Dibutyryl-cAMP induces SNAP-25 translocation into the neurites in PC12.

SNAP-25 immunoreactivity was translocated into the endings of the processes induced in PC12 cells by dibutyryl-cAMP-treatment. Conversely, the protein was not present in the endings of the processes seen after NGF-treatment unless dibutyryl-cAMP was used simultaneously. This redistribution of SNAP-25 immunoreactivity appeared to be dependent upon new protein synthesis. Finally, dibutyryl-cAMP was capable of inducing SNAP-25 expression.     

Epidemiological study of myasthenia gravis in Sardinia, Italy (1958–1986)

From 1.1.1958 to 31.12.1986, 110 cases of MG were observed in Sardinia, with a mean annual incidence of 2.5 x 1,000,000 inhabitants and prevalence rates of 7.5, 17.6, 31.4 and 45.0 x 1,000,000 inhabitants respectively (prevalence days: 15.10.1961, 24.10.1971, 25.10.1981 and 31.12.1986). The disease was found to be more frequent in women. There were no differences in the distribution of MG in various areas of the island. The muscle group more frequently involved at onset was the ocular. In 6.4% of patients an association with thyroid disorders was observed. The mortality of MG patients was significantly higher than expected. Removal of the thymus, carried out in 58 patients, was shown to be useful in the treatment of the disease, particularly in patients without thymomas. No familial cases were observed.     

1,2,3-triazolo[4,5-f]quinolines. II. Preparation and antimicrobial evaluation of 6-ethyl-6,9-dihydro-1(2)(3)-R-1(2) (3)H-triazolo [4,5-f]quinolin-9-one-8-carboxylic acids as anti-infectives of the urinary tract (1)

Some 6-ethyl-1(2)(3)-R-1(2)(3)H-triazolo[4,5-f]quinolin-9-one-8-carboxy lic acids were prepared as novel analogues of oxolinic acid in order to evaluate the effect on antibacterial activity of the isosteric replacement of the dioxolic moiety with the triazole ring substituted in position 1 or 2. In vitro tests showed a good and selective activity against Escherichia coli (MIC 12.5 micrograms/ml) of compound (XVI).     

Activated Protein C Reduces Graft Neutrophil Activation in Clinical Renal Transplantation

We studied the role of endogenous activated protein C (APC), the major physiological anti-coagulant with concomitant anti-inflammatory properties, on ischemia/reperfusion (I/R) in 45 patients participating in a larger trial comparing three immunosuppressive protocols in cadaveric renal transplantation: perioperative anti-thymocyte globulin (ATG, Fresenius AG, Bad Homburg, Germany), perioperative basiliximab and conventional triple therapy. Blood samples for assessing plasma APC, protein C, and lactoferrin concentrations, neutrophil CD11b and L-selectin expressions and blood leukocyte differential counts were obtained preoperatively and before reperfusion from central venous cannula, complemented with simultaneous samples from iliac artery and graft vein for calculation of transrenal differences (Delta) of study parameters at 1 and 5 min after reperfusion. Unlike basiliximab or conventional therapy groups, ATG infusion induced a substantial increase in plasma APC concentration (119 [88-144]% before infusion vs. 232 [85-1246]% after infusion, p<0.001), resulting in renal graft sequestration of APC at 1 min after reperfusion (Delta=-72 [-567 to 12]%, p<0.001). Graft APC consumption was associated with transrenal reduction of neutrophil activation markers (L-selectin r=0.7, p=0.01; lactoferrin r=-0.6, p=0.02; CD11b r=-0.8, p=0.001), and with both warm (r=0.6, p=0.01) and cold ischemia time (r=0.6, p=0.02) and donor age (r=0.6, p=0.01). These findings suggest that APC has an anti-inflammatory role in I/R injury in clinical renal transplantation.     

Distribution and ontogeny of parvalbumin immunoreactivity in the chicken retina.

The distribution of parvalbumin-like immunoreactivity was studied in the embryonic and postnatal chicken retina. In post-hatched chickens, parvalbumin-like immunoreactivity was confined to amacrine cells. Three distinct subpopulations were identifiable based upon soma position and level of dendritic arborization in the inner plexiform layer. The primary dendrites from parvalbumin-immunoreactive amacrine cells descended vertically into the inner plexiform layer and eventually branched to give rise to a laminarly arrayed plexus in sublamina I, sublamina V and, to a lesser extent, at the boundary between sublaminae III and IV. Parvalbumin-like immunoreactive amacrine cells projecting to sublamina I of the inner plexiform layer were consistently monostratified. Some, but not all, contributed thick fibers to sublamina I that could be followed for long distances across the retina and were generally not radially organized. The parvalbumin-like immunoreactive cells that projected to sublamina V gave rise to a primary dendrite from which three to five fibers branched radially. Collateral branches of these same primary dendrites gave rise to the parvalbumin-like immunoreactive plexus at the interface between sublaminae III and IV. In prenatal chickens, parvalbumin-like immunoreactivity was not detected until embryonic day 14. At this time it appeared as a faint band at the inner nuclear layer-inner plexiform layer boundary in the central retina. By embryonic day 18 the intensity of immunoreactivity and the complexity of the arborizations of the parvalbumin-like immunoreactive dendrites approached that seen in the post-hatched chicken. In the chicken retina, parvalbumin-like immunoreactivity was displayed by morphologically distinct subpopulations of amacrine cells suggesting that these amacrine cells may subserve diverse functions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Haemophilia A: molecular insights.

Haemophilia A is the most common inherited bleeding disorder caused by defects in the F8C gene that encodes coagulation factor VIII. This X-linked recessive disorder occurs in approximately 1:5000 males. Haemophilia A is diagnosed based on normal prothrombin time, altered activated partial thromboplastin time and reduced factor VIII activity in plasma. Carrier females are usually asymptomatic and can be identified only by molecular analysis. The most frequent mutations in F8C are intron 22 and 1 inversions, which occur in approximately 50% and 5% of patients, respectively, with a severe phenotype. Large gene deletions are observed in approximately 5% of alleles from patients with severe haemophilia A. The remaining severe cases and all moderate and mild cases result from numerous point mutations and small insertions/deletions, which are de novo mutations in one-third of cases. Thus, molecular diagnosis of carrier status and prenatal diagnosis in families without intron 22 or 1 inversions is based on scanning techniques or gene sequencing. When the disease-causing mutation cannot be identified, molecular diagnosis is performed by linkage analysis of several DNA polymorphic markers linked to F8C. Given the clinical heterogeneity among haemophilic patients, many groups, including our own, have examined the relationships between prothrombotic gene variants and haemophilic phenotype to investigate whether prothrombotic gene variants modify clinical expression of the disease.     

Family studies of relation between Perthes disease and congenital dislocation of the hip

A family study of Perthes disease and congenital dislocation of the hip was made in the Faroe Islands, with a population of 40 000. The examination included 1123 sibs and first cousins of 43 probands with Perthes disease, 1942 sibs and first cousins of 59 dislocation probands, and 5205 sibs and first cousins of 172 unaffected matched controls. Both conditions occur with exceptionally high incidences in this population. Thus the incidence of Perthes disease was found to be 41: 10 000 males and 7: 10 000 females, of congenital dislocation of the hip 7: 10 000 males and 59: 10 000 females. These figures are 3 to 4 times higher than those commonly observed in Caucasian populations.

Among the 1123 relatives of Perthes probands, we found 10 cases of Perthes disease and 9 cases of dislocation; among the 1942 relatives of dislocation probands, there were 11 cases of Perthes disease and 23 cases of dislocation. Thus both disorders show an accumulation within the same families. On the other hand among the 5205 relatives of probands selected because the hips were unaffected, we found only 3 cases of Perthes disease and 10 cases of dislocation.

Considering the conspicuously low familial accumulation of Perthes disease seen in a low-risk population elsewhere (South Wales), the high incidence of the two disorders and the simultaneously strong intrafamilial accumulation in the Faroe population seem to indicate that the search for exogenous influences, specific to this area, should be intensified.