Adenosine deaminase activity in relation to the appearance of early and late Epstein-Barr virus antigens induced in lymphoblastoid cells

Summary Induction of Epstein-Barr virus (EBV) capsid antigen synthesis in 59.6% of P3HR-1 cells was followed by a decrease to 70% in adenosine deaminase (ADA) activity. In Daudi cells synthesizing EBV early antigen, ADA activity did not decrease.     

A Hypernychthemeral Sleep-Wake Syndrome: A Treatment Attempt

The wake and sleep-onset times of a patient with a sleep-wake cycle longer than 24 hr were recorded by the patient for 4 years. During this time, the patient found himself unable to maintain a 24-hr sleep-wake schedule. When treated with 1-2 mg clonazepam, taken nightly, he was able to become entrained to a 24-hr day. Despite entrainment of his sleep-wake cycle, the patient reported depression, lack of motivation and fatigue and chose not to continue taking the drug.     

In vivo chromosomal instability in ataxia-telangiectasia homozygotes and heterozygotes

Summary The exfoliated cell micronucleus test was used to monitor in vivo chromosomal instability in a population comprised of five ataxia-telangiectasia (A-T) homozygotes and seven obligate heterozygotes (parents of A-T patients). This assay was previously validated as a procedure for quantifying non-invasively carcinogen-induced chromosomal aberrations occurring in vivo in epithelial tissues of both the oral cavity and the urinary bladder. The procedure involved taking airdried smears of three sites in the oral cavity of each examined individual. Desquamated urinary bladder cells were collected by centrifugation of freshly voided urine samples. Frequencies of exfoliated cells in these preparations were determined and compared with control values (individuals with no genetic chromosomal instability and no known carcinogene exposure) for these sites. Exforliated cell micronucleus (MEC) frequencies were elevated 5- to 14-fold in samples from the A-T homozygotes. This elevation in MEC frequency occurred for both the oral cavity and urinary bladder. Five out of the seven obligate A-T heterozygotes had an elevated MEC frequency in samples from the oral cavity. In addition, all examined urine samples from A-T heterozygotes contained an elevated percentage of micronucleated cells. These data suggest that this assay is suitable for in vivo monitoring of groups of individuals in which genetically produced chromosomal damage occurs. The possibility of A-T heterozygote detection with this simple procedure is of particular significance, since such individuals are believed to comprise up to 1% of the general population, and have been identified as being at elevated risk for cancer.     

Modulation of the serotonin S2-receptor in brain after chronic lithium

In vivo effects of chronic lithium administration on dopaminergic and serotonergic receptor binding were studied in the striatum and cerebral cortex of the rat. [³H]Domperidone was used as the ligand for the dopaminergic receptor, and [³H]ketanserin for the serotonergic system. Long-term ingestion of lithium (2–3 months) resulted in high levels of lithium in the cerebral cortex and significantly higher potassium levels; the sodium content remained at normal levels. The kinetic constants (K _d andB _max) of [³H]domperidone binding sites measured in the striatum did not show any deviation from control values, but the receptor concentration (B _max) of [³H]ketanserin binding sites was significantly reduced in the cerebral cortex of lithium-treated rats. The apparent dissociation constant (K _d) was not changed. The results indicate that the serotonergic component of the [³H]spiperone binding site, which we had previously found to be affected by chronic lithium treatment and which was shown by Peroutka and Snyder (1) to be the 5-HT₂ receptor, is selectively affected by lithium.Special Issue dedicated to Prof. Eduardo De Robertis.     

Effects of replacement of active site residue glutamine 231 on activity and allosteric properties of aspartate transcarbamoylase.

Since crystallographic studies on Escherichia coli aspartate transcarbamoylase (ATCase) indicate that Gln 231 is in the active site of the enzyme and participates in the binding of the substrate, aspartate, it seemed of interest to examine mutant enzymes in which Gln 231 was replaced by Asn or Ile. The two mutant forms containing amino acid substitutions were characterized by a combination of steady-state kinetics, hydrodynamic measurements, and equilibrium ligand binding techniques. Both mutant forms exhibited a dramatic reduction in the affinity of the protein for substrates and substrate analogues as well as a very large decrease in catalytic activity. Moreover, the amino acid substitutions introduced within the active site of the enzyme led to unusual allosteric properties in the mutant enzymes. Although the bisubstrate analogue N-(phosphonoacetyl)-L-aspartate promotes the characteristic global conformational change in the mutant forms that is observed with the wild-type enzyme, the combination of substrate and substrate analogue does not. Cooperativity with respect to substrate binding is largely reduced compared to wild-type ATCase. Also, the effector molecules ATP and CTP which bind to the regulatory chains have dramatic effects on the activity of the mutant enzymes containing replacements for Gln 231 in the catalytic chains. In stark contrast to the wild-type enzyme, in which effects of nucleotides are manifested primarily by changes in the K0.5 of the enzyme, ATP and CTP have large effects on the Vmax of the mutant enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)