Alterations in sympathetic nervous system activity do not regulate adipsin gene expression in mice.

Adipsin gene expression is severely diminished in certain forms of genetic and acquired rodent obesity. Common to many of these models of obesity is decreased sympathetic nervous system (SNS) activity. In addition, treatment of MSG obese mice with the sympathomimetic drug mixture ephedrine and caffeine restores adipsin deficiency to normal, while reversing obesity. Based on these observations, we hypothesized that adipsin gene expression might be regulated through changes in SNS activity with deficient adipsin gene expression in obesity being the result of impaired SNS activity. In the present study we used three models to assess the role of the SNS in regulating adipsin gene expression. First we exposed mice to the cold (4 degrees C), a potent activator of SNS activity. Second, we chemically sympathectomized mice with 60H-dopamine. Third, we treated mice with BRL 26830A, an atypical beta adrenoreceptor agonist. In contrast to our initial hypothesis, these studies demonstrate that alterations of SNS activity do not affect adipsin gene expression in normal mice. Neither increased SNS activity secondary to cold exposure nor decreased SNS activity resulting from sympathectomy alter serum adipsin concentration or adipsin mRNA levels in white (WAT) and brown adipose tissue (BAT). Surprisingly, treatment of lean mice with BRL 26830A decreases both adipsin serum concentrations and adipsin mRNA levels, suggesting a potential role for atypical beta adrenoreceptors in pathways that suppress adipsin expression in vivo. The significance of this observation with respect to adipocyte physiology is unclear at present. Future studies will be aimed at defining the molecular mechanisms by which BRL 26830A suppresses adipsin gene expression and the physiological significance of this effect.     

Essential role of Src-family protein tyrosine kinases in NF-kappaB activation during B cell development

The nature of signals that govern the development of immunoglobulin heavy chain-dependent B cells is largely unknown. Using mice deficient for the B cell-expressed Src-family protein tyrosine kinases (SFKs) Blk, Fyn and Lyn, we show an essential role of these kinases in pre-B cell receptor (pre-BCR)- mediated NF-kappaB activation and B cell development. This signaling defect is SFK specific, as a deficiency in Syk, which controls pre-B cell development, does not affect NF-kappaB induction. Impaired NF-kappaB induction was overcome by the activation of protein kinase C (PKC)-lambda, thus suggesting the involvement of PKC-lambda in pre-BCR-mediated SFK-dependent activation of NF-kappaB. Our data show the existence of a functionally distinct SFK signaling module responsible for pre-BCR-mediated NF-kappaB activation and B cell development.     

The Src kinase Lyn is a negative regulator of mast cell proliferation

Previous investigators have reported that deletion of the protein tyrosine kinase Lyn alters mast cell (MC) signaling responses but does not affect or reduces the cytokine-mediated proliferation of mouse bone marrow-derived MC (BMMC) precursors and of mature MC. We observed that Lyn-deficient mice have more peritoneal MC than wild-type (WT) mice. Studies to explore this unexpected result showed that Lyn(-/-) BM cells expand faster than WT cells in response to interleukin (IL)-3 and stem-cell factor over the 4-5 weeks required to produce a >95% pure population of granular, receptor with high affinity for immunoglobulin E-positive BMMC. Furthermore, differentiated Lyn(-/-) BMMC continue to proliferate more rapidly than WT BMMC and undergo less apoptosis in response to cytokine withdrawal. Additionally, Lyn(-/-) BMMC support greater IL-3-mediated phosphorylation of the prosurvival kinase, Akt, and the proliferative kinase, extracellular-regulated kinase 1/2. These results identify Lyn as a negative regulator of murine MC survival and proliferation.     

Renal Ultrasound Changes After Pyeloplasty in Children With Ureteropelvic Junction Obstruction: Long-term Outcome in 47 Renal Units

Purpose

We evaluated the use of renal ultrasound for monitoring pyelocaliectasis after pyeloplasty in children.

Materials and Methods

Changes in pyelocaliceal dilatation following pyeloplasty were assessed by serial ultrasound. Of 104 children 0 to 12 years old who underwent pyeloplasty between 1982 and 1992, 44 (47 renal units) were monitored with serial ultrasound for at least 2 years (range 2 to 9, mean 3.8). Patient ages at pyeloplasty were 0 to 3 months (17), 4 to 12 months (8), 1 to 6 years (13) and 7 to 12 years (6). Preoperative and postoperative ultrasound was reviewed by a single pediatric radiologist blinded to the date of surgery. The degree of pyelocaliectasis was graded as 0 to 4 according to the classification of the Society for Fetal Urology.

Results

Preoperative ultrasound revealed grade 4 pyelocaliectasis in 26 kidneys (55 percent) and grade 3 disease in 21 (45 percent). Grade was the same or worse 1 month after pyeloplasty in the majority of kidneys (92 percent) studied at this interval. Of the 47 renal units assessed 43 (91 percent) showed improvement in pyelocaliectasis during postoperative followup. Only 38 percent of the kidneys improved during the first 6 months of followup, while 81 percent were improved 2 years postoperatively. Improvement to grade 0 or 1 dilatation occurred in only 9 kidneys (19 percent). The rate of resolution of pyelocaliectasis was not related to preoperative grade or patient age at pyeloplasty.

Conclusions

Improvement on renal ultrasound after pyeloplasty appears to be gradual. Less than half of the patients had improvement in the initial 6 months after pyeloplasty and pyelocaliectasis rarely resolved completely. While renal ultrasound can provide an accurate and cost-effective means of monitoring children on a long-term basis after pyeloplasty, sonographic evaluation in the early postoperative period commonly shows increased or unchanged pyelocaliectasis.