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Biomedical subjects

H Torii

Publications and source records attributed to H Torii.

At least 37 records · Page 2Linked to original sources

Predicting the effects on patients with dilated cardiomyopathy of beta-blocker therapy, by using iodine-123 15-(p-iodophenyl)-3- R,S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy.

We examined whether the iodine-123 15-(p-iodophenyl)-3- R,S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy was useful for predicting the treatment response to beta-blocker in patients with dilated cardiomyopathy (DCM). Sixteen patients with DCM were studied. BMIPP single photon emission computed tomography (SPECT) was performed before beta-blocker therapy. The count ratio of the heart (H) to the upper mediastinum (M) (H/M ratio) was calculated. Several measurements including the BMIPP H/M ratio before the administration of metoprorol were retrospectively compared among the 10 "good responders" (showing improvement by at least one NYHA class or an increase in the ejection fraction of > or = 0.10, 6 months after the start of the drug therapy) and the 6 "poor responders." The bull's eye map of BMIPP was divided into 17 areas. Each segmental score was analyzed quantitatively by means of a two-point scoring system (good uptake > or = 67%, poor uptake < 67%). The total score was regarded as the uptake score. The H/M ratio was significantly higher in the good responders than in the poor responders (2.41 +/- 0.24 vs. 1.86 +/- 0.17 p < 0.01). There were no significant differences between the two groups in any other variable data at entry. The uptake score was also a good index for predicting the therapeutic effect. When a relative uptake of 67% or higher was scored as 1, uptake scores of 9 to 17 corresponded to good responses (sensitivity = 100%, specificity = 100%, accuracy = 100%, positive and negative predictive value = 100%). Although the number of patients studied is small, our results suggests that BMIPP myocardial scintigraphy can predict the response to a beta-blocker in patients with DCM.

Adrenergic beta-Antagonists↗

The effect of neuropeptides/hormones on Langerhans cells.

Neuropeptides/hormones have been shown to regulate the various functions of many immunocompetent cells. A number of neuropeptides/hormones has been demonstrated to be present in the skin and a close anatomical association between calcitonin gene-related peptide (CGRP)-containing nerves and Langerhans cells (LC) has been reported. In addition to the CGRP receptor, receptors for several neuropeptides including pituitary adenylate cyclase activating polypeptide (PACAP) and gastrin releasing peptide (GRP) are found on LC, suggesting these neuropeptides might have some effects on LC. CGRP inhibits alloantigen presentation and stimulation of a specific-antigen responsive T-cell clone by LC. Pre-treatment of LC with CGRP also inhibits the elicitation of delayed type hypersensitivity (DTH) in tumor immune mice. Upregulation of B7-2 expression on LC is suppressed by CGRP, which might be, in part, responsible for the inhibitory effect of CGRP in the functional assay. The production of some inflammatory cytokines such as IL-10 by LC-like cell line XS52 is regulated by CGRP and the functional effect of CGRP appears to be at least partially mediated through the autocrine regulation of IL-10. Alpha-MSH is another neuropeptide, the effect of which has been well studied in the cutaneous immune system. Pre-treatment of mice with alpha-MSH produces inhibitory effects in contact hypersensitivity (CHS). IL-10 has been suggested to be involved in the inhibitory effect of alpha-MSH. The receptors and the functional effects of other proopiomelanocortin (POMC)-derived peptides including beta-endorphin and catecholamines on LC are under investigation.

Animals↗

Dendritic cells genetically modified with an adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity.

Dendritic cells (DCs) are potent antigen-presenting cells that play a critical role in the initiation of antitumor immune responses. In this study, we show that genetic modifications of a murine epidermis-derived DC line and primary bone marrow-derived DCs to express a model antigen beta-galactosidase (betagal) can be achieved through the use of a replication-deficient, recombinant adenovirus vector, and that the modified DCs are capable of eliciting antigen-specific, MHC-restricted CTL responses. Importantly, using a murine metastatic lung tumor model with syngeneic colon carcinoma cells expressing betagal, we show that immunization of mice with the genetically modified DC line or bone marrow DCs confers potent protection against a lethal tumor challenge, as well as suppression of preestablished tumors, resulting in a significant survival advantage. We conclude that genetic modification of DCs to express antigens that are also expressed in tumors can lead to antigen-specific, antitumor killer cells, with a concomitant resistance to tumor challenge and a decrease in the size of existing tumors.

Adenocarcinoma↗

Regulation of cytokine expression in macrophages and the Langerhans cell-like line XS52 by calcitonin gene-related peptide.

Calcitonin gene-related peptide (CGRP) inhibits antigen presentation by Langerhans cells (LC) and macrophages, and LC are anatomically associated with CGRP-containing epidermal nerves. To determine whether CGRP may produce some of its functional effects through regulation of cytokine expression, we utilized enzyme-linked immunosorbent assay (ELISA) of conditioned supernatants to examine production of interleukin (IL)-10 and IL-1 beta protein in the LC-like cell line XS52 as well as the reverse transcriptase-polymerase chain reaction (RT-PCR) to examine levels of mRNA for IL-10, IL-1 beta, and the 40-kDa subunit (p40) of IL-12. CGRP augmented the lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF) -induced release of IL-10 protein and the induced expression of IL-10 mRNA in these cells. However, it suppressed the induction of release of IL-1 beta protein and the induction of mRNA for IL-12 p40 and IL-1 beta by LPS and GM-CSF. Regulation of cytokine expression in peritoneal macrophages was also examined. By ELISA, the LPS-induced expression of IL-10 was augmented by CGRP, whereas the induction of IL-1 beta was suppressed. Northern analysis demonstrated augmentation of LPS-induced IL-10 mRNA levels and inhibition of LPS-induced IL-1 beta mRNA by CGRP. CGRP inhibited the LPS-induced induction of IL-12 mRNA as assessed by RT-PCR. Up-regulation of B7-2 expression by LPS and GM-CSF was suppressed by CGRP in both XS52 cells and macrophages, as previously reported. This suppression, however, could be abrogated by co-culture with neutralizing antibodies to IL-10. Furthermore, the presence of neutralizing antibodies to IL-10 during exposure of epidermal cells (EC) to CGRP prevented the CGRP-mediated suppression of EC presentation of tumor-associated antigens (from the S1509a spindle cell carcinoma) for elicitation of delayed-type hypersensitivity in S1509a-immune mice. These data suggest that suppression of antigen-presenting function by CGRP is mediated, at least in part, by changes in cytokine expression that favor less robust antigen presentation for cell-mediated immunity.

Animals↗

Calcitonin gene-related peptide and Langerhans cell function.

Morphologic studies have indicated that Langerhans cells (LC) are frequently in anatomic apposition with epidermal nerves containing the neuropeptide calcitonin gene-related peptide (CGRP). Experiments were undertaken to examine whether CGRP modulates LC function. The effect of pre-exposure of LC to CGRP in vitro on alloantigen presentation and specific protein presentation to a responsive T-cell line were studied using freshly prepared murine epidermal cell populations enriched for LC content (EC) by treatment with antibody to Thy-1 and complement. The ability of EC to present tumor-associated antigens for induction and elicitation of delayed-type hypersensitivity (DTH) in tumor-immune mice was also examined. Inhibitory effects of CGRP on antigen presentation were observed in each of these assays. Experiments were also performed examining the ability of intradermally administered CGRP to modulate induction of contact hypersensitivity (CHS) to a hapten applied at the injected site. Administration of CGRP led to a decrease in the CHS response after immunization at the site of injection. Intracellular cAMP was significantly increased in freshly prepared LC after exposure to CGRP, and this process could be inhibited by a specific inhibitor of the CGRP receptor, demonstrating the existence of CGRP receptors on LC. B7-2 expression induced by LPS and GM-CSF in the LC-like line XS52, and by LPS in peritoneal macrophages, was suppressed by CGRP. This suppression may account, in part, for the inhibitory effect of CGRP. As a whole, these observation suggest that regulation of antigen presentation by nerves may occur in the epidermis.

Afferent Pathways↗

Preventive action of vitamin E-containing liposomes on cataractogenesis in young adult rats fed a 25% galactose diet.

The preventive action of vitamin E (Vit. E)-containing liposomes on cataractogenesis was examined in male Wistar rats (five weeks old) fed a 25% galactose diet. Vit. E-containing liposomes prepared with dipalmitoylphosphatidylcholine were instilled into both eyes three times a day over a 45-day period. Cataract appeared at 18-day galactose feeding and developed gradually thereafter. Simultaneous Vit. E-containing liposome instillation delayed this cataractogenesis. Lenses of 18-day galactose-fed rats showed decreases in Vit. E and reduced glutathione (GSH) contents and Na+, K(+)-ATPase activity and increases in lipid peroxide (LPO), galactitol, and water contents. Lenses of 45-day galactose fed rats showed decreases in GSH content and Na+,K(+)-ATPase activity and increases in Vit. E, LPO, galactitol, and water contents. Serum Vit. E and cholesterol levels decreased in 18-day galactose-fed rats, while both levels increased in 45-day galactose-fed rats. Simultaneous Vit. E-containing liposome instillation prevented these changes except for the changes of lenticular galactitol and water contents and serum Vit. E and cholesterol levels. These results indicate that simultaneously instilled Vit. E-containing liposomes can delay cataractogenesis in young adult rats fed a 25% galactose diet mainly by the antioxidative action of Vit. E contained in the instilled liposomes.

Animals↗

Calcitonin gene-related peptide inhibits proliferation and antigen presentation by human peripheral blood mononuclear cells: effects on B7, interleukin 10, and interleukin 12.

CGRP is a neuropeptide that has previously been described to possess immunosuppressive activities. CGRP is released from peripheral nerves that, in the skin, are in close physical association with dendritic APC. We sought to investigate the mechanisms by which CGRP can inhibit immune responses by studying its effects on human peripheral blood mononuclear cells (PBMC). Using allogeneic monocytes as stimulator cells, CGRP could inhibit the proliferation of PBMC by 47% when CGRP was present for the duration of culture. Interestingly, when the stimulator monocytes were incubated with CGRP for 2 h prior to irradiation then washed, the observed inhibition increased to 85%, suggesting that CGRP was exerting a direct effect on the monocyte stimulator population. Finally, the recall response to tetanus toxoid (TT) by PBMC from individuals vaccinated with TT 14 d prior was inhibited by 25-50% in the presence of CGRP. Also, CGRP decreased the levels of B7.2 but not B7.1 on treated monocytes, and this inhibition could be abrogated by the addition of anti-IL-10 antibody, suggesting that the inhibition was mediated by an increase in IL-10 production. Moreover, increased IL-10 production was confirmed by ELISA. Both IL-12 p40 and IFN-gamma levels in CGRP-treated cultures were found to be decreased by approximately 30%. The decrease in IL-12 p40 levels could be reversed by addition of anti-IL-10. These data suggest that CGRP inhibits PBMC proliferation, in part, through the release of IL-10, which in turn can downregulate important co-stimulatory molecules and the cytokines IL-12 and IFN-gamma.

Antigen Presentation↗

Expression of neurotrophic factors and neuropeptide receptors by Langerhans cells and the Langerhans cell-like cell line XS52: further support for a functional relationship between Langerhans cells and epidermal nerves.

Epidermal Langerhans cells are frequently anatomically associated with calcitonin gene-related peptide-containing nerves. Furthermore, calcitonin gene-related peptide inhibits Langerhans cells antigen-presenting function in several assays. Studies were performed to further explore the hypothesis that Langerhans cells and nerves have a functional relationship. To examine whether Langerhans cells may produce factors that influence nerve cell differentiation, we utilized the Langerhans cell-like cell line XS52 as a surrogate for Langerhans cells and compared it with Langerhans cells enriched to 90%. Supernatants conditioned by lipopolysaccharide-stimulated XS52 cells were able to induce the differentiation of the pheochromocytoma line PC12 into sympathetic neuron-like cells. This was also the case with enriched Langerhans cells stimulated by lipopolysaccharide. Pretreatment of conditioned supernatants with specific neutralizing anti-sera indicated that most of the differentiation-inducing activity was due to interleukin-6 and a small amount was due to nerve growth factor and basic fibroblast growth factor. By reverse transcriptase polymerase chain reaction, three clones of the XS52 cell line, XS52-4D, XS52-11D, and XS52-8B, were found to express mRNA for interleukin-6 and expression was markedly augmented by lipopolysaccharide. mRNA for nerve growth factor and basic fibroblast growth factor was detected in XS52-4D and XS52-11D, but not in XS52-8B. The expression of these neurotrophic factors by enriched Langerhans cells was quite similar to that of XS52-4D. In order to examine whether Langerhans cells may express receptors for nerve-derived peptides, reverse transcriptase polymerase chain reaction was employed to look for pituitary adenylate cyclase activating polypeptide type I, type II, and type III, and gastrin-releasing peptide receptors. All clones examined, as well as enriched Langerhans cells, expressed pituitary adenylate cyclase activating polypeptide type II and type III, and gastrin-releasing peptide receptors. These results suggest bi-directional signalling between Langerhans cells and nerves; nerve cells may regulate Langerhans cell function by elaboration of certain neuropeptides whereas Langerhans cells may promote the differentation of nerves by elaboration of interleukin-6 and, possibly, other factors.

Animals↗

Trichogenic trichoblastoma arising on the supraclavicular fossa with an immunohistochemical study of cytokeratin expression.

We report a 52-year-old female with trichogenic trichoblastoma arising on the supraclavicular fossa. Clinical and histological examinations revealed a thumbnail-sized, elastic, hard, subcutaneous nodule which consisted of keratinous cysts and epithelial cords of basaloid cells with focally follicular differentiation. Based on histological observations, a diagnosis of trichogenic trichoblastoma was made. An immunohistochemical study using a panel of monoclonal antibodies against cytokeratins was performed to investigate the nature and differentiation of this tumour. The most characteristic findings of the immunohistochemistry were CK 8 and 19 expression in the epithelial cords and the outer cells of the cystic structures. These immunoreactivities were similar to those of the outermost layer of the outer root sheath between the lower permanent portion and the upper transient portion, and immunostaining with the other antibodies confirmed this similarity. We can speculate that trichogenic trichoblastoma differentiates mainly toward the outermost layer of the outer root sheath between the lower permanent portion and the upper transient portion, and then into follicular structures.

Female↗

Trichoblastic fibroma. A case report and an immunohistochemical study of cytokeratin expression.

A 47-year-old woman noticed a nodule on her right shoulder that had been gradually increasing in size without symptoms. Histologic features of the biopsied nodule included round to irregularly shaped epithelial lobules demarcated by abundant sclerotic stroma located within the lower dermis and extending to the subcutis. The epithelial lobules consisted of cuboidal to columnar basaloid cells and were frequently arranged in narrow strands with many bifurcations and branching. Cystic structures containing lamellar keratinous material were occasionally found in connection with the lobules. The histologic findings were interpreted as trichoblastic fibroma. Immunohistochemical studies with antibodies directed against cytokeratins (CK) and involucrin revealed positive staining in most of the tumor cells with RCK102 and 34 beta E12 antikeratin antibodies, whereas the epithelial cords and the peripheral cells of the cystic structures stained with 170.2.14, 4.1.18, and CAM 5.2 antikeratin antibodies. However, CK1 or simple epithelial cytokeratins were not detected in any neoplastic elements. Based on comparative immunohistochemical findings in normal hair follicles, we propose that trichoblastic fibroma may first differentiate toward the outermost cell layer of the outer root sheath between the lower permanent portion and the upper transient portion and then into various other parts of the hair follicle.

Epithelium↗

Involvement of oxidative stress in D-xylose-induced cataractogenesis in cultured rat lenses.

In order to clarify the involvement of oxidative stress in in vitro sugar-induced cataractogenesis, we examined changes in lipid peroxide, reduced glutathione, vitamin E, and water contents following cataractogenesis in rat lenses cultured with 20 mM D-xylose over a period of 24 h. In D-xylose-treated lenses, an apparent opacity appeared at the equator after 6 h of D-xylose treatment, increases in lipid peroxide and water contents and decreases in reduced glutathione and vitamin E contents occurred with the appearance of opacity. We further examined the effect of the treatment of vitamin E in a liposomal form on cataractogenesis and the changes of lipid peroxide, reduced glutathione, vitamin E, water, and xylitol contents in rat lenses cultured with 20 mM D-xylose for 24 h. This vitamin E treatment significantly prevented not only cataractogenesis, but also an increase in lipid peroxide content and a decrease in vitamin E content in the D-xylose-treated lenses. However, the vitamin E treatment had no effect not only on a decrease in reduced glutathione content, but also on increases in water and xylitol contents, which are known to be induced via aldose reductase, in the D-xylose-treated lenses. These results indicate that not only osmotic stress but also oxidative stress should be involved in cataractogenesis in rat lenses cultured with D-xylose and support the involvement of oxidative stress in in vitro sugar-induced cataractogenesis.

Animals↗

So-called mixed tumor of the skin on the wrist: an immunohistochemical study.

A case of so-called mixed tumor of the skin arising on the wrist was reported. Immunohistochemical staining of keratins of several molecular weights (AE1/AE3, RCK102, NCL-5D3 and 35 beta H11), carcinoembryonic antigen (CEA), S-100 protein, and desmin was performed. AE1/AE3 and RCK102 were positive in all the tumor cells; CEA, NCL-5D3 and 35 beta H11 were positive mainly in luminal cells of the tubuloalveolar structures. S-100 protein was positive in peripheral cells of the tubular lumina and in scattered cells in the mucous stroma. Desmin was negative in all the tumor cells. Immunohistochemical findings lent further support to the hypothesis that so-called mixed tumor of the skin differentiates into the secretory and ductal portions of the sweat gland.

Adenoma, Pleomorphic↗

Osteoarthritis in 84 Japanese patients with palmoplantar pustulosis.

BACKGROUND: Palmoplantar pustulosis (PPP) is often associated with osteoarthritis. The relation between osteoarthritis in PPP and other types of seronegative arthritis remains unclear. OBJECTIVE: The purpose of this study was to investigate the distribution and the frequency of osteoarthritis in patients with PPP and to compare HLA antigen frequencies in osteoarthritis in PPP, psoriatic arthritis, and ankylosing spondylitis. METHODS: Clinical findings were identified and HLA-A, -B, -C, and -DR were determined in 84 Japanese patients with PPP. Bone scintigraphic studies were conducted for forty-one patients. RESULTS: In addition to the anterior aspect of the chest wall, the knee, spine, and ankle were frequently involved. HLA-DR9 frequency was the highest in patients with PPP who had osteoarthritis. CONCLUSION: Involvement of the knees, spine, ankles, and the anterior aspect of the chest wall was noted in patients with osteoarthritis and PPP. Osteoarthritis in PPP seems to be a distinct entity from a genetic point of view.

Adult↗

Interferon-alpha (INF-alpha) and etretinate in the treatment of mycosis fungoides.

A combination therapy of mycosis fungoides (MF) with interferon-alpha (INF-alpha) and etretinate was reported. A 53-year-old patient suffering from MF was treated with intramuscular administration of INF-alpha at a dosage of 9 x 10(6) IU daily; skin lesions poorly responded to the treatment. After oral etretinate with a dosage of 50 mg daily was combined with INF-alpha, marked clinical improvement was seen in skin lesions with minor side effects. INF-alpha in combination with etretinate can have beneficial effects in the treatment of MF.

Administration, Oral↗