Atomic step-and-terrace surface of polyimide sheet for advanced polymer substrate engineering.

Typical thermostable and flexible polyimide polymers exhibit many excellent properties such as strong mechanical and chemical resistance. However, in contrast to single-crystal substrates like silicon or sapphire, polymers mostly display disordered and rough surfaces, which may result in instability and degradation of the interfaces between thin films and polymer substrates. As a step toward the development of next-generation polymer substrates, we here report single-atom-layer imprinting onto the polyimide sheets, resulting in an ultrasmooth 0.3 nm high atomic step-and-terrace surface on the polyimides. The ultrasmooth polymer substrates are expected to be applied to the fabrication of nanostructures such as superlattices, nanowires, or quantum dots in nanoscale-controlled electronic devices. We fabricate smooth and atomically stepped indium tin oxide transparent conducting oxide thin films on the imprinted polyimide sheets for future use in organic-based optoelectronic devices processed with nanoscale precision. Furthermore, toward 2D polymer substrate nanoengineering, we demonstrate nanoscale letter writing on the atomic step-and-terrace polyimide surface via atomic force microscopy probe scratching.

Production of three-dimensional tissue-engineered cartilage through mutual fusion of chondrocyte pellets.

In this study, the mutual fusion of chondrocyte pellets was promoted in order to produce large-sized tissue-engineered cartilage with a three-dimensional (3D) shape. Five pellets of human auricular chondrocytes were first prepared, which were then incubated in an agarose mold. After 3 weeks of culture in matrix production-promoting medium under 5.78g/cm(2) compression, the tissue-engineered cartilage showed a sufficient mechanical strength. To confirm the usefulness of these methods, a transplantation experiment was performed using beagles. Tissue-engineered cartilage prepared with 50 pellets of beagle chondrocytes was transplanted subcutaneously into the cell-donor dog for 2 months. The tissue-engineered cartilage of the beagles maintained a rod-like shape, even after harvest. Histology showed fair cartilage regeneration. Furthermore, 20 pellets were made and placed on a beta-tricalcium phosphate prism, and this was then incubated within the agarose mold for 3 weeks. The construct was transplanted into a bone/cartilage defect in the cell-donor beagle. After 2 months, bone and cartilage regeneration was identified on micro-computed tomography and magnetic resonance imaging. This approach involving the fusion of small pellets into a large structure enabled the production of 3D tissue-engineered cartilage that was close to physiological cartilage tissue in property, without conventional polyper scaffolds.

Preoperative internal biliary drainage is superior to external biliary drainage in liver regeneration and function after hepatectomy in obstructive jaundiced rats.

OBJECTIVE: To examine the differences in regeneration rates and functions of the liver at the time of and after hepatectomy in obstructive jaundiced rats with preoperative external and internal biliary drainage. SUMMARY BACKGROUND DATA: The significance of biliary drainage before surgery is controversial in patients with obstructive jaundice. METHODS: After biliary obstruction for 7 days, rats were randomly divided into three groups: obstructive jaundice and hepatectomy (OJ-Hx), external biliary drainage and hepatectomy (ED-Hx), and internal biliary drainage and hepatectomy (ID-Hx). The OJ-Hx group underwent hepatectomy without biliary drainage; the other two groups underwent hepatectomy after biliary drainage for 7 days. At the time of hepatectomy, all rats were provided with internal biliary drainage. On days 0, 1, 2, 3, and 7 after hepatectomy, the DNA synthesis rate and the concentrations of adenine nucleotides and malondialdehyde in the liver were determined as markers of the hepatic regeneration rate, energy status, and lipoperoxide concentration, respectively. Portal endotoxin concentrations were measured and serum hyaluronic acid concentrations were determined as an indicator of hepatic endothelial function. RESULTS: The relative liver weight was significantly higher in the ID-Hx group than in the OJ-Hx group on days 1, 3, and 7 after hepatectomy and than in the ED-Hx group on days 1 and 2. The rate of hepatic DNA synthesis was significantly higher in the ID-Hx group than in the OJ-Hx and ED-Hx groups on day 1. The rate was similar in the ED-Hx and ID-Hx groups on day 2 but was significantly higher than in the OJ-Hx group. The hepatic malondialdehyde concentration was significantly higher on day 1 in the ED-Hx group than in the other two groups. It was lowest in the ID-Hx group throughout the study. Both biliary drainage procedures lowered the portal endotoxin concentration and serum hyaluronic acid concentration at the time of hepatectomy. The serum hyaluronic acid concentration was lowest in the ID Hx group. Hepatic adenine triphosphate concentrations and energy charge levels were similar among the three groups. CONCLUSION: Although both external and internal biliary drainage before hepatectomy improved serum liver function tests, portal endotoxin concentration, and serum hyaluronic acid concentration at the time of surgery, preoperative internal biliary drainage was superior to external drainage, as evidenced by the better liver regeneration and function after hepatectomy.

The combined method: a novel access technique for fetal endoscopic surgery.

BACKGROUND/PURPOSE: To develop practical and less invasive techniques for fetal endoscopic surgery, new methods of lifting the uterine wall to allow fetal surgery without maternal laparotomy were developed and assessed. METHODS: Fetal endoscopic surgical procedures, including tracheostomy and umbilical vascular cannulation, were performed using one of the three methods to enter the uterus without maternal laparotomy in pregnant goats (n = 6; 105 to 115 days' gestation): (1) direct uterine lifting with an air-cushion device; (2) indirect uterine lifting, in which the uterine wall was fixed to the maternal abdominal wall using balloon tip ports inserted percutaneously by Seldinger's method, then the maternal abdomen was lifted mechanically; and (3) combined method, in which low pressure CO2 (5 mm Hg for initial inflation and 2 mm Hg for maintenance) was insufflated into the uterus in addition to the indirect uterine lifting cited above. RESULTS: The direct uterine lifting caused massive injury of myometrium and uterine membranes. The creation of intrauterine space and the protection of the membranes were not accomplished effectively by the indirect uterine lifting only. The combined method provided the adequate intrauterine space and excellent endoscopic visibility for completion of the endoscopic procedures with minimal uterine injury. CONCLUSION: The fetal endoscopic surgery may be accomplished simply and safely by the combined method, a novel technique of uterine lifting to allow fetal surgery without maternal laparotomy.

Cholesterol and bile acid metabolism after selective portal vein ligation.

AIM: To examine the regulatory effect of bile acid level on bile acid synthesis in the liver. METHODS: The portal branch perfusing left lateral and median lobes of the liver was ligated in rats and the activities of hepatic microsomal cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme of bile acid synthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and intrahepatic concentrations of cholesterol and bile acids were determined in the liver lobes deprived of and supplied with portal blood on Days 0, 1, 2, 4, and 7 after selective portal vein ligation (SPVL). RESULTS: In the portal vein (PV)-ligated lobes, liver weight decreased, hepatic cholesterol concentration was unchanged, and microsomal cholesterol concentration increased after SPVL. In the PV-nonligated lobes, liver weight increased, hepatic cholesterol concentration increased, and microsomal cholesterol concentration was unchanged. There were no significant differences in the activities of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase among the PV-ligated and PV-nonligated lobes and the sham-operated controls. Intrahepatic bile acid level increased significantly in the PV-nonligated lobes for 4 days after SPVL, whereas those were essentially constant in the PV-ligated and the sham-operated control liver. Despite significant changes in the concentrations of intrahepatic cholesterol and bile acid, no significant correlations were observed between these concentrations and the activities of cholesterol 7 alpha-hydroxylase. CONCLUSIONS: SPVL causes atrophy and hypertrophy of the PV-ligated and nonligated liver lobes, respectively, without any significant changes in cholesterol and bile acid synthesis. Intrahepatic concentrations of bile acids and cholesterol have no regulatory effect on cholesterol 7 alpha-hydroxylase activity in the SPVL rat model.

Hepatic adenine nucleotides and microsomal cholesterol 7 alpha-hydroxylase activity in the obstructed and freely draining lobes of the liver after selective bile duct obstruction.

BACKGROUND: The effect of selective bile duct obstruction (SBDO) on hepatic reserve function of the bile duct obstructed (BDO) and nonobstructed freely draining (FD) lobes of the liver is obscure. METHODS: The bile duct branches draining from the left lateral and median lobes of the liver were ligated for 4 and 10 days in rats, and hepatic reserve functions in BDO and FD lobes were assessed by microsomal cholesterol 7 alpha-hydroxylase activities and by hepatic adenine nucleotide and energy charge levels. The values were compared with those in sham-operated control liver. Cholesterol 7 alpha-hydroxylase activities were determined by gas-liquid chromatography-mass spectrometry, and hepatic adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels with high-pressure liquid chromatography. RESULTS: The histological examination of the BDO lobes showed proliferation and formation of new bile ductules and fibrous connective tissue linking portal areas. Microsomal cholesterol 7 alpha-hydroxylase activities, hepatic energy charge and adenine nucleotide levels did not differ between FD and BDO lobes, and the values were similar to those in the sham-operated liver. CONCLUSIONS: Selective bile duct obstruction shows no adverse effects on microsomal and mitochondrial functions in either BDO or FD lobes of the liver.

Hepatic adenine nucleotides and microsomal cholesterol 7 alpha-hydroxylase activity in the obstructed and freely draining lobes of the liver after selective bile duct obstruction.

BACKGROUND: The effect of selective bile duct obstruction (SBDO) on hepatic reserve function of the bile duct obstructed (BDO) and nonobstructed freely draining (FD) lobes of the liver is obscure. METHODS: The bile duct branches draining from the left lateral and median lobes of the liver were ligated for 4 and 10 days in rats, and hepatic reserve functions in BDO and FD lobes were assessed by microsomal cholesterol 7 alpha-hydroxylase activities and by hepatic adenine nucleotides and energy charge levels. The values were compared with those in the sham-operated control liver. Cholesterol 7 alpha-hydroxylase activities were determined by gas-liquid chromatography--mass spectrometry, and hepatic adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels with high-pressure liquid chromatography. RESULTS: The histological examination of the BDO lobes showed proliferation and formation of new bile ductules and fibrous connective tissues linking portal areas. Microsomal cholesterol 7 alpha-hydroxylase activities, hepatic energy charge and each adenine nucleotide level did not differ between FD and BDO lobes, and the values were similar to those in the sham-operated liver. CONCLUSIONS: Selective bile duct obstruction shows no adverse effects on microsomal and mitochondrial functions in both the BDO and FD lobes of the liver.

Functional contribution of preoperative portal vein occlusion to hepatectomy. With special reference to hepatic energy charge and DNA synthesis after hepatectomy in rats.

OBJECTIVE: To examine possible functional contributions of preoperative portal branch ligation before hepatectomy (PBL-Hx). DESIGN: Rats were randomly divided into 3 groups. In the PBL-Hx group, the portal branch supplying the left lateral and median lobes of the liver was ligated and the corresponding lobes (48% of the whole liver) were excised 2 days later. In the sham groups (one 68% Hx; the other 47% [hereafter, sham-67% Hx, and sham-47% Hx]), originally ligated lobes and left lateral and caudate lobes, similar to the excised liver volume in the PBL-Hx group, respectively, were excised 2 days after sham operation without PBL. MAIN OUTCOME MEASURES: Hepatic adenine nucleotides and energy charge, which are essential for vital function of hepatocytes, and liver regeneration were assessed by the DNA synthesis rate and weight before Hx and on days 1, 2, 3, and 7 after Hx. RESULTS: The remaining liver weight was restored similarly in the PBL-Hx and sham-47% Hx groups and more rapidly than in the sham-68% Hx group. Further enhancement of DNA synthesis did not occur after Hx in the PBL-Hx group, and hepatic energy charge did not decrease. In contrast, hepatic DNA synthesis was significantly activated depending on the excised liver volume in both the sham-Hx groups and was accompanied by corresponding decreases in hepatic energy charge. CONCLUSION: Preoperative PBL has a functional advantage because the recovery of the remaining liver volume is not impaired and hepatic energy charge is preserved with no further enhancement of DNA synthesis after Hx.

Sequential changes of energy charge, lipoperoxide level, and DNA synthesis rate of the liver following biliary obstruction in rats.

To clarify the effects of obstructive jaundice on the liver, sequential changes of hepatic energy charge, the concentrations of adenine nucleotides and malondialdehyde, DNA synthesis rate, and histology of the liver were examined on the day before and Days 1, 2, 4, 7, and 14 after biliary obstruction in rats and compared with those of sham-operated controls. Foci of necrotic hepatocytes were present on Days 1 and 2 and mitoses of the hepatocytes were frequently observed with a peak on Day 2 in the jaundiced liver. Marked proliferation of bile ductules were subsequently observed on Days 7 and 14, resembling biliary cirrhosis. The DNA synthesis rate was significantly activated after bile duct obstruction with its peak on Day 2, more than nine times higher than the control value and returned to the control level on Day 14. Hepatic ATP concentration and energy charge gradually declined with prolonged jaundice and significantly lower levels persisted after Day 7 compared with the controls. The malondialdehyde level in the jaundiced liver gradually increased and became significantly higher on Day 14. We conclude that obstructive jaundice decreases hepatic energy charge and increases the lipoperoxide level. In the initial stage of obstructive jaundice, the hepatocytes proliferate associated with activated DNA synthesis probably to compensate hepatic damage; however, prolonged obstructive jaundice induces functional hepatic injury possibly necessitating biliary drainage.

Hepatic resection for hepatolithiasis and long-term results.

BACKGROUND: Hepatic resection is an established procedure for treating patients with hepatolithiasis. The long-term results after hepatic resection for hepatolithiasis were appraised. STUDY DESIGN: Of 127 patients with hepatolithiasis seen between 1973 and 1993, 43 patients underwent hepatic resection, and constituted the basis of this study. RESULTS: There was one operative death (operative mortality rate of 2.3 percent) and three deaths as a result of concomitantly associated cholangiocellular carcinoma. Of the remaining 39 patients, the complete stone clearance rate was 67 percent with operation alone, but reached 87 percent when cholangioscopy was used. Operative morbidity was recorded in five patients (12 percent), but they recovered with conservative therapy. Stones recurred in 15 percent of patients after a mean follow-up period of four years (range of three to six years). Eleven (28 percent) of 39 patients died after hepatectomy as a result of related diseases after a mean follow-up of 6.2 years. These 11 patients had associated biliary drainage procedures. They experienced a higher mortality rate (p < 0.05) than patients who did not have biliary drainage. CONCLUSIONS: We conclude that hepatic resection is adequate treatment for hepatolithiasis. The patients having additional biliary drainage procedures had a higher mortality, but one cannot reach conclusions about the negative effect of the drainage procedures because the drainage procedures were done in a selected and not a randomized manner.

Postoperative follow-up of patients with type IVA choledochal cysts after excision of extrahepatic cyst.

BACKGROUND: This study concerns patients who have choledochal cyst with intrahepatic and extrahepatic involvement (type IVA cyst). The extent of excision and the necessity of hepatectomy, including the intrahepatic cyst in these patients have not been clarified. STUDY DESIGN: We have performed excision of the extrahepatic cyst with hepaticojejunostomy upon 13 patients with type IVA cyst during a 16 year period. The present study was done to examine the size of the anastomotic opening by direct cholangiography two weeks postoperatively. The long-term results were assessed to find the appropriate operative management for patients with type IVA cysts. RESULTS: Intrahepatic cysts were present in both hepatic lobes in 11 patients (85 percent). None of the patients had carcinoma after excision of extrahepatic cyst during the follow-up period, which ranged from two months to 16 years. Postoperative late complications occurred in three patients (23 percent), hepatolithiasis in two and cholangitis in one. The anastomotic opening of hepaticojejunostomy was 13.3 +/- 4.5 mm in diameter two weeks postoperatively, which was not significantly different when compared with that in ten patients without late complications (13.4 +/- 4.9 mm). The late complications were successfully treated with either antibiotics or percutaneous transhepatic cholangioscopy, and none required a reoperation. CONCLUSIONS: The results suggest that additional hepatectomy is not required because carcinoma has rarely occurred from the intrahepatic cyst. Excision of an extrahepatic cyst with a wide hepaticojejunostomy is an acceptable operative management for patients with type IVA cysts.

Lumbar artery pseudoaneurysm: an unusual cause of a retroperitoneal hematoma: report of a case.

Pseudoaneurysm of the lumbar artery is a rare complication of penetrating trauma. We present herein a case thought to have been caused by a blow to the left flank without any evidence of a stab wound. In this patient, the diagnosis of a first lumbar artery pseudoaneurysm with a retroperitoneal hematoma was confirmed by computed tomography (CT) findings, after which transcatheter embolization was successfully performed.

Higher serum retinol-binding protein concentration in Indonesian neonates in Surabaya than Japanese neonates in Kobe.

The concentrations of serum retinol-binding protein (RBP), prealbumin (PA) and vitamin A of Indonesian neonates were compared with those of Japanese neonates. The mean serum concentrations of both PA and vitamin A did not differ significantly in Indonesian and Japanese neonates. Indonesian neonates had significantly higher serum RBP (2.75 +/- 0.87 mg/dl, mean +/- SD) than Japanese neonates (1.65 +/- 0.55 mg/dl, p less than 0.01). The molar ratio of vitamin A:RBP in Indonesian infants was significantly lower than in Japanese infants (p less than 0.02), and this in turn is indicative of increased concentrations of retinol-free RBP in the plasma of Indonesian neonates. The results suggest that RBP metabolism in Indonesian neonates differs from that in Japanese neonates.

Characterization of a radioimmunoassay to determine plasma total renin.

The determination of plasma total renin is useful not only as a tool to investigate the physiology of hypertension but also as a marker for Wilms' tumor. A radioimmunoassay (RIA) system to determine plasma total renin was newly developed using monoclonal antibodies specific for both inactive and active renin (inactive + active = total); in this study, an effort was made to confirm that this RIA system truly determines plasma total renin concentrations. First, it was found that this monoclonal antibody stains only the juxtaglomerular apparatus of the kidney. Second, the data determined by the RIA were compared with those obtained by the conventional enzymatic method: samples were activated, and renin activity was assayed by measuring angiotensin I. The coefficient of the data obtained by this RIA system and by the conventional method was 0.921 (p less than 0.01) based on all 89 samples, and 0.809 (p less than 0.01) based on 86 of the 89 samples whose values were less than 600 pg/ml by RIA. As a result of these studies, it was concluded that the newly developed RIA system does determine total renin levels in patients' plasma.

Impairment of superoxide release by alveolar macrophage in rats exposed to oxygen and vitamin E.

We examined the digitonin-stimulated release of superoxide by alveolar macrophages (AMs) from young rats exposed to greater than 95% oxygen for 24-168 h. AMS were obtained by lung lavages, and the release of superoxide stimulated by digitonin was measured by using cytochrome C reduction. The total cell count of lung lavages decreased at 24 and 168 h of oxygen exposure (p less than 0.05 for both). The contamination of polymorphonuclear cells (PMNs) was less than 1% up to 120 h of oxygen exposure, and at 168 h PMNs increased to 5% of total cells in lung lavages. The viability of AMs was greater than 95% up to 72 h and then decreased to 90% at 120 h of oxygen exposure and 87% at 168 h. Digitonin-stimulated superoxide release by AMs recovered from lung lavages in rats exposed to hyperoxia showed a slight increase during the first 48 h. However, oxygen exposure for 72 h or more caused a significant decrease of the stimulated superoxide release of AMs compared to AMs from control rats. This decline in stimulated superoxide release of AMs resulting from hyperoxia was not prevented by vitamin E treatment.

Inhibitory action of bilirubin on superoxide production by polymorphonuclear leukocytes.

To assess the interaction of bilirubin with albumin and to determine the site of bilirubin toxicity in cells, a study was made of the O2- production of neonatal neutrophils (PMNs) by two different stimulators: (1) concanavalin A (Con A) plus cytochalasin D (Cyt D), which acts on the cell surface, and (2) phorbol myristate acetate, which acts intracellularly. PMNs that had been separated from cord blood were incubated for 60 min at 37 degrees C in the solution with different molar ratios of bilirubin/albumin (unbound bilirubin, ranging from 0.35 to 3.92 micrograms/dl). The unbound bilirubin was determined by peroxidase oxidation method. A PMN viability of more than 96% was maintained after the incubation in each of solutions. The O2- production rate of PMNs stimulated by Con A plus Cyt D was inhibited in the presence of unbound bilirubin levels as low as 1.12 micrograms/dl, and the rate decreased as the levels of unbound bilirubin rose. The O2- production rate stimulated by Con A plus Cyt D was more remarkably inhibited than that by phorbol myristate acetate, which directly activates intracellular protein kinase C. These findings suggest that bilirubin toxicity to PMN can be shown at levels of unbound bilirubin as low as those in hyperbilirubinemic sera, and the critical site at which bilirubin exerts its toxicity is mainly in membrane level rather than on intracellular functions.