Reversal of breast cancer resistance protein (BCRP/ABCG2)-mediated drug resistance by novobiocin, a coumermycin antibiotic.

Breast cancer resistance protein (BCRP/ABCG2) of an ATP-binding cassette half-transporter confers resistance against mitoxantrone and camptothecin derivatives of topotecan and irinotecan. Novobiocin, a coumermycin antibiotic, is known to enhance anticancer drug sensitivity of cancer cells in vitro and in vivo, the mechanism of which remains undetermined. Here we focused on drug efflux pump and examined whether novobiocin reversed drug resistance in multidrug-resistant cells highly expressing BCRP.

Simple non-ion-paired high-performance liquid chromatographic method for simultaneous quantitation of carboxylate and lactone forms of 14 new camptothecin derivatives.

SN-38 (7-ethyl-10-hydroxycamptothecin) is an active metabolite derived from the semi-synthetic compound camptothecin (CPT) named Irinotecan (CPT-11). The antitumor activity of SN-38 is 1000-fold more potent than the parent CPT-11. Fourteen new derivatives of camptothecin have recently been developed by Yakult Honsha (Tokyo, Japan).

Increased TUNEL positive cells in human alcoholic brains.

Alcohol-sensitive neuronal cell loss, which has been reported in the superior frontal cortex and hippocampus, may underlie the pathogenesis of subsequent cognitive deficits. In the present study, we have used the TUNEL labeling to detect the DNA damage in human alcoholic brains. Seven out of eleven alcoholics exhibited TUNEL-positive cells in both superior frontal cortex and hippocampus, which were co-localized with GFAP immunoreactivity.

A functional study on polymorphism of the ATP-binding cassette transporter ABCG2: critical role of arginine-482 in methotrexate transport.

Overexpression of the ATP-binding cassette transporter ABCG2 reportedly causes multidrug resistance, whereas altered drug-resistance profiles and substrate specificity are implicated for certain variant forms of ABCG2. At least three variant forms of ABCG2 have been hitherto documented on the basis of their amino acid moieties (i.e.

Three-dimensional kinetic analysis of side-foot and instep soccer kicks.

Purpose: The purpose of this study was to identify the kinetic aspects of side-foot and instep soccer kicks to understand the different mechanics underlying the two kicks.

Methods: The motions of both kicks were captured using a three-dimensional cinematographic technique. The kicking leg was modeled as a three-link kinetic chain composed of thigh, shank, and foot, from which joint torques and angular velocities were computed.

Carcinosarcoma of the esophagus characterized by myoepithelial and ductal differentiations.

We report a case of carcinosarcoma of the esophagus characterized by ductal and myoepithelial differentiation. A 61-year-old man was operated on for a polypoid tumor of the distal esophagus. Histologically, this tumor was composed of ductal structures and sarcomatous spindle cells surrounding the ducts at the central area of the tumor.

Improvement of skin symptoms and mineral imbalance by drinking deep sea water in patients with atopic eczema/dermatitis syndrome (AEDS).

Deep sea water intake improves skin symptoms and mineral imbalance and decreases serum IgE levels mad IgE-inducing cytokines, IL-4, IL-13 and IL-18 in patients with atopic eczema/dermatitis syndrome (AEDS), while distilled water intake fails to do so.

Molecular and cytogenetic characterization of the mouse ATP-binding cassette transporter Abcg4.

We have cloned a new mouse ATP-binding cassette (ABC) transporter, Abcg4, from a complementary DNA (cDNA) library of mouse brain. The cloned Abcg4 cDNA encodes a protein consisting of 646 amino acids and including one ATP-binding cassette and six transmembrane domains. The Abcg4 protein exhibits high identity (96%) with human ABCG4 in terms of the amino acid sequence.

Metabolism of sulphobromophthalein II. Species differences between rats, guinea-pigs and rabbits.

Interesting species differences in the metabolism of sulphobromophthalein sodium have been observed between rats, guinea-pigs and rabbits. The species difference was measured in terms of sulphobromophthalein monoglutathione conjugate (mGSH) positional isomer formation. After an intravenous injection of sulphobromophthalein to rats, 92% of sulphobromophthalein-mGSH excreted into bile was the alpha-isomer.

Neural cell differentiation from retinal pigment epithelial cells of the newt: an organ culture model for the urodele retinal regeneration.

Transdifferentiation from retinal pigment epithelium (RPE) to neural retina (NR) was studied under a new culture system as an experimental model for newt retinal regeneration. Adult newt RPEs were organ cultured with surrounding connective tissues, such as the choroid and sclera, on a filter membrane. Around day 7 in vitro, lightly pigmented "neuron-like cells" with neuritic processes were found migrating out from the explant onto the filter membrane.

Initial intraorgan formation of mercapturic acid.

The disposition of S-benzyl-glutathione (BSG) in male Wistar rats was evaluated by the HPLC method to examine whether the kidney and liver contributed independently to the biosynthesis of S-benzyl-N-acetylcysteine (BNAc), a mercapturic acid (Chart 1). After intravenous injection, BSG was rapidly transported in both the kidney and the liver at a ratio of about 7:3. Simultaneously, a large amount of BNAc was found in both the kidney and the liver.

Transport of 7-ethyl-10-hydroxycamptothecin (SN-38) by breast cancer resistance protein ABCG2 in human lung cancer cells.

Overexpression of breast cancer resistance protein (BCRP) ABCG2 reportedly confers cancer cell resistance to camptothecin-based anticancer drugs, such as topotecan and 7-ethyl-10-hydroxycamptothecin (SN-38: the active metabolite of irinotecan). We have recently shown that SN-38-selected PC-6/SN2-5H human lung carcinoma cells overexpressed BCRP with the reduced intracellular accumulation of SN-38 and SN-38-glucuronide (S. Kawabata et al.

Effects of high versus low-intensity resistance training on bone mineral density in young males.

The purpose of this study was to investigate the effect of high-intensity and low-intensity resistance training upon bone mineral density (BMD) by comparing the BMD of young male powerlifters (n = 5), recreational trainees (n = 5), and controls (n = 5). Lumbar spine (L2-L4), proximal femur, and whole body BMDs were measured using dual-energy X-ray absorptiometry (DXA). The high-intensity group showed a significantly greater BMD when the whole body and trochanter regions were measured than the low-intensity and control group.

Metabolism of sulphobromophthalein I: positional isomers of sulphobromophthalein monoglutathione conjugate.

Three positional isomers of sulphobromophthalein glutathione monoconjugate (BSP-mGSH) were detected using a paired-ion HPLC method that employs triethylamine phosphate (TEA-H3PO4) as a pairing agent. To confirm that these compounds were glutathione (GSH) conjugates, sulphobromophthalein (BSP) was incubated with a four-fold volume of GSH under alkaline ammonium hydroxide. At least 6 metabolites (3 di-GSH conjugates and 3 isomers of mono-GSH conjugates) were produced under these conditions.

Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells.

Breast cancer resistance protein (BCRP), an ABC half-transporter, is overexpressed in cancer cell lines selected with doxorubicin/verapamil, topotecan, or mitoxantrone. BCRP-overexpressing cells show cross-resistance to camptothecin derivatives such as irinotecan, SN-38 (the active metabolite of irinotecan), and topotecan. To test whether BCRP confers SN-38 resistance, we selected two SN-38 resistant sublines from PC-6 human small-cell lung cancer cells by SN-38, and then characterized these cells.

Induction of MRP1 and gamma-glutamylcysteine synthetase gene expression by interleukin 1beta is mediated by nitric oxide-related signalings in human colorectal cancer cells.

Treatment of human colorectal cancer cells HT29 with interleukin 1beta (IL-1beta) induces expression of the multidrug resistance protein (MRP1) gene encoding the ATP-dependent glutathione S-conjugate export (GS-X) pump and the gamma-glutamylcysteine synthetase (gamma-GCSh) gene encoding heavy (catalytic) subunit of gamma-glutamylcysteine synthetase, the rate-limiting enzyme for the biosynthesis of glutathione (GSH). The induction can be suppressed by N(G)-methyl-L-arginine, a specific inhibitor of nitric oxide synthase (NOS). These results suggest that IL-1beta-mediated MRP1 and gamma-GCSh induction involve nitric oxide (NO) -related signaling.

Invasive bladder cancer after cyclophosphamide administration for nephrotic syndrome--a case report.

We report a case of invasive bladder cancer after cyclophosphamide administration for nephrotic syndrome, and briefly discuss the association of bladder cancer and cyclophosphamide. A 6-year-old boy, who was diagnosed as having nephrotic syndrome, was treated with oral administration of prednisolone and cyclophosphamide for 4 years, receiving a total dose of 49.5 g cyclophosphamide.

Cell death-associated translocation of plasma membrane components induced by CTL.

In the very early stages of target cell apoptosis induced by CTL, we found that fluorescence of labeling probes of the target plasma membrane, such as N-(3-triethylammoniumpropyl)-4-(p-dibutylaminostyryl)pyridin ium dibromide (FM1-43), was translocated into intracellular membrane structures including nuclear envelope and mitochondria. This translocation was associated with the execution of CTL-mediated killing, because neither the CTL-target conjugation alone nor the binding of noncytotoxic Th2 clone with target cell was sufficient to provoke the process. Although FM1-43 translocation was observed in perforin-mediated cytotoxicity, examinations with several other dyes failed to detect the evidence for membrane damages that may cause influx of the dye.

Coreceptor function of mutant human CD4 molecules without affinity to gp120 of human immunodeficiency virus.

Despite extensive mutational studies on the human CD4 molecule and its affinity to human immunodeficiency virus (HIV) envelope glycoprotein gp120, coreceptor functions of such mutant molecules have only been examined by indirect measurement of their affinity to class II major histocompatibility complex (MHC) molecules. In this report, coreceptor functions of mutant human CD4 molecules, which have no or reduced affinity to an HIV envelope protein, gp120, were assessed in a murine T cell receptor/class II MHC recognition system. The substitution of human C" beta strand with the murine homologous segment resulted in the loss of the coreceptor function as well as in the complete loss of gp120 binding capacity, corroborating the consensus that Phe-43 in C" beta strand plays crucial roles in both situations.

Diffusion-weighted echo planar imaging of acute brain infarction: a preliminary report.

The clinical usefulness of diffusion-weighted echo planar imaging (DW-EPI) was studied in 55 patients with acute brain ischemia. Ischemic lesions were identified on DW-EPI as hyperintense regions in all patients before changes were detected by conventional magnetic resonance imaging techniques in 12 cases studied earlier than 6 hours after onset. The earliest case was verified on DW-EPI at 50 minutes after onset.

K(+) channel blockers and cytochrome P450 inhibitors on acetylcholine-induced, endothelium-dependent relaxation in rabbit mesenteric artery.

Acetylcholine caused an endothelium-dependent relaxation in isolated rabbit mesenteric small artery in the presence of nitro L-arginine and indomethacin. The acetylcholine-induced relaxation was attenuated by high K(+) solution, suggesting that the response is mediated by a membrane potential-sensitive mechanism, presumably an endothelium-derived hyperpolarizing factor. The acetylcholine-induced relaxation was also inhibited with tetraethylammonium, 4-aminopyridine and charybdotoxin, but not with Ba(2+), apamin, iberiotoxin nor glibenclamide.

Characteristics of chemiluminescence observed in the horseradish peroxidase-hydrogen peroxide-tyrosine system.

Electrolysis or horseradish peroxidase (HRP)-catalyzed oxidation of tyrosine and bityrosine in aqueous solution at pH 7.4 resulted in light emission in the visible region. Electrolysis of tyrosine emitted light which peaked at 490 nm and was almost completely quenched by superoxide dismutase (SOD), while emission by bityrosine peaked at 530 nm.

Severe impairment of B cell function in lpr/lpr mice expressing transgenic Fas selectively on B cells.

Transgenic lpr/lpr mice expressing functional Fas selectively on B cells were produced in an attempt to elucidate the role of Fas on B cells in the regulation of autoantibody production. The homozygous lpr/lpr mice carrying the transgene did not produce anti-double-stranded DNA antibodies throughout their lives, whereas the development of abnormal lpr T cells (double negative, B220(+)) was not suppressed. Further analyses, however, revealed that the expression of the transgenic Fas on B cells of lpr/lpr homozygous mice resulted in severe impairment of the B cell function.