Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of the Receptor Tyrosine Kinase Tie2 in Neoplastic Glial Cells Is Associated with Integrin β1-Dependent Adhesion to the Extracellular Matrix

The abnormal function of tyrosine kinase receptors is a hallmark of malignant gliomas. Tie2 receptor tyrosine kinase is a specific endothelial cell receptor whose function is positively regulated by angiopoietin 1 (Ang1). Recently, Tie2 has also been found in the nonvascular compartment of several tumors, including leukemia as well as breast, gastric, and thyroid cancers. There is, however, little information on the function of the Ang1/Tie2 pathway in the non–stromal cells within human tumors. We found that surgical glioblastoma specimens contained a subpopulation of Tie2+/CD31− and Tie2+/GFAP+ cells, suggesting that Tie2 is indeed expressed outside the vascular compartment of gliomas. Furthermore, analysis of a tissue array consisting of 116 human glioma samples showed that Tie2 expression in the neoplastic glial cells was significantly associated with progression from a lower to higher grade. Importantly, Ang1 stimulation of Tie2+ glioma cells resulted in increased adherence of the cells to collagen I and IV, suggesting that Tie2 regulates glioma cell adhesion to the extracellular matrix. Conversely, the down-regulation of Tie2 levels by small interference RNA or the addition of soluble Tie2 abrogated the Ang1-mediated effect on cell adhesion. In studying the expression of cell adhesion molecules, we found that Tie2 activation was related to the up-regulation of integrin β1 levels and the formation of focal adhesions. These results, together with the reported fact that malignant gliomas express high levels of Ang1, suggest the existence of an autocrine loop in malignant gliomas and that a Tie2-dependent pathway modulates cell–to–extracellular matrix adhesion, providing new insights into the highly infiltrative phenotype of human gliomas. (Mol Cancer Res 2006;4(12):915–26)
Interleukin-17–Dependent Autoimmunity to Collagen Type V in Atherosclerosis

Rationale: Considerable evidence shows atherosclerosis to be a chronic inflammatory disease in which immunity to self-antigens contributes to disease progression. We recently identified the collagen type V [col(V)] &agr;1(V) chain as a key autoantigen driving the Th17-dependent cellular immunity underlying another chronic inflammatory disease, obliterative bronchiolitis. Because specific induction of &agr;1(V) chains has previously been reported in human atheromas, we postulated involvement of col(V) autoimmunity in atherosclerosis. Objective: To determine whether col(V) autoimmunity may be involved in the pathogenesis of atherosclerosis. Methods and Results: Here, we demonstrate Th17-dependent anti-col(V) immunity to be characteristic of atherosclerosis in human coronary artery disease (CAD) patients and in apolipoprotein E–null (ApoE−/−) atherosclerotic mice. Responses were &agr;1(V)-specific in CAD with variable Th1 pathway involvement. In early atherosclerosis in ApoE−/− mice, anti-col(V) immunity was tempered by an interleukin (IL)-10–dependent mechanism. In support of a causal role for col(V) autoimmunity in the pathogenesis of atherosclerosis, col(V) sensitization of ApoE−/− mice on a regular chow diet overcame IL-10–mediated inhibition of col(V) autoimmunity, leading to increased atherosclerotic burden in these mice and local accumulation of IL-17–producing cells, particularly in the col(V)-rich adventitia subjacent to the atheromas. Conclusions: These findings establish col(V) as an autoantigen in human CAD and show col(V) autoimmunity to be a consistent feature in atherosclerosis in humans and mice. Furthermore, data are consistent with a causative role for col(V) in the pathogenesis of atherosclerosis.
Differential Effects of Glycolipid Biosynthesis Inhibitors on Ceramide‐Induced Cell Death in Neuroblastoma Cells

Abstract : An in vitro model of Gaucher's disease in murine neuroblastoma X rat glioma NG108‐15 cells was used to investigate the physiological effects of two specific inhibitors of glucosylceramide synthase, d,l‐threo‐1‐phenyl‐2‐decanoylamino‐3‐morpholino‐1‐propanol (d,l‐PDMP) and N‐butyldeoxynojirimycin (NB‐DNJ), which have been suggested as agents for treatment of glycolipid storage disorders. Incubation of NG108‐15 cells with conduritol‐B‐epoxide, a covalent inhibitor of glucosylce‐ramidase, raised the intracellular concentration of glucosylceramide (GC) by more than fourfold, indicating a glycolipid composition equivalent to that of Gaucher's cells. The level of GC was decreased, and the cells were depleted of gangliosides by postincubation with d,l‐PDMP or NB‐DNJ. Treatment with d,l‐PDMP, but not with NB‐DNJ, resulted in a dose‐dependent reduction of the growth rate and eventually caused cell death in NG108‐15 cells on reaching confluency. An in situ detection assay using terminal nucleotidyltransferase indicated that cell degeneration was accompanied by apoptosis. Lipid analysis by high‐performance TLC revealed that on incubation with d,l‐PDMP, but not with NB‐DNJ, the concentration of endogenous ceramide was elevated by threefold. Ceramide elevation and apoptosis were also observed when NG108‐15 cells were incubated with daunorubicin, which was previously reported to induce programmed cell death by stimulation of ceramide synthesis. Structural characterization by HPLC and subsequent laser desorption mass spectrometry revealed that the endogenous ceramide contained fatty acids with chain lengths ranging from C14 : 0 to C24 : 0. The results indicate that elevation of levels of these ceramide species by incubation with d,l‐PDMP or daunorubicin induces programmed cell death in NG108‐15 cells. Because ceramide accumulation and cell death were not observed on incubation with NB‐DNJ, its use is suggested to be less toxic than that of d,l‐PDMP for treatment of Gaucher's disease and other sphingolipid storage disorders.
Analysis of immunocytochemical and molecular BRAF expression in thyroid carcinomas: A cytohistologic institutional experience

It has been generally demonstrated that the valine‐to‐glutamic acid substitution at position 600 (V600E) in the v‐Raf murine sarcoma viral oncogene homolog B1 (BRAF) gene is an effective diagnostic/prognostic marker mainly for papillary thyroid carcinoma (PTC). The detection of this mutation typically has been achieved using DNA‐based techniques. The recently introduced monoclonal V600E antibody (clone VE1) is likely to be an alternative strategy for detecting this mutation in thyroid lesions. The authors investigated molecular and immunocytohistochemical BRAF analyses in a prospective series of samples from patients with PTC.
Activation of Hemoglobin C Synthesis in Sheep Marrow Culture

Erythropoietin preferentially stimulates hemoglobin C synthesis in suspension cultures of marrow cells from sheep homozygous for hemoglobin A; the amount of synthesis is dependent on the dose of erythropoietin and is blocked by antiserum to erythropoietin. The results provide the first in vitro evidence that erythropoietin mediates the hemoglobin A → C "switch" in sheep and indicate that bone marrow cultures may be used to investigate the mechanisms involved in the preferential gene activation characteristic of the hemoglobin A → C system.
An in vitro study of anterior cruciate ligament strain induced by quadriceps and hamstrings forces

Strain in the anteromedial fibers of the anterior cruciate ligament [ACL(am)] was studied in six cadaver knees. ACL(am) strain was measured in five knees during the application of isometric quadriceps forces alone and simultaneously applied isometric quadriceps and hamstrings forces at 10° increments from 0° to 90° of knee flexion. ACL(am) strain during muscle loading was measured with respect to the ACL(am) strain measured with the knee in its resting position (neutral or near neutral position). A sixth knee was used to investigate the reproducibility of the resting position and quadriceps‐induced ACL(am) strains. The strains induced in the ACL(am) by the quadriceps were significantly greater than 0 at knee flexion angles from 0 to 40° and not significantly different from 0 for 50 to 90° The ACL(am) strains induced by simultaneously applied hamstrings and quadriceps forces were not significantly different from 0 at any of the knee flexion angles tested. Simultaneously applied hamstrings and quadriceps forces significantly reduced ACL(am) strain at 10, 20, and 90° of knee flexion compared to the ACL(am) strain induced by quadriceps forces alone. The hamstrings are potentially capable of both significantly reducing and negating quadriceps‐induced ACL(am) strain at 10 and 20° of knee flexion.
Intracellular growth of Afipia felis, a putative etiologic agent of cat scratch disease

The organism Afipia felis, which is though to be an etiologic agent of cat scratch disease, is a gram-negative rod that is clearly seen in infected tissue but is very difficult to isolate from clinical specimens; there has been only one report to date of the successful isolation and maintenance of the bacterium on artificial medium. We have found that A. felis will attach, invade via phagocytosis, and multiply intracellularly within the phagosomes of primary human monocytes and HeLa cells. Once in the cell, the bacterium appears to change morphologically, becoming longer and more pleomorphic, and loses its ability to grow on an artificial medium. Unique proteins have been identified in both the intra- and extracellular variants of A. felis. Convalescent-phase sera from patients with cat scratch disease react poorly with intracellular and extracellular bacteria, suggesting a poor humoral response. The tissue culture protocol presented has been used to isolate 14 new strains of A. felis and has for the first time permitted study of the pathogenesis of this unique organism.
Application of a multiplex pbp2b and pbp2x PCR for prediction of penicillin resistance in Streptococcus pneumoniae.

Sir, In Streptococcus pneumoniae, penicillin binding proteins (PBPs) 2b and 2x are the primary targets for penicillin. Hence, they are the first PBPs to be altered following mutations that lead to the development of penicillin resistance. Within the transpeptidase-encoding regions of the pbp2b and pbp2x genes, a few specific nucleotide changes have been shown to be common to penicillin-resistant pneumococci from many parts of the world. Polymerase chain reaction (PCR) primers have been developed to specifically amplify these mutant alleles. The primers are designed to be complementary to the mutant sequence, such that a PCR product is only produced if the mutation is present in the gene. 1,2 However, these previously developed PCR assays are limited to only detecting mutations in one of the pbp genes, and/or they require two or more separate PCR reactions to accommodate tests for all the resistance alleles. In this study, we report the evaluation of a one-tube, multiplex PCR reaction for detection of pbp2b and pbp2x mutations associated with penicillin resistance in S. pneumoniae. The primers used in the reaction are R1 to R4, P5 and P6, specific for pbp2b, and Pn-RX1 and Pn-RX2 for pbp2x. The sequences of these primers have been reported previously. 2,3 Possible PCR products have sizes (in bp) of 183 (primer pair Pn-RX1 and Pn-RX2), 214 (primer pair R4 and P6), 328 (primer pair R2 and P6), 331 (primer pair R1 and P6), 334 (primer pair R3 and P6) and 682 (primer pair P5 and P6—used as a PCR control). To test the multiplex PCR assay, a collection of 383 nasopharyngeal isolates of S. pneumoniae4 obtained from among 1978 children aged less than 6 years attending 79 day care centres and kindergartens in all areas of Hong Kong was tested. The penicillin MICs of the isolates were determined by the Etest method. The 40 µL optimal PCR reaction comprised 2.2 mM MgCl2, dNTP at 200 µM, 1 U of AmpliTaq Gold in 1× PCR buffer (Applied Biosystems, Foster City, CA, USA), primers (P5 and P6 at 1 µM; R1 to R4 at 0.1 µM; PnRx1 and PnRx2 at 0.2 µM) and 4 µL of DNA template (generated by rapid alkaline lysis of cells). PCR was carried out using the following conditions: an initial activation at 95°C for 8 min, then 10 cycles of
Mindful Parenting Decreases Aggression and Increases Social Behavior in Children With Developmental Disabilities

Research shows that after training in the philosophy and practice of mindfulness, parents can mindfully attend to the challenging behaviors of their children with autism. Parents also report an increased satisfaction with their parenting skills and social interactions with their children. These findings were replicated and extended with 4 parents of children who had developmental disabilities, exhibited aggressive behavior, and had limited social skills. After mindfulness training, the parents were able to decrease aggressive behavior and increase their children's social skills. They also reported a greater practice of mindfulness, increased satisfaction with their parenting, more social interactions with their children, and lower parenting stress. Furthermore, the children showed increased positive and decreased negative social interactions with their siblings. We speculate that mindfulness produces transformational change in the parents that is reflected in enhanced positive behavioral transactions with their children.
The CHL 1 (CTF 1) gene product of Saccharomyces cerevisiae is important for chromosome transmission and normal cell cycle progression in G2/M.

We have analyzed the CTF1 gene, identified in a screen for mutants with decreased chromosome transmission fidelity and shown to correspond to the previously identified chl1 mutation. Chl1 null mutants exhibited a 200‐fold increase in the rate of chromosome III missegregation per cell division, and near wild‐type rates of marker homozygosis on this chromosome by mitotic recombination. Analysis of the segregation of a marker chromosome indicated that sister chromatid loss (1:0 segregation) and sister chromatid non‐disjunction (2:0 segregation) contributed equally to chromosome missegregation. A genomic clone of CHL1 was isolated and used to map its physical position on chromosome XVI. Nucleotide sequence analysis of CHL1 revealed a 2.6 kb open reading frame with a 99 kd predicted protein sequence that contained two PEST sequences and was 23% identical to the coding region of a nucleotide excision repair gene, RAD3. Domains of homology between these two predicted protein sequences included a helix‐turn‐helix motif and an ATP binding site containing a helicase consensus. Mutants lacking the CHL1 gene product are viable and display two striking, and perhaps interrelated, phenotypes: extreme chromosome instability and a delay in cell cycle progression in G2/M. This delay is independent of the cell cycle checkpoint that requires the function of the RAD9 gene.
Regional Adipose Tissue Metabolism in Postmenopausal Women After Treatment with Exogenous Sex Steroids

In order to evaluate the effect of exogenous sex steroids on adipose tissue metabolism, two groups of postmenopausal women were studied. In one of the groups, the effect of 50 micrograms ethinyl estradiol (EE) was investigated given orally alone and in combination with 10 mg norethisterone acetate (NET). This combination is reminiscent of an old high dose oral contraceptive. In the other group, the effect of 3 mg 17 beta-estradiol was evaluated when administered percutaneously alone and in combination with 300 mg micronized progesterone given orally. These substances and doses were chosen to provide a "physiological" hormonal influence. In the femoral region 50 micrograms EE induced an increase in LPL activity. This elevated LPL value was reversed with the addition of 10 mg NET. Moreover, during treatment with 50 micrograms EE, a decrease in norepinephrine stimulated lipolysis was seen in the abdominal region. The percutaneous administration of 17 beta-estradiol with or without micronized progesterone, however, was inert as regards subcutaneous adipose tissue metabolism. Our findings indicate, therefore, that EE in doses used in oral contraception might promote lipid accumulation in the femoral adipose tissue depot.
Is Total Parathyroidectomy the Treatment of Choice for Hyperparathyroidism in Multiple Endocrine Neoplasia Type 1?

Objective:The aim of the present report is to describe the results obtained with total parathyroidectomy (TPTX) guided by rapid intraoperative parathyroid hormone (PTH) evaluation, followed by immediate parathyroid autograft with fresh tissue. Summary Background Data:Surgery for hyperparathyroidism (HPT) in multiple endocrine neoplasia type 1 (MEN1) is performed with various surgical approaches. Methods:We report our 16-year experience of surgical treatment of 51 MEN1-HPT patients using TPTX and thymectomy. Forty-five patients underwent TPTX as the first surgical procedure, whereas for 6 patients, a parathyroid operation was the second surgical procedure. PTH intraoperative values less than 10 pg/mL, at the end of the surgery, were indicative for reimplantation of a few fragments (∼7) of fresh parathyroid tissue in the brachioradial muscle of the forearm. Parathyroid autograft was performed in all patients, except 3 in whom the fourth parathyroid gland was not found. Results:Persistent hypoparathyroidism occurred in 13 patients (25%), with higher incidence in patients undergoing a second surgical revision for cervical recurrence than in patients submitted to the first surgery. At follow-up, 5 recurrences (∼10%) in the forearm were observed after a mean time of 7 ± 5 (M ± SD) years. No cervical recurrence was documented. The forearm recurrence was treated with removal of 1 or 2 enlarged fragments obtaining the resolution of HPT in all but 1 case. Conclusions:Based on the occurrence of complications in our experience, TPTX followed by autograft and guided by intraoperative PTH monitoring represents a better surgical option in MEN1-HPT compared with other surgical approaches.
Caffeine intake is not associated with serum testosterone levels in adult men: cross-sectional findings from the NHANES 1999–2004 and 2011–2012

Abstract Objective: The association of caffeine intake with testosterone remains unclear. We evaluated the association of caffeine intake with serum testosterone among American men and determined whether this association varied by race/ethnicity and measurements of adiposity. Methods: Data were analyzed for 2581 men (≥20 years old) who participated in the cycles of the NHANES 1999–2004 and 2011–2012, a cross-sectional study. Testosterone (ng/mL) was measured by immunoassay among men who participated in the morning examination session. We analyzed 24-h dietary recall data to estimate caffeine intake (mg/day). Multivariable weighted linear regression models were conducted. Results: We identified no linear relationship between caffeine intake and testosterone levels in the total population, but there was a non-linear association (pnonlinearity < .01). Similarly, stratified analysis showed nonlinear associations among Mexican-American and Non-Hispanic White men (pnonlinearity ≤ .03 both) and only among men with waist circumference <102 cm and body mass index <25 kg/m2 (pnonlinearity < .01, both). Conclusion: No linear association was identified between levels of caffeine intake and testosterone in US men, but we observed a non-linear association, including among racial/ethnic groups and measurements of adiposity in this cross-sectional study. These associations are warranted to be investigated in larger prospective studies.
Anatomical description of the facet joint innervation and its implication in the treatment of recurrent back pain.

AIM Many techniques are used in the back pain treatment, standing out the facet denervation as a therapeutic option for pain that originates in the facet joints. It's known that the facet joint is an abundant area of nocireceptor innervation, although the distribution and the location of the involved branches have not being well demonstrated. A good comprehension about the affected innervation is very important to get an effective treatment. Purpose of study was to describe innervation of the lumbar facet joints, potentially used in the diagnosis and treatment of painful pictures of the lumbar region by facet syndrome. STUDY DESIGN anatomical study of nerve roots distribution of the facet joint 3 human corpses. The determination of the neurotomy s point was carried out by direct visualization and the radiological study in human parts. METHODS Three anatomical pieces of the human lumbar spine were dissected. In those 3 pieces, the facet joint innervation distribution was studied thoroughly using surgical microscope and microsurgical technique. In one of the pieces the needles positioning was first made to test through the radiological study the possible application of the precise denervation in low back pain treatment. RESULTS The L1 to L4 segments, each dorsal branch of root emits a medial branch that emerges from intertransversal ligament. This branch crosses the superior margin of the medial termination of transverse process, passing through the root of the superior articulate process. Each branch innerves the anterior region of the inferior facet and the inferior portion of articulation which one spins around. The L5 dorsal branch was larger than the superior branches. It emerges dorsally and in the inferior region on top of the sacrum wing. This nerve is in the bone fissure of the junction between the wing and the posterior region of the sacrum articular process. Near the inferior portion of the articular process, the nerve ramifies itself in lateral and medial branch. The medial branch comes back around the inferior portion of the lumbar-sacrum articulation that it innervates. CONCLUSIONS We didn't note great variations in the anatomy from L1 do L4. The L5 segment has a different distribution of the branches that should be considered when we do a percutaneous denervation procedure. The approach of the needle must touch the transverse process and feels the resistance of the articular joint . The determination of the neurotomy s point tends to become more precise denervation procedure.
The need for a patient-tailored Helicobacter pylori eradication protocol prior to bariatric surgery

Objective High-quality data indicating the advantages of preoperative Helicobacter pylori screening and eradication as well the clinical outcomes of patients with and without H. pylori after bariatric surgery are lacking. Methods In total, 96 morbidly obese patients with H. pylori preparing for bariatric surgery were retrospectively reviewed. Results Of 96 biopsy specimens, 73 (76%) were positive for H. pylori on initial Giemsa staining. These patients were treated with the standard 7-day antibiotic treatment protocol corrected by the individual patient’s creatinine clearance rate and body mass index and received a 30% higher dose because of their H. pylori positivity. A linear correlation was found between the effective antibiotic dose and the BMI with a recurrence rate of only 2.1% (2/96 patients). The preoperative percent estimated weight loss before surgery (17%) and in the first year of follow-up (68%–88%) was statistically equal between H. pylori-positive and -negative patients. Two early postoperative infectious complications and two postoperative surgical complications occurred in the preoperatively H. pylori-positive patients. Conclusions A patient-tailored H. pylori eradication protocol prior to bariatric surgery is mandatory to improve the eradication rate and reduce the incidence of postoperative complications in mostly asymptomatic H. pylori-positive bariatric candidates.