tbuckley/cabot-search huggingface dataset:
Abstract 346: Involvement of Non-canonical Wnt-PKC-JNK Pathway in Angiogenesis Enhanced by MSC Overexpressing Wnt11
Authors: Meifeng Xu, Jingcai Wang, Bin Yu
Journal: Circulation Research (2014)

Wnt11 is a key regulator of cardiac muscle cell proliferation and differentiation during heart development. Here, we hypothesized that preprogramming mesenchymal stem cells (MSC) with Wnt11 enhanced angiogenesis in ischemic myocardium. Methods and Results: An acute myocardial infarction model in SD rats was developed by ligation of the left anterior descending (LAD) coronary artery. Rat bone marrow derived MSC were transduced with Wnt11 gene (MSC-Wnt11) and transplanted into ischemic border area. The animals treated with MSC-Wnt11 showed a significantly improved cardiac function. Furthermore, fluorescent microsphere and histological studies revealed an increased blood flow and blood vessel density in MSC-Wnt11 transplanted animals. In vitro studies using conditioned medium (CdM) obtained from MSC-Wnt11 (CdM-Wnt11) showed an increased the length and number of capillary-like structure (CLS) formation and promoted migration of human umbilical vein endothelial cells (HUVECs), which was similar to that HUVECs were directly treated with recombinant Wnt11 proteins. However, these effects could be abolished by using a Wnt11 neutralizing antibody. Real-time PCR analysis indicated that the expression of novel PKCs including PKCδ, PKCε, PKCη, and PKCθ was significantly upregulated in HUVECs transduced with Wnt11 (H-Wnt11). Immunostaining and western blotting results showed that the protein levels of p-pan-PKC and p-JNK as well as VEGFA in H-Wnt11 were significantly higher than that in control HUVECs. However, no difference was detected in the expression of either p-p38 or p-ERK between H-Wnt11 and its control. Furthermore, the enhanced CLS formation and migration of HUVECs mediated by CdM-Wnt11 were partially abolished by using JNK inhibitor, SP600125 (5 μM) and PKC inhibitor, Calphostin-C (0.1 μM). Conclusion: Our results demonstrated, for the first time, that Wnt11 delivered by MSC improved cardiac function and promotes angiogenesis in ischemic myocardium, which may be associated with the activation of the non-canonical Wnt-PKC-JNK pathway.
Recombinant human erythropoietin for a Jehovah's witness with anemia of thermal injury
Authors: Lynn K. Boshkov, Edward E. Tredget, Anna Janowska‐Wieczorek
Journal: American Journal of Hematology (1991)

Abstract We report the use of recombinant human erythropoietin (rh‐Ep) as an alternative to transfusion therapy in a burn victim who was a Jehovah's Witness and refused blood transfusion. Despite endogenous elevated erythropoietin levels, the patient was reticulocytopenic and administration of rh‐Ep was accompanied by a 10‐fold increase in reticulocyte response and a rise in hemoglobin from 7.4 to 10.4 g/dl over a 12‐day period. We suggest that the exogenously administered erythropoietin overcame a clinically inadequate endogenous erythropoietin response.
The Diesel Exhaust in Miners Study: A Nested Case-Control Study of Lung Cancer and Diesel Exhaust
Authors: D. T. Silverman, C. M. Samanic, J. H. Lubin, A. E. Blair, P. A. Stewart, R. Vermeulen, J. B. Coble, N. Rothman, P. L. Schleiff, W. D. Travis, R. G. Ziegler, S. Wacholder, M. D. Attfield
Journal: JNCI Journal of the National Cancer Institute (2012)

Most studies of the association between diesel exhaust exposure and lung cancer suggest a modest, but consistent, increased risk. However, to our knowledge, no study to date has had quantitative data on historical diesel exposure coupled with adequate sample size to evaluate the exposure–response relationship between diesel exhaust and lung cancer. Our purpose was to evaluate the relationship between quantitative estimates of exposure to diesel exhaust and lung cancer mortality after adjustment for smoking and other potential confounders. We conducted a nested case–control study in a cohort of 12 315 workers in eight non-metal mining facilities, which included 198 lung cancer deaths and 562 incidence density–sampled control subjects. For each case subject, we selected up to four control subjects, individually matched on mining facility, sex, race/ethnicity, and birth year (within 5 years), from all workers who were alive before the day the case subject died. We estimated diesel exhaust exposure, represented by respirable elemental carbon (REC), by job and year, for each subject, based on an extensive retrospective exposure assessment at each mining facility. We conducted both categorical and continuous regression analyses adjusted for cigarette smoking and other potential confounding variables (eg, history of employment in high-risk occupations for lung cancer and a history of respiratory disease) to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Analyses were both unlagged and lagged to exclude recent exposure such as that occurring in the 15 years directly before the date of death (case subjects)/reference date (control subjects). All statistical tests were two-sided. We observed statistically significant increasing trends in lung cancer risk with increasing cumulative REC and average REC intensity. Cumulative REC, lagged 15 years, yielded a statistically significant positive gradient in lung cancer risk overall ( Ptrend = .001); among heavily exposed workers (ie, above the median of the top quartile [REC ≥ 1005 μg/m 3 -y]), risk was approximately three times greater (OR = 3.20, 95% CI = 1.33 to 7.69) than that among workers in the lowest quartile of exposure. Among never smokers, odd ratios were 1.0, 1.47 (95% CI = 0.29 to 7.50), and 7.30 (95% CI = 1.46 to 36.57) for workers with 15-year lagged cumulative REC tertiles of less than 8, 8 to less than 304, and 304 μg/m 3 -y or more, respectively. We also observed an interaction between smoking and 15-year lagged cumulative REC ( Pinteraction = .086) such that the effect of each of these exposures was attenuated in the presence of high levels of the other. Our findings provide further evidence that diesel exhaust exposure may cause lung cancer in humans and may represent a potential public health burden.
Mitral Systolic Murmurs
Authors: C. H. R. Carmichael
Journal: BMJ (1943)

We examined the effect of the antioxidant lazaroid U-74389F on acute lung injury induced in rabbits by phorbol myristate acetate (PMA). Thirty minutes after receiving either U-74389F (15 mg.kg-1 i.v.) or U-74389F vehicle, rabbits (n = 60) were given PMA (60 micrograms.kg-1 i.v.). PMA vehicle injected rabbits (n = 20) served as controls. Over a 5 h period after PMA or PMA vehicle injection, we measured arterial pH, arterial oxygen tension (Pa,O2), arterial carbon dioxide tension (Pa,CO2), and the plasma concentration of the neutrophil chemoattractant interleukin-8 (IL-8). At postmortem, lungs were inspected for macroscopic injury and examined histologically. Malondialdehyde levels were assayed in lung tissue as an index of lipid peroxidation. In bronchoalveolar lavage (BAL), total and differential cell counts, protein and IL-8 concentrations were measured. Compared to normal controls, rabbits challenged with PMA alone developed arterial acidosis, hypercapnia and hypoxaemia, accompanied by significant rise in plasma IL-8 concentration. U-74389F pretreated animals did not develop significant arterial blood gas abnormalities and had significantly lower IL-8 concentration in plasma. U-74389F did not prevent PMA-induced lipid peroxidation. However, macroscopic signs of lung injury and the degree of alveolar haemorrhage and protein extravasation were significantly less severe in pretreated rabbits than in those given PMA alone. In addition, U-74389F significantly reduced IL-8 concentration and neutrophil number in BAL. By histological assessment, 80% of lung neutrophils were localized in alveolar spaces of animals receiving PMA alone. Conversely, in U-74389F pretreated animals, 75% of neutrophils were distributed within extra-alveolar blood vessels and alveolar septa. We conclude that lazaroid U-74389F attenuates lung injury in rabbits given PMA by preventing neutrophil migration into pulmonary alveoli. This effect may, in part, be related to downregulation of IL-8 production.
Breast Cancer Mortality After a Diagnosis of Ductal Carcinoma In Situ
Authors: Steven A. Narod, Javaid Iqbal, Vasily Giannakeas, Victoria Sopik, Ping Sun
Journal: JAMA Oncology (2015)

Women with ductal carcinoma in situ (DCIS), or stage 0 breast cancer, often experience a second primary breast cancer (DCIS or invasive), and some ultimately die of breast cancer.To estimate the 10- and 20-year mortality from breast cancer following a diagnosis of DCIS and to establish whether the mortality rate is influenced by age at diagnosis, ethnicity, and initial treatment received.Observational study of women who received a diagnosis of DCIS from 1988 to 2011 in the Surveillance, Epidemiology, and End Results (SEER) 18 registries database. Age at diagnosis, race/ethnicity, pathologic features, date of second primary breast cancer, cause of death, and survival were abstracted for 108,196 women. Their risk of dying of breast cancer was compared with that of women in the general population. Cox proportional hazards analysis was performed to estimate the hazard ratio (HR) for death from DCIS by age at diagnosis, clinical features, ethnicity, and treatment.Ten- and 20-year breast cancer-specific mortality.Among the 108 196 women with DCIS, the mean (range) age at diagnosis of DCIS was 53.8 (15-69) years and the mean (range) duration of follow-up was 7.5 (0-23.9) years. At 20 years, the breast cancer-specific mortality was 3.3% (95% CI, 3.0%-3.6%) overall and was higher for women who received a diagnosis before age 35 years compared with older women (7.8% vs 3.2%; HR, 2.58 [95% CI, 1.85-3.60]; P < .001) and for blacks compared with non-Hispanic whites (7.0% vs 3.0%; HR, 2.55 [95% CI, 2.17-3.01]; P < .001). The risk of dying of breast cancer increased after experience of an ipsilateral invasive breast cancer (HR, 18.1 [95% CI, 14.0-23.6]; P < .001). A total of 517 patients died of breast cancer following a DCIS diagnosis (mean follow-up, 7.5 [range, 0-23.9] years) without experiencing an in-breast invasive cancer prior to death. Among patients who received lumpectomy, radiotherapy was associated with a reduction in the risk of ipsilateral invasive recurrence at 10 years (2.5% vs 4.9%; adjusted HR, 0.47 [95% CI, 0.42-0.53]; P < .001) but not of breast cancer-specific mortality at 10 years (0.8% vs 0.9%; HR, 0.86 [95% CI, 0.67-1.10]; P = .22).Important risk factors for death from breast cancer following a DCIS diagnosis include age at diagnosis and black ethnicity. The risk of death increases after a diagnosis of an ipsilateral second primary invasive breast cancer, but prevention of these recurrences by radiotherapy does not diminish breast cancer mortality at 10 years.
Clinical practice guidelines
Authors: S V Jassal, J M Roscoe, J S Zaltzman, T Mazzulli, M Krajden, M Gadawski, D C Cattran, C J Cardella, S E Albert, E H Cole
Journal: Journal of the American Society of Nephrology (1998)

OBJECTIVE To develop a set of comprehensive, standardized, evidence-based guidelines for the use of antiviral therapy to prevent cytomegalovirus disease in adult patients having undergone renal transplantation. OPTIONS The use of medication, at the time of induction therapy or at the earliest sign of viremia. Treatments were evaluated by patient and donor serologic groups and the induction regimen used. OUTCOMES The control of symptoms and features of cytomegalovirus disease over the first 6 mo to 1 yr after transplantation. EVIDENCE Articles, compiled using a MEDLINE search from 1976 to July 1997, were reviewed by representatives of nephrology, microbiology, pharmacy, and epidemiology. Additional information was obtained from recent review articles and conference abstracts, and from experts in the field. VALUES The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examinations were used. High value was placed on studies with a randomized controlled design and blinded outcome observers. Study quality was classified as poor when cointervention was present (especially with regard to immunosuppressive regimens), when more than 20% of patients were lost to follow-up, and when intention to treat analysis was not performed. Recommendations were made with a graded system (grades A and B: Use of the intervention advised, based on high or fair quality evidence, respectively; grades D and E: Use of the intervention not advised, based on high or fair quality evidence, respectively: grade C: No recommendation made because of insufficient or conflicting evidence). RECOMMENDATIONS (1) Seropositive recipient; donor seropositive or seronegative; immunosuppression with antilymphocyte products. Prophylaxis with antiviral therapy recommended (grade A recommendation). (2) Seronegative recipient; seropositive donor; immunosuppression with antilymphocyte products. Prophylaxis with antiviral therapy recommended (grade A recommendation) (3) Seronegative recipient; seropositive donor; conventional immunosuppression. Prophylaxis with antiviral therapy recommended (grade B recommendation). (4) Seronegative recipient; seronegative donor; any immunosuppressive regimen. No prophylaxis with antiviral therapy required (grade D/E recommendation). (5) Seropositive recipient: donor seropositive or seronegative; conventional immunosuppression. Prophylaxis left to the discrimination of the physician in charge (grade C recommendation).
Synonymous codon usage variation among Giardia lamblia genes and isolates
Authors: B. Lafay, P. M. Sharp
Journal: Molecular Biology and Evolution (1999)

The pattern of codon usage in the amitochondriate diplomonad Giardia lamblia has been investigated. Very extensive heterogeneity was evident among a sample of 65 genes. A discrete group of genes featured unusual codon usage due to the amino acid composition of their products: these variant surface proteins (VSPs) are unusually rich in Cys and, to a lesser extent, Gly and Thr. Among the remaining 50 genes, correspondence analysis revealed a single major source of variation in synonymous codon usage. This trend was related to the extent of use of a particular subset of 21 codons which are inferred to be those which are optimal for translation; at one end of this trend were genes expected to be expressed at low levels with near random codon usage, while at the other extreme were genes expressed at high levels in which these optimal codons are used almost exclusively. These optimal codons all end in C or G so G + C content at silent sites varies enormously among genes, from values around 40%, expected to reflect the background level of the genome, up to nearly 100%. Although VSP genes are occasionally extremely highly expressed, they do not, in general, have high frequencies of optimal codons, presumably because their high expression is only intermittent. These results indicate that natural selection has been very effective in shaping codon usage in G. lamblia. These analyses focused on sequences from strains placed within G. lamblia "assemblage A"; a few sequences from other strains revealed extensive divergence at silent sites, including some divergence in the pattern of codon usage.
Reflections on Medical Oncology: 25 Years of Clinical Trials—Where Have We Come and Where Are We Going?
Authors: Christopher M. Booth, Ian Tannock
Journal: Journal of Clinical Oncology (2007)

Twenty-five years ago in the first issue of Journal of Clinical Oncology, Tannock and Murphy 1 appealed for better design and improved reporting of clinical trials in oncology, and proposed five areas in which journals and investigators could improve the quality of clinical cancer research.As shown in Figure 1, these recommendations pertain to three inter-related themes: appropriate design and size of trials, the selection of clinically relevant end points, and reporting that is free of bias.In this Silver Anniversary issue, we reflect on how well the evolution of clinical trials has adhered to these principles during the last 25 years.
A New Element in the Mechanism of Asthma
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (2002)

Type 2 helper T (Th2) cells, a type of CD4 T cell, trigger allergic inflammation and the production of antibodies. Type 1 helper T (Th1) cells produce interferon-γ, which suppresses Th2 cells. Th2 cells have a prominent role in asthma. T-bet, a transcription factor required for the production of interferon-γ, was found in a recent study to be lacking in lymphocytes from the bronchi of patients with asthma, and asthma developed in mice with experimentally disabled T-bet genes.
The complete mitochondrial DNA sequence of the greater Indian rhinoceros, Rhinoceros unicornis, and the Phylogenetic relationship among Carnivora, Perissodactyla, and Artiodactyla (+ Cetacea)
Authors: X. Xu, A. Janke, U. Arnason
Journal: Molecular Biology and Evolution (1996)

The sequence (16,829 nt) of the complete mitochondrial genome of the greater Indian rhinoceros, Rhinoceros unicornis, was determined. Like other perissodactyls studied (horse and donkey) the rhinoceros demonstrates length variation (heteroplasmy) associated with different numbers of repetitive motifs in the control region. The 16,829-nt variety of the molecule includes 36 identical control region motifs. The evolution of individual peptide-coding genes was examined by comparison with a distantly related perissodactyl, the horse, and the relationships among the orders Carnivora, Perissodactyla, and Artiodactyla (+ Cetacea) were examined on the basis of concatenated sequences of 12 mitochondrial peptide-coding genes. The phylogenetic analyses grouped Carnivora, Perissodactyla, and Artiodactyla (+ Cetacea) into a superordinal clade and within this clade a sister group relationship was recognized between Carnivora and Perissodactyla to the exclusion of Artiodactyla (+ Cetacea) . On the basis of the molecular difference between the rhinoceros and the horse and by applying as a reference to Artiodactyl/Cetacean divergence set at 60 million years ago (MYA), the evolutionary divergence between the families Rhinocerotidae and Equidae was dated to approximately 50 MYA.
Prevalence of severe congenital heart disease after folic acid fortification of grain products: time trend analysis in Quebec, Canada
Authors: R. Ionescu-Ittu, A. J Marelli, A. S Mackie, L. Pilote
Journal: BMJ (2009)

<b>Objective</b> To investigate whether the 1998 government policy for mandatory fortification of flour and pasta products with folate was followed by a reduction in the prevalence of severe congenital heart defects. <b>Design</b> Time trend analysis. <b>Setting</b> Province of Quebec, Canada. <b>Participants</b> Infants born in 1990-2005 identified with severe congenital heart defects (tetralogy of Fallot, endocardial cushion defects, univentricular hearts, truncus arteriosus, or transposition complexes) in Quebec administrative databases. <b>Methods</b> Data analysed in two time periods (before and after fortification). Birth prevalence measured annually as infants (live and stillbirths) with severe congenital heart defects per 1000 births in Quebec. Changes in the birth prevalence from the period before to the period after fortification were estimated with Poisson regression. <b>Results</b> Among the 1 324 440 births in Quebec in 1990-2005 there were 2083 infants born with severe congenital heart defects, corresponding to an average birth prevalence of 1.57/1000 births. Time trend analysis showed no change in the birth prevalence of severe birth defects in the nine years before fortification (rate ratio 1.01, 95% confidence interval 0.99 to 1.03), while in the seven years after fortification there was a significant 6% decrease per year (0.94, 0.90 to 0.97). <b>Conclusions</b> Public health measures to increase folic acid intake were followed by a decrease in the birth prevalence of severe congenital heart defects. These findings support the hypothesis that folic acid has a preventive effect on heart defects.
Reply to G. Gandaglia et al
Authors: Chunkit Fung, Sophie D. Fossa, Michael T. Milano, Jan Oldenburg, Lois B. Travis
Journal: Journal of Clinical Oncology (2014)

Fung et al 1 compared the risks of secondary malignancies among patients treated with chemotherapy or surgery alone for testicular nonseminoma.Utilizing the population-based SEER cohort, Fung et al found that chemotherapy-treated men had a 40% increased risk of developing secondary malignancies after initial diagnosis.Although the study is without doubt an important assessment given the rising incidence of testicular cancer in the last decades, several limitations should be raised, which may weaken the clinical applicability of their findings in the contemporary era.First, since the study span covered diagnoses from 1980 to 2008, Fung et al 1 could not account for the variable chemotherapy regimens that were introduced over time. [2]3][4][5] Patients diagnosed and treated in more recent years with newer and less toxic chemotherapy regimens might be at considerably lower risk of secondary malignancies compared to historical chemotherapy regimens used 30 years ago.Second, the lack of consideration for disease stage in the calculation of standardized incidence ratios for secondary malignancies further augments the heterogeneity of the studied population.Of note, 34% of patients treated with chemotherapy harbored metastatic disease versus 1.7% in the surgery group.Given the prevalence of metastatic patients in the chemotherapy group, Fung et al are unable to rule out the confounding effect of biologic mechanisms.Specifically, inheritance of both rare genetic variants and polygenic trait predisposing to the development of advanced disease, may ultimately increase the risks of a new onset of secondary malignancies. 6,7 Third, the number of cycles and dosage received is equally unknown.For example, metastatic patients are likely to be exposed to significantly higher cumulative doses of chemotherapeutic agents compared to individuals with stage I testicular nonseminoma. 8Thus, the current study is not able to provide insight into the dose-response relationship between chemotherapy and the subsequent risk of solid malignancies.In conclusion, the evaluation of the potential role of chemotherapy on the development of secondary malignancies relative to surgery in patients with testicular nonseminoma is highly relevant.However several other important aspects-improvements in chemotherapy regimens used in contemporary years, a better defined population according to disease stage, better knowledge of dosage and cycles used-need to be factored in the assessment of this association to avoid over-attributing the long-term adverse effects of chemotherapy.