tbuckley/cabot-search huggingface dataset:
The HER-2-Targeting Antibodies Trastuzumab and Pertuzumab Synergistically Inhibit the Survival of Breast Cancer Cells
Authors: Rita Nahta, Mien-Chie Hung, Francisco J. Esteva
Journal: Cancer Research (2004)

Abstract Trastuzumab (herceptin) and pertuzumab (Omnitarg, 2C4) are recombinant humanized monoclonal antibodies that target different extracellular regions of the HER-2 tyrosine kinase receptor. We explored combination effects of these agents in the HER-2-overexpressing BT474 breast cancer cell line. Trastuzumab and 2C4 synergistically inhibited the survival of BT474 cells, in part, because of increased apoptosis. Trastuzumab increased 2C4-mediated disruption of HER-2 dimerization with the epidermal growth factor receptor and HER-3. Combination drug treatment reduced levels of total and phosphorylated HER-2 protein and blocked receptor signaling through Akt but did not affect mitogen-activated protein kinase. These results suggest that combining HER-2-targeting agents may be a more effective therapeutic strategy in breast cancer rather than treating with a single HER-2 monoclonal antibody.
Gastric intramural pH in mechanically ventilated patients.
Authors: Z Mohsenifar, J Collier, S K Koerner
Journal: Thorax (1996)

BACKGROUND: The hypothesis that gastric intramural pH (pHi) is predictive of outcome in haemodynamically stable, mechanically ventilated patients was tested in 25 patients on assisted mechanical ventilation for respiratory failure. METHODS: Simultaneous samples of arterial blood and gastric juice were obtained from patients on assist control, synchronised intermittent and pressure control ventilation during the first 48 hours of mechanical ventilation. Gastric pHi was calculated from the equation: pHi= 6.1 + log HCO3/(gastric PCO2 X 0.03). The outcome was survival or death due to respiratory or circulatory failure within 45 days of admission. RESULTS: Gastric pHi proved to be a better predictor of outcome than all presently utilised parameters. Although all patients included in this study were haemodynamically stable and were similar for all laboratory indices, the only variable capable of accurately predicting outcome was gastric pHi. Patients with a normal arterial pH but a gastric intramural pH of less than 7.25 had an observed mortality of 66%. Standard severity of illness scores grossly underestimated mortality rates. The sensitivity and specificity of a gastric pHi value of less than 7.25 in predicting death were 86% and 83%, respectively. A receiver operator curve for all variables exaggerates the superiority of gastric pHi as a predictor of outcome. CONCLUSION: Low gastric pHi, a marker of gastrointestinal ischaemia, may occur in the presence of normal haemodynamics and may be used to predict severity of illness and mortality accurately.
Human connexin40 gap junction channels are modulated by cAMP
Authors: H van Rijen
Journal: Cardiovascular Research (2000)

Objective: Gap junction channels provide for direct electrical coupling between cells, and play an important role in homeostasis and electrical coupling. One of the proteins that form gap junctions, Connexin40 (Cx40), shows restricted expression in the body, and is found in blood vessels and in the atrium and conduction system of the heart. We have investigated whether gap junction channels formed of Cx40 are modulated by protein-kinase-A-mediated phosphorylation. Methods: A communication-deficient human hepatoma cell line (SKHep1) was stably transfected with human Cx40 cDNA and the properties of Cx40 gap junctions channels and their modulation by cAMP were analyzed using immunocytochemistry, Western blotting, dual patch clamp, and dye coupling. Results: Administration of 1 mM 8-Br-cAMP resulted in a mobility shift of Cx40 protein on western blot and increased macroscopic gap junctional conductance between cell pairs by 46.2±12.0% (mean±S.E.M., n=8). Under control conditions, single channel experiments revealed three single channel conductances around 30, 80 and 120 pS. When cAMP was added, channel conductances of 46 and 120 pS were observed. In monolayers, cAMP also increased the permeability of Cx40 gap junction channels for Lucifer Yellow by 58%. Conclusions: Macroscopic conductance and permeability of Cx40 gap junctions is strongly increased by cAMP and may play a role in the regulation of intercellular communication in the heart and vasculature.
Glycemic Variability Is Associated With Quality of Life and Treatment Satisfaction in Patients With Type 1 Diabetes
Authors: Shiho Ayano-Takahara, Kaori Ikeda, Shimpei Fujimoto, Akihiro Hamasaki, Shin-ichi Harashima, Kentaro Toyoda, Yoshihito Fujita, Kazuaki Nagashima, Daisuke Tanaka, Nobuya Inagaki
Journal: Diabetes Care (2014)

Patients with type 1 diabetes have greater glycemic variability than that in patients with type 2 diabetes. However, neither glucose variability nor hypoglycemia is detected precisely by HbA1c. This study investigated whether glycemic variability assessed by continuous glucose monitoring influences quality of life (QOL) and treatment satisfaction in patients with type 1 diabetes.

The study was conducted in Kyoto University Hospital between September 2011 and June 2012. The study protocol was approved by the institutional review board (UMIN Clinical Trials Registry UMI05833). Twenty-eight patients with type 1 diabetes aged ≥18 years were included in analyses (age, 45.9 ± 14.5 [mean ± SD] years; diabetes duration, 15.0 ± 8.2 years; 57% female; 21% using insulin pump; HbA1c, 8.1 ± 1.2% [64.5 ± 13.0 mmol/mol]). Glycemic variability in everyday life was assessed for a 72-h period using the CGMS System Gold continuous glucose …
Fiber and Diabetes
Authors: James W Anderson, Wendy R Midgley, Betty Wedman
Journal: Diabetes Care (1979)

Plant fibers have important influences on gastrointestinal physiology and the absorption of many nutrients. Certain fibers delay the absorption of carbohydrates and result in less postprandial hyperglycemia. Because the intake of plant fibers lowers plasma glucose concentrations and decreases glycosuria, high-fiber foods may be useful in the management of diabetes mellitus. Consumption of selected fibers and fiber-rich foods lowers serum cholesterol values and may lower triglyceride concentrations. Plant fiber intake may lead to mineral depletion or vitamin deficiency, but this has not been observed in several long-term studies. Further work is required to delineate the therapeutic utility of plant fibers in the diet of persons with diabetes and to assess the undesirable effects of fiber intake. In our opinion, persons with diabetes who are eating very low-fiber diets would benefit from an increase in plant fiber intake from whole grains, legumes, and vegetables.
Diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with alcoholic liver disease
Authors: Sylvie Naveau, Guillaume Gaudé, Amani Asnacios, Hélène Agostini, Annie Abella, Nadège Barri‐Ova, Barbara Dauvois, Sophie Prévot, Yen Ngo, Mona Munteanu, Axel Balian, Micheline Njiké‐Nakseu, Gabriel Perlemuter, Thierry Poynard
Journal: Hepatology (2008)

FibroTest has been validated as a biomarker of fibrosis in patients with chronic viral hepatitis, with a similar prognostic value as biopsy. The aim of the study was to compare the diagnostic and prognostic values of FibroTest versus the recently patented biomarkers, FibrometerA, and Hepascore. A total of 218 consecutive patients with ALD and available liver biopsy examination were included. Biomarkers were compared using univariate area under the ROC curves (AUROC) and multivariate analysis (logistic regression and Cox). The median follow-up was 8.2 years. Eighty-five patients died, including 42 deaths related to liver complications. The diagnostic values of FibrometerA and Hepascore did not differ from that of FibroTest for advanced fibrosis (all AUROC = 0.83 +/- 0.03) and cirrhosis (FibroTest and FibrometerA = 0.94 +/- 0.02, Hepascore = 0.92 +/- 0.02), and were significantly greater than those of nonpatented biomarkers (APRI, Forns, FIB4; P < 0.01). In multivariate analysis the most significant was FibroTest (P = 0.001), without independent diagnostic value for FibrometerA (P = 0.19), and Hepascore (P = 0.40). The prognostic values of FibroTest (AUROC for survival or non liver disease-related death = 0.79 +/- 0.04), FibrometerA (0.80 +/- 0.04), Hepascore (0.78 +/- 0.04), did not differ from that of biopsy fibrosis staging (0.77 +/- 0.04). In multivariate analysis the most significant were FibroTest (P = 0.004) and biopsy (P = 0.03), without independent prognostic values for FibrometerA (P = 0.41) and Hepascore (P = 0.28). In patients with alcoholic liver disease, FibrometerA and Hepascore did not improve the diagnostic and prognostic values of FibroTest.
Comprehensive Analysis of Simple Sequence Repeats in Pre-miRNAs
Authors: Ming Chen, Zhongyang Tan, Guangming Zeng, Jun Peng
Journal: Molecular Biology and Evolution (2010)

Simple sequence repeats (SSRs) are tandem repeat units of 1-6 bp that are identified in various complete sequences. However, the distribution, nature, and origination of SSRs in pre-miRNAs, which are characteristic stem-loop sequences and are finally processed into ∼22 nt functional miRNAs contributing to regulate several biological processes, are still not well studied. The availability of large numbers of pre-miRNAs makes it possible to analyze and compare the occurrences of SSRs, the relative count of SSRs, or the longest SSRs in pre-miRNAs. In this study, we analyzed SSRs in 8,619 pre-miRNAs from 87 species, including Arthropoda, Nematoda, Platyhelminthes, Urochordata, Vertebrata, Mycetozoa, Protistae, Viridiplantae, and Viruses. We find that SSRs widely exist in the pre-miRNAs analyzed. Our analysis shows that mononucleotide repeats are the most abundant repeats, followed by dinucleotide repeats, whereas tri-, tetra-, penta-, and hexanucleotide repeats rarely occurred in pre-miRNAs. The number of SSRs per pre-miRNA on average ranges from 4.1 for viruses to 13.5 for Mycetozoa. Our results confirm that the number of repeats correlates inversely to the length of repeats. Generally, in each taxonomic group, the occurrence and relative count of SSRs decrease with the increase of repeat unit. SSRs do not exhibit obvious preference for special location in pre-miRNAs. The repeats in pre-miRNAs are complementary to repeats in coding or noncoding regions of genomes, and no significant difference is observed between these two classes with respect to the occurrence of repeats. These data on SSRs may become a useful resource of pre-miRNAs, and their possible functions are discussed.
The anti-inflammatory effects of macrolides
Authors: D. Wales, M. Woodhead
Journal: Thorax (1999)

Erythromycin and its fourteen-member macrolide analogues have attracted attention for their efficacy in bronchial asthma.However, their mechanisms of action remain unclear.We evaluated the effects of the macrolide antibiotics on endothelin-1 (ET-1) expression in normal and transformed human bronchial epithelial cells, one of the sources of this potent bronchoconstrictor important in the pathogenesis of asthma.Human bronchial epithelial cells were obtained from the resected bronchi, and the effect of several antimicrobial and antiasthmatic drugs on the production and messenger ribonucleic acid (mRNA) levels of ET-1 was evaluated.Bronchoepithelial cells were also isolated from the mucosa of asthmatic patients under fibreoptic bronchoscopy, and the modulating effects of the drug were studied.Erythromycin and clarithromycin uniquely suppressed mRNA levels as well as the release of ET-1 at therapeutic and non-cytotoxic concentrations (percentage inhibition of ET-1 protein release: 26.4±5.22%and 31.2±7.45%,respectively, at 10 -6 M).Furthermore, erythromycin and clarithromycin inhibited ET-1 expression in bronchoepithelial cells from patients with chronic, stable asthma.A glucocorticosteroid, dexamethasone, also inhibited ET-1 expression.In contrast, theophylline, salbutamol and FK506 had no effect on ET-1 production.Our findings demonstrated that these fourteen-member macrolide antibiotics had an inhibitory effect on endothelin-1 expression in human bronchial epithelial cells.Moreover, this new mode of action may have some relevance to their clinical efficacy in bronchial asthma.
Remarks on the Phenomena of Locomotor Ataxy: With an Appendix Relative to Discussion Thereon
Authors: T. C. Allbutt
Journal: BMJ (1869)

AT meetings like these of the British Medical Association, I think we should take the opportunity of bringing questions forward which will lead to a discussion of well-known difficulties.We discuss those sub- jects best at public meetings, of which we already know the main facts, and we can deal better with new interpretations of things already veri- fied than with new statements which require verification.Instead, therefore, of laying before you, as I had thought of doing, some observations on the use of the ophthalmoscope in railway accidents, I have determined to ask you to consider whether we rightly interpret those phenomena which are familiar to us in the group called Locomotor Ataxy.The group of facts which we designate under this name, and under other similar names, are known to us all, but I venture to think that their interpretation differs somewhat from that which is usually put for- ward.I will first enumerate the symptoms of the disease, and I will take the liberty of enumerating them in the words of Dr. Radcliffe in his recent article in Reynolds's System of Medicine.There is "a peculiar gait -a gait precipitate and staggering, the legs startinig hither and thither in a very disorderly manner, and the heels coming down with a stamp at each step.No true paralysis in the lower extremities or elsewhere.Characteristic neuralgic pains, erratic, paroxysmal in the feet and legs chiefly-pains of a boring, thrilling, shooting character like those caused by a sharp electric shock.More or less numbness, in the feet and legs chiefly, in all forms of sensibility, excepting that by which differences of temperature are recognised.Frequent impairment of sight and hearing, one or both.Frequent transitory and permanent strabismus or ptosis, one or both.No very obvious paralysis of the bladder or lower bowel.
Temporal adjustment of the juxtaglomerular apparatus during sustained inhibition of proximal reabsorption
Authors: Scott C. Thomson, Sebastian Bachmann, Magdalena Bostanjoglo, Carolyn A. Ecelbarger, Orjan W. Peterson, Doron Schwartz, Dingjiu Bao, Roland C. Blantz
Journal: Journal of Clinical Investigation (1999)

Tubuloglomerular feedback (TGF) stabilizes nephron function by causing changes in single-nephron GFR (SNGFR) to compensate for changes in late proximal flow (VLP). TGF responds within seconds and reacts over a narrow range of VLP that surrounds normal VLP. To accommodate sustained increases in VLP, TGF must reset around the new flow. We studied TGF resetting by inhibiting proximal reabsorption with benzolamide (BNZ; administered repeatedly over a 24-hour period) in Wistar-Froemter rats. BNZ acutely activates TGF, thereby reducing SNGFR. Micropuncture was performed 6–10 hours after the fourth BNZ dose, when diuresis had subsided. BNZ caused glomerular hyperfiltration, which was prevented with inhibitors of macula densa nitric oxide synthase (NOS). Because of hyperfiltration, BNZ increased VLP and distal flow, but did not affect the basal TGF stimulus (early distal salt concentration). BNZ slightly blunted normalized maximum TGF response and the basal state of TGF activation. BNZ sensitized SNGFR to reduction by S-methyl-thiocitrulline (SMTC) and caused the maximum TGF response to be strengthened by SMTC. Sensitization to type I NOS (NOS-I) blockers correlated with increased macula densa NOS-I immunoreactivity. Tubular transport measurements confirmed that BNZ affected TGF within the juxtaglomerular apparatus. During reduced proximal reabsorption, TGF resets to accommodate increased flow and SNGFR through a mechanism involving macula densa NOS.
Group A Streptococci, Mycoplasmas, and Viruses Associated With Acute Pharyngitis
Authors: W. Paul Glezen
Journal: JAMA (1967)

Methods for identification of bacteria, viruses, and mycoplasmas were used to study pharyngitis in patients from a pediatric practice. Etiologic agents were recovered from 50% of 715 cultures from patients with pharyngitis and from 22% of 206 cultures from asymptomatic household contracts. Pharyngitis was diagnosed most often in children ages 6 through 8 years, and over one half of these illnesses were associated with group A streptococcus infections. Viruses were the most important cause of pharyngitis in infants, and Mycoplasma pneumoniae was associated with pharyngitis in early adolescence. Disease produced by viruses or M pneumoniae could not be distinguished from classical streptococcal pharyngitis. Mycoplasma hominis, which has produced exudative pharyngitis in adult volunteers, was not recovered from persons in this investigation; however, in other studies performed concurrently, M hominis was isolated from 0.5% of subjects including three adults with pharyngitis.
The synthesis of the <sup>G</sup>γ and <sup>A</sup>γ chains of human fetal hemoglobin in erythroid colonies cultured from peripheral blood BFUe's of normal adults and newborn and of subjects with an <sup>A</sup>γ or a <sup>G</sup>γ chain abnormal fetal hemoglobin
Authors: T. H. J. Huisman, A. L. Reese, M. E. Gravely, H. Harris, J. B. Wilson
Journal: American Journal of Hematology (1980)

Abstract Peripheral blood mononuclear cells from normal adults, normal newborn infants, and from newborn and adult subjects with one of three γ chain variants ( G γF‐Malta I, G γF‐Port Royal, A γF‐Hull) were cultured in vitro with erythropoietin. The 35 S‐methionine‐labelled hemoglobin from 13‐ to 15‐day‐old BFUe‐derived colonies was studied by chromatography on columns of DEAE‐cellulose and the quantities of Hbs A 2 , F x , and F 0 determined. The percentages of G γ and A γ chains in isolated Hb F x and Hb F 0 were determined using high‐performance liquid chromatography (HPLC) of the tryptic peptides of these proteins. Calculation of these percentages was based on the total activities of the G γT‐15 and A γT‐15 peptides which contain one ( 35 S‐labelled) methionyl residue each and can be separated by the HPLC procedure. The data show an increased synthesis of Hb F in the „adult”︁ colonies and a decreased synthesis in the „newborn”︁ colonies. The G γ to A γ ratio of the Hb F from adult colonies varied greatly. The percentages of G γ and A γ chains in the Hb F from adult colonies correlated with the percentages in the Hb F isolated from the Hb F of circulating red blood cells. The G γ to A γ ratio in the Hb F from newborn colonies was high as in the Hb F from cord blood samples. G γ and A γ chain abnormal Hb F variants were readily detectable in colonies from both adults and newborn. The G γ to A γ ratio in the Hb F of colonies of adult Hb F‐Malta I and Hb F‐Hull heterozygotes approached 1, but that of adult Hb F‐Port Royal heterozygotes remained about as high as in colonies from newborn heterozygotes. The percent Hb F‐Port Royal in the Hb F of adult colonies was twice that in the Hb F of newborn colonies. These results are discussed in the light of information from recent detailed studies of genomic DNA assuming controlling functions for the segments of DNA that are interspersed between the various structural genes.
Role of the Coagulation/Fibrinolysis System in Fibrin-Associated Glomerular Injury
Authors: Alexandre Hertig, Eric Rondeau
Journal: Journal of the American Society of Nephrology (2004)

In the past decade, numerous experimental studies of genetically engineered mice have confirmed the involvement of the coagulation/fibrinolysis system during glomerular inflammation and repair, revealing many unexpected biologic effects far beyond fibrin formation and clearance. Resident glomerular cells and macrophages seem to act in concert to ensure the long-term consolidation of local injury and progression toward glomerulosclerosis. These recent advances will probably pave the way to a new therapeutic approach to renal diseases. However, the balance governing glomerular permeability is very delicate, and many issues will have to be dealt with before targeting this system.
Enhancing Skin Cancer Screening Through Behavioral Intervention
Authors: Carolyn J. Heckman
Journal: JAMA Dermatology (2014)

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Risk Indicators Predictive for Severe Hypoglycemia During the First Trimester of Type 1 Diabetic Pregnancy
Authors: Inge M. Evers, Edith W.M.T. ter Braak, Harold W. de Valk, Bertine van der Schoot, Nancy Janssen, Gerard H.A. Visser
Journal: Diabetes Care (2002)

OBJECTIVES—To investigate the frequency of severe hypoglycemia (SH) and hypoglycemic coma during the first trimester of type 1 diabetic pregnancy and in the 4 months before gestation and to identify risk indicators predicting first trimester SH in a nonselected nationwide cohort of pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS—We conducted a longitudinal cohort survey in 278 pregnant type 1 diabetic women using questionnaires at inclusion and at 17 weeks of gestation, addressing the frequencies of SH (i.e., external help required) and hypoglycemic coma, general characteristics, hypoglycemia awareness, blood glucose symptom threshold, and the Hypoglycemia Fear Survey. RESULTS—The occurrence of SH (including hypoglycemic coma) rose from 0.9 ±2.4 episodes per 4 months before gestation to 2.6 ±6.3 episodes during the first trimester (P &amp;lt; 0.001), including an increase in episodes of coma from 0.3 ±1.3 to 0.7 ±3.7 (P=0.03). The proportion of women affected by SH rose from 25 to 41% (P &amp;lt; 0.001). First-trimester SH was independently related to a history of SH before gestation (odds ratio [95%CI]: 9.2 [3.9ndash;21.7]), a 10 years’ longer diabetes duration (1.6 [1.0ndash;2.4]), an HbA1c level ≤6.5% (2.5 [1.3ndash;5.0]), and a 0.1 unit/kg higher daily insulin dose (5.4 [1.5ndash;18.9]), adjusted for a decreased symptom threshold. CONCLUSIONS—In type 1 diabetic pregnancy, the risk of SH is increased already before pregnancy and rises further during the first trimester. A history of SH before gestation, longer duration of diabetes, an HbA1c level ≤6.5%, and a higher total daily insulin dose were risk indicators predictive for SH during the first trimester. Further research should aim to elucidate how the benefits of strict glycemic control balance with the markedly increased risk of SH early in pregnancy.