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Biomedical subjects

F Kaneko

Publications and source records attributed to F Kaneko.

At least 19 recordsLinked to original sources
PubMed1998

Nitric oxide synthesis in the lung. Regulation by oxygen through a kinetic mechanism.

In this study, we show that oxygen regulates nitric oxide (NO) levels through effects on NO synthase (NOS) enzyme kinetics. Initially, NO synthesis in the static lung was measured in bronchiolar gases during an expiratory breath-hold in normal individuals. NO accumulated exponentially to a plateau, indicating balance between NO production and consumption in the lung. Detection of NO2-, NO3-, and S-nitrosothiols in lung epithelial lining fluids confirmed NO consumption by chemical reactions in the lung. Interestingly, alveolar gas NO (estimated from bronchiolar gases at end-expiration) was near zero, suggesting NO in exhaled gases is not derived from circulatory/systemic sources. Dynamic NO levels during tidal breathing in different airway regions (mouth, trachea, bronchus, and bronchiole) were similar. However, in individuals breathing varying levels of inspired oxygen, dynamic NO levels were notably dependent on O2 concentration in the hypoxic range (KmO2 190 microM). Purified NOS type II enzyme activity in vitro was similarly dependent on molecular oxygen levels (KmO2 135 microM), revealing a means by which oxygen concentration affects NO levels in vivo. Based upon these results, we propose that NOS II is a mediator of the vascular response to oxygen in the lung, because its KmO2 allows generation of NO in proportion to the inspired oxygen concentration throughout the physiologic range.

Adult↗
PubMed1998

Loss of butyrate-induced apoptosis in human hepatoma cell lines HCC-M and HCC-T having substantial Bcl-2 expression.

We have demonstrated that sodium butyrate induces differentiation in human hepatoma cells; however, recent studies have shown that this agent causes apoptosis in some types of cancer cells. In this study, we examined whether sodium butyrate causes apoptosis in the human hepatoma cell lines, HCC-M and HCC-T. The growth of human hepatoma cells was dose-dependently reduced by sodium butyrate. Flow cytometric analysis showed cell-cycle arrest at the G1 phase in the sodium butyrate-treated cells. Apoptotic change was never found in treated cells at concentration levels of less than 5 mmol/L. Sodium butyrate decreased p53 expression and increased p21WAF-1 expression in HCC-T and HCC-M cells having the wild-type p53 gene. Western blot analysis showed that Bcl-2 was expressed in the HCC-T and HCC-M cells, and its expression was increased after exposure to sodium butyrate. Antisense oligodeoxynucleotide against bcl-2 easily caused apoptosis. These results indicate that sodium butyrate hardly induces apoptotic change in the human hepatoma cell lines, HCC-T and HCC-M, with the increase of Bcl-2 expression. Cell-cycle arrest in the G1 phase caused by sodium butyrate was suggested to be induced by the increase in p21WAF-1 expression, but this change did not link with the p53 increase.

Apoptosis↗
PubMed1998

Different growth properties in response to epidermal growth factor and interleukin-6 of primary keratinocytes derived from normal and psoriatic lesional skin.

Epidermal growth factor (EGF) family members and its receptor (EGFR) are thought to have an important role in the proliferation of epidermal keratinocytes. In this report, we investigated the EGF/EGFR system in primary keratinocytes derived from normal and psoriatic lesional skin. EGF elicited the growth of both normal human keratinocytes (NHKs) and psoriatic lesional keratinocytes (PLKs). Interleukin-6 (IL-6) potentiated the EGF-dependent growth of NHKs, but has no observable effect on PLKs, while IL-6 itself showed no growth-stimulating activities in both cell types. Immunodetection and in situ hybridization analyses revealed that IL-6 induces EGFR expression in NHKs in a time- and dose-dependent manner. This EGFR expression decreased reversibly to an undetectable level when IL-6-treated NHKs were re-cultured in IL-6-free conditions. On the other hand, PLKs expressed high levels of EGFR even when unstimulated and the expression level was not affected by IL-6 stimulation. These results suggest that the EGF/EGFR system is involved in the growth of NHKs and PLKs and that IL-6 potentiates NHK growth partly through the induction of EGFR. The different EGFR regulatory system may contribute to the pathogenesis of psoriasis.

Adult↗
PubMed1998

Suplatast tosilate (IPD), a new immunoregulator, is effective in vitiligo treatment.

The major type of vitiligo is considered to be an autoimmune disorder. Anti-melanocyte antibodies are frequently detected in sera of patients with this disease. Interleukin (IL)-4 released from Th2 cells is an important factor in stimulating autoantibody production by B-cells. In this study, seven patients with vitiligo treated with suplatast tosilate (IPD), three showed repigmentation and improvement of their lesions after administration of the drug. IPD halted the continuous spread of the lesions in three of the other patients, and, in two of them, also reduced microsome test and thyroid test titers. The efficacy of IPD in treating vitiligo was thought to be due to the suppressive effect of this drug on IL-4 production. No side effect was observed. Thus IPD may represent a new alternative in vitiligo treatment due to its inhibition of autoimmunity by the suppression of IL-4.

Administration, Oral↗
PubMed1997

Role of transforming growth factor-beta 1 in fibroblasts derived from normal and hypertrophic scarred skin.

In order to elucidate the effect of transforming growth factor beta 1 (TGF-beta 1) on normal dermal fibroblasts (NDF) and on fibroblasts derived from hypertrophic scar (HSF) tissue, we compared proliferation, the levels of TGF-beta 1 protein and mRNA, the activity of type-I collagen synthesis and collagenase, and the response to recombinant human (rh) TGF-beta 1 in cultures of both types of cells which had been simultaneously collected from the same patients. We also studied the effects of anti-TGF-beta 1 antibody on the proliferation of these two types of fibroblasts in culture. In spite of the fact that the growth rate of HSF was higher than that of NDF, NDF proliferation was more sensitive to the concentration of rhTGF-beta 1. With respect to rates of synthesis, the results obtained in both groups revealed that the production of type-I collagen was higher and collagenase activity was lower in culture supernatants of HSF. However, the addition of rhTGF-beta 1 resulted in a decrease in the collagenase/collagen ratio in NDF, but failed to induce any change in this ratio in HSF. In addition, the production of TGF-beta 1 and the expression of TGF-beta 1 mRNA in HSF were greater than in NDF. Furthermore, anti-TGF-beta 1 antibody reduced the rate of growth of HSF. These results suggest that HSF are able to produce TGF-beta 1, resulting in enhanced proliferation of these cells as well as in a rapid synthesis of type-I collagen through an autocrine mechanism which may lead to hypertrophic scarring.

Adult↗
PubMed1997

Effects of prostaglandin E1 on cultured dermal fibroblasts from normal and hypertrophic scarred skin.

To investigate the role of prostaglandin (PG) E1 in preventing scar formation as well as that of the related cytokines, we culture fibroblasts from hypertrophic scar tissue (SDF) and normal dermis (NDF) collected from patients with scar contracture. We have compared the type I collagen synthesis, type I collagenase activity, and the production of interleukin (IL)-6, IL-8 and transforming growth factor (TGF)-beta(1) in two types of cultured fibroblasts before and after addition of PGE1. Our results demonstrated that levels of type I collagen and TGF-beta(1) production were higher and that type I collagenase activity and IL-8 production were significantly lower in the culture supernatants of SDF. There was no significance difference in IL-6 production between SDF and NDF culture supernatants. On the other hand, PGE1 significantly increased type I collagenase activity and IL-8 production in the SDF culture supernatants and it increased IL-6 and TGF-beta(1) production in both types of fibroblasts. However, there was no effect on synthesis of type I collagen in either group. To further investigate the role of TGF-beta(1) in NDF and SDF, exogenous recombinant human (rh) TGF-beta(1) was added. In NDF group, rhTGF-beta(1) induced a decrease in the type I collagenase/type I collagen ratio, while rhTGF-beta(1) had no effect on the same ratio in the SDF group. These results suggest that PGE1 may have a role in the prevention of hypertrophic scar by increasing the activity of type I collagenase.

Adolescent↗
PubMed1997

The mode of action of prostaglandin (PG) I1 analog, SM-10906, on fibroblasts of hypertrophic scars is similar to PGE1 in its potential role of preventing scar formation.

The effects of prostaglandin (PG) I1 analog, SM-10906 (SM-6) and PGE1 on extracellular matrix formation and the release of cytokines by cultured normal human dermal fibroblasts (NDF) and hypertrophic scar fibroblasts (HSF) were compared in order to evaluate the clinical efficacy of PGs in preventing scar formation. In the present study, we measured type I collagen synthesis, collagenase activity, production of interleukin (IL)-6, IL-8, and transforming growth factor (TGF)-beta 1 and levels of adenosine 3,5-cyclic monophosphate (cAMP) in NDF and HSF cultured with or without PGs. The results demonstrated that HSF culture supernatants has a significantly higher level of type I collagen and TGF-beta 1 than those of NDF. However, the levels of collagenase activity and IL-8 in HSF were significantly lower in comparison to that of NDF. There was no substantial difference in IL-6 production between two types of culture cells. On the other hand, PGE1 and SM-6 significantly enhanced collagenase activity and raised the collagenase/type I collagen ratio in the HSF supernatants. In addition, both PGE1 and SM-6 increased production of TGF-beta 1, IL-8 and IL-6 and levels of cAMP in both cell types. However, they had no effect on the type I collagen synthesis of either types. These results suggest that, the stable PGI1 analog, SM-6, similarly acts as PGE1 in HSF by increasing the activity of collagenase.

Adolescent↗
PubMed1997

Streptococcal infection in the pathogenesis of Behçet's disease and clinical effects of minocycline on the disease symptoms.

Although the precise pathoetiology of Behçet's disease (BD) remains obscure, patients with BD have a high incidence of chronic infectious foci, indicating an enhanced susceptibility to chronic tonsillitis, and dental caries. Sometimes, clinical symptoms appear after treatment of these foci in BD patients. It is believed that BD might be related to an allergic reaction to a bacterial infection in view of the many clinical symptoms, especially the presence of aphthous and genital ulcerations. An attempt to obtain cutaneous responses to bacterial antigens has been carried out using various vaccines developed from bacteria isolated from the ulcerative lesions and oral cavities of BD patients. BD patients often show intense hypersensitivity to various strains of streptococci, not only by their cutaneous reactions but also by in vitro testing. In this report, we describe our previous studies on the correlation between streptococcal antigens and the pathogenesis of BD and also discuss the recent reports of other authors. The intense hypersensitivity to streptococcal antigens acquired after streptococcal infection is thought to play an important role in the appearance of symptoms in BD patients since the production of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMC) was enhanced when stimulated with streptococcal antigen in a culture system. Minocycline, an antibiotic to which certain strains of streptococci are sensitive, reduced the frequency of clinical symptoms in BD patients as well as the production of pro-inflammatory cytokines by BD-PBMC stimulated with streptococcal antigen.

Adult↗
PubMed1997

[The correlation between interleukin-10 and interferon-gamma produced by peripheral blood mononuclear cells stimulated by house dust mite antigen in atopic dermatitis].

The production of interleukin (IL)-10 and interferon (IFN)-gamma by peripheral blood mononuclear cells (PBMC) stimulated by house dust mite (HDM)antigen and concanavaln A (Con A) was measured in patients with atopic dermatitis (AD). The HDM-stimulated PBMC from AD patients revealed to produce significantly higher levels of IL-10 (12 h: 918.4 +/- 206.5, 24 h: 1252.5 +/- 145.8, 72 h: 1332.7 +/- 123.9 pg/ml) than those from normal control subjects (12 h: 231.1 +/- 139.0, 24 h: 585.7 +/- 196.2, 72 h: 813.5 +/- 181.8 pg/ml). Con A-stimulated AD-PBMC also showed significantly higher levels of IL-10 production than those from normal controls, although they were lower than the productions induced by HDM antigen. By contrast, the levels of IFN-gamma from AD PBMC stimulated with HDM or Con A, were significantly lower than those from normal controls. IFN-gamm production might be down-regulated by IL-10 in AD-PBMC. The overproduction of IL-10 seems to show that helper T type 2 (Th2) cells are rather dominantly activated than Th1 cells and Th2 cells might contribute to produce the cytokines in response to HDM antigen in AD patients.

Adult↗
PubMed1997

Clinicopathologic manifestations of Epstein-Barr virus-associated cutaneous lymphoproliferative disorders.

OBJECTIVE: To elucidate clinicopathologic manifestations of cutaneous lymphoproliferative disorders associated with Epstein-Barr virus (EBV) infection. DESIGN: Retrospective survey of case series. SETTING: University hospital medical center. PATIENTS: Sixty-five patients with cutaneous lymphomas and related disorders. MAIN OUTCOME MEASURES: Detection of EBV genes and EBV-encoded small nuclear RNAs. RESULTS: Evidence of latent EBV infection was demonstrated in 15 patients: 3 had malignant lymphoma with clinical features mimicking cytophagic histiocytic panniculitis, 6 had facial vesiculopapular eruptions mimicking hydroa vacciniforme, 4 had angiocentric lymphoma, 1 had histiocytoid lymphoma associated with hemophagocytosis, and 1 had plasmacytoma. Hypersensitivity to mosquito bites was noted in a patient with hydroa vacciniforme-like eruptions and another with histiocytoid lymphoma. Angiocentric infiltration of atypical lymphoid cells was a common histological feature in the patients with hydroa vacciniforme-like eruptions and angiocentric lymphoma. No evidence of EBV infection was apparent in 19 patients with mycosis fungoides or Sézary syndrome, 7 with adult T-cell leukemia or lymphoma, 3 with lymphomatoid papulosis (type A), and 2 with lymphocytoma cutis. CONCLUSION: Patients with EBV-associated cutaneous lymphoproliferative disorders present with unique and diagnostic clinicopathologic features distinct from those of mycosis fungoides or Sézary syndrome.

Adolescent↗
PubMed1996

Pharmacokinetics and polymorphic oxidation of dextromethorphan in a Japanese population.

The plasma concentration and cumulative urinary excretion over 34 h of dextromethorphan, free and conjugated dextrorphan, and 3-hydroxymorphinan were determined in seven healthy Japanese subjects after oral administration of 30 mg dextromethorphan hydrobromide. Conjugated metabolites were extensively present, whereas no detectable dextromethorphan or free metabolites were observed in the plasma of any subject. On average, 72% of the dose was excreted in urine within 34 h. This was detected mainly as conjugated metabolites with only slight traces of dextromethorphan and free metabolites. From the time-courses of the metabolic ratio (the ratio of urinary output of dextromethorphan to dextrorphan), the metabolic ratios seemed to become constant 7.5 h after oral administration. Phenotyping was performed using metabolic ratios in 75 unrelated healthy Japanese subjects (43 males and 32 females). The logarithmic metabolic ratio was bimodally distributed and one subject (1.3%) was identified as a poor metabolizer.

Administration, Oral↗
PubMed1996

Clinical effectiveness of an ointment containing prostaglandin E1 for the treatment of burn wounds.

This report discusses the effectiveness of conservative treatment of burns using applications of prostaglandin E1 (PGE1) containing ointment (PGE1 ointment) to the wound site. Fourteen patients with superficial dermal burns (SDB), deep dermal burns (DDB) and full-thickness dermal burns (DB), who were treated with repeated applications of this ointment, showed rapid epithelialization of the affected tissue. Hypertrophic scarring after epithelialization was less than that expected after other therapies. The degree of scarring was graded as 'none', 'mild', 'moderate' or 'severe'. The results of this therapy revealed no scarring in two sites (8.7 per cent), mild scarring in 16 sites (69.6 per cent), moderate scarring in one site (4.3 per cent) and severe scarring in four sites (17.4 per cent) out of 23 sites distributed among the patients. The application of PGE1 ointment in combination with skin grafting surgery was found to improve functional and aesthetic results in the patients with DDB and DB, by minimizing the area of the donor site; it was especially useful for children with extensive burns because of the shortage of available tissue as donor site material for skin grafting.

Administration, Topical↗
PubMed1996

Secretory component (polymeric immunoglobulin receptor) expression on human keratinocytes by stimulation with interferon-gamma and differences in response.

Secretory IgA (sIgA) is a major protective factor in the mucosal immune system because of its great ability to form complexes with bacteria. Secretory component (SC) is an 80-kDa glycoprotein, a component of sIgA, which functions as a polymeric immunoglobulin receptor for IgA and aids the secretion of sIgA from the epithelial surface. We studied SC production by keratinocytes which were involved in the inflammatory process using interferon-gamma (IFN-gamma) as one of the major inflammatory promoters produced by helper T cells. Using two human squamous cell carcinoma cell lines (HSCs) and normal human keratinocytes (NHKs), results from flow cytometric analysis, enzyme-linked immunosorbent assay (ELISA), and Northern blotting revealed that HSCs produced SC when stimulated with IFN-gamma, although their responses differed; one line exhibited enhanced SC production whereas the production in the other line was suppressed. NHKs also exhibited SC expression on the cell surface by means of immunocytochemical analysis, flow cytometry and ELISA, however the responses were also different in each strain. Although the reason for the diversity of SC expression on keratinocytes is not clear, these differences may influence epidermal sIgA secretion level.

Base Sequence↗
PubMed1996

Abnormal desmoglein expression by squamous cell carcinoma cells.

Abnormal expression of cell adhesion molecules and related proteins has been observed in various carcinoma cells. We compared expression patterns of desmosomal cadherins, E-cadherin, and cytoplasmic plaque proteins of four different human squamous cell carcinoma cell lines and in vivo squamous cell carcinoma cells with those of normal human keratinocytes. Unlike normal human keratinocytes, the squamous cell carcinoma cells, both in culture and in vivo, exhibited diminished or unusual expression of desmoglein 3 and desmoglein 1, which bear pemphigus vulgaris and pemphigus foliaceus antigens, respectively. Abnormal expression of E-cadherin and cytoplasmic plaque proteins such as desmoplakin and plakoglobin was also observed. Western blotting study demonstrated that three squamous cell carcinoma cell lines expressed two desmogleins with a predominant 150 kDa molecule, and a minor 130 kDa one. Although these molecular sizes were similar to those of cultured normal human keratinocytes, the 130 kDa desmoglein, which usually carries pemphigus antigenic epitopes, was weakly or negatively reactive with pemphigus vulgaris serum. One squamous cell carcinoma cell line showed a doublet of 140 and 145 kDa bands in addition to the 130 kDa band. All the carcinoma cell lines constantly expressed desmoglein 2 and desmoglein 3 mRNA, whereas cultured normal human keratinocytes always expressed desmoglein 1 and desmoglein 3 mRNA, with or without desmoglein 2 mRNA. These findings indicate that the squamous cell carcinoma cells revealed abnormal expression of desmoglein isoforms, which may be related to tumor cell kinetics such as cell invasion and metastasis.

Antigens↗