tbuckley/cabot-search huggingface dataset:
Glial Glutamate Transporters Mediate a Functional Metabolic Crosstalk between Neurons and Astrocytes in the Mouse Developing Cortex
Authors: Brigitte Voutsinos-Porche, Gilles Bonvento, Kohichi Tanaka, Pascal Steiner, Egbert Welker, Jean-Yves Chatton, Pierre J. Magistretti, Luc Pellerin
Journal: Neuron (2003)
Noninfectious Complications of Peritoneal Dialysis
Authors: Brendan B. McCormick, Joanne M. Bargman
Journal: Journal of the American Society of Nephrology (2007)

Noninfectious complications of peritoneal dialysis (PD) are increasing in relative importance due to success in decreasing the rate of PD peritonitis. Mechanical catheter complications are emerging as an important cause of technique failure at the same time as experience with PD is declining in North America. There is also increasing interest in metabolic complications of PD and in glucose-sparing strategies to reduce the risk for hyperglycemia, hyperinsulinemia, and hyperleptinemia. This clinical commentary focuses on these noninfectious complications of PD.
The Subcellular Localization of TRPP2 Modulates Its Function
Authors: Xiao Fu, Yan Wang, Nelli Schetle, Hongyu Gao, Michael Pütz, Gero von Gersdorff, Gerd Walz, Albrecht G. Kramer-Zucker
Journal: Journal of the American Society of Nephrology (2008)

TRPP2, also known as polycystin-2, is a calcium permeable nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease but has also been implicated in the regulation of cardiac development, renal tubular differentiation, and left-to-right (L-R) axis determination. For obtaining further insight into how TRPP2 exerts tissue-specific functions, this study took advantage of PACS-dependent trafficking of TRPP2 in zebrafish larvae. PACS proteins recognize an acidic cluster within the carboxy-terminal domain of TRPP2 that undergoes phosphorylation and mediate retrieval of TRPP2 to the Golgi and endoplasmic reticulum (ER). The interaction of human TRPP2 with PACS proteins can be inhibited by a Ser812Ala mutation (TRPP2(S812A)), thereby allowing TRPP2 to reach other subcellular compartments, and enhanced by a Ser812Asp mutation (TRPP2(S812D)), thereby trapping TRPP2 in the ER. It was found that the TRPP2(S812A) mutant rescued cyst formation of TRPP2-deficient zebrafish larvae to the same degree as wild-type TRPP2, whereas the TRPP2(S812D) mutant was significantly more effective in normalizing the distorted body axis of TRPP2-deficient fish. Surprisingly, the TRPP2(S812D) mutant rescued the abnormalities of L-R asymmetry more effectively than either wild-type or TRPP2(S812A), suggesting that the ER localization of TRPP2 plays an important role in the development of normal L-R asymmetry. Taken together, these findings support the hypothesis that TRPP2 assumes distinct subcellular localizations to exert tissue-specific functions.
Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium.
Authors: W V Williams, Q Fang, D Demarco, J VonFeldt, R B Zurier, D B Weiner
Journal: Journal of Clinical Investigation (1992)

RA is characterized by massive proliferation of synovial tissue, accompanying infiltration of the tissue with CD4+ T lymphocytes, and a genetic linkage to the MHC antigen HLA-DR4. Since T cells are restricted by class II MHC molecules such as DR4, this suggests a direct role for these CD4+ cells in pathogenesis. To investigate T cell receptor (TCR) usage in RA, we used oligonucleotide primers specific for each of the major alpha and beta TCR subfamilies to amplify cDNA derived from whole synovium or synovial tissue T cell lines in a family-specific manner. Detection of amplified DNA was facilitated by utilizing oligonucleotide probes derived from the constant regions of the TCRs. The TCR repertoire present in the synovial T cell lines was quite heterogeneous, with an average of 15 alpha chains and 15.8 beta chains detected. When synovial tissue was analyzed, the predominant TCR subfamilies detected tended to be more restricted, with an average of 4.6 alpha chains and 8.6 beta chains detected. This compared with an average of six alpha chains and 12 beta chains in nonrheumatoid synovial samples. The average percentage of synovia positive per TCR beta family was significantly lower for RA versus non-RA specimens (46.1 vs 65.6%, P = 0.034). These findings indicate that while a polyclonal population of T cells is present in RA synovium, the predominant patterns of TCR transcript expression may be somewhat more restricted, suggesting that TCR-based therapy of RA is possible.
Functional and Evolutionary Insights into Human Brain Development through Global Transcriptome Analysis
Authors: Matthew B. Johnson, Yuka Imamura Kawasawa, Christopher E. Mason, Željka Krsnik, Giovanni Coppola, Darko Bogdanović, Daniel H. Geschwind, Shrikant M. Mane, Matthew W. State, Nenad Šestan
Journal: Neuron (2009)
MPs call for better treatment of court witnesses with mental health problems
Authors: A. O'Dowd
Journal: BMJ (2009)

Witnesses who have mental health problems in court cases are badly treated by the criminal justice system, MPs in the United Kingdom have said.

A report by MPs on the Justice Committee voices deep concerns about victims and witnesses with mental health problems, who are often not recognised by prosecutors as credible witnesses or helped to be a witness.

The report found that the service was failing victims and witnesses with any history of mental distress by dropping cases before they get to court and, where their mental health was in question, failing to support them to give good …
Flow system for automated analysis of maize pollen.
Authors: E Amano
Journal: Environmental Health Perspectives (1981)

Pollen grains are haploid gametes of uniform shape and size, and can be obtained in large quantity. If appropriate traits are used, they can be an excellent material for investigation of rare but important biological events like intracistronic recombinations or mutations induced by very low level of mutagens. This advantage will be further improved, if the laborious counting and examination can be made automatically. For automation of pollen analysis, techniques of flow analysis and image analysis would be applicable. Flow analysis with a optical detector was tested using maize pollen. Pollen grains were transported by gentle suction through a glass capillary which was placed under a microscope. Interruptions of the light path by pollen grains were detected by a silicon photocell after optical magnification and converted into electric pulses. The frequency distribution of pulse height was examined by a multichannel pulse height analyzer. 10(6) pollen grains would be counted and classified within about 30 min for a pollen suspension dilute enough for separation of each pulse. The flow system tested seems promising for detection of Wx mutant pollen in a wx pollen population after iodine staining if illumination of sample particles is improved.
SIR MALCOLM MORRIS, K.C.V.O., F.R.C.S.Ed.
Authors: Ernest Dore.
Journal: British Journal of Dermatology (1924)

Journal Article SIR MALCOLM MORRIS, K.C.V.O., F.R.C.S.Ed. Get access Ernest Dore. Ernest Dore. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 36, Issue 4, 1 April 1924, Pages 139–144, https://doi.org/10.1111/j.1365-2133.1924.tb09173.x Published: 01 April 1924
First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial
Authors: Anton Hagenbeek, Ole Gadeberg, Peter Johnson, Lars Møller Pedersen, Jan Walewski, Andrzej Hellmann, Brian K. Link, Tadeusz Robak, Marek Wojtukiewicz, Michael Pfreundschuh, Michael Kneba, Andreas Engert, Pieter Sonneveld, Mimi Flensburg, Jørgen Petersen, Nedjad Losic, John Radford
Journal: Blood (2008)
COMPARATIVE STUDIES OF THE ISOZYMES OF LACTIC DEHYDROGENASE IN RABBIT AND MAN
Authors: Elliot S. Vesell, John Philip, Alexander G. Bearn
Journal: The Journal of Experimental Medicine (1962)

During development of rabbit tissues, characteristic sequential alterations in the LDH isozyme pattern occur, and consist for liver and muscle in loss of the most rapidly migrating anodal bands, and increased activity in the cathodal bands and slower migrating anodal bands. In heart the reverse changes were observed. Comparison of the isozyme patterns observed in various fetal and adult human tissues suggests that these same sequential alterations probably occur. A species-specific isozyme pattern is obtained in long term culture of rabbit, chick, and human cells. The alterations in tissue culture are characterized by a gradual redistribution of total LDH activity in which there is decreased intensity of rapidly migrating anodal bands. These sequential alterations are independent of the organ of origin. The number of bands observed in the starch gel is partly dependent upon the total activities applied. Isozymes may provide a convenient method for determining the species of origin of cell lines in common use and for investigating the effects of various alterations in the in vitro environment on cells grown in tissue culture.
The type of e-cigarette affects its usefulness in smoking cessation
Authors: Frances Thirlway
Journal: BMJ (2015)

In trying to assess what e-cigarettes mean for public health we are all engaged in futurology, which is why it is so hard to agree.1 However, Gornall’s article and most contributions on this subject (for an exception, see Hitchman and colleagues)2 miss an important factor—the existence of two distinct types. …
The Role of Cellular Accumulation in Determining Sensitivity to Platinum-Based Chemotherapy
Authors: Matthew D. Hall, Mitsunori Okabe, Ding-Wu Shen, Xing-Jie Liang, Michael M. Gottesman
Journal: The Annual Review of Pharmacology and Toxicology (2007)

The platinum (Pt) drugs cisplatin and carboplatin are heavily employed in chemotherapy regimens; however, similar to other classes of drugs, a number of intrinsic and acquired resistance mechanisms hamper their effectiveness. The method by which Pt drugs enter cells has traditionally been attributed to simple passive diffusion. However, recent evidence suggests a number of active uptake and efflux mechanisms are at play, and altered regulation of these transporters is responsible for the reduced accumulation of drug in resistant cells. This review suggests a model that helps reconcile the disparate literature by describing multiple pathways for Pt-containing drugs into and out of the cell.
Autonomic function in hypertension. Are there racial differences?
Authors: R J Parmer, J H Cervenka, R A Stone, D T O'Connor
Journal: Circulation (1990)

Previous biochemical assessment of sympathetic nervous system activity including plasma catecholamines, plasma renin activity, and plasma dopamine-beta-hydroxylase levels has suggested racial differences in the contribution of the sympathetic nervous system to the pathogenesis or maintenance of hypertension. We, therefore, performed physiological and pharmacological studies in white and black subjects with essential hypertension and their age-matched normotensive counterparts to assess autonomic and sympathetic nervous system function. One hundred one male subjects (47 white hypertensive, 17 black hypertensive, 22 white normotensive, and 15 black normotensive subjects) were evaluated for baroreceptor reflex sensitivity to low-pressure (amyl nitrite inhalation) and high-pressure (phenylephrine infusion) stimuli; cold pressor test heart rate and blood pressure responses; and blood pressure response to phentolamine alpha-adrenergic blockade. Hypertensive subjects exhibited an increase in resting heart rate, a decrease in baroreceptor reflex sensitivity, and an exaggerated decline in mean arterial pressure in response to phentolamine. These abnormalities were present to a comparable degree in black and white hypertensive subjects. Cold pressor testing revealed greater increases in heart rate in blacks as compared with whites; however, this racial difference was present regardless of blood pressure status, occurring in black normotensive and black hypertensive subjects to a comparable degree. Cold pressor test blood pressure increments were similar in the four groups. We conclude that both white hypertensive and black hypertensive subjects demonstrate similar abnormalities in autonomic and sympathetic nervous system function including blunting of baroreceptor reflex sensitivity and an increased alpha-adrenergic receptor participation in blood pressure maintenance. The results do not suggest major racial differences in autonomic pathogenetic mechanisms in hypertension.
Molecular Evidence for β-tubulin Neofunctionalization in Retaria (Foraminifera and Radiolarians)
Authors: Yubo Hou, Roberto Sierra, David Bassen, Nilesh K. Banavali, Andrea Habura, Jan Pawlowski, Samuel S. Bowser
Journal: Molecular Biology and Evolution (2013)

Foraminifera and radiolarians are closely related amoeboid protists (i.e., retarians) often characterized by their shells and pseudopodia. Previous studies hypothesized that the unusual "Type 2" β-tubulin (β2) is critically involved in forming helical filaments (HFs), a unique microtubule (MT) assembly/disassembly intermediate found in foraminiferan reticulopodia. Such noncanonical β-tubulin sequences have also been found in two radiolarian species and appear to be closely related to the foraminiferan β2. In this study, we report 119 new β-tubulin transcript sequences from six foraminiferans, four radiolarians, and a related non-retarian species. We found that foraminiferan and radiolarian β2-tubulins share some of the unusual substitutions in the structurally essential and usually conserved domains. In the β-tubulin phylogeny, retarian β2-tubulin forms a monophyletic clade, well separated from the canonical β-tubulin (β1) ubiquitous in eukaryotes. Furthermore, we found that foraminiferan and radiolarian β2-tubulin lineages were under positive selection, and used homology models for foraminiferan α- and β-tubulin hexamers to understand the structural effect of the positively selected substitutions. We suggest that the positively selected substitutions play key roles in the transition of MT to HF by altering the lateral and longitudinal interactions between α- and β-tubulin heterodimers. Our results indicate that the unusual β2-tubulin is a molecular synapomorphy of retarians, and the β-tubulin gene duplication occurred before the divergence of Foraminifera and radiolarians. The duplicates have likely been subjected to neofunctionalization responsible for the unique MT to HF assembly/disassembly dynamics, and/or other unknown physiological processes in retarian protists.
Souvenir Children: Death and Rebirth
Authors: Michal Braun, Lea Baider
Journal: Journal of Clinical Oncology (2007)

Miriam was a 28-year-old woman who came to my office (M.B.) in the psycho-oncology unit, seeking advice and support. Her husband, Jonathan, had died of cancer 2 months earlier in a nearby hospital. I thought that this would be another case of bereavement counseling, with her loss at such a young age. However, I had no idea how this woman was about to challenge my worldview and to raise significant ethical, philosophical, and psychological quandaries. One year and 3 months before their wedding, Jonathan had been diagnosed with angiosarcoma of the heart. The prognosis was clear to both of them. However, Miriam did not think that her husband’s life expectancy would be so short. Jonathan commenced chemotherapy; and, except for the hair loss, he tolerated the treatment well. After hearing the diagnosis, he talked with Miriam about canceling their wedding. She refused, and they were married duringthesameperiodthathewasundergoingchemotherapy. They had been friends for 2 years before deciding to marry, and she described their relationship as “two lonely wolves who had found one another.” They loved each other very much, had created a small, insulated world for themselves, and both had difficulty with external social interactions. Miriam revealed that during her husband’s illness, they had been undergoing invitro fertilization (IVF) to try to have a baby. When Jonathan died, she was in the middle of an IVF cycle and actually had completed it at the time of the Shiva (Jewish ritual of mourning during the first week after the death of an immediate family member). Miriam was the only one who knew about it, besides Jonathan and the medical team. She still had his frozen sperm, and it was clear that she would use it in order to become pregnant with Jonathan’s baby. Miriam and her husband had never talked about this possibility. In retrospect, she felt that Jonathan would have opposed it. While listening to Miriam’s story, I questioned the inequitable paradox of going through fertility treatments while facing death and the offer to bank sperm to newly diagnosed cancer patients with a poor prognosis. THE PARADOX OF FERTILITY AND ADVANCED CANCER
Reply to G. Bogani et al
Authors: Brian M. Slomovitz, Robert L. Coleman
Journal: Journal of Clinical Oncology (2015)

We thank Bogani et al for their review of our article and their interesting comments. As we reported in our study, serous histology was associated with a lower response to therapy. The patients with grade 3 histology, however, were more likely to have a clinical benefit than patients with serous cancers (50% v 11%; P .018). The difference between grade 3 cancers was not statistically different from grade1 and 2 cancers (65%). In addition, we are not aware of existing data showing that patients with pretreated, recurrent endometrial cancer have a worse prognosis on the basis of histology. Our group has previously reported on single-agent activity with everolimus. The clinical benefit rate was 21%, and no patients demonstrated an objective response. Ma et al from the National Cancer Institute of Canada reported the single-agent activity of letrozole in a similar cohort to be 9.4%. Although cross-trial comparisons are not favored, the clinical benefit rate and response rate (40% and 32%, respectively) in this current study is favorable compared with the single-agent activity. In our trial, we also demonstrated a relatively favorable toxicity profile. We agree that there are alternatives for patients with recurrent endometrial cancer, particularly if they do not have systemic disease. Specifically, our exclusion criteria included patients who have isolated recurrences (vaginal, pelvic, or paraaortic) that are amenable to potentially curative treatment with radiation therapy or surgery. Unfortunately, patients with recurrent endometrial cancer often do not have curative disease, and we need to increase the successful treatment options. Our current randomized phase II trial of everolimus and letrozole or hormonal therapy (NCT02228681) will certainly help to determine if mammalian target of rapamycin inhibition should be used as an alternative to hormonal therapy in the management of this disease.
Identification of malignant plasma cell precursors in the bone marrow of multiple myeloma.
Authors: F Caligaris-Cappio, L Bergui, L Tesio, G Pizzolo, F Malavasi, M Chilosi, D Campana, B van Camp, G Janossy
Journal: Journal of Clinical Investigation (1985)

Precursors of plasma cells were studied in the bone marrow of 28 patients with multiple myeloma, plasma cell leukemia, and benign monoclonal gammopathy. Pre-B and B cell populations were analyzed with anti-B monoclonal antibodies corresponding to the clusters standardized at the Leucocyte Typing Workshops in Paris and Boston (CD9, CD10, CD19-22, CD24). In advanced forms of plasma cell malignancies, such as cases of multiple myeloma in stages II and III and of plasma cell leukemia, some cells of lymphoid morphology expressed common acute lymphoblastic leukemia antigen (CALLA, CD10) and HLA-DR, but contained no detectable terminal deoxynucleotidyl transferase enzyme. These CALLA+ cells were absent in benign monoclonal gammopathies. In multiple myeloma, the CALLA+ cells were negative for surface and cytoplasmic immunoglobulins (Ig), and, unlike CALLA+, terminal deoxynucleotidyl transferase (TdT+) pre-B cells in the normal bone marrow also failed to react with antibodies to B cell-associated antigens such as CD9, CD19, CD22, and CD24. The CALLA+, Ig- cells could be regarded as preplasmacytic since, after having been separated and stimulated with the phorbol ester 12-0-tetradecanoyl-phorbol-13 acetate in vitro, they transformed into plasma cells and synthesized the same heavy and light chains as myeloma cells.
Mcl-1 and FBW7 Control a Dominant Survival Pathway Underlying HDAC and Bcl-2 Inhibitor Synergy in Squamous Cell Carcinoma
Authors: Lei He, Kristine Torres-Lockhart, Nicole Forster, Saranya Ramakrishnan, Patricia Greninger, Mathew J. Garnett, Ultan McDermott, Stephen M. Rothenberg, Cyril H. Benes, Leif W. Ellisen
Journal: Cancer Discovery (2012)

Effective targeted therapeutics for squamous cell carcinoma (SCC) are lacking. Here, we uncover Mcl-1 as a dominant and tissue-specific survival factor in SCC, providing a roadmap for a new therapeutic approach. Treatment with the histone deacetylase (HDAC) inhibitor vorinostat regulates Bcl-2 family member expression to disable the Mcl-1 axis and thereby induce apoptosis in SCC cells. Although Mcl-1 dominance renders SCC cells resistant to the BH3-mimetic ABT-737, vorinostat primes them for sensitivity to ABT-737 by shuttling Bim from Mcl-1 to Bcl-2/Bcl-xl, resulting in dramatic synergy for this combination and sustained tumor regression in vivo. Moreover, somatic FBW7 mutation in SCC is associated with stabilized Mcl-1 and high Bim levels, resulting in a poor response to standard chemotherapy but a robust response to HDAC inhibitors and enhanced synergy with the combination vorinostat/ABT-737. Collectively, our findings provide a biochemical rationale and predictive markers for the application of this therapeutic combination in SCC.
Viral-mediated Inhibition of Antioxidant Enzymes Contributes to the Pathogenesis of Severe Respiratory Syncytial Virus Bronchiolitis
Authors: Yashoda M. Hosakote, Paul D. Jantzi, Dana L. Esham, Heidi Spratt, Alexander Kurosky, Antonella Casola, Roberto P. Garofalo
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children, for which no specific treatment or vaccine is currently available. We have previously shown that RSV induces reactive oxygen species in cultured cells and oxidative injury in the lungs of experimentally infected mice. The mechanism(s) of RSV-induced oxidative stress in vivo is not known.To measure changes of lung antioxidant enzymes expression/activity and activation of NF-E2-related factor 2 (Nrf2), a transcription factor that regulates detoxifying and antioxidant enzyme gene expression, in mice and in infants with naturally acquired RSV infection.Superoxide dismutase 1 (SOD 1), SOD 2, SOD 3, catalase, glutathione peroxidase, and glutathione S-transferase, as well as Nrf2 expression, were measured in murine bronchoalveolar lavage, cell extracts of conductive airways, and/or in human nasopharyngeal secretions by Western blot and two-dimensional gel electrophoresis. Antioxidant enzyme activity and markers of oxidative cell injury were measured in either murine bronchoalveolar lavage or nasopharyngeal secretions by colorimetric/immunoassays.RSV infection induced a significant decrease in the expression and/or activity of SOD, catalase, glutathione S-transferase, and glutathione peroxidase in murine lungs and in the airways of children with severe bronchiolitis. Markers of oxidative damage correlated with severity of clinical illness in RSV-infected infants. Nrf2 expression was also significantly reduced in the lungs of viral-infected mice.RSV infection induces significant down-regulation of the airway antioxidant system in vivo, likely resulting in lung oxidative damage. Modulation of oxidative stress may pave the way toward important advances in the therapeutic approach of RSV-induced acute lung disease.