tbuckley/cabot-search huggingface dataset:
CD44 Expression Is Associated with Increased Survival in Node-Negative Invasive Breast Carcinoma
Authors: Leslie K. Diaz, Xiao Zhou, Edward T. Wright, Massimo Cristofanilli, Terry Smith, Ying Yang, Nour Sneige, Aysegul Sahin, Michael Z. Gilcrease
Journal: Clinical Cancer Research (2005)

Abstract Purpose: CD44 is a multifunctional cell surface receptor with many known splice variants, some of which have been reported to play a role in tumor progression. The purpose of this study was to evaluate the prognostic significance of CD44 isoforms in early-stage, lymph node–negative invasive breast carcinoma. Experimental Design: Immunohistochemical staining for CD44 isoforms was done on archival paraffin tissue sections of invasive breast carcinoma from a cohort of lymph node–negative patients who received no adjuvant tamoxifen or chemotherapy and who had a mean clinical follow-up period of 15 years. Immunohistochemical staining was done with antibodies to CD44s, the standard isoform of CD44, and to isoforms containing variant exon 6 (CD44v6); levels of staining were correlated with clinical outcome data. Results: There was a trend towards increased disease-free survival for patients whose tumors had high anti-CD44s positivity (P = 0.05), and a significant association was observed between anti-CD44s positivity and disease-related survival (P = 0.04). Expression of CD44v6 isoforms did not correlate with clinical outcome. Conclusion: CD44 expression, as assessed by immunohistochemical staining with anti-CD44s, may be a favorable prognostic factor in patients with node-negative invasive breast carcinoma.
<i>PRSS1</i>c.623G&gt;C (p.G208A) variant is associated with pancreatitis in Japan: Table 1
Authors: Atsushi Masamune, Eriko Nakano, Kiyoshi Kume, Tetsuya Takikawa, Yoichi Kakuta, Tooru Shimosegawa
Journal: Gut (2013)

We read with great interest the article by Schnur et al 1 reporting the functional effects of 13 serine protease 1 ( PRSS1 ) variants found in sporadic chronic pancreatitis (CP). They reported that five mutants, including p.G208A, showed reduced secretion, suggesting that these variants might increase the risk of pancreatitis related to mutation-induced misfolding and consequent endoplasmic reticulum stress. The pathological role of these variants might be strengthened by their association with pancreatitis cohorts, but such information is scarce. Interestingly, the c.623G>C (p.G208A) variant has been reported only in Asian subjects: a 12-year-old Asian man with CP, a Korean child with recurrent pancreatitis and a 7-year-old Korean child with necrotising acute pancreatitis.2 ,3 We therefore conducted screening of the PRSS1 p.G208A variant in Japanese patients with CP. All of the exons and the flanking regions in …
Linkage Group V of Platyfishes and Swordtails of the Genus &lt;italic&gt;Xiphophorus&lt;/italic&gt; (Poeciliidae): Linkage of Loci for Malate Oehydrogenase-2 and Esterase-1 and Esterase-4 With a Gene ContrOlling the Severity of Hybrid Melanomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: D C Morizot, M J Siciliano
Journal: JNCI Journal of the National Cancer Institute (1983)

Electrophoretic variations ascribable to three enzyme loci coding for esterase-1 and -4 (ES1 and ES4) and a malate dehydrogenase-2 isozyme (MDH2) were studied in interspecific backcrosses of fishes of the genus Xiphophorus (Poeciliidae). Normal segregation was demonstrated for all three loci. Linkage analyses indicated a gene order of ES1-6%-ES4-33%-MDH2. This group [designated linkage group (LG) V] was shown to assort independently from the 11 loci comprising LG's I-IV and from 18 other informative markers, with the limits of the data. A factor controlling the extent of development of inherited melanomas was demonstrated to be associated only with LG V loci, implying predominant control by a single gene, which probably determines the completeness of differentiation of macromelanophores in hybrids. Possible explanations for variability in the apparent chromosomal position of the melanoma severity gene, as assessed by estimates of recombination with the LG V enzyme loci, are discussed.
Effects of erythromycin on<i>Pseudomonas aeruginosa</i>adherence to collagen and morphology<i>in vitro</i>
Authors: K.W. Tsang, P. Ng, P.L. Ho, S. Chan, G. Tipoe, R. Leung, J. Sun, J.C. Ho, M.S. Ip, W.K. Lam
Journal: European Respiratory Journal (2003)

The airways of patients with bronchiectasis and cystic fibrosis are often chronically colonised by Pseudomonas aeruginosa (PA), which is virtually impossible to eradicate. Low-dose erythromycin (EM), for unknown mechanisms, is efficacious in bronchiectasis and diffuse panbronchiolitis. In this study, an in vitro model to investigate PA adherence to human type IV basement collagen was developed by using scanning electron microscopy (SEM). There were significantly less PA bacilli per 20 random SEM fields (4,000×) when PA was cultured in 0.05, 0.5 and 5 µg·mL −1 of EM compared with control (absence of EM). Adherence density (20 SEM fields·log −1 inocular size) for PA obtained from no EM (56.8±43.16) was significantly higher than that obtained from 0.05, 0.5, and 5 µg·mL −1 EM (21.5±17.56, 23.3±16.65, and 21.4±12.65 respectively). By using SEM it was found that PA, when incubated in EM (0.05, 0.5, 5 µg·mL −1 ) had a significant reduction in its diagonal length, radius, height, volume and surface area. It is possible, therefore, that these misshaped Pseudomonas aeruginosa bacilli are more susceptible to host defence mechanisms, while at the same time less adherent to the basement membrane of the airway in vivo . Therefore, this could help explain the clinical efficacy of low-dose erythromycin therapy on patients with Pseudomonas aeruginosa infection.
Synergistic Cytotoxicity in Solid Tumor Cell Lines Between N-(4-Hydroxyphenyl)retinamide and Modulators of Ceramide Metabolism
Authors: B. J. Maurer
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: We previously reported that N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide) treatment caused large increases of ceramide levels in neuroblastoma cell lines and induced cell death by a combination of apoptosis and necrosis through p53 (also known as TP53)-independent and caspase-independent pathways. Our goal was to determine if several molecules that inhibit enzymes involved in ceramide metabolism—l-threo-dihydrosphingosine (safingol), d,l-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol (PPMP), and tamoxifen—enhanced 4-HPR-mediated cytotoxicity and/or affected ceramide levels. Methods: Cellular lipids were quantified by radiolabeling and thin-layer chromatography. Cytotoxicity and cytotoxic synergy (expressed as combination index, where combination index <1 indicates synergy and >1 indicates antagonism) were measured in cultured cancer cell lines with the use of a fluorescence-based assay of cell viability employing digital imaging microscopy. Statistical tests were two-sided. Results: 4-HPR increased ceramide levels by de novo synthesis. Safingol (1–4 μM) was incorporated into a stereochemical variant of ceramide and synergized with a 3 : 1 molar ratio of 4-HPR (3–12 μM), to produce a 100-fold to 10 000-fold (2 to 4 logs) increase in cytotoxicity relative to 4-HPR alone in neuroblastoma (combination index <0.1), lung (combination index <0.1–0.2), melanoma (combination index <0.1–0.2), prostate (combination index <0.1–1.0), colon (combination index 0.1–0.3), breast (combination index = 0.1–0.5), and pancreas (combination index = 0.2) cell lines, including p53 mutant and alkylator-resistant cell lines. The 4-HPR and safingol combination was cytotoxic in low-oxygen conditions and was minimally toxic to normal fibroblasts and bone marrow myeloid progenitor cells. Addition of agents that retard ceramide glucosylation and/or acylation, such as PPMP or tamoxifen, to 4-HPR or to the combination of 4-HPR and safingol further increased cytotoxicity to tumor cells. Conclusions: Combinations of 4-HPR and modulators of ceramide metabolism may form the basis for a novel chemotherapy that is functional under hypoxic conditions (e.g., such as those within tumors) and is p53 independent and caspase independent.
Subset derivation of T-cell acute lymphoblastic leukemia in man.
Authors: E L Reinherz, L M Nadler, S E Sallan, S F Schlossman
Journal: Journal of Clinical Investigation (1979)

Normal human peripheral blood T cells can be characterized as belonging to either the TH+2 or TH-2 T-cell subset. Approximately 20% of T cells are TH+2, whereas 80% are TH-2 utilizing specific heteroantisera. To determine shether human T-cell acute lymphoblastic leukemia (T-ALL) cells belong to one or another T-cell subset, cell surface phenotyping was performed on tumor populations from 25 patients with T-ALL. Tmuor cells from these 25 individuals were either TH+1 or TH-2, but not both. 5 of 25 patients had TH+2 T-ALL cells. These TH+2 tumor populations were found exclusively in children and often without an accompanying thymic mass. TH-2 T-ALL, in contrast, occurred in both children and adults and was almost always associated with thymic enlargement. Although children with TH+2 T-ALL had as high or higher peripheral blast counts on presentation than their TH-2 T-ALL counterparts, overall survival was greater for the TH+2 group (greater than 36 mo) than the TH-2 group (less than 12 mo). These studies demonstrate that T-cell leukemias in man arise from distinct T-cell subsets and that cell surface characterization of T-cell malignancies may provide useful clinical data related to prognosis.
Role of CXCL13 in Cigarette Smoke–induced Lymphoid Follicle Formation and Chronic Obstructive Pulmonary Disease
Authors: Ken R. Bracke, Fien M. Verhamme, Leen J. M. Seys, Claudie Bantsimba-Malanda, Danen Mootoosamy Cunoosamy, Ronald Herbst, Hamida Hammad, Bart N. Lambrecht, Guy F. Joos, Guy G. Brusselle
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

The B cell-attracting chemokine CXCL13 is an important mediator in the formation of tertiary lymphoid organs (TLOs). Increased numbers of ectopic lymphoid follicles have been observed in lungs of patients with severe chronic obstructive pulmonary disease (COPD). However, the role of these TLOs in the pathogenesis of COPD remains unknown.By neutralizing CXCL13 in a mouse model of chronic cigarette smoke (CS) exposure, we aimed at interrogating the link between lymphoid follicles and development of pulmonary inflammation, emphysema, and airway wall remodeling.We first quantified and localized CXCL13 in lungs of air- or CS-exposed mice and in lungs of never smokers, smokers without airflow obstruction, and patients with COPD by reverse transcriptase-polymerase chain reaction, ELISA, and immunohistochemistry. Next, CXCL13 signaling was blocked by prophylactic or therapeutic administration of anti-CXCL13 antibodies in mice exposed to air or CS for 24 weeks, and several hallmarks of COPD were evaluated.Both mRNA and protein levels of CXCL13 were increased in lungs of CS-exposed mice and patients with COPD. Importantly, expression of CXCL13 was observed within B-cell areas of lymphoid follicles. Prophylactic and therapeutic administration of anti-CXCL13 antibodies completely prevented the CS-induced formation of pulmonary lymphoid follicles in mice. Interestingly, absence of TLOs attenuated destruction of alveolar walls and inflammation in bronchoalveolar lavage but did not affect airway wall remodeling.CXCL13 is produced within lymphoid follicles of patients with COPD and is crucial for the formation of TLOs. Neutralization of CXCL13 partially protects mice against CS-induced inflammation in bronchoalveolar lavage and alveolar wall destruction.
Climate change, extreme weather events, air pollution and respiratory health in Europe
Authors: M. De Sario, K. Katsouyanni, P. Michelozzi
Journal: European Respiratory Journal (2013)

Due to climate change and other factors, air pollution patterns are changing in several urbanised areas of the world, with a significant effect on respiratory health both independently and synergistically with weather conditions; climate scenarios show Europe as one of the most vulnerable regions. European studies on heatwave episodes have consistently shown a synergistic effect of air pollution and high temperatures, while the potential weather–air pollution interaction during wildfires and dust storms is unknown. Allergen patterns are also changing in response to climate change, and air pollution can modify the allergenic potential of pollens, especially in the presence of specific weather conditions. The underlying mechanisms of all these interactions are not well known; the health consequences vary from decreases in lung function to allergic diseases, new onset of diseases, exacerbation of chronic respiratory diseases, and premature death. These multidimensional climate–pollution–allergen effects need to be taken into account in estimating both climate and air pollution-related respiratory effects, in order to set up adequate policy and public health actions to face both the current and future climate and pollution challenges.
Applied Biopharmaceutics and Pharmacokinetics.
Journal: Annals of Internal Medicine (1981)

Mathematical fundamentals on pharmacokinetics introduction to biopharmaceutics and pharmacokinetics one compartment model physiological factors relating to drug absorption biopharmaceutic considerations in drug product design modified release drug products delivery of biotechnical products and targetted drug delivery systems pharmacokinetics of drug absorption bioavailability and bioequivalence multicompartmental models drug distribution and protein binding drug clearance drug metabolism and hepatic clearance pharmacokinetics after intravenous infusion pharmacokinetics after multiple dosing non-linear pharmacokinetics introduction to clinical pharmacokinetics application of pharmacokinetics to clinical situations relationship between pharmacokinetic parameters and pharmacologic response physiologic pharmacokinetic model and statistical moment computer applications in pharmacokinetics biopharmaceutics and pharmacokinetic studies in drug development appendix.
Rare cause of upper gastrointestinal bleeding in a 27-year-old male patient
Authors: Dominik Bettenworth, Emile Rijcken, Klaus-Michael Müller, Angelika Mosch-Messerich, Jan Heidemann
Journal: Gut (2012)

We report the case of a 27-year-old Caucasian man who was transferred to our hospital due to abdominal pain, bloody stools and haematemesis. The patient had no history of abdominal trauma or surgery and was in good general condition. Physical examination was normal and no signs of liver cirrhosis were evident. Laboratory findings showed marked anaemia (haemoglobin 7.3 g/dl) and slightly elevated levels of γ-glutamyltransferase (114 U/l) and alanine transaminase (86 U/l). An oesophago-gastro-duodenoscopy revealed grade IV oesophageal varices with signs of recent bleeding and several cherry red spots (figure 1A, arrows). In addition, fundic varices (figure 1B, arrow) and signs of portal hypertension were present. Endoscopic ligation of oesophageal varices was performed. However, rebleeding occurred and since no signs of underlying liver disease were evident, abdominal …
Bronchoscopy in haematopoietic stem cell transplant recipients may not be beneficial
Authors: Lydia R J Eccersley
Journal: Thorax (2007)

▴ Hofmeister CC, Czerlanis C, Forsythe S, et al . Retrospective utility of bronchoscopy after hematopoietic stem cell transplant. Bone Marrow Transplant2006 ;38:693–8.

[OpenUrl][1][CrossRef][2][PubMed][3]



Haemopoietic stem cell transplant (HSCT) recipients have a high rate of pulmonary complications, and bronchoscopy is traditionally felt to be beneficial as part of diagnostic examination. This was a retrospective review of HSCT patients in a single institution who had undergone bronchoscopy over a 10-year period; it aimed to assess whether alterations in …

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Tyrosine Phosphorylation of Tau by the Src Family Kinases Lck and Fyn
Authors: Timothy ME Scales, Pascal Derkinderen, Kit-Yi Leung, Helen L Byers, Malcolm A Ward, Caroline Price, Ian N Bird, Timothy Perera, Stuart Kellie, Ritchie Williamson, Brian H Anderton, C Hugh Reynolds
Journal: Molecular Neurodegeneration (2011)

Tau protein is the principal component of the neurofibrillary tangles found in Alzheimer's disease, where it is hyperphosphorylated on serine and threonine residues, and recently phosphotyrosine has been demonstrated. The Src-family kinase Fyn has been linked circumstantially to the pathology of Alzheimer's disease, and shown to phosphorylate Tyr18. Recently another Src-family kinase, Lck, has been identified as a genetic risk factor for this disease.In this study we show that Lck is a tau kinase. In vitro, comparison of Lck and Fyn showed that while both kinases phosphorylated Tyr18 preferentially, Lck phosphorylated other tyrosines somewhat better than Fyn. In co-transfected COS-7 cells, mutating any one of the five tyrosines in tau to phenylalanine reduced the apparent level of tau tyrosine phosphorylation to 25-40% of that given by wild-type tau. Consistent with this, tau mutants with only one remaining tyrosine gave poor phosphorylation; however, Tyr18 was phosphorylated better than the others.Fyn and Lck have subtle differences in their properties as tau kinases, and the phosphorylation of tau is one mechanism by which the genetic risk associated with Lck might be expressed pathogenically.
Baseline serum NTx levels are prognostic in metastatic breast cancer patients with bone-only metastasis
Authors: S.M. Ali, L.M. Demers, K. Leitzel, H.A. Harvey, D. Clemens, N. Mallinak, L. Engle, V. Chinchilli, L. Costa, C. Brady, J. Seaman, A. Lipton
Journal: Annals of Oncology (2004)
Carotid sinus reflex coronary vasoconstriction during controlled myocardial oxygen metabolism in the dog.
Authors: J R Powell, E O Feigl
Journal: Circulation Research (1979)

We studied carotid baroreceptor reflex coronary vasoconstriction in closed-chest dogs with controlled aortic blood pressure and myocardial oxygen metabloism. The dogs were anesthetized with morphine and chloralose. Left coronary blood flow was measured by a cannula-tip flowmeter, and myocardial oxygen metabolism was calculated by measuring the arterial-coronary sinus oxygen difference. A bilateral vagotomy was performed in all animals and they were treated with propranolol. Reduction of carotid sinus pressure to 40 mm Hg caused an increase in aortic pressure that was limited to 15 mm Hg by means of a pressure-control reservoir. During carotid hypotension, heart rate and myocardial oxygen metabolism were unchanged but diastolic conronary vascular resistance increased by 21%. Intracoronary artery infusion of norepinephrine had similar effects. After interruption of the reflex are with the alpha-adrenergic receptor antagonist, dibozane, carotid sinus hypotension and the same increase in aortic pressure (15 mm Hg) resulted in only a 5% increase in diastolic coronary resistance. Dibozane also reduced the coronary responses to norepinephrine. It is concluded that carotid sinus hypotension results in reflex sympathetic alpha-receptor coronary vasoconstriction and that this reflex vasoconstriction is independent of changes in myocardial oxygen metabolism or changes in aortic pressure.
THE PATHOLOGICAL CHANGES IN THE TESTES IN EPIDEMIC PNEUMONIA
Authors: Ralph G. Mills
Journal: The Journal of Experimental Medicine (1919)

The testicular changes in pneumonia are without clinical manifestations, are non-specific, focal in character, independent of the infecting organisms or the antecedent disease, and vary in severity directly with the total length of the illness. The process is a continuous one, divisible into stages in which the following features are recognizable: (1) cessation of spermatogenesis; (2) degeneration of preformed spermatocytes, spermatids, and spermatozoa; (3) desquamation of altered cells and fragments of the same; (4) formation of giant cells in the tubule walls with subsequent liberation into the lumen; (5) disappearance of all desquamated cells and all those derived from the spermatogonia by mitosis; (6) in some instances thickening of the hyaline layer of the basement membrane. Older lesions are frequently found which continue the structural alteration of the tubules by hyalinosis and destruction of cells until they ultimately disappear. These lesions are not believed to be connected with the present illness. Edema may represent the acute injury in another form, and round cell infiltration suggests that possibly other factors than toxins may have a part in the tissue alterations. In the absence of definite evidence to the contrary, the cause is assumed to be circulating toxins, as Wolbach (12) claims for influenzal cases. The hemolytic streptococcus produced more extensive changes, both epithelial and interstitial, in primary pneumonia occurring during the measles epidemic than when pneumonia followed as a secondary infection; in the latter cases the pulmonary complications covered a relatively shorter period. Measles and epidemic influenza had little apparent effect upon the testes, except that the former caused mild inhibition of spermatogenesis; evidence regarding the latter is inconclusive. The Pfeiffer bacillus was always associated with other organisms, in primary infections and in those following measles. It occurred alone in a few cases after epidemic influenza, but the testicular lesion was not distinctive. The pneumococcus when alone in primary infections or after an epidemic disease produced a uniformly mild picture which was not intensified when associated with the influenza bacillus. Giant cells were much more frequent after influenzal pneumonia regardless of its cause and were associated with large numbers of other desquamated cells. They are formed in the walls of tubules by futile mitotic effort and incomplete protoplasmic separation, the abnormality of the process being further suggested by the early severing of cytoplasmic attachments and rapid desquamation. The series is unique in its uniformity, in the care exercised in the bacteriological examinations, and in the relative freedom from complicating factors.