Immediate-early, transient induction of the interleukin-1 beta gene in mouse spleen macrophages by ionizing radiation.

In murine spleen cells, x ray irradiation induces the expression of the IL-1 beta gene at multiple phases of the peak time. We analyzed the immediate-early phase of IL-1 beta mRNA accumulation. To determine the lineage of cells that showed the immediate response to irradiation, normal spleen cells were analyzed by Northern blotting and in situ hybridization after separation by magnetic antibodies against specific cell-surface antigens. Although most of the spleen macrophages continuously expressed a low level of IL-1 beta mRNA, a portion of the macrophage population transiently accumulated large amounts of IL-1 beta message immediately after irradiation. A macrophage-like leukemia cell line that resembles these inducible macrophages was identified. A similar immediate-early and transient increase in the IL-1 beta mRNA level occurred when cultured spleen cells were irradiated with a low dose (3 Gy) of x rays. In contrast, the x ray-inducible expression of the IL-1 beta gene was immediate and continuous, not transient, in spleen cells from whole-body irradiated mice. Results of the run-on transcription assay and the determination of the decrease in the message using cultured spleen and macrophage-like leukemia cells indicated that x ray irradiation appears to activate the transcription of the IL-1 beta gene and partially stabilize the message. The results show that the x ray-induced immediate-early accumulation of IL-1 beta mRNA is regulated at both the transcriptional and post-transcriptional levels in an as yet unidentified population of spleen macrophages.

Evidence of trapped red cells in the brain of rhesus monkey infected with Plasmodium knowlesi.

59Fe-labelled normal red cells and 51Cr-labelled P. knowlesi infected red cells were used as tracers for a study on the trapped red cells in the brain of rhesus monkeys infected with P. knowlesi. After instantaneous injection into a common carotid artery, blood was sampled from both of the internal jugular veins at various intervals. Results in 6 experiments on 3 infected monkeys showed that about 17% of infected red cells given was trapped in the capillaries of the brain of the infected monkeys. The remainder of the infected red cells travelled on the same flow rate as the normal red cells. As the volume for the flow of the former was less than that of the latter, the mean transit time of the infected red cells (-ty) was therefore shorter than that of the normal red cells (-th). The mean difference in volume was estimated to be 3.4% in the present study. These findings indicated that some of the P. knowlesi infected red cells were trapped in capillaries of the brains of monkeys infected with P. knowlesi.

Serum transcobalamin II levels in patients with malaria infection.

Serum transcobalamin II (TCII) levels were determined in 56 patients with P. falciparum malaria infection. They were divided into 3 groups: severe (malarial parasite > 5% or patients with cerebral malaria or renal insufficiency), moderate (1-5% infection without complications) and mild (1% infection). Elevated serum TCII values were found only in patients with severe malaria infection. These values correlated directly with parasitemia, blood urea nitrogen and creatinine, but were not correlated with alkaline phosphatase. As 17 patients with azotemia had elevated serum TCII levels while other 3 patients with normal BUN and creatinine concentrations had serum TCII levels within the normal limits. These findings indicated that malarial patients with renal insufficiency had increased serum TCII. A possible mechanism is the reduced TCII-B12 that filtered through the glomeruli due to the reduced renal blood flow with the decreased its uptake by proximal tubular cells resulting in the decreased degradation of TCII by the tubular lysosomal enzymes. Determination of serum TCII level may be used as an indicator of renal function in malarial patients with renal insufficiency.

Factors influencing blood viscosity: adult and newborn blood analysis.

Our finding of a decrease in blood viscosity in newborn infants compared with adults leads to analysis of this change by measuring blood viscosity, plasma fibrinogen concentration, plasma viscosity and mean corpuscular volume (MCV) of 24 adults and 16 newborn infants. Plasma proteins in newborn infants are synthesized to a lesser extent than in adults, therefore plasma fibrinogen concentration of newborn infants is less than that of adults. This causes decreased blood viscosity in newborn infants compared with adults. Secondly plasma viscosity of newborn infants is also less than that of adults. In the same situation this causes a decrease in blood viscosity in newborn. Thirdly. MCV of newborn infants is greater than that of adults because of young red cells. There is a negative correlation between blood viscosity and MCV. High MCV in newborns leads to low blood viscosity in newborn infants, compared with adults.

Red cell acetylcholinesterase activity in Plasmodium falciparum malaria.

Red cell ACHE activity was determined in 19 patients with P. falciparum malaria, 13 patients during convalescence as well as in 6 normal subjects. There was no significant difference between the mean values of ACHE in red cells of these 3 groups. After separation these blood samples into 2 portions by centrifugation in 5% Ficoll solution, the parasitized red cells in the lower portion which are mostly ring forms contained the same amount of ACHE activity as those of the normal subjects and the non-parasitized red cells. However, the parasitized red cells in the upper portion which contained predominantly mature asexual forms revealed a significantly higher ACHE activity than those of the normal red cells. There was also a reverse relationship between red cell ACHE activity and the parasitaemia from this portion of blood sample. These findings indicated that although malarial parasite invaded and caused the red cell membrane damage, it did not inactivate ACHE. It may be concluded that ACHE was not responsible for the anaemia and excessive erythrocyte destruction in patients with P. falciparum malaria.

Studies on the effect of folic acid supplement on folate and vitamin B12 status in children.

The effect of folic acid supplement (15 mg folic acid per day) for 5 weeks was studied on a group of 5 children aged 8-12 years who were admitted to hospital. The result was compared to a control group of 5 children who were given a placebo. After supplementation, both serum and red cell folate levels in the experimental group significantly increased, i.e., 15 fold (82.0 ng/ml) and 4 fold (880 ng/ml), respectively. Serum UFBP decreased considerably while TFBP showed no significant alteration which resulted in the elevation of the % saturation to its maximum value. These findings indicated that the supplementary folic acid not only increased both serum and red cell folate levels and saturated nearly all serum UFBP but also elevated the % saturation markedly. There were no definite changes of serum vitamin B12, UBBC, TBBC and TC levels of the experimental group from those of the control group. There were slightly but not significantly increased blood haemoglobin and haematocrit levels in both groups of children. This indicated that folic acid supplement had no definite effect on vitamin B12 and haematological findings in this study.

Serum vitamin B 12 and folic acid levels in patients with fasciolopsiasis.

Serum vitamin B12, serum and red cell folate concentrations and vitamin B12 absorption were studied in 100 patients with fasciolopsiasis. A mean value of serum vitamin B12 level in the patient group was found to be significantly lower than that of normal subjects and 14% of these patients had serum vitamin B12 level less than 100 pg/ml. Serum UBBC and TBBC levels in the patients were significantly higher than those of the normal subjects. Serum TCI and TCIII increased significantly while TCII decreased. Vitamin B12 absorption was found to be impaired in 3 of 9 patients studied. There was no relationship seen between serum vitamin B12 level and vitamin B12 absorption. The mean values of serum folate and red cell folate levels in the patient group were significantly lower than those of normal subjects. Fifteen of 100 patients (15%) had serum folate level less than 3 ng/ml, while all of them had red cell folate higher than 100 ng/ml. Serum folic acid binding protein levels (FABP) in these patients, were not significantly different from those of normal subjects.

Serum folate and folic acid binding proteins in iron deficiency anaemia.

Serum and red cell folate and folic acid binding protein (FABP) concentrations were determined on 20 iron deficiency anaemic children of both sexes aged 6--12 years. All cases had haemoglobin level less than 12 gm% or haematocrit less than 36% with low serum iron and elevated unsaturated iron binding capacity. Serum folate levels in the anaemic group was not significantly different from that of normal subjects while red cell folate level was significantly lower in the anaemic group. However, all cases had red cell folate levels higher than 100 ng/ml. There was a direct relationship between the haemoglobin concentration and serum folate level. Serum FABP level in the anaemic group was found to be significantly higher than that of normal subjects and showed no correlation with haemoglobin, haematocrit, serum or red cell folate levels. The significance of elevated serum FABP was discussed.

Persistently elevated serum transcobalamin II in a patient with cerebral malaria and typhus infections.

A 25-year-old man presented with a history of fever, chills and vomiting for three days. The parasite count was 207 ring-forms of P. falciparum per 1000 red cells. He developed hemoglobinuria and excreted hemoglobin in the urine 0.20-0.30 g/dl for 14 days during admission. Many blood transfusions were administered for correcting anemia. Although the malarial parasites disappeared one week after anti-malarial therapy, however, the fever and hemoglobinuria persisted. The Weil-Felix reaction OXK was positive with a titre of 1:40 on admission and increased to 1:160 on the second week. Chloramphenical and prednisolone were given for treatment of typhus fever and all symptoms subsided. Serum TCII levels were found to be increased and persisted high during the hemoglobinuria. The clearance of TCII was lower and increased relatively slowly to the normal level on day 30. On the other hand, TCII excretion in the urine was found to be increased during hemoglobinuria. These findings indicate that the catabolism and clearance of TCII in this patients is impaired with increased TCII excretion in the urine in parallel to the hemoglobinuria. Serum TCII level is, therefore, increased and persistently high in a patient with malaria and typhus fever infections with hemoglobinuria.

Serum transcobalamin II levels in patients with acute and chronic renal failure.

Serum TCII levels were determined in 57 patients with acute and chronic renal failure. They were divided into 3 groups, group I was malarial patients with acute renal failure, group II and III were patients with acute renal failure and chronic renal failure from other underlying causes, respectively. All patients in group I had serum TCII over 2000 pg/ml while these values were within the normal limits in the other 2 groups. These findings indicated that elevated serum TCII occurred only in malarial patients with acute renal failure. The clearance and urinary excretion of TCII in malarial patients were found to be lower and increased to the normal levels after recovery from azotemia, indicating that the failure of excretion of TCII by the kidneys may be responsible for elevated serum TCII levels. The pathophysiological changes in the kidneys in malarial patients may reduce the amount of filtered TCII-B12 through the glomeruli and decrease TCII-B12 uptake by the renal tubules resulting in the decreased TCII degradation by tubular cells. Therefore, the intravascular TCII survival is prolonged with elevated serum TCII levels in these patients.

Abnormally elevated serum transcobalamin II levels in patients with cerebral malaria.

Transcobalamin II (TCII) levels have been reported to be elevated in patients with many clinical conditions including proliferative reticuloendothelial system. As reactive macrophage hyperplasia frequently occurs in patients with malaria, the objective of the present study was to determine TCII in patients with Plasmodium falciparum with cerebral symptoms. The studies were performed on 14 cerebral malaria patients as well as 60 normal subjects. The mean values of serum vitamin B12 and TCII levels were significantly higher in the patient group and 6 and 7 patients had serum vitamin B12 and TCII levels higher than the normal values. There was direct relationship between serum TCII levels and BUN or creatinine levels. These findings indicated that raised serum TCII level occurred only in patients with renal insufficiency. A decreased glomerular fiLtration rate reduced the amount of vitamin B12 and TCII-B12 that filtered through the glomeruli resulting in the reduced proximal tubular cells uptake and its degradation of TCII. This reduced lysosomal enzyme activity, therefore, prolongs the intravascular TCII survival and increased secretion of TCII into the circulation. Therefore, serum TCII levels were elevated in these cerebral malaria patients.

The source and content of vitamin B12 in the tempehs.

Vitamin B12 contents were determined on 10 commercial tempeh samples purchased from various markets in Jakarta, Indonesia. A relatively high vitamin B12 content was found, i.e., 19 ng/g (ranges from 1.8 to 41.4 ng/g). As soybeans contain no vitamin B12, the amount of vitamin in the tempeh must therefore be derived from the other sources during the fermentation process. The tempeh prepared in the laboratory by inoculation of the commercial starter into the sterile soybean contained a much higher amount of vitamin B12, 127 ng/g (ranges from 122 to 136 ng/g). Pure mold and a single species of bacteria were isolated from the starter and commercial tempehs. Pure mold did not produce vitamin B12 in the sterile broth, soybean and medium used for vitamin B12 production. Only the isolated bacteria, identified as K. pneumoniae, could produce vitamin B12 in those substrates. The presence of mold did not significantly enhance or inhibit the vitamin B12 production by K. pneumoniae. It was, therefore, concluded that K. pneumoniae, the bacteria contaminated during the process of tempeh production, was responsible for the vitamin B12 production.