Mutations in the SLC35C1 gene, contributing to significant differences in fucosylation patterns, may underlie the diverse phenotypic manifestations observed in leukocyte adhesion deficiency type II patients.

Congenital disorders of glycosylation (CDG) are a large family of genetic diseases resulting from defects in the synthesis of glycans and the attachment of glycans to macromolecules. The CDG known as leukocyte adhesion deficiency II (LAD II) is an autosomal, recessive disorder caused by mutations in the SLC35C1 gene, encoding a transmembrane protein of the Golgi apparatus, involved in GDP-fucose transport from the cytosol to the Golgi lumen. In this study, a cell-based model was used as a tool to characterize the molecular background of a therapy based on a fucose-supplemented diet. Such therapies have been successfully introduced in some (but not all) known cases of LAD II. In this study, the effect of external fucose was analyzed in SLC35C1 KO cell lines, expressing 11 mutated SLC35C1 proteins, previously discovered in patients with an LAD II diagnosis. For many of them, the cis-Golgi subcellular localization was affected; however, some proteins were localized properly. Additionally, although mutated SLC35C1 caused different α-1-6 core fucosylation of N-glycans, which explains previously described, more or less severe disorder symptoms, the differences practically disappeared after external fucose supplementation, with fucosylation restored to the level observed in healthy cells. This indicates that additional fucose in the diet should improve the condition of all patients. Thus, for patients diagnosed with LAD II we advocate careful analysis of particular mutations using the SLC35C1-KO cell line-based model, to predict changes in localization and fucosylation rate. We also recommend searching for additional mutations in the human genome of LAD II patients, when fucose supplementation does not influence patients' state.

Early alveolar bone grafting has a negative effect on maxillary dental arch dimensions of pre-school children with complete unilateral cleft lip and palate.

OBJECTIVE: To evaluate maxillary dental arch dimensions in pre-school children with a complete unilateral cleft lip and palate (CUCLP) after early alveolar bone grafting. MATERIAL AND METHODS: Intercanine and intermolar widths, length of dental arch and mesiopalatal inclination of both maxillary segments were measured directly on the dental casts of 42 children (27 boys and 15 girls; mean age = 5.2 years, SD 0.5; Early-grafted group), 30 children (18 boys and 12 girls; mean age = 5.8 years, SD 0.8; Non-grafted group), and 40 children (25 boys and 15 girls, mean age = 5.8, SD 0.4; non-cleft Control group). Children from Early-grafted and Non-grafted groups had a CUCLP repaired with a one-stage closure of the entire cleft. An alveolar bone grafting was performed in the Early-grafted group between 2 and 4 years (mean = 2.4, SD 0.6). A one-way anova model with post hoc Tukey's multiple comparison procedures were used to identify intergroup differences. RESULTS: The mesiopalatal inclination of the lesser segment in the Early-grafted group was decreased in comparison with the Non-grafted and Control groups. The intercanine width had a tendency to be reduced in the Early-grafted group relative to Non-grafted group. CONCLUSIONS: Early bone grafting results in a larger collapse of the lesser segment than bone grafting carried out between 9 and 12 years of age.

Choline and halogen derivatives of CMA (9-oxo-10-acridine acetic acids) as tools for monitoring the interaction of the interferon inducers via a specific receptor.

New choline and halogen derivatives of CMA (9-oxo-10-acridine acetic acid) were investigated as interferon (IFN) inducers in mice and in the mouse bone marrow-derived macrophage cultures. Two of the choline derivatives, DMCMA and CSCMA, were active IFN inducers presumably because they were hydrolyzed so as to release CMA. The halogen analogues of CMA were inactive or weak IFN inducers in vivo and in vitro. On the contrary, the Br and I derivatives of CMA were potent inhibitors of IFN induction by CMA in vitro. The behavior of the agonists and antagonists of CMA suggests that the induction of interferon may occur indirectly via a specific CMA-receptor complex.

Effects of interferons, interferon inducers and growth factors on phagocytosis measured by quantitative determination of synthetic compound ingested by mouse bone marrow-derived macrophages.

Sodium salt of 9-oxo-10-acridineacetohydroxamic acid (HCA), a new synthetic compound, forms small crystals in aqueous solution. These crystals were easily phagocytized by the mouse bone marrow-derived macrophages. The ingested HCA crystals were visible under light microscope as dark granules. The degree of phagocytosis was estimated by the spectroscopic measurements of absorption of ingested HCA. About 10 day-old cultures of mouse bone marrow-derived macrophages were found to be suitable for a study on the effect of murine or human interferons. It was observed that murine interferons alpha, beta and gamma at low concentrations (10-200 U/ml) stimulated and higher concentrations (400-1000 U/ml) had no effect on the phagocytosis. Previous treatment of interferons with anti-IFN sera abolished the effect of the interferons. CMA-induced interferon and growth factors were found to modify the phagocytic activity of macrophage cultures.

Interferon and humoral immune response in experimental influenza. I. Infection with virus unadapted to the mouse.

Production of interferon by the peritoneal and alveolar cells as well as the production of antibody-producing cells by spleen in the experimental influenza in the mouse has been studied. At the time when the replication of virus lung was at the peak the alveolar cells, but not peritoneal cells were found to produce in vitro more interferon than the cells from the uninfected mice. At the same time in the spleen increased number of antibody forming cells (PFC) against sheep red blood cells was observed. In contrast, after intravenous or intraperitoneal injection of 5 X 10(8) EID50 of influenza virus which induced approximately 10(3) units of interferon per ml there was an inhibition of PFC in the spleen.

Effect on influenza virus infection on the production of interferon by alveolar and peritoneal cells in vitro.

The investigation was carried on mice infected with influenza A/053/74/H3N2 virus. 129/Ao/Boy, inbred mice, were inoculated intranasally with influenza virus. The alveolar and peritoneal cells from infected and uninfected animals were induced in vitro with Newcastle disease virus. It was shown that the alveolar cells from infected mice produce more interferon than the cells from control mice, but the peritoneal cells from both groups of animals produced the same amount of interferon.

A simple colorimetric method for the measurement of phagocytosis of crystals of low molecular weight compound by macrophages.

Sodium salt of 9-oxo-10-acridineacetohydroxamic acid (HCA), a new synthetic compound, forms small crystals in aqueous solutions. These crystals were easily phagocytable by the mouse bone marrow-derived macrophages. The ingested HCA crystals were visible under light microscope as dark granules. The counting of cells with the granules allowed the calculation of number of the phagocytic cells in the preparation. It was also possible to measure the amount of ingested HCA by the cells using colorimetric method. The kinetics of phagocytosis of HCA showed that the process was rapid. Quantitative measurements of ingestion of HCA reflected the phagocytic activity of the cultured cells.

Influence of interferon induction with influenza a virus upon the modification of anti-SRBC humoral response.

The investigations carried out showed the dependence of immunosuppression induced by A/USRR/053/74(H3N2) virus upon the activity of its neuraminidase. High activity of this enzyme influenced interferon (IFN) induction which, in turn, reduced the primary humoral response to sheep red blood cells (SRBC) or stimulated the production of IgM and IgG antibody producing cells.

Alterations in leukocytes induced by virus and interferon.

Alterations occurring in cells under an influence of interferon or viral interferon inducer were observed under the fluorescence microscope. The experiments were carried out with human leukocytes stained intravitally with acridine orange. From our observations it follows that both interferon as well as interferon inducer evoke morphological changes in leukocytes causing partial or complete disappearance of lysosomes in cytoplasm.

Tolerance or hyperreactivity to interferon induction by sodium salt of 9-oxo-10-acridineacetic acid and analogs in mice and in the mouse macrophage cultures.

Choline and halogen analogs of 9-oxo-10-acridineacetic acid (CMA) were studied as IFN inducers in mice and in the mouse bone marrow-derived macrophage cultures. Two of the choline analogs--DMCMA and CSCMA were inducers of IFN in the macrophages. The response was found to be dose related. CMA as well as the active analogs were found to induce the hyporeactive state to IFN induction both in mice and in the mouse macrophage cultures. On the other hand, the inhibitor of IFN induction by CMA--the dibromo analog (DBCMA) was found to induce in mice a hyperreactive state to IFN induction by CMA.

Competition of sodium salt of 9-oxo-10-acridineacetic acid with analogs during induction of interferon in the mouse bone marrow-derived macrophages.

Analogs of 9-oxo-10-acridineacetic acid (CMA) including new synthetic compounds, were found to be valuable tools for investigating the mechanism of interferon (IFN) induction. Experiments were performed on the long-term cultures of mouse bone marrow-derived macrophages which are unusually susceptible to IFN induction by CMA. CMA in the optimal nontoxic concentration of 600 micrograms/ml may induce in the macrophages up to 3.500 units of IFN/ml. The response was found to be dose related. The analogs of CMA, compounds 3, 7-16, were found to be inactive as IFN inducers. However, the analogs 3, and 8-16 administered together with the suboptimal doses of CMA enhanced by 10 to 40-fold the interferon response to CMA. On the other hand, the compound 7 was shown to inhibit completely the induction of interferon by CMA. L-tryptophan was inactive as either enhancer or inhibitor of CMA. The mode of action of CMA is explained in terms of the hormonal concept of IFN induction.

Assessment of interferon production in patients with chronic nonviral diseases by whole blood or whole bone marrow techniques.

Hundred and fifty-four samples of heparinized blood from patients with chronic toxoplasmosis, chronic brucellosis, lung diseases, psychiatric affective disorders, healthy individuals and neonates, were obtained. The experimental material included also 14 bone marrow samples from patients with hematological diseases or lung cancer. The whole cell populations were treated with several classical IFN inducers and supernatants were assayed for IFN activity in human lung adenocarcinoma cell line A 549 using VSV or EMC viruses as challenge. The response of WBC to NDV or PHA + PMA was high and remarkably stable in majority of cases except listed below. The levels of IFN induced by LPS were low. The response of WBMC to IFN inducers closely resembled the response of WBC. Low IFN levels in samples of stimulated WBMC from some hematological patients were connected with low cellularity. WBC from psychiatric patients with affective disorders weakly responded to stimulation with NDV. This suggested an existence of deficiency of IFN alpha production connected with affective disorders. Also WBC from cord blood failed to react to PHA + PMA and were poorly responsive to NDV.

N,N-diethylaminoalkoxy-4,7-phenanthrolines and 1,8-diazaflourene derivatives, a novel class of potential interferon inducers and antiviral agents: interactions with nucleic acids in vitro and cellular activities.

Tilorone aza-analogues, derivatives of 4,7-phenanthroline and 1,8-diazafluorene, were examined as DNA-complexing agents by spectral and electrophoretic methods. The binding process includes at least two types of interactions: electrostatic and, possibly, intercalation. Complex formation with the denatured DNA was also observed, but its nature remained unsolved. Binding and thermodynamic parameters were determined. All ligands studied showed weak antiviral activity and essentially no interferon induction when assayed in vitro and in vivo. It was concluded that interferon induction by tilorone may involve specific cell receptors or intermediaries.

Occupational respiratory diseases in laboratory animal workers: initial results.

UNLABELLED: Laboratory-animal allergy (LAA) is a well-known occupational hazard to workers employed in biological or medical research institutes and in the pharmaceutical industry. The aim of this study was to focus on the problem of LAA and to assess factors predisposing to sensitization among subjects occupationally exposed to animals. Sixty workers were examined in our study. They responded to a questionnaire and underwent spirometry (Vital Capacity, VC and Forced Expiratory Volume in one second, FEV1). In addition, Peak Expiratory Flow (PEF) and the histamine provocation test were estimated in 5 subjects that had been hospitalized in the Department of Occupational Diseases. Skin prick tests with common allergens and with hair extracts from laboratory animals were performed, and total IgE levels and specific IgE antibodies were also measured. Among 60 subjects who had been working with animals, 26 had positive skin prick tests for one or more of the common allergens. Five subjects supposed to have occupational bronchial asthma and four with occupational allergic rhinitis showed positive skin prick tests for one or more animal allergens, increased total IgE levels and specific serum IgE antibodies. All these subjects had smoked for years. CONCLUSIONS: 1) Laboratory animal allergy develops within first years of exposure; 2) atopy and smoking predispose to laboratory animal sensitization and to a development of bronchial asthma and allergic rhinitis.

Pharmacokinetics and distribution of selenium in blood and organs of rats.

The dynamics of selenium concentration changes in blood, organs and tissues of rats after a single intragastric administration of selenium yeast and sodium selenite was determined. The course of selenium concentration changes in blood was described, the pharmacokinetic parameters were estimated according to the trivalent equation of dicompartment model and the selenium content in liver, kidneys, small intestine, spleen, heart, brain, stomach, testicles and prostate was determined 48 h after the administration of selenium preparations.

[Poisoning wit organic solvents based on data of the Clinic of the Institute of Occupational Medicine in Lódz 1971-1980]. / Zatrucia rozpuszczalnikami organicznymi w materiale Kliniki Instytutu Medycyny Pracy w Lodzi w latach 1971-1980.

During 1971-1980, 128 patients were hospitalized at the Clinic of Occupational Diseases, Institute of Occupational Medicine, Lódz, for disease resulting from chronic exposure to organic solvents. The authors analyzed diseases syndromes, exposure duration prior to the disease occurrence, and professions and workplaces constituting sources of exposure to solvents. Most significant in occupational health were found to be: benzene and its homologues, chlorinated hydrocarbons and naphtha. However, exposure to solvents occurs not only in industry but also in small service and cottage--work workshops, which fairly hampers preventive measures.

[Laboratory animals as a cause of occupational allergy]. / Zwierzeta laboratoryjne jako przyczyna uczulen zawodowych.

Animal allergens are the strongest occupational allergens which sensitize the respiratory tract. Allergy to the animal is the most important occupational health hazard among people working with experimental animals in university and other research laboratories. The most common manifestations of allergy to laboratory animals are: bronchial asthma, rhinitis, contact urticaria, angioedema and contact dermatitis. The major source of allergen is the excreta and secreta of such animals as: rat, mouse, guinea pig, rabbit, dog, cow and horse. Among risk factors responsible for the development of animal allergy are: atopy, tobacco smoking and allergy to domestic pets. The diagnosis of laboratory animal allergy is usually based on a medical history. The objective evidence to support the diagnosis can be obtained from skin testing, a specific immunologic response and work related changes in peak flow rate. Reduction in the airborne levels of animal allergens not only at home, but also at work (proper ventilation, filter masks, elimination of domestic animals) and reduction of factors responsible for the development of bronchial hyperreactivity (avoidance of smoking), can contribute to decreasing the incidence of diseases.

[Bronchial asthma with inflammation of the nose mucous membrane induced by occupational exposure to methyl methacrylate in a dental technician ]. / Astma oskrzelowa z zapaleniem blony sluzowej nosa w nastepstwie zawodowej ekspozycji na metakrylan metylu u technika dentystycznego.

A case report of a 40-year-old female dental technician with a 13-year history of methyl methacrylate exposure is presented. Symptoms of dyspnea, wheezing, coughing and rhinorrhea occurred 6-8 months after the first occupational contact with methyl-methacrylate containing substances. Skin tests performed with a battery of common allergens produced negative results. While performing a provocation test with methyl-methacrylate, the patient developed severe stridor and dyspnea with concomitant decrease in I second forced expiratory volume (FEV1) and peak respiratory flow (PEF). The increase in leukocytes, eosinophils, basophils, albumin, eosinophil cationic protein (ECP) and mast cell tryptase occurred in nasal lavage fluid after bronchial provocation test. The authors conclude that methyl-methacrylate may cause asthma (probably non-atopic) in persons occupationally exposed to its effect.

Bioavailability of buserelin and gonadorelin in suspensions.

There have been determined parameters defining biological availability of gonadorelin and buserelin marked 125 J. Hormonal preparations were hypodermically administered to the rats in suspensions containing zinc ions of the molar ratio of the hormone: zinc 1:5. It has been stated that buserelin in suspension is better available to an organism than gonadorelin .

The kinetic study of the selenium yeast stability.

The kinetics of degradation of selenium yeast was investigated at different temperatures. The effect of temperature has been determined and from this data, applying of Arrhenius-law, the stability of selenium yeast at 25 degrees C has been predicted and the t10 was determined. The changes in selenium content of the selenium yeast were determined by the fluorimetric method. It was proved, that the decomposition observed the first-order kinetic equations. The shelf life of selenium yeast predicted from the Arrhenius plot exceeded 1126 days. In the other hand the stability of selenium preparation in normal storage conditions (T = 25 degrees C) was determined to compare with predicted values. These results were found in agreement with experimental ones obtained at room temperature. No discernible physical changes of selenium preparations were observed after the storage in normal conditions (25 degrees C).