Functional imaging of a large demyelinating lesion.

PURPOSE: To determine the metabolic characterization of a large solitary demyelinating lesion. METHODS: Magnetic Resonance Spectroscopy (MRS) and Positron Emission Tomography (PET) studies with 2-deoxy-2-[F-18]fluoro-d-glucose (FDG), carbon-11-methionine (methionine) and carbon-11-choline (choline) were done on the demyelinating lesion. RESULTS: The demyelinating lesion exhibited a low glucose uptake, prominent methionine uptake and a minimal choline uptake on the PET studies. MRS data revealed an increased choline to creatine (cho/cr) ratio and a decreased N-acetyl-aspartate to creatine (NAA/cr) ratio, which demonstrated a return to near normal ratios on follow-up study. CONCLUSION: The report summarizes the metabolic characteristics of a demyelinating plaque.

Site-specific recombination functions of bacteriophage lambda: DNA sequence of regulatory regions and overlapping structural genes for Int and Xis.

Site-specific recombination in bacteriophage lambda is mediated by two phage-encoded proteins, Int and Xis. The structural genes encoding these proteins are located immediately to the right of their site of action, the phage att site. The DNA sequence for both the structural and regulatory regions of these genes has been determined. The location and reading frame of the xis gene were ascertained by sequence comparisons with the b538 deletion (that ends within xis) and with the xis6 amber mutation. From the DNA sequence Xis has a molecular weight of 8630; it is rich in basic amino acids with lysine and arginine comprising 25% of the 72 amino acids. Identification of the int reading frame was also unambiguous. From the DNA sequence, Int has a molecular weight of 40,330; of the 356 amino acids, 69 are basic and 46 are acidic. In the NH(2)-terminal portion of Int, 35% of the first 20 amino acids are basic. The site-specific recombination functions form a very tight cluster (att-int-xis) on the lambda chromosome. The combined protein-encoding sequences of xis and int start 1347 base pairs, and terminate 84 base pairs, from the center of the phage att site. The two genes overlap one another by 20 base pairs (xis is upstream of int) and a possible means of controlling the relative synthesis rates of Int and Xis at the level of translation is proposed. Control at the level of transcription is also considered. The mutation intc226 leads to constitutive production of Int, independent of cII/cIII activator proteins normally required for transcription from the p(I) promoter. It is shown that this mutation is the result of a single base change (in the fMet codon of the xis gene) that generates an improved promoter heptamer sequence. This result, in conjunction with comparisons with other promoter sequences and other sequences responding to cII/cIII action, leads to a tentative identification of the p(I) promoter and site of cII/cIII action.

An evaluation of the micronuclei test using triethylenemelamine, trimethylphosphate, hycanthone and niridazole.

To determine the feasibility of the micronuclei procedure for cytogenetic studies, a comparatively weak chromosome breaking agent, trimethylphosphate (TMP) and the potent alkylating agent, triethylenemelamine (TEM) were evaluated. The procedure followed was that of Matter and Schmid with the following modifications: (a) direct flushing of bone marrow with 0.2 ml calf fetal serum. (b) air drying slides for a period of only I h, and (c) the use of pH 6.0 phosphate buffer to dilute both Wright and Giemsa stains. With this technique a dose response curve was generated for both TMP and TEM, using mice as the experimental animal. With TMP, a doubling over background was found when a concentration of 0.5 g/kg per day for five days was administered. To establish a statistically significant doubling dose over the control, a minimum of five animals must be used with 2000 polychromatic cells being analyzed per animal. Of the two antischistosomal agents tested, hycanthone yielded an increase of 20-fold in the number of micronuclei over control at 40 mg/kg administered i.p. for five days, while with niridazole no increase in micronuclei at several concentrations tested both by single and multiple injection was found. The results obtained with these compounds compare favorably with what has been reported for the standard in vivo metaphase analysis.