STAT6 and STAT1 are essential antagonistic regulators of cell survival in classical Hodgkin lymphoma cell line.

Classical Hodgkin lymphoma (cHL) is a malignant lymphoid disorder characterized by aberrant activation of signaling pathways. Constitutive activation of several components of the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway has been observed in Hodgkin and Reed/Sternberg cells, the tumor cells of cHL. In this study, we investigate the function of STAT6 in cHL cell lines and show that STAT6 promotes survival of these cells. Microarray expression analysis of STAT6-shRNA (short hairpin RNA)-expressing cHL cell lines was carried out to analyze the STAT6-mediated survival mechanism. Some of the identified genes with potentially important regulatory functions were also interleukin (IL)-4 dependently regulated in Ramos B cells and binding of STAT6 to the regulatory regions of several genes could be confirmed, indicating that these are direct STAT6 target genes. Importantly, STAT6 knockdown increased the expression and activation of STAT1 as well as the expression of known STAT1 target genes, indicating a cross-regulation between these signaling molecules. Forced expression of STAT1 was able to induce apoptosis in cHL cell line L1236. These findings indicate that both STAT6 and STAT1 can act as important antagonistic regulators in the pathogenesis of cHL.

Influence of subinhibitory concentrations of amikacin and ciprofloxacin on morphology and adherence ability of uropathogenic strains.

The influence of subinhibitory concentrations (1/2, 1/4, 1/8, 1/16 and 1/32 MIC) of amikacin and ciprofloxacin on the morphology and adherence of uropathogenic strains was studied. Intensity of morphological changes was proportional to the concentrations of these antibiotics. Morphological changes were the most prominent after bacterial exposure to sub-MICs of ciprofloxacin. These concentrations, especially 1/2 MIC of ciprofloxacin, induced the formation of filaments of E. coli, K. pneumoniae, K. oxytoca, E. cloacae and A. calcoaceticus biotype anitratus. No morphological changes were observed in P. aeruginosa, S. epidermidis and S. aureus cells after exposure to subinhibitory concentrations of both antibiotics. Sub-MICs of amikacin affected the changes in cell shape only slightly. The exposure of bacterial strains to 1/2 MIC of ciprofloxacin induced increased vacuolation of the cells. We observed shrinkage of the protoplasm and the pleated cell walls in comparison with control cells. The greatest loss of adherence ability occurred at 1/2 MIC of ciprofloxacin after a 1-d incubation.

The mechanisms of activation of normal human serum complement by Escherichia coli strains with K1 surface antigen.

Ten E. coli K1 strains isolated from the urine of children with urinary tract infections were sensitive to the bactericidal action of normal human serum (NHS). The role of the particular mechanisms of complement activation was determined in the process of killing these strains, showing variable sensitivity to the bactericidal action of NHS; three mechanisms of activation of human complement were observed. Important role of alternative pathway activation in the bactericidal action of NHS against E. coli K1 strains independent of the classical and lectin pathways was not established.

The sensitivity of escherichia coli strains with K1 surface antigen and rods without this antigen to the bactericidal effect of serum.

The susceptibility of Escherichia coli strains with K1 surface antigen (K1+) and rods without this antigen (K1-) to the bactericidal action of normal bovine serum and human normal cord serum was determined. Seventy E. coli strains (35 K1+ and 35 K1-) were isolated from urine obtained from children with urinary tract infections. The strains investigated showed variable sensitivity to the bactericidal action of the sera. E. coli K1+ strains were characterized by lower sensitivity to bactericidal effect of the sera in comparison with K1- rods. The role of the particular mechanisms of complement activation in the process of killing of the E. coli strains was also determined.

[Etiological factors of urinary tract infections in children]. / Czynniki etiologiczne zakazen ukladu moczowego u dzieci.

Etiological factors of urinary tract infection in children have been studied. The Escherichia coli, Klebsiella sp., Enterococcus sp. and Enterobacter sp. were the most often isolated bacteria from infant and baby urine. In this age group of patients uromycoses were also affirmed. From the urine of older children (1-18 years old) mainly Escherichia coli, Enterococcus sp., Proteus sp. and Morganella morganii have been raised. Uropathogens' occurrence was analysed by a statistical method in the relation to age and sex of the children. The girls in the age of 1 to 18 years were more open than boys to urinary tract infections caused by Escherichia coli and less open to infections caused by Morganella morganii and Enterococcus sp.

[Nonspecific adhesion of Staphylococcus aureus strains to solid surfaces]. / Niespecyficzna przyczepnosc komórek Staphylococcus aureus do powierzchni stalych.

Autoagregating strains of bacteria are characterised by high surface hydrophobicity, which determines their ability to adhesion. An assessment was done of non-specific adhesion to solid surfaces of S. aureus strains isolated from blood, pus and nasopharynx of hospitalised people. The method used made possible differentiation of strains, which were studied, on the basis of their surface characteristics. Their properties decide about the abilities of strains to the colonisation of host tissues and at the same time they influence their potential virulence. In the study attention was also paid to the participation of surface proteins in the processes of adhesion cells to glass surfaces.

[Infectivity and resistance to antibiotics of uropathogenic gram-negative rods]. / Wystepowanie i wrazliwosc na leki uropatogennych paleczek Gram-ujemnych.

The nature of bacterial isolates from children with clinically suspected urinary tract infections (UTI) was studied. The susceptibility of urinary pathogens to selected antibiotics was determined. The results clearly show that E. coli was identified as the main causative agent of UTI children (67% of isolates). The second commonest pathogen was P. mirabilis (10%). Over half E. coli isolates were resistant to amino-penicilins but almost all isolates (over 80%) were sensitive to antimicrobial agents combined with beta-lactamase inhibitors. We found significantly high percentage (32.5%) of ESBL strains among K. pneumoniae isolates.

Catechol-O-methyltransferase inhibition attenuates levodopa toxicity in mesencephalic dopamine neurons.

Inhibition of catechol-O-methyltransferase (COMT; EC 2.1.1.6) is a new therapeutic strategy in the treatment of Parkinson's disease. However, nothing is known about the effects of COMT inhibition on levodopa (L-dopa)-induced toxicity in dopamine (DA) neurons. Therefore we evaluated the effects of the selective COMT inhibitors Ro 41-0960, OR-486, and tolcapone alone and in combination with L-dopa in primary mesencephalic cultures from rat. Neither COMT inhibitor affected the growth of tyrosine hydroxylase immunoreactive (THir) cells with concentrations up to 10 microM when studied alone. However, Ro 41-0960 reduced the L-dopa-induced THir cell loss after 24 h in a dose-dependent manner, shifting the TD(50) value from 21 microM in the absence to 71 microM in the presence of 1 microM Ro 41-0960 (P <.01) without affecting survival of non-DA neurons. OR-486 and the clinically used COMT inhibitor tolcapone showed similar effects. In contrast, toxicity induced by D-dopa was not altered by COMT inhibitors. Furthermore, the primary metabolite of L-dopa formed by COMT, 3-O-methyldopa, and the methyl group donor S-adenosyl-L-methionine used by COMT did not alter THir neuron survival and L-dopa-induced toxicity, respectively, with concentrations up to 100 microM. These data demonstrate that COMT inhibition attenuates L-dopa toxicity toward DA neurons in vitro, but probably not by preventing 3-O-methyldopa production or cellular S-adenosyl-L-methionine depletion.

Synergistic bactericidal effect of cephalexin and normal cord serum (NCS) against Escherichia coli K1 strains isolated from children with urinary tract infections (UTI).

Investigations were performed on the bactericidal activity of cephalexin (keflex) and normal cord serum (NCS) against Escherichia coli K1 strains isolated from UTI. A synergistic interaction of the antibiotic and NCS was found against the strains resistant and sensitive to the serum.

Exploring the lived-experience of childhood cancer survivors.

The purpose of this qualitative phenomenological study was to explore the lived-experience of childhood cancer survivors with regard to their patterns of interaction with family and the environment using Newman's theory of Health as Expanding Consciousness, which proposes that experiencing a devastating event promotes an expanded consciousness. The sample consisted of five young adults, ages 23 to 26 years, who had experienced childhood cancer and now are considered to be cured of their initial cancer. A hermeneutic dialectic approach was used, with each subject being asked to respond to one open-ended question, "What are the most meaningful events in your life?" The interviews were analyzed for evidence of expanded consciousness, changing relatedness, and other universal themes. Individual patterns emerged and themes were identified that supported Newman's theory, such as optimism and hope, stronger bonds to family and friends, increased capacity for empathy, a desire to help others, and deeper feelings for the value of life. The intensely personal and professional relationship that develops between pediatric oncology nurses and their patients can only be strengthened by the knowledge that these patients generally grew up to be caring and empathetic individuals, perhaps as a result of the nurses' loving care for them. This research also provided support for Newman's theory as a sound paradigm for nursing practice.

The susceptibility of gram-negative rods and their adaptive forms resistant to colistine to the bactericidal action of sera.

The susceptibility of Escherichia coli K1, Salmonella enteritidis, Salmonella typhimurium strains and their adaptative forms resistant to colistine (Colr forms) was compared with respect to their sensitivity to the bactericidal action of normal cord serum and normal bovine serum. It has been shown that the Colr forms are more susceptible to sera as compared to initial strains. The increase of sensitivity of the Colr forms is connected with structural changes within bacterial cell wall which is the target for complement as well as for colistine.

Changes in ionized calcium concentrations and acid-base status during abdominal aortic vascular surgery.

Abdominal aortic surgery may produce significant haemodynamic instability (from a combination of factors: hypovolaemia, acid-base disturbances, vasoactive metabolite release from ischaemic tissues and hypocalcaemia). Calcium is often given after aortic unclamping to attenuate this instability. We studied 20 patients undergoing elective abdominal aortic surgery and observed a triphasic change in ionized calcium concentrations and acid-base status. Initially, during the cross-clamp period (when patients were cardiovascularly stable), ionized calcium concentrations decreased significantly (mean 1.06 (SD 0.08) to 0.91 (0.13) mmol litre-1; P < 0.01), while a significant metabolic acidosis developed (pH 7.38 (0.05) to 7.30 (0.05); P < 0.05). Second, release of the aortic cross-clamp resulted in further acidosis (pH 7.27 (0.05) (P < 0.05) mixed respiratory and metabolic) with a decrease in mean arterial pressure, with no change in ionized calcium concentrations. The third phase was associated with spontaneous restoration of acid-base status and ionized calcium concentrations to normal over 2 h. There was no correlation between units of blood given, volume of blood lost, fluid volume given or duration of aortic cross-clamping and degree of ionized hypocalcaemia. We conclude that ionized hypocalcaemia occurred during the cross-clamp period of aortic surgery, was unrelated to the volume of blood given and did not appear to be responsible for the changes in arterial pressure during surgery.

[Hydrophobic properties of Pseudomonas aeruginosa strains]. / Hydrofobowe wlasciwosci szczepów Pseudomonas aeruginosa.

Hydrophobic properties are considered as a factor enhancing the adhesion of bacteria to tissue cells. The strains of P. aeruginosa isolated from patients with urinary tract infections (UTI), from feces and soil were investigated. It shows that over 50% strains isolated from UTI had hydrophobic cell surface. Most of all strain investigated (67.9%) is characterized by hydrophobicity what probably favours their pathogenicity.

Blood interleukin 10 levels parallel the severity of septic shock.

PURPOSE: The aim of this study was to investigate the relation between interleukin (IL) 10, tumor necrosis factor alpha (TNF alpha), IL-1, and IL-6 levels in patients with septic shock and relate these cytokine levels to the development of organ failure. PATIENTS AND METHODS: In 11 patients with septic shock of recent onset, blood was sampled for determinations of TNF, IL-1, IL-6, and IL-10. The degree of organ failure was scored for four organ systems (respiratory, hepatic, renal, hematologic) in the first 48 hours of the study. RESULTS: The APACHE II score was 21 +/- 4. Three patients died. IL-10 levels were directly correlated with TNF levels (r = 0.73, P < .05) and IL-6 levels (r = 0.67, P < .05); and inversely correlated with total C3 (r = -0.73, P < .05) and CH50 (r = -0.68, P < .05). Both IL-10 and TNF levels were correlated to the organ failure score (r = 0.75 and r = 0.68, both P < .01). Six patients with high IL-10 levels (> 60 pg/mL) had lower C3 (37 +/- 11 v 62 +/- 10 mg/dL) and CH50 (32 +/- 7 v 68 +/- 19%), and higher organ failure scores (5.7 +/- 0.8 v 3.8 +/- 1.3) than those with low IL-10 levels (all P < .05). CONCLUSION: Although IL-10 has an inhibitory effect on the production of cytokines, it is released together with TNF and IL-6 in patients with septic shock. IL-10 blood levels are directly related to the severity of inflammation and the development of organ failure in septic shock.

Social support networks of confidants to people with AIDS.

AIDS has a devastating impact on the social support networks of those most closely involved with the person with AIDS (PWA). This qualitative study of the social support networks of confidants to PWAs reports the findings of intensive, semistructured interviews with 11 confidants. Numerous changes were observed in the confidants' supportive resources, network structure, and functioning. Implications for social work practice are discussed.

Administration of an antibody to E-selectin in patients with septic shock.

OBJECTIVES: To determine the safety and pharmacokinetics of a murine monoclonal antibody to E-selectin in patients with newly developed septic shock. DESIGN: Open-label, prospective, phase II pilot study with escalating doses of the antibody. SETTING: Intensive care unit of a 900-bed university hospital. PATIENTS: Nine patients who survived the first 24 hrs of septic shock. INTERVENTIONS: In addition to standard therapy, an intravenous bolus of a murine monoclonal antibody to E-selectin, CY1787, was given at doses of 0.1 mg/kg (n = 3), 0.33 mg/kg (n = 3), and 1.0 mg/kg (n = 3). MEASUREMENTS AND MAIN RESULTS: CY1787 was well tolerated in all patients. Signs of shock resolved in all patients, and organ failure entirely reversed in eight patients. All patients survived the 28-day follow-up. Administration of CY1787 was associated with an early and brisk increase in PaO2/FIO2 ratio (p < .001), from 146 +/- 38 mm Hg (19.5 +/- 5.1 kPa) to 205 +/- 45 mm Hg (27.3 +/- 6.0 kPa) after 2 hrs, and 250 +/- 58 mm Hg (33.3 +/- 7.7 kPa) after 12 hrs. A dose-related effect of CY1787 was suggested by an earlier weaning from catecholamine therapy and a faster resolution of organ failure in the high-dose group. Development of antimouse antibodies was documented in eight patients. CONCLUSIONS: This pilot study indicates that this antibody to E-selectin appears to be safe and may represent a promising form of therapy in septic shock.