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Biomedical subjects

A Lorincz

Publications and source records attributed to A Lorincz.

30 records · Page 2Linked to original sources

Reflex human papillomavirus deoxyribonucleic acid testing in women with abnormal Papanicolaou smears.

OBJECTIVE: The study examined interrelationships between sensitivity and specificity of "reflex human papillomavirus deoxyribonucleic acid testing" from liquid-based cervical cytologic specimens by means of receiver operator characteristics curves. STUDY DESIGN: A cohort study was performed on 265 women evaluated by colposcopy because of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion found on Papanicolaou smear. RESULTS: At a positive threshold of 0.2 pg/ml (1000 copies of human papillomavirus per test), human papillomavirus deoxyribonucleic acid testing detected 86% of women with cervical intraepithelial neoplasia and 93% of women with high-grade cervical intraepithelial neoplasia with a specificity of 30%. Decreasing the sensitivity of the human papillomavirus test to 1 pg/ml (5000 copies of human papillomavirus per test) improved the specificity of a positive result to 44% but decreased the clinical sensitivity to 78% for cervical intraepithelial neoplasia grade 2 or 3. Relationships between sensitivity and specificity were influenced by patient age and referral diagnosis. For example, limiting the analysis to only women with a referral for atypical squamous cells of undetermined significance found on Papanicolaou smear and a positive human papillomavirus test threshold of 0.5 pg/ml produced a sensitivity of 90% for cervical intraepithelial neoplasia grade 2 or 3 and a test specificity of 55%. CONCLUSION: Human papillomavirus deoxyribonucleic acid testing of residual cellular material from liquid cytologic specimens appears to be more appropriate for older women (>30 years old) and women with atypical squamous cells of undetermined significance, as opposed to low-grade squamous intraepithelial lesion, on their Papanicolaou smears.

Adolescent↗

Should cervical cytologic testing be augmented by cervicography or human papillomavirus deoxyribonucleic acid detection?

Criticism of the Papanicolaou smear in the lay press and recent federal legislation regulating cytology laboratories indicate a need to reappraise cervical cancer screening programs. This study directly compares three potential screening tests, used alone or in combination. A total of 1012 women aged 18 to 35 years were screened by cytologic testing, cervicography, and hybridization for human papillomavirus deoxyribonucleic acid, with discrepancies being referred by the last two authors. After findings from the entire lower genital tract were combined, 116 women (11.5%) showed definite clinical abnormalities (either exophytic vulvovaginal condylomas or cervical squamous intraepithelial lesions). Another 72 (7.2%) had positive Southern blot hybridizations without accompanying viral expression, yielding a cumulative frequency for established disease or latent infection of 18.6%. When associated vulvovaginal condylomas are disregarded, final groupings with regard to cervical pathologic classification were: 23 high-grade and 71 low-grade squamous intraepithelial lesions, 164 cases of equivocal atypia (34 of which had detectable human papillomavirus deoxyribonucleic acid), and 754 cases with negative results (38 of which had detectable human papillomavirus deoxyribonucleic acid). Cervical screening tests were compared principally by plotting increasingly liberal recall criteria onto receiver operating characteristic curves (i.e., graphs of true-positive results on the Y axis versus false-positive results on the X axis). Used individually, each screening test was valid, but none was substantially better than the others. No matter how liberal the recall criteria, no single test was able to detect all of the 23 definite precursors in this sample. Applying conventional recall criteria (i.e., high- or low-grade lesion suspected), cytologic testing alone detected 12 high-grade squamous intraepithelial lesions (52.2%), at a cost of having to perform colposcopy in 8.7% of the sample. Combining all three tests and setting the end point as just a high-positive result by at least one test, 19 high-grade squamous intraepithelial lesions (83%) were detected, with a recall of 7%. Optimal test performance (96% sensitivity, 4% recall) would have been attained by recalling all patients with high-grade cytologic results or positive cervicography results, plus any patients with low-grade morphologic atypia in which hybridization detected an oncogenic human papillomavirus type. Our conclusions are as follows: (1) Cytologic detection rates are markedly improved by a second or third test; (2) increased screening costs could be offset by not recalling patients with minor lesions with no apparent potential for progression.

Adolescent↗

Human papillomavirus type 16 immortalized cervical keratinocytes contain transcripts encoding E6, E7, and E2 initiated at the P97 promoter and express high levels of E7.

Human cervical keratinocytes represent the specific host for the genital human papillomaviruses (HPV). Transfection of these cells with the DNA of a number of the oncogenic HPVs including type 16 was recently shown to result in their immortalization but not in malignant transformation. In this report we show that viral transcripts for E6 and E7 in these cells were as abundant as in cancer derived cell lines. However, in contrast to cancer derived cell lines, immortalized cervical keratinocytes contained RNA with the potential to encode a full-length E2 protein. In addition, the levels of the E7 oncoprotein were at least as high as in cancer derived cell lines, suggesting that E2 interruption, observed in cancer derived cell lines, is not causally related to the high level of E7 expression and, therefore, deregulation of the P97 promoter may not be a prerequisite for HPV-16 associated cancer development. Furthermore, we show that E6, E7, and E2 encoding transcripts all originate from the viral promoter, P97. Unlike in cancer derived cell lines, all transcripts terminated at the early poly(A) site.

Blotting, Northern↗

Nonculture methods for diagnosing chlamydial infection in patients with trachoma: a clue to the pathogenesis of the disease?

We studied five different tests for diagnosing conjunctival Chlamydia trachomatis infection in specimens obtained from 100 children with moderate-to-severe trachoma. The tests were Giemsa stain, isolation in cell culture, direct fluorescein-conjugated monoclonal antibody, enzyme immunoassay, and a DNA probe. The Giemsa stain was least sensitive at 29%. The other tests gave essentially equivalent performances: sensitivity ranged from 73% to 84% and specificity from 93% to 100%. Seven of the 45 positive specimens were only positive in cell culture, whereas 11 of the 45 were negative in culture but positive in at least two nonculture tests. We speculate that these discordant results actually reflect the biologic status of the chlamydial infection. There appears to be a stage in the infection where chlamydial antigens and nucleic acids can be detected in the absence of infectivity. This stage of infection may contribute to the pathogenesis of trachoma by providing a source of sensitizing antigen.

Azure Stains↗

Localized mycosis fungoides not manifesting as Woringer-Kolopp disease.

A 68-year-old man had a solitary, eczematiform lesion of two years' duration on the digital dorsal surface of his right foot. Despite its innocuous appearance, the lesion showed histologic characteristics of advanced, plaque-type mycosis fungoides. The patient's clinically benign yet histologically malignant disease manifestation is discussed. The distinction between localized mycosis fungoides and Woringer-Kolopp disease is also reviewed.

Aged↗

Regulation of cell size in the yeast Saccharomyces cerevisiae.

For cells of the yeast Saccharomyces cerevisiae, the size at initiation of budding is proportional to growth rate for rates from 0.33 to 0.23 h-1. At growth rates lower than 0.23 h-1, cells displayed a minimum cell size at bud initiation independent of growth rate. Regardless of growth rate, cells displayed an increase in volume each time budding was initiated. When abnormally small cells, produced by starvation for nitrogen, were placed in fresh medium containing nitrogen but with different carbon sources, they did not initiate budding until they had grown to the critical size characteristic of that medium. Moreover, when cells were shifted from a medium supporting a low growth rate and small size at bud initiation to a medium supporting a higher growth rate and larger size at bud initiation, there was a transient accumulation of cells within G1. These results suggest that yeast cells are able to initiate cell division at different cell sizes and that regulation of cell size occurs within G1.

Ammonium Sulfate↗

Lichen planus: an ultrastructural study.

Ultrastructural features of skin lesions are described in 11 patients with lichen planus. Keratinocytes and melanocytes in the basal layer show loss of nuclear membrane, disappearance of nucleoli, homogenization of nuclear material, and aggregation of tonofilaments around the nucleus to resemble cells in the late prophase of the mitotic cycle except that there is no clumping of chromosomes. These cells undergo fibrillar transformation to form densely packed fibrillar bodies (colloid bodies) which are the size and shape of normal cells and frequently have cytoplasmic organelles. Ten per cent of the mainly lympho-histiocytic cells in the dermal infiltrate show changes such as multiple cell membrane discontinuities, disintegration of cytoplasm, and breaks in the nuclear membrane with spilling of nuclear substance either into the cytoplasm or the extracellular space. The shape, size and occasional fibrillar changes in the nuclei and cytoplasm of these cells resemble colloid bodies. Contact sites frequently occurred between cells in the dermal infiltrate, especially between lymphocytes and macrophages. It appears that primary injury to the basal layer cells occurs during the early phase of the mitotic cycle and antigen from this primary site may evoke a cell-mediated type of hypersensitivity reaction. Colloid bodies evolve from cells which have injured nuclei and undergo fibrillar transformation. Dermal as well as epidermal cells may contribute to colloid body formation.

Cell Nucleolus↗

Independent component analysis of temporal sequences subject to constraints by lateral geniculate nucleus inputs yields all the three major cell types of the primary visual cortex.

Information maximization has long been suggested as the underlying coding strategy of the primary visual cortex (V1). Grouping image sequences into blocks has been shown by others to improve agreement between experiments and theory. We have studied the effect of temporal convolution on the formation of spatiotemporal filters--that is, the analogues of receptive fields--since this temporal feature is characteristic to the response function of lagged and non-lagged cells of the lateral geniculate nucleus. Concatenated input sequences were used to learn the linear transformation that maximizes the information transfer. Learning was accomplished by means of principal component analysis and independent component analysis. Properties of the emerging spatiotemporal filters closely resemble the three major types of V1 cells: simple cells with separable receptive field, simple cells with non-separable receptive field, and complex cells.

Action Potentials↗

Molecular variants of human papillomavirus type 16 and risk for cervical neoplasia in South Africa.

Non-European variants of human papillomavirus (HPV) type 16 are generally associated with a greater risk of cervical neoplasia than European prototype variants. We investigated whether this association would persist in a population in which non-European HPV 16 variants were more common. We sequenced HPV 16 isolates in cervical samples collected from 93 Black South African women enrolled in a cervical cancer screening study and examined associations between cervical neoplasia identified though colposcopy with cervical biopsy and the specific HPV 16 variant identified. The European prototype variant (EP) was the most commonly identified variant in this population (47% of all isolates), but African variants (Af-1 and Af-2) were also quite common (41% of all isolates). In contrast to previous studies, we found no evidence that non-European variants were associated with an increased risk of neoplasia. Rather, most of the HPV 16-associated cancers were found in association with EP (71% of 14 cases). In this setting where African HPV 16 variants were common, no increased risk for cervical neoplasia was found among women with these variants compared with other HPV 16 variants.

Adult↗