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Biomedical subjects

J Farmer

Publications and source records attributed to J Farmer.

At least 73 records · Page 4Linked to original sources

Is delayed neurotoxicity a property of all organophosphorus compounds? A study with a model compound: parathion.

A recently reported hypothesis of other investigators that the induction of delayed neurotoxicity is a property of all organophosphorus compounds including parathion was evaluated in light of the inability of parathion to induce in our laboratory any clinical, histological, or biochemical signs of delayed neurotoxicity in hens following a very intensive dosing regimen. Parathion was administered orally or applied dermally as 1 mg/kg/day for 1 week and then the dose was increased by 1 mg/kg/day at weekly intervals up to 6 mg/kg/day which was given thereafter until a total of 90 doses. Results indicate that parathion either orally or dermally did not produce delayed neurotoxicity in hens comparable to that induced by tri-orthocresyl phosphate (TOCP) in this experiment. This finding is supported by clinical, histological, and biochemical evidences. No clinical signs or histopathological changes in spinal cords and sciatic nerves of the type associated with delayed neurotoxicity were observed in any of the surviving parathion-treated hens. Moreover, this extensive treatment with parathion resulted in no significant in vivo effect on neurotoxic esterase, an esterase believed to be the initial target in the genesis of delayed neurotoxicity. These results agree with the general hypothesis that delayed neurotoxicity is a special toxic effect of some but not all of the organophosphorus esters.

Acetylcholinesterase↗

Species susceptibility to delayed toxic neuropathy in relation to in vivo inhibition of neurotoxic esterase by neurotoxic organophosphorus esters.

Tri-o-cresyl phosphate (TOCP) and O-ethyl O-(4-cyanophenyl) phenylphosphonothioate (cyanofenphos, Surecide) were found to be delayed neurotoxicants. They were administered to chickens by gavage at 100 and 30 mg/kg . d for 15 d, respectively. In CD-1 mice neither TOCP nor cyanophenphos induced any of the usually recognized clinical symptoms of neuropathy when administered daily by gavage at 262 or 31.25 mg/kg . d for 30 d, respectively. In the chickens, TOCP and cyanofenphos produced about 98 and 90% in vivo inhibition of brain neurotoxic esterase (NTE) activity. In the mice, 24 h after the last daily dose, TOCP and cyanofenphos produced only about 50 and 40% in vivo inhibition of the brain NTE activity. Parathion [O,O-diethyl O-(4-nitrophenyl) phosphorothioate], at 2 or 6.75 mg/kg . d for 15 or 30 d, did not induce neuropathy in either chicken or mice and produced no significant in vivo inhibition of brain NTE activity at the end of the dosing regimen. The specific activity of NTE in control chicken brain crude homogenate was much higher than that in mouse brain homogenate. These results suggest that the differences between chickens and mice in susceptibility to neurotoxic organophosphates may be attributed to (1) inhibitor specificity of NTE forms in the brain in these two different animal species and/or (2) inability of the active metabolites of these neurotoxic compounds to reach the site of action.

Animals↗

The formation and orientation of brush border vesicles from rat duodenal mucosa.

An electron-microscopic study of various fractions taken during a newly developed method for preparation of brush border vesicles from rat duodenum, has shown that vesiculation of microvilli can occur in situ on the brush border membrane. This mode of formation ensures that the vesicle membranes are oriented as in vivo and that they are "right-side-out". The disruption of core protein-fibres appears to be a prerequisite for vesicle formation.

Animals↗

Neoplastic and preneoplastic lesions induced in female C3H mice by diets containing diethylstilbestrol or 17 beta-estradiol.

To study the long term effects of estrogenic diets, 2160 virgin female C3H/Hel mice, having a high titer to the mammary tumor virus factor (MMTV), were fed diets containing 0, 10, 100, 500, or 1000 ppb diethylstilbestrol (DES) or 100, 1000, or 5000 ppb 17 beta-estradiol (E2) from 6 to 110 weeks of age; 1368 virgin female C3HeB/FeJ mice, having a low titer to the MMTV, were fed diets containing 0, 10, 1000, or 500 ppb DES from 6 to 136 weeks. In estrogen-treated mice, the incidence of cervical adenosis and of mammary hyperplastic alveolar nodules was increased and the time to development of mammary adenocarcinomas was shortened. These changes tended to increase with dose and time and appeared earlier in the C3H/HeJ mice. Other tumors observed included 32 cervical and 20 endometrial adenocarcinomas, 16 cervical granular cell myoblastomas, 12 peritoneal mesotheliomas involving the uterus, 2 cervical and 4 vaginal squamous cell carcinomas, 2 ovarian teratomas, 6 osteosarcomas, 25 pheochromocytomas and 3 thyroid carcinomas. Of these tumors, 1 cervical and 2 endometrial adenocarcinomas, and 4 pheochromocytomas occurred in C3HeB/FeJ control mice at 104-130 weeks; none occurred in C3H/HeJ controls. This study indicates that the MMTV facilitates the development of mammary lesions in C3H mice, that estrogens predispose C3H mice to endometrial and cervical adenocarcinomas, and that cervical adenosis may be a precursor of cervical adenocarcinoma in C3H mice and serve as an early indicator of the potential uterine carcinogenicity of a test compound. It supports the view that the C3H mouse may serve as an animal model for uterine adenocarcinomas and adenosis in women exposed to estrogens.

Animals↗

Dose-response hyperplasia and neoplasia from feeding N-2-fluorenylacetamide (2-FAA) to BALB/c mice for varying time intervals.

Hyperplasia induced by N-2-fluorenylacetamide requires the continuous presence of the chemical for its maintenance. Feeding the chemical at levels of 8 to 86 ppm results in a dose-response related urinary bladder hyperplasia and, after 9 to 12 months, in bladder neoplasia at the higher dose levels. Neoplasia of the lungs, liver, parotid gland, lacrimal gland, harderian gland, and submaxillary gland was also observed. Measurement of oncogenic viruses revealed no synergism with 2-FAA and no relationship between virus counts and neoplasia. Calcareous pericarditis was observed and most general toxicological effects occurred in the liver. A pronounced sex difference in response was observed with the males giving greater responses than the females in all instances.

2-Acetylaminofluorene↗

The role of proctoring in personalized instruction.

The effect of amount of student-proctor interaction was investigated within the framework of Keller's (1968) method of personalized instruction. College students enrolled in introductory psychology were randomly assigned to five groups: 0%, 25%, 50%, 75%, and 100%, reflecting the percentage of units on which each student was proctored. The results indicated that (a) the proctored students were superior to the non-proctored students as measured by final examination performance, (b) for the proctored groups, the amount of proctoring did not differentially affect final examination performance, and (c) the major effect of increased proctoring was an acceleration of the rate of progress through the course.

Journal Article↗

Varying temporal placement of an added stimulus in a fixed-interval schedule.

One paradigm for exploring stimulus effects on behavior is defined for steady state experiments. The paradigm is illustrated by a 60-sec fixed-interval reinforcement schedule wherein a 6-sec light is introduced into each interval. The temporal relation of this stimulus to the reinforcer is the independent variable that is systematically explored. Two experiments studied this temporal relation under two parametric conditions: (a) when the 6-sec light occurs once in each 60-sec interval, (b) when the 6-sec light occurs twice in each interval, the second time always during the 6 sec immediately preceding the reinforcer. Functions are presented showing the effect of the 6-sec light on responding at all points in the fixed-interval.

Animals↗

Bulimia and interpersonal relationships: an extension of a longitudinal study.

We examined changes in bulimia in female college students and changes in the relationship between bulimia and satisfaction with interpersonal relationships. We extended data collected from a 19-month time period in a previous study to a 31-month time period. Bulimics, subclinical bulimics, and normals showed a leveling off of the previous decline in bulimic symptoms assessed at the 19-month testing. There were strong negative correlations between the Bulimia Test and ratings of satisfaction with male interpersonal relationships, but the correlations were not significant for satisfaction with female relationships.

Adolescent↗

A comparison of statistical methods for low dose extrapolation utilizing time-to-tumor data.

The assessment of health risks due to low levels of exposure to potential environmental hazards based on the results of toxicological experiments necessarily involves extrapolation of results obtained at relatively high doses to the low dose region of interest. In this paper, different statistical extrapolation procedures which take into account both time-to-response and the presence of competing risks are compared using a large simulated data base. The study was designed to cover a range of plausible dose response models as well as to assess the effects of competing risks, background response, latency and experimental design on the performance of the different extrapolation procedures. It was found that point estimates of risk in the low dose region may differ from the actual risk by a factor of 1000 or more in certain situations, even when precise information on the time of occurrence of the particular lesion of interest is available. Although linearized upper confidence limits on risk can be highly conservative when the underlying dose response curve is sublinear in the low dose region, they were found not to exceed the actual risk in the low dose region by more than a factor of 10 in those cases where the underlying dose response curve was linear at low doses.

Animals↗

Nonneoplastic changes induced in female C3H mice by chronic exposure to diethylstilbestrol or 17 beta-estradiol.

The long-term nonneoplastic effects of estrogenic diets were studied in female C3H/HeJ and C3HeB/FeJ mice. C3H/HeJ mice received diets containing 0, 10, 100, or 500 ppb diethylstilbestrol (DES) or 100, 1000, or 5000 ppb 17 beta-estradiol (E2) from 6 to 110 wk of age. C3HeB/FeJ females were fed diets containing nominal concentrations of 0, 10, 100, or 500 ppb DES from 6 to 136 wk of age. Responses of both strains to DES were qualitatively identical. Histological changes in the reproductive tract induced or increased by DES in both strains and by E2 in C3H/HeJ mice included stromal mucoid changes in the vagina and cervix, epithelial keratinization in the vagina, and glandular hyperplasia in the uterine horns. Increasing doses above 10 ppb DES or 100 ppb E2 increased the prevalence and, in some cases, severity of these responses. Dose-responses to DES for these endpoints were virtually indistinguishable in the two strains. At 10 ppb DES or 100 ppb E2 there were minimal or no observable effects. When the nonneoplastic dose-response data were compared with neoplastic dose-response data previously reported, no consistent relation between doses causing neoplastic and nonneoplastic responses was seen for the two estrogens.

Animals↗

Adjunctive hyperbaric oxygen for treatment of rhinocerebral mucormycosis.

The therapy of rhinocerebral mucormycosis includes aggressive surgical debridement, administration of high-dose amphotericin B, and control of underlying predisposing conditions, especially diabetes and immunosuppression or immunodeficiency. Hyperbaric oxygen suppresses fungal growth in vitro and has theoretical value in treating mucormycosis because it reduces the tissue hypoxia and acidosis that accompany vascular invasion by the fungus. In a retrospective review of patients at Duke University Medical Center with rhinocerebral mucormycosis, six patients were treated with hyperbaric oxygen and seven cases (involving six patients) were treated without hyperbaric oxygen. All patients received surgical debridement and amphotericin B. Two of six patients receiving hyperbaric oxygen therapy died, and four of seven patients not receiving hyperbaric oxygen therapy died. Adverse effects from hyperbaric oxygen were minimal. Because mucormycosis occurs infrequently, this retrospective review involved a small number of patients. Despite this limitation, adjunctive hyperbaric oxygen appears to be a promising clinical modality for the treatment of rhinocerebral mucormycosis and warrants further investigation.

Adolescent↗