Successful treatment of dissecting cellulitis and acne conglobata with oral zinc.
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Biomedical subjects
Publications and source records attributed to H Tagami.
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The significance of the association of malignant diseases with bullous pemphigoid is still unknown. We report a case of squamous cell carcinoma of the skin associated with both bullous pemphigoid and vitiligo. It is possible that there is a common underlying pathogenic mechanism involved in the co-existence of these three skin diseases as successful treatment of the carcinoma was accompanied by resolution of the bullous pemphigoid and improvement of the vitiligo.
BACKGROUND: The pts operon of Escherichia coli consists of three genes ptsH, ptsI and crr, each encoding for central components of the phosphoenolpyruvate: carbohydrate phosphotransferase system, HPr, enzyme I and IIAGlc, respectively. Transcription of the pts operon is stimulated when glucose is present in the culture medium. One of the two major promoters, P0, is responsible for this glucose induction. However, no regulatory protein responsible for the glucose induction of the pts operon has been identified yet and molecular mechanism by which glucose stimulates the pts transcription is not known. RESULTS: We found by Northern blotting that the pts mRNA levels in cells lacking Mlc, a new global repressor of carbohydrate metabolism, were increased without external glucose and that the addition of glucose had no effect on the pts mRNA levels in the mutant cells. Western blotting revealed that the enzyme I level in the mlc- cells was also elevated without glucose and no further increase in the enzyme I level was observed in the presence of glucose. S1 analysis revealed that transcription of the glucose-sensitive promoter, P0, occurs constitutively in the mlc- cells independently from the external glucose. In vitro transcription studies indicated that Mlc strongly inhibited P0 transcription. DNase I footprinting experiment revealed that Mlc bound to P0 promoter region to prevent RNA polymerase binding at P0. CONCLUSION: We conclude that Mlc is a repressor for the pts transcription acting as a major regulatory protein involved in the glucose induction of pts operon. We propose that glucose induces the pts transcription by modulating the Mlc activity. The mechanism by which glucose modulates the Mlc action remains to be studied.
As is well known in the case of Langerhans cells, dendritic cells (DCs) play a crucial role in the initiation of immunity to simple chemicals such as noted in the contact hypersensitivity. Because DCs are scattered in non-lymphoid organs as immature cells, they must be activated to initiate primary antigen-specific immune reactions. Therefore, we hypothesized that some simple chemicals must affect the function of DCs. In this paper, we first demonstrated that human monocyte-derived DCs responded to such simple chemicals as 2, 4-dinitrochlorobenzene (DNCB), 2,4,6-trinitrochlorobenzene (TNCB), 2, 4-dinitrofluorobenzene (DNFB), NiCl2, MnCl2, CoCl2, SnCl2, and CdSO4 by augmenting their expression of CD86 or human leucocyte antigen-DR (HLA-DR), down-regulating c-Fms expression or increasing their production of tumour necrosis factor-alpha (TNF-alpha). In addition, the DCs stimulated with the chemicals demonstrated increased allogeneic T-cell stimulatory function. Next, we found that, among these chemicals, only NiCl2 and CoCl2 induced apoptosis in them. Finally, we examined the effects of these chemicals on CD86 expression by three different macrophage subsets and DCs induced from the cultures of human peripheral blood monocytes in the presence of macrophage colony-stimulating factor (M-CSF), M-CSF + interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and GM-CSF + IL-4, respectively. Among them, only DCs dramatically augmented their expression of CD86. These observations have revealed unique characteristics of DCs, which convert chemical stimuli to augmentation of their antigen presenting function, although their responses to different chemicals were not necessarily uniform in the phenotypic changes, cytokine production or in the induction of apoptosis.
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BACKGROUND: The plantar surface is one of the commonest sites of malignant melanoma in the Japanese; however, the biological behavior is not sufficiently clarified, because of the paucity of long-term studies. We attempted an epidemiologic survey of the cases of plantar melanoma treated in our institute to study the survival rate in the recent period. METHODS: Of the 207 cases of malignant melanoma observed over the past 28 years, 62 patients were diagnosed as having plantar melanoma. The proportion of plantar melanoma to all melanomas, the sex and age of the patients, and the histologic type, stage, and prognosis were evaluated by comparing those registered in the first half (1969-1982) and the second half (1983-1996) of the period. RESULTS: The proportions of plantar melanoma in the first and second half periods were 31% (28 out of 90) and 29% (34 out of 117), respectively. No sex difference in the patients was observed. The mean age of the patients was 67 years. Fifty-one lesions were histologically proven to be acral lentiginous melanoma (ALM), two were superficial spreading melanoma (SSM), and nine were nodular melanoma (NM). Of the nine NMs, eight were registered in the second half period. The heel was affected in 33 (53%), the metatarsal regions in nine (14%), the toes in six (10%), and the arch areas in 14 (23%). The proportion of the weight-bearing areas, including the heel, metatarsal areas, and toes, decreased in the second half period. A comparison of the stages of plantar melanoma showed that, in the first half period, there were 18% of patients with stage IV disease in contrast to none in the second half period. Conversely, the proportion of stage I and II disease was 50% in the second half period, whereas it was only 39% in the first half period. The 5-year survival rates in the first and second half periods were 56% and 71%, respectively. CONCLUSIONS: The prognosis of plantar melanoma has improved recently at our institute. The possible explanation for a trend to better survival in the second half period may be related to a decrease in stage IV disease as well as to an increase in the frequency of diagnosis of early stage disease.
Hand washing is an indispensable procedure for surgical nurses. Although scrubbing up with a brush is preferable to prevent infections, it is not clear how irritating to the skin scrubbing with a brush is compared with hand washing without a brush. TEWL, high frequency conductance and pH were measured on the hand skin of the same group of nurses before and after daily hand washing for 11 days in different seasons, which were chosen as favourable and unfavourable periods for the condition of hand skin, namely the early summer and autumn. Additionally, we compared the antimicrobial effects on the skin of scrubbing up, using a palm stamp method. TEWL showed significantly higher values with brush washing than with simple hand washing only in the autumn. There was no significant difference in the measurement of high frequency conductance, pH or in the antimicrobial effects between the two washing techniques. Results showed the deleterious effects on the skin of hand washing, particularly that of using a brush in the cold season.
BACKGROUND: The pathogenesis of nummular eczema (NE) is still unknown. It often develops on the lower legs of elderly individuals with xerotic changes during the winter months. Such winter exacerbation is also observed in atopic dermatitis, in which there is a high incidence of cutaneous immune reactivities against environmental aeroallergens. OBJECTIVE: Because of the total lack of information about skin reactivities in NE patients, we performed immunological as well as functional studies in their uninvolved skin. METHOD: Prick tests and chamber scarification patch tests for representative aeroallergens were conducted on the flexor surface of the forearm in 26 NE patients, in 21 age-matched elderly persons without NE and in 43 healthy young controls. RESULTS: We found that the elderly subjects, regardless of their background, showed a significantly higher immediate skin reactivity to Candida albicans than the young controls. In contrast, patch testing revealed that, unlike the age-matched elderly subjects who showed a decrease in incidence of positive patch test reactions, the NE patients retained delayed contact sensitivity at a level comparable to that of the young healthy controls. They showed a significantly higher percentage of positive patch test reactions to Dermatophagoides farinae allergen (46%) and house dust allergen (35%) than the age-matched controls. Moreover, they also showed a significantly higher percentage of delayed hypersensitive reactions to C. albicans allergen (85%) than the age-matched controls (48%). Noninvasive functional assessment of the stratum corneum (SC) in unaffected skin areas of the lower legs in 8 NE patients demonstrated that, though the water barrier function of the SC was comparable to that of the age-matched controls, they showed a significantly lower hydration state of the SC than the age-matched controls. CONCLUSION: The xerotic skin of elderly individuals facilitates the development of cracking and fissuring of the skin surface in dry and cold winter. Such damage in the SC is sometimes aggravated by inadvertent scratching due to pruritus, allowing skin permeation of various environmental allergens. They may induce eczematous changes in those with preserved adequate delayed hypersensitivity despite their advanced age.
Initiation and aggravation of several inflammatory skin diseases are associated with Malassezia furfur. These are divided into at least two groups. In one group including tinea versicolor and Malassezia folliculitis, the growth of Malassezia furfur directly triggers the development of the cutaneous lesions. In another group including atopic dermatitis, seborrheic dermatitis, and psoriasis, cutaneous lesions already developed by other mechanisms are aggravated by the growth of Malassezia furfur. Recent progress of molecular biology techniques revealed that Malassezia furfur is divided into at least seven species. Since their clinical and histological findings are quite diverse, their differences cannot be explained solely by the difference in antigenicity of each Malassezia. Instead, the cutaneous defense mechanisms against Malassezia furfur must be considered. In this article, we reviewed the mechanisms at three levels: 1) barrier functions of the uppermost layer of the skin, the stratum corneum, 2) cytokine production by epidermal keratinocytes, and 3) immune and inflammatory responses by infiltrating neutrophils and T cells.
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We have shown previously that the cyclic AMP receptor protein (CRP) is not required after the formation of the open complex at the lac promoter (Tagami and Aiba, 1995, Nucleic Acids Res., 19, 6705-6712). In this paper, we investigate the role of CRP in transcription activation at the malT and gal promoters. At the malT promoter, RNA polymerase (RNAP) forms a nonproductive RNAP-promoter binary complex in the absence of CRP and a productive CRP-RNAP-promoter ternary complex in the presence of CRP. CRP can be removed from the malT ternary complex by a moderate concentration of heparin. The resulting binary complex is functionally identical to the ternary complex. At the gal promoter, RNAP predominantly forms a binary complex at the P2 promoter in the absence of CRP and a ternary complex at the P1 promoter in the presence of CRP. A very high concentration of heparin is able to dissociate CRP from the galP1 ternary complex without changing the properties of the complex. These data indicate that CRP is not required for the maintenance of the ternary complex and plays no role in the subsequent steps, irrespective of the promoter. We conclude that the common role of CRP in the activation of transcription is to stimulate events leading to the formation of a productive open complex at a diverse set of CRP-dependent promoters. We suggest that the interaction between CRP and RNAP is needed only transiently for the activation of transcription.
PAX6 is a candidate gene for familial aniridia. We have carried out a mutational analysis of the PAX6 gene in a three-generation family from Germany, containing 5 individuals affected with ocular abnormalities. In all affected individuals, a heterozygous mutation was detected in the PAX6 gene, exchanging tyrosine 369 by a stop codon. The mutation is located in the 3' moiety of the PST domain, at the C terminus of the PAX6 protein. In the affected family members, the same heterozygous mutation leads to distinct phenotypes of varying severity. Most notably, no aniridia was observed in one of the family members carrying the mutation, although other ocular abnormalities (underdeveloped iris and cataracts) were present. We discuss the possibility that small C terminal truncations of the PAX6 protein might lead to less severe or more divergent phenotypes than trancations at internal positions.
A number of studies have demonstrated an increased frequency of allergen-specific T cells producing increased amounts of interleukin-4 (IL-4) and IL-5, but little interferon-y in both the peripheral blood and skin lesions of patients with atopic dermatitis (AD). In this study, to further clarify the characteristics of T cells obtained from AD patients, we examined the dependency of the antigen-specific proliferation of peripheral blood mononuclear cells (PBMC) from AD patients on costimulatory molecules. The antigens used were Candida albicans and Dermatophagoides farinae, for which AD patients show increased levels of IgE antibodies. PBMC from control healthy donors stimulated with these antigens incorporated [3H]-thymidine much more than PBMC from AD patients. The addition of anti-CD54, -CD40, -CD80 and -CD86 monoclonal antibodies to the cultures showed that the PBMC required only CD54 and CD86 for stimulation with C. albicans, but required CD54, CD80 and CD86 for stimulation with D. farinae. Among these monoclonal antibodies, the anti-CD54 antibody suppressed the proliferative responses of most PBMC, most effectively followed by the anti-CD86 antibody. However, there were no significant differences in the requirement for costimulatory molecules of PBMC proliferation stimulated with C. albicans or D. farinae between AD patients and healthy donors. Since many studies have suggested that T-helper type 1 and T-helper type 2 immune responses are different in their dependency on CD80 or CD86 costimulation, our present results suggest that the allergen-specific T cells of AD patients are not completely shifted to a T-helper type 2 subset.
We describe tufted hair folliculitis that developed in a chronically erosive plaque on the scalp of a Japanese man patient with pemphigus vulgaris. After repeated intralesional corticosteroid injections, the erosive lesion improved, leaving multiple hairs emerging from single follicular openings. The current case suggests that localized exudative inflammatory lesions in the scalp regardless of cause can result in tufted hair formation.
In eukaryotes, de novo synthesis of proteins is mainly under control at the level of gene transcription by nuclear transcription factors with unique protein motifs such as leucine-zipper and zinc-finger. Binding of radiolabeled oligonucleotide probes for the "leucine-zipper" transcription factors, including activator protein-1 (AP1) and cyclic AMP response element binding protein (CREB), was markedly reduced in nuclear extracts of the adrenals from mice sacrificed 2 h after the subcutaneous injection of triamcinolone acetonide (TA), an agonist at glucocorticoid (GC) receptors which are also a transcription factor with "zinc-finger" motifs. The reduction was most significant 2 h after the administration, with recovery to the control level within 7 h after the injection. Moreover, the administration of TA invariably doubled immunoreactivities to an antibody against human GC receptors in nuclear fractions of the adrenal, pituitary and hypothalamus, with a concomitant reduction of those in cytosol fractions. Similar inhibition by TA was also seen with AP1 binding in the pituitary, while TA did not affect binding of radioprobes for AP1 and CREB in any discrete brain structures. These results suggest that systemic TA signals may be preferentially transduced into cell nuclei to attenuate DNA binding activities of AP1 through molecular mechanisms associated with crosstalk between transcription factors with different protein motifs in murine peripheral but not central excitable tissues.
Before the establishment of procedures to cultured dendritic cells (DCs) from peripheral blood or bone marrow progenitor cells using a combination of several cytokines, Langerhans cells (LCs) of the epidermis have been used as the best characterized dendritic cell population. The studies using LCs freshly isolated from the skin or DCs from the blood or spleen and cultured DCs from progenitors have elucidated that although DCs are a unique cell population characterized by their potent antigen presenting function, especially by their induction of primary antigen-specific T cell responses, they are immature and less potent in antigen presenting function immediately after isolated from the skin or from other non-lymphoid tissues. Therefore, DCs must be stimulated to augment their antigen presenting function and to initiate a naive T cell response. Recently, it becomes clear that a variety of signals, such as microorganisms, cytokines, adhesion to extracellular matrix, and simple chemicals like haptens, can induce this activation process in DCs, which is also called as DC maturation. In this paper, we discuss what kinds of stimuli effectively activate DCs.
The strong association of acute guttate psoriasis and streptococcal throat infection, together with the preferential use of T cells expressing a particular T-cell receptor, has suggested a role for bacterial superantigens in the pathogenesis of psoriasis. We examined the proliferative responses of peripheral blood lymphocytes (PBLs), obtained from patients with psoriasis and from healthy controls, to streptococcal superantigens, cytoplasmic membrane-associated protein (CAP) and secretion-type CAP (SCAP), isolated from group A, beta-haemolytic streptococci. PBLs from patients with psoriasis showed significantly less response to SCAP and CAP than those from healthy controls. Because there was no difference between psoriatic patients and controls in the proliferative response of PBLs to staphylococcal enterotoxin A or E (SEA, SEE) or the mitogen phytohaemagglutinin (PHA), these findings strongly suggest that the reduced reactivity to the streptococcal superantigens seems to reflect anergy of a population of PBLs to the superantigens. As the CAP used in the present study stimulates V beta 8 T cells selectively, we further examined the proliferation of V beta 8 T cells after such stimulation using flow cytometry. V beta 8 T cells obtained from three of four psoriatic patients failed to proliferate in the presence of CAP, whereas they proliferated vigorously in the presence of SEE, which activates V beta 8 T cells, confirming the specific hyporesponsiveness of PBLs from psoriatic patients to streptococcal superantigens. We then determined the effects of serum factors on the suppressed response of PBLs to the streptococcal superantigens with SCAP or CAP. It was partially restored when PBLs were cultured with sera obtained from healthy subjects, although the responses were still significantly lower than those of the healthy controls. In contrast, psoriatic sera markedly suppressed the proliferative response of PBLs from healthy controls to CAP or SCAP, but showed no suppression of the proliferative response of PBLs to SEA. Because these findings suggest the presence of specific inhibitory factors in psoriatic sera, we examined whether the inhibitory effect was caused by antisuperantigen antibody. However, no significant increase was detected in antibody titre to CAP in psoriatic sera, as has been noted in sera from patients with poststreptococcal glomerulonephritis. The present results show for the first time the hyporesponsiveness of PBLs to streptococcal superantigens and the presence of serum inhibitors that specifically inhibit T-cell response to the superantigens in psoriatic patients. These findings suggest a pathological role for streptococcal infections in the pathogenesis of psoriasis.
Recent studies of the stratum corneum (SC) in patients with atopic dermatitis (AD) have disclosed various functional impairments even in clinically unaffected skin. However, it has not been clear whether the presence of atopic background itself has any influence on the function of the SC. In this study, we conducted functional studies of the SC in the mid-portion of the flexor surface of the forearm of 49 skin lesion-free patients with allergic rhinitis to Japanese cedar pollen (atopic respiratory disease; ARD) in early spring, their disease-active season, by comparing the findings obtained with those in 28 patients with AD and 57 age-matched healthy control subjects. The results showed that the patients with ARD had significantly lower skin surface hydration levels assessed by high-frequency conductometry than those of the healthy control subjects. These levels were, however, not as low as those noted in moderately or severely affected patients with AD. Moreover, by measuring the amounts of water-soluble amino acids contained in the superficial portions of the SC, we found that these are also decreased at a marginal level (P = 0.051) in patients with ARD compared with levels in healthy control subjects. In contrast, the water barrier function of the SC evaluated by measurements of transepidermal water loss in patients with ARD was not different from that of the healthy control subjects. These results suggest that, although their skin appears normal clinically, the SC of the patients with ARD has functional deficiency in water-holding capacity.