Immunomodulatory effects of mixed hematopoietic chimerism: immune tolerance in canine model of lung transplantation.

Long-term survival after lung transplantation is limited by acute and chronic graft rejection. Induction of immune tolerance by first establishing mixed hematopoietic chimerism (MC) is a promising strategy to improve outcomes. In a preclinical canine model, stable MC was established in recipients after reduced-intensity conditioning and hematopoietic cell transplantation from a DLA-identical donor. Delayed lung transplantation was performed from the stem cell donor without pharmacological immunosuppression. Lung graft survival without loss of function was prolonged in chimeric (n = 5) vs. nonchimeric (n = 7) recipients (p < or = 0.05, Fisher's test). There were histological changes consistent with low-grade rejection in 3/5 of the lung grafts in chimeric recipients at > or =1 year. Chimeric recipients after lung transplantation had a normal immune response to a T-dependent antigen. Compared to normal dogs, there were significant increases of CD4+INFgamma+, CD4+IL-4+ and CD8+ INFgamma+ T-cell subsets in the blood (p < 0.0001 for each of the three T-cell subsets). Markers for regulatory T-cell subsets including foxP3, IL10 and TGFbeta were also increased in CD3+ T cells from the blood and peripheral tissues of chimeric recipients after lung transplantation. Establishing MC is immunomodulatory and observed changes were consistent with activation of both the effector and regulatory immune response.

Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: a randomized controlled trial.

OBJECTIVE: To determine the safety and efficacy of a dietary supplement with a low dose of ephedra and caffeine in overweight/obese premenopausal female subjects. DESIGN: A 9-month, double-blind, randomized control study compared the efficacy and safety of a dietary supplement with ephedra and caffeine to a control supplement. SUBJECTS: Sixty-one healthy, premenopausal women with body mass index (BMI) from 27 to 39 kg/m2 were randomly assigned and received a dietary supplement (40 mg/day ephedra alkaloids, 100 mg/day caffeine, high potency mixture of vitamins, minerals, omega-3 fatty acids) or a control supplement for 9 months. EFFICACY: changes in body weight, body composition, lipids, insulin, leptin, adiponectin, ghrelin, and self-reports of physical activity, diet and quality of life indices. SAFETY: blood pressure, heart rate, electrocardiograms, urinalysis, blood histology, serum chemistry measures and self-reported symptoms. RESULTS: Forty-one women completed the study. The treatment group lost significantly more body weight (-7.18 kg) and body fat (-5.33 kg) than the control group (-2.25 and -0.99 kg, respectively), and showed significant declines in heart rate, serum cholesterol, triglycerides, cholesterol to high-density lipoprotein ratio, glucose, fasting insulin, and leptin. Blood pressure, electrocardiograms, other clinical chemistry measures, blood histology, urinalysis, and self-reported physical activity were similar in the groups. Minor symptoms included dry mouth, insomnia, nervousness and palpitations. The treatment group reported more energy and decreased appetite compared to controls and scored higher on a quality of life domain assessing vitality. CONCLUSION: A dietary supplement containing a low potency ephedra/caffeine mixture appeared safe and effective in causing loss of weight and body fat, and improving several metabolic parameters, including insulin sensitivity and lipid profiles when tested under physician supervision. Such supplements could be a useful tool to assist with weight loss.

Quantitative determination of ginsenosides by high-performance liquid chromatography-tandem mass spectrometry.

An HPLC-MS/MS method was developed for the quantitative determination of ginsenosides, which are the marker compounds for herbal products containing Panax ginseng (Korean or Chinese ginseng) and P. quinquefolius (American ginseng). Samples were extracted with BondElut C18 HF extraction columns and the concentrations of seven major ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1) were determined by reversed-phase HPLC-MS/MS employing a quadrupole-ion trap mass spectrometer. Both positive and negative electrospray ionisation techniques were evaluated. Positive ionisation spectra of these compounds gave strong sodium adduct molecular and sodium adduct dimer ions. Negative ionisation yielded the molecular ion primarily and was, therefore, used for analysis: quantitative determination was based on the most abundant product ions for each ginsenoside. The method was used to extract and analyse commercial samples of P. ginseng and P. quinquefolius.

Marrow transplants from unrelated donors for patients with aplastic anemia: minimum effective dose of total body irradiation.

Patients with aplastic anemia who do not have suitably HLA-matched, related donors generally receive immunosuppressive treatment as first-line therapy and are considered for transplantation from an unrelated donor only if they fail to respond to immunosuppressive treatment. In this setting, rates of transplantation-related morbidity and mortality have been high. We conducted a prospective study to determine the minimal dose of total body irradiation (TBI) sufficient to achieve sustained engraftment when it is used in combination with 3 cycles of 30 mg/kg of antithymocyte globulin (ATG) and 4 cycles of 50 mg/kg of cyclophosphamide (CY). We also wanted to determine the tolerability and toxicity of the regimen. The starting dosage of TBI was 3 x 200 cGy given over 2 days following CY/ATG. The TBI dose was to be escalated in increments of 200 cGy if graft failure occurred in the absence of prohibitive toxicity, and de-escalated for toxicity in the absence of graft failure. Twenty-one female and 29 male patients aged 1.3 to 46.5 years (median age, 14.4 years) underwent transplantation at 14 medical centers. The time interval from diagnosis to transplantation was 2.8 to 264 months (median, 14.5 months). All patients had been transfused multiple times and all had received 1 to 11 courses (median, 4 courses) of immunosuppressive treatment and other modalities of treatment. In 38 cases, the donors were HLA-A, -B and -DR phenotypically matched with the patients, and, in 12 cases, the donor phenotype differed from that of the recipient by 1 HLA antigen. Recipients of mismatched transplants were considered separately for TBI dose modification, and this study is still ongoing. Seven patients did not tolerate ATG and were prepared with 6 x 200 cGy of TBI plus 120 mg/kg of CY. Of the HLA-matched recipients prepared with CY/ATG/TBI, all 20 who received 3 x 200 or 2 x 200 cGy of TBI achieved engraftment, and 10 are alive. Of the 13 patients who received 1 x 200 cGy of TBI, 1 failed to engraft, and 8 are alive. Each of 10 patients who received an HLA-nonidentical transplant achieved engraftment, and 3 of 6 who were given 3 x 200 cGy of TBI, and 4 of 4 who were given 2 x 200 cGy are alive. Pulmonary toxicity occurred in 8 of 30 patients who were given 3 x 200 or 2 x 200 cGy of TBI concurrently with ATG and CY at 200 mg/kg, and in 2 of 13 patients who received 1 x 200 cGy of TBI, a pattern that suggests a decrease in toxicity with TBI dose de-escalation. Overall, the highest probability of survival (73%) was observed among patients who underwent transplantation within 1 year of diagnosis, compared with patients who underwent transplantation after a longer period of disease. In addition, younger patients (aged < or = 20 years) were more likely to survive than older patients (aged > 20 years). Thus, for patients with an HLA-matched, unrelated donor, a TBI dose of 200 cGy (in combination with CY/ATG) was sufficient to allow for engraftment without inducing prohibitive toxicity. As in previous studies, patient age and pretransplantation disease duration remain important prognostic factors.

Variability in commercial ginseng products: an analysis of 25 preparations.

BACKGROUND: Because dietary supplements are not subject to the same regulations that pharmaceuticals are, there is concern among medical professionals that these products may lack purity or potency. OBJECTIVE: To determine the variability in a range of ginseng herbal products available in the United States, we identified and measured the concentration of marker compounds by using HPLC and liquid chromatography-tandem mass spectrometry. DESIGN: Twenty-five commercial ginseng preparations from the genera Panax or Eleutherococcus were obtained from a local health food store and analyzed for 7 ginsenosides (marker compounds for Panax species, which include Asian and American ginseng) and 2 eleutherosides (marker compounds for Eleutherococcus senticosus, also known as Siberian ginseng). RESULTS: All plant products were correctly identified by botanical plant species (ie, Panax species or E. senticosus); however, concentrations of marker compounds differed significantly from labeled amounts. There was also significant product-to-product variability: concentrations of ginsenosides varied by 15- and 36-fold in capsules and liquids, respectively, and concentrations of eleutherosides varied by 43- and 200-fold in capsules and liquids, respectively. Although a systematic search for adulterants was not conducted, review of the HPLC and liquid chromatography-tandem mass spectrometry data suggest that no substances other than ginsenosides or eleutherosides were extracted from the plant material. CONCLUSION: Our data suggest that US ginseng products are correctly labeled as to plant genus; however, variability in concentrations of marker compounds suggests that standardization may be necessary for quality assurance and that characterization of herbal products should be considered in the design and evaluation of studies on herbal products.

Heavily smoking women who cannot quit in pregnancy: evidence of pharmacokinetic predisposition.

SUMMARY: Smoking in pregnancy is associated with a well-characterized increase in perinatal risks. Despite their wish to discontinue smoking, some pregnant women cannot stop. To characterize nicotine and cotinine levels in women who could not quit smoking after the first trimester, the authors recruited 19 white women (age 17-41 years) between 14-23 weeks of gestation who could not quit smoking. They started smoking at ages 11-22 years (mean 14.5) and smoked for 17 +/- 6 years. They had their first cigarettes 5-60 minutes after waking up (mean 12). Nicotine levels were compared with those expected in white patients in the general population, and the cotinine levels per cigarette smoked were compared with the population-based values. Sixteen of the 19 women had nicotine levels substantially lower than those expected. The mean level of serum cotinine produced by one cigarette per day was 19.1 +/- 15.8 ng/mL (range 6.1-67). The expected levels in white patients in the general population are 13 +/- 7.7 ng/mL. The data suggest that pregnant women who cannot quit heavy smoking in the second trimester form a selective group with pharmacokinetic predisposition to a high rate of nicotine metabolism.

Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis.

BACKGROUND: Cyclosporine (CsA) therapy must often be continued during pregnancy to maintain maternal health in such conditions as organ transplantation and autoimmune disease. This meta-analysis was performed to determine whether CsA exposure during pregnancy is associated with an increased risk of congenital malformations, preterm delivery, or low birthweight. METHODS: Various health science databases were searched to identify relevant articles. Articles selected for inclusion in the study were required to be free of any apparent selection bias and report outcomes in at least 10 newborns exposed to CsA in utero, specifically commenting on the presence or absence of congenital malformations. Article selection and data extraction were performed by two independent reviewers, with adjudication in cases of disagreement. To assess risks of CsA exposure, a summary odds ratio was calculated. Prevalence of malformations was calculated as a rate for all cyclosporine-exposed live births and for the subgroups identified. Ninety-five percent confidence intervals were constructed for both the odds ratio and prevalence rates. RESULTS: Fifteen studies (6 with control groups of transplant without use of cyclosporine; total patients: 410) met the inclusion criteria for major malformations, 10 for preterm delivery (4 with control groups; total patients: 379) and 5 for low birth weight (1 with control groups; total number of patients: 314). The calculated odds ratio of 3.83 for malformations did not achieve statistical significance (CI 0.75-19.6). The overall prevalence of major malformations in the study population (4.1%) also did not vary substantially from that reported in the general population. OR for prematurity [1.52 (CI 1.00-2.32)] did not reach statistical significance although the overall prevalence rate was 56.3%. The OR for low birth weight [1.5 (CI 0.95-2.44 based on 1 study)]. CONCLUSIONS: CsA does not appear to be a major human teratogen. It may be associated with increased rates of prematurity. More research is needed to evaluate whether cyclosporine increases teratogenic risk.

Predicting Farnsworth Lantern success with a six-plate series of the Ishihara pseudoisochromatic plates.

The Farnsworth Lantern (FALANT) is the definitive color vision test for the Navy, Marine Corps, and Coast Guard. It is also the definitive color vision test for aviation personnel in the Army. Results from it are also accepted by the Federal Aviation Administration. For various reasons, it is desirable to have an alternative test that can predict success (i.e., a passing score) on the FALANT. In 1991, it was shown that a 14-plate series of Ishihara pseudoisochromatic plates could predict FALANT success provided the proper passing criteria was chosen. Interest has arisen regarding whether or not a 6-plate series of Ishihara plates can predict FALANT success. A study was undertaken to answer this question. It appears that a 6-plate series of Ishihara pseudoisochromatic plates can predict FALANT success.

Adherence of adoptively transferred alloreactive Th1 cells in lung: partial dependence on LFA-1 and ICAM-1.

T helper type 1 (Th1) cells are important effectors in a number of immune-mediated lung diseases. We recently described a murine model of lung injury induced by adoptive transfer of cloned alloreactive Th1 cells. To investigate mechanisms that result in injury to the lung, we studied the in vivo distribution of (51)Cr-labeled Th1 cells. One hour after intravenous administration, >85% of injected radioactivity was left in the lung, and at 24 h, 40% of radioactivity was left in the lung. Adherence of Th1 cells in the lung was significantly inhibited by neutralizing antibody to lymphocyte function-associated antigen-1. Th1 cell adherence also was decreased in lungs of mice deficient in intercellular adhesion molecule-1 (ICAM-1). Th1 cell transfer further induced expression of ICAM-1 and vascular cell adhesion molecule-1 in the lung. Vascular cell adhesion molecule-1-immunoreactive protein was markedly induced in lung endothelium by alloreactive Th1 cells. These findings indicate that Th1 cells localize in normal lung by a mechanism involving lymphocyte function-associated antigen-1 and ICAM-1. Alloreactive cells further induce endothelial adhesion molecules that may facilitate recruitment of inflammatory cells to the lung and amplify Th1 cell-induced lung injury.

Neutralization of tumor necrosis factor-alpha action delays but does not prevent lung injury induced by alloreactive T helper 1 cells.

BACKGROUND: Lung injury occurs frequently after allogeneic bone marrow transplantation in association with graft-versus-host disease, an immune response that involves both cellular and cytokine components. In a murine model, we recently showed that cloned alloreactive T helper (Th)1 cells can cause lung injury associated with increased production of tumor necrosis factor (TNF)-alpha by alveolar macrophages (J Immunol 1998; 161: 1913). METHODS: To evaluate the role of TNF-alpha in this model, we injected in vitro-activated Th1 cells into the following: (1) recipients deficient in receptors for TNF; (2) C57BL/6 control mice; (3) C57BL/6 mice, pretreated with soluble TNFRIIFc (a dimorphic high-affinity TNF antagonist); (4) mice expressing TNFRIIFc transgene under control of the surfactant apoprotein C promoter (SPCTNFRIIFc); and (5) wild-type littermate controls (C57BL/6) (n=3-6 mice/group). RESULTS: At 1 and 3 days after i.v. Th1 cell transfer, recipients were killed for analysis of lung histology, bronchoalveolar lavage (BAL) protein, and BAL cell counts. Control mice (wild type) at day 1 after injection had a mild to moderate mononuclear perivasculitis and increased interstitial cellularity. At day 3, lesions were more severe and perivasculitis also involved larger veins. TNFR-deficient mice had normal lung or minimal lung inflammation at day 1. At day 3, perivasculitis of medium-sized vessels was present, but there was no apparent involvement of larger veins. Results in mice treated with soluble TNFRIIFc and transgenic mice (SPCsTNFRIIFc) were similar to controls. BAL protein and BAL cell counts did not differ between any of the experimental groups. CONCLUSIONS: We conclude that lung inflammation induced by Th1 cells may be only delayed when TNF-alpha action is blocked. The persistence of abnormalities indicates that other proinflammatory pathways are involved in injury caused by these cells.

Hypnosis and asthma: a critical review.

Asthma is among the most common chronic diseases of the western world and has significant effects on patients' health and quality of life. Asthma is typically treated with pharmaceutical products, but there is interest in finding nonpharmaceutical therapies for this condition. Hypnosis has been used clinically to treat a variety of disorders that are refractive to pharmaceutical-based therapies, including asthma, but relatively little attention has been given recently to the use of clinical hypnosis as a standard treatment for asthma. Significant data suggest that hypnosis may be an effective treatment for asthma, but it is premature to conclude that hypnosis is unequivocally effective. Studies conducted to date have consistently demonstrated an effect of hypnosis with asthma. More and larger randomized, controlled studies are needed. Existing data suggest that hypnosis efficacy is enhanced in subjects who are susceptible to the treatment modality, with experienced investigators, when administered over several sessions, and when reinforced by patient autohypnosis. Children in particular appear to respond well to hypnosis as a tool for improving asthma symptoms.

Effects of ginseng components on c-DNA-expressed cytochrome P450 enzyme catalytic activity.

Because little is known about the interactions between herbal products and standard medications, the effects of seven ginsenosides and two eleutherosides (active components of the ginseng root) on the catalytic activity of c-DNA expressed cytochrome P450 isoforms were studied in in vitro experiments. Increasing concentrations of ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1 and eleutherosides B and E were incubated with a panel of recombinant human CYP isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) and their effects on the conversion of specific surrogate substrates measured fluorometrically in a 96-well plate format. For each test substance, the IC50 (the concentration required to inhibit the metabolism of the surrogate substrates by 50%) was estimated and this value compared with that obtained for positive control inhibitory drugs furafylline, sulfaphenazole, tryanylcypromine, quinidine, and ketoconizole. Of the components tested, three ginsenosides (Rd, Rc, and Rf) modified the activity of the recombinant enzymes. Ginsenoside Rd produced weak inhibitory activity against the surrogate substrates for CYP3A4 and CYP2D6 and even weaker inhibitory activity against the surrogate substrates for CYP2C19 and CYP2C9. The IC50 values of 58 and 74 uM for the two substrates for CYP3A4 are orders of magnitude higher than that for the potent inhibitor ketoconazole used as a positive control. Ginsenoside Rc produced an increase in the activity of CYP2C9 (70% at 200 uM) and ginsenoside Rf produced an increase in the activity of CYP3A4 (54% at 200 uM). The biological significance of this is unclear at this time. Enzyme "activation", the process by which direct addition of one compound to an enzyme enhances the rate of reaction of the substrate, has been observed in a number of cases with P450 enzymes; however, a matrix effect caused by the test compound fluorescing at the same wavelength as the metabolite of the marker substrate cannot be ruled out. In summary, these studies suggest that the ginsenosides and eleutherosides tested are not likely to inhibit the metabolism of coadministered medications in which the primary route of elimination is via cytochrome P450; the potential of ginsenosides to enhance the catalysis of certain substrates requires further investigation.

Idiopathic pneumonia after bone marrow transplantation: cytokine activation and lipopolysaccharide amplification in the bronchoalveolar compartment.

OBJECTIVE: To determine whether idiopathic pneumonia syndrome (IPS), a form of noninfectious lung injury that follows bone marrow transplantation, is associated with cytokine activation and increased susceptibility to lipopolysaccharide (LPS). DESIGN: Case series. SETTING: Tertiary referral center for marrow transplantation. PATIENTS: Recipients with biopsy-confirmed IPS; normal volunteers and marrow transplant recipients without IPS were analyzed as controls. MEASUREMENTS AND MAIN RESULTS: Levels of lymphocyte and macrophage-derived cytokines as well as components of the LPS, LPS-binding protein (LBP), and CD14 system in bronchoalveolar lavage (BAL) fluid were determined. We found evidence of increased vascular permeability (BAL protein) and inflammatory cytokine activation (interleukin-1, interleukin-2, interleukin-6, and tumor necrosis factor-alpha) in patients with IPS. Patients without IPS had BAL fluid cytokine and protein levels that were similar to levels in BAL fluid from normal volunteers. Moreover, components of the LPS amplification system (LBP and soluble CD14) were increased in patients with IPS but not in patients without IPS. CONCLUSIONS: These results provide direct evidence for proinflammatory cytokine activation in IPS and suggest that these patients might be at increased risk for LPS-mediated injury through the LBP amplification pathway.

Mushrooms, tumors, and immunity.

Medicinal properties have been attributed to mushrooms for thousands of years. Mushroom extracts are widely sold as nutritional supplements and touted as beneficial for health. Yet, there has not been a critical review attempting to integrate their nutraceutical potential with basic science. Relatively few studies are available on the biologic effects of mushroom consumption, and those have been performed exclusively in murine models. In this paper, we review existing data on the mechanism of whole mushrooms and isolated mushroom compounds, in particular (1-->3)-beta-D-glucans, and the means by which they modulate the immune system and potentially exert tumor-inhibitory effects. We believe that the antitumor mechanisms of several species of whole mushrooms as well as of polysaccharides isolated from Lentinus edodes, Schizophyllum commune, Grifola frondosa, and Sclerotinia sclerotiorum are mediated largely by T cells and macrophages. Despite the structural and functional similarities of these glucans, they differ in their effectiveness against specific tumors and in their ability to elicit various cellular responses, particularly cytokine expression and production. Unfortunately, our data base on the involvement of these important mediators is still rather limited, as are studies concerning the molecular mechanisms of the interactions of glucans with their target cells. As long as it remains unclear what receptors are involved in, and what downstream events are triggered by, the binding of these glucans to their target cells, it will be difficult to make further progress in understanding not only their antitumor mechanisms but also their other biological activities.

Endoscopic and histologic diagnosis of intestinal graft-versus-host disease after marrow transplantation.

BACKGROUND: Gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation presents a range of upper gastrointestinal endoscopic and histologic abnormalities. Recognition of these sometimes subtle abnormalities is critical for directing specific therapy. METHODS: Endoscopic and histologic abnormalities in 10 patients with gastrointestinal graft-versus-host disease are reviewed to detail the spectrum of findings. RESULTS: The endoscopic appearance of the stomach and duodenum varies from subtle mucosal erythema and edema to frank ulceration and mucosal slough. Histologic findings include crypt epithelial cell apoptosis and dropout, crypt destruction, and variable lymphocytic infiltration of the epithelium and lamina propria. The involvement may vary from diffuse and uniform to focal, with either the stomach or the duodenum appearing much more involved. CONCLUSIONS: Endoscopic evaluation of the stomach and duodenum and histologic evaluation of biopsies of the gastric antrum can be used to diagnose gastrointestinal graft-versus-host disease. The gross appearance of the mucosa and the histology of gastric biopsies are mutually complementary. However, both the endoscopic evaluation and the histology of the upper gut can underestimate the severity of acute graft-versus-host disease elsewhere in the intestine unless extensive mucosal sloughing is seen.

Transforming growth factor-alpha deficiency reduces pulmonary fibrosis in transgenic mice.

Despite evidence that implicates transforming growth factor-alpha (TGF-alpha) in the pathogenesis of acute lung injury, the contribution of TGF-alpha to the fibroproliferative response is unknown. To determine whether the development of pulmonary fibrosis depends on TGF-alpha, we induced lung injury with bleomycin in TGF-alpha null-mutation transgenic mice and wild-type mice. Lung hydroxyproline content was 1.3, 1.2, and 1.6 times greater in wild-genotype mice than in TGF-alpha-deficient animals at Days 10, 21, and 28, respectively, after a single intratracheal injection of bleomycin. At Days 7 and 10 after bleomycin treatment, lung total RNA content was 1.5 times greater in wild-genotype mice than in TGF-alpha-deficient animals. There was no significant difference between mice of the two genotypes in lung total DNA content or nuclear labeling indices after bleomycin administration. Wild-genotype mice had significantly higher lung fibrosis scores at Days 7 and 14 after bleomycin treatment than did TGF-alpha-deficient animals. There was no significant difference between TGF-alpha-deficient mice and wild-genotype mice in lung inflammation scores after bleomycin administration. To determine whether expression of other members of the epidermal growth factor (EGF) family is increased after bleomycin-induced injury, we measured lung EGF and heparin-binding- epidermal growth factor (HB-EGF) mRNA levels. Steady-state HB-EGF mRNA levels were 321% and 478% of control values in bleomycin-treated lungs at Days 7 and 10, respectively, but were not significantly different in TGF-alpha-deficient and in wild-genotype mice. EGF mRNA was not detected in normal or bleomycin-treated lungs of mice of either genotype. These results show that TGF-alpha contributes significantly to the pathogenesis of pulmonary fibrosis after bleomycin-induced injury, and that compensatory increases in other EGF family members do not occur in TGF-alpha-deficient mice.

Lymphocytic gastritis resembling graft-vs.-host disease following autologous hematopoietic cell transplantation.

Although cutaneous graft-vs.-host disease (GVHD) has been noted after autologous hematopoietic cell transplantation, intestinal involvement has not been well documented. We evaluated 197 patients undergoing autologous transplantation for intestinal symptoms; the source for hematopoietic cells was marrow (n=32), peripheral blood stem cells (n=146), or both (n=19). Patients with persistent nausea, vomiting, and anorexia after day 20 underwent upper intestinal endoscopy and mucosal biopsy. Eight patients (4.1%) had diffuse edema, erythema of gastric mucosa, and histological evidence of lymphocytic gastritis with focal apoptosis of crypt epithelial cells-typical of the findings in acute GVHD. All studies for viral, fungal, or bacterial causes were negative. Two patients showed evidence of GVHD in skin and liver, respectively. All patients received 1 mg/kg/day of oral prednisone for 10 days; symptomatic improvement often occurred within days of therapy onset. At the end of corticosteroid treatment, complete resolution of symptoms was seen in all eight patients. In one patient, elevated serum alkaline phosphatase levels gradually normalized over the ensuing 3-4 weeks. When followed up 3 months after treatment, all patients remained symptom-free without evidence of recurrent intestinal symptoms. We concluded that recipients of autologous hematopoietic cells may develop intestinal symptoms caused by a lymphocytic gastritis that is typical of acute GVHD. Patients with this syndrome promptly responded to treatment of a short course of prednisone. The pathogenesis of gastric epithelial damage after autologous transplant is unknown.