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Biomedical subjects

D Nagel

Publications and source records attributed to D Nagel.

At least 91 records · Page 5Linked to original sources
PubMed1982

Gastric tumorigenesis by a single dose of 4-(hydroxymethyl)benzenediazonium ion of Agaricus bisporus.

4-(Hydroxymethyl-benzenediazonium tetrafluoroborate was administered as a single intragastric instillation at 400 micrograms/g to Swiss albino mice. The treatment gave rise to glandular stomach tumours in incidences of 30% in females and 32% in males. Histopathologically, the tumours were classified as polypoid adenomas and adenocarcinomas. This diazonium ion is an ingredient of the cultivated mushroom of commerce, Agaricus bisporus. The implications are self-evident.

Adenocarcinoma↗
PubMed1982

1,2-diallylhydrazine dihydrochloride carcinogenesis in mice.

Continuous administration of 0.0625% 1,2-diallylhydrazine dihydrochloride in drinking water for life to 6-week-old randomly bred to Swiss mice induced lung tumors. In comparison with the untreated controls, the lung tumor incidence rose from 25 to 80% in the females and from 26 to 80% in the males. The treatment had no apparent effect on the development of other tumor types. Histopathologically, the lesions were classified as adenomas and adenocarcinomas of the lungs. The work is a continuation of our structure activity inquiry concerning the relative carcinogenic potencies of the dialkyl versus the monoalkyl series of hydrazine analogues.

Adenocarcinoma↗
PubMed1982

Neurotic depression: results and cluster analyses.

On a sample of 193 former depressive inpatients (145 female, 53 male), cluster analyses were carried out, both on the subjects and on the items for classficatory reasons. The study was based on 38 items relevant for the diagnostic axes of clinical phenomenology (during illness), characteristics of the course, and (intermorbid) personality. The findings from the multivariate statistical methods support the existence of a neurotic depressive disorder which can be identified by essential features and accessory features on the aforementioned three diagnostic axes. Especially noteworthy are maintained reactivity to the outside world, normal sadness, hypochondriasis, and open aggression; insidious onset of the depressive episode and long duration; and the neurotic basic personality. Despite a certain heterogeneity of the isolated neurotic depressive subgroups and profiles, their similarity is based on substantial common properties. In a comprehensive view of our findings, one can justifiably speak of a specific disorder that need not be defined in the negative as compared to the endogenous depression, but can be characterized in the positive.

Aggression↗
PubMed1981

Current knowledge of pancreatic carcinogenesis in the hamster and its relevance to the human disease.

Syrian hamsters present a unique species for induction of pancreatic tumors that in many aspects resemble human pancreatic cancer. The specific response of Syrian hamsters, in contrast to may other rodents, for development of pancreatic ductal (ductular) tumors is not yet known. All pancreatic carcinogens thus far tested show certain common features. They are all nitrosamines that possess or can be metabolized to compounds with 2-oxopropyl- or 2-hydroxypropyl substituents. All but one, N-nitroso-methyl(2-oxopropyl)amine, occur or metabolize to nitrosamines with the ability to cyclize and form structures resembling glucose. Hence it is suggested that this cyclic structure may be responsible for the pancreatic carcinogenicity of these nitrosamines, as has been proposed for the pancreatotropic effect of streptozotocin. It is also of further interest that one pancreatic ductal (ductular) carcinogen, N-nitroso-2-methoxy-2,6-dimethylmorpholine, which possesses a totally cyclic structure, acts, like streptozotocin, as beta-cell cytotoxic and diabetogenic when given in a high single dose. Modification of pancreatic tumor induction has been demonstrated by specific procedures. A high fat diet significantly increases both the incidence and number of induced cancers. Methods for early diagnosis and therapy are being developed and their significance and applicabilities for clinical use will be of major importance. Compared with the other most common types of human cancer, pancreatic cancer has extraordinary characteristics, which make the disease one of the most mysterious of maladies. Consequently, pancreatic cancer represents a serious international problem and requires urgent resolution, especially with regard to its etiology, early diagnosis, prevention, and therapy.

Animals↗
PubMed1981

The effect of N-nitroso-2-methoxy-2,6-dimethylmorpholine on endocrine and exocrine pancreas of Syrian hamsters.

N-Nitroso-2-methoxy-2,6-dimethylmorpholine (MeNDMM), a cyclic derivative of the proposed proximate pancreatic carcinogen N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP), is shown to have an almost selective cytotoxic effect on pancreatic beta-cells when a single high dose is given to Syrian hamsters. Hence in this aspect its effect is comparable to that of streptozotocin, which has a glucose moiety similar to the MeNDMM structure. However, contrary to the effect of streptozotocin, low single (subdiabetogenic) doses of MeNDMM led to the development of pancreatic ductular and mixed ductular-insular neoplasms; only 1 animal also had islet cell adenoma. It therefore seems that MeNDMM possesses an affinity for both endocrine and exocrine pancreatic tissue. Other target tissues of MeNDMM were the forestomach, intra- and extrahepatic bile ducts, liver, kidneys and vagina. The tumors of these organs appeared in various incidences, partially in relation to dose and/or survival time. The possible mechanisms of the MeNDMM effect upon the endocrine and the exocrine pancreas is discussed.

Adenoma↗
PubMed1981

Methylation of hamster DNA by the carcinogen N-nitroso-bis (2-oxopropyl)amine.

The alkylation of hamster liver, lung and pancreas DNA by [1-14C]- and [2,3-14C]N-nitrosobis (2-oxopropyl) amine (BOP) has been examined. The specific activity of pancreas DNA after [2,3-14C]BOP administration was only 2% of that when [1-14C]BOP was given. 7-Methylguanine, but not O-6-methylguanine, was found in hydrolysates of liver and pancreas DNA. Nearly equal amount of alkylation were produced in the liver when [1-14C]- and [2,3-14C]BOP were given. At least one-half of the radioactivity in the liver was associated with N-alkylated purines, whereas only 20% was in this form in the pancreas.

Animals↗
PubMed1981

Carcinogenic effects of 1,1-di-n-butylhydrazine in mice.

Lifetime administration of 0.03125% 1,1-di-n-butylhydrazine in drinking water to Swiss mice, from 6 weeks of age, induced tumors of the lungs, forestomach and liver. The tumor incidences in these tissues in untreated controls were 25, 2 and 0.5%, whereas in the treated groups the corresponding tumor incidences increased to 68, 39 and 5%, respectively. Histopathologically these lesions were classified as adenomas and adenocarcinomas of the lungs, squamous cell papillomas and carcinomas of the forestomach, and benign hepatomas and liver cell carcinomas. The work is part of a structure activity inquiry and its specific aim is to disclose whether the dialkyl derivatives of hydrazine are more active carcinogens than the monoalkyl analogues.

Animals↗
PubMed1981

Identification of the endogenous depressive syndrome based on the symptoms and the characteristics of the course.

Using a sample of 198 depressed patients (145 female, 53 male) retrospective histories of the illnesses were collected during a depression-free interval, based on a catalogue containing 38 symptom items and the course of the depression (including the interval personality). A cluster analysis on persons and items filtered out an endogenous depressive item profile, corresponding with the clinical syndrome of patients diagnosed as endogenous depressives in the clinics, although determined without reference to the clinical diagnoses. Our study supports many results from earlier multivariate statistical studies. We consider our data to be an essential contribution towards the establishment of a multiaxial clinical picture.

Adult↗
PubMed1981

Attempted tumor induction with agaritine in mice.

Agaritine, a constituent of the cultivated mushroom of commerce Agaricus bisporus, was administered at concentrations of 0.0625 and 0.03125% in drinking water daily for life to randomly bred Swiss mice. Consumption of the chemical resulted in no detectable carcinogenic action under the experimental conditions. During the course of the experiment, however, a substantial number of animals developed convulsive seizures.

Adenocarcinoma↗
PubMed1981

Tumorigenesis with 1,1-diallylhydrazine in mice.

1,1-Diallylhydrazine was administered as a 0.03125% solution in drinking water for life to Swiss mice, from 6 weeks of age. Compared to untreated controls, in treated animals the lung tumor incidence rose from 25 to 76% in females and from 26 to 76% in males, whereas the incidence of forestomach tumors increased from 4 to 14% in females and from 0 to 34% in males. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of the lungs and squamous cell papillomas and carcinomas of the forestomach. This work is part of our structure activity inquiry and demonstrates the relative carcinogenic potency of another disubstituted allylhydrazine.

Adenocarcinoma↗
PubMed1980

Induction of local epidermal papillomas and carcinoma by selected nitrosamines.

Weekly cutaneous application of N-nitrosobis (2-oxopropyl)amine (BOP) at a dose of 2 mg/application to the neck area resulted in the induction of local papillomas and carcinomas in 80% of Syrian hamsters as early as 19 weeks post-treatment. In addition, a few tumors of internal organs (predominantly in the liver) were also found. N-Nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP), a common metabolite of BOP and BHP, was also found to be an epidermal carcinogen at a dose of 3.8 mg/application. N-Nitrosobis(2-hydroxypropyl)amine (BHP), however, failed to induce any epidermal lesions, when applied similarly at a much higher dose level (%) mg/animal/week). In contrast to BOP and HPOP, BHP induced a high incidence of tumors in internal organs, especially pancreatic cancer, which was the only induced tumor in 5 animals. Skin absorption studies demonstrated that BHP, but not BOP is rapidly absorbed and was detectable in the blood in concentrations of up to 5.5 mug/ml as early as 15 min after carcinogen administration. The possible reasons for the differing effects of BHP and BOP upon hamster skin are discussed.

Adenocarcinoma↗
PubMed1980

Tumorigenesis by N-n-propyl-N-formylhydrazine in mice.

Continuous administration of 0.04% N-n-propyl-N-formylhydrazine (PFH) for life in drinking water to 6-week-old randomly bred Swiss mice induced tumours of the lungs, preputial glands, liver and gallbladder. The tumour incidences in these 4 tissues were 91, 22, 8 and 6%, whereas in the untreated controls they were 25, 0, 0.5 and 0.5%, respectively. The higher dose of 0.08% PFH, given under identical conditions, induced only tumours of the lungs, liver and gall bladder in low incidences, since the compound was too toxic for the mice. Histopathologically, the tumours were classified as adenomas and adenocarcinomas of the lungs, squamous-cell papillomas, and carcinomas and fibrosarcoma of preputial glands, benign hepatomas and liver-cell carcinoma, as well as adenomas and adenocarcinoma of the gall bladder. The investigation is part of our structure/activity relationship inquiry aimed at revealing the mechanism of action of the N-alkyl-N-formylhydrazine series of chemicals.

Animals↗
PubMed1980

Tumorigenic action of N-n-butyl-N-formylhydrazine in mice.

Continuous administration of 0.04% N-n-butyl-N-formylhydrazine (BFH) in drinking water to 6-week-old randomly bred Swiss mice for life produced tumors of the lungs, preputial and clitoral glands. The tumor incidences in these three tissues of the treated animals were 87, 66, and 10%, whereas in the untreated controls they were 25, 0, and 0%, respectively. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of the lungs, squamous cell papillomas and carcinomas, angio-, fibro-, and myxo- sarcomas of preputial glands and squamous cell papillomas and carcinomas of clitoral glands. N-n-Butyl-N-formylhydrazine is a structural homologue of the carcinogenic N-methyl-N-formylhydrazine and N-ethyl-N-formylhydrazine. These studies are integral parts of structure activity relationship inquiries.

Animals↗