tbuckley/cabot-search huggingface dataset:
Application of the freeze-fracture replication technique to investigative dermatology
Authors: A.S. BREATHNACH
Journal: British Journal of Dermatology (1973)

Journal Article Application of the freeze‐fracture replication technique to investigative dermatology Get access A.S. BREATHNACH A.S. BREATHNACH Department of Anatomy, St Mary's Hospital Medical School, London, W.2 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 88, Issue 6, 1 June 1973, Pages 563–574, https://doi.org/10.1111/j.1365-2133.1973.tb08020.x Published: 01 June 1973 Article history Accepted: 22 November 1972 Published: 01 June 1973
Long-Term Follow-Up of Children Treated for High-Grade Gliomas: Children's Oncology Group L991 Final Study Report
Authors: Stephen Alan Sands, Tianni Zhou, Sharon Helene O'Neil, Sunita K. Patel, Jeffrey Allen, Patsy McGuire Cullen, Thomas A. Kaleita, Robert Noll, Charles Sklar, Jonathan Lester Finlay
Journal: Journal of Clinical Oncology (2012)

High-grade gliomas of the CNS are characterized by poor treatment response and prognosis for long-term survival. The Children's Oncology Group (COG) L991 study investigated the neuropsychological, behavioral, and quality of life (QoL) outcomes after treatment on the Children's Cancer Group (CCG) trial for high-grade gliomas (CCG-945).Fifty-four patients (29 males, 25 females) with a median age of 8.8 years at diagnosis (range, 0.2 to 19.5 years) were enrolled at 25 institutions in North America, representing 81% of available survivors; median length of follow-up was 15.1 years (range, 9.5 to 19.2 years), and median age at study evaluation was 23.6 years (range, 11.3 to 36 years). Standardized tests of neuropsychological functioning and QoL were performed. Descriptive statistics summarized principal findings, and one-way analysis of variance identified potential predictors of outcomes.With an average follow-up time of 15 years, survivors demonstrated intellectual functioning within the low-average range. Executive functioning and verbal memory were between the low-average and borderline ranges. In contrast, visual memory and psychomotor processing speed were between the borderline and impaired ranges, respectively. Approximately 75% of patient reported overall QoL within or above normal limits for both physical and psychosocial domains. Nonhemispheric tumor location (midline or cerebellum), female sex, and younger age at treatment emerged as independent risk factors.These results serve as a benchmark for comparison with future pediatric high-grade glioma studies, in addition to identifying at-risk cohorts that warrant further research and proactive interventions to minimize late effects while striving to ensure survival.
Apurinic/apyrimidinic endonuclease1/redox factor-1 inhibits monocyte adhesion in endothelial cells
Authors: C KIM, S SON, E KIM, S KIM, D YOO, H KIM, S RYOO, S LEE, K IRANI, B JEON
Journal: Cardiovascular Research (2005)

Objective: Expression of adhesion molecules on endothelial cells and subsequent monocyte adhesion are initial events in the development of atherosclerosis. The purpose of this study was to investigate the role of apurinic/apyrmidinic endonuclease1/redox factor-1 (APE1/ref-1) in the interaction of monocytes with vascular endothelial cells. Methods: Human umbilical vein endothelial cells (HUVECs) were transfected with an adenovirus encoding human APE1/ref-1. The effect of APE1/ref-1 overexpression on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) protein expression, and intracellular superoxide production in tumor necrosis factor (TNF)-α-activated HUVECs was examined. Results: Adhesion of the monocytic cell line U937 to TNF-α-stimulated HUVECs in which APE1/ref-1 was overexpressed was suppressed. APE1/ref-1 overexpression also suppressed expression of VCAM-1 induced by TNF-α. APE1/ref-1-mediated suppression of VCAM-1 was blocked by pretreatment with the nitric oxide synthase (NOS) inhibitor l-nitroarginine methyl ester. Furthermore, APE1/ref-1 overexpression inhibited the TNF-α-induced increase in intracellular superoxide and p38 MAPK phosphorylation. Conclusions: These data provide evidence that APE1/ref-1 in endothelial cells mitigates TNF-α-induced monocyte adhesion and expression of vascular cell adhesion molecules, and this anti-adhesive property of APE1/ref-1 is primarily mediated by a NOS-dependent mechanism. Furthermore, APE1/ref-1 may inhibit VCAM-1 expression by inhibiting superoxide production and p38 MAPK activation.
Subclinical Viremia Increases Risk for Chronic Allograft Injury in Pediatric Renal Transplantation
Authors: Jodi M. Smith, Lawrence Corey, Rachel Bittner, Laura S. Finn, Patrick J. Healey, Connie L. Davis, Ruth A. McDonald
Journal: Journal of the American Society of Nephrology (2010)

The impact of subclinical viral infection on chronic allograft injury in the pediatric renal transplant population is not well defined. We prospectively assessed cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNAemia by monthly PCR in 55 pediatric renal transplant recipients for the first 2 years after transplantation. Subclinical CMV and EBV infection occurred in 22 and 36%, respectively. Multivariable linear regression analysis suggested that both subclinical CMV and EBV infection independently associate with significant declines in GFR during the first 2 years after transplantation. CMV seronegativity associated with a significantly greater decline in GFR than seropositivity (P < 0.01). Subclinical CMV infection and subclinical EBV infection each associated with approximately fourfold greater odds of histologic evidence of chronic allograft injury (odds ratio 4.61 [95% confidence interval 1.18 to 18.07] and odds ratio 4.33 [95% confidence interval 1.34 to 14.00], respectively). An increase in viral load of CMV or EBV also associated with increased risk for moderate to severe chronic allograft injury. Taken together, these results demonstrate an association between subclinical CMV and EBV infections, which occur despite standard antiviral prophylaxis, and chronic allograft injury in pediatric renal transplant recipients.
Epstein-Barr virus transformation induces B lymphocytes to produce human interleukin 10.
Authors: N Burdin, C Péronne, J Banchereau, F Rousset
Journal: The Journal of Experimental Medicine (1993)

Interleukin 10 (IL-10) is a pleiotropic factor that enhances proliferation of activated human B lymphocytes and induces them to secrete high amounts of immunoglobulins. Here we show that several human B cell lines were able to constitutively secrete human (h)IL-10. Whereas none of the pre-B nor the plasmocytic cell lines tested produced hIL-10, 25 of the 36 tested mature B cell lines (lymphoblastoid and Burkitt lymphoma cell lines) secreted hIL-10. Moreover, 24 of these 25 hIL-10-producing B cell lines contained the Epstein-Barr virus (EBV) genome, suggesting a relationship between hIL-10 production by human B cell lines and EBV expression. Accordingly, whereas polyclonal activation via triggering of surface immunoglobulins or CD40 antigen induced highly purified normal human B lymphocytes to produce only low (0.3-0.4 ng/ml) but significant amounts of hIL-10, EBV infection induced them to secrete high amounts of hIL-10 (4-9 ng/ml). Furthermore, addition of exogenous hIL-10, simultaneously to EBV infection, potentiated cell proliferation, whereas a blocking anti-IL-10 antiserum inhibited it. Thus, hIL-10 produced by infected human B lymphocytes appears to be involved in the mechanisms of EBV-induced B cell proliferation.
The relief of communication
Authors: William G Pickering
Journal: BMJ (2006)

E ven in the best of medical hands communication can be incomplete. Some time ago an acquaintance, knowing I was medical, told me that she had discovered a problem in her breast and had made an appointment to see the general practitioner. She added that she had been aware of it for some months, and asked if I thought she had been silly to wait, to which I replied evasively that I was pleased she was now seeing someone about it. This was the first of many questions she had for me.

Her “very nice” GP, of whom she had apparently asked several questions, which had been sympathetically answered, saw and referred her promptly. Within three weeks she had seen a surgeon and reported that he too was “very nice, and I liked him.” She unhesitatingly used the word cancer, although she did not say whether or not the doctors had used it; nor did I ask. “I think they …
Chromosome 6 Phylogeny in Primates and Centromere Repositioning
Authors: V. Eder
Journal: Molecular Biology and Evolution (2003)

A panel of 15 human BAC/PAC probes, covering the entire chromosome 6, was used in FISH experiments on great apes and on representatives of Old World monkeys, New World monkeys, and lemurs to delineate the chromosome 6 phylogeny in primates. The domestic cat was used as an outgroup. The analysis showed a high marker order conservation, with few rearrangements required to reconcile the hypothesized chromosome 6 organization in primate ancestor with marker arrangement in all the examined species. Contrary to this simple evolutionary scenario, however, the centromere was found to be located in three distinct regions, without any evidence of chromosomal rearrangement that would account for its movement. One of the two centromere repositioning events occurred in great apes ancestor. The centromere moved from 6p22.1 to the present day location after the inversion event that differentiated marker order of the primate ancestor from the ancestor of Catarrhini. A cluster of intrachromosomal segmental duplications was found at 6p22.1, scattered in a region of about 9 Mb, which we interpret as remains of duplicons that flanked the ancestral centromere. Our data, therefore, suggest that some duplicon clusters found in noncentromeric/nontelomeric locations may represent traces of evolutionary silenced centromeres that inactivated after the occurrence of a centromere repositioning. In addition, the neocentromere emergence we have documented in Old World monkeys at 6q24.3 appears to have arisen and progressed without affecting the displaced flanking sequences.
Roles of sex hormones on bone morphogenetic protein signaling in pulmonary artery differed between testosterone and estrogen
Authors: Hiroaki Ichimori, Shigetoyo Kogaki, Kunihiko Takahashi, Keiichi Ozono
Journal: European Respiratory Journal (2011)

Background:  Epidemiologic studies have revealed the female predominance in the morbidity of idiopathic PAH (pulmonary arterial hypertension) in the world, suggesting involvement of sex hormones in the pathogenesis of PAH. Recent studies have identified a role of bone morphogenetic protein (BMP) signaling in the pathogenesis of PAH and we reported that BMP signaling in pulmonary arterial endothelial cells (PAEC) was attenuated under hypoxic condition  in vitro  and  in vivo .   Purpose:  The aim is to investigate effects of estradiol (E) and testosterone (T) on the BMP signaling in PAEC and analyze their mechanisms.   Materials and methods:  PAEC were cultured and incubated with β-estradiol (10 -7 M), testosterone (10 -8 M), or vehicle under 1%O 2  (hypoxia) and 21%O 2  (normoxia). BMP signaling including Smad1/5/8, phosphorylated (p-) Smad1/5/8, and Id1 was examined by western blotting and quantitative RT-PCR. The effects of HIF (hypoxia-inducible factor) -1α expression on the BMP signaling were also examined.   Results:  Under normoxia, p-Smad1/5/8 protein and Id1 mRNA were augmented 1.6 and 1.5-fold by E, but suppressed 0.3 and 0.4 -fold by T. Under hypoxia, conversely, p-Smad1/5/8 protein and Id1 mRNA were suppressed 0.5 and 0.4-fold by E, but augmented 3.2 and 2.4 -fold by T. HIF-1α accumulation led to alterlation of BMP signaling similar to hypoxia, whereas HIF-1α inhibitor altered the signaling similar to normoxia.   Discussion:  Sex hormones could change BMP signaling in PAEC depending on oxygen concentration. Our observations provide the new mechanism how sex hormone affects on BMP signaling, and sex hormones may be novel therapeutic targets in the treatment of PAH.
Antimetastatic Activity of a Preventive Cancer Vaccine
Authors: Patrizia Nanni, Giordano Nicoletti, Arianna Palladini, Stefania Croci, Annalisa Murgo, Agnese Antognoli, Lorena Landuzzi, Marina Fabbi, Silvano Ferrini, Piero Musiani, Manuela Iezzi, Carla De Giovanni, Pier-Luigi Lollini
Journal: Cancer Research (2007)

The development of prophylactic cancer vaccines that protect healthy hosts from tumor development leaves open the question whether such vaccines are also effective against established tumors and metastases. We tested the therapeutic activity of a proven prophylactic anti-HER-2/neu vaccine against successive stages of mammary carcinoma progression in HER-2/neu transgenic mice. The vaccine consisted of transgenic mammary carcinoma cells expressing HER-2/neu and two adjuvants: allogeneic class I histocompatibility antigens and interleukin (IL)-12. Vaccination of mice bearing lung micrometastases resulted in a 90% inhibition of metastasis development, whereas vaccination of mice with incipient local tumors was ineffective. The antimetastatic response was hampered by immune tolerance, as the protection of transgenic mice was lower than that of wild-type congenics not tolerant to HER-2/neu. A significant gain in immunotherapeutic activity in transgenic mice was obtained through the coadministration of anti-CD25 monoclonal antibody targeting regulatory T cells, which resulted in a >99% inhibition of metastasis. The immune responses elicited in transgenic mice comprised the activation of lung granulocytes and macrophages and of systemic adaptive responses based on helper T cells and their cytokines (IFN-gamma and IL-4) and anti-HER-2/neu antibodies. Dissection of relevant antimetastatic mechanisms by means of knockout mice and of depleting antibodies revealed a major difference between tumor prevention, which was completely dependent on anti-HER-2/neu antibodies, and metastasis therapy, which was antibody independent. In conclusion, a vaccine successfully developed for cancer immunoprevention showed a strong therapeutic activity against lung metastases mediated by protective immune mechanisms distinct from those preventing the onset of primary mammary carcinoma.
Seizure outcome after radiotherapy and chemotherapy in low-grade glioma patients: a systematic review
Authors: Johan A. F. Koekkoek, Melissa Kerkhof, Linda Dirven, Jan J. Heimans, Jaap C. Reijneveld, Martin J. B. Taphoorn
Journal: Neuro-Oncology (2015)

There is growing evidence that antitumor treatment contributes to better seizure control in low-grade glioma patients. We performed a systematic review of the current literature on seizure outcome after radiotherapy and chemotherapy and evaluated the association between seizure outcome and radiological response. Twenty-four studies were available, of which 10 described seizure outcome after radiotherapy and 14 after chemotherapy. All studies demonstrated improvements in seizure outcome after antitumor treatment. Eight studies reporting on imaging response in relation to seizure outcome showed a seizure reduction in a substantial part of patients with stable disease on MRI. Seizure reduction may therefore be the only noticeable effect of antitumor treatment. Our findings demonstrate the clinical relevance of monitoring seizure outcome after radiotherapy and chemotherapy, as well as the potential role of seizure reduction as a complementary marker of tumor response in low-grade glioma patients.
The conformational changes of the endoplasmic reticulum-mitochondria unit is involved in the pathogenesis of bronchial asthma
Authors: Yong Chul Lee, So Ri Kim, Dong Im Kim, Kyung Bae Lee
Journal: European Respiratory Journal (2014)

Under stress conditions, Endoplasmic reticulum (ER) loses the homeostasis in its functions, which is defined as ER stress. ER stress has been suggested to be involved in the inflammatory component of chronic diseases including bronchial asthma. The NLRP3 inflammasome is a molecular platform activated upon signs of cellular 9danger9 to trigger innate immune defenses through the maturation of pro-inflammatory cytokines such as IL-1b. Moreover, association between NLRP3 and mitochondria comes from the observation that activated NLRP3 appears to traffic from the ER to perinuclear areas similarly to mitochondria-associated ER membranes (MAMs). In this study, we aimed to investigate whether the allergen-induced cellular stress evokes the conformational association between ER and mitochondria in the airway inflammatory cells and which are involved in the pathogenesis of bronchial asthma. The mice sensitized with OVA and LPS and then challenged with OVA (OVA LPS -OVA mice) mice showed the typical features of neutrophilic asthma. Interestingly, confocal analysis and electron-microscopic findings revealed that in BAL cells from OVA LPS -OVA mice, the ER and mitochondria get closed each other even seemed to be united one compared to the finding of cells from control mice. An ER stress inhibitor significantly reduced the features of bronchial asthma and the conformational changes of organelles. These findings indicate that the development of ER-mitochondria complex induced by ER stress in airway inflammatory cells may be implicated in the pathogenesis of bronchial asthma, providing the novel therapeutic target for bronchial asthma.
Functional and antigenic properties of complement receptor type 2, CR2.
Authors: K Mitomo, T Fujita, K Iida
Journal: The Journal of Experimental Medicine (1987)

This is the first report demonstrating that C3d receptor (CR2) has functional activity in regulating complement cascade. Purified CR2 was examined for its cofactor activity in factor I-mediated cleavage of membrane-bound iC3b. CR2 plus C3b inactivator (I) released C3c from EA 125I-iC3b, and the release was inhibited when CR2 was preincubated with OKB7 monoclonal anti-CR2. Furthermore, immunoelectroblotting analysis showed crossreactivity of CR2 with 57H anti-CR1. These results indicate that CR2 has functional and antigenic similarity to CR1, thus providing a supporting evidence for placement of CR2 as a member of the recently defined gene family of C3- and C4-regulatory proteins composed of CR1, C4-binding protein, and factor H.
Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease
Authors: Melody A. Cobleigh, Charles L. Vogel, Debu Tripathy, Nicholas J. Robert, Susy Scholl, Louis Fehrenbacher, Janet M. Wolter, Virginia Paton, Steven Shak, Gracie Lieberman, Dennis J. Slamon
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Overexpression of the HER2 protein occurs in 25% to 30% of human breast cancers and leads to a particularly aggressive form of the disease. Efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody as a single agent was evaluated in women with HER2-overexpressing metastatic breast cancer that had progressed after chemotherapy for metastatic disease. PATIENTS AND METHODS: Two hundred twenty-two women, with HER2-overexpressing metastatic breast cancer that had progressed after one or two chemotherapy regimens, were enrolled. Patients received a loading dose of 4 mg/kg intravenously, followed by a 2-mg/kg maintenance dose at weekly intervals. RESULTS: Study patients had advanced metastatic disease and had received extensive prior therapy. A blinded, independent response evaluation committee identified eight complete and 26 partial responses, for an objective response rate of 15% in the intent-to-treat population (95% confidence interval, 11% to 21%). The median duration of response was 9.1 months; the median duration of survival was 13 months. The most common adverse events, which occurred in approximately 40% of patients, were infusion-associated fever and/or chills that usually occurred only during the first infusion, and were of mild to moderate severity. These symptoms were treated successfully with acetaminophen and/or diphenhydramine. The most clinically significant adverse event was cardiac dysfunction, which occurred in 4.7% of patients. Only 1% of patients discontinued the study because of treatment-related adverse events. CONCLUSION: Recombinant humanized anti-HER2 monoclonal antibody, administered as a single agent, produces durable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. Side effects that are commonly observed with chemotherapy, such as alopecia, mucositis, and neutropenia, are rarely seen.
Correction of platelet defect after splenectomy in hairy cell leukemia
Authors: D. L. Sweet
Journal: JAMA (1979)

ABSTRACT To the Editor.— Feiner et al (240:238, 1978) recently reported the loss of platelet aggregation dysfunction after splenectomy in a patient with hairy cell leukemia and thrombocytopenia. We have studied 11 patients with hairy cell leukemia, in whom the platelet counts were sufficiently high for platelet aggregation studies. Six patients demonstrated notable reduction of platelet aggregation with epinephrine. Three of these patients eventually had a splenectomy. Postsplenectomy aggregation curves stimulated by epinephrine, adenosine diphosphate, and collagen were normal.The pertinent clinical features of three patients with hairy cell leukemia in whom platelet aggregation study values returned to normal are shown in the Table. None of these patients complained of bruising easily or demonstrated petechiae, purpura, or ecchymoses. All of the patients denied recent aspirin or other drug exposure. All three patients demonstrated splenomegaly. In each case the diagnosis of hairy cell leukemia was confirmed by the observation of tartrate-resistant acid
Development of the Pacemaker Tissues of the Heart
Authors: Vincent M. Christoffels, Gertien J. Smits, Andreas Kispert, Antoon F. M. Moorman
Journal: Circulation Research (2010)

Pacemaker and conduction system myocytes play crucial roles in initiating and regulating the contraction of the cardiac chambers. Genetic defects, acquired diseases, and aging cause dysfunction of the pacemaker and conduction tissues, emphasizing the clinical necessity to understand the molecular and cellular mechanisms of their development and homeostasis. Although all cardiac myocytes of the developing heart initially possess pacemaker properties, the majority differentiates into working myocardium. Only small populations of embryonic myocytes will form the sinus node and the atrioventricular node and bundle. Recent efforts have revealed that the development of these nodal regions is achieved by highly localized suppression of working muscle differentiation, and have identified transcriptional repressors that mediate this process. This review will summarize and reflect new experimental findings on the cellular origin and the molecular control of differentiation and morphogenesis of the pacemaker tissues of the heart. It will also shed light on the etiology of inborn and acquired errors of nodal tissues.