• Genomics & Informatics
• /
• v.12 no.4
• /
• pp.225-230
• /
• 2014

Platelets are derived from the fragments that are formed from the cytoplasm of bone marrow megakaryocytes-small irregularly shaped anuclear cells. Platelets respond to vascular damage, contracts blood vessels, and attaches to the damaged region, thereby stopping bleeding, together with the action of blood coagulation factors. Platelet activation is known to affect genes associated with vascular risk factors, as well as with arteriosclerosis and myocardial infarction. Here, we performed a genome-wide association study with 352,228 single-nucleotide polymorphisms typed in 8,842 subjects of the Korea Association Resource (KARE) project and replicated the results in 7,861 subjects from an independent population. We identified genetic associations between platelet count and common variants nearby chromosome 4p16.1 ($p=1.46{\times}10^{10}$, in the KIAA0232 gene), 6p21 ($p=1.36{\times}10^{-7}$, in the BAK1 gene), and 12q24.12 ($p=1.11{\times}10^{-15}$, in the SH2B3 gene). Our results illustrate the value of large-scale discovery and a focus for several novel research avenues.

• BMB Reports
• /
• v.52 no.7
• /
• pp.434-438
• /
• 2019

We have previously reported the effects of 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a synthetic phospholipid, on megakaryocytic differentiation of myeloid leukemia cells. Here, we demonstrate that (R)-TEMOSPho enhances megakaryopoiesis and plateletogenesis from primary hematopoietic stem cells (HSCs) induced by thrombopoietin (TPO). Specifically, we demonstrate at sub-saturation levels of TPO, the addition of (R)-TEMOSPho enhances differentiation and maturation of megakaryocytes (MKs) from murine HSCs derived from fetal liver. Furthermore, we show that production of platelets with (R)-TEMOSPho in combination with TPO is also more efficient than TPO alone and that platelets generated in vitro with these two agents are as functional as those from TPO alone. TPO can thus be partly replaced by or supplemented with (R)-TEMOSPho, and this in turn implies that (R)-TEMOSPho can be useful in efficient platelet production in vitro and potentially be a valuable option in designing cell-based therapy.

• Biomedical Science Letters
• /
• v.27 no.3
• /
• pp.187-194
• /
• 2021

Platelets are derived from fragments formed in the cytoplasm of bone marrow megakaryocytes. Platelet count (PLT) can be altered by factors such as platelet production, destruction, and inflammation. In a previous study, the significant single nucleotide polymorphisms (SNP) were reported by the genome-wide association study (GWAS) for PLT in Koreans. In this study, it was confirmed whether significant SNPs were replicated in the HEXA (The Health Examinees) cohort. As a result, the SNPs of the THPO (rs6141), BAK1 (rs210314, rs9296095), GGNBP1 (rs75080135), ACAD10 (rs6490294), and ABCC4 (rs4148441) were significantly correlated with PLT (P < 10^-8). At the same time, it was confirmed that the direction of influence was the same according to the genotype. In conclusion, it can be seen that common SNPs are associated with the platelet count regardless of the cohort for Koreans.

• Clinical and Experimental Pediatrics
• /
• v.65 no.4
• /
• pp.182-187
• /
• 2022

We frequently encounter newborn infants with thrombocytosis in the neonatal intensive care unit. However, neonatal thrombocytosis is not yet fully understood. Thrombocytosis is more frequently identified in newborns and young infants, notably more often in those younger than 2 years than in older children or adults. The production of megakaryocytes (megakaryopoiesis) and platelets (thrombopoiesis) is mainly regulated by thrombopoietin (TPO). Increased TPO levels during infection or inflammation can stimulate megakaryopoiesis, resulting in thrombopoiesis. TPO concentrations are higher in newborn infants than in adults. Levels increase after birth, peak on the second day after birth, and start decreasing at 1 month of age. Initial platelet counts at birth increase with gestational age. Thus, preterm infants have lower initial platelet counts at birth than late-preterm or term infants. Postnatal thrombocytosis is more frequently observed in preterm infants than in term infants. A high TPO concentration and low TPO receptor expression on platelets leading to elevated plasma-free TPO, increased sensitivity of megakaryocyte precursor cells to TPO, a decreased red blood cell count, and immaturity of platelet regulation are speculated to induce thrombocytosis in preterm infants. Thrombocytosis in newborn infants is considered a reactive process (secondary thrombocytosis) following infection, acute/chronic inflammation, or anemia. Thrombocytosis in newborn infants is benign, resolves spontaneously, and, unlike in adults, is rarely associated with hemorrhagic and thromboembolic complications.

• Journal of Chest Surgery
• /
• v.13 no.3
• /
• pp.306-311
• /
• 1980

Pure red cell aplasia is unusual cause of anemia and a selective aplastic disorder that affects the erythroid series of the bone marrow. Fifty percent of all patients with red cell aplasia will have a thymoma. Twenty-five to 30% of those who undergo thymectomy will be cured. A 57-years-old man was admitted to the medical department of Korea University hospital with complaints. Physical examination reveals a sick looking man with a pale lip, anemic conjunctiva and subicteric sclera. On auscultation, coarse breathing sound and moist rale was heard on the right lung field. Neither the liver nor spleen was palpable. A blood count showed the erythrocytes to number 2,640,000/mm3 and hemoglobin to be 7.0gm/dl. A white blood cell count was 5,000/mm3 and a platelet count was 328,000/mm3 Reticulocyte count was 0.7%. Examination of the peripheral blood smear showed the red cell, to be normocytic and normochromic. Urine sugar was three positive and GTT was positive. The anterior-posterior and lateral view of Chest X-ray was suggestive of an anterior mediastinal mass. A bone marrow biopsy reveals absence of red cell precursors and a normal myeloid series and megakaryocytes. At thoracotomy in May 1980 an encapsulated, lobulated, benign thymoma, which measured 5x7x5 cm was removed, microscopic examination showed it was of the spindle cell type. The postoperative course was uneventful, but the patient never had a return of hemoglobin to the blood. The patient was discharged on the postoperative] 3 days. At postoperative 1 month, the patient was readmitted for bone marrow study and had no return of red cells to bone marrow. At now, patient has been treated with steroid and the further follow up study will be needed.

• Korean Journal of Veterinary Research
• /
• v.41 no.3
• /
• pp.287-292
• /
• 2001

It has been known that the hemolymph node is one of the lymphoid organs found normally in ruminants and some rodents, and this organ shares morphological and functional characteristics of lymph node and spleen. To clanify the rigorous definition of morphological structures and functions of the hemolymph node in Wistar Kyoto(WKY)rats, we examined these organs of WKY rats gross anatomically and light microscopically. The hemolymph nodes were normally found in the abdominal cavity and in the neck of WKY rats. This organ was surrounded by a thin connective tissue capsule and there was a hilus. The parenchyma comprised a cortex of lymphatic nodules and diffuse lymphatic tissues, and a medulla of diffuse lymphatic tissues arranged in cords. Afferent and efferent lymph vessels were observed but there was no extensive subcapsular and medullary sinuses. These sinuses were filled with erythrocytes. The stroma of hemolymph nodes was composed of reticular cells and fibers, and many lymphocytes, granulocytes, erythrocytes, plasma cells, macrophages and megakaryocytes were supported by the reticular network. The above findings suggest that the hemolymph nodes of WKY rats may take part in blood formation, blood filtration and immune reaction.

• The Journal of Korean Medicine
• /
• v.22 no.3
• /
• pp.156-168
• /
• 2001

Objectives : To evaluate the diverse actions of stimulation on the hematopoietic system, 4 formulas (KH I, KH 2, KH 3, KH 4) were studied. Method and Result : RT-PCR was performed to measure the gene expression of hematopoietic cytokines (TPO, GM-CSF, SCF, IL-3). When bone marrow cells were treated with KH 1, 2, 3, 4, the gene expressions of TPO, SCF, IL-3, and GM-CSF were increased. Flow cytometric analysis was performed to measure the expression of CD34+ cell activity. After 72 hrs culture supplemented with KH 1, 2, 3, 4, the percent of CD34+ cell of KH 2, 3, 4 were increased. To measure the expression of colony forming units - granulocyte erythrocytes, macrophages, megakaryocytes (CFU-GEMM) and burst forming unit-erythroid (BFU-E), semisolid clonogenic assay was performed. After 14 days of culture the number of CFU-GEMM and BFU-E of KH I, 2, 3, 4 were significantly increased compared to those of EPO groups (KH 1 P<0.0l, KH 2 P<0.05, KH 3 P<0.001, KH 4 P<0.0l). To determine the intracelluar TPO expression by KH 3, KH 4 in bone marrow cells, intracelluar staining and flow cytometric analysis were performed. After 24 hrs cultures, the TPO expression of the KH 3 and KH 4 treated groups were increased over those of the controlled groups (control : 50%, KH 3 : 87%, KH 4 : 78%). Conclusion : These results suggest that KH I, KH 2, KH 3, KH 4 have hematopoietic effects through increasing the production of hematopoietic cytokines and stimulating the activity of $CD34^{+}$ cells. This study also shows that KH 3 has a more effective hematopoietic effect than KH 1, 2, 4. These results suggest that the formulas (KH I, 2, 3, 4) can be applied to the patients with inappropriate hematopoietic system, and that KH 3 can be the most effective formula among these 4 in treating bone marrow disease in clinics.

• Korean Journal of Veterinary Research
• /
• v.40 no.4
• /
• pp.671-675
• /
• 2000

It has been known that the hemolymph node is one of the lymphoid organs found normally in ruminants and some rodents, and this organ shares morphological and functional characteristics of lymph node and spleen. To clarify the rigorous definition of morphological structures and functions of the hemolymph node in Sprague-Dawley(SD) rats, we examined these organs of SD rats gross anatomically and light microscopically. The hemolymph nodes were normally found in the abdominal cavity and in the neck of SD rats. This organ was surrounded by a thin connective tissue capsule and there was a hilus. The parenchyma comprised a cortex of lymphatic nodules and diffuse lymphatic tissues, and a medulla of diffuse lymphatic tissues arranged in cords. Afferent and efferent lymph vessels were observed but there was no extensive subcapsular and medullary sinuses. These sinuses were filled with erythrocytes. The stroma of hemolymph nodes was composed of reticular cells and fibers, and many lymphocytes, granulocytes, erythrocytes, plasma cells, macrophages and megakaryocytes were supported by the reticular network. The above findings suggest that the hemolymph nodes of SD rats may take part in blood formation, blood filtration and immune reaction.

• Korean Journal of Veterinary Research
• /
• v.33 no.2
• /
• pp.327-336
• /
• 1993

Present experiments were undertaken in order to clarify the effect of splenectomy on the hematology and marrow megakaryocyte picture and to know the genesis of postsplenectomy thrombocytosis in dogs. Six mongrel dogs weighing 8.5~18㎏ were used, of which three were splenectomized and the other three were laparotomized for comparison. Erythrocyte count, total and differential leukocyte counts, thrombocyte count and packed cell volume measurement were made using the blood samples. In addition, bone marrow samples obtained from the femur at 7th and 23rd day of the operation were examined for the number per low-power field, the diameter, and the distribution frequency of the megakaryocyte. From these experiments, following results were obtained : Erythrocyte count and packed cell volume showed significant decrease beginning on the 15th day of splenectomy. Total and differential leukocyte counts showed marked increase for the first 2 days of postsplenectomy. The thrombocyte count of splenectomized dogs increased from the 2nd day of the operation, reached to the peak count on the 15th day, and returned to the preoperation count by the 28th day. The megakaryocyte count per low-power field of the biopsied preparation increased in according to the increase in thrombocyte count. The megakaryocyte diameter of splenectomized dog showed no increase on the 7th or 23rd day of the operation. However, the distribution frequency of the larger megakaryocyte was higher in the splenectomized dogs than in the laparotomized dogs. The total plasma protein concentration showed no significant change after splenectomy or laparotomy. From these results, it may be concluded that the postsplenectomy thrombocytosis results from the increased megakaryocytopoesis or the activated thrombocytopoesis of the marrow megakaryocytes.

• Molecules and Cells
• /
• v.22 no.1
• /
• pp.70-77
• /
• 2006

Platelets are anucleate cytoplasmic fragments derived from bone marrow megakaryocytes, and endothelial cells constitute the barrier between bloodstream and adjacent tissues. Although platelets are thought to regulate the biological functions of endothelial cells, the molecular mechanisms involved are poorly understood. With human umbilical vein endothelial cells and freshly isolated platelets, we established an in vitro model of platelet-induced endothelial cell proliferation. Platelets stimulated endothelial cell proliferation in a dose-dependent manner and transwell experiments with semi-permeable membranes suggested that direct cell-to-cell contacts were required. We developed mAbs against platelets and selected a mAb that blocks their proliferative effect. We purified the antigen by immunoprecipitation and identified it by Q-TOF MS analysis as the tetraspanin CD9. Since both platelets and endothelial cells expressed CD9 strongly on their surfaces we carried out a pre-treatment experiment that showed that CD9 molecules on the endothelial cells participate in the mitogenic effect of the platelets. The inhibitory effect of our mAb was comparable to that of a well-known functional anti-CD9 mAb. These results suggest that the tetraspanin CD9 plays an important role in endothelial regeneration.