PubMed Health⌕ Search

Biomedical subjects

J Gandy

Publications and source records attributed to J Gandy.

At least 19 recordsLinked to original sources

Evaluation of immune parameters in propanil-exposed farm families.

The rice herbicide propanil induces alterations in the mouse immune system, causing significant decreases in T cell-dependent and T cell-independent antibody responses. This postemergent herbicide is used extensively in rice production in the Mississippi River delta region of the southern United States. The aerial application and airborne drift of propanil may pose health concerns to exposed farm families living adjacent to sprayed rice fields. To determine if aerial spraying of propanil increases risks of altered immune responses in families bordering rice fields, immune parameters were assessed during a 2-year study. Families living within 100 yards of rice fields were compared in a case control study to farm families whose homes exceeded 1 mile from any rice field. Blood was analyzed in adults (n = 56) and children (n = 52) at three time intervals: (1) preseason, prior to propanil application; (2) 5-7 days after aerial application of propanil to rice fields; and (3) postseason, following harvest. Exposed adults and children were compared with controls for a number of immune parameters. Total cell count and the percentage of various lymphocytes (T cells, B cells, CD4+ helper cells, and CD8+ suppressor cells) and natural killer (NK) cells, mitogen-induced cell proliferation, cytokine (IL-2+) production, and NK cell function were assessed. A comparison of immune function between exposed and nonexposed farm families showed no significant differences, possibly related to propanil exposure. However, some immune test parameters changed as a function of season rather than propanil exposure. The data indicate that individuals living next to rice fields are not at increased risk of altered immune function due to propanil exposure.

Adolescent↗

Propanil (3,4-dichloropropionanilide) particulate concentrations within and near the residences of families living adjacent to aerially sprayed rice fields.

Propanil is widely used as a postemergence herbicide in rice. Because it is typically applied aerially, there is a potential for propanil to drift into and around homes of those living adjacent to rice fields. Propanil has been shown to be immunotoxic in rodent models. The objective of this study was to measure the levels of propanil to which families living adjacent to aerially sprayed rice fields may be exposed. Air levels were sampled by actively and passively collecting propanil in and around the homes of volunteer families living in close proximity to rice fields sprayed with propanil. Homes ranged from 73 m to 113 m from treated rice fields. Sampling was conducted in the home, adjacent to the home (within 5 m of the home), 30 m from the home, and at the edge of the rice field. Concentrations were determined via gas chromatography/mass spectroscopy. Propanil levels adjacent to the homes ranged from nondetectable to 1,106.4 microg per 400 cm2 collection surface (2.0 microg detection limit). Wind direction and wind velocity were the primary determinants of propanil drift. At sites where the prevailing wind was blowing away from the home, no propanil was detected except at the edge of the field. Distance from the edge of the rice field also influenced the amount of drift with higher levels measured at 30 m from the house than adjacent to the house. No propanil vapor was detected on absorbent media sampled in and around the homes. The results indicate that individuals living adjacent to rice fields aerially sprayed with propanil are potentially exposed to variable amounts of propanil, and wind speed and direction are the most important factors that influence the concentration of aerially applied pesticide.

Agriculture↗

Perkinsus marinus tissue distribution and seasonal variation in oysters Crassostrea virginica from Florida, Virginia and New York.

Perkinsus marinus infection intensity was measured in eastern oysters Crassostrea virginica collected in October and December 1993, and March, May, and July 1994 from 3 U.S. sites: Apalachicola Bay (FL), Chesapeake Bay (VA), and Oyster Bay (NY). Gill, mantle, digestive gland, adductor muscle, hemolymph, and remaining tissue (including gonadal material and rectum) were dissected from 20 oysters from each site at each collection time. Samples were separately diagnosed for P. marinus infections by incubation in Ray's Fluid Thioglycollate Medium (RFTM) and subsequent microscopic quantification of purified enlarged hypnospores. At all sampling times and sites, average P. marinus infection intensity (g wet wt tissue-1 or ml hemolymph-1) was lowest in hemolymph samples, and generally highest in the digestive gland. Perkinsus marinus prevalence was 100% at both FL and NY sites for each of the 5 collection times, and, for the VA site, was less than 100% in only 1 month (May 1994). Seasonal intensity patterns and mean total body burdens differed among the sites. Average body burden was highest in VA during October and progressively declined to a minimum in May. This decline was probably due to mortality of heavily infected oysters and diminution of parasite activity associated with colder temperatures and reduced salinities. Intensities varied little during the months of October and December at both the FL and NY sites. Minimum average intensities were observed in March in FL oysters and May in NY oysters. Relatively high P. marinus infection levels that persisted throughout the winter in NY oysters compared with VA oysters could reflect constant high salinity in Long Island Sound which favors parasite activity, and also rapid decline in temperature in the fall that may have prevented epizootic oyster mortalities.

Analysis of Variance↗

Endocrine mechanisms underlying reproductive toxicity in the developing rat chronically exposed to dietary lead.

A dose-response study was conducted in a rat model to examine the effects of lifetime lead exposure on the development of the reproductive system and the endocrine mechanisms underlying these effects. Time-impregnated female Sprague-Dawley rats (n = 10-15/group) were exposed to lead acetate in the drinking water at levels of 0.05%, 0. 15%, or 0.45% (w/v) initiated on gestational day 5. At birth, litters were culled to four male and four female pups. Exposure of dams to lead was continued until weaning, following which, the pups continued to be exposed to lead acetate in drinking water until sacrifice. One male and one female pup from each litter were sacrificed at age 21, 35, 55, and 85 d. A significant dose-responsive decrease in birth weight and crown-to-rump length was observed in all lead-exposed litters. However, no marked effects were observed on anogenital distance/crown-to-rump length ratios. Lead exposure resulted in a delay in sexual maturity as measured by prostate weight in male pups and time of vaginal opening in female pups, which increased with lead dose. These disruptions in reproductive physiology were accompanied by a significant decrease in neonatal sex steroid levels and suppression of the plasma concentrations of testosterone (male) and estradiol (female) during puberty. In male pups, this was accompanied by a significant decrease in plasma luteinizing hormone (LH), elevated pituitary LH content, and a decrease in plasma testosterone/LH ratios at the highest dose. In female pups, although no effects were observed on plasma LH concentration, a similar significant elevation in pituitary LH content was observed during early puberty. Postpuberty, plasma LH and sex steroid concentrations were unaffected at any dose in spite of continued lead exposure. No significant effects were observed on epididymal sperm count in male pups at 85 d of age. In female pups, estrus cycling was only significantly disrupted at the highest lead dose. These data suggest that the reproductive axis is particularly sensitive to lead during specific developmental periods, resulting in delayed sexual maturation produced by suppression by sex steroid biosynthesis. The mechanisms underlying this appear to involve lead actions on both LH release and gonadal function. At low, environmentally relevant blood lead concentrations, adaptation to the continuous presence of the metal ion occurs and surprisingly little effect is observed on adult reproductive endocrinology and physiology.

Administration, Oral↗

Risks of intravenous amiodarone in neonates.

The courses of two neonates treated with intravenous amiodarone for supraventricular tachyarrhythmia, both of whom developed significant adverse effects, are reported. A 13-day-old term newborn developed hypothyroidism after 27 days of mostly intravenous amiodarone for atrioventricular reciprocating tachycardia and severe heart failure. A one-day-old, 36 weeks' gestation newborn developed electromechanical dissociation after receiving an intravenous bolus of amiodarone for rapid atrial flutter. Judicious use of amiodarone is recommended.

Age Factors↗

Neonatal Meckel's diverticular inflammation with perforation.

Meckel's diverticulum occurs in approximately 2% of the general population and is usually asymptomatic. Four percent of cases will present as an acute abdomen caused by intestinal obstruction, gastrointestinal bleeding, and inflammation. A neonatal presentation of Meckel's diverticulum mimicking necrotizing enterocolitis is described.

Enterocolitis, Pseudomembranous↗

Effects of caloric restriction on expression of testicular cytochrome P450 enzymes associated with the metabolic activation of carcinogens.

Previous work demonstrated that microsomal cytochrome P4502A1 (CYP2A1) is expressed in rat testicular Leydig cells. The present study investigates the effects of diet, age, and strain on rat testicular CYP2A1 expression and assesses the potential role of testicular CYP2A1 in the metabolic activation of carcinogens. In ad libitum-fed 18-week-old Fischer 344 rats, testicular CYP2A1 immunoreactive protein and testosterone 7alpha-hydroxylase activity (7alpha-TOHase) exhibited a circadian variation with a daytime maximum and a night-time minimum (82.2 +/- 42.0 and 21.9 +/- 4.5 pmol 7alpha-hydroxytestosterone/min/mg protein, respectively). Caloric restriction (to 60% of ad libitum consumption), which reduces the severity of Leydig cell tumors in rats, decreased expression of both CYP2A1 and testicular 7alpha-TOHase >80% and eliminated their circadian variation. Conversely, caloric restriction induced a circadian rhythm in testicular 7-benzyloxyresorufin-O-dealkylase activity. Testicular microsomes from ad libitum-fed rats having peak diurnal 7alpha-TOHase activity had significantly greater (30%) microsome-mediated aflatoxin B1-DNA binding activity compared to microsomes prepared from nocturnal phase ad libitum-fed or calorically restricted rats which expressed low 7alpha-TOHase activity. In 12-month-old Fischer 344 rats, high CYP2A1 expression was correlated with severe Leydig cell hyperplasia (r = 0.80), whereas CYP2A immunoreactive protein and 7alpha-TOHase were expressed at lower levels in Sprague-Dawley than in Fischer 344 rats and were undetectable in pig, monkey, and human testes. These are strains/species that do not exhibit significant Leydig cell hyperplasia. This suggests that caloric intake, strain, and circadian factors may all mediate testicular CYP2A1 expression in the rat and that CYP2A1 may in turn influence carcinogen activation and pathological status in the testis.

Aflatoxin B1↗

Differential expression of glutathione S-transferase isoforms in compartments of the testis and segments of the epididymis of the rat.

Specific cell types of the mammalian testes demonstrate varying susceptibility to toxic insult by chemical agents. The mammalian testis is divided into two major compartments: seminiferous tubules, the site of spermatogenesis, and interstitium, which contains the Leydig cells. Glutathione S-transferase (GST) expression was examined in isolated compartments of the rat testis and in segments of the epididymis. Western blot analysis revealed the presence of GST class alpha, mu, and pi bands in each of the isolated compartments of the testis, and HPLC analysis of monomeric isoforms provided evidence for differential expression of multiple GST isoforms in testicular compartments. All major isoforms (e.g., forms 1, 2, 3, 4, 6, 7, 8, 9, and 11) were detected in the cytosol of whole testis. Isoform subunit 4 was the major form in the tubule, whereas isoform subunit 11 is the dominant form in the Leydig cells. Isoform subunits 3, 4, and 6 were enriched in the tubules as compared to interstitial or Leydig cells. The preferential action of reproductive toxicants at specific stages of aging may be due to an age-dependent expression of the activating or detoxifying enzymes in the reproductive tract. Therefore, the age-dependent expression of testicular GST isoforms was also examined. Expression of isoform subunits 2 and 4 displayed an age dependence, with the largest increase in these subunits occurring between ages 4 and 15 weeks. Isoform expression did not correlate with serum testosterone levels. HPLC analysis of the GST isoforms in the longitudinal segments of the epididymis and vas deferens revealed differential expression within these segments. Total GST protein and catalytic activity was highest in the caput epididymis and progressively decreased toward the vas deferens. Isoform subunit 2 was the major form expressed in the epididymis. The results of this study indicate that the GSTs are differentially expressed in testicular compartments and epididymal segments, and that this may contribute to susceptibility of different cell types to xenobiotic damage.

Animals↗

Changes in primary and secondary lymphoid organ T-cell subpopulations resulting from acute in vivo exposure to propanil.

Acute exposure to the herbicide propanil is immunotoxic for selected immune functions, as well as causing changes in the weights of the thymus and spleen. Although spleen cellularity and weight increase with propanil exposure, the thymus: body weight ratio decreases with increasing doses of propanil. The present study analyzes the thymocyte subpopulations in the thymus, spleen, and mesenteric lymph nodes. C57Bl/6 mice were treated with either 0, 100, 150, or 200 mg/kg propanil, and 7 d later thymocyte populations were analyzed by flow cytometry. In the thymus, propanil exposure resulted in a dose-dependent decrease in total numbers of T cells, as would be expected with its reduced weight. Determination of the thymocyte subpopulation distribution in the thymus showed a significant reduction in the number of CD3+CD4+CD8- (CD3+4+8-), CD3+CD4-CD8+ (CD3+4-8+), and CD3+CD4+CD8+ (CD3+4+8+) cells. Percent distribution of these thymic cell subpopulations showed similar decreases only with the highest dose. Apparent dose-related decreases in the numbers of CD3-CD4+CD8+ (CD3-4+8+) cells were also noted and were attributed to the general decrease in total thymus cells. The percentage of CD3- subpopulations showed an increasing trend with dose, which suggests that at 7 d postpropanil exposure there may be a specific effect on this most immature population. Although the size and cellularity of the spleen were increased, no change in CD4+ or CD8+ cell distribution was observed. Similarly, mesenteric lymph nodes showed no changes in the cell subpopulation distribution between propanil-treated and control animals.

Analysis of Variance↗

X-ray evidence that in contracting live frog muscles there exist two distinct populations of myosin heads.

Using synchrotron radiation and whole muscles, 2 ms time-resolved x-ray diffraction patterns were recorded at 8 degrees C. The results show that in both isotonic and isometric contractions, as well as in length changes imposed at maximum tension [Po], the meridional third myosin layer line consists of two distinct reflections with different intensities and spacings that measure approximately 14,623 and 14,412 nm at Po. Although the intensity behavior of the two reflections is strikingly different during quick releases, it is very similar during stretches. Study of the time courses indicates that myosin heads diffracting at Po with the approximately 14.623 nm periodicity are actively involved in tension production. Those diffracting at Po with the periodicity of approximately 14.412 nm appear not be associated with tension production during isometric contraction and releases, but the results suggest that they are recruited during stretches and here contribute to tension production. Our most important conclusion is that under all conditions of contraction we have investigated there exist two populations of myosin heads, each with a well defined axial disposition and configuration.

Animals↗

Selective myelotoxicity of propanil.

Propanil, a commonly used herbicide, has been previously shown to be immunotoxic for selected immune functions as well as specific cell types, such as the macrophage. Propanil has also been shown to cause a methemoglobulinemia and anemia through direct action on the erythrocyte. Demonstrated toxicity to both macrophages and erythrocytes raised concern for the possible myelotoxicity of propanil which could contribute to the observed effects of exposure. Therefore, the effect of propanil on several stem and progenitor cell types was assessed 7 days after acute propanil exposure. The results described herein show that propanil, at doses of 50-200 mg/kg body wt, resulted in reduction in the number of myeloid stem cells and early myeloid and erythroid progenitor cells. No reduction in the numbers of more differentiated myeloid and erythroid progenitor cells was noted at even the highest dose used (200 mg/kg). In addition, no statistically significant difference in number of leukocytes per femur was noted. These data suggest that propanil is myelotoxic to early hemapoietic stem cells, but that this reduction is apparently compensated by proliferation of more differentiated progenitor cells for the myeloid and erythroid lineages. It remains unknown whether chronic exposure leads to progressive depletion of additional myeloid and erythroid cells.

Animals↗

Enhanced glutathione S-transferase 7-7 expression in rat hepatic cytosol following treatment with pyrrole.

Rat hepatic GST 7-7 expression in cytosol and in the S-hexylglutathione-agarose affinity purified fraction of cytosol from saline- (control) and pyrrole-treated animals was examined using metabolic activity, SDS-PAGE, immunoblot, and HPLC analyses. Metabolic activity of hepatic cytosol from pyrrole-treated animals was assayed using the substrates 1-chloro-2,4-dinitrobenzene, ethacrynic acid, and acrolein, and an approximately 1.5-, 1.2-, and 1.3-fold increase, respectively, was monitored in the rate of GST-catalyzed substrate conjugation to reduced glutathione. SDS-PAGE and immunoblot analysis using Class Pi GST-specific IgG confirmed that the GST 7 subunit was expressed in hepatic cytosol and in the affinity purified fractions from pyrrole-treated rats. In contrast, the GST 7 subunit was below the limit of detection in hepatic cytosol of saline-treated animals. HPLC analysis demonstrated the presence of the GST 7 subunit in the affinity purified fraction from pyrrole-treated rat hepatic tissue and showed that the level of this subunit was increased approximately 8-fold relative to the barely detectable level present in control tissue. N-terminal amino acid sequencing analysis confirmed the identity of the HPLC peak as GST 7-7. GST subunits 3, 1a, and 1b were elevated approximately 1.7-, 2.0-, and 2.4-fold respectively, in response to pyrrole treatment. These data provide evidence that pyrrole treatment results in de novo expression of GST 7-7 in rat hepatic tissue and suggest that pyrrole-containing compounds potentially generated during disease and/or altered heme metabolism, or those ingested in food products, may alter GST expression in hepatic tissue.

Animals↗

Alteration of macrophage cytotoxicity through endogenous interferon and tumor necrosis factor alpha induction by propanil.

The effect of propanil on mouse peritoneal macrophages (m phi) was measured by determining cytotoxicity via the P815 cell line, which is resistant to tumor necrosis factor alpha (TNF-alpha). Although control animals showed a typical pattern of requiring both interferon (IFN)-gamma and lipopolysaccharide (LPS) for m phi activation, m phi from propanil-treated animals were cytotoxic when induced with LPS alone. This suggested that propanil influenced endogenous IFN levels. This was confirmed by the abrogation of cytotoxicity upon addition of anti-IFN to the cultures. When cells were assayed for IFN transcript, mRNA in resident m phi was present in higher concentrations in propanil-treated animals. IFN mRNA was present in even higher concentrations in m phi from propanil-treated animals after 30 min of culture with LPS, whereas control m phi required 4 hr in culture with LPS to produce similar levels. IFN protein levels were also higher in propanil-treated m phi after culture in the presence of LPS. Thus, propanil induces increased levels of endogenous IFN which probably works in conjunction with LPS to induce P815 cytotoxicity. Because of the known influence IFN has on the increased secretion of TNF-alpha, we tested the tumoricidal activity of m phi from propanil-treated animals against TNF-alpha-sensitive cell lines. When using WEHI-164 or L929 cells, m phi from propanil-treated animals revealed tumoricidal activity with just the addition of LPS or IFN-gamma. This implies that the additional endogenous levels of IFN, combined with other propanil-induced effects, caused increased secretion of TNF-alpha from m phi.

Animals↗

Effects of reproductive tract glutathione enhancement and depletion on ethyl methanesulfonate-induced dominant lethal mutations in Sprague-Dawley rats.

The effects of altering glutathione (GSH) levels in the male reproductive tract have been studied in an attempt to establish a link between chemical-induced perturbations in glutathione and susceptibility of spermatozoa to chemical insult. Tissue GSH levels were enhanced by a treatment regimen of N-acetylcysteine (NAC) (250 mg/kg, 4 treatments at 2 h intervals). With this treatment, GSH levels in liver, testis, caput epididymis, and cauda epididymis were elevated to 126%, 110%, 178%, and 136% of control values. Sexually mature male rats were then treated with NAC and challenged with a dose of EMS (100 mg/kg) to determine if enhanced tissue GSH would protect against EMS-induced dominant lethal mutations. Pretreatment with NAC significantly decreased the post-implantation loss from 7.05 +/- 0.57 with EMS alone to 5.28 +/- 0.47. Conversely, a dominant lethal assay was conducted using different doses of phorone pretreatment to determine the relative contribution of hepatic versus reproductive tract GSH in protecting against EMS-induced dominant lethal resorptions. Doses of 100 mg/kg and 250 mg/kg phorone significantly lowered both hepatic and reproductive tract GSH while 25 mg/kg lowered only hepatic GSH. These three dose levels were used as pretreatments in a dominant lethal study followed by a challenge administration of EMS (50 mg/kg), which is a threshold dose of EMS for producing dominant lethal mutations. Comparison against controls demonstrated a significant potentiation of fetal resorptions in all groups receiving phorone pretreatment, including the 25 mg/kg pretreatment group which only lowered hepatic GSH prior to EMS challenge. The results of these experiments indicate that GSH reserves in the male reproductive tract are insufficient to protect developing spermatozoa from damage by alkylating agents in the absence of hepatic GSH.

Acetylcysteine↗

Comparison of the immunotoxicity of propanil and its metabolite, 3,4-dichloroaniline, in C57Bl/6 mice.

Propanil (3,4-dichloropropionaniline), used extensively as a postemergence herbicide in rice and wheat, has as its major metabolite, 3,4-dichloroaniline (DCA). Propanil has previously been shown to affect the T cell-dependent antibody response. To determine the immunotoxicity of DCA, as well as extend the previous immunotoxicity studies, several T cell-dependent and -independent immune responses were determined after DCA or propanil exposure. Unlike propanil, DCA caused a significant reduction in T-dependent antibody production (anti-SRBC response) only at a high dose (150 mg/kg). DCA or propanil at 150 or 200 mg/kg, respectively, caused a significant reduction in the number of anti-DNP antibody producing cells. However, doses of 37 or 50 mg/kg of DCA or propanil, respectively, caused an increase in the number of anti-DNP antibody producing cells. These data indicate that both propanil and DCA have a differential effect on the T-independent antibody response depending on the dose. Similar to propanil, DCA (at 150 mg/kg) caused a significant increase in spleen weight and cellularity. The effect of DCA or propanil on selected cellular immune functions was also determined. DCA caused a significant decrease in the natural killer (NK) cell activity at doses of 75 or 150 mg/kg, and propanil caused a significant decrease at 100 or 200 mg/kg. Cytotoxic T lymphocyte activity, however, was unaffected even at 150 or 200 mg/kg DCA or propanil, respectively. Thus, it appears that T cells are relatively resistant to the effects of propanil and DCA, whereas, other immune cell types, e.g., NK cells are sensitive to its effects.

Aniline Compounds↗

Cellular localization of cytochrome P450IIA1 in testes of mature Sprague-Dawley rats.

Previous studies have shown that a prominent site of extrahepatic cytochrome P450IIA1 in male rats is the testis. We investigated the cellular location of cytochrome P450IIA1 in the testes of adult rats. Using specific isolation of testicular compartments and individual cell types, as well as in vivo removal of Leydig cells by ethane dimethyl sulfonate, we determined the cellular location of cytochrome P450IIA1 using testosterone hydroxylation assay, Western immunoblotting, and immunohistochemical analysis. Enriched Leydig cell fractions had the greatest testosterone 7 alpha-hydroxylase activity as well as immunoreactivity. Immunohistochemical analysis confirmed that the cellular location of cytochrome P450IIA1 was specific to Leydig cells. The specific localization of enzyme systems that are involved in xenobiotic activation may have important implications for inducing specific cell toxicity by compounds that exert their effects in the testes.

Animals↗

Alteration of fetal liver colony formation by prenatal chlordane exposure.

Female mice were treated with 0 or 8 mg/kg chlordane daily for 18 days during pregnancy. The fetuses of these mice were assayed for fetal liver hematopoietic activity at 18 days gestational age. Hematopoietic activity was evaluated for in vitro granulocyte-macrophage colony-forming units (GM-CFU) and in vivo spleen CFU (CFU-S). The consistent finding was a significant depression of the numbers of both fetal liver GM-CFU and CFU-S without a change in liver cellularity in fetuses exposed to 8 mg/kg chlordane. These data show that the damage to stem cells that persists into adult life as a result of chlordane exposure, as reported earlier by Barnett et al. (1990) Fundam. Appl. Toxicol. 14, 688-695, occurred during the fetal period.

Aging↗

Long-term alteration of adult bone marrow colony formation by prenatal chlordane exposure.

Female mice were treated with either 0, 4, or 8 mg of chlordane per kilogram body weight daily for 18 days during pregnancy. The offspring of these mice were assayed for bone marrow hematopoietic activity at 100 and 200 days of age. Hematopoietic activity was evaluated for in vitro granulocyte-macrophage colony-forming units (GM-CFU) and in vivo spleen CFU (CFU-S). The consistent finding was a significant depression both of the numbers of bone marrow GM-CFU and of the CFU-S in offspring exposed to either 4 or 8 mg/kg chlordane even at 100 and 200 days after cessation of treatment. Prenatal treatment with chlordane did not affect the number of recoverable viable bone marrow cells at either of these time points. Ontological development was selectively affected by chlordane exposure, since subchronic (18 day) treatment of adult mice did not significantly alter bone marrow GM-CFU or CFU-S levels. These data suggest that the decreased delayed-type hypersensitivity reactions noted previously in mice exposed to chlordane prenatally may be due to a change in the functional capacity of myeloid lineage cells rather than altered T cell function.

Animals↗