tbuckley/cabot-search huggingface dataset:
Pressure Overload Induces Severe Hypertrophy in Mice Treated With Cyclosporine, an Inhibitor of Calcineurin
Authors: Bo Ding, Robert L. Price, Thomas K. Borg, Ellen O. Weinberg, Philip F. Halloran, Beverly H. Lorell
Journal: Circulation Research (1999)

Abstract —Cardiac hypertrophy is the fundamental adaptation of the adult heart to mechanical load. Recent work has shown that inhibition of calcineurin activity with cyclosporine suppresses the development of hypertrophy in calcineurin transgenic mice and in in vitro systems of neonatal rat cardiocytes stimulated with peptide growth factors. To test the hypothesis that the calcineurin signaling pathway is critical for load-induced hypertrophy in vivo, we examined the effects of cyclosporine treatment on left ventricular hypertrophy induced by experimental ascending aortic stenosis for 4 weeks in mice. Left ventricular systolic pressure was elevated to a similar level in aortic stenosis mice that were treated with cyclosporine versus no drug. Left ventricular mass and myocyte size were similar in treated and untreated aortic stenosis animals and significantly greater than control animals, showing that cyclosporine treatment does not suppress hypertrophic growth. Both treated and untreated animals showed increased left ventricular expression of the load-sensitive gene atrial natriuretic factor. Calcineurin activity was measured in the left ventricle and the spleen from control mice and aortic stenosis mice treated with cyclosporine versus no drug. Levels of calcineurin activity were similar in the spleens of control and untreated aortic stenosis mice. However, calcineurin activity was severely depressed in left ventricular tissue of untreated aortic stenosis mice compared with control mice and was further reduced by cyclosporine treatment. Thus, pathological hypertrophy and cardiac-restricted gene expression induced by pressure overload in vivo are not suppressed by treatment with cyclosporine and do not appear to depend on the elevation of left ventricular calcineurin activity.
Darier's disease: an immunohistochemical study using monoclonal antibodies to human cytokeratins
Authors: S.M. BURGE, D.A. FENTON, R.P.R. DAWBER, I.M. LEIGH
Journal: British Journal of Dermatology (1988)

The pathogenesis of Darier's disease was investigated by immunohistochemical staining of skin biopsies from involved and uninvolved skin in 14 patients, using monoclonal antibodies specific for keratins expressed in simple epithelia, stratified squamous epithelia and during skin specific differentiation as well as keratins expressed in mucosa and some benign epidermal hyperproliferative states. Uninvolved perilesional skin from Darier's patients showed a normal profile of keratin expression, whereas in lesional skin there was apparent delay in the expression of the suprabasal skin specific keratins. Suprabasal keratins were not detected in basal cells, thus there was no true premature keratinization. The presence of hyperproliferative keratins was restricted to suprabasal cells in lesional skin. Four patients were receiving treatment with ctretinate at the time of biopsy, but results in these patients did not differ from patients using topical treatments. Etretinate did not influence the profile of keratin expression in uninvolved or involved skin. The expression of type VII collagen was examined and was normal throughout uninvolved and iL‐sHiiitil skin in Darier's disease.
Activity Of Carbonic Anhydrase In Erythrocytes Of Patients Suffering From Pulmonary Alveolar Microlithiasis
Authors: Alfonso Esguerra-Fajardo
Journal: JAMA (1960)

Pulmonary alveolar microlithiasis is a rare disease, there being only 50 or 60 cases described in the medical literature. Since, as a rule, persons with this condition are completely asymptomatic, the diagnosis is usually made after a routine radiographic examination of the thorax. The disease is characterized by the presence of microliths of calcium carbonate and phosphate free in the pulmonary alveoli. A roentgenogram of such lungs usually shows numerous small calcifications about the size of grains of sand distributed through all of the bronchial ramifications. The etiology of microlithiasis is unknown, but it seems reasonable to assume that the disease results from a disturbance in the metabolism of carbon dioxide. As a result, the medium at the surface of the alveoli becomes more alkaline, which favors the precipitation of the microliths. The most comprehensive review of this disease is that written by Sosman and others<sup>1</sup>in 1957. These
Uptake and Elimination of Brevetoxin in Blood of Striped Mullet ( <i>Mugil cephalus</i> ) after Aqueous Exposure to <i>Karenia brevis</i>
Authors: Ricky T. Woofter, Kirsten Brendtro, John S. Ramsdell
Journal: Environmental Health Perspectives (2004)

There is a critical need to simply and reliably monitor brevetoxins routinely in the blood of humans and aquatic animals. We used striped mullet as laboratory test animals to better define the uptake and elimination kinetics of brevetoxin during an aqueous exposure to the brevetoxin-producing dinoflagellate Karenia brevis. Striped mullet were first exposed to sublethal densities of K. brevis (approximately 250,000 cells/L) for 1, 4, 8, 12, and 24 hr. No mortality was observed in the aquaria, and at each time point blood samples were taken and applied to blood collection cards for brevetoxin analysis using radioimmunoassay (RIA). The RIA indicated that blood levels of brevetoxin (PbTx-3) increased to values significantly different from that of the controls at all five time points during exposure (p < 0.05). Striped mullet were then exposed to a K. brevis culture with a known brevetoxin concentration of 0.5 ng/mL. Even after exposures at a low brevetoxin concentration, RIA was able to detect 2.25 +/- 0.62 ng/mL PbTx-3 equivalents in the blood of the mullet at 8 hr of exposure. When exposed to higher brevetoxin concentrations (3.5 and 5.4 ng/mL), blood brevetoxin increased to peak levels at 12 hr and then reached equilibrium after 24 hr in the continued presence of K. brevis. During this time of equilibrium, the mullet maintained brevetoxins with a blood:water coefficient of 2.2. To define the elimination of brevetoxin, striped mullet were next exposed for 8-10 hr and then transferred to fresh seawater containing no K. brevis for up to 116 hr. Blood brevetoxin levels remained elevated and decreased only by 50% 116 hr after transfer. The rate of elimination fit best to a two-phase exponential decay with a biologic half-life of 12 and 266 hr. This study, using RIA in conjunction with blood collection cards, demonstrates an effective means to monitor blood brevetoxin levels in finfish and provides a foundation to characterize biologically relevant levels of brevetoxin in other species impacted by red tide events.
Transduction Efficiency and Immune Response Associated With the Administration of AAV8 Vector Into Dog Skeletal Muscle
Authors: Sachiko Ohshima, Jin-Hong Shin, Katsutoshi Yuasa, Akiyo Nishiyama, Junichi Kira, Takashi Okada, Shin'ichi Takeda
Journal: Molecular Therapy (2008)

Recombinant adeno-associated virus (rAAV)-mediated gene transfer is an attractive approach to the treatment of Duchenne muscular dystrophy (DMD). We investigated the muscle transduction profiles and immune responses associated with the administration of rAAV2 and rAAV8 in normal and canine X-linked muscular dystrophy in Japan (CXMD(J)) dogs. rAAV2 or rAAV8 encoding the lacZ gene was injected into the skeletal muscles of normal dogs. Two weeks after the injection, we detected a larger number of beta-galactosidase-positive fibers in rAAV8-transduced canine skeletal muscle than in rAAV2-transduced muscle. Although immunohistochemical analysis using anti-CD4 and anti-CD8 antibodies revealed less T-cell response to rAAV8 than to rAAV2, beta-galactosidase expression in rAAV8-injected muscle lasted for <4 weeks with intramuscular transduction. Canine bone marrow-derived dendritic cells (DCs) were activated by both rAAV2 and rAAV8, implying that innate immunity might be involved in both cases. Intravenous administration of rAAV8-lacZ into the hind limb in normal dogs and rAAV8-microdystrophin into the hind limb in CXMD(J) dogs resulted in improved transgene expression in the skeletal muscles lasting over a period of 8 weeks, but with a declining trend. The limb perfusion transduction protocol with adequate immune modulation would further enhance the rAAV8-mediated transduction strategy and lead to therapeutic benefits in DMD gene therapy.
A QUANTITATIVE STUDY OF CHLORPROMAZINE AND ITS SULFOXIDES IN THE URINE OF PSYCHOTIC PATIENTS
Authors: CHIEN LI HUANG, ALBERT A. KURLAND
Journal: American Journal of Psychiatry (1961)

A group of 7 chronically ill, male, schizophrenic patients living on the same ward over a period of at least a year were studied. Spectrophotometric measurements of approximately 3,600 urine specimens were performed in order to determine the excretion pattern of free chlorpromazine and the 3 chlorpromazine sulfoxides which were identified on paper chromatograms. The average excretion of free chlorpromazine and its sulfoxides combined during the period of continuous medication with chlorpromazine at dosage of 100 mg. to 400 mg. t.i.d. ranged from 1.31 to 20.54% of the administered dose. Of this, free chlorpromazine was usually found to be less than 1%, while the sulfoxides ranged from 1 to 18% of the administered dose. The average ratio of free chlorpromazine to its sulfoxides was found to be approximately 1 to 16. After the medication was stopped, free chlorpromazine and its sulfoxides disappeared from the urine within 5 days.
Effect of atropine on sputum production.
Authors: M T Lopez-Vidriero, J Costello, T J Clark, I Das, E E Keal, L Reid
Journal: Thorax (1975)

<h3>Abstract</h3> Alpha is one of the most prominent rhythms (7.5–12.5 Hz) detected in electroencephalography (EEG) during wakeful relaxation with closed eyes. In response to elevated ambient acetylcholine levels, a subclass of thalamic pacemaker cells generate alpha. This rhythm is intrinsic to the cell and is robustly orchestrated by an interplay of hyperpolarization activated cyclic nucleotide gated channels(HCN) and calcium-ion channels. It has been shown that decreased expression of HCN channels is correlated to Alzheimer9s Diseased (AD). In early stages of AD, alpha is known to be down-regulated and lowered in coherence. We use this well characterized and quantified rhythm to understand the changes in ion channel properties that lead to disruption of alpha as seen in AD in a biophysically detailed network model of the thalamo-cortical circuit that generates the alpha-rhythm. Our computational model allows us to explore the causal links between alpha rhythms, HCN channels and amyloid-beta aggregation. The most commonly used drugs(acetylcholinesterase inhibitors) in AD increase the duration and level of acetylcholine and provide temporary symptomatic relief in some cases. Our simulations show how increasing acetylcholine can provide rescue for a small range of aberrant HCN expression. We hypothesize that reduced alpha rhythm frequency and coherence is a result of down-regulated HCN expression, rather then compromised cholinergic modulation(as is currently thought). The model predicts that lowering of the alpha-rhythm can modify the network activity in the thalamo-cortical circuit and lead to an increase in the inhibitory drive to the thalamus.
THE EFFECT OF ANESTHETICS ON HEPATIC FUNCTION
Authors: SANFORD M. ROSENTHAL
Journal: JAMA (1928)

Experimental studies on liver function are often carried out under anesthesia, although it is being increasingly recognized that anesthetics modify physiologic processes; the pharmacologist has also shown that they alter the response of the body to many drugs. Death at times occurs during operative procedures on patients with severe liver disease; the effect of anesthetics on a diseased liver may play an important role in such fatalities.  For these reasons we have undertaken to study the effect of various anesthetics on the liver, as indicated by bile pigment disturbances and by the bromsulphalein test for hepatic function. The changes which anesthetics produce on the liver, however, have a more general interest in that this impaired function is only a reflection of the widespread depression of cell activity resulting from certain anesthetics; analogous changes are undoubtedly produced in most other organs.  The tests based on pigment metabolism which we have employed
Use of a cardiac occluder for closure of a complex gastric leak after bariatric surgery
Authors: Reiner Wiest, Radu Tutuian, Bernhard Meier, Philipp Nett
Journal: Endoscopy (2014)

Gastric leakage after sleeve gastrectomy is reported in up to 9 % of cases [1]. Endoscopic measures to manage such complications include insertion of self-expandable metal stents, and application of endoclips or over-the-scope clips [1]. Interventional cardiologists use specialist Amplatzer Occluders (St. Jude Medical, Plymouth, Minnesota, United States) for closure of patent foramen ovale, atrial septal defects, or ventricular septal defects (VSDs) [2]. The Amplatzer Occluder is a self-expandable double-disc device made from a nitinol wire mesh. Dacron polyester patches are sewn into each disc and the connecting waist in order to enhance endocardialization of the device. The device was specifically designed for the muscular VSD, and features a neck that is 5 – 10 mm in length, commensurate with the defect, and a slightly larger retention disc on the distal (left) side. This report describes the use of such a device to close a complex gastric leak after bariatric surgery.
Effect of adenosine1-receptor blockade on renin release from rabbit isolated perfused juxtaglomerular apparatus.
Authors: H Weihprecht, J N Lorenz, J Schnermann, O Skøtt, J P Briggs
Journal: Journal of Clinical Investigation (1990)

Adenosine has been proposed to act within the juxtaglomerular apparatus (JGA) as a mediator of the inhibition of renin secretion produced by a high NaCl concentration at the macula densa. To test this hypothesis, we studied the effects of the adenosine1 (A1)-receptor blocker 8-cyclopentyl-1,3-dipropylxanthine (CPX) on renin release from single isolated rabbit JGAs with macula densa perfused. The A1-receptor agonist, N6-cyclohexyladenosine (CHA), applied in the bathing solution at 10(-7) M, was found to inhibit renin secretion, an effect that was completely blocked by adding CPX (10(-5) M) to the bath. Applied to the lumen, 10(-5) M CPX produced a modest stimulation of renin secretion rates suppressed by a high NaCl concentration at the macula densa (P less than 0.05). The effect of changing luminal NaCl concentration on renin secretion rate was examined in the presence of CPX (10(-7) and 10(-5) M) in the bathing solution and in vehicle control experiments. The control response to increasing luminal NaCl concentration was a marked suppression of renin secretion, that was maintained as long as luminal NaCl concentration was high and was promptly reversible when concentration was lowered. CPX did not alter renin release when luminal NaCl was low, but diminished the reduction caused by high NaCl (P less than 0.01). It is concluded that A1-receptors are located within the JGA, and that A1-receptor activation inhibits renin release. A high NaCl concentration at the macula densa appears to influence A1-receptor activation, but a low NaCl concentration does not. The findings support participation of adenosine in macula densa control of renin secretion.
Ozone-induced Epithelial Injury in the Ferret Is Similar to Nonhuman Primates
Authors: ANJA STERNER-KOCK, MARTIN KOCK, RUEDI BRAUN, DALLAS M. HYDE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Extrapolation to humans from rodent ozone exposure is limited by the anatomic differences between the species. Ferrets have similar pulmonary structures to humans, with well developed respiratory bronchioles and submucosal glands. We exposed adult ferrets, monkeys, and rats to 1 ppm ozone (O(3)) or filtered air for 8 h followed by 1 h in filtered air. Bronchoalveolar lavage (BAL) analysis, histopathology, and confocal microscopy were used to evaluate ozone-induced epithelial injury and inflammation. BAL showed significantly increased numbers of neutrophils in ozone-exposed as compared with filtered air ferrets, monkeys, and rats. However, there were 3- to 4-fold more neutrophils in monkeys and ferrets per milliliter of BAL than in rats. Ozone-exposed lungs showed a severe, acute infiltration of neutrophils in regions with necrotic epithelial cells, especially in the centriacinar region that was more severe in ferrets and monkeys than rats. We conclude that acute ozone exposure in ferrets induce severe epithelial necrosis and inflammation, results in similar epithelial injury compared with monkeys, and represents a better model of humans than rodents.
TWO CASES OF BRAIN TUMOR WHERE OPTIC NEURITIS WAS THE ONLY POSITIVE SIGN—AUTOPSIES.Read before the Section on Ophthalmology at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: EDWARD P. MORROW
Journal: JAMA (1893)

Although pathognomonic symptom is a term in medicine, yet taken in its strict interpretation we have no symptom by which we can positively determine a disease without question. Taken in its better sense, a characteristic symptom of a disease, we may call optic neuritis a pathognomonic symptom of brain tumor. This has been so well established that it needs no discussion. The object of this report is not to further establish that fact, but to present two cases where optic neuritis was the first, and up to the time of its discovery, the only positive sign upon which a diagnosis could be based. For that reason I take it, brain tumor, with its ophthalmic aspects may be worthy of a discussion here, inasmuch as the ophthalmologist is sometimes called upon to give his opinion and to aid in the diagnosis of a case. To give positive or negative evidence as
Biliary Pleural Fistula Detected by Hepatobiliary Scintigraphy
Authors: May L. Yong, Judith M. Joyce, Lee M. Weinberg, Neil A. Christie
Journal: Clinical Nuclear Medicine (2005)

A biliary pleural fistula is a rare complication secondary to trauma, infection, malignancy, biliary disease, malignancies, or percutaneous procedures. Its presence may be suggested by the development of a right pleural effusion in a patient with such history and can be confirmed with a hepatobiliary scan or endoscopic retrograde cholangiopancreatography. Patients are treated with antibiotics and the fistula usually spontaneously closes. If after 2 weeks the fistula persists, percutaneous drainage, sphincterotomy, or biliary stent placement can be performed to promote healing of the fistula. In complicated cases, open thoracic surgery or video-assisted thoracic surgery may be required.
A STUDY OF THE BLOOD IN BANTI'S DISEASE BEFORE AND AFTER SPLENECTOMY.
Authors: WALTER L. BIERRING
Journal: JAMA (1906)

The patient on whose case this study is based was admitted to the University Hospital, Nov. 15, 1904, and presented the following history: <h3>Patient.</h3> —Mr. C. F. H., aged 38, traveling man, married, having 3 children in good health, was referred by Dr. W. E. Patterson and entered the hospital complaining of feeling of heaviness in abdomen with bloating after meals. <h3>History.</h3> —Father died at age of 72 years from hernia; mother aged 72, alive and well; three sisters alive and well; one brother died, aged 44, of typhoid fever. Patient used alcohol moderately until beginning of present illness; tea and coffee moderately. He has had gonorrhea a number of times; denies lues; had common diseases of childhood. He had spinal meningitis at 7 years of age. While in the South, at the age of 21, he had malarial fever, paroxysms ocurring, as he claims, only once a week. These
Self-Reported Conflicts of Interest of Authors, Trial Sponsorship, and the Interpretation of Editorials and Related Phase III Trials in Oncology
Authors: Giovanni M. Bariani, Anezka C.R. de Celis Ferrari, Paulo M. Hoff, Monika K. Krzyzanowska, Rachel P. Riechelmann
Journal: Journal of Clinical Oncology (2013)

Growing participation by industry in cancer research has resulted in increased reporting of conflicts of interest (COI). We aimed to test any association between authors' conclusions and self-reported COI or trial sponsorship in cancer studies.Editorials and related phase III trials published in six clinical oncology journals in the last 3.5 years were analyzed independently by two investigators who classified study conclusions according to authors' endorsement of the experimental therapy. Logistic regression multivariable models were used to assess predictors of favorable conclusions of editorialists and of phase III authors.From January 2008 to October 2011, 1,485 articles were retrieved: 150 phase III trials and 150 editorials were eligible. Among the phase III trials, 82 (54.7%) had positive results, and 78 (52.0%) were entirely or partially funded by industry. Any COI were disclosed in 103 phase III trials (68.7%) and in 71 editorials (47.3%). Multivariable analysis showed that phase III trial results were the only significant predictor for a positive conclusion by trial authors (odds ratio [OR], 92.2; 95% CI, 19.7 to 431.6; P < .001). Sponsorship did not predict for positive conclusion by phase III authors (OR, 0.86; 95% CI, 0.3 to 2.5; P = .788). The only factor associated with positive conclusions by editorial authors was a positive conclusion by phase III trial authors (OR, 36.3; 95% CI, 6.8 to 194.2; P < .001).The interpretation of recently published phase III cancer trials by their authors or by editorialists was not influenced by financial relationships or industry sponsorship. Increased awareness of COI policies may have led to more integrity in cancer research reporting.
Defective Chemotaxis Associated with a Serum Inhibitor in Cirrhotic Patients
Authors: Anthony N. DeMeo, Burton R. Andersen, Denis K. English, Jan Peterson
Journal: New England Journal of Medicine (1972)

In 22 alcoholics with active liver disease, we studied neutrophilic chemotaxis, serum hemolytic complement (C) and the complement components C 1q, C 1s, C 3, C 4, C 5 and C 3 proactivator. The cirrhotic patients had marked impairment of chemotaxis, with a mean count of 35 cells per high-power field, whereas controls had 133 cells per high-power field. Normal white cells tested with patients' serum had defective chemotaxis; however, three of four patients' cells tested with normal serum had a normal chemotactic response. In 12 patients tested, C and C 3 levels were decreased. Five of six patients' serums added to normal chemotactically active serum inhibited the expected chemotactic response. Casein-induced chemotaxis, which is C independent, was also abolished by the serum of cirrhotic patients. This defective chemotaxis may help explain the increased susceptibility to infection in cirrhosis.