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Biomedical subjects

R N Chute

Publications and source records attributed to R N Chute.

At least 19 recordsLinked to original sources

Metabolism and storage of catecholamines in rats with pheochromocytoma implants.

New England Deaconess Hospital rats implanted with a pheochromocytoma P259 became hypertensive and showed high concentrations of plasma dopamine (42.0 +/- 14.6 ng/ml) and norepinephrine (45.7 +/- 8.4 ng/ml). However, the norepinephrine content of several peripheral tissues of these rats did not differ from those of the New England Deaconess Hospital control rats, and their dopamine content, although slightly higher, was much lower than would have been expected from the plasma dopamine levels. Methylation by catechol-O-methyltransferase did not appear to play a major role in the inactivation of tissue catecholamines since there were no noticeable increases of normetanephrine or 3-methoxytyramine in the tissues of the rats with pheochromocytoma. There was also no increase in conjugated dopamine, in either the sulfate or glucuronide form, in the plasma or tissue of the hypertensive rats, although injection of L-dopa induced a large increase in dopamine sulfate in the plasma and urine of these rats. This finding indicated that, although their sulfoconjugation mechanism was intact and not affected by the pheochromocytoma, it did not participate in the metabolism of dopamine released by the tumor into the blood. On the other hand, plasma and urine of tumor-bearing rats exhibited abnormally high concentrations of homovanillic acid, the main metabolite of dopamine resulting from monoamine oxidase action. In contrast to the control rats, intravenous infusion of free dopamine in rats with pheochromocytoma had no effect on plasma free dopamine levels but increased homovanillic acid levels considerably. The present data underline the important role of monoamine oxidase in the removal of excessive quantities of catecholamines released by the tumor in New England Deaconess Hospital rats with the pheochromocytoma implant.

Adrenal Gland Neoplasms↗

Mesothelioma relative to asbestos, radiation, and methylcholanthrene.

The carcinogenicity of chrysotile asbestos fibers (Canadian and Rhodesian) for the mesothelium of pleura and peritoneum of NEDH rats was explored by injection of 2 mg of asbestos fibers suspended in saline intratracheally, intrapleurally, or intraperitoneally, with or without ancillary radiation treatment (1,000 rad to the whole body of parabiont rats or 2,000 rad to the right thorax of single rats), or alternatively, by injection of asbestos plus 1 mg of 3-methylcholanthrene. A highly significant incidence of mesothelioma (3.8%) was noted in 159 rats treated with asbestos alone, as compared with 0.1% in 1,417 control rats. Additional treatment with radiation or 3-methylcholanthrene increased this incidence to 11.8% and 25.5%, respectively, the latter increase alone being significant at the .01 level of probability.

Animals↗

Serially transplantable chemically induced rat islet cell tumor.

A serially transplantable, chemically induced pancreatic islet cell tumor was developed in Lewis rats. The original tumor was induced by the administration of streptozotocin and nicotinamide. It was subsequently maintained by ip or sc transplantation of tissue fragments into recipient animals. Tumors generally grew to 0.5--2.0 cm in diameter within 3--4 months of transplantation. They were well encapsulated, without gross evidence of metastasis. Peroxidase immunocytochemical staining revealed a predominance of insulin-positive cells. Somatostatin-positive cells were also present and varied widely in numbers between different tumors. In addition, small numbers of glucagon-positive cells were observed in all of the tumors. On electron microscopy, cells containing secretory granules, indistinguishable from nonneoplastic beta-cells, were most abundant. Other granulated cells were also observed, but the granule morphology was not identical to that of any of the other classically described islet cell types. Tumor extracts contained an average of 3260 micrograms insulin, 22.6 micrograms somatostatin, and 0.84 micrograms glucagon per g wet wt of tissue. Tumors caused marked, progressive hypoglycemia in recipients, with plasma glucose levels frequently falling below 30 mg/dl before death. Furthermore, the recipients' islets were markedly reduced in size due to a decreased beta-cell volume.

Adenoma, Islet Cell↗

Hormonally induced tumors of the reproductive system of parabiosed male rats.

Parabiosis of intact male rats to castrated males or oophorectomized females for a period of approximately 20 months resulted in three interstitial cell tumors of the testis. When unilateral nephrectomy was added to the parabiotic procedure in ten pairs, eight interstitial cell tumors of the testis and four adenocarcinomas of the prostate occurred in the target male parabionts. These changes were preceded by elevations in luteinizing and follicle-stimulating hormone levels in the serum of the castrates and high levels of testosterone and, to a lesser degree, of androstenedion in the target partners developing the tumors.

Adenocarcinoma↗

Late effects of successive massive doses of radiation on parabiont rat pairs.

Parabiosis of rats permits one partner to survive 1000 R X-radiation if the other is shielded. This dose to the previously shielded partner after intervals of 5, 10 or 30 days tests the ability of the first irradiated partner to recover and, in turn, support the second. The effectiveness of this can be measured by the late effects induced in the pair. Lifespan was shortened by 100--150 days following a 5-day interval, by 30 days following a 10-day interval and not shortened following a 30-day interval. The incidence of leukaemia was about 6 per cent in each group, close to that in control pairs. Shortening the interval between the irradiations decreased the average age of death from leukaemia. No solid lymphoid tumours were induced in the doubly irradiated pairs. The incidence of osteogenic sarcoma was 1.6 per cent in controls and 12.9 per cent in the pairs with both partners irradiated.

Animals↗

A transplantable insulinoma in the rat.

A transplantable insulinoma was developed in inbred albino rats of the NEDH strain. The original tumor, 1 cm in diameter, was removed from the pancreas of a male parabiont 566 days folowing 1000 rads (10J/kg) of total body x-irradiation. The time required for implanted fragments to grow to 0.5-1.5 cm in diameter decreased from 5-8 months in the first generation to 2-5 months in the seventh generation. Successful transplantation in male animals followed for 4 or more months after transplantation was significantly greater than in female animals followed for a similar period of time (96% versus 69%). Light and electron microscopy revealed that the tumors consisted predominantly of well-granulated beta cells. Ultrastructural studies also showed small numbers of D-cells. Tumor extracts contained an average of 223 units of immunoreactive insulin and 25.9 mug of immunoreactive somato-statin per gram wet weight of tissue. Tumors generally produced increasingly profound hypoglycemia within 2-4 months following transplantation, with plasma glucose levels frequently falling to 40 mg/100 ml or lower prior to death. Removal of tumors from chronically hypoglycemic animals resulted in transient rebound hyperglycemia with plasma glucose levels above 300mg/100 ml within the first 24 hr and a gradual decline to normal levels of 129 mg/100ml in 2-4 days. These observations correlated with findings of marked atropy and degranulation of the beta cells in the pancreata of tumor-bearing animals, and with gradual return of normal light microscopic morphology following tumor removal.

Adenoma, Islet Cell↗

The effect of parabiosis on life-span of rats stressed by radiation.

The life-spans of four series of NEDH rats were compared: (1) single control rats, (2) single rats irradiated with 1000 R, (3) control parabiont rats, (4) parabiont rats one of which had received 1000 R. The stress of radiation (1000 R) produced a median life shortening of 571 days in single rats. Parabiosis followed by irradiation (1000 R) of a member of the pair shortened life 132 days. Parabiosis alone produced a median life shortening of 62 days. Ninety percent of the older irradiated parabiont pairs died with one or more tumors present. Parabiosis largely protected animals from the gastrointestinal radiation syndrome.

Animals↗

The effect of nephrectomy on the incidence of breast carcinoma in irradiated parabiosed rats.

The incidence of carsinoma the breast in parabiosed female NEDH rats is 2.5%. When one member of such a pair is irradiated, the incidence rises to 11% in the irradiated partner and 10% in the nonirradiated partner. If in such a pair of rats one kidney is removed from each partner, the incidence of breast carcinoma rises fivefold in the nonirradiated partner. The factors involved in such an increase probably have to do with alteration in retention, interchange, and feedback of the pituitary and ovarian hormones.

Adenocarcinoma↗

Pheochromocytoma.

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Adrenal Gland Neoplasms↗

Gamma-ray induction of malignant tumors in rats.

Sources of protracted gamma radiation adjacent to bone were found to induceosteogenic sarcoma in half of the exposed males. Osteogenic sarcomas appeared in 3 males remote from the radioactive sources and may not have been radiation induced. Some tumors were small enough so that the site of origin could be determined accurately: some arose from endosteum, others from periosteum. Although portions of the skeleton in the female rats incidentally received doses of over 20,000 rads, no osteogenic sarcomas developed in them. Parauterine sources induced adenocarcinoma of the endometrium in 14 of 32 rats (44%). The incidence of carcinoma of the ovary (12%) was lower than expected. Carcinomas of the breast were frequent, but often distant from the source. Increased total dose, which was usually related to length of time of exposure, produced an increased incidence of cancer and a shortening of the latent period. However, extremely high doses (over a million rads to bone and hundreds of thousands to the uterus) at times failed to induce cancers.

Adenocarcinoma↗