tbuckley/cabot-search huggingface dataset:
Optimizing a Novel Regional Chemotherapeutic Agent against Melanoma: Hyperthermia-Induced Enhancement of Temozolomide Cytotoxicity
Authors: Sae Hee Ko, Tomio Ueno, Yasunori Yoshimoto, Jin Soo Yoo, Omar I. Abdel-Wahab, Zeinab Abdel-Wahab, Edward Chu, Scott K. Pruitt, Henry S. Friedman, Mark W. Dewhirst, Douglas S. Tyler
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Previous preclinical studies have shown that regional temozolomide therapy via isolated limb infusion is more effective than melphalan, the current drug of choice for regional chemotherapy for advanced extremity melanoma. The aim of this study was to determine whether hyperthermia could further augment the efficacy of temozolomide, an alkylating agent, against melanoma and improve its therapeutic index in a rat model of isolated limb infusion. Experimental Design: Athymic rats bearing s.c. human melanoma xenografts (DM6) in their hind limbs were randomized to a 15-minute isolated limb infusion procedure with or without temozolomide at room temperature, normothermic (37.5°C), or hyperthermic (43°C) conditions. Results: The concomitant administration of hyperthermia during an infusion with temozolomide led to the greatest increase in tumor growth delay, decreased proliferative index, and increased cell death. Isolated limb infusion treatment with a low dose (350 mg/kg) of temozolomide was ineffective at producing tumor growth delay (P = 0.07). Similarly, temozolomide infusion under normothermia yielded minimal tumor growth delay (P = 0.08). In contrast, the combination of hyperthermia plus temozolomide treatment produced marked tumor growth delay of 10.4 days (P = 0.02) with minimal toxicity. The addition of heat to temozolomide treatment yielded the smallest proliferative index (P = 0.001), while markedly increasing the level of apoptosis 48 hours after isolated limb infusion. Conclusion: This study, the first to examine the interaction between hyperthermia and temozolomide, shows a strong, synergistic antitumor effect when hyperthermia is combined with temozolomide for regional treatment of melanoma confined to an extremity. The mechanism of this synergy seems to be through an augmentation, by hyperthermia, of the antiproliferative and proapoptotic effects of temozolomide.
Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, and FCU
Authors: Bénédicte Neven, Isabelle Callebaut, Anne-Marie Prieur, Jérôme Feldmann, Christine Bodemer, Loredana Lepore, Beata Derfalvi, Suata Benjaponpitak, Richard Vesely, Marie-Jose Sauvain, Stefan Oertle, Roger Allen, Gareth Morgan, Arndt Borkhardt, Clare Hill, Janet Gardner-Medwin, Alain Fischer, Geneviève-De Saint-Basile
Journal: Blood (2003)
Blockade of Hedgehog Signaling Inhibits Pancreatic Cancer Invasion and Metastases: A New Paradigm for Combination Therapy in Solid Cancers
Authors: Georg Feldmann, Surajit Dhara, Volker Fendrich, Djahida Bedja, Robert Beaty, Michael Mullendore, Collins Karikari, Hector Alvarez, Christine Iacobuzio-Donahue, Antonio Jimeno, Kathleen L. Gabrielson, William Matsui, Anirban Maitra
Journal: Cancer Research (2007)

In the context of pancreatic cancer, metastasis remains the most critical determinant of resectability, and hence survival. The objective of this study was to determine whether Hedgehog (Hh) signaling plays a role in pancreatic cancer invasion and metastasis because this is likely to have profound clinical implications. In pancreatic cancer cell lines, Hh inhibition with cyclopamine resulted in down-regulation of snail and up-regulation of E-cadherin, consistent with inhibition of epithelial-to-mesenchymal transition, and was mirrored by a striking reduction of in vitro invasive capacity (P < 0.0001). Conversely, Gli1 overexpression in immortalized human pancreatic ductal epithelial cells led to a markedly invasive phenotype (P < 0.0001) and near total down-regulation of E-cadherin. In an orthotopic xenograft model, cyclopamine profoundly inhibited metastatic spread; only one of seven cyclopamine-treated mice developed pulmonary micrometastases versus seven of seven mice with multiple macrometastases in control animals. Combination of gemcitabine and cyclopamine completely abrogated metastases while also significantly reducing the size of "primary" tumors. Gli1 levels were up-regulated in tissue samples of metastatic human pancreatic cancer samples compared with matched primary tumors. Aldehyde dehydrogenase (ALDH) overexpression is characteristic for both hematopoietic progenitors and leukemic stem cells; cyclopamine preferentially reduced "ALDH-high" cells by approximately 3-fold (P = 0.048). We confirm pharmacologic Hh pathway inhibition as a valid therapeutic strategy for pancreatic cancer and show for the first time its particular efficacy against metastatic spread. By targeting specific cellular subpopulations likely involved in tumor initiation at metastatic sites, Hh inhibitors may provide a new paradigm for therapy of disseminated malignancies, particularly when used in combination with conventional antimetabolites that reduce "bulk" tumor size.
Some Remarks upon Remedies, and on the Study of their Actions
Authors: C. H. Jones
Journal: BMJ (1862)

<h3>Abstract</h3> Trawling has been shown to cause high mortality of discarded species (bycatch) and short-term ecological disturbance to bottom communities in coastal systems, resulting in lowered benthic biomass. Here we report evidence of a trawling-induced trophic cascade resulting in an increase in biomass of benthic polychaetes after the end of the shrimp trawling season in areas open to trawling in North Carolina (USA). Using comparative measurements of abundance of bycatch species and benthos in open and closed trawling management areas and Ecopath network modeling, we show that trawling in the open area has led to increases in deposit-feeding polychaetes and decreases in bycatch species (fish and crabs) that are benthic predators on the polychaetes. We conclude that proposed management actions to reduce the shrimp trawl fishery effort will influence other net and trap fisheries for southern flounder and blue crabs indirectly, as revealed by our network models, and the proposed trawling ban may lead to improvements in other valuable fisheries.
Jacobsen Syndrome With Combined Variable Immunoddeficiency (CIVD)
Authors: Arnaldo C. Porto Neto, Julio Mella Pierezan, Joao Paulo Bordin, Julia Noschang, Juliana Gotardo, Juliana Moro, Jorge Luigi Orso, Jamile Pedroni, Jessica Zandona
Journal: Journal of Allergy and Clinical Immunology (2014)
T-lymphocyte-enriched murine peritoneal exudate cells. IV. Genetic control of cross-stimulation at the T-cell level.
Authors: R H Schwartz, C L Horton, W E Paul
Journal: The Journal of Experimental Medicine (1977)

Antibodies raised against many structurally related antigens have been shown to cross-react extensively. Manifestations of T-cell immunity, on the other hand, appear to be more restricted in their ability to be elicited by cross-reacting antigens, although examples have been reported. This paper explores the nature of the cross-reactions at the T-cell level among the branched-chain copolymers (T,G)-A--L, (phi,G)-A--L, (H,G)-A--L, and G-A--L, as well as a related linear terpolymer, GAT, in a variety of mouse strains using the peritoneal exudate T-lymphocyte-enriched cells (PETLES) proliferation assay. (T,G)-A--L, (phi,G)-A--L, and GAT could cross-stimulate cells immune to the other two antigens, whereas (H,G)-A--L, (T,G)-Pro--L, and G-A--L showed no cross-stimulations. The extent of the cross-reactions varied with the mouse strain and was shown to be under the control of immune response genes. It was necessary for the strain to be able to respond to both the immunogen and the cross-reacting antigen, when used as an immunogen, in order for cross-stimulation to occur; however, this was not always sufficient. Several examples of unequal or one-way cross-reactions were found. In addition, the immune responses to (H,G)-A--L and (phi,G)-A--L showed no cross-reactions with the other antigen even though their Ir genes were both mapped to the K region or I-A subregion. The problem of accounting for such fine specificity of T-cell recognition in lieu of the genetic evidence demonstrating only Ir gene control of the response is discussed.
Epidermal proliferation of nude mouse skin, pig skin, and pig skin grafts. Failure of nude mouse skin to respond to the tumor promoter 12-O-tetradecanoyl phorbol 13-acetate.
Authors: G G Krueger, D A Chambers, J Shelby
Journal: The Journal of Experimental Medicine (1980)

Human skin transplanted to nude mice offers a possible experimental system for the study of normal epidermal proliferation and differentiation, and for their pathological counterparts. Crucial to the development of such a system is the demonstration that such grafts retain the responsive features of donor skin. To document that donor proliferative characteristics are maintained in the grafts, a comparative analysis of agents that induce proliferation was made on skin of mice homozygous and heterozygous for nude, on pig skin, and on pig skin transplanted onto nude mice. A wave of epidermal proliferation could be induced in pig skin and pig skin grafted onto nude mice, but not in nude mouse skin after the topical application of 10 ng 12-O-tetradecanoyl phorbol 13-acetate (TPA). A 10-fold greater concentration of TPA or 5% croton oil induced proliferation in all species of epidermis studied. Mice, heterozygous for nude, showed a normal response to 10 ng TPA, suggesting that the ability to respond to TPA may be related, in part, to a recessive genetic trait. Nude mouse skin transplanted to a heterozygous littermate capable of responding to 10 ng TPA does not respond. These observations argue that: the graft retains its donor proliferative characteristics when transplanted to the nude, and the inability of the nude mouse to respond to lower doses of TPA may be related to absorption, the nude gene(s), or an inherent threshold to response. The lack of response to the promoter TPA provides a plausible explanation for the decreased incidence of tumors arising in nude mice during two-stage carcinogenesis experiments.
Rheumatoid arthritis and genetic markers in Syrian and French populations: different effect of the shared epitope
Authors: L. Kazkaz, H. Marotte, M. Hamwi, M. Angelique Cazalis, P. Roy, B. Mougin, P. Miossec
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To investigate whether ethnic differences exist in the effect of the shared epitope and selected cytokine gene polymorphisms on the susceptibility and severity of rheumatoid arthritis in Syria (Damascus) and France (Rhône-Alpes area). <b>Methods:</b> 156 patients with rheumatoid arthritis and 120 healthy controls from Syria were compared with 512 patients with rheumatoid arthritis and 471 healthy controls from France. Shared epitope status, cytokine gene polymorphisms interleukin (IL)-1B +3954, IL-1RN +2018 and tumour necrosis factor α promoter (−238 and −308) were analysed by enzyme-linked oligosorbent assay. Joint destruction was defined by a right wrist Larsen score ⩾2. Odds ratios (ORs) were calculated. <b>Results:</b> In both countries, a dose effect was observed between the shared epitope copy number and rheumatoid arthritis (Syria: OR 1 <i>v</i> 0 copies = 1.6, p = NS; OR 2 <i>v</i> 0 = 15.3, p&lt;0.01; and France: OR 1 <i>v</i> 0 = 2.3, p&lt;0.001; OR 2 <i>v</i> 0 = 7.2, p&lt;0.001). A dose effect was also observed between the shared epitope copy number and joint destruction in Syria (OR 1 <i>v</i> 0 = 2.2, p = NS; OR 2 <i>v</i> 0 = 9.9, p&lt;0.01) and France (OR 1 <i>v</i> 0 = 1.8, p&lt;0.01; OR 2 <i>v</i> 0 = 4.8, p = 0.001). The dose effect of the shared epitope was greater in Syria than in France. Only the −238 tumour necrosis factor α polymorphism was associated with joint destruction in the Syrian population (p&lt;0.05). However, after adjustment for age, sex, disease duration and rheumatoid factor for severity, this association disappeared. <b>Conclusion:</b> The frequency of the shared epitope was increased in the French population with rheumatoid arthritis and in controls, but the association between the shared epitope and joint destruction was more pronounced in the Syrian population, with an OR of almost 10 for the homozygotes.
Lysophosphatidic Acid Positively Regulates the Fluid Flow–Induced Local Ca <sup>2+</sup> Influx in Bovine Aortic Endothelial Cells
Authors: Hisayuki Ohata, Tadahiro Ikeuchi, Aya Kamada, Masayuki Yamamoto, Kazutaka Momose
Journal: Circulation Research (2001)

Abstract —Using real-time confocal microscopy, we have demonstrated that lysophosphatidic acid (LPA), a bioactive phospholipid existing in plasma, positively regulates fluid flow–induced [Ca 2+ ] i response in fluo 4–loaded, cultured, bovine aortic endothelial cells. The initial increase in [Ca 2+ ] i was localized to a circular area with a diameter of &lt;4 μm and spread concentrically, resulting in a mean global increase in [Ca 2+ ] i . The local increase often occurred in a stepwise manner or repetitively during constant flow. The percentage of cells that responded and the averaged level of increase in [Ca 2+ ] i were dependent on both the concentration of LPA (0.1 to 10 μmol/L) and the flow rate (25 to 250 mm/s). The response was inhibited by removing extracellular Ca 2+ or by the application of Gd 3+ , an inhibitor of mechanosensitive (MS) channels, but not by thapsigargin, an inhibitor of the endoplasmic reticular Ca 2+ -ATPase. It was also inhibited by 8-bromo-cGMP, and the inhibition was completely reversed by KT5823, an inhibitor of protein kinase G (PKG). These results suggest that the [Ca 2+ ] i response arises from Ca 2+ influx through Gd 3+ -sensitive MS channels, which are negatively regulated by the activation of PKG. The spatiotemporal properties of the [Ca 2+ ] i response were completely different from those of a Ca 2+ wave induced by ATP, a Ca 2+ -mobilizing agonist. Therefore, we called the phenomenon Ca 2+ spots. We conclude that LPA positively regulates fluid flow–induced local and oscillatory [Ca 2+ ] i increase, ie, the Ca 2+ spots, in endothelial cells via the activation of elementary Ca 2+ influx through PKG-regulating MS channels. This indicates an important role for LPA as an endogenous factor in fluid flow–induced endothelial function.
Atlas of Gastroenterology Self- Assessment Guide
Authors: R T PRZEMIOSLO
Journal: Gut (1997)

Atlas of Gastroenterology Self- Assessment Guide. Yamada T, Alpers DH, Owyany C, Powell DW, Sliverstein FE. (Pp 368; illustrated; £46.00.) Philadelphia: Lippincott-Raven Publishers, 1996. ISBN 0-397-51788-2.

Yet another picture book of self-assessment anecdotes I hear you groan! This new book contains 98 cases which illustrate a whole range of gastrointestinal and hepato-biliary diagnoses. Most of the cases presented consist of common clinical problems, such as coeliac sprue and colonic polyps, with the occasional addition of diagnoses only rarely encountered in a clinician’s lifetime. The book is written in self-assessment format and is aimed at students sitting board exams as well as seasoned physicians. Although only a small book, it is not portable as the excellent but …
Direct Health Care Costs of Diabetic Patients in Spain
Authors: Juan Oliva, Félix Lobo, Begoña Molina, Susana Monereo
Journal: Diabetes Care (2004)

OBJECTIVE—The goal of this study was to estimate the health care resources spent by type 1 and type 2 diabetic patients in Spain during the year 2002. RESEARCH DESIGN AND METHODS—This is a cost-of-illness study focusing on direct health care costs estimated from primary and secondary sources of information. A prevalence of diabetes ranging from 5 to 6% of the adult population was determined. Total cost is composed of six items: insulin and oral hypoglycemic agents, other drugs, disposable and consumable goods (glucose test strips, needles, and syringes), hospitalization, primary care visits, and visits to endocrinologists and dialysis. RESULTS—The estimated direct cost of diabetes in 2002 ranges from €2.4 to 2.67 billion. Hospital costs were the most (€933 million), followed by noninsulin, nonhypoglycemic agent drugs (€777–932 million). Much lower are the costs of insulin and oral hypoglycemic agents (€311 million), primary care visits (€181–272 million), specialized visits (€127–145 million), and disposable elements (€70–81 million). Expenditures for all drugs and consumable goods ranged between €1.16 and 1.3 billion, representing 48–49% of total cost, which is 15% higher than hospital costs. CONCLUSIONS—The direct health care costs of diabetic patients are high (6.3–7.4% of total National Health System expenditure). Their average annual cost is €1,290–1,476. For individuals without diabetes, the average annual cost is €865.
Comparision of two‐flow cytometry methods for basophil degranulation in patients sensitized to grass pollen
Authors: A. Michova, M. Abugalia, Ts. Ivanova, G. Nikolov, H. Taskov, B. Petrunov
Journal: Allergy (2006)

Background: Two‐flow cytometry methods for quantification of degranulated basophil after allergen‐specific activation were discussed. The methods are discerned by used membrane receptors – Fc ɛ RI or IL‐3R α Our goal was to evaluate the diagnostic potential of the methods and to correlate them to allergen‐specific IgE detection and skin prick test (SPT). Methods: Patient's and control's groups were studied with Bulgarian grass pollen allergen B1 simultaneously by flow cytometry kits: Basotest and BD FastImmune test. Allergy diagnosis was based on clinical history and SPT. The determination of specific IgE was performed by ELISA ‐ RIDASCREEN R . Results: There were no significant differences between the patient's results from Basotest and FastImmune ( P &gt; 0.05). A significant correlation between values, analyzed by Basotest and by FastImmune was found ( r = 0.88). The sensitivity and specificity of the Basotest, FastImmune, specific IgE and SPT were 85%, 72%, 92% and 92% sensitivity and 100%, 92%, 100% and 85% specificity respectively. The efficiency was between 82% and 97%. There were a significant correlation between the specific IgE and flow cytometry tests: tau = 0.92 (Basotest) and tau = 0.71 (FastImmune) and a moderate significant correlation between the SPT and the in vitro tests: tau = 0.26 (Basotest) and tau = 0.31 (FastImmune). Conclusion: The successful use of the Bulgarian grass pollen allergen B1 and both flow cytometry tests was presented. These methods could be as specific tools for IgE‐mediated diagnosis especially FastImmune in the case of low IgE receptor expression.
EXTIRPATION OF THE PINEAL BODY
Authors: Walter E. Dandy
Journal: The Journal of Experimental Medicine (1915)

1. Following the removal of the pineal I have observed no sexual precocity or indolence, no adiposity or emaciation, no somatic or mental precocity or retardation. 2. Our experiments seem to have yielded nothing to sustain the view that the pineal gland has an active endocrine function of importance either in the very young or adult dogs. 3. The pineal is apparently not essential to life and seems to have no influence upon the animal's well being.
Adenosine deaminase activity in the diagnosis of tuberculous peritonitis.
Authors: J M Martinez-Vazquez, I Ocana, E Ribera, R M Segura, C Pascual
Journal: Gut (1986)

We studied the activity of adenosine deaminase in the peritoneal fluid of 66 patients who were divided into five groups according to causes of ascites as follows: tuberculous peritonitis (group I), septic peritonitis (group II), secondary to malignant tumours (group III), miscellaneous conditions (group IV), and control subjects of transudates (group V). In patients with tuberculous peritonitis the enzyme activity was significantly higher than for the rest of the groups (p less than 0.001), and enzyme concentrations in all patients were well above the upper non-tuberculous value. Adenosine deaminase activity in the peritoneal fluid has proved to be a simple and reliable method for early diagnosis of tuberculous peritonitis.
INTRACRANIAL TUMORS IN MENTAL HOSPITAL PATIENTS
Authors: CHAS. P. LARSON
Journal: American Journal of Psychiatry (1940)

In the course of routine autopsy examinations at the Western Washington State Mental Hospital during a two year period, thirty cases of intracranial tumor were found, giving a percentage incidence of 13.5. This figure is so much higher than that of any previously reported study that it cannot be regarded as the true incidence of intracranial tumor in mental hospital populations. The author has no adequate reason to offer for the occurrence of so many intracranial growths in this series of autopsies. No far-reaching conclusions can be based upon such a small group of autopsies (223). Needless to say each case was most carefully studied but this has also been done by many competent examiners on much larger series of mental hospital autopsies. It is hoped that this report will stimulate more thorough and careful analysis of the types and frequency of intracranial tumors in these patients. The tumors were classified as to type utilizing modern neurohistologic techniques and neuropathologic classification. Meningiomas were the commonest type of neoplasm encountered, a finding which coincides with previous reports upon this subject. Gliomas were much less frequent than in the series of cases compiled in general hospitals.
Role of the pituitary and thyroid glands in the decline of minimal O2 consumption with age.
Authors: W D Denckla
Journal: Journal of Clinical Investigation (1974)

Resting O2 consumption rate (BMR) or minimal O2 consumption rate (MOC) declines with age. Data are presented that suggest that a newly described function of the pituitary may be responsible for a considerable part of the total 75% decline in the MOC with age. The new function appears to decrease the responsiveness of peripheral tissues to thyroid hormones. Response curves to injected thyroxine indicated that immature rats were three times more responsive to thyroxine than adult rats. All the major endocrine ablations were performed in this and earlier work, and only pituitary ablation (a) restored in adults part of the responsiveness to thyroxine found in immature rats and (b) arrested the normal age-associated decrease in responsiveness to thyroxine in immature rats. Bovine pituitary extracts were found that decreased the responsiveness of immature rats to thyroxine. Experiments with the new pituitary function suggested a possible endocrine mechanism to explain why partial starvation doubled the lifespan for rats only when started before puberty.
Prevalence of adult atopic dermatitis among nursing staff in a Taiwanese medical center: A pilot study on validation of diagnostic questionnaires
Authors: Cheng-Che E. Lan, Chien-Hung Lee, Yi-Wei Lu, Chi-Ling Lin, Hsiu-Hui Chiu, Tsai-Ching Chou, Stephen Chu-Shung Hu, Ching-Ying Wu, Yi-Ying Kim, Hui-Ju Yang, Yin-Chun Chen, Ching-Shuang Wu, Hui-Yu Hsu, Sheng-Lan Shieh, Hsin-Su Yu, Ying-Chin Ko, Gwo-Shing Chen
Journal: Journal of the American Academy of Dermatology (2009)
Erosive Rheumatoid Arthritis Is Associated with Antibodies That Activate PAD4 by Increasing Calcium Sensitivity
Authors: Erika Darrah, Jon T. Giles, Michelle L. Ols, Herbert G. Bull, Felipe Andrade, Antony Rosen
Journal: Science Translational Medicine (2013)

Autoantibodies from rheumatoid arthritis patients augment the function of PAD4 by decreasing its calcium requirement.
Transgenic Mice: Applications to the Study of the Nervous System
Authors: M G Rosenfeld, E B Crenshaw, S A Lira
Journal: Annual Review of Neuroscience (1988)

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