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D M Klachko

Publications and source records attributed to D M Klachko.

7 recordsLinked to original sources

Hypersensitivity of diabetic human platelets to platelet activating factor.

Platelet activating factor (PAF) stimulated aggregation and [32P]-phosphatidic acid (PA) production was compared in normal and diabetic human subjects in platelet rich plasma. The concentration of PAF for half maximal (50%) aggregation of normal and diabetic platelets was 50 nM and 8 nM, respectively. PAF stimulated [32P]-PA production (a metabolite of phospholipase C pathway) was also greater in the platelets from diabetic subjects. This [32P]-PA production was inhibited by the PAF receptor antagonists SRI-63441 and SRI-63675. When the levels of glycosylated hemoglobin (HbA1c) were compared with the PAF stimulated [32P]-PA production a significant relationship was observed. These studies have demonstrated for the first time that diabetic human platelets show hypersensitivity to PAF in both aggregation and [32P]-PA production compared to normal subjects. This may be a result of some modification in phospholipid turnover mechanism and is receptor mediated. Further, the relationship of the degree of aggregation and [32P]-PA production to the level of HbA1c suggest that the insulin deficiency may contribute to these effects.

Blood Platelets

Effect of a microcomputer-based registry on adult immunizations.

A survey of patients attending the Cosmopolitan International Diabetes Center showed that one third of those born prior to 1935 did not know their immunization status, and only 56% of this group remembered ever receiving tetanus vaccine. In contrast, of those born after 1935, 98% gave a history of being vaccinated for tetanus, either as a child (76%) or as an adult (22%). Eight of the 35 patients who could not remember or denied receiving pneumococcal vaccine had in fact received it. Most patients could remember whether and when they had received influenza vaccine. A microcomputer-based registry was used to generate summaries of clinical information at each patient visit. These summaries included prevention-related items. There was a three- to five-fold increase in immunization rates when the dates of the most recent vaccinations were prominently displayed on the summary at the time of each visit.

Adult

Response to platelet-activating factor in human platelets stored and aged in plasma. Decrease in aggregation, phosphoinositide turnover, and receptor affinity.

Human platelet concentrates were stored in polyolefin bags at 22 to 24 degrees C on a horizontal shaker for up to 8 days. At different intervals, aliquots of platelet-rich plasma (PRP) were removed aseptically and five variables, i.e., platelet counts, morphology, platelet-activating factor (PAF)-stimulated aggregation, phosphoinositide turnover, and [3H]PAF binding to platelet receptors, were studied. The number of platelets did not change during the 8 days of storage. Scanning electron microscopy of the platelets revealed a gradual morphologic change from biconcave flat discs to irregular, crenated forms. The PAF-induced aggregation of platelets declined with time of storage. A decrease to 50 percent of the Day 1 aggregatory response to PAF was evident on Day 2, and there was a further decline to about 20 percent by Day 6. Similarly, PAF receptor-coupled phosphoinositide turnover, as monitored by 32P incorporation into individual phosphoinositides, decreased dramatically with storage. After 2 to 3 days of storage, the phosphoinositide turnover was reduced to 50 percent of the original response, and it continued to decline to about 25 percent of original response by Day 5 or 6. The binding of [3H]PAF to washed human platelets indicated subtle changes between Days 2 and 4, which became more noticeable by Day 6. These results have raised the possibility of changes in the number of the receptors and/or their affinity for the ligand during storage. We conclude that although the number of platelets was maintained during storage for 8 days, a general deterioration of their responses to PAF occurred at the levels of cell surface receptor, transmembrane signaling (phosphoinositide turnover), and response (aggregation).

Binding, Competitive