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Biomedical subjects

G Chalevelakis

Publications and source records attributed to G Chalevelakis.

34 records · Page 2Linked to original sources
PubMed1986

Adverse effect of cis-diamminedichloroplatinum II (CDDP) on porphyrin metabolism in man.

The possible effect of cisplatin on porphyrin metabolism was studied in 25 patients with various malignancies treated with high-dose cis-diamminedichloroplatinum. Haematocrit, red blood cells, haemoglobin, white blood cells, platelets and reticulocytes together with coproporphyrin and protoporphyrin in red blood cells were determined before each course of chemotherapy in all patients. In addition, coproporphyrin, uroporphyrin, delta-aminolevulinic acid, and porphobilinogen were determined in the urine just before and 24 h after each course of treatment. Cisplatin administration was followed by a significant suppression of coproporphyrin and protoporphyrin in red blood cells and coproporphyrin, uroporphyrin, delta-aminolevulinic acid and porphobilinogen in urine. The changes observed paralleled similar changes in haematocrit, red blood cells and haemoglobin, strongly suggesting that cisplatin-induced anaemia may be due to a blocking effect of the drug affecting one or more enzymatic steps in the biosynthesis of porphyrins and haem. A moderate fall in the white blood cell count and a mild fall in platelets together with a steady increase of reticulocytes were also observed during treatment.

Adolescent↗
PubMed1986

Some parameters of haem synthesis in dialysed and non-dialysed uraemic patients.

Some parameters of haem synthesis were estimated in 60 uraemic patients (30 non-dialysed, 30 dialysed) and in 30 matched controls. Serum delta-aminolaevulinic acid and erythrocyte coproporphyrin and protoprophyrin were found significantly higher in the non-dialysed uraemics than in the controls. Erythrocyte delta-aminolaevulinic acid dehydrase (ALA-D) activity was 498 +/- 174 mumol/h.l in the non-dialysed patients, 321 +/- 146 in the dialysed (just before haemodialysis) and 833 +/- 281 in the healthy controls, the differences between these groups all being statistically significant (p less than 0.001). After haemodialysis the enzymic activity in the dialysed group increased significantly (380 +/- 167, p less than 0.001), but remained lower than normal (p less than 0.001). A similar pattern - although with less statistical significance of the differences between groups - was observed concerning erythrocyte uroporphyrinogen I synthase activity. Incubation of normal erythrocytes with uraemic plasma resulted in a considerable decrease of their ALA-D activity (from 830 +/- 263 to 616 +/- 126) while incubation of uraemic erythrocytes with normal plasma increased their ALA-D (from 384 +/- 139 to 494 +/- 77). Addition of zinc in the haemolysate caused a similar induction of ALA-D in both controls and uraemics. The zinc-induced uraemic ALA-D practically reached normal levels. The mechanism of enzymic depression and the possible role of elevated delta-aminolaevulinic acid concentrations (to which depressed ALA-D activity considerably contributes) in the pathogenesis of the neurologic manifestations of uraemia, are discussed.

Erythrocytes↗
PubMed1986

Effect of uremic plasma on mouse liver delta-aminolevulinic acid synthetase activity.

delta-Aminolevulinic acid (delta-ALA) synthetase in mouse liver homogenate was significantly (p less than 0.001) higher in the presence of uremic compared with normal plasma, the ratio of the two values being 1.36 +/- 0.24 in 30 paired experiments. This effect does not seem to be due to increased concentrations of urea or creatinine nor to any possible dialyzable substances. Its relationship to the retention of an inducing factor or decreased production of erythropoietin in uremic patients is discussed. A possible inhibitory effect of erythropoietin on liver delta-ALA synthetase is suggested.

5-Aminolevulinate Synthetase↗
PubMed1984

Rapid proteolysis of puromycyl peptides in non-thalassaemic and thalassaemic erythroid cells.

The proteolytic degradation of labelled pyromycyl polypeptides was investigated in human intact erythroid cells derived from the bone marrow of eight non-thalassaemic patients and the peripheral blood of eleven thalassaemics (eight splenectomized beta thalassaemia heterozygotes and three sickle-cell beta thalassaemics). These abnormal polypeptides are rapidly degraded to soluble trichloroacetic-acid (TCA) fragments with a half-life of 12 min both in bone marrow and peripheral blood. This comes very close to the half-life reported for the puromycyl peptide degradative system in rabbit reticulocytes (15 min). The relationship of the present proteolytic system to the ATP-dependent one, described in rabbit reticulocytes, and to that responsible for the free alpha-chain degradation in beta thalassaemia is discussed.

Bone Marrow Cells↗
PubMed1984

Screening for thalassaemia and/or iron deficiency: evaluation of some discrimination functions.

The number concentration of erythrocytes in blood (RBC) and the discrimination functions MCV/RBC, (MCV)2 X MCH, DF = (MCV/fl) - (RBC/10(12).1(-1] - (8.1 X Hb mmol.1(-1] - 3.4 have been advocated as useful methods in screening programmes for thalassaemia. In the present work we attempted to estimate the value of each of these methods in screening programmes for thalassaemia and/or iron deficiency and in differentiating between these two conditions. One hundred and twenty-six subjects suffering either from iron deficiency anaemia or heterozygous beta, delta beta, 'silent' beta and alpha 1 thalassaemia were classified by using these methods. Forty healthy subjects served as controls. The RBC was greater than 5.5 X 10(12)1(-1) in 80% of the cases, the three discrimination functions were 'positive' in 91%, 94% and 92% respectively. MCV/RBC and (MCV)2 X MCH separated successfully the subjects with microcytic anaemia (heterozygous thalassaemia and iron deficiency) from normal controls. On the other hand the DF turned out to be more satisfactory than RBC in discriminating heterozygous thalassaemia from iron deficiency anaemia. Thus in population screening for thalassaemia either MCV/RBC or (MCV)2 X MCH ought to be used first and then the DF.

Adult↗
PubMed1983

Correlation of haematological, electron microscopic and cytogenetic findings in 20 patients with preleukaemia.

A combined haematological, ultrastructural and chromosomal study was made in 20 patients with preleukaemia. There was evidence of specific correlations between (a) Hb F levels and pancytopenia or profound anaemia, (b) chromosomal and electron microscopic findings and (c) thrombocytosis and ringed sideroblasts. The above findings might be of importance in identifying subgroups of preleukaemic patients with different prognosis.

Aged↗
PubMed1979

Globin chain synthesis in sickle beta-thalassaemic bone marrow and reticulocytes.

Globin chain synthesis was studied in reticulocytes and bone marrow erythroid precursors in four sickle beta-thalassaemic Greek patients. Significant globin chain imbalance was found in reticulocytes (alpha/gamma + beta A + beta S = 2.20 +/- SD 0.16) and bone marrow (alpha/gamma + beta A + beta S = 1.58 +/- SD 0.11) after two hours' incubation. There was evidence of contamination of the gamma, beta A, and, to a lesser extent, of the beta S chain by non-haem proteins. The contamination was more obvious in chromatograms obtained from whole cell bone marrow samples and could partially explain the lower alpha/non-alpha ratio found in bone marrow.

Anemia, Sickle Cell↗
PubMed1977

A new approach to the diagnosis of beta-thalassaemia.

By use of isoelectric focusing in polyacrylamide gel rods we were able to detect traces of HbA (approx. 1%) as a sharp and discrete band. By overloading the gel considerable amounts of HbA (slightly contaminated with HbF) could be detected and isolated. The focused HbA was retrieved from the gels, separated from the carrier-ampholytes and concentrated by a one-step electrophoresis technique. With 3H-leuci ne-labelled haemolysates, after globin chain separation on CM-cellulose, an increase of the beta-chain counts relative to gamma-chain counts was obtained. The study of two cases of high HbF homozygous beta-thalassaemia has demonstrated that this technique may be a valuable tool in detecting minute amounts of HbA mainly in high HbF beta-thalassaemias.

Electrophoresis, Polyacrylamide Gel↗
PubMed1977

Erythrocyte delta-aminolaevulinic acid dehydratase, urinary porphyrins and porphyrin precursors in iron deficiency anaemia.

In 20 iron deficient patients and 21 normal controls the activity of the enzyme delta-ALA dehydratase of erythrocytes was assayed. In addition the urine porphyrins and porphyrin precursor excretions were measured. It was found that in sideropenic patients the erythrocyte delta-ALA dehydratase activity was almost constantly higher than in normals; the difference of the mean values being statistically significant (p less than 0.005). A significant diminution of delta-ALA (p less than 0.0025) urine excretion was observed, whereas the urine excretion of PBG, CP and UP was found within the normal limits. The results are compared to those reported by other authors.

Anemia, Hypochromic↗
PubMed1976

Globin synthesis in normal human bone marrow.

Globin synthesis has been studied by in vitro labelling with radioactive amino acids in 60 normal human bone-marrow samples. Under the conditions routinely used to fractionate alpha and beta chains by chromatography alpha/beta production ratios ranging from 0.5 to 1.0 were obtained, depending on the method of sample treatment. This variation was due entirely to the presence of non-haem proteins derived from white cells which chromagraphy with globin on CM-cellulose. Purification of globin on Sephadex G100 and fractionation of alpha and beta globin chains by a modified chromatographic system resulted in alpha/beta ratios of unity. The relevance of these findings to the study of marrows in which there is unbalanced globin chain production is discussed.

Blood Proteins↗
PubMed1975

Imbalanced globin chain synthesis in heterozygous beta-thalassemic bone marrow.

Globin synthesis was studied in the bone marrow of seven heterozygous beta-thalassemic subjects. We found evidence of significant imbalance of alpha- and beta-chain production particularly at short times of incubation. There was a progressive decrease in alpha/beta-chain production ratio with increasing incubation time which was due to a decreased rate of net alpha-chain production, indicating that a large proportion of the newly synthesized alpha chains are degraded, particularly in bone marrow, within a few minutes of synthesis, leading to relatively low alpha/beta ratios if these are measured solely at incubation times greater than 10 min. The significant degradation of excess alpha chains explains why inclusion body formation and ineffective erythropoiesis, notable in beta-thalassemia homozygotes where there is gross chain imbalance, are not observed to any marked degree in heterozygotes.

Bone Marrow↗
PubMedDate not supplied

Estimation of glycated fetal hemoglobin in normal cord blood by isoelectric focusing. Correlation with maternal glycated hemoglobin and birth weight.

Glycated fractions of hemoglobin F and A (F1, A1c) were measured simultaneously in cord and maternal blood, respectively, in 109 normal women at delivery using an isoelectric focusing, method in polyacrylamide gel plates. Cord blood hemoglobin F1 values (mean +/- SD) were 5.92 +/- 1.09% and maternal blood hemoglobin A1c values were 6.51 +/- 0.92%. The difference was statistically highly significant (p less than 0.001) and their values were also significantly correlated (p less than 0.001). Moreover, both values were also well correlated with those of maternal blood glucose (p less than 0.01), actual birth weight (p less than 0.01) and birth weight ratio (p less than 0.01). It is concluded that hemoglobin F1 can be successfully separated and measured by isoelectric focusing. However HbF1 estimation seems to have no obvious advantages against the maternal HbA1c measurement as an index of fetal exposure to glucose during the last weeks of pregnancy.

Adolescent↗