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A Runge

Publications and source records attributed to A Runge.

17 recordsLinked to original sources
PubMed2001

Functional synergy between Rab5 effector Rabaptin-5 and exchange factor Rabex-5 when physically associated in a complex.

Rab GTPases are central elements of the vesicular transport machinery. An emerging view is that downstream effectors of these GTPases are multiprotein complexes that include nucleotide exchange factors to ensure coupling between GTPase activation and effector function. We have previously shown that Rab5, which regulates various steps of transport along the early endocytic pathway, is activated by a complex consisting of Rabex-5, a Rab5 nucleotide exchange factor, and the effector Rabaptin-5. We postulated that the physical association of these two proteins is necessary for their activity in Rab5-dependent endocytic membrane transport. To evaluate the functional implications of such complex formation, we have reconstituted it with the use of recombinant proteins and characterized its properties. First, we show that Rabaptin-5 increases the exchange activity of Rabex-5 on Rab5. Second, Rab5-dependent recruitment of Rabaptin-5 to early endosomes is completely dependent on its physical association with Rabex-5. Third, complex formation between Rabaptin-5 and Rabex-5 is essential for early endosome homotypic fusion. These results reveal a functional synergy between Rabaptin-5 and Rabex-5 in the complex and have implications for the function of analogous complexes for Rab and Rho GTPases.

Animals↗
PubMed1996

Population genetic studies of HLA-G: allele frequencies and linkage disequilibrium with HLA-A1.

HLA-G is a class I gene that is expressed in the extravillous cytotrophoblast. Although the function of this gene is still unknown, its expression at the maternal-fetal interface suggests that HLA-G may play a key role in the induction of tolerance during pregnancy. Preliminary to our studies of the effects of HLA-G polymorphisms on pregnancy outcome, we have defined HLA-G alleles in the Hutterites. We report here the presence of nine HLA-G alleles that differ with respect to nucleotide sequences, including four groups of alleles that differ with respect to amino acid sequences, and striking linkage disequilibrium between HLA-G and HLA-A alleles. The levels and sites of polymorphism in HLA-G suggest that this gene had a unique evolutionary history and may perform nonclassical functions at the maternal-fetal interface.

Adult↗
PubMed1992

Nitric oxide and prostacyclin inhibit fetal platelet aggregation: a response similar to that observed in adults.

OBJECTIVE: We evaluated the relative importance of two endothelium-derived substances, prostacyclin and nitric oxide, in their ability to inhibit aggregation of fetal and maternal platelets. STUDY DESIGN: The effects of various concentrations of prostacyclin and S-nitroso-N-acetylpenicillamine (which releases nitric oxide) on platelet aggregation were studied by means of platelet-rich plasma from at least five to six subjects per group. Fetal blood was collected from umbilical vein at delivery. Maternal venous blood was collected within 4 hours of delivery. Platelet aggregation was monitored with a platelet aggregation profiler. Adenosine diphosphate was used as the aggregating agent. Statistical differences between means were evaluated with two-way analysis of variance or Student t test. RESULTS: Prostacyclin and S-nitroso-N-acetylpenicillamine inhibited aggregation of fetal and maternal platelets, but prostacyclin was more potent. Fetal platelets were more sensitive than maternal platelets to prostacyclin and S-nitroso-N-acetylpenicillamine. CONCLUSION: Prostacyclin appears to be more important in preventing aggregation of platelets in the feto placental circulation.

Adenosine Diphosphate↗
PubMed1989

Simultaneous lupus anticoagulant and anticardiolipin assays and clinical detection of antiphospholipids.

Lupus anticoagulants and/or anticardiolipin antibodies were detected in 100 patients with autoimmune disorders, thrombosis, or pregnancy loss. Significant agreement between tests for these two antiphospholipid activities was lacking. Performing both assays is thus important in maximizing the likelihood of detecting antiphospholipids that may have clinical relevance.

Abortion, Spontaneous↗
PubMed1986

Lupus anticoagulants: improved diagnosis with a kaolin clotting time using rabbit brain phospholipid in standard and high concentrations.

We utilized a kaolin-activated partial thromboplastin time (APTT) using rabbit brain phospholipid, in which the capacity of a fourfold increased "high" phospholipid concentration (PC) to normalize the abnormal "standard" PC-APTT in patients with lupus anticoagulants is assessed. This system was also used to measure factors VIIIC, IX, and XI. The tissue thromboplastin inhibition test (TTI), a prothrombin time system in which the activity of a lupus anticoagulant is unmasked by the use of dilute thromboplastin, was simultaneously evaluated. Test sensitivity was defined by results on 31 consecutive patients with standard PC-APTT inhibitors and no bleeding tendency. Specificity was based on 94 patients with various other coagulopathies, including coagulation factor inhibitors, severe congenital factor deficiencies, hepatic insufficiency, and warfarin and heparin treatment. Twenty-one patients with lupus erythematosus and standard PC-APTT results within normal limits were also tested. Sensitivity of the APTT system was superior to that of the TTI (97% v 58%); high PC normalized clotting time ratios and factor levels. Positive results were common with both assays in the group of 20 heparinized patients. The APTT system had superior specificity in remaining cases; there were no positive tests among 74 patients. The lupus erythematosus group had a significant decrease in the clotting time ratio with high PC, indicating that low-level lupus anticoagulants are quite prevalent in this group. The kaolin clotting time using rabbit brain phospholipid in standard and high concentrations is a simple, sensitive, and specific technique for diagnosis of lupus anticoagulants.

Animals↗
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