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Biomedical subjects

S W Jordan

Publications and source records attributed to S W Jordan.

At least 19 recordsLinked to original sources

Cervical papillomavirus infection and cervical dysplasia in Hispanic, Native American, and non-Hispanic white women in New Mexico.

BACKGROUND: Human papillomavirus infections of the cervix are found with varying frequencies in different populations worldwide, and have been associated with cervical cytologic abnormalities. METHODS: We studied 1,603 randomly selected Hispanic, Native American, and non-Hispanic White women in New Mexico to determine the prevalence of cervical HPV infection in these ethnic groups, and its association with Pap smear abnormalities, using a new commercial dot-blot hybridization assay. RESULTS: Nine percent of all women screened had evidence of cervical HPV infection (13.7% of non-Hispanic White women, 9.7% of Hispanics, and 6.6% of Native American women). Prevalence was higher in younger women ages 14-19 years than in older age groups. Over half of women with cervical HPV infection (n = 145) had normal Pap smears. The proportion of infected women increased among those with more advanced cytopathologic abnormalities; 5.6 percent with normal Pap smears had cervical HPV vs 66.7 percent with moderate-severe dysplasia. CONCLUSIONS: Cervical HPV infection is common among New Mexico clinic attendees, varies in prevalence among the three major ethnic groups, and is strongly associated with cervical cytopathologic abnormalities.

Adolescent

Quantitative morphology of late renal radiation injury.

Late radiation injury manifests itself in all morphologic compartments of the kidney, but loss of cell mass is most significant in the proximal convoluted tubules. Development of an end stage or nonfunctional kidney requires 12 or more months after single fraction X ray exposures of about 12 Gy (2, 5, 13) and is associated with marked morphologic alterations of renal tubules. Radiation induced changes were studied at 6 months after irradiation, a time interval when histological alterations appear minor, but in previous studies were shown to correlate with the later end stage alterations (5, 8, 9). Renal alterations were graded objectively based on renal weight, variation in size of tubule cell nuclei, and glomerular nuclear volume fraction. Irradiation was associated with loss of renal weight, increased variability of tubule nuclear size, and previously unappreciated changes in glomerular nuclear volume fraction. A classification index derived from a weighted combination of renal weight ratio and tubule cell nuclear variability correlates with radiation dose and with previously established subjective histologic grading of renal damage, and allows objective comparisons of various fractionation schedules.

Animals

The cytogenetic and hepatotoxic effects of dioxin on mouse liver cells.

The cytogenetic and hepatotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on mouse liver cells were investigated. Male C57BL/6J strain mice, which have TCDD receptors, were given single intraperitoneal injections of 25, 37.5, 75 and 150 micrograms of TCDD/kg body weight or corn oil carrier alone. Two-thirds hepatectomies were carried out at 1 or 7 days after injection and chromosomal aberrations and mitotic indexes of the regenerating hepatocytes were scored 54 hr after hepatectomy. Liver sections from additional intact mice were studied for TCDD-hepatotoxicity at 1, 7 and 30 days after injection. The three high doses of TCDD caused hepatotoxicity with necrosis of liver cells and focal architectural collapse by 30 days after injection. No evidence was obtained of an increase in the frequency of chromosomal structural aberrations at doses that allowed sufficient mitotic activity for cytogenetic evaluation. We conclude that TCDD is not a clastogen for mouse hepatocytes, although high doses cause marked hepatocellular necrosis.

Animals

Video-based image collection for quantitative histopathology.

Obtaining histologic images for computer-based morphometric analysis is associated with a number of standardization problems, which must be solved if reproducible data collection is expected. These problems include tissue processing, sectioning and staining, standardizing and calibrating the video camera and determining the appropriate sampling rate (pixels/micron). Suggested solutions for these problems are presented for a specific image analysis system, but are applicable to other systems with similar capabilities. Biologic variability is not eliminated by computer-assisted analysis, so it is important to minimize data-collection artifacts by parallel processing of experimental and control material, as in other investigative work.

Animals

Hepatotoxic doses of dioxin do not damage mouse bone marrow chromosomes.

We report on a study of the cytogenetic and hepatotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mice of the C57B1/6J (with high-affinity TCDD receptor) or DBA/2J (with low-affinity TCDD receptor) strains were given single intraperitoneal injections of 50, 100 or 150 micrograms of TCDD/kg body weight. At various times (8-48 h) after injection, we examined bone marrow cells for cytogenetic effects by performing structural aberration, sister-chromatid exchange, and micronucleus tests. 1 month after exposure, liver sections were studied for hepatotoxic effects. We found no evidence of chromosome damage by TCDD given in doses that cause liver damage in both strains of mice.

Animals

Fraction size, dose and time dependence of X ray induced late renal injury.

Histologic quantitation of renal radiation injury based on an intact mouse model correlates well with loss of renal mass, as measured by the ratio of right to left renal weight, radiation dose, and time after irradiation. Use of the radiation dose at which 50% of animals show renal tubular changes of a specified grade (ED50), allows comparison of 1, 5 and 15 fraction exposures. The X-ray dose necessary to effect significant injury (Grade 3 change) by six months after irradiation (ED50) was 11.6, 25.7, and 44.0 Gy for single, 5, and 15 fractions, respectively. Isoeffect plots of total radiation dose as a function of fraction number are linear on logarithmic coordinates, indicating that this relationship followed a power function. When plotted as inverse total dose versus dose per fraction, the six month post-irradiation data were linear, but the 12 month data were not. Lack of linearity is not in agreement with the multi-fraction isoeffect linear quadratic model.

Animals

Meningeal carcinomatosis from an ovarian primary: a clinicopathologic study.

Meningeal carcinomatosis due to primary ovarian carcinoma is an uncommon metastasis that presents difficult problems in diagnosis and management of patients known to have this disease. There is evidence that extended survival due to advances in treatment of ovarian carcinoma has improved our ability to diagnose meningeal carcinomatosis of this tumor more often. Herein the first case of meningeal metastasis of primary ovarian cancer with cytologic and postmortem examination is discussed.

Adenocarcinoma

The pathogenesis of radiation injury in complex tissues: an overview of problems and probes.

The evaluation of radiation injury in complex organs has tended to lag behind comparable areas of investigative interest. This observation is somewhat surprising in view of the increased use of radiotherapy as a primary or adjuvant mode of therapy for malignant disease. In part, this problem appears to relate to the difficulty of identifying and quantifying the morphologic consequences of radiation injury in complex organs, in which the various component tissues exhibit a broad spectrum of radiosensitivities. Two approaches have been employed to address this problem: (1) utilization of sophisticated probes to evaluate the functional and morphologic sequelae of radiation injury and (2) segmentation of complex tissues into their component parts, which are then evaluated individually. Both approaches are illustrated in the papers presented in this issue. The purpose of this overview is to call attention to some of the attendant difficulties of the former approach, as seen in an ongoing investigative program concerned with radiation injury of the kidney.

Animals

Computer-assisted morphometric analysis of renal radiation response.

A single x-ray dose of 1,200 to 1,600 rads to the mouse kidney is associated with definite morphologic alteration but minimal functional impairment at six months; this progresses to profound structural and functional impairment by one year after irradiation. Subjective morphologic assessment of renal damage at six months correlates well with total radiation dose, fractionation schedule and energy characteristics of the radiation beam but does not provide adequate quantitative numerical data for sophisticated statistical tests of significance or for comparisons of effect variability at given dose levels. This investigation assessed the applicability of computer-assisted morphometric analysis (CAMA) for quantitation of effects and in making statistical comparisons of significance between kidneys subjectively classified as to degree of histologic alterations. Images of renal cortex tubular nuclei from the various histologic grades were digitized, recorded and analyzed with the CAMA system. Results indicate that the reliability of specific grade assignment by CAMA for individual nuclei was inadequate but that separation of irradiated and unirradiated renal tissue (bivariate group means) was quite distinct and of high reliability. Differences were present among the four irradiated histologic grades, but they were not marked, especially among the three highest grades. More accurate quantitation of nuclear size variations was achieved, and chromatin textural differences were detected that were not apparent to the eye. Computer-assisted morphometric analysis appears to have a valuable application in the quantification and analysis of chronic radiation effects.

Animals

Carcinoma of the cervix in Southwestern American indians: results of a cytologic detection program.

Age-specific detection rates for newly diagnosed in situ and invasive uterine cervical carcinoma were determined in a nine-year cytologic cancer detection program during which 34,700 Southwestern American Indian women and 46,200 medically indigent non-Indian women were screening for cervical cancer. For patients less than 35 years of age, cervical carcino a was found more frequently among Indians and Spanish-American Caucasians than among other Caucasian women. At ages 60 and older, the Indian cervical cancer rate was much higher than that of non-Indians. The detection rate for invasive cervical carcinoma among Indian patients is inversely related to the proportion screened at 30 years of age or older. Although at least 60% of Indian women 20 years old, and older, in the geographic area served by the detection program were screened for cervical cancer during the nine-year period, only 27% of those 50 years or older were screened. The age-related variation in screening percentage, in conjunction with the disproportionately large numbers of younger low-risk women, serves to explain the finding of significant invasive cervical carcinoma in an extensively screened population.

Adolescent

Treatment of tumours with the combination of WR-2721 and cis-dichlorodiammineplatinum (II) or cyclophosphamide.

The ability of WR-2721 [S-2(3-aminopropylamino)ethyl-phosporothioic acid] to selectively protect the host against the toxic effects of multiple doses of cis-dichlorodiammineplatinum [cis-Pt] or cyclophosphamide [CY] has been studied in mice and rats bearing 3 different tumours. Selective protection against cis-Pt induced nephrotoxicity has been demonstrated under all conditions studied, with the extent of protection being inversely related to the size of the cis-Pt dose. For example, pre-treatment with 200 mg/kg of WR-2721 30 min before each weekly dose of 2 mg/kg of cis-Pt allows the administration of this cytotoxic agent for 3 times longer before nephrotoxic injury. In none of these studies was there tumour protection. The same pattern was observed with CY, but quantitation of the extent of marrow protection was not possible for the multiple treatment studies, due to the longer latent period between induced and observed death with this drug. We conclude, therefore, that for both of these drugs, selective protection of the kidney and marrow is not only maintained under conditions of multiple treatment, but actually enhanced due to the need for smaller doses of cytotoxic agents in these protocols.

Amifostine

Comparative late effects of X-rays and negative pimesons on the mouse kidney.

A system is described for comparing various modalities and fractionation schedules of radiation by means of their long-term morphologic effects upon the mouse kidney. The comparison system utilizes a grading scale for histopathologic changes in which a given histologic grade depends upon meeting defined threshold criteria, rather than quantitation of a particular measurement. Renal tubular alterations served as the basis for comparison, since they appeared more reliably defined than glomerular changes. The radiation dose that induced a specific threshold effect in kidneys from 50% of the animals at 6 months was defined as the effective dose-50%, or ED50.ED50 was found for x-rays and negative pimesons administered in 1, 2, or 5 fractions. From these data, the relative biologic effectiveness (RBE) of negative pi-mesons with respect to x-rays was determined for each fractionation schedule.

Animals