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Biomedical subjects

G Englund

Publications and source records attributed to G Englund.

35 records · Page 2Linked to original sources
PubMed1991

Anti-HIV activity of CD4-Pseudomonas exotoxin on infected primary human lymphocytes and monocyte/macrophages.

CD4(178)-PE40 is a recombinant protein consisting of a portion of human CD4 linked to active domains of Pseudomonas aeruginosa exotoxin A. In previous experiments with human T cell lines, the hybrid toxin was found to selectively kill cells infected with human immunodeficiency virus type 1 (HIV-1), and to inhibit HIV-1 spread in mixtures of infected and uninfected cells. CD4(178)-PE40 inhibits HIV-1 spread in cultured primary human lymphocytes. Moreover, the hybrid toxin selectively kills HIV-1 chronically infected monocyte/macrophage cell lines and inhibits HIV-1 spread in primary macrophage cultures. Control experiments indicate that the protective effects of CD4(178)-PE40 against HIV-1 spread are due to selective killing of the infected cells rather than simply to neutralization by the CD4 moiety. Thus, for the major cell types susceptible to HIV infection in vivo, surface envelope glycoprotein is expressed at sufficient levels to enable binding and internalization of CD4(178)-PE40 and consequent selective cell killing.

Bacterial Proteins↗
PubMed1991

Contribution of NF-kappa B and Sp1 binding motifs to the replicative capacity of human immunodeficiency virus type 1: distinct patterns of viral growth are determined by T-cell types.

Starting with a replication-incompetent molecular clone of human immunodeficiency virus type 1, lacking all the NF-kappa B and Sp1 binding sites present in the native long terminal repeat (LTR), proviruses containing reconstructed LTRs with individual or combinations of NF-kappa B and Sp1 elements were generated and evaluated for their capacity to produce virus progeny following transfection-cocultivation. Virus stocks obtained from these experiments exhibited a continuum of replicative capacities in different human T-cell types depending on which element(s) was present in the LTR. For example, in experiments involving proviral clones with LTRs containing one or two NF-kappa B elements (and no Sp1 binding sites), a hierarchy of cellular permissivity to virus replication (peripheral blood lymphocytes = MT4 greater than H9 greater than CEM greater than Jurkat) was observed. Of note was the associated emergence of second-site LTR revertants which involved an alteration of the TATA box. These results suggest that the human immunodeficiency virus type 1 LTR possesses functional redundancy which ensures virus replication in different T-cell types and is capable of changing depending on the particular combination of transcriptional factors present.

Base Sequence↗
PubMed1990

Randomised double-blind study of norfloxacin and cefadroxil in the treatment of acute pyelonephritis.

In a coordinated, double-blind multi-centre trial, adults with symptoms of acute pyelonephritis were randomly assigned to receive a two-week course of oral treatment with either 400 mg norfloxacin twice daily or 1 g cefadroxil twice daily. Of 197 patients enrolled in the study, 140 could be evaluated for drug efficacy and 193 for drug safety. Norfloxacin gave a significantly higher bacteriological cure rate than cefadroxil, both at 3 to 10 days (98% versus 65%; p less than 0.0001; 95% confidence interval (CI) for difference in proportions 21-46%) and up to eight weeks (87% versus 48%; p less than 0.0001; 95% CI 25-54%) after cessation of treatment. The differences between the two regimens were most pronounced in men and in patients with complicating factors such as diabetes mellitus and urinary tract abnormalities. The clinical response during treatment did not differ between the two groups, but symptomatic recurrences at follow-up were more common in the cefadroxil group (28% versus 3%; p less than 0.0001; 95% CI 14-36%). Adverse events were more often reported by patients receiving cefadroxil (39% versus 22%; p = 0.011; 95% CI 4-30%) and consisted mainly of gastrointestinal disturbances and vulvo-vaginitis. In terms of bacteriological and clinical efficacy and safety, a two-week course of norfloxacin was superior to a two-week course of cefadroxil for oral treatment of community-acquired acute pyelonephritis.

Acute Disease↗
PubMed1990

Norfloxacin vs. pivmecillinam in the treatment of uncomplicated lower urinary tract infections in hospitalized elderly patients.

In a single-blind, randomized study of multicentre trial design 343 hospitalized geriatric patients (median age 83 years) suffering from symptomatic urinary tract infections (UTI) were treated with either norfloxacin 200 mg twice daily or pivmecillinam 200 mg 3 times daily orally for 7 days to compare the clinical efficacy and safety of the antibiotics in the elderly. The pathogen was Escherichia coli in 56.7%, other gram-negative rods in 37.2% and gram-positive cocci in 6.1%. Up to 18 days after cessation of treatment the original pathogen was eradicated in 60.5% of the 114 who were assessable for the effect of norfloxacin therapy and in 36.5% of the 96 patients in the pivmecillinam group (p less than 0.001). Adverse drug reactions, mostly gastrointestinal disturbances, were noticed in single cases.

Aged↗
PubMed1989

Cadralazine challenge in patients with previous hydralazine-induced lupus: a 6-month study.

The objective of this study was to investigate the effect of cadralazine in patients who had previously had hydralazine-induced lupus. There were 11 patients included in the study, 10 of whom were treated for 6 months with 15 or 20 mg cadralazine given once daily in combination with beta-blockers and diuretics. All patients had a history of hydralazine-induced lupus and were slow acetylators. None of the patients included in this study showed any current signs or symptoms of drug-induced lupus. No evidence of lupus-like symptoms or of immunologic laboratory abnormalities were found during the study period. Side effects associated with vasodilator therapy were noted in some patients but were transient and mild. We concluded that a cross-reaction between cadralazine and hydralazine does not seem likely to occur and that cadralazine, because of its chemical properties, probably will not give rise to drug-induced lupus.

Acetylation↗
PubMed1989

Short-term self-treatment of travellers' diarrhoea with norfloxacin: a placebo-controlled study.

In a randomized, double blind, placebo-controlled, multicentre trial, 447 travellers to Africa, Asia or Latin America started three days treatment with norfloxacin 400 mg bd or placebo within 24 h after the onset of travellers' diarrhoea. One hundred and four subjects developed diarrhoea and of those 94 (46 in the norfloxacin group and 48 in the placebo group) could be analysed for efficacy. By the last treatment day, 34 patients in the norfloxacin and 18 in the placebo group were cured (P = 0.0001), four and three improved and five and 19, respectively, were failures. Recurrences were seen in three patients on norfloxacin and eight on placebo. The mean time to cure was 3.2 days in the norfloxacin group and 4.4 days in the placebo group (P less than 0.005). The number of loose stools was significantly lower in the norfloxacin group. Nine adverse events were reported; seven in the placebo and two in the norfloxacin group. Pre- and post-travel faecal samples were studied in 19 patients treated with norfloxacin, 21 treated with placebo and 21 untreated subjects without diarrhoea. In treated subjects, increased frequencies of Escherichia coli resistant to ampicillin, co-trimoxazole, doxycycline and chloramphenicol were found in both groups, though more frequently in the placebo one. No subject had norfloxacin resistant Esch. coli pre- and post-travel.

Adolescent↗
PubMed1987

Norfloxacin versus placebo for prophylaxis against travellers' diarrhoea.

In a randomized, double blind study, 127 subjects travelling to countries outside Northern Europe were given norfloxacin 200 mg or placebo bid as prophylaxis against diarrhoea. Fifty-six subjects randomized to norfloxacin and 59 to placebo fulfilled criteria for evaluation of efficacy and of those, respectively six and 20 (P = 0.0006) developed diarrhoea. The mean duration of symptoms in the placebo group was 3.6 days, while all subjects on norfloxacin had symptoms for one day only. In travellers to Mediterranean Europe or the Canary Islands, no significant differences were seen between norfloxacin and placebo. Among subjects going to Africa, Asia or Latin America, 4/32 subjects on norfloxacin and 16/30 on placebo developed diarrhoea (P = 0.0004). Adverse effects were few and mild. Faeces for aerobic cultures was obtained before travelling and three weeks and then three months post-treatment. Treatment with norfloxacin resulted in a significant reduction of samples yielding aerobic Gram-negative rods but did not affect enterococci. In the placebo group, Gram-negative organisms other than Escherichia coli were increased on return to Sweden and the subjects frequently acquired Gram-negative organisms resistant to antibiotics. In none of the groups was there a tendency towards increased norfloxacin resistance. Biotyping of E. coli showed that in both groups the subjects changed their E. coli strains frequently during and after travelling. This trial showed that norfloxacin is a safe and effective prophylactic agent with no adverse effect on bacterial flora, but that its use should be restricted to travellers to non-European countries.

Adult↗
PubMed1986

The nucleotide sequence of the mRNA encoding the fusion protein of measles virus (Edmonston strain): a comparison of fusion proteins from several different paramyxoviruses.

Membrane fusion is the primary cytopathic effect observed in cells infected with measles virus. The viral protein responsible for this process has previously been defined as the fusion (F) protein. Fusion is activated by the proteolytic cleavage of a precursor molecule (F0) to yield two disulfide-linked polypeptides (F1 and F2). In this paper the mRNA for the membrane fusion protein has been cloned and the resulting cDNAs were sequenced. A mRNA composed of 2377 nucleotides was found to contain one open reading frame which could potentially code for a protein of 550 amino acids. This corresponding gene product was identified as the fusion protein through use of antibodies directed against a synthetic peptide which was constructed from the deduced amino acid sequence. A long and rather G-C rich 5' terminus was found on the mRNA and this noncoding region may play some role in regulation of protein synthesis at the translational level. Protein sequence data derived from the cDNA clones revealed a highly conserved F1 amino terminus which is characteristic of most paramyxoviruses. Very little amino acid homology (except for the conservation of the F1 terminus and 9 cysteines) was evident when the sequence was compared to other paramyxovirus fusion proteins. However an overall hydrophobic nature was characteristic of all the F proteins and hydrophobicity plots for the fusion proteins of 4 different paramyxoviruses were very similar. Computer analysis was also employed to analyze the secondary structure of the measles virus F protein. Large stretches of alpha helix were characteristic of the regions which purportedly interact with membranes. The functional domains of the F protein and their similarity to those of the influenza hemagglutinin protein are discussed in this communication. We concluded that the distribution of hydrophobic regions capable of spanning biological membranes determines the fusogenic nature of the F protein.

Amino Acid Sequence↗
PubMed1986

Evaluation of the structural proteins of the hamster neurotropic strain of measles virus with monoclonal antibodies.

The virus-specified proteins produced by cells persistently infected with hamster neurotropic strain (HNT) of measles virus were assessed by a panel of monoclonal antibodies. In comparison to the Edmonston strain a number of differences were detected. The HA protein lacks epitopes identified by certain monoclonal antibodies. Some of the absent epitopes may relate to agglutination, because this biological phenomenon is not produced by HNT virus. Phosphoprotein (P) of the usual size (70 kDa) was not detected. Instead a protein with an approximate MW of 36 kDa which reacted with one monoclonal anti-P was identified. Although matrix protein (M) was not detected, mRNAs for P and M proteins were present. However, these in contrast to the mRNAs from Edmonston strain, did not translate in vitro. These abnormalities may relate to neurotropism and the capacity of HNT to produce persistent CNS infection.

Animals↗
PubMed1986

Matrix genes of measles virus and canine distemper virus: cloning, nucleotide sequences, and deduced amino acid sequences.

The nucleotide sequences encoding the matrix (M) proteins of measles virus (MV) and canine distemper virus (CDV) were determined from cDNA clones containing these genes in their entirety. In both cases, single open reading frames specifying basic proteins of 335 amino acid residues were predicted from the nucleotide sequences. Both viral messages were composed of approximately 1,450 nucleotides and contained 400 nucleotides of presumptive noncoding sequences at their respective 3' ends. MV and CDV M-protein-coding regions were 67% homologous at the nucleotide level and 76% homologous at the amino acid level. Only chance homology was observed in the 400-nucleotide trailer sequences. Comparisons of the M protein sequences of MV and CDV with the sequence reported for Sendai virus (B. M. Blumberg, K. Rose, M. G. Simona, L. Roux, C. Giorgi, and D. Kolakofsky, J. Virol. 52:656-663; Y. Hidaka, T. Kanda, K. Iwasaki, A. Nomoto, T. Shioda, and H. Shibuta, Nucleic Acids Res. 12:7965-7973) indicated the greatest homology among these M proteins in the carboxyterminal third of the molecule. Secondary-structure analyses of this shared region indicated a structurally conserved, hydrophobic sequence which possibly interacted with the lipid bilayer.

Amino Acid Sequence↗
PubMed1985

Cloning and characterization of DNA complementary to the canine distemper virus mRNA encoding matrix, phosphoprotein, and nucleocapsid protein.

Double-stranded cDNA synthesized from total polyadenylate-containing mRNA, extracted from monkey kidney cells infected with canine distemper virus (CDV), has been cloned into the PstI site of Escherichia coli plasmid pBR322. Clones containing canine distemper virus DNA were identified by hybridization to a canine distemper virus-specific, 32P-labeled cDNA. Four specific clones containing different classes of sequences have been identified. The cloned plasmids contain inserts of 800 (clone 44-80), 960 (clone 74-16), 1,700 (clone 364), and 950 (clone 40-9) base pairs. The sizes of the mRNA species complementary to these inserts are 1,500, 1,850, 1,850 and 2,500 nucleotides, respectively, as determined by the Northern technique. Three of the cloned DNA fragments were further identified as the reverse transcripts of the mRNA coding for the matrix, phosphoprotein, and nucleocapsid protein of CDV.

Base Sequence↗
PubMed1985

Measles virus P gene codes for two proteins.

The entirety of the phosphoprotein gene of measles virus has been sequenced. The gene is composed of 1,657 nucleotides and specifies a 507-amino-acid protein (P). A second overlapping reading frame was predicted from the sequence and specifies a 186-amino-acid protein (C). Through the use of antisynthetic peptide antibodies, we show that both proteins are expressed in virally infected cells. Both proteins are expressed from a functionally bicistronic mRNA through independent initiation of ribosomes at the respective AUG codons. Using immunofluorescent microscopy, we localized the C protein in the nucleus and in cytoplasmic inclusions within the infected cells.

Animals↗
PubMed1984

Positive identification of a measles virus cDNA clone encoding a region of the phosphoprotein.

A measles virus-specific cDNA clone, C1-G, that was previously assigned as a hemagglutinin-specific clone has been reassigned as a phosphoprotein-specific clone. The nucleotide sequence of C1-G was used to deduce the amino acid sequence. A synthetic peptide was constructed from a portion of the deduced sequence, and antisera were prepared. The antibodies directed against this synthetic peptide specifically precipitated the phosphoprotein of measles virus and not the hemagglutinin.

Amino Acid Sequence↗
PubMedDate not supplied

The analgesic efficacy of clodronate compared with placebo in patients with painful bone metastases from prostatic cancer.

Fifty-five patients with hormone refractory prostate cancer and painful bone metastases were randomised either to placebo or to clodronate 300 mg i.v. for 3 days, followed by oral clodronate 3200 mg for four weeks. Pain intensity was assessed using Visual Analogue Scales (VAS). Mean overall pain as well as mean pain during the best and worst periods were recorded. Forty-six patients were evaluable for efficacy. No significant differences were found between the two treatments. As regards mean worst pain a substantial numerical fall was registered for the treatment group, 21 mm, but the improvement was not significant compared to that of the placebo group. This was probably due to the limited number of patients (the study was prematurely ended due to problems recruiting patients). In conclusion, no significant differences were found between the treatment arm and the controls, in contrast to results from previous studies. Possible explanations are that the doses in this study were generally lower than in previous studies, the mean baseline pain was substantially lower and that the current study was placebocontrolled. Our data indicate that if clodronate is to be used for the alleviation of bone pain in prostate cancer, patients with high baseline should be selected and high intravenous doses should be given at start of the treatment.

Aged↗