Erythroblast differentiation at spleen in Q137E mutant ribosomal protein S19 gene knock-in C57BL/6J mice.

We recently found that erythroblast-like cells derived from human leukaemia K562 cells express C5a receptor (C5aR) and produce its antagonistic and agonistic ligand ribosomal protein S19 (RP S19) polymer, which is cross-linked between K122 and Q137 by tissue transglutaminases. RP S19 polymer binds to the reciprocal C5aRs on erythroblast-like cells and macrophage-like cells derived from human monocytic THP-1 cells and promotes differentiation into reticulocyte-like cells through enucleation in vitro. To examine the roles of RP S19 polymer in mouse erythropoiesis, we prepared Q137E mutant RP S19 gene knock-in C57BL/6J mice. In contrast to wild-type mice, erythroblast numbers at the preliminary stage (CD71high/TER119low) in spleen based on transferrin receptor (CD71) and glycophorin A (TER119) values and erythrocyte numbers in orbital artery bloods were not largely changed in knock-in mice. Conversely, erythroblast numbers at the early stage (CD71high/TER119high) were significantly decreased in spleen by knock-in mice. The reduction of early erythroblast numbers in spleen was enhanced by the phenylhydrazine-induced pernicious anemia model knock-in mice and was rescued by a functional analogue of RP S19 dimer S-tagged C5a/RP S19. These data indicated that RP S19 polymer plays the roles in the early erythroblast differentiation of C57BL/6J mouse spleen.

[Complication of pernicious anemia during interferon-ß treatment for type C chronic hepatitis].

A 62-year-old man with chronic hepatitis C underwent interferon (IFN)-ß therapy. After treatment for a period comprising 29 months and 2 weeks, hematological results showed a decrease in white blood cell, hemoglobin, and platelet counts (WBC 2,300/µl, Hb 7.2 g/dl, PLT 4.7×10(4)/µl), and IFN therapy was stopped. Despite therapy discontinuation, the pancytopenia continued to progress with elevation of LDH (LDH 4,898 IU/l), and the patient was admitted to our hospital with suspected hematological disease. The patient underwent clinical screening, and pernicious anemia caused by vitamin B12 deficiency was diagnosed. The anemia rapidly improved with vitamin B12 treatment. Interferon is the mainstay of treatment for patients with viral hepatitis. While the adverse effects of interferon therapy are widely recognized, only a few reports have documented pernicious anemia developing during IFN-therapy. We recommend that particular attention be paid to such clinical and laboratory conditions as megaloblastic anemia when administering IFN. We also recommend checking the vitamin B12 level, as a deficiency of this vitamin may lead to the development of megaloblastic anemia.

Pernicious anemia during IFN-alpha treatment for chronic hepatitis C.

Some latent diseases, such as immune disorders, can appear during interferon-alpha (IFN-alpha) therapy. These disorders are difficult to predict because of their low prevalence in the general population. We describe a case of pernicious anemia (PA) in a patient affected by chronic hepatitis C and macrocytosis during IFN-alpha therapy. Hemoglobin (Hb) concentration reached 7.3 g/dl. Anti-intrinsic factor (IF) antibodies were present, but not antiparietal cell antibodies (APCA). Suspension of IFN-alpha and administration of vitamin B(12) resulted in normal Hb concentrations. This case is the first instance of early PA (at the second month of IFN therapy) in a patient affected by chronic hepatitis C. The only other case of PA in a patient affected by hepatitis C virus (HCV) infection occurred during the second year of maintenance IFN therapy. We recommend that particular attention be paid to such clinical and laboratory conditions as macrocytosis in administering IFN-alpha therapy for chronic hepatitis C.

Nitrous oxide anesthesia-associated myelopathy.

BACKGROUND: The role of nitrous oxide exposure in neurologic complications of subclinical cobalamin deficiency has been reported, but few cases are well documented. OBSERVATION: Two weeks after surgery for prosthetic adenoma, a 69-year-old man developed ascending paresthesia of the limbs, severe ataxia of gait, tactile sensory loss on the 4 limbs and trunk, and absent tendon reflexes. After a second surgical intervention, the patient became confused. Four months after onset, the patient had paraplegia, severe weakness of the upper limbs, cutaneous anesthesia sparing the head, and confusion. Moderate macrocytosis, low serum B12 levels, and a positive Schilling test result led to the diagnosis of pernicious anemia. Results of electrophysiologic examinations showed a diffuse demyelinating neuropathy. Magnetic resonance imaging of the spinal cord disclosed hyperintensities of the dorsal columns on T2-weighted images. CONCLUSIONS: Pernicious anemia can result in severe neurologic symptoms with only mild hematologic changes. The role of nitrous oxide anesthesia in revealing subclinical B12 deficiency must be emphazised. Magnetic resonance imaging of the spinal cord might be helpful in making the diagnosis.

Myelotoxic, neurotoxic and reproductive adverse effects of nitrous oxide.

N2O is a relatively safe general anaesthetic under normal medical and dental anaesthetic use. It is more likely to produce megaloblastosis or neuropathy when used repetitively or for periods longer than 3 hours or in individuals with vitamin B12 deficiencies. The mechanism responsible for its myelotoxicity, neurotoxicity and most likely its reproductive toxicity, involves its inhibition of MetSyn and the resulting reduction in SAM and THF levels. Administration of folinic acid or methionine have been shown to protect against megaloblastosis and neurotoxicity occurring following N2O administration. Occupational N2O exposure of medical and dental personnel during its use as an analgesic is not likely to produce adverse reproductive outcomes except in B12-deficient individuals or in those routinely exposed to high N2O levels.

Toxicological and clinical aspects of cyanide metabolism.

This contribution deals with the occurrence of cyanide and its biological pathways in the body. Especially possibilities of detoxification are pointed out. Intoxications are caused by acute and chronical cyanide uptake. Tobacco amblyopia, retrobulbar neuritis in pernicious anaemia, Leber's optic atrophy, Nigerian nutritional neuropathy, and sterility in female heavy smokers are attributed to cyanide intoxication. Various methods for treating acute and chronic cyanide intoxication are discussed.