Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of thrombin as a tumor growth factor

The clinical observation that thrombosis in some patients heralds the onset of malignancy has been recognized for over a century. Thrombin the key terminal enzyme of coagulation also promotes angiogenesis and stimulates tumor-platelet adhesion, adhesion to endothelium, tumor implantation, tumor cell growth and metastasis. The thrombin receptor, a member of the protease-activated receptor family, is expressed on many tumor cell lines and on breast tumor biopsy specimens. In addition to mitogenic effects on fibroblast, smooth muscle cells and endothelial cells, thrombin also exerts direct effects on cancer cells by activation of the cell cycle through down-regulation of p27Kip1and induction of Skp2, and cyclins D and A. MicroRNA 222, which inhibits p27Kip1 , is upregulated by thrombin. In the transgenic TRAMP mouse model of prostate cancer inhibition of endogenous thrombin by hirudin retards spontaneous tumor growth. Inhibition of thrombin may lead to tumor dormancy and could explain inhibition of tumor growth and metastasis by anticoagulants observed in animal models and a beneficial effect on survival observed in some clinical trials of anticoagulants in cancer patients.
‘Bath-plug’ technique for the endoscopic management of cerebrospinal fluid leaks

Abstract In the past cerebrospinal fluid (CSF) leaks were managed via a craniotomy with intradural repair. With the advent of endoscopic sinus surgery, transnasal repair has become more popular. The comparatively low morbidity and high success rate of endoscopic repair has made it the treatment of choice for CSF leak repair. As more surgeons practice endoscopic sinus surgery, the incidence of iatrogenic CSF leaks has increased. It is important that endoscopic sinus surgeons be aware of the techniques for closing such leaks. The aim of this study is to present a new technique for the endoscopic repair of CSF leaks. Since the technique was devised the authors have used the technique on six patients. All patients had lumbar drains inserted and five patients had intra-thecal fluorescein inserted for location of the leak. All repairs have been successful with an average follow-up of 13 months. The technique consists of introducing a fat plug with a specifically secured vicryl suture into the intradural space and placing traction on the suture to seal the defect much as a bath plug seals a bath. There were no complications in any of the patients either intra- or post-operatively. The difficulties and possible complications of the technique as well as the use of a lumbar drain and intra-thecal fluorescein are discussed.
Coalescence of B cell receptor and invariant chain MHC II in a raft‐like membrane domain

The BCR binds antigen for processing and subsequent presentation on MHC II molecules. Polyvalent antigen induces BCR clustering and targeting to endocytic processing compartments, which are also accessed by Ii‐MHC II. Here, we report that clustered BCR is able to team up with Ii‐MHC II already at the plasma membrane of mouse B‐lymphocytes. Colocalization of BCR and Ii‐MHC II on the cell surface required clustering of both types of molecules. The clustering of only one type did not trigger the recruitment of the other. Ii‐bound MIF (a ligand of Ii) also colocalized with clustered BCR upon oligomerization of MIF on the surface of the B cell. Abundant surface molecules, such as B220 or TfnR, did not cocluster with the BCR. Some membrane raft‐associated molecules, such as peptide‐loaded MHC II, coclustered with the BCR, whereas others, such as GM1, did not. The formation of a BCR‐ and Ii‐MHC II‐containing membrane domain by antibody‐mediated clustering was independent of F‐actin and led to the coendocytosis of its constituents. With a rapid Brij 98 extraction method, it was possible to capture this membrane domain biochemically as a DRM. Ii and clustered BCR were present on the same DRM, as shown by immunoisolation. The coalescence of BCR and Ii‐MHC II increased tyrosine phosphorylation, indicative of enhanced BCR signaling. Our work suggests a novel role for MIF and Ii‐MHC II in BCR‐mediated antigen processing.
Enterohaemorrhagic and enteropathogenic Escherichia coli use different mechanisms for actin pedestal formation that converge on N‐WASP

Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC), two closely related diarrhoeagenic pathogens, induce actin rearrangements at the surface of infected host cells resulting in the formation of pseudopod‐like structures termed pedestals beneath intimately attached bacteria. We have shown previously that N‐WASP, a key integrator of signalling pathways that regulate actin polymerization via the Arp2/3 complex, is essential for pedestal formation induced by EPEC using N‐WASP‐defective cell lines. Here we show that actin pedestal formation initiated by EHEC also depends on N‐WASP. Amino acid residues 226–274 of N‐WASP are both necessary and sufficient to target N‐WASP to sites of EHEC attachment. The recruitment mechanism thus differs from that used by EPEC, in which amino‐terminal sequences of N‐WASP mediate recruitment. For EPEC, recruitment of N‐WASP downstream of Nck has been postulated to be mediated by WIP. However, we find a direct interaction of N‐WASP with WIP to be dispensable for EPEC‐induced pedestal formation and present data supporting an F‐actin‐dependent localization of WIP to actin pedestals induced by both EPEC and EHEC. In summary, our data show that EPEC and EHEC use different mechanisms to recruit N‐WASP, which is essential for actin pedestal formation induced by both pathogens.
Promotion of skeletal muscle repair in a rat skeletal muscle injury model by local injection of human adipose tissue‐derived regenerative cells

Human adipose tissue‐derived regenerative cells (ADRCs) can be isolated easily and aseptically from unwanted subcutaneous fat without culturing. ADRCs have been used in clinical cosmetic therapy. In addition, they are expected to be an attractive and feasible source of cell‐based therapies in regenerative medicine. Therefore, this paper investigates whether transplantation of human adult ADRCs into skeletal muscle injury models promotes the repair of muscle tissues. This was done by locally injecting human ADRCs into an injured site after laceration of the nude‐rat tibialis anterior muscle. Phosphate‐buffered saline (PBS) and bone marrow mononuclear cells (MNCs) were injected as negative and positive controls, respectively. After injury, recovery of muscle strength was accelerated by transplantation of ADRCs compared to administration of PBS and MNCs. Moreover, transplantation of ADRCs also enhanced angiogenesis and myogenesis, but the number of vascular and muscular cells labeled with the human cell‐specific maker was limited at the injury site. Results showed that transplantation of ADRCs into a skeletal muscle injury model promoted repair of muscle tissues in a paracrine manner rather than differentiation of itself into blood vessels and myofibres. Thus, it is believed that ADRCs are a useful and feasible cell source not only for cosmetic therapy but also for regenerative therapy. Copyright © 2012 John Wiley & Sons, Ltd.
Nasal Obstruction and Sleep-disordered Breathing: The Effect of Supine Body Position on Nasal Measurements in Snorers

Objective --Nasal obstruction is considered to be a potential etiological factor in sleep-disordered breathing. However, a significant correlation between nasal measurements and obstructive sleep apnea has not been demonstrated so far. The aim of this study was to investigate the relationships between nasal resistance, nasal volumes and selected sleep parameters using nasal measurements performed in both seated and supine positions. We also investigated whether snoring patients in our clinical sample showed increased positional or decongestive nasal mucosal changes. Material and Methods --Forty-one snoring men on a waiting list for correction of nasal obstruction underwent polysomnography, anterior rhinomanometry and acoustic rhinometry. Nineteen non-snoring control subjects were also recruited. Nasal measurements were performed in a seated position, after lying down in a supine position and, after decongestion of nasal mucosa, in a seated position again. Results --In the overall patient group, nasal volume at a distance 2-4 cm from the nares in the supine position correlated inversely with apnea-hypopnea index (AHI) ( r = m 0.32, p <0.05) and oxygen desaturation index (ODI) ( r = m 0.49, p <0.05). In the non-obese patients, total nasal resistance measured in a supine position correlated with AHI ( r =0.50, p <0.05) and ODI ( r =0.58, p <0.05) and supine nasal volumes were also inversely correlated with ODI. No significant correlations were found between baseline nasal measurements performed in a seated position and sleep parameters. Postural or decongestive changes in nasal measurements were not increased in snoring patients compared with control subjects. Conclusion --The relationship found between nasal measurements and sleep parameters suggests that nasal obstruction does augment airway collapse.
Ki‐67 index enhances the prognostic accuracy of the urothelial superficial bladder carcinoma risk group classification

Approximately 80% of bladder tumors are urothelial superficial papillary carcinomas (USPC). Despite a generally good prognosis, these tumors have a strong propensity to recur and about 1/3 of them compared to disease progression. Histological assessment of these superficial tumors is not sufficiently discriminator in predicting prognosis; therefore, we decided to evaluate the prognostic significance of p53 and Ki‐67 immunoexpression in low‐grade (GI‐II) USPC in order to predict the potential outcome of these tumors. P53 and Ki‐67 immunoexpression were studied in function of recurrence‐free and progression‐free survival in 159 primary superficial bladder tumors. A prognostic risk model based on grade, stage and multifocality was also evaluated. P53 accumulation was significantly related to tumor progression (p=0.006). High Ki‐67 index (≥18%) and multifocality were significantly related to recurrence (both p=0.0001) and progression‐free survival (both p=0.0001) and were independent prognostic factors in the multivariate analysis. The prognostic risk model based on grade, stage and multifocality was not an efficient discriminator of outcome. Adding the Ki‐67 index into the risk model, single pTa/T1‐GI Ki‐67 positive tumors, usually classified as low risk, were reclassified as of intermediate risk. After this reclassification, the risk group model identified a subgroup of pTa/T1‐G1 with a high risk of recurrence and progression. Ki‐67 index is a reliable prognostic marker in urothelial superficial bladder carcinoma and, when included into a risk profile classification of the low‐grade USPC, the accuracy of the prognostic discrimination is enhanced. © 2003 Wiley‐Liss, Inc.
Antiproliferative Activity of Aqueous Leaf Extract of Annona muricata L. on the Prostate, BPH-1 Cells, and Some Target Genes

Background. Annona muricata L. has been reported to possess antitumor and antiproliferative properties. Not much work has been done on its effect on BPH-1 cell lines, and no in vivo studies targeting the prostate organ exist. The study determined the effect of A muricata on human BPH-1 cells and prostate organ. Methods. The MTT assay was performed on BPH-1 cells using the aqueous leaf extract of A muricata. Cells (1 × 105 per well) were challenged with 0.5, 1.0, and 1.5 mg/mL extract for 24, 48, and 72 hours. Cell proliferation and morphology were examined microscopically. BPH-1 cells (1 × 104 per well) were seeded into 6-well plates and incubated for 48 hours with 0.5, 1.0, and 1.5 mg/mL A muricata extract. Reverse transcriptase polymerase chain reaction was performed using mRNA extracted from the cells. Possible target genes, Bax and Bcl-2, were examined. Twenty F344 male rats (≈200 g) were gavaged 30 mg/mL (10 rats) and 300 mg/mL (10 rats) and fed ad libitum alongside 10 control rats. Rats were sacrificed after 60 days. The prostate, seminal vesicles, and testes were harvested for histological examination. Results. Annona muricata demonstrated antiproliferative effects with an IC50 of 1.36 mg/mL. Best results were obtained after 48 hours, with near cell extinction at 72 hours. Bax gene was upregulated, while Bcl-2 was downregulated. Normal histological architecture was observed for all testes. Seminal vesicle was significantly reduced in test groups (P < .05) and demonstrated marked atrophy with increased cellularity and the acinii, empty of secretion. Prostate of test groups were reduced with epithelial lining showing pyknotic nucleus, condensation, and marginalization of the nuclear material, characteristic of apoptosis of the glandular epithelium. Furthermore, scanty prostatic secretion with flattening of acinar epithelial lining occurred. Conclusion. Annona muricata has antiproliferative effects on BPH-1 cells and reduces prostate size, possibly through apoptosis.
Background factors of enamel focal demineralization in groups of Finnish and Russian children.

The aim of this study was to analyze the occurrence of EFD lesions in relation to some background factors in Finnish and Soviet children. Children aged 7, 9 and 12 years (n = 1187) were examined clinically in Helsinki, Kuopio (Finland), Moscow and Leningrad (USSR). A questionnaire sent to the parents was used to collect data on toothbrushing frequency, use of sweets, cakes, soft drinks, sugar-sweetened tea/coffee and mother's education. In addition to bivariate analysis, log-linear regression models were used for comparing the simultaneous association in two ethnic groups. In general, the Finnish children had more EFD lesions than the Soviet children did. Among the Finns no consistent associations were found between the number of EFD lesions and the use of different sugar products or differences in toothbrushing habits. The number of EFD lesions decreased consistently according to mother's education with the Finnish children, but not with the Soviet children. The final multivariate model for Finnish children included age, toothbrushing frequency, place of residence (Kuopio) and use of soft drinks. The respective model for the Soviet children included age and place of residence (Leningrad). Evidently, the demineralization process or tooth resistance differs in these two ethnic groups.
Muscarinic Receptor Activation Protects Cells from Apoptotic Effects of DNA Damage, Oxidative Stress, and Mitochondrial Inhibition*

The impact of muscarinic receptor stimulation was examined on apoptotic signaling induced by DNA damage, oxidative stress, and mitochondrial impairment. Exposure of human neuroblastoma SH-SY5Y cells to the DNA-damaging agent camptothecin increased p53 levels, activated caspase-3, and caused cell death. Pretreatment with oxotremorine-M, a selective agonist of muscarinic receptors that are expressed endogenously in these cells, did not affect the accumulation of p53 but greatly attenuated caspase-3 activation and protected from cell death to nearly the same extent as treatment with a general caspase inhibitor. Treatment with 50–200 μmH2O2 caused the activation of caspase-3 beginning after 2–3 h, followed by eventual cell death. Oxotremorine-M pretreatment protected cells from H2O2-induced caspase-3 activation and death, and this was equivalent to protection afforded by a caspase inhibitor. Muscarinic receptor stimulation also protected cells from caspase-3 activation induced by exposure to rotenone, a mitochondrial complex 1 inhibitor, but no protection was evident from staurosporine-induced caspase-3 activation. The mechanism of protection afforded by muscarinic receptor activation from camptothecin-induced apoptotic signaling involved blockade of mitochondrial cytochrome c release associated with a bolstering of mitochondrial bcl-2 levels and blockade of the translocation of Bax to mitochondria. Likely the most proximal of these events to muscarinic receptor activation, mitochondrial Bax accumulation, also was attenuated by oxotremorine-M treatment after treatment with H2O2 or rotenone. These results demonstrate that stimulation of muscarinic receptors provides substantial protection from DNA damage, oxidative stress, and mitochondrial impairment, insults that may be encountered by neurons in development, aging, or neurodegenerative diseases. These findings suggest that neurotransmitter-induced signaling bolsters survival mechanisms, and inadequate neurotransmission may exacerbate neuronal loss.
Thermography as a quantitative imaging method for assessing postoperative inflammation.

OBJECTIVE To assess differences in skin temperature between the operated and control side of the face after mandibular third molar surgery using thermography. METHODS 127 patients had 1 mandibular third molar removed. Before the surgery, standardized thermograms were taken of both sides of the patient's face using a Flir ThermaCam™ E320 (Precisions Teknik AB, Halmstad, Sweden). The imaging procedure was repeated 2 days and 7 days after surgery. A region of interest including the third molar region was marked on each image. The mean temperature within each region of interest was calculated. The difference between sides and over time were assessed using paired t-tests. RESULTS No significant difference was found between the operated side and the control side either before or 7 days after surgery (p > 0.3). The temperature of the operated side (mean: 32.39 °C, range: 28.9-35.3 °C) was higher than that of the control side (mean: 32.06 °C, range: 28.5-35.0 °C) 2 days after surgery [0.33 °C, 95% confidence interval (CI): 0.22-0.44 °C, p < 0.001]. No significant difference was found between the pre-operative and the 7-day post-operative temperature (p > 0.1). After 2 days, the operated side was not significantly different from the temperature pre-operatively (p = 0.12), whereas the control side had a lower temperature (0.57 °C, 95% CI: 0.29-0.86 °C, p < 0.001). CONCLUSIONS Thermography seems useful for quantitative assessment of inflammation between the intervention side and the control side after surgical removal of mandibular third molars. However, thermography cannot be used to assess absolute temperature changes due to normal variations in skin temperature over time.
Functional analysis of the Zygosaccharomyces rouxii Fps1p homologue

The osmotolerant yeast Zygosaccharomyces rouxii accumulates the polyols glycerol and D‐arabitol intracellularly in response to hyperosmotic stress, but the membrane transport proteins regulating polyol accumulation have not been studied. We have cloned and characterized a FPS1 homologue in Z. rouxii NRRL Y2547, and its sequence revealed a 2709 bp open reading frame encoding a peptide of 692 deduced amino acids with 56.9% identity to the Saccharomyces cerevisiae Fps1p. The role of this putative membrane channel protein in polyol accumulation and release during osmoregulation was investigated. The Z. rouxii FPS1 (ZrFPS1) complemented the S. cerevisiae fps1Δ growth defect and glycerol release upon hypo‐osmotic shock. Deletion of ZrFPS1 did not affect growth on glycerol as sole carbon source, suggesting that other transport proteins are involved in the uptake of glycerol. However, mutants lacking ZrFPS1 exhibited a significant decrease in glycerol and D‐arabitol efflux and poor growth during hypo‐osmotic conditions, suggesting that ZrFPS1 might be involved in D‐arabitol transport in addition to glycerol. This is the first demonstration of a yeast gene that affects D‐arabitol transport. The full‐length ZrFPS1 gene sequence including upstream promoter has been deposited in the public database under Accession No. AY488133. Copyright © 2005 John Wiley & Sons, Ltd.
EPIRETINAL PROLIFERATION SEEN IN ASSOCIATION WITH LAMELLAR MACULAR HOLES: A Distinct Clinical Entity

Purpose: To describe the prevalence and imaging characteristics of a distinct entity of epiretinal proliferation seen predominantly in association with lamellar macular holes (LMH), termed lamellar hole–associated epiretinal proliferation (LHEP). Methods: Retrospective observational case review of 2,030 eyes of 1,104 patients with diagnoses including LMH, full-thickness macular hole, and epiretinal membrane (ERM) imaged with spectral domain optical coherence tomography (SD-OCT) from 2008 to 2013. Lamellar hole–associated epiretinal proliferation, defined on SD-OCT imaging as an epiretinal material of homogenous medium reflectivity, was identified and its features were qualitatively compared against conventional ERM using the SD-OCT data. Results: Lamellar hole–associated epiretinal proliferation was found in 68 of 2,030 eyes (3.3%), of which 88.2% had LMH and 11.8% had full-thickness macular hole. Lamellar hole–associated epiretinal proliferation was found in 60 of 197 eyes (30.5%) with LMH and 8 of 99 eyes (8.0%) with full-thickness macular hole. Lamellar hole–associated epiretinal proliferation was not seen in 1,734 eyes with ERM, which had no inner retinal defects detectable on SD-OCT. Lamellar hole–associated epiretinal proliferation appeared as a substantial material of homogenous medium reflectivity on the epiretinal surface that demonstrated contiguity with the middle retinal layers and conformed to the adjacent retinal anatomy. Of the eyes with LHEP and LMH, 98% had splitting of the retina in the region of Henle's fiber layer in the area immediately around the partial thickness hole, whereas 88% had visible connecting tissue from the base of the lamellar hole to the proliferating epiretinal tissue. In contrast to ERM, LHEP did not induce tractional effects such as distortion or edema of the underlying normal retinal tissue. Morphologic stability was demonstrated in 97% of eyes containing LHEP in serial eye-tracked SD-OCT images for up to 63 months of retrospective follow-up. Conclusion: Spectral domain optical coherence tomography imaging showed that a subset of patients with LMH had an epiretinal proliferation with medium reflectivity and no evidence of contractile properties that was contiguous with layers of the mid-retina. This phenotype differs from conventionally described ERMs in appearance and induced changes of the underlying retina. Given these distinct anatomical relationships, the presence of LHEP could affect surgical outcomes.
Dietary creatine supplementation and muscular adaptation to resistive overload.

PURPOSE This study examined the influence of dietary creatine (CR) supplementation upon mechanical and hypertrophic responses to a well-defined conditioning stimulus provided by electromyostimulation (EMS). METHODS Eighteen resistance-trained subjects were assigned CR or a placebo (PL) in a randomized, double-blind fashion. After CR loading (20 g x d(-1) for 7 d), CR supplementation (5 g x d(-1)) or PL was continued for 8 wk. During supplementation, EMS (3--5 sets of 10 coupled eccentric and concentric actions) was applied to the left m. quadriceps femoris (QF) twice weekly while subjects continued voluntary resistance training of both lower limbs unsupervised. Cross-sectional area (CSA) of each QF was assessed with magnetic resonance imaging (MRI). Torque during EMS was analyzed to assess muscle loading and fatigue resistance. RESULTS Maximal torque and the torque time integral increased markedly over training (P < or = 0.0001). These responses reflected activation of more muscle as EMS current was increased (about 16%), greater recovery between sets (P < or = 0.0423), and less fatigue during sets over training (P = 0.0002). CR did not influence these responses (P = 0.8093). In accord with these results, the increase in CSA for the stimulated QF (11%) was comparable for CR and PL (P = 0.2190). CSA in the nonstimulated QF increased 5% in CR (P = 0.0091) but did not change in PL. CONCLUSION We conclude that CR supplementation did not augment the mechanical or hypertrophic response to a precisely measured conditioning stimulus that attenuated but did not ameliorate fatigue. We suggest that enhanced fatigue resistance may not explain the apparent ergogenic effect of CR during voluntary training.