Expression of embryonic zeta-globin and epsilon-globin chains in a 10- year-old girl with congenital anemia

A 10-year-old Danish girl with congenital anemia is described. At birth, she had severe anemia and erythroblastosis and was transfused a number of times during the first year. The need for transfusions has since declined steadily. Her reticulocyte counts varied between 2% and 15%, and her bone marrow aspirate showed some dyserythropoietic features. Her hemoglobin F level was consistently elevated, up to as much as 41%. Her erythrocytes had a normal level of I antigen but an undetectable level of i antigen. Moreover, embryonic zeta-globin and epsilon-globin chains were present in some of her circulating erythrocytes. These findings may represent the manifestations of a new variant of congenital anemia.     

Preventive and curative effect of methanolic extract of Gardenia gummifera Linn. f. on thioacetamide induced oxidative stress in rats

ObjectiveTo evaluate the antioxidant and antihepatotoxic effect of methanolic extract of Gardenia gummifera Linn. f. root (MEGG) on thioacetamide (TAA) induced oxidative stress in male Wistar rats.MethodsIn the preventive study, rats were administered with 125 and 250 mg/kg of MEGG for 9 days prior to TAA administration (100 mg/kg s.c.). In post-treatment groups, rats were treated with MEGG at doses of 125 and 250 mg/kg, 2, 24 and 48 h after TAA intoxication. Silymarin was used as a standard drug control (100 mg/kg). Hepatotoxicity was assessed by quantifying the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The antioxidant potential of MEGG was evaluated by the estimation of catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation [thiobarbituric acid reactive substances (TBARS)] in hepatic and renal tissues. Histopathological changes were also evaluated.ResultsMEGG significantly (P≤0.05) prevented the elevation of serum AST, ALT, ALP, LDH and tissue malondialdehyde levels in both experimental groups, when compared to the TAA alone treated groups. The rats receiving TAA plus MEGG exhibited significant (P≤0.05) increases in hepatic and renal antioxidant activities including GSH, GST, GR, GPx and CAT levels. Quantification of histopathological changes also supported the dose dependent protective effects of MEGG.ConclusionsThese observations suggest that MEGG has dose dependent hepatoprotective and antioxidant effect against TAA induced oxidative stress.     

Upregulation of proinflammatory cytokine production in response to bacterial pathogen-associated molecular patterns in dogs with diabetes mellitus undergoing insulin therapy

Background

Metabolic alterations associated with diabetes mellitus alter innate immunity. Dogs often develop infectious or inflammatory complications related to diabetes mellitus, yet little is known about the effects of diabetes mellitus on the immune system in this species.

Methods

Prospective evaluation in dogs with poorly regulated spontaneous type 1 diabetes mellitus (T1DM). In vitro leukocyte cytokine response to lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PG) was compared between dogs with T1DM and healthy dogs. Additionally, the effect of acute in vitro glucose exposure on leukocyte tumor necrosis factor (TNF) production from healthy dogs was measured.

Results

Leukocytes from dogs with T1DM had significantly greater TNF production after LTA and PG stimulation compared with leukocytes from healthy dogs. Leukocyte interleukin (IL)-6 production was greater after stimulation with LPS, LTA, PG, and phosphate-buffered saline in the T1DM group. No such difference was noted when evaluating IL-10 production between groups regardless of stimulant. Dogs with T1DM had significantly greater IL-6 to IL-10 production ratios than healthy dogs. Acute exposure to dextrose did not augment cytokine production from healthy canine leukocytes.

Conclusions

Dogs with T1DM have altered innate immunity characterized by upregulation of proinflammatory cytokine production without a concurrent change in anti-inflammatory cytokine production. This may be one explanation for the common infectious and inflammatory complications associated with T1DM in dogs.     

Leukemic-like membrane properties acquired by B lymphocytes when depleted of 185,000-dalton macromolecular insoluble cold globulin

Human peripheral blood lymphocytes can be phenotypically identified by the presence of one or both of two proteins, 225,000-dalton macromolecular insoluble cold globulin (225-MICG) and 185,000-dalton MICG (185-MICG). T cells synthesize and insert into their plasma membrane 225-MICG, null cells 185-MICG, and B cells both 225 and 185- MICG. In contrast, the monoclonal B cells of chronic lymphocytic leukemia are characterized by the presence of 225-MICG and the absence of 185-MICG. We have recently found it possible to chemically deplete 185-MICG from viable normal B cells by treating them with diisopropylfluorophosphate (DFP), thus making normal B cells phenotypically resemble leukemic cells. In the present report we determined whether certain peculiar properties of these leukemic cells would be associated with the normal B cells chemically depleted of 185- MICG. In normal B cells, SIg diffuses in the lipid bilayer to form clusters and caps under appropriate conditions, while in chronic lymphocytic leukemia (CLL) cells this does not occur. Normal B cells depleted of 185-MICG fail to undergo capping of SIg or surface MICG under appropriate conditions. Both DFP-treated B cells and CLL cells tend to rupture when smeared on a glass slide. Both CLL cells and DFP- treated B cells fail to secrete 225-MICG after it has been synthesized intracellularly. The relationship of these findings to the mechanisms of secretion and capping are discussed.