Phenotypes and genotypes of erythromycin-resistant pneumococci in Italy.

Of 120 erythromycin-resistant pneumococci isolated in Italian hospitals, 39 (32.5%) were M-type isolates, carrying the mef gene alone. The mef gene was also detected, together with erm(AM), in one constitutively resistant isolate and in five isolates of the partially inducible phenotype.

Gene expression profile of Vitamin D3 treated HL60 cells shows an incomplete molecular phenotypic conversion to monocytes.

By high density oligonucleotide microarrays we have studied the expression profile of proliferating and VD treated HL60 cells and the molecular phenotype of VD monocytes and that of CD14+ peripheral monocytes has been compared. The results indicate that important changes in functional categories of the differentially expressed genes underlie the differentiation transition from myeloblasts to monocytes. This differential gene expression pattern leads to an increased expression of mRNAs involved in surface and external activities since many of the VD induced genes belong to ligand binding, receptors, cell surface antigens, defense/immunity and adhesion molecules functional categories.

Physiological levels of 1alpha, 25 dihydroxyvitamin D3 induce the monocytic commitment of CD34+ hematopoietic progenitors.

Although supraphysiological levels of 1alpha, 25 dihydroxyvitamin D3 (VD) have been demonstrated extensively to induce the monomacrophagic differentiation of leukemic myelo- and monoblasts, little is known about the role that physiological levels of this vitamin could play in the regulation of normal hematopoiesis. To clarify this issue, we adopted a liquid-culture model in which cord blood CD34+ hematopoietic progenitors, induced to differentiate in the presence of different combinations of cytokines, were exposed to VD at various concentrations and stimulation modalities. The data obtained show that physiological levels of VD promote a differentiation of CD34+ hematopoietic progenitors characterized by the induction of all the monomacrophagic immunophenotypic and morphological markers.

Oxidative DNA damage as a marker of aging in WI-38 human fibroblasts.

Cause-effect relationships between oxidative stress, DNA damage and aging were investigated in WI-38 human diploid fibroblasts at 21, 41 or 58 population doublings (PDs), corresponding to young, middle age or old fibroblasts, respectively. Oxidative DNA damage was evaluated by immunohistochemical detection of 8-hydroxy-2'deoxyguanosine (8-OHdG) adducts or by single cell microgel electrophoresis (COMET assay). Aging was evaluated by growth rate, senescence-associated-beta-galactosidase (SA-beta galactosidase) activity, cell cycle distribution, and expression of p21.

In vitro antibacterial activities of AF 3013, the active metabolite of prulifloxacin, against nosocomial and community Italian isolates.

AF 3013, the active metabolite of prulifloxacin, was tested to determine its inhibitory and bactericidal activities against 396 nosocomial and 258 community Italian isolates. Compared with that of ciprofloxacin, its activity (assessed in MIC and minimal bactericidal concentration tests) was generally similar or greater against gram-positive bacteria and greater against gram-negative bacteria. In time-kill assays using selected isolates, its bactericidal activity was comparable to that of ciprofloxacin.

Very low toxicity and good quality of life in 48 elderly patients autotransplanted for hematological malignancies: a single center experience.

Between May 1994 and May 2000, we autotransplanted 48 consecutive patients, 21 females and 27 males aged over 60 years (range: 60-78, median: 63). Sixteen patients had multiple myeloma (MM), 14 high-grade non-Hodgkin's lymphoma (HGNHL), six low-grade non-Hodgkin's lymphoma (LGNHL), nine acute myeloid leukemia (AML), one chronic lymphocytic leukemia (CLL), one Hodgkin's disease (HD) and one breast cancer; the performance status (WHO) was 0-1. Seventeen patients were in 1st CR (35.

A predictive model of varicella-zoster virus infection after autologous peripheral blood progenitor cell transplantation.

Varicella-zoster virus (VZV) frequently causes severe infections in patients who have undergone bone marrow transplantation. The frequency of, characteristics of, and risk factors for this infection were studied in 164 patients undergoing autologous peripheral blood progenitor cell transplantation (PBPCT). Twenty-six patients (15.

A functionally active RARalpha nuclear receptor is expressed in retinoic acid non responsive early myeloblastic cell lines.

Although all-trans retinoic acid (ATRA) can restore the differentiation capacity of leukemic promyelocytes, early leukemic myeloblasts are conversely not responsive to ATRA induced granulocytic differentiation. To assess whether this resistance to ATRA is related to an impaired function of the Retinoic Acid Receptor alpha (RARalpha), we performed an analysis of RARalpha expression and transactivation activity, in several myeloid leukemic cell lines, representative of different types of spontaneous acute myeloid leukemias. Our results indicate that a functionally active RARalpha nuclear receptor is expressed in all the analyzed cell lines, regardless of their differentiation capacity following exposure to ATRA.

SmaI macrorestriction analysis of Italian isolates of erythromycin-resistant Streptococcus pyogenes and correlations with macrolide-resistance phenotypes.

High rates of erythromycin resistance among Streptococcus pyogenes strains have been reported in Italy in the last few years. In this study, 370 erythromycin-resistant (MIC, > or = 1 microg/mL) Italian isolates of this species obtained in 1997-1998 from throat swabs from symptomatic patients were typed by analyzing SmaI macrorestriction fragment patterns by pulsed-field gel electrophoresis (PFGE). Among the typable isolates (n = 341; the genomic DNA of the remaining 29 isolates was not restricted by SmaI), 48 distinct PFGE types were recognized, of which 31 were recorded in only one isolate (one-strain types).

Differentiation of resistance phenotypes among erythromycin-resistant Pneumococci.

Laboratory differentiation of erythromycin resistance phenotypes is poorly standardized for pneumococci. In this study, 85 clinical isolates of erythromycin-resistant (MIC > or = 1 microg/ml) Streptococcus pneumoniae were tested for the resistance phenotype by the erythromycin-clindamycin double-disk test (previously used to determine the macrolide resistance phenotype in Streptococcus pyogenes strains) and by MIC induction tests, i.e.

In vitro activity of ketolides telithromycin and HMR 3004 against italian isolates of Streptococcus pyogenes and Streptococcus pneumoniae with different erythromycin susceptibility.

Two ketolides, telithromycin and HMR 3004, were evaluated for their in vitro activity against erythromycin-susceptible and -resistant strains of Streptococcus pyogenes and Streptococcus pneumoniae. On the basis of their resistance to macrolide, lincosamide and streptogramin (MLS) antibiotics, erythromycin-resistant test strains were assigned to the constitutive resistance (cMLS) phenotype, the inducible resistance (iMLS) phenotype or the M phenotype. iMLS S.

QSAR based on biological microcalorimetry.

In this paper we describe a QSAR based on biological microcalorimetry for a set of antimicrobial hydrazides acting against Saccharomyces cerivisiae and Escherichia coli. Results show that an extrathermodynamic relationship exists based upon partitioning (log P(TA)) and microcalorimetrically measured biopotencies using the same cell systems. Moreover, the extrathermodynamic relationship between drug potencies for these two cell systems shows that both cellular systems appear to behave in the same way with respect to the importance of partitioning.

Amifostine can reduce mucosal damage after high-dose melphalan conditioning for peripheral blood progenitor cellautotransplant: a retrospective study.

Amifostine (WR-2721; Ethyol) is a well-known cytoprotector, but a possible role in preventing extrahaematological toxicity after high-dose therapy (HDT) has never been investigated. We compared two historical groups of patients who either received (group A, n = 35) or did not receive (group B, n = 33) amifostine (740 mg/m2) before high-dose (HD) melphalan, followed by autologous infusion of peripheral blood progenitor cells (PBPCs). Amifostine was well tolerated at this dose level.

Selection and transplantation of autologous CD34+ B-lineage negative cells in advanced-phase multiple myeloma patients: a pilot study.

The feasibility of sequential positive and negative selection of mobilized CD34+ B-lineage negative cells to achieve tumour-free autografts in multiple myeloma (MM) patients was evaluated. Peripheral blood stem cells (PBSC) of 14 patients with advanced disease were mobilized. CD34+ cells were enriched in 12 of the patients by the avidin-biotin immunoabsorption technique.

Infectious complications after autologous peripheral blood progenitor cell transplantation followed by G-CSF.

Infectious complications after autologous peripheral blood progenitor cell transplantation (PBPCT) have been reported in a few studies including small patient numbers. The present study was performed to assess the incidence, types, outcome and factors affecting early and late infections in 150 patients aged 18 to 68 years (median 46.5) who underwent high-dose therapy, with G-CSF.

In vitro activity of levofloxacin against gram-positive bacteria.

The in vitro activity of levofloxacin was investigated against 256 clinical strains of four gram-positive genera (Staphylococcus, Streptococcus, Enterococcus, and Listeria). Ofloxacin and ciprofloxacin were used as comparators. Uniform susceptibility to levofloxacin was recorded among methicillin-susceptible staphylococci, streptococci other than Streptococcus agalactiae, regardless of their being susceptible, intermediate, or resistant to penicillin (S.

Ex vivo pharmacological purging of leukapheresis collections with nitrogen mustard: amifostine pretreatment improves both early and late peripheral blood progenitor cell recovery.

Ex vivo pharmacological purging of bone marrow has been used to eliminate clonogenic tumor cells contaminating the autograft and potentially responsible of relapse. A considerable improvement of pharmacological purging would be achieved only if normal marrow progenitor cells could be selectively protected by the cytotoxicity of these agents. Amifostine (WR-2721; Ethyol), a phosphorylated aminothiol compound, has been shown to have this property both in vivo and in vitro.

Induction of a functional vitamin D receptor in all-trans-retinoic acid-induced monocytic differentiation of M2-type leukemic blast cells.

Different types of acute myeloid leukemia blast cells were induced to differentiate in vitro with all-trans-retinoic acid (ATRA) and vitamin D3 (VD). M0/M1 leukemic cells are not sensitive to differentiating agents, whereas M3 leukemic cells are induced to undergo granulocytic differentiation after ATRA treatment but are not sensitive to VD. M2 leukemic blast cells behave differently because they undergo monocytic differentiation with both the differentiation inducers.

Phenotypes and genotypes of erythromycin-resistant Streptococcus pyogenes strains in Italy and heterogeneity of inducibly resistant strains.

A total of 387 clinical strains of erythromycin-resistant (MIC, >/=1 microg/ml) Streptococcus pyogenes, all isolated in Italian laboratories from 1995 to 1998, were examined. By the erythromycin-clindamycin double-disk test, 203 (52.5%) strains were assigned to the recently described M phenotype, 120 (31.

PBSC mobilization, collection and positive selection in patients with chronic lymphocytic leukemia.

We report the results of PBSC mobilization and immune selection in 17 patients with advanced chronic lymphocytic leukemia (CLL) enrolled in a multicenter Italian study of autologous transplantation with peripheral CD34+ selected cells. Mobilization was achieved by cyclophosphamide (CY) 4 g/m2 + G-CSF 5 microg/kg. CD34+ cells were positively selected by means of avidin-biotin immunoaffinity columns (Ceprate SC) or immunomagnetic beads (Isolex 300i) systems.

Adhesion of water-borne particulates on freshwater biota.

The retention of suspended particles transported by river flow on surfaces of freshwater plants is a potentially important process in the contamination of aquatic biota. Field experiments have been performed to test the role of benthic algae (periphyton) in trapping inorganic suspended solids transported by the river water and to discriminate between the caesium content of periphyton caused by the adherence of inorganic solids and by the active uptake inside the organisms. The contribution of caesium of suspended solids adhering to biotic surfaces was estimated by determining the scandium content (scandium method).

Paroxysmal atrial fibrillation after high-dose melphalan in five patients autotransplanted with blood progenitor cells.

Among the drugs used in conditioning regimens for stem cell transplantation, high-dose melphalan (HDM) plays an important role for both its strong myeloablative effect and for its favourable dose-response ratio. Here we report five cases of high frequency atrial fibrillation (AF) developing after HDM. Duration of the arrhythmia was always very short, beginning at variable intervals after the administration of HDM, in the absence of other factors potentially able to trigger AF.

Factors affecting hemopoietic recovery after high-dose therapy and autologous peripheral blood progenitor cell transplantation: a single center experience.

Background And Objective: While the minimum number of CD34+ cells required for complete and long-lasting engraftment is quite well established, there is not general agreement about the optimal number of CD34+ per kg needed in order to obtain engraftment as rapidly as possible. In the present study we assess factors affecting hemopoietic recovery and the optimal peripheral blood progenitor cell (PBPC) number for rapid engraftment in patients treated with high-dose therapy.

Design And Methods: We enrolled 80 consecutive patients affected by hematologic and non-hematologic malignancies treated with a median of 10 chemotherapy courses (range 3-38).