Effective production of dehydro cyclic dipeptide albonoursin exhibiting pronuclear fusion inhibitory activity. I. Taxonomy and fermentation

Strain KO-23, an actinomycete producing albonoursin as well as streptopyrone, was identified as Streptomyces albulus by morphological and biochemical studies. Fermentation conditions for albonoursin, a dehydro cyclic dipeptide exhibiting a pronounced inhibitory activity toward pronuclear fusion of sea urchin eggs, were optimized. Under the optimum conditions, the actinomycete produced 16 mg/liter of albonoursin, 30 times higher than that in the original culture. The cells cultivated under these conditions highly express biosynthetic enzymes for albonoursin, and thus are available for biosynthetic studies of dehydro cyclic peptides.     

Role of antioxidant systems in human androgen-independent prostate cancer cells

BACKGROUND: Most prostate cancer cells respond to initial hormonal therapy; however, some of them eventually acquire resistance to the hormonal therapy. Hormone-independent prostate cancer usually exhibits resistance to chemotherapy and radiotherapy. Antioxidant systems are known to be involved in the resistance of cancer cells to chemotherapy and radiotherapy. Therefore, it is of significance to examine antioxidant systems of hormone-independent prostate cancer for enhancing the efficacy of cancer therapy. METHODS: Three cell lines of human hormone-independent prostate cancer (PC-3, PC-3 MA2, and HPC36M) were examined for activities of superoxide dismutase, catalase, and glutathione peroxidase, and for levels of protein and nonprotein thiols such as metallothionein, glutathione, and thioredoxin. Sensitivity of these cells to anticancer drugs and inducers of reactive oxygen species such as paraquat, tert-butylhydroperoxide, and hydrogen peroxide was determined by microtiter assay. RESULTS: PC-3 and PC-3 MA2, which were derived from bone metastases, were resistant to paraquat, hydrogen peroxide, and cisplatin compared with HPC36M, which was obtained from the primary prostate cancer. However, HPC36M was resistant to vinblastine compared with PC-3 and PC-3 MA2. Both PC-3 and PC-3 MA2 had higher activities of catalase and glutathione peroxidase and higher levels of glutathione and metallothionein than HPC36M. CONCLUSIONS: These data suggest that enhanced ability in scavenging free radicals by antioxidant enzymes and thiol compounds may, at least in part, contribute to the resistance of bone metastatic prostate cancer during chemotherapy.     

Perioperative Nutrition and Metabolism in Pediatric Patients

Abstract A developing child, with a high metabolic rate and low body stores of nutrients, is susceptible to metabolic disturbances due to surgical stress. For perioperative nutritional care of infants, the distinct physiologic features of their body fluids must be carefully considered. The postoperative metabolic response is the same as that in adults, but in children this response is more rapid. Based on the urinary excretion of 3-methylhistidine in infants, the postoperative degradation of muscle protein is thought to be twice the preoperative level. This transient increase during the early postoperative period was not suppressed by increased amino acid intake, and energy intake was sufficient. To prevent postoperative metabolic complications, the energy intake of glucose or fat should correspond to the patient—s requirements, and excess carbohydrate should be avoided. The quantity and quality of the amino acid formula used must be carefully evaluated. E-pub: 31 October 2000     

Pyloric motor abnormality in patients with infantile hypertrophic pyloric stenosis

There are no published data of manometric studies of pyloric motor function in patients with infantile hypertropic pyloric stenosis (IHPS). The present study attempted to examine the characteristics of motor abnormality of the pylorus in five children with IHPS. Using a transducer-built-in manometric catheter cannulated through the pylorus under fluoroscopy, the pressure in the pyloric canal was recorded continuously over 3 h during fasting. Clusters of high-amplitude spastic contractions of over 300 mmHg were recorded at intervals. The frequency was 1–3/min (mean 1.7 cpm) and the duration was 7–15 s. These periodic spastic contractions were suppressed temporarily for 20–30 min after intravenous injection of 0.01 mg/kg atropine. After pyloromyotomy, these spastic contractions decreased remarkably in amplitude, but there were no changes in frequency. It is concluded that the underlying motor abnormality observed in hypertrophied pyloric muscle is clusters of high-amplitude contractions, although more precise measurements of basal pyloric pressure are needed to explore the pathophysiology of IHPS in detail. The effect of pyloromyotomy may be related to the decrease in high-amplitude contractions. Accepted: 26 May 1998     

Total parenteral nutrition-associated intrahepatic cholestasis in infants: 25 years' experience

BACKGROUND/PURPOSE: There are few long-term chronological reviews examining the incidence of total parenteral nutrition (TPN)-associated intrahepatic cholestasis (TPNAC) in infants. The authors therefore reviewed TPNAC in their 25-year series, and also looked at the current problems associated with TPN in infants. METHODS: Two hundred seventy-three surgical neonates who received TPN for more than 2 weeks were divided into 3 groups chronologically: group A (1971 through 1982, n = 77), group B (1983 through 1987, n = 72), and group C (1992 through 1996, n = 124). TPNAC was defined as serum direct bilirubin (DB) level greater than 2.0 mg/dL during the neonatal period. RESULTS: The incidence of TPNAC in groups A, B and C was 57%, 31%, and 25% (P< .01), respectively, and the mortality rate from TPN-associated complications was 13%, 3%, and 3% (P< .05), respectively. Over the last 5 years, severe TPNAC developed in 20 patients (16%). Four of 20 died of TPN-associated sepsis with hepatic failure; 2 had hypoganglionosis with intractable stagnant enteritis and subsequent sepsis, and 2 had fatal respiratory or cardiac disease. CONCLUSIONS: The incidence of TPNAC in surgical neonates and TPN-associated mortality rates have decreased significantly. The mortality rate, however, still remains at 3%. Two of 4 fatal cases had hypoganglionosis, which were totally dependent on TPN. In patients who require long-term TPN, TPN still has unsolved problems, and small bowel transplantation may be indicated.     

Measurement of serum hyaluronic acid as a sensitive marker of liver fibrosis in biliary atresia

PURPOSE: The aim of this study was to clarify whether serum hyaluronic acid level (SHA) can reflect the degree of liver fibrosis in biliary atresia (BA). METHODS: SHA was measured in 44 postoperative BA patients at 7 months to 22 years of age, with sandwich enzyme method (Hy-A 100 kit). SHA was compared with T.Bil (group 1, T Bil < 2; group 2, 2 < or = T Bil < 5; group 3, T Bil > or = 5 mg/dL), fibrosis score (0-6, the number of abnormal values among Alb, PT, ChE, T Chol, Fischer's ratio, prealbumin), and histologic grading (0-IV). RESULTS: SHA was 499.8 +/- 332.5 in group 3, significantly higher than in the control, group 1, or group 2. As fibrosis score rose, SHA became higher, and SHA in Score 6 (430.1 +/- 366.1 ng/mL) and score-5 (172.9 +/- 141.8 ng/mL) was significantly higher than in the control and other scores, respectively. As the histologic grade rose, SHA became higher, and SHA in grade IV (444.8 +/- 323.5 ng/mL) and grade III (166.0 +/- 70.3 ng/mL) was significantly higher than in the control or other Grades. Serial change of SHA since before HPE was parallel to the clinical course in 8 patients. CONCLUSION: SHA may be a useful serum marker reflecting the degree of liver fibrosis in BA.     

Maternal selenium deficiency enhances the fetolethal toxicity of methyl mercury

The effect of maternal selenium deficiency on methyl mercury fetotoxicity was examined in the ICR strain of mice. Pregnant mice were fed either selenium-deficient diets based on torula yeast or selenium-supplemented diets which were identical to the former except that 0.1, 0.2, or 0.4 mg of selenium per kilogram of diet was added as sodium selenite. Fetolethality of methyl mercury was exacerbated by maternal selenium deficiency when mothers were administered sc 15, 25, or 35 mumol/kg/day of methylmercuric chloride (MMC) on the 13, 14, and 15th days of pregnancy. One-tenth part per million of selenium in the diet was sufficient to protect the fetuses against MMC fetolethality when dams were administered 25 mumol/kg/day of MMC. Mercury concentrations in maternal and fetal tissues were independent of the dietary selenium level. Selenium concentration and glutathione peroxidase (GSH-Px) activity in maternal tissues were unaffected by MMC administration. In fetal liver, on the other hand, selenium concentration was increased and GSH-Px activity was decreased concurrently by maternal MMC administration in the selenium-supplemented groups. Therefore, as far as GSH-Px activity was concerned, the bioavailability of selenium was markedly decreased in fetal liver by maternal injection of MMC. The increase in selenium content in fetal liver, which was observed only in the selenium-supplemented groups, may play an important role in protection against fetolethal toxicity of MMC.     

Triiodothyronine generation from thyroxine in human thyroid: enhanced conversion in Graves' thyroid tissue

Conversion of T4 to T3 was studied in normal, Graves', and neoplastic thyroid tissues obtained at surgery. Homogenates of human thyroid follicular adenoma and carcinomas were incubated with [125I]T4 and dithiothreitol (DTT) at 37 C for 60 min under N2 gas. T3 formation was assessed by measuring [125I]T3 formed, using paper chromatography. In the second series of experiments, the suspensions of the 100,000 X g pellet of normal thyroid tissues adjacent to the tumor and Graves' thyroid tissues were incubated with unlabeled T4 and DTT at 37 C for 60 min under N2 gas. T3 generated was measured by RIA. T3 generation in the thyroid tissue was dependent on incubation time, amount of the tissue used, concentration of DTT, temperature, and pH. Propylthioracil inhibited T3 formation, while methimazole had no effect. A kinetic study with the homogenate of a thyroid adenoma and 100,000 X g pellet suspensions of two normal and three Graves' thyroids gave apparent Km values of 2.7, 4.9, and 4.1 microM for T4, respectively, and Vmax values of 0.8, 3.0, and 10.9 pmol T3/mg protein.min, respectively. Conversion of T4 to T3 was observed in two of three tumor tissues studied and was markedly enhanced in Graves' thyroid tissues (mean +/- SE, 11.9 +/- 2.0 pmol/mg protein.min) compared to that of normal thyroid tissues (3.2 +/- 0.6 pmol/mg protein.min; P less than 0.01). It is concluded that T4 is enzymatically converted to T3 in normal and Graves' thyroids and differentiated thyroid neoplasms. Moreover, enhanced conversion of T4 to T3 was found in Graves' thyroid tissue.