Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We prospectively studied the effect of albendazole on microsomal reserve and on first-pass activation to albendazole sulfoxide in patients with hydatid disease. An aminopyrine breath test was performed in 12 patients while they were receiving albendazole treatment and while they were not. Excretion of 14CO2 in breath averaged 0.70%.kg.mmol-1 +/- 0.20%.kg.mmol-1 without treatment and 0.54%.kg.mmol-1 +/- 0.14%.kg.mmol-1 with treatment (p less than 0.005). Plasma levels of albendazole sulfoxide were measured 4 hours after the morning dose during the first and second half of the 4-week treatment cycles. In nine of the 12 patients albendazole sulfoxide levels decreased during the second half of the cycle by an average of 0.84 +/- 0.76 mumol/L (p less than 0.02). Transaminase levels increased in 10 of the 12 patients during long-term albendazole treatment, and major side effects, including hepatotoxicity, neutropenia, and alopecia, were observed in three patients. We conclude that albendazole partially inhibits microsomal enzyme function but induces its own metabolism. Hepatotoxicity and other possible severe side effects necessitate close therapeutic monitoring of patients who are given albendazole.
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PMID:Albendazole treatment of echinococcosis in humans: effects on microsomal metabolism and drug tolerance. 231 36

In type 1 glycogen storage diseases, glucose-6-phosphatase may be present but associated with impaired transport of glucose-6-phosphate (type 1b) or inorganic phosphate (type 1c) through microsomal membranes. The type 1c is very rare (2 published cases). The more frequent type 1b presents all the clinical manifestations of type 1a and specific signs: recurrent stomatitis, frequent infections, chronic inflammatory bowel disease secondary to neutropenia and neutrophil dysfunction. Glucose-6-phosphatase activity is low when measured on fresh liver tissue, but is restored after detergent treatment. A good metabolic control does not influence neutropenia and its consequences.
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PMID:[Glycogenoses type 1b and 1c]. 306 19

Polymorphonuclear leukocyte (PMN) function was investigated in two patients with glycogen storage disease type IB and neutropenia. Glycogen storage disease type IB was documented by liver biopsy and a normal amount of latent glucose-6-phosphatase activity. Patient A had stomatitis, skin infections, and septicemia; patient B had respiratory infections, periodontitis, and oral candidiasis. Absolute neutrophil counts ranged from 114 to 2580/mm3. Diminished and delayed migration of PMN into a skin "window" occurred in B. Random and directed PMN migration under agarose toward f-Met-Leu-Phe, pepstatin A, and zymosan-activated serum were severely diminished in both patients. At 10(-7) M f-Met-Leu-Phe, mean random and directed migration were 52 and 23% (A, n = 3) and 48 and 13% (B, n = 4) of controls. These results were independent of incubation time and chemoattractant concentration. Patients' PMN had diminished quantitative nitroblue tetrazolium reduction compared to controls. B had a significant defect in PMN bactericidal activity with Escherichia coli with less than 0.2 log killing at 2 h. These results further characterize the defect in PMN migration reported by Beaudet et al. (J Pediatr 97:906, 1980). The finding of other abnormalities of PMN function suggests a metabolic defect in the neutrophil which may be related to the microsomal membrane defect in hepatocytes in glycogen storage disease type IB.
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PMID:Impaired chemotaxis and neutrophil (polymorphonuclear leukocyte) function in glycogenosis type IB. 345 31

While classifications into generations according to antimicrobial activity has helped clinicians incorporate the increasing number of cephalosporins into their pharmacological repertoire, adverse effects among the different agents fail to follow similar categories. In general, cephalosporins are fairly well tolerated antibiotics, and toxicity has been limited to specific agents. Subtle differences in chemical structure and pharmacokinetics can influence the potential for adverse effects. The route of administration may result in minor adverse reactions, including thrombophlebitis and pain. The most common adverse effects of cephalosporins are allergic reactions, occurring in 0.9 to 3.2% of patients. Cephalosporins have very rarely been associated with haematological toxicity (less than 1% of patients), but specific agents have been associated with neutropenia, hypoprothrombinaemia, haemolytic anaemia, and problems with platelet production and function. Other reactions include localised gastrointestinal disturbances, hepatotoxicity (e.g. biliary sludging), nephrotoxicity and mild central nervous system effects. The cephalosporins are generally well tolerated in the paediatric population. Very few interactions have been observed between cephalosporins and other drugs, largely because cephalosporins do not affect the microsomal P450 hepatic enzyme system. While cephalosporins are considered to be relatively 'safe' drugs, the introduction of newer members warrants continued careful observation for reporting of adverse drug reactions.
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PMID:Adverse effects of newer cephalosporins. An update. 839 90

Glycogen-storage disease type 1 (GSD-1), also known as "von Gierke disease," is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase) activity. There are four distinct subgroups of this autosomal recessive disorder: 1a, 1b, 1c, and 1d. All share the same clinical manifestations, which are caused by abnormalities in the metabolism of glucose-6-phosphate (G6P). However, only GSD-1b patients suffer infectious complications, which are due to both the heritable neutropenia and the functional deficiencies of neutrophils and monocytes. Whereas G6Pase deficiency in GSD-1a patients arises from mutations in the G6Pase gene, this gene is normal in GSD-1b patients, indicating a separate locus for the disorder in the 1b subgroup. We now report the linkage of the GSD-1b locus to genetic markers spanning a 3-cM region on chromosome 11q23. Eventual molecular characterization of this disease will provide new insights into the genetic bases of G6P metabolism and neutrophil-monocyte dysfunction.
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PMID:The gene for glycogen-storage disease type 1b maps to chromosome 11q23. 946 34

The microsomal glucose-6-phosphatase (G6Pase) complex regulates the final step in glucose production from glycogenolysis and gluconeogenesis. Glycogen storage disease type 1c (GSD-1c) results from deficient activity of the phosphate/ pyrophosphate transporter of this complex and is associated with neutropenia as well as hepatomegaly and hypoglycaemia. Using three affected subjects from a single highly consanguineous family, we have used homozygosity mapping to localise the gene responsible for GSD-1c to a 10.2 cM region on 11q23.3-24.2. The maximum lod score was 3.12. GSD-1c is therefore distinct from GSD-1a, which has been shown previously to be caused by mutations in the G6Pase gene on chromosome 17.
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PMID:Localisation of the gene for glycogen storage disease type 1c by homozygosity mapping to 11q. 959 17

Glycogen storage disease type 1 (GSD-1) is a group of genetic disorders caused by a deficiency in the activity of the enzyme glucose-6-phosphatase. (G6Pase). GSD-1a and GSD-1b, the two major subgroups, have been confirmed at the molecular genetic level. The gene responsible for GSD-1b maps to human chromosome 11q23 and a candidate human GSD-1b cDNA that encodes a microsomal transmembrane protein has been identified. In this study, we show that this cDNA maps to chromosome 11q23; thus it is a strong candidate for GSD-1b. Furthermore, we isolated and characterized candidate murine and rat GSD-1b cDNAs. Both encode transmembrane proteins sharing 93-95% sequence homology to the human GSD-1b protein. The expression profiles of murine GSD-1b and G6Pase differ both in the liver and in the kidney; the GSD-1b transcript appears before the G6Pase mRNA during development. In addition to G6Pase deficiency, GSD-1b patients suffer neutropenia, neutrophil dysfunction, and recurrent bacterial infections. Interestingly, although the G6Pase mRNA is expressed primarily in the liver, kidney, and intestine, the GSD-1b mRNA is expressed in numerous tissues, including human neutrophils/monocytes.
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PMID:Cloning and characterization of cDNAs encoding a candidate glycogen storage disease type 1b protein in rodents. 982 26

Glycogen storage disease type 1b (GSD-1b) is proposed to be caused by a deficiency in microsomal glucose 6-phosphate (G6P) transport, causing a loss of glucose-6-phosphatase activity and glucose homeostasis. However, for decades, this disorder has defied molecular characterization. In this study, we characterize the structural organization of the G6P transporter gene and identify mutations in the gene that segregate with the GSD-1b disorder. We report the functional characterization of the recombinant G6P transporter and demonstrate that mutations uncovered in GSD-1b patients disrupt G6P transport. Our results, for the first time, define a molecular basis for functional deficiency in GSD-1b and raise the possibility that the defective G6P transporter contributes to neutropenia and neutrophil/monocyte dysfunctions characteristic of GSD-1b patients.
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PMID:Inactivation of the glucose 6-phosphate transporter causes glycogen storage disease type 1b. 1002 67

The purpose of this work was to test the hypothesis that mutations in the putative glucose 6-phosphate translocase gene would account for most of the cases of GSD I that are not explained by mutations in the phosphohydrolase gene, ie that are not type Ia. Twenty-three additional families diagnosed as having GSD I non-a (GSDIb, Ic or Id) have now been analysed. The 9exons of the gene were amplified by PCR and mutations searched both by SSCP and heteroduplex analysis. Except for one family in which only one mutation was found, all patients had two allelic mutations in the gene encoding the putative glucose 6-phosphate translocase. Sixteen of the mutations are new and they are all predicted to lead to non-functional proteins. All investigated patients had some degree of neutropenia or neutrophil dysfunction and the clinical phenotype of the four new patients who had been diagnosed as GSD Ic and the one diagnosed as GSD Id was no different from the GSD Ib patients. Since these patients, and the four type Ic patients from two families previously studied, shared several mutations with GSD Ib patients, we conclude that their basic defect is in the putative glucose 6-phosphate translocase and that they should be reclassified as GSD Ib. Isolated defects in microsomal Pi transporter or in microsomal glucose transporter must be very rare or have phenotypes that are not recognised as GSD I, so that in practice there are only two subtypes of GSD I (GSD Ia and GSD Ib).
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PMID:The putative glucose 6-phosphate translocase gene is mutated in essentially all cases of glycogen storage disease type I non-a. 1048 62

Type Ib glycogenosis is a rare glycogen storage disorder resulting from a defect in the enzyme, glucose-6-phosphatase microsomal translocase. We report a case of Type Ib glycogenosis in an 18 month-old male child who presented with a history of hypoglycemic seizures and recurrent infections and had a massive hepatomegaly, recurrent hypoglycemia, hyperuricemia, hypertriglyceridemia, neutropenia and fasting lactacidemia which decreased sharply on glucose administration.
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PMID:Type Ib glycogenosis. 1077 88


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