Polyamines modulate the binding of GABAA-benzodiazepine receptor ligands in membranes from the rat forebrain.

The effects of spermine, spermidine and putrescine on the binding of the GABAA-benzodiazepine receptor complex were examined in the hippocampus and frontal cortex membranes of the rat. The results demonstrated modulatory effects of polyamines on the binding of diazepam and flunitrazepam but not on that of GABA, muscimol and Ro 15-1788. When membranes were prepared without detergent, the polyamines enhanced the binding of diazepam. However, while the binding capacity increased after homogenization in the presence of the non-ionic detergent Triton X-100, the polyamines did not enhance the binding but inhibited the binding of diazepam and flunitrazepam at greater concentrations. Considered together with other studies, the present findings indicate that polyamines can modulate the binding characteristics of several different neurotransmitter receptor-ionophore complexes.     

Assessment of 5α-reductase activity in hirsute women: comparison of serum androstanediol glucuronide with urinary androsterone and aetiocholanolone excretion

OBJECTIVE Recent evidence suggests that androstanediol glucuronide (AG), a metabolite of dihydrotestosterone (DHT) formed in skin, is frequently elevated in hirsute women, presumably reflecting enhanced 5a-reductase activity. An alternative method of demonstrating 5a-reductase activity is the androsterone (A)/aetiocholano-lone (E) ratio in urine. A and E are the 5α- and 5β- reduced metabolites, respectively, of androstenedione, which is the principal metabolite of dehydroepiandrosterone (D). Although serum AG and the urinary A/E ratio have both been considered valid methods for assessing 5α-reductase activity, the two have not been previously compared in hirsute women. The present study was undertaken to assess 5a-reductase activity in hirsute patients as determined by these two different methods. PATIENTS AND MEASUREMENTS We surveyed 47 untreated women (ages 17–33) with various degrees of hirsutism. Serum testosterone, bioavailable testosterone, dehydroepiandrosterone sulphate, and AG were determined. Additionally, A, E and D were measured in 24-hour collections of urine. RESULTS For the 47 women, 37 had elevated blood levels of AG (17.4 ± 2.2, mean±SEM; normal <8 nmol/l), but only 18 of these had an increased urinary A/E ratio (> 1.5). All but one of the remainder had elevated urinary and/or serum androgen levels. Overall, no significant correlation between AG and A/E was observed. There was a highly significant correlation between AG in serum and A in urine (r= 0.82, P<0 001). AG was also positively related to dehydroepiandrosterone sulphate (r= 0.64; P< 0.005), bioavailable testosterone (r= 0.6; P<0001), aetiocholanolone (r= 0.58; P<0 001) and total testosterone (r= 0.52; P& 0.01). In contrast, A/E was not significantly related to androgen production. CONCLUSIONS There is a poor correlation between AG and the A/E ratio in hirsute women. Although AG may be raised by increased 5α-reductase activity, it is probably also affected by the presence of elevated androgens regardless of 5α-reductase activity.     

Spontaneous ovarian hyperstimulation mimicking an ovarian tumour

Ovarian hyperstimulation syndrome in a spontaneous singletonpregnancy is exceedingly rare. We report a case of ovarian hyperstimulationpresenting as bilateral ovarian masses in association with spontaneouspregnancy, occurring in a woman with disturbed liver function.A possible mechanism is discussed.     

Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease

Background

Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered.

How do monkeys view faces?—a study of eye movements

Face perception plays a crucial role in primate social communication. We have investigated the pattern of eye movements produced by rhesus monkeys (Macaca mulatta) as they viewed images of faces. Eye positions were recorded accurately using implanted eye coils, while neutral upright, inverted and scrambled images of monkey and human faces were presented on a computer screen. The monkeys exhibited a similar eye scan pattern while viewing familiar and unfamiliar monkey face images, or while viewing monkey and human face images. No differences were observed in the distribution of viewing times, number of fixations, time into the trial of first saccade to local facial features, and the temporal and spatial characteristics of viewing patterns across the facial images. However, there was a greater probability of re-fixation of the eye region of unfamiliar faces during the first few seconds of the trial suggesting that the eyes are important for the initial encoding of identity. Indeed, the highest fixation density was found in the eye region of all the face images. The viewing duration and the number of fixations per image decreased when inverted or scrambled faces were presented. The eye region in these modified images remained the primary area of fixation. However, the number of fixations directed to the eyes decreased monotonically from the upright images through the inverted versions to the scrambled face images. Nonetheless, the eyes remain the most salient facial substructure regardless of the arrangement of other features, although the extent of salience which they attain may depend both on the low level properties of the eyes and on the global arrangement of facial features. Electronic Publication     

Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.