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Biomedical subjects

H Tagami

Publications and source records attributed to H Tagami.

At least 91 records · Page 5Linked to original sources

A global repressor (Mlc) is involved in glucose induction of the ptsG gene encoding major glucose transporter in Escherichia coli.

Glucose stimulates the expression of ptsG encoding the major glucose transporter in Escherichia coli. We isolated Tn 10 insertion mutations that confer constitutive expression of ptsG. The mutated gene was identified as mlc, encoding a protein that is known to be a repressor for transcription of several genes involved in carbohydrate utilization. Expression of ptsG was eliminated in a mlc crp double-negative mutant. The Mlc protein was overproduced and purified. In vitro transcription studies demonstrated that transcription of ptsG is stimulated by CRP-cAMP and repressed by Mlc. The action of Mlc is dominant over that of CRP-cAMP. DNase I footprinting experiments revealed that CRP-cAMP binds at two sites centred at -40.5 and -95.5 and that Mlc binds at two regions centred around -8 and -175. The binding of CRP-cAMP stimulated the binding of RNA polymerase to the promoter while Mlc inhibited the binding of RNA polymerase but not the binding of CRP-cAMP. Gel-mobility shift assay indicated that glucose does not affect the Mlc binding to the ptsG promoter. Our results suggest that Mlc is responsible for the repression of ptsG transcription and that glucose modulates the Mlc activity by unknown mechanism.

Bacterial Proteins↗

A twenty-four-hour occlusive exposure to 1% sodium lauryl sulfate induces a unique histopathologic inflammatory response in the xerotic skin of atopic dermatitis patients.

Twenty-four-hour occlusive exposures of 1% aqueous sodium lauryl sulfate (SLS) produced unique functional and histological responses in patients with atopic dermatitis. Disruption of the stratum corneum barrier, measured by transepidermal water loss, was much greater and longer lasting than in normal controls. In contrast to controls the histologic pattern induced reproduced the typical features of the disease with spongiosis, exocytosis of mononuclear cells and a perivenular infiltrate containing eosinophils. The perivascular infiltrate consisted of CD1a+, CD4+ and HLA-DR+ cells, which was much greater and more persistent in atopics. Eosinophilic major basic protein was abundant in atopics but absent in controls. SLS provocation of atopic dermatitis is a striking experimental example of Koebnerization, in which disruption of the stratum corneum barrier as well as cytokine activation of keratinocytes reproduces the clinical diseases.

Adolescent↗

Phorbol 12-myristate 13-acetate can transform monocyte-derived dendritic cells to different cell types similar to those found in dermatofibroma. A possible in vitro model of the histogenesis of dermatofibroma.

Dermatofibroma is composed largely of interlacing fascicles of slender spindle cells set within a loose collagenous stroma and of scattered foamy histiocytes and multinucleated giant cells. There is clear evidence indicating that factor XIIIa+ dermal dendritic cells (DDCs) are the cells constituting dermatofibromas. However, it is still unknown what stimulation is responsible for transforming DDCs into different cell types, producing different subtypes of dermatofibromas. Recently, it has become possible to obtain dendritic cells (DCs), that are identical with DDCs in their phenotypic and functional characteristics, from the culture of CD14+ peripheral blood monocytes to which IL-4 and GM-CSF were added. Using these monocyte-derived DCs, we examined the ability of various cytokines, such as IL-1beta , IL-3, IL-5, IL-6, IL-7, IL-8, IL-10, TNFalpha, TGFbeta, M-CSF, IFNalpha, and IFNgamma, and phorbol 12-myristate 13-acetate (PMA), to induce different cell types observed in DFs. Among them, only PMA could induce a variety of cell types such as histiocytic cells, fibroblastic spindle-shaped cells, and even multinucleated giant cells of Touton or foreign body type. Phenotypically, all the induced cell types expressed CD1a, CD80, CD86, HLA-DR, and CD68 in a magnitude similar to that of non-treated monocyte-derived DCs. The expression of factor XIIIa was strongest in histiocytic cells, moderate in fibroblastic cells, and weakest or negative in giant cells. These data suggest that dermatofibromas are a kind of neoplastic disease which is induced only by the effect of some tumor promoter on DDCs.

Carcinogens↗

Solitary subcutaneous mucinosis surrounded by bizarre-shaped, factor XIIIa-positive cells with intranuclear vacuoles.

We describe a subcutaneous mucinosis developing in the right cheek of a 38-year-old man. Histologic examination revealed bipolar fibroblast-like cells embedded in a well demarcated mucinous stroma in the subcutis without a manifest reticulin network. In addition, bizarre, sometimes multinucleate, cells with intranuclear vacuoles were found at the periphery of the mucinous stroma. Immunohistologically, both the bipolar fibroblastic cells and bizarre-shaped cells were positive for vimentin, but were negative for smooth muscle A-actin, desmin, CD34, S100, trypsin, or chymotrypsin. However, the latter reacted to anti-factor XIIIa antibody, suggesting that they are derived from dermal dendritic cells. We think that this solitary subcutaneous mucinosis is a unique variant of cutaneous focal mucinosis, because neither a reticulin network nor reactivity to anti-smooth muscle A-actin antibody were demonstrable.

Adult↗

Release of monocyte chemoattractants by polymorphonuclear leukocytes stimulated by their adhesion to stratum corneum opsonized via complement activation, measured with a human acute monocytic leukemic cell line, THP-1.

Stratum corneum (SC) exposed to living tissues, induces inflammation characterized by the formation of mixed cell granulomas consisting of infiltrative polymorphonuclear leukocytes (PMNs) and monocytes/macrophages. In this study, to clarify the mechanism for the later monocyte accumulation in SC-induced granulomas, we evaluated monocyte chemotactic activity induced by PMNs treated with serum-opsonized SC by using a human acute monocytic leukemic cell line, THP-1. When the supernatant was obtained from a PMN suspension cultured with opsonized plantar SC, higher THP-1 chemotactic activity was detected as compared with that cultured with non-opsonized SC. Although some concentrations of the chemokines, MIP-1alpha and MIP-1beta, were detected in supernatants obtained from the PMN suspensions cultured with plantar SC than in the control suspensions of PMN alone, their production by PMN was not influenced by the opsonization procedure. In contrast, MCP-1 was found to be secreted from PMN suspensions constitutively, showing no correlation to this THP-1 chemotactic activity. Moreover, HPLC analysis of PMN suspensions indicated that factors with far higher molecular weight values than these chemokines are involved in the chemotaxis of THP-1 cells.

Cell Adhesion↗

An increased ratio of interleukin-1 receptor antagonist to interleukin-1alpha in inflammatory skin diseases.

IL-1 receptor antagonist (IL-1ra) is a cytokine that competitively binds the IL-1 receptor to antagonize IL-1 activity without any agonist function. Previous experiments indicated that the ratio of IL-1ra to IL-1alpha in the normal stratum corneum (SC) was much higher in the sun-exposed face than in the sun-protected area, upper arms. It was also reported by another laboratory that IL-1ra is increased in the lesional skin of psoriatic patients. This study was designed to measure the contents of IL-1alpha and IL-1ra in non-lesional and pathological SC obtained from inflammatory skin diseases including psoriasis and non-psoriatic dermatoses such as atopic dermatitis. The SC materials were obtained with a non-invasive tape-stripping method. Their soluble fractions were prepared and assayed for IL-1alpha and IL-1ra by enzyme-linked immunosorbent assays. As a result we confirmed the previous findings that the ratio of IL-1ra to IL-1alpha in the normal SC was much higher in the face than in the sun-protected sites, the trunk as well as extremities. Next, we found that IL-1alpha contents were significantly reduced in the SC samples obtained from inflammatory skin regardless of whether their IL-1ra contents increased or unchanged. Moreover, we noted that an increased ratio of IL-1ra to IL-1alpha in the SC was not specific to psoriasis, but was also found in other inflammatory skin diseases including atopic dermatitis. This ratio was found to become lower after successful treatment of these skin lesions with topical glucocorticoids. We conclude from these observations that the increased ratio of IL-1ra to IL-1alpha in the SC is a non-specific phenomenon that can occur in any inflammatory skin diseases regardless of the inflammatory pattern, probably reflecting a skin regulation process against various kinds of inflammation.

Dermatitis↗

Detection of human papillomavirus type 33 DNA in extragenital Bowen's disease with the polymerase chain reaction.

BACKGROUND: Data on the association of human papillomavirus (HPV) infection with extragenital Bowen's disease are very scarce. OBJECTIVE: To evaluate the prevalence of HPV infection in extragenital Bowen's disease showing histologically a number of koilocytes in the lesional epidermis, we studied formalin-fixed, paraffin-embedded tissues of 9 such cases. METHODS: HPV DNA was studied in such samples by the polymerase chain reaction (PCR) and in situ hybridization. RESULTS: Despite negative results with in situ hybridization, the PCR with HPV type 33 primer detected the presence of virus DNA in 2 out of 9 cases. CONCLUSION: As far as we know, this is the first report of the detection of HPV type 33 DNA in the lesional skin of extragenital Bowen's disease. The prevalence of HPV infection in extragenital Bowen's disease may be higher than expected, especially in cases histologically showing many koilocytes in the lesional epidermis.

Aged↗

Nonepisodic angioedema associated with eosinophilia: report of 4 cases and review of 33 young female patients reported in Japan.

BACKGROUND: In 1984, Gleich et al. described 4 patients with episodic angioedema associated with eosinophilia (EAE), which was characterized by recurrent episodes of angioedema and urticaria, eosinophilia, elevated serum IgM, fever, increased body weight and a benign course without involvement of the internal organs demonstrating that it was a clinical entity distinct from the hypereosinophilic syndrome. Thereafter, 37 cases of EAE have been reported in Japan, 33 cases of which, although similar, had a different evolution from classical EAE. OBJECTIVE: To describe 4 cases and review the cases of angioedema associated with eosinophilia reported in Japan. RESULTS: Four Japanese female patients had persistent angioedema mainly involving the hands and lower legs, and eosinophilia which resolved within a few months. The review of the 37 cases of EAE in the Japanese literature demonstrated that in 33 cases, there were common characteristics which differed from EAE. These included: (1) the absence of recurrent attacks; (2) the predominance of young females (20-37 years, with a mean of 26 years); (3) the localization of the angioedema to the extremities; (4) the absence of increase in the serum IgM level, and (5) the effectiveness of low-dose prednisone or even the occurrence of spontaneous remission. CONCLUSION: We propose that persistent angioedema with eosinophilia can be classified into 2 types, i.e. one being an episodic (recurrent) type as reported by Gleich and a nonepisodic type as our 4 cases and others found in the Japanese literature.

Adult↗

Effect of methylcarbonylmethyl 2(S)-[4-(4-guanidino-benzoyloxy)phenyl] propionate methanesulfonate (TT-S24) on experimental pancreatitis in rats.

The effect of methylcarbonylmethyl 2(S)-14-(4-guanidino-benzoyloxy) phenyl] propionate methanesulfonate (TT-S24) on experimental pancreatitis in rats was examined in comparison with that of camostat. TT-S24 showed a preventive effect on increases in plasma amylase activity and pancreatic weight induced by cerulein injection. TT-S24 also reduced an increase in plasma amylase activity induced by taurocholate. TT-S24 effectively prevented the mortality induced by an injection of a mixture of trypsin and taurocholate. TT-S24 showed no effect on an increase in amylase activity 6 h after duodenum ligation (closed duodenal loop pancreatitis), indicating that the drug had no effect on the initiation and propagation step of closed duodenal loop pancreatitis. On the other hand, TT-S24 reduced an increase in amylase activity 6 h after release of the duodenum ligation. TT-S24 showed anti-trypsin, anti-kallikrein, anti-thrombin and anti-plasmin activities. The effect of TT-S24 on some experimental pancreatitis models was nearly equal to or somewhat more potent in most instances to that of camostat. Therefore, TT-S24 should be useful in the clinical treatment of pancreatitis.

Amylases↗

Effect of methylcarbonylmethyl 2(S)-[4-(4-guanidinobenzoyloxy) phenyl] propionate methanesulfonate (TT-S24) on pancreatic secretion in rats.

The effect of methylcarbonylmethyl 2(S)-[4-(4-guanidinobenzoyloxy) phenyl] propionate methanesulfonate (TT-S24), a newly synthesized trypsin inhibitor, on exocrine pancreatic secretion was examined and compared with that of camostat in rats. Intraduodenal (i.d.) administration of TT-S24 and camostat resulted in an increase in volume, amylase concentration and amylase output of pancreatic juice. Although i.v. injection of TT-S24 and camostat (3 mg/kg) had no effect on the pancreatic juice volume, TT-S24 (i.v.) dose-dependently increased pancreatic juice volume under acetylcholine (10 micrograms/kg/min) infusion. In addition, the weight of pancreases from WBN rats was significantly increased by 28 day oral administration of TT-S24 (100 mg/kg) with a potency similar to that observed with camostat.

Acetylcholine↗

Annular elastolytic sarcoidosis of the face.

We report a case of facial annular lesions in a non-diabetic, Japanese woman aged 78, the histopathological study of which showed noncaseating, epithelioid cell granuloma with multinucleated giant cells. Together with the aberrant laboratory data, these clinical and histopathological findings were considered to be compatible with those of sarcoidosis, but elastic tissue stain disclosed the existence of elastolytic changes which were clinically and histopathologically similar to those found in actinic granuloma or annular elastolytic giant cell granuloma. Based on a review of the literature, we believe that several annular elastolytic granulomatous diseases of the face form a disease spectrum, some of which are identified with intermediate features of these three diseases.

Aged↗

Construction of a contiguous 874-kb sequence of the Escherichia coli -K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features.

The contiguous 874.423 base pair sequence corresponding to the 50.0-68.8 min region on the genetic map of the Escherichia coli K-12 (W3110) was constructed by the determination of DNA sequences in the 50.0-57.9 min region (360 kb) and two large (100 kb in all) and five short gaps in the 57.9-68.8 min region whose sequences had been registered in the DNA databases. We analyzed its sequence features and found that this region contained at least 894 potential open reading frames (ORFs), of which 346 (38.7%) were previously reported, 158 (17.7%) were homologous to other known genes, 232 (26.0%) were identical or similar to hypothetical genes registered in databases, and the remaining 158 (17.7%) showed no significant similarity to any other genes. A homology search of the ORFs also identified several new gene clusters. Those include two clusters of fimbrial genes, a gene cluster of three genes encoding homologues of the human long chain fatty acid degradation enzyme complex in the mitochondrial membrane, a cluster of at least nine genes involved in the utilization of ethanolamine, a cluster of the secondary set of 11 hyc genes participating in the formate hydrogenlyase reaction and a cluster of five genes coding for the homologues of degradation enzymes for aromatic hydrocarbons in Pseudomonas putida. We also noted a variety of novel genes, including two ORFs, which were homologous to the putative genes encoding xanthine dehydrogenase in the fly and a protein responsible for axonal guidance and outgrowth of the rat, mouse and nematode. An isoleucine tRNA gene, designated ileY, was also newly identified at 60.0 min.

Base Sequence↗

Dendritic cells differently respond to haptens and irritants by their production of cytokines and expression of co-stimulatory molecules.

After application of haptens to the skin, Langerhans cells (LC), i.e. immature dendritic cells (DC) in the skin, move to secondary lymphoid organs to sensitize naive T cells. During this process, LC become mature DC with augmented expression of various co-stimulatory molecules and MHC class II antigens. In this scenario, however, critical questions remain as to what kind of chemicals can induce this maturation process through what kind of mechanisms. To clarify these questions, we used monocyte-derived CD1a+ DC instead of LC since LC maturated spontaneously in vitro culture. After we confirmed that monocyte-derived DC showed at least phenotypic characteristics and a response to TNF-alpha similar to LC, we added various chemicals, i.e., dinitrochlorobenzene (DNCB), trinitrochlorobenzene (TNCB), NiCl2, ZnCl2, sodium dodecyl sulfate (SDS), or benzalkonium chloride (BC), to a culture of purified monocyte-derived CD1a+ DC. Of these chemicals, only NiCl2 and DNCB significantly increased the surface expression of CD54, CD86, HLA-DR antigen, and interleukin (IL)-1 beta production, while SDS, BC, or ZnCl2 could not augment them, except for weak augmentation of CD86 expression by SDS. The increase in the expression of CD86 induced by NiCl2 or DNCB was most remarkable, being observed in DC from almost all the subjects we examined. TNCB could also induce responses similar to those induced with DNCB, but the number of subjects whose DC responded to it was far less than that of subjects whose DC responded to NiCl2 or DNCB. In spite of the augmented CD86 expression on DC treated with DNCB or NiCl2, these chemicals induced different responses of DC in their expression of CD54 and HLA-DR and the production of IL-6 and tumor necrosis factor (TNF)-alpha. In addition, the up-regulation of CD86 expression on DC treated with DNCB was significantly suppressed by either anti-IL-1 beta or anti-TNF-alpha antibody, while that by NiCl2 was relatively insensitive to these antibody treatments. Finally, the protein kinase C inhibitor, H7, but not staurosporine, could suppress the augmentation of CD86 expression on DC induced either by NiCl2 or by DNCB. These data suggest that DC respond to some haptens by changing their expression of several co-stimulatory molecules and their production of cytokines with a resultant change in antigen-presenting function. They also suggest that these chemicals stimulate DC by different mechanisms. By these responses, DC may modulate the final immune response to chemicals.

Antibodies↗

Dehydroepiandrosterone may be one of the regulators of cytokine production in atopic dermatitis.

Previous studies in mice have shown that dehydroepiandrosterone (DHEA) increases the production of Th1-associated lymphokines, and of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), by lymphocytes. However, there are no reports concerning the effect of DHEA on the production of Th2-associated lymphokines, IL-4 and IL-5, by lymphocytes in humans. We examined serum DHEA levels in patients with atopic dermatitis (AD), which is thought to be associated with a higher activity of Th2 cells than of Th1 cells. We also studied the effects of DHEA on the production of IL-4 and IL-5 by human lymphocytes. Serum DHEA concentrations in 47 adult male patients with AD aged 19-30 years were significantly lower than those of 53 age-matched healthy male controls. Preincubation of peripheral blood mononuclear cells (PBMCs) with DHEA reduced the IL-4 production by concanavalin A-stimulated PBMCs. Their IL-5 production also showed a tendency to decrease. These results suggest that DHEA may be one of the regulators of IgE synthesis and eosinophil proliferation in patients with AD and it may act by controlling IL-4, IL-5 and IL-2 production by lymphocytes.

Adult↗

C3 production of cultured human epidermal keratinocytes is enhanced by IFNgamma and TNFalpha through different pathways.

We investigated the regulation of C3 production by human cultured epidermal keratinocytes by enzyme-linked immunosorbent assay. The results showed that IFNgamma and TNFalpha enhanced the synthesis of C3 by epidermal keratinocytes in a concentration-dependent manner. Moreover, a protein kinase C (PKC) inhibitor blocked C3 production, whereas PMA enhanced it. There was a synergistic effect between IFNgamma and TNFalpha. In experiments to investigate the role of protein tyrosine kinase (PTK) in C3 production, we found that treatment with herbimycin A, a specific inhibitor for the c-Src-related PTK, caused significant enhancement of the C3 production induced by IFNgamma or TNFalpha, suggesting that c-Src-type PTK(s) provides a negative signal to C3 production. Each competitive inhibitor of PTK, genistein or tyrphostin, substantially increased the C3 production by IFNgamma at lower concentrations, although each agent had little effect on TNFalpha-associated production of C3 at the same concentrations. The data show that pro-inflammatory cytokines IFNgamma and TNFalpha synergistically augment C3 production by epidermal keratinocytes by different pathways.

Cells, Cultured↗