Trace amines and Tourette's syndrome

There has been considerable interest in recent years in possible neurochemical abnormalities in Tourette's Syndrome (TS). In studies combining neuropsychological and neurochemical measurements, we have investigated the possible roles of trace amines in this disorder. Urinary levels of free -phenylethylamine (PEA) and plasma levels of its precursor amino acid phenylalanine were decreased in TS patients when compared to values in normal children. These urinary PEA levels in TS patients were inversely related to several scores from the Tourette's Syndrome Global Scale (TSGS). Further investigation of the group of subjects with low urinary PEA indicated that they also had low levels of MHPG, normetanephrine, 5-HT andm- andp-tyramine. Patients with low PEA were also compared on an extensive battery of neuropsychological measures and observed to perform significantly worse than TS patients with normal urinary PEA levels. Biochemical measurements also suggest a possible abnormality in tryptamine turnover in TS since urinary levels of indole-3-acetic acid (IAA; the acid metabolite of tryptamine) are significantly lower in TS patients than in normal controls.     

Fatty Acyl-CoA Inhibits 1-Alkyl-sn-Glycero-3-Phosphate Acetyltransferase in Microsomes of Immature Rabbit Cerebral Cortex: Control of the First Committed Step in the De Novo Pathway of Platelet-Activating Factor Synthesis

Abstract: Microsomal fractions of cerebral cortices of 15-day-old rabbits were used to study the 1-alkyl- sn -glycero-3-phosphate (AGP) acetyltransferase that generates 1-alkyl-2-acetyl- sn -glycero-3-phosphate in the de novo path of platelet-activating factor synthesis. The AGP acetyltransferase activity was inhibited by small concentrations of medium-long chain fatty acyl-CoA thioesters. In contrast, the AGP acyltransferase used oleoyl-CoA as substrate and was not inhibited by the presence of acetyl-CoA in high molar excess. The inhibition of AGP acetyltransferase was seen at concentrations of oleoyl-CoA as low as 0.5 µ M using 12.5 µ M AGP and 200 µ M acetyl-CoA. The inhibition by oleoyl-CoA was noncompetitive for the acetyl-CoA substrate. However, there was evidence that the oleoyl-CoA was competing with AGP in the acetyltransferase reaction, as the inhibition was lessened by increasing the AGP substrate concentration. Several acyl-CoA thioesters were effective as inhibitors of the AGP acetyltransferase, including oleoyl-, palmitoyl-, lauroyl-, and octanoyl-CoA. Propionyl- and butyryl-CoA were less effective as inhibitors, and propionyl-CoA was found to be a competitive inhibitor for acetyl-CoA. We have noted earlier that MgATP is an effective inhibitor of the AGP acetyltransferase and here we show that the inhibition by oleoyl-CoA can be increased by the presence of 0.1 m M MgATP. In brain ischemia, a decline in ATP levels would likely lead to a corresponding fall in acyl-CoA concentrations, thereby relieving the inhibition of AGP acetyltransferase and permitting the flow of AGP into the de novo pathway of platelet-activating factor synthesis.     

The population dynamics of the millipede, Ommatoiulus moreletii(Diplopoda: Iulidae)

The population dynamics of Ommatoiulus moreletii were studied in an open grassland and a dry sclerophyllous woodland in South Australia. During summer, O. moreletii aggregated in cool, moist sites (e.g. beneath tussocks of Lomandra fibrata (Liliaceae)) or burrowed underground. In autumn, the animals surfaced and dispersed. In a particularly hot and dry summer, mortality was demonstrated in the grassland but not in the woodland which was relatively cooler and moister. The survival of females from an autumn breeding season to the subsequent spring was inversely correlated with their maturity in autumn. The advantage to O. moreletii of survival of females after a poor breeding season is discussed with reference to den Boer's (1968) concept of "spreading of risk".     

Changes in serum trace element levels following local irradiation of a solid tumor.

The changes in concentrations of a number of trace elements have been determined by neutron activation analysis in tumor, liver, and blood serum of host animals, following local irradiation of a solid tumor (3924A Morris hepatoma). These trace element changes are compared to the changes observed in a parallel study of the effects of the chemotherapeutic agent 5-fluorouracil on the same tumor. Since the changes in some of the trace elements parallel the changes in pathological and biochemical factors resulting from the insult of radiation on the tumor, these trace elements may be valuable markers in the clinical evaluation of therapeutic response and as monitors of the long term effects of cancer therapy.     

Protease-nexin: A cellular component that links thrombin and plasminogen activator and mediates their binding to cells

This report identifies a component of normal human fibroblasts that forms a covalent linkage with thrombin and urokinase (urinary plasminogen activator) and mediates most of the specific cellular binding of these proteases. This component, here named protease-nexin (PN), is both associated with the cell surface and released into the culture medium. In several ways PN resembles antithrombin III (AT3), a prominent inhibitor of thrombin in serum: PN links thrombin, probably via an ester bond; PN does not link thrombin blocked at its catalytic site serine; PN has a high-affinity heparin-binding site; and heparin greatly accelerates the rate of linkage between soluble PN and thrombin. Despite these similarities, PN and AT3 are distinct; they differ in size and are not immunologically cross-reactive. Whereas AT3 regulates the proteolytic activity of thrombin in serum, PN may regulate the activity of serine proteases at and near the cell surface.