Reduced gastrointestinal toxicity following inhibition of the biliary excretion of irinotecan and its metabolites by probenecid in rats.

Purpose: To ameliorate the late-onset of severe gastrointestinal toxicity provoked by irinotecan (CPT-11), which may be related to the biliary excretion of CPT-11 and/or its metabolites.

Methods: Effects of probenecid, an inhibitor of MRP2/ABCC2, on the biliary excretion and mucosal intestinal tissue concentration of CPT-11 and its metabolites were examined in rats. CPT-11-induced late-onset gastrointestinal toxicity was also evaluated.

Effect of activins AB and B on DNA synthesis stimulated by epidermal growth factor in primary cultured rat hepatocytes.

The effect of activins AB and B on DNA synthesis stimulated by epidermal growth factor (EGF) was studied in primary cultured rat hepatocytes and compared with the effect of activin A, a suppressor of DNA synthesis. Activin AB inhibited DNA synthesis as assessed by [3H]thymidine incorporation. The inhibition by activin AB was detected at 6 ng/ml, and the 12.

Molecular orbital calculation for the model compounds of kainoid amino acids, agonists of excitatory amino acid receptors. Does the kainoid C4-substituent directly interact with the receptors?

Kainoid amino acids are agonists of the AMPA/kainate receptors and exhibit highly potent neuroexcitatory activity. From the results of extensive structure--activity relationship studies, we previously postulated that the C4-substituent of the kainoid amino acids interacts with an allosteric site of the glutamate receptor with electron-donating character. In order to investigate the mode of action in more detail, molecular orbital calculation for model compounds of the kainoid were performed.

Stereoselective pharmacokinetics and pharmacodynamics of disopyramide and its metabolite in rabbits.

The extent to which interactions between enantiomers of disopyramide and between disopyramide and its metabolite, mono-N-dealkylated disopyramide (MND), contribute to stereoselectivity of the anti-arrhythmic effect has been investigated in rabbits by measuring the prolongation of the QUc interval. The plasma unbound fraction of disopyramide enantiomers was constant at a concentration range of 1.44-28.

Heated scallop-shell powder slurry treatment of shredded cabbage.

The main component of scallop-shell powder is calcium carbonate (CaCO3). Through heat treatment, CaCO3 in the shell is converted to CaO, which exhibits antibacterial activity. The disinfecting effect of heated scallop-shell powder on shredded cabbage was investigated for various powder concentrations (0.

Effect of visual display terminal height on the trapezius muscle hardness: quantitative evaluation by a newly developed muscle hardness meter.

The aim of this study was to determine trapezius muscle hardness in 9 healthy volunteers before and after word processing tasks with a video display terminal (VDT) at three different heights. When using a desktop personal computer (PC), no change was observed in muscle hardness even after a 30-min task if a subject was in the reference posture with a declination angle formed by the Reid's line directed toward the upper edge of the PC screen and the horizontal plane within 5-10 degrees. However, an increase in muscle hardness was observed after a 15-min task in a posture of looking up at the screen (angle of elevation: 15-20 degrees) and after a 30-min task in a posture of looking down at the screen (angle of declination: 15-20 degrees).

Effects of supplementation with free radical scavengers on the survival and fertilization rates of mouse cryopreserved oocytes.

Background: This study was conducted to investigate the effects of supplementation with free radical scavengers on the survival and fertilization rates of freeze-thawed mouse oocytes.

Methods: Superovulated oocytes with cumulus cells were cryopreserved by slow freezing in propanediol combined with a rapid thawing protocol. The cryopreservation medium was supplemented with the antioxidant enzymes superoxide dismutase (SOD) and catalase, and with the nitric oxide (NO) scavenger, haemoglobin (Hb).

Possible involvement of ERK 1/2 in UVA-induced melanogenesis in cultured normal human epidermal melanocytes.

UV-induced melanogenesis is a well known physiological response of human skin exposed to solar radiation; however, the signaling molecules involved in the stimulation of melanogenesis in melanocytes following UV exposure remain unclear. In this study we induced melanogenesis in vitro in normal human epidermal melanocytes using a single irradiation with UVA at 1 kJ/m2 and examined the potential involvement of mitogen-activated protein kinases (MAPK) as UVA-responsive signaling molecules in those cells. UVA irradiation did not affect the proliferation of melanocytes, but it did increase tyrosinase mRNA expression, which reached a maximum level 4 hr after UVA irradiation.

Requirement of nitric oxide for murine oocyte maturation, embryo development, and trophoblast outgrowth in vitro.

We investigated the extent to which NO participates in the developmental competence (oocyte maturation, fertilization and embryo development to blastocyst) using an in vitro culture system adding sodium nitroprusside (SNP), NO donor, and NOS inhibitor (N-omega-nitro-L-arginine methyl ester, L-NAME). We also assessed the effects of NO/NOS system on blastocyst implantation using an in vitro trophoblast outgrowth assay. The treatment of low concentrations of SNP (10(-7) M) significantly stimulated meiotic maturation to metaphase II stages in cumulus enclosed oocytes.

Differential activation of ERK 1/2 and JNK in normal human fibroblast-like cells in response to UVC radiation under different oxygen tensions.

The mechanisms by which mitogen-activated protein kinases (MAPK) respond to the input of UV-induced signal transduction pathways and the resulting biological functions are not well understood. We investigated whether the level of oxygen tension of culture was responsible for the differential activation of MAPK and different cellular outcomes in UVC-irradiated cells. The intracellular oxidative level of normal human fibroblast-like cells in a normal atmosphere (normoxic, 20% O2) was increased within 30 min after UVC irradiation.

Upregulation of endogenous heparin-binding EGF-like growth factor and its role as a survival factor in skeletal myotubes.

To investigate the role of heparin-binding EGF-like growth factor (HB-EGF) in skeletal muscle, we studied its function in skeletal myotubes in vitro using mouse C2C12 cells. Expression levels of membrane-anchored HB-EGF (proHB-EGF) protein were increased specifically during their differentiation among epidermal growth factor receptor (EGFR) ligands. Production levels of EGFR on the cell surface were constant.

Low prevalence of clinicopathologic and sialographic changes in salivary glands of men with Sjögren's syndrome.

Sjögren's syndrome (SS) is uncommon in men and there are few reports that describe their clinical features. In the present study, we investigated salivary gland manifestations in men with SS and compared the results with those in women patients. This study included 12 men and 117 women with SS, and the mean stimulated parotid flow rate in men (4.

Abdominal cerebrospinal fluid pseudocyst in a severely handicapped patient with hydrocephalus.

We present a case of an abdominal cerebrospinal fluid pseudocyst as a rare complication of a ventriculoperitoneal shunt. The patient is a severely handicapped bedridden spastic quadriplegic with hydrocephalus. He underwent surgical reconstruction of a shunt tube because of shunt disconnection at the age of 12 years.

The clinical efficacy of low-dose step-up follicle stimulating hormone administration for treatment of unexplained infertility.

The present study was designed to compare the clinical efficacy of low-dose step-up follicle stimulating hormone (FSH) administration with conventional FSH protocol (FSH was injected daily starting with a dose of 150 IU), both combined with intrauterine insemination (IUI), for the treatment of unexplained infertility. A total of 97 unexplained infertility couples was randomly assigned to one or other of the two treatment groups, either conventional FSH with IUI (48 patients) or low-dose step-up FSH with IUI (49 patients), and only the first treatment cycle was evaluated in each protocol. The difference in pregnancy rates per cycle was not statistically significant between the low-dose FSH group and the conventional group [seven of 49 (14.

Requirement of sperm-oocyte plasma membrane fusion for establishment of the plasma membrane block to polyspermy in human pronuclear oocytes.

We investigated whether the incorporation of the sperm membrane into the oolemma contributes to the human plasma membrane block to polyspermy. We used zona pellucida-free oocytes fertilized by intracytoplasmic sperm injection (ICSI) or activated by parthenogenetic activation. Only two of the 35 pronuclear oocytes fertilized by spermatozoa (control) demonstrated one single penetrating spermatozoa.

Syntheses of potent Leu-enkephalin analogs possessing beta-hydroxy-alpha,alpha-disubstituted-alpha-amino acid and their characterization to opioid receptors.

Novel Leu-enkephalin (Leu-Enk) (1) analogs possessing various types of alpha-substituted serine instead of its glycine residue in the position 2 were synthesized via an efficient O,N-migration method. The binding characteristics of the synthetic analogs using Chinese hamster ovary (CHO) cells expressed cloned rat mu-, delta-, and kappa-receptors revealed that [(1R,2S)-Ahh2]Enk (7) was the most potent agonist of delta-opioid receptors among all the synthetic analogs tested, and was 10 times more potent than the native Leu-Enk.

Comparison of hemodynamic changes in two veno-venous bypass techniques modified at the portal cannulation site.

Veno-venous bypass under total vascular exclusion is a useful technique to permit safer resection of hepatic malignancy. We describe here a retrospective study of two modified venous bypass techniques as alternatives to the conventional end-on portal cannulation technique. Portal decompression via inferior mesenteric vein access was performed in eight patients (group A), and portal decompression via a passive shunt between a branch of the mesenteric vein and the right saphenous vein was performed in a second group (group B; n = 8).

Hyperthermo-chemo-hypoxic isolated liver perfusion for hepatic metastases: a possible adjuvant approach.

As a possible intraoperative adjuvant approach to treating hepatic metastases we developed a method of hyperthermo-chemo-hypoxic isolated liver perfusion in combination with hepatic resection. This method was applied to 11 patients with colorectal hepatic metastases between 1992 and 1995. One patient died on postoperative day 14 of hepatic failure (9% mortality), the cause of which was live temperature that reached 42.

Development of a portable multipurpose recorder using a 24-hour ambulatory recorder: application to polysomnography.

With the advance of chronobiology, demands for simultaneous long-term monitoring and recording of various biosignals are increasing. To meet these demands we have developed a portable multipurpose recording system using a 24-hour ambulatory recorder. This technical achievement of less restrictive round-the-clock simultaneous recording of biosignals from not only the circulatory system, but also from the neurological and digestive systems of a subject in his/her daily life will contribute to clinical research on circadian variations of biosignals and EEG analysis during sleep.

A novel brain-derived member of the epidermal growth factor family that interacts with ErbB3 and ErbB4.

A novel member of the epidermal growth factor (EGF) family, the neural- and thymus-derived activator for ErbB kinases (NTAK), has been purified and cloned. Five alternative spliced isoforms have been detected in the rat adrenal pheochromocytoma cell line, PC-12 cells. The rat NTAK alpha2a isoform exhibits 94% identity in its primary sequence with the human NTAK alpha isoform.

Predominant role of local immunosuppressive effect in enhanced efficacy of liposomal FK506 in organ transplantation.

Liposomal FK506 is a new formulation of FK506 that increases FK506 levels in the liver and decreases them in the kidney in comparison to conventional IV formulation. In the present study, the efficacy of liposomal FK506 was evaluated in canine kidney and liver transplantation models. Liposomal FK506 increased the immunosuppressive efficacy of FK506 in the liver transplantation model, but decreased it in the kidney transplantation model.