tbuckley/cabot-search huggingface dataset:
Post-Countershock Arrhythmias in Untreated and Digitalized Dogs
Authors: ROBERT E. TEN EICK, STEVEN R. WYTE, SAMUEL M. ROSS, BRIAN F. HOFFMAN
Journal: Circulation Research (1967)

Recent studies suggest that countershock can stimulate cardiac autonomic nerves and that the resulting release of norepinephrine contributes to post-countershock (PCS) arrhythmias. β-Adrenergic receptor blocking agents, reserpine, cocaine, and cardiac-denervated preparations were used to evaluate this hypothesis in dogs under pentobarbital anesthesia. The suitability of the dog as an experimental system was examined. In the normal dog, the duration of PCS arrhythmia caused by a countershock of given energy was increased 100% by ouabain (0.05 mg/kg iv). In both normal dogs and dogs given ouabain (0.05 mg/kg iv), dichloroisoproterenol, pronethalol, and propranolol reduced the duration of PCS arrhythmia; reserpine, a norepinephrine depletor, reduced the duration of PCS arrhythmia; cocaine, a norepinephrine-uptake inhibitor possessing antiarrhythmic properties, increased the duration of PCS arrhythmia; denervation of the heart reduced the duration of PCS arrhythmia. Ouabain (0.05 mg/kg iv) reduced the duration of PCS arrhythmia in dogs with denervated hearts. These findings indicate that PCS arrhythmia in dogs is norepinephrine dependent. Evidence indicated that ouabain has an anti-adrenergic action on the heart also is presented.
Glioma is formed by active Akt1 alone and promoted by active Rac1 in transgenic zebrafish
Authors: In Hye Jung, Ga Lam Leem, Dawoon E. Jung, Min Hee Kim, Eun Young Kim, Se Hoon Kim, Hae-Chul Park, Seung Woo Park
Journal: Neuro-Oncology (2013)

Ongoing characterization of glioma has revealed that Akt signaling plays a crucial role in gliomagenesis. In mouse models, however, Akt alone was not sufficient to induce glioma. We established transgenic zebrafish that overexpressed dominant-active (DA) human Akt1 or Rac1G12V (DARac1) at ptf1a domain and investigated transgenic phenotypes and mechanisms leading to gliomagenesis. Transgene expressions were spatiotemporally restricted without any developmental abnormality of embryos and persisted at cerebellum and medulla in adult zebrafish. DAAkt1 alone induced glioma (with visible bumps at the head), with incidences of 36.6% and 49% at 6 and 9 months, respectively. Histologically, gliomas showed various histologic grades, increased proliferation, and frequent invasion into the fourth ventricle. Preferential location of small tumors at periventricular area and coexpression of Her4 suggested that tumors originated from Ptf1a- and Her4-positive progenitor cells at ventricular zone. Gliomagenesis was principally mediated by activation of survival pathway through upregulation of survivin genes. Although DARac1 alone was incapable of gliomagenesis, when coexpressed with DAAkt1, gliomagenesis was accelerated, showing higher tumor incidences (62.0% and 73.3% at 6 and 9 months, respectively), advanced histologic grade, invasiveness, and shortened survival. DARac1 upregulated survivin2, cyclin D1, β-catenin, and snail1a but downregulated E-cadherin, indicating that DARac1 promotes gliomagenesis by enhancing proliferation, survival, and epithelial-to-mesenchymal transition. On pharmacologic tests, only Akt1/2 inhibitor effectively suppressed gliomagenesis, inhibited cellular proliferation, and induced apoptosis in established gliomas. The zebrafish model reinforces the pivotal role of Akt signaling in gliomagenesis and suggests Rac1 as an important protein involved in progression.
Options for fertility preservation in prepubertal boys
Authors: C. Wyns, M. Curaba, B. Vanabelle, A. Van Langendonckt, J. Donnez
Journal: Human Reproduction Update (2010)

BACKGROUNDFertility in adult life may be severely impaired by gonadotoxic therapies. For young boys who do not yet produce spermatozoa, cryopreservation of immature testicular tissue (ITT) is an option to preserve their fertility, albeit still experimental. This paper covers current options for ITT cryopreservation and fertility restoration.
Enhancement of Osteoclastic Bone Resorption and Suppression of Osteoblastic Bone Formation in Response to Reduced Mechanical Stress Do Not Occur in the Absence of Osteopontin
Authors: Muneaki Ishijima, Susan R. Rittling, Teruhito Yamashita, Kunikazu Tsuji, Hisashi Kurosawa, Akira Nifuji, David T. Denhardt, Masaki Noda
Journal: The Journal of Experimental Medicine (2001)

Reduced mechanical stress to bone in bedridden patients and astronauts leads to bone loss and increase in fracture risk which is one of the major medical and health issues in modern aging society and space medicine. However, no molecule involved in the mechanisms underlying this phenomenon has been identified to date. Osteopontin (OPN) is one of the major noncollagenous proteins in bone matrix, but its function in mediating physical-force effects on bone in vivo has not been known. To investigate the possible requirement for OPN in the transduction of mechanical signaling in bone metabolism in vivo, we examined the effect of unloading on the bones of OPN−/− mice using a tail suspension model. In contrast to the tail suspension–induced bone loss in wild-type mice, OPN−/− mice did not lose bone. Elevation of urinary deoxypyridinoline levels due to unloading was observed in wild-type but not in OPN−/− mice. Analysis of the mechanisms of OPN deficiency–dependent reduction in bone on the cellular basis resulted in two unexpected findings. First, osteoclasts, which were increased by unloading in wild-type mice, were not increased by tail suspension in OPN−/− mice. Second, measures of osteoblastic bone formation, which were decreased in wild-type mice by unloading, were not altered in OPN−/− mice. These observations indicate that the presence of OPN is a prerequisite for the activation of osteoclastic bone resorption and for the reduction in osteoblastic bone formation in unloaded mice. Thus, OPN is a molecule required for the bone loss induced by mechanical stress that regulates the functions of osteoblasts and osteoclasts.
Identification of Two New Mutations in the Glucokinase Gene That Result in Maturity-Onset Diabetes of the Young
Authors: Seth D. Marks, Robert M. Couch
Journal: Diabetes Care (2010)

Glucokinase catalyzes glucose to glucose-6-phosphate conversion in the pancreatic β-cell and is a key regulator of insulin secretion (1). The glucokinase gene ( GCK ) on chromosome 7p15.3–15.1 has 12 exons. GCK heterozygous inactivating mutations result in mild fasting hyperglycemia termed maturity-onset diabetes of the young type 2 (MODY2) or MODY-GCK (MIM # 125851) (2). The mutations result in diminished insulin secretion (3) and possibly decreased hepatic glucose uptake and glycogen synthesis (4). Several hundred inactivating mutations throughout exons 2 to 10 have been described (5). We report two previously undescribed mutations.

Both patients were assessed at the Pediatric Diabetes Education Centre, Stollery Children's Hospital, Edmonton, Canada. Glucose and A1C …
Bilateral diagnostic thoracocentesis may not be routinely indicated in patients with bilateral pleural effusion
Authors: K Mohan
Journal: Thorax (2004)

▴ Kalomenidis I, Rodriguez M, Barnette M, et al . Patients with bilateral pleural effusion are the findings the same in each fluid Chest2003124167–76

[OpenUrl][1][CrossRef][2][PubMed][3]



Bilateral pleural effusion is a common clinical finding with an incidence of 1535 in patients with pleural effusion or on intensive care units. Congestive cardiac failure and neoplastic pleural effusion remain the common causes of bilateral pleural effusions.

In this pilot study, cellular red blood …

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Early Telomere Shortening and Genomic Instability in Tubo-Ovarian Preneoplastic Lesions—Letter
Authors: Haifeng Qiu
Journal: Clinical Cancer Research (2013)

In a recent article, Chene and colleagues reported that telomere length shortened gradually when comparing tubo-ovarian dysplasia with serous tubal intraepithelial carcinoma, and shorter telomere length was associated with BRCA1/2 mutations (1). However, we have several concerns in regards to these findings.First, it is well known that telomere length is inversely correlated with increasing age in both healthy and cancer populations (2, 3). In addition, estrogen deficiency has been found to decrease telomerase activity and shorten telomere length in the ovary of mice (4). Unfortunately, no information about age or menopausal status was supplied in the present study.Second, telomere length has been previously investigated in a panel of 178 sporadic and 168 hereditary ovarian cancer cases (5). Both sporadic and hereditary ovarian cancers exhibited showed shorter telomeres than the age-matched normal controls and even much shorter telomeres were found in the BRCA1/2 mutation carriers. Interestingly, Chene and colleagues mention that the telomeres of patients with cancer were longer than those in the dysplasia cases. Given that BRCA1/2 status was not provided for the cancer group, we wonder whether this is just a bias caused by a different incidence of BRCA1/2 mutations?In summary, we suggest that age and menopausal status should be taken into considerations for this study and that BRCA1/2 mutation status in both the control and cancer groups needs to be clarified.See the Response, p. 5255No potential conflicts of interest were disclosed.
Multifocal and Multicentric Breast Cancer: Does Each Focus Matter?
Authors: Nathan J. Coombs, John Boyages
Journal: Journal of Clinical Oncology (2005)

The identification of multiple tumors in the breast is associated with increased nodal involvement when compared with similar staged unifocal disease. This study compares two methods of tumor size assessment to predict tumor behavior in the relationship between size and axillary node involvement for patients with multifocal and multicentric breast cancer.The histologic reports of every patient with multifocal breast cancer treated in New South Wales between April 1995 and September 1995 were examined. Tumors were assessed using two size estimates: (1) largest tumor focus diameter and (2) the aggregate diameters of all tumor foci. The dimensions were compared with unifocal tumors and against node positivity.Ninety-four (11.1%) of 848 women had multifocal breast cancer and of these 49 women (52.1%) had axillary node involvement compared with 37.5% with unifocal breast cancer (P =.007). The use of aggregate dimension reclassified significant numbers of multifocal tumors at a more advanced stage. Use of this method to stage cancers, rather than the largest tumor size, removed the excess node positivity when compared with unifocal, stage-matched breast carcinomas.The tendency of breast tumors to metastasize is a reflection of the total tumor load. Failure to measure the additional tumor burden provided by multiple small foci may understage a woman's disease. This may deny patients the opportunity of adjuvant therapies if the contribution of the smaller foci to the incidence of node positivity and survival is ignored.
<b>BMP4 Promotes Prostate Tumor Growth in Bone through Osteogenesis</b>
Authors: Yu-Chen Lee, Chien-Jui Cheng, Mehmet A. Bilen, Jing-Fang Lu, Robert L. Satcher, Li-Yuan Yu-Lee, Gary E. Gallick, Sankar N. Maity, Sue-Hwa Lin
Journal: Cancer Research (2011)

Induction of new bone formation is frequently seen in the bone lesions from prostate cancer. However, whether osteogenesis is necessary for prostate tumor growth in bone is unknown. Recently, 2 xenografts, MDA-PCa-118b and MDA-PCa-133, were generated from prostate cancer bone metastases. When implanted subcutaneously in severe combined immunodeficient (SCID) mice, MDA-PCa-118b induced strong ectopic bone formation while MDA-PCa-133 did not. To identify the factors that are involved in bone formation, we compared the expression of secreted factors (secretome) from MDA-PCa-118b and MDA-PCa-133 by cytokine array. We found that the osteogenic MDA-PCa-118b xenograft expressed higher levels of bone morphogenetic protein BMP4 and several cytokines including interleukin-8, growth-related protein (GRO), and CCL2. We showed that BMP4 secreted from MDA-PCa-118b contributed to about a third of the osteogenic differentiation seen in MDA-PCa-118b tumors. The conditioned media from MDA-PCa-118b induced a higher level of osteoblast differentiation, which was significantly reduced by treatment with BMP4 neutralizing antibody or the small molecule BMP receptor 1 inhibitor LDN-193189. BMP4 did not elicit an autocrine effect on MDA-PCa-118b, which expressed low to undetectable levels of BMP receptors. Treatment of SCID mice bearing MDA-PCa-118b tumors with LDN-193189 significantly reduced tumor growth. Thus, these studies support a role of BMP4-mediated osteogenesis in the progression of prostate cancer in bone.
Endogenous Nitric Oxide and Myocardial Adaptation to Ischemia
Authors: Gerd Heusch, Heiner Post, Martin C. Michel, Malte Kelm, Rainer Schulz
Journal: Circulation Research (2000)

Abstract —Ischemic myocardium does not inevitably undergo necrosis but rather can survive through downregulation of contractile function, ie, “hibernate.” To study the role of endogenous NO in this adaptation, 41 enflurane-anesthetized swine were subjected to 90 minutes of moderate left anterior descending coronary artery hypoperfusion and assigned to placebo (P), to 30 mg/kg N G -nitro- l -arginine (L-NNA) IV to inhibit NO synthase, or to aortic constriction (AO) to match the increased left ventricular pressure observed with L-NNA. During normoperfusion, a regional myocardial external work index (WI, mm Hg · mm, sonomicrometry and micromanometry) was reduced with L-NNA (from 326±27 [SEM] to 250±19, P &lt;0.05) but increased with AO (from 321±16 to 363±19, P &lt;0.05 versus L-NNA). At 10 minutes of ischemia, WI was lower with L-NNA (109±10, P &lt;0.05) than P (180±22) and AO (170±11) and did not change further at 85 minutes of ischemia. Relationships between WI and transmural myocardial blood flow and oxygen consumption were shifted rightward by L-NNA versus P and AO at both 10 and 85 minutes of ischemia. The maximal increment in calcium-activated external work was not different during normoperfusion among groups but was decreased during ischemia with L-NNA. L-NNA transiently increased myocardial contractile calcium sensitivity along with systemic pressure but reduced it during ongoing ischemia. The free-energy change of ATP hydrolysis after an early ischemic decrease recovered toward baseline values in all groups, and necrosis was absent after 2 (triphenyltetrazolium chloride staining) or 8 (histology) hours of reperfusion. Thus, endogenous NO contributes to hibernation by reducing oxygen consumption and preserving calcium sensitivity and contractile function without an energy cost during ischemia. (Circ Res. 2000;87:146-152.)
Mammographic Breast Density and Breast Cancer: Evidence of a Shared Genetic Basis
Authors: Jajini S. Varghese, Deborah J. Thompson, Kyriaki Michailidou, Sara Lindström, Clare Turnbull, Judith Brown, Jean Leyland, Ruth M.L. Warren, Robert N. Luben, Ruth J. Loos, Nicholas J. Wareham, Johanna Rommens, Andrew D. Paterson, Lisa J. Martin, Celine M. Vachon, Christopher G. Scott, Elizabeth J. Atkinson, Fergus J. Couch, Carmel Apicella, Melissa C. Southey, Jennifer Stone, Jingmei Li, Louise Eriksson, Kamila Czene, Norman F. Boyd, Per Hall, John L. Hopper, Rulla M. Tamimi, Nazneen Rahman, Douglas F. Easton
Journal: Cancer Research (2012)

Abstract Percent mammographic breast density (PMD) is a strong heritable risk factor for breast cancer. However, the pathways through which this risk is mediated are still unclear. To explore whether PMD and breast cancer have a shared genetic basis, we identified genetic variants most strongly associated with PMD in a published meta-analysis of five genome-wide association studies (GWAS) and used these to construct risk scores for 3,628 breast cancer cases and 5,190 controls from the UK2 GWAS of breast cancer. The signed per-allele effect estimates of single-nucleotide polymorphisms (SNP) were multiplied with the respective allele counts in the individual and summed over all SNPs to derive the risk score for an individual. These scores were included as the exposure variable in a logistic regression model with breast cancer case–control status as the outcome. This analysis was repeated using 10 different cutoff points for the most significant density SNPs (1%–10% representing 5,222–50,899 SNPs). Permutation analysis was also conducted across all 10 cutoff points. The association between risk score and breast cancer was significant for all cutoff points from 3% to 10% of top density SNPs, being most significant for the 6% (2-sided P = 0.002) to 10% (P = 0.001) cutoff points (overall permutation P = 0.003). Women in the top 10% of the risk score distribution had a 31% increased risk of breast cancer [OR = 1.31; 95% confidence interval (CI), 1.08–1.59] compared with women in the bottom 10%. Together, our results show that PMD and breast cancer have a shared genetic basis that is mediated through a large number of common variants. Cancer Res; 72(6); 1478–84. ©2012 AACR.
Engineering and Material Considerations in Islet Cell Transplantation
Authors: Elliot L. Chaikof
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract The successful application and optimization of cell transplantation will require quantitative engineering design and analysis of cells and materials in which relevant biological processes remain complex and incompletely defined. This report primarily reviews the engineering and material considerations in islet cell transplantation, including established biological constraints and biohybrid devices for cell delivery, as well as available barrier materials and the associated processing strategies directed at the control of solute transport, barrier permeability, and host responses at the biological–material interface. Also described are current areas of investigation with particular promise as enabling technologies for accelerating the clinical effectiveness of islet cell transplantation.
Trends in Initial Lower Extremity Amputation Rates Among Veterans Health Administration Health Care System Users From 2000 to 2004
Authors: Chin-Lin Tseng, Mangala Rajan, Donald R. Miller, Jean-Philippe Lafrance, Leonard Pogach
Journal: Diabetes Care (2011)

To evaluate temporal trends in rates of initial lower extremity amputation (ILEA) among patients with diabetes in the Veterans Health Administration (VHA).Retrospective administrative data analysis of VHA clinic users with diabetes in fiscal years (FY) 2000 to 2004 (1 October 1999-30 September 2004). We calculated annual age- and sex-standardized rates of initial major, minor, and total amputations for the overall population and for various racial/ethnic groups (African Americans, Hispanics, and whites). Trends in ILEA risk were evaluated with and without adjustment for demographic characteristics and other potential risk factors, including presence of microvascular and macrovascular diseases, and antiglycemic treatment.Study populations of VHA patients with diabetes and without prior amputations ranged from 405,580 in FY 2000 to 739,377 in FY 2004. Age- and sex-standardized ILEA rates decreased by 34% (7.08/1,000 patients in FY 2000 to 4.65/1,000 patients in FY 2005) during the 5-year period. Minor and major amputation rates decreased by 33% (4.59 to 3.06/1,000) and 36% (2.49 to 1.59/1,000), respectively. Of major amputations, below-knee rates decreased from 1.08 to 0.87/1,000 (-19%), and above-knee decreased from 1.41 to 0.72/1,000 (-49%). Similar trends were seen for all racial groups. ILEA risk decreased by 28% (odds ratio 0.72 [95% CI 0.68-0.75]) when FY 2004 was compared with FY 2000 in the model, adjusting for demographic characteristics. This risk decrease was 22% in the model adjusting for all independent variables (odds ratio 0.78 [95% CI 0.74-0.82]).Downward 5-year trends in ILEA rates were observed for all amputation levels and among all racial groups, even after adjustment for risk differences over time.
Superior survival in primary systemic amyloidosis patients undergoing peripheral blood stem cell transplantation: a case-control study
Authors: Angela Dispenzieri, Robert A. Kyle, Martha Q. Lacy, Terry M. Therneau, Dirk R. Larson, Matthew F. Plevak, S. Vincent Rajkumar, Rafael Fonseca, Philip R. Greipp, Thomas E. Witzig, John A. Lust, Steven R. Zeldenrust, Denise S. Snow, Susan R. Hayman, Mark R. Litzow, Dennis A. Gastineau, Ayalew Tefferi, David J. Inwards, Ivana N. Micallef, Stephen M. Ansell, Luis F. Porrata, Michelle A. Elliott, Morie A. Gertz
Journal: Blood (2004)
Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force
Authors: Stephen P. Fortmann, Brittany U. Burda, Caitlyn A. Senger, Jennifer S. Lin, Evelyn P. Whitlock
Journal: Annals of Internal Medicine (2013)

Background: Vitamin and mineral supplements are commonly used to prevent chronic diseases. Purpose: To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. Data Sources: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. Study Selection: Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. Data Extraction: Dual quality assessments and data abstraction. Data Synthesis: Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers. Limitations: The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. Conclusion: Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. Primary Funding Source: Agency for Healthcare Research and Quality.
Cytomegalovirus encephalomyelomeningoradiculitis in acquired immunodeficiency syndrome (AIDS)
Authors: S. Lüttmann, I.W. Husstedt, N. Lügering, C. Heese, R. Stoll, W. Domschke, S. Evers, K. Kuchelmeister, F. Gullotta
Journal: Journal of Infection (1997)