Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 2-month-old male Tongan infant presented with fever, severe skin and mucosal infections, hepatosplenomegaly, thrombocytopenia, and normal neutrophil counts. While polymorphonuclear neutrophil (PMN) morphology was normal, several neutrophil motile functions were found to be altered in the patient. Furthermore, two siblings had died in infancy with a similar clinical picture, raising the possibility of an inherited neutrophil defect. Random migration and chemotaxis, assessed by the under agarose method, were profoundly impaired. Actin polymerization, as measured by flow cytometry of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phallacidin (NBD-phallacidin)-stained PMNs, showed lower basal F-actin and a 1.75-fold increase in response to 10(-7) mol/L formyl-methionyl-leucyl-phenylalanine (FMLP) compared with a 4.51-fold increase in control. Microscopic examination of NBD-phallacidin-stained PMN spread on glass showed decreased area of spreading and F-actin-rich filamentous projections distinct from control. The early phase of FMLP-induced right angle light scattering was absent, similar to the effect caused by cytochalasin-B (CB), an inhibitor of actin polymerization. Accordingly, FMLP induced secretion of elastase without the addition of CB. Staphylococcus aureus killing was 50% of control whereas superoxide production response to FMLP and surface expression of CD11b were greater than twice normal. Partial defects in actin polymerization and scatter were seen in the parents and release of elastase, in the absence of CB, was also increased in both parents. Sodium dodecyl sulfate-polyacrylamide electrophoresis of whole cell proteins from the patient showed a marked decrease in an 89-Kd protein (8% of control) and a marked increase in a 47-Kd protein (4.2-fold). Both mother and father had decreased 89-Kd (77% and 42% of control) and increased 47-Kd proteins (2- and 3.4-fold), although neither had recurrent infections or chemotactic defects. These studies describe a new inherited actin dysfunction syndrome associated with severe propensity to fungal infection and draw attention to the proteins of apparent molecular weights of 89 Kd and 47 Kd, which may be of great importance in the regulation of actin polymerization in human PMNs.
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PMID:An inherited defect of neutrophil motility and microfilamentous cytoskeleton associated with abnormalities in 47-Kd and 89-Kd proteins. 187 95

A 9-year-old girl was admitted to Mie University Hospital June 25, 1992, complaining of fever, skin rash and pallor. Physical examination revealed anemia and hepatosplenomegaly. Laboratory findings showed normocytic normochromic anemia, increased reticulocyte counts and remarkably decreased haptoglobin level. Red blood cells had no morphological abnormality. Bone marrow examination showed erythroid hyperplasia without abnormal cells. Hemoglobin electrophoresis showed an abnormal band. The amino acid structure and sequence of the abnormal hemoglobin was determined to be an unstable hemoglobin, Hb Buenos Aires [beta 85 (F1) Phe-->Ser]. Sequence of genomic DNA and cDNA was compatible to Hb Buenos Aires. Parvovirus B19 infection was thought to have caused severe anemia due to hemolytic crisis in this patient because its IgM antibody was positive on admission. She recovered soon without any treatment and has been followed in the outpatient clinic. Her parents and brother showed no hemoglobin abnormality.
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PMID:[The first case in Japan of unstable hemoglobin, Hb Buenos Aires [beta 85 (F1) Phe-->Ser], with parvovirus B19 infection (first case in Japan)]. 858 69

A female infant with hypoproteinemia and coagulopathy associated with hypertyrosinemia was successfully treated with living-related liver transplantation (LRLT). On the 12th day of life plasma amino acid analysis revealed a marked elevation of tyrosine, so the patient was fed on a low-tyrosine and low-phenylalanine diet. However, hepatosplenomegaly, hypotonia, alopecia, eczema and psychomotor delay did not improve and recurrent episodes of disseminated intravascular coagulation (DIC) caused her condition to deteriorate. Liver biopsy on the 230th day revealed marked fatty change accompanied by mild to moderate cholestasis. Therefore, LRLT from her father was performed on the 286th day resulting in improvement of all the aforementioned signs and symptoms. Despite a thorough examination, no diagnosis of a known disorder could be established. However, her elder brother had also been born with severe hypoproteinemia and coagulopathy, and died of DIC on the second day of life. Thus, the disorder is designated as a new entity, namely 'congenital hypoproteinemia and coagulopathy associated with hypertyrosinemia'.
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PMID:Liver transplantation in a case of hypoproteinemia and coagulopathy. 958 13

Hemoglobin Hammersmith, a rare, unstable hemoglobin variant, was diagnosed in a 9-year-old Japanese girl. She presented with the typical manifestations of this disorder, including neonatal hyperbilirubinemia, followed by progressive hepatosplenomegaly, jaundice, and bilirubinuria. Because of severe hemolytic anemia, she received transfusions of red blood cells every 3 to 4 weeks. However, she underwent splenectomy at the age of 4 years and has continued to be in partial remission without requiring further transfusions. DNA sequence analysis of the polymerase chain reaction-amplified beta-globin gene revealed a point mutation (T --> C) in the second nucleotide of the 42nd codon of the beta-globin chain (beta 42(CD1) Phe --> Ser).
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PMID:Hemoglobin Hammersmith [beta 42(CD1) Phe --> Ser] causing severe hemolytic anemia in a Japanese girl. 1661 20

Clinical manifestations of Niemann-Pick type C1 (NP-C1) disease include neonatal hepatosplenomegaly and in some patients progressive liver dysfunction and failure. This study involved a 1H NMR-linked metabolomics analysis of liver samples collected from a NP-C1 disease mutant mouse model in order to explore time-dependent imbalances in metabolic pathways associated with NP-C1 liver dysfunction, including fibrosis. NP-C1 mutant (Npc1-/-; NP-C1), control (Npc1+/+; WT), and NP-C1 heterozygous mice (Npc1+/-; HET) were generated from heterozygote matings. Aqueous extracts of these liver samples collected at time points of 3, 6, 9, and 11 weeks were subjected to high-resolution NMR analysis, and multivariate (MV) metabolomics analyses of data sets acquired were performed. A MV random forests (RFs) model effectively discriminated between NP-C1 and a combined WT/HET hepatic NMR profiles with very high predictive accuracy and reliability. Key distinguishing features included significant upregulations in the hepatic concentrations of phenylalanine, tyrosine, glutamate, lysine/ornithine, valine, threonine, and hypotaurine/methionine, and diminished levels of nicotinate/niacinamide, inosine, phosphoenolpyruvate, and 3-hydroxyphenylacetate. Quantitative pathway topological analysis confirmed that imbalances in tyrosine biosynthesis, and hepatic phenylalanine, tyrosine, glutamate/glutamine, and nicotinate/niacinamide metabolism were involved in the pathogenesis of NP-C1 disease-associated liver dysfunction/damage. 1H NMR-linked metabolomics analysis provides valuable biomarker information regarding hepatic dysfunction or damage in NP-C1 disease.
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PMID:1H NMR-Linked Metabolomics Analysis of Liver from a Mouse Model of NP-C1 Disease. 2750 74