Biomedical subjects

Shu-Cheng Chen

Publications and source records attributed to Shu-Cheng Chen.

26 records · Page 2Linked to original sources

PubMed2002

Transient lung-specific expression of the chemokine KC improves outcome in invasive aspergillosis.

Invasive aspergillosis is a common and devastating pneumonia in immunocompromised hosts. Neutrophils are critical for defense against this infection, and ELR+ CXC chemokines are potent neutrophil chemoattractants. We hypothesized that transient lung-specific overexpression of one such ligand, KC, in mice with invasive aspergillosis improves the outcome of disease. We generated mice in which transgenic expression of KC was limited to the lungs and occurred only upon exposure to tetracycline analogues, and we exposed them to doxycycline after the onset of invasive aspergillosis. Transgenic mice had a threefold greater survival, a 74% lower lung fungal burden, a greater magnitude of lung KC induction, and an earlier and higher peak of lung neutrophil influx compared with wild-type mice. In addition to a higher number of neutrophils, we found a 1.8-fold higher number of monocytes-macrophages in the lungs of transgenic mice as compared with wild-type mice. Furthermore, transgenic mice had greater lung expression of interferon-gamma and interleukin-12 in response to infection, suggesting that transgenic expression of KC indirectly regulated the expression of other cytokines associated with improved host defense against this pathogen. Taken together, these data suggest that overexpression of KC in the lung in the setting of established invasive aspergillosis results in improved host defense and outcome of disease.

Animals↗

PubMed2002

Ectopic expression of the murine chemokines CCL21a and CCL21b induces the formation of lymph node-like structures in pancreas, but not skin, of transgenic mice.

The CC chemokine CCL21 is a potent chemoattractant for lymphocytes and dendritic cells in vitro. In the murine genome there are multiple copies of CCL21 encoding two CCL21 proteins that differ from each other by one amino acid at position 65 (either a serine or leucine residue). In this report, we examine the expression pattern and biological activities of both forms of CCL21. We found that although both serine and leucine forms are expressed in most tissues examined, the former was the predominant form in lymphoid organs while the latter was predominantly expressed in nonlymphoid organs. When expressed in transgenic pancreas, both forms of CCL21 were capable of inducing the formation of lymph node-like structures composed primarily of T and B cells and a few dendritic cells. Induction of lymph node-like structures by these CCL21 proteins, however, could not be reproduced in every tissue. For instance, no lymphocyte recruitment or accumulation was observed when CCL21 was overexpressed in the skin. We conclude that both forms of CCL21 protein are biologically equivalent in promoting lymphocyte recruitment to the pancreas, and that their ability to induce the formation of lymph node-like structures is dependent on the tissues in which they are expressed.

Animals↗

PubMed2002

Central nervous system inflammation and neurological disease in transgenic mice expressing the CC chemokine CCL21 in oligodendrocytes.

To study the biological role of the chemokine ligands CCL19 and CCL21, we generated transgenic mice expressing either gene in oligodendrocytes of the CNS. While all transgenic mice expressing CCL19 in the CNS developed normally, most (18 of 26) of the CCL21 founder mice developed a neurological disease that was characterized by loss of landing reflex, tremor, and ataxia. These neurological signs were observed as early as postnatal day 9 and were associated with weight loss and death during the first 4 wk of life. Microscopic examination of the brain and spinal cord of CCL21 transgenic mice revealed scattered leukocytic infiltrates that consisted primarily of neutrophils and eosinophils. Additional findings included hypomyelination, spongiform myelinopathy with evidence of myelin breakdown, and reactive gliosis. Thus, ectopic expression of the CC chemokine CCL21, but not CCL19, induced a significant inflammatory response in the CNS. However, neither chemokine was sufficient to recruit lymphocytes into the CNS. These observations are in striking contrast to the reported activities of these molecules in vitro and may indicate specific requirements for their biological activity in vivo.

Animals↗

PubMed2002

Peritoneal and hemodialysis: I. Differences in patient characteristics at initiation.

BACKGROUND: Comparisons of mortality outcomes between peritoneal dialysis (PD) and hemodialysis (HD) patients have shown varying results, which may be caused by the unequally distributed clinical conditions of patients at initiation. To address this issue, we evaluated the clinical characteristics of 105,954 patients at the initiation of PD and HD, using the U.S. national incidence data on treated end-stage renal disease from the Medical Evidence Form, 1995 to 1997. METHODS: A general linear model was used to analyze differences of age, albumin, creatinine, blood urea nitrogen (BUN), and hematocrit; categorical data analysis to evaluate body mass index (BMI), grouped into four categories: < 19, 19-25 (< 25), 25-30 (< 30), and 30+; and logistic regression to assess the likelihood of initiating PD versus HD. Diabetics (DM) were analyzed separately from non-diabetics (NDM). Explanatory variables in the logistic regression included incidence year, race, gender, age, BMI, albumin, creatinine, BUN, and hematocrit. Race included white and black. Age was categorized into four groups: 20-44, 45-64, 65-74, and 75+. RESULTS: At the initiation of dialysis PD patients were approximately 6 years younger (P < 0.0001) than HD patients. PD patients also had higher (P < 0.0001) albumin (+0.35 g/dL for DM and +0.23 g/dL for NDM) and hematocrit (+1.64% for DM and +1.71% for NDM) levels, and lower (P < 0.04) BUN (-8.75 mg/dL for DM and -5.24 mg/dL for NDM) and creatinine (-0.51 mg/dL for DM and -0.23 mg/dL for NDM) levels than HD patients. Whites had a higher (P < 0.0001) likelihood of starting PD than blacks, and patients with BMI <19 had a lower (P < 0.0001) chance of beginning on PD. CONCLUSION: PD patients had favorable clinical conditions at the initiation of dialysis, which should be taken into consideration when comparing dialysis outcomes between the two modalities.

Adult↗

PubMed2002

Peritoneal and hemodialysis: II. Mortality risk associated with initial patient characteristics.

BACKGROUND: Patients initiating with peritoneal dialysis (PD) have favorable clinical conditions compared with hemodialysis (HD) patients, which may contribute to the varying results found in studies of mortality across the two therapies. METHODS: National incidence data of end-stage renal disease patients from 1995 to 1997 were used, excluding the first 90 days of treatment and including all patients who were on either PD or HD on day 91. Patients were then followed for a one-year period. A Cox proportional hazards regression analysis was used, separating diabetics and non-diabetics, and two statistical models were applied. Model 1 included race, gender, age, initial modality, and incidence year as explanatory variables. Model 2 added body mass index (BMI), initial levels of serum albumin, creatinine, and blood urea nitrogen. RESULTS: Age was most highly associated with mortality, followed by biochemical variables, BMI, gender, and dialysis modality. In diabetics, the hazard ratio (HR) from Model 1 indicated no difference [1.046, 95% confidence limits (CL) 0.989-1.105; P> 0.1, HD was the reference] in mortality between PD and HD, while Model 2 demonstrated that PD patients had a 13.4% (1.134, CL 1.072-1.100, P < 0.0001) higher chance of death. In non-diabetics, hazard ratios (HRs) from Models 1 and 2 indicated that PD patients had a 23.5% (0.765, 0.722-0.812, P < 0.0001) and 11.9% (0.881, 0.30-0.935, P < 0.0001), respectively, lower likelihood of death than HD patients. CONCLUSION: Our study indicates that the results changed depending on the analytical methods used. We recommend that, due to the unequally distributed clinical conditions of patients at initiation, comparisons of mortality outcomes between dialysis modalities should be made with caution.

Age Distribution↗

PubMed2002

United States Renal Data System assessment of the impact of the National Kidney Foundation-Dialysis Outcomes Quality Initiative guidelines.

Since 1989, significant efforts have focused on improving the care of dialysis patients in the United States. Numerous organizations have developed clinical practice guidelines; however, few guidelines have received the broad support given to the National Kidney Foundation-Dialysis Outcomes Quality Initiative (DOQI). These guidelines, independently developed from an extensive review of the literature, include sections on dialysis adequacy, anemia treatment, and vascular access. To assess the impact of these guidelines on clinical practice, we evaluated data on hematocrits, recombinant human erythropoietin dosing, hemodialysis adequacy, and simple fistula and dialysis catheter utilization using Medicare dialysis provider claims and Medicare Part B physician services. Hematocrits have increased steadily, with the exception of the period when the Hematocrit Measurement Audit was in effect. After cancellation of the policy, hematocrits increased to the midpoint of the DOQI target range (34.4%). Although the level of dialysis therapy has stabilized, with the average urea reduction rate of 68% to 69.9% in 1997 to 1999 being slightly greater than the DOQI target of 65% or greater, geographic variability is apparent. Simple fistula placement rates increased by 45% during the pre-DOQI and post-DOQI period from 1994 to 1999. The use of temporary catheters decreased, whereas placement of permanent catheters has increased, which may reflect recommended practice guidelines. Although it appears that clinical practice guidelines have improved the clinical care of dialysis patients, considerable regional variations in care across the country should be given significant attention.

Anemia↗

PubMedDate not supplied

Comparison and survival of hemodialysis and peritoneal dialysis in the elderly.

Comparisons of clinical outcomes in hemodialysis (HD) and peritoneal dialysis (PD) patients have been marked by inconsistent results depending on the population studied and the methods used. In order to address this limitation of previous U.S. studies and to more specifically evaluate the higher-risk elderly population, we undertook a study of Medicare patients > or =67 years of age and assessed the comorbidity before they entered end-stage renal disease (ESRD) treatment. We then evaluated their survival outcomes at 6 month intervals in the follow-up period. In order to adequately assess the comorbidity we employed the Charlson comorbidity index and applied it to the comorbidity of the ESRD population up to 2 years before ESRD to characterize conditions from the start of ESRD treatment. We also counted inpatient hospital days in the 2 years prior to initiation of ESRD therapy as a marker of severity of disease. These two determinants of comorbidity were used to adjust the analysis along with other demographic and laboratory data. In the diabetic population, HD patients are shown to have a decreased risk of death, with the decrease ranging from 8% [relative risk (RR) (HD:PD) 0.82, 95% confidence interval (CI) 0.75-0.90] at month 6 to 54% [RR (HD:PD) 0.46, 95% CI 0.30-0.70] at month 48. In the nondiabetic population, HD patients are shown to have a 17% [RR (HD:PD) 1.17, 95% CI 1.07-1.28] increased risk of death in the first 6 months, and a decreased risk of death from months 6 to 48, a decrease ranging from 17% to 34%. Relative risks were significantly different from 1.0 at all intervals. These overall findings suggest that in the elderly population in the United States treated with PD had outcomes that were significantly worse than their HD patient counterparts, even after adjusting basic patient demographics, the comorbidity index, severity of disease with hospital days, demographics, and glomerular filtration rate (GFR) at the time of start of dialysis.

Aged↗

PubMedDate not supplied

Kidney Early Evaluation Program (KEEP). Findings from a community screening program.

PURPOSE: The Kidney Early Evaluation Program (KEEP), which was started in 1997, aims to identify persons at risk for chronic kidney disease (CKD) and encourage at-risk persons to seek evaluation and management from a healthcare provider. METHODS: Community screening was conducted using a standardized questionnaire and test panel that was administered by local affiliates of the National Kidney Foundation (NKF) using volunteer lay and medical personnel. The screening was limited to persons at high risk for CKD, which was defined as those with a personal history of diabetes or hypertension, or a first-order relative with diabetes, hypertension, or kidney disease. The KEEP Data Coordinating Center was established to maintain a de-identified database of demographic information and test results on the screened persons. RESULTS: Data on the first 11,246 participants were analyzed. As expected, the KEEP population was enriched with African Americans and was older than the general population. Diabetes was determined by self-report or abnormal blood glucose levels at screening and was present in 2690 of the persons screened. Chronic kidney disease was identified in 47.4% of this population. CONCLUSIONS: Targeted community screening for kidney disease in a high-risk population can identify a significant number of persons with CKD, enhance awareness of the disease, and may improve health-seeking behavior.

Chronic Disease↗