Comparison of immediate-release and controlled release carbidopa/levodopa in Parkinson's disease. A multicenter 5-year study. The CR First Study Group.

Background: Motor response fluctuations and dyskinesias compromise long-term levodopa therapy in Parkinson's disease. Variations in plasma levodopa levels contribute to adverse reactions associated with chronic therapy. Therefore, sustained-release levodopa preparations may be associated with less motor fluctuations and a better outcome.

Expansion of lymphokine-activated killer cells for clinical use utilizing a novel culture device.

Two major problems encountered in the application of lymphokine-activated killer (LAK) cell therapy in man are the massive culture volumes required for LAK cell induction and the paucity of LAK cells available for administration (human doses are less than or equal to 10% of effective murine LAK cell doses). We have, therefore, developed and tested a plastic porous culture device, Sclair plastic bags (E.I.

A procedure for the statistical evaluation of Ames Salmonella assay results. Comparison of results among 4 laboratories.

Ames Salmonella test data collected in our laboratory and 3 National Cancer Institute contract laboratories were analyzed to study the distribution of experimental errors associated with the test. It is shown that the Poisson distribution is not appropriate, and that the power transformation model Y = (revertants/plate)lambda, with lambda = 0.2 as estimated by the methods of Box and Cox, produced a measurement scale on which the experimental errors could be adequately described by a normal (Gaussian) distribution with a constant variance.

The use of cytogenetic monitoring in the workplace: a position paper of the American Industrial Health Council.

Although tests to determine cytogenetic effects can be used to identify workers who have been exposed to certain agents, uncertainties remain. Tests to determine cytogenetic effects have not gained wide acceptance for routine monitoring in the workplace because of questions concerning their general applicability to detect exposure to a wide variety of agents and because of the lack of data showing a correlation between cytogenetic effects as detected in humans and adverse health effects. Unless those issues are resolved, the measurement of cytogenetic effects for workplace monitoring purposes should be regarded as experimental and such measurement is not likely to become a routine workplace exposure monitoring technique.

A statistical method for analysis of mouse lymphoma L5178Y cell TK locus forward mutation assay. Comparison of results among three laboratories.

Analysis of data from our laboratory and that of two National Cancer Institute contractor laboratories indicate the random variation in the results of the mouse lymphoma L5178Y cell TK locus mutation assay can be adequately described by a lognormal distribution. This indicates that transformation of mutant frequencies to logarithms enables one to properly use well-known statistical techniques such as analysis of variance, regression analysis, and Student's t-test for the interpretation of data from this assay. The consistency of the lognormal distribution among laboratories is demonstrated.

Design of a statistical method for the analysis of mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase locus of cultured Chinese hamster ovary cells.

Mutagenesis data collected in the mammalian cell CHO/HGPRT assay were analyzed to study the distribution of the experimental errors associated with the test. The data neither followed the widely assumed Poisson distribution nor satisfied the usual statistical assumptions of normality and homogeneous variance of experimental errors. We transformed the data by using the power formula Y = (X + A) gamma where X is the observed mutation frequency, Y is the transformed frequency, and A and gamma are constants determined by the procedure of Box and Cox.

Control of argininosuccinate synthetase by arginine in human lymphoblasts.

Human lymphoblasts in long-term culture have the enzyme activities necessary to convert citrulline to arginine: argininosuccinate synthetase and argininosuccinate lyase. Upon transfer from arginine-supplemented to citrulline-supplemented medium, lymphoblasts exhibit a lag period before resuming exponential growth. During this lag the specific activity of argininosuccinate synthetase increases an average of 60-fold.

Questioning of reported evidence for guanosine tetraphosphate synthesis in a ribosome system from mouse embryos.

In 1974, Irr, Kaulenas and Unsworth reported that ppGpp is synthesized by cytosolic ribosomes from mouse embryos and proposed a role for ppGpp in the process of differentiation. This proposal is being challenged because ribosomes of mouse embryos from various stages of development and of mouse embryoid bodies were completely inactive in ppGpp formation.

Maturation of ribosomal RNA in stringent and relaxed bacteria.

Experiments with relaxed and stringent strains of E. coli confirm that rRNA synthesis continues in both during amino acid starvation. rRNA species produced are exclusively in their precursor configurations and vulnerable to nuclease attack.

L-arabinose isomerase formation in a conditional mutant of gene araA of Escherichia coli B-r.

A temperature-sensitive mutant of Escherichia coli in which the synthesis of l-arabinose isomerase is blocked during growth at 42 C was found to possess the following properties. (i) The mutation occurred in the structural gene for the isomerase, gene araA. (ii) During growth at elevated temperatures the mutant accumulates a product which is a precursor to the active enzyme.

Control of nucleotide metabolism and ribosomal ribonucleic acid synthesis during nitrogen starvation of Escherichia coli.

Ribosomal ribonucleic acid (RNA) synthesis and ribonucleoside triphosphate metabolism were studied in cultures of Escherichia coli subjected to starvation for inorganic nitrogen. In a strain that was under stringent control, a 50-fold reduction in the formation of both 16S and 23S RNA was accompanied by a severe restriction on nucleotide biosynthesis. These inhibitions were relieved in part by incubating the starved cells with amino acids.

Control of expression of the L-arabinose operon in temperature-sensitive mutants of gene araC in Escherichia coli B-r.

Expression of the l-arabinose operon in Escherichia coli B/r is dependent on the temperature of growth of the araC mutants reported in this paper. Analysis of these temperature-sensitive regulatory mutants indicates that both repressor and activator activities are thermolabile. The simplest model to explain the manner in which the operon is controlled is one suggesting that the regulatory gene, araC, codes for a protein which upon synthesis acts as a repressor molecule and prevents operon function.

Positive control of enzyme synthesis by gene C in the L-arabinose system.

Englesberg, Ellis (University of Pittsburgh, Pittsburgh, Pa.), Joseph Irr, Joseph Power, and Nancy Lee. Positive control of enzyme synthesis by gene C in the l-arabinose system.