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At least 325 records · Page 18Linked to original sources
PubMed1982

Genetic evidence for vaccinia virus-encoded DNA polymerase: isolation of phosphonoacetate-resistant enzyme from the cytoplasm of cells infected with mutant virus.

Phosphonoacetate (PAA), at concentrations of 200 micrograms/ml or more, prevented growth of vaccinia virus in HeLa and BSC-1 cells. Spontaneous vaccinia virus mutants, selected at high PAA levels, were resistant to the antiviral effects of the drug. The action of PAA was directed toward an early viral function, since the drug was inhibitory only during the first 4 h of the approximately 15-h growth cycle. Conversely, significant reversal of the antiviral effects was obtained only when the drug was removed at or before the fourth hour of infection. Incorporation of [3H]thymidine into cytoplasmic viral DNA was severely inhibited in cells infected with wild-type virus but not in cells infected with mutant virus. Virus-induced DNA polymerase isolated from the cytoplasm of cells infected with wild-type or mutant virus had indistinguishable chromatographic properties on DEAE-cellulose and phosphocellulose columns. However, the wild-type enzyme was inhibited by relatively low concentrations of PAA, whereas 10-fold higher concentrations were needed for equivalent inhibition of the mutant enzyme. Kinetic analysis indicated that PAA inhibition was noncompetitive with deoxyribonucleoside triphosphates; Ki values for wild-type and mutant DNA polymerases were approximately 25 and 300 microM, respectively. Inhibition of wild-type DNA polymerase was immediate and complete even when PAA was added after initiation of DNA synthesis in vitro, suggesting that chain elongation was affected. These results established that the DNA polymerase is a target of the antiviral action of PAA and provided genetic evidence that this enzyme is virus encoded.

Animals↗
PubMed1980

The influence of the sulphonic group on the biodegradability of n-alkylbenzene sulphonates.

1. Model compounds of the type p-n-alkylbenzene sulphonates, p-n-alkylbenzoic acids and phenylcarboxylic acids were tested for biodegradability. Bioassays were performed with unadapted mixed cultures (soil suspensions) using the Organization for Economic Cooperation and Development (OECD) screening test. 2. Degradation was measured by dissolved organic carbon analysis and g.l.c. or h.p.l.c. 3. p-n-Alkylbenzene sulphonates were resistant to microbial attack. The carboxylated compounds with analogous structures, however, with one exception, were easily decomposed. 4. The results indicate that the persistent character of p-n-alkylbenzene sulphonates is mainly due to the sulphonic substituent.

Bacteria↗
PubMed2002

In vivo IL-10 production reactivates chronic pulmonary tuberculosis in C57BL/6 mice.

The production of immunosuppressive cytokines, such as IL-10 and TGF-beta, has been documented in individuals diagnosed with active tuberculosis. In addition, IL-10 production is increased within the lungs of mice that have chronic mycobacterial infection. Therefore, we hypothesized that the down-regulatory properties of IL-10 might contribute to the reactivation of chronic Mycobacterium tuberculosis infection in mice. To determine the influence of IL-10 on the course of infection, transgenic mice producing increased amounts of IL-10 under the control of the IL-2 promotor were infected with M. tuberculosis via the respiratory route. Mice that overexpressed IL-10 showed no increase in susceptibility during the early stages of infection, but during the chronic phase of the infection showed evidence of reactivation tuberculosis with a highly significant increase in bacterial numbers within the lungs. Reactivation was associated with the formation of macrophage-dominated lesions, decreased mRNA production for TNF and IL-12p40, and a decrease in Ag-specific IFN-gamma secretion. These data support the hypothesis that IL-10 plays a pivotal role during the chronic/latent stage of pulmonary tuberculosis, with increased production playing a potentially central role in promoting reactivation tuberculosis.

Animals↗
PubMed1999

Lyme disease: disparity between culture and polymerase chain reaction detection of Borrelia burgdorferi after exposure to ceftriaxone in vitro.

Polymerase chain reaction is often used for detection of Borrelia burgdorferi in biological specimens. It has been suggested that polymerase chain reaction may be used as a surrogate marker of cell viability. To test this premise, B. burgdorferi cultures were treated with the antibiotic, ceftriaxone, and aliquots were cultured for cell viability and tested by polymerase chain reaction. Ceftriaxone treatment abrogated the ability to subculture B. burgdorferi by three days post-treatment. In contrast, positive polymerase chain reaction results were obtained for up to 56 days after antibiotic treatment. These findings indicate that positive polymerase chain reaction results do not provide proof of bacterial cell viability in vitro.

Borrelia burgdorferi Group↗
PubMed2003

Practical experience of microbiological validation of sterilisation.

The addition of the VDmax method provides manufacturers with a choice of three microbiological validation methods to substantiate a 25 kGy sterilisation dose. This article reports on experiences of applying these methods and suggests ways to handle difficult products.

Colony Count, Microbial↗
PubMed1997

The use of essential drugs. Seventh report of the WHO Expert Committee.

This report presents the recommendations of a WHO Expert Committee responsible for updating and revising the Model List of Essential Drugs. The first part provides guidance for countries wishing to establish national programmes for essential drugs, and includes discussion of quality assurance, post-registration drug studies, drug information and educational activities, research and development, and antiviral drugs. In the light of increasing antimicrobial resistance, particular attention is drawn to the use of reserve antimicrobials. The second part presents the ninth revised model list, together with details of changes that have been made, a glossary of terms and an alphabetical list of all the drugs included.

Aged↗
PubMed1998

In vitro activity of voriconazole against selected fungi.

Fifty-nine isolates consisting of 14 genera and 33 species of ascomycetes, basidiomycetes, and zygomycetes were tested against amphotericin B, fluconazole, itraconazole and voriconazole using an in vitro modified macrobroth dilution procedure based upon the NCCLS M27-A standard method for yeasts. The triazoles voriconazole and itraconazole had similar MIC values, except for Acremonium alabamensis, A. strictum, Fusarium oxysporum, F. solani and Wangiella dermatitidis, which had substantially lower voriconazole MIC values. Voriconazole MIC values were lower than those for itraconazole for the 17 species of Trichosporon tested. Fluconazole had high MIC values, often greater than 128 microg ml-1.

Amphotericin B↗
PubMed1972

Altered chlorplast ribosomal proteins associated with erythromycin-resistant mutants in two genetic systems of Chlamydomonas reinhardi.

The phenotype of several erythromycin-resistant mutants of Chlamydomonas reinhardi was further characterized in terms of the electrophoretic properties of their chloroplast ribosomal proteins. In mutant ery-M2d a single protein of the large (52 S) subunit has altered properties, which probably result from a change in its primary sequence. This mutation is inherited in a Meudelian manner. In mutant ery-U1a, which is inherited in a uniparental manner, a different single protein of the 52 S subunit is altered. This change might result from a change in either the primary sequence of the protein or in some form of secondary modification. These results indicate that these two distinct genetic systems must cooperate in the production of chloroplast ribosomes.

Centrifugation, Density Gradient↗
PubMedDate not supplied

Microbial latency.

The means by which pathogens suppress, subvert, or elude host defenses and establish latent infections include microbially induced immunosuppression or antigenic variation, gaining access to sites of the body that are inaccessible to the immune system, and manipulating of the immune response to the advantage of the pathogen. Various risk factors of the host, such as immunosuppression, may be crucial in determining the frequency with which latency is the outcome of primary infection, as well as the likelihood that subsequent reactivation occurs. Mechanisms of reactivation of latent infections may also be triggered by disruption of anatomic or ecologic barriers, or through the cooperative efforts of a second pathogen. Although viruses, due to their unique ability to incorporate their genetic material into host genomes, are best known for their capacity for persistence, examples of latency can be found among all classes of microorganisms. The clinical and epidemiological importance of microbial latency is enormous, because such infections represent potential reservoirs from which dissemination of pathogens to new susceptibles can occur, because they may reactivate to cause acute or chronic progressive disorders in the original host, and because such infections might play a role in the origin of some human cancers. Few areas of basic research hold greater promise of substantially contributing to our understanding of infectious diseases and the eventual relief of human suffering.

Animals↗
PubMed1996

The synthesis and in vitro antibacterial activity of conformationally restricted quinolone antibacterial agents.

Two series of conformationally restricted quinolone antibacterials were synthesized. One series was restricted by formation of a tetrahydrofuran ring between the C-6 position and the C-7 position of the quinolone ring skeleton. The second series achieved conformational rigidity by formation of a tetrahydrofuran ring between the C-7 and the C-8 positions. These compounds were evaluated for their in vitro antibacterial activity. Compounds 19 and 20 were the most active compounds in either series and were about equipotent.

Anti-Infective Agents↗
PubMed1983

Long-term prophylaxis of urinary infections in women: comparative trial of trimethoprim, methenamine hippurate and topical povidone-iodine.

We randomized 64 patients with a history of recurrent urinary tract infections among 3 regimens of long-term (1 year) prophylactic treatment: 20 were given 100 mg. trimethoprim at night, 25 received 1,000 mg. methenamine hippurate every 12 hours and 19 were asked to cleanse the perineum (especially the periurethral area) twice daily with povidone-iodine solution. The progress of patients in terms of urinary symptoms and/or bacteriuria, changes in periurethral flora, side effects, and hematological and biochemical profiles was followed at regular intervals. All treatments were effective in reducing the incidence of symptomatic attacks when compared to the 12 months immediately before therapy and there was little to choose between the individual regimens on this account. However, trimethoprim was tolerated better than were the other 2 treatment regimens. In the group given trimethoprim most of the breakthrough infections (71.4 per cent) that occurred were caused by trimethoprim-resistant organisms (usually Escherichia coli), while in the other 2 groups the incidence of trimethoprim-resistant organisms causing infection was low (2.7 per cent). Treatment with trimethoprim reduced significantly the periurethral colonization of Escherichia coli.

Administration, Topical↗
PubMed2002

The sensitivity to honey of Gram-positive cocci of clinical significance isolated from wounds.

AIMS: To determine the sensitivity to honey of Gram-positive cocci of clinical significance in wounds and demonstrate that inhibition is not exclusively due to osmotic effects. METHODS AND RESULTS: Eighteen strains of methicillin-resistant Staphylococcus aureus and seven strains of vancomycin-sensitive enterococci were isolated from infected wounds and 20 strains of vancomycin-resistant enterococci were isolated from hospital environmental surfaces. Using an agar incorporation technique to determine the minimum inhibitory concentration (MIC), their sensitivity to two natural honeys of median levels of antibacterial activity was established and compared with an artificial honey solution. For all of the strains tested, the MIC values against manuka and pasture honey were below 10% (v/v), but concentrations of artificial honey at least three times higher were required to achieve equivalent inhibition in vitro. Comparison of the MIC values of antibiotic-sensitive strains with their respective antibiotic-resistant strains demonstrated no marked differences in their susceptibilities to honey. CONCLUSIONS: The inhibition of bacteria by honey is not exclusively due to osmolarity. For the Gram-positive cocci tested, antibiotic-sensitive and -resistant strains showed similar sensitivity to honey. SIGNIFICANCE AND IMPACT OF THE STUDY: A possible role for honey in the treatment of wounds colonized by antibiotic-resistant bacteria is indicated.

Drug Resistance, Bacterial↗
PubMed1997

Transmission of human immunodeficiency virus type 1 resistant to nevirapine and zidovudine. Sydney Primary HIV Infection Study Group.

Human immunodeficiency virus type 1 (HIV-1) resistant to the nonnucleoside reverse transcriptase inhibitor nevirapine and to the nucleoside analogue zidovudine was transmitted from a homosexual man to his sex partner. The virus source patient had commenced combination zidovudine and nevirapine therapy 2.5 years prior to his partner's primary HIV infection. He received both therapies for 7 months, then discontinued nevirapine treatment, continuing to receive zidovudine monotherapy for a further 16 months. He had ceased zidovudine therapy 6 months before the time of his partner's seroconversion. Analysis of major and minor isolates obtained from both patients soon after onset of the recipient's primary HIV infection illness confirmed that an HIV-1 variant mutant at codons 70, 98, and 181 of the viral reverse transcriptase was transmitted. This is the first documented case of transmission of HIV-1 resistant to two antiretroviral compounds.

Adolescent↗
PubMed2000

Evidence for independent development of resistance to HIV-1 reverse transcriptase inhibitors in the cerebrospinal fluid.

OBJECTIVES: To delineate and compare the nature and frequency of mutations known to confer resistance to HIV-1 nucleoside reverse transcriptase inhibitors in the cerebrospinal fluid (CSF) and blood compartments. METHODS: Fifty-three paired CSF and plasma specimens had been prospectively collected and stored from 49 HIV-1 infected patients. These were tested using a commercially available line probe assay which allows the simultaneous detection of wild-type and drug selected variants conferring resistance to one or more drugs: zidovudine, didanosine, zalcitabine, and lamivudine. RESULTS: Of the 53 (58%) paired samples, 31 could be amplified by nested PCR. The current assay's limitation for use with CSF is highlighted as 91% of blood samples amplified compared with 60% of CSF samples showing the assays inability to amplify viral loads below 1000 copies/ml. Of the 31 patients 21 (68%) had identical resistance patterns in the CSF and plasma; the other 10 (32%) patients had a resistance profile in the CSF that was different from that in their plasma. Of these, three samples demonstrated amino acid changes associated with high level zidovudine resistance in the CSF but the blood sample remained genotypically sensitive. Nine samples demonstrated resistance in blood but remained wild-type in the CSF. Resistant genotypes were detected in CSF for all nucleosides except didanosine. CONCLUSIONS: Differences in the positions and frequencies of wild-type and drug selected variants in specimens derived from the CSF and blood compartments were detected in a significant number of patients; this argues for the independent development of drug resistance in the CNS in some patients. These findings may have important implications in guiding antiretroviral therapy in HIV-1 infection.

AIDS Dementia Complex↗