tbuckley/cabot-search huggingface dataset:
THE ORIGIN OF CELL SURFACE IMMUNOGLOBULIN OF MARROW-DERIVED AND THYMUS-DERIVED LYMPHOCYTES OF THE RAT
Authors: Simon V. Hunt, Alan F. Williams
Journal: The Journal of Experimental Medicine (1974)

The origin of immunoglobulin on the surface of TDL in the rat has been studied by comparing the binding of purified alloantibodies recognizing the Ig-1a allotype of rat light chain, with that of rabbit antirat Fab antibodies. Both reagents labeled all TDL from rats of the DA strain (Ig-1a) with two categories of cells being detected; one binding 100–2,000 molecules of antibody, the other 10,000–100,000 molecules. These categories were likely to be synonomous with T and B cells, respectively. The [125I]antiallotype antibodies did not bind to TDL from rats of the PVG/c strain (Ig-1b). When the binding to TDL from (PVG/c x DA)F1 animals was studied it was found that allelic exclusion occurred in the heavily labeled cells, but not in the lightly labeled ones. Furthermore, when lymphocytes of one allotype were transferred to irradiated recipients of the opposite allotype and recovered from the TDL or spleen of the recipient 20–30 h later, the immunoglobulin on heavily labeled cells was of the donor type, while that of lightly labeled ones bore the recipient marker. Thus heavily labeled cells (B lymphocytes) had synthesized their own immunoglobulin while lightly labeled cells (T lymphocytes) had acquired theirs passively by adsorption. The class of immunoglobulin on lightly labeled cells was also studied and it was found that [125I]anti-IgM antibodies bound to an extent approaching the [125I]anti-Fab binding, while [125I]anti-IgG2a+2b antibodies gave much less binding.
Toll‐like receptors and adaptor molecules in liver disease: Update
Authors: Ekihiro Seki, David A. Brenner
Journal: Hepatology (2008)

Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen-associated molecular patterns and signal through adaptor molecules, myeloid differentiation factor 88 (MyD88), Toll/IL-1 receptor domain containing adaptor protein (TIRAP), Toll/IL-1 receptor domain containing adaptor inducing interferon-β (TRIF), and TRIF-related adaptor molecule (TRAM) to activate transcription factors, nuclear factor (NF)-κB, activator protein 1 (AP-1), and interferon regulatory factors (IRFs) leading to the initiation of innate immunity. This system promptly initiates host defenses against invading microorganisms. Endogenous TLR ligands such as the products from dying cells may also engage with TLRs as damage-associated molecular patterns. Although Kupffer cells are considered the primary cells to respond to pathogen associated molecular patterns in the liver, recent studies provide evidence of TLR signaling in hepatic nonimmune cell populations, including hepatocytes, biliary epithelial cells, endothelial cells, and hepatic stellate cells. This review highlights advances in TLR signaling in the liver, the role of TLRs in the individual hepatic cell populations, and the implication of TLR signaling in acute and chronic liver diseases. We further discuss recent advances regarding cytosolic pattern recognition receptors, RNA helicases that represents a new concept in chronic hepatitis C virus infection. (HEPATOLOGY 2008.)
PERSISTENCE OF STREPTOCOCCAL GROUP A ANTIBODY IN PATIENTS WITH RHEUMATIC VALVULAR DISEASE
Authors: Burton A. Dudding, Elia M. Ayoub
Journal: The Journal of Experimental Medicine (1968)

Antibody levels to streptococcal Group A and A-variant carbohydrates were determined using a radioactive immune precipitation technique on patients with rheumatic fever, with and without valvular disease, on patients with post-streptococcal acute glomerulonephritis, and on age-matched controls. During the acute phase of the above illness, the means of the antibody levels to both carbohydrate antigens were equally elevated and were significantly higher than the normal controls. When Group A antibody levels were determined on sera obtained at intervals of 5-12 months and 1-5 yr after the acute illness) it was found that the antibody levels declined within the normal range at the 5-12 month interval in patients with glomerulonephritis as well as in patients with rheumatic fever in whom no valvular involvement had complicated the disease, i.e., patients with pure Sydenham's chorea. However, in patients with rheumatic valvulitis, who had been on penicillin prophylaxis after the last acute episode, the A antibody level showed little decline from the level obtained during the acute illness. The elevated antibody level in patients with rheumatic valvulitis, including patients with Sydenham's chorea with valvulitis, persisted for periods of at least 1 yr and up to 20 yr after the last acute attack. The pattern of the decline of the antibody levels to the A-variant carbohydrate as well as of the antibody titers to the other streptococcal antigens tested, ASO and anti-DNase B, was similar in all patients studied regardless of the presence of valvular disease. These findings suggest that prolonged persistence of the Group A antibody is a phenomenon peculiar to patients with rheumatic valvular disease. Whether this persistence is involved in the pathogenesis or is an outcome of the valvular disease remains to be determined.
Active convulsive epilepsy in a rural district of Kenya: a study of prevalence and possible risk factors
Authors: Tansy Edwards, Anthony G Scott, Gilbert Munyoki, Victor Mung'ala Odera, Edward Chengo, Evasius Bauni, Thomas Kwasa, Ley W Sander, Brian G Neville, Charles R Newton
Journal: The Lancet Neurology (2008)
Activatable Magnetic Resonance Imaging Agent Reports Myeloperoxidase Activity in Healing Infarcts and Noninvasively Detects the Antiinflammatory Effects of Atorvastatin on Ischemia-Reperfusion Injury
Authors: Matthias Nahrendorf, David Sosnovik, John W. Chen, Peter Panizzi, Jose-Luiz Figueiredo, Elena Aikawa, Peter Libby, Filip K. Swirski, Ralph Weissleder
Journal: Circulation (2008)

Background— Ischemic injury of the myocardium causes timed recruitment of neutrophils and monocytes/macrophages, which produce substantial amounts of local myeloperoxidase (MPO). MPO forms reactive chlorinating species capable of inflicting oxidative stress and altering protein function by covalent modification. We have used a small-molecule, gadolinium-based activatable sensor for magnetic resonance imaging of MPO activity (MPO-Gd). MPO-Gd is first radicalized by MPO and then either spontaneously oligomerizes or binds to matrix proteins, all leading to enhanced spin-lattice relaxivity and delayed washout kinetics. We hypothesized that MPO imaging could be used to measure inflammatory responses after myocardial ischemia locally and noninvasively in a murine model. Methods and Results— We injected 0.3 mmol/kg MPO-Gd (or Gd-DTPA as control) and performed magnetic resonance imaging up to 120 minutes later in mice 2 days after myocardial infarction. The contrast-to-noise ratio (infarct versus septum) after Gd-DTPA injection peaked at 10 minutes and returned to preinjection values at 60 minutes. After injection of MPO-Gd, the contrast-to-noise ratio peaked later and was higher than Gd-DTPA (40.8±10.4 versus 10.5±0.2; P &lt;0.05). MPO imaging was validated by magnetic resonance imaging of MPO −/− mice and correlated well with immunoreactive staining ( r 2 =0.92, P &lt;0.05), tissue activity by guaiacol assay ( r 2 =0.65, P &lt;0.001), and immunoblotting. In time course imaging, activity peaked 2 days after coronary ligation. Flow cytometry of digested infarcts detected MPO in neutrophils and monocytes/macrophages. Furthermore, serial MPO imaging accurately tracked the antiinflammatory effects of atorvastatin therapy after ischemia-reperfusion injury. Conclusions— MPO-Gd enables in vivo assessment of MPO activity in injured myocardium. This approach allows noninvasive evaluation of the inflammatory response to ischemia and has the potential to guide the development of novel cardioprotective therapies.
Delayed Versus Immediate Surgical Intervention and Prostate Cancer Outcome
Authors: Christopher Warlick, Bruce J. Trock, Patricia Landis, Jonathan I. Epstein, H. Ballentine Carter
Journal: JNCI Journal of the National Cancer Institute (2006)

For prostate cancer patients with small, lower-grade tumors, expectant management with delayed surgical intervention (active surveillance) is a rarely used therapeutic option because the opportunity for cure may be lost. We compared outcomes of 38 patients with small, lower-grade prostate cancer in an expectant management program who underwent delayed surgical intervention at a median of 26.5 months (95% confidence interval [CI] = 17 to 32 months; range = 12.0-73.0 months) after diagnosis with 150 similar patients who underwent immediate surgical intervention at a median of 3.0 months (95% CI = 2 to 4 months; range = 1.0-9.0 months) after diagnosis. Noncurable cancer was defined as adverse pathology associated with a less than 75% chance of remaining disease-free for 10 years after surgery. Noncurable cancer was diagnosed in nine (23%) of the 38 patients in the delayed intervention cohort and in 24 (16%) of the 150 men in the immediate intervention group. After adjusting for age and prostate-specific antigen (PSA) density (i.e., PSA value divided by prostate volume) in a Mantel-Haenszel analysis, the risks of noncurable cancer associated with delayed and immediate intervention did not differ statistically significantly (relative risk = 1.08, 95% CI = 0.55 to 2.12; P = .819, two-sided Cochran-Mantel-Haenszel statistic). Age, PSA, and PSA density were all statistically significantly associated with the risk of noncurable cancer (P = .030, .013, and .008, respectively; two-sided chi-square test). Thus, delayed prostate cancer surgery for patients with small, lower-grade prostate cancers does not appear to compromise curability.
Antenatal teaching of the use of seat belts in pregnancy.
Authors: M. Griffiths, M. M. Usherwood, P. W. Reginald
Journal: BMJ (1992)

Road traffic accidents are the commonest cause of blunt maternal trauma in pregnancy.'In the United Kingdom it is compulsory for motorists and passengers to wear seat belts unless they have a medical exemption certificate.Some pregnant women find seat belts uncomfortable and do not wear them, others wear them incorrectly.We recently reported two cases showing the hazards to the fetus ofill fitting restraints.2Aware that pregnant women may not know how to wear seat belts correctly, we surveyed the teaching of seat belt use in antenatal classes.
High cancer cell death in syngeneic tumors developed in host mice deficient for the stromelysin-3 matrix metalloproteinase.
Authors: Anne Boulay, Régis Masson, Marie-Pierre Chenard, Mostapha El Fahime, Lydie Cassard, Jean-Pierre Bellocq, Catherine Sautèes-Fridman, Paul Basset, Marie-Christine Rio
Journal: Cancer Research (2001)

Matrix metalloproteinases (MMPs) are extracellular enzymes. Some of them are known to be involved in tumor development and/or progression. Several cellular functions have been proposed for MMPs during malignant processes. Notably, they may be involved in tissue-remodeling processes through their ability to digest matrix components or to participate in tumor neoangiogenesis and, subsequently, in cancer cell proliferation. One of these MMPs, stromelysin-3 (ST3/MMP11), although devoid of enzymatic activity against the matrix components, is associated with human tumor progression and poor patient clinical outcome. Using several in vivo experimental models, it has been demonstrated that ST3 expression by the fibroblastic cells surrounding malignant epithelial cells promotes tumorigenesis in a paracrine manner. The present study was devoted to the identification of the cellular function underlying this ST3-induced tumor promotion using a syngeneic tumorigenesis model in mice. Our results show that ST3 exhibits a new and unexpected role for a MMP, because ST3-increased tumorigenesis does not result from increased neoangiogenesis or cancer cell proliferation but from decreased cancer cell death through apoptosis and necrosis. Thus, during malignancy, the cellular function of ST3 is to favor cancer cell survival in the stromal environment.
Minimally invasive coronary surgery: fad or future?
Authors: M. A Mariani, P. W Boonstra, J. G Grandjean
Journal: BMJ (1998)

Minimally invasive coronary surgery is a radical modification of conventional coronary artery bypass surgery and is performed through a small thoracotomy, the surgeon anastomosing the left internal mammary artery to the left anterior descending artery without the use of either cardiopulmonary bypass or cardioplegic arrest.1 2 Since its description in 1994,1 few new techniques in cardiac surgery have aroused such interest or had such a rapid diffusion. Initial enthusiasm, however, has been followed by a wave of scepticism. As the indications for minimally invasive coronary surgery become clearer it is time for a calmer apraisal.

Initial enthusiasm for the technique arose because it avoided the need for cardiopulmonary bypass3 and provided an opportunity to reduce the use of health- care resources. Inevitably there were early failures, and some investigators began to highlight …
The rabbit as an animal model for the activated factor X-antithrombin III-heparin reaction.
Authors: S N Gitel, S Wessler, V M Medina
Journal: Circulation Research (1977)

When activated factor X (Xa) inhibitory activity of serially diluted human and rabbit plasma is determined in a low salt assay, a lineare plot is obtained for human, but not for rabbit plasma. When a high salt assay is used, the dilution curves for both human and rabbit plasma are linear, and qualititive as well as quantitative differences are essentially eliminated. On Sephadex G-200 chromatography Xa inhibitory activity of human and rabbit plasma appears in two peaks. With the low salt assay the first and second peaks for human plasma contain respectively 30%, and 70% of the activity; whereas with rabbit plasma these values are greater than 95% and less than 5% of the activity. With the high salt assay the figures for human plasma are less than 5% and greater than 95%, and with rabbit plasma 65 +/- 3% and 35 +/- 3%, respectively. With the high salt system, rabbit plasma shows a continuous increase in Xa inhibitory activity with increasing heparin concentrations, similar to that obtained with human plasma. In the high salt system the relative contributions of antithrombin III to Xa neutralization in human and rabbit plasma are different. However, in experiments in which Xa inhibitory activity of antithrombin III is altered by heparin, a simple formula, Total activity (%) = 65% + 0.35 x human plasma (%), permits translation of rabbit data on the Xa-antithrombin III-heparin reaction to man. On the basis of these findings, the rabbit model can effectively be used to study the Xa-antithrombin III reaction.
Platelet-activating factor biosynthesis by cultured mesangial cells is modulated by proteinase inhibitors.
Authors: L Biancone, C Tetta, E Turello, G Montrucchio, E L Iorio, L Servillo, C Balestrieri, G Camussi
Journal: Journal of the American Society of Nephrology (1992)

Rat mesangial cells stimulated with calcium ionophore A23187 and phagocytosis were shown to produce platelet-activating factor (PAF), a mediator of inflammation and endotoxic shock. In the study presented here, the cultured human mesangial but not epithelial cells synthetized PAF not only in response to calcium ionophore A23187 and phagocytosis of immunoglobulin G-coated latex beads, but also after stimulation with cytokines such as tumor necrosis factor-alpha and interleukin-1 beta. PAF synthetized after stimulation with A23187 and to a lesser extent with phagocytosis was partially released. In contrast, PAF synthesized by stimulation with tumor necrosis factor-alpha and interleukin-1 beta remained cell associated. Experiments with labeled precursors demonstrated that PAF was synthetized via the remodeling pathway that involves the activation of phospholipase A2 and of an acetyl-coenzymeA:2-lyso-PAF acetyltransferase. Synthetic inhibitors of serine proteases as well as plasma alpha 1-proteinase inhibitor inhibited the activation of phospholipase A2 detected as release of (14C) arachidonic acid and the activation of acetyl-CoA:2-lyso-PAF acetyltransferase at concentrations 100-fold lower than those present in plasma. This raises the question about the ability of mesangial cells to synthetize PAF in vivo. However, the inhibitory effect of plasma alpha 1-proteinase inhibitor may be abrogated by oxidative inactivation due to a concomitant stimulation of mesangial cell respiratory burst or in zones of close contact among cells or matrix, which have been shown to exclude antiproteinases.
Hypoxia Increases Group IIA Phospholipase A2 Expression under Inflammatory Conditions in Rat Renal Mesangial Cells
Authors: Claudia Petry, Andrea Huwiler, Wolfgang Eberhardt, Marietta Kaszkin, Josef Pfeilschifter
Journal: Journal of the American Society of Nephrology (2005)

Hypoxia evokes a common mechanism of oxygen sensing mediated by hypoxia-inducible transcription factors (HIF) in many mammalian cells. This study investigated the effect of hypoxia on group-IIA secretory phospholipase A(2) (sPLA(2)-IIA) expression in renal mesangial cells. Stimulation of cells with IL-1beta under normoxic conditions (21% O(2)) is known to induce expression and secretion of the group sPLA(2)-IIA. This induction is further enhanced by constantly reducing the O(2) concentration to 1% O(2), and is accompanied by increased sPLA(2) activity. To see whether hypoxia potentiates IL-1beta-induced sPLA(2)-IIA gene expression, a 2.67-kb fragment of the rat sPLA(2)-IIA promoter was fused to a luciferase reporter construct and used to transfect mesangial cells. Hypoxia alone is not able to activate the sPLA(2) promoter, whereas it significantly enhances IL-1beta-stimulated promoter activity. A deletion mutant of the promoter that lacks the two putative hypoxia responsive elements (HRE) is devoid of the potentiating effect of hypoxia. Moreover, site-directed mutagenesis of either of the two HRE is sufficient to abolish the potentiating effect of hypoxia. Electrophoretic mobility shift assays show that HIF-2alpha, which is the only HIF subtype expressed in mesangial cells, binds to both HRE in the sPLA(2)-IIA promoter. In summary, the data show that in an inflammatory setting hypoxia is able to potentiate sPLA(2)-IIA expression and activity in renal mesangial cells, and thereby may critically contribute to enhanced formation of inflammatory lipid mediators seen in a diverse range of kidney diseases.
Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia--an active and well-tolerated regimen.
Authors: A D Ho, T Lipp, G Ehninger, H J Illiger, P Meyer, M Freund, W Hunstein
Journal: Journal of Clinical Oncology (1988)

Both mitoxantrone and etoposide have been shown to be active in monotherapy trials of relapsed and refractory acute myelogenous leukemia (AML). This phase II study was undertaken to assess the antitumor activity and toxicity of the combination in refractory and poor-risk AML. The regimen consisted of mitoxantrone, 10 mg/m2/d intravenously (IV), and etoposide, 100 mg/m2/d as short infusion, both on days 1 to 5. Sixty-one patients are evaluable for response and toxicity. Twenty-one were primarily refractory to conventional courses of cytarabine, daunorubicin, and thioguanine; 20 patients had poor-risk first relapse (relapse within 6 months of first complete remission [CR] or relapse under continuous maintenance therapy); 11 had second or subsequent relapses; and nine developed secondary AML after myelodysplastic phase or myelofibrosis. Twenty-six patients (42.6%) attained a CR and seven (11.5%) a partial remission (PR). The median duration of continuous CR was 4.7 months, with a range of 21 days to 14 months, excluding four patients who underwent autologous bone marrow transplantation. Severe myelosuppression was observed in all patients, with a median time to CR of 49 days. Nonhematologic toxicity included stomatitis (mainly grade 1 and 2) in 41 patients, nausea (mainly grade 1 and 2) in 44, infections (mainly grade 3) in 33, and fever of unidentified origin in 11. Other than transient, mild cardiac failure in nine patients, in some of them combined with grade 1 to 2 tachyarrhythmia, no other drug-related cardiac events were observed. Two cases of early death within the first 6 weeks of treatment were registered. Thus, the combination of mitoxantrone and etoposide is a highly active and well-tolerated regimen for refractory and poor-risk AML.
Venoocclusive disease of the liver after marrow transplantation: Histological correlates of clinical signs and symptoms
Authors: Howard M. Shulman, Lloyd B. Fisher, H. Gary Schoch, Kevin W. Henne, George B. McDonald
Journal: Hepatology (1994)

We evaluated the relationship between the signs and symptoms of the clinical syndrome called veno-occlusive disease of the liver after bone marrow transplantation and the histological findings in 76 patients who later came to autopsy. Coded necropsy liver was scored for individual histological features that were correlated with prospectively assessed clinical features that the patients had exhibited during life. Patients were stratified into two groups: those with severe clinical veno-occlusive disease (n = 32) and those without. Clinically severe veno-occlusive disease was statistically correlated with several zone 3 acinar changes: occluded hepatic venules, the frequency of occluded hepatic venules x degree of occlusion, eccentric luminal narrowing/phlebosclerosis, zone 3 sinusoidal fibrosis and zone 3 hepatocyte necrosis (all p < or = 0.03). There was a significant relationship between the number of these histological abnormalities in zone 3 of the liver acinus and a clinical diagnosis of severe veno-occlusive disease (p = 0.003). The presence of ascites was significantly correlated with occluded venules, zone 3 sinusoidal fibrosis and zone 3 hepatocyte necrosis (p = 0.001). Maximum serum bilirubin in the first 20 days after transplant was significantly correlated with sinusoidal fibrosis, hepatocyte necrosis and eccentric luminal sclerosis/phlebosclerosis (p < 0.01) but not with venular occlusion. The clinical syndrome of liver toxicity (commonly called veno-occlusive disease) that results from cytoreductive therapy before bone marrow transplant is strongly correlated with a constellation of histological lesions involving structures in zone 3 of the liver acinus and the hepatic venules into which sinusoidal blood flows. This study suggests that there is no single diagnostic histological feature. The severity of clinical veno-occlusive disease appears to be proportional to the number of such histological changes and is not due solely to occlusion of small hepatic venules.
Alterations in Cell Membrane Activity in Depression
Authors: J. MENDELS, A. FRAZER
Journal: American Journal of Psychiatry (1974)

Findings from a series of related experiments led to a working hypothesis suggesting that there may be an abnormality in aspects of cell membrane properties that normally regulate the movement of electrolytes across the plasma membrane in a subgroup of depressed patients. These patients appear to be responsive to lithium, and there is evidence that the postulated abnormality may be genetically determined. The authors outline the potential usefulness of the erythrocyte as a model for studying electrolyte transport in neurons.