tbuckley/cabot-search huggingface dataset:
Sequestration of Adenoviral Vector by Kupffer Cells Leads to a Nonlinear Dose Response of Transduction in Liver
Authors: Nianjun Tao, Guang-Ping Gao, Michael Parr, Julie Johnston, Timothy Baradet, James M. Wilson, James Barsoum, Stephen E. Fawell
Journal: Molecular Therapy (2001)

Systemic administration of a recombinant adenovirus encoding the human interferon-β gene (H5.110CMVhIFN-β) results in transduction of hepatocytes and detectable circulating levels of IFN-β protein. In preclinical studies in mice, we noticed a distinctly nonlinear dose response, with low levels of virus (1–3 × 1010 viral particles) yielding barely detectable levels of IFN-β but with a higher viral dose (1 × 1011 particles) resulting in disproportionately high IFN-β levels. Further studies showed that transgene expression levels from low viral doses could be dramatically enhanced by coadministering an unrelated recombinant adenovirus (H5.110CMVlacZ), suggesting that there was a viral dose threshold effect for efficient viral transduction and/or IFN-β expression. This enhancement of reporter expression by a nonreporter adenovirus, effective upon coadministration, was further enhanced by preadministration of H5.110CMVlacZ (up to 8 h), but was ineffective if the helper virus was administered as little as 5 min after the H5.110CMVhIFN-β reporter virus. Our data suggest that the reticuloendothelial system plays a role in this threshold effect, such that low doses of virus are efficiently taken up by the RES/Kupffer cells without leading to appreciable transgene expression, whereas high doses saturate these cells and are able to productively transduce hepatocytes. A better understanding of this phenomenon could have an impact on gene therapy clinical trial safety and efficacy.
Collections of Subdural Fluid Complicating Meningitis Due to<i>Haemophilus influenzae</i>(Type B)
Authors: R. James McKay, Russell A. Morissette, Franc D. Ingraham, Donald D. Matson
Journal: New England Journal of Medicine (1950)

THE incidence of recovery from acute bacterial meningitis has risen sharply since the introduction of modern antibiotic therapy. With this rise various untoward sequelae have become evident in patients who formerly would not have survived. It is the purpose of this preliminary report to describe the occurrence of collections of xanthochromic subdural fluid of high protein content, most of which are encapsulated, in infants and small children surviving the acute phase of meningitis due to Haemophilus influenzae (Type B). This complication was first noted in a review of the records of patients treated for this disease during the last three . . .
NICE advises against caesarean section on demand
Authors: Zosia Kmietowicz
Journal: BMJ (2004)

<h3>Objective</h3> To identify associations between the weight groups underweight (UW), overweight (OW) and obesity (OB) at 5 years of age and exposures related to pregnancy, anthropometric measures at birth, sociodemographic factors, and family health, anthropometric measures and habits. <h3>Design</h3> Regional cohort study. <h3>Setting</h3> Oppland County, Norway. <h3>Methods</h3> Pregnancy data were obtained from a prospective perinatal register for children born in the county, and weight and height were measured by midwives at birth and by public health nurses at 5 years. Other information was obtained from questionnaires completed by parents. <h3>Participants</h3> Of 1895 eligible children, current weight and height were obtained for all, weight and length at birth and information from parents for 1119 (59%) and pregnancy register data for 749 (40%) of the children. The significance of potential explanatory variables from descriptive statistics was tested in multinomial logistic regression analysis. <h3>Results</h3> The prevalence of UW, OW and OB among participants was 7.8%, 10.6% and 3.5%, respectively. UW was associated with anthropometric measures at birth and those of parents, but not with sociodemographic or behavioural characteristics. OW and OB were associated with anthropometric measures of parents and siblings and with a variety of unfavourable social characteristics, lack of prolonged breast feeding, sedentary behaviour and dental caries, but not with current dietary habits. After adjustments, OW and OB were marginally related to birth parameters and diet and unrelated to physical activity, but significantly related to parental body mass index, low parental education and maternal smoking. <h3>Conclusion</h3> The strong associations between sociodemographic and behavioural factors and OW and OB, but not with UW, may suggest that environmental factors are major contributing causes of OW and particularly OB at 5 years. These results may be helpful in targeting preventive measures against OW and OB.
35‐year‐old patient with chronic myelogenous leukemia developing systemic lupus erythematosus after α‐interferon therapy
Authors: Nilesh D. Mehta, Arthur L. Hooberman, Everett E. Vokes, Scott Neeley, Scott Cotler
Journal: American Journal of Hematology (1992)

The maculopapular rash recurred in December 1990, associated with fever, severe arthralgias, and headaches.Alpha-interferon was discontinued out of concern that it may be exacerbating the patient's condition.She was admitted to the University of Chicago in January 1991 for evaluation of worsening rash and fever.On physical examination, her temperature was 38.2"C.A blanching maculopapular rash was present over the malar areas of her face, trunk, and limbs.Upper extremity lesions were concentrated over the elbows.Musculoskeletal examination revealed tenderness and swelling of metacatpophalangeal joints bilaterally.The rest of her physical examination was normal except for splenomegaly, which was unchanged.Laboratory examination revealed a hematocrit of 35.4%; white count was 7,900 with 93% polys, 4% bands, and 1 % lymphocytes.Liver function abnormalities included an alkaline phosphatase of 246 (normal: 33-13 1 IU) and a SGOT of 40 IU (normal <35).An anti-nuclear antibody was elevated at 200 (nl 0-50) with a speckled pattern, double stranded DNA titer was
Ectopic calcification around joints of paralysed limbs in hemiplegia, diffuse brain damage, and other neurological diseases.
Authors: A J Rosin
Journal: Annals of the Rheumatic Diseases (1975)

Mechanical deformity associated, with neurological disease is commonly encountered in the form of contractures, or pre-existing arthritis. Less common is the occurrence of ectopic calcification around the joints of a paralysed limb. Two forms of this are presented in a series of twenty patients. Para-articular calcification with the appearance of myositis ossificans around large joints of the affected limbs occurred most often. The interior of the joints was not affected, nor was there evidence of bony injury. In some cases, however, the excessive outgrowth of bone around the joint eventually resulted in a functional ankylosis by a uniting bar of bone outside the joint. The second form of calcification was periosteal, which unlike the first type was resorbed and left an area of cortical bony thickening.
Amelioration of allergic airway inflammation in mice by regulatory <scp>IL</scp>‐35 through dampening inflammatory dendritic cells
Authors: J. Dong, C. K. Wong, Z. Cai, D. Jiao, M. Chu, C. W. K. Lam
Journal: Allergy (2015)

Abstract Background IL ‐35, a new member of the IL ‐12 family, is an inhibitory cytokine produced by regulatory T and B lymphocytes that play a suppressive role in the inflammatory diseases. This study focuses on the cellular mechanism regulating the anti‐inflammatory activity of IL ‐35 in asthmatic mice. Methods Ovalbumin‐induced asthmatic and humanized asthmatic mice were adopted to evaluate the in vivo anti‐inflammatory activities of IL ‐35. For monitoring the airway, Penh value (% baseline) was measured using a whole‐body plethysmograph. Results In this study using ovalbumin‐induced asthmatic mice, we observed that intraperitoneal injection of IL ‐35 during the allergen sensitization stage was more efficient than administration in the challenge stage for the amelioration of airway hyper‐responsiveness. This was reflected by the significantly reduced concentration of asthma‐related T h2 cytokines IL ‐5 and IL ‐13, as well as eosinophil counts in bronchoalveolar lavage fluid (all P &lt; 0.05). IL ‐35 also significantly attenuated the accumulation of migratory CD 11b+ CD 103 − dendritic cells ( DC ) in the mediastinal lymph node ( mLN ) and lung of mice (all P &lt; 0.05). IL ‐35 markedly inhibited the ovalbumin‐induced conversion of recruited monocytes into inflammatory DC , which were then substantially reduced in m LN to cause less T ‐cell proliferation (all P &lt; 0.05). Further study using the humanized asthmatic murine model also indicated human IL ‐35 exhibited a regulatory impact on allergic asthma. Conclusion Our findings suggest that IL ‐35 can act as a crucial regulatory cytokine to inhibit the development of allergic airway inflammation via suppressing the formation of inflammatory DC at the inflammatory site and their accumulation in the draining lymph nodes.
e/ANTI-e, RHEUMATOID FACTOR, AND LIVER DISEASE
Authors: Seiichi Furuta, Atsuo Nagata, Kendo Kiyosawa, Shinkichi Yamamura, Ken Sodeyama, Masayuki Oda, Makoto Mayumi, Kirsten Anderson-Visoná, Alvaro Gutiérrez-Diermissen, VíctorM. Villarejos
Journal: The Lancet (1977)
Of indigenous people and their health
Authors: I. Loefler
Journal: Journal of the Royal Society of Medicine (2007)

‘Indigenous’ is the politically correct version of the word ‘native’, used by the white man in reference to the peoples he ‘discovered’ upon exploring and subsequently colonizing the globe. The word native had, until the middle of the 20th century, the connotation of primitive and uncivilized people, recognizable by virtue of skin pigmentation. The replacement word, indigenous, came into use during the independence movement and has acquired several new connotations. The indigenous have suffered and continue to suffer injustice, they are disadvantaged, ‘challenged’, and must be helped to attain the ‘civilized’ status of Western man, as measured by means constructed by Western man—such as the human development index, the Disability Adjusted Life Years (DALY) rates, and ultimately, life expectancy at birth. Indigenous people should attain equity in all the ‘civilized’ achievements.
Resistance of the Suckling Guinea Pig to Lithocholic Acid-Induced Cholestasis
Authors: Malka Lewittes, Beatrix Tuchweber, Andree Weber, Claude C. Roy, Ibrahim M. Yousef
Journal: Hepatology (1984)

Although immaturity of the liver and synthesis of monohydroxy bile acids have been implicated as pathogenic factors in neonatal cholestasis, there is no direct evidence to show that these bile acids induce cholestasis in the newborn. In the present investigation, we compared the effects of lithocholic acid (LCA) injection on bile flow in suckling (2-week-old) and adult (12-week-old) guinea pigs. Bile flow was not modified by LCA in 2-week-old animals, but it was reduced by 50 to 80% in the adults, the decrease being dose-dependent. In the newborn, the injected LCA was mainly secreted in bile (&gt;90%), while in the adults it was distributed between the liver and bile. The percentage of biliary bile acids (as determined by gas-liquid chromatography) in the two groups was similar before and after LCA injection. Morphologic lesions characteristic of LCA-induced cholestasis were observed only in the adult guinea pigs. This study demonstrates that the newborn guinea pig is less susceptible to cholestasis induced by 90 to 180 /imoles per kg body weight of lithocholate and that, in the neonatal liver, there is no defect in the transport of this bile acid from blood to bile.
A current genotoxicity database for heterocyclic thermic food mutagens. I. Genetically relevant endpoints.
Authors: F T Hatch
Journal: Environmental Health Perspectives (1986)

Cooking, heat processing, or pyrolysis of protein-rich foods induce the formation of a series of structurally related heterocyclic aromatic bases that have been found to be mutagens. The primary genetic assay utilized to detect and isolate these mutagens has been the his reversion assay in Salmonella typhimurium. The classification and nomenclature of these chemicals is revised to reflect recent advances. The findings of short-term tests for genetic injury that have been applied to these agents are presented in a systematic way. Cell-free, bacterial, mammalian cell culture, and in vivo systems are included. Major results, the mutagens tested, and key references are presented in tabular form, with text commentary. Integrated conclusions on the state of current knowledge of the genetic toxicity of thermic food mutagens are presented. Areas in need of further research are defined. Finally, an outline is presented of a suggested path leading to the determination whether normal methods of food preparation and processing constitute a human health hazard.
Autoimmunity to collagen in adjuvant arthritis of rats.
Authors: D E Trentham, W J McCune, P Susman, J R David
Journal: Journal of Clinical Investigation (1980)

Arthritis can be induced in rats by intradermal injection of oil containing bacterial derivatives (adjuvant-induced arthritis) or cartilage collagen (type II collagen-induced arthritis). It was of interest, therefore, to determine whether collagen functions as an autoantigen in rats with adjuvant arthritis. Blood mononuclear cells from the majority of rats with adjuvant arthritis exhibited enhanced thymidine incorporation to homologous types I and II collagens, as well as to purified protein derivative of tuberculin. In contrast, cells from rats remaining nonarthritic after injection of adjuvant did not respond to collagen, although they did react to tuberculin. Similar results were obtained with a radiometric ear assay used to quantify intradermal delayed-type hypersensitivity in vivo. Using passive hemagglutination, autoantibodies to these collagens and their denatured alpha-chains were frequently detected in the sera of rats late in the course of adjuvant arthritis. Rats with inflammation of a hindlimb induced by turpentine did not acquire sensitivity to collagen. These data indicate that autoimmunity to collagen is a common feature of adjuvant- and collagen-induced arthritis, both of which are considered to be mediated by immunologic mechanisms.
Dendritic cells cross-presenting tumor-derived antigens are eliminated by invariant natural killer T (iNKT) cells, impairing development of anti-tumor immunity to a mouse carcinoma
Authors: Karsten A Pilones, Joseph Aryankalayil, Silvia Formenti, Sandra Demaria
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts iNKT cells are CD1d-restricted T cells that are rapidly activated in response to antigen and play a key role in promoting adaptive anti-tumor immunity. Surprisingly, we found that mice bearing 4T1 breast cancer CD8+ T cells inhibited spontaneous metastases in the absence of iNKT
Herpes Simplex Virus Infection as a Cause of Benign Recurrent Lymphocytic Meningitis
Authors: Davol G. Tedder
Journal: Annals of Internal Medicine (1994)

Objective: To identify the role of herpes simplex virus (HSV) in causing benign recurrent lymphocytic meningitis. Design: Prospective cohort study. Setting: Tertiary referral center. Patients: 20 consecutive patients with a provisional diagnosis of benign recurrent lymphocytic meningitis had cerebrospinal fluid specimens submitted between 1990 and 1993 to the diagnostic virology laboratory. Thirteen patients met our criteria for benign recurrent lymphocytic meningitis. Measurements: Herpes simplex virus DNA was detected in cerebrospinal fluid specimens using the polymerase chain reaction, followed by hybridization with a HSV-specific DNA probe. Herpes simplex virus type 1 and type 2 DNA products were distinguished by digestion with restriction enzymes and analysis by gel electrophoresis. Anti-HSV antibodies in cerebrospinal fluid were detected by immunoblot. Results: The patients had 3 to 9 attacks (mean, 4.6 attacks) of benign recurrent lymphocytic meningitis during periods ranging from 2 to 21 years (mean, 8.4 years). Three of 13 patients had known recurrent genital herpes. Cerebrospinal fluid analysis showed 48 to 1600 cells/µL, glucose levels of more than 2.22 mmol/L (40 mg/dL), and protein levels of 41 to 240 mg/dL (0.41 to 2.4 g/L). Herpes simplex virus DNA and anti-HSV antibodies were detected in cerebrospinal fluid samples in 11 of 13 patients (84.6%; 95% CI, 55% to 98%). Ten of these 11 patients had HSV type 2 DNA and HSV type 2 antibodies. One patient had HSV type 1 DNA and HSV type 1 antibodies in the cerebrospinal fluid. The remaining two patients had only anti-HSV type 2 antibodies. Conclusions: Herpes simplex virus, predominantly HSV type 2, was the major agent causing benign recurrent lymphocytic meningitis that met our specified diagnostic criteria.
Roche denies claims it sacked employee for “whistle blowing”
Authors: Madeleine Brettingham
Journal: BMJ (2006)

<h3>Abstract</h3> <h3>Objective</h3> There is now a substantial body of evidence linking the baseline level of heart rate variability (HRV) with the magnitude of stress-induced reduction in respiratory sinus arrhythmia. However, it remains to be proved to what extent these interindividual differences in stress responses may be attributed to the statistical phenomenon of regression to the mean (RTM). We sought to test the hypothesis that the statistical artifact RTM explains part of the baseline effect. <h3>Approach</h3> Heart rate recording was carried out in 1,156 volunteers. To obtain an estimate of the stress response, 148 persons were randomly selected. Participants were monitored on a rest day and just before an academic examination for state anxiety and HRV. Participants were divided into quartiles according to baseline HRV levels and were compared for response to academic stress. <h3>Main results</h3> We observed a significant reduction in HRV in subjects with a high baseline HRV (&gt; 75th percentile), while a significant increase was found in the group with low baseline HRV. Regression analysis demonstrated that the value of baseline HRV correlated with the magnitude of stress reaction consistent with the RTM model. Baseline-adjusted ANCOVA does not reveal significant intergroup differences in the changes in heart rate (HR) and HRV from rest to exam. RTM-adjusted estimates confirmed an exam effect for HR and HRV. <h3>Significance</h3> The results of our study strongly support RTM as the source of variability of stress-related changes in HRV.
Inhaled Ethyl Nitrite Prevents Hyperoxia-impaired Postnatal Alveolar Development in Newborn Rats
Authors: Richard L. Auten, Stanley N. Mason, Mary H. Whorton, William R. Lampe, W. Michael Foster, Ronald N. Goldberg, Bo Li, Jonathan S. Stamler, Kathryn M. Auten
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Inhaled nitric oxide (NO) has been used to prevent bronchopulmonary dysplasia, but with variable results. Ethyl nitrite (ENO) forms S-nitrosothiols more readily than does NO, and resists higher-order nitrogen oxide formation. Because S-nitrosylation is a key pathway mediating many NO biological effects, treatment with inhaled ENO may better protect postnatal lung development from oxidative stress than NO.To compare inhaled NO and ENO on hyperoxia-impaired postnatal lung development.We treated newborn rats beginning at birth to air or 95% O(2) +/- 0.2-20.0 ppm ENO for 8 days, or to 10 ppm NO for 8 days. Pups treated with the optimum ENO dose, 10 ppm, and pups treated with 10 ppm NO were recovered in room air for 6 more days.ENO and NO partly prevented 95% O(2)-induced airway neutrophil influx in lavage, but ENO had a greater effect than did NO in prevention of lung myeloperoxidase accumulation, and in expression of cytokine-induced neutrophil chemoattractant-1. Treatment with 10 ppm ENO, but not NO, for 8 days followed by recovery in air for 6 days prevented 95% O(2)-induced impairments of body weight, lung compliance, and alveolar development.Inhaled ENO conferred protection superior to inhaled NO against hyperoxia-induced inflammation. ENO prevented hyperoxia impairments of lung compliance and postnatal alveolar development in newborn rats.
Abstract 2757: Characterization of the glucuronidation of the major nicotine metabolite, 3’-hydroxycotinine: Potential role for knock-out polymorphisms in UGTs 2B17 and 2B10
Authors: Gang Chen, Nino E. Giambrone, Joshua E. Muscat, Philip Lazarus
Journal: Cancer Research (2011)

Abstract 3’-Hydroxycotinine (3HC) and its glucuronide (3HC-Gluc) conjugate are major nicotine metabolites excreted in the urine of smokers and other tobacco or nicotine users. Previous studies have demonstrated that human liver microsomes (HLM) were active in catalyzing the formation of both 3HC-O-Gluc and 3HC-N-Gluc. While not all human UDP-glucuronosyltransferases (UGTs) were previously screened, UGTs 2B7, 1A9, 2B4 and 2B15 were shown to be active in the formation of 3HC-O-Gluc and UGT1A4 active in 3HC-N-Gluc formation. In the present study, all known human UGTs except for UGT2B28 were screened for glucuronidation activity against 3HC. Homogenates from cell lines over-expressing UGTs 2B17 and 2B10 exhibited the highest O- and N-glucuronidation activities, respectively for the UGTs tested. Kinetic analysis for the formation of 3HC-O-Gluc demonstrated that the KM for UGT2B17 is 3.7- and 4.2-fold lower than that observed for UGTs 1A9 (p&amp;lt;0.005) and 2B7 (p&amp;lt;0.005); the KM of 3HC-N-Gluc formation was 4.4-fold lower (p&amp;lt;0.05) for UGT2B10 than that observed for UGT1A4. Kinetic analysis demonstrated that HLM from subjects exhibiting the homozygous null UGT2B17 deletion [UGT2B17 (*2/*2)] exhibited a KM for 3HC-O-Gluc formation that was 3.1-fold higher (p&amp;lt;0.001) than that observed in HLM from subjects exhibiting the wild-type UGT2B17(*1/*1) genotype. The KM of 15.6 μM for 3HC-O-Gluc formation in UGT2B17 (*2/*2) HLM was close to that observed for UGT2B17 (8.3 μM). 3HC-N-Gluc formation activity was decreased by 91% (p&amp;lt;0.001) in HLM from subjects with the UGT2B10(*2/*2) knock-out genotype and 39% (p&amp;lt;0.001) in HLM from subjects with the UGT2B10(*1/*2) genotype as compared to that observed for UGT2B10(*1/*1) HLMs. The KM of 13 μM for 3HC-N-Gluc formation in UGT2B10 (*1/*1) HLM (n=6) was close to that observed for UGT2B10 (13 μM). These results demonstrate that UGTs 2B17 and 2B10 play key roles in the hepatic glucuronidation of 3HC and that functional polymorphisms in UGT2B17 and UGT2B10 are associated with significantly reduced glucuronidation activities against 3HC in HLM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2757. doi:10.1158/1538-7445.AM2011-2757