The juxtamembrane domain (JMD) of N-cadherin cytoplasmic tail is an important regulatory region of the clustering and adhesion activities of the protein. In addition, the JMD binds a diversity of proteins capable of modifying intracellular processes including cytoskeletal rearrangement mediated by Rho GTPases. These GTPases also function as regulators of voltage-activated calcium channels, which in turn modulate neuronal excitability. The present study was designed to determine whether there is a direct functional link, via Rho GTPase, between the N-cadherin JMD and these voltage-activated channels. It was found that the infusion of the soluble JMD into chick ciliary neurons causes a substantial decrease in the amplitude of the high-threshold voltage-activated (HVA) calcium current. The activation time is increased while the inactivation process is reduced, suggesting that the decreased current amplitude reflects a reduction in the number of channels available to open. This effect was reversed by inhibition of RhoA or its downstream effector, Rho-associated kinase (ROCK). Because ROCK determines the active state of myosin, these results suggest that the modulation of HVA by the JMD could be mediated by changes in the status of the actin-myosin cytoskeleton.

Twelve cases of glomerulonephritis in patients without systemic diseases, displaying organized glomerular deposits, were reported. Microfibrils (ll-30nm diameter) were found in 9 patients and microtubules (20–35 nm diameter) in the other 3. Histochemical stainings for amyloid were always negative. By light microscopy, mesangial proliferative, membranous and membranoproliferative patterns were seen in 5, 3 and 4 patients, respectively. By immunofluorescence, granular deposits, mainly of IgG and C3, were found in all cases, either in the mesangium or in the mesangium and in the capillary walls. A second biopsy was performed in 2 patients. The number of hyaline glomeruli was increased, but the general pattern of glomerular changes remained unchanged. The commonest clinical findings were hypertension, microhematuria and proteinuria, often of nephrotic range. At variance to what is reported in the literature, 2 pediatric cases were found as well, and the overall prognosis (mean follow-up 54.3 months) was mostly favorable. The diagnostic relevance of these findings is pointed out, but further investigations are needed, before suggesting a new clinicopathological entity.

Patch tests were carried out to evaluate the presence of a sensitization to some components of dialytic circuits in 17 uremic patients complaining of pruritus of unknown origin. Fragments of different dialyzer membranes, of tubing sets, of dialyzer membranes recently resterilized with ethylene oxide and the International Contact Dermatitis Research Group standard series substances were tested. Neither patients nor healthy subjects reacted positively to patch tests, which leads us to question the role of contact allergy in the determination of uremic pruritus.

The mechanisms by which Ca2+ regulates light adaptation in microvillar photoreceptors remain poorly understood. Protein kinase C (PKC) is a likely candidate, both because some sub‐types are activated by Ca2+ and because of its association with the macromolecular ‘light‐transduction complex’ in Drosophila. We investigated the possible role of PKC in the modulation of the light response in molluscan photoreceptors. Western blot analysis with isoform‐specific antibodies revealed the presence of PKCα in retinal homogenates. Immunocytochemistry in isolated cell preparations confirmed PKCα localization in microvillar photoreceptors, preferentially confined to the light‐sensing lobe. Light stimulation induced translocation of PKCα immunofluorescence to the photosensitive membrane, an effect that provides independent evidence for PKC activation by illumination; a similar outcome was observed after incubation with the phorbol ester PMA. Several chemically distinct activators of PKC, such as phorbol‐12‐myristate‐13‐acetate (PMA), (‐)indolactam V and 1,2,‐dioctanoyl‐sn‐glycerol (DOG) inhibited the light response of voltage‐clamped microvillar photoreceptors, but were ineffective in ciliary photoreceptors, in which light does not activate the Gq/PLC cascade, nor elevates intracellular Ca2+. Pharmacological inhibition of PKC antagonized the desensitization produced by adapting lights and also caused a small, but consistent enhancement of basal sensitivity. These results strongly support the involvement of PKC activation in the light‐dependent regulation of response sensitivity. However, unlike adapting background light or elevation of [Ca2+]i, PKC activators did not speed up the photoresponse, nor did PKC inhibitors antagonize the accelerating effects of background adaptation, suggesting that modulation of photoresponse time course may involve a separate Ca2+‐dependent signal.

Small frameshift deletions within the COL4A5 gene were identified in three Alport syndrome Italian families by non-isotopic single-strand conformation polymorphism (SSCP) screening: in family RMA, a 7-bp deletion (GGGTGAA) in exon 39; in family DGR, a 4-bp deletion (TGGA) in exon 41; in family MIB, deletion of a G in exon 50. The phenotype was characterized by juvenile-onset renal failure with sensorineural hearing loss in males, and a milder clinical pattern in heterozygous females.