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C M Ambrus

Publications and source records attributed to C M Ambrus.

At least 37 records · Page 2Linked to original sources

Effect of second tumors and of prostaglandin-leukotriene inhibitors on radiation therapy of transplanted rodent tumors.

The prostaglandin and leukotriene inhibitor sodium meclofenamate (SM) failed to influence radiation therapy induced regression of 6C3HED Gardner lymphosarcoma in C3H mice. Recurrence after radiation therapy, however, was reduced by treatment with SM. During these experiments, we observed that if a tumor was "cured" by radiation therapy, it required inoculation of a larger number of cells to establish a second tumor. Presumably, a certain degree of immunity has developed. On the other hand, if a second tumor was already established, less tumor cells were needed to establish a third tumor. This may be related to immuno-suppressor products of the second tumor. This effect could be partly inhibited by SM, suggesting that prostaglandins and leukotrienes may be involved in this phenomenon.

Animals↗

Antineoplastic effect of the xanthine derivative Trental.

The xanthine derivative, Trental (pentoxifylline) was found to inhibit several human leukemic and lymphoma cell lines in tissue cultures. Optimal concentrations were less inhibitory for a normal B-lymphocyte cell line then for the neoplastic cell lines. In fact, small concentrations stimulated DNA synthesis in the normal cell line. Trental and beta-interferon appeared to be additive synergists at certain dosages. Possible mechanisms are discussed.

B-Lymphocytes↗

Studies on the pathophysiology and therapy of osteoporosis.

Etiologic and pathologic factors in clinical osteoporosis are reviewed. Techniques were developed to determine total skeletal calcium content with in vivo neutron activation analysis and to induce osteoporosis (in about three months) with low calcium diet, corticosteroid or heparin treatment in experimental animals. Genetic influence was demonstrated: C3H/St (Ha) mice were more susceptible to osteoporosis by all three modalities than C57B1/6 (J) mice. Fluoride was ineffective in preventing osteoporosis induced by either of these three modalities. Heparin induced osteoporosis was prevented by conjugated estrogens, progestins or their combinations. Progestins were shown in other studies to inhibit estrogen induced metaplasia and neoplasia. Combining estrogens with progestin may result in an increased therapeutic index for the prevention of postmenopausal osteoporosis. Human and salmon calcitonin, Deca - Durabolin, an anabolic steroid, Mopidamole, a pyrimidopyrimidine derivative, Trental, a methylxanthine derivative, certain 2-thiophene carboxylic acid derivatives and imidazoquinazolines exhibited anti-osteoporotic effects.

Animals↗

Experience with hypercalcemia and osteoporosis of neoplastic disease.

Hypercalcemia and hypercalcemic crisis are common and often life threatening complications of neoplastic disease. Even moderately increased mobilization of skeletal calcium can result in significant osteoporosis. This in turn can give rise to pathologic fractures, often followed by pulmonary fat embolism and death. Bone pain is at times the first sign of neoplastic disease and the reason for seeking medical help.

Adrenal Cortex Hormones↗

Legionella and the enterobacterial common antigen.

Legionella pneumophilia Philadelphia 1 and Knoxville 1 were examined by in vitro hemagglutination and dermal hypersensitivity reactions in guinea pigs for the presence of the enterobacterial common antigen. No ECA was found and no cross reactivity was demonstrated between ECA and the proteinaceous cross reacting antigen.

Animals↗

Determination of aromatic amino acids by ion-pair reversed-phase liquid chromatography in human sera from healthy and phenylketonuric individuals.

A simple chromatographic procedure is described for simultaneous analysis of aromatic amino acids in serum samples obtained from normal individuals and from phenylketonuric patients. Quantitative measurement of phenylalanine, tyrosine, histidine and tryptophan is made in samples as small as 10 microliter after deproteinization with trichloroacetic acid. With phenoxyacetic acid as the internal standard, samples are analyzed by reversed-phase chromatography isocratically by an ion-pairing agent in the eluent, and the amino acids are detected with the UV detector at 210nm. Total analysis time was about 30 minutes. Using this method in serum samples from phenylketonuric patients phenylalanine was increased (as expected), and histidine was decreased, at a statistically significant level.

Amino Acids↗

Prostaglandin E2 production by human tumors. Defense mechanism against the host? A preliminary report.

Immunoreactive PGE2 was determined in 11 surgically removed malignant tumors. When compared to adjacent non-malignant tissues PGE2 content was significantly higher in the neoplastic tissues. These findings support the view that PG may play a role in cell proliferation and/or vascular supply to tumor tissues. The hypothesis was also discussed that PGE2 may represent a tumor against host defense since it can decrease spontaneous and antibody dependent cytotoxicity. PGE2 may also play a role in tumor induced osteoporosis and hypercalcemia. If this hypothesis is correct PGE2 synthesis inhibitors may be employed as auxiliary antitumor agents.

Dinoprostone↗

Effect of sodium meclofenamate on radiation-induced esophagitis and cystitis.

Stumptailed monkeys (Macaca arctoides) received 2000 rad irradiation to the upper half of the esophagus and to the bladder by a 6-MEV linear accelerator. Endoscopy and biopsy was obtained from these organs weekly for 3 weeks. At the end of this period, the animals were autopsied and histopathologic examination undertaken. Sodium meclofenamate in doses of 5-20 mg/kg/day p.os was found effective in reducing or preventing radiation induced esophagitis and cystitis.

Animals↗

Studies on osteoporosis X. Effect of estrogen-progestin combination on heparin-induced osteoporosis.

Neutron activation analysis was employed to determine total body calcium in C3H/St(Ha) female mice. As 99% of body calcium is in bone, loss of calcium was used as an index of bone loss (osteoporosis). Heparin (500 U/kg b.i.d. caused bone loss in 3 months. Premarin (2 mg/kg q.d.) or norethindrone (40 mg/kg q.d.) alone prevented this osteoporosis. A Premarin-norethindrone combination (2 mg - 10 mg q.d. respectively) appeared to be somewhat more effective than either agent alone, but this difference was not significant at the 5% level. Combinations of estrogen and progestins may prevent metabolic bone disease at the same time reducing the danger of estrogen induced neoplasia.

Animals↗

In vivo safety of hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase in a large animal model for phenylketonuria.

Hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase (PAL) were developed for the in vivo depletion of phenylalanine (Phe) in circulating blood. A series of experiments was conducted with a large animal model in order to explore its safety for clinical use. The level of red blood cells, white blood cells and platelets did not change during a 2-hr application of the reactors in anesthetized, heparinized dogs and monkeys with experimental hyperphenylalaninemia. No increase in blood urea nitrogen was observed due to generation of ammonia from PAL-catalyzed Phe breakdown. The other metabolic product, trans-cinnamic acid, was reported to be nontoxic. Repeated application of the PAL-reactors to the same animals did not produce untoward physiological or immunological reactions. These data suggest that PAL-reactors may be safe for in vivo use to control excess Phe brought about by fever, infection or pregnancy in phenylketonuric individuals otherwise balanced by a Phe-poor diet. Application of PAL-reactors may serve as a model for extracorporeal enzyme replacement in enzyme-deficiency diseases.

Ammonia-Lyases↗

Protection of normal tissues with 2-aminoethylisothiouronium during local pelvic radiation in monkeys.

Intestinal and bladder injury are the main limiting factors to radiation therapy in patients with pelvic neoplasms. 2-Amino-ethylisothiouronium (AET) is a radiation-protective agent when given systemically but absorbs poorly from the intestines. Accordingly, it was explored for the local protection of the bowel and bladder during radiation to the pelvis. Radiation localized to the pelvis in various high fractionated doses and various schedules was applied to pairs of stumptailed monkeys (Macaca arctoides): one was always a control; and the other was treated with AET. AET was applied to the bladder through a catheter and to the rectum with a cotton tampon during the time of radiation. After radiation, AET was removed by repeated washings. Control animals developed hemorrhage, diarrhea, and emaciation and died at various times after completion of the radiation course; biopsy of rectal mucosa showed severe radiation damage. AET-treated animals had only occult blood in the stools and suffered slight weight loss; rectal biopsies showed normal tissues 2 weeks after radiation.

Animals↗

Studies on platelet aggregation inhibitors in vivo. X. Relationship to thrombolysis.

Human labeled fibrin clots were inserted into femoral veins of stumptailed monkeys (Macaca arctoides). Thrombolysis was slightly increased by treatment with the platelet aggregation inhibitor pentoxifylline. This agent significantly potentiated the thrombolytic effect of urokinase activated human plasminogen. Pentoxifylline was also found to release plasminogen activator activity into the circulation.

Animals↗

Study of platelet aggregation in vivo. IX. Effect of nafazatrom on in vivo platelet aggregation and spontaneous tumor metastasis.

Nafazatrom (Bay g 6575) was explored for its ability to inhibit platelet aggregation. In vitro, it had no effect on ADP, serotonin, epinephrine, or collagen induced platelet aggregation in platelet rich plasma of monkeys. On the other hand, in vivo it was a powerful inhibitor of ADP induced platelet aggregation as measured by the in vivo platelet aggregation recording instrument described previously (Ambrus et al., 1976). This effect was potentiated by dipyridamole. On the other hand, following parenteral administration of Bay g 6575, no ex vivo inhibition was noticed of ADP, serotonin, epinephrine, and collagen induced platelet aggregation. The hypothesis was presented that Bay g 6575 acts by increasing prostacyclin synthesis and/or release or interferes with its decomposition. This may explain in vivo activity; rapid decomposition may explain inability to demonstrate ex vivo activity. This also explains potentiation by the phosphodiesterase inhibitor dipyridamole. Bay g 6575 also was highly effective as a platelet aggregation inhibitor in monkeys after oral administration. In mice, Bay g 6575 increased circulation time of intravenously injected polyploid Ehrlich ascites tumor cells. In Furth-Wistar rats implanted with Furth-Columbia Wilms' tumor, in A/J mice implanted with C1300 neuroblastoma and in Wistar rats implanted with SMT-2A (Kim) breast cancer, Bay g 6575 significantly reduced spontaneous pulmonary metastasis. On the other hand, no effect was seen in the metastatic rate of NIH renal adenocarcinoma in BALB/cCr mice.

Adenocarcinoma↗

Platelet cancer cell interaction in metastasis formation. Platelet aggregation inhibitors: a possible approach to metastasis prevention.

Abnormal platelet aggregation on circulating and lodged cancer cells may play an important role in the early stages of metastasis formation. The immediate drop in the number of circulating platelets following intravenous injection of Walker-256 carcinosarcoma cells in rats represents the experimental counterpart of the morphologic finding of tumor cells associated with tumor clusters in the pulmonary arterioles and capillaries.

Animals↗