Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis.

To investigate the relationship between Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), we determined gene expression profiles of discrete pathological stages of esophageal neoplasia using a sequence-verified human cDNA microarray. Fifty one RNAs, comprising 24 normal esophagi (NE), 18 BEs, and nine EACs were hybridized to cDNA microarrays. Five statistical analyses were used for the data analysis. Genes showing significantly different expression levels among the three sample groups were identified. Genes were grouped into functional categories based on the Gene Ontology Consortium. Surprisingly, the expression pattern of BE was significantly more similar to EAC than to NE, notwithstanding the known histopathologic differences between BE and EAC. The pattern of NE was clearly distinct from that of EAC. Thirty-six genes were the most differentially modulated, according to these microarray data, in BE-associated neoplastic progression. Twelve genes were significantly differentially expressed in cancer-associated BE's plus EAC (as a single combined tissue group) vs noncancer-associated BE's. These genes represent potential biomarkers to diagnose EAC at its early stages. Our results demonstrate that molecular events at the transcriptional level in BE are remarkably similar to BE's-associated adenocarcinoma of the esophagus. This finding alarmingly implies that BE is biologically closer to cancer than to normal esophagus, and that the cancer risk of BE is perhaps higher than we had imagined. These findings suggest that changes modulated at the molecular biologic level supervene earlier than histologic changes, and that BE is an early intermediate stage in the process of EAC.

Dopaminergic behaviors and signal transduction mediated through adenylate cyclase and phospholipase C pathways.

We determined the relative effects of chemical receptor inactivation on dopaminergic signaling through adenylate cyclase and phospholipase C pathways and evaluated the behavioral implications of such receptor manipulations. Groups of rats were given intraperitoneal injections of 10 mg/kg N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), a reagent that differentially inactivates neurotransmitter receptors. Control and treated animals were used to assess dopaminergic-mediated behaviors or brain tissues were prepared from the animals and used to assay D1-like receptor binding and agonist-stimulated second messenger formation. EEDQ decreased by 75% the number of D1-like binding sites and completely abolished dopamine-stimulated cyclic AMP formation in striatal membranes. Conversely, dopamine-stimulated phosphoinositide hydrolysis was insensitive to inactivation by EEDQ as examined over different durations of EEDQ treatment, in different brain regions, or with different concentrations of the D1-like receptor agonist SKF38393. EEDQ-pretreated animals lost their stereotypic response to apomorphine but showed increased vacuous jaw movements in response to apomorphine or SKF38393. Basal catalepsy was increased and SCH23390 was unable to further enhance catalepsy beyond the basal levels in the lesioned animals. In naive animals, SCH23390 catalepsy was reversed by apomorphine, and apomorphine stereotypy was reversed by SCH23390. Taken together, the present results imply that the dopamine-sensitive phospholipase C system mediates a subset of dopaminergic behaviors, notably vacuous jaw movements, in contrast to stereotypy and catalepsy which appear to be respectively mediated through stimulation and inhibition of the adenylate cyclase-coupled dopaminergic system.

Developmental expression of glycine immunoreactivity and its colocalization with GABA in the embryonic chick lumbosacral spinal cord.

The development of immunoreactivity for the putative inhibitory amino acid neurotransmitter glycine was investigated in the embryonic and posthatched chick lumbosacral spinal cord by using postembedding immunocytochemical methods. Glycine immunoreactive perikarya were first observed at embryonic day 8 (E8) both in the dorsal and ventral gray matters. The number of immunostained neurons sharply increased by E10 and was gradually augmented further at later developmental stages. The general pattern of glycine immunoreactivity characteristic of mature animals had been achieved by E12 and was only slightly altered afterward. Most of the immunostained neurons were located in the presumptive deep dorsal horn (laminae IV-VI) and lamina VII, although glycine-immunoreactive neurons were scattered throughout the entire extent of the spinal gray matter. By using some of our previously obtained and published data concerning the development of gamma-aminobutyric acid (GABA)-ergic neurons in the embryonic chick lumbosacral spinal cord, we have compared the numbers, sizes, and distribution of glycine- and GABA-immunoreactive spinal neurons at various developmental stages and found the following marked differences in the developmental characteristics of these two populations of putative inhibitory interneurons. (i) GABA immunoreactivity was expressed very early (E4), whereas immunoreactivity for glycine appeared relatively late (E8) in embryonic development. (ii) In the ventral horn, GABA immunoreactivity declined, whereas immunoreactivity for glycine gradually increased from E8 onward in such a manner that the sum of glycinergic and GABAergic perikarya remained constant during the second half of embryonic development. (iii) Glycinergic and GABAergic neurons showed different distribution patterns in the spinal gray matter throughout the entire course of embryogenesis as well as in the posthatched animal. When investigating the colocalization of glycine and GABA immunoreactivities, perikarya immunostained for both amino acids were revealed at all developmental stages from E8 onward, and the proportions of glycine- and GABA-immunoreactive neurons that were also immunostained for the other amino acid were remarkably constant during development. The characteristic features of the development of the investigated putative inhibitory spinal interneurons are discussed and correlated with previous neuroanatomical and physiological studies.

Development of specific populations of interneurons in the ventral horn of the embryonic chick lumbosacral spinal cord.

The development, morphological and neurochemical properties of specific populations of interneurons were investigated in the ventral horn of the embryonic and mature chick lumbosacral spinal cord by using pre- and post-embedding immunocytochemical as well as anterograde axonal tracing techniques. We have identified and traced the morphological maturation of the following cell groups: (1) Neurons immunoreactive for calbindin-D 28k (CaB), a calcium-binding protein that has been reported to be a marker of certain subsets of excitatory spinal neurons. We have distinguished and traced the maturation of three CaB-immunoreactive cell groups in the ventral horn; (2) Neurons immunoreactive for GABA and glycine, the two putative inhibitory amino acid neurotransmitters in the spinal cord; (3) Neurons within the nucleus marginalis, a cell group located in the ventrolateral aspect of the white matter in close proximity to the lateral motor column. The characteristic features of the development of these neurons are discussed and correlated with previous neuroanatomical and physiological studies concerning motor functions in the developing chick spinal cord.

Developmental changes in the distribution of gamma-aminobutyric acid-immunoreactive neurons in the embryonic chick lumbosacral spinal cord.

The development of gamma-aminobutyric acid (GABA)-immunoreactive neurons was investigated in the embryonic and posthatch chick lumbosacral spinal cord by using pre- and postembedding immunostaining with an anti-GABA antiserum. The first GABA-immunoreactive cells were detected in the ventral one-half of the spinal cord dorsal to the lateral motor column at E4. GABAergic neurons in this location sharply increased in number and, with the exception of the lateral motor column, appeared throughout the entire extent of the ventral one-half of the spinal gray matter by E6. Thereafter, GABA-immunoreactive neurons extended from ventral to dorsal regions. Stained perikarya first appeared at E8 and then progressively accumulated in the dorsal horn, while immunoreactive neurons gradually declined in the ventral horn. The general pattern of GABA immunoreactivity characteristic of mature animals had been achieved by E12 and was only slightly altered afterwards. In the dorsal horn, most of the stained neurons were observed in laminae I-III, both at the upper (LS 1-3) and at the lower (LS 5-7) segments of the lumbosacral spinal cord. In the ventral horn, the upper and lower lumbosacral segments showed marked differences in the distribution of stained perikarya. GABAergic neurons were scattered in a relatively large region dorsomedial to the lateral motor column at the level of the upper lumbosacral segments, whereas they were confined to the dorsalmost region of lamina VII at the lower segments. The early expression of GABA immunoreactivity may indicate a trophic and synaptogenetic role for GABA in early phases of spinal cord development.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of subacute bacterial endocarditis related to Alcaligenes faecalis]. / Alcalgenes faecalis'e bagli subakut bakteriyel endokardit olgusu.

Alcaligenes faecalis was isolated from the blood culture of an 18 years old patient with subacute bacterial endocarditis and rheumatic valvular disease. Isolated strain agglutinated with patient's serum at a ratio of 1/160.