Peripheral Red Blood Cell Counts Research Articles

Microarray analysis of PBMC after Plasmodium falciparum infection: Molecular insights into disease pathogenesis.

To find out host gene expression profiles after malarial infection. Further time-course microarray analysis of peripheral blood mononuclear cells focusing on malaria pathogenesis was performed. Up-regulation of coagulation-related genes, heat shock proteins, glycolytic enzymes, glucose transporters, and vacuolar H(+)-ATPases was found in acute febrile malaria. In early malaria, prior to detectable parasitemia, CD36 and ICAM1 were up-regulated. During acute malaria, there is correlation between IL-1β and heat shock proteins. CD163, a hemoglobin scavenger receptor, was up-regulated in acute malaria to potentially facilitate free hemoglobin up-take by leukocytes. In acute malaria, high MafB gene expression was negatively correlated with hemoglobin and platelet counts. Consistent with hemoglobin down-regulation, peripheral red blood cell counts tended to increase during acute malaria. Up-regulations of red blood cell and leukocyte binding mediators like CD36, ICAM1, thrombospondin, and thrombomodulin may contribute to the pathogenesis of cerebral malaria. Similarly, up-regulation of correlated glycolytic enzymes, glucose transporter and H(+)-ATPases may contribute to the hypoglycemia and metabolic acidosis frequently observed in serious malaria patients. Overall gender effects on gene expression profiles between male and female were not apparent, except for some hemoglobins were significantly down-regulated in male versus female, which suggesting males are prone to malaria-related anemia. Leukocyte gene expression profiles can explain the pathogenesis of malarial complication such as fever, metabolic acidosis, hypoglycemia, anemia, and coagulopathy.

Study of pathophysiology of pulmonary circulation in polycythemia using scintigraphy

In order to evaluate the pathophysiology of pulmonary circulation in polycythemia, Tl-201 myocardial scintigraphy and perfusion lung scintigraphy with 99m-Tc MAA were performed in 19 cases with polycythemia including polycythemia rubra vera and in 11 cases with secondary polycythemia due to pulmonary diseases. Tl-201 lung uptake, right ventricular visualization and pulmonary perfusion impairment were studied. In the 19 cases, Tl-201 lung uptake was observed in all cases and 54.5% of them showed moderate lung uptake. The grade of right ventricular visualization was moderate in one case and slight in 16 cases; right ventricular hypertrophy was shown in 89.5% of all cases by Tl-201 scintigraphy, only one of which showed right ventricular hypertrophy on electrocardiography. Abnormalities of lung perfusion consisted of scattered small areas of hypoperfusion in 36.8%, peripheral hypoperfusion in 78.9% and uneven distribution of pulmonary perfusion in 94.7%. The degree of hypoperfusion was slightly related to decrease in FEV1.0%, V25 and PaO2 and increase in circulating blood volume and peripheral red blood cell counts. Abnormalities of pulmonary function consisted of increased RV/TLC in 50.0%, increased CV/VC in 35.7% and decreased V25 in 36.8%. Arterial blood gases showed hypoxemia in 57.1%, the degree of which was slightly related to increase in RV/TLC and CV/VC and decrease in V25. Cases of secondary polycythemia due to pulmonary diseases showed more marked right ventricular visualization, pulmonary perfusion impairment and abnormalities of various kinds of pulmonary function than polycythemia rubra vera cases.(ABSTRACT TRUNCATED AT 250 WORDS)

A mild transient decrease of peripheral red blood cell counts induced by a suprapharmacological dose of pegylated human megakaryocyte growth and development factor in rats.

Previous studies have shown that pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) at suprapharmacological dose induces a mild transient decrease of red blood cell counts according to thrombopoiesis in normal mice. To unravel the mechanism underlying this mild transient decrease of red blood cells, we have studied the effect of PEG-rHuMGDF on the circulating plasma and blood volume, and the serum biochemical parameters of anaemia and splenectomy. Also, we have performed histological studies of the bone marrow and the spleen of PEG-rHuMGDF-treated rats. PEG-rHuMGDF (300 microg kg(-1)]) or vehicle was subcutaneously administered to rats once a day for up to five days. From day 6 after the start of PEG-rHuMGDF administration, the platelet counts and plateletcrit levels were significantly increased, reaching peak values on day 10, and recovering to normal by day 20. The red blood cell counts and the haematocrit levels were significantly decreased on day 6 to 13. The decreases in red blood cell levels and haematocrit produced by PEG-rHuMGDF treatment were mild and had recovered by day 15. The plasma and blood volumes were significantly increased on day 10 in PEG-rHuMGDF-treated rats. No alteration of the serum biochemical parameters for anaemia, iron or total bilirubin, were observed on day 10. The histological examination on day 10 revealed a marked increase in megakaryocytes and a slight decrease in erythropoiesis in the bone marrow of rats that received PEG-rHuMGDF (300 microg kg(-1)). There was also a slight increase in splenic megakaryocytes and erythropoiesis. The decrease of red blood cells by PEG-rHuMGDF was not affected by splenectomy. These results suggest that the mild transient decrease of red blood cells induced by PEG-rHuMGDF treatment for up to five days is based mainly on the increases in the plasma and blood volume. These events are secondary changes due to the regulation of the excess production of megakaryocytes in the marrow and the peripheral platelets.

The Influence of Androgen Deprivation Therapy on Metabolism in Patients with Prostate Cancer

The effects of androgen deprivation therapy (ADT) include not only suppression of tumor growth, but also adverse effects on various bodily functions. The aim of this study was to determine the metabolic effects of ADT in patients with nonmetastatic prostate cancer. Forty-nine men with prostate cancer were treated with ADT before beginning radical therapy for 6 months. Body weight, peripheral red blood cell counts, hemoglobin, hematocrit, fasting blood sugar, serum total cholesterol, blood urea nitrogen, uric acid, compensated calcium, inorganic phosphorus, bone-specific alkaline phosphatase, urinary deoxypyridinoline, and radial bone density determined using dual energy x-ray absorptiometry were examined before and 6 months after ADT treatment. Body weight (P = 0.037) and the levels of fasting blood sugar (P = 0.014), serum total cholesterol (P = 0.017), blood urea nitrogen (P = 0.030), compensated calcium (P < 0.001), inorganic phosphorus (P < 0.001), bone-specific alkaline phosphatase (P < 0.001), and compensated urinary deoxypyridinoline (P < 0.001) increased significantly. Peripheral red blood cell counts (P < 0.001), hemoglobin level (P < 0.001), hematocrit (P < 0.001), uric acid (P < 0.001), and radial bone density (P = 0.023) decreased significantly. These effects of ADT on various bodily functions warrant systematic study in clinical trials. We should be aware of the far-reaching consequences of ADT and incorporate strategies for preventing and managing adverse effects into routine practice.

Increased apoptosis in acquired sideroblastic anaemia

Idiopathic acquired sideroblastic anaemias (IASAs) form a subgroup of the myelodysplastic syndromes and are characterized by mitochondrial iron accumulation, bone marrow erythroid hyperplasia and decreased peripheral red blood cell counts. Increased intramedullary apoptosis of erythroid precursors is presumed to constitute the pathophysiological mechanism explaining this ineffective erythropoiesis, but if and how mitochondrial dysfunction is implicated in this process is currently unknown. We therefore studied bone marrow precursor cells obtained from nine patients with IASA for (i) caspase 3 activity, (ii) numbers of Annexin V- and 7-amino-actinomycin-positive cells, (iii) numbers of cells with diminished mitochondrial membrane potential, Delta Psi(m), and (iv) numbers of cells producing reactive oxygen species (ROS), and we compared the results with those of five normal bone marrow samples. Compared with controls, we found increased caspase 3 activity in all IASA samples, which correlated with increased numbers of Annexin-V-positive cells (r = 0.7). Analysis of different subpopulations showed increased apoptosis in erythroid populations compared with myeloid and/or lymphoid populations in five out of nine cases, and increased apoptosis in the last two populations in four out of nine cases. As evidence of mitochondrial dysfunction, Delta Psi(m) was found to be diminished in the erythroid subpopulations of all cases of IASA (66.6 +/- 17% vs. 34.6 +/- 12% in normals). Delta Psi(m) decrease was correlated to Annexin V positivity (r = 0.7). Astonishingly, no difference was found between IASA and normal bone marrows with regard to the number of ROS-producing cells. In fact, both groups exhibited a similar low proportion of ROS production (10.3 +/- 7% in normals vs. 6.8 +/- 5% in IASA). Taken together, our results show that mitochondria are clearly implicated in the apoptotic process in IASA patients. Whether this is a result of an intramitochondrial defect (e.g. Fe accumulation, secondary to mitochondrial or nuclear DNA mutations) or is secondary to an extracellular stimulus [e.g. tumour necrosis factor (TNF), Fas ligand (FasL)] remains to be determined.

The Presence of Novel Amino Acids in the Cytoplasmic Domain of Stem Cell Factor Results in Hematopoietic Defects inSteel17H Mice

Stem cell factor (SCF) is expressed as an integral membrane growth factor that may be differentially processed to produce predominantly soluble (S) (SCF248) or membrane-associated (MA) (SCF220) protein. A critical role for membrane presentation of SCF in the hematopoietic microenvironment (HM) has been suggested from the phenotype of the Steel-dickie(Sld) mice, which lack MA SCF, and by studies performed in our laboratory (and by others) using long-term bone marrow cultures and transgenic mice expressing different SCF isoforms.Steel17H (Sl17H) is an SCF mutant that demonstrates melanocyte defects and sterility in males but not in females. The Sl17H allele contains a intronic mutation resulting in the substitution of 36 amino acids (aa’s) in the SCF cytoplasmic domain with 28 novel aa’s. This mutation, which affects virtually the entire cytoplasmic domain of SCF, could be expected to alter membrane SCF presentation. To investigate this possibility, we examined the biochemical and biologic properties of the Sl17H-encoded protein and its impact in vivo and in vitro on hematopoiesis and on c-Kit signaling. We demonstrate that compound heterozygous Sl/Sl17H mice manifest multiple hematopoietic abnormalities in vivo, including red blood cell deficiency, bone marrow hypoplasia, and defective thymopoiesis. In vitro, both S and MA Sl17H isoforms of SCF exhibit reduced cell surface expression on stromal cells and diminished biological activity in comparison to wild-type (wt) SCF isoforms. These alterations in presentation and biological activity are associated with a significant reduction in the proliferation of an SCF-responsive erythroid progenitor cell line and in the activation of phosphatidylinositol 3-Kinase/Akt and mitogen-activated protein-Kinase signaling pathways. In vivo, transgene expression of the membrane-restricted (MR) (SCFX9/D3) SCF in Sl/Sl17H mutants results in a significant improvement in peripheral red blood cell counts in comparison toSl/Sl17H mice.

The Presence of Novel Amino Acids in the Cytoplasmic Domain of Stem Cell Factor Results in Hematopoietic Defects inSteel17H Mice

AbstractStem cell factor (SCF) is expressed as an integral membrane growth factor that may be differentially processed to produce predominantly soluble (S) (SCF248) or membrane-associated (MA) (SCF220) protein. A critical role for membrane presentation of SCF in the hematopoietic microenvironment (HM) has been suggested from the phenotype of the Steel-dickie(Sld) mice, which lack MA SCF, and by studies performed in our laboratory (and by others) using long-term bone marrow cultures and transgenic mice expressing different SCF isoforms.Steel17H (Sl17H) is an SCF mutant that demonstrates melanocyte defects and sterility in males but not in females. The Sl17H allele contains a intronic mutation resulting in the substitution of 36 amino acids (aa's) in the SCF cytoplasmic domain with 28 novel aa's. This mutation, which affects virtually the entire cytoplasmic domain of SCF, could be expected to alter membrane SCF presentation. To investigate this possibility, we examined the biochemical and biologic properties of the Sl17H-encoded protein and its impact in vivo and in vitro on hematopoiesis and on c-Kit signaling. We demonstrate that compound heterozygous Sl/Sl17H mice manifest multiple hematopoietic abnormalities in vivo, including red blood cell deficiency, bone marrow hypoplasia, and defective thymopoiesis. In vitro, both S and MA Sl17H isoforms of SCF exhibit reduced cell surface expression on stromal cells and diminished biological activity in comparison to wild-type (wt) SCF isoforms. These alterations in presentation and biological activity are associated with a significant reduction in the proliferation of an SCF-responsive erythroid progenitor cell line and in the activation of phosphatidylinositol 3-Kinase/Akt and mitogen-activated protein-Kinase signaling pathways. In vivo, transgene expression of the membrane-restricted (MR) (SCFX9/D3) SCF in Sl/Sl17H mutants results in a significant improvement in peripheral red blood cell counts in comparison toSl/Sl17H mice.

The effect of vitamin D 3 and 1,25-dihydroxyvitamin D 3 on the toxic symptoms of cadmium exposed rats

The effects of vitamin D 3 and 1, 25-dihydroxyvitamin D 3 on the toxic symptoms of cadmium exposed young rats fed a modified AIN diet were studied for 14 weeks. All rats exposed to 20 ppm and 40 ppm of cadmium ions (Cd 2+) in the drinking water displayed smaller weight gains than the control group. Both vitamin D 3 and 1, 25 dihydroxyvitamin D 3 increased the weight gain in weeks 7–14 over their respective Cd 2+ controls. Relative weights of liver and spleen per 100 gm body weight showed no apparent response to Cd 2+ but significant increases in the weights of both kidney and testis were observed. Both vitamin D 3 and 1, 25 dihydroxyvitamin D 3 showed a protective effect on the kidney and vitamin D 3 on the testis. Relative femur wet weights were higher in the Cd 2+-exposed smaller rats when compared to the controls. Analysis of the femurs revealed an increase in water and a decrease in mineral content with Cd 2+ exposure, although no difference in organic matter was observed. These findings were considered to be symptomatic of osteoporosis. Neither vitamin D 3 nor 1, 25 dihydroxylvitamin D 3 consistently altered the weights or composition of the femurs at the concentrations we tested. Peripheral blood studies revealed that Cd 2+ increased the mononuclear cell: segmented cell ratio by inhibiting myelopoiesis. Although no changes in hematocrit or peripheral red blood cell counts were noted, rats exposed to 40 ppm Cd 2+ for 14 weeks showed evidence of erythrocyte hypochromia with intracellular non-heme iron inclusions.

Immunological and neurobiochemical alterations induced by repeated oral exposure of phenol in mice

Phenol, a major metabolite of benzene, is a potentially immunotoxic and neurotoxic substance of environmental significance. Male CD-1 mice were continuously exposed to 0, 4.7, 19.5, and 95.2 mg phenol/l in drinking water for 4 weeks. Various immune functions were evaluated and levels of selected neurotransmitters and metabolites measured in discrete brain regions. The doses of phenol did not produce any overt clinical signs of toxicity; peripheral red blood cell counts and hematocrits decreased. A dose of 95.2 mg/l suppressed the stimulation of cultured splenic lymphocytes by lipopolysaccharide, pokeweed mitogen, and phytohemagglutinin and the response in mixed lymphocyte cultures. The two high doses suppressed antibody production response to the T cell-dependent antigen (sheep erythrocytes), as determined by plaque-forming cells, and serum antibody levels. Mice treated with phenol had lower levels of neurotransmitters in several brain regions. In the hypothalamus, a major norepinephrine-containing compartment, the concentrations of norepinephrine significantly decreased by 29 and 40% in groups dosed with 19.5 and 95.2 mg/l, while dopamine concentrations decreased in the corpus striatum by 21, 26, and 35% at 4.7, 19.5 and 95.2 mg/l, respectively. Phenol also decreased 5-hydroxytryptamine in the hypothalamus, medulla oblongata, midbrain and corpus striatum. Levels of monoamine metabolites decreased in the hypothalamus (5-hydroxyindoleacetic acid), midbrain (vanillylmandelic acid), corpus striatum (vanillylmandelic acid and dihydroxyphenylacetic acid), cortex (vanillylmandelic acid), and cerebellum (dihydroxyphenylacetic acid).

Erythrocyte life span in small animals; comparison of two methods employing radioiron.

Erythrocyte life span in small animals; comparison of two methods employing radioiron.