tbuckley/cabot-search huggingface dataset:
Association Between Intima-Media Thickness and Wall Shear Stress in Common Carotid Arteries in Healthy Male Subjects
Authors: Agostino Gnasso, Claudio Carallo, Concetta Irace, Vitaliano Spagnuolo, Giuseppina De Novara, Pier Luigi Mattioli, Arturo Pujia
Journal: Circulation (1996)

Atherosclerotic lesions lie in regions of low wall shear stress. No relationship between wall shear stress and intima-media thickness in vivo has been reported. Aims of the present study were to verify the reproducibility of wall shear stress measurement in vivo and to evaluate its association with intima-media thickness in the common carotid artery in healthy subjects.Wall shear stress was calculated according to the following formula: Shear Stress = Blood Viscosity x Blood Velocity/Internal Diameter. Blood viscosity was measured by use of a cone/plate viscometer. Blood velocity, internal diameter, and intima-media thickness were measured by high-resolution echo Doppler. Twenty-one healthy male subjects were investigated. Peak and mean shear stress values were 29.5 +/- 8.2 and 12.1 +/- 3.1 dynes/cm-2 (mean +/- SD), respectively. Peak shear stress was inversely related to intima-media thickness (r = .62), age (r = .77), systolic blood pressure (r = .61), and body mass index (r = .59) (P < .001 for all coefficients). Mean shear stress yielded similar results. The relationship between shear stress and intima-media thickness was independent of age, blood pressure, and body mass index. The reproducibility, calculated by Kendall's W test, was statistically significant.Our results demonstrate that common carotid artery wall shear stress measurement in vivo is reproducible. It inversely relates to intima-media thickness, age, systolic blood pressure, and body mass index. These findings confirm in vivo the role of shear stress in intima-media thickening.
Bendamustine and Rituximab in Relapsed and Refractory Hairy Cell Leukemia
Authors: Mauricio Burotto, Maryalice Stetler-Stevenson, Evgeny Arons, Hong Zhou, Wyndham Wilson, Robert J. Kreitman
Journal: Clinical Cancer Research (2013)

To determine tolerability and for the first time explore efficacy of bendamustine-rituximab (BR) in multiply relapsed/refractory hairy cell leukemia (HCL), using two different dose levels of bendamustine.
PREVENTION OF BICYCLE-RELATED INJURIES: Helmets, Education, and Legislation
Authors: Frederick P. Rivara, Diane C. Thompson, Matthew Q. Patterson, Robert S. Thompson
Journal: Annual Review of Public Health (1998)

▪ Abstract Efforts to reduce the toll of bicycle-related head injuries illustrate how the basic public health principles of surveillance, epidemiologic study, intervention, and evaluation can have a substantial impact on an injury problem, using a variety of injury-prevention strategies. Head injuries are the leading cause of serious morbidity and mortality from bicycle crashes. Helmets have been shown to reduce bicycle-related head injuries for cyclists of all ages involved in all types of crashes including those with motor vehicles. Helmet use has been promoted using educational campaigns, helmet subsidies, and legislation. Careful evaluation of these strategies has shown that these interventions increase helmet use and decrease the incidence of bicycle injuries. The model developed for the prevention of bicycle injuries is widely applicable to other injury problems.
Invariant Natural Killer T Cells and TGF-β Attenuate Anti-GBM Glomerulonephritis
Authors: Laurent Mesnard, Alexandre D.C. Keller, Marie-Laure Michel, Sophie Vandermeersch, Ce[Combining Acute Accent]dric Rafat, Emmanuel Letavernier, Yves Tillet, Eric Rondeau, Maria C. Leite-de-Moraes
Journal: Journal of the American Society of Nephrology (2009)

Invariant natural killer T (iNKT) cells represent a particular subset of T lymphocytes capable of producing several cytokines, which exert regulatory or effector functions, following stimulation of the T cell receptor. In this study, we investigated the influence of iNKT cells on the development of experimental anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). After injection of anti-GBM serum, the number of kidney iNKT cells rapidly increased. iNKT cell-deficient mice (Jα18−/−) injected with anti-GBM serum demonstrated worse renal function, increased proteinuria, and greater glomerular and tubular injury compared with similarly treated wild-type mice. We did not detect significant differences in Th1/Th2 polarization in renal tissue that might have explained the severity of disease in Jα18−/− mice. Interestingly, expression of both TGF-β and TGF-β-induced (TGFBI) mRNA was higher in wild-type kidneys compared with Jα18−/− kidneys, suggesting a possible protective role for TGF-β in anti-GBM GN. Administration of an anti-TGF-β neutralizing antibody significantly enhanced the severity of disease in wild-type, but not Jα18−/−, mice. In conclusion, in experimental anti-GBM GN, iNKT cells attenuate disease severity and TGF-β has a renoprotective role.
Evolving anticancer drug valproic acid: Insights into the mechanism and clinical studies
Authors: Roman A. Blaheta, Martin Michaelis, Pablo Hernáiz Driever, Jindrich Cinatl
Journal: Medicinal Research Reviews (2005)

Abstract The short chain fatty acid valproic acid (VPA) and VPA‐analogs modulate the biology of diverse tumor cell entities by inducing differentiation, inhibiting proliferation, increasing apoptosis, and immunogenicity and by decreasing metastatic and angiogenetic potential. This review updates an earlier one in 2002, reflecting the interest in VPA as a potent anticancer drug. A number of in vitro studies show that the types of known tumor cells susceptible to VPA is steadily increasing. Of special note is the strong antineoplastic activity of VPA in chemoresistant cancer cells. A novel and promising approach is combining VPA with other drugs to achieve a broad therapeutic index. Clinical studies are underway and the preliminary results indicate that VPA alone or in combination offers a promising avenue of treatment, both in solid and hematopoetic malignancies. © 2005 Wiley Periodicals, Inc.
Alterations in cardiac gene expression during the transition from stable hypertrophy to heart failure. Marked upregulation of genes encoding extracellular matrix components.
Authors: M O Boluyt, L O'Neill, A L Meredith, O H Bing, W W Brooks, C H Conrad, M T Crow, E G Lakatta
Journal: Circulation Research (1994)

The failing heart is characterized by impaired cardiac muscle function and increased interstitial fibrosis. Our purpose was to determine whether the functional impairment of the failing heart is associated with changes in levels of mRNA encoding proteins that modulate parameters of contraction and relaxation and whether the increased fibrosis observed in the failing heart is related to elevated expression of genes encoding extracellular matrix components. We studied hearts of 18- to 24-month-old spontaneously hypertensive rats with signs and symptoms of heart failure (SHR-F) or without evidence of failure (SHR-NF) and of age-matched normotensive Wistar-Kyoto (WKY) rats. Compared with WKY rats, SHR-NF exhibited left ventricular (LV) hypertrophy (2.2-fold) and right ventricular (RV) hypertrophy (1.5-fold), whereas SHR-F were characterized by comparable LV hypertrophy (2.1-fold) and augmented RV hypertrophy (2.4-fold; all P &lt; .01). Total RNA was isolated from ventricles and subjected to Northern blot analysis. In SHR-F hearts, the level of alpha-myosin heavy chain mRNA was decreased in both ventricles to 1/3 and 1/5 of the SHR-NF and WKY values, respectively (both P &lt; .01). Levels of beta-myosin heavy chain, alpha-cardiac actin, and myosin light chain-2 mRNAs were not significantly altered in hearts of SHR-NF or SHR-F. Levels of alpha-skeletal actin were twofold greater in SHR-NF hearts compared with WKY hearts and were intermediate in SHR-F hearts. Levels of atrial natriuretic factor (ANF) mRNA were elevated threefold in the LV of SHR-NF (P &lt; .05) but were not significantly increased in the RV of SHR-NF compared with WKY rats. During the transition to failure (SHR-F versus SHR-NF), ANF mRNA levels increased an additional 1.6-fold in the LV and were elevated 4.7-fold in the RV (both P &lt; .05). Levels of sarcoplasmic reticulum Ca(2+)-ATPase (SRCA) mRNA were maintained in the LV of hypertensive and failing hearts at levels not significantly different from WKY values. In contrast, the level of RV SRCA mRNA was 24% less in SHR-NF compared with WKY rats, and during the transition to failure, this difference was not significantly exacerbated (29% less than the WKY value). The levels of fibronectin and pro-alpha 1(I) and pro-alpha 1(III) collagen mRNAs were not significantly elevated in either ventricle of the SHR-NF group but were fourfold to fivefold higher in both ventricles of SHR-F (all P &lt; .05).(ABSTRACT TRUNCATED AT 400 WORDS)
The characterization of upper-room ultraviolet germicidal irradiation in inactivating airborne microorganisms.
Authors: Gwangpyo Ko, Melvin W First, Harriet A Burge
Journal: Environmental Health Perspectives (2002)

In this study, we explored the efficacy of upper-room ultraviolet germicidal irradiation (UVGI) in reducing the concentration of Serratia marcescens and Mycobacterium bovis bacille Calmette-Guérin (BCG) aerosols in enclosed places. We constructed a facility (4.5 m x 3 m x 2.9 m) in which both ceiling- and wall-mounted UV fixtures (UV output: 10W and 5W respectively) were installed. The use of ceiling- and wall-mounted UV fixtures (total UV output: 15W) without mixing fan reduced the concentration of S. marcescens aerosols by 46% (range: 22-80%) at 2 air changes per hour (ACH) and 53% (range: 40-68%) at 6 ACH. The use of ceiling- and wall-mounted UV fixtures with mixing fan increased the UV effectiveness in inactivating S. marcescens aerosols to 62% (range: 50-78%) at 2 ACH and to 86% (81-89%) at 6 ACH. For BCG aerosols, UV effectiveness in inactivating BCG aerosols at 6 ACH were 52% (range: 11-69%) by ceiling-mounted UV fixture only (total UV output: 10W) and 64% (51-83%) by both ceiling- and wall-mounted UV fixtures (total UV output: 15W). Our results indicated that the equivalent ventilation rate attributable to upper-room UVGI for BCG aerosols ranged from 1 ACH to 22 ACH for ceiling-mounted UV fixtures and from 6.4 ACH to 28.5 ACH for ceiling- and wall-mounted UV fixtures. Both generalized linear and generalized additive models were fitted to all our data. The regression results indicated that the number of UV fixtures, use of mixing fan, and air exchange rate significantly affected UV effectiveness (p < 0.01, 0.01, 0.01 respectively). However, the strain difference (S. marcescens vs. BCG) appeared less important in UV effectiveness (p = 0.26). Our results also indicated that UV effectiveness increased at higher temperature ((italic)p(/italic) < 0.01), lower dry-bulb temperature ((italic)p(/italic) = 0.21), and colder air from a supply grill located near the ceiling (p = 0.22).
Intestinal malabsorption and the skin.
Authors: J Marks, S Shuster
Journal: Gut (1971)

<h3>Abstract</h3> The present study aims to investigate the genomic variability and epidemiology of SARS-CoV-2 in Pakistan along with their role in the spread and severity of infection during the three waves of COVID-19. A total of 453 genomic sequences of Pakistani SARS-CoV-2 were retrieved from GISAID and subjected to MAFFT-based alignment and QC check which resulted in removal of 53 samples. The remaining 400 samples were subjected to Pangolin-based genomic lineage identification. And to infer our SARS-CoV-2 time-scaled and divergence phylogenetic trees, 3,804 selected global reference sequences plus 400 Pakistani samples were used for the Nextstrain analysis with Wuhan/Hu-1/2019, as reference genome. Finally, maximum likelihood based phylogenetic tree was built by using the Nextstrain &amp; coverage map was created by employing Nextclade. And by using the amino acid subsitutions the maximum likelihood phylogenetic trees were developed for each wave, separately. Our results reveal the circulation of 29 lineages, belonging to following 7 clades G, GH, GR, GRY, L, O, &amp; S in the three waves. From first wave, 16 genomic lineages of SARS-CoV-2 were identified with B.1(24.7%), B.1.36(18.8%), &amp; B.1.471(18.8%) as the most prevalent lineages respectively. The second wave data showed 18 lineages, 10 of which were overlapping with the first wave suggesting that those variants could not be contained during the first wave. In this wave, a new lineage, AE.4, was reported from Pakistan for the very first time in the world. However, B.1.36 (17.8%), B.1.36.31 (11.9%), B.1.1.7 (8.5%) &amp; B.1.1.1 (5.9%) were the major lineages in second wave. Third wave data showed the presence of 9 lineages with Alpha/B.1.1.7 (72.7%), Beta/B.1.351 (12.99%), &amp; Delta/B.1.617.2 (10.39%) as the most predominant variants. It is suggested that these VOCs should be contained at the earliest in order to prevent any devastating outbreak of SARS-CoV-2 in the country.
Alternative splicing of mouse transcription factors affects their DNA-binding domain architecture and is tissue specific.
Authors: Bahar Taneri, Ben Snyder, Alexey Novoradovsky, Terry Gaasterland
Journal: Genome biology (2004)

Abstract Background Analyzing proteins in the context of all available genome and transcript sequence data has the potential to reveal functional properties not accessible through protein sequence analysis alone. To analyze the impact of alternative splicing on transcription factor (TF) protein structure, we constructed a comprehensive database of splice variants in the mouse transcriptome, called MouSDB3 containing 461 TF loci. Results Our analysis revealed that 62% of these loci in MouSDB3 have variant exons, compared to 29% of all loci. These variant TF loci contain a total of 324 alternative exons, of which 23% are in-frame. When excluded, 80% of in-frame alternative exons alter the domain architecture of the protein as computed by SMART (simple modular architecture research tool). Sixty-eight % of these exons directly affect the coding regions of domains important for TF function. Seventy-five % of the domains affected are DNA-binding domains. Tissue distribution analyses of variant mouse TFs reveal that they have more alternatively spliced forms in 14 of the 18 tissues analyzed when compared to all the loci in MouSDB3. Further, TF isoforms are homogenous within a given single tissue and are heterogeneous across different tissues, indicating their tissue specificity. Conclusions Our study provides quantitative evidence that alternative splicing preferentially adds or deletes domains important to the DNA-binding function of the TFs. Analyses described here reveal the presence of tissue-specific alternative splicing throughout the mouse transcriptome. Our findings provide significant biological insights into control of transcription and regulation of tissue-specific gene expression by alternative splicing via creation of tissue-specific TF isoforms.
Physiological Evaluation of Chronic Right Ventricular Bypass
Authors: C. GRANT LAFARGE, MICHAEL BANKOLE, WILLIAM F. BERNHARD
Journal: Circulation (1971)

Investigations with an implantable left ventricular (LV) assist pump indicated inadequate circulatory support in the presence of induced ventricular fibrillation (VF). Consequently, a right ventricular (RV) bypass pump was developed to provide a stable pulmonary blood flow. This report evaluates the physiological effects of the RV pump alone and in conjunction with an LV pump. Eleven calves have been evaluated by standard cardiac catheterization techniques during chronic pumping (1 to 85 days, mean 30 days, and continuing). Pressures, flows, and RV and LV function were monitored with transducer-tipped catheters and angiography. Effective pulmonary compliance was also measured. The RV bypass studies revealed (1) pump capability up to 8 L/min, reducing RV pressure and work to zero, (2) pulmonary artery pressure not significantly increased (20 to 40 mm Hg), (3) pulmonary compliance identical with sham-operated calves, and (4) no pathological changes noted in lungs. Data suggest that biventricular bypass pumps will provide chronic circulatory support during VF or biventricular failure.
The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barré syndrome
Authors: Peggy C.R. Godschalk, Astrid P. Heikema, Michel Gilbert, Tomoko Komagamine, C. Wim Ang, Jobine Glerum, Denis Brochu, Jianjun Li, Nobuhiro Yuki, Bart C. Jacobs, Alex van Belkum, Hubert P. Endtz
Journal: Journal of Clinical Investigation (2004)

Molecular mimicry of Campylobacter jejuni lipo-oligosaccharides (LOS) with gangliosides in nervous tissue is considered to induce cross-reactive antibodies that lead to Guillain-Barre syndrome (GBS), an acute polyneuropathy. To determine whether specific bacterial genes are crucial for the biosynthesis of ganglioside-like structures and the induction of anti-ganglioside antibodies, we characterized the C. jejuni LOS biosynthesis gene locus in GBS-associated and control strains. We demonstrated that specific types of the LOS biosynthesis gene locus are associated with GBS and with the expression of ganglioside-mimicking structures. Campylobacter knockout mutants of 2 potential GBS marker genes, both involved in LOS sialylation, expressed truncated LOS structures without sialic acid, showed reduced reactivity with GBS patient serum, and failed to induce an anti-ganglioside antibody response in mice. We demonstrate, for the first time, to our knowledge, that specific bacterial genes are crucial for the induction of anti-ganglioside antibodies.
Debate Over Institutional Review Boards Continues as Alternative Options Emerge
Authors: C. McNeil
Journal: JNCI Journal of the National Cancer Institute (2007)

O n Jan. 1, the University of Minnesota launched a major overhaul of its institutional review boards (IRBs) with the goal of increasing efficiency, quality, and — most importantly for many IRB critics — the speed with which it reviews new clinical trial protocols. The reforms represent one approach to fi xing the problems that have been plaguing IRBs everywhere for more than a decade. Charged with protecting human research subjects, IRBs have been facing increasing workloads, diffi culty attracting qualified members, and lack of expertise in specifi c areas of medicine. The University of Minnesota’s local reforms buck the growing trend toward use of external or “central” IRBs to solve these problems. Outsourcing review to central IRBs, including the independent, for-profi t boards that charge a fee, is increasingly common and has the explicit support of federal agencies including the Offi ce for Human Research Protections (OHRP), the U.S. Food and Drug Admi nistration, and the National Cancer Institute. Nevertheless, the debate over local versus central review continues, as does the search for alternative models that might include the advantages of both. What happens in Minnesota in the next few years, as well as with the growing number of alternatives, will be closely watched by the entire clinical trial community. At the University of Minnesota, the new IRB has started meeting once a week rather than once a month. Several boards have been consolidated into one, with its members rotating according to the expertise needed. Its members, all senior investigators, will be paid. These reforms and others — the use of electronic forms and assistance with applications, for example — should speed up the clinical research process, improve the expertise of the review, and lessen pressure to use central IRBs, said Richard Bianco , associate vice president for research. Over the next few years, he will be collecting data to help gauge the success of this approach, including the time it takes for each stage of the process; for example, how long it takes the IRB staff to present the application to the board members, the time it takes the IRB to approve the trial with stipulations, and the total time to fi nal approval. “I don’t believe our system of local reviews is seriously fl awed,” Bianco said, speaking at a national conference on IRBs convened by OHRP and other national groups last November. “Our patients and subjects can best be served by continuing to strengthen our local IRBs.”
Primary cirrhotic hepatocytes resist TGF$beta;-induced apoptosis through a ROS-dependent mechanism
Authors: Dalliah Mashon Black, Mark A. Bird, Charles M. Samson, Suzanne Lyman, Patty A. Lange, Laura W. Schrum, Ting Qian, J. J. Lemasters, David A. Brenner, Richard A. Rippe, Kevin E. Behrns
Journal: Journal of Hepatology (2004)
Idiopathic retroperitoneal fibrosis.
Authors: D S Keith, T S Larson
Journal: Journal of the American Society of Nephrology (1993)

Herein is described a case report of urinary tract obstruction due to idiopathic retroperitoneal fibrosis (IRF) in a 43-year-old man. Recent studies suggest that IRF fits into the broader pathologic heading of chronic periaortitis. Although there may be more than one pathophysiologic mechanism, growing evidence suggests that many cases of IRF are due to an autoallergic reaction to lipid material in the atheromatous aorta. Computed tomographic scanning has supplanted excretory and retrograde urography in the diagnosis of this condition. Ureterolysis and steroids remain the mainstays in the treatment of IRF. Even after successful decompression of urinary obstruction, long-term follow-up is required in these patients because of the possibility of other complications such as vena caval or duodenal obstruction.