Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors

We used plants as an in vivo pathogenesis model for the identification of virulence factors of the human opportunistic pathogen Pseudomonas aeruginosa. Nine of nine TnphoA mutant derivatives of P. aeruginosa strain UCBPP-PA14 that were identified in a plant leaf assay for less pathogenic mutants also exhibited significantly reduced pathogenicity in a burned mouse pathogenicity model, suggesting that P. aeruginosa utilizes common strategies to infect both hosts. Seven of these nine mutants contain TnphoA insertions in previously unknown genes. These results demonstrate that an alternative nonvertebrate host of a human bacterial pathogen can be used in an in vivo high throughput screen to identify novel bacterial virulence factors involved in mammalian pathogenesis.     

Physiological and perceptual features of dysarthria in Moebius syndrome: directions for treatment

The functioning of the major subsystems of the speech production apparatus of a 12 year old female with Moebius syndrome was investigated using a battery of perceptual and physiological instrumental measures. Perceptual tests administered included: The Assessment of Intelligibility of Dysarthric Speech; the Frenchay Dysarthria Assessment; and a perceptual analysis of a speech sample based on a reading of the Grandfather Passage. Instrumental procedures included: spirometric and kinematic analysis of speech breathing; electroglottographic and aerodynamic evaluation of laryngeal function; nasometric assessment of velopharyngeal function; and evaluation of lip and tongue function using a variety of strain-gauge and pressure transducers. Consistent with the pathophysiological basis of Moebius syndrome, the major dysfunctions of the speech production mechanism were found at the level of the articulatory valve. Somewhat unexpectedly, however, impaired function was also identified at the level of the velopharyngeal and laryngeal valves by both the perceptual and instrumental assessments and at the level of the respiratory system by the physiological analysis alone. The results are discussed with reference to the neurological basis and clinical features of Moebius syndrome. The implications of the findings for the treatment of congenital dysarthria associated with Moebius syndrome are also discussed. The advantage of instrumental analysis over perceptual assessments in defining treatment goals for children with congenital dysarthria is highlighted.     

Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls

PURPOSE: To assess the computed tomographic (CT) and histologic findings of intrathoracic lymphoproliferative disease (LPD) associated with the Epstein-Barr virus (EBV). MATERIALS AND METHODS: The authors retrospectively reviewed the CT scans of the chest and the pathologic specimens obtained in 24 patients with histologically proved intrathoracic LPD and with positive serologic findings or immunohistochemical staining for EBV. Five patients had acquired immunodeficiency syndrome (AIDS); one had common variable immune deficiency; and 18 were receiving immunosuppressive therapy for heart, lung, or heart-lung (n =15) or bone marrow (n = 2) transplantation and vasculitis (n = 1). RESULTS: Final diagnoses included malignant lymphoma (n = 15), polyclonal LPD (n = 8), and hyperplasia of bronchus-associated lymphoid tissue (n = 1). CT findings included multiple nodules (n = 21), lymphadenopathy (n = 9), areas of groundglass opacification (n = 8), septal thickening (n = 7), consolidation (n = 5), pleural effusion (n = 4), and solitary endobronchial lesion (n = 2). The nodules were 2-4 cm in diameter, involved mainly the middle and lower lung zones, and frequently had a predominantly peribronchovascular (n = 15) or subpleural (n = 14) distribution. CONCLUSION: EBV-associated LPD may range from benign lymphoid hyperplasia to high-grade lymphoma. The most common CT manifestation consists of multiple nodules, frequently in a predominantly peribronchovascular or subpleural distribution.     

Changes in bone mineral density, body composition, and lipid metabolism during growth hormone (GH) treatment in children with GH deficiency

Adults with childhood onset GH deficiency (GHD) have reduced bone mass, increased fat mass, and disorders of lipid metabolism. The aim of the present study was to evaluate bone mineral density (BMD), bone metabolism, body composition, and lipid metabolism in GHD children before and during 2-3 yr of GH treatment (GHRx). Forty children with GHD, mean age 7.9 yr, participated in the study of bone metabolism and body composition; and an additional group of 17 GHD children, in the study of lipid metabolism. Lumbar spine BMD, total body BMD, and body composition were measured with dual-energy x-ray absorptiometry. Volumetric BMD (bone mineral apparent density, BMAD) was calculated to correct for bone size. BMD, BMAD, lean tissue mass, bone mineral content, fat mass, and percentage body fat were expressed as SD scores (SDS), in comparison with normative data of the same population. Lumbar spine BMD and BMAD and total body BMD were all decreased at baseline. All BMD variables increased significantly during GHRx, lumbar spine BMD SDS, already after 6 months of treatment. Lean tissue mass SDS increased continuously. Bone mineral content SDS started to increase after 6 months GHRx. Fat mass SDS decreased during the first 6 months of GHRx and remained stable thereafter. Biochemical parameters of bone formation and bone resorption did not differ from normal at baseline and increased during the first 6 months of GHRx. Serum 1,25 dihydroxyvitamin D increased continuously during GHRx, whereas PTH and serum calcium remained stable. Lipid profile was normal at baseline: Atherogenic index had decreased and apolipoprotein A1(Apo-A1) had increased after 3 yr of treatment. In conclusion, children with GHD have decreased bone mass. BMD, together with height and lean tissue mass, increased during GHRx. GHRx had a beneficial effect on lipid metabolism.     

Chronic energy deficiency in women from rural Bangladesh: some socioeconomic determinants

In this study, five different bacteria with their different strains were isolated and characterized. Contact angles were measured by a captive-bubble technique. Surface-free energies were calculated from the contact angles. Hydrophobicities also were evaluated by rho-xylene adhesion. The zeta potentials and surface charges of the bacteria were obtained. The contact angles of the gram-positive bacteria and gram-negative bacteria were within the range of 48 degrees-69 degrees and 43.5 degrees-55 degrees, respectively, while corresponding surface-free energies were in the limits of 45.4-51.6 erg/cm-2 and 51.7-61.8 erg/cm-2, respectively. The rho-xylene adhesions were parallel to hydrophobicities defined by contact angles, and 32.2-80.3% and 2.3-36.6% for the gram-positive bacteria and gram-negative bacteria, respectively. The zeta potentials for these bacteria were from -650.2 to +17.5 mV and from -159.6 to -6.0 mV, respectively. Most of the bacteria were negatively charged, except the CNS-2 and CPS-1 strains. In the second part of the study, attachment of these bacteria to Vicryl sutures and their DMAEMA and AAc plasma-treated forms were investigated. Hydrophobic bacteria attached more to hydrophobic Vicryl sutures. Both plasma treatments caused significant drops in bacterial attachment in most cases. Effects of AAc plasma treatment were more pronounced.     

The glycine site of the NMDA receptor contributes to neurokinin1 receptor agonist facilitation of NMDA receptor agonist-evoked activity in rat dorsal horn neurons

Resistance measurements are the most useful parameters for assessing acute changes in airway caliber associated with bronchodilation or bronchial provocation. Used in addition to spirometry, Raw can provide a better differentiation of the causes of airflow impairment as well as the presence of concurrent processes. A simple, noninvasive Raw measurement can provide definitive answers in the absence of other changes. Finally, the addition of practical, nonplethysmographic measurements opens a new application for bedside, office, and home monitoring.     

Nitric oxide: description of a pipeline delivery system

The effect of azelastine hydrochloride (azelastine) on synthesis and release of platelet activating factor (PAF) in alveolar macrophages obtained from asthmatic and non-asthmatic subjects was examined. Alveolar macrophages (AMs) were preincubated with or without azelastine and stimulated with f-Met-Leu-Phe (fMLP, 10 microM) for 15 min. PAF activity was detected by aggregation of washed guinea pig platelets. PAF activity released from alveolar macrophages (AMs) from asthmatics without preincubation of azelastine was 15.97 [2.17] (mean [SD], ng/10(7) cells) in supernatants and 42.52 [10.16] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of azelastine, PAF activity reduced to 10.71 [2.73] (mean [SD], ng/10(7) cells), 7.86 [0.94], and 3.52 [0.31] in the supernatants, and 35.58 [7.37], 21.57 [4.36], and 14.77 [0.99] (n = 15) in the cell pellets, respectively. PAF activity in non-asthmatic subjects without preincubation of azelastine was 8.55 [1.16] (mean [SD], ng/10(7) cells) in supernatants and 32.64 [3.37] in cell pellets. After preincubation with 10(-8), 10(-6), and 10(-4) M of azelastine, PAF activity reduced to 6.68 [0.78] (mean [SD], ng/10(7) cells), 4.47 [0.51], and 2.97 [0.36] in the supernatants, and 29.53 [3.75], 14.78 [1.95], and 6.16 [0.55] (n = 20) in the cell pellets, respectively. Our results showed that preincubation with azelastine caused a dose-dependent inhibition of intra- and extracellular PAF activity from asthmatic and non-asthmatic macrophages in the same manner.