tbuckley/cabot-search huggingface dataset:
Localization of pro-opiomelanocortin mRNA transcripts and peptide immunoreactivity in rat heart
Authors: William R Millington, David W Rosenthal, Can B Unal, Cynthia Nyquist-Battie
Journal: Cardiovascular Research (1999)

Objective: α-Melanocyte-stimulating hormone (α-MSH), β-endorphin and other pro-opiomelanocortin- (POMC) derived peptides have been detected in the heart, but it is uncertain whether they are synthesized by cardiomyocytes or by cardiac nerves innervating the heart. The objective of this study was to determine whether POMC peptides are synthesized by cardiomyocytes. Methods: Pro-opiomelanocortin peptides were localized in rat heart by immunohistochemistry using antisera against α-MSH, β-endorphin and αN-acetyl-β-endorphin, the predominant POMC peptides found in heart. Pro-opiomelanocortin mRNA was investigated by reverse transcription polymerase chain reaction (RT-PCR) using primers that discriminate between full-length POMC mRNA and a 5′ truncated POMC transcript that is presumed to be non-functional. Results: α-Melanocyte-stimulating hormone, β-endorphin and αN-acetyl-β-endorphin immunoreactivities were localized in atrial myocytes, particularly in the atrial appendages, but not to a significant extent in ventricular myocytes. Cardiac nerves were not immunostained. Atrial natriuretic peptide (ANP) immunoreactivity was similarly distributed in the adult heart. In neonatal heart, POMC-peptide and ANP immunoreactivities were present in both atrial and ventricular myocytes. RT-PCR amplification showed that full-length POMC mRNA transcripts were present in both atrial and ventricular tissue and provide evidence that 5′ truncated POMC mRNA is expressed in heart. Conclusions: These results support the hypothesis that cardiomyocytes synthesize POMC peptides.
Distribution of immunoreactive endothelin in the lungs of mice during respiratory viral infection
Authors: MJ Carr, LJ Spalding, RG Goldie, PJ Henry
Journal: European Respiratory Journal (1998)

Respiratory tract viral infections are associated with the generation of a wide array of pro-inflammatory cytokines, some of which enhance the release of the potent airway smooth muscle spasmogen, endothelin, from respiratory epithelial cells in tissue culture. The aim of this study was to determine whether the content and distribution of immunoreactive endothelin in the intact murine lung is increased during the course of a respiratory tract viral infection. Mice were inoculated intranasally with Influenza A/PR-8/34 virus or sterile vehicle and at various days postinoculation were sacrificed, and their lungs processed for either fluorescence immunohistochemistry with rabbit anti-endothelin sera or measurement of immunoreactive endothelin with an enzyme-linked immunosorbent assay (ELISA). At 2 and 4 days postinoculation, the content of immunoreactive endothelin in lung extracts of virus-infected mice was approximately twice that present in lung extracts from control mice (n=3-4, p&lt;0.05). Consistent with this, an increased intensity and broader distribution of fluorescent immunohistochemical staining for endothelin was observed in the airway epithelium of the trachea and intrapulmonary airways of virus-infected mice. This study has clearly demonstrated that respiratory tract viral infection is associated with an increased content and broader distribution of immunoreactive endothelin within the lungs of mice. Whether the elevated content of endothelin contributes to the symptoms of virus-induced hyperresponsiveness or to virus-induced exacerbations of asthma remains to be established.
Fixed Bicortical Screw and Blade Implants as a Non‐Standard Solution to an Edentulous (Toothless) Mandible
Authors: Juraj Strecha, Richard Jurkovic, Tomas Siebert, Patrik Prachar, Sonia Bartakova
Journal: International Journal of Oral Science (2010)

This paper deals with the treatment of an atrophied toothless mandible with a fixing bridge carried by two non‐standard implant systems. Four bicortical screws were implanted into the frontal part of the mandible and one implant on each side was placed into the distal area of the mandible as a support for a fixing bridge. During the years 2002 – 2007 the authors placed a total of 256 bicortical screw and 84 blade implants. During this period only four bicortical screws and one blade implant failed. The primary and secondary surgical success rate was therefore above 98%, while the prosthetic success rate was 100%. (Bridges which had to be re‐fabricated due to implant failure were not taken into account.) This approach is recommended as a highly successful and affordable option for a wide range of patients.
Platelet associated immunoglobulins in primary biliary cirrhosis: a cause of thrombocytopenia?
Authors: M F Bassendine, J D Collins, J Stephenson, P Saunders, O F James
Journal: Gut (1985)

Thrombocytopenia in cirrhotic patients is usually attributed to splenic pooling whereas in idiopathic thrombocytopenic purpura it is related to platelet bound immunoglobulin (PA-IgG). Since primary biliary cirrhosis (PBC) is an autoimmune disorder we have undertaken a prospective study to assess the frequency and possible relationship of PA-IgG to thrombocytopenia in this condition. Sixty-two primary biliary cirrhosis patients (28 precirrhotic; 34 cirrhotic) were studied. Twenty-five patients (40%) had raised PA-IgG of whom 18 had cirrhosis. There was a significant inverse correlation between platelet count and PA-IgG (p less than 0.001) and between platelet count and spleen size (p less than 0.001). Thrombocytopenia (platelets less than 100 X 10(9)/l) was found in nine patients (15%); all nine had raised PA-IgG and eight were cirrhotic with an enlarged spleen. Two cirrhotic patients with persistent thrombocytopenia and bleeding episodes were treated with prednisolone and showed a useful therapeutic response. These results suggest that immune mediated platelet destruction and splenic pooling of platelets may both play a part in the thrombocytopenia observed in primary biliary cirrhosis.
Isolation and characterization of IgG molecules expressing latent group b allotypes from pedigreed b4b4 rabbits.
Authors: M L Yarmush, T J Kindt
Journal: The Journal of Experimental Medicine (1978)

Latent group b markers were detected in sera, in IgG preparations, and on isolated L chains from rabbits bred for homozygosity at the b locus. Serologic analysis of sera from an extended family of homozygous b4 rabbits revealed the presence of latent b allotypes in 5 of 37 sera tested. Latent b5 and b9 markers were identified; none of the sera tested contained latent b6. In two instances, the level of latent b9 allotypes was sufficiently high to permit isolation and detailed serologic characterization of the immunoglobulin population bearing this allotype. The fact that latent allotypes were detected in pedigreed homozygous rabbits minimizes the possibility that lymphoid cell chimerism is involved in latent allotype expression. Furthermore, characterization of the b9 IgG population indicates that the latent allotypic determinants do not reside on a subset of molecules with dual allotypic reactivity.
The EFFECTS of VACCINATING DURING a MENSTRUAL PERIOD
Authors: E. R. Dawson
Journal: BMJ (1903)

VACClNATION DURING MENSTRUATION.TM 303 4 lb. in weight, and was able to walk ten miles a day, while her temperature remained normal.The physical signs, how- ever, were unaltered, except that the breath sounds were now quite absent in the dull area.By Christmas she had gained 8 lb., in spite of a febrile attack of "bronchial catarrl " in November-for which she was attended by Dr. Fraser, of Carlton-and felt very well, but was again spitting large quantities of phlegm.Suspecting hydatids, I repeatedly sought for fragments of membrane in the sputum, but in vain.During the whole of February she was in bed, under Dr. Fraser's care, with signs of general catarrh of the left lung, fever, and incessant cough.When I saw her again in April she was, therefore, not so well, had lost flesh, and complained of pains in the front of the left half of the chest and in the axilla, while she coughed a good deal of frothy, watery fluid.There was now heard pleuritic friction in the axilla outside the dull area, which had slightly extended.Although there was no history of syphilis, she had been taking potassium iodide in large doses for nearly four months.Didgnosis.-Feeling that hydatid cyst in the pleural cavity in front of the lelt lung was a probable diagnosis, I now urged her not longer to postpone surgical treatment, which Mr. Morley Willis after consultation agreed to carry out, de-
Persistence of immunoglobulin-producing cells in parotid salivary glands of patients with primary Sjögren's syndrome after B cell depletion therapy
Authors: Nishath Hamza, Hendrika Bootsma, Saravanan Yuvaraj, Fred K L Spijkervet, Erlin A Haacke, Rodney P E Pollard, Annie Visser, Arjan Vissink, Cees G M Kallenberg, Frans G M Kroese, Nicolaas A Bos
Journal: Annals of the Rheumatic Diseases (2012)

Objectives To assess the persistence of immunoglobulin-producing cell populations in the parotid salivary glands of patients with primary Sjögren's syndrome (pSS) after B cell depletion therapy with rituximab. Methods Thirteen patients with pSS and four control patients were included in this study. Patients with pSS were treated with rituximab or placebo. Sequence analysis was carried out on IgA- and IgG-encoding transcripts extracted from parotid salivary gland biopsy specimens taken before treatment and at 12–16 and 36–52 weeks after treatment. Results At baseline, many clonally related sequences were seen in patients with pSS. The number of clonal expansions was significantly higher in patients with pSS than in control patients. Clonal expansions were composed of IgA- and/or IgG-expressing cells. Rituximab did not significantly alter the degree of clonal expansions. Groups of clonally related cells had members which were shared between biopsy specimens taken before and after treatment. Mutation frequencies of immunoglobulin sequences from clonally related cells in patients with pSS were higher after treatment. Conclusions Rituximab treatment does not alter the characteristic features of increased clonal expansions seen in the parotid salivary glands of patients with pSS. The presence of clonally related immunoglobulin-producing cells before and after rituximab treatment strongly suggests that immunoglobulin-producing cells persist in salivary glands of patients with pSS despite B cell depletion. The presence of mixed isotype expression within groups of clonally related cells indicates local class switching in salivary glands of patients with pSS. Persistent immunoglobulin-producing cells may underlie disease relapse after treatment.
Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis
Authors: Mélanie Drolet, Élodie Bénard, Marie-Claude Boily, Hammad Ali, Louise Baandrup, Heidi Bauer, Simon Beddows, Jacques Brisson, Julia M L Brotherton, Teresa Cummings, Basil Donovan, Christopher K Fairley, Elaine W Flagg, Anne M Johnson, Jessica A Kahn, Kimberley Kavanagh, Susanne K Kjaer, Erich V Kliewer, Philippe Lemieux-Mellouki, Lauri Markowitz, Aminata Mboup, David Mesher, Linda Niccolai, Jeannie Oliphant, Kevin G Pollock, Kate Soldan, Pam Sonnenberg, Sepehr N Tabrizi, Clare Tanton, Marc Brisson
Journal: The Lancet Infectious Diseases (2015)
Functional characterization of the human tumor necrosis factor receptor p75 in a transfected rat/mouse T cell hybridoma.
Authors: P Vandenabeele, W Declercq, D Vercammen, M Van de Craen, J Grooten, H Loetscher, M Brockhaus, W Lesslauer, W Fiers
Journal: The Journal of Experimental Medicine (1992)

We investigated the biological role of the human tumor necrosis factor p75 (hTNF-R75), making use of the species specificity of TNF responses in murine (m) T cell lines. Several TNF-mediated activities on mouse T cells, such as cytokine induction or proliferation, showed a 100-500-fold difference in specific biological activity between mTNF and hTNF. After transfection of hTNF-R75 cDNA in a rat/mouse T cell hybridoma (PC60), however, the 100-fold lower specific biological activity of hTNF was converted to the same specific biological activity as mTNF. The TNF-mediated induction of granulocyte/macrophage colony-stimulating factor was strongly synergized by the addition of interleukin 1. In the presence of the latter cytokine, ligand-competing monoclonal antibodies against hTNF-R75 (utr-1, utr-2, utr-3) were agonistic on transfected PC60 cells. This agonistic activity was further enhanced by crosslinking with sheep anti-murine immunoglobulin antibodies. These data provide direct evidence for a functional role of TNF-R75, without ligand-dependent TNF-R55 involvement, in the induction of cytokine secretion in T cells.
Basal lamina heterogeneity in the glomerular capillary tufts of human kidneys
Authors: TW Huang
Journal: The Journal of Experimental Medicine (1979)

Two classes of glomerular basal laminas are identified with a newly developed guanidine technique. The electron-opaque epithelial basal lamina is the most prominent element of the glomerular basal lamina scaffold. It is a continuous layer within each glomerulus, folding into capillary tufts and loops, but never completely encircling the entire circumference of each capillary, similar to the serosa covering the intestinal loop and mesentery. The vascular space so defined is further partitioned into individual capillary lumen by an electron-lucent mesangial basal lamina, that forms a meshwork continuous with the vascular pole of the glomerulus and extends peripherally to surround capillary lumens. The latter, designated endothelial basal lamina, is extremely attenuated and appears as a vestigial structure in glomerular capillary loops. Changes in juxtamesangial epithelial basal lamina indicate that it may be the site of the bulk removal and renewal of the epithelial basal lamina. The unique epithelial origin of glomerular capillary basal lamina and its organization provide a structural basis for understanding the glomerular physiology gained by various tracer studies. The results also suggest that the guanidine technique may be a useful new approach to the analysis of basal lamina alterations in various glomerular diseases.
Abstract 312: Regulation of Fibrotic Signaling Pathways by Desmosomal Armadillo Proteins in Cardiac Tissue
Authors: Adi D Dubash, Kathleen J Green
Journal: Circulation Research (2014)

The process of fibrosis, described as accumulation of myofibroblasts and excessive deposition of extracellular matrix components, is a key development in the progression of multiple different types of cardiac disease. Nevertheless, little is known about the molecular mechanisms which cause the onset of fibrosis in cardiac disease. Fibrosis is a significant component of arrhythmogenic cardiomyopathy (AC), a genetic disorder characterized by replacement of healthy cardiomyocytes (CMs) with fibrous tissue, leading to arrhythmia and in certain cases, sudden death. AC is often characterized as a “disease of the desmosome”, as mutations for all obligate desmosome proteins have been found in cases of AC, including the desmosome armadillo proteins Plakophilin-2 (PKP2) and Plakoglobin (PG). PKP2 and PG are multi-functional proteins involved in both mechanical stabilization of the cardiac area composita, as well as mediation of desmosome-related signaling pathways. We have determined that loss of PKP2 or PG in neonatal CMs causes an aberrant increase in gene expression of pro-fibrotic stimuli such as transforming growth factor beta 1 (TGF-beta1) and Interleukin-6 (IL-6). In addition, p38 MAPK, a known mediator of inflammatory fibrosis, is activated upon loss of PKP2/PG. We hypothesize that mutation or loss of PKP2 or PG cause the recruitment and activation of cardiac fibroblasts via pro-fibrotic TGF-beta and p38MAPK signaling, resulting in pathological fibrosis characteristic of AC. Indeed, conditioned media from PKP2-silenced CMs causes an increase in fibronectin gene expression by freshly isolated cardiac fibroblasts. Our future experiments will investigate whether inhibition of TGF-beta or p38MAPK signaling can alleviate fibrotic gene production. By highlighting a novel link between desmosome armadillo proteins and pro-fibrotic signaling in cardiac tissue, this study provides mechanistic insights into the pathogenesis of AC, as well as advances our knowledge of potential therapeutic targets for combating fibrosis in multiple different types of heart disease or injury.
Increased Osmolal Gap in Alcoholic Ketoacidosis and Lactic Acidosis
Authors: Jeffrey R. Schelling
Journal: Annals of Internal Medicine (1990)

Objective: To determine whether an elevated osmolal gap is specific for toxic alcohol ingestion. Design: Cross-sectional. Setting: Emergency room and medical and surgical inpatient wards at a university-affiliated hospital. Patients: Twenty-three patients with lactic acidosis, 19 with alcoholic ketoacidosis, and 10 randomly selected controls. Measurements and Main Results: Calculated and measured serum osmolality was determined in all study participants. The osmolal gap was increased in patients with lactic acidosis (17.4 ± 5.4 mmol/kg) and alcoholic ketoacidosis (26.9 ±7.6 mmol/kg) when compared with controls (- 1.7 ±1.7 mmol/kg, P < 0.05 for both comparisons). When ethanol was included in the calculation, the osmolal gap remained elevated in the lactic acidosis (10.3 ±2.0 mmol/kg) and alcoholic ketoacidosis (11.1 ±3.2 mmol/kg) groups (P < 0.05 for both comparisons). Conclusions: The osmolal gap is often used as a screen for toxic alcohol ingestion. When calculating the osmolal gap, the contribution of ethanol should be considered. An elevated osmolal gap is not specific for toxic alcohol ingestion, as the osmolal gap was elevated in patients with lactic acidosis and alcoholic ketoacidosis. These two conditions should be considered when using the osmolal gap to design therapy (for example, hemodialysis) in the setting of anion gap metabolic acidosis and suspected toxic alcohol ingestion.
Does the Benefit Justify the Risk?
Authors: P. C. Albertsen
Journal: JNCI Journal of the National Cancer Institute (2009)

The past two decades have witnessed a dramatic increase in the number of men who have been diagnosed with prostate cancer. Since the introduction of prostate-specific antigen (PSA) testing, approximately 90 000 additional men have been diagnosed annually and large numbers of these men have received treatments, such as radical prostatectomy, radiation therapy, or androgen deprivation therapy (ADT). Before the widespread use of PSA screening, an American man had an 8.7% lifetime risk of being diagnosed with prostate cancer and a 2.5% risk of dying from this disease ( 1 ). By 2005, the lifetime risk of being diagnosed had increased to 17%, whereas the lifetime risk of dying from prostate cancer remained virtually unchanged ( 2 ). PSA screening has dramatically changed the type of patient presenting with newly diagnosed disease. Men now rarely present with symptoms. Between 1996 and 2004, most men (91%) were diagnosed with local or regional disease ( 2 ). The rational for treating these men is no longer to relieve symptoms but rather to prevent prostate cancer progression. Unfortunately, data from randomized trials are sparse concerning the effi cacy of this approach.
Biochemical evidence linking the GIX thymocyte surface antigen to the gp69/71 envelope glycoprotein of murine leukemia virus.
Authors: J S Tung, E S Vitetta, E Fleissner, E A Boyse
Journal: The Journal of Experimental Medicine (1975)

It is known that the thymocyte surface antigen GIX is found in some strains of mice and not others, and that its expression in mice of strain 129, in which most extensive genetic studies have been made, is controlled by two unlinked cellular chromosomal loci. We have now isolated a protein with a mol wt of approximately 70,000 daltons from the surface of thymocytes from 129 mice, which have antigenic and biochemical properties characteristic of the gp69/71 envelope component of murine leukemia virus. Our evidence is compatible with the conclusion that it carries the GIX antigen.
Ia determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells.
Authors: H S Ko, S M Fu, R J Winchester, D T Yu, H G Kunkel
Journal: The Journal of Experimental Medicine (1979)

Human T-cell blasts were generated by stimulation with mitogens and antigens. A proportion of these blasts expressed Ia antigens detectable by immunofluorescence with both allo- and hetero-antiserums. The maximal expression of Ia antigens was delayed and usually occurred after the peak of blastogenesis. Among the three mitogens used, pokeweed mitogen (PWM) was most effective in giving a high percentage and intense Ia staining of T-cell blasts. Phytohemagglutinin and concanavalin A blasts gave weaker and lower percentages of Ia staining. Activation by alloantigens and soluble antigens such as tetanus toxoid and purified protein derivative resulted in Ia expression on T cells comparable to PWM stimulation. Depletion of Ia+ cells from freshly isolated T cells with anti-Ia and complement decreased subsequent Ia expression, suggesting that a proportion of Ia+ blasts were derived from Ia-bearing peripheral blood T cells. When the specificities of the Ia antigens on T-cell blasts were examined with alloantiserums, it was evident that the T blasts expressed similar HLA-DR determinants to those on B cells from the same donor; occasional minor differences between stimulated T cells and autologous B-cell lines or fresh B cells were encountered.