tbuckley/cabot-search huggingface dataset:
Clinical Aspects of Growth Hormone Deficiency in Adults
Authors: HANS DE BOER, GEERT-JAN BLOK, EDUARD A. VAN DER VEEN
Journal: Endocrine Reviews (1995)

GRADUALLY it is being realized that GH may have important physiological functions in adult man. Until recently, GH was only used to treat short statured children with established GH deficiency (GHD), and it remains common practice to discontinue GH replacement therapy when final height is reached. From a physiological point of view, it is questionable whether this approach is appropriate since it is well known that GH secretion persists throughout life (1–5). Daily GH production reaches its maximum during puberty (3–5). Thereafter, the GH secretion rate gradually decreases with age (3). Recently, several studies have shown that GHD in adults is associated with abnormalities in body composition (6–14), metabolic derangements (15–17), and suboptimal physical performance (18–20). Since recombinant technology has solved the limitations in GH supply, policies concerning GH replacement therapy in man may now be reconsidered. The studies performed in GHD adults uniformly suggest that these patients benefit from GH replacement therapy (19–34). However, it has also become clear that GH substitution is not without side effects. The purpose of this review is to describe and analyze the reported findings in untreated GHD adults as well as to evaluate the effects and side effects of GH replacement therapy. The pharmacological aspects of GH treatment in GHD subjects have been addressed recently (35).
The use of actigraphy in the monitoring of sleep and activity in ADHD: A meta-analysis
Authors: Franco De Crescenzo, Serena Licchelli, Marco Ciabattini, Deny Menghini, Marco Armando, Paolo Alfieri, Luigi Mazzone, Giuseppe Pontrelli, Susanna Livadiotti, Francesca Foti, Digby Quested, Stefano Vicari
Journal: Sleep Medicine Reviews (2015)
T lymphocytes specific for immunoglobulin allotype. II. Cloned Igh-1(b)- specific cytotoxic T cells
Authors: HR Snodgrass, MJ Bosma, DB Wilson
Journal: The Journal of Experimental Medicine (1981)

This study describes long-term-cultured lines and clones of cytotoxic T cells (Tc) with specificity for determinants of the Igh-1(b) immunoglobulin allotype. These Tc clones were initiated by repeated stimulation of immune spleen cells from BALB/c mice with an Igh-1(b)-producing myeloma, and then they were maintained in medium supplemented with mitogen-induced growth factors in the absence offurther antigenic stimulation . The lytic potency of these clones was 30-100-fold greater than the primary cultures from which they were derived, and specificity studies showed them to be lytic for Igh-1(b) targets and not for targets expressing Igh-1(a) or Igh-4(b), nor the lipopolysaccharide blasts . Finally, soluble preparations of Ig were tested for their ability to block lysis of labeled Igh-1(b)-expressing targets. The results showed that Igh-1(b) and not other immunoglobulin allotypes or isotypes could block lysis, and that the mechanism of lytic inhibition is due to Igh-1(b)-induced autolysis of the killer cells.
Deloading of the Left Ventricle by Ventricular Assist Device Normalizes Increased Expression of Endothelin ETA Receptors But Not Endothelin-Converting Enzyme-1 in Patients With End-Stage Heart Failure
Authors: H. Morawietz, M. Szibor, W. Goettsch, B. Bartling, M. Barton, S. Shaw, R. Koerfer, H.-R. Zerkowski, J. Holtz
Journal: Circulation (2000)

Ventricular assist devices (VAD) are implanted in patients with end-stage heart failure for bridging the time until heart transplantation, resulting in hemodynamic unloading of the failing heart, improved cardiac contractile and mitochondrial function, and reversal of cardiac hypertrophy. It is unknown whether VAD unloading may affect the cardiac endothelin (ET) system, which has been proposed as one of the putative pathomechanisms of heart failure.With the use of standard-calibrated, competitive reverse-transcription-polymerase chain reaction mRNA expression of components of the ET system was analyzed in left ventricular myocardium from nonfailing donor hearts, from failing hearts without and with ACE inhibitor therapy, and from patients with end-stage heart failure at the time of VAD implantation and 103+/-15 days after VAD implantation during removal with subsequent heart transplantation. ET receptor A (ET(A)) was markedly upregulated in failing human myocardium. This increased ET(A) expression was not affected by ACE inhibitor treatment but was normalized by VAD unloading. ET(A) expression before or after VAD implantation did not correlate with duration of VAD implantation or suppression of Pro-ANP mRNA. ET(B) mRNA expression was unaffected by heart failure or VAD. In contrast, increased ET-converting enzyme-1 mRNA and ET-1 peptide levels in failing myocardium were partially normalized by ACE inhibition but not by VAD unloading.We conclude that VAD implantation normalizes ET(A) expression in failing human left ventricular myocardium, probably as the result of the beneficial effects of VAD unloading.
<i>PIK3CA</i> Mutations in Colorectal Cancer Are Associated with Clinical Resistance to EGFR-Targeted Monoclonal Antibodies
Authors: Andrea Sartore-Bianchi, Miriam Martini, Francesca Molinari, Silvio Veronese, Michele Nichelatti, Salvatore Artale, Federica Di Nicolantonio, Piercarlo Saletti, Sara De Dosso, Luca Mazzucchelli, Milo Frattini, Salvatore Siena, Alberto Bardelli
Journal: Cancer Research (2009)

The monoclonal antibodies (moAb) panitumumab and cetuximab target the epidermal growth factor receptor (EGFR) and have proven valuable for the treatment of metastatic colorectal cancer (mCRC). EGFR-mediated signaling involves two main intracellular cascades: on one side KRAS activates BRAF, which in turn triggers the mitogen-activated protein kinases. On the other, membrane localization of the lipid kinase PIK3CA counteracts PTEN and promotes AKT1 phosphorylation, thereby activating a parallel intracellular axis. Constitutive activation of KRAS bypasses the corresponding signaling cascade and, accordingly, patients with mCRC bearing KRAS mutations are clinically resistant to therapy with panitumumab or cetuximab. We hypothesized that mutations activating PIK3CA could also preclude responsiveness to EGFR-targeted moAbs through a similar mechanism. Here, we present the mutational analysis of PIK3CA and KRAS and evaluation of the PTEN protein status in a cohort of 110 patients with mCRC treated with anti-EGFR moAbs. We observed 15 (13.6%) PIK3CA and 32 (29.0%) KRAS mutations. PIK3CA mutations were significantly associated with clinical resistance to panitumumab or cetuximab; none of the mutated patients achieved objective response (P = 0.038). When only KRAS wild-type tumors were analyzed, the statistical correlation was stronger (P = 0.016). Patients with PIK3CA mutations displayed a worse clinical outcome also in terms of progression-free survival (P = 0.035). Our data indicate that PIK3CA mutations can independently hamper the therapeutic response to panitumumab or cetuximab in mCRC. When the molecular status of the PIK3CA/PTEN and KRAS pathways are concomitantly ascertained, up to 70% of mCRC patients unlikely to respond to EGFR moAbs can be identified.
The cytotoxic T cell response to the male-specific histocompatibility antigen (H-Y) is controlled by two dominant immune response genes, one in the MHC, the other in the Tar alpha-locus.
Authors: R Epstein, G Sham, J Womack, J Yagüe, E Palmer, M Cohn
Journal: The Journal of Experimental Medicine (1986)

The genetic control of the cytotoxic T-cell response to the male histocompatibility antigen, H-Y, was analyzed in BALB/cKe(C) and SJL/J(J) which are both nonresponders. However, the (C X J)F1 hybrid is a responder. Therefore, two dominant complementing genes are involved. Analysis of a set of (C X J) recombinant inbred (RI) lines reveals that these two complementing gene products are a restricting element (R) encoded by the H-2 (MHC) locus on chromosome 17 and a subunit of the T-cell receptor (anti-R) encoded by the Tar alpha-locus on chromosome 14. The order and orientation of gene segments within the Tar alpha-locus has also been established relative to the chromosome 14 marker, Es-10. The existence of two RI strains which are recombinant at chromosome 14 has made it possible to determine that this order is Es-10--v alpha-1--v alpha-2--[C alpha--Np-2]--centromere. The implications of these data for the antigen-specific regulation of immune responsiveness are discussed in terms of the dual recognitive-single receptor model.
Quantitative Assays for Evaluation of HTLV-III Inactivation Procedures: Tri(N-butyl)phosphate:sodium cholate and β-Propiolactone
Authors: Alfred M. Prince, Bernard Horowitz, Herbert Dichtelmueller, Wolfgang Stephan, Robert C. Gallo
Journal: Cancer Research (1985)

Abstract  Human T-lymphotropic retrovirus type III (HTLV-III) can be quantitatively assayed for infectivity by inoculation of serial dilutions into cultures of the H-9 cell line and testing for reverse transcriptase in the culture supernatants. Sequential harvests revealed that 14 days of incubation of cultures fed twice weekly was sufficient to reveal maximal titers. Stocks prepared from unconcentrated H9:HTLV-IIIb supernatants have contained from 104.5 to 106.0 (TCID50)/ml. Stocks prepared by 100-fold concentration of such fluids by pelleting or by polyethylene glycol precipitation followed by pelleting onto sucrose cushions contained 106.0–106.5 TCID50/ml.  Preliminary studies are under way to utilize this system for evaluation of sterilization processes which can be applied to blood derivatives. Exposure of HTLV-III suspended in Factor VIII preparations to 0.3% tri(n-butyl)phosphate-0.2% sodium cholate resulted in inactivation of ≥104.5 TCID50 in 2.5 h at 27°C. Exposure of HTLV-III suspended in 4 g of γ-globulin per 100 ml to 0.14% β-propiolactone for 4 h at room temperature at pH 8.0 inactivated ≥104.5 TCID50. However, exposure to γ-globulin alone inactivated about 99% of HTLV-III infectivity.
Engraftment of engineered ES cell–derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium
Authors: Eugen Kolossov, Toktam Bostani, Wilhelm Roell, Martin Breitbach, Frank Pillekamp, Jens M. Nygren, Philipp Sasse, Olga Rubenchik, Jochen W. U. Fries, Daniela Wenzel, Caroline Geisen, Ying Xia, Zhongju Lu, Yaqi Duan, Ralf Kettenhofen, Stefan Jovinge, Wilhelm Bloch, Heribert Bohlen, Armin Welz, Juergen Hescheler, Sten Eirik Jacobsen, Bernd K. Fleischmann
Journal: The Journal of Experimental Medicine (2006)

Cellular cardiomyoplasty is an attractive option for the treatment of severe heart failure. It is, however, still unclear and controversial which is the most promising cell source. Therefore, we investigated and examined the fate and functional impact of bone marrow (BM) cells and embryonic stem cell (ES cell)–derived cardiomyocytes after transplantation into the infarcted mouse heart. This proved particularly challenging for the ES cells, as their enrichment into cardiomyocytes and their long-term engraftment and tumorigenicity are still poorly understood. We generated transgenic ES cells expressing puromycin resistance and enhanced green fluorescent protein cassettes under control of a cardiac-specific promoter. Puromycin selection resulted in a highly purified (&amp;gt;99%) cardiomyocyte population, and the yield of cardiomyocytes increased 6–10-fold because of induction of proliferation on purification. Long-term engraftment (4–5 months) was observed when co-transplanting selected ES cell–derived cardiomyocytes and fibroblasts into the injured heart of syngeneic mice, and no teratoma formation was found (n = 60). Although transplantation of ES cell–derived cardiomyocytes improved heart function, BM cells had no positive effects. Furthermore, no contribution of BM cells to cardiac, endothelial, or smooth muscle neogenesis was detected. Hence, our results demonstrate that ES-based cell therapy is a promising approach for the treatment of impaired myocardial function and provides better results than BM-derived cells.
Adjuvant Trastuzumab Induces Ventricular Remodeling Despite Aerobic Exercise Training
Authors: Mark J. Haykowsky, John R. Mackey, Richard B. Thompson, Lee W. Jones, D. Ian Paterson
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To examine the effect of aerobic training in mitigating trastuzumab-mediated left ventricular (LV) remodeling in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Experimental Design: Seventeen women (53 ± 7 years) with HER2-positive breast cancer did aerobic training during the first 4 months of adjuvant trastuzumab. Peak oxygen consumption and magnetic resonance imaging assessment of LV volumes, mass, and rest and peak (dobutamine stress) ejection fraction were assessed before and after 4 months of trastuzumab. Results: Participants attended 59% ± 32% of prescribed exercise sessions at 78% ± 6% of peak heart rate. Peak exercise heart rate, systolic and diastolic blood pressure, power output, and oxygen consumption were not different after training (all P-values &amp;gt; 0.05). Exercise adherence predicted change in peak oxygen consumption (r = 0.77; P = 0.000). Resting end-diastolic (pre: 120 ± 23 mL versus post: 133 ± 16 mL) and end-systolic volumes (pre: 44 ± 12 mL versus post: 55 ± 11 mL) and mass (pre: 108 ± 21 g versus post: 114 ± 18 g) increased, whereas ejection fraction (pre: 64% ± 4% versus post: 59% ± 4%) decreased from baseline to post-intervention (all P-values &amp;lt; 0.05). Peak ejection fraction was lower after 4 months (pre: 79 ± 4 versus post: 76 ± 6%; P = 0.087). Conclusion: Initiation of adjuvant trastuzumab therapy is associated with LV cavity dilation and reduced ejection fraction despite aerobic exercise training. The long-term consequences of trastuzumab-induced LV remodeling and the means to prevent LV dysfunction require further study.
Going with the flow: How shear stress signals the emergence of adult hematopoiesis
Authors: David Traver
Journal: The Journal of Experimental Medicine (2015)

The Journal of Experimental Medicine Communication between cells is vital for maintenance of immune homeostasis and is also required for rapid and effective immune responses.Nowhere is this balance of activity more important than at mucosal surfaces such as the respiratory tract, where resident cells must ignore potentially antigenic inhaled material while responding swiftly to clear viruses and bacteria.In this issue, Bourdonnay et al. describe a novel form of intercellular communication that helps to explain how alveolar macrophages and epithelial cells maintain pulmonary homeostasis.The function of SOCS proteins is to constrain JAK-STAT signaling and repress inflammatory reactions.We do not usually expect to find these intracellular signaling molecules in extracellular compartments, but Bourdonnay et al. showed that lung-resident alveolar macrophages (AMs) were able to secrete SOCS1 within exosomes and SOCS3 within extracellular microparticles.Uptake of these extracellular vesicles by alveolar epithelial cells (AECs) allowed SOCS1 and -3 to suppress STAT signaling following activation by cytokines.The authors demonstrated that this novel extracellular transfer system was promoted by IL-10 and PGE 2 and inhibited by LPS.The phenomenon was demonstrated in a number of model systems including both rats and mice and also, importantly, in human AMs.Moreover, secretion was not simply dependent on expression of SOCS3, because fibroblasts expressed high levels of SOCS3 but did not secrete it.Any in vitro finding needs to be robustly tested in vivo to demonstrate a physiologic effect.The authors showed that SOCS3 was abundant in bronchiolar lavage (BAL) even in naive mice; SOCS3 levels increased after administration of PGE 2 to the lungs and decreased after pulmonary delivery of LPS.Moreover, SOCS3 was retrieved from BAL from healthy human volunteers.Interestingly, exposure to cigarette smoke reduced levels of both SOCS1 and -3 in both mice and humans; so, smoking could lead to unchecked JAK-STAT activation, thereby contributing to inflammatory responses.Although it remains to be seen whether this particular form of epithelial-macrophage communication operates during respiratory infection, these data are important because they shed some light on the complex interactions that maintain homeostasis within the lung.It may be possible to exploit this system in order to down-regulate inflammation following infection and ultimately facilitate the restoration of immune homeostasis.
Young hospital doctors. West Germany.
Authors: H Waldman
Journal: BMJ (1973)

A 25-year-old man was found to have acute kidney injury (AKI) following ingestion of mephedrone. He presented to this local emergency department with worsening bilateral loin pain. He became oligoanuric, serum creatine peaked at 1214 µmol/l and he required several sessions of haemodialysis before kidney function began to improve. The mechanism of AKI and legal aspects of the use of mephedrone are discussed.
Interaction of Low-Dose Amphetamine Use with Schizophrenia in Outpatients: Three Case Reports
Authors: A. PRESTON WEST
Journal: American Journal of Psychiatry (1974)

The similarities between amphetamine psychosis and schizophrenia have been noted by several authors. Recently, an exacerbation of acute schizophrenia by amphetamine has been demonstrated. The case histories presented in this paper suggest that the dosages of amphetamine often prescribed for dieting may precipitate psychotic symptoms in outpatient schizophrenics who are not known to be clinically ill when the drugs are prescribed.
Phase I and pharmacokinetic study of 24-hour infusion 5-fluorouracil and leucovorin in patients with organ dysfunction
Authors: G.F. Fleming, R.L. Schilsky, L.P. Schumm, A. Meyerson, A.M. Hong, N.J. Vogelzang, M.J. Ratain
Journal: Annals of Oncology (2003)
Decreased Subcortical Cholinergic Arousal in Focal Seizures
Authors: Joshua E. Motelow, Wei Li, Qiong Zhan, Asht M. Mishra, Robert N.S. Sachdev, Geoffrey Liu, Abhijeet Gummadavelli, Zaina Zayyad, Hyun Seung Lee, Victoria Chu, John P. Andrews, Dario J. Englot, Peter Herman, Basavaraju G. Sanganahalli, Fahmeed Hyder, Hal Blumenfeld
Journal: Neuron (2015)
Characteristics of patients aged over 75 not seen during one year in general practice.
Authors: E I Williams
Journal: BMJ (1984)

A study was carried out in two large urban practices to determine the number of patients aged over 75 years who had had no contact with the primary care team during one year and to examine their medical and social characteristics. Although their general health was considered to be good, over half needed treatment or other action and half had no identifiable career.
Improvement of Electrophysiological Neuropathy After Islet Transplantation for Type 1 Diabetes: A 5-Year Prospective Study
Authors: Marie-Christine Vantyghem, Delphine Quintin, Robert Caiazzo, Clara Leroy, Violeta Raverdy, François Cassim, François Glowacki, Thomas Hubert, Valery Gmyr, Christian Noel, Julie Kerr-Conte, François Pattou
Journal: Diabetes Care (2014)

The consequences of islet transplantation (IT) on neuropathy remain unclear, especially since neurotoxic effects of tacrolimus have been reported (1). The restoration of a euglycemic state in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study and through alone or combined whole pancreas transplantation has been shown to halt the progression of diabetic neuropathy (2). A significant improvement of a nerve conduction velocity (NCV) score compared with baseline was observed after IT-after-kidney (IAK), without any difference from a control group of nine kidney-only transplanted patients (3). No significant improvement of NCV was noticed 3 years after IT-alone (ITA) in a crossover study compared with intensive medical therapy (4). There has been no study of cardiac autonomic neuropathy (CAN) after IT and the results after kidney-pancreas transplantation are discordant. The aim of our study is to describe the evolution of neuropathy after IT. This single-arm, 5-year prospective, longitudinal study included 21 type 1 diabetic patients who underwent IT (13 ITA, 8 IAK) in a single center. Immunosuppression was induced by interleukin-2 receptor antibodies and maintained with tacrolimus and sirolimus as described (5). The main study end …
MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy
Authors: Kensuke Kojima, Marina Konopleva, Ismael J. Samudio, Masato Shikami, Maria Cabreira-Hansen, Teresa McQueen, Vivian Ruvolo, Twee Tsao, Zhihong Zeng, Lyubomir T. Vassilev, Michael Andreeff
Journal: Blood (2005)

Abstract Although TP53 mutations are rare in acute myeloid leukemia (AML), inactivation of wild-type p53 protein frequently occurs through overexpression of its negative regulator MDM2 (murine double minute 2). Recently, small-molecule antagonists of MDM2, Nutlins, have been developed that inhibit the p53-MDM2 interaction and activate p53 signaling. Here, we study the effects of p53 activation by Nutlin-3 in AML cells. Treatment with MDM2 inhibitor triggered several molecular events consistent with induction of apoptosis: loss of mitochondrial membrane potential, caspase activation, phosphatidylserine externalization, and DNA fragmentation. There was a positive correlation in primary AML samples with wild-type p53 between baseline MDM2 protein levels and apoptosis induced by MDM2 inhibition. No induction of apoptosis was observed in AML samples harboring mutant p53. Colony formation of AML progenitors was inhibited in a dose-dependent fashion, whereas normal CD34+ progenitor cells were less affected. Mechanistic studies suggested that Nutlin-induced apoptosis was mediated by both transcriptional activation of proapoptotic Bcl-2 family proteins, and transcription-independent mitochondrial permeabilization resulting from mitochondrial p53 translocation. MDM2 inhibition synergistically enhanced cytotoxicity of cytosine arabinoside and doxorubicin in AML blasts but not in normal hematopoietic progenitor cells. p53 activation by targeting the p53-MDM2 interaction might offer a novel therapeutic strategy for AML that retain wild-type p53.
Association between short term exposure to fine particulate matter and heart rate variability in older subjects with and without heart disease
Authors: J. H. Sullivan, A. B. Schreuder, C. A. Trenga, S. L.-J. Liu, T. V. Larson, J. Q. Koenig, J. D. Kaufman
Journal: Thorax (2005)

<b>Background:</b> Short term increases in exposure to particulate matter (PM) air pollution are associated with increased cardiovascular morbidity and mortality. The mechanism behind this effect is unclear, although changes in autonomic control have been observed. It was hypothesised that increases in fine PM measured at the subjects’ home in the preceding hour would be associated with decreased high frequency heart rate variability (HF-HRV) in individuals with pre-existing cardiac disease. <b>Methods:</b> Two hundred and eighty five daily 20 minute measures of HRV (including a paced breathing protocol) were made in the homes of 34 elderly individuals with (n = 21) and without (n = 13) cardiovascular disease (CVD) over a 10 day period in Seattle between February 2000 and March 2002. Fine PM was continuously measured by nephelometry at the individuals’ homes. <b>Results:</b> The median age of the study population was 77 years (range 57–87) and 44% were male. Models that adjusted for health status, relative humidity, temperature, mean heart rate, and medication use did not find a significant association between a 10 μg/m<sup>3</sup> increase in 1 hour mean outdoor PM<sub>2.5</sub> before the HRV measurement and a change in HF-HRV power in individuals with CVD (3% increase in median HF-HRV (95% CI −19 to 32)) or without CVD (5% decrease in median HF-HRV (95% CI −34 to 36)). Similarly, no association was evident using 4 hour and 24 hour mean outdoor PM<sub>2.5</sub> exposures before the HRV measurement. <b>Conclusion:</b> No association was found between increased residence levels of fine PM and frequency domain measures of HRV in elderly individuals.