tbuckley/cabot-search huggingface dataset:
Isoniazid resistant tuberculosis in a school outbreak: the protective effect of BCG
Authors: A Shannon, P Kelly, M Lucey, M Cooney, P Corcoran, L Clancy
Journal: European Respiratory Journal (1991)

An outbreak of isoniazid resistant tuberculosis occurred in a large second level school. A total of 1,160 teenage pupils were at risk. Nineteen cases of tuberculosis were diagnosed, 15 were students, 9 of whom were among 251 non-vaccinated students and 6 among 909 vaccinated students. Two cases of miliary tuberculosis, one of whom also had tuberculous (TB) meningitis, occurred in the non-vaccinated group. The number of children with Heaf grade +3 or +4 was significantly greater among children who had been given Bacille Calmette-Guérin (BCG) vaccination (8 vs 4.4%). This suggests a boosting effect on the response in vaccinated children. The protective effect of neonatal BCG vaccination in this school outbreak suggests that it provides significant protection against tuberculosis lasting into adolescence.
Late onset spondylarthropathy: clinical and biological comparison with early onset patients
Authors: D. Caplanne, F. Tubach, J. M. Le Parc
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To compare the clinical, radiological, and biological profile of patients presenting late onset spondylarthropathy (LOSPA) with patients with early onset spondylarthropathy (EOSPA). <h3>METHODS</h3> During the period April 1987 to April 1995 a retrospective chart review of inpatients and outpatients identified eight patients with LOSPA. They were matched with 32 patients with EOSPA examined during the same period of time. Clinical, radiological, and biological signs were compared. All patients fulfilled Amor criteria for spondylarthropathy. <h3>RESULTS</h3> Mean age of patients with LOSPA was 65.1 years (range 58-72), and 26.6 years (range 11-40) in patients with EOSPA. The sex ratio (female/male) was 5/3 in LOSPA and 9/23 in EOSPA (p = 0.007). Patients with LOSPA had more significantly cervical and dorsal pain (p = 0.002, p = 0.02 respectively), anterior chest wall involvement (p = 0.04), number of peripheral arthritis (p = 0.04), aseptic osteitis (p = 0.004), and systemic symptoms : fever, fatigue, weight loss (p = 0.04). Mean (SD) erythrocyte sedimentation rate was 87 (24) in LOSPA and 24 (35) in EOSPA patients (p = 0.001). Inflammatory bowel disease was diagnosed in three patients with EOSPA. A definite family history of SPA was found in 50% of patients with LOSPA and in 31% of patients with EOSPA. A clear response to NSAID was obtained in 62% of LOSPA patients and in 90.6% of EOSPA patients (p = 0.05). Three LOSPA patients (two with Crohn’s disease) not responding to NSAID were successfully treated with prednisone. <h3>CONCLUSION</h3> The onset of spondylarthropathy is uncommon after 55 years. Patients with LOSPA, according to accepted international criteria present a different clinical and biological profile when compared with younger patients. These results suggests that age may influence the presentation of SPA at onset.
Pancreatic toxic effects associated with co-administration of didanosine and tenofovir in HIV-infected adults
Authors: Esteban Martínez, Ana Milinkovic, Elisa de Lazzari, Giovanni Ravasi, L Blanco José, Maria Larrousse, Josep Mallolas, Felipe García, José M Miró, José M Gatell
Journal: The Lancet (2004)
IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction
Authors: Stéphanie Bibert, Thierry Roger, Thierry Calandra, Murielle Bochud, Andreas Cerny, Nasser Semmo, François H.T. Duong, Tilman Gerlach, Raffaele Malinverni, Darius Moradpour, Francesco Negro, Beat Müllhaupt, Pierre-Yves Bochud
Journal: The Journal of Experimental Medicine (2013)

Approximately 3% of the world population is chronically infected with the hepatitis C virus (HCV), with potential development of cirrhosis and hepatocellular carcinoma. Despite the availability of new antiviral agents, treatment remains suboptimal. Genome-wide association studies (GWAS) identified rs12979860, a polymorphism nearby IL28B, as an important predictor of HCV clearance. We report the identification of a novel TT/-G polymorphism in the CpG region upstream of IL28B, which is a better predictor of HCV clearance than rs12979860. By using peripheral blood mononuclear cells (PBMCs) from individuals carrying different allelic combinations of the TT/-G and rs12979860 polymorphisms, we show that induction of IL28B and IFN-γ–inducible protein 10 (IP-10) mRNA relies on TT/-G, but not rs12979860, making TT/-G the only functional variant identified so far. This novel step in understanding the genetic regulation of IL28B may have important implications for clinical practice, as the use of TT/G genotyping instead of rs12979860 would improve patient management.
Is microdialysis useful for early detection of acute rejection after kidney transplantation?
Authors: Hamidreza Fonouni, Mohammad Golriz, Ali Majlesara, Alireza Faridar, Majid Esmaeilzadeh, Parvin Jarahian, Morva Tahmasbi Rad, Mohammadreza Hafezi, Camelia Garoussi, Stephan Macher-Goeppinger, Thomas Longerich, Berk Orakcioglu, Oliver W. Sakowitz, Arianeb Mehrabi
Journal: International Journal of Surgery (2015)
Suicide Risk in Relation to Socioeconomic, Demographic, Psychiatric, and Familial Factors: A National Register–Based Study of All Suicides in Denmark, 1981–1997
Authors: Ping Qin, Esben Agerbo, Preben Bo Mortensen
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Suicide risk was addressed in relation to the joint effect of factors regarding family structure, socioeconomics, demographics, mental illness, and family history of suicide and mental illness, as well as gender differences in risk factors. METHOD: Data were drawn from four national Danish longitudinal registers. Subjects were all 21,169 persons who committed suicide in 1981–1997 and 423,128 live comparison subjects matched for age, gender, and calendar time of suicide by using a nested case-control design. The effect of risk factors was estimated through conditional logistic regression. The interaction of gender with the risk factors was examined by using the log likelihood ratio test. The population attributable risk was calculated. RESULTS: Of the risk factors examined in the study, a history of hospitalization for psychiatric disorder was associated with the highest odds ratio and the highest attributable risk for suicide. Cohabiting or single marital status, unemployment, low income, retirement, disability, sickness-related absence from work, and a family history of suicide and/or psychiatric disorders were also significant risk factors for suicide. Moreover, these factors had different effects in male and female subjects. A psychiatric disorder was more likely to increase suicide risk in female than in male subjects. Being single was associated with higher suicide risk in male subjects, and having a young child with lower suicide risk in female subjects. Unemployment and low income had stronger effects on suicide in male subjects. Living in an urban area was associated with higher suicide risk in female subjects and a lower risk in male subjects. A family history of suicide raised suicide risk slightly more in female than in male subjects. CONCLUSIONS: Suicide risk is strongly associated with mental illness, unemployment, low income, marital status, and family history of suicide. The effect of most risk factors differs significantly by gender.
The adaptive imbalance in base excision–repair enzymes generates microsatellite instability in chronic inflammation
Authors: Lorne J. Hofseth, Mohammed A. Khan, Mark Ambrose, Olga Nikolayeva, Meng Xu-Welliver, Maria Kartalou, S. Perwez Hussain, Richard B. Roth, Xiaoling Zhou, Leah E. Mechanic, Irit Zurer, Varda Rotter, Leona D. Samson, Curtis C. Harris
Journal: Journal of Clinical Investigation (2003)

Chronic infection and associated inflammation are key contributors to human carcinogenesis. Ulcerative colitis (UC) is an oxyradical overload disease and is characterized by free radical stress and colon cancer proneness. Here we examined tissues from noncancerous colons of ulcerative colitis patients to determine (a) the activity of two base excision-repair enzymes, AAG, the major 3-methyladenine DNA glycosylase, and APE1, the major apurinic site endonuclease; and (b) the prevalence of microsatellite instability (MSI). AAG and APE1 were significantly increased in UC colon epithelium undergoing elevated inflammation and MSI was positively correlated with their imbalanced enzymatic activities. These latter results were supported by mechanistic studies using yeast and human cell models in which overexpression of AAG and/or APE1 was associated with frameshift mutations and MSI. Our results are consistent with the hypothesis that the adaptive and imbalanced increase in AAG and APE1 is a novel mechanism contributing to MSI in patients with UC and may extend to chronic inflammatory or other diseases with MSI of unknown etiology.
Immunotherapy Against HPV16/18 Generates Potent T <sub>H</sub> 1 and Cytotoxic Cellular Immune Responses
Authors: Mark L. Bagarazzi, Jian Yan, Matthew P. Morrow, Xuefei Shen, R. Lamar Parker, Jessica C. Lee, Mary Giffear, Panyupa Pankhong, Amir S. Khan, Kate E. Broderick, Christine Knott, Feng Lin, Jean D. Boyer, Ruxandra Draghia-Akli, C. Jo White, J. Joseph Kim, David B. Weiner, Niranjan Y. Sardesai
Journal: Science Translational Medicine (2012)

CD8 + T cells with cytolytic activity are induced after therapeutic human papillomavirus vaccination in humans.
Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies
Authors: Nicola A Hanania, Michael Noonan, Jonathan Corren, Phillip Korenblat, Yanan Zheng, Saloumeh K Fischer, Melissa Cheu, Wendy S Putnam, Elaine Murray, Heleen Scheerens, Cecile TJ Holweg, Romeo Maciuca, Sarah Gray, Ramona Doyle, Dana McClintock, Julie Olsson, John G Matthews, Karl Yen
Journal: Thorax (2015)

Introduction In a subset of patients with asthma, standard-of-care treatment does not achieve disease control, highlighting the need for novel therapeutic approaches. Lebrikizumab is a humanised, monoclonal antibody that binds to and blocks interleukin-13 activity. Methods LUTE and VERSE were replicate, randomised, double-blind, placebo-controlled studies, evaluating multiple doses of lebrikizumab in patients with uncontrolled asthma despite the use of medium-to-high-dose inhaled corticosteroid and a second controller. Patients received lebrikizumab 37.5, 125, 250 mg or placebo subcutaneously every four weeks. The primary endpoint was the rate of asthma exacerbations during the placebo-controlled period. Analyses were performed on prespecified subgroups based on baseline serum periostin levels. Following the discovery of a host-cell impurity in the study drug material, protocols were amended to convert from phase III to phase IIb. Subsequently, dosing of study medication was discontinued early as a precautionary measure. The data collected for analysis were from a placebo-controlled period of variable duration and pooled across both studies. Results The median duration of treatment was approximately 24 weeks. Treatment with lebrikizumab reduced the rate of asthma exacerbations, which was more pronounced in the periostin-high patients (all doses: 60% reduction) than in the periostin-low patients (all doses: 5% reduction); no dose–response was evident. Lung function also improved following lebrikizumab treatment, with greatest increase in FEV 1 in periostin-high patients (all doses: 9.1% placebo-adjusted improvement) compared with periostin-low patients (all doses: 2.6% placebo-adjusted improvement). Lebrikizumab was well tolerated and no clinically important safety signals were observed. Conclusions These data are consistent with, and extend, previously published results demonstrating the efficacy of lebrikizumab in improving rate of asthma exacerbations and lung function in patients with moderate-to-severe asthma who remain uncontrolled despite current standard-of-care treatment. Trial registration numbers The LUTE study was registered under NCT01545440 and the VERSE study under NCT01545453 at http://www.clinicaltrials.gov
The Influence of Hyperthyroidism and Hypothyroidism on the β-Adrenergic Responsiveness of the Turkey Erythrocyte
Authors: John P. Bilezikian, John N. Loeb, Donald E. Gammon
Journal: Journal of Clinical Investigation (1979)

The mechanisms responsible for altered adrenergic tone in hyperthyroidism and hypothyroidism are not fully understood. To investigate these mechanisms, the β-adrenergic receptor-cyclic AMP complex of the turkey erythrocyte was studied among groups of normal, hyperthyroid, and hypothyroid turkeys. In erythrocytes obtained from hypothyroid turkeys, there were fewer β-adrenergic receptors than in normal cells as determined by the specific binding of [125I]iodohydroxybenzylpindolol, as well as associated decreases both in catecholamine-responsive adenylate cyclase activity and in cellular cyclic AMP content. In contrast, erythrocytes obtained from hyperthyroid turkeys contained the same number of β-receptors and had the same catecholamine-responsive adenylate cyclase activity as cells from normal birds. Other characteristics of the β-receptors in cells from hyperthyroid birds were indistinguishable from those present in normal erythrocytes. However, within the range of circulating catecholamine concentrations, 5-50 nM, the erythrocytes of the hyperthyroid turkeys generated substantially more cyclic AMP after exposure to isoproterenol than did normal cells. These results suggest that thyroid hormone affects β-receptor-cyclic AMP interrelationships in the turkey erythrocyte by two distinct mechanisms: (a) In hypothyroidism, both β-receptors and catecholamine-dependent cyclic AMP formation are coordinately decreased; (b) in hyperthyroidism, β-receptors are unchanged but there is an amplification of the hormonal signal so that occupation of a given number of receptors at physiological concentrations of catecholamines leads to increased levels of cyclic AMP.
Cricket ball injury: a cause of symptomatic muscle hernia of the leg
Authors: R K Gupta, D Singh, R Kansay, H Singh
Journal: British Journal of Sports Medicine (2008)

A case of symptomatic muscle hernia of the leg in a provincial cricketer caused by a cricket ball injury is presented. It was diagnosed clinically and treated with a limited fasciotomy. However, delay in the diagnosis and treatment ended the professional career of the player. An awareness of the condition and a high index of suspicion are required to treat this condition in time.
Molecular Determinants of Stereoselective Bupivacaine Block of hKv1.5 Channels
Authors: Laura Franqueza, Mónica Longobardo, Javier Vicente, Eva Delpón, Michael M. Tamkun, Juan Tamargo, Dirk J. Snyders, Carmen Valenzuela
Journal: Circulation Research (1997)

Abstract Enantiomers of local anesthetics are useful probes of ion channel structure that can reveal three-dimensional relations for drug binding in the channel pore and may have important clinical consequences. Bupivacaine block of open hKv1.5 channels is stereoselective, with the R (+)-enantiomer being 7-fold more potent than the S (−)-enantiomer ( K d =4.1 μmol/L versus 27.3 μmol/L). Using whole-cell voltage clamp of hKv1.5 channels and site-directed mutants stably expressed in Ltk − cells, we have identified a set of amino acids that determine the stereoselectivity of bupivacaine block. Replacement of threonine 505 by hydrophobic amino acids (isoleucine, valine, or alanine) abolished stereoselective block, whereas a serine substitution preserved it [ K d =60 μmol/L and 7.4 μmol/L for S (−)- and R (+)-bupivacaine, respectively]. A similar substitution at the internal tetraethylammonium binding site (T477S) reduced the affinity for both enantiomers similarly, thus preserving the stereoselectivity [ K d =45.5 μmol/L and 7.8 μmol/L for S (−)- and R (+)-bupivacaine, respectively]. Replacement of L508 or V512 by a methionine (L508M and V512M) abolished stereoselective block, whereas substitution of V512 by an alanine (V512A) preserved it. Block of Kv2.1 channels, which carry valine, leucine, and isoleucine residues at T505, L508, and V512 equivalent sites, respectively, was not stereoselective [ K d =8.3 μmol/L and 13 μmol/L for S (−)- and R (+)-bupivacaine, respectively]. These results suggest that (1) the bupivacaine binding site is located in the inner mouth of the pore, (2) stereoselective block displays subfamily selectivity, and (3) a polar interaction with T505 combined with hydrophobic interactions with L508 and V512 are required for stereoselective block.
Paracrine sonic hedgehog signalling by prostate cancer cells induces osteoblast differentiation
Authors: Samantha M Zunich, Taneka Douglas, Maria Valdovinos, Tiffany Chang, Wade Bushman, David Walterhouse, Philip Iannaccone, Marilyn LG Lamm
Journal: Molecular Cancer (2009)

Abstract Background Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis. The mechanism through which Shh signalling could promote metastasis in bone, the most common site for prostate carcinoma metastasis, has not yet been investigated. The present study determined the effect of Shh signalling between prostate cancer cells and pre-osteoblasts on osteoblast differentiation, a requisite process for new bone formation that characterizes prostate carcinoma metastasis. Results LNCaP human prostate cancer cells modified to overexpress Shh (designated LNShh cells) and MC3T3 mouse pre-osteoblasts were maintained as mixed populations within the same culture chamber. In this non-conventional mixed culture system, LNShh cells upregulated the expression of Shh target genes Gli1 and Patched 1 ( Ptc1 ) in MC3T3 cells and this was inhibited by cyclopamine, a specific chemical inhibitor of hedgehog signalling. Concomitantly, MC3T3 cells exhibited time-dependent decreased cell proliferation, upregulated alkaline phosphatase Akp2 gene expression, and increased alkaline phosphatase activity indicative of early phase osteoblast differentiation. LNShh cell-induced differentiation was inhibited in MC3T3 cells stably transfected with a dominant negative form of Gli1, a transcription factor that mediates Shh signalling. Interestingly, LNShh cells did not significantly increase the endogenous expression of the osteoblast differentiation transcription factor Runx2 and its target genes osteocalcin and osteopontin . Consistent with these results, exogenous Shh peptide did not upregulate Runx2 expression in MC3T3 cells. However, Runx2 levels were increased in MC3T3 cells by ascorbic acid, a known stimulator of osteoblast differentiation. Conclusion Altogether, these data demonstrate that Shh-expressing prostate cancer cells can directly and specifically induce differentiation in pre-osteoblasts via a Gli1-dependent mechanism that does not require transcriptional upregulation of Runx2 . Paracrine activation of the Shh pathway in osteoblast progenitors and subsequent induction of osteoblast differentiation could be a mechanism through which high levels of Shh expression in prostate carcinoma contribute to bone metastasis. Targeting of paracrine Shh signalling may provide an effective therapeutic strategy against prostate carcinoma metastasis in bone.
Risks of conservative management in women with ovarian endometriomas undergoing IVF
Authors: Edgardo Somigliana, Laura Benaglia, Alessio Paffoni, Andrea Busnelli, Paola Vigano, Paolo Vercellini
Journal: Human Reproduction Update (2015)

BACKGROUNDClassical surgical management of endometriotic ovarian cysts using the laparoscopic stripping technique has been recently questioned because of the surgical-related injury to the ovarian reserve. Accordingly, available guidelines suggest that endometriomas with a mean diameter below 4 cm should not be systematically removed before IVF procedures. However, conservative management may have some potential drawbacks and risks. The presence of the endometrioma may theoretically interfere with ovarian responsiveness to hyperstimulation and oocyte competence, the retrieval of the oocytes may be more difficult and risky, the disease may progress during the procedure, pregnancy outcome may be affected and there is the risk of missing occult malignancies with cancer development later in life. In the present review, we aimed at assessing whether these risks do exist and, if so, at estimating their clinical relevance.
Locally Recurrent, Previously Irradiated Head and Neck Cancer: Concurrent Re-Irradiation and Chemotherapy, or Chemotherapy Alone?
Authors: Stuart J. Wong, Mitchell Machtay, Yi Li
Journal: Journal of Clinical Oncology (2006)

Patients with locally recurrent head and neck cancer previously treated with radiation have a poor prognosis. Administration of a second course of radiation to tissues within a previous radiation portal, has been traditionally considered unsafe. Survival rates of highly selected patients treated with concurrent chemotherapy and re-irradiation may be as high as 25% at 2 years--exceeding the outcome of matched historical controls treated with chemotherapy alone (10%). However, many questions exist regarding the use of re-irradiation. Uncertainty exists over the criteria for selecting patients who are most appropriate for treatment with re-irradiation. Even greater concern exists regarding toxicity and functional sequelae associated with the use of re-irradiation. Whether the benefits of re-irradiation on locoregional disease control and survival outweigh its potentially severe and life-threatening adverse effects is not clear. In this review, we will discuss re-irradiation and other treatment options for squamous cell carcinoma patients with previously irradiated, locoregional recurrent or second primary tumors in the head and neck, and describe a recently initiated randomized trial comparing chemotherapy plus re-irradiation with chemotherapy.