Preseasonal intranasal immunotherapy in birch-alder allergic rhinitis. A double-blind study

A double-blind, placebo-controlled study was carried out to test the clinical efficacy and safety of local nasal immunotherapy (LNIT) in powder form. Twenty-two patients suffering from allergic rhinitis strictly associated with early spring symptoms, with positive skin prick tests and RAST for birch-alder, all responders to a specific nasal provocation test (NPT), received randomly active or placebo treatment for 4 months. Immunotherapy consisted of administration of a set of capsules containing progressively increasing amounts of birch (Betula pendula) and speckled alder (Alnus incana) allergens in powder form with controlled granulometry. The active (birch-alder) and placebo (lactose) group completed the treatment according to a similar schedule. During the pollen season (March-April), the patients who took the active treatment reported less sneezing and rhinorrhea than the placebo group, on the basis of a symptoms score, and the differences were statistically significant; the need for drugs (terfenadine) was also significantly reduced. These findings agreed well with the results of specific NPT after the treatment; only patients in the active group had a higher threshold dose of nasal specific reactivity to birch-alder allergens than in tests before the LNIT.     

Venous and arteriovenous vascular malformations: diagnostic and therapeutic considerations regarding 239 patients observed in the 1978-1991 period

Substitution enterocystoplasty is becoming more common in a selected group of patients. Acute or chronic ischemia is an exceptional event. We describe the clinical manifestations and management of chronic ischemia of a neobladder that occurred weeks after a successful initial operation. The possible mechanisms responsible for this complication are reviewed.     

Transfer of a supernumerary chromosome between vegetatively incompatible biotypes of the fungus Colletotrichum gloeosporioides

Two biotypes (A and B) of Colletotrichum gloeosporioides infect the tropical legumes Stylosanthes spp. in Australia. These biotypes are asexual and vegetatively incompatible. However, field isolates of biotype B carrying a supernumerary 2-Mb chromosome, thought to originate from biotype A, have been reported previously. We tested the hypothesis that the 2-Mb chromosome could be transferred from biotype A to biotype B under laboratory conditions. Selectable marker genes conferring resistance to hygromycin and phleomycin were introduced into isolates of biotypes A and B, respectively. A transformant of biotype A, with the hygromycin resistance gene integrated on the 2-Mb chromosome, was cocultivated with phleomycin-resistant transformants of biotype B. Double antibiotic-resistant colonies were obtained from conidia of these mixed cultures at a frequency of approximately 10(-7). Molecular analysis using RFLPs, RAPDs, and electrophoretic karyotypes showed that these colonies contained the 2-Mb chromosome in a biotype B genetic background. In contrast, no double antibiotic colonies developed from conidia obtained from mixed cultures of phleomycin-resistant transformants of biotype B with biotype A transformants carrying the hygromycin resistance gene integrated in chromosomes >2 Mb in size. The results demonstrated that the 2-Mb chromosome was selectively transferred from biotype A to biotype B. The horizontal transfer of specific chromosomes across vegetative incompatibility barriers may explain the origin of supernumerary chromosomes in fungi.     

Childhood leukemia in Belarus before and after the Chernobyl accident

Childhood leukemia (ICD 204-208 [1]) incidence rates in the different regions of Belarus are reported for a period before and after the Chernobyl accident (1982-1994). There are, at this point, no recognizable trends towards higher rates.     

Experience in the study of the effects of lead on the health status of children in Belovo]

Lead releases in Belovo town containing metallurgy enterprise had reached 120 tons/year earlier, but in recent years have decreased to 9 tons/year. Reduction of the production induced decrease of lead levels in the ambient air from 0.7-2.3 mg/m3 in 1994 to 0.001-0.24 mg/m3. Lead concentration in the soil ranges from 30 to 3000 mg/kg. Lead levels were measured in serum of 91 children, in hair of 67 ones and in teeth of 15 children. Serum lead levels in children aged 7-8 years varied from 0.5 to 39 mg/dl, with an average of 9.9 mg/dl (SD is 5.2 mg/dl), geometric mean is 8.5 mg/dl and error of geometric mean is 3.3. 46% of the children had serum lead levels exceeding the normal one (10 mg/dl). Average lead level in the hair equaled 4.5 mg/g (SD is 4.9 mg/g). The children living in towns with higher environmental lead levels demonstrated more frequent anxiety and changes in higher psychic functions. The major points influencing the serum lead level are proximity to highway, dietary load of goods grown near the residence, mother's smoking. Biokinetic model describing lead transfer into the blood helped to evaluate various modes of the enterprise functioning and efficiency of some environmental protection measures. The most efficient are measures aimed to lower dietary intake of lead, less efficiency is associated with measures reducing lead levels in air, dust and soil.     

Characterization of benzo[a]pyrene-initiated mouse skin papillomas for Ha-ras mutations and protein kinase C levels

The frequency and spectrum of Ha-ras mutations in benzo[a]pyrene (B[a]P)-initiated/12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted CD-1 mouse skin papillomas were characterized by amplifying high molecular weight papilloma DNA using the polymerase chain reaction (PCR) followed by direct DNA sequencing. Analysis of 10 individual B[a]P-initiated early emergence papillomas indicated that 90% contained a Ha-ras mutation. Twenty percent of these papillomas contained a GGA-->GTA transversion in the 12th codon, 50% contained a GGC-->GTC transversion in the 13th codon and 20% contained a CAA-->CTA transversion in the 61st codon. A characteristic of 7,12-dimethylbenz[a]anthracene (DMBA)-initiated papillomas, which contain an A-->T mutation in the 61st codon of Ha-ras, is that they exhibit a constitutive decrease in both protein kinase C (PKC) activity and PKC alpha and beta 2 isozyme levels when compared to epidermis. In the present study we found that total PKC activity, as well as PKC alpha and beta 2 isoforms, were markedly decreased in B[a]P-initiated early emergence papillomas and that this decrease was also accompanied by an altered subcellular distribution of PKC activity. The particulate/cytosolic (P/C) ratio of PKC activity in the epidermis was 0.39, whereas the P/C ratio in the papillomas was 0.77. These results demonstrate that B[a]P-initiated/TPA-promoted papillomas exhibit a high incidence of specific ras mutations and that PKC levels are constitutively decreased in these papillomas, indicating that an activated ras gene is associated with and may contribute to the observed decrease in PKC levels.     

The crystallographic structure of the protease from human immunodeficiency virus type 2 with two synthetic peptidic transition state analog inhibitors

The crystal structure of human immunodeficiency virus (HIV) type 2 protease has been determined in complexes with peptidic inhibitors Noa-His-Cha psi [CH(OH)CH(OH)]Val-Ile-Amp (U75875) and Qnc-Asn-Cha psi [CH(OH)CH2]Val-Npt(U92163) (where Noa is naphthyloxyacetyl, Cha is cyclohexylalanine, Amp is 2-aminomethylpyridine, Qnc is quinoline-2-carbonyl, and Npt is neopentylamine), which have dihydroxyethylene and hydroxyethylene moieties, respectively, in place of the normal scissile bond of the natural ligand. The complexes crystallize in space group P2(1)2(1)2(1), with one dimer-inhibitor complex per asymmetric unit and average cell dimensions of a = 33.28 A, b = 45.35 A, c = 135.84 A. Data were collected to approximately 2.5-A resolution. The model structures were refined with resulting R-factors of around 0.19. As expected, the HIV-2 protease structure is approximately C2-symmetric with a gross structure very similar to that of the HIV-1 enzyme. The inhibitors bind in an extended conformation positioned lengthwise in the binding cleft in a manner similar to that found in the HIV-1 protease-inhibitor complexes previously reported. The substitution of the bulkier Ile82 side chain in the HIV-2 protease may help explain the better ability of HIV-2 protease to bind and hydrolyze ligands with small P1 and P1' side groups. It appears that differences in specificity between the proteases of HIV-1 and HIV-2 are not merely a result of simple side chain substitutions, but may be complicated by differences in main chain flexibility as well.     

Toxicity of L-ascorbic acid to L929 fibroblast cultures: relevance to biocompatibility testing of materials for use in wound management

Fibroblast cultures are often used to evaluate materials intended for medical use, cytotoxicity being taken as an indicator of bioincompatibility. Such an approach has previously been taken with ascorbic acid in determining its value in wound healing. We have now reexamined the toxicity of L-ascorbic acid to L929 fibroblast cells in culture. Concentrations of ascorbic acid between 0.5 mM and 11 mM were tested. At concentrations above 2 mM, ascorbic acid was found to inhibit cell proliferation, with cell viability decreasing as the concentration was increased. This effect could be prevented by the addition of either superoxide dismutase or catalase to the culture medium. Assays of glutathione and glutathione disulfide were carried out on 8 day old cultures exposed for 24 h to the same concentrations of ascorbic acid. A dose-related depletion of glutathione occurred whilst glutathione disulfide levels remained essentially constant. Lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities were induced by ascorbic acid at all concentrations tested but the ratio of NADP to NADPH nevertheless increased as the concentration of ascorbic acid increased. Finally, ATP in cells from 8-day-old cultures became depleted in the presence of ascorbic acid at concentrations in excess of about 5 mM when assayed after 24 h incubation. These biochemical changes and the concomitant cytostatic/cytotoxic effects may be ascribed to the reactive oxygen species produced by the autoxidation of ascorbic acid in the culture medium. Ascorbic acid breakdown products appeared not to be directly involved. In addition, our results suggested that superoxide acted cooperatively with hydroxyl to elicit these effects on the fibroblasts. It is evident from this study that the microenvironment surrounding fibroblasts in culture may differ fundamentally from that surrounding fibroblasts in a healing wound, making it impossible to extrapolate directly to an in vivo situation and hence to make any recommendations from these results concerning the use of ascorbic acid in wound healing.