Epitope cleavage by Leishmania endopeptidase(s) limits the efficiency of the exogenous pathway of major histocompatibility complex class I-associated antigen presentation

The activation of CD8+ T cell responses is commonplace during infection with a number of nonviral pathogens. Consequently, there has been much interest in the pathways of presentation of such exogenous antigens for major histocompatibility complex class I-restricted recognition. We had previously shown that Leishmania promastigotes transfected with the ovalbumin (OVA) gene could efficiently target OVA to the parasitophorous vacuole (PV), with subsequent recognition by class II-restricted T cells. We now report the results of studies aimed at evaluating the PV as a route of entry into the exogenous class I pathway. Bone marrow-derived macrophages can present soluble OVA (albeit at high concentrations) to the OVA(257-264)-specific T cell hybridoma 13.13. In contrast, infection with OVA-transfected Leishmania promastigotes failed to result in the stimulation of this hybridoma. This appeared unrelated to variables such as antigen concentration, parasite survival, and macrophage activation status. These results prompted an analysis of the effects of promastigotes on class I peptide binding using RMA-S cells and OVA(257-264). Our data indicate that the major surface protease of Leishmania, gp63, inhibits this interaction by virtue of its endopeptidase activity against the OVA(257-264) peptide. The data suggest that this activity, if maintained within the PV, would result in loss of the OVA(257-264) epitope. Although we can therefore draw no conclusions from these studies regarding the efficiency of the PV as a site of entry of antigen into the exogenous class I pathway, we have identified a further means by which parasites may manipulate the immune repertoire of their host.     

Differential expression of mammalian TRP homologues across tissues and cell lines

Mammalian homologues of the Drosophila trp gene have been invoked as the structural basis for the currents associated with capacitative Ca2+ entry (CCE) in many cell types. Trp homologues are members of a large protein family that may associate as channel subunits providing an explanation for the functional diversity of store-operated channels observed in these cells. However, there is little information as to which of these genes are co-expressed at the cellular level. We have examined the tissue specific expression of five mammalian trp genes and determined which are co-expressed in five different cell lines. The results show tissue- and cell-specific co-expression of multiple trp forms. This implies that the subunit composition of a particular CCE channel may vary depending on the cell type.     

Carrageenan given as a jelly, does not initiate, but promotes the growth of aberrant crypt foci in the rat colon

We report a case of sperm cell seminoma caused by trauma. The data in the literature indicate the frequency is less than 5% of all seminomas. This case was exclusively located in the gonads and was a pure form. Orchidectomy with high ligature of the cord and adjuvant radiotherapy at the dose of 25 Gy centered on the para-aortic and subdiaphragmatic chains is adequate treatment. When inguinoscrotal surgery is performed, this zone must be irradiated with 25 Gy. Prognosis is satisfactory: 5-year survival is 100% with this protocol.     

Presentation and treatment of spontaneous aortocaval fistula

BACKGROUND: Spontaneous rupture of abdominal aortic aneurysm into the inferior vena cava is rare. The clinical presentation is highly variable, and the diagnosis can be difficult, often being made only at operation. The aortocaval fistula results in a large left-to-right shunt, which can cause cardiac failure. Once the diagnosis is made, treatment is by surgical closure of the fistula and repair of the aneurysm with a graft. METHODS: This is a retrospective review of a single surgeon's experience with aortocaval fistula complicating abdominal aortic aneurysms. RESULTS: Over a 15-year period, we had five patients with spontaneous aortocaval fistula who were treated operatively. Preoperative diagnosis was made in two, suspected in one, and not made in two, one of whom died (the only perioperative death in the series). CONCLUSIONS: Spontaneous aortocaval fistulas are uncommon, and their preoperative recognition is difficult. Hematuria in association with an abdominal aortic aneurysm should raise the suspicion of an aortocaval fistula. Surgical correction is possible, with survival rates comparable to those associated with rupture of aneurysms into the retroperitoneum. Early operative control of the fistula is important to optimize the preload to the heart.     

Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome

Prostaglandin E2 levels in isolated rat islets were increased from 64 +/- 11 pg/30 islets when incubated in medium containing 2 mM glucose to 115 +/- 9 pg/30 islets in medium containing 20 mM glucose. In contrast, glyceraldehyde (10 mM) reduced prostaglandin E2 levels to 29 +/- 6 pg/30 islets. Inhibition of glucose metabolism by mannoheptulose (10 mM) abolished the stimulatory effect of glucose on prostaglandin E2 levels and inhibited glucose-induced insulin release. The cyclooxygenase inhibitor, flurbiprofen (20 microM), did not affect insulin release caused by glucose or glyceraldehyde. In the presence of 1 mg/ml bovine serum albumin, insulin secretion induced by 20 mM glucose (6.9 +/- 1.1% of islet insulin content) was reduced by the lipoxygenase inhibitor BW755 C (20 microM) to 3.1 +/- 0.6%, and by the phospholipase A2 inhibitor, p-bromophenacyl bromide (10 microM), to 2.1 +/- 0.8%. In the absence of bovine serum albumin the inhibitory action of BW755 C and p-bromophenacyl bromide on glucose-induced insulin release was significantly more pronounced. These drugs whether in the presence or absence of bovine serum albumin, did not affect glyceraldehyde-stimulated insulin secretion. Glyceraldehyde (10 mM), potentiated glucose-induced insulin release in the presence of 2-8 mM glucose, but not for 10-20 mM glucose. Although the phospholipase A2 activator, melittin, initiated insulin release in the presence of 2 mM glucose and enhanced 10 mM glyceraldehyde-stimulated insulin secretion it had no effect on 20 mM glucose-induced insulin release. These two stimulatory effects of melittin on insulin release were totally abolished by p-bromophenacyl bromide.(ABSTRACT TRUNCATED AT 250 WORDS)     

The D2 autoreceptor agonists SND 919 and PD 128483 decrease stereotypy in developing rats

Although stereotyped behavior in adult rats is partly regulated by dopamine (DA) D2 autoreceptors, previous attempts to demonstrate D2 autoreceptor regulation of stereotypy in developing rats have been unsuccessful. In the present study, two highly selective D2 autoreceptor agonists were used to demonstrate D2 autoreceptor regulation of spontaneous stereotyped behavior in developing rats. Both SND 919 and PD 128483 produced significant dose-dependent decreases in the stereotypy counts of 21-day-old, 35-day-old, and adult rats. There was a 51% decrease in the stereotypy counts of 21-day-old rats injected with SND 919, 0.05 mg/kg, compared to a 36% decrease in the counts of rats pretreated with haloperidol. Similarly, PD 128483 significantly decreased the stereotypy counts of 21-, 35-day-old, and adult rats in a dose-dependent fashion. There was a 58% decrease in the stereotypy counts of 21-day-old rats injected with PD 128483, 0.1 mg/kg, compared to a 17% decrease in counts when the rats were first treated with haloperidol. The effect of haloperidol plus PD 128483 was significantly different from the effect of PD 128483 alone. Injection of SND 919 or PD 128483 had no significant effects on the stereotypy counts of 10-day-old rats. The results suggest that DA D2 autoreceptor-mediated regulation of spontaneous stereotyped behavior is functional at 21, but not 10, days of age.     

Monoamine oxidase inhibitors inhibit [3H]quinpirole binding in rat striatal membranes

The paper deals with methods facilitating the preparation of oncospheres of the cestode, Hymenolepis diminuta, for experimental studies. Described in detail are procedures for the infection of the definitive hosts with the oncospheres; collection and artificial hatching of oncospheres; purification of hexacanths; preparation of extracts from the hexacanths; and preparation of hexacanths for electronmicroscopic studies.