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Biomedical subjects

F Nagy

Publications and source records attributed to F Nagy.

At least 73 records · Page 4Linked to original sources

Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8: a new virus in human pathology.

The discovery of a new human herpesvirus in Kaposi's sarcoma (KS) tissue of patients with AIDS has opened up new vistas in virology and oncology. This herpesvirus was first descriptively named KS-associated herpesvirus (KSHV), but was recently renamed human herpesvirus 8 (HHV8). KSHV/HHV8 DNA has been found in all forms of KS, suggesting that it might be involved in the pathogenesis of KS. In addition, KSHV/HHV8 can be detected in both malignant and benign lymphoproliferative disease. KSHV/HHV8 was also found in patients with angiosarcoma of the face and angiolymphoid hyperplasia with eosinophilia. Although only a limited portion of the virus has been sequenced, KSHV/HHV8 is equipped with genes that could confer oncogenic potential. The virus can now be cultured, providing the possibility for studies of viral replication and the mode of transmission. The recently developed serologic assays for antiviral antibodies suggest that infection with KSHV/HHV8 is not ubiquitous because KSHV/HHV8 seropositivity is limited to a small proportion of the population.

Acquired Immunodeficiency Syndrome↗

Characterization of proteins that interact with the GTP-bound form of the regulatory GTPase Ran in Arabidopsis.

Ran, a small soluble GTP-binding protein, has been shown to be essential for the nuclear translocation of proteins and it is also thought to be involved in regulating cell cycle progression in mammalian and yeast cells. Genes encoding Ran-like proteins have been isolated from different higher plant species. Overexpression of plant Ran cDNAs, similarly to their mammalian/yeast homologues, suppresses the phenotype of the pim46-1 cell cycle mutant in yeast cells. The mammalian/yeast Ran proteins have been shown to interact with a battery of Ran-binding proteins, including the guanidine nucleotide exchange factor RCC1, the GTPase-activating Ran-GAP, nucleoporins and other Ran-binding proteins (RanBPs) specific for Ran-GTP. Here, the characterization of the first Ran-binding proteins from higher plants is reported. The yeast two-hybrid system was used to isolate cDNA clones encoding proteins of approximately 28 kDa (At-RanBP1a, At-RanBP1b) that interact with the GTP-bound forms of the Ran1, Ran2 and Ran3 proteins of Arabidopsis thaliana. The deduced amino acid sequences of the At-RanBP1s display high similarity (60%) to mammalian/yeast RanBP1 proteins and contain the characteristic Ran-binding domains. Furthermore, interaction of the plant Ran and RanBP1 proteins, is shown to require the acidic C-terminal domain (-DEDDDL) of Ran proteins in addition to the presence of an intact Ran-binding domain. In whole cell extracts, the GST-RanBP1a fusion protein binds specifically to GTP-Ran and will not interact with Rab/Ypt-type small GTP-binding proteins. Finally, in good agreement with their proposed biological function, the At-Ran and the At-RanBP genes are expressed coordinately and show the highest level of expression in meristematic tissues.

Amino Acid Sequence↗

The ursodeoxycholic acid-p-aminobenzoic acid deconjugation test, a new tool for the diagnosis of bacterial overgrowth syndrome.

OBJECTIVE: To determine the possible complementary role of the ursodeoxycholic acid-p-aminobenzoic acid (UDCA-PABA) loading test in the diagnosis of intestinal bacterial overgrowth. DESIGN: A prospective clinical study. PATIENTS AND METHODS: The hydrogen breath and UDCA-PABA tests were performed simultaneously in 68 patients with suspected contaminated small bowel syndrome (CSBS), and in 10 healthy control subjects. The hydrogen breath test was performed by oral loading of 25 g of lactose and/or 10 g of lactulose. The UDCA-PABA test was carried out by oral loading of 250 mg of UDCA-PABA conjugate, followed by measurement of the amount of PABA excreted in the urine. The diagnosis of bacterial overgrowth was considered to be established when either the hydrogen breath test or the UDCA-PABA test produced abnormal results. RESULTS: Thirty-five of the 68 patients proved to have CSBS. In 13 of these 35 patients, only the enhanced urinary PABA excretion (11.7 +/- 1.42 mg vs. 3.6 +/- 0.68 mg) indicated bacterial overgrowth, 15 of the 35 patients gave only a positive hydrogen breath test, and in the remaining seven cases the results of both tests were abnormal. In eight CSBS patients, the urinary excretion of PABA was decreased significantly following 10-day tinidazole treatment (5.5 +/- 1.29 mg vs. 13.1 +/- 2.07 mg). CONCLUSION: The UDCA-PABA test is a valuable clinical method for the detection of bacterial overgrowth, especially in cases where hydrogen production alone fails to reveal CSBS. It is also a useful procedure for evaluating the efficacy of antibacterial treatment.

4-Aminobenzoic Acid↗

Brassinosteroids rescue the deficiency of CYP90, a cytochrome P450, controlling cell elongation and de-etiolation in Arabidopsis.

The cpd mutation localized by T-DNA tagging on Arabidopsis chromosome 5-14.3 inhibits cell elongation controlled by the ecdysone-like brassinosteroid hormone brassinolide. The cpd mutant displays de-etiolation and derepression of light-induced genes in the dark, as well as dwarfism, male sterility, and activation of stress-regulated genes in the light. The CPD gene encodes a cytochrome P450 (CYP90) sharing homologous domains with steroid hydroxylases. The phenotype of the cpd mutant is restored to wild type both by feeding with C23-hydroxylated brassinolide precursors and by ectopic overexpression of the CPD cDNA. Brassinosteroids also compensate for different cell elongation defects of Arabidopsis det, cop, fus, and axr2 mutants, indicating that these steroids play an essential role in the regulation of plant development.

Arabidopsis↗

The light-induced reduction of the gravitropic growth-orientation of seedlings of Arabidopsis thaliana (L.) Heynh. is a photomorphogenic response mediated synergistically by the far-red-absorbing forms of phytochromes A and B.

Hypocotyls of dark-grown seedlings of Arabidosis thaliana exhibit a strong negative gravitropism, which is reduced by red and also by long-wavelength, far-red light treatments. Light treatments using phytochrome A (phyA)- and phytochrome B (phyB)-deficient mutants showed that this response is controlled by phyB in a red/far-red reversible way, and by phyA in a non-reversible, very-low-fluence response. Crosses of the previously analyzed phyB-1 allele (in the ecotype Landsberg erecta background) to the ecotype Nossen wild-type (WT) background resulted in a WT-like negative gravitropism in darkness, indicating that the previously described gravitropic randomization observed with phyB-1 in the dark is likely due to a second mutation independent of that in the PHYB gene.

Arabidopsis↗

Anti-granulocyte immunoscintigraphy and [99mTc]hexamethylpropyleneamine-oxime-labeled leukocyte scintigraphy in inflammatory bowel disease.

A prospective study was carried out on 13 patients with ulcerative colitis and 11 with Crohn's disease to compare the value of radioimmunoscintigraphy involving 99mTc-labeled antigranulocyte monoclonal antibody (BW 250/183) with that of hexamethylpropyleneamine-oxime-labeled leukocyte scintigraphy. The extent of the process (various segments of the small bowel; ascending, transverse, and descending colon; and rectosigmoideum) was determined in 115 segments by means of radioimmunoscintigraphy and leukocyte scintigraphy and compared with the results of enteroclysis and colonoscopy in 64 segments. The scintigraphic activity, calculated by summing the segment scores, was compared with clinical and laboratory parameters. During radioimmunoscintigraphy, the 24-hr fecal excretion of the antibody was measured. The two methods revealed a different extent of the process (P<0.01). The segmental sensitivity and specificity were 63% and 96% in radioimmunoscintigraphy, and 87% and 94% in leukocyte scintigraphy. Leukocyte scintigraphy proved to be superior in cases with small intestine involvement, but the methods are of similar value in cases with large bowel involvement. The scintigraphic activity determined by radioimmunoscintigraphy and the fecal excretion of monoclonal antibody correlated with seven parameters, while that determined by leukocyte scintigraphy did so with 12 variables. Both methods are of similar value for the detection of large bowel involvement, but leukocyte scintigraphy was the better method for determination of the involved segments in the small intestine. The scintigraphic activity proved a useful parameter, correlating well with the clinical and laboratory variables.

Adult↗

A plant in vitro system for the nuclear import of proteins.

This paper reports the development of an in vitro system that allows the direct assay of protein import into plant nuclei. In this assay the import of fluorescently labelled karyophilic protein substrates into nuclei isolated from evacuolated tobacco BY-2 suspension cells is monitored. It is demonstrated that import of the fluorescently labelled peptide conjugates is rapid, saturable and nuclear localization signal (NLS)-dependent. Exclusion of high molecular weight (70 kDa) dextran and substrates carrying mutated NLS sequences further underline the specificity of this system. Nuclear translocation of karyophilic import substrates in tobacco, similar to mammalian systems, is inhibited by the non-hydrolysable GTP analogue GTP-gamma-S. In contrast, protein uptake is not blocked by wheat germ agglutinin, N-ethyl-maleinimide and iodoacetic acid. Furthermore, it is shown that nuclear import of proteins is only partially inhibited by low temperature (0-4 degrees C). The in vitro nuclear import assay does not depend on exogenously added ATP or cytosolic factors. However, a block of nuclear import with GTP-gamma-S could be overcome by the addition of cytosolic extract, suggesting the dependence on cytosolic factors or proteins. These data indicate that the characteristics of nuclear protein import in plant and mammalian cells are similar, but may be, at least in some respects, also different from each other.

Biological Transport↗

Modulation of regenerative membrane properties by stimulation of metabotropic glutamate receptors in rat deep dorsal horn neurons.

1. Intracellular recordings were obtained from 111 dorsal horn neurons in lamina V, in an in vitro transverse spinal cord slice preparation of the cervical region from young rats. 2. Of these neurons, 28% showed voltage-dependent plateau potentials, mainly underlain by a tetrodotoxin-resistant dihydropyridine-sensitive Ca2+ current. When depolarized, neurons with plateau properties produced accelerating firing frequency, afterdischarge, and bistability. They also exhibited windup of action potentials when stimulated by repetitive intracellular injections of current. 3. Glutamate being the main excitatory transmitter released by primary afferents, we also considered the effects of specific agonists of metabotropic glutamate receptors and showed that they modulate positively (induce or enhance) plateau properties in the deep dorsal horn neurons.

Action Potentials↗

Human herpesvirus 8 in classic Kaposi sarcoma.

Recent studies suggest the role of a new human herpesvirus (HHV8) in the pathogenesis of different forms of Kaposi sarcoma (KS). In the present work we investigated the presence of HHV8 sequences in KS tumour tissues from patient with classic KS. Since clear evidences point to the role of immune suppression in the development of AIDS-associated KS or patients receiving immunosuppressive therapy, immunological investigations were also performed. We could show a highly consequent association of HHV8 sequences with classic KS in the large series of patients supporting our previous findings that this virus might be in some way involved in the pathogenesis of this tumour. In addition immunological examination of the patients revealed a mild decrease in the CD4 positive cell number, a significantly reduced CD4/CD8 ratio, a diminished PHA reactivity and leukocyte migration factor production of lymphocytes. The changes observed in the present study are similar, but much less pronounced than those may be observed in HIV infection.

Aged↗

Cholera toxin elevates pathogen resistance and induces pathogenesis-related gene expression in tobacco.

In animals, plants and fungi, cholera toxin (CTX) can activate signalling pathways dependent on heterotrimeric GTP binding proteins (G-proteins). We transformed tobacco plants with a chimeric gene encoding the A1 subunit of CTX regulated by a light-inducible wheat Cab-1 promoter. Tissues of transgenic plants expressing CTX showed greatly reduced susceptibility to the bacterial pathogen Pseudomonas tabaci, accumulated high levels of salicylic acid (SA) and constitutively expressed pathogenesis-related (PR) protein genes encoding PR-1 and the class II isoforms of PR-2 and PR-3. In contrast, the class I isoforms of PR-2 and PR-3 known to be induced in tobacco by stress, by ethylene treatment and as part of the hypersensitive response to infection, were not induced and displayed normal regulation. In good agreement with these results, microinjection experiments demonstrated that CTX or GTP-gamma-S induced the expression of a PR1-GUS reporter gene but not that of a GLB-GUS reporter gene containing the promoter region of a gene encoding the class I isoform of PR-2. Microinjection and grafting experiments strongly suggest that CTX-sensitive G-proteins are important in inducing the expression of a subset of PR genes and that these G-proteins act locally rather than systemically upstream of SA induction.

Cholera Toxin↗

Expression of tobacco genes for light-harvesting chlorophyll a/b binding proteins of photosystem II is controlled by two circadian oscillators in a developmentally regulated fashion.

Light-induced expression of genes encoding the light-harvesting chlorophyll a/b binding proteins of photosystem II (Cab) was shown to be controlled by a circadian oscillator coupled to the red-light-absorbing plant photoreceptor phytochrome. Here we show that a red-light-insensitive oscillator is also involved in regulating the expression of the Cab genes. We provide evidence that germination leads, in a light-independent manner, to the setting and/or synchronization of endogenous oscillators and that it induces the expression of Cab genes in a circadian fashion. This circadian oscillator is not coupled to phytochrome, as it cannot be reset by red light for at least 44 h after sowing. Short red light pulses given between 12 and 44 h after sowing, however, induce new rhythms without perturbing the already free-running red-light-independent circadian oscillation. At this stage of development, the phytochrome-coupled and uncoupled circadian rhythms coexist. Both circadian rhythms are expressed and exhibit period lengths close to 24 h but are phased differently. At later stages of development (60 h or later after sowing), red light treatments synchronized these free-running rhythms and led to the appearance of a single new circadian oscillation. These data indicate that during early development the expression of single tobacco Cab genes, particularly expression of the Cab21 and Cab40 genes, is controlled in a developmentally dependent manner by two circadian oscillators.

Base Sequence↗

Transcription of tobacco phytochrome-A genes initiates at multiple start sites and requires multiple cis-acting regulatory elements.

Promoter regions of the Nicotiana tabacum PHYA1 and PHYA2 genes display 89% sequence identity. Analysis of the 5' ends of both the PHYA1 and the PHYA2 transcript revealed multiple, distinct mRNA species, each differing in length and in abundance. The levels of the major PHYA1, PHYA2 transcripts were found to be auto-regulated by phytochrome. This auto-regulation was most efficient in 2-8-day old seedlings. Furthermore, we examined the expression pattern of the PHYA1-GUS reporter gene, containing a 4700 bp PHYA1 promoter fragment or its 5'-deletion derivatives, by GUS histochemistry and by RNase protection assays in transgenic tobacco plants. Our data indicate that the PHYA1 promoter contains three regions which are necessary for the maximum level and regulated expression. We show that a 264 bp promoter fragment contains a cis-regulatory element(s) responsible for expression in the root tips of transgenic seedlings. The major cis-regulatory elements required for high-level transcription and expression in other organs are located in separate regions of the PHYA1 promoter. These data indicate the contribution of multiple cis-regulatory elements for the maximum and regulated expression of tobacco genes coding for phytochrome A protein.

Base Sequence↗

Molecular characterization and expression of a tobacco histone H1 cDNA.

We have isolated a 1104 bp tobacco cDNA clone (H1c12) which includes an 846 bp open reading frame. This encodes a polypeptide of 282 amino acid residues and represents the largest plant H1 histone identified so far. The structure of the deduced protein shows the classical tripartite organization of the H1-type linker histones. The expression of the tobacco H1 histone gene(s) corresponding to the H1c12 cDNA clone was examined during different developmental stages. We found that, at the level of steady-state mRNA, expression of gene(s) encoding this H1 histone was rapidly induced in germinating seeds. The H1 gene was expressed in all tissues examined. However, its expression was higher in tissues known to contain meristematic cells. Furthermore, in the leaves of mature plants accumulation of the H1 mRNA exhibits a very characteristic oscillation. This latter finding indicates that, at least in fully developed plants, the expression of this type of H1 histone gene(s) is modulated by a diurnal cycle.

Amino Acid Sequence↗