Donor-specific Factors Research Articles

Gene expression variation in the adult human retina

Despite evidence that differences in gene expression levels contribute significantly to phenotypic variation across individuals, there has been only limited effort to study gene expression variation in human tissue. To characterize expression variation in the normal human retina, the authors utilized a custom retinal microarray to analyze 33 normal retinas from 19 donors, aged 29 to 90 years. Statistical models were designed to separate and quantify biological and technical sources of variation, including age, gender, eye laterality, gene function, and age-by-gender interaction. Although the majority of the 9406 genes analyzed showed relatively stable expression across different donors (for an average gene the expression level value of 95 out of a 100 individual fell within a 1.23-fold range), 2.6% of genes showed significant donor-to-donor variation, with a false discovery rate of 10%. The mean expression ratio standard deviation was 0.15 ± 0.8, log2, with a range of 0.09 to 0.99. Genes selectively expressed in photoreceptors showed higher expression variation than other gene classes. Gender, age, and other donor-specific factors contributed significantly to the expression variation of multiple genes, and groups of genes with age- or gender-associated expression pattern were identified. These findings show that a significant fraction of gene expression variation in the normal human retina is attributable to identifiable biologic factors. The greater expression variability of many genes central to retinal function (including photoreceptor-specific gene) may be partially explained by the dynamics of the vision process, and raises the possibility that photoreceptor gene expression levels may contribute to phenotypic diversity across normal adult retinas. Additionally, as such diversity may result in different levels of disease susceptibility, exploring its sources may provide insights into the pathogenesis of retinal disease.—Hans E. Grossniklaus Despite evidence that differences in gene expression levels contribute significantly to phenotypic variation across individuals, there has been only limited effort to study gene expression variation in human tissue. To characterize expression variation in the normal human retina, the authors utilized a custom retinal microarray to analyze 33 normal retinas from 19 donors, aged 29 to 90 years. Statistical models were designed to separate and quantify biological and technical sources of variation, including age, gender, eye laterality, gene function, and age-by-gender interaction. Although the majority of the 9406 genes analyzed showed relatively stable expression across different donors (for an average gene the expression level value of 95 out of a 100 individual fell within a 1.23-fold range), 2.6% of genes showed significant donor-to-donor variation, with a false discovery rate of 10%. The mean expression ratio standard deviation was 0.15 ± 0.8, log2, with a range of 0.09 to 0.99. Genes selectively expressed in photoreceptors showed higher expression variation than other gene classes. Gender, age, and other donor-specific factors contributed significantly to the expression variation of multiple genes, and groups of genes with age- or gender-associated expression pattern were identified. These findings show that a significant fraction of gene expression variation in the normal human retina is attributable to identifiable biologic factors. The greater expression variability of many genes central to retinal function (including photoreceptor-specific gene) may be partially explained by the dynamics of the vision process, and raises the possibility that photoreceptor gene expression levels may contribute to phenotypic diversity across normal adult retinas. Additionally, as such diversity may result in different levels of disease susceptibility, exploring its sources may provide insights into the pathogenesis of retinal disease.—Hans E. Grossniklaus

CADAVER DONORS GREATER THAN AGE 55: WHICH KIDNEYS TO USE?

331 Many studies have demonstrated a significant detriment to long-term graft function with the use of older cadaver kidneys; yet the growing organ shortage has led to a steady increase in the use of older donors. The aim of our study was to evaluate the prognosis and outcome with older cadaver kidneys and to determine donor specific risk factors for poor outcome. Between 01/01/84 and 06/30/97, we did 709 primary cadaver kidney transplants: 107 with cadaver donors >55 years, and 602 with donors 18 to 55 years. The mean donor age in the group >55 was 61.2; in the group 18 to 55, 33.8 years (p=.001). Kidneys from older donors tended to be transplanted into older recipients (p=0.03). Graft survival was significantly worse with donors >55, but only in the subgroup of donors who died of cardiovascular or cerebrovascular causes. Recipients with donors >55 had a higher incidence of acute rejection (p=0.006), chronic rejection (p=0.001), and delayed graft function (p=0.001). By mutivariate analysis, cause of donor death was the most significant donor variable for poor outcome. Elevated donor creatinine (Cr) and prolonged kidney preservation time also tended toward increased risk. (Tables)TableTableConclusion: Older cadaver kidneys are now used more frequently, but they are associated with an increased incidence of delayed graft function and acute rejection and with decreased long-term graft survival. In our study, cerebrovascular or cardiovascular causes of donor death, elevated donor Cr, and prolonged kidney preservation time were associated with poor outcome. Knowing the risk factors may help decide which older cadaver kidneys to use.

Donor des-gamma-carboxy prothrombin positivity is a risk factor for poor early graft function in liver transplantation.

Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin that lacks coagulating activity. The aim of this study was to determine if the presence of DCP in the donor could be used as a marker of post-transplant graft function. We collected data and serum samples on 90 organ donors. DCP level was correlated with donor-specific factors and with graft function intraoperatively and in the early post-transplant period. Twenty-seven donors (30.0%) had positive DCP levels before harvesting. Although recipients were similar in demographics, preoperative liver function, and primary disease distribution, patients transplanted with livers from DCP-positive donors needed significantly more intraoperative transfusion. Furthermore, donor DCP positivity was identified as a preoperative risk factor for poor early graft function based on multivariate analysis (odds ratio = 6.58, P = 0.0032). Our findings suggest that DCP is another valuable marker for evaluating the quality of donor livers.

Donor des-gamma-carboxy prothrombin positivity is a risk factor for poor early graft function in liver transplantation

Abstract Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin that lacks coagulating activity. The aim of this study was to determine if the presence of DCP in the donor could be used as a marker of post-transplant graft function. We collected data and serum samples on 90 organ donors. DCP level was correlated with donor-specific factors and with graft function intraoperatively and in the early post-transplant period. Twenty-seven donors (30.0%) had positive DCP levels before harvesting. Although recipients were similar in demographics, preoperative liver function, and primary disease distribution, patients transplanted with livers from DCP- positive donors needed significantly more intraoperative transfusion. Furthermore, donor DCP positivity was identified as a preoperative risk factor for poor early graft function based on multivariate analysis (odds ratio = 6.58, P= 0.0032). Our findings suggest that DCP is another valuable marker for evaluating the quality of donor livers.

Quantitative liver function tests and donor-specific factors in the prediction of early outcome after liver transplantation

Quantitative liver function tests and donor-specific factors in the prediction of early outcome after liver transplantation

Chloride uptake into cultured airway epithelial cells from cystic fibrosis patients and normal individuals.

The chloride permeability of airway and sweat ductal epithelium of cystic fibrosis (CF) patients is decreased. This abnormality could represent an intrinsic characteristic of the epithelial cell or the response to a tonic extrinsic stimulus, in vivo. We cultured airway epithelial cells derived from CF and non-CF individuals under identical conditions that were free from donor-specific factors. Differences in the characteristics of cells that multiplied under these circumstances are unlikely to reflect the effects of extrinsic modulation present in the host. After 8-12 days in culture, the cells of CF and non-CF patients were similar in morphology and intracellular electrolyte content, but the CF cultures took up chloride at a reduced rate. The difference could not be attributed to a higher intracellular potential in CF cells or to the presence of a stilbene anion-sensitive chloride-chloride exchange in non-CF cells. We conclude that epithelial cells from CF patients grown in the absence of extracellular factors of the host express reduced cellular chloride permeability, a defect similar to that found in vivo and in freshly excised nasal epithelium.