Shinkichi Taniguchi

Colchicine in the treatment of the cutaneous manifestations of Behçet's disease

Five patients with Behçets disease were satisfactorily treated with colchicine. Oral aphthosis, erythema nodosum‐like lesions and genital erosions improved greatly within a month as did laboratory findings. We believe colchicine to be the first choice in the management of the cutaneous and ocular lesions of Behçets disease.

Erythema multiforme: demonstration of immune complexes in the sera and skin lesions

In twenty patients with erythema multiforme we investigated circulating immune complexes and their deposition in the skin lesions. C1q‐binding activity was elevated in ten of twenty patients, and the platelet aggregation titre was high in three of twelve tested sera. Decreased levels of C3 were seen in two and of C4 in one out of eighteen patients. Direct immunofluorescence showed a deposition of C3, IgM or IgG in the blood vessel walls of the upper dermis in four of twelve patients. These findings may suggest that transient production of circulating immune complexes and their deposition play an important role in the pathogenesis of this disease.

Phospholipid base exchange in human leukocyte membranes: quantitation and correlation with other phospholipid biosynthetic pathways

The biosynthesis of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) by base-exchange reactions, and of PC and PE by the CDP pathways, was assessed in the membrane phospholipids of human leukocytes (neutrophils, lymphocytes, T lymphocytes, non-T lymphocytes, and monocytes). Of the three base-exchange activities, ethanolamine exchange was the highest and choline exchange the lowest in each leukocyte membrane. In the CDP pathways, ethanolaminephosphotransferase (EPT) and cholinephosphotransferase (CPT) had comparable activities. Among subpopulations of leukocytes, T lymphocytes showed the highest levels of each enzyme activity, and neutrophils showed the least. In contrast to the enzymes of the CDP pathways, each base-exchange activity was directly proportional to the Ca2+ concentration, but markedly inhibited by Mg2+. Despite this Ca2+ dependence, the base-exchange activities were increased in a dose-dependent manner by calmodulin antagonists and, except for ethanolamine exchange, inhibited by the addition of calmodulin; EPT and CPT activities were only slightly inhibited by calmodulin antagonists and were unaffected by calmodulin. PE formation in both neutrophil and lymphocyte base-exchange reactions was enhanced in a dose-dependent manner by the presence of low concentrations of bioactive stimulants (zymosan, 0.05-0.2 mg/ml; Con A, 0.5-2 micrograms/ml), while EPT and CPT activities were not increased by these cell stimulants. Taken together, our data suggest that base-exchange activity, the biological significance of which has been hitherto unclear, may be related to cell activation; in contrast, the CDP pathways appear primarily to involve the constitutive biosynthesis of phospholipids. Our data further suggest that ethanolamine required for base-exchange reactions is a precursor of PE, N-transmethylation of which can serve as a source of cell activation, leading to production of arachidonic through PC by mediation of phospholipase A2 activity.

Mycosis fungoides in the Tumor Stage Treated by PUVA: A Successful Trial in a 12-Year-Old Girl

Mycosis fungoides in the tumor stage was seen in a 12-year-old Japanese girl. Skin lesions were cleared after 1 month of PUVA treatment and have been in remission due to the effect of maintenance therapy.

Histamine metabolism in the arthus reaction

Histamine metabolism, i.e., concentration of histamine and activities of histamine-degrading enzymes, histamine-N-methyltransferase (HMT), and diamine oxidase (DAO), were examined in the Arthus reaction induced in guinea pig skin. The specific activity of HMT was 44.12 +/- 3.80 pmole/min/mg protein and was about 15 times greater than that of DAO in control specimens. However, HMT activity decreased time dependently to 35% of the control at 3 hr and to 10% 48 hr after the initiation of the reaction. DAO activity increased to 150% till 1 hr followed by a linear decrease to 35% at 6 hr and to 10% at 48 hr. Histamine concentration showed a prominent linear decrease to 15% of the control at 2 hr followed by an increase to about 85% at 6 hr. This biphasic change seemed to be well explained by the dynamic changes in the activities of histamine-degrading enzymes. Such decrease in enzyme activities were not observed in other experimentally induced inflammations including dinitrochlorobenzene allergic and croton oil dermatitis. The addition of tissue extract from the Arthus reaction sites resulted in about 30% inhibition in both of two enzyme activities, suggesting the presence of some inhibitory factor(s) in the reaction sites.

Effect of cyclosporin a on the membrane-associated events in human leukocytes with special reference to the similarity with dexamethasone

The effect of an immunosuppressive drug, cyclosporin A, and dexamethasone was assessed on the enzymatic reactions of membrane phospholipid in normal human lymphocytes and neutrophils. Incubation for 20 min with cyclosporin A markedly suppressed, in a dose dependent manner, phospholipase A2 activity and the release of prostaglandin E2 in lymphocytes, and slightly those in neutrophils, while no inhibition of phosphatidylethanolamine (PE)-N methyltransferase activity was observed. Choline phosphotransferase (CPT) activity was not inhibited by the drug, either. These inhibitory effects on enzyme activities of membrane phospholipid are similar to those of dexamethasone, although different incubation time of the drug was required to induce inhibitory effects. These findings suggest that cyclosporin A acts upon early membrane events in the activation of cells involved in inflammatory reactions; they further suggest that suppression of immune response by cyclosporin A is at least partly due to inhibition of phospholipase A2 in the plasma membrane of inflammatory cells. This inhibition reduces the production of cell membrane lyso-phosphatidylcholine (PC) and arachidonic acid from PC, which is produced by transmethylation of PE and cytidine diphosphate (CDP) choline pathway of which the last reaction to PC is mediated by CPT.

Regulation of the activity of histamine-N-methyltransferase from guinea pig skin by biogenic amines

Histamine-N-methyltransferase, a major histamine-degrading enzyme in the skin, was purified from guinea pig skin about 150-fold. The enzymological characteristics including pH optimum, Km values for substrates, and molecular weight were almost consistent with those reported in the brain. Regulatory mechanism of the enzyme activity by biogenic amines was investigated using the purified specimen. Serotonin, tryptamine, and 5-methoxytryptamine intensely inhibited the activity while tryptophan, melatonin, N-acetylserotonin, tryptophol, and 5-hydroxyindole acetic acid had no significant effects. Dopamine, tyramine, 3-methyltyramine, and phenylethylamine also inhibited the activity while no particular effects were obtained by adrenaline, noradrenaline, tyrosine, and DOPA. Spermidine and cadaverine caused significant but weaker inhibition. These amines acted competitively with respect to histamine, although varying manners were observed with respect to S-adenosyl-L-methionine. From these results, it was concluded that the enzyme activity was inhibited by such compounds in which a certain chemical structure, CH2-CH2-NH2 group neighboring the hydrophobic group, was contained. A possible mechanism of inhibition by the amines is postulated, and possible roles of such compounds in the inflammation by impairing the histamine metabolism is discussed.

Impaired histamine metabolism in the Arthus reaction induced in guinea-pig skin.

SummaryThe activities of two histamine-metabolizing enzymes, histamine-N-methyltransferase (HMT) and diamine oxidase (DAO), were examined in various types of experimentally induced cutaneous inflammations in guinea pigs. In intact guinea-pig skin, the specific activities of HMT and DAO were 24.8±1.7 pmol/min per milligram of protein or 0.930±0.097 pmol/min per milligram of the wet weight of skin specimen, and 6.0±0.7 pmol/min per milligram of protein or 0.189±0.011 pmol/min per milligram of the wet weight, respectively. Both enzyme activities were markedly reduced in skin lesions of the Arthus reaction (P<0.005), while those in dinitro-chlorobenzene allergic dermatitis, croton-oil dermatitis, and the intact areas in Arthus-reaction-induced aminals were almost within the normal limits. The activity of HMT decreased linearly with time from the onset of the Arthus reaction, reaching about 20% of the control activity at 48 h; the activity of DAO decreased even from the early stages of the reaction, and this decrease continued throughout first 48 h of the reaction. These results suggest that impaired histamine metabolism in the skin lesions of the reaction plays a distinct role in the formation and development of the Arthus reaction.

Impaired histamine metabolism in human erythematous dermatoses.

The specific activities of histamine‐N‐methyltransferase, the only enzyme to degrade histamine in human skin, were examined in 7 specimens from normal skin, 42 from erythema multiforme, erythema nodosum, erythema annulare or drug‐induced erythema and 12 from psoriasis or eczema. The enzyme activity was 3.45 ± 0.17 pmol/min/mg protein (mean ± S.E., n=7) in normal skin. The activities were significantly lower in 24 out of 30 freshly active lesional sites of erythematous dermatoses (lower than 2 S.D. from the mean in normal skin), while the activities in the central clearing areas were rather higher than those in the freshly active lesions. No significant changes were seen in the lesional skin of psoriasis or eczema. Decreased histamine‐degrading enzyme activity in the freshly active lesions of erythematous dermatoses may suggest the long lasting effect of the amine that was released in the lesions. In spite of the different clinical figures and multiplicity of etiologies, decreased histamine‐N‐methyltransferase activity was quite commonly observed, suggesting a similarity in the pathomechanisms of these dermatoses.

Methyltransferase and phospholipase A2 activity in the cell membrane of neutrophils and lymphocytes from patients with Behçet's disease, systemic lupus erythematosus, and rheumatoid arthritis

Phospholipid methylation and phospholipase A2 activation in the membrane of neutrophils and lymphocytes, which participate in the induction of cell activation, were assessed in patients with Behçets disease, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). [3H-methyl] incorporation and phospholipase A2 activity of neutrophils from active cases of Behçets disease and RA were significantly increased compared with normal controls. In lymphocytes from the patients with active Behçets disease and RA, a significant increase in methyltransferase activity and a marked enhancement of phospholipase activity were found. A modest increase in these two membrane phospholipid enzyme activities was observed in lymphocytes of patients with active SLE. In addition, these enzyme activities were significantly enhanced in normal leukocytes preincubated with serum from patients with active SLE and malignant RA. The potentiated functions of neutrophils and lymphocyte abnormalities in the patients tested thus seem to be at least partly due to an increase in these enzymatic activities in the cell membrane.