Agranulocytosis induced by antithyroid therapy: effects of treatment with granulocyte colony stimulating factor.

A 26-year-old woman was admitted to hospital with high fever, severe tonsillitis, and gastroenteritis. Because of Graves' disease she had been treated with methimazole for 18 months. Leukopenia and agranulocytosis in combination with a typical bone marrow, exhibiting a complete arrest of myelopoiesis at the stage of promyelocytes led to the diagnosis of an antithyroid therapy induced agranulocytosis. After 1 week of antibiotic treatment without changes in neutrophil counts, granulocyte colony stimulating factor treatment at a dose of 300 micrograms/day subcutaneously was started. Twenty-four hours after the first administration the neutrophil counts began to rise, to 4389/microliters, with a maximum after the third administration and stabilizing at normal levels within 10 days. Since agranulocytosis is considered to be a severe and fatal complication of methimazole therapy, treatment with granulocyte colony stimulating factor seems to be useful for this life-threatening condition.

Genomic structure of the POU-related hepatic transcription factor HNF-1 alpha.

Hepatocyte Nuclear Factor-1 alpha (HNF-1 alpha) is a vertebrate transcriptional regulatory protein which plays a prominent role in the activation of a large family of hepatocyte-specific genes. It is the prototype of a new subfamily of POU-related proteins important in embryogenesis and cell-type specification. Here we report on the genomic structure and DNA sequence of HNF-1 alpha of the hen. Functional domains are non-uniformly conserved between hen and mammals consistent with the notion of functions in the hen oviduct that were lost in mammals after avian mammalian separation. The unusual homeo-related DNA-binding domain is well preserved between birds and mammals. The exon/intron pattern of the gene changed during evolution. The rat gene consists of 9 exons, the chicken gene of 10. In mammals one intron was eliminated that in hens subdivides the serine-rich transactivation domain. Comparison of the sequences at this junction indicates the involvement of elements of the V(D)J recombination system in the process of intron elimination.

Hepatic nuclear factor 1 alpha (HNF-1 alpha) is expressed in the oviduct of hens and interacts with regulatory elements of the lysozyme gene.

HNF-1 alpha is a nuclear transcriptional regulatory protein required for the expression of a variety of liver-specific genes. This factor was previously considered liver-specific but later shown to be expressed also in a few other mammalian tissues. Here we report on the occurrence of HNF-1 alpha in the avian oviduct. This finding is of particular interest because HNF-1 alpha is not expressed in female reproductive organs of mammals. The avian oviduct is the site of assembly for the avian egg and the site of tissue-specific synthesis of the major egg white proteins, such as lysozyme. We also demonstrate that the chicken lysozyme gene contains HNF-1 recognition sites within two of its important upstream regulatory elements. The presence of HNF-1 recognition elements in functionally significant regulatory sites of the lysozyme gene and high levels of HNF-1 alpha in the oviduct is a strong indication for the involvement of HNF-1 alpha in the control of the lysozyme gene and possibly other egg white protein genes in the chicken oviduct. Apparently, HNF-1 alpha performs functions in the avian oviduct that were lost upon development from birds to mammals.