No abstract

The incidence of malignant melanoma is much lower in the Japanese than in caucasians. However, amongst the various types of malignant melanoma, the subungual and periungual sites are commonly found in the Japanese. One hundred and fifty-one cases of cutaneous malignant melanoma were seen over a 25-year period at our hospital. We found that, in 34 patients (23%), the subungual region was involved, a high frequency for one institution. We have analysed these patients and looked at their treatment. The finger nails were affected in 21 cases (62%) and the toe nails in 13 cases (38%). The thumb nails or great toe nails were affected in 25 of the 34 patients (73%). In 25 patients, histopathological features of acral lentiginous melanoma were found, with four cases of superficial spreading melanoma and five of nodular amelanotic melanoma. Of the latter group, four mimicked fibrous histiocytic tumour, and one was a desmoplastic malignant melanoma. The proportion of patients presenting with stage III disease decreased after 1982, with a corresponding increase in patients whose tumour thickness was less than 4 mm (stage II). Concurrently, the prognosis for subungual malignant melanoma improved. The 5-year survival rate in each of the periods 1969-82 and 1983-93 was 53 and 87%, respectively. This is similar to that found in plantar malignant melanoma and is felt to be due to a greater public awareness of the condition and to the introduction of effective chemotherapy (the DTIC-AC nitrosurea-vincristine (DAV) regimen). Although the frequency of malignant melanoma is rather low in the Japanese, our data indicate that there is a high incidence of subungual malignant melanoma. Public awareness of the early stage of malignant melanoma seems to have improved prognosis.

Newazaphilones named isochromophilones III~VI were isolated from the culture broth of Penicillium multicolor FO-3216 as inhibitors of acyl-CoA : cholesterol acyltransferase (ACAT). Their structures were elucidated by NMR and other spectroscopic analyses. The IC50 values of isochromophilones III, IV, V and VI for ACATactivity in an enzyme assay using rat liver microsomes were calculated to be 110, 50, 50 and 120fiM, respectively.

No abstract

Here we describe the application of the in vitro virus mRNA display method, which involves covalent linkage of an in vitro-synthesized antibody (phenotype) to its encoding mRNA (genotype) through puromycin, for in vitro evolution of single-chain Fv (scFv) antibody fragments. To establish the validity of this approach to directed antibody evolution, we used random mutagenesis by error-prone DNA shuffling and off-rate selection to improve the affinity of an anti-fluorescein scFv as a model system. After four rounds of selection of the library of mRNA-displayed scFv mutants, we obtained six different sequences encoding affinity-matured mutants with five consensus mutations. Kinetic analysis of the mutant scFvs revealed that the off-rates have been decreased by more than one order of magnitude and the dissociation constants were improved ∼30-fold. The antigen-specificity was not improved by affinity maturation, but remained similar to that of the wild type. Although the five consensus mutations of the high-affinity mutants were scattered over the scFv sequence, analysis by site-directed mutagenesis demonstrated that the critical mutations for improving affinity were the two that lay within the complementarity determining regions (CDRs). Thus, mRNA display is expected to be useful for rapid artificial evolution of high-affinity diagnostic and therapeutic antibodies by optimizing their CDRs.

Eight new components of terpendoles E to L were isolated and characterized from the culture broth of Albophomayamanashiensis using a different production medium. All the structures were elucidated by spectroscopic analyses including various NMRexperiments, indicating that all the terpendoles have the same indoloditerpene core as terpendoles A to D. Terpendoles J, K and L showed the moderate inhibition against acyl-CoA : cholesterol acyltransferase (ACAT)activity with IC50 values of 38.8, 38.0 and.32.4//m in rat liver microsomes, respectively. But terpendoles E~I showed weak activities (IC50 145~388 /iM).

No abstract

The prognosis of plantar melanoma has improved recently at our institute. The possible explanation for a trend to better survival in the second half period may be related to a decrease in stage IV disease as well as to an increase in the frequency of diagnosis of early stage disease.