2015)

Brown adipose tissue (BAT) has the ability to oxidise glucose and lipids, and dissipate energy in the form of heat.1 Thus, it could provide one method to influence energy balance—and therefore, be a player in the fight against obesity and type 2 diabetes.

BAT is highly regulated by the sympathetic nervous system (SNS) to increase body temperature when mammals are exposed to cold. The heat production is mediated by uncoupling protein 1 (UCP-1), an inner-membrane mitochondrial protein exclusively expressed in BAT.1 Dogma was that BAT was only present in newborns. However, radiologists using the radiotracer 18F-fluorodeoxyglucose in positron emission tomography (PET)/computed tomography to detect metabolically active tumours, found competing areas in the supraclavicular, thoracic spine and neck regions with high rates of glucose uptake. The significance of BAT for human physiology was recognised in 2007.2

Recently, another type of cells called brown-in-white (BRITE) or beige cells, in white adipose tissue (WAT) have been found.3 BRITE cells possess a multilocular morphology, enriched mitochondria and express the brown adipocyte-specific UCP-1.

A potential clinical implication of activating BAT relates to the stimulation of resting energy expenditure and diet-induced thermogenesis. In humans, the thermogenic response to a meal is higher in those possessing BAT. It has been estimated that 50 g of activated BAT might translate to increase ∼5% of resting …
ALLOTYPE EXCLUSION IN UNIFORM RABBIT ANTIBODY TO STREPTOCOCCAL CARBOHYDRATE
Authors: Thomas J. Kindt, Charles W. Todd, Klaus Eichmann, Richard M. Krause
Journal: The Journal of Experimental Medicine (1970)

Rabbit antibodies to streptococcal polysaccharide are described which show selectivity of expression of the allotypic specificities on both the heavy (H) and light (L) chains. One of these antibodies binds weakly to Sephadex. A purification method based on this binding has yielded antibody completely lacking any group a allotypic marker on its H chains.
Palmitoylation of ATP-Binding Cassette Transporter A1 Is Essential for Its Trafficking and Function
Authors: Roshni R. Singaraja, Martin H. Kang, Kuljeet Vaid, Shaun S. Sanders, Gonzalo L. Vilas, Pamela Arstikaitis, Jonathan Coutinho, Renaldo C. Drisdel, Alaa El Din El-Husseini, William N. Green, Luc Berthiaume, Michael R. Hayden
Journal: Circulation Research (2009)

ATP-binding cassette transporter (ABC)A1 lipidates apolipoprotein A-I both directly at the plasma membrane and also uses lipids from the late endosomal or lysosomal compartment in the internal lipidation of apolipoprotein A-I. However, how ABCA1 targeting to these specific membranes is regulated remains unknown. Palmitoylation is a dynamically regulated lipid modification that targets many proteins to specific membrane domains. We hypothesized that palmitoylation may also regulate ABCA1 transport and function. Indeed, ABCA1 is robustly palmitoylated at cysteines 3, -23, -1110, and -1111. Abrogation of palmitoylation of ABCA1 by mutation of the cysteines results in a reduction of ABCA1 localization at the plasma membranes and a reduction in the ability of ABCA1 to efflux lipids to apolipoprotein A-I. ABCA1 is palmitoylated by the palmitoyl transferase DHHC8, and increasing DHHC8 protein results in increased ABCA1-mediated lipid efflux. Thus, palmitoylation regulates ABCA1 localization at the plasma membrane, and regulates its lipid efflux ability.
Atypical Spitz tumours and sentinel lymph node biopsy: a systematic review
Authors: Aimilios Lallas, Athanassios Kyrgidis, Gerardo Ferrara, Harald Kittler, Zoe Apalla, Fabio Castagnetti, Caterina Longo, Elvira Moscarella, Simonetta Piana, Iris Zalaudek, Giuseppe Argenziano
Journal: The Lancet Oncology (2014)
Comparative genetic patterns of glioblastoma multiforme: Potential diagnostic tool for tumor classification
Authors: Rodney N. Wiltshire, B.K. Ahmed Rasheed, Henry S. Friedman, Allan H. Friedman, Sandra H. Bigner
Journal: Neuro-Oncology (2000)

Cytogenetic and molecular genetic studies of glioblastoma multiforme (GBM) have shown that the most frequent alterations are gains of chromosome 7, losses of 9p loci and chromosome 10, and gene amplification, primarily of the epidermal growth factor receptor (EGFR) gene. Although this profile is potentially useful in distinguishing GBM from other tumor types, the techniques used tend to be labor intensive, and some can detect only gains or losses of genetic loci. Comparative genomic hybridization (CGH) is a powerful technique capable of identifying both gains and losses of DNA sequences. The present study compares the CGH evaluation of 22 GBM with classic cytogenetics, loss of heterozygosity by allelotyping, and gene amplification by Southern blot analysis to determine the reliability of CGH in the genetic characterization of GBM. The CGH and karyotypic data were consistent in showing gain of chromosome 7 accompanied by a loss of chromosome 10 as the most frequent abnormality, followed by a loss of 9p in 17 of 22 GBM cases. Loss of heterozygosity of chromosomes 10 (19/22) and 9p (9/22) loci confirmed the underrepresentation by CGH. Genomic amplifications were observed by CGH in 5 of the 10 cases where gene amplification was detected by Southern blot analysis. The data show that CGH is equally reliable, compared with the more established genetic methods, for recognizing the prominent genetic alterations associated with GBM and support its use as a plausible adjunct to glioma classification.
Cell cycle-related kinase mediates viral-host signalling to promote hepatitis B virus-associated hepatocarcinogenesis
Authors: Zhuo Yu, Yue-Qiu Gao, Hai Feng, Ying-Ying Lee, May S Li, Yuan Tian, Minnie Y Y Go, Dae-Yeul Yu, Yue-Sun Cheung, Paul B S Lai, Jun Yu, Vincent W S Wong, Joseph J Y Sung, Henry L Y Chan, Alfred S L Cheng
Journal: Gut (2014)

Background Androgen receptor (AR) signalling contributes to male predominance in hepatocellular carcinoma (HCC), which is more pronounced in HBV-endemic areas. Cell cycle-related kinase (CCRK) is essential for AR-induced hepatocarcinogenesis but its molecular function in HBV-associated HCC remains obscure. Objective To determine the molecular function of CCRK in HBV-associated HCC. Design Transcriptional regulation was assessed by chromatin immunoprecipitation, promoter mutation and luciferase reporter assays. Hepatocellular proliferation and tumourigenesis were examined by colony formation, soft agar assays and using HBV X protein (HBx) transgenic mice with low-dose exposure to diethylnitrosamine. Protein expressions were examined in clinical samples and correlated with patient survival by log-rank Mantel–Cox test. Results Overexpression of CCRK, but not its kinase-defective mutant, activated β-catenin/T cell factor signalling through phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9, led to upregulation of AR transcriptional activity and, subsequently, expression of HBx. The viral transactivator in turn induced CCRK expression through enhanced AR signalling, thus forming a positive regulatory loop. RNA interference silencing of CCRK, which suppressed the CCRK/GSK-3β/β-catenin/AR regulatory loop, significantly suppressed HBx-induced hepatocellular proliferation (p=0.001) and transformation (p&lt;0.001) and remarkably reduced &gt;80% diethylnitrosamine-mediated hepatocarcinogenesis in HBx transgenic mice. Finally, patients with HBV-associated HCC with concordant overexpression of CCRK, GSK-3β phosphorylation at Ser9, active dephosphorylated β-catenin and AR phosphorylation at Ser81 had poorer overall (HR=31.26, p&lt;0.0001) and disease-free (HR=3.60, p&lt;0.01) survival rates. Conclusions Our findings highlight the critical role of CCRK in a self-reinforcing circuitry that regulates HBV-associated hepatocarcinogenesis. Further characterisation of this intricate viral-host signalling may provide new prognostic biomarkers and therapeutic targets for HCC treatment.
Differential Regulation of B Cell Development, Activation, and Death by the Src Homology 2 Domain–Containing 5′ Inositol Phosphatase (Ship)
Authors: Anne Brauweiler, Idan Tamir, Joseph Dal Porto, Robert J. Benschop, Cheryl D. Helgason, R. Keith Humphries, John H. Freed, John C. Cambier
Journal: The Journal of Experimental Medicine (2000)

Although the Src homology 2 domain–containing 5′ inositol phosphatase (SHIP) is a well-known mediator of inhibitory signals after B cell antigen receptor (BCR) coaggregation with the low affinity Fc receptor, it is not known whether SHIP functions to inhibit signals after stimulation through the BCR alone. Here, we show using gene-ablated mice that SHIP is a crucial regulator of BCR-mediated signaling, B cell activation, and B cell development. We demonstrate a critical role for SHIP in termination of phosphatidylinositol 3,4,5-triphosphate (PI[3,4,5]P3) signals that follow BCR aggregation. Consistent with enhanced PI(3,4,5)P3 signaling, we find that splenic B cells from SHIP-deficient mice display enhanced sensitivity to BCR-mediated induction of the activation markers CD86 and CD69. We further demonstrate that SHIP regulates the rate of B cell development in the bone marrow and spleen, as B cell precursors from SHIP-deficient mice progress more rapidly through the immature and transitional developmental stages. Finally, we observe that SHIP-deficient B cells have increased resistance to BCR-mediated cell death. These results demonstrate a central role for SHIP in regulation of BCR signaling and B cell biology, from signal driven development in the bone marrow and spleen, to activation and death in the periphery.
Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer
Authors: Chang-Shuo Huang, Shye-Jye Tang, Ling-Yen Chung, Cheng-Ping Yu, Jar-Yi Ho, Tai-Lung Cha, Chii-Cheng Hsieh, Hsiao-Hsien Wang, Guang-Huan Sun, Kuang-Hui Sun
Journal: Journal of the American Society of Nephrology (2014)

Galectin-1, a β-galactoside–binding lectin, is involved in many physiologic and pathologic processes, including cell adhesion, differentiation, angiogenesis, and tumor progression. However, the role of galectin-1 in kidney cancer remains elusive. This study evaluated the role of galectin-1 in the progression and clinical prognosis of renal cell carcinoma. We found significant overexpression of galectin-1 in both kidney cancer cell lines and metastatic tissue specimens from patients with renal cell carcinoma. Knockdown of galectin-1 gene expression in renal cancer cell lines reduced cell invasion, clonogenic ability, and epithelial-mesenchymal transition in vitro; reduced tumor outgrowth in vivo; and inhibited the angiogenesis-inducing activity of these cells in vitro and in vivo. Galectin-1 knockdown decreased CXCR4 expression levels in kidney cancer cells, and restoration of CXCR4 expression in galectin-1–silenced cells rescued cell motility and clonogenic ability. Additional studies suggested that galectin-1 induced CXCR4 expression through activation of nuclear factor-κB (NF-κB). Analysis of patient specimens confirmed the clinical significance and positive correlation between galectin-1 and CXCR4 expression levels and revealed concomitant overexpression of galectin-1 and CXCR4 associated adversely with overall and disease-free survival. Our findings suggest that galectin-1 promotes tumor progression through upregulation of CXCR4 via NF-κB. The coordinated upregulation of galectin-1 and CXCR4 may be a novel prognostic factor for survival in patients with renal cell carcinoma and the galectin-1-CXCR4 axis may serve as a therapeutic target in this disease.
Laboratory diagnosis of hypersensitivity to<i> Anisakis simplex</i>: a review
Authors: I. Moneo, G. Curiel, L. Fernández de Corres, M. García, M. D. Del Pozo
Journal: Allergy (2000)

Patients suffering anaphylactic reactions after parasitized fish consumption have been reported in Spain in recent years. This reaction is different from the well‐known acute or chronic anisakiasis and causes intolerance to parasitized fish ingestion, even after appropriate cooking. High specific IgE values are usually found in these subjects. IgE immunoblotting is now needed to confirm the presence of specific IgE directed to several parasite antigens in order to exclude cross‐reactions. Positive specific IgG4 by immunoblotting was found in 60% of the patients, as well as in patients with anisakiasis, and probably reflected recent contact with the parasite proteins. The most specific response of IgE antibodies was directed to low‐molecular‐mass antigens of the parasite. Therefore, recombinant or purified antigens for in vivo and in vitro use will in future overcome some of the problems found in the diagnosis of sensitized patients.
Letter Regarding Article by Rotmans et al, “In Vivo Cell Seeding With Anti-CD34 Antibodies Successfully Accelerates Endothelialization but Stimulates Intimal Hyperplasia in Porcine Arteriovenous Expanded Polytetrafluoroethylene Grafts”
Authors: Brendan Doyle, Noel Caplice
Journal: Circulation (2005)
Non–Small-Cell Lung Cancer Vaccine Therapy: A Concise Review
Authors: Deirdre O'Mahony, Shivaani Kummar, Martin E. Gutierrez
Journal: Journal of Clinical Oncology (2005)

Lung cancer is the leading cause of cancer deaths in the United States and throughout the world; globally, there are more than 1.1 million deaths each year. Treatment modalities currently employed are significantly limited; 50% of patients experience disease recurrence after surgery, and less than a quarter of patients respond to systemic chemotherapy. These statistics have fueled the search for a safer, more effective treatment modality. Despite significant advances in our understanding of the molecular basis of cancer immunology, many obstacles remain. However, encouraging clinical results in patients immunized with autologous tumor cell vaccines expressing granulocyte macrophage colony-stimulating factor strongly advocate further investigation of immunotherapy in non-small-cell lung cancer (NSCLC). Further studies are needed to demonstrate whether these novel therapies can potentially complement or even replace current therapeutic approaches. We present a review of the various vaccine-based strategies employed to target and treat NSCLC.
Islamic Medical Association
Authors: Jane Cassidy
Journal: BMJ (2011)

The spokesman of the UK Islamic Medical Association, Abdel Majid Katme, admits that it’s a very small organisation with a big voice. The media attention given to his opinions is disproportionate to the size of the association, which no longer has a membership.

Its role now is as a health and educational lobby group and to voice Islamic views on medical ethics, says Dr Katme. This includes campaigning with other religious faiths, such as the Roman Catholic church, on common ethical concerns, including abortion.

Dr Katme would like to see an Islamic hospital in Britain where Muslims could be treated without worrying about matters such as being examined by a doctor of the opposite sex. Such anxieties keep Muslims at home when they might be in need of urgent medical attention, says the retired psychiatrist, who lives in London. …
STUDIES ON THE SITE OF THE FEEDBACK CONTROL OF CHOLESTEROL SYNTHESIS*†
Authors: Marvin D. Siperstein, M. Joanne Guest
Journal: Journal of Clinical Investigation (1960)

Despite wide variations in dietary cholesterol, most animals are capable of maintaining the cho- lesterol of their plasma at relatively constant levels.Insight into the means by which this homeo- statis of plasma cholesterol is accomplished was first provided when Gould and associates (3-5), Tom- kins, Sheppard and Chaikoff (6) and Frantz, Schneider and Hinkelman (7) independently dem- onstrated that cholesterol synthesis in the liver varies inversely with the level of dietary choles- terol.Since all endogenous plasma cholesterol probably originates in the liver (8-10), it is likely that the constancy of plasma cholesterol is the result of this reciprocal relationship between dietary cholesterol and hepatic cholesterogenesis.The mechanism by which exogenous choles- terol is able to suppress cholesterol synthesis in the liver is not as yet understood.Previous stud- ies of this problem have been carried out by Gould and Popja'k (11) who presented preliminary evi- dence indicating that the conversion of mevalonic acid to cholesterol in liver homogenates is not im- paired by cholesterol feeding.Similarly, since completion of our study, Bucher, McGarrahan, Gould and Loud (12, 13), employing an approach similar to that used here, have clearly demon- strated that in homogenates the reactions in- volved in the conversion of mevalonic acid to cholesterol are not greatly influenced by dietary cholesterol.These experiments (11-13), as well as the present investigation, provide evidence that the site of control of cholesterol synthesis is located proximal to the utilization of mevalonic acid.The present report describes studies which