Results of clinical trials with a CMitF (cyclophosphamide, mitoxantrone, and 5-fluorouracil) regimen versus a CAF (cyclophosphamide, adriamycin, and 5-fluorouracil) regimen in advanced/relapsed breast cancer

Randomized clinical trials were conducted in patients with advanced/relapsed breast cancer, using CMitF (mitoxantrone, cyclophosphamide, and 5-fluorouracil) regimen in comparison with CAF (cyclophosphamide, adriamycin, and 5-fluorouracil) regimen. The response rate was 50% (13/26) for the CMitF group and 50% (10/20) for the CAF group. Classified by disease site, CAF group showed a tendency for a higher response rate in soft tissue, but in bone and viscera the rates were similar for both regimen groups. The median weeks to response (range) was 5 (3-21) weeks for the CMitF group, and 8 (3-22) weeks for CAF group, a tendency for slightly earlier response thus being shown in the CMitF group. The median duration of response (range) was 10 (4-47) weeks for the CMitF group, and 9 (4-50) weeks for CAF group, whereas by the method of Kaplan-Meier, at 40 weeks after the start of therapy, the proportion showing response still continued to be 60% for the CMitF group, which was a higher rate than the 27% for CAF group. The survival rate at 48 weeks was for both groups with no difference shown. Leukopenia, gastrointestinal symptoms and alopecia were major side effects in both groups, but the incidence and severity grade of gastrointestinal symptoms (nausea and vomiting) and alopecia were significantly less in the CMitF group than in CAF group. In both groups, the WBC nadir was 2,100/microliter and the time to nadir was 14 days, with no difference shown in hematological toxicity between the two groups. No severe cardiac, hepatic, or renal toxicity was noted.     

Synchronization of Ca(2+) oscillations among primate LHRH neurons and nonneuronal cells in vitro

Periodic release of luteinizing hormone-releasing hormone (LHRH) from the hypothalamus is essential for normal reproductive function. Pulsatile LHRH release appears to result from the synchronous activity of LHRH neurons. However, how the activity of these neurons is synchronized to release LHRH peptide in a pulsatile manner is unclear. Because there is little evidence of physical coupling among LHRH neurons in the hypothalamus, we hypothesized that the activity of LHRH neurons might be coordinated by indirect intercellular communication via intermediary (nonneural) cells rather than direct interneural coupling. In this study, we used an in vitro preparation of LHRH neurons derived from the olfactory placode of monkey embryos to assess whether nonneuronal cells, play a role in coordinating LHRH neuronal activity. We found that cultured LHRH neurons and nonneuronal cells both exhibit spontaneous oscillations in the concentration of intracellular Ca(2+) ([Ca(2+)](i)) at similar frequencies. Moreover, [Ca(2+)](i) oscillations in both types of cell were periodically synchronized. Synchronized [Ca(2+)](i) oscillations spread as intercellular Ca(2+) waves across fields of cells that included LHRH neurons and nonneuronal cells, although waves spread at a higher velocity among LHRH neurons. These results suggest that LHRH neurons and nonneuronal cells are functionally integrated and that nonneuronal cells could be involved in synchronizing the activity of the LHRH neurosecretory network.     

Performance of glaucoma mass screening with only a visual field test using frequency-doubling technology perimetry

PURPOSE: To report the performance of glaucoma mass screening with only a visual field test utilizing frequency- doubling technology (FDT) perimetry in general populations.DESIGN: Hospital and population-based cross-sectional study.METHODS: This study took place in a multicenter setting. One hundred three consecutive glaucomatous patients and 14,814 persons were randomly selected. We had created a glaucoma screening protocol (GSP) using FDT perimetry (FDT-GSP). Frequency-doubling technology-glaucoma screening protocol was tested on consecutive glaucoma patients diagnosed with Humphrey visual field analyzer (30-2 SITA standard), and then FDT-GSP was applied to general populations. Frequency-doubling technology-glaucoma screening protocol positive subjects were ophthalmologically diagnosed. Detection ability of FDT-GSP was determined in consecutive patients, and the positive predictive value (PPV) of FDT-GSP to detect definitive glaucoma was estimated in general populations.RESULTS: Frequency-doubling technique-glaucoma screening protocol detected 83.3% and 100% of definitive glaucoma patients with an early (mean deviation [MD] > -6 dB) and more advanced stage (MD < or = -6 dB), respectively. In the population-based screening, there were 660 (4.5%) subjects who had positive FDT-GSP, including 512 in whom no visual field abnormalities (VFA) had been pointed out previously. Of them, 370 subjects underwent ophthalmologic diagnosis. Then, 266 (71.9%, 266/370) subjects had a glaucomatous disk and 167 had definitive glaucomatous VFA. Fifty-five (14.9%) and 39 (10.5%) subjects were diagnosed as having other diseases and as normal, respectively. The PPV of FDT-GSP ranged from 32.6% (167/512)-45.1% (167/370).CONCLUSIONS: Frequency-doubling technology-based screening with only a visual field test showed reasonable performance on mass screening for detection of definitive glaucoma in this study population, considering the glaucoma prevalence.     

Involvement of endothelial cell adhesion molecules in the development of anti-Thy-1 nephritis

To study an involvement of glomerular endothelial cells in the development of anti-Thy-1 nephritis, we examined the expression of endothelial cell adhesion molecules during the course of this model. Ribonuclease protection assay elucidated that expression of mRNA for intercellular adhesion molecule-1 (ICAM-1) was markedly enhanced in the glomeruli with a peak at 2 h (6.5-fold, p < 0.05) after the anti-Thy-1 antibody injection when mesangial cell lysis was recognized and IL-1beta mRNA expression was induced in the glomeruli. The glomerular ICAM-1 was predominantly localized in the endothelial cells and was intensely immunostained at day 1 in the glomerular endothelial cells. In contrast, platelet endothelial cell adhesion molecule-1 (PECAM-1) and vascular endothelial-cadherin mRNA expression increased gradually with a peak at day 6 (2.6-fold (p < 0.05) and 4.2-fold (p < 0.05), respectively) in the glomeruli with mesangial proliferative lesion. PECAM-1 was also immunolocalized in the glomerular endothelial cells and the immunoreactivity was greatly enhanced at day 6. Glomerular expression of vascular cell adhesion molecule-1 and endothelial leukocyte adhesion molecule-1 (E-selectin) was unchanged at a low level during the course of anti-Thy-1 nephritis. Blocking of ICAM-1 by administration of anti-ICAM-1 antibody showed significant decrease in the number of polymorphonuclear leukocytes accumulating in the glomeruli by 45.7% (9.4 +/- 0.2 vs. 5.1 +/- 0.1 per glomerular cross section, p < 0.01) at 2 h. These results suggest a significant involvement of glomerular endothelial cells in the development and repair of anti-Thy-1 nephritis via direct or indirect intercellular interactions between mesangial cells and glomerular endothelial cells.     

Evidence that heterodimers exist in the fibrinogen Matsumoto II (gamma308N-->K) proband and participate in fibrin fiber formation

INTRODUCTION: In this report, we established the gamma308K/N fibrinogen-secreting Chinese hamster ovary (CHO) cell line, which is an artificially heterozygous, Matsumoto II (M-II; gamma308K-->N) type of dysfibrinogen, to indirectly demonstrate the existence of heterodimeric molecules in propositus plasma and the participation of these molecules in fibrin fiber formation. MATERIALS AND METHODS: We co-transfected the gamma-chain of gamma308K- and gamma308N-coding vectors into CHO cells expressing Aalpha- and Bbeta-chains and selected the clones by utilizing the unique electrophoretic mobility of the variant gamma-chain of gamma308K. Although sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis under reducing conditions showed that the amount of the variant gamma-chain was slightly less than the amount of normal gamma-chain in recombinant gamma308K/N fibrinogen, we judged that our selected clone was still a useful model of the M-II individual. RESULTS AND CONCLUSION: Functional analyses demonstrated that thrombin-catalyzed fibrin polymerization decreased in the following order: gamma308N, gamma308K/N, an equimolar mixture of gamma308K with gamma308N. The difference in the polymerization curves between gamma308N and gamma308K/N is highly similar to the difference between plasma fibrinogen from a normal control and the M-II proband. In addition, experimental results using the equimolar mixture indicated that gamma308K is able to polymerize into fibrin fibers and does not inhibit the gamma308N polymerization. In conclusion, our results indirectly demonstrated that gamma308K/N fibrinogen is the mixture of normal homodimers, heterodimers, and variant homodimers, and all of these can participate in the fibrin fiber formation.     

Evaluation of a contrast examination technique for three-dimensional CT angiography (3DCTA) of the head and craniocervical region

In three-dimensional CT angiography (3DCTA) studies, we make it a rule to use a CT number monitoring system (SureStart, Toshiba Medical Systems Company) to ensure that contrast-enhanced images are acquired at the optimal timing. However, although SureStart can accurately determine enhancement start timing, it is still possible to inject more contrast medium than necessary because the scan start time is not known with certainty. To address this problem, we conducted investigations to determine the ideal contrast examination technique using SureStart and an injector synchronization system. Our results showed that a CT number of 300 HU in the middle cerebral artery (M1) could be obtained with the injection of contrast medium for a period of 45 s (450 mgI/kg) for the head or for 50 s (450 mgI/kg) for the craniocervical region. This makes it possible to perform contrast studies with greater reproducibility by taking individual variation into consideration. Moreover, it was found that comparable results could be obtained by terminating the injection of contrast medium 15 s before the completion of the study and immediately injecting a physiological saline solution flush, permitting the volume of contrast medium to be further reduced.