Masaaki Morohashi

Emergence of resistance to acyclovir and penciclovir in varicella-zoster virus and genetic analysis of acyclovir-resistant variants.

We have characterized the differential actions of acyclovir and penciclovir against varicella-zoster virus (VZV) in cell culture by comparing the frequency of appearance of resistant viruses followed by their characterization. Cells were infected with cell-free virus and the cultures were successively treated with increasing concentrations of acyclovir or penciclovir. Drug-resistant viruses were selected in the presence of 6 microg/ml of acyclovir or penciclovir. The emergence frequency of resistant viruses was significantly higher following acyclovir exposure than following penciclovir exposure (Fishers exact test, P<0.0001), possibly reflecting virus growth differences under these experimental conditions. Based on antiviral drug susceptibility and thymidine kinase (TK) activity assays, 11 acyclovir-resistant variants from seven experiments using three virus strains (Kawaguchi strain, Oka varicella vaccine strain and a clinical isolate from a zoster patient) were found to be TK-deficient. Sequence analysis of TK-deficient variants of the Kawaguchi strain revealed deletions that caused frameshifts, resulting in premature termination in the TK gene.

Suppression of recurrent genital herpes simplex virus type 2 infection by Rhus javanica in guinea pigs

Rhus javanica has been shown to exhibit anti-herpes simplex virus (HSV) activity and potentiate the anti-HSV activity of acyclovir in vitro and in vivo. This extract was examined for its suppressive efficacy on recurrent genital infection in guinea pigs. Guinea pigs were primarily infected intravaginally with HSV type 2 (HSV-2). Prophylactic oral administration, at the dose corresponding to human use, of R. javanica significantly reduced the incidence, severity and/or frequency of spontaneous and severe skin lesions as compared with latently infected guinea pigs administered with water. This prophylactic efficacy was confirmed by the crossover administration, for more than 2 months, of R. javanica and water to the infected guinea pigs. Toxicity, such as weight loss, from R. javanica administration was not observed in the guinea pigs. When recurrent HSV-2 disease was induced by ultraviolet irradiation 3 months after primary infection, the prophylaxis with R. javanica was also significantly effective in reducing the severity of ultraviolet-induced skin lesions. Thus, prophylaxis of recurrent genital HSV-2 infection with R. javanica may preserve the efficacy of acyclovir by reducing both the use of acyclovir and the appearance of acyclovir-resistant viruses.

Effect of some alkaloids, flavonoids and triterpenoids, contents of Japanese-Chinese traditional herbal medicines, on the lipogenesis of sebaceous glands.

The effects of some alkaloids and flavonoids, which are major ingredients in some of the Japanese Kampoh drugs (Japanese-Chinese traditional herbal medicines) experientially known to be efficacious for the treatment of acne vulgaris, on the lipogenesis in the sebaceous glands of the hamster ear, an excellent animal model for the human sebaceous gland, were studied. Lipogenesis was assayed by determining 14C incorporation into sebaceous lipids extracted from the sebaceous glands which were preincubated with 14C-acetate. We found that the lipogenesis in the hamster sebaceous glands was suppressed 63 and 54% by 10(-4) M berberine (an alkaloid) and wogonin (a flavonoid), respectively. We suggest that the therapeutic effects of some Japanese Kampoh drugs experimentally used for acne vulgaris could be due to inhibition of lipogenesis by their active ingredients such as berberine and wogonin.

Immunohistochemical Study of Langerhans Cells in Skin Tumors

The behavior of Langerhans cells in skin tumors was investigated by immunohistochemical techniques using OKT6. OKT6-positive cells were numerous in squamous cell carcinomas, seborrheic keratoses and keratoacanthomas. They were rare in basal cell carcinomas, Bowens disease, eccrine poromas, extramammary Pagets disease and warts. In solar keratosis, the number of OKT6-positive cells was almost equal or slightly larger compared to the normal epidermis. These results indicate that the density of Langerhans cells may not correlate with the degree of malignancy but, to a certain extent, with the nature of the membrane of tumor cells occurring e.g. during keratinization.

Effects of azelastin on pruritus and plasma histamine levels in hemodialysis patients.

Background. Persistent pruritus is the most common symptom in hemodialysis patients. Its causes are poorly understood and there is no effective treatment. We have studied the effect of azelastin HCL on the plasma histamine concentrations and pruritus in maintenance dialysis patients with or without erythropoietin therapy.

HIDROACANTHOMA SIMPLEX: AN ULTRASTRUCTURAL STUDY AND COMPARISON WITH ECCRINE POROMA

Hidroacanthoma simplex is a rare tumor and its histogenesis and classification have been the subject of discussion, especially as to its relation to eccrine poroma. The tumor in this study developed on the knee of an old woman as a Bowens disease‐like lesion. Clinical and histological examinations confirmed the diagnosis of hidroacanthoma simplex.

Cutaneous Metastasis of Renal Cell Carcinoma: An Electron Microscopic Study

A case of cutaneous metastasis of renal cell carcinoma in a 67‐year‐old man is described. Right side nephrectomy had been performed three years earlier, and a renal cell carcinoma was diagnosed. Following a bruise, the patient noticed an erythematous nodule on the scalp. Histological examination of this skin lesion showed atypical tumor cells consisting predominantly of clear cells with a honeycomb‐like or adenoid structure. Electron microscopic examination revealed that the tumor cells were divided into three groups: clear cells with abundant glycogen, dark cells with abundant mitochondria, and intermediate cells containing both glycogen and mitochondria in varying proportions. Some of the tumor cells with an adenoid pattern had a brush border‐like structure in the lumen. These results support the diagnosis of metastatic renal cell carcinoma. An electron microscopic approach may aid in diagnosis of cutaneous metastasis from renal cell carcinoma.

A case of erythromelanosis follicularis faciei with a unique distribution.

A 16‐year‐old Japanese boy with erythromelanosis follicularis faciei (EFF) with an unusual distribution is described. The clinical features of classic EFF consist of reddish‐brown discoloration of the skin with fine follicular hyperkeratosis in the preauricular areas, and occasionally on the temples and the lateral aspects of the neck. The present case is unique in that similar lesions also occurred on the auricles and eyebrows. Both light and electron microscopic findings of the lesions were consistent with the diagnosis of EFF.

ULTRASTRUCTURE OF INCONTINENTIA PIGMENTI ACHROMIANS, WITH SPECIAL REFERENCE TO MELANOCYTES AND NERVE ENDINGS

Studies of a new Japanese case of incontinentia pigmenti achromians were made by electron microscopy.

Nevus cells observed in the sebaceous glands.

Of sebaceous gland‐containing specimens of melanocytic nevi, a total of 79 specimens from 70 cases of nevocellular nevus (consisting of 10 cases of compound nevus and 60 of intradermal nevus), four cases of juvenile melanoma and three of blue nevus were examined light‐microscopically in detail for the presence or absence of nevus cells or dermal melanocytes in the sebaceous glands. As a result, clusters of cells that appeared to be nevus cells were found in the sebaceous glands of specimens from a total of three cases, that is, two cases of nevocellular nevus i.e. compound nevus, and one of the cases of juvenile melanoma. Two cases were infantile and one case was the age of puberty. The origin of the nevus cells found in the sebaceous glands is discussed.