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M Charles

Publications and source records attributed to M Charles.

At least 19 recordsLinked to original sources
PubMed1996

Use of chimeric human immunodeficiency virus types 1 and 2 reverse transcriptases for structure-function analysis and for mapping susceptibility to nonnucleoside inhibitors.

The human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2) reverse transcriptases (RTs) are evolutionary related. To study the effect of homologous sequence replacements on polymerase function and to map the determinants of the lack of susceptibility of HIV-2 RT to nonnucleoside drugs, a series of chimeric HIV-1/HIV-2 RTs were constructed. Analysis of the chimeric RTs showed that wild-type levels of RNA-dependent DNA polymerase activity were retained when both finger and palm subdomains were exchanged as a unit between the two parental RTs. Analysis of enzymatically active chimeras for inhibition by the thiobenzimidazolone derivative TIBO R82150 showed that a segment of HIV-2 RT at 212-250, when placed in the HIV-1 RT context, conferred a 40-fold decrease in susceptibility to TIBO R82150. Site-directed mutagenesis of this segment found Tyr227 to be a key residue in this segment for the natural resistance of HIV-2 RT to TIBO R82150.

Amino Acids↗
PubMed1996

Evolution of structure and substrate specificity in D-alanine:D-alanine ligases and related enzymes.

The D-alanine:D-alanine-ligase-related enzymes can have three preferential substrate specificities. Usually, these enzymes synthesize D-alanyl-D-alanine. In vancomycin-resistant Gram-positive bacteria, structurally related enzymes synthesize D-alanyl-D-lactate or d-alanyl-d-serine. The sequence of internal fragments of eight structural d-alanine:d-alanine ligase genes from enterococci has been determined. Alignment of the deduced amino acid sequences with those of other related enzymes from Gram-negative and Gram-positive bacteria revealed the presence of four distinct sequence patterns in the putative substrate-binding sites, each correlating with specificity to a particular substrate (D-alanine:D-lactate ligases exhibited two patterns). Phylogenetic analysis showed different clusters. The enterococcal subtree was largely superimposable on that derived from 16S rRNA sequences. In lactic acid bacteria, structural divergence due to differences in substrate specificity was observed. Glycopeptide resistance proteins VanA and VanB, the VanC-type ligases, and DdlA and DdlB from enteric bacteria and Haemophilus influenzae constituted separate clusters.

Amino Acid Sequence↗
PubMed1995

[Gallbladder cancer. Case-control study].

Gallbladder cancer is the principal oncological cause of death in chilean women and cholelithiasis is a well recognized risk factor. Aiming to unravel other risk factors for gallbladder cancer, we compared 50 patients subjected to cholecystectomy in whom a gallbladder cancer was found with 50 age and sex matched operated controls without cancer. Subjects were clinically assessed and interrogated about demographic, obstetrical features and feeding features. Multiples and early pregnancies were factors significantly associated to the development of gallbladder cancer. Twenty subjects (44%) with cancer knew that they had cholelithiasis and 41 patients in each group were symptomatic. It is concluded that pregnancy may be a risk factor for gallbladder cancer probably due to the lithogenic effect of its hormonal changes. Also, early cholecystectomy in symptomatic individuals may be an effective preventive measure.

Adult↗
PubMed1994

Resistance to neutralization by broadly reactive antibodies to the human immunodeficiency virus type 1 gp120 glycoprotein conferred by a gp41 amino acid change.

A neutralization-resistant variant of human immunodeficiency virus type 1 (HIV-1) that emerged during in vitro propagation of the virus in the presence of neutralizing serum from an infected individual has been described. A threonine-for-alanine substitution at position 582 in the gp41 transmembrane envelope glycoprotein of the variant virus was responsible for the neutralization-resistant phenotype (M.S. Reitz, Jr., C. Wilson, C. Naugle, R. C. Gallo, and M. Robert-Guroff, Cell 54:57-63, 1988). The mutant virus also exhibited reduced sensitivity to neutralization by 30% of HIV-1-positive sera that neutralized the parental virus, suggesting that a significant fraction of the neutralizing activity within these sera can be affected by the amino acid change in gp41 (C. Wilson, M. S. Reitz, Jr., K. Aldrich, P. J. Klasse, J. Blomberg, R. C. Gallo, and M. Robert-Guroff, J. Virol. 64:3240-3248, 1990). It is shown here that the change of alanine 582 to threonine specifically confers resistance to neutralizing by antibodies directed against both groups of discontinuous, conserved epitopes related to the CD4 binding site on the gp120 exterior envelope glycoprotein. Only minor differences in binding of these antibodies to wild-type and mutant envelope glycoproteins were observed. Thus, the antigenic structure of gp120 can be subtly affected by an amino acid change in gp41, with important consequences for sensitivity to neutralization.

Animals↗
PubMed1994

Culture, drug abuse and some reflections on the family.

The authors recently completed a set of monographs on culture and drug use and abuse in a tribal district in Gujarat in western India where changes have occurred in alcohol consumption, two districts in Karnataka in south India where widespread use of cannabis is prevalent, six districts of Gujarat where extensive opium drinking is common, and also on the drug abuse situation in Goa, Delhi and Bombay. On the basis of those studies, the authors call for decentralized planning and a review of the Single Convention on Narcotic Drugs of 1961, and they critique some of the dominant practices in contemporary prevention and rehabilitation of addicts. The role of the family is examined as a socialization institution for transmittal of culture. The limits posed by patriarchy on the extent to which the family can be an agent of primary or secondary prevention of drug use and abuse are indicated.

Culture↗
PubMed1993

Probing the structure of the V2 domain of human immunodeficiency virus type 1 surface glycoprotein gp120 with a panel of eight monoclonal antibodies: human immune response to the V1 and V2 domains.

We have analyzed a panel of eight murine monoclonal antibodies (MAbs) that depend on the V2 domain for binding to human immunodeficiency virus type 1 (HIV-1) gp120. Each MAb is sensitive to amino acid changes within V2, and some are affected by substitutions elsewhere. With one exception, the MAbs were not reactive with peptides from the V2 region, or only poorly so. Hence their ability to bind recombinant strain IIIB gp120 depended on the preservation of native structure. Three MAbs cross-reacted with strain RF gp120, but only one cross-reacted with MN gp120, and none bound SF-2 gp120. Four MAbs neutralized HIV-1 IIIB with various potencies, and the one able to bind MN gp120 neutralized that virus. Peptide serology indicated that antibodies cross-reactive with the HxB2 V1 and V2 regions are rarely present in HIV-1-positive sera, but the relatively conserved segment between the V1 and V2 loops was recognized by antibodies in a significant fraction of sera. Antibodies able to block the binding of V2 MAbs to IIIB or MN gp120 rarely exist in sera from HIV-1-infected humans; more common in these sera are antibodies that enhance the binding of V2 MAbs to gp120. This enhancement effect of HIV-1-positive sera can be mimicked by several human MAbs to different discontinuous gp120 epitopes. Soluble CD4 enhanced binding of one V2 MAb to oligomeric gp120 but not to monomeric gp120, perhaps by inducing conformational changes in the oligomer.

Amino Acid Sequence↗
PubMed1993

Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding.

Interaction with the CD4 receptor enhances the exposure on the human immunodeficiency type 1 gp120 exterior envelope glycoprotein of conserved, conformation-dependent epitopes recognized by the 17b and 48d neutralizing monoclonal antibodies. The 17b and 48d antibodies compete with anti-CD4 binding antibodies such as 15e or 21h, which recognize discontinuous gp120 sequences near the CD4 binding region. To characterize the 17b and 48d epitopes, a panel of human immunodeficiency virus type 1 gp120 mutants was tested for recognition by these antibodies in the absence or presence of soluble CD4. Single amino acid changes in five discontinuous, conserved, and generally hydrophobic regions of the gp120 glycoprotein resulted in decreased recognition and neutralization by the 17b and 48d antibodies. Some of these regions overlap those previously shown to be important for binding of the 15e and 21h antibodies or for CD4 binding. These results suggest that discontinuous, conserved epitopes proximal to the binding sites for both CD4 and anti-CD4 binding antibodies become better exposed upon CD4 binding and can serve as targets for neutralizing antibodies.

Amino Acid Sequence↗
PubMed1993

Immunochemical analysis of the gp120 surface glycoprotein of human immunodeficiency virus type 1: probing the structure of the C4 and V4 domains and the interaction of the C4 domain with the V3 loop.

We have probed the structure of the C4 and V3 domains of human immunodeficiency virus type 1 gp120 by immunochemical techniques. Monoclonal antibodies (MAbs) recognizing an exposed gp120 sequence, (E/K)VGKAMYAPP, in C4 were differentially sensitive to denaturation of gp120, implying a conformational component to some of the epitopes. The MAbs recognizing conformation-sensitive C4 structures failed to bind to a gp120 mutant with an alteration in the sequence of the V3 loop, and their binding to gp120 was inhibited by both V3 and C4 MAbs. This implies an interaction between the V3 and C4 regions of gp120, which is supported by the observation that the binding of some MAbs to the V3 loop was often enhanced by amino acid changes in an around the C4 region.

Amino Acid Sequence↗
PubMed1993

Characterization of neutralizing monoclonal antibodies to linear and conformation-dependent epitopes within the first and second variable domains of human immunodeficiency virus type 1 gp120.

A number of linear and conformation-dependent neutralizing monoclonal antibodies (MAbs) have been mapped to the first and second variable (V1 and V2) domains of human immunodeficiency virus type 1 (HIV-1) gp120. The majority of these MAbs are as effective at neutralizing HIV-1 infectivity as MAbs to the V3 domain and the CD4 binding site. The linear MAbs bind to amino acid residues 162 to 171, and changes at residues 183/184 (PI/SG) and 191/192/193 (YSL/GSS) within the V2 domain abrogate the binding of the two conformation-dependent MAbs, 11/68b and CRA-4, respectively. Surprisingly, a change at residue 435 (Y/H or Y/S), in a region of gp120 near the CD4 binding site (M. Kowalski, J. Potz, L. Basiripour, T. Dorfman, W. C. Goh, E. Terwilliger, A. Dayton, C. Rosen, W. Haseltine, and J. Sodroski, Science 237:1351-1355, 1987; L. A. Lasky, G. M. Nakamura, D. H. Smith, C. Fennie, C. Shimasaki, E. Patzer, P. Berman, T. Gregory, and D. Capon, Cell 50:975-985, 1987; and U. Olshevsky, E. Helseth, C. Furman, J. Li, W. Haseltine, and J. Sodroski, J. Virol. 64:5701-5707, 1990), abrogated gp120 recognition by both of the conformation-dependent MAbs. However, both MAbs 11/68b and CRA-4 were able to bind to HIV-1 V1V2 chimeric fusion proteins expressing the V1V2 domains in the absence of C4, suggesting that residues in C4 are not components of the epitopes but that amino acid changes in C4 may affect the structure of the V1V2 domains. This is consistent with the ability of soluble CD4 to block 11/68b and CRA-4 binding to both native cell surface-expressed gp120 and recombinant gp120 and suggests that the binding of the neutralizing MAbs to the virus occurs prior to receptor interaction. Since the reciprocal inhibition, i.e., antibody inhibition of CD4-gp120 binding, was not observed, the mechanism of neutralization is probably not a blockade of virus-receptor interaction. Finally, we demonstrate that linear sequences from the V2 region are immunogenic in HIV-1-infected individuals, suggesting that the primary neutralizing response may be directed to both V2 and V3 epitopes.

Amino Acid Sequence↗
PubMed1993

[Epidemiologic and nutritional characteristics of the elderly].

A sample of 1365 elders of both sexes from rural and urban populations was studied. Thirty four percent of the subjects were older that 80 years. 21.6% lived alone, 25% were illiterate and 50% did not finish elementary school. Mental impairment was found in 5.6% and body mass index was normal in 41.4% of subjects. Eighty seven percent did not smoke and 80% were teetotalers. Medical services were requested at least every one year by 15.4% and twice a year by 11.9% of subjects. These numbers will help to design preventive and interventional policies directed to this segment of the population.

Aged↗
PubMed1991

Wound compression pads are of no value after local anaesthetic breast biopsy.

In a randomised study of 120 patients undergoing breast biopsy, wound compression pads did not reduce the frequency of postoperative bruising or haematoma formation, and 12% of the 62 patients having pads had complaints regarding their use. Wound compression pads are of no value after local anaesthetic breast biopsy.

Anesthesia, Local↗
PubMed1990

The use of on-line sensors in bioprocess control.

Commercialization of the products of biotechnology will require a continued emphasis on bioprocess design and scale-up. The use of process automation and control will help to meet the specifications of quality, safety, and cost. In the past, the application of process monitoring and control to biological processes has been limited by the availability of suitable sensors. New developments have combined the tools of microelectronics and molecular biology to address some of these limitations. Continued developments in this area will require close cooperation between microbiologists and process engineers to best apply these new tools. A general understanding of the concepts of process control, as they relate to biological processes, will contribute to that cooperation.

Biosensing Techniques↗
PubMed1990

[Cysts of the thoracic canal. Apropos of a subclavicular site].

The authors report a case of cystic dilatation of the terminal portion of the thoracic duct which clinically corresponded to a swelling in the root of the left side of the neck. Pathogeny and evolutive mode of this exceptional affection are ill known. Echography and scanography show the cystic nature of the mass. Diagnosis is made by direct puncture which can prove the chylous nature of the content and permits the opacification of the cyst. Lymphography shows the type of junction with the thoracic duct.

Adolescent↗
PubMed1988

Accuracy of rotavirus diagnosis: modified genome electrophoresis versus electron microscopy.

530 human faecal samples were examined for the presence of rotavirus by electron microscopy (EM) and by a modified electrophoretic analysis of viral genome (PAGE). 516 stools gave identical results by both methods (97.4% agreement). The proportion of EM+, PAGE- samples (1/530) was significantly lower than the proportion of EM-, PAGE + samples (13/530) (P less than 0.01 with McNemar test). Relative sensitivity was 99.6% for PAGE and 95% for EM. False positive results could be excluded for each method because of the characteristic morphology of rotavirus particles (EM) and specificity of rotavirus electrophoretypes (PAGE). Discrepant cases were reexamined whenever possible and the causes of misdiagnosis are discussed.

Electrophoresis, Polyacrylamide Gel↗