Activation of neutrophil function by recombinant human granulocyte colony-stimulating factor improves the survival of rats with peritonitis

We examined the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and cefmetazole sodium on survival, neutrophil count, and neutrophil function in rats with peritonitis produced by cecal ligation and puncture. Rats with peritonitis received either rhG-CSF (50 or 100 g/kg) with or without cefmetazole (50 mg/kg) for 3 days, cefmetazole alone, or no treatment and were evaluated as controls. The mortality rate of all treated rats was significantly lower than that of the untreated rats. The survival rate was 57.1% for the rats given both rhG-CSF and cefmetazole, but there was no significant improvement of survival as compared with cefmetazole therapy alone. Treatment with rhG-CSF at 100 |Gmg/kg caused the circulating neutrophil count to increase significantly. The phagocytic activity for latex beads and neutrophil H₂O₂ production showed a greater enhancement by phorbol myristate acetate (PMA) in the untreated rats, thus indicating that neutrophils from treated rats were more activated. These findings show that rhG-CSF can improve survival and neutrophil function in rats with peritonitis, while combined therapy with cefmetazole was also found to be beneficial.     

Use of dermal fat grafts for treating anetoderma with lipoatrophy following involution of hemangiomas

Infantile hemangioma (IH) is a benign vascular tumor that gradually involutes over several years. Rapidly involuting congenital hemangioma (RICH) is the relatively rare congenital vascular tumor that is fully grown at birth and does not undergo postnatal growth and involutes during the first year. However, after involution of both IH and RICH, some have severe sequelae, such as redundant skin or conspicuous scarring, requiring additional treatment. We present the case of a 6-year-old girl with a concave deformity due to subcutaneous atrophy, skin darkening, and altered skin texture of her left zygomatic region following involution of a hemangioma. We successfully treated this patient by transferring a dermal fat graft. This technique can be beneficial for atrophic sequelae after regression of a hemangioma and is easy to perform and cosmetically effective.     

Ultrasonic measurement of the effects of light irradiation and presence of water on the polymerization of self‐adhesive resin cement

Self‐adhesive resin cements are useful in restorations because they reduce the number of clinical steps involved in the restoration process. This study evaluated, using ultrasonic measurements, the influence of light irradiation and the presence of water on the polymerization behavior and elastic modulus of a self‐adhesive resin cement. A self‐adhesive resin cement (RelyX Unicem 2 Automix) or a resin cement (RelyX ARC) was inserted into a transparent mold on a sample stage, and the presence of water and effect of light‐irradiation were evaluated. The transit time of a sonic wave through the cement disk was divided by the specimen thickness to obtain the sonic velocity, and longitudinal and shear waves were used to determine the elastic modulus. When the resin cements were light‐irradiated, the sonic velocity rapidly increased and plateaued at 2,500–2,700 m s^?1. When the cements were not irradiated, the rates of increase in the sonic velocity were reduced. When water was applied to the sample stage, the sonic velocity was reduced. The elastic modulus values of the specimens ranged from 9.9 to 15.9 GPa after 24 h. The polymerization behavior of self‐adhesive resin cements is affected by the polymerization mode and the presence of water.     

Anatomical study of the articular branches innervated the hip and knee joint with reference to mechanism of referral pain in hip joint disease patients

Introduction : Referred pain in the anterior knee joint is the most common symptom in hip disease patients. The development of referred pain is considered to be related to dichotomizing peripheral sensory fibers. However, no gross anatomical findings identify any dichotomizing fibers innervating both the hip and knee joints. We dissected the femoral and obturator nerves in human cadavers to investigate the distribution of the articular branches in the hip and knee joints. Fourteen embalmed left lower limbs from 14 Japanese adult cadavers (five from females, nine from males, average age 73.8 ± 14.1 years) were observed macroscopically. The articular branches of the femoral and obturator nerves were dissected at the anterior margin of the groin toward the thigh region. After dissections of the articular nerves of the hip joints, the femoral and obturator nerves were exposed from proximally to distally to identify the articular nerves of the knee joints. The branching pattern of the articular branches in the hip and knee joints was recorded. In six of 14 limbs (42.9%), the femoral nerve supplied articular branches to the anteromedial aspect of both the hip and knee joints. These articular branches were derived from the same bundle of femoral nerve. These gross anatomical findings suggested that dichotomizing peripheral sensory fibers innervate the hip and knee joints and these could relate to the referred pain confirmed in the anterior knee joints of patients with hip disease. Clin. Anat. 31:705–709, 2018. © 2018 Wiley Periodicals, Inc.     

Blockade of Rho/Rho-associated coiled coil-forming kinase signaling can prevent progression of hepatocellular carcinoma in matrix metalloproteinase-dependent manner

Aim:  There is growing evidence that the Rho/Rho-associated coiled coil-forming kinase (ROCK) signaling pathway is upregulated in tumors and plays a key role in cancer invasion and metastasis. Our aim was to test the anticancer effects of Rho/ROCK inhibitor, Y-27632, including possible mechanisms in a highly-metastasizing hepatocellular carcinoma (HCC) mouse model on its secretion of matrix metalloproteinase (MMP) and tumor progression.
Methods:  Following orthotopic implantation of CBO140C12 HCC tumor fragments into the liver of mice, the mice were randomly assigned to a Y-27632-treated group or control group. After treatment for 4 weeks, specimens were obtained to evaluate tumor size, metastases, and immunohistochemical findings. In vitro , we examined the effects of Y-27632 and RhoC siRNA on MMP-2 and -9 expressions, invasiveness, and apoptosis in cultured tumor cells.
Results:  Both RhoA and RhoC were upregulated in HCC-bearing livers, and Y-27632 significantly inhibited not only tumor growth and intrahepatic metastasis ( P  < 0.05), but also tumoral MMP-9 expression. Moreover, Y-27632 treatment resulted in large necrotic areas in tumors. In vitro , Y-27632 and RhoC siRNA reduced MMP-2 and -9 expressions, as well as the chemotactic migration of tumor cells dose-dependently, and increased apoptosis eight times.
Conclusion:  Y-27632 suppresses progression and limits the intrahepatic metastasis of established HCC. This could be linked to the decreased MMP expression and induction of apoptosis in tumor cells. Rho signaling may prove to be a productive target in anticancer therapy.     

Targeted mutations of the juxtamembrane tyrosines in the Kit receptor tyrosine kinase selectively affect multiple cell lineages

Loss-of-function mutations in the murine dominant white spotting/c-kit locus affect a diverse array of biological processes and cell lineages and cause a range of phenotypes, including severe anemia, defective pigmentation, sterility, mast cell deficits, a lack of interstitial cells of Cajal, spatial learning memory deficits, and defects in peripheral nerve regeneration. Here we show that tyrosine residues 567 and 569 in the juxtamembrane (Jx) domain of the murine Kit receptor tyrosine kinase are crucial for the function of Kit in melanogenesis and mast cell development, but are dispensable for the normal development of erythroid, interstitial cells of Cajal and germ cells. Furthermore, adult mice lacking both tyrosines exhibit splenomegaly, dysregulation of B-cell and megakaryocyte development, and enlarged stomachs. Analysis of signal transduction events induced by the mutant receptors after ligand stimulation indicates that Jx tyrosine mutations diminish receptor autophosphorylation and selectively attenuate activation of extracellular signal-regulated kinase/mitogen-activated protein kinases. Together, these observations demonstrate that the Jx domain of Kit plays a cell-type specific regulatory role in vivo and illustrate how engineered mutations in Kit can be used to understand the complex biological and molecular events that result from activating a receptor tyrosine kinase.