Hisayo Kachi

The effect of electrical acupuncture-stimulation therapy using thermography and plasma endothelin (ET-1) levels in patients with progressive systemic sclerosis (PSS).

In all 11 patients with progressive systemic sclerosis (PSS; Barnett type I, 2; type II, 5; type III, 4 cases; male 1; female 10 cases; 45.2 +/- 10.2 years-old), 6 cases of scleroderma spectrum disorders (SSD, male 1; female 5 cases; 51.2 +/- 13.2 years-old) and 7 healthy controls (HC, male 1; female 6 cases; 43.1 +/- 8.4 years-old) were entered to be examined. The plasma endothelin-1 (ET-1) levels of PSS, SSD and HC were 1.98 +/- 0.69, 1.76 +/- 0.39 and 1.15 +/- 0.38 pg/ml, respectively. After the stimulation with the low frequency electrical current, electrical acupuncture, for unilateral side of hand/arm (30 min), the plasma ET-1 levels decreased in 10 cases of PSS treated (1.61 +/- 0.45 pg/ml), but no change of plasma serotonin levels. In 4 of 6 cases of SSD, plasma ET-1 levels increased (2.06 +/- 0.39 pg/ml), however, nitrate levels increased and serotonin decreased in 3 of 5 cases of SSD. In 6 cases of HC treated with the electrical acupuncture, the plasma ET-1 levels increased (1.72 +/- 0.58 pg/ml). Thermographically, 9 of 11 cases of PSS and 5 of 6 cases of SSD showed temporally temperature-elevation of hand/fingers not only in treated sides, but also in non treated sides, although none of 7 HC showed temperature-elevation of hands/fingers. The decrease in plasma ET-1 levels due to the electrical acupuncture was thought to induce the vasodilatation and elevate the surface temperature in patients with PSS. These results will provide an excellent basis to study the efficacy of electrical acupunctural stimulation.

Plasma levels of molecular markers of blood coagulation and fibrinolysis in progressive systemic sclerosis (PSS)

Seventy-four patients with PSS were evaluated with regard to plasma concentration of blood coagulation and fibrinolysis factors: fibrinogen (Fbg), prothrombin time (PT), active partial thromboplastin time (APTT), protein C, thrombin-antithrombin III complex (TAT), antithrombin-III (AT-III), factor XIII (XIII) fibrinopeptide A (FPA), alpha 1-antitrypsin (alpha 1-AT), plasminogen (Pmg), alpha 2-plasmin inhibitor plasmin complex (PIC), alpha 2-plasmin inhibitor (alpha 2-PI), alpha 2-macroglobulin (alpha 2-MG), fibrinopeptide B beta 15-42 (FPB beta-15-42) and soluble fibrin monomer complex (SFMC), FDP (fibrin degradation product) and D-dimer. They were also evaluated with regard to platelet-derived proteins: beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), thromboxane B2 and 6-keto-prostaglandin F1 alpha (6KF). In the coagulation/fibrinolysis systems high plasma levels of TAT, AT-III, FPA, alpha 2-MG and FPB beta 15-42 could be demonstrated in more than 50% of total PSS patients. There was no statistical correlation between those of TAT and AT-III. Plasma levels of PIC, D-dimer, FDP and SFMC were not always high. There was no statistical correlation between those of TAT and PIC. These data lead us to consider that alpha 2-MG may play an important role for inhibiting PIC, which accelerates the conversion from fibrin into FDP. Subsequently, there were high plasma levels of FPB beta 15-42 converted from fibrin monomer. These data seem to be indicative of an involvement of coagulation and platelet disorder in PSS. These platelet-vessel system disorders might be closely related to the pathophysiology of PSS.

Is there circadian variation of plasma endothelin (ET-1) in patients with systemic scleroderma (SSc)?

Forty-three patients with systemic scleroderma (SSc), 10 with non-SSc (6 cases of systemic lupus erythematosus and 4 cases of dermatomyositis), 14 cases of mild- or non-sclerotic type of scleroderma with capillaroscopic abnormalities of nailfolds (SSD; scleroderma spectrum disorders) and 10 healthy volunteers (HC) were subjected to examination of plasma levels of endothelin-1 (ET-1). The sex ratios (male/female) in the patients with SSc, non-SSc and HC were 7:36, 4:6 and 0:10, and the ranges of their ages were 22-74, 19-78 and 33-62 years old, respectively. The plasma levels of ET-1 in SSD, SSc (Barnett I;15), SSc (Barnett II;16), SSc (Barnett III;12 cases), non-SSc and HC were 1.67 +/- 0.37 2.04 +/- 0.58 2.04 +/- 0.68 1.85 +/- 041 191 +/- 0.7 and 1.31 +/- 0.34 pg/ml, respectively, confirming previous results from other laboratories. The plasma levels of ET-1 statistically differ between each collagen disease (SSD, SSc and non-SSc) and HC using Students t-test (P < 0.05). Although a statistically significant difference was obtained in the plasma levels of ET-1 between the SSc group (6 cases) and HC (6 cases) measured at 06:00, 12:00, 18:00 and 24:00 h, there was no significant circadian variation of plasma levels of ET-1 at these times in both the SSc group and HC. The present study revealed that (1) the ET-1 level in HC showed no circadian fluctuation, and remained at a low level (0.8-1.6 pg/ml). (2) When compared to HC, ET-1 in blood plasma of patients with SSc was elevated (0.3-3 pg/ml) throughout the day and night (P < 0.05). (3) ET-1 tended to increase more at midnight (24:00 h) in the SSc group without PSL treatment, though no statistical significance was obtained. (4) TAT showed a significant increase at noon (12:00 h) suggesting coagulation activity in patients with SSc, but PlC did not show a significant increase compared to HC. In conclusion, the observed increase of vasoconstrictive ET-1 in the patients with SSc throughout the day and night may make maintenance of peripheral blood flow more difficult, may have some biological origin and should be further investigated.

Circadian variations of plasma levels of blood coagulation/fibrinolysis molecular markers in progressive systemic sclerosis (PSS)

We measured plasma levels of the blood coagulation/fibrinolysis molecular markers, thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA), alpha 2-plasmin inhibitor plasmin complex (PIC), beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), at 6:00, 12:00, 18:00 and 24:00 in 10 female patients with progressive systemic sclerosis (PSS) (severe and mild sclerosis groups, each n = 5), 3 cases of dermatomyositis (DM) (M:F = 2:1) and 5 female healthy controls (HC). Corticosteroid (predonisolon; 20-25 mg/day) was administered orally in six patients with PSS and dermatomyositis longer than one month. Plasma levels of TAT increased more than 3 ng/ml in 8 out of 10 cases (80%) of PSS, while the levels increased in only 2 of 8 cases (25%) of the non-PSS groups (DM and HC). The severe sclerosis group of PSS showed a peak at 6:00 in the circadian variations of plasma levels of TAT and FPA, while the mild sclerosis group of PSS showed a peak at 12:00 or 24:00, and both DM and HC at 24:00. However, there was no significant peak in circadian variations of the plasma levels of PIC in the severe sclerosis group of PSS, although there was a peak at 24:00 in other diseases. The synchronized peaks of TAT and PIC were seen in 4 of 8 cases (50%) of the non-PSS group. On the other hand, this synchronization was only detected in 1 of 10 cases (10%) of PSS. The plasma levels of beta-TG and PF4 increased in 8 of 10 cases (80%) of PSS, but these levels did not increase in 8 non-PSS cases. Circadian variation of plasma levels of beta-TG showed a peak at 6:00 in the severe sclerosis group of PSS, while the mild sclerosis group of PSS, DM and HC revealed peaks at different times of 18:00, 24:00 and 12:00, respectively. Additionally, the plasma levels of beta-TG increased more than those of PF4 in the treated group with corticosteroid, although both beta-TG and PF4 revealed a statistically significant correlation in the non-treated group. These results may suggest abnormalities of not only platelet activity, but also of blood coagulation/fibrinolysis system in both severe and mild sclerosis groups of PSS.

Pigmentation abnormalities in systemic scleroderma examined by using a colorimeter (Choromo Meter CR-200)

Cutaneous colors of the dorsum of the hands (A), the distal forearms (B; 5 cm from the wrists), the proximal forearm (C; proximal 1/3 from the elbow) and sternal skin region (D) in patients with systemic scleroderma (73 cases; M:F = 16:57) systemic lupus erythematosus (SLE) or dermatomyositis (27 cases; M:F = 7:20) and healthy controls (HC) (36 cases; M:F = 8:28) was characterized by a XYZ colorimetric system (CIE, 1931) using a colorimeter (Choromo Meter CR-200, Minolta Camera Co. Ltd., Osaka). The index Y, which means color value shows a lower value in male HC and in patients with systemic scleroderma, especially in the more severe type with hyperpigmentation (score 5-6; the system proposed by Ishikawa) than that of female HC. The values of indices x and y, which relate to reddish (erythema with hyperpigmentation) and greenish color (pale), respectively, were higher in the exposed portion of the severe type of systemic scleroderma with hyperpigmentation, especially male and older patients, and in unexposed portions of the female group without hyperpigmentation. Histopathologically, there was prominent pigmentation in the upper dermis of the forearm in the severe type of systemic scleroderma, so that melanin quantity may be closely related to the decrease in index Y. There was no statistical significance in the value of indices Y, x and y between HC, SLE and dermatomyositis. This method may contribute not only to diagnosis of systemic scleroderma and differentiation from other collagen diseases, but also studies of clinical follow-up and effects of medication.

Ultrastructural Observation of Platelets from Patients with Progressive Systemic Sclerosis (PSS)

We observed the ultrastructure of platelets from patients with PSS (7 cases; 48.2 ± 12.3 y‐old; M:F= 1:6) and healthy controls (HC) (5 cases; 44.8 ± 8.0 y‐old; M:F=1:4) by using transmission (TEM) and freeze‐fracture electron microscopy (FEM). The open canalicular system (OCS) connected with the plasma membrane (PM) formed pinhole‐like invaginations (50 nm in diameter) in the cleaved face (P‐face) of the plasma membrane seen from the outside of the platelets and sharply elevated structures in the cleaved face (E‐face) of PM seen from the inside of the platelts by FEM. The density of OCS on the surface of the platelets from PSS patients was 3 ± 1/μm2, which was higher than that from HC (1 ± 0.5/μm2) (p<0.02). Dome‐shaped structures, which clearly differ from OCS and were 80–150 nm in diameter without intramembranous particles, were seen in the P‐face, and the complementary depressed structures were seen in the E‐face. These structures were thought to be vesicles fused onto the PM of the platelets. The total volume of platelets (7.62 ± 0.11 μm3), total volume of granules (0.79 ± 0.01 μm3) and vacuoles including OCS (0.78 ± 0.05 μm3), and the total surface area of platelets (17.25 ± 1.30 μm2) from four PSS patients calculated by the morphometrical method were similar to those from four HC (7.32 ± 0.25 μm3, 0.76 ± 0.03 μm3, 0.80 ± 0.05 μm3, 18.75 ± 0.35 μm2, respectively); there were no statistical significances between the data from PSS patients and HC. The total volumes of vacuoles in platelets from both PSS patients and HC significantly decreased after a 2 min‐vibration stress of the hands (p<0.02) and the total volume of granules in platelets from PSS patients decreased significantly after the same stress (p<0.002), although that from HC showed no similar significant change. However, there were no statistically significant differences in total volume or total surface of platelets from PSS patients and HC after the stress. These data may suggest that depletion of granules occurred due to activation of platelets from PSS patients following a secretion of their proteins, because their plasma protein levels were elevated after the stress (Jpn J Dermatol, 98; 1205, 1988). Higher density of OCS on the surface of the platelets from PSS patients may play an important role in secretion of their proteins, although the detailed mechanism of secretion of specific proteins derived from platelet granules is still unknown. These ultrastructural abnormalities of platelets may correlate with some involvement of a platelet disorder and with a possible role for the activation of platelets from PSS patients.

Histopathological and capillaroscopical features of the cuticles and bleeding clots in ring or middle fingers of systemic scleroderma patients.

Sixty-three patients with systemic scleroderma (SSc) (Barnett I, 41; Barnett II, 17; Barnett III, 5), 14 with systemic lupus erythematosus (SLE), 9 with dermatomyositis (DM) and 10 healthy controls (HC) were subjected to histopathological examinations of the cuticles of ring or middle fingers. The sex ratios (male/female) in the patients with SSc, SLE, DM and HC were 7:56, 5:9, 5:4 and 5:5, and the ages were 22-74, 19-78, 45-70 and 13-78 years old, respectively. Biopsy samples were taken from the central portion of the cuticles, which showed the most severe change of elongation with or without bleeding clots of cuticle-proximal nailfolds (BC). Histopathologically, 61 (96.8%) cuticles of SSc patients consisted of the upper (U), middle (M) and lower (L) layers, which represent obliquely stacked, parabolic, and parallel stacked layers, respectively. The middle parabolic layer appeared to discharge homogenous eosinophilic globular deposits (ED). On the other hand, this typical three-layer-nail pattern was seen only in 9 (64.3%) of SLE, 3 (33.3%) of DM and none of HC, in total 12 (36.4%) of the non-SSc group, which included SLE, DM and HC. In SSc, there were statistical correlations (R2) between ED and BC, ED and cuticle-elongation, cuticle-layer and cuticle-elongation, ED and cuticle-layer, BC and cuticle-elongation. Capillaroscopically, bleeding clots located in the middle layer with ED of the cuticles in eight patients with SSc were transported rapidly within 1-2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Parent and child cases of malignant melanoma.

悪性黒色腫の親子発症症を経験し, 稀な症例と考え, 若干の比較, 検討を行った。症例1, 80歳男。左足縁部腫瘤に気付き生検後, 悪性黒色腫の診断のもと当科入院。手術時診断; nodular type, stage 3, level 5。症例2, 48歳男 (症例1の長男)。左膝窩の黒色斑に気付き, 悪性黒色腫の臨床的診断のもと当科入院。手術時診断; nodular type, stage 3, level 4。報告2症例の比較, 家族的素因などを検討した。