tbuckley/cabot-search huggingface dataset:
Accelerated Mitochondrial Adenosine Diphosphate/Adenosine Triphosphate Transport Improves Hypertension-Induced Heart Disease
Authors: Thomas Walther, Carsten Tschöpe, Anja Sterner-Kock, Dirk Westermann, Silvia Heringer-Walther, Alexander Riad, Alen Nikolic, Yong Wang, Linda Ebermann, Wolf-Eberhard Siems, Michael Bader, Mehdi Shakibaei, Heinz-Peter Schultheiss, Andrea Dörner
Journal: Circulation (2007)

Strong evidence suggests that mitochondrial malfunction, which leads to disturbed energy metabolism and stimulated apoptosis, is a linchpin in the induction and manifestation of cardiac failure. An adequate exchange of ATP and ADP over the inner mitochondrial membrane by the adenine nucleotide translocase (ANT) is thereby essential to guarantee the cellular energy supply.To explore the effect of an ameliorated mitochondrial ATP/ADP transportation on cardiac dysfunction, we generated transgenic rats overexpressing ANT1 in the heart (ANT rats) and crossed them with renin-overexpressing rats (REN rats) suffering from hypertension-induced cardiac insufficiency. Cardiac-specific ANT1 overexpression resulted in a higher ATP/ADP transportation and elevated activities of respiratory chain complexes. Increased ANT activity in double-transgenic (ANT/REN) animals did not influence excessive hypertension seen in REN rats. Hypertension-induced cardiac hypertrophy in the REN rats was prevented by parallel ANT1 overexpression, however, and left ventricular function remarkably improved. The ANT1 overexpression led to a reduction in fibrosis and an improvement in cardiac tissue architecture. Consequently, the survival rate of ANT/REN rats was enhanced. Further investigations into the cardioprotective mechanism of ANT1 overexpression revealed improved mitochondrial structure and function and significantly reduced apoptosis in ANT/REN rats, shown by lowered cytosolic/mitochondrial cytochrome c ratio, reduced caspase 3 level, and prevented DNA degradation.Myocardial ANT1 overexpression protects against hypertension-induced cardiac pathology. Thus, the improvement in mitochondrial function may be a basic principle for new strategies in treating heart disease.
Parabiotic Resuscitation in Profound Cardiovascular Failure
Authors: Lester R. Bryant
Journal: JAMA (1967)

Irreversibles an enigma in experimental animals and in man. Much work has been done in an effort to elucidate the pathophysiological changes which characterize the state of "irreversibility" so that specific therapy may be directed at these disturbances. Even though irreversible shock cannot be defined as precisely in man as in the dog, it seems likely that the basic metabolic consequences of prolonged shock are similar in both species. The differences in the pathological manifestations of shock between man and experimental animals seem related to differences in susceptibility of various organs to the hemodynamic changes of shock. Lillehei<sup>1</sup>has proposed a unified concept in which the stage of irreversibility, whether induced by hemorrhage, bacterial endotoxins, or myocardial failure, is characterized by loss of tone in precapillary arterial sphincters while postcapillary sphincters remain constricted. The result is a progressive loss of plasma from the vascular system, stagnant anoxia and congestion
A Simplified Benzidine Test
Authors: A. Hughes
Journal: BMJ (1952)

Hypertension and Size of Heart Chest radiography was carried out in 332 subjects (143 males and 189 females).There was no significant associa- tion between the systolic or diastolic blood pressure and the,size of the heart estimated from a chest radiograph taken at a distance of 6 feet (1.8 metres).Two independent criteria were used: First, the opinion of the radiologist (J.L. A. G.) on inspecion of the film, and, secondly, the cardio-thoracic ratio (the maximtum width of the heart shadow divided by the externlal width of the bony thorax at that level).Application of the ,X2 test to the results, shown in Table IX, indicated that enlargement of the heart was not diagnosed by the radiologist significantly more often in those with TABLE IX.-Size of Hearst (A.ssessed by Radiologist) and Blood Pressule Systolic Diastolic 0-159 I 160- 0-99 100-No. of men radiographed 62 81 107 36 No. with enlarged hearts I.. .. 11(17-7%/O) 20 (24-7%°) 21 (19-6%) 10 (27-7%) No. of women radiographed .. .. 46 143 98 91 No. with enlarged hearts .. .. 11(23*9%) 35 ( 24.5%) 24 (245%) 22 (24 2%) high blood pressures than in those with low ones.Also the correlation coefficients between the cardio-thoracic ratios and both systolic and diastolic blood pressures were not significant at the 5%level.While the numbers are too small to justify a firm con- clusion they suggest that hypertension by itself is not an important cause of cardiac enlargement in the elderly. Hypertension and FitnessAt the end of the examination the subject was asked whether he considered himself fit, moderately fit, or unfit (Table X).The proportion of those in the high-blood- pressure and low-blood-pressure groups who considered themselves fit did not differ significantly.TABLE X.-Siubjects' Self-assessment of Fitness bY Blood Pr-essuri-e Systolic Diastolic * 0-179 180+ 0-99 I 004+ No. of males in group.. 120 67 132 53 No. "fit" .. .. 75 (62 5%) 38 (57%) 80 (60 6%) l33 (62%) No. of females in group 131 138 140 129 No. "fit" .. .. 67 (57%) 60 (43.5%) 70 (50%) -57 (44%) * In two cases diastolic pressure not recorded.The X test showed that the differences were not significant at the 5',)%0 level of probability.It seems, therefore, that in this age group there is little association between feeling of fitness and the height of the blood pressure.A further assessment of the relation be- tween hypertension and general health was made by exam- ining the relationship between the blood pressure and the activity of the subject grouped under four headings: (a) unlimited outdoor activity; (b) limited outdoor activity; (c) confined to the house; and (d) bedfast.There was no correlation between degree of activity assessed in this way and systolic or diastolic blood pressure.Correlation Coefficients Betweeni Activity and Blood Pressure Females Systolic B.P. .. r=0-093 Males f Systolic B.P. .. r==0-052 (269) ODiastolic ,. .r--0109 (186) aDiastolic ,, .. r-007 Summary Clinical examination was made of 192 men and 284 women over pensionable age and living at home in Sheffield.Chest radiography was carried out in 332 who came to hospital.forthe purpose.
Tumor Necrosis Factor–α Overexpression in Lung Disease
Authors: Lennart K. A. Lundblad, John Thompson-Figueroa, Timothy Leclair, Michael J. Sullivan, Matthew E. Poynter, Charles G. Irvin, Jason H. T. Bates
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Tumor necrosis factor alpha (TNF-alpha) has been implicated as a key cytokine in many inflammatory lung diseases. These effects are currently unclear, because a transgenic mouse overexpressing TNF-alpha in the lung has been shown in separate studies to produce elements of both emphysema and pulmonary fibrosis.We sought to elucidate the phenotypic effects of TNF-alpha overexpression in a mouse model.We established the phenotype by measuring lung impedance and thoracic gas volume, and using micro-computed tomography and histology.We found that airways resistance in this mouse was not different to control mice, but that lung tissue dampening, elastance, and hysteresivity were significantly elevated. Major heterogeneous abnormalities of the parenchyma were also apparent in histologic sections and in micro-computed tomography images of the lung. These changes included airspace enlargement, loss of small airspaces, increased collagen, and thickened pleural septa. We also found significant increases in lung and chest cavity volumes in the TNF-alpha-overexpressing mice.We conclude that TNF-alpha overexpression causes pathologic changes consistent with both emphysema and pulmonary fibrosis combined with a general lung inflammation, and consequently does not model any single human disease. Our study thus confirms the pleiotropic effects of TNF-alpha, which has been implicated in multiple inflammatory disorders, and underscores the necessity of using a wide range of investigative techniques to link gene expression and phenotype in animal models of disease.
A New Clinical Syndrome Producing Hypertension— Arteriovenous Fistula of The Kidney
Authors: Charles H. Scheifley
Journal: JAMA (1960)

It is the purpose of this paper to call attention to a renal-vascular syndrome which should be added to the group of known and reversible causes of arterial hypertension, cardiac enlargement, and heart failure. This clinical entity is arteriovenous fistula of the kidney. Although this subject was recently documented in an inclusive monographic type of report,<sup>1</sup>the fact that it constitutes a clear-cut clinical entity which is virtually diagnostic was neither mentioned nor emphasized. It is hoped that this brief summary will correct this deficiency. The discussion which constitutes the remainder of this paper is the result of a careful analysis of all the cases which have been reported in the literature to date. Twelve separate reports of this condition were found in the literature, to which we have added our own three carefully studied cases.<sup>1</sup> <h3>Clinical Features</h3> Four basic elements constitute the symptomcomplex which outlines the distinctive
Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial
Authors: Piero Ruggenenti, Annalisa Perna, Giacomina Loriga, Maria Ganeva, Bogdan Ene-Iordache, Marta Turturro, Maria Lesti, Elena Perticucci, Ivan Nediyalkov Chakarski, Daniela Leonardis, Giovanni Garini, Adalberto Sessa, Carlo Basile, Mirella Alpa, Renzo Scanziani, Gianbattista Sorba, Carmine Zoccali, Giuseppe Remuzzi
Journal: The Lancet (2005)
Abstract 4124: Pre-treatment complement system serum protein levels predict pathological response to neoadjuvant chemoradiotherapy for esophageal cancer
Authors: Stephen G. Maher, Dermot T. McDowell, Sinead A. Murphy, Ben C. Collins, Cian Muldoon, William M. Gallagher, John V. Reynolds
Journal: Cancer Research (2011)

Abstract Introduction: Esophageal cancer has one of the worst prognosis of all cancers, and its incidence is increasing rapidly in the Western world. The standard of care for patients with esophageal cancer involves neoadjuvant chemoradiotherapy (neo-CRT) followed by surgery. Unfortunately, only ∼30% of esophageal cancer patients respond to neo-CRT. The aim of this study was to analyse the serum proteome early into neo-CRT to reveal biomarkers indicative of response to therapy. Methods: 31 esophageal cancer patients received a standard neo-CRT regimen. Pathological response to therapy was assessed using the Mandard Tumour Regression Grade system. Serum was collected at pre-treatment, 24 h and 48 h timepoints into treatment. Albumin/IgG-depleted serum samples were analyzed using SELDI-TOF-MS. Protein/peptide expression difference mapping was performed and the data applied to the EPO-KB database. Subsequently, high-scoring candidates were assayed by ELISA. A leave-one-out cross validation (LOOCV) predictive algorithm was employed to assess the ability of candidate biomarkers to correctly predict therapeutic outcome. Results: 16 patients had a poor response to therapy, while 15 had a good response. On CM10 chips, 9 protein peaks were significantly different between the two treatment response groups, some at baseline, others at 24 h and 48 h into neo-CRT. SELDI spectral peaks m/z_8617.685 and m/z_8928.422 were identified as the complement proteins C4a and C3a, respectively, via the EPO-KB. ELISA revealed significantly higher pre-treatment levels of C4a and C3a in serum from poor versus good responders. Subdivision of the response groups by TRG indicated an inverse correlation between levels of C4a and C3a and pathological response to neo-CRT. In a pre-treatment setting, LOOCV analysis revealed that these two serum proteins could predict patient response to neo-CRT with a sensitivity and specificity of 78.6% and 83.3%, respectively. Conclusion: In a relatively non-invasive approach, this study has identified that pre-treatment levels of serum C4a and C3a are potential pre-treatment biomarkers predicting response to neo-CRT for esophageal cancer. Additional serum proteins are being validated to further improve the sensitivity and specificity of predicting esophageal patient response to treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4124. doi:10.1158/1538-7445.AM2011-4124
Scientist concludes that easy stem cell production published in Nature "does not work"
Authors: N. Hawkes
Journal: BMJ (2014)

A Hong Kong scientist who has tried to replicate a supposedly easy way to generate stem cells has been forced to conclude that the method does not work.

Kenneth Lee and colleagues at the Chinese University of Hong Kong were among the scientific groups that actively followed up what would have been, in his words, “a major game changer in regenerative medicine.” 

This was the controversial claim published in Nature by Haruko Obokata and colleagues from the RIKEN Centre for Developmental Biology in Kobe, Japan, that subjecting mouse cells to immersion in a bath of warm acid restored them to a pluripotent state—from which, in principle, they could be used to create a …
Characterisation of oxidative injury to an intestinal cell line (HT-29) by hydrogen peroxide.
Authors: A J Watson, J N Askew, G I Sandle
Journal: Gut (1994)

Reactive oxygen metabolites have been implicated in causing epithelial cell injury in colonic inflammation. A model of oxidant injury in intestinal epithelial cells has been developed in which HT-29-18-C1 cells are injured with graded concentrations of hydrogen peroxide and characterised by the MTT test. The MTT test was validated as a cytotoxicity assay and has a similar sensitivity to hydrogen peroxide induced injury as the assay of intracellular adenosine triphosphate. Exposure to a range of hydrogen peroxide concentrations (0.05-20 mM) for varying duration (5-120 min) showed that injury was dependent on time and concentration. The median lethal dose (LD50) for one hour exposure to hydrogen peroxide was approximately 0.1 mM. Injury from hydrogen peroxide was only partially reversible as determined by the MTT test and assay of cellular proliferation by crystal violet staining. There was an exponential loss of hydrogen peroxide when incubated with HT-29-18-C1 cells (t1/2 35 min). Experiments with 0.5 mg/ml aminotriazole and 0.5-2 mM buthionine sulphoximine suggested hydrogen peroxide breakdown was predominantly caused by catalase rather than glutathione peroxidase. Injury resulting from 1 mM hydrogen peroxide could be reduced by either coincubation of cells with 1,10-phenanthroline, an Fe2+ chelator, or preincubation with deferoxamine, and Fe3+ chelator, suggesting the participation of Fe2+ and Fe3+ in hydrogen peroxide induced injury. In conclusion, hydrogen peroxide induces injury in HT-29-18-C1 cells both directly and by generation of the hydroxyl radical.
Book Review Paying the Doctor: Health policy and physician reimbursement Edited by Jonathan D. Moreno. 194 pp. New York, Auburn House, 1991. $39.95. Free to Be Foolish: Politics and health promotion in the United States and Great Britain By Howard M. Leichter. 281 pp. Princeton, N.J., Princeton University Press, 1991. $35.
Authors: Eli Ginzberg
Journal: New England Journal of Medicine (1991)
Direct Assessment of Drug Penetration into Tissue Using a Novel Application of Three-Dimensional Cell Culture
Authors: Alastair H. Kyle, Lynsey A. Huxham, Aaron S. J. Chiam, David H. Sim, Andrew I. Minchinton
Journal: Cancer Research (2004)

Abstract The failure of many anticancer drugs to control growth of solid cancers may stem in part from inadequate delivery to tumor regions distant from vasculature. Although the identification of new anticancer drug targets has led to the development of many new drug candidates, there is a lack of methodology for identifying drugs that adequately penetrate tumor tissue. We have developed a novel multilayered cell culture-based assay, which detects the penetration of anticancer drugs based on their effect within tissue. Drug exposures are made over 1 hour to one side of a disk of tissue ∼150-μm thick, with the other side temporarily closed off, and penetration is then assessed 1–3 days later via bromodeoxyuridine-based detection of S-phase cells. Using this assay, the tissue distribution of a selection of anthracycline analogues was assessed. At clinically relevant exposures, none of the agents were able to affect cells on the far side of the culture at levels approaching that seen on the near (exposed) side. Doxorubicin and epirubicin exhibited ∼10-fold decreases in the drug exposure seen by the cells on the far side relative to those on the near side of the cultures, whereas for daunorubicin and mitoxantrone, ∼30-fold and &amp;gt;30-fold decreases were observed respectively. Results were consistent with the observed gradients in drug-derived fluorescence of doxorubicin, epirubicin, and daunorubicin. This model could be applied as a simple anticancer drug development screen to discover drugs that exhibit desirable penetration properties.
Nigerians to sue US drug company over meningitis treatment
Authors: C. Kovac
Journal: BMJ (2001)

In what is reportedly the first such legal action in the United States, 30 families from Nigeria are suing the US based drug manufacturer Pfizer Pharmaceuticals in a federal court in New York for allegedly carrying out medical experiments on the children of foreign citizens without consent.

The move marks the latest development in a long saga about whether Pfizer used a new drug without official approval during a meningitis epidemic in Nigeria five years ago. An inquiry was set up by the Nigerian health minister, Tim Menakaya, in January this year into the allegations ( BMJ 2001;322:194).

According to the suit, during a meningitis epidemic in 1996 …
The Apothecaries' Society, the Profession, and the Public
Authors: None Green, None Pridham
Journal: BMJ (1879)

Intravenous administration of apoA-I complexed with phospholipid has been shown to rapidly reduce plaque size in both animal models and in humans. Short synthetic amphipathic peptides can mimic the anti-atherogenic properties of apoA-I and have been proposed as alternative therapeutic agents. In this study, we investigated the atheroprotective effect of the 5A peptide, a bi-helical amphipathic peptide that specifically effluxes cholesterol from cells by the ABCA1 transporter. 5A stimulated a 3.5-fold increase in ABCA1 mediated efflux from cells and a further 2.5-fold increase after complexing it with phospholipid (5A:POPC [1:7 mol/mol]). 5A:POPC but not free 5A was also found to promote cholesterol efflux by ABCG1. When incubated with human serum, 5A-POPC primarily bound to HDL but also to LDL and promoted the transfer of cholesterol from LDL to HDL. 24 hours following IV injection of 5A-POPC (30 mg/kg) into apoE-KO mice, both the cholesterol (181%) and phospholipid (219%) content of HDL significantly increased. By an in vivo cholesterol isotope dilution study and by monitoring the flux of cholesterol from radiolabeled macrophages to stool, 5A-POPC treatment was observed to increase reverse cholesterol transport. In three separate studies, 5A when complexed with various phospholipids reduced aortic plaque surface area by 29-53% (n=8 per group, p&lt;0.02) in apoE-KO mice. No signs of toxicity from the treatment were observed during these studies. In summary, 5A promotes cholesterol efflux both in vitro and in vivo and reduces atherosclerosis in apoE-KO mice, indicating that it may be a useful alternative to apoA-I for HDL therapy.
RECURRENT TETANUS SUCCESSFULLY TREATED WITH AZOSULFAMIDE
Authors: Frederick Lemere
Journal: JAMA (1941)

The following case is presented because of its significance to wartime medicine. Tetanus is comparatively rare in civil life, and there has been little opportunity to observe the effect of the new sulfonamide preparations in this disease. In the case here reported 110,000 units of tetanus antitoxin was given for the original attack, with recurrence eighteen days later. The second attack was successfully treated with azosulfamide. <h3>REPORT OF CASE</h3><h3>History.—</h3> A youth aged 19, a mill worker, seen with Dr. E. M. Chew in consultation, was admitted to the Ballard General Hospital July 29, 1940 with headache, nausea, vomiting, numbness of the hands and chin, abdominal pain, inability to void, mild delirium and tetanic convulsions. The mode of infection was uncertain. A week before he had chafed his thighs while riding a horse and two or three weeks before had bruised a toe and injured a finger while working.
Effects of Iproniazid in Depressive Syndromes
Authors: E. D. West, P. J. Dally
Journal: BMJ (1959)

POSTUREMeDIBRnm L 1491 dystonia.It is perhaps too early to draw any conclusions from this, but the facts just quoted may suggest that extrapyramidal rigidity and disturbances of posture are due to abnormal impulses descending from above the brain-stem level.