Preliminary clinical experience with the antiarrhythmic effect of PGF2a

A total dosage up to 1 mg PGF_2a as i.v. infusions of 10–40 μg/min. was investigated on patients with arrhythmias of several kinds. We found therapeutic effects in 5 of 6 patients with constant extrasystoles and in one patient with digitalis - induced partial AV-block respectively. In 3 of 4 patients with acute tachyarrhythmias the results were not convincing, probably due to a dosage not high enough. An increase of the diastolic stimulation threshold usually seen with other antiarrhythmics was not to be observed in 3 patients. The mechanism of action of PGF_2a has not yet been clarified.     

Isolation of mutants of the obligate methanotroph Methylomonas albus defective in growth on methane

A strain of Methylomonas albus BG8WM, a type 1 obligate methanotroph, which had been maintained for 2 ycars by serial passage on solid medium containing methanol as a carbon source was found to mutate at a frequency of 10^-5-10^-6 to resistance to dichloromethane (DCM^R), the parental strain BG8 did not give rise to DCM^R colonies. DCM^R strains were no longer capable of growth on methane as a carbon cource and exhibited greatly reduced or undetectable methane mono-oxygenase activity. The mutants fell into three groups on the basis of SDS-PAGE analysis of the polypeptide profiles of the particulate fraction of cell extracts. One or more of four polypeptides of Mr 70,000, 50,000, 25,000 and 23,000 were implicated as being components of the methane mono-oxygenase. Spontaneous reversion to growth on methane and sensitivity to dichloromethane occurred at a frequency of about 10^-8. The loss of methane mono-oxygenase activity was not associated with loss of the resident 55 kb plasmid.Abbreviations DCM^R dichloromethane-resistant - SDS-PAGE sodium dodecyl sulphate polyacrylamide gel electrophoresis - NMS nitrate minimal salts medium     

ASP-56, a new actin sequestering protein from pig platelets with homology to CAP, an adenylate cyclase-associated protein from yeast.

A new 56 kDa actin-binding protein (ASP-56) was isolated from pig platelet lysate. In falling ball viscosimetry it caused a reduction in viscosity that could be attributed to a decrease in the concentration of polymeric actin. Fluorescence measurements with NBD-labelled actin showed reduction of polymeric actin, too. These results could be explained by sequestering of actin in a non-polymerizable 1:1 ASP-56/actin complex. Sequencing of about 20 tryptic peptides of ASP-56 and comparison with known sequences revealed about 60% homology to the adenylate cyclase-associated protein (CAP) from yeast.     

ARAGONITE CRYSTALS IN SPIROGYRA SP. (CHLOROPHYTA)

Intracellular crystals of aragonite have been identified by selected area electron diffraction (SAED) in a species of the freshwater filamentous alga Spirogyra from the Thames River, Ontario, Canada. The crystals are 2 to 24 μm in diameter, and characterized by a unique cross-shaped morphology, in which needle-like, or prismatic outgrowths develop from a common axis. Crystals may be dispersed throughout filaments, but tend to cluster as aggregates towards the centre .     

Effect of continuous infusion of a low dose of GnRH antagonist on serum LH and testosterone concentrations, spermatogenesis and semen quality in the rhesus monkey (Macaca mulatta)

Treatment of 4 adult male rhesus monkeys for 8-12 months with 100-400 micrograms of a GnRH antagonist/day by means of using osmotic minipumps led to suppressed serum concentrations of LH and testosterone followed by various degrees of recovery toward pretreatment values. The serum LH response to a challenge of native GnRH was reduced by 30-75% during antagonist treatment. The serum testosterone response to GnRH was exaggerated above the response in the pretreatment period, suggesting hypersensitivity of the testis to gonadotrophin. Antagonist administration under these conditions did not alter body weight or abolish ejaculatory response. Antagonist infusion caused a 96% decrease in sperm counts. Spermatozoa recovered during the final month of antagonist treatment showed a reduced ability to penetrate denuded hamster ova. Testicular biopsies performed at the end of antagonist treatment revealed persistent spermatogenesis. However, the cellularity of the seminiferous tubules was decreased below that of pretreatment biopsies. The results of this study suggest that the amount of testosterone needed to maintain normal spermatogenesis is greater than that needed to maintain electroejaculatory response in monkeys.     

Cytotoxic T lymphocytes from mice with soluble class I Q10 molecules in their serum are not tolerant to membrane-bound Q10

Q10 is a class I Qa-2 region-encoded molecule that is secreted by the liver and present in serum at high concentrations (about 10 to 60 micrograms/ml) in most strains of mice. The amino terminal portion of this molecule can also be expressed as an integral membrane protein by splicing the 5' end of the Q10 gene to the 3' end of H-2Ld and transfecting the hybrid gene into murine L cells. Because CTL primarily recognize polymorphic determinants controlled by the alpha 1 and alpha 2 domains of class I molecules and because the Q10d/Ld product expressed by transfected L cells includes the alpha 1 and alpha 2 domains of Q10d, we could address whether mice bearing serum Q10 were tolerant to this molecule at the CTL level. The results of these experiments demonstrate that Q10+ mice are able to generate H-2-unrestricted CTL activity against Q10d expressed on transfected L cells, and this response was not inhibitable by the addition of Q10-containing normal mouse serum. It is unlikely that this CTL activity is due to possible polymorphic differences in Q10 alleles, since semisyngeneic BALB/c (H-2d) mice, from which the Q10d hybrid gene construct was derived, are able to generate anti-Q10d effector cells. The Q10d molecule was shown to cross-react with H-2Ld, lending support to the concept that Qa genes can serve as donors for polymorphic sequences found in H-2K, -D, and -L. That mice can generate anti-Q10 CTL activity suggests that this soluble class I protein does not act as a toleragen for these cells. The implications of these findings for an understanding of self-tolerance are discussed.