tbuckley/cabot-search huggingface dataset:
Parathyroid Hormone Regulates Fibroblast Growth Factor-23 in a Mouse Model of Primary Hyperparathyroidism
Authors: Takehisa Kawata, Yasuo Imanishi, Keisuke Kobayashi, Takami Miki, Andrew Arnold, Masaaki Inaba, Yoshiki Nishizawa
Journal: Journal of the American Society of Nephrology (2007)

The importance of fibroblast growth factor 23 (FGF-23) in the pathogenesis of phosphate wasting disorders has been established, but controversy remains about how parathyroid hormone (PTH), which also stimulates urinary phosphate excretion, regulates the circulating level of FGF-23. We found that the serum FGF-23 concentration was higher in PTH-cyclin D1 transgenic mice, a model of primary hyperparathyroidism, than in wild-type mice. The serum FGF-23 concentration was significantly and directly correlated with serum PTH and calcium, and inversely correlated with phosphate levels in 90- to 118-week-old mice (all P < 0.005). Quantitative real-time reverse-transcriptase PCR revealed abundant expression of fgf23 in bone, especially in calvaria. The fgf23 expression in calvaria was significantly higher in the transgenic mice compared to the wild-type mice, and correlated well with serum FGF-23 levels. There was a direct correlation between the expression of fgf23 and the expression of osteocalcin and ALP, suggesting that activation of osteoblasts is important in the regulation of FGF-23. Serum FGF-23 levels decreased in the transgenic mice after parathyroidectomy. In conclusion, PTH plays a major role in the regulation of serum FGF-23 level in primary hyperparathyroidism, likely via activation of osteoblasts in bone.
Inflammation in the Prediabetic State Is Related to Increased Insulin Resistance Rather Than Decreased Insulin Secretion
Authors: Andreas Festa, Anthony J.G. Hanley, Russell P. Tracy, Ralph D’Agostino, Steven M. Haffner
Journal: Circulation (2003)

Elevated levels of proinflammatory proteins are predictive of both cardiovascular (CV) disease and type 2 diabetes. Previously, atherogenic changes in traditional CV risk factors in the prediabetic state were mainly seen in insulin-resistant subjects rather than in those with a predominant defect in insulin secretion.We studied in prediabetic individuals from the Insulin Resistance Atherosclerosis Study (IRAS) the relation of C-reactive protein (CRP), plasminogen activator inhibitor (PAI)-1, and fibrinogen to defects in insulin sensitivity (SI) and first-phase insulin secretion, respectively, as assessed using a frequently sampled intravenous glucose tolerance test. One hundred forty-eight of 906 (16.3%) nondiabetic individuals developed diabetes after a mean follow-up of 5.2 years. Prediabetic individuals who were insulin resistant had higher levels of PAI-1 (mean [95% CI], 25.83 ng/mL [22.42 to 29.77] versus 16.31 ng/mL [12.56 to 21.18]; P=0.003) and CRP (mean [95% CI], 2.88 mg/L [2.33 to 3.56] versus 1.68 mg/L [1.13 to 2.49]; P=0.018) than insulin-sensitive individuals, but individuals with decreased acute insulin response tended to have lower rather than higher levels of inflammatory proteins compared with those with high insulin secretion. Prediabetic subjects who were predominantly insulin resistant had higher levels of inflammatory proteins compared with both prediabetic subjects with decreased insulin secretion as well as nonconverters. By contrast, prediabetic subjects with a predominant defect in first-phase insulin secretion had levels of inflammatory proteins indistinguishable from those in nonconverters.We have shown an increased proinflammatory state in prediabetic individuals who are predominantly insulin resistant but not in those with a primary defect in beta-cell function. These results provide additional evidence that prediabetic subjects may be at an increased risk of heart disease, and this risk seems to be restricted to subjects with high insulin resistance.
Definition of Smad3 Phosphorylation Events That Affect Malignant and Metastatic Behaviors in Breast Cancer Cells
Authors: Eunjin Bae, Misako Sato, Ran-Ju Kim, Mi-Kyung Kwak, Kazuhito Naka, Jungsoo Gim, Mitsutaka Kadota, Binwu Tang, Kathleen C. Flanders, Tae-Aug Kim, Sun-Hee Leem, Taesung Park, Fang Liu, Lalage M. Wakefield, Seong-Jin Kim, Akira Ooshima
Journal: Cancer Research (2014)

Smad3, a major intracellular mediator of TGFβ signaling, functions as both a positive and negative regulator in carcinogenesis. In response to TGFβ, the TGFβ receptor phosphorylates serine residues at the Smad3 C-tail. Cancer cells often contain high levels of the MAPK and CDK activities, which can lead to the Smad3 linker region becoming highly phosphorylated. Here, we report, for the first time, that mutation of the Smad3 linker phosphorylation sites markedly inhibited primary tumor growth, but significantly increased lung metastasis of breast cancer cell lines. In contrast, mutation of the Smad3 C-tail phosphorylation sites had the opposite effect. We show that mutation of the Smad3 linker phosphorylation sites greatly intensifies all TGFβ-induced responses, including growth arrest, apoptosis, reduction in the size of putative cancer stem cell population, epithelial-mesenchymal transition, and invasive activity. Moreover, all TGFβ responses were completely lost on mutation of the Smad3 C-tail phosphorylation sites. Our results demonstrate a critical role of the counterbalance between the Smad3 C-tail and linker phosphorylation in tumorigenesis and metastasis. Our findings have important implications for therapeutic intervention of breast cancer.
Systemic haemodynamics in borderline arterial hypertension: responses to static exercise before and under the influence of propranolol
Authors: R. SANNERSTEDT, S. JULIUS
Journal: Cardiovascular Research (1972)

Journal Article Systemic haemodynamics in borderline arterial hypertension: responses to static exercise before and under the influence of propranolol Get access RUNE SANNERSTEDT, RUNE SANNERSTEDT 2 From the Department of Internal Medicine (Hypertension Unit), University of Michigan Medical School, Ann Arbor, Michigan 48104, U.S.A. 2 Present address: AB Hässle, S-402 20, Göteborg 5, Sweden. Search for other works by this author on: Oxford Academic PubMed Google Scholar STEVO JULIUS STEVO JULIUS From the Department of Internal Medicine (Hypertension Unit), University of Michigan Medical School, Ann Arbor, Michigan 48104, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 6, Issue 4, July 1972, Pages 398–403, https://doi.org/10.1093/cvr/6.4.398 Published: 01 July 1972
Strong modularity and circular reasoning pervade the planning–control model
Authors: Verónica C. Ramenzoni, Michael A. Riley
Journal: Behavioral and Brain Sciences (2004)

We believe the dichotomy of processes introduced in the target article is highly speculative, because the dichotomy is shaped by the questionable assumption of modularity and the complementary assumption of locality. As a result, the author falls into a line of circular reasoning that biases his analysis of the experimental and neuropsychological data, and weakens the proposed model.
Identification of circulating tumour cells in early stage breast cancer patients using multi marker immunobead RT-PCR
Authors: Michael P Raynor, Sally-Anne Stephenson, Kenneth B Pittman, David CA Walsh, Michael A Henderson, Alexander Dobrovic
Journal: Journal of Hematology & Oncology (2009)

Abstract Introduction The ability to screen blood of early stage operable breast cancer patients for circulating tumour cells is of potential importance for identifying patients at risk of developing distant relapse. We present the results of a study of the efficacy of the immunobead RT-PCR method in identifying patients with circulating tumour cells. Results Immunomagnetic enrichment of circulating tumour cells followed by RT-PCR (immunobead RT-PCR) with a panel of five epithelial specific markers ( ELF3 , EPHB4 , EGFR , MGB1 and TACSTD1 ) was used to screen for circulating tumour cells in the peripheral blood of 56 breast cancer patients. Twenty patients were positive for two or more RT-PCR markers, including seven patients who were node negative by conventional techniques. Significant increases in the frequency of marker positivity was seen in lymph node positive patients, in patients with high grade tumours and in patients with lymphovascular invasion. A strong trend towards improved disease free survival was seen for marker negative patients although it did not reach significance (p = 0.08). Conclusion Multi-marker immunobead RT-PCR analysis of peripheral blood is a robust assay that is capable of detecting circulating tumour cells in early stage breast cancer patients.
Deficiency of Th17 cells in hyper IgE syndrome due to mutations in <i>STAT3 </i>
Authors: Cindy S. Ma, Gary Y.J. Chew, Nicholas Simpson, Archana Priyadarshi, Melanie Wong, Bodo Grimbacher, David A. Fulcher, Stuart G. Tangye, Matthew C. Cook
Journal: The Journal of Experimental Medicine (2008)

Hyper-immunoglobulin E syndrome (HIES) is a primary immune deficiency characterized by abnormal and devastating susceptibility to a narrow spectrum of infections, most commonly Staphylococcus aureus and Candida albicans. Recent investigations have identified mutations in STAT3 in the majority of HIES patients studied. Despite the identification of the genetic cause of HIES, the mechanisms underlying the pathological features of this disease remain to be elucidated. Here, we demonstrate a failure of CD4+ T cells harboring heterozygous STAT3 mutations to generate interleukin 17-secreting (i.e., T helper [Th]17) cells in vivo and in vitro due to a failure to express sufficient levels of the Th17-specific transcriptional regulator retinoid-related orphan receptor t. Because Th17 cells are enriched for cells with specificities against fungal antigens, our results may explain the pattern of infection susceptibility characteristic of patients with HIES. Furthermore, they underscore the importance of Th17 responses in normal host defense against the common pathogens S. aureus and C. albicans.
The transfer factor and its subdivisions in patients with pulmonary emboli
Authors: AG Fennerty, KA Gunawardena, AP Smith
Journal: European Respiratory Journal (1988)

The carbon monoxide transfer factor and its subdivisions, the pulmonary membrane diffusing capacity and the pulmonary capillary volume were measured in fourteen subjects following submassive pulmonary emboli, as demonstrated by a ventilation-perfusion scan, and in fourteen matched controls. Transfer factor and alveolar volume were significantly lower in patients with pulmonary emboli (p less than 0.02). Patients were given six weeks anticoagulant therapy and the measurements repeated three months later. There was a significant increase in the transfer factor and the alveolar volume (p less than 0.01) and the membrane diffusing capacity (p less than 0.05). It has previously been assumed that the reduction in the transfer factor following a pulmonary embolus is due to a reduction in the pulmonary capillary volume. Results of this study however, suggest that it is more likely to be due to a loss of alveolar volume, at least in subjects with submassive emboli.
Angiotensin II Type 1–Receptor Mediated Changes in Heparan Sulfate Proteoglycans in Human SV40 Transformed Podocytes
Authors: Paul-Thomas Brinkkoetter, Simone Holtgrefe, Fokko J. van der Woude, Benito A. Yard
Journal: Journal of the American Society of Nephrology (2004)

In patients with diabetic nephropathy, glomerular staining for heparan sulfate proteoglycans (HSPG) side chains and for agrin is decreased. In the present study, the influence of angiotensin II (AngII) on the production of HSPG in SV40 transformed podocytes was investigated. SV40 transformed human podocytes were cultivated with or without 1 microM AngII, and HSPG production was measured by sequential DEAE-anion exchange chromatography and HPLC-DEAE separation. Expression of agrin was studied by indirect immunofluorescence and Western blot analysis using specific mono- and polyclonal antibodies. DEAE separation of total glycosaminoglycans (GAG) revealed a significant increase of GAG in the culture supernatant and decrease in the cell and matrix layer when podocytes were cultured for 72 h in the presence of AngII. This was particularly found for HS-GAG. Qualitative analysis of HSPG, using gel filtration of HNO(2)-treated fractions, showed that AngII treatment decreased N-sulfation of HS-GAG side chains. Indirect immunofluorescence staining with anti-agrin polyclonal antibody was strongly decreased after AngII stimulation. A reduction in agrin expression in cell extracts could also be detected in Western blot analysis using an mAb. No changes in agrin mRNA were found after AngII stimulation. It is concluded from this study that AngII decreases the amount of HSPG on the cell surface and in the extracellular matrix of podocytes. Because HSPG play a fundamental role in the permselectivity of the glomerular basement membrane, these results thus may explain at least partially the antiproteinuric effects of angiotensin-converting enzyme inhibition in patients with diabetic nephropathy.
Divided naevus on the penis
Authors: G‐S. Choi, D‐H. Won, S‐J. Lee, J‐H. Lee, Y‐G. Kim
Journal: British Journal of Dermatology (2000)

Journal Article Divided naevus on the penis Get access G‐S. Choi, G‐S. Choi Department of Dermatology, College of Medicine, Inha University Hospital, 7–206 3rd Street, Shinheung‐Dong, Choong‐Gu, Inchon 400–103, Korea Search for other works by this author on: Oxford Academic Google Scholar D‐H. Won, D‐H. Won Department of Dermatology, College of Medicine, Inha University Hospital, 7–206 3rd Street, Shinheung‐Dong, Choong‐Gu, Inchon 400–103, Korea Search for other works by this author on: Oxford Academic Google Scholar S‐J. Lee, S‐J. Lee Department of Dermatology, College of Medicine, Inha University Hospital, 7–206 3rd Street, Shinheung‐Dong, Choong‐Gu, Inchon 400–103, Korea Search for other works by this author on: Oxford Academic Google Scholar J‐H. Lee, J‐H. Lee Department of Dermatology, College of Medicine, Inha University Hospital, 7–206 3rd Street, Shinheung‐Dong, Choong‐Gu, Inchon 400–103, Korea Search for other works by this author on: Oxford Academic Google Scholar Y‐G. Kim Y‐G. Kim Department of Dermatology, College of Medicine, Inha University Hospital, 7–206 3rd Street, Shinheung‐Dong, Choong‐Gu, Inchon 400–103, Korea Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 5, 1 November 2000, Pages 1126–1127, https://doi.org/10.1046/j.1365-2133.2000.03814.x Published: 01 November 2000
UK's first private medical school will open in September 2008
Authors: Rebecca Coombes
Journal: BMJ (2007)

Britain's first private medical school will take students from next September, amid doubts that all of its graduates will be able to get jobs in the NHS.

The school, which will be based at the University of Buckingham, an independent university, will open with a modest intake of 25 postgraduate students. It will train already qualified doctors and will award a clinical MD.

The school's board, whose members include Luke Johnson, the former chairman of the Pizza Express chain of restaurants and current chairman of Channel 4 television, is involved in raising £12m (€17m; $25m) to launch a second …
Aristolactam-DNA adducts are a biomarker of environmental exposure to aristolochic acid
Authors: Bojan Jelaković, Sandra Karanović, Ivana Vuković-Lela, Frederick Miller, Karen L. Edwards, Jovan Nikolić, Karla Tomić, Neda Slade, Branko Brdar, Robert J. Turesky, Želimir Stipančić, Damir Dittrich, Arthur P. Grollman, Kathleen G. Dickman
Journal: Kidney International (2011)
Iron Sucrose Accelerates Early Atherogenesis by Increasing Superoxide Production and Upregulating Adhesion Molecules in CKD
Authors: Ko-Lin Kuo, Szu-Chun Hung, Tzong-Shyuan Lee, Der-Cherng Tarng
Journal: Journal of the American Society of Nephrology (2014)

High-dose intravenous iron supplementation is associated with adverse cardiovascular outcomes in patients with CKD, but the underlying mechanism is unknown. Our study investigated the causative role of iron sucrose in leukocyte-endothelium interactions, an index of early atherogenesis, and subsequent atherosclerosis in the mouse remnant kidney model. We found that expression levels of intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and adhesion of U937 cells increased in iron-treated human aortic endothelial cells through upregulated NADPH oxidase (NOx) and NF-κB signaling. We then measured mononuclear-endothelial adhesion and atherosclerotic lesions of the proximal aorta in male C57BL/6 mice with subtotal nephrectomy, male apolipoprotein E-deficient (ApoE(-/-)) mice with uninephrectomy, and sham-operated mice subjected to saline or parenteral iron loading. Iron sucrose significantly increased tissue superoxide production, expression of tissue cell adhesion molecules, and endothelial adhesiveness in mice with subtotal nephrectomy. Moreover, iron sucrose exacerbated atherosclerosis in the aorta of ApoE(-/-) mice with uninephrectomy. In patients with CKD, intravenous iron sucrose increased circulating mononuclear superoxide production, expression of soluble adhesion molecules, and mononuclear-endothelial adhesion compared with healthy subjects or untreated patients. In summary, iron sucrose aggravated endothelial dysfunction through NOx/NF-κB/CAM signaling, increased mononuclear-endothelial adhesion, and exacerbated atherosclerosis in mice with remnant kidneys. These results suggest a novel causative role for therapeutic iron in cardiovascular complications in patients with CKD.
Infliximab inhibits bone resorption by circulating osteoclast precursor cells in patients with rheumatoid arthritis and ankylosing spondylitis
Authors: M Gengenbacher, H-J Sebald, P M Villiger, W Hofstetter, M Seitz
Journal: Annals of the Rheumatic Diseases (2007)

To examine the effects of infliximab on bone resorption by osteoclast precursor cells (OCPs) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to compare the results with changes in disease activity.Before and during 24 weeks of infliximab treatment, peripheral blood mononuclear cells of 9 RA and 10 AS patients were seeded onto ivory wafers and adherent cells, including OCPs, were grown in medium promoting osteoclast differentiation. Bone resorption was evaluated morphometrically and correlated to disease activity. A total of 19 healthy individuals were studied in parallel. In addition, biochemical bone markers were assessed in all patients at baseline and after 24 weeks.OCPs from RA patients showed a higher bone resorption at baseline when compared to AS patients. Blocking of tumour necrosis factor (TNF)alpha with infliximab resulted in a strong reduction of bone resorption by OCPs in both cohorts and occurred faster in RA compared to AS patients. This inhibition coincided with a reduction of clinical disease activity in both patient cohorts and with an increase of serum osteocalcin levels and a relative decrease of collagen crosslinks in RA compared to AS patients.These results provide an explanation on the cellular level for the anticatabolic effect of TNF neutralisation on bone. The variation in the kinetics of bone resorption by the OCPs in patients with RA and AS suggests disease-specific differences in the type or in the preactivation of OCPs.
Hyperemic response of the coronary circulation to brief diastolic occlusion in the conscious dog.
Authors: G G Schwartz, P A McHale, J C Greenfield
Journal: Circulation Research (1982)

This study was undertaken to determine whether coronary blood flow can be regulated in response to coronary arterial occlusions briefer than a single diastole. The possible involvement of metabolic vs. myogenic mechanisms in such regulation was investigated. Eleven conscious dogs with experimentally produced complete heart block, chronically implanted electromagnetic flow probes, and pneumatic occluders on the left circumflex coronary artery were studied. Diastolic coronary occlusions lasting 100 to 400 msec were performed at paced heart rates of 40, 60, and 120 beats/min. At a heart rate of 60 beats/min, a 200-msec occlusion was sufficiently long to produce a significant reactive hyperemic response; 400-mec occlusions resulted in larger responses, while 100-msec occlusions did not generate a discernible response. The onset of reactive hyperemia was delayed from the end of the occlusion until the first post-occlusion systole. The length of this delay could be altered by changing the heart rate or occlusion duration, but no significant response was detected before the first post-occlusion systole. This characteristic of the data is more consistent with a metabolic than with a myogenic mechanism. If the response is metabolic, the data demonstrate that autoregulation of coronary flow by such a mechanism is very rapid, occurring during the first systole in which a flow deficit is detected by the myocardium.
Safety of Contrast Agent Use During Stress Echocardiography
Authors: Sahar S. Abdelmoneim, Mathieu Bernier, Christopher G. Scott, Abhijeet Dhoble, Sue Ann C. Ness, Mary E. Hagen, Stuart Moir, Robert B. McCully, Patricia A. Pellikka, Sharon L. Mulvagh
Journal: JACC. Cardiovascular imaging (2009)
Bexarotene Is Effective and Safe for Treatment of Refractory Advanced-Stage Cutaneous T-Cell Lymphoma: Multinational Phase II-III Trial Results
Authors: Madeleine Duvic, Kenneth Hymes, Peter Heald, Debra Breneman, Ann G. Martin, Patricia Myskowski, Connie Crowley, Richard C. Yocum
Journal: Journal of Clinical Oncology (2001)

Cutaneous T-cell lymphomas (CTCL) are malignancies of T cells appearing as skin lesions and are responsive to retinoid therapy. Safety and efficacy of a novel RXR-selective retinoid (rexinoid) bexarotene (Targretin, LGD1069; Ligand Pharmaceuticals Inc, San Diego, CA) was evaluated as a single-agent oral therapy administered once daily in an open-label study in patients with refractory advanced-stage CTCL.Ninety-four patients with biopsy-confirmed CTCL in advanced stages (IIB-IVB) were enrolled at 26 centers. Fifty-six patients received an initial dose of 300 mg/m2/d oral bexarotene and 38 started at more than 300 mg/m2/d.Clinical complete and partial responses were reported by Primary End point Classification for the study in 45% (25 of 56) of patients enrolled at 300 mg/m2/d dosing. At more than 300 mg/m2/d, 55% (21 of 38) of patients responded, including 13% (five of 38) clinical complete. For the 300 mg/m2/d initial dose group, the rate of relapse after response was 36% and the projected median duration of response was 299 days. Improvements were also seen in overall body-surface area involvement, median index lesion surface area, adenopathy, cutaneous tumors, pruritus, and CTCL-specific quality of life. The most frequent drug-related adverse events included hypertriglyceridemia (associated rarely with pancreatitis), hypercholesterolemia, hypothyroidism, and headache.Bexarotene is the first in a novel class of pharmacologic agents, the RXR-selective retinoids, or rexinoids. Bexarotene is orally administered, safe, and generally well tolerated with reversible side effects, and is effective for the treatment of advanced, refractory CTCL.