Gastrointestinal autonomic nerve tumors. A clinicopathological, immunohistochemical, and ultrastructural study of 12 cases

The gastrointestinal autonomic nerve tumor (GAN tumor) is an uncommon stromal tumor of the intestinal tract and retroperitoneum first described by Herrera and associates in 1984. Distinction of GAN tumors from other gastrointestinal stromal tumors is based on electron microscopic findings. Thus far there have been 12 reported cases. We present an additional 12 GAN tumors, identified by us during 4 years. There were seven male and five female patients and they ranged in age from 10 to 85 years (mean: 58 years). Sites of the tumors were stomach (three), jejunum (two), ileum (four), mesentery (one), and retroperitoneum (two). Eight of the tumors measured > 10 cm in greatest dimension. Usually well circumscribed, the neoplasms were tan to light pink, sometimes hemorrhagic, and soft. There was a variety of histologic patterns including fascicles, palisades, and whorls. Mitotic activity varied from 0 to 23 mitosis per 10 high-power fields (HPF). Using a panel of 10 immunohistochemical stains, only vimentin was consistently positive. There was neuron-specific enolase reactivity in six and S-100 protein reactivity in two cases. All muscle markers were negative. Ultrastructural studies showed neuron-like cells with long axonic cytoplasmic processes ending in bulbous synapse-like structures containing dense-core neurosecretory granules and clear vesicles. Basement membrane was absent. These features are reminiscent of ganglia of the intestinal autonomic nervous system. The patients were followed for 5-125 months (mean of 26 months). Tumor recurred or metastasized to the liver in seven patients (58%) and four patients died with tumor. There were correlations between tumor size (> 10 cm), mitotic count (at least five per 10 HPF), and aggressive behavior.     

The effect of unilateral destruction of the head of the caudate nucleus with kainic acid on the structure of the wakefulness-sleep cycle and the EEG in rats

The wakefulness-sleep cycle characteristics changes in Wistar line rats after unilateral lesions of the neuronal elements of the caudate nucleus head with kainic acid (at sparing the conducting ways going through this structure) were studied. It was shown that in 4 days after acid injection the share of the active wakefulness and light slow-wave sleep is significantly increased, whereas the percentage of the passive wakefulness, deep slow-wave stage, and paradoxal sleep (up to 80%) is reduced. The wakefulness-sleep cycle in rats is completely normalized on the 7th day after injection. The obtained data allow to consider the caudate nucleus as a modulator for wakefulness-sleep cycle, that is the structure involved in the motive activity regulation.     

Influence of receptor number on the stimulation by salmeterol of gene transcription in CHO-K1 cells transfected with the human beta2-adrenoceptor

We investigated the behavior of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APx), in potato tubers during storage at low temperature. SOD activity increased temporarily within 3 weeks and was higher at 1 degree C than at 20 degrees C. APx activity also increased more at low (1 degree C) than at higher temperatures (5 and 20 degrees C). The contents of ascorbic acid (AsA), which is the substrate of APx, decreased immediately within 3 weeks and then gradually decreased until 15 weeks. The activity of CAT, the other enzyme which can scavenge hydrogen peroxide, decreased once in the first six weeks and thereafter increased to 15 weeks. Thus, the enhancement of the active oxygen-scavenging system that was induced by low temperature in potato tubers could result not only in a decrease of AsA but also in combined increases in APx and CAT activity whose manners were different.     

Identification of a novel inhibitor (NSC 665564) of dihydroorotate dehydrogenase with a potency equivalent to brequinar

A novel inhibitor of dihydroorotate dehydrogenase (DHO-DH) has been discovered using data from the National Cancer Institute's in vitro drug screen. Upon analysis of cytotoxicity results from the sixty tumor cell lines used in this screen, the COMPARE program predicted that NSC 665564 was likely to have the same mechanism of inhibition as brequinar, a known potent inhibitor of DHO-DH. We validated this prediction experimentally using MOLT-4 lymphoblast and found the IC50 of brequinar (0.5 microM) and NSC 665564 (0.3 microM) were comparable and that this induced cytotoxicity was reversed by either uridine or cytidine. The enzyme target of NSC 665564 was shown to be identical to that of brequinar when incubation with each drug followed by a 1 h pulse with [14C] sodium bicarbonate resulted in cellular accumulation of [14C]N-carbamyl-L-aspartic acid and [14C]L-dihydroorotic acid, with concurrent marked depletion of CTP and UTP. The Ki's for NSC 665564 and brequinar were 0.14 and 0.24 microM, respectively, when partially purified MOLT-4 mitochondria (the site of DHO-DH) were used. These results show that mechanistic predictions obtained using correlations from the COMPARE algorithm are independent of structure since the structure of NSC 665564 is dissimilar to that of other established DHO-DH inhibitors.     

Screening for diabetic retinopathy: the utility of nonmydriatic retinal photography in Egyptian adults

BACKGROUND AND OBJECTIVE: Drug resistance has become a major cause of treatment failure in patients with acute leukemia. P-glycoprotein (Pgp), which is associated with the multidrug resistance (MDR) phenotype, has been reported to be an important predictor of treatment outcome. The aim of this study was to analyze the value of Pgp expression in bone marrow or peripheral blood as a predictor of the response to remission induction chemotherapy as well as the duration of remission in patients with de novo acute myeloid leukemia (AML). DESIGN AND METHODS: We examined the expression of Pgp in 82 patients with de novo AML using an immunocytochemical assay with the C219 monoclonal antibody. RESULTS: Twenty-seven of the 82 patients (33%) were C219-positive in from 1% to 100% of their cells. Thirteen cases (16%) showed a positive reaction in more than 50% of the leukemic cells. Only hyperleukocytosis was significantly associated with higher expression of Pgp. Although 8 of the 13 cases (62%) with more than 50% of cells having Pgp expression were CD34-positive, this association was not statistically significant. A univariate analysis of resistance to induction therapy showed a significantly higher resistance rate in patients with increased Pgp expression (P = 0.01) as well as in those patients with decreased reactivity to myeloperoxidase. The multivariate analysis revealed the independent prognostic value of Pgp expression. C219 reactivity did not have an influence on remission duration. INTERPRETATION AND CONCLUSIONS: Our data indicate that P-glycoprotein expression is a reliable marker of resistance to induction treatment in patients with de novo AML.     

Mechanical analysis of hollow fiber membrane integrity in water reuse applications

In order to gain insight into membrane fiber failure (i.e., loss of integrity), properties of five hollow fiber membranes and four hollow fiber modules were evaluated. Specifically, membrane material, membrane symmetry, fiber modulus of elasticity, fiber diameter and thickness, module potting technique, module flow pattern (inside-out or outside-in), and coliform breakthrough were investigated. The approach combined evaluation of the above properties with mathematical modeling of structure-fluid interactions to comprehensively evaluate the properties most important for maintaining hollow fiber membrane integrity. Tensile strength testing revealed that the strongest fiber was an asymmetric polyacrylonitrile membrane fiber. The weakest fiber was a symmetric polyethylene membrane fiber. Pilot plant testing on the four membrane modules revealed that membrane symmetry may be a more important factor than potting technique for hollow fiber integrity. Results from the SEM and tensile testing were used as input to a finite element analysis model used to evaluate time-dependent structure-fluid interactions. It was found that additional stresses at the juncture of the potting material and the hollow fiber membranes exist. These stresses likely lead to the formation of fractures.     

A performance evaluation of three membrane bioreactor systems: aerobic, anaerobic, and attached-growth

Water sustainability is essential for meeting human needs for drinking water and sanitation in both developing and developed countries. Reuse, decentralization, and low energy consumption are key objectives to achieve sustainability in wastewater treatment. Consideration of these objectives has led to the development of new and tailored technologies in order to balance societal needs with the protection of natural systems. Membrane bioreactors (MBRs) are one such technology. In this investigation, a comparison of MBR performance is presented. Laboratory-scale submerged aerobic MBR (AMBR), anaerobic MBR (AnMBR), and attached-growth aerobic MBR (AtMBR) systems were evaluated for treating domestic wastewater under the same operating conditions. Long-term chemical oxygen demand (COD) and total organic carbon (TOC) monitoring showed greater than 80% removal in the three systems. The AnMBR system required three months of acclimation prior to steady operation, compared to one month for the aerobic systems. The AnMBR system exhibited a constant mixed liquor suspended solids concentration at an infinite solids retention time (i.e. no solids wasting), while the aerobic MBR systems produced approximately 0.25 g of biomass per gram of COD removed. This suggests a more economical solids management associated with the AnMBR system. Critical flux experiments were performed to evaluate fouling potential of the MBR systems. Results showed similar critical flux values between the AMBR and the AnMBR systems, while the AtMBR system showed relatively higher critical flux value. This result suggests a positive role of the attached-growth media in controlling membrane fouling in MBR systems.     

Prosthetic valve endocarditis: superiority of surgical valve replacement versus medical therapy only

The objective of our study was to assess the long-term outcome of patients with prosthetic valve endocarditis. We used a multicenter, prospective, observational study design. Six university teaching hospitals with high volume cardiothoracic surgery participated. Seventy-four patients with prosthetic valve endocarditis as defined by explicit, objective criteria were selected for participation. All patients were followed up prospectively for 1 year. Thirty-one percent and 69% had development of endocarditis within 60 days of valve insertion ("early") and after 60 days ("late"), respectively. The most common causes were Staphylococcus epidermidis (40%), Staphylococcus aureus (20%), streptococcal species (18%), and aerobic gram-negative bacilli (11%). Physical signs of endocarditis (new or changing murmur, stigmata, emboli) were seen in 58%. At 6 months and 12 months, mortality was 46% and 47%, respectively. Surgical replacement of the infected valve led to significantly lower mortality (23%) as compared with medical therapy alone (56%), as assessed by both univariate and multivariate analyses (p < 0.05). Improved outcome was seen for the surgical group even when controlling for severity of illness at time of diagnosis. From these findings we conclude that accurate assessment of outcome in prosthetic valve endocarditis requires long-term follow-up of at least 6 months following diagnosis. Surgical therapy warrants greater scrutiny; evaluation in controlled clinical trials is appropriate.