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Biomedical subjects

R A Stephenson

Publications and source records attributed to R A Stephenson.

At least 55 records · Page 3Linked to original sources
PubMed1992

Prognostic significance of antigenic heterogeneity, Gleason grade, and ploidy of lymph node metastases in patients with prostate cancer.

We retrospectively evaluated 51 prostate cancer patients found to have pelvic lymph node metastases at the time of pelvic lymphadenectomy and 125I implantation. All of them were followed until death or for a minimum of 70 months. Rabbit polyclonal anti-PSA, anti-PAP, anti-PSP-94, and mouse TURP-27 monoclonal antibodies were used in immunohistochemical evaluation of the metastatic lesions. In addition, Gleason grade and ploidy were assessed and correlated. No tumor with a Gleason grade of less than 7 could be found in the metastatic lymph nodes. Time to progression (P = .003), disease-specific survival (P = .009), and overall survival (P = .003) were significantly shorter in patients whose tumors had a primary Gleason pattern of 5 (grade 9 or 10). In the PSA study, patients whose tumors were reactive in more than 75% of cancer cells experienced significantly longer survival than those with less than 75% of cancer cells expressing PSA (P = .0006 log rank test). The means of overall survival +/- SEM were 71.5 +/- 5.0 and 34.9 +/- 5.4 months, respectively. Similar correlations were found with disease-specific survival and time to progression. Patterns of PAP expression and TURP-27 reactivity were not prognostically useful, whereas PSP-94 expression may add some additional information. These data suggest that evaluation of tissue PSA heterogeneity in lymph node metastases may offer additional prognostic information on prostate cancer patients. Better prediction of individual prognosis may be possible with the combined use of Gleason grade, flow cytometry, and PSA expression.

Adult↗
PubMed1991

Fibrin glue for partial nephrectomy.

Fibrin glue, a mixture of concentrated autologous fibrinogen and bovine-derived thrombin, was used to achieve hemostasis during 7 partial nephrectomies. After transected vessels were suture ligated, topically applied fibrin glue filled all renal defects with an adherent clot that resulted in immediate hemostasis. There was no case of delayed hematoma or abscess formation, and no complications were referrable to the use of fibrin glue. Although fibrin glue is no substitute for early vascular control and careful surgical technique, its ability to stop venous oozing from the cut surface of renal parenchymal tissue dramatically facilitates hemostatic control.

Fibrin Tissue Adhesive↗
PubMed1991

Prostate specific antigen in patients with clinical stage C prostate cancer: relation to lymph node status and grade.

The preoperatively drawn sera from 84 previously untreated patients who had clinical stage C prostate cancer and underwent staging pelvic lymph node dissections were sent for monoclonal Hybritech analysis to assess the usefulness of prostate specific antigen (PSA) in predicting lymph node status. Of the 84 patients 47 (56%) had positive lymph nodes at surgery. The median PSA value for all patients with nodal metastases was 11.4 ng/.ml., and for those without it was 11.2 ng./ml. Relative to Gleason score, median PSA values were 11.35 for 2-4, 12.2 for 5-7 and 10.9 ng./ml. for 8-10. Within each M.D. Anderson grade median PSA values were 10.15 for grade I, 13.2 for grade II, 12.7 for grade III and 10.5 ng./ml. for grade IV. Simultaneously drawn preoperative frozen serum samples for 28 of these patients were independently analyzed by the Yang radioimmunoassay. Comparing Hybritech and Yang methods revealed strong statistical co-association (correlation coefficient R2 = 97.36, p less than 0.00001) but neither assay was statistically associated with nodal metastasis. Although no PSA level excluded the presence of nodal disease, we suggest that a Hybritech PSA of greater than 30 ng./ml. and a Yang PSA of greater than 50 ng./ml. may serve as a weak adjunctive marker predicting nodal metastasis.

Adenocarcinoma↗
PubMed1991

Surveillance for clinical stage I nonseminomatous testis carcinoma: rationale and results.

Surveillance protocols for clinical stage I nonseminomatous germ cell tumors of the testis have demonstrated that using current staging methods, approximately 75% of clinical stage I patients can be cured with orchiectomy alone. With treatment of patients who relapse, the overall outcome with surveillance is similar to that of standard therapy. Retrospective analysis of clinical and pathologic parameters appears to identify a subgroup of patients with a very low risk of relapse. If confirmed in prospective studies, this low-risk group will be well suited for orchiectomy with subsequent observation. The remainder of patients have an intermediate (40-60%) risk of relapse. How these remaining patients are best managed is a subject of controversy. The resolution of this controversy will likely require substantial improvement in the methods for predicting relapse, or substantial reductions in the patient burden of surgical and chemotherapeutic treatment.

Humans↗
PubMed1991

Ratio of polyclonal-monoclonal prostate-specific antigen levels. Discrimination of nodal status in prostate tumors that produce low marker levels.

The preliminary data we present in this report suggest that the ratio of polyclonal-monoclonal serum prostate-specific antigen levels may add clinically useful information to that obtained using serum prostate-specific antigen levels alone. We hypothesize that the diversity of prostate-specific antigen ratios observed in our data reflects a diversity in the antigenic and structural attributes of prostate-specific antigen molecules found in the sera of patients with prostate cancer. Further, this heterogeneity of molecules is a reflection of the diverse and altered metabolic state of human prostate cancer and appears to be related to biologic behavior in individual patients.

Antibodies↗
PubMed1991

An image analysis method for assessment of prognostic risk in prostate cancer: a pilot study.

Fully automated computerized image analysis at medium resolution (1 micron per pixel space) was applied in a study of 17 patients with stage D1 prostate cancer. For this pilot study, patients were selected on the basis of very good or very poor outcome. This selection was made in the hope of identifying morphometric features that are useful in prognostic assessment. Nine patients with good outcome were alive after 7 or more years of follow-up and eight patients with poor prognosis were dead of disease in less than 3 years. All patients were treated with 125I seed implantation to the prostate and pelvic lymph node dissection. Hormone therapy was not administered until the time of distant failure. Routine hematoxylin and eosin tissue sections of lymph nodal tissue bearing metastatic neoplasm were used for this analysis. A minimum of eight scenes per case was analysed. Of 50 measured parameters on each cluster, five (gray level distribution, number of cell clusters per scene, bending energy, average cluster area and cluster polarity) were useful to distinguish patients with good outcome from those with a poor outcome. Thirteen of the 17 patients were correctly classified by image analysis (P = 0.044, Fischer's exact test). By comparison, flow cytometry of the identical tissue samples correctly classified 14 of 17 patients (diploid, good outcome; aneuploid, poor outcome; P = 0.009). Only one patient was incorrectly classified by both image analysis and flow cytometry, implying a complementary prognostic role for the two methods. The encouraging result, successful identification of useful morphometric features, justifies a larger study of unselected patients.

DNA↗
PubMed1989

Computerized microscopic analysis of prostatic fine needle aspirates. Comparison with breast aspirates.

Computerized image analysis was employed to analyze fine needle aspiration smears of the prostate and breast using both high-resolution images of individual cells and medium-resolution images of scenes and clusters (contextual analysis). A linear discriminant analysis was used to demonstrate the computer's ability to discriminate between benign and malignant categories for both types of tissue. Correct classification as benign or malignant using contextual analysis was achieved in 22 of 26 prostatic aspirates and in 15 of 18 breast aspirates, as determined by comparison with histology. The addition of high-resolution single-cell analysis resulted in correct classification of 24 of 26 prostatic aspirates and all breast aspirates. For virtually all features, the distinction between benign and malignant was more subtle for prostatic than for breast tissue. The data indicate that contextual analysis may be less effective as an adjunct to high-resolution single-cell microscopy of prostatic specimens than it is for breast specimens.

Biopsy, Needle↗
PubMed1988

Inhibitors of cyclic AMP phosphodiesterase. 3. Synthesis and biological evaluation of pyrido and imidazolyl analogues of 1,2,3,5-tetrahydro-2-oxoimidazo[2,1-b]quinazoline.

Hybridization of structural elements of 1,2,3,5-tetrahydro-2-oxoimidazo[2,1-b]quinazoline ring system common to the cyclic AMP (cAMP) phosphodiesterase (PDE) inhibitors lixazinone (RS-82856, 1) and anagrelide (3) with complementary features of other PDE inhibitor cardiotonic agents prompted the design and synthesis of the title compounds 7a-d, 11, 12, and 13a,b. The necessary features of these compounds were determined within the framework of the proposed active-site models for the high affinity form of cAMP PDE inhibited by cGMP (type IV). Evaluation of these targets, both in vitro as inhibitors of platelet or cardiac type IV PDE or in vivo as inotropic agents in the pentobarbital-anesthetized dog model of congestive heart failure, showed that these structure possessed negligibly enhanced activities over the parent heterocyclic system, and remained significantly inferior to 1 in all respects. This difference is ascribed to the absence of the N-cyclohexyl-N-methylbutyramidyl-4-oxy side chain of 1. The proposal that the acidic lactam-type functionality, common to the type IV PDE inhibitor inotropic agents such as 4-6 and 8-10, mimics the polarizable cyclic phosphate moiety of cAMP suggested that the side chain of 1 may function as an effective surrogate for selected characteristics of the adenine portion of cAMP. However, the results of this study show that incorporation of adenine-like hydrogen-bonding functionalities common to other type IV PDE inhibitors into the 1,2,3,5-tetrahydro-2-oxoimidazo[2,1-b]quinazoline system did not enhance activity to the levels observed for 1 and analogues. These observations, coupled with the kinetic pattern of inhibition of type IV PDE observed for 1 and analogues, suggest that access to a secondary, lipophilic-tolerant binding site, possibly coincident with the adenine binding domain, and adjacent to the catalytic ribose-phosphate binding site of platelet and cardiac type IV PDE, is responsible for the increased potency of these compounds.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1988

Flow cytometry in genitourinary malignancies using paraffin-embedded material.

This review summarizes the current state of flow cytometric analysis of GU neoplasms using paraffin-embedded materials. Future investigation using this method should take advantage of the ability to examine laboriously generated clinical series retrospectively. It will be important for investigators to control for covariance of all other clinical parameters with multivariate analysis. In addition, patient groups preferably should be clearly and somewhat narrowly defined, and uniformly treated. From carefully performed studies we may learn ways in which flow cytometric measurements may be used to prognosticate with greater precision, and to more objectively stratify patients to appropriate treatments.

Adrenal Gland Neoplasms↗
PubMed1987

Flow cytometry of prostate cancer: relationship of DNA content to survival.

Between March 1970 and December 1978 there were 366 patients with prostatic cancer treated by 125I seed implants and pelvic lymph node dissection. All had a minimum of 5 years follow-up. One hundred thirty-three patients had metastatic prostatic cancer in lymph nodes (Stage D1) at the time of lymph node dissection and seed implantation. Ninety-one of the 133 patients were judged to have sufficient metastatic prostatic cancer in their nodal tissue (greater than 50% replacement with tumor) to justify flow cytometric cellular DNA measurements on the involved paraffin-embedded nodal tissue. Nine patients were excluded due to uninterpretable DNA histograms leaving 82 patients for analysis. Forty-nine patients had aneuploid and 33 had diploid tumors. There was no statistical bias between the aneuploid and diploid groups due to age (P = 0.970, chi 2 test), time between diagnosis and implantation (P = 0.217, chi 2 test), number of positive nodes (P = 0.669, two-sample t test of means), or tumor grade (P = 0.332, chi 2 test). Median survival time of the aneuploid and diploid groups was 5.0 and 8.8 years, respectively (P = 0.0109, log rank test). Cox regression analysis confirmed the effect of aneuploidy versus diploidy on survival by controlling for other potentially confounding variables (age, time from diagnosis to implantation, number of positive nodes, and grade). Grade as a predictor of survival did not approach statistical significance in this series of relatively small size (P = 0.116). Thirty-eight of the 82 patients had moderately differentiated neoplasms. Nineteen of these were aneuploid and 19 diploid. The median survival was 5.8 and 9.1 years, respectively, for these grade-matched aneuploid and diploid groups (P = 0.039, log rank test). We conclude that flow cytometric DNA measurements on archived paraffin-embedded tumor in nodal metastases appear to be a strong predictor of survival for Stage DI prostatic cancer.

Aneuploidy↗
PubMed1986

Effect of section thickness on quality of flow cytometric DNA content determinations in paraffin-embedded tissues.

DNA content determinations were carried out by flow cytometry on nuclear suspensions prepared from the same paraffin-embedded tissue block for each of eight surgically resected human carcinomas at section thicknesses of 5,10,20,30,40,50, and 100 millimicrons. Flow cytometric DNA determinations were also obtained on fresh tissue specimens in four of the eight carcinomas. As section thickness decreased below 50 millimicrons, there was a progressive increase in the histogram baseline noise at low DNA values and a decrease in the relative peak height of aneuploid DNA. The former was attributed to an increase of nuclear fragments in thinner sections, and the latter to the greater probability of transection of the larger aneuploid cells within a specimen. Both artifacts were minimized at section thickness of 50 millimicrons or greater.

Breast Neoplasms↗
PubMed1986

High energy shock waves suppress tumor growth in vitro and in vivo.

Exposure of the Dunning R3327AT-3 rat prostatic carcinoma and SK-Mel-28 human melanoma, in vitro, to high energy shock waves resulted in a reduction in cell viability as determined by trypan blue exclusion and a decrease in the number of colonies formed in a clonogenic assay. Flow cytometric determination of DNA content in R3327AT-3 cells treated in vitro indicated a selective diminution of cells in the G2 and M phases of the cell cycle. When R3327AT-3 cells exposed to high energy shock waves were subsequently injected into rats, or tumor bearing animals were treated by high energy shock waves targeted at the tumor, a delay in tumor growth was observed. These observations indicate that high energy shock waves are cytotoxic to tumor cells in vitro and in vivo. Additional research into the possible use of high energy shock waves in the non-invasive destruction of animal and human tumors is warranted.

Animals↗
PubMed1986

Flow cytometry in urologic oncology.

Flow cytometers have proved to be useful research tools in cellular biology. By using these devices, rapid and objective measurements of a variety of cellular parameters can be made on a cell-by-cell basis. The application of flow cytometers to the study of urologic neoplasms is at present very preliminary. The available literature on the flow cytometric study of urologic tumors is presented and discussed.

DNA, Neoplasm↗
PubMed1985

Diterpenoid sweeteners. Synthesis and sensory evaluation of stevioside analogues with improved organoleptic properties.

Congeneric series of stevioside (1) and rebaudioside A (3) analogues have been prepared. It was found that the bitter-taste component endogenous in the natural compounds 1 and 3 may be eliminated by increase in molecular hydrophilic character. Through the series of compounds prepared, bitter-taste character was correlated with k', a chromatographic indicator of gross hydrophilicity. An analogue (11) of stevioside, shown chromatographically to be of increased hydrophilicity, was prepared and found to exhibit no bitter-taste character. Similarly an analogue (13) of rebaudioside A, having increased polarity, was prepared and found not to exhibit any bitter taste. The rebaudioside A analogue 13 was determined to have higher potency than 11 is suggested as a potential non-nutritive sweetener for food applications.

Diterpenes↗
PubMed1985

Inhibition of mouse natural killer cell activity by zinc.

The effect of zinc on mouse natural killer (NK) cell activity was evaluated. The inhibition of NK cell activity with zinc was dependent on the concentration of zinc added (range tested: 0-40 micrograms zinc/ml) and occurred at both effector-to-target ratios tested. Zinc-induced inhibition of NK activity was observed with the use of peritoneal or splenic effector cells on Toxoplasma gondii-augmented NK activity. Maximal inhibition of activity was noted when zinc was present for the entire assay period. Inhibition was present but less marked with pretreatment of effector cells with zinc. Pretreatment of target cells with zinc had no measurable effect on NK cytotoxicity. Effector-to-target cell binding as measured by single-cell assays was not significantly altered by zinc. These results indicate that zinc is a potent inhibitor of NK activity.

Animals↗
PubMed1981

Dihydrochalcone sweeteners. A study of the atypical temporal phenomena.

Neohesperidin dihydrochalcone (NHDHC), known since 1963 as an intensely sweet compound, is determined to be 340 +/- 60 (p less than 0.05) times more potent than sucrose. The unusual temporal properties of this material are hypothesized as being due to the effects of metabolism, conformation, chelation, or hydrophobicity. Forty-four analogues are synthesized to test the four hypotheses, none of which are strongly supported. A method of quantitation of temporal characteristics of tastant molecules is developed so as to allow comparison of taste appearance time (AT) and extinction time (ET) of experimental compounds. Four of the new compounds, 40 and 43-45, exhibit high sweetness potencies, ranging from 280 and 440 times sucrose, and may be useful in selected food systems. The temporal taste characteristics remain unimproved over NHDHC, however.

Binding Sites↗