tbuckley/cabot-search huggingface dataset:
"Silent" sites in Drosophila genes are not neutral: evidence of selection among synonymous codons.
Authors: D C Shields, P M Sharp, D G Higgins, F Wright
Journal: Molecular Biology and Evolution (1988)

The patterns of synonymous codon usage in 91 Drosophila melanogaster genes have been examined. Codon usage varies strikingly among genes. This variation is associated with differences in G+C content at silent sites, but (unlike the situation in mammalian genes) these differences are not correlated with variation in intron base composition and so are not easily explicable in terms of mutational biases. Instead, those genes with high G+C content at silent sites, resulting from a strong "preference" for a particular subset of the codons that are mostly C-ending, appear to be the more highly expressed genes. This suggests that G+C content is reduced in sequences where selective constraints are weaker, as indeed seen in a pseudogene. These and other data discussed are consistent with the effects of translational selection among synonymous codons, as seen in unicellular organisms. The existence of selective constraints on silent substitutions, which may vary in strength among genes, has implications for the use of silent molecular clocks.
How can identified early presence of atherosclerotic plaque in severe OSAS
Authors: Roberto Bossi, Claudio Carnevale, Roberto Meazza
Journal: European Respiratory Journal (2011)

Carotid plaque is frequent and often unacknowledged in severe OSAS. Ultrasonographic evaluation of the carotid arteries is the fastest way to disclose a different level of stenosis in absence of clinical symptoms, but not all OSAS patients are submitted this examination. Nocturnal hypoxemia related to OSAS can induce retinal vessel constriction with a reduction of artero-venous ratio (AVR) evaluated by retinography. Aim of this study was to evaluate in severe OSAS patients a correlation between a severe constriction of AVR index ( 2 ), aged from 35 to 60 years, non smokers, non diabetics, non cardiopathics, non hypertensive, diagnosed for severe OSAS (AHI=43,5±22/h) after a polisomnography, underwent retinography of the two eyes with Topcon TCR NW200 non mydriatic retinal camera. 27/30 patients with a severe constricted AVR Index (
Can nasal-NO be used to differentiate between primary and secondary ciliary dyskinesia?
Authors: Christina Krantz, Andrei Malinovischi, Annika Hollsing, Kjell Alving
Journal: European Respiratory Journal (2011)

Bakground: Nasal nitric oxide (n-NO) has been suggested as a screening test for primary ciliary dyskinesia (PCD) as patients with PCD have lower n-NO levels than healthy controls. Recent studies on n-NO in PCD and secondary ciliary dyskinesia (SCD) show an overlap between these two groups.   Aim:  To investigate in a pilot study if n-NO can differentiate between patients with diagnosed PCD and SCD treated at our centre.   Methods:  n-NO was measured in duplicate by aspiration at 5 ml/s with NIOX Mino in 21 patients with clinically diagnosed PCD (n=12) or SCD (n=9). The electron microscopy (EM) results on brush samples from the nose were available in all subjects.   Results:  Reproducibility of n-NO was good in each patient. A group of patients (n=6) had clearly low n-NO (5-69ppb) compared with the rest (216-857ppb). In the group with low n-NO there were only patients with PCD while in the group with high n-NO there were both patients with SCD and PCD, including 2 with Kartagener9s syndrome. Regarding EM findings, the only 3 subjects with no dyneinarms were in the low n-NO while 8 subjects without structural abnormalities had high n-NO values. The relatively large group with more atypical or inconclusive results was also heterogenous with regard to n-NO levels.   Conclusion:  A low n-NO value had a good positive predictive value for PCD in our material, but some PCD patients had normal n-NO levels. As structural findings on EM and n-NO appear to dissociate in some subjects, we continue to investigate all PCD and SCD patients at our centre including even functional tests of ciliary clearance, to see if n-NO correlates more to the cilia function than structural abnormalities.
Laryngeal involvement in the Dowling-Meara variant of epidermolysis bullosa simplex with keratin mutations of severely disruptive potential
Authors: C.S. Shemanko, H.M. Horn, S.G. Keohane, N. Hepburn, A.I.G. Kerr, D.J. Atherton, M.J. Tidman, E.B. Lane
Journal: British Journal of Dermatology (2000)

The clinical features of the Dowling–Meara variant of epidermolysis bullosa simplex (EBS‐DM) can, in an infant, be indistinguishable from other severe forms of epidermolysis bullosa (EB). Two unrelated infants with no family history of skin disease are described who, within hours of birth, developed extensive blistering of skin and oral mucosae and who both subsequently developed hoarse cries. Despite this superficial resemblance to other forms of EB, electron microscopy revealed a basal cell rupture and keratin aggregates characteristic of EBS‐DM in the skin of both infants and in the vocal cord epithelium of one. Molecular analysis confirmed the diagnosis by identification of mis‐sense point mutations in basal cell keratin genes in both cases. One patient carries a point mutation in keratin 14 (converting arginine at position 125 to histidine) and the other has a novel point mutation in keratin 5 (converting serine at position 181 to proline). Hoarseness is not a well documented feature of EBS‐DM and is usually associated with junctional EB. These two patients demonstrate that the presence of a hoarse cry in an infant affected by severe EB does not necessarily indicate a poor prognosis.
Ribozyme-mediated revision of RNA and DNA
Authors: Meredith B. Long, J.P. Jones, Bruce A. Sullenger, Jonghoe Byun
Journal: Journal of Clinical Investigation (2003)

hepatitis C virus (HCV); internal ribosome entry site (IRES); ribonucleoprotein (RNP); exon-binding site (EBS); intron-binding site (IBS).
THE COLOR OF THE SKIN AS ANALYZED BY SPECTROPHOTOMETRIC METHODS
Authors: Louis A. Brunsting, Charles Sheard
Journal: Journal of Clinical Investigation (1929)

Variation in the superficial blood supply undoubtedly plays a more important r6le in the production of changes in the color of the skin than does an increase or decrease in the pigment.This accounts for the difference in subjects who are fairly well matched otherwise with regard to content of cutaneous pigment.In general, the pigment, in proportion to its amount, prevents the superficial blood from attain- ing visibility.Changes in color in the brunet, attributable to alterations in the circulation in the skin, are less noticeable than the same changes in the blond, and in the negro they are practically negligible.This holds true for the skin of the same thickness, it being quite obvious that the skin of the palms or soles or other hyper- keratotic areas will permit less light to penetrate than will the thin covering of the malar prominence or the dorsum of the hand.The color which the blood imparts to the skin is directly related to the amount or quality of the blood present in the peripheral vessels.The size of the arteries, capillaries, and venules varies with the degree of pressure behind them and with the volume of blood to be accommodated.In conditions of hypertension one would expect more force to be exerted peripherally than normally.In the dependent areas of the body, such as the legs and hands, the elements of gravity and stasis of sluggish flow are added.In cases in which the total blood volume ' The material in this paper was submitted by Dr. Brunsting
Sister Chromatid Exchange and Chromosome Aberration Analysis With the Use of Several Carcinogens and Noncarcinogens: Brief Communication
Authors: N. C. Popescu, D. Turnbull, J. A. DiPaolo
Journal: JNCI Journal of the National Cancer Institute (1977)

Several chemical carcinogens and noncarcinogens were tested for their ability to induce sister chromatid exchanges (SCE) and structural chromosome aberrations in cultured V79-4 Chinese hamster cells. All of the direct-acting carcinogens induced a large increase in SCE frequency. Two chemicals, which are mutagenic in microorganisms but whose carcinogenicity is poorly documented, also increased the frequency of SCE. Carcinogenic polycyclic hydrocarbons caused an increased incidence of SCE only when a metabolizing feeder layer was used, whereas no increase was observed with noncarcinogenic polycyclic hydrocarbons. The other noncarcinogens also did not influence the SCE frequency. Although some chemicals increased the frequency of structural chromosome aberrations, no correlation was found between the frequencies of SCE and aberrations.
Thyroid Function Screening of Psychiatric Inpatient Admissions: A Worthwhile Procedure?
Authors: P Bannister, A Mortimer, L Shapiro, A C P Simms
Journal: Journal of the Royal Society of Medicine (1987)

A thyroid function screening programme of admissions to a general psychiatric service was established. Over a 22-week period 588 patients were admitted and thyroid function tests were performed on 336, a screening rate of 57.1%. Initial investigation showed that 21.3% had a total thyroxine outside the range 75-130 nmol/l. On further investigation only 9 patients (1 thyrotoxic, 8 hypothyroid) had confirmed thyroid disease. In 7 of the 9 patients the disease had been clinically suspected. Thus the screening programme identified only 2 unsuspected cases of thyroid dysfunction and we conclude that this level of detection does not warrant a formal screening programme.
Accelerated Treatment of Breast Cancer
Authors: Frank A. Vicini, Kathy L. Baglan, Larry L. Kestin, Chris Mitchell, Peter Y. Chen, Robert C. Frazier, Greg Edmundson, Neal S. Goldstein, Pamela Benitez, Raywin R. Huang, Alvaro Martinez
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Radiation therapy (RT) restricted to the tumor bed, by means of an interstitial implant, and lasting 4 to 5 days after lumpectomy was prospectively evaluated in early-stage breast cancer patients treated with breast-conserving therapy (BCT). The goals of the study were to determine whether treatment time can be reduced and whether elective treatment of the entire breast is necessary. MATERIALS AND METHODS: Between January 1993 and January 2000, 174 cases of early-stage breast cancer were managed with lumpectomy followed by RT restricted to the tumor bed using an interstitial implant. Each brachytherapy patient was matched with one external-beam RT (ERT) patient derived from a reference group of 1,388 patients treated with standard BCT. Patients were matched for age, tumor size, histology, margins of excision, absence of an extensive intraductal component, nodal status, estrogen receptor status, and tamoxifen use. Median follow-up for both the ERT and brachytherapy groups was 36 months. RESULTS: No statistically significant differences were noted in the 5-year actuarial rates of ipsilateral breast treatment failure or locoregional failure between ERT and brachytherapy patients (1% v 0%, P = .31 and 2% v 1%, P = .63, respectively). In addition, there were no statistically significant differences noted in rates of distant metastasis (6% v 3%, P = .24), disease-free survival (87% v 91%, P = .55), overall survival (90% v 93%, P = .66), or cause-specific survival (97% v 99%, P = .28). CONCLUSION: Accelerated treatment of breast cancer using an interstitial implant to deliver radiation to the tumor bed alone over 4 to 5 days seems to produce 5-year results equivalent to those achieved with conventional ERT. Extended follow-up will be required to determine the long-term efficacy of this treatment approach.
Granule cytotoxic activity and oxidative DNA damage in smoking and non-smoking asthmatics
Authors: Nikolaos Soulitzis, Athanasia Proklou, Eirini Neofytou, Nikoletta Rovina, Eleftherios Zervas, Mina Gaga, Epistimi Kallitsi, Nikolaos Siafakas, Eleni Tzortzaki
Journal: European Respiratory Journal (2013)

Background: Lung cytotoxic mechanisms trigger the release of Perforin and Granzymes, causing oxidative DNA damage that ultimately lead to apoptosis. These effects, although demonstrated in chronic obstructive pulmonary disease (COPD), have not been investigated in patients with asthma and in particular in smoking asthmatics.

Aim: To measure Perforin, Granzyme A, Granzyme B and 8-OHdG expression in sputum from smoking and non-smoking asthmatics, compared to smokers and non-smokers controls.

Methods: Perforin, Granzyme A, Granzyme B and 8-OHdG expression levels were detected by ELISA assays, in induced sputum specimens.

Results: Perforin expression was increased in 40% of smokers and 45% of smoking asthmatics, while only in 7% of asthma patients (p=0.004), compared to controls’ values. In contrast, Granzymes A and B levels were increased in more that 40% of patients in all three groups versus controls. Finally, 8-OHdG levels were elevated in 35% of smoking asthmatics, in 20% of smokers and only in 10% of asthma patients. Statistical analysis revealed a positive correlation between Granzyme A (p<0.001) and Granzyme B (p=0.006) expression levels and the number of pack-years in smoking asthmatic patients.

Conclusions: Asthma cytotoxic immune response is mainly represented by Granzymes A and B, while in smoking asthmatics Perforin and 8-OHdG are additionally involved, resembling the immune response in COPD.
Neurocognitive Development of Children After a Cerebellar Tumor in Infancy: A Longitudinal Study
Authors: Donna R. Copeland, Carl deMoor, Bartlett D. Moore III, Joann L. Ater
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To assess the long-term neuropsychologic effects experienced by children who have tumors in the cerebellum that are diagnosed and treated during infancy. PATIENTS AND METHODS: Twenty-seven children with posterior fossa tumors diagnosed at less than 36 months of age were assessed prospectively with a comprehensive set of age-appropriate tests. Group means and SDs are reported for assessments conducted at diagnosis (analysis 1) and at the most recent follow-up appointment (analysis 2). Cognitive developmental growth curves were derived from the prospective data (analysis 3) using mixed model regression analyses and controlling for age at diagnosis and socioeconomic status. RESULTS: In the first analysis, eight of 11 infants at diagnosis scored within normal limits on all neuropsychologic domains, except for motor skills, which were impaired. In the second analysis, mean scores at the most recent follow-up of 21 of 27 patients were mostly in the normal range; however, group comparisons between those who had (n = 7) and had not (n = 14) been treated with cranial radiation therapy (CRT) showed that patients in the irradiated (CRT) group scored significantly lower than those in the nonirradiated (No-CRT) group on verbal intelligence quotient (IQ) and in the motor domain. In the third analysis (growth curves of CRT and No-CRT groups), statistically significant differences in slope were found on verbal IQ, performance IQ, perceptual-motor skills, language, and attention/executive skills. Slopes on the fine-motor domain were similar; both groups declined at approximately the same rate. CONCLUSION: Neurocognitive development and outcome of children with cerebellar tumors diagnosed in infancy is very positive among those who were treated with surgery and chemotherapy. Declines in performance across time were minimal, and scores tended to remain within normal limits. By itself, a cerebellar tumor in infancy does not seem to have a significant impact on children. However, those who received CRT as part of their treatment are likely to have neurocognitive and psychosocial deficits that require remediational interventions.
Abstract 317: Beta3 Integrin-mediated CTGF Expression in Cardiac Hypertrophy
Authors: Kamala P Sundararaj, Dorea L Pleasant, Sundaravadival Balasubramanian, Dhandapani Kuppuswamy
Journal: Circulation Research (2014)

Connective Tissue Growth Factor (CTGF/CCN2) is a fibrotic mediator overexpressed in human atherosclerotic lesions, myocardial infarction and hypertension. CTGF regulates ECM deposition, fibrosis, wound repair and angiogenesis. Our preliminary studies using wild type (WT) and global 3 integrin knockout (3-/-) mice show for the first time that pressure overload (PO) by transverse aortic constriction (TAC) induces both CTGF and 3 integrin expression in WT mice and that 3 integrin is a prerequisite for the PO-induced CTGF expression. Since both the major cells, cardiomyocyte (CM) and cardiac fibroblast (CFb) have been shown to express CTGF, exploring the primary source for the 3 integrin mediated CTGF expression is expected to identify potential targets for fibrosis. Therefore, the main focus of this proposed study is to use CM specific β3 integrin KO mice with preserved β3-integrin function in CFb as well as CFb specific β3 integrin KO mice with preserved β3-integrin function in CM and evaluate which heart cell type contributes to β3-integrin-mediated PO-induced CTGF production and ECM accumulation. Furthermore, using cells isolated from these mice, we will perform in vitro studies to explore the mechanism by which β3-integrin mediates CTGF secretion by analyzing specific nonreceptor tyrosine kinases and transcription factors.
Analysis of C-reactive protein and fibrinogen as possible predictors of secondary fibrosis in pulmonary tuberculosis
Authors: Besim Prnjavorac, Adlija Cauševic, Sabina Semiz, Tanja Dujic, Tamer Bego, Nedzada Ireijz, Rifat Sejdinovic
Journal: European Respiratory Journal (2011)

Aim: To study the influence of C-reactive protein (CRP) level in the blood, fibrinogen level and general inflammatory syndrome as the predictors of development of secondary fibrosis in patients with pulmonary tuberculosis (TB).

Methods: Concentration of CRP, fibrinogen level was measured using immunoturbidimetric methodIncluding criteria was presentation of TB process in both lungs, as the sign of widespread TB process.

Results: We examined 85 patients treated in one year. Mean CRP level was 22,6 mg/mL, range 5-245 mg/mL; normal level (up to 8 mg/mL) was measured in 23,4% patients, medium level (9-20 mg/mL) was measured in 31,3% patients, high level (21-50 mg/mL) were measured in 26,2% patients, and in 23,7% patients CRP were higher than 50 mg/mL. Average fibrinogen level in whole group was 6,9 g/L (SD 5,8). Normal level of fibrinogen (up to 4 g/L) were measured in 6,4% of patients; 4,1-1,0 g/L were measured in 24,6% patients, 10,1-20 g/L were measured in 31,1% patient and level more than 20 g/L were measured in 37,9% patients. Using statistic method of partial correlation statistical significane at level p<0,05 was shown between them. Correlation of CRP and fibrinogen level with appearance of fibrosis on X-ray of the lung was shown. Thereafter, closer correlation was shown with fibrinogen and fibrosis than with CRP and fibrosis.

Conclusion: Predicted value of CRP and fibrinogen for pulmonary fibrosis was shown in TB patients. So, attenuation of fibrosis development, possible with antifibroblastic activity of pentoxyphyllin, should be taken in consideration, for prevention of widespread development of lung fibrosis in these patients.
Poor efficacy and tolerability of <scp>R‐CHOP</scp> in relapsed/refractory chronic lymphocytic leukemia and <scp>R</scp>ichter transformation
Authors: Petra Langerbeins, Raymonde Busch, Nadine Anheier, Jan Dürig, Manuela Bergmann, Maria‐Elisabeth Goebeler, Hans‐Jürgen Hurtz, Martina B. Stauch, Stephan Stilgenbauer, Hartmut Döhner, Anna‐Maria Fink, Paula Cramer, Kirsten Fischer, Clemens‐Martin Wendtner, Michael Hallek, Barbara Eichhorst
Journal: American Journal of Hematology (2014)

This phase II trial evaluated efficacy and tolerability of R‐CHOP for up to 8 courses in Richter transformation (RT) and up to 6 courses in CLL plus autoimmune cytopenia (AIC) or high‐risk (HR) features. HR was defined as fludarabine‐refractoriness or early relapse (&lt;36 months) after fludarabine‐based treatment; 26 patients were included as HR, 19 patients had AIC, and 15 patients had RT. In the HR cohort, overall response rate was 54%, progression‐free and overall survival were 9 and 21 months. In AIC patients overall response rate was 74%, progression‐free and overall‐survival were 10 and 41 months, respectively, and median increase in hemoglobin was 3.4 g/L. RT patients responded in 67%, progression‐free was 10 and overall survival 21 months. The most common adverse events were hematologic toxicities in 92%. Severe infections occurred in 28%. Treatment was discontinued early in 45% of all patients mainly as a result of toxicity. This trial shows that R‐CHOP has no role in treating complicated CLL. R‐CHOP is associated with significant toxicities and fairly low efficacy compared with almost every other CLL‐regimen. In RT, it might still be used as an induction therapy before allogeneic stem cell transplantation. Am. J. Hematol. 89:E239–E243, 2014. © 2014 Wiley Periodicals, Inc.
Biodistribution and pharmacokinetics of radiolabeled trastuzumab in HER2-positive metastatic breast cancer
Authors: M. N. Lub-De Hooge, P. J. Perik, J. A. Gietema, P. L. Jager, S. Jonkman, J. G. W. Kosterink, D.-J. J. Van Veldhuisen, W. T. A. Van der Graaf, D. T. H. Sleijfer, E. G. E. De Vries
Journal: Journal of Clinical Oncology (2004)

3063 Background: Trastuzumab combined with chemotherapy can induce remissions in HER2 positive metastatic breast cancer (MBC), but also cardiac dysfunction. The aim of this study is to evaluate whether scintigraphy using radiolabeled trastuzumab can predict cardiotoxicity, and identify tumor lesions and response. Methods: In an ongoing study, patients (pts) with HER2 positive MBC, suitable for Herceptin (d1, 8 and 15) plus paclitaxel (d1), underwent gammacamera imaging and blood sampling from 15 min to 7d after injection of 150 MBq 111In-DTPA-trastuzumab, prior to and after 4 therapy cycles. In known lesions (CT/ultrasound/Xray/bone scan), the degree of 111In-DTPA-trastuzumab tumor uptake was expressed as tumor/ background ratio (tumor vs. background uptake intensity) and as % injected dose index (tumor vs. total body (TB) counts). Results: Up to now, 11 pts have been enrolled. Plasma T½α was 14.7±6.97h, T½β 115.9±46.71h (n=8). Variable uptake in tumor lesions was present in all pts after 5 and 7d, starting from d1. At d1, tumor/background ratio was 2.0 (1.4–3.5), 0.7% TB (0.1–5.5%) uptake. At d7 these figures were 2.1 (1.7–9.3) and 0.9%TB (0.2–5.5%). One or multiple lesions were visualized in every pt, although not all known lesions. In 5 pts previously unknown lesions were found. Visualization of liver metastases was difficult (missed in 2/ 6 pts), due to high liver uptake (d5 24.3%, 17.4–33.6%). Uptake in organs such as, spleen and kidneys, and bloodpool activity decreased between d1 and 7, while tumor and liver uptake increased. Myocardial uptake occurred in 1 pt, who had cardiac arrhythmias prior to treatment. Conclusions: Preliminary results show that radiolabeled trastuzumab scintigraphy can identify HER2 positive tumor lesions, which may assist in identifying metastases and in predicting tumor response. Defining predictive value for cardiotoxicity and tumor response requires a larger pt number. This study continues to recruit. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb; Roche Bristol-Myers Squibb; Roche