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Biomedical subjects

M Root

Publications and source records attributed to M Root.

14 recordsLinked to original sources
PubMed1997

Dissimilarity in aflatoxin dose-response relationships between DNA adduct formation and development of preneoplastic foci in rat liver.

Earlier work in this laboratory and that carried out by others demonstrated that after a single dose of aflatoxin B1 (AFB) the resulting liver AFB-DNA adduct levels were directly proportional to dose. Earlier work also showed that after ten daily doses the AFB dose-response relationship with gamma-glutamyl transpeptidase (GGT) positive preneoplastic foci measured at 3 months was sublinear, with a threshold at a dose of about 150 micrograms/kg body weight/day. The objective of this study is to determine the factors influencing the shift in AFB dose-response between AFB-DNA adducts and GGT foci. Male Fisher 344 weanling rats were orally administered one or ten doses of AFB ranging from 50 to 350 micrograms/kg body weight/day. The animals were killed 2 or 24 h after the first AFB dose, or after the tenth AFB dose. The first and tenth doses were tritiated in these animals and 3H-AFB-guanine adducts isolated from liver DNA were measured by HPLC. Another group was killed 3 months after receiving ten doses in order to measure GGT foci development. AFB-guanine adduct levels were directly proportional to dose after the first dose, but after the tenth dose were much lower in the 200-350 micrograms/kg groups than after a single dose. The GGT foci response confirmed earlier work concerning a sublinear response. Among the individual animals in the 200-350 micrograms/kg groups there was a positive relationship, after controlling for dose, between GGT foci development and weight gained both during dosing (P = 0.018) and also to a lesser extent during the early promotional period (P = 0.066). Enzyme activity levels of GGT in liver homogenates were higher in the highest dose groups and reflected biliary proliferation rather than histological GGT stained foci. Urinary levels of AFB metabolites changed proportions in the high dosage multiply dosed animals reflecting alteration in AFB metabolism or excretion. The differences between the linear adduct and the sublinear foci dose-response curves may be the result of non-adduct effects of higher multiple AFB doses on foci formation including acute cytotoxicity, altered AFB metabolism and disposition, enhanced weight gains, or shortened foci latency but not through enhanced guanine adduct levels. Other studies that showed a linear relationship between AFB dose and liver tumor development used continuous feeding of maximal doses an order of magnitude less than the lowest dose in this study and thus avoided acutely toxic effects. We hypothesize that liver tumor development may mirror foci response in a 10-dose AFB regimen with doses above 100 micrograms/kg due to acute toxicity effects.

Administration, Oral↗
PubMed1997

Use of an improved method for analysis of urinary aflatoxin M1 in a survey of mainland China and Taiwan.

An improved monoclonal antibody immunoaffinity chromatography/high-pressure liquid chromatography/ fluorescence detection method was developed to measure aflatoxin (AF) exposure by quantifying AFM1 in human and rat urine samples. Analysis of different amounts of various AF metabolites showed that the immunoaffinity resin was highly selective for aflatoxin B1 (AFB1), AFB2, and AFM1. Recovery of added AFs increased with the amount of immunoaffinity resin and was virtually complete within the range of 0.01-10 ng of AFM1 by using 7 ml of resin. The detection limit of this method is 0.5 pg/ml urine. Rats dosed with tritiated AFB1 excreted in their urine tritiated AFM1, among other AF metabolites, as indicated by chemical derivative confirmation and cochromatography with authentic AFM1 and agreement of radioactivity and fluorescence quantitation. A linear dose-response relationship was found over the range of 0.05-50 micrograms/kg of body weight/day. Two humans dosed with 1.0 microgram of pure AFB1 excreted 6-7% of the dose as urinary AFM1 over 5-7 days. Pooled urine samples from 30 men from each of 69 rural counties in mainland China and 16 survey areas in Taiwan, with two villages per county or area, were analyzed with this improved method (170 villages total). The correlation coefficient of urinary excretion of AFM1 compared between villages within all 85 survey areas was 0.50 (P < 0.001). Sixty-five % of the samples contained detectable concentrations of AFM1 with an average excretion of 3.1 ng/12 h. Assuming an excretion rate of 2-6%, this AFM1 excretion corresponds to a very low average daily AF consumption of 0.1-0.3 microgram/day (possible range, 0-11 micrograms/day). Patterns of urinary excretion of AFM1 were similar in mainland China and Taiwan.

Adult↗
PubMed1996

Vitamin A and carotenoid status in rural China.

Vitamin A status of 260 groups of twenty-five males or twenty-five females, aged 35-64 years, surveyed in twenty-four provinces of the People's Republic of China, was assessed by measuring plasma retinol. retinol-binding protein and beta-carotene concentrations. Direct measurements of food intake over a 3 d period and questionnaire data on the frequency of consumption of vegetables, fruits, animal products and other dietary items were also used. Vitamin A status appeared to be low only in specific counties but in general was satisfactory or only marginally deficient. Plasma beta-carotene levels were strikingly low in comparison with Western levels despite generous vegetable consumption suggesting that intake of vitamin A precursors may have been adequate but not abundant enough to maintain high circulating plasma levels of beta-carotene. Plasma beta-carotene, for both males and females, was significantly correlated with the frequency of consumption of green vegetables. Plasma retinol, for males, was highly correlated with meat, fish, oil and alcohol consumption expressed both in quantity or frequency of consumption. Higher levels of plasma retinol, together with lower levels of plasma beta-carotene in males compared with females, suggest that men consume more animal products or may have higher retinol requirements and therefore a higher rate of conversion of beta-carotene to retinol.

Adult↗
PubMed1993

Antisense DNA inhibition of tumor growth induced by c-Ha-ras oncogene in nude mice.

Antisense DNA has shown an ability to target specific oncogene transcripts and inhibit their expression in cells, but the degree to which sustained treatment can suppress total levels of an oncogenic product and alter tumorigenesis in vivo remains to be determined. In this study, NIH-3T3 cells transformed by the activated c-Ha-ras oncogene from T24 human bladder cancer cells were treated for 3 consecutive days in vitro with an antisense DNA pentadecamer complementary to a target in the 5'-flanking region of the c-Ha-ras RNA transcript. Following antisense DNA treatment, a portion of the cells was lysed for measurement of RAS p21 while the remaining cells were evaluated for tumorigeneity by injection s.c. into athymic nude mice at a dose of 5 x 10(5) cells/mouse. The 3 days of treatment with the anti-c-Ha-ras DNA reduced RAS p21 cellular levels by more than 90% while a nonspecific control DNA reduced p21 levels by approximately 20%. Tumor growth of cells treated with anti-c-Ha-ras DNA was significantly reduced for up to 14 days following the end of treatment and implantation into the mice whereas the nonspecific control DNA had no significant effect. These effects on tumor growth were evident in two different strains of nude mice and in both males and females. It is suggested that the pronounced decrease in RAS p21 levels produced by anti-c-Ha-ras DNA resulted in a reversal of the transformed phenotype, and it is this reversal which accounts for the prolonged inhibition of tumorigenesis following antisense DNA treatment.

3T3 Cells↗
PubMed1992

Long-term followup with the use of lyophilized dura mater for abdominal wall closure in children: report of 3 cases.

We report our experience with 3 children treated during infancy by abdominal wall reconstruction using lyophilized dura mater. Followup has been 36, 46 and 96 months postoperatively and they demonstrated adequate abdominal wall healing. One child has mild muscular diastasis, while 1 has completely healed. In 1 child a small defect developed in the repair, which was closed at a secondary procedure. Wound infection, dehiscence or herniation did not occur. There has been no evidence of Creutzfeldt-Jakob disease, which has been reported when allogenic dura was not obtained from registered tissue banks. Our experience with dura mater suggests that the material may be a useful adjunct in the repair and closure of complex abdominal defects.

Abdominal Muscles↗
PubMed1990

Burkitt's lymphoma of the testicle: report of 2 cases occurring in elderly patients.

Burkitt's lymphoma is rare in patients older than 50 years and almost never presents as a testicular tumor. We report 2 cases of primary Burkitt's lymphoma of the testicle in men 68 and 79 years old. In 1 man the extragonadal tumor had a rapid and lasting response to combination chemotherapy. The cases are of interest for the unusual presentation of the disease and for the possibility to control Burkitt's lymphoma in older patients without undue toxicity. The management of testicular lymphoma requires radical orchiectomy and prophylactic irradiation of the contralateral testis. Chemotherapy is indicated for advanced disease and may prevent relapses in patients with early disease. The role of central nervous system prophylaxis is controversial.

Aged↗
PubMed1990

Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A.

A case-control study of breast cancer was conducted in Buffalo. Participants completed a food frequency questionnaire and donated a fasting blood sample before definitive workup for breast masses. Dietary and plasma concentrations of carotenoids and retinol for 83 women found to have breast cancer were compared with those of 113 women found to be free of breast cancer (control subjects). There were no case-control differences in dietary estimates of vitamin A intake or in plasma alpha-carotene and lycopene. However, subjects with breast cancer had lower concentrations of plasma beta-carotene than did control subjects (P = 0.02). There was no overall association between plasma retinol and breast cancer but a positive relationship was observed between retinol and breast cancer in the subgroup with low beta-carotene values. These results suggest that low plasma beta-carotene is associated with increased risk of breast cancer. Other studies will need to determine whether low carotene concentrations are a subtle effect of the disease or might be causally related to breast cancer.

Adult↗
PubMed1978

Activity analysis of operant behavior following methylphenidate administration.

13 male Long-Evans hooded rats were tested on a CRF-50 reinforcement schedule. Total response time as well as time and total activity responses away from the bar were significantly influenced by injections of methylphenidate (1.2 mg/kg I.P.). In general, the data supported previous findings of reduced response rate to the drug. However, methylphenidate (a CNS stimulant) increased activity that was not related to bar pressing. Analysis of activity response to drug should include total time and activity as well as operant rates.

Animals↗
PubMed1975

Enzymatic degradation of heparin-related mucopolysaccharides from the surface of endothelial cell cultures.

When cultures of endothelial cells prelabeled with H2 -35-SO4 are exposed to a purified preparation from induced Flavobacterium heparinum containing heparinase and heparitinase activities, radioactivity accumulates in the supernatant medium. After further treatment in vitro with crude enzyme this material migrates, in part, as glucosamine (N,O-disulfated glucosamine), a break-down product characteristic of heparin and heparin-related mucopolysaccharides. After exposure of the cultures to the purified enzyme, the amount of acid-insoluble -3 5-S radioactivity that can be removed with EDTA is decreased compared to that that can be removed from control cultures. Since the amount of radioactivity that is released as break-down products is much higher than the amount of radioactivity that is secreted into the supernatant medium as intact (non-dialysable) mucopolysaccharide chains in control plates, the action of the enzyme appears to be on the cell itself. The data presented support previous studies suggesting that chains of heparitin sulfate that are accessible to the action of the enzyme are present at the surface of endothelial cells.

Cells, Cultured↗
PubMedDate not supplied

Plasma insulin and C-peptide after subcutaneous and intravenous administration of human insulin (recombinant DNA) and purified porcine insulin in healthy men.

We have compared the plasma profiles of C-peptide, human insulin (recombinant DNA), and purified porcine insulin of pancreatic origin (PPI) in six nondiabetic men after low-dose (4.8 U) or high-dose (9.6 U) subcutaneous injection and low-rate (1.0 U/h) or high-rate (1.7 U/h) intravenous infusion. There was no significant difference in plasma C-peptide or glucose levels when human insulin was compared with PPI at either dose level for subcutaneous injection or intravenous infusion. Thus, there was equal suppression of endogenous insulin by the two species of exogenous insulin. For low-dose subcutaneous injection there was no significant difference between plasma insulin levels of the two species at single time points or when areas were compared. For high-dose subcutaneous injection mean plasma insulin levels were higher after human insulin than after PPI (20-300 min); this serial difference reached conventional statistical significance at 50 min (P less than 0.05) and 90 min (P less than 0.01). For the area under plasma insulin profiles between 0 and 90 min after high-dose s.c. injection, human insulin was higher than PPI (P = 0.06). There was no significant difference between insulin concentrations after human insulin and PPI given by either low- or high-dose intravenous infusion, except that high-dose PPI values (55-110 min) were slightly but significantly higher after high-dose intravenous infusion. Further comparisons of the pharmacokinetics of human and other species of insulin are, therefore, justified in larger numbers of subjects and particularly in diabetic individuals.

Animals↗
PubMedDate not supplied

Effects of breast cancer treatments on plasma nutrient levels: implications for epidemiological studies.

The interpretation of case-control studies in which blood nutrient levels are examined as etiological factors in cancer is complicated by the possibility that either the disease or its treatment may alter these levels. Circulating levels of selected nutrients were examined prior to diagnostic biopsy and compared with levels 3 to 4 months after diagnosis among 71 women with breast cancer and 95 women with benign breast disease. Among women with benign breast disease or women with breast cancer who were not given postsurgical adjuvant drug therapy, levels of alpha-carotene, lycopene, alpha-tocopherol, cholesterol, and triglycerides did not change over time. In contrast, women who received chemotherapy had increased levels of cholesterol, retinol, and alpha- and gamma-tocopherol, and women on antiestrogen therapy showed increased levels of triglycerides and alpha-tocopherol. Overall, the concentrations of carotenoids (lycopene, alpha-carotene, and beta-carotene) did not change in breast cancer cases, although subgroup analyses showed increased levels of beta-carotene among cases not receiving drug treatment and decreased levels among those receiving antiestrogens. In summary, blood levels of some nutrients did not appear to be affected by breast cancer or its treatments, but changes were noted for levels of plasma lipids, tocopherols, retinol, and beta-carotene. Those investigating the etiological relationship between breast cancer and circulating nutrients need to consider these effects in designing and interpreting epidemiological studies.

Adult↗