Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The modifications of the electrofocusing pattern, the immunological reactivity and the kinetic properties of glucose 6 phosphate dehydrogenase have been studied in malignant blood cells of various leukemias and myeloproliferative disorders. 1. Granulocytic G-6PD forms with decreased isoelectric points have been found in all the acute myeloid leukemias and erythroleukemias, and in most of the chronic granulocytic leukemias and myelofibrosis. In contrast, granulocytic G-6PD from patients with polycythemia vera always was normal. On the same way leukemic lymphocyte or lymphoblast G-6PD was identical to that from normal lymphocytes. 2. The ratio of enzymatic activity to immunological reactivity (=molecular specific activity) was markedly decreased in the myeloblasts of two patients with acute myeloid leukemia, and in the erythroblast-rich cellular fraction of a patient with erythroleukemia. In these cells the decrease of molecular specific activity was parallel to the alteration of the electrofocusing pattern of G-6PD. 3. The enzymatic forms with decreased isoelectric point also exhibited an altered affinity for glucose 6 phosphate. These modifications are post translational alterations of the neosynthesized G-6PD, since this enzyme is a single molecule, coded by the same gene in all tissues; they seem to correspond to an accelerated molecular aging due to an increased concentration of "G-6PD modifying factors". The significance of such an increased concentration of these G-6PD modifying factors in malignant cells is discussed.
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PMID:Post translational modifications of glucose-6-phosphate dehydrogenase in human leukemias. 122 85

The biologic basis for the elevated histochemical reduction of nitroblue tetrazolium dye (NBT) in neutrophils from patients with acute bacterial infection or polycythemia vera was studied. A precipitin reaction followed mixing NBT with heparin. NBT was reduced after phagocytosis of this complex (H-NBT) by polymorphonuclear leukocytes (PMNs). Ingestion required divalent cations and was facilitated by the presence of complement. H-NBT incubated with normal but not with C2-deficient human serum converted native C3 to its inactive form. Phagocytic indices were determined in patients and controls by measuring O(2) utilization and hexose monophosphate shunt activity and by visually counting cell-associated latex particles. Significant elevations above controls were observed in phagocytes isolated from all patients with elevated histochemical NBT scores when H-NBT complex, latex, or zymosan was employed as the phagocytic particle. Increased indices were observed in the presence of fresh AB serum, heat-inactivated AB serum, or without serum. Serum from patients with elevated NBT scores did not alter phagocytosis in control phagocytes. With NADH and NADPH as substrates, total NBT diaphorase activity of sonicated leukocytes was normal in all patients. These results suggest that increased phagocytic capacity of PMNs is the primary cause of increased histochemical NBT reduction. The PMNs of patients with acute bacterial infection or polycythemia vera may have alterations in their cell membranes which lead to an enhanced rate of phagocytosis.
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PMID:Enhanced phagocytic capacity. The biologic basis for the elevated histochemical nitroblue tetrazolium reaction. 415 97

An intensive care program was offered to all insulin-dependent, pregnant diabetic women who presented to The New York Hospital Obstetrical Clinic in their eighth week or less of gestation. The patients were hospitalized for 1 wk to normalize their blood glucose and to teach the technique of self-monitored glucose determination, diet and exchange lists, and the method to titrate insulin according to the blood glucose determination. The mean blood glucose for the first 10 patients accepted to the program was 169 mg/dl at the start of the program with a mean hemoglobin A1c of 9.4% for the group (normal < 5.5%) and glucosuria up to 50 g/24 h. After discharge, mean glucose was 91 mg/dl, and urinary glucose excretion was 1.4 g/24 h. HbA1c fell into the normal range 5 wk after normoglycemia was achieved (3.4%) (nl < 5.5%). Normoglycemia was maintained as outpatients until 3 wk before delivery when the patients were readmitted for tests of fetal well-being. Mean weight gain for the mothers was 12.2 kg. Mean glucose at delivery was 87 mg/dl and HbA1c was 3%. Hormonal profiles (hCG, hPRL, estrogens, progesterone, hPL) normalized after normoglycemia was achieved and remained normal until delivery. Mean gestational age at time of delivery was 38.8 wk with a mean infant birth weight of 2988 g. No infant manifested hypoglycemia, hypocalcemia, erythremia, or respiratory disease. The use of self-monitored blood glucose allows for optimal care of the insulin-dependent, pregnant diabetic woman while she remains at home with her family.
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PMID:Management of the pregnant, insulin-dependent diabetic woman. 699 70

A patient with polycythemia rubra vera had had a leukocyte count between 55,000 and 86,000/cu mm and had had serum glucose levels as low as 8 mg/dL. Despite these low serum glucose values, the patient was asymptomatic, and a more careful investigation disclosed that the hypoglycemia was artifactual. This phenomenon, reported in other leukemic states, to our knowledge, has not been previously described in patients with polycythemia rubra vera. Our case broadens the spectrum of the causes of artifactual low serum glucose concentration due to excessive glucose consumption by the WBCs. This phenomenon is related to extreme leukocytosis, regardless of the underlying disease. Unnecessary workup for hypoglycemia can be avoided if its artifactual nature is suspected in any patient with a reported low serum glucose level and high WBC count.
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PMID:Polycythemia rubra vera and artifactual hypoglycemia. 713 67

This study was designed to test the feasibility of a patient-monitored glucose determination program to establish and maintain normal blood glucose levels. Ten pregnant women, who were insulin-dependent diabetics prior to becoming pregnant and who were in their eighth week or less of pregnancy, were offered the program. All 10 accepted and continued the program for the duration of their pregnancy. Normal plasma glucose (60 to 140; mean = 80 mg/dl) levels were achieved after one week of the program and were maintained throughout the pregnancy as documented by 5 to 8 blood glucose determinations a day. The hemoglobin A1c level, which was elevated in all 10 patients at the start (9.4 +/- 1.6 per cent) of the program, fell into the normal range (2 to 5.0 per cent) five weeks after glucose values became normal. Serum estradiol (0.8 +/- 0.6 ng/ml), serum prolactin (10 +/- 9 ng/ml) and serum human chorionic gonadotropin (5,500 +/- 1,700 ng/ml), although all abnormal at the start of the program, became normal after glucose control was achieved (program weeks 4, 5 and 6, respectively). The infants showed no signs of macrosomnia (2,988 +/- 959 g), hypoglycemia, hyperbilirubinemia, hypocalcemia, erythremia or respiratory distress. Therefore, a program to maintain normal blood glucose levels during a diabetic patient's pregnancy is not only possible but may also improve the pregnancy and the outcome.
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PMID:Feasibility of maintaining normal glucose profiles in insulin-dependent pregnant diabetic women. 735 Jul 96

A case of posttransplant erythrocytosis in a 51-year-old diabetic man is described. This problem, which can occur in 5 to 15% of renal transplant patients, can result from a contracted plasma volume (diuretics, pressure natriuresis, or glycosuria) or from a true elevation in red blood cell mass. Once the diagnosis of true erythrocytosis is made by a radiolabeled red blood cell mass study, secondary causes such as hypoxia, liver disease, polycythemia rubra vera, renal artery stenosis, and cystic kidney disease should be excluded. Posttransplant erythrocytosis has only been observed in renal transplant recipients and appears to be more frequent with cyclosporine compared with azathioprine therapy. An inappropriately high level of erythropoietin has been described in some, but not all patients, suggesting stimulation of erythropoietin production as the mechanism. Posttransplant erythrocytosis can be associated with an increased incidence of thrombotic events. The presence of this potential complication has prompted intervention to maintain the hematocrit below 50 to 55%. Measures such as discontinuation of diuretics as well as better control of blood pressure and plasma glucose should be used to facilitate the correction of extracellular volume contraction. Phlebotomy has been the most accepted intervention to intermittently lower the hematocrit when needed, but this can lead to iron deficiency. Newer therapeutic modalities are now being used to treat the problem medically. Theophylline, which reduces adenosine-mediated erythropoietin synthesis, is effective but may be associated with side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Posttransplant erythrocytosis: case report and review of newer treatment modalities. 831 81

The hypothalamic suprachiasmatic nucleus (SCN), a master circadian oscillator in mammals, contains VIP-neurons. In our study on the mechanism of the central regulation of glucose metabolism in rats, we obtained following results: 1) intracranial injection of either 2-deoxy-D-glucose (2DG) or VIP elicited hyperglycemia by enhancing neural activities of the sympathetic nerves and by the suppression of the insulin secretion and enhances of secretions of adrenaline and glucagon; 2) bilateral lesions of the SCN eliminated the hyperglycemia and sympathetic excitation induced by intracranial injection of 2DG, and intracranial administration of VIP restored the 2DG-hyperglycemia; 3) infusion of VIP-antisense oligo in the SCN reduced the VIP content in the SCN and abolished the 2DG-hyperglycemia, and intracranial injection of VIP restored the 2DG-hyperglycemia in rats infused the VIP-antisense oligo; 4) intrapancreatic injection of pseudorabies virus (PRV, Bartha), which is retrogradedly transported, caused the transfer of PRV to VIP-neurons in the SCN, and denervations of both the sympathetic and parasympathetic nerves innervating the pancreas eliminated the retrograde transport of PRV to VIP-neurons in the SCN. These findings suggest that VIP-neurons in the SCN regulate the blood glucose level through the enhancement of the sympathetic activity.
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PMID:[Role of VIP-neurons in the hypothalamic suprachiasmatic nucleus in the control of blood glucose]. 1505 40

Myelofibrosis with myeloid metaplasia (MMM) is the end stage of the Philadelphia-negative chronic myeloproliferative disorders, the classical clinical phenotype being featured by leukoerythroblastic anemia, bone marrow fibrosis and enlargement of the spleen and liver. In the early prefibrotic phase a proportion of the patients may be wrongly classified as having essential thrombocythemia (ET). Some patients with ET may also develop polycythemia vera (PV) and without a history of phlebotomies patients with primary myelofibrosis (PMF) are indistinguishable from those patients developing myelofibrosis during the course of polycythemia vera. Studies of the JAK2-mutational burden have yielded solid support to the concept of a biological continuum from JAK2-positive "ET" to JAK2-positive PMF. The statement is presented that MMM is the advanced stage of an untreated disseminated hematological cancer which accordingly should be treated upfront when the disease presents in the very early stage as ET and PV, and when the cancer stem cells - the clonal CD34+ cells - have still not egressed from the bone marrow ("carcinoma in situ"). Based upon most recent studies showing that alpha-interferon is able to induce complete and sustained molecular remissions in patients with PV it is argued that we have to change our therapeutic attitude from a "wait and watch strategy" to early upfront treatment of ET and PV. In the "metabolic syndrome" normalisation of elevated blood glucose levels has been a very important therapeutic strategy to decrease the risk of thrombotic complications consequent to in vivo platelet-, granulocyte and endothelial cell activation, which are also considered of utmost importance for the development of thrombosis in ET and PV patients. Normalisation of elevated blood cell counts in the early phase of the "chronic myeloproliferative syndromes" - ET and PV - should be the therapeutic target in the future using alpha-interferon as monotherapy or in combination with conventional (hydroxyurea and anagrelide) and novel agents (JAK2-inhibitors). By this strategy preliminary reports in PV patients of minimal residual disease with normalisation of the bone marrow during long-term alpha-interferon treatment may be further substantiated in larger series of patients, hopefully being followed by a reduction in the risk of thrombohemorrhagic complications and ultimately the development of severe bone marrow fibrosis and myeloid metaplasia.
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PMID:Myelofibrosis with myeloid metaplasia: the advanced phase of an untreated disseminated hematological cancer. Time to change our therapeutic attitude with early upfront treatment? 1863 52

The central nervous system plays an important role in the regulation of energy balance and glucose homeostasis mainly via controlling the autonomic output to the visceral organs. The autonomic output is regulated by hormones and nutrients to maintain adequate energy and glucose homeostasis. Insulin action is mediated via insulin receptors (IR) resulting in phosphorylation of insulin receptor substrates (IRS) inducing activation of downstream pathways. Furthermore, insulin enhances transient receptor potential vanilloid type 1 (TRPV1) mediated currents. Activation of the TRPV1 receptor increases excitatory neurotransmitter release in autonomic centers of the brain, thereby impacting energy and glucose homeostasis. The aim of this study is to determine co-expression of IRS2 and TRPV1 receptors in the paraventricular nucleus of the hypothalamus (PVN) and dorsal motor nucleus of the vagus (DMV) in the mouse brain as well as expression of IRS2 and TRPV1 receptors at liver-related preautonomic neurons pre-labeled with a trans-neural, viral tracer (PRV-152). The data indicate that IRS2 and TRPV1 receptors are present and co-express in the PVN and the DMV. A large portion (over 50%) of the liver-related preautonomic DMV and PVN neurons expresses IRS2. Moreover, the majority of liver-related DMV and PVN neurons also express TRPV1 receptors, suggesting that insulin and TRPV1 actions may affect liver-related preautonomic neurons.
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PMID:Immunohistochemical localization of transient receptor potential vanilloid type 1 and insulin receptor substrate 2 and their co-localization with liver-related neurons in the hypothalamus and brainstem. 2162 Mar 79

The autonomic regulation of hepatic metabolism offers a novel target for the treatment of non-alcoholic fatty liver disease (NAFLD). However, the molecular characteristics of neurons that regulate the brain-liver axis remain unclear. Since mice lacking neuronal lipoprotein lipase (LPL) develop perturbations in neuronal lipid-sensing and systemic energy balance, we reasoned that LPL might be a component of pre-autonomic neurons involved in the regulation of hepatic metabolism. Here, we show that, despite obesity, mice with reduced neuronal LPL (NEXCreLPLflox (LPL KD)) show improved glucose tolerance and reduced hepatic lipid accumulation with aging compared to wilt type (WT) controls (LPLflox). To determine the effect of LPL deficiency on neuronal physiology, liver-related neurons were identified in the paraventricular nucleus (PVN) of the hypothalamus using the transsynaptic retrograde tracer PRV-152. Patch-clamp studies revealed reduced inhibitory post-synaptic currents in liver-related neurons of LPL KD mice. Fluorescence lifetime imaging microscopy (FLIM) was used to visualize metabolic changes in LPL-depleted neurons. Quantification of free vs. bound nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) revealed increased glucose utilization and TCA cycle flux in LPL-depleted neurons compared to controls. Global metabolomics from hypothalamic cell lines either deficient in or over-expressing LPL recapitulated these findings. Our data suggest that LPL is a novel feature of liver-related preautonomic neurons in the PVN. Moreover, LPL loss is sufficient to cause changes in neuronal substrate utilization and function, which may precede changes in hepatic metabolism.
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PMID:Neuronal Lipoprotein Lipase Deficiency Alters Neuronal Function and Hepatic Metabolism. 3299 80


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