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I Jordan

Publications and source records attributed to I Jordan.

18 recordsLinked to original sources
PubMed2000

Ribavirin inhibits West Nile virus replication and cytopathic effect in neural cells.

West Nile virus (WNV) is an emerging mosquito-borne pathogen that was reported for the first time in the Western hemisphere in August 1999, when an encephalitis outbreak in New York City resulted in 62 clinical cases and 7 deaths. WNV, for which no antiviral therapy has been described, was recently recovered from a pool of mosquitoes collected in New York City. In anticipation of the recurrence of WNV during the summer of 2000, an analysis was made of the efficacy of the nucleoside analogue ribavirin, a broad-spectrum antiviral compound with activity against several RNA viruses, for treatment of WNV infection. High doses of ribavirin were found to inhibit WNV replication and cytopathogenicity in human neural cells in vitro.

Antiviral Agents↗
PubMed2000

Expression and characterization of the Borna disease virus polymerase.

Borna disease virus is the prototype of a new family, Bornaviridae, within the order Mononegavirales, that is characterized by nuclear transcription, splicing, low level replication, and neurotropism. The products of five open reading frames predicted from the genomic sequence have been confirmed; however, expression of the sixth, corresponding to the putative viral polymerase (L), has not been demonstrated. Here, we describe expression and characterization of a 190-kDa protein proposed to represent L. Expression of this protein from the third transcription unit of the viral genome is dependent on a splicing event that fuses a small upstream open reading frame in frame with the larger downstream continuous open reading frame. The protein is detected by serum antibodies from infected rats and is present in the nucleus, where it colocalizes with the phosphoprotein. L is also shown to be phosphorylated by cellular kinases and to interact with the viral phosphoprotein in coimmunoprecipitation studies. These findings are consistent with the identity of the 190-kDa protein as the viral polymerase and provide insights and describe reagents that will be useful for Bornavirus molecular biology and pathobiology.

Amino Acid Sequence↗
PubMed1999

Genetic analysis of West Nile New York 1999 encephalitis virus.

Analysis of the genome of the flavivirus responsible for the 1999 New York City encephalitis epidemic cloned from human brain by reverse-transcription polymerase chain reaction Indicates its identity as a lineage I West Nile virus (WNV; WNV-NY1999) closely related to WNVs previously isolated In the Middle East.

Amino Acid Sequence↗
PubMed1999

Inhibition of Borna disease virus replication by ribavirin.

The guanosine analogue ribavirin was tested for antiviral activity in two neural cell lines, human oligodendrocytes and rat glia, against Borna disease virus (BDV) strains V and He/80. Ribavirin treatment resulted in lower levels of virus and viral transcripts within 12 h. Addition of guanosine but not adenosine resulted in a profound reduction of the ribavirin effect. Ribavirin appears to be an effective antiviral agent for treatment of BDV infection in vitro. A likely mechanism for its activity is reduction of the intracellular GTP pool, resulting in inhibition of transcription and capping of BDV mRNAs.

Adenosine↗
PubMed1996

Expression of human foamy virus reverse transcriptase involves a spliced pol mRNA.

In human foamy virus (HFV) the reverse transcriptase is expressed independently of the Gag protein as a 127-kDa Pol precursor molecule. Evaluating the mechanism of Pol expression we identified a spliced mRNA which uses the main 5' splice donor and a splice acceptor site located in the gag gene. The significance of this spliced transcript for HFV Pol expression was studied by constructing a virus with a mutated splice acceptor site. This virus was unable to express detectable Pol proteins after transient transfection. Replication of the mutant was studied by a sensitive assay based on HFV transactivator-stimulated expression of an integrated lacZ gene under control of the HFV long terminal repeat. Whereas in the first 2 weeks after transfection the mutant replicated 3 to 5 order of magnitude less well than wild-type virus, extracellular titers obtained thereafter were similar to those of wild-type virus. This increase in replication competence was accompanied by a reversion of the mutated splice acceptor site. The results underlined the importance of the spliced pol transcript for HFV replication and pointed to a second mechanism of Pol expression. Indicator gene assays suggest that this other mechanism is likely to be a transactivator-dependent cryptic promoter in the gag gene which gives rise to Pol-encoding transcripts.

Animals↗
PubMed1996

Foamy virus reverse transcriptase is expressed independently from the Gag protein.

In the foamy virus (FV) subgroup of retroviruses the pol genes are located in the +1 reading frame relative to the gag genes and possess potential ATG initiation codons in their 5' regions. This genome organization suggests either a + 1 ribosomal frameshift to generate a Gag-Pol fusion protein, similar to all other retroviruses studied so far, or new initiation of Pol translation, as used by pararetroviruses, to express the Pol protein. By using a genetic approach we have ruled out the former possibility and provide evidence for the latter. Two down-mutations (M53 and M54) of the pol ATG codon were found to abolish replication and Pol protein expression of the human FV isolate. The introduction of a new ATG in mutation M55, 3' to the down-mutated ATG of mutation M53, restored replication competence, indicating that the pol ATG functions as a translational initiation codon. Two nonsense mutants (M56 and M57), which functionally separated gag and pol with respect to potential frame-shifting sites, were also replication-competent, providing further genetic evidence that FVs express the Pol protein independently from Gag. Our results show that during a particular step of the replication cycle, FVs differ fundamentally from all other retroviruses.

Amino Acid Sequence↗
PubMed1994

The mammalian transferrin-independent iron transport system may involve a surface ferrireductase activity.

Mammalian cells accumulate iron from ferric citrate or ferric nitrilotriacetate through the activity of a transferrin-independent iron transport system [Sturrock, Alexander, Lamb, Craven and Kaplan (1990) J. Biol. Chem. 265, 3139-3145]. The uptake system might recognize and transport ferric-anion complexes, or cells may reduce ferric iron at the surface and then transport ferrous iron. To distinguish between these possibilities we exposed cells to either [59Fe]ferric citrate or ferric [14C]citrate and determined whether accumulation of iron was accompanied by the obligatory accumulation of citrate. In HeLa cells and human skin fibroblasts the rate of accumulation of iron was three to five times greater than that of citrate. Incubation of fibroblasts with ferric citrate or ferric ammonium citrate resulted in an enhanced accumulation of iron and citrate; the molar ratio of accumulation approaching unity. A similar rate of citrate accumulation, however, was observed when ferric citrate-incubated cells were exposed to [14C]citrate alone. Further studies demonstrated the independence of iron and citrate accumulation: addition of unlabelled citrate to cells decreased the uptake of labelled citrate without affecting the accumulation of 59Fe; iron uptake was decreased by the addition of ferrous chelators whereas the uptake of citrate was unaffected; reduction of ferric iron by ascorbate increased the uptake of iron but had no effect on the uptake of citrate. When HeLa cells were depleted of calcium, iron uptake decreased, but there was little effect on citrate uptake. These results indicate that transport of iron does not require the obligatory transport of citrate and vice versa. The mammalian transferrin-independent iron transport system appears functionally similar to iron transport systems in both the bacterial and plant kingdoms which require the activities of both a surface reductase and a ferrous metal transporter.

Ascorbic Acid↗
PubMed1992

Regulation of iron uptake in Saccharomyces cerevisiae. The ferrireductase and Fe(II) transporter are regulated independently.

Iron is required for the growth of Saccharomyces cerevisiae. High concentrations of iron, however, are toxic, forcing this yeast to tightly regulate its concentration of intracellular free iron. We demonstrate that S. cerevisiae accumulates iron through the combined action of a plasma membrane ferrireductase and an Fe(II) transporter. This transporter is highly selective for Fe(II). Several other transition metals did not inhibit iron uptake when these metals were present at a concentration 100-fold higher than the Km (0.15 microM) for iron transport. Pt(II) inhibited ferrireductase activity but not the ability of cells to transport iron that was chemically reduced to Fe(II). Incubation of cells in a synthetic iron-limited media resulted in the induction of both ferrireductase and Fe(II) transporter activities. In complex media, Fe(II) transport activity was regulated in response to media iron concentration, while the activity of the ferrireductase was not. When stationary phase cells were inoculated into fresh media, ferrireductase activity increased independent of the iron content of the media; in contrast, transporter activity varied inversely with iron levels. These results demonstrate that the ferrireductase and Fe(II) transporter are separately regulated and that iron accumulation may be limited by changes in either activity.

Biological Transport↗
PubMed1991

Regulation of the transferrin-independent iron transport system in cultured cells.

Mammalian cells accumulate iron via the binding of transferrin to high affinity surface receptors, or through a transferrin-independent pathway which involves the uptake of iron-organic anion chelates by a membrane-based transport system. Previously we determined that the transferrin-independent transport system was present on a wide variety of cultured cells (Sturrock, A., Alexander, J., Lamb, J., Craven, C. M., and Kaplan, J. (1990) J. Biol. Chem. 265, 3139-3145). In this communication we demonstrate that the transferrin-independent iron uptake system is regulated differently than the transferrin-mediated pathway. The activity of the transferrin-independent system was unaffected by changes in cellular growth rate, induction of DNA synthesis and cell division, or depletion of cellular iron. Exposure of cells to ferric or ferrous iron, however, resulted in a time-dependent increase in transport activity, due to a change in Vmax with no change in Km. Increased transport activity was seen in a variety of cultured cell types, occurred in the presence of cycloheximide, and persisted for hours after removal of iron. The ability of other transition metals to induce changes in transport, or to compete with iron for accumulation by the transferrin-independent uptake system, was critically dependent on the composition of the media in which the cells were incubated. Metals such as Cu2+ or Zn2+, but not Cd2+ or Mn2+, when dissolved in a balanced salt solution buffered with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, induced changes in the transferrin-independent iron transport system. The same metals which induced changes in transport were ineffective in media containing amino acids, ascorbate, or N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine. The Vmax of the transferrin-independent iron transport system was also elevated by increases in intracellular Ca2+. The effect of iron on transport activity, however, did not result from an iron-induced release of intracellular Ca2+. These results suggest a novel form of regulation in which the presence of extracellular iron induces the appearance of previously cryptic transporters and thus accelerates the clearance of potentially toxic molecules.

Biological Transport↗
PubMed1989

[Quantitative-morphometric characterization of the lung structure in congenital heart defects exemplified by Fallot disease and isolated ventricular septal defect].

The aim of this study was to investigate the possibility of determination of lung changes in congenital deformity of heart and vessels by the method of Weibel and Elias (1967) for count of points in the lung (volume of alveoli and interstitium). The results show that this method is suitable for the estimation of quantitative changes in Morbus Fallot. In order to decide the degree of arteriosclerosis an additional measurement of the wall thickness of lung vessels is necessary in cases of ventricular septal defect. The arteriosclerosis is an important factor for the secondary variations, especially of the right heart. A field of application of this method could be the praeoperative lung biopsy for the clarification of the question of operability.

Adolescent↗
PubMed1984

Heme regulation of HeLa cell transferrin receptor number.

The number of diferic transferrin receptors on HeLa cells decreases when cells are grown in iron-supplemented media. The experiments reported here suggest that heme is the iron-containing compound which serves as the signal for receptor number regulation. When HeLa cells were grown in the presence of hemin, transferrin receptor number decreased to a greater degree than when cells were grown in equivalent amounts of iron supplied as ferric ammonium citrate. Incubation of cells in conditions which increased cellular heme content resulted in a decrease in cellular transferrin receptors. Incubating cells with 5-aminolevulinic acid (thus bypassing the rate-limiting step in heme biosynthesis, 5-aminolevulinic acid synthase) led to a decrease in transferrin receptor number. Incubation of cells with an inhibitor of heme oxygenase, Sn-protoporphyrin IX, also led to a decrease in transferrin receptor number. When cellular heme content was decreased by inhibiting heme synthesis with succinylacetone (an inhibitor of 5-aminolevulinic acid dehydratase), or by depriving cells of iron with deferoxamine, an increase in HeLa cell transferrin receptor number was seen. When HeLa cells were incubated with inducers of heme oxygenase (CoCl2, SnCl2, Co-protoporphyrin IX), transferrin receptor number also increased. The effects of all compounds which alter transferrin receptor number were dependent on the concentration of the supplement, as well as the duration of the supplementation. These experiments suggest that intracellular heme content may be an important signal controlling transferrin receptor number.

Aminolevulinic Acid↗
PubMed1977

[Analysis of therapeutic success and of obstetrical results in sterile marriages].

In the course of sterility therapy 375 pregnancies were observed in 296 patients. 63 women conceived twice or more. At the first visite the mean age of the patients was 25,8 years, the mean duration of sterility 2,7 years. A primary sterility was observed in 207 and a secondary sterility in 98 cases. The main therapeutic procedure was the induction of ovulation with FSH/LH releasing preparations (Clomiphen, Cyclofenil, Epimestrol) (40,3%), followed by the substitution therapy with human gonadotrophins (22,7%). 78 pregnancies ended by spontaneous and 4 by artificially induced abortion. The abortion rate in this study was 20,8 %, exceeding considerably the normal abortion rate. The rate of extrauterine pregnancies was also increased, being 2,4%. There was no significant difference in the abortion rate of pregnancies with or without induction of ovulation. The age at the time of conception and the duration of therapy had no significant influence on the rate of abortions. In 293 pregnancies the duration of gestation exceeded the 28th week. However, 33,1% of these pregnancies had complications that required hospitalisation. Almost 50% of the complications consisted of threatened abortion. The mean duration of gestation was reduced by 5 days, caused by a relatively high frequency of early births (16,9%). The mode of delivery of our patients was in 68,8% spontaneous delivery, in 16,2% caesarian section, in 15,0% forceps or vacuum extractions. This corresponds to the general mode of delivery of our hospital. Only after gonadotrophin therapy a higher caesarian section rate of 26,8% was noted. Out of the 310 live born children, 9,2% had a weight below 2500 g, owing to a multiple pregnancy rate of 4,1%. 4% of the children showed the signs of dystrophia. The perinatal mortality amounted to 5,1%. However, when the gonadotrophin induced multiple pregnancies are excluded, the rate is 2,7%. Only 2 cases of malformations were observed.

Adult↗
PubMedDate not supplied

Borna disease virus.

Borna disease virus (BDV) is unique amongst animal RNA viruses in its molecular biology and capacity to cause persistent, noncytolytic CNS-infection in a wide variety of host species. Unlike other non-segmented negative-strand RNA animal viruses, BDV replicates in the nucleus of the host cell where splicing is employed for expression of a very compact genome. Epidemiological studies indicate a broad host range and geographical distribution, and some investigators have proposed that human infection may result in neuropsychiatric disorders. Experimental Borna disease in neonatal and adult rats provides an intriguing model for immune-mediated disturbances of brain development and function.

Animals↗
PubMedDate not supplied

[Neuromuscular pathology in a critical pediatric patient].

OBJECTIVE: To describe and provide diagnosis guidelines for the neuromuscular pathology of the pediatric critical patients, manifested as extubation difficulty, based in our experience. CLINICAL CASES: A retrospective study has been performed on three patients in the Pediatric Intensive Care Unit that were diagnosed by using clinical, analytical and electromyographical findings. In the three patients the presence of the disorder was suspected due to the extubation difficulty and the hypotony. All them received vecuronium as neuromuscular blockage while dexamethasone was provided to one of them due to a nodal tachycardia. Myopathic causes were discarded in view of the normally of the muscular enzymes. The electromyography showed an axonal disorder in all three child. Neither lumbar puncture nor muscular biopsy were performed in any of them. CONCLUSIONS: The three patients were diagnosed for a drug neuropathy (neuromuscular blocked and/or corticotheraphy). There were described another causes of the critical patient polyneuropathy in the literature, but we didn't find any of them.

Adolescent↗