tbuckley/cabot-search huggingface dataset:
EFFECTS OF CEREBRAL ELECTROSHOCK ON EXPERIMENTAL NEUROSES IN CATS
Authors: JULES H. MASSERMAN, MARY GRIER JACQUES
Journal: American Journal of Psychiatry (1947)

Six cats were made experimentally neurotic and were then subjected to cerebral electroshocks comparable to those used in clinical therapy. All of these animals showed a marked disintegration of inhibitions, phobias, compulsions and other neurotic patterns, with emergence of simpler, more normally readaptive behavior which could be further improved by guidance, retraining, and other corrective procedures. However, all of the neurotic animals and two normal controls subjected to the electroshocks also showed an impaired capacity for complex adaptations, with subsequent recovery in only 2 of the animals. In no case, however, could these deficits be correlated with corresponding histopathologic changes in the brain. The significance of these observations in relation to the clinical use of shock therapy is briefly discussed.
Evolution of candidate transcriptional regulatory motifs since the human-chimpanzee divergence
Authors: Ian J Donaldson, Berthold Göttgens
Journal: Genome biology (2006)

Abstract Background Despite the recent completion of the chimpanzee genome project, few functionally significant sequence differences between humans and chimpanzees have thus far been identified. Alteration in transcriptional regulatory mechanisms represents an important platform for evolutionary change, suggesting that a significant proportion of functional human-chimpanzee sequence differences may affect regulatory elements. Results To explore this hypothesis, we performed genome-wide identification of conserved candidate transcription-factor binding sites that have evolved since the divergence of humans and chimpanzees. Analysis of candidate transcription-factor binding sites conserved between mouse and chimpanzee yet absent in human indicated that loss of candidate transcription-factor binding sites in the human lineage was not random but instead correlated with the biologic functions of associated genes. Conclusion Our data support the notion that changes in transcriptional regulation have contributed to the recent evolution of humans. Moreover, genes associated with mutated candidate transcription-factor binding sites highlight potential pathways underlying human-chimpanzee divergence.
Allogeneic Bone Marrow Transplantation for Chronic Myeloid Leukemia Using Sibling and Volunteer Unrelated Donors: A Comparison of Complications in the First 2 Years
Authors: David I. Marks
Journal: Annals of Internal Medicine (1993)

Objective: To compare the short- and medium-term complications (particularly infection) of bone marrow transplantation for chronic myeloid leukemia in patients with HLA-identical sibling donors or volunteer unrelated donors. Design: Retrospective review of two cohorts of patients. Setting: Tertiary referral center. Patients: One hundred three patients with chronic myeloid leukemia in first chronic phase. Intervention: Patients were treated with bone marrow transplantation using marrow from HLA-identical siblings (n = 57) and volunteer donors (n = 46). Main Results: In total, 68 patients survived a median of 22 months from bone marrow transplant (range, 7 to 81 months). The actuarial probabilities of overall survival and leukemia-free survival at 2 years for the sibling donor group were 73% (95% CI, 60% to 86%) and 72% (CI, 60% to 84%), respectively, and for the volunteer donor group, 47% (CI, 31% to 63%) and 42% (CI, 26% to 58%) (P = 0.07 and 0.05, respectively). However, after adjustment for duration of disease, overall and disease-free survival in the two donor groups did not differ significantly. A major problem was an increased incidence of severe viral infection in the volunteer unrelated donor group (19 episodes in 16 of 46 patients compared with 7 episodes in 7 of 57 sibling donor patients, P = 0.01). The actuarial incidence of chronic graft-versus-host disease (GVHD) was higher in volunteer unrelated donor patients (77% [CI, 63% to 91%] compared with 49% [CI, 35% to 63%]; P = 0.02) but that of acute GVHD was not. The median performance status of the survivors in the volunteer donor group is similar to that in the sibling donor group. The incidence of hematologic relapse in both groups so far is low. Conclusion: Results appear to justify the continued use of volunteer donors in chronic-phase chronic myeloid leukemia, but infection and chronic GVHD are still major problems.
Factors affecting inorganic mercury transport and toxicity in the isolated perfused proximal tubule.
Authors: R K Zalups, M K Robinson, D W Barfuss
Journal: Journal of the American Society of Nephrology (1991)

The effects of cysteine (80 microM), glutathione (80 microM), rabbit albumin (100 microM), and an ultrafiltrate of rabbit plasma on the toxicity and transport of inorganic mercury (Hg2+; 18.4 microM) in isolated perfused S1, S2, and S3 segments of the renal proximal tubule from the rabbit were studied. Cellular and tubular injuries were assessed qualitatively by light microscopy observations and quantitatively by the tubular leak of the volume marker 3H-glucose. The lumen-to-bath transport of inorganic mercury was assessed by measuring both the rate of disappearance of inorganic mercury from the luminal fluid and the rate of appearance of inorganic mercury in the bath. When glutathione was added to the perfusate containing the inorganic mercury, no signs of epithelial cell necrosis or injury were detected in any of the three segments of the proximal tubule. There was also an absence of or a decrease in cellular injury in the epithelium of the same tubular segments when either cysteine or the ultrafiltrate was present in the perfusate. However, when rabbit albumin and inorganic mercury were present in the perfusate, severe degenerative and necrotic changes occurred very rapidly in the epithelium of all three segments of the proximal tubule. In almost every instance where glutathione, cysteine, or the plasma ultrafiltrate were present in the perfusate, the disappearance flux of inorganic mercury from the tubular lumen into the tubular epithelium was lowered. It was concluded that glutathione, cysteine, and the ultrafiltrate of rabbit plasma provide isolated perfused S1, S2, and S3 segments of the proximal tubule varying degrees of protection from the toxic effects of inorganic mercury. This protection appears to be related to a decrease in the movement of inorganic mercury across the luminal membrane of the tubular epithelial cells.
Myostatin Regulates Energy Homeostasis in the Heart and Prevents Heart Failure
Authors: Nadine Biesemann, Luca Mendler, Astrid Wietelmann, Sven Hermann, Michael Schäfers, Marcus Krüger, Thomas Boettger, Thilo Borchardt, Thomas Braun
Journal: Circulation Research (2014)

Myostatin is a major negative regulator of skeletal muscle mass and initiates multiple metabolic changes, including enhanced insulin sensitivity. However, the function of myostatin in the heart is barely understood, although it is upregulated in the myocardium under several pathological conditions.Here, we aimed to decipher the role of myostatin and myostatin-dependent signaling pathways for cardiac function and cardiac metabolism in adult mice. To avoid potential counterregulatory mechanisms occurring in constitutive and germ-line-based myostatin mutants, we generated a mouse model that allows myostatin inactivation in adult cardiomyocytes.Cardiac MRI revealed that genetic inactivation of myostatin signaling in the adult murine heart caused cardiac hypertrophy and heart failure, partially recapitulating effects of the age-dependent decline of the myostatin paralog growth and differentiation factor 11. We found that myostatin represses AMP-activated kinase activation in the heart via transforming growth factor-β-activated kinase 1, thereby preventing a metabolic switch toward glycolysis and glycogen accumulation. Furthermore, myostatin stimulated expression of regulator of G-protein signaling 2, a GTPase-activating protein that restricts Gaq and Gas signaling and thereby protects against cardiac failure. Inhibition of AMP-activated kinase in vivo rescued cardiac hypertrophy and prevented enhanced glycolytic flow and glycogen accumulation after inactivation of myostatin in cardiomyocytes.Our results uncover an important role of myostatin in the heart for maintaining cardiac energy homeostasis and preventing cardiac hypertrophy.
A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy
Authors: Xueli Yuan, Jesus Paez-Cortez, Isabela Schmitt-Knosalla, Francesca D'Addio, Bechara Mfarrej, Michela Donnarumma, Antje Habicht, Michael R. Clarkson, John Iacomini, Laurie H. Glimcher, Mohamed H. Sayegh, M. Javeed Ansari
Journal: The Journal of Experimental Medicine (2008)

T-bet plays a crucial role in Th1 development. We investigated the role of T-bet in the development of allograft rejection in an established MHC class II–mismatched (bm12 into B6) model of chronic allograft vasculopathy (CAV). Intriguingly, and in contrast to IFN-γ−/− mice that are protected from CAV, T-bet−/− recipients develop markedly accelerated allograft rejection accompanied by early severe vascular inflammation and vasculopathy, and infiltration by predominantly IL-17–producing CD4 T cells. Concurrently, T-bet−/− mice exhibit a T helper type 1 (Th1)–deficient environment characterized by profound IFN-γ deficiency, a Th2 switch characterized by increased production of interleukin (IL) 4, IL-5, IL-10, and IL-13 cytokines, as well as increased production of the proinflammatory cytokines IL-6, IL-12p40, and IL-17. Neutralization of IL-17 inhibits accelerated allograft rejection and vasculopathy in T-bet−/− mice. Interestingly, CD4 but not CD8 T cell deficiency in T-bet−/− mice affords dramatic protection from vasculopathy and facilitates long-term graft acceptance. This is the first study establishing that in the absence of Th1-mediated alloimmune responses, CD4 Th17 cells mediate an aggressive proinflammatory response culminating in severe accelerated allograft rejection and vasculopathy. These results have important implications for the development of novel therapies to target this intractable problem in clinical solid organ transplantation.
Dangers of Steroids for Rheumatoid Arthritis
Authors: J. Forestier
Journal: BMJ (1964)

The interesting features of this case were:(1) that she lived to the age of 76; (2) that death was due to liver and not renal compli- cations; and (3) that the degree of portal compression by the huge cysts was sufficient to cause portal hypertension and subsequent bleeding oesophageal varices, without cir- -rhosis of the remaining compressed liver tissue.
Serum amyloid A protein concentration in progressive systemic sclerosis (scleroderma).
Authors: S R Brandwein, T A Medsger, M Skinner, J D Sipe, G P Rodnan, A S Cohen
Journal: Annals of the Rheumatic Diseases (1984)

Serum amyloid A protein (SAA) concentrations were determined in 62 patients with progressive systemic sclerosis (PSS). Forty-seven patients had normal or slightly elevated SAA levels (less than 1000 ng/ml = micrograms/l), while 15 patients had moderately to markedly elevated SAA levels, similar to those observed in active rheumatoid arthritis (RA) (greater than or equal to 1000 ng/ml = micrograms/l). Five patients with PSS had SAA levels corresponding to those observed in amyloidosis secondary to RA. High SAA was associated with more severe skin thickening and diminished cumulative survival at five years. The rarity of amyloidosis secondary to PSS is unlikely to be related to an intrinsic defect in SAA production.
Mortality from infectious pneumonia in metal workers: a comparison with deaths from asthma in occupations exposed to respiratory sensitisers
Authors: K T Palmer, P Cullinan, S Rice, T Brown, D Coggon
Journal: Thorax (2009)

National analyses of mortality in England and Wales have repeatedly shown excess deaths from pneumonia in welders. During 1979-90 the excess was attributable largely to deaths from lobar pneumonia and pneumonias other than bronchopneumonia, limited to men of working age and apparent in other occupations with exposure to metal fumes. The findings for 1991-2000 were assessed and compared with the mortality pattern from asthma in occupations exposed to known respiratory sensitisers.The Office of National Statistics supplied data on deaths by underlying cause among men aged 16-74 years in England and Wales during 1991-2000, including age and last held occupation. Data were abstracted on pneumonia for occupations with exposure to metal fumes and on asthma for occupations commonly reported to surveillance schemes as at risk of occupational asthma. The expected numbers of deaths were estimated by applying age-specific proportions of deaths by cause in the population to the total deaths by age in each occupational group. Observed and expected numbers were compared for each cause of death.Among men of working age in occupations with exposure to metal fumes there was excess mortality from pneumococcal and lobar pneumonia (54 deaths vs 27.3 expected) and from pneumonias other than bronchopneumonia (71 vs 52.4), but no excess from these causes at older ages or from bronchopneumonia at any age. The attributable mortality from metal fume exposure was 45.3 excess deaths compared with an estimated 62.6 deaths from occupational asthma.Exposure to metal fumes is a material cause of occupational mortality. The hazard deserves far more attention than it presently receives.
Physician Autonomy and Health Care Reform
Authors: Ezekiel J Emanuel, Steven D Pearson
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effect of Insulin in the Induction and Regression of Atherosclerosis in the Chick
Authors: JEREMIAH STAMLER, RUTH PICK, LOUIS N. KATZ
Journal: Circulation Research (1960)

Insulin administration to intact cockerels made atherosclerotic by the feeding of a cholesterol-oil-containing diet prevented regression of coronary atherosclerosis. Insulin administration during the induction of atherosclerosis had no effect on the development of lesions. In some experiments, insulin slightly inhibited estrogen-induced protection of the coronary arteries when the birds were on a high cholesterol-oil diet.
Depleted Dopamine in Gastric Cancer Tissues
Authors: Debanjan Chakroborty, Chandrani Sarkar, Rita Basu Mitra, Samir Banerjee, Partha Sarathi Dasgupta, Sujit Basu
Journal: Clinical Cancer Research (2004)

Abstract Purpose: It has been recently shown that the catecholamine neurotransmitter dopamine (DA) strongly and selectively inhibits vascular permeability factor/vascular endothelial growth factor (VPF/VEGF)-induced angiogenesis. Gastric cancer is highly angiogenic and is dependent on VEGF for its growth and progression. Because substantial amounts of DA present in normal stomach tissues has been implicated in several gastric functions, we therefore investigated the role, if any, of this neurotransmitter in the growth and progression of gastric cancer. Experimental Design: Initially, the status of DA and tyrosine hydroxylase, the rate-limiting enzyme required for DA synthesis, were determined in human gastric cancer tissues and in N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer tissues of rats. On the basis of our observation of inverse correlation between stomach DA and gastric cancer growth, we determined the effect of pharmacological dose of DA on the angiogenesis and growth of MNNG induced gastric cancer in rats and Hs746T human gastric cancer in nude mice. Results: DA and tyrosine hydroxylase were absent in both human and rat gastric cancer tissues. On the contrary, a low nontoxic pharmacological dose of DA significantly retarded tumor angiogenesis by inhibiting VEGFR-2 phosphorylation in tumor endothelial cells, which expressed DA D2 receptors. This action of DA was associated with the growth inhibition of both MNNG-induced rat malignant gastric tumors and xenotransplanted human gastric cancer in nude mice. Conclusions: Our study demonstrates that there is an inverse correlation between endogenous stomach DA and gastric cancer and indicates that DA already in clinical use for other purposes might have a role as an antiangiogenic agent in the treatment of gastric cancer.
Pericardial effusion associated with asbestos exposure
Authors: S. Trogrlic, P. A. Gevenois, M. Schroeven, P. De Vuyst
Journal: Thorax (1997)

The case history is presented of a 60 year old man who developed a pericardial effusion. Chest radiography showed pleural thickening and calcification. Pericardiotomy was performed and revealed nonspecific inflammatory lesions. Occupational exposure to asbestos and exclusion of other causes led to the diagnosis of benign asbestos pericardial effusion.
Ribonucleotide Reductase Messenger RNA Expression and Survival in Gemcitabine/Cisplatin-Treated Advanced Non-Small Cell Lung Cancer Patients
Authors: Rafael Rosell, Kathleen D. Danenberg, Vincente Alberola, Gerold Bepler, Jose Javier Sanchez, Carlos Camps, Mariano Provencio, Dolores Isla, Miquel Taron, Pilar Diz, Angel Artal
Journal: Clinical Cancer Research (2004)

Abstract Purpose: No chemotherapy regimen, including the widely used combination of gemcitabine/cisplatin, confers significantly improved survival over any other in metastatic non-small cell lung cancer (NSCLC); however, the selection of patients according to key genetic characteristics can help to tailor chemotherapy. Ribonucleotide reductase subunit M1 (RRM1) is involved in DNA synthesis and repair and in gemcitabine metabolism, and the excision repair cross-complementing group 1 (ERCC1) gene has been related to cisplatin activity. Experimental Design: Patients were part of a large randomized trial carried out from September 1998 to July 2000, comparing gemcitabine/cisplatin versus gemcitabine/cisplatin/vinorelbine versus gemcitabine/vinorelbine followed by vinorelbine/ifosfamide. We analyzed RRM1 and ERCC1 mRNA expression in paraffin-embedded samples obtained from bronchoscopy by real-time quantitative reverse transcription-PCR. Results were correlated with survival using the Kaplan-Meier method. Results: A total of 100 patients were assessed. There was a strong correlation between RRM1 and ERCC1 mRNA expression levels (Spearman r = 0.410; P &amp;lt; 0.001). In the gemcitabine/cisplatin arm, patients with low RRM1 mRNA expression levels had significantly longer median survival than those with high levels [13.7 versus 3.6 months; 95% confidence interval (CI), 9.6–17.8 months; P = 0.009]. Median survival was also significantly longer among patients with low mRNA expression levels of both RRM1 and ERCC1 (not reached), than among those with high levels of both genes (6.8 months; 95% CI, 2.6–11.1 months; P = 0.016). Conclusions: RRM1 mRNA expression is a crucial predictive marker of survival in gemcitabine/cisplatin-treated patients. Genetic testing of RRM1 mRNA expression levels can and should be used to personalize chemotherapy.
FGF-2 protects cardiomyocytes from doxorubicin damage via protein kinase C-dependent effects on efflux transporters
Authors: Jie Wang, Mark W. Nachtigal, Elissavet Kardami, Peter A. Cattini
Journal: Cardiovascular Research (2013)

The anti-cancer anthracycline doxorubicin (DOX) increases the risk of cardiac damage, indicating a need to protect the heart and still allow the benefits of drug treatment. Fibroblast growth factor-2 (FGF-2) is cardioprotective against ischaemia–reperfusion injury. Our aim is to investigate: (i) the ability of FGF-2 to protect against DOX-induced cardiomyocyte damage and (ii) the contribution of efflux drug transport to any increase in injury-resistance. Neonatal rat cardiomyocyte damage was assessed by measuring cell death markers and lactate dehydrogenase (LDH) activity in the culture medium. LDH activity was increased significantly after incubation with 0.5 μM DOX for 24 h in the absence but not presence of 10 nM FGF-2; this beneficial effect of FGF-2 was blocked by tyrosine kinase (FGF) receptor inhibition. An increase in efflux drug transporter RNA levels was also detected after FGF-2 treatment in the presence of DOX. The beneficial effect of FGF-2 against cell damage and increased transporter RNA levels were blunted with protein kinase C (PKC) inhibition. Finally, FGF-2 stimulated efflux transport of calcein and DOX, and treatment with efflux transporter inhibitors significantly attenuated the protective effect of FGF-2 from DOX-induced injury. Administered FGF-2 increases resistance to DOX-induced cardiomyocyte damage, by a mechanism dependent on PKC as well as regulation of efflux transporter production and/or function.
<i>HFE H63D</i> Polymorphism as a Modifier of the Effect of Cumulative Lead Exposure on Pulse Pressure: The Normative Aging Study
Authors: Aimin Zhang, Sung Kyun Park, Robert O. Wright, Marc G. Weisskopf, Bhramar Mukherjee, Huiling Nie, David Sparrow, Howard Hu
Journal: Environmental Health Perspectives (2010)

BackgroundCumulative lead exposure is associated with a widened pulse pressure (PP; the difference between systolic and diastolic blood pressure), a marker of arterial stiffness and a predictor of cardiovascular disease. Polymorphisms in the hemochromatosis gene (HFE) have been shown to modify the impact of cumulative lead exposure on measures of adult cognition and cardiac function.ObjectivesWe examined whether the HFE mutations modify the impact of lead on PP in community-dwelling older men.MethodsWe examined 619 participants with a total of 1,148 observations of PP from a substudy of bone lead levels (a measure of cumulative exposure, measured by in vivo K-shell X-ray fluorescence) and health in the Normative Aging Study between 1991 and 2001. Linear mixed-effects regression models with random intercepts were constructed.ResultsOf the 619 subjects, 138 and 72 carried the HFE H63D and C282Y variants, respectively. After adjusting for age; education; alcohol intake; smoking; daily intakes of calcium, sodium, and potassium; total calories; family history of hypertension; diabetes; height; heart rate; high-density lipoprotein (HDL); total cholesterol:HDL ratio; and waist circumference, baseline bone lead levels were associated with steeper increases in PP in men with at least one H63D allele (p-interaction = 0.03 for tibia and 0.02 for patella) compared with men with only the wild types or C282Y variant.ConclusionsThe HFE H63D polymorphism, but not the C282Y mutation, appears to enhance susceptibility to the deleterious impact of cumulative lead on PP, possibly via prooxidative or pro-inflammatory mechanisms.