tbuckley/cabot-search huggingface dataset:
Evidence of a natural killer (NK) cell repertoire for (allo) antigen recognition: definition of five distinct NK-determined allospecificities in humans.
Authors: E Ciccone, D Pende, O Viale, C Di Donato, G Tripodi, A M Orengo, J Guardiola, A Moretta, L Moretta
Journal: The Journal of Experimental Medicine (1992)

Previous studies indicated that CD3-CD16+ natural killer (NK) cells are capable of specific alloantigen recognition. Thus, alloreactive NK clones lysed normal allogeneic target cells (phytohemagglutinin [PHA] blasts) bearing the stimulating alloantigen but did not lyse autologous cells or the majority of unrelated allogeneic cells. In this study we investigated whether NK cells isolated from single individuals could exhibit different allospecificities. To this end, we derived large numbers of CD3-CD16+ clones (in the presence of PHA) from fresh CD3- peripheral blood lymphocytes. Cloning efficiencies ranged between 5 and 10%. The resulting CD3-CD16+ clones were tested for their reactivity against a panel of allogeneic PHA blasts (derived from six donors). In a given individual (A), four distinct groups of clones could be identified according to their pattern of reactivity (over 400 clones have been analyzed). Clones that could be assigned to one or another group of specificity represented 36% of all clones derived from this donor. The remaining clones did not display cytolytic activity against any of the allogeneic target cells used in the panel. None of the clones lysed autologous (A) PHA blasts, yet, these cells were lysed by the representative clones G10 and H12 specific for donor A. Clones displaying a cytolytic pattern of reactivity identical to that defined for donor A were present in other individuals studied, however not all groups of allospecific clones were necessarily represented in different individuals. Allospecific clones belonging to the various groups were homogeneous in the expression of EB6/GL183-triggering surface molecules, and could thus be assigned to one or another of the previously defined subsets of NK cells. Genetic analysis of the new NK-defined alloantigens was performed in representative families. The corresponding characters were found to segregate independently and, at least for three of them, an autosomic recessive type of inheritance could be demonstrated. Moreover, the comparative analysis of the segregation of the major histocompatibility complex haplotypes and the recessive or dominant alleles of the genes governing the five specificities analyzed indicated that there is no independent sampling between the two genetic traits, thus suggesting that the genes regulating the NK-defined specificities are carried by chromosome 6. Finally, some donors expressed more than one specificity, thus providing evidence for an NK-defined complex haplotype.
Prevalence of childhood asthma and allergic diseases in Ankara, Turkey
Authors: A. F. Kalyoncu, Z. T. Selçuk, Y. Karakoca, A. S. Emri, L. Çöplü, A. A. Şahin, Y. I. Bariş
Journal: Allergy (1994)

Kalyoncu AF, Selçuk ZT, Karakoca Y, Emri AS, Çöplü L, Şahin AA, Bariş YI. Prevalence of childhood asthma and allergic diseases in Ankara, Turkey. The first epidemiologic survey of the prevalence of childhood asthma and other allergic disease in Ankara, Turkey, was done in May 1992. A questionnaire on factors influencing the atopic status and allergic symptoms was distributed to parents of 1226 children aged 6‐12 years. In this questionnaire, parents were asked to give information about physician‐diagnosed asthma and atopic dermatitis (AD), and self‐reported wheezing and rhinoconjunctivitis (perennial or seasonal). The overall response rate was 85 % and included 502 boys (48.5%) and 534 girls (51.5%). The lifetime prevalences of asthma, wheezing, rhinoconjunctivitis, and AD were 17.4%, 23.3%, 28%, and 6.1%, respectively, and the reported prevalences for the last 12 months were 8.3%, 11.9%, 15.4%, and 4%, respectively. Asthma and other allergic disease had been recognized in 23.2% of the children during the last year; in half of these, more than one disease was present. Eight percent of the families kept pet animals; 95.4% of children had been breast‐fed, of whom 61% for more than 6 months; and at least one person smoked at home in the case of 73.9% of children. Some health insurance was available to 72.8% of the families. Cumulative prevalences of wheezing, rhinoconjunctivitis, and AD were significantly associated with the presence of pets, passive smoking at home, and absence of health insurance. The prevalence of asthma was not affected by any of these factors except atopic family history. In conclusion, asthma and other allergic diseases constitute a major health problem for schoolchildren in Ankara.
Epidemiological and virological analysis of couples infected with hepatitis C virus
Authors: H Zylberberg, V Thiers, D Lagorce, G Squadrito, F Leone, P Berthelot, C Brechot, S Pol
Journal: Gut (1999)

<h3>BACKGROUND</h3> If transmission of hepatitis C virus (HCV) infection through parenteral exposure is well documented, sexual transmission of HCV is still debated. <h3>AIMS</h3> To perform extensive epidemiological and virological analysis in 24 couples in which each spouse was anti-HCV positive in order to delineate more precisely potential sexual transmission of HCV. <h3>PATIENTS</h3> Twenty four couples in which each partner was anti-HCV positive. These 48 spouses were recruited in a liver unit by regular screening of spouses of index patients. <h3>METHODS</h3> All 48 spouses completed an epidemiological questionnaire on risk factors for HCV. Qualitative detection of serum HCV RNA and determination of HCV type by genotyping and serotyping were performed. Sequence analysis of HCV strains by phylogenetic analysis was carried out in seven couples with concordant genotypes. <h3>RESULTS</h3> The mean (SD) partnership duration was 12 (10) years. Serum HCV RNA was detected in both partners in 18 of the couples (75%) and in only one partner in six of the couples (25%). HCV typing showed concordant genotypes in 12 couples (50%), discordant genotypes in seven (29%), and in the other five couples (21%) only one spouse could be genotyped. Of the 48 spouses, 33 had a major risk factor for HCV transmission such as transfusion (n = 6) and intravenous drug use (n = 27). Eleven of the 12 couples infected with the same HCV genotype had at least one parenteral risk factor for viral transmission in both spouses. Whatever the genotype concordance, in most couples (75%), both spouses showed parenteral risk factors for viral transmission. Sequence analysis of HCV strains was possible in seven of 12 couples with identical genotype and showed different and identical isolates in four and three couples respectively. <h3>CONCLUSION</h3> The study emphasises the risk of overestimating the importance of a very low sexual HCV transmission risk as against other, mainly parenteral, risk factors.
Points from Letters: Test Tube Babies
Authors: N. L. M. Reader
Journal: BMJ (1970)

refers I did not comment directly on the case for or against a large increase in number, but was concerned with the evi- dence indicating that the Royal Commission had failed to understand the mathematical basis on which they proposed an exponential expansion, and had thus reached a wholly unjustifiable conclusion about the number of doctors necessary.I also drew attention to the implications of an error of this magnitude, which could require perhaps the provision of 10,000 unnecessary doctors in 10 years, a number equivalent to the output of five new medical schools.As this appears a serious matter, one would expect the mathematical errors in this section of the report to have been ac- knowledged and corrected before now, since it must surely be necessary to prepare a new estimate based on less indefensible grounds.If, however, my conclusions are unjustified, it should be an easy matter to refute them.-Iam, etc.,
Velocity fields and turbulent stresses downstream of biological and mechanical aortic valve prostheses implanted in pigs
Authors: J M. HASENKAM, E. M. PEDERSEN, J. H. OSTERGAARD, H. NYGAARD, P. K. PAULSEN, G. JOHANNSEN, B. A. SCHURIZEK
Journal: Cardiovascular Research (1988)

Since detailed knowledge about velocity fields downstream of heart valve prostheses obtained from in vitro studies has not been followed up by similar detailed studies in vivo a pig model for acute velocity field studies downstream of aortic valve prostheses was established. Two mechanical and two bioprosthetic valves were studied and a dynamic three dimensional visualisation of velocity fields one diameter downstream performed under different haemodynamic conditions in a total of 22 pigs. The Ionescu-Shiley pericardial valve had velocity fields very similar to the normal native porcine aortic valve. The Edwards-Carpentier porcine valve caused a jet type flow, and the valve design of the St Jude Medical and Björk-Shiley Monostrut valves was reflected in the velocity profile. Normalised (mean(SEM] systolic Reynolds normal stresses in the total cross sectional area were: native porcine 15(1.5) Nm-2; St Jude Medical 24(3.4) Nm-2; Björk-Shiley Monostrut 25(1.6) Nm-2; Edwards-Carpentier Supra-annular 51(6.6) Nm-2; Ionescu-Shiley Pericardial 19(2.0) Nm-2. Reynolds normal stresses were higher in areas of rapidly changing or constantly high velocity gradients.
Acute lower leg compartment syndrome.
Authors: R A Power, P Greengross
Journal: British Journal of Sports Medicine (1991)

Acute compartment syndromes in the lower leg are well recognized following major trauma. However, although rare, they may occur following seemingly minor sporting injury. A case of acute compartment syndrome, following a football game and affecting the peroneal or lateral compartment, is described, in which prompt diagnosis and treatment led to a satisfactory outcome. The diagnosis and surgical management of acute compartment syndromes are discussed. Early recognition and treatment are important in the prevention of long-term disability.
Fishing penetration injuries
Authors: I Dudkiewicz, M Salai, A Blankstein, A Chechik
Journal: British Journal of Sports Medicine (2000)

Background —Fishing involves millions of people throughout the world and is considered a pleasant and harmless sport. However, many kinds of injury can occur. Penetrating injuries to the extremities by fishing equipment such as hooks and harpoons, and even by scales, or infection from penetration of scales etc are relatively common although hardly ever reported in the literature. Methods —Illustrative cases of penetrating fishing injuries are presented and discussed, with suggestions for the recommended management of these types of injury. Results —Most of these objects are designed to catch and hold resisting fish, so are usually sharp and narrow in the front and wider in the rear with or without spurs. Because of their very irregular shape, simple extraction by pulling is not recommended, because further damage may occur. Conclusions —The use of the appropriate imaging modalities, a full knowledge of the contours of the object, and careful preplanning of the method of treatment are very important.
Bone Morphogenic Protein-4 Impairs Endothelial Function Through Oxidative Stress–Dependent Cyclooxygenase-2 Upregulation
Authors: Wing Tak Wong, Xiao Yu Tian, Yangchao Chen, Fung Ping Leung, Limei Liu, Hung Kay Lee, Chi Fai Ng, Aimin Xu, Xiaoqiang Yao, Paul M. Vanhoutte, George L. Tipoe, Yu Huang
Journal: Circulation Research (2010)

Rationale: Bone morphogenic protein (BMP)4 can stimulate superoxide production and exert proinflammatory effects on the endothelium. The underlying mechanisms of how BMP4 mediates endothelial dysfunction and hypertension remain elusive. Objective: To elucidate the cellular pathways by which BMP4-induced endothelial dysfunction is mediated through oxidative stress–dependent upregulation of cyclooxygenase (COX)-2. Methods and Results: Impaired endothelium-dependent relaxations, exaggerated endothelium-dependent contractions, and reactive oxygen species (ROS) production were observed in BMP4-treated mouse aortae, which were prevented by the BMP4 antagonist noggin. Pharmacological inhibition with thromboxane prostanoid receptor antagonist or COX-2 but not COX-1 inhibitor prevented BMP4-induced endothelial dysfunction, which was further confirmed with the use of COX-1 −/− or COX-2 −/− mice. Noggin and knockdown of BMP receptor 1A abolished endothelium-dependent contractions and COX-2 upregulation in BMP4-treated aortae. Apocynin and tempol treatment were effective in restoring endothelium-dependent relaxations, preventing endothelium-dependent contractions and eliminating ROS overproduction and COX-2 overexpression in BMP4-treated aortae. BMP4 increased p38 mitogen-activated protein kinase (MAPK) activity through a ROS-sensitive mechanism and p38 MAPK inhibitor prevented BMP4-induced endothelial dysfunction. COX-2 inhibition blocked the effect of BMP4 without affecting BMP4-induced ROS overproduction and COX-2 upregulation. Importantly, renal arteries from hypertensive rats and humans showed higher levels of COX-2 and BMP4 accompanied by endothelial dysfunction. Conclusions: We show for the first time that ROS serve as a pathological link between BMP4 stimulation and the downstream COX-2 upregulation in endothelial cells, leading to endothelial dysfunction through ROS-dependent p38 MAPK activation. This BMP4/ROS/COX-2 cascade is important in the maintenance of endothelial dysfunction in hypertension.
Suicide, deprivation, and unemployment: record linkage study
Authors: G. Lewis, A. Sloggett
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objectives</b> : To investigate the association between suicide and socioeconomic status, unemployment, and chronic illness. <b>Design</b> : Longitudinal study. <b>Setting</b> : England and Wales. <b>Subjects</b> : Individuals from the Office for National Statistics longitudinal study for whom 1981 census data were available. The longitudinal study is a representative 1% sample of the population of England and Wales in which census variables are linked to mortality data. <b>Main outcome measures</b> : Suicide and undetermined deaths occurring between 1983 and 1992. Odds ratios estimated with logistic regression adjusted for attrition of cohort members. <b>Results</b> : There was a strong independent association between suicide and individuals who were unemployed (odds ratio 2.6; 95% confidence interval 2.0 to 3.4) and permanently sick (2.5; 1.6 to 4.0). Those without access to a car had an increased risk (1.3; 1.0 to 1.5), but other measures of socioeconomic status were not associated with suicide. <b>Conclusions</b> : The association between suicide and unemployment is more important than the association with other socioeconomic measures. Although some potentially important confounders were not adjusted for, the findings support the idea that unemployment or lack of job security increases the risk of suicide and that social and economic policies that reduce unemployment will also reduce the rate of suicide.
What role for theophylline?
Authors: J W Jenne
Journal: Thorax (1994)

<b>Objective: </b>To evaluate the predictive value of the Quix test in identifying a vestibular abnormality in the non-vertiginous dizzy patient. <b>Background: </b>The evaluation of the dizzy patient poses a major challenge for physicians. Previously, we reported the Quix test’s usefulness in determining the involved side in BPPV; however, properly performed, the Quix test may also uncover a vestibular component in patients with multiple comorbidities. <b>Methods: </b>Two-hundred patients were evaluated at a Balance Disorders Clinic with chief complaints of dizziness, vertigo, or imbalance. We administered the Quix test (patient’s eyes closed, feet opposed, arms extended toward target, 2.5 cm deviation considered positive) prior to standard testing videonystagmography (VNG) and dynamic platform posturography (DPP). Eighty-four patients were classified by Drachmann’s criteria as type II (syncope), III (upright instability), or IV (anxiolytic). The study focused on patients with dizziness; the remaining 116 patients categorized as Drachmann I (vertigo) were excluded. Patients were determined to have a vestibular abnormality if VNG revealed canal paresis, visually suppressed nystagmus, or failure to maintain balance in vestibular derived conditions on DPP. <b>Results: </b>A logistic regression was performed to ascertain the effect of a positive Quix test in predicting the likelihood of vestibular involvement in the patient’s dizziness. The Quix test was a statistically significant predictor variable of vestibular abnormality, (p &lt; .0005). The model explained 29[percnt] (Nagelkerke R2) of the variance and correctly classified 73.8[percnt] of cases. The sensitivity was 70.8[percnt] and specificity was 77.8[percnt]. <b>Conclusions: </b>A positive Quix test helps identify a vestibular abnormality in patients with generic dizziness. A negative test raises the likelihood of an alternative diagnosis. As a complementary tool, it provides valuable insight in patient evaluation. Absent of proven clinical examination techniques that identify vestibular abnormalities, the Quix test proves to be a critical tool in the evaluation of the dizzy patient. <b>Disclosure:</b> Dr. Reese has nothing to disclose. Dr. Zuchowski has nothing to disclose. Dr. Barr has nothing to disclose. Dr. Evan has nothing to disclose. Dr. Maitland has nothing to disclose.
Chronic viral hepatitis induced by hepatitis C but not hepatitis B virus infection correlates with increased liver angiogenesis
Authors: R. Mazzanti, L. Messerini, L. Monsacchi, G. Buzzelli, A. L. Zignego, M. Foschi, M. Monti, G. Laffi, L. Morbidelli, O. Fantappié, Bartoloni Saint F. Omer, M. Ziche
Journal: Hepatology (1997)

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections lead to cirrhosis and increase the risk for the development of hepatocellular carcinoma (HCC). Angiogenesis is an essential step in oncogenesis and contributes to tumor progression in adult organs; however, to what extent angiogenesis occurs in the liver during chronic viral hepatitis has not been studied. Ninety–nine matched patients affected by chronic hepatitis due to either HBV or HCV were studied together with 13 controls (5 patients were affected by familial hyperbilirubinemia with normal liver histology; 6 patients with stage II primary biliary cirrhosis; and 2 patients with pseudo inflammatory tumor). Microvessel density was assessed in liver biopsies by immunostaining using two different antibodies against endothelial cell antigens, QB–END/10 and Factor VIII. In addition, the liver homogenates and sera of HCV– or HBV–positive patients and controls were tested for their capacity to stimulate the migration and proliferation of freshly isolated human endothelial cells in vitro. Evidence of angiogenesis was significantly more frequent in HCV–positive patients compared with HBV–infected subjects or controls (74% vs. 39% vs. 8%) (χ2 = 20.78; P &lt; .0001) (HCV+ vs. HBV+ vs. controls). The degree of microvessel density was also higher in HCV– than in HBV–positive patients or controls (χ2 = 12.28; P &lt; .005). In addition, HCV–positive sera and liver homogenates stimulated a higher migration and proliferation of human endothelial cells in vitro compared with HBV–positive or control sera and liver homogenates. These observations indicate that angiogenesis is particularly linked to HCV infection, suggesting a possible contribution to HCV–related liver oncogenesis.
Correction of Clinical Manifestations of Canine Mucopolysaccharidosis I with Neonatal Retroviral Vector Gene Therapy
Authors: Anne M Traas, Ping Wang, Xiucui Ma, Mindy Tittiger, Laura Schaller, Patricia O'donnell, Meg M Sleeper, Charles Vite, Ramin Herati, Gustavo D Aguirre, Mark Haskins, Katherine P Ponder
Journal: Molecular Therapy (2007)

Mucopolysaccharidosis I (MPS I) (Hurler syndrome) is due to deficient α-l-iduronidase (IDUA) activity and is the most common of the MPS disorders. Neonatal MPS I dogs were injected intravenously (IV) with a gamma retroviral vector containing a complete long-terminal repeat (LTR) and an internal human α1-antitrypsin (hAAT) promoter upstream of the canine IDUA complementary DNA (cDNA). This resulted in stable serum IDUA activity of 366 ± 344 units (U)/ml (28-fold normal) for up to 1.8 years, which likely derived primarily from secretion of IDUA by transduced liver cells. Retroviral vector (RV)-treated dogs had >18% of normal IDUA activity in organs and had decreased severity and/or incidence of hernias, chest deformities, joint disease, facial dysmorphia, corneal clouding, valvular heart disease, and aortic dilatation as compared with untreated MPS I dogs. The marked reduction that was observed in lysosomal storage in the brain of RV-treated dogs may have been due in part to expression from the LTR of the vector in cells in the brain. This possibility will be explored in future studies, because the potential for insertional mutagenesis has raised concerns about using vectors with an intact LTR. If proven safe, this gene therapy technique may be utilized in treating children with Hurler syndrome. Mucopolysaccharidosis I (MPS I) (Hurler syndrome) is due to deficient α-l-iduronidase (IDUA) activity and is the most common of the MPS disorders. Neonatal MPS I dogs were injected intravenously (IV) with a gamma retroviral vector containing a complete long-terminal repeat (LTR) and an internal human α1-antitrypsin (hAAT) promoter upstream of the canine IDUA complementary DNA (cDNA). This resulted in stable serum IDUA activity of 366 ± 344 units (U)/ml (28-fold normal) for up to 1.8 years, which likely derived primarily from secretion of IDUA by transduced liver cells. Retroviral vector (RV)-treated dogs had >18% of normal IDUA activity in organs and had decreased severity and/or incidence of hernias, chest deformities, joint disease, facial dysmorphia, corneal clouding, valvular heart disease, and aortic dilatation as compared with untreated MPS I dogs. The marked reduction that was observed in lysosomal storage in the brain of RV-treated dogs may have been due in part to expression from the LTR of the vector in cells in the brain. This possibility will be explored in future studies, because the potential for insertional mutagenesis has raised concerns about using vectors with an intact LTR. If proven safe, this gene therapy technique may be utilized in treating children with Hurler syndrome.
Nonhuman primate models of asthma
Authors: Robert L. Coffman, Edith M. Hessel
Journal: The Journal of Experimental Medicine (2005)

Asthma is a complex human disease that does not have an accurate counterpart in any common model organism. Most of our understanding of the immune mechanisms underlying asthma comes from studies in man and mouse. However, there are fundamental differences between the spontaneous disease in man and the experimentally induced counterparts in mice. We advocate more extensive use of nonhuman primate asthma models to reconcile these differences between man and mouse.