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

To clarify the mechanism of high susceptibility to infection in cirrhotics, the changes in adenylate energy charge and MTT assay in peripheral blood lymphocytes were studied in cirrhotic and noncirrhotic patients in the early postoperative period after hepatectomy. The adenylate energy charge measured by radioactive labeling of the lymphocyte adenine nucleotide pool showed no significant difference preoperatively between cirrhotics and noncirrhotics, but a significant difference was observed in the pre- and postoperative distribution of adenine nucleotide metabolites (P less than 0.01). In the cirrhotic group, the adenylate energy charge of lymphocytes decreased significantly to 0.807 +/- 0.011 on the third postoperative day compared with preoperative value (0.891 +/- 0.006, P less than 0.01) and was restored to the normal range on the fifth and tenth postoperative days (0.886 +/- 0.006, 0.899 +/- 0.014), while no significant decrease was observed in the noncirrhotic group. MTT assay revealed that lymphocyte cell function decreased significantly in cirrhotics after hepatectomy. These results indicate that, in cirrhotic patients, the energy metabolism of lymphocytes is already impaired to some extent preoperatively, and that it undergoes further deterioration when surgical stress is applied. It is suggested that the decreased energy metabolism in the lymphocyte may be responsible for the increased susceptibility to infection in postoperative cirrhotics.
 ...
PMID:Impaired energy metabolism of lymphocytes in cirrhotics after hepatectomy. 174 Sep 42

The maturing reticulocyte degrades ribosomal RNA to constituent ribonucleoside phosphates. Guanosine ribonucleotides are retained only in small amounts and pyrimidine ribonucleotides only in trace quantities. In the mature erythrocyte more than 97% of total nucleotides are the interconvertible adenosine mono-, di-, and triphosphates. High energy ATP fuels most of the reactions required to sustain viability. Unable to synthesize adenosine phosphates from small precursor molecules, the red cell relies on certain salvage pathways to replenish its losses from the adenosine phosphate pool. The most important of these involve adenosine. Adenylate kinase deficiency, when severe, is associated with nonspherocytic hemolytic anemia. A genetically-determined deficiency of pyrimidine 5'-nucleotidase prevents the normal dephosphorylation of pyrimidine ribonucleotides, and hence is characterized by the unique accumulation of pyrimidine phosphates intracellularly. Other features are chronic hemolytic anemia, splenomegaly, and a profound increase in basophilic stippling on the stained blood film. The syndrome is transmitted as an autosomal recessive disorder. A similar syndrome is found in severe lead poisoning as a consequence of nucleotidase inhibition by lead. An inherited, dominantly transmitted hemolytic anemia associated with low red cell ATP and a 45-70 fold increase in the enzymatic activity of adenosine deaminase has also been documented. The undefined molecular lesion appears to involve overproduction of an entirely normal enzyme protein. Severe deficiency of either of two sequential enzymes of purine metabolism, adenosine deaminase anemia, but by excessive accumulations of deoxyribonucleotides within red cells and lymphocytes. The clinical counterpart of each is a severe immunodeficiency state secondary to lymphopenia and lymphocyte dysfunction. Certain other rare clinical syndromes involving disturbed nucleotide metabolism also are detectable by red cell assay procedures.
 ...
PMID:Erythrocyte disorders of purine and pyrimidine metabolism. 625 19

Natural hibernation consists of torpid phases with metabolic suppression alternating with euthermic periods. Induction of torpor holds substantial promise in various medical conditions, including trauma, major surgery, and transplantation. Torpor in mice can be induced pharmacologically by 5'-AMP. Previously, we showed that during natural torpor, the reduction in body temperature results in lymphopenia via a reduction in plasma S1P. Here, we show that during torpor induced by 5'-AMP, there is a similar reduction in the number of circulating lymphocytes that is a result of their retention in secondary lymphoid organs. This lymphopenia could be mimicked by engagement of A(2B)Rs by a selective A(2B)R agonist (LUF6210) in the absence of changes in temperature and prevented by A(2B)R antagonists during 5'-AMP-induced torpor. In addition, forced cooling of mice led to peripheral blood lymphopenia, independent of A(2B)R signaling. The induction of torpor using 5'-AMP impacted the migration of lymphocytes within and between secondary lymphoid organs. During torpor, the homing into LNs was impaired, and two-photon intravital microscopy revealed that cell motility was decreased significantly and rapidly upon 5'-AMP administration. Furthermore, the S1P plasma concentration was reduced by 5'-AMP but not by LUF6210. S1P plasma levels restored upon arousal. Likely, the reduced migration in LNs combined with the reduced S1P plasma level substantially reduces lymphocyte egress after injection of 5'-AMP. In conclusion, 5'-AMP induces a state of pharmacological torpor in mice, during which, lymphopenia is governed primarily by body temperature-independent suppression of lymphocyte egress from LNs.
 ...
PMID:5'-AMP impacts lymphocyte recirculation through activation of A2B receptors. 2368 28