Antibody-directed fibrinolysis. An antibody specific for both fibrin and tissue plasminogen activator

An investigation was made to determine whether it is possible to attract tissue plasminogen activator (tPA) to the site of a thrombus by means of an antibody with affinites for both tPA and fibrin. A bispecific antibody conjugate was constructed by cross-linking two monoclonal antibodies: one specific for tPA, the other specific for fibrin. The bispecific antibody enhanced fibrinolysis by capturing tPA at the site of a fibrin deposit. In an in vitro quantitative fibrinolysis assay, the relative fibrinolytic potency of tPA bound to the bispecific antibody was 13 times greater than that of tPA and 200 times greater than that of urokinase. When fibrin was treated with the bispecific antibody before being mixed with tPA, the relative fibrinolytic potency of tPA was enhanced 14-fold. This capture also occurred when the concentration of tPA present in the assay was less than the concentration of tPA present in normal human plasma. In a human plasma clot assay, samples containing both the bispecific antibody and tPA exhibited significantly more lysis than did samples containing tPA alone. In spite of the increased clot lysis effected by the presence of bispecific antibody, there was no significant increase in fibrinogen or alpha 2-antiplasmin degradation at equal tPA concentrations. The ability of the bispecific antibody to concentrate exogenous tPA in vivo was then examined in the rabbit jugular vein model. Systemic infusion of a small amount of tPA (10,000 units) produced no significant increment in thrombolysis over the level of spontaneous lysis (14 +/- 8%). However, the simultaneous infusion of 10,000 units of tPA and 2 mg of bispecific antibody resulted in 42 +/- 14% (p less than 0.01) lysis. These results suggest that a molecule capable of binding both fibrin and tPA with high affinity could enhance thrombolysis in the circulation by capturing endogenous tPA.     

Codon bias differentiates between the duplicated amylase loci following gene duplication in Drosophila

We examined the pattern of synonymous substitutions in the duplicated Amylase (Amy) genes (called the Amy1- and Amy3-type genes, respectively) in the Drosophila montium species subgroup. The GC content at the third synonymous codon sites of the Amy1-type genes was higher than that of the Amy3-type genes, while the GC content in the 5'-flanking region was the same in both genes. This suggests that the difference in the GC content at third synonymous sites between the duplicated genes is not due to the temporal or regional changes in mutation bias. We inferred the direction of synonymous substitutions along branches of a phylogeny. In most lineages, there were more synonymous substitutions from G/C (G or C) to A/T (A or T) than from A/T to G/C. However, in one lineage leading to the Amy1-type genes, which is immediately after gene duplication but before speciation of the montium species, synonymous substitutions from A/T to G/C were predominant. According to a simple model of synonymous DNA evolution in which major codons are selectively advantageous within each codon family, we estimated the selection intensity for specific lineages in a phylogeny on the basis of inferred patterns of synonymous substitutions. Our result suggested that the difference in GC content at synonymous sites between the two Amy-type genes was due to the change of selection intensity immediately after gene duplication but before speciation of the montium species.     

The hydrology of Lake Victoria

Summary Evidence is presented to show that Lake Victoria is triply stratified the whole year round. The conclusions of FISH (1957) that a uninodal internal seiche operates in the lake is shown to be invalid, and the oscillations of isotherms at E.A.F.R.O. Open Lake Station observed over some years are explained by the day to day wind changes.It is calculated that an internal seiche could operate between the middle and bottom layers, but not between the middle and surface layers, since any such seiche would break down the stratification. Surface waves of the type which normally induce internal seiches are commonly observed on the lake, so it is concluded that the extreme shallowness and great length of Lake Victoria cause a rapid frictional damping of any incipient seiche.Lake Victoria has an annual heat budget of about 9,000 gram/cals/cm². This amount of heat is lost between March and August and regained between August and March. The loss of heat is occasioned mainly by the increase in evaporation from the lake in the period May to October, and partly by an increase in conduction and backradiation. The increase in evaporation rate between May and October assists in disposing of the surplus water derived from the rains in April.The lowest layer in the lake is believed to derive from the inflow of rivers. This layer mixes with the middle layer at the south end of the lake. An apparent area of mixing is suggested north of the Sesse Islands, also.Current measurements indicate a general northward flow of surface water in response to the wind. This is accompanied by a compensating flow of the two lower layers southwards. This latter movement is mainly phasic but probably has a small residual component.Lake level readings from gauges round the lake indicate that the west, north and north-east portions of the lake rise more rapidly in level than the south portion, from April to July.

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Résumé Cette étude montre une stratification permanente du Lac Victoria en trois couches. Elle tend à montrer que la conclusion à l'existence d'une seiche interne uninodale (Fish, 1957) n'est pas valable, et que les oscillations des isotherms observés sont dues au changement du régime des vents d'un jour à l'autre.Le calcul prouve qu'il est possible qu'une seiche interne agisse entre la couche profonde et la couche moyenne, mais certainement pas entre la couche moyenne et la surface, puis-qu' alors elle detruivrait la stratification.Des vagues du type qui normallement provoque les seiches sont couramment observées sur le Lac Victoria. L'Auteur en conclut que la tres faible profondeur et la forme allongée de ce lac causerait un rapide amortissement par friction d'une éventuelle seiche.Le Lac Victoria a un bilan calorifique annuel de 9,000 g/cal/cm². Cette quantité de chaleur est perdue entre mars et août. La perte de chaleur est essentiellement due à l'augmentation d'évaporation de mai à octobre et partiellement à une augmentation de conduction et de radiation. L'accroissement du taux d'évaporation de mai à octobre contribue à eliminer le surplus d eau provenant des précipitations d'avril.Les causes les plus profondes proviendraient de l'apport des rivières. Les couches profondes et moyennes se mêlent a l'extrémité Sud du lac. Il semble aussi que le mélange se fasse au Nord des îles Sesse.Le vent provoque en surface un courant dirigé vers le Nord, compensé par un deplacement vers le Sud des deux couches inférieurs. Ce deplacement est surtout periodique mais à aussi une l égère composante résiduelle.Des relevés de niveau tout autour du lac montrent que d'avril à juillet celui-ci s'élève plus rapidement à l'Ouest, au Nord et au Nord-Est qu'au Sud.