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Biomedical subjects

J W Young

Publications and source records attributed to J W Young.

At least 19 recordsLinked to original sources
PubMed1992

T-cell-depleted allogeneic bone marrow transplantation in adults with acute nonlymphocytic leukemia in first remission.

We prospectively evaluated the efficacy of T-cell-depleted bone marrow transplantation (BMT) in adults with de novo acute nonlymphocytic leukemia (ANLL) in first complete remission (CR), with regard to relapse-free survival and incidence of graft-versus-host disease (GvHD). Thirty-one patients older than 16 years (range, 16.5 to 43.2) received T-cell-depleted grafts for this purpose from related HLA/MLC-compatible donors. Twelve of the patients were older than 30 years at the time of transplantation. Patients were prepared with hyperfractionated total body irradiation (HFTBI; 1,375 to 1,500 cGy) and high-dose cyclophosphamide (120 mg/kg). T cells were removed from the marrow grafts by a two-step soybean lectin agglutination and sheep red blood cell (sRBC)-rosette procedure, achieving a 2.5- to 3-log depletion of clonable T lymphocytes. No additional prophylaxis against GvHD was administered. The median age at transplantation was 28.8 years; the median interval from diagnosis to transplantation was 3.8 months, and from CR was 2.7 months. Seventy-four percent received consolidation after remission induction therapy. The product-limit estimate of disease-free survival (DFS) at 3 years is 45% (95% confidence interval [CI], 24% to 66%), and the cause-specific probability of relapse is 13%. The median follow-up of the survivors is 72 months (range, 34.5 to 95.6). Median time to achieve a sustained absolute neutrophil count of 500 or greater was 16 days, and to maintain an untransfused platelet count of 20,000 or greater was 20 days. Five patients suffered immune-mediated graft rejection. Three patients developed grade I to II acute GvHD limited to the skin, which resolved promptly with brief courses of systemic steroids. None of the patients has developed clinically apparent chronic GvHD or a secondary lymphoproliferative disorder, and no patient is receiving immunosuppressive therapy. T-cell-depleted BMT by the method reported here is a favorable option as postremission therapy for adults with de novo ANLL in first remission who have an HLA/MLC-compatible related donor, and it is not associated with an increased risk of relapse posttransplant.

Adolescent↗
PubMed1992

Double injuries of the forearm: a common occurrence.

To evaluate the frequency of different types of forearm fractures and, in particular, determine the frequency of double injury to the forearm, the authors prospectively examined 119 consecutive forearm fractures and found double injuries to the forearm in all but five cases. In 79 of the 119 patients (66%), ligamentous injury was seen in addition to the obvious fracture. Nine patients with apparent isolated fractures on initial radiographs underwent examination by means of radionuclide bone scanning, which revealed a second injury in eight of them. Four patients with apparent single fractures did not undergo bone scanning because of their critical conditions. In four patients, a single fracture was initially diagnosed, but after reduction and casting, dislocation of the radioulnar joint was seen. These findings indicate that injury to the forearm almost invariably occurs at two or more sites and involves either both bones or bone and ligament. Because the distal radioulnar joint was affected in 71 patients (60%), scrutiny of the wrist is imperative whenever injuries to the bones of the forearm are discovered.

Arthrography↗
PubMed1992

The B7/BB1 antigen provides one of several costimulatory signals for the activation of CD4+ T lymphocytes by human blood dendritic cells in vitro.

T cells respond to peptide antigen in association with MHC products on antigen-presenting cells (APCs). A number of accessory or costimulatory molecules have been identified that also contribute to T cell activation. Several of the known accessory molecules are expressed by freshly isolated dendritic cells, a distinctive leukocyte that is the most potent APC for the initiation of primary T cell responses. These include ICAM-1 (CD54), LFA-3 (CD58), and class I and II MHC products. Dendritic cells also constitutively express the accessory ligand for CD28, B7/BB1, which has not been previously identified on circulating leukocytes freshly isolated from peripheral blood. Dendritic cell expression of both B7/BB1 and ICAM-1 (CD54) increases after binding to allogeneic T cells. Individual mAbs against several of the respective accessory T cell receptors, e.g., anti-CD2, anti-CD4, anti-CD11a, and anti-CD28, inhibit T cell proliferation in the dendritic cell-stimulated allogeneic mixed leukocyte reaction (MLR) by 40-70%. Combinations of these mAbs are synergistic in achieving near total inhibition. Other T cell-reactive mAbs, e.g., anti-CD5 and anti-CD45, are not inhibitory. Lymphokine secretion and blast transformation are similarly reduced when active accessory ligand-receptor interactions are blocked in the dendritic cell-stimulated allogeneic MLR. Dendritic cells are unusual in their comparably higher expression of accessory ligands, among which B7/BB1 can now be included. These are pertinent to the efficiency with which dendritic cells in small numbers elicit strong primary T cell proliferative and effector responses.

Antigen-Presenting Cells↗
PubMed1992

Diagnosis of pelvic fractures in patients with acute pelvic trauma: efficacy of plain radiographs.

Although CT is widely recognized as an important adjunct to plain films in the evaluation of patients with acute pelvic trauma, accurate diagnosis of orthopedic injuries with plain films alone is often important to determine if immediate external fixation is necessary. The purpose of this study was to determine the efficacy of plain radiographs in the detection of pelvic fractures and dislocations in patients with acute pelvic trauma by using CT as the gold standard. CT scans and plain films collected prospectively in 50 patients with acute pelvic injuries were evaluated independently, and fractures and dislocations were identified and tabulated. Of a total of 162 fractures and dislocations seen on CT, only 14 (9%) were misdiagnosed on plain films. None of these misdiagnoses altered patients' management. Sixteen (80%) of 20 cases of intraarticular fragments in the hip joint associated with acetabular fractures were not identified on plain films. We conclude that plain film examination of the patient with pelvic trauma is sufficient to identify virtually all clinically important fractures and dislocations. Plain radiographs alone are not accurate in detecting fracture fragments within the hip joint.

Acetabulum↗
PubMed1992

Effects of ketones, acetate, and glucose on in vitro immunoglobulin secretion by bovine lymphocytes.

Individual and combined effects of ketones, acetate, and glucose on IgM secretion by bovine blood lymphocytes were evaluated in vitro. Supernatants from 14-d cultures of unstimulated and mitogen- or antigen-stimulated mono-nuclear leukocytes were harvested and analyzed for total and antigen-specific IgM. Ketones, acetate, and 1,3-butanediol individually added up to 6.25 mM had no effect on total IgM secreted by cells grown in medium containing 11.1 mM glucose. However, butyrate at 6.25 mM inhibited IgM secretion. Addition of a mixture of ketones approximating plasma levels of severely ketotic cows inhibited mitogen-induced IgM secretion in 11.1 mM glucose-supplemented cultures. Results from experiments evaluating effects of glucose concentrations on IgM secretion indicated that plasma glucose concentration associated with the ketotic state (1.66 mM), compared with normal plasma glucose concentration (3.33 mM), did not affect total or antigen-specific IgM secretion. Supplementation of cultures containing up to 3.33 mM glucose with ketones, acetate, or both either had no effect or a modest stimulatory effect. These data indicate that effects of ketones and acetate on IgM secretion are dependent on the concentration of glucose in culture and suggest that changes in plasma glucose, ketone, and acetate concentrations associated with bovine ketosis do not alter IgM secretion in vivo.

Acetates↗
PubMed1992

Metabolic changes in dairy cows with ketonemia in response to feed restriction and dietary 1,3-butanediol.

The objective was to measure progressive changes in metabolism of cows during a protocol that induced subclinical ketosis. From d 14 to 42 postpartum, 13 Holstein cows were in either a control group (6 cows) or a ketosis induction group (7 cows) that was restricted to 80% of ad libitum intake and fed 1,3-butanediol (7% of DM). Six ketosis induction cows developed ketonemia but not clinical ketosis; cow 7 developed clinical ketosis. Milk production was less, but fat content was greater, for ketonemic cows. Energy balance reached a nadir of -7.2 Mcal/d at d 21 for ketonemic cows, whereas controls reached energy equilibrium at d 28. Concentrations of NEFA in plasma and of beta-hydroxybutyrate in whole blood increased during ketonemia. Dextran sulfate-precipitable cholesterol and triglyceride in serum were increased only at d 21 and not at d 28, 35, 42, or 49. Concentrations of glycogen, total lipid, triglyceride, and cholesterol in liver increased during ketonemia. Oxidation of palmitate to CO2 was greater at d 21 in liver slices from ketonemic cows, whereas oxidation to acid-soluble products remained constant for those cows but decreased for controls. The ketonemic cows had lower weight ratios of triglyceride to glycogen in liver during pretreatment than those that became clinically ketotic in earlier studies (.5 vs. greater than or equal to 1.8). Susceptibility to clinical ketosis, therefore, may be indicated by increased hepatic triglyceride to glycogen ratios during the peripartal period.

3-Hydroxybutyric Acid↗
PubMed1991

Case report 660: Adamantinoma of tibia.

An adamantinoma of the tibia is presented, for which the CT and MRI characteristics are described. Both imaging modalities were excellent in providing information as to the extent and invasiveness of the tumor, although MRI had the advantage of providing immediate high quality sagittal visualization. Comparison is made briefly between adamantinoma and both fibrous dysplasia and osteofibrous dysplasia.

Bone Neoplasms↗
PubMed1991

Signals arising from antigen-presenting cells.

It has been customary to consider that antigen-presenting cells provide, in addition to the presented antigen, a second or co-stimulatory signal that leads to T-cell growth and effector function. The recent literature indicates that this two-signal notion oversimplifies the function of antigen-presenting cells. Instead it is useful to consider four groups of events: the formation of peptide-MHC complexes, the role of soluble cytokines, the action of antigen-presenting cell-T cell molecular couples distinct from the receptor for peptide MHC, and the function of antigen-presenting cells in situ.

Animals↗
PubMed1991

Hemorrhage associated with pelvic fractures: causes, diagnosis, and emergent management.

The high risk of exsanguinating hemorrhage in patients with pelvic ring disruption demands aggressive, yet balanced orthopedic and angiographic management as soon as patients are admitted to the emergency department. We present a perspective of our experience in two trauma centers and propose a logical approach to early prediction, diagnosis, and management of hemorrhage associated with pelvic fractures. Our method is based on knowledge of pelvic anatomy and an understanding of the mechanisms of injury and their wounding capacity, given that the mechanism of injury determines the type of pelvic ring disruption and that the probability of arterial hemorrhage is--to a great extent--a function of the type of pelvic fracture. The risks of diagnostic peritoneal lavage and of excessive radiologic studies of noncritical injuries are emphasized. The principles guiding arterial embolization and the application of external fixators are discussed.

Angiography↗
PubMed1991

Regulation of in vitro palmitate oxidation in liver from dairy cows during early lactation.

Regulatory effects of carnitine, glucose, some glucogenic compounds (propionate, pyruvate, alanine, lactate, glycerol, and fructose), ketone bodies (acetate, acetoacetate, and beta-hydroxybutyrate), and insulin on oxidation of palmitate were studied in slices of liver obtained from high producing dairy cows during early lactation. A total of 77 biopsies of liver from 21 multiparous Holstein cows (36 +/- 16 d postpartum) was used. L-Carnitine increased oxidation of palmitate to CO2 by more than twofold and oxidation to acid-soluble products by about fourfold. Propionate decreased oxidation of palmitate in liver slices incubated without added carnitine, but the decrease was lessened by carnitine. Pyruvate, lactate, and alanine increased palmitate oxidation, especially in the presence of carnitine. Glycerol, glucose, and insulin tended to decrease palmitate oxidation in the absence of carnitine. Fructose tended to decrease oxidation to CO2 but did not affect oxidation to acid-soluble products. Acetate and acetoacetate decreased oxidation of palmitate, whereas beta-hydroxybutyrate decreased palmitate oxidation in the absence of carnitine but increased palmitate oxidation in its presence. In general, carnitine decreased the inhibitory effects of compounds that decreased palmitate oxidation but increased the stimulatory effects of compounds that increased palmitate oxidation.

Alanine↗
PubMed1991

Effects of ketones, acetate, butyrate, and glucose on bovine lymphocyte proliferation.

Blood leukocytes from age-matched heifers were used to determine effects of ketones, acetate, butyrate, and glucose on in vitro lymphocyte proliferation. Lymphocytes stimulated with concanavalin A, phytohemagglutinin-P, or pokeweed mitogen were cultured in the presence or absence of beta-hydroxybutyrate, acetoacetate, acetone, acetate, butyrate, and glucose. Only supraphysiological levels of beta-hydroxybutyrate inhibited proliferation in cultures of mitogen-stimulated lymphocytes, whereas mixtures of beta-hydroxybutyrate and acetoacetate at levels seen in severe ketosis stimulated concanavalin A and phytohemagglutinin-P-driven proliferation. Because acetoacetate was a lithium salt, lithium chloride served as a negative control. Results suggest the enhanced proliferation by cultures containing lithium acetoacetate was due to lithium, not acetoacetate. Butyrate (at concentrations greater than seen in bovine plasma) and acetate at normal levels inhibited proliferation. Concanavalin A- and pokeweed-mitogen-driven proliferation was greater in cultures containing lower glucose levels, but acetate added to cultures containing low glucose inhibited concanavalin A-stimulated proliferation. Proliferation by pokeweed mitogen-stimulated cultures containing acetate, beta-hydroxybutyrate, and acetoacetate was suppressed at the lower concentrations of glucose tested. In conclusion, ketones, butyrate, and glucose at concentrations occurring in vivo had minimal effects on bovine lymphocyte proliferation in vitro. Levels of acetate associated with ketosis suppressed lymphocyte function and may alter immune responsiveness in vivo.

Acetates↗
PubMed1991

Regulation of in vitro metabolism of palmitate by carnitine and propionate in liver from dairy cows.

Regulation of in vitro palmitate metabolism by carnitine and propionate was investigated in liver obtained by biopsy from fasted nonlactating cows and from cows during early lactation. Liver slices from nonlactating cows during a 7-d fast esterified less palmitate than those from the same cows before fasting. Carnitine added in vitro increased hepatic oxidation and decreased esterification of palmitate in fed cows, but effects of carnitine were less during fasting. Propionate added in vitro decreased oxidation of palmitate; the effect was greater during fasting. In liver slices from cows during early lactation, carnitine increased oxidation and total utilization of palmitate and decreased palmitate esterification. Addition of tetradecylglycidic acid, an inhibitor of carnitine palmitoyltransferase I, prevented the carnitine-induced changes in palmitate metabolism. Substantial carnitine-independent oxidation of palmitate was observed in the presence of tetradecylglycidic acid. Tetradecylglycidic acid decreased esterification of palmitate to triglycerides but increased esterification to diglycerides. Effects of tetradecylglycidic acid and either propionate or pyruvate on palmitate oxidation were additive, indicating that propionate and pyruvate affect palmitate oxidation at sites other than carnitine palmitoyltransferase I. No interactions were detected between carnitine and propionate, but both compounds were potent regulators of palmitate metabolism in liver slices from cows during early lactation.

Animals↗
PubMed1991

Metabolic changes in blood and liver during development and early treatment of experimental fatty liver and ketosis in cows.

Eighteen cows were assigned in equal numbers to three groups: control, ketosis induction by using feed restriction plus dietary 1,3-butanediol to provide ketone bodies, and glucose treatment with 484 g/d of glucose infused intraduodenally starting 7 d after beginning ketosis induction. Ketosis induction, begun at d 15 postpartum, caused ketonemia and gradual development of clinical ketosis by d 40 to 45. None of the cows in the control or glucose-treated groups became ketotic. Concentrations of NEFA in plasma of cows that became ketotic increased 3.0-, 2.6-, and 1.9-fold at 3 wk before, 2 wk before, and at ketosis, respectively, but increased nonsignificantly for glucose-treated cows. Concurrently, beta-hydroxybutyrate increased 3.5-, 5.8- and 8.4-fold for cows that became ketotic but 1.6-fold or less for glucose-treated cows. Plasma acetate increased dramatically 2 wk before ketosis. Liver glycogen content decreased to nearly 0 by 2 wk before ketosis occurred, but it increased to prepartal values in glucose-treated cows. Liver triglycerides averaged 2.0% of wet weight at d 5 for all cows but increased to 8 to 10% for about 2 wk before ketosis occurred. Microscopy of liver samples demonstrated progressive accumulation of lipid globules, which began in hepatocytes near the central vein and progressed toward the portal triad. Visible lipid content reached a peak 2 wk before ketosis. Hepatic in vitro gluconeogenic capacity decreased significantly for ketosis induction protocol cows when clinical ketosis was detected. Results indicate that experimental ketosis was preceded by metabolic abnormalities up to 2 wk before clinical ketosis occurred. The key events for onset of clinical ketosis, however, were not elucidated.

3-Hydroxybutyric Acid↗
PubMed1991

Metabolic changes in blood and liver of dairy cows during either feed restriction or administration of 1,3-butanediol.

Previous research has shown that a combination of feed restriction and dietary 1,3-butanediol starting at 14 d post-partum resulted in fatty liver and ketosis. Sixteen multiparous Holstein cows were used to determine effects of feed restriction or 1,3-butanediol as separate treatments. Treatments during d 14 to 42 postpartum were 1) control (ad libitum intake), 2) 20% feed restriction, or 3) control plus dietary 1,3-butanediol (5.5% of DM). From d 43 to 56, cows assigned to treatments 2 and 3 received a combination of feed restriction and butanediol. One cow on treatment 2 developed ketosis, but not fatty liver, after only 4 d of feed restriction. No other cows developed fatty liver or ketosis. Both treatments decreased milk production compared with controls. Feed restriction increased the extent of negative energy balance and caused transient increases in concentrations of NEFA, acetate, and beta-hydroxybutyrate in plasma. Concentrations of beta-hydroxybutyrate and insulin in plasma were increased by butanediol, which is a potent ketone body precursor. Concentration of glycogen in liver was less in feed-restricted cows, whereas glycogen and total lipid were greater in cows given butanediol separately. Gluconeogenic capacity of liver slices was not different among groups. Addition of 1,3-butanediol to in vitro incubation media decreased oxidation of propionate to CO2. Neither feed restriction nor dietary 1,3-butanediol as separate treatments induced the fatty liver and ketosis observed in earlier experiments in which the two treatments were given together.

Animals↗