Contact allergy in relation to hand eczema and atopic diseases in north Norwegian schoolchildren

Dotterud LK, Falk ES. Contact allergy in relation to hand eczema and atopic diseases in north Norwegian schoolchildren. Acta Psediatr 1995;84:402–6. Stockholm. ISSN 0803–5253
Patch testing was carried out in 424 schoolchildren (223M, 201F), aged 7–12 years, in northern Norway. In 99 (23.3%) of these children, one or more allergic patch test reactions were demonstrated; 30 children reacted to two and 6 to three or more substances; 53 irritant reactions were recorded in 33 (7.8%) of those tested. From a total of 144 positive tests, the most common allergen was nickel (14.9%), followed by cobalt (5.7%), kathon CG (5.2%), lanolin (1.7%) and neomycin (1.4%). Both allergic and irritant reactions were found twice as frequently in girls as in boys. Positive patch tests were significantly more frequent in atopic (28.8%) than in non–atopic (17.9%) children, being most pronounced in atopic girls (37.4%). Hand eczema was reported to have occurred or to be present in 6.5% of cases. Twenty–nine of 36 children reporting hand eczema participated in the clinical examination. Altogether 15 (3.5%) children had hand eczema at the time of the clinical examination but 12 of these children had no previous history of hand eczema. In 14 of these 15 subjects, the eczema was localized to the back of the hands, with 13 having atopic dermatitis. In 4 of these 15 children, an allergic patch test reaction was found; however, in only 2 of these 4 was the test considered to be clinically relevant for the diagnosis allergic hand eczema. In conclusion, irritant hand eczema may occur in early childhood and is most prevalent in children with atopic dermatitis     

Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate

We observed that pretreatment of male F344 rats with benzyl selenocyanate, a versatile organoselenium chemopreventive agent in several animal model systems, decreases the levels of DNA and RNA modifications produced in the liver by the hepatocarcinogen 2- nitropropane. To clarify the mechanisms involved, we pretreated male F344 rats with either benzyl selenocyanate, its sulfur analog benzyl thiocyanate, phenobarbital or cobalt protoporphyrin IX; the latter is a depletor of P450. We then determined (1) the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on 2-nitropropane- induced liver DNA and RNA modifications and (3) amount of nitrate excreted in rat urine following administration of the carcinogen. Pretreatment with benzyl selenocyanate or phenobarbital increased the denitrification activity of liver microsomes by 217 and 765%, respectively, increased liver P4502B1 by 31- and 435-fold, respectively, decreased the levels of 2-nitropropane-induced modifications in liver DNA (29-70% and 17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and increased the 24-h urinary excretion of nitrate by 157 and 209%, respectively. Pretreatment with benzyl thiocyanate had no significant effect on any of these parameters. Pretreatment with cobalt protoporphyrin IX decreased liver P4502B 1 by 87%, decreased the denitrification activity of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic acid modifications by 17-67%. These results indicate that the metabolic sequence from 2-nitropropane to the reactive species causing DNA and RNA modifications does not involve the removal of the nitro group. Moreover, they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic acid modifications in part by increasing its detoxication through induction of denitrification, although it is evident that other mechanisms must also be involved.      

Granulocyte colony-stimulating factor crosses the placenta and stimulates fetal rat granulopoiesis

We studied the effect of recombinant human granulocyte colony- stimulating factor (rhG-CSF) administration to pregnant rats upon fetal and neonatal myelopoiesis. Pregnant rats were treated with rhG-CSF twice daily for 2, 4, and 6 days before parturition. rhG-CSF crossed the placenta and reached peak fetal serum concentrations 4 hours after administration. Peak fetal serum levels were 1,000-fold lower than levels detected in the dam. Hematopoietic effects of rhG-CSF were assessed by cytologic analysis of the newborn blood, spleen, bone marrow, thymus, and liver. White blood cell counts were increased twofold to fourfold in newborns. This increase was due to circulating numbers of polymorphonuclear cells (PMN). rhG-CSF induced a myeloid hyperplasia in the newborn marrow consisting of immature and mature myeloid cells in the day-2 and day-4 treated pups. Bone marrow of pups treated for 6 days contained mostly hyper-segmented PMN with little or no increase in myeloid precursors. An increase in the number of postmitotic (PMN, bands, and metamyelocytes) and mitotic (promyeloblasts, myeloblasts, and metamyeloblasts) myeloid cells in the spleen of neonates was observed. No change was detected in splenic lymphocytes or monocytes. No effect of rhG-CSF was noted in the newborn liver or thymus. These results demonstrate that maternally administered rhG-CSF crosses the placenta and specifically induces bone marrow and spleen myelopoiesis in the fetus and neonate. The significant myelopoietic effects of rhG-CSF at low concentrations in the fetus suggest an exquisite degree of developmental sensitivity to this cytokine and may provide enhanced defense mechanisms to the neonate.     

Primary Bile Duct Stones and Bacterial Activity

The results of this study suggest that infection with beta-glucuronidase active bacteria is the initial event in the nucleation of primary bile duct stones (PBDS).PBDS from five patients were morphologically fragile and “earthy” with alternating light and dark brown pigment layers with no evidence of a distinct central nucleus that may have been reminiscent of a different structure. Chemically, calcium bilirubinate and calcium palmitate were prominent throughout their structure. All bile duct biles had a positive culture and were always associated with at least one bacterial species which was beta-glucuronidase active. Moreover, fragments of PBDS nuclear areas had positive cultures that were comparable with those present in their individual bile duct bile. Microscopic examination of bile showed abundant precipitation of calcium bilirubinate granules in all samples.Thus, bile duct bile infection with beta-glucuronidase active bacteria (e.g. E. coli, C. perfringens) appears to be a key factor in PBDS pathogenesis, having a precursor role, rather than being a consequence. Bile stasis is likely to be a co-factor which must have a supportive role in subsequent stone growth.     

A soluble, high-affinity, interleukin-4-binding protein is present in the biological fluids of mice.

Cytokines such as interleukin 4 (IL-4) play a key role in the regulation of immune responses, but little is known about how their multiple activities are regulated in vivo. In this report, we demonstrated that an IL-4-binding protein (IL-4BP) is constitutively present in the biological fluids of mice (serum, ascites, fluid, and urine). Binding of 125I-labeled IL-4 to the IL-4BP is specific and saturable and can be inhibited by an excess of unlabeled IL-4 but not IL-2. The IL-4BP binds IL-4 with an affinity similar to that reported for the cellular IL-4 receptor (Kd approximately 7 x 10(-11) M) and has a molecular mass of 30-40 kDa and pI values of 3.6-4.8. IL-4BP-containing biological fluids or purified IL-4BP competitively inhibit the binding of 125I-labeled IL-4 to mouse T or B cells and inhibit the biological activity of IL-4 but not IL-2. The serum levels of IL-4BP in severe combined immunodeficiency (SCID) mice are lower than those of normal mice. The above findings suggest that IL-4BP plays an important immunoregulatory role in vivo.     

Serum levels of beta-carotene, vitamin A, and zinc in male lung cancer cases and controls

The mean serum levels of beta-carotene and vitamin A in a multivariate analysis of data from 64 histologically confirmed male lung cancer cases were statistically significantly lower than those from 63 randomly selected male hospital controls, who were admitted for small surgical operations (p values for both beta-carotene and vitamin A less than 0.001). The mean serum levels of zinc were not statistically significantly different between cases and controls (p = 0.10). The levels of beta-carotene, vitamin A, or zinc were not statistically significantly influenced by either the extent of the cancer (p = 0.45) or the cancer cell type (p = 0.06). The possible biological significance of these findings is discussed briefly.     

Antitumor activity of Fab' and IgG-anti-CD22 immunotoxins in disseminated human B lymphoma grown in mice with severe combined immunodeficiency disease: effect on tumor cells in extranodal sites

The antitumor effects of two anti-CD22 ricin A chain-containing immunotoxin (IT) constructs were compared in mice with severe combined immunodeficiency disease with human Daudi cell tumors (SCID-Daudi mice). SCID-Daudi mice develop disseminated lymphoma that clinically resembles African Burkitt's lymphoma, i.e., extranodal disease including infiltration of the vertebral column and spinal canal. In the absence of treatment, the mean survival time of SCID-Daudi mice was 45.9 +/- 4.3 days. The mice was given injections of a dose of IT equal to 40% of the 50% lethal dose. The ITs consisted of either IgG or Fab' fragments of mouse anti-CD22 antibody coupled to deglycosylated ricin A chain (dgA). Both ITs were potent and specific and inhibited protein synthesis in Daudi cells in vitro by 50% at concentrations of 1.2 x 10(-12) (IgG-dgA) and 1.3 x 10(-11) M (Fab'-dgA). When administered to mice beginning 1 day after inoculation with tumor cells, both ITs extended the mean survival time, to 87.2 +/- 18.9 days (IgG-dgA) or 57.9 +/- 3.8 days (Fab'-dgA). The latter represented the killing of 2 logs of Daudi cells, and the former 4 logs. IgG antibody alone killed 1 log of tumor cells. The IgG-dgA had an antitumor effect even when administered 20-23 days after tumor inoculation. Gross and histological examinations of IT-treated tumor-bearing mice showed a marked decrease in the number and size of neoplastic foci in both lymphoid organs and extranodal sites.