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Biomedical subjects

F Kaneko

Publications and source records attributed to F Kaneko.

At least 37 records · Page 2Linked to original sources
PubMed2000

Up-regulation of E-cadherin and I-catenin in human hepatocellular carcinoma cell lines by sodium butyrate and interferon-alpha.

Human E-cadherin is a homophilic cell adhesion molecule and its expression is well preserved in normal human hepatocytes; a decrease in its expression has been observed in poorly differentiated hepatocellular carcinoma cells. We examined the alteration of E-cadherin and catenin expressions caused by differentiation inducers in human hepatocellular carcinoma cells. Hepatocellular carcinoma cell lines, HCC-T and HCC-M, were cultured with all-trans retinoic acid (ATRA), dexamethasone (DEX), sodium butyrate, and interferon-alpha. E-cadherin expression was only up-regulated by butyrate and interferon-alpha (IFN-alpha) in both cell lines, studied by means of fluorescence immunostaining and flow cytometry. The localization of E-cadherin staining was shown at their cell membrane. According to the increase in E-cadherin expression, beta-catenin expression appeared at the cell membrane of both cell lines when treated with butyrate and IFN-alpha. Such an appearance was not observed when cells were treated with ATRA and DEX. Western blotting showed that alpha- and y-catenin expression was not changed, while only the expression of beta-catenin increased. Beta-catenin oncogenic activation as a result of amino acid substitutions or interstitial deletions within or including parts of exon 3, which has been demonstrated recently, was not detected in these cell lines by direct deoxyribonucleic acid sequencing. These results suggest that the expression and interaction between E-cadherin and wild-type beta-catenin are potentially modulated by butyrate and IFN-alpha, and that these two agents are potent inhibitors of hepatocellular carcinoma cell invasion and metastasis.

Amino Acid Substitution↗
PubMed2000

[Acute eosinophilic pneumonia induced by cigarette smoking].

The subject was a 24-year-old man who presented with acute fever, dry cough, and dyspnea. Chest X-ray films revealed diffuse infiltrates in both lungs. Bronchoalveolar lavage fluid specimens contained an increased number of eosinophils. Transbronchial lung biopsy specimens demonstrated the infiltration of eosinophils into alveolar walls and air spaces. These findings were consistent with acute eosinophilic pneumonia. The patient recovered without medical treatment. Eight days prior to admission, he had resumed smoking after 3 years of abstention. It was suggested that the cause of acute eosinophilic pneumonia in this case was associated with the resumption of smoking. To confirm that association, a smoking challenge test is usually necessary. However, similar symptoms also developed later, after the patient was passively exposed to cigarette smoke. Therefore, we concluded that smoking was probably the etiologic agent of his illness.

Acute Disease↗
PubMed2000

The main factor causing prolonged reaction time on force producing process following anterior cruciate ligament reconstruction.

This study investigated the electromechanical properties of atrophied human quadriceps femoris muscle during a voluntarily elicited maximal isometric contraction (MVC) and a peripherally stimulated twitch contraction. Nineteen patients were recruited 2-3 months following a unilateral anterior cruciate ligament (ACL) reconstruction. Both the involved leg as well as the uninvolved leg were studied. Maximal twitch response was elicited and surface electromyograms (EMG) were recorded from the vastus lateralis. Total reaction time (TRT) for both MVC and twitch on involved leg was prolonged (251.47 msec, 26.01 msec). This prolongation suggests an extended lag in avoiding injury such as during sports. Pre-motor time during both MVC and twitch (PMTmvc, PMTtwitch) did not differ between both groups. Electromechanical delay during MVC (EMDmvc) was prolonged on involved leg (53.42 msec), and also evoked twitch EMD (EMDtwitch) (20.04 msec) as compared to the opposite side. Prolonged EMDtwitch may be due to a decrease in stiffness of the series elastic component, changes of peripheral muscle composition to containing more slow type muscle fibers, or a decrease in function of the excitation-contraction (E-C) coupling process. A prolonged EMDtwitch can also explain the prolonged EMDmvc. These findings also suggested that prolonged TRTmvc to visual stimulus during MVC in atrophied human quadriceps femoris muscle after disuse was principally due to prolongation of EMDmvc. Prolonged EMDmvc may have resulted from decreased muscle stiffness, which was evident in the prolongation of the EMDtwitch.

Anterior Cruciate Ligament↗
PubMed1999

Overexpression of monocyte-derived cytokines in active psoriasis: a relation to coexistent arthropathy.

An overexpression of inflammatory cytokines has been found in the lesional skin as well as peripheral blood in patients with psoriasis, although its etiological significance is not yet understood. In order to evaluate the cell type responsible for the elevated cytokines in the peripheral blood, we investigated cytokine profiles of the fractionated peripheral blood mononuclear cells (PBMCs) in 30 patients with psoriasis and 27 healthy controls. Without stimulation, higher levels of interleukin (IL)-1beta, IL-6, and IL-8 were produced by freshly isolated PBMCs from the patients than those from the controls. In the fractionated PBMCs, the monocyte-rich fractions were mainly responsible for the production of these cytokines and mRNA. The elevated levels of monocyte-derived cytokine mRNAs decreased following successful treatment with cyclosporin A. Although no correlation was found between the cytokine levels and the psoriasis area and severity index (PASI) scores, patients with arthropathy showed significantly high production levels of IL-1beta, IL-6, and IL-8. These findings suggest that monocytes are the major cell source producing inflammatory cytokines in the peripheral blood of psoriasis, and the increased cytokine levels are related to the coexistent arthropathy rather than the severity of cutaneous lesions.

Adult↗
PubMed1999

Internalization of constitutive desmogleins with the subsequent induction of desmoglein 2 in pemphigus lesions.

Acantholytic blisters in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are caused by a dissociation of desmosomes mediated by autoantibodies against desmoglein (Dsg) 3 and Dsg 1, respectively. The blistering occurs at the suprabasilar level in PV and at the subcorneal level in PF, which corresponds to the distribution of target antigens in the epidermis: there is a more prominent expression of Dsg 1 in the upper layer, whereas Dsg 3 is more prominent in the lower layer. To elucidate the histogenesis of acantholysis, we studied the alterations of the desmosomal components and the expression pattern of Dsg isoforms in the lesional and perilesional epidermis of pemphigus patients. The results demonstrated an internalization of the desmosomes in the lower epidermis of PV, PF and pemphigus vegetans. A similar phenomenon was induced in monolayers of keratinocytes cultured with PV sera. However, little change was observed in E-cadherin expression until acantholysis became manifest. This internalization occurred prior to overt acantholysis, and was frequently associated with the induction of Dsg 2 expression in the basilar or lower layers of the epidermis. These findings indicate an alteration of Dsg isoform expression in subclinical pemphigus lesions, which might be related to the characteristic acantholytic patterns: the suprabasilar layer in PV and the upper epidermis in PF.

Cells, Cultured↗
PubMed1999

The association of latent Epstein-Barr virus infection with hydroa vacciniforme.

Patients with hydroa vacciniforme (HV)-like eruptions and malignant potential have been reported from Asia and Mexico, and those patients frequently had an associated latent Epstein-Barr virus (EBV) infection. In order to elucidate the association of latent EBV infection with HV, we studied six children with typical manifestations of HV by detection of EBV genes and EBV-related RNAs in biopsy specimens from cutaneous lesions. Cutaneous lesions of all six children with typical HV contained EBV-encoded small nuclear RNA (EBER)+ cells in 3-10% of the dermal infiltrates, whereas no Bam HI-H, l-fragment (BHLF) mRNA, or transcripts encoding EA-D antigen, were detected. No EBER + cells were detected in other inflammatory or benign lymphoproliferative skin disorders tested. Polymerase chain reaction amplification confirmed the presence of EBV DNA sequences in five of six biopsy specimens from the patients. Latent EBV infection is associated with the development of cutaneous lesions of HV.

Burkitt Lymphoma↗
PubMed1999

Expression of sonic hedgehog signal transducers, patched and smoothened, in human basal cell carcinoma.

In basal cell nevus syndrome (BCNS) patients, mutations of a gene, patched (ptc), which encodes a putative signal transducer of sonic hedgehog protein (SHH), were found and are thought to be one of the major causes of BCNS. The SHH signaling pathway is an important developmental pathway, and ptc protein (PTC) is a suppressive component serving as a receptor for the secreted SHH. Another transmembrane protein, smoothened (SMO), forms a complex with PTC and regulates this signaling pathway. Recent transgenic studies have strengthened the importance of the SHH signaling system in the etiology of basal cell carcinoma (BCC). In this study, we examined the expression patterns of mRNA for ptc and smo in two different BCC subtypes and normal skin. We found that the expressions of ptc and smo mRNA were enhanced in the tumor nests of the nodular BCC, especially at the advancing portions, but were under the detectable level in the superficial BCC cases examined, indicating that ptc and smo mRNA expressions might be associated with BCC tumor progression and divide the BCC histologic types into two subtypes, superficial and nodular types. In addition, no obvious signals for ptc and smo mRNA were detected in the normal human epidermis, appendages, or seborrheic keratosis, indicating that the abnormal proliferation of follicular epithelial cells caused by ptc, smo and/or other genetic changes, which also cause ptc and smo overexpressions, might result in BCC tumor formation.

Aged↗
PubMed1999

Induction of transcription factor AP-2 by inflammatory cytokines in human keratinocytes.

Activator protein-2 is an important transcription factor for the activation of a number of genes. Here we report the induction of activator protein-2 in response to inflammatory cytokines such as interleukin-6 in keratinocytes. Immunoblotting and semiquantitative reverse transcriptase-polymerase chain reaction assays using normal human keratinocytes revealed that interleukin-6 caused a time- and concentration-dependent induction of activator protein-2 mRNA and protein. The increase of activator protein-2 mRNA was detected at 30 min after stimulation and that of activator protein-2 protein was at 2 h. Their levels were lower than the control levels at 24 h. The interleukin-6-dependent induction of activator protein-2 mRNA was completely blocked by adding actinomycin D, whereas it was approximately 50% affected by cycloheximide. Co-incubation with neutralizing antibodies against various inflammatory cytokines resulted in inhibition of the interleukin-6-dependent activator protein-2 induction at varying degrees, indicating an involvement of various cytokines in the activator protein-2 induction. The activator protein-2 induction was observed in keratinocytes derived from lesional skins with psoriasis or squamous cell carcinoma, and the high levels of activator protein-2 were histochemically detected in these lesions. Furthermore, a gel mobility shift assay using the nuclear extracts from interleukin-6-treated cells showed that interleukin-6 induced the functional activator protein-2 protein for the gene activation. These findings suggest a possible regulation mechanism of activator protein-2 through a complex cytokine system, which is conceivably the initial reaction leading to skin inflammation, and resultant keratinocyte growth and carcinogenesis.

Aged↗
PubMed1999

Interleukin-15 is not a constitutive cytokine in the epidermis, but is inducible in culture or inflammatory conditions.

The regulation in the skin of interleukin-15 (IL-15), a potent modulator of T-cell-mediated immune responses, is not fully understood. We investigated the levels of IL-15 and its mRNA produced by epidermal and cultured keratinocytes and found that normal keratinocytes did not constitutively express IL-15 in the epidermis, but in culture began to produce the cytokine. Some epidermal keratinocytes expressed IL-15 in inflammatory conditions associated with infiltration of neutrophils and eosinophils. IL-15 was detected only in the cell lysates, not in the supernatants of cultured keratinocytes. Dexamethasone (10(-5)-10(-6) M) markedly inhibited IL-15 mRNA expression by normal and transformed keratinocytes in a range of pharmacological concentrations. IFN-gamma (200 and 400 U/ml) slightly increased the IL-15 message level in a squamous cell carcinoma cell line, HSC-5, in a dose-dependent fashion, whereas no significant change was observed in cultured normal human keratinocytes. Our data indicate that IL-15 is not a constitutive cytokine in epidermal keratinocytes but is inducible.

Antineoplastic Agents↗
PubMed1999

Structural analyses of polymorphic transitions of sn-1, 3-distearoyl-2-oleoylglycerol (SOS) and sn-1, 3-dioleoyl-2-stearoylglycerol (OSO): assessment on steric hindrance of unsaturated and saturated acyl chain interactions.

Polymorphic transformations in two saturated-unsaturated mixed acid triacylglycerols, SOS (sn -1,3-distearoyl-2-oleoylglycerol) and OSO (sn -1,3-dioleoyl-2-stearoylglycerol), have been studied by FT-IR spectroscopy using deuterated specimens in which stearoyl chains are fully deuterated. A reversible phase transition between sub alpha and alpha and a series of irreversible transitions (alpha-->gamma-->beta'-->beta (beta2, beta1) for SOS and alpha-->beta'-->beta for OSO) were studied with an emphasis on the conformational ordering process of stearoyl and oleoyl chains. The alpha-->sub alpha reversible transition was due to the orientational change of stearoyl chains in the lateral directions from the hexagonal subcell to a perpendicularly packed one. As the first stage of the series of irreversible transitions from alpha to beta, the conformational ordering of saturated chains took place in the alpha-->gamma transition of SOS and in the alpha-->beta' transition of OSO; one stearoyl chain in SOS and OSO takes the all-trans conformation and the second stearoyl chain in SOS takes the bent conformation like those observed in the most stable beta-type. As the final stage, the ordering of unsaturated chains occurred in the beta'-->beta transition both for SOS and OSO. A conversion in the layered structure from bilayer to trilayer was also accompanied by the conformational ordering in the alpha-->gamma transition of SOS and in the beta'-->beta transition of OSO.

Allosteric Site↗
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

Diversity in the fatty-acid conformation and chain packing of cis-unsaturated lipids.

Recent X-ray diffraction and Fourier transform IR spectroscopic studies have unveiled a great diversity in the molecular conformation and chain packing of lipid molecules containing cis-unsaturated fatty-acid chains. Specifically, a dramatic diversity in the olefinic conformation, subcell packing and chain-chain interactions has been clearly revealed by crystal structures of principal cis-monounsaturated fatty acids. The structural diversity is most manifest in oleic acid crystals. These findings were applied to analyses of the complicated structural transformation of diacylglycerols and triacylglycerols containing oleic acid and saturated acid moieties, in which the stabilization of the oleic acid causes the complexity of the transformation and mixing behavior. Although this knowledge has been obtained in the crystalline state, one may assume that the structural diversity of these unsaturated molecules plays a similar role in the lipids of biomembranes, lipoproteins and lipid deposits in which aliphatic chain packing is a critical problem, since most lipid domains can undergo liquid to solid or solid to liquid alterations.

Crystallization↗
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↗