tbuckley/cabot-search huggingface dataset:
Mitochondrial DNA sequence variation in the spruce budworm species complex (Choristoneura: Lepidoptera).
Authors: F A Sperling, D A Hickey
Journal: Molecular Biology and Evolution (1994)

A combination of polymerase-chain-reaction amplification and automated DNA sequencing was used to survey variation in a species complex of pest insects, the spruce budworms (Choristoneura fumiferana species group), and an outgroup species, C. rosaceana. We sequenced an mtDNA region of 1,573 bp that extends from the middle of cytochrome oxidase subunit I (COI) through tRNA leucine (UUR) to the end of cytochrome oxidase subunit II. In addition, we examined levels of intraspecific variation within a 470-bp region of the COI gene. Choristoneura fumiferana clearly represented the oldest lineage within its species group, with 2.7%-2.9% sequence divergence from the other species. In contrast, the four remaining species (C. pinus, C. biennis, C. occidentalis, and C. orae) had closely related or identical mtDNA, with < 1% divergence among most of their haplotypes. Despite its older lineage and widespread geographic distribution, C. fumiferana showed significantly lower intraspecific genetic diversity than did C. occidentalis. Choristoneura orae shared haplotypes with C. occidentalis and C. biennis, and species-level separation of these three species was not supported. Two divergent, uncommon haplotypes were also found in C. occidentalis and C. biennis. The divergent haplotype in C. biennis had an unusually high number of inferred amino acid replacements, suggesting selective differences between mitochondrial DNA haplotypes. Transition:transversion ratios in Choristoneura paralleled those found in Drosophila; transition:transversion ratios were highest in closely related sequences but decreased with increasing sequence divergence. Nucleotide composition showed an A+T bias that was near the high end of the range known for insects. This work illustrates the potential utility of direct DNA sequencing in assessing population structures, species limits, and phylogenetic relationships among organisms that have not previously been subjected to DNA analysis.
Bioavailability of low-dose oral etoposide.
Authors: K R Hande, M G Krozely, F A Greco, J D Hainsworth, D H Johnson
Journal: Journal of Clinical Oncology (1993)

PURPOSE To determine the bioavailability of oral etoposide capsules administered at doses of 100 mg and 400 mg. PATIENTS AND METHODS The bioavailability of oral etoposide was determined by measuring the area under the etoposide plasma concentration versus time curve (AUC) following intravenous (IV) etoposide administration and comparing that value to the AUC achieved following an oral dose administered 1 day later to the same patient. The bioavailability of a 100-mg oral dose of etoposide was measured on 16 occasions in 11 patients. The bioavailability of a 400-mg dose was determined on 12 occasions in six patients. RESULTS The mean (+/- SD) bioavailability following a 100-mg dose of oral etoposide was 76% +/- 22%, which was significantly greater (P &lt; .01) than the mean bioavailability of 48% +/- 18% following a 400-mg oral dose. The coefficient of variation in oral etoposide bioavailability was significant: 29% with a 100-mg oral dose and 37% with a 400-mg dose. CONCLUSION Bioavailability of a 100-mg oral etoposide dose is greater than suggested in the package insert from Bristol Laboratories (Evansville, IN). Comparable oral etoposide doses are not uniformly twice that of an IV dose, as suggested by the package insert, but will depend on the final oral dose administered. Bioavailability is better at lower oral etoposide doses. This study confirms the wide interpatient and intrapatient variability in oral etoposide bioavailability.
Abstract A27: Transposon mutagenesis screen identifies genes conferring resistance to BRAF inhibition in melanoma
Authors: Li Chen, Anahita Dastur, Xunqin Yin, Cyril Benes
Journal: Clinical Cancer Research (2015)

Abstract Drug resistance states can be affected by altered gene expression levels or functions. We sought to systematically identify genes that could confer resistance to BRAF inhibition in BRAF mutant melanoma by applying a novel transposon mutagenesis screening approach. Resistant genes identified in this study include both well-characterized molecules such as BRAF, CRAF, PTEN and many other genes whose functions have not been previously associated with drug resistance, and encompass functional groups such as signaling pathway components, transcription factors, ubiquitination and sumoylation enzymes, and G-protein coupled receptors. Overexpression of these genes also confers resistance to the MEK inhibitor AZD6244 demonstrating a pathway specific activity. The resistance mechanisms are diverse: some demonstrate elevated ERK or PI3K signaling, while others do not appear to be signaling-related. Two genes identified in this study elicit both ERK and AKT signals and respectively increase the EGFR baseline expression and PLX4720-induced phosphorylation. Combined treatment with EGFR and BRAF inhibitors in these two clones demonstrated marked drug synergy. Taken together with recently published studies implicating EGFR in resistance to BRAF our study indicates that multiple mechanisms of resistance to BRAF inhibitors can converge on EGFR signaling. Our study identifies additional genes that could be used to select patients most likely to benefit from treatments combining EGFR inhibitors with BRAF/MEK inhibitors to overcome resistance. Citation Format: Li Chen, Anahita Dastur, Xunqin Yin, Cyril Benes. Transposon mutagenesis screen identifies genes conferring resistance to BRAF inhibition in melanoma. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A27.
Phosphoinositide 3-Kinase-C2α Regulates Polycystin-2 Ciliary Entry and Protects against Kidney Cyst Formation
Authors: Irene Franco, Jean Piero Margaria, Maria Chiara De Santis, Andrea Ranghino, Daniel Monteyne, Marco Chiaravalli, Monika Pema, Carlo Cosimo Campa, Edoardo Ratto, Federico Gulluni, David Perez-Morga, Stefan Somlo, Giorgio R Merlo, Alessandra Boletta, Emilio Hirsch
Journal: Journal of the American Society of Nephrology (2015)

Signaling from the primary cilium regulates kidney tubule development and cyst formation. However, the mechanism controlling targeting of ciliary components necessary for cilium morphogenesis and signaling is largely unknown. Here, we studied the function of class II phosphoinositide 3-kinase-C2α (PI3K-C2α) in renal tubule-derived inner medullary collecting duct 3 cells and show that PI3K-C2α resides at the recycling endosome compartment in proximity to the primary cilium base. In this subcellular location, PI3K-C2α controlled the activation of Rab8, a key mediator of cargo protein targeting to the primary cilium. Consistently, partial reduction of PI3K-C2α was sufficient to impair elongation of the cilium and the ciliary transport of polycystin-2, as well as to alter proliferation signals linked to polycystin activity. In agreement, heterozygous deletion of PI3K-C2α in mice induced cilium elongation defects in kidney tubules and predisposed animals to cyst development, either in genetic models of polycystin-1/2 reduction or in response to ischemia/reperfusion-induced renal damage. These results indicate that PI3K-C2α is required for the transport of ciliary components such as polycystin-2, and partial loss of this enzyme is sufficient to exacerbate the pathogenesis of cystic kidney disease.
Organ Donation After Circulatory Death—Reply
Authors: Stephen P. Wall, Carolyn Plunkett, Arthur Caplan
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Adjuvant treatment of stage I lung cancer with high-dose vitamin A.
Authors: U Pastorino, M Infante, M Maioli, G Chiesa, M Buyse, P Firket, N Rosmentz, M Clerici, E Soresi, M Valente
Journal: Journal of Clinical Oncology (1993)

Vitamin A and retinoids are strong inhibitors of epithelial cancer promotion and progression in experimental carcinogenesis. This study examined whether they may prevent the occurrence of upper aerodigestive cancer in subjects heavily exposed to tobacco smoking, such as patients already cured of an early-stage lung cancer.The adjuvant effect of high-dose vitamin A was tested on 307 patients with stage I non-small-cell lung cancer. After curative surgery, patients were randomly assigned to either a group prescribed retinol palmitate administration (orally 300,000 IU daily for 12 months) or a control group prescribed no treatment.After a median follow-up of 46 months, the number of patients with either recurrence or new primary tumors was 56 (37%) in the treated arm and 75 (48%) in the control arm. Eighteen patients in the treated group developed a second primary tumor, and 29 patients in the control group developed 33 second primary tumors. A statistically significant difference in favor of treatment was observed concerning time to new primary tumors in the field of prevention (P = .045, log-rank test). The treatment difference in terms of disease-free interval was close to statistical significance (P = .054, log-rank test) and just significant when adjusted for primary tumor classification (P = .038, Cox regression model).Daily oral administration of high-dose vitamin A is effective in reducing the number of new primary tumors related to tobacco consumption and may improve the disease-free interval in patients curatively resected for stage I lung cancer. The impact of such a treatment on survival needs to be further explored.
Illusion and reality: practical pitfalls in interpreting clinical trials.
Authors: E Glatstein, R W Makuch
Journal: Journal of Clinical Oncology (1984)

This paper has attempted to review for the reader some of the common problem areas in the interpretation of results of cancer treatment. The intention has been to point out potential pitfalls in interpretation so that the reader can comprehend the literature with more insight and criticalness . The plethora of journals and ongoing investigations indicates a greater need for critical understanding on the part of readers. This understanding stretches from the definitions of success and failure used in generating survival curves, to the accumulation and analysis of data and presentation of the results. We hope this paper will help the reader to achieve a greater degree of that understanding.
Laboratory investigation of sputum and mucociliary clearance (MCC) condition in patients with COPD
Authors: Tetyana Pertseva, Olena Lykholat, Olena Gurzhiy
Journal: European Respiratory Journal (2011)

Aim: To investigate biochemical parameters of sputum for evaluation of MCC's disorders in patients with COPD.

Materials: 90 smoking patients with COPD in stable condition.

Methods: Biochemical parameters of sputum (medium weight molecules (MWM), trypsin, cysteine proteases cathepsin B, cathepsin L, α1-proteinase inhibitor (α1-PI)) were researched for MCC's evaluation.

Results: Dynamics of indices are in table 1.

View this table:

Table 1





Conclusions: Bronchial obstruction progression accompanied by decreasing of local proteolytic potential of sputum: trypsin (r= -0,61, p<0,001); cathepsin B (r= -0,42, p<0,01); cathepsin L (r=0,39, p<0,01); α1-PI (r=0,39, p<0,01). It leads to decreasing of sputum lysis and accumulation of hyperviscosity mucus in respiratory tract. As a result, movement of ciliary epithelium is blocked.

Decreasing of sputum lytic properties accompanied by accumulation of MWM (correlation between severity of COPD and MWM level – r=0,60, p<0,001). It also enhances the viscosity of sputum and violates the optimal conditions of MCC functioning.

So, bronchial obstruction progression in patients with COPD accompanied by decreasing of common lytic activity of sputum, therefore excessive amount of viscous bronchial secretion accumulate. It slows down ciliary epithelium movement, compounding the disorders of MCC.
Phase I study of recombinant human interleukin-3 in patients with bone marrow failure.
Authors: R Kurzrock, M Talpaz, Z Estrov, M G Rosenblum, J U Gutterman
Journal: Journal of Clinical Oncology (1991)

Interleukin-3 (IL-3) is a T-cell-derived colony-stimulating factor (CSF) whose primary targets include relatively early, multipotential, hematopoietic progenitor cells. In this trial, we treated 24 patients with recombinant human IL-3 given by a daily 4-hour intravenous infusion for 28 days. The dose levels were 30, 60, 125, 250, 500, 750, and 1,000 micrograms/m2/d. At least three patients were entered at every dose level. Each participant suffered from bone marrow failure, with the underlying diagnosis being myelodysplastic syndrome (13 patients), aplastic anemia (eight patients), or aplasia after prolonged high-dose chemotherapy (three patients) for multiple myeloma, breast cancer, or acute myelogenous leukemia. Most patients tolerated therapy well, with the most frequent side effects being low-grade fever and headaches. Hematopoietic changes included modest increases in neutrophil counts (eight patients), eosinophil counts (six patients), platelet counts (three patients), and reticulocyte counts (two patients). An increase in blasts occurred in one patient who had refractory anemia with excess blasts in transformation and was reversible once IL-3 was discontinued. In addition, one patient with chronic myelomonocytic leukemia showed an increase in monocytes (and granulocytes). Progression to acute leukemia did not occur. Pharmacokinetic analyses showed a rapid clearance with a mean half-life of 18.8 minutes at the 60 micrograms/m2/d dose, and 52.9 minutes at the 250 micrograms/m2/d dose. Serum concentrations of 10 to 20 ng/mL of IL-3 were achievable at the 250 micrograms/m2/d dose. Our observations indicate that recombinant human IL-3 can be given safely at doses of 1,000 micrograms/m2/d or less. In addition, on the basis of preclinical data and the biologic activity observed in this study, further trials of this molecule, alone and in combination with other growth factors, are warranted in patients with pancytopenia.
Quality-of-Life Measures in Children and Adults With Type 1 Diabetes
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate the impact of continuous glucose monitoring (CGM) on quality of life (QOL) among individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS In a multicenter trial, 451 children and adults with type 1 diabetes were randomly assigned to CGM treatment or the control group. Generic and diabetes-specific QOL questionnaires were completed at baseline and 26 weeks by all participants and parents of participants &amp;lt;18 years old, and the CGM satisfaction scale was completed by the CGM group (participants and parents) at 26 weeks. RESULTS After 26 weeks, QOL scores remained largely unchanged for both the treatment and the control group, although there was a slight difference favoring the adult CGM group on several subscales (P &amp;lt; 0.05). There was substantial satisfaction with CGM technology after 26 weeks among participants and parents. CONCLUSIONS Baseline QOL was high, and the measures showed little change with CGM use, although a high level of CGM satisfaction was reported.
Role of mitochondrial biogenesis in asthmatic airway smooth muscle proliferation: Forever young
Authors: Valerie Siao, Thomas Trian, Patrick Berger, Michael Fayon
Journal: European Respiratory Journal (2014)

Increased bronchial smooth muscle mass is one of the key structural features of severe asthma. In adults, asthmatic airway smooth muscle cells (ASMC) demonstrate greater mitochondrial biogenesis associated with an increase in ASMC proliferation rate vs non-asthmatic ASMC. There is no evidence that such a difference between asthmatic and non-asthmatic ASMC occurs in pre-school children.

The primary aim of the study was to compare asthmatic and non-asthmatic ASMC proliferation and mitochondrial biogenesis in adults and pre-school children. The secondary aim was to assess the effect of factors released by the epithelium upon stimulation by environmental factors (rhinovirus RV, house dust mite HDM) on ASMC proliferation.

We cultured ASMC and bronchial epithelial cells(BEC) obtained by endobronchial biopsy from children and adults with severe asthma or no. We studied ASMC proliferation (cell counting and CFSE dye assay) in 10% fetal bovine serum and after the addition of the BEC culture supernatant obtained after RV infection, HDM exposure or both. Mitochondrial mass and biogenesis were determined by western blot.

ASMC proliferation and mitochondrial mass were increased in asthmatic adults, asthmatic and control children ASMC vs control adults, with a cell doubling time of 35.0±2.5 h, 24.8±1.9h, 22.6±2.6h vs 47.4±4.4h (p<0.05) and a porine rate at 50%, 53%, 52% vs 20%. RV and HDM exposure induced an increase of 120,5% and 107.7% compared to the basal proliferation rate in asthmatic subjects only.

As previously described in adult asthmatics, ASMC proliferation is enhanced in both asthmatic and non-asthmatic children. This is associated with an increase in mitochondrial mass and biogenesis.
An Official American Thoracic Society/American College of Chest Physicians Policy Statement: Implementation of Low-Dose Computed Tomography Lung Cancer Screening Programs in Clinical Practice
Authors: Renda Soylemez Wiener, Michael K. Gould, Douglas A. Arenberg, David H. Au, Kathleen Fennig, Carla R. Lamb, Peter J. Mazzone, David E. Midthun, Maryann Napoli, David E. Ost, Charles A. Powell, M. Patricia Rivera, Christopher G. Slatore, Nichole T. Tanner, Anil Vachani, Juan P. Wisnivesky, Sue H. Yoon
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Section:ChooseTop of pageAbstract <<ContentsOverviewIntroductionMethodsResultsPlanningImplementationMaintenanceConclusionsReferencesCITING ARTICLES
Airway Endothelial Dysfunction in Asthma and Chronic Obstructive Pulmonary Disease
Authors: Adam Wanner, Eliana S. Mendes
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Endothelial dysfunction in the extrapulmonary circulation has been linked to cardiovascular disease. Recent investigations have revealed that in the airway circulation, cigarette smoking, chronic obstructive pulmonary disease (COPD), and asthma are also accompanied by endothelial dysfunction. Inhaled glucocorticosteroids can partially or fully restore normal endothelium-dependent vasodilation in these conditions, thereby identifying the airway endothelium as a novel therapeutic target in the treatment of airway disease. The role of the defective endothelium-dependent vasodilation in the pathophysiology in asthma and COPD is still subject to speculation. However, there appears to be an association between COPD and extrapulmonary vascular dysfunction, and the possibility exists that the use of inhaled glucocorticosteroids has a beneficial effect on cardiovascular disease in COPD as suggested by database studies showing that inhaled glucocorticosteroids reduce the incidence of nonfatal and fatal cardiovascular events in COPD.
Do atopy predict severity of asthma
Authors: Rajesh Yadavilli, Kimberly Su, Rachel Penfold, Jennifer Whiteley, Sidrah Mohammad, Mithun Murthy, Hassan Burhan
Journal: European Respiratory Journal (2013)

Introduction: 

Atopy is the tendency to develop an immunoglobulin E antibody response to common allergens. Even though atopy is strongly considered as predisposing factor of asthma, not all asthma is allergic in nature. The relationship between atopy and asthma severity is complex and not well established.

Hypothesis: 

Patients with atopy have severe asthma and poor control compared to non-atopics.

Methods: 

108 patients with asthma diagnosed in specialist asthma clinic were randomly studied retrospectively for asthma severity and control. Non-Asthma cases were excluded using either history, lung function tests or normal bronchial challenge test. Patients with total IgE >100 IU/ml were considered atopic. Statistical analysis was performed using Unpaired t-test or Mann-Whitney U test for continuous variables.

Results: 

Mean age of 62 Non-atopic patients was 51.06 yrs and 46 Atopic patients was 46.91 yrs.

Atopic patients were on higher treatment for asthma with mean British thoracic society (BTS) step of 3.89 compared to non-atopic patients, BTS step of 3.45; P=0.024.

39% of Atopics were taking oral steroids compared to 16% of non- atopics; P=0.03.

There is no statistical significance between the two groups in Forced expiratory volume in 1 second(Fev1), P=0.55; Fev1%, P=0.6; Asthma control test (ACT), P=0.33; Asthma quality of life questionnaire(AQLQ), P=0.17; Hospital Asthma Admissions/ yr, P=0.70; Mean inhaled steroid dose in 24hrs, P=0.58 and Usage of inhaled steroid and long acting beta agonist combination inhalers, P=0.71.

Conclusions: 

Even though there is no significant association between Atopy and severity or control of asthma, These patients are younger and were using more oral steroids there by scoring high on BTS step for asthma severity.
Genotoxic Effects of Sunlight-Activated Waste Water in Cultured Mammalian Cells&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Gary F. Strniste, David J. Chen, Richard T. Okinaka
Journal: JNCI Journal of the National Cancer Institute (1982)

Cultured Chinese hamster ovary cells were incubated with dilutions of an oil shale retort process water and exposed to nautral sunlight. An enhancement of sevenfold to ninefold was seen in photoinduced cytotoxicity (by a colony-forming assay) and mutagenicity [at the hypoxanthine phosphoribosyltransferase (HPRT) locus] for cells pretreated with the process water compared to effects seen in cells exposed to sunlight only. Significant photoinduced cytotoxicity was also observed in cultured human skin fibroblasts when exposed to the process water before being exposed to near UV (NUV) radiation. The mutation frequencies (determined for the HPRT locus) induced by the process water and NUV radiation were as great as those frequencies seen for far UV light alone. Increases in genotoxicity were observed in excision repair-deficient xeroderma pigmentosum skin fibroblasts when compared to the responses seen in normal cells. Risks to health resulting from the phototransformation of these oil shale retort process waste waters are unassessed at this time.