tbuckley/cabot-search huggingface dataset:
Interventions With Adherence-Promoting Components in Pediatric Type 1 Diabetes
Authors: Korey K. Hood, Jennifer M. Rohan, Claire M. Peterson, Dennis Drotar
Journal: Diabetes Care (2010)

To review interventions with adherence-promoting components and document their impact on glycemic control via meta-analysis.Data from 15 studies that met the following criteria were subjected to meta-analysis: 1) randomized, controlled trial, 2) study sample included youth aged <19 years, 3) youth had type 1 diabetes, 4) study reported results on glycemic control; and 5) study reported use of adherence- or self-management-promoting components.The 15 studies included 997 youth with type 1 diabetes. The mean effect size for pre- to posttreatment change for the intervention versus control group comparison was 0.11 (95% CI -0.01 to 0.23). This is a small effect, demonstrating very modest improvements in glycemic control. However, analysis for the pre- to posttreatment effects for the intervention group alone did show significant variability [Q(14) = 33.11; P < 0.05]. Multicomponent interventions, those that targeted emotional, social, or family processes that facilitate diabetes management, were more potent than interventions just targeting a direct, behavioral process (e.g., increase in blood glucose monitoring frequency).Interventions that focus on direct, behavioral processes and neglect emotional, social, and family processes are unlikely to have an impact on glycemic control; multicomponent interventions showed more robust effects on A1C. Future clinical research should focus on refining interventions and gathering more efficacy and effectiveness data on health outcomes of the pediatric patients treated with these interventions.
Methionine Aminopeptidase 2 Inhibition Is an Effective Treatment Strategy for Neuroblastoma in Preclinical Models
Authors: Michael J. Morowitz, Rosalind Barr, Qun Wang, Rebecca King, Nicholas Rhodin, Bruce Pawel, Huaqing Zhao, Scott A. Erickson, George S. Sheppard, Jieyi Wang, John M. Maris, Suzanne Shusterman
Journal: Clinical Cancer Research (2005)

Abstract Tumor vascularity is correlated with an aggressive disease phenotype in neuroblastoma, suggesting that angiogenesis inhibitors may be a useful addition to current therapeutic strategies. We previously showed that the antiangiogenic compound TNP-470, an irreversible methionine aminopeptidase 2 (MetAP2) inhibitor, suppressed local and disseminated human neuroblastoma growth rates in murine models but had significant associated toxicity at the effective dose. We have recently shown that a novel, reversible MetAP2 inhibitor, A-357300, significantly inhibits CHP-134–derived neuroblastoma s.c. xenograft growth rate with a treatment-to-control (T/C) ratio at day 24 of 0.19 (P &amp;lt; 0.001) without toxicity. We now show that the combination of A-357300 with cyclophosphamide at the maximal tolerated dose sustained tumor regression with a T/C at day 48 of 0.16 (P &amp;lt; 0.001) in the CHP-134 xenograft model. A-357300 also significantly inhibited establishment and growth rate of hematogenous metastatic deposits following tail vein inoculation of CHP-134 cells and increased overall survival (P = 0.021). Lastly, A-357300 caused regression of established tumors in a genetically engineered murine model with progression-free survival in five of eight mice (P &amp;lt; 0.0001). There was no evidence of toxicity. These data show that MetAP2 may be an important molecular target for high-risk human neuroblastomas. We speculate that the growth inhibition may be through both tumor cell intrinsic and extrinsic (antiangiogenic) mechanisms. The potential for a wide therapeutic index may allow for treatment strategies that integrate MetAP2 inhibition with conventional cytotoxic compounds.
Screening for left ventricular dysfunction using a hand‐carried cardiac ultrasound device
Authors: Eleni C. Vourvouri, Arend F.L. Schinkel, Jos R.T.C. Roelandt, Frans Boomsma, Georgios Sianos, Manolis Bountioukos, Fabiola B. Sozzi, Vittoria Rizzello, Jeroen J. Bax, Haralambos I. Karvounis, Don Poldermans
Journal: European Journal of Heart Failure (2003)
Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization
Authors: Alan S. Go, Glenn M. Chertow, Dongjie Fan, Charles E. McCulloch, Chi-yuan Hsu
Journal: New England Journal of Medicine (2004)

End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined.We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization.The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m2 of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 (95 percent confidence interval, 1.1 to 1.2), 1.8 with an estimated GFR of 30 to 44 ml per minute per 1.73 m2 (95 percent confidence interval, 1.7 to 1.9), 3.2 with an estimated GFR of 15 to 29 ml per minute per 1.73 m2 (95 percent confidence interval, 3.1 to 3.4), and 5.9 with an estimated GFR of less than 15 ml per minute per 1.73 m2 (95 percent confidence interval, 5.4 to 6.5). The adjusted hazard ratio for cardiovascular events also increased inversely with the estimated GFR: 1.4 (95 percent confidence interval, 1.4 to 1.5), 2.0 (95 percent confidence interval, 1.9 to 2.1), 2.8 (95 percent confidence interval, 2.6 to 2.9), and 3.4 (95 percent confidence interval, 3.1 to 3.8), respectively. The adjusted risk of hospitalization with a reduced estimated GFR followed a similar pattern.An independent, graded association was observed between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization in a large, community-based population. These findings highlight the clinical and public health importance of chronic renal insufficiency.
Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy
Authors: Hans-Henrik Parving, Frederik Persson, Julia B. Lewis, Edmund J. Lewis, Norman K. Hollenberg
Journal: New England Journal of Medicine (2008)

Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries. We evaluated the renoprotective effects of dual blockade of the renin-angiotensin-aldosterone system by adding treatment with aliskiren, an oral direct renin inhibitor, to treatment with the maximal recommended dose of losartan (100 mg daily) and optimal antihypertensive therapy in patients who had hypertension and type 2 diabetes with nephropathy.We enrolled 599 patients in this multinational, randomized, double-blind study. After a 3-month, open-label, run-in period during which patients received 100 mg of losartan daily, patients were randomly assigned to receive 6 months of treatment with aliskiren (150 mg daily for 3 months, followed by an increase in dosage to 300 mg daily for another 3 months) or placebo, in addition to losartan. The primary outcome was a reduction in the ratio of albumin to creatinine, as measured in an early-morning urine sample, at 6 months.The baseline characteristics of the two groups were similar. Treatment with 300 mg of aliskiren daily, as compared with placebo, reduced the mean urinary albumin-to-creatinine ratio by 20% (95% confidence interval, 9 to 30; P<0.001), with a reduction of 50% or more in 24.7% of the patients who received aliskiren as compared with 12.5% of those who received placebo (P<0.001). A small difference in blood pressure was seen between the treatment groups by the end of the study period (systolic, 2 mm Hg lower [P=0.07] and diastolic, 1 mm Hg lower [P=0.08] in the aliskiren group). The total numbers of adverse and serious adverse events were similar in the groups.Aliskiren may have renoprotective effects that are independent of its blood-pressure-lowering effect in patients with hypertension, type 2 diabetes, and nephropathy who are receiving the recommended renoprotective treatment. (ClinicalTrials.gov number, NCT00097955 [ClinicalTrials.gov].).
Isolated Familial Hypogonadotropic Hypogonadism and a<i>GNRH1</i>Mutation
Authors: Jérôme Bouligand, Cristina Ghervan, Javier A. Tello, Sylvie Brailly-Tabard, Sylvie Salenave, Philippe Chanson, Marc Lombès, Robert P. Millar, Anne Guiochon-Mantel, Jacques Young
Journal: New England Journal of Medicine (2009)

We investigated whether mutations in the gene encoding gonadotropin-releasing hormone 1 (GNRH1) might be responsible for idiopathic hypogonadotropic hypogonadism (IHH) in humans. We identified a homozygous GNRH1 frameshift mutation, an insertion of an adenine at nucleotide position 18 (c.18-19insA), in the sequence encoding the N-terminal region of the signal peptide-containing protein precursor of gonadotropin-releasing hormone (prepro-GnRH) in a teenage brother and sister, who had normosmic IHH. Their unaffected parents and a sibling who was tested were heterozygous. This mutation results in an aberrant peptide lacking the conserved GnRH decapeptide sequence, as shown by the absence of immunoreactive GnRH when expressed in vitro. This isolated autosomal recessive GnRH deficiency, reversed by pulsatile GnRH administration, shows the pivotal role of GnRH in human reproduction.
MECHANISM OF THE LYSIS OF PNEUMOCOCCI BY FREEZING AND THAWING, BILE, AND OTHER AGENTS
Authors: René J. Dubos
Journal: The Journal of Experimental Medicine (1937)

Pneumococci, living or dead, are soluble in bile when: (a) the autolytic enzymes are still present in a potentially active form; (b) conditions are favorable for enzymatic action. Bile solubility of pneumococci involves as a necessary step one, or a few, of the many stages of the autolytic complex. These observations hold true for the disruption of pneumococci by freezing and thawing, by previous desiccation with cold acetone, and by dilute solutions of antiseptics. A possible mechanism is discussed to account for these forms of lysis.
MAST CELLS AS SOURCES OF TISSUE HISTAMINE
Authors: Helen Tredway Graham, Oliver H. Lowry, Nancy Wahl, Martha K. Priebat
Journal: The Journal of Experimental Medicine (1955)

Enumeration of mast cells and determination of histamine in sections of dog skin and dog lung have shown that the regions of the tissue rich in mast cells are also rich in histamine. In the skin, the outer layers of the dermis contain higher concentrations of histamine and mast cells than any other region. Average values of the histamine content and mast cell count for dog liver, heart, muscle, and kidney, and for beef liver parenchyma and capsule, also exhibit a positive relationship between these two parameters, although the amount of histamine found per mast cell varied from 7 µµg. in dog skin to 32 µµg. in beef liver capsule. When the size of the mast cells was taken into account, the intracellular concentration of histamine was found to be of the same order (about 0.4 molar) for all the tissues examined except skin and kidney. In both dog skins analyzed, the intracellular concentration was about 0.1 molar. In kidney both mast cell and histamine values were too low for accurate estimation. The concentration of histamine in the mast cells investigated was much greater than the concentration in human basophils, the blood elements richest in histamine. The mechanism of the localization of histamine in mast cells is briefly considered.
Rorγt+ innate lymphocytes and γδ T cells initiate psoriasiform plaque formation in mice
Authors: Stanislav Pantelyushin, Stefan Haak, Barbara Ingold, Paulina Kulig, Frank L. Heppner, Alexander A. Navarini, Burkhard Becher
Journal: Journal of Clinical Investigation (2012)

Psoriasis is a common, relapsing inflammatory skin disease characterized by erythematous scaly plaques. Histological manifestations of psoriasis include keratinocyte dysregulation and hyperproliferation, elongated rete ridges, and inflammatory infiltrates consisting of T cells, macrophages, dendritic cells, and neutrophils. Despite the availability of new effective drugs to treat psoriasis, the underlying mechanisms of pathogenesis are still poorly understood. Recent studies have shown that Aldara cream, used to treat benign skin abnormalities, triggers psoriasis-like disease in humans and mice and have implicated Th17 cells in disease initiation. Using this as a model, we found a predominant role for the Th17 signature cytokines IL-17A, IL-17F, and IL-22 in psoriasiform plaque formation in mice. Using gene-targeted mice, we observed that loss of Il17a, Il17f, or Il22 strongly reduced disease the severity of psoriasis. However, we found that Th17 cells were not the primary source of these pathogenic cytokines. Rather, IL-17A, IL-17F, and IL-22 were produced by a skin-invading population of γδ T cells and RORγt(+) innate lymphocytes. Furthermore, our findings establish that RORγt(+) innate lymphocytes and γδ T cells are necessary and sufficient for psoriatic plaque formation in an experimental disease model that closely resembles human psoriatic plaque formation.
NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis (NORMIMS study): a randomised, placebo-controlled trial
Authors: Per Soelberg Sorensen, Svein Ivar Mellgren, Anders Svenningsson, Irina Elovaara, Jette Lautrup Frederiksen, Antonie Giaever Beiske, Kjell-Morten Myhr, Lise Vejby Søgaard, Inge Christoffer Olsen, Magnhild Sandberg-Wollheim
Journal: The Lancet Neurology (2009)
Antituberculosis drug resistance rates in patients newly diagnosed with TB in Istanbul
Authors: Ogun Sezer, Faruk Ciftci, Erkan Bozkanat, Tuncer Ozkisa, Hatice Kaya, Tuba Ursavas, Zafer Kartaloglu
Journal: European Respiratory Journal (2012)

Background: Our hospital serves about 70% of all patients with tuberculosis (TB) in Turkish Armed Forces.

Aim: To assess drug resistance rates in soldier new patients with TB followed in our hospital

Method: Culture positive all new patients admitted to hospital between 1st of December 2006 and 1st of August 2010 enrolled into the study. 28 cases thought as relapse excluded the study. Drug susceptibilities in all patients were determined with BACTEC 460 TB.

Results: Drug susceptibility test was performed in 302 cases. Of all were men. Mean age was 21,7±2,1 years. 235 patients had smear and culture positivity. 67 had only culture positivity. 16 patients with pleural TB had culture positivity. 17,2% of all cases had at least one drug resistance. Isoniazid (H), streptomycine (S), rifampicin (R), and ethambutol (E) resistance rates were 14,3%, 1,9%, 4,6%, and 5,6% (respectively). 14 cases (4,6%) had multidrug resistance (H+R). H+S resistance was 0,7%. H+E resistance was 0,3%. H+R+E resistance was 1,5%. H+R+E+S resistance was 1,8%

Conclusion: In soldier patients, who are strongly representative of the young population in Turkey, H resistance was high. Others were acceptable levels.
Oral Glucose Tolerance Test: A Reliable Tool for Early Detection of Glucose Abnormalities in Patients With Acute Myocardial Infarction in Clinical Practice
Authors: Märit Wallander, Klas Malmberg, Anna Norhammar, Lars Rydén, Åke Tenerz
Journal: Diabetes Care (2007)

Previously undetected glucose abnormalities are common in patients with acute myocardial infarction (AMI). We evaluated long-term reliability of early glucometabolic classification of patients with AMI by repeated oral glucose tolerance tests (OGTTs).A glucometabolic OGTT-based classification was obtained in 122 patients by measuring capillary whole-blood glucose. The classification was performed on three occasions, before hospital discharge and 3 and 12 months thereafter.At discharge, 34, 31, and 34% were classified as having normal glucose tolerance, impaired glucose tolerance (IGT), or type 2 diabetes, respectively, and 93% of all patients with type 2 diabetes were still classified with type 2 diabetes (n = 27) or IGT (n = 12) after 12 months. The agreements between the OGTTs at discharge and 3 and 12 months were kappa = 0.35, P < 0.001, and kappa = 0.43, P < 0.001, respectively.The outcome of an OGTT performed in AMI patients at hospital discharge reliably informs on long-term glucometabolic state.
Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-paired
Authors: Stephen A. Brown, Dorothy Warburton, Lucia Y. Brown, Chih-yu Yu, Elizabeth R. Roeder, Sabine Stengel-Rutkowski, Raoul C.M. Hennekam, Maximilian Muenke
Journal: Nature Genetics (1998)
Targeting the miR-221–222/PUMA/BAK/BAX Pathway Abrogates Dexamethasone Resistance in Multiple Myeloma
Authors: Jian-Jun Zhao, Zhang-Bo Chu, Yu Hu, Jianhong Lin, Zhongqiu Wang, Meng Jiang, Ming Chen, Xujun Wang, Yue Kang, Yangsheng Zhou, Triona Ni Chonghaile, Melanie E. Johncilla, Yu-Tzu Tai, Jin Q. Cheng, Antony Letai, Nikhil C. Munshi, Kenneth C. Anderson, Ruben D. Carrasco
Journal: Cancer Research (2015)

Despite recent therapeutic advances that have doubled the median survival time of patients with multiple myeloma, intratumor genetic heterogeneity contributes to disease progression and emergence of drug resistance. miRNAs are noncoding small RNAs that play important roles in the regulation of gene expression and have been implicated in cancer progression and drug resistance. We investigated the role of the miR-221-222 family in dexamethasone-induced drug resistance in multiple myeloma using the isogenic cell lines MM1R and MM1S, which represent models of resistance and sensitivity, respectively. Analysis of array comparative genome hybridization data revealed gain of chromosome X regions at band p11.3, wherein the miR-221-222 resides, in resistant MM1R cells but not in sensitive MM1S cells. DNA copy number gains in MM1R cells were associated with increased miR-221-222 expression and downregulation of p53-upregulated modulator of apoptosis (PUMA) as a likely proapoptotic target. We confirmed PUMA mRNA as a direct target of miR-221-222 in MM1S and MM1R cells by both gain-of-function and loss-of-function studies. In addition, miR-221-222 treatment rendered MM1S cells resistant to dexamethasone, whereas anti-miR-221-222 partially restored the dexamethasone sensitivity of MM1R cells. These studies have uncovered a role for miR-221-222 in multiple myeloma drug resistance and suggest a potential therapeutic role for inhibitors of miR-221-222 binding to PUMA mRNA as a means of overcoming dexamethasone resistance in patients. The clinical utility of this approach is predicated on the ability of antisense miR-221-222 to increase survival while reducing tumor burden and is strongly supported by the metastatic propensity of MM1R cells in preclinical mouse xenograft models of multiple myeloma. Moreover, our observation of increased levels of miR-221-222 with decreased PUMA expression in multiple myeloma cells from patients at relapse versus untreated controls suggests an even broader role for miR-221-222 in drug resistance and provides a rationale for the targeting of miR-221-222 as a means of improving patient outcomes.
Calcitonin Induces 25-Hydroxyvitamin D3 1α-Hydroxylase mRNA Expression via Protein Kinase C Pathway in LLC-PK1 Cells
Authors: NORIKO YOSHIDA, TADASHI YOSHIDA, AKIRA NAKAMURA, TOSHIAKI MONKAWA, MATSUHIKO HAYASHI, TAKAO SARUTA
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The biosynthesis of 1α, 25-dihydroxyvitamin D 3 from 25-hydroxyvitamin D 3 is catalyzed by 25-hydroxyvitamin D 3 1α-hydroxylase (CYP27B1) in renal proximal tubules. It was recently demonstrated that LLC-PK 1 cells express CYP27B1 mRNA, which is regulated by intracellular cAMP but not vitamin D 3 . To clarify the effect of calcitonin on vitamin D 3 metabolism in vitro , LLC-PK 1 cells were incubated with hormonal factors, and expression of CYP27B1 mRNA was measured by quantitative reverse transcription-PCR. Calcitonin at 100 nmol/L significantly increased CYP27B1 mRNA expression by 24 h (271 ± 21% of control). Incubation with calcitonin over a range of 1 μmol/L to 1 pmol/L resulted in a concentration-dependent increase in CYP27B1 mRNA levels. It is known that the calcitonin receptor has dual intracellular signaling pathways, via protein kinases A and C. Both 500 μmol/L 8-bromo-cAMP, a protein kinase A activator, and 100 nmol/L phorbol 12-myristate 13-acetate, a protein kinase C activator, increased CYP27B1 mRNA levels at 24 h (207 ± 54 and 246 ± 58% of control, respectively). However, calcitonin-induced CYP27B1 mRNA expression was only inhibited by the protein kinase C inhibitors staurosporine and calphostin C. The protein kinase A inhibitors Rp-cAMPS at 10 and 100 μmol/L and H-89 at 10 μmol/L had no effect on the action of calcitonin, in spite of cAMP-activation by calcitonin. The present data suggest that calcitonin upregulates CYP27B1 mRNA expression via the protein kinase C pathway in LLC-PK 1 cells.
Phosphatidylinositol 3'-kinase and MAPK/ERK kinase 1/2 differentially regulate expression of vascular endothelial growth factor in human malignant astrocytoma cells
Authors: Stacy A. Woods, C. Jane McGlade, Abhijit Guha
Journal: Neuro-Oncology (2002)

Malignant astrocytomas are characterized by extensive vascularization attributed to increased expression of the angiogenic cytokine vascular endothelial growth factor (VEGF). VEGF is elevated in astrocytomas under normal oxygen conditions and undergoes induction in hypoxic stress. Prior studies have shown that both the phosphatidylinositol 3-kinase (PI3-kinase) and MEK1/2 (MAPK/ERK kinase 1/2) pathways promote proliferation of astrocytoma cells and growth of astrocytic tumors. Whether these pathways regulate growth by modulating angiogenesis as well as proliferation is not clear. In this study, pharmacologic inhibitors were used to specifically inhibit PI3-kinase and MEK1/2 activity in human malignant astrocytoma cell lines, and their effects on VEGF expression were determined. Northern blot analysis of VEGF messenger RNA (mRNA) from cells treated with inhibitors demonstrated cell line-specific responses. The PI3-kinase pathway regulated both the normoxic expression and hypoxic induction of VEGF in 2 cell lines, whereas MEK1/2 regulated only the normoxic expression in the same 2 lines. The third cell line showed no change in VEGF mRNA with inhibition of either of these 2 pathways. This study suggests that modulation of signaling pathways implicated in proliferation of astrocytoma cell lines may have varying effects in vivo depending on the role these pathways play in regulating tumor angiogenesis.
Heat Wave
Authors: Karen E. Smoyer Tomic
Journal: JAMA (2003)

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