Clinical effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on various types of neutropenia including cyclic neutropenia

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was investigated for its clinical efficacy in the treatment of various types of neutropenia (3 cases with idiopathic neutropenia of suspected drug induction, 5 cases with idiopathic neutropenia of other origin, and 2 cases with cyclic neutropenia). Treatment with glycosylated rhG-CSF produced in the Chinese Hamster Ovary cells at dose levels of 2–5g/kg/day caused rapid increases of neutrophil counts associated with an improvement of the infection. In cyclic neutropenia patients, marked reduction in the duration of the neutropenic period was observed with rhG-CSF administration started before the period. Intercurrent stomatitis, which occurred in 1 patient, was markedly milder as compared to a previous episode which occurred during an untreated neutropenic period.The treatment of rhG-CSF was well tolerated and no adverse events were observed, nor was there any detectable anti-rhG-CSF antibody in any patients studied; hence the clinical use of rhG-CSF is considered to be safe.These results suggest beneficial effects of rhG-CSF on the recovery of neutrophil counts in cyclic and other types of idiopathic neutropenias, as well as for the treatment of neutropenia-associated infection.     

Synergic effects of kallikrein-kinin and prostaglandins on renin release on infusion of isolated hog kidney with aldosterone

The effects of infusion of a large amount of aldosterone into the renal artery of isolated perfused hog kidney on the release of renin, prostaglandins (PG) and kinin and the excretion of urinary kallikrein were investigated. Infusion of aldosterone at a rate of 100 ng/min (100 to 800 ng/ml of perfusate) resulted in significant releases of renin, PG (PGE₂, 6-0-PGF_1α), and kinin and increase in urinary kallikrein. Infusion of aldosterone and an inhibitor of kallikrein, aprotinin, decreased the releases of renin, PG and kinin and infusion of aldosterone with indomethacin decreased the release of PG but increased that of kinin and urinary kallikrein without significant change in renin releases. These findings suggest that the release of renin by aldosterone may result from synergic effects of renal PG and the kallkrein-kinin system.     

Induction of rapid testicular growth in Japanese quail by phasic electrical stimulation of the hypothalamic photosensitive area

Summary Optic fibers were implanted stereotaxically into the brain of immature male Japanese quail reared under short-day photoperiod (lights on from 1000 to 1800 h), and photosensitive sites in the hypothalamus were examined using gonadal growth and associated hormonal changes as the indices.In the subsequent experiments, bipolar (coaxial) electrodes were implanted chronically using predetermined coordinates for highly photosensitive sites. Henceforth the birds received brief electrical stimulation (square wave, 100 Hz, 100A, 2 min) once daily for 21 consecutive days. When the electrical stimulation was applied early in the dark period, marked gonadal growth was induced, but identical stimulation given in the light period resulted in no testicular growth. The response curve of testicular weight vs clock time of electrical stimulation has a prominent peak at 3 h after the onset of dark. Apparently, the neural complex in the photosensitive area of the quail hypothalamus responds to electrical stimulation as it does to light. We conclude that in photoperiodic birds the principal factor which determines the magnitude of gonadal responses is not the intensity of the stimulus but its timing (circadian phase).Abbreviations GnRH gonadotropin releasing hormone - LD light and dark - LED light emitting diode - CRT cathode ray tube - LH luteinizing hormone - OD outer diameter - ID inner diameter     

Enzyme Aided Regioselective Acylation of Nucleosides

Abstract

Selective protection of the three hydroxyl groups of sugar moiety of nucleosides have been studied by enzyme-catalyzed esterification in organic solvents. Selectively protected products were obtained. The reaction provides an efficient method for selective protection of nucleosides.     

A Facile Preparation of Dehydro-l-ascorbic Acid-methanol Solution and Its Stability

A papain-catalyzed reaction involving the covalent attachment of L-leucine ra-dodecyl ester [Agric. Biol. Chem., 44, 1979 (1980)] was applied to gelatin and succinylated fish protein concentrate. Proteinaceous surfactants formed were found suitable for emulsification of soybean oil. The emulsions prepared with these surfactants were characterized by having a variety of functional properties in terms of hardness, adhesiveness, viscosity and viscoelasticity. Any particular property could be reproduced by intentionally setting the proper conditions for emulsification; for example, the use of a high surfactant concentration resulted in gel formation. The functions of the proteinaceous surfactants were different in many respects from those of Tween-60 and a type of sucrose fatty acid ester used as controls. Several data were added explaining such differences. The feasibility of preparing a mayonnaise-like concentrated emulsion by use of the proteinaceous surfactants is discussed.     

Presence of flagella in Pseudomonas putida is dependent on the ntrA (rpoN) gene

Summary An ntrA (rpoN) mutant of Pseudomonas putida, in which the gene was insertionally inactivated, was constructed. The mutant cells did not have flagella, thus accounting for their poor motility. The mutant phenotype was complemented by introduction of the intact ntrA gene.     

Stage-specific embryonic antigen-4 identifies human dental pulp stem cells

Embryonic stem cell-associated antigens are expressed in a variety of adult stem cells as well as embryonic stem cells. In the present study, we investigated whether stage-specific embryonic antigen (SSEA)-4 can be used to isolate dental pulp (DP) stem cells. DP cells showed plastic adherence, specific surface antigen expression, and multipotent differentiation potential, similar to mesenchymal stem cells (MSC). SSEA-4+ cells were found in cultured DP cells in vitro as well as in DP tissue in vivo. Flow cytometric analysis demonstrated that 45.5% of the DP cells were SSEA-4+. When the DP cells were cultured in the presence of all-trans-retinoic acid, marked downregulation of SSEA-3 and SSEA-4 and the upregulation of SSEA-1 were observed. SSEA-4+ DP cells showed a greater telomere length and a higher growth rate compared to ungated and SSEA-4- cells. A clonal assay demonstrated that 65.5% of the SSEA-4+ DP cells had osteogenic potential, and the SSEA-4+ clonal DP cells showed multilineage differentiation potential toward osteoblasts, chondrocytes, and neurons in vitro. In addition, the SSEA-4+ DP cells had the capacity to form ectopic bone in vivo. Thus, our results suggest that SSEA-4 is a specific cell surface antigen that can be used to identify DP stem cells.     

Discovery and structure-activity relationships of urea derivatives as potent and novel CCR3 antagonists

The synthesis and structure-activity relationships of ureas as CCR3 antagonists are described. Optimization starting with lead compound 2 (IC(50)=190 nM) derived from initial screening hit compound 1 (IC(50)=600 nM) led to the identification of (S)-N-((1R,3S,5S)-8-((6-fluoronaphthalen-2-yl)methyl)-8-azabicyclo[3.2.1]octan-3-yl)-N-(2-nitrophenyl)pyrrolidine-1,2-dicarboxamide 27 (IC(50)=4.9 nM) as a potent CCR3 antagonist.