Miracle-dz/UniFAR-FTUs huggingface dataset:
Hyperinsulinemia—How Innocent a Bystander?

Hyperinsulinemia is very much in the spotlight. Debate rages as to its significance and role in the etiology not only of NIDDM, but also other morphological and metabolic risk factors for atherosclerotic cardiovascular disease, including upper-body obesity, dyslipidemia, hypertension, and hyperuricemia. Epidemiological data support a key role for hyperinsulinemia in these disorders but it is far from conclusive except for the fact that hyperinsulinemia and insulin resistance may be present many years before the onset of impaired glucose tolerance and NIDDM, and clearly play a role in their etiology. The thrifty genotype hypothesis provides a plausible basis for a better understanding of how hyperinsulinemia and insulin resistance could lead to glucose intolerance and atherosclerotic cardiovascular disease, but the detailed biochemical mechanisms remain elusive. A role for increased sympathetic nervous system activity, resulting from hypothalamic stimulation as a primary event causing hyperinsulinemia, cannot be excluded as a cause of hyperinsulinemia. The current focus on hyperinsulinemia also has resulted in closer examination of the therapy of diabetes and hypertension, emphasizing the need to avoid hyperinsulinemia in both IDDM and NIDDM individuals because of the putative risk of atherosclerotic cardiovascular disease and hypertension. There is still a paucity of epidemiological data to support a role for hyperinsulinemia in the etiology of hypertension. However, clinical practice already is being influenced by the fact that ACE inhibitors have been shown to reduce insulin resistance in clinical research studies. The research reviewed here, particularly that relating to hyperinsulinemia, insulin resistance, and cardiovascular disease risk factors, has opened new vistas for the treatment and prevention of NIDDM and atherosclerotic cardiovascular disease. Appropriate exercise clearly is associated with improved insulin sensitivity, modification of CVD risk factors, and lower prevalence of NIDDM. Upper-body obesity, the latest culprit in the field, can also be reduced by exercise. Hyperinsulinemia and insulin resistance can be detected in children, adolescents, and young adults. NIDDM can be prevented, but clearly, intervention needs to commence in childhood, and intensive risk factor intervention in subjects with NIDDM can reduce the risk of atherosclerotic cardiovascular disease. It seems paradoxical that prevention of NIDDM and atherosclerotic cardiovascular disease are now possible even though the biochemical and molecular basis of these disorders is not fully understood.
HPV‐18 E6*I modulates HPV‐18 full‐length E6 functions in a cell cycle dependent manner

The E6 ORFs of the high‐risk Human Papillomavirus (HPV) Types 16 and 18 have been shown to encode (besides the full‐length product) several truncated forms, termed E6*. We have reported previously that the HPV‐18 E6*I protein interacts with the full‐length E6 protein as well as with the ubiquitin ligase E6‐AP and, as a result of this, E6* can inhibit E6‐mediated degradation of p53. Moreover, ectopic expression of the HPV‐18 E6*I protein has an antiproliferative effect in cervical cancer‐derived cell lines. These results led us to investigate further the modulatory functions of E6*I on E6. Using epitope tagged versions of the 2 proteins we have analyzed the sub‐cellular distribution of the full‐length HPV18 E6 and HPV18 E6*I, as well as their respective cellular abundance during the cell cycle, and show specific upregulation of E6*I during G2/M. We also investigated the effect of E6*I overexpression in cell lines derived from cervical tumors, with respect to the expression levels of E6 target proteins, such as p53, hDlg and Scribble and find a corresponding increase in p53 expression also during G2/M. In addition we show that the overexpression of E6*I reduces the amount of E6 in the insoluble nuclear and membrane fractions of the cell. E6 levels can, however, be restored by the addition of a specific proteasome inhibitor, suggesting that the interaction between E6 and E6*I leads to the destabilization of a subset of the E6 protein. These results suggest that the E6*I protein can function as a fine regulator of the full‐length E6 protein by direct interaction that leads both to changes in its cellular abundance as well as its distribution during particular phases of the cell cycle. © 2004 Wiley‐Liss, Inc.
Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancer

Aim: New biomarkers other than carbohydrate antigen (CA) 125 are needed for the detection of ovarian cancer. Osteopontin (OPN) is one of the candidates identified by high‐throughput complementary DNA microarray techniques. We evaluated the preoperative plasma OPN level as a diagnostic biomarker for ovarian cancer in comparison with CA125.
Lung CT: Part 2, The interstitial pneumonias--clinical, histologic, and CT manifestations.

OBJECTIVE The interstitial pneumonias are a group of heterogeneous nonneoplastic lung diseases that may be idiopathic or associated with an underlying abnormality. Although they share some features in common, they also exhibit diverse pulmonary manifestations. Imaging plays an essential role in characterizing this group of disorders and can often suggest the diagnosis, though the final interpretation requires a coordinated effort involving the radiologist, pathologist, and clinician. The purpose of this article is to review the imaging features of the interstitial pneumonias according to their histologic patterns and to provide a brief overview of their clinical presentations. CONCLUSION This article reviews the interstitial pneumonias according to their histologic subtypes, including both idiopathic and secondary forms. On completion, the reader should have an improved understanding of the classification of the interstitial pneumonias, associated causes, characteristic imaging features, histologic descriptions, clinical manifestations, and prognoses.
Modeling of VSC-Based HVDC Systems for a Newton-Raphson OPF Algorithm

The paper presents the model of a voltage source converter -high voltage direct current (VSC-HVDC) suitable for optimal power flow (OPF) solutions using Newton's algorithm. The VSC-HVDC's ability to provide independent control of the converters ac voltage magnitudes and phase angles relative to the system voltage, which allows the use of separate active and reactive power control loops for system regulation, is well represented by the model. In this new development in Newton OPF, the VSC-HVDC system equations are incorporated directly into the matrix W for a unified optimal solution in a single frame-of-reference. The multipliers method is used to handle all inequality constraints of variables, leading to highly efficient OPF solutions of constrained power networks. The solution approach does not require structural changes in the linearised system of equations during the iterative process using Newton's method. The effectiveness of the VSC-HVDC model and its proposed implementation in Newton OPF is demonstrated by means of two sample systems.
Treatment of chronic gout in patients with renal function impairment: an open, randomized, actively controlled study.

Treatment of gout and hyperuricemia can be difficult in patients with chronic renal failure. At present, there is no study available comparing the efficacy of the most widely used agent, allopurinol, and the uricosuric benzbromarone for the control of hyperuricemia in patients with renal insufficiency. We describe an open, randomized, actively controlled, comparative trial in patients with clearance of creatinine from 20 to 80 mL/ min/1.73 m(2). Patients were randomized to take benzbromarone (100-200 mg/day) or allopurinol (100-300 mg/day). Outcome variables were the following: reduction of serum urate (Sur), Sur & tl; 6 mg/dL (357 micromol/L), reduction of gouty bouts and reduction of tophi. During 9-24 months of follow-up 36 patients were studied.The reduction of Sur was higher with benzbromarone, and only 1 of 17 patients taking benzbromarone did not achieve Sur < 6 mg/dL versus 7 of 19 taking allopurinol. Patients who did not reach optimal Sur levels with allopurinol were more frequently taking diuretics and showed lower fractional excretion of urate and higher initial Sur levels than patients with proper control of Sur. Seven patients with suboptimal control of serum urate were changed to benzbromarone 100 mg/day, which showed efficacy similar in those who were initially randomized to benzbromarone. A reduction of gouty bouts and size of tophi was observed after proper control of Sur. Allopurinol is effective in controlling hyperuricemia, but patients with higher initial Sur levels or taking concomitant diuretic therapy are less prone to reach therapeutic goals.Benzbromarone is useful for the control of hyperuricemia in patients with renal insufficiency even with concomitant diuretic administration; patients benefited include those who previously had no improvement by taking allopurinol.
Neuromuscular diseases as models of cardiovascular regulation during exercise.

This article reviews the research performed to date on the cardiovascular responses to exercise in patients with neuromuscular diseases and lesions affecting the transmission of afferent impulses from skeletal muscle. These studies have provided important information about the roles of central command and reflexes from skeletal muscle afferents in circulatory control. Few animal models of neuromuscular diseases are available. Studies of patients with specific defects in skeletal muscle energy metabolism are particularly valuable because the local metabolic state participates in both systemic and local cardiovascular regulation. In patients with certain muscle metabolic defects (e.g., McArdle's disease, carnitine deficiency) cardiac output is normal at rest but increases excessively in relation to oxygen uptake during exercise. The excessive increase in cardiac output during exercise can be totally or partially normalized by increasing the availability of substrate to exercising muscle. These studies provide unique insights into the specific metabolic factors which are involved in cardiovascular regulation.
Effective vaccination of mice against Mycobacterium tuberculosis infection with a soluble mixture of secreted mycobacterial proteins

An experimental vaccine that was based on secreted proteins of Mycobacterium tuberculosis was investigated in a mouse model of tuberculosis. I used a short-term culture filtrate (ST-CF) containing proteins secreted from actively replicating bacteria grown under defined culture conditions. The immunogenicity of the ST-CF was investigated in combination with different adjuvants, and peak proliferative responses were observed when ST-CF was administered with the surface-active agent dimethyldioctadecylammonium chloride. The immunity induced by this vaccine was dose dependent, and, in the optimal concentration, the vaccine induced a potent T-helper 1 response which efficiently protected the animals against a subsequent challenge with virulent M. tuberculosis. Antigenic targets for the T cells generated were mapped by employing narrow-molecular-weight fractions of ST-CF. The experimental vaccine primed a broadly defined T-cell repertoire directed to multiple secreted antigens present in ST-CF. A vaccination with viable Mycobacterium bovis bacillus Calmette-Guérin (BCG), in contrast, induced a restricted T-cell reactivity directed to two secreted protein fractions with molecular masses of 5 to 12 and 25 to 35 kDa. The protective efficacy of the ST-CF vaccine was compared with that of a BCG standard vaccine, and both induced a highly significant protection of equal magnitude. The vaccination with ST-CF gave rise to a population of long-lived CD4 cells which could be isolated 22 weeks after the vaccination and could adoptively transfer acquired resistance to T-cell-deficient recipients. My results confirm the hypothesis that M. tuberculosis cells release protective antigens during growth. The high efficacy of a subunit vaccine observed in the present study is discussed as a possible alternative to a live recombinant vaccine carrier.
Plasma levels of false neurotransmitters across the brain in portal‐systemic encephalopathy

Abstract. Arterial and internal jugular venous levels of false neurotransmitters (FNTs: octopamine, OCT, and phenylethanolamine, PEA), aromatic and branched‐chain amino acids, glutamine, ammonia, and pH were measured in patients with portal‐systemic encephalopathy (PSE) and in appropriate controls to define the role of these parameters in the pathogenesis of hepatic coma. The typical plasma patterns reported in the literature were observed: hyperammonaemia (59 ± 8 μmol/l v. controls 30 ± 4, P < 0.005), elevated OCT (19 ± 3 nmol/l v. 6 ± 1, P < 0.001) and PEA (64 ± 8 nmol/l v. 27 ± 3, P < 0.001), high ratio of aromatic to branched‐chain amino acids (0.92 ± 0.12 v. 0.32 ± 0.04, P < 0.005), and variable glutamine levels (216–734 μmol/l). No consistent net flux into or out of the brain could be demonstrated for any of these substances. The degree of encephalopathy correlated with the level of respiratory alkalosis (r= 0.325, P < 0.05) which, in turn, correlated with the degree of elevation of plasma OCT (r= 0.439, P < 0.05) and PEA (r= 0.489, P < 0.05) as well as with the excess of glutamine efflux from the brain (r= 0.927, P < 0.05).
Fatty acid esters of 3-chloropropane-1,2-diol in edible oils

A series of 25 virgin and refined edible oils, obtained from retailers, was analyzed for levels of free 3-chloropropane-1,2-diol (3-MCPD) and 3-MCPD released from esters with higher fatty acids (bound 3-MCPD). Oils containing free 3-MCPD ranging from <3 µg kg−1 (LOD) to 24 µg kg−1. Surprisingly, bound 3-MCPD levels were much higher and varied between <100 (LOD) and 2462 µg kg−1. On average, virgin oils had relatively low levels of bound 3-MCPD, ranging from <100 (LOD) to <300 µg kg−1 (LOQ). Higher levels of bound 3-MCPD were found in oils from roasted oilseeds (337 µg kg−1) and in the majority of refined oils (<300–2462 µg kg−1), including refined olive oils. In general, it appears that the formation of bound 3-MCPD in oils is linked to preliminary heat treatment of oilseeds and to the process of oil refining. Analysis of unrefined, de-gummed, bleached, and deodorized rapeseed oil showed that the level of bound MCPD decreased during the refining process. However, additional heating of seed oils for 30 min at temperatures ranging from 100 to 280°C, and heating at 230°C (260°C) for up to 8 h, led to an increase in bound 3-MCPD levels. On the other hand, heating of olive oil resulted in a decrease in bound 3-MCPD levels. For comparison, fat isolated from salami was analyzed for intact fatty acid esters of 3-MCPD. This fat contained bound 3-MCPD at a level of 1670 µg kg−1 and the fatty acid esters of 3-MCPD mainly consisted of 3-MCPD diesters; monoesters of 3-MCPD were present in smaller amounts. The major types of 3-MCPD diesters (about 85%) were mixed diesters of palmitic acid with C18 fatty acids (stearic, oleic, linoleic acids). These diesters were followed by 3-MCPD distearate (11%) and 3-MCPD dipalmitate (4%). Generally, very little 3-MCPD existed as the free compound (31 µg kg−1).
Chinese herbal medicine Tianqi reduces progression from impaired glucose tolerance to diabetes: a double-blind, randomized, placebo-controlled, multicenter trial.

CONTEXT Living in a prediabetes state significantly increases a patient's risk for both diabetes and cardiovascular disease. Tianqi capsule, containing 10 Chinese herbal medicines, is used in China for the treatment of type 2 diabetes mellitus (T2DM). OBJECTIVE The purpose of this study was to assess whether Tianqi prevented T2DM in subjects with impaired glucose tolerance (IGT) over the course of a 12-month treatment. METHODS Individuals with IGT were randomly allocated in a double-blind manner to receive Tianqi (n = 210) or a placebo (n = 210) for 12 months. Oral glucose tolerance tests were conducted every 3 months to assess the development of diabetes or restoration to normal glucose tolerance. All subjects received the same lifestyle education. The primary endpoint was the conversion of IGT to T2DM. Body weight and body mass index were observed. Adverse effects were monitored. RESULTS Of the 420 enrolled subjects with IGT, 389 completed the trial (198 in the Tianqi group and 191 in the placebo group). At the end of the 12-month trial, 36 subjects in the Tianqi group (18.18%) and 56 in the placebo group (29.32%) had developed diabetes (P = .01). There was a significant difference in the number of subjects who had normal glucose tolerance at the end of the study between the Tianqi and placebo groups (n = 125, 63.13%, and n = 89, 46.60%, respectively; P = .001). Cox's proportional hazards model analysis showed that Tianqi reduced the risk of diabetes by 32.1% compared with the placebo. No severe adverse events occurred in the trial. There were no statistical differences in body weight and body mass index changes between the Tianqi group and the placebo group during the 12-month trial. CONCLUSIONS Treatment with a Tianqi capsule for 12 months significantly decreased the incidence of T2DM in subjects with IGT, and this herbal drug was safe to use.
Toxicity and efficacy of escalating dosages of recombinant human interleukin-6 after chemotherapy in patients with breast cancer or non-small-cell lung cancer.

PURPOSE To evaluate the safety, tolerability, and efficacy of varying doses of recombinant human interleukin-6 (rhIL-6) after chemotherapy. PATIENTS AND METHODS In this phase I/II study, 19 breast (stage III to IV) or non-small-cell lung cancer (NSCLC) patients received mitoxantrone (10 mg/m2) and thiotepa (40 mg/m2) every 3 weeks, followed by rhIL-6 subcutaneously (days 5 to 15) at six dose levels: 0.5, 1.0, 2.5, 5.0, 10.0, and 20.0 micrograms/kg/d body weight/d (micrograms/kg/d). rhIL-6 was increased to the next level in the individual patient in case of incomplete bone marrow recovery (leukocyte count < 3 x 10(9)/L and/or platelet count < 100 x 10(9)/L at day 22) and/or platelet nadir less than 25 x 10(9)/L in two consecutive cycles. RESULTS Flu-like symptoms were observed in most of the patients. Nausea and vomiting were reported in seven of 48 and 19 of 48 cycles, respectively. Dose-limiting toxicity at 20.0 micrograms/kg/d of rhIL-6 consisted of World Health Organization (WHO) grade 3 to 4 flu-like symptoms, nausea, and vomiting. Platelet recovery was faster in cycle 1 at 10.0 and 20.0 micrograms/kg/d of rhIL-6 than at lower dose levels (P < .05); thrombocytopenia grade 4 was observed at most levels. However, only two patients needed platelet transfusions (1.0 and 2.5 micrograms/kg/d rhIL-6). rhIL-6 effects on leukocytes were not dose-related, with a trend for the neutrophil nadir to increase with rhIL-6 up to 10 micrograms/kg/d. rhIL-6 dose escalation did not affect hematologic parameters and chemotherapy cycle duration. Hemoglobin (P < .001) and cholesterol (P < .05) levels decreased, while acute-phase proteins increased. CONCLUSION rhIL-6 following chemotherapy is tolerable up to 10 micrograms/kg/d; flu-like symptoms and nausea were dose-limiting at 20 micrograms/kg/d. Platelet nadir did not differ for the various rhIL-6 doses. However, a faster platelet recovery was observed at 10.0 and 20.0 micrograms/kg/d of rhIL-6.
Effect of ischemia‐reperfusion on the post‐rest inotropy of isolated perfused rat heart

This paper aims to study of the effects of ischemia‐reperfusion on the post‐rest inotropy and to characterize post‐rest B1:B2 ratio as an index of intracellular Ca2+ overload. When the rest interval between the cardiac beats is increased, the magnitude of the post‐rest beats is increased. First beat (B1) is maximally potentiated with exponental decline of the second (B2) and subsequent beats, thereby establishing a normal B1:B2 ratio of post‐ rest inotropy of the cardiac muscle. The rest potentiation of B1 and subsequent decay in the magnitude B2 is thought to develop from the time‐dependent changes in the Ca2+‐uptake and release from the sarcoplasmic reticulum (SR). Ca2+‐kinetics of SR can be modulated by a variety of interventions which produce Ca2+ loading of the SR.
Down‐regulation of cAMP‐dependent protein kinase by over‐activated calpain in Alzheimer disease brain

Impaired cognition and memory may be associated with down‐regulation of cAMP‐response element‐binding protein (CREB) in the brain in patients with Alzheimer disease, but the molecular mechanism leading to the down‐regulation is not understood. In this study, we found a selective reduction in the levels of the regulatory subunits (RIIα and RIIβ) and the catalytic subunit (Cβ) as well as the enzymatic activity of cAMP‐dependent protein kinase (PKA), which is the major positive regulator of CREB. We also observed that PKA subunits were proteolyzed by calpain and the levels of PKA subunits correlated negatively with calpain activation in the human brain. These findings led us to propose that in the brain in patients with Alzheimer disease, over‐activation of calpain because of calcium dysregulation causes increased degradation and thus decreased activity of PKA, which, in turn, contributes to down‐regulation of CREB and impaired cognition and memory.
PX‐RICS, a novel splicing variant of RICS, is a main isoform expressed during neural development

In our previous study, we identified RICS, a novel β‐catenin‐interacting protein with the GAP activity toward Cdc42 and Rac1, and found that RICS plays an important role in the regulation of neural functions, including postsynaptic NMDA signaling and neurite outgrowth. Here we report the characterization of an N‐terminal splicing variant of RICS, termed PX‐RICS, which has additional phox homology (PX) and src homology 3 (SH3) domains in its N‐terminal region. The PX domain of PX‐RICS interacted specifically with phosphatidylinositol 3‐phosphate [PtdIns(3)P], PtdIns(4)P and PtdIns(5)P. Consistent with this binding affinity, PX‐RICS was found to be localized at the endoplasmic reticulum (ER), Golgi and endosomes. We also found that wild‐type PX‐RICS possessed much lower GAP activity than RICS, whereas a mutant form of PX‐RICS whose PX domain lacks the binding ability to phosphoinositides (PIs) exhibited the GAP activity comparable to that of RICS. However, PX‐RICS and RICS exhibited similar inhibitory effects on neurite elongation of Neuro‐2a cells. Furthermore, we demonstrate that PX‐RICS is a main isoform expressed during neural development. Our results suggest that PX‐RICS is involved in early brain development including extension of axons and dendrites, and postnatal remodeling and fine‐tuning of neural circuits.
Annotation contextuelle automatique avec PhotoMap

We present a mobile and context-aware system, called PhotoMap that provides semi-automatic annotation about the spatial, temporal and social contexts of a photo. (i.e., where, when, who and what was nearby). The PhotoMap application captures the photo shot context when a user takes a picture with her camera phone. The mobile client gets the geographic position of the device, date and time information, bluetooth addresses of the nearby devices. PhotoMap explores these gathered metadata to infer high level contextual information such as, nearby user's friends, weather conditions, device address, and nearby important objects. PhotoMap uses these metadata for organizing, sharing and retrieving the photo files.
Mitochondrial genome of the Emberiza aureola (Emberizidae: Emberiza)

Abstract The Emberiza aureola (yellow-breasted bunting), Vulnerable (IUCN), is a Eurasian bird with very wide geographical range. The complete mitochondrial genome of E. aureola (16,800 bp in length) contained 37 genes (13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes) and a non-coding region (D-loop), which is similar to the typical mtDNA of vertebrates. All the protein-coding genes in E. aureola were distributed on the H-strand, except for the ND6 subunit gene and ten tRNA genes which were encoded on the L-strand.