tbuckley/cabot-search huggingface dataset:
Tripartite motif-containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear-located RING domain
Authors: Bo Gao, Zhijian Duan, Wei Xu, Sidong Xiong
Journal: Hepatology (2009)

Members of the tripartite motif (TRIM) family are a part of the innate immune system to counter intracellular pathogens. TRIM22 has been reported to possess antiretroviral activity. Here we report that TRIM22 is involved in antiviral immunity against hepatitis B virus (HBV). Our results showed that TRIM22, being a strongly induced gene by interferons in human hepatoma HepG2 cells, could inhibit HBV gene expression and replication in a cell culture system as well as in a mouse model system. Importantly, it was found that TRIM22 could inhibit the activity of HBV core promoter (CP) in a dose-dependent manner. However, TRIM22 lacking the C terminal SPRY domain lost this activity. Further study showed that the SPRY domain deletion mutant was localized exclusively to the cytoplasm of HepG2 cells. In contrast, the wild-type TRIM22 was localized to the nucleus, as expected for a transcriptional suppressor. Interestingly, although RING domain mutants of TRIM22 were localized to the nucleus, they could not inhibit HBV CP activity, indicating that TRIM22-mediated anti-HBV activity was dependent on the nuclear-located RING domain.These findings suggest that TRIM22, which exhibits anti-HBV activity by acting as a transcriptional suppressor, may play an important role in the clearance of HBV.
Fibrosing mediastinitis as a rare mechanism of pulmonary oedema in sarcoidosis
Authors: F. Yangui, J-P. Battesti, D. Valeyre, A. B. Kheder, P-Y. Brillet
Journal: European Respiratory Journal (2010)

Fibrosing mediastinitis as a rare mechanism of pulmonary oedema in sarcoidosisTo the Editors:Pulmonary oedema in sarcoidosis can usually be attributed to congestive heart failure or veno-occlusive disease.Here we report a rare case of pulmonary oedema, which was due to pulmonary vein stenosis secondary to fibrosing mediastinitis.
Sauna builder's asthma caused by obeche (Triplochiton scleroxylon) dust.
Authors: K Reijula, V Kujala, J Latvala
Journal: Thorax (1994)

Two carpenters developed rhinitis, conjunctivitis, bronchial wheezing, and dyspnoea while using obeche (Triplochiton scleroxylon, African maple) at their work while they built saunas. Skin prick tests showed an immediate reaction, specific IgE to obeche was detected in their serum, and bronchial provocation test with obeche gave an immediate reaction with decrease of FEV1 and PEF values. The symptoms disappeared after avoiding the use of obeche. Obeche may cause a health hazard to carpenters who are exposed to this dust and who may develop allergic symptoms after the exposure.
Systemic Treatment with the Antidiabetic Drug Metformin Selectively Impairs p53-Deficient Tumor Cell Growth
Authors: Monica Buzzai, Russell G. Jones, Ravi K. Amaravadi, Julian J. Lum, Ralph J. DeBerardinis, Fangping Zhao, Benoit Viollet, Craig B. Thompson
Journal: Cancer Research (2007)

Abstract The effect of the antidiabetic drug metformin on tumor growth was investigated using the paired isogenic colon cancer cell lines HCT116 p53+/+ and HCT116 p53−/−. Treatment with metformin selectively suppressed the tumor growth of HCT116 p53−/− xenografts. Following treatment with metformin, we detected increased apoptosis in p53−/− tumor sections and an enhanced susceptibility of p53−/− cells to undergo apoptosis in vitro when subject to nutrient deprivation. Metformin is proposed to function in diabetes treatment as an indirect activator of AMP-activated protein kinase (AMPK). Treatment with AICAR, another AMPK activator, also showed a selective ability to inhibit p53−/− tumor growth in vivo. In the presence of either of the two drugs, HCT116 p53+/+ cells, but not HCT116 p53−/− cells, activated autophagy. A similar p53-dependent induction of autophagy was observed when nontransformed mouse embryo fibroblasts were treated. Treatment with either metformin or AICAR also led to enhanced fatty acid β-oxidation in p53+/+ MEFs, but not in p53−/− MEFs. However, the magnitude of induction was significantly lower in metformin-treated cells, as metformin treatment also suppressed mitochondrial electron transport. Metformin-treated cells compensated for this suppression of oxidative phosphorylation by increasing their rate of glycolysis in a p53-dependent manner. Together, these data suggest that metformin treatment forces a metabolic conversion that p53−/− cells are unable to execute. Thus, metformin is selectively toxic to p53-deficient cells and provides a potential mechanism for the reduced incidence of tumors observed in patients being treated with metformin. [Cancer Res 2007;67(14):6745–52]
The Antitumor Immunity of Ipilimumab: (T-cell) Memories to Last a Lifetime?
Authors: Michael A. Postow, Margaret K. Callahan, Jedd D. Wolchok
Journal: Clinical Cancer Research (2012)

Abstract Ipilimumab has shown an overall survival benefit in 2 randomized phase III studies. A minority of patients achieve long-term disease control, highlighting the potential of this immunotherapeutic approach. In ongoing efforts, investigators are continuing to characterize these patients' unique clinical courses and correlate their responses with underlying mechanisms of antitumor immunity. Clin Cancer Res; 18(7); 1821–3. ©2012 AACR.
Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure
Authors: V Gülberg, S Møller, Jens Henrik Sahl Henriksen, A L Gerbes
Journal: Gut (2000)

<h3>BACKGROUND/AIMS</h3> C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is considered to be involved in the regulation of vascular tone. Furthermore, the recent demonstration of CNP in human kidney and urine may indicate a role for CNP in fluid and electrolyte homeostasis. Therefore, the aim of the present study was to investigate the possible role of CNP in renal function disturbances in patients with cirrhosis of the liver. <h3>METHODS</h3> Peripheral venous and urinary concentrations of CNP were determined in samples from 11 healthy controls, 20 cirrhotic patients with normal renal function (creatinine clearance 117 (8) ml/min), and 20 cirrhotic patients with impaired renal function (creatinine clearance 35 (4) ml/min). In a second protocol, arterial and renal venous plasma concentrations of CNP were determined in 37 patients with cirrhosis of the liver to estimate renal extraction ratios of CNP. A sensitive and specific radioimmunoassay was applied after solid phase extraction of samples. <h3>RESULTS</h3> Plasma CNP was lower in cirrhotic patients with normal and impaired renal function than in controls (3.0 (0.4) and 2.7 (0.2)<i>v</i> 4.2 (0.4) pg/ml, respectively; p&lt; 0.05; mean (SEM)). In contrast, urinary CNP was higher in patients with impaired renal function compared with those with normal renal function and healthy controls (47.2 (7.4) <i>v</i> 20.8 (1.9) and 17.0 (3.0) ng CNP/g creatinine, respectively; p&lt;0.05). Urinary CNP was found to be inversely related to urinary sodium excretion in cirrhotic patients (<i>r</i>=−0.56; p&lt;0.01). No differences were observed between arterial and renal venous concentrations of CNP in cirrhosis (2.4 (0.2)<i>v</i> 2.4 (0.2) pg/ml). In cirrhotic patients with hepatorenal syndrome or refractory ascites (n=5), urinary CNP decreased from 132 (59) to 38 (7) ng/g creatinine (p&lt;0.05) one week after either ornipressin infusion or insertion of a transjugular intrahepatic portosystemic shunt together with an increase in urinary sodium excretion from 27 (17) to 90 (34) mmol/24 hours. <h3>CONCLUSIONS</h3> Increased urinary CNP in cirrhotic patients in the absence of renal arteriovenous concentration gradients suggests enhanced renal CNP production in cirrhosis. Furthermore, an inverse relation between urinary CNP and urinary sodium excretion suggests a role for this peptide in renal sodium handling in patients with cirrhosis.
Perforating and non-perforating indications for repeated operations in Crohn's disease: evidence for two clinical forms.
Authors: A J Greenstein, P Lachman, D B Sachar, J Springhorn, T Heimann, H D Janowitz, A H Aufses
Journal: Gut (1988)

The surgical indications in 770 patients with Crohn's disease undergoing intestinal resection at The Mount Sinai Hospital from 1960-83 have been reviewed. Surgical indications were divided into two principal categories: 375 cases with perforating indications and 395 cases non-perforating. Among 292 patients who underwent second operations for recurrent Crohn's disease, the indications for second operation were closely dependent on the indication for primary resection. Second operations were undertaken for perforating indications much more often among cases where the initial indication had been perforating, than among those whose initial indications had been non-perforating (73% v 29%, p less than 0.00001). This trend to similarities in the indications which bring patients to surgery was maintained within each anatomical category of Crohn's disease and even between second and third operations (p less than 0.001). Operations for perforating indications were followed by reoperation approximately twice as fast as operations for non-perforating indications, whether going from first to second operation (perforating 4.7 v non-perforating 8.8 years, p less than 0.001), or from second to third (perforating 2.3 v non-perforating 5.2 years, p less than 0.005). Crohn's disease thus seems to occur in two different clinical patterns, independent of anatomic distribution. These are a relatively aggressive perforating type and a more indolent non-perforating type, which tend to retain their identities between repeated operations and to influence the speed with which reoperation occurs.
Education as Part of the Health Care Solution
Authors: Edward H. O'Neil
Journal: JAMA (1992)

THESE are extremely turbulent times for health care, the health professions, and the educational institutions that prepare professionals for service to the public. Most discussion regarding reform tends to focus on the health care provision and financing systems, ignoring two key components of change: health care manpower and the education of providers. The public resources that have built educational institutions and the health care system over the past four decades are now severely limited. How will medical schools and teaching hospitals begin the task of developing new educational responses to the nation's health care needs? What will drive the change needed in the schools and hospitals to ensure that our future physicians and care providers can support and practice in a changed system? Over the past 8 years, the Pew Charitable Trusts have focused on achieving within schools the structural changes that empower them to respond more effectively to the
Embryonic exposure to excess thyroid hormone causes thyrotrope cell death
Authors: Ksenia N. Tonyushkina, Meng-Chieh Shen, Theresa Ortiz-Toro, Rolf O. Karlstrom
Journal: Journal of Clinical Investigation (2013)

Central congenital hypothyroidism (CCH) is more prevalent in children born to women with hyperthyroidism during pregnancy, suggesting a role for thyroid hormone (TH) in the development of central thyroid regulation. Using the zebrafish embryo as a model for thyroid axis development, we have characterized the ontogeny of negative feedback regulation of thyrotrope function and examined the effect of excess TH on thyrotrope development. We found that thyroid-stimulating hormone β subunit (tshb) and type 2 deiodinase (dio2) are coexpressed in zebrafish thyrotropes by 48 hours after fertilization and that TH-driven negative feedback regulation of tshb transcription appears in the thyroid axis by 96 hours after fertilization. Negative feedback regulation correlated with increased systemic TH levels from the developing thyroid follicles. We used a transgenic zebrafish that expresses GFP under the control of the tshb promoter to follow thyrotrope fates in vivo. Time-lapse imaging revealed that early exposure to elevated TH leads to thyrotrope cell death. Thyrotrope numbers slowly recovered following the removal of excess TH. These data demonstrate that transient TH exposure profoundly impacts the thyrotrope population during a critical period of pituitary development and may have long-term implications for the functional reserve of thyroid-stimulating hormone (TSH) production and the TSH set point later in life.
Purification of γ-Glutamyltransferases from Rat Hepatomas and Hyperplastic Hepatic Nodules, and Comparison with the Enzyme from Rat Kidney
Authors: Shigeki Tsuchida, Keiji Hoshino, Tsuyoshi Sato, Nobuyuki Ito, Kiyomi Sato
Journal: Cancer Research (1979)

y-Glutamyltransferases that increase during rat hepatocarcinogenesis were compared Âimmunochemically and electrophoretically with the enzyme from the adult rat kidney. The activity of this enzyme did not differ among hyperplastic hepatic nodules and histologically different primary hepatomas induced by A/-2-fluorenylacetamide, dimethylnitrosamine and 3'-methyl4-dimethylaminoazobenzene; thus this enzyme was confirmed to be a useful marker for preneoplastic hepatocytes. The enzymes purified from the Yoshida ascites hepatomas and primary hepatomas as well as from hyperplastic nodules were immunologically identical with the kidney enzyme in the activity inhibition and in the double diffusion tests using antibodies against the enzymes from the Yoshida AH 13 and from the kidney. They also consisted of heavy and light subunits, almost identical with those of the kidney enzyme on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, as well as immu nologically. However, on isoelectric focusing in polyacrylamide gel the purified kidney enzyme showed multiple molecular forms, while the enzymes purified from hyperplastic nodules and hepatomas showed a single form, which was more acidic than any form of the kidney enzyme, apparently owing to a higher content of sialic acid. These results indicate that yglutamyltransferases that increase in hepatocarcinogenesis are identical with the kidney enzyme in the protein portion, but differ in the sugar portion. This appears to be an oncofetal alteration of this enzyme.
CORTICAL NEURAL PROSTHETICS
Authors: Andrew B. Schwartz
Journal: Annual Review of Neuroscience (2004)

Control of prostheses using cortical signals is based on three elements: chronic microelectrode arrays, extraction algorithms, and prosthetic effectors. Arrays of microelectrodes are permanently implanted in cerebral cortex. These arrays must record populations of single- and multiunit activity indefinitely. Information containing position and velocity correlates of animate movement needs to be extracted continuously in real time from the recorded activity. Prosthetic arms, the current effectors used in this work, need to have the agility and configuration of natural arms. Demonstrations using closed-loop control show that subjects change their neural activity to improve performance with these devices. Adaptive-learning algorithms that capitalize on these improvements show that this technology has the capability of restoring much of the arm movement lost with immobilizing deficits.
Little Fox Goes to the End of the World
Authors: K. M. Beckmann
Journal: BMJ (2012)

As medical doctors or parents, our agenda is to protect children from harm and to prepare them for the future. We wish for the best physical and mental health and we do our best to encourage preparedness. These earliest years are essential in equipping the next generation with the skills they need to face the world of the 21st century. 

Sadly, it is unlikely that a child will always be protected from trauma. Not every child will be injured, whether physically or mentally, but many unfortunately will. And not all children who have experienced adverse events will come to …
The fasting B6 vitamer profile and response to a pyridoxine load in normal and cirrhotic subjects
Authors: Michael J. Henderson, Mark A. Codner, Bettye Hollins, Michael H. Kutner, Alfred H. Merrill
Journal: Hepatology (1986)

This study established the fasting plasma and urine profiles of vitamin B 6 in cirrhotics and assessed the response to an oral dose of pyridoxine. High-performance liquid chromatography was used to measure all vitameric coenzymatic and degradatory forms. In 31 patients with cirrhosis and 15 healthy controls, fasting plasma and 24-hr urine collection showed: plasma pyridoxal-5′-phosphate, the biologically active form, was significantly (p&lt;0.001) reduced in cirrhotics (mean ± S.D.: 5.7 ± 3.2 ng per ml) compared to normals (14.2 ± 7.5 ng per ml); plasma pyridoxal was detected in more cirrhotics (48%) than normals (28%); pyridoxic acid, the end catabolite, was significantly (p&lt;0.05) lower in plasma of cirrhotics compared to normals, but 24-hr urine excretion was not different. Administration of 25 mg of pyridoxine to 7 cirrhotics and 5 normals showed the following plasma changes: (i) pyridoxine rapidly peaked at 30 min and was totally cleared from plasma by 3 hr; (ii) plasma pyridoxal and pyridoxic acid increased in parallel up to 40-fold over baseline by 1 to 2 hr and rapidly fell toward baseline by 8 hr, and (iii) plasma pyridoxal-5′-phosphate, in contrast, increased significantly (p&lt;0.05) from baseline by 60 min and was maintained above normal for 24 hr. The area under the plasma concentration vs. time curve (AUC) for pyridoxal-5′-phosphate was significantly (p&lt;0.05) less for the cirrhotics than normals and showed a significant negative correlation to hepatocyte function and blood flow. This suggests that it is most difficult to replete plasma pyridoxal-5′-phosphate in those cirrhotics with best preservation of liver function and flow. In contrast, the plasma pyridoxal AUC is significantly (p&lt;0.025) greater in the cirrhotics after the pyridoxine load. Plasma pyridoxic acid AUC and urine pyridoxic acid excretion (27% of load per 24 hr) are not significantly different for the two groups. The data are consistent with normal pyridoxal-5′-phosphate synthesis since plasma pyridoxal-5′-phosphate levels are maintained within the normal range by a single 25 mg oral dose of pyridoxine. However, the smaller AUC for pyridoxal-5′-phosphate in cirrhotics compared to normals, combined with the increased pyridoxal AUC, shows increased bydrolysis to pyridoxal. This is not excreted as pyridoxic acid and suggests that pyridoxal may be entering intracellular sites.
Total Knee Arthroplasty Volume, Utilization, and Outcomes Among Medicare Beneficiaries, 1991-2010
Authors: Peter Cram, Xin Lu, Stephen L. Kates, Jasvinder A. Singh, Yue Li, Brian R. Wolf
Journal: JAMA (2012)

<h3>Context</h3>Total knee arthroplasty (TKA) is one of the most common and costly surgical procedures performed in the United States.<h3>Objective</h3>To examine longitudinal trends in volume, utilization, and outcomes for primary and revision TKA between 1991 and 2010 in the US Medicare population.<h3>Design, Setting, and Participants</h3>Observational cohort of 3 271 851 patients (aged ≥65 years) who underwent primary TKA and 318 563 who underwent revision TKA identified in Medicare Part A data files.<h3>Main Outcome Measures</h3>We examined changes in primary and revision TKA volume, per capita utilization, hospital length of stay (LOS), readmission rates, and adverse outcomes.<h3>Results</h3>Between 1991 and 2010 annual primary TKA volume increased 161.5% from 93 230 to 243 802 while per capita utilization increased 99.2% (from 31.2 procedures per 10 000 Medicare enrollees in 1991 to 62.1 procedures per 10 000 in 2010). Revision TKA volume increased 105.9% from 9650 to 19 871 while per capita utilization increased 59.4% (from 3.2 procedures per 10 000 Medicare enrollees in 1991 to 5.1 procedures per 10 000 in 2010). For primary TKA, LOS decreased from 7.9 days (95% CI, 7.8-7.9) in 1991-1994 to 3.5 days (95% CI, 3.5-3.5) in 2007-2010 (P &lt; .001). For primary TKA, rates of adverse outcomes resulting in readmission remained stable between 1991-2010, but rates of all-cause 30-day readmission increased from 4.2% (95% CI, 4.1%-4.2%) to 5.0% (95% CI, 4.9%-5.0%) (P &lt; .001). For revision TKA, the decrease in hospital LOS was accompanied by an increase in all-cause 30-day readmission from 6.1% (95% CI, 5.9%-6.4%) to 8.9% (95% CI, 8.7%-9.2%) (P &lt; .001) and an increase in readmission for wound infection from 1.4% (95% CI, 1.3%-1.5%) to 3.0% (95% CI, 2.9%-3.1%) (P &lt; .001).<h3>Conclusions</h3>Increases in TKA volume have been driven by both increases in the number of Medicare enrollees and in per capita utilization. We also observed decreases in hospital LOS that were accompanied by increases in hospital readmission rates.
Simultaneous passive and active immunization against hepatitis B: Noninterference of hepatitis B immune globulin with the anti-HBs response to reduced doses of heat-inactivated hepatitis B vaccine
Authors: P. Nico Lelie, Henk W. Reesink, Rob Grijm, Sonja Th. de Jong-Van Manen, Eveline E. Reerink-Brongers
Journal: Hepatology (1986)

The effect of simultaneous administration of hepatitis B immune globulin on the antibody response to a low dose of heat-inactivated hepatitis B vaccine was investigated in 175 health care workers. Subjects were divided into four groups: Groups I and II received 3 monthly injections of a reduced dose (0.6 μg) of a heat-inactivated hepatitis B vaccine (the usual dose being 3 μg) along with 500 IU of hepatitis B immune globulin simultaneously with the first injection of vaccine; Groups III and IV received the vaccine only. In addition, Groups I and III received a final booster injection with 0.6 μg of the vaccine 8 months after the initial injection. Anti-HBs passively acquired from hepatitis B immune globulin did not interfere with the development of an active antibody response to the vaccine: the anti-HBs conversion rates were similar in persons treated with the combined regimen (89%) as in those who received the vaccine only (91%). At 3 and 5 months after the first injection, however, anti-HBs titers in the recipients of vaccine alone were slightly but statistically significantly higher than those of persons who received both hepatitis B immune globulin and vaccine; but at 8 months, this difference was no longer statistically significant. After a booster inoculation at 8 months, the geometric mean titer of anti-HBs increased 7- to 8-fold in antibody-positive vaccinees, regardless of whether hepatitis B immune globulin had been given earlier. Moreover, 6 of 13 nonresponders to the initial three vaccine injections developed anti-HBs after the booster inoculation. Thus, passively acquired anti-HBs does not interfere with an active antibody response to hepatitis B vaccine even when a low dose of vaccine is used. Furthermore, a final booster vaccine inoculation, several months after the initial series of injections, is important in providing high response rates and sustained high titers of anti-HBs.