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Biomedical subjects

W Barnes

Publications and source records attributed to W Barnes.

33 records · Page 2Linked to original sources

Rapid dysplastic transformation of human genital cells by human papillomavirus type 18.

This study delineates differences in biologic activity between human papillomavirus (HPV) types 16 and 18. Human cervical and foreskin epithelial cells were cultured and transfected with recombinant HPV-16 and -18 DNA, resulting in immortalized cell lines. Normal epithelial cells as well as HPV-16 and -18 immortalized cells of both early passages (less than 40 population doublings) and late passages (greater than 180 population doublings) were transplanted in athymic mice. Normal squamous cells formed well-stratified epithelium, while HPV immortalized cells developed either normal-appearing epithelium or typical dysplastic changes. Dysplastic changes were seen in none of the 13 grafts with early-passage HPV-16 cell lines, while 9 of 14 grafts with early-passage HPV-18 cell lines developed dysplasias (P less than 0.0004). These results support previous clinical observations suggesting that HPV-18 may be associated with a more aggressive and rapidly progressive form of cervical neoplasia.

Cell Transformation, Viral↗

Clindamycin effect on glycocalyx production in experimental viridans streptococcal endocarditis.

Abundant glycocalyx production by viridans streptococci in the rabbit model of endocarditis has been associated with delayed antimicrobial sterilization. Enzymatic digestion of the glycocalyx with dextranase enhances antibiotic activity. The effect of clindamycin (30 mg/kg, subcutaneous, three times daily) was studied in rabbits with experimental aortic valve endocarditis caused by high glycocalyx-producing viridans streptococci. Animals receiving clindamycin had smaller vegetations that were sterilized more quickly than did controls or animals receiving penicillin or dextranase alone (P less than .001). Penicillin plus dextranase treatment allowed greater bacterial killing than penicillin alone and did not differ significantly from clindamycin treatment. Electron micrographs revealed markedly less cell-adherent glycocalyx on organisms grown in vitro treated with clindamycin versus penicillin and controls. It is hypothesized that clindamycin inhibits glycocalyx production in vivo, allowing better antimicrobial penetration in the infected cardiac vegetation.

Animals↗

Phase II study of vinblastine in previously treated squamous carcinoma of the cervix. A Gynecologic Oncology Group study.

Thirty-six patients with advanced squamous carcinoma of the uterine cervix recurrent after radiotherapy or surgery or first-line chemotherapy were eligible for a phase II study employing vinblastine in a dose of 9 mg/m2 intravenously every 3 weeks until disease progression or toxicity supervened. Two patients were never treated, leaving 34 patients evaluable for toxicity. One patient was inevaluable for response, leaving 33 evaluable for this parameter. Thirty-two patients had prior radiotherapy and 30 had prior chemotherapy. All patients had Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2. Median age was 46 years. Twenty patients had disease in the pelvis and 13 had extrapelvic metastases. Fourteen patients had grade 3 lesions. A median of three courses (range: 1-12 courses) was administered. Ten patients (29.4%) experienced GOG grade 3 or 4 leukocytopenia and 10 had grade 3 or 4 granulocytopenia. Other toxicity included grade 4 gastrointestinal toxicity and anemia in one patient each and two patients with grade 3 neurotoxicity. Twenty patients (60.6%) had stable disease with therapy and 13 had increasing disease. No responses were observed. Vinblastine in this dose and schedule is inactive in previously treated patients with squamous carcinoma of the cervix.

Adult↗

Effect of pulsed ultrasound versus placebo on muscle soreness perception and muscular performance.

The purpose of this study was to compare the analgesic effect of pulsating ultrasound treatment and placebo on delayed onset of muscle soreness produced by an eccentric exercise bout. In addition, the effect of pulsed ultrasound on muscular performance following an eccentric exercise bout was studied. Eighteen untrained subjects were randomly assigned to: 1) ultrasound (A) [N = 6] over the areas of concentrated muscle soreness, i.e. proximal vastus lateralis and distal vastus medialis; 2) placebo ultrasound (B) [N = 6]; and 3) no therapeutic intervention (C) [N = 6]. Baseline data were recorded for maximum isometric knee extension contraction (MVC), maximum knee extension torque (MT), knee extension work (W), and soreness perception (SP). All values were subsequently reassessed 24 and 48 hours after intense muscular activity. Immediately following the 24 hour reassessment the A group received ultrasound treatment, the B group received placebo ultrasound, while the C group received no treatment. Percent deviation from baseline of SP, MVC, MT and W were significantly less for A than B and C (p less than 0.05) at 48 hours post muscle soreness bout. These data indicate that pulsed ultrasound accelerates restoration of normal muscle performance, and thus is effective in decreasing delayed onset of muscle soreness. The mechanism for decreasing soreness perception in the muscle is unknown, but may be related to decreasing intramuscular pressure and/or decreasing the inflammatory response.

Adult↗

Characterization of normal human exocervical epithelial cells immortalized in vitro by papillomavirus types 16 and 18 DNA.

An in vitro system for studying the interaction between human papillomavirus (HPV) 16 and 18 recombinant DNA and normal human exocervical epithelial cells is described. Eight HPV-immortalized human exocervical epithelial cell lines were established; all the lines contained either integrated HPV16 or 18 sequences and expressed HPV mRNAs. Thus, integration and expression appear to be required for immortalization. Immortalized cells (greater than 200 population doublings to date) divided rapidly (doubling time of 30 to 46 h) and morphologically resembled primary cultures of normal human exocervical epithelial cells. They expressed a keratin pattern consistent with their origin from exocervical epithelium. When cultured at high density or in the presence of serum they terminally differentiated. Sublines resistant to terminal differentiation were selected by growth in serum-supplemented medium. Keratin pattern changes suggest they have some properties in common with cervical squamous carcinoma cells. However, HPV-immortalized cell lines were not tumorgenic in nude mice. Thus, HPV16/18 is not carcinogenic by itself. These cell lines represent an appropriate model for studying factors that regulate HPV gene expression in normal cervical epithelial cells and examining the influence of cocarcinogens on neoplastic progression.

Animals↗

Possible prognostic significance of human papillomavirus type in cervical cancer.

While several different human papillomaviruses (HPV) have been associated with cancer of the cervix, it is yet to be determined if specific HPV types have clinical or prognostic significance. To address this question, 30 cases of invasive carcinoma (squamous carcinoma, adenosquamous carcinoma, and adenocarcinoma) with HPV DNA sequences detectable in the tissue were analyzed. HPV type was determined by Southern blot DNA hybridization. Clinical information was obtained by chart review, and all biopsy and surgical specimens were reviewed microscopically without knowledge of HPV type. HPV 16 was detected in 14 cases, HPV 18 in 6, and HPV 31 in 2. In eight samples there were distinctly different, but as yet uncharacterized, HPV DNAs. Of the factors evaluated, tumor grade was found to have a statistically significant relationship to HPV type. Eighty-three percent of HPV 18-associated tumors were grade 3 tumors (5 of 6) as compared to only 7% of HPV 16-associated tumors (1 of 14) (P = 0.002). Age at diagnosis and nodal status in relation to HPV type exhibited a trend but were not statistically significant. The mean age of the HPV 18 group was 37 years, compared to 49 years for the HPV 16 group. Similarly, among Stage IB cancers, nodal involvement was associated with 60% of HPV 18 cases (3 of 5) as compared with 36% of HPV 16 cases (4 of 11). These observations suggest that HPV 18 may be associated with a more aggressive form of cervical cancer than other HPV types.

Adenocarcinoma↗

Diagnostic accuracy of fever as a measure of postoperative pulmonary complications.

Various prevalence rates have been estimated for pulmonary complications after abdominal surgery, and fever has been thought to be a diagnostic indicator. This study quantifies the diagnostic accuracy of fever as a measure of postoperative pulmonary complications and includes the sensitivity, specificity, and positive and negative predictive values. Assessments using fever and chest x-ray film were determined for 270 patients after elective intra-abdominal surgery in three hospitals with six practicing surgeons in a Southern Ontario city. With use of reliable chest x-ray reports indicating lung pathologic findings as positive for pulmonary complication, the prevalence of a positive finding was 57%. The prevalence of a fever (temperature greater than or equal to 38 degrees C) was 40%. The sensitivity and negative predictive value of fever were slightly below 50%, and the specificity and positive predictive value of fever was 68% and 66% respectively. Fever was an accurate indicator of x-ray evidence of atelectasis in only 56% of the subjects. Therefore, neither the presence nor the absence of fever can assure clinicians of the presence or absence of a postoperative pathologic pulmonary complication such as atelectasis.

Abdomen↗

The significance of paraaortic node status in carcinoma of the cervix and endometrium.

Survival in 115 women with cervical carcinoma and 55 patients with carcinoma of the endometrium was correlated with the status of paraaortic lymph nodes and the clinical stage of disease. The survival probability at 48 months for patients with cervical cancer who had negative paraaortic lymph nodes was 86% for stage IB in comparison to 67% for those with advanced disease (clinical stages II, III, and IV). The difference of 19% between these two groups was not statistically significant nor was there a statistical difference in survival between early and advanced disease groups when paraaortic nodes contained tumor (37 vs 20%). For all stages of cervical cancer, survival was 80% with negative nodes and 20% with positive nodes at 48 months. In patients with endometrial carcinoma and negative paraaortic lymph nodes, projected survival at 48 months was 72% for stage I and 77% for stages II and III. When paraaortic lymph nodes demonstrated metastatic disease, survival uniformly decreased to 27% of patients with stage I cancer and 25% of those with stage II and III disease. For all stages of endometrial cancer, survival was 76% with negative nodes and 26% with positive nodes at 48 months. The presence or absence of metastatic disease in the paraaortic lymph nodes is an important prognostic factor that appears to be more useful in predicting survival than clinical stage of disease in patients with cervical and endometrial cancer.

Adenocarcinoma↗

Signal sequence of alkaline phosphatase of Escherichia coli.

The amino acid sequence of the signal sequence of phoA was determined by DNA sequencing by using the dideoxy chain termination technique (Sanger et al., Proc. Natl. Acad. Sci. U.S.A. 74:5463-5467, 1977). The template used was single-stranded DNA obtained from M13 on f1 phage derivatives carrying phoA, constructed by in vitro recombination. The results confirm the sequence of the first five amino acids determined by Sarthy et al. (J. Bacteriol. 139:932-939, 1979) and extend the sequence in the same reading frame into the amino terminal region of the mature alkaline phosphatase (Bradshaw et al., Proc. Natl. Acad. Sci. U.S.A., 78:3473-3477, 1981). As was predicted (Inouye and Beckwith, Proc. Natl. Acad. Sci. U.S.A. 74:1440-1444, 1977), the signal sequence was highly hydrophobic. The alteration of DNA sequence was identified for a promoter mutation that results in the expression of phoA independent of the positive control gene phoB and in insensitivity to high phosphate.

Alkaline Phosphatase↗

Antibiotic treatment of parturient women colonized with group B streptococci.

A prospective study was conducted among third-trimester parturient women with cervical or urethral colonization with group B streptococci to determine the influence of antibiotic treatment on subsequent colonizations among their infants. Cultures were obtained from dry swabs inoculated directly onto selective blood agar media containing neomycin and naladixic acid. Seventy-four women were found to be colonized among 1,098 cultured (7%). A significant reduction in colonization was noted among mothers treated with ampicillin within three weeks of completion of therapy. This difference was no longer apparent at delivery. There was likewise no difference in the colonization rate of infants in the treatment and no-treatment groups. The data suggest that additional measures must be undertaken to prevent maternal recolonization.

Ampicillin↗

Dislocated jaw.

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Joint Dislocations↗

Determinants of genital human papillomavirus infection in low-income women in Washington, D.C.

OBJECTIVES: To confirm the risk factors for genital human papillomavirus (HPV) infection. GOAL OF THIS STUDY: To investigate risk factors for HPV detection independent of the correlated risk factors for cervical neoplasia, in a high-risk population. STUDY DESIGN: We investigated 404 cytologically normal women attending medical assistance clinics in the Washington, D.C. area. Risk factor information was obtained and a cervicovaginal lavage was collected and used for HPV detection and typing by a PCR-based technique. RESULTS: The point prevalence of HPV was 33.7%. This contrasts with the 17.7% and 44.3% observed in the companion reports published in this issue of the journal. HPV prevalence decreased with age and increased with greater numbers of sexual partners. Moreover, more recent sexual behavior was a better predictor of current HPV detection than lifetime number of sexual partners. Numbers of pregnancies and current pregnancy were positively associated with HPV prevalence and there was an indication that current oral contraceptive users had a higher prevalence of HPV compared to never users. Smoking was not associated with increased HPV prevalence. CONCLUSION: Findings support the sexual route of transmission of HPV and confirm the association of HPV detection with age, suggesting the host's ability to clear infection or the virus' ability to become latent.

Adolescent↗