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Biomedical subjects

P F Schellhammer

Publications and source records attributed to P F Schellhammer.

At least 19 recordsLinked to original sources

Failure of anticytokeratin 18 antibody to improve flow cytometric detection of bladder cancer.

BACKGROUND: Bladder washing specimens containing inflammatory or squamous cells have been difficult to accurately analyze with single-parameter DNA flow cytometric (FCM) methods. METHODS: The anticytokeratin 18 antibody, CK5, was used in a multiparameter assay of 275 bladder washing and voided urine specimens to immunoselect only the bladder transitional cells for DNA analysis. RESULTS: Flow cytometric detection of transitional cell carcinoma was increased by immunoselection of CK5-positive cells in specimens from patients with disease. Unfortunately, a similar increase in hyperdiploid cells in pathologically benign specimens was observed, which resulted in a false-positive rate of 45%. In some instances, multiparameter FCM assays with CK5 could detect aneuploid cell populations not clearly evident by single-parameter analysis. CONCLUSIONS: However, the results from this study of the hyperdiploid cell fraction showed that the increased sensitivity resulting from the use of CK5 was not clinically useful because of the decrease in specificity.

Animals

Analysis of prostatic tumor cultures using fluorescence in-situ hybridization (FISH).

Analysis of ten primary prostatic tumor cultures using fluorescence in-situ hybridization (FISH) with pericentromeric probes for chromosomes 7, 8, 10, 16, 17, and 18 revealed aneusomies in nine of these specimens. Classical cytogenetics by G-banding indicated that only four of those same ten specimens had any (but not consistent) clonal abnormalities. This preliminary study suggests that aneusomy is a common event in early-stage prostatic tumors, and also supports the notion that multiple chromosomes are involved. In combination with routine cytogenetic analysis, FISH is thus likely to be a powerful tool in the evaluation of prostatic cancer.

Chromosome Aberrations

The detection of prostate specific antigen, MHS-5, and other markers in invasive prostate cancer and seminal vesicle.

Prostate specific antigen (PSA) is the most useful serum marker for following the disease status of prostate cancer patients after therapy. While PSA is felt to be an organ specific marker, lack of PSA expression in the seminal vesicles has not been adequately established. MHS-5 is a monoclonal antibody which recognizes an epitope on seminal vesicle specific antigen. Our objectives were to define PSA expression by the seminal vesicles, to determine whether MHS-5 could serve as an adjunct in the diagnosis of seminal vesicles invasion by carcinoma of the prostate, and to determine whether carcinoma, having invaded seminal vesicles would retain its expression of PSA and other prostate markers. Using an immunoperoxidase procedure, we studied thirteen seminal vesicles without histologic evidence of prostate cancer invasion and five seminal vesicles with locally invasive cancer. No seminal vesicles expressed PSA, whereas prostate cancer invading the seminal vesicles expressed PSA in all cases. MHS-5 expression was more variable. Only two of five cases of locally invasive tumor demonstrated seminal vesicles expression for MHS-5. Our findings further support the specificity of PSA. While MHS-5 may be helpful in delineating seminal vesicles in some instances, it is not a consistently reliable marker.

Antibodies, Monoclonal

Two-site monoclonal antibody-based immunoradiometric assay for measuring prostate secretory protein in serum.

We developed a double-determinant immunoradiometric assay for measuring serum prostate secretory protein (PSP), using monoclonal antibodies (MAb) against two different epitopes: MAb PSP-19 was the capture antibody and MAb PSP-6 was the tracer antibody. Assay sensitivity was 0.1 microgram/L. Analytical recovery of PSP was 93.5-104.6%, whereas the intra- and interassay mean CVs were 4.2% and 6.9%, respectively. In 92 normal men, ages greater than 50 years, the mean PSP concentration was 5.7 micrograms/L, with 10 (10.9%) men having concentrations greater than 10 micrograms/L. In contrast, 20 of 49 (40.8%) patients with benign prostate hyperplasia (BPH; mean PSP concentration 9.4 micrograms/L) and 46 of 100 (46%) patients with prostate cancer (mean PSP concentration 22.2 micrograms/L) had PSP concentrations greater than 10 micrograms/L. Mean serum PSP concentrations of the BPH (P less than 0.05) and prostate cancer (P less than 0.01) groups were significantly different from those of age-matched normal men. In a small group of patients, serial PSP concentrations correlated with the clinical course during therapy. Thus, PSP may be a useful marker for evaluating patients with prostate cancer.

Antibodies, Monoclonal

A novel prostate carcinoma-associated glycoprotein complex (PAC) recognized by monoclonal antibody TURP-27.

A prostate carcinoma-associated antigen recognized by MAb TURP-27 was characterized immunohistochemically and biochemically. TURP-27 antigen was found localized in the cell membrane and cytoplasm of the ductal epithelial cells of normal (10%), benign (75-100%) and malignant (20-100%) prostate cells. Fetal prostate tissues were also found to express the TURP-27 antigen, suggesting expression early in development. This antigen was not expressed by non-prostate tumors examined, but significant cross-reactivity was observed in myelinated nerves while minor cross-reactivity was seen in certain lymphocyte subsets, cells in the adrenal medulla and chief cells of stomach. Immunoblotting and biochemical data demonstrated that the TURP-27 antigen is a sialic-acid-containing glycoprotein complex with major molecular species in prostate tissues of 310-250, 180, 140, 115, 95-90, 69, and 40- to 35-kDa. Immunoblotting patterns similar to those observed for prostate tissues were also seen in CNS extracts with the exception of the 69 and 40- to 35-kDa proteins. This prostate carcinoma-associated sialoglycoprotein complex (PAC) recognized by MAb TURP-27 is likely to represent a novel tumor antigen expressed by prostate tumors.

Adenocarcinoma

Monoclonal antibody PD41 recognizes an antigen restricted to prostate adenocarcinomas.

A monoclonal antibody (MAb) designated PD41 (IgG1k) was generated by hyperimmunizing BALB/c mice with a membrane preparation prepared from a moderately to poorly differentiated prostate carcinoma surgical specimen. The immunohistochemical reactivity of MAb PD41 was shown to be highly restricted to the ductal epithelia and secretions of prostate adenocarcinoma tissues. Sixty-five % of the prostate tumor specimens were stained with MAb PD41, whereas no staining of the fetal or benign prostate specimens was observed. PD41 reacted minimally with normal prostate tissues, with less than 1% of the epithelial cells staining. This MAb did not react with nonprostate carcinomas or to a variety of normal human tissues. Using both radioimmunoassay and immunofluorescent procedures, several cultured human tumor cell lines, human blood cells, and purified antigens to prostate-specific antigen and prostatic acid phosphatase also were found not to express the PD41 antigen. MAb PD41 also was shown to bind to the target antigen present in seminal plasma obtained from prostate carcinoma patients but not to seminal plasma from normal donors. Immunoblots of gel-separated components of prostate carcinoma tissue extracts indicate that the molecular weight of the proteins carrying the PD41 antigenic determinant can differ among individual tumors, ranging from Mr 90,000 to greater than 400,000. However, in seminal plasma from prostate cancer patients, the predominant component recognized by PD41 is the diffuse Mr greater than 400,000 band. It appears that this monoclonal antibody may recognize a prostate carcinoma-associated mucin-like antigen, which is preferentially expressed on prostate carcinomas, and therefore, may be a useful marker to distinguish benign prostate hyperplasia from prostate carcinoma.

Adenocarcinoma

Prostate specific antigen levels after definitive irradiation for carcinoma of the prostate.

Prostate specific antigen (PSA) levels were determined in 78 patients judged clinically to be free of disease at intervals of 36 or more months (range 38 to 186 months, median 87 months) after completion of irradiation therapy by 125iodine implantation or external beam radiation. Of this select group of patients 38% had undetectable serum PSA levels (0.5 ng./ml. or less) and 38% had PSA levels that were within normal limits (4.0 ng./ml. or less). All stages and grades were represented. Undetectable PSA levels were only rarely found (3%) in patients with carcinoma of the prostate before treatment. In 24 of these 78 patients a negative biopsy of the irradiated prostate had been obtained 18 to 42 months after treatment. When the PSA level was drawn, which ranged from 7 to 16 years after treatment, an equal percentage of these biopsied patients had either an undetectable, normal or elevated level. Irradiation is able to decrease PSA to undetectable levels in some patients with prostatic carcinoma. Whether this reflects suppression of marker production alone or, more importantly, ablation of prostate cancer producing that marker remains to be determined.

Acid Phosphatase

Hemibody irradiation in advanced prostatic carcinoma.

In summary, hemibody irradiation has developed as a safe, efficient technique for palliating multiple sites of symptomatic osseous metastases, which occur so often in advanced prostatic carcinoma. The rapidity, frequency, and duration of pain relief, as well as the convenience to the patient of a solitary treatment to multiple symptomatic areas simultaneously, make this type of treatment especially appealing. By following premedication and radiation dose guidelines, both acute and delayed side effects can be kept tolerable or at a minimal incidence. Although sequential hemibody radiation has also been explored as "systemic" therapy, the results in prostatic carcinoma have not proved dramatic, and complications have been considerable. Hormonal therapy would certainly seem to be less life-threatening and equally beneficial according to present data. As a palliative treatment, however, hemibody irradiation is a pragmatic option for relieving prostatic cancer pain.

Bone Neoplasms

Flow cytometric DNA analysis after immunoselection of bladder tumor cells with monoclonal antibody DU83.21.

Adequate preservation of neoplastic cells and the elimination of interference by inflammatory cells in measuring tumor cell DNA content represent two important objectives necessary for accurate flow cytometric analysis of bladder carcinomas. An experimental model consisting of a mixture of cultured bladder carcinoma cells (T24) and human buffy-coat (BC) cells was used to evaluate various preservatives and an anti-bladder carcinoma monoclonal antibody (MoAb), DU83.21, for separating inflammatory cells (BC cells) from T24 cells. A final concentration of 25% ethanol was found to be the most effective preservative of several tested. After incubation with the MoAb DU83.21 and propidium iodide (DNA stain), the T24 cells could be separated from the BC cells, permitting accurate DNA analysis of the tumor cells. Application of this system to specimens from bladder cancer patients enhanced the detection and DNA analysis of the tumor cell populations.

Aneuploidy

Leukocyte migration inhibition assay in patients with bladder cancer.

The leukocyte migration inhibition assay has demonstrated successfully tumor-associated antigenic activity in protein extracts of cell culture lines of a number of neoplasms. Our data have shown a high degree of leukocyte migration inhibition reactivity with protein extracts from the well characterized T-24 transitional carcinoma cell line. Thus, the leukocyte migration inhibition assay may prove a valuable method of in vitro assessment of the cell-mediated immunity of bladder cancer patients and as a method to monitor attempts at further purification of tumor-associated antigens.

Antigens, Neoplasm

Primary mucus-secreting adenocarcinoma of the renal pelvis.

Mucus-secreting adenocarcinoma of the renal pelvis is an extremely rare tumor. It arises from multipotential transitional epithelium which is capable of undergoing metaplastic transformation when subjected to chronic irritation from calculi, hydronephrosis, or pyelonephritis. Women are affected slightly more often than men. Tumor invasion implies a poor prognosis. Long-term survival occurs but is infrequent. In the case reported, preoperative angiography yielded useful diagnostic information.

Adenocarcinoma, Mucinous

Pathological findings after preoperative irradiation for carcinoma of the urinary bladder.

Pathological descriptions of specimens obtained in 17 patients with urinary bladder carcinoma both at biopsy before preoperative irradiation and after surgery are presented. No positive lymph nodes were found in 16 patients who had lymphadenectomy at the time of surgery. No tumor was found postoperatively in 58.8% of patients and 82.3% had a reduction in tumor stage.

Adult

Kidney neoplasms.

The author reviews the diagnosis and treatment of carcinoma of the kidney. Surgery remains the most effective therapy. The management of metastatic disease is discussed.

Adenocarcinoma

Cell-mediated immunity in patients with renal cell carcinoma as measured by leukocyte migration inhibition test.

The cell-mediated immune (CMI) response to tumor-associated antigens present in 3 M KCL extracts of renal cell carcinoma tissue was measured in patients with renal cell carcinoma (RCC) by the leukocyte migration inhibition (LMI) test. Of 30 patients with histologically proved RCC, 19 (63%) gave a positive LMI test; whereas, 2 of 28 (7%) of the normal donors, 13 of 43 (30%) patients with other cancers, and 5 of 14 (36%) benign kidney disease patients gave positive tests. Thirteen per cent of RCC patients reacted to a normal kidney extract. Although 33% gave a positive response to a lung carcinoma extract, the incidence of reactivity was less than that observed with the lung cancer patients. These results suggest that a CMI response to a renal carcinoma-associated antigen was measured by the LMI test. Correlation of the LMI data with the stage of disease and clinical status indicated that 71% of patients that had a localized tumor and were clinically free of disease one year postnephrectomy lost their tumor-directed CMI response. Patients with distant metastasis (Stage D) were LMI positive provided they had not received radiation or hormone therapy at the time of testing. These results suggest that the demonstration of CMI, as measured by the leukocyte migration inhibition test, correlates with the presence of active disease.

Adenocarcinoma

Bilateral testicular rupture: report of a case with an unusual presentation.

A case of bilateral testicular rupture after blunt trauma is presented. It is unusual in that the patient presented with a unilateral retractile testis with pain. The contralateral testis was asymptomatic but was found to be ruptured at exploration. The objectives of preservation of testicular function and prevention of misdiagnosis and undiagnosed cases are reiterated. Early exploration of all blunt trauma to the scrotum and testis is advocated. The surgical management of the ruptured testis is reviewed with regard to orchiectomy, primary closure, closure with portion of tunica vaginalis and decompression of the contused testis.

Adult