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Biomedical subjects

R H Adamson

Publications and source records attributed to R H Adamson.

At least 109 records · Page 6Linked to original sources
PubMed1976

Carcinogenicity of aflatoxin B1 in rhesus monkeys: two additional cases of primary liver cancer.

Three of 42 (7%) monkeys given aflatoxin B1 (AFB1) for longer than 2 years have developed primary malignant neoplasms of the liver. Liver biopsies performed at intervals during aflatoxin administration revealed that neoplasia was preceded by pathologic lesions of the liver, including toxic hepatitis, proliferation of pseudotubules, and hyperplastic nodules. Serum alpha-fetoprotein levels, monitored in one of the monkeys by radioimmunoassay, paralleled tumor growth and recurrence of the hepatocellular carcinoma. Normal serum alpha-fetoprotein levels were noted for a monkey with hemangioendothelial sarcoma. Our results implicate AFB1 as a liver carcinogen in monkeys and add additional support to the hypothesis that humans exposed to this substance may be at risk of developing liver cancer.

Aflatoxins↗
PubMed1976

Intravenous hepatosplenography. Experiment evaluation of a new contrast material.

A new, lipoid-based experimental contrast material (AG 60-99) was intravenously infused into 29 rhesus monkeys. The injections resulted in dense hepatosplenograms, preserving diagnostic quality for over 24 hours, and enabling routine utilization of tomography. This technique is capable of demonstrating simulated hepatic masses as small as 5 mm in diameter in vivo. Limited histopathologic and toxicity studies showed no serious or lasting toxic manifestations from AG 60-99 and none of the animals died from it. AG 60-99 is felt to be potentially useful in the radiographic detection of early metastic or lymphomatous involvement of the liver and spleen.

Animals↗
PubMed1976

Serum sialic acid levels in lung cancer patients.

The levels of N-acetyl neuraminic acid (sialic acid) in normal men and pre-and post-menopausal women were determined. Smoking post-menopausal estrogen therapy, oral contraceptives, and refreezing had no effects on sialic acid levels. Pre-treatment values from patients with lung carcinoma showed markedly elevated levels of sialic acid (0.697 +/- 0.149 muM/ml) as compared to those from normal controls (0.432 +/- 0.067 muM/ml). The potential usefulness of sialic acid as a biological marker is discussed.

Adenocarcinoma↗
PubMed1976

The disposition of coralyne sulphoacetate in rodents.

1. The disposition of (14C) coralyne sulphoacetate has been examined in the mouse and rat at three dose levels. 2. In both species the major route of excretion is biliary following either intraperitoneal or intravenous administration. In rats, 18-24% of the 14C is eliminated in the bile in the first 24 h and only 1-2% in the urine. Transport into bile appears to be active and the transport system saturable at the doses employed. 3. The majority of the biliary 14C in the rats is unchanged parent compound and a minority is associated with a metabolite. The maximum amount of metabolite is 12% at 10-30 min following the administered dose. 4. The initial plasma decay of (14C) coralyne following intravenous administration is rapid. Half-life values are 12-3, 16-2 and 2-41 min after doses of 13, 26 and 52 mg/kg respectively. 5. No sex differences were found in the rat in the parameters studied.

Animals↗
PubMed1976

Protein cross-linking properties of the antitumor agent inosine dialdehyde (NSC-118994).

Inosine dialdehyde (IdA), a new antitumor agent presently undergoing clinical evaluation in man, possesses two aldehyde groups that form stable complexes with a variety of biologic molecules containing amino groups. Complex formation of IdA with lysine, glycine, histidine, or bovine serum albumin (BSA) greatly reduces the cytotoxicity of IdA against L1210 leukemia in vitro. Complexes of IdA and BSA exhibit molecular weights ranging from 69,000 to greater than 800,000 as determined by Sephadex G-200 gel filtration, indicating that both aldehyde groups of IdA are functional and can cross-link protein molecules. The cross-linking of plasma proteins and the cross-linking of glycine to BSA were also observed. No interaction of IdA with nucleic acids, nucleic acid bases, or nucleosides was detected. The dialdehyde derivatives of other nucleosides also possessed cross-linking properties.

Aldehydes↗
PubMed1976

Pharmacology of antitumor agents from higher plants.

Some pharmacologic properties of nine antitumor agents from higher plants are described. The agents are vincristine, vinblastine the epiodophyllotoxin derivatives VM-26 and VP-16-213, maytansine, bruceantin, thalicarpine, camptothecin, and lapachol. When sufficient information is available, the agents are discussed with regard to their antitumor activity, mechanism of action, pharmacologic disposition, structure-activity relationships, and toxicity.

Animals↗
PubMed1976

Pilot studies with human interferon in Herpesvirus saimiri-induced lymphoma in owl monkeys.

The nature of Herpesvirus saimiri-induced disease in owl monkeys is described with emphasis on those biological parameters useful in monitoring the disease. These parameters are lymphocyte response to general mitogens, lymphocyte-infective centers, and antibody to virus-associated early antigen. Human interferon was used in treating owl monkeys with virus-induced leukemia. In 2 animals evidence was obtained that suggested a positive antileukemic effect.

Animals↗
PubMed1976

Pharmacologic disposition of inosine dialdehyde (NSC-118994) in mice, rats, dogs, and monkeys.

The pharmacologic disposition of inosine dialdehyde (IdA) was studied in mice, rats, dogs, and monkeys. 14C-IdA was utilized to follow plasma and tissue levels and patterns of excretion. Plasma radioactivity curves were multiphasic with an initial rapid component (half-life = 12-18 mins) followed by a much slower decline (half-life = approximately 3 days). As time progressed after the injection, an increasing fraction of the total plasma radioactivity was found to be associated with plasma proteins and was trichloracetic acid (TCA) insoluble. IdA interacts extensively with proteins and small molecules both in vivo and in vitro, forming complexes that do not dissociate under physiologic conditions. The pharmacologic disposition of IdA is dependent upon the relative extent of IdA interaction with protein macromolecules versus small transportable molecules. The major route of excretion was urinary with less than 50% of the dose excreted during the first 24 hours after iv administration in all species studied. IdA was recovered in the urine as complexes with urine constituents. There was no preferential uptake of IdA by any organ. All radioactivity remaining 24 hours after IdA administration was associated with plasma and cellular proteins and was nondiayzable and TCA insoluble. IdA was not a substrate for aldehyde oxidase and did not inhibit the activity of this enzyme.

Aldehydes↗
PubMed1975

Evaluation of the teratogenic activity of hycanthone in mice and rabbits.

Hycanthone has been tested for embryotoxic activity in mice and rabbits. Treatment of mice on days 6-11 of gestation produced little embryotoxicity at a dose of 12.5 mg/kg, but produced teratogenic effects at 25 mg/kg and induced almost complete intrauterine death at 50 mg/kg. Single injections on various days of gestation demonstrated that the mouse conceptus is most sensitive to hycanthone-induced teratogenesis on gestation days 6 and 7, at which time a high incidence of exencephaly and skeletal malformations was found. Hycanthone (50 mg/kg) given to pregnant mice on day 7 of gestation depressed DNA synthesis in embryonic tissue, an effect which was evident 30 minutes after drug treatment and which lasted at least 3 hours. Following a single injection of [3H-U]hycanthone into 7-day pregnant mice, radioactivity was rapidly cleared from the maternal plasma, having a half-life of 1-2 hours; higher levels of radioactivity were attained in the embryonic vesicles than in maternal plasma at all time intervals tested. Hycanthone also had embryotoxic activity in rabbits. A dose of 25 mg/kg increased the incidence of intrauterine death, and at 50 mg/kg both embryolethal and teratogenic effects were noted.

Abnormalities, Drug-Induced↗
PubMed1975

Nonhuman primate models for lymphoma, leukemia, and other neoplasms.

Herpesvirus saimiri (HVS) is an oncogenic virus for a variety of nonhuman primates. HVS does not produce overt disease upon inoculation in the natural host (squirrel monkey) but consistently induces neoplasms including lymphomas and lymphocytic leukemias in 4 other species of monkeys. Various drugs inhibit replication of HVS in vitro including cytosine arabinoside and adenine arabinoside. In addition, the lymphoma and leukemia induced in owl monkeys responds to vincristine and prednisolone, cyclophosphamide, cytosine arabinoside, and human interferon. Of the various chemical carcinogens studied, the antitumor agent procarbazine induces neoplasms in a variety of species including monkeys. Thus far this compound has induced acute myelogenous leukemia (AML), lymphoma, and hemangiosarcomas in macaques. We have induced primary liver tumors in macaques with several nitrosamines and aflatoxin B1 and these tumors produce alpha-fetoprotein (AFP) which can be assayed for both diagnosis and therapy. Thus far, therapy of hepatocellular carcinoma has been most successful with surgical resection; and the tumor mass and serum AFP have been less responsive to single agent chemotherapy. These nonhuman primate models are useful for an understanding of the cause, diagnosis, prevention, and treatment of the human disease.

Animals↗
PubMed1975

Diaphragmatic herniation of the liver in macaques demonstrated by intravenous hepatography.

A suspected diagnosis of diaphragmatic herniation of the liver in 2 monkeys (Macaca fascicularis and Macaca mulatta) was confirmed radiographically by using various contrast media. Experimental compound AG 60.99, which is selectively concentrated in the liver and spleen, allowed excellent visualization of these 2 organs and confirmed the presence of a portion of the liver in the right thorax. Cholografin Meglumine was subsequently utilized to determine the location of the gall bladder. Other potential uses for AG 60.99 were discussed.

Animals↗