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Biomedical subjects

M M Webber

Publications and source records attributed to M M Webber.

At least 55 records · Page 3Linked to original sources

Selenium prevents the growth stimulatory effects of cadmium on human prostatic epithelium.

Cadmium has been implicated in the increase in prostate cancer incidence in men exposed to high levels. A decrease in zinc and a concomitant increase in cadmium levels in the human prostate has been shown. The role and mechanism of cadmium action in prostate carcinogenesis is not clear. Selenium, on the other hand, has been shown to inhibit carcinogenesis in several animal systems. Results show that cadmium stimulates the growth of human prostatic epithelium in vitro, between 10(-9) M and 10(-7) M concentrations. Selenium, at concentrations between 10(-12) M and 10(-7) M shows no growth stimulatory or inhibitory effects on these cells. However, when present at 10(-8) M level, selenium inhibits the growth stimulation induced by cadmium. These results suggest that selenium may be useful in counteracting the effects of cadmium in the human prostate and offer possibilities for investigations on the protective effects of selenium in cadmium-related carcinogenesis in man.

Aged↗

Dexamethasone and retinyl acetate similarly inhibit and stimulate EGF- or insulin-induced proliferation of prostatic epithelium.

Prostatic epithelium proliferates in a defined medium consisting of basal medium RPMI1640 containing transferring (1 microgram/ml), EGF (10 ng/ml), and insulin (3.7 micrograms/ml or 0.1 IU/ml). Although neither dexamethasone nor retinyl acetate affected the proliferation of prostatic epithelium in RPMI1640 containing transferrin alone, they modify the mitogenic effect of EGF and insulin. Dexamethasone at 10(-10) M or retinyl acetate at about 3 X 10(-9) M inhibits proliferation stimulated by EGF. Higher concentrations of dexamethasone (10(-8) - 10(-6) M) or retinyl acetate (3 X 10(-8) - 10(-7) M) enhance the mitogenic activity of EGF. Dexamethasone had a similar effect in the presence of insulin. However, retinyl acetate stimulated, but did not significantly inhibit, proliferation in the presence of insulin. These results suggest that both dexamethasone and retinyl acetate, and possibly other glucocorticoids and retinoids, may regulate the proliferation of prostate epithelium by a dose-dependent modification of the activity of insulin and EGF.

Aged↗

Zinc levels in zinc-stabilized insulin are inhibitory to the growth of cells in vitro.

Adult human prostatic epithelium was cultured in a defined medium consisting of RPMI 1640 supplemented with transferrin, insulin, epidermal growth factor, dexamethasone, and vitamin A. In the presence of insulin, stabilized with zinc, maximum epithelial multiplication was obtained at an insulin concentration of 0.03 to 0.1 U/ml, corresponding to a zinc concentration of 1.4 X 10(-7) M. At higher insulin concentrations, growth stimulation declined. Zinc-free insulin, on the other hand, stimulated cell multiplication with an optimum concentration of 0.3 to 1.0 U/ml. At this concentration, the maximum growth was twice that obtained with zinc-stabilized insulin. Results demonstrate that growth inhibition caused by zinc limits the concentration of zinc-stabilized insulin, which can be used in serum-free, defined culture media.

Aged↗

Contrast venography vs. radionuclide venography: a study of discrepancies and their possible significance.

In 51 instances, patients underwent radionuclide venography with technetium 99m-labeled macroaggregated albumin followed by contrast venography. The criteria used for diagnosis of a positive radionuclide venogram (flow pattern and retention of radionuclide) were evaluated. Cases in which there were discrepancies between the two studies were analyzed. Multiple factors were found to result in a lack of correlation between the two studies. These are: failure to recognize nonfilling of the deep venous system on the radionuclide venogram, disparate distribution of the venographic imaging agents, presence of varicose veins, large venous valves, previous femoral venipuncture, postsurgical narrowing with obstruction, age of the thrombus, and other factors. These factors and their implications with respect to venographic technique are discussed.

Animals↗

Identification of hip surface arthroplasty failures with TcSC/TcmDP radionuclide imaging.

The roentgenographic identification of femoral component loosening after hip surface arthroplasty is often impossible because the metallic femoral component obscures the bone-cement interface. The use of combined technetium sulfur colloid and technetium methylene diphosphonate radionuclide imaging has been especially useful in the diagnosis of loosening. In 40 patients, follow-up combined TcSC and TcmDP scans at an average of three, nine, and 27 months postoperation revealed significant differences in the isotope uptakes in patients who had loose prostheses compared with those without complications. Scans were evaluated by first dividing them into eight anatomical regions and then rating the uptake in each region or 'zone' on a five-point scale. Results were compared using the Student's t-test and differences were noted between normal controls and patients who had femoral component loosening. Combining both TcSC and TcmDP studies increased the statistical significance obtained when comparing patients who had complications to those in the control group.

Aged↗

Polypeptide hormones and the prostate.

Results presented in this paper demonstrate that both insulin and prolactin have direct effects on the growth and functions of prostatic epithelium. They also act on the prostate indirectly by potentiating the effects of testosterone on these cells. Both are capable of inducing cell multiplication and increasing the activity of ornithine decarboxylase in cells. However, the intracellular events which follow the interaction of these hormones with the cell membrane receptors are not clearly understood. Little is known at the present time about the specific effects of insulin and prolactin on prostatic growth regulation and function and about their interactions with other protein and steroid hormones. A considerable amount of further research is needed to establish the basic influences of insulin and prolactin on the prostate. This inquiry is essential before the role of these hormones in normal and abnormal growth of the prostate can be understood.

Aging↗

Radionuclide bone imaging.

Radionuclide bone imaging of the skeleton, now well established as the most important diagnostic procedure in detecting bone metastases, is also a reliable method for the evaluation of the progression or regression of metastatic bone disease. The article concentrates on the technetium-99m agents and the value of these agents in the widespread application of low-dose radioisotope scanning in such bone diseases as metastasis, osteomyelitis, trauma, osteonecrosis, and other abnormal skeletal conditions.

Arthritis↗

Spermine oxidation products are selectively toxic to fibroblasts in cultures of normal human prostatic epithelium.

Contamination with fibroblasts has been a major problem in the isolation and establishment of pure cultures of prostatic epithelium, when developing in vitro cell models for studies on carcinogenesis. Addition of spermine to culture media containing fetal bovine serum results in oxidation of spermine to unstable aminoaldehydes which decompose releasing stable acrolein. This oxidation is catalyzed by amine oxidase present in ruminant serum. Prostatic epithelial cells are resistant to these oxidation products at the levels of spermine used. However, these oxidation products are selectively toxic to normal prostatic fibroblasts, which can be eliminated from mixed cultures, and pure cultures of prostatic epithelial cells can thus be established.

Acrolein↗

Ornithine metabolism in normal subjects and patients with cancer.

The metabolism of L-(1-14C)ornithine monohydrochloride was monitored in patients with histologically proven cancer and in normal volunteers. Following i.v. injection of 8 microCi C-14 ornithine (160 nmoles), the decarboxylation of ornithine--yielding 14CO2--was monitored for a 2.5-hr period using the ionization chamber and vibrating-reed electrometer of Tolbert, as modified by Davidson and Schwabe. Twelve normal subjects exhaled 7.3-15.7% of the administered C-14 (mean 12.6% s.d. 3.11%). In ten patients tested before initiation of therapy, recovery ranged from 18.2-32.1% (mean 23.02%, s.d. 4.52%). A t-test indicates a confidence level of > 99.5% that a significant difference exists between the two means. Re-testing of two normal volunteers showed little or no change in ornithine metabolism over a 2-5-mo period. Results from testing three cancer patients before and after therapy correlate well with clinical evidence of the presence of tumor burden.

Adult↗

Normal and benign human prostatic epithelium in culture. I. Isolation.

Isolation of normal human glandular epithelia and their growth and maintenance in vitro have been major problems. The primary objective of studies presented here was to isolate postpubertal, normal human, viable prostatic epithelium for in vitro cultivation. The long-term objective of these investigations was to develop an in vitro human cell model system for studies on prostatic carcinogenesis. A method for isolation of viable, normal and benign human prostatic epithelium, using collagenase for tissue dissociation, is described. Intact acini were isolated, which, on plating gave rise to vigorously growing monolayer cultures of epithelial cells. The purity of epithelial cultures partly depended upon the source of tissue. Specimens of normal prostate and those of benign tissue derived from open prostatectomies provided primarily pure epithelial cultures with occasional fibroblast colonies in some cultures, which could be removed. Cultures from some specimens of transurethral resection of the prostate (TURP) contained many fibroblast colonies due to incomplete separation of acini from the stroma. This resulted from incomplete digestion of denatured tissue caused by electrocauterization during surgery. Cultures established in this manner are being used to study the effects of hormones, vitamins and other growth regulators in order to establish growth requirements of these cells in vitro, which would facilitate their long-term maintenance.

Cell Division↗

Ornithine as a possible marker of cancer.

The nonprotein amino acid ornithine is the major source of polyamines in mammalian physiological systems. Increased urinary polyamine levels have been demonstrated in humans with varied types of cancers. The metabolism of DL-[1-14C]ornithine monohydrochloride in rats with either Walker 256 carcinoma or chemically induced methylcholanthrene tumors was studied. Following the i.p. injection of 3 muCi[14C]ornithine per 100 g body weight, the decarboxylation of ornithine-yielding 14CO2 was monitored by utilizing the vibrating reed electrometer-ionization chamber model of Davidson and Schwabe. Tumor-bearing animals showed significant increases in ornithine metabolism as compared to controls; for Walker 256 the tumor-bearing animal to control ratio rose from 1.16 to 1.78, for methylcholanthrene implants it rose from 1.19 to 1.82, and for methylcholanthrene paintings it rose from 1.00 to 2.20. With tumor regression ornithine levels of metabolism in the tumor-bearing animals returned to base line or nearly base-line levels. These results encourage us in our attempt to develop ornithine as a biological marker of cancer.

Animals↗