Different clinical types of degenerative aphasia

The authors report 3 cases of slowly progressive aphasia with different language disturbances: anomia, pure word deafness and Broca's aphasia. All patients were independent in daily life activities. Insight, judgement and overall behaviour were intact. There was no major disturbance of other cognitive functions, but psychometric tests showed mild deficits suggesting widespread involvement. CT scans and magnetic resonance imaging showed focal dilatation of the left sylvian fissure. A positron emission tomographic study showed left perisylvian hypometabolism. A review of the literature yielded an increasing number of cases of this degenerative syndrome affecting dominant hemisphere language areas. Our cases confirm the clinical heterogeneity of degenerative aphasia. Postmortem neuropathological examinations are rare and many causes are found: Pick's disease, Alzheimer's disease or aspecific gliosis.     

Anatomic variations of the spermatic vein and endovascular treatment of left varicoceles: a pediatric series]

OBJECTIVE: To report on the high incidence of anatomical variants of the origin and course of the internal spermatic vein (ISV) discovered at the time of percutaneous embolization of left varicoceles in a pediatric population. METHODS: We reviewed retrospectively the 65 cases of left varicocele treated by percutaneous embolization (grade II and III) in our institution between 1990 and 2000. The course of the left renal vein (LRV), the origin of the ISV, and the number of ISVs and their pathway were recorded in all cases, according to the B?hren classification. RESULTS: In 37/65 (57%), the ISV was single and arose from a normal LRV (type I). The following variants were encountered: type V--circumaortic LRV 9/65 (14%); type IVb--intrarenal origin of ISV 8/65 (12%); type II--multiple ISV 5/65 (8%); and pelvic collaterals 6/65 (9%). CONCLUSION: Venous anatomical variants are frequently encountered (43%) at the time of left varicocele embolization in children. Such variants often impose some adjustments to the technique of embolization and, at times, hamper the procedure.     

Influence of Adrenal Glands on the Modulation of Prolactin Gene Expression by the Endogenous Benzodiazepine Ligand Octadecaneuropeptide in the Male Rat Pituitary Gland

Recently, an 86-amino acid polypeptide with high affinity for diazepam binding sites, termed diazepam-binding inhibitor (DBI), has been found in the rat brain. DBI, as well as a peptide derived from DBI, the octadecaneuropeptide DBI[33–50] (ODN), interacts with the GABA_A receptor complex. To investigate the role of these endogenous ligands for GABA_A receptors on prolactin gene expression, we studied the effects of acute intracerebroventricular administration (4  h before sacrifice) of ODN on prolactin mRNA levels in the male rat. Because, in some neuropeptidergic systems, glucocorticoids play a role in the response to ODN, we also studied the influence of adrenal glands and the effect of dexamethasone administration in the response of prolactin gene expression to ODN. ODN injection produced an increase in prolactin mRNA levels. Adrenalectomy performed 5 days before sacrifice resulted in an increase in prolactin gene expression and also potentiated the stimulating effect of ODN. Because castration has been shown to decrease prolactin gene expression in the male rat, we used castrated and adrenalectomized animals to study the role of dexamethasone in the response of lactotrophs to ODN. In these steroid-deprived animals, dexamethasone treatment (for 4 days) decreased prolactin mRNA levels but did not modify the response to ODN. These data indicate that an endogenous neuropeptide interacting with the GABA_A receptor complex can stimulate prolactin gene expression and suggest that the adrenal glands may produce factor(s) capable of decreasing prolactin mRNA. On the other hand, it does not appear that glucocorticoid hormones play a role in the effect of ODN on lactotroph activity.     

Differential changes of nicotinic receptors in the ratbrain following ibotenic acid and 192-IgG saporin lesionsof the nucleus basalis magnocellularis

The basal forebrain cholinergic neurons are implicated in the pathogenesis ofneurodegenerative diseases including Alzheimer^fn2s disease (AD). The nicotinic acetylcholine receptors (nAChRs) have been found to besignificantly afflicted in AD. To study the underlying mechanisms for dysfunction of the basalforebrain cholinergic neurons development of suitable animal models is warranted. In this studywe investigated the effects of bilateral lesions of the nucleus basalis magnocellularis on nAChRs inthe rat brain using the cholinergic system selective immunotoxin 192-IgG saporin andnon-selective excitotoxin ibotenic acid. Changes in nAChRs were measured by ³H-cytisineand ³H-epibatidine, two ligands with different selectivity for nAChRs subtypes. Inthe parietal cortex of ibotenic acid lesioned rates, the choline acetyltransferase activity (ChAT)was decreased by 24% while no changes were detected in the frontal cortex or hippocampus.Similarly, a 40% decrease was observed in the number of nAChRs labelled by ³H-cytisine,but not by ³H-epibatidine, in the parietal cortex, while no changes were found in thefrontal cortex or hippocampus. Although the 192-IgG saporin induced lesions reduced the ChATactivity in the frontal cortex, parietal cortex and hippocampus by 77, 50 and 21%, respectively, nochanges were observed in the number of nAChRs as studied by ³H-cytisine or ³H-epibatidine. The results indicate a difference in vulnerability of the cortical nAChRsubtypes to experimental lesions of the nucleus basalis magnocellularis. The findings in this studysuggest that a major portion of the nAChRs might be located on non-cholinergic neurons in thebrain.     

The atheroprotective effect of 17beta-estradiol depends on complex interactions in adaptive immunity

Estradiol prevents fatty streak formation in chow-fed atherosclerosis-prone apolipoprotein E (ApoE)-deficient mice. We previously reported that fatty streak development of immunodeficient ApoE(-/-)/recombination activating gene 2 (RAG-2(-/-)) double-deficient mice was insensitive to estradiol. In the present work, we demonstrate that the reconstitution of ApoE(-/-)/RAG-2(-/-) with bone marrow from immunocompetent ApoE(-/-)/RAG-2(+/+) mice restores the protective effect of estradiol on fatty streak constitution. We extended this demonstration to the model of low-density lipoprotein receptor-deficient mice, establishing the obligatory role of mature lymphocytes in this process. We then investigated whether the protective effect of estradiol was mediated by a specific lymphocyte subpopulation by studying the hormonal effect on fatty streak constitution in recently developed models of ApoE(-/-) mice deficient in selective T-lymphocyte subsets (either TCRalphabeta+, CD4+, CD8+, or TCRgammadelta+ lymphocytes) or B lymphocytes. In all these specifically immunodeficient mice, estradiol administration to ovariectomized mice conferred protection as in immunocompetent ApoE(-/-) mice, clearly demonstrating that no single lymphocyte subpopulation was specifically required for this effect. These results point to additional lymphocyte-dependent mechanisms such as modulating the interactions among lymphocytes and between lymphocytes and endothelial and/or antigen-presenting cells.     

Concentration and turnover of intraperitoneal hyaluronan during inflammation

Aseptic peritonitis was induced in rabbits by intraperitoneal injection of irritating agents, mainly starch suspensions. The inflammatory response was followed in the peritoneal lavage fluid by cell counts (average increase about 800-fold the first day) and hyaluronan concentration (average increase about 200-fold on the second and third days). The turnover rate of hyaluronan was studied by injecting tritium-labeled hyaluronan intraperitoneally and by following the appearance of tritiated water in serum. In control animals given trace amounts of hyaluronan, half-lives of 1–14 h were recorded. When the labeled polysaccharide had been mixed with 10 mg/ml of unlabeled hyaluronan, the half-life was approximately one day. Rabbits with ongoing peritonitis exhibited half-lives between 1 and 16 h. It was concluded that there was a large individual variation in uptake kinetics, that the removal process could be receptor mediated, and that the increase in intraperitoneal hyaluronan in peritonitis mainly was due to an increased production of the polysaccharide rather than a decreased rate of removal.     

Characterization of the poliovirus 147S particle: new insights into poliovirus uncoating

A Sabin 1 strain poliovirus (PV) mutant, S1(2Y-1I), carrying a Tyr at amino acid position VP2(142) and an Ile at position VP1(160), can establish persistent infections in HEp-2c cells. This mutant forms atypical 147S particles upon interaction at 0 degrees C with either cells expressing PV receptor (PVR) CD155, or PVR-IgG2a, a chimeric molecule consisting of an extracellular moiety of PVR and the hinge and Fc portion of a mouse IgG2a. Upon interaction with PVR at 37 degrees C, S1(2Y-1I), similar to the parental strain, forms both 135S A particles and 80S empty capsids. At 0 degrees C, surprisingly, at a concentration equal to or greater than 5 nM, PVR-IgG2a induced both the extrusion of VP4 from the capsid of S1(2Y-1I) and the formation of 80S particles. The same transitions were observed at 0 degrees C with the parental strain Sabin 1 at 40 nM PVR-IgG2a. Thus, the formation of 80S particles and VP4 extrusion, considered as one of the steps of PV uncoating, can be temperature-independent at high PVR concentration. This implies that structural changes of the PV capsid occurred following adsorption at low temperature.     

Autoantibodies directed against the amino-terminal domain I of human calpastatin (ACAST-DI Ab) in connective tissue diseases. High levels of ACAST-DI Ab are associated with vasculitis in lupus

To identify new autoantibody populations in patients with rheumatic diseases, a cDNA expression library was immunoscreened with a rheumatoid arthritis (RA) patient's serum which contains autoantibodies binding to uncharacterized polypeptides by Western-blotting. One clone encoding the amino-terminal region (Nt) [domain L and half of domain I] of human calpastatin was selected. Different fragments of the selected cDNA were prepared and the corresponding recombinant polypeptides were produced by in vitro translation and analysed by Western blotting. Most RA sera bound to recombinant amino-terminal region and domain I but not to domain L. This prompted us to use a recombinant polypeptide corresponding to the domain I of calpastatin as the antigen in a solid-phase ELISA to test sera from patients with various systemic rheumatic diseases and healthy controls.Anti-calpastatin domain I antibodies (ACAST-DI Ab), were detected by ELISA in RA, systemic lupus erythematosus (SLE), Sj?gren's syndrome and control sera at respective frequencies of 10, 9, 0 and 1%. These Ab did not have prognostic value in early RA; high levels were significantly associated with vasculitis in SLE. Antibodies reacting with the calpastatin amino-terminal region are produced during systemic rheumatic diseases and are predominantly directed against domain I. High levels of these Ab may constitute a marker of vasculitis in SLE.