Novel compound heterozygous mutations in the cytochrome P4501B1 gene (CYP1B1) in a Japanese patient with primary congenital glaucoma

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder characterized by a rapid bilateral loss of central vision. The majority of patients have one of three mutations in the mitochondrial DNA. In order to identify the genetic cause of the disease in a family with two affected individuals without any of the three primary LHON mutations, we have sequenced the complete mitochondrial genome. Sequence analysis revealed a point mutation at position 14568 in the mitochondrial ND6 gene that changes a conserved methionine residue to isoleucine. This mutation has been previously suggested to be of pathogenic significance and has not been detected in any controls. This case confirms the pathogenicity of this mutation. It is the seventh mutation in the ND6 gene leading to LHON. All seven identified mutations in the ND6 gene lie within the evolutionarily most conserved region of the ND6 gene in a hydrophobic pocket making it a hot spot for the disease. This clustering of mutations may help to understand the disease mechanism of LHON.     

Successful transvaginal repair of a rectovaginal fistula developing after double-stapled anastomosis in low anterior resection: Report of four cases

(Received for publication on Dec. 8, 1997; accepted on Sept. 11, 1998)     

Expression of Heat Shock Protein 70 in Rabbit Liver After Contrast-Enhanced Ultrasound and Radiofrequency Ablation

Heat shock proteins (HSPs) induced by thermal ablation therapy may help presenting tumor antigen to the host immune system and be a valuable adjuvant in the ablation therapy of liver cancer. This paper described our preliminary study on the expression of HSP70 in rabbit liver after contrast-enhanced ultrasound (CEUS) and radiofrequency (RF) ablation. Twenty-five male New Zealand white rabbits were divided into five groups as: control group (n=5), ultrasound group (n=5), CEUS group (n=5), RF group (n=5) and CEUS + RF group (n=5). Clinical ultrasound and RF ablation equipment were used in the present experiment. Sonazoid was used as the contrast agent. All the animals were sacrificed 24 h after the procedure, and HSP70 was detected by immunohistochemistry staining and Western blot analysis. In the groups without RF ablation, there was no evidence of HSP70 expression in the liver tissue of the control group and ultrasound group, whereas positive HSP70 expression was detected in the liver tissue of the CEUS group, with a mean optical density of 0.33. In the RF and CEUS + RF groups, there were cells showing HSP70 expression in the normal liver tissue far from the ablation region. The mean densities of HSP70 expression were 0.31 in the RF group and 0.35 in the CEUS + RF group, respectively. With regard to the distribution of HSP70 expression of the RF and CEUS + RF groups, the marginal areas were stronger than liver tissue 1 cm away from the margin, and the ablated tissues showed no evidence of HSP70 expression. The mean density of HSP70 expression in the marginal areas were 0.47 in the RF group and 0.42 in the CEUS + RF group, respectively. CEUS using Sonazoid may produce HSP70 expression in the normal liver parenchyma after CEUS examination and RF ablation. (E-mail: moriyasu@tokyo-med.ac.jp)     

Pharmacokinetic and clinical studies of cefodizime in the field of obstetrics and gynecology

Cefodizime (THR-221, CDZM), a new antibiotic, was studied pharmacokinetically and clinically. The results obtained are summarized as follows: 1. Concentrations of CDZM in internal genital tissues were quite high after an intravenous infusion. 2. Clinical effects of the therapy with CDZM using intravenous infusion twice daily were evaluated in 1 patient with endometritis, 2 patients with pyometra, 1 patient with extragenital abscess and 1 patient with BARTHOLIN'S gland abscess. Clinical responses were good in all 5 patients. No side effects nor abnormal laboratory test values due to the drug were noted.     

Computed tomography of the TMJ in diagnosis of ankylosis: two case reports

Ankylosis of the temporomandibular joint is characterized by restriction or limitation of mandibular movement. It presents as a classic symptom a limited range of motion on opening. Radiographically, ankylosis presents features that facilitate the diagnosis. However, its visualization is not clear in most of the cases involving conventional radiographic techniques. With the evolution of radiographic techniques, computed tomography (CT) became an important examination in the diagnosis of the ankylosis of temporomandibular joint. Due to the increasing use of the CT and its importance in the diagnosis of this disease, the aim of this paper is to present and describe tomographic images of ankylosis of this joint by presenting two clinical cases, using several slices as axial, coronal, and three-dimensional reformatted images.     

Combination chemotherapy with weekly paclitaxel or docetaxel, carboplatin, and estramustine for hormone-refractory prostate cancer

Paclitaxel (PTX) and docetaxel (DTX) have been reported to be effective for treating hormone-refractory prostate cancer (HRPC). The objective of this study was to examine the efficacy of weekly DTX (PTX)-based chemotherapy and compare weekly DTX-based chemotherapy with triweekly (once every 3 weeks) DTX-based chemotherapy. We performed a combination chemotherapy on a weekly cycle with an i.v. PTX 100 mg/m² or i.v. DTX 30 mg/m² (days 1, 8, 15, and 22), i.v. carboplatin (CBDCA) (day 1, area under the plasma concentration time curve = 6), and oral estramustine phosphate 10 mg/kg daily for 10 HRPC patients. In addition, we investigated the patient characteristics and treatment efficacy and toxicity. Among all cases, serum prostate-specific antigen (PSA) decreased by 50% or more in 90% of patients, by 75% or more in 70%, and 90% or more in 40% after chemotherapy. The effectiveness of weekly DTX-based chemotherapy was comparable with previous reports, and we showed no toxicity serious enough to require cancellation of chemotherapy. In conclusion, weekly DTX-based chemotherapy was no less effective and less toxic than triweekly DTX-based chemotherapy for HRPC patients and therefore can be useful as the first-line chemotherapy regimen for HRPC patients, especially the elderly or those with a poor performance status.     

Dynamics of mitochondria during the cell cycle

Mitochondria are highly dynamic organelles in eukaryotic cells. Although the role of mitochondria in metabolism, ATP production and apoptosis is more widely recognized, alterations in mitochondrial morphology and abundance are also important for cellular functions. Here we investigated mitochondrial dynamics in synchronized HeLa cells in which the major stages of the cell cycle of the observed cells were resolved by staining phosphorylate histones H1 and H3, and showed that mitochondria exist as filamentous network structures throughout the cell cycle progression, changing their morphology, distribution, and abundance. The current results suggest that mitochondrial condensation occurred at prophase is required for the proper progression of mitochondrial division.     

Chemical constituents from the peels of Citrus sudachi

A methanol extract of the peels of Citrus sudachi gave five new compounds (1-5) and 27 known compounds. The structures were elucidated on the basis of spectroscopic evidence. Several of these compounds were assayed for antimicrobial activity against methicillin-resistant Staphylococcus aureus and Helicobacter pylori, and sudachitin (6) and 3'-demethoxysudachitin (7) were the most active.     

Long-term efficacy and safety of combined topical antiglaucoma therapy--timolol & unoprostone vs. betaxolol & unoprostone

PURPOSE: To evaluate long-term efficacy and safety of treatment combining topical beta-blockers and isopropyl unoprostone in primary open-angle glaucoma and normal-tension glaucoma patients. METHODS: A prospective, open-label, parallel-group clinical comparison trial was performed to evaluate efficacy and safety of treatment combining 0.5% betaxolol and 0.12% isopropyl unoprostone (B&U) or 0.5% timolol and 0.12% isopropyl unoprostone (T&U). Forty eyes of 40 patients, which were matched in the aging and the stage of glaucomatous visual field defect, were studied. Twenty patients were treated with B&U and the other twenty patients with T&U twice daily for 24 months. Goldmann intraocular pressure(IOP), Humphrey automated perimetry, blood pressure, heart rate, and peak flow were done every six months in each group. RESULTS: In the B&U treatment group, mean IOP was 21.2 mmHg at baseline and 18.3 mmHg(p < 0.005) after 2 years, and in the T&U treatment group it was 21.1 mmHg at baseline and 17.9 mmHg (p < 0.001) after 2 years. The cases in which MD value decreased over 2 dB were one in the B&U treatment group and three in the T&U treatment group. The average MD value was significantly improved from -7.40 dB to -5.90 dB after 2 years with B&U treatment(p < 0.05), but there was no difference with the T&U treatment. None of the patients stopped combined therapy because of side effects, though heart rate was significantly reduced only in T&U treatment group. CONCLUSION: Both combined treatments were effective for IOP reduction in glaucoma patients, and the data from the B&U treatment group suggested that B&U was more effective in maintaining visual field than T&U.