The effects of long-term intake of a low concentration of sodium fluoride on bone loss in the growing senescence-accelerated mouse (SAM-P/6)]

The long-term effects of low concentrations of sodium fluoride (0, 1 and 5 mg/l) in drinking water on bone metabolism were examined in the growing senescence accelerated mouse (SAM-P/6) as a spontaneous experimental model of senile osteoporosis. In 4 and 8 months of age respectively, there were almost no differences in body weight, and serum calcium, phosphorus and alkaline phosphatase levels between controls and fluoride groups. Calcium contents per dry weight of femoral bone were higher in fluoride groups than in controls. The bone mass of the trabecular was not affected by the low-concentration sodium fluoride intake. However, sodium fluoride decreased the rate of bone mass loss associated with aging in the cortical bone in SAM-P/6 compared with the control. The results of this study suggest that, in growing SAM-P/6 mice, a long-term low-concentration sodium fluoride intake affects the skeletal metabolism.     

Treatment with aflatoxin B1 for immortalization of human fibroblasts from Li-Fraumeni patients

Immortalization of normal human fibroblasts is a very rare event. Multiple genes such as p53 and cellular senescence genes are possibly involved in immortalization of human fibroblasts, suggesting that multiple treatments with carcinogens are required for the immortalization. We describe here the procedure for immortalization of human fibroblasts (MDAH 087) from Li-Fraumeni cancer syndrome with a germ-line p53 mutation. The cells were subjected to multiple treatments with aflatoxin B₁ (AFB₁) in the presence of exogenous metabolic activation with rat liver post-mitochondrial supernatant (PMS), and 3 of 9 MDAH 087 cell cultures treated 1–3 times with 0.1–1 µg/ml AFB₁ became immortal, defined as continuous growth for over 300 population doublings after the first treatment. However, cultures of human fibroblasts from a normal embryo treated under the same conditions failed to escape senescence. The results indicate that the model of human fibroblasts with a mutated p53 allele exposed to AFB₁ is potentially useful for studying mechanisms of chemically induced immortalization.     

Radiation therapy in patients with unresectable hepatocellular carcinoma

From April 1978 through December 1989, a total of 17 patients with unresectable hepatocellular carcinoma (HCC) were treated with radiation therapy alone or radiation therapy in conjunction with percutaneous ethanol injection (PEI), transarterial infusion chemotherapy (TAI), or transarterial embolization (TAE) at the National Medical Center Hospital. The median survival of all patients was 13.8 months. The survival values determined at 1, 2, and 3 years were 58.8%, 26.1%, and 9.8%, respectively. Only the pretreatment liver function affected the survival value. Between patients who did not have liver cirrhosis (LC) as well as those who had LC of Child's class A and patients who had LC of Child's class B or C, the differences observed in the 1-year survival value and the median duration of survival were statistically significant (P<0.05). the=" serum=" cholinesterase=" (che)=" level=" seemed=" to=" be=" a=" good=" indicator=" of=" liver=" function=" during=" the=" radiation=" therapy.=" a=" field=" size=" of=" 150=">² and a total dose of 5000 cGy (TDF 82) seemed to be well tolerated by patients who did not have LC and those who had LC of Child's class A. The field size determined whether patients with poor liver function such as LC of Child's class B or C would develop severe hepatic deterioration after undergoing radiation therapy.Presented at The Second International Symposium on Treatment of Liver Cancer. Taipei, 3–4 February 1991     

Diagnostic and predictive performance and standardized threshold of traditional biomarkers for drug‐induced liver injury in rats

Traditional biomarkers such as alanine and aspartate aminotransferase (ALT, AST) and total bilirubin (TBIL) have been widely used for detecting drug‐induced liver injury (DILI). Although the Food and Drug Administration (FDA) proposed standardized thresholds for human as Hy's law, those for animals have not been determined, and predictability of these biomarkers for future onset of hepatic lesions remains unclear. In this study, we investigated these diagnostic and predictive performance of 10 traditional biomarkers for liver injury by receiver‐operating characteristic (ROC) curve, using a free‐access database where 142 hepatotoxic or non‐hepatotoxic compounds were administrated to male rats (n = 5253). Standardization of each biomarker value was achieved by calculating the ratio to control mean value, and the thresholds were determined under the condition of permitting 5% false positive. Of these 10 biomarkers, AST showed the best diagnostic performance. Furthermore, ALT and TBIL also showed high performance under the situation of hepatocellular necrosis and bile duct injury, respectively. Additionally, the availability of the diagnostic thresholds in difference testing facility was confirmed by the application of these thresholds to in‐house prepared dataset. Meanwhile, incorrect diagnosis by the thresholds was also observed. Regarding prediction, all 10 biomarkers showed insufficient performance for future onset of hepatic lesions. In conclusion, the standardized diagnostic thresholds enable consistent evaluation of traditional biomarkers among different facilities, whereas it was suggested that novel biomarker is required for more accurate diagnosis and prediction of DILI. Copyright © 2014 John Wiley & Sons, Ltd.     

Polymorphism and haplotype analysis of three novel short tandem repeat loci in the p11.4 region of human X chromosome

International Journal of Legal Medicine - X-chromosomal short tandem repeats (X-STRs) are useful for the identification of absent single parents and complex blood relations. In the present study,...     

Dialysate Vascular Endothelial Growth Factor Is an Independent Determinant of Serum Albumin Levels and Predicts Future Withdrawal From Peritoneal Dialysis in Uremic Patients

Peritoneal protein loss due to high peritoneal permeability may contribute to hypoalbuminemia and early withdrawal from peritoneal dialysis (PD) therapy in end stage renal disease (ESRD) patients. We have found that pigment epithelium‐derived factor (PEDF) has anti‐vasopermeability properties both in cell culture and animal models by counteracting the biological actions of vascular endothelial growth factor (VEGF). However, it remains unknown which clinical variables, including dialysate VEGF and PEDF, are associated with decreased serum albumin levels and could predict early withdrawal from the PD in ESRD patients. We address these issues. Twenty‐seven ESRD patients undergoing PD were enrolled. Clinical variables were measured at 6 months after commencing PD. We examined the independent correlates of serum albumin in PD patients and then prospectively investigated the predictors of withdrawal from the PD therapy over 4 years. Dialysate VEGF was associated with peritoneal solute transport rate (P = 0.002), serum albumin (inversely, P < 0.001) and dialysate PEDF levels (P < 0.001). In multiple stepwise regression analysis, age (P = 0.002) and dialysate VEGF levels (P < 0.001) were independent determinants of serum albumin levels. High VEGF (>27 pg/mL), low serum albumin (≤3.31 g/dL) and low hemoglobin (≤11.2 g/dL) were correlated with withdrawal from the PD therapy during the 4 years. The odds ratio of dialysate VEGF for early withdrawal from the PD was 6.310 (P = 0.035). The present study demonstrated that increased dialysate VEGF was associated with decreased serum albumin and early withdrawal from the PD therapy. Inhibition of peritoneal VEGF production may be a therapeutic target in PD patients.     

EARLY GASTRIC CANCER WITH WIDESPREAD DUODENAL INVASION WITHIN THE MUCOSA

We report a rare case of early gastric cancer confined to the mucosal layer with extensive duodenal invasion, curatively removed with distal gastrectomy. An 84‐year‐old Japanese woman was referred to our hospital with gastric cancer. A barium meal examination and esophagogastroduodenoscopy revealed an irregular nodulated lesion measuring 6.5 x 5.5 cm in the gastric antrum and an aggregation of small nodules in the duodenal bulb. A biopsy specimen showed well‐differentiated adenocarcinoma. The patient underwent distal gastrectomy with partial resection of the duodenal region containing the tumor and regional lymph node dissection, with no complication. Histological examination of the resected tissue confirmed well‐differentiated adenocarcinoma limited to the mucosal layer and without lymph node metastasis. The cancer extended into the duodenum as far as 38 mm distant from the pyloric ring, and the resected margins were free of cancer cells. Gastric cancer located adjacent to the pyloric ring thus has the potential for duodenal invasion, even when tumor invasion is confined to the mucosal layer. In such cases, care should be taken during examinations to detect duodenal invasion, and the distal surgical margin must be negative given sufficient duodenal resection.     

Recurrence of gastric cancer in the jejunal pouch after completion gastrectomy

We herein present a case of recurrence of gastric cancer in the jejunal pouch after total gastrectomy in a 74-year-old man. He had a history of two operations for gastric cancer. The second operation was a completion gastrectomy with jejunal pouch reconstruction and regional lymphadenectomy, for gastric cancer in the cardia of the remnant stomach, performed 2 years and 9 months before the present admission. A follow-up endoscopy showed three elevated tumors along the suture lines in the jejunal pouch in the upper digestive tract. Resection of the jejunal pouch was performed. Gross pathological examination revealed elevated lesions along the staple suture lines in the jejunal pouch. Histopathologically, moderately differentiated tubular adenocarcinoma involving the muscular layer, without lymphatic metastases, was recognized. Recurrence of gastric cancer in the jejunal pouch after resection is rare. We suggest that implantation of exfoliated cancer cells gave rise to the recurrence of tumors on the suture line in this patient. We also review two cases of gastric cancer in the jejunal pouch after resection previously described in the literature.