scholarly journals Congenital Nonspherocytic Hemolytic Anemia, Associated with Glutathione Deficiency of the Erythrocytes

Blood ◽  
1966 ◽  
Vol 27 (2) ◽  
pp. 145-166 ◽  
Author(s):  
H. K. PRINS ◽  
M. OORT ◽  
J. A. LOOS ◽  
C. ZÜRCHER ◽  
T. BECKERS
Keyword(s):  
Hemolytic Anemia ◽  
Autosomal Recessive ◽  
Reduced Glutathione ◽  
Normal Range ◽  
Serological Method ◽  
No Formation ◽  
Glycolytic Activity ◽  
Glutathione Deficiency ◽  
Autosomal Recessive Pattern

Abstract 1. A new biochemical defect of erythrocytes is described: glutathione deficiency (reduced glutathione less than 10 per cent of the amount of reduced glutathione in normal erythrocytes). 2. The defect is associated with a clinical picture of congenital nonspherocytic hemolytic anemia which is fairly well compensated. 3. The results of a family study are consistent with an autosomal recessive pattern of inheritance. 4. Labeling with Na2Cr51O4 has a damaging effect on glutathione-deficient erythrocytes. The erythrocyte life span, as estimated by a serological method (Ashby), was markedly shortened (30 days instead of 100-120 days). 5. Red cell destruction could be increased by the administration of primaquine. 6. Secondary to the glutathione deficiency, low glyoxalase activity was observed. The glutathione-reducing capacity, glycolytic activity, and the ATP level of the abnormal red cells were found to be within the normal range. 7. On incubation of the glutathione-deficient erythrocytes in vitro with glycine-C14 and glutamine-C14, no formation of labeled glutathione could be demonstrated.

scholarly journals Sulfhemoglobinemia and Acute Hemolytic Anemia with Heinz Bodies Following Contact with a Fungicide— Zinc Ethylene Bisdithiocarbamate—in a Subject with Glucose-6-Phosphate Dehydrogenase Deficiency and Hypocatalasemia

Blood ◽  
1963 ◽  
Vol 21 (4) ◽  
pp. 484-494 ◽  
Author(s):  
JACK PINKHAS ◽  
MEIR DJALDETTI ◽  
HENRY JOSHUA ◽  
CHAIM RESNICK ◽  
ANDRÉ DE VRIES
Keyword(s):  
Red Blood Cells ◽  
Hemolytic Anemia ◽  
Blood Cells ◽  
Dehydrogenase Deficiency ◽  
Reduced Glutathione ◽  
Body Formation ◽  
Low Glucose ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Enzymatic Defect

Abstract Sulfhemoglobinemia associated with Heinz body formation and acute hemolytic anemia following contact with a fungicide, zinc ethylene bisdithiocarbamate, is described in a Persian Jew whose red blood cells had low glucose-6-phosphate dehydrogenase activity with low and unstable reduced glutathione and low catalase activity. The fungicide, similarly to acetylphenylhydrazine, was capable of decreasing in vitro the reduced glutathione of the patient’s red blood cells, as well as of those of other subjects with the same enzymatic defect. The sulfhemoglobinemia and the hemolytic anemia are considered to have been produced independently by the fungicide, the glucose-6-phosphate dehydrogenase deficiency having played a role only in the latter. The possibility that the hypocatalasemia was a factor in rendering the patient’s red blood cells sensitive to the hemolysis- and sulfhemoglobin-producing action of the fungicide is discussed. The importance of zinc ethylene bisdithiocarbamate as a sulfhemoglobin-producing and hemolytic agent is stressed, in view of the widespread use of this fungicide.

A NEW CONGENITAL HEMOLYTIC ANEMIA WITH DEFORMED ERYTHROCYTES (? "STOMATOCYTES") AND REMARKABLE SUSCEPTIBILITY OF ERYTHROCYTES TO COLD HEMOLYSIS IN VITRO

PEDIATRICS ◽  
1965 ◽  
Vol 35 (6) ◽  
pp. 906-915
Author(s):  
Gerald Miller ◽  
Philip L. Townes ◽  
James B. MacWhinney
Keyword(s):  
Hemolytic Anemia ◽  
Hereditary Spherocytosis ◽  
Reduced Glutathione ◽  
Laboratory Data ◽  
Osmotic Fragility ◽  
Clinical Findings ◽  
Congenital Ptosis ◽  
New Variant ◽  
Congenital Hemolytic Anemia

A new variant of congenital hemolytic anemia is described. The principal clinical findings are moderately severe hemolytic anemia, jaundice, and splenomegaly; congenital ptosis of an eyelid may possibly be an associated anomaly. Splenectomy resulted in clinical improvement but did not completely arrest abnormal hemolysis nor alter red cell abnormalities. Laboratory data are presented which characterize the condition; the principal abnormalities detected thus far are: (1) abnormal morphology of the erythrocytes ("stomatocytes"); ) increased osmotic fragility and autohemolysis; (3) storage instability greater at 5°C than at 37°C; (4) decreased concentration of reduced glutathione despite normal G-6-P-D and G-6-P-D coupled glutathione reductase activities. The disorder is compared with hereditary spherocytosis and hereditary stomatocytosis; similarities to and differences from these disorders are reviewed.

A DEFECT OF GLUTATHIONE METABOLISM IN ERYTHROCYTES FROM PATIENTS WITH A NAPHTHALENE-INDUCED HEMOLYTIC ANEMIA

PEDIATRICS ◽  
1958 ◽  
Vol 22 (3) ◽  
pp. 461-471
Author(s):  
W. H. Zinkham ◽  
B. Childs
Keyword(s):  
Hemolytic Anemia ◽  
Newborn Infant ◽  
Whole Blood ◽  
Reduced Glutathione ◽  
Stability Test ◽  
Glutathione Metabolism ◽  
In Vitro Tests ◽  
Stability Tests

Four patients are reported who suffered hemobytic anemia after exposure to naphthalene. These were all Negroes; three were male and one female. All the patients were shown by determinations of concentrations of glutathione in whole blood and the glutathione stability test to possess erythrocytes with a defect of glutathione metabolism. One of these patients was a newborn infant to whom naphthalene and its metabolites must have been delivered through the placenta, since both he and his mother had profound hemolytic anemia, but she alone ingested moth balls. In-vitro tests are reported showing the effects of naphthalene and its metabolites on the reduced glutathione of the erythrocytes of the patients. Naphthalene itself is innocous while alpha-naphthoquinone and alpha-naphthol lowered the concentration of reduced glutathione of the erythrocytes in lower dilutions than did beta-naphthoquinone and beta-naphthol. Repeated stability tests done with the erythrocytes of the infant and covering a period of more than 3 months gave support to the hypothesis that the defect in glutathione metabolism expresses itself only in older erythrocytes.

Influence of Certain Drugs on the Adhesiveness of Human, Rat, and Rabbit Blood Platelets in Vitro

1965 ◽  
Vol 13 (02) ◽  
pp. 428-438 ◽  
Author(s):  
K Reber ◽  
A Studer
Keyword(s):  
Sodium Citrate ◽  
Blood Platelets ◽  
Drug Application ◽  
Normal Range ◽  
Blood Samples ◽  
Serotonin Antagonist ◽  
Thrombocyte Count ◽  
Particle Count ◽  
Rabbit Blood

SummaryThis is a comparative study of the methods described by H. P. Wright and O’Brien for determining the adhesiveness of thrombocytes. An attempt is made to characterize and statistically correlate both techniques. With the aid of a Coulter Counter for thrombocyte counts, a normal range is presented for human, rat, and rabbit blood. Anticoagulants used are sodium citrate and Heparin.The influence of Cocaine and the Serotonin antagonist Ro 3-0837 was studied on these same substrates, to determine a pharmacological interference with results of either Wright’s test or O’Brien’s. Both drugs are found to induce a statistically significant increase in the “thrombocyte count” as compared to the corresponding controls. These effects are not real but to be attributed to an increase in particle count due to thrombocyte fragmentation as a consequence of drug application. There is no evidence for the claim that these drugs decrease the adhesiveness of thrombocytes.Numerical results of both tests often show a high and statistically significant correlation, especially following the addition of Ro 3-0837. Such is not true of individual blood samples to which no drug has been added. Evidentally, both tests are not specific for the same characteristic of normal blood platelets. But, when Ro 3-0837 is added, the breakdown of unstable platelets is induced; and the corresponding increase in count of thrombocyte fragments is expressed by both tests in the same fashion.

Renal Cortical Slices: An In Vitro Model for Kidney Metabolism and Toxicity

1992 ◽  
Vol 20 (1) ◽  
pp. 71-76
Author(s):  
Andrea Trevisan ◽  
Stefano Maso ◽  
Paola Meneghetti
Keyword(s):  
Wistar Rats ◽  
Reduced Glutathione ◽  
Organic Anion ◽  
Cortical Slice ◽  
Lactate Dehydrogenase Release ◽  
Age Related ◽  
Renal Cortical Slice ◽  
Male Wistar Rats ◽  
Vitro Model

The in vitro renal cortical slice model was used to study: 1) the effects on the kidney of some haloalkanes and haloalkenes using 3-month-old male Wistar rats; 2) influence of age and sex on renal cortical slice indices in non-treated rats; and 3) effects of 1,2-dichloropropane on the slices after pretreatment of 3-month-old male Wistar rats with DL-butathionine-[S,R]-sulphoximine. The most nephrotoxic chemical used was 1,3-dichloropropene, which caused a total depletion in the levels of reduced glutathione, a high peroxidation of lipid (about three thousand-fold with respect to control), a significant release of tubular enzymes into the medium, and loss of organic anion ( p-aminohippurate) accumulation. All the chemicals affected the cytosol more than the brush border. The most remarkable age-related differences in the untreated slices were the progressive decrease of reduced glutathione (p<0.05 from three months of age), and an increase in lactate dehydrogenase release into the medium (p<0.05 from six months of age). By contrast, sex differences were slight. The ‘treatment with 1,2-dichloropropane of slices prepared from rats pretreated with DL-butathionine-[S,R]-sulphoximine significantly increased the depletion of glutathione content (p<0.05) and malondialdehyde release in the medium (p<0.001) caused by the solvent alone.

scholarly journals DJ-1 regulates the integrity and function of ER-mitochondria association through interaction with IP3R3-Grp75-VDAC1

2019 ◽  
Vol 116 (50) ◽  
pp. 25322-25328 ◽  
Author(s):  
Yi Liu ◽  
Xiaopin Ma ◽  
Hisashi Fujioka ◽  
Jun Liu ◽  
Shengdi Chen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Cellular Mechanism ◽  
Loss Of Function ◽  
Wild Type ◽  
Calcium Efflux ◽  
And Function ◽  
The Brain ◽  
Early Onset Parkinson’S Disease

Loss-of-function mutations in DJ-1 are associated with autosomal recessive early onset Parkinson’s disease (PD), yet the underlying pathogenic mechanism remains elusive. Here we demonstrate that DJ-1 localized to the mitochondria-associated membrane (MAM) both in vitro and in vivo. In fact, DJ-1 physically interacts with and is an essential component of the IP3R3-Grp75-VDAC1 complexes at MAM. Loss of DJ-1 disrupted the IP3R3-Grp75-VDAC1 complex and led to reduced endoplasmic reticulum (ER)-mitochondria association and disturbed function of MAM and mitochondria in vitro. These deficits could be rescued by wild-type DJ-1 but not by the familial PD-associated L166P mutant which had demonstrated reduced interaction with IP3R3-Grp75. Furthermore, DJ-1 ablation disturbed calcium efflux-induced IP3R3 degradation after carbachol treatment and caused IP3R3 accumulation at the MAM in vitro. Importantly, similar deficits in IP3R3-Grp75-VDAC1 complexes and MAM were found in the brain of DJ-1 knockout mice in vivo. The DJ-1 level was reduced in the substantia nigra of sporadic PD patients, which was associated with reduced IP3R3-DJ-1 interaction and ER-mitochondria association. Together, these findings offer insights into the cellular mechanism in the involvement of DJ-1 in the regulation of the integrity and calcium cross-talk between ER and mitochondria and suggests that impaired ER-mitochondria association could contribute to the pathogenesis of PD.

FcγRIII (CD16)-Deficient Mice Show IgG Isotype-Dependent Protection to Experimental Autoimmune Hemolytic Anemia

Blood ◽  
1998 ◽  
Vol 92 (11) ◽  
pp. 3997-4002 ◽  
Author(s):  
Dirk Meyer ◽  
Carsten Schiller ◽  
Jürgen Westermann ◽  
Shozo Izui ◽  
Wouter L. W. Hazenbos ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Knock Out ◽  
Effector Cells ◽  
Igg Isotypes ◽  
Knock Out Mice ◽  
Deficient Mice ◽  
Experimental Autoimmune

Abstract In autoimmune hemolytic anemia (AIHA), there is accumulating evidence for an involvement of FcγR expressed by phagocytic effector cells, but demonstration of a causal relationship between individual FcγRs and IgG isotypes for disease development is lacking. Although the relevance of IgG isotypes to human AIHA is limited, we could show a clear IgG isotype dependency in murine AIHA using pathogenic IgG1 (105-2H) and IgG2a (34-3C) autoreactive anti–red blood cell antibodies in mice defective for FcγRIII, and comparing the clinical outcome to those in wild-type mice. FcγRIII-deficient mice were completely resistent to the pathogenic effects of 105-2H monoclonal antibody, as shown by a lack of IgG1-mediated erythrophagocytosis in vitro and in vivo. In addition, the IgG2a response by 34-3C induced a less severe but persistent AIHA in FcγRIII knock-out mice, as documented by a decrease in hematocrit. Blocking studies indicated that the residual anemic phenotype induced by 34-3C in the absence of FcγRIII reflects an activation of FcγRI that is normally coexpressed with FcγRIII on macrophages. Together these results show that the pathogenesis of AIHA through IgG1-dependent erythrophagocytosis is exclusively mediated by FcγRIII and further suggest that FcγRI, in addition to FcγRIII, contributes to this autoimmune disease when other IgG isotypes such as IgG2a are involved.

Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 692-694 ◽  
Author(s):  
Daniel F. Wallace ◽  
Palle Pedersen ◽  
Jeannette L. Dixon ◽  
Peter Stephenson ◽  
Jeffrey W. Searle ◽  
...  
Keyword(s):  
Iron Transport ◽  
Autosomal Recessive ◽  
Iron Homeostasis ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Hfe Gene ◽  
Excess Iron ◽  
Chromosome 1Q ◽  
Australian Family ◽  
Autosomal Recessive Pattern

Abstract Hemochromatosis is a common disorder characterized by excess iron absorption and accumulation of iron in tissues. Usually hemochromatosis is inherited in an autosomal recessive pattern and is caused by mutations in the HFE gene. Less common non-HFE–related forms of hemochromatosis have been reported and are caused by mutations in the transferrin receptor 2 gene and in a gene localized to chromosome 1q. Autosomal dominant forms of hemochromatosis have also been described. Recently, 2 mutations in theferroportin1 gene, which encodes the iron transport protein ferroportin1, have been implicated in families with autosomal dominant hemochromatosis from the Netherlands and Italy. We report the finding of a novel mutation (V162del) in ferroportin1 in an Australian family with autosomal dominant hemochromatosis. We propose that this mutation disrupts the function of the ferroportin1 protein, leading to impaired iron homeostasis and iron overload.

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