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Akihiko Asahina

Publications and source records attributed to Akihiko Asahina.

At least 19 recordsLinked to original sources
PubMed2007

Treatment of 153 Japanese patients with Q-switched alexandrite laser.

We have recently used Q-switched alexandrite laser for the treatment of various kinds of pigmented skin lesions. We retrospectively compared therapeutic outcomes of 153 Japanese patients who consulted our department. This approach was not very efficient for nevus spilus/café-au-lait spots, which seemed laser-resistant, especially when the pigmentation had appeared after 1 year of age, was treated after 5 years of age, was located on the face, was oval with a smooth border, and the patient was male. This approach was equally effective for senile lentigo, nevus of Ota, and Mongolian spots, but less effective for acquired bilateral nevus of Ota-like macules. Some patients with sacral Mongolian spots or those with light-colored, senile lentigo developed severe post-inflammatory hyperpigmentation after treatment. As a whole, good therapeutic outcome was achieved after multiple treatment sessions. However, the use of other lasers or other treatment modalities should be considered to treat nevus spilus/café-au-lait spots.

Beryllium↗
PubMed2006

Role of Langerhans cells in cutaneous protective immunity: is the reappraisal necessary?

Langerhans cells (LC) are constantly exposed to external antigens and pathogens, and they are the cutaneous counterpart of dendritic cells (DC). DC not only act as professional antigen presenting cells to induce antigen-specific T cells for adaptive immune responses, but they also initiate a cascade of innate immune responses by sensing these danger signals. However, recent studies challenge the classical paradigm to position LC in the center of cutaneous immunity. Although LC express toll-like receptors (TLRs) that recognize bacterial and viral products, exposure to pathogen-associated TLR ligands triggers neither sufficient LC maturation nor good production of cytokines and chemokines. LC also lack the ability to produce IFN-gamma by any stimuli, and together with the characteristics of LC that are prone to produce Th2-type chemokines and to produce much less IL-12 in the presence of keratinocyte-derived GM-CSF, LC primarily may not have the character to induce Th1- and Tc1-type immune responses necessary for protective cellular immunity. Moreover, LC maturation is inhibited, rather than enhanced, by type I IFNs that are abundantly produced in viral infections in the skin microenvironment. Finally, recent data suggest that LC may not directly present viral antigens to T cells for their activation in mouse models of cutaneous viral infection. The alternative player in protective immune responses may be surrounding keratinocytes, which may modulate LC functions indirectly. Dermal DC may also participate in this scheme. Further studies are required to clarify the role of LC in their interplay with keratinocytes and other DC subsets, and to draw the entire picture of the cutaneous immune system against pathogens.

Animals↗
PubMed2006

Evaluation of the treatment of port-wine stains with the 595-nm long pulsed dye laser: a large prospective study in adult Japanese patients.

BACKGROUND: Treatments of port-wine stains with conventional pulsed dye laser yield inconsistent results. OBJECTIVE: We evaluated the efficacy and safety of the longer pulse duration 595-nm dye laser. METHODS: Sixty-six adult Japanese patients were enrolled in this prospective study. The laser treatment with a cooling device was repeated 4 times at 8-week intervals with a consistent setting of 10-ms pulse duration and an energy fluence of 12 J/cm2, using 7-mm spot size. RESULTS: Improvement of port-wine stains was observed after multiple treatments, and 67% of the patients achieved either good or excellent response after the fourth treatment. Transient purpura, edema, or both were noted immediately after each treatment (76%-79% and 58%-67%, respectively). Hyperpigmentation (8%-17%) and hypopigmentation (6%-14%) were also mild and their occurrence did not increase by repeating treatments. LIMITATIONS: Eighty five percent of the patients were classified as having Fitzpatrick skin type IV. CONCLUSION: Our study indicated that the 595-nm dye laser with 10-ms pulse duration may be effective and well tolerated in the treatment of port-wine stains in adult Asians.

Adult↗
PubMed2006

Necrolytic migratory erythema without glucagonoma in a patient with short bowel syndrome.

Necrolytic migratory erythema (NME) is an uncommon inflammatory dermatosis with a distinctive clinical and histological appearance. It shows irregular erythema, bullae, erosion, crusts and pigmentation. While it is typically associated with glucagonoma, some cases of NME without glucagonoma have been reported. Herein, we report a case of necrolytic migratory erythema associated with malabsorption 30 years after ileocolectomy. She presented erosive erythema with scale or partly flaccid bullae on her intergluteal cleft, buttock and extremities. Her laboratory data revealed essential amino acid deficiency and a slightly decreased serum zinc level, while her plasma glucagon level was low. With diagnosis of non-glucagonoma-associated NME with malabsorption due to short-bowel syndrome, she was treated and improved by i.v. amino acid supplement. Histological findings of NME include necrotic changes of keratinocytes in the upper epidermis, proliferation of those in the lower epidermis and inflammatory cell infiltration of upper dermis. We also examined the expression pattern of epidermal keratins (K6, K10) and Ki-67, one of the markers of proliferative activity, to assess the proliferation and differentiation of keratinocytes in a NME lesion by immunostaining. The findings with these immunostainings support the characteristics of HE-staining, and suggest hyponutrition may induce changing differentiation/proliferation of keratinocytes.

Cell Differentiation↗
PubMed2006

CCL28 production in HaCaT cells was mediated by different signal pathways from CCL27.

Both CCL27 and CCL28 are ligands for CCR10 and attract CCR10(+) lymphocytes. We previously demonstrated that CCL27 and CCL28 were strongly expressed in sera and lesional keratinocytes of patients with atopic dermatitis and psoriasis vulgaris. However, the regulation of CCL27 and CCL28 production in keratinocytes has not been well documented. In this study, we showed that CCL27 and CCL28 expression and production by a human keratinocyte cell line, HaCaT cells, were strongly induced by inflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta. CCL27 production was downregulated by inhibitors of p38 mitogen-activated protein kinase and nuclear factor-kappa B (NF-kappaB). By contrast, CCL28 production was downregulated by inhibitors of extracellular signal-regulated kinase and NF-kappaB. Our study results suggest that CCL28 produced by keratinocytes is mediated by different signal pathways from CCL27 and that both CCL27 and CCL28 are involved in the pathogenesis of inflammatory skin diseases.

Cell Line↗
PubMed2005

Signaling through CD40 ligand decreases CD80 expression on murine Langerhans cells and enhances IL-12 p40 production.

We previously showed that murine Langerhans cells (LC) express CD40 ligand (CD40L). In this study, we further investigated the function of CD40L on LC using agonistic antibodies and CD40L knockout (KO) mice. Signaling through CD40L decreased CD80 expression on LC 48 h after stimulation and the decrease was more remarkable in the presence of interferon-gamma (IFN-gamma). Signaling through CD40 enhanced the production of IL-12 p40 from LC, and simultaneous signaling through CD40L slightly augmented this effect. Addition of IFN-gamma further enhanced IL-12 p40 production. LC from CD40L KO mice expressed similar levels of surface molecules such as CD40, CD80, CD86, and MHC class II, compared with those from wild-type mice. However, they produced less amount of IL-12 p40 during 48 h after purification. These results suggest that signaling through CD40L on LC is important in regulating IL-12 production, which is critical for Th1 type immune responses.

Animals↗
PubMed2005

Differential production of Th1- and Th2-type chemokines by mouse Langerhans cells and splenic dendritic cells.

Some chemokines specifically attract T helper 1 (Th1) cells, whereas others attract T helper 2 (Th2) cells. In this study, we investigated the capacity of Langerhans cells (LC) to produce Th1- and Th2-type chemokines in comparison with that of splenic CD11c(+) dendritic cells (DC). We prepared highly purified (>95%) LC from BALB/c mouse skin using the panning method. With regard to Th1-type chemokines, exogenous stimulus, such as interferon-gamma (IFN-gamma), lipopolysaccharide, or polyinosinic-polycytidylic acid, was mandatory for the production of substantial amounts of CXCL10, CXCL9, and CXCL11 both in LC and splenic DC. LC, as a whole, exhibited low ability to produce Th1-type chemokines in comparison with splenic DC. As for Th2-type chemokines, LC, but not splenic DC, produced high levels of CCL22 and CCL17 constitutively during culture even without exogenous stimuli. The production of Th2-type chemokines was regulated in a complicated manner. In particular, interleukin-4 upregulated, and IFN-gamma downregulated both CCL22 and CCL17 production by LC. Of note, LC produced much more amounts of Th2-type chemokines than splenic DC under any conditions tested. Finally, Th1- and Th2-type chemokines produced by LC were shown to be functional using chemokine receptor-transfected-2B4 T cells. The high production of CC chemokine receptor 4 ligands by LC in the absence of IFN-gamma may be an important character discriminating LC from other DC.

Animals↗
PubMed2005

Type I interferons inhibit maturation and activation of mouse Langerhans cells.

Type I interferons (IFN) have an essential role in antiviral defense, and they are produced upon viral infection in a variety of cells. IFN-alpha/beta treatment of immature dendritic cells (DC) is known to induce their phenotypic and functional maturation, but it remains unclear whether stimulation by this cytokine family influences the functions and maturation of Langerhans cells (LC). We used highly enriched (>95%) LC directly isolated from BALB/c mouse skin and addressed this issue, comparing LC with splenic CD11c(+) DC. Type I IFN-treated LC exhibited impaired ability to produce IL-12 and inflammatory cytokines, IL-6 and TNF-alpha, whereas IL-10 production was not augmented. In splenic DC, the production of inflammatory cytokines was rather enhanced by type I IFN treatment. With regard to chemokines, in both LC and splenic DC, type I IFN upregulated the production of inflammatory chemokines, such as CXCL10, CXCL11, CCL3, CCL4, and CCL5. Strikingly, IFN-beta treatment reduced the expression of CD40, CD54, CD80, and CD86 on LC, whereas IFN-beta-treated splenic DC showed enhanced expression of these molecules. Furthermore, IFN-beta-treated LC had impaired costimulatory activity for anti-CD3-induced proliferation of T cells. Finally, treatment with IFN-alpha/beta reduced the migratory capacity of LC to CCL21. These results indicate that type I IFN inhibit maturation and activation of LC in a direct manner. Our observations may provide a novel explanation for the reported inability of LC to act as potent antigen-presenting cells in cutaneous and mucosal viral infection.

Animals↗
PubMed2005

Epithelioid sarcoma associated with lung adenocarcinoma.

Epithelioid sarcoma is an uncommon soft tissue malignancy which is often misdiagnosed as necrobiotic granuloma or chronic inflammation. Many patients have local recurrence and distant metastasis because of its infiltrating growth. We report a 49-year-old Japanese man who had an ulcer with surrounding erythema on the left forearm after he sustained a bruise on this spot. His mother and father had died of rectal and bladder carcinoma, respectively, and he had also had a seminoma previously. Therefore, there was familial accumulation of malignancies. A skin biopsy revealed polygonal, plump, or spindle-shaped epithelioid cells and lymphocytes infiltrating through the dermis. Immunohistochemical studies showed positive staining for cytokeratins, epithelial membrane antigen, CD34 and vimentin and negative staining for desmin, CD68, HHF-35, 1A4 and p53. These clinical and histological features were diagnostic of epithelioid sarcoma. CT scans detected nodules in the right lung. A lung biopsy revealed that he had well-differentiated adenocarcinoma which expressed p53. Mutations in the TP53 gene were not searched for. We selected conservative treatment because the patient did not want surgical wide resection or amputation. Therefore, radiation, thermotherapy, application of 0.5% doxorubicin hydrochloride ointment and right lower lobectomy with lymph node dissection were performed. The size of the ulcer and the tumor invasion along the fasciae of muscles were decreased, however, metastasis of the epithelioid sarcoma was detected in the lymph node of the left axilla four years after the diagnosis.

Adenocarcinoma↗
PubMed2005

Mycosis fungoides associated with intestinal mucosa-associated lymphoid tissue lymphoma.

Coexistence of cutaneous T-cell lymphoma (CTCL) and a B-cell malignancy is rare. We report a case of mycosis fungoides (MF) associated with intestinal mucosa-associated lymphoid tissue (MALT) lymphoma, which is a low-grade B-cell lymphoma of marginal cell origin. To the best of our knowledge, there have been only two cases of coexistent CTCL and MALT lymphoma, and this is the first case with typical MF and intestinal MALT lymphoma. The coexistence in our case might be coincidental, but genetic predisposition and the immunoregulatory capacity of neoplastic T lymphocytes may be factors contributing to this association.

Antigens, CD20↗
PubMed2004

Langerhans cells exhibit low responsiveness to double-stranded RNA.

Double-stranded RNA (dsRNA) is a viral product recognized by Toll-like receptor 3 (TLR3), and it is a potent activator of dendritic cells (DC). We compared Langerhans cells (LC) and splenic CD11c(+) DC and investigated the responsiveness to dsRNA. We prepared highly purified LC (> 95%) using the panning method. TLR3 mRNA was expressed in LC, splenic DC, and keratinocytes (KC). The expression of IFN-beta mRNA was enhanced in LC and splenic DC by Poly(I:C) stimulation. However, cytokine/chemokine production in response to Poly(I:C) by LC was much lower than that by splenic DC. In addition, Poly(I:C) induced further maturation in splenic DC, but not in LC. Finally, we found that the mouse KC cell line, PAM212, produced a great amount of IL-1alpha by Poly(I:C) stimulation, and that IL-1alpha promoted the maturation of LC. These data altogether indicate that LC exhibit low responsiveness to dsRNA. It is possible that KC may primarily trigger anti-viral immune responses in the skin via cytokine production such as IL-1alpha.

Animals↗