tbuckley/cabot-search huggingface dataset:
Abstract 210: Glionitrin A causes apoptosis and DNA damage-induced S phase arrest in human prostate cancer cells
Authors: Young-Joo Kim, Hak Cheol Kwon, Ji-Hye Yoo, Hyun Ok Yang
Journal: Cancer Research (2010)

Abstract In recent study, we have isolated a new diketopiperazine disulfide, Glionitrin A (GN A), from co-culture broth of a Aspergillus fungal strain KMC901 and a Sphingomonas bacterial strain KMK001, and demonstrated anti-microbial and anti-tumor effects; however, its mechanisms of action are not understood yet. Here, we investigated anti-tumor activity of GN A and its underlying molecular mechanism in human prostate cancer DU145 cells in vitro and in vivo. GN A showed significant cytotoxicity (IC50, 1.5 μM) against DU145 cells through a caspase-8-dependent apoptotic pathway. GN A treatment (0.75 ∼ 3 μM) activated caspase-8, 9 and 3, and also increased formation of truncated BID and expression of BAX protein in a dose-dependent manner. Furthermore, GN A elevated phospho-H2A.X (Ser139), which is known to be phosphorylated by ATM/ATR in response to DNA damage, and activated S phase checkpoint associated with ATM-Chk1/2-Cdc25A pathway. In vivo study performed in nude mice bearing xenografts of DU145 (1×107 cells/mouse, s.c.), GN A dramatically reduced the tumor volume by an average of 38.2% (5 mg/kg, p.o.) and 71.3% (10 mg/kg, p.o.) at the 27-day time point, respectively. These observations may provide aid in better understanding of the mechanism underlying the anti-tumor activity of GN A, which has the potential to be developed into an anti-prostate cancer agent. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 210.
Influence of Age and Sex on Plasma Calcitonin in Human Beings
Authors: L. J. Deftos, M. H. Weisman, G. W. Williams, D. B. Karpf, A. M. Frumar, B. J. Davidson, J. G. Parthemore, H. L. Judd
Journal: New England Journal of Medicine (1980)

THE function of many endocrine glands is influenced by age and sex.1 Only recently have these two factors been shown to influence the secretion of the calcemic peptide hormones parathyroid hormone and calcitonin.2 3 4 To evaluate the effects of age and sex on plasma calcitonin in human beings, we expanded our preliminary studies5 and measured plasma levels of the hormone by radioimmunoassay in 137 normal subjects of both sexes. We found that irrespective of age, the increase in calcitonin in response to calcium infusion was greater in men than in women, but that basal levels of calcitonin and the response to . . .
Mapping for prevention: GIS models for directing childhood lead poisoning prevention programs.
Authors: Marie Lynn Miranda, Dana C Dolinoy, M Alicia Overstreet
Journal: Environmental Health Perspectives (2002)

Environmental threats to children's health--especially low-level lead exposure--are complex and multifaceted; consequently, mitigation of these threats has proven costly and insufficient and has produced economic and racial disparities in exposure among populations. Policy makers, public health officials, child advocates, and others currently lack the appropriate infrastructure to evaluate children's risk and exposure potential across a broad range of risks. Unable to identify where the highest risk of exposure occurs, children's environmental health programs remain mitigative instead of preventive. In this article we use geographic information system spatial analysis of data from blood lead screening, county tax assessors, and the U.S. Census to predict statistically based lead exposure risk levels mapped at the individual tax parcel unit in six counties in North Carolina. The resulting model uses weighted risk factors to spatially locate modeled exposure zones, thus highlighting critical areas for targeted intervention. The methods presented here hold promise for application and extension to the other 94 North Carolina counties and nationally, as well as to other environmental health risks.
The left hemisphere as the redundant hemisphere
Authors: Iris E. C. Sommer, René S. Kahn
Journal: Behavioral and Brain Sciences (2003)

In this commentary we argue that evolution of the human brain to host the language system was accomplished by the selective development of frontal and temporal areas in the left hemisphere. The unilateral development of Broca's and Wernicke's areas could have resulted from one or more transcription factors that have an expression pattern restricted to the left hemisphere.
Sudden and unexpected death in a palliative care unit
Authors: A. Wilcock, V. Crosby
Journal: BMJ (2009)

The mode of death in specialist palliative care units or hospices could inform discussions on cardiopulmonary resuscitation (CPR).1 2 We recently analysed 100 consecutive deaths in our 20 bed unit. All patients had cancer, and the deaths represented half of the 197 admissions over 24 weeks. Mode of death was categorised pragmatically at weekly multidisciplinary team meetings as gradual and expected (an expected death …
Pulmonary Changes in Disseminated Lupus Erythematosus
Authors: J. D. Aitchison, A. W. Williams
Journal: Annals of the Rheumatic Diseases (1956)

Pulmonary manifestations in the "diffuse collagen diseases" are said to be commoner than is generally believed and may overshadow the more typical features (Ellman and Cudkowicz, 1954).Over 80 years ago Kaposi (1872) mentioned intercurrent pneumonia in his original account of the visceral lesions of disseminated lupus erythematosus (D.L.E.).Osler (1904) described a case with pro- longed consolidation of the lower lobe of the left lung.Subsequent accounts have affirmed the frequency of pleurisy in D.L.E.and, to a lesser degree, of pneumonia.Until recently, pulmonary changes in D.L.E.have been regarded as the result of secondary bacterial invasion.The possibility of a primary, non- infective involvement of lung was, however, discussed by Klemperer, Pollack, and Baehr (1941), who were impressed by "waxing and waning bronchopneumonia" imperfectly reflected in the post-mortem findings.The number of observations on this aspect of the disease is still relatively meagre.In the three cases of the disease described here, the lungs were examined with special care.Case Reports Case 1, an unmarried domestic servant, aged 43, had been a healthy woman until August, 1952, when she developed pains in the joints of her hands, severe enough to cause her to be off work for 2 months.During the previous year she had noticed that her fingers became very cold and white in cold weather.In August, 1953, her shoulders and wrists became painful and stiff; later, other limb joints were affected, she felt exhausted, and pyrexia was noted.She was treated with penicillin and sodium salicylate, without apparent improvement.She was admitted to the Royal Infirmary, Aberdeen, in October, 1953.Examination.-Shewas an obese, lethargic woman, temperature was 1020 F., head hair scanty, skin notably dry and scaly.Joints.-Movements of the left shoulder, right elbow, knees and ankles were painful and restricted, and the ankles were slightly swollen.Heart.-The cardiac apex beat could not be felt, there was an apical systolic murmur (Grade III), and the blood pressure was 140/90.Lungs.-Rales were heard over both lungs, par-
Ethinylestradiol increases volume and decreases sinusoidal membrane surface in the rat liver: A stereological analysis
Authors: Beat Hornstein, Lukas Stammler, Leonardo Bianchi, Lukas Landmann
Journal: Hepatology (1992)

Structural alterations of liver parenchyma caused by ethinylestradiol, a synthetic estrogen known to induce cholestasis and to act as a tumor promoter factor, were investigated. Male rats treated with 17α-ethinylestradiol (5 mg/kg body weight for 5 days) were compared with controls (n = 5 each). After perfusion fixation and systematic random sampling, paraffin sections, semithin sections and thin sections were examined observing standard stereological techniques. Ethinylestradiol treatment induced an increase in liver volume by 65% (p < 0.001), which was caused more by hypertrophy (volume of singular hepatocyte + 35%, p < 0.001) than by hyperplasia (number of hepatocytes + 23%, p < 0.001). A decrease in sinusoidal membrane surface density (– 43%, p < 0.005) associated with a decrease in sinusoidal microvillar volume density (– 50%, p < 0.005) were both compensated for by the increase in liver volume. No canalicular alterations were observed. Thus changes in hepatocytes detectable with stereological techniques affect the sinusoidal pole where decreased sinusoidal membrane surface is associated with or reflects a substantial loss of membrane phospholipids. The increased liver volume may constitute an adaptive response compensating for the relative decrease in sinusoidal membrane surface and displays characteristics comparable to those of preneoplastic hepatocytes. (HEPATOLOGY 1992;16:217–223.)
General medicine and visual side effects.
Authors: S Davidson
Journal: BMJ (1979)

this is rarely of clinical significance except in malnourished or geriatric patients.Unlike earlier analogues, and owing to a mainly enterohepatic excretion, the plasma clearance of minocycline is largely independent of renal function.Recent papers' 2 indicate that uraemia is not exacerbated if minocycline is used in cases of renal insufficiency.Finally, we are not aware of anything in the published literature to support the theory that this case of interstitial nephritis had anything but a temporal association with minocycline.
Abstract 1041: Alterations of INPP4B, PIK3CA and pAkt of the PI3K pathway are associated with squamous cell carcinoma of the lung
Authors: Annika Magnussen, Christina Karlsson, Peter Söderkvist, Mats G. Karlsson, Lena K. Thunell
Journal: Cancer Research (2011)

Abstract The aim of the study was to investigate how alterations in the PI3K pathway correlate with the non-small cell lung cancer subtypes squamous cell carcinoma (SSC) and adenocarcinoma (ADCA). We analyzed copy number variation (CNV) and protein expression of the newly identified phosphatase INPP4B, protein expression of pAkt, PDPK1 and PTEN as well as mutational status of PIK3CA and PTEN in 180 lung cancer cases. Nineteen % of all cases displayed loss of INPP4B copy whereas 47% lacked expression. Both CNV and expression analyses showed a correlation between loss of INPP4B and the squamous subtype (RR = 1.44, p = 0.06; RR = 1.86, p = 0.00003). Elevated level of pAkt expression was seen in 63% of all cases and also correlated specifically to SCC (RR = 1.71, p = 0.001). PDPK1 was expressed in 70% of all cases, more in male than female patients, but no difference between the tumor subtypes. Regarding PTEN, 50% of all cases displayed loss of expression, of which seven cases were identified with mutations in the phosphatase or C2 domains. We detected nine cases (5%) of PIK3CA mutations, all identified as the E545K hot spot mutation in the helical domain, all except one in SCC (RR = 1.69, p = 0.05). When analyzing all PI3K pathway components together, we show that patients with at least one alteration in the PI3K pathway are twice as likely to have SCC, than ADCA (RR = 2.01, p = 0.02). Interestingly, we also found a strong correlation between high pAkt expression and PTEN expression, which we speculate can be explained by a feedback-loop via EGR1 and ARF recently proposed by Yu et al, 2009. As comparison, we also analyzed MAPK pathway genes, where we identified fifteen KRAS mutations (8%) and one BRAF mutation (1%), significantly associated to ADCA. The intermediate insulin receptor substrate 1 (IRS-1) is involved in activation of both the PI3K and MAPK pathways and we were interested in studying the Gly972Arg polymorphism previously shown to be associated with prostate, colon and breast cancer. However, we could not detect any associations to any subgroup. In conclusion, we show here that several components of the PI3K pathway, alone and in combination, are correlated to development of squamous cell carcinoma of the lung. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1041. doi:10.1158/1538-7445.AM2011-1041
Abstract 5110: The Inhibition of Poly(ADP-ribose) Polymerase-1 (PARP-1) Significantly Accelerates the Vasculogenesis in a Model of Hind Limb Ischemia
Authors: Zakaria Y Abd Elmageed, Ali H Amin, Devika Nair, Partyka Megan, Souad Belmadani, Khalid Matrougui
Journal: Circulation (2009)

Background: Cardiovascular and metabolic diseases are associated with impaired vasculogenesis in response to ischemia. PARP-1, an abundant nuclear enzyme involved in DNA repair and transcriptional regulation and recognized as a key regulator of cell survival and cell death in response to noxious stimuli in various forms of cardiovascular and metabolic disease. Our hypothesis is to determine whether PARP-1 has a key role in vasculogensis in response to ischemia. Methods and Results: Hind limb ischemia was performed in C57/Bl6 mice for 15 days with and without PARP-1 inhibition using TIQ (PARP-1 inhibitor) or local injection of lentivirus-PARP-1-siRNA. We also used microvascular cultured endothelial cells stimulated with hypoxia with and without PARP-1 inhibition (TIQ and lentivirus-PARP-1-siRNA) and determined the expression of VEGF. Mice treated with TIQ significantly accelerated the recovery of blood flow, as determined with MoorLDI-Laser and X-ray, by 50 – 60% the first week and complete recovery at the second week compared to control. Interestingly, mice locally injected with lentivirus-PARP-1-siRNA significantly accelerated blood flow recovery compared to control. Western blot analysis revealed an increase in VEGF level in muscle from mice treated with TIQ or injected with lentivirus-PARP-1-siRNA compared to control. VEGF release in the conditioned media was increased when cultured endothelial cells were stimulated with hypoxia. In addition, endothelial cells pre-treated with TIQ or transfected with lentivirus-PARP-1-siRNA and then stimulated with hypoxia significantly increased VEGF release in the conditioned media compared control and to cells stimulated with hypoxia. Conclusion: Our novel data provide evidence that PARP-1 plays a key role in the regulation of vasculogenesis in response to ischemia. We demonstrated that the inhibition of PARP-1 enhances earlier the formation of new vessels in response to ischemia through the increase of VEGF release. The inhibition of PARP-1 would be interesting in model of altered vasculogenesis such cardiovascular and metabolic diseases.
Relation of epidermal growth factor receptor expression to goblet cell hyperplasia in nasal polyps
Authors: Pierre-Regis Burgel, Estelle Escudier, Andre Coste, Trang Dao-Pick, Iris F. Ueki, Kiyoshi Takeyama, Jae Jeong Shim, Andrew H. Murr, Jay A. Nadel
Journal: Journal of Allergy and Clinical Immunology (2000)
Angioma Venosum Racemosum with Angiomatous Lesions of Skin and Omentum
Authors: I. Gilbert
Journal: BMJ (1952)

Case 8.-Girl aged 3. Pain, synovial swelling, and effusion in left knee in July, 1949.Warm, tender, moderate swelling and effusion, and almost full movement, at start of treat- ment.X-rays showed no osseous focus and normal joint space.Biopsy showed inguinal glands, superficial and deep, to be positive for tuberculosis on
Interleukin-11 Is the Dominant IL-6 Family Cytokine during Gastrointestinal Tumorigenesis and Can Be Targeted Therapeutically
Authors: Tracy L. Putoczki, Stefan Thiem, Andrea Loving, Rita A. Busuttil, Nicholas J. Wilson, Paul K. Ziegler, Paul M. Nguyen, Adele Preaudet, Ryan Farid, Kirsten M. Edwards, Yeliz Boglev, Rodney B. Luwor, Andrew Jarnicki, David Horst, Alex Boussioutas, Joan K. Heath, Oliver M. Sieber, Irina Pleines, Benjamin T. Kile, Andrew Nash, Florian R. Greten, Brent S. McKenzie, Matthias Ernst
Journal: Cancer Cell (2013)
Imaging and Oncologic Drug Development
Authors: Wafik S. El-Deiry, Caroline C. Sigman, Gary J. Kelloff
Journal: Journal of Clinical Oncology (2006)

For decades anatomic imaging with computed tomography or magnetic resonance imaging has facilitated drug development in medical oncology by providing quantifiable and objective evidence of response to cancer therapy. In recent years metabolic imaging with [18F]fluorodeoxyglucose-positron emission tomography has added an important component to the oncologist's armamentarium for earlier detection of response that is now widely used and appreciated. These modalities along with ultrasound and optical imaging (bioluminescence, fluorescence, near-infrared imaging, multispectral imaging) have become used increasingly in preclinical studies in animal models to document the effects of genetic alterations on cancer progression or metastases, the detection of minimal residual disease, and response to various therapeutics including radiation, chemotherapy, or biologic agents. The field of molecular imaging offers potential to deliver a variety of probes that can image noninvasively drug targets, drug distribution, cancer gene expression, cell surface receptor or oncoprotein levels, and biomarker predictors of prognosis, therapeutic response, or failure. Some applications are best suited to accelerate preclinical anticancer drug development, whereas other technologies may be directly transferable to the clinic. Efforts are underway to apply noninvasive in vivo imaging to specific preclinical or clinical problems to accelerate progress in the field. Because resources are limited, and patient suffering from failed or ineffective therapy continues, a concerted effort is being made to address these issues. Many simultaneous activities involving academia; the pharmaceutical, device, and biotechnology industries; US Food and Drug Administration; National Cancer Institute; Centers for Medicare and Medicaid Services; and specialized networks sponsored by the National Institutes of Health are beginning to address these issues to develop consensus recommendations and progress in this important area.
Gain-of-Function Pyrin Mutations Induce NLRP3 Protein-Independent Interleukin-1β Activation and Severe Autoinflammation in Mice
Authors: Jae Jin Chae, Young-Hun Cho, Geun-Shik Lee, Jun Cheng, P. Paul Liu, Lionel Feigenbaum, Stephen I. Katz, Daniel L. Kastner
Journal: Immunity (2011)
Using patients for teaching can enhance their lives
Authors: M. Rhodes
Journal: BMJ (2003)

The students were in the last firm of their first clinical year, so I asked them if there was something they wanted to do that they hadn't covered. The answer was kidney disease. Now the trouble with kidney disease is that there often isn't much of a history, and, until it gets to end stage failure, there aren't many signs. We base our teaching around patients, and the only patient we had in the practice with anything worthwhile to show the students was a rather depressed 80 year old woman who was struggling with home peritoneal dialysis. I didn't …
Muscle wasting in hTNFtg mice, an animal model for rheumatoid arthritis, due to increased cathepsin L expression
Authors: Silvia Hayer, Martin Willburger, Birgit Niederreiter, Aurica Jelinek, Tetyana Shvets, Josef Smolen, Kurt Redlich
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To investigate skeletal myopathy in a chronic inflammatory, erosive animal model for rheumatoid arthritis, the human tumour necrosis factor transgenic (hTNFtg) mice. <h3>Methods</h3> To evaluate whether hTNFtg mice are suffering from skeletal muscle atrophy, the authors isolated Triceps surae muscles from hTNFtg animals from various time-points of age starting 4 weeks until 16 weeks after birth. Muscle weight and body weight were assessed from these animals. Muscle tissue, muscle weight and bodyweight from age and sex-matched wildtype animals served as controls. To investigate whether tumour necrosis factor (TNF) blockade protects hTNFtg animals from muscle atrophy, 5 female hTNFtg animals were treated with anti-TNF ab (Infliximab, 10mg/kg, 3x per week, ip). Untreated hTNFtg animals served as controls. To identify proteolysis pathways and pro-inflammatory cytokine expression involved in muscle atrophy, the authors performed quantitative real-time PCR for Cathepsin L, B, S, H, D, MMP-9 and Interleukin (IL)-1 and IL-6 from mRNA isolated from muscle tissues of hTNFtg and wildtype animals. To further investigate infiltration of inflammatory cells, muscle tissue sections are stained for macrophages, neutrophils, T cells and B cells and convential hematoxylin/eosin. <h3>Results</h3> The authors demonstrate that hTNFtg mice show significantly less triceps surae muscle weight compared to sex- and age matched wildtype animals. Reductions in muscle weight became already manifest at the early age of 4 weeks and were continuously reduced until week 16. Due to decreased muscle weight, bodyweight was also significantly decreased in hTNFtg animals compared to their wildtype littermates. The authors found a significantly increased mRNA expression levels of Cathepsin L, a lysosomal endopeptidase responsible for muscle protein degradation, in muscles from hTNFtg compared to their wildtype littermates. In contrast, other proteases such as cathepsin B, S, H, D did not reach significantly increased expression levels between these 2 genotypes. Moreover, proinflammatory cytokines such as IL1 and IL6 are also significantly upregulated in muscles from hTNFtg mice. <h3>Conclusion</h3> Despite spontaneous development of chronic inflamed, erosive arthritis, chronic overexpression of TNF leads to skeletal muscle atrophy due to increased tissue-degrading cathepsin L in hTNFtg animals.
A Comparison of Calcium, Vitamin D, or Both for Nutritional Rickets in Nigerian Children
Authors: Tom D. Thacher, Philip R. Fischer, John M. Pettifor, Juliana O. Lawson, Christian O. Isichei, James C. Reading, Gary M. Chan
Journal: New England Journal of Medicine (1999)

Nutritional rickets remains prevalent in many tropical countries despite the fact that such countries have ample sunlight. Some postulate that a deficiency of dietary calcium, rather than vitamin D, is often responsible for rickets after infancy.
Patients' Estimation of Overall Treatment Burden: Why Not Ask the Obvious?
Authors: J. Bernhard
Journal: Journal of Clinical Oncology (2002)

PURPOSE: We investigated the clinical validity of patients’ estimation of overall treatment burden. This measure was expected to be responsive to the wide spectrum of reactions on treatment and thus less precise for specific effects. PATIENTS AND METHODS: After the first chemotherapy within a randomized, double-blind trial of the prophylaxis for delayed emesis (SAKK 90/95), 249 patients documented nausea and vomiting daily for 6 days. Over the whole period, they estimated nausea/vomiting (N/V) burden and overall treatment burden by linear analog-self assessment (LASA) indicators and documented other side effects. RESULTS: At day 6, the two burden indicators were moderately correlated (r = 0.58) in accordance with their different concepts. No, partial, or total control of delayed emesis (days 2 to 6) was reflected in a consistent pattern by both indicators, with a stronger and more significant effect (P < .001) on changes in N/V burden than overall treatment burden. In contrast, toxicity other than N/V, as...