tbuckley/cabot-search huggingface dataset:
Morphometric analysis of the composition of atherosclerotic plaques in the four major epicardial coronary arteries in acute myocardial infarction and in sudden coronary death.
Authors: A H Kragel, S G Reddy, J T Wittes, W C Roberts
Journal: Circulation (1989)

We studied at necropsy atherosclerotic plaque composition in the four major (right, left main, left anterior descending, and left circumflex) epicardial coronary arteries in 15 patients who died of consequences of an acute myocardial infarction (AMI) and in 12 patients with sudden coronary death (SCD) without AMI. The coronary epicardial arteries were sectioned at 5-mm intervals, and a Movat-stained section of each segment of artery was prepared and analyzed using a computerized morphometry system. Within the AMI group and within the SCD group, there were no differences in plaque composition among any of the four major epicardial coronary arteries. Within both groups, plaque morphology varied as a function of cross-sectional-area narrowing of the segments. In both groups, the amount of dense relatively acellular fibrous tissue, calcified tissue, and pultaceous debris (amorphous debris containing cholesterol clefts, presumably rich in extracellular lipid) increased in a linear fashion with increasing degrees of cross-sectional-area narrowing of the segments, and the amount of cellular fibrous tissue decreased linearly. In the AMI group, the percentage of plaque consisting of pultaceous debris and of cellular fibrous tissue separated significantly narrowed (greater than 75% cross-sectional area) segments from less narrowed (less than 75%) segments. A comparison of the AMI group to the SCD group showed significant differences. The percentage of plaque consisting of pultaceous debris (16% in the AMI group and 7% in the SCD group), of cellular fibrous tissue (11% vs. 18%), and of heavily calcified tissue (8% vs. 16%) were significantly different in the severely narrowed segments in the AMI and SCD groups. When all arteries containing thrombi were deleted from the analysis, there were no significant changes in the results. Occlusive coronary thrombi were present in 13 of the 15 AMI patients and in one of the 12 SCD patients. Thus, the frequency of coronary thrombi and plaque composition differ in patients with AMI and in those with SCD without AMI.
Antiinflammatory Effects of Salmeterol after Inhalation of Lipopolysaccharide by Healthy Volunteers
Authors: Nico A. Maris, Alex F. de Vos, Mark C. Dessing, C. Arnold Spek, Rene Lutter, Henk M. Jansen, Jaring S. van der Zee, Paul Bresser, Tom van der Poll
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Salmeterol is a beta2-adrenoreceptor agonist used in the treatment of obstructive pulmonary disease. Salmeterol inhibits inflammatory responses by neutrophils and mononuclear cells in vitro and in mouse models of lung inflammation in vivo.To determine the effect of salmeterol on LPS-induced lung inflammation in humans.Thirty-two healthy subjects were enrolled in a single-blinded, placebo-controlled study. Subjects inhaled 100 microg salmeterol or placebo (t=-0.5 h) followed by 100 microg LPS or normal saline (t=0 h; n=8/group). Measurements were performed in bronchoalveolar lavage fluid and purified alveolar macrophages obtained 6 h post-challenge.Inhalation of LPS was associated with neutrophil influx, neutrophil degranulation (myeloperoxidase, bactericidal/permeability-increasing protein and elastase), release of cytokines (tumor necrosis factor alpha and interleukin 6) and chemokines (interleukin 8, epithelial cell-derived neutrophil attractant 78, macrophage inflammatory proteins 1alpha and 1beta), activation of alveolar macrophages (upregulation of HLA-DR and CD71; enhanced expression of mRNAs for 13 different mediators of inflammation), and protein leakage (all p<0.05 vs. placebo/saline). Pretreatment with salmeterol inhibited LPS-induced neutrophil influx, neutrophil degranulation (myeloperoxidase), tumor necrosis factor alpha release, and HLA-DR expression (all p<0.05 vs. placebo/LPS), while not significantly influencing other responses.Salmeterol exerts antiinflammatory effects in the pulmonary compartment of humans exposed to LPS.
Low Dopamine D<sub>2</sub>Receptor Binding in Subregions of the Thalamus in Schizophrenia
Authors: Fumihiko Yasuno, Tetsuya Suhara, Yoshiro Okubo, Yasuhiko Sudo, Makoto Inoue, Tetsuya Ichimiya, Akihiro Takano, Kazuhiko Nakayama, Christer Halldin, Lars Farde
Journal: American Journal of Psychiatry (2004)

Several structural and functional brain imaging studies have pointed to a disturbance of thalamic subnuclei in patients with schizophrenia. The dopamine hypothesis of schizophrenia has, however, not been thoroughly examined in terms of this complex structure, which has connections with most brain regions of central interest in schizophrenia research. The aim of the present study was to examine dopamine D(2) receptor binding in subregions of the thalamus in patients with schizophrenia.The authors used positron emission tomography and the radioligand [(11)C]FLB457 to examine dopamine D(2) receptor binding in thalamic subregions of 10 drug-naive patients with schizophrenia. Binding potential was calculated by the reference tissue method and used as an index for dopamine D(2) receptor binding. Comparisons were made with 19 healthy subjects. Subregions of interest were defined on individual magnetic resonance images using a percentage-based operational approach. Clinical symptoms were rated by using the Brief Psychiatric Rating Scale (BPRS).The [(11)C]FLB457 binding potential was lower in the central medial and posterior subregions of the thalamus in patients with schizophrenia. At a functional level, there was a significant negative correlation between binding potential and BPRS positive symptom scores.The subregions with low D(2) receptor binding comprise primarily the dorsomedial nucleus and pulvinar, two important components in circuitries previously suggested in the pathophysiology of schizophrenia. Aberrant dopaminergic neurotransmission in thalamic subregions might be a mechanism underlying positive symptoms in schizophrenia.
Adaptive Evolution of Hepcidin Genes in Antarctic Notothenioid Fishes
Authors: Qianghua Xu, Chi-Hing Christina Cheng, Peng Hu, Hua Ye, Zuozhou Chen, Lixue Cao, Lei Chen, Yu Shen, Liangbiao Chen
Journal: Molecular Biology and Evolution (2008)

Hepcidin is a small bioactive peptide with dual roles as an antimicrobial peptide and as the principal hormonal regulator of iron homeostasis in human and mouse. Hepcidin homologs of very similar structures are found in lower vertebrates, all comprise approximately 20-25 amino acids with 8 highly conserved cysteines forming 4 intramolecular disulfide bonds, giving hepcidin a hairpin structure. Hepcidins are particularly diverse in teleost fishes, which may be related to the diversity of aquatic environments with varying degree of pathogen challenge, oxygenation, and iron concentration, factors known to alter hepcidin expression in mammals. We characterized the diversity of hepcidin genes of the Antarctic notothenioid fishes that are endemic to the world's coldest and most oxygen-rich marine water. Notothenioid fishes have at least 4 hepcidin variants, in 2 distinctive structural types. Type I hepcidins comprise 3 distinct variants that are homologs of the widespread 8-cysteine hepcidins. Type II is a novel 4-cysteine variant and therefore only 2 possible disulfide bonds, highly expressed in hematopoietic tissues. Analyses of d(N)/d(S) substitution rate ratios and likelihood ratio test under site-specific models detected significant signal of positive Darwinian selection on the mature hepcidin-coding sequence, suggesting adaptive evolution of notothenioid hepcidins. Genomic polymerase chain reaction and Southern hybridization showed that the novel type II hepcidin occurs exclusively in lineages of the Antarctic notothenioid radiation but not in the basal non-Antarctic taxa, and lineage-specific positive selection was detected on the branch leading to the type II hepcidin clade under branch-site models, suggesting adaptive evolution of the reduced cysteine variant in response to the polar environment. We also isolated a structurally distinct 4-cysteine (4cys) hepcidin from an Antarctic eelpout that is unrelated to the notothenioids but inhabits the same freezing water. Neighbor-Joining (NJ) analyses of teleost hepcidins showed that the eelpout 4cys variant arose independently from the notothenioid version, which lends support to adaptive evolution of reduced cysteine hepcidin variants on cold selection. The NJ tree also showed taxonomic-specific expansions of hepcidin variants, indicating that duplication and diversification of hepcidin genes play important roles in evolutionary response to diverse ecological conditions.
Plasmalemmal Vesicle Associated Protein-1 Is a Novel Marker Implicated in Brain Tumor Angiogenesis
Authors: Eleanor B. Carson-Walter, Jessica Hampton, Eveline Shue, Daniel M. Geynisman, Pramod Kumar Pillai, Ramasri Sathanoori, Stephen L. Madden, Ronald L. Hamilton, Kevin A. Walter
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Plasmalemmal vesicle associated protein-1 (PV-1) is up-regulated in the endothelium of human glioblastoma. We sought to further characterize the expression pattern of PV-1 in human brain tumors and interrogate its role in brain tumor angiogenesis. Experimental Design: Quantitative reverse transcription-PCR and in situ hybridization were used to measure PV-1 expression in a panel of 46 human brain tumors and related pathologic states. Matrigel tubulogenesis assays and cell migration assays were used to show function of PV-1 in primary human endothelial cells (HMVEC) under gene knockdown conditions. Results: PV-1 is selectively up-regulated in a variety of high-grade human brain tumors, including glioblastoma and metastatic carcinoma, as well as other cerebral disorders associated with blood-brain barrier disruption, such as acute ischemia. Expression levels were reduced in low-grade neoplasia; however, tumors associated with the ependyma and choroid plexus, known sites of PV-1 expression, also exhibited robust expression. Cerebral expression of PV-1 mRNA was confined to endothelial cells in all cases. PV-1 expression was induced in HMVEC cells in vitro by exposure to medium conditioned by U87MG and U251MG human brain tumor cell lines and by medium supplemented with exogenous vascular endothelial growth factor or scatter factor/hepatocyte growth factor. RNA interference–mediated inhibition of PV-1 induction in HMVEC cells blocked Matrigel-induced tubulogenesis and inhibited cell migration induced by conditioned medium or angiogenic growth factors. Conclusions: Our results confirm that PV-1 is preferentially induced in the endothelium of high-grade human brain tumors. Inhibition of PV-1 expression is associated with failure of endothelial differentiation in vitro. PV-1 represents a novel marker of brain tumor angiogenesis and integrity of the blood-brain barrier and is a potential therapeutic target.
Leprosy type 1 reaction spares the scars in a patch of borderline tuberculoid leprosy
Authors: S.L. Walker, T.G. Lewis, K. Mahat, R.A. Hawksworth
Journal: British Journal of Dermatology (2008)

Journal Article Leprosy type 1 reaction spares the scars in a patch of borderline tuberculoid leprosy Get access S.L. Walker, S.L. Walker London School of Hygiene and Tropical Medicine, London WC1E 7HT, U.K.Anandaban Hospital, PO Box 151, Kathmandu, Nepal E‐mail: drstevewalker@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar T.G. Lewis, T.G. Lewis Anandaban Hospital, PO Box 151, Kathmandu, Nepal E‐mail: drstevewalker@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar K. Mahat, K. Mahat Anandaban Hospital, PO Box 151, Kathmandu, Nepal E‐mail: drstevewalker@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar R.A. Hawksworth R.A. Hawksworth Anandaban Hospital, PO Box 151, Kathmandu, Nepal E‐mail: drstevewalker@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 3, 1 March 2008, Pages 648–649, https://doi.org/10.1111/j.1365-2133.2007.08395.x Published: 01 March 2008
Correlated expression of T cell growth factor dependence, sensitivity to Vicia villosa lectin, and cytolytic activity in hybrids between cytolytic T cells and T lymphomas.
Authors: A Conzelmann, A Silva, M Cianfriglia, C Tougne, R P Sekaly, M Nabholz
Journal: The Journal of Experimental Medicine (1982)

Somatic cell fusion between cytolytically active, T cell growth factor- (TCGF) dependent murine T cell lines (CTL lines) and noncytolytic, TCGF-independent murine T lymphoma lines has yielded two types of somatic cell hybrids (5): cytolytic hybrids, growth of which is dependent on TCGF, and hybrids with very weak or undetectable cytolytic activity which grow at the same rate with or without TCGF. Here we report that the former can produce stable variants that resemble the latter type. Some of these TCGF-independent variants still have TCGF receptors. High susceptibility to the cytotoxic effects of Vicia villosa lectin, a marker distinguishing the parental CTL lines from T lymphomas, is expressed by the TCGF-dependent hybrids but not by the TCGF-independent variants. The two types of hybrids also differ in the expression of surface glycoproteins. We propose that there exists a genetic element in the CTL line that represses the TCGF-independent replication mechanism of the T lymphoma parent in the TCGF-dependent hybrids and that this genetic element is lost or switched off in the TCGF-independent variants.
Intestinal Non-Hodgkin’s Lymphoma: A Multicenter Prospective Clinical Study From the German Study Group on Intestinal Non-Hodgkin’s Lymphoma
Authors: Severin Daum, Reiner Ullrich, Walter Heise, Bettina Dederke, Hans-Dieter Foss, Harald Stein, Eckhard Thiel, Martin Zeitz, Ernst-Otto Riecken
Journal: Journal of Clinical Oncology (2003)

Intestinal non-Hodgkin's lymphomas are not well characterized. We therefore studied prospectively their clinical features and response to standardized therapy.Fifty-six patients with primary intestinal lymphoma were included in a prospective, nonrandomized multicenter study. Lymphoma resection was recommended and staging was performed according to the Ann Arbor classification. Patients were scheduled to receive six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy, and at stages EIII to EIV, they received additional involved-field radiotherapy. Corticosteroids were used in patients who could not receive chemotherapy.Thirty-five patients had intestinal T-cell lymphoma (ITCL), 21 patients had intestinal B-cell lymphoma (IBCL; 18 diffuse large-cell lymphomas, two marginal-cell lymphomas, and one follicle-center lymphoma). Thirty-four patients at stages EI to EII (14 ITCL and 20 IBCL) and nine patients at stages EIII to EIV (all ITCL) received chemotherapy. No patient in stages EIII to EIV received radiotherapy, because death occurred in 12 of 14 patients. Two-year cumulative survival in patients with IBCL was 94% (95% CI, 82% to 100%) and higher than in patients with ITCL (28% [95% CI, 13% to 43%]; P <.0001), even when only stages EI to EII were considered (ITCL, 37.5% [95% CI, 16.5% to 58.5%]; P <.0001). IBCL patients compared with ITCL patients were at lower lymphoma stages (P <.01), had higher Karnofsky status (P <.005), had intestinal perforation less often (P <.05), required emergency operation less often (P <.05), received CHOP (P <.05) more often, and reached complete remission (P <.0005) more frequently.IBCL patients at stages EI and EII respond well to chemotherapy, but the prognosis and treatment of ITCL patients is unsatisfactory.
Digitalis Therapy for Patients in Clinical Heart Failure
Authors: Shahbudin H. Rahimtoola
Journal: Circulation (2004)

T he most commonly used preparation of digitalis is digoxin, which is obtained from the leaves of Digitalis lanata, a common flowering plant called "foxglove."The words digitalis and digoxin in this article are used interchangeably.An exhaustive review published in 1996 1 cited a large number of references and had detailed data and descriptions of a large number of studies and all early trials.The present article summarizes those data but focuses on and emphasizes data collected since that time. Actions of Cardiac GlycosidesThese have been described in detail previously 1 and are briefly summarized. Inotropic EffectsThe inotropic effects have been documented in the isolated papillary muscles and in the normal hearts of animals and humans.The inotropic action occurs in both ventricles and in both atria.In the normal heart and in those with coronary artery disease and normal left ventricular (LV) systolic function, with digitalis the LV function curve is moved upward and to the left. 1 As a result, LV end-diastolic pressure and LV end-diastolic and end-systolic volumes are reduced, and there is an increase of LV ejection fraction (LVEF).
Diagnostic Accuracy of Colorectal Cancer Staging With Whole-Body PET/CT Colonography
Authors: Patrick Veit-Haibach, Christiane A. Kuehle, Thomas Beyer, Hrvoje Stergar, Hilmar Kuehl, Johannes Schmidt, Gereon Börsch, Gerlinde Dahmen, Joerg Barkhausen, Andreas Bockisch, Gerald Antoch
Journal: JAMA (2006)

Staging of patients with colorectal cancer often requires a multimodality, multistep imaging approach. Colonography composed of a combined modality of positron emission tomography (PET) and computed tomography (CT) provides whole-body tumor staging in a single session.To determine the staging accuracy of whole-body PET/CT colonography compared with the staging accuracies of CT followed by PET (CT + PET) and CT alone and to evaluate the effect of PET/CT colonography on therapy planning compared with conventional staging (CT of the abdomen and thorax and optical colonoscopy).Prospective study of 47 patients enrolled between May 2004 and June 2006 with clinical findings and optical colonoscopy that suggested primary colorectal cancer (mean [SD] age, 71 [11] years; range, 47-92 years). Patients underwent whole-body PET/CT colonography 1 day after colonoscopy. The study was conducted at a university hospital with a mean (SD) follow-up of 447 (140) days (range, 232-653 days).Correct classification of overall TNM stage using PET/CT colonography compared with CT + PET and CT alone. Secondary outcome measures were the accurate assessment of T-stage, N-stage, and M-stage by PET/CT colonography compared with CT + PET and CT alone and the effect of PET/CT colonography on therapy planning.Of the 47 patients with a total of 50 lesions, the overall TNM stage was correctly determined for 37 lesions with PET/CT colonography (74%; 95% confidence interval [CI], 60%-85%), 32 lesions with CT + PET (64%; 95% CI, 49%-77%), and 26 lesions with CT alone with a 0.7-cm node threshold (52%; 95% CI, 37%-66%). Compared with optimized abdominal CT staging alone, PET/CT colonography was significantly more accurate in defining TNM stage (difference, 22%; 95% CI, 9%-36%; P=.003), which was mainly based on a more accurate definition of the T-stage. Differences were not detected for defining N-stage between PET/CT colonography and CT alone with a threshold of 0.7 cm for malignant nodes but were detected with a threshold of 1 cm. Differences were not detected in defining M-stage separately or when comparing the accuracies of PET/CT colonography with CT + PET. PET/CT colonography affected consecutive therapy decisions in 4 patients (9%; 95% CI, 2.4%-20.4%) compared with conventional staging (CT alone and colonoscopy).In this preliminary study, PET/CT colonography is at least equivalent to CT + PET for tumor staging in patients with colorectal cancer. Thus, PET/CT colonography in conjunction with optical colonoscopy may be a suitable concept of tumor staging for patients with colorectal cancer.
Minoxidil: mechanisms of action on hair growth
Authors: A.G. Messenger, J. Rundegren
Journal: British Journal of Dermatology (2004)

We have known for over 30 years that minoxidil stimulates hair growth, yet our understanding of its mechanism of action on the hair follicle is very limited. In animal studies, topical minoxidil shortens telogen, causing premature entry of resting hair follicles into anagen, and it probably has a similar action in humans. Minoxidil may also cause prolongation of anagen and increases hair follicle size. Orally administered minoxidil lowers blood pressure by relaxing vascular smooth muscle through the action of its sulphated metabolite, minoxidil sulphate, as an opener of sarcolemmal KATP channels. There is some evidence that the stimulatory effect of minoxidil on hair growth is also due to the opening of potassium channels by minoxidil sulphate, but this idea has been difficult to prove and to date there has been no clear demonstration that KATP channels are expressed in the hair follicle. A number of in vitro effects of minoxidil have been described in monocultures of various skin and hair follicle cell types including stimulation of cell proliferation, inhibition of collagen synthesis, and stimulation of vascular endothelial growth factor and prostaglandin synthesis. Some or all of these effects may be relevant to hair growth, but the application of results obtained in cell culture studies to the complex biology of the hair follicle is uncertain. In this article we review the current state of knowledge on the mode of action of minoxidil on hair growth and indicate lines of future research.
REDUCTION OF EXCESS CHOLESTEROL IN THE RABBIT AORTA BY INHIBITION OF ENDOGENOUS CHOLESTEROL SYNTHESIS
Authors: George L. Curran, Richard L. Costello
Journal: The Journal of Experimental Medicine (1956)

Hepatic cholesterol synthesis in rabbits, as measured by the incorporation of C(14)-labelled acetate, was inhibited by addition of non-toxic amounts of vanadyl sulfate (0.05 per cent VOSO(4).2H(2)O) to the diet. This diet reduced excess aortic cholesterol in cholesterol prefed rabbits when fed during the 6 weeks immediately following a 4 week period of cholesterol feeding.