tbuckley/cabot-search huggingface dataset:
CD80 (B7-1) and CD86 (B7-2) antigens on house dust mite–specific T cells in atopic disease function through T-T cell interactions☆☆☆
Authors: Michihiro Nakada, Kazunori Nishizaki, Tadashi Yoshino, Mitsuhiro Okano, Takayoshi Yamamoto, Yu Masuda, Nobuo Ohta, Tadaatsu Akagi
Journal: Journal of Allergy and Clinical Immunology (1999)
Impact of Solute Intake on Urine Flow and Water Excretion
Authors: Tomas Berl
Journal: Journal of the American Society of Nephrology (2008)

It is classically taught that when renal function is normal and the secretion of antidiuretic hormone (arginine vasopressin) is fully suppressed, the human kidney has the capacity to excrete large volumes of dilute urine, allowing for a broad range of water intake. This flexibility protects against the development of hyponatremia even in the face of water intake that can approach 20 L/d. What is not as widely recognized is the impact that alterations in solute intake, and therefore excretion, have on this process. As will be illustrated here, a decrement in solute intake markedly reduces the above-mentioned flexibility and puts the individual at risk for the unexpected development of hyponatremia. In contrast, an increment in solute intake can be used therapeutically to treat this electrolyte disorder and allow those prone to it to liberalize their water intake.
Gene expression of interleukin 18 in unstimulated peripheral blood mononuclear cells of patients with alcoholic cirrhosis
Authors: C Hanck
Journal: Gut (2001)

<h3>BACKGROUND</h3> Most patients with alcohol induced cirrhosis (AC) and chronic endotoxinaemia are not suffering from clinically evident systemic inflammatory reactions. This may be due to altered gene expression of cytokines, possibly related to endotoxin (for example, tolerance and sensitisation). Interleukin 18 (IL-18; interleukin γ inducing factor) modulates local cytokine production in response to endotoxin (lipopolysaccharide (LPS)). <h3>AIM</h3> To investigate the systemic immune response of patients with AC and to see if unstimulated peripheral blood mononuclear cells (PBMC) from patients with AC are activated and contribute to gene expression of IL-18. <h3>METHODS</h3> Plasma levels of endotoxin (LPS) and serum levels of IL-18 were measured by enzyme linked immunoassay and the amoebocyte lysate test in 74 abstinent patients with different stages of AC (Child-Pugh stage A, n=18; B, n=22; C, n=34) and compared with healthy controls (n=43). Gene expression of IL-18 was assessed by semiquantitative reverse transcription-polymerase chain reaction in freshly isolated unstimulated PBMC of a subgroup of 14 patients with AC compared with five healthy controls. <h3>RESULTS</h3> Gene expression of IL-18 specific mRNA in unstimulated PBMC was significantly enhanced in patients with advanced AC (Child-Pugh stage C) and correlated with plasma LPS and serum CD14 levels (Spearman rank correlation factors <i>r</i>=0.76 and<i>r</i>=0.72). Serum concentrations of IL-18 were also elevated compared with healthy controls (p&lt;0.001) but correlation with serum levels of CD14 and plasma levels of LPS was much weaker compared with mRNA data (Spearman rank correlation factors<i>r</i>=0.47 and<i>r</i>=0.26). <h3>CONCLUSIONS</h3> Our in vivo data suggest a presensitisation of "unstimulated" PBMC in the circulation of patients with AC by endotoxin. The term "unstimulated" may be inadequate in patients with AC. Further investigations are needed to define the exact mechanisms and localisation of sensitisation of PBMC in vivo.
Influence of Pituitary, Thyroid, and Adrenal Hormones on Norepinephrine Turnover and Metabolismin the Rat Heart
Authors: LEWIS LANDSBERG, JULIUS AXELROD
Journal: Circulation Research (1968)

Norepinephrine turnover was estimated in the rat heart from the rate of release of tracer 3 H-norepinephrine and the depletion of endogenous norepinephrine after inhibition of synthesis. Cardiac norepinephrine turnover was markedly increased in chronically hypophysectomized rats. Thyroidectomy and adrenalectomy were also associated with increased cardiac norepinephrine turnover, whereas ovariectomy was not. Chronic treatment of hypophysectomized rats with thyroxine and ACTH restored the turnover to normal, the replacement of thyroxine being quantitatively more significant. Cardiac atrophy and decreased blood pressure occurred concomitantly with increased norepinephrine turnover in the hypophysectomized rat and were restored to normal with thyroid treatment. Ganglionic blockade of the hypophysectomized rat also restored the turnover toward normal. The metabolites of 3 H-norepinephrine were shifted with a decrease in O-methylated metabolites and an increase in deaminated products. This evidence suggests that thyroid deficiency and, to a lesser extent, adrenal deficiency are associated with an increase in cardiac norepinephrine turnover mediated by an increase in sympathetic nervous activity. The role of the increased turnover in relation to the hormonal deficiencies is discussed.
MEK-ERK1/2-Dependent FLNA Overexpression Promotes Abnormal Dendritic Patterning in Tuberous Sclerosis Independent of mTOR
Authors: Longbo Zhang, Christopher M. Bartley, Xuan Gong, Lawrence S. Hsieh, Tiffany V. Lin, David M. Feliciano, Angélique Bordey
Journal: Neuron (2014)

Abnormal dendritic complexity is a shared feature of many neurodevelopmental disorders associated with neurological defects. Here, we found that the actin-crosslinking protein filamin A (FLNA) is overexpressed in tuberous sclerosis complex (TSC) mice, a PI3K-mTOR model of neurodevelopmental disease that is associated with abnormal dendritic complexity. Both under- and overexpression of FLNA in wild-type neurons led to more complex dendritic arbors in vivo, suggesting that an optimal level of FLNA expression is required for normal dendritogenesis. In Tsc1 null neurons, knocking down FLNA in vivo prevented dendritic abnormalities. Surprisingly, FLNA overexpression in Tsc1 null neurons was dependent on MEK1/2 but not mTOR activity, despite both pathways being hyperactive. In addition, increasing MEK-ERK1/2 activity led to dendritic abnormalities via FLNA, and decreasing MEK-ERK1/2 signaling in Tsc1 null neurons rescued dendritic defects. These data demonstrate that altered FLNA expression increases dendritic complexity and contributes to pathologic dendritic patterning in TSC in an mTOR-independent, ERK1/2-dependent manner.
Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice
Authors: Yasuhiko Yamamoto, Ichiro Kato, Toshio Doi, Hideto Yonekura, Seiji Ohashi, Masayoshi Takeuchi, Takuo Watanabe, Sho-ichi Yamagishi, Shigeru Sakurai, Shin Takasawa, Hiroshi Okamoto, Hiroshi Yamamoto
Journal: Journal of Clinical Investigation (2001)

Vascular complications arising from multiple environmental and genetic factors are responsible for many of the disabilities and short life expectancy associated with diabetes mellitus. Here we provide the first direct in vivo evidence that interactions between advanced glycation end products (AGEs; nonenzymatically glycosylated protein derivatives formed during prolonged hyperglycemic exposure) and their receptor, RAGE, lead to diabetic vascular derangement. We created transgenic mice that overexpress human RAGE in vascular cells and crossbred them with another transgenic line that develops insulin-dependent diabetes shortly after birth. The resultant double transgenic mice exhibited increased hemoglobin A1c and serum AGE levels, as did the diabetic controls. The double transgenic mice demonstrated enlargement of the kidney, glomerular hypertrophy, increased albuminuria, mesangial expansion, advanced glomerulosclerosis, and increased serum creatinine compared with diabetic littermates lacking the RAGE transgene. To our knowledge, the development of this double transgenic mouse provides the first animal model that exhibits the renal changes seen in humans. Furthermore, the phenotypes of advanced diabetic nephropathy were prevented by administering an AGE inhibitor, (±)-2-isopropylidenehydrazono-4-oxo-thiazolidin-5-ylacetanilide (OPB-9195), thus establishing the AGE-RAGE system as a promising target for overcoming this aspect of diabetic pathogenesis.
Exhaled Biomarkers and Gene Expression at Preschool Age Improve Asthma Prediction at 6 Years of Age
Authors: Ester M. M. Klaassen, Kim D. G. van de Kant, Quirijn Jöbsis, Onno C. P. van Schayck, Agnieszka Smolinska, Jan W. Dallinga, Frederik J. van Schooten, Gertjan J. M. den Hartog, Johan C. de Jongste, Ger T. Rijkers, Edward Dompeling
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

A reliable asthma diagnosis is difficult in wheezing preschool children.To assess whether exhaled biomarkers, expression of inflammation genes, and early lung function measurements can improve a reliable asthma prediction in preschool wheezing children.Two hundred two preschool recurrent wheezers (aged 2-4 yr) were prospectively followed up until 6 years of age. At 6 years of age, a diagnosis (asthma or transient wheeze) was based on symptoms, lung function, and asthma medication use. The added predictive value (area under the receiver operating characteristic curve [AUC]) of biomarkers to clinical information (assessed with the Asthma Predictive Index [API]) assessed at preschool age in diagnosing asthma at 6 years of age was determined with a validation set. Biomarkers in exhaled breath condensate, exhaled volatile organic compounds (VOCs), gene expression, and airway resistance were measured.At 6 years of age, 198 children were diagnosed (76 with asthma, 122 with transient wheeze). Information on exhaled VOCs significantly improved asthma prediction (AUC, 89% [increase of 28%]; positive predictive value [PPV]/negative predictive value [NPV], 82/83%), which persisted in the validation set. Information on gene expression of toll-like receptor 4, catalase, and tumor necrosis factor-α significantly improved asthma prediction (AUC, 75% [increase of 17%]; PPV/NPV, 76/73%). This could not be confirmed after validation. Biomarkers in exhaled breath condensate and airway resistance (pre- and post- bronchodilator) did not improve an asthma prediction. The combined model with VOCs, gene expression, and API had an AUC of 95% (PPV/NPV, 90/89%).Adding information on exhaled VOCs and possibly expression of inflammation genes to the API significantly improves an accurate asthma diagnosis in preschool children. Clinical trial registered with www.clinicaltrial.gov (NCT 00422747).
An Uncommon Complication of Nondissected Ascending Aortic Aneurysm
Authors: Enrique Antón, Mariam Echeverría
Journal: Circulation (2005)

A n 86-year-old woman was admitted with a 2-week-long history of increasing dyspnea.She had an ascending thoracic aortic aneurysm (8ϫ9 cm) diagnosed 5 years before.On admission, the patient was in moderate respiratory distress.Her vital signs were blood pressure 130/80, heart rate 72 bpm (irregular), respiration rate 32 rpm, and temperature 36°C.Chest auscultation revealed decreased breath sounds at right base.The ECG showed atrial fibrillation.Basic laboratory data were unremarkable.Chest x-ray findings are shown in Figure 1.The echocardiogram revealed a nonenlarged left ventricle.Thoracocentesis yielded a pleural fluid with characteristics of transsudate.A thoracic CT scan confirmed that aortic aneurysm had been enlarged (9.5ϫ10 cm), extended posteriorly, and severely compressed the right pulmonary
Disease-Specific T-Helper Cell Polarizing Function of Lesional Dendritic Cells in Different Types of Chronic Rhinosinusitis with Nasal Polyps
Authors: Li-Li Shi, Jia Song, Peng Xiong, Ping-Ping Cao, Bo Liao, Jin Ma, Ya-Na Zhang, Ming Zeng, Yang Liu, Heng Wang, Yong-Hua Cui, Shau-Ku Huang, Zheng Liu
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Although eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) exhibit distinct T-helper (Th) responses, the underlying mechanisms remain unclear.To clarify the phenotypes and Th-cell polarizing functions of dendritic cells (DCs) in different types of CRSwNP.DC subsets, their surface phenotypes, and Th-cell subsets were studied by means of immunohistochemistry and flow cytometry. The sorted lesional DCs were activated or cultured with autologous naive CD4(+) T cells, and cytokine production was determined by ELISA. Thymic stromal lymphopoietin and osteopontin expression were detected by means of reverse-transcriptase polymerase chain reaction.Although elevated local Th1 and Th17 cells were noted in both eosinophilic and noneosinophilic CRSwNP, increased Th2 cells were found only in eosinophilic CRSwNP. Increased numbers of myeloid DCs, plasmacytoid DCs, and their activated subsets were found in both types of CRSwNP, but only myeloid DCs and plasmacytoid DCs from eosinophilic CRSwNP demonstrated an up-regulation of OX40 ligand (OX40L) and programmed death ligand 1(PD-L1) expression. Lesional DCs from both types of CRSwNP produced enhanced levels of IL-12, IL-6, and transforming growth factor-β, and induced increased Th1 and Th17 responses; in contrast, only DCs from eosinophilic CRSwNP induced obviously enhanced Th2 responses, when cocultured with naive CD4(+) T cells. Blockade of OX40L and PD-L1 on lesional DCs from eosinophilic CRSwNP suppressed Th2 responses, but promoted Th1 responses in DC-T cell coculture.Distinct subsets of lesional DCs were found in eosinophilic and noneosinophilic CRSwNP, where OX40L/PD-L1(+) lesional DCs in eosinophilic CRSwNP could prime Th2 cells, whereas the low OX40L/PD-L1-expressing lesional DCs in noneosinophilic CRSwNP primarily induced Th1/Th17 cells.
Clinicopathologic Significance and Prognostic Value of Chromosomal Imbalances in Diffuse Large B-Cell Lymphomas
Authors: Sílvia Beà, Lluís Colomo, Armando López-Guillermo, Itziar Salaverria, Xavier Puig, Magda Pinyol, Susana Rives, Emili Montserrat, Elias Campo
Journal: Journal of Clinical Oncology (2004)

Purpose To determine the clinicopathologic significance and prognostic value of chromosomal imbalances in diffuse large B-cell lymphomas (DLBCL). Patients and Methods We have examined 64 tumors at diagnosis using comparative genomic hybridization and real-time quantitative polymerase chain reaction (PCR), single-stranded conformational polymorphism, and DNA sequencing for the analysis of several potential target genes. Results The most recurrent alterations were gains of 18q (20%), Xq (15%), 2p, 7q, and 12p (14%), and losses of 6q and 17p (14%). Frequent high-level DNA amplifications were detected at 2p13-p16 and 18q21 loci. Real-time quantitative PCR detected REL and BCL11A gene amplifications in the nine patients with gains at 2p13-p16 and only in one additional patient with normal chromosome 2. Similarly, the BCL-2 gene was amplified in the 12 tumors with gains of 18q21 but in none of 39 patients with normal 18q profile. p53 gene inactivation was detected in nine of 58 (16%) tumors and was commonly associated with 17p losses. Tumors with 18q gains were significantly associated with a high number of chromosomal imbalances, primary nodal presentation, high serum lactate dehydrogenase levels, high International Prognostic Index, shorter cause-specific survival, and a high risk of relapse. Losses of 17p and p53 gene alterations were associated with an absence of complete response achievement. Conclusion These results suggest that DLBCLs have a characteristic pattern of genomic alterations; 18q gains or amplifications and 17p losses are associated with particular clinicopathological features and aggressive clinical behavior. Additional studies are needed to confirm these observations in larger series of patients.
Serotonin, Bananas, and Diarrhoea
Authors: A. M. Connell, E. N. Rowlands, P. B. Wilcox
Journal: Gut (1960)

From previous studies on serotonin it seemed possible that it might play a major rôle in determining the rhythm of the bowel in man. This hypothesis was tested, with negative results, by observing the effect of giving bananas, a rich natural source of serotonin, to normal subjects and by measuring the excretion of 5-hydroxyindolacetic acid in patients with diarrhoea.
The significance of IgM antibodies to hepatitis B core antigen in hepatitis B carriers and hepatitis B-associated chronic liver disease
Authors: Victor S. Feinman, Lacy R. Overby, Barnet Berris, Kurt Chau, Charles A. Schable, James E. Maynard
Journal: Hepatology (1982)

IgM antibody to hepatitis B core antigen (IgM anti–HBc) was determined in 60 patients whose serum was positive for hepatitis B surface antigen (HBsAg) and 18 patients whose serum was negative for HBsAg, but positive for antibody to hepatitis B core antigen (anti–HBc). Two radioimmunoassays were done utilizing either anti–u antibody to capture IgM or Staphylococcus A protein to separate IgG and IgM. Both methods failed to detect IgM anti–HBc in 30 healthy carriers, 5 HBsAg–positive cirrhotics, 2 patients with HBsAg–positive hepatocellular carcinoma, and 18 HBsAg–negative anti–HBc–positive patients. IgM anti–HBc was present in all 4 patients with acute hepatitis B and in 4 of 8 patients with HBsAg–positive chronic active hepatitis. In patients with chronic active hepatitis, IgM anti–HBc was positive in those with the most intense infiltrate of mononuclear cells on liver biopsy. There was no correlation with the presence of hepatitis B e antigen or anti–HBe. Three of 11 patients with HBsAg–positive chronic persistent hepatitis were intermittently positive by the Staphylococcus A method but all were negative by the u–capture method when a low sensitivity cutoff was employed. The sensitivity of the test can be adjusted at will by the manufacturers and, therefore, introduction of interchangeable controls and standards will enable clinical application of this testing system with meaningful results. Testing for IgM anti–HBc may help the clinician in differentiating healthy HBsAg carriers from patients with HBsAg–positive acute and chronic hepatitis. It is also of value in differentiating patients with acute hepatitis B from HBsAg carriers who develop acute hepatitis of different etiology. Accumulation of more data and correlations with the intensity and nature of the mononuclear infiltrates in chronic hepatitis will increase understanding of the mechanism of switchover from IgM to IgG anti–HBc response and factors favoring chronicity in hepatitis B.
Molecular Mechanisms RegulatinG Th1 Immune Responses
Authors: Susanne J. Szabo, Brandon M. Sullivan, Stanford L. Peng, Laurie H. Glimcher
Journal: Annual Review of Immunology (2003)

The T helper lymphocyte is responsible for orchestrating the appropriate immune response to a wide variety of pathogens. The recognition of the polarized T helper cell subsets Th1 and Th2 has led to an understanding of the role of these cells in coordinating a variety of immune responses, both in responses to pathogens and in autoimmune and allergic disease. Here, we discuss the mechanisms that control lineage commitment to the Th1 phenotype. What has recently emerged is a rich understanding of the cytokines, receptors, signal transduction pathways, and transcription factors involved in Th1 differentiation. Although the picture is still incomplete, the basic pathways leading to Th1 differentiation can now be understood in in vitro and a number of infection and disease models.
Interpregnancy interval and risk of preterm birth and neonatal death: retrospective cohort study
Authors: G. C S Smith
Journal: BMJ (2003)

To determine whether a short interval between pregnancies is an independent risk factor for adverse obstetric outcome.Retrospective cohort study.Scotland.89 143 women having second births in 1992-8 who conceived within five years of their first birth.Intrauterine growth restriction (birth weight less than the 5th centile for gestational age), extremely preterm birth (24-32 weeks), moderately preterm birth (33-36 weeks), and perinatal death.Women whose subsequent interpregnancy interval was less than six months were more likely than other women to have had a first birth complicated by intrauterine growth restriction (odds ratio 1.3, 95% confidence interval 1.1 to 1.5), extremely preterm birth (4.1, 3.2 to 5.3), moderately preterm birth (1.5, 1.3 to 1.7), or perinatal death (24.4, 18.9 to 31.5). They were also shorter, less likely to be married, and more likely to be aged less than 20 years at the time of the second birth, to smoke, and to live in an area of high socioeconomic deprivation. When the outcome of the second birth was analysed in relation to the preceding interpregnancy interval and the analysis confined to women whose first birth was a term live birth (n = 69 055), no significant association occurred (adjusted for age, marital status, height, socioeconomic deprivation, smoking, previous birth weight vigesimal, and previous caesarean delivery) between interpregnancy interval and intrauterine growth restriction or stillbirth. However, a short interpregnancy interval (< 6 months) was an independent risk factor for extremely preterm birth (adjusted odds ratio 2.2, 1.3 to 3.6), moderately preterm birth (1.6, 1.3 to 2.0), and neonatal death unrelated to congenital abnormality (3.6, 1.2 to 10.7). The adjusted attributable fractions for these associations were 6.1%, 3.9%, and 13.8%. The associations were very similar when the analysis was confined to married non-smokers aged 25 and above.A short interpregnancy interval is an independent risk factor for preterm delivery and neonatal death in the second birth.
Speech and gesture are mediated by independent systems
Authors: Anna M. Barrett, Anne L. Foundas, Kenneth M. Heilman
Journal: Behavioral and Brain Sciences (2005)

Arbib suggests that language emerged in direct relation to manual gestural communication, that Broca's area participates in producing and imitating gestures, and that emotional facial expressions contributed to gesture-language coevolution. We discuss functional and structural evidence supporting localization of the neuronal modules controlling limb praxis, speech and language, and emotional communication. Current evidence supports completely independent limb praxis and speech/language systems.
Mesenchymal Stem Cells
Authors: Adam R. Williams, Joshua M. Hare
Journal: Circulation Research (2011)

Mesenchymal stem cells (MSCs) are a prototypical adult stem cell with capacity for self-renewal and differentiation with a broad tissue distribution. Initially described in bone marrow, MSCs have the capacity to differentiate into mesoderm- and nonmesoderm-derived tissues. The endogenous role for MSCs is maintenance of stem cell niches (classically the hematopoietic), and as such, MSCs participate in organ homeostasis, wound healing, and successful aging. From a therapeutic perspective, and facilitated by the ease of preparation and immunologic privilege, MSCs are emerging as an extremely promising therapeutic agent for tissue regeneration. Studies in animal models of myocardial infarction have demonstrated the ability of transplanted MSCs to engraft and differentiate into cardiomyocytes and vasculature cells, recruit endogenous cardiac stem cells, and secrete a wide array of paracrine factors. Together, these properties can be harnessed to both prevent and reverse remodeling in the ischemically injured ventricle. In proof-of-concept and phase I clinical trials, MSC therapy improved left ventricular function, induced reverse remodeling, and decreased scar size. This article reviews the current understanding of MSC biology, mechanism of action in cardiac repair, translational findings, and early clinical trial data of MSC therapy for cardiac disease.