Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A morphometric analysis of bone marrow biopsy specimens from patients with myelofibrosis was made to determine the amount of lattice fiber and the number of megakaryocytes, to compare the degree of myelofibrosis in primary and secondary myelofibrosis, and to assess the relationship between the morphometric findings and other parameters. Eight patients with agnogenic myeloid metaplasia (AMM) and six with chronic myelogenous leukemia associated with frank myelofibrosis (CML-MF) were studied. When the main clinical, hematological, and laboratory features of both groups of patients were compared, the only significant difference was in the neutrophil alkaline phosphatase score. Morphometric study showed that the amount of lattice fiber and the number of megakaryocytes in AMM were not statistically different from those in CML-MF, and that neither the number of megakaryocytes nor the platelet count correlated with the amount of lattice fiber.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Morphometric analysis of myelofibrosis in agnogenic myeloid metaplasia and chronic myelogenous leukemia. 168 56

A morphometric analysis was performed on trephine biopsies of the bone marrow to identify atypical megakaryocyte proliferation following PAS staining and the immunohistological demonstration of factor VIII. This study includes nine patients with a megakaryoblastic crisis in chronic myeloid leukemia (CML), four with acute megakaryoblastic leukemia (AM) and three with myeloid dysplasia later evolving into overt acute leukemia. Comparison and statistical evaluation of the PAS reaction with anti-factor VIII staining reveals that the latter technique not only facilitates the recognition of immature and abnormal megakaryocytes, but leads to a significantly increased count for all megakaryocytic elements in the bone marrow. Thus our retrospective investigation of routinely processed and paraffin-embedded trephine biopsies shows that the diagnosis of a megakaryoblastic crisis in CML as well as AM may be easily established with the aid of the anti-factor VIII method. In all cases of megakaryoblastic proliferation in CML and AM, the appearance of blasts was associated with moderate to pronounced myelofibrosis which could be also determined by morphometry.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:The use of the anti-factor VIII method on trephine biopsies of the bone marrow for the identification of immature and atypical megakaryocytes in myeloproliferative diseases and allied disorders. A morphometric study. 289 11

A planimetric study of megakaryopoiesis in various chronic myeloproliferative diseases (CMPD) was performed and the results compared with those from controls and myelitis of rheumatic origin. Morphometric measurements included at least 200 megakaryocytes in each case observed in Giemsa-stained semithin sections of resin-embedded core biopsies. Twenty specimens were evaluated from the controls and inflammatory disorders and from each of the following CMPD: 1, chronic granulocytic leukaemia (CGL); 2, polycythaemia vera (P. vera); 3, chronic megakaryocytic-granulocytic myelosis without or with minimal increase in reticulin fibre content (CMGM); 4, myelofibrosis or osteomyelosclerosis (MF/OMS). Megakaryocytes were classified as follows: 1, normal megakaryocytes at all stages of maturation; 2, giant forms; 3, microforms; 4, intussusceptions; 5, a-nuclear cytoplasmic fragments; 6, naked nuclei or necrotic forms. The results of this study demonstrate obvious abnormalities of megakaryopoiesis in addition to the increase in absolute numbers of megakaryocytes per marrow area and their different sizes as reported earlier (Thiele et al. 1982). Aberrations are particularly conspicuous when pure granulocytic proliferation or neoplasia of CGL is compared with the so-called mixed cellularity of megakaryocytes and granulocytes in CMGM including MF/OMS. Abnormalities of the giant forms of megakaryocytes are especially evident and comprise irregular cellular and nuclear perimeters (as calculated by a modified shape factor) in the two latter entities (CMGM-MF/OMS). This remarkable feature is associated with a disorganization of nuclear development and/or a disproportionate nuclear-cytoplasmic ratio which has never been observed in CGL previously. In combination with this striking cellular anomaly, which is compatible with an extreme amoeboid shape of giant forms in CMGM and MF, intussuceptions and a-nuclear cytoplasmic fragments are frequently encountered. The final stage of megakaryopoiesis, i.e. naked nuclei, are increased in number in all CMPD, probably because of enhanced proliferation and platelet shedding. Naked nuclei are often small in CGL (as remnants of the frequent micromegakaryocytes) and large in P. vera and CMGM/MF (depending on the high incidence of giant megakaryocytes in these latter disorders).
Virchows Arch B Cell Pathol Incl Mol Pathol 1982
PMID:Abnormalities of megakaryocytes in myelitis and chronic myeloproliferative diseases. 613 85

The reliability of histopathological diagnosis in bone marrow specimens from patients with chronic myeloproliferative disorders (CMPD) was evaluated by correlating the histological findings with molecular genetic and cytogenetic analyses of the Ph1-translocation. A rearrangement of m-bcr was detected only in patients (28/30) diagnosed histologically as chronic myeloid leukemia (CML). This finding was supported by the presence of a Ph1-chromosome in 24/26 patients with CML examined. All the patients with other types of CMPD, including polycythemia vera (PV), primary thrombocythemia (PTH) and chronic megakaryocytic-granulocytic myelosis (CMGM), as well as those with unclassifiable CMPD (CMPD.UC) were Ph1-negative (n = 38). The histopathological discrimination of CML from Ph1-negative varieties of CMPD was also reliable for patients with myelofibrosis complicating CML, CMGM and CMPD.UC. The results demonstrate that bone marrow histopathology allows a reliable diagnosis of CML. This is in contrast with hematological data such as high platelet counts which show considerable overlapping in the various forms of CMPD.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Evidence from molecular genetic and cytogenetic analyses that bone marrow histopathology is reliable in the diagnosis of chronic myeloproliferative disorders. 809 57

The newly cloned gene Spin encodes a 30-kDa protein, a well-defined abundant molecule found in mouse oocytes and early embryos. This protein SPIN undergoes metaphase-specific phosphorylation and binds to the spindle. To understand the role of SPIN in oocyte meiosis, oocytes were treated with drugs that affect the cell cycle by activating or inactivating specific kinases. The posttranslational modification of SPIN in the treated oocytes was then investigated by one- and two-dimensional gel electrophoresis. Modification of SPIN is inhibited by treatment with 6-dimethylaminopurine (DMAP), suggesting that SPIN is phosphorylated by a serine-threonine kinase. Furthermore, SPIN from cycloheximide-treated oocytes that lack detectable MAP kinase activity is only partially phosphorylated, indicating that SPIN may be phosphorylated by the MOS/MAP kinase pathway. To confirm this observation, SPIN was analyzed in Mos-null mutant mice lacking MAP kinase activity. Normal posttranslational modification of SPIN did not occur in Mos-null mutant oocytes. In addition, there is reduced association of SPIN with the metaphase I spindle in Mos-null mutant oocytes, as determined by immunohistochemical analysis. These findings suggest that SPIN is a substrate in the MOS/ MAP kinase pathway and further that this phosphorylation of SPIN may be essential for its interaction with the spindle.
Mol Reprod Dev 1998 Jun
PMID:SPIN, a substrate in the MAP kinase pathway in mouse oocytes. 959 May 41

Fully grown oocytes of most laboratory mice progress without interruption from the germinal vesicle (GV) stage to metaphase II, where meiosis is arrested until fertilization. In contrast, many oocytes of strain LT mice arrest precociously at metaphase I and often undergo subsequent spontaneous parthenogenetic activation. Cytostatic factor (CSF), which prevents the degradation of cyclin B and maintains high maturation-promoting factor (MPF) activity, is required for maintenance of metaphase I-arrest in LT oocytes, similar to its requirement for maintaining metaphase II-arrest in normal oocytes. However, CSF does not instigate metaphase I-arrest since a temporary metaphase I-arrest occurs in MOS-null LT oocytes. This paper addresses the mechanism(s) that may instigate metaphase I-arrest and tests the hypothesis that there may be one or more defects in LT oocytes that delay their acquisition of competence to trigger the cascade of processes that normally drive entry into and progression through anaphase I. To test this hypothesis, MPF activity was artificially abrogated by treating oocytes with a general protein kinase inhibitor, 6-DMAP, at various times during the progression of meiosis I. This allowed a comparison of the time at which LT and normal oocytes become competent to undergo the metaphase I/anaphase transition even if oocytes were arrested at metaphase I when 6-DMAP-treatment was begun. There were no differences between LT and control oocytes in the kinetics of MPF suppression by 6-DMAP. However, it was found that LT oocytes do not acquire competence to undergo the metaphase I/anaphase transition in response to 6-DMAP until 50-60 min after normal oocytes. A similar delay was observed in strain CX8-4 oocytes, which also have a high incidence of metaphase I-arrest, but not in strain CX8-11 oocytes, which exhibit a low incidence of metaphase I-arrest. MOS-null LT oocytes also exhibit a delay in acquisition of competence to undergo the metaphase I/anaphase transition. Thus, a delay in competence to undergo the metaphase I/anaphase transition in response to 6-DMAP-treatment correlates with metaphase I-arrest. It is therefore hypothesized that the observed delay in acquisition of competence to enter anaphase I may instigate the sustained metaphase I-arrest in LT oocytes by allowing CSF activity to rise to a level that prevents cyclin B degradation and maintains high MPF activity before anaphase can be initiated by normal triggering mechanisms.
Mol Reprod Dev 1999 Nov
PMID:Analysis of the mechanism(s) of metaphase I-arrest in strain LT mouse oocytes: delay in the acquisition of competence to undergo the metaphase I/anaphase transition. 1049 53

Gray platelet syndrome (GPS) is a disorder characterized by thrombocytopenia and large platelets that lack alpha granules and their contents. We describe two siblings with GPS who are members of a Moslem Bedouin genetic isolate. The children, an 8-year-old girl and a 5-year-old boy, had characteristic pale blue platelets lacking alpha granules on electron microscopy. Platelet aggregation studies were normal. The girl underwent a bone marrow aspiration and biopsy which showed mild myelofibrosis and extensive emperipolesis, i.e., the passage of other hematopoietic cells through megakaryocytes. Both children lacked high-molecular-weight multimers of von Willebrand factor (vWF) and had reduced activity and antigens of vWf. Platelet activation was approximately normal when ADP was employed as agonist, but significantly impaired using the thrombin receptor-activating peptide (TRAP). These findings are explained in light of the mechanism of action of each agonist. In addition, we propose that the emperipolesis was caused by increased P-selectin in megakaryocytes, and resulted in release of fibroblastic growth factors, explaining the myelofibrosis. The detailed description of these cases provides a basis for future differentiation of the various types of GPS, and for our current attempts to isolate the gene causing GPS in this genetic isolate.
Mol Genet Metab 2001 Nov
PMID:A new genetic isolate of gray platelet syndrome (GPS): clinical, cellular, and hematologic characteristics. 1170 59

Standard treatment regimens for haematological malignancies include myeloablative chemoradiotherapy and subsequent rescue by stem cell transplantation. However, these treatment regimens have significant associated mortality and morbidity, and disease recurrence remains a problem. One alternative approach is the targeted delivery of radiotherapy to the marrow using a bone-seeking agent labelled with an appropriate radioisotope, with the aim of delivering a potentially ablative radiation dose to marrow while minimising non-haematological toxicity. Pharmacokinetics and radiation dosimetry for a commercial preparation of samarium-153 ethylene diamine tetramethylene phosphonate (EDTMP; Quadramet) were evaluated in 43 tracer (average dose 740 MBq) studies of 42 patients with haematological malignancies. Measurements of 24-h retention were also available following infusion of 18-48 GBq in 15 patients. Quadramet cleared rapidly from the tissue, with a median biological half-life of 1.4 h. Activity taken up by the skeleton was firmly bound, with activity decreasing according to physical half-life at 24 h in 29 of the 43 cases. The percentage activity retained in the skeleton at 24 h with tracer doses was high (62%+/-13%), although this decreased to approximately 30% with therapy infusions. Because of this decrease in retention, the maximum feasible therapy activity for this formulation of Quadramet is 35 GBq. Median absorbed marrow radiation dose was 0.78 Gy/GBq in tracer studies: the decreased retention at high activities means that this corresponds to a median dose of 12 Gy for 35 GBq administered activity. It is possible to use 24-h retention as a rough guide to marrow dose in individual patients. In tracer studies, median bladder radiation dose was 0.22 Gy/GBq and radiation dose to the liver was very conservatively estimated at 0.2 Gy/GBq. After therapy infusions of up to 50 GBq in 37 patients, non-haematopoietic toxicity was not seen in any patient. In addition, myelosuppression was achieved without evidence of myelofibrosis. The residual dose rate to marrow fell to a level acceptable for stem cell re-infusion by 2 weeks after administration.
Eur J Nucl Med Mol Imaging 2002 Nov
PMID:Dosimetry and toxicity of Quadramet for bone marrow ablation in multiple myeloma and other haematological malignancies. 1239 66

Xenopus Aurora-A (also known as Eg2) is a member of the Aurora family of mitotic serine/threonine kinases. In Xenopus oocytes, Aurora-A phosphorylates and activates a cytoplasmic mRNA polyadenylation factor (CPEB) and therefore plays a pivotal role in MOS translation. However, hyperphosphorylation and activation of Aurora-A appear to be dependent on maturation-promoting factor (MPF) activation. To resolve this apparent paradox, we generated a constitutively activated Aurora-A by engineering a myristylation signal at its N terminus. Injection of Myr-Aurora-A mRNA induced germinal vesicle breakdown (GVBD) with the concomitant activation of MOS, mitogen-activated protein kinase, and MPF. Myr-Aurora-A-injected oocytes, however, appeared to arrest in meiosis I with high MPF activity and highly condensed, metaphase-like chromosomes but no organized microtubule spindles. No degradation of CPEB or cyclin B2 was observed following GVBD in Myr-Aurora-A-injected oocytes. In the presence of progesterone, the endogenous Aurora-A became hyperphosphorylated and activated at the time of MPF activation. Following GVBD, Aurora-A was gradually dephosphorylated and inactivated before it was hyperphosphorylated and activated again. This biphasic pattern of Aurora-A activation mirrored that of MPF activation and hence may explain meiosis I arrest by the constitutively activated Myr-Aurora-A.
Mol Cell Biol 2003 Mar
PMID:Biphasic activation of Aurora-A kinase during the meiosis I- meiosis II transition in Xenopus oocytes. 1258 89

We describe our experience with intravenous immunoglobulin (IVIg) treatment in fibrotic conditions and our results and experience with the effect of IVIg therapy to prevent metastases in malignancy. We have delineated the mechanisms by which IVIg can affect atherosclerosis (i.e., effect on MMP-9, antiidiotypes to anti-OxLDL), which led to reduced atherosclerosis in animal models. The effect of IVIg on skin fibrosis was assessed in a murine model of scleroderma-like disease. Collagen expression was decreased in the skin of mice treated with mouse IVIg, associated with decreased type I collagen gene expression, and accompanied by inhibition of transforming growth factor (TGF)beta and interleukin (IL)-4 secretion by splenocytes. We also described a favorable response to IVIg treatment in patients with either systemic sclerosis or myelofibrosis. The administration of IVIg to mice inoculated with melanoma or sarcoma cells induced a statistically significant inhibition of metastatic lung foci and prolongation of survival time. IVIg was found to stimulate the production of IL-12, an anti-tumor and anti-angiogenic cytokine. Positive staining of the cytoplasm, cell membrane, and nuclear membrane of several types of malignant tumors by IVIg was immunohistochemically demonstrated.
Methods Mol Med 2005
PMID:Intravenous immunoglobulin treatment for fibrosis, atherosclerosis, and malignant conditions. 1558 34


1 2 3 4 5 Next >>