Xenopus oocytes indicates that calcium-activated chloride currents are evoked by PACAP and vasoactive intinal polypeptide, sggesting that PACAPR-3 can also be coupled to phospholipase C. RNA blot analysis studies reveal that PACAPR-3 mRNA is expressed at high levels in MIN6, at moderate levels in pancreatic islets and other insulin-secreting cell lines, HIT-T15 and RINm5F, as well as in the lung, brain, stomach, and colon, and at low levels in the heart. Furthermore, insulin secretion from MIN6 cells is scantiy stimulated by PACAP-38. These results suggest that the diverse biological effects of PACAP are mediated by a family of structurally related proteins and that PACAPR-3 participates in the regulation of insulin secretion.

There has recently been an increase in data indicating that autoimmune mechanisms are involved in the etiopathogenesis of idiopathic thrombocytopenic purpura (ITP) (1, 2). Although antibodies that react with platelets are found in most patients with ITP, the pathogenetic nature of the antibodies remains to be clarified . The discovery of an animal model for ITP has therefore been long-awaited. Here we have found that (NZW x BXSB)Fi (W/B Fi) mice, which develop lupus nephritis with myocardial infarction (3), show thrombocytopenia with age, and that this is due to the presence ofboth platelet-associated antibodies (PAA) and circulating antiplatelet antibodies.Recently, we have demonstrated that allogeneic bone marrow transplantation (ABMT) has curative effects on autoimmune diseases in (NZB x NZW)FI, BXSB, MRL/MP-lpr/lpr (MRL/lpr), and NOD mice (4-6) . These results prompted us to examine whether ABMT can be used to treat ITP. In the present study, we provide evidence that the transplantation of bone marrow from BALB/c mice to W/B F, mice does indeed have preventative and curative effects on ITP Materials and MethodsMice.Mice ofthe inbred strain BALB/c nu/nu, BALB/c, C57B/6, C3H/HeN, BXSB, NZW were raised under specific pathogen-free conditions in our animal facility. W/B F, males were obtained from the Nippon Shinyaku Research Laboratories, Kyoto, Japan.Staining Procedure andData Analysis.Platelet-rich plasma was obtained as described previously (7) . The platelets were suspended in 1% paraformaldehyde solution for 5 min. After

SummaryBlood glucose levels of streptozocin (STZ)-induced diabetic rats dropped from hyperglycemic levels to hypoglycemic levels within 24-48 h after treatment with vanadyl sulfate (VS) by intraperitoneal injection. Results of the glucose tolerance test indicated that the diabetes was completely improved by VS administration, but the plasma insulin levels were still low. Determination of both vanadyl and total vanadium in VS-treated STZ-rats suggested that the vanadyl is possibly in a pharmacologically active form. Several vanadyl complexes such as vanadyl-cysteine methyl ester (VCys), -oxalate (VOX), -malonate (VMA), -salicylaldehyde (VSA) , and -(+)-tartarate (VTA) were tested by oral administration. The order of normoglycemic effect in STZ-rats was VMA > VCys > VTA > VSA > VOX. The action of VCys was dosedependent in the range of 1-10 mg V/kg body weight, and this complex was shown to be a potent agent in restoring the normoglycemic level in STZ-induced diabetic rats.

Recent studies have suggested that abnormalities in the adenomatous polyposis coli gene (APC gene) are associated with the development not only of familial adenomatous polyposis coli (FAP) but also of cancers in digestive organs. In order to elucidate whether abnormalities of the APC gene could contribute to the development of oral squamous-cell carcinoma (SCC), genomic DNAs from tumors and normal tissues of 24 unrelated Japanese patients were examined by using PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) and sequence analyses. Five novel nucleotide substitutions of the APC gene in tumor tissues were identified in 3 patients with oral SCC (12.5%), resulting in 3 amino-acid replacements or a truncation of the APC gene product. We also examined 24 tumor and 24 normal tissue samples for loss of heterozygosity (LOH) at exon 11 of the APC gene by PCR-LOH assay. In this analysis, 45.8% of samples were informative and LOH was detected in 72.7% of informative cases. The frequency of LOH in oral SCC was similar to that previously reported in esophageal SCC. These results suggest that abnormalities in the APC gene are associated with the development of human oral SCC.