ISCEV and IPS guideline for the full-field stimulus test (FST).

The full-field stimulus test (FST) is a psychophysical technique designed for the measurement of visual function in low vision. The method involves the use of a ganzfeld stimulator, as used in routine full-field electroretinography, to deliver full-field flashes of light. This guideline was developed jointly by the International Society for Clinical Electrophysiology of Vision (ISCEV) and Imaging and Perimetry Society (IPS) in order to provide technical information, promote consistency of testing and reporting, and encourage convergence of methods for FST. It is intended to aid practitioners and guide the formulation of FST protocols, with a view to future standardisation.

Electro-optic probe measurements of electric fields in plasmas.

The direct measurements of high-frequency electric fields in a plasma bring about significant advances in the physics and engineering of various waves. We have developed an electro-optic sensor system based on the Pockels effect. Since the signal is transmitted through an optical fiber, the system has high tolerance for electromagnetic noises. To demonstrate its applicability to plasma experiments, we report the first result of measurement of the ion-cyclotron wave excited in the RT-1 magnetosphere device. This study compares the results of experimental field measurements with simulation results of electric fields in plasmas.

Introduction of formal debate into a postgraduate specialty track education programme in periodontics in Japan.

AIM: To evaluate the formal debate as an active learning strategy within a postgraduate specialty track education programme in periodontics. METHODS: A formal debate was implemented as an active learning strategy in the programme. The participants were full-time faculty, residents and dentists attending special courses at a teaching hospital in Japan. They were grouped into two evenly matched opposing teams, judges and audience. As a preparation for the debate, the participants attended a lecture on critical thinking. At the time of debate, each team provided a theme report with a list of references. Performances and contents of the debate were evaluated by the course instructors and audience. Pre- and post-debate testing was used to assess the participants' objective knowledge on clinical periodontology. RESULTS: Evaluation of the debate by the participants revealed that scores for criteria, such as presentation performance, response with logic and rebuttal effectiveness were relatively low. Thirty-eight per cent of the participants demonstrated higher test scores after the debate, although there was no statistically significant difference in the mean scores between pre- and post-tests. At the end of the debate, vast majority of participants recognised the significance and importance of the formal debate in the programme. CONCLUSION: It was suggested that the incorporation of the formal debate could serve as an educational tool for the postgraduate specialty track programme.

Fluorescence in situ hybridization evaluation of c-erbB-2 gene amplification and chromosomal anomalies in bladder cancer.

Oncogene amplification and chromosomal anomalies are found in many solid tumors and are often associated with aggressiveness of cancer. We evaluated the frequency and the role of c-erbB-2 gene amplification, relative increase in c-erbB-2 gene copy number, and gain of chromosome 17 in bladder cancer. A total of 29 bladder cancer specimens were examined using fluorescence in situ hybridization (FISH). Dual labeling hybridization with a directly labeled centromere probe for chromosome 17 together with a probe for the c-erbB-2 locus was performed. c-erbB-2 gene amplification was found in 3.4% (1 of 29) of specimens. Relative increase in c-erbB-2 gene copy number was found in 41.4% (12 of 29) of specimens and was significantly associated with tumor grade (P = 0.044 by Fisher's exact test). Gain of chromosome 17 was identified in 65.5% (19 of 29) of specimens and was significantly associated with tumor grade (P = 0.002 by Fisher's exact test) and tumor stage (P = 0.003 by Fisher's exact test). Our results suggest that c-erbB-2 gene amplification, relative increase in c-erbB-2 gene copy number, and gain of chromosome 17 may play important roles in the development and progression of bladder cancers. Moreover, the use of c-erbB-2 amplification, relative increase in c-erbB-2 gene copy number, and gain of chromosome 17 using FISH, together with tumor grade and stage, may provide a more useful clinical indicator in bladder cancer.

[Diagnosis of prostate capsular invasion by pelvic magnetic resonance imaging and serum level of prostate specific antigen].

Transrectal ultrasonography (TRUS), computed tomography (CT), and magnetic resonance imaging (MRI) are employed to diagnose the clinical stage of prostate cancer. However, several cases are diagnosed as pathological stage pT3 after total prostatectomy. We investigated the accuracy of the evaluation of pathologic capsular penetration by preoperative pelvic MRI and preoperative serum PSA level and capsular penetration. The diagnostic accuracy of capsular penetration by MRI was 63.3%. On the other hand, the diagnostic accuracy of capsular penetration by preoperative PSA was 89.7% when its cut off value was 17 ng/ml. We conclude that preoperative serum PSA level could be more useful to diagnose accurately stage of prostate cancer than pelvic MRI.

Effect of F-1394, an acyl-CoA:cholesterol acyltransferase inhibitor, on atherosclerosis induced by high cholesterol diet in rabbits.

Cholesterol-fed rabbits were used to study the anti-atherosclerotic effect of (1S,2S)-2-[3-(2,2-dimethylpropyl)-3-nonylureido]cyclohexane-1-yl 3-[(4R)-N-(2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionate (F-1394), an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor. To test its effect on the development of atherosclerosis, rabbits were fed a high-cholesterol diet (HCD) for 6 weeks, followed by regular chow (RC) for 12 weeks plus 0 or 100 mg/kg per day F-1394. Serum total cholesterol (TC) rose to approximately 2000 mg/dl on HCD and then declined gradually after the change in diet in both groups. F-1394 significantly reduced the extent of the atherosclerotic lesions and the total and esterified cholesterol contents of the aorta (by 57,38, and 59%, respectively), without affecting the serum TC level. To clarify whether F-1394 accelerates the regression of preexisting atherosclerosis, rabbits were fed HCD for the first 6 weeks and then RC for the next 6 weeks. Then, the rabbits were given 0 or 100 x 2 mg/kg per day F-1394 for another 12 weeks while on RC. F-1394 significantly reduced the extent of the atherosclerotic lesions and the total and esterified cholesterol content in the aorta (by 31, 31, and 43%, respectively), without affecting the serum TC level. These results demonstrate that F-1394 both prevents the formation of atherosclerosis and accelerates its regression without affecting the serum TC level, indicating that F-1394 acts directly on the arterial wall.

Direct effect of an acyl-CoA:cholesterol acyltransferase inhibitor, F-1394, on atherosclerosis in apolipoprotein E and low density lipoprotein receptor double knockout mice.

The acyl-CoA:cholesterol acyltransferase (ACAT) enzyme is thought to be responsible for foam cell formation and the subsequent progression of atherosclerosis. The apolipoprotein E and low density lipoprotein receptor double knockout (apoE/LDLr-DKO) mouse is an animal model that develops severe hyperlipidaemia and atherosclerosis. Here we have examined the effect of oral administration of an ACAT inhibitor, F-1394, on atherosclerosis in apoE/LDLr-DKO mice fed a regular chow diet. In en face analysis, a dose of 10, 30, or 100 mg kg(-1) day(-1) F-1394 for 10 weeks reduced the extent of lesions visible in the aorta by 24, 28 and 38%, respectively, as detected by staining with oil red O, without affecting serum cholesterol level in these mice. At the highest dose 100 mg kg(-1) day(-1) of F-1394, the reduction was statistically significant. For quantitative analysis of the cellular and non-cellular components comprising the lesions at the aortic sinus, the effects of an oral dose of 100 mg kg(-1) day(-1) F-1394 for 15 weeks were studied. There was a significant reduction (31.9%) in the oil-red O-stained area in cross-sections of the aortic sinus. In addition, the neointimal area, as well as levels of ACAT-1 protein tended to be decreased (15.2 and 25.8%, respectively, not significant). However, the areas containing macrophages, smooth muscle cells, and collagen were not affected by F-1394. In vitro, F-1394 attenuated foam cell formation in mouse peritoneal macrophages. These results indicate that ACAT may be primarily responsible for lipid accumulation in atherosclerotic lesions, and that its inhibition diminishes the lipid deposition via a direct effect on macrophages in the arterial wall.

Postprandial hyperlipidemia in Zucker diabetic fatty fa/fa rats, an animal model of type II diabetes, and its amelioration by acyl-CoA:cholesterol acyltransferase inhibition.

Postprandial hyperlipidemia (PH) is frequently observed in diabetic patients. We performed an oral fat-loading test in Zucker diabetic fatty (ZDF) fa/fa rats, a model for type II diabetes, to determine whether PH was induced in the rats. Post fat-loading changes in serum cholesterol and triglyceride levels were significantly greater in the fa/fa rats than those seen in their lean littermates and an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor significantly reduced these levels by 24% and 31%, respectively. Therefore, we confirmed that PH appeared in ZDF fa/fa rats by fat loading and ACAT inhibition may be a potential treatment for PH.

[Clinicopathological study of influential factors on prognosis in patients with renal cell carcinoma].

Between January 1986 and August 1996, 120 patients were diagnosed with renal cell carcinoma (RCC) at Kanagawa Cancer Center. In this study, we analyzed these patients in view of the clinicopathological factors, which affect the prognosis of these patients with univariate and multivariate analysis using Cox's proportional hazard model. Of these 120 patients, 40 patients (33%) died of RCC during this period. The cause specific survival rate was 65% after 5 years and 57% after 10 years. Univariate analysis showed some factors, performance status, symptoms, tumor size, histological grade, local invasion (pT), venous involvement (pV), lung metastasis, lymph-node metastasis, and bone metastasis, affected the prognosis. Furthermore, multivariate analysis using Cox's proportional hazard model showed that performance status, pT, pV, lung metastasis, lymphnode metastasis, and bone metastasis independently affected the prognosis. In summary, TMN factors and performance status importantly affect the prognosis of RCC patients.

ACAT inhibitor F-1394 prevents intimal hyperplasia induced by balloon injury in rabbits.

Acyl-CoA:cholesterol acyltransferase (ACAT) is thought to contribute significantly to lipid deposition in macrophages, which subsequently leads to the initiation and progression of atherosclerosis. The aim of the present study was to examine the influence of hypercholesterolemia on arterial hyperplasia induced by endothelial denudation and the direct effect of ACAT inhibition on lesion formation. Rabbits were fed either a cholesterol diet or a regular diet for 4 weeks, and then the left common carotid arteries were denuded of endothelium. After the operation, all rabbits were kept on the regular diet for 2;-6 weeks. Two weeks after the denudation, the degree of intimal thickening and the number of proliferating cells (which were immunohistologically identified to be smooth muscle cells) were similar in hypercholesterolemic and normolipidemic rabbits. After that, both parameters progressively increased in hypercholesterolemic rabbits but declined in normolipidemic rabbits. Macrophages were apparent in the lesions only in hypercholesterolemic rabbits. Next, the effect of the ACAT inhibitor, (1S,2S)-2-[3-(2,2-dimethylpropyl)-3-nonylureido] cyclohexane-1-yl 3-[(4R)-N-(2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionate (F-1394), on neointimal formation in hypercholesterolemic rabbits was examined. Oral administration of F-1394 significantly reduced neointimal thickening and the extent of macrophages in lesions without affecting serum cholesterol levels. These results suggest that hypercholesterolemia causes macrophage-derived foam cell accumulation in lesions, and that the progression of lesions is accelerated by the presence of macrophages. Moreover, the study shows that F-1394 prevents neointimal formation even in the presence of hypercholesterolemia, indicating that F-1394 may be useful for treating restenosis after percutaneous translumenal coronary angioplasty in hyperlipidemic patients.

Fluorescence in situ hybridization evaluation of c-myc and androgen receptor gene amplification and chromosomal anomalies in prostate cancer in Japanese patients.

BACKGROUND: Oncogene amplification and chromosomal anomalies are found in many solid tumors and are often associated with aggressiveness of cancer. We evaluated the frequency and the association of c-myc and androgen receptor (AR) gene amplification and gain of chromosome 8 or X in prostate cancer in Japanese patients. METHODS: We examined a total of 42 prostate cancer specimens, using fluorescence in situ hybridization (FISH). Dual-labeling hybridization with a directly labeled centromere probe for chromosome 8 or X together with a probe for the c-myc or AR locus was performed. RESULTS: Gain of chromosome 8 was identified in 54.8% of specimens and was associated with Gleason sum and nuclear anaplasia in untreated prostate cancers. c-myc gene amplification was found in 14.3% of specimens. Gain of chromosome X was identified in 42.9% of specimens. AR gene amplification was detected in 0 of 37 untreated prostate cancers, but in 1 of 5 hormone-refractory prostate cancers. CONCLUSIONS: Our results suggest that c-myc and AR gene amplification and gain of chromosome 8 or X may be associated with the development and progression of prostate cancers. These results obtained in Japanese cases are consistent with the results observed in prostate cancer in Western countries.

Postprandial hyperlipidemia in streptozotocin-induced diabetic rats is due to abnormal increase in intestinal acyl coenzyme A:cholesterol acyltransferase activity.

Postprandial hyperlipidemia (PH) is recognized as a significant risk factor for cardiovascular disease. The present study, involving rats with streptozotocin (STZ)-induced diabetes, was performed to establish a PH model and to examine the relation between small intestinal acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity and serum lipid levels in the postprandial state. The small intestinal ACAT activities in normal rats during the experimental period were 4 to 5 pmol/mg protein per minute. In contrast, in the diabetic rats, the ACAT activities were 2 to 3 times higher than activities seen in normal rats from 7 to 21 days after the STZ injection in the absence of a high fat diet and hyperplasia in the gut. In an oral fat-loading test that used diabetic rats that had been injected with STZ (60 mg/kg) intravenously 14 days previously, the postloading changes in the serum concentrations of total cholesterol (TC) and triglyceride (TG) were significantly greater in the diabetic rats than in normal rats. Single oral administration of (1s,2s)-2-[3-(2,2-dimethylpropyl)-3-nonylureido]cyclohexane- 1-yl 3-[(4R)-N-(2,2,5,5-tetramethyl-1, 3-dioxane-4-carbonyl)amino]propionate (F-1394, 3 to 30 mg/kg), a potent ACAT inhibitor, suppressed the post-fat-loading elevation of serum TC levels in the diabetic rats in a dose-dependent manner without affecting serum glucose levels. Furthermore, the small intestinal ACAT activity, serum TG levels, and lymphatic absorption of TC and TG in the rats that were administered F-1394 (30 mg/kg) were reduced by approximately 90%, 70%, 30%, and 15%, respectively. This is the first evidence that elevated ACAT activity in the gut, unlike hyperplasia and hyperphagia, induces PH in rats. Our results strongly suggest that F-1394 may be a potential treatment for PH in humans.

[Combination chemotherapy with 5-FU and low-dose CDDP for urogenital tumors].

Chemotherapy with 5-FU and low-dose CDDP, MTX or LV has not been fully evaluated in urogenital tumors. In a study of advanced renal cell carcinoma, the response rate of the combination of 5-FU, CDDP and IFN-alpha was 9%. In urinary bladder cancer, the combination chemotherapy with 5-FU and low-dose CDDP has been used as a radiosensitizer. This combination chemotherapy with radiation introduced a high response rate and has been used for the preservation of bladder function with minimum invasive surgery. There are very few effective chemotherapies for advanced androgen independent prostate cancer. However, some oral fluoripyrimidine, like UFT, was shown to be effective to some extent for prostate cancer in a phase II study. Thus, combination therapies of 5-FU and low-dose CDDP for prostate cancer as a biochemical modulator may be expected.

[A case of advanced retroperitoneal dedifferentiated liposarcoma treated effectively with high-dose ifosfamide].

We report a case of retroperitoneal dedifferentiated liposarcoma treated effectively with high-dose ifosfamide. A 59-year-old man received tumorectomy and right nephrectomy for the retroperitoneal liposarcoma. Twenty-two months after the operation, the liver metastasis was resected incompletely. Three months later, right pleural, retroperitoneal and peritoneal metastases appeared. With 6 cycles of high-dose ifosfamide therapy these tumors were reduced partially. Ten cycles of this chemotherapy were administered. These tumors showed regrowth at 14 months after administration of high dose ifosfamide. The combination chemotherapy of ifosfamide and doxorubicine or etoposide was not effective after regrowth of the tumors.

[Long-term administration study of propiverine hydrochloride (BUP-4 tablets) in pollakiuria and urinary incontinence].

The safety and efficacy of one-year administration of propiverine hydrochloride (BUP-4 tablets) were assessed in facilities affiliated with the Department of Urology of Yokohama City University School of Medicine. Changes in subjective symptoms showed significant improvement in mean frequency of urination in the daytime from 10.3 +/- 4.0 times before administration to 7.1 +/- 2.9 times 1 year after the start of administration, in mean frequency of voiding at night from 4.2 +/- 1.7 times to 2.1 +/- 1.1 times and in mean incidence of urinary incontinence from 2.9 +/- 2.1 times to 0.7 +/- 1.0 times. The final degree of overall improvement rate was 82.0% (41/50 cases). Adverse effects were observed 26 times in 22 patients, the incidence being 15.6% (22/141 cases). They consisted of digestive symptoms in 9.9% (6 events of dry mouth, 4 of constipation, 2 of abdominal discomfort, 2 of diarrhea and 1 of gastritis), urinary tract symptoms in 3.5% (4 of dysuria and 1 of residual urine), abnormal laboratory findings in 1.4% (increase in glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase or lactate dehydrogenase levels) and others (1.4%). These results provide further evidence of the safety and efficacy of propiverine hydrochloride (BUP-4 tablets) even when administered for a long-term in the treatment of patients with pollakiuria and urinary incontinence.

Detection of telomerase activity in prostate needle-biopsy samples.

BACKGROUND: Telomerase in an enzyme ribonucleoprotein responsible for cell immortality and oncogenesis. Telomerase activity has been detected in most cancers, including prostate cancer. To verify whether the detection of telomerase in prostate needle biopsy samples could have diagnostic value, we blindly assayed telomerase activity in samples from patients who were clinically suspected of having prostate cancer. METHODS: A total of 183 prostate biopsy samples was obtained from 63 patients who were suspected of having prostate cancer. Telomerase activity was determined by polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay. An internal telomerase assay standard (ITAS) was used in this study to distinguish false negatives. RESULTS: Telomerase activity was detected in 17 of 19 (89.5%) patients with prostate cancer (chi(2) test, P < 0.005). In 39 of 42 (92.9%) biopsy samples from these 19 prostate cancer patients, confirmed histologically as prostate cancer, telomerase activity (chi(2) test, P < 0.005) was detected. Meanwhile, we also found one false-positive sample. In contrast, all of 44 normal or benign prostate disease patients (124 biopsy specimens) were telomerase-negative. We also revealed that poorly differentiated prostate cancer often expresses a high level of telomerase activity. The area of cancer tissue in biopsy specimens was not associated with relative telomerase activity. CONCLUSIONS: This study suggests that determination of telomerase activity in prostate needle-biopsy samples might be a useful tool for detecting prostate cancer.

[Prognostic significance of clinical stage including extent of disease (EOD) in prostate cancer].

We analyzed the prognostic significance of clinical stage using extent of disease (EOD) grading system in 288 patients with prostate cancer between 1970 and 1994. The cause-specific survival rate for EOD4 was significantly lower (p < 0.01) than that for the other EOD categories. On the other hand, the cause-specific survival rate for EOD1 was significantly higher (p < 0.01) than that of the other EOD categories, and moreover, it was similar to the cause-specific survival rates for stage C and D1. The cause-specific survival rate of EOD1 and poorly differentiated cases was higher than that of EOD2 or 3 and well or moderately differentiated cases until 2 years after treatment, but after 3 years, the cause-specific survival rate for EOD1 and poorly differentiated cases was lower than that for EOD2 or 3 and well or moderately differentiated cases. These findings suggest that the volume of cancer is associated with the prognosis of prostate cancer that failed in radical treatment and that in stage D2, histological grade is more closely associated with the prognosis after treatment for 3 years.

Telomerase activity in primary prostate cancer.

PURPOSE: Telomerase activity has been detected in a wide variety of human tumor types. We analyzed the telomerase activity in association with the acquisition of prostate cancer. MATERIALS AND METHODS: Telomerase activity in prostate tissues was examined by PCR-based telomeric repeat amplification protocol (TRAP) assay. RESULTS: Among 31 primary prostate cancers, 28 tissue samples (90%) displayed telomerase activity. The relative level of telomerase activity was associated with the pathological differentiation. High levels of telomerase activity were more frequently detected in poorly differentiated prostate cancer. None of the 10 samples taken from prostates with benign prostatic hyperplasia (BPH) or normal prostates expressed telomerase activity. In another 10 BPH samples obtained from prostate tissue adjacent to cancerous tissue, one of 10 samples (10%) showed weak telomerase activity. Furthermore, we investigated this activity in human prostate cancer cell lines (PC-3, LNCaP, and DU145) and all showed very high activity compared to normal human tissue samples. Four lymph nodes and one bone metastasis also exhibited extremely high telomerase activity. CONCLUSIONS: The present results indicate that telomerase activity might be a marker for detecting malignancy of the prostate and evaluating the malignant potential of prostate cancer.

[Comparative histological analysis of needle biopsy specimens, prostatectomized specimens and metastatic lymph nodes in prostatic adenocarcinoma--on the basis of the WHO histological classification].

The histological characteristics were comparatively analyzed among biopsy specimens, surgically removed prostates and metastatic lymph nodes obtained from 60 patients with prostatic adenocarcinoma treated by radical prostatectomy. According to the WHO-Mostifi's classification, the proportion of the 6 histologic components, large and/or small simple glands (LSG), micro-glands (MIC), cribriorm (CRB), fused glands (FUS), medullary/solid (MED) and columns-cords/trabecular (C-C), was determined semiquantitatively. LSG, MIC, and CRB are androgen-sensitive components, while FUS, MED and C-C are androgen-refractory components. The proportions of 5 histologic components excluding MIC were similar in the biopsy and prostate specimens. In 78.3% of the patients, the presence (or absence) of androgen-refactory components in the biopsy specimens coincided with that in the prostate specimens. However, the histologic except for the C-C component. Metastatic lymph nodes contained androgen-refactory components in all cases and tended to have more CRB and FUS and fewer LSG. The histology of the needle biopsy specimens may reflect that of the prostate glands, and may serve as a valuable parameter for determining therapeutic modalities. In addition, androgen-refactory components are frequently present in lymph node metastasis.

[Combination therapy with 5-fluorouracil (5-FU), cisplatin (CDDP) and interferon alpha-2B (IFN alpha-2B) for advanced renal cell carcinoma].

Eleven patients with metastatic renal cell carcinoma received combination therapy with 5-fluorouracil (5-FU), Cisplatin (CDDP) and Interferon alpha-2b (IFN alpha-2b). For 5 days, 500 mg of 5-FU was administered by continuous intravenous infusion daily; 20 mg/m2 CDDP was injected intravenously daily for 5 days, and 3 or 6 million units of IFN alpha-2b was administered intramuscularly twice a week for 3 weeks. This treatment cycle was repeated every 3 weeks. One of 11 patients achieved a partial response, and the response rate was 9%. High grade toxicities (WHO grade 3 or 4), nausea and vomiting (27%), leukocytopenia (9%), anemia (9%) and thrombocytopenia (18%) were seen. One of the reasons that this regimen dose not appear to be effective may be the low total dose of 5-FU for renal cell carcinoma.