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Biomedical subjects

K Hooper

Publications and source records attributed to K Hooper.

At least 19 recordsLinked to original sources
PubMed2001

Effect of essential amino acids on mouse embryo viability and ammonium production.

PURPOSE: To examine the effect of essential amino acids concentrations on mouse embryo development. METHODS: Mouse embryos were cultured in medium with different concentrations of essential amino acids and development to the blastocyst stage and viability assessed. Ammonium production resulting from medium breakdown and amino acid metabolism by embryos were also assessed. RESULTS: Reducing the essential amino acid concentration significantly increased blastocyst development and cell numbers. Lowering the essential amino acid concentration decreased ammonium production in the medium. CONCLUSIONS: Culture media for the development of preimplantation embryos should have a reduced essential amino acid concentration to facilitate embryo development.

Amino Acids, Essential↗
PubMed2001

Bcl-2 antisense oligonucleotides enhance the cytotoxicity of chlorambucil in B-cell chronic lymphocytic leukaemia cells.

We have previously shown that the Bcl-2 antisense oligonucleotide ODN 2009 can induce apoptosis in B-cell chronic lymphocytic leukaemia (B-CLL) cells. In this study we evaluated whether ODN 2009 could increase the sensitivity of B-CLL cells to Chlorambucil-induced cell death in vitro in order to establish whether the notion of antisense-mediated chemosensitisation could be applied to B-CLL. Bcl-2 antisense in combination with Chlorambucil resulted in a more marked reduction in Bcl-2 protein expression (p = 0.003), enhanced Bax expression (p < 0.0001) and increased apoptosis when compared to cells incubated with Chlorambucil alone (p = 0.03). This increased in vitro cytotoxicity demonstrates a proof of the concept that a combination of Bcl-2 antisense oligonucleotides with conventional chemotherapeutic drugs may elicit an enhanced therapeutic effect in B-CLL and should therefore be considered for further investigation in the form of a clinical trial.

Aged↗
PubMed2000

The PBDEs: an emerging environmental challenge and another reason for breast-milk monitoring programs.

Levels of the polybrominated diphenyl ethers (PBDEs), a class of widely used flame retardants, appear to be rising rapidly in human tissues, as evidenced by studies of human breast milk. The case of the PBDEs illustrates the value of breast-milk monitoring programs in identifying important emerging pollutants, and highlights why such monitoring programs are needed in the United States. A review of the use, occurrence, and toxicity of PBDEs indicates many parallels between some PBDEs, PCBs, and other polyhalogenated persistent organic pollutants, and suggests that the PBDEs may be a significant environmental challenge in the future.

Animals↗
PubMed1999

Tandem-in-time mass spectrometry method for the sub-parts-per-trillion determination of 2,3,7,8-chlorine-substituted dibenzo-p-dioxins and -furans in high-fat foods.

Limits of quantitation (LOQs) for a quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) method were evaluated through replicate analysis of unfortified peanut oil, shortening, lamb fat, and butter for all 2,3,7,8-chlorine-substituted polychlorodibenzo-p-dioxins (PCDDs) and polychlorodibenzofurans (PCDFs). Ten congeners were measurable in butter (0.27-2.5 pg/g) and nine congeners were measurable in lamb fat (0.09-2.6 pg/g) with good precision. LOQs for high-fat foods were estimated by triplicate analysis of peanut oil fortified at two levels. Accurate and reproducible results were achieved at 0.5 pg/g for most PCDD/Fs (1.0 pg/g for heptachlorodibenzo-p-dioxin and heptachlorodibenzofuran and 2.0 pg/g for octachlorodibenzofuran) and at 0.2 pg/g for 2,3,7,8-tetrachlorodibenzofuran (TCDF) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). QISTMS distinguished between catfish and chicken eggs with elevated TCDD levels from background samples collected from the most regions of the continental United States. QISTMS determined the extent of TCDD contamination in butter, lamb fat, and cottonseed oil collected from rural villages in Kazakhstan. Replicate analysis of catfish and chicken eggs by the QISTMS method produced comparable results to high-resolution mass spectrometry (HRMS). Lower limits of detection will be needed if QISTMS is to fully complement HRMS in the measurement of TCDD levels in food.

Animals↗
PubMed1999

Analysis of breast milk to assess exposure to chlorinated contaminants in Kazakhstan: sources of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposures in an agricultural region of southern Kazakhstan.

High levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; up to 208 pg/g fat) were measured in samples of breast milk collected in 1997 from 64 donors [41 first-time mothers (primiparae)] living on state farms in southern Kazakhstan. TCDD was the major contributor (70%) to the toxic equivalents, matching the congener patterns found in breast milk and serum samples collected in 1994 and 1996 from donors in nearby villages. The highest TCDD levels were found in state farms adjacent to a reservoir (zone A), which receives agricultural runoff from cotton fields. TCDD levels in zone A were significantly higher than levels in a region more distant (zone B; > 10 miles) from the reservoir (zone A: mean 53 pg/g, n = 17; zone B: mean 21 pg/g, n = 24; p = 0.0017). Levels of TCDD in breast milk and animal-derived foodstuffs were 10 times U.S. levels. Body burden and dietary data suggest that exposures to TCDD are chronic, environmental, and long term and may be related to the use of chemicals in cotton agriculture. The data suggest that the most likely source is the use of cotton defoliants contaminated with TCDD, and the most likely pathway for human exposure is via the consumption of contaminated foodstuffs.

Adult↗
PubMed1998

Congener-specific analysis of PCBs in human milk from Kazakhstan.

We have characterized the spectrum of PCB contaminants in human milk samples from 95 women in Kazakhstan using GC/MS congener specific analysis. In these samples, 12 PCBs comprised 83% of total PCB concentration, and were similar to the major PCBs reported in other published human milk studies. By summing concentration levels of 80 PCB congeners in the Kazakhstan samples, a mean total PCB concentration of 368 ng/g fat was obtained. This is lower than levels reported in human milk samples from Western Europe. Six indicator PCBs were summed in Kazakh milk samples; their aggregate value was similar to literature values published for human milk from the former Soviet Union. Using WHO's recent TEF scheme, the mean sum of PCDD/F, coplanar PCB, mono-ortho PCB, and di-ortho PCB TEQ is 42 pg TEQ/g fat.

Benzofurans↗
PubMed1998

Analysis of breast milk to assess exposure to chlorinated contaminants in Kazakstan: high levels of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) in agricultural villages of southern Kazakstan.

To assess levels of chlorinated contaminants in breast milk, we measured organochlorine pesticides, polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) in breast milk samples collected in 1994 according to the World Health Organization protocol from 92 donors that were representative of regional populations in southern Kazakstan. High levels (10-120 pg/g fat) of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic of the PCDD/PCDF congeners, were found in breast milk samples from an agricultural region. TCDD was the major contributor (75%) to the international toxicity equivalents of these samples. The same distinctive PCDD/PCDF congener pattern was found in 15 breast milk samples and 4 serum samples collected in 1996 in a follow-up study, and has now been confirmed by three analytical laboratories.

Adolescent↗
PubMed1997

Analysis of breast milk to assess exposure to chlorinated contaminants in Kazakstan: PCBs and organochlorine pesticides in southern Kazakstan.

Organochlorine pesticides (OC) and polychlorinated biphenyls (PCBs) were measured in samples of breast milk taken from 92 donors representative of regional populations in southern Kazakstan. The World Health Organization protocol for assessing levels of chlorinated contaminants in breast milk was followed. The most prevalent OC residues were beta-hexachlorocyclohexane (beta-HCH), p,p'-DDE, p,p'-DDT, hexachlorobenzene, and alpha-HCH. The measured levels of beta-HCH were among the highest reported in the published literature. Data from Aralsk, near the Aral Sea, indicated continuing DDT exposure. Overall PCB-toxic equivalent levels (22 pg/g fat) were similar to those reported in industrialized European countries. PCBs were highest in Atyrau in the Caspian oilfields.

Adolescent↗
PubMed1995

Workshop on perinatal exposure to dioxin-like compounds. I. Summary.

An international workshop reviewed 20 ongoing or recently completed studies of the effects of perinatal exposures to dioxins, dibenzofurans, and PCBs on the reproductive, endocrine, neurodevelopmental, and immune systems. Many of the observed effects are consistent with these compounds acting as "environmental hormones" or endocrine disrupters. This report summarizes the conclusions and future directions described at the workshop.

Animals↗
PubMed1995

Workshop on perinatal exposure to dioxin-like compounds. VI. Role of biomarkers.

Studies of perinatal exposures to dioxin-like compounds (DLCs), coplanar polycyclic halogenated aromatics whose prototype is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), have employed a variety of outcome measures to investigate effects on the reproductive/developmental, endocrine, immune, and neurobehavioral systems. The effects include infertility, growth retardation, fetal loss, changed sexual differentiation, reduced cognitive/motor function, dermatologic and other ectodermal effects, and decreased immune response. Significant biomarkers have included sperm count; CD4/CD8 ratio; and levels of testosterone, T4, and dopamine. Using specific dioxin or PCB congeners, these and other markers were used to investigate the mechanisms of the observed effects. The DLCs, which include some PCB congeners, are characterized by high-affinity binding to the Ah receptor; most biological effects are thought to be mediated by the ligand-Ah receptor complex. Other PCB congeners have low affinity for the Ah receptor, and operate by non-Ah receptor mechanisms. The biologic activity of a PCB mixture is the sum of the agonist and antagonist activities of the different constituents in the mixture. Animal studies with specific PCB congeners can help to clarify these activities. With similar approaches, biologic markers of effect can be developed and applied in epidemiologic studies to monitor for, and predict, adverse effects in humans.

Animals↗
PubMed1994

Fatty acid composition of low-density lipoprotein influences its susceptibility to autoxidation.

Low-density lipoprotein (LDL) oxidation was studied using copper or the water-soluble initiator azobis(2-amidinopropane) dihydrochloride (ABAP) to catalyze the reaction. These studies were carried out with purified, native LDLs that had a well-defined composition and which contained different concentrations of polyunsaturated fatty acids (PUFA) and alpha-tocopherol. The LDL was obtained from nonhuman primates fed diets enriched in cholesterol and one of four types of fatty acids: saturated (Sat), monounsaturated (Mono), omega-6 (omega-6FA), or omega-3 (omega-3FA) fatty acids. The PUFA concentration of the LDLs depended upon the diet and had the following order: omega-6FA > Sat approximately Mono approximately omega-3FA. Linoleic acid was the predominant PUFA in all of the LDLs. The rates of oxidation were linearly dependent upon the concentration of PUFA. When ABAP was used to initiate oxidation the lag time was linearly related to the amount of alpha-tocopherol. However, with copper catalysis no linear correlation was evident. If the different enrichments were analyzed independently, it was found that copper-catalyzed oxidation of LDLs enriched with omega-6 and omega-3 fatty acids showed a linear correlation between the lag time and the amount of alpha-tocopherol but that LDLs enriched with Sat or Mono fatty acids did not show a correlation. These results demonstrate that the rate of oxidation is dependent upon PUFA concentration and that the ability of alpha-tocopherol to inhibit oxidation depends upon the lipid environment and the mode of initiation.

Amidines↗
PubMed1993

Genetic toxicity of malathion: a review.

Mammalian in vivo and in vitro studies of technical or commercial grade malathion and its metabolite malaoxon show a pattern of induction of chromosome damage, as measured by chromosome aberrations, sister chromatid exchanges, and micronuclei. Experiments with purified (> 99%) malathion gave weak or negative results. In contrast to the cytogenetic effects of technical grade malathion, responses in gene mutation assays were generally negative except for malaoxon, which was positive for mammalian gene mutations in both tested instances. This result also could be a consequence of chromosome level changes, however. Dermal exposure, a common human route, caused cytogenetic damage in test animals at doses near those producing positive results by intraperitoneal injection. Workers who apply technical grade malathion and other pesticides have higher levels of chromosomal damage than unexposed individuals. Because of the inactivity of malathion mixtures in gene mutation assays, malathion has been thought to be of little genotoxic concern. However, the pattern of chromosome damage in animals and mammalian cells in culture (including human) indicates that technical grade malathion and its components have not been adequately studied for genotoxic potential in humans.

Animals↗
PubMed1992

Regulation of priority carcinogens and reproductive or developmental toxicants.

In California, 370 carcinogens and 112 reproductive/developmental toxicants have been identified as a result of the State's Safe Drinking Water and Toxic Enforcement Act of 1986. They include pesticides, solvents, metals, industrial intermediates, environmental mixtures, and reactive agents. Occupational, environmental, and consumer product exposures that involve these agents are regulated under the Act. At levels of concern, businesses must provide warnings for and limit discharges of those chemicals. The lists of chemicals were compiled following systematic review of published data, including technical reports from the U.S. Public Health Service--National Toxicology Program (NTP), and evaluation of recommendations from authoritative bodies such as the International Agency for Research on Cancer (IARC) and the U.S. Environmental Protection Agency (USEPA). Given the large number of chemicals that are carcinogens or reproductive/developmental toxicants, regulatory concerns should focus on those that have high potential for human exposure, e.g., widely distributed or easily absorbed solvents, metals, environmental mixtures, or reactive agents. In this paper, we present a list of 33 potential priority carcinogens and reproductive/developmental toxicants, including alcoholic beverages, asbestos, benzene, chlorinated solvents, formaldehyde, glycol ethers, lead, tobacco smoke, and toluene.

Animals↗
PubMed1992

Prioritizing candidate reproductive/developmental toxicants for evaluation.

To provide a rational method for the timely evaluation of possible reproductive/developmental toxicants, a prioritization scheme was developed by the California Department of Health Services to select chemicals for consideration by the Proposition 65 Scientific Advisory Panel. Initially, four ascertainment methods were used to identify and construct a master list of 164 candidate agents. Using two criteria, the potential for human exposure and the perceived reproductive/developmental hazard as judged by an ad hoc committee of experts, 42 candidates from the master list were identified as priority agents. For practical purposes, the 15 priority agents with the highest rankings will be given the highest priority in the review process. Limitations in the prioritization method used and refinements to be incorporated in an annual update are described.

Algorithms↗
PubMed1991

Comparing alternative approaches to establishing regulatory levels for reproductive toxicants: DBCP as a case study.

This paper compares four alternative approaches for deriving regulatory levels for reproductive toxicants by applying them to the available data on the human spermatotoxicant 1,2-dibromo-3-chloropropane (DBCP). The alternatives examined include the Proposition 65 approach (application of a mandatory 1000-fold uncertainty factor to a no-observed-adverse-effect level [NOAEL]), the Environmental Protection Agency (EPA) approach (application of flexible uncertainty factors to a NOAEL), the Benchmark Dose approach (application of flexible uncertainty factors to a dose associated with a known level of change in a reproductive parameter), and the Quantitative Risk Estimation approach (using low-dose linear extrapolation and a model of the relationship between sperm count and infertility). Applied to DBCP, these approaches do not produce substantially different estimates of allowable exposure levels. However, the approaches do have different data requirements and provide different amounts of information on reproductive hazards to risk managers and the public. Neither the Proposition 65 nor the EPA approach provides information about the extent of health risk remaining at a regulatory level. In contrast, the Benchmark Dose approach can provide estimates of the magnitude of sperm count reduction at a regulatory level, and the Quantitative Risk Estimation approach can provide estimates of exposure-induced infertility.

Animals↗
PubMed1991

Reproductive and developmental toxicity of toluene: a review.

Toluene is a widely used industrial solvent, and humans may also have high exposures to toluene from the deliberate inhalation ("sniffing") of paint reducer, paint thinner, or paint for their narcotic effects. A number of case reports describe neonatal effects that have been attributed to toluene abuse during pregnancy. These effects may include intrauterine growth retardation, premature delivery, congenital malformations, and postnatal developmental retardation. The possibility of exposures to other fetotoxic agents, either as impurities or admixtures in toluene-containing products, or by deliberate or accidental exposures to other chemicals or drugs, cannot be excluded in these cases. The fetotoxic effects of toluene have been demonstrated in controlled studies in animals and are comparable to those observed in humans who have abused toluene-containing products before or during pregnancy. Intrauterine developmental retardation is the most clearly established effect in animals, as evidenced by decreased late fetal weight and retarded skeletal development. There is also limited evidence in rodents for skeletal and kidney abnormalities, as well as some evidence for effects on postnatal physical and possibly neurobehavioral development. Estimated daily exposures from experimental studies in animals are compared to estimated human daily intakes at the occupational permissible exposure level and at the level reported to produce euphoria in humans. Acceptable human intakes under California's Proposition 65 and under U.S. Environmental Protection Agency procedures are discussed.

Abnormalities, Drug-Induced↗
PubMed1991

Human somatic mutation assays as biomarkers of carcinogenesis.

This paper describes four assays that detect somatic gene mutations in humans: the hypoxanthine-guanine phosphoribosyl transferase assay, the glycophorin A assay, the HLA-A assay, and the sickle cell hemoglobin assay. Somatic gene mutation can be considered a biomarker of carcinogenesis, and assays for somatic mutation may assist epidemiologists in studies that attempt to identify factors associated with increased risks of cancer. Practical aspects of the use of these assays are discussed.

Biomarkers↗