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H J Reimers

Publications and source records attributed to H J Reimers.

At least 19 recordsLinked to original sources
PubMed1979

Disassembly of microtubules in the Lesch-Nyhan Syndrome? (Lesch-Nyhan syndrome and microtubules).

The Lesch-Nyhan syndrome is an unusual disease. It combines neurological disorders, behavioural disturbances, metabolic changes and haematological symptoms. The syndrome is caused by an X-chromosomal transmitted enzyme deficiency of the 'salvage pathway' in purine metabolism. The hitherto unexplained pathogenesis was the reason for investigations into metabolism and morphology of the blood cells of a patient suffering from the syndrome. Along with the defect in guanine nucleotide resynthesis there was a defect of microtubules in platelets and a sphaerocytosis in red cells, which could be the result of a disassembly of structural proteins. The development and maintenance of the highly heteromorphic structure of nerve cells and the neuronal function including axonal transport of cell organelles and transmitters is dependent on microtubules. Thus a disassembly of microtubules could be the mechanism in the pathogenesis of this complex syndrome.

Adenine Phosphoribosyltransferase↗
PubMed1977

Properties of washed human platelets.

We have shown previously that washed human platelets resuspended in Tyrode solution containing albumin and apyrase maintain their disc shape and their ability to aggregate upon the addition of low concentration of ADP, providing fibrinogen is added to the suspending medium. We have now examined their responses to other aggregating and release-inducing agents. Collagen, arachidonate, thrombin, immune serum globulin, the ionophore A23, 187 and phytohaemagglutinin from Phaseolus vulgaris caused aggregation and release of granule contents. The response to adrenaline was variable. Serotonin caused the platelets to change shape but no aggregation or release occurred. Addition of a small amount of plasma was necessary for ristocetin-induced aggregation. Polylysine caused immediate platelet-to-platelet adherence with little or no release of granule contents. Responses to collagen or thrombin were greater in a modified medium containing magnesium but no calcium; in this medium, aggregation caused by ADP or polylysine was followed by the release of granule contents whereas these agents caused aggregation without release in a medium with both calcium and magnesium. When protein was omitted from the suspending medium, platelet aggregation in response to ADP was variable. In this medium, collagen and thrombin caused more extensive release than in the albumin-containing medium. Aggregation by polylysine was accompanied by release and extensive lysis in the protein-free medium. Thus, the composition of the final resuspending medium has a major effect on the responses of washed human platelets to aggregating agents.

Arachidonic Acids↗
PubMed1977

Labeling of the releasable adenine nucleotides of washed human platelets.

In rabbit platelets, the metabolically active ATP pool equilibrates with the releasable ATP pool within 1 day. The studies showing this have now been extended to human platelets. Human platelets labeled with 14C-adenosine or 14C-adenine were incubated for up to 10 hr in vitro at 37 degrees C. After 10 hr, about 12% of the total platelet 14C-ATP and 14C-ADP had become releasable with thrombin (4.2 units/ml). Lysis of platelets did not occur, since less than 1% of the platelet-bound 51Cr from platelets labeled with this radioisotope appeared in the ambient fluid upon thrombin treatment. The 14C-ATP/14C-ADP ratio of the released adenine nucleotides (7.6) was similar to the 14C-ATP/14C-ADP ratio of the nonreleasable adenine nucleotides (7.1) 2 hr after the labeling with 14C-adenosine. However, upon prolonged incubation (10 hr) in vitro, the 14C-ATP/14C-ADP ratio of the releasable adenine nucleotides decreased to 2.7. The adenylate energy charge and the 14C-ATP/14C-ADP ratio of the metabolic adenine nucleotide pool did not change significantly during the time of observation. The 14C-ATP content of the platelets decreased by less than 1% hr of incubation at 37 degrees C. These observations are interpreted to mean that the 14C is transferred from the metabolically active, nonreleasable adenine nucleotide pool of human platelets into the releasable adenine nucleotide pool as ATP and is partially hydrolyzed there to yield ADP. The transfer of ATP across the storage organelle membrane of platelets may be similar to transport processes in the chromaffin cells of the adrenal medulla and may represent a general phenomenon in cells that possess storage organelles containing adenine nucleotides.

Adenosine Diphosphate↗
PubMed1976

In vitro and in vivo functions of thrombin-treated platelets.

Thrombin-induced platelet aggregation has been generally believed to be irreversible. However, thrombin-induced aggregation of washed platelets is reversible if fibrin formation is prevented or the fibrin which binds the platelets together is removed from the platelet aggregates. After treatment with high concentrations of thrombin (0.5 units/ml) single platelets can be recovered that have lost practically all of their releasable serotonin and adenine nucleotides. These platelets are able to aggregate upon addition of low concentrations of ADP in the presence of fibrinogen. They aggregate in response to the ionophore A23, 187 in the absence of added fibrinogen, whereas sodium arachidonate-induced aggregation requires added fibrinogen. Thrombin-treated platelets change their shape in response to collagen in the absence of fibrinogen, and will aggregate upon the addition of collagen providing fibrinogen is present. This response to collagen can be blocked with aspirin but not with a mixture of creatine phosphate/creatine phosphokinase. Upon a second exposure to thrombin, thrombin-pretreated platelets do not change their shape and do not undergo aggregation. Thrombin-pretreated platelets will not retract a thrombin-induced fibrin clot unless ADP, sodium arachidonate, the ionophore A23, 187 or collagen are added together with thrombin. The ability of thrombin-treated platelets to adhere to the exposed subendothelial surface of the rabbit aorta is reduced, compared with untreated control platelets. The thrombin-treated platelets shorten the bleeding time of thrombocytopenic rabbits. However, the are not as effective in shortening the bleeding time as normal control platelets. When injected into rabbits with a normal platelet count, the thrombin-treated platelets that circulate after infusion survive for the same length of time as untreated control platelets. These findings indicate that thrombin-induced platelet aggregation with extensive release of granule constituents is not irreversible and that thrombin treatment does not cause irreversible damage of all platelets that would lead to their immediate elimination from the circulation. Furthermore, these platelets can still be haemostatically effective. It is conceivable that platelets that have lost their amine storage granule contents during a release reaction in vivo, such as may occur in certain cases of intravascular coagulation and repeated episodes of thrombosis, may be found in the circulation of man.

Adenosine Diphosphate↗
PubMed1976

Effects of sodium periodate on platelet functions.

Removal of N-acetylneuraminic acid from the platelet surface causes rapid removal of platelets from the circulation but causes little change in other platelet functions. We have now investigated the effects of sodium periodate which is thought to oxidize the sialic acid of glycoproteins on cell surfaces and has been shown to affect the functions of other cells. NaIO4 (1 to 10 mm) caused aggregation of stirred suspensions of washed platelets from rabbits. Calcium was required in the suspending medium for NaIO4-induced aggregation. Aggregation was not accompanied by the release of amine storage granule contents nor by cell lysis. Aggregation induced by NaIO4 was not inhibited by creatine phosphate-creatine phosphokinase, by platelet inhibitors that raise platelet cyclic AMP levels such as prostaglandin E1 or methylxanthines, by agents that modify platelet surface--SH groups (N-ethylmaleimide, p-chloromercuribenzene sulfonate), nor by cytochalasin B and/or colchicine which interfere with platelet contractile processes. Drugs such as acetylsalicyclic acid, penicillin G, or cephalothin had no effect on NaIO4-induced aggregation. NaIO4-induced aggregation was practically independent of platelet metabolism since it was not affected by low temperatures and was only slightly inhibited by a combination of antimycin and iodoacetate. Periodate treatment enhanced CO2 production by platelets. When rabbit platelets were pretreated, without stirring, with NaIO4 (0.01 to 1 mm), they did not aggregate. They retained their disc shape and granule contents. However, this pretreatment with NaIO4 inhibited aggregation induced by ADP and inhibited both aggregation and release induced by collagen, thrombin, arachidonic acid, and the ionophore A23,187. The extent of inhibition corresponded to the concentration of NaIO4 used to pretreat the platelets. In contrast, concanavalin A-induced aggregation was unchanged by NaIO4 pretreatment. When NaIO4 oxidation was followed by sodium borohydride (NaBH4) reduction, the effects caused by NaIO4 pretreatment on ADP-induced aggregation and collagen- or thrombin-induced aggregation and release were partially reversed. Pretreatment with NaIO4 also diminished the rate of serotonin uptake and decreased the ability of platelets to adhere to collagen-coated surfaces or to the subendothelial structures of the rabbit aorta. Platelets which had been treated with NaIO4 and then reinfused into rabbits did not survive, and in this way were similar to platelets from which surface sialic acid had been removed by neuraminidase treatment. Since NaIO4 has been shown to oxidize sialic acid on red cell membranes, it seems probably that alteration of surface sialic acid resulted in recognition of the periodate-treated platelets as "foreign" by the reticuloendothelial system. When NaIO4 oxidation was followed by NaBH4 reduction, platelet survival returned toward normal values.

Adenosine Diphosphate↗