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

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis B virus (HBV) reactivation of various degrees of severity, including fulminant hepatitis, may develop in 20-50% of hepatitis B virus surface antigen (HbsAg)-positive patients undergoing immunosuppressive or cytostatic treatment. Lamivudine is a nucleoside analogue that can directly suppress HBV replication. We have performed a pilot study to test the efficacy and tolerability of lamivudine as a primary prophylaxis of HBV reactivation in 20 consecutive patients treated for haematological malignancies, mainly of lymphoid origin. Lamivudine, 100 mg/d, was given orally from the start until 1 month after the end of chemotherapy, which included corticosteroids and/or purine analogues in 85% of cases. It was well tolerated and did not cause any unexpected reduction of cytostatic drugs dosages. The chemotherapy programme was completed in all patients without modifications. A transient threefold increase in serum amylase was observed in one case. HBV-DNA levels decreased in six out of six patients (P = 0.039) and ALT levels in five out of six patients (P = 0.057) whose serum levels were abnormal at the onset of therapy. Two patients developed transient hepatitis. HBV reactivation was documented in only one of these patients who had stopped lamivudine 1 month before. No signs of HBV reactivation were detected both during and after treatment in 18 patients with a median follow-up of 6 months (range 3-12). Thus, primary prophylaxis with lamivudine may be a well tolerated and effective method to reduce the frequency of chemotherapy-induced HBV reactivation in chronic HBsAg carriers.
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PMID:Primary prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg carriers with lymphoid malignancies treated with chemotherapy. 1172 10

We investigated the effects of various anesthetic agents on hepatic and splenic injury in mice. Three and six hours after intraperitoneal injection of TBE, intramuscular injection of ketamine/xylazine combination (K/X), intraperitoneal injection of pentobarbital (PB), and inhalation of isoflurane (IF), or intraperitoneal and intramuscular injection of control saline, mice were exsanguinated and serum was obtained for measurement of hepatic aspartate transaminase (AST), alanine transaminase (ALT) and gamma-glutamyltransferase (GGT). The spleen and liver also were obtained, and sections were examined by use of routine light microscopy for pathologic changes and for apoptosis, as determined by use of the in situ terminal deoxynucleotidyl transferase-mediated dUPT nick-end-labeling (TUNEL) histochemical analysis. Three hours after TBE or K/X administration, AST activity increased three- to fourfold above that in untreated and saline-injected control animals, and remained high at six hours. Administration of PB did not effect AST activity at three hours, but there was a significant increase at six hours. Activity of ALT was non-significantly increased three hours after TBE and K/X, but not PB administration. Administration of IF had no effect on hepatic enzyme activities, and GGT was not increased after administration of any of the agents. Markedly increased apoptosis was observed in splenic follicles and in hepatic Kupffer and endothelial cells at three hours after TBE and K/X administration, but apoptosis decreased to control levels by six hours. Increased apoptosis was not observed after IF administration. Administration of TBE and K/X causes injury to lymphocytes and to hepatic Kupffer and endothelial cells within three hours, and PB administration induces changes within six hours. Thus, use of these anesthetic agents should be avoided when experiments are being designed to test short-term effects of an experimental intervention on the spleen and possibly on all lymphoid tissues. In addition, they also should be avoided in experiments testing effects on hepatic tissue.
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PMID:Early effects of tribromoethanol, ketamine/xylazine, pentobarbitol, and isoflurane anesthesia on hepatic and lymphoid tissue in ICR mice. 1190 Apr 15

Gallium arsenide is used primarily to make light- emitting diodes, lasers, laser windows, and photodetectors and in the photoelectronic transmission of data through optical fibers. Gallium arsenide was nominated for study because of its widespread use in the microelectronics industry, the potential for worker exposure, and the absence of chronic toxicity data. Male and female F344/N rats and B6C3F1 mice were exposed to gallium arsenide particles (greater than 98% pure; mass median aerodynamic diameter = 0.8 to 1.0 &mgr;m) by inhalation for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, and the frequency of micronuclei was determined in the peripheral blood of mice exposed to gallium arsenide for 14 weeks. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to particulate aerosols of gallium arsenide with a mass median aerodynamic diameter of approximately 1 &mgr;m at concentrations of 0, 1, 10, 37, 75, or 150 mg/m(3) by inhalation, 6 hours per day, 5 days per week, for 16 days. All rats survived to the end of the study. The final mean body weights of all exposed groups of males and females were similar to those of the chamber controls. Compared to chamber controls, the liver and lung weights of males exposed to 1 mg/m(3) or greater and females exposed to 10 mg/m(3) or greater were increased; the thymus weights of all exposed groups of males were decreased. Gallium arsenide particles were visible in the alveolar spaces and, to a lesser extent, within alveolar macrophages of exposed rats. Moderate proteinosis (surfactant mixed with small amounts of fibrin) and minimal histiocytic cellular infiltrate were observed in the alveoli of exposed males and females. Epithelial hyperplasia and squamous metaplasia of the larynx were observed primarily in males exposed to 150 mg/m(3). 16-DAY STUDY IN MICE: Groups of five male and four or five female mice were exposed to particulate aerosols of gallium arsenide with a mass median aerodynamic diameter of approximately 1 &mgr;m at concentrations of 0, 1, 10, 37, 75, or 150 mg/m(3) by inhalation, 6 hours per day, 5 days per week, for 16 days. The final mean body weights were similar among exposed and chamber control groups. Compared to chamber controls, the lung weights of males and females exposed to 10 mg/m(3) or greater were increased. Gallium ar senide particles were visible in alveolar spaces and macrophages in some mice exposed to 150 mg/m(3). Moderate proteinosis, mild epithelial hyperplasia, and histiocytic infiltration of the lung were observed in males and females exposed to 10 mg/m(3) or greater. In the larynx, mild squamous metaplasia was seen in mice exposed to 10 mg/m(3) or greater, and mild chronic inflammation occurred in mice exposed to 75 or 150 mg/m(3). 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 1, 10, 37, or 75 mg/m(3), 6 hours per day, 5 days per week, for 14 weeks. All rats survived until the end of the study. The final mean body weight and body weight gain of males exposed to 75 mg/m(3) were significantly less than those of the chamber controls. Hematology and clinical chemistry results indicated that exposure to gallium arsenide induced a microcytic responsive anemia with an erythrocytosis and increased zinc protoporphyrin/heme ratios in exposed groups of rats. There were also increases in platelet and neutrophil counts, a transient decrease in leukocyte counts, and increases in the serum activities of alanine aminotransferase and sorbitol dehydrogenase. These changes were of greater magnitude in male rats. The lung weights of all exposed groups of rats were increased, while testis, cauda epididymis, and epididymis weights of males exposed to 37 or 75 mg/m(3) were generally less than those of chamber controls. Total spermatid heads and spermatid counts were significantly decreased in males exposed to 75 mg/m(3), while epididymal spermatozoa motility was significantly reduced in males ees exposed to 10 mg/m(3) or greater. Gallium arsenide particles were visible in alveolar spaces and macrophages in the lungs of exposed rats. Minimal to marked proteinosis and minimal histiocytic cellular infiltration of the alveoli were observed in all exposed groups; minimal squamous metaplasia in the larynx and lymphoid cell hyperplasia of the mediastinal lymph node were observed in some males and females exposed to 37 or 75 mg/m(3). Exposure-related increases in the incidences of plasma cell hyperplasia of the mandibular lymph node, testicular atrophy, epididymal hypospermia, bone marrow hyperplasia (males), and hemosiderosis in the liver were observed in the 37 and 75 mg/m(3) groups. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 1, 10, 37, or 75 mg/m(3), 6 hours per day, 5 days per week, for 14 weeks. One female mouse exposed to 75 mg/m(3) died before the end of the study. Final mean body weights and body weight gains of males in the 75 mg/m(3) group were signifi cantly less than the chamber controls. Hematology and clinical chemistry results indicated that exposure to gallium arsenide affected the circulating erythroid mass and induced a microcytic responsive anemia with an erythrocytosis and increased zinc protoporphyrin/heme ratios in male and female mice. There were also increases in platelet and neutrophil counts. Compared to the chamber controls, the lung weights of males exposed to 1 mg/m(3) or greater and females exposed to 10 mg/m(3) or greater were increased. Testis, cauda epididymis, and epididymis weights, total spermatid heads, spermatid counts, and concentration and motility of epididymal spermatozoa were generally decreased. Gallium arsenide particles were visible in alveolar spaces and macrophages in the lungs of mice exposed to 1 mg/m(3) or greater. Mild to marked proteinosis, histiocytic infiltration, and epithelial hyperplasia were observed in the alveoli of males and females exposed to 1 mg/m(3) or greater. Minimal to mild suppurative inflammation and granuloma in the lung and squamous metaplasia in the larynx were present in males and females exposed to 10 mg/m(3) or greater. Min imal hyperplasia was observed in the tracheobronchial lymph node of males exposed to 10 mg/m(3) or greater and females exposed to 37 or 75 mg/m(3). Exposure- related increases in the incidences of testicular atrophy, epididymal hypospermia, hematopoietic cell proliferation of the spleen, and hemosiderosis of the liver and spleen were observed in groups of male and female mice exposed to 10 mg/m(3) or greater. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.01, 0.1, or 1.0 mg/m(3), 6 hours per day, 5 days per week, for 105 weeks. Survival and Body Weights: Survival of exposed male and female rats was similar to the chamber controls. Mean body weights of males exposed to 1.0 mg/m(3) were generally less than those of the chamber controls throughout the study; females exposed to 1.0 mg/m(3) had slightly lower mean body weights during the second year. Pathology Findings: Compared to the chamber controls, the incidences of alveolar/bronchiolar neoplasms were significantly increased in females exposed to 1.0 mg/m(3) and exceeded the historical control ranges. Exposure-related nonneoplastic lesions in the lungs of male and female rats included atypical hyperplasia, alveolar epithelial hyperplasia, chronic active inflammation, proteinosis, and alveolar epithelial metaplasia. In the larynx of males exposed to 1.0 mg/m(3), the incidences of hyperplasia, chronic active inflammation, squamous metaplasia, and hyperplasia of the epiglottis were significantly increased. The incidences of benign pheochromocytoma of the adrenal medulla occurred with a positive trend in female rats, and the incidence was significantly increased in the 1.0 mg/m(3) group and exceeded the historical control range. The incidence of mononuclear cell leukemia was significantly increased in females exposed to 1.0 mg/m(3) and exceeded the historical control range. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 0.5, or 1.0 mg/m(3), 6 hours per day, 5 days per week, for 105 (males) or 106 (females) weeks. Survival and Body Weights: Survival of male and female mice was similar to the chamber controls. Mean body weights of exposed groups of males were similar to those of the chamber controls throughout the study; mean body weights of exposed groups of females were greater than those of the chamber controls from week 13 until the end of the study. Pathology Findings: Exposure-related nonneoplastic lesions in the lung of all groups of exposed mice included suppurative focal inflammation, chronic focal inflammation, histiocyte cellular infiltration, alveolar epithelial hyperplasia, and proteinosis. Increased incidences of minimal lymphoid hyperplasia of the tracheobronchial lymph node occurred in mice exposed to 1.0 mg/m(3) and in 0.5 mg/m(3)mg/m(3) males. GENETIC TOXICOLOGY: Gallium arsenide was not mutagenic in several strains of Salmonella typhimurium, with or without S9 metabolic activation enzymes, and no increase in the frequency of micronucleated erythrocytes was observed in peripheral blood of male or female mice exposed to gallium arsenide by inhalation for 14 weeks. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was no evidence of carcinogenic activity of gallium arsenide in male F344/N rats exposed to 0.01, 0.1, or 1.0 mg/m(3). There was clear evidence of carcinogenic activity in female F344/N rats based on increased incidences of benign and malignant neoplasms in the lung. Increased incidences of benign neoplasms of the adrenal medulla and increased incidences of mononuclear cell leukemia were also considered to be exposure related. There was no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to 0.1, 0.5, or 1.0 mg/m(3). Exposure to gallium arsenide caused a spectrum of nonneoplastic lesions in the lung of rats and mice, the larynx of male rats and hyperplasia of the tracheobronchial lymph node in mice. Synonym: Gallium monoarsenide.
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PMID:NTP Toxicology and Carcinogenesis Studies of Gallium Arsenide (CAS No. 1303-00-0) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). 1256 48

Isobutyraldehyde, a branched alkyl aldehyde, is used as a chemical intermediate and flavoring agent. It was nominated by the National Cancer Institute for toxicity and carcinogenicity studies by the NTP. Reasons for nomination and selection of isobutyraldehyde for study included its high potential for human exposure as suggested by its high production volume, its use as a chemical intermediate and food flavoring agent, suspicion of carcinogenicity due to an increased incidence of cancer at an aldehyde manufacturing plant where workers were exposed to a variety of aldehydes, its structural relationship to formaldehyde (a nasal carcinogen in rats), and the lack of toxicity and carcinogenicity studies on isobutyraldehyde in animals. Although human exposure occurs orally, dermally, or via inhalation, the inhalation route of exposure was selected for these animal studies because of the instability of isobutyraldehyde in water and feed. Male and female F344/N rats and B6C3F1 mice were exposed to isobutyraldehyde (approximately 99% pure) by inhalation for 13 weeks or 2 years. Genetic toxicology studies were conducted in vitro in Salmonella typhimurium, L5178Y mouse lymphoma cells, and cultured Chinese hamster ovary cells; in vivo tests were conducted in Drosophila melanogaster germ cells and bone marrow cells of rats and mice. 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were exposed to 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm isobutyraldehyde by inhalation, 6 hours per day, 5 days a week, for 13 weeks. All rats exposed to 8,000 ppm died before the end of the study. Three male rats and six female rats in the 4,000 ppm groups and one female in the 500 ppm group died before the end of the study. The final mean body weight of male rats in the 4,000 ppm group and the body weight gains of 4,000 ppm males and females were significantly less than those of the chamber controls. Clinical findings in rats exposed to 4,000 or 8,000 ppm included abnormal respiratory sounds, decreased activity, nasal discharge, prostration, and slowed respiration. A minimal mature neutrophilia, evidenced by increased segmented neutrophil numbers, occurred in exposed groups of male and female rats. Exposure to isobutyraldehyde resulted in minimal increases in alanine aminotransferase activity in all groups of male and female rats. Spermatozoal motility in 500 and 1,000 ppm males was significantly reduced and females exposed to 4,000 ppm differed significantly from the chamber control females in the relative time spent in the estrous stages. No gross lesions were observed at necropsy that could be associated with isobutyraldehyde exposure. In the 8,000 ppm groups, severe necrosis of the epithelium, and occasionally of the entire mucosa, of the nasal turbinates accompanied by an acute inflammatory reaction was observed. Increased incidences of squamous metaplasia and mild acute inflammation occurred in male and female rats exposed to 4,000 ppm. Minimal to mild degeneration of the olfactory epithelium was observed in all male rats in the 2,000 and 4,000 ppm groups. Male rats exposed to 4,000 or 8,000 ppm and females exposed to 4,000 ppm had mild osteodystrophy of the turbinate bone. The incidences of necrosis/degeneration of the larynx and trachea were increased in male rats in the 8,000 ppm group. The incidences of mild to moderate lymphoid depletion of the spleen and thymus and lymphoid necrosis of the thymus were significantly increased in male and female rats exposed to 8,000 ppm. 13-WEEK STUDY IN MICE: Ten male and 10 female B6C3F1 mice were exposed to 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm isobutyraldehyde by inhalation, 6 hours per day, 5 days per week, for 13 weeks. One male in the chamber control group, one male in the 1,000 ppm group, nine males and all females in the 4,000 ppm groups, and all males and females in the 8,000 ppm groups died before the end of the study. The final mean body weight and body weight gain of female mice in the 1,000 ppm group were significantly less than those of the chamber controls. Clinical findal findings included decreased activity, tremors, prostration, and slower and labored respiration. The absolute and relative kidney weights of males in the 1,000 and 2,000 ppm groups were significantly increased. There were no gross lesions observed at necropsy that could be associated with isobutyraldehyde exposure. Histopathologically, the nasal cavity and lymphopoietic tissues were considered target organs, with changes similar, but not identical, to those observed in rats. Increased incidences of nonneoplastic lesions of the nasal cavity were observed in male and female mice exposed to 1,000 ppm or greater. These lesions included necrosis, inflammation, hyperplasia, and squamous metaplasia of the epithelium; serous and suppurative exudate within the nasal passages; olfactory epithelial degeneration; and osteodystrophy of the turbinate bone. Mild to moderate lymphoid depletion and/or lymphoid necrosis were observed in the thymus of male and female mice exposed to 8,000 ppm. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female F344/N rats were exposed to 0, 500, 1,000, or 2,000 ppm isobutyraldehyde by inhalation, 6 hours per day, 5 days per week, for 105 weeks Survival, Body Weights, and Clinical Findings No differences in survival rates between exposed and chamber control rats were found. The mean body weights of male and female rats were generally similar to those of the chamber controls throughout the study. Pathology Findings No increase in neoplasm incidences that could be attributed to exposure to isobutyraldehyde was observed in male or female rats. Nonneoplastic lesions related to isobutyraldehyde exposure were limited to the nose and consisted of squamous metaplasia of the respiratory epithelium, degeneration of the olfactory epithelium, and suppurative inflammation. Incidences of minimal to mild squamous metaplasia in 1,000 and 2,000 ppm males and females and in 500 ppm females were significantly greater than those in the chamber controls. Another lesion associated with isobutyraldehyde exposure was minimal to mild degeneration of the olfactory epithelium in 2,000 ppm males and females. The incidences of suppurative inflammation (rhinitis) in male and female rats exposed to 2,000 ppm were increased compared to the chamber controls. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female B6C3F1 mice were exposed to 0, 500, 1,000, or 2,000 ppm isobutyraldehyde by inhalation, 6 hours per day, 5 days per week, for 105 weeks. Survival, Body Weights, and Clinical Findings There was an exposure-related decrease in survival of male mice, and the survival of males exposed to 2,000 ppm was marginally lower than that of the chamber controls. The mean body weights of female mice exposed to 1,000 or 2,000 ppm were lower than those of the chamber controls during the second year of the study. Pathology Findings No neoplasms that could be attributed to iso butyraldehyde exposure were observed in mice. Non neoplastic lesions related to isobutyraldehyde exposure were limited to the nose. The incidences of olfactory epithelial degeneration in 1,000 and 2,000 ppm males and females were significantly greater than in the chamber controls. GENETIC TOXICOLOGY: Isobutyraldehyde is mutagenic in vitro and in vivo, with the strongest responses observed in mammalian cell assays that measured chromosomal damage. Results of an initial mutagenicity test in S. typhimurium were negative; a second test, con ducted with different strains and varying concentrations of induced S9 activation enzymes, gave equivocal results. Strongly positive responses were obtained in the mouse lymphoma assay for mutation induction in L5178Y cells without S9 and in cytogenetic tests for induction of sister chromatid exchanges and chromosomal aberrations in cultured Chinese hamster ovary cells. Sister chromatid exchanges were significantly increased with and without S9, but induction of chromosomal aberrations was noted unequivocally only in the absence of S9. No induction of sex-linked recessive lethal mutations was observed in germ cells of male D. melanogaster administered isobutyraldehyde by feeding or by injection. In vivo, isobutyraldehyde was demonstrated to induce chromosomal aberrations in bone marrow cells of male mice, but no increases in micronuclei were observed in bone marrow cells of mice or rats after administration of isobutyraldehyde. All these in vivo cytogenetic studies used doses that reached lethality CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was no evidence of carcinogenic activity of isobutyraldehyde in male or female F344/N rats or male or female B6C3F1 mice exposed to 500, 1,000, or 2,000 ppm isobutyraldehyde. In male and female rats, exposure to isobutyraldehyde induced squamous metaplasia and suppurative inflammation of the nasal respiratory epithelium and degeneration of the nasal olfactory epithelium. In male and female mice, exposure to isobutyraldehyde caused degeneration of the nasal olfactory epithelium. Synonyms: Dimethylacetaldehyde; 2-formylpropane; isobutanal; isobutylcarboxaldehyde; isobutyral; isobutyric aldehyde; isobutyrylaldehyde; isopropylformaldehyde; 2-methylpropanal; 2-methyl-1-propanal; a-methylpropionaldehyde; 2-methylpropionaldehyde; valine aldehyde
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PMID:NTP Toxicology and Carcinogenesis Studies of Isobutyraldehyde (CAS No. 78-84-2) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). 1257 1

Cytotoxic T lymphocytes (CTL) and Kupffer cells play an important role in the immune control of hepatitis B virus (HBV), but may also induce liver injury during infection. We investigated the intrahepatic immune response in liver biopsies of chronic HBV patients in relation to inflammatory liver injury and viral control. Forty-seven liver biopsies from patients with chronic HBV with varying degrees of inflammation (ALT values) were selected. Acute hepatitis and normal liver specimens served as controls. Immune effector cells, cytotoxic effector molecules and cytokine producing cells were quantified after immunohistochemical staining in lobular and portal areas of the biopsies. The intralobular number of CD8+ T-lymphocytes was significantly decreased in biopsies of patients with high ALT (r = -0.54; P < 0.001). Higher ALT-values were correlated with increased numbers of granzyme+ cells in portal areas (r = 0.65; P < 0.001) and higher numbers of intralobular Fas-L+ cells (r = 0.32; P = 0.05). Fas-L was expressed on Kupffer and lymphoid cells. More intralobular CD8+ T-lymphocytes were found in HBeAg- than in HBeAg+ patients (P = 0.002). But IFN-gamma and TNF-alpha producing cells were observed sporadically in chronic HBV patients. Hence, in chronic HBV infection, low viral replication and HBeAg negativity is related to increased presence of intralobular CD8+ T-lymphocytes. Persistence of the virus may be caused by the absence of cells producing anti-viral cytokines in the liver. Inflammatory liver injury during chronic HBV infection is probably not the result of increased numbers of infiltrating CD8+ T-lymphocytes, but of Fas-L expression by Kupffer cells and increased cytolytic activity of cells in portal areas.
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PMID:The role of intrahepatic immune effector cells in inflammatory liver injury and viral control during chronic hepatitis B infection. 1275 33

We reported a case of non-Hodgkin's lymphoma where liver involvement was the predominant clinical manifestation. A 27-year old man presented with markedly elevated serum aspartate aminotrasferase, alanine aminotransferase and lactate dehydrogenase, reduced prothrombin activity, thrombocytopenic purpura and hepato-splenomegaly without adenopathy. Viral, toxic, autoimmune and metabolic liver diseases were excluded. Bone marrow biopsy showed an intracapillary infiltration of T-lymphocytes with no evidence of lipid storage disease. Because of a progressive spleen enlargement, splenectomy was performed. Histological examination showed lymphomatous intrasinuses invasion of the spleen. Immunohistochemical investigation revealed the T phenotype of the neoplastic cells: CD45+, CD45RO+, CD3+, CD4-, CD8-, TIA1-. About 50 % of the lymphoid cells expressed CD56 antigen. The diagnosis of hepatosplenic T cell lymphoma was done. The patient was treated with chemotherapy, which induced a complete remission. Eighteen months later, he had a first relapse with increased aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, thrombocytopenic purpura and blast in the peripheral blood. In spite of autologous bone marrow transplantation, he died twenty months after the diagnosis. Even in the absence of a mass lesion or lymphoadenopathy, hepatosplenic T-cell lymphoma should be considered in the differential diagnosis of a patient whose clinical course is atypical for acute hepatic dysfunction.
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PMID:Hepato-splenic lymphoma: a rare entity mimicking acute hepatitis: a case report. 1280 Feb 62

In recent years preclinical and clinical studies have been undertaken with selected monoclonal antibodies (MoAbs) either alone or coniugated to toxins in patients with several lymphoid malignancies, including chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL) and hairy cell leukemia (HCL). Two MoAbs, directed against CD20 antigen (Rituximab, RIT) and CD52 antigen (Campath-1H, alemtuzumab, ALT) demonstrate significant activity in CLL. The most notable success to data has been achieved with ALT, both in previously treated and untreated patients with CLL. ALT is a humanized rat IgG1 antibody that binds to the cell membrane of virtually all normal as well as malignant lymphocytes. In the vast majority of CLL patients ALT causes constant reduction of abnormal blood lymphocytes, usually in less than 4 weeks, and disappearance of CD5/CD19 co-expression cells from blood. The regression of lymphoid infiltration from other sites is less clear. ALT is also highly active in patients with CLL in progression, even refractory to fludarabine (FA). Hematological toxicity, especially long-lasting lymphocytopenia, was noted in the majority of patients. The most important clinical side effects of ALT treatment were infections, mainly herpes simplex virus and cytomegalovirus reactivation. RIT is also active in CLL in conventional doses. However some studies suggest that higher doses are more effective than standard doses, used routinely in other lymphoid malignancies. The activity of ALT and RIT in CLL patients resistant to FA and their synergistic interactions with cytotoxic drugs suggests that a combination of these agents may lead to further progress in the treatment of this disease. The T-cell variant of PLL has demonstrated impressive responses to ALT in several trials even if the patients were refractory to deoxycoformycin (DCF) and other agents. However, this MoAb is not curative, because all patients eventually relapsed. Consequently, treatment with ALT may need to be associated with stem cell transplantation to consolidate and maintain long-term remissions. Recently anti-CD22 and anti-CD25 immunotoxins have been investigated in purine analogues refractory or relapsed HCL. The presented results indicate that these agents are highly active and well tolerated even if the patients were resistant to 2-CdA or DCF.
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PMID:Monoclonal antibodies in the treatment of chronic lymphoid leukemias. 1510 4

Ginsan, a polysaccharide isolated from Panax ginseng, has been shown to be a potent immunomodulator, producing a variety of cytokines such as TNF-alpha, IL-1, IL-2, IL-6, IL-12, IFN-gamma and GM-CSF, and stimulating lymphoid cells to proliferate. In the present study, we analyzed some immune functions 1st-5th days after ginsan i.p. injection, including the level of non-protein thiols (NPSH) as antioxidants, heme oxygenase (HO) activity as a marker of oxidative stress, zoxazolamine-induced paralysis time and level of hepatic cytochrome P-450 (CYP450) as indices of drug metabolism system, and activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and albumin level as indicators of hepatotoxicity. Ginsan in the dose of 100 mg/kg caused marked elevation (1.7 to approximately 2 fold) of HO activity, decrease of total CYP450 level (by 20-34%), and prolongation of zoxazolamine-induced paralysis time (by 65-70%), and showed some differences between male and female mice. Ginsan treatment did not seem to cause hepatic injury, since serum AST, ALT, and ALP activities and levels of total bilirubin and albumin were not changed.
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PMID:Effects of polysaccharide ginsan from Panax ginseng on liver function. 1520 59

We examined hepatitis C virus (HCV) RNA levels in serum, peripheral blood mononuclear cells (PBMC), and the liver for 135 patients with chronic HCV infections, 44 of whom were human immunodeficiency virus (HIV) positive and treated with highly active antiretroviral therapy (group A), 66 of whom were HIV negative (group B), with abnormal serum alanine aminotransferase (ALT) values, and 25 of whom were HIV negative, with ALT values of </=1.5 times the normal value (group C). Patients had not been treated with interferon, with or without ribavirin, at the time of the study. A statistically significant correlation between HCV RNA levels in the liver and serum was reproducibly documented, whereas this was inconsistent for serum and PBMC. A comparative evaluation of HCV RNA levels in the liver and PBMC showed significantly lower values for group A than for groups B and C (P < 0.01 and P < 0.0001, respectively). In contrast, HCV RNA levels in serum were significantly higher for group A than for group B (P < 0.001). A dissociation between HCV RNA levels in serum and the liver was found for patients with HIV-HCV coinfections. Although the relative contribution of extrahepatic reservoirs, including lymphoid cells, to HCV RNA levels in serum is unclear, it may be speculated that a low intrahepatic HCV burden is caused by restored immunocompetence after successful antiretroviral therapy in coinfected patients.
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PMID:Dissociation of serum and liver hepatitis C virus RNA levels in patients coinfected with human immunodeficiency virus and treated with antiretroviral drugs. 1524 52

The behavior of hepatitis C in states of immunodeficiency is poorly understood and it is still unclear whether the characteristics of hepatitis C virus (HCV) infection in renal transplant patients differ from those observed in immunocompetent subjects. The aim of this study was to compare the biochemical and histologic characteristics of chronic HCV infection between renal transplant and immunocompetent patients. Forty-one HCV-RNA-positive renal transplant patients and 41 immunocompetent controls matched for gender, age at infection and time of infection were included in the study. The groups were compared regarding laboratory and histologic variables. Renal transplant patients showed lower alanine aminotransferase (ALT) levels (p = 0.005) and higher levels of gamma-glutamyltransferase (p = 0.003), alkaline phosphatase (p < 0.001), and direct bilirubin (p < 0.001) when compared with controls. Histologic analysis revealed less intense portal (p < 0.001) and periportal (p = 0.046) inflammatory infiltrate in renal transplant patients but a larger proportion of cases with confluent necrosis (p = 0.043). No difference in the presence of septal fibrosis, hepatic steatosis, bile duct injury and siderosis was observed. However, there was a difference in the presence of lymphoid aggregates, which were less frequent in the renal transplant group (p < 0.001). In conclusion, the characteristics of hepatitis C in renal transplant patients differ from that observed in immunocompetent patients. In renal transplant patients, HCV infection is biochemically characterized by lower ALT levels and higher frequency of cholestasis. Regarding histology, despite lower frequency of lymphoid aggregates and less intense portal/periportal inflammatory infiltrate, a greater lobular damage was observed. The impact of these differences on the progression of fibrosis remains to be established.
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PMID:Hepatitis C virus infection in renal transplant patients: a comparative study with immunocompetent patients. 1631 22


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