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Biomedical subjects

R P Custer

Publications and source records attributed to R P Custer.

At least 37 records · Page 2Linked to original sources
PubMed1981

Enhancement of squamous cell development in cultured skin by cyclic adenine nucleotide and prostaglandins.

The present study tests the hypothesis that agents known to elevate the level of intracellular cyclic adenine nucleotide may direct different epithelial cells onto a pathway of epidermoid (squamous) development and differentiation. We report here that the mixture of dibutyryl cyclic AMP (dbcAMP), prostaglandins E1, E2 and B1 (PG E1, E2, B1), and papaverine (pap) enhances the rate of normal squamous cell development in organ-cultured skin of chick embryos. The three components may act synergistically to elevate the level of intracellular cyclic adenine nucleotide. We recently reported that the same group of agents induces abnormal development (squamous metaplasia) and aberrant differentiation (keratin production) in the normally cuboidal epithelium of cultured whole mammary glands of mice [1]. Thus, dbcAMP, PG E1, E2, B1, and pap are effective in enhancing normal squamous cell development and also in inducing squamous metaplasia de novo in the epithelial components of two different organs of embryonic and adult animals of two classes of vertebrates. The combined findings are suggestive that cyclic adenine nucleotide together with the prostaglandins may act generally on diverse types of epithelia to bring about squamous cell development and a differentiation marked by keratin production.

Aldosterone↗
PubMed1980

The Icr:Ha(ICR) mouse: a current account of breeding, mutations, diseases and mortality.

This stock of albino mice is minimally inbred (0.5% per generation), and has been rigidly selected for fecundity. It is widely employed in oncological and pharmaceutical research. Spontaneous tumours arose in 55% of animals, multiple in 28%, averaging 1.66 per mouse. Females developed tumours at an earlier age than males. Predominant tumour types were pulmonary (23.1%), lymphoreticular (20%), and mammary (14%--23% of females). Miscellaneous tumour types (42.9%) ranged in frequency from 0.2 to 2.0%, the latter being hepatomas. Distribution of mammary tumours indicated that milk-borne mammary tumour virus was absent. Non-neoplastic disease was present in 58.6%, 24.1% being pulmonary and predominant in the young, while renal (31.2%) and cardiovascular (10.2%) disease was common in the elderly. Males outlived females.

Aging↗
PubMed1979

Retinoid prevents mammary gland transformation by carcinogenic hydrocarbon in whole-organ culture.

The mouse mammary gland in whole-organ culture, an in vitro system that is capable of alveolar development, differentiation, involution, and oncogenic transformation, has been used to examine the effects of the retinoid 2-retinylidene-5,5-dimethyl-1,3-cyclohexanedione (retinylidene dimedone) on epithelial transformation by a low concentration (10 nM) of the carcinogen 7,12-dimethylbenz[a]anthracene. The retinoid significantly prevented mammary gland transformation only when administered after the carcinogen. In addition, the phenotypes of the early transformed state of the mammary gland were suppressed for 20 days after removal of the retinoid. The retinoid was effective during both mammary alveolar development and regression in culture at concentrations as low as 1 nM, and itself had no significant transforming or cytotoxic activity. Mammary glands treated with both the carcinogen and the retinoid resembled, at the microscopic level, those given the solvent (dimethyl sulfoxide) only. The mouse mammary gland in whole-organ culture provides a promising model system in which to study the actions by which retinoids prevent and suppress the chemical transformation in vitro and oncogenesis in vivo of epithelial cells in general and of mammary gland in particular. The present findings support the suggestion that a search for suitable retinoids as chemopreventive agents against human breast cancer is warranted. This model system may be useful as initial indicator in that search.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Effects of ultraviolet light on nude mice: cutaneous carcinogenesis and possible leukemogenesis.

Squamous cell carcinomas were induced by ultraviolet irradiation in the skin of all T-cell deficient nude mice rendered sufficiently long-lived by reconstitution with syngeneic splenic or thymic cells. All homozygous hairless mice similarly exposed developed squamous cell carcinomas. Striking granulocytic proliferation was provoked in one hairless and in five reconstituted nude mice; two of the latter were interpreted as having true granulocytic leukemia.

Animals↗
PubMed1978

Somatic cell origin of teratocarcinomas.

Malignant teratocarcinomas arise from developmentally totipotent normal stem cells. Whether the targets are embryonal somatic cells or germinal cells has long been a matter of controversy. Past experiments on teratocarcinoma induction by ectopic grafting of early rodent embryos or fetal germinal ridges have remained ambiguous because embryos ordinarily soon form germ cells, and parthenogenetic germ cells form "embryos." In order to interrupt the developmental cycle at its most telling point, day 6 (egg-cylinder stage) mouse embryos of genetically sterile types were grafted; in such grafts, only a terminal residue of totipotent embryonal somatic ("ectoderm") cells is available, and subsequent germ cell development is severely impaired. One graft series, from S1(J)/+ matings, comprised 25% S1(J)/S1(J) presumptive sterile embryos; these grafts formed tumors containing embryonal carcinoma cells as often (47%) as did control +/+ grafts (41%) on the same genetic background. In another series, from W/+ matings, tumors of the sterile W/W genotype were individually identified by means of a closely linked marker, phosphoglucomutase (PGM, EC 2.7.5.1; Pgm-1 locus), coding for electrophoretic enzyme variants and incorporated into the stock. Four tumors were obtained (out of 16) that had the PGM-1D phenotype diagnostic for W/W, and that also contained embryonal carcinoma cells. Therefore, the malignancy arises here in susceptible somatic embryonal stem cells at the terminal stage of their capacity for totipotency. Other teratocarcinomas-whether induced or spontaneous-of ostensible germ-cell origin by parthenogenesis may also depend upon development of the same somatic target cells before neoplastic conversion can occur. A general model based on these experiments is proposed for all malignancies: Malignant transformation of a particular kind of normal stem cell may be possible only when that stem cell has progressed to the threshold of further differentiation.

Animals↗
PubMed1978

Dystrophic cardiac calcinosis in mice: genetic, hormonal, and dietary influences.

Mice of five inbred strains (BALB/c, C3H, C3Hf, DBA/2, and C57BL/6) of both sexes, mated and virginal, were examined for the incidence, severity, and location of dystrophic cardiac calcinosis (DCC) at various ages. Three hybrids, B6C3F1, C3B6F1, and CC3F1 of both sexes, all mated, were likewise studied. Excepting DBA/2, females of the inbred strains acquired the lesion at a much earlier age than males; DCC appeared in young DBA/s mice of both sexes. DCC in BALB/c mice was almost exclusively epicardial and occurred with equal frequency and severity in mated males and females, with higher incidence but lesser extent in virginal females. The occurrence was highest, the degree most severe, and the location exclusively myocardial in C3H and C3Hf mated females, irrespective of parity, whereas virginal females of these strains were entirely free of disease even after administration of exogenous progesterone. Involvement of males, also myocardial, was relatively minimal, especially in C3Hf mice. Over half the DBA/2 mice were affected, regardless of sex or mating; calcinosis appeared in the epicardium and/or myocardium, predominantly in the myocardium. Strain C57BL/6 was completely devoid of the lesion, as were the two hybrids thereof, B6C3F1 and C3B6F1. The hybrid of BALB/c and C3H showed a high incidence of minimal involvement, exclusively myocardial and limited to breeding females, indicating dominance of the C3H gene(s). Renal calcinosis was uncommon among BALB/c mice but was frequently found in C3H, C3Hf, and DBA/2 strains. Pulmonary calcinosis was rare and limited to C3H and C3Hf female breeders. Mated C3H females fed increasing amounts of fat showed a concomitant rise in incidence and severity of the cardiac lesions. Progression of the lesion from necrotic myocardial fibers to fibrocalcific masses is illustrated, as is formation of the renal deposits.

Aging↗
PubMed1977

Hepatotoxicity in Wistar rats following chronic methotrexate administration: a model of human reaction.

The effects of ip administration of methotrexate (MTX) on 3-month-old male Wistar rats were studied. We administered log doses from 125 to 2,000 mug/kg, five times per week for as long as 24 months. The massive doses were promptly lethal, and most rats receiving 500 mug or more/kg died within a few weeks. Severe hematopolietic depression and ulcerative gastrointestinal lesions were observed. Truly chronic intoxication was achieved with the lesser doses. Rats in this category developed serious liver damage, namely, varying degrees of fatty metamorphosis, necrosis, atrophy of hepatic cords, and fibrosis. Hematopoietic depletion occurred in the spleen and bone marrow. Hemosiderosis was prominent in the spleen and liver. Pulmonary lesions--chiefly emphysema, occasionally fibrosis--were found less consistently. These studies demonstrated the ability of MTX to induce lesions, most consistently hepatic, in the Wistar rat, and thus have provided an animal model to evaluate protective measures.

Age Factors↗
PubMed1977

Chronic toxicity of methotrexate in rats: partial to complete projection of the liver by choline: Brief communication.

Methotrexate (MTX) inhibits the enzyme dihydrofolate reductase, which in turn limits the body's ability to perform transmethylation reactions. This study examined the hypothesis that the consequent deficiency of an important methylated compound, choline, may have contributed to the MTX-induced fatty change in the liver of W rats. Groups of rats were given MTX alone or MTX plus choline in varying dose combinations. All groups but one receiving the combined treatment showed a significantly lower triglyceride concentration in their livers and much less visible hepatocytic fat on histologic examination than did those given MTX alone. The protective effect of choline on the liver was dose related, the unaffected group having received a very small amount. Growth rate, survival, and hematopoietic depression due to MTX were unaltered by choline administration.

Animals↗
PubMed1976

Metastatic melanoma of the maxilla presenting as a gingival swelling.

Malignant melanoma metastatic to the gingiva has been reported only once. We present a case in which the occurrence of melanoma in the gingiva followed extraction of a periapically "abscessed" tooth. Since the initial periapical mass may well have been a metastatic tumor, particularly in a patient undergoing therapy for disseminated malignant disease, the need for biopsy of such lesions is emphasized.

Adult↗
PubMed1976

Influence of regenerative capacity and innervation on oncogenesis in the adult frog (Rana pipiens).

Twenty-two sarcomas were induced in 19 adult frogs (Rana pipiens) treated with 3-methylcholanthrene pellets. Thirteen of these tumors arose first in a denervated forelimb, and only 2 arose first in normal or nerve-supplemented control forelimbs (P = 0.004). The remaining tumors developed either as a second tumor in a tumor-bearing frog or in hindlimbs. The critical role of innervation in regenerative capacity suggests that the predilection to tumor formation in the denervated limbs may have resulted from their lessened regenerative capacity.

Animals↗
PubMed1976

Invasion and metastasis of a xenogeneic tumor in nude mice.

When aliquots of a malignant hamster tumor were transplanted to nude mice and to hamsters, the tumor showed 1) more rapid growth in the hamster, 2) local invasion and metastasis in both species, and 3) occasional spontaneous regression in the nude mouse.

Animals↗
PubMed1976

Differentiation of a methylcholanthrene-induced sarcoma to a benign plexiform fibroneural tumor in an adult frog (Rana pipiens). Possible influence of host regenerative capacity.

A spindle cell sarcoma appeared 20 months after implantation of a pellet of 3-methylcholanthrene in the denervated foreleg of an adult frog, Rana pipiens. Its growth rate and cellular structure were observed over the subsequent 19 months, the former remaining constant for the first 14 months, then slackening markedly during the final 4 months. Serial biopsies disclosed maturation to a well-differentiated fibroneural tumor of benign appearance, the change taking place notably during the period of decelerated growth rate. An autotransplant of the tumor to the hind leg adopted the same growth pattern and maturation. Possible causes for this behavior are discussed.

Animals↗
PubMed1975

Growth of human normal and neoplastic mammary tissues in the cleared mammary fat pad of the nude mouse.

Dysplastic and malignant human breast tissues were grown successfully in the cleared mammary fat pads (CFP) of nude mice. The mammary fat pads were cleared while the mice were in a germfree isolator. Prepared mice were removed fron the germfree enviornment to facilitate transplantation of the human mammary tissue into their CFP and subsequently were maintained in sterile laminar flow racks.

Animals↗