tbuckley/cabot-search huggingface dataset:
THE INCIDENCE OF INFECTION AMONG CONTACTS OF POLIOMYELITIS CASES 1
Authors: Dorothy M. Horstmann, Robert W. McCollum, Anne D. Mascola
Journal: Journal of Clinical Investigation (1955)

One of the epidemiological features which puzzled early students of poliomyelitis was the apparently erratic spread of the disease with rarely more than one case in a family. Subsequently, it became apparent that unlike measles among the common virus diseases, the majority of infections with poliomyelitis virus were either mild or inapparent and, therefore, went undetected. A number of epidemiological survey studies carried out during the past two decades indicated that actually a high infection rate was common among family contacts of poliomyelitis cases even though only one individual in the family became sick. Until recently, however, the laboratory methods available for studying the problem were largely limited to the isolation of virus by monkey inoculation, and the exact rates or degree of spread of this infection through families remained unknown. With the introduction of tissue culture methods into poliomyelitis research, it has been possible to carry out more extensive virological studies, and to relate virus isolation-or its absence-to the immune or antibody status of the individuals tested. The present study is concerned with poliomyelitis infection rates among close contacts of cases and indicates actually how high they may be. Tissue culture methods, which have been brought to bear on the problem, have been responsible for these results.
CD8+ T cell concentration determines their efficiency in killing cognate antigen–expressing syngeneic mammalian cells in vitro and in mouse tissues
Authors: Sadna Budhu, John D. Loike, Ashley Pandolfi, Soo Han, Geoffrey Catalano, Andrei Constantinescu, Raphael Clynes, Samuel C. Silverstein
Journal: The Journal of Experimental Medicine (2010)

We describe a quantitative model for assessing the cytolytic activity of antigen-specific CD8+ T cells in vitro and in vivo in which the concentration of antigen-specific CD8+ T cells determines the efficiency with which these cells kill cognate antigen-expressing melanoma cells in packed cell pellets, in three-dimensional collagen-fibrin gels in vitro, and in established melanomas in vivo. In combination with a clonogenic assay for melanoma cells, collagen-fibrin gels are 4,500-5,500-fold more sensitive than the packed cell pellet-type assays generally used to measure CD8+ T cell cytolytic activity. An equation previously used to describe neutrophil bactericidal activity in vitro and in vivo also describes antigen-specific CD8+ T cell-mediated cytolysis of cognate antigen-expressing melanoma cells in collagen-fibrin gels in vitro and in transplanted tumors in vivo. We have used this equation to calculate the critical concentration of antigen-specific CD8+ T cells, which is the concentration of these cells required to hold constant the concentration of a growing population of cognate antigen-expressing melanoma cells. It is approximately 3.5x10(5)/ml collagen-fibrin gel in vitro and approximately 3x10(6)/ml or /g melanoma for previously published studies of ex vivo-activated adoptively transferred tumor antigen-specific CD8+ T cell killing of cognate antigen-expressing melanoma cells in established tumors in vivo. The antigen-specific CD8+ T cell concentration required to kill 100% of 2x10(7)/ml cognate antigen-expressing melanoma cells in collagen fibrin gels is >or=10(7)/ml of gel.
The Ehlers-Danlos syndrome: an analysis of the structure of the collagen fibres of the skin
Authors: CAROL M. BLACK, L. J. GATHERCOLE, A. J. BAILEY, P. BEIGHTON
Journal: British Journal of Dermatology (1980)

The structure of the collagen fibres of the skin in the Ehlers-Danlos syndrome (ED-S) was studied in eight patients with ED-S Type I, three patients with ED-S Type II and three patients with the X-linked Type V. The results show that the reducible cross-links are present and undergo the same maturation process to non-reducible cross-links as in normal skin. Transmission electron microscopy revealed a normal ultrastructure of the collagen fibrils. At a higher morphological level of organization scanning electron microscopy demonstrated progressive increase in fibre bundle disorder from the X-linked to mitis, to gravis, in which the fibres making up the large fibre bundles demonstrated a considerable inability to aggregate.
P2-13-07: Prevalence of Germline BRCA1 and BRCA2 Deleterious Mutations in Brazilian Patients with High-Risk of Breast and Ovarian Cancer.
Authors: MDPE Diz, KA Escobar, RSC Guindalini, FS Pasini, ML Snitkoviski, S Maistro, PMG Hoff, MHH Federico
Journal: Cancer Research (2011)

Abstract Background: Germline mutations in the BRCA1/2 genes account for the majority of hereditary breast ovarian cancer (HBOC). Distribution and prevalence of clinically relevant mutations in BRCA1/2 differ among different populations. All of the Brazilian studies published to date have not performed complete sequencing of both genes, restricting their analyses to selected exons. In addition, a highly heterogeneous mutation spectrum was observed. The lack of data concerning the prevalence and profile of BRCA1/2 deleterious mutation and the appropriated screening criteria for DNA sequencing in the Brazilian population complicates the design of screening strategies. Objective: To accurately determine the contribution of BRCA1/2 germline mutations in a well characterized sample of Brazilian breast and ovarian high-risk pts. Methodology: A total of 73 unrelated pts attending a Brazilian public hospital from September 2005 to July 2006, with HBOC risk ≥10% according to Frank, Evans or BRCAPRO algorithms, underwent complete sequencing and MLPA analysis of BRCA1/2 genes. Demographic data and tumor pathological features were extracted from prospectively registered medical records. Results: Mean age, median of cancer cases in families and median score by Frank, Evans and BRCAPRO algorithms were respectively 48y (24-78), 4 (0-13), 11.2 (0-56,3), 13.4 (0,1-100) and 16 (2-75). A total of 79 unknown clinical significance mutations were identified: 44 in BRCA1 and 35 in BRCA2. Known deleterious mutations were identified in 8 pts. Four in BRCA1: R71G at exon 5, 5382insC at exon 20 (2 patients) and R1751X at exon 20; and four in BRCA2: R2318X at exon 13, R3128X at exon 25, 5844del5 and 6633del5 at exon 11. Several polymorphisms were found in all pts. No mutation was detected by MLPA technique. One novel frameshift deleterious mutation in BRCA2: 6610insTT at exon 11 which results in a stop codon was detected in a breast cancer patient and in four of her relatives from a family with high-risk of HBOC. Taking into account the novel mutation, the prevalence of BRCA1/2 mutation in high-risk pts in our cohort is 12,3%. Pts characteristics presented in [table 1]. Conclusion: To the best of our knowledge, the study represents the first report of the complete sequencing and MLPA analysis of BRCA1/2 genes in large Brazilian series of HBOC high-risk pts. The prevalence of germline mutations found in the present study was similar to the reported by other studies examining high-risk populations. B1=BRCA1; B2=BRCA2; BC=breast cancer; IDC=invasive ductal carcinoma; MC=medullary carcinoma; ILC=invasive lobular carcinoma; HR=hormone receptor; (b)=bilateral, N/A=not available; N/C=never had cancer; pos=positive; neg=negative, ind=indeterminate Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-07.
Decreased lung function in one year survivors of allogeneic bone marrow transplantation conditioned with high-dose busulphan and cyclophosphamide
Authors: MB Lund, J Kongerud, L Brinch, SA Evensen, J Boe
Journal: European Respiratory Journal (1995)

Conditioning with busulphan (BU) and cyclophosphamide (CY) prior to allogeneic bone marrow transplantation (BMT) is an alternative to regimens that include total body irradiation (TBI). The aim of the study was to assess the occurrence and degree of lung function impairment after this treatment. Prospectively, 43 consecutive patients, aged 17-51 (median 31) yrs, were examined by lung function measurements and clinical and radiographic evaluation, prior to BMT and at 3 month intervals up to 1 yr after BMT. All patients had normal chest radiographs before BMT and at the 12 month follow-up. Mean baseline values were above 100% of predicted normal for lung volumes and above 90% for gas transfer. Excluded from the lung function follow-up analyses were nine patients who had suffered infectious pneumonia and/or developed obliterative bronchiolitis. For the remaining patients (n = 34), mean alveolar volume (VA), forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) had dropped by nearly 10% compared with baseline 3 months after BMT, but were restored within 1 yr. FEV1/FVC x 100 (FEV1%) was increased, reflecting the restrictive pattern. Hb-adjusted transfer factor of the lungs for carbon monoxide (TL,CO) had dropped by 20% after 3 months, and remained reduced by 15% after 1 year. Prior to BMT the smokers had significantly lower TL,CO than the nonsmokers, and after BMT the difference was accentuated. Reductions in lung function were independent of sex, age and type of haematological disorder. We conclude that BMT with BU/CY is associated with transient declines in lung volumes and a persistent reduction in gas transfer 1 yr after therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Evidence of a role for matrix metalloproteinases in cold preservation injury of the liver in humans and in the rat
Authors: A G Upadhya, R P Harvey, T K Howard, J A Lowell, S Shenoy, S M Strasberg
Journal: Hepatology (1997)

Previous studies have determined that proteases are important in cold preservation injury to the liver. The purpose of this study was to determine the role of matrix metalloproteinases (MMPs) in cold preservation injury. Effluents were collected from rat livers after various periods of preservation either in Eurocollins solution or in University of Wisconsin (UW) solution. Effluents were also collected from 17 human donor livers stored in UW solution. To determine whether sinusoidal endothelial cells released MMPs when placed in the cold, these cells were isolated from rat livers and cultured at 4 degrees C. Gelatin zymography, quantitative assay of gelatinolytic activity, immunoprecipitation, and Western blotting were used to identify metalloproteinases and to measure their activity. Human and rat liver effluents contained gelatin-digesting bands on zymography. Their appearance was inhibited by specific metalloproteinase inhibitors and also by lactobionate, the major ingredient of UW solution. The most prominent bands in humans and the rat appeared at approximately 72 kd and 92 kd, suggesting that they were the MMPs 72-kd gelatinase and 92-kd gelatinase. Supernatants of isolated rat sinusoidal endothelial cells stored in the cold contained similar bands. In the rat, the proteinases were present in both latent and active forms, but, in humans, predominately the latent form was seen. In humans, there were four prominent bands in the gelatin zymography. By immunoprecipitation, two of the bands were identified as the 92-kd gelatinase and a dimer or polymer of 92-kd gelatinase. Using Western blotting with a monoclonal antibody, a third band was identified as 72-kd gelatinase. In quantitative terms, gelatinolytic activity increased with time of cold storage in humans and in the rat. In the rat, gelatinolytic activity was greater when Eurocollins was the preservative than when UW solution was used. Taken together, these results indicate an important role for MMPs in the injury produced by cold preservation of the liver.
Visual Assessment Versus Quantitative Three-Dimensional Stereotactic Surface Projection Fluorodeoxyglucose Positron Emission Tomography for Detection of Mild Cognitive Impairment and Alzheimer Disease
Authors: Vance T. Lehman, Rickey E. Carter, Daniel O. Claassen, Robert C. Murphy, Val Lowe, Ronald C. Petersen, Patrick J. Peller
Journal: Clinical Nuclear Medicine (2012)

Introduction We examined the clinical impact of commercially available quantitation software using 3-dimensional stereotactic surface projection (3D-SSP) on the diagnostic accuracy of 18F fluorodeoxyglucose positron emission tomography (18F FDG PET) in mild cognitive impairment (MCI) and Alzheimer disease (AD). Methods Enrollees underwent clinical evaluation to determine cognitive status and subsequent 18F FDG PET neuroimaging. Four blinded readers (2 novices and 2 experts) rated the images for degree of abnormality and interpretive confidence without and with 3D-SSP. Diagnostic accuracy was determined with area under the curve (area under the curve) of a receiver operating characteristic (receiver operating characteristic) curve analysis and change in confidence with model-based means (LSMeans). Results Twenty-three normal controls and 31 patients with cognitive impairment (18 MCI and 13 AD) were enrolled (28 female and 26 male; mean age 74 years). During follow-up (mean 3.6 years), all normal participants remained normal, 12 of 18 participants with MCI progressed to dementia, and all participants with baseline dementia progressed. The area under the curve with 3D-SSP (0.88; 95% CI: 0.76–0.95) was significantly higher than without it (0.72; 95% CI: 0.55–0.83). The specificity increased from 26% to 63% for novices and from 56% to 87% for experts with addition of 3D-SSP, whereas the sensitivity was essentially unchanged at 86% and 86% for the beginners and 81% and 79% for the experts. The interpretive confidence increased significantly from 3.3 to 4.0 (maximum value = 5, P = 0.048). Conclusion The use of commercially available 3D-SSP quantitation improved diagnostic accuracy for evaluation of MCI and AD with 18F FDG PET.
Characterization of Tumor Infiltrating Lymphocytes in Human Breast Cancer by Infrared Imaging
Authors: M. Verdonck, S. Garaud, L. Buisseret, H. Duvillier, C. Desmedt, R. de Wind, C. Sotiriou, K. Willard-Gallo, E. Goormaghtigh
Journal: Annals of Oncology (2014)
High-Level, β-Catenin/TCF-Dependent Transgene Expression in Secondary Colorectal Cancer Tissue
Authors: Kai S. Lipinski, A.Hakim Djeha, Tariq Ismail, Andrew Mountain, Lawrence S. Young, Christopher J. Wrighton
Journal: Molecular Therapy (2001)

There is an urgent need for improved therapies for inoperable metastatic colon cancer. Gene-directed enzyme prodrug therapy (GDEPT) using adenovirus vectors works well in preclinical models of this disease, but successful clinical application is hampered by an inability to construct vectors that express at high levels in infected tumor cells but not in infected normal cells. Constitutive activation of beta-catenin-dependent gene expression is almost certainly a key causative event in the genesis of colon and some other cancers. Here we have exploited this oncogenic defect to design a synthetic promoter, CTP1, that, in contrast to currently available tumor-selective promoters, is both highly active in cancer cells and highly cancer-cell-specific. CTP1 directs high-level beta-galactosidase expression in freshly isolated biopsies of secondary colon cancer, but is not detectably active in associated normal liver tissue. We also demonstrate that CTP1 can direct high-level, tumor-specific therapeutic gene expression in vivo. Intratumoral injection of an adenovirus vector encoding Escherichia coli nitroreductase driven by CTP1 efficiently sensitized SW480 xenografts to the prodrug CB1954, whereas systemic vector and prodrug administration produced no apparent signs of toxicity. CTP1 may form the basis for effective, targeted gene therapy of metastatic colon cancer and other tumors with deregulated beta-catenin/T cell factor.
Abstract 1107: β2-integrin-derived signals induce cell survival and proliferation of AML blasts by activating a Syk/STAT signaling axis.
Authors: Thomas Oellerich, Mark Oellerich, Michael Engelke, Silvia Muench, Sebastian Mohr, He-Hsuan Hsiao, Jing Zhang, Hanibal Bohnenberger, Tobias Berg, Michael Rieger, Juergen Wienands, Gesine Bug, Christian Brandts, Henning Urlaub, Hubert Serve
Journal: Cancer Research (2013)

Abstract Constitutive activation of certain kinase-dependent signal transduction pathways is critical for the pathogenesis of acute myeloid leukemia (AML). Apart from FLT3-ITD the spleen tyrosine kinase (Syk) induces cell survival and proliferation in a high proportion of AML blasts, but the underlying molecular events of Syk signaling have not been investigated so far. Using a phosphoproteomic approach we elucidated the AML-specific phosphorylation state of Syk and found that the kinase is constitutively phosphorylated at all known activation inducing tyrosine residues. Moreover, we have identified the multi-protein complex that is nucleated by constitutively active Syk in AML cells by quantitative proteomic techniques. This complex differs from the B lymphoid Syk interactome regarding several proteins, in particular the β2-integrin receptor Mac-1 and also the oncogenic transcription factors STAT3 and STAT5. Our functional studies in primary AML cell cultures revealed that tonic signals derived from the integrin-associated Fc-γ chain lead to Syk-dependent activation of STAT3 and STAT5 that in turn induces AML cell proliferation. Moreover, stimulation of Mac-1 intensifies the constitutive Syk-mediated STAT3/5 activation in AML cells, a scenario likely to take place in the bone marrow niche. In accordance with these findings, we observed that β2-integrins including Mac-1 induce proliferation of AML cells in an AML cell/stroma co-culture model. Taken together, we identified an oncogenic integrin/Syk/STAT signaling axis that might serve as a therapeutic target of AML in the future. Citation Format: Thomas Oellerich, Mark Oellerich, Michael Engelke, Silvia Muench, Sebastian Mohr, He-Hsuan Hsiao, Jing Zhang, Hanibal Bohnenberger, Tobias Berg, Michael Rieger, Juergen Wienands, Gesine Bug, Christian Brandts, Henning Urlaub, Hubert Serve. β2-integrin-derived signals induce cell survival and proliferation of AML blasts by activating a Syk/STAT signaling axis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1107. doi:10.1158/1538-7445.AM2013-1107
Effects of Elastase, Collagenase, and Papain on Structure and Function of Rat Lungs In Vitro
Authors: Waldemar G. Johanson, Alan K. Pierce
Journal: Journal of Clinical Investigation (1972)

Present concepts of the roles of collagen and elastin in lung elastic behavior and maintenance of lung structure have been largely inferred from anatomical observations or from studies of isolated fibers in vitro. Based on the intimate association of elastin and collagen it has been postulated that elastin contributes little to elastic behavior and that collagen is the major determinant of lung structure. Using clostridial collagenase, pancreatic elastase, and papain we have selectively degraded these fibers and studied the resulting changes in elastic behavior and structure of rat lungs in vitro.Pressure-volume curves were recorded during continuous slow air inflation and deflation (10.5 ml/min) before and after the intratracheal instillation of 0.5 ml of control or enzyme solution. Surface tension-lowering activity of lavaged material was studied. All lungs were fixed inflated at 25 cm H(2)O pressure and whole lung sections were stained for elastin, collagen, and reticulin. Collagenase produced a marked susceptibility to pleural rupture but did not alter elastic behavior or lung structure. Elastase and papain produced segments of lung with increased compliance; this change was not due to alteration in surface forces but was associated with decreased tissue elastic recoil. Histologically, altered tissue recoil correlated well with evidence of damaged elastin fibers. In contrast to previous concepts these results suggest that elastin is the major connective tissue determinant of lung structure and elastic behavior.
Response to Neoadjuvant Chemoradiation in Rectal Cancer: Time to Consider Risk-Adapted Adjuvant Chemotherapy
Authors: Ahmad Al Zahrani, Mahfoudh Mohammed, Luai Ashari, Alaa Abdul Jabbar, Samar Al Homoud, Ali Al Jubran, Hadeel Al Manae, Shouki Bazarbashi, Mohammed Mohuiddin, Nasser Al Sanea
Journal: Annals of Oncology (2013)
Reinstituting warfarin in patients who develop warfarin skin necrosis
Authors: Anand P. Jillella, Charles L. Lutcher
Journal: American Journal of Hematology (1996)

Skin necrosis is a rare but serious complication of oral anticoagulation with coumarin derivatives. Frequently, the necrosis can be extensive and may result in major morbidity and mortality. The majority of these patients require prolonged anticoagulation for life-threatening conditions such as deep various thrombosis and pulmonary embolism. Resuming oral anticoagulants in the face of skin necrosis is a difficult decision for both the patient and the physician. Because long-term heparin therapy is inconvenient and is associated with significant side effects, we reviewed the literature to find alternative treatment strategies. A Medline search was done, and all papers published in English since 1967 were reviewed. Of 58 cases with skin necrosis attributed to oral anticoagulants, oral anticoagulation was resumed in 7 patients with no resulting adverse effects. Warfarin is the most widely used coumarin derivative in the United States. Based on our review, we make recommendations for resuming warfarin in patients who have developed skin necrosis when the clinical condition absolutely requires prolonged anticoagulation.