Biomedical subjects

A M Beckmann

Publications and source records attributed to A M Beckmann.

At least 19 recordsLinked to original sources

PubMed2000

Sequential increase in Egr-1 and AP-1 DNA binding activity in the dentate gyrus following the induction of long-term potentiation.

Establishment of long-term potentiation (LTP) at perforant path synapses is highly correlated with increased expression of Egr and AP-1 transcription factors in rat dentate gyrus granule cells. We have investigated whether increased transcription factor levels are reflected in increased transcription factor activity by assessing Egr and AP-1 DNA binding activity using gel shift assays. LTP produced an increase in binding to the Egr element, which was NMDA receptor-dependent and correlated closely with our previously reported increase in Egr-1 (zif/268) protein levels. Supershift analysis confirmed involvement of Egr-1, but not Egr-2 in the DNA binding activity. AP-1 DNA binding was also rapidly elevated in parallel with protein levels, however, the peak increase in activity was delayed until 4 h, a time point when we have previously shown that only jun-D protein was elevated. These data indicate that binding of Egr-1 and AP-1 to their response elements is increased in two phases. This may result in activation of distinct banks of target genes which contribute to the establishment of persistent LTP.

Animals↗

PubMed1999

Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine.

Acute exposure to cocaine transiently induces several Fos family transcription factors in the nucleus accumbens, a region of the brain that is important for addiction. In contrast, chronic exposure to cocaine does not induce these proteins, but instead causes the persistent expression of highly stable isoforms of deltaFosB. deltaFosB is also induced in the nucleus accumbens by repeated exposure to other drugs of abuse, including amphetamine, morphine, nicotine and phencyclidine. The sustained accumulation of deltaFosB in the nucleus accumbens indicates that this transcription factor may mediate some of the persistent neural and behavioural plasticity that accompanies chronic drug exposure. Using transgenic mice in which deltaFosB can be induced in adults in the subset of nucleus accumbens neurons in which cocaine induces the protein, we show that deltaFosB expression increases the responsiveness of an animal to the rewarding and locomotor-activating effects of cocaine. These effects of deltaFosB appear to be mediated partly by induction of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole) glutamate receptor subunit GluR2 in the nucleus accumbens. These results support a model in which deltaFosB, by altering gene expression, enhances sensitivity to cocaine and may thereby contribute to cocaine addiction.

Animals↗

PubMed1998

Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection.

BACKGROUND: Experimental models and analyses of human tumors suggest that oncogenic, sexually transmittable human papillomaviruses (HPVs) are etiologic factors in the development of oral squamous cell carcinoma (SCC). We conducted a population-based, case-control study to determine whether the risk of this cancer is related to HPV infection and sexual history factors. METHODS: Case subjects (n = 284) were 18-65-year-old residents of three counties in western Washington State who were newly diagnosed with oral SCC from 1990 through 1995. Control subjects (n = 477) similar in age and sex were selected from the general population. Serum samples were tested for HPV type 16 capsid antibodies. Exfoliated oral tissue collected from case and control subjects and tumor tissue from case subjects were tested for HPV DNA. Odds ratios (ORs) were calculated after adjusting for age, sex, cigarette smoking, and alcohol consumption. RESULTS: Among males only, oral SCC risk increased with self-reported decreasing age at first intercourse, increasing number of sex partners, and a history of genital warts. Approximately 26% of the tumors in case subjects contained HPV DNA; 16.5% of the tumors contained HPV type 16 DNA. The prevalence of oncogenic HPV types in exfoliated oral tissue was similar in case and control subjects. The ORs for HPV type 16 capsid seropositivity were 2.3 (95% confidence interval [CI] = 1.6-3.3) for all oral SCCs and 6.8 (95% CI = 3.0-15.2) for oral SCCs containing HPV type 16 DNA. The joint association of cigarette smoking and HPV type 16 capsid seropositivity with oral SCC (OR = 8.5; 95% CI = 5.1-14.4) was stronger than predicted from the sum of individual associations with current smoking (OR = 3.2; 95% CI = 2.0-5.2) and seropositivity (OR = 1.7; 95% CI = 1.1-2.6). CONCLUSIONS: HPV type 16 infection may contribute to the development of a small proportion of oral SCCs in this population, most likely in combination with cigarette smoking.

Adult↗

PubMed1998

Loss of heterozygosity at 5q21-22 (adenomatous polyposis coli gene region) in oral squamous cell carcinoma is common and correlated with advanced disease.

We determined the frequency of loss of heterozygosity (LOH) at chromosome 5q21-22 (adenomatous polyposis gene region) in oral SCC from 49 patients using PCR-based assays. Of 43 informative (heterozygous) tumors, 41.9% [95% confidence interval (CI)=27.0, 57.9] contained LOH at 5q21-22. LOH at 5q21-22 was strongly associated with stage at diagnosis: 100%, (3/3), 50% (13/26), and 14% (2/14) of tumors from patients with distant metastases, regional spread, and localized disease, respectively, contained this genetic alteration (P=0.01). There were no statistically significant associations between LOH at 5q21-22 and other patient or tumor characteristics, but LOH was more commonly found in the tumors of heavy smokers, infrequent alcohol consumers, and in tumors containing either p53 mutations or HPV-DNA. In univariate analyses, LOH at 5q21-22 was associated with poor prognosis (hazard ratio=1.8, 95%, CI 0.8, 4.5); this relationship did not persist after adjustment for stage of disease (hazard ratio=1.1, 95% CI=0.4, 3.1). These data provide further evidence that inactivation of the APC gene and/or other genes at 5q21-22 is common and may be involved in the development and/or progression of oral SCC. Larger studies are needed to determine whether LOH at 5q21-22 is linked to known oral SCC etiologic factors and/or the prognosis of oral SCC patients, as well as to genetic instability at other loci involved in these malignancies.

Adult↗

PubMed1997

Cofactors with human papillomavirus in a population-based study of vulvar cancer.

BACKGROUND: Human papillomavirus (HPV) has been previously associated with vulvar cancer. In a population-based study, we examined whether exposure to HPV, cigarette smoking, or herpes simplex virus 2 (HSV2) increases the risk of this cancer. METHODS: Incident cases of in situ (n = 400) and invasive (n = 110) squamous cell vulvar cancer diagnosed among women living in the Seattle area from 1980 through 1994 were identified. Serum samples were analyzed for antibodies against specific HPV types and HSV2. HPV DNA in tumor tissue was detected by means of the polymerase chain reaction. In most analyses, case subjects were compared with population-based control subjects (n = 1403). Relative risks of developing vulvar cancer were estimated by use of adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Increased risks of in situ or invasive vulvar cancer were associated with HPV16 seropositivity (ORs = 3.6 [95% CI = 2.6-4.8] and 2.8 [95% CI = 1.7-4.7], respectively), current cigarette smoking (ORs = 6.4 [95% CI = 4.4-9.3] and 3.0 [95% CI = 1.7-5.3], respectively), and HSV2 seropositivity (ORs = 1.9 [95% CI = 1.4-2.6] and 1.5 [95% CI = 0.9-2.6], respectively). When the analysis was restricted to HPV16 DNA-positive tumors (in situ or invasive), the OR associated with HPV16 seropositivity was 4.5 (95% CI = 3.0-6.8). The OR for vulvar cancer was 18.8 (95% CI = 11.9-29.8) among current smokers who were HPV16 seropositive in comparison with never smokers who were HPV16 seronegative. CONCLUSIONS: Current smoking, infection with HPV16, and infection with HSV2 are risk factors for vulvar cancer. Risk appears particularly strong among women who are both current smokers and HPV16 seropositive.

Adult↗

PubMed1997

Human papillomavirus type 16 DNA in esophageal carcinomas from Alaska Natives.

The possible etiological role of human papillomavirus (HPV) in esophageal carcinogenesis was evaluated in Alaska Natives in whom the incidence of esophageal cancer is 1.3 and 3.8 times higher than in US Caucasian men and women, respectively. Fixed paraffin-embedded esophageal tissues from 32 cases of squamous-cell carcinoma (SCC) and 3 cases of adenocarcinoma (AC) diagnosed between 1957 and 1988 were analyzed by polymerase chain reaction (PCR) and in situ hybridization for HPV DNA sequences. Detection of the human beta-globin gene by PCR was used as a control for sufficiency of DNA and its potential for amplification in the tissue samples. Twenty-five of the tumor tissues were considered adequate for PCR analyses; HPV DNA was detected in 10 of 22 SCCs and was not found in 3 ACs. Seven of the 10 HPV-positive tissues contained sequences from the E6 gene of HPV type 16. Koilocytosis, an epithelial change consistent with HPV infection, was found in 80% of the esophageal squamous-cell tumors with HPV DNA and in 75% of those without HPV DNA. The detection of amplifiable cellular DNA was related to recentness of diagnosis; however, the detection of HPV DNA within amplifiable specimens was not related to recentness of diagnosis. A 413-bp sequence from the L1 open reading frame of HPV 16 from esophageal tissue of 2 patients was identical to sequences previously identified in cervical cells from other Alaska Natives. Our results provide molecular evidence of HPV infection, especially type 16, in archival esophageal cancer tissues from 45% of those patients whose specimens contain adequate DNA for PCR analysis.

Adenocarcinoma↗

PubMed1997

Human papillomavirus types 52 and 58 are prevalent in cervical cancers from Chinese women.

A substantial body of evidence has confirmed human papillomavirus (HPV) infection as an etiologic agent in human cervical cancer. To evaluate the association between HPV and cervical cancer in Chinese women, we examined tumor specimens from women who lived in Shanghai, People's Republic of China. Biopsies from 40 women, diagnosed with either squamous-cell carcinoma (n = 35) or adenocarcinoma (n = 5) were tested for HPV DNA by PCR. The HPV types present in tumors were determined either by hybridization of PCR products with HPV type-specific probes or by PCR-based sequencing. A total of 35 of the 40 cervical cancer specimens (87.5%) contained HPV DNA. The following distribution and types were detected: 7.5% HPV 16, 10% HPV 18, 20% HPVs 16 and 18, 15% HPV 52, 15% HPV 58, 12.5% HPVs 52 and 58 and 7.5% unclassified HPVs. In this population of Chinese women with cervical cancer, HPV 52 and 58 were as prevalent as the "high-risk" (for cervical cancer) viruses HPVs 16 and 18.

Adenocarcinoma↗

PubMed1997

Egr transcription factors in the nervous system.

The Egr proteins, Egr-1, Egr-2, Egr-3 and Egr-4, are closely related members of a subclass of immediate early gene-encoded, inducible transcription factors. They share a highly homologous DNA-binding domain which recognises an identical DNA response element. In addition, they have several less-well conserved structural features in common. As immediate early proteins, the Egr transcription factors are rapidly induced by diverse extracellular stimuli within the nervous system in a discretely controlled manner. The basal expression of the Egr proteins in the developing and adult rat brain and the induction of Egr proteins by neurotransmitter analogue stimulation, physiological mimetic and brain injury paradigms is reviewed. We review evidence indicating that Egr proteins are subject to tight differential control through diverse mechanisms at several levels of regulation. These include transcriptional, translational and post-translational (including glycosylation, phosphorylation and redox) mechanisms and protein-protein interaction. Ultimately the differentially co-ordinated Egr response may lead to discrete effects on target gene expression. Some of the known target genes of Egr proteins and functions of the Egr proteins in different cell types are also highlighted. Future directions for research into the control and function of the different Egr proteins are also explored.

Animals↗

PubMed1997

AP-1 and Egr DNA-binding activities are increased in rat brain during ethanol withdrawal.

The DNA-binding activities of AP-1 and Egr proteins were investigated in nuclear extracts of rat brain regions during ethanol withdrawal. Both DNA-binding activities were transiently elevated in the hippocampus and cerebellum 16 h after withdrawal. In the cerebral cortex, AP-1 and Egr DNA-binding activities increased at 16 h and persisted until 32 and 72 h, respectively. The AP-1 DNA-binding activities in all regions at all times after withdrawal were composed of FosB, c-Jun, JunB, and JunD. c-Fos was detected at all times in the cerebral cortex, at 16 h only in the hippocampus, and from 16 to 72 h in the cerebellum. Withdrawal severity did not affect the composition of the AP-1 DNA-binding activities. Two Egr DNA-binding activities were present in the cortex and hippocampus. The faster-migrating complex predominated in hippocampus, and only the slower-migrating complex (identified as Egr-1) was present in the cerebellum. The increase in DNA-binding activity of immediate early gene-encoded transcription factors supports their proposed role in initiating a cascade of altered gene expression underlying the long-term neuronal response to ethanol withdrawal.

Alcohol Withdrawal Delirium↗

PubMed1997

Differential expression of Egr-1-like DNA-binding activities in the naive rat brain and after excitatory stimulation.

Egr-1 and related proteins are inducible transcription factors within the brain recognizing the same consensus DNA sequence. Three Egr DNA-binding activities were observed in regions of the naive rat brain. Egr-1 was present in all brain regions examined. Bands composed, at least in part, of Egr-2 and Egr-3 were present in different relative amounts in the cerebral cortex, striatum, hippocampus, thalamus, and midbrain. All had similar affinity and specificity for the Egr consensus DNA recognition sequence. Administration of the convulsants NMDA, kainate, and pentylenetetrazole differentially induced Egr-1 and Egr-2/3 DNA-binding activities in the cerebral cortex, hippocampus, and cerebellum. All convulsants induced Egr-1 and Egr-2 immunoreactivity in the cerebral cortex and hippocampus. These data indicate that the members of the Egr family are regulated at different levels and may interact at promoters containing the Egr consensus sequence to fine tune a program of gene expression resulting from excitatory stimuli.

Animals↗

PubMed1996

Human papilloma viruses and p53 mutations in normal pre-malignant and malignant oral epithelia.

HPV infections have been previously observed in oral cancers, and inactivation of the p53 gene has been shown to be one of the most common genetic alterations in human tumors. We examined 179 oral specimens from 70 individuals with histologic findings of either normal mucosa (n = 6) or oral disease that ranged from mild dysplasia to invasive squamous-cell carcinoma (n = 64) to determine the occurrence of both HPV infection and p53 mutations and their relationship with several clinical factors. HPV infection was detected by PCR amplification of viral DNA, and the presence of p53 mutations was assayed using the single-strand conformation polymorphism (SSCP)-PCR technique. HPV infection was found in 31% of individuals with oral disease and was not seen in healthy individuals. Mutations in exons 5, 6, 7 or 8 of the p53 gene were detected in 37.5% of patients with oral lesions and in a biopsy from 1 healthy individual who was a heavy smoker. Approximately one-third of lesions classified as pre-malignant (dysplasia and carcinoma in situ) and 42% of invasive carcinomas contained p53 mutations. The majority of these mutations were G:T transversions located within exons 7 and 8. Tumor tissues from 6 patients with oral lesions were found both to be HPV-16-positive and to contain p53 mutations; of these, 4 were poorly differentiated carcinomas that were diagnosed as late-stage disease. In this study, p53 mutations were detected in the early stages of cancer development.

Aged↗

PubMed1996

Loss of the adenomatous polyposis coli gene and human papillomavirus infection in oral carcinogenesis.

Recent evidence suggests that loss of heterozygosity (LOH) of the adenomatous polyposis coli (APC) gene plays a role in colorectal tumorigenesis and other cancers. However, little is known as to whether the APC gene contributes to the pathogenesis of oral squamous cell carcinoma. To assess involvement of both the APC gene and the human papillomavirus (HPV) in the development of oral pre-malignant and malignant lesions, we analysed DNA from 14 paired oral normal and pre-malignant or malignant paraffin-embedded biopsy specimens, and DNA from cultured normal and HPV 16-immortalised oral epithelial cells for the presence of LOH of APC and for HPV infection, using PCR based techniques. LOH of APC occurred in 80% of cases of oral epithelial dysplasia, 67% of carcinoma in situ, 50% of invasive squamous cell carcinoma cases, and in the HPV 16-immortalised oral epithelial cells. HPV was detected in half of the biopsy specimens, with HPV 16 as the dominant type. More than half of the carcinoma cases were found to contain both LOH of APC and HPV infection. These results suggest that LOH of APC is an early event during oral tumorigenesis. Our findings also suggest a strong correlation between HPV infection, particularly HPV 16, and LOH of the APC gene in oral squamous cell carcinomas.

Cell Transformation, Neoplastic↗

PubMed1996

The relationship of human papillomavirus-related cervical tumors to cigarette smoking, oral contraceptive use, and prior herpes simplex virus type 2 infection.

It has now been established that infection with human papillomavirus (HPV) is necessary for the development of most cervical cancers. HPV is not sufficient for the development of cancer. Other exposures or host factors are necessary for cancer to occur. As part of an ongoing, population-based case-control study of invasive cervical cancer, we investigated the role of cigarette smoking, oral contraceptive (OC) use, and herpes simplex virus type 2 (HSV-2) as potential cofactors with HPV in the development of cervical cancer. Residents of three counties in western Washington State who were diagnosed with invasive squamous cell cervical cancer (n = 314) from January 1986 through December 1992 were interviewed about their sexual, reproductive, contraceptive, and cigarette smoking histories. Similar information was obtained from control women identified through random digit dialing (n = 672). The sera from 206 cases and 522 controls were tested for both HPV 16 capsid antibodies and HSV-2 antibodies. PCR was used to test paraffin-embedded tumor tissues for the presence of HPV DNA types 6, 16, 18, 31, 33, 35, and 39. Women with cervical cancer were more likely to be current smokers at diagnosis than population controls [relative risk (RR), 2.5; 95% confidence interval (CI), 1.8-3.4]. The risk associated with smoking was present to a similar extent among women positive and negative for HPV as measured by HPV 16 capsid antibodies and HPV DNA in the tumor tissue (cases). OC use was only important if first use was at an early age, particularly ages < or = 17 years (RR, 2.3; 95% CI, 1.4-3.8). There was only a slight risk for cervical cancer associated with antibodies to HSV-2 (RR, 1.2; 95% CI, 0.9-1.7). However, when we stratified by markers of HPV exposure, we found a significant increase in risk associated with HSV-2 among women negative for HPV 16 antibodies (RR, 2.0; 95% CI, 1.3-3.0), which was strengthened when we confined our analysis to cases whose tumors were HPV DNA negative (RR, 3.6; 95% CI, 1.6-8.0). There was no indication that cigarette smoking, OC use, or HSV-2 infection influence the ability of HPV infection to cause invasive cervical cancer. OC use may only be important in the etiology of invasive squamous cell cervical tumors if the use occurs at a critical time in the development of a woman's reproductive tract, at ages < or = 17 years. The majority of risk associated with HSV-2 was confined to HPV-negative tumors, indicating a possible separate pathway to disease that may account for 5-10% of invasive cervical cancers.

Adolescent↗

PubMed1996

Associations between human leukocyte antigen type and nasopharyngeal carcinoma in Caucasians in the United States.

A genetic component to nasopharyngeal carcinoma (NPC) has been suggested by associations of the malignancy with human leukocyte antigens (HLAs) in Southern Chinese populations, among which NPC is a major cancer. Data from other races are inconclusive. We have investigated associations between NPC and HLA antigens at the HLA-A, B, C, and DQ loci and alleles at the DRB1 locus in a population-based, multicenter investigation in the United States. Data from 82 cases and 140 controls are presented, making this the largest study population analyzing data from Caucasians to date. HLA frequencies from study cases were also compared with external control groups from the 11th International Histocompatibility Workshop and the National Marrow Donor Program. Logistic regression methods were used to investigate the effects of the joint occurrence of multiple HLA types and to assay for differences in HLA-associated risk in different age groups. A meta-analysis was undertaken to compare and summarize our results with previously published findings. The meta-analysis found a protective association with A2 antigen in non-Chinese [odds ratio (OR), 0.63; P < 0.001], a protective association with A11 across all races (OR, 0.54; P < 0.001), and an increased risk associated with B5 in Caucasians (OR, 2.81; P < 0.001). The present study also found independent associations, in a logistic regression model, between NPC and DRB1*1501 (OR, 0.33), DRB1*0405 (OR, 7.57), and Cw3 (OR, 0.42), although these data must be interpreted cautiously due to multiple-testing considerations. Associations were found to be more pronounced in younger patients for A2, A11, A28, B8, and B51.

Adult↗

PubMed1995

Immediate early gene expression during morphine withdrawal.

The expression of immediate early genes (IEG)s c-fos, c-jun and zif/268 was studied during naloxone-precipitated morphine withdrawal in various organs of the rat. Dependence was induced over a period of 6 days by a graded regimen of 6-hourly injections. Northern analysis revealed peak expression of all IEGs occurred in the forebrain plus cerebellum at 20 min and at 60 min in the brain stem following morphine withdrawal. Increased levels of c-fos and c-jun mRNA were observed in the spinal cord at 40 min of morphine withdrawal. An increase in c-fos and c-jun but not zif/268 mRNAs was seen in the jejunum between 20 and 60 min. Elevated levels of the IEG protein products in the cerebral cortex, hippocampus, thalamus, cerebellum, brain stem and spinal cord were observed at 60 min following morphine withdrawal. These data emphasize the temporal and spatial variation in IEG expression in different tissues during opiate withdrawal.

Animals↗

PubMed1994

Elevated AP-1 DNA-binding activity in rat brain during ethanol withdrawal.

The DNA-binding activity of the transcription factors AP-1, CREB and OCT was investigated in nuclear extracts of brains from rats undergoing ethanol withdrawal. AP-1 DNA-binding activity but not that of CREB or OCT was increased in the cerebral cortex, hippocampus and cerebellum 15 and 17 hr after ethanol withdrawal. A similar increase in AP-1 binding activity was observed in subcortical structures at 17 hr of ethanol withdrawal. No change in any transcription factor DNA-binding activity was observed in the brain stem. Our results suggest that increased expression of immediate early genes is coupled with an increase in DNA-binding function, indicating that they may play a role in the long-term molecular response to ethanol withdrawal.

Animals↗

PubMed1993

History of circumcision, medical conditions, and sexual activity and risk of penile cancer.

BACKGROUND: Epidemiological evidence suggests lack of neonatal circumcision as the strongest risk factor for penile cancer, but the role of sexually transmitted diseases in the etiology of penile cancer has remained unclear. PURPOSE: To further clarify risk factors for penile cancer, we examined the role of circumcision, personal characteristics and habits (such as smoking), sexually transmitted diseases, past sexual activity, and medical conditions of the penis. METHODS: A population-based, case-control study was conducted in western Washington state and in the province of British Columbia. We interviewed 110 men with penile cancer diagnosed from January 1979 to July 1990 and 355 control subjects from the general population, frequency matched to case subjects on age and date of diagnosis. Tumor tissue from 67 case subjects was tested for human papillomavirus (HPV) DNA by polymerase chain reaction. Results of blood tests from 69 case subjects and 208 control subjects were available for study. STATISTICALLY SIGNIFICANT RESULTS: Relative to men circumcised at birth, the risk for penile cancer was 3.2 times greater among men who were never circumcised and 3.0 times greater among men who were circumcised after the neonatal period. For current smokers, the risk was 2.8 times that of men who never smoked. The risk among men reporting a history of genital warts was 5.9 times that of men reporting no such history. Of 67 tumors tested for HPV DNA, 49% were positive; the majority of these positive tumors (70%) were type 16, which has been associated with anogenital carcinoma. Relative risks (RRs) associated with a reported history of penile rash or penile tear were 9.4 and 3.9, respectively. Among men not circumcised at birth, RRs associated with presence of smegma and difficulty in retracting the foreskin were 2.1 and 3.5, respectively. Twenty-eight percent of case subjects, compared with only 10% of control subjects, reported 30 or more sexual partners, and men with HPV-positive tumors were more likely to report a greater number of sexual partners. CONCLUSIONS: These results suggest that the absence of neonatal circumcision and potential resulting complications are associated with penile cancer. Additionally, medical conditions of the penis, sexual activity, infection with HPV, and smoking may increase the risk for penile cancer. IMPLICATIONS: A larger study would allow examination of interrelationships of circumcision, infection with HPV, and smoking as risk factors.

Aged↗

PubMed1993

Sequence variation in the noncoding region of human papillomavirus type 16 detected by single-strand conformation polymorphism analysis.

Human papillomavirus (HPV) type 16 variants were found by single-strand conformation polymorphism (SSCP) analysis of the noncoding region of the viral genome. Two sets of primers were used to analyze a 1018 bp region spanning nucleotides 7109-222. Twelve SSCP patterns were demonstrated among HPV 16 DNAs purified from 48 anal specimens from 24 homosexual men. Seven patterns were detected among 10 HPV 16 isolates from cervical carcinomas. In two pairs of sex partners, identical variants were recognized in each partner of the pair. Infection with two variants of HPV 16 from 2 specimens was observed in 1 of 21 subjects for whom there were multiple samples over time. DNA sequence analysis of 7 isolates confirmed that the SSCP technique showed polymorphisms only in fragments that had base substitutions and that all of these base substitutions resulted in detectable shifts in fragment mobility.

Anal Canal↗