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M C Reid

Publications and source records attributed to M C Reid.

At least 37 records · Page 2Linked to original sources
PubMed1984

Increased immunoreactive erythropoietin in serum and kidney extracts.

Radioimmunoassay of erythropoietin (epo) was performed upon serum samples and kidney extracts from rats that received intrarenal injections of nickel subsulfide (Ni3S2, 20 mg/rat). Serum epo concentrations were significantly increased from 1 to 4 weeks after Ni3S2 injection; the highest values occurred at 3 weeks, when serum epo in 5 Ni3S2-treated rats averaged 230 mU/ml (range = 94 - 370 mU/ml); for comparison, serum epo in 21 vehicle-treated controls averaged 19 mU/ml (range = less than 14 - 56 mU/ml, P less than 0.01). In kidney extracts of 5 rats killed 3 weeks after Ni3S2 injection, epo concentrations averaged 970 mU/g (range = 210 - 1880 mU/g); for comparison, epo in kidney extracts of 6 controls averaged 99 mU/g (range = 40 - 140 mU/g, P less than 0.005). These radioimmunoassays confirm previous bioassays findings that serum epo concentrations are significantly increased in rats with Ni3S2-induced erythrocytosis. Contrary to bioassay findings, this study demonstrates increased immunoreactive epo concentrations in kidney extracts of Ni3S2-treated rats, suggesting that renal epo in Ni3S2-treated rats occurs in a form that lacks biological activity in vivo.

Animals↗
PubMed1983

Nickel induction of microsomal heme oxygenase activity in rodents.

Heme oxygenase activity was measured in tissues of rats killed after administration of NiCl2 or Ni3S2. Induction of renal heme oxygenase activity occurred 6 hr after NiCl2 injection (0.25 mmol/kg, sc), reached a maximum of five to six times the baseline activity at 17 hr, and remained significantly increased at 72 hr. Heme oxygenase activities were also increased in liver, lung, and brain at 17 hr after the NiCl2 injection; heme oxygenase activities in spleen and intestinal mucosa were unchanged. The effects of NiCl2 on heme oxygenase activities in kidney and liver were dose-related from 0.06 to 0.75 mmol/kg, sc. Three Ni chelators were administered (1 mmol/kg, im) prior to injection of NiCl2 (0.25 mmol/kg, sc); d-penicillamine partially prevented Ni induction of renal heme oxygenase activity; triethylenetetramine had no effect; sodium diethyldithiocarbamate enhanced the Ni induction of renal heme oxygenase activity (three times greater than NiCl2 alone). Intrarenal injection of Ni3S2 (10 mg/rat) caused induction of renal heme oxygenase activity at 1 week but not at 2, 3, or 4 weeks; no correlation was observed between induction of renal heme oxygenase activity and erythropoietin-mediated erythrocytosis. Hypoxia (10% O2, 12 hr/day, 7 days) did not affect renal heme oxygenase activity. Induction of renal heme oxygenase activity was observed in mice, hamsters, and guinea pigs killed 17 hr after injection of NiCl2 (0.25 mmol/kg, sc). These studies established (a) the time course, dose-effect, organ selectivity, and species susceptibility relationships for Ni induction of microsomal heme oxygenase activity, (b) the effects of Ni chelators, and (c) the lack of relationship between induction of renal heme oxygenase activity and the erythrocytosis that develops after intrarenal injection of Ni3S2.

Animals↗
PubMed1983

Synergistic induction of microsomal heme oxygenase activity in rat liver and kidney by diethyldithiocarbamate and nickel chloride.

Microsomal heme oxygenase activity was measured in liver and kidney of rats killed after administration of sodium diethyldithiocarbamate (DDC) and nickel chloride (NiCl2), singly and in combinations (DDC dosages: 0.33 to 1.33 mmol/kg, im, 17 hr before death; NiCl2 dosages: 0.125 and 0.25 mmol/kg, sc, 17 hr before death). Synergistic induction was observed at all dosage combinations. At the highest dosages of DDC and NiCl2, the dual treatments induced heme oxygenase activity 11-fold in liver and 16-fold in kidney; at the same dosages given individually, DDC induction of heme oxygenase activity was 3-fold in liver and 2-fold in kidney, and NiCl2-induction was 1.3-fold in liver and 6-fold in kidney. Synergistic induction of heme oxygenase activity in liver occurred when DDC was injected 6 hr before to 6 hr after NiCl2; synergistic induction in kidney occurred when DDC was injected 6 hr before to 3 hr after NiCl2. Actinomycin D prevented the induction of heme oxygenase activity by DDC or NiCl2, given individually; the effect of actinomycin D on synergistic induction could not be measured, since the rats all died following treatment with DDC, NiCl2, and actinomycin D. Administration of cysteine to rats, po, 18 hr before death, partially suppressed the induction of hepatic heme oxygenase activity by DDC, singly or in combination with NiCl2. Synergistic induction of hepatic heme oxygenase activity also occurred in rats that received dual injections of DDC (1.33 mmol/kg, im) and hemoglobin (0.3 g/kg, iv); the synergism of DDC and hemoglobin, although statistically significant, was small in comparison to the striking synergistic effect of DDC and NiCl2.

Animals↗
PubMed1983

Microcosm and experimental pond evaluation of microbial community response to synthetic oil contamination in freshwater sediments.

A multivariate approach was used to evaluate the significance of synthetic oil-induced perturbations in the functional activity of sediment microbial communities. Total viable cell densities, ATP-biomass, alkaline phosphatase and dehydrogenase activity, and mineralization rates of glucose, protein, oleic acid, starch, naphthalene, and phenanthrene were monitored on a periodic basis in microcosms and experimental ponds for 11 months, both before and after exposure to synthetic oil. All variables contributed to significant discrimination between sediment microbial responses in control communities and communities exposed to a gradient of synthetic oil contamination. At high synthetic oil concentrations (4,000 ml/12 m), a transient reduction in sediment ATP concentrations and increased rates of oleic acid mineralization were demonstrated within 1 week of exposure. These transient effects were followed within 1 month by a significant increase in rates of naphthalene and phenanthrene mineralization. After initial construction, both control and synthetic oil-exposed microbial communities demonstrated wide variability in community activity. All experimental microbial communities approached equilibrium and demonstrated good replication. However, synthetic oil perturbation was demonstrated by wide transient variability in community activity. This variability was primarily the result of the stimulation of polyaromatic hydrocarbon mineralization rates. In general, microcosms and pond communities demonstrated sufficient resiliency to recover from the effects of synthetic oil exposure within 3 months, although polyaromatic hydrocarbon mineralization rates remained significantly elevated.

Journal Article↗
PubMed1983

High-performance size-exclusion chromatography of 63Ni-constituents in renal cytosol and microsomes from 63NiCl2-treated rats.

Fractionations of 63Ni-constituents were performed by high-performance size-exclusion chromatography upon samples of renal cytosol and washed renal microsomes from rats that were killed 1 h after an im injection of 63NiCl2 (50 or 125 mumol/kg body wt). The kidney homogenates contained 2.0 +/- 0.4% of the total dose of 63Ni. Renal cytosol contained 55 +/- 5% and washed microsomes contained 5.4 +/- 1.2% of 63Ni that was present in the kidney homogenates. Chromatography of renal cytosol on TSK-GEL SW-2000 and SW-3000 separated 63Ni into six fractions. The largest component (Fraction F) contained approximately 80% of cytosolic 63Ni. Since Fraction F was eluted near the total permeation volume of SW-2000 columns and beyond the total permeation volume of SW-3000 columns, its molecular weight could not be reliably estimated. The other components, which comprised collectively the remaining 20% of cytosolic 63Ni, had apparent molecular weights of 168,000 (Fraction A), 84,000 (Fraction B), 51,000 (Fraction C), 24,000 (Fraction D), and approximately 10,000 (Fraction E). Solubilized washed microsomes from kidneys of 63NiCl2-treated rats contained 63Ni in five components with elution profiles and 63Ni-contents that resembled Fractions A, B, D, E, and F of renal cytosol, based upon chromatography on SW-3000 columns. The solubilized microsomes also contained a 63Ni-component with high molecular weight (Fraction M, greater than 700,000 daltons), which accounted for 3% of microsomal 63Ni. This study provides a rapid, convenient, and reproducible technique to fractionate 63Ni-components in tissue extracts, and it demonstrates in vivo binding of 63Ni to several constituents of renal cytosol and microsomes from 63NiCl2-treated rats.

Animals↗
PubMed1982

Effects of unilateral nephrectomy on erythrocytosis and arteriosclerosis induced in rats by intrarenal injection of nickel subsulfide.

Administration of Ni3S2 to rats by unilateral inrarenal (ir) injection (5 mg/rat) caused erythrocytosis, arteriosclerosis, and abnormal plasma concentrations of asparagine, glycine, histidine, and lysine. Resection of the ipsilateral (Ni3S2-treated) kidney on the fourth day after the ir injection prevented erythrocytosis, amino acid disturbances, and severe arteriosclerotic lesions (fibrous intimal plaques and focal medial necrosis), but did not prevent early arteriosclerotic lesions (subintimal oedema with splitting of elastica). The early arteriosclerotic lesions appear to be initiated by vascular dissemination of Ni3S2 particles immediately post-injection, whereas the erythrocytosis, amino acid disturbances, and advanced arteriosclerotic lesions depend upon continued presence of the Ni3S2-injected kidney. Resection of the contralateral (non-injected) kidney has no effect upon Ni3S2-induced erythrocytosis, arteriosclerosis, or amino acid disturbances. Glomerulomegaly and mesangial hyperplasia developed in control rats following unilateral nephrectomy, owing to compensatory renal hypertrophy. Glomerulomegaly was more pronounced in Ni3S2-treated rats following contralateral nephrectomy than following ipsilateral nephrectomy, suggesting that erythrocytosis and compensatory renal hypertrophy act synergistically to enhance glomerulomegaly.

Animals↗
PubMed1982

Gas-chromatographic assay for heme oxygenase activity.

We have developed an improved assay for microsomal heme oxygenase activity, based on the enzymic release of CO from the alpha-methene bridge of hemin and the quantitation of CO by gas chromatography. The within-run coefficient of variation (CV) of heme oxygenase assays in microsomes from rat tissues (liver, kidney) averaged 8%; the between-run CV averaged 15%. The detection limit for heme oxygenase activity was approximately 1 nmol/h per milligram of microsomal protein. Gas-chromatographic assays of heme oxygenase activities in rat tissues correlated well (r = 0.94) with results by a spectrophotometric assay based on bilirubin production. In untreated rats, heme oxygenase activity averaged 7 +/- 3 nmol/h per milligram of protein (n = 36) in kidney microsomes and 14 +/- 5 nmol/h per milligram of protein (n = 17) in liver microsomes. Heme oxygenase activity was increased 10-fold in kidney microsomes and threefold in liver microsomes from rats killed 17 h after subcutaneous injection of NiCl2 (0.5 mmol/kg body wt). These findings illustrate the efficacy of the gas-chromatographic assay for measuring xenobiotic effects on heme oxygenase activity.

Animals↗
PubMed1982

Induction of ocular neoplasms in Fischer rats by intraocular injection of nickel subsulfide.

Nickel subsulfide, alpha Ni3S2, was administered to albino Fischer rats by a single injection into the vitreous body of the right eye (0.5 mg alpha Ni3S2/rat, suspended in 20 microliter of NaCl vehicle). Control rats received a similar injection of the vehicle. Malignant tumors developed in the injected eyes of 14/15 alpha Ni3S2-treated rats by 8 months (vs. 0/11 controls, p less than 0.001). Five of the injected eyes of alpha Ni3S2-treated rats contained multiple tumors. The 21 eye tumors that were induced by alpha Ni3S2 included 11 melanomas, four retinoblastomas, three gliomas, and three unclassified malignant neoplasms. Three of the melanomas developed extraocular extensions; one of the melanomas metastasized to lungs and brain. Although the melanomas arose from amelanotic uveal melanocytes, melanosomes were observed in electron micrographs of the tumor cells. This study provides a new experimental model for chemical induction of ocular neoplasms. As a procedure to test the carcinogenicity of nickel compounds, intraocular injection has the advantages of short latency period, high tumor incidence, and ease of tumor detection.

Animals↗
PubMed1980

Teratogenicity and embryotoxicity of nickel carbonyl in Syrian hamsters.

Nickel carbonyl was administered to groups of pregnant hamsters by inhalation (0.06 mg Ni(CO)4/liter/15 min) on days 4, 5, 6, 7, or 8 of gestation. The dams were killed on day 15 of gestation, and the fetuses were examined for malformations. Exposure to Ni(CO)4 on days 4 or 5 of gestation resulted in malformations in 5.5% (8/146) and 5.8% (10/171) of the progeny, respectively (P less than 0.05, versus 0/95 in controls). The proportions of litters with malformed fetuses were 33% (4/12) and 24% (4/17) in dams exposed to Ni(CO)4 on days 4 and 5 of gestation (P less than 0.05, versus 0/9 in litters of control dams). Progeny of dams exposed to Ni(CO)4 on days 4 and 5 included 9 fetuses with cystic lungs, 7 fetuses with exencephaly, 1 fetus with exencephaly plus fused rib, and 1 fetus with anophthalmia plus cleft palate. Hemorrhages into serous cavities were found in 18% (26/146) and 25% (42/171) of fetuses of dams exposed to Ni(CO)4 on days 4 or 5 of gestation. Such hemorrhages were not observed in controls. In progeny of dams exposed to Ni(CO)4 on days 6 or 7 of gestation, there was 1 fetus with fused ribs and there were 2 fetuses with hydronephrosis. In another experiment, pregnant hamsters were exposed to inhalation of Ni(CO)4 (0.06 mg/liter/15 min) on day 5 of gestation; these dams were permitted to deliver their litters and to nurse their pups. On the day of delivery, there was no significant difference in the average number of live pups in the Ni(CO)4-exposed litters compared to control litters. Neonatal mortality was increased in Ni(CO)4-exposed litters; by day 4 postpartum, the number of live pups averaged 7.6 +/- 1.5 in Ni(CO)4-exposed litters (P less than 0.01 versus 9.6 +/- 1.8 pups in control litters). This study demonstrates that Ni(CO)4 is teratogenic and embryotoxic in Syrian hamsters.

Abnormalities, Drug-Induced↗
PubMed1980

Manganese inhibition of sarcoma induction by benzo[a]pyrene in rats.

The effects of Mn and Cr dusts upon carcinogenesis by polycyclic aromatic hydrocarbons were tested in male Fischer 344 rats. In Experiment I, rats were given i.m. injections of benzo[a]pyrene (BP, 1.2 mg), Mn dust (4.4 mg), and Cr dust (4.4 mg), alone, and in various combinations. By 100 weeks, sarcomas occurred at the injection site in 17/20 rats that received BP alone, versus 10/19 rats that received BP plus Mn dust (P < 0.05). The sarcoma incidences were 0/20 in 3 control groups that received the vehicle, Mn dust alone, or Cr dust alone, and 20/20 in rats that received BP plus Cr dust. In Experiment II, rats were given i.m. injections of BP (0.6 mg), 7,12-dimethylbenz[a]anthracene (DMBA, 0.6 mg), Mn dust (4.4 mg), and Cr dust (4.4 mg), alone, and in various combinations. Local sarcomas occurred in 17/20 rats that received BP alone, versus 5/17 rats that received BP plus Mn dust (P < 0.001). Sarcoma induction was not inhibited when BP was injected in the right thigh and Mn dust in the left thigh (sarcoma incidence = 16/20). The sarcoma incidences were 0/19 in a vehicle control group; 0/18 in 2 control groups that received Mn dust or Cr dust alone; 18/20 in rats that received BP plus Cr dust; 14/20 in rats that received DMBA alone; 17/19 in rats that received DMBA plus Mn dust; and 13/18 in rats that received DMBA plus Cr dust. These experiments show that Mn dust inhibits the carcinogenicity of BP when the Mn dust and BP are administered to rats by a single i.m. injection. Under identical conditions, Mn dust does not affect the carcinogenicity of DMBA; Cr dust does not affect the carcinogenicity of BP or DMBA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

In utero fetal lamb thyroidectomy and thyroid autograft transplantation.

Our fetal surgical model was utilized to perform in utero fetal lamb thyroidectomy and autograft transplantation of thyroid tissue to fetal thigh at 82-93 days gestation. Successful in utero transplantation was possible in two of six experimental animals. In one twin pregnancy with an unoperated control lamb, observations were continued to age six months. The athyrotic lamb with a thigh autograft was larger at birth and had a transient weak sucking reflex and awkward gait. It then grew and developed normally with no stigmata of cretinism or delay in bone maturation. At age six months an increase in thyroid stimulating hormone (oTSH) was the single distinguishing observation in the twin with the transplant. Although oTSH levels were elevated to age six months, the pituitary continued to be responsive to thyrotropin releasing hormone (TRH) stimulation. These findings suggest that in utero transplantation of thyroid tissue is technically feasible and that the previously described development of in utero cretinism following fetal thyroidectomy can be prevented by a functioning autograft. This technique will be useful in attempting allograft transplantation in utero.

Animals↗
PubMedDate not supplied

Hazardous and harmful alcohol consumption in primary care.

Increasing emphasis has been placed on the detection and treatment of hazardous and harmful drinking disorders, particularly among patients who are seen in primary care settings. In this review, we summarize the epidemiology and health-related effects of hazardous and harmful drinking and discuss current methods for their detection and treatment. Hazardous drinking is defined as a quantity or pattern of alcohol consumption that places patients at risk for adverse health events, while harmful drinking is defined as alcohol consumption that results in adverse events (e.g., physical or psychological harm). Prevalence estimates range from 4% to 29% for hazardous drinking and from less than 1% to 10% for harmful drinking. Data from several recent large prospective studies suggest that alcohol consumption in quantities consistent with hazardous or harmful drinking may increase risk for adverse health events, such as hemorrhagic stroke and breast cancer. Existing screening instruments, such as the Michigan Alcoholism Screening Test (MAST) or the CAGE questionnaire, while excellent for detecting alcohol abuse or dependence, should not be used alone to screen for hazardous and harmful drinking. The Alcohol Use Disorders Identification Test (AUDIT) is currently the only instrument specifically designed to identify hazardous and harmful drinking. Treatment of these disorders in the form of brief interventions can be successfully accomplished in primary care settings, as demonstrated by a number of well-conducted randomized trials. Given its proven efficacy in the primary care setting, we recommend routine application of this treatment approach.

Alcohol Drinking↗
PubMedDate not supplied

Hepatic toxicity of nickel chloride in rats.

Enhanced lipid peroxidation was observed in livers of rats killed 24 hr after sc injection of nickel chloride (NiCl2) (750 mumol per kg), as evidenced by 13-fold increase of conjugated dienes in microsomal lipids and 4-fold increase of thiobarbituric acid (TBA) chromogens in hepatic cytosol. Histologic examination of livers from rats killed one to three days after NiCl2 injection (500 mumol per kg) showed microvesicular fatty metamorphosis, mild hydropic degeneration, and foci of inflammation. Microvesicular steatosis of hepatocytes was confirmed by electron microscopy. Dose-related increases of serum aspartate aminotransferase (ALT) activity (up to 7-fold vs controls) and alanine aminotransferase (ALT) activity (up to 3-fold vs controls) were observed 24 hr after injection of NiCl2 (125 to 750 mumol per kg); diminished serum alkaline phosphatase activity (up to 72 percent reduction vs controls) was seen at NiCl2 dosages from 375 to 750 mumol per kg. Diethyldithiocarbamate did not influence the effects of NiCl2 on TBA-chromogens in liver homogenates or on serum AST and ALT activities but acted synergistically with NiCl2 to diminish serum alkaline phosphatase activity and to increase serum bilirubin concentration. This study demonstrates that parenteral administration of NiCl2 to rats produces acute hepatic toxicity, with enhanced lipid peroxidation, microvesicular steatosis, and increased serum AST and ALT activities.

Alanine Transaminase↗
PubMedDate not supplied

Ethene (ethylene) and ethane exhalation in Ni[II]-treated rats, using an improved rebreathing apparatus.

To assess the effects of NiCl2 on lipid peroxidation, exhalation rates of ethene (ethylene) and ethane were measured in Fischer-344 rats, using modifications of a recently published rebreathing apparatus and gas chromatographic assay. Technical improvements included more efficient removal of H2O vapor, NH3, and CO2, use of economical, readily available components, convenient standardization procedure, and no necessity for a charcoal concentrator accessory for the gas chromatograph. The detection limit was one pmol ethene or ethane per five mL air sample; the within-run precision (CV) of analysis was 2.1 percent at an ethane concentration of 16 pmol per five mL sample. A minimum of eight hours post-injection was necessary for exhalation rates of ethene or ethane to become significantly increased in NiCl2-treated rats. Ethene exhalation rate was increased 2.0- to 3.5-fold at 13 to 16 and 20 to 23 hours after NiCl2 injection (0.50 or 0.75 mmol per kg, body wt, sc). Ethane exhalation rate was increased 1.5- to 1.6-fold at the lower dosage, but was not significantly increased at the higher dosage of NiCl2. This study corroborates previous reports that lipid peroxidation is enhanced in target tissues (liver, kidney, lung) of NiCl2-treated rats.

Animals↗