tbuckley/cabot-search huggingface dataset:
Treatment of Prolactin-Secreting Pituitary Macroadenomas with the Long-acting Non-Ergot Dopamine Agonist CV 205-502
Authors: Mary Lee Vance, Maurice Lipper, Anne Klibanski, Beverly M. K. Biller, Naguib A. Samaan, Mark E. Molitch
Journal: Annals of Internal Medicine (1990)

Study Objective: Evaluation of the effects of an experimental long-acting non-ergot dopamine agonist, CV 205-502, on serum prolactin, tumor size, gonadal function, visual abnormalities, and tolerability in patients with macroprolactinomas. Design: Prospective, unblinded, dose escalation as needed. Setting: Four university medical centers; patients referred for treatment. Patients: Twenty-six hyperprolactinemic patients (prolactin > 150 µg/L) with a pituitary macroadenoma were treated for 24 weeks with CV 205-502 given once daily. Measurements and Main Results: Serum prolactin was measured at regular intervals. Prolactin levels decreased in all patients during treatment (mean pretreatment level, 2051.7 ±1077 µg/L [± SE]; 24 weeks, 39.0 ±11.3 µg/L; P = 0.0001); normal prolactin levels were achieved in 15 (58%). Tumor size decreased in 21 of 26 patients and ranged from 6% to 67% (mean, 19.2% ± 3.4%). Onset or return of regular menses occurred in 11 of 15 premenopausal women, accompanied by an increase in estradiol concentrations (pretreatment, 186.5 ± 25.0 pmol/L; on treatment, 690.9 ± 104.3 pmol/L; P = 0.0003). Serum testosterone increased in 6 of 8 men; sexual function improved in 5 of 7 with pretreatment abnormalities. Two patients with reversible visual abnormalities improved within 2 weeks of starting treatment. Side effects occurred in 11 patients and abated over 1 to 2 weeks or after the dose was reduced. There was no evidence of toxicity as indicated by serial serum chemistries, liver function tests, hematologic profiles, thyroxine levels, and electrocardiogram studies. Conclusions: CV 205-502 reverses hyperprolactinemia and promotes reduction in tumor size with reversal of visual abnormalities and restoration of gonadal function in most patients. This compound will probably be useful in treating prolactinomas.
Response to Comment on Cefalu et al. The Alarming and Rising Costs of Diabetes and Prediabetes: A Call for Action! Diabetes Care 2014;37:3137–3138
Authors: William T. Cefalu, Matthew P. Petersen, Robert E. Ratner
Journal: Diabetes Care (2015)

We thank Yudkin and Montori (1) for their letter in response to our editorial (2).

As outlined in the editorial, we feel a great deal of attention—perhaps too much—has been paid over the recent past to the fact that the ranges of impaired glucose tolerance, impaired fasting glucose, and A1C define different groups of people as being at risk, and that the individuals with dysglycemic levels at the lower ends of the glycemic ranges are at lower risk for progressing to diabetes than the individuals at the higher ends. We would agree that all of that has been well established. In fact, American Diabetes Association (ADA) guidelines expressly acknowledge these points, but we do not see the value in repeatedly and exhaustively making these observations. We can continue to argue over what the exact diagnostic cut points for each test should be, but …
Hospital culture shock
Authors: E. G Bos
Journal: BMJ (1996)

Anybody who goes to work in a different part of the world should expect a culture shock. Faced with unfamiliar attitudes and customs you are constantly uncertain about how to behave and, therefore, ill at ease. Before we left for the Middle East we read a lot about Arab culture and customs and tried to fit in some language study as well. We now feel most stress not in the shops or with the language but where we did not expect it, in our medical work in the culture of the hospital.

We work in the Arabian Gulf alongside mostly Indian doctors. Our hospital began life a century ago as a charitable institution. When the increasing standard of living made it possible to charge a fee our hospital started doing so. We now function as a small, private, open access hospital with a total workforce of about 220 people. The general health of the people is excellent and most speak English well enough for …
Assessment of the functional status of heart failure in non ischemic dilated cardiomyopathy: an echo-dobutamine study
Authors: I Paraskevaidis
Journal: Cardiovascular Research (1999)

The functional status of heart failure (HF) is conventionally evaluated by peak exercise oxygen consumption (VO2 max). Dobutamine echocardiography can be used to evaluate myocardial reserve. The aim of this study was to estimate the functional status of chronic HF in patients with dilated cardiomyopathy, by investigating the changes in echo-variables, as assessed by echo-dobutamine, in relation with VO2 max.A low infusion rate echo-dobutamine test (10 micrograms/kg/min) was performed in 30 patients with dilated cardiomyopathy and 1 h later VO2 max was measured. VO2 max (ranging from 7.6 to 23 ml/kg/min, mean 14.06 +/- 0.64 ml/kg/min) was correlated with the changes (values obtained after inotropic stimulation minus those obtained at baseline) in left ventricular end-systolic diameter (r:0.80, p:0.001), in left ventricular end-systolic posterior wall thickness (r:0.73, p:0.001) and in left ventricular heart-rate corrected mean velocity of circumferential fiber shortening (Vcfc)/end-systolic meridional wall stress ratio (r:0.64, p:0.0001). A negative correlation was found between VO2 max and the changes in end-systolic meridional wall stress (r: -0.76, p:0.001). After dobutamine infusion Vcfc/systolic meridional wall stress ratio increased in patients with VO2 max > 14 ml/kg/min but decreased in patients with VO2 max < 14 ml/kg/min (0.0001 +/- 0.0001 vs -0.0002 +/- 0.0003 circ x cm2/g x s, p:0.0001). End-systolic meridional wall stress was decreased in patients with VO2 max > 14 ml/kg/min but increased in patients with VO2 max < 14 ml/kg/min (-126.97 +/- 34.24 vs 205.77 +/- 56.71 g/cm2, p:0.0001).The changes in echo-variables assessed by echo-dobutamine are well correlated with VO2 max and seem to be accurate for evaluating the functional status of chronic HF in patients with dilated cardiomyopathy.
Myocardial expression of Murf-1 and MAFbx after induction of chronic heart failure: Effect on myocardial contractility
Authors: V ADAMS, A LINKE, U WISLOFF, C DORING, S ERBS, N KRANKEL, C WITT, S LABEIT, U MULLERWERDAN, G SCHULER
Journal: Cardiovascular Research (2006)

Objective: In chronic heart failure (CHF) the myocardial expression of the inflammatory cytokine tumor necrosis factor alpha (TNF-α), which is thought to contribute to myocardial remodeling, was found to be increased. However, it is unknown whether the E3-ubiquitin ligases MAFbx and Murf-1 are involved in this remodeling process and whether their expression is regulated by TNF-α. Methods: Rats underwent ligation of the left coronary artery to induce CHF or were sham-operated. The expression of MAFbx/Murf-1 and troponin I was analyzed by RT-PCR and Western blotting in the non-infarcted area of the left ventricle. In cell culture experiments the potency of TNF-α to stimulate Murf-1/MAFbx expression, the intracellular signaling pathway, and the involvement of the E3-ligases for the impairment of contractility were assessed. Results: In CHF the myocardial expression of TNF-α was elevated 3.1-fold as compared to control. This was associated with a 4.5-fold and 2.7-fold increase in MAFbx and Murf-1 expression, respectively. A positive correlation between TNF-α and the expression of MAFbx or Murf-1 was evident. In neonatal rat cardiomyocytes, TNF-α induced the expression of MAFbx through p38MAPK-dependent pathways, whereas the induction of Murf-1 required the activation of the p42/44 MAPK pathway. Exposure of cardiomyocytes to TNF-α resulted in troponin I ubiquitinylation, subsequent degradation, and a decline in contractility. This was completely abrogated by siRNAs against Murf-1/MAFbx. Conclusion: TNF-α, which is increasingly expressed in CHF, induces troponin I degradation through a MAFbx/Murf-1-dependent pathway. This was associated with an impairment of contractility and might be one mechanism involved in the adverse remodeling process in CHF.
Modulation of secretory leukoprotease inhibitor gene expression in human bronchial epithelial cells by phorbol ester.
Authors: M Maruyama, J G Hay, K Yoshimura, C S Chu, R G Crystal
Journal: Journal of Clinical Investigation (1994)

Secretory leukoprotease inhibitor (SLPI), a 12-kD nonglycosylated serine antiprotease, helps to protect the epithelial surface of the airways from the destructive capacity of neutrophil elastase. Based on the recognition that SLPI levels can increase in the presence of airway inflammation, we hypothesized that inflammatory stimuli should modulate the expression of the SLPI gene in airway epithelial cells. To evaluate this, the modulation of SLPI gene expression with various inflammatory stimuli was evaluated in the HS-24 human bronchial epithelial cell line. After preliminary studies showed that several inflammatory mediators enhanced SLPI messenger RNA (mRNA) levels, PMA was used as a model inflammatory stimulus. PMA significantly increased the level of 0.7-kb SLPI mRNA transcripts in HS-24 cells in a dose- and time-dependent fashion and increased the amount of SLPI protein in the culture supernatant. Nuclear run-on analyses showed that the SLPI gene transcription rate increased approximately twofold after PMA stimulation. Transfection studies using fusion genes composed of fragments of up to 1.2 kb of the 5' flanking sequence of the SLPI gene and a luciferase reporter gene demonstrated potent promoter activity in the 131-bp segment (-115 to +16 relative to the transcription start site), and all longer segments up to 1.2 kb, whereas smaller segments showed low promoter activity. An 18-bp element (-98 to -115), in a region with homology to PMA-responsive regions in the Moloney murine leukemia virus enhancer and the IL-8 gene, was shown to be of importance in the level of transcription of the SLPI gene. However, this element was not responsible for the upregulation of SLPI gene expression by PMA. Evaluation of HS-24 cells in the presence of actinomycin D demonstrated that SLPI mRNA transcripts were very stable and became more so in the presence of PMA. Thus, SLPI gene expression in airway epithelial cells can be upregulated by an inflammatory stimulus, and this modulation is regulated at both the transcriptional and posttranscriptional levels. These mechanisms of SLPI upregulation likely play a role in defending the epithelial surface in the local milieu of inflammatory lung diseases.
DIRECT IMMUNOFLUORESCENT STUDY OF THE SKIN ON OCCURRENCE OF COMPLEMENT IN PEMPHIGUS
Authors: TH. JOOST, R. H. CORMANE, K. W. PONDMAN
Journal: British Journal of Dermatology (1972)

In 6 cases of pemphigus (4 pemphigus vulgaris, 1 pemphigus vegetans and 1 pemphigus erythematosus) the direct immunofluorescent method (DIF) revealed various complement factors, as there are Clq, C4 (β1E), β1A and α2D, localized in the intercellular spaces of the epidermis of the skin or mucosa immediately next to the bulla. Immunoglobulin and complement were shown together in the prickle cell layer of the epidermis, while complement staining alone usually could be shown in the intercellular spaces of basal cell layers and in the junctional zone. The possibility that antibody‐mediated complement deposition and/or alternate pathway activation may play a role in the underlying mechanism in pemphigus is discussed.
Hepatitis C virus-induced up-regulation of microRNA-155 promotes hepatocarcinogenesis by activating Wnt signaling
Authors: Yiliang Zhang, Wei Wei, Na Cheng, Kaihui Wang, Bin Li, Xiaoqing Jiang, Shuhan Sun
Journal: Hepatology (2012)

Hepatitis C virus (HCV) infection usually induces chronic hepatic inflammation, which favors the initiation and progression of hepatocellular carcinoma (HCC). Moreover, microRNA-155 (miR-155) plays an important role in regulating both inflammation and tumorigenesis. However, little is known about whether and how miR-155 provides the link between inflammation and cancer. In this study we found that miR-155 levels were markedly increased in patients infected with HCV. MiR-155 transcription was regulated by nuclear factor kappa B (NF-κB), and p300 increased NF-κB-dependent miR-155 expression. The overexpression of miR-155 significantly inhibited hepatocyte apoptosis and promoted cell proliferation, whereas miR-155 inhibition induced G(0) /G(1) arrest. Up-regulated miR-155 resulted in nuclear accumulation of β-catenin and a concomitant increase in cyclin D1, c-myc, and survivin. Gain-of-function and loss-of-function studies demonstrated that miR-155 promoted hepatocyte proliferation and tumorigenesis by increasing Wnt signaling in vitro and in vivo, and DKK1 (Wnt pathway inhibitor) overexpression inhibited the biological role of miR-155 in hepatocytes. Finally, adenomatous polyposis coli (APC), which negatively regulates Wnt signaling, was identified as the direct and functional target of miR-155.HCV-induced miR-155 expression promotes hepatocyte proliferation and tumorigenesis by activating Wnt signaling. The present study provides a better understanding of the relationship between inflammation and tumorigenesis, and thus may be helpful in the development of effective diagnosis and treatment strategies against HCV-HCC.
OC-052 Comparative evaluation of outcomes in adolescents with IBD on transfer from paediatric to adult health care services: a case for structured transition
Authors: R Cole, D Ashok, P Kumar, A Razack, A Azaz, S Sebastian
Journal: Gut (2012)

<h3>Introduction</h3> Transition and transfer of adolescent IBD patients to adult health care services is considered suboptimal in surveys. There is limited data on patients undergoing transition and transfer. We aimed to evaluate the impact of transition service on clinical and developmental outcomes of adolescent IBD patients on transfer to adult health care services. <h3>Methods</h3> We reviewed records of IBD patients diagnosed in paediatric care who has been transferred to the adult IBD service. We extracted data on their transition and transfer arrangements, disease outcomes, surgery requirements, radiation exposure, medication compliance, alcohol and drug use and growth and development. The data was compared between those who attended transition service with those who did not pass through the transition service. <h3>Results</h3> 51 patients were identified (29M and 22F). 38 patients had Crohn`s disease, 11 ulcerative colitis and two indeterminate. The median age at diagnosis was 14 years (range 9–16 years) and the median age at first visit to adult health care was 18 years.35 patients went through the transition system (group A) but 16 had no formalised transition arrangement before transfer (group B). Group A patients had a median of three appointments (range 2–7) in transition clinic before transfer. Significantly higher number of group B patients needed surgery within 2 years of transfer when compared to patients in group A (26% vs 17.1%, p=0.05). Similarly 75% of patients in group B needed at least one admission when compared to only 28.6% of group A patients (p=0.002). Non-attendance to clinics was a higher problem in group A patients with 93.75% having at least one non attendance while 37.1% of group B failed to attend at least one appointment. In addition, drug compliance rates were higher in the transition group when compared to group B (76% and 37.5% respectively p=0.001. Higher proportion of transitioned patients achieved their estimated maximum growth potential when completing adolescence. 31 of the 35 patients in group A proceeded to higher education/and or employment while this was achieved only by 50% of the group B patients. The mean cumulated IBD related radiation exposure was higher was in group B patients (17.04 mSv) when compared to group A (7.48 mSv) (p=0.0001). There was a trend towards higher dependence on opiates and smoking in group B patients. <h3>Conclusion</h3> In adolescent IBD patients, transition care is associated with better disease specific and developmental outcomes. Prospective studies of different models of transition care in IBD are needed. <h3>Competing interests</h3> None declared.
MG28, a novel fatty acid synthase inhibitor, overcomes resistance to anti-HER therapies in breast cancer.
Authors: T Puig, A Urruticoechea, G Oliveras, H Aguilar, C Turrado, S Cufí, S Ortega-Gutiérrez, B Benhamú, M López-Rodríguez, R Colomer
Journal: Cancer Research (2009)

Abstract Abstract #2143 Introduction: Resistance to anti-HER2 therapy is a common feature in Her2 positive breast cancer. The green tea polyphenol epigallocatechin 3-gallate (EGCG) is an effective antitumoral therapy through the blockade of FASN. We have developed polyphenolic compounds that inhibit FASN with greater efficacy than EGCG. Here we report the anticancer activity of MG28, one of the new synthesized FASN inhibitors, alone or in combination with trastuzumab, lapatinib, erlotinib and cetuximab in a HER-amplified breast cancer models.&amp;#x2028; Experimental design: We analysed the cytotoxic effects of MG28 alone and in combination with trastuzumab, lapatinib, erlotinib, or cetuximab in HER2+ and EGFR+ human breast cancer cells. Combinations of MG28 with targeted agents were tested for synergism, additivity and antagonism using the isobologram analysis. We further analysed changes in FASN protein levels, in apoptosis [as assessed by cleavage of poly(ADP-ribose) polymerase (PARP)], and in activation of HER2, AKT and MAPK.&amp;#x2028; Results: Combination index analysis showed synergistic cytotoxic effects of MG28 combined with trastuzumab, erlotinib or lapatinib (p &amp;lt; 0.001) and antagonic effects with cetuximab (p &amp;lt; 0.05) in HER2 overexpressing cells. MG28 plus lapatinib was significantly correlated with increased apoptosis and inhibition of phosphorilated HER2 and MAPK. Response to co-exposure of MG28 plus erlotinib was significantly correlated with increased apoptosis and its ability to inhibit HER2, MAPK and AKT phosphorilation. HER2+ cells showed partial resistance to trastuzumab and combined treatment of trastuzumab with MG28 reversed significantly this resistance and thus correlated with increasing cleavage of PARP and its ability to inhibit phosphorylation of HER2 and AKT.&amp;#x2028; Conclusion: FASN inhibition seems to be an effective approach to overcome resistance to anti- HER therapies. Our results provide a new therapeutic strategy for further in vivo – combined treatments using drugs that target HER2, EGFR and FASN. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2143.
YC-1 Induces S Cell Cycle Arrest and Apoptosis by Activating Checkpoint Kinases
Authors: Eun-Jin Yeo, Ji-Hye Ryu, Yang-Sook Chun, Young-Suk Cho, In-Jin Jang, HoSung Cho, Jinho Kim, Myung-Suk Kim, Jong-Wan Park
Journal: Cancer Research (2006)

Abstract Hypoxia-inducible factor-1α (HIF-1α) seems central to tumor growth and progression because it up-regulates genes essential for angiogenesis and the hypoxic adaptation of cancer cells, which is why HIF-1α inhibition is viewed as a cancer therapy strategy. Paradoxically, HIF-1α also leads to cell cycle arrest or the apoptosis of cancer cells. Thus, the possibility cannot be ruled out that HIF-1α inhibitors unlock cell cycle arrest under hypoxic conditions and prevent cell death, which would limit the anticancer effect of HIF-1α inhibitors. Previously, we reported on the development of YC-1 as an anticancer agent that inhibits HIF-1α. In the present study, we evaluated the effects of YC-1 on hypoxia-induced cell cycle arrest and cell death. It was found that YC-1 does not reverse the antiproliferative effect of hypoxia, but rather that it induces S-phase arrest and apoptosis at therapeutic concentrations that inhibit HIF-1α and tumor growth; however, YC-1 did not stimulate cyclic guanosine 3′,5′-monophosphate production in this concentration range. It was also found that YC-1 activates the checkpoint kinase–mediated intra-S-phase checkpoint, independently of ataxia-telangiectasia mutated kinase or ataxia-telangiectasia mutated and Rad3-related kinase. These results imply that YC-1 does not promote the regrowth of hypoxic tumors because of its cell cycle arrest effect. Furthermore, YC-1 may induce the combined anticancer effects of HIF-1α inhibition and cell growth inhibition. (Cancer Res 2006; 66(12): 6345-52)
DERMATITIS DUE TO A CASE-HARDENING COMPOUND
Authors: G. P. B. WHITWELL
Journal: British Journal of Dermatology (1945)

Journal Article DERMATITIS DUE TO A CASE‐HARDENING COMPOUND Get access G. P. B. WHITWELL, M.D. G. P. B. WHITWELL, M.D. Works Medical Officer Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 57, Issue 9-10, 1 September 1945, Pages 169–171, https://doi.org/10.1111/j.1365-2133.1945.tb11224.x Published: 01 September 1945
Tumor Necrosis Factor-α Induces Fibronectin Synthesis in Coronary Artery Smooth Muscle Cells by a Nitric Oxide–Dependent Posttranscriptional Mechanism
Authors: Catherine A. E. O’Blenes, Caroline Kinnear, Marlene Rabinovitch
Journal: Circulation Research (2001)

Postcardiac transplant coronary arteriopathy is associated with tumor necrosis factor-alpha (TNF-alpha) induction of fibronectin-dependent smooth muscle cell (SMC) migration into the subendothelium, resulting in occlusive neointimal formation. Because expression of inducible nitric oxide synthase (iNOS) is elevated in neointimal formation after transplantation and upregulated in vascular SMCs by TNF-alpha, we investigated whether TNF-alpha induction of fibronectin synthesis in coronary artery (CA) SMCs is mediated by nitric oxide (NO). TNF-alpha caused a dose-dependent increase in reactive oxygen and nitrogen intermediates in CA SMCs (P<0.05). This correlated with increased NO production (P<0.05) and fibronectin synthesis (P<0.05). TNF-alpha induction of fibronectin synthesis was abrogated by the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA) (P<0.05) or the flavonoid-containing enzyme inhibitor diphenyleneiodonium (DPI) (P<0.05) and reproduced with the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) (P<0.05). Northern blotting showed no effect of TNF-alpha on steady-state fibronectin mRNA levels. TNF-alpha increased expression of light chain 3 (LC-3), a protein shown previously to facilitate fibronectin mRNA translation through its interaction with an adenosine-uracil rich element (ARE) in the 3'-untranslated region of fibronectin mRNA. RNA gel mobility shift and UV cross-linking assays using CA SMC lysates revealed protein binding complexes with radiolabeled oligonucleotide containing the ARE, similar to those generated with recombinant LC-3. One of these complexes increased after TNF-alpha treatment, an effect inhibited with L-NMMA or DPI. These data demonstrate a novel paradigm whereby cytokines regulate mRNA translation of extracellular matrix proteins through NO-dependent modulation of RNA binding protein interaction with mRNA.