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Biomedical subjects

M Morohashi

Publications and source records attributed to M Morohashi.

At least 55 records · Page 3Linked to original sources

Relationship between Propionibacterium acnes biotypes and Jumi-haidoku-to.

We examined the relationship between Propionibacterium acnes biotypes and Jumi-haidoku-to (JHT). In all the P. acnes strains tested, the production of propionic acid (PA) and butyric acid (BA) was suppressed in a medium containing 1 mg/ml JHT compared with the control medium without JHT. There were no significant differences in the rates of decreased PA and BA production between P. acnes biotype 3 (B3) and the other biotypes or between isolates from mild skin rash and more severe skin rash. P. acnes B3 was the most commonly identified biotype. The clinical effects on acne due to the anti-P. acnes lipase activity of JHT did not seem to be influenced by the degree of acne rash or the P. acnes biotype.

Acne Vulgaris↗

Proboscis amputation facilitates the study of mosquito (Diptera: Culicidae) attractants, repellents, and host preference.

Proboscis amputation has facilitated the study of mosquito behavior. Using humans as a host is very important in the study of mosquito attractants, repellents, and host preference. However, mosquito bites cause potential medical problems because of hypersensitivity and perhaps secondary bacterial infection, even using laboratory mosquitoes. Moreover, once a normal female mosquito bites and feeds on human blood, it cannot be used in subsequent probing tests. These problems were resolved by proboscis amputation. Variation of attraction among humans was examined effectively without bites using proboscis-amputated Aedes albopictus Skuse. Proboscis-amputated and normal mosquitoes also showed equal repellency against 1% L-lactic acid. Although the mosquitoes lacked the tip of the labium and some sensilla, they alighted on human forearms in the same way as normal mosquitoes. Because proboscis-amputated mosquitoes continued to probe avidly, they could be used repeatedly, thereby reducing the number of mosquitoes required for experimentation. The use of proboscis-amputated mosquitoes would promote various studies of mosquito attraction or repellency with no risk of hypersensitivity and secondary bacterial infection by mosquito bites.

Aedes↗

Differential expression of the chemokine receptors by the Th1- and Th2-type effector populations within circulating CD4+ T cells.

The in vitro studies have proposed that human Th1 cells favor expression of CXCR3 or CCR5, whereas Th2 cells favor CCR3 and CCR4. In this study, the in vivo relevance of expression of these chemokine receptors on Th cells was investigated in patients with atopic dermatitis (AD) as the Th2-dominated disorder and nonatopic normal individuals. Flow-cytometric analysis using monoclonal antibodies against CXCR3, CCR5, CCR3, and CCR4 disclosed that a substantial proportion of memory (CD45RO+) CD4+ T cells in the blood of AD and normal patients expressed CXCR3, CCR5, or CCR4, but expression of CCR3 on these cells was negligible. Stimulation studies combined with intracellular cytokine staining revealed that the cells capable of producing Th2 cytokines, such as interleukin-4 (IL-4), IL-5, and IL-13, were restricted to the CCR4-expressing population within memory CD4+ T cells. Concerning Th1 cytokine production, interferon-gamma (IFN-gamma)-producing cells resided exclusively in CXCR3-expressing memory CD4+ T cells, although IFN-gamma production was found in both memory CD4+ T cells with and without CCR5 expression. We observed that CCR4-expressing memory CD4+ T cells in the blood were more increased in AD patients as compared with normal patients, whereas CXCR3-expressing memory CD4+ T cells were present in a lower frequency in AD than seen in normal patients. These results suggest that CXCR3 and CCR4, but not CCR5 or CCR3, appear to serve as the useful markers for identification of circulating Th1 and Th2 effector populations.

Adult↗

A gene network inference method from continuous-value gene expression data of wild-type and mutants.

In this paper we introduce a new inference method of a gene regulatory network from steady-state gene expression data. Our method determines a regulatory structure consistent with an observed set of steady-state expression profiles, each generated from wild-type and single deletion mutant of the target network. Our method derives the regulatory relationships in the network using a graph theoretic approach. The advantage of our method is to be able to deal with continuous values of steady-state data, while most of the methods proposed in past use a Boolean network model with binary data. Performance of our method is evaluated on simulated networks with varying the size of networks, indegree of each gene, and the data characteristics (continuous-value/binary), and is compared with that of predictor method proposed by Ideker et al. As a result, we show the superiority of using continuous values to binary values, and the performance of our method is much better than that of the predictor method.

Animals↗

Emergence of resistance to acyclovir and penciclovir in varicella-zoster virus and genetic analysis of acyclovir-resistant variants.

We have characterized the differential actions of acyclovir and penciclovir against varicella-zoster virus (VZV) in cell culture by comparing the frequency of appearance of resistant viruses followed by their characterization. Cells were infected with cell-free virus and the cultures were successively treated with increasing concentrations of acyclovir or penciclovir. Drug-resistant viruses were selected in the presence of 6 microg/ml of acyclovir or penciclovir. The emergence frequency of resistant viruses was significantly higher following acyclovir exposure than following penciclovir exposure (Fisher's exact test, P<0.0001), possibly reflecting virus growth differences under these experimental conditions. Based on antiviral drug susceptibility and thymidine kinase (TK) activity assays, 11 acyclovir-resistant variants from seven experiments using three virus strains (Kawaguchi strain, Oka varicella vaccine strain and a clinical isolate from a zoster patient) were found to be TK-deficient. Sequence analysis of TK-deficient variants of the Kawaguchi strain revealed deletions that caused frameshifts, resulting in premature termination in the TK gene.

Acyclovir↗

Calcitonin gene-related peptide upregulates melanogenesis and enhances melanocyte dendricity via induction of keratinocyte-derived melanotrophic factors.

It has recently been shown that cutaneous axon terminals and epidermal melanocytes make contact via chemical synapses in human skin and that calcitonin gene-related peptide (CGRP) induces melanocyte proliferation. To further clarify the effect of neuropeptides on the biology and morphology of melanocytes, especially with respect to melanogenesis and melanocyte dendricity, organ cultures of normal human skin and cultured melanocytes were exposed to various neuropeptides present in intraepidermal nerve endings. Of the neuropeptides examined, skin exposed to CGRP in organ culture showed increases in melanocyte number, epidermal melanin content, melanosome number, and degree of melanization. CGRP alone had no significant effect on melanogenesis of cultured melanocytes, whereas the addition of medium conditioned by CGRP-stimulated keratinocytes (CGRP-KCM) induced melanogenesis as indicated by biochemical assays of tyrosinase activity and melanin content. Furthermore, CGRP-KCM significantly enhanced melanocyte dendricity, a crucial factor affecting epidermal pigmentation. These findings suggest that keratinocytes produce and secrete some melanotrophic factors following stimulation with CGRP, which modulate growth, melanin synthesis, and dendricity of melanocytes. These data demonstrate intimate interactions between the cutaneous nervous system and melanocytes within the epidermal environment.

Calcitonin Gene-Related Peptide↗

The induction by topical minoxidil of increased fenestration in the perifollicular capillary wall.

We report the induction by topical minoxidil of increased fenestration in the perifollicular capillary wall. Male 30-day-old Wistar rats were divided into two groups, i.e. an experimental group which received 4% minoxidil solution topically on the dorsal skin, and a control group which received only vehicle solution topically. Using transmission electron microscopy, follicular and subepidermal capillaries and dermal fibres were compared between both groups. There were no obvious differences in subepidermal capillaries or dermal fibres between the two groups. However, topically applied minoxidil increased fenestration in follicular capillary walls around anagen hair bulbs.

Administration, Topical↗

Comparative study of staphylococci from the skin of atopic dermatitis patients and from healthy subjects.

BACKGROUND: Bacterial infections occur frequently on the skin of atopic dermatitis (AD) patients. The objectives of this study were to evaluate the microbiology of the skin of AD patients for staphylococci, the frequency and density of each species, and their susceptibility to antimicrobial drugs. METHODS: To study the staphylococci present on the skin of 21 AD outpatients and of 12 healthy subjects (HS), cutaneous organisms were obtained using the contact-plate method. RESULTS: Staphylococcus aureus was isolated in 85.7% of AD patients (mild type, 77.8%; moderate type, 87.8%; and severe type, 100%) and in 25% of HS, while Staphylococcus epidermidis was isolated in 83.3% of HS and in 38.1% of AD patients. Among the coagulase-negative staphylococci (CNS) identified, S. epidermidis was the common type and several other CNS were detected in both AD patients and HS. As the eruption grade of dermatitic skin became more severe, the average density of S. aureus increased (severe, 2.68 +/- 0.86; moderate, 2.49 +/- 0.48; mild, 2.28 +/- 0.44). A reversed tendency was seen in S. epidermidis (severe, 1.80; moderate, 1.90; mild, 2.10). Among nine antimicrobial drugs tested against S. aureus, S. epidermidis, and some other types of CNS isolates, vancomycin (VCM) and minocycline (MINO) were the most active, gentamycin (GM) was the less active, and ampicillin (ABPC) was the least active. CONCLUSIONS: The skin of AD patients was more frequently colonized with S. aureus than that of normal controls. As the severity of the AD lesions increased, the numbers of S. aureus isolated increased. The skin of HS was more colonized with S. epidermidis. Other species of CNS were isolated from several cases of AD patients and HS. In addition, S. aureus, S. epidermidis, and the other CNS showed poor susceptibility to some of the tested antimicrobial drugs.

Adolescent↗

Characteristics of Streptococcus species isolated from infectious skin diseases.

During the period from January of 1995 to June of 1998, 27 beta-hemolytic streptococci were isolated from 25 cases of infectious skin diseases including secondary infections, impetigo, phlegmone, and paronychia. The rate of beta-hemolytic streptococci among all kinds of the isolates was found to be similar during those 4 years, ranging from 3.5% to 5.6%. Staphylococcus aureus were found to coexist with beta-hemolytic streptococci in 20 (80%) out of 25 cases. beta-hemolytic streptococci were also often associated with coagulase-negative staphylococci, gram-positive rods, or other species. Twelve cases (48%) carried beta-hemolytic streptococci predominantly. Most beta-hemolytic streptococci showed high susceptibilities to all antimicrobials tested; however S. agalactiae showed no susceptibility to gentamicin. The evaluation of characteristics of Streptococcus species is very important for selecting the right antimicrobial agents and the proper term of chemotherapy.

Adolescent↗

Phytol is a novel tumor promoter on ICR mouse skin.

Phytol is a branched, long-chain aliphatic alcohol which has various biological effects. In this study, we examined phytol as a tumor promoter in a mouse skin initiation-promotion model, and compared its promotion activity with that of 12-O-tetradecanoyl phorbol-13-acetate (TPA). Female ICR mice, 7 weeks of age, were initiated with 100 microg of 7,12-dimethylbenz(a)anthracene, and were then topically promoted twice a week for 16 weeks with 100 mg of phytol or with 2.5 microg of TPA. In this model 95% of animals treated with phytol developed skin tumors within 16 weeks. The average number of lesions per mouse treated with phytol was significantly lower than that in mice treated with TPA, and this significant difference continued up to 16 weeks after the end of promotion treatment. Characterization of hyperplasia 48 h after topical application of agents showed that epidermal thickness and vertical thickness following topical application of phytol were significantly increased compared with vehicle controls, but were significantly smaller than in animals treated with TPA. Ornithine decarboxylase (ODC) activity following topical application of phytol was increased in a dose-dependent manner and showed a weak, delayed induction (which was maximal 11-12 h after treatment) as compared with the case of TPA. The specific binding of [3H]phorbol-12,13-dibutyrate (PDBU) by JB6 cells was not inhibited by phytol at concentrations up to 1 mM. These results indicate that phytol has a weak tumor promoter activity compared to TPA and is a non-TPA-type tumor promoter in this model of mouse skin carcinogenesis.

Animals↗

Extent of laminin-5 assembly and secretion effect junctional epidermolysis bullosa phenotype.

Junctional epidermolysis bullosa (JEB) is an autosomal recessive skin blistering disease with both lethal and nonlethal forms, with most patients shown to have defects in laminin-5. We analyzed the location of mutations, gene expression levels, and protein chain assembly of the laminin-5 heterotrimer in six JEB patients to determine how the type of genetic lesion influences the pathophysiology of JEB. Mutations within laminin-5 genes were diversely located, with the most severe forms of JEB correlating best with premature termination codons, rather than mapping to any particular protein domain. In all six JEB patients, the laminin-5 assembly intermediates we observed were as predicted by our previous work indicating that the alpha3beta3gamma2 heterotrimer assembles intracellularly via a beta3gamma2 heterodimer intermediate. Since assembly precedes secretion, mutations that disrupt protein-protein interactions needed for assembly are predicted to limit the secretion of laminin-5, and likely to interfere with function. However, our data indicate that typically the most severe mutations diminish mRNA stability, and serve as functional null alleles that block chain assembly by resulting in either a deficiency (in the nonlethal mitis variety) or a complete absence (in lethal Herlitz-JEB) of one of the chains needed for laminin-5 heterotrimer assembly.

Adult↗

Suppression of recurrent genital herpes simplex virus type 2 infection by Rhus javanica in guinea pigs.

Rhus javanica has been shown to exhibit anti-herpes simplex virus (HSV) activity and potentiate the anti-HSV activity of acyclovir in vitro and in vivo. This extract was examined for its suppressive efficacy on recurrent genital infection in guinea pigs. Guinea pigs were primarily infected intravaginally with HSV type 2 (HSV-2). Prophylactic oral administration, at the dose corresponding to human use, of R. javanica significantly reduced the incidence, severity and/or frequency of spontaneous and severe skin lesions as compared with latently infected guinea pigs administered with water. This prophylactic efficacy was confirmed by the crossover administration, for more than 2 months, of R. javanica and water to the infected guinea pigs. Toxicity, such as weight loss, from R. javanica administration was not observed in the guinea pigs. When recurrent HSV-2 disease was induced by ultraviolet irradiation 3 months after primary infection, the prophylaxis with R. javanica was also significantly effective in reducing the severity of ultraviolet-induced skin lesions. Thus, prophylaxis of recurrent genital HSV-2 infection with R. javanica may preserve the efficacy of acyclovir by reducing both the use of acyclovir and the appearance of acyclovir-resistant viruses.

Administration, Intravaginal↗

Morphological alterations of epidermal melanocytes in photoageing: an ultrastructural and cytomorphometric study.

To examine pathological changes of melanocytes in photodamaged skin, we performed a comparative cytomorphometric analysis and a qualitative observation of melanocytes from sun-exposed and sun-protected facial skin at the electron microscopic level. The characteristic ultrastructural features of melanocytes in photodamaged skin included a statistically significant increase in their number, a marked nuclear heterogeneity, signs of cell activation, close apposition to photodamaged degenerate keratinocytes, degenerative changes represented by large intracytoplasmic vacuoles, and frequent direct contacts with Langerhans cells. Cytomorphometric analysis revealed significant decreases in cell and nuclear sizes, increases in cell and nuclear perimeters accompanied by irregular contours, and higher degrees of nuclear ellipticity in sun-exposed melanocytes. This study demonstrates that there are remarkable differences in the morphology of melanocytes between photoaged and intrinsically aged facial skin, and supports the concept that photoageing processes contribute to cytological alterations in melanocytes.

Aged↗

Morphological assessment of the effects of cyclosporin A on mast cell--nerve relationship in atopic dermatitis.

There is considerable clinical and experimental evidence that cyclosporin A has powerful therapeutic effects on severe, therapy-resistant atopic dermatitis. To further clarify the mechanism of beneficial action of cyclosporin A for atopic dermatitis, we assessed its effects on mast cell morphology and on the topographical relationship between mast cells and cutaneous nerves in lesional skin of atopic dermatitis. The ultrastructural features of mast cell-specific granules in cyclosporin A-treated skin compared with those in the pretreated skin included an increase in the stable granule population and the disappearance of signs of granule exocytosis. The close apposition of mast cells to peripheral nerve fibres in the upper dermis and an invasion of mast cells into nerve bundles in the lower dermis were immunohistochemically noted, and an intimate association between mast cells and unmyelinated dermal nerves or Schwann cells was observed ultrastructurally in the pretreated lesional skin. After cyclosporin A therapy, the close interrelation of mast cells and cutaneous nerves was not seen. These findings suggest that cyclosporin A may exert its therapeutic efficacy by inhibiting mast cell activation, and by affecting the interaction between mast cells and nerves, which may explain the beneficial therapeutic action of cyclosporin A in the management of the disease.

Adult↗

Benign sebaceous neoplasm with prominent epidermal component.

A 65-year-old woman presented with a solitary nodule within an erythematous plaque in her right groin. Histopathologic examination showed central lobular proliferation of basaloid cells admixed with mature sebaceous cells and a lateral extensive intraepidermal component composed mostly of lobules of mature sebocytes consistent with intraepidermal epithelioma with sebaceous differentiation and focal invasion. Although various cutaneous neoplasms may show an intraepidermal growth pattern, extensive sebaceous differentiation in such a neoplasm, as seen in this case, has not been described. Electron-microscopic study revealed that the basaloid cells have features of pluripotential cells. This observation supports the previously reported concept that intraepidermal epithelioma may be composed of a group of heterogeneous tumors with various degrees and lines of differentiation. Additionally, sebaceous epithelioma/adenoma should be considered in the differential diagnosis of the cutaneous neoplasms with an intraepidermal growth pattern.

Aged↗

Solitary basaloid follicular hamartoma.

We present a case of solitary basaloid follicular hamartoma of 8 years' duration on the nose of a 55-year-old Japanese man. Clinical examination revealed a solitary, asymptomatic, smooth-surfaced, black papule. Histologically, the lesion showed multifocal proliferation of basaloid cells forming islands, branching cords and anastomosing strands that were continuous with the basal layer of the epidermis. Individual hair follicles were replaced by these undifferentiated basaloid proliferating cells. Some abortive hair follicle-like structures composed of follicular bulbs and contiguous rudimentary dermal papillae were observed. This solitary papular type of basaloid follicular hamartoma is quite rare; our case is clearly distinguished from other neoplasms with hair follicle differentiation as well as from infundibulocystic basal cell carcinoma, which have been the most problematic differential diagnoses in the recent dermatopathologic literature.

Basal Cell Carcinoma↗

An overview of topical antibiotics for acne treatment.

Topical use of antibiotics is currently a widely accepted effective and safe treatment for acne. A review of the articles published in the past 30 years revealed that topical application of antibiotics such as erythromycin, clindamycin or tetracycline showed clinical effectiveness for mild to moderate inflammatory acne, especially when they are combined with zinc, tretinoin or benzoyl peroxide, while they showed little influence on noninflammatory acne. The main mechanism of action of topical antibiotics for acne treatment is inhibition of inflammation caused by bacteria rather than a direct bactericidal effect. The adverse reactions of topical antibiotics are mostly minor and negligible, while special attention should be given to the risk of development of resistant strains of Propionibacterium acnes. The development of new antibiotics is promising and will provide a wider range of therapeutic options for refractory cases.

Acne Vulgaris↗