Confidence Intervals on the Total Variance in an Unbalanced Two-fold Nested Design

Confidence intervals on the total variance in an unbalanced random two-fold nested design are constructed and compared. Computer simulation indicates the proposed intervals provide confidence coefficients that are generally close to the stated level.     

Metabolism of Glutamic Acid in Aspergillus ochraceus During the Biosynthesis of Ochratoxin A

The uptake and utilization of glutamic acid in the biosynthesis of ochratoxin A by Aspergillus ochraceus were studied. Uniformly labeled L[14C]glutamic acid was incorporated into both the phenylalanine and isocoumarin moieties of ochratoxin A. Penicillic acid was also labeled. During the early stages of development, the amino acid was used mainly for the synthesis of ribonucleic acid and protein. A portion of glutamic acid was oxidized and was recovered as metabolic 14CO-2. The initial uptake velocity of glutamic acid decreased with age and was pH and temperature dependent. No relationship was found between the initial uptake velocities and ochratoxin A biosynthesis.     

Histone acetylation during early stages of sea urchin (arbacia punctulata) development

A correlation has been found between histone acetylation and gene activation at the time of gastrulation in the sea urchin, Arbacia punctulata. Between the blastula and gastrula stages, there is a 2.5-fold increase in the rate of acetylation of a histone fraction consisting of slightly lysine-rich and argininerich components, with a marked decrease in the fully differentiated pluteus stage. This pre-gastrular increase in histone acetylation is not correlated with (1) a decrease in the rate of histone deacetylation; (2) a decrease in acetyl coenzyme A pool size; (3) an increase in acetate uptake; (4) histone synthesis. The results thus suggest that increased histone acetylation may be at least one preparative factor for the activation of new genes at gastrulation.     

Improved survival in tumor-bearing SCID mice treated with interferon-γ-inducible protein 10 (IP-10/CXCL10)

Tumor growth requires angiogenesis, which in turn requires an imbalance in the presence of angiogenic and angiostatic factors. We have shown that the CXC chemokine family, consisting of members that are either angiogenic or angiostatic, is a major determinant of tumor-derived angiogenesis in non-small-cell lung cancer (NSCLC). Intratumor injection of interferon-inducible protein 10 (IP-10, or CXCL10), an angiostatic CXC chemokine, led to reduced tumor growth in a SCID mouse model of NSCLC. In this study, we hypothesized that treatment with CXCL10 would, by restoring the angiostatic balance, improve long-term survival in NSCLC-bearing SCID mice. To test this hypothesis, A549 NSCLC cells were injected in the subcutis of the flank, followed by intratumor injections with CXCL10 continuously (group I), or for ten weeks (group II), or a control group (human serum albumin). Median survival was 169, 130, and 86 days respectively (P<0.0001). We extended these studies to examine the mechanism of prolonged survival in CXCL10-treated mice. CXCL10 treatment inhibited lung metastases, but was dependent upon continued treatment, and was associated with an increased rate of apoptosis in the primary tumor, with no direct effect on the proliferation of the NSCLC cells. Furthermore, the inhibition of lung metastases was due to the angiostatic effect of CXCL10 on the primary tumor, since the rate of apoptosis within lung metastases was unaffected. These data suggest that anti-angiogenic therapy of human lung cancer should be continued indefinitely to realize persistent benefit, and confirms the anti-metastatic capacity of localized angiostatic therapy.