tbuckley/cabot-search huggingface dataset:
Heparin decreases the rate of proliferation of rat vascular smooth muscle cells by releasing transforming growth factor -like activity from serum
Authors: D. J Grainger, C. M Witchell, J. V Watson, J. C Metcalfe, P. L Weissberg
Journal: Cardiovascular Research (1993)

Objectives: Various heparins have been reported to inhibit the proliferation of vascular smooth muscle cells (VSMCs). The effects of eight chemically distinct heparins on the cell cycle and differentiation of primary and passaged cultures of rat aortic VSMCs have been characterised and the mechanism of heparin action investigated. Methods: VSMCs from adult rat aorta were prepared by enzyme dispersion and stimulated to enter the cell cycle with 10% serum in the presence or absence of heparin. Progressions through S phase and M phase were measured by [3H]-thymidine incorporation and cell counting respectively. Flow cytometry was used to confirm the effects of heparin on VSMC cell cycle progression. The effect of heparin on VSMC differentiation was investigated by analysing smooth muscle specific myosin heavy chain content of the cells after heparin treatment. Results: Eight heparins at concentrations between 5 μg·ml−1 and 100 μg·ml−1 partially inhibited VSMC proliferation (27% to 16% 96 hours after addition of heparin), but did not affect the entry of the cells into S phase. Flow cytometry confirmed that VSMC populations in the presence of heparin contained significantly (p< 0.005) more cells in the G2/M phase of the cell cycle than control populations. Heparin also blocked the dedifferentiation of primary cultures of VSMCs stimulated by serum. These effects of heparin were completely reversed by the presence of a neutralising antiserum to transforming growth factor β (TGF β) and heparin attached to agarose beads was as effective as free heparin as a growth inhibitor of VSMCs. Conclusions: Heparins of varying molecular weight and anticoagulent properties all partially inhibited VSMC proliferation predominantly by extending the G2/M phase of the cell cycle. Heparin also inhibited dedifferentiation of primary cultures of VSMCs. Heparin (<100 μg·ml−1) acted extracellularly to release TGF β from serum, which accounted for the effects of heparin on proliferation and differentiation. Cardiovascular Research 1993;27:2238-2247
Infiltrating Duct Carcinoma of the Mammary Gland of a Rhesus Monkey After Administration of an Oral Contraceptive: A Preliminary Report
Authors: Ruth L. Kirschstein, Alan S. Rabson, George W. Rusten
Journal: JNCI Journal of the National Cancer Institute (1972)

6 mature female rhesus monkeys 6-8 years of age were given daily doses of the oral contraceptive Enovid 9.85 mg norethynodrel and .15 mg mestranol per tablet in 1 mg doses suspended in a small amount of ethanol and mixed with orange juice.  After 18 months 1 monkey died with an infiltrating duct carcinoma of the breast with metastases to axillary and internal mammary lymph nodes liver and lungs.  The remaining 5 monkeys are free of clinical evidence of disease after 2 years of Enovid administration.  Although the rarity of breast cancer in monkeys untreated with hormones suggests that Envoid may have played a role in the induction of this tumor the possibility of spontaneous origin cannot be excluded.(AUTHORS MODIFIED)
Granulin–Epithelin Precursor Overexpression Promotes Growth and Invasion of Hepatocellular Carcinoma
Authors: Siu Tim Cheung, San Yu Wong, Ka Ling Leung, Xin Chen, Samuel So, Irene O. Ng, Sheung Tat Fan
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Granulin–epithelin precursor (GEP) is a novel growth factor. Our earlier cDNA microarray study indicated that GEP was overexpressed in hepatocellular carcinoma (HCC). The aim of this study was to investigate the clinical significance of GEP expression and its potential as a therapeutic target in HCC. Experimental Design: A total of 110 pairs of HCCs and adjacent nontumor liver tissues, and 22 normal liver tissues were examined. The GEP RNA level was examined by quantitative reverse transcription-PCR, and protein localization by immunohistochemistry. The GEP function was examined by transfection experiments. Results: The RNA levels of the HCCs were significantly higher than those of the nontumor liver tissues and normal livers (P &amp;lt; 0.001). GEP protein staining was observed in tumor cytoplasm, and the GEP protein levels of the HCCs were also significantly higher than those of the nontumor liver tissues and normal livers (P &amp;lt; 0.001). The majority of HCCs demonstrated up-regulation of GEP protein compared with their adjacent liver tissues [79 (71.8%) of 110]. Positive correlation of GEP RNA with protein levels was observed in HCCs (P &amp;lt; 0.01). Strong GEP expression was associated with large HCCs, venous infiltration, and early intrahepatic recurrence (P &amp;lt; 0.05). Functional studies on the HCC cell line Hep3B demonstrated that reduction of GEP protein levels resulted in decreased cell prolifera-tion rates, tumor invasion ability, anchorage-independent growth in soft agar, and tumorigenicity in nude mice (P &amp;lt; 0.05). Conclusion: GEP is an important factor for HCC growth, invasion, and metastasis. GEP has the potential to serve as a tumor marker and therapeutic target.
Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis
Authors: Sofi G Julien, Nadia Dubé, Michelle Read, Janice Penney, Marilene Paquet, Yongxin Han, Brian P Kennedy, William J Muller, Michel L Tremblay
Journal: Nature Genetics (2007)
Thirty one years of herpes zoster in a rural practice.
Authors: J B Wilson
Journal: BMJ (1986)

The principal finding in this study of 151 cases of herpes zoster in a rural practice was the predominance of patients who had a lesion on the right side. This supports the proposition that the site of occurrence may be determined by repeated trauma. The decline in the frequency of attacks in older men was significant. Studying these cases and published reports has elucidated some of the problems of the occurrence and distribution of herpes zoster in the body, which still await definition. Others may be encouraged to carry these studies further.
ALDH2 Activator Inhibits Increased Myocardial Infarction Injury by Nitroglycerin Tolerance
Authors: Lihan Sun, Julio Cesar Batista Ferreira, Daria Mochly-Rosen
Journal: Science Translational Medicine (2011)

Nitroglycerin, which treats impaired cardiac function through vasodilation as it is converted to nitric oxide, is used worldwide for patients with various ischemic and congestive cardiac diseases, including angina pectoris. Nevertheless, after continuous treatment, the benefits of nitroglycerin are limited by the development of tolerance to the drug. Nitroglycerin tolerance is a result of inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme essential for cardioprotection in animals subjected to myocardial infarction. Here, we tested the hypothesis that the tolerance that develops as a result of sustained nitroglycerin treatment increases cardiac injury by subsequent myocardial infarction. In a rat model of myocardial infarction, 16 hours of prior, sustained nitroglycerin treatment resulted in infarcts that were twice as large as those in untreated control animals and in diminished cardiac function at 3 days and 2 weeks after the myocardial infarction. We also sought to identify a potential treatment to protect against this increased cardiac damage. Nitroglycerin inhibited ALDH2 activity in vitro, an effect that was blocked by Alda-1, an activator of ALDH2. Co-administration of Alda-1 with the nitroglycerin prevented the nitroglycerin-induced increase in cardiac dysfunction after myocardial infarction in rats, at least in part by enhancing metabolism of reactive aldehyde adducts that impair normal protein functions. If our animal studies showing that nitroglycerin tolerance increases cardiac injury upon ischemic insult are corroborated in humans, activators of ALDH2 such as Alda-1 may help to protect patients with myocardial infarction from this nitroglycerin-induced increase in cardiac injury while maintaining the cardiac benefits of the increased nitric oxide concentrations produced by nitroglycerin.
Does a Patient-Managed Insulin Intensification Strategy With Insulin Glargine and Insulin Glulisine Provide Similar Glycemic Control as a Physician-Managed Strategy? Results of the START (Self-Titration With Apidra to Reach Target) Study
Authors: Stewart B. Harris, Jean-François Yale, Lori Berard, John Stewart, Babak Abbaszadeh, Susan Webster-Bogaert, Hertzel C. Gerstein
Journal: Diabetes Care (2013)

OBJECTIVE Diabetes self-management is universally regarded as a foundation of diabetes care. We determined whether comparable glycemic control could be achieved by self-titration versus physician titration of a once-daily bolus insulin dose in patients with type 2 diabetes who are unable to achieve optimal glycemia control with a basal insulin. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes, an HbA1c level >7% (53 mmol/mol), and either nocturnal hypoglycemia episodes or an insufficient basal insulin glargine level (with or without oral agents) to achieve a fasting plasma glucose level ≤6 mmol/L (108 mg/dL) were studied. Participants all had bolus insulin glulisine added at breakfast and were allocated to either algorithm-guided patient self-titration or physician titration. The primary outcome was an HbA1c level ≤7% (53 mmol/mol) without severe hypoglycemia. RESULTS After a mean (SD) follow-up of 159.4 days (36.2 days), 28.4% of participants in the self-titration arm vs. 21.2% in the physician titration arm achieved an HbA1c level of ≤7% (53 mmol/mol) without severe hypoglycemia (between-group absolute difference 7.2%; 95% CI -3.2 to 17.7). The lower end of this 95% confidence interval was within the predetermined noninferiority boundary of -5% (P noninferiority = 0.011). CONCLUSIONS In stable patients with type 2 diabetes who are receiving doses of basal insulin glargine who require bolus insulin, a simple bolus insulin patient-managed titration algorithm is as effective as a physician-managed algorithm.
Social Values and Drug Use Among Psychiatric Patients
Authors: MELVIN COHEN, DONALD F. KLEIN
Journal: American Journal of Psychiatry (1972)

Two social values tests were given to young, middle-class drug abusers and to a control group of non-drug users to determine whether drug users rejected typical middle-class values significantly more often than non-drug users. The drug users rejected values that connoted the Protestant ethic more often than the non-drug users; however, they were not more rejecting of values, such as money, marriage, and job security, that would help them succeed in society.
Capecitabine (X) plus vinorelbine (N) as second-line therapy in Chinese patients (pts) with metastastic breast cancer (MBC)
Authors: B. Xu, L. Tian, Q. Wu, M. Zhou, H. Wang, Z. Tong, H. Li, L. Li, G. Hu, J. Shi
Journal: Journal of Clinical Oncology (2006)

10679 Background: Breast cancer is one of the most common malignancies among Chinese women and the incidence continues to rise, particularly in large cities such as Shanghai. X monotherapy is consistently effective and very well tolerated in pretreated MBC. N is also commonly used in this indication. In several studies, the combination of X + N led to response rates ranging from 43–67% in first-line MBC. As there are few data on this combination in pretreated MBC, we evaluated the efficacy and safety of X + N in Chinese pts with MBC refractory to anthracycline or taxane treatment in a phase II trial. Methods: 77 pts of a planned population of 60 pts were enrolled between Feb 2003 and Nov 2004. All pts had measurable MBC (WHO) recurrent after anthracycline or taxane treatment, Karnofsky PS ≥60, adequate bone marrow, renal and hepatic function. Pts received 3-weekly cycles of oral X 1000mg/m 2 bid d1–14 + i.v. N 25mg/m 2 d1&amp;8, for at least 2 cycles. Pts with progressive disease went off study while those with complete response (CR), partial response (PR), or stable disease (SD) continued treatment for a maximum of 6 cycles. Results: Baseline characteristics of the 77 pts evaluable to date: median age 51 years (range 29–68); median Karnofsky PS 90 (range 70–100). Previous chemotherapy was: anthracycline (87%), paclitaxel/docetaxel (52%). Principal tumor sites were: lung (40%), liver (39%), lymph nodes (33%), thoracic wall (12%), breast (7%), other (3%). All pts received at least 2 cycles, 20 received 4 cycles and 47 received 6 cycles. The overall response rate was 22%, including 5 CR and 12 PR. At a median follow-up of 6 months (95% CI, 4.2–9.0), the median time to progression (TTP) is 6 months (95% CI, 3.5–9.0). The most common (≥10% pts) treatment-related grade 1/2 adverse events were: HFS (16%), nausea (12%), and SGPT abnormality (10%). Most adverse events improved or resolved after dose adjustment and/or suitable treatments. There were very few grade 3/4 adverse events, the most common being leucopenia (12%). Conclusions: X + N is active in pretreated MBC and its efficacy is confirmed in this study in Chinese pts. The combination is also well tolerated. No significant financial relationships to disclose.
CXCR4/fusin Is Not a Species-specific Barrier in Murine Cells for HIV-1 Entry
Authors: Kazunobu Tachibana, Toshihiro Nakajima, Akihiko Sato, Kenji Igarashi, Hisatoshi Shida, Hisashi Iizasa, Nobuaki Yoshida, Osamu Yoshie, Tadamitsu Kishimoto, Takashi Nagasawa
Journal: The Journal of Experimental Medicine (1997)

Since some murine cells expressing human CD4 fail to internalize HIV-1, another block was thought to be located at the level of viral entry in addition to CD4. Recently, CXCR4 was shown to function as a coreceptor for T cell line-tropic HIV-1 entry. Here we demonstrated that cells expressing murine CXCR4 and human CD4 fused with cells expressing the env proteins derived from T cell line-tropic HIV-1 and were infected with T cell line-tropic HIV-1 strains. In contrast, the same cells were not infected with chimeric clones constructed by substitution of monocyte- or macrophage-tropic strain-derived env region or V3 region into T cell line-tropic HIV-1, indicating V3 loop of envelope protein is required for murine CXCR4mediated HIV-1 entry. We conclude that murine CXCR4 is not a species specific barrier to the entry of T cell line-tropic HIV-1.
Defining NOTCH3 Target Genes in Ovarian Cancer
Authors: Xu Chen, Michelle M. Thiaville, Li Chen, Alexander Stoeck, Jianhua Xuan, Min Gao, Ie-Ming Shih, Tian-Li Wang
Journal: Cancer Research (2012)

Abstract NOTCH3 gene amplification plays an important role in the progression of many ovarian and breast cancers, but the targets of NOTCH3 signaling are unclear. Here, we report the use of an integrated systems biology approach to identify direct target genes for NOTCH3. Transcriptome analysis showed that suppression of NOTCH signaling in ovarian and breast cancer cells led to downregulation of genes in pathways involved in cell-cycle regulation and nucleotide metabolism. Chromatin immunoprecipitation (ChIP)-on-chip analysis defined promoter target sequences, including a new CSL binding motif (N1) in addition to the canonical CSL binding motif, that were occupied by the NOTCH3/CSL transcription complex. Integration of transcriptome and ChIP-on-chip data showed that the ChIP target genes overlapped significantly with the NOTCH-regulated transcriptome in ovarian cancer cells. From the set of genes identified, we showed that the mitotic apparatus organizing protein DLGAP5 (HURP/DLG7) was a critical target. Both the N1 motif and the canonical CSL binding motif were essential to activate DLGAP5 transcription. DLGAP5 silencing in cancer cells suppressed tumorigenicity and inhibited cellular proliferation by arresting the cell cycle at the G2–M phase. In contrast, enforced expression of DLGAP5 partially counteracted the growth inhibitory effects of a pharmacologic or RNA interference–mediated NOTCH inhibition in cancer cells. Our findings define direct target genes of NOTCH3 and highlight the role of DLGAP5 in mediating the function of NOTCH3. Cancer Res; 72(9); 2294–303. ©2012 AACR.
Evaluation of myocardial function in patients with rheumatoid arthritis using strain imaging by speckle-tracking echocardiography
Authors: Nowell M Fine, Cynthia S Crowson, Grace Lin, Jae K Oh, Hector R Villarraga, Sherine E Gabriel
Journal: Annals of the Rheumatic Diseases (2013)

Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD), although strategies to detect subclinical CVD are poorly characterised. The purpose of this study was to assess myocardial function by speckle-tracking echocardiography strain imaging in patients with RA without known CVD.
Multifunctional regulation of angiogenesis by high-density lipoproteins
Authors: Hamish C.G. Prosser, Joanne T.M. Tan, Louise L. Dunn, Sanjay Patel, Laura Z. Vanags, Shisan Bao, Martin K.C. Ng, Christina A. Bursill
Journal: Cardiovascular Research (2013)

High-density lipoproteins (HDL) exert striking anti-inflammatory effects and emerging evidence suggests that they may augment ischaemia-mediated neovascularization. We sought to determine whether HDL conditionally regulates angiogenesis, depending on the pathophysiological context by (i) inhibiting inflammation-induced angiogenesis, but also; (ii) enhancing ischaemia-mediated angiogenesis. Intravenously delivered apolipoprotein (apo) A-I attenuated neovascularization in the murine femoral collar model of inflammation-induced angiogenesis, compared with phosphate-buffered saline infused C57BL6/J mice (58%), P < 0.05. Conversely, apoA-I delivery augmented neovessel formation (75%) and enhanced blood perfusion (45%) in the murine hindlimb ischaemia model, P < 0.05. Reconstituted HDL (rHDL) was tested on key angiogenic cell functions in vitro. rHDL inhibited human coronary artery endothelial cell migration (37.9 and 76.9%), proliferation (15.7 and 40.4%), and tubulogenesis on matrigel (52 and 98.7%) when exposed to two inflammatory stimuli: tumour necrosis factor-α (TNF-α) and macrophage-conditioned media (MCM). In contrast, rHDL significantly augmented hypoxia-stimulated migration (36.9%), proliferation (135%), and tubulogenesis (22.9%), P < 0.05. Western blot and RT–PCR analyses revealed that these divergent actions of rHDL were associated with conditional regulation of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and VEGF receptor 2, which were attenuated in response to TNF-α (40.4, 41.0, and 33.2%) and MCM (72.5, 30.7, and 69.5%), but augmented by rHDL in hypoxia (39.8, 152.6, and 15.7%%), all P < 0.05. HDL differentially regulates angiogenesis dependent upon the pathophysiological setting, characterized by suppression of inflammation-associated angiogenesis, and conversely, by the enhancement of hypoxia-mediated angiogenesis. This has significant implications for therapeutic modulation of neovascularization.
Telomerase expression in idiopathic pulmonary fibrosis (IPF) and non small cell lung cancer (NSCLC)
Authors: Katerina Samara, Ismini Lasithiotaki, Giannoula Soufla, Ioannis Giannarakis, Maria Velivassaki, Anna Psaraki, Nikolaos Siafakas, Katerina Antoniou
Journal: European Respiratory Journal (2012)

Rationale: Telomeres protect chromosome ends since chromosomes lacking telomeres undergo fusion, rearrangement and translocation. Telomerase dysfunction has been linked with pathologic autoimmune responses and could play a role in both fibrogenesis and carcinogenesis. We aim to evaluate telomerase expression (mRNA levels of both subunits TERT and TERC) in Bronchoalveolar Lavage Fluid (BALF) and lung tissue of patients with NSCLC and IPF, since there are indications of common pathogenetic pathways in both diseases.

Patients and Methods: We prospectively studied 44 BALF samples from NSCLC patients, 29 BALF samples from IPF patients and 13 BALF samples from control subjects. We also studied lung tissue samples from 32 IPF patients, 10 NSCLC patients and 21 control subjects. mRNA expression for both hTERT and hTERC was measured by Real-Time RT-PCR.

Results: (a) Lung tissue: IPF mRNA hTERT levels (0.24±0.14) were significantly lower compared to controls (0.46±0.30) (p=0.030). hTERC mRNA levels were higher in the control group (4.3±1.9) compared to NSCLC (2.87±1.51) and IPF (1.21±0.97), with strong grouped statistical significance (p=0.0001). (b) BALF: hTERT expression was higher in the control group (0.78±0.06) compared to IPF (0.39±0.14) and NSCLC (0.34±0.29) (p=0.005). hTERC expression was higher in the IPF group (1.09±0.39) compared to controls (0.54±0.40) and NSCLC (0.62±0.19), with no grouped statistical significance.

Conclusion: The attenuated expression of both telomerase subunits measured in NSCLC and IPF patients when compared to controls, suggests that telomerase genes may play a significant role in fibrogenesis and carcinogenesis, supporting the hypothesis of a common pathway.
Regulation of Bone Morphogenetic Protein-2 Expression in Endothelial Cells
Authors: Anna Csiszar, Kira E. Smith, Akos Koller, Gabor Kaley, John G. Edwards, Zoltan Ungvari
Journal: Circulation (2005)

Recent studies suggest that bone morphogenetic protein-2 (BMP-2), a transforming growth factor-beta superfamily member cytokine, plays an important role both in vascular development and pathophysiological processes, including endothelial activation that is likely to contribute to the development of coronary atherosclerosis, yet the factors that regulate arterial expression of BMP-2 are completely unknown. We tested the hypothesis that BMP-2 expression in endothelial cells is governed by an H2O2 and nuclear factor (NF)-kappaBeta-dependent pathway that can be activated by both proinflammatory and mechanical stimuli.The proinflammatory cytokine tumor necrosis factor (TNF)-alpha induced NF-kappaBeta activation and elicited significant increases in BMP-2 mRNA and protein in primary coronary arterial endothelial cells and human umbilical vein endothelial cells that were prevented by NF-kappaBeta inhibitors (pyrrolidine dithiocarbamate and SN-50), silencing of p65 (siRNA), or catalase. Administration of H2O2 also elicited NF-kappaBeta activation and BMP-2 induction. In organ culture, exposure of rat arteries to high pressure (160 mm Hg) elicited H2O2 production, nuclear translocation of NF-kappaBeta, and upregulation of BMP-2 expression. Although high pressure upregulated TNF-alpha, it appears that it directly regulates BMP-2 expression, because upregulation of BMP-2 was also observed in vessels of TNF-alpha knockout mice.Vascular BMP-2 expression can be regulated by H2O2-mediated activation of NF-kappaBeta both by inflammatory stimuli and by high intravascular pressure.