Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2-Acetyl-4-tetrahydroxybutyl imidazole (THI), a component of the food colouring ammonia caramel, has been shown to produce a profound and rapid lymphopenia in peripheral blood in the rat. In order to investigate whether the cause of the lymphopenia was due to the reduced production and influx in the circulation, redistribution of lymphocytes into other lymphoid compartments or an increased cell death, THI (1 mg/kg/day) was given in the drinking water for up to 14 days to F344 rats. A profound depletion of lymphocytes after already 1 day was only found in the blood compartment, whereas no such marked and rapid changes were found in the cellularity of other lymphoid compartments. The proportion and absolute number of DNA-synthesizing cells in each lymphoid organ was quantified using an antibody directed against incorporated 5-bromo-2'-deoxyuridine (BrdU), 1 h after a single BrdU injection. Additionally, enumeration and localization of BrdU+ cells was determined at later time points after a single BrdU injection by flow cytometry and immunocytochemistry, in order to examine the distribution and localization of recently formed (BrdU+) lymphocytes. THI treatment had no effect on the proliferation rate and the distribution of newly formed (BrdU+) cells in the lymphoid organs. However, migration studies revealed that THI treatment resulted in an increased percentage of fluorescein-labelled peripheral blood lymphocytes found in the spleen and bone marrow and a decreased percentage in the cervical and mesenteric lymph nodes, 24 h after injection. Collectively these results indicate that the lymphopenia in the peripheral blood compartment after THI treatment, is caused by a rapid sequestration of lymphocytes into the spleen and bone marrow rather than by a reduced lymphocyte production and release into the periphery. The fact that THI also caused lymphopenia in splenectomized rats, indicates that the spleen does not play an active part in the change in migrational behaviour of lymphocytes after THI treatment. Finally, as there was no increase in the absolute number of lymphocytes found in the spleen or bone marrow it seems they are rapidly degraded.
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PMID:The role of lymphocyte production and migration in the lymphopenia caused by 2-acetyl-4-tetrahydroxybutyl imidazole. 152 36

THI is a component of ammonia caramel, a widely used food colouring. The effect of THI on the immune system has been determined in the male F344 rat. THI was given in the drinking water at doses of 1, 10 and 50 mg/l (equivalent to 0.1, 1 and 5 mg/kg per day) to animals on a vitamin B6-deficient diet. After 1 week, the immune competence of the animals was assessed under continued THI treatment. No marked changes in thymus or spleen weight were observed after THI treatment, although there was an increased number of pyknotic cells in the thymic cortex, mainly engulfed by macrophages and there appeared to be a slight thinning of the cortex area. THI produced a significant loss in T and B lymphocytes in peripheral blood but not in the spleen. No change in natural killer (NK) cell activity against YAC-1 target cells was observed in the spleen. The observed increase in NK cell activity in peripheral blood was due to an increase in circulating large granular lymphocytes (LGL). Although the serum antibody titre against keyhole limpet haemocyanin (KLH) was not affected by THI treatment, B cells showed less proliferation when cultured with lipopolysaccharide. T cell function was impeded as measured in mitogen-induced proliferation assay, delayed-type hypersensitivity assay and host versus graft (popliteal lymph node) assay. The results indicate that THI is an immunosuppressor in the rat, in whom it can produce profound lymphopenia and suppression of cell-mediated immunity.
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PMID:Immunosuppressive effects of 2-acetyl-4-tetrahydroxybutyl imidazole (THI) in the rat. 186 15

Amanita phalloides mushroom poisoning is an increasingly common and potentially lethal problem for which liver transplantation offers definitive therapy in selected patients. When significant liver dysfunction appears, early transfer to a liver transplant center is important to identify appropriate candidates and to begin the search for a donor organ. The clinical course of five severely poisoned patients, four of whom underwent liver transplantation, is reviewed. Indications for transplantation included primarily a markedly prolonged prothrombin time that was only partially correctable and a constellation of findings including metabolic acidosis, hypoglycemia, hypofibrinogenemia, and increased serum ammonia, following a marked elevation in serum aminotransferase levels. Unlike viral fulminant hepatic failure, grade III or IV hepatic encephalopathy, marked elevation of the serum bilirubin level, and azotemia were not indications for transplantation. Resected livers demonstrated hepatocyte viability of 0% to 30%. Manifestations of Amanita poisoning complicating preoperative and/or postoperative care included severe diarrhea, gastrointestinal hemorrhage, hypophosphatemia, bowel edema, and marrow suppression with lymphopenia, thrombocytopenia, and neutropenia. All five patients are well 1 year later. This largest experience with liver transplantation for Amanita poisoning further defines the early clinical and laboratory indications for, and the unique complicating features of, transplantation in this setting.
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PMID:Liver transplantation for severe Amanita phalloides mushroom poisoning. 233 13

The ability of B6 vitamers to prevent the lymphopenic effects of ammonia caramel fed to rats has been evaluated. Diets containing 10 ppm pyridoxine or pyridoxal prevented the lymphopenia produced in rats consuming an 8% (w/v) solution of ammonia caramel, whereas the dietary content of pyridoxamine needed to be increased to 20 ppm to have the same effect. In contrast to the results of the enteral administration of the individual B6 vitamers, pyridoxamine was found to be the most effective vitamer in preventing the ammonia caramel-induced lymphopenia when administered parenterally. However, all the nutritionally active forms of vitamin B6 were able to prevent the depression of the peripheral blood lymphocyte count, which resulted from ingestion of ammonia caramel by rats. The proposal that oral administration of pyridoxine may prevent the intestinal absorption of the lymphopenic constituent of ammonia caramel, 2-acetyl-4(5)-(1,2,3,4-tetrahydroxy)butylimidazole (THI), is discredited, since THI was found to reduce the lymphocyte count after parenteral administration in rats fed 0.04 ppm pyridoxone in the diet and that increased amounts of dietary pyridoxine (10 ppm) could still prevent this effect. These findings further emphasise the important relationship between dietary vitamin B6 content and the lymphopenic effects of ammonia caramel/THI in the rat.
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PMID:Effect of oral and parenteral administration of B6 vitamers on the lymphopenia produced by feeding ammonia caramel or 2-acetyl-4(5)-(1,2,3,4-tetrahydroxy)butylimidazole to rats. 260 99

A derivative of ammonia caramel colour (AC) is known to induce a selective lymphopenia in rats. Accordingly, the haematological effects were studied in mice of oral administration in drinking water of 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI), the component of AC responsible for lymphopenia. Initially five groups of BALB/c mice (five mice per group) were given doses of THI ranging from 0 to 200 parts/10(6) and bled weekly. Doses of THI from 5 to 100 parts/10(6) had no effect on circulating leucocytes over 6 weeks, but lymphopenia occurred with 200 parts/10(6). An increase in the concentration of THI to 400 parts/10(6) in the group on the lowest dose resulted in lymphopenia. An increase in dosage in two groups of mice, to 1000 and 2000 parts/10(6), resulted in marked lymphopenia. The number of neutrophils, eosinophils and monocytes remained unchanged throughout the experiment. Measurement of the proportions of CD4(L3T4)+ and CD8(Ly2)+ lymphocytes in lymph nodes from mice on high doses of THI did not show a selective depression of either subset, although both were increased relative to non-T cells. THI causes a selective lymphopenia in mice, as in rats, but at relatively higher doses, and merits investigation in mice as an experimental treatment for states of lymphocyte excess or overactivity.
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PMID:Lymphopenic effects on mice of a component of ammonia caramel, 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI). 314 40

Evidence exists implicating the epidermal ultraviolet B (UVB) photoproduct cis-urocanic acid as an immunogenic mediator of the systemic suppression of T cell-mediated immunity by UVB exposure. Cis-urocanic acid appears to act via histamine receptor pathways, and histamine receptor antagonists and other imidazole ring compounds may modify its immune suppressing action. A component of the food coloring substance ammonia caramel, 2-acetyl-4-tetrahydroxybutylimidazole (THI), which is known to cause lymphopenia in rats, appears to suppress immunity by a similar pathway when the contact hypersensitivity reaction has been the immune function assay in mice. The induction of lymphopenia in rats by THI is inhibited by the vitamin pyridoxine. This study demonstrates that the suppression of contact hypersensitivity in mice by UVB radiation, cis-urocanic acid, or THI is strongly inhibited by supplemental pyridoxine, fed at 30 mg/kg diet, in comparison with the normal diet, which supplies 7 mg pyridoxine/kg diet. These results suggest that pyridoxine competes with cis-urocanic acid and THI for the same binding site or receptor, which we postulate to be a histamine-like T lymphocyte receptor, and that a role may exist for the control of photoimmunosuppression by this vitamin.
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PMID:Pyridoxine supplementation protects mice from suppression of contact hypersensitivity induced by 2-acetyl-4-tetrahydroxybutylimidazole (THI), ultraviolet B radiation (280-320 nm), or cis-urocanic acid. 787 21

The compound 2-acetyl-4-tetrahydroxybutylimidazole (THI), a component of ammonia caramel, has been shown to cause lymphopenia and to impair several immune functions in rats and mice. In this study we show that THI effectively suppresses contact hypersensitivity dose responsively in the hairless mouse, whether administered topically or orally. The suppression was shown to be prevented by topical administration of the histamine antagonist, cimetidine, and by the dipeptide, carnosine. Splenocytes from THI-treated mice failed to elicit normal contact hypersensitivity when transferred to naive mice. This suggests that THI acts by modifying splenocyte function, perhaps via a histamine-like receptor site(s).
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PMID:Suppressive effect of 2-acetyl-4-tetrahydroxybutylimidazole on contact hypersensitivity in the Skh: HR hairless mouse. 840 Aug 81

A 6-day-old, female roan antelope (Hippotragus equinus cottoni) was diagnosed with a single intrahepatic portosystemic venous shunt at necropsy. Clinical signs had included weakness, lethargy, hypothermia, diarrhea, and a weak suckle response. Multiple seizure episodes were associated with hypoglycemia and characterized by vocalization, muscle fasciculations, and disorientation. Hematologic abnormalities included anemia with hypochromasia, anisocytosis, poikilocytosis, and leukopenia with neutropenia and lymphopenia. Serum biochemical abnormalities included elevations in blood urea nitrogen and total serum bile acid concentration. A portosystemic vascular anomaly should be a differential diagnosis for nonthriving, exotic ruminant calves with overt or subtle neurologic signs, persistent hypoglycemia, and/or elevated bile acids. In very young calves, total bile acid concentration may be more useful in establishing a diagnosis than blood ammonia concentration.
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PMID:Intrahepatic portosystemic venous shunt in a neonatal roan antelope (Hippotragus equinus cottoni). 1731 83