Miracle-dz/UniFAR-FTUs huggingface dataset:
Amphibian oocyte maturation and protein synthesis: related inhibition by cyclic AMP, theophylline, and papaverine.

Two inhibitors of cyclic AMP phosphodiesterase (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17), theophylline and papaverine, inhibit the maturation of Xenopus laevis oocytes induced by four different stimuli: human chorionic gonadotropin, progesterone, testosterone, and lanthanum ions. Addition of 1 mM cyclic AMP to the medium delays maturation by approximately 2 hr. Papaverine, theophylline, and cyclic AMP inhibit amino acid incorporation into oocyte proteins by 50% or more but do not inhibit amino acid uptake. The capacity of theophylline to block maturation and protein synthesis is reversed in a parallel fashion by addition of 1-5 mM calcium ion to the medium. Addition of papaverine, theophylline, and cycloheximide to oocytes at different times after hormonal treatment shows that the step sensitive to blockage by the three drugs is coincident and precedes germinal vesicle breakdown by about 1.5 hr. Theophylline and papaverine do not increase endogenous cyclic AMP levels in oocytes but do block the decrease of cyclic AMP levels observed 3 hr after progesterone treatment. Both drugs inhibit oocyte cyclic AMP phosphodiesterase measured in vivo and severely inhibit the stimulus of calcium uptake caused by progesterone and human chorionic gonadotropin. These results suggest that cyclic AMP, theophylline, and papaverine may block oocyte maturation by inhibiting protein synthesis, possibly via a cyclic AMP-dependent protein kinase as shown in reticulocytes [Datta, A. , De Haro, C. , Sierra, J. & Ochoa, S. (1977) Proc. Natl. Acad. Sci., USA 74, 1463-1467].
Fed-state clamp stimulates cellular mechanisms of muscle protein anabolism and modulates glucose disposal in normal men.

Since maximum anabolism occurs postprandially, we developed a simulated fed state with clamped hyperinsulinemia, physiological hyperglycemia, and hyperaminoacidemia (Hyper-3) and explored muscle cellular mechanisms. Whole body [1-(13)C]leucine and [3-(3)H]glucose kinetics in healthy men were compared between hyperinsulinemic, euglycemic, isoaminoacidemic (Hyper-1, n = 10) and Hyper-3 (n = 9) clamps. In Hyper-3 vs. Hyper-1, nonoxidative leucine R(d) [rate of disappearance (synthesis)] was stimulated more (45 +/- 4 vs. 24 +/- 4 micromol/min, P < 0.01) and endogenous R(a) [rate of appearance (breakdown)] was inhibited similarly; hence net balance increased more (86 +/- 6 vs. 49 +/- 2 micromol/min, P < 0.001). Glucose R(d) was similar; thus Hyper-3 metabolic clearance rate (331 +/- 23 vs. 557 +/- 41 ml/min, P < 0.0005) and R(d)/insulin (M, 0.65 +/- 0.10 vs. 1.25 +/- 0.10 mg.min(-1). pmol(-1). l, P < 0.001) were less, despite higher insulin (798 +/- 74 vs. 450 +/- 24 pmol/l, P < 0.005). In vastus lateralis muscle biopsies, phosphorylation of Akt (P = 0.025), mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70(S6K1); P = 0.008), S6 (P = 0.049), and 4E-binding protein 1 (4E-BP1; P = 0.001) increased. With decreased eukaryotic initiation factor-4E (eIF4E). 4E-BP1 complex (P = 0.01), these are consistent with increased mTOR complex 1 (mTORC1) signaling and translation initiation of protein synthesis. Although mRNA expression of ubiquitin, MAFbx 1, and MuRF-1 was unchanged, total ubiquitinated proteins decreased 20% (P < 0.01), consistent with proteolysis suppression. The Hyper-3 clamp increases whole body protein synthesis, net anabolism, and muscle protein translation initiation pathways and decreases protein ubiquitination. The main contribution of hyperaminoacidemia is stimulation of synthesis rather than inhibition of proteolysis, and it attenuates the expected increment of glucose disposal.
Preservation of ipsilateral submandibular gland is Ill advised in cancer of the floor of the mouth or tongue

Preservation of the submandibular gland (SMG) during a neck dissection is gaining popularity and is showing an increasing tendency. The potential benefit, if the SMG is preserved, can be manifold. The aim of this study was to assess the benefit of the preservation of the SMG and the associated risk of recurrent disease in patients with oropharyngeal or oral cavity squamous cell carcinoma.
Impact of De Novo and Preexisting Inflammatory Bowel Disease on the Outcome of Orthotopic Liver Transplantation

Background:Diarrhea is a common problem in the setting of solid-organ transplantation, especially orthotopic liver transplant (OLT). De novo or preexisting inflammatory bowel disease (IBD) is one of the differential diagnoses. The aims of our study were to evaluate the frequency of de novo IBD in patients with OLT and to assess the impact of de novo IBD and preexisting IBD on the outcome of OLT. Methods:This case–control study included all eligible patients who had OLT from January 2001 to December 2009. The study group included all patients who had a biopsy-proven diagnosis of IBD after their OLT (the de novo IBD group). The control groups included patients with existing IBD before OLT and those without IBD before and after OLT. The groups were matched based on their underlying diagnoses of end-stage liver disease. Univariate and multivariate analyses were performed. Results:A total of 66 subjects were included in the study. The mean age was 45.4 ± 13.4 years, with 44 (66.7%) being male. Fifteen patients (23%) had de novo IBD, 21 (32%) had existing IBD before OLT, and 30 (45%) had no underlying IBD before or after OLT. There were no significant differences between the 2 IBD groups in any of the IBD characteristics, including IBD medications. Subjects without IBD were more likely to receive mycophenolate mofetil within 1 week of OLT than those in the de novo or preexisting IBD (70% versus 23% P = 0.018). Episodes of graft rejection were more commonly observed in subjects with preexisting IBD (52%) than de novo IBD (27%) or no IBD (20%) (P = 0.045). The rate of retransplantation was highest in the de novo IBD group followed by the preexisting IBD group and non-IBD group (20% versus 14% versus 0%; P = 0.029). Combined together, patients with IBD in the setting of OLT were more likely to be retransplanted than those without IBD (16.7% versus 0%, P = 0.045). In multivariate analysis, we found that patients with IBD were 6.7 (95% confidence interval, 1.9–23.9) times more likely to have an adverse outcome after liver transplant (P = 0.004), after adjusting for primary sclerosing cholangitis. Conclusions:De novo IBD can occur in patients after OLT. De novo IBD and preexisting IBD were found to be associated with a higher risk for graft failure, suggesting that early diagnosis and closer monitoring of the patients at risk are critical.
Effect of feldspathic ceramic surface treatments on bond strength to resin cement.

OBJECTIVE The objective of this study was to evaluate the shear bond strength of resin cement to feldspathic ceramic with various surface treatments. BACKGROUND DATA Application of adhesive techniques is well established in restorative dentistry, yet the influence of surface treatments on the bond strength of resin cement to ceramic materials prior to luting or repair procedures remains unclear. METHODS One hundred samples made of a feldspathic ceramic were divided into 10 groups (n = 10): (1) control (no treatment); (2) 10% hydrofluoric acid (HF); (3) 37% phosphoric acid (H(3)PO(4)); (4) 1.23% acidulated phosphate fluoride acid (APF); (5) diamond bur; (6) air abrasion with Al(2)O(3); (7) Al(2)O(3) + HF; (8) CoJet-Sand; (9) Er:YAG laser, and (10) Al(2)O(3) + Er:YAG laser. Afterwards, silane was applied and a resin cement cylinder was built. After 24 hours at 37 degrees C, the prepared specimens were submitted to a shear bond strength test and stereoscopic evaluation to determine the type of failure after rupture. RESULTS Bond strength means were statistically different for the different surface treatments. The highest bond strengths were obtained with HF, CoJet-Sand, and Al(2)O(3). The groups treated with Al(2)O(3) + Er:YAG laser, diamond bur, and Al(2)O(3) + HF had moderate bond strengths. The lowest bond strengths were obtained with H(3)PO(4), APF, Er:YAG laser, and the control group. CONCLUSIONS The HF, CoJet-Sand, and Al(2)O(3) techniques were the most effective surface treatments. The null surface treatment proposed with the Er:YAG laser showed low bond strength, and seems to be inadequate for clinical use with the parameters tested.
Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy

Synthesis of new proteins, a key step in the central dogma of molecular biology, has been a major biological process by which cells respond rapidly to environmental cues in both physiological and pathological conditions. However, the selective visualization of a newly synthesized proteome in living systems with subcellular resolution has proven to be rather challenging, despite the extensive efforts along the lines of fluorescence staining, autoradiography, and mass spectrometry. Herein, we report an imaging technique to visualize nascent proteins by harnessing the emerging stimulated Raman scattering (SRS) microscopy coupled with metabolic incorporation of deuterium-labeled amino acids. As a first demonstration, we imaged newly synthesized proteins in live mammalian cells with high spatial–temporal resolution without fixation or staining. Subcellular compartments with fast protein turnover in HeLa and HEK293T cells, and newly grown neurites in differentiating neuron-like N2A cells, are clearly identified via this imaging technique. Technically, incorporation of deuterium-labeled amino acids is minimally perturbative to live cells, whereas SRS imaging of exogenous carbon–deuterium bonds (C–D) in the cell-silent Raman region is highly sensitive, specific, and compatible with living systems. Moreover, coupled with label-free SRS imaging of the total proteome, our method can readily generate spatial maps of the quantitative ratio between new and total proteomes. Thus, this technique of nonlinear vibrational imaging of stable isotope incorporation will be a valuable tool to advance our understanding of the complex spatial and temporal dynamics of newly synthesized proteome in vivo.
The Role of Macrophages in the Development of Human Renal Allograft Fibrosis in the First Year After Transplantation

The aim of this study was to investigate the role of infiltrating macrophages in renal allograft fibrosis. Forty‐six protocol renal allograft biopsies obtained 1 year after transplantation were stained with Sirius red to quantify fibrosis and double stained with CD68 and CD206 to identify the proportion of alternatively activated (M2) macrophages. Biopsies were analyzed for gene expression by microarray, which was correlated with macrophage infiltration and the severity of fibrosis. The number of infiltrating CD68+ cells strongly correlated with the percentage of interstitial fibrosis (r = 0.73, p < 0.0001). Macrophage infiltration at 1 year correlated with renal dysfunction at 1, 12 and 36 months posttransplant (estimated GFR low vs. high: 1 month 78 ± 26 vs. 54 ± 19 mL/min, p < 0.01; 12 months 87 ± 29 vs. 64 ± 19 mL/min, p < 0.05; 36 months 88 ± 33 vs. 60 ± 24 mL/min, p < 0.05). Ninety‐two percent of infiltrating macrophages exhibited an M2 phenotype with CD68+ CD206+ dual staining. Gene microarrays demonstrated an alloimmune response with up‐regulation of interferon‐γ‐response genes despite the lack of rejection or inflammatory infiltrate. Consistent with this was the presence of CXCL10 in proximal tubular cells at 3 months. This suggests that M2 macrophage proliferation, or infiltration, was associated with subclinical alloimmune inflammation, tubular injury and progression of fibrosis.
Effect of pinealectomy on homocysteine levels in ovariectomized rats.

OBJECTIVE Hyperhomocysteinemia plays a role in obstetric and gynecological diseases and such diseases are seen as a consequence of an impaired methionine cycle. In the present study, it was aimed to determine the effect of estradiol and progesterone on homocysteine levels in pinealectomized and ovariectomized rats. MATERIALS AND METHODS The study was carried out on 24 adult Spraque-Dawley female rats. Rats were divided into 4 groups as follows: Group 1: Sham ovariectomy group (Sham-Ovx), Group 2: Ovariectomized and sham pinealectomized group (Ovx-Sham-Px), Group 3: Ovariectomized and pinealectomized group (Ovx-Px), Group 4: Group which were supplemented with estradiol and progesterone after ovariectomy and pinealectomy (Ovx-Px-E+P). Serum homocysteine levels were determined after experimental period. RESULTS Homocysteine levels in Group 3 were higher than those in Groups 1, 2 and 4 (p<0.05). Homocysteine levels in Groups 2 and 4 were higher than those in Group 1 (p<0.05). Homocysteine levels in Groups 2 and 4 were not different. CONCLUSION The findings of the present study demonstrate that ovariectomy lead to increases homocysteine levels. Pinealectomy in addition to ovariectomy increases homocysteine levels. However, administration of estradiol and progesterone following pinealectomy prevents the increase in homocysteine levels in ovariectomized rats.
The Insulin-Like Growth Factor Pathway in Lung Cancer

The insulin-like growth factor (IGF) pathway is involved in the normal control of fetal development, tissue growth, and metabolism. Two distinct ligands (insulin-like growth factor-1 [IGF-1] and IGF-2) plus insulin, and two receptors (insulin-like growth factor receptor-1 [IGF-1R] and the insulin receptor) capable of both homo- and heteropolymerization mediate the actions of this pathway. Cellular functions of IGF-regulated signaling are influenced by the expression of a variety of receptor docking proteins, including four different insulin receptor substrate proteins. Downstream signaling is primarily through the phosphatidylinositol-3 kinase-Akt pathway and the mitogen-activated protein kinase pathway, resulting in increased cell proliferation and apoptosis inhibition. Ligand-driven activation is influenced by upstream endocrine factors (particularly for IGF-1), imprinting (for IGF-2), by multiple circulating and tissue-based IGF-binding proteins/proteases, and by the expression of the IGF-2 clearance receptor (IGF-2R). Deregulation of IGF signaling has been described in several cancer types, including both small cell and non-small cell lung cancer. A number of IGF receptor inhibitors, including monoclonal antibodies and small molecule inhibitors are currently undergoing testing in clinical trials as both monotherapy, and in combination with chemotherapy, or with other targeted agents. Preliminary results from a randomized phase II trial of an anti-IGF-1R monoclonal antibody in combination with carboplatin/paclitaxel already suggest a potential efficacy benefit from targeting this pathway in the first line advanced non-small cell lung cancer setting.
Mental stress-induced ischemia in the laboratory and ambulatory ischemia during daily life. Association and hemodynamic features.

BACKGROUND The purpose of this study was to determine the correspondence of mental stress-induced ischemia in the laboratory with ambulatory ischemia and to assess the relationship between hemodynamic responses to mental stress and the occurrence of ischemia. Although exercise testing is usually used to elicit myocardial ischemia, ischemia during daily life usually occurs at relatively low heart rates and in the absence of strenuous physical exercise. Mental stress has been shown to trigger ischemic events in the laboratory at lower heart rates but at blood pressures comparable to exercise. We therefore compared the extent to which mental stress and exercise testing identify patients who develop ischemia out of hospital. METHODS AND RESULTS One hundred thirty-two patients with documented coronary disease and recent evidence of exercise-induced myocardial ischemia underwent 48-hour ambulatory monitoring and radionuclide ventriculography during exercise and mental stress testing. Patients who displayed mental stress-induced ischemia in the laboratory were more likely to exhibit ischemia during daily life (P < .021). Furthermore, patients who exhibited ischemia during ambulatory monitoring displayed larger diastolic blood pressure (P < .006), heart rate (P < .039), and rate-pressure product responses (P < .018) during mental stress. CONCLUSIONS Among patients with prior positive exercise stress tests, mental stress-induced ischemia, defined by new wall motion abnormalities, predicts daily ischemia independent of exercise-induced ischemia. Exaggerated hemodynamic responses during mental stress testing also identify individuals who are more likely to exhibit myocardial ischemia during daily life and mental stress.
Paramyosin is a major target of the human IgA response against Schistosoma japonicum

Human resistance and susceptibility to schistosomiasis is associated with age and specific antibody isotype responses against worm (SWAP) and egg (SEA) antigens. In a cross‐sectional study of 176 individuals infected with Schistosoma japonicum in the Philippines, strikingly similar isotype response patterns against SWAP and SEA was observed when compared to other endemic areas. Interestingly, IgA titres to SWAP correlated with older age among S. japonicum‐infected individuals (n = 176, P < 0.01), suggesting a role for this isotype in protective immunity. To identify the molecular targets of human IgA, 17 high‐IgA/SWAP responders were identified from the said population. IgA antibodies from the majority (14/17) of these individuals recognized a band of 97 kDa (Sj97), comigrating in immunoblots with the myofibrillar protein paramyosin. The antigen was confirmed as paramyosin by expressed sequence tag (EST)‐analysis of four clones obtained by screening an adult S. japonicum cDNA library with pooled IgA antisera and mouse antiparamyosin polyclonal antibodies. The identification of paramyosin as a major target of human IgA raises its potential as a vaccine candidate that targets mucosal immune responses. Since this antigen is exposed on the parasite surface only during the lung stages, we propose that human IgA contributes to parasite attrition during schistosome migration in the lungs.
Relationship Between the Number of Residency Applications and the Yearly Match Rate: Time to Start Thinking About an Application Limit?

BACKGROUND There has been an increase in the number of applications medical students have submitted for the National Residency Matching Program (NRMP). These additional applications are associated with significant costs and may contribute to match inefficiency. OBJECTIVE We explored if match rates improved in years when an increased number of applications were submitted. METHODS We analyzed yearly published data from the NRMP and the Electronic Residency Application Service for 13 specialties. A generalized linear model was used to assess the relationship between the annual match rate and the mean number of applications submitted per applicant, while controlling for the number of positions available and the number of applicants in the given year. RESULTS Over the last 13 years there has been an increase in the mean number of applications submitted per applicant (P < .001). For the 13 assessed medical specialties, there was no statistically significant relationship between the mean number of applications per applicant per year submitted to the NRMP, and the annual match rate (odds ratios near 1.00 and nonsignificant, P values > .05). CONCLUSIONS There was no improvement in the match rate in years when medical students submitted an increased number of applications. Therefore, it would appear that the applicants do not benefit from the larger number of applications submitted. Further study is required to assess the cost and benefit of these additional applications.
A model for cost-effectiveness analyses of smoking cessation interventions applied to a Quit-and-Win contest for mothers of small children

Aims: The first aim of this study was to develop a model that predicts health and economic consequences of smoking cessation in Sweden, striving to follow the methodological recommendations to reflect the societal perspective and to use the health measure quality-adjusted life-years (QALYs). The second aim was to apply the model estimates to a smoking cessation intervention. Methods: A Markov cost-effectiveness model was developed on smoking-related lung cancer, chronic obstructive pulmonary disease, and cardiovascular disease. Swedish primary data on medical treatment costs and quality-of-life weights were used, supplemented with secondary data on other societal effects and the disease and death risks. The model simulations were applied to a ``Quit-and-Win'' contest for mothers of pre-school children. In total, 238 women participated, with 34 sustained tobacco-free at 12-month follow-up. Results: The cost-effectiveness model estimates a gain of 0.34 to 0.55 QALYs (discounted 3%), and cost savings of SEK 20—35,000 per female quitter in the age range 15 to 49 years. The cost-effectiveness analyses of the intervention showed intervention costs per quitter of SEK 7,850, and intervention costs per life-years saved (YLS) (discounted 3%) of SEK 13,200. The cost-utility analysis demonstrated cost savings and a gain of 16 QALYs. Conclusions: The cost-utility analysis estimated health gains and cost savings resulting from the ``Quit-and-Win'' contest. As the model estimates on the differences in societal cost between smokers and quitters are considerable, many tobacco control programmes would result in cost savings. The construction of an optimal mix of tobacco control policies, however, demands incremental calculations on a range of programmes.
Mycoplasma pneumoniae Attachment to Glutaraldehyde-Treated Human WiDr Cell Cultures

Abstract Attachment of Mycoplasma pneumoniae to host cells initiates disease, and the attachment components may represent important protective immunogens for preventing disease. We have studied the mechanisms of attachment using in vitro cell culture systems and selected pathogenic and nonpathogenic strains of M. pneumoniae. Attachment of the pathogenic strains M129 and PI-1428 was several fold greater than attachment of the nonpathogenic strain, and attachment of strains M129 and PI-1428 was reduced by 21 to 63% when human WiDr cell monolayers were exposed to neuraminidase, supporting the concept that M. pneumoniae attaches to mammalian cells by a neuraminidase-sensitive glycoconjugate. While attachment of the two pathogenic strains was markedly reduced by treating the WiDr cells with glutaraldehyde, glutar-aldehyde treatment produced minimal effects on the attachment of the nonpathogenic strain B176. Glutaraldehyde treatment also altered the temperature dependence of attachment by the pathogenic strains. Because glutaraldehyde-treated WiDr cell monolayers showed little difference in attachment between pathogenic and nonpathogenic strains, glutaraldehyde-treated cells are not appropriate cell substrates for studying M. pneumoniae attachment mechanisms or identifying immunogens for vaccine development.