Photoprovocation test and immunohistochemical analysis of inducible nitric oxide synthase expression in patients with Sjögren's syndrome associated with photosensitivity.

BACKGROUND: Annular erythema (AE) in Sjögren's syndrome (SS) usually develops on areas of sun-exposed skin and is exacerbated during summer. OBJECTIVES: To evaluate photosensitivity in SS and to investigate the involvement of ultraviolet (UV) radiation in the development of AE in SS. METHODS: Phototesting with UVA and UVB was performed on 14 SS patients, including 10 with primary SS. Clinical and histological features as well as expression of inducible nitric oxide synthase (iNOS) in the evoked skin lesions were compared with those of lupus erythematosus (LE). Eleven SS patients had a history of photosensitive AE (n = 4), papules (n = 3) or other types (n = 4) of lesions on their sun-exposed skin that were induced or aggravated by sunlight exposure. RESULTS: Phototesting induced a prolonged erythematous response (n = 8), infiltrated erythema (IE) (n = 4) and/or papules (n = 3) in 11 of 14 SS patients, including one with primary SS without a history of photosensitivity. Histologically, the induced IE and papules showed coat-sleeve-like or sparse perivascular infiltration of lymphocytes similar to that in primary skin lesions of AE in SS. No epidermal changes characteristic for LE were found except for partial and mild liquefaction degeneration in three cases. In contrast, two cases were indistinguishable from the papular type of polymorphic light eruption in several aspects, including their primary skin lesions and early response to a photoprovocation test. Immunohistochemistry revealed diffuse expression of iNOS throughout the epidermis, which is characteristic for LE, in the three SS patients with minimal liquefaction degeneration, while the remaining seven SS patients examined exhibited no iNOS staining or a normal expression pattern. CONCLUSIONS: Our results indicate that photosensitivity exists in certain primary SS patients, and that UV is critical to the development of AE in SS, probably through a pathological mechanism distinct from that in LE.

Porphyria cutanea tarda and hepatitis C virus infection.

We studied the prevalence of hepatitis C virus (HCV) infection in 20 Japanese patients with sporadic-type porphyria cutanea tarda (PCT). Seventeen of the 20 patients (85%) had anti-HCV antibodies. Biochemical remission was observed in nine patients, six of whom still had positive HCV RNA copies. These results suggest that HCV infection is a triggering factor for PCT in Japan. However, continuous HCV infection seems to exert little influence on the maintenance of abnormal porphyrin metabolism. Hepatocellular carcinoma (HCC) developed in five of the 17 HCV-positive patients, three of whose PCT was in remission. Four of these patients showed chronic active hepatitis or cirrhosis on liver biopsy. PCT patients with HCV infection should be followed up long-term because of the possibility of HCC. To evaluate the risk of HCC, liver biopsy may be required, even when the patient is in biochemical remission.

[A case of folie à trois].

We examined a case of a family of induced insanity (folie à trois) which is characterized by its delusion of jealousy, and reported about the establishment and disappearance process of the delusion. We examined the background of the fact that the family members shared the same delusion and the family dynamics. We concluded that induced insanity is an extended expression of family illness which appears in the process in which the family expresses its problematic theme and tries to cope with it.

[Scleroderma and porphyria cutanea tarda].

Examination was made of sclerodermoid changes in porphyria cutanea tarda (PCT) and PCT in association with true scleroderma. Although sclerodermoid change in PCT is rare in Japan, it is important in the diagnosis of PCT when there are few other clinical signs characteristic of PCT. In the present case, slight improvement in cutaneous sclerosis was noted following treatment for PCT, but pulmonary changes somewhat intensified. The reason for the association of PCT with progressive systemic sclerosis (PSS) remains obscure. Elevated uroporphyrin due to PCT may possibly increase cutaneous sclerosis in PSS. A diagnosis of PCT should be considered for patients presenting scleroderma, since it is difficult to distinguish sclerodermoid changes from true scleroderma.

[In vitro analysis for cellular toxicity of polychlorinated biphenyls(PCBs) and 2, 3, 4, 7, 8-pentachlorodibenzofuran (PCDF) on HeLa cell proliferation(III)--the effect of cytoactivator and antilipemic agents on cell toxicity].

We investigated the cell toxicity of polychlorinated biphenyls (PCBs) and 2, 3, 4, 7, 8-pentachlorodibenzofuran (PCDF) as indicators of the optical density (280nm) which is total protein in HeLa cells. Furthermore, the reductive action of cytoactivator and antilipemic agents on the PCBs and PCDF toxicity were evaluated. The quantity of total cellular protein increased to 20% with the addition of sodium dextran sulfate (2.5%) at the presence of PCBs, and 25% in the case of PCDF. However, the slope of the curve of cell proliferation of HeLa cells at the presence of PCBs or PCDF became to overlap with a control group at the presence of any other drugs except for sodium dextran sulfate. These results mean that PCBs and PCDF cell toxicity were suppressed a little by sodium dextran sulfate, but the case of other cytoactivator and antilipemic agents did not.

[Polychlorinated biphenyls (PCBs) and polychlorinated quaterphenyls (PCQs) concentrations in skin surface lipids and blood of patients with Yusho].

The relationship between Polychlorinated Biphenyls (PCBs), and Polychlorinated Quaterphenyls (PCQs) concentrations in the skin surface lipids and blood was investigated in twenty two patients with PCB poisoning (Yusho) and 9 control subjects were analyzed. The collection of skin surface lipids was performed by the method of cotton pad with 70% ethyl alcohol. The alkaline decomposition method described as "the official standard analytical methods for the isolation of PCBs and PCQs fractions" was used. In the blood of control group, the mean value of PCBs concentration was 1.8 ng/g, and that of PCQs concentration was very low and undetectable by our analytical method. On the other hand, the PCBs concentration in the Yusho group was three times higher than those in the control group. The mean value of PCQs concentration was 1.90 ng/g in Yusho group, while it was not detectable in the control group. In the skin surface lipids of patients with Yusho, the mean value of PCBs concentration was 668.6 ng/g, but was 256.7 ng/g in the control group. The mean value of PCQs concentration in the skin surface lipids of Yusho patients was 35.4 ng/g, although it was not detected in the control group. These values of the skin surface lipids in 1993 were decreased as compared with those in 1992. PCBs and PCQs levels in the skin surface lipids were higher than those in the blood. These findings suggests that cutaneous sebaceous system is one of the excretory systems of polyhalogenated chemicals, such as PCBs or PCQs, when these chemicals are precipitated in human or mammalian.

[Effects of polychlorinated biphenyls (PCBs) on porphyrin metabolism--experimental porphyria induced by large single doses of PCBs].

The effects of large single doses of PCBs and iron overload on porphyrin metabolism were investigated in male C57BL/6 mice. A single intraperitoneal dose of Kanechlor-500 (10 mg/mouse) caused urinary uroporphyrin to increase three days after injection. This increase was transient without porphyrin accumulation in the liver. Iron overload (12.5 mg/mouse) showed a tendency to prolong the action of PCBs.

Relationship between porphyria cutanea tarda (PCT) and viral hepatitis.

Recent reports have revealed the high prevalence of serological markers of viral hepatitis in porphyria cutanea tarda (PCT). We present two cases of PCT associated with hepatitis C and discuss the relationship between PCT and viral hepatitis. Case 1: A 50-year-old Japanese male noticed blisters, erosions, and fragility on sun-exposed areas of his skin in November of 1990. He had no history of excessive alcohol intake. He had been taking analgesics for eighteen years. Case 2: A 64-year-old Japanese male was referred in October of 1989 because of pigmentation on sun-exposed areas of his skin. He had been drinking alcohol excessively for 43 years. The hepatitis C virus (HCV) antibody was present in each case. Tests for the HCV antibody and hepatitis B serological markers were run in 5 other patients. HCV antibody was present in 3 of them. The two cases negative for the HCV antibody exhibited the hepatitis B antibody. We speculated that viral hepatitis infection may play an important role in precipitating PCT in cases with a history of a long term excessive intake of alcohol or chemicals.

Polychlorinated biphenyls (PCBs) and polychlorinated quaterphenyls (PCQs) concentrations in skin surface lipids and blood of patients with yusho.

The relationship between PCBs and PCQs concentrations in the skin surface lipids and blood was investigated in this study. PCBs and PCQs concentrations in thirty two patients with PCB poisoning (Yusho) and 20 normal controls were analyzed. The collection of skin surface lipids was performed by the method of cotton pad with 70% ethyl alcohol. The alkaline decomposition method described in the official standard analytical methods for the isolation of PCBs and PCQs fractions was used. In the blood of control group, mean value of PCBs concentration was 2.1 ng/g, and that of PCQs concentration was too low to be detected by our analytical method. On the other hand, the PCBs concentration in the Yusho group were two times higher than those in the control group. The mean value of PCQs concentration was 0.90 ng/g in Yusho group, while it was not detectable in the control group. In the skin surface lipids of patients with Yusho, the mean value of PCBs concentration was 580.0 ng/g, but was 324.4 ng/g in the control group. The mean value of PCQs concentration in the skin surface lipids of Yusho patients was 25.7 ng/g, although it was not detected in the control group. PCBs and PCQs levels in the skin surface lipids were higher than those in the blood. This means that cutaneous sebaceous system is one of the excreted systems of polyhalogenated chemicals, such as PCBs or PCQs, when these chemicals are precipitated in human or mammalians.

The synergistic effect of chlorinated chemicals and low concentration of griseofulvin on porphyrin metabolism--the effect of 0.05% hexachlorobenzene and 0.1% griseofulvin on young and old mice.

The difference in the synergistic effect of 0.05% hexachlorobenzene (HCB) and 0.1% Griseofulvin (GF) on porphyrin metabolism between young (4 weeks old) and old (8 weeks old) mice was investigated. These mice were divided into four groups, group A was treated with feeds containing 0.05% HCB and 0.1% GF, group B with 0.05% HCB, group C with 0.1% GF and group D with normal feed. The treatments were continued for 8 and 16 days, after which porphyrins in the erythrocytes, feces and liver were analyzed by a chromatographic method. Hepatic protoporphyrin levels had risen by 8th day in the young mice treated with 0.05% HCB and 0.1% GF, and by 16th day in the young mice treated with 0.1% GF, but no rise in the hepatic protoporphyrin levels in the old mice was seen. Hepatic protoporphyrin level by 16th day in the young mice treated with 0.1% GF had significantly risen compared to that in the old mice with same treatment. Fecal coproporphyrin level had risen at 8th day in the young mice treated with 0.05% HCB and 0.1% GF and by 16th day in the young mice treated with 0.05% HCB. It had also risen by 16th day in the old mice treated with 0.05% HCB and 0.1% GF. Fecal protoporphyrin level in the young mice treated with 0.05% HCB and 0.1% GF, 0.1% GF alone was three to four times higher than those in normal mice. Erythrocytic coproporphyrin and protoporphyrin levels in the young mice treated with 0.05% HCB and 0.1% GF, 0.05% HCB or 0.1% GF alone were generally higher than those in the old mice.(ABSTRACT TRUNCATED AT 250 WORDS)

[The influence of ursodesoxycholic acid (URSO) on griseofulvin (GF)-induced protoporphyria].

To investigate the influence of ursodesoxycholic acid (URSO) on griseofulvin (GF)-induced protoporphyria mice, analysis of hepatic, erythrocytic, and fecal porphyrin levels and histopathological examinations were performed in dd-Y strain mice treated with 0.5% GF and/or 0.5% URSO. We observed no difference of hepatic and fecal porphyrin levels between the GF group and GF with URSO group, although an elevation of erythrocytic porphyrin levels was seen in the GF with URSO group. However, remarkable hepatic atrophy revealed in the GF with URSO group. Furthermore, a strong emission of red fluorescence was observed in the liver under long wave ultraviolet. Histopathologically, many focal necrosis was found in the liver specimen treated with GF and URSO. We expected that URSO might facilitate the excretion of porphyrin from bile to feces because of suppression of transfer from serum to erythrocyte like cholic acid (CA). But, the action of URSO appears to be different from that of CA. We consider that the 0.5% concentration of URSO plays a role in the cytotoxic effect to the liver.

The synergistic effect of chlorinated chemicals (trichlorosalicylanilid, 4-chloro-m-cresol, trichlorophenoxyacetic acid, trichloroethanol, trichloromethiazide, trichlorofon and trichloroacetaldehyde) and low concentrations of griseofulvin on porphyrin metabolism.

The synergistic effect of chlorinated chemicals and 0.1% griseofulvin (GF) on porphyrin metabolism was investigated. Drinking water containing 0.03% trichlorosalicylanilid, 0.1% 4-chloro-m-cresol, 0.1% trichlorophenoxyacetic acid, 0.3% trichloroethanol, 0.1% trichloromethiazide, 0.3% trichlorofon and 0.1% trichloroacetaldehyde was given separately to dd-y strain mice. Each group was divided into two subgroups, one treated with feed containing 0.1% GF and the other treated with normal feed. The treatments were continued for 45 to 165 days, after which porphyrins in the erythrocytes, feces and liver were analyzed by a chromatographic method. In the 0.03% trichlorosalicylanilid and 0.1% GF group, 0.1% 4-chloro-m-cresol and 0.1% GF group, 0.1% trichlorophenoxyacetic acid and 0.1% GF group and 0.3% trichloroethanol and 0.1% GF group, a slight elevation of fecal coproporphyrin and protoporphyrin was seen. There was no elevation of hepatic and erythrocytic porphyrins. This result shows that the chemicals used in this study did not have a potential for porphyria, but that they are capable of inducing slight porphyrin abnormalities in a synergistic reaction with 0.1% GF.

A comparative study on the concentrations of polychlorinated biphenyls (PCBs) and polychlorinated quaterphenyls (PCQs) in the blood and hair of "Yusho" patients and inhabitants of Nagasaki Prefecture.

The relationship between polychlorinated biphenyl (PCB) and polychlorinated quaterphenyl (PCQ) concentrations in the blood and hair was investigated. The materials in this study consisted of 49 blood samples and hair obtained from 27 patients with PCB poisoning (Yusho) and 22 normal controls. The alkaline decomposition method described in the official standard analytical methods for the isolation of PCB and PCQ fractions was used. In the blood of the control group, the mean concentration of PCBs was 2.25 ppb, while the concentration of PCQs was too low to be detected by our analytical method. On the other hand, the mean concentration of PCBs in the Yusho group was about 2.8 times higher than that in the control group. The mean concentration of PCQs in the blood was 0.61 ppb in the Yusho group, but PCQs were not detectable in the control group. In the hair, the mean concentration of PCBs was 25.85 ppb and 9.41 ppb in the Yusho group and control group respectively. The mean concentration of PCQs in the hair of Yusho patients was 0.44 ppb, but PCQs were not detected in the control group. The PCB level in the hair was higher than that in the blood, but the PCQ level in the hair was lower than that in the blood. These results suggest a difference of excretory system among polyhalogenated compounds such as PCBs or PCQs. We consider that PCBs display a greater affinity than PCQs for the pilosebaceous system of the human skin.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of chlorinated chemicals on porphyrin metabolism--the synergistic effect with chlorinated chemicals and low concentrations of griseofulvin.

The synergistic effect of chlorinated chemicals and 0.1% griseofulvin on porphyrin metabolism was investigated. Feeds containing 0.1% 4-chloro-m-cresol, 0.1% cumarone or 0.25% trichloroacetic acid with or without 0.1% griseofulvin were given to dd-y strain mice respectively. The treatments were continued for 10 to 450 days, after which coproporphyrin and protoporphyrin in the erythrocytes and liver were analyzed. In the 0.1% griseofulvin alone group, protoporphyria was induced in 6 of 55 dd-y strain mice, although the other 49 mice did not show any abnormal porphyrin metabolism and the severity of the protoporphyria was mild in the 6 mice. In the 4-chloro-m-cresol group, a slight elevation of erythrocytic porphyrins was seen, but the difference was not statistically significant. Elevation of the hepatic porphyrins was not seen. Trichloroacetic acid and cumarone did not influence porphyrin metabolism, and also there was no synergistic effect of griseofulvin on porphyrinopathy. These results suggest that the three chemicals selected in this study are not capable of inducing porphyrinopathy.

A comparative study on polychlorinated biphenyls (PCB) and polychlorinated quaterphenyls (PCQ) concentrations in subcutaneous fat tissue, blood and hair of patients with yusho and normal control in Nagasaki prefecture.

The relationship between PCB and PCQ concentrations in the blood, subcutaneous fat tissue and hair was investigated in this study. PCB and PCQ concentrations in twenty four patients with PCB poisoning (yusho) and 59 normal controls were analyzed. The alkaline decomposition method described in the official standard analytical methods for the isolation of PCB and PCQ fractions was used. The mean value of PCB concentrations was 2.43 ppb, CB% ratio was 0.69 and the PCQ concentration in the blood of the control group was too low to be detected by our analysis. On the other hand, the PCB concentration and CB% ratio in the yusho group were two times higher than those in the control group. The mean value of PCQ concentration was 1.34 ppb in the yusho group although it was below the level of detection in the control group. The mean PCB concentration in the hair of patients with yusho was 28.92 ppb, and 8.06 ppb in the control group. CB% ratio in the hair of patients with yusho was two times higher than that in the control group. The mean value of PCQ concentration in the hair of patients with yusho was 0.55 ppb although it was not detected in the control group. The PCB and PCQ concentrations in the hair were not greatly elevated when compared with those in the subcutaneous fat tissue. However, the hair is an excellent sample for the detection of these chemicals because it can be collected simply without operation.

Regional differences of PCB and PCQ concentrations in the blood and subcutaneous fat tissue of residents of Nagasaki.

In this study, we analyzed PCB and PCQ concentrations in the subcutaneous fat tissue of residents of Nagasaki Prefecture, and compared these levels between the blood and subcutaneous fat tissue of people living in various parts of the prefecture. Seventy-one inhabitants were examined. In the blood, PCB concentrations in Tamanoura and Fukue were significantly higher than those in Nagasaki City. The CB% ratio in Tamanoura was significantly higher than that in Nagasaki and Isahaya. PCQ concentrations were below detection level except in one case. PCB concentrations in fishery areas showed higher levels than urban or agricultural areas. PCB concentration in the subcutaneous fat tissue was 100 times higher than that in the blood. PCQs could be detected in almost all of the subcutaneous tissues, but there was no regional difference in the PCQ concentration.

Idiopathic calcinosis of the scrotum presenting as a solitary pedunculated tumour.

Idiopathic calcinosis of the scrotum usually develops in the form of scrotal calcified nodules varying in number from 1 to over 100 and from pinhead to walnut in size. In this paper, we describe a case of this skin disorder which had developed as a solitary pedunculated tumour. To the best of our knowledge, no such patient has been previously described.