Serum levels of thyroxine-binding prealbumin, C-reactive protein and interleukin-6 in protein-energy undernourished children and normal controls without or with associated clinical infections.

We measured the levels of thyroxine-binding prealbumin (TBPA), C-reactive protein (CRP), and interleukin-6 (IL-6) in sera from protein-energy undernourished and control children either without or with associated clinical infections. Levels of TBPA were significantly lower in undernourished than in control children without clinical infections. Mean serum TBPA concentration was also significantly lower in both clinically infected undernourished and control children than in those of the same nutritional status but without overt infections.

Production of interleukin-6 in cultures of peripheral blood mononuclear cells from children with primary protein-calorie malnutrition and from eutrophic controls.

The spontaneous as well as mitogen-induced in vitro production of interleukin-6 (IL-6) was studied in cultures of peripheral blood mononuclear cells (PBMC) from 14 children with marginal protein-energy malnutrition, 43 children with definite protein-energy malnutrition and 38 eutrophic controls of similar age, sex, race and socioeconomical condition. PBMC were cultured without added mitogen or stimulated with either lipopolysaccharide (LPS) or phytohemagglutinin (PHA). After 48 h incubation, cell-free culture supernatants were collected and stored at -70 degrees C.

[Serum levels of prealbumin in undernourished children and controls with or without associated clinical infection].

Due to its short half life and high tryptophan content, prealbumin has been considered a sensitive indicator of protein and/or energy deficiency. In addition, prealbumin diminishes during the acute phase response elicited by either infection or tissue injury. Serum levels of prealbumin were determined in undernourished children with or without associated clinical infection and in their infected or non-infected controls matched for age, sex, race and socioeconomical conditions.

Antibodies to dietary antigen in serum from patients with sickle cell anemia.

The levels of antibodies of the IgG, IgA and IgM isotypes reacting against ovoalbumin (OVA), gliadin (GL) and cow's milk proteins (CMP), were determined by ELISA in sera from a group of adult patients with sickle cell anemia (SCA) bearing homozygous Ss hemoglobinopathy and from matched health donors. Only patients with steady-state disease were included in the study. Increased amounts of IgG and IgA reacting with OVA, GL and CMP were observed in the group of patients as compared with the controls.

Levels of tumor necrosis factor alpha/cachectin (TNF alpha) in sera from patients with sickle cell disease.

Serum levels of tumor necrosis factor alpha/cachectin (TNF alpha) were studied in a group of adult patients with sickle cell disease (SCD), which include 31 patients with homozygous SS hemoglobinopathy and 10 patients bearing double heterozygous SC hemoglobinopathy and in their matched normal controls. All patients tested did not show any form of crisis for at least 4 weeks prior to the extraction of the sample. The amount of TNF alpha in serum was quantitated by means of an immunoenzymatic assay with a lower limit of detection of 25 pg/ml.

[Changes in the serum lipid fractions of malnourished children with and without clinical infection. Paradoxical hypertriglyceridemia in malnutrition].

We have studied the levels of total triglycerides, total cholesterol and high, low and very low density lipoproteins, in serum from undernourished children and from eutrophic controls matched by age, race and socioeconomical condition with the undernourished group. Malnourished children were classified according to the severity of the nutritional deficiency and according to the presence or absence of associated overt infections. Serum lipids fractions were evaluated by colorimetric procedures and by electrophoretic isolation and elution of the desired lipoprotein followed by colorimetric evaluation of the cholesterol content.

[Relation of fat consumption to colorectal cancer mortality in a Venezuelan population].

Epidemiologic and experimental studies have pointed to an association between fat intake and colorectal carcinogenesis. In the present work we have studied the correlation between fat intake and mortality caused by colorectal cancer in the venezuelan population. For this purpose, we have calculated the correlation coefficients between the ingestion of total fat, visible fat (vegetable oil, margarine, butter, mayonnaise) as well as non-visible fat (that contained in other foods) and the mortality rate by colorectal cancer with data from nine venezuelan states and geographical regions.

Mitogenic effect of zinc on lymphocytes from strains of mice that are either high or low-responder to T-cell mitogens.

We have studied the in vitro mitogenic effect of ZnCl2 in cultures of lymphocytes from Balb/c or C57BL/6 mice which are high-responder or low-responder to T-cell mitogens respectively. Zn induced proliferation of spleen cells from Balb/c mice cultured without 2-ME. Higher levels of proliferation were observed in cultures with 2-ME.

Influence of the oral administration of excess copper on the immune response.

We have studied the influence of the oral administration of excess copper (Cu) on the immune response. With this aim, mice maintained on standard laboratory diet received 50, 100, 200, or 300 ppm of Cu as copper sulfate in the drinking water during 3 to 10 weeks. Inhibition of the proliferative response to concanavalin A was observed in mice exposed to 100 ppm of Cu for 8 weeks and to 200 ppm of Cu for either 3 or 8 weeks.

Effect of zinc on the proliferative response of human lymphocytes: mechanism of its mitogenic action.

To study the effect of Zn on the proliferative response of normal human lymphocytes, ZnCl2 at a final concentration of 10(-4) M was added to cultures of peripheral blood mononuclear cells (PBMC) stimulated with concanavalin A (Con A) and to autologous mixed lymphocyte cultures of responder T lymphocytes and irradiated autologous non-T cells. Addition of Zn increased by about 50% the synthesis of DNA in cultures stimulated with either 10 or 20 micrograms/ml of Con A and markedly enhanced the autologous mixed lymphocyte reaction, which increased about 5-fold in the presence of Zn. In a narrow dose range, Zn induced per se the incorporation of [3H]thymidine by PBMC, with maximal effects in cultures stimulated with 10(-4) M ZnCl2.

In vitro antibody synthesis by peripheral blood mononuclear cells from patients with sickle cell disease.

To study the capacity of peripheral blood mononuclear cells (PBMC) from patients with sickle cell disease to synthesize antibodies in vitro, the levels of IgM, IgG, and IgA were quantitated in supernatants of cultured PBMC from a group of asymptomatic adults with sickle cell disease and from normal controls. The rates of spontaneous synthesis of IgM were similar in nonstimulated cultures of PBMC from patients and controls, whereas the amounts of IgG and IgA produced spontaneously by nonstimulated lymphocytes from the patients were significantly greater than those from controls. Similar levels of IgM, IgG, and IgA were detected in the supernatants of cultures stimulated with pokeweed mitogen from patients and controls.

Zinc administration restores the impaired immune response observed in mice receiving excess copper by oral route.

To study if treatment with zinc (Zn) was able to restore to normal levels the depressed immune response determined by oral administration of excess copper (Cu), groups of mice receiving 100 ppm or 200 ppm of Cu in the drinking water for 8 weeks, were injected ip once a week with Zn (1.14 mg/kg of body weight), throughout the experimental period. Administration of Zn restored to normal levels the proliferative response to mitogens and the antibody response to sheep red blood cells in the group of mice receiving 100 ppm of Cu in the drinking water.

Production of tumor necrosis factor/cachectin by peripheral blood mononuclear cells in patients with systemic lupus erythematosus.

Levels of tumor necrosis factor/cachectin (TNF alpha) assessed by ELISA were similar in the supernatant of cultures from peripheral blood mononuclear cells (PBMC) from either active or inactive systemic lupus erythematosus (SLE) patients and controls stimulated with mitogen alone. When PBMC were stimulated with mitogen plus phorbol 12-myristate-13-acetate (PMA), the amount of TNF alpha was significantly decreased in culture supernatants from active patients or from the entire group of SLE patients studied. However, spontaneous synthesis of TNF alpha in nonstimulated cultures was increased in the SLE patients.

Calorie restriction modifies the delayed-type hypersensitivity response to the hapten trinitrobenzenesulfonic acid and to hapten-modified syngeneic spleen cells.

We have studied the influence of different degrees of calorie restriction on the induction and the regulation of the delayed type hypersensitivity (DTH) response to trinitrobenzenesulfonic acid (TNBS) and TNBS-modified spleen cells (TNBS-SC), injected by the sc or the iv route. Immediately after weaning, BALB/c mice were placed on restricted diets for either 2 or 4 weeks and then the DTH response was induced. The results showed that a 37.

Mitogen induced lymphoproliferative responses and lymphocyte sub-populations in patients with sickle cell disease.

Mitogen induced lymphoproliferative responses and lymphocyte sub-populations were studied in a group of sickle cell disease (SCD) patients with homozygous SS hemoglobinopathy. Even though the response to a sub-optimal dose of Con A (0.5 microgram/ml of culture) was significantly decreased in patients with SCD, the proliferative responses to optimal doses of Con A, to PHA and to PWM were preserved in the patients.

Differences in the effect of indomethacin and preincubation on the lymphoproliferative response to concanavalin A of spleen cells from low responder C57BL/6 and high responder BALB/c mice.

In vivo treatment with 100 micrograms of indomethacin each 48 h for 2 weeks enhanced the proliferative response to concanavalin A (Con A) of spleen cells from mice of the C57BL/6 (B6) strain, low responder to T cell mitogens, but did not modify the response of spleen cells from mice of the high responder strain BALB/c (C). The enhancing effect of in vivo indomethacin treatment was more marked in cultures of B6 splenocytes stimulated with high, moderately supraoptimal doses of Con A than in cultures stimulated with optimal mitogen doses. Addition of indomethacin to cultures of spleen cells from untreated donors induced greater increase of the lymphoproliferative response of cells from low responder B6 than from high responder C mice.

Influence of protein restriction on lymphoid cell populations characterized by the binding of peanut agglutinin.

Cells binding peanut agglutinin (PNA) were studied in the thymus, spleen, and mesenteric lymph nodes from mice placed in the post weaning period on protein-restricted diets containing 8% (R8%) and 4% (R4%) casein. The proportion of PNA+ thymocytes and the absolute number of total and PNA+ cells in the thymus were significantly diminished in R8% and R4% mice. Larger proportion of PNA+ thymocytes showed weaker fluorescence in R8% and R4% than in normally fed (N) animals.

Modulatory effect of zinc on the proliferative response of murine spleen cells to polyclonal T cell mitogens.

To study the effect of zinc on the proliferative response to polyclonal T cell mitogens, spleen cells from C57BL/6 mice were cultured with or without ZnCl2 and stimulated with graded doses of concanavalin A or phytohemagglutinin. Addition of 10(-4) M ZnCl2 inhibited proliferation whereas 10(-5) to 10(-6) M ZnCl2 did not modify the response to suboptimal doses of mitogen but increased DNA synthesis in cultures stimulated with high doses of mitogen (10 or 20 micrograms/ml of concanavalin A and 10 or 25 microliters/ml of phytohemagglutinin) which are supraoptimal for C57BL/6 mice, and inhibited proliferation in cultures of spleen cells from animals of this strain, low responder to T cell mitogens. In contrast, supplementation with ZnCl2 did not enhance the response to mitogen of spleen cells from high responder BALB/c mice.

Affinity and distribution of subpopulations of antibody-producing cells in protein-restricted C57BL/6 mice.

To study the effect of protein restriction on the affinity of antibodies produced by plaque-forming cells (PFC), C57BL/6 mice were fed diets containing 4% (R4%), 8% (R8%), or 27% (N) casein for 2 (short-term) or 12 (long-term) weeks and immunized with dinitrophenyl (DNP) bovine gamma-globulin in complete Freund's adjuvant. Affinity was assessed by inhibition of plaque formation in the presence of free hapten. Anti-DNP PFC per 10(7) spleen cells were not diminished in short- and long-term R8% mice, and were increased in the former group at certain times after immunization.

The effect of protein restriction on the development of protective immunity to Leishmania mexicana.

Protein deprived C57BL/6 mice infected with 10(3) amastigotes of Leishmania mexicana showed early arrest of lesion progression during the first 5 weeks of infection with subsequent development of progressive non-healing lesions. In contrast, well nourished mice similarly infected developed gradual healing lesions. The early resistance of malnourished mice to 10(3) amastigotes was overcome by a larger dose.

Altered immune response during cadmium administration in mice.

C57BL/6 mice were administered 50 or 200 ppm of Cd as CdCl2 in the drinking water for either 3 to 4 (short term) or 9 to 11 (long term) weeks. In other experimental designs, mice were exposed orally to 300 ppm of Cd or injected with 2.5 mg/kg of Cd ip.

Influence of dietary protein restriction on the delayed-type hypersensitivity response to sheep red blood cells in mice.

Delayed-type hypersensitivity responses to sheep erythrocytes were studied in inbred C57BL/6 and outbred NMRI mice fed either protein-deficient diets containing 8% and 4% casein or a normal diet with 27% casein. Following sensitization with optimal doses of antigen, the magnitude of the response was similar in mice fed the 8% protein and the normal diet. Large numbers of sheep red blood cells which suppressed the delayed hypersensitivity response in normal mice, failed to inhibit this response in animals fed the 8% casein diet.

Modulation by zinc of the in vitro antibody response to T-dependent and T-independent antigens.

The influence of zinc on the in vitro antibody response to antigen or mitogen stimulation was studied by adding various concentrations of ZnCl2 to cultures of spleen cells stimulated with sheep erythrocytes, trinitrophenyl-lipopolysaccharide or with the polyclonal B cell activator E. coli lipopolysaccharide (LPS). Addition of ZnCl2 in concentrations ranging from 10(-8) or 10(-7) to 10(-5) M increased the specific antibody response to antigens or the polyclonal antibody synthesis induced by stimulation with LPS, when the response of the assayed population in the control cultures without ZnCl2 was low, as observed in cultures without 2-mercaptoethanol (2-ME).

Polyclonal B-cell response to stimulation with Escherichia coli lipopolysaccharide in dietary protein restriction.

The polyclonal B-cell response to Escherichia coli lipopolysaccharide was studied in C57BL/6 mice maintained after weaning on either a moderate protein-restricted diet with 8% casein or a normal diet. After in vitro or in vivo stimulation with the endotoxin, autoreactive and anti-hapten antibody-producing cells were quantitated by direct plaque assay, using bromelain-treated mouse erythrocytes and trinitrophenylated sheep erythrocytes as targets. Larger numbers of plaque-forming cells were generated in cultures of spleen cells from dietary-restricted than from normal mice stimulated with various doses of lipopolysaccharide.

Enhancement of the in vitro antibody response in dietary protein restriction. Failure in the regulation of antibody synthesis.

We have studied the antibody response in vitro of spleen cells from C57BL/6 mice kept on a protein deficient (D) or a normal diet (N). Short or long term protein restriction initiated after weaning led to increased plaque forming cell (PFC) responses to sheep red blood cells (SRBC), TNP-ficoll and TNP lipopolysaccharide. The influence of dietary restriction on the suppression of the antibody response to SRBC was studied in mixed cultures of antigen sensitized and fresh, non-immune cells from either D or N donors.