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Understanding cell proliferation regulation in hormone refractory prostate cancer may provide answers for novel solutions. Protein tyrosine phosphatases have been thought to have key roles in regulating cell proliferation and be involved in oncogenesis, although to our knowledge their functional roles in human prostate cancer remain unknown. Human prostatic acid phosphatase (PAcP), a major phosphatase in prostate epithelium, has been shown to function as a neutral protein tyrosine phosphatase in these cells. We evaluated the biological significance of cellular prostatic acid phosphatase expression in human prostate cancer cells.Immunohistochemical testing of human prostate cancer archival specimens was done to evaluate the expression of cellular PAcP. Immunoprecipitation and immunoblotting were performed to determine cellular PAcP and SH2 domain-bearing tyrosine phosphatase-1 levels as well as tyrosine phosphorylation of c-ErbB-2/neu in different human prostate cancer cells. The biological behavior of LNCaP derivative sublines was characterized in vitro and in vivo by soft agar analysis and xenograft animal inoculation.Immunohistochemical staining of human prostate clearly showed that cellular levels of PAcP significantly decreases in prostate cancer cells (p0.001). The results of biochemical characterization revealed that the cellular level of PAcP but not SHP-1, another differentiation associated protein tyrosine phosphatase, consistently correlated negatively with the growth of several human prostate cancer cell lines. Reintroducing cellular PAcP activity in prostate cancer cells by PAcP complementary DNA transfection resulted in decreased tyrosine phosphorylation of c-ErbB-2/neu, decreased proliferation rates in culture as well as decreased anchorage independent growth in soft agar. The xenograft animal model demonstrated that a higher tumor growth rate as well as larger size is associated with a lower level of cellular PAcP.Cellular PAcP can down-regulate prostate cancer cell growth, at least partially by dephosphorylating c-ErbB-2/neu. Therefore, decreased cellular PAcP expression in cancer cells may be involved in prostate cancer progression.

To determine the effect of zidovudine (ZDV) on the pharmacokinetic disposition of recombinant soluble CD4 immunoglobulin G (rCD4-IgG) and to evaluate the safety and preliminary activity of concurrent administration of ZDV with rCD4-IgG, we undertook an open-label, dose-escalating, 12-week study. The regimens of intravenous rCD4-IgG and oral ZDV we used were (a) 300 micrograms/kg rCD4-IgG twice per week and 300 mg ZDV per day, (b) 300 micrograms/kg rCD4-IgG twice per week and 600 mg ZDV per day, (c) 1,000 micrograms/kg rCD4-IgG twice per week and 300 mg ZDV per day, (d) 1,000 micrograms/kg rCD4-IgG twice per week and 600 mg ZDV per day, and (e) 3,000 micrograms/kg rCD4-IgG twice per week and 300 mg ZDV per day. Subjects were recruited from three AIDS clinical trials units. Forty-one patients with HIV infection who had CD4 cell countsor = 500 cells/mm3 and120 days of previous ZDV therapy participated. Pharmacokinetic interactions were assessed with the second regimen. Mean calculated peak serum rCD4-IgG concentrations were 5.47 micrograms/ml with ZDV and 8.28 micrograms/ml without ZDV, with serum half-lives of 34.2 and 32.0 h, respectively. Antibodies to rCD4-IgG were not detected. Seven episodes of severe adverse events occurred in five patients: one episode each of severe nausea, fever, or abnormal liver function tests and four episodes of severe neutropenia. Mean hemoglobin and neutrophil counts decreased, and mean platelet counts increased in all regimens, but there were no significant differences among regimens, rCD4-IgG dose, or ZDV dose.(ABSTRACT TRUNCATED AT 250 WORDS)

When polymorphonucleocytes are incubated in proteinaceous fluid, they cause extensive protein degradation, which leads to accumulation of free amino acids. The authors tested whether these free amino acids, particularly valine and leucine, also accumulate in human abscess fluids, but not in other body fluids, and thus could be a specific and distinguishing marker for the presence of an abscess.Thirty fluids, obtained by percutaneous drainage from 28 patients, were lyophilized and reconstituted in 2H2O before in vitro 1H magnetic resonance (MR) spectroscopy. Concentrations of valine and leucine were determined by comparison of spectra before and after addition of known amounts of valine and leucine. Two chart reviewers, blinded to the spectroscopic results, categorized cases as abscess (n = 14), non-abscess (n = 15), or infection but not abscess (n = 1).The concentration of valine and leucine was significantly higher in the abscess fluids, 2.57 +/- 1.90 mM than in the non-abscess fluids, 0.25 +/- 0.33 mM (P.001). The one infected fluid which was not an abscess had no amino acids. Using 0.8 mM as the threshold concentration of valine and leucine necessary for the diagnosis of abscess resulted in a sensitivity rate of 86% and a specificity rate of 94%.The authors conclude that identification of high concentrations of valine and leucine by 1H MR spectroscopy may be a specific test for the diagnosis of abscess. This technique merits further investigation in vivo.

To determine the quantitative microbiologic response and the clinical response of patients with Mycobacterium avium complex bacteremia and AIDS to an oral antimycobacterial regimen.A phase II, multicenter clinical trial.Four university-affiliated medical centers.Forty-one patients with HIV infection who had at least two consecutive blood cultures positive for M. avium complex and who had not received previous antimycobacterial therapy were enrolled in the study. Thirty-one patients were evaluable with regard to the efficacy of the oral regimen.Patients received a combination of orally administered rifampin (600 mg), ethambutol (15 mg/kg body weight), clofazimine (100 mg once daily), and ciprofloxacin (750 mg twice daily) for 12 weeks. Parenterally administered amikacin, 7.5 mg/kg daily for 4 weeks after the first 4 weeks of oral therapy, was used at the discretion of the individual investigator.Clinical symptoms, Karnofsky scores, and adverse events were monitored. Colony counts for M. avium complex were determined.The mean logarithmic (log) baseline colony count decreased from 2.1 to 0.7 after 4 weeks of oral therapy (P less than 0.001). Suppression of bacteremia was sustained throughout therapy. Thirteen patients (42%) became culture negative during therapy. The mean duration of treatment was 9.7 weeks. Nineteen evaluable patients (61%) completed 12 weeks of therapy. Adverse reactions to one or more agents were common.A rapid reduction in symptoms and bacteremia can be achieved as early as week 2 of therapy using an oral regimen of rifampin, ethambutol, clofazimine, and ciprofloxacin. Colony counts rose dramatically after therapy was discontinued, suggesting that more prolonged periods of therapy are necessary to eradicate systemic infection.