Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From 1969--1975 patients with predominantly megakaryocytic myelosis were observed. Diagnosis was made up after histologic examination of iliac crest bone biopsy specimens embedded in methacrylate. From 6 patients rebiopsies and from further eleven ones the removed spleens were available. Autopsy was performed in 12 cases. In our material predominantly megakaryocytic myelosis was especially observed in male patients of advanced ages. The course of the disease was rarely acute, most often chronic and associated with the development of an extreme splenomegaly. Transition into osteomyelofibrosis or osteomyelosclerosis was frequent, the latter condition tended to develop a so-called myelosarcoma. The cause of death often was a generalized hemorrhagic diathesis with gastrointestinal hemorrhage or an fatal infection.
 ...
PMID:[Pathologc findings in megakaryocytic myelosis (author's transl)]. 89 19

In planning the treatment of splenomegaly in primary or secondary osteomyelofibrosis it is necessary to know whether there is any significant hematopoiesis outside the spleen. In contrast to the measurement of iron kinetics with 59Fe, which is not suitable for imaging, immunoscintigraphy with the monoclonal antibody Bw 250/183 allows specific imaging of the hematopoietic bone marrow. The diagnostic use of this method in addition to iron kinetics is illustrated and discussed in a patient with primary osteomyelofibrosis.
 ...
PMID:[Immunoscintigraphy of the hematopoietic bone marrow in osteomyelofibrosis]. 221 13

Histomorphometry was performed on representative trephine biopsies of the bone marrow on admission of 50 patients (21 male, 29 female - age 67 years) with so-called primary osteomyelofibrosis/-sclerosis (OMF) not preceded by any other subtype of chronic myeloproliferative disorders. This study was firstly aimed at testing correlations between histological features (amount of haematopoiesis, cytological aspects of megakaryocytes, density of reticulin and collagen fibres and degree of osteosclerosis) and laboratory data, as well as spleen size and duration of relevant prediagnostic symptoms. Secondly, we concentrated on a discrimination of OMF patients into two subgroups according to bone marrow morphology and clinical variables. Statistical evaluation of histomorphometric variables and haematological findings disclosed that there was a progressive fibro-osteosclerotic process in the evolution of disease features. Increase in medullary fibrosis was significantly paralleled by an abnormal or pleomorphic megakaryopoiesis in the bone marrow: there was an increase in irregularity of perimeters for megakaryocytes and naked nuclei combined with smaller sizes of these elements including the nuclei. Additionally, there was a greater number of pycnotic bare nuclei. A number of morphometric features (density of fibres, degree of osteosclerosis, amount of haematopoiesis) were associated with corresponding clinical data (spleen size, length of preclinical history). By consideration of a set of basic histomorphometric variables our cohort of 50 patients could be divided into an early hyperplastic subtype with no or minimal medullary reticulin and another group with conspicuous fibrotic and osteosclerotic alterations of the bone marrow. It was noticeable that we found no significant correlation between amount of haematopoiesis or marrow cellularity with splenomegaly. This result suggests that splenic haematopoiesis (myeloid metaplasia) may represent an autonomous or neoplastic process and not only compensation for a failing fibro-osteosclerotic bone marrow.
 ...
PMID:Histomorphometry of bone marrow biopsies in primary osteomyelofibrosis/-sclerosis (agnogenic myeloid metaplasia)--correlations between clinical and morphological features. 250 23

Ingestion rate of granulocytes in osteomyelofibrosis with splenomegaly, which is still a matter of controversy, was measured in 32 patients. The mean ingestion rate in patients' granulocytes was similar to that of the controls; the results, however, were more dispersed in the patients than in the controls, with very high (three patients) and very low (three patients) ingestion rates. Ingestion alterations were serum-independent. Neutrophil glycolytic enzymes and adenylate-kinase were measured in order to assess: (1) if they could be responsible for the observed abnormalities and (2) if enzyme abnormalities, previously described in red blood cells, also occur in the neutrophils. Major increases in phosphofructoaldolase and in 3-phosphoglycerate kinase activities, contrasting with a decrease in pyruvate kinase activity were observed. These, however, did not correlate with ingestion alterations. In conclusion, we showed that the granulocyte ingestion rate is altered in a few patients only, that the alterations are unrelated to the serum, to adenylate kinase or to glycolytic enzyme abnormalities. The latter, however, are important. The mechanisms of their occurrence are unknown and hypotheses such as those proposed for red blood cells enzyme modifications in myeloproliferative disorders could be applicable.
 ...
PMID:Ingestion rate and glycolytic enzymes in neutrophils of patients with agnogenic osteomyelofibrosis and splenomegaly. 671 65

Osteomyelofibrosis is a myeloproliferative disorder in which fibrosis and sclerosis finally lead to bone marrow obliteration. Liver and spleen compensate for bone marrow loss with extramedullary hematopoiesis. In some patients the resulting splenomegaly causes severe symptoms such as local compression, thrombocytopenia and hemolytic anemia. In such patients, splenectomy is the only promising treatment, although it represents a significant risk.
 ...
PMID:[Splenectomy in osteomyelofibrosis. Indications and outcome]. 901 20

Using a new adenoviral vector (Ad) construct, we expressed human thrombopoietin (TPO) cDNA (AdTPO) in mice with various inherited immune deficiency syndromes such as nude, SCID and NOD-SCID mice. Immune normal Balb/c mice and a vector construct without TPOcDNA (AdNull), respectively, were used for controls. All animals (3 per group) were treated with a single application of 10(9) PFU (plaque forming unit) of Ad (AdTPO or AdNull) intraperitoneally on day 0. Four to 5 weeks following AdTPO administration, SCID and NOD-SCID mice demonstrated peak concentration of PLT of 12- to 14-fold normal value simultaneously with maximum concentration of PMNs (10- to 12-fold normal value). Later on these animals had a chronic thrombocytosis. In contrast, Balb/c mice and nude mice experienced PLT peak concentration of 4- to 6-fold normal value without granulocytosis 1 to 2 weeks following AdTPO treatment. Only nude mice had chronically elevated PLTs. In contrast, Balb/c mice developed thrombocytopenia due to cross-reacting anti-TPO antibodies. Animals with chronic thrombocytosis revealed increased content of CFU-G/GM, CFU-GEMM and CFU-Meg in bone marrow compared with controls. In contrast, Balb/c mice showed decreased content of CFUs if anti-TPO-antibodies were present. Histologically, only SCID mice developed severe osteomyelofibrosis and osteomyelosclerosis, hepato-splenomegaly, extramedullary hematopoiesis in liver and lung and ultimately suffered of progressive pancytopenia, anisocytosis, fragmentocytosis and a lethal wasting syndrome. In contrast, NOD-SCID mice which demonstrated similar extent of TPO overexpression and in addition to the B- and T-cellular immune deficiency harbour defective monocytes and macrophages, did not develop fibrotic changes of the bone marrow. From these results, we conclude (1) chronic TPO overexpression in vivo may lead to thrombocytosis and granulocytosis with expansion of CFU-GM, -GEMM and -Meg; (2) in vivo expression of adenovirally mediated TPOcDNA depends on immune competency of the host; (3) functionally normal monocytes and macrophages are indispensable for development of secondary osteomyelofibrosis and (4) adenovirally mediated expression of xenogeneic transgenes may brake immune tolerance for the respective self protein leading to autoimmune phenomena. Our in vivo model might provide further insights into the pathophysiology of secondary osteomyelofibrosis and may prove useful in designing new strategies for immune therapies of cancer.
 ...
PMID:[Adenovirus long-term expression of thrombopoietin in vivo: a new model for myeloproliferative syndrome and osteomyelofibrosis]. 982 87