Potentiation of antitumor activity of 1-phthalidyl 5-fluorouracil by acetazolamide

Summary The effect of acetazolamide (A.A.) on the antineoplastic activity of 1-phthalidyl 5-fluorouracil (PH-FU) against rat and mouse solid tumors was examined. A.A., an inhibitor of liver PH-FU hydrolase, had no antitumor activity but greatly enhanced the activity of PH-FU when coadministered. The potentiation was evaluated in terms of suppression of tumor growth and prolongation of the life-span of tumor-bearing animals. Studies also revealed that A.A. elevated the concentration of PH-FU in tumor tissues, where 5-fluorouracil is slowly liberated from PH-FU. The results are consistent with the hypothesis that A.A. prevents enzymic degradation of PH-FU in the liver and promotes its distribution into target organs.Abbreviations A.A. acetazolamide - CMC carboxymethyl cellulose - 5-FU 5-fluorouracil - HPLC high-performance liquid chromatography - PH-FU 1-phthalidyl 5-fluorouracil     

Effect of filler loading on resin cement bonding to silanized buildup composites

PURPOSE: To determine the effects of silanation for core buildup composites on bond strength of resin cement. METHODS: Three core buildup composites including FluoroCore LV, Core Restore, and Clearfil Photo Core, of which filler loadings were 65 wt%, 74 wt%, and 83 wt% respectively, were used. All composite specimens were randomly divided into four surface treatment groups of eight each as following; 1) 600-grit ground only, 2) 600-grit ground plus silanation, 3) 600-grit ground plus air-particle abrasion, 4) air-particle abrasion plus silanation. Following these treatments, 4-META/MMA-TBB resin (C&B Metabond) was bonded to the specimen surfaces. Completed specimens were stored in 37 degree C water for 24 hours, and then thermocycled 20,000 times (4 degree C - 60 degree C) before shear bond strengths were tested. Data were analyzed by two-way ANOVA and Scheffé's test for statistical significance (P < 0.05). RESULTS: Clearfil Photo Core, of which filler loading was the highest among the resin composites tested, treated with air-particle abrasion plus silanation obtained the highest bond strength. However, silanation alone was not effective for improving the bond strength.     

Radiographic and genetic diagnosis of sporadic hypochondroplasia early in the neonatal period

Hypochondroplasia is an autosomal dominant skeletal dysplasia expressing postnatal onset of short stature with mild rhizomelic shortening of the limbs. This manifestation leads to restricted prenatal diagnosis of the disorder. We report here on a sporadic case of a hypochondroplastic baby, whose prenatal sonographic measurements were serially recorded from 19 weeks of gestation. Mild shortening of the limbs became manifest after 26 weeks of gestation. Biparietal diameter was within the normal range throughout gestation. Both parents were of average stature. A tentative diagnosis of a nonlethal short-limb skeletal dysplasia was made. At birth, the clinical manifestations of the neonate were not characteristic, but the radiographic features raised the possibility of hypochondroplasia. Molecular analyses revealed a C to G mutation at nucleotide 1659 of the fibroblast growth factor receptor 3 (FGFR3) gene, a common mutation in hypochondroplasia.     

Interleukin-4 gene polymorphism is not involved in the risk of recurrent pregnancy loss

PROBLEM: Enhanced secretion of type-2 T-helper (Th2) cytokine is a characteristic feature in normal physiological pregnancy. A study has demonstrated defective production of interleukine-4 (IL-4) and other Th2 cytokine in women with recurrent pregnancy loss (RPL). Several studies have suggested that IL-4 variable number of tandem repeat (VNTR) gene polymorphism is probably associated with different IL-4 production. METHODS OF STUDY: The IL-4 VNTR genotypes were assessed in 109 Japanese women with RPL and 210 ethnically matched women experiencing at least one live birth and no spontaneous abortion. RESULTS: No significant differences in IL-4 VNTR genotype frequencies were found between the RPL and the control [B1B1 genotype (reference); B1/B2 and B2/B2 genotypes, odds ratio, 0.91; 95% confidence interval, 0.58-1.45]. CONCLUSION: The present study suggests that the IL-4 VNTR allele is not a major genetic regulator in RPL.     

A novel mechanism for regulating clonal propagation of mouse ES cells

Self-renewal and differentiation of embryonic stem (ES) cells are controlled by the combinatorial action of extracellular signals and regulation of gene expression. For characterizing the entire molecular mechanism governing these events, we first established a feeder- and serum-free culture system in which mouse ES cells could propagate in clonal density in keeping with proper pluripotency. Supplementation of peptide hormones such as adrenocorticotropic hormone (ACTH) is required to remove serum, and the key event in this phenomenon may be the inhibition of the adenylyl cyclase (AC) activity, as it replaces the effect of these peptides. Because ES cells themselves produce the same activity, the finding suggests a novel mechanism in which activation of AC restricts clonal propagation of pluripotent stem cells.     

FISH analysis of BRCA1 copy number in paraffin-embedded ovarian cancer tissue samples

We investigated the BRCA1 gene copy number in unselected ovarian malignancies. Both additional genes (amplification) as well as deletion (loss of heterozygosity, LOH) are often thought to have a role in the initiation or progression of cancer. In addition, if there were little change, deletion studies might help identify BRCA1 mutation carriers. Forty-seven paraffin-embedded ovarian tissue blocks obtained between 1984 and 1997 were used for this study. A sample was "deletion-positive" when BRCA1-deleted cells in the tumor area were significantly different from the benign area. Twenty-five (53%) cases were found to be "deletion-positive". The average age of onset of "deletion-positive" patients was 50.8 years and of "deletion-negative" 57.8 years (P < 0.05). There was no statistical difference between groups in the staging, histology, or prognosis. A Kaplan-Meier study did show a trend towards poorer survival for "deletion-positive" patients. FISH permits unique molecular characterization of malignancies at a cellular level. Double amplification of HER-2 and c-myc predicts poor ovarian cancer survival. There appears to be a definite role for BRCA1 deletion in reducing the age of ovarian cancer onset and possibly in overall survival. Further FISH studies of this and other patient sets using additional molecular markers are needed.     

Mechanism of action of voltage-gated K+ channel antibodies in acquired neuromyotonia

Acquired neuromyotonia (ANM) is associated with antibodies to voltage-gated K+ channels (VGKCs). ANM sera reduce the number of K+ currents in neuronal cell lines, but it is not clear how the antibodies act. Here, we show by using the NB-1 cell line that the reduction in K+ currents by IgG is independent of added complement. IgG Fc and Fab fragments from ANM sera had no effect, but three of four ANM F(ab')2 fragments significantly reduced K+ currents. Thus, cross-linking of the channels by divalent antibodies is likely to be an important mechanism in reducing K+ currents.     

Neonatal sudden death due to Legionella pneumonia associated with water birth in a domestic spa bath

We report the first case of neonatal Legionnaires' disease associated with water birth in a spa bath at home. Legionella pneumophila serogroup 6 was detected from postmortem lung tissue.