tbuckley/cabot-search huggingface dataset:
Effects of Inter- α -inhibitor in Experimental Endotoxic Shock and Disseminated Intravascular Coagulation
Authors: MERCÉ JOURDAIN, ODILE CARRETTE, ANTOINE TOURNOYS, FRANÇOIS FOURRIER, CHARLOTTE MIZON, JACQUES MANGALABOYI, JENNY GOUDEMAND, JACQUES MIZON, CLAUDE CHOPIN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We investigated the effects of human inter- α -inhibitor (I α I) on hemodynamics, oxygenation, and coagulation parameters in a porcine model of endotoxic shock. Four groups of six animals were studied: (1) control, (2) I α I group receiving 30 mg/kg I α I over 30 min, (3) LPS group receiving 5 μ g · kg/min Escherichia coli endotoxin over 30 min, and (4) LPS + I α I group receiving 30 min after endotoxin 30 mg/kg/30 min I α I. We measured hemodynamic and oxygenation parameters, usual coagulation markers and plasma levels of thrombin-antithrombin complexes, antithrombin III activity, plasminogen activator tissue type, plasminogen activator inhibitor type 1, von Willebrand factor, tumor necrosis factor- α , and I α I at baseline and at 30, 60, 90, 120, 180, 240, and 300 min. In the I α I group, plasma I α I levels reached 447 ± 23 mg/L just after injection and 287 ± 39 mg/L at 300 min. I α I half-life was 7.3 ± 1.9 h. In the LPS + I α I group, I α I plasma levels decreased more rapidly, reaching 260 mg/L at 300 min. Compared with the LPS group, administration of I α I normalized the mean arterial pressure and cardiac index, improved the LPS-induced pulmonary hypertension, and resulted in the blunted increase in blood lactate and oxygen extraction ratio. A significant decrease in thrombin-antithrombin complexes and plasminogen activator inhibitor type 1 levels were observed. There was no significant difference in plasma tumor necrosis factor- α levels. We concluded that in this hypodynamic model of endotoxin shock, I α I administration resulted in a marked improvement in the hemodynamic, oxygenation, and coagulation parameters.
Gold Treatment in Rheumatoid Arthritis
Authors: T. N. Fraser
Journal: Annals of the Rheumatic Diseases (1945)

<h3>Abstract</h3> NFL players have a traumatic injury rate approaching 100%; chronic pain with decreased concentration occur commonly. This study examined the role of a novel focused muscle contraction therapy for the treatment of chronic pain and identified its impact on brain activity. Chronic pain was assessed by numerical score, neuropathic component, and impact on daily activities in 8 retired players. Brain activity was characterized by QEEG with low-resolution electromagnetic tomography analysis and functional measures of visual and auditory attention. Focused muscle contraction muscle therapy administered twice weekly for 6 months was tapered to twice monthly by 12 months. Brodmann Areas (BA) 4 and 9, known to associate with chronic pain, showed values outside the clinically normal range; mean pain duration was 16.5 ± 12.9 years. At 6 months, 5/8 subjects reported pain scores of 0. High beta wave activity was seen in BA 19, 21, 29, 30, and 39, affecting auditory, visual, and body perceptions. Clinically relevant improvements were observed in auditory attention and visual stamina. Pain relief was sustained through 18 months of follow-up. Focused muscle contraction therapy appears to redirect brain activity to new areas of activity which are associated with long-lasting relief of chronic pain and its detriments. This study was registered with clinicaltrial.gov #NCT04822311.
Route of Immunization with Peptide-pulsed Dendritic Cells Controls the Distribution of Memory and Effector T Cells in Lymphoid Tissues and Determines the Pattern of Regional Tumor Control
Authors: David W. Mullins, Stacey L. Sheasley, Rebecca M. Ream, Timothy N.J. Bullock, Yang-Xin Fu, Victor H. Engelhard
Journal: The Journal of Experimental Medicine (2003)

We have established that the route of immunization with peptide-pulsed, activated DC leads to memory CD8+ T cells with distinct distributions in lymphoid tissues, which determines the ability to control tumors growing in different body sites. Both intravenous (i.v.) and subcutaneous (s.c.) immunization induced memory T cells in spleen and control of metastatic-like lung tumors. s.c. immunization also induced memory T cells in lymph nodes (LNs), imparting protection against subcutaneously growing tumors. In contrast, i.v. immunization-induced memory was restricted to spleen and failed to impart protective immunity against subcutaneously growing tumors. Memory cell distribution and tumor control were both linked to injection route–dependent localization of DCs in lymphoid compartments. Using peripheral LN–ablated mice, these LNs were shown to be essential for control of subcutaneously growing tumors but not lung metastases; in contrast, using immunized asplenic mice, we found that the spleen is necessary and sufficient for control of lung tumors, but unnecessary for control of subcutaneously growing tumors. These data demonstrate the existence of a previously undescribed population of splenic-resident memory CD8 T cells that are essential for the control of lung metastases. Thus, regional immunity based on memory T cell residence patterns is an important factor in DC-based tumor immunotherapy.
Phase I Study of Hepatic Arterial Melphalan Infusion and Hepatic Venous Hemofiltration Using Percutaneously Placed Catheters in Patients With Unresectable Hepatic Malignancies
Authors: James F. Pingpank, Steven K. Libutti, Richard Chang, Bradford J. Wood, Ziv Neeman, Anthony W. Kam, William D. Figg, Souping Zhai, Tatiana Beresneva, Geoffrey D. Seidel, H. Richard Alexander
Journal: Journal of Clinical Oncology (2005)

Purpose We conducted a phase I study of a 30-minute hepatic artery infusion of melphalan via a percutaneously placed catheter and hepatic venous hemofiltration using a double balloon catheter positioned in the retrohepatic inferior vena cava to shunt hepatic venous effluent through an activated charcoal filter and then to the systemic circulation. The purpose of the study was to demonstrate feasibility in an initial cohort and subsequently determine the maximum tolerated dose and dose-limiting toxicity of melphalan. Patients and Methods The initial cohort (n = 12) was treated with 2.0 mg/kg of melphalan before dose escalation to 3.5 mg/kg (n = 16). Total hepatic drug delivery, systemic levels, and percent filter efficiency were determined. Patients were assessed for hepatic and systemic toxicity and response. Results A total of 74 treatments were administered to 28 patients. Twelve patients with primary and metastatic hepatic tumors received 30 treatments (mean, 2.5 per patient) at an initial melphalan dose of 2.0 mg/kg. At 3.5 mg/kg, a dose-limiting toxicity (neutropenia and/or thrombocytopenia) was observed in two of six patients. Transient grade 3/4 hepatic and systemic toxicity was seen after 19% and 66% of treatments, respectively. An overall radiographic response rate of 30% was observed in treated patients. In the 10 patients with ocular melanoma, a 50% overall response rate was observed, including two complete responses. Conclusion Delivery of melphalan via this system is feasible, with limited, manageable toxicity and evidence of substantial antitumor activity; 3 mg/kg is the maximum safe tolerated dose of melphalan administered via this technique.
Empirical Diagnosis of Pneumocystis carinii Pneumonia-Reply
Authors: Richard E. Chaisson
Journal: JAMA (1988)

<h3>In Reply.</h3> —Drs Moskowitz and Arsura raise several important points concerning the diagnosis and management of<i>Pneumocystis</i>pneumonia to which we would like to respond. First, while silver-methenamine and Giemsa staining of bronchoalveolar lavage specimens are highly sensitive for diagnosing PCP, in published series the yield is only about 90% to 95%.<sup>1</sup>We have recently noted, however, that the sensitivity of bronchoalveolar lavage testing is increasing, perhaps reflecting the greater experience of our laboratory staff. In our institution, patients suspected to have PCP with negative bronchoalveolar lavage specimens undergo repeated bronchoscopy with transbronchial biopsy, a procedure that increases the diagnostic yield to 100%.<sup>1</sup>Second, response to antimicrobial therapy in patients with PCP is usually gradual, with defervescence and a reduction in dyspnea occurring on average after five to seven days of therapy.<sup>2,3</sup> A rapid response to sulfamethoxazole and trimethoprim in a patient with negative bronchoalveolar lavage stains,
PATHOGENIC FACTORS IN VASCULAR LESIONS OF EXPERIMENTAL SERUM SICKNESS
Authors: William T. Kniker, Charles G. Cochrane
Journal: The Journal of Experimental Medicine (1965)

The present studies suggest that polymorphonuclear leukocytes (PMN's) are essential for the development of cardiovascular lesions in serum sickness. In the absence of PMN's, necrotic vascular lesions were never seen and endothelial proliferation in arteries was inhibited. Zones of fibrinoid deposits did not occur. By contrast, at least two-thirds of the control animals exhibited endothelial proliferation, and half had necrosis of arterial walls, usually with fibrinoid deposits. In arterial lesions that involved the intima and media, the internal elastic lamina was disrupted. This was associated with accumulations of PMN's and was prevented when PMN's were depleted. The observations suggested that the elastic lamina acts as a barrier to the outward spread of inflammation in arteries and that it is an important substrate of PMN action. Although glomerulitis and proteinuria developed in PMN-depleted animals, no conclusions could be drawn concerning the pathogenic role of PMN's in renal lesions, since PMN depletion could not be effected before the onset of immune elimination without influencing the immune response itself. Host complement (ß1C-globulin) was localized along with the antigen and rabbit gamma globulin in glomeruli and arteries showing lesions. In the glomeruli these deposits formed a granular lining along the area of the basement membrane. In arteries the fluorescent amorphous particles were in the intima and media of inflamed vessels. The immune response to BSA and the incidence and severity of cardiovascular and renal lesions were enhanced by the intravenous administration of pooled rabbit antiserum to BSA given 18 hours before BSA antigen and by injecting endotoxin along with the BSA. These additions to the usual procedure of inducing serum sickness did not appear to change the quality of the disease. In normal rabbits, the peak incidence of cardiovascular lesions was early in immune elimination of antigen, at a time when levels of circulating complexes was maximal. Conversely, the severest renal injury was noted several days later, at the completion of immune elimination.
Maternal anti-platelet β3 integrins impair angiogenesis and cause intracranial hemorrhage
Authors: Issaka Yougbaré, Sean Lang, Hong Yang, Pingguo Chen, Xu Zhao, Wei-She Tai, Darko Zdravic, Brian Vadasz, Conglei Li, Siavash Piran, Alexandra Marshall, Guangheng Zhu, Heidi Tiller, Mette Kjaer Killie, Shelley Boyd, Howard Leong-Poi, Xiao-Yan Wen, Bjorn Skogen, S. Lee Adamson, John Freedman, Heyu Ni
Journal: Journal of Clinical Investigation (2015)

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening disease in which intracranial hemorrhage (ICH) is the major risk. Although thrombocytopenia, which is caused by maternal antibodies against β3 integrin and occasionally by maternal antibodies against other platelet antigens, such as glycoprotein GPIbα, has long been assumed to be the cause of bleeding, the mechanism of ICH has not been adequately explored. Utilizing murine models of FNAIT and a high-frequency ultrasound imaging system, we found that ICH only occurred in fetuses and neonates with anti-β3 integrin-mediated, but not anti-GPIbα-mediated, FNAIT, despite similar thrombocytopenia in both groups. Only anti-β3 integrin-mediated FNAIT reduced brain and retina vessel density, impaired angiogenic signaling, and increased endothelial cell apoptosis, all of which were abrogated by maternal administration of intravenous immunoglobulin (IVIG). ICH and impairment of retinal angiogenesis were further reproduced in neonates by injection of anti-β3 integrin, but not anti-GPIbα antisera. Utilizing cultured human endothelial cells, we found that cell proliferation, network formation, and AKT phosphorylation were inhibited only by murine anti-β3 integrin antisera and human anti-HPA-1a IgG purified from mothers with FNAIT children. Our data suggest that fetal hemostasis is distinct and that impairment of angiogenesis rather than thrombocytopenia likely causes FNAIT-associated ICH. Additionally, our results indicate that maternal IVIG therapy can effectively prevent this devastating disorder.
Effect of leukotriene receptor antagonist therapy on the risk of asthma exacerbations in patients with mild to moderate asthma: an integrated analysis of zafirlukast trials
Authors: N. C Barnes
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Asthma exacerbations contribute substantially to morbidity, and their reduction is an important therapeutic objective. In this integrated analysis the risk of asthma exacerbations was assessed during treatment with the leukotriene receptor antagonist zafirlukast. <h3>METHODS</h3> Data were collected from all five double blind, multicentre, randomised, placebo controlled, 13 week trials of zafirlukast 20 mg twice daily performed in steroid-naive patients with mild to moderate asthma. Exacerbation data were collected prospectively during monitoring of adverse events and concomitant medication use. Pooled data were used to assess the relative risk of asthma exacerbations using three definitions: worsening of asthma leading to withdrawal from the study; requirement for additional anti-asthma therapy (excluding increased short acting β<sub>2</sub> agonist use); and requirement for oral corticosteroid therapy. <h3>RESULTS</h3> The proportion of patients with an asthma exacerbation leading to withdrawal was consistently lower in the group treated with zafirlukast 20 mg twice daily than in the placebo group. Overall, the risk of an asthma exacerbation requiring withdrawal from zafirlukast therapy was approximately half that of placebo (odds ratio 0.45; 95% CI 0.26 to 0.76; p = 0.003). Similar results were observed for exacerbations requiring additional control medication (odds ratio = 0.47; 95% CI 0.30 to 0.74; p = 0.001) and oral corticosteroid rescue (odds ratio = 0.53; 95% CI 0.32 to 0.86; p = 0.010). <h3>CONCLUSIONS</h3> Zafirlukast in a dose of 20 mg twice daily reduces the risk of asthma exacerbations and the need for additional anti-asthma therapies, fulfilling an important goal of control medication in patients with mild to moderate asthma.
Prefrontal Lobotomy: Stepping-Stone or Pitfall?
Authors: J. M.C. HOLDEN, T. M. ITIL, L. HOFSTATTER
Journal: American Journal of Psychiatry (1970)

The standard prefrontal lobotomy operation was introduced as a treatment for mental illness in 1935. Although many patients benefited from it, the neurological and psychiatric side effects often proved more disabling than the psychiatric illness itself. However, the introduction of the operation encouraged scientists to investigate the functions of the various areas of man's frontal lobes in greater detail and stimulated other workers to develop modified operative procedures. The authors discuss some of the advances made in both these areas in recent years and emphasize the continuing importance of the inferomedial lobotomy operation in psychiatric treatment.
Oblimersen combined with docetaxel, adriamycin and cyclophosphamide as neo-adjuvant systemic treatment in primary breast cancer: final results of a multicentric phase I study
Authors: J. Rom, G. von Minckwitz, W. Eiermann, M. Sievert, B. Schlehe, F. Marmé, F. Schuetz, A. Scharf, M. Eichbaum, H.-P. Sinn, M. Kaufmann, C. Sohn, A. Schneeweiss
Journal: Annals of Oncology (2008)
Antitumor Effect of Antibody against a SEREX-Defined Antigen (UOEH-LC-1) on Lung Cancer Xenotransplanted into Severe Combined Immunodeficiency Mice
Authors: Makiko Mizukami, Takeshi Hanagiri, Manabu Yasuda, Koji Kuroda, Yoshiki Shigematsu, Tetsuro Baba, Takashi Fukuyama, Yoshika Nagata, Tetsuya So, Yoshinobu Ichiki, Masakazu Sugaya, Tomoko So, Mitsuhiro Takenoyama, Kenji Sugio, Kosei Yasumoto
Journal: Cancer Research (2007)

Abstract We previously reported the humoral immune response of tumor-infiltrating B lymphocytes in a lung cancer patient and 22 genes coding tumor-associated antigens identified using the serological identification of antigens by recombinant expression cloning method. In this study, we investigated one of these genes, designated University of Occupational and Environmental Health—Lung cancer antigen-1 (UOEH-LC-1), which has an extracellular domain. Quantitative reverse transcription-PCR revealed that UOEH-LC-1 was expressed ubiquitously in the normal tissues tested. However, it was overexpressed in 5 of 11 (45.5%) lung cancer cell lines and also in 9 of 15 (60%) lung cancer tissues compared with the paired normal lung tissues. A sequence analysis revealed that UOEH-LC-1 has a transmembrane domain. Flow cytometry analysis using a polyclonal antibody against UOEH-LC-1 revealed positive staining on lung cancer cell lines that were positive for expression of mRNA of UOEH-LC-1. Phage plaque assay showed the specific reactivity of anti–UOEH-LC-1 antibody against UOEH-LC-1 protein derived from the antigen encoding phage. By immunohistochemical staining with the anti–UOEH-LC-1 antibody, 7 of 28 (25.0%) lung cancer specimens showed positive staining on the cell surface. The administration of anti–UOEH-LC-1 antibody inhibited the growth of the UOEH-LC-1–positive tumors that were xenotransplanted into severe combined immunodeficiency mice. Complement-dependent cytotoxicity was one of the mechanisms to suppress the tumor growth. These results suggest that the antibody against UOEH-LC-1 therefore seems to have a promising therapeutic potential as a treatment for lung cancer. [Cancer Res 2007;67(17):8351–7]
Renin secretion in the chronically perfused pulseless calf. Evidence for failure of stimulation by decreased pulse pressure.
Authors: P M Shoor, U M Marzec, L D Griffith, F S Hammill, R B Dilley, E F Bernstein
Journal: Circulation Research (1979)

To study the influence of arterial pulse pressure on renin release, a chronic pulseless calf preparation was developed using a centrifugal left ventricular bypass blood pump. After pump implantation and recovery, control measurements of renal vein and arterial plasma renin activity, arterial pressure, and renal artery flow were obtained. The centrifugal bypass pump rate then was increased to capture cardiac output completely, and nine conscious calves were perfused in a nonpulsatile manner (pulse pressure less than 5-10 mm Hg) for 48 hours. Nonpulsatile perfusion was well tolerated and serum sodium, potassium, creatinine, and blood urea nitrogen were unchanged during bypass. Mean arterial pressure remained relatively constant [114 +/- 3 (SE) mm Hg] during bypass, and was not significantly changed from control. Although renal blood flow decreased slightly from control (667 +/- 84 ml/min) during the nonpulsatile perfusion period (555 +/- 73 ml/min), renin secretion did not increase significantly from control (482 +/- 81 ng angiotensin I/ml per hr per min) during the bypass period (531 +/- 99). A diurnal cycle of renin secretin was observed during the pulseless perfusions. These data document the lack of any significant stimulatory influence of decreased pulse pressure on renin secretion in a chronic awake calf model.
The transcription factor IFN regulatory factor–4 controls experimental colitis in mice via T cell–derived IL-6
Authors: Jonas Mudter, Lioubov Amoussina, Mirjam Schenk, Jingling Yu, Anne Brüstle, Benno Weigmann, Raja Atreya, Stefan Wirtz, Christoph Becker, Arthur Hoffman, Imke Atreya, Stefan Biesterfeld, Peter R. Galle, Hans A. Lehr, Stefan Rose-John, Christoph Mueller, Michael Lohoff, Markus F. Neurath
Journal: Journal of Clinical Investigation (2008)

The proinflammatory cytokine IL-6 seems to have an important role in the intestinal inflammation that characterizes inflammatory bowel diseases (IBDs) such as Crohn disease and ulcerative colitis. However, little is known about the molecular mechanisms regulating IL-6 production in IBD. Here, we assessed the role of the transcriptional regulator IFN regulatory factor–4 (IRF4) in this process. Patients with either Crohn disease or ulcerative colitis exhibited increased IRF4 expression in lamina propria CD3+ T cells as compared with control patients. Consistent with IRF4 having a regulatory function in T cells, in a mouse model of IBD whereby colitis is induced in RAG-deficient mice by transplantation with CD4+CD45RBhi T cells, adoptive transfer of wild-type but not IRF4-deficient T cells resulted in severe colitis. Furthermore, IRF4-deficient mice were protected from T cell–dependent chronic intestinal inflammation in trinitrobenzene sulfonic acid– and oxazolone-induced colitis. In addition, IRF4-deficient mice with induced colitis had reduced mucosal IL-6 production, and IRF4 was required for IL-6 production by mucosal CD90+ T cells, which it protected from apoptosis. Finally, the protective effect of IRF4 deficiency could be abrogated by systemic administration of either recombinant IL-6 or a combination of soluble IL-6 receptor (sIL-6R) plus IL-6 (hyper–IL-6). Taken together, our data identify IRF4 as a key regulator of mucosal IL-6 production in T cell–dependent experimental colitis and suggest that IRF4 might provide a therapeutic target for IBDs.
High frequency of normal DJH joints in B cell progenitors in severe combined immunodeficiency mice.
Authors: J L Pennycook, Y Chang, J Celler, R A Phillips, G E Wu
Journal: The Journal of Experimental Medicine (1993)

The severe combined immunodeficiency (scid) mouse has a defective V(D)J recombinase activity that results in arrested lymphoid development at the pro-B cell stage in the B lineage. The defect is not absolute and scid mice do attempt gene rearrangement. Indeed, approximately 15% of all scid mice develop detectable levels of oligoclonal serum immunoglobulin and T cell activity. To gain more insight into the scid defect and its effect on V(D)J rearrangement, we analyzed DJH recombination in scid bone marrow. We determined that DJH structures are present in scid bone marrow and occur at a frequency only 10-100 times less than C.B-17+/+. The scid DJH repertoire is limited and resembles fetal liver DJH junctions, with few N insertions and predominant usage of reading frame 1. Moreover, 70% of the DJH structures were potentially productive, indicating that normal V(D)J recombinants should be arising continually.