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C Nishigori

Publications and source records attributed to C Nishigori.

At least 19 recordsLinked to original sources
PubMed2006

Overexpression of IL-8 in the cornea induces ulcer formation in the SCID mouse.

AIMS: Although interleukin 8 (IL-8) is not produced in the normal cornea, it has been detected there in several pathological conditions. In this study, the direct effects of IL-8 overexpression on the cornea was examined. METHODS: The corneal surface of severe combined immunodeficiency mice was infected by the adenovirus vector encoding human IL-8 (IL-8/Ad5) and clinical and pathological changes were observed at various time points. RESULTS: Clinically, marked angiogenesis and ulcer formation in the cornea were observed by 12 hours and 24 hours, respectively. Histologically, prominent angiogenesis was observed in the corneal stroma at 12 hours. Cleft formation between the corneal epithelium and stroma, and neutrophil infiltration into the corneal stroma were seen at 16 hours. By 24 hours after the infection with IL-8/Ad5, a shallow ulcer was formed in the cornea. In contrast, infection with the control adenovirus carrying the beta galactosidase gene (LacZ) showed neither corneal ulceration nor neutrophil infiltration. Immunohistochemical analysis showed that infection with IL-8/Ad5 resulted in the production of IL-8 by corneal and conjunctival stromal cells. CONCLUSION: Our results indicate that IL-8 overexpression in corneal tissue causes ulcer formation in the cornea through chemoattraction of neutrophils, suggesting the aetiological role of IL-8 in some types of corneal ulcers.

Adenoviridae↗
PubMed2006

The inhibition spectrum of solar urticaria suppresses the wheal-flare response following intradermal injection with photo-activated autologous serum but not with compound 48/80.

BACKGROUND: The inhibition spectrum (IS) in solar urticaria was identified mainly in Japanese patients with solar urticaria, although the mechanism of action of the IS has not been elucidated. METHODS: Because an intradermal injection of action spectrum (AS)-irradiated serum in a case of solar urticaria induced a wheal response, we studied the responsiveness of the intradermal injection after an IS irradiation. RESULTS: An AS in this patient was composed of visible light shorter than 500 nm, while an IS was composed of visible light longer than 530 nm. When the IS was exposed immediately after the AS irradiation, the wheal response was inhibited. However, when the IS was exposed before the AS irradiation, the wheal response was not inhibited. An intradermal injection of her serum produced no reaction, whereas an intradermal injection of her serum pre-irradiated with visible light induced a wheal flare response. Further examination revealed that the in vivo wheal-inducing activity of her serum irradiated with visible light could be attenuated by post-IS irradiation at the injection site, while the wheal-inducing activity of her visible light-irradiated serum was not inhibited by irradiation of the activated serum with the IS. The wheal-flare response induced by compound 48/80 and histamine was not altered by IS irradiation at the site of skin tests. CONCLUSION: These findings indicate that photoallergens in the patient's serum that are activated by visible light irradiation are responsible for the development of her symptoms and that the IS may suppress the wheal response by inhibiting the binding of the photoallergens to mast cells, not by inactivating the photoallergens and stabilizing mast cells.

Aged↗
PubMed2005

Retinoic acid suppresses telomerase activity in HSC-1 human cutaneous squamous cell carcinoma.

BACKGROUND: Activation of telomerase is crucial for the continued growth and progression of cancer cells. In a previous study, we showed that telomerase is frequently activated in skin tumours. OBJECTIVE: Because retinoic acid (RA) plays an important role in the growth and differentiation of keratinocytes and as RA has some preventive and therapeutic effects on human skin cancers, we examined the effect of RA on the telomerase activity of HSC-1 human cutaneous squamous cell carcinoma cells. RESULTS: Treatment of HSC-1 cells with all-trans RA (ATRA) significantly suppressed their telomerase activity. The suppression of telomerase activity was obvious at day 4 and was maximal at day 5 after the start of treatment with RA. This suppression was reversible as removal of ATRA allowed the recovery of telomerase activity. The suppression of telomerase activity correlated with the decreased expression of mRNA of human telomerase catalytic subunit (hTERT), the rate-limiting determinant of enzyme activity. The production of c-myc and of Sp1 proteins, transcription factors regulating hTERT expression, was not suppressed in HSC-1 cells by ATRA, but phosphorylation of extracellular signal-regulated kinases (ERK)1/2 and of the serine/threonine kinase Akt was significantly suppressed. Phosphorylation of the epidermal growth factor receptor, which regulates hTERT expression in HSC-1 cells, was not altered by ATRA. CONCLUSIONS: These data indicate that RA is effective in inhibiting telomerase activity in HSC-1 cells. Suppression of ERK1/2 and Akt activation is presumed to be involved in the RA-induced suppression of hTERT.

Carcinoma, Squamous Cell↗
PubMed2005

Impaired removal of 8-hydroxydeoxyguanosine induced by UVB radiation in naevoid basal cell carcinoma syndrome cells.

BACKGROUND: The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by tumorigenesis such as multiple basal cell carcinomas, odontogenic keratocysts and developmental abnormalities such as calcified dural folds and rib-anomalies. Recently, it has been shown that ultraviolet (UV) B exposure produced more BCCs in ptch knockout mice than wild mice. OBJECTIVES: To Investigate the role of UV in development of BCCs in NBCCS, cellular sensitivity to killing by UVB and removal of UVB-induced oxidative DNA damage were examined using fibroblasts derived from patients with NBCCS under physiologically relevant doses of UVB exposure. PATIENTS AND METHODS: Three patients with NBCCS, a 59-year-old male patient, an 18-year-old boy and a 13-year-old boy were examined by photobiological analysis. Cellular sensitivity to killing by UVB and UVC and removal of oxidative DNA damage caused by UVB were tested using fibroblasts derived from these patients. We measured cellular 8-hydroxydeoxyguanosine (8-OHdG) after UVB exposure up to 24 h after UVB exposure using high-performance liquid chromatography. RESULTS: All three cell strains derived from the patients with NBCCS were hypersensitive to killing by UVB (D10: 50-70% of normal) but not by UVC. After UVB exposure, the production of 8-OHdG increased dose dependently up to 3200 J m-2 in both NBCCS cells and normal cells. In normal cells, 8-OHdG after UVB exposure returned to its basal level during 24 h, whereas in NBCCS cells the amount of 8-OHdG after 800 J m-2 of UVB exposure did not return to its basal level even after 24 h. The result indicates the removal of 8-OHdG could be impaired in NBCCS cells. Ability in removal of thymine dimers of NBCCS cells was similar to that of normal cells. CONCLUSIONS: Hypersensitivity to UVB can be one of the diagnostic tools of NBCCS for those whose clinical features have not yet completed. Hypersensitivity to cell killing and the impairment of removal of 8-OHdG after UVB exposure may play some role in developing BCCs and other tumours in NBCCS.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Useful applications of DNA repair tests for differential diagnosis of atypical dyschromatosis symmetrica hereditaria from xeroderma pigmentosum.

Dyschromatosis symmetrica hereditaria (DSH) is a hereditary skin disease characterized by the presence of pigmented and hypopigmented macules on the extremities and freckles on the face. However, if clinical features are not fully developed in infantile patients, it is difficult to differentiate DSH from xeroderma pigmentosum by clinical features alone. A 2-year-old boy (patient 1), revealed atypical features of DSH with slight susceptibility to sunburn. However, his grandfather (patient 4) who was 67 years old, revealed typical features of DSH, which helped to make an exact diagnosis in patient 1. For patient 2, a 5-year-old boy, and patient 3, a 3-year-old girl, it was more difficult to make a diagnosis because there were no family members with DSH features. DNA repair ability was tested for all four cases by means of unscheduled DNA synthesis and colony formation of skin fibroblasts after ultraviolet light irradiation, which resulted in an accurate diagnosis of DSH. We propose that these tests be performed to make a diagnosis of DSH in the case of poor or atypical clinical symptoms.

Aged↗
PubMed2001

Angiosarcoma of the scalp: absence of vascular endothelial cadherin in primary and metastatic lesions.

A 73-year-old man with angiosarcoma of the scalp died about 1 year after disease onset, despite systemic and topical administration of recombinant interleukin-2. Histopathology showed typical changes of endothelial cells with very sparse lymphocytic infiltration into the tumour. An autopsy revealed that the primary site penetrated cranial bone and invaded vertically into the subarachnoid space. Multiple metastases to lung, chest wall, vertebrae and ribs were also found. On immunofluorescence staining, the expression of vascular endothelial cadherin, which is present in normal endothelium, was absent from both primary and metastatic sites. This may have promoted local invasion and metastasis.

Aged↗
PubMed2001

Churg-Strauss syndrome with renal involvement: a case report.

We report a case of Churg-Strauss syndrome with renal involvement. A 51-year-old woman was admitted to our hospital in April of 1999 complaining of abdominal pain and severe diarrhea followed by multiple purpura on both legs. A diagnosis of Churg-Strauss syndrome was made on the basis of the presence of preceding asthma, eosinophilia, increased IgE, and the histological findings of a biopsy taken from the purpura. Creatinine clearance level at admission was low (43.3 ml/min) and urinalysis revealed proteinuria and microscopic hematuria. These abnormalities were improved with systemic steroid therapy. Renal involvement seems to be more common than previously reported in Churg-Strauss syndrome.

Churg-Strauss Syndrome↗
PubMed2000

UV-induced DNA damage in carcinogenesis and its repair.

The purpose of this study is to ask what kind of DNA damage is involved in UV carcinogenesis. Firstly, ras gene alterations were analyzed in UV-induced mice skin cancers. Five types of base changes resulting in activated ras were detected in nine UV-induced skin cancers. Unexpectedly, transversions predominated, whereas previous findings using shuttle vectors indicated that UVC predominantly causes transition-type mutations, which implies the involvement of DNA damage other than dimers in UV carcinogenesis in vivo, in the presence of endogenous photosensitizers. Secondly, we detected mutations both in p53 and ras of skin cancers from patients with xeroderma pigmentosum (XP). Fifty percent of non-melanoma-skin cancers (NMSCs) from XP patients had mutations in p53. The mutation occurred preferentially at CC sites and transitions predominated for p53, whereas ras mutations were far less frequent over the same samples, indicating that DNA damage caused by sunlight rarely hits the crucial sites of ras. Lastly, p53 mutations on NMSCs were compared between sun-exposed area and non/less sun-exposed area. The frequency of p53 mutations between these two groups were almost comparable. However, 67% had the transition at dipyrimidine sites in NMSCs from sun-exposed area, whereas only 20% had the same type of mutations from non/less exposed area (P<0.05).

Animals↗
PubMed1999

The role of oxidative DNA damage in human arsenic carcinogenesis: detection of 8-hydroxy-2'-deoxyguanosine in arsenic-related Bowen's disease.

Arsenic is widely distributed in nature in the form of either metalloids or chemical compounds, which cause a variety of pathologic conditions including cutaneous and visceral malignancies. Recently, reactive oxygen species have been hypothesized to be one of the causes of arsenic-induced carcinogenesis. 8-Hydroxy-2'-deoxyguanosine is one of the major reactive oxygen species-induced DNA base-modified products that is widely accepted as a sensitive marker of oxidative DNA damage. We studied the presence of 8-hydroxy-2'-deoxyguanosine by immunohistochemistry using N45.1 monoclonal antibody in 28 cases of arsenic-related skin neoplasms and arsenic keratosis as well as in 11 cases of arsenic-unrelated Bowen's diseases. The frequency of 8-hydroxy-2'-deoxyguanosine positive cases was significantly higher in arsenic-related skin neoplasms (22 of 28; 78%) than in arsenic-unrelated Bowen's disease (one of 11; 9%) (p < 0.001 by chi2 test). 8-Hydroxy-2'-deoxyguanosine was also detected in normal tissue adjacent to the arsenic-related Bowen's disease lesions. Furthermore, arsenic was detected by neutron activation analysis in the deparaffined skin tumor samples of arsenic-related disease (four of five; 80%), whereas arsenic was not detected in control samples. Our results strongly suggest the involvement of reactive oxygen species in arsenic-induced human skin cancer. Key word: neutron activation analysis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

HindIII liposomes suppress delayed-type hypersensitivity responses in vivo and induce epidermal IL-10 in vitro.

Considerable evidence suggests that ultraviolet-B (UV-B) radiation suppresses certain immune responses through the induction of cyclobutane pyrimidine dimers in DNA. To determine whether induction of other forms of DNA damage in the skin mimicked the immunosuppressive effects of UV-B radiation, we produced double-strand breaks in the DNA of epidermal cells with HindIII restriction endonuclease encapsulated in liposomes. Application of these liposomes, but not liposomes containing inactive HindIII or an irrelevant endonuclease, to the skin of C3H mice suppressed the induction of delayed-type hypersensitivity responses to Candida albicans and alloantigen and induced IL-10 production in the epidermis. Treatment of the Pam212 murine keratinocyte cell line with these liposomes in vitro induced immunosuppressive activity and IL-10 in culture supernatants. Unlike UV-B irradiation, however, HindIII in liposomes failed to induce suppressor T cell activity in vivo or in vitro. We conclude that double-strand breaks in DNA of epidermal cells can induce immunosuppression and up-regulate the production of immunomodulatory cytokines; however, either DNA damage alone does not account for all the immunosuppressive properties of UV-B irradiation, or cyclobutane pyrimidine dimers differ qualitatively from double-strand breaks in their biologic consequences. These studies raise the possibility that drugs causing DNA damage may induce cytokine dysregulation and immune suppression in addition to cytotoxicity.

Animals↗
PubMed1998

Mutations of p16 and p15 tumor suppressor genes and replication errors contribute independently to the pathogenesis of sporadic malignant melanoma.

Mutations of p16 and p15 suppressor oncogenes and the replication errors in six microsatellite loci in sporadic malignant melanomas were analyzed. Four (9.1%) homozygous deletions of both p16 and p15 genes and one point mutation (2.3%) in the p15 gene were detected among 44 primary melanoma samples. One mutation in each of the p16 and p15 genes was observed in ten metastatic lesions. Eight (18.2%) replication errors were detected in three microsatellite loci in the primary melanoma samples, but no replication error was detected in the metastatic samples. None of the samples showed the alteration of p16/p15 genes and the replication errors concomitantly. These results suggest that (1) the homozygous deletions of p16/p15 genes and the replication errors may occur in rather early stages of melanoma tumorigenesis, while the p16/p15 gene mutation may occur in later stages, and (2) the p16 and p15 gene mutations in sporadic malignant melanomas might not be induced by the defect in mismatch repair, implying that p16 as well as p15 gene alterations may play an important role in the pathogenesis of sporadic malignant melanomas.

Adenine Nucleotides↗
PubMed1998

Complete restoration of normal DNA repair characteristics in group F xeroderma pigmentosum cells by over-expression of transfected XPF cDNA.

XP-F cDNA was cloned into a mammalian expression vector plasmid, and introduced into group F xeroderma pigmentosum (XP-F) cells. Several cell clones possessing transfected XPF cDNA were randomly isolated, and DNA repair characteristics of a clone, XP-FR2, were extensively analyzed. The XP-FR2 cells expressed high level of XPF protein as well as ERCC1 protein, although their parental XP-F cells expressed extremely low level of both proteins. The XP-FR2 cells showed UV resistance comparable to normal human cells, and had normal levels of UV-induced unscheduled DNA synthesis and normal capability to remove cyclobutane pyrimidine dimers and (6-4) photoproducts. Frequencies and types of UV-induced mutations examined by shuttle vector plasmids in XP-FR2 cells were similar to those in normal human cells. These results demonstrate that excision repair defect in XP-F cells is fully corrected by over-expression of XPF cDNA alone, although only partial correction of the cells by XPF cDNA has been reported before.

Base Sequence↗
PubMed1998

Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms.

Xeroderma pigmentosum (XP) complementation group F was first reported in Japan and most XP-F patients reported to date are Japanese. The clinical features of XP-F patients are rather mild, including late onset of skin cancer. Recently a cDNA that corrects the repair deficiency of cultured XP-F cells was isolated. The XPF protein forms a tight complex with ERCC1 and this complex functions as a structure-specific endonuclease responsible for the 5' incision during DNA excision repair. Here we have identified XPF mRNA mutations and examined levels of the mRNA and protein expression in seven primary cell strains from Japanese XP-F patients. The XP-F cell strains were classified into three types in terms of the effect of the mutation on the predicted protein; (i) XPF proteins with amino acid substitutions; (ii) amino acid substituted and truncated XPF proteins; and (iii) truncated XPF protein only. A normal level of expression of XPF mRNA was observed in XP-F cells but XPF protein was extremely low. These results indicate that the detected mutations lead to unstable XPF protein, resulting in a decrease in formation of the ERCC1-XPF endonuclease complex. Slow excision repair of UV-induced DNA damage due to low residual endonuclease activity provides a plausible explanation for the typical mild phenotype of XP-F patients.

Adult↗
PubMed1997

Werner's syndrome--chromosome analyses of cultured fibroblasts and mitogen-stimulated lymphocytes.

Two cases of Werner's syndrome are reported. Fibroblasts derived from both patients revealed reduced population doubling numbers. Chromosomal analyses for fibroblasts from both patients and lymphocytes from one patient revealed that chromosomal aberrations occur frequently and randomly. Although some of the chromosomal aberrations involved sites where tumour suppressor genes have been mapped, neither of our patients demonstrated malignancy. Chromosomal aberration at one critical site may not be sufficient to induce cancer or additional factors may be necessary.

Cell Culture Techniques↗