tbuckley/cabot-search huggingface dataset:
A Glimpse of Various Pathogenetic Mechanisms of Diabetic Nephropathy
Authors: Yashpal S. Kanwar, Lin Sun, Ping Xie, Fu-you Liu, Sheldon Chen
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Diabetic nephropathy is a well-known complication of diabetes and is a leading cause of chronic renal failure in the Western world. It is characterized by the accumulation of extracellular matrix in the glomerular and tubulointerstitial compartments and by the thickening and hyalinization of intrarenal vasculature. The various cellular events and signaling pathways activated during diabetic nephropathy may be similar in different cell types. Such cellular events include excessive channeling of glucose intermediaries into various metabolic pathways with generation of advanced glycation products, activation of protein kinase C, increased expression of transforming growth factor β and GTP-binding proteins, and generation of reactive oxygen species. In addition to these metabolic and biochemical derangements, changes in the intraglomerular hemodynamics, modulated in part by local activation of the renin-angiotensin system, compound the hyperglycemia-induced injury. Events involving various intersecting pathways occur in most cell types of the kidney.
Therapeutic Efficacy of Antigen-Specific Vaccination and Toll-Like Receptor Stimulation against Established Transplanted and Autochthonous Melanoma in Mice
Authors: Damia Tormo, Aleix Ferrer, Pilar Bosch, Evelyn Gaffal, Etiena Basner-Tschakarjan, Jörg Wenzel, Thomas Tüting
Journal: Cancer Research (2006)

Abstract Malignant melanoma is an attractive model disease for the development of antigen-specific immunotherapy because many antigens recognized by tumor-specific T cells have been identified. In C57BL/6 mice, genetic immunization with recombinant adenovirus encoding xenogeneic human tyrosinase-related protein 2 (Ad-hTRP2) induces protective but not therapeutic cellular immunity against growth of transplanted B16 melanoma cells. Here, we additionally applied CpG DNA and synthetic double-stranded RNA, which activate the innate immune system via Toll-like receptors (TLR). Both adenoviral vaccination and peritumoral injections of TLR ligands were required for rejection of established B16 melanoma in the skin. To more closely mimic the clinical situation in patients with melanoma, we evaluated this combined immunotherapeutic strategy in genetically modified mice, which overexpress hepatocyte growth factor (HGF) and carry an oncogenic mutation in the cyclin-dependent kinase 4 (CDK4)R24C. HGF × CDK4R24C mice rapidly develop multiple invasive melanomas in the skin following neonatal carcinogen treatment, which spontaneously metastasize to lymph nodes and lungs. Vaccination with Ad-hTRP2 followed by injections of TLR ligands resulted in delayed growth of autochthonous primary melanomas in the skin and reduction in the number of spontaneous lung metastases but did not induce tumor regression. Carcinogen-treated HGF × CDK4R24C mice bearing multiple autochthonous melanomas did not reject transplanted B16 melanoma despite treatment with Ad-hTRP2 and TLR ligands, suggesting the development of tumor immunotolerance. Further investigations in our novel genetic melanoma model may help to better understand the role of the immune system in the pathogenesis and treatment of this life-threatening disease. (Cancer Res 2006; 66(10): 5427-35)
Control of Hand Prostheses Using Peripheral Information
Authors: Silvestro Micera, Jacopo Carpaneto, Stanisa Raspopovic
Journal: IEEE Reviews in Biomedical Engineering (2010)

Several efforts have been carried out to enhance dexterous hand prosthesis control by impaired individuals. Choosing which voluntary signal to use for control purposes is a critical element to achieve this goal. This review presents and discusses the recent results achieved by using electromyographic signals, recorded either with surface (sEMG) or intramuscular (iEMG) electrodes, and electroneurographic (ENG) signals. The potential benefits and shortcomings of the different approaches are described with a particular attention to the definition of all the steps required to achieve an effective hand prosthesis control in the different cases. Finally, a possible roadmap in the field is also presented.
Endobronchial closure of central bronchial fistula with septal occluder devices
Authors: Satya Prakash Rai, Vimal Someshwar, R. Ravikumar
Journal: European Respiratory Journal (2013)

Introduction: We describe a novel method of Bronchopulmonary fistula (BPF) closure using occluder devices (PDA, VSD and ASD closure device) in three patients under bronchoscopy and fluoroscopy control.

Case1. A persistent bronchopleurocutaneous fistula was successfully closed with a PDA Amplatzer device.

Case 2. A persistent broncho-esophageal fistula was successfully closed by an amplatzer VSD closure device.

Case 3 . A postoperative persistent BPF in cirrhotic was closed by a Lifetech ASD septal closure device delivered through bronchoscope.

![Figure][1] 



Figure 1 . ASD septal occluder device after deployment occluding RUL

Conclusion: Endobronchial closure of bronchial fistulas using the occluder device (PDA, VSD and ASD closure device) is a safe, minimally invasive and effective modality for treatment of large central bronchial fistulas.

References 

1. Golbin JM,Prakash UB. Closure of a bronchopleural fistula using an amplatzer septal occluder device. Chest 2006;129:479-81

2. Fruchter O, Kramer MR et al. Endobronchial closure of bronchopleural fistulae using amplatzer devices: our experience and literature review.Chest 2011; 139: 682-7

3. Kramer MR, Peled N et al. Use of Amplatzer device for endobronchial closure of bronchopleural fistulas. Chest 2008; 133:1481-4.

 [1]: pending:yes
CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE
Authors: G. M. Shearer, G. Cudkowicz, Mary St. James Connell, R. L. Priore
Journal: The Journal of Experimental Medicine (1968)

Spleen cell suspensions of unprimed donor mice containing precursors of immunocytes have been transplanted into X-irradiated recipient mice. In the presence of antigen (sheep erythrocytes) these precursors, called antigen-sensitive units, gave rise to progeny cells secreting specific antibody. We studied quantitatively the production of cells releasing IgM hemolysins (direct plaque-forming cells), IgG hemolysins (indirect plaque-forming cells), and hemagglutinins (cluster-forming cells). We found that each of these immunocyte populations was distinct, i.e., that cells releasing agglutinins did not, as a rule, release hemolysins, and vice versa. We also found that cell populations secreting IgM hemolysins did not shift, under certain experimental conditions, to the production of IgG hemolysins during the primary immune response. By transplanting graded numbers of spleen cells, we succeeded in limiting to one or a few the number of antigen-sensitive units that reached the recipient spleen. We estimated thereby the frequency of antigen-sensitive units in donor cell suspensions and tested their potential for production of immunocytes of more than one type. Our results indicated that antigen-sensitive units were unipotent for they displayed in the spleens of unprimed donors the same restrictions of function and heterogeneity (antibody-specificity differentiation, antibody-class differentiation) found among antibody-forming cells. Furthermore, antigen-sensitive precursors for direct plaque-forming cells, indirect plaque-forming cells, and cluster-forming cells were detected in the spleens of unprimed mice in different frequencies, i.e., 1 in ∼ 106, 1 in ∼ 7 x 106, and 1 in ∼ 19 x 106 spleen cells, respectively. We concluded that relatively advanced differentiation of potentially competent cells occurs before sheep erythrocyte administration. The relevance of this finding for the broad spectrum of immunologic reactivities and for the heterogeneity of antibody responses to given antigens was discussed.
Guidelines for topical PUVA: a report of a workshop of the British Photodermatology Group
Authors: S.M. Halpern, A.V. Anstey, R.S. Dawe, B.L. Diffey, P.M. Farr, J. Ferguson, J.L.M. Hawk, S. Ibbotson, J.M. Mcgregor, G.M. Murphy, S.E. Thomas, L.E. Rhodes
Journal: British Journal of Dermatology (2000)

Psoralen photochemotherapy [psoralen ultraviolet A (PUVA)] plays an important part in dermatological therapeutics, being an effective and generally safe treatment for psoriasis and other dermatoses. In order to maintain optimal efficacy and safety, guidelines concerning best practice should be available to operators and supervisors. The British Photodermatology Group (BPG) have previously published recommendations on PUVA, including UVA dosimetry and calibration, patient pretreatment assessment, indications and contraindications, and the management of adverse reactions.1 While most current knowledge relates to oral PUVA, the use of topical PUVA regimens is also popular and presents a number of questions peculiar to this modality, including the choice of psoralen, formulation, method of application, optimal timing of treatment, UVA regimens and relative benefits or risks as compared with oral PUVA. Bath PUVA, i.e. generalized immersion, is the most frequently used modality of topical treatment, practised by about 100 centres in the U.K., while other topical preparations tend to be used for localized diseases such as those affecting the hands and feet. This paper is the product of a recent workshop of the BPG and includes guidelines for bath, local immersion and other topical PUVA. These recommendations are based, where possible, on the results of controlled studies, or otherwise on the consensus view on current practice.
Global mRNA decay analysis at single nucleotide resolution reveals segmental and positional degradation patterns in a Gram-positive bacterium
Authors: Simen M Kristoffersen, Chad Haase, M Ryan Weil, Karla D Passalacqua, Faheem Niazi, Stephen K Hutchison, Brian Desany, Anne-Brit Kolstø, Nicolas J Tourasse, Timothy D Read, Ole Økstad
Journal: Genome biology (2012)

Recent years have shown a marked increase in the use of next-generation sequencing technologies for quantification of gene expression (RNA sequencing, RNA-Seq). The expression level of a gene is a function of both its rate of transcription and RNA decay, and the influence of mRNA decay rates on gene expression in genome-wide studies of Gram-positive bacteria is under-investigated. In this work, we employed RNA-Seq in a genome-wide determination of mRNA half-lives in the Gram-positive bacterium Bacillus cereus. By utilizing a newly developed normalization protocol, RNA-Seq was used successfully to determine global mRNA decay rates at the single nucleotide level. The analysis revealed positional degradation patterns, with mRNAs being degraded from both ends of the molecule, indicating that both 5' to 3' and 3' to 5' directions of RNA decay are present in B. cereus. Other operons showed segmental degradation patterns where specific ORFs within polycistrons were degraded at variable rates, underlining the importance of RNA processing in gene regulation. We determined the half-lives for more than 2,700 ORFs in B. cereus ATCC 10987, ranging from less than one minute to more than fifteen minutes, and showed that mRNA decay rate correlates globally with mRNA expression level, GC content, and functional class of the ORF. To our knowledge, this study presents the first global analysis of mRNA decay in a bacterium at single nucleotide resolution. We provide a proof of principle for using RNA-Seq in bacterial mRNA decay analysis, revealing RNA processing patterns at the single nucleotide level.
White paper whiteout
Authors: Mark Aitken
Journal: Journal of the Royal Society of Medicine (2010)

The recent flurry of white paper activity from the Department of Health1–3 looks like yet another attempt to invite us to milk those parts of the NHS sacred cow from which milk was never meant to flow.4 Isn't now the time to unite and synthesize the solution which generations of politicians have failed to deliver? A tough call, particularly when you realize that hospital consultants are not included in the Government's consultative process! It is difficult to know whether our exclusion is because of our previous avaricious expressions of self-interest which preceded the final NHS Act in 1948, or because the Government has understandably forgotten that doctors are supposed to be the champions of healthcare delivery. Either way, we need to get back into the driving seat and, without any preconditions, give this every ounce of energy that our brains can muster.
GW25-e4552 Expression of Connexin 43 in Non-culprit arteries and Role of Angiotensin II in Expression of Connexin 43
Authors: Wang Jian, Jing-Hua Liu, Shao-Ping Wang, Ming Zhang, Chang-Hua Wang, Ping Wang, Ze Zheng, Jian Wang
Journal: Journal of the American College of Cardiology (2014)
Increased Immunogenicity of Colon Cancer Cells by Selective Depletion of Cytochrome<i>c</i>
Authors: Elise Schmitt, Arnaud Parcellier, François Ghiringhelli, Noelia Casares, Sandeep Gurbuxani, Nathalie Droin, Ahmed Hamai, Marie Pequignot, Arlette Hammann, Monique Moutet, Annie Fromentin, Guido Kroemer, Eric Solary, Carmen Garrido
Journal: Cancer Research (2004)

Abstract We and others have previously reported in an in vivo rat colon cancer cell model that cell death precedes and is necessary for the development of a specific antitumoral immune response. To sensitize colon cancer cells to death, we depleted cytochrome c by stable transfection with an antisense construct. Cytochrome c depletion sensitizes human and rat colon cancer cells to a nonapoptotic, nonautophagic death induced by various stimuli. This increased sensitization to a necrosis-like cell death may be related to a decrease in cellular ATP levels and an increase in reactive oxygen species production caused by cytochrome c depletion. In vivo, depletion of cytochrome c decreases the tumorigenicity of colon cancer cells in syngeneic rats without influencing their growth in immune-deficient animals. Furthermore, decreased expression of cytochrome c in tumor cells facilitates in vivo “necrotic” cell death and the induction of a specific immune response. These results delineate a novel strategy to sensitize colon cancer cells to chemotherapy and to increase their immunogenicity in immuno-competent hosts.
The HCCR Oncoprotein as a Biomarker for Human Breast Cancer
Authors: Sang Seol Jung, Hyung Soon Park, Insong James Lee, Hong Namkoong, Seung Min Shin, Goang Won Cho, Seon-Ah Ha, Yong Gyu Park, Youn Soo Lee, Jesang Ko, Jin Woo Kim
Journal: Clinical Cancer Research (2005)

Abstract Purpose: HCCR oncoprotein is reported to be related to tumorigenesis, including breast cancer, functioning as a negative regulator of p53. Mice transgenic for HCCR developed breast cancers. The objective of this study was to validate the HCCR oncoprotein as a candidate biomarker for breast cancer. Experimental Design: HCCR expression in breast cancer cells was analyzed by quantitative PCR, ELISA, immunohistochemistry, Western blotting, fluorescence-activated cell sorting, and confocal microscopy. Epitope areas were determined using mass spectrometry through the analysis of time-dependent tryptic fragment patterns of HCCR. HCCR expression profiles in breast cancer patient sera were analyzed, and correlations with clinicopathologic data and carbohydrate antigen 15-3 (CA15-3) levels were determined. Results: HCCR was up-regulated in breast cancer cells and tissues. The epitope regions of HCCR recognized by monoclonal antibody (BCS-1) were HFWTPK and QQTDFLDIYHAFR. According to fluorescence-activated cell sorting and confocal microscopic analysis, BCS-1 was bound to HCCR antigen on the cell surface. Serum HCCR concentrations were measured using ELISA from 299 subjects, including 129 patients with breast cancer, 24 patients with benign breast disease, and 158 normal volunteers, and comparisons were made to CA15-3. Serologic studies revealed an 86.8% sensitivity for HCCR in breast cancer, which was higher than 21.0% for CA15-3. Eighty-six of 98 (87.8%) patients with breast cancers that were negative for CA15-3 were positive for HCCR-1. A positive response rate of 83.3% was identified even at early stages for pathologic factors in breast cancer. Conclusions: The HCCR assay has an advantage over CA15-3 in diagnosing breast cancer and detecting early stages of the disease.
The Expression of P53, &amp;Bgr;-Tubulin, Bcl-2 According to P16 Status in Advanced Oropharyngeal Cancer After Induction Chemotherapy Followed By Concurrent Chemoradiotherapy
Authors: S. Cho, H. Shim, J.E. Hwang, W.K. Bae, D. Lee, T. Yoon, J.K. Lee, S.C. Lim, W.K. Chung, J.S. Ahn, S.I. Jung, Y.D. Choi, I.J. Chung
Journal: Annals of Oncology (2014)
Adenovirus demonstrated by immunofluorescence.
Authors: P S Gardner, R McGuckin, J McQuillin
Journal: BMJ (1972)

lung metastases of adenocarcinoma of the colon in another.A temporary improvement in neurological signs occurred in another patient with spinal deposits of adenocarcinoma of the colon.In a patient with lung and liver metastases of rectal adenocarcinoma there was a reduction in the size of the liver, but this may have been due to treatment of congestive cardiac failure with digoxin and diuretics.There was no improvement in two patients with metastases of anaplastic carcinoma of the breast and ovary although the latter showed exceptionally high F.D.P. levels (1,500 ,ug/ml) during treatment.Fibrin degradation products have been observed in women with malignant ovarian metastases,2 3and may be derived from breakdown of plasma fibrin following release of thromboplastic substances into the circu- lation.We suggest that some of the F.D.P. occurring during ancrod therapy may be de- rived not only from the expected breakdown of microclots in the circulation but also from degradation of fibrin filaments in the tumour.It may well be that the malignant cells are exposed free from their surrounding sheath of fibrin filament and may perhaps be more susceptible to cytotoxic therapy.-We are, etc.,
Lack of effect of pregnancy on outcome of melanoma
Authors: R.M. MacKie, R. Bufalino, A. Morabito, N. Cascinelli, C. Sutherland, B.R. Kroon, M. Urist, F. Lejeune, J.A. Hunter, J. Gohl, L. Santi, H. Schmitt, H. Holmstrom, K. Wozniak, P. von Wussow, P. Craig, C. Aubert, H. Shibata, J. Priario, N. Trapeznikov, J. Durandi, D.C. Bandiera, E. Szekeres, G. Milton, M.F. Avril, A. Kulakowski, R. Panizzon
Journal: The Lancet (1991)
Functional Consequences of Mutations in Postsynaptic Scaffolding Proteins and Relevance to Psychiatric Disorders
Authors: Jonathan T. Ting, João Peça, Guoping Feng
Journal: Annual Review of Neuroscience (2012)

Functional studies on postsynaptic scaffolding proteins at excitatory synapses have revealed a plethora of important roles for synaptic structure and function. In addition, a convergence of recent in vivo functional evidence together with human genetics data strongly suggest that mutations in a variety of these postsynaptic scaffolding proteins may contribute to the etiology of diverse human psychiatric disorders such as schizophrenia, autism spectrum disorders, and obsessive-compulsive spectrum disorders. Here we review the most recent evidence for several key postsynaptic scaffolding protein families and explore how mouse genetics and human genetics have intersected to advance our knowledge concerning the contributions of these important players to complex brain function and dysfunction.
Insertion bias and purifying selection of retrotransposons in the Arabidopsis thalianagenome
Authors: Vini Pereira
Journal: Genome biology (2004)

Abstract Background Genome evolution and size variation in multicellular organisms are profoundly influenced by the activity of retrotransposons. In higher eukaryotes with compact genomes retrotransposons are found in lower copy numbers than in larger genomes, which could be due to either suppression of transposition or to elimination of insertions, and are non-randomly distributed along the chromosomes. The evolutionary mechanisms constraining retrotransposon copy number and chromosomal distribution are still poorly understood. Results I investigated the evolutionary dynamics of long terminal repeat (LTR)-retrotransposons in the compact Arabidopsis thaliana genome, using an automated method for obtaining genome-wide, age and physical distribution profiles for different groups of elements, and then comparing the distributions of young and old insertions. Elements of the Pseudoviridae family insert randomly along the chromosomes and have been recently active, but insertions tend to be lost from euchromatic regions where they are less likely to fix, with a half-life estimated at approximately 470,000 years. In contrast, members of the Metaviridae (particularly Athila ) preferentially target heterochromatin, and were more active in the past. Conclusion Diverse evolutionary mechanisms have constrained both the copy number and chromosomal distribution of retrotransposons within a single genome. In A. thaliana , their non-random genomic distribution is due to both selection against insertions in euchromatin and preferential targeting of heterochromatin. Constant turnover of euchromatic insertions and a decline in activity for the elements that target heterochromatin have both limited the contribution of retrotransposon DNA to genome size expansion in A. thaliana .
Phylogenetic diversification of immunoglobulin genes and the antibody repertoire.
Authors: G W Litman, J P Rast, M J Shamblott, R N Haire, M Hulst, W Roess, R T Litman, K R Hinds-Frey, A Zilch, C T Amemiya
Journal: Molecular Biology and Evolution (1993)

Immunoglobulins are encoded by a large multigene system that undergoes somatic rearrangement and additional genetic change during the development of immunoglobulin-producing cells. Inducible antibody and antibody-like responses are found in all vertebrates. However, immunoglobulin possessing disulfide-bonded heavy and light chains and domain-type organization has been described only in representatives of the jawed vertebrates. High degrees of nucleotide and predicted amino acid sequence identity are evident when the segmental elements that constitute the immunoglobulin gene loci in phylogenetically divergent vertebrates are compared. However, the organization of gene loci and the manner in which the independent elements recombine (and diversify) vary markedly among different taxa. One striking pattern of gene organization is the "cluster type" that appears to be restricted to the chondrichthyes (cartilaginous fishes) and limits segmental rearrangement to closely linked elements. This type of gene organization is associated with both heavy- and light-chain gene loci. In some cases, the clusters are "joined" or "partially joined" in the germ line, in effect predetermining or partially predetermining, respectively, the encoded specificities (the assumption being that these are expressed) of the individual loci. By relating the sequences of transcribed gene products to their respective germ-line genes, it is evident that, in some cases, joined-type genes are expressed. This raises a question about the existence and/or nature of allelic exclusion in these species. The extensive variation in gene organization found throughout the vertebrate species may relate directly to the role of intersegmental (V<==>D<==>J) distances in the commitment of the individual antibody-producing cell to a particular genetic specificity. Thus, the evolution of this locus, perhaps more so than that of others, may reflect the interrelationships between genetic organization and function.