tbuckley/cabot-search huggingface dataset:
Periostin promotes liver steatosis and hypertriglyceridemia through downregulation of PPARα
Authors: Yan Lu, Xing Liu, Yang Jiao, Xuelian Xiong, E Wang, Xiaolin Wang, Zhijian Zhang, Huijie Zhang, Lingling Pan, Youfei Guan, Dongsheng Cai, Guang Ning, Xiaoying Li
Journal: Journal of Clinical Investigation (2014)

Hepatosteatosis is characterized by an aberrant accumulation of triglycerides in the liver; however, the factors that drive obesity-induced fatty liver remain largely unknown. Here, we demonstrated that the secreted cell adhesion protein periostin is markedly upregulated in livers of obese rodents and humans. Notably, overexpression of periostin in the livers of WT mice promoted hepatic steatosis and hypertriglyceridemia. Conversely, both genetic ablation of periostin and administration of a periostin-neutralizing antibody dramatically improved hepatosteatosis and hypertriglyceridemia in obese mice. Overexpression of periostin resulted in reduced expression of peroxisome proliferator-activated receptor α (PPARα), a master regulator of fatty acid oxidation, and activation of the JNK signaling pathway. In mouse primary hepatocytes, inhibition of α6β4 integrin prevented activation of JNK and suppression of PPARα in response to periostin. Periostin-dependent activation of JNK resulted in activation of c-Jun, which prevented RORα binding and transactional activation at the Ppara promoter. Together, these results identify a periostin-dependent pathway that mediates obesity-induced hepatosteatosis.
Effect of home based HIV counselling and testing intervention in rural South Africa: cluster randomised trial
Authors: T. Doherty, H. Tabana, D. Jackson, R. Naik, W. Zembe, C. Lombard, S. Swanevelder, M. P. Fox, A. Thorson, A. M. Ekstrom, M. Chopra
Journal: BMJ (2013)

<b>Objective</b> To assess the effect of home based HIV counselling and testing on the prevalence of HIV testing and reported behavioural changes in a rural subdistrict of South Africa. <b>Design</b> Cluster randomised controlled trial. <b>Setting</b> 16 communities (clusters) in uMzimkhulu subdistrict, KwaZulu-Natal province, South Africa. <b>Participants</b> 4154 people aged 14 years or more who participated in a community survey. <b>Intervention</b> Lay counsellors conducted door to door outreach and offered home based HIV counselling and testing to all consenting adults and adolescents aged 14-17 years with guardian consent. Control clusters received standard care, which consisted of HIV counselling and testing services at local clinics. <b>Main outcome measures</b> Primary outcome measure was prevalence of testing for HIV. Other outcomes were HIV awareness, stigma, sexual behaviour, vulnerability to violence, and access to care. <b>Results</b> Overall, 69% of participants in the home based HIV counselling and testing arm versus 47% in the control arm were tested for HIV during the study period (prevalence ratio 1.54, 95% confidence interval 1.32 to 1.81). More couples in the intervention arm had counselling and testing together than in the control arm (2.24, 1.49 to 3.03). The intervention had broader effects beyond HIV testing, with a 55% reduction in multiple partners (0.45, 0.33 to 0.62) and a stronger effect among those who had an HIV test (0.37, 0.24 to 0.58) and a 45% reduction in casual sexual partners (0.55, 0.42 to 0.73). <b>Conclusions</b> Home based HIV counselling and testing increased the prevalence of HIV testing in a rural setting with high levels of stigma. Benefits also included higher uptake of couple counselling and testing and reduced sexual risk behaviour. <b>Trial registration</b> Current Controlled Trials ISRCTN31271935.
PRESSURE ON THE GLOBE AFTER CATARACT EXTRACTION.Read in the Section on Ophthalmology, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C. May, 1891.
Authors: EDWARD JACKSON
Journal: JAMA (1891)

What is to be said under this head will also apply to all operations involving the section of the cornea or sclero-corneal junction; but is of greatest importance with reference to cataract extraction since it involves the most extensive of these sections. In the normal eye the contents of the sclero-corneal coat press outward at every point with a force represented by a column of mercury about thirty millimetres in height; and the sclero-corneal coat at every point successfully withstands this pressure, by its own continuity and firm structure. The instant a corneal section is made by the solution in the continuity of the coat its power of resisting outward pressure is annihilated. But as the same section also permits the contents of the globe to freely escape, the outward pressure is annihilated and thus a new and equally perfect equilibrium is established. My plea is that we shall respect
A funny kind of flu
Authors: Hyman Davies
Journal: BMJ (2006)

One Monday morning in the winter of 1958 I woke up to discover that the flu epidemic that had been wreaking havoc in Asia was spreading across Europe and had reached our shores; so it was with a great deal of trepidation that I made my way to the surgery to have my worst fears confirmed. My partners and I shared the colossal visiting lists, my own allocation consisted of more than 30 calls. The morning surgeries were rushed through as …
Laughter and MIRTH (Methodical Investigation of Risibility, Therapeutic and Harmful): narrative synthesis
Authors: R. E. Ferner, J. K. Aronson
Journal: BMJ (2013)

<b>Objective</b> To review the beneficial and harmful effects of laughter. <b>Design</b> Narrative synthesis. <b>Data sources and review methods</b> We searched Medline (1946 to June 2013) and Embase (1974 to June 2013) for reports of benefits or harms from laughter in humans, and counted the number of papers in each category. <b>Results</b> Benefits of laughter include reduced anger, anxiety, depression, and stress; reduced tension (psychological and cardiovascular); increased pain threshold; reduced risk of myocardial infarction (presumably requiring hearty laughter); improved lung function; increased energy expenditure; and reduced blood glucose concentration. However, laughter is no joke—dangers include syncope, cardiac and oesophageal rupture, and protrusion of abdominal hernias (from side splitting laughter or laughing fit to burst), asthma attacks, interlobular emphysema, cataplexy, headaches, jaw dislocation, and stress incontinence (from laughing like a drain). Infectious laughter can disseminate real infection, which is potentially preventable by laughing up your sleeve. As a side effect of our search for side effects, we also list pathological causes of laughter, among them epilepsy (gelastic seizures), cerebral tumours, Angelman's syndrome, strokes, multiple sclerosis, and amyotrophic lateral sclerosis or motor neuron disease. <b>Conclusions</b> Laughter is not purely beneficial. The harms it can cause are immediate and dose related, the risks being highest for Homeric (uncontrollable) laughter. The benefit-harm balance is probably favourable. It remains to be seen whether sick jokes make you ill or jokes in bad taste cause dysgeusia, and whether our views on comedians stand up to further scrutiny.
Analysis of prevalence of HIV-1 drug resistance in primary infections in the United Kingdom
Authors: None UK Collaborative Group on Monitoring the Transmission of HIV Drug Resistance
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objectives:</b> To identify changes since 1994 in the prevalence of resistance to anti-HIV drugs in primary HIV-1 infections in the United Kingdom. <b>Design:</b> Retrospective and prospective assessment of viruses obtained from people recently infected with HIV. <b>Setting:</b> Multiple centres (patients enrolled in the UK register of seroconverters) and a single large HIV clinic (active case ascertainment). <b>Participants:</b> 69 patients infected with HIV between June 1994 and August 2000. <b>Main outcome measures:</b> Prevalence of key mutations associated with drug resistance in the reverse transcriptase and protease genes of HIV-1, by year of infection. <b>Results:</b> Between June 1994 and August 2000, 10 (14%) of 69 newly infected patients had one or more key HIV-1 mutations associated with drug resistance. The risk of being infected with drug resistant virus increased over time (adjusted relative risk per year 1.74 (95% confidence interval 0.93 to 3.27), P=0.06). The estimated prevalence of drug resistance in those infected in 2000 was 27% (12% to 48%). <b>Conclusions:</b> Transmission of drug resistant HIV-1 in the United Kingdom seems to be increasing. New approaches to encourage safer sexual behaviour in all sectors of the population are urgently needed. <h3>What is already known on this topic</h3> The emergence of HIV drug resistance in patients receiving antiretroviral therapy is common Transmission of virus variants resistant to anti-HIV drugs has been documented <h3>What this paper adds</h3> The prevalence of transmitted HIV drug resistance in the United Kingdom is increasing, exceeding 20% in 2000 New approaches to encourage safer sexual behaviour are urgently needed
Subcutaneous Radionuclide Venography
Authors: MING-FENG CHEN, CHUNG-CHIENG WU, SHIANG-BIN JONG
Journal: Clinical Nuclear Medicine (1994)

Traditional acupuncture points K-3 are physiologically tender points located halfway between the Achilles tendon and the medial malleolus. Recently, the authors developed a new method of radionuclide venography of the lower limbs, namely subcutaneous radionuclide venography (SC-RNV), by subcutaneous injection of Tc-99m pertechnetate at these points. The authors applied this method in a patient with suspected deep vein thrombosis of both lower limbs. For comparison, ascending radionuclide venography by intravenous injection (IV-RNV) of Tc-99m MAA and color Doppler ultrasound were also done. The SC-RNV showed partial obstruction of right popliteal vein and complete obstruction of the left popliteal vein with prominent collateral flows. These results were compatible with the findings of color Doppler ultrasound. However, the IV-RNV showed small narrowing with patency of the left popliteal vein, and normal flow on the right. This suggests that the results of SC-RNV may be different from that of IV-RNV. The benefits of SC-RNV in the detection of deep vein thrombosis are described.
Evidence that regression in Keratoacanthoma is immunologically mediated: a comparison with squamous cell carcinoma
Authors: A. PATEL, G.M. HALLIDAY, B.E. COOKE, R.StC. BARNETSON
Journal: British Journal of Dermatology (1994)

Recent research observations suggest that the keratoacanthoma (KA) is a form of resolving squamous cell carcinoma (SCC). The mechanism by which this resolution takes place has not been fully explored, although it may have an immunological basis. To investigate this, we compared 15 clinically and histologically diagnosed KAs and 15 SCCs with regard to cellular infiltrate and keratin expression. We found that KAs have significantly higher numbers of CD3+ and CD4+ cells invading their epidermal component than SCCs. The lymphocytes infiltrating KAs were more immunologically active, as greater numbers expressed the interleukin‐2 receptor (IL‐2R) than those in SCCs. It is of interest that CD36 was expressed by a significantly greater proportion of tumour cells within KAs than SCCs. This was also the case for the intercellular adhesion molecule ICAM‐1, and the differentiation marker keratin 10. Overall, these findings suggest that KA regression is immunologically mediated, with activated (IL‐2R+) CD4+ T lymphocytes and adhesion molecules playing a pivotal role in the immune response.
Basal ganglia and movement disorders: an update
Authors: M Chesselet
Journal: Trends in Neurosciences (1996)

A model of basal ganglia functioning proposed a few years ago suggests that increased and decreased activity in basal ganglia output to the thalamus underlies akinesia, as seen in Parkinson's disease, and dyskinetic movements as seen in Huntington's disease or after treatment with l-dopa and neuroleptics, respectively. Although the basic features of this model have stood the test of time, patterns of electrophysiological activity and changes in indices of GABA-dependent transmission in the external pallidum lead to a reconsideration of the mechanisms responsible for these changes in output activity. Trends Neurosci. (1996) 19, 417–422
Efficacy and mode of action of hammerhead and hairpin ribozymes against various HIV-1 target sites
Authors: Graham Hotchkiss, Catharina Maijgren-Steffensson, Lars Ährlund-Richter
Journal: Molecular Therapy (2004)

Ribozymes have been proposed as gene therapy agents against HIV-1, although many fundamental questions about their mechanism of action remain unclear. Few studies have compared directly the potential of different modified ribozyme species against a particular target. Here we compare the relative abilities of hammerhead (HhU5) and hairpin (HpU5) ribozymes directed against a well-studied target RNA that has therapeutic potential, located in the untranslated 5′ region (U5), to inhibit HIV-1 replication. The two types of ribozymes showed similar antiviral efficacy after being stably transfected into HUT78 cells and subsequently challenged with HIV-1SF2, but the HhU5 ribozyme showed faster cleavage kinetics when tested in a cell-free system. In the second part of this study, we examined whether different ribozymes were able to inhibit the integration of proviral DNA in infected HUT78 cells. We found that cell pools stably expressing HpU5 could limit the appearance of integrated provirus, indicating that they could inhibit the infecting viral RNA before reverse transcription. A preintegration effect was also found for cell pools expressing a ribozyme targeting the nef gene (HhNef) or a ribozyme targeting the LTR (HhLTR). However, no discernible preintegration effects were seen for the HhU5 ribozyme or an active ribozyme directed against an RNA target site in the pol gene (HhPol). Thus, the results suggest that the mode of ribozyme action varied between sites and is not dependent solely on inhibiting the infecting viral RNA. Evidence for a preintegration effect is extremely encouraging and indicates that "resistant" cells have some chance to repopulate the immune system through such a selective advantage. We also studied the ability of the different ribozymes to down regulate viral RNA postintegration.
The Variability of Cardiac Output Estimations Made with the High-Frequency Undamped Balistocardiograph
Authors: ROBERT M. PAINE, NATHAN W. SHOCK
Journal: Circulation (1950)

Recordings of the ballistocardiogram were made on successive days in a group of subjects free from clinical signs of heart disease. The effects of ambulation and meals on the recordings were evaluated. A small but measurable increase in cardiac index following meals was observed. Significant individual differences were found. In order to obtain comparable ballistocardiographic records, it is important for the patient to fast for four to five hours preceding the measurements. However, familiarity with the procedure and prior bed rest are not essential. Only one set of calculations by one observer is required.
Inquiry into the Treatment of Burns and Scalds
Authors: S. Crompton
Journal: BMJ (1848)

importance.A knowledge of the ancient languages will often enable him to trace the vaunted discoveries of modern times in the records of almost forgotten ages, and may save in- vestigation for many a weary hour, or direct his inquiries by many a useful hint into the right channel; while those who reflect how the mind is apt to impress its own preceptions and colouring on all that is foreign to itself, will at once see the advantages of searching out the meaning of an author, whether ancient or modern, in the original words in which such meaning was attempted to be conrveyed.This ,position is well illustrated in the elo- quent Hunterian Oration, lately delivered before the Royal College of Surgeons, by Mr. Grainger-"It is, perhaps," says the author, " one of the highest glories of HUNTER, that in proportion as the philisophic culture of organization has advanced, he who would attempt to record its progress, and especially to trace out the causes that have led to it, must ever and again return to him as to a beacon, which, in place of being obscured bv waning years, has only shone forth in all its fulness and significance in these late and advanced times.* * * * We can at length perceive with the latest aids of sciences, that he neither was, nor could be, understood, in the time in whicl he lived.* * * Amidst the innumerablc additions that have from all quarters flowed in, there are scarcely any which do not fnd their place among the great principles announced by HUNTER; while not a few of the most profound discoveries, equally with the most minute, are but the repetitions of truths which he had long since proclaimed in a language now become clear and expressive.
Carbon Monoxide Pollution Promotes Cardiac Remodeling and Ventricular Arrhythmia in Healthy Rats
Authors: Lucas Andre, Julien Boissière, Cyril Reboul, Romain Perrier, Santiago Zalvidea, Gregory Meyer, Jérôme Thireau, Stéphane Tanguy, Patrice Bideaux, Maurice Hayot, François Boucher, Philippe Obert, Olivier Cazorla, Sylvain Richard
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Epidemiologic studies associate atmospheric carbon monoxide (CO) pollution with adverse cardiovascular outcomes and increased cardiac mortality risk. However, there is a lack of data regarding cellular mechanisms in healthy individuals.To investigate the chronic effects of environmentally relevant CO levels on cardiac function in a well-standardized healthy animal model.Wistar rats were exposed for 4 weeks to filtered air (CO < 1 ppm) or air enriched with CO (30 ppm with five peaks of 100 ppm per 24-h period), consistent with urban pollution. Myocardial function was assessed by echocardiography and analysis of surface ECG and in vitro by measuring the excitation-contraction coupling of single left ventricular cardiomyocytes.Chronic CO pollution promoted left ventricular interstitial and perivascular fibrosis, with no change in cardiomyocyte size, and had weak, yet significant, effects on in vivo cardiac function. However, both contraction and relaxation of single cardiomyocytes were markedly altered. Several changes occurred, including decreased Ca(2+) transient amplitude and Ca(2+) sensitivity of myofilaments and increased diastolic intracellular Ca(2+) subsequent to decreased SERCA-2a expression and impaired Ca(2+) reuptake. CO pollution increased the number of arrhythmic events. Hyperphosphorylation of Ca(2+)-handling and sarcomeric proteins, and reduced responses to beta-adrenergic challenge were obtained, suggestive of moderate CO-induced hyperadrenergic state.Chronic CO exposure promotes a pathological phenotype of cardiomyocytes in the absence of underlying cardiomyopathy. The less severe phenotype in vivo suggests a role for compensatory mechanisms. Arrhythmia propensity may derive from intracellular Ca(2+) overload.
Role of computed tomography and endoscopy in the management of alimentary tract lipomas.
Authors: J Y Kang, C Chan-Wilde, A Wee, R Chew, T K Ti
Journal: Gut (1990)

Four cases of alimentary tract lipomas are described. While conventional radiology is unable to differentiate these tumours from the much commoner carcinomas, computed tomography and endoscopic examination may allow a definitive diagnosis thus sparing the patient major surgery. In selected cases endoscopic polypectomy is feasible and safe.
Abstract 3616: Highly potent antibody-amanitin conjugates cause tumor-selective apoptosis
Authors: Jan Anderl, Christoph Müller, Brigitte Heckl-Östreicher, Roland Wehr
Journal: Cancer Research (2011)

Abstract Alpha-amanitin blocks RNA polymerase II activity and is the most specific and most potent inhibitor of eukaryotic transcription. While widely used as a tool in molecular biology, only a few attempts have been made to employ alpha-amanitin as a therapeutic agent in oncology. The reason for this may be the high liver toxicity caused by the transport of amanitin into hepatocytes by the organic-anion transporter 1B3 (OATP1B3) present on hepatocytes, but not on other cell types. In this study we show that a direct impact on the transcription machinery can provide a novel approach in tumor therapy, provided that the amanitin can be targeted to tumor cells. This was achieved by using tumor-specific antibodies of high affinity armed with amanitin via suitable linker moieties. Using the HER2 specific monoclonal antibody Herceptin (Her) as a carrier, the antibody-drug conjugate (ADC) Her-DSC-30.0134 exhibits antiproliferative activity in HER2-expressing human tumor cell lines like SK-OV-3, SK-BR-3 and NCI-N87 in picomolar concentrations, indicating an up to 100.000-fold higher toxicity of the conjugate over non-conjugated alpha-amanitin. On cells lacking the HER2 receptor, e.g. HEK293 cells, toxicity of Her-DSC-30.0134 was not detected up to micromolar concentrations. This is also observed in HEK293 cells transfected with OATP1B3 (which incorporate amanitin similar as hepatocytes) indicating that amanitin-antibody-conjugates are no longer substrates for OATP1B3. These data suggest that a low hepatotoxicity of amanitin conjugates is expected. Subsequently, antitumoral activity of Her-DSC-30.0134 was evaluated in vivo in a s.c. xenograft mouse model using Herceptin-sensitive SK-OV-3 and Herceptin-resistant JIMT-1 cells. The ADC is well tolerated in nude mice and shows complete tumor remission in 7 out of 7 animals after a single i.v. injection in the SK-OV-3 and JIMT-1 models. By contrast, Herceptin shows only moderate antitumoral activity in the SK-OV-3 and no activity in the resistant JIMT-1 model, even after multiple injections. These data encourages further examination of amanitin-based antibody conjugates as highly potent and selective compounds for the treatment of various maligancies. 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 3616. doi:10.1158/1538-7445.AM2011-3616