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Biomedical subjects

F Kaneko

Publications and source records attributed to F Kaneko.

At least 73 records · Page 4Linked to original sources

Studies on cytokines related to wound healing in donor site wound fluid.

This study was performed to evaluate cytokines in donor-site wound fluids and to determine their effect on wound healing. A film dressing was applied to the donor-site wound of 24 patients immediately after a split-thickness skin graft was taken. On the 5th day after treatment, 2-3 ml of the fluid retained under the film dressing was collected by means of puncture with a syringe. Growth factors and cytokines considered to accelerate wound healing were present in relatively large amounts in the exudate. Very low concentrations of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were detected by a commercially-available enzyme-linked immunosorbant assay (ELISA) kit. However, the presence of both growth factors in wound fluid could not be confirmed because of the possible cross-reactivity of the antibodies to other EGF and FGF family growth factors. In contrast, platelet derived growth factor (PDGF), interleukin-6 (IL-6), transforming growth factor-alpha (TGF-alpha) and TGF-beta were present in relatively large amounts. The finding that certain cytokines coexist in a balanced state under the film dressing suggests that epithelization can proceed, since an adequate balance would insure proper regulation by the cytokine network. Our present study increases the likelihood that film or hydrocolloid dressings will be used more frequently in the future for treatment of burn wounds, ulcers or donor-site wounds since these dressings were shown to be more capable than ointments of retaining cytokines, particularly intrinsic growth factors secreted at the wound site.

Adult↗

Efficacy of hydroxyapatite ceramic as a carrier for recombinant human bone morphogenetic protein.

In this study, we investigated the efficacy of hydroxyapatite ceramic (HAP) as a carrier of bone morphogenetic protein (BMP) using porous HAP pellets artificially fabricated from limestone. After treatment with recombinant human BMP-2, the pellets were inserted beneath the cranial periosteum of rabbits, and the degree of osteogenesis was examined histologically. The degree of osteogenesis was also evaluated using image-analyzing procedures. Results showed that extensive bone formation had occurred around the pellets 3 weeks after insertion in the group that received pellets treated with recombinant human BMP alone as well as in the group that received recombinant human BMP in addition to type I collagen-treated HAP pellets. Subsequently, osteogenesis within the pellets slowly progressed over time, and by 9 weeks after insertion most of the pellet pores in both groups were filled with newly generated bone. The recombinant human BMP-collagen group, however, exhibited a significantly greater bone induction. These results indicated that if recombinant human BMP is used clinically in the future, artificially fabricated HAP would be a suitable carrier.

Analysis of Variance↗

Pneumocephalus caused by fistulas of the mastoid air cells treated with a temporoparietal fascial flap.

Using a temporoparietal fascial flap and hydroxyapatite ceramics, we treated a patient for complications after a neurosurgical operation for glossopharyngeal neuralgia. These consisted of pneumocephalus and cerebrospinal fluid rhinorrhea resulting from fistulas of mastoid air cells associated with a subcutaneous dead space. By means of the temporoparietal fascial flap, we were able to fill the dead space and reinforce the repaired dural and mastoid lesion as well. Hydroxyapatite ceramics were also useful for closing the mastoid air cell fistulas.

Bone Diseases↗

Bone induction of hydroxyapatite combined with bone morphogenetic protein and covered with periosteum.

Using a rabbit model, we evaluated the role of the periosteum in bone induction using hydroxyapatite ceramic pellets, some of which had been coated with bone morphogenetic protein. Eighteen rabbits were divided into two groups, a control group that received pellets soaked in phosphate-buffered saline alone and another group for which the pellets had been supplemented with bone morphogenetic protein. After making a skin incision on the head of each rabbit, two caudally pedicled periosteal flaps measuring 1 cm in width and 2.5 cm in length were elevated. These flaps were wrapped around hydroxyapatite pellets manufactured from limestone and fixed with sutures. After implantation, both groups of rabbits were returned to their cages, maintained for 3, 6, or 9 weeks [every group consisted of 3 rabbits (6 pellets)], and then sacrificed. In this study, the extent of bone induction, which was measured with a dual x-ray densitometer, that resulted from covering the hydroxyapatite pellet with periosteum alone (control group) was minimal. On the contrary, since osteogenesis from the periosteum toward the pores of the pellet was observed in the bone morphogenetic protein group much more than in the control group, the usefulness of our technique was confirmed. However, active osteogenesis was observed with subperiosteal implantation of the hydroxyapatite-bone morphogenetic protein complex in the bone morphogenetic protein group, but the osteogenesis observed was not distributed over the entire pellet.

Animals↗

A new operative method for treating severe cryptotia.

Results following surgical treatment for cryptotia are as yet far from fully satisfactory in cases in which deformity of the upper auricular portion is severe and particularly when there is contraction of the helical skin and auricular cartilage. Therefore, improvements in operative procedures have been considered necessary. We have developed a new method for treating cryptotia using a rhomboid flap in the superior and anterior auricular regions to correct the contraction of skin in the helix in cases in which the deformity of the upper auricular portion is large and shortening in the anterior and posterior directions is significant and in which severe contraction of the helix is observed. In this report, we describe the operative procedures used and present the relatively favorable results obtained in three patients. Using these techniques, we have been able to elongate the contracted helix frequently observed in cases of cryptotia by preparing a flap in the anterior auricular region. This approach appears to be a useful and safe means of treating cryptotia and so-called constricted ear as well.

Child, Preschool↗

Production and secretion of platelet-derived growth factor AB by cultured human keratinocytes: regulatory effects of phorbol 12-myristate 13-acetate, etretinate, 1,25-dihydroxyvitamin D3, and several cytokines.

Platelet-derived growth factor (PDGF) is a potent mitogen for several mesenchymal cells and plays an important role in wound repair. Three PDGF isoforms, PDGF-AA, PDGF-BB, and PDGF-AB, have been found to be generated in various tissues. PDGF-AB production by normal human keratinocytes (NHKs), by human squamous cell carcinoma cell line (HSC-1) cells, and by human dermal fibroblasts (HDFs) was studied in the presence of agents which influence cell growth. Both NHKs and HSC-1 cells spontaneously produced and secreted PDGF-AB. NHKs grown in keratinocyte growth medium produced more PDGF-AB than did those grown in keratinocyte basic medium. Phorbol 12-myristate 13-acetate inhibited PDGF-AB production in NHKs but promoted its production in HSC-1 cells. 1,25-dihydroxyvitamin D3 up-regulated PDGF-AB production, whereas etretinate did not. High levels of calcium in the culture medium induced little change in cellular PDGF-AB levels. Prostaglandin E1 slightly inhibited PDGF-AB production, transforming growth factor beta 1 promoted PDGF-AB production and interferon-gamma, interleukin-1 alpha, and tumor necrosis factor-alpha failed to exert any influence at all. Cultured HDFs did not produce any detectable PDGF-AB. These results suggest that keratinocytes are a major source of cutaneous PDGF and that this factor may therefore play an important role in wound repair and in certain proliferative skin diseases.

Carcinoma, Squamous Cell↗

Regulatory effects of gamma-interferon on IL-6 and IL-8 secretion by cultured human keratinocytes and dermal fibroblasts.

Gamma-interferon (IFN-gamma) is produced by T cells and plays an important role in immunological and inflammatory processes. To determine the effects of IFN-gamma on interleukin (IL)-6 and IL-8 secretion, normal human keratinocytes (NHKs), human squamous cell carcinoma cell line (HSC-1) cells, and human dermal fibroblasts (HDFs) were incubated with 100 U/ml of recombinant (r) IFN-gamma in the presence of various stimulants. HSC-1 cells and HDFs spontaneously secreted both IL-6 and IL-8 into the culture medium. NHKs secreted detectable levels of IL-8, but not of IL-6, and IL-8 secretion increased over 20 fold by stimulation with 10 nM of phorbol 12-myristate 13-acetate (PMA). rIFN-gamma inhibited IL-8 secretion in both HSC-1 cells and PMA-stimulated NHKs. On the other hand, it enhanced IL-1 alpha- and TNF alpha-induced IL-8 secretion in NHKs. In HDFs, rIFN-gamma inhibited IL-8 secretion, but enhanced secretion of IL-6, regardless of whether they were stimulated with IL-1 alpha or PMA. These results suggest that IFN-gamma has different regulatory effects on IL-6 and IL-8 secretion in NHKs and HDFs, depending on the stimulus.

Carcinoma, Squamous Cell↗

Differences in the expression of pemphigus antigens during epidermal differentiation.

Epidermal desmogleins with molecular weights of 130/140 kDa (Dsg3 or PVA) and 150/160 kDa (Dsg1 or DGI) are recognized by autoantibodies from patients with pemphigus vulgaris (PV) and pemphigus foliaceus (PF), respectively. In order to understand the histogenesis of both types of pemphigus, we studied the expression patterns of Dsg1 and Dsg3 during stratification of cultured keratinocytes. Monolayers of cultured normal human keratinocytes demonstrated uniform intercellular staining with PV sera. The staining pattern was distinct from the focal staining with PF sera observed only in the stratified areas. Both Dsg1 and Dsg3 proteins and their mRNA were expressed by the monolayers, whereas no production of Dsg2 (HDGC) mRNA was found. The relative ratio of Dsg3 to the total desmogleins, as determined by density on immunoblotting, decreased as the cultured keratinocytes stratified. In the completely stratified keratinocytes cultured on collagen membrane, Dsg1 became predominant, with subsequent reduction of PV antigen expression. The relative decrease of Dsg3 (PVA) during epidermal differentiation might be responsible for the induction of suprabasal acantholysis in PV.

Autoantigens↗

Diversity of immunobiological functions of T-cell lines established from patients with adult T-cell leukaemia.

In order to understand the variety of HTLV-1-associated cutaneous diseases, we studied the cytological profile of HTLV-1-infected T-cell lines established from patients with adult T-cell leukaemia (ATL). Among four CD4+ cell lines, termed 16T(-), 35T(-), MH-1, and KS-2, the 16T(-) cells secreted elevated quantities of IL-4, IL-6 and IFN-gamma and expressed mRNA for each cytokine in the absence of exogenous stimulation. The 35T(-) cells secreted IL-6 and a small amount of IFN-gamma, but not IL-4. The MH-1 and KS-2 cells secreted only IL-6 in the absence of stimulation. In response to stimulation with phorbol-12-myristate-13 acetate (PMA), the 16T(-) cells produced more IL-4 and IFN-gamma, whereas the 35T(-) and MH-1 cells exhibited increased secretion of IFN-gamma, but still no IL-4 or IL-4 mRNA production. Although neither IL-4 nor IFN-gamma were found in the culture supernatant of KS-2 cells, the production of IL-4 mRNA was detected by RT-PCR. Culture supernatants from the 16T(-) and 35T(-) cells induced the expression of intercellular adhesion molecule-1 (ICAM-1) and HLA-DR by cultured keratinocytes. This response was inhibited by pretreatment of the supernatant with anti-IFN-gamma antibodies. These results indicate that some HTLV-1-infected T-cell lines constitutively secrete various cytokines, including biologically active IFN-gamma. The diversity of immunobiological functions of the T-cell lines may be related to the variety of clinical features present in ATL patients.

Adult↗

Regulatory effects of antipsoriatic agents on interleukin-1 alpha production by human keratinocytes stimulated with gamma interferon in vitro.

It is known that keratinocytes produce and secrete interleukin-1 (IL-1) de novo and that this process can be enhanced by various stimulators. IL-1 has been shown to be a potent proinflammatory cytokine which mediates inflammation in various cutaneous disorders. It has also been demonstrated that gamma-interferon (IFN-gamma) which is released from infiltrated T cells can be detected in inflamed lesional sites. In order to understand the effects of IFN-gamma on IL-1 production by keratinocytes in such inflammatory lesions, normal human keratinocytes (NHKs) and human squamous cell carcinoma cell line (HSC-1) cells were cultivated with recombinant human IFN-gamma (rIFN-gamma) and IL-1 levels were measured by ELISA. The effects of antipsoriatic agents such as hydrocortisone (HC), cyclosporin A (CsA), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and its analogue MC903 on IL-1 production by keratinocytes were also investigated. IL-1 release by both NHK and HSC-1 cells was accelerated by stimulation with rIFN-gamma dose-dependently, although IL-1 alpha was released only transiently by rIFN-gamma-stimulated NHKs in serum-free keratinocyte growth medium containing HC. Antihuman IFN-gamma antibody inhibited IL-1 alpha release by HSC-1 cells stimulated with rIFN-gamma, suggesting that IL-1 alpha release from keratinocytes is upregulated by IFN-gamma. HC (5 micrograms/ml), 1,25(OH)2D3 (10(-6) M) and MC903 (10(-6) M), but not CsA (5 micrograms/ml), inhibited IL-1 alpha production by HSC-1 cells stimulated with 100 U/ml of rIFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗

[Early effects of intravenous steroid therapy on cell recruitment in sputum of chronic asthmatics].

Steroid is the key drug in the asthma therapy but not well known to play the role on the airway inflammatory cells. We examined sputum cells of acute excerbated 11 chronic adult asthmatics before and 2-3 hours after intravenous steroid and aminophylline therapy. There was no changes in the percent count of living cell, epithelial cell, metachlomatic cell, macrophage and neutrophil before and after treatment. Lymphocyte was 3.3 +/- 6.5% before and 2.6 +/- 2.0% after treatment. CD4 and CD25 double positive cell (CD4+/CD25+) was 0.7 +/- 0.5 and 1.2 +/- 0.9% and CD8+/CD25+ cell was 0.4 +/- 0.4 and 0.6 +/- 0.5% before and after treatment respectively. These changes were not significant. Eosinophil percent count did not decrease significantly but EG1+/EG2+ cell decreased from 6.7 +/- 7.8 to 4.3 +/- 5.2% significantly (p < 0.05). In the light of no decrease of activated T lymphocytes (CD25+ cells), we concluded that failure of tissue eosinophil response to lymphokines might result in a decrease in activated eosinophil count.

Adult↗

Regulatory effects of 1,25-dihydroxyvitamin D3 and a novel vitamin D3 analogue MC903 on secretion of interleukin-1 alpha (IL-1 alpha) and IL-8 by normal human keratinocytes and a human squamous cell carcinoma cell line (HSC-1).

Pro-inflammatory cytokines mediate their biological functions after they are secreted or released from intracellular to extracellular milieu. Keratinocytes have proven to be able to produce various cytokines including IL-1 and IL-8. Dysregulations of IL-1 and IL-8 were found in psoriatic lesions. Recently, vitamin D3 (VD3) was found to be an effective and safe therapy for psoriasis. In the present study, we investigated the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its analogue MC903 on IL-1 alpha and IL-8 secretion by human keratinocytes in vitro. Cultured normal human keratinocytes (NHKs) produced considerable amounts of IL-1 alpha but secreted less. In contrast, they produced less IL-8 and almost all molecules were secreted to the culture supernatants. Treatment of unstimulated NHKs with 1,25(OH)2D3 or MC903 showed little effects on IL-1 alpha production and secretion though they slightly enhanced IL-8. When NHKs were stimulated with tumour necrosis factor-alpha (TNF alpha), both IL-1 alpha and IL-8 secretions were enhanced and these enhancements were inhibited by 1,25(OH)2D3 or MC903. Stimulation of NHKs with phorbol 12-myristate 13-acetate(PMA) and lipopolysaccharide(LPS) resulted in an increase of IL-8 and decrease of IL-1 alpha in the culture supernatants. Addition of 1,25(OH)2D3 or MC903 inhibited the increased secretion of IL-8 but restored decreased secretion of IL-1 alpha from stimulated NHKs dose dependently. Hydrocortisone and cyclosporin A showed similar inhibitory effects on PMA/LPS-increased IL-8 secretion from NHKs but had little effect of restoring IL-1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗

Effects of cilostazol lotion on blood flow in rabbit skin.

Cilostazol (Cls) is a inhibitor of phosphodiesterase and increases cyclic AMP (cAMP) in platelets and also raises the vascular smooth muscle cell cAMP level causing vasodilation. Therefore, it was expected to increase local blood flow in the skin. Topical application of Cls may improve local blood flow without systemic effects in clinical situations. In this paper the effect of Cls lotion on skin blood flow was assessed in animal experiments. Application of this lotion allowed skin blood flow to remain at increased levels for about 60-90 min. Tissue assay of the Cls content revealed that Cls is absorbed percutaneously and retained, even in the inner tissue layer, for at least 180 min.

Administration, Cutaneous↗

Detection of Epstein-Barr virus genes in malignant lymphoma with clinical and histologic features of cytophagic histiocytic panniculitis.

T-cell proliferative disorders are occasionally associated with Epstein-Barr virus (EBV) infection. This study was designed to assess the clinical features of cutaneous lymphomas positive for EBV genes. Polymerase chain reaction was used to detect EBV genes in tissue or blood samples from patients with malignant lymphoma or related diseases. Of 26 DNA samples tested, EBV genes were detected in two samples, both of which were obtained from the same patient with subcutaneous T-cell lymphoma showing clinical and histologic features of cytophagic histiocytic panniculitis. On the basis of these findings, we conclude that EBV infection may be related to cutaneous lymphoma with hemophagocytic manifestations.

Adolescent↗

Method for preparing an exact-size model using helical volume scan computed tomography.

Helical volume scan computed tomography is a recently developed technology by means of which detailed data for most facial bone areas can be accumulated in a very short period, i.e., about 30 seconds, a much shorter time than required with conventional computed tomography. From a clinical standpoint, this is extremely important. In this report we discuss the principles of a method for preparing actual-size models by laser lithographic procedures based on data obtained by helical volume scan computed tomography. With these procedures, it is possible to obtain a good reproduction with high accuracy, on the order of 0.5 mm, not only of the outer morphologic structure of the cranial and maxillofacial bones but also of portions of the inner structure of cavities such as the cranium and paranasal sinuses. The difference between the original and model was under 3 percent, as confirmed by constructing a model of the dry skull with helical volume scan computed tomography. Therefore, production of exact-size models using helical volume scan computed tomography data represents an important technological development, breaking through previous limits imposed by conventional simulations prepared with three-dimensional images using CRT. With the combined use of laser lithographics and helical volume scan computed tomography, operative methods for craniomaxillofacial surgery should improve significantly in the near future.

Adult↗

Effects of etretinate on keratinocyte proliferation and secretion of interleukin-1 alpha (IL-1 alpha) and IL-8.

Etretinate has proven to be effective in the treatment of psoriasis. Since abnormal proliferation and cytokine secretion are well-known features of psoriatic epidermis, we studied the in vitro effects of etretinate on these two processes using human keratinocytes. Etretinate promoted proliferation of normal human keratinocytes (NHKs) grown in keratinocyte growth medium (KGM) but not in growth factor-deficient keratinocyte basic medium (KBM). Moreover, etretinate partly overcame growth inhibition by PMA. Etretinate was shown to have an effect on either IL-1 alpha or IL-8 secretion in unstimulated NHKs. In HSC-1, a human squamous cell carcinoma cell line cultured in 20% FCS/DMEM, inhibited IL-1 alpha secretion and enhanced IL-8 secretion. These results indicate that the effects of etretinate on keratinocyte proliferation and cytokine secretion may depend on cell type and culture conditions. Stimulation of NHKs with PMA significantly enhanced IL-1 alpha and IL-8 secretion, and these effects were inhibited by etretinate. However, etretinate failed to inhibit rTNF alpha-induced IL-8 secretion, suggesting that etretinate regulation of NHK cytokine secretion may also depend on the stimulus. As treatment of keratinocytes or epidermis with PMA can induce psoriasis-like changes, so might the experimental "anti-PMA" activity of etretinate be related to its therapeutic benefit in the treatment of psoriasis.

Carcinoma, Squamous Cell↗

Effects of prostaglandin E1 on human keratinocytes and dermal fibroblasts: a possible mechanism for the healing of skin ulcers.

The effects of prostaglandin E1 (PGE1) on cell growth, cytokine production and interaction of cultured normal human keratinocytes (NHKs) and human dermal fibroblasts (HDFs) were investigated. When NHKs were treated with PGE1 directly, only a slight increase in cell growth and a transient decrease in interleukin 1 alpha (IL-1 alpha) secretion were observed. No IL-6 was detected either before or after PGE1 treatment. In addition, IL-8 and transforming growth factor alpha (TGF alpha) production were uninfluenced by PGE1. The response of HDFs to PGE1 differed from that of NHKs. Following PGE1 treatment, IL-1 alpha and TGF alpha from HDFs remained undetectable while IL-6 production was enhanced markedly. IL-8 production was also slightly enhanced. Exposure of HDFs to PGE1 for 96 hours significantly promoted cell proliferation. Two kinds of conditioned media (CM) were prepared by a brief feeding of HDFs with keratinocyte basic medium or Dulbecco's modified Eagle's medium supplemented with 5% FCS with or without PGE1. NHKs proliferated more rapidly in CM than in corresponding basic medium. Moreover, CM prepared with PGE1 treatment showed a stronger effect in promoting NHK proliferation than CM without PGE1 treatment. This promoting effect was inhibited by anti-human IL-6 monoclonal antibody dose-dependently. These results indicate that fibroblasts are more sensitive than keratinocytes in response to PGE1 and that, upon PGE1 stimulation, HDF-derived IL-6 may play an essential role in NHK cell proliferation which may at least partly account for the beneficial effects of PGE1 in the treatment of cutaneous ulcerations.

Alprostadil↗

Regulation of pemphigus and desmosomal antigen expression by keratinocyte differentiation.

We studied in vivo binding sites of pemphigus antibodies and the expression of pemphigus and desmosomal antigens by keratinocytes in various culture periods. Both pemphigus vulgaris (PV) and pemphigus foliaceus (PF) antibodies mainly bound to the desmosomal areas of the lesional skin. Desmoglein and PV antigens co-localized on the cultured normal human keratinocytes in both monolayers and stratified areas. PF antigens, frequently together with involucrin and suprabasal keratins, were expressed by stratified keratinocytes. The Western blotting study demonstrated two different desmogleins with molecular sizes of 130 and 150 kD. The 130-kD desmoglein bore PV antigenic epitopes. The 150-kD band increased in volume as cultured keratinocytes stratified. PV antigen expression on the 130-kD desmoglein precedes PF antigen formation occurring in keratinocyte differentiation.

Antigen-Antibody Reactions↗