Expression of c-erbB-2 protein in keratinocytes of oral mucosal lichen planus and subsequent squamous cell carcinoma

Oral mucosal lichen planus (OMLP) is a well recognized mucosal disease with unknown etiology. Considerable controversy exists as to whether OMLP is intrinsically premalignant, or if the disorder facilitates the development of oral mucosal squamous cell carcinoma (OMSCC) by external factors. The aim of the present study was to investigate the expression of c-erbB-2 protein in the keratinocytes of initial biopsies of oral mucosal disorders diagnosed as OMLP with no evidence of epithelial dysplasia. and to compare the results with the expression of c-erbB-2 protein in subsequent biopsies obtained from the same patients. These results were compared with the findings from control groups (patients with dysplasia with no evidence of OMLP, patients with OMSCC with no evidence of OMLP and normal oral mucosa). The expression of the c-erbB-2 protein was evaluated by immunohistochemical staining of the gene product with the avidin-biotin-complex method using paraffin-embedded tissue sections. Five of the initial biopsies from patients with OMLP expressed the c-erhB-2 protein and one did not. None of the OMLP cases that subsequently showed evidence of dysplasia expressed the c-erhB-2 protein, and of the three OMSCC specimens from the patients with OMLP. two were negative and one expressed c-erbB-2 protein. The specimens from the control groups all expressed the c-erhB-2 protein. The results indicated the probability of the absence of c-erbB-2 staining being an indication of a potential for neoplastic transformation in OMLP with dysplastic changes.     

Low sodium content formula for infants with congestive heart failure

Twenty-two infants of isolated ventricular septal defect with congestive heart failure were fed with lower-sodium content formula-Lonalac (Mead-Johnson) to study the clinical response of treatment for congestive heart failure. There were no significant changes of intake, urinary output, serum sodium, potassium and osmolality before, 2 days and 6 days after Lonalac feeding. The low sodium content formula may feed the infants with congestive heart failure in addition to the traditional anticongestive therapy.     

Novel benzamides as selective and potent gastric prokinetic agents. 1. Synthesis and structure-activity relationships of N-[(2-morpholinyl)alkyl]benzamides

With the purpose of obtaining more potent and selective gastric prokinetic than metoclopramide (1), a new series of N-[(2-morpholinyl)alkyl]benzamides (17-52) were synthesized and their gastric prokinetic activity was evaluated by determining effects on the gastric emptying of phenol red semisolid meal and of resin pellets solid meal in rats and mice. The morpholinyl moiety was newly designed after consideration of the side-chain structure of cisapride (2) and produced the desired activity when coupled with the 4-amino-5-chloro-2-methoxybenzoyl group of both metoclopramide and cisapride. Modification of the substituents of the benzoyl group markedly influenced the activity. In particular, 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5-chloro-2-methoxybenzamide (17) and the 4-(dimethylamino) and 2-ethoxy analogues (25 and 29) of 17 showed potent and selective gastric prokinetic activity along with a weak dopamine D2 receptor antagonistic activity.     

FR112123, a new oligopeptide antibiotic from Streptomyces viridochromogenes. Taxonomy, fermentation, isolation, physico-chemical properties, structure and biological activity

FR112123 is a new oligopeptide antibiotic produced by Streptomyces viridochromogenes No. 7587. The structure of FR112123 is elucidated as N-(N6-(N2-glycyl-L-glutaminyl)-D-lysyl)-D-alanine (1) by spectroscopic and chemical evidence. It resembles a partial structure of peptidoglycan in bacteria. The compound has a superior activity against an Escherichia coli mutant sensitive to inhibitors of cell wall synthesis, although it has a weak activity against the parent strain. These suggest that FR112123 might act on the biosynthesis of bacterial cell wall.     

Chronic haloperidol and chlorpromazine treatment alters in vitro beta-endorphin metabolism in rat brain

To determine if chronic haloperidol (3.0 mg/kg per day) or chlorpromazine (4.2 mg/kg per day) treatment alters central beta-endorphin metabolism, haloperidol and chlorpromazine were perfused via Alzet minipumps into male Sprague-Dawley rats for 8 days. Crude twice-washed membranes, purified synaptic plasma membranes and Golgi-enriched membranes, respectively, were isolated from rat brains and time course incubated with beta-endorphin. All samples were analyzed by high resolution, reversed-phase high performance liquid chromatography. The half-lives of beta-endorphin for animals treated with haloperidol or chlorpromazine were not statistically different from control animals at the crude washed membranes. At the purified synaptic plasma membranes, however, the half-lives of beta-endorphin from haloperidol (t 1/2 = 45.1 min)- and chlorpromazine (t1/2 = 47.0 min)-treated animals were significantly decreased as compared to the control animals (t1/2 = 78.0 min). The half-life of beta-endorphin at the Golgi-enriched membranes was increased for haloperidol (t1/2 = 112.3 min) and chlorpromazine (t1/2 = 103.0 min)-treated animals when compared to control animals (t1/2 = 80.2 min). The findings indicate a differential effect of the dopamine receptor antagonists haloperidol and chlorpromazine on the extracellular fate at the synaptic plasma membranes of beta-endorphin and the intracellular processing at the Golgi-enriched membranes in vitro.     

Influence of ouabain on the tracheal musculature of the dog

The effects of ouabain on the smooth muscles of the airway were investigated in anesthetized, paralyzed and artificially ventilated mongrel dogs. Ouabain (30 micrograms/kg, i.v.) caused a constriction of the tracheal smooth muscle which was followed by bradycardia. When ouabain was infused at a rate of 2 micrograms/kg/min (i.v.), the tracheal constriction was induced by a total dose of 45.0 +/- 5.5 micrograms/kg, while the bradycardia appeared with a total dose of 54.4 +/- 6.1 micrograms/kg. The ouabain-induced tracheal constriction was inhibited by bilateral vagotomy. The tracheal constriction induced by i.a. infusion of 10 microM ouabain into the bilateral cranial thyroid arteries was inhibited by bilateral vagotomy, but it was not completely blocked. With bilateral vagotomy, the tracheal constriction induced by i.a. infusion of ouabain was unaffected by 3 microM hexamethonium, but it was significantly inhibited by 1 microM atropine. These results suggest that ouabain may induce tracheal constriction by a neurogenic action in addition to its action via the augmentation of the vagal reflex, and the neurogenic action of ouabain may be related, in large part, to the release of acetylcholine from the presynapses of vagus nerves in dogs.     

Synthesis and pharmacological evaluation of a series of dibenzo[a,d]cycloalkenimines as N-methyl-D-aspartate antagonists.

A series of 73 dibenzo[a,d]cycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]-(+)-10) from its specific binding site on rat cortical membranes. A number of the more active compounds (Ki ranging from 0.006 to 0.21 microM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 microM) and anticonvulsant activity in the mouse against NMDA induced convulsions. The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination. In the dibenzo[a,d]cyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher levels of biological activity. While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested.