Alternative splicing in fibroblast growth factor receptor 2 is associated with induced epithelial-mesenchymal transition in rat bladder carcinoma cells

We described previously that acidic fibroblast growth factor (aFGF), but not basic fibroblast growth factor (bFGF), can induce the rat carcinoma cell line NBT-II to undergo a rapid and reversible transition from epithelial to mesenchymal phenotype (EMT). We now find that NBT-II EMT is stimulated by keratinocyte growth factor (KGF) in cells grown at low density. Accordingly, a high-affinity receptor showing 98% homology to mouse FGF receptor 2b/KGF receptor was cloned and sequenced from NBT-II cells. Northern analysis indicated that mRNA for FGF receptor 2b/KGF receptor was drastically down-regulated within 1 wk in aFGF-induced mesenchymal NBT-II cells. This decrease coincided with an up-regulation of FGF receptor 2c/Bek, a KGF-insensitive, alternatively spliced form of FGF receptor 2b/KGF receptor. Functional studies confirmed that KGF could not maintain EMT induction on mesenchymal NBT-II cells. FGF receptor 1 and FGF receptor 2c/Bek could also support EMT induction when transfected into NBT-II cells in response to aFGF or bFGF. Such transfected cells could bind bFGF as well as aFGF. Therefore, EMT can be induced through different FGF receptors, but EMT may also regulate FGF receptor expression itself.     

Therapy of multidrug-resistant typhoid fever with oral cefixime vs. intravenous ceftriaxone

We randomly allocated 80 children with suspected multidrug-resistant tyhpoid fever to therapy with either cefixime or ceftriaxone. Of these, an alternative diagnosis was subsequently made in 10 children and another 10 were excluded because cultures were negative. In 9 cases the typhoidal organisms isolated were susceptible to first-line drugs. In all, 50 children were randomly allocated to receive therapy with either intravenous ceftriaxone (65 mg/kg/day once daily, Group A, n = 25) or oral cefixime (10 mg/kg/day divided every 12 hours, Group B, n = 25) for 14 days. The two groups were comparable in their clinical characteristics, duration and severity of illness at the time of admission. The time to defervescence was comparable in both groups (8.3 +/- 3.7 vs. 8.0 +/- 4.1 days, P = not significant). An equal number (3 in each group) failed to respond and underwent a change in therapy. Three children in Group A and one in Group B relapsed. No adverse effects were seen in either group during the course of therapy. Our data suggest that oral cefixime can be used as effectively as parenterally administered ceftriaxone for management of typhoid fever in children.     

Comparative effects of atenolol versus celiprolol on serum lipids and blood pressure in hyperlipidemic and hypertensive subjects

Antihypertensive drugs may affect serum lipoprotein levels in mixed populations but data in hyperlipidemic patients are scanty. Atenolol versus celiprolol effects on serum lipoproteins were compared in 159 hyperlipoproteinemic hypertensive patients. This was a randomized, double-blind, parallel-group, positive-controlled multicenter trial with centralized lipoprotein laboratory and diet constancy monitoring. Blood pressure reduction and serum lipoprotein and apoprotein levels were monitored for 3 months. Both drugs reduced systolic and diastolic blood pressures. Atenolol had greater effects than celiprolol on diastolic pressure, but effects on systolic blood pressure were not different. Patients receiving atenolol had lower serum high-density lipoprotein cholesterol levels and higher low-density lipoprotein/high-density lipoprotein cholesterol ratios, whereas patients treated with celiprolol showed no contrasting changes. These differences in lipoprotein levels between drug treatment groups were statistically significant at weeks 9 and 12. The difference between drug treatments was also significant if the values of the 9- and 12-week visits were averaged. Patients taking atenolol had statistically significantly higher serum levels of total cholesterol, triglycerides and apoprotein B at 9 weeks. These divergent directional changes were consistent throughout and statistically significantly different between drugs.     

Identification of the chromosome 14 origin of a C-negative marker associated with a 14q32 deletion by chromosome painting

A constitutional chromosome 14 rearrangement was observed in a female with a psychodevelopmental disorder. Karyotype analysis using a variety of chromosome techniques, QFQ, GTG, CBG, Ag-NOR and DA-DAPI, showed a deletion of chromosome 14q32.1-qter region in association with a supernumerary marker chromosome. The marker, resembling a submetacentric, approximately half the size of a G group chromosome is C band and Ag-NOR negative. The heteromorphism of the satellites showed that the deleted chromosome 14 is paternal in origin. Chromosome painting using an Alu-PCR probe specific for the human chromosome 14 and fluorescent in situ hybridization (FISH) showed that the marker contains chromosome 14q32 sequences. It is likely that the marker was generated from the deleted chromosome 14 region through a complex rearrangement.     

Effect of aluminum hydroxide/magnesium hydroxide antacid and bismuth subsalicylate on gastric pH in horses

OBJECTIVE: To assess the effect of aluminum hydroxide/magnesium hydroxide antacid and bismuth subsalicylate on gastric pH in clinically normal horses and to develop guidelines on the use of these agents for treatment of peptic ulcer disease in horses. DESIGN: Prospective, randomized, controlled trial. ANIMALS: 5 clinically normal adult horses with chronically implanted gastric cannulas. PROCEDURE: Each horse received all 5 treatments (30 g of aluminum hydroxide/15 g of magnesium hydroxide, 12 g of aluminum hydroxide/6 g of magnesium hydroxide, 10.5 g of bismuth subsalicylate, 26.25 g of bismuth subsalicylate, and 5% methylcellulose control) with only 1 experiment performed each day. Gastric pH was measured via a glass electrode inserted through the gastric cannula for 1 hour before treatment and continued for 2 hours after treatment. Food or water was not given to the horses during the experiment. Measurements of gastric pH obtained during posttreatment hours were compared with pretreatment gastric pH values. RESULTS: Only a dose of 30 g of aluminum hydroxide/ 15 g of magnesium hydroxide resulted in a significant increase in gastric pH over baseline or control values. Mean pH was 5.2 +/- 0.62 and 4.59 +/- 0.48 for posttreatment hours 1 and 2, respectively. CLINICAL IMPLICATIONS: Oral administration of 30 g of aluminum hydroxide/15 g of magnesium hydroxide to adult horses should result in a mean hourly gastric pH > or = 4.0 for at least 2 hours.     

Endoscopic management of biliary fistula

A 78-year-old woman complained of ocular pain in the right eye. Thirty-three months before, the patient had a pterygium excised and mitomycin C, 0.04%, was instilled 3 times a day postoperatively for 10 days in the right eye. The same surgery was performed and the same drug was used for a course of 5 days in the left eye. Corneoscleral ulceration and corneal performation occurred in the right eye. The lesions were successfully treated with a lamellar patch graft with reserved corneosclera. We believe that it may not be safe to instill 0.04% mitomycin C 3 times a day postoperatively for 10 days.