Large gangliocytic paraganglioma of the duodenum: A rare entity

Gangliocytic paragangliomas are rare tumors that almost exclusively occur within the second portion of the duodenum. Although these tumors generally have a benign clinical course, they have the potential to recur or metastasize to regional lymph nodes. The case report presented here describes a 57-year-old female patient with melena, progressive asthenia, anemia, and a mass in the second-third portion of the duodenum that was treated by local excision. The patient was diagnosed with a friable bleeding tumor. The histologic analysis showed that the tumor was a 4 cm gangliocytic paraganglioma without a malignant cell pattern. In the absence of local invasion or distant metastasis, endoscopic resection represents a feasible, curative therapy. Although endoscopic polypectomy is currently considered the treatment of choice, it is not recommended if the size of the tumor is > 3 cm and/or there is active or recent bleeding. Patients diagnosed with a gangliocytic paraganglioma should be closely followed-up for possible local recurrence.     

Missense mutations in codon 225 of ornithine transcarbamylase (OTC) result in decreased amounts of OTC protein: A hypothesis on the molecular mechanism of the OTC deficiency

Mutations P225L and P225R were identified in codon 225 of the gene for ornithine transcarbamylase (OTC) in two patients with the neonatal form of OTC deficiency. The mutations occur at a CpG dinucleotide and eliminate a unique MspI restriction site in exon 7 of the OTC gene. They do not alter existing splice sites or create new sites, as judged from the nucleotide sequence. Both mutations are associated with undetectable levels of OTC antigen in liver homogenates, and with either complete lack of OTC activity (P225R mutation) or very small residual activity (0.15% of normal in the P225L mutation). The residual activity observed with P225L exhibits normal pH dependence, little or no increases in the Km values for ornithine and carbamoyl phosphate and normal stability at either 37°C or, in the presence of 0.66 mol/L urea, at 0°C. The latter conditions were used to examine whether the P225L mutation favours dissociation of the active OTC trimer. Given the normal stability and lack of tendency to dissociation of the mutant enzyme, it appears likely that the dramatic reduction in the level of OTC protein is due to inefficient conversion of the mutant OTC precursor polypeptide (pOTC) into the correctly localized, appropriately folded, mature enzyme trimer, suggesting degradation of pOTC in transit to the mitochondria.     

Familias Unidas: The Efficacy of an Intervention to Promote Parental Investment in Hispanic Immigrant Families

This paper reports a test of the efficacy of Familias Unidas, a Hispanic-specific, ecologically focused, parent-centered preventive intervention, in promoting protection against and reducing risk for adolescent behavior problems. Specifically, the intervention was designed to foster parental investment, reduce adolescent behavior problems, and promote adolescent school bonding/academic achievement, all protective factors against drug abuse and delinquency. One-hundred sixty seven Hispanic families of 6th and 7th grade students from three South Florida public schools were stratified by grade within school and randomly assigned to intervention and no-intervention control conditions. Results indicated that Familias Unidas was efficacious in increasing parental investment and decreasing adolescent behavior problems, but that it did not significantly impact adolescent school bonding/academic achievement. Summer-vacation rates of adolescent behavior problems were six times higher in the control condition than in the intervention condition. Furthermore, change in parental investment during the intervention was predictive of subsequent levels of adolescent behavior problems. The findings suggest that Familias Unidas is efficacious in promoting protection and reducing risk for adolescent problem behaviors in poor immigrant Hispanic families.     

Development of DNA vaccines against hemolytic-uremic syndrome in a murine model

Shiga toxin type 2 (Stx2) produced by Escherichia coli O:157H7 can cause hemolytic-uremic syndrome in children, a disease for which there is neither a vaccine nor an effective treatment. This toxin consists of an enzymatically active A subunit and a pentameric B subunit responsible for the toxin binding to host cells, and also found to be immunogenic in rabbits. In this study we developed eukaryotic plasmids expressing the B subunit gene of Stx2 (pStx2B) and the B subunit plus the gene coding for the A subunit with an active-site deletion (pStx2 Delta A). Transfection of eukaryotic cells with these plasmids produced proteins of the expected molecular weight which reacted with specific monoclonal antibodies. Newborn and adult BALB/c mice immunized with two intramuscular injections of each plasmid, either alone or together with the same vector expressing the granulocyte and monocyte colony-stimulating factor (pGM-CSF), elicited a specific Th1-biased humoral response. The effect of pGM-CSF as an adjuvant plasmid was particularly notable in newborn mice and in pStx2B-vaccinated adult mice. Stx2-neutralizing activity, evaluated in vitro on VERO cell monolayers, correlated with in vivo protection. This is the first report using plasmids to induce a neutralizing humoral immune response against the Stx2.     

Histological study of the proximal and distal segments of the embryonic outflow tract and great arteries

The normal development of the ventricular outlets and proximal region of the great arteries is a controversial subject. It is known that the conus, truncus arteriosus (truncus), and aortic sac participate; however, there are some doubts as to the actual prospective fate of the truncus. Some authors propose that it gives origin to the proximal region of the great arteries and that the myocardial cells of its wall become smooth muscle. Nevertheless, others think that the truncus only forms the arterial valve apparatus and that therefore the myocardial cells transform into fibroblasts. As a first approach to beginning to elucidate which process occurs, the aim of this article was to study the histological changes in the wall of these components of the developing heart in chick embryos whose hearts had been labeled at the truncoconal boundary at stage 22HH, tracing the changes up to stage 36HH. Also, the histological constitution of the wall of the pulmonary arterial trunk and its valve apparatus were studied in the posthatching and adult hearts of chickens and rats. The conus and truncus walls were always encircled by a myocardial sleeve from the outset of their development. Between stages 26HH to 28HH, the truncal myocardial cells adjacent to the mesenchymal tissue of the ridges began to lose cell-to-cell contacts and invaded the extracellular matrix. At stage 24HH, the aortic sac began to project into the pericardial cavity and became divided into two channels by the aortic-pulmonary septum at stage 26HH. The wall of the aortic sac is mostly constituted by a compact mesenchymal tissue. Initially, it does not have smooth muscle but this starts to appear at stage 30HH. The insertion ring of the valves, a broad structure, was formed by mesenchymal tissue. Both structures were always covered by a myocardial sleeve. The leaflets developed from the truncal ridges, the segment immediately proximal to the aortic sac. Our results indicate that the proximal region of the pulmonary and aortic arteries do not originate from the truncus arteriosus; rather, we found that they take origin from the aortic sac. Thus, our findings agree with the proposal that the myocardial cells of the external sleeve of the truncus become fibroblastic and suggest that the insertion ring of the arterial valves has a dual origin: fibroblasts produced by truncal myocardial transdiferentiation and the mesenchymal tissue of the proximal region of the truncal ridges, while the leaflets have their origin from the truncal ridges. We discuss the fact that, because the truncus arteriosus does not give origin to the trunks of the aortic and pulmonary arteries, it may be necessary to modify terminology. Based on our results, together with the new findings obtained by in vivo labeling, immunostaining, a chimeric approach, and ultrastructural studies, we propose a developmental model that correlates the fate of the conus, truncus, and aortic sac with the normal morphogenesis of the ventricular outlet tracts and the trunks of the great arteries. (c) 2005 Wiley-Liss, Inc.     

Choroiditis and meningitis in experimental murine infection withListeria monocytogenes

In a study of central nervous system involvement in experimental listeriosis 27 Swiss CD1 mice were inoculated subcutaneously withListeria monocytogenes. Systemic infection developed, as shown by the isolation ofListeria monocytogenes and histopathological lesions in the spleen and liver. In the central nervous system a mixed inflammatory infiltration in the ventricular system, especially in the choroid plexus, and leptomeningitis were the most relevant lesions. Inflammatory lesions were associated with the presence ofListeria monocytogenes, as demonstrated by a positive anti-Listeria monocytogenes immunoperoxidase reaction within phagocytic cells. It is suggested that choroiditis and meningitis developed as a consequence of hematogenous dissemination ofListeria monocytogenes within mononuclear phagocytes and penetration of these cells into the ventricular system through the choroid plexus.     

Role of Elastin in Spontaneously Hypertensive Rat Small Mesenteric Artery Remodelling

Chronic hypertension is associated with resistance artery remodelling and mechanical alterations. However, the contribution of elastin has not been thoroughly studied. Our objective was to evaluate the role of elastin in vascular remodelling of mesenteric resistance arteries (MRA) from spontaneously hypertensive rats (SHR). MRA segments from Wistar Kyoto rats (WKY) and SHR were pressurised under passive conditions at a range of physiological pressures with pressure myography. Confocal microscopy was used to determine differences in the quantity and organisation of elastin in intact pressure-fixed arteries. To assess the contribution of elastin to MRA structure and mechanics, myograph-mounted vessels were studied before and after elastase incubation. When compared with WKY, MRA from SHR showed: (1) a smaller lumen, (2) decreased distensibility at low pressures, (3) a leftward shift of the stress-strain relationship, (4) redistribution of elastin within the internal elastic lamina (IEL) leading to smaller fenestrae but no change in fenestrae number or elastin amount. Elastase incubation (1) fragmented the structure of IEL in a concentration-dependent fashion, (2) abolished all the structural and mechanical differences between strains, and (3) decreased distensibility at low pressures. The study shows the overriding role of elastin in determining vascular dimensions and mechanical properties in a resistance artery. In addition, it informs hypertensive remodelling. MRA remodelling and increased stiffness are accompanied by elastin restructuring within the IEL and elastin degradation reverses structural and mechanical alterations of SHR MRA. Differences in elastin organisation are, therefore, a central element in small artery remodelling in hypertension.     

A microbiological, histopathological and immunohistological study of the intragastric inoculation of Listeria monocytogenes in mice.

The course of murine infection after intragastric inoculation of L. monocytogenes was investigated by immunocytochemical, histopathological and microbiological techniques. L. monocytogenes antigen was observed in epithelial cells of intestinal mucosa overlying Peyer's patches, but not in mucosa devoid of them. This suggests that penetration of L. monocytogenes into the host organism may take place through epithelium overlying Peyer's patches. The efficiency of bacterial penetration appeared to be low, as shown by the small amounts of L. monocytogenes antigen detected and the low counts of bacteria in organs. Gross or histopathological lesions in the intestinal tract were not observed. The presence of L. monocytogenes in spleen, liver and in maxillary and mesenteric lymph nodes, confirmed that the systemic course of infection by this route of inoculation is similar to that of the parenteral routes. The results emphasize the subclinical character of murine listeriosis by the oral route.