Tetsuzo Honda

ELECTRON MICROSCOPIC STUDY OF PORPHYRIAS

Electron microscopic examinations were performed on skin specimens obtained from six patients with erythropoietic protoporphyria and one patient with erythropoietic porphyria (Günther).

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.

A case of epithelioid sarcoma.

A case of a 58‐year‐old man with epithelioid sarcoma is reported.

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%.

SIX CASES OF ERYTHROPOIETIC PROTOPORPHYRIA

Six patients with erythropoietic protoporphyria, the most common of the porphyrias, were seen at Nagasaki University Hospital and studied clinically and histopathologically. Cutaneous changes were observed in all six patients and are considered to be the result of both protoporphyrin and sunlight. These changes were classified as either acute or chronic, and the chronic changes were examined histologically and revealed a perivascular accumulation of PAS positive material in the upper dermis.

Induction of Chronic Skin Changes in Intraperitoneally Hematoporphyrin‐Injected Mice with Metal Halide Lamp Irradiation

To induce chronic skin changes simulating human porphyria, mice which had been injected intraperitoneally with hematoporphyrin dihydrochloride were exposed to metal halide lamps. Clinical and histopathological findings in the mice were observed. Clinically, erythema, edema, erosion, necrosis and crust formation were initially seen in all of the mice treated. Hypertrophy of the skin, scarring, and deformities of the ear lobes followed gradually. Histopathological findings in these skin changes were mainly seen in the dermis and included infiltration of lymphocytes, proliferation of mast cells, dilatation and hyperemia of blood vessels in the upper dermis, and swelling and proliferation of connective tissues. PAS positive materials were deposited in the dermo‐epidermal junction and around the small blood vessels in the upper dermis. Using the direct immunofluorescent technique, the deposition of immunoglobulin G (IgG) was confirmed in the same areas, and some deposition of IgM, IgA and C3 was also observed. These findings are similar to those seen in patients with erythropoietic protoporphyria and porphyria cutanea tarda.