A cytokine mRNA-destabilizing element that is structurally and functionally distinct from A+U-rich elements

The control of mRNA stability is crucial to the regulation of cytokine expression. We describe here a novel, potent destabilizing element found in the 3' untranslated region of granulocyte colony-stimulating factor mRNA. This element, which appears to require at least one stem-loop structure, we term the stem-loop destabilizing element (SLDE). Functionally equivalent elements appear to also exist in the interleukin 2 and interleukin 6 mRNAs. The SLDE is functionally distinct from the A+U-rich elements, which are also present in these and other cytokine mRNAs, because it destabilizes a chimeric mRNA in a tumor cell line in which A+U-rich elements do not function. In addition, the effect of the SLDE is insensitive to calcium ionophore and is therefore regulated independently of A+U destabilizing elements. The existence of two distinct mRNA-destabilizing elements provides an additional mechanism for the differential regulation of cytokine expression.     

Assessment of uterine arterial notching as a screening test for adverse pregnancy outcome

Recombinant papillomavirus-like particles have recently been shown to be highly effective for the prevention of papillomavirus infections and associated tumors, and a virus-like particle-based vaccine against the most prevalent HPV causing genital infection in humans will be developed in the near future. Another use of these virus-like particles may lie in gene therapy and DNA immunization. We report here that human papillomavirus-like particles composed of the major capsid protein (L1) of HPV-16 are able to package unrelated plasmid DNA in vitro and then to deliver this foreign DNA to eukaryotic cells with the subsequent expression of the encoded gene. The results indicate higher gene transfer than with DNA alone or with liposome. Virus-like particles are a very promising vehicle for delivering genetic material into target cells. Moreover, the preparation of the gene transfer vehicle is relatively easy.     

Short tube decompressive jejunostomy

Experience with short tube decompressive jejunostomy in twenty-nine patients with small bowel obstruction is presented. Many advantages are gained by operative decompression of obstructed, dilated small bowel. The favorable results with its use make short tube decompressive jejunostomy a safe, acceptable method of decompressing dilated small bowel.     

The influence of CSF calcium and magnesium on the ventilatory response to carbon dioxide during hyperoxia

Respiratory responses to inhaled carbon dioxide were measured in anaesthetized cats during perfusion of the ventriculocisternal system with artificial cerebrospinal fluid. A study was performed to evaluate the effect of changes in the magnesium and/or calcium concentration of the CSF on the CO2 response curve which was described as VE = S (PCSF, CO2 -- B). A decrease of S was observed when the magnesium concentration of the perfusion fluid was increased; the B-value remaining the same. The reverse was true down to magnesium concentrations of 0.6 mmol-1-1. Below this concentration S remained the same or decreased; the B-value was lowered. When both the calcium and magnesium concentrations of the CSF were changed, the relation between S and these concentrations could be described as to be proportional to CCAa-CMgb. The effect of changes in the calcium concentration was much more pronounced than comparable changes of the magnesium concentration as reflected by the magnitude of the exponents a and b which were found to be -2.80 (S.D. 0.11) and -0.60 (S.D. 0.03) respectively.     

Heptadecapeptide gastrin: measurement in blood by specific radioimmunoassay

The characteristics are described of an antibody (designated L6) which has virtually absolute specificity for heptadecapeptide gastrin. This antibody binds G17, but does not bind peptide fragments or molecular forms of gastrin comprising G17 with either amino acid deletions, or additions, at the carboxyl- and amino-terminals. In serum from patients with Zollinger-Ellison syndrome the only form of gastrin revealed by L6 was compatible with G17, and there was good agreement between estimated G17 concentrations in serum analyzed by gel filtration and by direct radioimmunoassay using L6. Using L6 in conjunction with antibodies specific for carboxyl- and amino-terminals of G17 it has been possible to measure concentrations of different forms of gastrin in serum of normal subjects after a meal in greater detail than previously possible. After a light meal consisting of eggs, toast, and Oxo, serum concentrations of G17 measured by L6 increased to a peak 20 min after feeding (delta gastrin, 19 pmoles per liter; n = 17). In contrast, concentration of G34 peaked at 50 min (delta gastrin, 27 pmoles per liter). Small amounts of amino-terminal fragments of G17 were present throughout the digestive period. Applying the known ratio of biological potencies of G34 and G17 for stimulation of acid secretion in man, it is estimated that G17 accounts for about 75% of the biological activity in blood after a meal, even though G34 is present in higher molar concentrations.     

Sphingolipid base metabolism. Sphinganine-1-phosphate lyase: identification of ethanolamine 1-phosphate as product

Ethanolamine 1-phosphate has been characterized as a product of the action of rat liver microsomal sphinganine 1-phosphate lyase on erythro-sphinganine 1-phosphate. The product was characterized by various forms of chromatography, gas-liquid chromatography-mass spectral analysis of appropriate derivatives, and by conversion to ethanolamine. The results of detailed studies of the mass spectral fragmentation of the tetra-trimethylsilyl derivative of ethanolamine 1-phosphate are also reported.