tbuckley/cabot-search huggingface dataset:
Endothelin-A Receptor Antagonist–Mediated Vasodilatation Is Attenuated by Inhibition of Nitric Oxide Synthesis and by Endothelin-B Receptor Blockade
Authors: Marianne C. Verhaar, Fiona E. Strachan, David E. Newby, Nicholas L. Cruden, Hein A. Koomans, Ton J. Rabelink, David J. Webb
Journal: Circulation (1998)

The role of endothelin (ET)-1 in maintenance of basal vascular tone has been demonstrated by local and systemic vasodilatation to endothelin receptor antagonists in humans. Although the constrictor effects mediated by the vascular smooth muscle ET(A) receptors are clear, the contribution from endothelial and vascular smooth muscle ET(B) receptors remains to be defined. The present study, in human forearm resistance vessels in vivo, was designed to further investigate the physiological function of ET(A) and ET(B) receptor subtypes in human blood vessels and determine the mechanism underlying the vasodilatation to the ET(A)-selective receptor antagonist BQ-123.Two studies were performed, each in groups of eight healthy subjects. Brachial artery infusion of BQ-123 caused significant forearm vasodilatation in both studies. This vasodilatation was reduced by 95% (P=.006) with inhibition of the endogenous generation of nitric oxide and by 38% (P<.001) with coinfusion of the ET(B) receptor antagonist BQ-788. In contrast, inhibition of prostanoid generation did not affect the response to BQ-123. Infusion of BQ-788 alone produced a 20% reduction in forearm blood flow (P<.001).Selective ET(A) receptor antagonism causes vasodilatation of human forearm resistance vessels in vivo. This response appears to result in major part from an increase in nitric oxide generation. ET(B) receptor antagonism either alone or on a background of ET(A) antagonism causes local vasoconstriction, indicating that ET(B) receptors in blood vessels respond to ET-1 predominantly by causing vasodilatation.
Dosimetric implications of pulmonary macrophage clusters observed within lungs of rats that have inhaled enriched UO2 particles.
Authors: K J Morris, C L Barker, A L Batchelor, P Khanna
Journal: Environmental Health Perspectives (1992)

Twenty-four Fischer 344 rats were exposed to enriched uranium dioxide (UO2) aerosols to give a mean initial lung burden of 291 +/- 89 (SD) micrograms. Groups of rats were killed at 1, 7, 180, 360, 540, and 720 days post-inhalation (PI). Their lungs were fixed and inflated. Sections cut from all five lung lobes were used to prepare CR-39 neutron-induced 235U fission fragment autoradiographs. A single traverse across a CR-39 autoradiograph of a tissue section, from the left lung of all the rats, was made using a motorized microscopic stage. The traverse was divided into 10 fields. The track counts per field were used to test for homogeneity of track distribution and to assess if there was any tendency for tracks to be related to the peripheral region of the lung. Full raster scans across the entire tissue image were made on left lung autoradiographs from two animals killed at each time point to assess the homogeneity of fission fragment track distribution throughout the entire section. There was no evidence of any temporal change in the proportion of tracks associated with the lung periphery. At all time points PI, the track distribution was significantly nonhomogeneous, suggesting a nonuniform pattern of tissue irradiation from the 234U alpha particles. At time points from 180 to 720 days PI, large clusters of macrophages were observed in some of the sections taken from all five lung lobes. The total number of macrophage clusters increased with time PI. These macrophage clusters produced many 235U fission fragment tracks within the CR-39 autoradiographs.(ABSTRACT TRUNCATED AT 250 WORDS)
Predictors of local adverse effects caused by topical tretinoin cream 0·1% in the Veterans Affairs Topical Tretinoin Chemoprevention trial
Authors: H. Pomerantz, M.A. Weinstock
Journal: British Journal of Dermatology (2014)

Topical tretinoin is commonly prescribed, but its frequent adverse effects are barriers to use. Predictors of resistance or susceptibility to retinoid irritation are not known. To identify baseline patient characteristics associated with adverse effects of topical tretinoin. This cohort study used data collected from 324 participants in the Veterans Affairs Topical Tretinoin Chemoprevention trial who were randomized to apply tretinoin cream on the face and ears. Univariate and multivariate logistic regression models were used to examine the associations between baseline characteristics and local adverse effects. One hundred and ninety-seven patients (61% of those randomized to tretinoin) reported local adverse effects within 6 months. Clinical signs of severe photodamage at baseline [odds ratio (OR) 0·15, 95% confidence interval (CI) 0·04-0·54] and history of acne (OR 0·46, 95% CI 0·27-0·77) were associated with a decreased risk of adverse effects to tretinoin. The use of other topical medications at enrolment (OR 1·88, 95% CI 1·15-3·08) predicted an increase in adverse effects. In this study population, the common indications of topical tretinoin treatment were associated with lower risks of adverse effects. The concurrent use of other topical medications may worsen irritation caused by tretinoin.
A no biopsy strategy for adult patients with suspected coeliac disease: making the world gluten-free
Authors: Matthew Kurien, Jonas F Ludvigsson, David S Sanders
Journal: Gut (2014)

Austin and colleagues1 offer an opinion that the recent BSG guidelines on adult coeliac disease are regressive for not considering a biopsy avoidance strategy in patients with positive serological findings.2 The authors cite a positive predictive value (PPV) of up to 100% for serological testing, however studies reporting these findings are from highly selected populations where coeliac disease prevalence is high (six studies, coeliac disease prevalence between 21% and 100%). The most important data that clearly refutes Austin and colleagues’ suggestion is a study of 2000 patients attending endoscopy, where coeliac disease prevalence was 3.9%.3 In this study the PPV of anti-tissue transglutaminase antibody (tTG) was only 28.6%, despite sensitivity and specificity of greater than 90%, which only increased to 71.7% when combined with a positive endomysial antibody (EMA). In simple terms if we follow the approach advocated by Austin and colleagues 3 out of 10 patients would be placed on a …
Anti‐Allergic Activity of Formoterol, a New Beta‐Adrenoceptor Stimulant, and Salbutamol in Human Leukocytes and Human Lung Tissue
Authors: HARUHISA MITA, TAKAO SHIDA
Journal: Allergy (1983)

Formoterol and salbutamol were compared for in vitro inhibition of allergen‐induced histamine release from allergic leukocytes and human lung tissue passively sensitized with allergic serum. Formoterol inhibited the release of histamine from leukocytes but salbutamol showed little inhibiting effect. When combined with theophylline, formoterol was a more potent inhibitor of the release of histamine from leukocytes in allergic patients than salbutamol. In fragments of human lung sensitized with allergic serum, the concentration required to inhibit histamine release by 50% was 2 × 10 −11 M for formoterol and 8.5 × 10 −9 M for salbutamol. The potency of salbutamol and formoterol in blocking specific 3 H‐dihydroalprenolol binding to beta‐adrenoceptors on guinea pig lung membranes revealed that formoterol had higher affinity for beta‐adrenoceptors than salbutamol, and the concentration required for half‐maximum stimulation of adenylate cyclase was approximately 200‐fold higher for salbutamol than for formoterol.
DO WE STILL NEED A GLYCOPROTEIN IIB/IIIA INHIBITOR FOR ACUTE ST-SEGMENT-ELEVATION MYOCARDIAL INFARCTION IN PATIENTS UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION AND PRETREATED WITH A LOADING DOSE OF CLOPIDOGREL?
Authors: Lili Dong, Yongshi Wang, Xianhong Shu
Journal: Journal of the American College of Cardiology (2011)
Growth hormone stimulates proliferation of old-aged regenerating liver through forkhead box m1b
Authors: Katherine Krupczak-Hollis, Xinhe Wang, Margaret B. Dennewitz, Robert H. Costa
Journal: Hepatology (2003)

The Forkhead Box (Fox) proteins are an extensive family of transcription factors that shares homology in the winged helix DNA-binding domain and the members of which play essential roles in cellular proliferation, differentiation, and longevity. Reduced cellular proliferation during aging is associated with a progressive decline in both growth hormone (GH) secretion and Foxm1b expression. Liver regeneration studies with 12-month-old (old-aged) transgenic mice indicated that increased hepatocyte expression of Foxm1b alone is sufficient to restore hepatocyte proliferation to levels found in 2-month-old (young) regenerating liver. GH therapy in older people has been shown to cause an increase in cellular proliferation, but the transcription factors that mediated this stimulation in proliferation remain uncharacterized. In this study, we showed that human GH administration to old-aged Balb/c mice dramatically increased both expression of Foxm1b and regenerating hepatocyte proliferation. This increase in old-aged regenerating hepatocyte proliferation was associated with elevated protein expression of Cdc25A, Cdc25B, and cyclin B1, with reduced protein levels of cyclin-dependent kinase inhibitor p27(Kip1) (p27). GH treatment also was found to stimulate hepatocyte proliferation and expression of Foxm1b protein without partial hepatectomy (PHx). Furthermore, GH treatment of young Foxm1b -/- mice failed to restore regenerating hepatocyte DNA replication and mitosis caused by Foxm1b deficiency. These genetic studies provided strong evidence that the presence of Foxm1b is essential for GH to stimulate regenerating hepatocyte proliferation. In conclusion, our old-aged liver regeneration studies show that increased Foxm1b levels are essential for GH to stimulate hepatocyte proliferation, thus providing a mechanism for GH action in the elderly.
Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency
Authors: Ricardo C Ferreira, Qiang Pan-Hammarström, Robert R Graham, Vesela Gateva, Gumersindo Fontán, Annette T Lee, Ward Ortmann, Elena Urcelay, Miguel Fernández-Arquero, Concepción Núñez, Gudmundur Jorgensen, Björn R Ludviksson, Sinikka Koskinen, Katri Haimila, Hilary F Clark, Lars Klareskog, Peter K Gregersen, Timothy W Behrens, Lennart Hammarström
Journal: Nature Genetics (2010)
Assessment of Small-Diameter Aortic Mechanical Prostheses
Authors: Richard H. Marcus, Russell S. Heinrich, James Bednarz, Stephen Lupovitch, Joseph Abruzzo, Raphael Borok, Byron Vandenberg, Richard E. Kerber, William Piccione, Ajit P. Yoganathan, Roberto M. Lang
Journal: Circulation (1998)

Background —Noninvasive assessment of functionally stenotic small-diameter aortic mechanical prostheses is complicated by theoretical constraints relating to the hemodynamic relevance of Doppler-derived transprosthetic gradients. To establish the utility of Doppler echocardiography for evaluation of these valves, 20-mm Medtronic Hall and 19-mm St Jude prostheses were studied in vitro and in vivo. Methods and Results —Relations between the orifice transprosthetic gradient (equivalent to Doppler), the downstream gradient in the zone of recovered pressure (equivalent to catheter), and fluid mechanical energy losses were examined in vitro. Pressure-flow relations across the 2 prostheses were evaluated by Doppler echocardiography in vivo. For both types of prosthesis in vitro, the orifice was higher than the downstream gradient ( P &lt;0.001), and fluid mechanical energy losses were as strongly correlated with orifice as with downstream pressure gradients ( r 2 =0.99 for both). Orifice and downstream gradients were higher and fluid mechanical energy losses were larger for the St Jude than the Medtronic Hall valve (all P &lt;0.001). Whereas estimated effective orifice areas for the 2 valves in vivo were not significantly different, model-independent dynamic analysis of pressure-flow relations revealed higher gradients for the St Jude than the Medtronic Hall valve at a given flow rate ( P &lt;0.05). Conclusions —Even in the presence of significant pressure recovery, the Doppler-derived gradient across small-diameter aortic mechanical prostheses does have hemodynamic relevance insofar as it reflects myocardial energy expenditure. Small differences in function between stenotic aortic mechanical prostheses, undetectable by conventional orifice area estimations, can be identified by dynamic Doppler echocardiographic analysis of pressure-flow relations.
INFLUENCE OF AGE ON SUSCEPTIBILITY AND ON IMMUNE RESPONSE OF MICE TO EASTERN EQUINE ENCEPHALOMYELITIS VIRUS
Authors: Isabel M. Morgan
Journal: The Journal of Experimental Medicine (1941)

The experiments described in this paper were carried out with the Rockefeller Institute strain of albino mice and with the Eastern strain of the virus of equine encephalomyelitis. 1. The observation was confirmed that with increasing age of mice there occurred a decrease in susceptibility to intraperitoneal injection of active virus; also, the length of incubation period of those which succumbed increased with age. 2. The mice of various age groups which survived an intraperitoneal injection of active virus were indistinguishable in their antibody response. 3. Young mice, vaccinated with formalin-inactivated. virus when 2, 5, and 7 days old, gave an immune response to such a degree that they showed (a) measurable peritoneal immunity which increased with small increments of age, (b) no cerebral resistance, and (c) detectable amounts of neutralizing antibody in their sera which paralleled, though at a considerably lower level, their peritoneal resistance. 4. The peritoneal resistance induced as a result of vaccination was shown to be not local, but a general, systemic immunity, specific for the Eastern strain. Such a peritoneal resistance was demonstrable by the 4th day after beginning of vaccination of 10-days-old mice. 5. After intraperitoneal injection of active virus, large amounts of virus were recoverable from the blood of non-vaccinated young mice; none was found in the blood of vaccinated young mice; a minimal amount was detectable in the blood of non-vaccinated adult mice. 6. The bearing of age on the degree of immune response of which mice are capable and on their susceptibility to the virus has been discussed.
Cellular markers that distinguish the phases of hemangioma during infancy and childhood.
Authors: K Takahashi, J B Mulliken, H P Kozakewich, R A Rogers, J Folkman, R A Ezekowitz
Journal: Journal of Clinical Investigation (1994)

Hemangiomas, localized tumors of blood vessels, appear in approximately 10-12% of Caucasian infants. These lesions are characterized by a rapid proliferation of capillaries for the first year (proliferating phase), followed by slow, inevitable, regression of the tumor over the ensuing 1-5 yr (involuting phase), and continual improvement until 6-12 yr of age (involuted phase). To delineate the clinically observed growth phases of hemangiomas at a cellular level, we undertook an immunohistochemical analysis using nine independent markers. The proliferating phase was defined by high expression of proliferating cell nuclear antigen, type IV collagenase, and vascular endothelial growth factor. Elevated expression of the tissue inhibitor of metalloproteinase, TIMP 1, an inhibitor of new blood vessel formation, was observed exclusively in the involuting phase. High expression of basic fibroblast growth factor (bFGF) and urokinase was present in the proliferating and involuting phases. There was coexpression of bFGF and endothelial phenotypic markers CD31 and von Willebrand factor in the proliferating phase. These results provide an objective basis for staging hemangiomas and may be used to evaluate pharmacological agents, such as corticosteroids and interferon alfa-2a, which accelerate regression of hemangiomas. By contrast, vascular malformations do not express proliferating cell nuclear antigen, vascular endothelial growth factor, bFGF, type IV collagenase, and urokinase. These data demonstrate immunohistochemical differences between proliferating hemangiomas and vascular malformations which reflect the biological distinctions between these vascular lesions.
Liver damage underlying unexplained transaminase elevation in human immunodeficiency virus-1 mono-infected patients on antiretroviral therapy
Authors: Patrick Ingiliz, Marc-Antoine Valantin, Claudine Duvivier, Fadia Medja, Stephanie Dominguez, Frédéric Charlotte, Roland Tubiana, Thierry Poynard, Christine Katlama, Anne Lombès, Yves Benhamou
Journal: Hepatology (2008)

Liver damage associated with chronic unexplained high serum transaminases in human immunodeficiency virus (HIV)-infected patients under combined antiretroviral therapy is unknown. Liver histology was prospectively investigated in patients presenting serum transaminase elevation for more than 6 months, after exclusion of alcohol abuse, hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, autoimmune, and genetic liver diseases. In a subgroup of patients, liver mitochondrial activities were measured by spectrophotometry and mitochondrial DNA (mtDNA) by real-time polymerase chain reaction (PCR). Thirty patients were included with median values of alanine aminotransferase (ALT) levels: 80 U/L, age: 46 years, body mass index: 23 kg/m(2), HIV RNA: 200 copies/mL, CD4 count: 365/mm(3), duration of HIV infection: 13 years, and duration of treatment exposure: 118, 41, and 53 months for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors, respectively. Histological anomalies were found in 22 of 30 patients. Steatosis was present in 18 patients, severe in nine patients, and associated with inflammation in 16 patients with a diagnosis of non-alcoholic steatohepatitis (NASH). Fibrosis was found in 18 patients, severe in six patients and associated with steatosis in 13 patients. Significant liver respiratory complex I defect, contrasting with high complex IV activity and normal mitochondrial DNA content, was observed in the group of patients compared with controls. The presence of NASH was correlated with high fasting glycemia and insulin levels, not with liver mitochondrial function or mitochondrial DNA content.HIV-infected patients on combined antiretroviral therapy with chronic transaminase elevation of unknown origin have a high rate of liver lesions, mostly consistent with NASH related to insulin resistance.
Physostigmine Reversal Of Sedative Drugs
Authors: Henry Rosenberg
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Physostigmine is an effective antidote to the central effects of scopolamine and a variety of other drugs that may have anticholinergic activity, eg, tricyclic antidepressants and antihistamines.<sup>1</sup> Animal studies have suggested that physostigmine will reverse sedation from the butyrophenone haloperidol.<sup>2</sup>In man, there are indications of its usefulness in antagonizing phenothiazine- and diazepam-induced coma.<sup>3</sup> The following case history describes the use of physostigmine in the reversal of sedation from the butyrophenone droperidol and diazepam without effecting narcotic analgesia. <h3>Report of a Case.—</h3> A healthy, but extremely anxious, 37-year-old man was scheduled to undergo right inguinal hernia repair. He was premedicated with morphine sulfate, 12 mg, diazepam, 10 mg, and atropine, 0.4 mg, one hour prior to surgery. In the operating room he was alert and cooperative but quite apprehensive. Anesthesia was induced with diazepam, 20 mg, and 5 ml of a mixture of droperidol
Limiting Myocardial Damage during Acute Myocardial Infarction by Inhibiting C-Reactive Protein
Authors: Richard N. Kitsis, Ishwarlal Jialal
Journal: New England Journal of Medicine (2006)

A recent study in a rat model of coronary-artery occlusion shows that pretreatment with 1,6-bis(phosphocholine)-hexane inhibits increased myocardial damage that results from human C-reactive protein.
Decrease in serum extracellular domain of HER2 at 4 and 8 weeks is associated with prolonged progression-free survival on lapatinib monotherapy.
Authors: A Lipton, K Leitzel, S Ali, W Carney, G Platek, L O'Rourke, A Martin, J Maltzman
Journal: Cancer Research (2009)

Abstract Abstract #3140 Background: The extracellular domain of the HER2 oncoprotein (ECD HER2) is shed into the serum and can be detected by ELISA. This study investigated whether baseline serum ECD HER2 level is associated with prolonged progression-free survival (PFS) on lapatinib monotherapy. Additionally, we analyzed whether change in serum ECD HER2 at week 4 and 8 after start of lapatinib therapy is associated with prolonged PFS.&amp;#x2028; Methods: Study EGF20009 investigated lapatinib monotherapy in 138 HER2-positive patients with metastatic breast cancer who had not previously received chemotherapy or trastuzumab. Serum was collected at baseline and every 4 weeks after initiation of oral lapatinib (1,500 mg daily or 500 mg twice daily). Disease assessment was performed at week 8, 12 and every 12 weeks thereafter. Disease status was assessed by an independent radiology committee, and response was measured using RECIST. Serum ECD HER2 was measured using the ELISA from Siemens HealthCare DX/Oncogene Science. A serum ECD HER2 decrease or increase ≥ 20% from baseline was defined as a significant change.&amp;#x2028; Results: Baseline ECD HER2 was not associated with PFS; however, a ≥ 20% decrease from baseline serum ECD HER2 was associated with prolonged PFS, and a ≥ 20% increase from baseline was associated with shorter PFS. Patients who experienced a ≥ 20% decrease from baseline serum ECD HER2 at week 4 had a median PFS of 199 days (95% confidence interval [CI] = 145, 253) compared with 135 days (95% CI = 104, 171) for patients who did not (p = 0.016). Similarly, patients who experienced a ≥ 20% increase from baseline serum ECD HER2 at week 4 had a median PFS of 113 days (95% CI = 59, 135) compared with 199 days (95% CI = 142, 253) for patients who did not (p &amp;lt; 0.001). Similar associations were observed for the week-8 changes in serum ECD HER2 levels.&amp;#x2028; Conclusions: Baseline ECD HER2 was not associated with PFS, whereas a ≥ 20% decrease from baseline serum ECD HER2 at week 4 and 8 was associated with prolonged PFS on lapatinib monotherapy. Single-agent lapatinib could be considered for the subset of patients whose ECD HER2 declines in the first 8 weeks of therapy, whereas a combination of chemotherapy with anti-HER2 therapy may be more appropriate for the patients whose ECD increases by ≥ 20%. Identification of a subgroup of patients who may be able to avoid cytotoxic chemotherapy in the MBC setting is an attractive prospect in our quest to find suitable therapies for appropriate patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3140.
Medicine and the Gulag
Authors: I. Kosserev, R. Crawshaw
Journal: BMJ (1994)

The nature of the medical treatment of prisoners in the Gulag has emerged from accounts published by survivors. Over a period of 70 years some doctors entrusted with the medical care of prisoners failed to discharge their ethical duties, contributing to the prisoners' neglect and suffering. The medical profession must carefully examine what occurred and properly assign responsibility for ethical as well as unethical medical acts. Understanding the history of these ominous events will alert doctors worldwide to the importance of medical autonomy in the support of imprisoned patients.