PubMed Health⌕ Search

Biomedical subjects

R L Noble

Publications and source records attributed to R L Noble.

At least 55 records · Page 3Linked to original sources
PubMed1980

Production of Nb rat carcinoma of the dorsal prostate and response of estrogen-dependent transplants to sex hormones and tamoxifen.

Carcinoma in the dorsal prostate of Nb rats was produced by prolonged treatment with androgen or androgen plus estrogen. The most effective combination was androgen followed by estrogen, resulting in an incidence of 50% in 10 rats. In such a case, the rats did not show evidence of androgenization. Transplants were usually not sensitive to hormones, but an estrogen-dependent tumor (Nb-2Pr-E) was successfully transplanted in estrogenized hosts. Cells of estrogen-dependent tumors did not grow in males but remained dormant and could be stimulated to grow after many months by estrogen treatment. The resulting tumors remained estrogen dependent, with one exception which was autonomous. Tumors regressed following estrogen removal but eventually showed a spontaneous regrowth which was then found to be autonomous. In the case of growing tumors, the reduction of estrogen to subthreshold doses for maximal growth allowed stationary or only slow growth of the tumors, but these remained estrogen dependent. Estrogen-dependent tumors responded to tamoxifen treatment by a cessation of tumor growth or regression despite continued estrogen treatment. Tumor regrowth eventually took place after prolonged tamoxifen treatment, but the tumors remained estrogen dependent when transplanted.

Adenocarcinoma↗
PubMed1980

Development of androgen-stimulated transplants of Nb rat carcinoma of the dorsal prostate and their response to sex hormones and tamoxifen.

Androgen-stimulated tumors of the dorsal prostate were derived from an estrogen-dependent tumor of Nb rats (Nb-2Pr-E). The change followed repeated androgen treatments in a rat bearing a tumor which had regressed after estrogen removal. The eventual tumor regrowth provided tumor transplant lines, Nb-2Pr-A, which grew in normal or androgenized males, slowly in castrates, but not in estrogenized females. The Nb-2Pr-A growing tumors regressed after treatment with estrogen, and tumors which eventually regrew were autonomous. Slow tumor growth in castrated animals also responded to estrogen treatment. Tamoxifen, an antiestrogen, caused tumors growing in males to become stationary or regress. Regrowth of tumors after they had responded to tamoxifen again responded to castration or estrogen. Tumors which escaped from estrogen treatment or were autonomous did not respond to tamoxifen. The most effective sequence for treatment was tamoxifen followed by castration and, finally, estrogen. Tamoxifen treatment or castration allowed tumors to remain hormone responsive, whereas initial estrogen treatment prevented response to subsequent therapy and led to an autonomous change.

Androgens↗
PubMed1979

Comparison of Bungarus caeruleus venom with the venom from which a putative cholinergic ionophore marker was isolated.

Comparisons are described between Bungarus caeruleus venom and the actual venom from which a putative marker for the cholinergic ionophore, called ceruleotoxin, was isolated. The venoms are shown to be different by two procedures for ion exchange chromatography and by isoelectric focusing on polyacrylamide gel. The activities of the purified "ceruleotoxin" as an inhibitor of acetylcholine receptor-mediated ion flux and as a phospholipase have been reported (Bon & Changeux, 1977b). The results reported herein suggest that this toxin is from an unknown origin.

Bungarotoxins↗
PubMed1977

Sex steroids as a cause of adenocarcinoma of the dorsal prostate in Nb rats, and their influence on the growth of transplants.

The development of adenocarcinoma of the dorsal prostate of Nb rats following prolonged treatment with pellets of testosterone propionate alone or with esterone allowed the establishment of transplantable tumor models. Whereas most transplants were autonomous and not influenced by hormones, one estrogen dependent tumor was studied in detail. This tumor would only grow in estrogenised hosts, cells remaining dormant in normal animals. Removal of estrogen from animals with growing tumors led to tumor regression but with progression and eventual regrowth of tumors which were autonomous. Replacement with lower doses of estrogen reduced the extent of regression and prevented autonomous change. When a regressed estrogen dependent tumor was exposed to prolonged treatment with testosterone propionate pellets, the eventual regrowth was found to be androgen dependent and would not grow in estrogenised animals. Progression could apparently be directed by this procedure from estrogen to androgen dependency.

Adenocarcinoma↗
PubMed1977

Human somatotropin 53. Synthesis and biological activity of the amino terminal fifty-four residue fragment.

The amino terminal 54 residue peptide fragment of human somatotropin [Cys(Gam)53]-HGH-(1-54), has been synthesized by the solid-phase method. The symmetrical anhydride and active ester coupling methods were used exclusively. The synthetic product was purified by gel fitration isoelectric focusing, and partition chromatography. It was found to be homogeneous by six additional criteria. In complement fixation experiments the synthetic product was immunologically active with antisera to HGH and [cys(Cam)53]-HGH-(134). Antiserum raised against the synthetic product was immunologically active in the homologous assay and with HGH,[Cys(Cam)53]-HGH-(1-134), and [Cys(Cam)53]-HGH-(15-125). The synthetic fragment exhibited 53% of the activity of [Cys(Cam)53]-HGH-(1-134) in the rat tibia assay.

Amino Acid Sequence↗
PubMed1977

Hormonal control of growth and progression in tumors of Nb rats and a theory of action.

A continuation of previous studies of hormone-dependent tumors in various organs in Nb rats concerns the effects of removal of the hormone stimulus from animals with growing tumors. Tumor regression usually followed this procedure, and in various models it was associated with an increased survival of the animal. A regressed tumor could be caused to grow at any time by estrogen treatment, and the resulting tumor remained hormone dependent, although some progression might occur. Continuous breeding rarely affected the growth or progression of transplanted adrenal or breast carcinomas. When spontaneous regrowth of tumors took place following removal of the estrogen stimulus all types of tumors (except leiomyomas of the uterus, showed progression usually to autonomy, and in the case of male rats bearing breast carcinomas it was inevitable. The substitution of pellets containing a reduced level of estrone to determine which prevented regression and allowed uninterrupted growth offered an assessment of the type or amount of hormone required for the growth of different tumors. By means of such a model of breast cancer in male rats, it was possible to demonstrate that a reduction in hormone levels sufficient to prevent advancing tumor growth, but adequate to reduce the extent of regression, also reduced the frequency or prevented the development of autonomous change. Although regression per se was not a prerequisite for autonomous change, the paradox was evident that progression towards autonomous growth was accelerated with procedures expected to check tumor growth and was minimal with procedures that accelerated it. Liver metastases of hormone-dependent adrenal carcinomas continued growth and could not be influenced by removal of estrogen, although the primary transplant regressed. When such metastases were transplanted, they were not found to have progressed to autonomy but retained a hormone-dependent status. Some tumors, when maintained in estrogen-conditioned hosts, apparently showed a reversion to a more hormone-dependent cell type rather than the expected progression towards autonomy. A theory is suggested to explain the experiments findings on the development and control of estrogen-responsive tumors.

Adrenal Gland Neoplasms↗
PubMed1977

The distribution of [3H]vinblastine in tumor and host tissues of Nb rats bearting a transplantable lymphoma which is highly sensitive to the alkaloid.

A new transplantable lymphoma in Nb rats responded dramatically to treatment with vinblastine (VLB). A single i.p. injection of VLB, 0.8 mg/kg, caused even highly advanced tumors to regress until they were no longer palpable. or investigation of the hypothesis that the oncolytic response may reflect a special affinity of VLB for the tumor, lymphoma-bearing rats were given an i.p. injection of -e13H]VLB, and the levels of radioactivity and [3H]VLB in the tumor and host tissues were determined as a function of time. Radioactivity was concentrated by the lymphoma relative to the blood (mostly as unchanged [3H]VLB) at levels that showed only a modest decline over a period of at least 48 hr. During this time the [2H]VLB in both the plasma and whit blood cell fraction of the blood declined markedly and continuously to very low levels. Thymus and lymph nodes resembled the lymphoma in showing a long-term retention of radioactivity. The levels of radioactivity in the spleen, liver, and bone marrow were initially much higher than that in the tumor but decreased markedly with time. In addition very little of the radioactivity remaining in the spleen and liver at 48 hr was due to [3H]VLB, and by this time the VLB concentration in these tissues was much lower than in the tumor. It is suggested that the chemotherapeutic response of the lymphoma may be related to the continuing presence of a significant concentration of VLB in this tumor after the plasma VLB had fallen to very low (subantimitotic) levels.

Animals↗
PubMed1977

The development of prostatic adenocarcinoma in Nb rats following prolonged sex hormone administration.

The low spontaneous incidence of grossly recognizable adenocarcinomas of the dorsal lobe of the prostate in Nb rats over 13 months old (0.45%) was increased to 18.38% in 130 rats by prolonged treatment with pellets of suitable sex hormones. Although testosterone propionate alone was effective, if the testosterone propionate was combined with treatment by estrone carcinomas of the prostate occurred after a shorter interval. Tumors tended to metastasize and transplanted readily, and all were autonomous, with a single exception that exhibited the growth pattern of a typical estrogen-dependent tumor.

Adenocarcinoma↗
PubMed1975

Spontaneous and estrogen-produced tumors in Nb rats and their behavior after transplantation.

Tumors in rats of the Nb strain, arising either spontaneously or after prolonged treatment with s.c. pellets of estrogen, were transplanted to establish whether hormone conditioning was required for their growth. Whereas all spontaneous tumors arising in males and many of those in females were autonomous on transplant, most of those arising in estrogenized rats continued to require hormones for growth after transplantation. The latter included carcinomas of the adrenal cortex, breast, pituitary ectopic tissue, ovary (thecomas), Leydig cells of testis, thymus, pancreas,salivary glands, oribital gland (fibroadenoma), liposarcoma, and lymphoma. Many of the tissues of origin of the tumors have not been considered to be under theinfluence of estrogens. A type of hormone-responsive tumor that was inhibited by estrogen and that grew only in normal rats is described. Ali estrogens tested, including estriol , were interchangeable in action. The incidence of the more common tumors of the adrenal, breast, and pituitary was very low in normal rats, but higher in females. All tumors were more common after estrogenization in both sexes, particularyly in older animals. The secretion of steroids and pitiutary hormones by many tumors led to obvious biological effects. Pituitary secretion led to severe lesions frequently associated with diseases in humans, but the signs of such diseases in the rat apparently were hormone dependent and disappeared if the tumor was removed. The overall results raised the possiblity that estrogens were not carcinogenic per se but stimulated the growth of previously altered cells and that, following their transplantation, this hormone requirement was retained. Irrespective of the mechanism of carcinogenesis, hormone-dependent tumor growth was not irreversible but was controlled in an unexpectedly wide spectrum of organs by exogenous estrogen. Host factors may play a major role in controlling the growth of many tumors and the ultimate course of the disease.

Adrenal Cortex Neoplasms↗
PubMed1975

A classification of transplantable tumors in Nb rats controlled by estrogen from dormancy to autonomy.

Transplantable tumor lines were previously established from a variety of estrogen-induced tumors in Nb rats, including tumors of the adrenal cervix, salivary gland, and pancreas, a lymphoma, and a liposarcoma. Spontaneous tumors, however, were found to arise in untreated females and showed the same characteristics. Tumor growth was dependent upon or influenced by estrogen when assessed in estrogenized and unconditioned hosts. Intermitten estrogenization was effective, but tumor growth took place more slowly. The type of response observed led to a new classification of five types of hormone-responsive tumors including tumors inhibited by estrogen. Estrogen-dependent tumor cells might remain dormant indefinitely and not grow in unconditioned animals until stimulated to grow by estrogen. The growth rate of hormone-dependent adrenal carcinomas was related to the amount of estrogen. Tumor growth started more rapidly in the presence of low estrogen dose levels in old rats used as hosts than it did in young rats. Breast carcinomas required the largest amount of estrogen for growth, whereas ovarian thecomas would grow in normal females but not in males. The growth rate in conditioned hosts of most transplanted tumors (some have maintained hormone dependency over 10 years) increased over successive generations. Progression, however, towards a more autonomous state after repeated transplantations was remarkably slow, and a sudden change to autonomy was rarely noted. In contrast, transplants of 9,12-dimethylbenz(a)anthracene-induced mammary carcinomas progressed rapidly to autonomy. Fould's concept of progression (2, 3) has been discussed but the described classification of tumors under hormone influence apparently allows a more detailed analysis of definition of different types of progression.

Adrenal Gland Neoplasms↗
PubMed1973

The Leeds regional quality control scheme for clinical biochemistry: a progress report.

The results from a regional quality control scheme for clinical biochemistry are analysed. Comparison with results from an earlier period shows that the quality of several of the 15 routine analyses has improved. The methods by which the sera are produced and distributed, and the weekly results are analysed, are described. Each of the 25 laboratories receives an individual weekly computer printout within 24 hours of the deadline for the receipt of results. At the end of each six-month period a printout is produced ranking each laboratory for ;accuracy' and ;precision' for each test.

Alkaline Phosphatase↗