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Biomedical subjects

F Furukawa

Publications and source records attributed to F Furukawa.

At least 109 records · Page 6Linked to original sources
PubMed1996

Chemopreventive effects of 24R,25-dihydroxyvitamin D3, a vitamin D3 derivative, on glandular stomach carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.

The modifying effects of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], a vitamin D3 derivative, on glandular stomach carcinogenesis were investigated in male Wistar rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride exposure during the postinitiation phase. A total of 130 male 6-week-old rats was divided into five groups. Groups 1-3 (consisting of 30 rats/group) were given MNNG in drinking water at a concentration of 100 ppm and were simultaneously fed a diet supplemented with 10% NaCl for 8 weeks. They were fed a diet containing either 5.0 ppm (group 1) or 2.5 ppm (group 2) 24R,25(OH)2D3 or were kept on the basal diet alone (group 3) for the following 57 weeks. Rats in groups 4 and 5 were given 24R,25(OH)2D3, as were animals in groups 1 and 3, but did not receive the MNNG + NaCl treatment. The total incidence of combined atypical hyperplasias and adenocarcinomas in the glandular stomachs was significantly lower in group 1 (24%) than in group 3 (70%; P < 0.01). The mean numbers of atypical hyperplasias or adenocarcinomas of the glandular stomachs in groups 1 (0.31) and 2 (0.66) were also significantly decreased (P < 0.01 and P < 0.05, respectively) as compared to the group 3 value (1.21). Thus, the development of cancerous and precancerous lesions in the glandular stomach was decreased by exposure to 24R,25(OH)2D3 in a dose-dependent manner. Urinary calcium levels were increased by this vitamin D3 derivative (in line with the applied dose) when assayed at 10, 30, and 62 weeks, regardless of the MNNG + NaCl treatment The present results clearly indicate that 24,25(OH)2D3 exerts chemopreventive effects, possibly by influencing calcium pharmacodynamics, when given during the postinitiation phase of glandular stomach carcinogenesis in rats.

24,25-Dihydroxyvitamin D 3↗
PubMed1996

TCRV beta 7+ Th2 cells mediate UVB-induced suppression of murine contact photosensitivity by releasing IL-10.

In murine contact photosensitivity, a cutaneous delayed-type hypersensitivity reaction, preirradiation of the photosensitization site with UVB induced Ag-specific, afferent limb-acting, CD4+CD8- suppressor T cells (Ts). The present study examined usage of TCR V beta and production of immunosuppressive cytokines in Ts propagated in vitro. Spleen cells from UVB-preirradiated, 3,3',4',5- tetracholorosalicylanilide (TCSA)-photosensitized mice were stimulated with 3000-rad-irradiated lymph node cells (LNC) from TCSA/UVA-sensitized mice (LNCTCSA) in the presence of rIL-t. After several rounds of antigenic stimulation, a T cell line (B+TCL) consisted exclusively of CD3+CD4+CD8- V beta 7+ and V beta 13+ populations. Transfer to naive recipients of B+TCL treated with anti-V beta mAb plus complement revealed that the V beta 7+ cells suppressed both the in vivo and the in vitro aspects of contact photosensitivity to TCSA in an Ag-specific manner. The in vitro suppressive activity of B+TCL was neutralized by anti-IL-10 mAb, but not by anti-IL-4 mAb, indicating a crucial role of IL-10 in UBV-induced suppression. Upon stimulation with 3000-rad-irradiated-LNCTCSA, B+TCL released IL-4 and IL-10 but not IL-2, and V beta 7+ cells produced IL-10. The reverse transcriptase-PCR detected mRNA for IL-4 and IL-10 but not that for IL-2, IFN-gamma, or TGF-beta in B+TCL stimulated with or without concanavalin A. In accordance with the findings in B+TCL, spleen cells from UVB preirradiation plus TCSA/UVA mice contained V beta 7+ T cells that suppressed contact photosensitivity to TCSA and produced substantial amounts of IL-4 that provided a microenvironment for Th2 cell generation. We conclude that UVB preirradiation and photosensitization result in the generation of V beta 7+ Th2 cells that suppress contact photosensitivity by releasing IL-10. The dysfunction of effector Th1 cells underlying UVB suppression of delayed-type hypersensitivity seems to be due not only to altered APC function but also to counteraction of Th2 cells by Th1 cells.

Animals↗
PubMed1996

Ligand activation of overexpressed epidermal growth factor receptor results in colony dissociation and disturbed E-cadherin function in HSC-1 human cutaneous squamous carcinoma cells.

Various types of tumors show aberrant expression and overexpression of epidermal growth factor (EGF) receptor and the degree of receptor expression correlates with a malignant phenotype in many epithelial tumors. However, in vitro evidence supporting the advantageous role of receptor overexpression is deficient. In this study, we compared the effects of exogenous EGF on the cell colony morphology in monolayer and collagen gel culture between HSC-1 squamous carcinoma cells overexpressing EGF receptor and their revertant subline cells. These cells formed coherent cell colonies under routine culture conditions, but addition of EGF induced dissociation of cell colonies within 24 h in the parent HSC-1 cells, though not in the subline cells. Since the colony dissociation apparently involved loss of cell-cell adhesion, we also studied the effects of EGF on E-cadherin expression and its function. Cell aggregation assays showed that EGF reduced E-cadherin function dose-dependently in the parent cells, but not in the subline cells. However, immunoblotting analysis and ELISA showed the absence of downregulation or degradation of E-cadherin. Instead, EGF tyrosine phosphorylated cadherin/catenin complex components including beta-catenin and increased the detergent solubility of E-cadherin in the parent cells. These results suggest that EGF modified the functional association between E-cadherin and actin filament through tyrosine phosphorylation of the cadherin/catenin complex and thereby made the adhesion molecule incompetent. Our results indicate that the ligand activation of overexpressed EGF receptor impairs E-cadherin-mediated cell-cell adhesion and causes dissociation of the squamous carcinoma cell colonies, which facilitates tumor cell invasion in vivo. This might be relevant to the advantageous role of EGF receptor overexpression in malignant phenotype of epithelial tumor cells.

Cadherins↗
PubMed1996

Organ variation in the mutagenicity of dimethylnitrosamine in Big Blue mice.

Organ specificity in the lacI mutant frequency (MF) induced by dimethylnitrosamine (DMN) was analyzed in lung, liver, kidney, bone marrow, urinary bladder, and testis of Big Blue mice. Cell proliferative activity was also analyzed in some of these tissues by immunohistochemical staining of proliferating cell nuclear antigen (PCNA). Clastogenicity of DMN was concomitantly analyzed by the peripheral blood micronucleus assay with the same animals used for the lacI mutation assay. Five daily intraperitoneal (i.p.) treatments with DMN (1 mg/kg) increased MF in liver (6.2 x control), kidney (2.4 x control), and lung (2.1 x control). These are known target organs for DMN carcinogenesis. No MF increase was observed in nontarget organs studied, i.e., bone marrow, bladder, and testis. Single ip treatment with DMN also increased lacI MF in liver but the increases were smaller than in a 5-daily-treatment regimen. This result suggests that multiple dosing is more effective in the transgenic mutation assay. The enhancement of cell proliferation observed was in bronchial epithelia 7 days after treatment. No micronucleus induction in peripheral blood was observed 24 hours after 2 and 3 daily ip treatments with 1 mg/kg DMN. An increase in the incidence of micronucleated reticulocytes in peripheral blood was observed 48 hours after single ip treatment with 5 or 10 mg/kg DMN. The present study demonstrated organ-specific induction of gene mutations by DMN which suggests a relevance of this assay for the prediction of organ-specific carcinogenesis.

Animals↗
PubMed1996

Long-term toxicity/carcinogenicity study of L-histidine monohydrochloride in F344 rats.

The long-term toxicity and carcinogenicity of histidine, an essential amino acid for most animal species, were examined in Fischer 344 (F344) rats. Groups of 50 males and 50 females were given L-histidine monohydrochloride (HMHC) in their diet at concentrations of 0 (control), 1.25 and 2.5% for 104 wk; these dose levels were selected on the basis of the results of a subchronic toxicity study, in which body weights were depressed and formation of sperm granulomas in the epididymis was histologically evident in males fed 5.0% HMHC. All surviving rats were killed at wk 107. Increases in red blood cell count, haemoglobin value and haematocrit level were observed in male rats given 2.5% HMHC. A variety of tumours developed in all groups, including the control group, but all the neoplastic lesions were histologically similar to those known to occur spontaneously in this strain of rats, and no statistically significant increase in the incidence of any tumor was found in the treated groups of either sex. Thus, it was concluded that, under the present experimental conditions, HMHC is not carcinogenic in F344 rats.

Administration, Oral↗
PubMed1996

Inhibitory effects of the dietary antioxidants butylated hydroxyanisole and butylated hydroxytoluene on bronchioloalveolar cell proliferation during the bleomycin-induced pulmonary fibrosing process in hamsters.

The effects of dietary antioxidants on bleomycin (BLM)-induced pulmonary fibrosis were investigated in Syrian golden hamsters. In addition, the influence on cell proliferative activity in bronchioloalveolar hyperplastic lesions during the lung fibrosing process was evaluated in terms of argyrophil nucleolar organizer regions (AgNORs) and proliferating cell nuclear antigen (PCNA). Male 6-wk-old hamsters were divided into six groups. Groups 1-3 were intratracheally instilled with BLM at a dose of 2.5 U/kg body weight on days 0 and 14, and then given a diet supplemented with 1% butylated hydroxyanisole (BHA), or 1% butylated hydroxytoluene (BHT), or basal diet alone for the following 41 days. Groups 4-6 were given 1% BHA, 1% BHT or basal diet without BLM treatment for the same time period as that in those of groups 1-3. The mortality rate of animals in group 1 (BLM/BHA) (one in 20; 5%) was lower than in those of groups 2 (BLM/BHT) (three in 20; 15%) and 3 (BLM alone) (four in 20; 20%). BHA and BHT treatments significantly inhibited lung weight gains by BLM (P < 0.05). Histopathologically, both BHA and BHT reduced BLM-induced pulmonary histopathological changes such as fibrosis, macrophage aggregation and epithelial proliferation, with a tendency for correlation with accumulation of type III collagen. In addition, antioxidant treatment significantly lowered the mean numbers of AgNORs (P < 0.01) and PCNA-labelling indices (P < 0.05) in the hyperplastic bronchioloalveolar lesions. The results thus indicate that these antioxidants exert inhibitory effects on proliferation of hyperplastic lesions associated with lung fibrosis.

Animals↗
PubMed1996

E- and P-cadherin expression in tumor tissues and soluble E-cadherin levels in sera of patients with skin cancer.

The expression pattern of epithelial (E)- and placental (P)-calcium-dependent cell-cell adhesion molecules was examined immunohistochemically in various skin tumors. E- and P-cadherin expression was preserved in nodular and superficial types of basal cell carcinoma (BCC). In well-differentiated squamous cell carcinoma (SCC), E-cadherin on the cell surface of the tumor was reduced but expression of P-cadherin was preserved more frequently at the peripheral sites of the tumor than in the central sites of the tumor. Paget's cells and melanoma cells did not express E- or P-cadherins in the nest of the epidermis. Immunoreactive E-cadherin levels in sera were significantly elevated in patients with invasive Paget's disease, metastatic malignant melanoma and severe types of psoriasis and atopic dermatitis when compared with those of normal controls. Reduced or loss of cadherin in localized tumor cells may be correlated with the proliferation, and the level of soluble E-cadherin in circulation may be a marker in the extent of damaged skin by tumor and/or inflammation.

Cadherins↗
PubMed1996

CD7-positive Sézary syndrome with a Th1 cytokine profile.

Sézary syndrome is a leukemic variant of cutaneous T-cell lymphoma characterized by the appearance of numerous CD4+ cells with cerebriform nuclei in the peripheral blood. Recent observations have suggested that Sézary cells lack CD7 molecules on their surface and are analogous to murine Th2 cells. It remains unclear, however, whether these two properties are actually common features of Sézary cells. We describe a case of Sézary syndrome in which more than 98% of the peripheral blood mononuclear cells expressed CD7 as well as a homogeneous T-cell receptor V alpha 2V beta 17, indicative of the expression of CD7 in the Sézary cells. Although the circulating Sézary cells continuously bore CD7 molecule on their surface throughout the patient's clinical course, the intensity of CD7 expression was variable in skin-infiltrating and in vitro cultured cells. Peripheral blood mononuclear cells from the patient proliferated well to a V beta 17-relevant superantigen (staphylococcal enterotoxin B) but not to irrelevant superantigens; produced interleukin-2, interferon gamma, and tumor necrosis factor-alpha, but not interleukin-4; and transcribed messenger RNA for interleukin-2 and interferon gamma but not interleukin-4 or interleukin-10. This represents an unusual case of a CD7+ Sézary syndrome with a cytokine profile characteristic of Th1 cells.

Antigens, CD7↗
PubMed1996

Chemopreventive effects of phenethyl isothiocyanate on lung and pancreatic tumorigenesis in N-nitrosobis(2-oxopropyl)amine-treated hamsters.

The chemopreventive effects of phenethyl isothiocyanate (PEITC) were investigated in N-nitrosobis(2-oxopropyl)-amine (BOP)-treated hamsters. Female 5-week-old Syrian golden hamsters were divided into six groups. Animals in groups 1-3, each consisting of 30 hamsters, were given BOP by two subcutaneous injections 7 days apart at a dose of 20 mg/kg body weight, plus either 100, 10 or 0 micromol of PEITC in corn oil by gavage 2 h prior to each BOP treatment, respectively per group. Animals in groups 4 and 5, each consisting of 10 hamsters, were given 100 and 10 micromol of PEITC alone in corn oil, and 10 animals in group 6 served as a vehicle control. Animals were sacrificed 52 weeks after the first BOP injection. Both the incidences and multiplicities of lung adenomas and/or adenocarcinomas were significantly decreased in a dose-dependent manner by PEITC treatments (P < 0.01 or 0.05). The lung tumor incidences were inhibited by 100% with 100 micromol PEITC and by 82% with the 10 micromol dosage. In addition, the high dose of PEITC also significantly inhibited pancreatic carcinogenesis (P < 0.05) and showed a tendency to lower the incidences of liver and renal tumors, although these effects were not statistically significant. Under the present experimental conditions, PEITC itself did not cause any apparent toxicity. Our results thus indicate that PEITC is a remarkably effective chemopreventive agent for the BOP-induced lung and pancreatic tumors in hamsters.

Adenocarcinoma↗
PubMed1996

Th2 suppressor cells are more susceptible to sphingosine than Th1 cells in murine contact photosensitivity.

Murine contact photosensitivity (CPS) to 3,3',4',5-tetrachlorosalicylanilide (TCSA) is a cutaneous delayed-type hypersensitivity reaction in which both positive and negative regulatory pathways exist. The latter pathway is mediated by antigen-specific, CD4+ suppressor T cells (CPS-Ts) that are Th2 cells. We examined the effects of sphingosine and synthetic cell-permeable analogs of ceramide on the cellular kinetics of CPS-Ts and immune lymph node cells from TCSA-photosensitized mice (CPS-LNC), along with other murine T-cell populations. The addition of sphingosine at 10 or 3 microM to in vitro cultures suppressed DNA synthesis of CPS-Ts and Th2 clones, including D10 cells and 24-2 cells, but not that of CPS-LNC or Thl clones, including 23-1-8 and 28-4 cells. This suggested that sphingosine exerts its inhibitory effects preferentially on the proliferation of Th2 cells. Although suppressing DNA synthesis, sphingosine augmented the production and mRNA expression of interleukin-4 (IL-4) and enhanced the expression of the IL-4 receptor in CPS-Ts. In addition, the ability of sphingosine to induce signal transduction of CPS-Ts was confirmed by elevation of the intracellular free Ca++ concentration. Because CPS-Ts exposed to sphingosine exhibited a lower G2M/G1 ratio than control, these seemingly ambivalent phenomena may be caused by retardation of the G1 to S phase progression, a cell-cycle dysregulation known to augment cytokine production. In contrast to sphingosine, cell-permeable ceramide did not affect the proliferation of these cells when stimulated with mitogen/antigen and did not augment IL-4 production by CPS-Ts. Our study suggests that sphingosine modifies the Th1/Th2 balance by preferentially affecting the cellular kinetics of Th2.

Allergens↗
PubMed1996

Spontaneous autoimmune skin lesions of MRL/n mice: autoimmune disease-prone genetic background in relation to Fas-defect MRL/1pr mice.

The autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mouse is characterized by the lpr mutation, which is a defect in the Fas antigen. Since Fas mediates apoptosis, this defect results in CD4-CD8- double negative T-cell proliferation, lupus nephritis, and macroscopic lupus erythematosus-like skin lesions. The control counterpart of MRL/lpr mouse is the MRL/Mp-+/+ (MRL/n) mouse, which lacks the lpr mutation and is almost normal during the first 6 mo of life. The lpr mutation, however, accelerates autoimmune phenomena in MRL/lpr mice. Thus, it is important to investigate autoimmune diseases like systemic lupus erythematosis in relation to the autoimmune disease-prone genetic background of MRL/n mice. We found that skin lesions in aged MRL/n mice had unique characteristics. The first characteristic is spontaneous occurrence, and the second is epidermal cell nuclear immunostaining with IgGs by direct immunofluorescence. The skin lesions in aged MRL/n mice showed milder inflammation than in MRL/lpr mice. A homogeneous pattern of epidermal cell nuclear staining was always associated with nuclear staining in kidney cells and also correlated with the in vitro binding of sera to keratinocytes cultured from newborn MRL/n mice. These results suggest that the skin lesions of aged MRL/n mice are a good model for certain types of cutaneous lupus erythematosus and also can provide new insights into the long-standing controversy whether epidermal cell nuclear staining occurs in vivo.

Aging↗
PubMed1996

Th2 cytokine mRNA expression in primary cutaneous CD30-positive lymphoproliferative disorders: successful treatment with recombinant interferon-gamma.

Primary cutaneous CD30 (Ki-1)+ large cell lymphoma (KiL) and lymphomatoid papulosis (LyP) type A are collectively termed as primary cutaneous CD30-positive lymphoproliferative disorders. We examined the cytokine profile of skin-infiltrating cells and the therapeutic efficacy of recombinant interferon-gamma (rIFN-gamma) in primary cutaneous KiL and LyP type A. By reverse transcriptase-polymerase chain reaction, mRNAs for interleukin-4 (IL-4) and IL-10 were detected in the dermis of skin lesions in all cases (three cases of KiL and four cases of LyP). In addition, tissue from one KiL patient transcribed IL-2 and IFN-gamma messages, and one LyP patient showed IL-2 mRNA. In contrast, normal skin from ten healthy donors contained mRNA for IL-2 or IFN-gamma, or both, but not for IL-4. Before the therapeutic trial of rIFN-gamma, the response of skin lesions was assessed by a predictive skin test with local injection of rIFN-gamma (0.5 x 10(6) Japan Reference Units [JRU; 1 JRU roughly corresponds to 4 NIH units]) for 3 consecutive days in two KiL and two LyP patients. Numbers of skin-infiltrating CD30+ cells were decreased, and transcription of mRNA for IL-4 and IL-10 was downregulated after the skin test in one KiL and two LyP cases. One KiL patient showed no histologic response or change in mRNA expression. In the therapeutic trial, rIFN-gamma (total doses of 1.2-4.0 x 10(7) JRU) was administered intravenously (n = 2) or locally (n = 2). In three patients who responded to the skin test, the lesions were objectively improved and the numbers of skin-infiltrating CD30+ cells were markedly decreased after the therapeutic trial. No improvement was observed in one KiL patient who did not respond to the skin test. These findings suggest that the skin-infiltrating CD30+ cells in KiL and LyP have a Th2 cytokine profile and raise the possibility that the administration of rIFN-gamma improves the conditions by inhibiting cytokine mRNA transcription and proliferation of CD30+ cells.

Aged↗
PubMed1996

Inhibitors of sphingolipid synthesis modulate interferon (IFN)-gamma-induced intercellular adhesion molecule (ICAM)-1 and human leukocyte antigen (HLA)-DR expression on cultured normal human keratinocytes: possible involvement of ceramide in biologic action of IFN-gamma.

To elucidate the participation of sphingosine and ceramide in the biologic action of cytokines on epidermal keratinocytes, we studied whether inhibitors of sphingolipid synthesis modulate interferon (IFN)-gamma-induced intercellular adhesion molecule (ICAM)-1 and human leukocyte antigen (HLA)-DR expression on cultured normal human keratinocytes. Pretreatment of keratinocytes with L-cycloserine or fumonisin B1, but not 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), significantly suppressed both ICAM-1 and HLA-DR expression induced by IFN-gamma. Because the synthesis of all kinds of sphingolipids is blocked by L-cycloserine and all except that of sphinganine by fumonisin B1, whereas PDMP inhibits the synthesis of glucosylceramide and glycosphingolipids, the result suggests the participation of ceramide and/or sphingosine in IFN-gamma-induced ICAM-1 and HLA-DR expression. Exogenous C2-ceramide reversed the effects of L-cycloserine and fumonisin B1. On the other hand, sphingosine reversed the effect of L-cycloserine, but not of fumonisin B1. These results indicate that ceramide participates in this pathway, as fumonisin B1, but not L-cycloserine, inhibits the synthesis of ceramide from sphingosine. In addition, reverse transcriptase polymerase chain reaction showed that L-cycloserine reduced the mRNA for ICAM-1, HLA-DR alpha, and HLA-DR beta induced by IFN-gamma, and C2-ceramide and sphingosine antagonized the effect of L-cycloserine. Furthermore, the degradation rate of fluorescent sphingomyelin into ceramide in keratinocytes was increased by IFN-gamma, suggesting that IFN-gamma activates sphingomyelin hydrolysis in keratinocytes. These observations suggest the possible role of ceramide in IFN-gamma-induced ICAM-1 and HLA-DR expression on keratinocytes. Ceramide may function as an endogenous modulator mediating the cytokine signals in keratinocytes.

Base Sequence↗
PubMed1996

Selective expansions of T cells expressing V beta 8 and V beta 13 in skin lesions of patients with chronic cutaneous lupus erythematosus.

There are several clinical types of cutaneous lupus erythematosus (LE), including acute cutaneous LE (ACLE), which occurs in 50-60% of patients with systemic LE (SLE), chronic cutaneous LE (CCLE), which is almost the same as discoid LE (DLE), and subacute cutaneous LE (SCLE). Although several important hypotheses have been proposed to explain cutaneous LE, the pathomechanisms still remain complicated and obscure. Of special interest is whether and how the T cell receptor (TCR) repertoire of infiltrating lymphocytes is involved in the development of the different types. To address this issue, we immunohistochemically examined the V beta usage of infiltrating T cells in skin lesions, as well as in peripheral blood mononuclear cells (PBMC) of patients with cutaneous LE. The number of V beta 3.1 CD3+ cells in the PBMC of patients with ACLE and CCLE was significantly lower than in controls. In contrast, the number of V beta 3.1 CD3+ cells was elevated in the skin lesion of CCLE over that in psoriasis vulgaris or atopic dermatitis. Furthermore, skin lesions in CCLE patients showed a higher incidence of V beta 8.1 CD3+ and V beta 13.3 CD3+ cells than did those in ACLE patients. These results suggest that skin lesions of CCLE are oligoclonally associated with selective expansions of TCR V beta chains and may be induced by antigen stimuli, including superantigens.

CD3 Complex↗
PubMed1996

Acne fulminans coexisting with pyoderma gangrenosum-like eruptions and posterior scleritis.

A 30-year-old Japanese man presented with an erythematous, papulonodular eruption on his face and upper trunk, which rapidly progressed into severely exuberant, ulcerative lesions with a confluent tendency. His other symptoms included a high fever and general malaise. Complete blood cell counts showed neutrophilia with increased percentages of myelocytes and metayelocytes. The systemic administration of corticosteroids improved his skin lesions, leaving scars and milia. During tapering of corticosteroids, however, the patient developed posterior scleritis of his eyes and pyoderma gangrenosum-like eruptions on the lower legs. Our patient's history suggests that pyoderma gangrenosum-like eruptions and posterior scleritis are disorders associated with acne fulminans.

Acne Vulgaris↗
PubMed1996

Evaluation of sialyl Lewisx antigen in the skin and the sera of patients with psoriasis vulgaris.

The roles of sialyl-Lewisx antigen were evaluated in the pathogenesis of psoriasis. Sialyl-Lewisx expression was investigated immunohistochemically in the epidermis of normal human skin and erythematous lesional skin of psoriasis vulgaris by avidin-biotin-peroxidase complex procedures. A few sialyl-Lewisx positive dendritic cells were detected in the epidermis of normal human skin. In 7 out of 9 cases of psoriasis vulgaris, the number of sialyl-Lewisx-positive epidermal dendritic cells increased in the erythematous lesion over the adjacent normal skin; there were no marked changes in the numbers of CD1a-positive cells in the epidermis between the two skin types. In the double immunofluorescence studies, more than half of the sialyl-Lewisx-positive epidermal cells in psoriatic erythema were stained with a monoclonal Lag antibody that specifically reacts with Birbeck granules and related structures of human Langerhans cells. Furthermore, we determined the changes in serum levels of sialyl-Lewisx antigens in patients with psoriasis. Although levels in the sera were not significantly elevated over those of controls, the increases correlated with the degree of disease activity. These findings suggest that sialyl-Lewisx antigen is possibly involved in the development of psoriasis.

Biopsy, Needle↗
PubMed1996

Prevention by 2-mercaptoethane sulfonate and N-acetylcysteine of renal oxidative damage in rats treated with ferric nitrilotriacetate.

Ferric nitrilotriacetate (Fe-NTA) is a renal toxicant and carcinogen in rats and mice. We found that its administration results in formation of 4-hydroxy-2-nonenal (HNE) in the renal proximal tubule cells of rats, and 8-hydroxydeoxyguanosine (8-OHdG) adducts in their DNA, suggesting a role for oxidative stress. Since 2-mercaptoethane sulfonate (MESNA) and N-acetylcysteine (NAC), administered orally, have been shown to increase the kidney levels of free thiol groups, their influence on the renal toxicity and carcinogenicity induced by Fe-NTA was examined in the present study. Male Wistar rats were intraperitoneally injected with Fe-NTA (12 mg Fe/kg), and MESNA (100 mg/kg) or NAC (200 mg/kg) was given orally 1 h before and 1 h after this treatment. The animals were killed for tissue analyses 3 h after the Fe-NTA exposure. In accord with our previous reports, HNE-modified protein was detected in the proximal tubules of Fe-NTA-treated rats by means of immunohistochemistry. Likewise, levels of 8-OHdG in the renal nuclear DNA, lipid peroxides as thiobarbituric acid-reactive substances in the kidneys, and blood urea nitrogen and creatinine in the serum were significantly increased by the Fe-NTA treatment. All of these changes were completely inhibited by oral administration of MESNA or NAC. These results suggest that both of these compounds can prevent the oxidative stress induced by Fe-NTA.

8-Hydroxy-2'-Deoxyguanosine↗