Phosphorylation of the androgen receptor by PIM1 in hormone refractory prostate cancer.

Integration of cellular signaling pathways with androgen receptor (AR) signaling can be achieved through phosphorylation of AR by cellular kinases. However, the kinases responsible for phosphorylating the AR at numerous sites and the functional consequences of AR phosphorylation are only partially understood. Bioinformatic analysis revealed AR serine 213 (S213) as a putative substrate for PIM1, a kinase overexpressed in prostate cancer. Therefore, phosphorylation of AR serine 213 by PIM1 was examined using a phosphorylation site-specific antibody. Wild-type PIM1, but not catalytically inactive PIM1, specifically phosphorylated AR but not an AR serine-to-alanine mutant (S213A). In vitro kinase assays confirmed that PIM1 can phosphorylate AR S213 in a ligand-independent manner and cell type-specific phosphorylation was observed in prostate cancer cell lines. Upon PIM1 overexpression, AR phosphorylation was observed in the absence of hormone and was further increased in the presence of hormone in LNCaP, LNCaP-abl and VCaP cells. Moreover, phosphorylation of AR was reduced in the presence of PIM kinase inhibitors. An examination of AR-mediated transcription showed that reporter gene activity was reduced in the presence of PIM1 and wild-type AR, but not S213A mutant AR. Androgen-mediated transcription of endogenous PSA, Nkx3.1 and IGFBP5 was also decreased in the presence of PIM1, whereas IL6, cyclin A1 and caveolin 2 were increased. Immunohistochemical analysis of prostate cancer tissue microarrays showed significant P-AR S213 expression that was associated with hormone refractory prostate cancers, likely identifying cells with catalytically active PIM1. In addition, prostate cancers expressing a high level of P-AR S213 were twice as likely to be from biochemically recurrent cancers. Thus, AR phosphorylation by PIM1 at S213 impacts gene transcription and is highly prevalent in aggressive prostate cancer.

Effects on apoptosis and reactive oxygen species formation by Jurkat cells exposed to 50 Hz electromagnetic fields.

The effect of exposure to 50 Hz electromagnetic field on a human T-leukaemia cell line (Jurkat) was investigated by evaluating the reactive oxygen species (ROS) production and apoptosis, both spontaneous and induced by a specific anti Fas/CD95 monoclonal antibody (anti-Fas). Our results suggest that 1 h intermittent (5 min field on/10 min field off) exposure does not affect ROS formation, while a slight but statistically significant decrease of both spontaneous and anti-Fas-induced apoptosis was observed.

Health care costs of therapy-refractory schizophrenic patients treated with clozapine: a study in a community psychiatric service in Italy.

This study evaluates the utilization of clozapine in the treatment of therapy-refractory schizophrenia in terms both of patterns of care and of health care costs in a community psychiatric service in Italy. Data covering the year prior to commencing clozapine and the year following the initiation of the therapy were collected. Clinical outcome was assessed by means of the Clinical Global Impression (CGI) and Global Assessment of Functioning (GAF) scales. Cost analysis followed a two-step procedure: (i) to record all health care services provided to patients and (ii) to assign a monetary value to each service. Three of the 15 patients enrolled in the study dropped out before the end of the 12-month period of therapy. Considering the 12 patients on clozapine treatment for at least 1 year, clinical improvements are associated with a substantial modification of the pattern of care. While patients in the pre-clozapine period were mainly managed in hospital settings, patients on clozapine were prevalently placed in the community and participated in intensive rehabilitative programmes. The higher costs of drug therapy and community services in the post-clozapine period were more than offset by the lower costs of acute hospital care.

[Epidemiology of male infertility]. / Epidemiologia dell'infertilità maschile.

OBJECTIVE: The aim of the present study has been to analyze the variation of the main parameters which define sperm quality in a group of men who were referred to our center of sterility during the last ten years of activity. MATERIAL AND METHODS: Over the last ten years, we have examined 3203 men ranging from 25 to 50 years of age. We have considered different parameters of evaluation, such as semen volume, motility, total motility count and morphology of spermatozoa; the same parameters have been considered for a group of 192 men accustomed to consuming coffee, alcohol and tobacco. RESULTS: We have observed no significative variations with respect to sperm volume; in spite of this result, we have registered a considerable reduction of the frequency of men with normal sperm quality, when we have considered parameter such as sperm motility. The evaluation of the total motility count has confirmed a progressive reduction during the considered period of time. This parameter has also shown the existence of a circannual rhythm for the production of spermatozoa, which results minimum during the winter and during the warmest months, while it improves during spring and autumn. During the considered period, the study of morphology has shown a progressive reduction of men with normal semen quality. CONCLUSION: The results of our epidemiologic study, conducted over a group of men who have been referred to our center of sterility during the last ten years, confirm that the group representative of Northern Italy has faced a decline of sperm quality.

[Request for psychiatric admission: data from eight general hospital psychiatric wards in Lombardy]. / Sulla richiesta di ricovero psichiatrico: i dati di otto SPDC in Lombardia.

OBJECTIVE: To describe requests of admissions to eight General Hospital Psychiatric Wards (SPDC) in Lombardy, Italy, during November 1995. DESIGN: Descriptive prospective multicenter study. SETTING: SPDCs of Busto Arsizio (VA), Calcinate (BG), Desio (MI), Magenta (MI), Merate (LC), Milano San Paolo I, Pavia, Treviglio (BG). The global catchment area sums up to 11% of the whole regional area, and to 18% of the population. MAIN OUTCOME MEASURES: We used a previously developed flow chart with two major key points: who decided to go to the hospital? Did a doctor confirm this initiative? Main sociodemographic characteristics, ICD10 diagnosis and previous psychiatric admissions were collected for each admission. RESULTS: Admissions were 315, patients 246. In 9.5% of cases patients asked for admission without any medical advice. In one third of cases the ward psychiatrist was the first doctor to visit the patient. Compulsive admissions (TSO) were 45 (14.3%), although patient's initiative lacked in 55.6% of cases. A referral from Outpatient Departments (CPS) was present in 28.2%. First-ever admitted were 63 (25.6%): 20.7% sent by CPS, 16% by GPs, 11% by other non psychiatric wards. CONCLUSIONS: Although Goldberg & Huxley's model described General Hospital Psychiatric Wards as the last level of intervention, our data show that Italian SPDCs work as "front lines" services: less than one admission out of two were referred by a psychiatrist. Problems raised by "self-referred" patients are conspicuous and an evaluation of the filtering function of CPSs seems necessary. In this regard, a comparison with different modalities of Department organization could be useful.

Expanded polytetrafluoroethylene surgical membrane in ovarian surgery on the rabbit. Biocompatibility, adhesion prevention properties and ability to preserve reproductive capacity.

OBJECTIVE: To evaluate the biocompatibility, adhesion prevention properties and ability to preserve reproductive capacity of polytetrafluoroethylene surgical membrane in ovarian surgery on the rabbit. STUDY DESIGN: In two groups of female rabbits a standard lesion was made on each ovary. In group 1, one ovary was partially covered with a flat sheet of the surgical membrane, and the other was left uncovered so that each rabbit served as its own control. In group 2, one ovary was again left uncovered to serve as an internal control, and the other was completely covered with a "cap" of the surgical membrane. Laparotomies were performed several weeks postoperatively after the rabbits were mated with fertile males; adhesions were evaluated, and the number of cornual pregnancies was determined. RESULTS: In group 1, 67.9% of the control ovaries and 7.1% of the partially covered ovaries had adhesions (P < .001); in the uterine horn on the control side, 32.1% of the rabbits exhibited cornual pregnancies (1.14 +/- 1.72 [mean +/- SD] pregnancies per rabbit), whereas on the experimental side, 89.3% of the rabbits exhibited cornual pregnancies (3.89 +/- 1.58 per rabbit). In group 2, 83.3% of the control ovaries and 11.1% of the covered ovaries had adhesions (P < .001); in the uterine horn on the control side, 23.5% of the rabbits exhibited cornual pregnancies (2 +/- 1.1 per rabbit), whereas on the experimental side, 100% of the rabbits exhibited cornual pregnancies (4.8 +/- 0.9 per rabbit). CONCLUSION: The surgical membrane is an excellent device for preventing the formation of adhesions to the ovary after surgery in rabbits, preserving the reproductive capacity of the ovary.