The acyclic nucleoside phosphonate analog 9-(2-phosphonylmethoxyethyl)adenine (PMEA) was recently found to be effective as an inhibitor of visna virus replication and cytopathic effect in sheep ...choroid plexus cultures. To study whether PMEA also affects visna virus infection in sheep, two groups of four lambs each were inoculated intracerebrally with 106.3TCID50of visna virus strain KV1772 and treated subcutaneously three times a week with PMEA at 10 and 25 mg/kg, respectively. The treatment was begun on the day of virus inoculation and continued for 6 weeks. A group of four lambs were infected in the same way but were not treated. The lambs were bled weekly or biweekly and the leukocytes were tested for virus. At 7 weeks after infection, the animals were sacrificed, and cerebrospinal fluid (CSF) and samples of tissue from various areas of the brain and from lungs, spleen, and lymph nodes were collected for isolation of virus and for histopathologic examination. The PMEA treatment had a striking effect on visna virus infection, which was similar for both doses of the drug. Thus, the frequency of virus isolations was much lower in PMEA-treated than in untreated lambs. The difference was particularly pronounced in the blood, CSF, and brain tissue. Furthermore, CSF cell counts were much lower and inflammatory lesions in the brain were much less severe in the treated lambs than in the untreated controls. The results indicate that PMEA inhibits the propagation and spread of visna virus in infected lambs and prevents brain lesions, at least during early infection. The drug caused no noticeable side effects during the 6 weeks of treatment.
With the aim to design potential inhibitors of ribonucleotide reductase (RR), 2′-O-allyl-β-D-arabinofuranosyl-uracil (
4), -cytosine (
7) and -adenosine (
10) were prepared and evaluated for their ...cytostatic activity against Molt4/C8, CEM and L1210 cell lines. Although our preliminary data do not allow to assess if RR is the intracellular target, the results point to differences in the (anti)metabolic behavior of these compounds. This study also offers a general synthesis of 2′-O-allyl-β-D-arabinofuranosyl nucleosides for potential applications in the preparation of 2′-O-allyl-β-D-oligoarabino nucleotides.
The title compounds, designed in view of their potential activity as ribonucletotide reductase (RR) inhybitors, were prepared and tested on Molt4/C8, CEM and L1210 cell lines. The results point to differences in the (anti)methabolic behavior of these compounds.
Optically pure acyclic nucleoside analogues with a 3(S),5-dihydroxypentyl or 4(R)-methoxy-3(S),5-dihydroxypentyl side chain were synthesized starting from 2-deoxy-D-ribose. The acyclic nucleosides ...were obtained by alkylation of the bases with the mesylates 16 and 17. Of these series of novel nucleoside analogues only 9-3(S),5-dihydroxypent-1-ylguanine (6d) showed marked antiviral activity. It inhibited the cytopathogenicity of herpes simplex virus type 1 (HSV-1) at a concentration of 0.4-0.6 microgram/mL, which thus points to a greater antiviral activity than recently reported for the mixture of the R and S enantiomers (12.5 micrograms/mL). In contrast with 6d, its 4(R)-methoxy derivative 7d did not show antiviral activity, which implies that the 4'-methoxy group is unable to mimic the 1',4'-oxygen bridge of the normal furanose ring.
This letter reports the results of the measurement of single photon production in the reaction e(+)e(-) --> gamma+ invisible particles at centre-of-mass energies root s = 130 and 136 GeV and an ...integrated luminosity of 5.83 pb(-1), collected with the DELP
2',3'-Dideoxycytidinene (ddeCyd), the 2',3'-unsaturated derivative of 2',3'-dideoxycytidine (ddCyd) is, like ddCyd itself, a potent and selective inhibitor of HTLV-III/LAV in vitro. This conclusion ...is based on the relatively high ratio of effective antiviral dose (0.3 microM) versus cell growth inhibitory concentration (20-35 microM) and the lack of any appreciable inhibitory activity against a series of non-oncogenic RNA and DNA viruses. Both compounds were considerably more inhibitory to human lymphoid cell lines than human nonlymphoid or murine cell lines. They were highly dependent on prior activation by deoxycytidine kinase to exert their anti-HTLV-III/LAV and cytostatic effects. In contrast with ddCyd, ddeCyd lost part of its anti-retrovirus effect upon prolonged incubation (10 days) with the virus-infected cells in culture.
Sarcoidosis is a systemic granulomatous disorder. However, when epithelioid cell granulomata are found in association with malignancy, they could correspond to a sarcoid reaction.
We report the case ...of a young woman with mediastinal lymphadenopathy containing non-caseating granulomata. She also had a mass in the anterior mediastinum which proved, on surgical resection, to be an intrathymic mature teratoma.
An association between a sarcoid-like reaction and testicular germ cell tumours has been described in literature. Our observation of a sarcoid reaction associated with a teratoma could be due to a hypersensitivity reaction to antigen released by the tumour.
As part of the European Union program of European Scientist Sequencing
Arabidopsis (ESSA), the DNA sequence of a 24.053-bp insert of cosmid clone CC17J13 was determined. The cosmid is located on ...chromosome 1 at the
PFL locus (position 30 cM). Analysis of the sequence and comparison to public databases predicts seven genes in this area, thus approximately one gene every 3.3 kb. Three cDNAs corresponding to genes in this region were also sequenced. The homologies and/or possible functions of the (putative) genes are discussed. Proteins encoded by genes in this region include a polyadenylate-binding protein (PAB-3) and a GTP-binding protein (Rab7) as well as a novel protein, possibly involved in double-stranded RNA unwinding and apoptosis. Intriguingly, the gene encoding the PAB-3 protein, which is very specifically expressed, is flanked by putative matrix attachment regions.
Presents a collection of slides covering the following topics: Wearable textile systems: reliability concerns; energy-efficiency concerns. MIMO techniques for off-body communication. Reliability ...versus energy-efficiency. Space-time coding versus beam forming. Integrating energy harvesters on textile antennas. Solar-cell PIFA antenna. Robust wearable antennas for GPS/Galileo positioning. Providing stable performance in adverse conditions. On-body wearable repeater as relay for implants. In-to-out body communication in an endoscopy application. (33 pages)
The in vitro antiviral and antitumor activities of (-)-debromoeudistomin K (1a) and 10 structural analogues (1b-1j and 11) were evaluated. The synthesis was accomplished with an intramolecular ...Pictet-Spengler condensation reaction as the key step. This examination revealed some structural and stereochemical features that are important for both the antiviral and antitumor activities. The most striking points for activity are the necessity to have the correct natural stereochemistry at both C(1) and C(13b) and the presence of the C(1)-NH2 substituent. As was revealed before with naturally isolated eudistomins a substituent in the indole ring greatly influences the biological activity. The 5-OMe derivative 1h shows high potency in both antiviral and antitumor models.
A novel MEMS device architecture: the SOI SG-MOSFET, which combines a solid-state MOS transistor and a suspended metal membrane in a unique metal-over-gate architecture, is proposed. A unified ...physical analytical model (weak, moderate and strong inversions) is developed and used to investigate main electrostatic characteristics in order to provide first-order design criteria for low-voltage operation and high-performance. It is demonstrated that the use of a thin gate oxide (<20 nm) is essential for a high C/sub on//C/sub off/ ratio (>100) and a low spring constant (<100 N/m) is needed for low voltage (<5 V) actuation. An adapted fabrication process is reported.