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Biomedical subjects

J Seed

Publications and source records attributed to J Seed.

At least 19 recordsLinked to original sources
PubMed2001

Harmonization of cancer and noncancer risk assessment: proceedings of a consensus-building workshop.

Significant advancements have been made toward the use of all relevant scientific information in health risk assessments. This principle has been set forth in risk-assessment guidance documents of international agencies including those of the World Health Organization's International Programme on Chemical Safety, the U.S. Environmental Protection Agency, and Health Canada. Improving the scientific basis of risk assessment is a leading strategic goal of the Society of Toxicology. In recent years, there has been a plethora of mechanistic research on modes of chemical toxicity that establishes mechanistic links between noncancer responses to toxic agents and subsequent overt manifestations of toxicity such as cancer. The research suggests that differences in approaches to assessing risk of cancer and noncancer toxicity need to be resolved and a common broad paradigm for dose-response assessments developed for all toxicity endpoints. In November 1999, a workshop entitled "Harmonization of Cancer and Noncancer Risk Assessment" was held to discuss the most critical issues involved in developing a more consistent and unified approach to risk assessment for all endpoints. Invited participants from government, industry, and academia discussed focus questions in the areas of mode of action as the basis for harmonization, common levels of adverse effect across toxicities for use in dose-response assessments, and scaling and uncertainty factors. This report summarizes the results of those discussions. There was broad agreement, albeit not unanimous, that current science supports the development of a harmonized set of principles that guide risk assessments for all toxic endpoints. There was an acceptance among the participants that understanding the mode of action of a chemical is ultimately critical for nondefault risk assessments, that common modes of action for different toxicities can be defined, and that our approach to assessing toxicity should be biologically consistent.

Animals↗
PubMed1995

Male circumcision, sexually transmitted disease, and risk of HIV.

Our objective was to describe associations among male circumcision, behavioral and demographic variables, ulcerative and nonulcerative sexually transmitted disease (STD), and human immunodeficiency virus (HIV) infection via a cross-sectional study in Kigali, the capital of Rwanda. Our subjects were 837 married men who volunteered for HIV testing and counselling. Uncircumcised men had a relatively low-risk profile in that they reported fewer lifetime sexual partners and prostitute contacts than circumcised men and were more likely to live in rural areas with lower HIV prevalence rates. Uncircumcised men were also less likely to report a history of sexually transmitted disease (64% versus 73%, p = 0.01), although they were more likely to report genital ulceration (GUD) (24% versus 17%, p < 0.03) and to have inguinal adenopathy noted on physical exam (42% versus 29%, p = 0.009). Despite the low-risk profile, uncircumcised men had a higher prevalence of HIV infection than circumcised men (29% versus 21% HIV positive, p = 0.02), which was most marked in men reporting five or more lifetime sex partners (36% versus 23% HIV positive, p = 0.005) or contact with prostitutes (35% versus 23% HIV positive, p = 0.009). Circumcision remained a predictor of HIV infection in multivariate analyses (multivariate odds ratio 1.69, 95% confidence interval 1.16-2.47). Lack of circumcision is associated with a higher risk of HIV infection in Rwandan men. Further research is needed to determine whether this higher risk is due in part to poor hygiene or to complex mechanisms operating through the acquisition of other sexually transmitted diseases. Circumcision may be an appropriate risk reduction approach for men with known exposures to the virus when there are constraints to alternatives, such as condom use.

Adult↗
PubMed1995

Chemical mixtures: current risk assessment methodologies and future directions.

Some of the most challenging problems that toxicologists confront are determining how biological effects of components in a complex mixture may interact, determining how these interactions affect the overall toxicity of the mixture, and determining how to incorporate this information into risk assessments of chemical mixtures. There has been considerable effort in this area since the publication of the U.S. Environmental Protection Agency's guidelines for risk assessment of chemical mixtures in 1986. This paper reviews the terminology used to describe chemical interactions and the methodologies that have been developed for conducting risk assessments of chemical mixtures. Particular attention is directed towards an examination of the applicability and validity of the methods for the assessment of risk posed by exposure to environmentally relevant concentrations of chemical mixtures. Limited, yet compelling, data are reviewed that suggest that for noncancer endpoints, adverse effects are unlikely to occur when the individual components in the mixture are present at levels well below their respective thresholds. Synergistic or antagonistic effects, not readily predicted from the mechanisms of action of the individual components, are possible when the mixture components are present at levels equal to or above their individual thresholds. Finally, synergistic carcinogenic effects have been observed in animal studies of mixtures, even at relatively low doses.

Animals↗
PubMed1991

Isolation and partial characterization of a transformation-associated sequence from human nasopharyngeal carcinoma.

A transforming activity associated with Chinese nasopharyngeal carcinoma (NPC) cell line CNE2 DNA has been identified by transfer into nontransformed promotion-sensitive mouse JB6(P+) C141 cells. To clone this transformation-associated sequence, we carried out three cycles of transfection, followed by cloning of anchorage-independent transformants in soft agar. A tertiary CNE/JB6 clonal transfectant cell line 625 whose DNA showed transforming activity, as indicated in both soft-agar assay and nude-mice implantation, was used to make a genomic library in the vector lambda dash. Using the human repeated sequence Blur 8 to screen the library, we obtained 10 human Alu-positive clones. A cloned Alu-positive insert of 16 kbp, CNE 323, was characterized in detail. CNE 323 transferred moderate transforming activity when introduced into JB6 P+ cells and showed no homology to Ha-, Ki-, or N-ras genes; human promotion sensitivity genes; src, myb, jun, myc, fos, raf, or int-2 oncogenes; or epidermal growth factor receptor. The isolated CNE 323 DNA sequence appeared to preserve the genomic structure of the original sequence found in CNE2 cells and in nude mouse tumors induced by CNE2 cells or by CNE/JB6 transfectant cells, indicating that the cloned NPC sequence was activated during NPC carcinogenesis and not during transfection or construction of the library, and that the cloned sequence or a larger sequence of which it was part played a role in tumor formation. Finally, we identified a 1.3-kb mRNA that hybridizes to a subclone of the 16-kb NPC sequence in CNE2 cell poly (A)+ RNA.

Animals↗
PubMed1988

Clonal analysis of vertebrate myogenesis. VIII. Fibroblasts growth factor (FGF)-dependent and FGF-independent muscle colony types during chick wing development.

The effect of bovine fibroblast growth factor (FGF) on the in vitro differentiation of various stage-specific populations of skeletal muscle colony-forming (MCF) cells from the developing chick wing bud was examined. The results show that bovine FGF (3 ng/ml daily) delays the onset of differentiation of MCF cells obtained from Day 4-12 wing buds by about 1 day; but, in addition, the results demonstrate that a subset of colony-forming cells derived from stage 23-27 (Day 4-5) embryos require FGF for myogenic differentiation. The FGF-dependent MCF cells attach and grow in the absence of FGF, but do not differentiate unless given FGF within 1-3 days after inoculation. Thus, between stages 23 and 27 the myogenic population contains discrete subclasses that are FGF dependent and others that are FGF independent. Both subclasses are found within two of the previously classified MCF cell populations, the early and late MCF cells. FGF-dependent and independent early MCF cells are present within the wing bud until stage 25, after which only the FGF-independent early MCF subclass persists. Similarly, both FGF-dependent and -independent late MCF cells are present between stages 25 and 27, but only the FGF-independent late MCF subclass remains after stage 31. The mechanisms responsible for relative changes in the proportions of MCF cell subclasses and for the FGF requirements are not understood. In addition, while FGF is required, there is no evidence suggesting that FGF triggers skeletal muscle terminal differentiation within the FGF-dependent MCF cell subclasses.

Animals↗
PubMed1988

Fibroblast growth factor levels in the whole embryo and limb bud during chick development.

A growth factor with properties very similar to fibroblast growth factor (FGF) was detected in the yolk and white of unfertilized chick eggs, and in the limb bud and bodies of Day 2.5 (stage 18)-13 chick embryos using two complementary and highly sensitive biological assays-competition of 125I-a-FGF binding to the FGF receptors of 3T3 cells and stimulation of DNA synthesis in MM14 cells, a permanent mouse skeletal muscle cell line that is dependent upon FGF for proliferation. Further evidence of the similarity of this growth factor to FGF is provided by the finding that biological activity is lost when the material is bound to a heparin-Sepharose column and restored upon elution with 2.5 M NaCl; the 2.5 M NaCl fraction from Day 12 embryos contains several polypeptides of apparent molecular weights 12,500-17,500. The level of FGF in the embryonic chick body is fairly constant between Days 2.5 and 6 (stages 18-29), ranging between 1 and 2 ng FGF/mg protein; but thereafter the level increases so that by Day 13 the body contains about 15 ng FGF/mg protein. In contrast, the level of FGF in the limb but is higher than that in the rest of the body until Day 5 (stage 27); it then undergoes a transient decrease between Days 6 and 7, after which it increases but remains below the level observed in the remainder of the body.

Animals↗
PubMed1984

Temporal separation of the migration of distinct myogenic precursor populations into the developing chick wing bud.

The developing chick limb bud contains several stage-specific populations of muscle colony-forming (MCF) cells. The cell lineage relationships of these populations are not completely understood, but previous studies have suggested that there may be at least two myogenic precursor populations present in the limb bud. To investigate the heterogeneity of the precursor population, the migration of myogenic precursor cells into the wing anlagen was stopped at various times by grafting stage 15-18 wing buds to the flank or chorioallantoic membrane regions of host embryos. The grafted wings were subsequently assayed for the various MCF cell populations. The data provide further support for the existence of two distinct myogenic precursor populations that migrate into the wing anlagen at different times; precursors to early MCF cells are present by stage 15, whereas precursors to late MCF cells are not present until the end of stage 16. The fact that wing buds which are grafted to a foreign location at stage 15 exhibit exclusive development of early MCF cells suggests that late MCF cells are not direct cell lineage descendants of either the early-type precursors or early MCF cells.

Animals↗
PubMed1982

An evaluation of the host-mediated assay and body fluid analysis. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

The methodologies and status of the Host-Mediated Assay were reviewed using the published literature available up to June 1980. The Working Group reviewed 274 documents, including abstracts, research articles, review articles, and publicly available contracts and grant final reports. From this group, abstracts and reviews were rejected from critical evaluation. 77 documents were accepted and reviewed by the Working Group and the test results summarized. These selected documents yielded 208 chemicals that were evaluated in th host-mediated assay. Of these chemicals, 133 were mutagenic in this assay with one or more indicators. 76 chemicals, several of which are not considered to be carcinogenic, were not detected by any of the indicators. Of the 208 chemicals, 125 had been tested in carcinogenicity assay in rodents. 90, or 71%, of the carcinogens were detected as mutagens in the Host-Mediated Assay. In several cases, those carcinogens not detected may have been negative because of improper selection of the indicator. The Working Group concluded that the Host-Mediated Assay is an important test in mutagenicity/carcinogenicity research and that, by proper selection of protocols and indicators, valuable information can be gained that otherwise would be overlooked strict, in vitro assays.

Animals↗
PubMed1980

Age determination of the fetal and neonatal pigtailed macaque (Macaca nemestrina) from somatometric measurements.

Crown-rump length, foot length and body weight were measured on 134 pigtailed macaque (Macaca nemestrina) fetuses and neonates between 50 and 176 days of gestation. Regression analysis was performed and linear equations generated that described the relation of age to each linear measurement. From the equations, best fit curves (sex-combined for the linear dimensions and sex-specific for weight) were drawn. The three variables were all highly correlated with gestational age, with the standard error of the estimate 1 week or less in each case. On the basis of accuracy of age prediction, reliability and simplicity of measurement, foot length was the best linear measurement for determining age, particularly after 100 gestational days.

Analysis of Variance↗
PubMed1979

Supernumerary epiphyses in the macaque (Macaca nemestrina).

The frequency, age distribution and development of supernumerary epiphyses in the hand and foot were radiographically documented in 98 macaque fetuses and infants. Extra epiphyses were observed only on distal metacarpal 1 and metatarsal 1, and were present in 15% of a cross-sectional sample and 20% of a longitudinal sample. They appeared coincidentally with the ossification of other secondary epiphyses of the hand and foot. Development of extra epiphyses in this species seems to be a normal phenomenon.

Animals↗
PubMed1966

The synthesis of DNA, RNA, and nuclear protein in normal and tumor strain cells. I. Fresh embryo human cells.

Interferometric and photometric measurements have been made on replicating embryo human cell cultures. From a study of the relations between successive physical measurements on individual cells, it was found that the net syntheses of DNA, nuclear RNA, nuclear protein, and cytoplasmic RNA are closely associated during interphase. Additional measurements of DNA and cytoplasmic RNA on freshly prepared replicating monkey kidney cells gave similar results. In auxiliary experiments with embryo human cells, an inhibition of the onset of DNA synthesis (produced by a dose of X-rays) was found to block the majority of the accumulation of nuclear protein and RNA and about half the accumulation of cytoplasmic RNA. These results are consistent with others previously reported in dividing cell cultures freshly prepared from normal tissues.

Cell Division↗
PubMed1966

The synthesis of DNA, RNA, and nuclear protein in normal and tumor strain cells. II. Fresh embryo mouse cells.

Interferometric and photometric measurements have been made on replicating embryo mouse cell cultures. From a study of the relations between successive physical measurements on individual cells, it was found that the net syntheses of DNA, nuclear RNA, nuclear protein, and cytoplasmic RNA are closely associated during interphase. In auxiliary experiments, an inhibition of the onset of DNA synthesis (produced by a dose of X-rays) was found to block the majority of the accumulation of nuclear protein and nuclear RNA. These results are consistent with others previously reported in dividing cell cultures freshly prepared from normal tissues.

Animals↗
PubMed1966

The synthesis of DNA, RNA, and nuclear protein in normal and tumor strain cells. 3. Mouse ascites tumor cells.

Interferometric and photometric measurements have been made on replicating mouse ascites tumor cell cultures. From a study of the relations between successive physical measurements on individual cells, it was found that whereas the net syntheses of nuclear RNA and nuclear protein are closely associated during interphase, they are dissociated from DNA replication to a significant extent. These results agree with others reported in replicating cell strains derived from tumors. In auxiliary experiments an attempt was made to block the initiation of DNA synthesis by X-irradiation: although large amounts of nuclear protein accumulated in some cells in the absence of DNA synthesis, the inability to hold the DNA block for an interphase time prevented a quantitative analysis of the results.

Animals↗
PubMed1966

The synthesis of DNA, RNA, and nuclear protein in normal and tumor strain cells. IV. HeLa tumor strain cells.

Interferometric and photometric measurements have been made on HeLa cells, a strain of cells originally derived from a human carcinoma. From a study of the relations between successive physical measurements on individual cells, it was confirmed that, whereas the net syntheses of nuclear RNA and nuclear protein are closely associated during interphase, they are dissociated from DNA replication to a significant extent. These results on nuclear metabolism agree with others previously reported in cell strains derived from tumors; they contrast with results from freshly prepared normal cells, where the net syntheses of DNA, nuclear RNA, and protein are closely associated during interphase. Cytoplasmic measurements on HeLa cells showed that much of the net synthesis of cytoplasmic RNA is associated with DNA replication as in normal cells, and they failed to detect transfer from the nucleus of a stable RNA component synthesized independently from DNA replication. In auxiliary experiments, an inhibition of the onset of DNA synthesis was produced by a dose of X-rays; under these conditions it was shown that the major part of the accumulation of nuclear protein was independent of DNA replication and that the accumulation of nuclear RNA was equivalent to or slightly less than that of nuclear protein. About half the accumulation of cytoplasmic RNA was inhibited when DNA synthesis was blocked.

Cell Nucleus↗