New evidence from blocking desmosomal adhesion with anti-adhesion peptides reveals a role for desmosomes in cell positioning in morphogenesis. Desmosomal adhesion is necessary for the stability of adherens junctions in epithelial cell sheets. Knockout and mis-expression of desmosomal cadherins in mice suggests that they may function directly or indirectly in regulating epidermal differentiation. Protein kinase C signalling and tyrosine phosphorylation appear to regulate desmosomal adhesion. There are new insights into the role of desmosomal cadherins in autoimmune, infectious and genetic disease.

In normal men, the majority of GH secretion occurs in a single large postsleep onset pulse that is suppressed during total sleep deprivation. We examined the impact of semichronic partial sleep loss, a highly prevalent condition, on the 24-h growth hormone profile. Eleven young men were studied after six nights of restricted bedtimes (0100-0500) and after 7 nights of extended bedtimes (2100-0900). Slow-wave sleep (SWS) was estimated as the duration of stages III and IV. Slow-wave activity (SWA) was calculated as electroencephalogram power density in the 0.5- to 3-Hz frequency range. During the state of sleep debt, the GH secretory pattern was biphasic, with both a presleep onset "circadian" pulse and a postsleep onset pulse. Postsleep onset GH secretion was negatively related to presleep onset secretion and tended to be positively correlated with the amount of concomitant SWA. When sleep was restricted, both SWS and SWA were increased during early sleep. Unexpectedly, the increase in SWA affected the second, rather than the first, SWA cycle, suggesting that presleep onset GH secretion may have limited SWA in the first cycle, possibly via an inhibition of central GH-releasing hormone activity. Thus neither the GH profile nor the distribution of SWA conformed with predictions from acute sleep deprivation studies, indicating that adaptation mechanisms are operative during chronic partial sleep loss.

Desmosomes are adhesive intercellular junctions of epithelia and cardiac muscle. They have an essential function in maintaining the integrity of tissues, which is compromised in human genetic and autoimmune disease that targets desmosomal components. Recent evidence (1) suggests new roles for the function of desmosomal adhesion in tissue morphogenesis, (2) gives new insights into the molecular mechanism of adhesion, (3) indicates that the desmosomal adhesion molecules, desmocollin and desmoglein, may contribute to the regulation of epidermal diffentiation, and (4) shows that the affinity of desmosomal adhesion is regulated by protein kinase C.

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To the EditorIt is generally accepted that the majority of bullous pemphigoid (BP) sera and a considerable number of cicatricial pemphigoid (CP) sera recognize a hemidesmosomal component BP180 (Labib et al, 1986;Bernard et al, 1992). CP, however, shows different clinical features from BP. Usually, CP has a predominant involvement of oral and ocular mucous membranes with a tendency of scarring. The different clinical features between BP and CP might be due to different targeted epitopes on this antigen, or to a difference of immunoglobulin classes. Therefore, in this study, we produced three bacterial glutathione-Stransferase (GST) fusion proteins, named GST-BP-1050, GST-BP-963, and GST-BP-915, and examined their reactivities with BP and CP sera.GST-BP-1050 encodes N-terminal 350 amino acids (542-892); GST-BP-963 encodes central 321 amino acids (885-1206); and GST-BP-915 encodes C-terminal 305 amino acids (1227-1532) of BP180 extracellular domain (BP180 ECD) (sequence data referred to Giudice et al, 1992). Put together, these three fusion proteins roughly cover the whole BP180 ECD. To produce these fusion proteins, three constructs were generated by inserting three appropriate polymerase chain reaction-amplified fragments of BP180 cDNA into bacterial vectors pGEX (Pharmacia, Uppsala, Sweden) (pGEX-3X for GST-BP-1050, pGEX-2T for GST-BP-963 and GST-BP-915). The resulted constructs were used to transform E. coli XL-Blue (Stratagene, La Jolla, CA) or BL21 (Pharmacia, Uppsala, Sweden) (to reduce the degradation of fusion proteins, BL21 was used for GST-BP-963 and GST-BP-915). All constructs were sequenced to confirm the identity and fidelity of subcloning steps. Fusion proteins were induced by IPTG and purified by glutathione-agarose affinity columns as described previously (Matsumura et al, 1996). The fusion proteins were of expected sizes as judged by a polyclonal anti-GST antibody (G-7781, Sigma, St. Louis, MO), i.e., GST-BP-1050 (top band) being 66 kDa, GST-BP-963 being 62 kDa, GST-BP-915 being 60 kDa. The reactivity of fusion proteins with 20 BP sera, 10 CP sera and 10 normal control sera, were analyzed by immunoblotting as described previously (Hashimoto et al, 1990). By direct immunofluorescence, all BP exhibited IgG and all CP showed both IgG and IgA deposits in BMZ. By indirect immunofluorescence, all BP and CP sera showed IgG antibodies against the epidermal side of salt-split skin. Four CP but no BP sera showed IgA anti-BMZ antibodies. These CP patients had oral and ocular involvement and healed with scarring.The representative results were shown in Fig 1 . Seventeen (85%), five (25%), and six (30%) BP sera showed IgG antibodies reactive with GST-BP-1050, GST-BP-963, and GST-BP-915, respectively. Three (15%) BP sera reacted with all three fusion proteins. Only one BP serum reacted exclusively with GST-BP-915. No BP sera showed IgA antibodies reactive with any fusion proteins. For CP, five (50%), one (10%), and five (50%) sera showed IgG antibodies reactive with GST-BP-1050, GST-BP-963, and GST-BP-915, respe...