Kir6.2 E23K polymorphism is related to secondary failure of sulfonylureas in non‐obese patients with type 2 diabetes

Aims/Introduction

The Kir6.2 E23K polymorphism was studied with a special reference to secondary sulfonylurea (SU) failure in non‐obese patients with type 2 diabetes.

Materials and Methods

We recruited 278 non‐obese (body mass index ≤30.0 kg/m²) Japanese patients with type 2 diabetes who had a history of SU treatment (for 11.2 ± 6.3 years) and compared the frequency of the secondary SU failure among the genotypes of the polymorphism. Genotyping of the Kir6.2 E23K was carried out by polymerase chain reaction‐restriction fragment length polymorphism.

Results

The genotype frequencies of the polymorphism were similar to those previously reported in Japanese patients with type 2 diabetes. The frequency with which patients deteriorated into secondary SU failure was significantly higher in those with the KK genotype than those with EE or EK genotypes. Among 214 patients who eventually received insulin therapy because of secondary SU failure, the period of SU treatment in those with the KK genotype was significantly shorter than those with the EE or EK genotype, although the period from diagnosis to the start of SU treatment was not significantly different.

Conclusions

These data suggest that the Kir6.2 E23K polymorphism is related to the acceleration of secondary SU failure in non‐obese Japanese patients with type 2 diabetes.     

Intra-articular nodular fasciitis of the knee: a rare cause of recurrent hemarthrosis

A 20-year-old man presented with pain and recurrent hemarthrosis in the right knee. Magnetic resonance imaging of the knee showed a lesion with homogeneous low signal intensity on T1-weighted images and a heterogeneous, low to high signal intensity on T2-weighted images. At arthroscopy, the mass was located between the posterior cruciate ligament and the posterior knee joint capsule. The tumor was excised through a posterior approach and histologically diagnosed as a nodular fasciitis. Intra-articular nodular fasciitis is a very rare clinicopathologic entity. The current case showed the unique clinical feature of recurrent hemarthrosis at initial presentation, which has not been previously reported.     

Diabetes mellitus not an unfavorable factor on the prognosis of hepatitis C virus‐related hepatocellular carcinoma

Aim

Diabetes mellitus (DM) is a potential risk factor for hepatocarcinogenesis, especially in patients with hepatitis C virus (HCV) infection. We aimed to elucidate whether DM influences the surgical outcomes of patients with hepatocellular carcinoma (HCC).

Methods

Our patients were routinely controlled to keep urinary glucose excretion to less than 3.0 g/day before surgery, and the serum glucose level under 200 mg/dL after surgery. The surgical outcomes and postoperative complications of 112 patients with HCV‐related HCC with DM (DM group) were compared to those of 112 propensity‐matched patients without DM (non‐DM group).

Results

After a median follow‐up of 3.2 years (range, 0.2–11.3 years), the median overall (5.2 years; 95% confidence interval, 3.8–6.5 years) and recurrence‐free survival (2.2 years; 1.7–2.9 years) in the DM group were not significantly different from those (6.3 years; 5.4–7.1 years, P = 0.337; and 2.2 years; 1.7–3.6 years, P = 0.613) in the non‐DM group. The independent factors related to overall survival were the background liver (hazard ratio, 2.06; 95% confidence interval, 1.27–3.39, P = 0.014) and tumor differentiation grade (2.07; 1.14–4.05, P = 0.015). Thirty‐two patients (28.5%) in the DM group and 32 patients (28.5%) in the non‐DM group had morbidities after operation, with no significant difference between the groups (P = 1.000). Furthermore, postoperative control status of DM did not affect the prognostic outcome.

Conclusion

Diabetes mellitus does not affect the surgical outcomes of patients with HCV‐related HCC, and it is not an unfavorable factor when selecting candidates for liver resection of HCC.     

Serum adiponectin is associated with fasting serum C-peptide in non-obese diabetic patients

Circulating adiponectin (ADP) level in diabetic patients was mainly studied from a viewpoint of insulin action, with little being known about the regulation by pancreatic beta-cell function. We thus investigated the relationship between the serum ADP concentration and pancreatic beta-cell function in non-obese [body mass index (BMI) <30 kg/m(2)] diabetic patients. Serum ADP was measured in 239 type 2 diabetic patients, 61 type 1 diabetic patients and 159 non-obese and non-diabetic subjects with enzyme-linked immunosorbent assay. Serum ADP was analyzed separately by gender. In both males and females, the ADP level increased in conjugation with beta-cell dysfunction, estimated by fasting serum C-peptide, and showed marked increase in type 1 diabetic patients. Multivariate analysis in type 2 diabetic patients showed that the fasting serum C-peptide was extracted as an independent and significantly negative modulator for serum ADP in addition to BMI. The ADP level was not associated with the daily dose of injected insulin in the multivariate analysis using insulin treated patients with types 1 and 2 diabetes. These results indicate that pancreatic beta-cell function is one of a significant negative modulator for the circulating ADP level in non-obese diabetic patients and support the presence of an adipoinsular axis.     

Combination adoptive immunotherapy with chemoradiotherapy in oral carcinomas

Background The antitumor effects of adoptive immunotherapy in combination with chemoradiotherapy were investigated in patients with oral squamous cell carcinoma. Methods Inductive chemoradiotherapy with peplomycin, 5-fluorouracil and⁶⁰Co was given to 56 patients [CRI(−)group]. A local injection of adoptive lymphokine-activated killer (LAK) cells (≈2×10⁸ cells) and small doses of interleukin-2(≈3×10⁵ U) and interferon-gamma (≈2×10⁵U) was given to 40 other patients in combination with the chemoradiotherapy [CRI(+) group]. Results Clinically, CR, PR, and LR were observed in 15 (37.5%), 24 (60.0%), and 1 (2.5%) of the patients in the CRI (+) group, respectively; and in 14 (25.0%), 38 (67.9%), and 4 of the patients (7.1%) in the CRI (−) group. The histopathological effects were correlated with the tumor remission rate, with lethal degeneration (grades III and IV), and prominent degeneration (grade IIB) in the tumor cells noted in 20 (50.0%) and 16 (40.0%) of the CRI(+) patients, respectively; and in 21 (37.5%) and 29 (51.8%) of the CRI (−) patients. Immunohistochemically, a prominent decrease of proliferating cell nuclear antigenpositive cells with a reciprocal increase of Le^Y-positve cells was induced by the chemoradioimmunotherapy. DNA fragmentation was observed in the mutant type p53-negative tumors in the CRI(+) group. Conclusion Adoptive immunotherapy with LAK cells and cytokines in combination with chemoradiotherapy induces advantageous anticancer effects resulting from necrosis and apoptosis.     

细胞角蛋白(CK)13及其基因在术后性上颌囊肿衬里上皮中的表达

目的研究CK13蛋白和CK13-mRNA在术后性上颌囊肿(post operative maxillary cysts,POMCs)衬里上皮细胞中的表达,进而探讨CK13在纤毛柱状上皮向鳞状上皮化生过程中的意义.方法本研究采用免疫组织化学染色法和RT-PCR法分别检测CK13蛋白和CK13-mRNA在32例POMCs衬里上皮中的表达.结果免疫组织化学染色显示CK13蛋白在鳞状上皮中呈阳性表达,在纤毛柱状上皮中呈阴性;RT-PCR法检测出CK13-mRNA在所有囊肿衬里上皮均呈阳性表达,其中13例纤毛柱状上皮呈弱阳性,14例既有纤毛柱状上皮又有鳞状上皮的混合上皮呈中等强度表达,5例鳞状上皮呈强阳性.结论 POMCs衬里的纤毛柱状上皮中存在CK13-mRNA,提示化生的鳞状上皮细胞可能来源于纤毛柱状上皮.在纤毛柱状上皮向鳞状上皮化生时CK13蛋白可能起着重要作用.     

Tetraspanin gene expression levels as potential biomarkers for malignancy of gingival squamous cell carcinoma

Accurate assessment of malignancy in oral squamous cell carcinoma is essential to optimize treatment planning. To detect a biomarker related to malignant propensity in gingival squamous cell carcinoma (GSCC), quantitative gene expression analysis of tetraspanin family genes was conducted. In 73 cases of GSCC, total RNA was extracted from carcinoma tissues, and gene expression was analyzed by quantitative real time‐PCR. Six tetraspanin family genes (CD9, CD63, CD81, CD82, CD151, NAG‐2) were investigated. Housekeeping genes (ACTB and GAPDH), anchor protein genes (JUP and PXN) and an integrin gene (ITGA3) were used as reference genes. Forty‐five gene expression ratios were calculated from these 11 gene expression levels and were analyzed with clinical parameters using multivariate statistical methods. According to the results of the logistic regression analysis subjecting cervical lymph node metastasis as a target variable, CD9/ACTB (p = 0.013) or CD9/CD82 (p = 0.013) in addition to tumor size (p = 0.028) were detected as significant factors. In Cox proportional hazards regression analysis, delayed cervical lymph node metastasis (p = 0.039) and tumor cell positive surgical margin (p = 0.032) in addition to CD151/GAPDH (p = 0.024) were detected as significant factors for death outcome. A Kaplan‐Meier survival curve presented a significantly lower survival rate of the group with a CD151/GAPDH value of 10 or more (log rank and generalized Wilcoxon tests: p = 0.0003). Results of this study present the usefulness of CD9 and CD151 expression levels as biomarkers for assessment of malignancy in GSCC. They also indicate that detection of residual tumor cells at the surgical margin and the biological malignancy of a tumor interdependently affects prognosis. © 2009 UICC     

Cytokeratin expression patterns in jaw cyst linings with metaplastic epithelium

BACKGROUND: Cytokeratin (CK) expression patterns have been studied in numerous intact and diseased oral tissues. However, CK expression in metaplastic squamous cells has not been explored in depth and the origin of metaplastic epithelial linings of the jaw cysts has not been sufficiently investigated. METHODS: We examined CK expression in 46 postoperative maxillary cysts (POMCs) which were lined with pseudostratified columnar cells only, columnar and squamous cells, and squamous cells only, in 13, 30 and 3 cases, respectively. RESULTS: The expression of CK8, CK13 and CK18 were observed in 39, 9 and all 43 of the columnar epithelial linings, respectively. Metaplastic squamous epithelia expressed more CK13, and less CK18 and CK8. Of the 33 metaplastic linings, 24 expressed CK8, 23 CK13 and 26 linings expressed CK18. The patterns of expression of CK13 and CK18 observed were CK18(+)-CK13(-) in 10 metaplastic linings, CK18(+)-CK13(+) in 16, and CK18(-)-CK13(+) in 7. The expression of CK13- and CK18-mRNA was generally correlated with level of protein expressed. CK18-mRNA expression was observed by in situ hybridization, not only in the 26 metaplastic linings which were positive for CK18 protein, but also in five of the seven metaplastic linings which did not express CK18 protein. In addition, RT-PCR revealed an expression of CK18-mRNA in all metaplastic squamous linings, although the expression level was weaker than that in the columnar epithelial linings. The CK13-mRNA was expressed inversely to the CK18-mRNA. CONCLUSIONS: These results indicate that CK18-mRNA is preserved through metaplasia, although the protein expression decreased. Metaplastic squamous cells differentiate with a decrease of CK18 and an increase of CK13 expression.     

三叉旁核内含P物质的三叉神经初级传入终末的电镜研究

作用辣根过氧化物酶跨节追踪结合包埋后胶体金免疫电镜技术方法，对三叉旁核内含Ｐ物质的三叉神经初级传入终末形态和突触构筑进行了观察，这类终末大多较细，主要与树突和树突棘构成突触联系，另外，作还区分了三叉旁核内不含Ｐ物质的三叉神经初级传入终末以及含Ｐ物质的非三叉神经终末，上述结果提示三叉旁核可能感受与感合经不同类型终末传入的痛与非痛性感觉信息。