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Biomedical subjects

L Sirota

Publications and source records attributed to L Sirota.

At least 73 records · Page 4Linked to original sources

Effect of dexamethasone on IL-2 and IL-3 production by mononuclear cells in neonates and adults.

The effect of dexamethasone on interleukin 2 (IL-2) and interleukin 3 (IL-3) production by mononuclear cells in preterm and term infants and adults was evaluated. The capacity of mononuclear cells to produce these cytokines, in preterm infants with bronchopulmonary dysplasia (BPD) and treated with dexamethasone, was compared with that before treatment. Twenty six preterm and 36 term neonates and 24 healthy adults were included in the study. Mononuclear cells isolated from neonatal cord blood (CBMC) and adult peripheral blood (PBMC) were stimulated with phytohaemagglutinin (PHA) in the absence or presence of dexamethasone at concentrations between 10(-8)M and 10(-5)M. IL-2 and IL-3 activities in the supernatant fluids were tested using bioassays. The in vivo effect of the drug on the production of these cytokines by PBMC in 10 preterms was determined before and 24 hours after dexamethasone administration (0.5 mg/kg/day). The production of both cytokines was inhibited in a dose dependent manner. A difference in the sensitivity of mononuclear cells to the inhibitory effect of the drug was found between neonatal cord blood cells and adult PBMC, the former being more sensitive. PBMC from preterm infants treated with dexamethasone for BPD produced significantly less IL-2 and IL-3 as early as 24 hours after the initiation of the treatment (43% and 31%; P < 0.05, respectively). It is concluded that mononuclear cells from preterm and term neonates are more sensitive to the inhibitory effect of dexamethasone on IL-2 and IL-3 production.

Adult↗

Human colostrum stimulates cytokine production.

The effect of human colostrum on the production of IL-1, IL-3 and IL-6 by peripheral blood mononuclear cells (PBMCs) has been investigated. The aqueous phase of human colostrum significantly stimulated the production of these three cytokines. These findings show the importance of breast feeding not only as a well-balanced nutrient supply but also as a source for growth-promoting factors. It is suggested that the enhanced secretion of IL-1, IL-3 and IL-6 induced by human colostrum may compensate for the lower capacity of neonatal PBMCs to produce these cytokines. It is also possible that, by stimulating the secretion of these cytokines, breast feeding may provide an additional mechanism for the regulation of the neonatal immune system and hematopoiesis.

Colostrum↗

Are bilirubin and plasma lipid profiles of premature infants dependent on the lipid emulsion infused?

The effect of a lipid emulsion containing long-chain triglycerides (LCT) and supplemented with L-carnitine on plasma lipids and bilirubin in premature neonates on total parenteral nutrition was compared to that of lipid emulsions containing either LCT or a mixture of LCT and medium-chain triglycerides (MCT). In a double-blind randomized study 49 premature neonates received one of the three fat emulsions, given intravenously, over 16-20 h daily for 6 days. Plasma carnitine levels increased significantly in the supplemented group only; the addition of carnitine did not seem to affect any of the parameters studied. Mean plasma triglycerides rose by 193 and 199% in the carnitine-supplemented and the LCT groups, respectively, and by 314% in the MCT/LCT group. On the sixth day of the study free fatty acids were significantly higher in the MCT/LCT group than in the other two groups. Plasma phospholipids and free cholesterol increased (p < 0.05) progressively in all groups and were correlated (r = 0.74, p < 0.001). At the end of the 6-day study all groups showed a similar decline in free and total bilirubin levels despite the significant increase in plasma lipids and free fatty acids resulting from the stepwise increase in lipid load. No correlation was found between free fatty acids and free bilirubin. Since hyperbilirubinemia and hypertriglyceridemia appear to be clinically independent factors, the infusion of lipids should not be withheld from jaundiced infants on total parenteral nutrition.

Bilirubin↗

Effect of human colostrum on interleukin-2 production and natural killer cell activity.

The effect of human colostrum on the production of interleukin-2 (IL-2) and on natural killer (NK) cell activity by peripheral blood mononuclear cells (PBMC) was investigated in 50 healthy women. At concentrations as low as 0.5%, human colostrum stimulated IL-2 production; at a higher concentration (10%), IL-2 secretion was inhibited. A time and dose dependent inhibitory effect of colostrum on NK cytotoxicity was also observed. This inhibition could be reversed by the addition of human recombinant IL-2 (hrIL-2). The stimulation of IL-2 production induced by human colostrum might compensate for its inhibitory effect on NK cell activity. These findings suggest an additional mechanism by which breast feeding may affect the neonatal immune system.

Colostrum↗

Phagocytosis-promoting factor in human colostrum.

The effect of colostrum of mothers of preterm and full-term newborns on the phagocytic activity for latex particles by normal peripheral blood polymorphonuclear cells was examined. The results showed that human colostrum contains a phagocytosis-promoting factor(s), which not only increases the number of phagocytic cells, but also stimulates the phagocytic activity of the individual cell. This factor(s) was more active in preterm colostrum. Thus, while term colostrum increased the number of phagocytic cells by 95% in comparison with the control, preterm colostrum enhanced the number of phagocytic cells by 300%. Similarly, term colostrum increased the phagocytic capacity of the individual cell by 51%, whereas preterm colostrum by 137%. The difference between the results in all experimental points was statistically highly significant.

Blood Proteins↗

Effect of three intravenously administered fat emulsions containing different concentrations of fatty acids on the plasma fatty acid composition of premature infants.

The effects of an intravenously administered lipid emulsion supplemented with gamma-linolenic acid on the fatty acid profile of premature infants were compared with those of two conventional lipid emulsions. Fifty-nine premature neonates receiving total parenteral nutrition were randomly assigned to receive either fat emulsion containing gamma-linolenic acid and long-chain triglycerides (LCT), an LCT emulsion, or a 50% (wt/wt) mixture of medium-chain triglycerides and LCT emulsion. Forty-nine infants completed the study. During the 6-day study there was a significant tenfold increase in the plasma levels of gamma-linoleic acid in the supplemented group versus the other two groups. A significant threefold to fivefold increase in the omega 6 long-chain polyunsaturated fatty acids was observed in all groups. These changes seemed to be attributable mostly to linoleic acid from the lipid emulsion, despite the 50% lower dose in the medium- and long-chain triglycerides group. The increase in the omega 3 long-chain polyunsaturated fatty acids also was mainly caused by a similar increase in the level of alpha-linolenic acid. No differences were recorded in the linoleic/alpha-linolenic acid ratio among the groups. Plasma levels of some of the semiessential fatty acids were significantly higher in the medium- and long-chain triglycerides group than in the LCT group. This may be related to slower elimination of LCT, to the difference between emulsions, or to less substrate inhibition on delta-6-desaturase, which seems to be less of a rate-limiting enzyme than previously considered. Further intravenous feeding trials are needed to identify the optimal balance of fatty acids for nutrition of these premature infants.

Double-Blind Method↗

Alpers progressive infantile neuronal poliodystrophy: an acute neonatal form with findings of the fetal akinesia syndrome.

We report on 8 patients from two families with Alpers syndrome. The onset in one family was prenatal and in the 4 patients who were examined, severe microcephaly, intrauterine growth retardation, and typical manifestations of fetal akinesia, including retrognathia, joint limitations, and chest deformity were found. The second family presented with an early infantile form. All the affected offspring had micrognathia and one had findings of fetal akinesia, comparable to those seen in the other family. Microcephaly was mild at birth and progressed with age. Refractory neonatal convulsions, swallowing difficulties, and pneumonia complicated the clinical course of patients in both families, and all the patients died before age 20 months. Results of comprehensive biochemical and metabolic studies in both families were normal and the diagnosis was supported by demonstration of extensive progressive brain atrophy on CT and typical histological findings. Patients without a detectable defect in energy metabolism and normal liver histology comprise a distinct subset of Alpers syndrome. Until the metabolic defect(s) is defined, we suggest naming the acute neonatal form of this subset of Alpers syndrome "type 1."

Abnormalities, Multiple↗

IL-1 beta and IL-3-like activity in preterm infants.

The capacity of peripheral blood mononuclear cells (PBMC) of preterm neonates to release IL-1 beta and IL-3-like activity (IL-3-LA) has been investigated. In the present study it was found that this capacity is significantly lower than that of their mothers and of control adults. In addition, the results showed that preterm serum has a lower stimulatory effect on IL-1 beta production and an inhibitory effect on IL-3-LA secretion by PBMC of adult controls, in comparison with maternal and adult sera. These findings suggest an additional feedback mechanism for control of haematopoiesis in premature neonates. It is possible that the lower production of IL-1 beta and IL-3-LA may be involved in the increased susceptibility to infections of preterm newborns.

Adult↗

IL-2 receptor gene expression and IL-2 production by human preterm newborns' cells.

IL-2 receptor (IL-2R) gene expression in human umbilical cord blood mononuclear cells (CBMC) of preterm and term newborns was examined following stimulation for 18 h with phytohaemagglutinin (PHA) and compared with that of adult peripheral blood mononuclear cells (PBMC; mothers and control group). mRNA for IL-2R could not be detected in CBMC of preterm infants, whereas the mRNA levels for IL-2R found in full term neonates were similar to those observed in PBMC of adults. IL-2 activity in conditioned medium (CM) of mononuclear cells stimulated with either optimal or suboptimal PHA concentrations for 24 h and 48 h was also determined. At 24 h of stimulation, IL-2 activity found in CM obtained from CBMC of preterm and term newborns was significantly higher than that found in CM of adults' PBMC. A further enhancement of IL-2 activity (six to eight times) was observed in CM of preterm and term cells stimulated for 48 h, whereas no significant difference was found in IL-2 activity in CM from adult cells tested at the two incubation periods. The present findings may provide an additional explanation for the impaired function of the immune system, and the high susceptibility to infections observed in preterm newborns.

Cells, Cultured↗

Beta glucuronidase and hyperbilirubinaemia in breast fed infants of diabetic mothers.

A prospective study was performed comparing bilirubin concentrations in 10 breast fed term infants of diabetic mothers (IDM) to those of 10 breast fed normal term infants. The beta-glucuronidase concentrations in serum and breast milk were assayed in the respective mothers. Significantly higher bilirubin concentrations were noted in the IDM group. Serum and breast milk beta-glucuronidase concentrations were significantly higher in diabetic mothers as compared with those of non-diabetic mothers. We suggest that the high concentration of beta-glucuronidase in breast milk of diabetic mothers is an additional important cause leading to hyperbilirubinaemia in their breast fed infants.

Bilirubin↗

Genital mycoplasmas in preterm infants: prevalence and clinical significance.

The genital mycoplasmas: Ureaplasma urealyticum and Mycoplasma hominis have recently assumed an increasing importance as neonatal pathogens. The aim of the present survey was to determine the prevalence of infections with these organisms in preterm infants in two neonatal intensive care units in Israel. Among 99 preterm infants, 24 (24%) harboured mycoplasmas in their throats shortly after birth. U. urealyticum was the most common organism. M. hominis was isolated only from 3 infants. Six out of 27 (22%) mechanically ventilated infants secreted U. urealyticum in their lower airways. The rate of colonization was inversely correlated with gestational age; 80% of infants younger than 28 weeks gestation were found to be colonized as opposed to 17.9% at 28-36 weeks of gestation. No mycoplasmas were isolated in blood cultures drawn from 146 infants and CSF cultures obtained from 47 preterm infants. Neonatal mortality, respiratory complications and intraventricular haemorrhage grade 3-4 were significantly increased in colonized infants. However, above gestational age of 27 weeks, colonization with mycoplasmas was not associated with a worse prognosis. We conclude that colonization with U. urealyticum is common in Israeli preterm infants, correlates inversely with gestational age and has no detrimental effect on neonatal morbidity and mortality of infants older than 27 wks of gestation.

Genitalia↗

Schizophrenia and Marfan syndrome.

Five index patients and three of their first-degree relatives were affected both by schizophrenia and Marfan syndrome. Since the association appears statistically significant, the possibility of linkage disequilibrium between adjacent genes or a cytogenetic abnormality causing both disorders is suggested. These hypotheses are testable and hold promise in attempting to map the 'schizophrenia susceptibility gene' by the candidate-gene approach.

Adult↗

Radiological colpocephaly: a congenital malformation or the result of intrauterine and perinatal brain damage.

The term colpocephaly, meaning disproportional enlargement of the occipital horns of the lateral ventricles, was considered in the past to be a distinct congenital malformation acquired in early intrauterine life. During the last few years several cases were reported in whom a variety of intrauterine and perinatal causes could be associated with this radiological picture. We report on 9 children with radiological colpocephaly in whom intrauterine and/or perinatal injury to the developing brain seemed to be the cause of colpocephaly. It is evident from our observations that "radiological colpocephaly" is a non-specific finding caused frequently by CNS damage acquired during intrauterine and perinatal life.

Brain Diseases↗

Role of the newborn's sex in mixed maternal-newborn lymphocyte culture reactivity.

One-way-stimulated mixed mother-newborn lymphocyte cultures (MMNLC) from male and female newborns were evaluated and compared shortly after delivery. Newborn sex-correlated differences were observed in the strength of the MMNLC reactivity with responding maternal as well as newborn cells. The reactivity of MMNLC with responding maternal cells from male as compared to female newborns was significantly less inhibited in maternal and newborn serum. The inhibitory effect of maternal serum on maternal and male newborn lymphocytes in MMNLC seems to be correlated to the sex of the previous child delivered and was significantly lower when the present as well as the previous baby were of the same sex, e.g. 2 boys. The results suggest that fetal-male-specific Y-chromosome-correlated histocompatibility antigens may specifically influence the maternal immune response to her fetus.

Female↗

Placental isoferritin as a physiological downregulator of cellular immunoreactivity during pregnancy.

CM-H-9 monoclonal antibody specific for placental isoferritin (PLF) was used to quantify PLF in the serum and on peripheral blood lymphocytes derived from term delivery women and healthy controls. It was found that the mean level of PLF in maternal sera was 50.4 +/- 50.1 U/ml, whereas in normal adults the mean serum PLF level was very low (4.5 +/- 7.7 U/ml). Furthermore, term mothers exhibited a sub-population of peripheral blood lymphocytes (PBL) which stained positively with CM-H-9 MoAb (mean 11.6 +/- 7.8%). Such lymphocytes were scarce in normal non-pregnant women (mean 0.8 +/- 1.2%). The effect of PLF on lymphocyte transformation in MLC was studied in mixed lymphocyte cultures of maternal-newborn and normal non-related PBL controls. It was found that placental isoferritin was immunosuppressive in comparison to normal adult ferritin. The suppressive effect was significantly higher in maternal-newborn MLC compared to normal adult controls. Furthermore, it was found that PLF which is present in maternal serum has an immunosuppressive activity since, its removal on CM-H-9 MoAb affinity column abrogated this effect. The results of this study suggest that both PLF and PLF binding lymphocytes play a role in the development of immunosuppression during pregnancy. Therefore the lack of one of the factors may result in diminished immunosuppression or in fetal rejection.

Female↗