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.     

The properties of the Kir6.1–6.2 tandem channel co-expressed with SUR2A

Functional ATP-sensitive K (KATP) channels have an octameric subunit structure with four pore-forming subunits (Kir6.x) and four sulfonylurea receptors (SURx). In the present study, the properties of the heteromeric KATP channel whose pore subunits are composed of Kir6.1 and Kir6.2 were examined using a heterologous expression system. In COS7 cells co-transfected with Kir6.1, Kir6.2 and SUR2A at a ratio of 1:1:2, KATP channels showed various unitary conductances between those of Kir6.1/SUR2A (33.6+/-4.2 pS) and Kir6.2/ SUR2A (67.1+/-1.6 pS). Kir6.1-6.2 tandem protein, constructed by fusing the C-terminus of Kir6.1 to the N-terminus of Kir6.2 with a ten glutamine linker sequence, also formed a channel with an intermediate conductance (58.9+/-1.5 pS). Kir6.2 and Kir6.1-6.2 showed similar sensitivity to ATP4-: half-maximal inhibition (IC50) was obtained at 14.1+/-12.8 microM and 17.6+/-9.6 microM, respectively. In the presence of Mg2+, Kir6. 1-6.2 was significantly less sensitive than Kir6.2 to MgATP (IC50=95.5+/-49.6 microM versus 18.9+/-5.0 microM). These results suggest that Kir6.1 and Kir6.2 are endowed with the potential to form a heteromeric KATP channel, which has a low sensitivity to MgATP.     

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.     

Stereological analysis of Reinke's crystals in human Leydig cells

Summary Reinke's crystals in human Leydig cells were analyzed stereologically to assess their functional role. Testicular tissues were taken from seven older men (57–82 years old) with prostatic carcinoma and also from seven younger men (26–38 y.o.) complaining of male infertility. Sections 0.5 m thick, stained with toluidine blue or Heidenhein's iron-hematoxylin were examined by a point-counting method and with a Particle Measurement Computor System (MC). When the patients were grouped by age, the mean crystal volume, the number of crystals per cell, the volume of crystals per cell and the volume ratio of crystals to cell were significantly larger in the older age group than in the younger age group. In particular, the latter three variables correlated well with the age of subjects, with correlation coefficients of r=0.66–0.85. On the other hand, none of these variables had any correlation with the concentration of plasma testosterone. These results indicate that Reinke's crystals can be considered as degenerative products in cell life but not as facultative constituents for testosterone production.Supported in part by a grant from Medical Foundation of Ehime, Japan     

Immunolocalization of aromatase in human minor salivary glands of the lower lip with primary Sjogren's syndrome

The enzyme aromatase Is Involved In the conversion of androgens to estrogens and in the modulation of various androgenlc and estrogenlc actions. Abnormalities of estrogen metabolism have been postulated to play roles in the development and/or pathophyslology of Sjdgren's syndrome. In the present study, aromatase was immunolocal-ized In 75 cases of Inflammatory disorders of human minor salivary glands of the lower lip. These included cases of primary Sjögren's syndrome (19 cases), of chronic slaladenitis (34 cases) and of mucous extravasation cysts (22 cases), in order to clarify the possible involvement of in situ estrogen production in primary Sjögren's syndrome. Aromatase Immunoreactlvlty was detected In myoepithelial cells of acini and in interstitial cells adjacent to acini and ducts In 13/19 (68%) cases of primary Sjögren's syndrome. In contrast, aromatase expression was detected In only six of 34 (18%) cases of chronic sialadenttis and in seven of 22 (32%) cases of mucous extravasation cyst. These results suggest that Increased aromatase expression in minor salivary glands with primary Sjogren's syndrome in premenopausal women may be involved in the biological features of primary Sjogren's syndrome through the production of estrogens in situ and possibly through the aggravation of the inflammatory reaction.     

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.     

Role of BLNK in oxidative stress signaling in B cells

BLNK (B cell linker protein) represents a central linker protein that bridges the B cell receptor-associated kinases with a multitude of signaling pathways. In this study, we have investigated the role of BLNK in oxidative stress signaling in B cells. H2O2 treatment of B cells induced a rapid tyrosine phosphorylation of BLNK in a H2O2 dose-dependent manner, which was inhibited in Syk-deficient DT40 cells. Calcium mobilization in BLNK-deficient as well as Syk-deficient and phospholipase C (PLC)-gamma2-deficient cells after H2O2 treatment was completely abolished. These were derived from decreased inositol 1,4,5-trisphosphate generation through PLC-gamma2 in BLNK-deficient cells. Moreover, viability of BLNK-deficient as well as PLC-gamma2-deficient cells after exposure to low doses of H2O2 was dramatically enhanced compared with that of the wild-type cells. Furthermore, c-Jun N-terminal kinase activation following high doses of H2O2 stimulation, but not low doses of H2O2 stimulation, was abrogated in BLNK-deficient as well as Syk-deficient cells. These findings have led to the suggestion that BLNK is required for coupling Syk to PLC-gamma2, thereby accelerating cell apoptosis in B cells exposed to low doses of H2O2.     

Turtle-chicken chimera: an experimental approach to understanding evolutionary innovation in the turtle.

Turtles have a body plan unique among vertebrates in that their ribs have shifted topographically to a superficial layer of the body and the trunk muscles are greatly reduced. Identifying the developmental factors that cause this pattern would further our understanding of the evolutionary origin of the turtles. As the first step in addressing this question, we replaced newly developed epithelial somites of the chicken at the thoracic level with those of the Chinese soft-shelled turtle Pelodiscus sinensis (P. sinensis somites into a chicken host) and observed the developmental patterning of the grafted somites in the chimera. The P. sinensis somites differentiated normally in the chicken embryonic environment into sclerotomes and dermomyotomes, and the myotomes differentiated further into the epaxial and hypaxial muscles with histological morphology similar to that of normal P. sinensis embryos and not to that of the chicken. Epaxial dermis also arose from the graft. Skeletal components, however, did not differentiate from the P. sinensis sclerotome, except for small fragments of cartilage associated with the host centrum and neural arches. We conclude that chicken and P. sinensis share the developmental programs necessary for the early differentiation of somites and that turtle-specific traits in muscle patterning arise mainly through a cell-autonomous developmental process in the somites per se. However, the mechanism for turtle-specific cartilage patterning, including that of the ribs, is not supported by the chicken embryonic environment.     

Unique three-way translocation, t(3;14;18)(q27;q32;q21), in follicular lymphoma

A 43-year-old woman was diagnosed as having stage IV follicular lymphoma. Phenotypically, the lymphoma cells were CD5(-), CD10(+), CD19(+), CD20(+), CD23(-), HLA-DR(+), and IgM-lambda(+). Conventional chromosomal analysis showed a three-way t(3;14;18)(q27;q32;q21) in the lymphoma cells, which was confirmed by spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). Immunohistochemistry revealed that both BCL2 and BCL6 proteins were expressed in the lymphoma cells, whereas only the BCL6 gene, and not the BCL2 gene, was rearranged by Southern blotting. The patient received combination chemotherapy and has been well for 3 years. This is the first reported case showing a three-way translocation involving 2 major lymphoma-specific abnormalities, 3q27 and t(14;18)(q32;q21).