tbuckley/cabot-search huggingface dataset:
THE ANTIGENIC RELATIONSHIP BETWEEN BACILLUS PROTEUS X-19 AND RICKETTSIAE
Authors: M. Ruiz Castaneda
Journal: The Journal of Experimental Medicine (1935)

Two substances differing in immunological behavior as well as in certain chemical properties have been isolated from soluble extracts of B. proteus X-19. Both substances appear to be polysaccharides. The first substance is precipitated from X-19 crude extracts by a relatively low percentage of alcohol and electrolytes (from one to two and a half volumes of alcohol). When purified as far as possible, it gives a negative biuret reaction, a positive Molish and has a nitrogen content of 4 per cent. This material, which we call X factor, has the immunological properties of the common antigenic factor in Proteus X-19 and typhus Rickettsiae, described elsewhere. It has the property of precipitating with typhus serum as well as anti-Proteus serum, even after treatment with hot alkali. The second substance we call P factor, suggesting a material which is proper to Proteus X-19 and has nothing to do with the Weil-Felix reaction. It is obtained from the crude extracts of B. proteus X-19 by treating the fluids from which the X factor has been removed with an excess of alcohol (seven to ten volumes, according to electrolytes in solution). The purified material shows a nitrogen content of a little less than 1 per cent, gives a negative biuret and a positive Molish reaction. The P factor produces precipitates with anti-Proteus serum in considerable dilution, but has no effect on typhus serum. It is quickly destroyed on treating with alkali, a fact in accordance with the results already cited, which were obtained by White with whole extracts of B. proteus X-19. The duality of the X-19 extracts seems to be explained by the isolation of two immunologically different factors; one which is alkali-labile and which is proper to B. proteus X-19; and the other which is alkali-stable and is the common antigenic factor in Proteus X-19 and typhus Rickettsiae.
Deletion of progranulin exacerbates atherosclerosis in ApoE knockout mice
Authors: Ryota Kawase, Tohru Ohama, Akifumi Matsuyama, Takashi Matsuwaki, Takeshi Okada, Taiji Yamashita, Miyako Yuasa-Kawase, Hajime Nakaoka, Kazuhiro Nakatani, Miwako Inagaki, Kazumi Tsubakio-Yamamoto, Daisaku Masuda, Yumiko Nakagawa-Toyama, Makoto Nishida, Yasukazu Ohmoto, Masugi Nishihara, Issei Komuro, Shizuya Yamashita
Journal: Cardiovascular Research (2013)

Progranulin (PGRN) is a multifunctional protein known to be involved in inflammation. However, the relation between PGRN and atherosclerosis remains elusive. The aim of this study was to define the role of PGRN in the development of atherosclerosis.First, we checked the expression levels of PGRN in human atherosclerotic plaques. Immunohistochemical analysis showed that PGRN is strongly expressed in foam cells of atherosclerotic plaques. We also found that PGRN is expressed more abundantly in macrophages than in the smooth muscle cells of atherosclerotic lesions in ApoE(-/-) mice fed a high-fat diet for 12 weeks. Next, PGRN(-/-)ApoE(-/-) mice were generated to investigate the effect of PGRN on the development of atherosclerosis. PGRN(-/-)ApoE(-/-) mice exhibited severe atherosclerotic lesions compared with PGRN(+/+)ApoE(-/-) mice, despite their anti-atherogenic lipid profile. These results are partly due to enhanced expression of inflammatory cytokines, adhesion molecules, and decreased expression of endothelial nitric oxide synthase. In addition, lack of PGRN leads to accumulate excessive cholesterol in the macrophages and alter HDL-associated proteins.PGRN seems to be involved in the pathogenesis of atherosclerosis, possibly by various anti-atherogenic effects, including modulation of local and/or systemic inflammation.
Pediatric Malignant Germ Cell Tumors Show Characteristic Transcriptome Profiles
Authors: Roger D. Palmer, Nuno L. Barbosa-Morais, Emma L. Gooding, Balaji Muralidhar, Claire M. Thornton, Mark R. Pett, Ian Roberts, Dominik T. Schneider, Natalie Thorne, Simon Tavaré, James C. Nicholson, Nicholas Coleman
Journal: Cancer Research (2008)

Abstract Malignant germ cell tumors (GCT) of childhood are rare and heterogeneous neoplasms thought to arise from primordial germ cells. They vary substantially in their natural history and show important clinical differences from their adult counterparts. To address the biological basis for these observations, we have undertaken a comprehensive analysis of global gene expression patterns in pediatric malignant GCTs and compared these findings with published data on adult testicular GCTs (TGCT). Our study included 27 primary tumors and assessed the principal malignant histologic types of pediatric GCT, yolk sac tumor (YST; n = 18), and seminoma (n = 9). Analysis of Affymetrix U133A GeneChip data was performed using the statistical software environment R, including gene set enrichment analysis, with cross-validation at the RNA and protein level. Unsupervised analysis showed complete separation of YSTs and seminomas by global gene expression profiles and identified a robust set of 657 discriminatory transcripts. There was no segregation of tumors of the same histology arising at different sites or at different ages within the pediatric range. In contrast, there was segregation of pediatric malignant GCTs and adult malignant TGCTs, most notably for the YSTs. The pediatric seminomas were significantly enriched for genes associated with the self-renewing pluripotent phenotype, whereas the pediatric YSTs were significantly enriched for genes associated with a differentiation and proliferation phenotype. We conclude that histologic type is the key discriminator in pediatric malignant GCTs and that the observed clinical differences between malignant GCTs of children and adults are mirrored by significant differences in global gene expression. [Cancer Res 2008;68(11):4239–47]
Hepatology: a Textbook of Liver Disease, 4th edition: Edited by Zakim, Boyer. Philadelphia: Saunders, 2003, 230.00, pp 1765. ISBN 0-7216-9051-3
Authors: D H Adams
Journal: Gut (2003)

The fourth edition of Zakim and Boyer’s Hepatology: a Textbook of Liver Disease is published this year and significantly updates the previous edition published in 1996. The work once again comes in two volumes with exactly 100 contributing authors, the majority of whom are from the USA. The book is arranged into four sections. Sections 1–3 are in volume 1 and cover cell biology, biochemistry, and physiology (section 1); the systemic effects of liver disease (section 2); and laboratory methods for evaluating liver disease (section 3). The whole of volume 2 is taken up by section IV covering aetiology, clinical features, diagnosis, and treatment of specific liver diseases subdivided into toxic injury, infection, chronic liver disease, …
A "Neural" Enzyme in Nonbilaterian Animals and Algae: Preneural Origins for Peptidylglycine -Amidating Monooxygenase
Authors: R. M. F. Attenborough, D. C. Hayward, M. V. Kitahara, D. J. Miller, E. E. Ball
Journal: Molecular Biology and Evolution (2012)

Secreted peptides, produced by enzymatic processing of larger precursor molecules, are found throughout the animal kingdom and play important regulatory roles as neurotransmitters and hormones. Many require a carboxy-terminal modification, involving the conversion of a glycine residue into an α-amide, for their biological activity. Two sequential enzymatic activities catalyze this conversion: a monooxygenase (peptidylglycine α-hydroxylating monooxygenase or PHM) and an amidating lyase (peptidyl-α-hydroxyglycine α-amidating lyase or PAL). In vertebrates, these activities reside in a single polypeptide known as peptidylglycine α-amidating monooxygenase (PAM), which has been extensively studied in the context of neuropeptide modification. Bifunctional PAMs have been reported from some invertebrates, but the phylogenetic distribution of PAMs and their evolutionary relationship to PALs and PHMs is unclear. Here, we report sequence and expression data for two PAMs from the coral Acropora millepora (Anthozoa, Cnidaria), as well as providing a comprehensive survey of the available sequence data from other organisms. These analyses indicate that bifunctional PAMs predate the origins of the nervous and endocrine systems, consistent with the idea that within the Metazoa their ancestral function may have been to amidate epitheliopeptides. More surprisingly, the phylogenomic survey also revealed the presence of PAMs in green algae (but not in higher plants or fungi), implying that the bifunctional enzyme either predates the plant/animal divergence and has subsequently been lost in a number of lineages or perhaps that convergent evolution or lateral gene transfer has occurred. This finding is consistent with recent discoveries that other molecules once thought of as "neural" predate nervous systems.
The Connective Tissue Growth Factor/Cysteine- Rich 61/Nephroblastoma Overexpressed (CCN) Family*
Authors: David R. Brigstock
Journal: Endocrine Reviews (1999)

I. Introduction II. The Modular Structure of the Connective Tissue Growth Factor/Cysteine-Rich 61/Nephroblastoma Overexpressed (CCN) Family Members III. Connective Tissue Growth Factor (CTGF) A. Discovery B. Structure of the CTGF gene and protein C. CTGF mRNA production D. CTGF production, secretion, and processing E. CTGF-heparin interactions F. Biological properties of CTGF G. Mechanism of action of CTGF IV. Cyr61 A. Discovery of cyr61 B. Structure of the cyr61 gene and protein C. Cyr61 mRNA production D. Cyr61 production and secretion E. Biological properties of cyr61 F. Mechanism of action of cyr61 V. Nov A. Discovery and structure of nov B. Nov mRNA production C. Biological properties of nov VI. Elm1/WISP-1 VII. Heparin-Induced CCN-Like Protein (HICP)/rCop-1/CTGF-3/WISP-2 VIII. WISP-3 IX. Other CCN-Like Molecules X. Regulation of Cellular Functions by the CCN Family A. Cell cycle control B. Cell adhesion and migration C. Extracellular matrix (ECM) production XI. Biological Processes Involving the CCN...
Transporters and Drug-Drug Interactions: Important Determinants of Drug Disposition and Effects
Authors: Jörg König, Fabian Müller, Martin F. Fromm
Journal: Pharmacological Reviews (2013)

Uptake and efflux transporters determine plasma and tissue concentrations of a broad variety of drugs. They are localized in organs such as small intestine, liver, and kidney, which are critical for drug absorption and elimination. Moreover, they can be found in important blood-tissue barriers such as the blood-brain barrier. Inhibition or induction of drug transporters by coadministered drugs can alter pharmacokinetics and pharmacodynamics of the victim drugs. This review will summarize in particular clinically observed drug-drug interactions attributable to inhibition or induction of intestinal export transporters [P-glycoprotein (P-gp), breast cancer resistance protein (BCRP)], to inhibition of hepatic uptake transporters [organic anion transporting polypeptides (OATPs)], or to inhibition of transporter-mediated [organic anion transporters (OATs), organic cation transporter 2 (OCT2), multidrug and toxin extrusion proteins (MATEs), P-gp] renal secretion of xenobiotics. Available data on the impact of nutrition on transport processes as well as genotype-dependent, transporter-mediated drug-drug interactions will be discussed. We will also present and discuss data on the variable extent to which information on the impact of transporters on drug disposition is included in summaries of product characteristics of selected countries (SPCs). Further work is required regarding a better understanding of the role of the drug metabolism–drug transport interplay for drug-drug interactions and on the extrapolation of in vitro findings to the in vivo (human) situation.
Anterior clinoidal meningiomas: Report of a series of 33 patients operated on through the pterional approach
Authors: Fabrizio Puzzilli, Andrea Ruggeri, Luciano Mastronardi, Antonino Agrillo, Luigi Ferrante
Journal: Neuro-Oncology (1999)

Between 1985 and 1995, 33 cases of clinoidal meningioma were surgically treated by pterional approach.In 6 cases, according to the grading scale of Al-Mefty, the lesions were group I, having originated from the lower part of the clinoid; in 22 cases, the lesions were group II, having originated from the upper or lateral part of the clinoid process; and in 5 cases, the lesions were group III since they arose from the optic foramen.Postoperatively, 17 patients showed an improvement, 4 were unchanged, and 6 presented further de cits.Five patients died after surgery: two from pulmonary thromboembolism, one from myocardial infarction, one from hematoma of the operative eld, and one from cerebral ischemia after severe vasospasm of the internal carotid artery (unresponsive to treatment).The mean follow-up was 53.7 months (range 12-108 months) and included 19 patients.During this period, there were ve recurrences, and three patients underwent resection again and showed no signs of tumor regrowth 1 year later; one patient who did not undergo resection again due to his age and poor general conditions died 3 years after onset of the recurrence; the last patient has so far refused a second operation.The clinical, diagnostic, and therapeutic aspects of this not infrequent pathology are discussed in the light of our experience and the pertinent literature.
Fees for Temporary Residents
Authors: A. R. Jordan
Journal: BMJ (1971)

Change is not always for the better.Which of us wants a pile of near hospitalsized folders on his desk or in his car?As for the option to use the new size-as soon as patients start to move about the country there will no longer be an option; every doctor will have to use some of the new size.We are being offered a few hours of super-efficient note-finding in the distant future for several chaotic years of mixed sizes and unequal filing systems now.No doubt the planners, after their efforts, wish to achieve something.Let them remember: Printnim non nocere.-Iam, etc.,
The descriptive epidemiology of atypical teratoid/rhabdoid tumors in the United States, 2001-2010
Authors: Q. T. Ostrom, Y. Chen, P. M. de Blank, A. Ondracek, P. Farah, H. Gittleman, Y. Wolinsky, C. Kruchko, M. L. Cohen, D. J. Brat, J. S. Barnholtz-Sloan
Journal: Neuro-Oncology (2014)

Atypical teratoid/rhabdoid tumor is a rare malignant CNS tumor that most often affects children ≤3 years old. The Central Brain Tumor Registry of the United States contains the largest aggregation of population-based incidence data for primary CNS tumors in the US. Its data were used to describe the incidence, associated trends, and relative survival after diagnosis of atypical teratoid/rhabdoid tumor. Using data from 50 cancer registries between 2001 and 2010, age-adjusted incidence rates per 100 000 and 95% CIs were calculated by sex, race, Hispanic ethnicity, age at diagnosis, and location of tumor in the CNS for children aged 0 to 19 years. Relative survival rates and 95% CIs were also calculated. The average annual age-adjusted incidence rate was 0.07 (95% CI: 0.07, 0.08). Incidence rates did not significantly vary by sex, race, or ethnicity. Age had a strong effect on incidence rate, with highest incidence among children <1 year, and decreasing incidence with increasing age. The 6-month, 1-year, and 5-year relative survival rates for all ages were 65.0%, 46.8%, and 28.3%, respectively. Atypical teratoid/rhabdoid tumor can occur anywhere in the CNS, but supratentorial tumors were more common with increasing age. We confirm differences in survival by age at diagnosis, treatment pattern, and location of tumor in the brain. This contributes to our understanding of these tumors and may stimulate research leading to improved treatment of this devastating childhood disease.
Donor CD4 T Cells Are Critical in Allogeneic Stem Cell Transplantation against Murine Solid Tumor
Authors: Yoriyuki Kamiryo, Masatoshi Eto, Hisakata Yamada, Toshiki Yajima, Masahiko Harano, Ario Takeuchi, Katsunori Tatsugami, Masumitsu Hamaguchi, Seiji Naito, Yasunobu Yoshikai
Journal: Cancer Research (2009)

Nonmyeloablative allogeneic stem cell transplantation (SCT) has been used for various malignancies, although detailed mechanisms of antitumor effects remain unclear. We showed that a nonmyeloablative allogeneic SCT regimen, which consists of mixed chimerism induced by an injection of donor spleen and bone marrow cells followed by cyclophosphamide treatment and a donor lymphocyte infusion (DLI), exerted antitumor effects on established murine bladder tumor, MBT-2. An expansion of donor CD4 T cells accompanied by transient but vigorous IFN-gamma production was detected shortly after DLI. In vivo neutralization of IFN-gamma or depletion of CD4 T cells from DLI abolished the antitumor effects, indicating an indispensable role of donor CD4 T cells producing IFN-gamma. Donor as well as host CD8 T cells accumulated in the tumor region with time. Importantly, depletion of CD8 T cells from DLI did not reverse the suppression of tumor growth, indicating that CD4 T cells play a more essential role in mediating early antitumor effects. Furthermore, tumor-specific response of host CD8 T cells was suggested. These results not only provide the first evidence of nonmyeloablative allogeneic SCT for the treatment of bladder tumor but also elucidate detailed mechanisms of antitumor effects provoked by DLI.
Conservative treatment of gastrointestinal haemorrhage.
Authors: S B Rofe, J M Duggan, E R Smith, C J Thursby
Journal: Gut (1985)

The Gastroenterology Unit of the Royal Newcastle Hospital treats all acute bleeders in the hospital and has followed a policy of conservative blood transfusion and early surgery directed to gastric ulcer upon rebleeding. A prospective study of 201 consecutive episodes is presented and compared with recent series treated more conventionally. Our patients were transfused less, and operated upon less often with a lower mortality rate in those with chronic peptic ulcers. The data suggest that a reversion to the less aggressive treatment policies of several decades ago, combined with early limited surgery directed to endoscopically proven gastric ulcer is worthy of trial.
Pre-flight hypoxic challenge in infants and young children with respiratory disease
Authors: R Buchdahl
Journal: Thorax (2004)

Modern aircraft flying at high altitude are cabin pressurised to an atmospheric partial pressure of up to 8000 feet (2348 metres), equivalent to breathing approximately 15% oxygen. This may expose individuals with cardiorespiratory disease to the risk of developing hypoxia. In 2002 the British Thoracic Society (BTS) issued recommendations for passengers with respiratory diseases who are planning to fly.1 These recommendations included the use of a hypoxic challenge test in children with a history of respiratory disease too young to undergo conventional lung function tests. While pre-flight hypoxic challenge tests have been evaluated in older children2 and adults3 with respiratory disease, there are few data on hypoxic responses in infants and young children with respiratory disease although one study has observed profound desaturation in a small number of healthy infants while asleep.4

In the last 6 years we have tested …
Artificial Insemination and Public Policy
Authors: S. J. Behrman
Journal: New England Journal of Medicine (1979)

For the healthy wife and infertile husband the choices are accepting the fact of permanent childlessness, adoption or artificial insemination by donor. From available data,1 2 3 it is safe to say that in the United States between 6000 and 10,000 children have been conceived each year as a result of artificial insemination. By simple arithmetic this means that 12,000 to 15,000 couples have requested this procedure and that at least a quarter of a million such offspring born from such practices over the last 20 years must now be living in these United States. But because of the inhibitory social and . . .
A Peptide-Based Positron Emission Tomography Probe for <i>In Vivo</i> Detection of Caspase Activity in Apoptotic Cells
Authors: Matthew R. Hight, Yiu-Yin Cheung, Michael L. Nickels, Eric S. Dawson, Ping Zhao, Samir Saleh, Jason R. Buck, Dewei Tang, M. Kay Washington, Robert J. Coffey, H. Charles Manning
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Apoptosis, or programmed cell death, can be leveraged as a surrogate measure of response to therapeutic interventions in medicine. Cysteine aspartic acid–specific proteases, or caspases, are essential determinants of apoptosis signaling cascades and represent promising targets for molecular imaging. Here, we report development and in vivo validation of [18F]4-fluorobenzylcarbonyl–Val–Ala–Asp(OMe)–fluoromethylketone ([18F]FB-VAD-FMK), a novel peptide-based molecular probe suitable for quantification of caspase activity in vivo using positron emission tomography (PET). Experimental Design: Supported by molecular modeling studies and subsequent in vitro assays suggesting probe feasibility, the labeled pan-caspase inhibitory peptide, [18F]FB-VAD-FMK, was produced in high radiochemical yield and purity using a simple two-step, radiofluorination. The biodistribution of [18F]FB-VAD-FMK in normal tissue and its efficacy to predict response to molecularly targeted therapy in tumors was evaluated using microPET imaging of mouse models of human colorectal cancer. Results: Accumulation of [18F]FB-VAD-FMK was found to agree with elevated caspase-3 activity in response to Aurora B kinase inhibition as well as a multidrug regimen that combined an inhibitor of mutant BRAF and a dual PI3K/mTOR inhibitor in V600EBRAF colon cancer. In the latter setting, [18F]FB-VAD-FMK PET was also elevated in the tumors of cohorts that exhibited reduction in size. Conclusions: These studies illuminate [18F]FB-VAD-FMK as a promising PET imaging probe to detect apoptosis in tumors and as a novel, potentially translatable biomarker for predicting response to personalized medicine. Clin Cancer Res; 20(8); 2126–35. ©2014 AACR.