Increased in vitro release of interferon-gamma from ampicillin-stimulated peripheral blood mononuclear cells in Stevens-Johnson syndrome

Stevens-Johnson syndrome (SJS) was diagnosed in a 39-year-old woman, treated with ampicillin (4000-8000 mg daily), phenytoin (250 mg daily), and furosemide (20-40 mg daily) for 25, 21, and 20 d, respectively, before the appearance of the eruption. The lymphocyte stimulation test with the MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay on ampicillin, phenytoin, and furosemide showed a low value of stimulation index, which indicated negative reactivity. An in vitro IFN-gamma release test was conducted on the patient with SJS and on two healthy controls. IFN-gamma release increased by 52% following the in vitro challenge of the patient's peripheral blood mononuclear cells (PBMCs) with 15 microg/ml of ampicillin, but not with phenytoin or furosemide. Neither of the controls experienced increased IFN-gamma release. In the present case, increased in vitro IFN-gamma release was observed on ampicillin-stimulated PBMCs, which may indicate the role of ampicillin as the drug responsible for the induction of SJS, and may imply the role of IFN-gamma in the pathogenesis of SJS.     

Suppressive effect of Kanzo-bushi-to, a Kampo medicine, on collagen-induced arthritis

Kanzo-bushi-to (KBT) is a traditional Japanese herbal medicine (Kampo medicine), which is used in Japan to treat rheumatoid arthritis. In the present study, we investigated the suppressive effect of KBT on collagen-induced arthritis (CIA) and further studied the underlying mechanism. CIA was induced in male DBA/1J mice by immunization with bovine type II collagen, followed by a booster injection 21 d later. KBT was given at a dose of 430 mg/kg/d from three days before the first immunization to the end of the experiment. KBT suppressed CIA development effectively and further protected focal bone erosion and bone destruction as evidenced by the reduced histological score. Histochemical examination revealed that KBT decreased TRAP-positive cells at the synovium-bone interface and at the sites of focal bone erosion, coincident with the findings that RANKL/OPG mRNA ratio was significantly reduced by KBT treatment. KBT also decreased mRNA levels of M-CSF and iNOS in joints and of iNOS in peritoneal macrophages. In conclusion, KBT prevented osteoclast generation by decreasing RANKL/OPG ratio and M-CSF mRNA levels, resulting in reduction in bone erosion and destruction. In addition, KBT has anti-inflammatory effect such as the suppression of iNOS expression in peritoneal macrophages and joints of CIA mice. These finding suggests that KBT is a potential new therapeutic agent for the treatment of RA.     

Postoperative results of non-penetrating trabeculectomy for primary open-angle glaucoma

PURPOSE: To estimate the postoperative results of non-penetrating trabeculectomy(NPT), the success rate of postoperative intraocular pressure(IOP) and the clinical factors affecting postoperative IOP were evaluated. SUBJECTS AND METHODS: 32 eyes of 32 primary open-angle glaucoma(POAG) patients who underwent NPT as the first filtering surgery were enrolled in the study. We evaluated postoperative IOP using the Kaplan-Meier method, a proportional hazard model, and multiple logistic analysis. RESULTS: 53.2% of all patients had an IOP of less than 16 mmHg without antiglaucoma medication, and 63.8% had an IOP of less than 16 mmHg with antiglaucoma medication 36 months postoperatively. The performance of Nd:YAG trabeculopuncture(YLT) was indicated as a significant factor affecting postoperative IOP by the proportional hazard model(p = 0.037). 72.2% of patients who did not undergo YLT had an IOP of less than 16 mmHg without antiglaucoma medication, and 36.5% who underwent YLT had a postoperative IOP of less than 16 mmHg. There was significant difference between the both groups(log rank test, p = 0.045). Preoperative IOP with antiglaucoma medication was indicated as a significant factor affecting performance of YLT by multiple logistic analysis. CONCLUSION: These results suggest that NPT may be useful to reduce the use of antiglaucoma medication in patients with POAG whose preoperative IOP is controllable with antiglaucoma medication.     

Intravitreal injection of triamcinolone acetonide for cystoid macular edema resistant to vitreous surgery

PURPOSE: To report the efficacy of intravitreal injection of triamcinolone acetonide(TA) for cystoid macular edema remaining after vitreous surgery. METHODS: Eight eyes of 7 patients aged from 32 to 84 years old were studied. The original diseases that caused macular edema were central retinal vein occlusion in 2 eyes, branch retinal vein occlusion in one eye, Irvine-Gass syndrome in 2 eyes, and diabetic retinopathy in 3 eyes. 4 mg of TA was injected intravitreally and visual acuity and foveal thickness measured by optical coherence tomography(OCT) were evaluated in before and after the surgery. RESULTS: Macular edema resolved rapidly after injection of TA in all cases and cysts were extinguished or diminished. The foveal thickness in OCT was reduced significantly from preoperative 495 +/- 116 (mean +/- standard deviation) microns to 267 +/- 117 microns after one week, and 246 +/- 81 microns after one month. The effect persisted for three months. Visual improvement of more than two Snellen lines was seen in 4 eyes. No side effects were observed except a temporary increase of intraocular pressure in one eye. CONCLUSION: Intravitreal injection of TA is effective in a short-term for cystoid macular edema remaining after vitrectomy.     

Tissue-specific regulation of 4E-BP1 and S6K1 phosphorylation by alpha-ketoisocaproate

The indispensable branched-chain amino acid leucine acts as a key regulator of mRNA translation by modulating the phosphorylation of proteins that represent important control points in translation initiation, including the translational repressor, eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (S6K1). In the current study, we compared the effects of L- and D-enantiomers of leucine on the phosphorylation of 4E-BP1 and S6K1. We also assessed whether leucine itself or its metabolite, alpha-ketoisocaproate (alpha-KIC), mediates the effects of leucine. Food-deprived (18 h) rats were orally administered 135 mg/100 g body weight L-leucine, D-leucine or alpha-KIC and were sacrificed after 1 h. L-Leucine administration had an obvious stimulatory effect on the phosphorylation of 4E-BP1 and S6K1 in both skeletal muscle and liver while D-leucine was much less effective, indicating that the effect of leucine is stereospecific. Oral administration of alpha-KIC mimicked the stimulatory effect of L-leucine in skeletal muscle. In contrast to skeletal muscle, provision of alpha-KIC was significantly less effective than L-leucine in the liver. The results showing that the efficacy of L-leucine and alpha-KIC in stimulating phosphorylation of S6K1 and 4E-BP1 is equivalent in skeletal muscle, may be explained by the conversion of alpha-KIC to L-leucine.     

A case of chondromatous tumor of the breast

This report describes an exceedingly rare case of a benign cartilage-containing breast tumor that developed in the right breast of a 52-year-old woman. She found the mass on self examination. Physical examination revealed a 1.5 x 1.4 cm, firm, smooth and mobile lump in the lower medial quadrant close to the nipple of the right breast. Mammography revealed a slightly indistinct margined, oval-shaped, and high density nodule without microcalcifications. On ultrasonography, the lesion was a hypoechoic, oval-shaped mass with an echogenic spot. The border was slightly rough. Fine needle aspiration cytology revealed some giant cells and necrotic tissue. Excisional biopsy was then performed. Histopathologically, the lesion consisted of islands of mature hyaline cartilage with intervening strands of fibrous stroma. Mammary lobules and ducts were lacking within the mass. Fat and muscular components were not present. Therefore chondromatous tumor of the breast was diagnosed.     

Complete response to irinotecan hydrochloride and nedaplatin in a patient with advanced ovarian clear cell carcinoma

A 55-year-old multiparous woman was diagnosed with stage IIIc ovarian clear cell carcinoma. Three years after the first surgery and adjuvant chemotherapy with irinotecan hydrochloride and mitomycin C, she developed common iliac lymph node recurrence. Two cycles of chemotherapy with irinotecan hydrochloride and nedaplatin led to a complete response. Surgical resection revealed pathological complete response. The chemosensitivity of ovarian clear cell carcinoma has been reported to be very poor. No standard chemotherapeutic regimens for this carcinoma have been established. The present study is the first report of a pathological complete response in a patient with advanced ovarian clear cell carcinoma. Future studies are needed to confirm the efficacy of this regimen for this carcinoma.     

Suppression of VEGFR-3 signaling inhibits lymph node metastasis in gastric cancer

In gastric cancer, lymph node metastasis is one of the major prognostic factors and forms the basis for surgical removal of local lymph nodes. Recently, several studies have demonstrated that overexpression of lymphangiogenic growth factor VEGF-C or VEGF-D induces tumor lymphangiogenesis and promotes lymphatic metastasis in mouse tumor models. We examined whether these processes could be inhibited in naturally metastatic tumors by blocking of their cognate receptor VEGFR-3 signaling pathway. Using a mouse orthotopic gastric cancer model which has a high frequency of lymph node metastasis, we estimated lymphatic vessels in gastric cancers by immunostaining for VEGFR-3 and other specific lymphatic markers, LYVE-1 and prox-1. Then we systemically administered anti-VEGFR-3 blocking antibodies. This treatment resulted in the inhibition of regional lymph node metastasis and reduction of lymphatic vessel density in the primary tumors. In addition, increased density of LYVE-1-positive lymphatic vessels of primary tumors was closely correlated with lymph node metastasis in human samples of gastric cancer. Antilymphangiogenesis by inhibiting VEGFR-3 signaling could provide a potential strategy for the prevention of lymph node metastasis in gastric cancer.