tbuckley/cabot-search huggingface dataset:
Age-related differences in the expression of proto-oncogene and contractile protein genes in response to pressure overload in the rat myocardium.
Authors: T Takahashi, H Schunkert, S Isoyama, J Y Wei, B Nadal-Ginard, W Grossman, S Izumo
Journal: Journal of Clinical Investigation (1992)

Cardiac adaptation to hemodynamic stress involves both quantitative (hypertrophy) and qualitative (pattern of gene expression) changes. Our previous studies have shown that advancing age in the rat is associated with diminished capacity to develop left ventricular hypertrophy in response to either ascending aortic constriction (AoC). In this study, we examined whether the expression of protooncogenes and contractile protein genes in response to AoC differs between adult (9-mo-old) and old (18-mo-old) rats. RNA was isolated from the left ventricles of AoC animals of both age groups subjected to a similar hemodynamic stress. Immediately after AoC, the levels of the ventricular expression of c-fos and c-jun protooncogenes were markedly lower in the old rats than in the adult animals. 5 d after the operation, the ratio of beta- to alpha-myosin heavy chain mRNAs increased significantly after AoC in both age groups. In contrast, AoC was associated with a marked reduction in the levels of mRNAs encoding sarcoplasmic reticulum Ca(2+)-ATPase (by 69%) and cardiac calsequestrin (by 49%) in the old rats but not in the adults. The mRNAs encoding atrial natriuretic factor and skeletal alpha-actin increased in response to AoC only in the adult rats. There were no significant differences in expression of the cardiac alpha-actin mRNA among the experimental groups. These data suggest that (a) the expression of protooncogenes in response to acute pressure overload is significantly reduced in the aged rats and (b) the pattern of expression of the contractile protein gene in response to AoC in the old rats differs qualitatively as well as quantitatively from that in younger animals. These age-related differences may play a role in the higher frequency of heart failure in the aged during hemodynamic stress.
Quantitative Studies of Microcirculatory Structure and Function
Authors: BENJAMIN W. ZWEIFACH
Journal: Circulation Research (1974)

A systematic study was made of capillary pressures in the microvascular bed of the mesentery of the cat. Simultaneous recordings were made with two micropipettes using a modification of the Wiederhielm servo-null system. All of the measurements were then referred to their specific location in the capillary bed by photographically reconstructing discrete networks. Pressures in different capillary branches within a given network ranged from 40 mm Hg to as low as 24 mm Hg. There was no obvious pattern in the distribution of high-pressure vessels relative to low-pressure vessels. When capillary pressure was measured in a selected vessel and averaged over a period of several minutes, it remained constant (±3 mm Hg), despite much greater fluctuations in the precapillary and postcapillary vessels. A number of different procedures was used to obtain average values for capillary pressure in a given network. Estimates of capillary pressure from venous wedge pressures in the mesentery were related to the actual capillary pressure, but the precise proportionality of the two pressures was not the same in different preparations. Possibly, the estimates of average capillary pressure based on direct measurements were higher than those obtained indirectly from calculations of fluid exchange because other factors affecting the latter were not adequately considered.
The Hormonal Control of Testicular Descent
Authors: J. M. HUTSON, P. K. DONAHOE
Journal: Endocrine Reviews (1986)

Journal Article The Hormonal Control of Testicular Descent Get access J. M. Hutson, J. M. Hutson 1Department of General Surgery and Research Foundation (J.M.H.), Royal Children's Hospital, Melbourne, Australia; and Division of Pediatric Surgery (P.K.D.), Department of Surgery, Pediatric Surgical Research Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114 *Address requests for reprints and all correspondence to: Mr. J. M. Hutson, Department of Surgery, Royal Children's Hospital, Flemington Road, Parkville, Victoria, 3052 Australia. Search for other works by this author on: Oxford Academic Google Scholar P. K. Donahoe P. K. Donahoe 1Department of General Surgery and Research Foundation (J.M.H.), Royal Children's Hospital, Melbourne, Australia; and Division of Pediatric Surgery (P.K.D.), Department of Surgery, Pediatric Surgical Research Laboratory, Massachusetts General Hospital, Boston, Massachusetts 02114 Search for other works by this author on: Oxford Academic Google Scholar Endocrine Reviews, Volume 7, Issue 3, 1 August 1986, Pages 270–283, https://doi.org/10.1210/edrv-7-3-270 Published: 01 August 1986
THE OCCURRENCE OF ACUTE PNEUMONIA DURING TREATMENT WITH ARSENIC
Authors: F. P. Weber
Journal: BMJ (1913)

ACUTE PNEUMONIA DURING ARSENICAL TREATMENT.[MTfE BRITM.337 acquired instability of tlle normal relationships which govern secretory activities.However this may be., there is a strong famlily resernblance between Raynaud's disease, rheumatoid arthritis, and exophtlhalmic goitre.Whetlher there is any etiological or pathogenic factor common to tllose diseases remains to be seen.At the present time the
Long QT syndrome, implantable cardioverter defibrillator (ICD) and competitive sport participation: when science overcomes ethics
Authors: Antonio Pelliccia
Journal: British Journal of Sports Medicine (2013)

We saw with great interest the article “Return to play? Athletes with congenital long QT syndrome” recently published in this journal,1 describing the outcome of adolescents with long QT syndrome (LQTS) exposed to regular exercise training and sport participation for a 5-year period.

The authors claim that this experience represents ground for the revision of existing criteria of the Bethesda Conference (BC) #36 and European Society of Cardiology (ESC) recommendations regarding sport participation of young patients with LQTS.2 ,3 For this reason, we believed it appropriate to articulate pertinent considerations relative to their unique experience.

The novel observation refers to LQTS genotype-positive–phenotype-negative asymptomatic children actively involved in varied sport programmes. None incurred adverse events or developed cardiac symptoms in the 5-year period, supporting the substantial benign nature of this condition. This observation substantiates the clinical perception that gene abnormality, per se, should not be viewed as disease and, by showing the absence of significant risk for individuals with no symptoms and normal QTc interval (mean, 0.44 s in this subset), reassures clinicians of the favourable outcome of these young ‘patients’.

The present experience supports the concept that participation in sport activities (at youth league and high-school) does not convey increased risk and is not associated with the occurrence of adverse events in …
Impaired inhibitory action of corticosteroids on chemokine expression induced by TNFα in airway smooth muscle (ASM) cells from patients with severe asthma
Authors: Latifa Chachi, Omar Tliba, Adelina Gavrila, Christopher Brightling, Yassine Amrani
Journal: European Respiratory Journal (2013)

Although the mechanisms mediating corticosteroid resistance in severe asthma are still unknown, evidence suggests the existence of corticosteroid insensitive pathways in ASM cells. Here we investigated the sensitivity of TNF-induced chemokine production by human ASM cells to corticosteroids in healthy controls and patients with mild and severe asthma. Cells pre-treated with fluticasone (FP) and dexamethasone (Dex) for 2 hours were exposed to TNF (10 ng/ml) for 24 hours. Chemokine levels were assessed in cell supernatants using ELISA. TNF induced CXCL10 and CLL5 production in all subjects irrespective of disease severity. Net increases in CCL5 levels were 3593 ± 395, 5019 ± 125 pg/ml and 5832 ± 1705 pg/ml in ASM cells from healthy controls (n=3), and patients with mild (n=4) and severe asthma (n=3). Net increases in CXCL10 levels were 12956 ± 1838, 14528 ± 2350 pg/ml and 25327 ± 6816 pg/ml in ASM cells from healthy controls (n=3), and patients with mild (n=4) and severe asthma (n=3). Both FP and Dex (0.1-1000 nM) dose-dependently inhibited TNF-induced production of CXCL10 and CCL5 in healthy subjects reaching a complete inhibition at 100 nM (p
Endogenous production of carbon monoxide in normal and erythroblastotic newborn infants
Authors: M. Jeffrey Maisels, Ambadas Pathak, Nicholas M. Nelson, David G. Nathan, Clement A. Smith
Journal: Journal of Clinical Investigation (1971)

The endogenous production of carbon monoxide ( V(CO)) in newborn infants was measured by serial determinations of blood carboxyhemoglobin during rebreathing in a closed system. Mean V(CO) in nine full-term infants was 13.7 +/-3.6 mul CO/kg per hr (SD), and in four erythroblastotic infants V(CO) ranged from 37 to 154 mul CO/kg per hr preceding exchange transfusion. Mean red cell life-span (MLS) and total bilirubin production were calculated from V(CO). MLS in normal newborns was 88 +/-15 days (SD), and bilirubin production was 8.5 +/-2.3 mg/kg per 24 hr. This is more than twice the amount of bilirubin normally produced in the adult per kilogram of body weight. Normal infants achieved a net excretion of bilirubin of at least 5.6 +/-2.3 mg/kg per 24 hr (SD) as calculated from the bilirubin production and the measured rise in serum bilirubin concentration.The measurement of V(CO) should prove valuable in the study of red blood cell survival and bilirubin metabolism in the newborn infant.
In vitro and in vivo protein delivery from in situ forming poly(ethylene glycol)–poly(lactide) hydrogels
Authors: Christine Hiemstra, Zhiyuan Zhong, Sophie R. Van Tomme, Mies J. van Steenbergen, John J.L. Jacobs, Willem Den Otter, Wim E. Hennink, Jan Feijen
Journal: Journal of Controlled Release (2007)
B cell clonality in gastric lymphoid tissues of patients with Sjogren's syndrome.
Authors: G F Ferraccioli, D Sorrentino, S De Vita, L Casatta, A Labombarda, C Avellini, R Dolcetti, D Di Luca, C A Beltrami, M Boiocchi, E Bartoli
Journal: Annals of the Rheumatic Diseases (1996)

To determine the prevalence of mucosa associated lymphoid tissue (MALT) in the stomach and of a possible antigen driven proliferation, in patients with Sjögren's syndrome (SS).Twenty one patients with primary SS and 80 dyspeptic controls underwent upper endoscopy. Lymphoid tissue and Helicobacter pylori were assessed by histopathological analysis. Epstein-Barr virus (EBV) or human herpes virus-6 (HHV-6) genome were studied by polymerase chain reaction (PCR) DNA amplification. Two PCR VDJ procedures were used to detect immunoglobulin heavy chain (IgH) gene rearrangement.Organised MALT was found in 33.3% of the patients, compared with 21.5% of the controls (NS). H pylori infection was seen in 71% of patients and 63% of controls. Genomic EBV or HHV-6 was found in a minor portion of SS gastric tissues. B cell expansion was detected in nine of the 21 patients. Infectious agents in the stomach might have contributed to B cell clonality only in 55.5% of the cases. No strict relationship was found between lymphoid follicles and clonality.Lymphoid accumulation in the gastric mucosa is common in Sjögren's syndrome, but full evidence for an antigen driven B cell expansion could not be demonstrated. Only a portion of those with clonal B cell expansion had evidence of an infectious agent. Other unknown infectious agents or factors related to the underlying disease (autoantigen) and its tissue environment may have a further role as possible causes of B clonal expansion in the gastric mucosa.
Nonsteroidal Anti-inflammatory Drugs Induce Colorectal Cancer Cell Apoptosis by Suppressing 14-3-3ε
Authors: Jun-Yang Liou, Dipak Ghelani, Sam Yeh, Kenneth K. Wu
Journal: Cancer Research (2007)

Abstract To determine the role of 14-3-3 in colorectal cancer apoptosis induced by nonsteroidal anti-inflammatory drugs (NSAIDs), we evaluated the effects of sulindac on 14-3-3ε protein expression in colorectal cancer cells. Sulindac sulfide inhibited 14-3-3ε proteins in HT-29 and DLD-1 cells in a time- and concentration-dependent manner. Sulindac sulfone at 600 μmol/L inhibited 14-3-3ε protein expression in HT-29. Indomethacin and SC-236, a selective cyclooxygenase-2 (COX-2) inhibitor, exerted a similar effect as sulindac. Sulindac suppressed 14-3-3ε promoter activity. As 14-3-3ε promoter activation is mediated by peroxisome proliferator–activated receptor δ (PPARδ), we determined the correlation between 14-3-3ε inhibition and PPARδ suppression by NSAIDs. Sulindac sulfide inhibited PPARδ protein expression and PPARδ transcriptional activity. Overexpression of PPARδ by adenoviral transfer rescued 14-3-3ε proteins from elimination by sulindac or indomethacin. NSAID-induced 14-3-3ε suppression was associated with reduced cytosolic Bad with elevation of mitochondrial Bad and increase in apoptosis which was rescued by Ad-PPARδ transduction. Stable expression of 14-3-3ε in HT-29 significantly protected cells from apoptosis. Our findings shed light on a novel mechanism by which NSAIDs induce colorectal cancer apoptosis via the PPARδ/14-3-3ε transcriptional pathway. These results suggest that 14-3-3ε is a target for the prevention and therapy of colorectal cancer. [Cancer Res 2007;67(7):3185–91]
Diabetes and physical disability among older U.S. adults.
Authors: E W Gregg, G L Beckles, D F Williamson, S G Leveille, J A Langlois, M M Engelgau, K M Narayan
Journal: Diabetes Care (2000)

To estimate the prevalence of physical disability associated with diabetes among U.S. adults > or =60 years of age.We analyzed data from a nationally representative sample of 6,588 community-dwelling men and women > or =60 years of age who participated in the Third National Health and Nutrition Examination Survey. Diabetes and comorbidities (coronary heart disease, intermittent claudication, stroke, arthritis, and visual impairment) were assessed by questionnaire. Physical disability was assessed by self-reported ability to walk one-fourth of a mile, climb 10 steps, and do housework. Walking speed, lower-extremity function, and balance were assessed using physical performance tests.Among subjects > or =60 years of age with diabetes, 32% of women and 15% of men reported an inability to walk one-fourth of a mile, climb stairs, or do housework compared with 14% of women and 8% of men without diabetes. Diabetes was associated with a 2- to 3-fold increased odds of not being able to do each task among both men and women and up to a 3.6-fold increased risk of not being able to do all 3 tasks. Among women, diabetes was also associated with slower walking speed, inferior lower-extremity function, decreased balance, and an increased risk of falling. Of the >5 million U.S. adults > or =60 years of age with diabetes, 1.2 million are unable to do major physical tasks.Diabetes is associated with a major burden of physical disability in older U.S. adults, and these disabilities are likely to substantially impair their quality of life.
Novel Nanosensors for Rapid Analysis of Telomerase Activity
Authors: Jan Grimm, J Manuel Perez, Lee Josephson, Ralph Weissleder
Journal: Cancer Research (2004)

Abstract Elevated telomerase levels are found in many malignancies, offering an attractive target for therapeutic intervention and diagnostic or prognostic purposes. Here we describe the use of a novel nanosensor developed for rapid screens of telomerase activity in biological samples. The technique utilizes magnetic nanoparticles that, on annealing with telomerase synthesized TTAGGG repeats, switch their magnet state, a phenomenon readily detectable by magnetic readers. We tested the efficacy of different telomerase inhibitors in crude human and murine samples and show that phosphorylation of telomerase regulates its activity. High-throughput adaptation of the technique by magnetic resonance imaging allowed processing of hundreds of samples within tens of minutes at ultrahigh sensitivities. Together, these studies establish and validate a novel and powerful tool for rapidly sensing telomerase activity and provide the rationale for developing analogous magnetic nanoparticles for in vivo sensing.
Salvage Radioimmunotherapy With Murine Iodine-131–Labeled Antitenascin Monoclonal Antibody 81C6 for Patients With Recurrent Primary and Metastatic Malignant Brain Tumors: Phase II Study Results
Authors: David A. Reardon, Gamal Akabani, R. Edward Coleman, Allan H. Friedman, Henry S. Friedman, James E. Herndon, Roger E. McLendon, Charles N. Pegram, James M. Provenzale, Jennifer A. Quinn, Jeremy N. Rich, James J. Vredenburgh, Annick Desjardins, Sri Guruangan, Michael Badruddoja, Jeanette M. Dowell, Terence Z. Wong, Xiao-Guang Zhao, Michael R. Zalutsky, Darell D. Bigner
Journal: Journal of Clinical Oncology (2005)

To assess the efficacy and toxicity of intraresection cavity iodine-131-labeled murine antitenascin monoclonal antibody 81C6 (131I-m81C6) among recurrent malignant brain tumor patients.In this phase II trial, 100 mCi of 131I-m81C6 was injected directly into the surgically created resection cavity (SCRC) of 43 patients with recurrent malignant glioma (glioblastoma multiforme [GBM], n = 33; anaplastic astrocytoma [AA], n = 6; anaplastic oligodendroglioma [AO], n = 2; gliosarcoma [GS], n = 1; and metastatic adenocarcinoma, n = 1) followed by chemotherapy.With a median follow-up of 172 weeks, 63% and 59% of patients with GBM/GS and AA/AO tumors were alive at 1 year. Median overall survival for patients with GBM/GS and AA/AO tumors was 64 and 99 weeks, respectively. Ten patients (23%) developed acute hematologic toxicity. Five patients (12%) developed acute reversible neurotoxicity. One patient (2%) developed irreversible neurotoxicity. No patients required reoperation for radionecrosis.In this single-institution phase II study, administration of 100 mCi of 131I-m81C6 to recurrent malignant glioma patients followed by chemotherapy is associated with a median survival that is greater than that of historical controls treated with surgery plus iodine-125 brachytherapy. Furthermore, toxicity was acceptable. Administration of a fixed millicurie dose resulted in a wide range of absorbed radiation doses to the SCRC. We are now conducting a phase II trial, approved by the US Food and Drug Administration, using patient-specific 131I-m81C6 dosing, to deliver 44 Gy to the SCRC followed by standardized chemotherapy. A phase III multicenter trial with patient-specific dosing is planned.
Mycophenolate Mofetil Therapy in Lupus Nephritis
Authors: MARY ANNE DOOLEY, FERNANDO G. COSIO, PATRICK H. NACHMAN, MICHAEL E. FALKENHAIN, SUSAN L. HOGAN, RONALD J. FALK, LEE A. HEBERT
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Controlled clinical trials in renal transplantation have demonstrated that mycophenolate mofetil is well tolerated and has lower renal transplant rejection rates than azathioprine regimens. This study reports on the clinical experiences at two institutions with mycophenolate mofetil (MMF) for severe lupus nephritis. Twelve patients with relapsing or resistant nephritis previously treated with cyclophosphamide therapy and one patient who refused cyclophosphamide as initial therapy for diffuse proliferative nephritis but accepted MMF were included. During combined MMF/prednisone therapy, serum creatinine values remained normal or declined from elevated values: mean change in serum creatinine was -0.26 ± 0.46 μM/L, P = 0.039. Proteinuria significantly decreased: mean change in urine protein-to-creatinine ratios was -2.53 ± 3.76, P = 0.039. Decreased serum complement component C3 and elevated anti-double-stranded DNA antibody levels at baseline improved in some, but not all, patients. The mean initial dose of MMF was 0.92 g/d (range, 0.5 to 2 g/d). The mean duration of therapy was 12.9 mo (range, 3 to 24 mo). Adverse events included herpes simplex stomatitis associated with severe leukopenia ( n = 1), asymptomatic leukopenia ( n = 2), nausea/diarrhea ( n = 2), thinning of scalp hair ( n = 1), pancreatitis ( n = 1), and pneumonia without leukopenia ( n = 1). Recurrence of the pancreatitis led to discontinuation of MMF in this patient; all other adverse events resolved with dose reduction. It is concluded that MMF is well tolerated and has possible efficacy in controlling major renal manifestations of systemic lupus erythematosus. Controlled clinical trials are needed to define the role of MMF in the management of lupus nephritis.
Ischemic Preconditioning Prevents the Impairment of Hypoxic Coronary Vasodilatation Caused by Ischemia/Reperfusion
Authors: Eliana Giannella, Hans-Christian Mochmann, Roberto Levi
Journal: Circulation Research (1997)

Abstract We previously reported that hypoxic coronary vasodilatation (HCVD) is initiated by endothelial NO and sustained by adenosine. Prolonged ischemia/reperfusion impairs endothelium-dependent coronary vasodilatation, whereas transient ischemia (ie, preconditioning) protects the myocardium from subsequent ischemic events. Accordingly, we assessed whether prolonged ischemia/reperfusion impairs HCVD and whether preconditioning prevents this dysfunction. HCVD, elicited in isolated guinea pig hearts by a 1-minute exposure to 100% N 2 , consisted of an ≈70% increase in coronary flow associated with enhanced nitrite/nitrate and adenosine overflow (+40% and 5-fold, respectively). After 30-minute global ischemia and 20-minute reperfusion, HCVD was decreased by ≈60%, and the increases in nitrite/nitrate and adenosine overflow were abolished. Preconditioning (ie, three cycles of 5-minute global ischemia+5-minute reperfusion) prevented the impairment of HCVD and fully restored the increase in nitrite/nitrate overflow, but not that of adenosine. The protective effect of preconditioning was mimicked by perfusion with the adenosine A 1 receptor agonist N 6 -cyclopentyladenosine and prevented by the A 1 receptor antagonist N-0861. In addition, the A 3 receptor agonist N 6 -(3-iodobenzyl)adenosine-5′- N -methyl-carboxamide had a similar protective effect. The bradykinin B 2 receptor antagonist HOE 140 abolished the protective effect of preconditioning, whereas the NO synthase inhibitor N ω -methyl- l -arginine and the cycloxygenase inhibitor indomethacin did not. Our data indicate that preconditioning restores HCVD by a process that is triggered by activation of adenosine A 1 /A 3 and bradykinin B 2 receptors. The action of bradykinin is independent of NO and prostacyclin production. Once restored by preconditioning, HCVD is mediated by NO but no longer sustained by adenosine.
Two cases of suprascapular neuropathy in a family
Authors: M Ravindran
Journal: British Journal of Sports Medicine (2003)

Suprascapular entrapment neuropathy is well known in certain athletes, especially volleyball players. A brother and sister presented with right shoulder pain and wasting of the scapular muscles, particularly the infraspinatus. They had played volleyball for over six years and were forced to retire because of disability. Investigations showed involvement of the rhomboid muscles also, suggesting a probable extension of this syndrome to other nerves in the region such as the dorsal scapular nerve.