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C Eklund

Publications and source records attributed to C Eklund.

34 records · Page 2Linked to original sources
PubMed1996

Surface conformational and linear epitopes on HPV-16 and HPV-18 L1 virus-like particles as defined by monoclonal antibodies.

A panel of 24 monoclonal antibodies (MAbs) was generated against human papillomavirus (HPV) types 16 and 18 L1 virus-like particles (VLPs). The MAbs were screened for reactivity to a variety of VLPs prepared from HPV-6, -11, -16, -18, -31, -33, -35, and -45, cottontail rabbit papillomavirus, bovine papillomavirus type 1, and a set of 35 overlapping 20-amino-acid peptides spanning the entire HPV-16 L1 gene. Type-specific linear and conformational surface epitopes were detected as well as several cross-reactive linear epitopes that showed various levels of cross-reactivity between different genital HPV and animal papillomavirus L1s. Most of the linear epitopes were mapped using synthetic peptides, and the epitopes were identified as being either surface or buried within the VLP as defined by the pattern of reactivity in ELISA using intact and disrupted VLP antigen. These MAbs may be useful reagents to help define neutralizing epitopes of HPV-16 and -18 when infectivity assays become available, and to define the regions of L1 that are exposed on the surface or buried within the assembled capsid.

Amino Acid Sequence↗
PubMed1995

Association of serum immunoglobulin G antibodies against human papillomavirus type 16 capsids with anal epidermoid carcinoma.

BACKGROUND: Anal epidermoid carcinoma is a relatively rare tumor, but its incidence has been increasing rapidly during the past few years. Genetic material from the major oncogenic types of human papillomavirus (HPV), types 16 and 18, has regularly been demonstrated in a substantial proportion of anal cancers, suggesting an etiologic role of HPV infection. Recently, serum antibodies against HPV type 16 capsids were shown to be a serologic measure of HPV16 infection. PURPOSE: We investigated whether serum antibodies against HPV16 capsids are associated with an increased risk of developing anal cancer. METHODS: Serum samples from 64 patients (48 women and 16 men) with untreated anal epidermoid cancer and from 79 age- and sex-matched healthy blood donors were analyzed for the levels of serum immunoglobulin G (IgG) against capsids of HPV16 by the enzyme-linked immunosorbent assay. The levels of serum IgG against HPV type 6 and bovine papillomavirus (BPV) capsids, as well as against HPV16 peptide antigens, were also measured. RESULTS: Whereas antibodies against HPV6 or BPV capsids were not significantly associated with anal cancer, the presence of IgG against HPV16 capsids exceeding the anti-BPV antibody levels was demonstrated among 55% (35 of 64) of the case patients but only among 4% (three of 79) of the control subjects (odds ratio [OR] = 30.4; 95% confidence interval [CI] = 8.4-161.5). Antibodies against HPV16 E2 and E7 peptides were also more common among case patients (OR = 12.8 and 95% CI = 5.4-31.5 for E2; OR = 3.0 and 95% CI = 1.4-6.7 for E7). CONCLUSION: The results suggest that HPV16 capsid antibodies are serologic markers for anal cancer. IMPLICATION: Exposure to HPV16 or related viruses appears to be a major risk factor in the majority of anal cancers.

Aged↗
PubMed1995

Antibodies against linear and conformational epitopes of human papillomavirus type 16 that independently associate with incident cervical cancer.

In a seroepidemiological study of incident cervical cancer, 94 cases and 188 population-based controls were used to evaluate the disease-association of IgG and IgA antibody responses against 6 human papillomavirus (HPV) type-16 antigens. Nine of the tested antibody responses were positively associated with cervical cancer, with odds ratios (ORs) ranging from 2.5 to 15.0. The antibody responses most strongly associated with cervical cancer were IgA against E6:10, an epitope derived from the carboxyterminal part of the HPV16 E6 [OR = 15.0, confidence intervals (CI) = 5.9-48.6], IgG against HPV16 virus-like particles (OR = 9.5, CI = 3.9-28.0) and IgG against the E1:19 epitope in the middle part of the E1 protein of HPV16 (OR = 7.7, C1 = 3.9-16.5). When the 3 serological assays that showed the strongest association with cervical cancer were combined, positivity for 2 assays was found among 52% of cases at an OR of 29.9. We conclude that antibody responses to several linear and conformational HPV epitopes are independently associated with cervical cancer and that combined analysis of several HPV antibody responses can result in better predictive values for HPV-associated cancer.

Age Factors↗
PubMed1995

A two-site enzyme immunoassay for quantitation of human papillomavirus type 16 particles.

A group of human papillomaviruses (HPV), in particular HPV type 16, are the major cause of anogenital dysplasias, which are precursors of anogenital cancer. The mode of transmission, extent of infectivity and natural history of infection are incompletely understood because methods to quantify shedding of viral particles have not been available. A two-site ELISA was developed to detect and quantify HPV-16 particles. Rabbits and guinea pigs were immunized with a series of peptides from the L1 and L2 capsid proteins of HPV-16. Among rabbit antipeptide sera tested for use as capture antibodies, only sera against one peptide bound detectable amounts of virus. Guinea pig antisera against several peptides were used as reporter antibodies to detect bound virus particles. If antisera against the same peptide were used both as capture antibody and reporter antibody, only intact particles were detected. Disrupted particles were quantified using antibodies against one L1 peptide as capture antibody and antibodies against other L1 peptides as reporter antibody. The lowest detectable amount of virus was 3 ng (0.06 micrograms/ml). There was no detectable cross-reaction with HPV type 6 or 11. The assay could be used both with cervical swabs in several common sample collection buffers and with surgical material solubilized in NP40-containing extraction buffers. Among 15 surgically removed condyloma acuminata, only 1 specimen was found to contain HPV-16 particles, at a concentration of 375 ng/ml (1.1 micrograms/specimen). Among 29 cervical swab samples from patients with koilocytotic atypia, 9 samples were found to contain virus. The results indicate that this assay is useful for large-scale studies on shedding of HPV particles.

Amino Acid Sequence↗
PubMed1995

Factors associated with successful withdrawal from methadone maintenance treatment in Sweden.

Two groups have been compared with each other with respect to the possible influence of a number of possible predictors of success in voluntary methadone withdrawal-one group that succeeded in terminating their methadone maintenance treatment and one group that did not manage to quit, despite serious attempts. Each of the groups contains 25 subjects. The possible predictors were subdivided into Conditions and Interventions. The results show that few Conditions exhibit any predictive value, while a larger proportion of the studied Interventions are associated with success.

Adult↗
PubMed1995

Association of serum antibodies against defined epitopes of human papillomavirus L1, E2, and E7 antigens and of HPV DNA with incident cervical cancer.

In order to provide a large-scale evaluation of the association with cervical cancer of antibodies against human papillomavirus (HPV) antigens, sera from 233 patients with primary, untreated cervical cancer and from 157 healthy age- and sex-matched blood donors were analyzed for IgG and IgA antibodies against HPV-derived peptide antigens and against bovine papillomavirus. Several serological responses were strongly associated with cervical cancer, notably the IgG response against the HPV 16 epitopes L1:13 (Relative risk [RR]: 5.3), E2:9 (RR: 2.9), and E7:5 (RR: 4.3), and the IgA response against an HPV 18 E2-derived antigen (245:18, RR: 3.1). HPV DNA in corresponding cervical tumors was analyzed by Southern blotting (SB) and polymerase chain reaction (PCR) in 47 patients. Sixty-six percent of the patients carried HPV DNA as determined by SB, 91% of patients analyzed by PCR. Neither the antibody responses, nor the presence of HPV DNA were significantly associated with the biological properties of the tumors.

Adult↗
PubMed1994

A population-based seroepidemiological study of cervical cancer.

The epidemiology of cervical cancer indicates the presence of a sexually transmitted risk factor, attributable at least in part to infection with human papillomavirus (HPV) type 16 or 18. We performed a seroepidemiological study of HPV and cervical cancer in the counties of Västerbotten and Norrbotten in Northern Sweden, a low-risk area for cervical cancer. Sera from 94 cases of incident cervical cancer were matched against 188 age- and sex-matched controls derived from a population-based blood bank. IgG and IgA antibodies were measured against a panel of 12 antigens derived from HPV types 6, 11, 16, or 18, as well as against Herpes simplex virus type 1 and 2, Chlamydia trachomatis, cytomegalovirus, Epstein-Barr virus, and bovine papillomavirus. Significantly increased relative risks (RRs) were found for IgG to HPV 16- or 18-derived antigens from the L1 (RR = 3.1), E2 (RRs = 2.8 and 9.2), and E7 (RRs = 3.8 and 2.7) open reading frames and for IgA to HPV 16-derived antigens from the E2 (RR = 3.3) and E6 (RR = 2.7) open reading frames. The highest RR (9.2, confidence intervals 4.4-19.4) was associated with IgG to an HPV 18 E2 antigen. Antibodies against cytomegalovirus, Herpes simplex virus type 2, Epstein-Barr virus, or bovine papillomavirus were, on their own, not significantly associated with cervical cancer, but seropositivity against multiple infections was associated with a successively increased relative risk. An increased risk was also found for IgG to Chlamydia trachomatis (RR = 1.7, confidence interval = 1.0-2.7). The results indicate that several HPV antibodies are strongly associated with cervical cancer, providing further seroepidemiological support for an etiological role of HPV in cervical cancer.

Adult↗
PubMed1994

A seroepidemiologic study of HPV infection and incident cervical squamous intraepithelial lesions.

The seroepidemiology of genital human papillomavirus (HPV) and incident cervical squamous intraepithelial lesions (SIL) was studied in subjects selected from a large cohort monitored for the development of SIL. Serum IgG and IgA responses to 10 epitopes derived from HPV were measured in 21 incident cases of SIL and 56 matched controls. Cases showed elevated antibody (i.e., IgG and/or IgA) seroprevalence to 245:16, a peptide antigen derived from the E2 open reading frame of HPV 16 (OR = 5.76; 95% CI: 1.24, 26.81). The type of HPV DNA detected in cervical lavage specimens had no effect on this relationship. Multivariate analysis also showed that IgG to 245:6, an analogous peptide derived from HPV 6, was negatively associated with SIL (OR = 0.12; 95% CI: 0.02, 0.77). No other antibody responses tested were associated with SIL. Furthermore, no antibody responses were positively associated with detection of HPV DNA in women without SIL. We conclude that incident SIL is positively associated with antibody to an epitope derived from the E2 region of HPV 16, and negatively associated with antibody to an analogous peptide derived from HPV 6. The seroepidemiology of incident SIL appears different from that of cervical HPV infection in the absence of SIL.

Adult↗
PubMed1994

Detoxification from methadone maintenance treatment in Sweden: long-term outcome and effects on quality of life and life situation.

Of 59 subjects who have undergone voluntary and serious attempts to terminate methadone maintenance treatment (MMT) within the framework of the Swedish methadone program, 50 could be reached for an interview. Of these, 25 were classified--with some reservations--as successful (Group 1), i.e., they lived opiate-free and to all appearances well-ordered lives. The other 25 had failed in their attempts (Group 2) and were all in methadone treatment, most functioning well. A comparison was made between the two groups with regard to change in perceived quality of life and actual life situation from the time before the detoxification attempts were begun (Period 1) until the time preceding the interview (Period 2). The results indicate that Group 1 has achieved a higher quality of life and a more stable actual life situation compared with Group 2.

Adaptation, Psychological↗
PubMed1994

Scanning the structure and antigenicity of HPV-16 E6 and E7 oncoproteins using antipeptide antibodies.

The structure and antigenicity of the HPV-16 E6 and E7 oncoproteins was studied using a set of antisera against overlapping synthetic peptides. We report that antigenic, mobile regions of the native proteins, as defined by reactivity with antipeptide antisera, occur at the N-termini of both E6 and E7 proteins, corresponding to regions of known or suspected protein-protein interactions. The putative zinc finger domains were consistently non-reactive, despite computer predictions of relatively high antigenicity, suggesting that the proposed zinc finger regions are held in stable secondary structures that the peptides were not able to mimic. In E6, the linker region between the two zinc fingers was antigenic, indicating that the two zinc finger structures might be able to articulate relative to one another by a flexible linker region. The highly antigenic N-terminal region of HPV-16 E7 was also found to be antigenic in E7 of both HPV-11 and HPV-18, indicating that the E7 proteins of different HPV types have similar antigenic structures. The identification of antigenic regions of the E6 and E7 proteins should be therefore be useful in the design of site-directed antibodies against E6 and E7 for numerous HPV types.

Amino Acid Sequence↗
PubMed1992

Levels of immunoglobulin G antibodies against defined epitopes of the L1 and L2 capsid proteins of human papillomavirus type 6 are elevated in men with a history of condylomata acuminata.

Sera from 159 men attending the sexually transmitted disease clinic at Karolinska Hospital, Stockholm, Sweden, were analyzed for the presence of immunoglobulin A (IgA) and IgG antibodies to a panel of synthetic peptides derived from the E2, L1, and L2 regions of the human papillomavirus types 1 (HPV 1), 6, 8, 11, 16, 18, 31, and 33. The study subjects were divided into three groups: (i) asymptomatic men with no history of genital warts who served as controls, (ii) men with visible condylomata, and (iii) men who had previously been afflicted with condylomata. There were no significant differences in antibody titers for any of the HPV 6- or 11-derived peptides among patients with current condylomata and the controls. For the peptide from L1 of HPV 6, there was an increase in the IgG titers among men with previous condylomata compared with the titers for the controls (52% versus 27% seropositivity; P less than 0.05). Also, for the peptide from L2 of HPV 6, there was an increase in the IgG titers among men who had been afflicted with condylomata previously (P less than 0.05). Increased IgA antibody titers against an HPV 16-derived peptide and an HPV 18-derived peptide were also detected. For the peptides from L1 and L2 of HPV 6, the study was extended to an additional group of 127 males attending the sexually transmitted disease clinic at Huddinge Hospital in southern Stockholm. Again, significantly increased antibody levels were detected only for IgG and only among asymptomatic men with a history of condylomata (P < 0.01 for the L1 peptide and P < 0.05 for the L2 peptide). The results suggest that the IgG response against the late proteins of HPV 6 reflects mainly previous exposure to the virus rather than ongoing viral disease.

Adolescent↗
PubMed1990

Mapping of linear epitopes of human papillomavirus type 16: the L1 and L2 open reading frames.

Certain types of human papillomavirus (HPV), notably HPV type 16, are associated with flat or inverted proliferative lesions of the cervix uteri that can progress to malignancy. As a first step towards the serological study of the epidemiology of HPV, we have synthesized the entire amino acid sequences of the 2 major viral capsid proteins of HPV type 16, L1 and L2, as a set of 66 synthetic 20-residue peptides with an overlap of 5 amino acids. The peptides were tested for reactivity with IgA, IgG and IgM antibodies in the sera of 30 patients with HPV-16-carrying cervical neoplasms. Both IgG and IgM antibody responses were detected, but most of the reactivity found was of the IgA class. The most immunoreactive peptides were further analyzed for reactivity with sera from 22 patients with parotid gland tumors and with sera from 38 healthy individuals. The L2-encoded protein contained only one major linear epitope, which was not specific for HPV-16-carrying neoplasms. In contrast, the L1-encoded protein contained several epitopes that were regularly immunoreactive with antibodies present in the sera of patients with HPV-16-carrying cervical neoplasms, but only rarely so in the sera of patients with other tumors or of healthy individuals.

Amino Acid Sequence↗
PubMed1962

ENZYME ASSOCIATED WITH BACTERIOPHAGE INFECTION.

Eklund, Curtis (The University of Texas, Austin) and Orville Wyss. Enzyme associated with bacteriophage infection. J. Bacteriol. 84:1209-1215. 1962.-A capsule-digesting enzyme was formed when azotobacter cells were infected with bacteriophage. The enzyme appeared in the medium when the phages lysed the cells. By disrupting phage-infected cells prematurely, it was shown that enzyme formation in the bacterium began shortly after invasion. The amount of enzyme formed was far in excess of that incorporated into the new phages. The enzyme was concentrated from the lysate, and its activity was measured under a variety of conditions.

Journal Article↗
PubMedDate not supplied

Determination of total sulfite in shrimp, potatoes, dried pineapple, and white wine by flow injection analysis: collaborative study.

A method for the determination of total sulfite in shrimp, potatoes, dried pineapple, and white wine by flow injection analysis (FIA) was collaboratively studied by 8 laboratories. In the method, the sample solution is reacted with sodium hydroxide to liberate aldehyde-bound sulfite. The sample stream is acidified to produce SO2 gas, which diffuses across a Teflon membrane in the gas diffusion cell into a flowing stream of malachite green. The degree of discoloration of the malachite green is proportional to the amount of sulfite in the sample solution. Red wine was included in the study but interlaboratory precision for these samples was not satisfactory and correlation with Monier-Williams results was poor. The present method is not recommended for use with these samples. For shrimp, potatoes, dried pineapple, and white wine, average reproducibility (RSDR) of results was 25% for samples at 10 ppm SO2 and 10% for samples at greater than 50 ppm. Overall average reproducibility was 14%. Recoveries of sulfite added to samples averaged 80%. Comparison of FIA with the Monier-Williams method indicated comparable results by the 2 methods. The FIA method has been adopted official first action for determination of greater than or equal to 5 ppm total sulfite in shrimp, potatoes, dried pineapple, and white wine.

Animals↗