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Biomedical subjects

M Morohashi

Publications and source records attributed to M Morohashi.

At least 19 recordsLinked to original sources
PubMed2006

Procyanidin oligomers counteract TGF-beta1- and TGF-beta2-induced apoptosis in hair epithelial cells: an insight into their mechanisms.

Procyanidin oligomers are polyphenol compounds we have identified in apples and barley which have hair growth stimulant effects, and which are able to promote hair epithelial cell growth and induce anagen induction of the hair cycle in the in vivo murine model. For the purpose of examining the hair-growing mechanisms of procyanidin oligomers, we examined their relationship to the TGF-beta signal pathway, known to be a regulator of catagen induction, and the mitogen-activated protein kinase cascade linked to cell proliferation. Addition of TGF-beta(1) or TGF-beta(2) to hair epithelial cell cultures dose-dependently decreased cell growth and induced apoptosis; however, addition of procyanidin B-2 to the culture neutralized the growth-inhibiting effects of both TGF-beta(1) and TGF-beta(2) and protected the cells from apoptosis. The same effects were observed with procyanidin B-3. We confirmed that procyanidin B-2 upregulates the expression of MEK-1/2 in cultured murine hair epithelial cells. We speculate that the hair-growing activity of procyanidin oligomers is at least linked to their growth-promoting effects on hair epithelial cells that follow MEK activation and their protective action on TGF-beta(1)- or TGF-beta(2)-induced apoptosis that is assumed to trigger catagen induction in the hair cycle.

Animals↗
PubMed2005

Aberrantly differentiated cells in benign pilomatrixoma reflect the normal hair follicle: immunohistochemical analysis of Ca-binding S100A2, S100A3 and S100A6 proteins.

BACKGROUND: Pilomatrixoma is a common benign cutaneous tumour containing differentiated hair matrix cells. This tumour is mainly composed of basophilic, transitional, shadow and squamoid cells. Although some S100 proteins are expressed in a tissue-specific manner in the hair follicle (e.g. S100A2 in the outer root sheath, S100A3 in the cortex and cuticle, and S100A6 in the inner root sheath), little information is available concerning their distribution in the aberrantly differentiated tissues of pilomatrixoma. OBJECTIVES: To characterize the disordered epithelial elements of pilomatrixoma by localizing S100A2, S100A3 and S100A6 proteins. METHODS: Immunohistochemistry and dual-immunofluorescence microscopy were performed on 22 pilomatrixoma specimens using antibodies specific to the three proteins. RESULTS: Tissue-specific distribution of the S100 proteins investigated was preserved in the morphologically disordered tumour tissues. Anti-S100A2 antibody stained squamoid cells and putative outer root sheath cells; basophilic and potential hair matrix cells were occasionally stained. S100A3 staining was found in transitional cells and putative cortical cells, and was strong in both dispersed cells and hair-like structures surrounding cells which were presumably cuticular cells. Anti-S100A6 antibody labelled some S100A3-negative transitional cell strands, potentially inner root sheath cells. CONCLUSIONS: The epithelial elements of pilomatrixoma can be characterized using S100 proteins as biochemical markers. Our results show that pilomatrixomas retain a certain degree of differentiation indicative of distinct hair-forming cells.

Basophils↗
PubMed2005

Characteristic alterations of cutaneous neurogenic factors in photoaged skin.

BACKGROUND: Although it has been recognized that photoageing and chronological ageing differ in various morphological and biological aspects, the characteristic alterations of cutaneous neurogenic factors in photoaged skin are poorly characterized. OBJECTIVES: To characterize cutaneous neurogenic factors, including innervation, neuropeptides, nerve growth factor and interactions of mast cells, in photoaged skin. SUBJECTS AND METHODS: Paired biopsy specimens were obtained from sun-exposed volar forearm skin and from sun-protected dorsal upper arm skin of 20 elderly subjects. Various cutaneous neurogenic factors, including innervation, neuropeptides, neurokinin receptor, nerve growth factor, neurogenic inflammation and morphology of mast cells, were compared in sun-exposed vs. sun-protected skin quantitatively and qualitatively. RESULTS: Cutaneous neurogenic factors associated with photoageing were characterized by a significant increase in the densities of dermal and intraepidermal nerve fibres, a correlation between epidermal innervation and the severity of photodamage, increases in the number of neuropeptidergic sensory nerve fibres in the dermis and in tissue levels of sensory neuropeptides, increases in the content of nerve growth factor, reduced expression of neurokinin receptor 1 by epidermal keratinocytes and by vascular endothelial cells and a tachykinin-specific reduction of cutaneous neurogenic inflammation. Mast cells in photodamaged skin showed several characteristic morphological features, including various degrees of activation and an intimate association with fibroblasts, which were distinct from those in sun-protected skin. Furthermore, mast cells in photodamaged skin possessed larger amounts of substance P within their granules than did those in sun-protected skin. CONCLUSIONS: These findings document for the first time characteristic alterations of cutaneous neurogenic factors in photodamaged skin and suggest that the cutaneous nervous system may be involved in photoageing processes.

Aged↗
PubMed2003

Pruritogenic mediators in psoriasis vulgaris: comparative evaluation of itch-associated cutaneous factors.

BACKGROUND: Although some patients with psoriasis vulgaris also complain of severe pruritus, the data available regarding pruritus in psoriasis are sparse. OBJECTIVES: To clarify the mechanism and mediators involved in the pruritus of psoriasis vulgaris, we compared itch-associated factors in lesional skin from psoriatic patients vs. skin without pruritus quantitatively using a panel of histological and immunohistological parameters. PATIENTS AND METHODS: Biopsied specimens were obtained from 38 patients with psoriasis vulgaris who were divided into two groups according to the presence or absence of pruritus. RESULTS: When compared with psoriatic patients devoid of pruritus, lesional skin from patients with pruritus showed the following characteristic features: (i) a rich innervation both in the epidermis and in the papillary dermis; (ii) an increase in neuropeptide substance P-containing nerve fibres in perivascular areas; (iii) decreased expression of neutral endopeptidase in the epidermal basal layer as well as in the endothelia of blood vessels; (iv) many mast cells showing degranulating processes in the papillary dermis; (v) a strong immunoreactivity for nerve growth factor (NGF) throughout the entire epidermis and an increased NGF content in lesional skin homogenates; (vi) an increase in the expression of high-affinity receptors for NGF (Trk A) in basal keratinocytes and in dermal nerves; (vii) an increased population of interleukin-2-immunoreactive lymphocytes; and (viii) a strong expression of E-selectin on vascular endothelial cells. A significant correlation was observed between the severity of pruritus and protein gene product 9.5-immunoreactive intraepidermal nerve fibres, NGF-immunoreactive keratinocytes, expression of Trk A in the epidermis and the density of immunoreactive vessels for E-selectin. These findings indicate that possible pruritogenic mediators in psoriatic lesional skin are neurogenic factors including innervation, neuropeptide substance P, neuropeptide-degrading enzymes and NGF, activated mast cells, one or more cytokines and endothelial-leucocyte adhesion molecules. CONCLUSIONS: These data document for the first time itch-related local markers in psoriasis, and suggest complex and multifactorial mechanisms of pruritus in the disease. These results provide the groundwork for further studies to evaluate the efficacy of antipruritic treatment for psoriatic patients.

Adult↗
PubMed2003

Developmental changes in interleukin-12-producing ability by monocytes and their relevance to allergic diseases.

BACKGROUND: The T helper type-2 (Th2)-dominated situation can be observed in allergic diseases such as asthma or atopic dermatitis. A reduced ability to produce IL-12, which is a key cytokine for the induction of Th1 responses, has been proposed to lead to aberrant Th2 development in these disease conditions. OBJECTIVE: This study was intended to examine how IL-12-producing ability might associate with allergic diseases as a function of age. METHODS: IL-12 production by monocytes at various ages was assessed in patients with bronchial asthma and/or atopic dermatitis (n = 100) in comparison with non-allergic control subjects (n = 144). Whole blood cells were stimulated with lipopolysaccharide (LPS) after priming with IFN-gamma, then intracellular cytokine expression of IL-12 and IL-8 as a control cytokine of CD14-positive cells was assessed by flow cytometric analysis. RESULTS: In the control subjects, the ability of monocytes to produce IL-12 was negligible at birth and gradually increased with advancing age, whereas IL-8 production was intense throughout the human life. At more than 7 years of age, IL-12 production of patients with allergic diseases was significantly lower compared with that of control subjects. The unexpected finding was that infants and children below 6 years of age with allergic diseases tended to produce more IL-12 compared with age-matched controls. In this young group, it was noted that enhanced IL-12 production by monocytes was especially observed in allergic patients with specific IgE antibodies against some food allergens. Significant inverse relationships between serum IgE levels and IL-12-producing ability were found in the teenage and adult groups, but not in the younger children. CONCLUSION: IL-12 appeared to play different roles in the pathogenesis of allergic diseases between younger and older ages.

Adolescent↗
PubMed2003

Localization and content of nerve growth factor in peripheral blood eosinophils of atopic dermatitis patients.

BACKGROUND: Atopic dermatitis (AD) is a chronic and relapsing eczematous skin disorder characterized by eosinophilia. Nerve growth factor (NGF) modulates the allergic response through interactions with immune-inflammatory cells. Eosinophils have been reported to store NGF as a preformed mediator. OBJECTIVE: To gain further insight into the significance of eosinophils in association with NGF in the pathogenesis of AD, the localization of NGF within eosinophils and the difference of the eosinophil-derived NGF content in the peripheral blood of normal volunteers vs. AD patients were investigated. METHODS: We examined the localization of NGF within human eosinophils using the post-embedding immunoelectron microscopy and compared NGF content in freshly isolated eosinophil sonicates from the peripheral blood of 31 normal volunteers vs. 42 AD patients by immunoenzymatic assay. A possible correlation between the levels of NGF and major basic protein was also examined. RESULTS: Immunoelectron microscopic studies revealed that NGF was localized in the central core of normal eosinophil granules, where major basic protein is also present as a preformed mediator, in homogeneous granules and in intergranular ductal or vesicular structures adjacent to specific granules of eosinophils. NGF content in eosinophils was significantly increased in AD patients. Furthermore, there was a significant correlation between levels of NGF and major basic protein in eosinophils of AD patients. CONCLUSIONS: Increased levels of NGF contained in eosinophils of the peripheral blood from AD patients, when released with other mediators such as basic proteins, could promote inflammation and local tissue damage.

Adult↗
PubMed2003

Secondary infections with beta-hemolytic streptococci in skin lesions.

Secondary infections (SI) in skin lesions are common. In the present study 40 beta-hemolytic streptococci were isolated from 36 patients suffering from SI due to various skin diseases. Staphylococcus aureus coexisted with beta-hemolytic streptococci in 29 of these cases (81%), and beta-hemolytic streptococci were often associated with coagulase-negative staphylococci and gram-positive rods. Eighteen patients (50%) carried beta-hemolytic streptococci predominantly. In most cases of SI due to atopic dermatitis (AD), the predominant species was S. aureus, while in other skin diseases, S. aureus and beta-haemolytica streptococci were predominant in approximately 50% of the patients, except for SI due to tumors and viral diseases. The mean age of patients with SI and beta-hemolytic streptococci was 37 years and that of patients with SI and predominant S. aureus was 32 years. The lower mean age found for S. aureus was due to SI found in patients with AD. This study emphasizes the polymicrobial microbiology of SI.

Adolescent↗
PubMed2003

Characteristics of anaerobes from skin specimens.

Anaerobes isolated from skin specimens from 1999 to 2001 were examined. The most common type was Peptostreptococcus spp., especially P. magnus and P. assaccharolyticus and Bacteroides fragilis. Dominance was seen for P. magnus, P. acnes and P. prevotii. Peptostreptococcus spp. and P. acnes showed high susceptibility to four antimicrobial agents. Prevotella spp. and B. fragilis showed low or no susceptibility to ampicillin, while B. fragilis showed low susceptibility to ceftizoxime. Evaluation of anaerobes is important for the balance of skin flora as well as for the choice of antimicrobial agents, when the anaerobes are pathogenic.

Adolescent↗
PubMed2003

Propionibacterium acnes lipase in seborrheic dermatitis and other skin diseases and Unsei-in.

We examined Propionibacterium acnes lipase in skin diseases and Unsei-in. Butyric acid production in axillary seborrheic dermatitis (ASD) was higher than in other dermatitis, and that in acne vulgaris (AV) was significantly higher than in controls. P. acnes lipase is the pathogenic factor in AV and fatty acids produced by lipase might be the pathogenic factor in ASD. Unsei-in suppressed P. acnes lipase probably because some ingredients have antimicrobial and anti-inflammatory activities.

Adult↗
PubMed2002

Sebaceous glands in acne patients express high levels of neutral endopeptidase.

Acne is a complex, chronic and common skin disorder of pilosebaceous units. Although it is known that exacerbation of acne results from emotional stress, the nature of the association between stress and acne remains unclear. This is due in part to the lack of substantial evidence regarding the participation of cutaneous neurogenic factors in the pathogenesis of acne. To examine the possible involvement of neurogenic factors in the etiology of acne, we used immunohistochemistry to compare the distribution of SP-containing nerve fibers around sebaceous glands and the expression of neutral endopeptidase in sebaceous acini of the facial skin of acne patients and of healthy subjects. More numerous substance P immunoreactive nerve fibers in close apposition to the sebaceous glands and an increase in expression of neutral endopeptidase in sebaceous acini were observed in acne patients compared with the controls. Immunoelectron microscopy revealed that the subcellular localization of neutral endopeptidase was restricted to the Golgi apparatus and the endoplasmic reticulum within sebaceous germinative cells. In addition, in vitro experiments using an organ culture system demonstrated that substance P induced expression of neutral endopeptidase in sebaceous glands in a dose dependent manner. This study reveals that substance P and its degrading enzymes are involved in the pathogenesis of acne, which in turn might partially explain the pathologic significance of neurogenic and psychogenic aspects in the disease process.

Acne Vulgaris↗
PubMed2002

Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis.

BACKGROUND: Neurogenic components, such as neurotrophic factors and neuropeptides, are probably involved in the pathogenesis of atopic dermatitis (AD) via the neuroimmunocutaneous system. Numerous in vitro and in vivo studies have shown that nerve growth factor (NGF), the best-characterized member of the neurotrophin family, modulates the synthesis of the neuropeptide substance P (SP), both of which may be associated with the pathogenesis of human allergic diseases. OBJECTIVES: To evaluate the levels of NGF and SP in the plasma of patients with AD and to examine their possible correlation with disease activity. METHODS: We measured plasma levels of NGF by an immunoenzymatic assay and of SP by aradioimmunoassay in 52 patients with AD, and compared them with 35 normal non-atopic controls. The severity of the disease in AD patients was evaluated using validated clinical scoring systems. RESULTS: Patients with AD had significant increases in plasma levels of NGF and SP compared with controls (P < 0.0005 and P < 0.0001, respectively). A positive correlation between the plasma levels of NGF and SP was found in AD patients (correlation coefficient, Cc = 0.920, P < 0.0001). There was a significant correlation of plasma NGF and SP levels with disease activity evaluated using three different scoring systems: the grading system of Rajka and Langeland (P < 0.001 and P < 0.01, respectively), the objective Severity Scoring of AD (Cc = 0.656, P < 0.005 and Cc = 0.752, P < 0.0005, respectively) and the Eczema Area and Severity Index (Cc = 0.740, P < 0.001 and Cc = 0.765, P < 0.005, respectively). CONCLUSIONS: These data represent the first reported evidence of increased plasma levels of NGF and SP in an allergic human skin disease. They suggest that these neurogenic factors systemically modulate the allergic response in AD, probably through interactions with cells of the immune-inflammatory component. In addition, NGF and SP may be useful markers of disease activity in patients with AD.

Adolescent↗
PubMed2002

Isolation of Enterococcus species from infectious skin lesions.

Enterococcus faecalis was isolated at a frequency of 70% and was chiefly isolated from secondary infections due to ulcer/decubitus. Seven sole/predominant E. faecalis were isolated. Penicillins were more effective against E. faecalis and the sensitivities of E. faecalis to antimicrobials were higher than those of E. faecium. Some nonpredominant E. faecalis strains were sensitive to erythromycin probably due to less resistant mechanisms. The characterization of Enterococcus spp. is especially important when choosing appropriate antimicrobials for therapy.

Anti-Bacterial Agents↗
PubMed2002

Various Streptococcus species isolated from infectious skin diseases.

An evaluation was carried out of the types of Streptococcus spp. (excluding Streptococcus pyogenes) isolated from infectious skin diseases, and their susceptibilities to eight antimicrobial drugs of the Streptococcus spp. isolated. The types of diseases were also evaluated. A total of 29 Streptococcus spp. were identified and Streptococcus agalactiae was the most common. Streptococcus spp. were found to be susceptible to the eight antimicrobials used except gentamicin; susceptibility to gentamicin varied according to species. Susceptibility to beta-lactams was 100% and this drug should be considered the antimicrobial of choice in Streptococcus spp. treatment.

Anti-Bacterial Agents↗
PubMed2002

Seijo-bofu-to, Jumi-haidoku-to and Toki-shakuyaku-san suppress rashes and incidental symptoms in acne patients.

Seijyo-bofu-to, Jumi-haidoku-to and Toki-shakuyaku-san effectively suppressed acne rashes as well as incidental symptoms. The synergistic activities of the ingredients in the Kampo formulations might produce these effects. In contrast, distinct suppression of incidental symptoms was not found with antimicrobials. The cause of adverse effects in antimicrobials has not yet been clarified and different degrees of suppression of incidental symptoms among the Kampo formulations exist.

Acne Vulgaris↗
PubMed2001

Hornerin, a novel profilaggrin-like protein and differentiation-specific marker isolated from mouse skin.

A novel mouse cDNA named hornerin was isolated by RNA differential display applied to developing mouse skin. Hornerin, which has 2,496 amino acids, comprises EF-hand domains at the N terminus followed by a spacer sequence and a large repetitive domain, indicating that hornerin is a novel member of the "fused gene"-type cornified envelope precursor protein family. The repetitive domain of hornerin was found to be rich in glycine, serine, and glutamine. Hornerin was expressed in the tongue, esophagus, forestomach, and skin among the adult mouse tissues examined, all of them cornifying stratified epithelium. In the embryonic mouse skin, hornerin mRNA was first detected on gestational day 15.5 in the epidermis coincidentally with the formation of a granular layer. In accordance with this, hornerin was detected in the granular and cornified layers of the mature epidermis. In the granular cells of the epidermis, the hornerin protein was detected in keratohyalin granules together with profilaggrin. Furthermore, Western blot analysis of the mouse skin showed that the hornerin protein was cleaved during the process of epidermal differentiation, indicating possible posttranslational proteolytic processing as is observed in profilaggrin. Differentiation of primary mouse epidermal keratinocytes with 0.12 mm Ca(2+) resulted in the induction of hornerin. These results indicate that hornerin is structurally as well as functionally most similar to profilaggrin among the family members and possibly plays pleiotropic roles, including a role in cornification.

Amino Acid Sequence↗
PubMed2001

Quantitative analysis of the proliferation of epidermal cells using a human skin organ culture system and the effect of DbcAMP using markers of proliferation (BrdU, Ki-67, PCNA).

The process of re-epithelialization of a wound in the epidermis comprises the following steps: proliferation of epidermal basal cells, migration of epidermal cells to the wound surface, and cell differentiation. In the present study, we evaluated the proliferation of epidermal basal cells, an important process in wound healing, in the wound margin using a human skin organ culture system and immunohistochemical labeling with bromodeoxyuridine (BrdU), Ki-67, and proliferating cell nuclear antigen (PCNA), as markers of cell proliferation. Dibutyryl cyclic adenosine monophosphate (DbcAMP) is a derivative of cAMP and has been shown to modulate human keratinocyte proliferation. The proliferation of keratinocytes was promoted by DbcAMP and particularly strong effects in terms of BrdU labeling index, Ki-67-positive ratio, and PCNA-positive ratio, were seen at 10(-5) M. The skin organ culture system presented here uses adult preputial skin and is a simple technique that uses easily available materials. In addition to identifying S phase cells using BrdU as an index of cell proliferation, the immunohistochemical method for evaluating the expression of Ki-67 and PCNA is very simple. Accordingly, the method described here seems to be useful for evaluating cell dynamics in wound healing.

Biomarkers↗
PubMed2001

Pathogenesis of acne.

Acne vulgaris is a skin disorder of the sebaceous follicles that commonly occurs in adolescence and in young adulthood. The major pathogenic factors involved are hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation. The clinical presentation of acne can range from a mild comedonal form to severe inflammatory cystic acne of the face, chest, and back. At the ultrastructural level, follicular keratinocytes in comedones can be seen to possess increased numbers of desmosomes and tonofilaments, which result in ductal hypercornification. The increased activity of sebaceous glands elicited by androgen causes proliferation of P. acnes, an anaerobe present within the retained sebum in the pilosebaceous ducts. The organism possesses a ribosome-rich cytoplasm and a relatively thick cell wall, and produces several biologically active mediators that may contribute to inflammation, for instance, by promoting leukocyte migration and follicular rupture. In inflamed lesions, numerous neutrophils and macrophages infiltrate around hair follicles and sometimes phagocytose P. acnes. To examine the participation of neurogenic factors in the pathogenesis of acne, we quantitatively assessed the effects of neuropeptides on the morphology of sebaceous glands in vitro using electron microscopy. Substance P, which can be elicited by stress, promoted the development of cytoplasmic organelles in sebaceous cells, stimulated sebaceous germinative cells, and induced significant increases in the area of sebaceous glands. It also increased the size of individual sebaceous cells and the number of sebum vacuoles for each differentiated sebaceous cell, all of which suggests that substance P promotes both the proliferation and the differentiation of sebaceous glands. In this review, we introduce the general concept of pathogenic factors involved in acne, including typical electron microscopic findings and recent evidence of stress-induced exacerbation of acne from a neurological point of view. An improved understanding of the pathogenesis of acne should lead to a rational therapy to successfully treat this skin disease.

Acne Vulgaris↗