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Biomedical subjects

Fukumi Furukawa

Publications and source records attributed to Fukumi Furukawa.

At least 19 recordsLinked to original sources
PubMed2006

Cyclophosphamide enhances TNF-alpha-induced apoptotic cell death in murine vascular endothelial cell.

Cyclophosphamide (CPA) is one of the therapeutic agents for systemic inflammatory disorders. In murine dermal endothelial cells (F-2), 4-hydroxycyclophosphamide (4-HC), which is active metabolite of CPA, enhanced TNF-alpha-induced DNA fragmentation. In addition, 4-HC was shown to elevate TNF-alpha-induced caspase-3 activation. Caspase-8 activation was identified by the treatment of TNF-alpha, whereas 4-HC was no effect. In contrast, only when treated with 4-HC, caspase-9 activation and the increase in the intracellular expression of Bax were detected. These results suggest that CPA may sensitize endothelial cells to TNF-alpha-induced apoptosis through a mitochondria-dependent pathway and clinically may contribute to the limitation of inflammatory process.

Animals↗
PubMed2006

Effects of alpha-hydroxy acids on the human skin of Japanese subjects: the rationale for chemical peeling.

Alpha-hydroxy acid (AHA) agents, such as glycolic acid and lactic acid, have been used as therapeutic agents for more than a quarter of a century. Recently, they have been used as agents to rejuvenate photo-aged skin. It is believed that these AHA agents induce the epidermis to remodel and accelerate desquamation, thus exerting their therapeutic effects. In this study, we investigated the histological differences in skin treated with glycolic, lactic, citric and acetic acids once daily for 6 weeks. The melanin pigments in the basal layer were less prominent in the glycolic and lactic acid-treated skin than in the citric and acetic acid-treated skin. The melanin deposits in the horny layers were equal for all AHA. However, the melanin deposits in the squamous layers were less prominent in the glycolic and lactic acid-treated skins than in the citric and acetic acid-treated skins; this was analogous to observations of the basal layers. Collagen I and procollagen I were increased after treatment with glycolic, lactic and citric acid in the upper dermis, but were not increased with acetic acid treatment. However, the staining of the epidermis and dermis for matrix metalloproteinase-1 (MMP-1) after treatment was not significantly different among the agents. Our data suggest that longer treatment intervals with glycolic and lactic acid can cause improvements in both the epidermal and dermal components and support the usefulness of AHA for rejuvenating photo-damaged skin.

Acetic Acid↗
PubMed2006

Recent advances in chemical peeling in Japan.

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or aesthetic improvement. This treatment consists of the application of one or more chemical agents to the skin. Recently in Japan, chemical peeling has been very popular for medical as well as aesthetic treatment. Because the scientific background and an adequate approach have not been completely established, medical and social problems have been reported. To address these issues, the Japanese Dermatological Association has established standard guidelines for chemical peeling, and the scientific background and validity of chemical peeling has been assessed. In this review, a set of guidelines for chemical peeling is introduced, and we will discuss several clinical and histological studies including the effects of glycolic acid, and the application of deer peeling to skin tumors in our department.

Chemexfoliation↗
PubMed2006

Recessive dystrophic epidermolysis bullosa: case of non-Hallopeau-Siemens variant with premature termination codons in both alleles.

Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the COL7A1 gene encoding collagen, the major component of anchoring fibrils. Premature termination codon (PTC) mutations in both alleles usually lead to the Hallopeau-Siemens variant that shows the most severe phenotype. We experienced a case of the non-Hallopeau-Siemens variant (nHS-RDEB), which had a mild clinical severity although it has PTC mutations in both alleles. Our patient was a compound heterozygote for a nonsense mutation (R669X) in exon 15 and a nonsense mutation (E2857X) in exon 116. But we confirmed the existence of some anchoring fibrils on electron micrograph. This suggested that a PTC close to the 3' end of COL7A1 does not completely abolish the collagen VII mRNA. We hypothesized that the truncated procollagen VII from the mutant allele with a nonsense mutation (E2857X) in exon 116 included two out of eight cysteines needed for disulfide bond formation, and hence a few functional anchoring fibrils could be formed.

Adult↗
PubMed2005

Animal models of spontaneous and drug-induced cutaneous lupus erythematosus.

Skin lesions are one of the most common manifestations of lupus erythematosus (LE) disorders such as systemic LE and discoid LE. The etiology of cutaneous LE is not fully understood. To address this issue, appropriate animal models frequently clarify the etiology and pathogenesis of autoimmune diseases, although no single animal model perfectly mimics a human disease. A common dermatological finding in many SLE-prone mouse strains is the deposition of immunoglobulins at the dermoepidermal junction. Over the past decade, the most exciting and important finding has been the discovery of the Fas-defect in the pathogenesis of the autoimmune MRL/lpr mouse, which is a good model for the spontaneous development of skin lesions similar to those seen in human LE. The analysis of MRL/lpr mice showed a close association between immunoglobulin deposits and the appearance of skin lesions. Transgenic and knock out mice have advanced the investigation of cutaneous LE. Furthermore, the model of drug-induced cutaneous LE can yield additional insight since the trigger is clear in drug-induced LE. Cutaneous LE lesions can also be induced in TCRalpha-/- mice treated with fluorouracil and ultraviolet B light irradiation. Studies on both spontaneous and experimental models will elucidate the pathogenesis of complicated and multifactorial cutaneous LE.

Animals↗
PubMed2004

Brooke-Spiegler syndrome associated with cylindroma, trichoepithelioma, spiradenoma, and syringoma.

Brooke-Spiegler syndrome is a rare, autosomally dominant disease characterized by the development of multiple cylindromas, trichoepitheliomas, and occasional spiradenomas. We report herein a case of Brooke-Spiegler syndrome in a 55-year-old woman associated with multiple cylindromas, spiradenomas, trichoepitheliomas, and syringomas that developed on her face. Her 52-year-old sister also suffered from multiple trichoepitheliomas. Although there is variable clinical and histological expression in Brooke-Spiegler syndrome, all of the tumors encountered in our case were related to folliculosebaceous-apocrine units.

Biopsy, Needle↗
PubMed2004

A case of symmetrical leukemia cutis on the eyelids complicated by B-cell chronic lymphocytic lymphoma.

We describe herein a case of symmetrical bilateral leukemia cutis on the eyelids, especially on the lower lids, in a patient with B-cell chronic lymphocytic leukemia (CLL). The patient was a 63-year-old Japanese man who had been diagnosed with CLL. Eyelid swelling is well known to result from local skin or systemic diseases including tumors, hyperthyroidism, nephritic syndrome, and hypoalbuminemia. To our knowledge, symmetrical, bilateral, flesh-colored leukemia cutis on the eyelids has not been previously reported.

Biopsy, Needle↗
PubMed2004

Dosage and adverse effects of topical tacrolimus and steroids in daily management of atopic dermatitis.

Since 1999, combination therapy with tacrolimus and topical steroids has been widely used for the treatment of adolescent/adult-type atopic dermatitis. In order to determine the clinical doses of topical tacrolimus and steroids for daily treatment of atopic dermatitis and to elucidate their beneficial and adverse effects, we analyzed the clinical data from 215 patients with atopic dermatitis who were more than 16 years old. Less than 70 g of tacrolimus and less than 15 g of steroids were applied to 90% of the patients on the face and neck, and less than 75.8 g of tacrolimus and less than 322 g of steroids were applied to 90% of the patients on the trunk and extremities during the six-month treatment period. Topical tacrolimus is much more frequently used on face and neck lesions (99.1%); in only 39.5% of cases was it used on the trunk and extremities. The majority of patients improved after six months of the combination topical therapy; however, atopic dermatitis was not controlled in 6% of the patients. The combination therapy did not seem to increase the risk of cutaneous infections; however, the incidence of herpes simplex infection on the face and neck was 2.8% at pre-treatment and slightly increased to 4.7% during the therapy. The incidence of all steroid-induced adverse effects was reduced both in frequency and intensity with a decrease in the dose of topical steroids through simultaneous tacrolimus application. Combination therapy with topical tacrolimus and steroids is useful for treating atopic dermatitis, but a small percentage of the patients still cannot be satisfactorily treated. For such patients, adjustments of the dose and rank of topical steroids and tacrolimus and other therapeutic adjuncts are necessary.

Administration, Cutaneous↗
PubMed2003

Photosensitivity in cutaneous lupus erythematosus: lessons from mice and men.

Mouse models are similar but not identical to human diseases. However, they are important for research into the pathogenesis underlying autoimmune diseases because they allow us to evaluate similarities and differences between human diseases and mouse models. In fact, experimental models and inbred lupus-prone mice are tools that enable a better understanding of the 'photosensitivity' or 'photocytotoxicity' phenomena in relation to autoimmunity. Genetic studies of MRL/lpr mice revealed that the appearance of macroscopic lupus erythematosus (LE)-like skin lesions needs the lpr mutation plus an additional factor in an autosomal dominant fashion. The candidate is ultraviolet (UV) B light, the susceptibility to which is regulated by the genetic background. Such a genetic background is also speculated to be important in human cutaneous LE patients. The translocation of anti-SS-A/Ro on cultured keratinocytes irradiated with UVB light is quantitatively different from photocytotoxicity, and the quantitative levels are significantly higher in systemic LE and subacute cutaneous LE than in discoid LE and normal controls. This review focuses on the lessons gleaned from mouse and human models, and discusses photosensitivity in human cutaneous LE.

Animals↗
PubMed2003

A rare case of autoimmune polyglandular syndrome type 3.

A 57-year-old female was admitted to our hospital suffering from a lower lip tumor, small ulcers in the arms and alopecia of the head. Because she had type 2 diabetes mellitus (DM) for the past 3 years, she was referred to our department of internal medicine for its treatment. Her endogenous insulin secretion was much decreased despite the short duration of diabetes. Glutamic acid decarboxylase antibodies (GADA) and islet cell antibodies (ICA) were both positive. Therefore, she was diagnosed as having slowly progressive form of type 1 DM. Type 1 DM is sometimes complicated with autoimmune disorders. After further examinations, she was diagnosed as having Sjögren's syndrome, Graves' disease and autoimmune neutropenia (AIN). According to the histological examinations of the lip tumor and peripheral site of the skin ulcer, the patient was diagnosed as having carcinoma spinocellulare and chronic cutaneous lupus erythematosus. The examination also showed positive anti-intrinsic factor and anti-ribonucleoprotein (RNP) antibodies. She is a rare case of an autoimmune polyglandullar syndrome (APS) type 3 simultaneously manifesting these seven diseases with multiple autoimmune antibodies.

Alopecia↗
PubMed2003

Vaccine therapy for cutaneous T-cell lymphoma.

We demonstrated that percutaneous peptide immunization by way of skin with impaired barrier function is a simple and noninvasive strategy to generate effective immune responses against tumors. This therapeutic strategy seems to be beneficial for the treatment of skin-associated malignancies, including CTCL, because specific CTLs are considered to be well-induced in lymph nodes that neighbor barrier-disrupted skin (Fig. 3). There remain unsolved issues concerning (1) the ability of cytokines and growth factors to enhance efficacy of this therapy and (2) the time schedule of clinical trials. It was recently shown that application of antigenic protein or its coding DNA to skin with increased permeability yields antigen-specific antibody responses. Because the skin represents an easily accessible site for immunization and vaccination, percutaneous immunization using corneum barrier-disrupted skin is an alternative to injection of CTL-inducing molecules and can readily be exploited for cancer treatment in humans. The effective induction of CTLs suggests that the method that uses barrier-disrupted skin can potentially be applied to treatments of virus and helminth infections with the use of certain antigenic peptides.

Animals↗
PubMed2003

P-cadherin expression in skin peeled with phenol or trichloroacetic acid (TCA).

P-cadherin expression patterns were studied in trichloroacetic acid (TCA) or phenol treated skin. The expression was absent or very weak on the basal cell surfaces by day 2. Seven days after peeling, P-cadherin was clearly distributed in a continuous granular pattern over the cell surface of the entire epidermis of the 40% TCA treated skin, in a weak granular pattern on a few suprabasal cells and basal cells of the phenol treated skin, and very weakly expressed on the lateral surfaces and in the cytoplasm of basal cells of the 60% TCA treated skin. Based on the present results and previous reports, it is likely that there are distinct patterns of P cadherin expression. Furthermore, a specific type of P cadherin expression might be involved in wound healing in general, which could provide new insights into tissue repair mechanisms after chemical peeling.

Adult↗