Biomedical subjects

Edgar Milford

Publications and source records attributed to Edgar Milford.

7 recordsLinked to original sources

PubMed2005

Signaling T-cell survival and death by IL-2 and IL-15.

Interleukin 2 (IL-2) and interleukin 15 (IL-15) bind to common T-cell surface receptors comprised of unique alpha (IL-2R alpha or IL-15R alpha) and shared beta/gamma chain subunits. Ligation of this receptor by IL-2 can lead to apoptosis whereas IL-15 ligation favors cell survival. Our study examined intra-cellular signaling events associated with IL-2- and IL-15-induced apoptosis and survival in human T cells. We found IL-2 and IL-15 could both induce apoptosis and survival; the outcome depended on cytokine concentration. No qualitative differences in Jak/Stat, Ras/MAPK or PI3K/AKT signaling were seen over a wide range of IL-2 and IL-15 concentrations. These findings suggest that, like T-cell receptor signaling, IL-2R beta/gamma chain signaling is regulated, or "tuned," by the concentration of cytokine.

Apoptosis↗

PubMed2004

Assessment of optimal size and composition of the U.S. National Registry of hematopoietic stem cell donors.

BACKGROUND: The National Marrow Donor Program (NMDP) receives federal funding to operate a registry of over 4 million volunteer donors for patients in need of a hematopoietic stem cell transplant. Because minority patients are less likely to find a suitably matched donor than whites, special efforts have been aimed toward recruitment of minorities. Significant financial resources are required to recruit and tissue type additional volunteer donors. METHODS: Population genetics models have been constructed to project likelihoods of finding a human leukocyte antigen (HLA)-matched donor for patients of various racial/ethnic groups. These projections have been made under a variety of strategies for expansion of the NMDP Registry. Cost-effectiveness calculations incorporated donor unavailability and other barriers to transplantation. RESULTS: At current recruitment rates, the probability of an available HLA-A,B,DRB1 matched donor is projected to increase from 27% to 34%; 45% to 54%; 75% to 79%; and 48% to 55%, for blacks, Asians/Pacific Islanders, whites and Hispanics, respectively, by the year 2007. Substantial increases in minority recruitment would have only modest impacts on these projections. These projections are heavily affected by donor availability rates, which are less than 50% for minority volunteers. CONCLUSIONS: Continued recruitment of additional volunteers can improve the likelihood of finding an HLA-matched donor, but will still leave significant numbers of patients of all racial/ethnic groups without a match. Efforts to improve donor availability (especially among minorities) and to increase the number of patients with access to the NMDP Registry may prove to be more cost-effective means of increasing transplants.

Genetics, Population↗

PubMed2004

Dialysis dose and the effect of gender and body size on outcome in the HEMO Study.

BACKGROUND: Gender and body size have been associated with survival in hemodialysis populations. In recent observational studies, overall mortality was similar in men and women and higher in small patients. The effect of dialysis dose in each of these subgroups has not been tested in a clinical trial. METHODS: The HEMO Study was a controlled trial of dialysis dose and membrane flux in 1846 hemodialysis patients followed up for 6.6 years in 15 centers throughout the United States. We examined the effect of dialysis dose on mortality and on selected secondary outcomes in subgroups of patients. RESULTS: Adjusting for age only, overall mortality was lower in patients with higher body weight (P < 0.001), higher body mass index (P < 0.001), and higher body water content determined by the Watson formula (Vw) (P < 0.001), but was not associated with gender (P= 0.27). The RR of mortality comparing the high dose with the standard dose group was related to gender (P= 0.014). Women randomized to the high dose had a lower mortality rate than women randomized to the standard dose (RR = 0.81, P= 0.02), while men randomized to the high dose had a nonsignificant trend for a higher mortality rate than men randomized to the standard dose (RR = 1.16, P= 0.16). Analysis of both genders combined showed no overall dose effect (R = 0.96, P= 0.52), as reported previously. Vw was greater than 35 L in 84% of men compared with 17% of women. However, the RR of mortality for the high versus standard dose remained lower in women than in men after adjustment for the interaction of dose with Vw or with other size parameters, including weight and body mass index. Conversely, the dose effect was not significantly related to size parameters after controlling for the relationship of the dose comparison with gender. CONCLUSION: The data suggest that mortality and morbidity might be reduced by increasing the dialysis dose above the current standard in women but not in men. This effect was not explained by differences between men and women in age, race, or in several indices of body size. Because multiple comparisons were considered in this analysis, the role of gender on the effect of dialysis dose is suggestive and invites further study.

Black People↗

PubMed2004

Donor kidney exchanges.

Kidney transplantation from live donors achieves an excellent outcome regardless of human leukocyte antigen (HLA) mismatch. This development has expanded the opportunity of kidney transplantation from unrelated live donors. Nevertheless, the hazard of hyperacute rejection has usually precluded the transplantation of a kidney from a live donor to a potential recipient who is incompatible by ABO blood type or HLA antibody crossmatch reactivity. Region 1 of the United Network for Organ Sharing (UNOS) has devised an alternative system of kidney transplantation that would enable either a simultaneous exchange between live donors (a paired exchange), or a live donor/deceased donor exchange to incompatible recipients who are waiting on the list (a live donor/list exchange). This Regional system of exchange has derived the benefit of live donation, avoided the risk of ABO or crossmatch incompatibility, and yielded an additional donor source for patients awaiting a deceased donor kidney. Despite the initial disadvantage to the list of patients awaiting an O blood type kidney, as every paired exchange transplant removes a patient from the waiting list, it also avoids the incompatible recipient from eventually having to go on the list. Thus, this approach also increases access to deceased donor kidneys for the remaining candidates on the list.

Cadaver↗

PubMed2002

Effect of dialysis dose and membrane flux in maintenance hemodialysis.

BACKGROUND: The effects of the dose of dialysis and the level of flux of the dialyzer membrane on mortality and morbidity among patients undergoing maintenance hemodialysis are uncertain. METHODS: We undertook a randomized clinical trial in 1846 patients undergoing thrice-weekly dialysis, using a two-by-two factorial design to assign patients randomly to a standard or high dose of dialysis and to a low-flux or high-flux dialyzer. RESULTS: In the standard-dose group, the mean (+/-SD) urea-reduction ratio was 66.3+/-2.5 percent, the single-pool Kt/V was 1.32+/-0.09, and the equilibrated Kt/V was 1.16+/-0.08; in the high-dose group, the values were 75.2+/-2.5 percent, 1.71+/-0.11, and 1.53+/-0.09, respectively. Flux, estimated on the basis of beta2-microglobulin clearance, was 3+/-7 ml per minute in the low-flux group and 34+/-11 ml per minute in the high-flux group. The primary outcome, death from any cause, was not significantly influenced by the dose or flux assignment: the relative risk of death in the high-dose group as compared with the standard-dose group was 0.96 (95 percent confidence interval, 0.84 to 1.10; P=0.53), and the relative risk of death in the high-flux group as compared with the low-flux group was 0.92 (95 percent confidence interval, 0.81 to 1.05; P=0.23). The main secondary outcomes (first hospitalization for cardiac causes or death from any cause, first hospitalization for infection or death from any cause, first 15 percent decrease in the serum albumin level or death from any cause, and all hospitalizations not related to vascular access) also did not differ significantly between either the dose groups or the flux groups. Possible benefits of the dose or flux interventions were suggested in two of seven prespecified subgroups of patients. CONCLUSIONS: Patients undergoing hemodialysis thrice weekly appear to have no major benefit from a higher dialysis dose than that recommended by current U.S. guidelines or from the use of a high-flux membrane.

Adult↗

PubMed2002

Soluble HLA in saliva of patients with autoimmune rheumatic diseases.

OBJECTIVES: The limited number of studies addressing the presence of soluble human leukocyte antigen (HLA) in body fluids such as tears, urine, sweat, and saliva are restricted to healthy subjects. In this study, we applied solid-phase enzyme-linked immunoassay to quantify soluble HLA class I (sHLA-I) and class II (sHLA-II) molecules in saliva and in selected serum samples obtained from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS). RESULTS: While saliva from normal subjects (n=35) contained levels of sHLA-I that were undetectable (n=7) or ranged from 9 ng/ml to 70 ng/ml (30+/-3.7 ng/ml, n=28), sHLA-I among 38 patients with moderately active RA ( n=24) or SLE (n=14) were significantly elevated (222+/-81.4 ng/ml and 120+/-27.3 ng/ml, respectively, P<0.0001). Intriguingly, sHLA-I levels were even higher in patients whose disease was regarded as active. Specifically, sHLA-I averaged 683+/-189 ng/ml in patients with active RA (n=13) and 230+/-24.5 ng/ml in patients with active SLE (n=7). This was significantly higher than in patients with milder forms of these diseases (P<0.0001). All five subjects with SS had severe disease with high levels of sHLA-I (mean 486+/-86 ng/ml). The concentrations of saliva sHLA-II in the disease groups studied were comparable with levels found in normal controls. The sHLA-I in severe and mild states was investigated in purified serum and saliva from a patient with SS. While 44-kDa fragments of serum HLA-I were detectable in severe SS, they were undetectable in saliva HLA at any time; 35-37-kDa fragments of serum or saliva HLA-I were detected during both mild and severe disease. Interestingly, the 39-kDa fragment was detected in both body fluids during severe but not mild forms of SS. Similarly, the isoforms with the molecular masses 39 kDa and 44 kDa were mainly identified in the purified material obtained from serum of SLE patients. CONCLUSIONS: Collectively, our data suggest that the measurement of soluble HLA in body fluids can be of both diagnostic and prognostic value in the assessment of patients with autoimmune rheumatic disorders. The mechanism by which sHLA enters saliva is unclear, but they probably are not acquired from serum.

Adult↗

PubMed2002

Using a neural network with flow cytometry histograms to recognize cell surface protein binding patterns.

Flow cytometric systems are being used increasingly in all branches of biological science including medicine. To develop analytic tools for identifying unknown molecules such as the antibodies that recognize different structure in the identical antigens, we explored use of a neural network in flow cytometry data comparison. Peak locations were extracted from flow cytometry histograms and we used the Marquardt backpropagation neural networks to recognize identical or similar binding patterns between antibodies and antigens based on the peak locations. The neural network showed 93.8% to 99.6% correct classification rates for identical or similar molecules. This suggests that the neural network technique can be useful in flow cytometry histogram data analysis.

Antibodies, Monoclonal↗