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Biomedical subjects

H Tagami

Publications and source records attributed to H Tagami.

At least 181 records · Page 10Linked to original sources

Sialyl LewisX expression on human Langerhans cells.

Recently, it has been demonstrated that the skin-infiltrating T cells express cutaneous lymphocyte-associated antigen, which is the ligand of E-selectin or endothelial-leukocyte adhesion molecule, suggesting that cutaneous lymphocyte-associated antigen functions as the homing receptor of the skin infiltrating T cells. In contrast, the mechanism for the migration of Langerhans cells from the bone marrow to the skin has not been clarified. Sialyl LewisX acts as a ligand for endothelial-leukocyte adhesion molecule and granule membrane protein 140. We examined the expression of sialyl LewisX in epidermal dendritic cells in human skin. Two-color immunofluorescence study on an epidermal sheet revealed that human leukocyte antigen DR+ or CD1a+ epidermal dendritic cells were partially sialyl LewisX+, although all of the sialyl LewisX+ dendritic cells were human leukocyte antigen DR+ and CD1a+. Further analysis of these dendritic cells by flow cytometry demonstrated that most of the human leukocyte antigen DR+ and CD1a+ epidermal cells expressed sialyl LewisX, although the magnitude of its expression was more variable than that of CD1a expression, and that some of human leukocyte antigen DR+ cells were clearly sialyl LewisX-. Immunoperoxidase study of normal skin showed the presence of sialyl LewisX+ dendritic cells not only in the epidermis but also in the upper dermis. These data demonstrating the heterogeneity of the expression of sialyl LewisX by epidermal Langerhans cells suggest their possible relationship to the stage of maturation as well as to the migration of Langerhans cells from the bone marrow to the skin.

Flow Cytometry↗

Up-regulation of alpha 4 integrin on activated Langerhans cells: analysis of adhesion molecules on Langerhans cells relating to their migration from skin to draining lymph nodes.

After hapten application, epidermal Langerhans cells migrate into the regional lymph nodes through dermal lymphatics. Recently, we have demonstrated that some of them take the phenotypic and functional characteristics similar to those of in vitro cultured Langerhans cells, before disappearing from the epidermis. To analyze the mechanisms underlying the migration of Langerhans cells, we studied the expression of several adhesion molecules on freshly isolated LC and cultured LC. Pgp-1 (CD44), intercellular adhesion molecule 1, and alpha 4 integrin were strongly expressed on cultured Langerhans cells. Among them, only alpha 4 integrin was strongly up-regulated by cultured Langerhans cells, because its expression by freshly isolated Langerhans cells was very weak. This up-regulation of alpha 4 integrin was also observed on in vivo activated Langerhans cells in the epidermis and draining lymph nodes after hapten application. These data suggest a possible role played by VLA-4 in the migration of Langerhans cells from the epidermis into the regional lymph nodes after hapten application.

Animals↗

Improvement in survival rate of patients with acral melanoma observed in the past 22 years in Sendai, Japan.

While the incidence of malignant melanoma is much lower in Japanese than in Caucasians, the commonest site of melanoma in Japanese has been reported to be the acral regions of the limbs. The survival rate for acral and nodular melanoma observed at the Department of Dermatology, Tohoku University Hospital in Sendai, Japan from 1969 to 1990 was reviewed. Among 150 melanoma patients 125 (83%) and 17 (11%) had primary cutaneous melanoma and mucous membrane melanomas, respectively. Frequent sites for cutaneous melanomas were the sole (31%) and subungual regions (15%). Comparison of the stages of plantar melanoma at diagnosis showed that the proportion of stages III and IV decreased after 1980 with a corresponding increase in those with a tumour thickness of less than 4 mm (stage II). Concurrently, the prognosis of plantar melanoma has improved; the 5-year survival rate in each of the three periods 1969-75, 1976-80 and 1981-85 was 21, 70 and 90%, respectively. This was also the case with subungual melanoma. Such improvements in the prognosis are thought to be mainly due to early detection through the growing public awareness of this life-threatening disease. By contrast cases of nodular melanoma increased sharply after 1980. Among these, the high proportion of patients in advanced stages (stages III and IV) remained static even after 1980, with a resultant low 5-year survival rate in the above mentioned periods of 33, 38 and 18%, respectively.

Female↗

Histoanalytical study of the cellular infiltrate in the tuberculin reaction.

In contrast to the generally held view, in previous studies it has been found that the histopathological changes in delayed-type hypersensitivity reactions to intradermal purified protein derivative of tuberculin (PPD) in humans were not uniform. These were classified into three types based on their resemblance to features seen in other dermatoses, i.e.: (i) perivascular dermatitis type; (ii) basal spongiotic dermatitis type; and (iii) erythema multiforme type. These histopathological patterns correlated well with the clinical response seen in tuberculin hypersensitivity of tested subjects. In the present study, the immunohistopathological features in 44 skin biopsy specimens were assessed quantitatively by using multivariate analysis. The numbers of infiltrating cells in the epidermis and in the dermis which were immunohistologically positive to monoclonal antibodies against various mononuclear cells were counted separately to determine if there was any statistical correlation between the histopathological patterns and the phenotypes of infiltrating cells. As a result, a significant correlation was found between the histopathological patterns and the phenotypes of cells infiltrating the epidermis, such as CD8+ cells, CD4+ cells, CD11c+ cells and interleukin 2 receptor positive cells. All these cells showed a high correlation coefficient to the expression of HLA-DR antigen by keratinocytes. Next, factors that might regulate the inflammation and interaction among the infiltrating cells were assessed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Enhancing effect of protein A on the interaction between opsonized corneocytes and neutrophils in staphylococcal infection.

Formation of subcorneal pustules characterizes skin lesions infected by Staphylococcus aureus. To elucidate the mechanism underlying the subcorneal pustule formation as well as that of anti-bacterial host defence, we studied the effect of staphylococcal protein A on the interaction between the stratum corneum (SC) and neutrophils. We found that protein A significantly promoted opsonized SC-induced chemiluminescence (CL) in neutrophils. This was specific to SC because no enhancement was observed with opsonized zymosan. It took place even with the serum obtained from a patient with agammaglobulinemia, ruling out the possibility of the involvement of Fc-receptors of neutrophils in this phenomenon. Microscopic observation of such SC revealed an increase in the number of neutrophils adhering to the surface of the protein A-coated corneocytes. Ultrastructural observation showed a distinct deformation of the neutrophils adhering to the surface of the corneocytes, suggesting that they are in an activated state. Such an enhanced interaction between protein A-attached SC and neutrophils seems to play an important role in the host defence mechanism against the invading S. aureus and in the production of the characteristic pustules by the neutrophil-mediated damage of the surrounding epidermal tissue.

Cell Communication↗

Mode of release of interleukin-8 from proliferating human epidermal keratinocytes in vitro.

Keratinocytes have been shown to express interleukin-8 (IL-8) mRNA on stimulation with IL-1 and other substances. This has been assumed to account for the large amount of this neutrophil chemotactic cytokine in psoriasis. We found that, without any added agents, commercially available normal human epidermal keratinocytes proliferating in Keratinocyte Growth Medium (KGM) released a chemotactic peptide extracellularly, which was confirmed to be IL-8. To determine whether most of the IL-8 is secreted extracellularly from proliferating keratinocytes or is mainly stored to be released only on stimulation. We quantified cell-associated and released immunoreactive IL-8 from keratinocytes cultured in KGM for up to 11 days at the peptide level. The keratinocytes proliferated, taking a sigmoid growth curve, to reach a plateau at day 7. We found that the amounts of immunoreactive IL-8 gradually increased in the culture supernatant with cell growth but its prominent release took place only after the cell growth reached a plateau. The cell-associated IL-8 was much smaller in amount than that noted in the supernatant. These results suggest that IL-8 constitutively produced by keratinocytes was mostly released extracellular but that the production by actively proliferating cells seems to be far less than that by non-proliferating cells that probably occurred in an autocrine fashion under the stimulation of keratinocyte-derived cytokines accumulated in the culture medium. Neutrophil chemotactic activity assayed concomitantly showed a consistent increase during the culture period, indicating that, with their growth, the keratinocytes release substances other than IL-8 that exert an influence on neutrophil chemotactic functions.

Cell Division↗

Influence of staphylococcal lipoteichoic acid on the frustrated phagocytosis of neutrophils against opsonized corneocytes.

Stratum corneum (SC) exerts a proinflammatory effect in the presence of complement. When Staphylococcus aureus (S. aureus) invades the skin through damaged SC, neutrophils accumulate at the subcorneal portion of epidermis to phagocytize the S. aureus as noted in impetigo. Besides the phagocytosis of bacteria, neutrophils interact with opsonized SC in a form of frustrated phagocytosis, increasing a damage of the surrounding tissues. Based on our previous finding that staphylococcal protein A promotes the interaction between SC and neutrophils, we investigated whether lipoteichoic acid (LTA), another cell wall component of S. aureus, also shows similar properties. We found that LTA significantly promoted the binding of neutrophils to opsonized SC, resulting in an increase in SC-induced respiratory burst of neutrophils assessed by chemiluminescence (CL). The binding of neutrophils to the SC was almost completely inhibited by the blocking of CR3 with anti-CD11b antibody, suggesting that the binding between SC and neutrophils is mediated by interaction between C3bi and CR3 (Mac-1). Such enhanced interaction seems to function in the primary host defence mechanism against the invading S. aureus through the skin such as in impetigo.

Antibodies, Monoclonal↗

The effect of topical tretinoin on the photodamaged skin of the Japanese.

Fifteen middle aged or elderly patients with chronic solar damage of the skin, eight patients with melasma and three patients with xeroderma pigmentosum were treated with topical tretinoin for 6 months. There was a significant improvement in fine surface lines in periorbital region, but no significant improvement was observed in deep furrows. No significant change was induced in melasma despite the improvement in smoothness of the skin surface. Global improvement was also seen in one patient with xeroderma pigmentosum. With regard to the functions of the stratum corneum that was assessed on the flexor surface of the forearms, values of water content as well as transepidermal water loss were found to increase one month after start of the application of tretinoin cream. On the other hand, there was no significant change in the amino acid content of the stratum corneum when measured after 4 months of the treatment. It is concluded that tretinoin cream is capable of partly reversing fine surface lines in photodamaged facial skin of the Japanese. However the irritation induced by 0.1% tretinoin cream was unexpectedly severe in the Japanese as compared to that reported in Caucasians.

Administration, Topical↗

Amelanotic acral melanoma masquerading as fibrous histiocytic tumours. Three case reports.

We report 3 cases of amelanotic melanoma developing on the finger, whose histology disclosed dermal invasion of histiocyte-like tumour cells. One of the 3 cases was subungual melanoma and the other 2 were on the volar surface of the finger tip. Because of the characteristic dense infiltration of large histiocyte-like tumour cells, including many multinucleated giant cells, we initially considered histiocytic tumours. However, there were some histiocyte-like cells that displayed inclusion-like intranuclear invagination of cytoplasm, and almost all tumour cells, including the giant cells, were positive for S-100 protein. In addition, ultrastructural demonstration of premelanosomes within the cytoplasm of the tumour cells established the diagnosis of amelanotic melanoma. These features were distinct histologically from other variants of vertical growth phase amelanotic malignant melanoma, including desmoplastic or neurotropic melanoma. Because we encountered cases 2 and 3 within just a year after the first case, we think that the misdiagnosis of amelanotic "histiocytic" melanoma can be avoided through enhanced clinical awareness and subsequent appropriate histopathologic studies.

Aged↗

Electrical measurement of the water content of the stratum corneum in vivo and in vitro under various conditions: comparison between skin surface hygrometer and corneometer in evaluation of the skin surface hydration state.

Two commercially available electrical instruments which evaluate the hydration state of the skin surface were compared in in vitro and in vivo experiments. The skin surface hygrometer (Skicon-200) employs high-frequency conductance, whereas the corneometer (CM 420, CM 820) uses electrical capacitance to determine the level of hydration. In a simulation model of in vivo stratum corneum (SC), the high frequency conductance device showed a much closer correlation with the hydration state of the surface SC (r = 0.99) than the capacitance device (r = 0.79), suggesting that the former can accurately assess the hydration dynamics of SC, particularly that due to the accumulation of easily releasable secondary bound water and free water. Both devices were insensitive to changes of hydration taking place in deeper viable skin tissues, e.g. the accumulated tissue fluids in suction blisters. Although the capacitance device correlated poorly with the hydration dynamics in normal SC, its sensitivity to changes occurring in extremely dry skin, such as scaly psoriatic lesions, suggests its measurements characteristics at an extremely low state of hydration, consisting of mostly bound water, such as noted in pathologic SC.

Adolescent↗

Epidermodysplasia verruciformis accompanied by familial large granular lymphocytosis and a decrease in T lymphocytes.

A 40-year-old man with epidermodysplasia verruciformis showed a decrease in peripheral blood T cells and abnormal expansion of large granular lymphocytes, accompanied by increased natural killer cell activity. Surface marker analysis of his large granular lymphocytes demonstrated that the subset, CD 57+ and CD 16+, had increased. His father, who had no skin lesions of epidermodysplasia verruciformis, displayed similar blood changes and his brother showed a decrease in T cells and a slight increase in CD 16+ natural killer cells, whereas his mother revealed only a slight decrease in T cells. Our present study indicates that epidermodysplasia verruciformis might be associated with hereditary abnormal expansion of large granular lymphocytes and a decrease in T cells.

Adult↗

Quantification of chemotactic peptides (C5a anaphylatoxin and IL-8) in psoriatic lesional skin.

BACKGROUND AND DESIGN: Psoriatic scale extracts contain a unique chemotactic peptide fraction that is likely to be involved in the induction of rhythmic transepidermal leukocyte chemotaxis. Recent studies have identified the presence of two unrelated chemotactic peptides in this fraction, ie, C5a/C5a des Arg and interleukin 8 (IL-8), and its related cytokines. To investigate their relative contribution to the transepidermal leukocyte migration as well as their interrelationship in psoriatic lesions, we have quantified concentrations of immunoreactive C5a/C5a des Arg and IL-8 in psoriatic lesional scale extracts and those from related sterile pustular dermatoses such as subcorneal pustular dermatosis and pustulosis palmaris et plantaris. RESULTS: The concentrations of C5a/C5a des Arg and IL-8 were more significantly increased in the horny-tissue extracts from lesional skin than in those from noninflammatory orthokeratotic skin (P < .01). The increase of C5a/C5a des Arg concentration was specific to the lesional scale extracts, but showed a rather wide range of variation. By contrast, IL-8 concentration, although consistently increased in the lesional scale extracts, was also moderately increased even in noninflammatory scale extracts prepared from ichthyosis vulgaris. The elevation of IL-8 levels in psoriatic lesions was also confirmed by measuring their levels in cutaneous tissue fluid samples collected from suction blisters. However, unexpectedly, some control samples obtained from normal skin also showed a moderate increase in the IL-8 level. Neutrophil chemotactic activity correlated significantly only with the levels of C5a/C5a des Arg in the scales (P < .05). No such significant correlation was found between chemotactic activity and IL-8 or between C5a/C5a des Arg and IL-8. CONCLUSION: Based on these results, we speculate that, although IL-8 may exert a synergistic effect with C5a/C5a des Arg in the induction of transepidermal leukocyte chemotaxis, it constitutes a proinflammatory cytokine that is involved in the production of the persistent inflammatory changes characterized by a T-lymphocyte infiltration. In contrast, C5a/C5a des Arg seems to be generated only in the inflammatory lesional skin under specific circumstances that preferentially favor complement activation and also seems to play a major role in the induction of cyclic transepidermal leukocyte chemotaxis from "squirting papillae."

Adolescent↗

Identification of a cis-acting element that enhances the pigment cell-specific expression of the human tyrosinase gene.

To identify the cis-acting element that is responsible for the pigment cell-specific expression of the human tyrosinase gene, we analyzed the promoter activity of its 5'-flanking region by transient expression assays. The fusion genes were constructed by inserting the 5'-flanking region of the human tyrosinase gene upstream from the firefly luciferase gene and were introduced into human melanoma cells and HeLa cells. We thus found the element, located between 2.7 and 1.8 kilobase pairs upstream from the transcription initiation site, that enhances the transient expression of the luciferase reporter gene in melanoma cells, but not in HeLa cells, the tyrosinase gene expression of which is not detectable. Using the fusion genes containing putative enhancer elements under the control of the heterologous simian virus 40 promoter, we identified the pigment cell-specific enhancer of approximately 200 base pairs (bp) between -2.0 and -1.8 kilobase pairs and localized the core sequence to a 39-bp region. This 39-bp core element was then confirmed to direct the melanoma cell-specific expression of the reporter gene under the tyrosinase gene promoter. We thus propose that this core element is responsible for the pigment cell-specific expression of the human tyrosinase gene.

Animals↗

Downstream region of the human tyrosinase-related protein gene enhances its promoter activity.

We have cloned and sequenced the human genomic DNA segments encoding the 5'-flanking region and the first two exons of the tyrosinase-related protein (TRP) gene, a pigment cell-specific gene. Functional analysis of its promoter suggests that the downstream region of the TRP gene, including the first intron, enhances the transient expression of the luciferase gene under control of the TRP gene promoter about 16- to 20-fold. This enhancer-like activity is detected not only in melanoma cells but also in HeLa cells whose TRP gene expression is assumed to be repressed. We suggest a possibility that the downstream region is not sufficient to confer pigment cell-specific expression, but is required for efficient transcription of the TRP gene in pigment cells.

Animals↗

The role of complement-derived mediators in inflammatory skin diseases.

The complement system represents an important nonspecific skin defense mechanism. Its activation leads to the generation of products that not only help to maintain normal host defenses but also mediate inflammation and tissue injury. Proinflammatory products of complement include large fragments of C3 with opsonic and cell-stimulatory activities (C3b and C3bi), low molecular weight anaphylatoxins (C3a, C4a, and C5a), and membrane attack complex. Among them C5a or its degradation product C5a des Arg seems to be the most important mediator because it exerts a potent chemotactic effect on inflammatory cells. Intradermal administration of C5a anaphylatoxin induces skin changes quite similar to those observed in cutaneous hypersensitivity vasculitis that occurs through immune complex-mediated complement activation. Complement activation is involved in the pathogenesis of the inflammatory changes in autoimmune bullous dermatoses. In pemphigus complement activation by pemphigus antibody in the epidermis seems to be responsible for the development of characteristic inflammatory changes termed eosinophilic spongiosis. In bullous pemphigoid (BP) interaction of basement membrane zone antigen and BP antibody leads to complement activation that seems to be related to leukocytes lining the dermoepidermal junction. Resultant anaphylatoxins not only activate the infiltrating leukocytes but also induce mast cell degranulation which facilitates dermoepidermal separation and eosinophil infiltration. Similar complement activation seems to play a more direct role in the dermoepidermal separation noted in epidermolysis bullosa acquisita and herpes gestationis. Anaphylatoxin generation via the alternative pathway activation under light irradiation is implicated in the development of the immediate erythematous phototoxic reactions induced by such well-known chemicals as porphyrin, chlorothiazide, demethylchlortetracycline, and chlorpromazine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acne Vulgaris↗

Cloning and sequence analysis of the tyrosinase gene from a patient with tyrosinase-positive oculocutaneous albinism.

Tyrosinase is synthesized on membrane-bound ribosomes and transported into melanosomes through smooth endoplasmic reticulum and Golgi apparatus. Melanin polymers are produced only in melanosomes but never in smooth endoplasmic reticulum or Golgi apparatus, indicating that posttranslational modifications of tyrosinase are completed with melanosomes where tyrosinase becomes an active form. Based on a working hypothesis that tyrosinase-positive oculocutaneous albinism is a consequence of the structurally altered tyrosinase due to a point mutation in the gene of its gene coding for a glycosylation site or a membrane-binding site, which leads to the impairment in the posttranslational modification of tyrosinase and its catalytic activity, we have cloned the tyrosinase gene of one patient affected with tyrosinase-positive oculocutaneous albinism and determined its nucleotide sequence. Thus demonstrated all exons' nucleotide sequence of the patient's tyrosinase gene was found to be identical to that of the wild-type gene. The results indicate that the patient's tyrosinase itself is not altered. We therefore propose that the molecular basis for the development of tyrosinase-positive oculocutaneous albinism exists as a defect in other proteins required for the activation of tyrosinase or in other regions of the tyrosinase gene.

Adult↗