tbuckley/cabot-search huggingface dataset:
RS3PE syndrome presenting as vascular endothelial growth factor associated disorder
Authors: K Arima, T Origuchi, M Tamai, N Iwanaga, Y Izumi, M Huang, F Tanaka, M Kamachi, K Aratake, H Nakamura, H Ida, M Uetani, A Kawakami, K Eguchi
Journal: Annals of the Rheumatic Diseases (2005)

<h3>Abstract</h3> <h3>Background</h3> The COVID-19 pandemic has caused interruptions to chronic disease and non-emergency treatment. The purpose of this study is to examine which socioeconomic status groups are most at risk of treatment interruption. <h3>Methods</h3> This cross-sectional internet monitor study was conducted on December 22–26, 2020, when Japan experienced its third wave of COVID-19 infection. Out of a total of 33,302 participants in the survey, 9510 (5392 males and 4118 females) who responded that they required regular treatment or hospital visits were included in the analysis. A multilevel logistic model nested in the prefecture of residence was used to estimate the odds ratio (OR) for treatment disruption. We examined separate multivariate models for socioeconomic factors, health factors, and lifestyle factors. <h3>Results</h3> During a period of rapid COVID-19 infection, about 11% of Japanese workers who required regular treatment experienced interruptions to their treatment. The OR of treatment interruption associated with not being married compared to being married was 1.44; manual labor work compared to desk work was 1.30; loss of employment when the COVID-19 pandemic started and continued unemployment compared to being employed over the entire pandemic period was 1.62 and 2.57, respectively; and feeling financially unstable was 2.92. <h3>Conclusion</h3> Treatment interruption is a new health inequality brought about by COVID-19 with possible medium- and long-term effects, including excess mortality, morbidity, and productivity loss due to increased presenteeism. Efforts are needed to reduce treatment interruptions among workers who require regular treatment.
Phase III Study of Adjuvant Vaccination With Bec2/Bacille Calmette-Guerin in Responding Patients With Limited-Disease Small-Cell Lung Cancer (European Organisation for Research and Treatment of Cancer 08971-08971B; Silva Study)
Authors: Giuseppe Giaccone, Channa Debruyne, Enriqueta Felip, Paul B. Chapman, Stefan C. Grant, Michael Millward, Luc Thiberville, Giannicola D'addario, Corneel Coens, Lisa S. Rome, Petr Zatloukal, Oriol Masso, Catherine Legrand
Journal: Journal of Clinical Oncology (2005)

Bec2 is an anti-idiotypic antibody that mimics GD3, a ganglioside that is expressed on the surface of tumor cells and is of neuroectodermal origin. We assessed whether Bec2/bacille Calmette-Guerin (BCG) vaccination prolongs survival in patients with limited-disease small-cell lung cancer (SCLC) after a major response to chemotherapy and chest radiation.Patients were randomly assigned to receive five vaccinations of Bec2 (2.5 mg)/BCG vaccine or follow-up. Vaccination was given over a 10-week period. The sample size was targeted to detect an increase in median survival of 40% after random assignment, and stratification was by performance status, response, and institution. Quality of life was assessed by using the European Organisation for Research and Treatment of Cancer instrument. Humoral response was assessed in patients who received vaccination.A total of 515 patients were randomly assigned. The primary toxicities of vaccination were transient skin ulcerations and mild flu-like symptoms. There was no improvement in survival, progression-free survival, or quality of life in the vaccination arm. Median survival from randomization was 16.4 and 14.3 months in the observation and vaccination arms (P = .28), respectively. Among vaccinated patients, a trend toward prolonged survival was observed in those (one third) who developed a humoral response (P = .085). Multivariate analysis showed a positive impact on survival by prior treatment with concomitant chemoradiotherapy, prophylactic cranial irradiation, female sex, low lactate dehydrogenase, and normal platelets.Vaccination with Bec2/BCG has no impact on outcome of patients with limited-disease SCLC responding to combined-modality treatment. Vaccination strategies in SCLC may still be warranted using vaccines that produce a better immunologic response.
Adenosine A2B Receptors
Authors: Igor Feoktistov, Italo Biaggioni
Journal: Pharmacological Reviews (1997)

Adenosine is an endogenous nucleoside that modulates many physiological processes. Its actions are mediated by interaction with specific cell membrane receptors. Four subtypes of adenosine receptors have been cloned: A1, A2A, A2B, and A3. Significant advancement has been made in the understanding of
Immunization with neuronal nicotinic acetylcholine receptor induces neurological autoimmune disease
Authors: Vanda A. Lennon, Leonid G. Ermilov, Joseph H. Szurszewski, Steven Vernino
Journal: Journal of Clinical Investigation (2003)

Neuronal nicotinic AChRs (nAChRs) are implicated in the pathogenesis of diverse neurological disorders and in the regulation of small-cell lung carcinoma growth. Twelve subunits have been identified in vertebrates, and mutations of one are recognized in a rare form of human epilepsy. Mice with genetically manipulated neuronal nAChR subunits exhibit behavioral or autonomic phenotypes. Here, we report the first model of an acquired neuronal nAChR disorder and evidence for its pertinence to paraneoplastic neurological autoimmunity. Rabbits immunized once with recombinant α3 subunit (residues 1–205) develop profound gastrointestinal hypomotility, dilated pupils with impaired light response, and grossly distended bladders. As in patients with idiopathic and paraneoplastic autoimmune autonomic neuropathy, the severity parallels serum levels of ganglionic nAChR autoantibody. Failure of neurotransmission through abdominal sympathetic ganglia, with retention of neuronal viability, confirms that the disorder is a postsynaptic channelopathy. In addition, we found ganglionic nAChR protein in small-cell carcinoma lines, identifying this cancer as a potential initiator of ganglionic nAChR autoimmunity. The data support our hypothesis that immune responses driven by distinct neuronal nAChR subtypes expressed in small-cell carcinomas account for several lung cancer–related paraneoplastic disorders affecting cholinergic systems, including autoimmune autonomic neuropathy, seizures, dementia, and movement disorders.
Reversed halo sign in pulmonary zygomycosis
Authors: Myrna C B Godoy, Edith M Marom
Journal: Thorax (2011)

We read with interest the article ‘The atoll sign’ by Walsh and Roberton1 in the November issue of Thorax . The authors report a case of cryptogenic organising pneumonia with the atoll sign, also called the reversed halo sign. As mentioned by the authors, this CT sign was first described in cryptogenic organising pneumonia and was initially considered to be specific for this disease.2 It was subsequently reported in …
Alloreactivity in Renal Transplant Recipients with and without Chronic Allograft Nephropathy
Authors: Emilio D. Poggio, Michael Clemente, Jocelyn Riley, Meagan Roddy, Neil S. Greenspan, Cora Dejelo, Nader Najafian, Mohamed H. Sayegh, Donald E. Hricik, Peter S. Heeger
Journal: Journal of the American Society of Nephrology (2004)

The pathogenesis of chronic allograft nephropathy (CAN) involves both immunologic (antigen-dependent) and nonimmunologic (antigen-independent) mechanisms. In order to provide further insight into the immunologic basis of this disease, a cross-sectional analysis of cellular and humoral immunity in human renal allograft recipients with or without deteriorating renal function and biopsy proven CAN was performed. Interferon-γ enzyme-linked immunosorbent spot assays were used to assess cellular immunity to donor, or fully mismatched third-party stimulator cells (direct pathway), and to synthetic peptides derived from donor HLA molecules (indirect pathway). Anti-HLA antibodies were evaluated by flow cytometry using HLA-coated beads. Both the mean frequencies of donor-reactive peripheral blood lymphocytes and the number of individuals who responded to donor antigens per group were statistically higher in CAN patients versus control subjects ( P < 0.02). Calculated ratios of donor/third-party enzyme-linked immunosorbent spot responses showed mean values of 2.61 ± 3.0 in the CAN group, with ratios of 0.50 to 0.72 ± 0.42 in control subjects ( P < 0.001), confirming that direct, donor-specific cellular immunity predominated in patients with CAN. Fifty percent of CAN patients studied exhibited donor peptide reactivity compared with only 28.6% in control subjects. Finally, 33% of patients in the CAN group developed new posttransplantation anti-HLA antibodies compared with only 4% in the control group ( P < 0.05). Overall, the results suggest that persistent cell-mediated and humoral alloimmunity contribute to the development of CAN and further demonstrate that anti-donor immunity in patients with CAN is heterogeneous. Immune monitoring to predict long-term outcome should include multiple measures of cellular and humoral immunity.
Transactivation of Sphingosine-1–Phosphate Receptors by FcεRI Triggering Is Required for Normal Mast Cell Degranulation and Chemotaxis
Authors: Puneet S. Jolly, Meryem Bektas, Ana Olivera, Claudia Gonzalez-Espinosa, Richard L. Proia, Juan Rivera, Sheldon Milstien, Sarah Spiegel
Journal: The Journal of Experimental Medicine (2004)

Mast cells secrete various substances that initiate and perpetuate allergic responses. Cross-linking of the high-affinity receptor for IgE (FcεRI) in RBL-2H3 and bone marrow–derived mast cells activates sphingosine kinase (SphK), which leads to generation and secretion of the potent sphingolipid mediator, sphingosine-1–phosphate (S1P). In turn, S1P activates its receptors S1P1 and S1P2 that are present in mast cells. Moreover, inhibition of SphK blocks FcεRI-mediated internalization of these receptors and markedly reduces degranulation and chemotaxis. Although transactivation of S1P1 and Gi signaling are important for cytoskeletal rearrangements and migration of mast cells toward antigen, they are dispensable for FcεRI-triggered degranulation. However, S1P2, whose expression is up-regulated by FcεRI cross-linking, was required for degranulation and inhibited migration toward antigen. Together, our results suggest that activation of SphKs and consequently S1PRs by FcεRI triggering plays a crucial role in mast cell functions and might be involved in the movement of mast cells to sites of inflammation.
The NHLBI Lymphangioleiomyomatosis Registry
Authors: Jay H. Ryu, Joel Moss, Gerald J. Beck, Jar-Chi Lee, Kevin K. Brown, Jeffrey T. Chapman, Geraldine A. Finlay, Eric J. Olson, Stephen J. Ruoss, Janet R. Maurer, Thomas A. Raffin, Hannah H. Peavy, Kevin McCarthy, Angelo Taveira-DaSilva, Francis X. McCormack, Nilo A. Avila, Rosamma M. DeCastro, Susan S. Jacobs, Mario Stylianou, Barry L. Fanburg
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Pulmonary lymphangioleiomyomatosis is a progressive cystic lung disease that is associated with infiltration of atypical smooth muscle-like cells. Previous descriptions of clinical characteristics of subjects with lymphangioleiomyomatosis have been based on a limited number of patients.To describe the clinical characteristics of subjects with pulmonary lymphangioleiomyomatosis, both sporadic and tuberous sclerosis-related forms.Over a 3-yr period, from 1998 to 2001, 243 subjects with pulmonary lymphangioleiomyomatosis were enrolled into a national registry; 13 subjects who had already undergone lung transplantation were excluded for the purposes of this report.All 230 subjects were women, aged 18 to 76 yr (mean +/- SE, 44.5 +/- 0.65 yr). The average age at onset of symptoms was 38.9 +/- 0.73 yr and at diagnosis was 41.0 +/- 0.65 yr. Tuberous sclerosis complex was present in 14.8% of subjects. Pulmonary manifestations, most commonly spontaneous pneumothorax, were the primary events leading to the diagnosis in 86.5% of cases. Nearly 55% of the subjects were being treated with a progesterone derivative. An obstructive pattern on pulmonary function testing was observed in 57.3% of the subjects, whereas 33.9% had normal spirometric results. Women with tuberous sclerosis-related lymphangioleiomyomatosis were younger and had less impaired lung function compared with those with the sporadic form.The age range of women afflicted with pulmonary lymphangioleiomyomatosis is broader than previously appreciated and the degree of pulmonary function can be quite variable, with one-third of subjects having normal spirometry at enrollment into this registry.
TLR4 Signaling Mediates Inflammation and Tissue Injury in Nephrotoxicity
Authors: Binzhi Zhang, Ganesan Ramesh, Satoshi Uematsu, Shizuo Akira, W. Brian Reeves
Journal: Journal of the American Society of Nephrology (2008)

The molecular mechanisms of acute kidney injury (AKI) remain unclear. Toll-like receptors (TLRs), widely expressed on leukocytes and kidney epithelial cells, regulate innate and adaptive immune responses. The present study examined the role of TLR signaling in cisplatin-induced AKI. Cisplatin-treated wild-type mice had significantly more renal dysfunction, histologic damage, and leukocytes infiltrating the kidney than similarly treated mice with a targeted deletion of TLR4 [Tlr4(-/-)]. Levels of cytokines in serum, kidney, and urine were increased significantly in cisplatin-treated wild-type mice compared with saline-treated wild-type mice and cisplatin-treated Tlr4(-/-) mice. Activation of JNK and p38, which was associated with cisplatin-induced renal injury in wild-type mice, was significantly blunted in Tlr4(-/-) mice. Using bone marrow chimeric mice, it was determined that renal parenchymal TLR4, rather than myeloid TLR4, mediated the nephrotoxic effects of cisplatin. Therefore, activation of TLR4 on renal parenchymal cells may activate p38 MAPK pathways, leading to increased production of inflammatory cytokines, such as TNF-alpha and subsequent kidney injury. Targeting the TLR4 signaling pathways may be a feasible therapeutic strategy to prevent cisplatin-induced AKI in humans.
24-hour leg and forearm haemodynamics in transected spinal cord subjects
Authors: E Casiglia
Journal: Cardiovascular Research (1999)

Objective: A circadian rhythm of blood pressure has been demonstrated both in subjects who are physically active during the day and in those confined to bed. The study of the circadian rhythm of arterial flow and peripheral resistance, on the other hand, is limited to pioneer experiments. This paper is aimed at demonstrating that leg peripheral resistance has circadian fluctuations which are modulated by spinal neural traffic. Methods: Eleven normal (able-bodied) human subjects and 11 patients with spinal transection due to spinal cord injury (SCI) were studied. They were confined to bed for 24 h. Blood pressure and heart rate were monitored every 15 min with an automatic device and leg flow with an automatic strain–gauge plethysmograph synchronised to the pressurometer. Peripheral resistance was calculated at the same intervals. Results: In able-bodied subjects leg resistance was significantly higher during waking hours (when the sympathetic system is more activated) than during sleep, while in subjects with spinal cord injury no difference was detected between day-time and night-time. Conclusions: The circadian rhythm is controlled by adrenergic fibres transmitted via the spinal cord.
Surrogate Decision Making in the Internet Age
Authors: Jessica Berg
Journal: The American Journal of Bioethics (2012)

The computer revolution has had an enormous effect on all aspects of the practice of medicine, yet little thought has been given to the role of social media in identifying treatment choices for incompetent patients. We are currently living in the "Internet age" and many people have integrated social media into all aspects of their lives. As use becomes more prevalent, and as users age, social media are more likely to be viewed as a source of information regarding medical care preferences. This article explores the ethical and legal issues raised by the use of social media in surrogate decision making.
<i>In vivo</i> Target Modulation and Biological Activity of CHIR-258, a Multitargeted Growth Factor Receptor Kinase Inhibitor, in Colon Cancer Models
Authors: Sang Hoon Lee, Daniel Lopes de Menezes, Jayesh Vora, Alex Harris, Helen Ye, Lara Nordahl, Evelyn Garrett, Emil Samara, Sharon Lea Aukerman, Arnold B. Gelb, Carla Heise
Journal: Clinical Cancer Research (2005)

To evaluate the therapeutic and biological effects of CHIR-258, an orally bioavailable, potent inhibitor of class III-V receptor tyrosine kinases, in colon cancer models.The pharmacologic activity of CHIR-258 was characterized by monitoring target modulation as well as by evaluating the antitumor and antiangiogenic effects in human colon xenograft models.CHIR-258 inhibits vascular endothelial growth factor receptor 1/2, fibroblast growth factor receptor 1/3, and platelet-derived growth factor receptor beta (PDGFRbeta) and shows both antitumor and antiangiogenic activities in vivo. Treatment of KM12L4a human colon cancer cells with CHIR-258 resulted in a dose-dependent inhibition of vascular endothelial growth factor receptor 1 and PDGFRbeta phosphorylation and reduction of phosphorylated extracellular signal-regulated kinase (ERK) levels, indicating modulation of target receptors and downstream signaling. In vivo administration of CHIR-258 resulted in significant tumor growth inhibition and tumor regressions, including large, established tumors (500-1,000 mm(3)). Immunohistochemical analysis showed a reduction of phosphorylated PDGFRbeta and phosphorylated ERK in tumor cells after oral dosing with CHIR-258 compared with control tumors. These changes were accompanied by decreased tumor cell proliferation rate and reduced intratumoral microvessel density. CHIR-258 inhibited the phosphorylation of PDGFRbeta and ERK phosphorylation in tumors within 2 hours following dosing and the inhibitory activity was sustained for >24 hours. Significant antitumor activity was observed with intermittent dosing schedules, indicating a sustained biological activity.These studies provide evidence that biological activity of CHIR-258 in tumors correlates with efficacy and aids in the identification of potential biomarkers of this multitargeted receptor tyrosine kinase inhibitor. CHIR-258 exhibits properties that make it a promising candidate for clinical development in a variety of solid and hematologic malignancies.
An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis
Authors: L Skoldstam
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To investigate the efficacy of a Mediterranean diet (MD) versus an ordinary Western diet for suppression of disease activity in patients with rheumatoid arthritis (RA). <b>Methods:</b> Patients with well controlled, although active RA of at least two years' duration, who were receiving stable pharmacological treatment, were invited to participate. All patients were randomly allocated to the MD or the control diet (CD). To achieve good compliance with prescribed diets all patients were for the first three weeks served the MD or the CD, respectively, for lunch and dinner at the outpatient clinic's canteen. Clinical examinations were performed at baseline, and again in the 3rd, 6th, and 12th week. A composite disease activity index (DAS28), a physical function index (Health Assessment Questionnaire (HAQ)), a health survey of quality of life (Short Form-36 (SF-36)), and the daily consumption of non-steroidal anti-inflammatory drugs were used as primary efficacy variables. <b>Results:</b> From baseline to the end of the study the patients in the MD group (n=26) showed a decrease in DAS28 of 0.56 (p&lt;0.001), in HAQ of 0.15 (p=0.020), and in two dimensions of the SF-36 Health Survey: an increase in "vitality" of 11.3 (p=0.018) and a decrease in "compared with one year earlier" of 0.6 (p=0.016). For the control patients (n=25) no significant change was seen at the end of the study. This difference between the two treatment groups was notable only in the second half of the trial. <b>Conclusion:</b> The results indicate that patients with RA, by adjusting to a Mediterranean diet, did obtain a reduction in inflammatory activity, an increase in physical function, and improved vitality.
Variable Effects of Combination Corticosteroids and Catecholamines on Total β2-Adrenergic Receptors in Human CD4+ T-Lymphocytes
Authors: A.N. Salicru, B.E. Crucian, M.A. Nelman-Gonzales, J.K. Actor, C.F. Sams, G.D. Marshall
Journal: Journal of Allergy and Clinical Immunology (2007)
Maintenance of Glomerular Filtration Barrier Integrity Requires Laminin α5
Authors: Seth Goldberg, Tracy L. Adair-Kirk, Robert M. Senior, Jeffrey H. Miner
Journal: Journal of the American Society of Nephrology (2010)

Mutation of the mouse laminin α5 gene results in a variety of developmental defects, including defects in kidney structure and function. Whereas the total absence of laminin α5 results in breakdown of the glomerular basement membrane (GBM) and failed glomerular vascularization, a hypomorphic Lama5 mutation (the Lama5neo allele) results in proteinuria, hematuria, polycystic kidney disease (PKD), and death 3 to 4 weeks after birth. Here, we examined the role of podocyte-derived laminin α5 via podocyte-specific inactivation of Lama5 and podocyte-specific rescue of the Lama5neo mutation. Podocyte-specific inactivation of Lama5 resulted in varying degrees of proteinuria and rates of progression to nephrotic syndrome. The GBM of proteinuric mice appeared thickened and “moth-eaten,” and podocyte foot processes became effaced. Podocyte-specific restoration of laminin α5 production using two distinct strategies in Lama5neo/neo mice resulted in the resolution of proteinuria, hematuria, and PKD. These results suggest that the development of normal GBM structure and function requires podocyte-derived laminin α5 during and after glomerulogenesis and present a unique mechanism for the pathogenesis of PKD in these mice.