tbuckley/cabot-search huggingface dataset:
Pentostatin in chronic lymphocytic leukemia: a phase II trial of Cancer and Leukemia group B.
Authors: R O Dillman, R Mick, O R McIntyre
Journal: Journal of Clinical Oncology (1989)

We conducted a phase II trial of deoxycoformycin (pentostatin [DCF]) in chronic lymphocytic leukemia (CLL). Eligibility criteria included age greater than 18 years, Cancer and Leukemia Group B (CALGB) performance status 0 to 2, lymphocyte count greater than or equal to 15,000 cells/microL, international stage B or C disease (multiple lymph nodes involved and/or hemoglobin [Hgb] less than 11 g and/or platelets less than 100,000/microL) and no more than one prior treatment regimen. DCF dose was 4 mg/m2 intravenously (IV) weekly for 3 weeks and then every 2 weeks. There were 39 eligible patients (35 men and four women; median age, 63 years; median time from diagnosis to study entry, 3 years). Of these 39 patients, 31% were stage B and 33% had no prior treatment. Median laboratory values at entry were Hgb 10.5 g, WBC 96,100/microL, and platelets 93,500/microL. Nodal involvement was present in 90%, splenomegaly in 81%, and hepatomegaly in 47%. Patients received a median of nine DCF injections, with a range of four to 26. Three patients were not evaluable for response. Overall, 3% achieved a complete response (CR), 23% a partial response (PR), 28% showed clinical improvement (CI), and 38% had stable disease (SD). Associated toxicities (grade 2 or worse) observed were infections (52%), worsening of thrombocytopenia (26%) or anemia (33%), nausea and vomiting (31%), rash or pruritus (20%), and stomatitis (8%). We conclude that DCF is an active agent in CLL with acceptable toxicity.
High Blood Pressure in the Young
Authors: G S Berenson, J L Cresanta, L S Webber
Journal: Annual Review of Medicine (1984)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
P1144 : Hepatocyte specific expression of a dominant stable form of beta-catenin results in cholestatic liver disease
Authors: U.J. Lemberger, C. Fuchs, M. Karer, C. Schöfer, T. Stojakovic, F. Wrba, M.M. Taketo, M. Trauner, C.H. Österreicher
Journal: Journal of Hepatology (2015)
The Pathology and Treatment of Cholera
Authors: G. Johnson
Journal: BMJ (1871)

GENTLEMEN,-I beg to acknowledge the compliment that has been paid me in asking me to take this chair, and to preside over the proceedings of this Section.I must presume that the offer was made to me in recognition of the social position which I occupy by the indul- gence of my fellow-townsmen, and not from any claim that I may present to the Association personally.I will not detain you by any lengthened remarks upon tile subject of surgery.After the able ad- dress that was delivered to us this morning by Dr. Johnson, perhaps it would be better that we should come almost immediately to the actual business of the Section.However, I may observe that, whilst hearing Dr. Johnson this morning remark upon the great changes that had gone on in medicine within the last thirty years, I recalled the fact that I myself was old enough to recollect that within the same period enor- mous advances have been made in surgery also.I can look back and recognise in my younger days such great names as those of Astley Cooper and Abernethy, besides others with which we are all familiar as being leaders of the profession in their day and generation.If we compare their opinions and their practice with those of the present day, we are at once reminded of the great advance that has been made.
Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis
Authors: Leticia Monin, Kristin L. Griffiths, Wing Y. Lam, Radha Gopal, Dongwan D. Kang, Mushtaq Ahmed, Anuradha Rajamanickam, Alfredo Cruz-Lagunas, Joaquín Zúñiga, Subash Babu, Jay K. Kolls, Makedonka Mitreva, Bruce A. Rosa, Rosalio Ramos-Payan, Thomas E. Morrison, Peter J. Murray, Javier Rangel-Moreno, Edward J. Pearce, Shabaana A. Khader
Journal: Journal of Clinical Investigation (2015)

Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1-expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1-expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB.
Light Chain Proximal Tubulopathy: Clinical and Pathologic Characteristics in the Modern Treatment Era
Authors: Michael B. Stokes, Anthony M. Valeri, Leal Herlitz, Abdullah M. Khan, David S. Siegel, Glen S. Markowitz, Vivette D. D’Agati
Journal: Journal of the American Society of Nephrology (2015)

Light chain proximal tubulopathy (LCPT) is characterized by cytoplasmic inclusions of monoclonal LC within proximal tubular cells. The significance of crystalline versus noncrystalline LCPT and the effect of modern therapies are unknown. We reported the clinical-pathologic features of 40 crystalline and six noncrystalline LCPT patients diagnosed between 2000 and 2014. All crystalline LCPTs were κ-restricted and displayed acute tubular injury. One-third of noncrystalline LCPT patients displayed λ-restriction or acute tubular injury. Only crystalline LCPT frequently required antigen retrieval to demonstrate monoclonal LC by immunofluorescence. In five of 38 patients, crystals were not detectable by light microscopy, but they were visible by electron microscopy. Hematolymphoid neoplasms, known before biopsy in only 15% of patients, included 21 monoclonal gammopathies of renal significance; 15 multiple myelomas; seven smoldering multiple myelomas; and three other neoplasms. Biopsy indications included Fanconi syndrome (38%; all with crystalline LCPT), renal insufficiency (83%), and proteinuria (98%). Follow-up was available for 30 (75%) patients with crystalline LCPT and all six patients with noncrystalline LCPT, of whom 11 underwent stem cell transplant, 16 received chemotherapy only, and nine were untreated. Complete or very good partial hematologic remissions occurred in six of 22 treated crystalline LCPT patients. By multivariable analysis, the only independent predictor of final eGFR was initial eGFR, highlighting the importance of early detection. All patients with crystalline LCPT treated with stem cell transplant had stable or improved kidney function, indicating the effectiveness of aggressive therapy in selected patients.
Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways
Authors: Darcy R. Denner, Naseer Sangwan, Julia B. Becker, D. Kyle Hogarth, Justin Oldham, Jamee Castillo, Anne I. Sperling, Julian Solway, Edward T. Naureckas, Jack A. Gilbert, Steven R. White
Journal: Journal of Allergy and Clinical Immunology (2015)
Gesture, sign, and language: The coming of age of sign language and gesture studies
Authors: Susan Goldin-Meadow, Diane Brentari
Journal: Behavioral and Brain Sciences (2015)

How does sign language compare with gesture, on the one hand, and spoken language on the other? Sign was once viewed as nothing more than a system of pictorial gestures without linguistic structure. More recently, researchers have argued that sign is no different from spoken language, with all of the same linguistic structures. The pendulum is currently swinging back toward the view that sign is gestural, or at least has gestural components. The goal of this review is to elucidate the relationships among sign language, gesture, and spoken language. We do so by taking a close look not only at how sign has been studied over the past 50 years, but also at how the spontaneous gestures that accompany speech have been studied. We conclude that signers gesture just as speakers do. Both produce imagistic gestures along with more categorical signs or words. Because at present it is difficult to tell where sign stops and gesture begins, we suggest that sign should not be compared with speech alone but should be compared with speech-plus-gesture. Although it might be easier (and, in some cases, preferable) to blur the distinction between sign and gesture, we argue that distinguishing between sign (or speech) and gesture is essential to predict certain types of learning and allows us to understand the conditions under which gesture takes on properties of sign, and speech takes on properties of gesture. We end by calling for new technology that may help us better calibrate the borders between sign and gesture.
Efficacy of C1-Inhibitor Concentrate (Berinert®) for the Treatment of Cutaneous Attacks of Acute Hereditary Angioedema Compared to Historical Untreated Controls
Authors: Konrad Bork, Petra Staubach, Jonathan A. Bernstein, Henrike Feuersenger, Thomas Machnig, Timothy J. Craig
Journal: Journal of Allergy and Clinical Immunology (2013)
Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer.
Authors: N T Ueno, G Rondón, N Q Mirza, D K Geisler, P Anderlini, S A Giralt, B S Andersson, D F Claxton, J L Gajewski, I F Khouri, M Körbling, R C Mehra, D Przepiorka, Z Rahman, B I Samuels, K van Besien, G N Hortobagyi, R E Champlin
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the feasibility of allogeneic peripheral-blood progenitor-cell (PBPC) transplantation and to assess graft-versus-tumor effects in patients with metastatic breast cancer. PATIENTS AND METHODS Ten patients with metastatic breast cancer that involved the liver or bone marrow were treated with high-dose chemotherapy and allogeneic PBPC transplantation. The median age was 42 years (range, 29 to 55). The median number of metastatic sites was three (range, one to five). The conditioning regimen was cyclophosphamide (6,000 mg/m2), carmustine (BCNU; 450 mg/m2), and thiotepa (720 mg/m2) (CBT regimen). Patients received graft-versus-host disease (GVHD) prophylaxis using cyclosporine- or tacrolimus-based regimens. RESULTS All patients had engraftment and hematologic recovery. Three patients developed grade &gt; or = 2 acute GVHD and four patients had chronic GVHD. After transplantation, one patient was in complete remission (CR), five achieved a partial remission (PR), and four had stable disease (SD). In two patients, metastatic liver lesions regressed in association with skin GVHD after withdrawal of immunosuppressive therapies. The median follow-up time was 408 days (range, 53 to 605). The median progression-free survival duration was 238 days (range, 53 to 510). CONCLUSION We conclude that allogeneic PBPC transplantation is a feasible procedure for patients with poor-risk metastatic breast cancer. The regression of tumor associated with GVHD provides suggestive clinical evidence that graft-versus-tumor effects may occur against breast cancer. Compared with autologous transplantation, allogeneic PBPC transplantation is associated with the additional risks of GVHD and related infections. Allogeneic transplantation should only be performed in the context of clinical trials and its ultimate role requires demonstration of improved progression-free survival.
Immunologic Aspects of Schistosomiasis
Authors: A Capron, J P Dessaint
Journal: Annual Review of Medicine (1992)

Immunity to schistosomes, helminth worms that infect 200 million people, is targeted to invading larvae (concomitant immunity). In vitro studies have revealed the role of T cells and of particular antibody isotypes in immune defense: IgE antibody cooperates with mononuclear phagocytes, eosinophils, and platelets to kill schistosome larvae. IgE antibody appears as an essential component of acquired resistance in rats. The role of IgE antibody has recently been confirmed by epidemiological studies demonstrating a positive correlation between the acquisition of resistance to reinfection by schistosomes and the level of IgE antibody to the parasite. A negative correlation found in these studies with the levels of IgM, IgG2, or IgG4 antibodies could be related to the development of a blocking antibody response. Antigens involved in protective immunity are expressed transiently at the surface of schistosomes. Sm28, a glutathione-S-transferase, induces significant protection against schistosome infection in rodents and nonhuman primates. In addition, this vaccine reduces the size of egg granulomas and egg output. Besides allowing the definition of a vaccine strategy against a major disease, studies on immunology of schistosomiasis have unraveled unsuspected antigenic mimicry between schistosomes and HIV regulatory proteins and have led to the demonstration that IgE antibody, a protective isotype against helminths, may also activate Fc epsilon-RII-bearing mononuclear phagocytes, eosinophils, and platelets in allergic disease.
KDR Amplification Is Associated with VEGF-Induced Activation of the mTOR and Invasion Pathways but does not Predict Clinical Benefit to the VEGFR TKI Vandetanib
Authors: Monique B. Nilsson, Uma Giri, Jayanthi Gudikote, Ximing Tang, Wei Lu, Hai Tran, Youhong Fan, Andrew Koo, Lixia Diao, Pan Tong, Jing Wang, Roy Herbst, Bruce E. Johnson, Andy Ryan, Alan Webster, Philip Rowe, Ignacio I. Wistuba, John V. Heymach
Journal: Clinical Cancer Research (2015)

Abstract Purpose: VEGF pathway inhibitors have been investigated as therapeutic agents in the treatment of non–small cell lung cancer (NSCLC) because of its central role in angiogenesis. These agents have improved survival in patients with advanced NSCLC, but the effects have been modest. Although VEGFR2/KDR is typically localized to the vasculature, amplification of KDR has reported to occur in 9% to 30% of the DNA from different lung cancers. We investigated the signaling pathways activated downstream of KDR and whether KDR amplification is associated with benefit in patients with NSCLC treated with the VEGFR inhibitor vandetanib. Methods: NSCLC cell lines with or without KDR amplification were studied for the effects of VEGFR tyrosine kinase inhibitors (TKI) on cell viability and migration. Archival tumor samples collected from patients with platinum-refractory NSCLC in the phase III ZODIAC study of vandetanib plus docetaxel or placebo plus docetaxel (N = 294) were screened for KDR amplification by FISH. Results: KDR amplification was associated with VEGF-induced activation of mTOR, p38, and invasiveness in NSCLC cell lines. However, VEGFR TKIs did not inhibit proliferation of NSCLC cell lines with KDR amplification. VEGFR inhibition decreased cell motility as well as expression of HIF1α in KDR-amplified NSCLC cells. In the ZODIAC study, KDR amplification was observed in 15% of patients and was not associated with improved progression-free survival, overall survival, or objective response rate for the vandetanib arm. Conclusions: Preclinical studies suggest KDR activates invasion but not survival pathways in KDR-amplified NSCLC models. Patients with NSCLC whose tumor had KDR amplification were not associated with clinical benefit for vandetanib in combination with docetaxel. Clin Cancer Res; 22(8); 1940–50. ©2015 AACR.
Prevalence and Timing of Screening and Diagnostic Testing for Gestational Diabetes Mellitus: A Population-Based Study in Alberta, Canada
Authors: Lois E. Donovan, Anamaria Savu, Alun L. Edwards, Jeffrey A. Johnson, Padma Kaul
Journal: Diabetes Care (2015)

OBJECTIVE The extent to which pregnant women are screened for gestational diabetes mellitus (GDM) at the population level is not known. We examined the rate, type, and timing of GDM screening and diagnostic testing in the province of Alberta, Canada. Geographic and temporal differences in screening rates, and maternal risk factors associated with lower likelihood of screening, were also determined. RESEARCH DESIGN AND METHODS Our retrospective linked-database cohort study included 86,842 primiparous women with deliveries between 1 October 2008 and 31 December 2012. Multivariable logistic regression analysis was used to examine maternal factors associated with lower likelihood of GDM screening. RESULTS Overall, 94% (n = 81,304) of women underwent some form of glycemic assessment in the 270 days prior to delivery. The majority (91%) received a 50-g glucose screen (GDS). Women not screened were younger and more likely to smoke and had lower maternal weight and median household income. When a diagnostic 75-g oral glucose tolerance test (OGTT) was indicated, it occurred a median of 10 (interquartile range 7, 15) days after the screen. CONCLUSIONS GDS occurred widely in a system where it was universally recommended and paid for publicly. When indicated, a 75-g OGTT was completed within 15 days in 75% of cases. Our finding that this two-step approach was widely implemented in a timely fashion supports continued endorsement of a two-step approach to screening and diagnosis of GDM. Further research is merited to assess whether the one-step GDM diagnostic approach results in different rates and timing of the 75-g OGTT and affects pregnancy outcomes.
Management of Children with Progressive Renal Failure
Authors: John T. Herrin
Journal: Annual Review of Medicine (1983)

The strategy of management in childhood renal failure is to integrate available therapeutic modalities with the natural history of the disease in such a manner that linear growth is preserved. Attention to psychosocial growth is necessary for full rehabilitation. Treatment is ordered to provide hope and confidence to family and patient. Conservative medical therapy provides chemical stabilization and prophylaxis against bone disease and growth retardation. Planned progression to replacement of renal function by dialysis or renal transplant is made when growth or control of bone disease is no longer possible, but before complications occur. Therapy is effective; 90% of patients survive 5-10 years with 65% retaining a functioning allograft. Full rehabilitation is attained in 85-90% of post-transplant and 50% of dialysis patients. Technical advances now allow safe dialysis for all age groups. Although growth maintenance remains a major problem, it is possible that earlier metabolic control and transplantation to protect growth in the critical early years, together with improved control of rejection, may allow close approximation to optimal growth potential.
PRC2 Epigenetically Silences Th1-Type Chemokines to Suppress Effector T-Cell Trafficking in Colon Cancer
Authors: Nisha Nagarsheth, Dongjun Peng, Ilona Kryczek, Ke Wu, Wei Li, Ende Zhao, Lili Zhao, Shuang Wei, Timothy Frankel, Linda Vatan, Wojciech Szeliga, Yali Dou, Scott Owens, Victor Marquez, Kaixiong Tao, Emina Huang, Guobin Wang, Weiping Zou
Journal: Cancer Research (2015)

Infiltration of tumors with effector T cells is positively associated with therapeutic efficacy and patient survival. However, the mechanisms underlying effector T-cell trafficking to the tumor microenvironment remain poorly understood in patients with colon cancer. The polycomb repressive complex 2 (PRC2) is involved in cancer progression, but the regulation of tumor immunity by epigenetic mechanisms has yet to be investigated. In this study, we examined the relationship between the repressive PRC2 machinery and effector T-cell trafficking. We found that PRC2 components and demethylase JMJD3-mediated histone H3 lysine 27 trimethylation (H3K27me3) repress the expression and subsequent production of Th1-type chemokines CXCL9 and CXCL10, mediators of effector T-cell trafficking. Moreover, the expression levels of PRC2 components, including EZH2, SUZ12, and EED, were inversely associated with those of CD4, CD8, and Th1-type chemokines in human colon cancer tissue, and this expression pattern was significantly associated with patient survival. Collectively, our findings reveal that PRC2-mediated epigenetic silencing is not only a crucial oncogenic mechanism, but also a key circuit controlling tumor immunosuppression. Therefore, targeting epigenetic programs may have significant implications for improving the efficacy of current cancer immunotherapies relying on effective T-cell-mediated immunity at the tumor site.
Crepuscule With Nellie
Authors: Michael Collins
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The meaning of expressed emotion: theoretical issues raised by cross- cultural research
Authors: J H Jenkins, M Karno
Journal: American Journal of Psychiatry (1992)

haviors expressed by relatives about a family member diagnosed with schizophrenia.The specific factors that make up the construct of expressed emotion are criticism, hostility, and emotional overinvolvement.Several naturalistic studies have demonstrated the association of these factors with clinical relapse (5-8).Patients living in home environments characterized by high levels of expressed emotion are significantly more likely to experience a clinical relapse than are patients residing in households with low levels of expressed emotion.This finding has not surprisingly resulted in a great deal of clinical interest in a construct originally developed
2,3,7,8-Tetrachlorodibenzo-p-Dioxin-Induced Changes in Immunocompetence: Possible Mechanisms
Authors: M P Holsapple, D L Morris, S C Wood, N K Snyder
Journal: The Annual Review of Pharmacology and Toxicology (1991)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More