Biomedical subjects

S Horiki

Publications and source records attributed to S Horiki.

9 recordsLinked to original sources

PubMed2001

Photobiologic and photoimmunologic characteristics of XPA gene-deficient mice.

Xeroderma pigmentosum group A (XPA) gene-deficient mice cannot repair UV-induced DNA damage and easily develop skin cancers by UV irradiation. Just like human XP patients, homozygous (-/-) mice developed stronger longer-lasting acute inflammation than did wild-type mice after a single irradiation with UVB. Moreover, the model mice showed more severe UV-induced damage of keratinocytes and Langerhans cells than did the control mice. UVB-induced local and systemic immunosuppression was greatly enhanced in the (-/-) mice. Treatment with indomethacin, an inhibitor of prostaglandin (PG) synthesis, inhibited UV-induced inflammation and abrogated immunosuppression. In XPA-deficient mice, the amount of PGE2 and the expression level of COX-2 mRNA greatly increased after UVB irradiation compared with wild-type mice. These results suggest that the excess DNA photoproducts remaining in XPA-deficient cells after UV radiation induce COX-2 expression and subsequently produce a high amount of PGE2, which causes the enhancement of inflammation and immunosuppression. In XPA-deficient mice, the natural killer cell activity significantly decreased after repeated exposures to UVB. Our experimental data indicate that cancer development in XP patients involves not only mutagenesis due to the defect in DNA repair, but also the enhanced UV-immunosuppression and intensified impairment of natural killer function.

Animals↗

PubMed2000

Protective effects of sunscreening agents on photocarcinogenesis, photoaging, and DNA damage in XPA gene knockout mice.

We investigated the protective effects of commercial sunscreening agents against UVB-induced photoresponses in group A xeroderma pigmentosum (XPA) model mice. XPA gene-deficient mice are defective in nucleotide excision repair and show a high incidence of skin tumors and severe acute inflammation in response to UVB irradiation, in a similar manner to XP patients. SPF 10 and SPF 60 sunscreens protected partially and almost completely, respectively, ear swelling responses produced by UVB up to 200 mJ/cm2 in (-/-) mice. XPA (-/-) mice were irradiated three times a week to a cumulative dose of 2.6 J/cm2 UVB for a period of 24 weeks with or without SPF 10 or SPF 60 sunscreen. UV-induced skin tumors had developed in all unprotected (-/-) mice (13.3 tumors per mouse) at the completion of UVB irradiation. The SPF 60 sunscreen afforded stronger protection against photocarcinogenesis (1.0 tumors per mouse) than the SPF 10 sunscreen (4.4 tumors per mouse). Regarding photoaging, SPF 60 sunscreen also protected against mast cell infiltration (79% inhibition), elastic fiber accumulation, and dermal cyst proliferation in XPA (-/-) mice compared with unprotected (-/-) mice. In (-/-) mice, the SPF 60 sunscreen provided stronger protection against cyclobutane pyrimidine dimer formation shown immunohistologically following irradiation with 200 mJ/cm2 UVB than the SPF 10 sunscreen. The XPA model mouse is a useful animal for the evaluation of the photoprotective ability of sunscreens because photoresponses, even chronic changes, can be easily and quickly induced experimentally.

Aging↗

PubMed2000

Gallbladder agenesis with no other biliary tract abnormality: report of a case and review of the literature.

We report a rare adult case of gallbladder agenesis with no other biliary tract abnormality. The patient was a 29-year-old man with pain in the right upper-quadrant of the abdomen, and vomiting. The gallbladder was not visualized by ultrasonography, computed tomography, or endoscopic retrograde cholangiography. The common bile duct was slightly dilated. No other abnormalities, including anomalous choledochopancreatic duct junction, were found. Based on these imaging findings and the patient's right hypochondrial pain, there was a high index of suspicion of chronic cholecystitis caused by incarcerated gallstones in the neck of the gallbladder. At operation, we carefully observed the gallbladder fossa, using laparoscopy, and found gallbladder to be absent. Although the operation involved only observation via a laparoscope, the patient has since remained well and asymptomatic. It is difficult to make a correct diagnosis of gallbladder agenesis preoperatively. We believe that, if the gallbladder is not visualized by imaging techniques, it may be better to perform laparoscopy for observation before performing laparotomy, in order to reduce surgical stress.

Adult↗

PubMed2000

Acute appendicitis caused by amebiasis.

We report a case of appendicitis caused by amebiasis in a 45-year-old Japanese man. He presented to our hospital with bloody stools in June 1998. Sigmoidoscopy disclosed erosion, and a biopsy of the erosion showed colitis caused by Entamoeba histolytica infection. Four months later, he was admitted to our hospital with a small elastic mass and severe pain in the lower quadrant of the abdomen, which was diagnosed as acute appendicitis. He underwent appendectomy. Histopathological examination revealed numerous E. histolytica trophozoites, and we diagnosed acute appendicitis caused by E. histolytica. The patient has been free of symptoms, colonoscopy has revealed no erosion, and biopsy has revealed no E. histolytica for 12 months after the operation.

Appendicitis↗

PubMed1998

Can POSSUM, a scoring system for perioperative surgical risk, predict postoperative clinical course?

POSSUM, a Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity, is a scoring system which assesses perioperative surgical risks (Copeland GP et al.: Br J Surg, 1991, Vol 78, 356-360). The POSSUM scoring system consists of two categories of assessment to assess the risk of surgery. A 12-factor (age, cardiac status, pulse rate, systolic blood pressure, respiratory status, Glasgow Coma Score, serum concentration of urea, potassium and sodium, hemoglobin concentration, white cell count and findings on electrocardiography) and 4-grade physiological score (PS) were developed. This was combined with a 6-factor (type of surgical procedure, number of procedures, blood loss, peritoneal soiling, presence of malignancy and mode of surgery) and 4-grade operative severity score (OSS). The present paper attempts to validate it retrospectively. Postoperative hospitalization period and duration of antibiotics administration were both significantly correlated with OSS, but not with PS. These results suggest that the POSSUM scoring system is useful for predicting the postoperative clinical course.

Adult↗

PubMed1994

Clinical and experimental photosensitivity reaction to tilisolol hydrochloride.

This report describes a patient who developed a photosensitivity reaction during the treatment of hypertension with tilisolol hydrochloride, which is a beta-blocker agent Although the data are insufficient to distinguish photoallergy and phototoxicity, clinical and histologic features suggested that the mechanism involved was photoallergic in nature. The action spectrum was mainly the ultraviolet A range. The reaction was reproducible on oral readministration of the drug and exposure to a low dose of UVA. Photopatch testing with the drug was also positive only in the patient. Although the experimental photoallergic reaction was not induced in the guinea pig, phototoxic potential was demonstrated in the animal. To our knowledge, a photosensitivity reaction due to tilisolol hydrochloride has not been previously reported in the English literature.

Adrenergic beta-Antagonists↗

PubMed1992

Flow cytometric analysis on perforin induction in peripheral blood mononuclear cells with interleukin-2 or OK-432.

Perforin is a protein present in the cytoplasmic granules of killer cells and is considered to be an important effector molecule. We assessed the perforin appearance via flow cytometry in human peripheral blood mononuclear cells stimulated in vitro for 3 days by recombinant interleukin-2 (rIL-2) or OK-432, a biological response modifier. The relationship between the lymphocyte subsets and perforin was investigated via two-color assay. CD4-positive cells had almost no perforin, and most of the CD16-positive cells did. Regarding the relationship with CD8, some of the bright positive cells (which were likely T cells) and most of the dull positive cells (likely NK cells) had perforin. Mean fluorescence was greatest in perforin-positive cells incubated with rIL-2, less in cells incubated with OK-432, and minimal in cells incubated in a medium without additives. Immunohistochemical staining with antiperforin antibody revealed that blast-transformed and enlarge cells were stained positively and that the intensity of staining of each cell alone was enhanced in cells incubated with OK-432 or rIL-2. If the fluorescence intensity of perforin-positive cells correlates with the amount of perforin in those cells, then the appearance of perforin was enhanced with OK-432, more enhanced with rIL-2, and consistent for cytotoxicity against K562 and Daudi cells. IL-2 was induced by OK-432, suggesting that the indirect effect of this IL-2 may play a role in OK-432-perforin induction. The results suggest that perforin may be an effector molecule in killer cells induced by rIL-2 or OK-432.

Cytotoxicity, Immunologic↗

PubMed1992

[Antitumor effect of pirarubicin (THP) against human colon cancer transplanted into nude mice and the mechanism of cell cycle progression].

Pirarubicin (THP) is a derivative of adriamycin (ADM) which has been reported to have a lower cardiotoxicity than ADM. The authors investigated the in vivo antitumor effect of THP against human colon cancer cells (RPMI 4788) xenografted into nude mice. In the model of intra-abdominal carcinomatosis, intraperitoneal administration of THP (6 mg/kg) resulted in a significant prolongation of the survival compared with the saline control group (p less than 0.01). Intravenous administration of THP (8 mg/kg) significantly inhibited tumor growth compared with the saline control group. Labeling index with bromodeoxyuridine (BrdU) of RPMI 4788 tumors treated with THP was smaller than that in the control group. Mitotic index was also smaller in the group treated with THP. Labeling index with BrdU indicates the proportion of cells in the S phase. Thus, the tumor cells in both S and M phases have decreased after treatment with THP. This change in the cell cycle progression may be due to the accumulation of G2 phase similar to in vitro study. From these results, it was suggested that the change in cell cycle progression revealed in vitro might be caused by THP in vivo.

Animals↗

PubMedDate not supplied

In vivo augmentation of the intratumoral concentration of 5-fluorouracil by cepharanthine--a biscoclaurine alkaloid.

We have investigated the interaction between Cepharanthine (CEP), a multi-functional alkaloid that has the capacity to stabilize the cell membrane, and 5-fluorouracil (5-FU) against a human colon cancer cell line (RPMI 4788) transplanted into nude mice. Their anti-tumor effects were assessed in a group of 7 mice intravenously injected with CEP (5 mg/kg/day) and/or 5-FU (15 mg/kg/day) during a 3-week treatment. The results were compared with a control and a 5-FU group, which received saline solution and 5-FU alone, respectively. The tumors were harvested 2 h after 5-FU administration. On an additional 4 groups of 5 mice, the intratumoral concentration of 5-FU was assessed by a high performance liquid chromatographic (HPLC) method 2, 4, 6 and 12 h following CEP (5 mg/kg) injection 1 h prior to, simultaneously, and 1 h after injection of 5-FU (30 mg/kg). The mean (SD) intratumoral concentration of 5-FU was 0.16 (0.05) mu g/g, 0.32 (0.19) mu g/g, 0.32 (0.16) mu g/g and 0.21 (0.13) mu g/g in the control and the three other groups treated with CEP, respectively. This concentration was about twice as high in mice simultaneously treated with CEP compared to those treated by 5-FU alone. Relatively higher concentrations of 5-FU were noted up to 4 h following 5-FU injection in mice treated with CEP than in those injected only with 5-FU. CEP also enhanced the inhibitory effects of the 5-FU on tumor growth rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗