tbuckley/cabot-search huggingface dataset:
Defective glycine cleavage system in nonketotic hyperglycinemia. Occurrence of a less active glycine decarboxylase and an abnormal aminomethyl carrier protein.
Authors: K Hiraga, H Kochi, K Hayasaka, G Kikuchi, W L Nyhan
Journal: Journal of Clinical Investigation (1981)

The activities of then glycine cleavage system in the liver and brain of patient with nonketotic hyperglycinemia was extremely low as compared with those of control human liver and brain. The activities of glycine decarboxylase (P-protein) and the aminomethyl carrier protein (H-protein), two of the four protein components of the glycine cleavage system, were considerably reduced in both the liver and brain; the extent of reduction was greater in the H-protein. The activity of the T-protein was normal. Purified H-protein from the patient did not react with lipoamide dehydrogenase, and titration of thiol groups with [2,3-14C]N-ethylmaleimide suggested that this H-protein is devoid of lipoic acid. This structural abnormality in the H-protein is considered to constitute the primary molecular lesion in this patient with non-ketotic hyperglycinemia. Immunochemical studies using an antibody specific for P-protein showed that the patient was due to reduction of the catalytic activity of the protein rather than a decrease in the actual amount of the P-protein. Partial inactivation of P-protein could result secondarily from impaired metabolism of glycine resulting from deficiency in the activity of H-protein. However, the H-protein from the patient could stimulate the P-protein catalyzed exchange of the carboxyl carbon of glycine with 14CO2, although the specific activity of the purified H-protein from the patient was only 4% of that of control human H-protein. The content of H-protein in the liver of the patient was approximately 35% of that of control human liver.
Protein Gene Product 9.5 Is Selectively Localized in Parietal Epithelial Cells of Bowman's Capsule in the Rat Kidney
Authors: ISAO SHIRATO, KATSUHIKO ASANUMA, YUKIHIKO TAKEDA, KAYO HAYASHI, YASUHIKO TOMINO
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Parietal epithelial cells (PEC) of Bowman's capsules cover the inner aspect of Bowman's capsules and are believed to contribute to extracapillary lesions of glomerulonephritis such as crescent formation. In glomerular research including cell culture experiments and pathology, differentiation between PEC and podocytes has frequently been a major problem. Immunohistochemistry of the adult rat kidney for protein gene product 9.5 (PGP 9.5), a neuron-specific ubiquitin C-terminal hydrolase, demonstrated selective localization of the immunoreactivity in PEC. At the urinary pole of the glomerulus, immunoreactive PEC were clearly differentiated from proximal tubular cells that were negative for PGP 9.5. In the subcapsular nephrogenic zone of newborn rat kidney, immunoreactivity was observed in almost all cells in the commashaped body and early S-shaped body and selectively in PEC in the late S-shaped body and capillary-stage glomerulus. In rat glomerular disease models (Masugi-nephritis and puromycin aminonucleoside nephrosis), cells that consisted of cellular crescents or adhered to glomerular tufts were positive for PGP 9.5. The selective localization of PGP 9.5 in PEC in rat kidney provides a new cytochemical marker for identifying the cells. Development expression of the protein suggests that PGP 9.5 is involved in the processes of nephrogenesis of rat kidney.
A Phase I Dose-Escalation Study of Danusertib (PHA-739358) Administered as a 24-Hour Infusion with and without Granulocyte Colony-Stimulating Factor in a 14-Day Cycle in Patients with Advanced Solid Tumors
Authors: Roger B. Cohen, Suzanne F. Jones, Charu Aggarwal, Margaret von Mehren, Jonathan Cheng, David R. Spigel, F. Anthony Greco, Mariangela Mariani, Maurizio Rocchetti, Roberta Ceruti, Silvia Comis, Bernard Laffranchi, Jurgen Moll, Howard A. Burris
Journal: Clinical Cancer Research (2009)

This study was conducted to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the i.v. pan-aurora kinase inhibitor PHA-739358, danusertib, in patients with advanced solid tumors.In part 1, patients received escalating doses of danusertib (24-hour infusion every 14 days) without filgrastim (granulocyte colony-stimulating factor, G-CSF). Febrile neutropenia was the dose-limiting toxicity without G-CSF. Further dose escalation was done in part 2 with G-CSF. Blood samples were collected for danusertib pharmacokinetics and pharmacodynamics. Skin biopsies were collected to assess histone H3 phosphorylation (pH3).Fifty-six patients were treated, 40 in part 1 and 16 in part 2. Febrile neutropenia was the dose-limiting toxicity in part 1 without G-CSF. Most other adverse events were grade 1 to 2, occurring at doses >or=360 mg/m(2) with similar incidence in parts 1 and 2. The maximum tolerated dose without G-CSF is 500 mg/m(2). The recommended phase 2 dose in part 2 with G-CSF is 750 mg/m(2). Danusertib showed dose-proportional pharmacokinetics in parts 1 and 2 with a median half-life of 18 to 26 hours. pH3 modulation in skin biopsies was observed at >or=500 mg/m(2). One patient with refractory small cell lung cancer (1,000 mg/m(2) with G-CSF) had an objective response lasting 23 weeks. One patient with refractory ovarian cancer had 27% tumor regression and 30% CA125 decline.Danusertib was well tolerated with target inhibition in skin at >or=500 mg/m(2). Preliminary evidence of antitumor activity, including a partial response and several occurrences of prolonged stable disease, was seen across a variety of advanced refractory cancers. Phase II studies are ongoing.
Molecular diagnosis of tuberculosis: current clinical validity and future perspectives
Authors: A Roth, T Schaberg, H Mauch
Journal: European Respiratory Journal (1997)

The rapid development and availability of a variety of new molecular genetic technologies present the clinician with an array of options for the accurate diagnosis of infectious diseases. This is particularly the case for tuberculosis, since molecular methods have been rapidly introduced into all working areas of the mycobacteriology laboratory. Nucleic acid amplification methods to detect Mycobacterium tuberculosis in clinical specimens are increasingly used as a tool to diagnose tuberculosis. The bulk of recently available data from clinical evaluations performed under routine laboratory conditions indicate that these molecular methods are rapid and sensitive, but yet inferior, to culture with regard to sensitivity and specificity. Therefore, until gene amplification tests have proved to be reliable and quality control procedures exist, their clinical validity remains controversial. Consequently, definition of selected clinical applications of gene amplification to routine diagnosis of tuberculosis is important and need to be discussed. This review will focus on the clinical role of molecular methods in the direct detection and diagnosis of M. tuberculosis in clinical samples. In addition, molecular genetic approaches designed to determine drug susceptibility and to discriminate strains below the species level will be outlined and discussed in terms of their current and future clinical applicability.
Human Glioma Growth Is Controlled by MicroRNA-10b
Authors: Galina Gabriely, Ming Yi, Ravi S. Narayan, Johanna M. Niers, Thomas Wurdinger, Jaime Imitola, Keith L. Ligon, Santosh Kesari, Christine Esau, Robert M. Stephens, Bakhos A. Tannous, Anna M. Krichevsky
Journal: Cancer Research (2011)

MicroRNA (miRNA) expression profiling studies revealed a number of miRNAs dysregulated in the malignant brain tumor glioblastoma. Molecular functions of these miRNAs in gliomagenesis are mainly unknown. We show that inhibition of miR-10b, a miRNA not expressed in human brain and strongly upregulated in both low-grade and high-grade gliomas, reduces glioma cell growth by cell-cycle arrest and apoptosis. These cellular responses are mediated by augmented expression of the direct targets of miR-10b, including BCL2L11/Bim, TFAP2C/AP-2γ, CDKN1A/p21, and CDKN2A/p16, which normally protect cells from uncontrolled growth. Analysis of The Cancer Genome Atlas expression data set reveals a strong positive correlation between numerous genes sustaining cellular growth and miR-10b levels in human glioblastomas, while proapoptotic genes anticorrelate with the expression of miR-10b. Furthermore, survival of glioblastoma patients expressing high levels of miR-10 family members is significantly reduced in comparison to patients with low miR-10 levels, indicating that miR-10 may contribute to glioma growth in vivo. Finally, inhibition of miR-10b in a mouse model of human glioma results in significant reduction of tumor growth. Altogether, our experiments validate an important role of miR-10b in gliomagenesis, reveal a novel mechanism of miR-10b-mediated regulation, and suggest the possibility of its future use as a therapeutic target in gliomas.
Vitamin D Deficiency Promotes Human Breast Cancer Growth in a Murine Model of Bone Metastasis
Authors: Li Laine Ooi, Hong Zhou, Robert Kalak, Yu Zheng, Arthur D. Conigrave, Markus J. Seibel, Colin R. Dunstan
Journal: Cancer Research (2010)

Vitamin D exerts antiproliferative, prodifferentiation, and proapoptotic effects on nonclassic target tissues such as breast. Blood levels of 25-hydroxyvitamin D [25(OH)D], the most sensitive indicator of vitamin D status, are inversely correlated with breast cancer risk; however, a causal relationship between vitamin D deficiency and breast cancer growth in bone has not been assessed. We examined the effect of vitamin D deficiency on the intraskeletal growth of the human breast cancer cell line MDA-MB-231-TxSA in a murine model of malignant bone lesions. Subsets of mice were treated concurrently with osteoprotegerin (OPG) to abrogate bone resorption. Outcomes were assessed by repeated radiographic and end-point micro-computed tomography and histologic analyses. Mice weaned onto a vitamin D-free diet developed vitamin D deficiency within 4 weeks [mean +/- SE serum 25(OH)D: 11.5 +/- 0.5 nmol/L], which was sustained throughout the study and was associated with secondary hyperparathyroidism and accelerated bone turnover. Osteolytic lesions appeared earlier and were significantly larger in vitamin D-deficient than in vitamin D-sufficient mice after 2 weeks (radiographic osteolysis: +121.5%; histologic tumor area: +314%; P < 0.05). Although OPG treatment reduced the size of radiographic osteolyses and tumor area in both groups, tumors remained larger in OPG-treated vitamin D-deficient compared with OPG-treated vitamin D-sufficient mice (0.53 +/- 0.05 mm(2) versus 0.19 +/- 0.05 mm2; P < 0.05). We conclude that vitamin D deficiency promotes the growth of human breast cancer cells in the bones of nude mice. These effects are partly mediated through secondary changes in the bone microenvironment, along with direct effects of vitamin D on tumor growth.
Midterm Results from an International Multicentre Randomised Controlled Trial Comparing Bipolar with Monopolar Transurethral Resection of the Prostate
Authors: Charalampos Mamoulakis, Michael Schulze, Andreas Skolarikos, Gerasimos Alivizatos, Roberto M. Scarpa, Jens J. Rassweiler, Jean J.M.C.H. de la Rosette, Cesare M. Scoffone
Journal: European Urology (2012)
Abciximab (ReoPro, Chimeric 7E3 Fab) Demonstrates Equivalent Affinity and Functional Blockade of Glycoprotein IIb/IIIa and α <sub>v</sub> β <sub>3</sub> Integrins
Authors: Susan H. Tam, Patricia M. Sassoli, Robert E. Jordan, Marian T. Nakada
Journal: Circulation (1998)

Background —Large, randomized, and blinded clinical trials (EPIC, EPILOG, and CAPTURE) have demonstrated that abciximab (ReoPro, chimeric 7E3 Fab) markedly reduces thrombotic events associated with percutaneous transluminal coronary interventions. The marked early benefits at 30 days were sustained at 6 months and 3 years. Initially developed because of its efficacy in blocking GP IIb/IIIa (α IIb /β 3 ) receptors on platelets, abciximab also binds with equivalent affinity to α v β 3 . Methods and Results —This study presents a detailed characterization of the α v β 3 interaction, including the ability of abciximab to (1) bind with comparable affinity to α v β 3 and GP IIb/IIIa, (2) inhibit α v β 3 and GP IIb/IIIa–mediated cell adhesion in vitro with IC 50 values approximating binding K D values, and (3) redistribute between GP IIb/IIIa and α v β 3 integrins in vitro. Conclusions —As an antagonist of not only GP IIb/IIIa but also α v β 3 , abciximab may provide additional clinical benefit in preventing α v β 3 -mediated effects such as thrombin generation, clot retraction, or smooth muscle cell migration and proliferation. Abciximab binds with equivalent affinity to both GP IIb/IIIa and α v β 3 and redistributes between the 2 integrin receptors in vitro. Abciximab has been previously shown to circulate on platelets for up to 2 weeks. Taken together, these findings suggest that abciximab may have the ability to inhibit both GP IIb/IIIa and α v β 3 for extended periods.
Psychotherapy with Patients Receiving Kidney Transplant
Authors: JOHN P. KEMPH
Journal: American Journal of Psychiatry (1967)

The development of depression in patients involved in renal transplantation at the University of Michigan Medical Center demonstrated the need for presurgical and postsurgical psychotherapy. It was found that, among recipients, depression precipitated by the fear of impending death usually occurred prior to surgery, and that this was generally alleviated by a realistic appraisal of the ramifications of the transplantation. Among donors, depressive reactions usually occurred following surgery, precipitated by the feeling of having gotten little reward for maximal sacrifice; this was generally alleviated by encouraging the patient to openly express the hostility hitherto suppressed.
Genome of Acanthamoeba castellanii highlights extensive lateral gene transfer and early evolution of tyrosine kinase signaling
Authors: Michael Clarke, Amanda J Lohan, Bernard Liu, Ilias Lagkouvardos, Scott Roy, Nikhat Zafar, Claire Bertelli, Christina Schilde, Arash Kianianmomeni, Thomas R Bürglin, Christian Frech, Bernard Turcotte, Klaus O Kopec, John M Synnott, Caleb Choo, Ivan Paponov, Aliza Finkler, Chris Soon Heng Tan, Andrew P Hutchins, Thomas Weinmeier, Thomas Rattei, Jeffery SC Chu, Gregory Gimenez, Manuel Irimia, Daniel J Rigden, David A Fitzpatrick, Jacob Lorenzo-Morales, Alex Bateman, Cheng-Hsun Chiu, Petrus Tang, Peter Hegemann, Hillel Fromm, Didier Raoult, Gilbert Greub, Diego Miranda-Saavedra, Nansheng Chen, Piers Nash, Michael L Ginger, Matthias Horn, Pauline Schaap, Lis Caler, Brendan J Loftus
Journal: Genome biology (2013)

Abstract Background The Amoebozoa constitute one of the primary divisions of eukaryotes, encompassing taxa of both biomedical and evolutionary importance, yet its genomic diversity remains largely unsampled. Here we present an analysis of a whole genome assembly of Acanthamoeba castellanii ( Ac ) the first representative from a solitary free-living amoebozoan. Results Ac encodes 15,455 compact intron-rich genes, a significant number of which are predicted to have arisen through inter-kingdom lateral gene transfer (LGT). A majority of the LGT candidates have undergone a substantial degree of intronization and Ac appears to have incorporated them into established transcriptional programs. Ac manifests a complex signaling and cell communication repertoire, including a complete tyrosine kinase signaling toolkit and a comparable diversity of predicted extracellular receptors to that found in the facultatively multicellular dictyostelids. An important environmental host of a diverse range of bacteria and viruses, Ac utilizes a diverse repertoire of predicted pattern recognition receptors, many with predicted orthologous functions in the innate immune systems of higher organisms. Conclusions Our analysis highlights the important role of LGT in the biology of Ac and in the diversification of microbial eukaryotes. The early evolution of a key signaling facility implicated in the evolution of metazoan multicellularity strongly argues for its emergence early in the Unikont lineage. Overall, the availability of an Ac genome should aid in deciphering the biology of the Amoebozoa and facilitate functional genomic studies in this important model organism and environmental host.
Electronic nose versus canine nose: clash of the titans
Authors: R. P. Arasaradnam, C. U. Nwokolo, K. D. Bardhan, J. A. Covington
Journal: Gut (2011)

We read with great interest the article by Sonoda et al 1 on canine scent detection in those with colorectal cancer. The concept of using a dog to detect diseases is not new; there are many reported incidents of dogs barking at their owners (or even trying to bite the leg off of an owner with melanoma!) who are later shown to have the disease.

Several studies have shown that dogs are able to detect, among others, breath, lung, bladder, ovary, prostate and skin cancers. In these reports, the dog is trained to recognise the disease state (in fact, the dog is reminded of these different groups …
Anti-Idiotype Monoclonal Antibody Carrying the Internal Image of Ganglioside GM3
Authors: S Yamamoto, T Yamamoto, R E Saxton, D S Hoon, R F Irie
Journal: JNCI Journal of the National Cancer Institute (1990)

Murine anti-idiotype monoclonal antibodies were generated against a human IgM monoclonal antibody (L612) that recognizes ganglioside GM3 on human melanoma. Hybridomas secreting antibodies that bound specifically to L612 were selected by enzyme-linked immu-nosorbent assay using L612 and three negative control human IgMs, including monoclonal anti-GM2 and anti–GD2 antibodies, as well as purifited serum IgM, as antigen sources. GM3–binding inhibition and cell–binding inhibition assays were used to identify seven antiidiotype monoclonal antibodies that recognized determinants located within the antigen-combining sites of L612. To determine whether these anti-idiotype monoclonal antibodies possessed the internal image of the original antigen, we immunized syngeneic BALB/c mice with one of the anti-idiotype monoclonal antibodies, 4C10, coupled with keyhole limpet hemocyanin. Sera from the immunized mice reacted strongly with an antigen-positive M12 melanoma cell line and with purified GM3. Because L612 detects and kills melanoma tumor cells in vitro and in vivo in the presence of complement without affecting normal tissues, anti-idiotype monoclonal antibodies carrying the internal image of GM3 may be an effective tool for active specific immunotherapy in patients with melanoma. [J Natl Cancer Inst 82: 1757–1760,1990]
Role of Nitric Oxide in Vascular Permeability after Combined Burns and Smoke Inhalation Injury
Authors: KAZUTAKA SOEJIMA, LILLIAN D. TRABER, FRANK C. SCHMALSTIEG, HAL HAWKINS, JEFFREY M. JODOIN, CSABA SZABO, EVA SZABO, LASIO VARIG, ANDREW SALZMAN, DANIEL L. TRABER
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Patients with severe burn and/or smoke inhalation injury suffer both systemic and pulmonary vascular hyperpermeability. We hypothesized that nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) plays a role in the changes in microvascular permeability seen with this injury. To test the hypothesis, we administered mercaptoethylguanidine (MEG), a selective iNOS inhibitor, to conscious sheep subjected to a combined smoke inhalation and third-degree burn injury to 40% of total body surface area. The sheep were surgically prepared for chronic study with lung and prefemoral lymph fistulas in order to estimate microvascular permeability. Both the groups and a control group of animals showed an increase in iNOS protein and message in their lungs. The control animals showed significant increases in either plasma or lymph NO2-/NO3- (NOx) concentration at 24 h after injury, with associated cardiac depression and hemoconcentration. The airway epithelium stained for nitrotyrosine. In the treatment group, NOx did not increase significantly in plasma or lymph throughout the experiment, there was no nitrotyrosine staining, hemodynamic depression was not observed, and the fluid requirement was significantly less than in the control group. Changes in pulmonary microvascular permeability were significantly suppressed by inhibition of iNOS. However, there was no significant difference between the two study groups in the microvascular permeability of burned tissue. These data suggest that NO produced by iNOS plays an important role in the changes in systemic and pulmonary microvascular permeability in combined smoke inhalation/third-degree burn injury, but does not affect the vascular permeability of third-degree-burned tissue in this type of injury.
Systematic Evaluation of Genetic Variants in the Inflammation Pathway and Risk of Lung Cancer
Authors: Eric A. Engels, Xifeng Wu, Jian Gu, Qiong Dong, Jun Liu, Margaret R. Spitz
Journal: Cancer Research (2007)

Abstract Inflammatory responses to environmental exposures, such as tobacco smoke, may play a role in lung carcinogenesis. To test this hypothesis, we studied genetic polymorphisms in the inflammation pathway in relation to lung cancer risk. We evaluated a panel of 59 single nucleotide polymorphisms (SNP) in 37 inflammation-related genes among non-Hispanic Caucasian lung cancer cases (N = 1,553) and controls (N = 1,730) from Houston, Texas. Logistic regression was used to assess associations with lung cancer under a dominant genetic model adjusted for sex, age, and smoking. Haplotypes were estimated with the expectation-maximization algorithm. False-positive report probabilities (FPRP) were calculated for significant associations. Interleukin 1β (IL1B) C3954T was associated with lung cancer [odds ratio (OR), 1.27; 95% confidence interval (95% CI), 1.10–1.47; FPRP 0.148]. Two IL1A SNPs (C-889T and Ala114Ser) were also related to lung cancer (OR, 1.18–1.22), although FPRPs were higher. One IL1A-IL1B haplotype, containing only the IL1B 3954T allele, was associated with elevated lung cancer risk (OR, 1.80; 95% CI, 1.24–2.61). These associations were stronger in heavy smokers, particularly for IL1B C3954T (OR, 1.59; 95% CI, 1.28–1.97; FPRP 0.004). Lung cancer risk was unrelated to polymorphisms in IL1 receptor or antagonist genes. Associations with lung cancer were also seen for SNPs in granulocyte macrophage colony stimulating factor and peroxisome proliferator-activated factor-δ, but FPRPs were high. IL1A and IL1B polymorphisms are associated with increased lung cancer risk, especially among heavy smokers. IL1A and IL1B are critical signals in initiating inflammation. Our results suggest that a dysregulated inflammatory response to tobacco-induced lung damage promotes carcinogenesis. [Cancer Res 2007;67(13):6520–7]