Fumio Murayama

Effects of KC-400 (polychlorinated biphenyls) on porphyrin metabolism--liver and blood porphyrin analyses in rats treated with KC-400.

To investigate the influence of polychlorinated biphenyls (PCB) on porphyrin metabolism, Wistar rats were orally administered KC‐400. The mean value of liver/body weight ratio in normal rats was 3.86%, with a range of 3.44% to 5.22%. Their mean blood protoporphyrin level was 23.3 μg/dl packed cell volume (p.c.v.), with a range of 11.8 to 64.4 μg/dl p.c.v., and their mean liver protoporphyrin level was 0.17 μg/gm wet weight, with a range of 0.03 to 0.40 μg/gm wet weight.

A BIOCHEMICAL STUDY OF EXPERIMENTAL PORPHYRIA: I. THE INFLUENCE OF GRISEOFULVIN AT VARIOUS CONCENTRATIONS ON PORPHYRIN METABOLISM

In order to determine the lowest concentration of griseofulvin (GF) needed to induce abnormal porphyrin metabolism, D‐D strain mice were fed with a feed containing GF in concentrations of 0.1%, 0.5%, and 1.0%. The liver and blood porphyrin levels were analyzed, and the red fluorescence of the liver and blood observed with a fluorescent microscope. In the 0.5% GF and 1.0% GF groups, a swelling of the liver was observed, and coproporphyrin and protoporphyrin levels in the liver and the blood increased markedly. However, the increase in protoporphyrin levels was more prominent than the increase of coproporphyrin levels. The increase in the liver protoporphyrin was more marked than that in the blood porphyrin. Comparisons of the 0.5% GF and 1.0% GF groups revealed that liver swelling was more prominent in the 1.0% GF group. A high degree of metabolic abnormality in blood protoporphyrin was found in 1.0% GF animals whose feeding period was rather short. In the 0.1% GF group, liver swelling was hardly noticeable, and there were no differences between the short feeding and long feeding groups. Although no abnormalities in blood porphyrins were noticed in comparison with the normal group, abnormally high levels of liver porphyrins were found in 3 out of the 34 treated mice. No differences from the normal group were noted in the remaining 31 animals. In the 0.5% GF and 1.0% GF groups, red fluorescence of the liver was seen in all cases, while in the 0.1% GF group, reticular red fluorescence was noted in only one animal.

THE USE OF A METAL HALIDE LAMP FOR THE INDUCTION OF PHOTOHEMOLYSIS IN PORPHYRIA

Several light sources, including sunlight, xenon lamps, fluorescent lamps, mercury lamps and carbon arc lamps, have been used to provoke skin changes for phototests in patients with porphyrias, or to induce experimental hemolysis of porphyrins for research. The metal halide lamp has a strong emission range between 400 nm and 450 nm, and a relatively low emission range in the ultraviolet region. For this reason, we explored the possibility that this lamp could be used to induce photohemolysis caused by hematoporphyrin (HP) and the radiation of light. Twenty to forty μg of HP‐HCl was added to 25 ml of a normal red blood cell suspension. The flask containing this red blood cell suspension was then irradiated using a metal halide lamp with 3.6 to 10.8 J/cm2 of light. All of the irradiated red blood cell suspension was hemolyzed, but the non‐irradiated control showed very little hemolysis.

Mechanism of Blister Formation in Porphyria Cutanea Tarda: I. Histopathological Observation of Blisters in Three Cases of Porphyria Cutanea Tarda

We performed a histopathological investigation of the bullous lesions in 3 cases of porphyria cutanea tarda. All cases showed subepidermal bullae by light microscopy. PAS positive materials were present on the roof of the bullae and partially present on their bases. Electron‐microscopically, the basal lamina was clearly recognized on the base. From these results, we suggest that the blister in porphyria cutanea tarda occurs initially within the junctional zone; this initial bulla may quickly change into a dermolytic bulla with additional stimulation.

Biochemical studies of experimental porphyria. II. The influence of porphyrinogenic substances in mice treated with low concentrations of griseofulvin.

Our previous study showed that a 0.1% concentration of griseofulvin (GF) in feed induced an abnormality of porphyrin metabolism in some dd‐K strain mice. To investigate the kind of changes in porphyrin metabolism that would be produced by other chemicals compared to the administration of 0.1% GF alone, estrogen, ethyl alcohol‐iron mixture and PCB was given to dd‐K strain mice. The numbers of mice with high liver protoporphyrin levels were increased in the group treated with both 0.1% GF and ethyl alcohol‐iron mixture, in comparison to the levels in the 0,1% GF alone and the ethyl alcohol‐iron mixture alone groups. A slight elevation in the liver protoporphyrin level was noted in only one mouse of the ethyl alcohol‐iron mixture group. The remaining mice showed normal levels. From this finding, it was presumed that the administration of ethyl alcohol‐iron mixture has the potential to intensify the activity of 0.1% GF alone. An elevation of the liver coproporphyrin and protoporphyrin levels was seen in the group treated with both 0.1 % GF and estrogen, as compared to the 0.1% GF alone and the estrogen alone groups. In those treated with estrogen alone, liver porphyrin levels were within normal limits except for one mouse, which showed an increase of liver protoporphyrin. An elevation of liver coproporphyrin and protoporphyrin was seen in 8 of 12 mice treated with both PCB and 0.1% GF, while there was no change in the PCB alone group. From these findings, it was inferred that the mechanism of abnormal porphyrin metabolism due to estrogen and PCB combined with 0.1% GF differs from the mechanism of abnormality due to 0.1% GF alone. It appears that the addition of some chemicals to a 0.1% GF feed enhances the action of the 0.1% GF alone.

URINARY PORPHYRIN ANALYSES IN PATIENTS WITH PORPHYRIA CUTANEA TARDA

Urinary porphyrin analyses were carried out in five patients with porphyria cutanea tarda and in a control group of 44 individuals. Quantitative analysis revealed that the mean value of coproporphyrin was 67.3 μg/l (range 13.1–189.1 μg/l) in 44 normal individuals and the mean value of uroporphyrin was 9.7 μg/l (range 5.0 to 13.7 μg/l) in 11 of 44 controls, but not detectable in the remainder. Four of the five patients with porphyria cutanea tarda, however, had markedly elevated coproporphyrin and uroporphyrin levels. Urinary porphyrin pattern analysis was carried out using one dimentional thin layer chromatography. The pattern in controls revealed that the mean value of coproporphyrin was 85.5%, while the other fractions consituted less than 6.0%. In the porphyria cutanea tarda group, however, hepta‐carboxyl porphyrin and uroporphyrin were predominant in two; all five fractions appeared in roughly equal amounts in one; and in the remaining two, coproporphyrin was decreased to a value of only about 50%.

Seven cases of porphyria cutanea tarda.

Porphyria cutanea tardaの7例を報告した。全例男子例で, 年令的には47才から69才であつた。7例中6例はアルコール摂取歴が認められたが, 症例4の1例のみはアルコール摂取について不明確であつた。患者は5人が長崎県在住, 2例は佐賀県在住であつた。皮膚所見では7例すべてに, 色素沈着, 瘢痕, 糜爛, 皮膚の脆弱などがみられ, そのほか2例に多毛, 2例に稗粒腫が認められた。光線過敏状態は2例に認められ, 日光曝露による皮疹の増悪に患者自身が気づいていた。ポルフィリン体測定値では, 7例中6例は尿中ポルフィリン体排泄量が500μg/L以上でUP優勢の排泄像を示していた。しかし, 1例は200μg/L以下の排泄量であつたが, UP優勢像であつた。糞便ポルフィリン体では, 6例中3例は100μg/g dry weight以上の排泄量を示し, かつCP優勢像を示していた。また2例は50∼100μg/g dry weightの排泄量であつたが, 1例はCP優勢, 1例はPP優勢像を示していた。1例は50μg/g dry weight以下の排泄量であつたが, CP優勢であつた。血液ポルフィリン体は6例とも正常域内であつた。生化学的所見では, 血清鉄は7例中2例が200μg/dl以上の高値を示したにすぎなかつた。肝機能検査では, 全例になんらかの異常値を認めたが, いずれも軽度の異常にとどまつていた。免疫グロブリン値では測定した5例中2例に2,000mg/dl以上のIgG値の上昇をみた。

Biochemical Study of Fecal Porphyrin in Porphyria Cutanea Tarda

Fecal, urinary and erythrocyte porphyrin analyses using the solvent extraction method were performed in 26 patients with porphyria cutanea tarda (PCT) and 144 normal controls. The levels of fecal uroporphyrin (UP) and coproporphyrin (CP) were markedly increased in the PCT group, especially in comparison with the protoporphyrin (PP) level. The values of the UP/PP and CP/PP ratios in the feces were also elevated over those in the control group. It appears that fecal porphyrin excretion is basically similar to urinary porphyrin excretion in PCT. The analysis of fecal porphyrins and the observation of fecal UP/PP and CP/PP ratios may be helpful in the biochemical diagnosis of PCT. In particular, the elevation of CP/PP ratio is characteristic of PCT.

Five Cases of Porphyria Cutanea Tarda with Mild Cutaneous Changes: Evaluation of the Efficacy of Phlebotomy by the Pattern Analysis of Urinary Porphyrins

Five cases of porphyria cutanea tarda (PCT) with mild cutaneous changes are reported. Acute episodes of photosensitivity were not seen in all patients. Laboratory examinations showed a predominance of uroporphyrin (UP) excretion in the urine in 4 out of 5 cases. One case showed a relatively low urinary porphyrin level even though abnormality of the porphyrin pattern was present. Four cases showing a predominance of UP excretion in the urine revealed a high level of serum coproporphyrin (CP) as well. Histopathologically, all cases showed a deposition of PAS positive materials surrounding the small blood vessels in the upper dermis, in addition to the deposition of IgG materials visualized by the immunofluorescent technique.

PCB and PCQ concentrations in subcutaneous tissue from patients with PCB poisoning (yusho).

Polychlorinated biphenyl (PCB) and polychlorinated quaterphenyl (PCQ) concentrations in the blood and subcutaneous fat tissue from 11 patients with PCB poisoning (Yusho) and 10 controls were analyzed by electron captured gaschromatography. The mean concentration levels of blood PCB and PCQ and the CB% ratio were elevated in patients with Yusho. The PCB pattern was the A type in 5 cases and the B type in 6 others. The mean concentration level of PCB in subcutaneous fat tissue was 1579.45 ppb in the Yusho group, 3.9 times higher than that in the control group. The mean concentration level of PCQ was 206.65 ppb, 119 times higher than that in the control group. The mean value of CB% was 3.22 in the Yusho group and 0.66 in the control group. These results show that PCB and PCQ accumulate in the subcutaneous fat tissue of patients with PCB poisoning (Yusho), as late as 17 years after diagnosis of the disease. The PCB and PCQ concentration levels in the subcutaneous fat tissue appear to be useful in diagnosis and evaluation of prognosis in this disease. Investigations of the elimination of PCB and PCQ in subcutaneous tissues should be done.