Action of PGI2 analogs on the pulmonary and systemic circulations in the conscious newborn lamb

Previous work (Lock , J. Pharm. Exp. Ther. :156, 1980) has shown that conventional screening procedures for vasoactive PGI₂ analogs have little value in predicting pulmonary vasodilator activity in the newborn lamb. To gain a better insight into the structural requirements for pulmonary vasoactivity and possibly identify useful compounds for the management of neonatal pulmonary hypertensive disorders, we have tested the following PGI₂ analogs in normoxic and hypoxic newborn lambs: 15(S)-9-deoxy-15-methyl1–9α, 6-nitrilo-PGF₁ (analog I); 9-deoxy-9α, 5-nitrilo-PGF₁ (analog II); (6S, 15S)-15-methyl-PG1₁ (analog III); and (6R, 15S)-15-methyl-PGI₁ (analog IV). A prostaglandin analog mimicking PGI₂ (compound BW245C; (±)-5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl)hydantoin) was tested as well. Compounds were injected into a branch pulmonary artery and any local pulmonary effect could be assessed from the change in the ratio of blood flow to the injected lung over total flow. None of the analogs tested proved to be a selective pulmonary dilator. BW245C was a potent peripheral vasodilator (threshold around 0.5 μg/kg) and indirectly lowered pulmonary vascular resistance through its systemic effects. Analog I also dilated the systemic circulation, but only at the highest dose tested (100 μg/kg). The latter finding is surprising because it was previously shown that the parent, non-methylated compound is a fairly potent and selective pulmonary vasodilator. Analog II and IV were inactive at a dose up to, respectively, 30 and 20 μg/kg. Analog III, on the other hand, weakly constricted the systemic circulation at a dose of 10 μg/kg. These findings suggest that the neonatal pulmonary vasculature is endowed with specific receptor sites which can discriminative between closely related PGI₂ analogs.     

Fc-receptor mediated protein phosphorylation in murine peritoneal macrophages

The effect of Fc receptor engagement on protein phosphorylation in murine peritoneal macrophages has been investigated. Treatment of macrophage cultures with insoluble immune complexes resulted in enhanced phosphorylation of six proteins at 73, 66, 53, 37, 31 and 25 kD. Comparison of the protein phosphorylation patterns induced by immune complexes with those induced by agents which mimic the actions of well known intracellular second messengers (i.e., A23187, dibutyryl cAMP, or phorbol myristate acetate) revealed substantial similarity between Fc receptor induced events and those induced in response to phorbol diesters. There were, however, two phosphorylated proteins which were only seen following stimulation with immune complexes. Thus, more than one kind of protein kinase activity appears to be involved in Fc receptor mediated stimulation of macrophage function.     

Inhibition of parathormone-stimulated bone resorption by type I interferon

The effect of Type I interferon on bone resorption was studied by measuring its effect on parathormone-stimulated calcium release from neonatal murine calvaria in vitro. A pure human recombinant leukocyte interferon hybrid of the A and D subtypes was used, which has high antiviral activity on mouse cells. Calcium release was inhibited in a dose dependent fashion with 50% inhibition at about 10(-10) M or 600 U/ml, and the inhibition was reversible. The presence of interferon was required before or during the activation phase of the resorptive response, when the formation of osteoclasts from precursor cells would occur. When added to actively resorbing bone it had no effect. The data suggest that Type I interferon can inhibit the parathormone-regulated development of active osteoclasts, possibly by inhibiting osteoclast precursor differentiation.     

The rise and fall of surgery for the “floating” kidney

The latter half of the nineteenth century produced a remarkable expansion of surgical practice. Although most of these new techniques and concepts were soundly based, others, such as the movable or floating kidney, were later ridiculed and discredited.In Glasgow Royal Infirmary during the 48 years from 1880, when movable kidney was first mentioned in the annual reports of the hospital, to 1928 472 patients (89% female) were diagnosed as suffering from the condition. Nearly half of them (216) underwent operation and the operative mortality was low. In the first decade of this century an average of 18 cases a year were admitted to the wards of the infirmary. From 1915 to 1920 the number of cases dropped, as did the proportion undergoing operation, but in the 1920s the numbers increased again.In common with other ineffective treatments for imaginary diseases, operations for the movable kidney simply faded away in Britain in the 1930s.     

Measurements of contraction latencies to mechanical and electrical stimulation of the protozoan, Spirostomum ambiguum.

Measurements made on contraction latencies in Spirostomun suggest that mechanical stimulation causes contractions to be initiated by the release of small amounts of calcium from a store tightly coupled to the contractile apparatus. Contraction to electrical stimulation appears to result from the gross electrophoretic mobilization of large amounts of calcium from a loosely coupled store. Contraction latencies to mechanical stimulation were three milliseconds and were independent of stimulus strength, previous stimulation, and contraction probability. For 0.5-millisecond biphasic electrical stimulation the contraction latencies varied widely. Latencies to initial contractions were dependent on stimulus strength: from 1.0 milliseconds for a stimulus that caused a 100% probability of contraction to 2.0 milliseconds for a stimulus that caused a 10% probability of contraction. Latencies of contraction to electrical stimulation were also dependent upon previous stimulation, lengthening to over 300 milliseconds after ten minutes of stimulation. Initial contraction latencies were not affected by previous stimulation to the other (electrical or mechanical) stimulus modality. Repeated electrical stimulation also reduced the animal's resting length and slowed the rate of post contraction re-extension, whereas mechanical stimulation did not have these effects.     

DNA translocation by the restriction enzyme from E. coli K

The restriction endonuclease Eco K binds to a host specificity site and then proceeds to cleave the DNA at sites that may to several thousand bases away. It does this by translocating the DNA past the enzyme in an ATP-dependent reaction that results in the formation of highly twisted loop intermediates. DNA cleavage can occur on either side of the host specificity site.     

A Strain of Rosa damascena Cultured Cells Resistant to Ultraviolet Light

A strain of cultured cells of Rosa damascena Mill. which showed unusual resistance to damage by short wave (254 nanometers) ultraviolet radiation was isolated. The resistant cells were 2.2 to 2.8 times larger and had about twice the amount of DNA and more chromosomes than the parental, sensitive cells. The resistant cells also produced larger quantities of polyphenolic compounds, principally flavonoids, during the later phases of culture growth. At 10 days, resistant cells had 4 times more nonflavonoid polyphenolics and 14 times more flavonoids than parental cells. The resistance, which was also observed only in the later phases of culture growth, was best correlated with the production of polyphenolics, which apparently shielded ultraviolet-sensitive target molecules from damage.