tbuckley/cabot-search huggingface dataset:
CHARACTERIZATION OF THE "REACTANT" (GAMMA GLOBULIN FACTOR) IN THE F II PRECIPITIN REACTION AND THE F II TANNED SHEEP CELL AGGLUTINATION TEST
Authors: Charles L. Christian
Journal: The Journal of Experimental Medicine (1958)

The material in gamma globulin ("reactant") which reacts with rheumatoid sera in the F II precipitin and F II tanned sheep cell agglutination tests was concentrated by precipitation with sodium sulfate. The concentrated "reactant" appeared to consist of polydispersed molecular aggregates of gamma globulin with s(20) constants as high as 40, as well as the previously described inhomogeneous aggregated material. Aggregated gamma globulin precipitated readily with most rheumatoid sera regardless of the reaction volume, and in low concentration inhibited the F II tanned sheep cell agglutination reaction and sensitized tanned erythrocytes to the agglutinating action of a positive rheumatoid serum. On the other hand, non-aggregated gamma globulin (7S) did not precipitate with rheumatoid sera and in low concentration did not inhibit the F II tanned sheep cell agglutination reaction, or sensitize tanned erythrocytes. Non-aggregated gamma globulin in large excess inhibited the precipitin reaction of aggregated gamma globulin with "rheumatoid factor," and accounted for the characteristic shape of the whole F II precipitin curves and the volume effect described by Vaughan (relation of increased precipitate yield relative to the reaction volume in whole F II precipitin studies). In serological systems other than the F II tanned sheep cell and F II precipitin reactions, the sensitization involves an antigen-antibody combination; i.e., sheep erythrocyte plus hemolysin in the sensitized sheep cell test, and egg albumin plus anti egg albumin in the absorption experiments with specific precipitates. The aggregation of gamma globulin that was essential for sensitization in the F II tanned sheep cell and F II precipitin tests may have simulated the aggregation of antibody gamma globulin that occurs with antigen-antibody union. The present information has been incorporated into a schematic hypothesis for the basis of the rheumatoid serological reactions.
STUDIES ON EXPERIMENTAL PNEUMONIA
Authors: Francis G. Blake, Russell L. Cecil
Journal: The Journal of Experimental Medicine (1920)

Spontaneous pneumonia occurred to a considerable extent among stock monkeys at the Army Medical School. This pneumonia occurred chiefly in the form of an epidemic outbreak shortly after the arrival of a large shipment of monkeys, and was shown to be due in large part to transmission of infection from monkey to monkey, either directly or indirectly. That spread of the epidemic was facilitated by overcrowding was indicated by the fact that in a subsequent shipment of monkeys, which were kept in pairs in separate cages and were not allowed to come into contact with the monkeys among which the epidemic occurred, no cases of spontaneous pneumonia developed. The close analogy between the epidemic of lobar pneumonia that occurred among the monkeys and similar epidemics of lobar pneumonia that occurred during the war among certain groups of newly drafted troops shortly after their arrival at camp is very striking, and would seem to indicate that pneumococcus pneumonia may become an epidemic disease among groups of susceptible individuals when they are assembled under conditions that facilitate the ready transfer of infection from individual to individual. Bacteriological examination showed the spontaneous pneumonia to be due in the great majority of cases to infection with Pneumococcus Type IV. Immunological classification of the strains of pneurnococci by cross-agglutination tests showed that the majority fell into two biological groups. Two cases were apparently caused by Streptococcus haemolyticus, two by Streptococcus viridans. The clinical course of spontaneous pneumococcus pneumonia in monkeys was characterized by sudden onset, high sustained temperature, leucocytosis, rapid respiration with expiratory grunt, cough, physical signs of consolidation, invasion of the blood by pneurnococci, and termination in death or recovery by crisis about the 7th to 9th day. In a few instances the disease was complicated by acute fibrinopurulent pericarditis, by empyema, and by purulent meningitis. It was, therefore, clinically identical with lobar pneumonia experimentally produced in monkeys and with lobar pneumonia in man. Study of the pathology of spontaneous pneumococcus pneumonia in monkeys showed that it presented the characteristic picture of lobar pneumonia, both macroscopically and microscopically, and was in all respects comparable with the pathology of lobar pneumonia experimentally produced in monkeys and of lobar pneumonia in man.
Pharmacogenetics and ethnically targeted therapies
Authors: Taslin Rahemtulla, Raj Bhopal
Journal: BMJ (2005)

New drug BiDil marks the return of biology to the debate about race and ethnicity 

I n modern conceptions of race and ethnicity, biology has been relegated to a minor underlying factor.1 Instead, these concepts have been cast as largely social constructions.2 For example, race traditionally distinguishes between groups according to a mixture of physical characteristics (including skin colour), which reflect ancestry and hence biology. A modern conception of race would place the emphasis on a common social and political heritage. Similarly, ethnicity puts emphasis on distinguishing between groups by using a mixture of cultural factors, including language and religion.2 Recent developments in pharmacogenetics, however, renew the historical emphasis on biology in concepts of race and ethnicity. Pharmacogeneticists examine whether different responses to drug treatment may be attributable to genetic differences. They are focusing on race and ethnicity as a means to this end. A recent international conference, the 8th world congress on clinical pharmacology and therapeutics, in Brisbane, Australia, had an afternoon on ethnopharmacology, showing how seriously this new subject is being taken.3 …
Increased expression of apoptosis signalling receptors by alveolar macrophages in sarcoidosis
Authors: H Dai, J Guzman, U Costabel
Journal: European Respiratory Journal (1999)

The Fas receptor (FasR) and the tumour necrosis factor (TNF) receptor 55/60 kDa (TNFR1) are recognized as apoptosis signalling receptors. They are known to be expressed by lymphocytes in association with immune regulation and immunological disorders. This study aimed to investigate the expression of FasR and TNFR1 by alveolar macrophages (AM) in patients with sarcoidosis. Bronchoalveolar lavage (BAL) was performed in 12 patients with active sarcoidosis and 11 control subjects. BAL cells were characterized by monoclonal antibodies using a peroxidase-antiperoxidase method. Both FasR and TNFR1 were expressed on a higher percentage of AM in sarcoidosis with respect to control subjects (mean +/-sem 40.8+/-3.1% versus 14.9+/-1.7%, p&lt;0.001 and 61.9+/-3.3% versus 23.1+/-4.1%, p&lt;0.001, respectively). There was a close relationship between the expression of FasR and TNFR1 on AM (r = 0.86, p&lt;0.001). The percentages of FasR+ AM and TNFR1+ AM were in direct proportion to the percentage of BAL lymphocytes (r = 0.75 and 0.84), the CD4/CD8 ratio (r = 0.78 and 0.78), and the percentage of the CD14+ AM subset (r = 0.77 and 0.87), p&lt;0.001 for all correlations. This study indicates that alveolar macrophages expressing apoptotic receptors are increased in patients with active sarcoidosis. Further studies are required to determine whether these alveolar macrophages from patients with sarcoidosis undergo apoptosis more readily than those from control subjects.
eNOS Deficiency Acts through Endothelin to Aggravate sFlt-1–Induced Pre-Eclampsia–Like Phenotype
Authors: Feng Li, John R. Hagaman, Hyung-Suk Kim, Nobuyo Maeda, J. Charles Jennette, James E. Faber, S. Ananth Karumanchi, Oliver Smithies, Nobuyuki Takahashi
Journal: Journal of the American Society of Nephrology (2012)

Excess soluble fms-like tyrosine kinase 1 (sFlt-1) of vascular endothelial growth factor receptor 1 secreted from the placenta causes pre-eclampsia–like features by antagonizing vascular endothelial growth factor signaling, which can lead to reduced endothelial nitric oxide synthase (eNOS) activity; the effect of this concomitant decrease in eNOS activity is unknown. We tested whether the decrease in nitric oxide occurring in female mice lacking eNOS aggravates the pre-eclampsia–like phenotype induced by increased sFlt-1. Untreated eNOS-deficient female mice had higher BP than wild-type mice. Adenovirus-mediated overexpression of sFlt-1 increased systolic BP by approximately 27 mmHg and led to severe loss of fenestration of glomerular capillary endothelial cells in both eNOS-deficient and wild-type mice. However, only the eNOS-deficient sFlt-1 mice exhibited severe foot process effacement. Compared with wild-type sFlt-1 mice, eNOS-deficient sFlt-1 mice also showed markedly higher urinary albumin excretion (467±74 versus 174±23 μg/d), lower creatinine clearance (126±29 versus 452±63 μl/min), and more severe endotheliosis. Expression of preproendothelin-1 (ET-1) and its ETA receptor in the kidney was higher in eNOS-deficient sFlt-1 mice than in wild-type sFlt-1 mice. Furthermore, the selective ETA receptor antagonist ambrisentan attenuated the increases in BP and urinary albumin excretion and ameliorated endotheliosis in both wild-type and eNOS-deficient sFlt-1 mice. Ambrisentan improved creatinine clearance and podocyte effacement in eNOS-deficient sFlt-1 mice. In conclusion, reduced maternal eNOS/nitric oxide exacerbates the sFlt1-related pre-eclampsia–like phenotype through activation of the endothelin system.
Inhibition of platelet function by an aspirin-insensitive endothelial cell ADPase. Thromboregulation by endothelial cells.
Authors: A J Marcus, L B Safier, K A Hajjar, H L Ullman, N Islam, M J Broekman, A M Eiroa
Journal: Journal of Clinical Investigation (1991)

We previously reported that platelets become unresponsive to agonists when stimulated in combined suspension with aspirin-treated human umbilical vein endothelial cells. Inhibition occurred concomitant with metabolism of platelet-derived endoperoxides to prostacyclin by endothelial cells. We now demonstrate that if aspirin-treated platelets which fully respond to appropriate doses of agonists are exposed to aspirin-treated endothelial cells, they remain unresponsive despite absence of prostacyclin. Platelet inhibition is due in large part to ecto-ADPase activity on the endothelial cells. This was established by incubating aspirin-treated endothelial cells with 14C-ADP. Radio-thin layer chromatography and aggregometry demonstrated that 14C-ADP and induction of platelet activation decreased rapidly and concurrently. AMP accumulated transiently, was further metabolized to adenosine, and deaminated to inosine. The apparent Km of the endothelial cell ADPase was 33-42 microM and the Vmax 17-43 nmol/min per 10(6) cells, values in the range of antithrombotic potential. Thus, at least three complementary systems in human endothelial cells control platelet responsiveness: a cell-associated, aspirin-insensitive ADPase which functions in parallel with fluid phase autacoids such as the aspirin-inhibitable eicosanoids, and the aspirin-insensitive endothelium-derived relaxing factor.
A biography of the chondrocyte
Authors: P A Simkin
Journal: Annals of the Rheumatic Diseases (2008)

Significant gaps persist in our understanding of chondrocyte biology. We do not know when, how, or even whether these cells are replenished throughout the normal, human life span. We are taught that as much as 90% of the cartilage is "metabolically inert" interterritorial matrix, but we do not know how this substance is regularly replaced (as it is known to be) by the distant chondrocytes, We recognise that the "tidemark" is the most conspicuous histological feature within cartilage, but we do not understand why that layer stains with haematoxylin or what that may imply for the biology of the tissue. These, and other issues may be clarified if the lifetime of each chondrocyte begins as a mesenchymal stem cell at the articular margin, plays out over years on an arcing trajectory along collagenous guidelines, and ends as an extracellular deposit of intracellular remains at the interface between uncalcified and calcified cartilage. This hypothesis is presented here, and some of its potential implications are considered.
Compensatory Mutations Restore Fitness during the Evolution of Dihydrofolate Reductase
Authors: K. M. Brown, M. S. Costanzo, W. Xu, S. Roy, E. R. Lozovsky, D. L. Hartl
Journal: Molecular Biology and Evolution (2010)

Whether a trade-off exists between robustness and evolvability is an important issue for protein evolution. Although traditional viewpoints have assumed that existing functions must be compromised by the evolution of novel activities, recent research has suggested that existing phenotypes can be robust to the evolution of novel protein functions. Enzymes that are targets of antibiotics that are competitive inhibitors must evolve decreased drug affinity while maintaining their function and sustaining growth. Utilizing a transgenic Saccharomyces cerevisiae model expressing the dihydrofolate reductase (DHFR) enzyme from the malarial parasite Plasmodium falciparum, we examine the robustness of growth rate to drug-resistance mutations. We assay the growth rate and resistance of all 48 combinations of 6 DHFR point mutations associated with increased drug resistance in field isolates of the parasite. We observe no consistent relationship between growth rate and resistance phenotypes among the DHFR alleles. The three evolutionary pathways that dominate DHFR evolution show that mutations with increased resistance can compensate for initial declines in growth rate from previously acquired mutations. In other words, resistance mutations that occur later in evolutionary trajectories can compensate for the fitness consequences of earlier mutations. Our results suggest that high levels of resistance may be selected for without necessarily jeopardizing overall fitness.
Effects of Esophageal Constriction on Benzo[ a lpyrene Carcinogenesis in Hamster Esophagus and Forestomach
Authors: Lucia J. Dunham, Ray H. Sheets
Journal: JNCI Journal of the National Cancer Institute (1974)

To constrict the lumen of the hamster esophagus, polyethylene cuffs were surgically implanted around the esophagus just above its junction with the forestomach. This procedure resulted in atrophy of epithelium at the level of the cuff and proximal dilatation of the esophagus with hypertrophy of muscle. The benzo[a]pyrene (BP) in dimethyl sulfoxide (DMSO) vehicle was instilled twice weekly for 5 weeks in the esophagus of hamsters with and without the constricting cuffs, and eventually papille;matous lesions and atypias developed in the esophagus and papillomas in the forestomach of some of the hamsters that survived to ages over 9 months. Though lesions developed in the esophagus and forestomach in hamsters in both groups treated with BP, there were differences in the types of lesions and in survival times. In the esophagus, a papillary carcinoma, papillomatosis, and an area of cellular atypia developed in 3 of 8 hamsters with constricted esophagus; a papilloma and 5 instances of cell atypia developed in 6 of 18 hamsters with non constricted esophagus. The ages of hamsters with esophageal lesions in the constricted group averaged 4.5 months less than in the nonconstricted group. In the forestomach, there were fewer papillomas per affected hamster in the constricted group, even though these hamsters were 4 months older than those with gastric papillomas in the nonconstricted group. Gastric papillomas that had progressed to carcinoma were found only in hamsters without constriction of the esophagus.
Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients
Authors: Philip F. Halloran, Jessica Chang, Konrad Famulski, Luis G. Hidalgo, Israel D.R. Salazar, Maribel Merino Lopez, Arthur Matas, Michael Picton, Declan de Freitas, Jonathan Bromberg, Daniel Serón, Joana Sellarés, Gunilla Einecke, Jeff Reeve
Journal: Journal of the American Society of Nephrology (2014)

The prevalent renal transplant population presents an opportunity to observe the adaptive changes in the alloimmune response over time, but such studies have been limited by uncertainties in the conventional biopsy diagnosis of T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). To circumvent these limitations, we used microarrays and conventional methods to investigate rejection in 703 unselected biopsies taken 3 days to 35 years post-transplant from North American and European centers. Using conventional methods, we diagnosed rejection in 205 biopsy specimens (28%): 67 pure TCMR, 110 pure ABMR, and 28 mixed (89 designated borderline). Using microarrays, we diagnosed rejection in 228 biopsy specimens (32%): 76 pure TCMR, 124 pure ABMR, and 28 mixed (no borderline). Molecular assessment confirmed most conventional diagnoses (agreement was 90% for TCMR and 83% for ABMR) but revealed some errors, particularly in mixed rejection, and improved prediction of failure. ABMR was strongly associated with increased graft loss, but TCMR was not. ABMR became common in biopsy specimens obtained >1 year post-transplant and continued to appear in all subsequent intervals. TCMR was common early but progressively disappeared over time. In 108 biopsy specimens obtained 10.2-35 years post-transplant, TCMR defined by molecular and conventional features was never observed. We conclude that the main cause of kidney transplant failure is ABMR, which can present even decades after transplantation. In contrast, TCMR disappears by 10 years post-transplant, implying that a state of partial adaptive tolerance emerges over time in the kidney transplant population.
FOXQ1 Regulates Epithelial-Mesenchymal Transition in Human Cancers
Authors: Yuanyuan Qiao, Xia Jiang, Shuet Theng Lee, R.K. Murthy Karuturi, Shing Chuan Hooi, Qiang Yu
Journal: Cancer Research (2011)

Epithelial-mesenchymal transition (EMT) in cancer cells plays a pivotal role in determining metastatic prowess, but knowledge of EMT regulation remains incomplete. In this study, we defined a critical functional role for the Forkhead transcription factor FOXQ1 in regulating EMT in breast cancer cells. FOXQ1 expression was correlated with high-grade basal-like breast cancers and was associated with poor clinical outcomes. RNAi-mediated suppression of FOXQ1 expression in highly invasive human breast cancer cells reversed EMT, reduced invasive ability, and alleviated other aggressive cancer phenotypes manifested in 3-dimensional Matrigel (BD Biosciences) culture. Conversely, enforced expression of FOXQ1 in differentiated human mammary epithelial cells (HMLER) or epithelial cancer cell lines provoked an epithelial to mesenchymal morphologic change, gain of stem cell-like properties, and acquisition of resistance to chemotherapy-induced apoptosis. Mechanistic investigations revealed that FOXQ1-induced EMT was associated with transcriptional inactivation of the epithelial regulator E-cadherin (CDH1). Our findings define a key role for FOXQ1 in regulating EMT and aggressiveness in human cancer.
Intrinsic risk factors for sport injuries in female volleyball
Authors: T Sattler
Journal: British Journal of Sports Medicine (2011)

Background/objective To investigate the incidence and injury mechanism as well as intrinsic risk factors for acute sports injuries in female volleyball. Design Prospective epidemiological study. Setting and participants 174 female volleyball players from Slovenian Divisions I and II were prospectively monitored during 2007–2008 season. Methods All injuries were prospectively documented by team coaches. Prior to the season all players underwent the following tests: anthropometry, sit and reach test, isokinetic strength testing of the knee and shoulder, postural stability testing and vertical jump testing. Main outcome measure was injury incidence; binary logistic regression was used afterwards in order to evaluate the role of different parameters from functional testing on injury occurrence. Results The overall incidence of injuries for the females was 0.35±0.19 per 1000 h of volleyball played. The incidence of injuries in a game situation was higher than in practice (2.10±1.06 vs 0.42±0.24) The most frequent injury was acute ankle sprain 1.45 (1.98), followed by knee injury 0.69 (1.34). Majority of injuries occurred during the competition season (81.4%), in the middle of training (25.58%) or during a game (25.58%). Most injuries occurred during landing (41.4%). Risk factor analysis revealed that previous injury is an important risk factor for acute knee injuries and ankle sprains. Low hamstring quadriceps ratio was related with ankle sprains, while quadriceps strength asymmetry was related to acute knee injuries. Conclusions The results of our study suggest that isokinetic strength testing in previously injured female volleyball players could identify players with increased risk for acute knee injuries and ankle sprains.
Endogenous glucose production is inhibited by the adipose-derived protein Acrp30
Authors: Terry P. Combs, Anders H. Berg, Silvana Obici, Philipp E. Scherer, Luciano Rossetti
Journal: Journal of Clinical Investigation (2001)

Intraperitoneal injection of purified recombinant Acrp30 lowers glucose levels in mice. To gain insight into the mechanism(s) of this hypoglycemic effect, purified recombinant Acrp30 was infused in conscious mice during a pancreatic euglycemic clamp. In the presence of physiological hyperinsulinemia, this treatment increased circulating Acrp30 levels by approximately twofold and stimulated glucose metabolism. The effect of Acrp30 on in vivo insulin action was completely accounted for by a 65% reduction in the rate of glucose production. Similarly, glucose flux through glucose-6-phosphatase (G6Pase) decreased with Acrp30, whereas the activity of the direct pathway of glucose-6-phosphate biosynthesis, an index of hepatic glucose phosphorylation, increased significantly. Acrp30 did not affect the rates of glucose uptake, glycolysis, or glycogen synthesis. These results indicate that an acute increase in circulating Acrp30 levels lowers hepatic glucose production without affecting peripheral glucose uptake. Hepatic expression of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase and G6Pase mRNAs was reduced by more than 50% following Acrp30 infusion compared with vehicle infusion. Thus, a moderate rise in circulating levels of the adipose-derived protein Acrp30 inhibits both the expression of hepatic gluconeogenic enzymes and the rate of endogenous glucose production.