tbuckley/cabot-search huggingface dataset:
The hibernators heart Nature's response to arrhythmogenesis?
Authors: T Opthof
Journal: Cardiovascular Research (2000)

See article by Saitongdee et al. [1] (pages 108–115) in this issue. 

In this issue, Saitongdee et al. [1] describe an increase in connexin43, the major constituent of gap junctions in ventricular muscle [2], in hamsters ( Mesocricetus auratus ) exposed to circumstances that provoke hibernation of the animals. The hamsters were subjected to a temperature of 5°C in combination with 2 h of light per 24 h during a period of 8–10 weeks after a gradual transition from normal conditions to hypothermia. During control conditions the temperature was 20°C with a 8:16-h light/dark circadian photoperiod. Reduction of temperature and light period was 1°C and 30 min per day, respectively. This procedure led to the induction of hibernation in some, but not all animals. The latter were considered cold controls. Interestingly, the area density of connexin43 was 2.5 times as large in hibernators compared with controls (deduced from Fig. 2 in Ref. [1]) with the ‘cold controls’ in between. Both the number and the dimensions of the gap junctions increased. The increase in connexin43 was not only observed in the animals that actually hibernated, but also in the animals that did not, despite the presence of identical environmental stimuli. This suggests that the environmental stimuli and not primarily the body temperature (which was 5°C in hibernating animals and normal in ‘cold controls’) cause the increase in connexin43. Arousal, which is the biological term … 

* Corresponding author. Tel.: +31-30-253-8900; fax: +31-30-253-9036 t.opthof{at}med.uu.nl
FURTHER REPORT ON NURSES' CONDUCT SCHEME
Authors: James S. Plant
Journal: American Journal of Psychiatry (1923)

This nurses' conduct scheme has continued in successful operation for the year. It has been successful fundamentally because it challenges the nurses' cooperation in the research work of the hospital. It has been favorably accepted elsewhere, though on a much smaller, scale than that which we are carrying out here. This scheme represents an attempt at a mathematical evaluation of the clinical condition of the patient and were there the space to publish all of the charts we could establish our contention—that even in its present crude form, this scheme gives a picture more accurate and more helpful than any hitherto made of the clinical progress of psychotic cases. As a clinical correlate for recurrent laboratory procedures some such scheme is a necessity and this scheme represents, to date, at least a hopeful answer to this need. Such a scheme must have a rational basis. Our own method of meeting this requirement has been described, partly as a history of its progress and partly as some sort of a map for the future construction of such rating schemes. We have challenged, on the basis of results, the unquestioned acceptance of Binet's doctrine of sampling. There are now something over 70,000 entries. It seems that this represents, at least in these early states of the scheme, a sufficient amount of data on which to go ahead. Again I must make my acknowledgments to the nurses of McLean Hospital. Theirs has been a loyalty and interest without which we could never have hoped to embark upon this experimental phase of the scheme. Without their cooperation and helpful criticism we could have gotten nowhere. Again, my wife, through suggestions and constant assistance has assured the progress of the present year.
Results of the Intergroup Rhabdomyosarcoma Study Group D9602 Protocol, Using Vincristine and Dactinomycin With or Without Cyclophosphamide and Radiation Therapy, for Newly Diagnosed Patients With Low-Risk Embryonal Rhabdomyosarcoma: A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group
Authors: R. Beverly Raney, David O. Walterhouse, Jane L. Meza, Richard J. Andrassy, John C. Breneman, William M. Crist, Harold M. Maurer, William H. Meyer, David M. Parham, James R. Anderson
Journal: Journal of Clinical Oncology (2011)

Patients with localized, grossly resected, or gross residual (orbital only) embryonal rhabdomyosarcoma (ERMS) had 5-year failure-free survival (FFS) rates of 83% and overall survival rates of 95% on Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols III/IV. IRSG D9602 protocol (1997 to 2004) objectives were to decrease toxicity in similar patients by reducing radiotherapy (RT) doses and eliminating cyclophosphamide for the lowest-risk patients.Subgroup A patients (lowest risk, with ERMS, stage 1 group I/IIA, stage 1 group III orbit, stage 2 group I) received vincristine plus dactinomycin (VA). Subgroup B patients (ERMS, stage 1 group IIB/C, stage I group III nonorbit, stage 2 group II, stage 3 group I/II) received VA plus cyclophosphamide. Patients in group II/III received RT. Compared with IRS-IV, doses were reduced from 41.4 to 36 Gy for stage 1 group IIA patients and from 50 or 59 to 45 Gy for group III orbit patients.Estimated 5-year FFS rates were 89% (95% CI, 84% to 92%) for subgroup A patients (n = 264) and 85% (95% CI, 74%, 91%) for subgroup B patients (n = 78); median follow-up: 5.1 years. Estimated 5-year FFS rates were 81% (95% CI, 68% to 90%) for patients with stage 1 group IIA tumors (n = 62) and 86% (95% CI, 76% to 92%) for patients with group III orbit tumors (n = 77).Five-year FFS and OS rates were similar to those observed in comparable IRS-III patients, including patients receiving reduced RT doses, but were lower than in comparable IRS-IV patients receiving VA plus cyclophosphamide. Five-year FFS rates were similar among subgroups A and B patients.
Calmodulin Kinase Inhibition Prevents Development of the Arrhythmogenic Transient Inward Current
Authors: Yuejin Wu, Dan M. Roden, Mark E. Anderson
Journal: Circulation Research (1999)

Although it is widely accepted that afterdepolarizations initiate arrhythmias when action potentials are prolonged, the underlying mechanisms are unclear. In this study, we tested the hypothesis that action potential prolongation would raise intracellular calcium and thereby activate the arrhythmogenic transient inward current (Iti). Furthermore, given that Iti can be activated by sarcoplasmic reticulum Ca2+ release, we tested the hypothesis that inhibition of calmodulin (CaM) kinase would prevent Iti. Isolated rabbit ventricular myocytes were studied with whole-cell-mode voltage clamp. Stimulation with a prolonged action potential clamp, under near-physiological conditions, increased [Ca2+]i. Iti was reproducibly induced in 60 of 60 cells, but Iti was not seen with the use of a shorter action potential waveform (n=12). Iti was associated with a secondary elevation in [Ca2+]i. When [Ca2+]i buffering was enhanced by dialysis with BAPTA (20 mmol/L, n=9), no Iti was present. The Na+/Ca2+ exchanger was likely responsible for Iti, because Iti was inhibited by the Na+/Ca2+ exchanger inhibitory peptide XIP (10 micromol/L, n=6), but not by an inactive scrambled peptide (10 micromol/L, n=5) or by the Cl- current antagonist niflumic acid (10 to 40 micromol/L, n=9). Activator Ca2+ from the sarcoplasmic reticulum was essential for development of Iti, because it was prevented by pretreatment with ryanodine (10 micromol/L, n=6) or thapsigargin (1 micromol/L, n=6). Two different CaM kinase inhibitory peptides (n=16) and a CaM inhibitory peptide (n=4) completely suppressed Iti. These results are consistent with the hypothesis that CaM kinase plays a role in arrhythmias related to increased [Ca2+]i.
Role of Isolated Locoregional Recurrence of Breast Cancer: Results of Four Prospective Studies
Authors: Claudia Schmoor, Willi Sauerbrei, Gunter Bastert, Martin Schumacher
Journal: Journal of Clinical Oncology (2000)

PURPOSE: We evaluated the effect on future prognosis of an isolated locoregional recurrence (ILRR) after the primary diagnosis of breast cancer. Using data from four prospective studies of the German Breast Cancer Study Group, we investigated factors influencing prognosis after ILRR and defined a simple classification of patients into groups with different prognoses. PATIENTS AND METHODS: From 1983 to 1989, 2,746 patients were recruited into four studies comparing different treatments in primary breast cancer. After a median follow-up time of 8 years, 337 patients developed an ILRR as the first event. The influence of ILRRs on disease progression was examined. The effects of different prognostic factors on progression-free survival (PFS) and overall survival after ILRR were analyzed after a median follow-up time of 4.5 years. RESULTS: ILRRs increased the risk with respect to distant recurrence and death. After ILRR, 185 events occurred with respect to the PFS end point, and 171 patients died. Primary nodal status, tumor grade, estrogen receptor status of the primary tumor, and length of the disease-free interval (DFI) until the time of the ILRR had a significant prognostic impact. CONCLUSION: Determinants of prognosis after the ILRR should be taken into account for designing future risk-adapted clinical studies for these patients. Risk strata can be defined by a simple classification scheme based on primary nodal status and DFI.
Toxicology of Hydrogen Sulfide
Authors: R J Reiffenstein, W C Hulbert, S H Roth
Journal: The Annual Review of Pharmacology and Toxicology (1992)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Digoxin- and digitoxin-induced changes in monophasic action potential of the right ventricle of the dog heart
Authors: J. P AMLIE, L. STORSTEIN, H. WATANABE
Journal: Cardiovascular Research (1980)

The effects of digitoxin and digoxin on right ventricular monophasic action potentials were studied in intact dogs during an 8 hour observation period. Pentobarbital anaesthesia was used, and monophasic action potential recordings were obtained with the suction electrode technique. Intravenous injection of 2.0 mg digitoxin to six dogs, 2.0 mg digoxin to two dogs and 1.0 mg digoxin to five dogs caused a rapid increase in the time taken for 90% repolarisation with return to control values after 20 to 30 min. A late increase in 50 and 90% repolarisation times was observed 2 to 4 h after digitoxin, while digoxin had no such effect. The late action potential prolonging effect was inversely correlated to serum concentrations in the early elimination phase (2 to 8 h after the injection) since it reached a maximum towards the end of the observation period. Digitoxin and digoxin thus differed in their late effects on ventricular monophasic action potentials in intact dogs and may possess different antiarrhythmic activity.
A successful renal transplantation in Behcet's syndrome
Authors: S. APAYDIN, E. EREK, U. ULKU, V. HAMURYUDAN, H. YAZICI, M. SARIYAR
Journal: Annals of the Rheumatic Diseases (1999)

Renal involvement is not frequent in Behcet’s syndrome (BS) and consists of occasional reports of patients having glomerulonephritis,1 IgA nephropathy2 and renal amyloidosis.3 We present the successful outcome of a renal transplantation in a patient who had end stage renal failure secondary to glomerulonephritis. To our knowledge, this is the first patient with BS to receive an organ transplantation.

The detailed history of this patient at the time of the diagnosis of glomerulonephritis was the subject of a case report in 1991.4 In brief, she was 21 years old when she developed recurrent oral and genital ulcers, bilateral uveitis, erythema nodosum, folliculitis, and intermittent arthritis of the knees. Two years later, she was referred to our centre for further evaluation of eye symptoms. She …
5-HT Receptor Regulation of Neurotransmitter Release
Authors: Klaus B. Fink, Manfred Göthert
Journal: Pharmacological Reviews (2007)

Serotoninergic neurons in the central nervous system impinge on many other neurons and modulate their neurotransmitter release. This review focuses on 1) the function of presynaptic 5-hydroxytryptamine (5-HT) heteroreceptors on axon terminals of central cholinergic, dopaminergic, noradrenergic, or GABAergic neurons and 2) the role of GABAergic interneurons expressing 5-HT heteroreceptors in the regulation of acetylcholine, dopamine, or noradrenaline release. In vitro studies on slices or synaptosomes and in vivo microdialysis experiments have shown that 5-HT<sub>1A</sub>, 5-HT<sub>1B</sub>, 5-HT<sub>2A</sub>, 5-HT<sub>2C</sub>, 5-HT<sub>3</sub>, and/or 5-HT<sub>4</sub> heteroreceptors mediate this modulation. 5-HT<sub>1B</sub> receptors on neocortical cholinergic, striatal dopaminergic, or hippocampal GABAergic axon terminals are examples for release-inhibiting 5-HT heteroreceptors; 5-HT<sub>3</sub> receptors on hippocampal GABAergic or 5-HT<sub>4</sub> receptors on hippocampal cholinergic axon terminals are examples for release-facilitating 5-HT heteroreceptors. GABA released from GABAergic interneurons upon activation of facilitatory 5-HT receptors, e.g., 5-HT<sub>2A</sub> or 5-HT<sub>3</sub> receptors, mediates inhibition of the release of other neurotransmitters such as prefrontal neocortical dopamine or neocortical acetylcholine release, respectively. Conversely, attenuated GABA release in response to activation of inhibitory 5-HT heteroreceptors, e.g., 5-HT<sub>1A</sub> or 5-HT<sub>1B</sub> receptors on GABAergic interneurons is involved in paradoxical facilitation of hippocampal acetylcholine and striatal dopamine release, respectively. Such 5-HT heteroreceptors are considered potential targets for appropriate 5-HT receptor ligands which, by enhancing the release of a relevant neurotransmitter, can compensate for its hypothesized deficiency in distinct brain areas. Examples for such deficiencies are the impaired release of hippocampal or neocortical acetylcholine, striatal dopamine, and hippocampal or neocortical noradrenaline in disorders such as Alzheimer9s disease, Parkinson9s disease, and major depression, respectively.
Genetically Engineered Microvesicles Carrying Suicide mRNA/Protein Inhibit Schwannoma Tumor Growth
Authors: Arda Mizrak, Mehmet Fatih Bolukbasi, Gokhan Baris Ozdener, Gary J Brenner, Sibylle Madlener, Erdogan Pekcan Erkan, Thomas Ströbel, Xandra O Breakefield, Okay Saydam
Journal: Molecular Therapy (2012)

Microvesicles (MVs) play an important role in intercellular communication by carrying mRNAs, microRNAs (miRNAs), non-coding RNAs, proteins, and DNA from cell to cell. To our knowledge, this is the first report of delivery of a therapeutic mRNA/protein via MVs for treatment of cancer. We first generated genetically engineered MVs by expressing high levels of the suicide gene mRNA and protein-cytosine deaminase (CD) fused to uracil phosphoribosyltransferase (UPRT) in MV donor cells. MVs were isolated from these cells and used to treat pre-established nerve sheath tumors (schwannomas) in an orthotopic mouse model. We demonstrated that MV-mediated delivery of CD-UPRT mRNA/protein by direct injection into schwannomas led to regression of these tumors upon systemic treatment with the prodrug (5-fluorocytosine (5-FC)), which is converted within tumor cells to 5-fluorouracil (5-FU)-an anticancer agent. Taken together, these studies suggest that MVs can serve as novel cell-derived "liposomes" to effectively deliver therapeutic mRNA/proteins to treatment of diseases.
Characterization of murine lung dendritic cells: similarities to Langerhans cells and thymic dendritic cells.
Authors: A M Pollard, M F Lipscomb
Journal: The Journal of Experimental Medicine (1990)

Dendritic cells (DC) are potent accessory cells (AC) for the initiation of primary immune responses. Although murine lymphoid DC and Langerhans cells have been extensively characterized, DC from murine lung have been incompletely described. We isolated cells from enzyme-digested murine lungs and bronchoalveolar lavages that were potent stimulators of a primary mixed lymphocyte response (MLR). The AC had a low buoyant density, were loosely adherent and nonphagocytic. AC function was unaffected by depletion of cells expressing the splenic DC marker, 33D1. In addition, antibody and complement depletion of cells bearing the macrophage marker F4/80, or removal of phagocytic cells with silica also failed to decrease AC activity. In contrast, AC function was decreased by depletion of cells expressing the markers J11d and the low affinity interleukin 2 receptor (IL-2R), both present on thymic and skin DC. AC function was approximately equal in FcR+ and FcR- subpopulations, indicating there was heterogeneity within the AC population. Consistent with the functional data, a combined two-color immunofluorescence and latex bead uptake technique revealed that lung cells high in AC activity were enriched in brightly Ia+ dendritic-shaped cells that (a) were nonphagocytic, (b) lacked specific T and B lymphocyte markers and the macrophage marker F4/80, but (c) frequently expressed C3biR, low affinity IL-2R, FcRII, and the markers NLDC-145 and J11d. Taken together, the functional and phenotypic data suggest the lung cells that stimulate resting T cells in an MLR and that might be important in local pulmonary immune responses are DC that bear functional and phenotypic similarity to other tissues DC, such as Langerhans cells and thymic DC.
Treatment of Hypertension in Patients 80 Years of Age or Older
Authors: Nigel S. Beckett, Ruth Peters, Astrid E. Fletcher, Jan A. Staessen, Lisheng Liu, Dan Dumitrascu, Vassil Stoyanovsky, Riitta L. Antikainen, Yuri Nikitin, Craig Anderson, Alli Belhani, Françoise Forette, Chakravarthi Rajkumar, Lutgarde Thijs, Winston Banya, Christopher J. Bulpitt
Journal: New England Journal of Medicine (2008)

Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death.We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting-enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke.The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], -1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, -1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001).The results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT00122811 [ClinicalTrials.gov].).
Weight faltering and failure to thrive in infancy and early childhood
Authors: B. Shields, I. Wacogne, C. M. Wright
Journal: BMJ (2012)

Weight faltering, or failure to thrive, is a childhood condition that provokes concern about possible neglect, deprivation, and organic illness.However, research over the past 20 years has brought the validity of this concern into question, leading to the proposal that management should be less aggressive. 1 We summarise the evidence base, discuss new developments, and provide a practical approach to management.Failure to thrive has been defined in a range of ways, with no overall accepted definition 2 but an essential element is subnormal growth or weight gain, hence the increasing use in recent years of the term weight faltering.
An anthropological approach to the evaluation of preschool children exposed to pesticides in Mexico.
Authors: E A Guillette, M M Meza, M G Aquilar, A D Soto, I E Garcia
Journal: Environmental Health Perspectives (1998)

In this comparative study, we compensated for many of the known variables that influence children's growth and development by selecting two groups of 4-5-year-old Yaqui children who reside in the Yaqui Valley of northwestern Mexico. These children share similar genetic backgrounds, diets, water mineral contents, cultural patterns, and social behaviors. The major difference was their exposure to pesticides. Pesticides have been applied to the agricultural area of the valley since the late 1940s. In 1990, high levels of multiple pesticides were found in the cord blood of newborns and in breast milk. Building on anthropological methods for rapid rural appraisal of problems within the environment, a Rapid Assessment Tool for Preschool Children (RATPC) was developed to measure growth and development. The children of the agrarian region were compared to children living in the foothills, where pesticide use is avoided. The RATPC measured varied aspects of physical growth and abilities to perform, or function in, normal childhood activities. No differences were found in growth patterns. Functionally, the exposed children demonstrated decreases in stamina, gross and fine eye-hand coordination, 30-minute memory, and the ability to draw a person. The RATPC also pointed out areas in which more in-depth research on the toxicology of pesticides would be valuable.
Determining levels of physical activity in attending physicians, resident and fellow physicians and medical students in the USA
Authors: Fatima Cody Stanford, Martin W Durkin, Steven N Blair, Caroline Keller Powell, Mary Beth Poston, James Rast Stallworth
Journal: British Journal of Sports Medicine (2011)

Objective Evidence suggests that the level of physical activity of physicians can be correlated directly with physician counselling patterns about this behaviour. Our objective was to determine if medical students, resident and fellow physicians and attending physicians meet the physical activity guidelines set forth by the US Department of Health and Human Services. Methods A representative cross-sectional web-based survey was conducted in June 2009–January 2010 throughout the USA (N=1949). Using the short form of the International Physical Activity Questionnaire, the authors gathered demographical data and information related to physical activity, the level of training, the number of work hours per week, body mass index (BMI), confidence about counselling about physical activity and frequency with which the physical activity is encouraged to his/her patients. Results Based on the 1949 respondents, attending physicians (84.8%) and medical students (84%) were more likely than resident (73.2%) and fellow physicians (67.9%) to meet physical activity guidelines. Conclusion Physicians and medical students engage in more physical activity and tend to have a lower BMI than the general population. Resident and fellow physicians engage in less physical activity than attending physicians and medical students.