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Biomedical subjects

A Emelyanov

Publications and source records attributed to A Emelyanov.

9 recordsLinked to original sources

Treatment of asthma with lipid extract of New Zealand green-lipped mussel: a randomised clinical trial.

Asthma is a chronic inflammatory disease of the airways mediated, at least in part, by leukotrienes and other lipid mediators. Experimental studies have shown that lipid extract of New Zealand green-lipped mussel, Perna canaliculus, is effective in inhibiting 5'-lipoxygenase and cyclo-oxygenase pathways responsible for production of eicosanoids, including leukotrienes and prostaglandins. The aim of this study was to assess its effect on symptoms, peak expiratory flow (PEF) and hydrogen peroxide (H2O2) in expired breath condensate as a marker of airway inflammation in patients with steroid-naïve atopic asthma in a double-blind randomised, placebo-controlled clinical trial. Forty six patients with atopic asthma received two capsules of lipid extract (Lyprinol) or placebo b.i.d for 8 weeks. Each capsule of lipid extract contained 50 mg omega-3 polyunsaturated fatty acids and 100 mg olive oil, whereas placebo capsules contained only 150 mg olive oil. There was a significant decrease in daytime wheeze, the concentration of exhaled H2O2 and an increase in morning PEF in the lipid extract group compared to the placebo group. There were no significant side-effects. The authors conclude that lipid extract of New Zealand green-lipped mussel may have some beneficial effect in patients with atopic asthma.

Adolescent↗

A novel zebrafish bHLH gene, neurogenin3, is expressed in the hypothalamus.

Many basic helix-loop-helix transcriptional factors play important roles in vertebrate neurogenesis. Among them, Neurogenins act as determination factors and initiate the expression of differentiation genes such as neuroD and other neurogenic genes. Here we describe a zebrafish cDNA (neurogenin3 or ngn3) encoding a novel member of the Neurogenin family closest to mouse Ngn3 and human NGN3. Using a zebrafish radiation hybrid panel, ngn3 was mapped to zebrafish linkage group 13 and the region displayed a conserved synteny with the region of human chromosome 10 containing NGN3. As judged by RT-PCR and whole-mount in situ hybridization, ngn3 expression in zebrafish started much later than other neurogenin genes, at only around 24 h post-fertilization (hpf) and with a higher level of expression on the left side of the anterio-ventral diencephalon. Later at 48 hpf, ngn3 expression was detected in a small number of cells in the tuberal hypothalamus. Unlike Ngn3 in the mouse, zebrafish ngn3 mRNAs were not detected in developing pancreas and spinal cord. Genomic Southern blot hybridization suggested that a closely related sequence is present in the zebrafish genome and the hypothetical gene might result from the recent genome duplication in certain teleost lineage and share the function of the common ancestor with the currently characterized ngn3.

Amino Acid Sequence↗

fgfr3 and regionalization of anterior neural tube in zebrafish.

Here we describe the isolation of the zebrafish fgfr3 gene, its structure and chromosomal location. Expression in wild type embryos occurs in the axial mesoderm, the diencephalon, the anterior hindbrain and the anterior spinal cord. In the hindbrain, a differential expression of fgfr3 was detected at several levels of intensity, with the highest expression in the posterior rhombomere 1 that is morphologically distinct from the anterior part, which develops into the cerebellum. Further, analysis of fgfr3 expression in mutants deficient in the formation of the midbrain-hindbrain boundary (MHB), noi(-/-) and ace(-/-), demonstrated that in the absence of Pax2.1 and FGF8 activity, the expression domains of FGFR3 expand into the MHB, tegmentum, cerebellum and optic tectum, which are the affected structures in these mutants.

Amino Acid Sequence↗

Developmental analysis of ceruloplasmin gene and liver formation in zebrafish.

Formation of the liver in zebrafish has been analyzed during normal embryogenesis using ceruloplasmin (Cp) as a specific marker. The asymmetric expression of Cp has been detected in dorsal endoderm at 16 hpf and later in the early hepatic cells in the yolk sac. The liver primordium can be detected after 32 hpf. In oep-/- mutant, which lacks dorsal endoderm, the liver fails to form. In the notochordless flh-/- mutant, the asymmetry of the liver has been lost. Therefore the notochord, dorsal endoderm and endoderm of the yolk sac play a role in liver formation in zebrafish.

Amino Acid Sequence↗

Expression of two novel zebrafish iroquois homologues (ziro1 and ziro5) during early development of axial structures and central nervous system.

Previously, we reported a zebrafish iroquois gene, ziro3, and its expression during early embryogenesis (Mech. Dev. 87 (1999) 165). In the present study, we have isolated two novel zebrafish iroquois genes, ziro1 and ziro5, homologs of mouse Irx1 and mouse Irx5, respectively. The expression of both genes is initiated in dorsal neuroectoderm and mesoderm during gastrulation. Later, their expression appears in the central nervous system (CNS), excluding the telencephalon and most of the diencephalon. ziro1 expression is complementary to that of ziro3 in the notochord and later in the gut. In contrast, ziro5 expression mostly overlaps with that of ziro3. Interestingly, all three iroquois zebrafish genes are expressed in the notochord while only Irx3 is active in the mouse notochord. Their expression in later stages of embryogenesis was also compared.

Amino Acid Sequence↗

Expression pattern of two zebrafish genes, cxcr4a and cxcr4b.

We cloned and mapped two novel zebrafish genes, cxcr4a and cxcr4b, which are closely related to mammalian CXCR4. Expression analysis by reverse transcription-polymerase chain reaction and in situ hybridization demonstrated that these two genes are expressed in most cell lineages known to express Cxcr4 in mammals. These genes are co-expressed in lateral mesoderm and posterior midbrain. The transcripts of cxcr4a were detected in interneurons and endoderm, whereas cxcr4b was specifically expressed in sensory neurons, motoneurons and cerebellum. In the lateral mesoderm, cxcr4b transcripts appeared earlier than those of cxcr4a. Thus, the function of mammalian CXCR4 could be split between the two zebrafish genes. These genes probably derived from the genome duplication event, which occurred during the evolution of teleosts. Similar pairs of Cxcr4 may exist in other species, where genome duplication has occurred.

Amino Acid Sequence↗

Elevated concentrations of exhaled hydrogen peroxide in asthmatic patients.

BACKGROUND: Airway inflammation is important in the development and progression of asthma. Activation of inflammatory cells induces a respiratory burst resulting in the production of reactive oxygen species, such as H(2)O(2). The aim of this study was to measure the concentration of H(2)O(2) in exhaled breath condensate and its correlation with airway obstruction, airway hyperresponsiveness, and concentration of eosinophil cationic protein (ECP) in serum in 70 steroid-naive, atopic patients with unstable asthma (20 men; age range, 18 to 62 years) and 17 normal subjects (7 men; age range, 19 to 34 years). METHODS: Exhaled H(2)O(2) was measured using a colorimetric assay, and the concentration of ECP in serum was measured using radioimmunoassay. Airway hyperresponsiveness was expressed as the provocative concentration of inhaled histamine causing a 20% fall in FEV(1) (PC(20)). RESULTS: In patients with asthma, the mean H(2)O(2) concentration was significantly elevated compared to values in normal subjects: 0.127 +/- 0.083 mol/L vs 0.024 +/- 0.016 mol/L (p < 0.001). There was a significant correlation among H(2)O(2) concentration, FEV(1), PC(20), and ECP in serum. CONCLUSION: We conclude that exhaled H(2)O(2) is significantly elevated in asthmatic patients. This is correlated with disease severity and indirect markers of airway inflammation. Measurement of exhaled H(2)O(2) may be useful to assess airway inflammation and oxidative stress in asthmatic patients.

Adolescent↗

BSAP (Pax5)-importin alpha 1 (Rch1) interaction identifies a nuclear localization sequence.

BSAP (Pax5) is an essential transcription factor for early B cell and central nervous system development. In later B cell development, BSAP has been implicated in the regulation of 3' Ig enhancers and a number of B cell-specific genes. Previous studies have suggested a role for BSAP-interacting proteins in the regulation of the function of BSAP. Using the yeast two-hybrid system, we identified importin alpha1 (Rch1) as a BSAP-interacting protein. Importin alpha proteins have been shown to escort proteins into the nucleus through interaction with a nuclear localization signal (NLS), composed of short stretches of basic amino acids. A predicted NLS in BSAP (NKRKRDE, located at amino acids 195-201 in the central domain) was confirmed to be essential for interaction with importin alpha1 by the yeast two-hybrid assay. Physical interaction between BSAP and importin alpha1 was detected in vitro by a glutathione S-transferase (GST) pulldown assay. The NLS sequence in BSAP conferred nuclear localization to green fluorescent protein (GFP)-BSAP fusion proteins. Although the N-terminal paired (DNA-binding) domain of BSAP also conferred nuclear localization when coupled to green fluorescent protein, this domain did not bind to importin alpha1 in the yeast two-hybrid assay. The NLS sequence in the central domain of BSAP binds to the C-terminal 98-amino acid fragment of importin alpha1.

Animals↗

Reduced intracellular magnesium concentrations in asthmatic patients.

Magnesium is important in the regulation of bronchomotor tone, and low dietary intake of magnesium has been associated with airway hyperresponsiveness in epidemiological studies. The concentration of magnesium in serum, erythrocytes and urine in 49 patients with asthma (29 males, aged 15-65 yrs) and in 25 normal subjects (15 males, aged 17-36 yrs) was studied by atomic absorption. Magnesium concentrations were significantly lower in erythrocytes and urine in both atopic (n = 26) and nonatopic (n = 23) asthmatic patients as compared with the control group, whereas serum concentrations did not differ. The concentration of magnesium in erythrocytes was not related to the degree of airway obstruction as measured by forced expiratory volume in one second (FEV1) but was significantly correlated with airway hyperresponsiveness measured as the provocative concentration causing a 20% fall in FEV1 to inhaled acetylcholine (r = 0.64; p<0.05). In addition, a magnesium tolerance test showed increased retention of magnesium (58.9% of administered dose in asthmatic patients compared with 8.9% in normal subjects, p<0.05). In conclusion, the low cellular concentration of magnesium may be associated with airway hyperresponsiveness in asthmatic patients.

Adolescent↗