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C H Jones

Publications and source records attributed to C H Jones.

At least 19 recordsLinked to original sources
PubMed1998

Periplasmic chaperone recognition motif of subunits mediates quaternary interactions in the pilus.

The class of proteins collectively known as periplasmic immunoglobulin-like chaperones play an essential role in the assembly of a diverse set of adhesive organelles used by pathogenic strains of Gram-negative bacteria. Herein, we present a combination of genetic and structural data that sheds new light on chaperone-subunit and subunit-subunit interactions in the prototypical P pilus system, and provides new insights into how PapD controls pilus biogenesis. New crystallographic data of PapD with the C-terminal fragment of a subunit suggest a mechanism for how periplasmic chaperones mediate the extraction of pilus subunits from the inner membrane, a prerequisite step for subunit folding. In addition, the conserved N- and C-terminal regions of pilus subunits are shown to participate in the quaternary interactions of the mature pilus following their uncapping by the chaperone. By coupling the folding of subunit proteins to the capping of their nascent assembly surfaces, periplasmic chaperones are thereby able to protect pilus subunits from premature oligomerization until their delivery to the outer membrane assembly site.

Adhesins, Bacterial↗
PubMed1998

Hemodynamics and survival of patients with acute renal failure treated by continuous dialysis with two synthetic membranes.

Synthetic membranes are not identical and have specific interactions that may be harmful or beneficial. We have investigated the incidence of hypotension and the outcome of acute renal failure (ARF) in ventilated patients treated by continuous venovenous dialysis with 2 different synthetic membranes. In Study 1, the mean arterial pressure (MAP) and systemic vascular resistance (SVR) were monitored during the first 12 min of dialysis with polyacrylonitrile (PAN). In Study 2, the MAP and survival rates were compared in patients randomly assigned to either PAN or polysulfone. No subjects were receiving angiotensin converting enzyme inhibitors. In Study 1, the MAP decreased due to a reduction in the SVR during the first 6 min of dialysis but returned to the baseline value by 12 min in 22 patients during 27 dialysis treatments. In Study 2, the MAP was lower than the baseline value at 6 min during 233 dialysis treatments in 133 patients randomly assigned to PAN or polysulfone membranes (PAN group, 81.5 +/- 15 to 78.7 +/- 15.6 mm Hg, p = 0.001; and polysulfone group, 81.3 +/- 15.4 to 80.0 +/- 15.7 mm Hg, p = 0.06). Severe reductions in the MAP were seen during 13.2% of the PAN and 7.2% of the polysulfone treatments (chi 2, p = NS). The age, APACHE II score, MAP, inotrope requirement, and primary diagnosis did not differ according to membrane material in a total of 197 consecutive patients (PAN, n = 97; polysulfone, n = 100). Patients survival was 29% (PAN) and 27% (polysulfone). In multivariate analysis, APACHE II score, inotrope requirement, and liver failure were significant determinants of survival. In conclusion, PAN and polysulfone membranes were not different with respect to hypotensive reactions or survival in critically ill patients undergoing continuous venovenous hemodialysis.

APACHE↗
PubMed1998

Continuous venovenous high-flux dialysis in multiorgan failure: a 5-year single-center experience.

The objective of this study was to determine the outcome of acute renal failure (ARF) treated by continuous venovenous high-flux dialysis in patients with ventilator-dependent respiratory failure treated in a single center and to examine the importance of primary diagnosis in determining survival. We retrospectively reviewed 408 consecutively treated patients in the multidisciplinary intensive care unit (ICU) of a large teaching hospital. All ventilated patients requiring dialysis support over a 5-year period (January 1, 1991 to December 31, 1995) were included in the study. Patient age, APACHE II score, primary diagnosis, inotrope requirement, and survival to discharge from the ICU, from the hospital, and at 6 months were recorded for 408 consecutively treated patients. The mean age was 54 years, the median APACHE II score was 29, and the ICUs, hospital, and 6-month survival rates were 48%, 38%, and 36%, respectively. Inotropic support was required in 75%. Liver disease was the primary diagnosis in 35%. Logistic regression analysis indicated that increasing age and APACHE II, use of inotropes, and presence of liver disease were all associated with increased mortality. Eight percent of survivors (3% of the total population) required long-term renal replacement therapy. In conclusion, in our experience, continuous venovenous high-flux dialysis can be universally adopted in the ICU management of ARF associated with multiorgan failure. Patient survival is related to primary diagnosis, and a knowledge of case mix is essential in considering outcome of ARF in any reported series.

APACHE↗
PubMed1998

Percentage hypochromic red cells and the response to intravenous iron therapy in anaemic haemodialysis patients.

INTRODUCTION: Iron deficiency is commonly encountered in haemodialysis (HD) patients and may be overcome by i.v. iron therapy. We have examined the percentage hypochromic red cells (%HRC) for predicting response to i.v. iron in subjects with a low serum ferritin. METHODS: Prospective study of i.v. iron saccharate (trivalent iron 200 mg/week for 8 weeks) in anaemic (Hb < 10 g/dl) HD patients with serum ferritin < 100 microg/l despite oral iron therapy. Response to i.v. iron was assessed by comparing Hb at 0 and 8 weeks according to %HRC at baseline (0-3%, 4-9%, > or = 10%). Results are mean+/-1 SD. RESULTS: For all subjects (n=82), Hb and ferritin increased between 0 and 8 weeks (8.9+/-1.0 to 10.1+/-1.4, P<0.0001; 55+/-24 to 288+/-126, P<0.0001). Patients were stratified into three groups according to %HRC at baseline (0-3%, 4-9%, > or = 10%). Hb increased significantly in all three groups. The mean increase in Hb was greater (0-3%, 0.6+/-1.2; 4-9%, 1.2+/-1.0; > or = 10%, 1.6+/-1.4; P=0.02) and the proportion of patients showing a > or = 1 g/dl increase in Hb was greater (0-3%, 27%; 4-9%, 57%; > or = 10%, 67%; P=0.02) in those with the largest %HRC pre-treatment. CONCLUSION: Intravenous iron therapy is effective in improving Hb in anaemic HD patients with a low ferritin. However, the magnitude of this response and the proportion of patients responding is related to the percentage hypochromic red cells prior to treatment.

Anemia↗
PubMed1998

Extracellular fluid volume determined by bioelectric impedance and serum albumin in CAPD patients.

AIM: To investigate the relationship between serum albumin and extracellular fluid volume, as measured by multifrequency bioelectrical impedance, in stable patients treated by CAPD. METHOD: Fifty-nine stable CAPD patients were assessed. Serum albumin (bromocresol green) and CRP, age, dialysate to plasma (D/P) creatinine ratio, normalized protein catabolic rate (nPCR), daily urine and peritoneal protein losses, and extracellular fluid volume (Vecf) were measured in each patient. Vecf was calculated as a percentage of actual body weight (Vecf% ABW), of lean body mass derived from anthropometry (Vecf% LBM) and of total body water (Vecf% Vtbw). Comparisons between those with a normal serum albumin (> or = 37 g/l) and those with a low serum albumin (< 37 g/l) were made by Mann-Whitney U test. Correlations with serum albumin were sought by Pearson's test. RESULTS: The D/P creatinine ratio, daily peritoneal and urine protein losses, and extracellular fluid volume (Vecf% LBM and Vecf% Vtbw) were all significantly greater in patients with serum albumin < 37 g/l as compared to those > or = 37 g/l; P < 0.05. Age, CRP, and nPCR were not different. Serum albumin was negatively correlated with Vecf% LBM, r = -0.25; P = 0.05, Vecf% Vtbw, r = -0.39; P = 0.002, and daily urinary albumin loss, r = -0.25, P = 0.06. CONCLUSION: Hypoalbuminaemia is partly dependent on subclinical overhydration in CAPD patients. Serum albumin is negatively correlated with increased extracellular fluid volume and the proportion of Vecf to Vtbw is increased in hypoalbuminaemic patients. Multifrequency bioelectrical impedance is able to identify these abnormalities.

Adult↗
PubMed1997

The chaperone-assisted membrane release and folding pathway is sensed by two signal transduction systems.

The assembly of interactive protein subunits into extracellular structures, such as pilus fibers in the Enterobacteriaceae, is dependent on the activity of PapD-like periplasmic chaperones. The ability of PapD to undergo a beta zippering interaction with the hydrophobic C-terminus of pilus subunits facilitates their folding and release from the cytoplasmic membrane into the periplasm. In the absence of the chaperone, subunits remained tethered to the membrane and were driven off-pathway via non-productive interactions. These off-pathway reactions were detrimental to cell growth; wild-type growth was restored by co-expression of PapD. Subunit misfolding in the absence of PapD was sensed by two parallel pathways: the Cpx two-component signaling system and the sigma E modulatory pathway.

Adhesins, Escherichia coli↗
PubMed1997

Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination.

Virtually all uropathogenic strains of Escherichia coli, the primary cause of cystitis, assemble adhesive surface organelles called type 1 pili that contain the FimH adhesin. Sera from animals vaccinated with candidate FimH vaccines inhibited uropathogenic E. coli from binding to human bladder cells in vitro. Immunization with FimH reduced in vivo colonization of the bladder mucosa by more than 99 percent in a murine cystitis model, and immunoglobulin G to FimH was detected in urinary samples from protected mice. Furthermore, passive systemic administration of immune sera to FimH also resulted in reduced bladder colonization by uropathogenic E. coli. This approach may represent a means of preventing recurrent and acute infections of the urogenital mucosa.

Adhesins, Bacterial↗
PubMed1997

Serum albumin and survival in CAPD patients: the implications of concentration trends over time.

HYPOTHESIS: Trends in serum albumin concentration over time provide a better prediction of clinical outcome in CAPD patients than a single mean value. METHODS: This was a retrospective review of outcome at 36 months in 225 adult CAPD patients. Mean serum albumin was determined for the first (SA1) and second (SA2) 6 months of treatment and patients grouped according to SA1 (group I, > 37; group II, 34-37; group III, < 34 g/l) and according to the change in serum albumin (delta SA) between the first and second 6 months (increased/static or decreased). Patient (PS) and technique (TS) survival were determined by Kaplan-Meier survival analysis. The effect of SA1 and delta SA on survival were determined in a multivariate Cox regression analysis model that included age and presence or absence of a systemic disease. RESULTS: By SA1 group, PS and TS survival at 36 months were 94 and 76% (group I), 64 and 53% (group II) and 70 and 52% (group III). If delta SA increased/remained static, then SA1 did not predict PS (group I, 100%; group II, 96%; group III, 74%; P = n.s.) or TS (group I, 72%; group II, 63%; group III, 65%; P = n.s.). If delta SA decreased, PS was worse in groups II and III, both as compared to group I (PS group I, 88%; group II, 52%; group III, 34%; P = 0.02) and as compared to the groups II and III when delta SA increased (PS group II, 74 vs 52%, P = 0.05; group III, 82 vs 34%, P = 0.005) The same trend was seen for TS. In the multivariate Cox regression model, age, direction of change in serum albumin, and presence of a multisystem disease were significant predictors of survival, whereas SA1 was not. CONCLUSION: Early hypoalbuminaemia in CAPD only predicts a worse patient and technique survival if mean serum albumin decreases further from the first to second 6 months of dialysis therapy. Change in serum albumin between the first and second 6 months of CAPD and the mean serum albumin over the first 6 months together offer better discrimination of outcome than either alone.

Adult↗
PubMed1997

Assessment of nutritional status in CAPD patients: serum albumin is not a useful measure.

INTRODUCTION: In CAPD patients serum albumin is frequently used as an index of nutritional status, although it is recognized that hypoalbuminaemia may be caused by many factors. We have further examined the relationship between serum albumin and nutrition. METHODS: Nutritional status was assessed by biochemistry, anthropometry, mid-arm muscle circumference, muscle strength (hand grip and back), and lean body mass (from anthropometry, creatinine kinetics and bioimpedance) in a group of 76 stable CAPD patients. Correlations between biochemical and nutritional parameters were sought and data were compared between patient groups defined by serum albumin (> or = 37 vs < 37 g/l on two occasions 2 months apart) and separately according to subjective global assessment score (normal nutrition, A vs mild to moderate, B, and severe, C, malnutrition). RESULTS: In patients with a low SGA score, actual body weight, body mass index, mid-arm muscle circumference, lean body mass, subscapular skinfold thickness, hand grip strength (males and females) and iliac and triceps skinfold thicknesses and back strength (females only) were all significantly less than in patients with a normal SGA score. In contrast, none of these variables differed in either gender when patients were compared according to serum albumin. Serum albumin was correlated with serum creatinine (r = 0.45, P = 0.01), daily urine protein excretion (r = -0.42, P = 0.02) and uncorrected weekly creatinine clearance (r = -0.39) in females, but not with any index of body composition in either gender. CONCLUSION: Whilst SGA identified a patient group with significantly abnormal body mass, muscle mass and muscle strength, serum albumin did not. Serum albumin is not a useful marker of malnutrition in stable patients on CAPD.

Adolescent↗