tbuckley/cabot-search huggingface dataset:
Carbonic Anhydrase IX Expression in Clear Cell Renal Cell Carcinoma and Normal Tissues: Experiences From (Radio) Immunotherapy
Authors: Adrienne H. Brouwers, Peter F.A. Mulders, Wim J.G. Oyen
Journal: Journal of Clinical Oncology (2008)

published the results of a large cohort of patients (n ϭ 730) with sporadic clear cell renal cell carcinoma (ccRCC) that was analyzed for the possible relationship between expression of carbonic anhydrase IX (CAIX) and outcome.Although they used the cut point criteria for CAIX tumor expression identified previously by Bui et al, 2,3 they could not confirm the results of the University of California, Los Angeles group, who reported that in metastatic RCC low (Յ 85%) CAIX staining is an independent poor prognostic factor for survival. 2Although low CAIX expression was associated with increased risk of death as a result of RCC in an univariate analysis, after adjusting for nuclear grade or coagulative tumor necrosis, this was no longer the case. 1 Also in their study, Leibovich et al 1 determined CAIX expression in a wide variety of normal tissues and a few other tissues.They report, "CAIX expression was present in gastric mucosa, pancreatobiliary epithelium, and small intestine crypt base.Also, CAIX was seen in two specimens containing mesothelial cells, ovarian surface epithelium, and fetal rete testis."According to the authors, the CAIX expression levels in various normal tissues are high.Therefore, they raised the question of whether CAIX-directed therapeutic strategies will have a safe enough toxicity profile, while pointing also to the literature of anti-CAIX monoclonal antibody-based therapy that have not caused significant toxicities thus far. 1 We would like to comment on these two matters specifically.Regarding CAIX expression in normal tissues, it has been reported previously by other groups, in addition to the article by Leibovich et al 1 and the studies they refer to by Ivanov et al. [4][5][6] Furthermore, from the article, it does not become clear how the high expression in the various normal tissues is related to the high CAIX expression for which most ccRCC tumors are known.In our opinion, this is relevant information in light of a discussion on the toxicity profile.6][7] Furthermore, because CAIX expression is regulated by the transcription factor HIF-1␣ that in turn is regulated (among others) by the protein Von Hippel-Lindau (VHL), and because ccRCC is molecularly characterized by (functional) loss of the VHL gene, this explains the ubiquitous CAIX expression in ccRCC. 7,8n contrast, the CAIX expression in non-RCC tumors is the result of locoregional hypoxia, leading to locoregional CAIX expression. 8egarding the toxicity profile of anti-CAIX-directed therapy with monoclonal antibodies, we point out that we have ample experi-
Use of Epoetin in Patients With Cancer: Evidence-Based Clinical Practice Guidelines of the American Society of Clinical Oncology and the American Society of Hematology
Authors: J. Douglas Rizzo, Alan E. Lichtin, Steven H. Woolf, Jerome Seidenfeld, Charles L. Bennett, David Cella, Benjamin Djulbegovic, Matthew J. Goode, Ann A. Jakubowski, Stephanie J. Lee, Carole B. Miller, Mark U. Rarick, David H. Regan, George P. Browman, Michael S. Gordon
Journal: Journal of Clinical Oncology (2002)

Anemia resulting from cancer, or its treatment, is an important clinical problem increasingly treated with the recombinant hematopoietic growth factor erythropoietin. To address uncertainties regarding indications and efficacy, the American Society of Clinical Oncology and the American Society of Hematology developed an evidence-based clinical practice guideline for the use of epoetin in patients with cancer. The guideline panel found good evidence to recommend use of epoetin as a treatment option for patients with chemotherapy-associated anemia with a hemoglobin level less than 10 g/dL. Use of epoetin for patients with less severe anemia (hemoglobin < 12 g/dL but never below 10 g/dL) should be determined by clinical circumstances. Good evidence from clinical trials supports the use of subcutaneous epoetin thrice weekly (150 U/kg tiw) for a minimum of 4 weeks. Less strong evidence supports an alternative weekly (40,000 U/wk) dosing regimen, based on common clinical practice. With either administration schedule, dose escalation should be considered for those not responding to the initial dose. In the absence of response, continuing epoetin beyond 6 to 8 weeks does not appear to be beneficial. Epoetin should be titrated once the hemoglobin concentration reaches 12 g/dL. Evidence from one randomized controlled trial supports use of epoetin for patients with anemia associated with low-risk myelodysplasia not receiving chemotherapy; however, there are no published high-quality studies to support its use for anemia in other hematologic malignancies in the absence of chemotherapy. Therefore, for anemic patients with hematologic malignancies, it is recommended that physicians initiate conventional therapy and observe hematologic response before considering use of epoetin.
Supraventricular pacemaker activity in the canine heart: Contributions from HCN channels in control conditions and in a model of heart failure
Authors: W GILES
Journal: Cardiovascular Research (2005)

See also article by Zicha et al.  [1]  (the Nattel Research Group) (pages 472–481) in this issue. 

An interesting and clearly presented paper from the Nattel Research Group [1] in this volume of Cardiovascular Research provides new evidence for the expression of three isoforms of hyperpolarization-activated cyclic nucleotide-gated ion channels (HCN) in the sinoatrial node and atria of the adult canine heart. These measurements have been made under control conditions, and in the setting of a model of congestive heart failure–tachycardia-induced sinus node dysfunction.

A major premise of this study is that although it is well-known that transmembrane ionic currents generated by HCN ion channels contribute to pacemaker activity, there appear to be significant species differences, and little information on this topic is available for the canine heart. The adult canine is a useful model for making control measurements and then studying selected pathophysiological paradigms which may be relevant to human clinical cardiac electrophysiology and to heart failure [2–5].

The immunohistochemical, molecular, and protein biochemical analyses in this paper show that in this canine model, myocytes from within the sinoatrial node region express the isoforms of this current which have been denoted HCN1, HCN2, and HCN4, with HCN2 and HCN4 predominating. Under control conditions, somewhat similar patters of results are obtained from the right atrium. Interestingly, however, in preparations from animals in which congestive heart failure was induced by overdrive pacing, the pattern of HCN expression in the sinoatrial node showed a …
Childhood NAFLD: a ticking time-bomb?
Authors: V. Nobili, C. Day
Journal: Gut (2009)

Non-alcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease in both children and adults and threatens to become a serious public health problem worldwide.1 2 It is closely associated with obesity and insulin resistance and encompasses a spectrum of disease ranging from simple fatty liver (steatosis), through necroinflammation to fibrosis and cirrhosis,3 Despite its undoubted importance, perhaps surprisingly, to date there is a paucity of data on the change in prevalence of NAFLD within a population over time, and no convincing data on either the incidence of NAFLD, or on the long-term survival of children with NAFLD.

This latter gap in the literature has now been partly filled by the study by Feldstein and colleagues4, published in this issue of Gut (see page 1538) , which describes the long-term outcomes and survival of children with NAFLD followed up for 20 years. The strength of the conclusions arising from the study is limited by its retrospective design, the low number of patients undergoing liver biopsy (7.5%) and …
Phase III trial of CHOP-21 versus CHOP-14 for aggressive non-Hodgkin’s lymphoma: final results of the Japan Clinical Oncology Group Study, JCOG 9809
Authors: K. Ohmachi, K. Tobinai, Y. Kobayashi, K. Itoh, M. Nakata, T. Shibata, Y. Morishima, M. Ogura, T. Suzuki, R. Ueda, K. Aikawa, S. Nakamura, H. Fukuda, M. Shimoyama, T. Hotta
Journal: Annals of Oncology (2011)
Mitochondria-Targeted Peptide Accelerates ATP Recovery and Reduces Ischemic Kidney Injury
Authors: Hazel H. Szeto, Shaoyi Liu, Yi Soong, Dunli Wu, Shaun F. Darrah, Feng-Ying Cheng, Zhihong Zhao, Michael Ganger, Clara Y. Tow, Surya V. Seshan
Journal: Journal of the American Society of Nephrology (2011)

The burst of reactive oxygen species (ROS) during reperfusion of ischemic tissues can trigger the opening of the mitochondrial permeability transition (MPT) pore, resulting in mitochondrial depolarization, decreased ATP synthesis, and increased ROS production. Rapid recovery of ATP upon reperfusion is essential for survival of tubular cells, and inhibition of oxidative damage can limit inflammation. SS-31 is a mitochondria-targeted tetrapeptide that can scavenge mitochondrial ROS and inhibit MPT, suggesting that it may protect against ischemic renal injury. Here, in a rat model of ischemia-reperfusion (IR) injury, treatment with SS-31 protected mitochondrial structure and respiration during early reperfusion, accelerated recovery of ATP, reduced apoptosis and necrosis of tubular cells, and abrogated tubular dysfunction. In addition, SS-31 reduced medullary vascular congestion, decreased IR-mediated oxidative stress and the inflammatory response, and accelerated the proliferation of surviving tubular cells as early as 1 day after reperfusion. In summary, these results support MPT as an upstream target for pharmacologic intervention in IR injury and support early protection of mitochondrial function as a therapeutic maneuver to prevent tubular apoptosis and necrosis, reduce oxidative stress, and reduce inflammation. SS-31 holds promise for the prevention and treatment of acute kidney injury.
Expression of Ia antigens on hapten-specific B cells. I. Delineation of B-cell subpopulations.
Authors: J L Press, N R Klinman, H O McDevitt
Journal: The Journal of Experimental Medicine (1976)

The nonimmune adult spleen contains at least two B-cell subpopulations. The majority of primary B cells express cell surface Ia determinants and have the capacity to give rise to IgG antibody-producing clones after T-cell dependent antigenic stimulation. There is also a small subpopulation of primary B cells which are, by definition, Ia negative, since their activity is not eliminated by negative selection with anti-Ia serum and complement. The Ia-negative B cells give rise to clones that produce only IgM antibody. These B-cell subsets may form a continuum in B-cell maturation, or they may exist as discrete B-cell lineages. Since the cellular expression of Ia antigens appears to correlate with the ability of the B cell to generate IgG-producing clones, it is speculated that Ia molecules may have a role in the IgM to IgG B-cell switch mechanism.
VALUE AND LIMITATIONS OF A PSYCHIATRIC DEPARTMENT IN A GENERAL HOSPITAL IN BOMBAY (INDIA)
Authors: N. S. VAHIA
Journal: American Journal of Psychiatry (1959)

1. Considering the stigma associated with mental hospitals, the psychiatric department of a general hospital is a much better place, not only for detection and treatment of early cases of psychosis, but also for various kinds of psychoneurosis. 2. As a much wider variety of cases of psychiatric illnesses attended the psychiatric department of a general hospital it is a good place not only for diagnosis and treatment of these illnesses, but also for teaching purposes. 3. Importance of psychiatry as an integral part of general medicine is well recognized by general medical practitioners and also by specialists in other branches of medicine; at least in the larger cities in our country. What is probably not appreciated is the need for early recognition of these cases and for treatment in the early stages to obtain better results. 4. Limitations of this department were very conspicuous in this study. A greater number of trained personnel and more beds are urgently needed for both treatment and teaching purposes. 5. In our country, the establishment of psychiatric departments in general hospitals with adequate staff and beds is urgently needed to serve the community more efficiently and to develop healthy attitudes towards mental illness.
Interactions of <i>IL-12A</i> and <i>IL-12B</i> Polymorphisms on the Risk of Cervical Cancer in Chinese Women
Authors: Xiaojun Chen, Suping Han, Sumin Wang, Xiaoyi Zhou, Mingfeng Zhang, Jing Dong, Xiaoyan Shi, Nianfeng Qian, Xinru Wang, Qingyi Wei, Hongbing Shen, Zhibin Hu
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Accumulative evidence suggests that interleukin-12 (IL-12) plays a central role in the Th1 responses and thus participates in the carcinogenesis of human papillomavirus–related cervical cancer. We hypothesized that potentially functional polymorphisms in IL12A and IL12B may individually and jointly contribute to cervical cancer risk. Experimental Design: We genotyped IL12A rs568408 [3′ untranslated region (UTR) G&amp;gt;A] and rs2243115 (5′UTR T&amp;gt;G) and IL12B rs3212227 (3′UTR A&amp;gt;C) in a hospital-based study of 404 cervical cancer cases and 404 cancer-free controls. Results: The IL12A rs568408 GA/AA and IL12B rs3212227 AC/CC variant genotypes were associated with a significantly increased risk of cervical cancer [adjusted odds ratio, 1.43; 95% confidence interval (CI), 1.06-1.93; and adjusted odds ratio, 1.30; 95% CI, 0.97-1.75, respectively], compared with their corresponding wild-type homozygotes. Moreover, a significant gene-gene interaction of these 2 loci were evident in the risk of cervical cancer, and subjects carrying variant genotypes of both loci had a 1.82-fold (95% CI, 1.28-2.57) increased risk of cervical cancer. In the stratified analyses, the combined genetic effect was more pronounced in patients who had early-stage tumors or more parities. Subjects carrying rs568408 AG/AA and rs3212227 AC/CC genotypes and having &amp;gt;2 parities showed a 6.00-fold (95% CI, 2.86-12.56) elevated cervical cancer risk (P for multiplicative interaction = 0.046). Conclusion: These findings suggest that IL12A rs568408 and IL12B rs3212227 may individually and jointly contribute to the risk of cervical cancer and may modify cervical cancer risk associated with parity, but these data need further validation.
Teenage pregnancy rates: high compared with where and when?
Authors: D. A Lawlor, M. Shaw
Journal: Journal of the Royal Society of Medicine (2004)

In the past decade teenage pregnancy has become a key policy area in several industrialized countries. During the 1990s, both Britain and the USA identified teenage pregnancy as a national public health issue, alongside cardiovascular disease, cancer and mental health, requiring targeted interventions.1,2 A reason for this concern was that rates of teenage pregnancy were perceived to be higher than those in other developed countries2,3—a notion that has been taken up and inflated by the media. For example:


`Britain... has a sky-high level of teenage pregnancies.' [Daily Mail, 8 March 2001]

`The sexual behaviour of our children and teenagers has now reached such unprecedented levels of recklessness and damage that it is becoming a horror story running out of control.' [Daily Mail 28 June 2002]


In our opinion, such claims are based on selective comparisons. Here we argue that, contrary to the way in which it is frequently presented, the teenage pregnancy rate in Britain is neither high nor dramatically increasing.
Salivary gland and peripheral blood T helper 1 and 2 cell activity in Sjogren's syndrome compared with non-Sjogren's sicca syndrome
Authors: J M van Woerkom
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objectives:</b> To investigate whether differences in T helper (Th) 1 and Th2 cell activity in salivary glands ("local") or ("peripheral") blood can discriminate between Sjögren's syndrome (SS) and non-Sjögren's sicca syndrome (nSS-sicca). Additionally, to study relationships of local and peripheral Th cell activities with each other and with disease activity measures. <b>Methods:</b> 62 sicca patients (32 with SS, 30 with nSS-sicca) were studied. Local Th1 (interferon γ (IFNγ)) and Th2 (interleukin (IL) 4) activity were determined using immunohistochemistry. T cell production of IFNγ and IL4 in peripheral blood (PB) was determined by ELISA. Erythrocyte sedimentation rate (ESR) and serum IgG were considered disease activity measures. <b>Results:</b> ESR and serum IgG were higher in patients with SS than in patients with nSS-sicca. Local Th1 cell activity was higher and PB Th1 activity lower in patients with SS than in those with nSS-sicca. Th2 cell activity did not differ significantly between the patient groups. The ratio IFNγ/IL4 was higher in salivary glands and lower in PB in patients with SS than in patients with nSS-sicca. Local and peripheral Th1 and Th2 cell activities correlated with ESR and serum IgG levels. ESR, serum IgG, and local or peripheral Th1 or Th2 cell activity did not discriminate between patients with SS and nSS-sicca. <b>Conclusions:</b> An imbalance between Th1 and Th2 activity in sicca patients is clearly related to the severity of disease, but cannot be used to distinguish between patients with SS and those with nSS-sicca.
The antiinflammatory activity of IgG: the intravenous IgG paradox
Authors: Falk Nimmerjahn, Jeffrey V. Ravetch
Journal: The Journal of Experimental Medicine (2007)

How high doses of intravenous IgG (IVIG) suppress autoimmune diseases remains unresolved. We have recently shown that the antiinflammatory activity of IVIG can be attributed to a minor species of IgGs that is modified with terminal sialic acids on their Fc-linked glycans. Here we propose that these Fc-sialylated IgGs engage a unique receptor on macrophages that, in turn, leads to the upregulation of an inhibitory Fcγ receptor (FcγR), thereby protecting against autoantibody-mediated pathology.
The Selective Estrogen Receptor Modulator Arzoxifene and the Rexinoid LG100268 Cooperate to Promote Transforming Growth Factor β-Dependent Apoptosis in Breast Cancer
Authors: Mara H. Rendi, Nanjoo Suh, William W. Lamph, Stan Krajewski, John C. Reed, Richard A. Heyman, Andrew Berchuck, Karen Liby, Renee Risingsong, Darlene B. Royce, Charlotte R. Williams, Michael B. Sporn
Journal: Cancer Research (2004)

Abstract We show that the selective estrogen receptor modulator arzoxifene (Arz) and the rexinoid LG100268 (268) synergize to promote apoptosis in a rat model of estrogen receptor-positive breast carcinoma and in estrogen receptor-positive human breast cancer cells in culture. We also show that it is not necessary to administer Arz and 268 continuously during tumor progression to prevent cancer in the rat model because dosing of these drugs in combination for relatively short periods, each followed by drug-free rests, is highly effective. This new approach to chemoprevention uses high doses of drugs that are too toxic for long-term administration. However, when given for short periods, the agents are nontoxic and still induce apoptosis in breast cancer cells. We also show that the ability of the two drugs to induce apoptosis is the combined result of induction of transforming growth factor β by Arz, together with inhibition of the prosurvival nuclear factor κB and phosphatidylinositol 3′ kinase signaling pathways by 268. The new protocol we have developed for chemoprevention allows the efficacious and safe administration of 268 and Arz, and these agents now should be considered for clinical use.
<i>Cis-</i>Regulatory Changes Associated with a Recent Mating System Shift and Floral Adaptation in<i>Capsella</i>
Authors: Kim A. Steige, Johan Reimegård, Daniel Koenig, Douglas G. Scofield, Tanja Slotte
Journal: Molecular Biology and Evolution (2015)

The selfing syndrome constitutes a suite of floral and reproductive trait changes that have evolved repeatedly across many evolutionary lineages in response to the shift to selfing. Convergent evolution of the selfing syndrome suggests that these changes are adaptive, yet our understanding of the detailed molecular genetic basis of the selfing syndrome remains limited. Here, we investigate the role of cis-regulatory changes during the recent evolution of the selfing syndrome in Capsella rubella, which split from the outcrosser Capsella grandiflora less than 200 ka. We assess allele-specific expression (ASE) in leaves and flower buds at a total of 18,452 genes in three interspecific F1 C. grandiflora x C. rubella hybrids. Using a hierarchical Bayesian approach that accounts for technical variation using genomic reads, we find evidence for extensive cis-regulatory changes. On average, 44% of the assayed genes show evidence of ASE; however, only 6% show strong allelic expression biases. Flower buds, but not leaves, show an enrichment of cis-regulatory changes in genomic regions responsible for floral and reproductive trait divergence between C. rubella and C. grandiflora. We further detected an excess of heterozygous transposable element (TE) insertions near genes with ASE, and TE insertions targeted by uniquely mapping 24-nt small RNAs were associated with reduced expression of nearby genes. Our results suggest that cis-regulatory changes have been important during the recent adaptive floral evolution in Capsella and that differences in TE dynamics between selfing and outcrossing species could be important for rapid regulatory divergence in association with mating system shifts.
The squirting bleb: image and treatment of inspiration-linked leakage of a peritoneopleural fistula
Authors: F H Krouwels
Journal: Thorax (2004)

A 25 year old man with known chronic right sided heart failure and ascites due to a congenital heart defect presented with dyspnoea and a massive pleural effusion. Thoracoscopy revealed two diaphragmatic blebs. Changes in peritoneal and thoracic pressure during respiration resulted in periodic squirting of a ruptured bleb, illustrating preferential flow of peritoneal fluid into the thorax. The pleural effusion was successfully treated with drainage of ascitic fluid and chemical pleurodesis.
General Cortical and Special Prefrontal Connections: Principles from Structure to Function
Authors: Helen Barbas
Journal: Annual Review of Neuroscience (2015)

How is the vast brain communication system organized? A structural model relates connections to laminar differences between linked areas. The model is based on the principle of systematic structural variation in the cortex, extending from the simplest limbic cortices to eulaminate areas with elaborate lamination. The model accounts for laminar patterns and for the strength and topography of connections between nearby or distant cortices and subcortical structures, exemplified quantitatively for the principal and special prefrontal connections. Widespread connections of limbic areas and focal connections of eulaminate areas yield a broad range of circuit patterns for diverse functions. These diverse pathways innervate excitatory and functionally distinct inhibitory neurons, providing the basis for differential recruitment of areas for flexible behavior. Systematic structural variation likely emerges by timing differences in the development of distinct areas and has important implications for altered connections in diseases of developmental origin.