Spatial orientation of caloric nystagmus in semicircular canal-plugged monkeys

We studied caloric nystagmus before and after plugging all six semicircular canals to determine whether velocity storage contributed to the spatial orientation of caloric nystagmus. Monkeys were stimulated unilaterally with cold ( approximately 20 degrees C) water while upright, supine, prone, right-side down, and left-side down. The decline in the slow phase velocity vector was determined over the last 37% of the nystagmus, at a time when the response was largely due to activation of velocity storage. Before plugging, yaw components varied with the convective flow of endolymph in the lateral canals in all head orientations. Plugging blocked endolymph flow, eliminating convection currents. Despite this, caloric nystagmus was readily elicited, but the horizontal component was always toward the stimulated (ipsilateral) side, regardless of head position relative to gravity. When upright, the slow phase velocity vector was close to the yaw and spatial vertical axes. Roll components became stronger in supine and prone positions, and vertical components were enhanced in side down positions. In each case, this brought the velocity vectors toward alignment with the spatial vertical. Consistent with principles governing the orientation of velocity storage, when the yaw component of the velocity vector was positive, the cross-coupled pitch or roll components brought the vector upward in space. Conversely, when yaw eye velocity vector was downward in the head coordinate frame, i.e., negative, pitch and roll were downward in space. The data could not be modeled simply by a reduction in activity in the ipsilateral vestibular nerve, which would direct the velocity vector along the roll direction. Since there is no cross coupling from roll to yaw, velocity storage alone could not rotate the vector to fit the data. We postulated, therefore, that cooling had caused contraction of the endolymph in the plugged canals. This contraction would deflect the cupula toward the plug, simulating ampullofugal flow of endolymph. Inhibition and excitation induced by such cupula deflection fit the data well in the upright position but not in lateral or prone/supine conditions. Data fits in these positions required the addition of a spatially orientated, velocity storage component. We conclude, therefore, that three factors produce cold caloric nystagmus after canal plugging: inhibition of activity in ampullary nerves, contraction of endolymph in the stimulated canals, and orientation of eye velocity to gravity through velocity storage. Although the response to convection currents dominates the normal response to caloric stimulation, velocity storage probably also contributes to the orientation of eye velocity.     

Diversified expression patterns of autotaxin,a gene for phospholipid‐generating enzyme during mouse and chicken development

Autotaxin (ATX), or nucleotide pyrophosphatase‐phosphodiesterase 2, is a secreted lysophospholipase D that generates bioactive phospholipids that act on G protein–coupled receptors. Here we show the expression patterns of the ATX gene in mouse and chicken embryos. ATX has a dynamic spatial and temporal expression pattern in both species and the expression domains during neural development are quite distinct from each other. Murine ATX (mATX) is expressed immediately rostral to the midbrain‐hindbrain boundary, whereas chicken ATX (cATX) is expressed in the diencephalon and later in the parencephalon‐synencephalon boundary. In the neural tube, cATX is expressed in the alar plate in contrast to mATX in the floor plate. ATX is also expressed in the hindbrain and various organ primordia such as face anlagen and skin appendages of the mouse and chicken. These results suggest conserved and non‐conserved roles for ATX during neural development and organogenesis in these species. Developmental Dynamics 236:1134–1143, 2007. © 2007 Wiley‐Liss, Inc.     

Neuronal death in the developing sexually dimorphic periventricular nucleus of the preoptic area in the female rat: effect of neonatal androgen treatment

Neonatal treatment of female rats with androgen decreases the nuclear volume of the anteroventral periventricular nucleus of the preoptic area (AVPv-POA). In order to examine the effect of androgen on the neural substrates in the developing AVPv-POA which show a sexual dimorphism in nuclear volume, the cell death pattern in the AVPv-POA was compared between normal females and androgenized females. Wistar female rats were treated with 50 micrograms of testosterone propionate (TP) for 5 days from the day of birth. Degenerating cells (pyenotic cells) and normal cells were counted in every third section from days 1 to 13 of life. The rate of pycnotic cells to 1000 cells in TP-treated females sacrificed at days 7 and 10 was significantly higher than that in normal females. These results may suggest that neonatal androgen regulates neuronal death in the AVPv-POA, decreasing the number of neurons in the nucleus.     

Association of Lyn tyrosine kinase to the GM-CSF and IL-3 receptor common betac subunit and role of Src tyrosine kinases in DNA synthesis and anti-apoptosis

BACKGROUND: After GM-CSF or IL-3 stimulation, the activation of JAK2 tyrosine kinase and members of the Src family of tyrosine kinases takes place, followed by phosphorylation of betac tyrosine residues and the recruitment of SH2 containing molecules to the receptor complex. The exact role of Src kinases such as Lyn in this and other downstream signal transduction events remains unclear. RESULTS: We investigated the association of Lyn kinase with betac using synthetic peptides derived from the eight betac tyrosine residues and the Box 1 motif. We found that Lyn kinase GST fusion proteins bind to peptides corresponding to the membrane proximal region of betac and to peptides containing specific betac derived phosphorylated tyrosine residues. We also determined that betac tyrosine residues Y1,2 as well as Y7 and Y8 can act as substrates of Lyn. We further analysed the role of the Src kinases in DNA synthesis and anti-apoptosis downstream of GM-CSF by using the Src kinase inhibitor PP1 in murine BA/F3 cells stably expressing a series of mutant betac receptors. CONCLUSIONS: Lyn binds to betac derived peptides through multiple interactions, and may play an important role in betac phosphorylation. Src family kinases also play an essential role in GM-CSF mediated DNA synthesis, as well as an important role in anti-apoptosis in response to GM-CSF.     

Mevalonic acidemia: First case of Japan

Summary Mevalonic acidemia is a rare metabolic disorder due to mevalonate kinase deficiency which affects the biosynthesis of cholesterol and nonsterol isoprenes. We report the first case of Japan. The clinical course is characterized by intrauterine growth retardation, postnatal growth failure, intractable diarrhea, liver dysfunctions and death at three months of age. Dysmorphic features including triangular face, protrusion of forehead, hypertelorism, low set ears and micrognathism were noted. High mevalonic acid level was found by GC/MS.     

Chromosome 1q terminal deletion resulting fromde novo translocation with an acrocentric chromosome

Summary Distal deletion of chromosome 1q has been reported in nearly 30 patients, all being associated with a deletion ranging from the 1q42 or q43 band to 1qter region. Here, we describe a girl with 1q terminal deletion resulting from an unbalancedde novo translocation t(1;D or G)(q44; p11), as revealed by the presence of a satellited feature and an NOR-stained region at the tip of 1q. We suggest that most of the phenotypic abnormalities seen in patients with 1q distal deletion are attributable to the monosomy for band 1q44.     

Ectopic expression of activated Stat6 induces the expression of Th2-specific cytokines and transcription factors in developing Th1 cells

Stat6 is critical for IL-4-mediated Th2 cell development, but its molecular mechanism remains unclear. Here we constructed Stat6:ER, a Stat6-estrogen receptor fusion protein that can be activated by 4-hydroxy-tamoxifen, independently of IL-4 and endogenous Stat6. Retrovirus-mediated introduction of Stat6:ER into developing Th1 cells induced Th2-specific cytokines and suppressed IFNgamma production in a 4-HT-dependent manner and in the absence of IL-4. It also induced GATA-3 and c-maf expression and downregulated IL-12Rbeta2 chain expression. Its decreased ability to induce the Th2 phenotype with progressing Th1 cell commitment correlated with a decreased induction of GATA-3 and c-maf. This study indicates that Stat6 functions upstream of GATA-3 and c-Maf to induce Th2 development.     

Heterotopic gastric mucosa of the small intestine in laboratory beagle dogs

Out of the 365 young laboratory beagle dogs which were used in 17 toxicity bioassays, 15 cases (4.1%) were diagnosed as having congenital heterotopic gastric mucosa of the small intestine. Its incidence in the male dogs (12 cases out of 187) was higher than in the female dogs (3 cases out of 178). Grossly, the lesions were seen as an ulcerous focus of the small intestine, 25 cm to 88 cm proximal to the ileocecal valve. All of the lesions were quite similar histologically and electron microscopically to the normal gastric mucosa, which are composed of the surface mucous cells, chief cells, parietal cells, mucous neck cells and basal granulated cells of the stomach. And consequently, they were considered to be that of a congenital heterotopic tissue in the small intestine. The only morphological characteristic of these lesions different from the regular gastric mucosa was an association with the tubular structure seen in the basal region of these mucosal layers. These cells were considered to be of mucous-secreting cell origin because of secreting type III mucous evident from paradoxical concanavalin A or periodic acid Schiff stains. They seemed to be protecting the surrounding intestinal mucosa from gastric acid.     

Activation of lymphokine genes during stimulation of cloned T cells

To study the regulation of lymphokine production by T lymphocytes, we have characterized the activation of lymphokine genes in T cells by measuring the levels of lymphokine mRNA in cloned murine T lymphocytes after stimulation. Lymphokine mRNA was not detected in cells taken after seven days of maintenance culture. Following stimulation of T helper lymphocytes L2 and AD9.1 with concanavalin A, lymphokine mRNA appeared, reached peak levels and disappeared over a 43-h time period. A single stimulation event resulted in the induction of mRNA for interleukin 2 (IL 2), IL 3 and interferon gamma. Maximal mRNA levels were generally found at 6 h in the T helper lymphocytes, but could occur as late as 18 h. The lymphokine genes were expressed coordinately; however, in these cloned cells, IL 2 mRNA levels appeared to be lower than the other two mRNAs. Lymphokine titers in the supernatant fluids paralleled the appearance of mRNA but IL 2 titers began to fall after 12 h probably because of utilization of this lymphokine by the activated cells. In the cytolytic T lymphocyte, L3, qualitatively similar kinetics were found after stimulation by lectin or a clonotypic antibody with peak mRNA levels occurring later (18 h) with the antibody. These studies indicate a single stimulating event activates the lymphokine genes of T cells in a coordinate manner; the appearance of the lymphokines in supernatant fluids represents de novo synthesis of these proteins but the levels of lymphokines measured in supernatant fluids reflects both production and utilization rates, and exposure to IL 2 at the time of stimulation is not essential for the production of other lymphokines.     

Hypothalamic laterality in regulating gonadotropic function: unilateral hypothalamic lesion and ovarian compensatory hypertrophy

Regardless of the side of hemiovariectomy, unilateral lesion placed in the right-side medial anterior hypothalamus suppressed ovarian compensatory hypertrophy, but the lesion made in the left side failed to suppress it. This suggests the presence of a hypothalamic laterality in regulating gonadotropin secretion.