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J W Akkerman

Publications and source records attributed to J W Akkerman.

At least 127 records · Page 7Linked to original sources
PubMed1977

A new variant of glucosephosphate isomerase deficiency: GPI-Kortrijk.

A new case of glucosephosphate isomerase deficiency in a Belgian family is described. The activity of the enzyme was decreased to about 25-30% of the normal value. Characterization of the defect enzyme showed a decreased thermostability. Heating of the enzyme at 45 degrees C showed a loss of activity of 50% after 90 min. The pH-optimum and the KM-value for fructose 6-phosphate were normal. The electrophoretic pattern showed a faster migration. The variant described here differs from all known variants. Therefore we propose to give to this new variant the name GPI-Kortrijk.

Anemia, Hemolytic, Congenital Nonspherocytic↗
PubMed1977

A patient with purine nucleoside phosphorylase deficiency: enzymological and metabolic aspects.

1. Enzymological and metabolic data in a patient with nucleoside phosphorylase (NP) deficiency are described. 2. Incubation of intact NP-deficient red cells with [14C]adenosine showed a rapid uptake and conversion to inosine. Almost no radioactivity was incorporated in the adenosine nucleotides and no hypoxanthine labeling could be detected. 3. Incubation with [14C]inosine resulted in a rapid conversion to IMP in the normal intact red cells but in an accumulation of inosine in the medium with the erythrocytes of the patient, proving again that a NP deficiency is present. 4. The high PRPP level found may result from impaired consumption due to lack of substrates for the salvage enzyme HGPRT. 5. Incubation with [14C]hypoxanthine and [14C]adenine showed that normal HGPRT and APRT activities were present in the NP-deficient red cells. 6. In serum and urine of the patient the levels of inosine and guanosine were considerably increased, while the serum and urinary levels of uric acid were very low. In the two deceased sisters NP deficiency was also strongly suggested by analyses of the serum purines, of stored deep frozen samples.

Adenine↗
PubMed1977

The Hermansky-Pudlak syndrome. Evidence for a lowered 5-hydroxytryptamine content in platelets of heterozygotes.

A Dutch kindred with the Hermansky-Pudlak syndrome (HPS) is described. We show for the first time evidence of a lowered platelet 5-hydroxytryptamine content in obligate heterozygotes. Platelet ATP and ADP levels and ATP/ADP ratio were normal in these patients. Platelet aggregation with ADP, collagen and adrenaline was within the normal range. In contrast to the homozygous HPS patients the heterozygotes are normally pigmented and none has diaphanous irides, nystagmus or a bleeding tendency. All homozygous HPS patients have the typical triad of oculocutaneous albinism, pigmented macrophages in the bone marrow and a bleeding disorder, based on a platelet dysfunction. The platelets showed the typical characteristics of a storage pool deficiency. Their platelet factor 3 availability was decreased and the aggregation patterns showed an absent second wave with ADP, adrenaline and absent collagen aggregation. Platelet ADP levels were strongly decreased in all homozygous HPS patients, whereas ATP was lowered only in 3 out of 6 HPS patients. The 5-hydroxytryptamine content of their platelets was very low (15-20% of normal).

Adenosine Diphosphate↗
PubMed1976

Preparation of concentrated platelet suspensions by dehydration against polyethyleneglycol 20,000.

Gel filtered platelet suspensions were concentrated by repeated dehydration against polyethyleneglycol 20,000 followed by dialysis against slightly hypotonic buffer. This method increased the platelet concentration 2-3 times with a recovery of 80-100%. The final cell suspension closely resembled the original platelet rich plasma as tested by a number of platelet tests.

Adenosine Diphosphate↗
PubMed1975

Human platelet 6-phosphofructokinase. Relation between inhibition by Mg-ATP2-and cooperativity towards fructose 6-phosphate and investigations on the formation of a ternary complex.

Human platelet 6-phosphofructokinase (EC 2.7.1.11) shows cooperativity towards Fru-6-P and is allosterically inhibited by high Mg-ATP2- concentrations. No relation could be demonstrated between the cooperativity towards Fru-6-P and the inhibition by Mg-ATP2-. Increasing the concentrations of Mg-ATP2- only raised the apparent Km values for Fru-6-P, but did not change the Hill constants. A possible formation of a Mg-ATP2--enzyme-Fru-6-P complex during catalysis was investigated. Our calculations suggest that such a ternary complex is indeed formed during the reaction.

Adenosine Triphosphate↗
PubMed1974

Influence of Mg2.

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Adenosine Triphosphate↗
PubMedDate not supplied

Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia.

The interaction of blood platelets with collagen is generally considered to be of primary importance in the arrest of bleeding and to have a role in the pathogenesis of thrombosis and atherosclerosis. Following damage to the vascular endothelium, circulating platelets come into contact with exposed collagen fibrils in the subendothelium and spread along it; this is followed by the secretion of several biologically active substances and by aggregation of platelets. The glycoproteins of the platelet plasma membrane have an important role in the mechanisms underlying these processes. So far, two specific defects of platelet function in patients with a bleeding disorder are known to be associated with a glycoprotein defect and the study of these patients has contributed significantly to present concepts of platelet function. The glycoprotein (GP) IIB-III complex, absent or deleted in the aggregation-defective Glanzmann's thrombasthenia, has been identified as the platelet fibrinogen receptor. GPIb, which is absent in the adhesion-defective Bernard-Soulier syndrome, has been identified as the von Willebrand factor receptor on platelets. We now report a defect of the platelet plasma membrane glycoprotein composition in a patient whose platelets are totally unresponsive to collagen.

Arachidonic Acid↗
PubMedDate not supplied

Activation of sodium-proton exchange is a prerequisite for Ca2+ mobilization in human platelets.

Stimulated platelets take up sodium ions and release hydrogen ions due to activation of Na+/H+ exchange resulting in cytoplasmic alkalinization. Suppression of Na+/H+ exchange either by removal of extracellular Na+ or by application of amiloride inhibits shape change, secretion of granule contents and aggregation. The data we present here indicate that inhibition of this transport by ethylisopropyl-amiloride or by lowering extracellular sodium reduces or even completely suppresses the rise in cytoplasmic free Ca2+ concentration that is essential for platelet aggregation in response to thrombin. We also demonstrate that cytoplasmic alkalinization produced by exposure to the ionophore monensin sensitizes the human platelet response to stimulation by thrombin resulting in enhanced Ca2+ mobilization and aggregability. We conclude that an increase in intracellular pH evoked by activation of Na+/H+ counter transport is an important signal in stimulus-response coupling and forms an essential step in the cascade of events required to increase cytoplasmic free Ca2+ in platelets.

Amiloride↗
PubMedDate not supplied

Acquired secretion defect in platelets after cryopreservation in dimethyl sulfoxide.

Despite the use of preservatives, platelets are severely damaged during cryopreservation and, following freezing, function poorly in a number of in vitro tests. We report here that cryopreserved platelets show diminished aggregation in response to collagen. This may be a consequence of a secretion defect as evidenced by a 20 to 30 percent loss of dense- and alpha-granule content (p less than 0.05) and an impaired secretion mechanism. Analysis of adenine nucleotides confirmed the defect in dense granule adenosine triphosphate (ATP) and adenosine diphosphate (ADP) content (storage pool), but in addition revealed a 50 percent fall in cytosolic ATP (metabolic pool). In contrast, the adenylate energy charge, (ATP + 1/2 ADP)/(ATP + ADP + adenosine monophosphate), was normal. We concluded that platelet cryopreservation leads to a secretion defect, probably as a result of activation during freezing and thawing procedures.

Adenosine Diphosphate↗
PubMedDate not supplied

Differences in the susceptibility of platelets to freezing damage in relation to size.

Previous studies have shown that cryopreservation of normal platelets induces a reduction in the contents of secretion granules, the generation of thromboxane B2, and aggregability. The present study investigates whether these changes in the total population occur to the same extent in four size-dependent subpopulations with mean platelet volumes of 4.2, 5.7, 8.0, and 11.1 microns 3, obtained by counterflow centrifugation. Cryopreservation reduced the contents of the alpha granule markers and the generation of thromboxane B2 in the platelets from the four fractions to the same extent as in the platelets from the total suspension. Maximal aggregation of the platelets in response to collagen was measured by optical aggregation. The average decrease in light transmission after freezing was 47 +/- 3 percent (SEM) for the platelets in the total population, 40 +/- 3 percent for the largest platelets, and 65 +/- 5 percent for the smallest platelets, which indicates that aggregability was better preserved in the larger platelets than in the smaller cells. It is possible that, in the smallest platelets, a decrease in thromboxane generation of approximately 70 percent becomes rate-limiting for aggregation. Further improvements in the clinical use of freeze-preserved platelets may be sought in the preparation of concentrates with relatively high counts of large platelets.

Blood Platelets↗