The cloning and characterization of a second brain enzyme with NAAG peptidase activity.

The peptide neurotransmitter N-acetylaspartylglutamate is inactivated by extracellular peptidase activity following synaptic release. It is speculated that the enzyme, glutamate carboxypeptidase II (GCPII, EC 3.14.

Synthesis of urea-based inhibitors as active site probes of glutamate carboxypeptidase II: efficacy as analgesic agents.

The neuropeptidase glutamate carboxypeptidase II (GCPII) hydrolyzes N-acetyl-L-aspartyl-L-glutamate (NAAG) to liberate N-acetylaspartate and glutamate. GCPII was originally cloned as PSMA, an M(r) 100,000 type II transmembrane glycoprotein highly expressed in prostate tissues. PSMA/GCPII is located on the short arm of chromosome 11 and functions as both a folate hydrolase and a neuropeptidase.

NAAG fails to antagonize synaptic and extrasynaptic NMDA receptors in cerebellar granule neurons.

The peptide transmitter N-acetylaspartylglutamate (NAAG) selectively activates the group II metabotropic glutamate receptors. Several reports also suggest that this peptide acts as a partial agonist at N-methyl-D-aspartate (NMDA) receptors but its putative antagonist effects have not been directly tested. To do this, we used whole cell recordings from cerebellar granule cells (CGC) in culture that allow the highest possible resolution of NMDA channel activation.

Colposcopy information leaflets: what women want to know and when they want to receive this information.

Objectives: To evaluate whether the information leaflets produced by UK colposcopy clinics provide women with the information they desire and to determine when they would like to receive this information.

Design: Questionnaire study and structured evaluation.

Setting: The colposcopy clinic of a UK cancer centre.

An observational study of precolposcopy education sessions: what do women want to know?

Nursing staff at a specialist hospital unit held five precolposcopy counselling and educational sessions; 47 women attended. We undertook a content analysis of the issues raised by the women. Our analysis confirms that there are significant fears concerning the procedure itself and underlying fears about cervical cancer.

Comparisons of self-report data and oral fluid testing in detecting drug use amongst new treatment clients.

Drug testing is widely used and employed in diverse contexts, including drug treatment clinics. Building on previous research, this paper aims to (i) compare self-report data and oral fluid (OMT) testing in detecting drug use amongst individuals beginning a new episode of drug treatment and (ii) identify factors that may predict drug users who have discordant self-report and OMT test results. Two hundred and seventy-one new drug treatment clients completed a structured questionnaire that included questions relating to drug use during the preceding 3 days and provided an oral fluid sample that was independently tested for opiates, benzodiazepines, methadone and cannabis.

GABA-induced neurite outgrowth of cerebellar granule cells is mediated by GABA(A) receptor activation, calcium influx and CaMKII and erk1/2 pathways.

During neuronal development, GABAA-mediated responses are depolarizing and induce an increase in the intracellular calcium concentration. Since calcium oscillations can modulate neurite outgrowth, we explored the capability of GABA to induce changes in cerebellar granule cell morphology. We find that treatment with GABA (1-1000 microm) induces an increase in the intracellular calcium concentration through the activation of GABA(A) receptors and voltage-gated calcium channels of the L-subtype.

GABA(A) receptor beta3 subunit deletion decreases alpha2/3 subunits and IPSC duration.

Deletion of the beta3 subunit of the GABA(A) receptor produces severe behavioral deficits and epilepsy. GABA(A) receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) in cortical neurons in cultures from beta3 -/- mice were significantly faster than those in beta3 +/+ mice and were more prolonged by zolpidem. Surface staining revealed that the number of beta2/3, alpha2, and alpha3 (but not of alpha1) subunit-expressing neurons and the intensity of subunit clusters were significantly reduced in beta3 -/- mice.

Can pre-colposcopy sessions reduce anxiety at the time of colposcopy? A prospective randomised study.

The main objective of this prospective randomised study was to evaluate whether offering pre-colposcopy group sessions reduces anxiety at the time of colposcopy. We also examined whether this strategy improved knowledge about abnormal smears and colposcopy and improved satisfaction with the colposcopy service provided. One hundred and forty-seven women undergoing colposcopy for the first time were randomised into two groups.

A comparison of the molecular specificities of whole cell and endonuclear phosphatidylcholine synthesis.

Deuterated choline-d(9) labelling of IMR-32 cells enabled comparison of the molecular specificities of whole cell and endonuclear phosphatidylcholine synthesis after 96 h polyunsaturated fatty acid supplementation. Surprisingly, while cell phosphatidylcholine synthesis and remodelling reflected a pattern of polyunsaturated fatty acid accretion, the saturated endonuclear phosphatidylcholine pool was only transiently labelled with polyunsaturates. Periodic endonuclear accumulations of the lipid second messenger diacylglycerol, mobilised from unsaturated phosphatidylinositol or saturated phosphatidylcholine, accompany cell proliferation.

Deletion of the glutamate carboxypeptidase II gene in mice reveals a second enzyme activity that hydrolyzes N-acetylaspartylglutamate.

Glutamate carboxypeptidase II (GCPII, EC 3.14.17.

Molecular modeling of the interactions of glutamate carboxypeptidase II with its potent NAAG-based inhibitors.

Glutamate carboxypeptidase II (GCPII, NAALADase, or NAAG peptidase) is a catalytic zinc metallopeptidase. Its extracellular domain hydrolyzes the abundant neuropeptide, N-acetyl-L-aspartyl-L-glutamate (NAAG), to produce N-acetylaspartate and glutamate following the synaptic release of this transmitter. Thus, GCPII influences the extracellular concentrations of both glutamate and NAAG.

Good practice towards homeless drug users: research evidence from Scotland.

Evidence of large numbers of people who are both homeless and drug dependent, the complexity of their needs, and the many difficulties which they can encounter when trying to access assistance highlight the importance of basic standards of good practice in working with homeless drug users. This is particularly relevant given the growth of new managerialism and the expansion of social care markets occurring within the UK public sector since the 1980s. Within this context, the aim of the present paper is to further understanding of how best to provide support to homeless drug users by examining good practice from the perspectives of both service providers and service users.

Offering routine antenatal testing for HIV and hepatitis B in the rural setting of Cornwall.

Before Department of Health directives to offer HIV and hepatitis B (HBV) testing to all pregnant women, there was little such screening in Cornwall. Through a multiagency collaborative approach a new antenatal screening programme for HIV/HBV has been introduced with high uptake in the first year (HIV 92% and HBV 93%). We also report the findings of a questionnaire survey of community midwives who alone offer antenatal HIV/HBV testing in Cornwall.

Drug users' views of drug service providers.

In Britain, there are a wide range of agencies providing many types of service to drug users. Such provision, it is argued, should be monitored and evaluated in the same way as provision to other client groups. To this end, the paper focuses on one aspect of drug service evaluation; users' views of service providers.

Ribozyme-mediated reduction of the GABA(A) receptor alpha1 subunit.

As an approach to understanding the role of the alpha1 subunit of the GABA(A) receptor, ribozymes were designed to reduce expression of this subunit protein by hydrolysis of alpha1 subunit message and antisense inactivation. The ribozyme cleavage sites were selected through homology comparison of all known murine GABA(A) receptor subunits at the amino acid and nucleotide sequence level. Two ribozymes were designed and synthesized: one against the extracellular domain and the other against the cytoplasmic domain.

beta-NAAG rescues LTP from blockade by NAAG in rat dentate gyrus via the type 3 metabotropic glutamate receptor.

N-Acetylaspartylglutamate (NAAG) is an agonist at the type 3 metabotropic glutamate receptor (mGluR3), which is coupled to a Gi/o protein. When activated, the mGluR3 receptor inhibits adenylyl cyclase and reduces the cAMP-mediated second-messenger cascade. Long-term potentiation (LTP) in the medial perforant path (MPP) of the hippocampal dentate gyrus requires increases in cAMP.

Gliomatosis cerebri in a 10-year-old girl masquerading as diffuse encephalomyelitis and spinal cord tumour.

Gliomatosis cerebri is the unifying term used when diffuse glial infiltration occurs throughout the cerebral hemispheres. The very few cases reported in children have presented with intractable epilepsy, corticospinal tract deficits, unilateral tremor, headaches, and developmental delay. Antemortem diagnosis is difficult because of the vagueness of the physical, radiological and pathological findings.

Nurse practitioners and physicians: a collaborative practice.

The rapid evolution of health care delivery within the United States has created increased opportunities for nurse practitioners (NPs) to work in a variety of challenging advanced practice roles and to impact the quality of health care. The NP role was originally developed to meet a perceived shortage of primary care physicians, especially for underserved populations. Today, NPs work in various fields, such as geriatrics and women's and family health care, as well as in various systems such as private practice and health maintenance organizations.

NAAG inhibits KCl-induced [(3)H]-GABA release via mGluR3, cAMP, PKA and L-type calcium conductance.

The peptide neurotransmitter, N-acetylaspartylglutamate (NAAG), is a selective agonist at the type 3 metabotropic glutamate receptor (mGluR3) where it acts to decrease cAMP levels. Rat cortical interneurons express both NAAG and glutamic acid decarboxylase, as well as mGluR3 mRNA. In the presence of ionotropic glutamate receptor antagonists, both NAAG and the group II metabotropic glutamate receptor agonist, DCG-IV, reduced the calcium-dependent, KCl-induced [(3)H]-GABA release from rat cortical neurons by 35%.

Impact of gender and having children in the household on ambulatory blood pressure in work and nonwork settings: a partial replication and new findings.

Ambulatory blood pressure (ABP) has been shown to differ for men and women across work and nonwork settings. For men, ABP is higher at work than at home on workdays or on nonworkdays. For women, ABP levels in different settings depend on whether they have children in the household.