PubMed Health⌕ Search

Biomedical subjects

L Fransen

Publications and source records attributed to L Fransen.

At least 55 records · Page 3Linked to original sources
PubMed1986

Treatment of murine interferon-alpha/beta-sensitive and -resistant friend leukemia cells with tumor necrosis factor in combination with murine interferon-alpha/beta or -gamma.

Interferon-alpha/beta (IFN-alpha/beta)-sensitive (FLC 745) and -resistant (FLC 3Cl8) Friend leukemia cells (FLC) were fairly refractory to the cytotoxicity of murine tumor necrosis factor (MuTNF) in vitro. Both lines became highly sensitive to mTNF when treated in combination with murine IFN-gamma; when treated with IFN-alpha/beta, only the FLC 745 became sensitive to MuTNF. Romeo et al. have reported previously that an antiviral state was induced in both FLC lines by IFN-gamma, but only in FLC 745 by IFN-alpha/beta. The present results suggest that the sensitivity to the synergistic cytotoxic effect of IFN and TNF in these cells is correlated with the ability to be induced into an antiviral state.

Animals↗
PubMed1986

Ophthalmia neonatorum in Nairobi, Kenya: the roles of Neisseria gonorrhoeae and Chlamydia trachomatis.

Among 149 consecutive infants with ophthalmia neonatorum in Nairobi, Neisseria gonorrhoeae was recovered from 43%, Chlamydia trachomatis from 13%, and both microorganisms from 4%. Three of five isolates of C. trachomatis belonged to trachoma serovars. The sensitivity and specificity of a gram-stained smear for the diagnosis of gonococcal conjunctivitis were 86% and 90%, respectively. Patients with gonococcal conjunctivitis had more purulent discharge, a higher clinical severity score, and a younger age at onset of disease. Corneal epithelial edema with superficial keratitis was present in four (16%) of 25 patients with gonococcal conjunctivitis but in none of 22 other patients (P = .07). N. gonorrhoeae or C. trachomatis was isolated from the pharynx in 11 (15%) and six (23%) cases, respectively. Oropharyngeal gonococcal infection was associated with coughing (P = .007).

Chlamydia trachomatis↗
PubMed1986

Three day oral course of Augmentin to treat chancroid.

Amoxycillin and clavulanic acid (Augmentin; Beecham Research Laboratories) was used to treat patients with bacteriologically proved chancroid in three different dose regimens. A single dose of Augmentin (amoxycillin 3 g, clavulanic acid 350 mg) was found to be ineffective. A similar dose repeated after 24 hours was equally ineffective, but a dose (amoxycillin 500 mg, clavulanic acid 250 mg) given every 8 hours for three days was found to be effective. The drug was well tolerated and no side effects were noted in any of the patients treated.

Administration, Oral↗
PubMed1985

Molecular cloning and expression of human tumor necrosis factor and comparison with mouse tumor necrosis factor.

U-937 cells, a monocytic line derived from a human histiocytic lymphoma, were induced for human tumor necrosis factor (TNF) secretion into the medium and were used for the preparation of TNF mRNA. Biological activity of the latter was quantified in a Xenopus laevis oocyte injection system. TNF mRNA was enriched by gradient centrifugation and this size-fractionated mRNA was used for synthesis of cDNA and inserted into the unique PstI site of pAT153. A recombinant plasmid containing human TNF cDNA was selected by colony hybridization using an internal fragment of a mouse TNF cDNA clone [Fransen, L., Mueller, R., Marmenout, A., Tavernier, J., Van der Heyden, J., Kawashima, E., Chollet, A., Tizard, R., Van Heuverswyn, H., Van Vliet, A., Ruysschaert, M. R. & Fiers, W. (1985) Nucleic Acids Res. 13, 4417-4429] as a probe. The sequence of this human TNF cDNA is in agreement with the one published by Pennica et al. [Pennica, D., Nedwin, G. E., Hayflick, J. S., Seeburg, P. H., Derynck, R., Palladino, M. A., Kohr, W. J., Aggarwal, B. B. & Goeddel, D. V. (1984) Nature (Lond.) 312, 724-729]. The 157-amino-acid-long mature sequence is about 80% homologous to mouse TNF and its hydrophilicity plot is also very similar, in spite of the apparent species specificity of TNF. In contrast to mouse TNF, it contains no potential N-glycosylation site. When compared to other cytokines, like IFN-beta, IFN-gamma, or IL-2, there is a remarkably high preference for G X C pairs in the third-letter positions. Expression of the TNF cDNA in monkey COS cells or in Escherichia coli gives rise to a protein having similar biological and serological properties as natural human TNF. A human genomic clone was also identified and sequenced; it was found to be in good agreement with the one recently published by Shirai et al. [Shirai, T., Yamaguchi, H., Ito, H., Todd, C. W. & Wallace, R. B. (1985) Nature (Lond.) 313, 803-806], except for some differences in the introns and 5'-untranslated region.

Amino Acid Sequence↗
PubMed1985

Molecular cloning of mouse tumour necrosis factor cDNA and its eukaryotic expression.

Tumour necrosis factor (TNF), released by induced macrophages, causes tumour necrosis in animals and kills preferentially transformed cells in vitro. mRNA induced in the established mouse monocytic PU 5.1.8 cell line by lipopolysaccharide, was converted into double-stranded cDNA and cloned in the pAT153 vector. Recombinant plasmids were screened by plus-minus hybridization and TNF-specific oligonucleotide probes constructed on the basis of partial amino acid sequences of rabbit TNF. A series of TNF specific clones were identified and confirmed by hybrid selection of mouse TNF-specific mRNA. The sequence codes for a 235 amino acids long polypeptide, of which 156 amino acids presumably correspond to the mature product. It can be concluded that mature mouse TNF is a glycosylated dimer. Biologically active TNF was secreted by both Cos-I and CHO-cells transfected with the chimaeric expression vector pSV2d2-mTNF containing the coding region of the mouse TNF cDNA gene.

Amino Acid Sequence↗
PubMed1985

Antimicrobial susceptibility testing and phenotyping of Neisseria gonorrhoeae isolated from patients with ophthalmia neonatorum in Nairobi, Kenya.

Antimicrobial susceptibility testing, auxotyping-serotyping, and plasmid analysis were performed on 41 ocular isolates, 7 nasopharyngeal isolates, and 18 cervical isolates of Neisseria gonorrhoeae obtained during a recent treatment trial of gonococcal ophthalmia neonatorum in Nairobi, Kenya. Fourteen distinct serovar-auxotype patterns were observed with IB-1/Pro-strains which accounted for 59% of the isolates. Infection with multiple types of gonococci appeared to occur in 22% of the mothers since 4 of 18 paired maternal cervical and neonatal ocular isolates had mismatched serovar-auxotype patterns. Among 10 treatment failure isolates only 1 had a mismatched serovar-auxotype pattern. Six (15%) of the ocular isolates were penicillinase-producing N. gonorrhoeae (PPNG). Five had the 4.4-megadalton (Md) beta-lactamase plasmid and one had the 3.2-Md beta-lactamase plasmid. The 24.5-Md plasmid was found in 5 of 6 PPNG strains and in 8 of 35 non-PPNG strains (P less than 0.02). For most antimicrobial agents, PPNG and non-PPNG strains showed similar patterns of susceptibility. Ceftriaxone was the most active of the antibiotics tested, with all strains having an MIC less than or equal to 0.06 mg/liter. Among non-PPNG strains, 15 (43%) had a penicillin MIC greater than or equal to 2 mg/liter and were considered intrinsically resistant to penicillin. Overall, non-PPNG intrinsically resistant strains had greater resistance to other antibiotics than did non-intrinsically resistant strains (P less than or equal to 0.006). The Mtr phenotype was found in 53% of these strains.

Drug Resistance, Microbial↗
PubMed1984

Single-dose kanamycin therapy of gonococcal ophthalmia neonatorum.

117 infants with gonococcal ophthalmia neonatorum, including 27 with infections due to penicillinase-producing Neisseria gonorrhoeae, were treated as outpatients with five different regimens of single-dose intramuscular kanamycin (75 mg or 150 mg) with saline eye washes, gentamicin eye ointment, or chloramphenicol eye drops. There were no treatment failures among 68 patients treated with 75 mg or 150 mg kanamycin and gentamicin eye ointment (for 3 days). However, the minimum and maximum cumulative probabilities of cure of single-dose kanamycin with saline eye washes (for 3 days) were only 60% and 89%. 1 patient of 15 treated with 150 mg kanamycin plus chloramphenicol eye drops did not respond to treatment. Postgonococcal conjunctivitis developed in 14 (12%) infants, of whom 13 had positive cultures for Chlamydia trachomatis. Nasopharyngeal infection with N gonorrhoeae was eradicated in 9 of 11 infants colonised.

Administration, Topical↗
PubMed1984

Protein kinase activities in immune complexes of simian virus 40 large T-antigen and transformation-associated cellular p53 protein.

Immune complex kinase assays in the simian virus 40 system were performed by incubation of immunoprecipitates containing tumor antigens with [gamma-32P]ATP, followed by analysis of any phosphoacceptor proteins. These assays yielded mainly the viral large T-antigen and, in particular, the associated cellular p53 as endogenous substrates. The nature of these substrates was confirmed by proteolysis techniques. Under specific conditions, casein could be used as an exogenous substrate as well. The kinase reactions showed preference for ATP and MgCl2 instead of GTP or MnCl2. Both phosphoserine and phosphothreonine, but in no case phosphotyrosine, were detected after an immune complex kinase reaction. Apparently, several in vivo phosphorylation sites were recognized in vitro in both large T-antigen and p53, but the presence of some artifactual sites could not be completely excluded. Although contaminating kinases were detectable in the immune complexes, at least the p53 molecules were phosphorylated in vitro in a more specific way. This followed from several characteristics of the immune complex kinase reactions and especially from the strong inhibition of p53 phosphorylation by two anti-large-T monoclonal antibodies. It was shown that large T-antigen showed associated kinase activity, although none of our results could unambiguously demonstrate an intrinsic kinase activity of this protein. Finally, anti-p53 monoclonal antibodies only slightly affected in vitro phosphorylation reactions, whereas a p53 molecule from a simian virus 40-free, chemically transformed human cell line was not phosphorylated in vitro under any condition tested. Thus, it is highly unlikely that the p53 molecule per se carries intrinsic or even associated kinase activities.

Amino Acids↗
PubMed1983

Changes in gene expression and protein phosphorylation in murine cells, transformed or abortively infected with wild type and mutant simian virus 40.

The mechanism of SV40-induced cellular transformation was investigated by two-dimensional gel analysis of 35S- and 32P-labeled proteins of various cells. These included rat and mouse cells, either transformed or abortively infected by SV40 wild type, small t deletion mutants, and a large T temperature-sensitive mutant. Synthesis, turnover, or (de)phosphorylation of multiple protein spots was found to be reproducibly and quantitatively influenced by the transformed and/or infected status. Several of these alterations were attributable to the biological activity of either large T or small t antigen. Most changes in 35S-labeled proteins corresponded to a decreased intensity of the gel spots in transformed cells, while hyperphosphorylated proteins were more common than hypophosphorylated ones. About half of the polypeptide alterations in 35S-and 32P-labeled SV40-transformed rat cells, including a set of 35S-labeled small t-dependent changes were shared by Rous sarcoma virus-transformed cells. In contrast, small t-dependent (de)phosphorylation was rarely detected. Phosphoamino acid analysis of selected phosphoprotein spots of rat cells and alkaline hydrolysis of whole two-dimensional gels did not reveal any evidence for increased tyrosine-specific phosphorylation after SV40-induced transformation. Abortively infected mouse cells showed many protein alterations, also observed in stably transformed cells. However, the latter cells contained additional changes, also affecting several phosphoproteins and possibly related to the establishment of transformation. These findings are discussed in relation to the biological functions, known or presumed, for SV40 large T and small t antigens during transformation.

Animals↗
PubMed1983

Improved localization of phosphorylation sites in simian virus 40 large T antigen.

The location of phosphorylation sites in the large T antigen of simian virus 40 has been studied both by partial chemical cleavage and by partial proteolysis of various forms of large T. These included the full-size wild-type molecule with an apparent molecular weight of 88,000, deleted molecules coded for by the mutants dl1265 and dl1263, and several shortened derivatives generated by the action of a cellular protease. These molecules differed from each other by variations in the carboxy-terminal end. In contrast, a ubiquitous but minor large T form with a molecular weight of 91,000 was found to be modified in the amino-terminal half of the molecule. In addition to the phosphorylation of threonine at position 701 (K.-H. Scheidtmann et al., J. Virol. 38:59-69, 1981), two other discrete domains of phosphorylation were recognized, one at either side of the molecule. The amino-terminal region was located between positions 81 and 124 and contained both phosphothreonine and phosphoserine residues. The carboxy-terminal region was located between approximate positions 500 and 640 and contained at least one phosphoserine residue but no phosphothreonine. The presence in the phosphorylated domains of large T of known recognition sequences for different types of protein kinases is discussed, together with possible functions of large T associated with these domains.

Antigens, Viral↗
PubMed1983

Metabolic turnover of phosphorylation sites in simian virus 40 large T antigen.

Four (groups of) phosphorylation sites exist in the large T antigen of simian virus 40, and they involve at least two serine and two threonine residues (Van Roy et al. J. Virol. 45:315-331, 1983). All the phosphorylation sites were found to be modified and again dephosphorylated at discrete rates, with phosphoserine residues having the highest turnover rate. The measured half-lives ranged between 3 h (for the carboxy-terminal phosphoserine site) and 5.5 h (for the amino-terminal phosphothreonine site). The influence of four temperature-sensitive A mutations on phosphorylation of large T antigen was also examined. At restrictive temperature, phosphorylation of the carboxy-terminal phosphoserine in mutated large T antigen was found to be particularly impaired. These data emphasize the physiological importance of the latter phosphorylation site.

Antigens, Viral↗
PubMed1981

Phosphorylation patterns of tumour antigens in cells lytically infected or transformed by simian virus 40.

The phosphorylation sites of simian virus 40 (SV40) large tumor (T) antigens have been analyzed by partial proteolysis peptide mapping and phosphoamino acid analysis of the resulting products. At least four sites were found to be phosphorylated. An amino-terminal part of the molecule contained both phosphoserine and phosphothreonine. One phosphothreonine residue was located in the proline-rich carboxy-terminal end of the molecule, either at position 701 or at position 708. The mutant dl 1265, which is defective in adenovirus helper function, lacked this phosphorylation site. In addition, the carboxy-terminal part of the molecule contained phosphoserine at a more central position. T-antigen-associated proteins of SV40-transformed cell (nonviral T; 51,000 to 55,000 daltons) also contained multiple phosphorylation sites involving at least two serine residues in mouse antigens and an additional threonine residue in rat, human, and monkey antigens. The latter residue and at least one phosphoserine residue were located near one terminus of the human NVT molecule. We did not find any evidence for phosphorylation of tyrosine residues in any of the multiple species of either large T or nonviral T molecules. Several forms of large T antigens were extracted from both SV40-transformed and SV40-infected permissive and nonpermissive cells, and their phosphorylation patterns were compared. No evidence was found for a different phosphorylation pattern of T antigen in transformed cells.

Animals↗
PubMedDate not supplied

Cost-effectiveness of improved treatment services for sexually transmitted diseases in preventing HIV-1 infection in Mwanza Region, Tanzania.

BACKGROUND: A community-randomised trial was undertaken to assess the impact, cost, and cost-effectiveness of averting HIV-1 infection through improved management of sexually transmitted diseases (STDs) by primary-health-care workers in Mwanza Region, Tanzania. METHODS: The impact of improved treatment services for STDs on HIV-1 incidence was assessed by comparison of six intervention communities with six matched communities. We followed up a random cohort of 12,537 adults aged 15-54 years for 2 years to record incidence of HIV-1 infection. The total and incremental costs of the intervention were estimated (ingredients approach) and used to calculate the total cost per case treated, the incremental cost per HIV-1 infection averted, and the incremental cost per disability-adjusted life-year (DALY) saved. FINDINGS: During 2 years of follow-up, 11,632 cases of STDs were treated in the intervention health units. The baseline prevalence of HIV-1 infection was 4%. The incidence of HIV-1 infection during the 2 years was 1.16% in the intervention communities and 1.86% in the comparison communities. An estimated 252 HIV-1 infections were averted each year. The total annual cost of the intervention was US$59,060 (1993 prices), equivalent to $0.39 per head of population served. The cost for STD case treated was $10.15, of which the drug cost was $2.11. The incremental annual cost of the intervention was $54,839, equivalent to $217.62 per HIV-1 infection averted and $10.33 per DALY saved (based on Tanzanian life expectancy) or $9.45 per DALY saved (based on the assumptions of the World Development Report). In a sensitivity analysis of factors influencing cost-effectiveness, cost per DALY saved ranged from $2.51 to $47.86. INTERPRETATION: Improved management of STDs in rural health units reduced the incidence of HIV-1 infection in the general population by about 40%. The estimated cost-effectiveness of this intervention ($10 per DALY) compares favourably with that of, for example, childhood immunisation programmes ($12-17 per DALY). Cost-effectiveness should be further improved when the intervention is applied on a larger scale. Resources should be made available for this highly cost-effective HIV control strategy.

Adolescent↗
PubMedDate not supplied

Prostitutes are a major reservoir of sexually transmitted diseases in Nairobi, Kenya.

Prostitutes are a major reservoir of sexually transmitted diseases in many developing nations. In Nairobi we found that 16%, 28%, and 46%, respectively, of upper-, middle-, and lower-social strata prostitutes were infected with Neisseria gonorrhoeae. Genital ulcers and infections with Haemophilus ducreyi were more prevalent among prostitutes of the middle and lower social strata. A group of 97 prostitutes of the lower social strata were followed longitudinally to determine the rate of reinfection with N. gonorrhoeae. The mean time to acquisition of a new infection was 12.0 +/- 9.2 days. These results show that in Nairobi prostitutes are a readily identifiable group of high-frequency transmitters of gonococcal infection. Strategies based on intervention in the prostitute reservoir could prove to be an effective means of control of gonococcal infections in developing nations.

Chancroid↗
PubMedDate not supplied

Parents of infants with ophthalmia neonatorum: a high-risk group for sexually transmitted diseases.

One hundred forty-nine mothers and 74 fathers of infants who presented at the Special Treatment Clinic (Nairobi) with ophthalmia neonatorum were evaluated. Neisseria gonorrhoeae was isolated from 60 (40%) of 149 mothers and Chlamydia trachomatis was isolated from 31 (21%). Twenty-six mothers (17.5%) had clinical evidence of endometritis or pelvic inflammatory disease. Mothers with endometritis and/or pelvic inflammatory disease were more often infected with N. gonorrhoeae (65%) than were mothers without these conditions (24%) (P less than or equal to .001). N. gonorrhoeae was isolated from ten (14%) and C. trachomatis from three (9%) of 32 fathers, and nongonococcal urethritis was diagnosed in an additional 21 fathers (28%). Seven of ten men with gonococcal urethritis and 18 of 21 with nongonococcal urethritis had no symptoms. These data confirm that the presence of ophthalmia neonatorum in a neonate should be considered as a strong indicator of sexually transmitted disease in the parents. Although most infections in fathers were asymptomatic, the mothers were at high risk for complications.

Adult↗
PubMedDate not supplied

Single-dose ceftriaxone therapy of gonococcal ophthalmia neonatorum.

Ceftriaxone (125 mg) given as a single intramuscular dose without topical therapy was evaluated in seven infants with smear-positive gonococcal ophthalmia neonatorum. Neisseria gonorrhoeae was isolated from the eyes of six infants, and four of these isolates were penicillinase-producing N. gonorrhoeae. Two infants had concomitant ocular infection with Chlamydia trachomatis. All seven infants, when seen at follow-up, showed marked clinical improvement. Conjunctivitis resolved completely in four infants. One infant was lost to subsequent follow-up, while two infants had persistent ophthalmia due to C. trachomatis. Follow-up eye cultures for N. gonorrhoeae were all negative.

Ceftriaxone↗