Effects of 16,16-Dimethyl-trans-delta 2-PGE1 methyl ester (ONO-802) on uterine, placental and ovarian circulation (author's transl)

Doses of the drugs which produce uterine contraction were given intravenously to various species of animals. Placental and ovarian circulations were measured by the thermocouple method and/or microangiography. Uterine arterial blood flow (UABF) was measured by the electromagnetic flowmeter. Both placental blood flow (PBF) and UABF decreased with the administration of ONO-802, PGE1 or PGF2 alpha to to rabbits and dogs. Oxytocin and noradrenaline also decreased PBF in rabbits. ONO-802 or PGE1 lowered arterial blood pressure (BP) in rats, rabbits and dogs. PGE2 alpha elevated BP in rats and dogs and lowered it in rabbits. Oxytocin produced no changes in PB while noradrenaline elevated BP in rabbits. Ovarian blood flow in pregnant rabbits was reduced by ONO-802, PGE1 or PGF2 alpha. Little influence was seen with oxytocin. Regarding the luteal microvasculature in pregnant rats, ONO-802, PGF2 alpha and noradrenaline exhibited vasoconstricting effects. PGF2 alpha induced abortion and decreased plasma progesterone levels. These results suggest that the inhibitory effects of ONO-802 on the uterine and placental circulation are strongly influenced by the uterine contractile effect and that the inhibitory effect on the ovarian circulation in rats is one of pharmacological effects not concerned with the abortifacient or luteolytic effect.     

Specific hybrid liposomes composed of phosphatidylcholine and polyoxyethylenealkyl ether with markedly enhanced inhibitory effects on the growth of tumor cells in vitro

The hybrid liposomes (90mol% DMPC/10mol% C12(EO)8 and 90mol% DMPC/10mol% C12(EO)12) have a highly inhibitory action against the growth of tumor cells. The uniform and stable structure of the hybrid liposomes was revealed on the basis of electron microscopy and dynamic light scattering measurements.     

Dynamics and organization of MAP kinase signal pathways

In the budding yeast, Saccharomyces cerevisiae, four separate but structurally related mitogen-activated protein kinase (MAPK) activation pathways are known. The best understood of these regulates mating. Pheromone binding to receptor informs cells of the proximity of a mating partner and induces differentiation to a mating competent state. The MAPK activation cascade mediating this signal is made up of Ste11 (a MEK kinase [MEKK]), Ste7 (a MAPK/ERK kinase [MEK]), and the redundant MAPK-related Fus3 and Kss1 enzymes. Another MAPK activation pathway is important for cell integrity and regulates cell wall construction. This cascade consists of Bck1 (a MEKK), the redundant Mkk1 and Mkk2 enzymes (MEKs), and Mpk1 (a MAPK). We exploited these two pathways to learn about the coordination and signal transmission fidelity of MAPK activation cascades. Two lines of evidence suggest that the activities of the mating and cell integrity pathways are coordinated during mating differentiation. First, cells deficient in Mpk1 are susceptible to lysis when they make a mating projection in response to pheromone. Second, Mpk1 activation during pheromone induction coincides with projection formation. The mechanism underlying this coordination is still unknown to us. Our working model is that projection formation generates a mobile second messenger for activation of the cell integrity pathway. Analysis of a STE7 mutation gave us some unanticipated but important insights into parameters important for fidelity of signal transmission. The Ste7 variant has a serine to proline substitution at position 368. Ste7-P368 has higher basal activity than the wild-type enzyme but still requires Ste11 for its function. Additionally, the proline substitution enables the variant to transmit the signal from mammalian Raf expressed in yeast. This novel activity suggests that Ste7-P368 is inherently more permissive than Ste7 in its interactions with MEKKs. Yet, Ste7-P368 cross function in the cell integrity pathway occurs only when it is highly overproduced or when Ste5 is missing. This behavior suggests that Ste5, which has been proposed to be a tether for the kinases in the mating pathway, contributes to Ste7 specificity and fidelity of signal transmission.     

A nation-wide surveillance of pathogen in elderly patients with urinary tract infections. 2nd Report: Sensitivities of pathogen for oral antibacterial agents

A nation-wide surveillance of sensitivities of bacteria, which were isolated from elderly patients with UTIs aged more than 65 in 190 private clinics and 73 hospitals, for oral antibacterials, CPFX, OFLX, NFLX, CPDX and CCL, was conducted in August and September in 1993. Antibacterial activities of 5 agents against all 1,511 strains were intensified in CPFX, OFLX, NFLX, CPDX and CCL in that order. Major pathogens such as Enterobacteriaceae, E. faecalis, Staphylococcus spp. and P. aeruginosa were more susceptible to fluoroquinolones than cephems. The rate of resistant strains to antibacterials was higher in isolates from older patients, patients with complicated UTIs and with indwelling catheter. The representative of resistant strains was P. aeruginosa, and about 50% of the strains of P. aeruginosa were resistant to even CPFX which had the most superior antibacterial activity among the 5 agents. About 40% of the S. aureus were MRSA, which were almost resistant to the 5 agents. From the above findings, it was confirmed that a high recovery rate of strains which is less susceptible to various antibacterials is one of the refractory factors in elderly patients with UTIs, particularly in complicated UTIs and with indwelling catheter. Regardless of the size of the clinic or hospital, Fluoroquinolones are more suitable for the treatment of elderly patients with UTIs than cephems.     

Spontaneous renal cell tumors in Long-Evans Cinnamon rats

Neoplastic lesions of the kidneys in untreated Long-Evans Cinnamon (LEC) rats of 57-118 weeks old (85 males and 34 females) and male F344 rats of 64-93 weeks old (59 males) were examined histologically. The incidences of renal cell tumors in male and female LEC rats were 6/80 (8%) in weeks 57-65, 3/19 (16%) in weeks 66-75, 3/8 (38%) in weeks 76-105 and 7/12 (58%) in weeks 106-118. Of these tumors, 13 were microscopic adenomas and 7 were renal cell carcinomas. The copper content of the kidneys was about three times higher in LEC rats than in F344 rats (P < 0.001), but the iron content of the kidneys was similar in the two strains.     

Alteration of T-lymphocyte subpopulations in patients with primary renal diseases and systemic lupus erythematosus

Forty-eight patients with a variety of primary renal diseases and systemic lupus erythematosus (SLE) were examined for the proportion of circulating T lymphocytes bearing receptors for IgM (T mu cells) or IgG (T gamma cells). Although the control group showed strikingly similar mean values for both T mu and T gamma cells, the whole group of patients with primary renal diseases and SLE showed a wide scatter of values. Sixteen patients with primary renal diseases and SLE had higher proportions of T gamma cells than the control group, whereas seven patients with chronic glomerulonephritis (CGN), membranoproliferative glomerulonephritis (MPGN), lipoid nephrosis (LN), and SLE showed very marked decrease in the proportions of T gamma cells in the peripheral blood. On the other hand, six out of the total group of patients had low proportions of T mu cells in the peripheral blood. However, no consistent relationship between the proportion of T mu and T gamma cells was found in our study. These findings indicate that there exists a heterogeneity of T-lymphocyte subpopulation distribution in some patients with primary renal diseases and SLE. The possible significance of these phenomena in the pathophysiology of renal diseases is discussed.     

Determination of horseradish peroxidase concentration using the chemiluminescence of Cypridina luciferin analogue, 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin-3-one

The chemiluminescence of the Cypridina luciferin analogue, 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin++ +-3-one (MCLA) was observed at 462 nm in the presence of horseradish peroxidase (HRP) and the total spectrum of light emitted was found to depend linearly on HRP concentration. Methods for the determination of HRP concentration using the chemiluminescence was investigated. HRP could be detected in the range from 100 pmol/L to 100 nmol/L under the optimum condition, H2O2 (10 mmol/L) and MCLA (10 mumol/L) at pH 5.8.