Fractionation of Crotalus durissus cumanensis venom by gel filtration

Serum lipid levels were determined in 30 children with kwashiorkor and in 30 healthy children of comparable age. The serum concentrations of unesterified and esterified cholesterol, albumin and the cholesterol esterifying activity (CEA) were also measured in children with kwashiorkor before treatment and after recovery. All serum lipid fractions were significantly lower in kwashiorkor than in the normal children. After treatment and recovery, serum lipid levels were comparable to those observed in normal children. There was also a significant increase in serum cholesterol esterifying activity (CEA) following recovery from kwashiorkor.     

Severe hypophosphatemia in children with kwashiorkor is associated with increased mortality

Severe hypophosphatemia, serum phosphate concentration <0.32 mmol/L (<1.0 mg/dL), occurred in 8 of 68 (12%) of children with kwashiorkor within 48 hours of admission; 5 of 8 (63%) of these children died, compared with 13 of 60 (22%) children without severe hypophosphatemia (P <.02). Dermatosis and dehydration were significantly correlated with severe hypophosphatemia, but these clinical signs could not reliably predict fatal cases. Severe hypophosphatemia seems to be common and life-threatening in children with kwashiorkor in Malawi.     

Sarcomas in syrian hamster, induced by an oncorna virus and cellfree transmissible (author''s transl)]

A previous study had shown that in children with third degree protein-energy malnutrition, ultrafilterable or diffusible serum calcium concentrations remain normal, while the protein-bound fraction is low in those with hypoalbuminemia, accounting for over-all hypocalcemia. In order to retest those findings, a new series consisting of 20 small marasmic infants and 16 children with kwashiorkor was studied, using a membrane ultrafiltration procedure. Fifteen eutrophic children served as controls. At time of their admission into hospital, both groups of patients showed hypocalcemia, more so the cases of kwashiorkor. Diffusible calcium was normal, while the protein-bound moiety was significantly decreased in children with kwashiorkor. Upon recovery, protein-bound as well as total calcium concentrations returned to normal values.     

Structure and biologic functions of human IgD. X. Enhancement of PHA responsiveness by anti-delta-activated lymphocytes

Human peripheral lymphocytes with the capacity to be stimulated by anti-delta exhibited in PHA responsiveness when cultured with anti-delta 1 or 12 hr before PHA exposure over cells exposed to PHA alone. When these lymphocytes were preincubated with PHA 1 or 12 hr before anti-delta activation, no augmentation of the PHA response was seen. In addition, lymphocytes from donors with a high PHA response (low anti-delta activation) failed to show an enhancing effect on PHA responsiveness when pretreated with anti-delta. Moreover, anti-mu showed no synergistic effect on PHA responsiveness. This study is the first to indicate that anti-delta-activated cells enhance PHA responsiveness.     

Lipids and lipoproteins of malnourished children during early renutrition: apolipoprotein A-IV as a potential index of recovery

Twenty-six children with marasmus and 27 with kwashiorkor were compared with 23 control children of matching ages. Kwashiorkor was characterized by increased phospholipids (NS), low (P < 0.01) apolipoprotein (apo) B-rich LDL, and near normal apo A-I and HDL-C. In children with marasmus apo B (P < 0.02) LDL-C (NS), apo A-I (P < 0.01), and HDL-C (P < 0.001) decreased. Fifteen children in each group were followed for 2 wk. Control values were progressively reached after 2 wk. In the younger children final apo B was higher than in control subjects (P < 0.03) but apo A-I was identical. Apo A-IV, assayed because it correlates with the functional state of intestine, was near normal in children with kwashiorkor and decreased with treatment. In children with marasmus apo A-IV decreased by 50%, increased with treatment in older children, but further diminished in younger children. After 2 wk apo A-IV was significantly lower in all patients than in control subjects. Apo A-IV, by remaining depressed after other variables normalized, seems a good index of nutritional status.     

Sequential expression of lymphokine genes during phytohemagglutinin-stimulated mitogenesis of normal human peripheral mononuclear cells

Expression of lymphokine genes including interleukin 2 (IL-2), interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-g), tumor necrosis factor (TNF) and lymphotoxin (LT) were sequentially monitored in peripheral blood mononuclear cells by Northern blot analysis after stimulation with phytohemagglutinin (PHA). The pattern of the expression of lymphokine genes following PHA stimulation as categorized into two types. Type 1 was characterized by rapid appearance of mRNA and by early maximum accumulation. Type 2 was characterized by the prolonged expression and late peak time. Lymphokines including IL-2, IL-3 and GM-CSF belong to type 1 and IFN-g, TNF and LT belong to type 2. Since lymphokines in type 1 are known to act on hematopoiesis in a stimulatory manner, whereas type 2 show an inhibitory action, this sequential expression of lymphokines following mitogen stimulation may reflect some biological feedback mechanism.     

Palatine tonsils and immunity. VIII. Soluble factors produced by lymphocytes of the palatine tonsils and other lymphoid formations in rabbits

A comparison was made of the activity of solbule factors produced by thelymphocytes of the palatine tonsils, the appendix, the spleen and thelymph nodes of rabbits in stimulation with a specific antigen (complete antigen of streptococcus, group A) and PHA. The blastogenic factor produced by the lymphoid cells of the spleen and the lymph nodes was highly active. Lymphocytes of the palatine tonsils and of the appendix produced a factor withlow activity after PHA stimulation. A factor intensifying the transformation in the presence of a complete streptococcus antigen was produced by lymphocytes of the spleen and the lymph nodes of the immunized animals. The lymphocytes of the palatine tonsils and the appendix failed to produce this factor.     

Release of endogenous pyrogen-activating factor from concanavalin A-stimulated human lymphocytes

Evidence is presented that the mitogen concanavalin A stimulates human lymphocytes to produce a nonpyrogenic lymphokine (LK) that is capable of activating human monocytes but not granulocytes to produce endogenous pyrogen (EP) in vitro. The potency of this preparation should facilitate further studies to purify and characterize this agent and determine its relation to other know LK. It seems likely that this factor, which we have called EP-activating factor (EPAF), plays a significant role in the development of fever in states of delayed hypersensitivity in man.     

Detection of carriers of hemophilia by hemorrhagometry

Children with respiratory virus infections and healthy contacts were given leukocytic interferon (LIF) as treatment and prophylaxis. The results emphasize the effectiveness of the treatment when LIF was given on the 1st or 2nd day after onset of illness. In these cases the course was mild, of short duration and without complications. In children who did not receive LIF, the clinical course was more severe, the disease lasted longer, and complications were not uncommon. Prophylactic instillation of LIF succeeded in preventing the disease in 85.2% of the contacts; those who contracted the infection had a mild disease with insignificant complications. No allergic or intoxication phenomena were observed in children receiving LIF.     

Of sick turkeys, kwashiorkor, malaria, perinatal mortality, heroin addicts and food poisoning: research on the influence of aflatoxins on child health in the tropics

Similarities between the geographical and climatic prevalences of kwashiorkor and of exposure to dietary aflatoxins, and between the biochemical, metabolic and immunological derangements in kwashiorkor and those in animals exposed to aflatoxins, prompted investigation of the associations between kwashiorkor and aflatoxins. Studies in Africa in the 1980s indicated a role for these toxins in the pathogenesis of the disease. Paediatric cases of kwashiorkor are less prone to severe Plasmodium falciparum malaria than normal children. In mice infected with P. berghei, aflatoxin exposure inhibits parasite growth and ameliorates morbidity. Aflatoxins occur in < or = 40% of samples of breast milk from tropical Africa, usually as low concentrations of the relatively non-toxic derivatives of aflatoxin B1 (AFB1) but sometimes as high concentrations of the very toxic AFB1. This could explain kwashiorkor in breast-fed babies. Aflatoxin exposure occurs in > or = 30% of pregnancies in tropical Africa and the toxins are often in cord blood, sometimes at extremely high concentrations. Aflatoxins are now incriminated in neonatal jaundice and there is circumstantial evidence that they cause perinatal death and reduced birthweight. Aflatoxin-induced immunosuppresion may explain the aggressive behaviour of HIV infection in Africa. There are similarities between observations on HIV cases in Africa and those on heroin addicts in Europe, where 'street' heroin is frequently contaminated with aflatoxin. Aflatoxins were found in 20% of random urine samples from heroin addicts in the U.K. and the Netherlands. Aflatoxins have also been incriminated in episodes of food poisoning which have been associated with serious morbidity and mortality, particularly among young children.     

A comparison of phorbol myristate acetate with phytohemgglutinin as a stimulator of in vitro colony growth of peripheral human leucocytes

Peripheral blood mononuclear cells from normal individuals were cultured in soft agar (0.3%) with either phytohaemagglutinin (PHA) or the tumor promoter phorbol myristate acetate (PMA). PMA was found to induce colony growth under these conditions as well as that achieved by PHA. The colonies from PHA stimulation were entirely lymphoid but with PMA the type of cell was more varied with some cells that appeared to be of the granulocytic-macrophage line. PMA thus appears to have the ability to promote growth in cells other than lymphocytes in the peripheral blood under these conditions.     

Differences in the stress response of Wistar-Kyoto (WKY) rats from different vendors

This study tested the hypothesis that during treatment of kwashiorkor (including marasmic kwashiorkor) with infection there is a lower rate of amino acid oxidation when the dietary intake of amino acids resembles the amino acid composition of acute phase proteins (APPs). Twenty-two children in Blantyre, Malawi, with kwashiorkor and acute infection were fed an isoenergetic, isonitrogenous diet with either egg white or milk as a protein source. The whole-body amino acid oxidation rate was measured after 24 h by determining the plasma urea rate of appearance, and whole-body protein breakdown and synthesis rates were determined from the plasma leucine rate of appearance. Plasma concentrations of C-reactive protein, alpha1-antitrypsin, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) were determined on admission and at 24 and 48 h. The 11 children who received milk had a lower rate of amino acid oxidation than the children who received egg white (x +/- SD: 137 +/- 65 compared with 195 +/- 66 micromol urea x kg body wt(-1) x h(-1), P < 0.05). No significant differences were found between the two groups in the rate of whole-body protein breakdown or protein synthesis. The TNF-alpha concentration correlated inversely with whole-body protein breakdown and synthesis rates, and the IL-6 concentration correlated directly with C-reactive protein. We conclude that by making the amino acid composition of the diet resemble that of APPs in the treatment of acute kwashiorkor, the rate of amino acid oxidation can be decreased.     

Stress and the immune response in rats

The in vitro response of sensitized splenic lymphocytes to antigen (thyroglobulin) was increased by crowding and decreased by isolation in female rats. Both isolated and crowded male rats responded by a decrease in the in vitro reactivity of lymphocytes to antigen. The response of the lymphocytes to PHA was not altered in any consistent manner. Similar animals, both control and those immunized with thyroglobulin, were tested for an effect of in vivo injections of epinephrine on the in vitro reactivity of lymphocytes; epinephrine was given intraperitoneally 30 min before the rats were killed for removal of spleens. Incorporation of 3H-thymidine by lymphocytes was greater in control cultures (neither PHA nor antigen present) but there was a decreased response to either PHA or antigen when epinephrine had been injected.     

Iron-containing proteins augment responses of human lymphocytes to phytohemagglutinin and pokeweek mitogen in serum-free medium

The effects of various iron-containing compounds on the responses of human peripheral lymphocytes to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were studied in serum-free medium supplemented with bovine serum albumin. Hemoglobin, transferrin and ferritin enhanced the incorporation of 3H-thymidine into DNA after PHA-stimulation of lymphocytes, while hemin, iron metal powder, ferrous sulfate, chromium powder, and zinc sulfate have little effect. The response to PWM, measured by plaque formation, was enhanced only by transferrin. Desferrioxamine, a chelating agent specific for ferric iron, completely removed these augmentative effects. The results indicate that iron-containing proteins influenced the responses of lymphocytes to stimulation by PHA and PWM in serum-free medium.     

Identification of mycobacteria by mycolic acid pattern

In this study the authors assessed plasma leukaemia inhibitory factor (LIF), interleukin 6 (IL-6) and soluble IL-6 receptor (sIL-6R) concentrations in 28 patients undergoing coronary artery bypass graft (CABG) with extracorporeal circulation (ECC). Plasma IL-6 levels increased during ECC, reaching a 33-fold increase 6 h after surgery as compared to pre-operative values. In contrast, plasma sIL-6R and LIF concentrations did not vary significantly during cardiac surgery. Thus, LIF is not implicated in the haematological changes and in the inflammatory syndrome observed after CABG. Despite the fact that LIF and IL-6 exhibit several common biological activities, the production of these two cytokines is differently regulated during cardiac surgery with ECC. Plasma IL-6 levels increased during cardiac surgery while sIL-6R levels did not changed. These data contrast with the decreased sIL-6R concentrations with concomitantly high IL-6 levels in patients with sepsis syndrome suggesting that inflammatory reactions in sepsis and after cardiopulmonary bypass are triggered by different mechanisms.     

The role of T lymphocytes in patients with food-sensitive atopic dermatitis

The role of T lymphocytes was assessed in patients with food-sensitive atopic dermatitis (AD). T lymphocytes plus monocytes responded well to ovalbumin or bovine serum albumin (BSA) in children with AD who were sensitive to hen's egg or cow's milk compared with healthy children and children with immediate allergic symptoms who are sensitive to hen's egg or cow's milk. The responding cells were shown to be predominantly CD4+ T lymphocytes. Interleukin-2 activity and interferon-gamma concentrations in culture supernatants of ovalbumin-stimulated peripheral blood mononuclear cells (PBMCs) from patients with AD who were sensitive to hen's egg were significantly higher than those of healthy children and patients sensitive to hen's egg with immediate symptoms. Expression of Fc epsilon R II on B lymphocytes in cultures of ovalbumin-stimulated PBMCs from patients with AD was significantly higher than that of healthy children, but it tended to be lower than that of patients with immediate symptoms. These results suggest that, in patients with AD who are food sensitive, CD4+ T lymphocytes stimulated by food antigens secrete lymphokines such as interleukin-2 and interferon-gamma that are secreted from TH1 clones in mice, and express Fc epsilon R II on B lymphocyte that is induced by interleukin-4 secreted from TH2 clones in mice. Taken together, cell-mediated immunity may also occur in addition to IgE-mediated hypersensitivity in patients with food-sensitive AD.     

The chemotactic attraction of human fibroblasts to a lymphocyte-derived factor

A quantitative assay that measures fibroblast chemotaxis in vitro is described. Application of this technique has revealed that peripheral blood lymphocytes stimulated by antigen or mitogen in vitro produce a factor that is chemotactic for human dermal fibroblasts. This lymphocyte-derived chemotactic factor for fibroblasts (LDCF-F) is different from the lymphokine that is chemotactic for monocytes or macrophages. Macrophages are required for the generation of LDCF-F by T lymphocytes stimulated by phytohemagglutinin. The fibroblast chemotactic factor is heat stable (56 degrees C for 30 min), trypsin sensitive, and neuraminidase resistant. LDCF-F could function to attact connective tissue fibroblasts to sites at which cell-mediated immune reactions are occurring in vivo.     

Subtype and sequence analysis of the C2-V3 region of gp120 genes among HIV-1 strains in Hubei province

Eight (14 per cent) out of 57 consecutive cerebral malaria patients (all < 5 years old) were malnourished, including one with marasmus and another recovering from kwashiorkor. This was significantly lower than among other paediatric patients in the same children's emergency ward (112/319, i.e. 35 per cent, P < 0.01). Poor outcomes (death or recovery with neurological deficits) were commoner in the malnourished group (4/8) than the well nourished group (7/49) (P = 0.037, Fisher's exact test). Malnourished children should receive malaria chemoprophylaxis during nutritional rehabilitation.     

A double-blind comparison of the efficacy and safely of paroxetine and imipramine in the treatment of depression with dementia

Marrow stromal cells of patients treated by autologous bone marrow transplantation (ABMT) for malignancies have been assessed for their ability to secrete granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), transforming growth factor beta1 (TGFbeta1) and macrophage inflammatory protein-1alpha. (MIP-1alpha). Long-term marrow cultures were established from 10 patients prior to and 3 months after ABMT, from 7 patients 1 yr after ABMT and from 11 controls. Cytokines in culture supernatants of stromal layers (SL) were evaluated by enzyme-linked immunosorbent assay (ELISA). Significant differences between patient groups and controls were apparent in baseline production of GM-CSF, SCF, MIP-1alpha and TGFbeta1. After IL-1beta addition in cultures, G-CSF production was reduced in pretransplant and post-transplant patients compared to controls. The production of TGFbeta1, LIF, IL-6 and more particularly SCF were reduced in post-transplant patients, while elevated levels of GM-CSF and MIP-1alpha were observed in these patients only when the values were corrected for the number of cells growing in the SL. These results indicate a prolonged stromal defect in growth factor production following ABMT for the early-stage acting cytokines IL-6, LIF and SCF as well as for G-CSF, but not for GM-CSF, while the production of the 2 inhibitors shows different pathways.     

Impaired blastogenic response of lymphocytes from synovial fluid and peripheral blood of patients with rheumatoid arthritis

Synovial fluid lymphocytes from patients with rheumatoid arthritis demonstrated a markedly diminished blastogenic response to both phytohemagglutinin and pokeweed mitogens, when compared to normal peripheral blood lymphocytes. The blastogenic response to rheumatoid peripheral blood lymphocytes to both mitogens was also depressed, when compared to the response of normal lymphocytes, but the difference was less marked and was within limits which could be accounted for by recent salicylate therapy. Lymphocytes of both peripheral blood and synovial fluid of rheumatoid patients showed a delayed response to PHA (five days to achieve maximum thymidine incorporation vs four days for normals).