Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of a 74-kDa Nuclear Factor 1 (NF1) Protein Is Induced in Mouse Mammary Gland Involution

Testosterone repressed prostate message-2 (TRPM-2)/clusterin gene expression is rapidly induced in early involution of the mouse mammary gland, after weaning, and in the rat ventral prostate, after castration. A search for involution-enhanced DNaseI footprints in the proximal mouse TRPM-2/clusterin gene promoter led to the identification and characterization (by DNase I footprinting and EMSA) of a twin nuclear factor 1 (NF1) binding element at −356/−309, relative to the proposed transcription start site; nuclear extracts from 2-day involuting mouse mammary gland showed an enhanced footprint over the proximal NF1 element; extracts from involuting prostate showed enhanced occupancy of both NF1 binding elements. Subsequent EMSA and Western analysis led to the detection of a 74-kDa NF1 protein whose expression is triggered in early involution in the mouse mammary gland; such an induced protein is not found in the involuting rat ventral prostate. This protein was not found in lactation where three other NF1 proteins of 114, 68, and 46 kDa were detected. Reiteration of the epithelial cell apoptosis associated with early mammary gland involution, in vitro, in a primary cell culture system, triggered the appearance of the 74-kDa NF1. Overlaying the cells with laminin-rich extracellular matrix suppressed the apoptosis and the expression of the 74-kDa NF1 and, in the presence of lactogenic hormones, initiated milk protein gene expression and the expression of two of the lactation-associated NF1 proteins (68 and 46 kDa). This study, thus, identifies for the first time the occurrence of a switch in expression of different members of the family of NF1 transcription factors as mammary epithelial cells move from the differentiated to the involution/apoptotic state, and it is likely that the involution-specific 74-kDa NF1 accounts for the enhanced NF1 footprint detected on the TRPM-2/clusterin promoter with extracts of mouse mammary gland.
CDKAL1 and HHEX are associated with type 2 diabetes‐related traits among Yup'ik people (在尤皮克人群中CDKAL1和HHEX与2型糖尿病相关特征有关)

Genome‐wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D), mainly among individuals of European ancestry. In the present study, we examined the frequency of these SNPs and their association with T2D‐related traits in an Alaska Native study population with a historically low prevalence of T2D. We also investigated whether dietary characteristics that may protect against T2D, such as n‐3 polyunsaturated fatty acid (PUFA) intake, modify these associations.
Methacholine inhalation challenge: a shorter, cheaper and safe approach.

Increased nonspecific bronchial hyperresponsiveness to pharmacological agents such as histamine or methacholine (MCh) is a hallmark of asthma. The measurement of airway reactivity is quite sensitive but testing is tedious, and time and money consuming. The present aim was, therefore, to design the shortest possible, yet safe inhalation challenge protocol applicable for a lung function referral centre. All records of studies performed in our institution during 1996 were analyzed retrospectively with a baseline ratio (bl) of forced expiratory volume in one second/forced vital capacity (FEV1/FVC) > or = 0.7 (n=449). It was questioned what the initial dose should be, and whether some inhalation steps could have been skipped without losing pertinent information and/or causing an adverse response (a fall in FEV1 >40%). When unavailable, provocative dose causing a 20% fall in FEV1 (PD20) values were obtained by linear inter- or extrapolation of the existing data. The present study showed that three-fold concentration steps could have been employed with minimal change in outcome. Only 151449 patients (3.3%) would have experienced a severe response. Five subjects (of 169, 3.0%) with FEV1/FVCbl 0.7-0.8 reacted to inhalation up to 0.073 micromol. Four subjects (of 280, 1.4%) with FEV1/ FVCbl> or =0.8 reacted to inhalation up to 0.219 micromol. The authors suggest that: 1) an initial dose of 0.219 micromol (initial concentration= 0.21 mg.mL(-1)) may be used when the baseline ratio of forced expiratory volume in one second to forced vital capacity > or =0.8 and 0.073 micromol (initial concentration=0.07 mg.mL(-1)) when the baseline ratio is <0.8; 2) a tripling dose protocol is easier to perform, cheaper and 30.2%, faster, yet just as safe; and 3) other abbreviated protocols used in epidemiologic settings may not be applicable in a referral centre setting.
Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor).

PURPOSE To determine the clinical efficacy of imatinib in patients with advanced aggressive fibromatosis (AF) and to identify the molecular basis of response/nonresponse to this agent. PATIENTS AND METHODS Nineteen patients with AF were treated with imatinib (800 mg/d) as part of a phase II clinical study. Tumor specimens were analyzed for mutations of KIT, PDGFRA, PDGFRB, and CTNNB1 (beta-catenin). Tumor expression of total and activated KIT, PDGFRA, and PDGFRB were assessed using immunohistochemistry and immunoblotting techniques. We also measured plasma levels of PDGF-AA and PDGF-BB in patients and normal patient controls. RESULTS Three of 19 patients (15.7%) had a partial response to treatment, with four additional patients having stable disease that lasted more than 1 year (overall 1 year tumor control rate of 36.8%). No mutations of KIT, PDGFRA, or PDGFRB were found. Sixteen of 19 patients (84%) had mutations involving the WNT pathway (APC or CTNNB1). However, there was no correlation between WNT pathway mutations and clinical response to imatinib. AF tumors expressed minimal to null levels of KIT and PDGFRA but expressed levels of PDGFRB that are comparable with normal fibroblasts. However, PDGFRB phosphorylation was not detected, suggesting that PDGFRB is only weakly activated. AF patients had elevated levels of PDGF-AA and PDGF-BB compared with normal patient controls. Notably, the plasma level of PDGF-BB was inversely correlated with time to treatment failure. CONCLUSION Imatinib is an active agent in the treatment of advanced AF. Imatinib response in AF patients may be mediated by inhibition of PDGFRB kinase activity.
Nanomolar concentrations of kynurenic acid reduce extracellular dopamine levels in the striatum

Precise regulation of dopaminergic activity is of obvious importance for the physiology and pathology of basal ganglia. We report here that nanomolar concentrations of the astrocyte‐derived neuroinhibitory metabolite kynurenic acid (KYNA) potently reduce the extracellular levels of striatal dopamine in unanesthetized rats in vivo. This effect, which is initiated by the KYNA‐induced blockade of α7 nicotinic acetylcholine receptors, highlights the functional relevance of glia–neuron interactions in the striatum and indicates that even modest increases in the brain levels of endogenous KYNA are capable of interfering with dopaminergic neurotransmission.
Structural Features of the Nerve Growth Factor Inducible Large External Glycoprotein of PC12 Pheochromocytoma Cells and Brain

Abstract: We have examined the oligosaccharide structure of a major Mr= 230,000 cell surface glycoprotein from rat PC12 pheochromocytoma cells, and of the immunochemically cross‐reactive species present in brain. In response to nerve growth factor (NGF) the PC12 cells extend long processes and acquire other properties similar to those of differentiated sympathetic neurons. These morphological changes are accompanied by a 3‐ to 5‐fold increase in the concentration and labeling of this cell surface glycoprotein, which has previously been named the NGF‐inducible large external, or NILE, glycoprotein. Tri‐ and tetraantennary complex oligosaccharides are the predominant carbohydrate units present in the NILE glycoprotein from both brain and PC12 cells, where they represent 77–90% of the biosynthetically labeled oligosaccharides. Most of these are not substituted by fucose on the core N‐acetylglucosamine which is linked to asparagine, and are accompanied by smaller proportions of biantennary and high‐mannose oligosaccharides. Sequential lectin‐agarose affinity chromatography employing concanavalin A, lentil lectin, and the leukoagglutinating lectin of Phaseolus vulgaris, together with neuraminidase treatment of the fractionated glycopeptides, demonstrated a moderate degree of microheterogeneity among the predominant tri‐ and tetraantennary oligosaccharide units with respect to the presence of core fucose, outer galactose and sialic acid residues, and the substitution positions on the α‐linked mannose residues. NGF treatment of the PC12 cells had no significant effect on the oligosaccharide structure of the NILE glycoprotein. The greater molecular size of the PC12 cell NILE glycoprotein as compared to the immunochemically cross‐reactive species present in brain (Mr= 205,000) is apparently due to the greater size of the PC12 cell tri‐ and tetraantennary complex oligosaccharides.
Repeated fluorescence in situ hybridization by a microwave‐enhanced protocol

A novel re‐hybridization protocol for pathology archive sections that uses microwave‐assisted fluorescence in situ hybridization (FISH) is described. Stripping the probe from the pathology archive sections with HCl and re‐hybridizing with the next probe by intermittent microwave irradiation generated clear signals without background noise. Repeated stripping and hybridization with numerous bacterial artificial chromosome (BAC)‐derived probes would identify the profile of genome‐wide changes in small lesions on sections.
Diagnosis of occult scaphoid fractures: a randomized, controlled trial comparing bone scans to radiographs for diagnosis.

BACKGROUND Many patients with suspected scaphoid fractures but negative radiographs are immobilized for ≥ 2 weeks and are eventually found to have no fracture. Bone scans are reportedly 99% sensitive for these injuries if done ≥ 72 hours postinjury. OBJECTIVE The purpose of this study was to determine if early bone scans would allow for shorter cast immobilization periods in patients with suspected scaphoid fractures. METHODS Twenty-seven patients with clinically suspected scaphoid fractures and negative radiographs were randomized to early diagnosis (bone scan within 3-5 days; n = 12) or traditional diagnosis (radiographs 10-14 days postinjury; n = 15). The primary outcome was number of days immobilized in a cast. RESULTS The mean number of days immobilized was 26 in the traditional group and 29 in the bone scan group. Overall, 6 patients had scaphoid fractures (2 in the traditional diagnosis group and 4 in the bone scan group; p > 0.05), and 8 had other types of fractures. These other types of fractures included four distal radius fractures, two triquetral fractures, one trapezoid fracture, and one hamate fracture. There was no significant difference in the number of other types of fractures between groups. The Kaplan-Meier survival analysis using the log-rank test revealed that there was no statistically significant difference between days immobilized between the radiograph and bone scan groups (p = 0.38). CONCLUSIONS The current study suggests that the use of bone scans to help diagnose occult scaphoid fractures does not reduce the number of days immobilized and that the differential diagnosis of occult scaphoid fractures should remain broad because other injuries are common.
Comparison of extended-release epidural morphine with femoral nerve block to patient-controlled epidural analgesia for postoperative pain control of total knee arthroplasty: a case-controlled study.

BACKGROUND Because newer anticoagulation strategies for total knee replacement present potentially increased risk of neuraxial analgesia, there is movement away from using patient-controlled epidural analgesia (PCEA) for pain control. This concern opens the door for other regional modalities in postoperative analgesia, including the use of extended-release epidural morphine (EREM) combined with a femoral nerve block (FNB). METHODS This study was a prospective observational chart review with the use of recent historical controls in patients undergoing unilateral total knee replacement. Outcomes of interest were 0-, 24-, and 48-hour postoperative pain scores using the visual analog scale (VAS); incidence of side effects; and time spent in the postanesthesia care unit (PACU). RESULTS Postoperative pain scores at 24 and 48 hours in the EREM and FNB group (n = 14; 2.6 ± 0.6 and 5.0 ± 0.9, respectively) were comparable to the PCEA group (n = 14; 3.8 ± 0.6 and 4.2 ± 0.9). The PACU time was shorter in the EREM and FNB group (2.4 ± 0.3 hours) compared with PCEA (3.6 ± 0.3 hours, P = .02). No statistically significant difference was found in the incidence of side effects between the 2 groups. CONCLUSIONS The VAS scores at 24 and 48 hours indicate that EREM and FNB provide comparable analgesia to PCEA. The trend toward shorter PACU times represents an opportunity for cost-identification analysis. The study data are limited by their observational nature and the small number of patients involved; nevertheless, this study demonstrates a therapeutic equivalence to PCEA that may be more cost effective.
mTOR Controls Cell Cycle Progression through Its Cell Growth Effectors S6K1 and 4E-BP1/Eukaryotic Translation Initiation Factor 4E

ABSTRACT The mammalian target of rapamycin (mTOR) integrates nutrient and mitogen signals to regulate cell growth (increased cell mass and cell size) and cell division. The immunosuppressive drug rapamycin inhibits cell cycle progression via inhibition of mTOR; however, the signaling pathways by which mTOR regulates cell cycle progression have remained poorly defined. Here we demonstrate that restoration of mTOR signaling (by using a rapamycin-resistant mutant of mTOR) rescues rapamycin-inhibited G1-phase progression, and restoration of signaling along the mTOR-dependent S6K1 or 4E-BP1/eukaryotic translation initiation factor 4E (eIF4E) pathways provides partial rescue. Furthermore, interfering RNA-mediated reduction of S6K1 expression or overexpression of mTOR-insensitive 4E-BP1 isoforms that block eIF4E activity inhibit G1-phase progression individually and additively. Thus, the activities of both the S6K1 and 4E-BP1/eIF4E pathways are required for and independently mediate mTOR-dependent G1-phase progression. In addition, overexpression of constitutively active mutants of S6K1 or wild-type eIF4E accelerates serum-stimulated G1-phase progression, and stable expression of wild-type S6K1 confers a proliferative advantage in low-serum-containing media, suggesting that the activity of each of these pathways is limiting for cell proliferation. These data demonstrate that, as for the regulation of cell growth and cell size, the S6K1 and 4E-BP1/eIF4E pathways each represent critical mediators of mTOR-dependent cell cycle control.
Channel model for in-body WBAN

This paper presents an experimental investigation into the in-body channel in 400 MHz MICS Band. By taking into account the joint effect of human movement and multipath effects, the measurements have been conducted in a populated office at very short distances. The dynamic channel behaviour has been captured and based on the statistical analyses of fading duration, a six-state Semi-Markov model that considers both Line of Sight (LOS) and Non Line of Sight (NLOS) cases is proposed. Parameters of the Semi-Markov model are estimated from the measured data. The validity of this model is confirmed by comparison of the first order and second order statistics of the proposed model with the measured data.
Activated charcoal enhanced the antigen-expression and dendritic cell maturation of the vaccine using Listeria-platform.

BACKGROUND Listeria monocytogenes (LM) has been used as a vaccine vector based upon its ability to induce a strong cell-mediated immune response. LM inactivated with γ-irradiation retains immunogenic properties and is an attractive platform for clinical use since it would have improved safety concerns compared to live vectors. Activated charcoal has been shown to enhance expression of LM proteins such as PrfA. AIM To investigate the effect of various growth conditions supplemented with activated charcoal on recombinant antigen expression. METHODS We prepared γ-irradiated ovalbumin-expressing LM (LM-OVA) after growth under various culture conditions. We cultured LM-OVA at various temperatures including 25°C, 37°C and 37°C with activated charcoal and compared OVA expression by western blot analysis, dendritic cells maturation and OVA-specific T cells. RESULTS The OVA expression was highest in γ-irradiated LM-OVA grown with activated charcoal at 37°C. Compared to other growth conditions, γ-irradiated LM-OVA grown with activated charcoal at 37°C induce better DC maturation as well as production of the highest number of antigen-specific IFN γ-secreting T cells. CONCLUSION The further study should be demonstrated the potential to alter growth conditions to enhance OVA expression resulting for vaccine vectors, thereby improving their safety and efficacy.
17 Beta-estradiol increases VEGF receptor-2 and promotes DNA synthesis in retinal microvascular endothelial cells.

PURPOSE Estrogen is known to promote angiogenesis in gonads. The presence of estrogen receptors in the vascular endothelium of organs other than gonads has been reported. The goal of this study was to determine whether estrogen promotes the proliferation of retinal microvascular endothelial cells and to explore the mechanism of it. METHODS DNA was quantitated using primary cultures of bovine retinal endothelial cells that were incubated with different doses of 17 beta-estradiol (E2), VEGF, or both. The changes in expression level of VEGF and VEGF receptor-2 (VEGFR2) were measured using northern blot analysis after treatment with E2. The presence of estrogen receptors in the endothelial cells was studied by immunohistochemistry and western blot analysis. RESULTS 17 Beta-estradiol (E2) increased the DNA level in bovine retinal capillary endothelial cells (BRECs) by 177% at 1 nM (P < 0.05) and 150% at 10 nM (P < 0.05) by comparison with unstimulated BREC. One hundred nanomole tamoxifen completely blocked the E2-induced DNA synthesis in BRECs. Ten nanomole E2 augmented vascular endothelial growth factor (VEGF)-induced DNA synthesis in BRECs significantly (160%, P < 0.01). Ten nanomole E2 also increased VEGF mRNA expression, which peaked after 24 hours (6.7 times, P < 0.05), and VEGF receptor-2 (VEGFR2) mRNA expression, which peaked after 9 hours (2.4 times, P < 0.05). The mRNA expression level of VEGFR2 peaked with 10 nM E2 (P < 0.05) and that of VEGF reached maximum with 1 nM E2 (15 times, P < 0.001). VEGFR2 and VEGF proteins increased in parallel with their mRNA levels. Immunocytochemistry showed estrogen receptor expression in BRECs, and western blot analysis indicated the presence of a 67-kDa protein that was compatible with the estrogen receptor. CONCLUSIONS These findings suggest that E2 may stimulate BREC growth by the receptor-mediated pathway and that E2 may augment the VEGF-dependent angiogenesis partly through the upregulation of VEGFR2.
Oral Arginine Reduces Systemic Blood Pressure in Type 2 Diabetes: Its Potential Role in Nitric Oxide Generation

Objectives: Arginine is converted in the endothelial cells to nitric oxide (NO) and citrulline. NO is a potent vasodilator in humans, but diabetics may have a reduced generation of NO which results in endothelial dysfunction. The aim of this study was to evaluate the effects of oral arginine on nitric oxide production, counter-regulatory hormones and blood pressure in mildly hypertensive type 2 diabetic patients. Methods: A prospective, crossover clinical trial was performed over a three-day stay in the General Clinical Research Center. Six patients with type 2 diabetes mellitus and mild hypertension consented and were given orally three grams of arginine per hour for 10 hours on either day 2 or day 3. On both days 2 and 3, blood pressure was monitored between 5 AM and 4 PM and mean pressure determined. Results: Oral arginine increased plasma citrulline from 31.3 ± 6.0 to 41.5 ± 6.0 μmol/L (mean ± SEM; p < 0.05) which may reflect an increased conversion of arginine into NO and citrulline. Arginine reduced systolic BP from 135 ± 7 to 123 ± 8 mmHg; p < 0.05. Diastolic BP fell from 86.9 ± 1.7 to 80.7 ± 2.4 mmHg; p < 0.05). The reduction in BP was noted to occur two hours after starting oral arginine, and BP returned to normal within one hour of stopping the arginine. The oral arginine had no effect on C-peptide, insulin or other hormone concentrations. Conclusions: These data suggest that oral arginine may increase endothelial nitric oxide synthase (NOS) to increase vascular NO and temporally reduce blood pressure in mildly hypertensive type 2 diabetic patients.
Relationship between proliferative activity and estrogen receptors in breast cancer

The proliferative activity of breast cancer has been analyzed in relation to the hormonal characteristics of the host and of the tumor for 199 patients. The analyses of labeling index frequency distributions of estrogen receptor positive (ER+) and negative (ER‐) cancers from premenopausal and postmenopausal patients have allowed us to identify three different kinetic groups. A first group, with a very low proliferative acitivty, includes ER+ cancers from postmenopausal patients; a second group, with an intermediate proliferative activity, includes ER+ cancers from premenopausal and ER‐ cancers from postmenopausal patients; and a third group, with a very high proliferative activity, includes ER‐ cancers from premenopausal patients. Generally, the amount of estrogen receptors in ER+ cancers is inversely correlated with the proliferative activity. Lower levels of ER in premenopausal in comparison to postmenopausal patients were found in low proliferative activity tumors. Cancer 44:665‐670, 1979.
[Indirect MR-arthrography of the shoulder-value in the detection of SLAP-lesions].

PURPOSE A prospective study to assess the value of indirect magnetic resonance-arthrography (MR-Arthro) in the detection of lesions of the superior labrum (SLAP-lesions). MATERIALS AND METHODS Unenhanced magnetic resonance imaging (MRI) and indirect MR-Arthro of the shoulder were performed in 35 patients (9 females and 26 males) with a history of acute or chronic shoulder disorder. The images of unenhanced MRI and indirect MR-Arthro were analyzed independently from each other for the occurrence of SLAP-lesions and the findings correlated with the arthroscopic results. For arthroscopy, MRI and MR-Arthro, the SLAP-lesions were categorized based on the classification system of Snyder. RESULTS SLAP-lesions were diagnosed by arthroscopy in 22 of 35 patients (63 %). 9 of the 22 lesions (41 %) were classified as type 1, 9 (41 %) as type 2, three (13.5 %) as type 3 and one (4.5 %) as type 4. Using unenhanced MRI sensitivity, specificity and accuracy in the detection of SLAP-lesions were calculated to be 73 %, 85 % and 77 %. Indirect MR-Arthro showed a sensitivity of 91 %, a specificity of 85 % and an accuracy of 89 %. Unenhanced MRI revealed correlation to the arthroscopic classification in 9 of 22 cases (41 %) and indirect MR-Arthro in 18 of 22 cases (82 %). CONCLUSION Indirect MR-Arthro is a non-invasive method which offers excellent sensitivity in the diagnosis of SLAP-lesions. It provides important preoperative informations with regard to the exact location and extent of a tear.