Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Paromomycin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources
PubMed1996

Stable coexpression of a drug-resistance gene and a heterologous gene in an ancient parasitic protozoan Giardia lamblia.

Manipulation of gene expression in Giardia lamblia, one of the most ancient eukaryotes, may provide insights into the evolutionary transition from prokaryotes to eukaryotes. Two recent successes in transient expression of the firefly luciferase (luc) gene in G. lamblia were mediated by a 5'-untranslated region (UTR) of the Giardia glutamate dehydrogenase (gdh) gene and a giardiavirus (GLV) genomic transcript, respectively. We now report a stable coexpression of luc gene with a neomycin phosphotransferase (neo(r)) gene in G. lamblia. An in vitro transcript of the construct pC670-Neo; containing the neo(r) encoding region flanked with the 5'670 nucleotides (nt) and the 3'2022 nt portion of GLV positive strand RNA, was electroporated into G. lamblia trophozoites that were infected with GLV. G418-resistant Giardia trophozoites were cloned, and the neo(r) mRNA in these clones was found to increase with increasing G418 pressure. This drug resistance remained stable upon continuous in vitro cultivation in the absence of G418 for over 15 days. Another plasmid pNeo/GDH/Luc, was constructed by inserting luc gene downstream from the neo(r) gene and the 193 nt 5' portion of gdh gene in pC670-Neo, and its bicistronic in vitro transcript was introduced into GLV-infected G. lamblia by electroporation. The transfectants demonstrated G418-resistance and persistent luciferase activity at levels parallel to the amount of G418 used for selection, peaking at a level of several thousand-fold above the background. Taken together, these data indicate that the neo(r) gene provides an effective selection marker for transformation of Giardia trophozoites, and the bicistronic RNA transfection vector may open the way for functional analysis of other genes in Giardia.

Amebicides↗
PubMedDate not supplied

Total deafness from aminoglycoside overdosage: histopathologic case study.

A 57-year-old patient became totally deaf two days after receiving excessive doses of the aminoglycosidic antibiotic lividomycin parenterally for 14 days; she died four and a half months later. Her temporal bones were examined by microdissection, surface preparation, and serial sectioning of the modiolus. Loss of inner and outer cochlear hair cells was virtually complete. Refractile concretions were scattered along the atrophic stria vascularis, especially in the middle turn. The distal half of the radial cochlear nerve fibers in the osseous spiral lamina had degenerated, but closer to the modiolus they appeared to be intact. The spiral ganglion in the basal turn showed partial loss of neurons. Scanning electron microscopy revealed hair cell loss from the vestibular end-organs, more severe in the ampullar cristae than in the utricular macula. The dark cells of the utricular wall appeared to be altered.

Chemical Phenomena↗
PubMed1977

Stability of 70S ribosomes in relation to misreading and antibacterial activity of aminoglycosides.

The anomeric aminoglycosides, RU 21886 and RU 23468, which both have a 2-deoxystreptamine residue, stabilize 70S ribosomes to similar extents at low magnesium ion concentrations. Only RU 21886, however, has marked antibacterial and bactericidal activity and gives rise to a high level of misreading in cell-free protein synthesizing systems. It would thus appear that the ability to stabilize the association of the two ribosomal subunits does not necessarily lead to errors in translation.

Aminoglycosides↗
PubMed1998

The pharmacology of leishmaniasis.

The development of new strategies on chemotherapy of parasitic protozoan diseases is one of the most exciting research fields of recent years. World Health Organization (WHO) reports have recognized that the physiology and biochemistry of protozoan parasites and the host-parasite relation are the main targets for the design of new drugs that can be used in the future against these diseases.

Allopurinol↗
PubMed2000

Amoebic abscess.

Explore the source record for details and available documents.

Abdominal Pain↗
PubMed2001

Aminoglycoside binding to human and bacterial A-Site rRNA decoding region constructs.

The 16S bacterial ribosomal A-site decoding rRNA region is thought to be the pharmacological target for the aminoglycoside antibiotics. The clinical utility of aminoglycosides could possibly depend on the preferential binding of these drugs to the prokaryotic A-site versus the corresponding A-site from eukaryotes. However, quantitative aminoglycoside binding experiments reported here on prokaryotic and eukaryotic A-site RNA constructs show that there is little in the way of differential binding affinities of aminoglycosides for the two targets. The largest difference in affinity is 4-fold in the case of neomycin, with the prokaryotic A-site construct exhibiting the higher binding affinity. Mutational studies revealed that decoding region constructs retaining elements of non-Watson-Crick (WC) base pairing, specifically bound aminoglycosides with affinities in the muM range. These studies are consistent with the idea that aminoglycoside antibiotics can specifically bind to RNA molecules as long as the latter have non-A form structural elements allowing access of aminoglycosides to the narrow major groove.

Algorithms↗
PubMed1997

RNA as a drug target.

Historically, the pharmaceutical industry has focused on proteins, rather than nucleic acids, as drug targets. But recent advances in the fields of RNA synthesis, structure determination and therapeutic target identification make the systematic exploitation of RNA as a drug target a realistic goal.

Animals↗
PubMed1998

Specificity of aminoglycoside antibiotics for the A-site of the decoding region of ribosomal RNA.

BACKGROUND: Aminoglycoside antibiotics bind to the A-site of the decoding region of 16S RNA in the bacterial ribosome, an interaction that is probably responsible for their activity. A detailed study of the specificity of aminoglycoside binding to A-site RNA would improve our understanding of their mechanism of antibiotic activity. RESULTS: We have studied the binding specificity of several aminoglycosides with model RNA sequences derived from the 16S ribosomal A-site using surface plasmon resonance. The 4,5-linked (neomycin) class of aminoglycosides showed specificity for wild-type A-site sequences, but the 4,6-linked class (kanamycins and gentamicins), generally showed poor specificity for the same sequences. Methylation of a cytidine in the target RNA, as found in the Escherichia coli ribosome, had negligible effects on aminoglycoside binding. CONCLUSIONS: Although both 4,5- and 4, 6-linked aminoglycosides target the same ribosomal site, they appear to bind and effect antibiotic activity in different manners. The aminoglycosides might recognize different RNA conformations or the interaction might involve different RNA tertiary structures that are not equally sampled in our ribosome-free model. These results imply that models of ribosomal RNA must be carefully designed if the data are expected to accurately reflect biological activity.

Anti-Bacterial Agents↗
PubMed2000

Treatment of visceral leishmaniasis (kala-azar): a decade of progress and future approaches.

In 1990, there was essentially one treatment regimen in use for visceral leishmaniasis (kala-azar) around the world: 20 to 28 days of daily injections of pentavalent antimony (Sb). During the past 10 years, however, new agents have been tested alone or in combination, in more than 50 studies carried out worldwide. This renewed clinical effort was spurred by a variety of factors, including the emergence of large-scale Sb unresponsiveness in India, where up to one-half of the world's cases of kala-azar now are found. As this new decade opens, the success of this clinical research effort is tangible: three additional, highly effective parenteral regimens now are available (amphotericin B, lipid formulations of amphotericin B, aminosidine), and an active oral agent, a long sought after objective in kala-azar, has been identified (miltefosine). This report reviews the evolution of treatment of visceral leishmaniasis, considers the interaction of the immune response and chemotherapy, highlights therapeutic successes and failures, examines advantages and disadvantages of current treatments, and looks at future therapeutic approaches to the management of this disseminated intracellular protozoal infection.

Adult↗
PubMed2000

Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translation system.

The translation machinery recognizes codons that enter the ribosomal A site with remarkable accuracy to ensure that polypeptide synthesis proceeds with a minimum of errors. When a termination codon enters the A site of a eukaryotic ribosome, it is recognized by the release factor eRF1. It has been suggested that the recognition of translation termination signals in these organisms is not limited to a simple trinucleotide codon, but is instead recognized by an extended tetranucleotide termination signal comprised of the stop codon and the first nucleotide that follows. Interestingly, pharmacological agents such as aminoglycoside antibiotics can reduce the efficiency of translation termination by a mechanism that alters this ribosomal proofreading process. This leads to the misincorporation of an amino acid through the pairing of a near-cognate aminoacyl tRNA with the stop codon. To determine whether the sequence context surrounding a stop codon can influence aminoglycoside-mediated suppression of translation termination signals, we developed a series of readthrough constructs that contained different tetranucleotide termination signals, as well as differences in the three bases upstream and downstream of the stop codon. Our results demonstrate that the sequences surrounding a stop codon can play an important role in determining its susceptibility to suppression by aminoglycosides. Furthermore, these distal sequences were found to influence the level of suppression in remarkably distinct ways. These results suggest that the mRNA context influences the suppression of stop codons in response to subtle differences in the conformation of the ribosomal decoding site that result from aminoglycoside binding.

Animals↗
PubMed1995

Neomycin inhibition of the hammerhead ribozyme involves ionic interactions.

To investigate the properties of the neomycin-hammerhead interaction, inhibition of hammerhead activity was measured as a function of magnesium concentration and pH. The data are consistent with a simple competition between magnesium and neomycin with about five magnesium ions required to displace neomycin from the hammerhead. The pH dependence of the inhibition of hammerhead cleavage by neomycin and two related aminoglycosides was also determined. The data indicate that at least three of the five positively charged ammonium ions present on neomycin are critical for inhibiting hammerhead function. Taken together, these results suggest that the neomycin-hammerhead interaction is mostly ionic in character.

Base Sequence↗