Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anaerobic diphtheroids possessing lympho-reticular stimulatory properties may differ considerably in their peptidoglycan composition. Spleen weight-increasing activity of strains directly parallels their antitumour properties. P. granulosum strains, inactive in assays for lympho-reticular stimulation, appear to have a higher cell wall alanine content than most of the P. acnes and P. avidum strains tested. Two P. acnes strains, however, had equivalently high alanine ratios and were stimulatory. The presence of galactose does not appear to be required for activity since P. acnes II strains which lack this sugar can be fully stimulatory. The existence of the species P. lymphophilum (Torrey) is further supported by the finding of two more serologically identical strains which do not cross react serologically with the other species in the group. These organisms are fully stimulatory but have lysine rather than DAP as their cell wall diamino acid.
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PMID:Comparative studies on the cell wall composition of some anaerobic coryneforms of varying lympho-reticular stimulatory activity. 60 97

Alglucerase is a mannose-terminated form of human placental glucocerebrosidase, developed to treat patients with Gaucher's disease. Functional glucocerebrosidase is deficient in Gaucher's disease, an autosomal recessive lipid storage disorder that affects people of all ethnic backgrounds, but has a higher incidence among East European Jews (Ashkenazim). Gaucher's disease manifests with hepatosplenomegaly, bleeding disorders and bone disease, with the more rare subtypes (types 2 and 3) featuring neurological dysfunction. Prior to the development of enzyme replacement therapy, treatment for Gaucher's disease was mainly symptomatic relief. Primary treatment with glucocerebrosidase focuses on removal of the lipid metabolite that causes the pathology. Because of the rarity of Gaucher's disease clinical trials are small, and much of the data investigating alglucerase therapy have been obtained from studies of patients with type 1 disease, the prevalent subtype. Nonetheless, after intravenous administration of alglucerase, improvements are evident within 6 months of therapy. Patients have increased haemoglobin levels and platelet counts, and decreased incidences of epistaxis and bruising. Spleen and liver size are reduced, and skeletal parameters improve. Children gain height and most patients receiving alglucerase therapy are able to resume work and daily activities. Alglucerase is well tolerated, with few mild adverse reactions reported. Although the pharmacokinetic and pharmacodynamic information for alglucerase is limited, its unequivocal efficacy justifies enzyme replacement therapy with this compound as first-line treatment for patients with Gaucher's disease, for whom treatment options are limited.
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PMID:Alglucerase. A review of its therapeutic use in Gaucher's disease. 137 12

A new method of labelling human RBCs with 99mTc by the use of Sn-alpha-D-glucose 1-phosphate (GP) is presented. It was tested for spleen imaging in 16 normal volunteers. The labelling was carried out during the heating (30 min at 49.5 degrees C) to damage the cells and cooling (10 min at R.T.) steps. The labelling efficiency was 95.5 +/- 1.5% with Sn-GP and was better than Sn-PYP (61.5 +/- 25.0%). The radioactivity retention of RBCs was greater than 96% after 6 washings. The spleen was delineated very well in all the subjects. The spleen activity reached a plateau at 20 min post-injection. Spleen-to-liver and spleen-to-cardiac blood pool concentration ratios were high (10.4 +/- 2.2 and 10.1 +/- 3.2, respectively) calculated at 30 min. The method is simple, rapid and efficient.
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PMID:A simple and efficient method of labelling RBCs with 99mTc for spleen imaging. 234 Dec 90

The initial plasma clearance and organ distribution of alpha 1-acid glycoprotein and alpha 2-macroglobulin carrying different types of oligosaccharide, side chains was studied in rats. The differently glycosylated proteins were synthesized by rat hepatocytes in culture in the presence of tunicamycin (unglycosylated form), swainsonine (hybrid type), or 1-deoxymannojirimycin (high-mannose type). Deglycosylated glycoproteins (Asn-GlcNAc) were obtained by endoglucosaminidase H treatment of high-mannose-type glycoproteins. Ten minutes after intravenous injection 3% of complex type, 26% of hybrid type, 84% of high-mannose type. 64% of unglycosylated and 80% of deglycosylated alpha 1-acid glycoprotein disappeared from the plasma. The respective values for alpha 2-macroglobulin were 26%, 42%, 59% and 67%. When the clearance of total hepatic secretory proteins was examined, major differences between glycosylated and unglycosylated (glyco)proteins were found, particularly in the case of low-molecular-mass polypeptides. Whereas complex-type alpha 1-acid glycoprotein and alpha 2-macroglobulin showed no accumulation in various organs, hybrid-type alpha 1-acid glycoprotein and alpha 2-macroglobulin were present in spleen and liver. High-mannose-type alpha 1-acid glycoprotein and alpha 2-macroglobulin also accumulated mainly in spleen and liver. Spleen had the highest specific activity; liver, due to its larger organ mass, represented the major organ for the uptake of high-mannose-type glycoproteins. Competition experiments with mannan and GlcNAc-bovine-serum-albumin showed a mannose/GlcNAc receptor-mediated removal. Whereas unglycosylated alpha 1-acid glycoprotein was taken up by the kidney, unglycosylated alpha 2-macroglobulin was found in the spleen. Deglycosylated glycoproteins (Asn-GlcNAc) were removed from the plasma via two different mechanisms: firstly, clearance by the kidney similar to the unglycosylated glycoproteins; secondly, clearance by a mannose/GlcNAc receptor-mediated uptake mainly into the spleen. We conclude that N-linked oligosaccharide side chains are important for the plasma survival of hepatic secretory glycoproteins and that unphysiologically glycosylated forms are cleared by different mechanisms.
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PMID:Involvement of various organs in the initial plasma clearance of differently glycosylated rat liver secretory proteins. 245 61

The parameters of the reaction between a rat alveolar macrophage lectin (Mr = 180,000) and its ligands have been examined. The reaction is dependent on Ca2+ over the optimal pH range for binding. The apparent dissociation constant for fucosyl bovine serum albumin, the standard ligand used in these studies, is 1.4 X 10(-10) M. The ligand binding specificity was determined by measurement of the inhibition of binding of fucosyl bovine serum albumin by various glycoproteins and saccharides. D-Mannose, L-fucose, and N-acetyl-D-glucosamine were the most effective inhibitors, and D-galactose was much poorer. The equatorial hydroxyl groups on the C-3 and C-4 of the mannose ring are important in the lectin-ligand interaction, and the axial hydroxyl group on the C-2 contributes to a lesser extent. Immunocytological studies revealed that the lectin isolated from alveolar macrophages is widely distributed in other rat tissues. Hepatocytes are devoid of the lectin, but hepatic Kupffer cells and endothelial cells contain significant amounts. This was confirmed by isolation of the lectin from liver. Spleen and skeletal muscle also contain lectin, but much smaller amounts were found in brain, kidney, and heart muscle.
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PMID:The ligand binding specificity and tissue localization of a rat alveolar macrophage lectin. 353 11

A mitogenic substance, which stimulates murine and human B lymphocytes, has been isolated from the seeds of Ulex europeus. The m.w. of this mitogen was estimated to be approximately 100,000 by sodium dodecyl sulfate disc gel electrophoresis. Under physiologic conditions Ulex mitogen was in the form of a polymer. The isolated mitogen was found to contain 80% carbohydrate, in which glucose, galactose, and rhamnose were the predominant sugars. The carbohydrate portion of the mitogen could be responsible for the mitogenic activity, since the activity was destroyed by periodate treatment but not by protease digestion. It is unlikely that the mitogenic activity is due to the contamination by lipopolysaccharide (LPS), because Ulex mitogen strongly activated spleen cells from C3H/HeJ mice and did not contain a detectable amount of fatty acid. Spleen cells from nude mice, T-depleted spleen cells from conventional mice, or T-depleted spleen cells from conventional mice, or T-depleted lymphocytes from human peripheral blood responded as strongly as lymphocytes (T + B) from normal origin as measured by 3H-thymidine incorporation. It seems that the mitogenic effect is primarily on B cells. Ulex mitogen also induced the increase of immunoglobulin synthesis in murine and human B cells.
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PMID:Isolation and characterization of a mitogenic substance for murine and human B lymphocytes from Ulex europeus seeds. 626 9

The rapid plasma clearance of human placental beta-hexosaminidase in the cat is due mainly to a receptor-mediated mechanism recognizing terminal N-acetyl glucosaminyl and mannosyl residues on glycoproteins. Using a sensitive single radial immunodiffusion assay, specific for human beta-hexosaminidase, we have shown that, in normal cats, the liver is responsible for most of the clearance of human beta-hexosaminidase. Two hours after injection of approximately 6 X 10(6) U beta-hexosaminidase/kg bw, 70-90% of the enzyme was recovered in the liver. Spleen, kidney, lung, bone, bone, pancreas, adrenals, testes and ovaries, cardiac and skeletal muscle, lymph nodes, and placenta, however, also participated in the clearance, although specific uptake in most organs was < 5% of that of liver. Exogenous beta-hexosaminidase was also present in bile, indicating that the hepatocytes are involved in clearance. Injection of terminal mannose-rich S. cerevisiae mannans (50-150 mg/kg bw), prolonged the plasma half-life of the enzyme (t 1/2 up to 290 min). In these animals, beta-hexosaminidase uptake by liver was reduced to < 10% of controls but uptake by other organs was not proportionally or uniformly reduced, suggesting the existence of different uptake mechanisms in different tissues. Permeability of the blood-brain barrier was induced by exposing cats to 100% O2 at 2.5 ATA for 90 min. Injection of 6 X 10(6) U beta-hexosaminidase/kg bw during or immediately after exposure resulted in apparent uptake of enzyme by nervous tissue, qualitatively detectable by immunologic methods, but below the limits of sensitivity of the radial immunoassay(ie < 150 U/gr). When enzyme uptake by liver was inhibited by injection of ovomucoid or mannans, however, the hyperbaric oxygen-induced apparent uptake of beta-hexosaminidase by brain, cerebellum, and spinal cord was 200-500 U/gr of blood-free tissue, suggesting that the transport mechanism involved (presumably at the level of the nervous system vascular endothelium) is different from the carbohydrate-dependent hepatic uptake. The mechanism by which hyperbaric oxygenation induces permeability of the blood-brain barrier is not clear. The combination of this procedure (routinely used in human therapy) with specific inhibition of hepatic uptake, however, appears to be a promising approach for lysosomal enzyme targeting to the central nervous system.
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PMID:Towards enzyme replacement in GM2 gangliosidosis: organ disposition and induced central nervous system uptake of human beta-hexosaminidase in the cat. 677 24

In BALB/c mice repeatedly infested with nymphal Ixodes ricinus ticks, lymphocytes from axillary and brachial lymph nodes which drain the tick attachment site produced significant levels of IL-2, TNF-alpha and GM-CSF when stimulated in vitro with Con A or anti-CD3 antibodies. Cytokine production by cells from lymph nodes of the opposite flank was equivalent to that of cells from uninfested mice. Nine days after the first infestation and IL-2, GM-CSF were produced primarily by the CD4+ T cells, while some other cell types contributed also to the TNF-alpha production. In mice repeatedly infested, a gradual increase of lymph node cell production of IL-2 was observed. The IL-2 levels regularly increased from the first to the third infestation compared to TNF-alpha levels which gradually decreased. The in vitro production of GM-CSF was not affected by successive infestations. Spleen lymphocytes from naive mice produced higher levels of IL-2 than lymphocytes from axillary and brachial lymph nodes. Both tick salivary gland extracts and D-mannose inhibited IL-2 production by these lymphocytes.
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PMID:Cytokine production by lymph node cells from mice infested with Ixodes ricinus ticks and the effect of tick salivary gland extracts on IL-2 production. 884 33

The purpose of this study was to assess the antifungal activity of a new oral amphotericin B (AmpB) lipid-based formulation following administration to rats infected with Aspergillus fumigatus. Aspergillus fumigatus inoculum (2.1-2.5 x 10(7) colony forming units [CFU]) were injected via the jugular vein; 48h later male albino Sprague-Dawley rats (350-400 g) were administered either a single oral dose of AmpB incorporated into Peceol (50 mg AmpB/kg), physiologic saline (nontreated controls) or Peceol alone (vehicle control) once daily for 4 days. To assess antifungal activity Brain, Lung, Heart, Liver, Spleen and Kidney sections were homogenized with normal saline (1 mL/g of tissue) and a 0.1-mL aliquot was spread plated onto a Sabourand dextrose agar plate. The plates were incubated for 48 hr at 37 degrees C, at which time the number of fungal CFU were determined and corrected for tissue weight. In addition, plasma galactomannan antigen concentrations were determined. Data was reported as mean +/- standard error of the mean. The AmpB-Peceol oral formulation significantly decreased total fungal CFU concentrations recovered in all the organs added together, brain CFU concentrations, spleen CFU concentrations and plasma galactomannan antigen concentrations compared to baseline. No significant differences in lung, heart, liver and kidney CFU concentrations between treatment and control groups were observed. Peceol vehicle control did not exhibit any antifungal activity. These findings suggest that a new oral lipid-based formulation of AmpB incorporated into Peceol can significantly decrease brain and spleen CFU concentrations and plasma galactomannan antigen concentrations compared to non-treated controls.
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PMID:Assessing the antifungal activity of a new oral lipid-based amphotericin B formulation following administration to rats infected with Aspergillus fumigatus. 1765 18

Gaucher disease is caused by a deficiency of glucocerebrosidase. It is the first lysosomal storage disorder for which effective enzyme-supplementation therapy has become available. The enzyme, alglucerase, is glucocerebrosidase derived from human placental tissue; its oligosaccharide chain has been modified to expose terminal mannose residues, facilitating uptake in macrophages. Many patients have been shown to benefit from treatment with the enzyme. Spleen and liver volumes decrease and cytopenia improves. Over a longer period of time, bone involvement can also be diminished, although severe pre-existing bone abnormalities do not change. The safety profile of alglucerase seems excellent, with only few adverse events and approximately 12% of patients developing antibodies. Because long term safety is unknown and the enzyme is very expensive, studies have focused on the determination of the optimum individual dosage. Different dosages have shown to be effective, but so far the identification of patients who need a high or a low dosage is unclear. Other issues that deserve attention are the selection criteria for the initiation of treatment and the place of prophylactic treatment. Diversity in the course of the disease, which in many cases cannot be predicted by genotyping, hampers the establishment of strict rules. Multicentre studies, in which comparison of data is made possible by the use of standardised measurements of disease manifestations, may be needed to solve these issues.
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PMID:Alglucerase: practical guidance on appropriate dosage and administration in patients with Gaucher disease. 1802 May 53


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