Rho GTPase activating protein 21-mediated regulation of prostate cancer associated 3 gene in prostate cancer cell.

The overexpression of the prostate cancer antigen 3 (PCA3) gene is well-defined as a marker for prostate cancer (PCa) diagnosis. Although widely used in clinical research, PCA3 molecular mechanisms remain unknown. Herein we used phage display technology to identify putative molecules that bind to the promoter region of PCA3 gene and regulate its expression. The most frequent peptide PCA3p1 (80%) was similar to the Rho GTPase activating protein 21 (ARHGAP21) and its binding affinity was confirmed using Phage Bead ELISA. We showed that ARHGAP21 silencing in LNCaP prostate cancer cells decreased PCA3 and androgen receptor (AR) transcriptional levels and increased prune homolog 2 (PRUNE2) coding gene expression, indicating effective involvement of ARHGAP21 in androgen-dependent tumor pathway. Chromatin immunoprecipitation assay confirmed the interaction between PCA3 promoter region and ARHGAP21. This is the first study that described the role of ARHGAP21 in regulating the PCA3 gene under the androgenic pathway, standing out as a new mechanism of gene regulatory control during prostatic oncogenesis.

[Epidemiology of chronic kidney disease in a population: residents in the territory of Umbria "Gubbio - Gualdese"]. / Epidemiologia della malattia renale cronica in una popolazione: i residenti nel territorio umbro "eugubino-gualdese"

The incidence of chronic kidney disease (CKD) has clearly increased in recent years. It is likely to be correlated with the aging population and with the growing association with vascular diseases. In Italy, there are different registers of dialysis and transplantation, providing an excellent means of monitoring patients in substitution treatment. On the contrary, few material is in our possession regarding CKD patients on conservative therapy. Therefore it lacks a necessary mean to implement mechanisms of prevention and programming for a disease that increasingly shows significant social - health consequences.

Electroweak S and T parameters from a fixed point condition.

We consider the standard model without the Higgs boson, where the Goldstone modes are described by a nonlinear sigma model. We study the renormalization group flow of the sigma model coupling f and of the electroweak parameters S and T. The condition that the couplings reach a fixed point at high energy leaves the low energy values of f and T arbitrary (to be determined experimentally) and fixes S to a value compatible with electroweak precision data.

Isolation and characterization of unusual Mycoplasma spp. from captive Eurasian Griffon (Gyps fulvus) in Sicily.

Mycoplasmas have been isolated from birds of prey during clinical examinations, but their significance to the health of raptors is unclear. We report the isolation and characterization of four mycoplasmas found in the upper respiratory tract of four sick Eurasian Griffon (Gyps fulvus) that were housed in a Sicilian rehabilitation center at Ficuzza, near Palermo in Sicily, before reintroduction into the wild. These included Mycoplasma gallinarum, an unidentified mycoplasma highly similar to Mycoplasma glycophilum, and two unidentified mycoplasmas with similarities to Mycoplasma falconis and Mycoplasma gateae.

Effect of two-hour daily hemodialysis and sham dialysis on breath isoprene exhalation.

BACKGROUND: Isoprene, a volatile hydrocarbon produced by the human organism, is currently being extensively investigated because the mechanisms underlying its endogenous origin are unknown and because experiments suggest it is toxic and cancerogenous. Previous reports of increases in breath isoprene concentrations during 4-hour, thrice-weekly hemodialysis, but not during continuous ambulatorial peritoneal dialysis, prompted us to assess the behavior of isoprene in another dialytic modality, i.e., short daily hemodialysis (short DHD). Furthermore, in order to determine whether removal of solutes and/or contact of blood with the dialytic membrane influenced the metabolism of isoprene, we performed a sham short hemodialysis session in a subgroup of 8 patients (sham short HD), i.e., with blood flowing through a dialyzer but without dialysate and ultrafiltration. METHODS: The present study evaluates the effects of a two-hour short DHD and a two-hour session of sham HD on isoprene breath levels, as determined by gas chromatography before, during and after sessions. Parallel analyses of ambient air and monitoring of blood pressure and heart rate were performed. RESULTS: Both short DHD and sham DHD induced an increase in breath isoprene exhalation in all patients without being associated with significant hemodynamic variations. CONCLUSION: These findings suggest that the increase in breath isoprene after a session of hemodialysis is neither a reaction to mevalonate depletion nor to metabolic variations induced by the depurative effect, because these changes do not occur during sham HD. It is not related to hemodynamic changes because none were observed in this experimental model. The isoprene increase seems to be of metabolic origin and appears to be connected in some way with the extracorporeal circuit. These interesting findings provide a further impulse to study the biosynthetic pathways involved and to investigate the medical and biological significance of isoprene in humans.

[Historical Archives of Italian Nephrology. Diabetic nephropathy and insulin discovery: two parallel histories]. / Archivi storici della Nefrologia Italiana. Nefropatia diabetica e scoperta dell'insulina: due storie parallele.

In 1936, Kimmelstiel and Wilson described the nodular glomerulosclerosis in patients with diabetes mellitus on insulin treatment. The nodular glomerulosclerosis is referred to as diabetic nephropathy. Fifteen years earlier insulin was discovered. This discovery at the University of Toronto (Canada) in 1921-22 by Banting, Macleod, Best and Collip was one of the most dramatic events in the history of the treatment of the disease. The impact of insulin was so sensational because of the incredible effect it had on diabetic patients. Those who first watched starved, sometimes comatose, diabetics receive insulin and return to life witnessed one of the genuine miracles of modern medicine. The discovery has became the "elixir of life" for millions of human beings around the world. Insulin had not emerged out of a vacuum but was the culmination of years of work by dozens of scientists in many countries. The Canadian scientists were the first to succeed in isolating insulin. Their work, however, was accurately constructed to confirm the ideas of earlier researchers, such as Murray, Paulesco, Allen, Minkowski, Derwitt, Zuelzer. These men, in addition to Banting, Macleod, Best and Collip, knew they were making medical history but paradoxically, with their "elixir of life" they allowed some complications of diabetes to emerge. Diabetic nephropathy was one of them. The struggle of the "Toronto quartet" for credit was inspired by man's desire to have a place in history, to have a sort of immortality open to him, an aspiration that is certainly legitimate. But perhaps the Canadian group misjudged both their situation and posterity's point of view. They probably failed to consider the unintentional effect of insulin treatment: diabetic nephropathy as a consequence of adding years to a diabetic's life.

Comparison between oscillometric and auscultatory methods of ambulatory blood pressure measurement in hemodialysis patients.

INTRODUCTION: 24-hour ambulatory blood pressure monitoring (ABPM) is commonly used in clinical and research practice. Different methods have been used in BP recording, cuff-oscillometric or Korotkoff sound, and validation studies during ABPM have been performed on general as well as hypertensive populations. Hemodialysis (HD) patients have a high percentage of complications, such as vascular diseases, and they are subject to hyperkinetic blood flows and abrupt body weight changes secondary to HD, which can invalidate BP recording. Therefore, we wanted to compare the 2 methods on an HD population. PATIENTS AND METHODS: We performed 86 ABPMs on 44 patients (aged 60.8 +/- 17.2 years) by using a device capable of the simultaneous recording of oscillometric and auscultatory BP (A&D Takeda TM2421). The data obtained with the 2 different ABPM methods have been compared, and the differences between auscultatory and oscillometric determinations have been analyzed, as presented by Bland and Altman [1986]. RESULTS: The percentage of valid recordings was significantly higher with the oscillometric method than with the auscultatory method (93.6 +/- 11.3% vs. 71.7 +/- 17.04%, p < 0.001). 24-hour diastolic BP and night-time systolic BP were higher when recorded with the oscillometric method (DBP = 75.4 +/- 9.6 mmHg vs. 71.8 +/- 9.6 mmHg, p < 0.001, asleep SBP = 119.7+/-23.3 mmHg vs. 116.2 +/- 25.0 mmHg, p < 0.001), and the systolic night/day BP ratio was also higher(0.92 +/- 0.10vs.0.90 +/- 0.10, p < 0.001). Finally, the BP coefficient of variation ((SD/mean BP) x 100) was higher when auscultatory determinations were used (16.1 +/- 4.6 vs. 14.6 +/- 4.9). The limits of agreement between auscultatory and oscillometric BP determinations were for SBP = -6.44; 7.84 and for DBP = -3.66; 10.86. CONCLUSIONS: Differences between 24-hour oscillometric and auscultatory ABPM were reported in HD patients: the diastolic 24-hour and asleep systolic BP values and the systolic night/day ratio obtained with the oscillometric method were significantly higher. The higher coefficient of variation reported with the auscultatory method and the wider limits of agreement suggest that the 2 methods do not fully coincide and, in our opinion, the oscillometric method is preferable, due to the higher number of 24-hour valid measurements.

Vertebral bone mineral density changes in female rheumatoid arthritis patients treated with low-dose methotrexate.

OBJECTIVE: To assess vertebral bone mineral density (BMD) changes in rheumatoid arthritis (RA) patients taking low-dose methotrexate (MTX). METHODS: We evaluated in a 2-year, longitudinal study female RA patients, who had recently started a disease-modifying antirheumatic drug (DMARD), divided into two groups: group A, receiving MTX, and group B, receiving other DMARDs. Lumbar spine BMD was assessed at baseline and every year; RA activity was assessed every 3 months. RESULTS: Sixty-two patients were enrolled in the study; 40 completed the follow-up period: 22 of group A, and 18 of group B. The results after 2 years showed that both groups lost bone significantly vs baseline (p < 0.001) in a comparable fashion: group A (mean +/- SD) -3.9 +/- 4.9% vs group B -3.0 +/- 3.7% (p = NS). The patients who showed active disease lost significantly (p < 0.05) more bone (-5.5 +/- 3.8%) than those with less active disease (-1.1 +/- 3.6%), independently of their DMARD. CONCLUSION: Low-dose MTX in RA does not seem to exert relevant effects on trabecular bone.

A prospective study on mother-to-infant transmission of hepatitis C virus.

To assess the rate of mother-to-infant transmission of hepatitis C virus (HCV) and to identify potential risk factors for transmission, we followed up (mean 22.4 months, range 1-7.5 years) a cohort of 291 babies born to anti-HCV-positive mothers, 40 of whom were also HIV coinfected. Seventeen (5.8%) babies acquired HCV infection, but none became icteric. All babies developed chronic HCV infection with 16 babies showing elevated levels of ALT. The rate of transmission was higher in babies born to mothers coinfected with HIV than in those born to mothers with HCV alone (22.5 vs. 3.2%, p < 0.0001). No association was seen between a specific maternal HCV genotype and an increased risk of neonatal infection. The median level of HCV-RNA was higher in mothers who transmitted infection than in those who did not, although the ranges overlapped. In this study, maternal history of chronic liver disease, mode of delivery and type of feeding were not predictive of HCV infection.

Morbidity and mortality due to liver disease in children undergoing allogeneic bone marrow transplantation: a 10-year prospective study.

We have conducted a long-term prospective study of children undergoing bone marrow transplantation (BMT) to assess morbidity and mortality for liver disease. One hundred eleven consecutive children were enrolled between June 1985 and June 1995 and were followed-up for a median of 5.5 years after BMT. Before transplant 48/111 children (43%) had abnormal alanine aminotransferase (ALT), none were HBsAg+ and 4/111 were anti-HCV+. After BMT 4/111 patients (3. 6%) died of liver failure. No relationship was found between pretransplant hepatitis B (HBV) or C (HCV) infection or elevated transaminases and development of severe liver damage. Eighty-two out of one hundred and eleven patients (74%) had abnormalities of ALT after BMT, transient (n = 54) or persistent (n = 28). None developed clinical signs or symptoms of end stage liver disease or of cirrhosis during follow-up. No significant difference in prevalence of liver disease, was found between children with normal or abnormal ALT at BMT (relative risk [RR] = 1.04). HCV infection could be implicated in the etiology of chronic liver disease in 14/28 patients; 2 other patients were found infected by HBV alone (1 case) or combined with HCV (1 case). In the remaining 12 the etiology of chronic liver disease could not be defined. Posttransplant hepatitis B occurred in 4/111 children (3.6%), including a recipient from a donor who had been previously vaccinated against HBV, while no patient who had been vaccinated developed hepatitis B. The rate of posttransplant seroconversion to anti-HCV was 15%.

G-CSF stimulated donor granulocyte collections for prophylaxis and therapy of neutropenic sepsis.

BACKGROUND: The administration of granulocyte colony-stimulating factor (G-CSF) increases the granulocyte count in normal donors and enables the collection of large numbers of mature myeloid cells by leukapheresis. This has potential value in the treatment of sepsis unresponsive to antibiotics in patients with severe neutropenia. AIM: To evaluate the tolerability of granulocyte collections in normal donors receiving G-CSF, the optimal method of collection and the clinical factors influencing the efficacy of granulocyte infusions. METHODS: Analysis of the outcome of 55 granulocyte collections from 26 donors for progressive bacterial or fungal sepsis in neutropenic patients (n = 8) or as prophylaxis in patients with recent fungal infections undergoing allogeneic bone marrow transplantation (BMT) (n = 3). RESULTS: G-CSF was well tolerated in most donors. Fatigue occurred commonly after the second collection. The median WCC per 200-220 mL bag was 351 x 10(9)/L. Collections were optimised with the use of a sedimenting agent (dextran) and a deepened interface setting on the cell separator. There was only a weak correlation between the number of granulocytes infused and the increment in the patient, but levels were usually maintained > or = 0.5 x 10(9)/L for the next 24 hours. The infusions were successful in three septic patients without multi-organ dysfunction and prophylactically, in two patients with localised fungal infections undergoing MBT. The infusions were not beneficial in patients with septicaemia and established organ dysfunction or with extensive pulmonary aspergillosis. CONCLUSIONS: G-CSF mobilised granulocyte collections are feasible and the preliminary evidence suggests that the infusion of these cells may be useful early in the prophylaxis or treatment of severe neutropenic sepsis.

Health care for the uninsured in Duluth.

Providing health care for Minnesota's uninsured population continues to be both a clinical and political challenge. Between October 1, 1991, and September 30, 1993, 1,260 previously uninsured people received charity health care in Duluth. No one was excluded because of pre-existing conditions. Their utilization of services and associated costs can help project the health care needs and costs of care for uninsured Minnesotans. This group of uninsured people used a different mix of health care services compared with insured Minnesotans, and their total costs (including prescriptions) were about 15% greater. A large proportion of these uninsured Minnesotans had chronic health conditions and a "pent-up need" for services and medications. This experience demonstrated that it is possible to administer a limited benefits plan in coordination with existing public and private resources.

Automated analysis of urinary catecholamines by high-performance liquid chromatography and on-line sample pretreatment.

A simple and automated solid-phase extraction for the selective and quantitative HPLC analysis of free catecholamines in urine is described. The urinary catecholamines react with diphenylboric acid, giving a complex at pH 8.5 which is strongly retained on a PLRP-S cartridge; elution is accomplished with the same mobile phase used for HPLC analysis. Separation is performed by ion-pair reversed-phase HPLC, with sodium heptanesulphate as counter-ion, and a totally end-capped C18 analytical column. Quantitation is achieved with an electrochemical detector. A Spark Holland Prospekt system controls the on-line solid-phase extraction, preconcentration and direct elution to the LC column. Chromatography run-time is 10 min and the total time to process one urine sample is ca. 12 min.

Mother-to-infant transmission of hepatitis C virus. Lombardy Study Group on Vertical HCV Transmission.

To assess the risk of mother-to-infant transmission of hepatitis C virus (HCV), we followed up 116 babies of anti-HCV positive mothers, of whom 22 were coinfected with HIV and 94 had HCV alone. None of the babies whose mothers had HCV alone acquired HCV, while 8 babies (36%; p < 0.001) of mothers co-infected with HIV acquired HCV (5 babies) or HCV and HIV (3). There was no association between any specific maternal HCV genotype and enhanced risk of neonatal infection. HCV-RNA levels were significantly higher (p < 0.05) in mothers with HIV coinfection than in those with HCV alone. These data indicate that maternal HIV status correlates with enhanced level of viraemia which favours neonatal infection.

[The hadron therapy project]. / Ii progetto adroterapia.

The neologism "hadrontherapy" means radiotherapy with hadrons, which are the particles constituted by quarks, such as protons, neutrons and ions. The theoretical considerations about the clinical advantages this treatment modality can yield and the results obtained at the centers where it has already been used justify the proposal to project a center of this kind also in our Country. To this purpose, two of the authors of this paper (U. Amaldi, G. Tosi) founded the TERA Group formed by physicists, engineers and radiotherapists who work in close collaboration on a feasibility study for a hadrontherapy facility. The first aim of the Hadrontherapy Project is to design a center equipped with a synchrotron which, at the beginning, will accelerate negative hydrogen ions (H-) which will first produce 70-250 MeV proton beams and, then accelerate light ions (up to 16O) to 430 MeV/amu. This accelerator will serve four or five treatment rooms where patients can be irradiated simultaneously. Two rooms will be equipped with a fixed horizontal beam for the treatment of eye, head and neck tumors; the others will be equipped with rotating gantries to administer, in any clinical situation, really adequate treatment. Such a unit, when enough experience is fained, will allow at least 1000 patients to be treated yearly. The synchrotron injector will be designed so as to allow, parallel to the radiotherapy activities, other applications of medical and biological interest such as: the production of radioisotopes for diagnostic use (especially positron emitters), the analysis of trace elements through the PIXE technique and the production of thermal and epithermal neutrons for boron neutron capture therapy.

[Radiographic examination of the pelvis in patients under periodic hemodialysis for terminal uremia]. / L'esame radiografico del bacino nel paziente sottoposto ad emodialisi periodica per uremia terminale.

Significant signs of uremic osteodystrophy were found at Rx examination of the pelvis in 29 out of 72 uremic patients (40%) undergoing maintenance hemodialysis. It is therefore thought that Rx of the pelvis, although it is more significant for some signs (brown tumors, alterations of the trabecular structure, enlargement of Ward's triangle) than for others, such as subperiosteal resorption, should not be neglected in these patients.

[The parenteral administration of essential amino acids in patients on periodic hemodialysis treatment. A pilot study]. / Somministrazione parenterale di aminoacidi essenziali (AAE) nei pazienti in trattamento emodialitico periodico. Studio pilota.

In an attempt to improve the nutritional status of seven hemodialysed patients, 500 ml of a 5.5% nephrological essential amino acid solution (EAA) were administered during each dialysis session for 2 months. At the end of this treatment, a significant increase in albuminemia was found (p < 0.05). These results are an encouragement to continue this therapy, especially if it is kept in mind that the half-life of albumin is much shorter than the period of EAA administration.

[Surveillance by skeletal radiography of patients under hemodialysis. Radiographic examination of the vertebral column]. / La sorveglianza radiologica scheletrica nei pazienti emodializzati. L'esame radiografico della colonna vertebrale.

The authors describe damage to the spine observed by x-ray in patients on maintenance hemodialysis. They stress the importance of including x-ray examination of the spine among the routine checks performed in these patients.