Protein-energy malnutrition and anemia in Kivu.

Protein-energy malnutrition in Kivu is associated with a discrete normocytic, normochromic anemia. An attempt to define the physiopathology of this anemia disclosed the following results. As compared with local controls, both iron and total iron binding capacity were low, but with siderophilin saturation and sideroblast counts either normal or elevated; serum and erythrocyte folate was normal, plasma vitamin B12 was normal or elevated, and serum ascorbic acid was normal or elevated. The riboflavin nutritional status was normal. During refeeding, iron and riboflavin deficiencies became apparent. Characteristic findings on admission were the presence of giant erythroblasts and a diminished erythrocyte survival time implicated to an intracorpuscular hemolysis. Two results from the present study could contribute to explanation for the aforementioned abnormalities: low plasma vitamin E levels and, perhaps more importantly, low plasma selenium levels. In conclusion, the anemia of protein-energy malnutrition, as observed in Kivu, is a classifiable nonadaptive anemia that cannot be explained by isolated iron or vitamin deficiencies and whose physiopathology is distinct from that of the anemia of chronic disorders. It is suggested that a selenium deficiency may play an important role in the pathogenesis of this anemia.

Erythrocyte glycolysis in protein-energy malnutrition.

Erythrocyte glycolysis has been studied in the anaemia associated with protein-energy malnutrition (PEM) in Kivu. Several results were compatible with a lowering of the mean age of the erythrocyte population, notably raised levels of glucose-6-phosphate, hexokinase, Na+-K+- adenosinetriphosphatases and potassium, and low sodium concentration. Non-significant differences were observed for glucose utilization, lactate formation, and for concentrations of fructose-6-phosphate, fructose-1,6-diphosphate, adenosine diphosphate and pyruvate kinase; there was no gross disturbance of cation transport. The level of adenosine triphosphate was slightly decreased and that of 2,3-bisphosphoglycerate was not elevated, in spite of anaemia. The latter could not be explained by an instability of this metabolite. It is concluded that slight erythrocyte glycolytic abnormalities may occur in the anaemia of Kivu PEM, but that they are not the main cause of the haemolysis observed in this syndrome.

[Erythrocyte metabolism in vitamin D deficiency rickets]. / Métabolisme érythrocytaire dans le rachitisme carentiel.

In an attempt to explain the hemolysis observed in vitamin D deficiency rickets in the infant, we studied erythrocytic glycolysis, the level of ATP and some of the key enzymes of the glycolytic pathway. This study was performed in one group of vitamin D deficient infants and in one control group. The values obtained in these two groups did not differ significantly. In the absence of a defect in the glycolytic pathway, we suggest that an anomaly exists in the red cell membrane of these patients.

Marasmic kwashiorkor anemia. III. Hemoglobin oxygen affinity.

Oxygen-hemoglobin dissociation curve, 2,3-diphosphoglycerate (2,3-DPG), and adenosine triphosphate (ATP) have been studied in marasmic kwashiorkor before re-feeding, after re-feeding, and in control children. P 50 and 2,3-DPG level are normal on admission, but high after re-feeding. Patients studied on admission were separated into 2 groups according to whether they presented active erythropoiesis (group I) or erythroblastopenia (group II). In group I, the sum 2,3-DPG + ATP correlates with the hemoglobin level. In group II, the sum 2,3-DPG + ATP correlates with the blood pH but not with the hemolobin level. It is suggested that marasmic kwashirokor anemia is an adaptation to a reduced metabolic activity. The hematological picture could proceed in 2 stages in this disease. In a first stage, the erythropoiesis is normal or increased because of the existence of a decreased red cell life span; a low hemoglobin level is observed, but there is no apparent hypoxia. At a more advanced stage of the disease, the tissue metabolism falls dramatically, the erythropoiesis is no loner stimulated, and the erythrocyte volume decreases notably.

Protein kinase C deficiency in juvenile chronic myeloid leukemia: a case report.

Protein kinase C activity was assayed in morphologically differentiated and undifferentiated myeloid cells of a 13-month-old girl with chronic myeloid leukemia. A reduced protein kinase C activity was seen in the morphologically differentiated neutrophils, while the activity in the leukemic cells was higher to that of normal neutrophils from control subjects.

Fluctuation of the biochemiluminescence from PMN leukocytes in a family with a high prevalence of severe periodontitis.

Rapidly progressive periodontal disease was found in three patients belonging to three different generations of the same family. Beyond the clinical inspection, blood examination allowed measurements of the luminol enhanced biochemiluminescence from the circulating PMN leukocytes. Abnormally low values were recorded in the affected individuals (75, 84 and 138 mVolts per 10(6) cells) whereas a sample of healthy individuals exhibited photonic values from 240 up to 910 mVolts per 10(6) cells. These abnormal values, however, were not constantly recorded. They gave way to higher PMN activity indices after the patients had been treated either by antibiotics, scaling, debridement or classical pocket cleaning.

Inhibition of human polymorphonuclear leukocytes phagocytosis and protein-kinase-C activity by low pH concentrations.

PMN leukocytes from circulating blood, were investigated using the following parameters: chemiluminescence, superoxide generation, exocytic degranulation, lactoferrin, myeloperoxydase and protein-kinase-C activities. The results did not allow to point out any significative discrepancy between samples collected from either patients suffering of periodontal disease or healthy individuals. However, the phagocytic ability (as measured by light emission and superoxide production) was found to be severely inhibited in both instances, when PMN leukocytes were incubated in the presence of succinic acid. Similarly, protein-kinase-C activity in these cells, collapsed when the pH was brought down to 5.5. These data and the available literature indicate that pH decrease as well as succinic acid release in the crevicular fluid, may play a role in the pathogeny of chronic periodontitis in adults.

Anaerobes and short-chain fatty acids in crevicular fluid from adults with chronic periodontitis.

Pathogeny of adult chronic periodontitis is still unclear. Bacteriological and chemical analysis of crevicular fluid have shown, in active sites of the disease, a simultaneous presence of anaerobes and their major by-product: short-chain fatty acids. The last can decrease "in vitro" the neutrophil intracellular pH, whenever these cells are incubated in an acid medium. Clinical investigations are scarce which hold out data useful to attempt verifying this possible physiopathological mechanism. This work shows the presence of anaerobes in the active periodontal pockets, together with the presence of short-chain fatty acids likely to reach a concentration level comparable to that used for inhibiting neutrophils "in vitro". Forthcoming studies should investigate about a possible intracellular pH drop in the neutrophils and other cells of the inflamed periodontium.

Thymidine kinase and thymidine phosphorylase activities in various types of leukaemia and lymphoma.

Thymidine kinase (TK) isoenzymes and thymidine phosphorylase (TP) activities have been measured in peripheral mononuclear cells of patients with acute lymphoblastic and monoblastic leukaemia or B-chronic lymphocytic leukaemia, as well as in normal subjects, and also in lymph node cells from patients with non-Hodgkin's lymphoma, with Hodgkin's disease and with benign adenopathies. TK1 isoenzyme activity was highest in acute lymphoblastic leukaemia and in centroblastic lymphoma. Then in progressively decreasing order appeared the Hodgkin's disease values, the centroblastic centrocytic lymphoma values and the benign reactive lymph node cell values. When compared to normal blood mononuclear cells, TP was greatly decreased in acute lymphoblastic leukaemia and slightly but significantly decreased in chronic leukaemia. Monoblastic cells exhibited a unique enzyme pattern; moderately increased TK1 activity and high TP activity. Our results suggest that both enzymes are indicative of the maturation status of leukaemic cells from B lineage. They demonstrate that in lymph node cells, TK1 reflects the proliferative status of both malignant and non-malignant cells and that in monoblastic cells the synthesis of dTMP through de novo synthesis is favoured.

Enzymes of purine metabolism in B-chronic lymphocytic leukemia.

In order to study if enzymes of purine metabolism could be used as cell markers in B-chronic lymphocytic leukemia (B-CLL), the activities of adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'-nucleotidase (5'N) were repeatedly measured in blood mononuclear cells from B-CLL patients and were compared to those obtained in normal controls. Enzyme activities in patients were also compared to other biological parameters indicative of B-CLL to activities of ADA and PNP in erythrocytes. Results show that B-leukemic cells display abnormal enzyme patterns: subnormal ADA activity is characteristic; 5'N activity is depressed in 60% of the cases but increased in 15%. An inverse relationship between PNP activity and corresponding lymphocytosis is observed in leukemic but not in normal cells. The enzymatic anomalies seem to be linked to the presence of an unusual peripheral lymphocytic population, induced by the leukemic process. Indeed, ADA and PNP are not abnormal in erythrocytes. In untreated nonevolutive patients, the enzyme profile tends to remain stable throughout the course of the illness; normalization of enzyme patterns in treated patients occurs only when therapy induces improvement in T and B cell distribution.

Abolition of herpes simplex cytopathic effect after treatment with peroxidase generated hypothiocyanite.

HSV1 suspensions were pre-incubated in a lactoperoxidase thiocyanate oxidizing system before inoculation in MRC5 fibroblast cultures. This pre-treatment could either delay or even abolish the HSV1 cytopathic potentiality. The effect was found to be time-dependent.

Deoxythymidine and deoxycytidine incorporation into DNA in B leukemic cells.

Measurements of radioactive DNA after incubation of normal and B leukemic peripheral mononuclear cells, from c-ALL and CLL with labeled deoxythymidine (dTh) and deoxycytidine (dCt) showed that for dTh, incorporation into DNA was similar for normal and c-ALL cells but lower in B-CLL cells and that for dCt, incorporation was highest in c-ALL and lowest in CLL cells. These results contrast with those of dTh and dCt kinase activities; the former has been previously found elevated in c-ALL cells, and the latter is found, in the present study, similar in the three groups tested.

[Iron metabolism during proteoenergetic malnutrition in children]. / Aspects du métabolisme du fer dans la malnutrition protéo-énergétique de l'enfant.

The iron stores are normal in marasmic kwashiorkor in kivu, but they notably decrease on re-feeding. On admission, the total iron binding capacity depends not only on the severity of the protein depletion but also on the iron stores. There exists an abnormality of the iron release from the stores; this cannot be attributed to the hypotransferrinemia or to the hypoceruloplasminemia, which are too moderate, nor to an ascorbic acid deficiency, but possibly to the inflammatory state which is a feature of kwashiorkor. The iron deficiency which occurs on re-feeding is not explained by abnormalities of iron absorption or by increased iron loss, but by the raised requirement for iron. Parental iron treatment alone is required to normalise the packed cell volume and the red cell volume after re-feeding.

Clonal origin of a T cell lymphoproliferative malignancy.

A woman with a T cell lymphoproliferative malignacy and heterozhgosity at the X chromosome-linked locus for glucose-6-phosphate dehydrogenase (G-6PD) isoenzymes was studied to find the clonal origin of her circulating neoplastic T cells. The red blood cells, polymorphonuclear cells, whole mononuclear cells, and T cell-depleted mononuclear cells contained both A and B isoenzymes of G-6-PD. In contrast, the tumor cells, separated by using their capacity to form rosettes with sheep red blood cells, contained only the B isoenzyme of G-6-PD. This observation strongly suggests the monoclonality of this T cell malignancy.