Enhanced expression of cathepsin L in metastatic bone tumors.

Cathepsin L is a kind of cystein proteases which are known to facilitate the invasion and metastasis of tumor cells by degrading the components of basement membrane and extracellular matrix. This study was undertaken to investigate the expression of cathepsin L by Northern blot analysis with radiolabeled cDNA specific for cathepsin L in six normal tissues, two osteosarcoma cell lines, MG-63 and Saos-2, six primary bone tumors and six metastatic bone tumors. In six normal tissues, the highest level of cathepsin L was expressed in liver with the descending order of liver > lung > thymus > ovary > kidney > esophagus. One of the two osteosarcoma cell lines established from the primary sites expressed a high level of cathepsin L mRNA. Out of six primary bone tumors, three (50%) expressed cathepsin L mRNA, while all (100%) of six metastatic bone tumors expressed the mRNA. These results demonstrating the higher frequency of expression of cathepsin L in metastatic bone tumors suggest that cathepsin L may participate in tumor invasion and metastasis.     

Vascular endothelial growth factor receptor signaling is required for cardiac valve formation in zebrafish.

Vascular endothelial growth factor-receptors (VEGF-Rs) are pivotal regulators of vascular development, but a specific role for these receptors in the formation of heart valves has not been identified. We took advantage of small molecule inhibitors of VEGF-R signaling and showed that blocking VEGF-R signaling with receptor selective tyrosine kinase inhibitors, PTK 787 and AAC 787, from 17-21 hr post-fertilization (hpf) in zebrafish embryos resulted in a functional and structural defect in cardiac valve development. Regurgitation of blood between the two chambers of the heart, as well as a loss of cell-restricted expression of the valve differentiation markers notch 1b and bone morphogenetic protein-4 (bmp-4), was readily apparent in treated embryos. In addition, microangiography revealed a loss of a definitive atrioventricular constriction in treated embryos. Taken together, these data demonstrate a novel function for VEGF-Rs in the endocardial endothelium of the developing cardiac valve.     

Use of convalescent plasma therapy in SARS patients in Hong Kong

In order to evaluate the efficacy of convalescent plasma therapy in the treatment of patients with severe acute respiratory syndrome (SARS), 80 SARS patients were given convalescent plasma at Prince of Wales Hospital, Hong Kong, between 20 March and 26 May 2003. Good outcome was defined as discharge by day 22 following the onset of SARS symptoms. Poor outcome was defined as death or hospitalization beyond 22 days. A higher day-22 discharge rate was observed among patients who were given convalescent plasma before day 14 of illness (58.3% vs 15.6%; P<0.001) and among those who were PCR positive and seronegative for coronavirus at the time of plasma infusion (66.7% vs 20%; P=0.001).     

The effects of repeated exposure to anoxia on intracellular calcium,glycogen and lactate in isolated ferret heart muscle

Isolated cardiac tissue from the ferret was repeatedly exposed to anoxia while perfused with glucose-containing Tyrode solution. In one series of experiments, papillary muscles were injected with aequorin to measure intracellular Ca²⁺. On the first exposure to anoxia, the Ca²⁺ transients often increased, but on subsequent exposures this increase disappeared and eventually the Ca²⁺ transients declined on exposure to anoxia. This decline in the Ca²⁺ transients could be converted back to an increase by a 1 h exposure to an elevated (×5) glucose concentration. Exposure of aerobic muscles to 10 mM lactic acid caused a similar increase in the Ca²⁺ transients to that seen in early exposures to anoxia. In a second series of experiments, performed on Langendorff-perfused hearts, measurements were made of glycogen concentration preceding, and lactate production during, exposures to anoxia. At a constant level of glucose, glycogen concentration and lactate production were found to decline on repeated exposures to anoxia, and both were increased after a period of elevated glucose and reduced stimulation frequency. These results suggest that the response of the Ca²⁺ transients to anoxia is dependent on the metabolic status of the muscle. The increase in the Ca²⁺ transients during an early eposure to anoxia may be a consequence of lactic acid production due to accelerated glycolysis. Repeated exposures to anoxia reduce glycogen concentration and lactate production and this reduces the rise in the Ca²⁺ transients.     

Comparison of Gadomer-17 and Gd-DTPA in image quality of contrast-enhanced MR angiographies using flow phantom model

The purpose of this study was to compare the image quality of 3D-TOF MR angiography (MRA) using Gadomer-17 with that using Gd-DTPA in a flow phantom model, and to present preliminary data about the proper dose concentration of Gadomer-17. In the visual analysis of vessel conspicuity, we compared the quality of pre- and post-contrast MIP images. For quantitative analysis, the signal intensities were measured in the axial base 3D-TOF images, and then the relative contrast enhancement was calculated. The results of our studies were that: 1. Maximal signal intensities were obtained at 1 mmol/L of Gadomer-17 and 4 mmol/L of Gd-DTPA. 2. Flow-related signal loss was decreased by Gd-DTPA proportional to the concentration, but Gadomer-17 did not show such a dose accumulative effect. In conclusion, after comparing the results of Gd-DTPA, it was clear that improved MRA images and higher signal intensities of vessels were obtained when lower concentrations of Gadomer-17 were used.     

Integrated medical informatics with small group teaching in medical education

National Taiwan University College of Medicine (NTUCM) introduced small groups of teaching and basic-clinical integrated courses for medical students in 1992. By using computer network and multimedia techniques, this study tried to overcome barriers to learning in small group teaching. The Department of Medical Informatics of NTUCM established campus networking and computer classrooms and provided Internet and intranet network services including mail, netnews, bulletin board systems (BBS), world wide web (WWW), gopher, ftp and local file servers. To implement an interactive learning environment, the authors first tried mail lists, newsgroups and BBS. Next an integrated learning system prototype on the WWW was developed to provide functions including online syllabus, discussion boards simulated to BBS, online talk, interactive case studies, virtual classroom with video on demand (VOD) and Internet medical resources. The results showed that after the medical students completed the required course of medical informatics and had good network access using a network to communicate with each other became a daily practice. In the future, the system will extend to the tutoring of clinical practice and continuing medical education. The authors expect a national medical education network and more international cooperation and exchange.     

Myelin Degeneration in Multiple System Atrophy Detected by Unique Antibodies

A rabbit antiserum (anti-EP), induced against a synthetic peptide corresponding to residues 68 to 86 of guinea pig myelin basic protein, powerfully immunostained abnormal-appearing oligodendrocytic processes and cell bodies in demyelinating areas associated with multiple system atrophy (MSA). However, as we reported previously, the antiserum, which is highly specific for the sequence QDENPVV corresponding to human myelin basic protein residues 82 to 88, failed to recognize any structures in normal human brain. QD-9, a mouse monoclonal antibody raised against human myelin basic protein residues 69 to 88, which also recognizes specifically the epitope QDENPVV, gave the same results as did anti-EP. The unusual epitope recognized by anti-EP/QD-9 antibodies appears to be accessible in areas of myelin degeneration, and the antibodies have been shown to detect such areas in multiple sclerosis and infarcted brains. These antibodies detect myelin degeneration more widely than previous conventional methods. The present study emphasizes the importance of myelin degeneration in the pathogenesis of multiple system atrophy.     

Ventilatory control studied with circulatory occlusion during exercise recovery

Summary Mechanisms involved in the control of pulmonary ventilation were studied in seven male subjects following 6 min of exercise on a cycle ergometer at 98w. Circulation to the legs was occluded by thigh cuffs (27 kPa) during the last 15 s of exercise and the subsequent 4 min of recovery. Respiratory gas exchange and the tidal partial pressures of O₂ and CO₂ were measured breathby-breath. The results were compared to control studies without occlusion. There was a significant increase in both systolic and diastolic blood pressures during occluded recovery. Following occlusion systolic pressure remained elevated while diastolic pressure returned to control values. Occlusion during recovery caused hyperventilation during the first 1.5 min after exercise as evidenced by significantly higher , P_ETO₂, and lower P_ETCO₂. Following the release of the cuffs P_ETCO₂, , and heart rate all increased significantly above control values, while P_ETO₂ decreased. P_ETCO₂ rose abruptly 14.5±0.9 s after the release of the cuffs. Marked increases inV _E and heart rate were seen, and occurred 30.8±1.5 s and 12.8±1.3 s, respectively, after cuff release. The 16.3±1.4 s lag between the increase in P_ETCO₂ and after occlusion suggests that the ventilatory response to a sudden load of hypercapnic blood is not mediated by a pulmonary chemoreceptor. Other receptors, probably the peripheral chemoreceptors, appear to be responsible for hypercapnic hyperventilation.