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Biomedical subjects

Seiji Kawana

Publications and source records attributed to Seiji Kawana.

At least 19 recordsLinked to original sources

Increased expression of RANTES, CCR3 and CCR5 in the lesional skin of patients with atopic eczema.

BACKGROUND: Atopic eczema (AE) is a relapsing inflammatory disease based on IgE sensitization and characterized by peripheral blood eosinophilia and eosinophil infiltration into the lesional skin. In the patch test reaction of AE by allergens, an increased infiltration of activated eosinophils has been demonstrated peaking at 24-48 h. Regulated on activation normal T cell expressed and secreted (RANTES/CCL5) is a chemokine that induces eosinophil migration, and CCR3 and CCR5 are the receptors of RANTES. OBJECTIVE: In order to further clarify the pathomechanisms of eosinophil infiltration in ongoing chronic inflammation in the skin of patients with AE and its relation to disease severity, we examined the expression of RANTES and its receptors CCR3 and CCR5 in challenged and unchallenged lesional skin of AE. METHODS: We examined the number of RANTES+ cells, CCR3+ cells, CCR5+cells, activated (EG2+) eosinophils and CD3+ T cells in normal skin of healthy volunteers, and in challenged lesional skin (24 h after mite patch test) as well as unchallenged lesional skin of AE patients by immunohistochemistry. The cellular source of RANTES, CCR3 and CCR5 was analyzed by double immunohistochemistry using specific antibodies to RANTES, CCR3 or CCR5, and antibodies to ECP (EG2) or CD3. RESULTS: The numbers of RANTES+ cells, CCR3+ cells, CCR5+ cells, EG2+ cells and CD3+ cells were all significantly increased in challenged (mite patch-tested) lesional skin of AE patients as compared to those in unchallenged lesional skin and normal skin. The numbers of these cells in unchallenged lesional skin were greater than those in normal skin. The number of EG2+ cells in the unchallenged lesional skin correlated with both the peripheral blood eosinophil count and the SCORAD index. The number of EG2+ cells in challenged lesional skin correlated with the number of CCR5+ cells. Activated eosinophils and T cells expressed RANTES and various proportions of these cells were CCR3+ and CCR5+ in both challenged and unchallenged lesional skin. CONCLUSION: Taken together, these results suggest that RANTES as well as its receptors CCR3 and CCR5 may play important roles in the orchestration of eosinophil infiltration in ongoing chronic inflammation in AE, and also reflect the severity of disease.

Adult↗

Role of substance P in stress-derived degranulation of dermal mast cells in mice.

BACKGROUND: The interaction between nerves and mast cells can effect regulation of the immune system and inflammatory responses. Recent studies have shown that various stressors can induce degranulation of dermal mast cells in animals. OBJECTIVES: This study was conducted to confirm that substance P (SP) was involved in the degranulation of dermal mast cells in stress conditions. METHODS: Using a communication box system, foot shock stress (FS) and psychological stress (PS) were administered to mice and the degranulation rate of dermal mast cells, the number of SP-positive nerve fibers and changes in SP content were determined. The inhibitory effect of a non-peptide NK1-receptor antagonist on these changes was investigated. RESULTS: Both FS and PS significantly enhanced the degranulation of dermal mast cells and increased the number of SP-positive nerve fibers. FS significantly decreased dermal SP content whereas SP was increased by PS. These changes were inhibited by intraperitoneal injection of NK(1) receptor antagonist. CONCLUSIONS: It was considered that SP released from the nerve ending, had an important role in the degranulation of dermal mast cells. Results of this study suggest that the tachykinin receptor antagonist exhibited an inhibitory effect on aggravated stress-induced dermatitis.

Androstanes↗

Papulonecrotic tuberculid with spontaneous remission.

We describe a 62-year-old Japanese woman who had skin lesions involving her extremities, chest and back that showed spontaneous remission. The skin lesions consisted of slightly atrophic scars and crusted, reddish or necrotic papules. A tuberculin test showed induration and bulla, which was regarded as strongly positivity. Histopathologically, a tuberculoid granuloma with necrosis was present in the upper dermis and the deep dermis, including the adipose tissues. Bacterial cultures were not positive from sputum, urine or stool, and the chest X-P was also normal. After skin biopsy, all the lesions disappeared within 1 month. No relapse was noted in the entire body.

Biopsy, Needle↗

Urticarial vasculitis appearing in the progression of systemic sclerosis.

We report a case of urticarial vasculitis that appeared during the course of limited cutaneous systemic sclerosis. The urticarial lesions responded to systemic administration of prednisolone. After the appearance of urticarial vasculitis, the progression of scleroderma in distal sites of her elbow and knee joint became apparent. We consider this case to be consistent with limited cutaneous systemic sclerosis. The patient started treatment with prednisolone and her edema as well as scleroderma softened gradually. We analyzed, by immunohistochemistry, the number of tryptase-positive mast cells of this case in the lesions of urticarial vasculitis as well as systemic sclerosis. The number of tryptase-positive mast cells in the lesions of urticarial vasculitis as well as systemic sclerosis was significantly increased compared to normal skin (P < 0.05 and P < 0.005, respectively). We demonstrate that, in the present case, mast cells might be involved in both courses of urticarial vasculitis and systemic sclerosis as a common factor.

Diagnosis, Differential↗

Dynamic changes in nerve growth factor and substance P in the murine hair cycle induced by depilation.

Increasing evidence suggests that various neurotrophins and neuropeptides play an important role in the progression of hair follicle cycling. Among them, nerve growth factor (NGF) and substance P (SP) have attracted special interest recently. However, the interaction between these factors during hair cycling has not yet been systematically studied. We therefore investigated the mutual relationships between NGF and SP and the mechanism by which the anagen stage of the hair cycle is initiated. Fluctuations in numbers of SP-positive nerve fibers and variations in amounts of SP, NGF, and another neurotrophic factor, glial cell-derived neurotrophic factor, in skin in the C57BL/6 mouse depilation-induced hair cycle model, together with the spatiotemporal expression patterns of each of these factors, were followed simultaneously by enzyme-linked immunosorbent assay and immunohistochemistry. The main finding was that a surge in NGF expression and a rapid increase in NGF content in skin is an initial event within 1 day after depilation, followed by elevation of SP content and numbers of SP-containing fibers 2 days after the increase in NGF. Our findings suggest that a rapid and abundant increase in NGF plays a key role in the induction and progression of anagen hair cycling through keratinocyte growth promotion. NGF may also induce plastic changes such as sprouting and hyperplasia in dermal nerve fibers and enhance their SP production. Elevated levels of SP in skin may additionally contribute to the progression of consecutive anagen hair cycles.

Adipose Tissue↗

Light-emitting diode phototherapy at 630 +/- 3 nm increases local levels of skin-homing T-cells in human subjects.

BACKGROUND AND AIMS: Red light phototherapy with laser sources has been used successfully for a number of indications. A new generation of quasimonochromatic 630 +/- 3 nm light-emitting diode (LED) systems has recently been yielding good results for the same indications, but no study has examined changes in visible red light irradiated skin at an immunological level. This study was thus designed to examine changes in skin-homing T-cell levels induced in normal human skin by visible red LED energy. SUBJECTS AND METHODS: Six adult male volunteers (35 approximately 48 years old) who satisfied all study criteria had the skin over the lateral aspect of the leg irradiated once per week for 8 weeks with a visible red (630 +/- 3 nm) LED-based system, with irradiance of 105 m/cm2, 15 minutes/session, and a radiant flux of 94 J/cm2. Skin biopsies were performed after the eighth treatment session, and cultures were prepared to assay the type and quantity of skin-homing T-cells using qualitative and quantitative polymerase chain reaction (PCR) techniques. Ultrastructural changes were also assessed with transmission electron microscopy. RESULTS: Transmission electron microscopy revealed mild fibroplastic changes in fibroblasts, with no acute inflammatory changes throughout the treatment session. Qualitative PCR showed the presence of both Th-1 and Th-2 T-cells, and quantitative PCR showed an increase in the numbers of both types of skin-homing T-cells, much more so for Th-2 than for Th-1. CONCLUSIONS: Visible red LED irradiation appears to activate the skin-homing immune system.

Adult↗

Superior vena cava syndrome: a case report.

We report a case of superior vena cava syndrome (SVCS) caused by squamous cell lung carcinoma in a 49-year-old man. He presented with severe edema of the face and upper half of the body with numerous dilated and tortuous cutaneous veins. Although we initially considered this case to be a drug eruption because the patient had repeated episodes of worsening clinical presentation whenever he took nonsteroidal anti-inflammatory drugs (NSAIDs), persistent and characteristic dermatologic findings led us to the diagnosis of SVCS. After balloon angioplasty of the left subclavian vein to the SVC, dermatologic findings markedly disappeared. Bronchoscopy and biopsy results revealed underlying squamous cell lung carcinoma.

Carcinoma, Squamous Cell↗

Increased expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and matrix metalloproteinase-13 in lesional skin of bullous pemphigoid.

BACKGROUND: Matrix metalloproteinase (MMP)-2, MMP-9 and MMP-13 can degrade type IV collagen which is the major component of the basement membrane zone (BMZ). In bullous pemphigoid (BP), the separation occurs within the BMZ. OBJECTIVE: To evaluate the involvement of MMPs in the pathogenesis of BP, we examined the expression of MMP-2, MMP-9 and MMP-13 in the lesional skin of BP patients. METHODS: The expression of MMP-2, MMP-9, MMP-13, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 was analyzed by immunohistochemistry in the lesional skin of BP patients in comparison with that in normal human skin. Next, the cellular sources of MMP-2, MMP-9 and MMP-13 were analyzed by double immunohistochemistry. Finally, the levels of these MMPs in the serum and blister fluid of BP patients were measured by ELISA. RESULTS: The number of cells expressing MMP-2, MMP-9 and MMP-13 were significantly increased in the lesional skin of BP patients as compared to that in normal skin. Although the number of cells expressing TIMP-1 and TIMP-2 were also increased in the lesional skin of BP patients as compared to that in normal skin, the ratio of MMPs to TIMPs in the lesional skin of BP patients was high (2.4:1). T cells comprised the major source of MMP-2, MMP-9 and MMP-13, while a proportion of mast cells and eosinophils also expressed these MMPs. Furthermore, marked expression of MMP-2 was detected in the epidermal keratinocytes. The levels of these MMPs in the blister fluid were significantly greater than those in the serum. CONCLUSION: These results suggest that MMP-2, MMP-9 and MMP-13 may be involved in the mechanism of blister formation in BP and that besides infiltrating inflammatory cells, structural cells like epidermal keratinocytes may also participate in the induction of blister formation in BP.

Aged↗

Prevalence of human papillomavirus DNA sequences in verrucous carcinoma of the lip: genomic and therapeutic approaches.

We examined the presence of human papillomavirus (HPV) DNA sequences in tissues of verrucous carcinoma (VC) of the lip. Detection and typing of HPV DNA was performed using polymerase chain reaction with sequence analysis and restriction fragment length polymorphism analysis. All tissues of VC contained HPV DNA and one of recurrent case was infected with four different HPV DNAs including high risk types. Seven different HPV types were detected in VC, of which (accession no. in EMBL/GeneBank/DDBJ databases) has been described as a partial sequences from an unknown HPV type. Sequence analysis showed that HPVX is related to HPV-20 (74.8% sequence homology). These results indicate that various mucosal and cutaneous HPVs of high risk types are associated with the one of pathogenesis of VC of the lip. In addition, the relationship between VC of the lip and HPV infection is discussed, as is therapy against VC.

Adult↗

A case of peripheral T-cell lymphoma unspecified involving subcutaneous tissue.

A 36-year-old man presented with a 3-year-old red-brown plaque with subcutaneous nodules on his left thigh. Although a similar lesion was observed on his right thigh 3 years earlier, it spontaneously disappeared 1 year later. However, the lesion on the left thigh was growing larger. Histologically, the lesion showed a diffuse and dense infiltration of atypical lymphocytes extending from the superficial dermis to the subcutaneous tissue. Severe lobular panniculitis, composed of small- and medium-sized atypical lymphocytes and large normal histiocytes, was observed in the subcutaneous adipose tissue. Immunohistochemical studies revealed a post-thymic T-cell phenotype. A genetic analysis demonstrated a rearrangement of the T-cell receptor chain gene. The left skin lesion also gradually disappeared after skin biopsy without therapy, and he continues to be in remission.

Adult↗

A case of hypereosinophilic syndrome.

A 22-year-old man developed papules on his legs in November of 2001, which then spread to cover almost his entire body. He was treated with a topical steroid and PUVA therapy at another hospital. The symptoms showed no improvement, and, in February of 2002, he came to our hospital. Examination revealed hypereosinophilia, and, because he had symptoms of organ involvement by the heart, lung, and inguinal lymph nodes as well as the skin, we diagnosed him with idiopathic hypereosinophilic syndrome (HES). The patient was treated with oral prednisolone at a dose of 60 mg/day, and his cutaneous lesions and other organ symptoms improved.

Administration, Oral↗

Pemphigoid nodularis: two case studies and analysis of autoantibodies before and after the development of generalized blistering.

We report 45- and 61-year-old women with generalized prurigo nodularis-like eruption whose clinical, histologic and immunopathologic features were consistent with the diagnosis of pemphigoid nodularis. In one case, nodular lesions preceded the onset of generalized blistering by two years and in the other, no definite blister nor erosion was seen except for some appearing on the soles during the course of the disease. Western immunoblotting of EDTA-separated epidermal extracts revealed that the 230-kD bullous pemphigoid (BP) antigen was recognized by circulating autoantibodies in the patient sera, but the 180-kD BP antigen was not. The 180-kD BP antigen was recognized weakly by immunoblotting of the 180-kD BP antigen NC16a domain fusion protein, which shows high detection sensitivity. These findings suggested that weak reactivity of autoantibodies with either whole or a part of the 180-kD BP antigen molecule in some way accounts for negligible or localized blister-formation in this disorder. However, no particular change was noted in the reactivity with 180-kD BP antigen between the patient serum obtained before and after the development of generalized blistering. It is possible that different factors from the changes in serum reactivity with BP antigens may be involved in initiating generalized blistering.

Autoantibodies↗

Quercetin-induced melanogenesis in a reconstituted three-dimensional human epidermal model.

Quercetin (3,5,7,3',4'-pentahydroxyflavone) is one of the most abundant natural flavonoids. It is present in various common vegetables and fruits. In this report, we examined the effect of quercetin on melanogenesis using a three-dimensional reconstituted human epidermal culture model, MelanoDerm, which is a new commercially-available cultured human epidermis containing functional melanocytes. Treatment with 10 microM quercetin induced an increase of tyrosinase activity in cultured epidermis after 3-5 days in time-dependent manner. In the quercetin-treated epidermis, furthermore, melanin content and tyrosinase expression were markedly increased, as shown by immunohistochemistry after a 7-day culture period. Ultrastructural studies clearly indicated an accumulation of mature melanosomes (stages III and IV) inside the basal layer of the cultured epidermis after the quercetin treatment. In addition, the dendrites of melanocytes extended further towards the adjacent keratinocytes after quercetin treatment. These results suggest that quercetin has an effect on maturation of melanosomes and that quercetin has the potential to induced melanogenesis in human epidermis.

Culture Techniques↗

Nitric oxide inhibits ultraviolet B-induced murine keratinocyte apoptosis by regulating apoptotic signaling cascades.

Cytotoxic effects of nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) are considered to be one of the major causes of inflammatory diseases. On the other hand, protective effects of NO on toxic insults-induced cellular damage/apoptosis have been demonstrated recently. Ultraviolet B (UVB)-induced apoptosis of epidermal keratinocytes leads to skin inflammation and photoageing. However, it has not been elucidated what kind of effects NO has on UVB-induced keratinocyte apoptosis. Thus, in the present study, we investigated the problem and demonstrated that NO from NO donor suppressed UVB-induced apoptosis of murine keratinocytes. In addition, NO significantly suppressed activities of caspase 3, caspase 8 and caspase 9 that had been upregulated by UVB radiation. NO also suppressed p53 expression that had been upregulated by UVB radiation and upregulated Bcl-2 expression that had been down-regulated by UVB radiation. These findings suggested that NO might suppress UVB-induced keratinocyte apoptosis by regulating apoptotic signaling cascades in p53, Bcl-2, caspase3, caspase 8 and caspase 9.

Animals↗

420 nm intense continuous light therapy for acne.

BACKGROUND: Topical antibiotics, isotretinoin or systemic antibiotics are usually used for acne therapy. However, isotretinoin cannot be used during pregnancy because it can cause significant birth defects while systemic antibiotics can have adverse side effects such as gastrointestinal irritation, photosensitivity and tetracycline sensitivity. Describe here is a high-intensity, narrow-band, blue light (ClearLight) system, and its therapeutic clinical effect is investigated on acne using cutaneous measurements, bacterial observations and ultrastructural changes. MATERIALS AND METHODS: A total of 28 adult healthy volunteers with facial acne (mean age 28.1 years, range 16-56 years) were recruited for this study. They were treated with a total of eight serial biweekly 15-minute treatment sessions. Clinical counts of acne, as well as moisture, sebum and pH measurements were taken between each session. Nine of the 28 patients were followed for 2-3 months after the last treatment. Detection of bacteria in acne pustules was analyzed by culture and by polymerase chain reaction (PCR). Ultrastructural changes were examined in eight patients after four sessions of the light therapy. RESULTS: All patients completed the study. Overall, there was a 64.7% improvement in acne lesions. There were no bacterial changes before or after the therapy, although damaged Propionibacterium acnes were observed at the ultrastructural level. CONCLUSIONS: ClearLight performed eight times over 4 weeks can be useful in the treatment of acne. Further investigation will be needed to elucidate the mechanism of action of ClearLight.

Acne Vulgaris↗

Histological hair removal study by ruby or alexandrite laser with comparative study on the effects of wavelength and fluence.

BACKGROUND: Several different laser systems are currently used to remove unwanted hairs. In this study, we studied follicular changes following hair removal with ruby or alexandrite lasers at different fluences. METHODS: Unwanted hairs were treated with a ruby laser (Chromos 694, ICN PhotonIcs, UK) at 10, 14 or 18 J/cm2 or with an alexandrite laser (LPIR, Cynosure, USA) at 11, 14 or 17 J/cm2. A 3 mm skin punch biopsy was taken immediately after each laser exposure and also 1 month later. Specimens were stained for histological observation. They were observed using immunohistochemistry with antibodies recognizing factor VIII related antigen or PCNA, and also by the TUNEL method. Similarly, electron microscopic observation was examined. RESULTS: Immediately after the laser exposure, moderate follicular damage was observed following treatment with either type of laser. One month later, cystic formation of hair follicles and foreign body giant cells were observed in skin treated with either type of laser. A similar fluence with either laser treatment resulted in similar histological changes. CONCLUSION: In this study, the histological changes following treatment with a ruby or an alexandrite laser at the same fluence are similar.

Adult↗

Human airway trypsin-like protease induces PAR-2-mediated IL-8 release in psoriasis vulgaris.

Human airway trypsin-like protease (HAT), a novel serine protease in the airways, enhances cell growth and IL-8 production. The expression and role of HAT in the skin however, is unknown. Immunofluorescence staining and reverse transcription (RT)-PCR were done to know HAT production in normal and psoriatic tissues and keratinocyte cell lines. Cell growth and/or IL-8 release analyses were made by bromo-deoxyuridine (BrdU) uptake and ELISA. Psoriatic epidermis showed more extensive immunofluorescence expression of HAT, and less extensive expression of protease-activated receptor (PAR)-2. RT-PCR demonstrated a higher HAT and a lesser PAR-2 mRNA expressions in psoriatic epidermis. Normal keratinocyte and epidermoid carcinoma cell lines expressed HAT and PAR-2 mRNA, and immortalized keratinocytes (HaCaT) expressed PAR-2, but not HAT mRNA. PAR-2 was detected along the keratinocyte surface in culture and became invisible upon HAT stimulation, suggesting a process of its internalization. HAT or PAR-2 activating peptide did not enhance BrdU uptake, but induced an IL-8 release. Treatment with HAT and IL-1beta synergistically increased the effect of IL-8 release. Inhibition of PAR-2 resulted in a decreased HAT-induced IL-8 release. Thus, HAT might promote PAR-2-mediated IL-8 production to accumulate inflammatory cells in the epidermal layer of psoriasis.

Adult↗