Enhanced transport of anticancer agents and leukotriene C4 by the human canalicular multispecific organic anion transporter (cMOAT/MRP2).

We established stable human canalicular multispecific organic anion transporter (cMOAT/MRP2) cDNA transfectants, CHO/cMOAT from non-polarized Chinese hamster ovary (CHO)-K1 and LLC/cMOAT from polarized pig kidney epithelial LLC-PK1. Human cMOAT was mainly localized in the plasma membrane of CHO/cMOAT and in the apical membrane of LLC/cMOAT. The ATP-dependent uptake of leukotriene C4 (LTC4) into CHO/cMOAT membrane vesicles was enhanced compared with empty vector transfectants. Km values in CHO/cMOAT membrane vesicles were 0.24 microM for LTC4 and 175 microM for ATP. Drug sensitivity to vincristine and cisplatin in human cMOAT cDNA transfectants decreased, but not to etoposide. Cellular accumulation of vincristine and cisplatin in human cMOAT cDNA transfectants decreased, but not of etoposide. The uptake of LTC4 into CHO/cMOAT membrane vesicles was inhibited by exogenous administration of vincristine or cisplatin, but not that of etoposide. Moreover, this inhibition was more enhanced in the presence of glutathione. These consequences indicate that drug resistance to vincristine or cisplatin appears to be modulated by human cMOAT through transport of the agents, possibly in direct or indirect association with glutathione.

Iron nutrition and anaemia in a malaria-endemic environment: haematological investigation of the Gidra-speaking population in lowland Papua New Guinea.

Blood examination was conducted for the four Gidra-speaking village groups in Papua New Guinea, who were characterized by high Fe intake and high malaria prevalence with marked inter-village differences. The northern riverine villagers, whose Fe intake was higher than the other three village groups, did not suffer from Fe-deficiency anaemia in their malaria-endemic environment; nor did the inland villagers, with their second highest Fe intake and their malaria-free environment, suffer from Fe-deficiency anaemia. However, several individuals of the southern riverine village suffered from anaemia in a malaria-endemic environment, although their Fe intake was almost the same as the inland villagers'. A considerable proportion of the coastal villagers were anaemic, reflecting the lowest Fe intake and the highest malaria prevalence. An inter-village comparison of the relationships between haemoglobin levels and transferrin saturation revealed that the southern riverine villagers needed smaller amounts of circulating Fe for erythropoiesis than the northern riverine and inland villagers, reflecting the long-term human-environment conditions such as the density of malaria vectors and the people's dietary habits. Fe supplementation was not judged effective against hypoferraemia and/or anaemia in such a population. As the incidence of malaria had no significant long-lasting effect on Fe stores or circulating Fe concentration, but did have an effect on anaemia, the hypothesis that malaria causes a transfer of Fe from the blood to parenchymal tissues as a defence against infectious diseases was not supported.

A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation.

By targeting the ATP binding conserved domain in three ATP binding cassette superfamily proteins (P-glycoprotein, multidrug resistance protein, and cystic fibrosis transmembrane regulator), we isolated the cDNA of a new ATP binding cassette superfamily that was specifically enhanced in a cisplatin-resistant human head and neck cancer KB cell line. A human clone homologous to rat canalicular multispecific organic anion transporter (cMOAT) was found and designated human cMOAT. Fluorescence in situ hybridization demonstrated the chromosomal locus of the gene on chromosome 10q24. The human cMOAT cDNA hybridized a 6.5-kb mRNA that was expressed 4- to 6-fold higher by three cisplatin-resistant cell lines derived from various human tumors exhibiting decreased drug accumulation. Human cMOAT may function as a cellular cisplatin transporter.

Therapeutic effects of moxibustion on delayed uterine involution in postpartum dairy cows.

Moxibustion on 12 specific points (Keiketsu in Japanese) was applied for treatment of delayed uterine involution in 16 cows that were diagnosed on the basis of rectal palpation and vaginoscopic examination 21 to 35 days after parturition. The treatment was continued for three consecutive days. Other 32 cows with the delayed uterine involution were either injected intramuscularly with 25 mg PGF2 alpha (17 cows) or infused in utero with 500 mg ampicillin (15 cows). The uterine involution following the treatment was monitored by rectal palpation and vaginoscopic examination. Milk samples were collected three times weekly and used for milk progesterone assay to monitor the ovarian function. No significant difference was observed in the uterine involution among the groups treated with moxibustion, PGF2 alpha or ampicillin. Percentages of cows with abnormal cervical mucus and bacterial isolation from cervical swab decreased remarkably in all groups during 4 weeks after treatment. Forty-six percent of cows with delayed uterine involution was diagnosed as having inactive ovaries. Percentage of cows that responded with ovulation and corpus luteum formation after moxibustion was 67 percent, slightly higher than those in cows treated with PGF2 alpha or ampicillin. Reproductive performance after the moxibustion was well-comparable to those after PGF2 alpha or ampicillin treatment. Result indicates that the moxibustion could be used as the alternative to PGF2 alpha and antibiotics for treating delayed uterine involution in cows.

Cholestatic hepatocellular carcinoma diagnosed by deposits of Lipiodol and treated by combination of endoscopic retrograde biliary drainage and transcatheter arterial embolization.

Cholestatic hepatocellular carcinoma, which grows into the bile duct and causes obstructive jaundice, is rare and difficult to diagnose. A case is presented in which cholestatic hepatocellular carcinoma was detected by deposit of Lipiodol. This is also the first case that was successfully treated by endoscopic retrograde biliary drainage and transcatheter arterial embolization.

Elemental composition of ancient Japanese bones.

Excavated bones (rib) obtained from 50 sites in Japan were measured by ICP atomic emission spectrometry and atomic absorption spectrometry for concentration of 19 elements, including Al, B, Ca, Cd, Cr, Co, Cu, Fe, K, Mg, Mn, Na, Ni, P, Pb, Sr, Ti, V and Zn. One hundred and forty-one specimens were classified into five groups according to Japanese prehistoric and historic eras (Jomon, Yayoi, Kofun, Kamakura and Muromachi, and Edo). The elements, with concentrations which showed no significant change with era were Al, B and Cr. Average concentrations of Ca were in the range 2-2.5 X 10(-1) g g-1 and those of P ranged from 1.1 to 1.3 X 10(-1) g g-1, indicating a well-preserved bone mineral matrix. The Ca/P ratio (mol/mol) was lowest in the Edo group--1.48 as compared with 1.54-1.66 in the other groups. Among the elements which showed changes with era were Pb, Fe, Co and Mn, all of which showed remarkably elevated concentrations in the Edo group. In addition to this unique elemental composition of Edo bones, samples from the Kofun era showed a completely different composition from those of other periods, i.e. they had the highest concentrations of Cd, Zn and Mg, and the lowest concentrations of Cu, K, Ni and Sr. The cause of the elevated Pb concentration in Edo bones is discussed in relation to human activities which may have led to environmental Pb pollution.