tbuckley/cabot-search huggingface dataset:
Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma
Authors: Richard F. Little, Karen Aleman, Pallavi Kumar, Kathleen M. Wyvill, James M. Pluda, Elizabeth Read-Connole, Victoria Wang, Stefania Pittaluga, Andrew T. Catanzaro, Seth M. Steinberg, Robert Yarchoan
Journal: Blood (2007)
Cell surface antigens of human malignant melanoma. II. Serological typing with immune adherence assays and definition of two new surface antigens.
Authors: H Shiku, T Takahashi, H F Oettgen
Journal: The Journal of Experimental Medicine (1976)

Immune adherence assays revealed that 10 out of 18 melanoma patients had demonstrable antibody to surface antigens of autologous cultured melanoma cells, with serum titers ranging from 1/4 to 1/160. Autologous fibroblasts showed no reactions with these sera. Antibody from individual patients showed reproducible temperature preference for maximal reactivity. Two new melanoma antigenic systems were defined in this study. The first, BD, was restricted to autologous melanoma and could not be demonstrated in absorption tests on 12 allogeneic melanoma cell lines. The other, AH, was found on 5 of 12 melanomas and represents a class of shared melanoma surface antigens. Neither BD nor AH antigen was found on normal cells from autologous, allogeneic, or xenogeneic sources or on any nonmelanoma tumor cell line. Methods are now available to develop a comprehensive serological classification of the surface antigens of melanoma.
Human interleukin 1. Purification to homogeneity.
Authors: S R Kronheim, C J March, S K Erb, P J Conlon, D Y Mochizuki, T P Hopp
Journal: The Journal of Experimental Medicine (1985)

We have purified human interleukin 1 (IL-1) to homogeneity by a simplified procedure that results in excellent yields of pure material that retains a high level of biological activity. IL-1, secreted by human peripheral blood macrophages that have been stimulated with Staphylococcus aureus, was purified by ion exchange chromatography and affinity chromatography on Procion Red agarose. The pure protein has a specific activity of 3.2 X 10(8) U/mg in the thymocyte mitogenesis assay, and is pyrogenic. No molecular weight heterogeneity was observed, in contrast to findings for mouse IL-1 and earlier reports of human IL-1. Purified IL-1, as analyzed by two-dimensional electrophoresis/electrofocusing gels, exhibited a series of charged species with isoelectric points ranging from 6.0 to 4.9, all with a molecular weight of approximately 17,500. Amino acid analysis indicated an abundance of acidic residues, in agreement with the low isoelectric points. There is little or no cysteine in the molecule. No evidence was found for the presence of carbohydrate moieties. The overall yield for this procedure was approximately 31% of the activity contained in the initial culture supernatant.
Overexpression of TLR7 promotes cell-intrinsic expansion and autoantibody production by transitional T1 B cells
Authors: Natalia V. Giltiay, Craig P. Chappell, Xizhang Sun, Nikita Kolhatkar, Thomas H. Teal, Alice E. Wiedeman, Jinoh Kim, Lena Tanaka, Matthew B. Buechler, Jessica A. Hamerman, Thereza Imanishi-Kari, Edward A. Clark, Keith B. Elkon
Journal: The Journal of Experimental Medicine (2013)

Toll-like receptor (TLR), a ligand for single-stranded RNA, has been implicated in the development of pathogenic anti-RNA autoantibodies both in systemic lupus erythematous (SLE) patients and in murine models of lupus. It is still unclear, however, where and how TLR7-mediated interactions affect the development of autoreactive B cells. We found that overexpression of TLR7 in transgenic mice (TLR7.1Tg) leads to marked alterations of transitional (T1) B cells, associated with their expansion and proliferation within the splenic red pulp (RP). This phenotype was intrinsic to the T1 subset of B cells and occurred independently of type 1 IFN signals. Overexpression of RNase in TLR7.1Tg mice significantly limited the expansion and proliferation of T1 cells, indicating that endogenous RNA complexes are driving their activation. TLR7.1Tg T1 cells were hyper-responsive to anti-IgM and TLR7 ligand stimulation in vitro and produced high concentrations of class-switched IgG2b and IgG2c, including anti-RNA antibodies. Our results demonstrate that initial TLR7 stimulation of B cells occurs at the T1 stage of differentiation in the splenic RP and suggest that dysregulation of TLR7 expression in T1 cells can result in production of autoantibodies.
A New Method for Quantitation of Tumor Growth In Situ: Measurement by Plethysmography2
Authors: Calbert A. Laing, Don E. Griswold, Gloria H. Heppner
Journal: JNCI Journal of the National Cancer Institute (1973)

Plethysmography (volumetric measurement by fluid displacement) was used to quantitate changes in tumor volume, in situ, with the mouse mammary tumor as a model system. The technique relied on the ability to propagate tumors subplantarly in susceptible mouse strains. Such tumors retained the histologic features of the original mouse mammary adenocarcinoma and could be serially propagated subplantarly, subcutaneously, and intradermally. The method is precise and convenient for assessingchanges in tumor volume without altering the relationship between the tumor and its host.
Testing for “Snowballing” Hybrid Incompatibilities in Solanum: Impact of Ancestral Polymorphism and Divergence Estimates
Authors: Thomas Städler, Ana Marcela Florez-Rueda, Margot Paris
Journal: Molecular Biology and Evolution (2011)

Two recent high-profile studies offered empirical evidence for a “snowballing” accumulation of postzygotic incompatibilities in Drosophila and Solanum (tomatoes). Here we present a reanalysis of the Solanum data that is motivated by population genetic principles. Specifically, the high levels of intraspecific nucleotide polymorphism in wild tomato species and presumably large effective population size throughout the divergence history of this clade imply that ancestral polymorphism should be taken into account when evaluating sequence divergence between species. Based on our reanalyses of synonymous-site divergence between the four focal Solanum species and a wide range of ancestral polymorphism, we assessed under which conditions the reported accumulation of seed sterility factors supports the snowball effect. Our results highlight the pivotal impact of levels of ancestral polymorphism and alternate divergence values, and they illustrate that robust tests of the snowball effect in Solanum require genome-wide estimates of divergence.
Two cases of hypothalamic-pituitary sarcoidosis
Authors: D Smith, M J Cullen
Journal: Journal of the Royal Society of Medicine (2005)

shortness of breath and abdominal distension the methotrexate was immediately stopped.On examination he had gross ascites.Constrictive pericarditis secondary to rheumatoid arthritis was excluded by cardiac MRI.Diagnostic peritoneal tap revealed an exudate and so the possibility of peritoneal disease was further investigated by laparoscopy, at which peritoneal and liver biopsies were obtained.The liver biopsy was normal but the peritoneal biopsy showed a fibrinous peritonitis with a mild chronic inflammatory infiltrate (Figure 1) similar to that seen in fibrinous pericarditis associated with rheumatoid arthritis.Repeated drainage of the ascites was necessary after the patient's discharge from hospital, but after institution of prednisolone 15 mg daily there was no recurrence.The methotrexate was not reintroduced because the rheumatoid arthritis was well controlled. COMMENTAn extensive search of the published work has yielded two reported cases of ascites related to rheumatoid arthritis. 1,2n these instances the aetiology was judged to be methotrexate-induced liver damage and the ascites resolved on withdrawal of the drug.4][5][6] The fibrinous peritonitis in this patient was histologically very reminiscent of the constrictive pericarditis seen in rheumatological arthritis.
Tumors of the Pediatric Central Nervous System
Authors: C. van den Bos
Journal: Annals of Oncology (2002)

This recently published book provides a generally good overview of the field of paediatric neuro-oncology. It is beautifully illustrated and for quick reference all chapters display the most relevant information in well placed, orderly numbered boxes. The four sections (Current Diagnosis and Therapeutic Approaches; Intracranial Tumours; Spinal Cord Tumours; Outcomes and Complications) cover all aspects of the care of children with central nervous system (CNS) tumours. About one third of the first section is covered by the chapter on surgical neuropathology. Considerably smaller is the chapter on the anaesthetic considerations of CNS tumours and which does not cover all of the aspects of anaesthesia in these patients. As with the chapter on anaesthesia, the other chapters in this section provide adequate information for paediatric oncologists and neurosurgeons to enable them to confer initial information on these aspects to the patient and parents. But they do not provide all the necessary information required by, for example, anesthetists, intensivists and radiotherapists. In the second part of the book, intracranial tumors are discussed in separate, readable chapters. Not all of the information on ongoing clinical trials is exactly up to date, which is understandable. However, more information about these trials is provided in the last section. Treatment proposals based solely on these chapters might not cover all the possible beneficial treatment modalities. However, since care for paediatric neuro-oncology patients is in general provided by multidisciplinary teams, the danger of not considering all of the treatment modalities is small. The third part of the book, which discusses spinal cord tumours, is more or less an extension of the second part. A chapter in this section also covers peripheral nerve tumours, strictly speaking not tumours of the CNS. In the last section, the chapter on Cooperative Group Trials gives the reader a nice overview of current treatment regimens provided by the different groups. Explanations of the different types of study (phase I, II and III) appears a bit superfluous for the target readership of this book. A major negative point of the book is the rather short chapter on the late effects in long-term survivors. Of all childhood cancer survivors, those that are recovering from brain tumours generally suffer the most from treatment sequelae. This chapter does not give any clear guidelines for the follow-up of CNS-tumour survivors. A general scheme for short- and long-term follow-up would have been very welcome. Nevertheless, this book provides the reader with readily accessible up-to-date information in the complex field of CNS tumours. It will therefore be especially useful to young medical staff members in paediatric oncology and neurosurgery departments; as such, it is almost a must for training hospitals. However, all those interested in the treatment of children with CNS tumours are also likely to find it useful and certainly worth the money.
A multicentre observational study of presentation and early assessment of acute stroke
Authors: F. Harraf
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective</b>:To investigate delays in the presentation to hospital and evaluation of patients with suspected stroke. <b>Design</b>: Multicentre prospective observational study. <b>Setting</b>: 22 hospitals in the United Kingdom and Dublin. <b>Participants</b>: 739 patients with suspected stroke presenting to hospital. <b>Main outcome measures</b>: Time from onset of stroke symptoms to arrival at hospital, and time from arrival to evaluation by a senior doctor. <b>Results</b>: The median age of patients was 75 years, and 400 were women. The median delay between onset of symptoms and arrival at hospital was 6 hours (interquartile range 1 hour 48minutes to 19 hours 12 minutes). 37% of patients arrived within 3 hours, 50% within 6 hours. The median delay for patients using the emergency service was 2 hours 3 minutes (47 minutes to 7 hours 12 minutes) compared with 7 hours 12 minutes (2 hours 5 minutes to 20 hours 37 minutes) for referrals from general practitioners (P&lt;0.0001). Use of emergency services reduced delays to hospital (odds ratio 0.45, 95% confidence interval 0.23 to 0.61). The median time to evaluation by a senior doctor was 1 hour 9 minutes (interquartile range 33 minutes to 1 hour 50 minutes) but was undertaken in only 477 (65%) patients within 3 hours of arrival. This was not influenced by age, sex, time of presentation, mode of referral, hospital type, or the presence of a stroke unit. Computed tomography was requested within 3 hours of arrival in 166 (22%) patients but undertaken in only 60 (8%). <b>Conclusion</b>: Delays in patients arriving at hospital with suspected stroke can be reduced by the increased use of emergency services. Over a third of patients arrive at hospital within three hours of stroke; their management can be improved by expediting medical evaluation and performing computed tomography early.
In-hospital vs Out-of-hospital presentation of life-threatening ventricular arrhythmia predicts survival - results from the Antiarrhythmics vs Implantable Defibrillators (AVID) registry
Authors: A.E. Epstein, E.Graham Renfroe, J. Powell, C.H. Kim, C. Ocampo, D.S. Cannom, J.M. Herre, P.L. Friedman, Q. Yao, S. Lancaster, Y. Rosenberg
Journal: Journal of the American College of Cardiology (1998)
Functional and Structural Assessment of Intercellular Communication
Authors: Bruce J. Darrow, Vladimir G. Fast, André G. Kléber, Eric C. Beyer, Jeffrey E. Saffitz
Journal: Circulation Research (1996)

Remodeling of conduction pathways in the hypertrophic response to myocardial injury is a potential mechanism leading to the development of anatomic substrates of lethal arrhythmias. To delineate the responsible mechanisms and to directly relate changes in intercellular coupling at gap junctions with electrophysiological alterations, we studied the effects of cAMP, a mediator of cardiac hypertrophy, on action potential conduction velocity and connexin expression in neonatal rat ventricular myocyte cultures. Conduction velocity was measured with an optical activation mapping technique in cells loaded with the voltage-sensitive dye RH-237. Action potentials were conducted 24% to 29% more rapidly (P < .005) after incubating cultures for 24 hours with the cAMP analogue dibutyryl cAMP (db-cAMP, 1 mmol/L). However, db-cAMP caused no change in the maximum rate of rise of the action potential upstroke, Vmax. Electron and immunofluorescence microscopy revealed a significant increase in the number and size of gap junctions in db-cAMP-treated cells. Immunoblotting showed that the total amounts of the ventricular gap junction proteins connexin43 and connexin45 (Cx43 and Cx45, respectively) increased 2- to 4-fold. Immuno-precipitation of metabolically labeled connexin proteins revealed a dose-dependent increase in the rate of Cx45 protein synthesis in myocytes exposed to db-cAMP ( > 2-fold after a 4-hour exposure) but no change in the Cx43 synthesis rate. Northern blot analysis demonstrated a time-dependent increase in the amount of Cx43 mRNA, with a maximum 3.3-fold increase after 4 hours of exposure to 1 mmol/L db-cAMP; cycloheximide did not block this effect. In contrast, Cx45 mRNA levels were not altered significantly after db-cAMP treatment. Thus, cAMP causes a significant increase in conduction velocity that appears to be attributable largely to enhanced expression of proteins responsible for intercellular communication. Cx43 and Cx45 levels appear to be upregulated by cAMP by disparate molecular mechanisms.
Proton pump inhibitor-therapy refractory gastro-oesophageal reflux disease patients, who are they?
Authors: A. J Bredenoord, J. Dent
Journal: Gut (2007)

In a recent version of Gut , Mainie and colleagues report on patients with persistent symptoms despite acid suppressive therapy.1 This is often presented as a considerable problem and impedance seems useful in the evaluation of these patients. The importance of the phenomenon of proton pump inhibitor(PPI)-refractory symptoms is also stressed in studies in which the need for a new anti-reflux drug is propagated. However, we think some caution is appropriate when speaking of PPI-refractory gastro-oesophageal reflux disease …
Albuminuria and Cardiovascular Risk in Hypertensive Patients with Left Ventricular Hypertrophy: The LIFE Study
Authors: Kristian Wachtell
Journal: Annals of Internal Medicine (2003)

Background: Several studies have shown that albuminuria is associated with increased risk for fatal and nonfatal cardiovascular events, independent of conventional risk factors. The partition values for urine albumin–creatinine ratio (UACR) used to identify microalbuminuria have been based on studies that predicted risk in diabetic patients. Objective: To determine whether the relation between albuminuria and cardiovascular risk can be used to predict cardiovascular morbidity and mortality in hypertensive patients. Design: Multicenter cohort study derived from a randomized, controlled trial. Patients: 8206 patients with stage II or III hypertension randomly assigned to double-blind therapy with losartan or atenolol. Follow-up was 39 122 patient-years. Measurements: Renal glomerular permeability evaluated by UACR. Results: In nondiabetic hypertensive patients with left ventricular hypertrophy, the risk for the composite cardiovascular end point increased continuously as albuminuria increased (P < 0.001 for trend). There was no specific threshold for increased risk. For every 10-fold increase in UACR, hazard ratios in nondiabetic patients increased as follows: composite end point, by 57% (95% CI, 40.6% to 75.0%); cardiovascular mortality, by 97.7% (CI, 66.5% to 235%); all-cause mortality, by 75.2% (CI, 54.0% to 99.4%); stroke, by 51.0% (CI, 28.8% to 76.9%); and myocardial infarction, by 45% (CI, 19.9% to 75.4%) (P < 0.001 for all comparisons). Values were similar in diabetic patients, although for myocardial infarction the trend was weaker and not significant. Conclusion: Increased UACR resulted in increasing risk for cardiovascular morbidity and mortality among hypertensive patients with left ventricular hypertrophy. We found no thresholds or plateaus. Risk increases at much lower UACR values than has been reported among diabetic patients.
Differential Methylation Status of Tumor-Associated Genes in Head and Neck Squamous Carcinoma
Authors: Shin-ichiro Maruya, Jean-Pierre J. Issa, Randal S. Weber, David I. Rosenthal, Joie C. Haviland, Reuben Lotan, Adel K. El-Naggar
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Promoter hypermethylation is one of the major mechanisms in the transcriptional inactivation of certain carcinoma-associated genes. Concurrent methylation analysis of multiple, functionally distinct genes may provide important information on their differential alterations and potential association in head and neck squamous carcinogenesis. Experimental Design: Methylation-specific PCR analysis of the CpG islands of 8 cancer-related genes was performed on 19 cell lines and 32 primary head and neck squamous cell carcinoma (HNSC) specimens with matched histologically normal mucosa and 6 dysplastic lesions. The methylation status and histological features of the specimens were investigated. Results: In histologically normal squamous mucosa, no to low-level methylation (0–22%) was noted in some specimens at all genes except RARβ2 (50%). Considerable variation in the incidence of methylation of these genes within and between cell lines and tumor specimens was noted. The highest incidences of methylation in the cell lines and primary tumors were noted in RARβ2 (53%), MGMT (37%), p16 (33%), and DAP-K (25%); low incidence of methylations were noted in E-cadherin (2%), p73 (2%) RASSF1A (10%), and p14 (20%) genes. The incidences of methylation of each gene were almost similar between the HNSC cell lines and primary cancer specimens, although methylation of RASSF1A was observed in cell line (26%), but not in dysplasia and primary tumor. RARβ, p16, and MGMT genes showed the highest incidences of methylation in premalignant and invasive carcinomas. Conclusions: Methylation of p16, RARβ, and MGMT may constitute early events in HNSC tumorigenesis. The infrequent methylation at certain genes suggests a minimal role for this feature in their functional assessment in HNSC. The variability within and between cell lines and tumor specimens supports a heterogeneous and dynamic state of methylation in genes associated with HNSC tumorigenesis.
Advances in patient education in rheumatic disease.
Authors: L H Daltroy, M H Liang
Journal: Annals of the Rheumatic Diseases (1991)

Education of patients with arthritis began with an emphasis on conveying knowledge, grew to include behaviour change, compliance, and more general coping and management of disease and then progressed to consider physical and psychosocial health outcomes. Research continues in all these areas. Control, in many forms (locus of control, self perceived efficacy, learned helplessness), is now suggested to be a central mediating variable. Evaluation of programmes is moving away from programme v usual care towards comparison of alternative methods of delivery and matching of method to learner. The first generation of researchers in arthritis education tended to be care givers with little formal education in behavioural sciences and evaluation methodology; the programmes they designed were often empirically based. The current generation, nurtured in large part by funds from the Arthritis Foundation and the National Institutes of Health, is better trained in designing programmes grounded in behavioural sciences and educational theory. In the long run, collaborations with care givers and patients will considerably strengthen the effectiveness of education programmes for patients. A variety of educational strategies have been shown to change the knowledge, behaviour, and health of patients with arthritis for the better. Many methods seem to work, so long as the programme is planned, has a goal, and is accountable. There is much work still to be done to teach care givers to be better teachers, and patients to be better managers of their diseases, in concert with their doctors, and to focus on high risk groups. Although most work has been done with patients with rheumatoid arthritis and osteoarthritis, many of these findings can and should be safely generalised to less studied rheumatic diseases. Finally, we need to consider the patient first as a person, and to provide education through all avenues, not just the medical care system.
Retinoic acid induces alveolar regeneration in the adult mouse lung
Authors: M. Hind, M. Maden
Journal: European Respiratory Journal (2004)

Recent data suggests that exogenous retinoic acid (RA) can induce alveolar regeneration in a mouse and a rat model of experimental emphysema and disrupted alveolar development. This may be because RA is required during normal alveolar development and the subsequent provision of RA reawakens the gene cascades used during development. Here, additional evidence that RA is required during alveologenesis in the mouse is provided by showing that disulphiram disrupts this process. A further model of disrupted alveolar development using dexamethasone administered postnatally is then described, and it is further shown that RA administered to these adult mice restores the lung architecture to normal. Alveolar regeneration with retinoic acid may therefore be an important novel therapeutic approach to the treatment of respiratory diseases characterised by a reduced gas-exchanging surface area, such as bronchopulmonary dysplasia and emphysema.