Recurrent leg ulcers and arterial thrombosis in a 33-year-old homozygous variant of antithrombin.

We report here a homozygous variant case of antithrombin (AT) associated with arterial thrombosis and recurrent leg ulcers. The deep vein thrombosis was recognized by the venogram of his pelvic veins. His leg ulcers were scattered around his left ankle and accompanied by lipodermatosclerosis, which was evident in venous insufficiency. The propositus had developed cerebral infarction 12 years prior to his leg ulcers. Coagulation study showed low heparin cofactor activity of his AT with a normal level of immunoreactive AT. Nucleotide sequence analysis of the exon 2 of his AT gene showed Arg47-Cys mutation, leading to the lack of affinity of AT for heparin. The propositus is a homozygote for this abnormality.

[Yearly and seasonal fluctuation of PCB concentration in skin surface lipid].

PCB concentrations in the skin surface lipids of Yusho patients had been examined for 6 years (in July, 1990-1995). The concentrations in each patients showed a little fluctuation every year. It suggests that the cutaneous sebaceous system is one of the excretory systems of PCB. In 1995, measurement of PCB was performed also in October. The mean concentration of PCB was lower than that measured in Summer (692.7 ng/g in July versus 633.3 ng/g in October, p < 0.05). To explain the fluctuation, seasonal change of sebum composition should be examined.

[In vitro analysis for cellular toxicity of polychlorinated biphenys (PCBs) on HeLa cellular proliferation (IV)--the effect of Kanpo preparations on cellular toxicity].

In this study, we investigated the cell toxicity of polychlorinated biphenys (PCBs) as an indicator of the quantity of cellular protein in HeLa cells. Assay for protein concentration was performed by Lowry's method using a commercially available bovine serum albumin as standard preparation. The reductive action of inchinkou-tou, inchinkou, sansisi and daiou on the PCBs toxicity was investigated. The relationship of cell number (0-40.000) to protein concentrations (0-80 micrograms) was shown R2 = 0.993 (Y = 5.0 x 10(-6) X +0.027). The final concentration of these drugs and PCBs was used for 100 micrograms/ml, respectively. The cellar protein concentration increased to 20% with the addition of inchinkou-tou. Inchinkou and sansisi were revealed slightly elevation, but daiou was not. These results suggested that inchinkou-tou, kanpou preparation, was better effective than constructive crude drugs, but statistical evidence could not find.

The expression of placental-type glutathione S-transferase (GST-pi) in human cutaneous carcinoma in situ, that is, actinic keratosis and Bowen's disease, compared with normal human skin.

The expression of human placental type glutathione S-transferase (GST-pi) was investigated in human cutaneous carcinoma in situ, that is, actinic keratosis and Bowen's disease, and compared with that in normal skin, using Northern blot and immunohistochemical analysis. In Northern blot examination, the expression of GST-pi transcript was recognized in all instances. Carcinoma in situ showed significantly higher expressions of GST-pi than normal skin. In the immunohistochemical examination, nuclear staining of GST-pi was noticed in some dysplastic cells of carcinoma in situ, especially in Bowen's disease. In actinic keratosis, a framework appearance was noticed in the staining pattern at a lower magnification because the lower part of the cytoplasm of dysplastic cells lining the stratum basale was positive for GST-pi, and all cells of the stratum granulosum and more cells of the stratum spinosum showed stronger GST-pi positive reaction than normal skin. In Bowen's disease, GST-pi positive, dysplastic cells existed throughout the epidermis. Because GST-pi positive, dysplastic cells and GST-pi positive, normal looking squamous cells made the GST-pi positive cell nests throughout the epidermis, and GST-pi positive, dysplastic cells, and GST-pi negative, normal looking cells coexisted in the parabasal layer, they showed a sawtooth appearance in the staining pattern at a lower magnification. These findings suggest that GST-pi is involved in the process of carcinogenesis.

The expression of placental-type glutathione S-transferase (GST-pi) in human cutaneous squamous cell carcinoma and normal human skin.

The expression of human placental-type glutathione S-transferase (GST-pi) was investigated in human cutaneous squamous cell carcinoma (SCC) and normal skin using Northern blot and immunohistochemical analysis. In Northern blot examination, the expression of GST-pi transcript was recognized in all instances, and SCC showed a significantly higher expression of GST-pi than normal skin. In immunohistochemical examination, GST-pi was stained well in the cytoplasm of all cells of the stratum granulosum, many cells of the stratum spinosum and a few cells of the stratum basale in normal skin. Some cells of the stratum spinosum and almost all cells of the stratum basale showed only a weakly positive or almost negative reaction for GST-pi. No nuclear staining of GST-pi was obvious in normal epidermal cells. In SCC, many cells showed strong positivity for GST-pi in the cytoplasm, and some were obviously accompanied by nuclear staining of GST-pi. These findings suggest that GST-pi exists mainly in many cells in the upper layers of the normal epidermis and that GST-pi is involved in the process of carcinogenesis.

Chromosome abnormalities in skin fibroblasts probably induced by an anti-cancer drug.

Chromosome findings in cultured skin fibroblasts from a patient treated with an anti-cancer drug, pepleomycin sulfate, for his penis cancer are reported. In two batches of specimens (days 16 and 34, respectively), out of 120 cells examined, a total of 26 abnormal cells (21.7%) were found with no common chromosome abnormalities; there were no clones. This cytogenetic pattern of abnormalities without clones in cultured skin fibroblasts differs from that seen in congenital disease or radiation-exposed skin fibroblasts. It is suggested that the anti-cancer agent is the most likely etiological factor for these uncloned chromosome abnormalities in cultured skin fibroblasts.

[Correlation between electron microscopic nuclear irregularity index and malignancy of epidermal tumors].

Quantitative electron microscopy was used to measure nuclear contours of epidermal tumors. The degree of nuclear indentation in the epidermal cells, expressed as the nuclear irregularity index (NII), was calculated on electron micrographs by measuring the nuclear profile circumference and nuclear area. In all, 3,297 nuclei photographed from healthy skin specimens, seborrheic verruca, actinic keratosis (AK), keratoacanthoma (KA) and squamous cell carcinoma (SCC) were measured. Numbers and frequencies of special nuclei, which consisted of 2 nuclei or more and which had intranuclear cytoplasm, were also calculated. Significant differences were found between mean NII for SCC (1.376 +/- 0.258) and for healthy skin (1.236 +/- 0.152). In SCC, group mean NIIs for histologically high grade malignant cases and for recurrent and/or metastatic cases were higher than those of lower grade malignant cases and non recurrent metastatic cases. These findings suggest that NII can be regarded as a significant and objective marker for deciding the grade of malignancy and prognosis in SCC. KA also showed a high mean NII (1.328 +/- 0.215), but the frequency and types of special nuclei were different from those of SCC. In AK, the frequency of special nuclei was much higher than healthy skin, although no significant differences were found in mean NII.