tbuckley/cabot-search huggingface dataset:
Cardiovascular Function in Acromegaly
Authors: R. N. Clayton
Journal: Endocrine Reviews (2003)

Even with modern treatment, acromegaly is associated with a 2-to 3-fold increase in mortality, mainly from vascular disease, which is probably a result of the long exposure of tissues to excess GH before diagnosis and treatment.There is accumulating evidence that effective treatment to lower serum GH levels to less than 1-2 ng/ml (glucose suppressed or random, respectively) and normalize IGF-I improves long-term outcome and survival.In addition to recognized cardiovascular risk factors of hypertension, type 2 diabetes mellitus, and dyslipidemia, there is accumulating evidence of specific structural and functional changes in the heart in acromegaly.Along with endothelial dysfunction, these changes may contribute to the increased mortality in this disease.There are specific structural changes in the myocardium with increased myocyte size and interstitial fibrosis of both ventricles.Left ventricular hypertrophy is common even in young patients with short duration of disease.Some of these structural changes can be reversed by effective treatment.Functionally, the main consequence of these changes is impaired left ventricular diastolic function, particularly when exercising, such that exercise tolerance is reduced.Diastolic function im-proves with treatment, but the effect on exercise tolerance is more variable, and more longitudinal data are required to assess the benefits.What scant data there are on rhythm changes suggest an increase in complex ventricular arrhythmias, possibly as a result of the disordered left ventricular architecture.The functional consequences of these changes are unclear, but they may provide a useful early marker for the ventricular remodeling that occurs in the acromegalic heart.Endothelial dysfunction, especially flow-mediated dilatation, is an early marker of atherosclerosis, and limited data imply that this is impaired in active acromegaly and can be improved with treatment.Similarly, early arterial structural changes, such as thickened intima media layer, appear more common in acromegalics, and there are hints that this may diminish with effective treatment, although more studies are required for a definite conclusion on this topic.In conclusion, impaired cardiac and endothelial structure and function in acromegaly are risk factors for vascular mortality and should be regarded as legitimate therapeutic targets in the overall management of this condition.(Endocrine Reviews 24: 272-277, 2003) I. Introduction-Increased Mortality in Acromegaly II.Cardiomyopathy in Acromegaly III.Functional Changes in the Acromegalic Heart IV.Cardiac Dysrhythmias in Acromegaly V.The Endothelium in Acromegaly VI. Conclusions
Increase in Influenzal Meningitis
Authors: Richard H. Michaels
Journal: New England Journal of Medicine (1971)

AN increase in Haemophilus influenzae meningitis admissions has occurred at the Children's Hospital of Pittsburgh during the past three decades. No evidence has been found that it is due to increased referral to this hospital, improved laboratory methods or change in age distribution.There has been a rise of approximately 50 per cent in total admissions during the past 25 years. The increase in admissions due to H. influenzae meningitis, however, has been much greater: over 400 per cent during the same period (Fig. 1). There has been no appreciable change in admissions lor meningitis due to Diplococcus pneumoniae, . . .
HCC Is promoted by bacterial translocation and TLR-4 signaling: A new paradigm for chemoprevention and management
Authors: Sara Toffanin, Helena Cornella, Andrew Harrington, Josep M. Llovet, Roberto J. Groszmann, Yasuko Iwakiri, Tamar H. Taddei
Journal: Hepatology (2012)

Abstract Increased translocation of intestinal bacteria is a hallmark of chronic liver disease and contributes to hepatic inflammation and fibrosis. Here we tested the hypothesis that the intestinal microbiota and Toll-like receptors (TLRs) promote hepatocellular carcinoma (HCC), a long-term consequence of chronic liver injury, inflammation, and fibrosis. Hepatocarcinogenesis in chronically injured livers depended on the intestinal microbiota and TLR4 activation in non-bone-marrow-derived resident liver cells. TLR4 and the intestinal microbiota were not required for HCC initiation but for HCC promotion, mediating increased proliferation, expression of the hepatomitogen epiregulin, and prevention of apoptosis. Gut sterilization restricted to late stages of hepatocarcinogenesis reduced HCC, suggesting that the intestinal microbiota and TLR4 represent therapeutic targets for HCC prevention in advanced liver disease.
Experimental transmission of an autosomal dominant spongiform encephalopathy: does the infectious agent originate in the human genome?
Authors: H F Baker, R M Ridley, T J Crow
Journal: BMJ (1985)

Marmosets inoculated intracerebrally with brain tissue from a woman with Gerstmann-Straussler syndrome (an autosomal dominant dementia associated with spongiform change and amyloid deposition) developed an encephalopathy indistinguishable from that seen in marmosets inoculated with brain tissue from a typical case of Creutzfeldt-Jakob disease. As in Huntington's disease, in the pedigree of the patient with Gerstmann-Straussler syndrome women who subsequently developed the illness had increased fecundity. The pathogen in human transmissible dementia may arise from a sequence (which itself sometimes confers a selective advantage) located within the human genome.
Private Methadone Maintenance
Authors: Arthur Zaks
Journal: JAMA (1972)

In the first year of operation of a private methadone maintenance program, patients made significant gains in social and vocational rehabilitation. The percentage of patients staying in the treatment program is similar to that for public programs. Patients expressed feelings of responsibility in providing for their own medical treatment. Methadone maintenance on a fee-for-service basis is a feasible method for providing this treatment. Government money is more efficiently spent in monitoring private facilities than in direct subsidy of public programs.
Infarcts after surgery
Authors: N Mamode, S Cobbe, J G Pollock
Journal: BMJ (1995)

Decisions about the cardiac risk of a surgical procedure may be taken by the surgeon, anaesthetist, cardiologist, referring doctor, or general practitioner. All need to make informed judgments about the perioperative risk, yet despite advances in anaesthesia and surgical techniques the prediction of risk remains an uncertain science.

The leading cause of death after surgery is myocardial infarction.1 Non-fatal myocardial infarction accounts for considerable morbidity2; it may be silent in a quarter of cases, and (not surprisingly) it is associated with a poor outcome. Yet 17 years after Goldman et al developed a clinical risk score in an attempt to predict which patients would develop cardiac complications3 we are not aware of any prospective trial in Britain intended to measure the incidence of perioperative infarction. Trials in North America have reported rates of serious cardiac complications ranging from 1.7% to 40%.4 These data have been used to justify strategies as various as no attempt at predicting risk and routine preoperative coronary angiography in high risk subsets such as patients with peripheral vascular disease.5 Assessment of the extent of …
Persistent vegetating and keratotic lesions in patients with pemphigus vulgaris during immunosuppressive therapy
Authors: W.R. FABER, H.A.M. NEUMANN, J. FLINTERMAN
Journal: British Journal of Dermatology (1983)

Journal Article Persistent vegetating and keratotic lesions in patients with pemphigus vulgaris during immunosuppressive therapy Get access W.R. FABER, W.R. FABER Ziekenhuis ‘De Lichtenberg’, Department of Dermatology, Amersfoort, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar H.A.M. NEUMANN, H.A.M. NEUMANN St, Lambertus Ziekenhuis, Department of Dermatology, Helmond, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar J. FLINTERMAN J. FLINTERMAN Ziekenhuis ‘De Lichtenberg’, Department of Dermatology, Amersfoort, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 109, Issue 4, 1 October 1983, Pages 459–463, https://doi.org/10.1111/j.1365-2133.1983.tb04621.x Published: 01 October 1983 Article history Accepted: 31 January 1983 Published: 01 October 1983
CHRONIC EPIDEMIC ENCEPHALITIS
Authors: WALTER FREEMAN
Journal: JAMA (1926)

The continued prevalence of epidemic encephalitis both in this country and in Europe has given rise to grave misgivings concerning the future ravages of the disease. Especially in England, where more than 5,000 cases were reported in 1924, 1 there is no little concern. The disease seems to be on the increase, and several small epidemics have been reported in this country.  Were this a simple febrile disease, even as severe as scarlet fever, its prevalence would cause little comment. Such a disease runs its course and after the attack the survivor is usually well and immune to future attacks. In the case of encephalitis, however, we are dealing with a different order of things. The initial mortality is more than 30 per cent. As if that were not bad enough, some 70 per cent 2 of those that recover from the acute attack show various disease manifestation ranging from
TR-07 * LB100, A NOVEL PROTEIN PHOSPHATASE 2A INHIBITOR, ENHANCES CISPLATIN AND RADIATION MEDIATED CYTOTOXICITY AND OVERCOME CISPLATIN RESISTANCE IN-VITRO
Authors: S. C. W. Ho, M. Feldman, D. Maric, J. Heiss, Z. Zhuang
Journal: Neuro-Oncology (2015)

INTRODUCTION: Medulloblastoma is the most common malignant brain tumors. Current therapeutic strategies combining surgery, chemotherapy and radiation offer high survival rate but confer significant treatment-related comorbidity. LB100, a novel small molecule Protein Phosphatase 2A (PP2A) inhibitor, has demonstrated efficacy in a number of non-intracranial tumors. The objective of this study is to assess LB100 effectiveness for treatment of medulloblastoma. METHODS: Experiments were performed using DAOY and D341-MED cell lines: XTT assay was performed to assess for cell viability, immunohistochemistry was performed to assess for DNA double-strand breaks and mitotic catastrophe using gamma H2X and alpha tubulin staining respectively. Flow cytometry was performed for cell cycle analysis. A cisplatin - resistant D341 cell line was developed by constant exposure to escalating concentration of cisplatin (up to 4 uM) resulting in a stably resistant cell line with 8-fold increases in IC50. RESULTS: LB100 enhances cisplatin-mediated cytotoxicity. XTT assay showed the IC50 of cisplatin decreased from ∼7uM to < 2uM and from ∼3uM to <0.5 uM with 5uM LB100 in DAOY and D341 respectively after 48 hours of drug exposure. In DAOY, LB100 enhances radiation induced DNA double-strand breaks with ∼5 fold increase in gamma H2X foci and ∼4 fold increase in proportion of cells undergoing mitotic catastrophe on immunohistochemistry with 5uM LB100. In D341, cell cycle analysis demonstrates ∼ 2 fold increase in percentage of cells in G2/M with 10uM LB100 consistent with increased mitotic catastrophe. There is no difference in sensitivity to increasing concentration of LB100 between wide-type D341 and cisplatin resistant D341 on cell viability suggesting that LB100 has equal potency against wild type and cisplatin resistant cell line. CONCLUSIONS: LB100 treatment is an effective radiation and chemotherapy sensitizing agent in-vitro. Further in-vivo study will provide the preclinical data needed to consider LB100 as an adjuvant agent for treatment of medulloblastoma.
Mortality of male doctors and reductions in cigarette smoking.
Authors: T Khosla, H Campbell
Journal: BMJ (1980)

problems, and deafness,9 10 as well as sudden infant death."112The task of clearing the population of potentially dangerous viruses before immuni- sation may well prove impossible; but does that justify our setting up ill-founded contra- indications, rather than real ones, and then shooting them down in order to prove that our vaccines are safe ?
Dietary Fiber — Nostrum or Critical Nutrient?
Authors: William E. Connor
Journal: New England Journal of Medicine (1990)

For almost a generation, dietary fiber has been a household word and has carried a remarkably persuasive aura of disease prevention. Both the public and cereal companies have taken up dietary fiber with great enthusiasm. Consumers can now rate breakfast cereals by the amount of fiber listed on the box and take particular note if the cereal contains oat bran, a source of soluble fiber thought to be of particular merit. What is truth and what is fiction about dietary fiber?Fiber is present in all plant foods that have had no more than a minimum of processing. Thus, our . . .
A8.34 CD1C + dendritic cells are overrepresented in lymph nodes of early arthritis patients and related to B cell responses
Authors: T H Ramwadhdoebe, L G M van Baarsen, F H Berger, M Maas, D M Gerlag, P P Tak, M C Lebre
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> The immune system is composed of different cell populations that circulate in our body through lymphoid organs. We have recently shown that the numbers of CD69<sup>+</sup> T cells and B cells are increased in lymph node (LN) biopsies from early arthritis patients. DCs are fundamental in initiating and modulating T and B cell responses and may therefore play an essential pathologic role in autoimmune diseases. We hypothesize that an in-depth analysis of DCs within LNs of at risk individuals and early arthritis patients can provide a better understanding of immune function and dysregulation during the earliest phases of arthritis. <h3>Materials and Methods</h3> We included 22 individuals with arthralgia without any evidence of arthritis who were positive for IgM rheumatoid factor and/or anti-citrullinated protein antibodies (ACPA; RA risk group), 20 DMARD and biological naïve early arthritis patients (2010 criteria &lt; 1 year) and 8 seronegative control individuals. All study subjects underwent ultrasound-guided inguinal LN biopsy. DC subsets (CD1a, CD1c, and CD304) were analysed by multi-colour flow cytometry. <h3>Results</h3> All DC subsets included in this study could be detected in LN biopsies. However, CD1c<sup>+</sup> DC were the major subset present in LNs of early arthritis patients compared to both CD304<sup>+</sup> DCs (p &lt; 0.0001) or CD1a<sup>+</sup> DCs (p &lt; 0.002). In line with this, there was a significant increase of CD1c<sup>+</sup> DCs in the early arthritis group compared to the at risk group (p = 0.009) and compared to control individuals (p = 0.01). Moreover, in early arthritis patients the frequencies of CD1c<sup>+</sup> DCs were significantly increased in ACPA<sup>+</sup> compared to ACPA<sup>-</sup> patients (p = 0.03). The frequencies of CD304<sup>+</sup> DC were also significantly increased in early arthritis compared to the at risk group (p = 0.009) but did not correlate with ACPA status. <h3>Conclusions</h3> This is the first study that reports the presence of DC subsets in LNs during the earliest phases of arthritis. As CD1c<sup>+</sup> DCs are the main DC subset present in early arthritis and the only subset related with ACPA status, this study supports the notion that in addition to the well-known capacity of CD1c<sup>+</sup> DCs to activate naïve T cells, CD1c<sup>+</sup> DC might also contribute to B cell responses.
Herpes Simplex Virus Encephalitis
Authors: Sam U. Ho
Journal: JAMA (1982)

Herpesviruses capable of causing human neurological disease include herpes simplex, varicella-zoster, cytomegalovirus, and the Epstein-Barr (EB) virus. They are DNA viruses that contain a glycolipid envelope and replicate in the nucleus of the host cell. Members of this group share the property of causing primary (initial) infection and subsequent reactivation of latent infections. There are two serological strains of herpes simplex virus (HSV). The type 1 strains (HSV-1) cause almost all cases of herpes simplex encephalitis and meningitis in adults. Infections with the type 2 strains (HSV-2) occur as a vesicular eruption on genital mucosa, transmitted by sexual contact. Also associated with HSV-2 are disseminated disease of the newborn and occasional cases of viral meningitis in adults. Type 1 HSV is the single most important cause of fatal sporadic encephalitis in the United States and England. All age groups are affected, and there is no seasonal predominance of incidence. In
Chronic memory impairment after cardiac arrest outside hospital
Authors: N. R Grubb, R. O'Carroll, S. M Cobbe, J. Sirel, K. A A Fox
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objectives</b>: To evaluate the nature, prevalence, and severity of chronic memory deficit in patients resuscitated after cardiac arrest outside hospital and to determine whether such deficits are related to duration of cardiac arrest. <b>Design</b>: Case-control study. <b>Subjects</b>: 35 survivors of cardiac arrest outside hospital and 35 controls matched for age and sex who had had acute myocardial infarction without cardiac arrest. <b>Main outcome measures</b>: Subjects assessed at least two months after index event for affective state (hospital anxiety and depression scale), premorbid intelligence (national adult reading test), short term recall (digit recall test), and episodic long term memory (Rivermead behavioural memory test). <b>Results</b>: Cases and controls showed no difference in short term recall. Cases scored lower on Rivermead test than controls (mean (SD) score out of 24 points: 17.4 (5.4) v 21.8 (2.0), P&lt;0.001), particularly in subtests relating to verbal and spatial memory. Moderate or severe impairment was found in 37% of cases and in no controls. Severity of impairment of memory correlated significantly with measures of duration of cardiac arrest. This deficit was not significantly associated with subjects9 age, interval from index event to assessment, occupation, measures of comorbidity, social deprivation, anxiety or depression scores, or estimated premorbid intelligence. <b>Conclusions</b>: Clinically important impairment of memory was common after cardiac arrest outside hospital. Improvement in response times of emergency services could reduce the severity of such deficits. With an increasing numbers of people expected to survive cardiac arrest outside hospital, rehabilitation of those with memory deficit merits specific attention. <h3>Key messages</h3> In this study of 35 such patients we found that over a third had important chronic deficits in long term memory, though orientation and short term memory were unimpaired Memory scores were inversely correlated with the duration of the cardiac arrest, suggesting that improvement of emergency services9 response times might result in better cognitive outcomes Targeted rehabilitation strategies could train patients to make the best use of their remaining memory function Assessment of cognitive function is an important component of patients9 man- agement after discharge from hospital
Marihuana Smoking
Authors: Peter Beaconsfield, Jean Ginsburg, Rebecca Rainsbury
Journal: New England Journal of Medicine (1972)

Marihuana smoking by subjects without previous experience causes an increase in limb blood flow concomitantly with a rise in pulse rate. These responses are still evoked after administration of atropine but not after pretreatment with propranolol, a beta-adrenergic blocker. The tachycardias of atropine and of epinephrine are potentiated by marihuana. These findings suggest that the increase in pulse rate and peripheral blood flow induced by cannabis involves beta-adrenergic vascular mechanisms, and counsel caution in the administration of vasoactive drugs and anesthetics for those who may have been smoking marihuana.
Evidence That Links Loss of Cyclooxygenase-2 With Increased Asymmetric Dimethylarginine
Authors: Blerina Ahmetaj-Shala, Nicholas S. Kirkby, Rebecca Knowles, Malak Al’Yamani, Sarah Mazi, Zhen Wang, Arthur T. Tucker, Louise Mackenzie, Paul C. J. Armstrong, Rolf M. Nüsing, James A. P. Tomlinson, Timothy D. Warner, James Leiper, Jane A. Mitchell
Journal: Circulation (2014)

Cardiovascular side effects associated with cyclooxygenase-2 inhibitor drugs dominate clinical concern. Cyclooxygenase-2 is expressed in the renal medulla where inhibition causes fluid retention and increased blood pressure. However, the mechanisms linking cyclooxygenase-2 inhibition and cardiovascular events are unknown and no biomarkers have been identified.Transcriptome analysis of wild-type and cyclooxygenase-2(-/-) mouse tissues revealed 1 gene altered in the heart and aorta, but >1000 genes altered in the renal medulla, including those regulating the endogenous nitric oxide synthase inhibitors asymmetrical dimethylarginine (ADMA) and monomethyl-l-arginine. Cyclo-oxygenase-2(-/-) mice had increased plasma levels of ADMA and monomethyl-l-arginine and reduced endothelial nitric oxide responses. These genes and methylarginines were not similarly altered in mice lacking prostacyclin receptors. Wild-type mice or human volunteers taking cyclooxygenase-2 inhibitors also showed increased plasma ADMA. Endothelial nitric oxide is cardio-protective, reducing thrombosis and atherosclerosis. Consequently, increased ADMA is associated with cardiovascular disease. Thus, our study identifies ADMA as a biomarker and mechanistic bridge between renal cyclooxygenase-2 inhibition and systemic vascular dysfunction with nonsteroidal anti-inflammatory drug usage.We identify the endogenous endothelial nitric oxide synthase inhibitor ADMA as a biomarker and mechanistic bridge between renal cyclooxygenase-2 inhibition and systemic vascular dysfunction.
Abstract 665: Targeting the MluI cell cycle box (MCB) sequence 5’-ACGCGT-3’ in the human Dbf4 promoter using the rationally designed polyamide formamido-imidazole-pyrrole-imidazole (f-IPI)
Authors: Shicai Lin, Konstantinos Kiakos, Moses Lee, Daniel Hochhauser, John A. Hartley
Journal: Cancer Research (2011)

Abstract Dbf4 is the regulatory subunit of Cdc7 kinase, which is essential for the initiation of DNA replication throughout S-phase. The level of Dbf4 is critical for the activation of Cdc7. Human Cdc7/Dbf4 (HuCdc7/Dbf4) kinase activity is essential for cell proliferation by activating DNA replication. High levels of the Cdc7 kinase activity have been implicated with a large number of aggressive solid cancers. The MluI cell cycle box (MCB) sequence 5’-ACGCGT-3’ is the critical site for transcription factor binding that activates the expression of the HuCdc7/Dbf4 core gene in mammalian cells. HuDbf4 promoter activity has previously been shown to be significantly reduced by a point mutation within the MCB. We have previously shown that the rationally designed simple polyamide formamido-imidazole-pyrrole-imidazole (f-IPI) binds to its cognate sequence 5’-ACGCGT-3’ as a stacked dimer in an anti-parallel conformation (2:1 ligand/DNA complex) with exceptionally high affinity and selectivity, superior to the natural product distamycin A binding to its cognate sequence. DNAse I footprinting experiments indicated selective binding of f-IPI to the MCB sequence in the HuDbf4 promoter at 0.1µM. Eletrophoretic mobility shift assays using the MCB-containing sequence from the HuDbf4 promoter showed dose-dependent inhibition of protein binding by f-IPI which was complete at 0.5µM. RT-PCR showed decreased expression of HuDbf4 mRNA in response to incubation of exponentially growing MDA-MB231 cells with 10 μM f-IPI. Selective effects on protein expression, DNA replication and cell cycle are currently underway. These data demonstrate the potential of small molecule polyamides as modulators of gene expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 665. doi:10.1158/1538-7445.AM2011-665