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Biomedical subjects

G J Gleich

Publications and source records attributed to G J Gleich.

At least 487 records · Page 27Linked to original sources
PubMedDate not supplied

Rapid HPLC screening method for contaminants found in implicated L-tryptophan associated with eosinophilia myalgia syndrome and adulterated rapeseed oil associated with toxic oil syndrome.

In 1981 a massive food-borne epidemic, termed the toxic oil syndrome (TOS), occurred in Spain. Eight years later a closely related disease, the eosinophilia myalgia syndrome (EMS), was reported in the USA with many additional cases being reported worldwide. Although EMS was linked to the ingestion of contaminated L-tryptophan and TOS to aniline denatured rapeseed oil, the etiological agent(s) responsible for both diseases remains unknown. However, contaminants in both the oil and the dietary supplement are believed to have triggered these diseases, and there has been much speculation that a common contaminant may have caused both epidemics. In this report, methods for the facile preparation and HPLC analysis of EMS-implicated L-tryptophan and adulterated rapeseed oil samples associated with TOS are described which allow a direct comparison between the contaminants of both foodstuffs. A combination of solvent and solid phase extraction methods are demonstrated along with the application of C18 reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with on-line UV and MS detection. These methods have allowed us to determine for the first time, based upon this work, that there are no detectable common contaminants that possess a UV response, between EMS implicated L-tryptophan and TOS implicated rapeseed oil samples.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Demonstration of immunoreactive eosinophil granule major basic protein in the plasma and placentae of non-human primates.

A protein immunologically identical to the major basic protein (MBP) of eosinophil granules is present in the plasma of pregnant women and has been localized to human placental X cells using immunofluorescence. This study demonstrates the presence of similar immunoreactive molecules in the placental X cells from several non-human primates. We also describe the presence of increased plasma levels of MBP in the pregnant gorilla and in pregnant cynomolgus and rhesus monkeys as compared to non-pregnant counterparts. Such findings suggest that non-human primates are a suitable animal model for the study of the X cell function and in particular the physiological importance of MBP in pregnancy.

Animals↗
PubMedDate not supplied

Plasma levels of eosinophil granule major basic protein in pregnant cynomolgus monkeys.

The sera of all pregnant women contain increased amounts of a protein biochemically and immunologically similar to the eosinophil granule major basic protein (MBP). Immunofluorescence shows that the pregnancy-associated MBP is localized to placental trophoblastic cells. This information raises important questions about the function of pregnancy-associated MBP because of the potential biological functions attributed to its eosinophil counterpart (namely, its potent toxic and cytostimulatory activities). Previous studies demonstrated the presence of an immunologically cross-reactive protein in the placentae and plasma of pregnant non-human primates. Here, plasma MBP levels were measured throughout gestation in cynomolgus monkeys. In early pregnancy, only modest increases in MBP were found in contrast to the sharp rise observed in the first 20 weeks of human pregnancy. During the final one-third of gestation, striking increases in plasma MBP occurred in the monkeys. This parallels the late rise in MBP seen in humans in the third trimester. Thus, the cynomolgus monkey may serve as a model to clarify the role of the MBP in the biochemical events that culminate in parturition.

Animals↗
PubMedDate not supplied

Analysis of pregnancy-associated major basic protein levels throughout gestation.

Previous studies have shown that MBP levels rise before labour and have suggested the use of pMBP levels as a predictor of labour. We hypothesize that pMBP levels show a common pattern in pregnant women including a late third trimester rise in pMBP which predicts the onset of labour. Serum pMBP levels were measured throughout gestation in 112 pregnant women. We then analysed the relationship of pMBP levels to the time of labour onset, and to other features of pregnancy. An exponential increase in pMBP levels was seen early in gestation from weeks 5 to 21 in all pregnant women. In total, 79 per cent of the women showed rises in pMBP of > or = 25 per cent above baseline during the third trimester. pMBP levels were shown to be associated with placental weight, multiple gestation, and parity. pMBP levels could not, however, be used to form a precise model for the prediction of labour. The role of pMBP in pregnancy remains unclear.

Blood Proteins↗
PubMedDate not supplied

The effect of fluticasone propionate aqueous nasal spray on eosinophils and cytokines in nasal secretions of patients with ragweed allergic rhinitis.

Cytokines active on eosinophils are important in the pathogenesis of allergic diseases. A study was conducted to determine if nasal eosinophilia in allergic rhinitis is associated with an increase in eosinophil-active cytokines in nasal secretions and to compare the effects of fluticasone propionate aqueous nasal spray with astemizole and placebo on the levels of these cytokines. Forty-five patients with moderately severe ragweed allergic rhinitis were randomly assigned to receive 2 weeks of treatment with fluticasone propionate aqueous nasal spray 200 micrograms once daily, astemizole 10 mg once daily, or placebo. Nasal lavage was performed in July (preseason), August (peak season), September (after 2 weeks of treatment), and October (postseason). The number of eosinophils, the amount of eosinophil-derived neurotoxin (EDN), and the amount of eosinophil survival-enhancing activity were measured. Total mean nasal symptom scores, concentrations of nasal eosinophils and EDN, and eosinophil survival-enhancing cytokine activity in nasal secretions were significantly lower after 2 weeks of treatment with fluticasone propionate compared with astemizole or placebo. Survival-enhancing activity was detected in the nasal secretions of 25 patients. By blocking activity with monoclonal antibodies, specific cytokines were identified (granulocyte macrophage-colony stimulating factor, 3 samples; interleukin-3, 2 samples; interleukin-5, 5 samples). In conclusion, eosinophil-active cytokine concentrations parallel the nasal symptoms of patients with ragweed allergic rhinitis. Unlike astemizole, fluticasone propionate significantly lowers cytokine activity in nasal tissue, which may contribute to the therapeutic efficacy of the drug.

Adult↗
PubMedDate not supplied

Biotransformation of 3-(phenylamino)-1,2-propanediol to 3-(phenylamino)alanine: a chemical link between toxic oil syndrome and eosinophilia-myalgia syndrome.

During late 1989, the eosinophilia-myalgia syndrome (EMS) developed as an epidemic in the United States, with numerous additional cases reported in several other countries worldwide. Eight years earlier, a closely-related disease, the toxic oil syndrome (TOS), occurred in Spain as a massive food-borne epidemic. Although EMS was linked to the ingestion of tainted L-tryptophan, and TOS to aniline-denatured rapeseed oil, the etiologic agent(s) responsible for both diseases remains undetermined. Contaminants in these foodstuffs are believed to have triggered the diseases. Aniline contaminants, including 3-(phenylamino)-1,2-propanediol (PAP), have been reported in oil used by patients who developed TOS. A related aniline derivative, 3-(phenylamino)-L-alanine (PAA), was recently isolated from L-tryptophan associated with the onset of EMS. Here, we demonstrate the biotransformation of PAP into PAA by both rat hepatocytes and human liver tissue. The structural characterization of PAA was unequivocally determined using on-line HPLC coupled with atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS/MS). This finding is the first reported chemical link between TOS and EMS and suggests that these two related diseases share a common etiology, namely, PAA.

Alanine↗
PubMedDate not supplied

Cytotoxic properties of eosinophil granule major basic protein for tumor cells.

BACKGROUND: Eosinophil granule major basic protein (MBP) mediates many eosinophil-associated immune functions and it adheres eosinophils to parasite targets. METHODS: We compared the toxicities of MBP and melittin to K562 and HL-60 cells using five cytotoxicity methods. RESULTS: Trypan blue staining, propidium iodide/ CellTrackertrade markGreen staining and incorporation of 14C-leucine assays indicated that MBP damages most cells by 1 h. In contrast, 51Cr and lactic dehydrogenase (LDH) release assays indicated that MBP damages most cells only at 20 h. All five methods indicated that melittin damages nearly all cells by 1 h. To resolve these discrepancies, the procedures were modified. Without cell transfer, dye staining methods showed that MBP produces very little cytotoxicity at 4 h. 51Cr and LDH assays, modified to mimic cell transfer, showed increased cytotoxicities at 4 h. The 14C-leucine assay modified by solubilization of cells with SDS and by trichloroacetic acid precipitation showed increased recovery of labeled protein and, thus, lower cytotoxicity, about 50%, at 4 h. CONCLUSION: Overall, MBP's ability to cause molecular and cellular adhesion confounds cytotoxicity measurements. A modified 14C-leucine assay overcame MBP's adhesiveness and provided an accurate measure of cytotoxicity.

Blood Proteins↗
PubMedDate not supplied

Eosinophil-associated inflammation in bronchial asthma: a connection to the nervous system.

Evidence exists that eosinophil cationic proteins damage respiratory epithelium in bronchial asthma. Furthermore, the degree of eosinophilia in the blood and the lung is related to bronchial hyperreactivity. The eosinophil might increase airway irritability by increasing vagal responsiveness. Sensitized challenged guinea pigs develop M2 muscarinic receptor cholinergic dysfunction which is abolished by injection of heparin or polyglutamate and both the eosinophil granule major basic protein and the eosinophil peroxidase act as allosteric M2 receptor antagonists. Thus, eosinophil-associated pulmonary inflammation in asthma may enhance vagally mediated bronchoconstriction.

Animals↗