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PubMed2003

Hyperkeratosis and leukocytosis in transgenic mice carrying MHC class I chain-related gene B (MICB).

Major histocompatibility complex (MHC) class I chain-related gene A and B (MICA and MICB) are located very close to HLA-B. MICA is reported to be strongly associated with Behçet's disease (BD), a multisysytemic inflammation disorder characterized by oral apthous ulcers, skin lesions and genital ulcers. These two molecules are highly conserved at the amino acid levels. To determine the function of MICB in vivo and the relationship between the expression of MICB and BD experimentally, we produced several transgenic mouse lines (termed CAG-MICB) expressing human MICB cDNA under a ubiquitous promoter. They exhibited a 50% increase in the number of white blood cells compared with their non-transgenic littermates, and also exhibited a 10-20% reduction in body weight compared with non-transgenic littermates. Exfoliation of the skin first appeared around 7 days after birth and disappeared after 2 weeks of age. This was repeatedly observed in the transgenic offspring of two independent CAG-MICB lines examined. Histopathological analysis of skin of young mice exhibiting skin abnormalities revealed hyperkeratosis of the epidermis and thickening of the granular layer with slight infiltration of inflammatory cells in the dermis without any vasculitis. Other remarkable abnormalities associated with BD have not been observed in the CAG-MICB lines. Furthermore, fluorescein angiography of eyes of the CAG-MICB lines was performed, but there were no marked changes of BD-related uveitis in the ocular fundus. These findings suggest that (i) MICB expression is related to temporary skin inflammation, and (ii) expression of MICB is not directly associated with BD.

Animals↗
PubMed1997

Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho).

FLT3 is a member of receptor tyrosine kinases expressed in leukemia cells, as well as in hematopoietic stem cells. Recently, a somatic alteration of the FLT3 gene was found in acute myeloid leukemia, as an internal tandem duplication (FLT3/ITD) which caused elongation of the juxtamembrane (JM) domain of FLT3. Here we characterized the FLT3/ITD and investigated its clinical significance in acute promyelocytic leukemia (APL). Seventy-four newly diagnosed patients with APL, who were treated with the same protocol in a multi-institutional study, were studied for the FLT3/ITD. Genomic and message sequences of the FLT3 gene were amplified by means of polymerase chain reaction (PCR), and elongated PCR products were sequenced. Fifteen patients (20.3%) had FLT3/ITD, all of which were transcribed in frame. Location of the duplicated fragments (six to 30 amino acids) varied from patient to patient. However, they always contained either Y591 or Y599, but the tyrosine kinase domain was not significantly affected. This finding implied that signal transduction of FLT3 is amplified by the duplication. Clinically, the presence of FLT3/ITD was related to high peripheral white blood cell counts as well as peripheral leukemia cell counts (P < 0.0001), high LDH level (P = 0.04), and low fibrinogen concentration (P = 0.04). These data suggest that FLT3/ITD plays a significant role in progression of APL.

Adult↗
PubMed2003

Plasma level of tumor necrosis factor-alpha (TNF-alpha) correlates with leukocytosis and biological features of leukemic cells, but not treatment response of children with acute lymphoblastic leukemia.

We have analyzed the clinical significance of the plasma level of tumor necrosis-alpha (TNF-alpha) detection in childhood acute lymphoblastic leukemia (ALL) at diagnosis. 49 patients (pts) with B-lineage ALL (3-17 years of age) and 30 healthy children (age-related control) were enrolled in study. The mean value of the level of TNF-alpha was 43.4 +/- 8.1 pg/ml in ALL pts and 30.7 +/- 3 pg/ml in control. In ALL pts the level of TNF-alpha positively correlated with blast cell count in peripheral blood (R = +0.432; P = 0.008); negatively correlated with percentages of S-phase leukemic cells (R = -0.446; P = 0.042) and culture-induced apoptotic cells (R = -0.411; P = 0.057). Pts with TNF-alpha level above the median value were characterized by higher WBC count (P = 0.025), lower percentage of S-phase leukemic cells (P = 0.02) and tendency to lower percentage of apoptotic cells (P = 0.07) vs pts with TNF-alpha level below the median value. No significant association of the level of TNF-alpha with treatment response at days 8 and 15 or 3-year overall survival was defined. We conclude that the elevated plasma level of TNF-alpha is a useful marker to assess disease activity/progression, but not prognosis of childhood B-lineage ALL.

Adolescent↗
PubMed1967

Studies on the leukocytosis and lymphocytosis induced by Bordetella pertussis. II. The effect of pertussis vaccine on the thoracic duct lymph and lymphocytes of mice.

The 24 hr volume flow, cell concentration, and total cell output of thoracic duct fluid from mice with pertussis-induced hyperlymphocytosis were markedly reduced when compared with values obtained in normal animals. An increase in the number of circulating lymphocytes occurred in several of the pertussis-treated mice despite the presence of an indwelling thoracic duct cannula. The drainage from such animals also showed a reduced cell concentration and total cell output. It is suggested that lymphocyte recirculation may be minimal in pertussis-induced lymphocytosis, and the evidence obtained also suggests that lymphocytes may enter the blood stream by direct routes during the course of the reaction.

Animals↗