Hepatic conversion of 1-(tetrahydro-2-furanyl)-5-fluorouracil into 5-fluorouracil in patients with hepatocellular carcinoma

The pharmacokinetics of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) and its conversion into 5-fluorouracil (FUra) in liver tissue were studied in ten patients with hepatocellular carcinoma (HCC). The plasma concentration of FT after its intravenous injection (dosage: 800 mg) was computerfitted to a bi-exponential function (C = Ae-alpha t + Be-beta t), indicating a two-compartment disposition. The pharmacokinetic parameters did not significantly differ between the five patients with, and the five without cirrhosis of the liver. The plasma concentrations of FUra likewise showed no significant difference between the two groups. The rates of FT degradation in the liver tissue homogenate were similar for four of the patients with cirrhosis (0.10 +/- 0.05 mumol/g liver protein/30 min) and four of those without it (0.13 +/- 0.05). The rates of cytochrome P-450-dependent FUra formation in the microsomal fraction of liver tissue from two patients (1.1 and 1.3 nmol/mg microsomal protein/30 min) were dramatically reduced to less than half of those of two control subjects (2.4 and 2.7). The estimated rates of FUra formation in the soluble fraction (105,000 X g supernatant fraction) from the two patients (0.1 and 0.13 nmol/mg protein/30 min) were almost identical to those from the controls (0.12 and 0.14), suggesting that the rate in the soluble fraction from HCC patients may not be as strongly affected as the rate in the microsomal fraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clonorchiasis complicated with duodenal papillary cancer in a visitor from China]

It is well known that long-term infection with Clonorchis sinensis often causes bile duct cancer, usually. It occurs in the intrahepatic bile duct. We encountered a rare case of clonorchiasis complicated with duodenal papillary cancer. The patient was a woman from China. Although clonorchiasis is rarely found in Japan, the promotion of international exchange may increase the number of visitors from endemic areas. Thus we must pay sufficient attention to this disease. Also, we reported that the microplate ELISA technique was useful in the diagnosis of clonorchiasis with high accuracy in this case.     

Concomitant mitral valve repair and left ventricular reconstruction in a patient with chronic ischemic mitral regurgitation and inferior left ventricular aneurysm

The surgical approach to ischemic mitral regurgitation with concomitant inferior left ventricular aneurysm remains uncertain in terms of the indication for operation and the short-and long-term outcomes. We performed concomitant mitral valve repair, left ventricular reconstruction, and aortic valve replacement on a 71-year-old male with severe ischemic mitral regurgitation, inferior left ventricular aneurysm, and degenerative aortic regurgitation. Postoperative status was in New York Heart Association functional class I without mitral regurgitation 8 months after operation. We discuss, and review the procedures reported in the literature.     

Change in apoptosis in the gastric surface epithelium and glands after eradication of Helicobacter pylori

BACKGROUND: Change in apoptosis in gastric glands after eradication of Helicobacter pylori has never been reported. AIMS: The purpose of this paper is to investigate the change in apoptosis in gastric glands after eradication of Heliobacter pylori. PATIENTS AND METHODS: We studied 23 Heliobacter pylori-positive patients with duodenal and gastric ulcers, who were monitored for 6-12 months after eradication, and eight controls. Biopsies were taken from the antrum and body. Apoptosis was evaluated immunohistochemically using anti-single stranded DNA antibody. Apoptotic index was calculated by counting immunostained cells in surface epithelial and glandular cells. RESULTS: In the surface epithelium, Apoptotic indexes were significantly higher in patients than in controls. In the upper portion of fundic glands, apoptotic indexes were significantly higher in patients with gastric ulcers (14.2% (9.3, 17.8)) (median (1st quartile, 3rd quartile)) than in controls (8.0% (2.0, 9.0), p < 0.01) and decreased significantly after eradication (3.4% (2.0, 5.3)), p < 0.01). In pyloric glands, apoptotic indexes were no different between patients and controls. In the lower portion of fundic glands, apoptotic indexes were very low, both in patients and in controls. CONCLUSIONS: Our results showed that apoptosis, not only of surface epithelial cells but also of glandular cells in the upper portion of fundic glands, increased in Heliobacter pylori-positive patients with gastric ulcers and decreased to normal levels after eradication of Heliobacter pylori.     

Open heart surgery in a paraplegic patient.

We operated on a patient who had been paraplegic since sustaining a spinal cord injury 11 years ago. We made a reversed L-shaped sternum incision and cannulated all tubes for the cardiopulmonary bypass through a wound window. This provided an excellent surgical view without restricting the patient's upper limbs (needed for wheel chair operation), and recovery was good. Just after surgery, however, it was difficult to control blood pressure and the loss of serum albumin. We believe this is the first report of open-heart surgery undertaken in a paraplegic patient and that the reversed L-shaped incision and careful monitoring of hemodynamics each played an important role in the successful outcome. We hope that this report will help in the treatment of other paraplegic patients who need open-heart surgery.     

Effect of dietary fiber on cytochrome P450IA1 induction in rat colonic mucosa.

The effect of dietary fiber on the induction of cytochrome P450IA1 in rat colonic mucosa after a single intragastric injection of 3-methylcholanthrene (3MC, 20 mg/kg) was investigated by examining the drug-metabolizing enzyme activity, immunoblotting for cytochrome P450IA1 and immunohistochemistry. 7-Ethoxycoumarin-O-deethylase activities were approximately 20-fold higher in microsomes from both proximal and distal portions of the colonic mucosa of control diet-fed 3MC-treated rats compared with those of control diet-fed untreated rats. Strong immunofluorescence for cytochrome P450IA1 was localized in the cytoplasm of the colonic mucosa surface epithelium from the control diet-fed 3MC-treated rats. 7-Ethoxycoumarin-O-deethylase activity and cytochrome P450IA1 content determined by immunoblotting were significantly lower in wheat bran-fed 3MC-treated rats than in control diet-fed 3MC-treated rats. Immunohistochemical analysis showed much weaker immunofluorescence for cytochrome P450IA1 in the surface epithelium of the colonic mucosa of the wheat bran-fed 3MC-treated rats. These observations suggested that dietary fiber can affect the induction of cytochrome P450IA1 in colonic mucosa by dietary inducers or carcinogens.     

Aortic valve replacement with fresh or cryopreserved aortic allograft--initial experience in Japan]

Aortic allograft valves were harvested from non-infected (bacterial or viral) cadavers within 24 hours of death with a family consent, and were sterilized by 4 degrees C antibiotic solution for 48 hours. Then, the allograft was preserved in the 4 degrees C nutrient medium (fresh; TC-199, calf serum and HEPES buffer) or in liquid nitrogen (-196 degrees C) after freezing to -80 degrees C by a programmed freezer. 10% dimethylsulfoxide (DMSO) was used for cryopreservation. Following germ-free confirmation, aortic allograft valves were implanted in 5 patients having aortic regurgitation with good results. Three fresh and two cryopreserved allograft valves were used. Although the follow-up term is very short (maximum 1 year) at the present time, the valve function is quite satisfactory, confirmed by cardiac catheterization and echocardiography. This is the first report in Japan with regard to cryopreservation of allograft valves and clinical use of fresh or cryopreserved valves. We believe that realization and progress of allograft preservation by cryo-technique and establishment of the tissue bank are important for the development of cardiovascular surgery in Japan.     

Contractile effects of bacterial cell walls, their enzymatic digests, and muramyl dipeptides on ileal strips from guinea pigs.

Cell walls isolated from four bacterial species (Streptococcus pyogenes, Lactobacillus plantarum, Streptomyces gardneri, and Nocardia corynebacteriodes), which exhibited the adjuvant effect of stimulating cellular and humoral immune responses against ovalbumin in guinea pigs, caused the slow-starting and long-lasting contraction of guinea pig ileal strips suspended in Tyrode solution. In contrast to these cell walls active in immunoadjuvancy, those isolated from five bacterial species (Micrococcus lysodeikticus, Staphylococcus epidermidis, Arthrobacter atrocyaneus, Corynebacterium insidiosum, and Ampullariella regularis), which lacked immunoadjuvancy at least in intact walls, caused no or very weak contraction of the ileal strips. Further study demonstrated that both a monomer and a polymer of disaccharide-stem peptides, which were obtained by enzymatic degradation of S. epidermis cell wall peptidoglycans, displayed similar contractile effects. It was finally revealed that guinea pig ileum strips showed a definite contractile response to N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and 6-O-stearoyl- and 6-O-(2-tetradecylhexadecanoyl)-MDPs, but not to their analogs, whose C-terminal amino acid was L-isoglutamine or D-isoasparagine in place of D-isoglutamine and which lacked adjuvancy. 6-O-(3-Hydroxy-2-docosylhexacosanoyl)-MDP, on the other hand, caused a slow and lasting relaxation of the ileum strips, but its L-isoglutamine and D-isoasparagine analogs did not.     

Short inverted repeats function as hotspots of intermolecular recombination giving rise to oligomers of deleted plastid DNAs (ptDNAs)

We have determined the nucleotide sequences around the junction points of oligomeric-deleted ptDNAs possessing a head-to-head or tail-to-tail configuration from long-term cultured cell lines and albino plants. It was shown that DNA rearrangement occurred by direct fusion of deleted ptDNAs in an inverted orientation, which was linked by an asymmetrical sequence of 254–698 bp derived from either of the ptDNAs joined. It is notable that inverted repeats of 7–14 bp flank the asymmetrical sequences at each of the junction points. These features of the DNA sequence around the junction points are commonly observed in oligomeric ptDNA with a large-scale deletion regardless of the cell lines employed. It is suggested that the short inverted repeats are involved in the intermolecular recombination of ptDNA. Received: 1 July / 21 October 1996     

Phasically firing neurons in the supraoptic nucleus of the rat hypothalamus: immunocytochemical and electrophysiological studies

Relations between firing patterns and peptides in supraoptic neurons of rat hypothalamic slice preparations were studied by electrophysiology, intracellular fluorescent dye-marking and immunocytochemistry. Seven out of 10 magnocellular neurons which showed phasically firing patterns were identified by injections of Lucifer Yellow-CH (LY); these were also stained with an anti-vasopressin serum. This report presents direct evidence that most of the phasically firing neurosecretory neurons in the supraoptic nucleus contain vasopressin. This study demonstrates the feasibility of combining immunocytochemical and electrophysiological techniques to study the peptides contents of single mammalian neurons.