INCREASED IN VITRO RADIO-SENSITIVITY OF MALGNANT MELANOMA INDUCED BY THE IN VIVO ADMINISTRATION OF CHLORPROMAZINE

Summary.— In vitro x-ray irradiation with 3000 R of strips of Fortner's melanotic melanoma was found to have no effect on the rate of successful transplantation of these strips in hamsters. However, when the hamsters bearing; the melanomata from which the strips were obtained had been treated with 3·5 mg chlorpromazine before irradiation, the incidence of melanoma transplantability was reduced to 33%. Chlorpromazine-treated melanomata which did grow after irradiation grew at a greatly reduced rate. It is postulated that chlorpromazine may increase the radio-sensitivity of melanized cells by masking the free radical nature of melanin.     

MEDIASTINAL EMPHYSEMA AFTER ESOPHAGEAL ENDOSCOPIC SUBMUCOSAL DISSECTION: ITS PREVALENCE AND CLINICAL SIGNIFICANCE

Aims: To assess the prevalence and clinical significance of mediastinal emphysema (ME) after esophageal endoscopic submucosal dissection (ESD). Methods: A total of 105 patients in whom assessment of ME was prospectively carried out with multi‐detector row computed tomography (MDCT) after esophageal ESD were included in this study. ME was graded as follows: Grade‐0, no ME; Grade‐I, bubbles around the esophagus; Grade‐II, ME around the thoracic aorta; Grade‐III, ME extending around the heart or beyond the mediastinum into the neck; and Grade‐IV, ME with pneumothorax or subcutaneous emphysema. MDCT grading was compared with the finding of conventional chest X‐ray images (CXR) and clinical symptoms. Results: CXR revealed the presence of ME in 6.6% of the subjects. On MDCT, ME was recognized in 62.9% (Grade‐0, 37.1%; I, 46.7%; II, 10.5%; III, 5.7%; and IV, 0%), most (83.8%) being Grade‐I or 0. CXR was able to visualize ME of Grade‐II or greater. Exposure of the muscularis propria layer and location of the lesion were significant risk factors for development of ME of Grade‐II or greater (P = 0.008 and P = 0.03, respectively). The duration of a fever of 37°C or higher was longer and the serum C‐reactive protein level was higher in patients with a higher grade of ME. Conclusions: MDCT revealed the occurrence of ME in 62.9% of the patients who had undergone esophageal ESD, most of which, however, was clinically silent. Exposure of the muscular layer during ESD and location of the lesion were independent risk factors for the development of ME.     

HSP-derived Peptides Inducing Uveitis and IgG and IgA Antibodies

Heat shock protein (HSP) 65 kD-derived peptides, which specifically stimulate T cells from patients with Behçet's disease (BD), are capable of inducing uveitis in rats. Mycobacterial HSP 65 kD and BD-specific peptides were injected into Lewis rats and the development of uveitis was monitored clinically and histologically, and IgG and IgA antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Rats immunized with HSP peptides that developed uveitis showed significantly higher serum IgG antibody levels to peptide 311–326 (P<0.05) and the corresponding homologous human peptide 336–351 (P<0.01) than rats without uveitis. Significant increases in serum IgA antibodies in rats with uveitis were also observed in those immunized with peptides 111–125, 311–326 and 336–351 (P<0.05). Rats injected with HSP 65 kD showed a rise in IgG antibody levels to peptides 111–125, 154–172 and 311–326 and to a lesser extent, a rise in IgA antibody level to peptide 311–326. HSP showed almost complete inhibition of binding of IgG antibodies to HSP 65 kD, but peptides 111–125, 154–172, 311–326 and 336–351 showed inhibition to a lesser extent in a competitive assay. These results suggest that increases in IgG and IgA antibody levels to specific peptides within HSP, develop in rats with uveitis. The T and B cell epitopes responsible for the development of ocular disease in rats immunized with HSP-derived peptides, appear to be similar or identical to those found in patients with the ocular type of BD.     

Optimal Pacemaker Sensing with Respect to Amplitude and Slew Rate of Intracardiac Electrograms: Theoretical Analysis by Computer Simulation

The optimal amplitude and slew rate of intracardiac electrograms for pacemaker sensing Here examined on a theoretical basis by computer simulation. The simulation was based on the concept that it is the voltage at the position of the pacing electrode in an electrical field of a moving electrical dipole. By changing the distance between the electrode and the myocardium and the moving velocity of the electrical dipole, simulated ECGs with arbitrary amplitudes and slew rates were generated by the computer and fed to a bandpass filter. This filter was equivalent to those assembled in some models of permanent pacemakers and had a center pass-band frequency of 50 Hz and a Q of 1.0. The outputs of the filter were measured. The results showed that, for pacemaker sensing, simulated intracardiac electrograms with high amplitude should have high slew rates and those with low amplitudes should have low slew rates, although the absolute values depend on the characteristics of the bandpass filter and the sensing threshold of the pacemaker.     

Hypercalcemia associated with Aeromonas hydrophila gastro-enteritis

We describe a 4 year old girl with acute Aeromonas hydrophila gastro-enteritis who presented with a combination of hypercalcemia, metabolic alkalosis, and renal impairment. Serum parathyroid hormone was not elevated. Both milk-alkali syndrome and intoxication of vitamins A and D were ruled out. The hypercalcemia, metabolic alkalosis, and renal impairment were improved by fluid infusion and intravenous administration of furosemide. Gastro-enteritis also improved with oral administration of the antibiotic norfloxacin. The association of A. hydrophila gastro-enteritis with hypercalcemia has not been described previously.     

Cardiac Pacing in Fetal Lambs: Intrauterine Transvenous Cardiac Pacing for Fetal Complete Heart Block

To evaluate the feasibility of intrauterine transvenous cardiac pacing, the right ventricular output was measured during pacing in six fetal lambs. Under maternal anesthesia, the uterus was opened, and, under local anesthesia, the pacing lead (Medtronic Capsure SP4023) was inserted via the fetal left internal jugular vein. Right ventricular output was estimated using an Aloka SSD-730 ultrasound device, and tricuspid valve regurgitation was evaluated with an Aloka SSD-880 using the transuterine approach. The ultrasonic right ventricular cardiac output was measured under three different conditions: (1) with the tip of the pacing lead in the superior vena cava (control); (2) with the tip of the pacing lead in the right ventricle; and (3) with pacing at 200 beats/min. The right ventricular output decreased when the pacing lead was inserted into the right ventricle, as well as during pacing at 200 beats/min ([1] = 107 ± 13.2 ml/kg per min; [2] = 73.8 ± 17. 5 ml/kg per min; and [3] = 78.3 ± 23.6 ml/kg per min), Tricuspid regurgitation did not change under any of the conditions tested. Intrauterine transvenous cardiac pacing was successfully achieved. Insertion of the pacing lead into the right ventricle decreased the ventricular output without increasing tricuspid valve regurgitation.     

Involvement of growth factor receptor-bound protein-2 in rat hepatocyte growth

Growth factor receptor-bound protein-2 (GRB-2) is a protein linking receptor tyrosine kinase and Sos ( Son of Sevenless gene; Ras GDP/GTP exchange protein), leading to activation of the Ras-mitogen-activated protein kinase (MAPK) cascade. So far, it remains unclear how GRB-2 plays a role in signal transduction pathways evoked by hepatotrophic factors. This study was attempted to evaluate the involvement of GRB-2 in signalling in rat hepatocyte growth. Using rat cultured hepatocytes stimulated by hepatotrophic factors and regenerating livers after partial hepatectomy (PH) we examined GRB-2-mediated linkage of hepatotrophic factor receptors to signal transducing molecules such as Sos or dynamin-II by immunoprecipitation and western blot analysis. In primary cultured hepatocytes stimulated with hepatocyte growth factor (HGF) or epidermal growth factor (EGF), GRB-2 linked HGF receptor or EGF receptor, respectively, to Sos which activated the mitogen-activated protein kinase (MAPK) cascade. In contrast, in primary cultured hepatocytes stimulated with insulin, GRB-2 linked insulin receptor substrate-1 (IRS-1) to dynamin-II as well as Sos. In the early phase after PH, GRB-2 activated the Ras-MAPK cascade by linking HGF receptor, IRS-1, or EGF receptor to Sos. In the late phase after PH, a complex of IRS-1-GRB-2 associated with dynamin-II, indicating that GRB-2 may transduce signals from IRS-1 to dynamin-II. We conclude that GRB-2 may play a role in transmitting signals from hepatotrophic factors to not only MAPK but also to other signalling pathways in hepatocyte growth.