1 To study the role of interleukin (IL)-4 in the onset of contact hypersensitivity (CH) in mice, the e ect of IL-4 gene-depletion and anti-IL-4 monoclonal antibody treatment on dinitro¯uorobenzene (DNFB)-induced CH was examined. Simultaneously, to clarify the e ect of background gene, DNFB-induced CH in BALB/c and C57BL/6 mice was compared. 2 Five repeated topical applications of DNFB to the ears of mice resulted in CH of the ears in terms of increases in ear thickness and histopathological changes. The magnitude of ear thickness increase in BALB/c mice was almost three times greater than that in C57BL/6 mice. 3 The CH in BALB/c mice was signi®cantly suppressed by IL-4 gene-depletion and anti-IL-4 monoclonal antibody treatment. In contrast, the symptoms of dermatitis in C57BL/6 mice were slightly a ected by the same treatment. These changes corresponded well to the production of speci®c IgE antibody. 4 Total IgE antibody production and the expression of productive Ce mRNA were dramatically suppressed by IL-4 gene-depletion and anti-IL-4 treatment in BALB/c and C57BL/6 mice. Neither total IgG nor IgM levels in either strain of mice was altered by depletion of IL-4. 5 The expression of IFN-g in the skin lesion was dramatically suppressed by IL-4 gene-depletion in BALB/c mice, but not in C57BL/6 mice. 6 These ®ndings indicate that IL-4 plays an important role in the onset of DNFB-induced CH in BALB/c mice, but not in C57BL/6 mice.
The impact of preoperative malnutrition and sarcopenia on survival in oral squamous cell carcinoma (OSCC) patients remains controversial. We investigated the effects of the preoperative nutritional status and abnormalities in body composition on the mortality of OSCC patients. A retrospective study involving 103 patients with OSCC was conducted. Disease-specific survival (DSS) according to the preoperative psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) was evaluated. Univariate and multivariate analyses were performed to determine the predictive performance of the covariates with respect to DSS. The DSS rate in patients with high IMAC and low PMI was significantly lower than that in controls. Multivariate analysis revealed that a low preoperative Prognostic Nutritional Index (PNI) and high IMAC were independent risk factors. We demonstrated that preoperative malnutrition and abnormal body composition, such as preoperative skeletal muscle quality, are associated with DSS in OSCC patients. Our study suggests that the evaluation of preoperative malnutrition and skeletal muscle quality would be useful for predicting mortality in patients with OSCC.
Accumulating evidence has shown that sarcopenia in patients with oral squamous cell carcinoma (OSCC) is at a risk of poor prognosis. There is no universal consensus on how to assess sarcopenia in patients with OSCC in daily practice. It is important to validate the usefulness of sarcopenia assessment from cervical muscles, which are frequently used in routine clinical practice in patients with OSCC. In this study, we investigated whether preoperative lumbar (L3) skeletal muscle mass and adiposity in OSCC patients were associated with cervical (C3) skeletal muscle mass and adiposity from CT measurements. We also investigated whether skeletal muscle mass and adiposity in the C3 muscles were associated with survival rates in patients with OSCC. We demonstrated that both the quality and quantity of muscle between the C3 and L3 levels were positively correlated with each other. We also demonstrated that the survival rates in patients with low sternocleidomastoid muscle mass index, high processus spinosus muscle-intramuscular adipose tissue content, and the combination of both were significantly lower than those in the controls. These results suggest that the assessment of sarcopenia from multiple neck muscles by preoperative CT measurements may be useful in predicting the prognosis of patients with OSCC.
Myofibroblasts contribute to the healing of infarcted areas after myocardial infarction through proliferation, migration, and production of extracellular matrix (ECM). Expression of endostatin, a cleaved fragment of type XVIII collagen, increases in the heart tissue of an experimental myocardial infarction model. In the present study, we examined the effect of endostatin on the function of myofibroblasts derived from an infarcted area. The myocardial infarction model was created by ligating the left anterior descending artery in rats. Two weeks after the operation, α-smooth muscle actin (α-SMA)-positive myofibroblasts were isolated from the infarcted area. Endostatin significantly increased the proliferation and migration of myofibroblasts in vitro. On the other hand, endostatin had no effect on the production of type I collagen, a major ECM protein produced by myofibroblasts. Endostatin activated Akt and extracellular signal-regulated kinase (ERK), and the pharmacological inhibition of these signaling pathways suppressed the endostatin-induced proliferation and migration. A knockdown of the COL18A1 gene in the myocardial infarction model rats using small interference RNA (siRNA) worsened the cardiac function concomitant with wall thinning and decreased the α-SMA-positive myofibroblasts and scar formation compared with that of control siRNA-injected rats. In summary, we demonstrated for the first time that endostatin might be an important factor in the healing process after myocardial infarction through the activation of myofibroblasts.
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