ABSTRACT
Mucosal Schwann cell hamartoma (MSCH) is an uncommon neural lesion characterized by an ill-defined proliferation of S100-positive Schwann cells in the lamina propria, with reported cases exclusively occurring in the colorectum. Here we describe the first series of MSCHs arising in the gastroesophageal junction (GEJ) and discuss their clinicopathologic features in comparison with their colorectal counterparts. We searched the UCLA pathology database from 01/2014 to 12/2018 to identify cases carrying the diagnosis of MSCH. A total of 48 cases (45 in-house, 3 consults) of colorectal MSCHs and 6 cases (1 in-house, 5 consults) of GEJ MSCHs were identified. For GEJ MSCHs, there were 4 males and 2 females with an average age of 70.2 years (range: 57-76 years). Clinical indications for endoscopy included history of gastroesophageal reflux disease (n = 2), heartburn (n = 2), dysphagia (n = 1), and iron deficiency anemia (n = 1). Endoscopic findings at the GEJ were available for 5 patients including irregular Z-line (n = 3), mild nodular carditis (n = 1), and normal (n = 1). None of them showed a polyp or nodule. The mean size of the lesion was 2.8 mm (range: 2-4 mm) microscopically. None of the colorectal or GEJ MSCH cases had an association with inherited syndromes. In conclusion, MSCH of the gastrointestinal tract is predominantly seen in the colorectum, but also infrequently seen in the GEJ. GEJ MSCH shares histologic and immunohistochemical features with its colorectal counterpart, but is usually an incidental finding with no endoscopically visible lesion. As there is no syndromic association with MSCH, additional treatment, work-up and follow-up are unnecessary.
Subject(s)
Esophagogastric Junction/pathology , Hamartoma/diagnosis , Mucous Membrane/pathology , Schwann Cells/pathology , Aged , Colon/innervation , Colon/pathology , Colorectal Neoplasms/pathology , Diagnosis, Differential , Endoscopy, Digestive System/standards , Endoscopy, Digestive System/statistics & numerical data , Esophagogastric Junction/diagnostic imaging , Esophagogastric Junction/innervation , Female , Hamartoma/pathology , Humans , Incidental Findings , Male , Middle Aged , Mucous Membrane/innervation , Rectum/innervation , Rectum/pathology , S100 Proteins/metabolism , Schwann Cells/metabolismSubject(s)
Climate Change , Earth, Planet , Fossil Fuels/statistics & numerical data , Hot Temperature , HumansABSTRACT
A convergent synthesis route for the heterocyclic modification of a novel bicyclo[3.1.0]hexane NPY1 antagonist 2 was developed and the structure activity relationship of these modifications on NPY1 binding is reported. Two heterocyclic analogs 9 and 10 showed comparable Y1 binding potency to 2, but with improved aqueous solubility. Compound 9 demonstrated reduced spontaneous nocturnal food intake in a rat model when dosed ip. Compound 9 was also shown to be orally bioavailable and brain penetrable.
Subject(s)
Bridged Bicyclo Compounds/pharmacology , Heterocyclic Compounds/pharmacology , Receptors, Neuropeptide Y/antagonists & inhibitors , Administration, Oral , Animals , Bridged Bicyclo Compounds/administration & dosage , Bridged Bicyclo Compounds/chemistry , Dose-Response Relationship, Drug , Heterocyclic Compounds/administration & dosage , Heterocyclic Compounds/chemistry , Male , Molecular Structure , Rats , Rats, Sprague-Dawley , Structure-Activity RelationshipABSTRACT
A novel class of bicyclo[3.1.0]hexanylpiperazine neuropeptide Y (NPY) Y1 antagonists has been designed and synthesized. Scatchard binding analysis showed these compounds to be noncompetitive with [(125)I]PYY binding to the Y1 receptor. The most potent member, 1-((1α,3α,5α,6ß)-6-(3-ethoxyphenyl)-3-methylbicyclo[3.1.0]hexan-6-yl)-4-phenylpiperazine (2) had an IC50 = 62 nM and displayed excellent oral bioavailability in rat (% F po = 80), as well as good brain penetration (B/P ratio = 0.61). In a spontaneous nocturnal feeding study with male Sprague-Dawley rats, 2 significantly reduced food intake during a 12 h period.
ABSTRACT
A series of novel 5,5-diphenylimidazolones was synthesized and evaluated for activity against the human neuropeptide Y5 receptor. The 3-pyridyl analog 46 demonstrated an IC(50) of 8.3 nM with a favorable pharmacokinetic profile in rats, but was ineffective in reducing food intake.
Subject(s)
Anti-Obesity Agents/pharmacology , Eating/drug effects , Imidazoles/pharmacology , Receptors, Neuropeptide Y/antagonists & inhibitors , Animals , Anti-Obesity Agents/chemical synthesis , Humans , Imidazoles/chemical synthesis , Inhibitory Concentration 50 , Radioligand Assay , Rats , Rats, Sprague-Dawley , Receptors, Neuropeptide Y/metabolism , Structure-Activity Relationship , Time FactorsABSTRACT
In an era of increasing resistance to classical antibacterial agents, the synthetic oxazolidinone series of antibiotics has attracted much interest. Zyvoxtrade mark was the first oxazolidinone to be approved for clinical use against infections caused by multi-drug resistant Gram-positive bacteria. In the course of studies directed toward the discovery of novel antibacterial agents, a new series of synthetic phenyl-isoxazolinone agents that displayed potent activity against Gram-positive bacterial strains was recently discovered at Bristol-Myers Squibb. Extensive investigation of various substitutions on the phenyl ring was then undertaken. We report here, the synthesis and antibacterial activity of a series of biaryl isoxazolinone compounds.
