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Biomedical subjects

P B Conran

Publications and source records attributed to P B Conran.

At least 19 recordsLinked to original sources
PubMed2001

Effect of chloroform on dichloroacetic acid and trichloroacetic acid-induced hypomethylation and expression of the c-myc gene and on their promotion of liver and kidney tumors in mice.

Chloroform, dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are mouse liver carcinogens that are chlorine disinfection by-products found in drinking water. The effect of chloroform on DCA and TCA-induced hypomethylation and expression of the c-myc gene and on their promotion of liver and kidney tumors was determined. B6C3F1 mice were administered 0, 400, 800 and 1600 mg/l chloroform in drinking water and 500 mg/kg DCA or TCA-administered daily by gavage. DCA, TCA and to a lesser extent chloroform decreased the methylation and increased the mRNA expression of the c-myc gene. Co-administering chloroform prevented only DCA and not TCA-induced hypomethylation and increased mRNA expression of the gene. The effect of chloroform on tumor promotion by DCA and TCA was determined in female and male B6C3F1 mice initiated on day 15 of age with N-methyl-N-nitrosourea. Starting at 5 weeks of age, the mice received in their drinking water DCA (3.2 g/l) or TCA (4.0 g/l) with 0, 800 or 1600 mg/l chloroform until they were killed at 36 weeks. Liver tumors promoted by DCA and TCA were predominantly basophilic except for DCA-treated female mice that were eosinophilic. Only DCA promoted foci of altered hepatocytes and they were eosinophilic in both sexes. Chloroform prevented DCA, but not TCA promotion of liver foci and tumors. In male mice, TCA promoted kidney tumors while DCA promoted kidney tumors only when co-administered with chloroform. Hence, chloroform prevented the hypomethylation and increased mRNA expression of the c-myc gene and the promotion of liver tumors by DCA, while enhancing DCA-promotion of kidney tumors. Thus, the concurrent exposure to two carcinogens, chloroform and DCA resulted in less than additive activity in one organ and synergism in another organ.

Animals↗
PubMed2000

Asthma severity, psychophysiological indicators of arousal, and immune function in asthma patients undergoing biofeedback-assisted relaxation.

Asthma is characterized by airway hyper-responsiveness, inflammation, and reversible obstruction. Respiratory tract infection, allergies, air pollution, and psychosocial factors impact the severity and frequency of asthma symptoms. Pharmacotherapy and self-care are the major components in the management of asthma, but behavioral interventions also have the potential to affect asthma morbidity. We conducted a small, randomized controlled study, examining the effects of biofeedback-assisted relaxation in 16 nonsmokers with nonsteroid-dependent mild asthma. Data were collected on asthma symptoms, pulmonary function, indicators of arousal, and cellular immune factors. The trained group evidenced a decrease in forehead muscle tension in comparison to the controls, but no changes in peripheral skin temperature. Decreases in asthma severity and bronchodilator medication usage for the experimental group were observed. Pulmonary function testing revealed a significant difference between groups in FEV1/FVC at posttest, with the E group having a higher ratio than the controls. The cellular immune data showed no significant group differences in total white blood cell or lymphocyte counts, but decreases over time were observed. Significant differences were observed in the numbers of neutrophils and basophils in the trained group compared to controls, which supports the concept of decreased inflammation. Results of delayed-type hypersensitivity skin testing suggested enhanced function, but they were not conclusive. These findings, though limited by size of population, suggest a positive effect of biofeedback-assisted relaxation in young, nonsteroid-dependent asthmatics. The mechanisms underlying linkages between psychological, behavioral, and immune responses in asthma require further study.

Adolescent↗
PubMed1996

O6-methylguanine levels and histopathological changes in the rat esophagus and liver following single and repeated administration of N-nitrosomethylbenzylamine.

In this study we investigated the time course of O6-methylguanine (O6-meGua) levels and concomitant histopathological effects in the rat esophagus and liver following single and repeated s.c. administration of the esophagus-specific carcinogen N-nitrosomethylbenzylamine (NMBA). The primary purpose of this study was to determine if differences in the induction and/or persistence of O6-meGua might account for differences in the tumorigenicity of NMBA observed with treatment regimens of 0.5 mg/kg/dose, 3 doses/week for 5 weeks (a proven tumorigenic regimen) and 1.67 mg/kg/dose, 3 doses/week for 2 weeks (an essentially non-tumorigenic regimen). Results of the single dose experiment indicated that enzymatic activation of NMBA in the rat esophagus was not dose limited, at least at doses up to and including 5.0 mg/kg. Results of the repeated dose experiment demonstrated that the non-tumorigenic NMBA regimen produced significantly higher levels of esophageal O6-meGua compared with the tumorigenic NMBA regimen. During the 2 week treatment period of the non-tumorigenic regimen esophageal O6-meGua levels decreased progressively, but remained significantly higher than in the tumorigenic regimen. In contrast, the relatively lower O6-meGua levels of the tumorigenic regimen remained essentially unchanged during the course of treatment. At 72 h following conclusion of dosing no O6-meGua was detected in the esophagi of rats treated with either regimen. Microscopic examinations revealed that the non-tumorigenic NMBA regimen produced a marked cytotoxic effect on the esophageal epithelium, while microscopic esophageal changes observed with the tumorigenic regimen were generally less severe. In the liver O6-meGua was detected in only a few rats and no remarkable microscopic pathology was observed in this organ. Together these findings indicate that: (i) abbreviated NMBA treatment induces tumors in the rat esophagus only at levels that induce DNA damage without causing extensive cytotoxicity; (ii) the lack of NMBA tumorigenicity in the rat liver may be due, at least in part, to the rapid and efficient repair of O6-meGua adducts, coupled with the lack of necrosis and compensatory cell division in this organ.

Animals↗
PubMed1991

Comparison of faculty members' and students' perceptions concerning performance criteria and evaluation strategies at the University of New Mexico School of Medicine.

Faculty members' and students' perceptions concerning the relative importances of (1) various performance criteria for students and (2) strategies of evaluation were determined in 1989 by a questionnaire in a single medical school that had both a problem-based, student-centered curriculum and an organ-block curriculum (i.e., regular track). The greatest differences in the rankings of both areas were found between those given by the freshman and sophomore students in the problem-based curriculum and those given by the same groups in the regular track. The faculty members' perceptions tended to be closer to those of the students in the regular track.

Attitude to Health↗
PubMed1989

Relationship between in utero development of the mouse liver and tumor development following transplacental exposure to ethylnitrosourea.

Pregnant C3HeB/FeJ mice were treated with ethylnitrosourea (ENU) on one of gestation Days 10, 13, or 15 to determine if ENU treatment at different stages of gestation would result in morphological or quantitative differences in liver tumors induced in the offspring. Liver tumors were counted and measured 6 mo after treatment with ENU. Foci of cellular alteration were identified histologically and counted. Liver tumor number and foci of cellular alteration increased as a function of increasing dose and age at the time of ENU treatment. An inverse relationship between age at the time of treatment and the size of liver tumors was found. The mean tumor volume of male mice exposed on Day 10 of gestation was 123-fold larger than for spontaneous tumors observed in controls. The differences between mean liver tumor volume in mice which had been exposed to ENU on Days 10, 13, or 15 of gestation appeared to be associated with the exponential growth of the fetus during this period of gestation. Unique, large, multinodular foci of cellular alteration were found in mice treated on Day 10 of gestation. The relationship between the stage of gestation and the size of chemically induced liver tumors in these mice is similar to previous observations with transplacentally induced lung tumors in C3HeB/FeJ mice. This indicates that developmentally regulated cell proliferation occurring at the time of carcinogen exposure may affect the subsequent extent of tumor development in both the liver and lung. Therefore, cells transformed during early development may result in tumors that pose a greater biological hazard than those transformed in later development.

Animals↗
PubMed1989

Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA adduct formation and tumorigenicity in the lung of F344 rats by dietary phenethyl isothiocyanate.

F344 rats fed diets containing phenethyl isothiocyanate (PEITC, 3 mumol/g diet), a cruciferous vegetable component, before and during treatment with the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), developed about 50% fewer lung tumors than NNK-treated rats fed control diets. NNK-induced liver and nasal cavity tumors in rats were, however, not affected by this dietary treatment. The effects of PEITC diets on the formation of DNA adducts by NNK were also investigated in these target tissues. DNA methylation and pyridyloxobutylation by NNK were both decreased by 50% in lung of rats fed PEITC diets compared to that of rats fed control diets, but the levels of DNA methylation were not affected in liver and nasal mucosa. These results correlated with those from the carcinogenicity bioassay, suggesting that DNA alkylations could be used as indicators for screening inhibitors of NNK tumorigenesis. A slight increase in the number of tumors of the exocrine pancreas was observed in PEITC-fed rats with or without NNK treatments. However, these incidences were not statistically significant when compared to the control groups. The potential toxicity of PEITC at concentrations ranging from 0.75 mumol to 6 mumol/g diet was evaluated in a 13-week study. The only toxicity caused by this treatment was minimal fatty metamorphosis in the liver. Considering the widespread human exposure to NNK through tobacco use, it is of practical importance to demonstrate inhibition of lung tumors induced by this carcinogen. These results provide a basis for studies designed to discover agents of better efficacy for the prevention of NNK-induced tumorigenesis.

Alkylation↗
PubMed1988

Effect of gestational development of lung tumor size and morphology in the mouse.

Pregnant C3HeB/FeJ mice were treated with ethylnitrosourea (ENU) on one of gestation Days 10, 13, or 15 to determine if ENU treatment at different stages of gestation would result in qualitative or quantitative differences in lung tumors induced in the offspring. Lung tumors were counted and measured 6 mo after treatment with ENU. Offspring of mice treated with ENU on Day 10 of gestation had a small increase in lung tumors while those treated on gestation Day 13 or 15 had significantly more tumors than controls and 6- to 8-fold more tumors than the treated mothers. An inverse relationship between age at the time of treatment and lung tumor size was found. The mean lung tumor volume of mice exposed on Day 10 of gestation was 167-fold larger than that of mice exposed to ENU as adults. The difference between mean lung tumor volume in mice which had been exposed to ENU on Day 10, 13, or 15 of gestation appeared to be associated with the exponential growth of the fetus during this period of gestation. Lung tumors induced on Days 10 and 13 of gestation were irregular in contour and were multinodular. Sixty-five to 85% of the lung tumors in offspring treated during gestation versus 20% in mice treated as adults had a papillary morphology. These differences in tumor size and morphology indicate that cells transformed during early development may pose a greater biological hazard than cells transformed in older animals.

Animals↗
PubMed1987

Ethylnitrosourea-induced transplacental carcinogenesis in the mouse: tumor response, DNA binding, and adduct formation.

We have confirmed previous results which suggest that transplacental exposure of fetal mice to carcinogens does not cause an increase in tumor incidence as they mature unless treatment occurs after midorganogenesis. In C3HeB/FeJ mice we found a negligible increase in tumor incidence and multiplicity following transplacental exposure to the direct-acting carcinogen ethylnitrosourea (ENU) on gestation day 10, but significant increases in lung and liver tumor incidence following exposure on days 13 or 15 or in adults. To explore the possibility that this observed difference is due to differences in the biodistribution of the carcinogen or its interaction with cellular macromolecules, the level of covalent binding between ENU and fetal and maternal DNA following an i.p. injection of a dose of 50 mg/kg of tritium-labeled ENU was measured 30 min after its injection into pregnant females on days 10, 13, and 15 of gestation. The DNA from fetal and maternal lung, liver, and brain was isolated and the amount of covalent binding estimated from the dpm/mg DNA recovered. Samples of DNA were hydrolyzed and chromatographed to determine that the bound tritium was associated with ENU-DNA adducts and not as a product of DNA synthesis. The level of binding of ENU to fetal DNA was equivalent at all gestation days studied but was significantly less than maternal tissues. Binding to the DNA of maternal liver was 4-fold greater than to fetal DNA while maternal lung and brain DNA were bound at intermediate levels. We conclude that the lack of carcinogenic response to ENU documented here, in fetal mice exposed early in gestation (day 10), is not due to differences in ENU binding to fetal DNA during development.

Adenoma↗
PubMed1986

Comparison of two routes of chemical administration on the lung adenoma response in strain A/J mice.

This study was undertaken to determine the ability of a series of 19 compounds representing different chemical classes of carcinogens to induce lung tumors in strain A/J mice after either ip or po administration. Aflatoxin B1, dibutylnitrosamine, 1,2-dimethylhydrazine, and methylnitrosourea induced a significant increase in the lung tumor response in both sexes after ip and po administration. Azaserine was active in both sexes only after ip administration. Benzene, 1,2-dibromoethane, and epichlorohydrin, following ip administration, produced significant increases in the tumor response in at least one sex. Aflatoxin B1, azaserine, benzene, 1,2-dibromoethane, dibutylnitrosamine, and epichlorohydrin were more active when given ip than after po administration. In contrast, dimethylhydrazine and methylnitrosourea were more active (in females only) when given po. 2-Acetylaminofluorene, azobenzene, chloroform, 1,4-dioxane, FANFT (N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide), lead subacetate, methylmethanesulfonate, beta-naphthylamine, beta-propiolactone, safrole, and 2,4,6-tri-chlorophenol did not induce lung tumors in strain A/J mice. These data confirm previous observations on the importance of the route of chemical administration on the lung tumor response in strain A mice, and on the inability of the lung tumor bioassay to detect certain liver and bladder carcinogens and unstable alkylating agents.

Adenoma↗
PubMed1986

How computers are used in pathology education.

How are computers being used to teach pathology? Of 129 major medical teaching institutions surveyed, 63 institutions responded and 37 were using computers in pathology education. Applications include examination, instruction and consultation, case simulation, and course evaluation.

Computer-Assisted Instruction↗
PubMed1984

Possible mechanistic roles of anatomical and functional vascular changes in rat urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine.

Anatomical and functional vascular changes during rat urinary bladder carcinogenesis were studied by scanning electron microscopy of vascular casts, transmission electron microscopy of bladder capillaries, and fractional distributions of 51Cr-erythrocytes, 125I-human serum albumin, and 86RbCl which were used to determine vascular volume, permeability, and perfusion. Histopathological changes and focal capillary changes in vascular casts were measured quantitatively by an image analyzer. Male Wistar rats received 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 8 weeks and were then maintained on tap water without BBN for an additional 32 weeks. Simple hyperplasia was first seen at Week 2. The percentage of the area of hyperplastic epithelium increased to about 95% by Week 8 and then decreased to 4 to 6% at Weeks 20 or 40. Papillary or nodular hyperplasia was first seen at Week 6. The percentage of the area of papillary or nodular hyperplasia increased with time to 31.0% at Week 40. Papillary transitional-cell carcinomas were found from Week 20, increasing with time, and their incidence was 100% after Week 35. Vascular cast diameters of normal-looking capillaries were larger during than after BBN treatment. Type 3 vascular proliferations were found beneath papillary or nodular hyperplasia and cancer. Capillaries beneath simple hyperplasia and type 3 capillaries beneath capillary or nodular hyperplasia and cancers were fenestrated and dilated. Changes in vascular volume were independent of changes in permeability and perfusion. Best-fit curve analyses showed the maximum vascular volume at 8 weeks and minimum at 25 weeks, and the permeability maxima at 4 and 25 weeks with minima at 15 and 32 weeks. While 86Rb values correlated 125I values (r = 0.58), they were unstable in intermediate time periods. Changes of vascular volume were coincident initially with increased areas of dilated capillaries beneath simple hyperplasia and later with areas of type 3 capillary proliferation beneath papillary or nodular hyperplasia and cancer. Changes of vascular permeability were related to inflammation indices throughout the study. Increases in permeability were coincident with fenestrated capillaries beneath simple hyperplasia in early stages, and subsequently with fenestrated type 3 capillaries beneath papillary or nodular hyperplasia and cancer. BBN appears to cause alterations in vascular volume via induction of capillary dilation and also possibly by enhancing the responsiveness of host endothelium to angiogenic stimulation from neoplastic or preneoplastic tissues.

Analysis of Variance↗
PubMed1984

Activated coagulation time test: a convenient monitor of heparinization for dogs used in cardiovascular research.

The usefulness of the activated coagulation time test to monitor heparin effect was studied by administering varying intravenous doses of heparin to six mongrel dogs. Using the activated coagulation time test, a dose response relationship and half-life for heparin action were determined in each dog. It was observed that a heparin dose of 200 units/kg provided less than the generally accepted minimal anticoagulant effect of an activated coagulation time of 180 seconds, while a dose of 500 units/kg produced adequate anticoagulation. Even then, the half-life of heparin activity was less than 50 minutes. These findings suggest that even when large doses of heparin are utilized to provide adequate initial anticoagulation, the short half-life in dogs makes frequent assessment of the heparin response essential. The activated coagulation time test provided a rapid and simple determination of heparin activity within each individual and was used to insure adequate anticoagulation.

Animals↗
PubMed1983

Predictions of blood flow from thermal clearance during regional hyperthermia.

In order to provide a method for estimation of regional blood flow during hyperthermia, a mathematical model has been developed which employs thermal clearance to measure this physiologic parameter. Limbs of mongrel dogs were heated with 2450 megaHertz microwaves to temperatures of 43 degrees C, 45 degrees C, or 47 degrees C and thermal washout was measured at five minute intervals throughout each treatment period. Calculated blood flow indicates that in response to heat challenge, normal tissue compensates by increasing regional blood flow within the treatment volume. This increase in blood flow continues to a maximum value after which the blood flow begins to decrease. Data indicate that the time for maximum increase in blood flow (induction time) decreases as treatment temperature increases. These induction times were 40 minutes, 25 minutes, and 15 minutes for treatment temperatures of 43 degrees, 45 degrees, and 47 degrees C, respectively. The data also show that the calculated value of peak blood flow is directly related to treatment temperature. Calculated peak blood flow values reached 37.8, 59.0, and 183.0 ml/minute/100 grams of tissue during 43 degrees, 45 degrees, and 47 degrees C, hyperthermia, respectively. It is suggested that a therapeutic advantage could be gained by treating tumors for a specific length of time during which the blood flow in adjacent normal tissues continues to increase. This would take maximum advantage of normal tissue's ability to compensate for increased temperature, and would exploit any decreased ability of tumor tissue to perform this same function.

Animals↗
PubMed1981

Suppression of acute and chronic inflammation by orally administered prostaglandins.

Oral administration of a stable analog of prostaglandin E1 (PGE1) 15-(S)-15-methyl-prostaglandin E1, can suppress both chronic adjuvant-induced polyarthritis and acute immune complex-induced vasculitis in a dose dependent manner. Histopathologic studies of tibiotarsal joints from rats with adjuvant disease showed suppression of arthritis in animals treated with the PGE1 analog from time of adjuvant challenge. This study represents the first demonstration of suppressed experimental polyarthritis by an orally administered prostaglandin. Suppression of the acute immune complex-induced vasculitis was demonstrated using 15- methyl-PGE1 administered orally 12 hours prior to antigen-antibody challenge. Diminution of tissue injury resulting from immune complex-induced vasculitis is reflected by a decrease in vaso-permeability, indicating suppressed vascular damage in animals treated with prostaglandin. These studies demonstrate the potential use of orally active prostaglandins as an antiinflammatory agent.

Administration, Oral↗