tbuckley/cabot-search huggingface dataset:
Identification and Characterization of an Activating F229V Substitution in the V2 Vasopressin Receptor in an Infant with NSIAD
Authors: Eric Carpentier, Larry A. Greenbaum, Driss Rochdi, Ravinder Abrol, William A. Goddard, Daniel G. Bichet, Michel Bouvier
Journal: Journal of the American Society of Nephrology (2012)

Gain-of-function mutations in the gene encoding the V2 vasopressin receptor (V2R) cause nephrogenic syndrome of inappropriate antidiuresis. To date, reported mutations lead to the substitution of arginine 137 by either a cysteine or leucine (R137C/L). Here, we describe a 3-month-old hyponatremic infant found to have a phenylalanine 229 to valine (F229V) substitution in V2R. Characterization of this substitution in vitro revealed that it leads to high constitutive activity of the receptor, compatible with spontaneous antidiuresis. In contrast to R137C/L mutant receptors, F229V receptors do not undergo spontaneous desensitization, which results in sustained, high basal activity. Notably, the V2R-selective inverse agonists tolvaptan and satavaptan completely silenced the constitutive signaling activity of the F229V mutant receptor, indicating that this substitution does not lock the receptor in an irreversible active state. Thus, inverse agonists might prove to be effective therapies for treating patients with this or other spontaneously activating mutations that do not lock the V2R in its active state. These results emphasize the importance of genetic testing and the functional characterization of mutant receptors for patients with nephrogenic syndrome of inappropriate antidiuresis because the results might inform treatment decisions.
Specific immunization strategies against oxidized low-density lipoprotein: A novel way to reduce nonalcoholic steatohepatitis in mice
Authors: Veerle Bieghs, Patrick J. van Gorp, Sofie M.A. Walenbergh, Marion J. Gijbels, Fons Verheyen, Wim A. Buurman, David E. Briles, Marten H. Hofker, Christoph J. Binder, Ronit Shiri-Sverdlov
Journal: Hepatology (2012)

Nonalcoholic steatohepatitis (NASH) is characterized by hepatic lipid accumulation combined with inflammation, which can ultimately progress into cirrhosis. Recently, we demonstrated that deletion of scavenger receptors (SRs) CD36 and SR-A in hematopoietic cells reduced hepatic inflammation. In addition to uptake of modified lipoproteins, CD36 and SR-A are also involved in other functions that can activate the inflammatory response. Therefore, the actual trigger for SR activation during NASH is unclear. Here, we hypothesized that hepatic inflammation is triggered by recognition of oxidized LDL (oxLDL) by Kupffer cells (KCs). To inhibit recognition of oxLDL by KCs, low-density lipoprotein receptor ( Ldlr −/− ) mice were immunized with heat-inactivated pneumococci, which were shown to induce the production of anti-oxLDL immunoglobulin M (IgM) antibodies, due to molecular mimicry with oxLDL. The mice received a high-fat, high-cholesterol diet during the last 3 weeks to induce NASH. Immunization with pneumococci increased anti-oxLDL IgM levels and led to a reduction in hepatic inflammation, as shown by reduced macrophage, neutrophil, and T cell infiltration, and reduced gene expression of tumor necrosis factor ( Tnf ), interleukin-6 ( Il-6 ), interleukin-1β ( Il-1b ), monocyte chemoattractant protein 1 ( Mcp1 ), and fibrosis-related genes. In immunized mice, KCs were smaller and showed fewer cholesterol crystals compared with nonimmunized mice. Conclusion: Antibodies to oxLDL play an important role in the pathogenesis of NASH. Therefore, the potential of phosphorylcholine-based vaccination strategies as a novel tool for the prevention and therapy of NASH should be tested in the future.
SIRT1 is required for oncogenic transformation of neural stem cells and for the survival of “cancer cells with neural stemness” in a p53-dependent manner
Authors: Ji-Seon Lee, Jeong-Rak Park, Ok-Seon Kwon, Tae-Hee Lee, Ichiro Nakano, Hiroyuki Miyoshi, Kwang-Hoon Chun, Myung-Jin Park, Hong Jun Lee, Seung U. Kim, Hyuk-Jin Cha
Journal: Neuro-Oncology (2014)

Cancer stemness, observed in several types of glioma stem cells (GSCs), has been demonstrated to be an important barrier for efficient cancer therapy. We have previously reported that cancerous neural stem cells (F3.Ras.CNSCs), derived from immortalized human neural stem cells by a single oncogenic stimulation, form glial tumors in vivo. We searched for a commonly expressed stress modulator in both F3.Ras.CNSCs and GSCs and identified silent mating type information regulation 2, homolog (SIRT1) as a key factor in maintaining cancer stemness. We demonstrate that the expression of SIRT1, expressed in “cancer cells with neural stemness,” is critical not only for the maintenance of stem cells, but also for oncogenic transformation. Interestingly, SIRT1 is essential for the survival and tumorigenicity of F3.Ras.CNSCs and GSCs but not for the U87 glioma cell line. These results indicate that expression of SIRT1 in cancer cells with neural stemness plays an important role in suppressing p53-dependent tumor surveillance, the abrogation of which may be responsible not only for inducing oncogenic transformation but also for retaining the neural cancer stemness of the cells, suggesting that SIRT1 may be a putative therapeutic target in GSCs.
Association of duration of symptoms at presentation with angiographic and clinical outcomes after fibrinolytic therapy in patients with st-segment elevation myocardial infarction
Authors: C. Michael Gibson, Sabina A. Murphy, Ajay J. Kirtane, Robert P. Giugliano, Christopher P. Cannon, Elliott M. Antman, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2004)
Vitamin E Trafficking in Neurologic Health and Disease
Authors: Lynn Ulatowski, Danny Manor
Journal: Annual Review of Nutrition (2013)

Vitamin E was identified almost a century ago as a botanical compound necessary for rodent reproduction. Decades of research since then established that of all members of the vitamin E family, α-tocopherol is selectively enriched in human tissues, and it is essential for human health. The major function of α-tocopherol is thought to be that of a lipid-soluble antioxidant that prevents oxidative damage to biological components. As such, α-tocopherol is necessary for numerous physiological processes such as permeability of lipid bilayers, cell adhesion, and gene expression. Inadequate levels of α-tocopherol interfere with cellular function and precipitate diseases, notably ones that affect the central nervous system. The extreme hydrophobicity of α-tocopherol poses a serious thermodynamic barrier for proper distribution of the vitamin to target tissues and cells. Although transport of the vitamin shares some steps with that of other lipids, selected tissues evolved dedicated transport mechanisms involving the α-tocopherol transfer protein (αTTP). The critical roles of this protein and its ligand are underscored by the debilitating pathologies that characterize human carriers of mutations in the TTPA gene.
Fibroblast growth factor in gastroprotection and ulcer healing: interaction with sucralfate.
Authors: S J Konturek, T Brzozowski, J Majka, A Szlachcic, W Bielanski, J Stachura, W Otto
Journal: Gut (1993)

The study was designed to determine the gastroprotective and ulcer healing efficacy of basic transforming growth factor (bFGF) and to assess whether this peptide contributes to the action of sucralfate on the rat stomach. Application of human recombinant bFGF (1-100 micrograms/kg/hour subcutaneously) failed to affect the formation of acute gastric lesions induced by 100% ethanol and acidified aspirin but reduced the stress induced by gastric lesions. Sucralfate (100-200 mg/kg given orally) protected gastric mucosa against the ethanol, aspirin, and stress induced acute gastric lesions but the addition of bFGF (100 micrograms/kg subcutaneously or intragastrically) failed to affect sucralfate induced protection against ethanol or aspirin but increased that against stress. Administration of bFGF (3-300 micrograms/kg/day) by an intragastric or an intraperitoneal route or sucralfate (400 mg/kg/day) orally to rats with acetic acid induced gastric ulcers, enhanced the healing rate of these ulcers during seven day treatment in a dose dependent manner. This was accompanied by a pronounced increase in the number of capillaries and myofibroblasts and in DNA synthesis and DNA and RNA concentrations in the granulation tissue in the ulcer area. [125I]bFGF (1 microCi) applied subcutaneously or intragastrically accumulated in two to threefold higher amounts in the ulcer area than in the intact mucosa, particularly in rats treated with sucralfate. Concurrent treatment with indomethacin (2 mg/kg intraperitoneally) delayed ulcer healing and reduced the binding of labelled bFGF to the ulcer area, angiogenesis, and DNA synthesis by sucralfate. Addition of [125I]bFGF to sucralfate at various pHs resulted in the coprecipitation of bFGF by sucralfate in a pH dependent manner from about 10% at pH 7.0 to 90% at pH 1.5. Thus bFGF shows little protective activity and is not essential for gastroprotection afforded by sucralfate but plays an important part in healing of gastric ulcers possibly due to its growth promoting and angiogenic actions.
Anonymous sources: where do adult β cells come from?
Authors: Michael S. German
Journal: Journal of Clinical Investigation (2013)

Evidence that the pool of insulin-producing β cells in the pancreas is reduced in both major forms of diabetes mellitus has led to efforts to understand β cell turnover in the adult pancreas. Unfortunately, previous studies have reached opposing conclusions regarding the source of new β cells during regeneration in the adult pancreas. In this issue of the JCI, Xiao et al. use a novel mouse model for detecting new β cells derived from non-β cells to demonstrate the absence of β cell neogenesis from non-β cells during normal postnatal growth and in models of β cell regeneration. This work adds to mounting evidence that in most physiological and pathological conditions, β cell neogenesis may not make large contributions to the postnatal β cell pool - at least not in rodents.
A Foot Care Program for Diabetic Unilateral Lower-Limb Amputees
Authors: Anne L. Carrington, Caroline A. Abbott, Joan Griffiths, Nicky Jackson, Sylvia R. Johnson, Jai Kulkarni, Ernest R.E. Van Ross, Andrew J.M. Boulton
Journal: Diabetes Care (2001)

OBJECTIVE— To assess the efficacy of a specialist foot care program designed to prevent a second amputation and to assess peripheral vascular disease (PVD) and peripheral neuropathy in diabetic unilateral lower-limb amputees. RESEARCH DESIGN AND METHODS— Investigations were carried out in 143 diabetic lower-limb unilateral amputees referred to a subregional rehabilitation center for prosthetic care from a catchment area of ∼3 million people. Peripheral vascular and nerve assessment, education, and podiatry were provided for each patient. RESULTS— For the patients referred to the foot care program,there were no baseline differences between the patients who proceeded to a bilateral amputation (n = 22) and those who remained as unilateral amputees (n = 121) in their level of foot care knowledge and mean neuropathy scores. Mean ankle-brachial pressure index was significantly lower for the bilateral amputees (0.75 ± 0.04) compared with the unilateral amputees (0.90 ± 0.03, mean ± SEM, P &amp;lt; 0.05), but there was no difference in the level of oxygen in the skin. However, the level of carbon dioxide was significantly lower in patients with bilateral amputation (24.21 ± 2.16 vs. 31.20 ± 0.85 mmHg, P &amp;lt;0.03). Overall, the establishment of a specialist foot care program made no impact on contralateral limb amputation (22 of 143, 15.4%) compared with matched patients without the program (21 of 148, 14%) over a 2-year outcome period for each patient. CONCLUSIONS— PVD is more closely associated with diabetic bilateral amputation than neuropathy or level of foot care knowledge. Preventative foot care programs for diabetic unilateral amputees should therefore place greater emphasis on peripheral vascular assessment to identify patients at risk and on the development of timely intervention strategies.
UNILATERAL LOWER LIMBS STRENGTH TRAINING WITH THERA-BAND<sup>®</sup>ELASTIC RESISTANCE BANDS IMPROVES FUNCTIONAL ABILITY AND BALANCE OF THE UNTRAINED CONTRALATERAL LIMB
Authors: S Kordosi, A Beneka, P Malliou, S Rokka, A Gioftsidou, S Tokmakidis
Journal: British Journal of Sports Medicine (2014)

Background Cross-education (CE) is being studied for several decades and refers to the power transfer and proprioception in untrained limb after training of the homologous contralateral limb. Objective To examine whether unilateral strengthening of lower limbs with Thera-Band ® elastic resistance bands is beneficial also for the untrained contralateral limb in functional ability and balance. Design A double blinding randomized prospective study. Setting The study was conducted in the Department of P.E and Sports, Democritus University of Thrace, Greece. Participants 15 healthy physically active students (at least three training per week) were randomly selected to participate. Interventions The participants performed strength training with progressive overload for lower limbs, for 4 weeks, with frequency 3 times per week (12 sessions), duration of 30 minutes with 10 min warm up, 20 min strengthening exercises with Bands (Thera-Band ® ) of quadriceps, hamstrings and gastrocnemius muscles. The exercises were executed at stations from supine, lateral and sitting position (4 sets of 10 reps with 15 sec break between sets). Main outcome measurements A. Balance performance (total stability index as dependent variable of the Biodex Stability test) and b. functional ability (Single leg triple jump hop for distance with distance as dependent variable) at 3 times, before exercise period (pre), at the end (post) and 2 weeks after (retention). The hypothesis was formulated before data collection. Results One way repeated measures Anova revealed improvement for both limbs: a. Stability index trained pre 5.87±1.15, post 3.44±1.11, retention 3.61±1.12 untrained pre 5.90±1.82, post 3.61±1.61, retention 3.20±1.71 b. Triple jump trained pre 3.70±.89, post 4.06±.91, retention 4.01±.88, untrained pre 3.78±.83, post 4.09±.85, retention 4.12±.71. Conclusions Unilateral strength training with Thera-Band® elastic resistance bands at lower limbs is effective in improving functional ability and balance of untrained limb.
Reversal of chemosensitivity and induction of cell malignancy of a non-malignant prostate cancer cell line upon extracellular vesicle exposure
Authors: Kiriaki Panagopoulos, Sam Cross-Knorr, Christen Dillard, Dionysios Pantazatos, Michael Del Tatto, David Mills, Lisa Goldstein, Joseph Renzulli, Peter Quesenberry, Devasis Chatterjee
Journal: Molecular Cancer (2013)

Abstract Background Extracellular vesicle (EV) trafficking is a fundamental cellular process that occurs in cells and is required for different aspects of pathophysiology. EV trafficking leads to changes in cellular function including apoptosis, angiogenesis and proliferation required for increased tumor formation. Results We report several phenotypic changes mediated by EVs isolated from non-malignant and malignant prostate cells as well as patient biopsied prostate tumor samples. EVs can reverse the resistance of prostate cancer cells to camptothecin EVs isolated from non-malignant PrECs (Prostate Epithelial Cells) can reverse soft agar colony formation of malignant DU145 cells, with the reciprocal effect observed. Isolation of EVs from 2 Gleason grade 8 prostate cancer patients significantly induced soft agar colony formation of non-malignant PrECs. We have identified proteins via antibody and Mass spectrometry analysis that may be responsible for the phenotypic changes. Mass spectrometry analysis of protein lysates using ProteoIQ revealed protein candidates associated with gene ontology annotations that may be responsible for this phenotypic change. Ingenuity Pathway Analysis was used to identify statistically relevant canonical pathways and functions associated the protein IDs and expression values obtained using ProteoIQ. Western blot analysis confirmed the increase of 14-3-3 zeta, pRKIP and prohibitin protein levels in PrEC cells co-cultured with patient EVs. 14-3-3 proteins were also found as common proteins of 3 other Gleason grade 8 patients. Conclusion Our study provides a rational basis to further investigate putative proteins, such as 14-3-3 and prohibitin and genetic factors that may be responsible for phenotypic changes that are associated with prostate cancer progression.
Glutamic acid decarboxylase and ICA512/IA-2 autoantibodies as disease markers and relationship to residual β-cell function and glycemic control in young type 1 diabetic patients
Authors: M.M. Zanone, E. Catalfamo, S.L. Pietropaolo, I. Rabbone, C. Sacchetti, F. Cerutti, M. Trucco, P. Cavallo-Perin
Journal: Metabolism (2003)
Survey of spontaneous pneumothoraces in the Royal Air Force
Authors: I. R. Cran, C. A. Rumball
Journal: Thorax (1967)

Nine hundred and ninety-four cases of spontaneous pneumothorax which occurred in Royal Air Force personnel over a period of 22 years are reviewed. They are analysed in relation to age, side of occurrence, activity at the time of onset, and seasonal occurrence. Some clinical and radiological findings are presented and the incidence of recurrence is described (the possible association with emphysematous bullae is mentioned). Methods of treatment are discussed and those found most suitable for the special requirements of R.A.F. personnel are described. Spontaneous pneumothorax is thought to be more commonly diagnosed now and an increasing incidence in the R.A.F. in recent years is demonstrated.
Copper Deficiency in Humans
Authors: D M Danks
Journal: Annual Review of Nutrition (1988)

DOES COPPER DEACIENCY OCCUR IN HUMANS?   236 IS MILD CHRONIC COPPER DEACIENCY A SIGNIACANT NUTRITIONAL PROBLEM IN HUMANS?  236 BIOLOGICAL ROLES OF COPPER ... ... ... ... . ..   ... ... ,   ,,......... 236 COPPER HOMEOSTASIS AND THE TRANSPORT OF COPPER ,   ,... 238 COPPER DEACIENCY IN ANIMALS  240 COPPER DEACIENCY IN HUMAN GENETIC DISEASES  244 SEVERE NUTRITIONAL COPPER DEACIENCY IN HUMANS  245 Circumstances Leading to Severe Copper Deficiency . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 Diagnosis of Severe Copper Deficiency . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 MILD CHRONIC COPPER DEACIENCY IN HUMANS  247 Possible Features of Mild Chronic Copper Deficiency ...... .. . ,   , ........ , 247 Methods of Detecting Mild Chronic Copper Deficiency . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249 DIETARY REQUIREMENTS AND INTERACTIONS . .. ... . . . . . . . . . ... .. .. . . .. . . . . .. . . . .. .. 252
Some aspects of childhood malnutrition as a public health problem.
Authors: J C Waterflow
Journal: BMJ (1974)

much concern to medical politics. The village worker sug gested above is still unacceptable to many doctors and their professional organizations. In rural Punjab research has shown that three-quarters of the health care is provided through local people who have learnt to give injections and practise traditional medicine in response to the people's need. A proposal by the Indian Government to recognize and pro vide training for these people in such subjects as nutrition was defeated (by the medical ldbby. Other countries have medical professions no more liberal than India. Effective ser vices in rural areas continue to be blocked by city-based doctors and nurses striving after and passing laws to main tain and improve training of personnel and standards of health care for the elite who live in their cities-standards of care and qualifications which are out of the reach of the rural people both now and i the foreseeable future.
Randomized phase II–III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial
Authors: J.-L. Pujol, A. Lavole, E. Quoix, O. Molinier, P.-J. Souquet, F. Barlesi, H. Le Caer, D. Moro-Sibilot, P. Fournel, J.P. Oster, P. Chatellain, P. Barre, G. Jeannin, P. Mourlanette, M. Derollez, D. Herman, A. Renault, C. Dayen, P.J. Lamy, A. Langlais, F. Morin, G. Zalcman, V. Westeel, M. Poudenx, J. Mazieres, Y. Martinet, J-P. Gury, N. Baize, P. Dumont, F. Vaylet, P. Foucher, J. Dauba, J. Tredaniel, H. Laize, L. Petit, D. Coëtmeur, H. Doubre, E. Pichon, S. Schneider, F. Goutorbe, R. Gervais, M. Zaegel, S. Dehette, B. Coudert, J-P. Duhamel, A. Dixmier, L. Thiberville, P. Deguiral, H. Monnot, P. Romand, H. Berard, C. Raspaud
Journal: Annals of Oncology (2015)
The Art of Lecturing
Authors: G. P. Meredith
Journal: BMJ (1950)

I am not a theologian, but I was once privileged to attend, at a week-end conference, a lecture by a professor of theology. It was twenty-five years ago and it is still vivid to me to-day. The subject was Amos, of whom I previously knew precisely nothing. By the end of the lecture I had not only a dynamic impression of the character and mes sage of the prophet but also a clear and colourful picture of the contemporary economic, political, and social struc ture of the people of Israel.The professor used no notes. He padded round the room, with his hands behind his back, and wearing felt slippers. From time to time he raised one foot to scratch the calf of the other leg. Now and then he looked at one or other of us directly in the eyes, with a kind of challenging glare. At other times he gazed through the window into the extreme distance, as if looking at Palestine, and describing what he saw, taking our gaze with him. I recall that he pronounced Jahweh with the sort of sound one makes in clearing one's throat.
Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma.
Authors: B Barlogie, W S Velasquez, R Alexanian, F Cabanillas
Journal: Journal of Clinical Oncology (1989)

Based on remarkable activity in refractory lymphomas, a combination of etoposide, cisplatin (both administered by 4-day continuous infusions), cytarabine (Ara-C), and dexamethasone (EDAP) was evaluated in 20 patients with advanced myeloma refractory to standard melphalan and prednisone (MP) and/or vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dexamethasone (VAD) and even to high doses of melphalan (HDM) (seven patients). Forty percent of patients responded regardless of previously recognized risk factors (eg, duration of drug resistance, tumor mass, and serum lactic dehydrogenase [LDH] level). While the median survival was only 4.5 months, patients with good performance (Zubrod less than 2) and low or intermediate tumor stage survived more than 14 months compared with only 2 months for the remaining group. EDAP could be readily administered in the outpatient clinic, but neutropenic fever prompted hospital admission in 80% of patients, half of whom developed penumonia and sepsis, a fatal outcome in four patients. Severe myelosuppression was of short duration, so that subsequent cycles could be administered every 3 to 4 weeks. No serious extramedullary toxicity, including renal toxicity, was encountered. Marrow toxicity and hence infectious complications may be reduced by elimination of Ara-C without compromising treatment efficacy. We conclude that the lack of cross-resistance with VAD and even HDM makes EDAP or a similar combination an attractive regiment to be formally explored in an alternating sequence with VAD in high-risk myeloma.