The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells

To assess the efficiency of nasally administered cartilage-specific collagens as vaccination against development of arthritis and to ameliorate already established chronic arthritis, experimental models which develop chronic arthritis, pristane-induced arthritis (PIA), and homologous collagen-induced arthritis (CIA) in the rat were selected. Cartilage-specific collagens type IX (CIX) and type II (CII) were used for vaccination intranasally. A single dose of 250 microg CII instilled intranasally in rats with established PIA ameliorated the disease. For the prevention of disease, the same dose given before immunization was found to be most effective. Most importantly, the disease was more severe if this dose was given three times. For treatment of PIA, CIX was found to be more effective than CII, whereas for treatment of CIA only CII was effective. The amelioration of CIA was associated with a marked suppression of delayed type hypersensitivity and the flare reaction to CII and lower levels of IgG2b anti-CII antibodies in serum, i.e., with suppression of the TH1 rather than the TH2 response to CII. These findings, that cartilage proteins, if given intranasally, can both prevent and ameliorate established chronic arthritis in rats, are of significant importance for possible use in rheumatoid arthritis. The identification of two different cartilage-specific proteins (CII and CIX) effective against a disease induced with a well-defined nonimmunogenic adjuvant such as pristane will be of value for enhancing the effectiveness of the treatment.     

Role of the endothelium in placental dysfunction after fetal cardiac bypass

BACKGROUND: Fetal cardiac bypass causes placental dysfunction, characterized by increased placental vascular resistance, decreased placental blood flow, hypoxia, and acidosis. Vasoactive factors produced by the vascular endothelium, such as nitric oxide and endothelin 1, are important regulators of placental vascular tone and may contribute to this placental dysfunction. METHODS: To investigate the role of the vascular endothelium in placental dysfunction related to fetal cardiac bypass, we studied 3 groups of fetal sheep. In the first group (n = 7) we determined placental hemodynamic responses before and after bypass to an endothelium-dependent vasodilator (acetylcholine), an endothelium-independent vasodilator (nitroprusside), and endothelin 1. In the second group (n = 8) a nonspecific endothelin receptor blocker (PD 145065) was administered and placental hemodynamic values were measured before and after bypass. In the third group (n = 5) endothelin 1 levels were measured before and after bypass. RESULTS: Before fetal cardiac bypass exogenous endothelin 1 decreased placental blood flow by 9% and increased placental resistance by 9%. After bypass endothelin 1 decreased placental flow by 47% and increased resistance by 106%. There was also a significant attenuation of the placental vascular relaxation response to acetylcholine after bypass, whereas the response to nitroprusside was not significantly altered. In fetuses that received the PD 145065, placental vascular resistance increased significantly less than in control fetuses (28% versus 62%). Similarly, placental blood flow decreased significantly more (from 6. 3 +/- 3.1 to 28.3 +/- 10.4 pg/mL; P =.01) in control fetuses than in fetuses receiving PD 145065 (33% versus 20%). Umbilical venous endothelin 1 levels increased significantly in fetuses exposed to fetal bypass but did not change in control fetuses. CONCLUSIONS: The basal endothelial regulatory mechanisms of placental vascular tone were deranged after fetal cardiac bypass. Endothelin receptor blockade, which substantially reduced postbypass placental dysfunction, and other interventions aimed at preserving endothelial function may be effective means of optimizing fetal outcome after cardiac bypass.     

Adult psychological functioning of individuals born with craniofacial anomalies

This study represents an initial investigation into the adult psychological functioning of individuals born with craniofacial disfigurement. A total of 24 men and women born with a craniofacial anomaly completed paper and pencil measures of body image dissatisfaction, self-esteem, quality of life, and experiences of discrimination. An age- and gender-matched control group of 24 non-facially disfigured adults also completed the measures. As expected, craniofacially disfigured adults reported greater dissatisfaction with their facial appearance than did the control group. Craniofacially disfigured adults also reported significantly lower levels of self-esteem and quality of life. Dissatisfaction with facial appearance, self-esteem, and quality of life were related to self-ratings of physical attractiveness. More than one-third of craniofacially disfigured adults (38 percent) reported experiences of discrimination in employment or social settings. Among disfigured adults, psychological functioning was not related to number of surgeries, although the degree of residual facial deformity was related to increased dissatisfaction with facial appearance and greater experiences of discrimination. Results suggest that adults who were born with craniofacial disfigurement, as compared with non-facially disfigured adults, experience greater dissatisfaction with facial appearance and lower self-esteem and quality of life; however, these experiences do not seem to be universal.     

Frit salvage innovation of cathode ray tube by initiating to crack along the seal edge

This article describes a thermal stress boundary element analysis which was carried out to select a mechanical device that would innovate the frit salvage of cathode ray tubes (CRT). The panel and funnel of a CRT are fritted at the seal edge. To reuse a CRT, the panel and funnel are separated by etching and then applied a thermal shock. This procedure is known as frit salvage. Current yield of the frit salvage success rate is about 61 %, which means that 39% of the components are lost and cannot be reused. The financial burden can be reduced if the salvage rate is improved through a better understanding of the thermal shock mechanism.

During thermal shock, a crack was observed to initiate at the end of the axes and traverses towards the corner along the seal end. A CRT is lost when the crack travels along the diagonal corner. A thermal stress analysis was carried out using the boundary element method. The analysis determined that maximum stresses are located near the blend radius on the panel skirt at approximately 1–2 inches on either side of the diagonal. Also it was found that the stresses along the frit seal edge are uniform from the end of the major and minor axes towards the diagonal. The stresses at the diagonal location were reduced by approximately 29%. The direction and location of the crack obtained by the boundary element anlysis were consistent with those observed in the frit salvage procedure.

The crack's promoter along the seal edge is used to protect thermal shock on the outer face panel near the heel radius in order to prevent thermal failure on the diagonal corner. The resultant stresses' directions through the crack's promoter have two holds. The directions of the dominant high stresses at the seal edge through the crack's promoter were changed perpendicular to the seal edge. Therefore, it induces the crack to follow along the seal edge. Secondly, the stresses' directions on a diagonal corner have also been changed to be perpendicular to the seal edge. Consequently, this will prevent the crack along the seal edge from propagating to the diagonal corner, as the crack will advance normally to the maximum principal stress. The crack continues to traverse along the dominant high stress lines at the seal edge as required for a successful frit salvage process. This application is an excellent example of the advantages of using the boundary element method in an industrial setting.     

Intraoperative recording of the bulbocavernosus reflex

OBJECTIVE: To demonstrate the feasibility of intraoperative monitoring of the bulbocavernosus reflex (BCR) as an indicator of the functional integrity of sacral nervous structures to aid in preventing their intraoperative injury. METHODS: Intraoperative BCR was elicited by electrical stimulation of the dorsal penile/clitoral nerve in 119 patients anesthetized with propofol, fentanyl, and nitrous oxide, with short-acting relaxant. Thirty-eight patients underwent surgery without risk, whereas 81 underwent surgery with risk of damage to sacral structures. Different patterns of stimuli were applied through silver/silver chloride disc electrodes placed on the dorsal aspect of the penis in males and over the clitoris (cathode) and adjacent labia (anode) in females. Recordings were made from the anal sphincter using intramuscular wire electrodes introduced within a 27.5 gauge needle, with two electrodes each inserted in the right and left hemisphincter muscles. Preoperatively, some patients had minor urinary problems in controlling their sphincters. RESULTS: The BCR was reliably recorded without habituation under this anesthetic regime. Optimal stimulating parameters were found to be double pulses (0.5-ms duration), with an interstimulus interval of 3 ms, stimulating rate of 2.3 Hz, and intensity of 20 mA. With these parameters, it was possible to record the BCR intraoperatively in all patients. Isoflurane and nitrous oxide significantly suppressed the BCR, and muscle relaxant completely abolished it. CONCLUSION: We demonstrated that it is feasible, under certain anesthetic regimes, to intraoperatively monitor the BCR in both children and adults (24 d to 74 yr of age) who did not have significantly affected function in sacral nervous structures.     

The progression of untreated lumbar kyphosis and the compensatory thoracic lordosis in myelomeningocele

Radiographs of 37 patients with untreated lumbar kyphosis without congenital vertebral anomalies associated with myelomeningocele were analyzed. With an average interval between radiographs of 6.2 years, the kyphosis was noted to increase at a mean rate of 4.3 degrees per year without correlation to its initial magnitude. The compensatory lordosis was more variable and progressed at a mean of 2.5 degrees per year. Children under the age of 2 years were more likely to increase the Cobb angle and the height of their kyphosis. There was an inverse relationship between the height of the kyphus and the lumbar spine height and the resultant growth of each. A modified kyphotic index less than 4 correlated with an increase in the curve and height of the kyphosis and the subsequent desire for surgery. Wide variability in radiographic parameters make predictions for an individual patient difficult.     

Coexpression of Bcl-2, c-Myc, and p53 oncoproteins as prognostic discriminants in patients with colorectal carcinoma

Lanepitant is a high-affinity, selective neurokinin-1 receptor (NK-1) and is effective in the dural inflammation model of acute migraine. Lanepitant 30, 80, and 240 mg given orally was evaluated in a double-blind, placebo-controlled crossover study to determine its effect in reducing migraine pain and severity of associated symptoms. Outpatients treated four migraine headaches of moderate or severe pain intensity with study drug according to a randomization schedule. They recorded their pain intensity and severity of migraine-associated symptoms at 30, 60, 90, and 120 min. Although 53 patients were randomly allocated to a treatment sequence, only 40 patients completed all treatments. There was no statistically significant difference in improvement in migraine pain at any time for any of the treatments. Additionally, there was no change in severity of migraine-associated symptoms associated with lanepitant therapy. No adverse events could be attributed to lanepitant. Lanepitant was ineffective orally in treating acute migraine in this trial. This may be due to poor bioavailability during a migraine attack. Alternatively, the neurogenic inflammation hypothesis may not apply to migraine.     

Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction

Fas ligand is believed to mediate immune privilege in a variety of tissues, including the eye, testis, and a subset of tumors. We tested whether expression of Fas ligand on pancreatic islets either following adenoviral or germline gene transfer could confer immune privilege after transplantation. Islets were infected with an adenoviral vector containing the murine Fas ligand cDNA (AdFasL), and were transplanted into allogenic diabetic hosts. Paradoxically, AdFasL-infected islets underwent accelerated neutrophilic rejection. The rejection was T cell and B cell independent and required Fas protein expression by host cells, but not on islets. Similarly, transgenic mice expressing Fas ligand in pancreatic beta cells developed massive neutrophilic infiltrates and diabetes at a young age. Thus, Fas ligand expression on pancreatic islets results in neutrophilic infiltration and islet destruction. These results have important implications for the development of Fas ligand-based immunotherapies.