tbuckley/cabot-search huggingface dataset:
Thermal injury, intravascular hemolysis, and toxic oxygen products.
Authors: J R Hatherill, G O Till, L H Bruner, P A Ward
Journal: Journal of Clinical Investigation (1986)

Acute thermal injury of rat skin produces an early, acute hemoglobinemia that is associated with the presence in blood of osmotically fragile red cells (RBC) that do not contain on their surfaces measurable amounts of complement components. The hemoglobinemia and the appearance in blood of osmotically fragile RBC appear to be the result of complement activation, which leads to oxygen radical production by neutrophils and damage of RBC. This has been demonstrated in vitro as well as in vivo by the ability of antioxidant interventions or neutrophil or complement depletion procedures to prevent the appearance of osmotically fragile RBC and the release of hemoglobin. These data may be relevant to the complications of hemoglobinemia and hemoglobinuria accompanying thermal injury in humans.
Outcomes of Contact Investigations of Infectious Tuberculosis Patients
Authors: SUZANNE M. MARKS, ZACHARY TAYLOR, NOREEN L. QUALLS, ROBIN J. SHRESTHA-KUWAHARA, MAUREEN A. WILCE, CRISTY H. NGUYEN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The objective of this study was to describe outcomes of tuberculosis (TB) contact investigations, factors correlated with those outcomes, and current successes and ways to improve TB contact investigations. We abstracted clinic records of a representative U.S. urban sample of 1,080 pulmonary, sputum-smear( + ) TB patients reported to CDC July 1996 through June 1997 and the cohort of their 6,225 close contacts. We found a median of four close contacts per patient. Fewer contacts were identified for homeless patients. A visit to the patient's residence resulted in two additional (especially child) contacts identified. Eighty-eight percent of eligible contacts received tuberculin skin tests (TSTs). Recording the last exposure date to the infectious patient facilitated follow-up TST provision. Thirty-six percent of contacts were TST( + ). Household contacts and contacts to highly smear( + ) or cavitary TB patients were most likely to be TST( + ). Seventy-four percent of TST( + ) contacts started treatment for latent TB infection (LTBI), of whom 56% completed. Sites using public health nurses (PHNs) started more high-risk TST( − ) contacts on presumptive treatment for LTBI. Using directly observed treatment (DOT) increased the likelihood of treatment completion. We documented outcomes of contact investigation efforts by urban TB programs. We identified several successful practices, as well as suggestions for improvements, that will help TB programs target policies and procedures to enhance contact investigation effectiveness.
International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress
Authors: D. F. Woodward, R. L. Jones, S. Narumiya
Journal: Pharmacological Reviews (2011)

It is now more than 15 years since the molecular structures of the major prostanoid receptors were elucidated. Since then, substantial progress has been achieved with respect to distribution and function, signal transduction mechanisms, and the design of agonists and antagonists (http://www.iuphar-db.org/DATABASE/FamilyIntroductionForward?familyId=58). This review systematically details these advances. More recent developments in prostanoid receptor research are included. The DP(2) receptor, also termed CRTH2, has little structural resemblance to DP(1) and other receptors described in the original prostanoid receptor classification. DP(2) receptors are more closely related to chemoattractant receptors. Prostanoid receptors have also been found to heterodimerize with other prostanoid receptor subtypes and nonprostanoids. This may extend signal transduction pathways and create new ligand recognition sites: prostacyclin/thromboxane A(2) heterodimeric receptors for 8-epi-prostaglandin E(2), wild-type/alternative (alt4) heterodimers for the prostaglandin FP receptor for bimatoprost and the prostamides. It is anticipated that the 15 years of research progress described herein will lead to novel therapeutic entities.
Vascular expression of polycystin.
Authors: Vicente E Torres, Yiquiang Cai, X I Chen, Guanquing Q Wu, Lin Geng, Kathleen A Cleghorn, Christopher M Johnson, Stefan Somlo
Journal: Journal of the American Society of Nephrology (1997)

Autosomal dominant polycystic kidney disease (AD-PKD) is predominantly caused by mutations of the gene PKD1, which encodes a large protein, polycystin, of unknown function. A variety of arterial abnormalities occur with increased prevalence in ADPKD patients. Using an antiserum against the nonduplicated region of the polycystin protein, immunostaining of vascular smooth muscle cells was detected in normal adult elastic arteries. Partial digestion of tissue slices with nonspecific proteases greatly enhanced this staining. Similar enhancement was seen with specific elastase digestion. Immunostaining for smooth muscle actin was not affected by elastase. Antiserum preadsorbed with peptide antigen gave no staining. In specimens of intracranial aneurysms, aortic dissections, and dolichoectatic arteries from thirteen patients with ADPKD, immunostaining of variable intensity for polycystin was demonstrated in arterial smooth muscle cells and myofibroblasts, along with disruption of elastic laminae. Further elastase digestion did not significantly alter staining patterns. Intracranial aneurysms from patients without ADPKD also showed a variable degree of immunostaining with polycystin antisera in the same distribution. The expression of polycystin in arterial smooth muscle suggests a direct pathogenic role for ADPKD-related mutations in the arterial complications of this disease.
Antibiotic Treatment Decreases Microbial Burden Associated with Pseudomyxoma Peritonei and Affects β-Catenin Distribution
Authors: Cristina Semino-Mora, Traci L. Testerman, Hui Liu, Jeannette M. Whitmire, Kimberley Studeman, Yali Jia, Thomas J. McAvoy, Jennifer Francis, Carol Nieroda, Armando Sardi, D. Scott Merrell, Andre Dubois
Journal: Clinical Cancer Research (2013)

Pseudomyxoma peritonei is an understudied cancer in which an appendiceal neoplasm invades the peritoneum and forms tumor foci on abdominal organs. Previous studies have shown that bacteria reside within pseudomyxoma peritonei tumors and mucin. Thus, we sought to analyze the effect of antibiotics on bacterial density and β-catenin expression within pseudomyxoma peritonei samples.The study included 48 patients: 19 with disseminated peritoneal adenomucinosis (DPAM) and 29 with peritoneal mucinous carcinomatosis (PMCA). Fourteen patients were given antibiotics (30 mg lansoprazole, 1 g amoxicillin, and 500 mg clarithromycin) twice a day for 14 days. One week after completion of therapy, surgery was conducted and specimens were harvested for pathology, bacterial culture, ISH, and immunohistochemistry.ISH showed the presence of bacteria in 83% of the patient samples, with a higher Helicobacter pylori density observed in PMCA versus DPAM. PMCA patients treated with antibiotics had a significantly lower bacterial density and decreased β-catenin levels in the cytoplasm, the cell nuclei, and mucin-associated cells. Although not significant, similar trends were observed in DPAM patients. Cell membrane β-catenin was significantly increased in both DPAM and PMCA patients receiving antibiotics.Bacteria play an important role in pseudomyxoma peritonei. Antibiotic treatment improved the histopathology of tissue, particularly in PMCA patients. In PMCA, antibiotics decreased bacterial density and were associated with a significant β-catenin decrease in the cytoplasm, cell nuclei, and mucin along with a small membrane increase. These results suggest that antibiotics offer potential protection against cell detachment, cellular invasion, and metastasis.
<i>mdr-1</i> Single Nucleotide Polymorphisms in Ovarian Cancer Tissue: G2677T/A Correlates with Response to Paclitaxel Chemotherapy
Authors: Henrik Gréen, Peter Söderkvist, Per Rosenberg, György Horvath, Curt Peterson
Journal: Clinical Cancer Research (2006)

Abstract Purpose: P-glycoprotein, encoded by the mdr-1 gene, confers multidrug resistance to a variety of antineoplastic agents, e.g., paclitaxel. Recently, different polymorphisms in the mdr-1 gene have been identified and their consequences for the function of P-glycoprotein, as well as for the treatment response to P-glycoprotein substrates, are being clarified. We analyzed the allelic frequencies at polymorphic sites G2677T/A and C3435T in ovarian cancer patients with good or poor response to treatment with paclitaxel in combination with carboplatin in order to evaluate their predictive values. Experimental Design: Fifty-three patients were included in the study; 28 of them had been relapse-free for at least 1 year and 25 had progressive disease or relapsed within 12 months. A reference material consisting of 200 individuals was also analyzed. The genotypes of each single nucleotide polymorphism (SNP) were determined using Pyrosequencing. Results: The G2677T/A SNP was found to significantly correlate with treatment outcome. The probability of responding to paclitaxel treatment was higher in homozygously mutated patients (T/T or T/A; Fisher's exact test; P &amp;lt; 0.05). The frequency of the T or A alleles was also higher in the group of patients who had a good response (P &amp;lt; 0.05). There was also a dose-dependent influence of the number of mutated alleles on the response to paclitaxel treatment (χ2 test for linear-by-linear association; P = 0.03). However, the C3435T SNP was not found to correlate to treatment outcome. Conclusions: The mdr-1 polymorphism G2677T/A in exon 21 correlates with the paclitaxel response in ovarian cancer and may be important for the function of P-glycoprotein and resistance to paclitaxel and provide useful information for individualized therapy.
A COL4A3 gene mutation and post-transplant anti-α3(IV) collagen alloantibodies in Alport syndrome
Authors: Raghu Kalluri, L.P. van den Heuvel, H.J.M. Smeets, C.H. Schroder, H.H. Lemmink, Ariel Boutaud, Eric G. Neilson, Billy G. Hudson
Journal: Kidney International (1995)

The X-linked Alport syndrome is associated with mutations and deletions in COL4A5 gene, one of six genes which constitute the alpha-chains of type IV collagen in basement membranes. The autosomal recessive form of Alport syndrome is characterized by mutations and deletions in the COL4A3 and COL4A4 genes. A fraction of Alport patients who undergo renal transplantation develop anti-glomerular basement membrane (GBM) nephritis, which results in loss of the renal allograft function. Recently, the target for alloantibodies from an X-linked Alport patient with complete COL4A5 gene deletion was determined to be the alpha 3 chain of type IV collagen. The present study characterized the post-transplant alloantibodies from an autosomal recessive Alport patient with anti-GBM glomerulonephritis and a COL4A3 gene mutation which predicted a loss of 85% of the alpha 3(IV) NC1 domain. The specificity of these new antibodies were studied using glomerular basement membrane constituents and recombinant type IV collagen domains. The results establish the target for the alloantibodies from an autosomal recessive Alport patient with COL4A3 deletion as principally the alpha 3(IV) collagen chain, similar to the post-transplant alloantibodies from X-linked Alport patients with COL4A5 gene deletions. The absence of alpha 3(IV) chain in the GBM of patients with both these forms of Alport syndrome, due either to a failure of synthesis or a failure of assembly, presumably leads to a loss of immunologic tolerance for the alpha 3(IV) NC1 domain in transplanted allografts.
Reliability of the elastic and mechanical properties of esophageal balloon catheters
Authors: Stephan Walterspacher, Lilly Isaak, Josef Gutmann, Hans-Joachim Kabitz, Stefan Schumann
Journal: European Respiratory Journal (2013)

Introduction   Assessment of esophageal pressures via balloon catheters is indispensable for examining the (patho)physiology of the respiratory system. Balloon design, length and filling volumes influence pressure transduction; however the elastic and mechanical properties are unknown in commercially available catheters.   Methods   Six catheters were investigated in four conditions:  a) Measurement of balloon pressure during initial inflations  b) Measurement of static pressures at different filling volumes  c) Compliance estimation in physical models (27, 54, 90 ml/cmH 2 O) at different levels of superimposed pressure  d) Elastic properties following 16 hours of inflation.  Double balloon catheters: Bosch, Germany; nSpire, Germany; NutriVent, Italy  Single balloon catheters: CooperSurgical, USA; VIASYS, USA (8 FR and 16 FR)   Results   a) At the initial inflation most catheters showed pressure artifacts  b) Static pressure measurements were performed with an error  2 O when the balloon was filled according to their unique pressure-volume curve; overfilling resulted in errors >1 cmH 2 O in two balloons (nSpire)  c) The model’s compliance was slightly higher than targeted. Compliance estimations resulted in errors of  2 O compared to direct measurements. Superimposed pressures had no effect on compliance estimation  d) After 16 h of inflation all catheters showed a right shifted pressure-volume curve   Conclusions   Initial inflations and adequate balloon filling prior measurements are crucial for reliable pressure transduction in all catheters. The reliability of pressure measurements and also of compliance estimation via the tested catheters is high. Long-time inflation results in a right-shifted pressure-volume curve.
Multiscale Computational Models of Complex Biological Systems
Authors: Joseph Walpole, Jason A. Papin, Shayn M. Peirce
Journal: Annual Review of Biomedical Engineering (2013)

Integration of data across spatial, temporal, and functional scales is a primary focus of biomedical engineering efforts. The advent of powerful computing platforms, coupled with quantitative data from high-throughput experimental methodologies, has allowed multiscale modeling to expand as a means to more comprehensively investigate biological phenomena in experimentally relevant ways. This review aims to highlight recently published multiscale models of biological systems, using their successes to propose the best practices for future model development. We demonstrate that coupling continuous and discrete systems best captures biological information across spatial scales by selecting modeling techniques that are suited to the task. Further, we suggest how to leverage these multiscale models to gain insight into biological systems using quantitative biomedical engineering methods to analyze data in nonintuitive ways. These topics are discussed with a focus on the future of the field, current challenges encountered, and opportunities yet to be realized.
Collagen proline hydroxylase activity and 35S sulphate uptake in human liver biopsies
Authors: J. OD. McGee, R. S. Patrick, M. C. Rodger, C. M. Luty
Journal: Gut (1974)

In an effort to assess connective tissue biosynthetic activity in human liver disease, collagen proline hydroxylase (a key enzyme in collagen biosynthesis) and the uptake of <sup>35</sup>S sulphate (a precursor of sulphated mucopolysaccharides) were measured in hepatic tissue obtained mainly by percutaneous biopsy. A procedure is described for the quantitation of collagen proline hydroxylase in cryostat sections which allows for the simultaneous histopathological examination of the liver specimen. A three to eightfold increase in the activity of this enzyme was found in four cirrhotic livers compared with the mean value of four normal livers and two biopsies from patients with Gilbert9s syndrome. Elevated hydroxylase levels were found also in five patients with hepatic dysfunction but without cirrhosis (four alcoholics and one patient with persistent hepatitis associated with serum smooth muscle antibody). It is suggested that the hepatic level of collagen proline hydroxylase may be a useful quantitative index of fibroblastic activity in human liver disease. Autoradiographic studies of radioactive sulphate uptake in biopsy specimens from patients with chronic liver disease showed an exaggerated incorporation of isotope not only at sites of established fibrogenesis but also in the walls of sinusoids throughout the liver.
P151 Reduced mortality with blockers when added to stepwise therapy for COPD
Authors: P. M. Short, S. I. W. Lipworth, D. H. Elder, S. Schembri, B. J. Lipworth
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> We wished to examine if β blockers reduced mortality in addition to stepwise therapy for COPD, independent of cardiovascular disease. <h3>Methods</h3> We searched data provided by the Information Services Division of NHS Scotland, to identify patients in NHS Tayside, who required a hospital admission due to COPD. We then searched the NHS Tayside Respiratory Disease Information System (TARDIS) to identify patients since January 2001 to January 2010 who had a documented history of COPD: to collect data on lung function, smoking history and SaO2. We collected prescription data from the Tayside Community Prescription database and history of death in our population from the General Register Office. We also collected history of diabetes and admission to hospital due to cardiovascular disease in our cohort. Using Cox Regression Survival analysis, we calculated the hazard ratios for mortality based upon step wise inhaled therapy and β-blocker use. Cardiovascular and respiratory hospital admissions, diabetes, smoking, age at diagnosis, cardiac drug use, FEV1% and SaO2 were also included in our model. <h3>Results</h3> 27 170 patients were initially identified with a hospital admission due to COPD. 6394 patients were identified through the TARDIS database of which 5977 patients were over 50 years of age and used for analysis. Mean age at diagnosis was 69 years. Mean FEV1% was 62%. 89% of beta-blockers (BB) were cardioselective. All patients were receiving SABA ± ipratropium. Adjusted hazard ratios for mortality and 95% CI9s relative to the control group (mean FEV<sub>1</sub> 71%) receiving SABA ± ipratropium only (n=915) are displayed in the Abstract P151 Table 1. <h3>Conclusion</h3> β Blockers reduce mortality in an additive fashion to stepwise therapy for COPD, independently of cardiac hospital admissions and medications.
Colony-Stimulating Factor-1 Blockade by Antisense Oligonucleotides and Small Interfering RNAs Suppresses Growth of Human Mammary Tumor Xenografts in Mice
Authors: Seyedhossein Aharinejad, Patrick Paulus, Mouldy Sioud, Michael Hofmann, Karin Zins, Romana Schäfer, E. Richard Stanley, Dietmar Abraham
Journal: Cancer Research (2004)

Abstract Colony-stimulating factor (CSF)-1 is the primary regulator of tissue macrophage production. CSF-1 expression is correlated with poor prognosis in breast cancer and is believed to enhance mammary tumor progression and metastasis through the recruitment and regulation of tumor-associated macrophages. Macrophages produce matrix metalloproteases (MMPs) and vascular endothelial growth factor, which are crucial for tumor invasion and angiogenesis. Given the important role of CSF-1, we hypothesized that blockade of CSF-1 or the CSF-1 receptor (the product of the c-fms proto-oncogene) would suppress macrophage infiltration and mammary tumor growth. Human MCF-7 mammary carcinoma cell xenografts in mice were treated with either mouse CSF-1 antisense oligonucleotide for 2 weeks or five intratumoral injections of either CSF-1 small interfering RNAs or c-fms small interfering RNAs. These treatments suppressed mammary tumor growth by 50%, 45%, and 40%, respectively, and selectively down-regulated target protein expression in tumor lysates. Host macrophage infiltration; host MMP-12, MMP-2, and vascular endothelial growth factor A expression; and endothelial cell proliferation within tumors of treated mice were decreased compared with tumors in control mice. In addition, mouse survival significantly increased after CSF-1 blockade. These studies demonstrate that CSF-1 and CSF-1 receptor are potential therapeutic targets for the treatment of mammary cancer.
Focal reduction of villous blood flow in early indomethacin enteropathy: a dynamic vascular study in the rat
Authors: D A Kelly, C Piasecki, A Anthony, A P Dhillon, R E Pounder, A J Wakefield
Journal: Gut (1998)

Background —Oral indomethacin causes villous shortening, microvascular damage, and distortion, which might induce mucosal ischaemia and necrosis. Aims —In order to determine the early events in indomethacin induced jejunal injury we examined the temporal relations between morphological damage and changes in villous blood flow following indomethacin. Methods —In anaesthetised rats, mid jejunal villi were exteriorised in a chamber and observed by fluorescence microscopy. Blood flow in surface capillaries was calculated from velocities and diameters. Indomethacin was applied by both luminal and intravenous routes for 90 minutes, after which the animal was perfusion fixed and the villi were processed for histological examination. Control animals received intravenous or luminal bicarbonate (1.25%). Results —Blood flow slowed in individual villi at 20 minutes, and progressed to complete stasis (in another group) by 45 minutes. Histological examination at 20 minutes revealed microvascular distortion, but no villous shortening: crypt depth:villous height ratios were 0.356 (0.02) in test and 0.386 (0.01) in surrounding villi (p&gt;0.5). At stasis, the villi under study showed epithelial clumping and were shortened: crypt depth:villous height ratios were 0.92 (0.2) in test and 0.42 (0.06) in surrounding villi (p&lt;0.02). Vehicle alone had no effect on either blood flow or histology. Conclusions —Focal slowing of villous blood flow and microvascular distortion precede villus shortening and epithelial disruption, and indicate that damage to surface microvasculature is an early event in indomethacin induced mucosal injury in this model.
The Effect of Glatiramer Acetate Therapy on Functional Properties of B Cells From Patients With Relapsing-Remitting Multiple Sclerosis
Authors: Sara J. Ireland, Alyssa A. Guzman, Dina E. O’Brien, Samuel Hughes, Benjamin Greenberg, Angela Flores, Donna Graves, Gina Remington, Elliot M. Frohman, Laurie S. Davis, Nancy L. Monson
Journal: JAMA Neurology (2014)

This study describes what is, to our knowledge, the previously unknown effect of glatiramer acetate therapy on B cells in patients with relapsing-remitting multiple sclerosis (MS).To determine whether glatiramer acetate therapy normalizes dysregulated B-cell proliferation and cytokine production in patients with MS.Twenty-two patients with MS who were receiving glatiramer acetate therapy and 22 treatment-naive patients with MS were recruited at The University of Texas Southwestern Medical Center MS clinic. Cell samples from healthy donors were obtained from HemaCare (Van Nuys, California) or Carter Blood Bank (Dallas, Texas). Treatment-naive patients with MS had not received any disease-modifying therapies for at least 3 months before the study.Glatiramer acetate therapy for at least 3 months at the time of the study.B-cell phenotype and proliferation and immunoglobulin and cytokine secretion.A restoration of interleukin 10 production by peripheral B cells was observed in patients undergoing glatiramer acetate therapy as well as a significant reduction of interleukin 6 production in a subset of patients who received therapy for less than 32 months. Furthermore, proliferation in response to high-dose CD40L was altered and immunoglobulin production was elevated in in vitro-activated B cells obtained from patients who received glatiramer acetate.Glatiramer acetate therapy remodels the composition of the B-cell compartment and influences cytokine secretion and immunoglobulin production. These data suggest that glatiramer acetate therapy affects several aspects of dysregulated B-cell function in MS that may contribute to the therapeutic mechanisms of glatiramer acetate.