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Biomedical subjects

M M Webber

Publications and source records attributed to M M Webber.

At least 19 recordsLinked to original sources
PubMed1991

Retinoids enhance lectin binding to gp130, a glycoprotein of NIH-3T3 cells: correlation with cell growth and adhesion.

Our previous work has shown that retinoic acid (RA) enhances fibroblast cell attachment to plastic and to laminin. The treatment of NIH-3T3 cells with RA for 2 days also caused a reproducible increase in the binding of the lectin Phaseolus vulgaris leukoagglutinin (PHA-L) to a glycoprotein of molecular weight 130,000 (gp130) as judged by SDS-PAGE analysis. This finding is consistent with an increased number of beta-1,6-linked N-acetylglucosaminyl residues on gp130. Of the 11 additional lectins tested Ricinus communis agglutinin I (RCA), Phaseolus vulgaris erythroagglutinin (PHA-E), soybean agglutinin (SBA), and succinylated wheat germ agglutinin (sWGA) showed a significant increase in binding specifically to gp130. Similar to RA, 13-cis-RA and 3,5-di-tert-butyl-4-chalcone carboxylic acid, a synthetic retinoid, also increased PHA-L binding to gp130; they also enhanced cell adhesiveness and inhibited cell growth. N-(4-Hydroxyphenyl)-all-trans-retinamide and thyroxine failed to influence adhesion and did not increase PHA-L binding to gp130. Moreover these compounds also failed to inhibit cell growth and to alter the morphology of the cultured cells. Since trypsin is utilized to remove cells from the culture dishes before they are used in the attachment assay to laminin, we studied the effect of this trypsinization step on PHA-L binding to gp130. Trypsin reduced PHA-L binding thus suggesting cell surface localization of gp130. After trypsin treatment RA-treated cells still showed enhanced PHA-L binding compared to dimethyl sulfoxide (DMSO) control. In conclusion RA-induced cell adhesiveness and growth inhibition are accompanied by an increase in the PHA-L, PHA-E, SBA, RCA, and sWGA binding to gp130. The sensitivity of gp130 to trypsin suggests that it is a cell surface glycoprotein.

Animals↗
PubMed1990

Indium-111 white blood cell scans: sensitivity, specificity, accuracy, and normal patterns of distribution.

The UCLA Hospital experience with indium-111 labeled white blood cells was reviewed. There were a total of 345 consecutive cases covering a broad range of clinical indications. The overall sensitivity of the method was 79%, specificity was 62%, and accuracy was 73%. The sensitivity for suspected osteomyelitis cases was 84%, with a specificity of 65% and an accuracy of 75%. For other cases sensitivity was 77%, specificity was 60%, and accuracy was 72%. Furthermore, patterns of normal distribution were reviewed.

Bacterial Infections↗
PubMed1990

Comparison of Biello, McNeil, and PIOPED criteria for the diagnosis of pulmonary emboli on lung scans.

The McNeil, Biello, and newly proposed PIOPED (from the National Institutes of Health-sponsored study, Prospective Investigation of Pulmonary Embolism Detection) interpretive methods for detection of pulmonary embolism on lung scans were compared in 96 patients who also underwent pulmonary angiography. Segmental findings on 99mTc perfusion and aerosol ventilation scans, chest radiographs, and pulmonary angiograms obtained within 48 hr of each other were encoded along with other information into a data base to facilitate analysis. The McNeil, Biello, and PIOPED criteria were applied to the encoded data. Although the PIOPED set of criteria yielded the most favorable likelihood ratio for predicting an angiogram showing pulmonary emboli and a favorable likelihood ratio for predicting an angiogram not showing pulmonary emboli, it had the highest number of indeterminate studies. The McNeil criteria demonstrated the least favorable likelihood for predicting pulmonary emboli on an angiogram. The Biello and McNeil criteria showed the most favorable likelihood ratio for predicting an angiogram not showing pulmonary emboli. Analysis of receiver-operating-characteristic (ROC) curves yielded the greatest area under the ROC curve for the Biello criteria, but there were no statistically significant differences among the three sets of criteria. This study suggests that the Biello scheme represents the best compromise of the sets of criteria studied.

Angiography↗
PubMed1988

Metallothionein induction and deinduction in human prostatic carcinoma cells: relationship with resistance and sensitivity to adriamycin.

Human prostate carcinoma cell line DU-145 was used to examine the relationship between the intracellular levels of cysteine-rich metallothionein (MT) and the sensitivity or resistance of cells to Adriamycin (ADR). The basis for the poor response of human prostate carcinomas to ADR was studied. Cadmium-resistant (Cdr) cells, capable of growth in 10(-5) M cadmium, were derived from DU-145 cadmium-sensitive (Cds) cells, by exposure to increasing concentrations of cadmium. The relative rates of MT synthesis were measured by L-[35S]cysteine incorporation and MT separation by high-performance liquid chromatography. Cdr cells, continuously exposed to cadmium, show a steady-state rate of MT synthesis (designated as control = 100%) which is 3.5 times the basal rate in Cds cells (29%). Dose-response curves, using clonal and cell count assays, show that the dose levels required to produce inhibition of growth to 50% and 90% of control, respectively, of ADR for Cdr cells (19.00 and 132.0 ng/ml) are 1.5 to 1.7 times those for Cds cells (12.5 and 77.5 ng/ml). In the absence of cadmium, deinduction of MT occurs with MT synthesis declining, after 70 and 118 h, to 29% and 19% of control. Correspondingly, in such deinduced cells (Cdr minus cadmium), the 50% inhibitory doses of ADR in clonal and growth assays are 3.5 and 4.8 ng/ml, respectively. Thus, deinduced cells are 3 and 4 times more sensitive to ADR than Cds and Cdr cells. This increased sensitivity is explained by the rapid and marked inhibition of MT synthesis upon exposure to ADR, even in the presence of cadmium, so that after 6 and 10 h in the presence of 10 ng/ml of ADR, the rates drop to 62% and 19% of control. On the basis of these results, we propose that: (a) the increased levels of MT increase the resistance of Cdr cells to ADR and that this may be partly responsible for the poor response of prostate carcinomas to ADR; (b) MT deinduction results in increased sensitivity to ADR; and (c) ADR inhibits MT synthesis. Thus, it is suggested that a treatment regimen consisting of ADR exposure followed by a second exposure, during increased ADR sensitivity, may be effective for growth inhibition of slow-growing prostatic carcinomas.

Cadmium↗
PubMed1987

Pulmonary leukosequestration without hypoxemia during hemodialysis.

Dialysis-associated hypoxemia is frequently of clinically significant magnitude and is incompletely understood. In order to investigate the hypoxemia directly we labelled a patient's white blood cells with 111Indium-oxine prior to hemodialysis with acetate or bicarbonate baths. Both dialysate buffers were associated with similar degrees of early peripheral neutropenia, complement activation and elevation of lactoferrin levels, with simultaneous lung localization of radionuclide activity. However, there was not widening of the alveolar to arterial oxygen gradient, or increased wasted ventilatory fraction during this early time period. Significant hypoxemia occurred later in the dialysis, was associated with a decreased respiratory exchange ratio and only occurred with the acetate dialysate buffer. Thus, initial pulmonary leukosequestration was documented but did not have an adverse impact on gas exchange. Hypoxemia during acetate dialysis occurred instead as a consequence of alveolar hypoventilation.

Humans↗
PubMed1987

Evaluation of musculoskeletal sepsis with indium-111 white blood cell imaging.

The detection of musculoskeletal sepsis, especially following joint replacement, continues to be a challenging problem. Often, even with invasive diagnostic evaluation, the diagnosis of infection remains uncertain. This is a report on the first 55 Indium-111 white blood cell (WBC) images performed in 39 patients for the evaluation of musculoskeletal sepsis. There were 40 negative and 15 positive Indium-111 WBC images. These were correlated with operative culture and tissue pathology, aspiration culture, and clinical findings. Thirty-eight images were performed for the evaluation of possible total joint sepsis (8 positive and 30 negative images); 17 for the evaluation of nonarthroplasty-related musculoskeletal sepsis (7 positive and 10 negative images). Overall, there were 13 true-positive, 39 true-negative, two false-positive, and one false-negative images. Indium-111 WBC imaging is a sensitive and specific means of evaluating musculoskeletal sepsis, especially following total joint replacement.

Adult↗
PubMed1986

Tumor uptake of 5-fluorouracil, methotrexate, and adriamycin vs gallium.

Since the imaging pattern of 67Ga-citrate is well known, it can be the benchmark for evaluation of potential tumor imaging agents. Tritium labeled 5-fluorouracil, Adriamycin, (doxorubicin/Adria) and Methotrexate/Lederle were compared at 2 h to 67Ga-citrate at 2 and 48 h by percent uptake per gram of various tissues and tumor in rats implanted with Walker 256 carcinosarcoma. 67Ga at 48 h showed approximately three times more uptake in the tumor than 5 fluorouracil and eight times more than the others. 5 Fluorouracil showed approximately three times greater uptake than Methotrexate or doxorubicin and 1.4 times the 2 h uptake of 67Ga. 5 Fluorouracil shows potential as an imaging agent especially where the waiting time between injection and imaging must be short.

Animals↗
PubMed1986

Vitamin E enhances the chemotherapeutic effects of adriamycin on human prostatic carcinoma cells in vitro.

Vitamin E (tocopherol) enhances the growth inhibitory effects of adriamycin (ADR) on a variety of cancer cells in vitro. The role of vitamin E (d-alpha-tocopheryl) acid succinate in adjuvant chemotherapy with ADR was assessed in DU-145 human prostatic carcinoma cells in culture. Adriamycin produced a dose-dependent growth inhibition of DU-145 cells. The ID50 of DU-145 cells on the criteria: of clonal assay was 13 ng./ml. and of cell count assay was 14 ng./ml. Vitamin E succinate also inhibited the growth of DU-145 human prostatic carcinoma cells in a dose-dependent manner. 4.4 micrograms./ml. and 5.4 micrograms./ml. vitamin E succinate in the culture medium produced inhibition of growth to 50 per cent of control (ID50) in the clonal and the cell count assays respectively. When adriamycin and vitamin E succinate were used in combination, both additive and synergistic effects were observed, depending on the concentration of vitamin E succinate used. Doses of vitamin E succinate greater than its ID50 had a synergistic effect while doses smaller than its ID50 had an additive effect. In either case, the presence of vitamin E succinate caused an enhancement of tumor cell cytotoxicity of adriamycin while decreasing its ID50. Equivalent concentrations of sodium succinate and ethanol used to dissolve vitamin E succinate did not have any effect on DU-145 cells. Thus, it is concluded that the effect of vitamin E succinate is due to vitamin E and not due to succinate or ethanol. These results suggest that vitamin E may have a role in the treatment of human prostatic cancer as an adjuvant agent to adriamycin.

Adenocarcinoma↗
PubMed1985

Inhibitory effects of selenium on the growth of DU-145 human prostate carcinoma cells in vitro.

The growth of DU-145 human prostate carcinoma cells is reduced to 50% of control by 1 X 10(-6) M to 2 X 10(-6) M selenium and to 2% of control at 10(-4)M selenium. These cells show greater sensitivity to inhibition of growth or DNA synthesis by selenium than human W1-38 and HeLa cells and mouse mammary tumor cells. It has been shown that selenium inhibits carcinogenesis and reduces the incidence of chemical carcinogen and virus-induced tumors of a variety of organs in animals. Selenium may also inhibit the growth of certain tumor cells of non-human origin. To our knowledge, this is the first study on the effects of selenium on the growth of human tumor cells. From extrapolation, it is deduced that selenium serum levels in humans living in high selenium areas may be as high as 10(-6) M and could be effective in inhibiting the growth of tumor cells in vivo. These findings have implications in the prevention and intervention of prostate cancer in man.

Animals↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1979

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↗
PubMed1978

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↗