tbuckley/cabot-search huggingface dataset:
Association of maternal smoking with increased infant oxidative stress at 3 months of age
Authors: P. S Noakes, R. Thomas, C. Lane, T. A Mori, A. E Barden, S. G Devadason, S. L Prescott
Journal: Thorax (2007)

Cigarette smoke is a major source of free radicals and oxidative stress. With a significant proportion of women still smoking during pregnancy, this common and avoidable exposure has the potential to influence infant oxidative status, which is implicated in the increased propensity for airway inflammation and asthma. The aim of this study was to examine the effects of maternal smoking on markers of infant oxidative stress.The level of oxidative stress (using urinary F2-isoprostanes as a marker of lipid peroxidation) was compared in infants of smokers (n = 33) and non-smokers (n = 54) at 3 months of age. These groups were balanced for maternal atopy and socioeconomic status. Infant urinary cotinine levels were also measured as an indicator of early postnatal cigarette smoke exposure.Maternal smoking was associated with significantly higher infant cotinine levels, despite the fact that most smoking mothers (83.8%) claimed not to smoke near their baby. Maternal smoking was associated with significantly higher markers of oxidative stress (F2-isoprostane) at 3 months of age. There was also a positive correlation between urinary F2-isoprostanes and infant urinary cotinine levels.Although this study does not separate the prenatal and postnatal effects of smoking, these findings indicate that environmental tobacco smoke in the early postnatal period adversely affects pro-oxidative/antioxidative status within weeks of life in very early infancy.
Effects of Primary Angioplasty for Acute Myocardial Infarction on Early and Late Infarct Size and Left Ventricular Wall Characteristics
Authors: Timo Baks, Robert-Jan van Geuns, Elena Biagini, Piotr Wielopolski, Nico R. Mollet, Filippo Cademartiri, Willem J. van der Giessen, Gabriel P. Krestin, Patrick W. Serruys, Dirk J. Duncker, Pim J. de Feyter
Journal: Journal of the American College of Cardiology (2005)
Chronic hemolytic anemia due to cold agglutinins
Authors: Robert S. Evans, Elizabeth Turner, Margaret Bingham, Richard Woods
Journal: Journal of Clinical Investigation (1968)

The sera of four patients with chronic hemolytic anemia due to cold agglutinins deposited C′ globulins on normal red cells at 37°C. The circulating cells of the patients were heavily coated with C′ complex and were relatively resistant to C′ hemolysis by cold agglutinin. Such red cells were removed from the patients' circulation at an exponential rate with 51Cr t½ that varied from 7 to 19 days. Normal red cells were removed rapidly by hepatic sequestration during the first hours in the patients' circulation. Thereafter, a slower rate of abnormal destruction occurred which was associated with the accumulation of C′ complexes on the red cell and the development of resistance to C′ hemolysis by cold agglutinin. Normal red cells coated with sufficient C′ complex by action of cold agglutinins in vitro to produce resistance to C′ hemolysis by cold agglutinins demonstrated varying degrees of improved survival during the first hours in the circulation of three of the patients.
Statin Use as a Moderator of Metformin Effect on Risk for Prostate Cancer Among Type 2 Diabetic Patients
Authors: Donna M. Lehman, Carlos Lorenzo, Javier Hernandez, Chen-pin Wang
Journal: Diabetes Care (2012)

Metformin and statins have shown promise for cancer prevention. This study assessed whether the effect of metformin on prostate cancer (PCa) incidence varied by statin use among type 2 diabetic patients.
Nicotine replacement: a new approach to reducing tobacco-related harm
Authors: C Jimenez-Ruiz, M Kunze, KO Fagerstrom
Journal: European Respiratory Journal (1998)

Primary prevention is usually regarded as the most desirable goal in efforts to control tobacco-related diseases. However, this has not been very effective so far; moreover, it would take 30-40 yrs for primary prevention to translate into major health benefits. Modification of tobacco products and/or reduction of tobacco use may also have some impact on tobacco-related diseases. A tobacco dose-dependent risk has been observed in these diseases, including cancer, cardiovascular diseases, chronic nonspecific respiratory disorders, and problems during pregnancy. Reduced smoking (smoking fewer cigarettes, leading to a reduced intake of toxic substances) may be indicated in individuals who: 1) are failing in cessation attempts; 2) want to quit but are unable to do so; and 3) do not want to quit but want to reduce smoking. Studies have shown that nicotine replacement medications may be an untapped source in efforts to reduce smoking. Based on Austrian data, it is estimated that, approximately 10 yrs after implementation, a 1% reduction in smoking could save 14 male lung cancer deaths each year, and a 50% reduction would save 700 male lives. Inclusion of females and other tobacco-related diseases suggest that thousands of lives could be saved if smoking could be reduced by 50%. In the European Union, such a reduction in smoking could save &gt; or = 100,000 lives annually. Even a 1% reduction would save 1,000 lives. In conclusion, reduced smoking should be explored as a valid method of reducing tobacco-related harm in those unwilling or unable to quit smoking.
Comparison of Basal Insulin Added to Oral Agents Versus Twice-Daily Premixed Insulin as Initial Insulin Therapy for Type 2 Diabetes
Authors: Hans U. Janka, Gerd Plewe, Matthew C. Riddle, Christine Kliebe-Frisch, Matthias A. Schweitzer, Hannele Yki-Järvinen
Journal: Diabetes Care (2005)

OBJECTIVE—To compare the efficacy and safety of adding once-daily basal insulin versus switching to twice-daily premixed insulin in type 2 diabetic patients insufficiently controlled by oral antidiabetic agents (OADs). RESEARCH DESIGN AND METHODS—In a 24-week, multinational, multicenter, open, parallel group clinical trial, 371 insulin-naïve patients with poor glycemic control (fasting blood glucose [FBG] ≥120 mg/dl, HbA1c 7.5–10.5%) on OADs (sulfonylurea plus metformin) were randomized to once-daily morning insulin glargine plus glimepiride and metformin (glargine plus OAD) or to 30% regular/70% human NPH insulin (70/30) twice daily without OADs. Insulin dosage was titrated to target FBG ≤100 mg/dl (both insulins) and predinner blood glucose ≤100 mg/dl (70/30 only) using a weekly forced-titration algorithm. RESULTS—Mean HbA1c decrease from baseline was significantly more pronounced (−1.64 vs. −1.31%, P = 0.0003), and more patients reached HbA1c ≤7.0% without confirmed nocturnal hypoglycemia (45.5 vs. 28.6%, P = 0.0013) with glargine plus OAD than with 70/30. Similarly, FBG decrease was greater with glargine plus OAD (adjusted mean difference −17 mg/dl [–0.9 mmol/l], P &amp;lt; 0.0001), and more patients reached target FBG ≤100 mg/dl with glargine plus OAD than with 70/30 (31.6 vs. 15.0%, P = 0.0001). Glargine plus OAD patients had fewer confirmed hypoglycemic episodes than 70/30 patients (mean 4.07 vs. 9.87/patient-year, P &amp;lt; 0.0001). CONCLUSIONS—Initiating insulin treatment by adding basal insulin glargine once daily to glimepiride plus metformin treatment was safer and more effective than beginning twice-daily injections of 70/30 and discontinuing OADs in type 2 diabetic patients inadequately controlled with OADs.
Slightly elevated B‐type natriuretic peptide levels in a non‐heart failure range indicate a worse left ventricular diastolic function in individuals with, as compared with individuals without, type 2 diabetes: the Hoorn Study
Authors: Katja van den Hurk, Marjan Alssema, Otto Kamp, Ronald M. Henry, Coen D. Stehouwer, Michaela Diamant, Frans Boomsma, Rob J. Heine, Giel Nijpels, Walter J. Paulus, Jacqueline M. Dekker
Journal: European Journal of Heart Failure (2010)
In-depth genomic data analyses revealed complex transcriptional and epigenetic dysregulations of BRAF V600E in melanoma
Authors: Xingyi Guo, Yaomin Xu, Zhongming Zhao
Journal: Molecular Cancer (2015)

The recurrent BRAF driver mutation V600E (BRAF (V600E)) is currently one of the most clinically relevant mutations in melanoma. However, the genome-wide transcriptional and epigenetic dysregulations induced by BRAF (V600E) are still unclear. The investigation of this driver mutation's functional consequences is critical to the understanding of tumorigenesis and the development of therapeutic strategies.We performed an integrative analysis of transcriptomic and epigenomic changes disturbed by BRAF (V600E) by comparing the gene expression and methylation profiles of 34 primary cutaneous melanoma tumors harboring BRAF (V600E) with those of 27 BRAF (WT) samples available from The Cancer Genome Atlas (TCGA). A total of 711 significantly differentially expressed genes were identified as putative BRAF (V600E) target genes. Functional enrichment analyses revealed the transcription factor MITF (p < 3.6 × 10(-16)) and growth factor TGFB1 (p < 3.1 × 10(-9)) were the most significantly enriched up-regulators, with MITF being significantly up-regulated, whereas TGFB1 was significantly down-regulated in BRAF (V600E), suggesting that they may mediate tumorigenesis driven by BRAF (V600E). Further investigation using the MITF ChIP-Seq data confirmed that BRAF (V600E) led to an overall increased level of gene expression for the MITF targets. Furthermore, DNA methylation analysis revealed a global DNA methylation loss in BRAF (V600E) relative to BRAF (WT). This might be due to BRAF dysregulation of DNMT3A, which was identified as a potential target with significant down-regulation in BRAF (V600E). Finally, we demonstrated that BRAF (V600E) targets may play essential functional roles in cell growth and proliferation, measured by their effects on melanoma tumor growth using a short hairpin RNA silencing experimental dataset.Our integrative analysis identified a set of BRAF (V600E) target genes. Further analyses suggested a complex mechanism driven by mutation BRAF (V600E) on melanoma tumorigenesis that disturbs specific cancer-related genes, pathways, and methylation modifications.
A comparison of two treatment protocols in the management of exercise-associated postural hypotension: a randomised clinical trial
Authors: Cameron Anley, Timothy Noakes, Malcolm Collins, Martin P Schwellnus
Journal: British Journal of Sports Medicine (2010)

Objective To investigate which of two commonly used treatment protocols for exercise-associated postural hypotension (EAPH) resulted in earlier discharge from the medical facility. Methods This randomised clinical field trial was undertaken at two Ironman Triathlon competitions and one ultra-distance footrace. All collapsed athletes admitted to the medical facilities were considered for the trial. Following clinical assessment and special investigations to confirm the diagnosis of EAPH, 28 athletes were randomly assigned to an oral fluid and Trendelenburg position (OT=14) or an intravenous fluid (IV=14) treatment group. Following admission fluid intake was recorded, and all athletes were assessed clinically (blood pressure, heart rate, level of consciousness) every 15 min until discharge criteria were met. The main measure of outcome was the time to discharge (min). Results On admission, subjects in the OT and IV groups were similar with respect to age, systolic blood pressure, heart rate and serum sodium concentration. There were no significant differences in heart rate, systolic and diastolic blood pressure between groups and over time until discharge. The fluid intake during the treatment period was significantly greater in the IV group (IV 1045±185 ml, OT 204±149 ml; p&lt;0.001). The average time to discharge for the OT group (58±23 min) was similar to that of the IV group (52.5±18 min; p=0.47). Conclusion Endurance athletes with EAPH can be treated effectively using the Trendelenburg position and oral fluids and the administration of intravenous fluids does not reduce the time to discharge. The findings of this study support the hypothesis that EAPH is a result of venous pooling due to peripheral vasodilatation, rather than dehydration.
Jean Mary Scott (née Lewis)
Authors: William Scott
Journal: BMJ (2005)

Former assistant paediatrician St Peter's Hospital, Chertsey (b Wolverhampton 1917; q Birmingham 1940; DCH), d 6 May 2005.​2005.




Figure 1




Jean was a captain in the Royal Army Medical Corps in 1943 and saw service in India and Malaysia as a medical specialist. She was demobilised in 1947. She started the blood transfusion service in Penang and then worked for the Singapore Anti-Tuberculosis Association before returning to England in 1962, where she was assistant paediatrician at St Peter's, Chertsey, and the White Lodge Centre. After retiring from the NHS she worked at the Charles Johnston Hospital, Nqutu, Zululand. Predeceased by her first husband, Angus, and her second husband, John, she leaves three sons; a stepson; and six grandchildren.
Synergistic Chemosensitivity of Triple-Negative Breast Cancer Cell Lines to Poly(ADP-Ribose) Polymerase Inhibition, Gemcitabine, and Cisplatin
Authors: Kedar Hastak, Elizabeth Alli, James M. Ford
Journal: Cancer Research (2010)

The basal-like subtype of breast cancer is characterized by a triple-negative (TN) phenotype (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2/neu negative). TN breast cancers share similar gene expression profiles and DNA repair deficiencies with BRCA1-associated breast cancers. BRCA1-mutant cells exhibit sensitivity to gemcitabine, cisplatin, and poly(ADP-ribose) polymerase (PARP) inhibition; therefore, we hypothesized that TN cancer cells may also exhibit sensitivity to these drugs. In this study, we report that TN breast cancer cells are more sensitive to these drugs compared with non-TN breast cancer cells. Moreover, combination treatments indicated that PARP inhibition by the small-molecule inhibitor PJ34 or siRNA knockdown synergized with gemcitabine and cisplatin in TN cells but not in luminal cancer cells. TN cells exhibited reduced repair of UV-induced cyclobutane pyrimidine dimers after PARP inhibition, suggesting that the synergistic effect of PJ34 and gemcitabine or cisplatin reflected inefficient nucleotide excision repair. Mechanistic investigations revealed that in TN cells, PJ34 reduced the levels of ΔNp63α with a concurrent increase in p73 and its downstream target p21. Thus, the sensitivity to combination treatment seemed to be mediated by sustained DNA damage and inefficient DNA repair triggering p63/p73-mediated apoptosis. Our results suggest a novel therapeutic strategy to treat women with TN breast cancer, an aggressive disease that presently lacks effective treatment options.
Delayed Cellular Maturation and Decreased Immunoglobulin κ Light Chain Production In Immature B Lymphocytes Lacking B Cell Linker Protein
Authors: Shengli Xu, Kong-Peng Lam
Journal: The Journal of Experimental Medicine (2002)

B cell linker (BLNK) protein is a component of the B cell receptor (BCR) signaling pathway and BLNK−/− mice have a block in B lymphopoiesis at the pro-B/pre-B cell stage. To study the effect of BLNK mutation at later stages of B cell development, we introduce an innocuous transgenic BCR into BLNK−/− mice and show that two populations of immature B cells distinguishable by their IgMlow (lo) and IgMhigh (hi) phenotypes are found in the bone marrow of these mice in contrast to a single population of IgMhi cells found in control BCR-transgenic BLNK+/+ mice. The mutant IgMlo and IgMhi cells are at an earlier developmental stage compared with the control IgMhi cells as indicated by their differential expression of CD43, B220, and major histocompatibility complex class II antigens and their timing of generation in culture. Thus, in the absence of BLNK the differentiation of immature B cells is delayed. Furthermore, mutant IgMlo cells produce equivalent level of immunoglobulin (Ig) μ but less Ig κ proteins than control and mutant IgMhi cells and this defect is attributed to a decrease in the amount of κ transcripts being generated. Finally, splenic B cells in BCR-transgenic BLNK−/− mice are predominantly of the transitional B cell phenotype and are rapidly lost from the peripheral B cell pool. Taken together, the data suggest a role for BLNK and perhaps BCR signaling, in the regulation of κ light chain expression and continued immature B cell differentiation.
Review: Varenicline increases risk for serious adverse cardiovascular events in tobacco users
Authors: James M Brophy
Journal: Annals of Internal Medicine (2011)

Source Citation Singh S, Loke YK, Spangler JG, Furberg CD. Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. CMAJ. 2011 Jul 4. [Epub ahead of print]. 21727225
High NPHP1 and NPHP6 Mutation Rate in Patients with Joubert Syndrome and Nephronophthisis
Authors: Ka[Combining Acute Accent]lma[Combining Acute Accent]n Tory, Tiphanie Lacoste, Lydie Burglen, Vincent Morinie[Combining Grave Accent]re, Nathalie Boddaert, Marie-Alice Macher, Brigitte Llanas, Hubert Nivet, Albert Bensman, Patrick Niaudet, Corinne Antignac, Re[Combining Acute Accent]mi Salomon, Sophie Saunier
Journal: Journal of the American Society of Nephrology (2007)

Joubert syndrome (JS) is an autosomal recessive disorder that is described in patients with cerebellar ataxia, mental retardation, hypotonia, and neonatal respiratory dysregulation. Kidney involvement (nephronophthisis or cystic renal dysplasia) is associated with JS in one fourth of known cases. Mutations in three genes--AHI1, NPHP1, and NPHP6--have been identified in patients with JS. However, because NPHP1 mutations usually cause isolated nephronophthisis, the factors that predispose to the development of neurologic involvement are poorly understood. In an attempt to identify such genetic determinants, a cohort of 28 families with nephronophthisis and at least one JS-related neurologic symptom were screened for mutations in AHI1, NPHP1, and NPHP6 genes. NPHP1 and NPHP6 homozygous or compound heterozygous mutations were found in 13 (46%) and six (21%) unrelated patients, respectively. Two of the 13 patients with NPHP1 mutations carried either a heterozygous truncating mutation in NPHP6 or a heterozygous missense mutation in AHI1. Furthermore, five patients with NPHP1 mutations carried the AHI1 variant R830W, which was predicted to be "possibly damaging" and was found with significantly higher frequency than in healthy control subjects and in patients with NPHP1 mutations without neurologic symptoms (five of 26 versus four of 276 and three of 152 alleles; P < 0.001 and P < 0.002, respectively). In contrast to the variable neurologic and milder retinal phenotype of patients with NPHP1 mutations, patients with NPHP6 mutations presented with a more severe neurologic and retinal phenotype. In conclusion, NPHP1 and NPHP6 are major genes of nephronophthisis associated with JS. Epistatic effects that are provided by heterozygous NPHP6 and AHI1 mutations and variants may contribute to the appearance of extrarenal symptoms in patients with NPHP1 mutations.
Is it reasonable to abandon obligatory vaccinations in Italy? A 2013 survey
Authors: C P Pelullo, S Marino, A J Valdes Abuadili, G Signoriello, F Attena
Journal: Eurosurveillance (2014)

In Italy, infant vaccinations are mandatory for four infectious diseases: diphtheria, polio, tetanus and hepatitis B. In the past, there was widespread apprehension in Italy that doing away with obligatory vaccinations would reduce the coverage rate, but the possibility of making vaccinations optional has recently become more popular. The objectives of this study were to investigate parental willingness to vaccinate their children if those vaccinations were no longer mandatory and to evaluate the variables influencing this intention. We conducted face-to-face structured interviews with 1,039 parents at public health vaccination centres in four cities of the Campania region of southern Italy. Most respondents (91.9%) said that they would certainly (69.4%) or probably (22.5%) vaccinate their children if vaccinations were not mandatory. The belief that vaccinations are effective and safe was positively associated with willingness to vaccinate their children, whereas having heard that autism is a possible adverse reaction to vaccination was inversely associated with willingness to vaccinate. Nevertheless, in the context of the relatively low 2012* [corrected] vaccination coverage rates in Campania (under the national standard of 95%), our results suggest that eliminating mandatory vaccinations is likely to lead to current coverage rates decreasing to unacceptably low levels, significantly below 90%.
PSF1, a DNA Replication Factor Expressed Widely in Stem and Progenitor Cells, Drives Tumorigenic and Metastatic Properties
Authors: Yumi Nagahama, Masaya Ueno, Satoru Miyamoto, Eiichi Morii, Takashi Minami, Naoki Mochizuki, Hideyuki Saya, Nobuyuki Takakura
Journal: Cancer Research (2010)

Abstract PSF1 (partner of sld five 1) is an evolutionarily conserved DNA replication factor implicated in DNA replication in lower species that is strongly expressed in a wide range of normal stem cell populations and progenitor cell populations. Because stem and progenitor cells possess high proliferative capacity, we hypothesized that PSF1 may play an important role in tumor growth. To begin to investigate PSF1 function in cancer cells, we cloned the mouse PSF1 promoter and generated lung and colon carcinoma cells that stably express a PSF1 promoter-reporter gene. Reporter expression in cells correlated with endogenous PSF1 mRNA expression. In a tumor cell xenograft model, high levels of reporter expression correlated with high proliferative activity, serial transplantation potential, and metastatic capability. Notably, cancer cells expressing reporter levels localized to perivascular regions in tumors and displayed expression signatures related to embryonic stem cells. RNAi-mediated silencing of endogenous PSF1 inhibited cancer cell growth by disrupting DNA synthesis and chromosomal segregation. These findings implicate PSF1 in tumorigenesis and offer initial evidence of its potential as a theranostic target. Cancer Res; 70(3); 1215–24
Anoikis and Survival Connections in the Tumor Microenvironment: Is There a Role in Prostate Cancer Metastasis?
Authors: Gabriela Rennebeck, Matthew Martelli, Natasha Kyprianou
Journal: Cancer Research (2005)

Abstract Overcoming the androgen independence of prostate tumors is considered the most critical therapeutic end point for improving survival in patients with metastatic prostate cancer. Normal epithelial and endothelial cells can undergo apoptosis when detached from the extracellular matrix (ECM), via the anoikis phenomenon. In contrast, tumor cells upon detachment from the ECM are capable of evading anoikis and metastasizing to different distant organs. Is the biological repertoire of the epithelial and endothelial cells sufficient to account for the events associated with the process of anoikis during prostate cancer metastasis? Although there is no clear answer to this question, what has become increasingly evident from the existing evidence is that molecules that induce anoikis in tumor epithelial and endothelial cells provide exciting new leads into effective therapeutic targeting as well as markers of prostate cancer progression and prediction of therapeutic resistance. This review analyzes recent findings on anoikis regulators and discusses the relevance of this unique apoptosis mode in the development of metastatic prostate cancer and identification of molecular signatures for treatment of advanced disease. (Cancer Res 2005; 65(24): 11230-5)