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J W Young

Publications and source records attributed to J W Young.

At least 19 recordsLinked to original sources
PubMed2001

Identification of poor prognostic features among patients requiring mechanical ventilation after hematopoietic stem cell transplantation.

Patients who develop respiratory failure requiring mechanical ventilation after hematopoietic stem cell transplantation (HSCT) have very high mortality. Several investigators have identified prognostic features that can be used to identify a subset of these patients who are virtually certain to die, yet these have never been prospectively assessed. The objectives of this study were to determine the accuracy of published prognostic features for mortality and to determine the survival of patients who recover from respiratory failure. A systematic review of the literature was undertaken to identify reported poor prognostic features and survival rates. The study validated the reported poor prognostic features on a prospective, multicenter inception cohort of 226 patients with respiratory failure requiring mechanical ventilation after HSCT. The main outcome measures were determination of a baseline probability of death, drawn from literature review; likelihood ratio of mortality for each prognostic feature determined from the validation cohort; conditional probability of death in the presence of each feature; and 6-month survival of those who recover. Patients requiring mechanical ventilation after HSCT have a baseline probability of death of 82% to 96%. In the setting of combined hepatic and renal dysfunction, the probability of death rises to 98% to 100%. Other previously reported prognostic features are less strongly associated with mortality. For patients who recover from respiratory failure, the proportion surviving 6 months or longer ranges from 27% to 88%. It was concluded that in patients requiring mechanical ventilation after HSCT, the presence of combined hepatic and renal dysfunction is highly predictive of death. The presence of this feature may justify the recommendation to withdraw life-sustaining measures.

Adult↗
PubMed2000

Retrovirally transduced mouse dendritic cells require CD4+ T cell help to elicit antitumor immunity: implications for the clinical use of dendritic cells.

Presentation of MHC class I-restricted peptides by dendritic cells (DCs) can elicit vigorous antigen-specific CTL responses in vivo. It is well established, however, that T cell help can augment CTL function, raising the question of how best to present tumor-associated MHC class I epitopes to induce effective tumor immunity. To this end, we have examined the role of MHC class II peptide-complexes present on the immunizing DCs in a murine melanoma model. To present MHC class I- and II-restricted Ags reliably on the same cell, we retrovirally transduced bone marrow-derived DCs with the model Ag OVA encoding well-defined class I- and II-restricted epitopes. The importance of CD4+ T cells activated by the immunizing DCs in this model is demonstrated by the following findings: 1) transduced DCs presenting class I and class II epitopes are more efficient than class I peptide-pulsed DCs; 2) MHC class II-deficient DCs fail to induce tumor protection; 3) CD4+ T cell depletion abolishes induction of tumor protection; and 4) DCs presenting bovine serum Ags are more effective in establishing tumor immunity than DCs cultured in syngeneic serum. When MHC class II-deficient DCs were directly activated via their CD40 receptor, we indeed observed a moderate elevation of OVA-specific CTL activity. However, this increase in CTL activity was not sufficient to induce in vivo tumor rejection. Thus, our results demonstrate the potency of genetically modified DCs that express both MHC class I and II epitopes, but caution against the use of DCs presenting only the former.

Animals↗
PubMed2000

Circulating human B cells that express surrogate light chains and edited receptors.

Immunoglobulin gene recombination can result in the assembly of self-reactive antibodies. Deletion, anergy or receptor editing normally silence B cells that produce these autoantibodies. Receptor editing is highly efficient in mouse B cells that carry pre-recombined autoantibody transgenes or gene "knock-ins". However, it has been difficult to identify cells that have edited receptors in unmanipulated mice and humans. To try to identify such cells we isolated and characterized B cells that coexpress surrogate and conventional light chains (V-preB+L+) from the blood of normal human donors. V-preB+L+ B cells express RAG mRNA, display an unusual heavy and light chain antibody repertoire consistent with antiself reactivity, and show evidence of receptor editing. These cells accumulate in the joints of patients with rheumatoid arthritis, consistent with a role for V-preB+L+ B cells and receptor editing in autoimmune disease.

Agammaglobulinemia↗
PubMed2000

Virtual endoscopy--comparison with colonoscopy in the detection of space-occupying lesions of the colon.

BACKGROUND AND STUDY AIMS: A new technique has been described which combines abdominal helical computed tomography (CT) scanning and virtual reality computer technology, known as virtual colonoscopy (VC); the reconstructed images provide a simulation of the interior of the colon as viewed by endoscopy. We compared VC with conventional colonoscopy in patients with suspected or known colonic neoplasia. PATIENTS AND METHODS: A total of 38 patients, in whom there was a high likelihood of colonic polyps or cancer, underwent a noncontrast helical CT scan of the abdomen and pelvis after regular colonoscopy bowel preparation. The images were reconstructed into a VC presentation and compared with the subsequent conventional colonoscopy in a blinded manner. RESULTS: Conventional colonoscopy identified a total of 24 polyps 5 mm or greater. VC correctly identified five of 13 polyps 5-9 mm in size, and ten of 11 lesions greater than or equal to 10 mm in diameter. The reasons for four missed lesions were identified as being secondary to a collapsed rectum in two patients and stool in the right colon in two patients. The sensitivity and specificity per patient of VC for lesions greater than or equal to 5 mm were 66.7% and 75.0% respectively, and for lesions greater than 1 cm were 90.0% and 82.1%, respectively. CONCLUSIONS: Virtual colonoscopy is feasible, well tolerated, and capable of detecting most lesions greater than 10 mm in diameter. This technique is continuing to be developed and warrants further evaluation as a diagnostic and screening tool in colorectal neoplasia.

Adult↗
PubMed2000

Enzyme, bacterial inoculant, and formic acid effects on silage composition of orchardgrass and alfalfa.

We evaluated the effects of cellulase (from Trichoderma longibrachiatum) application rates on neutral detergent fiber (NDF) concentration and fermentation products of orchardgrass (Dactylis glomerata L.) and alfalfa (Medicago sativa L.) silages harvested with decreasing dry matter (DM) digestibility. Additionally, the impacts of inoculant (Lactobacillus plantarum and Pediococcus cerevisiae), pectinase (from Aspergillus niger), or formic acid on silage composition were studied. Forages wilted to a DM content of about 320 g/kg were ensiled in laboratory silos for 60 d. Cellulase, combined with inoculant, was applied at 2, 10, and 20 ml/kg of herbage (at least 2500 IU/ml). Cellulase at 10 ml/kg was also applied alone or in combination with pectinase and inoculant or formic acid. The NDF concentration of orchardgrass silage decreased with increasing cellulase up to 20 ml/kg, at which NDF content was decreased by 30%. The NDF concentration of alfalfa silage decreased with increasing cellulase application up to 10 ml/kg, at which NDF content was decreased by 13%. Immature plants were more responsive to cellulase treatment than mature plants. Cellulase at 2 ml/kg combined with inoculant improved fermentation characteristics of the silages but generally, there was no effect on silage fermentation by higher cellulase applications, resulting in an accumulation of sugar. The improved fermentation of orchardgrass treated with cellulase and inoculant was mostly related to the effect of inoculant, whereas cellulase alone improved fermentation characteristics of alfalfa silage and this effect was enhanced by addition of inoculant. Decreased NDF and increased sugar concentrations did not improve the in vitro DM digestibility of cellulase-treated silages.

Aspergillus niger↗
PubMed2000

Paucity of functional T-cell memory to melanoma antigens in healthy donors and melanoma patients.

The functional characteristics of CD8+ T cells specific for melanoma antigens (MAs) have often been defined after in vitro culture using nonprofessional antigen-presenting cells. We have examined CD8+ T-cell immunity to MAs and a viral antigen (influenza) in uncultured T cells of healthy donors and melanoma patients using autologous, mature, monocyte-derived dendritic cells (DCs) pulsed with peptide antigens and viral vectors. Antigen-specific IFN-gamma-producing T cells reactive with HLA-A*0201-restricted peptides from four melanoma antigens (MelanA/MART-1, MAGE-3, tyrosinase, and gp100) were detected only at low frequencies (<30 per 2 x 10(5) peripheral blood mononuclear cells for each of the MAs) from HLA-A2.1-positive healthy donors (n = 12) and patients with stages III/IV melanoma (n = 8). Detection of MA-specific, but not influenza matrix peptide (Flu-MP)-specific, T cells required a high concentration (10 microg/ml) of the peptide in this assay. Furthermore, these T cells did not recognize endogenously processed antigen on tumor cell lines or cells infected with viral vectors capable of expressing MAs. The use of autologous, mature DCs led to a significant increase in the number of Flu-MP, but not MA-specific, T cells in 16-h ELISPOT assays for both melanoma patients and healthy donors. In 1-week cocultures with DCs pulsed with 10 microg/ml peptide, MelanA/MART-1-specific T cells did not readily proliferate or differentiate into lytic effectors, in contrast to strong influenza-specific lytic responses. Therefore, despite distinct memory responses to influenza antigens, melanoma patients and healthy controls have a paucity of MA-reactive memory T cells, failing to rapidly generate IFN-gamma-secreting lytic effectors in short-term assays, even when stimulated by DCs.

Antigens↗
PubMed1999

Comparison of immune reconstitution after unrelated and related T-cell-depleted bone marrow transplantation: effect of patient age and donor leukocyte infusions.

Unrelated bone marrow transplantation (BMT) is often complicated by fatal opportunistic infections. To evaluate features unique to immune reconstitution after unrelated BMT, the lymphoid phenotype, in vitro function, and life-threatening opportunistic infections after unrelated and related T-cell-depleted (TCD) BMT were analyzed longitudinally and compared. The effects of posttransplant donor leukocyte infusions to treat or prevent cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infections on immune reconstitution were also analyzed. This study demonstrates that adult recipients of TCD unrelated BMTs experience prolonged and profound deficiencies of CD3(+), CD4(+), and CD8(+) T-cell populations when compared with pediatric recipients of unrelated BMT and adults after related BMT (P <.01), that these adults have a significantly increased risk of life-threatening opportunistic infections, and that the rate of recovery of CD4 T cells correlates with the risk of developing these infections. Recovery of normal numbers of CD3(+), CD8(+), and CD4(+) T-cell populations is similar in children after related or unrelated BMT. This study also demonstrates that adoptive immunotherapy with small numbers of unirradiated donor leukocytes can be associated with rapid restoration of CD3(+), CD4(+), and CD8(+) T-cell numbers, antigen-specific T-cell responses, and resolution of CMV- and EBV-associated disease after unrelated TCD BMT.

Adolescent↗
PubMed1999

Dendritic cells.

Explore the source record for details and available documents.

Animals↗
PubMed1999

Dendritic cells: expansion and differentiation with hematopoietic growth factors.

Dendritic cells are critical initiators of immune responses mediated by T and B lymphocytes. Dendritic cells process antigens captured in the periphery, then emigrate to lymphoid organs. There they complete their maturation by upregulating important accessory molecules and secreting cytokines, all of which support potent stimulation of antigen-specific lymphocytes. These lymphocytes return to the periphery to complete the immune response. Investigators have discovered culture systems that use exogenous hematopoietic cytokines to support the growth, differentiation, and maturation of dendritic cells in larger numbers and greater purity than was ever before possible. This has rendered dendritic cells accessible to detailed experimental evaluations and clinical applications. Dendritic cells provide a powerful means of controlling both normal and pathologic immunity.

Cell Differentiation↗
PubMed1999

Metabolic responses of lactating dairy cows to 14-day intravenous infusions of glucagon.

Twenty cows were assigned at parturition to two groups to study metabolic effects of continuous intravenous infusions of glucagon. Groups were control cows and cows treated with glucagon at 10 mg/d for 14 d starting at d 21 postpartum. Daily blood samples and nine liver biopsies were taken from d 7 to 49 postpartum. Plasma glucagon increased six- to seven-fold during infusions of treated cows. Plasma insulin was increased heterogeneously by glucagon infusions. Plasma glucose increased 11.5 and 9.0 mg/dl during wk 1 and 2 of glucagon infusions. No other plasma metabolites tested (nonesterified fatty acids, beta-hydroxybutyrate, and urea N) were affected by glucagon infusions. Liver glycogen decreased by d 2 of glucagon infusion but was repleted to preinfusion values by d 7 and increased to 169% of the preinfusion baseline values at 3 d after cessation of glucagon. Milk production decreased transiently during glucagon infusions. Both milk production and milk protein percentage decreased during glucagon infusion, which could imply a decreased availability of amino acids for milk protein synthesis. Feed intakes did not increase during glucagon infusions, which was in contrast to the control group. Results indicated that glucagon infusions caused liver glycogenolysis initially and probably enhanced gluconeogenesis but glucagon did not appear to increase lipolysis from adipose tissue in these early lactating dairy cows.

3-Hydroxybutyric Acid↗
PubMed1999

Metabolic responses of dairy cows and heifers to various intravenous dosages of glucagon.

To evaluate the ability of glucagon to improve carbohydrate status in dairy cows without an increase in blood lipids, glucagon was infused intravenously for 48 h into lactating cows and spayed heifers in three crossover experiments. During Experiment 1, glucagon (5 and 20 mg/d) was infused into four midlactation cows. Experiment 2 involved the infusion of 0, 2.5, 5.0, or 10 mg/d of glucagon into eight heifers; each heifer received two of the dosages. In Experiment 3, four early lactation cows were treated with 5 and 10 mg/d of glucagon. Glucagon consistently increased plasma glucose concentrations in a dose-dependent fashion throughout the 48-h periods. Plasma insulin was increased in a nondose-dependent manner by glucagon in Experiment 1. Plasma urea N was increased when glucagon was administered at 5 mg/d during Experiment 2 and tended to be decreased during Experiment 3. Nonesterified fatty acids in plasma were, in most cases, not affected; however, they were increased by glucagon at 10 mg/d during Experiment 2. Concentrations of beta-hydroxybutyrate were increased only by the 20-mg/d dosage. During Experiment 1, liver glycogen concentrations decreased by 2.1% (wet weight basis) for both dosages of glucagon, and concentrations of total lipid in the liver were increased by 0.6% (wet weight basis) by 20 mg/d of glucagon. Milk fat percentage was increased by glucagon, but milk volume and milk protein production were decreased during Experiment 1. Glucagon improved carbohydrate status over the 48-h periods in all experiments but did not increase plasma nonesterified fatty acids except at the 10-mg/d dosage in Experiment 2.

3-Hydroxybutyric Acid↗
PubMed1999

Alleviation of fatty liver in dairy cows with 14-day intravenous infusions of glucagon.

Twenty multiparous cows were fed additional concentrate during the final 30 d prepartum to cause susceptibility to fatty liver. From 14 to 42 d postpartum, all cows were subjected to a protocol to induce fatty liver and ketosis. To test glucagon as a treatment for fatty liver, either glucagon at 10 mg/d or excipient was infused via the jugular vein from 21 to 35 d postpartum. All cows had fatty liver at 14 d postpartum and became ketonemic and hypoglycemic during the induction of ketosis. Glucagon increased plasma glucose to 142% of that of controls throughout the 14-d treatment. The hypoinsulinemia present in cows with fatty liver was not affected by glucagon. Plasma beta-hydroxybutyrate and nonesterified fatty acids were decreased by glucagon. At 6 d postpartum, liver triacylglycerol averaged 12.9% of liver (wet weight basis). Glucagon had decreased triacylglycerol content of livers by 71% at d 35. Glycogen was 1.0% of the wet weight of livers at 6 d in milk, but it was decreased by glucagon to 0.5% at 2 d after glucagon began. Glycogen then increased in cows treated with glucagon until at 38 d in milk liver glycogen was 3.7% versus 1.6% in controls. Our results document that glucagon decreases the degree of fatty liver in early lactation dairy cows, which also decreases the incidence of ketosis after alleviation of fatty liver.

3-Hydroxybutyric Acid↗
PubMed1999

Regulation of messenger ribonucleic acid expression for gluconeogenic enzymes during glucagon infusions into lactating cows.

The effects of glucagon infusions on expression of mRNA for enzymes that regulate gluconeogenesis were studied in lactating cows. Normal cows and cows with fatty liver that were susceptible to ketosis were assigned to either glucagon-treated or control groups. Glucagon at 0 or 10 mg/d was infused for 14 d beginning at d 21 postpartum. In normal cows, glucagon infusions increased concentrations of both plasma glucagon and glucose, which caused plasma insulin to increase. Consequently, hepatic phosphoenolpyruvate carboxykinase mRNA decreased during wk 1 of glucagon infusions. Glucagon infusions into cows with fatty liver also increased plasma glucagon and glucose, but concentrations of plasma insulin and hepatic phosphoenolpyruvate carboxykinase mRNA did not change. More phosphoenolpyruvate carboxykinase mRNA was present in the livers of cows with fatty liver than in livers of normal cows. In a follow-up experiment with midlactation cows, 3.5-h infusions of glucagon at 14 mg/d increased plasma glucose and insulin and decreased plasma nonesterified fatty acids and hepatic glycogen. Hepatic phosphoenolpyruvate carboxykinase mRNA was decreased 41%, pyruvate carboxylase mRNA was increased 50%, but fructose-1,6-bisphosphatase mRNA did not change. We conclude that the expression of the hepatic phosphoenolpyruvate carboxykinase gene in normal cows is inhibited by insulin to balance elevated carbohydrate status during glucagon infusions; however, inhibited expression of hepatic phosphoenolpyruvate carboxykinase mRNA probably is not involved in the pathogenesis of lactation ketosis.

3-Hydroxybutyric Acid↗
PubMed1998

T-cell-depleted allogeneic bone marrow transplantation as postremission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease.

Thirty-one consecutive patients with acute myelogenous leukemia (AML) in first complete remission and 8 with AML in second complete remission received T cell-depleted allogeneic bone marrow transplants from HLA-identical sibling donors. Patients received myeloablative cytoreduction consisting of hyperfractionated total body irradiation, thiotepa, and cyclophosphamide. Those patients at risk for immune-mediated graft rejection received additional immune suppression with antithymocyte globulin and methylprednisolone in the early peritransplant period. Patients with AML who underwent allogeneic T-cell-depleted bone marrow transplantations (BMT) in first or second remission have achieved respective disease-free survival (DFS) probabilities of 77% (median follow-up at approximately 56 months) and 50% (median follow-up at approximately 48 months). Ten of 31 patients transplanted in first remission were > or = 40 years old and have attained a DFS at 4 years of 70%. For patients with AML transplanted in first or second remission, the respective cause-specific probabilities of relapse were 3.2% or 12.5%, and those of nonleukemic mortality were 19.4% or 37.5%. There were no cases of immune-mediated graft rejection and no cases of grade II to IV acute graft-versus-host disease (GVHD). All survivors enjoy Karnofsky performance scores (KPS) of 100%, except 2 patients with KPS of 80% to 90%. T-cell-depleted allogeneic BMT can provide durable DFS together with an excellent performance status in the majority of patients with de novo AML. In addition, GVHD is not an obligatory correlate of the graft-versus-leukemia benefit or freedom from relapse afforded by allogeneic BMT administered as postremission therapy for AML. This study provides a basis for prospective comparison with other postremission therapies considered standard in the management of patients with this disease.

Adolescent↗
PubMed1998

Local staging of esophageal cancer using endoscopic magnetic resonance imaging: prospective comparison with endoscopic ultrasound.

BACKGROUND AND STUDY AIMS: The magnetic resonance endoscope consists of a non-ferrous endoscope with a radiofrequency receiver coil incorporated into its tip. The aim of this study was to assess the accuracy of endoscopic magnetic resonance imaging for the local staging of esophageal cancer. PATIENTS AND METHODS: Prospectively, 15 patients with biopsy-proven cancer of the esophagus (n = 9) or gastroesophageal junction (n = 6) underwent endosonography followed by imaging by the magnetic resonance endoscope. The results of endoscopic magnetic resonance imaging were assessed blindly, then compared with those of endosonography, which served as the gold standard. RESULTS: Endoscopic magnetic resonance imaging of transmural tumor invasion agreed with ultrasonography in 11/15 cases and of nodal state in 12/15 cases. Endoscopic magnetic resonance images were inadequate in four cases as a result of motion artifacts. CONCLUSIONS: Endoscopic magnetic resonance imaging of esophageal cancer diagnoses local staging that is comparable to endosonography. In future, the combination of endoscopic and conventional magnetic resonance scanning may provide comprehensive staging of esophageal cancer.

Adenocarcinoma↗