Immunity to infectious organisms is constructed of both innate immunity and acquired immunity. Dendritic cells (DC) including Langerhans cells (LC) as a member and belonging to innate immune system play a crucial role in regulating the acquired the immune response, via their expression of several co-stimulatory molecules and production of cytokines. It is clear that the immune system responds not only to infectious organisms but also to simple chemicals. The allergic contact hypersensitivity reaction is a good example of the immune response to simple chemicals. In contrast to the immunity to microorganisms, however, the role of the innate immune system to simple chemicals still remains unclear. This paper summarizes the response of DC to simple chemicals and demonstrates the mechanism by which they respond to chemicals such as haptens by augmenting their expression of costimulatory molecule and increasing cytokine production. Finally, the biological significance of allergic contact sensitization is also discussed.
Pyodermia chronica glutealis (PCG) is characterized by recurrent infections, and its pathogenesis has not been clarified. In this study, to evaluate the functions of neutophils in PCG, we examined superoxide (O2–) generating activity, phagocytosis and chemotaxis of neutrophils in an individual with PCG during exacerbation and remission periods. The results revealed that O2– generation by fMLP, PMA and opsonized zymosan (OZ) was enhanced during exacerbation period. During the remission period, O2– generation by PMA and OZ was returned to normal control levels ; however, O2– generation by fMLP was markedly reduced compared with that of normal controls. In addition, phagocytosis of OZ was increased during exacerbation period and returned to control levels during the remission period. In contrast, chemotactic activity for C5a did not change during the exacerbation and remission periods, and remained the same as that of normal controls. Together, these observations indicate that, in PCG, neutrophil functions are enhanced during the exacerbation period and return to the control levels during remission periods.
Background: The sentinel lymph node (SN) is the first node or nodes to drain a cutaneous melanoma. Sentinel lymph node biopsy (SNB) is performed to determine whether regional metastases are present. The authors report our experience with the techniques of blue dye, lymphoscintigraphy, and a gamma probe of sentinel lymph node biopsy for malignant melanoma. SNB was attempted in 61 patients with clinical node metastasis negative cutaneous melanoma from October 1997 to September 2002 in the Dermatology Division, of National Cancer Center Hospital. Fifty-one patients were injected with blue dye alone. SNs were identified in 42 patients (82.3%). Ten patients underwent lymphoscintigraphy preoperatively. A gamma probe and blue dye helped in localizing the SN. The SNs were identified in 10 patients (100%) by the triple techniques. Collectively, we could identify the SNs in 52 patients (85%). SN metastasis was found to be negative in 39 (75%) of the 52 patients ; the other 13 patients (25%) had one or more positive SNs. Four (10.3%) of the 39 patients developed a recurrence despite having no evidence of metastatic SN. Continuously, we reexamined 57 SNs from the 39 patients reported as negative for malignant melanoma metastasis following routine HE (hematoxylin and eosin) stain. Metastases were apparent in 13 of these 52 patients, and 16 of the 73 SNs. Using the remaining 57 SNs from the 39 patients, we examined immunohistochemically stained deeper sections SNs with antibodies to Mitf (microphthalmia transcription factor), S-100, HMB-45, and Melan-A. These deeper serial sections and immunohistochemical stains detected microscopic metastases in 4 (10.3%) cases and 5 (8.7%) SNs that had been reported as negative for metastasis by routine pathological analysis.
In order to elucidate the pathogenesis and determine the adequate treatment for the so-called “dirty neck” that is seen in the patients with adult-type atopic dermatitis (AAD), we performed morphological and physiological studies of hyperpigmented lesions of the neck in 27 patients with AAD. Three patterns of hyperpigmentation were noted clinically: a) zebra-like b) diffuse, and c) intermediate. Of these three, zebra-like pigmentation was most peculiar and problematic for patients with AAD. Analyses of spectral reflectance and magnified images recorded with a digital camera and a videomicroscope revealed that the zebra-like hyperpigmentation consisted of less pigmented skin around hair follicles grouped in a necklace-like arrangement and dusky hyperpigmented belts with melanophage deposition between the hair follicles. A significant decrease in the conductance of the stratum corneum was found in patients with AAD when compared to that measured at the neck of normal subjects. Although one-year treatment with topical tacrolimus improved this damaged hydration capacity of the stratum corneum, no improvement in skin color (L* and a*) was achieved. However, we found a mildly positive correlation between duration of the disease and skin brightness (L*), indicating that this cosmetically troublesome hyperpigmentation will gradually improve if adequately treated.
In order to observe skin responses to neurotransmitters, we used low level reactive laser irradiation directed at the periphery of the stellate ganglion of atopic dermatitis patients and measured changes in the target area after injecting acetylcholine (Ach), methacholine chloride (MCH), and vasoactive intestinal polypeptide (VIP). The Ga-Al-As laser (MEDILASER SOFT 1000, Mochida JAPAN) was directed continuously for 20 minutes at a wavelength of 830 nm and a light output of 1,000 mW at the right side of the stellate ganglion. Following irradiation, Ach (1.0 mM, 0.05 ml）, MCH (0.2 mM, 0.05 ml）and VIP (3.0 uM, 0.05 ml) were injected into the skin of the right forearm and back, and the resulting flare and the delayed branch were measured. The Ach skin test indicated that the target area decreased in six out of eight in-patients who were treated five times a week (a total of 10 times). Furthermore, the MCH skin test indicated that the target area size decreased in three subjects, while the VIP skin test indicated an increase in five subjects after ten treatments. However, the Ach, MCH, and VIP skin tests performed on the out-patient group (10 individuals, once or twice per week) failed to yield the same results. This experiment suggests that low reactive level laser therapy directed at the region surrounding the stellate ganglion can be effective in reducing the delayed branch phenomenon induced by the injection of Ach.
Because patients with polymyositis or dermatomyositis associated with serum anti-aminoacyl-tRNA synthetase antibody, in which anti-Jo-1 antibody forms a vast majority, frequently have interstitial pneumonia, arthralgia, and Raynaud’s phenomenon as well as myositis, they are recognized as a clinical subset under the name of antisynthetase syndrome. A 64-year-old man presented with muscle weakness, arthralgia, general fatigue and skin changes including hyperkeratosis, scaling and fissuring, which were located on the ventral and lateral aspects of his fingers and the dorsal aspect of the finger joints of his bilateral hands. Nailfold bleeding was observed on his fingers, but no other cutaneous signs indicative of dermatomyositis were noted. A skin biopsy from the cutaneous lesion revealed chronic dermatitis-like pathological changes with scattered images of satellite cell necrosis. Serum CPK was 6,687 IU/l. The electromyography showed a myogenic pattern, and a muscle biopsy showed degeneration and atrophy of the muscle fibers. He also had interstitial pneumonia, and his serum contained anti-Jo-1 antibody. He was given a diagnosis of antisynthetase syndrome, and his skin changes were considered to be “mechanic’s hand”. We reviewed the reported cases of mechanic’s hand and discussed the relationship between mechanic’s hand and antisynthetase syndrome.
Systemic sclerosis (SSc) is an autoimmune disease characterized by a high frequency of circulating autoantibodies to a variety of cellular components. Anti-RNA polymerases I and III antibodies are specific for SSc, and it is known that clinical features associated with this antibody include a high frequency of heart and kidney involvement and a poor survival rate. We describe a 68-year-old man with diffuse cutaneous SSc who presented with this antibody. Renal vascular resistance evaluated by color-flow Doppler ultrasonography revealed high pulsatility index (PI) in the renal interlobar arteries. However, he did not show any clinical evidence of renal insufficiency. This suggests that Doppler ultrasonography can detect latent and subclinical renal vascular damage. Trandolapril (angiotensin converting enzyme) was given orally, and the PI was decreased. Color-flow Doppler ultrasonography is a useful and non-invasive technique for evaluating subclinical renal vascular damage of the kidneys in SSc patients without scleroderma renal crisis. Renal vascular resistance in patients with anti-RNA polymerase antibody need to be checked periodically to detect any increase in renal vascular resistance at an early stage.
Objective: To compare the international standard regimen of itraconazole pulse therapy with low daily-dose pulse therapies, which are widely conducted in Japan. Design: Randomized, double-blind, parallel-group comparative study. Patients: 186 patients with a big toenail showing onychomycosis symptoms such as opacity. Intervention: Patients were assigned to Group I (200 mg/d, 3 cycles), Group II (200 mg/d, 6 cycles) or Group III (400 mg/d, 3 cycles). All received itraconazole orally. Main Outcome Measure: Cure or complete response―assessment based on improvement in the opacity ratio and microscopic examination. Results: The clinical response rates (cure plus complete response) at week 24 were Group I: 14.9%; Group II: 25.5%; Group III: 32.7%. At week 48, 17 patients were cured in Group III-up from 3 at week 24. At week 48, the areas under the nail plate concentration-time curves (AUC) was Group I: 2,547±1,624 ng·h/g; Group II: 4,155±2,915 ng·h/g; Group III: 10,104±7,161 ng·h/g. There were no differences between the three groups with regard to the incidence of adverse drug reactions. Conclusions: The clinical response rates demonstrated that the pulse therapy of 400 mg/d itraconazole for 3 cycles was most effective. The significantly higher Group III AUC (week 48) (p<0.01) suggests that, when the same total amount of itraconazole is administered, itraconazole remains in nail plates longer following pulse therapy with a higher daily dose. It was also suggested that clinical efficacy correlated with the duration of the presence of itraconazole.