Evidence that nitric oxide causes calcium-independent release of [3H] dopamine from rat striatum in vitro.

Nitric oxide (NO), liberated from the photoactive donor Roussin's black salt (RBS), was investigated for its ability to release tritium from [3H]dopamine-loaded rat striatal slices. Our results show that illumination of RBS-pretreated striatal slices caused an increase in basal dopamine release, which was reduced by approximately 73% in the presence of oxyhaemoglobin (10 microM), indicating that it was mediated by liberation of NO. The release was insensitive to removal of extracellular calcium yet was not due to gross cellular damage of the tissue, as there was no detectable increase in lactate dehydrogenase release.

Cellular localisation and co-expression of somatostatin receptor messenger RNAs in the human brain.

Genes for five high affinity somatostatin receptors, named sst1-5, have been cloned recently. In this study we describe the tissue distribution and cellular localisation of mRNA encoding sst1, sst3 and sst4 receptors in the human cerebellum, frontal cortex (Brodmann's area 11) and hippocampus. RT-PCR and in situ hybridisation studies indicated a distinct, but partially overlapping pattern of expression of the receptor mRNAs.

New insights on P2X purinoceptors.

Significant advances in understanding of P2X purinoceptor pharmacology have been made in the last few years. The limitations of nucleotide agonists as drug tools have now been amply demonstrated. Fortunately, inhibitors of the degrading ecto-ATPase enzymes are becoming available and it has become apparent that the complete removal of all divalent cations can be used experimentally in some systems to prevent nucleotide breakdown.

Somatostatin-induced contraction of human isolated saphenous vein involves sst2 receptor-mediated activation of L-type calcium channels.

A range of somatostatin (SRIF) analogues have been used to characterize the SRIF receptor-mediating contraction of the human saphenous vein. SRIF produced concentration-dependent contractions with an EC50 value of approximately 20 nM. The peptidase inhibitors phosphoramidon and amastatin did not alter the potency of SRIF.

Epidermal growth factor ligand-independent, unregulated, cell-transforming potential of a naturally occurring human mutant EGFRvIII gene.

The type III deletion-mutant gene for the epidermal growth factor receptor (EGFRvIII) is frequently expressed in glioblastomas and in breast and non-small cell lung carcinomas. To understand its contribution to the malignant phenotype in humans, we transfected NR6 cells with the mammalian vector pH beta APr-1-neo containing cDNA for either EGFRvIII or wild-type EGFR. Western blot analyses showed that NR6 transfected with wild-type EGFR (NR6W) contained a normal-sized protein (170 kilodaltons); cells transfected with EGFRvIII (NR6M) contained a truncated protein (145 kilodaltons).

Nicotinic and muscarinic receptor-evoked depolarizations recorded from a novel cortical brain slice preparation.

We have developed a novel cortical brain slice preparation for extracellular field-potential recording using the grease-gap barrier technique. This preparation allows the study of cholinergic and glutamatergic depolarization responses of neocortical pyramidal neurones whose axons pass through the corpus callosum to contralateral cortical areas. Concentration-effect curves to carbachol, 1,1-dimethyl-4-phenyl piperazinium (DMPP) and muscarine yielded mean EC50 values of 29.

Management of transient ischaemic attacks and stroke.

The management of stroke and transient ischaemic attacks (TIAs) has changed greatly in the last two decades. The importance of good blood pressure control is the hallmark of stroke prevention. Large multicentre trials have proven beyond doubt the value of aspirin in TIAs, warfarin in patients with atrial fibrillation and embolic cerebrovascular symptoms, and carotid endarterectomy in patients with carotid TIAs.

Somatostatin receptors mediating inhibition of basal and stimulated electrogenic ion transport in rat isolated distal colonic mucosa.

The aim of this study was to examine the potencies of several recently identified selective somatostatin (SRIF)-receptor ligands as inhibitors of electrogenic ion transport in the rat distal colonic mucosa with the view to identifying the SRIF receptor type involved. Under basal conditions, cumulative administration of SRIF and SRIF28 decreased short circuit current (SCC), a measure of electrogenic ion transport, with EC50 values of 4 nM and 9 nM respectively. The peptidase inhibitors, phosphoramidon (1 microM) and amastatin (10 microM), has no effect on the potencies of either SRIF or SRIF28.

Localization of P2X purinoceptor transcripts in the rat nervous system.

We used transcript-specific oligonucleotides to examine the localization in the rat nervous system of the corresponding mRNAs for the two P2X purinoceptor genes cloned recently from the rat vas deferens and PC12 cells. PC12 P2X purinoceptor mRNA was labeled in the olfactory tubercle, striatum, hypothalamus, hippocampus, dentate gyrus, amygdala, cortex, and cerebellum, whereas the vas deferens P2X purinoceptor-specific probes labeled the cerebellum and, at lower levels of expression, the striatum, hippocampus, and cortex. Both types of P2X purinoceptor transcript were found on cell bodies in the nodose and superior cervical ganglia.

Immunoreactive p53 protein in high-grade prostatic intraepithelial neoplasia.

p53 protein accumulation in the nuclei of prostatic carcinoma cells, as detected by immunohistochemistry, has been associated with increased cell proliferation rate, increased histologic grade and stage, androgen independence and decreased patient survival. Little is known, however, of p53 in prostatic intraepithelial neoplasia (PIN), the putative precursor proliferation for moderately to poorly differentiated peripheral zone carcinoma of the prostate. In this investigation, we utilized a panel of antibodies reactive with p53 protein to assess p53 protein accumulation in prostatic epithelial hyperplasia, PIN and prostatic carcinoma.

Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma.

Hepatocyte growth factor (scatter factor) and its receptor, the c-met proto-oncogene product (c-MET), have been implicated in embryogenesis, tissue reorganization, and tumor progression. Little is known, however, of the expression and functional significance of these molecules in prostatic cells and tissue. In this investigation, we assessed the expression of hepatocyte growth factor (HGF) and c-MET in prostatic tissues and cell lines and also determined the effect of purified recombinant HGF on cell proliferation and scattering of prostatic carcinoma cell lines.

Interobserver reproducibility in the diagnosis of prostatic intraepithelial neoplasia.

To assess interobserver reproducibility in the categorization of prostatic intraepithelial neoplasia (PIN) seven pathologists reviewed 25 lesions. Rather than classic or consecutive examples of PIN, cases were selected to represent the full spectrum of diagnostic issues in this field. Lesions were classified into one of six categories: (a) benign prostate tissue, (b) PIN1, (c) PIN2, (d) PIN3, (e) PIN3 cannot rule out associated cancer, and (f) PIN3 plus cancer.

Laparoscopic pneumodissection: a unique means of tissue dissection.

Purpose: To study the acute and chronic tissue effects of using high pressure CO2 to dissect tissues during laparoscopic procedures.

Materials And Methods: A 5-mm. laparoscopic pneumodissector, capable of delivering brief bursts of high pressure CO2 (20 to 100 psi), was discharged on a variety of porcine tissues including the renal hilum.

Effect of inflammation and benign prostatic hyperplasia on elevated serum prostate specific antigen levels.

Purpose: We quantify the causes of elevated serum prostate specific antigen (PSA) concentrations in men whose prostate biopsies repeatedly showed no cancer.

Materials And Methods: The effects of prostate volume, inflammation, echogenicity on ultrasound and calculi were examined in a large PSA-based screening population of 148 men with serum PSA concentrations greater than 4.0 ng.

Morphometric analysis and clinical followup of isolated prostatic intraepithelial neoplasia in needle biopsy of the prostate.

Purpose: We evaluate the significance of grade and extent of isolated prostatic intraepithelial neoplasia in prostate needle biopsies as a predictor of cancer on repeat biopsy.

Materials And Methods: We reviewed our experience with 58 men 50 years or older who had isolated prostatic intraepithelial neoplasia on initial prostate needle biopsy during a prostate specific antigen (PSA) based screening trial for prostate cancer. All 58 men underwent repeat biopsy to follow the initial findings of prostatic intraepithelial neoplasia.

Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas.

Despite molecular biological advances in understanding human cancers, translation into therapy has been less forthcoming; targeting neoplastic cells still requires that tumor-specific markers, preferably those on the cell surface, be identified. The epidermal growth factor receptor (EGFR) exists in a deletion-mutant form, EGFRvIII, which has been identified by genetic and immunological means in a subset of gliomas and non-small cell lung carcinomas. Specific polyvalent antisera to the extracellular portion of the variant were readily induced, but immunization using a synthetic linear peptide representing the unique EGFRvIII primary sequence has been unsuccessful in mice or macaques.

Evidence that [3H]-alpha,beta-methylene ATP may label an endothelial-derived cell line 5'-nucleotidase with high affinity.

1. In membranes prepared from a permanent cell line of endothelial origin (WEC cells), [3H]-alpha, beta-methylene ATP ([3H]-alpha, beta-meATP) labelled high (pKd = 9.5; Bmax = 3.

Fusacandins A and B; novel antifungal antibiotics of the papulacandin class from Fusarium sambucinum. I. Identity of the producing organism, fermentation and biological activity.

The fuscandins, antifungal agents of the papulacandin class, are produced by a strain of Fusarium sambucinum. Fermentation yielded 60 mg/liter of fusacandin A and minor amounts of fusacandin B. As expected, the fusacandins inhibit (1,3)-beta-glucan synthesis.

Neodymium:yttrium-aluminum-garnet laser fusion of endarterectomy flaps.

Purpose: This study evaluated the efficacy of neodymium:yttrium-aluminum-garnet laser welding of flaps in canine arteries and in securing the distal flap during human carotid endarterectomy.

Methods: Endarterectomy flaps were created in both common carotid and both common femoral arteries in 12 dogs. The flaps were repaired with either the neodymium:yttrium-aluminum-garnet laser or with 6-0 polypropylene sutures.

Further evidence from functional studies for somatostatin receptor heterogeneity in guinea-pig isolated ileum, vas deferens and right atrium.

1. Somatostatin (SRIF) causes a concentration-dependent inhibition of neurotransmission in guinea-pig ileum and vas deferens as well as negative inotropy in guinea-pig isolated right atrium. The SRIF receptors mediating these effects have now been further characterized by use of the peptides BIM-23027, BIM-23056 and L-362855, reported as selective for the recombinant SRIF receptor types, sst2, sst3 and sst5, respectively.