tbuckley/cabot-search huggingface dataset:
Relation of Alleles of the Collagen Type Iα1 Gene to Bone Density and the Risk of Osteoporotic Fractures in Postmenopausal Women
Authors: André G. Uitterlinden, Huibert Burger, Qiuju Huang, Fang Yue, Fiona E.A. McGuigan, Struan F.A. Grant, Albert Hofman, Johannes P.T.M. van Leeuwen, Huibert A.P. Pols, Stuart H. Ralston
Journal: New England Journal of Medicine (1998)

Osteoporosis is a common disorder with a strong genetic component. One way in which the genetic component could be expressed is through polymorphism of COLIA1, the gene for collagen type Iα1, a bone-matrix protein.
Mallory body-A disease-associated type of sequestosome
Authors: Cornelia Stumptner, Andrea Fuchsbichler, Hans Heid, Kurt Zatloukal, Helmut Denk
Journal: Hepatology (2002)

Mallory bodies (MBs) consist of abnormal keratins, ubiquitin, heat shock proteins, and the protein p62. p62 is encoded by an immediate-early response gene that rapidly responds to a variety of extracellular signals involved in cell proliferation, differentiation, and particularly oxidative stress. It acts as an adapter in signal transduction and binds noncovalently to ubiquitin, possibly being involved in the regulation of the fate of ubiquitinated proteins by segregation ( i.e. , sequestosome or aggresome formation). The presence of p62 together with ubiquitinated abnormal keratins in the MB characterizes MBs as a disease-associated type of sequestosome. A detailed study on the expression of p62 and its relationship to MB formation in the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-treated mouse liver is reported based on immunohistochemical, immunoblot, and Northern blot analyses. The results indicate that p62 is rapidly induced in hepatocytes of intoxicated animals preceding MB formation. As suggested by experiments with short-term DDC-treated naive mice and mice refed DDC after recovery from long-term DDC treatment (primed mice), p62 does not exert an initiating effect on MB formation but the appearance of MBs requires the presence of abnormal keratins, which associate with p62 after ubiquitination. The rapid induction of p62 and its association with MBs further support the role of oxidative stress in MB formation. In conclusion, the constant presence of p62 in MBs suggests that binding of p62 to abnormal keratins may allow hepatocytes to dispose potentially harmful proteins in a biologically inert manner.
Thieme Clinical Companions. Dermatology by Wolfram Sterry, Ralf Paus, and Walter Burgdorf; Derm notes. Dermatology Clinical Pocket Guide by Benjamin Barankin, and Anatoli Freiman; Pocket Guide for Cutaneous Medicine and Surgery by Joshua E. Lane, MD
Authors: John Kawaoka
Journal: Journal of the American Academy of Dermatology (2007)
Hemochromatosis and Iron-Overload Screening in a Racially Diverse Population
Authors: Paul C. Adams, David M. Reboussin, James C. Barton, Christine E. McLaren, John H. Eckfeldt, Gordon D. McLaren, Fitzroy W. Dawkins, Ronald T. Acton, Emily L. Harris, Victor R. Gordeuk, Catherine Leiendecker-Foster, Mark Speechley, Beverly M. Snively, Joan L. Holup, Elizabeth Thomson, Phyliss Sholinsky
Journal: New England Journal of Medicine (2005)

Iron overload and hemochromatosis are common, treatable conditions. HFE genotypes, levels of serum ferritin, transferrin saturation values, and self-reported medical history were studied in a multiethnic primary care population.Participants were recruited from primary care practices and blood-drawing laboratories. Blood samples were tested for transferrin saturation, serum ferritin, and C282Y and H63D mutations of the HFE gene. Before genetic screening, participants were asked whether they had a history of medical conditions related to iron overload.Of the 99,711 participants, 299 were homozygous for the C282Y mutation. The estimated prevalence of C282Y homozygotes was higher in non-Hispanic whites (0.44 percent) than in Native Americans (0.11 percent), Hispanics (0.027 percent), blacks (0.014 percent), Pacific Islanders (0.012 percent), or Asians (0.000039 percent). Among participants who were homozygous for the C282Y mutation but in whom iron overload had not been diagnosed (227 participants), serum ferritin levels were greater than 300 mug per liter in 78 of 89 men (88 percent) and greater than 200 microg per liter in 79 of 138 women (57 percent). Pacific Islanders and Asians had the highest geometric mean levels of serum ferritin and mean transferrin saturation despite having the lowest prevalence of C282Y homozygotes. There were 364 participants in whom iron overload had not been diagnosed (29 C282Y homozygotes) who had a serum ferritin level greater than 1000 microg per liter. Among men, C282Y homozygotes and compound heterozygotes were more likely to report a history of liver disease than were participants without HFE mutations.The C282Y mutation is most common in whites, and most C282Y homozygotes have elevations in serum ferritin levels and transferrin saturation. The C282Y mutation does not account for high mean serum ferritin levels and transferrin saturation values in nonwhites.
Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice
Authors: Elisabeth R. Barton-Davis, Laurence Cordier, Daria I. Shoturma, Stuart E. Leland, H. Lee Sweeney
Journal: Journal of Clinical Investigation (1999)

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene, leading to the absence of the dystrophin protein in striated muscle. A significant number of these mutations are premature stop codons. On the basis of the observation that aminoglycoside treatment can suppress stop codons in cultured cells, we tested the effect of gentamicin on cultured muscle cells from the mdx mouse — an animal model for DMD that possesses a premature stop codon in the dystrophin gene. Exposure of mdx myotubes to gentamicin led to the expression and localization of dystrophin to the cell membrane. We then evaluated the effects of differing dosages of gentamicin on expression and functional protection of the muscles of mdx mice. We identified a treatment regimen that resulted in the presence of dystrophin in the cell membrane in all striated muscles examined and that provided functional protection against muscular injury. To our knowledge, our results are the first to demonstrate that aminoglycosides can suppress stop codons not only in vitro but also in vivo. Furthermore, these results raise the possibility of a novel treatment regimen for muscular dystrophy and other diseases caused by premature stop codon mutations. This treatment could prove effective in up to 15% of patients with DMD.
The clinical impact of nucleic acid amplification tests on the diagnosis and management of tuberculosis in a British hospital
Authors: M Taegtmeyer, N J Beeching, J Scott, K Seddon, S Jamieson, S B Squire, H C Mwandumba, A R O Miller, P D O Davies, C M Parry
Journal: Thorax (2007)

Nucleic acid amplification tests (NAAT) based on PCR provide rapid identification of Mycobacterium tuberculosis and the detection of rifampicin resistance. Indications for their use in clinical samples are now included in British tuberculosis guidelines.A retrospective audit of patients with suspected mycobacterial infection in a Liverpool hospital between 2002 and 2006. Documentation of the impact of NAAT usage in acid fast bacillus (AFB) microscopy positive samples on clinical practice and the influence of a multidisciplinary group on their appropriate use, compared with British guidelines.Mycobacteria were seen or isolated from 282 patients and identified as M tuberculosis in 181 (64%). NAAT were indicated in 87/123 AFB positive samples and performed in 51 (59%). M tuberculosis was confirmed or excluded by this method in 86% of tested samples within 2 weeks, compared with 7% identified using standard methods. The appropriate use of NAAT increased significantly over the study period. The NAAT result had a clinical impact in 20/51 (39%) tested patients. Culture results suggest the potential for a direct clinical impact in 8/36 (22%) patients in which it was indicated but not sent and 5/36 (14%) patients for whom it was not indicated. Patients managed by the multidisciplinary group had a higher rate of HIV testing and appropriate use of NAAT.There were significant clinical benefits from the use of nucleic acid amplification tests in this low prevalence setting. Our data suggest that there would be additional benefit from their use with all AFB smear positive clinical samples.
Pseudomonas Sternotomy Wound Infection and Sternal Osteomyelitis
Authors: H. Grant Stiver
Journal: JAMA (1979)

Pseudomonas aeruginosa sternotomy wound infections occurred in five patients who underwent open heart surgery. The initial isolate in each case was from a mediastinal chest tube routinely cultured on removal. Soft-tissue infection developed in two patients, and sternal osteomyelitis developed in three patients. Pseudomonas-typing studies showed a correlation between five isolates from chest-tube suction pumps used postoperatively and the wound isolates. Analysis of antibiograms of Pseudomonas wound isolates from the cardiac surgery ward from 1975 to 1977 showed eight of 15 with the same antibiogram as the sternotomy pathogens, compared with two of 13 isolates from other wards.
Valve Configuration Determines Long-Term Results After Repair of the Bicuspid Aortic Valve
Authors: Diana Aicher, Takashi Kunihara, Omar Abou Issa, Brigitte Brittner, Stefan Gräber, Hans-Joachim Schäfers
Journal: Circulation (2011)

Reconstruction of the regurgitant bicuspid aortic valve has been performed for >10 years, but there is limited information on long-term results. We analyzed our results to determine the predictors of suboptimal outcome.Between November 1995 and December 2008, 316 patients (age, 49±14 years; male, 268) underwent reconstruction of a regurgitant bicuspid aortic valve. Intraoperative assessment included extent of fusion, root dimensions, circumferential orientation of the 2 normal commissures (>160°, ≤160°), and effective height after repair. Cusp pathology was treated by central plication (n=277), triangular resection (n=138), or pericardial patch (n=94). Root dilatation was treated by subcommissural plication (n=100), root remodeling (n=122), or valve reimplantation (n=2). All patients were followed up echocardiographically (cumulative follow-up, 1253 years; mean, 4±3.1 years). Clinical and morphological parameters were analyzed for correlation with 10-year freedom from reoperation with the Cox proportional hazards model. Hospital mortality was 0.63%; survival was 92% at 10 years. Freedom from reoperation at 5 and 10 years was 88% and 81%; freedom from valve replacement, 95% and 84%. By univariable analysis, statistically significant predictors of reoperation were age (hazard ratio [HR]=0.97), aortoventricular diameter (HR=1.24), effective height (HR=0.76), commissural orientation (HR=0.95), use of a pericardial patch (HR=7.63), no root replacement (HR=3.80), subcommissural plication (HR=2.07), and preoperative aortic regurgitation grade 3 or greater. By multivariable analysis, statistically significant predictors for reoperation were age (HR=0.96), aortoventricular diameter (HR=1.30), effective height (HR=0.74), commissural orientation (HR=0.96), and use of a pericardial patch (HR=5.16).Reconstruction of bicuspid aortic valve can be performed reproducibly with good early results. Recurrence and progression of regurgitation, however, may occur, depending primarily on anatomic features of the valve.
Radiation therapy versus chemotherapy as initial treatmentfor localized nasal natural killer (NK)/T-cell lymphoma:a single institute survey in Taiwan
Authors: J.-Y. You, K.-H. Chi, M.-H. Yang, C.-C. Chen, C.-H. Ho, W.-K. Chau, H.-C. Hsu, J.-P. Gau, C.-H. Tzeng, J.-H. Liu, P.-M. Chen, T.-J. Chiou
Journal: Annals of Oncology (2004)
Comparison of the Level of Cellular Retinoid-Binding Proteins and Susceptibility to Retinoid-Induced Growth Inhibition of Various Neoplastic Cell Lines<xref ref-type="fn" rid="FN2">2</xref>
Authors: R Lotan, D E Ong, F Chytil
Journal: JNCI Journal of the National Cancer Institute (1980)

The presence and level of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) were determined in several neoplastic cell lines. These cells exhibited different degrees of susceptibility to growth inhibition in culture by two retinoids, retinyl acetate and retinoic acid. CRABP was detected in 10 and CRBP in 3 of the 11 tested cell lines. The levels of CRBP and CRABP were in the ranges 15-3,400 and 4-1,290 pmol per 109 cells, respectively, as determined by sucrose gradient centrlfugation. Cell lines that contained CRABP included S91 and B16 melanomas; Mm5mT and DMBA #8 mammary adenocarcinomas; BW5147, BW5147-RicR, and P3 neoplastic lymphoid cells; F361.2 (a hybrid cell line obtained by fusion of MSV3T3 and BW5147); MSV3T3 sarcoma; and RAW8 lymphosarcoma. All but the last two cell lines were inhibited by retlnoic acid in culture. CRBP was detected in extracts of S91, Mm5mT, and RAW8. Retinyl acetate inhibited the growth of all cell lines with the exception of RAW8, MSV3T3, and F361.2. No correlation was found between the level of either binding protein and the extent of growth inhibition by either retinyl acetate or retinoic acid. Neither of the binding proteins was detected in L1210-A5 leukemia cells, whose proliferation can be Inhibited by both retinyl acetate and retinoic acid. These data indicated that screening cell lines for the presence and level of CRBP and CRABP is not sufficient to predict the susceptibility of cultured cells to growth inhibition by retinoids.
Influence of local anesthetics upon human polymorphonuclear leukocyte function in vitro. Reduction of lysosomal enzyme release and superoxide anion production.
Authors: I M Goldstein, S Lind, S Hoffstein, G Weissmann
Journal: The Journal of Experimental Medicine (1977)

Cationic local anesthetics have been reported to influence cellular responses to surface stimuli by interfering with the function of microtubules and microfilaments. Since unimpaired microtubule and microfilament functions are required by human polymorphonuclear leukocytes in order to respond normally to surface stimulation, we have studied effects of the local anesthetic, tetracaine on the function and morphology of these cells in vitro. Tetracaine (0.25--1.0 mM) significantly reduced extracellular release of the lysosomal enzymes, beta-glucuronidase and lysozyme from polymorphonuclear leukocytes exposed to serum-treated zymosan (a particulate stimulus), zymosan-treated serum (a soluble stimulus), and to the surface-active lectin, concanavalin A. Tetracaine also significantly reduced superoixde anion production (superoxide dismutase-inhibitable cytochrome c reduction) by these cells. Tetrancaine was not cytotoxic and its effects could be reversed completely by washing cells once with buffer. Electron microscope examination of tetracaine-treated cells revealed marked alterations of surface membranes. Microtubules and microfilaments appeared normal in "resting" polymorphonuclear leukocytes, but the increase in microtubules normally observed in stimulated cells was not seen after tetracaine treatment. These results suggest that tetracaine interferes with those interactions between immune reactants and the polymorphonuclear leukocyte cell surface which provoke exocytosis and increased oxidative metabolism.
Reproducibility of skin prick testing with allergen extracts from different manufacturers
Authors: I. Eichler, M. Götz, R. Jarisch, H. G. Eichler, R. Moss
Journal: Allergy (1988)

Allergen extracts for skin prick testing (SPT) are available from several manufacturers. Although these solutions are specified according to well-defined internal company standards, there is no generally accepted overall standardization. To assess the comparability of skin prick test solutions of various manufacturers, we compared extracts of nine different allergens from four companies by SPT in 29 children sensitive to one or more of the allergens, in a double blind fashion. RAST (Pharmacia) and EAST (Kallestad) were determined in simultaneous blood samples. Allergen extracts were also examined by rocket immunoelectrophoresis for their content of major allergens. Skin reactions, assessed by mean diameter of wheals, to identical allergen extracts varied significantly between the four vendors (P less than 0.05-0.001). Correlation between RAST and EAST was good for all allergens except birch pollen and mugwort. Content of the major allergen in corresponding extracts varied significantly between the different companies (less than 1%-2000%). These data underline the need for international reference extracts as intracompany standardization of test solutions alone is not enough to yield general reproducibility of skin prick test results.
The making of the Lancet Series on health in the Arab world
Authors: Huda Zurayk, Rita Giacaman, Samer Jabbour, Abdullatif Husseini, Jocelyn DeJong, Dennis Hogan, Marwan Khawaja, Carla Makhlouf Obermeyer, Iman Nuwayhid, Hoda Rashad, Belgin Tekce
Journal: The Lancet (2014)
Toward a Science of Tumor Forecasting for Clinical Oncology
Authors: Thomas E. Yankeelov, Vito Quaranta, Katherine J. Evans, Erin C. Rericha
Journal: Cancer Research (2015)

We propose that the quantitative cancer biology community makes a concerted effort to apply lessons from weather forecasting to develop an analogous methodology for predicting and evaluating tumor growth and treatment response. Currently, the time course of tumor response is not predicted; instead, response is only assessed post hoc by physical examination or imaging methods. This fundamental practice within clinical oncology limits optimization of a treatment regimen for an individual patient, as well as to determine in real time whether the choice was in fact appropriate. This is especially frustrating at a time when a panoply of molecularly targeted therapies is available, and precision genetic or proteomic analyses of tumors are an established reality. By learning from the methods of weather and climate modeling, we submit that the forecasting power of biophysical and biomathematical modeling can be harnessed to hasten the arrival of a field of predictive oncology. With a successful methodology toward tumor forecasting, it should be possible to integrate large tumor-specific datasets of varied types and effectively defeat one cancer patient at a time.
Hepatitis C Virus Infection and Risk of Hepatocellular Carcinoma Among Japanese: Possible Role of Type 1b (II) Infection
Authors: Keitaro Tanaka, Hideyuki Ikematsu, Tomio Hirohata, Seizaburo Kashiwagi
Journal: JNCI Journal of the National Cancer Institute (1996)

Although hepatitis C virus (HCV) infection is recognized as an important risk factor for hepatocellular carcinoma (HCC), the strength of this association has been inconsistent. In addition, the role of specific HCV genotypes in HCC progression has not yet been determined. We conducted a case—control study to estimate the relative risk (RR) of HCC in relation to HCV infection among residents of the Fukuoka Prefecture, where HCC risk is among the highest in Japan, and to examine whether the risk differs according to HCV genotypes and/or HCV RNA titers. Stored serum samples obtained from 91 patients with HCC and 410 healthy control subjects, who had been frequency matched to the patients with regard to sex and age, were tested for antibodies to HCV by use of second-generation immunoradiometric and immunoblot assays. The presence of serum HCV RNA and of specific HCV genotypes was determined by use of polymerase chain reaction-based assays, and HCV RNA titers were measured by use of a branched DNA assay. Antibodies to HCV were detected in 71 patients (78.0%) and in 30 control subjects (7.3%), of whom 57 patients and 25 control subjects had serum HCV RNA. One patient was positive for HCV RNA but not for antibodies to HCV. The sex-and age-adjusted RR of HCC among individuals positive for antibodies to HCV was estimated to be 53.7 (95% confidence interval [CI] = 27.1–106.2). Antibodies to HCV were much more prevalent among patients negative for serum hepatitis B surface antigen (HBsAg) (69 of 72, 95.8%) than among HBsAg-positive patients (two of 19, 10.5%); the RR increased to 339.6 (95% CI = 96.5–1195.8) in the separate analysis of HBsAg-negative subjects. The most frequent genotype among HCV RNA-positive subjects was type lb (also called type II) (found in 49 [86.0%] of 57 patients and in 15 [60.0%] of 25 control subjects); individuals with type 1b infection experienced a significantly elevated risk (RR = 3.8; 95% CI = 1.0–13.9) compared with the risk observed for individuals with type 2a (also called type III) infection. No statistically significant association between HCV RNA titers and HCC was evident. HCV infection, particularly type 1b infection, plays an important role in the development of HCC among the study population. We estimated that approximately 78% (95% CI = 69%86%) of the HCCs that occur in this high-risk area are attributable to HCV infection, if we assume that the patients in this study were representative population samples. Further studies are needed to clarify potential risk factors, including specific HCV genotypes, for progression to HCC among HCV carriers.
Cofibrins and Fibrin-Intermediates as Indicators of Thrombin Activity in Vivo
Authors: JOHN R. SHAINOFF, IRVINE H. PAGE, Miss Dolores Andrasi
Journal: Circulation Research (1960)

A cold-precipitable, thrombin-coagulable protein, tentatively designated "cryoprofibrin," was separated from plasma of rabbits treated with E. coli endotoxin. It was shown to contain fibrin-intermediates, consisting of fibrinogen that has lost only a portion of the peptides liberated during the conversion of rabbit fibrinogen to fibrin. These peptides have been called cofibrins. On reaction with thrombin, fibrinogen and cryoprofibrin yielded the same amount of cofibrin B (0.9 moles per 220,000 Gm. of fibrin clot); however, cryoprofibrin yielded 30 per cent less cofibrin A than did fibrinogen. Cryoprofibrin and fibrinogen yielded 0.7 and 1.0 moles of cofibrin A per 220,000 Gm. of fibrin, respectively. The deficit of cofibrin A in preference to cofibrin B provides evidence that, cryoprofibrin consists of fibrinogen that had lost cofibrin A by limited action of thrombin, because cofibrin A is liberated from fibrinogen by thrombin more rapidly than is cofibrin B. Only a small portion of the cryoprofibrin could have been produced by action of thrombin subsequent to exsanguination, because the plasma contained only about one-third of the cofibrin A that had been liberated from fibrin-ogen during its conversion to cryoprofibrin. Accordingly, cryoprofibrin provides a valid measure of thrombin activity in vivo, at least in the endotoxin-treated rabbits. An alternative approach to measurement of thrombin activity involving recovery of cofibrin A from urine proved inapplicable, because no confibrin A was found to be excreted in urine. An average of 0.264 ± 0.038 mg. cryoprofibrin per ml. was obtained from plasma of treated rabbits, as compared with 0.044 ± 0.016 mg. of cold-precipitable fibrinogen per ml. of normal plasma. The demonstration of increased thrombin activity after endotoxin treatment, as evidenced by the cryoprofibrin, implicates thrombin in the mechanism of fibrinoid deposition. The demonstration that cryoprofibrin consists of fibrin-intermediates supports Thomas' hypothesis that fibrinoid consists of fibrin-intermediates.