Bleeding esophageal varices caused by Graves' hypervascular cervical goiter

A 65-year-old woman presented with an episode of hematemesis and a recurrent cervical goiter due to Graves' disease. The angiogram revealed bleeding esophageal varices which had developed through a drainage vein of the vascular goiter. Total thyroidectomy resulted in eradication of the esophageal varices.     

Fine structure of soft and hard tissues involved in eye migration in metamorphosing Japanese flounder (Paralichthys olivaceus)

The body of a Japanese flounder (Paralichthys olivaceus) changes from a symmetrical to an asymmetrical form during metamorphosis. To obtain detailed information on the mechanisms of the migration of the right eye to the left side, soft and hard tissues in the head of larval flounders were examined using transmission electron microscopy (TEM). Retrorbital vesicles (Rvs) are pairs of sac-like structures under the eyes. It has been suggested that the asymmetrical development of Rvs, with the right (blind) one being bigger than the left, is the driving force behind eye migration. The present study revealed that the ultrastructure of the Rv sheath is quite similar to that of a lymphatic capillary. Thus, it is possible that the Rv is a part of the lymph system, and is probably related to the secondary vascular system in teleosts. If we assume that the Rv sheath has a high permeability to liquid, similar to lymphatic capillaries, it is not plausible that the active expansion of the Rv pushes the eyeball. On the other hand, the pseudomesial bar (Pb) is a bone that is unique to flounders and is present only on the right (blind) side. At the beginning of eye migration, an aggregation of fibroblast-like cells is observed in the dermis under the right eye, where the Pb will subsequently be formed. These cells have a well-developed rough endoplasmic reticulum (rER) and mitochondria, and are probably responsible for formation of the thick layers of collagen fibrils around them. Since it is unlikely that the active expansion of the Rv causes eye migration, the role played by the Pb and its rudiment becomes more significant in right eye migration in the Japanese flounder becomes more significant.     

Glutathione redox regulates lipopolysaccharide-induced IL-12 production through p38 mitogen-activated protein kinase activation in human monocytes: role of glutathione redox in IFN-gamma priming of IL-12 production

We examined whether changes in intracellular reduced (GSH) or oxidized (GSSG) glutathione of human monocytes regulate lipopolysaccharide (LPS)-induced IL-12 production and defined the molecular mechanism that underlies glutathione redox regulation. Monocytes exposed to glutathione reduced form ethyl ester (GSH-OEt) or maleic acid diethyl ester (DEM) increased or decreased the intracellular GSH/GSSG ratio, respectively. LPS-induced IL-12 production and p38 mitogen-activated protein (MAP) kinase activation were enhanced by GSH-OEt but suppressed by DEM. Selective p38 inhibitors showed that p38 promoted GSH-OEt-enhanced IL-12 production. Furthermore, IFN-gamma priming increased the GSH/GSSG ratio and enhanced IL-12 production through p38, and DEM negated the priming effect of IFN-gamma on p38 activation and IL-12 production as well as on the GSH/GSSG ratio. These findings reveal that glutathione redox regulates LPS-induced IL-12 production from monocytes through p38 MAP kinase activation and that the priming effect of IFN-gamma on IL-12 production is partly a result of the glutathione redox balance.     

Influence of sperm immobilization on onset of Ca(2+) oscillations after ICSI

Sperm immobilization prior to intracytoplasmic sperm injection (ICSI) is thought to be necessary for efficient fertilization. A variety of methods of sperm immobilization (pipetting, squeezing and piezo application) are currently employed in ICSI. The effect of differences in immobilization method on the timing of initial Ca(2+) oscillations of oocytes in ICSI was investigated. Motile spermatozoa were immobilized in eosin Y solution using pipetting, squeezing and piezo application. Complete staining of the sperm head was achieved after 220.7, 42.2 and 5.0 s respectively. Oscillations after ICSI were measured fluorometrically for each method. The onset of Ca(2+) oscillations was observed at 4.8 to 80.4 min after ICSI. Ca(2+) oscillations developed earlier with the piezo method (14.4 +/- 6.4 min) than other methods (pipetting, 43.1 +/- 20.2 min, P < 0.01; squeezing, 18.4 +/- 3.8 min, P = NS). The piezo method produced the earliest staining of the sperm head and may have caused the most damage to the sperm membrane. A more rapid onset of Ca(2+) oscillations was also observed with the piezo method. The method of sperm immobilization may be important for the rapid release of sperm factors that initiate oocyte activation. This study also showed that Ca(2+) oscillations develop earlier in human oocytes treated by ICSI than indicated in previous reports.     

B Lymphocyte signaling established by the CD19/CD22 loop regulates autoimmunity in the tight-skin mouse

Systemic sclerosis (SSc) is characterized by fibrosis and autoimmmunity. Peripheral blood B cells from SSc patients specifically overexpress CD19, a critical cell-surface signal transduction molecule in B cells. CD19 deficiency in B cells also attenuates skin fibrosis in the tight-skin (TSK/+) mouse, a genetic model for SSc. Herein we analyzed two transgenic mouse lines that overexpress CD19. Remarkably, 20% increase of CD19 expression in mice spontaneously induced SSc-specific anti-DNA topoisomerase I (topo I) antibody (Ab) production, which was further augmented by 200% overexpression. In TSK/+ mice overexpressing CD19, skin thickness did not increase, although anti-topo I Ab levels were significantly augmented, indicating that abnormal CD19 signaling influences autoimmunity in TSK/+ mice and also that anti-topo I Ab does not have a pathogenic role. The molecular mechanisms for abnormal CD19 signaling were further assessed. B-cell antigen receptor crosslinking induced exaggerated calcium responses and augmented activation of extracellular signal-regulated kinase in TSK/+ B cells. CD22 function was specifically impaired in TSK/+ B cells. Consistently, CD19, a major target of CD22-negative regulation, was hyperphosphorylated in TSK/+ B cells. These findings indicate that reduced inhibitory signal provided by CD22 results in abnormal activation of signaling pathways including CD19 in TSK/+ mice and also suggest that this disrupted B cell signaling contribute to specific autoantibody production.     

A new method for assaying adhesion of cancer cells to the greater omentum and its application for evaluating anti-adhesion activities of chemically synthesized oligosaccharides

A new ex vivo method for assaying adhesion of cancer cells to the greater omentum has been developed using mouse greater omentum and [³H]labelled human gastric and mouse colorectal cancer cells. Since the adhesion rates were found to increase up to 18 h and labelled cells seemed to be stable during the period, the present method could be useful for investigating adhesion of cancer cells to the greater omentum, which must occur at the first step of the peritoneal dissemination. The adhesion of cancer cells to the greater omentum was inhibited by a series of chemically synthesized oligosaccharides and Galβ1,3[3OMeGalβ1,4GlcNAcβ1,6]αBn was found to be the best inhibitor. The anti-tumor effect of this novel tetrasaccharide in vivo was shown in preliminary experiments using Balb/c mice and colon26 cells.     

Consistency behind trial-to-trial variation in intrinsic optical responses to single-whisker movement in the rat D1-barrel cortex

We examined consistent characteristics behind the trial-to-trial variati on in intrinsic optical imaging of single barrel cortical responses to D 1-whisker movement in 2-5-week postnatal (2-5 W) and adul t (>9-weeks) Wistar rats, and we identified the effective are a of the neural response. The extent/size, configuration and orientation of the intrinsic optical response area varied from trial-to-trial with the same whisker stimulation. We argue that the trial-to-trial variation was due to cortical blood circulation related to the barrel neural activity. Subsequently, interpolating a family of the traces of the optical response area imaged with repeated stimulation for each animal, we extracted a centered circular area from the trial-to-trial response for each animal. Although the trial-to-trial variation decreased gradually with age, the spatial extent of the interpolated response area was consistently about 660 microm in diameter, in agreement with that measured morphologically and/or histochemically. A possible interpretation is that the optically defined area appears to image the actual effective single-barrel response area, as a first approximation. Furthermore, the constancy of the extracted area independent of age suggests that the barrel cortex is, in fact, virtually mature by 2 weeks of age. The extracted area was also nearly independent of the frequency (>/=5 Hz) of whisker movement.