Dimethylthiourea inhibition of melanoma cell growth in vitro and in vivo.

The effect of dimethylthiourea (DMTU), an agent known as a hydroxyl radical scavenger, was determined on growth and differentiation of the B16 murine melanoma cell line. DMTU inhibited melanoma cell growth in vitro and induced changes in the morphology of melanoma cells. Prolonged treatment of cells with DMTU resulted in an increase in melanin content. DMTU-treated melanoma cells had a decreased capacity to form tumors in syngeneic mice. Systemic administration of DMT to C57BL/6J mice inoculated with melanoma cells resulted in a delay in tumor appearance and a prolongation of survival. The doses of DMTU used did not cause any apparent toxic effects. A potential therapeutic role for DMTU in the treatment of melanoma is suggested.

Normal pulmonary function in a monoamniotic twin discordant for bilateral renal agenesis: report and review.

Renal agenesis and obstructive urinary tract anomalies causing oligohydramnios usually result in pulmonary hypoplasia. We report on the first female monoamniotic twin born with a combination of bilateral renal agenesis, agenesis of the urinary collecting system, absent external genitalia, anal atresia and single umbilical artery, compatible with VATER association but with normal pulmonary function. The infant had none of the manifestations of Potter sequence, in particular the facial changes and pulmonary hypoplasia typically associated with bilateral renal a/dysgenesis. The monoamniotic cotwin had normal renal function, such that sufficient amniotic fluid volume was maintained. This patient emphasizes the importance of adequate amniotic fluid volume for normal pulmonary development. The possible underestimation of genital malformations in the VATER association should be considered. Also noteworthy is the rare absence of external genitalia.

Effect of cefotaxime on cytokine production in newborns and adults in vitro.

The in vitro effect of cefotaxime on the production of interleukin (IL)-1beta, IL-2, IL-6 and tumor necrosis factor alpha (TNFalpha) was studied in term neonates and was compared with that of adults. The addition of cefotaxime caused a significant enhancement of IL-2 production by cells of both adults and neonates, and increased the secretion of TNFalpha by peripheral blood mononuclear cells (PBMC) of adults, whereas the synthesis of this cytokine by cord blood mononuclear cells (CBMC) of the newborns was not affected. In contrast with the described stimulatory effects of cefotaxime, this drug induced dose-dependent inhibition of the spontaneous and lipopolysaccharide (LPS)-induced IL-1beta production by cells of the two groups, but had no effect on the in vitro production of IL-6. These data suggest that cefotaxime, apart from its known antimicrobial activity, may modify the host immune response of both newborns and adults, via the alteration of cytokine production.

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.

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.

Effect of physical effort on the white blood cells in benign familial leukopenia.

The components of the peripheral white blood cells (WBC) were determined before and after 10 min of submaximal ergometric work in two groups of subjects: 34 healthy Yemenite Jews with benign familial leukopenia (BFL) and 34 healthy Yemenite Jews without BFL. The mean +/- SEM of the increase in the peripheral WBC following the effort in the control group was 2,606 +/- 1,272 cells/mm3, due to the relative rise in the neutrophils, eosinophils, monocytes and lymphocytes. The identical ergometric work, performed by BFL subjects, brought about significantly lower increase (700 +/- 865 cells/mm3) in the peripheral WBC, the majority of which were lymphocytes. It seems that subjects with this form of BFL lack granulocytes in the marginal pool.

Effects of dexamethasone on IL-1beta, IL-6, and TNF-alpha production by mononuclear cells of newborns and adults.

The effects of dexamethasone on the production of interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha were studied in preterm newborns, term infants, and adults. Twenty preterm and 22 term newborns and 30 healthy adults were included in the study. Mononuclear cells (MC) isolated from cord blood of newborns and peripheral blood of adults were incubated without or with lipopolysaccharide in the absence or presence of dexamethasone at concentrations between 10(-8) and 10(-5) M. The cytokine concentration in the supernatants was tested using enzyme-linked immunosorbent assay kits. Although a dose-dependent inhibition of the cytokine production was observed at pharmacological doses of dexamethasone in individuals of the three groups, differences in the intensity of the effect were observed between the groups. Spontaneous secretion of IL-1beta or IL-6 by MC of preterm neonates was less inhibited by dexamethasone as compared with cells from adults. In contrast, the inhibitory effect of the drug on lipopolysaccharide-induced IL-6 and tumor necrosis factor alpha production was more pronounced on neonatal cells. As for term newborns, MC were more sensitive to the inhibitory effect of the drug on LPS-induced IL-6 production than cells of adults. The results suggest that dexamethasone treatment of preterm newborns may affect cytokine production with a consequent modulation of the host's immune response.

Phototherapy for neonatal hyperbilirubinemia affects cytokine production by peripheral blood mononuclear cells.

The capacity of peripheral blood mononuclear cells (PBMC) to produce interleukin (IL) IL-1beta, IL-2, IL-3, IL-6, IL-10 and tumor necrosis factor-alpha (TNFalpha) was examined in term newborns with hyperbilirubinemia after 24 hours' exposure to phototherapy (wave length 425-475 nm). The results were compared with those from untreated neonates. Fifty newborns spontaneously delivered at term were included in the study. Blood samples were collected from 20 newborns before and 24 h after phototherapy. The control group consisted of 30 neonates examined on two consecutive days. PBMC isolated from blood samples were incubated in vitro for cytokine production. The concentration of cytokines in the supernatants was tested using ELISA kits (for IL-1beta, IL-6, IL-10 and TNFalpha), or by bioassays (for IL-2 and IL-3). Phototherapy caused a 70% increase in IL-2 secretion (123 +/- 27 vs 208 +/- 30 units/ml, P < 0.01) and 56% in IL-10 production (1.07 +/- 0.19 vs 1.67 +/- 0.33 ng/ml, P < 0. 03), whereas the spontaneous secretion of IL-1beta was reduced by 43% (13.7 +/- 2.3 vs 7.3 +/- 1.7 ng/ml, P < 0.02). In the control group the secretion of these cytokines was similar on the two consecutive days and did not differ significantly from secretion in the other group before phototherapy. On the other hand, lipopolysaccharide induced TNFalpha production was higher on the second day in the two groups of newborns irrespective of phototherapy (388 +/- 58 vs 683 +/- 88 pg/ml, P < 0.001, in the control group and 384 +/- 75 vs 588 +/- 91, P < 0.05, before and after phototherapy). The synthesis of IL-3 and IL-6 did not change significantly between the two days of the study. The results demonstrate that in addition to the well-known positive effect of phototherapy on the neonate serum bilirubin level, this treatment affects the function of the immune system in newborns via alterations in cytokine production.

Lymphocyte subpopulations in mother and newborn: correlation with sex of the newborn and number of pregnancies.

T cell subsets were defined with monoclonal antibodies of the OKT series, OKT3, OKT4 and OKT8, in 23 male and 22 female newborns and in their mothers 4-10 h after delivery. The data were compared and statistically evaluated between mother and newborn, between male and female newborns as well as between parity groups. The results indicate that the distribution of OKT4 and OKT8+ cells is different in mother and newborn and a significantly increased percentage of OKT4+ cells and a significantly decreased percentage of OKT3+ cells was observed in newborns as compared to their mothers after the first and second delivery. For maternal cells from male as compared to female newborns the percentage of OKT4+ was significantly decreased after the second delivery. OKT8+ cells in the mother were significantly decreased after the second as well as after three or more deliveries of male as compared to female newborns. With increasing parity the percentage of OKT3+, OKT4+ and OKT8+ cells decreased slowly for both sexes and the difference was significant between primi- and multiparae. The present findings suggest a possible role of the newborn sex and of parity in the distribution of specific T cell subsets in mother and newborn shortly after delivery.

Growth inhibition of murine melanoma by butyric acid and dimethylsulfoxide.

Treatment of B16-F10 melanoma cells with dimethylsulfoxide (DMSO) or butyric acid (BA) inhibits cell growth and delays tumor appearance in syngeneic mice. Both agents induce morphological changes in these cells. Treatment of melanoma cells with DMSO results in a marked increase in tyrosinase activity and melanin content. BA, on the other hand, does not increase melanin content and decreases tyrosinase activity. The data show that there are marked differences in the effect of DMSO and BA on melanin biosynthesis, whereas both agents inhibit cell growth and cause a delay in tumor appearance. These findings indicate that decreased proliferation of melanoma cells and induction of melanin biosynthesis are not necessarily associated phenomena.