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A Gilman

Publications and source records attributed to A Gilman.

At least 19 recordsLinked to original sources
PubMed2004

Circumpolar maternal blood contaminant survey, 1994-1997 organochlorine compounds.

During the past 20 years a number of studies have found neurological and immunological effects in the developing fetus and infants exposed to background or only slightly elevated levels of persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs). To address concerns arising from possible increased human exposure in the Arctic and possible effects of POPs, all circumpolar countries agreed in 1994 to monitoring of specific human tissues for contaminants in the Arctic under the Arctic Monitoring and Assessment Program (AMAP). Mothers in eight circumpolar countries contributed blood samples that were analysed at a single laboratory for 14 PCB congeners (IUPAC No. 28, 52, 99, 105, 118, 128, 138, 153, 156, 170, 180, 183, 187) and 13 organochlorine pesticides (aldrin, beta-hexachlorocyclohexane (beta-HCH), dichlordiphenyltrichloroethane (p,p'-DDT), diphenyldichloroethylene (p,p'-DDE), dieldrin, heptachlorepoxide, hexachlorobenzene (HCB), mirex, and the chlordane derivatives alpha-chlordane, gamma-chlordane, cis-nonachlor, oxychlordane and trans-nonachlor). Inuit mothers from Greenland and Canada have significantly higher levels of oxychlordane, transnonachlor and mirex than mothers from Norway, Sweden, Iceland and Russia. Inuit mothers from Greenland also have significantly higher levels of these contaminants than Inuit mothers from Canada and Alaska. These differences among Inuit groups may represent regional dietary preferences or different contaminant deposition patterns across the Arctic. Levels of PCBs are also elevated among some arctic populations due to their consumption of marine mammals and are in the range where subtle effects on learning and the immune system have been reported. The Russian mothers who consume mainly food imported from southern Russia have elevated levels of DDT, DDE, beta-HCH and a higher proportion of lower chlorinated PCB congeners. This study has allowed an assessment of the variation of contaminants such as PCBs and various organochlorine pesticides (DDT, chlordane, etc.) in human populations around the circumpolar north.

Adult↗
PubMed2002

Evaluation for synergistic suppression of T cell responses to minor histocompatibility antigens by chloroquine in combination with tacrolimus and a rapamycin derivative, SDZ-RAD.

The 4-aminoquinolines, chloroquine and hydroxychloroquine, can suppress chronic graft-versus-host disease (GVHD) following blood and marrow transplantation (BMT) in mice and humans, respectively. We hypothesized that chloroquine in combination with tacrolimus and the rapamycin derivative SDZ-RAD can synergistically suppress T cell responses and antigen-presenting cell (APC) function in vitro. We used the APC-dependent C57BL/6 anti-BALB.B T cell response and APC-independent anti-CD3epsilon antibody-induced response to evaluate the role of synergism between chloroquine and tacrolimus or SDZ-RAD on each component of a T cell response to minor histocompatibility antigens. We found that chloroquine with tacrolimus had a greater synergistic suppression of APC-dependent compared to the APC-independent T cell responses, with a combination index (CIx) for 50% inhibition by mean effect analysis of 0.16 and 0.50, respectively (a lower number indicates greater suppression). By contrast, chloroquine with SDZ-RAD had a similar CIx between the two responsed 0.50 vs0.45) suggesting only T cell suppression. Synergy between chloroquine and SDZ-RAD involved a direct effect on T cell cytokine production, whereas synergism between chloroquine and tacrolimus was due to an effect on both T cells and APCs. We conclude that the renal-sparing 4-aminoquinolines may be used syneristically with immunosuppressive drugs currently used for BMT.

Animals↗
PubMed2002

Iodine fortification is related to increased weight-for-age and birthweight in children in Asia.

Severe iodine deficiency causes stunting and mental retardation in utero, but the relation between mild deficiency and child growth is not well known. The use of iodated salt in relation to anthropometric data was examined from recent survey data. After potential confounding factors had been controlled for, significant associations were seen in Bangladesh, India, Nepal, and Sri Lanka. The use of iodated salt was related to increased weight-for-age and mid-upper-arm circumference, most strongly in the second year of life, mainly affecting soft tissue (thinness). The relation with weight-for-age was greater among children of mothers with lower body mass index. The use of iodated salt was related to birthweight in Sri Lanka and in the Philippines, where iodized oil capsules given during pregnancy had a negative effect when used with high levels of iodine in salt. The associations generally were concentrated in large geographic areas, possibly because of interactions with other environmental factors (e.g., selenium and arsenic). The apparent growth response to iodine may reflect functional effects of mild deficiency, which is widespread, possibly including effects on brain development.

Aging↗
PubMed1999

Human health implications of environmental contaminants in Arctic Canada: a review.

This paper assesses the impact on human health of exposure to current levels of environmental contaminants in the Canadian Arctic, and identifies the data gaps that need to be filled by future human health research and monitoring. The concept of health in indigenous groups of the Arctic includes social, cultural, and spiritual dimensions. The harvesting, sharing and consumption of traditional foods are an integral component to good health among Aboriginal people influencing both physical health and social well-being. Traditional foods are also an economic necessity in many communities. Consequently, the contamination of country food raises problems which go far beyond the usual confines of public health and cannot be resolved by health advisories or food substitutions alone. The primary exposure pathway for the contaminants considered in this paper is through the traditional northern diet. For the Inuit, the OCs of primary concern at this time from the point of view of exposure are chlordane, toxaphene, and PCBs. Exposures are higher in the eastern than in the western region of the North. For Dene/Metis, exposure to OCs is in general below a level of concern. However, estimated intake of chlordane and toxaphene has been found to be elevated for certain groups and is a cause for concern if exposures are elevated on a regular basis. The developing foetus and breast-fed infant are likely to be more sensitive to the effects of OCs and metals than individual adults and are the age groups at greatest risk in the Arctic. Extensive sampling of human tissues in the Canadian north indicate that a significant proportion of Dene, Cree and Inuit had mean maternal hair mercury levels within the 5% risk-range proposed by the WHO for neonatal neurological damage. Based on current levels, lead does not appear to pose a health threat while cadmium is likely only a major risk factor for heavy smokers or consumers of large amounts of organ meats. Consumers of traditional foods are exposed to an approximately seven-fold higher radiation dose than non-consumers of traditional foods due predominantly to the bioaccumulation of natural radionuclides in the food chain. Risk determination for contaminants in country food involves a consideration of the type and amounts of food consumed and the sociocultural, nutritional, economic, and spiritual benefits associated with country foods. Risk management options that minimize the extent to which nutritional and sociocultural aspects of Aboriginal societies are compromised must always be considered.

Adult↗
PubMed1998

Spontaneous and follicular fluid-induced acrosome reaction in sperm samples from in vitro fertilizing and nonfertilizing normozoospermic patients.

PURPOSE: One of the most challenging and intriguing groups of infertile patients is that of normozoospermic men who have repeatedly not achieved fertilization in vitro. These cases probably present a wide range of gamete disorders manifested at different stages of the fertilization process. The occurrence of spontaneous and follicular fluid (FF)-induced acrosome reactions (ARs) in in vitro fertilizing and nonfertilizing specimens from normozoospermic IVF patients was assessed, and the effect of Percoll and cryopreservation on the incidence of ARs was evaluated. METHODS: Semen samples from 62 normozoospermic (15 in vitro nonfertilizing and 47 fertilizing) patients were analyzed. Spermatozoa were double-stained with FITC-conjugated Pissum sativum lectin, to assess their acrosomal status, and propidium iodide, to evaluate their vitality, using flow cytometry analysis. RESULTS: A lower average of AR incidence was observed in the nonfertilizing than in the fertilizing group with all treatments. Both groups exhibited an increase in the proportion of ARs following incubation with FF. This rise was most prominent when Percoll-separated fractions were used (15.8 and 25.6% AR in the nonfertilizing and fertilizing groups, respectively). Thawed cryopreserved and fresh fertilizing samples exhibited similar AR rates. CONCLUSIONS: That normozoospermic recurrently nonfertilizing compared to fertilizing semen samples have a lower capacity to undergo ARs is suggested.

Acrosome↗
PubMed1998

Lifetime health risk assessment from exposure of recreational users to polycyclic aromatic hydrocarbons.

In order to assess the lifetime risk of skin cancer for recreational users from dermal exposure to polycyclic aromatic hydrocarbons (PAHs), sediment samples were collected from beach sites along the St. Marys River near Sault Ste. Marie, Ontario, and in Hamilton Harbor and Toronto Harbor, Ontario, and analyzed for PAHs. Dermal exposure and lifetime skin cancer risk were estimated as follows: Concentrations of 11 PAHs with sufficient or limited evidence of carcinogenicity or mutagenicity were converted to benzo(a)pyrene (BaP) equivalents using toxic equivalency factors (TEFs). Lifetime dermal exposure values were derived based on the BaP equivalents in the silt + clay fraction taken as representative of suspended sediment particulates to which recreational users would be exposed. The lifetime health risk of skin cancer associated with such exposures was above the negligible risk level of 1.0 x 10(-6) at offshore Rytac, Lake George Channel, and Bell Point beaches in the St. Marys River; at Pier 4 Park in Hamilton Harbor; and at Humber Bay, Sunnyside Beach, Cherry Beach, and Water Rats Sailing Club in Toronto Harbor. Risk was negligible inshore at the Rytac and Bell Point beaches and at Squirrel Island and Ojibway Trailer Park along St. Marys River, at Lax Beach in Hamilton Harbor; and at Centre Island in Toronto Harbor. Strategies to reduce risk were developed with these communities; a key recommendation was to take a bath or shower within 24 h after a swim because virtually all the PAHs on the skin would be removed.

Animals↗
PubMed1995

Genetic-algorithm selection of a regulatory structure that directs flux in a simple metabolic model.

A genetic algorithm (GA) is used to optimize parameters for allosteric regulation of enzymes in a model of a metabolic futile cycle, in which two metabolites are interconverted by a pair of irreversible enzymatic reactions. The cycle is regulated by end products of the surrounding pathway. The optimization criterion for the GA is the proper direction of chemical flux in the regulated cycle toward one or the other end product in response to a simple, time-dependent model of biochemical "need" based on externally imposed variation of the end product concentrations. An energetic cost, to be held to a minimum, is also imposed on the operation of the cycle. The best-performing individuals selected by the GA are found to switch rapidly the direction of net flux according to need. In different "environments" (specific time courses of end product concentrations), the GA produces better- or poorer-performing individuals. In some cases "generalists" and "specialists" are produced. The present approach provides, purely as a consequence of formally specifying the task of flux direction, the new result of numerical confirmation, in a simple model, of the intuition that negative feedback and reciprocal regulation are important for good flux direction in arbitrary environments, and gives rise to a diversity of structures, suggestive of the results of biological evolution.

Algorithms↗
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↗
PubMed1994

Benzoxazolamines and benzothiazolamines: potent, enantioselective inhibitors of leukotriene biosynthesis with a novel mechanism of action.

A series of benzoxazolamine and benzothiazolamine analogs that inhibit leukotriene (LT) biosynthesis are described. The initial lead, (S)-N-(benzothiazol-2- yl)phenylalanine ethyl ester (5a), was discovered in a screening program for inhibition of Ca-ionophore-A23187-induced LTB4 release in human polymorphonuclear leukocytes (IC50 0.23 microM). Through structural modification, it was determined that hydrophobic substituents in the 5-position and replacement of the phenyl ring of phenylalanine with a cyclohexyl group greatly enhance potency. Several ester bioisosteres that retain potency and enantiomeric selectivity are described. Lead optimization culminated in (S)-N-[2-cyclohexyl-1-(2-pyridinyl)ethyl]-5-methyl-2-benzoxazolamine+ ++ (43b), IC50 0.001 microM. The compounds described are not inhibitors of 5-lipoxygenase but, rather, act at the level of arachidonic acid release.

Arachidonic Acid↗
PubMed1984

Metastatic carcinoma with an unknown primary.

The patient is a 54-year-old white female who was well until 3 weeks prior to admission when she noted vague right upper quadrant pain exacerbated by meals. She lost 12 lbs over that period of time. She complained as well of posterior scalp, left hip, and back pain on initial presentation. Physical examination at the time of admission to hospital showed a middle-aged female in no acute distress. Her vital signs were normal. There was a 1.5 X 1.5-cm firm, tender nodule over the occiput. There was no peripheral adenopathy. The breasts, lungs, and heart were normal. The liver was 14 cm in span. The remainder of the physical examination including a pelvic examination was unremarkable. On admission, the only abnormal laboratory studies were SGOT 106, SGPT 139, and alkaline phosphatase 190. Her chest X ray, flat plate of the abdomen, and mammograms were all normal.

Adenocarcinoma↗