Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic hepatitis due to putative non-A, non-B, non-C hepatitis occurring in an individual who is negative for HBV and HCV markers has been identifiable only recently. Little or nothing is known about its natural history or response to interferon therapy. In the present study, 13 subjects with chronic non-A, non-B, non-C hepatitis were treated with interferon for 6 months (5 million units, three times per week). Prior to and after 6 months of therapy and again 6 weeks after discontinuing interferon therapy, each subject underwent a liver biopsy. These tissues were used to define the histopathology, the character of the cellular infiltrate within the liver, and the changes in histopathology and inflammatory infiltrate achieved in response to interferon therapy and withdrawal. No differences for age, gender, initial AST, bilirubin, histopathology, or Knodell score were evident between responders (n = 7) and non-responders (n = 6). Only the number of NK cells was altered significantly as a result of IFN treatment and distinguished responders from non-responders. These data demonstrate that: (1) chronic non-A, non-B, non-hepatitis can be treated with interferon; (2) interferon activates NK cells and enhances hepatocyte expression of Class II MHC antigens; and (3) interferon also increases the number of CD3, CD4, and CD8 cells found within the liver but these changes do not distinguish between responders and non-responders.
...
PMID:Treatment of putative non-A, non-B, non-C hepatitis with alpha interferon: a preliminary trial. 793 74

The mechanism(s) of rejection or tolerance induction is a competitive, complex process that presumably involves interactions between multiple subpopulations of T lymphocytes. We investigated the roles of CD8+ cytolytic and CD4+ helper T cells in rat strains that tolerate liver allografts and that differ at both the major histocompatibility complex (MHC) (RT1) and minor histocompatibility genes. Orthotopic liver transplantation (OLT) with arterial reconstruction was performed with Brown Norway (BN) (RT1n) donors and Lewis (RT1(1)) recipients, some of which were untreated, others treated with anti-CD8 antibody, and still others treated with anti-CD4 antibody. Liver graft rejection was monitored for 28 days on the basis of two criteria: (1) serum levels of AST enzyme at 3-day intervals and (2) liver biopsies at weekly intervals and at the time of sacrifice at the end of the study period. In the untreated control group, an elevation of AST was found to peak at day 6 after grafting, and it remained elevated until day 28 (AST 542 +/- 72 U/l). Histologically, signs of severe rejection were first observed on day 9; these changed to moderate rejection about day 21 and to mild rejection by day 28, when the animals were sacrificed. Recipients pre-treated with anti-CD8 demonstrated a significant elevation of AST within 6 days that, unlike in the control recipients, continued to rise sharply through the observation period (AST 1127 +/- 181 U/l, P = 0.009 vs control group). Liver biopsies showed mild rejection at day 9 and moderate rejection at days 21 through 28. Recipients pretreated with anti-CD4 showed a time course of enzyme elevation and severity of rejection that was not significantly different from that observed in the control group. However, anti-CD4 treatment resulted in only 75% depletion of CD4+ cells in peripheral blood as compared to complete elimination of CD8+ cells following anti-CD8 treatment. Functional studies of spleen and liver-infiltrating lymphocytes obtained after 28 days showed low proliferative response in mixed lymphocyte culture with both BN and PVG stimulator spleen and lymph node cells. These results suggest that in this donor/recipient combination, removal of CD8+ cells increases the severity of rejection as demonstrated by a progressive rise in AST and histology. Moreover, OLT in this combination results in a profound, nonspecific inhibition of proliferative T-cell responses to MHC alloantigens.
...
PMID:Liver allograft rejection in rats depleted of CD8+ cells. 887 94

Hepatocytes constitute the principal site of listerial replication in the livers of mice infected i.v. CD8+ T lymphocytes play a predominant role in the host defenses to Listeria monocytogenes. In vitro experiments by others undertaken to delineate the functions of CD8+ T lymphocytes have focused primarily on their interaction with Listeria-infected macrophages. Such experiments do not address directly the role of CD8+ T lymphocytes in eliminating the bulk of Listeria replicating within the liver. Here, we report that immune CD8+ T cells at an E:T cell ratio > or = 10:1 lysed Listeria-infected hepatocytes as judged by the following two criteria. Aspartate aminotransferase activity in the culture supernatants, indicative of hepatocyte damage, increased significantly. Conversely, infected hepatocytes cocultured with immune CD8+ T cells exhibited a marked reduction in viable intracellular Listeria assessed by CFUs. Neither immune CD4+ T cells nor nonimmune CD8+ T cells caused a similar increase in aspartate aminotransferase activity released or a decrease in intracellular bacteria. Immune CD8+ T cell-mediated lysis of infected hepatocytes was restricted by classical MHC class I (H-2Kb) molecules and was inhibited by the presence of either brefeldin A or mAb specific for CD8. These results suggest that the predominant role of CD8+ T lymphocytes in host resistance to listerial infections of the liver may be due to their capacity to lyse infected hepatocytes.
...
PMID:Immune CD8+ T lymphocytes lyse Listeria monocytogenes-infected hepatocytes by a classical MHC class I-restricted mechanism. 897 1

We encountered six patients with pneumonitis related to blended chinese traditional medicine (Kampo). The duration of treatment with kampo ranged from 14 to 110 days (mean: 38 days). The most common complaints were dyspnea, fever, and dry coughing. Fine crackles were heard at the bases of both lungs. Abnormal laboratory findings included high values of C-reactive protein and glutamic-oxaloacetic transaminase in all patients, lactate dehydrogenase in 5 patients, and eosinophil count in 1 patient. Chest X-ray films and CT films revealed diffuse reticulo-nodular interstitial shadows with consolidation in both lung fields in 3 patients and pleural effusion in 1 patient. Bronchoalveolar lavage was done in 4 patients; examination of the lavage fluid showed lymphocyte alveolitis, either pure or associated with neutrophilia and eosinophilia in 3 patients. Inverted CD4/CD8 lymphocyte ratios were found in 3 patients. Transbronchial lung biopsy was done in 4 patients and specimens from 3 of those 4 showed organizing pneumonitis with thickening of alveolar septa. Lymphocyte stimulation tests were positive in 4 patients. Discontinuation of the drug (2 patients) or administration of corticosteroids (4 patients) was followed by rapid improvement. Patients being treated with kampo preparations should be observed for signs and symptoms of drug-induced pneumonitis.
...
PMID:[Six patients with pneumonitis related to blended Chinese traditional medicines]. 902 15

1. This study was performed to test the hypothesis that the exercise-induced increase in circulating cytokine levels is associated with muscle damage. Nine healthy young male subjects performed two high-intensity bicycle exercise trials separated by two weeks. The first trial consisted of 30 min of normal bicycle exercise (concentric exercise), whereas the second consisted of 30 min of braking with reversed revolution (eccentric exercise). The work loads were chosen to give the same increases in heart rate and catecholamine levels in the blood during each trial. 2. Significant increases (P < 0.05) in plasma concentration of creatine kinase (CK), aspartate aminotransferase and alanine aminotransferase were observed only after the eccentric exercise. Furthermore, the level of interleukin-6 (IL-6) in serum increased significantly after the eccentric exercise and was significantly correlated to CK concentration in the following days, whereas no significant changes were found after the concentric exercise. 3. The total concentration of lymphocytes increased significantly (P < 0.05) as a result of eccentric compared with concentric exercise. This was mainly due to a significantly more pronounced recruitment of natural killer (NK) cells and CD8 positive cells (CD8+ cells) during the eccentric trial. However, no significant differences between the two types of work were found in regard to the circulating concentration of monocytes. The concentration of neutrophils was only significantly increased 2 h after the concentric exercise. 4. The finding that high-intensity eccentric exercise caused a more pronounced increase in the plasma level of IL-6, compared with concentric exercise, supports the hypothesis that the post-exercise cytokine production is related to skeletal muscle damage. The fact that no differences between eccentric and concentric exercise were found in the recruitment of most blood mononuclear cell subsets to the blood supports the hypothesis that the exercise-induced increase in plasma catecholamines is a major determinant of the mobilization of these cells into the blood. However, as eccentric exercise caused a more pronounced increase in the concentration of NK cells and CD8+ cells, factors involved in muscle damage may also contribute to the recruitment of these cells.
...
PMID:Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage. 913 Jan 76

In 14 patients with polymyositis (PM), 5 patients (2 males and 3 females) were positive for anti-hepatitis C virus (HCV) antibody measured by a second generation assay. We analysed the clinical characteristics and histopathological findings of the biopsied muscles from those 5 patients. They aged from 42 to 65 years averaging 53.6 years. Two asymptomatic patients visited our hospital due to elevated muscle enzyme levels, who had slight weakness in their orbicularis oculi and neck muscles on physical examination. The other 3 patients had moderate weakness of the proximal muscles. Anti-nuclear antibody was positive in 2 of the 5 patients and anti-Jo 1 antibody was negative in all patients. The serum enzymes elevated were creatine kinase (215-2, 207 (IU/l)) and glutamate oxaloacetate transaminase (40-119 (KU)). HCV-RNA was positive in the sera of 4 patients examined. All muscle biopsy specimens revealed variation in fiber size with inflammatory cellular infiltration and observed degenerating and regenerating fibers. The scant infiltration type was observed in 2 asymptomatic patients in whom the infiltrated cells were CD4 positive. The endomysial infiltration type was observed in 3 symptomatic patients; CD8 positive cells were found focally to diffusely in 2 patients examined. The expression of class 1 molecules from the major histocompatibility complex was detected mainly in infiltrated fibers to variable degrees. All of the patients showed a good response to the initial steroid therapy. The present study suggests that autoimmune reaction related to HCV infection causes myositis, therefore anti-HCV antibody should be checked in cases of PM.
...
PMID:[Clinical characteristics and muscle histopathology in polymyositis positive anti-hepatitis with C virus antibody]. 921 18

Propagermanium is an organic germanium compound with immunopotentiating activity. We examined the hepatoprotective effect of propagermanium and its mechanism in an experimental animal model of acute liver injury induced with Corynebacterium parvum (C. parvum) and lipopolysaccharide (LPS) injection. Oral pretreatment with propagermanium decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in a dose-dependent manner. Significant attenuation of ALT and AST activity was obtained at a dose of 3 mg/kg. Administration of propagermanium also inhibited the infiltration of mononuclear cells into the liver of mice induced by C. parvum/LPS. Immunohistochemical examination revealed infiltration of the liver by CD4-, CD8-, CD11b- and Gr-1-positive cells. Propagermanium prevented CD4- and CD11b-positive cells from infiltrating the liver. In this animal model, blood cytokine levels increased rapidly after LPS injection, causing severe hepatitis. Notably, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important mediators of the progress of liver injury. We demonstrated that propagermanium reduced IFN-gamma production by 53% at a dose of 3 mg/kg and also significantly inhibited the production of interleukin-12 (IL-12). These results indicate that propagermanium inhibits cell infiltration in the liver and cytokine production, and improves massive liver injury in C. parvum/LPS mice.
...
PMID:Hepatoprotective effect of propagermanium on Corynebacterium parvum and lipopolysaccharide-induced liver injury in mice. 971 10

Little is understood of the anatomical fate of activated T lymphocytes and the consequences they have on the tissues into which they migrate. Previous work has suggested that damaged lymphocytes migrate to the liver. This study compares class I versus class II major histocompatibility complex (MHC)-restricted ovalbumin-specific T cell antigen receptor (TCR) transgenic mice to demonstrate that after in vivo activation with antigen the emergence of CD4(-)CD8(-)B220(+) T cells occurs more frequently from a CD8(+) precursor than from CD4(+) T cells. Furthermore, this change in phenotype is conferred only by the high affinity native peptide antigen and not by lower affinity peptide variants. After activation of CD8(+) cells with only the high affinity peptide, there is also a dramatically increased number of liver lymphocytes with accompanying extensive hepatocyte damage and elevation of serum aspartate transaminase. This was not observed in mice bearing a class II MHC-restricted TCR. The findings show that CD4(-)CD8(-)B220(+) T cells preferentially derive from a CD8(+) precursor after a high intensity TCR signal. After activation, T cells can migrate to the liver and induce hepatocyte damage, and thereby serve as a model of autoimmune hepatitis.
...
PMID:Liver damage preferentially results from CD8(+) T cells triggered by high affinity peptide antigens. 974 33

The indolizidine alkaloid swainsonine, a potent inhibitor of Golgi alpha-mannosidase II, has been shown to reduce tumor cell metastasis, enhance cellular immune responses, and reduce solid tumor growth in mice. In our previous Phase I study, swainsonine administered by 5-day continuous infusion inhibited L-phytohemagglutinin-reactive N-linked oligosaccharide expression on peripheral blood lymphocytes. Significant toxicities included edema and elevated serum aspartate aminotransferase (AST). One patient with head and neck cancer had objective (>50%) tumor remission. Two patients showed symptomatic improvement. The objectives of this Phase IB trial were to examine the pharmacokinetics, toxicities, and biochemical effects of bi-weekly oral swainsonine at escalating dose levels (50-600 microgram/kg) in 16 patients with advanced malignancies and 2 HIV-positive patients unsuitable for conventional therapy. Eastern Cooperative Oncology Group performance status was </=2. The maximum tolerated dose was defined as 300 microgram/kg/day due primarily to serum AST abnormalities and dyspnea. Other adverse events present in >20% of patients included increase in serum AST (all patients), fatigue (n = 9), anorexia (n = 6), dyspnea (n = 6), and abdominal pain (n = 4). Inhibition of Golgi alpha-mannosidase II occurred in a dose-dependent manner. Examination of immunological parameters revealed a transient decrease in CD25(+) peripheral blood lymphocytes and, in seven of eight patients, an increase in CD4(+):CD8(+) ratios at 2 weeks. Serum drug levels peaked 3-4 h following a single oral dose in most patients and were proportional to dose at levels >/=150 microgram/kg. We conclude that oral swainsonine is tolerated by chronic intermittent administration at doses up to 150 microgram/kg/day. Adverse events considered drug related were similar to those observed in the infusional study but with fatigue and neurological effects also noted. Investigations of alternative dosing schedules with low starting doses are suggested for further clinical testing.
...
PMID:Phase IB clinical trial of the oligosaccharide processing inhibitor swainsonine in patients with advanced malignancies. 981 86

The variable manifestations of infectious mononucleosis rarely cause clinicians to suspect primary Epstein-Barr virus or cytomegalovirus infection; consequently, costly diagnostic tests and unnecessary treatments are undertaken. Seventeen cases of clinically atypical and 11 cases of clinically typical infectious mononucleosis were diagnosed through screening for atypical and apoptotic lymphocytes in the peripheral blood samples by means of an automated hematologic analyzer. Atypical and typical cases did not differ significantly with respect to peripheral white blood cell counts; percentages of lymphocytes, atypical lymphocytes, CD4(+) lymphocytes, human leukocyte antigen--DR positivity in CD3 lymphocytes, or apoptotic cells in blood smear after incubation; or levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase. Only the percentage of CD8(+) lymphocytes was significantly higher in patients with typical infectious mononucleosis than it was in patients with atypical infectious mononucleosis. Because certain atypical cases of infectious mononucleosis display laboratory abnormalities that are characteristic of typical infectious mononucleosis, enhanced awareness can help in the diagnosis.
...
PMID:Diagnosis of atypical cases of infectious mononucleosis. 1138 99


1 2 3 4 5 6 7 Next >>

---