Subdiaphragmatic and intrathoracic paraspinal malignant peripheral nerve sheath tumors: a clinicopathologic study of 25 patients and 26 tumors

BACKGROUND: To determine the effects of anatomic site on the presentation and diagnosis of malignant peripheral nerve sheath tumors (MPNSTs) and on the treatment and outcomes of the patients, the authors initiated a study of these tumors at different sites. An earlier report described MPNSTs of the buttock and lower extremity, and the current series analyzes those presenting at intrathoracic (IT) and subdiaphragmatic (SD) paraspinal sites. METHODS: The authors reviewed data on patients with paraspinal MPNSTs who were seen at Memorial Hospital during the period 1960-1995 and for whom histologic slides were available. Various clinicopathologic parameters and their effects on patient outcomes were examined. RESULTS: Twenty-five patients with 26 tumors were evaluated. Seven tumors were IT and 19 were SD; 60% of the patients had neurofibromatosis type 1 (NF1). Most patients presented with pain, and a diagnostic delay (of 3 months to 2 years) was often noted. Mean tumor sizes for SD and IT tumors were 14.3 cm and 6.6 cm, respectively. Most MPNSTs were composed of spindle cells in fascicles. Twenty-seven percent exhibited divergent differentiation. Twenty-four tumors were high grade, and a low grade component was identified in 8 tumors. Surgical resection was attempted for 23 tumors (88%), but complete resection was achieved in only 6 cases (23%). Eighty percent of the patients died of their tumors, 2-year and 5-year survival rates were 35% and 16%, and median survival was 8.5 months. Significant prognostic factors were tumor size <5 cm, the presence of a low grade component, and complete tumor resection. CONCLUSIONS: Paraspinal MPNSTs have more aggressive behavior than peripherally located tumors, mainly because of the difficulty encountered in resecting them completely. Prognoses of patients with MPNST at this site appear to be affected by resection status, tumor size, and tumor grade.     

Response of two populations of holm oak (Quercus rotundifolia Lam.) to sulfur dioxide

Experiments were carried out with seedlings of Quercus rotundifolia Lam., an evergreen schlerophyllous tree typical of the Spanish Mediterranean climate environments. Fruits were collected in two distant (800 km) populations located in the center (southern Spain) and northern border (northern Spain) of the area of distribution of the species. One-month-old potted plants were grown for 130 days in an enriched atmosphere of SO2 (0.23 ppm, 14 h/day) in controlled (growth chamber) conditions. Both northern and southern plants underwent a significant decrease in growth rate as a consequence of the treatment. Even so, plants appear to be quite resistant to SO2 compared with either more temperate or more productive species. The southern population was more sensitive to the treatment, as reflected by the bigger decrease in both growth and photosynthetic rates. Differences in resistance appear to be related to the biogeographic origin of the populations studied, which underlines the importance of biogeographic aspects in studies of resistance to air pollutants.     

Environmental health implications of heavy metal pollution from car tires

OBJECTIVE: To determine the effect of retinoic acid on wound healing of laser burns to explants of porcine retinal pigment epithelium (RPE). DESIGN: With the help of a mirrored attachment to a Coherent argon laser, laser burns (spot size 100 mu, power 500 mW, duration 0.2 seconds) were performed in 12 explants. The explants were then cultured in the presence (six explants) or absence (six explants) of 1 microM retinoic acid. Two explants in either group were recovered 4, 8 and 12 days after treatment for histologic study and scanning electron microscopy. OUTCOME MEASURE: Mean burn area remaining after culture. RESULTS: The area of wound remaining unhealed in the presence of retinoic acid was significantly larger than the area of wound remaining unhealed in the absence of retinoic acid at each time point. CONCLUSIONS: Retinoic acid inhibited wound healing of laser burns to porcine RPE. This effect may illustrate a role for retinoic acid in the pharmacotherapy of proliferative disorders.     

Domains of DnaA protein involved in interaction with DnaB protein, and in unwinding the Escherichia coli chromosomal origin

DnaA protein of Escherichia coli is a sequence-specific DNA-binding protein required for the initiation of DNA replication from the chromosomal origin, oriC. It is also required for replication of several plasmids including pSC101, F, P-1, and R6K. A collection of monoclonal antibodies to DnaA protein has been produced and the primary epitopes recognized by them have been determined. These antibodies have also been examined for the ability to inhibit activities of DNA binding, ATP binding, unwinding of oriC, and replication of both an oriC plasmid, and an M13 single-stranded DNA with a proposed hairpin structure containing a DnaA protein-binding site. Replication of the latter DNA is dependent on DnaA protein by a mechanism termed ABC priming. These studies suggest regions of DnaA protein involved in interaction with DnaB protein, and in unwinding of oriC, or low-affinity binding of ATP.     

Purification, characterization, and spasmogenic activity of neurotensin from the toad Bufo marinus

Neurotensin (NT) was isolated from an extract of the intestine of the cane toad, Bufo marinus and its primary structure established as: pGlu-Ala-Ile-Val-Ser-Lys-Ala-Arg-Arg-Pro-Tyr-Ile-Leu. This amino acid sequence shows five substitutions (Leu2 --> Ala, Tyr3 --> Ile, Glu4 --> Val, Asn5 --> Ser, and Pro7 --> Ala) compared with bovine NT. Synthetic Bufo NT (pD2 = 8.05 +/- 0.28) was equipotent and equally effective as bovine NT (pD2 = 8.24 +/- 0.38) in producing spasmogenic contraction of isolated segments of toad small intestine. However, the maximum response produced by Bufo NT was only 35 +/- 2% of that produced by substance P. The potencies, but not the maximum responses, to Bufo and bovine NT were significantly (p < 0.05) attenuated by pre-treatment with atropine but neither parameter was significantly diminished by tetrodotoxin and indomethacin. The data suggest that the action of NT involves interaction with receptors on toad intestinal smooth muscle that recognize the C-terminal region of NT (residues 8-13) that has been fully conserved during evolution of tetrapods. Contractile activity is mediated, at least in part, by release of acetylcholine.     

High phosphate level directly stimulates parathyroid hormone secretion and synthesis by human parathyroid tissue in vitro

Phosphate retention plays an important role in the pathogenesis of secondary hyperparathyroidism in patients with renal failure. In in vitro studies, high extracellular phosphate levels directly stimulate PTH secretion in rat and bovine parathyroid tissue. The present study evaluates the effect of high phosphate levels on the secretion of PTH and the production of prepro PTH mRNA in human hyperplastic parathyroid glands. The study includes parathyroid glands obtained from patients with primary adenomas and from hemodialysis and kidney-transplant patients with diffuse and nodular secondary hyperplasia. The experiments were performed in vitro using small pieces of parathyroid tissue. The ability of high calcium levels to decrease PTH secretion was less in adenomas than in secondary hyperplasia; among the secondary hyperplasia, nodular was less responsive to an increase in calcium than diffuse hyperplasia. In diffuse hyperplasia, PTH secretion was increased in response to 3 and 4 mM phosphate compared with 2 mM phosphate, despite a high calcium concentration in the medium; prepro PTH mRNA levels increased after incubation in 4 mM phosphate. Similar results were obtained with nodular hyperplasia, except that the elevation of PTH secretion in response to 3 mM phosphate did not attain statistical significance. In adenomas, high calcium concentrations (1.5 mM) did not result in inhibition of PTH secretion, independent of the phosphate concentration, and the prepro PTH mRNA was not significantly increased by high phosphate levels. In conclusion, first, the PTH secretory response to an increase in calcium concentration is less in nodular than diffuse hyperplasia; second, high phosphate levels directly affect PTH secretion and gene expression in patients with advanced secondary hyperparathyroidism.     

Comparative study in the rat of the actions of different types of stress on the release of 5-HT in raphe nuclei and forebrain areas

The effects of several stress procedures on the release of 5-HT in the dorsal and median raphe nuclei (DRN and MRN, respectively) and in forebrain structures of the rat brain innervated by both nuclei have been studied using intracerebral microdialysis. Handling for 30 sec, a saline injection and forced swimming for 5 min elevated significantly the 5-HT output in the MRN. The 5-HT output in the DRN was also enhanced by a saline injection. With regard to the forebrain structure examined, handling and forced swimming increased dialysate 5-HT in the amygdala. The injection of saline induced a slight, but significant, elevation of 5-HT in the medial prefrontal cortex. In contrast, the outflow of 5-HT was significantly reduced in the ventral hippocampus and medial prefrontal cortex following forced swimming and this effect persisted well beyond the cessation of the swim session. These results indicate that the efflux of 5-HT in the MRN appears to respond to different forms of stress, whereas that in the DRN only increases after the injection of saline. The release of 5-HT in the forebrain structures is also dependent on the type of stress procedure and the region studied.