Chymase participates in chronic dermatitis by inducing eosinophil infiltration

An epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) to a mouse ear caused a transient skin swelling, and the repetition of the challenge enlarged the contact dermatitis. The repeated challenge with DNFB also induced eosinophil infiltration on the application site. Administration of a chymase inhibitor significantly inhibited the ear swelling as well as eosinophil accumulation. An intradermal injection of human chymase to the mouse ear also elicited transient skin swelling and eosinophil infiltration, both of which were augmented in proportion to the number of injections. Human serum albumin and heat-inactivated chymase failed to induce such skin reactions, suggesting the participation of proteolytic activity of the enzyme. In addition, chymase stimulated eosinophil migration in vitro in a concentration-dependent manner. Taken together, these observations suggest that mast cell chymase may contribute to development of the DNFB-induced dermatitis, probably by promoting eosinophil infiltration. It is therefore possible that chymase plays a role in pathogenesis of chronic dermatitis such as atopic dermatitis.     

Evidence in patients with systemic lupus erythematosus of the presence of antibodies against RNA-dependent DNA polymerase of baboon endogenous virus.

Immunoglobulin G (IgG) in six out of 30 patients with systemic lupus erythematosus (SLE) strongly inhibited the activity of RNA-dependent DNA polymerase (RDPase) of baboon endogenous virus, M7, while IgG obtained from scleroderma patients, rheumatoid arthritis patients and normal subjects was less reactive. Experiments with anti-human IgG and with IgG F (ab')2-bound immunoaffinity columns indicated that the inhibition of RDPase was antibody-mediated. The RDPase inhibiting activity of SLE IgG was considered not to be due to cross-reactions of anti-nuclear antibodies including anti-DNA, anti-ribonucleoprotein, anti-Sm and anti-SS.B antibodies. SLE IgG preferably inhibited the RDPase activity of baboon endogenous virus and a feline endogenous virus, RD114. These findings support the hypothesis that retrovirus(es) might be involved in SLE.     

Efficacy of early use of continuous isoproterenol inhalation therapy for severe asthma attacks in children]

The aim of this study was to evaluate the efficacy and safety of continuous isoproterenol inhalation therapy for asthma attacks in children. We used l-body isoproterenol (Proternol L) in 22 children with 32 episodes of severe attacks. One of them did not respond to this therapy, and two had complications (atelectasis and pneumothorax). Twenty-nine cases were divided into three subgroups according to their clinical scores; A) scores less than or equal to 4, which meant that they were in the early stage of severe attack (n = 9), B) scores 5-6, which meant impending respiratory failure (n = 17), C) scores greater than or equal to 7, which meant respiratory failure (n = 3). The values of SpO2 at the start of this therapy were 94.8, 91.5, 82.0%, respectively. The more severe their attacks were, the lower their SpO2 levels were. The periods until their scores became zero were 0.78, 6.3, 17.2 hours, respectively. There were significant differences between each period respectively (p less than 0.001, p less than 0.01). Heart rates decreased when their symptoms improved, and other adverse effects were not detected. These results suggest that this therapy is effective and safe for children with severe asthma attacks, especially in the early stage.     

Early degeneration of the epithelial cells in the initial segment of the epididymal duct in mice after efferent duct cutting

Mouse epididymides were examined by light and electron microscopy 6, 12, 24 h, 1.5, 2, 3, and 5 days after efferent duct cutting when the mice were 60 days of age. Six hours after operation, the principal cells in the initial segment of the epididymal duct began to degenerate following the disappearance of intraluminal spermatozoa. The degenerated cells increased rapidly and reached their greatest number 24 h, and then decreased to smaller numbers until 48 h. These degenerative changes were followed by the appearance of macrophages in the epithelium, which were first seen 12 h after operation, becoming very frequent at one and 1.5 days, and then decreasing to become rare at 3 and 5 days. The macrophages phagocytosed the degenerated principal cells. The degenerated principal cells were also ingested and digested by undegenerated principal cells and basal cells. The intraepithelial mitotic figures had almost disappeared at 24 h but were frequently observed at 2 days and more so at 3 days. They returned to normal numbers at 5 days. The volume of the initial segment was decreased to one third until the third day. The principal cells in this segment became similar in both light-microscopic appearance and ultrastructures to the cells in the next segment 5 days after efferent duct cutting. The changes were localized only in the initial segment.     

Role of KCNQ1 in the cell swelling-induced enhancement of the slowly activating delayed rectifier K(+) current

Cell swelling enhances a slowly activating delayed rectifier K(+) current (I(Ks)) in cardiac cells. This investigation was undertaken to determine which of the two structural units reconstituting the I(Ks) channel, KCNQ1 (KvLQT1) and KCNE1 (minK/IsK), plays a key role in the cell swelling-induced I(Ks) enhancement and to dissect a possible involvement of tyrosine phosphorylation therein. KCNQ1 was transiently expressed alone or together with KCNE1 in a heterologous mammalian cell line. Two distinct whole-cell membrane currents were separately observed during the exposure of transfected cells to various degrees of hyposmotic solutions. A hyposmotic challenge (0.7 times control osmolarity) resulted in about a twofold increase not only in the heteromeric KCNQ1/KCNE1, but also in the homomeric KCNQ1 channel currents. There was no significant difference in the incremental ratio of current amplitude in response to hyposmotic stress between the two KCNQ1-related currents, and the cells expressing the heteromeric channels swelled less than those with the homomeric channels or without the exogenous ones. The cell swelling-induced I(Ks) enhancement was not affected by a protein tyrosine kinase (PTK) inhibitor, by genistein (50 microM), or by an inhibitor of phosphotyrosine phosphatase (PTP), orthovanadate (500 microM), or a nonhydrolyzable ATP analogue, AMP-PNP (5 mM). Taken together, it is very likely that KCNQ1 might primarily participate in the I(Ks) enhancement by osmotic cell swelling. The obligatory dependence of the I(Ks) augmentation on PTK activity remained to be demonstrated, at least, in this expression system.     

Inhibition of MAP kinase activity moderates changes in expression and function of Cx32 but not claudin-1 during DNA synthesis in primary cultures of rat hepatocytes

The signal transduction pathways and activation of the MAP kinase or PI3 kinase signaling cascade regulate a variety of cellular processes, including proliferation and differentiation in hepatocytes. To elucidate the mechanisms of signal transmission required for the regulation of gap and tight junctions during DNA synthesis in rat hepatocytes, we determined changes of expression and function of gap and tight junctions of cells grown in primary culture, using inhibitors of signaling pathways for MAP kinase (PD98059) and PI3 kinase (LY294002). During the stimulation of DNA synthesis induced by epidermal growth factor (EGF), immunoreactivity and mRNAs of gap junction protein Cx32 and of tight junction protein claudin-1 markedly decreased with reduction of gap junctional intercellular communication (GJIC) and the fence function of tight junctions. In Western blots, whole-cell lysate of claudin-1 protein decreased and phosphorylated Cx32 protein in the insoluble fraction of Triton X-100 increased during the stimulation of DNA synthesis. During reinhibition of DNA synthesis, the changes of Cx32 and claudin-1 returned to control levels, as did both functions. In treatment with the inhibitors before DNA synthesis, PD98059 inhibited the changes of expression and function of Cx32, but not claudin-1, without inhibition of cell growth, whereas LY294002 completely inhibited cell growth. These findings indicate that the PI3 kinase pathway rather than the MAP kinase pathway plays an important role for EGF-induced proliferation of rat hepatocytes, and that changes of Cx32 in hepatocytes during the stimulation of DNA synthesis may be in part controlled through MAP kinase. Furthermore, Cx32, but not claudin-1, protein may be a target of activated MAP kinase in hepatocytes.     

Observation of cavitation in a mechanical heart valve in a total artificial heart

Recently, cavitation on the surface of mechanical heart valves has been studied as a cause of fractures occurring in implanted mechanical heart valves. The cause of cavitation in mechanical heart valves was investigated using the 25 mm Medtronic Hall valve and the 23 mm Omnicarbon valve. Closing of these valves in the mitral position was simulated in an electrohydraulic totally artificial heart. Tests were conducted under physiologic pressures at heart rates from 60 to 100 beats per minute with cardiac outputs from 4.8 to 7.7 L/min. The disk closing motion was measured by a laser displacement sensor. A high-speed video camera was used to observe the cavitation bubbles in the mechanical heart valves. The maximum closing velocity of the Omnicarbon valve was faster than that of the Medtronic Hall valve. In both valves, the closing velocity of the leaflet, used as the cavitation threshold, was approximately 1.3-1.5 m/s. In the case of the Medtronic Hall valve, cavitation bubbles were generated by the squeeze flow and by the effects of the venturi and the water hammer. With the Omnicarbon valve, the cavitation bubbles were generated by the squeeze flow and the water hammer. The mechanism leading to the development of cavitation bubbles depended on the valve closing velocity and the valve stop geometry. Most of the cavitation bubbles were observed around the valve stop and were generated by the squeeze flow.     

Response of epididymal duct to the temporary depletion of spermatozoa induced by testicular irradiation in mice

The mouse epididymal duct can be histologically divided into five segments (I-V), and the principal cells in segment II appear to secrete periodic acid-Schiff (PAS)-positive material into the lumen. In this study, male dd-mice received one, two, or four 800-R doses of radiation beginning at age 50 days. Mice receiving multiple doses were irradiated at 1-week intervals. After irradiation, marked depletion of spermatozoa, or aspermia, occurred in the epididymal duct for 2 to 16 weeks after a latency period of 3 to 4 weeks according to the times of irradiations. During oligospermia or aspermia, PAS-positive inclusions appeared in the principal cells in segment IV. The inclusions occupied a supranuclear position and appeared as round granules and globules measuring 2-15 micron in diameter, and increased in number, size, and staining intensity with time. They disappeared after reappearance of spermatozoa. The findings suggest that PAS-positive material may bind to spermatozoa and, if not bound, is reabsorbed by the principal cells in segment IV and deposited as intracellular inclusions, and the principal cells in segment IV are capable of digesting the accumulated PAS-positive material.