tbuckley/cabot-search huggingface dataset:
Extending Primary Care: Polyclinics, Resource Centres, Hospitals-at-Home
Authors: C. Van Weel
Journal: BMJ (1996)

Ed Pat Gordon, Janet Hadley Radcliffe, £16.50, pp 160 ISBN 1 85775 029 2

The development of primary care-led health care continues, building on the experience of the past decades. The initial development of primary care focused on the medical aspects and was at first confined to a few countries (Britain, Denmark, Canada, and the Netherlands). It resulted in academically based, specially trained general practitioners, though it is only fair to emphasise that Dutch general practice traditionally reached beyond the core of medical care facilities. I entered general practice in a “primary care” team whose members included …
An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis
Authors: C P Denton, M Engelhart, N Tvede, H Wilson, K Khan, X Shiwen, P E Carreira, F Diaz Gonzalez, C M Black, F H van den Hoogen
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Aim:</h3> The safety and potential efficacy of a chimaeric anti-tumour necrosis factor alpha monoclonal antibody (infliximab) were examined in diffuse cutaneous systemic sclerosis (dcSSc). <h3>Methods:</h3> A 26-week open-label pilot study in which 16 cases of dcSSc received five infusions of infliximab (5 mg/kg). Clinical assessment included skin sclerosis score, scleroderma health assessment questionnaire, self-reported functional score and physician global visual analogue scale. Collagen turnover, skin biopsy analysis and full safety evaluation were performed. <h3>Results:</h3> There was no significant change in skin score at 26 weeks but a trend for lower modified Rodnan skin score at 22 weeks (OR 17, 95% CI 6 to 46) compared with peak value (OR 29, 95% CI 11 to 44; p = 0.10). Serum aminoterminal propeptide of type III collagen level was significantly lower at week 26 compared with baseline (p = 0.03). Secretion of type I collagen by dermal fibroblasts was reduced at 26 weeks compared with baseline (p = 0.02). There were no deaths during the study and no suspected unexpected serious adverse reactions. 21 serious adverse events (AE) occurred in seven subjects, mostly attributable to dcSSc. 127 distinct AE occurred in 16 subjects. Of these, 19 AE (15%) were probably or definitely related to infliximab treatment. Eight (50%) patients prematurely discontinued infliximab. Anti-infliximab antibodies developed during the study in five subjects and were significantly associated with suspected infusion reactions (p = 0.025). <h3>Conclusion:</h3> In dcSSc infliximab did not show clear benefit at 26 weeks but was associated with clinical stabilisation and a fall in two laboratory markers of collagen synthesis. The frequency of suspected infusion reactions may warrant additional immunosuppression in any future studies in systemic sclerosis.
Pseudofolliculitis cutis: a vexing disorder of hair growth
Authors: T.J. Jasterzbski, R.A. Schwartz
Journal: British Journal of Dermatology (2014)

Pseudofolliculitis cutis (PFC) is a troublesome and potentially disfiguring cutaneous disorder characterized by a chronic inflammatory response to ingrown hair. Despite a simple precipitating stimulus, ingrown hair, PFC has a relatively complex aetiology that can involve grooming practices, hair type, genetic predisposition and medication history. Curly hair and a single-nucleotide substitution in the gene encoding keratin 75 may act synergistically to increase the risk for developing this condition. PFC is most common in men of sub-Saharan African lineage, but can occur in men and women of many different ethnicities, particularly in body areas where hair is coarse, abundant and subject to traumatic removal. Treatment options for PFC can be divided into three main categories: modifying hair removal practices, managing symptoms with medication, and long-term hair removal with laser therapy. Laser hair removal is safe and effective in most skin types and has become increasingly popular among dermatologists in the treatment of PFC. However, it is imperative that the laser system and parameters are specifically matched to the patient's skin type.
Invasive infection with Trichosporon inkin in 2 siblings with chronic granulomatous disease
Authors: Sarah M. Wynne, Kyung J. Kwon-Chung, Yvonne R. Shea, Armando C. Filie, Ashok Varma, Petrizia Lupo, Steven M. Holland
Journal: Journal of Allergy and Clinical Immunology (2004)
Peroxisome Proliferator-Activated Receptor γ Inhibition Prevents Adhesion to the Extracellular Matrix and Induces Anoikis in Hepatocellular Carcinoma Cells
Authors: Katherine L. Schaefer, Koichiro Wada, Hirokazu Takahashi, Nobuyuki Matsuhashi, Shin Ohnishi, M. Michael Wolfe, Jerrold R. Turner, Atsushi Nakajima, Steven C. Borkan, Lawrence J. Saubermann
Journal: Cancer Research (2005)

Abstract Activation of the nuclear transcription factor peroxisome proliferator-activated receptor γ (PPARγ) inhibits growth and survival of hepatocellular carcinoma (HCC) cell lines. To further investigate the function of PPARγ in HCC, PPARγ expression patterns in primary tumors were examined, and the responses of two HCC cell lines to PPARγ activation and inhibition were compared. PPARγ expression was increased in HCC and benign-appearing peritumoral hepatocytes compared with remote benign hepatocytes. Both compound PPARγ inhibitors and PPARγ small interfering RNAs prevented HCC cell lines from adhering to the extracellular matrix. Loss of adhesion was followed by caspase-dependent apoptosis (anoikis). PPARγ inhibitors had no effect on initial β1 integrin-mediated adhesion, or on total focal adhesion kinase levels but did reduce focal adhesion kinase phosphorylation. The PPARγ inhibitor T0070907 was significantly more efficient at causing cancer cell death than the activators troglitazone and rosiglitazone. T0070907 caused cell death by reducing adhesion and inducing anoikis, whereas the activators had no direct effect on adhesion and caused cell death at much higher concentrations. In conclusion, PPARγ overexpression is present in HCC. Inhibition of PPARγ function causes HCC cell death by preventing adhesion and inducing anoikis-mediated apoptosis. PPARγ inhibitors represent a potential novel treatment approach to HCC.
Analgesic effect of breast feeding in term neonates: randomised controlled trial
Authors: R. Carbajal
Journal: BMJ (2003)

Objectives: To investigate whether breast feeding is effective for pain relief during venepuncture in term neonates and compare any effect with that of oral glucose combined with a pacifier. Design: Randomised controlled trial. Participants: 180 term newborn infants undergoing venepuncture; 45 in each group. Interventions: During venepuncture infants were either breast fed (group 1), held in their mother's arms without breast feeding (group 2), given 1 ml of sterile water as placebo (group 3), or given 1 ml of 30% glucose followed by pacifier (group 4). Video recordings of the procedure were assessed by two observers blinded to the purpose of the study. Main outcome measures: Pain related behaviours evaluated with two acute pain rating scales: the Douleur Aiguë Nouveau-né scale (range 0 to 10) and the premature infant pain profile scale (range 0 to 18). Results: Median pain scores (interquartile range) for breast feeding, held in mother's arms, placebo, and 30% glucose plus pacifier groups were 1 (0–3), 10 (8.5-10), 10 (7.5-10), and 3 (0–5) with the Douleur Aiguë Nouveau-né scale and 4.5 (2.25-8), 13 (10.5-15), 12 (9–13), and 4 (1–6) with the premature infant pain profile scale. Analysis of variance showed significantly different median pain scores (P<0.0001) among the groups. There were significant reductions in both scores for the breast feeding and glucose plus pacifier groups compared with the other two groups (P<0.0001, two tailed Mann-Whitney U tests between groups). The difference in Douleur Aiguë Nouveau-né scores between breast feeding and glucose plus pacifier groups was not significant (P=0.16). Conclusions: Breast feeding effectively reduces response to pain during minor invasive procedure in term neonates. #### What is already known on this topic What is already known on this topic Current pharmacological treatments are not appropriate for pain relief during minor procedures like venepuncture or heel prick in newborn infants Oral sweet solutions, non-nutritive sucking, and skin to skin contact reduce procedural pain in newborn infants #### What this study adds What this study adds Breast feeding during a painful procedure effectively reduces the response to pain in newborn infants The analgesic properties of breast feeding are at least as potent as the combination of sweet solutions and a pacifier
Histamine H4 receptor knockout mice display reduced inflammation in a chronic model of atopic dermatitis
Authors: K. Rossbach, K. Schaper, Ch. Kloth, R. Gutzmer, T. Werfel, M. Kietzmann, W. Bäumer
Journal: Allergy (2015)

The histamine H4 receptor (H4R) was brought into focus as a new therapeutic target for the treatment of allergic disorders such as atopic dermatitis (AD). H4R antagonists have already been tested in several animal models of AD, but these studies have yielded conflicting results.The development of ovalbumin-induced AD-like skin lesions was analysed in H4R(-/-) mice and in H4R antagonist (JNJ28307474)-treated mice.H4R(-/-) mice showed a clear amelioration of the skin lesions, with a diminished influx of inflammatory cells and a reduced epidermal hyperproliferation at lesional skin sites. H4R(-/-) mice had a reduced amount of ovalbumin-specific IgE, a reduced number of splenocytes and lymph node cells with a decreased number of CD4+ T cells. The H4R modulated the cytokine secretion of CD4+ T cells and splenocytes and altered the cellular profile in the lymph nodes. The anti-inflammatory effect could only partially be mimicked by JNJ28307474 and only when the H4R antagonist was given during sensitization and challenge and not when JNJ28307474 was only given during the provocation phase of the allergic reaction.The H4R modulates inflammation in a chronic allergic dermatitis setting. However, results of this study indicate that it is necessary to block the H4R during ontogeny and development of the allergic inflammation.
Plasma Cell Ontogeny Defined by Quantitative Changes in Blimp-1 Expression
Authors: Axel Kallies, Jhagvaral Hasbold, David M. Tarlinton, Wendy Dietrich, Lynn M. Corcoran, Philip D. Hodgkin, Stephen L. Nutt
Journal: The Journal of Experimental Medicine (2004)

Plasma cells comprise a population of terminally differentiated B cells that are dependent on the transcriptional regulator B lymphocyte–induced maturation protein 1 (Blimp-1) for their development. We have introduced a gfp reporter into the Blimp-1 locus and shown that heterozygous mice express the green fluorescent protein in all antibody-secreting cells (ASCs) in vivo and in vitro. In vitro, these cells display considerable heterogeneity in surface phenotype, immunoglobulin secretion rate, and Blimp-1 expression levels. Importantly, analysis of in vivo ASCs induced by immunization reveals a developmental pathway in which increasing levels of Blimp-1 expression define developmental stages of plasma cell differentiation that have many phenotypic and molecular correlates. Thus, maturation from transient plasmablast to long-lived ASCs in bone marrow is predicated on quantitative increases in Blimp-1 expression.
Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation
Authors: Ammar H Hawasli, David R Benavides, Chan Nguyen, Janice W Kansy, Kanehiro Hayashi, Pierre Chambon, Paul Greengard, Craig M Powell, Donald C Cooper, James A Bibb
Journal: Nature Neuroscience (2007)
Artificial Organ Society
Authors: D. Kerr
Journal: BMJ (1964)

BRmTIsH 1513individual case is unimportant, however bad; the principle is clear.If the disciplinary procedure of the N.H.S. is to include the laying down of what is "good " or " bad " doctoring then I, for one.will require to see in the terms of service some pretty exhaustive and stringent definitions, and it may be that we shall have to abandon our present easy-going informal procedure that Dr. Dain spent so many years building up.-I am, etc.,
Protein Kinase A Activation Confers Resistance to Trastuzumab in Human Breast Cancer Cell Lines
Authors: Long Gu, Sean K. Lau, Sofia Loera, George Somlo, Susan E. Kane
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Trastuzumab is a monoclonal antibody targeted to the Her2 receptor and approved for treatment of Her2-positive breast cancer. Among patients who initially respond to trastuzumab therapy, resistance typically arises within 1 year. BT/HerR cells are trastuzumab-resistant variants of Her2-positive BT474 breast cancer cells. The salient feature of BT/HerR cells is failure to downregulate phosphoinositide 3-kinase/Akt signaling on trastuzumab binding. The current work addresses the mechanism of sustained signaling in BT/HerR cells, focusing on the protein kinase A (PKA) pathway. Experimental Design: We performed microarray analysis on BT/HerR and BT474 cell lines to identify genes that were upregulated or downregulated in trastuzumab-resistant cells. Specific genes in the PKA pathway were quantified using reverse transcription-PCR and Western hybridization. Small interfering RNA transfection was used to determine the effects of gene knockdown on cellular response to trastuzumab. Electrophoretic mobility shift assays were used to measure cyclic AMP–responsive element binding activity under defined conditions. Immunohistochemistry was used to analyze protein expression in clinical samples. Results: BT/HerR cells had elevated PKA signaling activity and several genes in the PKA regulatory network had altered expression in these cells. Downregulation of one such gene, the PKA-RIIα regulatory subunit, conferred partial trastuzumab resistance in Her2-positive BT474 and SK-Br-3 cell lines. Forskolin activation of PKA also produced significant protection against trastuzumab-mediated Akt dephosphorylation. In patient samples, PKA signaling appeared to be enhanced in residual disease remaining after trastuzumab-containing neoadjuvant therapy. Conclusions: Activation of PKA signaling may be one mechanism contributing to trastuzumab resistance in Her2-positive breast cancer. We propose a molecular model by which PKA confers its effects. (Clin Cancer Res 2009;15(23):7196–206)
A vascular endothelial growth factor deficiency characterises scleroderma lung disease
Authors: Maria De Santis, Silvia Laura Bosello, Ettore Capoluongo, Rosanna Inzitari, Giusy Peluso, Paola Lulli, Gaetano Zizzo, Mario Bocci, Barbara Tolusso, Cecilia Zuppi, Massimo Castagnola, Gianfranco Ferraccioli
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> Vascular endothelial growth factor (VEGF) is thought to play an important role in systemic sclerosis (SSc) pathogenesis. It was found to be upregulated in the serum and in the affected skin of scleroderma patients. However, its involvement in scleroderma lung disease is not clear. This study aimed to evaluate VEGF concentration in the bronchoalveolar lavage fluid (BALF) of scleroderma patients with interstitial lung disease, to correlate the cytokine levels in plasma and in the lung with pulmonary functional, radiological and cellular parameters, and with the progression of lung disease. <h3>Methods</h3> BALF and plasma VEGF concentrations were analysed by ELISA in 55 SSc patients with lung disease and 17 controls. Cytokine real-time PCR messenger RNA expression in alveolar macrophages was assessed. Lung involvement progression was evaluated after a 1-year follow-up. <h3>Results</h3> VEGF was found to be significantly lower in the BALF of scleroderma patients compared with controls. The lowest concentrations were observed in SSc patients with alveolitis. A decreased VEGF expression in alveolar macrophages was found in SSc patients with alveolitis. VEGF concentration in BALF correlated inversely with the ground glass score on high-resolution CT and with BALF neutrophil cell count. Moreover, SSc patients with a lower VEGF concentration showed a worsening in the interstitial score at follow-up. <h3>Conclusions</h3> Scleroderma interstitial lung disease is characterised by a VEGF deficiency. Lower concentrations were found in patients with progression of lung disease.
WT1 Activates a Glomerular-Specific Enhancer Identified from the Human Nephrin Gene
Authors: Gordon Guo, Debra J. Morrison, Jonathan D. Licht, Susan E. Quaggin
Journal: Journal of the American Society of Nephrology (2004)

The glomerular filtration barrier separates the blood from the urinary space. Nephrin is a transmembrane protein that belongs to the immunoglobulin superfamily and is localized to the slit diaphragms that are a critical component of this filtration barrier. Mutations in the nephrin gene (NPHS1) lead to congenital Finnish nephropathy, whereas alterations in the level of nephrin expression have been identified in a wide range of acquired glomerular diseases. A 186-bp fragment from the human NPHS1 promoter is capable of directing podocyte-specific expression of a beta-galactosidase transgene when placed in front of a heterologous minimal promoter in transgenic mice. The Wilms tumor suppressor gene (WT1) is a zinc-finger-containing transcription factor that is coexpressed with NPHS1 in differentiated podocytes; gel shift binding assays demonstrate that a recombinant WT1 protein can bind and activate the 186-bp NPHS1 fragment in a sequence-specific manner. Taken together, these results suggest that WT1 may be required for regulation of the NPHS1 gene in vivo.
Risk factors for severe complications of the novel influenza A (H1N1): analysis of patients hospitalized in Italy
Authors: M. Bassetti, A. Parisini, A. Calzi, F.M. Bobbio Pallavicini, G. Cassola, S. Artioli, M. Anselmo, G. Pagano, G. Rezza, C. Viscoli
Journal: Clinical Microbiology and Infection (2010)
Effects of Reconstituted High-Density Lipoprotein Infusions on Coronary Atherosclerosis&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Jean-Claude Tardif, Jean Grégoire, Philippe L L'Allier, Reda Ibrahim, Jacques Lespérance, Therese M Heinonen, Simon Kouz, Colin Berry, Russell Basser, Marc-André Lavoie, Marie-Claude Guertin, Josep Rodés-Cabau
Journal: JAMA (2007)

High-density lipoprotein (HDL) cholesterol is an inverse predictor of coronary atherosclerotic disease. Preliminary data have suggested that HDL infusions can induce atherosclerosis regression.To investigate the effects of reconstituted HDL on plaque burden as assessed by intravascular ultrasound (IVUS).A randomized placebo-controlled trial was conducted at 17 centers in Canada. Intravascular ultrasound was performed to assess coronary atheroma at baseline and 2 to 3 weeks after the last study infusion.Between July 2005 and October 2006, 183 patients had a baseline IVUS examination and of those, 145 had evaluable serial IVUS examinations after 6 weeks.Sixty patients were randomly assigned to receive 4 weekly infusions of placebo (saline), 111 to receive 40 mg/kg of reconstituted HDL (CSL-111); and 12 to receive 80 mg/kg of CSL-111.The primary efficacy parameter was the percentage change in atheroma volume. Nominal changes in plaque volume and plaque characterization index on IVUS and coronary score on quantitative coronary angiography were also prespecified end points.The higher-dosage CSL-111 treatment group was discontinued early because of liver function test abnormalities. The percentage change in atheroma volume was -3.4% with CSL-111 and -1.6% for placebo (P = .48 between groups, P<.001 vs baseline for CSL-111). The nominal change in plaque volume was -5.3 mm3 with CSL-111 and -2.3 mm3 with placebo (P = .39 between groups, P<.001 vs baseline for CSL-111). The mean changes in plaque characterization index on IVUS (-0.0097 for CSL-111 and 0.0128 with placebo) and mean changes in coronary score (-0.039 mm for CSL-111 and -0.071 mm with placebo) on quantitative coronary angiography were significantly different between groups (P = .01 and P =.03, respectively). Administration of CSL-111 40 mg/kg was associated with mild, self-limiting transaminase elevation but was clinically well tolerated.Short-term infusions of reconstituted HDL resulted in no significant reductions in percentage change in atheroma volume or nominal change in plaque volume compared with placebo but did result in statistically significant improvement in the plaque characterization index and coronary score on quantitative coronary angiography. Elevation of HDL remains a valid target in vascular disease and further studies of HDL infusions, including trials with clinical end points, appear warranted.clinicaltrials.gov Identifier: NCT00225719
Immortalization of Human Bronchial Epithelial Cells in the Absence of Viral Oncoproteins
Authors: Ruben D. Ramirez, Shelley Sheridan, Luc Girard, Mitsuo Sato, Young Kim, Jon Pollack, Michael Peyton, Ying Zou, Jonathan M. Kurie, J. Michael DiMaio, Sara Milchgrub, Alice L. Smith, Rhonda F. Souza, Laura Gilbey, Xi Zhang, Kenia Gandia, Melville B. Vaughan, Woodring E. Wright, Adi F. Gazdar, Jerry W. Shay, John D. Minna
Journal: Cancer Research (2004)

By expressing two genes (hTERT and Cdk4), we have developed a method to reproducibly generate continuously replicating human bronchial epithelial cell (HBEC) lines that provide a novel resource to study the molecular pathogenesis of lung cancer and the differentiation of bronchial epithelial cells. Twelve human bronchial epithelial biopsy specimens obtained from persons with and without lung cancer were placed into short-term culture and serially transfected with retroviral constructs containing cyclin-dependent kinase (Cdk) 4 and human telomerase reverse transcriptase (hTERT), resulting in continuously growing cultures. The order of introduction of Cdk4 and hTERT did not appear to be important; however, transfection of either gene alone did not result in immortalization. Although they could be cloned, the immortalized bronchial cells did not form colonies in soft agar or tumors in nude mice. The immortalized HBECs have epithelial morphology; express epithelial markers cytokeratins 7, 14, 17, and 19, the stem cell marker p63, and high levels of p16(INK4a); and have an intact p53 checkpoint pathway. Cytogenetic analysis and array comparative genomic hybridization profiling show immortalized HBECs to have duplication of parts of chromosomes 5 and 20. Microarray gene expression profiling demonstrates that the Cdk4/hTERT-immortalized bronchial cell lines clustered together and with nonimmortalized bronchial cells, distinct from lung cancer cell lines. We also immortalized several parental cultures with viral oncoproteins human papilloma virus type 16 E6/E7 with and without hTERT, and these cells exhibited loss of the p53 checkpoint and significantly different gene expression profiles compared with Cdk4/hTERT-immortalized HBECs. These HBEC lines are a valuable new tool for studying of the pathogenesis of lung cancer.