Relationship between erythropoietin and erythroid colony-stimulating activity in mouse plasma.
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Animals↗
Biomedical subjects
Y Enoki
Publications and source records attributed to Y Enoki.
Inverse relationship between erythroid colony-stimulating and inhibiting activities in plasma from non-uremic anemic patients.
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Anemia↗
Relationships between %Hb F or %G gamma and the haplotypes in the beta-globin gene cluster in the normal adult Japanese and Korean populations.
Haplotypes or subhaplotypes in the beta-globin gene cluster were examined in 31 normal Japanese and 21 Korean families. Major haplotypes were VII, V, and I, which shared a common subhaplotype [+----], and occurred in 70% of the Japanese and 68% of the Koreans. Three haploypes which shared a common subhaplotype [-+-++], bearing the XmnI site 5' to the G gamma-globin gene, occurred in 13% of the Japanese and 7.3% of the Koreans. One subhaplotype [-++-+], which is closely linked to the A gamma T-globin gene, had an incidence of 6.6% in the Japanese and 20% in the Koreans. Rare subhaplotypes [---++], and [- +] which has been observed mainly in Melanesians and Polynesians, and a very rare subhaplotype [-----] were observed. The present study suggests that high or low G gamma-globin chain production is closely related to subhaplotypes [-+-++] and [+----], respectively, among the normal adult population.
Adult↗
The XmnI site 5' to the G gamma-globin gene polymorphism and its relationship to %Hb F and %G gamma in normal Japanese and Korean adults.
The ratio of fetal hemoglobin to total hemoglobin (%Hb F), the ratio of G gamma to total gamma globin (%G gamma), and the polymorphism of the XmnI site at -158 base pairs from the cap site of the G gamma-globin gene were examined in normal unrelated Japanese (n = 113) and Korean (n = 44) adults. The frequency of the presence of the XmnI site was 0.15 in the Japanese and 0.16 in the Korean population. There were statistically significant differences in the %G gamma values of the Japanese between those +/+ and those +/- or -/- at the XmnI site (p less than 0.01). The Korean %G gamma values showed a statistically significant difference (p less than 0.01) between those +/- and those -/-. The presence of the XmnI site was significantly associated with the elevation of G gamma-globin chain synthesis, but this relationship was not necessarily absolute. The absence of the XmnI site in an adult with a gamma-globin gene triplication (G gamma AG gamma A gamma/G gamma A gamma) more or less reduced the level of G gamma-globin chain synthesis, but the presence of the XmnI site in an adult with a gamma-globin gene deletion (GA gamma/G gamma A gamma) had no effects on the proportion of the two gamma-globin chains.
Adult↗
Neutralization and immunoaffinity chromatography of erythroid colony-stimulating activity in mouse plasma by an anti-erythropoietin monoclonal antibody.
A relationship between erythropoietin (EPO) and erythroid colony-stimulating activity (ECSA) in mouse plasma was examined in fetal mouse liver cell (FMLC) cultures using a monoclonal antibody (MoAb) R2 raised against recombinant human EPO. Most of the ECSA in plasma from normal, anemic, and hypoxic mice was neutralized by MoAb. This neutralization could be reversed by addition of excess of anemic plasma or by preincubation of MoAb with goat anti-mouse IgG antibody. Most of the plasma ECSA was bound to an immunoadsorbent column containing the immobilized MoAb, and the retained ECSA was completely neutralized by MoAb. The plasma ECSA and standard EPO showed parallel dose-response curves and additive effect on CFU-E stimulation. Based on these findings, we conclude that mouse plasma ECSA detected by CFU-E assay using FMLCs is mainly due to EPO.
Anemia↗
[Case study of interleukin-1 beta, tumor necrosis factor alpha and interleukin-6 production peripheral blood monocytes in patients with diabetes mellitus complicated by pulmonary tuberculosis].
Patients with diabetes mellitus (DM) show an increased susceptibility to bacterial infections due to the presence of neutrophil dysfunction. Susceptibility to tuberculosis has also been reported in such patients, however, the reason remains unclear. This study measured the production of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) by the peripheral monocytes of patients diagnosed with pulmonary tuberculosis accompanied by DM (TB+DM) and patients without DM complications (TB) using age-matched, healthy control subjects for comparison. Also examined was the relationship between cytokine production and DM control. The results were as follows: (1) The production of IL-1 beta, TNF alpha and IL-6 in TB patients was significantly higher than that observed in the healthy control subjects. (2) The production of IL-1 beta, TNF alpha and IL-6 in TB+DM patients was significantly lower than that observed in the TB patients. (3) The production of IL-1 beta and TNF alpha in TB+DM patients with poor control was significantly lower than that observed in the patients with good control. (4) The TNF alpha production had a significant inverse correlation to HbA1c in the TB+DM patients. This study demonstrated that the production of cytokines is impaired in TB+DM patients and suggests a close correlation between tuberculosis immunity and DM.
Adult↗
Developmental changes in plasma erythroid colony-stimulating activity in mice: cyclic erythropoiesis associated with rapid growth.
To establish a role of erythropoietin (Epo) in regulation of fetal and neonatal erythropoiesis, plasma erythroid colony-stimulating activity (ECSA) in developing mice was measured by an erythroid colony-forming assay using fetal mouse liver cells. The ECSA in fetal and neonatal plasmas showed dose-response curves parallel to standard Epo curve and additive effects with standard Epo on the colony formation. Most of the plasma ECSA was neutralized by an anti-Epo monoclonal antibody. These results suggest that the plasma ECSA detected by the present bioassay is predominantly due to Epo. On day 12-14 of gestation, the plasma ECSA levels were at the highest values; thereafter the levels oscillated up to the age of 4 weeks. The packed cell volume (PCV) also oscillated, but with the reverse phase. Oscillation in PCV was associated with the growth. There was an inverse relationship between plasma ECSA and PCV levels throughout the prenatal and early postnatal periods. The results indicate that erythropoiesis in fetal and neonatal mice is regulated mainly on the basis of PCV-ECSA feedback control mechanism.
Animals↗
Postnatal transition of gamma-globin gene expression in normal Japanese population.
Temporal course of postnatal changes in the gamma isoform composition of human fetal haemoglobin (HbF) was studied in 259 cord, 272 infantile and 216 adult Japanese blood samples. Reversed phase high-performance liquid chromatography was used for determination of the three isoforms of the gamma chain (A gamma T, A gamma I and G gamma), and the adult samples, usually with less than 1% of Hb F, were enriched for Hb F by an alkali denaturation-salting out procedure. The results show that the G gamma gene expression, kept at a higher and strictly-controlled level in the neonatal period, undergoes a gradual change during 1 year, beginning 3-4 months after birth, to the adult stage which is characterized by a generally lower and loosely-controlled expression of the gene. Further change seems to occur after 1 year, settling to the final adult level. The A gamma T gene frequency is estimated as 0.139 in the present Japanese adult population, and is essentially identical to the value for the newborns in the same population (0.141).
Adult↗
Oxygen consumption in resting dog gracilis muscle perfused at varying oxygen delivery.
The different response of O2 uptake (VO2) of resting skeletal muscle to the changes in blood flow has been thought to reflect a species difference. To scrutinize this notion, we investigated the relation between O2 delivery (arterial O2 content multiplied by blood flow) and VO2 in isolated dog gracilis muscle perfused solely with normal hematocrit (Ht) blood (n = 9), or alternately with normal and low Ht blood (n = 6), or alternately with normal and high Ht blood (n = 3) at varying perfusion rates. Eleven out of the 18 preparations showed an autoregulation of blood flow, and the others did not. But, in all preparations, the VO2 was delivery-independent above a critical O2 delivery (0.45 ml/(min.100 g muscle)) and showed the constant VO2 of 0.30 ml/(min.100 g), while below the critical level it turned out to be delivery-dependent. The maximal extraction ratio was 0.67. The same relationship was found with the low and high Ht perfusion. The pattern observed in dog gracilis muscle was essentially the same as that in rat gracilis muscle (KOLAR and JANSKY, 1984).
Animals↗
[Interaction between interleukin-1 and tumor necrosis factor productions by peripheral blood monocytes and nutritional disturbance in active pulmonary tuberculosis].
Malnutrition is frequently observed in patients with pulmonary tuberculosis. We have already reported the nutritional disturbance in those patients by comprehensive nutritional assessment. But the mechanism of this nutritional disturbance remains unclear. We anticipated that cytokines contributed to the nutritional disturbance. To elucidate this mechanism we measured the productions of interleukin-1 (IL-1) and tumor necrosis factor (TNF) by peripheral blood monocytes, and correlated them with nutritional parameters in those patients. These cytokines had been reported to mediate metabolic alterations in inflammatory process. Subjects were 45 patients with bacteriologically confirmed pulmonary tuberculosis and their controls matched by age and sex. Adherent monocyte at 0.5 x 10(6)/ml were stimulated by lipopolysaccharide (LPS), and the culture supernatant was measured by ELISA for IL-1 and TNF. In order to assess nutritional status we measured serum albumin, transferrin, prealbumin, retinol binding protein, branched chain amino acid (BCAA)/aromatic amino acid (AAA) ratio as amino acid imbalance index, % ideal body weight (%IBW), % arm muscle circumference (% AMC) as muscle mass index, % triceps skin fold thickness (% TSF), as fat store index. The results were as follows: (1) Patients with active pulmonary tuberculosis were confirmed to be malnourished in visceral proteins, plasma amino acid, and anthropometric indices. (2) In patients with moderate or mild nutritional depletion the production of IL-1 and TNF was higher than that in healthy controls, and significantly correlated inversely with the nutritional parameters. (3) In patients with severe nutritional depletion the production of IL-1 and TNF was lower than that in healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acids↗
Efficient method of haemoglobin F enrichment in adult haemolysate for determination of the gamma-chain isoforms by high-performance liquid chromatography.
An alkali denaturation procedure was developed for the efficient enrichment of haemoglobin F (Hb F) in human adult haemolysate. In contrast to the previous procedures, the method is readily applicable to small amounts of blood containing less than 1% of Hb F, providing reproducibly a sufficient level of Hb F (at least 11%) to allow an accurate high-performance liquid chromatographic determination of the three gamma-chain isoforms. Further enrichment was possible by combination with CM-Sephadex chromatography.
Adult↗
Analysis of clonal evolution in a tumor consisting of pSV2neo-transfected mouse fibrosarcoma clones.
The process of clonal evolution was analyzed in a line of methylcholanthrene-induced mouse fibrosarcomas. The tumor cells were transfected with pSV2neo gene and 22 clones were randomly isolated. Genetically tagged clones were mixed and inoculated into syngeneic mice. Southern blot analysis revealed that one of the clones, no. 11, dominated both in tumors in situ and in lung metastatic nodules. No. 11 clone and other clones were similar in growth rates in vitro and in vivo, in spontaneous and experimental metastatic abilities, in immunogenicity, and in the capacity of intercellular communication in vitro. Although no. 11 clone overgrew other clones in vivo, this was not the case when clones were mixed and maintained in vitro. We conclude that clonal interactions in vivo may be responsible for the dominance of no. 11 clone in the tumor. It is likely that the preferential metastasis of no. 11 clone to the lung may be a simple reflection of the proliferative advantage of the dominant clone in the tumor in situ.
Animals↗
A simple procedure for determination of the dead time of a stopped-flow instrument.
The reducing reaction of 2,6-dichlorophenolindophenol by L-ascorbic acid was used to determine the dead time of a stopped-flow instrument. Because this reaction is irreversible, the dead time could be determined by a simple graphical analysis. The dead time values determined by the present method were comparable to those by other methods previously reported.
2,6-Dichloroindophenol↗
[Nutritional assessment of chronic pulmonary emphysema and the significant relation of malnutrition to pulmonary function and respiratory muscle function].
We assessed nutritional status in 30 patients with pulmonary emphysema and 60 healthy controls. The relationship between nutritional status, pulmonary function and respiratory muscle function was also studied. Anthropometric measures, visceral proteins such as PA and RPB, and the Fischer ratio (BCAA/AAA), an index of imbalance of amino acids were significantly lower in the patients. The incidence of moderately malnourished patients with less than 80% of IBW was 40%. The incidence of hyporetinol-binding protein was 40%. 48% of the patients were found to show an amino acid imbalance. These findings suggested that protein-energy malnutrition in association with amino acid imbalance occurred commonly in patients with pulmonary emphysema. FEV1% correlated significantly with some anthropometric indices and the Fischer ratio. Respiratory muscle function, assessed by P1 max, correlated significantly with some anthropometric indices and grasp strength. These results suggested that the degree of airway obstruction and respiratory muscle function was associated with malnutrition characterized by the reduction of the Fischer ratio.
Adult↗
[Changes in content of excitatory amino acids in the brain and cerebrospinal fluid].
Recently epilepsy is analysed on terms of two different conditions, seizure susceptibility and seizure induction. Much attention has been paid to excitatory amino acids in these conditions. An examination was made of changes of glutamate and aspartate in the brain and cerebrospinal fluid (CSF) in a cat amygdaloid kindling model so as to determine whether excitatory amino acids are possibly involved in seizure susceptibility and seizure induction. Twenty crossbred adult cats were divided into four groups: a sham operation group (Sh) as the control, just after stage 4 seizure group (S4), just after stage 6 seizure group (S6), and stage 6 group 2 weeks after the last stimulation (S6-2W). CSF, blood and 13 individual brain regions were taken at 9 + 4 degrees C, and their glutamate and aspartate contents were measured by high performance liquid chromatography (HPLC). Glutamate concentration was significantly higher in the S6 group than in the Sh group in CSF and less in the S6 group than in the Sh group in the left and right amygdala, hippocampus and piriform cortex. No aspartate could be detected in the CSF of any group, nor did it change significantly in the blood or brain. Based on the above results, the content and release of glutamate and aspartate apparently do not change in seizure susceptibility and glutamate is released from kindled tissues in seizure induction, thus showing it to be involved in seizure induction in a cat amygdaloid kindling.
Animals↗
Overexpression and amplification of the c-myc gene in mouse tumors induced by chemicals and radiations.
We examined expression of the c-myc gene by the dot blot hybridization of total cellular RNA from mouse primary tumors induced by chemicals and radiations. Expression of the c-myc gene was found to be elevated in 69 cases among 177 independently induced tumors of 12 different types. DNA from tumors overexpressing the myc gene was analyzed by Southern blotting. No case of rearrangement was detected. However, amplification of the c-myc gene was found in 7 cases of primary sarcomas. These included 4 cases out of 24 methylcholanthrene-induced sarcomas and 3 cases out of 7 alpha-tocopherol-induced sarcomas. We also analyzed 8 cases of sarcomas induced by radiations, but could not find changes in the gene structure of the c-myc gene. Thus, our data indicate tumor type specificity and agent specificity of c-myc gene amplification.
Animals↗
Temporal changes of plasma erythropoietin level in hypobaric hypoxic mice and the influence of an altered blood oxygen affinity.
Temporal changes of plasma erythropoietin (Epo) in mice exposed to hypobaric hypoxia were studied by a fetal mouse liver cell culture method. Since a colony formation inhibitory activity was found in the mouse plasma, thirteen pretreatment procedures for bioassay were compared and the procedure of shaking with chloroform followed by dialysis was concluded to be the best. When normal mice (P50 = 40.4 +/- 2.2 Torr) were exposed to hypoxia of 350 Torr, the plasma Epo level was elevated, with peak at the 2nd to 3rd day, and afterwards declined gradually. On the contrary, cyanated mice (P50 = 30.1 +/- 1.5 Torr) showed much less of the Epo response when exposed to 350 Torr. Under 200 Torr hypoxia, both mice exhibited a similar and remarkable extent of the response. These results suggest that the renal Epo-producing tissue or its oxygen-sensing system is less hypoxic in cyanated mice than in normal mice under 350 Torr, and that the physiologically optimal oxygen affinity of blood is variable depending on hypoxic degrees. The fact that the inhibitory activity showed an inverse temporal change to that of Epo, suggested a possible important role of this activity in the regulation of erythropoiesis under hypoxia.
Administration, Oral↗
Hb Hope, beta 136(H14)Gly----Asp, in a diabetic Japanese female and its functional characterization.
A beta-variant hemoglobin, first misjudged as a marked elevation of Hb A1, was found in a 68-year-old Japanese female with diabetes mellitus. This hemoglobin was isolated by Bio-Rex 70 chromatography combined with chromatofocusing, and was found to be Hb Hope, beta 136(H14)Gly----Asp, by classical and high performance liquid chromatographic peptide mapping techniques. Intrinsic oxygen affinity of this hemoglobin was approximately one-third as compared with that of Hb A0. This property was still observed in the constituent beta subunits isolated. Effects of such allosteric effectors as H+ (at a fixed concentration of Cl-), anion (Cl-), 2,3-diphosphoglycerate and carbon dioxide were more or less depressed. Among others, a marked reduction in the carbamate effect should be noted in a structural interpretation of the functional modifications. Subunit cooperativity, on the contrary, was not different from that in Hb A0 (n = 2.8-2.9). Explanation of these altered functions were attempted on the basis of the altered structure. The reduced stability of Hb Hope is also described.
Aged↗