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

Particulate glucan (P) but not soluble glucan (F) has been shown to sensitize rats to endotoxins. This phenomenon is believed to be mediated by the reticuloendothelial system (RES). The effect of glucan-P and -F on the RES, and the response of glucan-treated rats to nonlethal doses of endotoxin were investigated. Rats were injected for 5 days with 10 mg/kg of glucan-P, -F or saline. Three days later rats were either (1) injected with colloidal carbon for clearance studies, (2) sacrificed for organ histology and determination of serum glucose, plasma thromboxane (Tx) B2, and plasma 6-keto-prostaglandin (PG) F1 alpha concentrations, or (3) challenged with a nonlethal dose of endotoxin. The latter were further subdivided into groups for either 30-day survival or for sacrifice at 30 min or 4 h post-endotoxin infusion to obtain blood samples for glucose, TxB2, and 6-keto-PGE1 alpha determinations. Glucan-P induced hepatosplenomegaly and granulomatous changes within the liver and spleen. The carbon clearance halftime was markedly decreased in these animals. In glucan-P-treated rats challenged with endotoxin, elevated concentrations of both plasma prostanoids were observed as well as alterations in serum glucose levels. These changes were less pronounced in glucan-F- or saline- treated rats. Following endotoxin challenge, only 40% of glucan-P-treated rats survived 30 days whereas 100% of both the glucan-F and saline-treated rats survived. We conclude that glucan-P, in contrast to glucan-F, significantly heightens RES function and that this effect likely accounts for the endotoxin sensitivity.
 ...
PMID:A comparative evaluation of particulate and soluble glucan in an endotoxin model. 352 32

A soluble form of the reticuloendothelial- and immune modulating agent glucan (glucan-F) has been evaluated for its effects on hemopoiesis. A single 5.0 mg intravenous injection of glucan-F into C3H/HeN mice increased peripheral white blood cellularity, bone marrow and splenic cellularity, bone marrow and splenic granulocyte-macrophage progenitor cell numbers (GM-CFC), and splenic pluripotent stem cell (CFU-s) and erythroid progenitor cell (CFU-e) numbers. Serum levels of granulocyte-macrophage colony stimulating activity (CSA) were also elevated following glucan-F administration. These hemopoietic responses correlate well with those previously shown to be induced by intravenous administration of particulate glucan (glucan-P). In contrast to glucan-P, however, intravenous glucan-F administration has been shown not to induce granuloma formation and severe hepatosplenomegaly, thus the potential clinical use of glucan-F as a hemopoietic stimulant is more likely than that of glucan-P.
 ...
PMID:Hemopoietic effects of intravenous soluble glucan administration. 376 May 93

A soluble derivative of particulate glucan was prepared and evaluated for its antitumor and antibacterial activity. Intravenous administration of soluble or particulate glucan resulted in significant reduction in the growth of a syngeneic anaplastic mammary carcinoma and melanoma B16 and enhanced survival. Soluble and particulate glucan also significantly enhanced survival of mice infected with Staphylococcus aureus. Hepatosplenomegaly and granuloma formation observed in particulate glucan-treated mice were not observed in the soluble glucan group. It is evident that the soluble glucan initiates significant antitumor and antistaphylococcal activity. The active soluble fraction of particulate glucan may be preferable to particulate glucan in view of inherent facility of parenteral administration.
 ...
PMID:Comparative evaluation of the tumor inhibitory and antibacterial activity of solubilized and particulate glucan. 723 29

The classic clinical presentation for type IV glycogen storage disease (branching enzyme deficiency, GSD IV) is hepatosplenomegaly with failure to thrive occurring in the first 18 months of life, followed by progressive liver failure and death by age 5 years. Although there have been two patients without apparent liver progression previously reported, no long-term follow-up clinical data have been available. We present here the clinical spectrum of the non-progressive liver form of GSD IV in four patients, and long-term follow-up of the oldest identified patients (ages 13 and 20 years). None has developed progressive liver cirrhosis, skeletal muscle, cardiac or neurological involvement, and none has been transplanted. Branching enzyme activity was also measured in cultured skin fibroblasts from patients with the classic liver progressive, the early neonatal fatal, and the non-progressive hepatic presentations of GSD IV. The residual branching enzyme activity in the patients without progression was not distinguishable from the other forms and could not be used to predict the clinical course. Our data indicate that GSD IV does not always necessitate hepatic transplantation and that caution should be used when counselling patients regarding the prognosis of GSD IV. Patients should be carefully monitored for evidence of progression before recommending liver transplantation.
 ...
PMID:Clinical and laboratory findings in four patients with the non-progressive hepatic form of type IV glycogen storage disease. 883 Jan 77

Relatively high doses of the soluble form of fungal glucan (50 mg/kg of body weight) were administered to two clinically healthy calves. Hepatosplenomegaly was not observed. Quantitative and significant qualitative changes were seen in macrophages in the medulla of lymph nodes as compared to the control animals. Both the fibrillar and the granular components in the vacuoles of phagocytosing cells appeared to be positive in the periodic acid-Schiff reaction (PAS); an amorphous component was PAS negative. Quantitative changes occurred also in the expression of IgM molecules on the surface of B lymphocytes. The results indicate that glucan can be used in ruminants also in a single high dose.
 ...
PMID:Tissue macrophages of calves after high doses of glucan. 890 41

Glycogen storage disease type IV (GSD-IV) is a rare autosomal recessive disease caused by deficient glycogen branching enzyme (GBE). We report a 15-month-old female patient with GSD-IV who exhibited an abdominal distension and failure to thrive for 9 months. The patient showed hepatosplenomegaly with massive ascites. The laboratory findings showed abnormal liver functions including prolongation of prothrombin time and partial thromboplastin time. The light microscopic and electron microscopic findings of the liver biopsy specimen were consistent with GSD-IV. Measurement of glycogen quantity in the red blood cells showed increased storage of glycogen in the patient and interestingly, in her mother. The GBE activity of the patient's red blood cells was undetectable. The patient's ascites, general condition, and laboratory findings have been improved with supportive treatment with diuretics and a low dose of prednisolone.
 ...
PMID:Glycogen storage disease type IV: a case report. 961 Jun 25

Glycogen storage disease type IV (GSD-IV) is a rare autosomal recessive disease caused by a deficiency of glycogen branching enzyme (GBE) activity. This results in the accumulation of abnormal glycogen in the liver and other organs. We report the case of a 14-month-old female patient with typical hepatic pathologic findings of GSD-IV. The patient suffered from decreased muscle tone and progressive hepatosplenomegaly since birth. A wedge biopsy of the liver showed enlarged hepatocytes with colorless to faintly eosinophilic ground glass intracytoplasmic inclusions. Portal fibrosis and lobular, fibrous septa were present. Ultrastructure of the inclusions revealed non-membrane-bound fibrillar material 5 nm in maximal diameter. Enzyme study revealed a total deficiency of GBE activity.
 ...
PMID:Glycogen storage disease type IV: a case report. 1053 7

Glycogen storage disease type IV (GSD IV; Andersen disease) is caused by a deficiency of glycogen branching enzyme (GBE), leading to excessive deposition of structurally abnormal, amylopectin-like glycogen in affected tissues. The accumulated glycogen lacks multiple branch points and thus has longer outer branches and poor solubility, causing irreversible tissue and organ damage. Although classic GSD IV presents with early onset of hepatosplenomegaly with progressive liver cirrhosis, GSD IV exhibits extensive clinical heterogeneity with respect to age at onset and variability in pattern and extent of organ and tissue involvement. With the advent of cloning and determination of the genomic structure of the human GBE gene (GBE1), molecular analysis and characterization of underlying disease-causing mutations is now possible. A variety of disease-causing mutations have been identified in the GBE1 gene in GSD IV patients, many of whom presented with diverse clinical phenotypes. Detailed biochemical and genetic analyses of three unrelated patients suspected to have GSD IV are presented here. Two novel missense mutations (p.Met495Thr and p.Pro552Leu) and a novel 1-bp deletion mutation (c.1999delA) were identified. A variety of mutations in GBE1 have been previously reported, including missense and nonsense mutations, nucleotide deletions and insertions, and donor and acceptor splice-site mutations. Mutation analysis is useful in confirming the diagnosis of GSD IV--especially when higher residual GBE enzyme activity levels are seen and enzyme analysis is not definitive--and allows for further determination of potential genotype/phenotype correlations in this disease.
 ...
PMID:Glycogen storage disease type IV: novel mutations and molecular characterization of a heterogeneous disorder. 2005 79