tbuckley/cabot-search huggingface dataset:
Interactions between endothelial nitric oxide synthase and sex hormones in vascular protection in mice
Authors: Jeffrey B. Hodgin, Joshua W. Knowles, Hyung-Suk Kim, Oliver Smithies, Nobuyo Maeda
Journal: Journal of Clinical Investigation (2002)

The vasculoprotective effects of sex hormones, particularly estrogens, have been attributed to their ability to increase the bioavailability of nitric oxide through activation of endothelial nitric oxide synthase (eNOS). To dissect the relative contribution in vivo of eNOS, sex hormones, and their interaction in two complex vascular phenotypes, hypertension and atherosclerosis, we used mice doubly deficient in eNOS and apoE (nnee) or lacking only apoE (NNee). Females and males were gonadectomized at 1 month of age and implanted either with control pellets or pellets releasing 17beta-estradiol (E2). Hormonally intact nnee mice have elevated blood pressure (BP) and increased atherosclerosis compared with NNee mice, but on removal of gonads, BP and atherosclerosis decreased significantly in nnee mice but not in NNee mice. Three months of treatment with exogenous E2 dramatically reduced atherosclerosis and significantly lowered BP in both NNee and nnee mice compared with animals treated with control pellets. Thus exogenous E2 has strong BP-lowering and atheroprotective effects in apoE-deficient mice, but eNOS is not essential for either effect. Endogenous sex hormones, on the other hand, cause significant damage to the vasculature in the absence of eNOS, but these effects are overridden by interactions between eNOS and sex hormones.
Patient-ventilator interaction and inspiratory effort during pressure support ventilation in patients with different pathologies
Authors: S Nava, C Bruschi, C Fracchia, A Braschi, F Rubini
Journal: European Respiratory Journal (1997)

The aim of this study was to evaluate whether pressure support ventilation (PSV) requires different diaphragmatic efforts and patient-ventilator matching, according to the underlying disease. Four groups of patients requiring PSV were studied: Group A, recovering from an episode of acute respiratory failure due to adult respiratory distress syndrome (ARDS); Group B, with postsurgical complications; and two subsets of chronic obstructive pulmonary disease (COPD) patients, with "normal" static compliance of the respiratory system (Cst,rs) (Group C) or elevated Cst,rs (Group D). Ventilatory pattern, transdiaphragmatic pressure (Pdi), the pressure-time product of the diaphragm (PTPdi), static (PEEPi,stat) and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn), Cst,rs and resistance of the total respiratory system (Rrs) were recorded. The matching between patient and ventilator was analysed, recording the number of "ineffective efforts" (inspiratory efforts not efficient enough to trigger a new ventilator cycle, despite a positive deflection in Pdi). A satisfactory blood gas equilibrium arterial oxygen saturation (Sa,O2 &gt; 93%, with a pH &gt; 7.32) was obtained in the various groups with different levels of PSV. Minute ventilation was found to be significantly higher in Groups A and B, due to the longer expiratory time (tE) in the COPD groups. Group A (2 out of 7), Group B (3 out of 7), Group C (3 out of 5) patients showed sporadic "ineffective efforts". All Group D patients manifested continuous mismatching with the ventilator, so that the pressure-time product of the diaphragm per minute (PTPdi/min), reflecting the metabolic work of the diaphragm, was not different in the four groups. Tidal volume and the spontaneous inspiratory efforts were similar in the four groups, but the number of breaths delivered by the ventilator was significantly higher in Groups A and B. The application of different levels of pressure support ventilation in patients with acute respiratory failure due to different pathologies, led them to breathe with comparable pressure time product of the diaphragm. The majority of the patients showed mismatching with the ventilator, although this effect was more pronounced in the groups with chronic obstructive pulmonary disease.
Detection of chronic obstructive pulmonary disease (COPD) in patients with cardio-vascular system pathology
Authors: Daria Mihailichenko, Tetyana Pertseva
Journal: European Respiratory Journal (2013)

The combination of COPD and heart failure (HF) presents many diagnostic challenges. It is very actual for elderly patients with co-morbidities. Evaluation of cardiac and pulmonary function is often problematic and occasionally misleading. COPD very often can be under-diagnosed and under-treated in the elderly population. Beta-blockers are one of the most widely prescribed class of drugs to treat HF, but these drugs in COPD patients might induce bronchospasm and worsen lung function.

Aims : Screening for COPD using spirometry in hospitalized patients of elderly groups with exacerbation of cardiovascular disease (HF, coronary artery disease (CAD), arterial hypertension), associated with worsening of dyspnea.

Materials and Methods: We estimated the function of external respiration by standardized spirometry in 78 hospitalized patients (age – 67,3±7,4 yrs, female – 55 (70,5%), male – 23 (29,5%)). Measurements included clinical status, spirometry with reversibility test, chest roentgenography for pulmonary evaluation.

Results: All participants were divided into three groups (results are presented in Table) 43 (55,1%) hospitalized patient hadn’t any violation of spirometry data. 22 (28,2%) had obstruction, 13 (16,7%) patients had newly detected airflow obstruction and detected COPD, which can leads to dyspnea worsening and impact on cardiovascular disease.

View this table:



Conclusion : Function of external respiration should be estimated in each patient of elderly group with worsening of CAD, who has worsening of dyspnea, for early diagnosis of COPD.
hNaa10p contributes to tumorigenesis by facilitating DNMT1-mediated tumor suppressor gene silencing
Authors: Chung-Fan Lee, Derick S.-C. Ou, Sung-Bau Lee, Liang-Hao Chang, Ruo-Kai Lin, Ying-Shiuan Li, Anup K. Upadhyay, Xiaodong Cheng, Yi-Ching Wang, Han-Shui Hsu, Michael Hsiao, Cheng-Wen Wu, Li-Jung Juan
Journal: Journal of Clinical Investigation (2010)

Hypermethylation-mediated tumor suppressor gene silencing plays a crucial role in tumorigenesis. Understanding its underlying mechanism is essential for cancer treatment. Previous studies on human N-alpha-acetyltransferase 10, NatA catalytic subunit (hNaa10p; also known as human arrest-defective 1 [hARD1]), have generated conflicting results with regard to its role in tumorigenesis. Here we provide multiple lines of evidence indicating that it is oncogenic. We have shown that hNaa10p overexpression correlated with poor survival of human lung cancer patients. In vitro, enforced expression of hNaa10p was sufficient to cause cellular transformation, and siRNA-mediated depletion of hNaa10p impaired cancer cell proliferation in colony assays and xenograft studies. The oncogenic potential of hNaa10p depended on its interaction with DNA methyltransferase 1 (DNMT1). Mechanistically, hNaa10p positively regulated DNMT1 enzymatic activity by facilitating its binding to DNA in vitro and its recruitment to promoters of tumor suppressor genes, such as E-cadherin, in vivo. Consistent with this, interaction between hNaa10p and DNMT1 was required for E-cadherin silencing through promoter CpG methylation, and E-cadherin repression contributed to the oncogenic effects of hNaa10p. Together, our data not only establish hNaa10p as an oncoprotein, but also reveal that it contributes to oncogenesis through modulation of DNMT1 function.
Course of Visual Decline in Relation to the Best1 Genotype in Vitelliform Macular Dystrophy
Authors: Judith C. Booij, Camiel J.F. Boon, Mary J. van Schooneveld, Jacoline B. ten Brink, Arne Bakker, Paulus T.V.M. de Jong, Carel B. Hoyng, Arthur A.B. Bergen, Caroline C.W. Klaver
Journal: Ophthalmology (2010)
Characterization of a novel cellular defect in patients with phenotypic homozygous familial hypercholesterolemia
Authors: Dennis Norman, Xi-Ming Sun, Mafalda Bourbon, Brian L. Knight, Rossitza P. Naoumova, Anne K. Soutar
Journal: Journal of Clinical Investigation (1999)

Familial hypercholesterolemia (FH) is characterized by a raised concentration of LDL in plasma that results in a significantly increased risk of premature atherosclerosis. In FH, impaired removal of LDL from the circulation results from inherited mutations in the LDL receptor gene or, more rarely, in the gene for apo B, the ligand for the LDL receptor. We have identified two unrelated clinically homozygous FH patients whose cells exhibit no measurable degradation of LDL in culture. Extensive analysis of DNA and mRNA revealed no defect in the LDL receptor, and alleles of the LDL receptor or apo B genes do not cosegregate with hypercholesterolemia in these families. FACS® analysis of binding and uptake of fluorescent LDL or anti–LDL receptor antibodies showed that LDL receptors are on the cell surface and bind LDL normally, but fail to be internalized, suggesting that some component of endocytosis through clathrin-coated pits is defective. Internalization of the transferrin receptor occurs normally, suggesting that the defective gene product may interact specifically with the LDL receptor internalization signal. Identification of the defective gene will aid genetic diagnosis of other hypercholesterolemic patients and elucidate the mechanism by which LDL receptors are internalized.
Genetic Ablation of Orexin Neurons in Mice Results in Narcolepsy, Hypophagia, and Obesity
Authors: Junko Hara, Carsten T. Beuckmann, Tadahiro Nambu, Jon T. Willie, Richard M. Chemelli, Christopher M. Sinton, Fumihiro Sugiyama, Ken-ichi Yagami, Katsutoshi Goto, Masashi Yanagisawa, Takeshi Sakurai
Journal: Neuron (2001)
Role of the liver in small-solute transport during peritoneal dialysis.
Authors: M F Flessner, R L Dedrick
Journal: Journal of the American Society of Nephrology (1994)

Peritoneal dialysis (PD) is dependent on the transport of water and solutes from the blood capillaries within the tissues that surround the peritoneal cavity. Because of their large blood supply and surface area, the viscera have been considered the most important tissues for PD transport. In animals, however, removal of the gastrointestinal tract decreases PD small-solute mass transfer by only 10 to 27%. To investigate the theoretical basis for these observations, a distributed model of peritoneal transport was extended to take into account the transport characteristics of four tissue groups that surround the cavity: the liver, the hollow viscera, the abdominal wall, and the diaphragm. The mass transfer-area coefficient (MTAC) of sucrose for each tissue was calculated from the following: MTAC = ([D(pa)]0.5)A, where D is the effective solute interstitial diffusivity, pa is the solute transcapillary permeability-area per unit tissue volume, and A is the apparent peritoneal surface area of the tissue. Our results for the adult human predict that the MTAC for the liver is comparable to that of all of the other viscera and makes up 43% of the total MTAC for the peritoneal cavity. The predicted MTAC is 4 cm3/min (plasma) or 6 cm3/min (blood), in good agreement with published values. It is concluded that the liver is responsible for a major portion of the small-solute MTAC. This also explains the earlier observations in eviscerated animals whose PD transport was likely preserved by intact livers.
Energy expenditure and physiological responses during indoor rock climbing.
Authors: C M Mermier, R A Robergs, S M McMinn, V H Heyward
Journal: British Journal of Sports Medicine (1997)

To report the physiological responses of indoor rock climbing.Fourteen experienced climbers (nine men, five women) performed three climbing trials on an indoor climbing wall. Subjects performed three trials of increasing difficulty: (a) an easy 90 degrees vertical wall, (b) a moderately difficult negatively angled wall (106 degrees), and (c) a difficult horizontal overhang (151 degrees). At least 15 minutes separated each trial. Expired air was collected in a Douglas bag after four minutes of climbing and heart rate (HR) was recorded continuously using a telemetry unit. Arterialised blood samples were obtained from a hyperaemised ear lobe at rest and one or two minutes after each trial for measurement of blood lactate.Significant differences were found between trials for HR, lactate, oxygen consumption (VO2), and energy expenditure, but not for respiratory exchange ratio. Analysis of the HR and VO2 responses indicated that rock climbing does not elicit the traditional linear HR-VO2 relationship characteristic of treadmill and cycle ergometry exercise. During the three trials, HR increased to 74-85% of predicted maximal values and energy expenditure was similar to that reported for running at a moderate pace (8-11 minutes per mile).These data indicate that indoor rock climbing is a good activity to increase cardiorespiratory fitness and muscular endurance. In addition, the traditional HR-VO2 relationship should not be used in the analysis of this sport, or for prescribing exercise intensity for climbing.
Overexpression of Matrix Metalloproteinase-1 and -9 mRNA Is Associated with Progression of Oral Dysplasia to Cancer
Authors: Richard C. K. Jordan, Maricris Macabeo-Ong, Caroline H. Shiboski, Nusi Dekker, David G. Ginzinger, David T. W. Wong, Brian L. Schmidt
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Although an important risk factor for oral cancer is the presence of epithelial dysplasia, many lesions will not progress to malignancy. Matrix metalloproteinases (MMPs) are zinc-dependent proteinases capable of digesting various structural components of the extracellular matrix. Because MMPs are frequently overexpressed in oral squamous cell carcinoma (SCC), we hypothesized that they are also overexpressed in oral dysplasias; we also hypothesized that those dysplasias that progress to oral cancer express higher levels of MMPs than those lesions that do not progress. Experimental Design: In this retrospective study, we examined changes in MMP-1, -2, and -9 mRNA expression using quantitative TaqMan reverse transcription-polymerase chain reaction in 34 routinely processed oral dysplasias and 15 SCCs obtained from 34 patients. After several years of close follow-up, 19 dysplasias progressed to oral SCC and 15 did not. Results: Overall, MMP-1 mRNA was overexpressed (&amp;gt;2-fold) in 24 of 34 (71%) dysplasias and 13 of 15 (87%) oral SCCs. MMP-2 overexpression was seen in 11 of 34 (32%) dysplasias and 7 of 15 (47%) cancers; for MMP-9, overexpression was identified in 29 of 34 (85%) dysplasias and 15 of 15 (100%) cancers. MMP-1 and -9 levels were significantly higher in the SCCs compared with all oral dysplasias (P = 0.004 and P = 0.01, respectively). MMP-1 and -9 mRNA levels were significantly higher in the oral dysplasias that progressed to oral cancer compared with those that did not (P = 0.04 and P = 0.002, respectively). Conclusions: Levels of MMP-1 and -9 mRNA may be markers of malignant transformation of oral dysplasia to oral cancer.
Raben Lecture 1980: A Tale of Stature*
Authors: HENRY G. FRIESEN
Journal: Endocrine Reviews (1980)

WHEN Dr. Utiger called to invite me to give this lecture, we agreed that it would be acceptable to review some highlights of progress in the field of GH research. By choosing the title “A Tale of Stature,” discretion, if not modesty, dictates that I make only sparing reference to our own work. The choice of title also allows me artistic license to make some interpretive comments. Maury Raben of course is best known for his isolation of hGH and his demonstration that it is an effective therapeutic agent in the treatment of hypopituitary dwarfism. In addition, he performed some important studies on its mechanism of action. But few among you, I suspect, know about some of his other achievements. He studied the mechanism of action of antithyroid drugs in association with Ted Astwood. He developed the first liquid scintillation counter and, had he chosen to patent the process and follow through on it, he might have gained considerable fortune, but that simply was not his style. In his later years as Director of Cardiovascular Research at the New England Center Hospital in Boston he continued to make important contributions in the field. Many fellows who were with him over the years have now, in their own right, become luminaries in the academic world and continue to make important scholarly contributions in endocrinology and metabolism and cardiac research.
Kraken: ultrafast metagenomic sequence classification using exact alignments
Authors: Derrick E Wood, Steven L Salzberg
Journal: Genome biology (2014)

Abstract Kraken is an ultrafast and highly accurate program for assigning taxonomic labels to metagenomic DNA sequences. Previous programs designed for this task have been relatively slow and computationally expensive, forcing researchers to use faster abundance estimation programs, which only classify small subsets of metagenomic data. Using exact alignment of k -mers, Kraken achieves classification accuracy comparable to the fastest BLAST program. In its fastest mode, Kraken classifies 100 base pair reads at a rate of over 4.1 million reads per minute, 909 times faster than Megablast and 11 times faster than the abundance estimation program MetaPhlAn. Kraken is available at http://ccb.jhu.edu/software/kraken/ .
Education, Income, and Incident Heart Failure in Post-Menopausal Women
Authors: Rashmee U. Shah, Marilyn A. Winkleby, Linda Van Horn, Lawrence S. Phillips, Charles B. Eaton, Lisa W. Martin, Milagros C. Rosal, JoAnn E. Manson, Hongyan Ning, Donald M. Lloyd-Jones, Liviu Klein
Journal: Journal of the American College of Cardiology (2011)
Insights into female sperm storage from the spermathecal fluid proteome of the honeybee Apis mellifera
Authors: Boris Baer, Holger Eubel, Nicolas L Taylor, Nicholas O'Toole, A Harvey Millar
Journal: Genome biology (2009)

Female animals are often able to store sperm inside their body--in some species even for several decades. The molecular basis of how females keep non-own cells alive is largely unknown, but since sperm cells are reported to be transcriptionally silenced and, therefore, limited in their ability to maintain their own function, it is likely that females actively participate in sperm maintenance. Because female contributions are likely to be of central importance for sperm survival, molecular insights into the process offer opportunities to observe mechanisms through which females manipulate sperm.We used the honeybee, Apis mellifera, in which queens are highly polyandrous and able to maintain sperm viable for several years. We identified over a hundred proteins representing the major constituents of the spermathecal fluid, which females contribute to sperm in storage. We found that the gel profile of proteins from spermathecal fluid is very similar to the secretions of the spermathecal gland and concluded that the spermathecal glands are the main contributors to the spermathecal fluid proteome. A detailed analysis of the spermathecal fluid proteins indicate that they fall into a range of different functional groups, most notably enzymes of energy metabolism and antioxidant defense. A metabolic network analysis comparing the proteins detected in seminal fluid and spermathecal fluid showed a more integrated network is present in the spermathecal fluid that could facilitate long-term storage of sperm.We present a large-scale identification of proteins in the spermathecal fluid of honeybee queens and provide insights into the molecular regulation of female sperm storage.
Sequence and structural analysis of BTB domain proteins
Authors: Peter J Stogios, Gregory S Downs, Jimmy JS Jauhal, Sukhjeen K Nandra, Gilbert G Privé
Journal: Genome biology (2005)

Abstract Background The BTB domain (also known as the POZ domain) is a versatile protein-protein interaction motif that participates in a wide range of cellular functions, including transcriptional regulation, cytoskeleton dynamics, ion channel assembly and gating, and targeting proteins for ubiquitination. Several BTB domain structures have been experimentally determined, revealing a highly conserved core structure. Results We surveyed the protein architecture, genomic distribution and sequence conservation of BTB domain proteins in 17 fully sequenced eukaryotes. The BTB domain is typically found as a single copy in proteins that contain only one or two other types of domain, and this defines the BTB-zinc finger (BTB-ZF), BTB-BACK-kelch (BBK), voltage-gated potassium channel T1 (T1-Kv), MATH-BTB, BTB-NPH3 and BTB-BACK-PHR (BBP) families of proteins, among others. In contrast, the Skp1 and ElonginC proteins consist almost exclusively of the core BTB fold. There are numerous lineage-specific expansions of BTB proteins, as seen by the relatively large number of BTB-ZF and BBK proteins in vertebrates, MATH-BTB proteins in Caenorhabditis elegans , and BTB-NPH3 proteins in Arabidopsis thaliana . Using the structural homology between Skp1 and the PLZF BTB homodimer, we present a model of a BTB-Cul3 SCF-like E3 ubiquitin ligase complex that shows that the BTB dimer or the T1 tetramer is compatible in this complex. Conclusion Despite widely divergent sequences, the BTB fold is structurally well conserved. The fold has adapted to several different modes of self-association and interactions with non-BTB proteins.
A 12-month prospective cohort study of injury in international rowers
Authors: F Wilson, C Gissane, J Gormley, C Simms
Journal: British Journal of Sports Medicine (2008)

In this study, the injury incidence and association with type and volume of training in international rowers were described.A prospective cohort design was used over a 12-month period.20 international rowers who were competing as part of the Irish Amateur Rowing Union squad system.The rowers were interviewed monthly, and data were collected regarding their training and competition exposure as well as their injury experience.A mean injury rate of 3.67 per 1000 exposure hours was reported with a total of 44 injuries reported in a 12-month period. The mean number of injuries sustained per athlete was 2.2 (1.24) over the 12-month period. The area where the greatest number of injuries were reported was the lumbar spine (31.82% of total injuries, 95% CI 20 to 50) (fig 2) followed by the knee (15.91% of total injuries, 95% CI 10 to 30) and the cervical spine (11.36% of total injuries, 95% CI 5 to 24). Half of the injuries (22 injuries, 50% of total reported injuries) were to the spine (chi(2) = 30.8, df = 9, p = 0.0003). Ergometer training load was the most significantly associated with injury risk (r = 0.68, p = 0.01).International rowers are at higher risk of injury than most non-contact sports and some contact sports. The high risk of lumbar spine injury and the significant association of high volume of ergometer training merit further research to reduce time and competition lost to injury.
Full Disclosure and the Funding of Biomedical Research
Authors: Robert S. Schwartz, Gregory D. Curfman, Stephen Morrissey, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2008)

Clinical studies have become very expensive to conduct, and multiple sources of funding often support a single study. Biomedical journals routinely disclose all sources of funding of the research they publish; this has been standard practice at the Journal for many years. As funding mechanisms grow increasingly complex, however, it has become ever more challenging for editors to ensure the complete reporting of all sources of financial support.Why is this important? Although the science in a submitted manuscript should be judged on its merits, one cannot fully appreciate a study's meaning without acknowledging the subtle biases in design and . . .