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)

Intravenous potentiated anesthesia was made with six clinically normal boars of the White Bulgarian breed, weighing 50 kg, premedication of Atropini sulfas (50 gamma/kg M., s/c) and of a mixture of Droperidol (0.25 mg/kg M.) and Fentanyl (0.05 mg/kg M.) introduced via Sinus venosus ophthalmicus being administered 15 min. prior to 13 mg/kg M. of 5% water solution of thiopental-sodium injected in the same sinus. Prior to and following anesthesia at the 1st, 3rd, and 24th hour and on the 4th and 7th day the blood was checked with regard to hemoglobin, erythrocytes, erythrocyte sedimentation rate, hematocrit, leukocytes and leukocyte formula, total protein and protein fractions, calcium, phosphorus, magnesium, sodium, potassium, chlorides, total and direct bilirubin, and fibrinogen. Hemoglobin, erythrocytes, and hematocrit were found to drop insignificantly mathematically. The rate of increase of the sedimentation did not fully correspond to the drop of the erythrocyte count. The increase in leukocytes was accompanied by transient neutrophilia, eosinopenia, and lymphopenia in the early hours following anesthesia. The changes in the total protein and protein fractions, fibrinogen, total and direct bilirubin, and the other element indices referred to were shown to be close to the physiologic levels.
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PMID:[Hematologic and biochemical changes in the blood of boars undergoing potentiated anesthesia with droperidol, fentanyl and thiopental]. 378 57

Nitrogen balance in six obese adolescent boys and three obese girls was studied during two nonconsecutive three-week dietary periods. Protein intake was based on an ideal body weight calculated from the measurement of total body water. The diets consisted of 1.5 gm meat protein/kg IBW/day plus 1.0 gm glucose/kg IBW/day, or an isonitrogenous diet made isocaloric with fat. Each dietary period was preceded by a controlled five-day diet designed to achieve weight maintenance. The first dietary period was followed by a one-month period of re-equilibration. The addition of carbohydrate to protein produced a significantly better cumulative nitrogen balance than P + F. Significant nitrogen losses persisted throughout the entire dietary period of P + F in three patients, but were observed in only one patient during P + G. Lymphopenia occurred in one subject on P + F but did not occur during P + G. Serum albumin concentrations were unchanged on both diets. Transferrin values decreased during P + F, but did not differ significantly from prediet levels during P + G. However, the observation of prolonged nitrogen losses in one subject on P + G and the limited experience with highly restrictive diets in obese adolescents emphasize that such diets must be used with caution and monitored carefully.
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PMID:Optimal dietary therapy for obese adolescents: comparison of protein plus glucose and protein plus fat. 706 18

Administration of Caramel Colour III is associated with lymphopenia in laboratory animals, especially if the animals are fed a vitamin B6-deficient diet. Recently, functional immunological alterations in rats exposed to Caramel Colour III have been reported. The component of Caramel Colour III that is responsible for the immunological effects has been shown to be 2-acetyl-4-tetrahydroxybutyl imidazole (THI). In the present study, female Balb/c mice fed a diet with a relatively high vitamin B6 content were exposed to 2 or 10% of a commercial Caramel Colour III preparation with a low THI content (less than 25 ppm) in the drinking water for 9 wk. Although this treatment did not induce a lymphopenia in the exposed mice, flow cytometric analysis of lymphocyte subpopulations demonstrated reductions in the CD4+ and CD8+ cell populations. In addition, the proliferative response of spleen cells to B and T cell mitogens was significantly reduced in the mice exposed to 2% Caramel Colour III. No changes were observed in natural killer cell activity or in the humoral antibody response to a viral antigen. The results indicate that Caramel Colour III that meets the specified limit of less than 25 mg THI/kg may, nevertheless, interfere with the lymphoid system in mice with an adequate vitamin B6 status.
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PMID:Effects of subchronic exposure to Caramel Colour III on the immune system in mice. 813 68

Administration of the color additive caramel color III (AC) may cause a reduction in total white blood cell counts in rats due to reduced lymphocyte counts. Beside lymphopenia, several other effects in rat have been described. The effects are caused by the imidazole derivative 2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole (THI) and occur in rats fed a diet low in vitamin B6. In the present paper, immune function studies on AC and THI with rats fed a diet low, but not deficient in vitamin B6 are presented and discussed. Rats were exposed to 0.4 or 4% AC or to 5.72 ppm THI in drinking water during and for 28 days prior to the start of immune function assays. Resistance to Trichinella spiralis was examined in an oral infection model and clearance of Listeria monocytogenes upon an intravenous infection was studied. In addition, natural cell-mediated cytotoxicity of splenic and nonadherent peritoneal cells and the antibody response to sheep red blood cells were studied. From the results it is concluded that exposure of rats to AC or THI influenced various immune function parameters. Thymus-dependent immunity was suppressed, while parameters of the nonspecific resistance were also affected, as shown by a decreased natural cell-mediated cytotoxicity in the spleen and an enhanced clearance of L. monocytogenes.
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PMID:Immunotoxic effects of the color additive caramel color III: immune function studies in rats. 843 26

2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole (THI) is an immunosuppressive component of caramel food colouring that causes lymphopenia in mice and rats by an unknown mechanism. In this study we investigated some of the affects of THI on the murine immune system. Initially we showed that splenic T lymphocytes from mice treated with 50 mg/l THI in their drinking water were unable to launch a mixed lymphocyte reaction (MLR) against allogeneic stimulator cells, and had decreased and delayed interleukin-2 (IL-2) production. However, these T cells exhibited a normal proliferative response to concanavalin A (Con A), immobilized anti-CD3 monoclonal antibody (mAb) and anti-CD3 plus anti-CD28 mAb. Furthermore, the MLR response could be restored by the addition of IL-2 to the MLR culture. Homing studies using intravenous injection of fluorescence-labelled splenocytes showed that THI treatment decreased absolute numbers of labelled T and B lymphocytes in the blood and the spleen. Furthermore, these labelled cells reappeared in the blood and the spleen when mice were taken off THI, indicating that lymphocyte recirculation and splenic homing were modified reversibly by THI treatment. Cessation of THI treatment also resulted in a rapid reappearance of MLR responsiveness in the spleen, indicating that THI treatment does not functionally impair recirculating T cells. Collectively these data are compatible with the concept that a rapidly recirculating population of T cells, which produce IL-2 in an allogeneic MLR, are lost from the blood and spleen following THI treatment, and are sequestered in other, yet to be identified, tissues.
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PMID:The immunosuppressive compound 2-acetyl-4-tetrahydroxybutyl imidazole inhibits the allogeneic mixed lymphocyte reaction by sequestration of a recirculating subpopulation of T cells. 866 39

Recently, the synthetic immunomodulator Linomide (quinoline-3-carboxamide, LS 2616) was reported to prevent IDDM and insulitis in NOD mice. The mechanism for this protective effect is not known. The cytokine interleukin 1 (IL-1) may be a pathogenetic factor in the initial destruction of the beta-cells leading to IDDM. This study was undertaken to investigate the influence of Linomide on IL-1beta induced diabetogenic and hormonal changes in the rat in vivo, and on IL-1beta mediated synthesis of NO and inhibition of insulin secretion in isolated islets of Langerhans ex vivo. Normal male Wistar Kyoto rats received 4.0 microg/kg of recombinant human IL-1beta (rhIL-1beta) i.p. daily for 5 days with or without Linomide (8-9 mg/kg/day) in the drinking water. Litters of neonatal Wistar rats were pretreated for 3 days with injections of 10 mg/kg of Linomide i.p., and pancreatic islets of Langerhans were isolated for ex vivo studies. Linomide alone caused significant hypercorticosteronemia, hypoglucagonemia, lymphopenia and neutrophilia. Linomide had no effect on IL-1beta induced hyperglycemia, hyperglucagonemia, lymphopenia, neutrocytosis, or hypercorticosteronemia on day three and hypocorticosteronemia on day five. Further, Linomide did not prevent rhIL-1beta mediated reduction in insulin secretion or increase in NO synthesis ex vivo. In conclusion, Linomide does not seem to exert its protective effect on IDDM development via inhibition of interleukin 1 action on islet insulin release or NO production, but the increase in plasma corticosterone may contribute to the understanding of the immunomodulatory effects of Linomide.
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PMID:Linomide increases plasma corticosterone in normal rats, but does not prevent the inhibitory action of IL-1 on beta-cells in vivo or ex vivo. 891 32

Purine nucleoside phosphorylase deficiency leads to a dGTP-mediated T-lymphopenia, suggesting that an analogue of deoxyguanosine would be selectively effective in T-cell disease. 9-beta-D-Arabinofuranosylguanine (ara-G) is relatively resistant to hydrolysis by purine nucleoside phosphorylase and selectively toxic to T cells, but its low solubility has prevented its use in the clinic. 2-Amino-6-methoxy-arabinofuranosylpurine (GW506U) serves as the water-soluble prodrug for ara-G. A Phase I trial in patients with refractory hematological malignancies demonstrated that the clinical responses to this agent were directly related to the peak levels of ara-G 5'-triphosphate (ara-GTP) in target cells. The aim of the present study was to develop and test strategies to increase intracellular accumulation of ara-GTP in primary human leukemia cells of myeloid and B-lymphoid origin. Three strategies were tested. First, incubations with 100 microM ara-G for 4 h produced a linear median accumulation rate of 19 microM/h (range, 2-45 microM/h; n = 15) in lymphoid leukemia cells and 16 microM/h (range, 0.5-41 microM/h; n = 11) in myeloid leukemia cells. Saturation of ara-GTP accumulation was achieved only after 6-8 h exposure in both lymphoid and myeloid leukemia cells, suggesting a rationale for prolonged infusion. Second, a dose-dependent increase in ara-GTP accumulation was observed with incubations of 10-300 microM ara-G for 3 h. Hence, dosing regimens that achieve high plasma levels of ara-G during therapy may increase cellular levels of ara-GTP. Finally, a biochemical modulation approach using in vitro incubation of leukemia cells with 10 microM 9-beta-D-arabinofuranosyl-2-fluoroadenine for 3 h, followed by either 50 or 100 microM ara-G for 4 h, resulted in a statistically significant median 1.3-fold (range, 1.1-9.0-fold; P = 0.034) and 1. 8-fold (range, 0.9-10.6 fold; P = 0.018) increase in ara-GTP compared to cells incubated with ara-G alone. Extension of these studies to ex vivo incubations confirmed our in vitro findings. These strategies will be used in the design of clinical protocols to increase ara-GTP accumulation in leukemia cells during therapy.
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PMID:Pharmacological and biochemical strategies to increase the accumulation of arabinofuranosylguanine triphosphatein primary human leukemia cells. 981 3

In a 6-month study of the morphologic reactions of spleenic immune structures to antigen attacks of varying intensity, one group of Wistar male rats was given water containing 100 opportunistic pathogens per 1 ml, the other, water containing 1,000 opportunistic pathogens per 1 ml. In the control, rats drank sterile water. In the second experimental group, spleenic sites of reproduction reduced the relative count of lymphocytes and mitoticly dividing cells and increased the counts of immature plasmocytes and macrophages. Destructively changed cells grew in number in the mantle, the marginal zone, the lymphoid nodes w/o reproduction sites, PALC and the cellular (lymphoid) aggregation in the red pulp in both experimental groups. There were immature eosinophils in the marginal zone and red pulp cellular aggregations in the second experimental group. Lymphoid nodes w/o reproduction sites and PALC showed a significant reduction in the relative count of middle lymphocytes. Relative counts of middle lymphocytes in the red pulp cellular aggregation as well as plasmocytes and macrophages were on the rise whereas the count of small lymphocytes decreased.
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PMID:[The effect of opportunistic pathogenic microflora in drinking water on the cellular composition of the splenic lymphoid tissue of rats]. 981 39

Urethane, a byproduct of fermentation found in alcoholic beverages, is carcinogenic in rodents and is classified by the International Agency for Research on Cancer as a possible human carcinogen. The United States Food and Drug Administration nominated urethane for study because of the widespread exposure of humans through the consumption of fermented foods and beverages and because of a lack of adequate dose-response data about the carcinogenicity of urethane with and without the coadministration of ethanol. Comparative studies of urethane in drinking water and in 5% ethanol were conducted to investigate possible effects of ethanol on urethane toxicity. Toxicokinetic studies of urethane in drinking water and in 5% ethanol and genetic toxicity studies of urethane in vivo and in vitro were also conducted. Groups of 10 male and 10 female F344/N rats and B6C3F1 mice, 6 weeks of age, received 0, 110, 330, 1,100, 3,300, or 10,000 ppm urethane in drinking water or in 5% ethanol for 13 weeks. Toxicokinetic evaluations were performed for urethane in the plasma of male mice after 13 weeks of administration in drinking water or 5% ethanol. The mutagenicity of urethane in Salmonella typhimurium strains TA97, TA98, TA100, TA1535, and TA1537 with and without S9 was tested at doses up to 16,666 micrograms/plate; urethane was also tested for induction of sister chromatid exchanges and chromosomal aberrations in cultured Chinese hamster ovary cells and sex-linked recessive lethal mutations and chromosomal reciprocal translocations in Drosophila melanogaster. The frequency of micronucleated erythrocytes induced in peripheral blood and bone marrow cells of mice by urethane in drinking water and in 5% ethanol was also evaluated. In rats that received urethane in drinking water, seven males and four females administered 10,000 ppm and one female administered 3,300 ppm died before the end of the study; body weight gains were reduced at these concentrations. Two males and all females given 10,000 ppm urethane in 5% ethanol died during the study, and the body weight gains of males and females that received 3,300 ppm were lower than those of the controls. Relative right kidney, liver, and lung weights of males and females and relative right testis weights of males administered 1,100 ppm or greater were generally higher than those of the controls in each study. Leukopenia and lymphopenia were observed in rats receiving urethane in either drinking water or ethanol and occurred in males receiving 330 ppm or greater and females receiving 110 ppm or greater. Other differences in hematology and clinical chemistry variables were not considered to be biologically significant. Lymphoid depletion of the spleen, lymph nodes, and thymus was observed in male and female rats receiving 1,100, 3,300, or 10,000 ppm urethane in drinking water. Cellular depletion of the bone marrow occurred in males and females in the 10,000 ppm groups. Hepatocellular fatty changes and clear cell foci of alteration were noted in the liver of males and females that received 3,300 or 10,000 ppm. The incidences of nephropathy were significantly increased in female rats that received 1,100 ppm or greater; the severity of this lesion in exposed males and females was greater than that in the controls. Females that received 330 ppm or greater had higher incidences of cardiomyopathy than the controls; the severity of this lesion was greater in males in the 10,000 ppm group and females in the 3,300 and 10,000 ppm groups than in the controls. In rats that received urethane in 5% ethanol, lymphoid depletion occurred in males and females in the 3,300 and 10,000 ppm groups. Cellular depletion of the bone marrow was observed in males and females in the 10,000 ppm groups. Only males in the 10,000 ppm group had hepatocellular fatty change (8/10) and clear cell foci (1/10); the incidence and severity of nephropathy in males and females and cardiomyopathy in males were similar to those in rats administered urethane in drinking water; however, no cardiomyopathy was observed in females receiving urethane in ethanol. The estrous cycle length of females receiving urethane in ethanol appeared to be longer than that of females receiving urethane in drinking water. Because cycle length was longer in the 10,000 ppm groups than in the controls in both the drinking water and ethanol vehicle studies, this difference may represent an exacerbation of the toxicity of urethane. A longer estrous cycle may be a sign of reproductive impairment and correlates with a decrease in female fecundity. All mice administered 10,000 ppm urethane in either vehicle died. All mice that received 3,300 ppm urethane in drinking water died, while only one male and four females receiving 3,300 ppm urethane in 5% ethanol died. Body weight gains of males and females in all 1,100 ppm groups were less than those of the respective controls, but the weight gains of mice receiving 1,100 ppm urethane in 5% ethanol were greater than those of mice receiving urethane in drinking water. The mean body weights of the lower exposure groups were similar to those of the respective controls, and there were no other differences between the body weights of mice receiving urethane in drinking water and those receiving urethane in 5% ethanol. Fluid consumption, and therefore total urethane intake, appeared lower in mice receiving the 5% ethanol vehicle than in those receiving the water vehicle. The relative right kidney, liver, and lung weights of males and females administered urethane in drinking water or ethanol were generally greater than those of the controls. Clearance of urethane from the plasma of male mice was complete within 2 hours after urethane was administered in water, but urethane was not cleared 12 hours after administration in 5% ethanol. At the end of 13 weeks of urethane administration, the plasma urethane elimination half-life was 0.8 hours; the kinetics were similar for concentrations of 110, 330, and 1,100 ppm urethane in water and in ethanol. However, at each exposure level, the plasma urethane concentration was four times greater for urethane administered in 5% ethanol than for urethane administered in drinking water, indicating a possible inhibition of urethane metabolism by ethanol. Kinetic measurements for elimination by female mice could not be obtained from the data collected. In mice administered urethane in drinking water, lung inflammation occurred in males and females that received 1,100 ppm or greater. Alveolar epithelial hyperplasia occurred in the lungs of males in the 330 and 1,100 ppm groups and females in the 1,100 ppm group; one male mouse in the 330 ppm group had an alveolar/bronchiolar adenoma (see the following summary table). Mice receiving urethane in 5% ethanol had lower incidences and severity of lung inflammation but generally greater incidences and severity of alveolar epithelial hyperplasia than mice receiving the same concentrations of urethane in drinking water. Alveolar/bronchiolar adenomas occurred in four males and one female administered urethane in ethanol. [table: see text] Nephropathy was observed in males and females that received urethane in either vehicle, and the lesions in female mice were more severe than those in male mice; ethanol did not appear to increase the incidence or severity of nephropathy. Cardiomyopathy occurred in males and females that received 1,100 or 3,300 ppm urethane in drinking water and in females that received 3,300 ppm urethane in ethanol. Lymphoid depletion occurred in mice that received 3,300 or 10,000 ppm urethane; 5% ethanol did not appear to enhance these effects. However, urethane in 5% ethanol induced ovarian atrophy; the incidence of this lesion was lower in females receiving urethane in drinking water. A concentration of 1,100 ppm urethane in either drinking water or ethanol effectively stopped estrous cycling. Urethane is clearly genotoxic in vitro and in vivo. In vitro, urethane induced mutations in Salmonella typhimurium strain TA1535 in the presence of liver S9 enzymes. Sister chromatid exchanges were induced in cultured Chinese hamster ovary (CHO) cells with and without S9. However, no induction of chromosomal aberrations was observed in CHO cells treated with urethane, with or without S9. In vivo, urethane induced sex-linked recessive lethal mutations and reciprocal translocations in germ cells of adult male Drosophila melanogaster fed urethane. Significantly increased frequencies of micronucleated erythrocytes were observed in peripheral blood obtained from male and female mice after 45 days of exposure and in bone marrow and peripheral blood obtained after 13 weeks of exposure to urethane in drinking water. There appeared to be no significant difference in the magnitude of the response in the peripheral blood micronucleus test between mice administered urethane in drinking water and mice administered urethane in 5% ethanol. In summary, concentrations of 1,100 ppm urethane or greater in drinking water caused lymphoid and bone marrow cell depletion and hepatocellular lesions and increased the severity of nephropathy and cardiomyopathy in male and female rats. The lethal effects of 10,000 ppm urethane were slightly exacerbated by 5% ethanol in female rats. Urethane administered in drinking water induced lung inflammation, alveolar and bronchiolar hyperplasia, alveolar/bronchiolar adenomas, nephropathy, cardiomyopathy, lymphoid and bone marrow cell depletion, seminiferous tubule degeneration, and ovarian atrophy and follicular degeneration in mice. In female mice, 5% ethanol appeared to exacerbate ovarian atrophy. Mice administered urethane in 5% ethanol consumed less fluid, and therefore less urethane, than mice receiving urethane in drinking water. Coadministration of urethane and ethanol inhibited the clearance of urethane from plasma. (ABSTRACT TRUNCATED)
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PMID:NTP technical report on toxicity studies of urethane in drinking water and urethane in 5% ethanol administered to F344/N rats and B6C3F1 mice. 1180 5

Worldwide pandemics of human influenza virus caused extensive morbidity and mortality around the world had been documented in the 20th century. However, the mechanisms involved in the emergence of novel influenza virus and the epidemiological factors leading to pandemics are unpredictable. Southern China is postulated as the epicentre of influenza epidemics due to its agricultural-based communities and high population density. Pandemic influenza viruses are through to arise from avian viruses through genetic reassortment among influenza viruses. An influenza virus (H5N1) known to infect only birds previously was found to infect human causing disease and death in Hong Knog in 1997 and the outbreak involved 18 patients with six deaths. Prior to the human outbreak, the H5N1 virus was found to cause extensive death in chickens in three farms in Hong Kong. The significance of this outbreak raised worldwide concern on the possibilities that such an influenza virus may become the next influenza pandemic strain. Investigations were initiated to find the source of the virus. In addition the extend of spread in individuals in contact with the index case and infected poultry was studied by H5-specific serology. Results demonstrated that individuals in close contact with the index case or with exposure to poultry were at risk of being infected. Out of the 18 cases of human infection, eleven had severe infection with symptoms of pneumonia and multi-organ failure. All severe cases presented with lower respiratory infection and lymphopenia and six eventually died. Case-fatality ratio was high among patients over 12 years of age (five out of nine). Control measures aimed at reducing exposure of human to potential H5-positive poultry were instituted which included culling of all poultry in Hong Kong, the segregation of water fowls and chicken, and the introduction of import control measures for chickens. Such measures had successfully controlled the outbreak and continuous surveillance of the poultry in Hong Kong of H5N1 infection is maintained to minimize future human exposure.
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PMID:Influenza A (H5N1) in Hong Kong: an overview. 1211 Feb 65


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