Biomedical subjects

J Fleischmann

Publications and source records attributed to J Fleischmann.

54 records · Page 3Linked to original sources

PubMed1985

Human renal cell carcinoma xenograft: morphology, growth and chemosensitivities.

A primary human renal clear cell carcinoma has been developed as a xenograft (JDF-1). Passage 7 of the JDF-1 tumor retained the microscopic morphology of the primary tumor, electron micrographs have confirmed its epithelial characteristics and karyotyping of a subsequent passage has proved it is not a murine hybrid. Immunoperoxidase studies using a panel of murine monoclonal antibodies demonstrate an antigenic phenotype specific for human renal cancer. In vitro chemosensitivities of the JDF-1 tumor were determined by the double-layer soft-agar clonogenic assay method. JDF-1 showed no significant sensitivities to several standard chemotherapeutic agents, but alpha-2-interferon and difluoromethylornithine in combination synergistically inhibited its growth by 74 per cent.

Aged↗

PubMed1984

Effects of alpha-difluoromethylornithine and recombinant interferon-alpha 2 on the growth of a human renal cell adenocarcinoma xenograft in nude mice.

The effects of human recombinant interferon-alpha 2 (IFN-alpha 2) and alpha-difluoromethylornithine (DFMO) as single agents and in combination were studied for efficacy against the renal cell adenocarcinoma (JDF-1) in an in vitro clonogenic assay and in vivo as xenografts in nude mice. In vitro studies showed dose-dependent inhibition of JDF-1 colony formation by IFN-alpha 2. DFMO alone did not significantly inhibit colony formation even though ornithine decarboxylase activity was significantly inhibited. The combination of IFN-alpha 2 and DFMO synergistically inhibited JDF-1 colony formation. The synergism was more readily observed at low IFN-alpha 2 concentrations. In vivo studies showed a similar tumor growth inhibition pattern. JDF-1 tumors were implanted s.c. in nude mice, and drugs were administered continuously by Alza minipumps (IFN-alpha 2) and in drinking water (DFMO) for 28 days. IFN-alpha 2 alone significantly inhibited JDF-1 growth, while DFMO alone had no significant inhibitory effect. The combination of IFN-alpha 2 and DFMO inhibited tumor growth in an apparent additive manner at the doses used. This was reflected in the mean tumor weights obtained at the termination of the experiment: control, 1484 +/- 187 (S.E.) mg; DFMO only, 1106 +/- 129 mg; IFN-alpha 2 only, 941 +/- 186 mg; and DFMO plus IFN-alpha 2, 620 +/- 109 mg. Assessment of mouse natural killer cell activity at the time of sacrifice showed that DFMO inhibited natural killer cell activity, while IFN-alpha 2 had no effect. DFMO was observed to inhibit ornithine decarboxylase activity in JDF-1 tumors by 78%, IFN-alpha 2 by 18%, and the combination by 78%. In addition, the drugs individually and in combination had similar inhibitory effects on JDF-1 spermidine content. One of the unexpected findings was the alteration in the spermine:spermidine ratio in the tumors treated with the combination of DFMO and IFN-alpha 2. The ratio in this group decreased to 0.44, while ratios for control, IFN-alpha 2 only, and DFMO only were 0.99, 0.66, and 0.88, respectively. These results clearly show that combined therapy with DFMO and IFN-alpha 2 is more effective than is single-drug therapy. The mechanism by which these drugs coordinately inhibit tumor growth is unclear but appears to be associated with direct inhibition of tumor cell proliferation, possibly by modulation of polyamine metabolism.

Adenocarcinoma↗

PubMed1983

Renal cell carcinoma and the clonogenic assay.

The clonogenic assay is an in vitro chemosensitivity test performed on tumor specimens and has had limited success in predicting or confirming patient response to chemotherapy. We investigated this assay system, using a 1-hour method, in 37 renal cell carcinoma specimens to determine its clinical usefulness. These specimens also were graded independently by a pathologist with respect to cell type, mitotic figures and degree of differentiation. Only 22 specimens formed at least 50 colonies per 500,000 cells plated and few specimens displayed any chemosensitivities. Marked variations of colony counts among duplicate controls or drug-treated samples demonstrated further the unreliability of the assay. Of several factors responsible for the poor performance of the assay the 2 outstanding problems were losses of clear cells in variable amounts (unique to renal cell carcinoma), and the inability to generate and maintain single cell suspensions. Pathologic correlations confirmed that predominantly clear cell carcinomas did not form colonies as well as granular cell carcinomas. Owing to these problems in its present form the clonogenic assay is not useful clinically and is unsuited particularly for renal cell carcinoma.

Adenocarcinoma↗

PubMed1983

Lack of value of radioimmunoassay for prostatic acid phosphatase as a screening test for prostatic cancer in patients with obstructive prostatic hyperplasia.

We examined the incidence of prostatic cancer in patients with an elevated radioimmunoassay for prostatic acid phosphatase and clinical benign prostatic hyperplasia on digital rectal examination. Of 295 patients screened with prostatic acid phosphatase tests 17 fulfilled the criteria of having an elevated prostatic acid phosphatase, clinically benign prostate and histological examination of the prostatectomy specimen. None of the 17 patients had histological evidence of prostatic cancer. The results confirm the predictions of mathematical models that prostatic acid phosphatase is of no practical value as a screening test for prostatic cancer in patients with clinical benign prostatic hyperplasia.

Acid Phosphatase↗

PubMed1983

Pelvic lymph node status as predictor of extracapsular tumor extension in clinical stage B prostatic cancer.

To examine the accuracy of normal pelvic lymph node status in identifying patients with clinical stage B prostatic cancer not having extracapsular tumor extension we reviewed 63 consecutive patients (39 stage B1 and 24 stage B2) treated with radical prostatectomy. Ten per cent of the patients with stage B1 lesions (tumor involving 1 lobe) and 38 per cent with stage B2 lesions (tumor involving both lobes) had extracapsular extension. Extracapsular tumor extension was more common in patients with larger, less differentiated lesions. The results suggest that a negative pelvic lymphadenectomy does not exclude with a high degree of confidence extracapsular tumor extension in patients with clinical stage B2 prostatic cancer.

Genital Neoplasms, Male↗

PubMed1983

Antibacterial activity of microbicidal cationic proteins 1 and 2, natural peptide antibiotics of rabbit lung macrophages.

Microbicidal cationic proteins 1 and 2, peptides derived from rabbit lung macrophages, were tested for bactericidal activity against various bacterial species. Both were highly active against diverse gram-positive and gram-negative organisms under conditions of near-neutral pH (between 7 and 8) and relatively low ionic strength. Susceptible species included Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Listeria monocytogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae, Haemophilus influenzae, Escherichia coli, and Serratia marcescens. Streptococcus agalactiae, type 1A, was less susceptible than the aforementioned organisms or S. agalactiae, type 3. Bordetella bronchiseptica, a common commensal and pathogen of the rabbit respiratory tract, was completely resistant to both peptides.

Animals↗

PubMed1983

Successful treatment of spinal arachnoiditis due to coccidioidomycosis. Case report.

An unusual case is reported of a patient with spastic paraparesis who was found to have severe spinal arachnoiditis due to Coccidioides immitis. Despite an obstructive hydrocephalus and a spinal subarachnoid block, the patient was treated effectively with surgery (shunting) and antifungal therapy (amphotericin and ketoconazole). He remains asymptomatic 3 years after diagnosis. Aggressive surgical and medical treatment of coccidioidal infection of the central nervous system can be beneficial, even in patients with the worst prognosis.

Adult↗

PubMed1981

Embryonal rhabdomyosarcoma of the genitourinary organs.

We report on 14 patients with embryonal rhabdomyosarcoma of the genitourinary organs treated with combined modality therapy. Six patients with paratesticular lesions are free of tumor 7 to 72 months (mean 44) after diagnosis, while 6 of 8 with pelvic lesions are free of tumor 18 to 132 months (mean 61) following diagnosis. Two patients died of metastases. Over-all, 2-year survival free of relapse was obtained in 9 of 11 patients (81 per cent). Of 4 patients with pelvic lesions who were treated with primary radiation-chemotherapy without exenteration 3 were managed successfully but 1 required urinary diversion for vesical fibrosis. Current concepts in the management of embryonal rhabdomyosarcoma are discussed.

Adolescent↗

PubMed1981

Increased content of microbicidal cationic peptides in rabbit alveolar macrophages elicited by complete Freund adjuvant.

We measured the microbicidal peptides MCP-1 and MCP-2 in rabbit alveolar macrophages (AM), comparing rabbits pretreated with complete Freund adjuvant with untreated control animals. Levels of MCP-1 increased from 4.7 +/- 0.6 microgram/10(7) resident AM to 13.2 +/- 0.1 microgram/10(7) complete Freund adjuvant-elicited AM. MCP-2 levels rose from 1.8 +/- 0.1 microgram/10(7) resident AM to 7.3 +/- 0.4 microgram/10(7) complete Freund adjuvant-elicited AM. The activities of five lysosomal hydrolases (beta-D-glucuronidase, beta-D-galactosidase, acid phosphatase, N-acetyl-beta-D-galactosaminidase, and N-acetyl-beta-D-glucosaminidase) were 44 to 96% higher in complete Freund adjuvant-elicited AM, and lysozyme activity was three- to fourfold higher. As MCP-1 and MCP-2 are major constituents of rabbit AM and exhibit potent antibacterial and antifungal properties, they may contribute to the expression of microbicidal activity in both resident and activated states.

Animals↗

PubMed1980