tbuckley/cabot-search huggingface dataset:
334. Treatment of Anemia in Mice with Chronic Renal Failure Utilizing Erythropoietin-Secreting Genetically-Engineered Murine Bone Marrow Stromal Cells
Authors: Nicoletta Eliopoulos, Raymonde F. Gagnon, Moira Francois, Jacques Galipeau
Journal: Molecular Therapy (2005)

Top of pageAbstract
Use of recombinant erythropoietin (Epo) for treatment of anemia arising from chronic renal failure is associated with undesirable aspects which may be overcome by utilizing autologous bone marrow stromal cells (MSCs) genetically-engineered to secrete plasma soluble Epo. The aim of the present study was to determine if the anemia in mice with chronic renal failure can be improved with murine Epo gene-modified syngeneic MSCs delivered as a subcutaneous implant. MSCs from normal C57Bl/6 mice were genetically-engineered with retroviral particles encoding for murine Epo. A monoclonal population of resulting Epo+ MSCs, determined by ELISA to secrete 3.7 Units of Epo per million cells per 24 hours, was embedded in the collagen-based matrix Contigen|[trade]|, at different cell densities. Syngeneic mice rendered anemic by right kidney electrocoagulation and subsequent left nephrectomy were implanted subcutaneously with 0.5ml of Epo+ MSCs in matrix. The hematocrit (Hct) of these mice which had decreased following experimental renal failure increased subsequent to the subcutaneous administration of the Epo+ MSCs, depending on the cell density. Implants of 3 million Epo+ MSCs per mouse had no effect on Hct, whereas 10 million Epo+ MSCs per mouse engendered a strong supraphysiological Hct effect. However, in mice that each received 4.5 million Epo+ MSCs or 7.5 million Epo+ MSCs, the Hct that had dropped from basal 56.5 |[plusmn]| 0.56% or 55.0 |[plusmn]| 0.65% to 39.8 |[plusmn]| 1.06% or 40.2 |[plusmn]| 0.81% post-induction of renal failure, rose to 53.5 |[plusmn]| 3.95% or 62.5 |[plusmn]| 5.52% 3 weeks following Epo+ MSCs implantation, and remained above 47.5 or 53.5%, respectively, for over 19 weeks post-implantation (see figure). In contrast, in mice with experimental renal failure that were each implanted with 7.5 million control vector gene-modified MSCs (Control MSCs), the Hct was persistently low, at values of 39-44% (see figure). Blood urea nitrogen (BUN) concentration was determined over time and revealed similar elevated BUN levels, about 4-fold increased, in all groups of mice following experimental renal failure, thus indicating comparable renal disease. Moreover, mice with renal failure implanted with Epo+ MSCs, as compared to those implanted with Control MSCs, showed greater exercise capacity as assessed by a swimming endurance test. In conclusion, our results demonstrate that the implantation of Epo-secreting genetically-engineered MSCs as a subcutaneous neo-organoid can overcome the decrease in Hct occurring in a murine model of renal failure.
ACUTE PORPHYRIA PROVOKED BY BARBITURATES GIVEN WITH ELECTROSHOCK THERAPY
Authors: JOSEPH MANN
Journal: American Journal of Psychiatry (1961)

Porphyria in a patient can, under certain circumstances, especially when under barbiturates, produce symptoms of an emotional disorder, which do not respond to the psychiatrically oriented therapies, but must be treated medically. There is a possibility that in many cases diagnosed primarily as "mental disorder," "hysteria" or other "emotional disturbance," a hidden factor of prophyria exists, which can be easily determined by laboratory testing. It is needless to state that this evaluation could be beneficial in the successful diagnosis and treatment of some patients now in mental hospitals.
Stability of Reacted Reagent Strips (Chemstrips) for Blood Glucose Determinations
Authors: Paul Kubilis, Arlan L Rosenbloom, Pat Cimino, Eric D Rosenbloom
Journal: Diabetes Care (1981)

Reacted Chemstrips were placed in an unsealed envelope or in desiccator vials which were opened daily after 1, 2, 3, 4, 5, 6, 7, and 14 days. The time of change of the reading for 2 days in a row by all three observers was noted. Readings in the low and normal range were most stable and can be considered reliable for 2–3 days when protected from light. If in a desiccator tube, the strips can be reliably reread when the tube is opened as long as 7 days later. In a separate study, strips were left exposed on the laboratory bench or placed in a vial and read frequently for 6 h and again at 28 h. This exposure, comparable to the CS being taped to a hospital record, results in reading changes as early as 2 h after reaction.
Abstract 2969: A Novel pathway for regulation of ANXA2 expression in lung cancer cell metastasis by SETDB1/SMAD3 repressor complex.
Authors: Tsai-Yu Tzeng, Ming-Ta Hsu
Journal: Cancer Research (2013)

Abstract Aberrant histone methylation contributes to tumor development and progression by histone methyltransferase. SETDB1 is an H3K9 methyltransferase that contributes to the epigenetic silencing of target genes in cancer cells, but the role of SETDB1 in the progression of tumorigenesis remains largely unknown. We show here that H3K9Me2 and SETDB1 are down-regulated in metastatic lung cancer cell lines. Immunohistochemistry examination of the lung carcinoma tissue microarray revealed that expression of SETDB1 is significant decreased in metastasis status. Ectopic expression of SETDB1 in highly invasive lung cancer cells suppressed cancer cell migration, invasion and filopodia formation. In contrast, knockdown of endogenous SETDB1 in non-invasive lung cancer cells by RNA interference increases cell migration and invasion in vitro. Mechanistic investigations suggested that SETDB1 is specifically down-regulated by miR-29b in metastatic lung cancer cells. Ectopic miR-29b expression in non-invasive lung cancer cells increases cell invasion ability. Furthermore, we also establish a causal role for the SETDB1/SMAD3 complex in driving metastasis and identify ANXA2 as a critical target in this process among numerous target genes. These findings suggest a novel pathway regulated by SETDB1/SMAD3 complex in lung cancer metastasis. Citation Format: Tsai-Yu Tzeng, Ming-Ta Hsu. A Novel pathway for regulation of ANXA2 expression in lung cancer cell metastasis by SETDB1/SMAD3 repressor complex. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2969. doi:10.1158/1538-7445.AM2013-2969
Burden of non-communicable diseases in South Asia: Authors' reply
Authors: Abdul Ghaffar, K Srinath Reddy, Monica Singhi
Journal: BMJ (2004)

Future of Kerala depends on its willingness to learn from pastEditor-The Kerala model in health, cited by Bhutta et al in the theme issue on health in South Asia as replicable for South Asian countries, 1 is facing serious threats.The state has a triple burden of communicable, non-communicable, and traumatic diseases.Stupendous growth of the private sector has resulted in skyrocketing healthcare costs.Lured by the hi tech sophistication of the private sector, people are abandoning basic principles of primary health care.Even poor people prefer private hospitals, and a major reason for sustaining poverty is healthcare cost. 2 The government is reducing its investments in health and education due to fiscal crises and pressure from funding and lending agencies.The opening up of the medical education sector to private entrepreneurs, lack of guidelines for the private practice of government doctors, and shortage of doctors for rural areas are all disturbing developments.Transfer of healthcare institutions under local self-governments is yet to show the desired benefits.The state is developing a long term plan, "Health Vision Kerala 2025," and a health policy.To equip the primary healthcare workforce to face the emerging challenges, 3 job responsibilities were redefined recently.Factors that determined the successful Kerala model, among others, include historically prevalent social justice, commitment of governments to health and education, land reforms, an organised public distribution system, streamlined primary health care, and an organised labour sector.Deterioration in these determinants is likely to have strong negative impact.Kerala should learn from its past to avoid the sad plight of some other Indian states.
Effects of a Law against Early Postpartum Discharge on Newborn Follow-up, Adverse Events, and HMO Expenditures
Authors: Jeanne M. Madden, Stephen B. Soumerai, Tracy A. Lieu, Kenneth D. Mandl, Fang Zhang, Dennis Ross-Degnan
Journal: New England Journal of Medicine (2002)

Concern about harm to newborns from early postpartum discharges led to laws establishing minimum hospital stays in the mid-1990s. We evaluated the effects of an early-discharge protocol (a hospital stay of one postpartum night plus a home visit) in a health maintenance organization (HMO) and a subsequent state law guaranteeing a 48-hour hospital stay.Using interrupted-time-series analysis and data on 20,366 mother-infant pairs with normal vaginal deliveries, we measured changes in length of stay, newborn examinations on the third or fourth day of life, and office visits, emergency department visits, and hospital readmissions for newborns. We also examined expenditures for hospitalizations and home-based care.The early-discharge program increased the rate of stays of less than two nights from 29.0 percent to 65.6 percent (P<0.001). The rate declined to 13.7 percent after the state mandate (P<0.001). The rate of newborn examinations on the third or fourth day of life increased from 24.5 percent to 64.4 percent with the program (P<0.001), then dropped to 53.0 percent after the mandate (P<0.001)--changes that primarily reflected changes in the rate of home visits. The rate of nonurgent visits to a health center increased from 33.4 percent to 44.7 percent (P<0.001) after the reduced-stay program was implemented. There were no significant changes in the rate of emergency department visits (quarterly mean, 1.1 percent) or rehospitalizations (quarterly mean, 1.5 percent). Results were similar for a vulnerable subgroup with lower incomes, younger maternal age, a lower level of education, or some combination of these characteristics. Average HMO expenditures on hospital and home-based services decreased by $90 per delivery with the early-discharge program and increased by $100 after the mandate.Neither policy appears to have affected the health outcomes of newborns. After the mandate, newborns were less likely to be examined as recommended on day 3 or 4. Because of changes in hospital prices, the two policies had minimal effects on HMO expenditures for hospital and home-based services.
Abstract LB-385: The role of tumor suppressing microRNA let-7 in undifferentiated nasopharyngeal carcinoma
Authors: TS Wong, W Gao, JZH Li, JYW Chan
Journal: Cancer Research (2012)

Abstract AIMS:This study aimed at evaluating the potential anti-proliferative effects of the microRNA let-7 family in nasopharyngeal carcinoma (NPC) cells. In addition, the association between let-7 suppression and DNA hypermethylation is examined. MATERIALS AND METHODS:Levels of mature let-7 family members (-a, -b, -d, -e, -g, and -i) in normal nasopharyngeal cells (NP69 and NP460) and nasopharyngeal carcinoma cells (HK1 and HONE1) were measured by real-time quantitative PCR. Cell-proliferation assay and c-Myc immunohistochemical staining were performed on NPC cells transfected with let-7 precursor molecules. In addition, expression changes in let-7 family members in response to demethylating agents (5-azacytidine and zebularine) were also examined. RESULTS:In comparison with the normal nasopharyngeal cells, let-7 (-a, -b, -d, -e, -g, and -i) levels were reduced in nasopharyngeal carcinoma cells. Ectopic expression of the let-7 family in nasopharyngeal carcinoma cells resulted in inhibition of cell proliferation through downregulation of c-Myc expression. Demethylation treatment of nasopharyngeal carcinoma cells caused activation of let-7 expression in poorly differentiated nasopharyngeal carcinoma cells only. CONCLUSION:Our results suggested that miRNA let-7 might play a role in the proliferation of NPC. DNA methylation is a potential regulatory pathway, which is affected when let-7 is suppressed in NPC cells. However, the extent of DNA hypermethylation/hypomethylation in regulating let-7 expression requires further elucidation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-385. doi:1538-7445.AM2012-LB-385
What Keeps the Home Fires Burning?
Authors: Susan P. Baker
Journal: New England Journal of Medicine (1992)

The article on residential fires by Runyan and her colleagues1 in this issue of the Journal highlights a continuing plague. Residential fires are the leading cause of death due to injury among children in one fifth of all U.S. states.2 Among children one to four years of age, the number of deaths in home fires surpasses the number due to cancer. Among the elderly, rates of death due to fires are even higher than those among children.3 In the past six decades, the rate of death due to unintentional injuries overall dropped by 65 percent, but for house fires the . . .
Dignity Therapy: Advancing the Science of Spiritual Care in Terminal Illness
Authors: Betty Ferrell
Journal: Journal of Clinical Oncology (2005)

In this issue of theJournalofClinicalOncology, Chochinov et al 1 make a major contribution to advancing care for the terminally ill through their study “Dignity Therapy: A Novel Psychotherapeutic Intervention for Patients Near the End of Life.” This international study, testing a novel intervention to address dignity and meaning in the final days of life, was conducted in Canada and Australia; however, it has significance for other countries attempting to address this highly neglected aspect of health care. The investigators have advanced an area of palliative care that has been cited in recent years by groups such as the WHO, Institute of Medicine, National Cancer Institute, and others as being in serious need of improvement. Many clinicians and institutions have struggled to advance the most basic aspects of care in advanced disease, such as improvements in the treatment of pain and symptoms or treatment of common psychological problems such as anxiety and depression. These investigators, however, have advanced an aspect of terminal care that is perhaps far more challenging than titrating doses of opioids. “Dignity therapy,” which addresses psychosocial and existential distress, is of great importance and shows promise as a novel intervention to diminished suffering and distress in end-of-life care. Several characteristics of this intervention are noteworthy.
Abstract 997: Stability of β-catenin decides the tumor suppressive effect of MRJ
Authors: Mitchell E. Menezes, Aparna Mitra, Lalita A. Shevde, Rajeev S. Samant
Journal: Cancer Research (2011)

Abstract Mammalian relative of DnaJ (MRJ), is a member of the heat shock protein 40 family. We have found that MRJ is lost in advanced grades of breast cancer. Functional studies showed that ectopic expression of the large spliced variant of MRJ, MRJ(L), results in reduced malignant properties as indicated by reduced motility, migration, invasion and soft agar colonization. Furthermore, xenograft studies in athymic mice showed that MRJ(L) expression reduced tumor growth and metastasis. Our investigations also revealed that Wnt/β-catenin signaling is one of the pathways impacted by MRJ(L) expression. Specifically, we found that MRJ(L) expression led to enhanced degradation of β-catenin. Our studies showed that MRJ(L) mediated its tumor suppressive effects by upregulation of DKK1, a negative regulator of Wnt/β-catenin signaling, which promotes proteosome mediated degradation of β-catenin. Hence, we hypothesized that introduction of a degradation-resistant form of β-catenin will lead to restoration of malignant attributes of the MRJ(L) expressing cells. S37A mutation of β-catenin has been known to render it insensitive to ubiquitination-mediated proteosomal degradation. We established stable clones co-expressing S37A β-catenin and MRJ(L). Our analysis of these clones showed that the TCF/LEF activity, as a measure of Wnt/β-catenin signaling, was elevated 10 fold, as measured by the increased activity of the luciferase reporter, TOPFlash. We also found that downstream transcriptional target of Wnt/β-catenin signaling, cyclin D1 showed increased expression in S37A β-catenin clones as compared to the MRJ(L) expressors. Synchronized cell cycle analysis demonstrated that cells co-expressing S37A β-catenin and MRJ(L) resulted in marked increase in S phase at 2 and 24 hours after the release of cell cycle block. The MRJ(L) expressors; did not go through an increase in the S phase in the 24 hour period after the release. Analysis of tumor growth in vivo (xenograft model) revealed that S37A β-catenin was able to restore the malignant activity overriding the suppressive effect of MRJ(L). Thus controlled degradation of β-catenin, brought about by MRJ(L), is an important event in maintaining cells in a non-tumorigenic state. Acknowledgement: We acknowledge grant support from the NCI: 1R01CA140472 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 997. doi:10.1158/1538-7445.AM2011-997
Cellular basis of insulin insensitivity in large rat adipocytes.
Authors: M P Czech
Journal: Journal of Clinical Investigation (1976)

The marked stimulatory effect of insulin on the conversion of 20 mM D-[6-14C]glucose to CO2, glyceride-glycerol, and fatty acid observed in small rat adipocytes was greatly diminished in large cells from older rats. Similarly, total glucose utilization as estimated by summing the total metabolites accumulated intracellularly plus the release of labeled CO2 and lactate was substantially lower in large cells in the presence of insulin and 5 mM labeled glucose. However, under conditions of 0.2 mM medium glucose where transport of the hexose into adipocytes is relatively more rate-limiting for subsequent metabolism, large cells actually utilized slightly greater total amounts of glucose than small cells in the presence of insulin. Increments of total glucose utilization due to both submaximal and maximal doses of insulin were similar in large and small cells incubated with a low glucose concentration. Under these conditions, conversion of labeled glucose to CO2 and fatty acid in response to insulin was somewhat diminished in large cells, while conversion to glyceride-glycerol was enhanced. The activity of the D-glucose transport system in large and small cells was estimated by monitoring initial rates and small cells was estimated by monitoring initial rates of 3-O-[3H]methylglucose uptake by a rapid filtration method. Transport system activity on a per cell basis was actually severalfold higher in large adipocytes in the basal state as well as in the presence of submaximal and maximal concentrations of insulin compared to small cells. However, the percent stimulation by insulin was less in the large cells. Uptake of 2-deoxyglucose under basal conditions and in response to insulin was also higher in large cells compared to small cells. Analysis of the accumulated label in extracts from fat cells incubated with D-[14C]deoxyglucose revealed the presence of free deoxyglucose, deoxyglucose-6-phosphate, and 6-phosphodeoxygluconate. The levels of these metabolites were significantly higher in large cells compared to small cells indicating hexokinase activity appears not to account for the defective glucose utilization in large cells at high glucose concentrations. It is concluded that (a) possible defects in insulin receptor components, the D-glucose transport system, and the coupling mechanism which links these entities do not significantly contribute to the apparent insulin-insensitivity of large fat cells and (b) the principal cellular defect which confers this blunted insulin response to large rat adipocytes involves one or more intracellular enzymes involved in glucose metabolism.
Abstract 3208: Impact of targeted therapy on circulating tumor cells in metastatic breast cancer treated by first-line chemotherapy: IC 2006-04 study
Authors: Jean-Yves Pierga, David Hajage, Thomas Bachelot, Suzette Delaloge, Etienne Brain, Mario Campone, Bernard Asselain, Claire Mathiot, François-Clément Bidard
Journal: Cancer Research (2011)

Abstract Circulating tumor cells (CTC) have been reported to be a prognostic marker in metastatic breast cancer. This study was designed to test whether changes in CTC counts during treatment are associated with outcome of first-line chemotherapy with/without targeted therapy. Methods: CTC were counted (CellSearch®) at baseline, before cycle 2 (C2) and C3/4 in 267 metastatic breast cancer patients. Usual prognostic variables, serum tumor markers, tumor response according to RECIST criteria and events were prospectively registered and compared with CTC status and outcome over time. Results: Median follow-up was 16 months, 45 patients (17%) had HER2 positive tumor and received trastuzumab, 55 (21%) had triple negative tumor, 125 received bevacizumab associated with CT. Baseline CTC positivity (65%; ≥1CTC/7.5ml threshold, 45% ≥5CTC/7.5ml threshold) was correlated with tumour markers, bone/liver involvement and number of metastatic sites, as well as performance status but was not statistically different according to breast cancer subtypes (hormone-positive, HER2-positive or triple-negative). At multivariate analysis, CTC ≥5CTC/7.5ml was an independent prognostic factor for progression-free survival (PFS), RR=1.9 (CI95% 1.26-2.88), p=0.002, with triple negative status, poor performance status and elevated CEA. For overall survival, CTC ≥5CTC/7.5ml was an independent prognostic factor with triple negative status and poor performance status (RR=2.41, p=0.02). Changes with a threshold ≥5CTC/7.5ml, between baseline and Cycle 2 were highly correlated with both PFS (p=5e-07) and OS (p=3e-07). Persistent CTC positivity at C2 was associated with lower tumor response (p=4e-03). Among CTC-positive patients at baseline treated by chemotherapy only, chemotherapy/bevacizumab and chemotherapy/anti-HER2, CTC counts decreased respectively below the ≥5CTC/7.5ml positivity threshold before cycle 2 in 53%, 64% and 83% of patients, and before cycle 3 or 4, in 62%, 77% and 100% of patients (p=0.04). Prognostic value of CTC count at baseline and C2 remained in all subgroups. Conclusions: CTC count appeared to decrease more markedly in the patients who received also bevacizumab or trastuzumab. However, CTC remain a reliable independent prognostic marker in metastatic breast cancer treated by first-line chemotherapy with/without targeted therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3208. doi:10.1158/1538-7445.AM2011-3208
The “mesh” as evidence – model comparison and alternative interpretations of feedback
Authors: Oliver J. Hulme, Louise Whiteley
Journal: Behavioral and Brain Sciences (2007)

Abstract We agree that the relationship between phenomenology and accessibility can be fruitfully investigated via meshing, but we want to emphasise the importance of proper comparison between meshes, as well as considerations that make comparison especially difficult in this domain. We also argue that Block's interpretation of the neural data in his exemplar mesh is incorrect, and propose an alternative.