Effect of pharmacological agents on the activity of the circular and longitudinal smooth muscle layers of human fallopian tube ampullar segments

The in vitro determination of the effects of some pharmacological agents on the outer diameter and axial tension of human Fallopian tube ampullar segments showed that some drugs may act on the circular and longitudinal smooth muscle layers relatively separately. PGF2 alpha elicited an excitatory response in both muscle layers while norepinephrine and isoproterenol decreased the activity. Oxytocin and indomethacin had relatively limited effects on the spontaneous motility of the ampullar segments. The calcium antagonist verapamil inhibited the spontaneous periodic activity.     

Stimulation of phagocytic function by factors inhibiting leukocyte and macrophage migration in humans

Fractions containing macrophage migration inhibition factor (MIF) and leucocyte migration inhibition factor (LIF) were obtained using Sephadex G-200 filtration from supernatant fluids of human lymphocyte cultures stimulated by PHA. The fractions were tested for the ability to affect migration and phagocytic activity of target cells. Peripheral blood leucocyte migration capacity was inhibited by the fraction with the molecular mass of 60,000-70,000 D (LIF), while migration activity of mouse peritoneal exudate cells was suppressed by the fraction with the molecular mass of 20,000-30,000 D (MIF). MIF- and LIF-containing fractions increased almost three-fold Fc-receptor-mediated phagocytic activity of neutrophils.     

The role of surface charge and hydrophilic groups on liposome clearance in vivo.

The effect of negative surface charge and hydrophilic groups on liposome clearance from blood was investigated in mice using liposome-entrapped 67gallium-deferoxamine as a label. The presence of negatively-charged lipids may retard or accelerate liposome clearance. Physicochemical features contributing to optimal retardation of liposome clearance include a hydrophilic carbohydrate moiety and a sterically hindered negatively-charged group. The relevance of the negative charge steric effect is suggested by the finding that phosphatidylinositol phosphate (PIP) and trisialoganglioside (GT1) are less effective than phosphatidylinositol (PI) and monosialoganglioside (GM1), respectively, in retarding liposome clearance. The need for negative charge in addition to the carbohydrate group for optimal effect on retardation of clearance is indicated by the observation that asialoganglioside (AGM1) is less effective than GM1 in this respect. The negative charge effect is observed with liposome bilayers having both low and high temperature phase-transitions. Increasing the molar fraction of negatively-charged lipid (hydrogenated PI derived from soya) from 23 to 41% resulted in a dramatic acceleration of liposome clearance. The clearance-accelerating effect of the high negative charge was specifically directed to the liver with selective reduction of spleen uptake. Increasing liposome size also had an accelerating effect on clearance but in this case it was accompanied by a non-specific concomitant increase of both liver and spleen uptake.     

The imprecision of the ratio of two percentages observed in differential white blood cell counts: a warning

Ratios of two percentages observed in differential counts of leukocytes or lymphocytes are very imprecise if they are based on relatively small numbers of cells. This is shown by the length of the 95% confidence intervals for such ratios. A formula is given for computing the limits of such intervals. They should accompany each observed value for a ratio.     

Assembly of a functional F1 of the proton-translocating ATPase of Escherichia coli

Assembly of the F1 portion of the proton-translocating ATPase of Escherichia coli was examined in vivo. Analysis of strains lacking genes which specify the Fo polypeptides a, b, and c showed that the F1 subunits were able to assemble into a complex in the absence of the Fo subunits. In addition we have investigated the effects of mutations in the individual genes which specify the F1 polypeptides on the assembly process. Mutations of the uncA(alpha), uncG(gamma), or uncD(beta) genes result in a defective assembly of the F1 complex. In contrast, mutations in the uncH(delta) or uncC(epsilon) genes did not prevent assembly of the core alpha beta gamma complex. In these cases, however, the partial F1 complexes were incapable of restoring energy-linked functions to F1-depleted membranes.     

Radiation inactivation target size of rat adipocyte glucose transporters in the plasma membrane and intracellular pools

The in situ assembly states of the glucose transport carrier protein in the plasma membrane and in the intracellular (microsomal) storage pool of rat adipocytes were assessed by studying radiation-induced inactivation of the D-glucose-sensitive cytochalasin B binding activities. High energy radiation inactivated the glucose-sensitive cytochalasin B binding of each of these membrane preparations by reducing the total number of the binding sites without affecting the dissociation constant. The reduction in total number of binding sites was analyzed as a function of radiation dose based on target theory, from which a radiation-sensitive mass (target size) was calculated. When the plasma membranes of insulin-treated adipocytes were used, a target size of approximately 58,000 daltons was obtained. For adipocyte microsomal membranes, we obtained target sizes of approximately 112,000 and 109,000 daltons prior to and after insulin treatment, respectively. In the case of microsomal membranes, however, inactivation data showed anomalously low radiation sensitivities at low radiation doses, which may be interpreted as indicating the presence of a radiation-sensitive inhibitor. These results suggest that the adipocyte glucose transporter occurs as a monomer in the plasma membrane while existing in the intracellular reserve pool either as a homodimer or as a stoichiometric complex with a protein of an approximately equal size.     

Susceptibility of neuroactive peptides to aminopeptidase digestion is related to molecular size.

Peptide fragments derived from the NH₂-terminus of corticotropin were found to exhibit widely differing degrees of stability to degradation by aminopeptidase M. Corticotropin itself was 135 times more stable than its NH₂-terminal pentapeptide, and similar differences in stability were observed with peptides derived from the B-chain of bovine insulin. Enkephalin linked covalently to the A-chain of bovine insulin was at least 100 times more stable than the pentapeptide. The results demonstrate that the molecular size of a peptide is one factor that determines its NH₂-terminal stability.     

Product of extracellular-superoxide dismutase catalysis

Extracellular-superoxide dismutase is a tetrameric enzyme containing four copper atoms. It has previously been shown to catalyse the decay of the superoxide radical, but the resulting product was not determined. In a xanthine oxidase-xanthine system in which about 30% of the electron flux resulted in superoxide radical formation, accumulation of hydrogen peroxide was determined. Catalysis of superoxide radical decay by extracellular-superoxide dismutase was found to result in hydrogen peroxide formation. The catalysed reaction is thus identical to those of previously investigated superoxide dismutases. Human manganese superoxide dismutase was also found to dismute the superoxide radical to hydrogen peroxide and water.