tbuckley/cabot-search huggingface dataset:
Lung function abnormalities in patients infected with the human immunodeficiency virus with and without overt pneumonitis.
Authors: R J Shaw, C Roussak, S M Forster, J R Harris, A J Pinching, D M Mitchell
Journal: Thorax (1988)

Pulmonary function was measured in 169 male patients seropositive for the human immunodeficiency virus (HIV). The transfer factor for carbon monoxide (TLCO) in symptom free patients and patients with persistent generalised lymphadenopathy was normal (greater than 83% of predicted values). Patients with the AIDS related complex, non-pulmonary Kaposi sarcoma, and non-pulmonary non-Kaposi sarcoma AIDS (that is, opportunist infections affecting other organs) had lower mean values for TLCO (77%, 70%, and 70% of predicted respectively). These values were significantly lower than values for symptom free patients. Lower mean values of 50% and 63% predicted TLCO were observed in patients during the acute and recovery phases of Pneumocystis carinii pneumonia. TLCO was also low in patients with lung mycobacterial infection and in a patient with lung Kaposi sarcoma. Forced expiratory volume in one second, peak expiratory flow, and maximal expiratory flow at 50% of vital capacity were significantly reduced only in patients with acute pneumocystis pneumonia. This study shows that abnormalities in the results of pulmonary function tests, particularly TLCO, although greatest in patients with pulmonary complications of AIDS, are also present in patients with AIDS but without other evidence of pulmonary disease, and in patients with the AIDS related complex. The predictive and prognostic implications of these findings require further investigation.
Bell pepper is involved in the latex-fruit syndrome based on cross-reactivities to Hev b 2, Hev b 8 and a 30 kDa protein
Authors: Stefan Wagner, Martin Grob, Christine Hafner, Brunello Wuethrich, Erika Jensen-Jarolim, Otto Scheiner, Heimo Breiteneder
Journal: Journal of Allergy and Clinical Immunology (2002)
Switching from NSAIDs to paracetamol: a series of n of 1 trials for individual patients with osteoarthritis
Authors: A C M Wegman
Journal: Annals of the Rheumatic Diseases (2003)

To investigate for individual patients who have been using NSAIDs regularly, whether paracetamol is as effective as non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of pain and disability related to osteoarthritis of the hip or knee.A series of n of 1 trials were conducted in general practices in Amsterdam and the surrounding area. Each patient was his or her own control and received five pairs of treatments comprising two weeks of an NSAID and two weeks of paracetamol. For each pair, the order of treatments was randomised. Outcome measures were severity of individual main complaints, intensity of pain, satisfaction with drugs, function test, and side effects.Thirteen patients were selected. Six patients did not complete the study. For five patients completing the study little or no difference was found between NSAIDs and paracetamol, for one patient the results favoured the NSAID, and for one patient there was no association between outcome and type of drug. It was recommended that six patients changed to paracetamol; the others continued with NSAIDs. Three months after the end of the study, four of the six patients for whom paracetamol had been recommended were taking NSAIDs for practical reasons or perceived lack of efficacy.The results of the n of 1 trials varied across patients. n of 1 trials can be used to investigate which treatment is best for any specific person, thus avoiding unnecessary prolonged treatment with NSAIDs. However, practical reasons may cause patients to switch from NSAIDs to paracetamol or not.
Telomere shortening of epithelial cells characterises the adenoma-carcinoma transition of human colorectal cancer
Authors: R R Plentz
Journal: Gut (2003)

<b>Background and aims:</b> Chromosomal instability is one of the most consistent markers of sporadic colorectal cancer in humans. There is growing evidence that telomere shortening is one of the mechanisms leading to chromosomal instability and cancer initiation. <b>Methods:</b> To test this hypothesis, the telomere length of colorectal epithelial cells and cells from connective tissue was determined at the adenoma-carcinoma transition at the cellular level by quantitative fluorescence in situ hybridisation. <b>Results:</b> Our study showed that the telomere fluorescence intensity of epithelial cells was significantly weaker at the earliest morphologically definable stage of carcinoma—high grade dysplasia with minimal invasive growth—compared with the surrounding adenoma. In contrast, cells from connective tissue had a similar telomere signal intensity at the carcinoma stage compared with the adenoma, and in turn cells from connective tissue had overall significantly stronger telomere fluorescence signals compared with epithelial cells. <b>Conclusions:</b> These results demonstrate that short telomeres of epithelial cells characterise the adenoma-carcinoma transition during human colorectal carcinogenesis, suggesting that carcinomas arise from cells with critical short telomeres within the adenoma. Since the adenoma-carcinoma transition in colorectal cancer is characterised by an increase in chromosomal instability and anaphase bridges, our data support the hypothesis that short telomeres initiate colorectal cancer by induction of chromosomal instability.
Association of Autistic-Like and Internalizing Traits During Childhood: A Longitudinal Twin Study
Authors: Victoria Hallett, Angelica Ronald, Fruhling Rijsdijk, Francesca Happé
Journal: American Journal of Psychiatry (2010)

Objective Children with autism spectrum disorders often experience severe anxiety and depression, yet the explanation for this association remains unclear. The authors examined the longitudinal relationship between autistic-like and internalizing traits across middle to late childhood in a population-representative twin sample. Method Participants were approximately 6,000 twin pairs born in England and Wales from 1994 to 1996. Parental reports of autistic-like and internalizing traits were analyzed at ages 7 and 8 (timepoint 1) and again at age 12 (timepoint 2). The direction and etiology of the associations between these traits were examined within a cross-lagged design. Results Findings revealed an asymmetric bidirectional association between autistic-like and internalizing traits over time. Autistic-like traits at age 7 made a modest but significant contribution to the presence of internalizing traits at age 12. Earlier internalizing traits also influenced the development of later autistic-like traits, although this association was approximately one-half the magnitude. While both traits were moderately to highly heritable, they were largely independent with regard to their genetic influences. Stronger associations were found between the modest shared environmental influences on each trait. Of note, it was autistic-like communication difficulties, rather than social deficits, that made a significant contribution to later internalizing traits. Conclusions The association between autistic-like and internalizing traits was attributable to reciprocal processes occurring across childhood, suggesting that these traits may serve to exacerbate each other over time. Autistic-like communication difficulties had the most notable impact. This association must now be explored within samples of children with diagnosed autism spectrum disorders and internalizing disorders, since this may help to inform the best timing and targeting of clinical intervention.
miR-150 as a potential biomarker associated with prognosis and therapeutic outcome in colorectal cancer
Authors: Yanlei Ma, Peng Zhang, Feng Wang, Huizhen Zhang, Jianjun Yang, Jiayuan Peng, Weijie Liu, Huanlong Qin
Journal: Gut (2011)

<h3>Background</h3> MicroRNAs (miRNA) have potential as prognostic biomarkers and therapeutic targets in cancer. A study was undertaken to investigate the association between miRNA expression patterns and the prognosis and therapeutic outcome of colorectal cancer (CRC). <h3>Methods</h3> miRNA expression profiling in tumour, adenoma and normal colorectal tissues was performed to identify tumour-related miRNAs in the course of colorectal malignant changes. Quantitative reverse transcription PCR (qRT-PCR) assays were used to measure tumour-related miRNA and to assess its association with survival and response to adjuvant chemotherapy in 239 patients. In addition, to validate the findings, associations of the tumour-related miRNA with clinical characteristics of CRC were analysed in 185 patients by in situ hybridisation (ISH) analysis. <h3>Results</h3> Only one miR-150 was found to show a decrease in expression levels in the three tissue groups (normal, adenoma and cancer tissue) in parallel with increasing carcinogenesis of the colorectal tissue. In both ISH and qRT-PCR analysis, tumour tissue had reduced levels of miR-150 expression compared with paired non-cancerous tissue, which indicated that the levels of miR-150 expression were associated with CRC. Moreover, patients whose tumours had low miR-150 expression had shorter survival and a worse response to adjuvant chemotherapy than patients whose tumours had high miRNA expression. <h3>Conclusions</h3> The miR-150 expression status of patients with CRC is associated with survival and response to adjuvant chemotherapy. It is suggested that miR-150 should be considered as a potential biomarker associated with the prognosis and therapeutic outcome in CRC.
Recent advances: Telemedicine
Authors: R. Wootton
Journal: BMJ (2001)

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p27Kip1 controls cytokinesis via the regulation of citron kinase activation
Authors: Murielle P. Serres, Uta Kossatz, Yong Chi, James M. Roberts, Nisar P. Malek, Arnaud Besson
Journal: Journal of Clinical Investigation (2012)

p27(Kip1) (p27) acts as a tumor suppressor by inhibiting cyclin-cyclin-dependent kinase (cyclin-CDK) activity. However, mice expressing a form of p27 that is unable to bind or inhibit cyclin-CDK complexes (p27(CK-)) have increased incidence of tumor development as compared with wild-type and p27(-/-) mice, revealing an oncogenic role for p27. Here, we identified a phenotype of multinucleation and polyploidy in p27(CK-) mice not present in p27(-/-) animals, suggesting a role for p27 in G2/M that is independent of cyclin-CDK regulation. Further analysis revealed that p27(CK-) expression caused a cytokinesis and abscission defect in mouse embryonic fibroblasts. We identified the Rho effector citron kinase (citron-K) as a p27-interacting protein in vitro and in vivo and found that p27 and citron-K colocalized at the contractile ring and mid-body during telophase and cytokinesis. Moreover, overexpression of the minimal p27-binding domain of citron-K was sufficient to rescue the phenotype caused by p27(CK-). Conversely, expression of a mutant p27(CK-) unable to bind citron-K did not induce multinucleation. Finally, by binding to citron-K, p27 prevented the interaction of citron-K with its activator RhoA. Taken together, these data suggest a role for p27 during cytokinesis via the regulation of citron-K activity.
The Chaperonin Genes of Jakobid and Jakobid-Like Flagellates: Implications for Eukaryotic Evolution
Authors: John M. Archibald, Charles J. O'Kelly, W. Ford Doolittle
Journal: Molecular Biology and Evolution (2002)

The jakobids are free-living mitochondriate protists that share ultrastructural features with certain amitochondriate groups and possess the most bacterial-like mitochondrial genomes described thus far. Jakobids belong to a diverse group of mitochondriate and amitochondriate eukaryotes, the excavate taxa. The relationships among the various excavate taxa and their relationships to other putative deep-branching protist groups are largely unknown. With the hope of clarifying these issues, we have isolated the cytosolic chaperonin CCTalpha gene from the jakobid Reclinomonas americana (strains 50394 and 50283), the jakobid-like malawimonad Malawimonas jakobiformis, two heteroloboseans (Acrasis rosea and Naegleria gruberi), a euglenozoan (Trypanosoma brucei), and a parabasalid (Monocercomonas sp.). We also amplified the CCTdelta gene from M. jakobiformis. The Reclinomonas and Malawimonas sequences presented here are among the first nuclear protein-coding genes to be described from these organisms. Unlike other putative early diverging protist lineages, a high density of spliceosomal introns was found in the jakobid and malawimonad CCTs—similar to that observed in vertebrate protein-coding genes. An analysis of intron positions in CCT genes from protists, plants, animals, and fungi suggests that many of the intron-sparse or intron-lacking protist lineages may not be primitively so but have lost spliceosomal introns during their evolutionary history. In phylogenetic trees constructed from CCTalpha protein sequences, R. americana (but not M. jakobiformis) shows a weak but consistent affinity for the Heterolobosea and Euglenozoa.
Antioxidants can increase melanoma metastasis in mice
Authors: Kristell Le Gal, Mohamed X. Ibrahim, Clotilde Wiel, Volkan I. Sayin, Murali K. Akula, Christin Karlsson, Martin G. Dalin, Levent M. Akyürek, Per Lindahl, Jonas Nilsson, Martin O. Bergo
Journal: Science Translational Medicine (2015)

Antioxidants increase migration and invasion of human melanoma cells and accelerate metastasis in an endogenous mouse model of malignant melanoma.
Cholesterol Depletion Impairs Vascular Reactivity to Endothelin-1 by Reducing Store-Operated Ca <sup>2+</sup> Entry Dependent on TRPC1
Authors: Andreas Bergdahl, Maria F. Gomez, Karl Dreja, Shang-Zhong Xu, Mikael Adner, David J. Beech, Jonas Broman, Per Hellstrand, Karl Swärd
Journal: Circulation Research (2003)

The reactivity of the vascular wall to endothelin-1 (ET-1) is influenced by cholesterol, which is of possible importance for the progression of atherosclerosis. To elucidate signaling steps affected, the cholesterol acceptor methyl-β-cyclodextrin (mβcd, 10 mmol/L) was used to manipulate membrane cholesterol and disrupt caveolae in intact rat arteries. In endothelium-denuded caudal artery, contractile responsiveness to 10 nmol/L ET-1 (mediated by the ET A receptor) was reduced by mβcd and increased by cholesterol. Neither ligand binding nor colocalization of ET A and caveolin-1 was affected by mβcd. Ca 2+ inflow via store-operated channels after depletion of intracellular Ca 2+ stores was reduced in mβcd-treated caudal arteries, as shown by Mn 2+ quench rate and intracellular [Ca 2+ ] response. Expression of TRPC1, 3, and 6 was detected by reverse transcriptase–polymerase chain reaction, and colocalization of TRPC1 with caveolin-1 was reduced by mβcd, as seen by immunofluorescence. Part of the contractile response to ET-1 was inhibited by Ni 2+ (0.5 mmol/L) and by a TRPC1 blocking antibody. In the basilar artery, exhibiting less store-operated channel activity than the caudal artery, ET-1–induced contractions were insensitive to the TRPC1 blocking antibody and to mβcd. Increased store-operated channel activity in basilar arteries after organ culture correlated with increased sensitivity of ET-1 contraction to mβcd. These results suggest that cholesterol influences vascular reactivity to ET-1 by affecting the caveolar localization of TRPC1.
AR-Regulated TWEAK-FN14 Pathway Promotes Prostate Cancer Bone Metastasis
Authors: JuanJuan Yin, Yen-Nien Liu, Heather Tillman, Ben Barrett, Stephen Hewitt, Kris Ylaya, Lei Fang, Ross Lake, Eva Corey, Colm Morrissey, Robert Vessella, Kathleen Kelly
Journal: Cancer Research (2014)

Abstract The recurrence of prostate cancer metastases to bone after androgen deprivation therapy is a major clinical challenge. We identified FN14 (TNFRSF12A), a TNF receptor family member, as a factor that promotes prostate cancer bone metastasis. In experimental models, depletion of FN14 inhibited bone metastasis, and FN14 could be functionally reconstituted with IKKβ-dependent, NFκB signaling activation. In human prostate cancer, upregulated FN14 expression was observed in more than half of metastatic samples. In addition, FN14 expression was correlated inversely with androgen receptor (AR) signaling output in clinical samples. Consistent with this, AR binding to the FN14 enhancer decreased expression. We show here that FN14 may be a survival factor in low AR output prostate cancer cells. Our results define one upstream mechanism, via FN14 signaling, through which the NFκB pathway contributes to prostate cancer metastasis and suggest FN14 as a candidate therapeutic and imaging target for castrate-resistant prostate cancers. Cancer Res; 74(16); 4306–17. ©2014 AACR.
PREVENTION OF PERINATALLY TRANSMITTED HEPATITIS B VIRUS INFECTIONS WITH HEPATITIS B IMMUNE GLOBULIN AND HEPATITIS B VACCINE
Authors: R.Palmer Beasley, George CHIN-YUN LEE, Cheng-Hsiung Roan, Lu-Yu Hwang, Chung-Chi Lan, Fu-Yuan Huang, Chiung-Lin Chen
Journal: The Lancet (1983)
Analysis of a Horizontally Transferred Pathway Involved in Vitamin B6 Biosynthesis from the Soybean Cyst Nematode Heterodera glycines
Authors: J. P. Craig, S. Bekal, M. Hudson, L. Domier, T. Niblack, K. N. Lambert
Journal: Molecular Biology and Evolution (2008)

Heterodera glycines is an obligate plant parasite capable of biochemically and developmentally altering its host's cells in order to create a specialized feeding cell. Although the exact mechanism of feeding cell morphogenesis remains a mystery, the nematode's ability to manipulate the plant is thought to be due in part to horizontal gene transfers (HGTs). A bioinformatic screen of the nematode genome has revealed homologues of the genes SNZ and SNO, which comprise a metabolic pathway for the de novo biosynthesis of pyridoxal 5'-phosphate, the active form of vitamin B(6) (VB(6)). Analysis of the 2 genes, HgSNZ and HgSNO, show that they contain nematode-like introns, generate polyadenylated mRNAs, and map to the soybean cyst nematode genetic linkage map, indicating that they are part of the nematode genome. However, gene synteny, protein homology, and phylogenetic evidence suggest prokaryotic origin. This would represent the first case of the HGT of a complete pathway into a nematode or terrestrial animal. VB(6) acts as a cofactor in over 140 different enzymes, and recent studies point toward an important role as a potent quencher of reactive oxygen species. With H. glycines' penchant for acquiring parasitism genes through HGT along with the absence of this pathway in other land-based animals suggests a specific need for VB(6) which may involve the parasite-host interaction.
Variation of Breast Cancer Risk Among BRCA1/2 Carriers
Authors: Colin B. Begg, Robert W. Haile, Åke Borg, Kathleen E. Malone, Patrick Concannon, Duncan C. Thomas, Bryan Langholz, Leslie Bernstein, Jørgen H. Olsen, Charles F. Lynch, Hoda Anton-Culver, Marinela Capanu, Xiaolin Liang, Amanda J. Hummer, Cami Sima, Jonine L. Bernstein
Journal: JAMA (2008)

The risk of breast cancer in BRCA1 and BRCA2 mutation carriers has been examined in many studies, but relatively little attention has been paid to the degree to which the risk may vary among carriers.To determine the extent to which risks for BRCA1 and BRCA2 carriers vary with respect to observable and unobservable characteristics.Probands were identified from a population-based, case-control study (Women's Environmental Cancer and Radiation Epidemiology [WECARE]) of asynchronous contralateral breast cancer conducted during the period of January 2000 to July 2004. Participants previously diagnosed with contralateral breast cancer or unilateral breast cancer were genotyped for mutations in BRCA1 and BRCA2. All participants had their initial breast cancer diagnosed during the period of January 1985 to December 2000, before the age of 55 years.Incidence of breast cancer in first-degree female relatives of the probands was examined and compared on the basis of proband characteristics and on the basis of variation between families.Among the 1394 participants with unilateral breast cancer, 73 (5.2%) were identified as carriers of deleterious mutations (42 with BRCA1 and 31 with BRCA2). Among the 704 participants with contralateral breast cancer, 108 (15.3%) were identified as carriers of deleterious mutations (67 with BRCA1 and 41 with BRCA2). Among relatives of carriers, risk was significantly associated with younger age at diagnosis in the proband (P = .04), and there was a trend toward higher risk for relatives of contralateral breast cancer vs unilateral breast cancer participants (odds ratio, 1.4 [95% confidence interval, 0.8-2.4]; P = .28). In addition, there were significant differences in risk between carrier families after adjusting for these observed characteristics.There exists broad variation in breast cancer risk among carriers of BRCA1 and BRCA2 mutations.
Blood Lead Below 0.48 μmol/L (10 μg/dL) and Mortality Among US Adults
Authors: Andy Menke, Paul Muntner, Vecihi Batuman, Ellen K. Silbergeld, Eliseo Guallar
Journal: Circulation (2006)

Background— Blood lead levels above 0.48 μmol/L (10 μg/dL) in adults have been associated with increased risk of cardiovascular, cancer, and all-cause mortality. The objective of the present study was to determine the association between blood lead levels below 0.48 μmol/L and mortality in the general US population. Methods and Results— Blood lead levels were measured in a nationally representative sample of 13 946 adult participants of the Third National Health and Nutrition Examination Survey recruited in 1988 to 1994 and followed up for up to 12 years for all-cause and cause-specific mortality. The geometric mean blood lead level in study participants was 0.12 μmol/L (2.58 μg/dL). After multivariate adjustment, the hazard ratios (95% CI) for comparisons of participants in the highest tertile of blood lead (≥0.17 μmol/L [≥3.62 μg/dL]) with those in the lowest tertile (&lt;0.09 μmol/L [&lt;1.94 μg/dL]) were 1.25 (1.04 to 1.51; P trend across tertiles=0.002) for all-cause mortality and 1.55 (1.08 to 2.24; P trend across tertiles=0.003) for cardiovascular mortality. Blood lead level was significantly associated with both myocardial infarction and stroke mortality, and the association was evident at levels &gt;0.10 μmol/L (≥2 μg/dL). There was no association between blood lead and cancer mortality in this range of exposure. Conclusions— The association between blood lead levels and increased all-cause and cardiovascular mortality was observed at substantially lower blood lead levels than previously reported. Despite the marked decrease in blood lead levels over the past 3 decades, environmental lead exposures remain a significant determinant of cardiovascular mortality in the general population, constituting a major public health problem.