tbuckley/cabot-search huggingface dataset:
The Systemic Inflammatory Response Syndrome in Acute Liver Failure
Authors: Nancy Rolando, Jim Wade, Milagros Davalos, Julia Wendon, John Philpott-Howard, Roger Williams
Journal: Hepatology (2000)

The systemic inflammatory response syndrome (SIRS) in acute liver failure (ALF), in which infection is common, has not been studied. In this study, SIRS components were recorded on admission and during episodes of infection, in 887 ALF patients admitted to a single center during an 11-year period. Overall, 504 (56.8%) patients manifested a SIRS during their illness, with a maximum of 1, 2, and 3 concurrent SIRS components in 166, 238, and 100 patients, respectively. In 353 (39.8%) patients who did not become infected, a SIRS on admission was associated with a more critical illness, subsequent worsening of encephalopathy, and death. Infected patients more often developed a SIRS and one of greater magnitude. The magnitude of the SIRS in 273 patients with bacterial infection correlated with mortality, being 16.7%, 28.4%, 41.2%, and 64.7% in patients with 0, 1, 2, and 3 maximum concurrent SIRS components, respectively. Similar correlations with mortality were seen for SIRS associated with fungal infection, bacteremia, and bacterial chest infection. Fifty-nine percent of patients with severe sepsis died, as did 98% of those with septic shock. A significant association was found between progressive encephalopathy and infection. Infected patients with progressive encephalopathy manifested more SIRS components than other infected patients. For patients with a SIRS, the proportions of infected and noninfected patients manifesting worsening encephalopathy were similar. In ALF, the SIRS, whether or not precipitated by infection, appears to be implicated in the progression of encephalopathy, reducing the chances of transplantation and conferring a poorer prognosis.
Gastroesophageal Reflux Disease and Progressive Nephropathy After Improving Glycemic Control in an Adolescent With Diabetic Dwarfism
Authors: Chung-Jung Wu
Journal: Diabetes Care (2002)

Since the description of Mauriac’s syndrome, or diabetic dwarfism, in 1930s, this syndrome, consisting of growth retardation, delayed puberty, and hepatomegaly, has rarely been encountered in type 1 diabetic children, especially since the advent of better diabetic management by insulin administration. The cause of growth failure has remained obscure, although it is presumably related to poor metabolic control of diabetes and depressed IGF-1 values (1). Improving diabetic control can result in the resolution of Mauriac’s syndrome. However, the clinical response may not be complete and may even result in progressive deterioration of microvascular complications, such as retinopathy or nephropathy (2,3).

We report here a 19-year-old adolescent with 10 years’ duration of type 1 diabetes and typical features of Mauriac’s syndrome who developed gastroesophageal reflux disease (GERD) and progressive nephropathy after improving glycemic control. Since the onset of his overt disease, he received suboptimal insulin therapy (4–10 units/day). He was referred 3 years ago with the problems of short stature and …
Prevalence of snoring and sleep breathing-related disorders in Chinese, Malay and Indian adults in Singapore
Authors: TP Ng, A Seow, WC Tan
Journal: European Respiratory Journal (1998)

This study investigated the prevalence of snoring and symptoms of sleep breathing-related disorders in the multi-ethnic population of Singapore (3 million people, comprising 75% Chinese, 15% Malay and 7% Indian). A multistaged, area cluster, disproportionate stratified, random sampling of adults aged 20-74 yrs was used to obtain a sample of 2,298 subjects (65% response), with approximately equal numbers of Chinese, Malay and Indian and in each 10 yr age group. An interviewer-administered field questionnaire was used to record symptoms of snoring and breathing disturbances during sleep witnessed by a room-mate and other personal and health-related data. The weighted point estimate (and 95% confidence interval) of the whole population prevalence of snoring was 6.8% (53-83). There were pronounced ethnic differences among Chinese, 6.2% (4.4-8.1); Malay, 8.1% (6.1-10.2) and Indian, 10.9% (85-13.4). The minimum whole population prevalence by the most restricted symptom criteria for defining sleep breathing-related disorder was 0.43% (0.05-0.8%). Similar marked ethnic differences in rates were observed using various symptom criteria. The ethnic differences in sleep breathing symptoms paralleled the differences in body mass index, neck circumference and hypertension, but statistically significant differences remained after adjustment for sex, age and these known associated factors. Marked ethnic differences in snoring and sleep breathing-related disorders were observed in Chinese, Malays and Indians in Singapore, which were only partly explained by known factors of sex, age and body habitus.
Penetration of newer quinolones in the empyema fluid
Authors: I.E. Liapakis, I. Kottakis, M.N. Tzatzarakis, A.M. Tsatsakis, M.S. Pitiakoudis, P. Ypsilantis, R.W. Light, C.E. Simopoulos, D.E. Bouros
Journal: European Respiratory Journal (2004)

The degree of penetration of newer quinolones into the pleural fluid has not been studied. The objective of the present study was to determine the degree to which moxifloxacin and levofloxacin penetrate into empyemic pleural fluid using a new rabbit model of empyema. An empyema was created via the intrapleural injection of turpentine (1 mL), followed 24 h later by instillation of 2 mL (1×10 10 ) Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, moxifloxacin and levofloxacin (25 mg·kg −1 for both, i.v. ) were administered. Antibiotic levels were determined in samples of pleural fluid and in blood collected serially over 12 h. Antibiotic levels were measured using HPLC. Each of the antibiotics penetrated well into the empyemic pleural fluid. Antibiotic penetration was the greatest for moxifloxacin (area under the curve (AUC) for pleural fluid/blood (AUC PF /AUC blood ) ratio=1.37) followed by levofloxacin (ratio=1.13). The time to equilibration between the pleural fluid and blood antibiotic levels was more rapid for moxifloxacin (3.9 h) than for levofloxacin (4.4 h). With moxifloxacin, the peak pleural fluid concentration (C max,PF ) was 2.77 µg·mL −1 and occurred at a time to maximum pleural fluid concentration ( T max,PF ) of 6 h after infusion and decreased thereafter. The peak blood concentration (C max,blood ) was 4.81 µg·mL −1 at 1 h after administration. With levofloxacin, the peak pleural fluid level (C max,PF =1.39 µg·mL −1 ) occurred at 6 h ( T max,PF =6 h) after infusion. The C max,blood was 1.88 µg·mL −1 at 1 h after administration. In conclusion, differences were found in the degree of penetration of the two quinolones into infected pleural fluid in rabbits. The clinical significance of these differences is unknown. More studies are needed to evaluate the pharmacokinetic parameters in the pleural space in humans.
Immunocytochemical localization of fibrinogen, platelet factor 4, and beta thromboglobulin in thin frozen sections of human blood platelets.
Authors: H J Sander, J W Slot, B N Bouma, P A Bolhuis, D S Pepper, J J Sixma
Journal: Journal of Clinical Investigation (1983)

Affinity-purified monospecific antibodies against human fibrinogen and the platelet-specific proteins platelet factor 4 and beta thromboglobulin were used to localize these antigens in thin and ultra-thin frozen sections of mildly fixed, washed human blood platelets. By immunofluorescent double-labeling experiments the distribution of fibrinogen was compared to that of platelet factor 4 and beta thromboglobulin. All three antigens occurred in virtually all platelets and showed and identical, dotlike distribution. For immunoelectron microscopy we used protein A-colloidal gold on ultra-thin frozen sections to visualize the specific reaction indirectly. The staining for platelet factor 4, beta thromboglobulin, and fibrinogen localized exclusively over alpha-granules of washed platelets. Within the granules, platelet factor 4 was localized preferentially in the electron dense, alpha-granule nucleoid, whereas fibrinogen was more predominant in the electron-lucent granule periphery. Beta thromboglobulin localization did not show a preferential intragranular distribution.
Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma
Authors: Mark Sausen, Rebecca J Leary, Siân Jones, Jian Wu, C Patrick Reynolds, Xueyuan Liu, Amanda Blackford, Giovanni Parmigiani, Luis A Diaz, Nickolas Papadopoulos, Bert Vogelstein, Kenneth W Kinzler, Victor E Velculescu, Michael D Hogarty
Journal: Nature Genetics (2012)
NADPH Oxidase–Derived Superoxide Anion Mediates Angiotensin II–Induced Pressor Effect via Activation of p38 Mitogen–Activated Protein Kinase in the Rostral Ventrolateral Medulla
Authors: Samuel H.H. Chan, Kuei-Sen Hsu, Chiung-Chun Huang, Ling-Lin Wang, Chen-Chun Ou, Julie Y.H. Chan
Journal: Circulation Research (2005)

The rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons are located, is a central site via which angiotensin II (Ang II) elicits its pressor effect. We tested the hypothesis that NADPH oxidase-derived superoxide anion (O 2 ·− ) in the RVLM mediates Ang II–induced pressor response via activation of mitogen-activated protein kinase (MAPK) signaling pathways. Bilateral microinjection of Ang II into the RVLM resulted in an angiotensin subtype 1 (AT 1 ) receptor-dependent phosphorylation of p38 MAPK and extracellular signal-regulated protein kinase (ERK)1/2, but not stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK), in the ventrolateral medulla. The Ang II–induced p38 MAPK or ERK1/2 phosphorylation was attenuated by application into the RVLM of a NADPH oxidase inhibitor, diphenyleneiodonium chloride (DPI), an antisense oligonucleotide that targets against p22phox or p47phox subunit of NADPH oxidase mRNA, or the superoxide dismutase mimetic tempol. DPI or antisense p22phox or p47phox oligonucleotide treatment also attenuated the AT 1 receptor-dependent increase in O 2 ·− production in the ventrolateral medulla elicited by Ang II at the RVLM. Functionally, Ang II–elicited pressor response in the RVLM was attenuated by DPI, tempol, or a p38 MAPK inhibitor, SB203580. The AT 1 receptor-mediated enhancement of the frequency of glutamate-sensitive spontaneous excitatory postsynaptic currents induced by Ang II in RVLM neurons was also abolished by SB203580. These results suggest that NADPH oxidase-derived O 2 ·− underlies the activation of p38 MAPK or ERK1/2 by Ang II in the ventrolateral medulla. Furthermore, the p38 MAPK signaling pathway may mediate Ang II–induced pressor response via enhancement of presynaptic release of glutamate to RVLM neurons.
The Impact of the Austronesian Expansion: Evidence from mtDNA and Y Chromosome Diversity in the Admiralty Islands of Melanesia
Authors: M. Kayser, Y. Choi, M. van Oven, S. Mona, S. Brauer, R. J. Trent, D. Suarkia, W. Schiefenhovel, M. Stoneking
Journal: Molecular Biology and Evolution (2008)

The genetic ancestry of Polynesians can be traced to both Asia and Melanesia, which presumably reflects admixture occurring between incoming Austronesians and resident non-Austronesians in Melanesia before the subsequent occupation of the greater Pacific; however, the genetic impact of the Austronesian expansion to Melanesia remains largely unknown. We therefore studied the diversity of nonrecombining Y chromosomal (NRY) and mitochondrial (mt) DNA in the Admiralty Islands, located north of mainland Papua New Guinea, and updated our previous data from Asia, Melanesia, and Polynesia with new NRY markers. The Admiralties are occupied today solely by Austronesian-speaking groups, but their human settlement history goes back 20,000 years prior to the arrival of Austronesians about 3,400 years ago. On the Admiralties, we found substantial mtDNA and NRY variation of both Austronesian and non-Austronesian origins, with higher frequencies of Asian mtDNA and Melanesian NRY haplogroups, similar to previous findings in Polynesia and perhaps as a consequence of Austronesian matrilocality. Thus, the Austronesian language replacement on the Admiralties (and elsewhere in Island Melanesia and coastal New Guinea) was accompanied by an incomplete genetic replacement that is more associated with mtDNA than with NRY diversity. These results provide further support for the “Slow Boat” model of Polynesian origins, according to which Polynesian ancestors originated from East Asia but genetically mixed with Melanesians before colonizing the Pacific. We also observed that non-Austronesian groups of coastal New Guinea and Island Melanesia had significantly higher frequencies of Asian mtDNA haplogroups than of Asian NRY haplogroups, suggesting sex-biased admixture perhaps as a consequence of non-Austronesian patrilocality. We additionally found that the predominant NRY haplogroup of Asian origin in the Admiralties (O-M110) likely originated in Taiwan, thus providing the first direct Y chromosome evidence for a Taiwanese origin of the Austronesian expansion. Furthermore, we identified a NRY haplogroup (K-P79, also found on the Admiralties) in Polynesians that most likely arose in the Bismarck Archipelago, providing the first direct link between northern Island Melanesia and Polynesia. These results significantly advance our understanding of the impact of the Austronesian expansion and human history in the Pacific region.
Osteoarthritis of the hip joint and acetabular dysplasia in women.
Authors: R W Smith, P Egger, D Coggon, M I Cawley, C Cooper
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To investigate the suggestion that osteoarthritis (OA) of the hip joint is often caused by subclinical acetabular dysplasia among elderly British women. METHODS--We examined 393 hip joints from the radiographs of a sample of women aged 60-75 years undergoing intravenous urography. Acetabular dysplasia was assessed using measurements of the centre-edge (CE) angle and acetabular depth (AD), which are both reduced in this condition. OA was assessed using an overall grade based on the Kellgren and Lawrence system and by measurement of minimum joint space (MJS). RESULTS--MJS was the more repeatable measure of OA, and showed a strong correlation with overall grade (Spearman rank correlation coefficient rs = -0.61, p &lt; 0.01). MJS was significantly negatively correlated with CE angle (Pearson correlation coefficient r = -0.25, p &lt; 0.001) and AD (r = -0.11, p &lt; 0.05). Consistent with these findings, there was a weak but significant positive correlation between overall grade of OA and one of the two measures (CE angle) of acetabular dysplasia. CONCLUSIONS--These results do not support the hypothesis that mild degrees of acetabular dysplasia account for a substantial proportion of hip OA in elderly women. Changes in hip joint geometry as a result of OA may be responsible for the weak negative association observed.
Characterization of Renal Chloride Channel (CLCN5) Mutations in Dent's Disease
Authors: KATSUSUKE YAMAMOTO, JEREMY P. D. T. COX, THOMAS FRIEDRICH, PAUL T. CHRISTIE, MARTIN BALD, PETER N. HOUTMAN, MARTA J. LAPSLEY, LUDWIG PATZER, MICHEL TSIMARATOS, WILLIAM G VAN'T HOFF, KANJI YAMAOKA, THOMAS J. JENTSCH, RAJESH V. THAKKER
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Dent's disease is an X-linked renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal failure. The disease is caused by mutations in a renal chloride channel gene, CLCN5, which encodes a 746 amino acid protein (CLC-5), with 12 to 13 transmembrane domains. In this study, an additional six unrelated patients with Dent's disease were identified and investigated for CLCN5 mutations by DNA sequence analysis of the 11 coding exons of CLCN5. This revealed six mutations: four frameshift deletions involving codons 392, 394, 658, and 728, one nonsense mutation (Tyr617Stop), and an A to T transversion at codon 601 that would result in either a missense mutation (Asp601Val) or creation of a novel donor splice site. These mutations were confirmed by restriction endonuclease or sequence-specific oligonucleotide hybridization analysis and were not common polymorphisms. The frameshift deletions and nonsense mutation predict truncated and inactivated CLC-5. The effects of the putative missense Asp601Val mutant CLC-5 were assessed by heterologous expression in Xenopus oocytes, and this revealed a chloride conductance that was similar to that observed for wild-type CLC-5. However, an analysis of the mutant CLCN5 transcripts revealed utilization of the novel donor splice site, resulting in a truncated CLC-5. Thus, all of the six mutations are likely to result in truncated CLC-5 and a loss of function, and these findings expand the spectrum of CLCN5 mutations associated with Dent's disease.
Large-Scale Analysis of Plasmid Relationships through Gene-Sharing Networks
Authors: M. Tamminen, M. Virta, R. Fani, M. Fondi
Journal: Molecular Biology and Evolution (2011)

Plasmids are vessels of genetic exchange in microbial communities. They are known to transfer between different host organisms and acquire diverse genetic elements from chromosomes and/or other plasmids. Therefore, they constitute an important element in microbial evolution by rapidly disseminating various genetic properties among different communities. A paradigmatic example of this is the dissemination of antibiotic resistance (AR) genes that has resulted in the emergence of multiresistant pathogenic bacterial strains. To globally analyze the evolutionary dynamics of plasmids, we built a large graph in which 2,343 plasmids (nodes) are connected according to the proteins shared by each other. The analysis of this gene-sharing network revealed an overall coherence between network clustering and the phylogenetic classes of the corresponding microorganisms, likely resulting from genetic barriers to horizontal gene transfer between distant phylogenetic groups. Habitat was not a crucial factor in clustering as plasmids from organisms inhabiting different environments were often found embedded in the same cluster. Analyses of network metrics revealed a statistically significant correlation between plasmid mobility and their centrality within the network, providing support to the observation that mobile plasmids are particularly important in spreading genes in microbial communities. Finally, our study reveals an extensive (and previously undescribed) sharing of AR genes between Actinobacteria and Gammaproteobacteria, suggesting that the former might represent an important reservoir of AR genes for the latter.
Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma: a safety report
Authors: A.F.C. Okines, R.E. Langley, L.C. Thompson, S.P. Stenning, L. Stevenson, S. Falk, M. Seymour, F. Coxon, G.W. Middleton, D. Smith, L. Evans, S. Slater, J. Waters, D. Ford, M. Hall, T.J. Iveson, R.D. Petty, C. Plummer, W.H. Allum, J.M. Blazeby, M. Griffin, D. Cunningham
Journal: Annals of Oncology (2012)
Disseminated cutaneous leishmaniasis after visceral disease in a patient with AIDS
Authors: Leonardo Calza, Antonietta D'Antuono, Ginevra Marinacci, Roberto Manfredi, Vincenzo Colangeli, Beatrice Passarini, Roberto Orioli, Ornella Varoli, Francesco Chiodo
Journal: Journal of the American Academy of Dermatology (2004)
Overview of Nomenclature of Nuclear Receptors
Authors: Pierre Germain, Bart Staels, Catherine Dacquet, Michael Spedding, Vincent Laudet
Journal: Pharmacological Reviews (2006)

Nuclear receptor pharmacology has, to a certain extent, led the way, compared with other receptor systems, in the appreciation that ligands may exert very diverse pharmacology, based on their individual chemical structure and the allosteric changes induced in the receptor/accessory protein complex. This can lead to very selective pharmacological effects, which may not necessarily be predicted from the experience with other agonists/partial agonists/antagonists. If this is the case, then drug discovery may be back to drug-specific pharmacology (where each drug may have an original profile), rather than specific-drug pharmacology (where agents specific for a receptor have a distinct profile). As functional selectivity is indeed a crucial mechanism to be considered when going through the drug discovery development process, then initial screens using reconstituted systems may not show the appropriate pharmacology, simply because the required stoichiometry of corepressors and coactivators may not be present to select the best compounds; therefore, multiple effector systems are necessary to screen for differential activation, and, even then, screening with in vivo pathophysiological models may ultimately be required for the selection process—a massive but necessary task for pharmacologists. Thus, the characterization of nuclear receptors and their associated proteins and the ligands that interact with them will remain a challenge to pharmacologists.
A HEMOLYTIC SYSTEM ASSOCIATED WITH ENTERITIS IN RABBITS
Authors: Robert S. Evans, Margaret Bingham, Russell S. Weiser
Journal: The Journal of Experimental Medicine (1963)

A disease characterized by frequent association of enteritis and polyagglutinable cells often develops in weanling rabbits. The red cell lesion renders the cells susceptible to agglutination and hemolysis in normal rabbit sera. The degree of red cell abnormality varies among different animals and disappears when the animals recover. The abnormality of the red cells responsible for their polyagglutinability and susceptibility to hemolysis was resistant to the action of trypsin or papain and persisted in heated stroma preparations derived from polyagglutinable cells. The factors necessary for agglutination and hemolysis of the polyagglutinable cells are present in normal rabbit sera but are lacking in the sera of affected rabbits. These factors returned to normal levels as the polyagglutinable cell lesion disappeared. The sera of rabbits with polyagglutinable cells contained normal levels of complement and properdin. Whereas the agglutinating factor in normal sera is heat-stable at 56 degrees C for 30 minutes, the hemolytic factor is heat labile. The hemolytic factor is apparently distinct from complement and properdin since it was adsorbed from normal rabbit serum by zymosan or by polyagglutinable cells at 0 degrees C. However, complement was fixed when normal rabbit serum was reacted with stroma from polyagglutinable cells. Hemolysis of polyagglutinable cells by normal rabbit serum at 25 degrees C was inhibited by preliminary incubation of the mixture at 0 degrees C prior to incubation at 25 degrees C. Evidence was obtained which indicated that this inhibition was due to progression of a reaction involving Ca(++) independent of a reaction involving Mg(++).