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Biomedical subjects

Hachiro Tagami

Publications and source records attributed to Hachiro Tagami.

At least 37 records · Page 2Linked to original sources

Indolent herpetic whitlow of the toe in an elderly patient with diabetic neuropathy.

We report a case of indolent herpetic whitlow of the toe occurring in an elderly male patient with poorly controlled diabetes mellitus. In this case, the mechanism of transmission was not clear, although he was in a habit of taking a hot spring bath. This patient's symptoms were unusual for herpes simplex; he had no pain in the presence of diabetic neuropathy. The standard therapeutic dose of acyclovir was not effective in suppressing the lesions, and a higher dose was required to induce complete healing.

Acyclovir↗

Generation of leukemia-specific T-helper type 1 cells applicable to human leukemia cell-therapy.

Leukemic dendritic cells (DC) were induced from the peripheral blood (PB) or bone marrow (BM) of leukemia patients by culture with (i) GM-CSF + IL-3 (neutral condition); (ii) GM-CSF + IL-3 + IL-12 + IFN-gamma (type 1-condition); or (iii) GM-CSF + IL-3 + IL-4 (type 2-condition). Although leukemic cells rapidly differentiated into adhesive leukemic DC in all culture conditions, type1-conditions were the most suitable for inducing leukemic DC expressing high levels of HLA and costimulatory molecules. Addition of IL-2 after 2 days of culture induced a preferential growth of minor T cell populations interacting with leukemic DC. In particular, IFN-gamma-producing CD4+ Th1 cells were efficiently expanded in type 1 culture conditions but nor in neutral or type 2-conditions. However, CD4+ T cells expanded in neutral conditions showed Th1-like functions if they were pulsed with IFN-gamma for 2 days before harvest. Such Th1 cells produced IFN-gamma and exhibited cytotoxicity in response to autologous leukemia cells. We further demonstrated that IFN-gamma production of leukemia-specific Th1 cells was blocked by anti-HLA-DR mAb. Thus, we established a novel culture system for inducing leukemia-specific Th1 cells.

Adult↗

Detection of various types of human papillomavirus DNA, mainly belonging to the cutaneous-group, more frequently in normal tissue than in squamous cell carcinomas of the lip.

BACKGROUND: Mucosal high-risk human papillomaviruses (HPVs), such as type 16, are detectable in oral cancers, especially of the oropharynx and tonsils, and there is evidence that they play a pathogenetic role in some cases. However, information is limited about their significance for cancers of the vermilion of the lip. OBJECTIVE: To determine the detection rate, types and localization of HPVs in squamous cell carcinomas (SCCs) of the lip. METHODS: Nested PCR for cutaneous HPVs, including epidermodysplasia verruciformis-related HPV (EV-HPV), and single PCR for mucosal HPVs, were conducted for a total of 27 SCCs and normal samples from 30 individuals. Tyramide-based in situ hybridization (ISH) was also applied. RESULTS: Various types of HPVs were detected, particularly from normal individuals. Among the kinds of the HPV types detected in this study, half were found by PCR using a primer pair, which we newly designed. The prevalence of HPV was 5 out of 27 SCCs (ca. 18%) and 10 out of 30 normal individuals (ca. 33%). They were the entire cutaneous-group except for two, from one SCC and one normal individual. CONCLUSION: On the surface of the normal lip various types of mainly cutaneous-group HPVs may be present, but there does not appear to be any obvious association with SCCs developing in this site.

Aged↗

High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism.

Embryonic cells are expected to possess high growth/differentiation potential, required for organ morphogenesis and expansion during development. However, little is known about the intrinsic properties of embryonic epithelial cells due to difficulties in their isolation and cultivation. We report here that pure keratinocyte populations from E15.5 mouse embryos commit irreversibly to differentiation much earlier than newborn cells. Notch signaling, which promotes keratinocyte differentiation, is upregulated in embryonic keratinocyte and epidermis, and elevated caspase 3 expression, which we identify as a transcriptional Notch1 target, accounts in part for the high commitment of embryonic keratinocytes to terminal differentiation. In vivo, lack of caspase 3 results in increased proliferation and decreased differentiation of interfollicular embryonic keratinocytes, together with decreased activation of PKC-delta, a caspase 3 substrate which functions as a positive regulator of keratinocyte differentiation. Thus, a Notch1-caspase 3 regulatory mechanism underlies the intrinsically high commitment of embryonic keratinocytes to terminal differentiation.

Animals↗

BRAF point mutations in primary melanoma show different prevalences by subtype.

To elucidate the biological significance of activating mutations of BRAF in human malignant tumors, we performed a mutation analysis using 43 cell lines established from tumors that had developed in several kinds of human organs. Because the same V599E point mutation was observed in three of six melanoma cell lines and no such mutations were observed in other types of cancers, we focused further on melanoma, performed mutation analyses of NRAS, KRAS, CTNNB1, and p16/p14(ARF) in these cell lines, and found one NRAS mutation and three p16/p14(ARF) mutations. We further searched for mutations of BRAF and NRAS in 35 primary sporadic melanomas from 35 Japanese patients and detected the V599E BRAF point mutation in only nine (26%) of them. Significant differences in mutation frequency were observed among four histological subtypes; four (50%) of eight superficially spreading melanoma and five (33%) of 15 acral lentiginous melanoma had the mutation, whereas none of 12 other types (six nodular melanoma, five lentigo melanoma, and one mucosal melanoma) had it. The BRAF mutation was observed frequently even in small lesions, indicating that activation of this gene may be one of the early events in the pathogenesis of some melanomas.

Base Sequence↗

Peritumoral CpG oligodeoxynucleotide treatment inhibits tumor growth and metastasis of B16F10 melanoma cells.

Although melanoma mostly affects the skin, it is notorious for its propensity to easily develop metastasis. Metastatic melanoma is highly resistant to a variety of therapies. We examined the anti-metastatic potential of peritumoral monotherapy against murine cutaneous B16F10 melanoma with synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs. We demonstrated that repeated peritumoral injections of CpG ODN significantly reduced skin tumor size. Peritumoral CpG ODN-treatment of skin tumors prevented the development of pulmonary B16F10 colonies. Adoptive transfer of splenocytes obtained from CpG ODN-treated mice markedly reduced the number of previously established pulmonary colonies in recipient naïve mice. T-lymphocyte depletion studies indicated that the anti-metastatic effect was dependent on both CD4+ and CD8+ T cells. These results suggest that CpG ODN are promising as a preventive and therapeutic anti-metastatic measure against melanoma.

Adoptive Transfer↗

p38 Mitogen-Activated protein kinase mediates dual role of ultraviolet B radiation in induction of maturation and apoptosis of monocyte-derived dendritic cells.

Although ultraviolet B (UVB) induces apoptosis and functional perturbations in dendritic cells (DC), for example, Langerhans cells (LC), it also stimulates some LC into maturation after irradiation in vivo. To analyze its reciprocal effects on DC, we elucidated the direct effect of UVB on DC in vitro using human monocyte-derived DC (MoDC). UVB from 50 to 200 J per m2 stimulated the maturation of MoDC with (1) augmented expression of CD86 and HLA-DR, (2) enhanced production of IL-1beta, IL-6, IL-8, and TNF-alpha at both the mRNA and protein levels, and (3) enhanced allostimulatory capacity on a per-cell basis, whereas the exceeded doses induced apoptotic cell death. Western-blot analysis of MoDC after UVB demonstrated a concentration-dependent phosphorylation of p38- and c-JUN N-terminal kinase (JNK)-mitogen-activated protein kinases (MAPK), but not that of extracellular signal-regulated kinases. p38 MAPK-inhibitor, SB203580, inhibited both UVB-induced maturation and apoptosis of MoDC. Interestingly, MoDC that had undergone apoptosis exhibited an augmented expression of HLA-DR without upregulation of CD86 antigen, suggesting their tolerogenic phenotype. Thus, our study revealed a dual effect of UVB, to stimulate maturation or to induce apoptosis in MoDC, depending on the dosage, via p38 MAPK pathway.

Adult↗

Ber-EP4 antigen is a marker for a cell population related to the secondary hair germ.

Ber-EP4 is an antibody to a cell membrane glycoprotein of unknown function. In the skin, Ber-EP4 immunoreactivity has been reported to be localized in structures composed of basaloid epithelial cells, i.e. fetal epithelial germ cells, basal cell carcinoma, and trichoepithelioma as well as eccrine or apocrine ducts. In this study, we further characterized the follicular expression of Ber-EP4 immunoreactivity at different stages of the hair cycle of human terminal hair follicles. In addition, to clarify the location of Ber-EP4(+) cells, we compared the Ber-EP4 immunoreactivity with the expression of keratin 15 and keratin 19. Positive staining by Ber-EP4 was found in the lower part of the epithelial strand of late catagen hair follicles, in the secondary hair germ of telogen hair follicles, and in the matrix of early anagen hair follicles but not in any parts of mature anagen hair follicles. In contrast, the follicular expression of keratin 15 detected by using LHK15 antibody was restricted to two distinct parts of anagen hair follicles, i.e. the outer root sheath above the hair bulb and that of the isthmus including the bulge area, and to the outer root sheath of late catagen and telogen hair follicles. The follicular expressions of keratin 19 and that of keratin 15 were apparently superimposed, whereas keratin 15 expression was more extended. The immunoreactivity of LHK15 antibody and antikeratin 19 antibody against the secondary hair germ of telogen follicles was negative or dim. Our results suggest that Ber-EP4 reacts with the secondary hair germ and possibly a cell population related to the secondary hair germ but not with the presumptive stem cell population as revealed immunohistochemically either by the keratin 15 or keratin 19 expression.

Antibodies, Monoclonal↗

Delayed development of foreign body granuloma from an implanted permanent cardiac pacemaker.

We report a case of a late-developing cutaneous mass on the chest wall that proved to be non-specific mixed cell granuloma adjacent to the lead-electrode parts of a permanent cardiac-pacemaker that had been implanted in the left chest of an 81-year-old man 6 years previously. The lesion was treated by cardiac surgeons, whose management consisted of cutting only the intradermal part of the lead-electrodes followed by tissue curettage, leaving the other portion embedded in the subendocardium because its removal could cause serious complications. Dermatologists should be alert to such late complications of embedded permanent pacemakers. Their removal requires close cooperation with cardiac surgeons to avoid unexpected complications.

Aged↗

Establishment of an atopic dermatitis-like skin model in a hairless mouse by repeated elicitation of contact hypersensitivity that enables to conduct functional analyses of the stratum corneum with various non-invasive biophysical instruments.

BACKGROUND/AIMS: Pathogenesis of atopic dermatitis (AD) has been studied in animal models such as the NC/Nga mouse strain or Balb/C mice that are repeatedly treated with 2,4,6-trinitro-1-chrolobenzene (TNCB). These mice exhibit features of chronic contact dermatitis, including an intensified early type skin reaction, increased number of mast cells and elevated serum IgE levels with a shift of cutaneous cytokine expression from a type 1 to type 2 profile. However, it is difficult to investigate the unique skin changes of AD such as dry skin, barrier dysfunction, and increased turnover of the stratum corneum (SC) in these animals with biophysical instruments because of the presence of their fur coats. In this study, we succeeded in establishing a mouse model of AD in hairless mice that are suitable for various functional analyses of the SC as well as for examining the immunological characteristics of human AD by treating TNCB-contact sensitized hairless mice with 1% TNCB every other day for 36 days. METHODS: In hairless animals treated with TNCB every 2 days for 36 days, we measured time courses of skin swelling induced by contact hypersensitivity reaction on days 0, 6, 20 and 36. During the time course, non-invasive measurements for skin surface condition with biophysical instruments were conducted, and the area size and the rear surface villi of corneocytes obtained were measured. Also skin samples and blood samples were taken at each time point for histology and measurement of serum IgE level. RESULTS: A gradual intensification of an early type contact hypersensitivity reaction was observed over the treatment period. These mice exhibited reduced SC hydration, heightened trans-epidermal water loss, and increased skin thickness. These mice also showed a decrease in the surface area size of each corneocytes and marked villus formation on their rear surface. Histologically, there was an increase in the number of CD4 and CD8 positive T cells in the epidermis. Also observed was a marked increase in the number of dermal mast cells and eosinophils, which correlated with elevated serum IgE levels induced by TNCB treatments. CONCLUSIONS: From the results obtained we conclude that repeated treatments of TNCB-sensitized hairless mice with TNCB provides a useful means by which to study the pathological characteristics of AD skin lesions as well as their immunological characteristics.

Administration, Topical↗

CCR4 Expression by atypical T cells in systemic pilotropic lymphoma: its behavior under treatment with interferon gamma, topical PUVA and systemic retinoid.

We describe an 88-year-old Japanese patient with pilotropic T cell lymphoma involving the peripheral blood as well as lymph nodes. This patient presented with multiple red follicular papules, confluent, infiltrated erythematous plaques and nodules. Moreover, he was conspicuous for the presence of total alopecia of the scalp and eyebrows. Histopathologically, the lesional skin showed dense follicular and perifollicular infiltrates of atypical lymphocytes. The flow cytometry disclosed the presence of weakly CD4+ CCR4+ cell populations that would not be detected in the peripheral blood from healthy controls. The patient responded well to topical PUVA and systemic etretinate (retinoid-PUVA) and intravenous IFN-gamma. Parallel with the decrease in atypical cells in the peripheral blood, the percentage of weakly CD4+ CCR4+ T cells declined. However, about 1 week after we discontinued this treatment because of the side effects, the lymph node swelling became prominent, and, 4 weeks later, the patient died before restarting any specific chemotherapy.

Aged↗

12E2: a cloned murine dermal cell with features of dermal dendrocytes and capacity to produce pathologic changes resembling early Kaposi's sarcoma.

Factor XIIIa-positive dendrocytes are abundant within the dermis and have been implicated in the pathogenesis of various disorders, including AIDS-related Kaposi's sarcoma. Purified cultures of factor XIIIa-positive normal dermal dendrocytes have not as yet been achieved. 12E2 is a cloned cell line derived from superficial murine dermis where factor XIIIa-positive dendrocytes are abundant. Subconfluent cultures of 12E2 demonstrate polydendritic cell contours with thin, elongated membranous projections. These cells express Factor XIIIa and VCAM-1 by immunohistochemistry and by Western blot analysis of 12E2 cell lysates. 12E2 cells also constitutively express the Langerhans-cell-related epitope DEC-205, detected by NLDC-145 antibody and the CD80 co-stimulatory molecule, as well as Ia antigen on exposure to interferon-gamma. Cells so treated exhibit significant ability to present alloantigens in vitro. 12E2 cells are shown to express mRNA for numerous cytokines, including interleukin (IL)-1alpha, IL-1beta, IL-5, IL-6, IL-7, tumor necrosis factor-alpha and granulocyte macrophage-colony stimulating factor, by reverse-transcriptase polymerase chain reaction followed by Southern blot hybridization. Microinjection of 12E2 cells, but not 3T3control fibroblasts, into footpads of syngeneic and SCID mice results in lesions that mimic the histology and immunohistochemistry of human Kaposi's sarcoma. In aggregate, these data indicate that 12E2 cells 1) share lineage characteristics with factor XIIIa-positive dermal dendrocytes, 2) produce mRNA for numerous cytokines and are cytokine responsive to interferon-gamma, and 3) behave in vivo in a manner that resembles Kaposi's sarcoma, a condition known to involve proliferation of human dermal dendrocytes.

3T3 Cells↗

The safety assessment of fragrance materials.

Safety evaluation of the large number of diverse chemicals used as fragrance ingredients follows a systematic prioritization of data generation and analysis, consideration of exposure and critical analysis of the quality of the available information. In prior publications the research priorities used by the Research Institute for Fragrance Materials (RIFM), and the methods of exposure estimation used by industry have been summarized. This paper provides details of the approach used by the RIFM Expert Panel (REXPAN), to examine the dermal effects, systemic toxicity and environmental consequences of the use of and exposure to fragrance materials, which allow a reliable determination of safe use under intended conditions. The key to the usefulness of this analysis is the grouping of more than 2600 discrete ingredients into classes, based on chemical structures. Research sponsored by RIFM, data supplied by member companies, and relevant published reports from many sources are all considered during hazard characterization. A discussion is provided of REXPAN's decision tree approach to assessing the dermal, systemic and environmental endpoints and the types and quality of data included. This overall process results in well-documented conclusions which are provided to the International Fragrance Association (IFRA) as the basis for consideration of a new or existing Fragrance Material Standard and to industry for appropriate product risk management actions.

Consumer Product Safety↗

Ratio of immature cornified envelopes does not correlate with parakeratosis in inflammatory skin disorders.

We have previously established a non-invasive method to evaluate the maturity of cornified envelopes (CEs), and have reported the appearance of immature CEs in the stratum corneum (SC) with poor barrier function, such as the SC of the face. The purpose of the present study was to evaluate CEs in inflammatory skin disorders, and to clarify the relationship between the appearance of the immature CEs and parakeratosis, which is often used as a marker for defective keratinization in inflammatory skin disorders. Cornified envelopes in the outermost SC of involved areas of psoriasis vulgaris (PV) and atopic dermatitis (AD) were strikingly heterogeneous, and consisted of immature CEs stained with anti-involucrin and mature CEs stained with Nile red, whereas CEs of the uninvolved areas were relatively homogeneous, exhibiting mature phenotype. The ratio of immature CEs was significantly higher in the involved areas of PV and AD than that in the corresponding uninvolved areas, suggesting that defective CE maturation may, at least in part, account for the inflammatory disorders. Simultaneous evaluation of CE maturity and parakeratosis was carried out by a combination of involucrin immunostaining and nuclear staining of detergent-dissociated corneocytes. In the involved area of PV, four types of corneocytes in regard to the combination of involucrin staining and nuclear remnant were observed, while both immature CEs and parakeratosis were more often detected in the involved areas of PV than in the uninvolved areas or the upper arm of healthy subjects as a normal control. Thus, corneocytes with involucrin-positive immature CEs were not always associated with parakeratosis at the cellular level. In the involved areas of PV, the ratio of immature CEs and that of parakeratosis were heterogeneous, depending on the cases, and no correlation between the ratios was observed. Inter-individual and intraindividual variations in CE maturity were also suggested by the heterogeneous localization of involucrin in the psoriatic epidermis as examined by immunohistochemistry. In addition, in the face of healthy subjects, four types of corneocytes were similarly detected, and the ratio of immature CEs was significantly higher than that of parakeratosis. These results obviously suggest that the maturation of CEs and disappearance of nuclei are differentially regulated in the epidermis.

Cell Nucleus↗

Alteration in the production of IL-10 and IL-12 and aberrant expression of CD23, CD83 and CD86 by monocytes or monocyte-derived dendritic cells from atopic dermatitis patients.

Atopic dermatitis (AD) is characterized by the presence of Th2-type cells in the skin infiltration as well as in the peripheral blood, although a predominant infiltration of interferon-gamma (IFN-gamma)-producing cells is also reported in the chronic skin lesions of AD. Recently it has become clear that the development of Th1 or Th2 is strongly influenced by factors produced by the antigen presenting cells (APCs). To clarify whether APCs from AD patients play a favorable role in the differentiation of Th2 cells, we compared the production of cytokines and the expression of co-stimulatory molecules by monocytes (MOs) and monocyte-derived DCs (MoDCs) after stimulations with various reagents between 13 AD patients and 13 age-matched healthy controls. We examined their production of IL-1 beta, IL-10, IL-12p40, and IL-12p70, and their expression of CD23, CD40, CD54, CD80, CD83, CD86 and HLA-DR. We stimulated them with superantigens, lipopolysaccharide (LPS), agonistic anti-CD40 antibody, phytohemagglutinins (PHA), IL-1beta/TNF-alpha, IL-4, or IFN-gamma. The following results were obtained (1): IL-10 production was significantly enhanced in AD MOs after LPS stimulation. In contrast, IL-12p40 production was significantly lower in AD MOs than in HC MOs after a variety of stimulations (2). IL-12p40 was also significantly lower in AD MoDCs after LPS stimulation (3). The induction of CD23 with IL-4 was significantly higher in AD MOs. and finally (4), AD MoDCs augmented the expression of CD83, CD86, and HLA-DR less significantly than HC MoDCs after anti-CD40 Ab stimulation. These data indicate that AD APCs show some responses different from those observed in HC APCs after several stimulations, such as LPS, IL-1 beta/TNF-alpha, IL-4, or anti-CD40 Ab, and that these responses might play a role in the polarizing process of helper T cells into Th2 cells as recognized in AD patients.

Adolescent↗

Communication network in the follicular papilla and connective tissue sheath through gap junctions in human hair follicles.

Epithelial-mesenchymal interactions play a crucial role in the induction of life-long cyclic transformations of hair follicles. Many studies have already demonstrated several candidates for the soluble factors secreted from the mesenchymal components of the hair follicle, i.e. the follicular papilla (FP) and connective tissue sheath (CTS), which may be responsible for hair cycling. In this paper, we focused on cell-cell contact between FP cells (FPCs), between CTS cells (CTSCs), and between FPCs and CTSCs that may allow these mesenchymal components to function as a syncytium during hair cycling. Electron microscopic examination of the FP and the CTS obtained from human scalp revealed a tri-lamellar structure of the plasma membranes, which is a characteristic of gap junctions at the cell-cell contacting area. The immunohistochemical study with anticonnexin 43 Ab using a confocal laser scanning microscope demonstrated numerous spotted positive signals scattered throughout the FP. In the CTS, spotted positive signals were arranged linearly along the basement membrane of the hair follicle. In particular, these positive spots were aggregated in the transitional region between the FP and the CTS. By Western blot analysis of total protein extracts from the cultured FPCs and neonatal human dermal fibroblasts using anticonnexin 43 antibody, a positive band corresponding to connexin 43 was detected at 43 kDa on both the FPC lane and fibroblast lane. These findings suggest that the FP and the CTS form a communicating network through gap junctions, which may play a role in controlling the dynamic structural changes of hair follicles during hair cycling.

Adult↗

The "Haptic Finger"- a new device for monitoring skin condition.

BACKGROUND/AIMS: Touching the skin is of great importance for the Clinician for assessing roughness, softness, firmness, etc. This type of clinical assessment is very subjective and therefore non-reproducible from one Clinician to another one or even from time to time for the same Clinician. In order to objectively monitor skin texture, we developed a new sensor, placed directly on the Clinician's finger, which generate some electric signal when slid over the skin surface. MATERIAL AND METHODS: The base of this Haptic Finger sensor is a thin stainless steel plate on which sponge rubber, PVDF foil, acetate film and gauze are layered. The signal generated by the sensor was filtered and digitally stored before processing. In a first in vitro experiment, the sensor was moved over different skin models (sponge rubber covered by silicon rubber) of varying hardness and roughness. These experiments allowed the definition of two parameters characterizing textures. The first parameter is variance of the signal processed using wavelet analysis, representing an index of roughness. The second parameter is dispersion of the power spectrum density in the frequency domain, corresponding to hardness. To validate these parameters, the Haptic Finger was used to scan skin surfaces of 30 people, 14 of whom displayed a skin disorder: xerosis (n = 5), atopic dermatitis (n = 7), and psoriasis (n = 2). RESULTS AND CONCLUSION: The results obtained by means of the sensor were compared with subjective, clinical evaluations by a Clinician who scored both roughness and hardness of the skin. Good agreement was observed between clinical assessment of the skin and the two parameters generated using the Haptic Finger. Use of this sensor could prove extremely valuable in cosmetic research where skin surface texture (in terms of tactile properties) is difficult to measure.

Dermatology↗