Mutations of p53 in morphologically non-neoplastic mucosa of long-standing ulcerative colitis.

Two cases of ulcerative colitis (UC)-associated carcinoma or dysplasia and morphologically non-neoplastic mucosa with p53 protein overexpression (MNNM-p53OE) were selected. DNA was extracted from the paraffin blocks of these lesions and exons 5 - 8 of the p53 gene were analyzed by PCR and direct sequencing. In addition, mutations in K-ras codon 12 were analyzed by PCR-RFLP methods. MNNM-p53OE was located surrounding and adjoining a coexisting carcinoma and / or dysplasia. A p53 mutation was detected in 12 / 22 (54.5%) MNNM-p53OE samples, 4 / 8 (50%) dysplasia samples and 8 / 8 (100%) carcinoma samples. The p53 mutations detected in MNNM-p53OE were identical to those demonstrated in the adjoining carcinoma and / or dysplasia. No K-ras codon 12 mutation was detected in any of the samples. These results indicate that MNNM-p53OE may share an identical clonal linkage with a coexisting carcinoma and / or dysplasia, and may be an initial and submorphological form of UC-associated neoplasia. Recognition of MNNM-p53OE in biopsy specimens may help to identify patients with UC at risk of developing colorectal carcinoma.     

Use of ultrasonography to measure liver size in children

We used a real-time, ultrasound scanner to establish a reference interval of liver size in children based on their height and age. The study group comprised 476 children ranging in age from 1 month to 15 years. Maximal craniocaudal length (L1) and anteroposterior width (L2) determined in the longitudinal plane passing through the aorta were used as parameters for size of the anatomical left lobe; for the anatomical right lobe the shortest distance between the anterior, surface of the liver and the midpoint of the horizontal portion of the portal vein (R1) and the distance between the midpoint of the horizontal portion of the portal vein and the deepest phrenic surface (R2) determined by the right subcostal approach were used. The strongest correlation obtained was between height and the sums L1+L2 and R1+R2. Because the liver naturally enlarges as children grow, this reference should prove useful in evaluating hepatic size in children of all ages.     

Anti-tumor effects of water-soluble propolis on a mouse sarcoma cell line in vivo and in vitro

The honeybee product propolis and its extracts are known to have biological effects such as antibiotic, anti-viral, anti-inflammatory and anti-tumor activities. This study was designed to investigate whether water-soluble propolis (WSP) inhibits tumor growth. The tumor cell line used was mouse sarcoma 180 (S-180), and its growth was determined in vitro and in vivo with exposure to different concentrations of WSP. The effects of WSP on tumor cells in vitro were evaluated by measuring the intracellular uptake of 3H-thymidine. 3H-thymidine uptake was inhibited in accordance with the concentration of WSP. The minimum concentration of WSP necessary for 3H-thymidine uptake inhibition was 1.0 microg/ml and uptake was suppressed to 88% of the level in non-treated cells at this concentration. In an experiment using tumor-bearing mice, oral administration of WSP was begun 24 hours after transplantation of S-180 cells. WSP was administered to the mice 5 times, every other day for 10 days. The doses were 320 mg/kg (10 mg/mouse) or 960 mg/kg (30 mg/mouse) of body weight. All mice were sacrificed 10 days after transplantation, and tumor growth was evaluated. The orally administered WSP significantly inhibited the growth of transplanted tumors (p < 0.05). Furthermore, histological findings revealed a significant reduction in mitotic cells and tumor invasion of the muscular tissue at both dose-levels of WSP.     

Pancreaticobiliary maljunction: pathophysiological and clinical aspects and the impact on biliary carcinogenesis

BACKGROUND: Pancreaticobiliary maljunction (PBM) is frequently associated with congenital choledochal cyst (CCBD), but differs in embryonic cause and clinical features. It is thought to develop as a misarrangement of the embryonic connections in the pancreaticobiliary ductal system, with the terminal bile duct joined to one of the ducts of the ventral pancreas. Clinical aspects are intermittent abdominal pain, relapsing acute pancreatitis, jaundice, cholangitis, and gallbladder cancer. In patients with PBM and CCBD, primary bile duct stones, acute cholangitis, and bile duct cancer are considered to result from cholestasis, regurgitation of pancreatic juice, and reciprocal reflux of bile and pancreatic juice. The mixture of bile and pancreatic juice due to recipocal reflex very likely plays an important role in biliary carcinogenesis. PATIENTS AND METHODS: We reviewed the pathophysiological and clinical aspects and biliary carcinogenesis in 250 PBM patients (169 with benign hepatobiliary and pancreatic disease, 81 with malignancy). RESULTS: PBM patients show elevated cellular proliferation activity in the gallbladder epithelia. A number of oncogenes and tumor suppressor genes have been identified and implicated in carcinogenesis, particularly the K- ras oncogene and the p53 suppressor gene. Some K- ras mutations do not appear essential for hyperplasia but may be an early event in carcinogenesis. The p53 mutations are involved in carcinogenesis in the biliary epithelium in PBM patients.     

Effectiveness of subarachnoid drug infusion for pediatric tumor‐related pain

Although the effectiveness of subarachnoid continuous drug infusion has been established in cancer pain management, its clinical use in children is rare. A 14‐year‐old girl with neurofibromatosis type I complained of right leg pain stemming from a growing tumor on her right buttock. Continuous and breakthrough right leg pain were unbearable, even at high doses of systemic opioids that caused severe constipation and deep sedation. Subsequent continuous infusion of bupivacaine and morphine through a subarachnoid catheter effectively relieved the girl's pain. The corresponding decrease in systemic opioid also improved her activities of daily living. The patient eventually died of cachexia due to the rapidly growing buttock lesion that was pathologically confirmed post‐mortem as a malignant peripheral nerve sheath tumor. Subarachnoid continuous drug infusion may be very useful in controlling severe pain with few side‐effects, even in the field of pediatric palliative care.     

Two proliferation-related proteins, TYMS and PGK1, could be new cytotoxic T lymphocyte-directed tumor-associated antigens of HLA-A2+ colon cancer.

PURPOSE: The purpose of this work was to provide a scientific basis for specific immunotherapy of colon cancer. EXPERIMENTAL DESIGN: This study focused on identification of colon tumor-associated antigens and HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes (CTLs) generated from tumor-infiltrating lymphocytes of a colon cancer patient. A gene expression cloning method was used to identify genes coding for tumor antigens. Fifty-six peptides with HLA-A2-binding motifs encoded by these proteins were examined for their ability to induce HLA-A2-restricted and tumor-reactive CTLs. RESULTS: We identified the following three genes coding for proliferation-related proteins: thymidylate synthase (TYMS), which is involved in chemoresistance (5-fluorouracil); 5'-aminoimidazole-4-carboxamide-1-beta-d-ribonucleotide transfolmylase/inosinicase (AICRT/I); and phosphoglycerate kinase 1 (PKG1), which was secreted by tumor cells and involved in the angiogenic process. TYMS was preferentially expressed in tumor cells, whereas AICRT/I and PKG1 were equally expressed in both cancer cells and normal tissues at the mRNA level. Among 56 peptides with HLA-A2-binding motifs encoded by these proteins, 8 peptides were recognized by the CTLs, and 5 of 8 peptides were also recognized by the CTL precursors without ex vivo activation in the peripheral blood of colon cancer patients. Furthermore, four of them (one each from TYMS and PKG1 and two from AICRT/1) possessed the ability to induce HLA-A2-restricted and peptide-specific CTLs cytotoxic to colon tumor cells in peripheral blood mononuclear cells of colon cancer patients. CONCLUSIONS: TYMS and PGK1, as well as their epitope peptides, might be appropriate target molecules for specific immunotherapy of HLA-A2(+) colon cancer patients because of the positive role of TYMS and PGK1 in chemoresistance (5-fluorouracil) and angiogenesis of tumor cells, respectively.     

Single-stage repair for ascending aortic aneurysm,artery stenosis and occlusion of neck vessels caused by Takayasu arteritis

Takayasu arteritis results in a variety of vascular symptoms, and there are some cases in which progressive vascular lesions require surgical intervention. We present a case with ascending aortic aneurysm, right common carotid artery stenosis, left common carotid artery occlusion and left subclavian artery stenosis caused by Takayasu arteritis that was successfully treated with total arch replacement and ascending aorta to right internal carotid artery bypass.     

Enhanced and inhibited biotransformation of methyl mercury in the rat spleen

Biotransformation of methyl mercury in rats was studied by enhancing or inhibiting its biotransformation with various procedures. A new sensitive method developed to determine specifically inorganic mercury in the presence of organic mercury was used. Biotransformation was enhanced by treating the rat with phenylhydrazine. The increase of inorganic mercury was highest (four to five times) and rapid in the spleen. Inhibited biotransformation of methyl mercury was observed in splenectomized rats. The inorganic portion of total mercury in the macrophage-rich fraction of spleen cells was clearly higher than that in unfractionated spleen cells. The biotransformation of methyl mercury was inhibited by treating the rat with carrageenan, a well-known substance blocking macrophage function. These results suggest that the spleen is an important site for the formation of inorganic mercury, and that the macrophage participates in this biotransformation.     

TiO2粉体对小鼠主要脏器中微量元素影响

随着纳米科技和制备技术的发展,纳米材料被广泛应用于材料、化妆品、医药和化工等众多领域^〔1,2〕,而纳米材料的超微性,使之理化性质与普通颗粒污染物相比发生了根本性改变,有可能导致生物效应性质和强度的改变。同样质量浓度下,纳米粒子将比微米粒子的数量多且活性高,纳米粒子能够进入生物体内微米级颗粒材料所不能抵达的区域,与细胞发生反应的机会更大,纳米粒子将对机体产生比普通颗粒污染物更大的影响^〔3,4〕。而迄今为止世界各国尚未制定出针对纳米材料特性的安全评价标准和劳动保护条例。目前,国内外已经进行了部分纳米粒子在动物体内的吸收、分布和排泄的研究,但关于纳米粒子在人体内的生物转运及其机制的研究较少。