Auricular reconstruction is often required for an auricular defect following tumor excision or trauma. It is
important for the reconstructed auricle to maintain a complicated three-dimensional structure and to have structural
strength against scar contracture. Many reconstruction methods for an auricular defect have ever been reported in
the literature. Reconstruction methods using only soft tissues were common in early reports, but these methods cause
postoperative deformity due to scar contracture. Therefore, reconstruction methods with a cartilage graft or using
a chondrocutaneous flap are now preferred. Reconstruction using local flaps has an advantage over reconstruction
using skin grafts because good color and texture match of the reconstructed auricle can be obtained. With elucidation
of the hemodynamics of the auricle, various local flaps around the auricle have been developed, and the stability of
blood supply of the flaps has improved. In this report, we classify the reconstruction methods and discuss the utility
of each method, and we present our strategy for partial reconstruction of the auricle.
Aim: The plasma Aβ40/42 ratio is a possible biomarker for the onset of Alzheimer's disease (AD). We
here measured plasma Aβ40 and Aß42 levels in patients with diabetes mellitus (DM) and dementia in order to clarify the relationship between DM and AD. Methods: Fifty-three patients, including 33 patients with DM and 25 patients with dementia, were assessed using the Mini-mental state examination (MMSE) and brain MRI, plasma Aβ40 and Aβ42, blood sugar levels, and HbA1c % were measured, and the genotype of apolipoprotein E was determined. Plasma Aβ levels and blood sugar levels were measured in 16 out of 53 patients, following fasting and 2 hours after breakfast. Results: Plasma Aβ40 levels and the Aβ40/42 ratio were increased in the DM with dementia group (p<0.01, p<0.001), while HbA1c % correlated with the Aβ40/42 ratio in the non-dementia group. MMSE scores were also associated with the plasma Aβ40/42 ratio and Aβ40 levels in the non-dementia group, independent of the presence of ApoEε4. We did not observed significant direct responses of plasma Aβ protains to an increase in blood sugar levels. Conclusion: These results suggest that plasma Aβ metabolism are closely related chronic hyperglycemia before the onset of dementia.
The Raf-kinase inhibitor protein (RKIP) physically binds to Raf and MEK, and inhibits the Raf/MEK/ERK signaling pathway. Transforming growth factor (TGF)-β1 is a multifunctional cytokine that has a proliferative effect on fibroblasts. A considerable effort has been applied to studies of cell growth inhibition by TGF-β1, whereas far less attention has been given to the elucidation of the mechanism of TGF-β1-induced growth stimulation. In this study, we revealed that TGF-β1 significantly enhanced the proliferation of normal human dermal fibroblasts (NHDFs). In addition, we showed that TGF-β1 inhibited the expression of RKIP mRNA and protein. Moreover, a transfection experiment demonstrated that overexpression of RKIP significantly inhibited NHDF cell growth. These data point to a relationship between enhanced NHDF cell growth and reduction of RKIP expression by TGF-β1, suggesting that TGF-β1 may induce fibroblast proliferation partly through the inhibition of RKIP. Furthermore, we revealed that EGF and PDGF-BB, known activators of the Raf/MEK/ERK signal transduction pathway, failed to modulate RKIP expression. Finally, TGF-β1 induced a transient phosphorylation of ERK1/2. Although detailed mechanisms of NHDF proliferation via RKIP are yet unknown, it will be important to investigate the molecular status of RKIP in certain proliferative diseases, such as keloids, in which TGF-β1 has been reported to play a pathogenic role by inducing hyperproliferation of dermal fibroblasts.
Dysregulation of iron homeostasis in brain causes various neurodegenerative disorders. In fact, high
concentration of iron is present in brains of patients with Alzheimer's disease. It was previously reported that
CXCL8 protects human neurons from amyloid-β-induced neurotoxicity and that astrocytes have the potential to
play important roles in Alzheimer's disease. In the present study, we examined the effect of desferrioxamine, an
iron chelator, on the expression of CXCL8 in U373MG human astrocytoma cells used as a model of astrocytes.
Treatment of the cells with desferrioxamine induced the expression of CXCL8. Pretreatment of the cells with
FeSO₄ counteracted the positive effect of desferrioxamine on CXCL8 production, suggesting that the effect of
desferrioxamine was due to iron chelation. RNA interference experiments showed that HIF-1α was not involved in
desferrioxamine-induced CXCL8 expression. We conclude that desferrioxamine induces CXCL8 in astrocytes and the
chelation of iron may be a new therapeutic strategy for Alzheimer's disease.
Tumor microenvironment is related to growth, survival, invasion, and metastasis of tumor cells. Several
studies have proved that stromal fibroblasts play an important role in the tumor microenvironment to convert
cancer-associated fibroblast (CAFs). Clock genes are known to regulate circadian rhythms, angiogenesis, and
immunoreaction. In addition, clock genes play an important role in cancer development. However, little has been
shown about how these clock genes function in the tumor microenvironment. In the present study, we investigated to
evaluate the effect of co-culture fibroblasts with oral cancer cells on the expression of clock genes. Following the co-culture of human primary fibroblasts with human gingival carcinoma Ca9-22 cells, the expression levels of clock genes were analyzed by real-time quantitative PCR. We found that the rhythmic expression of clock genes were altered, enhanced, or disappeared by the co-culture. Such effect was observed not only in fibroblasts in the presence of Ca9-22 cells but also in Ca9-22 cells in the presence of fibroblasts. Our results suggested that clock genes might affect an important role in the tumor microenvironment.
Background & Aims: Liver fibrosis progresses to cirrhosis as the consequence of chronic liver injury.
4-methylumbelliferone (4-MU), a derivative of coumarin, has been used as an approved drug to treat biliary spasm.
Recent publications have reported that 4-MU inhibits production of hyaluronan (HA), which is a key component of
extracellular matrix deposition in fibrotic and cirrhotic liver. We investigated the effect of 4-MU on fibrotic liver in
rats. Methods: Liver fibrosis was induced by bile duct ligation (BDL). Male Sprague-Dawley rats received a standard diet or the same diet containing 1% or 5% of 4-MU from 1 week before BDL. The rats were sacrificed at 3 weeks after BDL. Results: Administration of 4-MU increased serum 4-MU concentration levels, thereby decreasing serum HA levels in a dose-dependent manner. 4-MU treatment suppressed liver fibrosis in interlobular and pericentral areas with
reduced alpha-smooth muscle actin expression, which suggested hepatic stellate cell activation. Conclusion: Treatment with 4-MU suppressed the experimental hepatic fibrosis accompanied by inhibition of HA production. Although further experimental studies are needed, 4-MU could protect against fibrogenesis and may be
repurposed as a safe therapeutic application for hepatic fibrosis.
White zone visualized by magnifying endoscopy with narrow-band imaging (M-NBI) corresponds to stratified alignments of the gastric epithelium. In this study, we develop an image processing method for white zone with high sensitivity. Eleven specimens of endoscopic submucosal resection from 8 patients with gastric cancer were used. M-NBI was taken serially along the line of interest. The pictures were processed by low-pass filter for white zone area (%), and visually classified into the presence (WZ+) or absence of white zone (WZ-) by a single
endoscopist. The formalin-fixed-specimen was sliced along the same line of interest. The histological pictures was
processed for averaged epithelial area (μm×mm) at 1mm intervals. A total of 123 intervals were analyzed. In cancer, 36 intervals were visually classified as WZ- and 30 as WZ+. Averaged epithelial area and white zone area were
significantly lower in WZ- than in WZ+. But, in background, two variables did not significantly differ between WZand
WZ+. A total of 117 intervals had averaged epithelial area > 20 μm×mm and white zone area > 21.0 % with no correlation between two variables. Low-pass filter was found to visualize white zone in 41 intervals classified as WZ-.
Using a murine model, we investigated whether allogeneic umbilical cord blood cell (UCBC) transplantation facilitates immune reconstitution with functional maturity in comparison with bone marrow cell (BMC) transplantation. UCBCs and BMCs prepared from green fluorescent protein (GFP)-transgenic C57BL/6 (H-2b） mice were transferred into BALB/c (H-2d) mice that had been subjected to lethal total body X-ray irradiation.
Although UCBC-transplanted mice showed poorer survival than BMC-transplanted mice for the same number of
transplanted cells, increasing the number of transplanted UCBCs improved survival with an increase of donor-derived
GFP⁺ cell engraftment. Flow cytometric analysis revealed development of GFP⁺ immune cells of donor
origin, including T cells, B cells, monocytes, and granulocytes, in the peripheral blood of both sets of recipient mice.
Furthermore, the functional maturity of T and B cells involved in adaptive immunity following allogeneic UCBC- and
BMC-transplantation was assessed in T- and B-deficient RAG2-/-BALB/c mice. Both sets of recipients showed complete rejection of third-party C3H (H-2k) skin grafts and antibody responses to the T cell-dependent antigen, 2,4,6-trinitrophenyl-keyhole limpet hemocyanin, with immunoglobulin class switching. These results suggest that UCBCs have essentially the same ability as BMCs to reconstitute a functional adaptive immune system, even in an allogeneic environment.
This study evaluated stress experienced by rescue team members during a simulated search and rescue operation in a confined space and determine if wireless communication reduces stress. A total of 57 rescue team members of X prefecture participated. The stress visualization indices were ptyalin (i.e., salivary amylase), salivary cortisol, autonomic nervous system response, visual analog scale, and a short version of the profile of mood states.
The subjects were randomized to perform a simulated search in a confined space without or with communication, and the stress indices were compared between the two groups.
Stress was observed in the form of changes in ptyalin level, visual analog scale scores, and autonomic nervous system responses. Statistical analysis showed that the “with communication” group exhibited significantly lower stress than the “without communication” group. Thus, wireless communication is recommended to reduce the stress experienced by rescue team members working in confined spaces.