Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocarboxylic acid derivaties of vitamin B12 were covalently coupled to 1,6-hexanediamine-substituted Sepharose by using a water-soluble carbodiimide resulting in 1.32 micronmoles of B12 coupled per ml of Sepharose. After a source of crude hog intrinsic factor (IF) was passed over the column, a selective linear gradient of guanidine HC1 (0 to 4.0 M) was used to remove IF and 4.0 to 7.5 M to elute NIF (a vitamin B12-binding glycoprotein not active in promoting vitamin B12 absorption). Anti-IF antibodies blocked 99% of the B12 binding by the isolated IF and only 1% of the B12 binding by NIF. Passage over a hydroxyapatite column resulted in IF 99% pure with a specific activity of 29.8 microng of B12 binding per mg of protein. IF so isolated exhibited one homogeneous band on polyacrylamide gel electrophoresis and corrected B12 malabsorption in a patient with pernicious anemia.
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PMID:Purification of hog gastric intrinsic factor by a simple two-step procedure based on affinity chromatography and a selective guanidine hydrochloride gradient. 87 Mar 79

The coeliac disease (CD) or gluten-sensitive enteropathy (GSE) is a permanent intolerance to wheat gliadin and to correlated proteins inducing malabsorption and typical damages of the jejunal mucosa (total or subtotal villous atrophy = SVA) in genetically-predisposed individuals ("DQW2"). A large amount of research has been devoted to CD pathogenesis: the most recent studies, thanks to sophisticated and experimental methods, support the pathogenetic immunological theory and the one of direct cytotoxicity. The correct diagnostic procedure for CD, established in 1970 by the European Society for Pediatric Gastroenterology and Nutrition (ESPGAN), suggested three small bowel mucosal biopsies. In the last years, because of the difficulties of such a practice, the necessity of non-invasive diagnostic approaches has developed; such approaches have been verified in absorption tests (one-hour blood xylose, intestinal permeability methods) and in immunogenetic tests (antibodies antigliadin, anti-reticulin, anti-endomysium, anti 90 KD glycoprotein, anti-human jejunum, HLA I/II antigens). The specific MHC antigens establish CD's incidence in several population and in particular situations, as in first-degree relatives and in diseases associated with CD (dermatitis herpetiformis (DH), insulin dependent diabetes mellitus (IDDM) and other auto-immune syndromes). The specific serum antibodies singly used as first level screening if estimated in combination with absorption tests, reach the highest levels of specificity and sensibility in CD diagnosis. It's anyway fundamental the comparison with at least a typical CD histological feature, caused by a challenge with a sufficient gluten to be carried in dubious cases and in non high auxological risk age (ESPGAN 1989). Adolescence is a period of frequent non compliance with a gluten-free diet and of particular psychological and physical problems: the apparent "gluten insensitivity", typical of teen-agers and adults, recalls the definitions of silent CD and latent CD (iceberg like). In the first case the jejunal mucosa is abnormal and the symptomatology isn't evident. In latent CD, genetically restricted, the mucosa is normal but there are minimal markers of inappropriate immunity to gliadin (at intestinal humoral immunity level) and a possible worsening of histological lesions to the third stage under environmental stimuli. This represents a two-stage model CD. That's why CD is still under-evaluated despite recent statistics reporting an increasing incidence (late and atypical forms). Prevalence rates between 1:300 and 1:4,000 and more are quoted in literature. The necessity of a strict gluten-free diet is confirmed by the evident frequency of lymphoma and by the increased risk of malignancy in untreated CD.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Celiac disease and its diagnostic evolution. Comparisons and experiences in a hospital pediatric department (1975-1992). I]. 152 93

The significance of the human immunodeficiency virus (HIV) in the small intestinal lamina propria in patients with the acquired immune deficiency syndrome or conditions related to that syndrome who have chronic diarrhea and malabsorption is unclear. To investigate this issue, upper endoscopy (after a 12- to 16-hour fast) with duodenal biopsy and aspirate was performed in 20 HIV-infected seropositive homosexual men referred for diarrhea of more than 8 weeks duration (Group 2) and in 9 HIV-infected homosexual men referred for dysphagia or dyspepsia with no symptoms of malabsorption (Group 1). All biopsy specimens were examined by light microscopy and immunochemical staining with monoclonal antibody against HIV glycoprotein gp41. Electron microscopy was performed in 18 patients in Group 2 and in all patients in Group 1. Immunogold electron microscopy was used as a confirmatory test for identified HIV particles. In addition, D-xylose absorption was measured in all patients after a 25-g dose of D-xylose with measurement of serum D-xylose concentration 1 hour after the dose and measurement of 5-hour urinary D-xylose excretion. Mean serum D-xylose was 35.4 +/- 4.5 mg/dL in Group 1 and 15.8 +/- 2.3 mg/dL in Group 2 (P less than 0.001), whereas mean urine D-xylose was 5.5 +/- 0.6 g in Group 1 and 2.0 +/- 0.4 g in Group 2 (P less than 0.001). Immunoperoxidase for gp41 was positive in 5 (56%) patients in Group 1 and in 12 (60%) patients in Group 2. Lamina propria HIV viral particles were identified by electron microscopy in both patient groups. Viral particles were seen within and adjacent to the cytoplasm of mononuclear cells and were not present in enterocytes or neuroendocrine cells. There were no significant differences in serum or urine D-xylose tests between patients with and without lamina propria HIV. In addition, lipid accumulation in intercellular spaces near the basolateral membrane of adjacent enterocytes was seen in 33% of patients with chronic diarrhea. These findings suggest that lamina propria HIV is not a direct cause of enteropathy in HIV-infected patients and that lymphatic obstruction may be one pathophysiologic mechanism producing this malabsorptive state.
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PMID:Histopathologic findings of duodenal biopsy specimens in HIV-infected patients with and without diarrhea and malabsorption. 141 28

A patient aged 45 suffering from Whipple's disease is described. The disease has been diagnosed on the basis of morphologic examination of a biopsy specimen of the small intestine mesenteric lymph node. The patient had suffered from the disease for 14 years; during the last 6 months he developed symptoms of the malabsorption syndrome with diarrhea and steatorrhea. The lymph nodes contained numerous macrophages with PAS-positive glycoprotein granules in the cytoplasm, small cavities filled with lipids; electron microscopy has revealed bacillus-like bodies in the macrophages and outside the cells. After the disease has been diagnosed, the patient has been administered a course of tetracycline therapy, that resulted in an improvement of his status.
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PMID:[The morphology of mesenteric lymph nodes in Whipple's disease]. 246 43

The gastric pentagastrin-stimulated secretions of acid (peak acid output) and of unsaturated intrinsic factor in eight cystic fibrosis patients (1.4 +/- 0.5 mEq/kg/h and 0.27 +/- 0.12 nmol/kg/h, respectively) were significantly enhanced (p less than 0.05) when compared with six normal controls (0.27 +/- 0.16 mEq/kg/h and 0.10 +/- 0.02 nmol/kg/h, respectively). Despite the gastric hypersecretion of intrinsic factor, no significant physicochemical modification of this glycoprotein was observed in cystic fibrosis when using gel filtration and isoelectrofocusing. Haptocorrin (a cobalamin glycoproteic binder that does not promote the assimilation of cobalamin) also increased in gastric juice after stimulation. Since the sequestration of cobalamin to haptocorrin is pH dependent, the gastric acid hypersecretion observed in cystic fibrosis may explain that the malabsorption of crystalline cobalamin is much more frequent in cystic fibrosis than in chronic pancreatitis.
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PMID:Gastric intrinsic factor hypersecretion stimulated by pentagastrin in cystic fibrosis. 368 75

Zinc deficiency has been associated with impared carbohydrate absorption in patients with intestinal disease; however, it is not known whether the carbohydrate malabsorption is caused by the zinc abnormality. Because zinc is needed for protein synthesis, we investigated the effect of zinc deficiency on the total and specific activities of the intestinal glycoprotein disaccharidases. We found that zinc deficiency impairs total body growth and causes marked reductions in intestinal mucosal protein content and disaccharidase activity. However, the protein content and disaccharidase activities were reduced to a similar degree, and both were proportional to the final total body weight. We also found zinc deficiency to have no effect on intestinal villus height or crypt depth. We conclude that zinc deficiency inhibits somatic growth but does not disproportionately affect intestinal mucosal protein content, disaccharidase activity, or intestinal architecture.
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PMID:Does zinc deficiency affect intestinal protein content or disaccharidase activity? 393 98

The physiological absorption of vitamin B12 is a complex process which requires the interaction of several macromolecules. Mediated by the glycoprotein, intrinsic factor (IF), this process requires formation of a primary complex between vitamin B12 and IF (IF-B12), the recognition and binding of this complex to specific ileal receptors and the transport of vitamin B12 across the ileal cell. As a measure of this overall process, the vitamin B12 absorption test has helped to identify abnormal vitamin B12 absorption in patients with exocrine pancreatic insufficiency and familial vitamin B12 malabsorption (Immerslung-Grasbeck syndrome). Progress into understanding the role of proteolytic enzymes in promoting vitamin B12 absorption as well as the molecular events of vitamin B12 transport across the ileal cell has been brought about by recent investigation based upon this determination.
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PMID:Intrinsic factor mediated cobalamin absorption. 700 31

Content of IgA, IgG, IgM, C3 and C4 components of complement, properdin factor B, acid glycoprotein, alpha 1-antitrypsin, transferrin and ceruloplasmin were studied using immunochemical procedures in blood serum, gastric and duodenal contents of healthy persons and of patients after stomach resection. In patients with symptoms of malabsorption concentration of IgA and IgG was drastically increased in gastric and duodenal contents by 51% and 188%, respectively, and by 53% and 371%, respectively. Local activation of the complement system was also observed, which involved an increase of C3 component in stomach and small intestine by 122% and 31%, respectively. As a result of postoperative anastomositis content of albumin and the properdin factor B was distinctly increased in the duodenum. The data obtained suggest that studies of various functional proteins in gastric and duodenal contents are recommended for evaluation of a disease genesis as well as for diagnosis of acute local inflammation.
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PMID:[The local humoral immune system in patients with malabsorption syndrome]. 816 Apr 29

The Na+/glucose cotransporter gene SGLT1 encodes the primary carrier protein responsible for the uptake of the dietary sugars glucose and galactose from the intestinal lumen. SGLT1 transport activity is currently exploited in oral rehydration therapy. The 75-kDa glycoprotein is localized in the brush border of the intestinal epithelium and is predicted to comprise 12 membrane spans. In two patients with the autosomal recessive disease glucose/galactose malabsorption, the underlying cause was found to be a missense mutation in SGLT1, and the Asp28-->Asn change was demonstrated in vitro to eliminate SGLT1 transport activity. The SGLT1 gene was previously shown to reside on the distal q arm of chromosome 22 (11.2-->qter). We have used a cosmid probe for fluorescence in situ hybridization, which refines the localization to 22q13.1, and provide an example of the utility of the SGLT1 probe as a diagnostic for genetic diseases associated with translocations of chromosome 22.
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PMID:Assignment of the human Na+/glucose cotransporter gene SGLT1 to chromosome 22q13.1. 824 93

Since its introduction in 1987, zidovudine monotherapy has been the treatment of choice for patients with HIV infection. Unfortunately it has been established that the beneficial effects of zidovudine are not sustained due to the development of resistant viral strains. This has led to the strategy of combination therapy, and in 1995 treatment with zidovudine plus didanosine, or zidovudine plus zalcitabine, was demonstrated to be more effective than zidovudine monotherapy in preventing disease progression and reducing mortality in patients with HIV disease. Recent work demonstrates an even greater antiviral effect from triple therapy with 2 nucleosides, zidovudine plus zalcitabine with the addition of saquinavir, a new protease inhibitor drug. The HIV protease enzyme is responsible for the post-translational processing of gag and gag-pol polyprotein precursors, and its inhibition by drugs such as saquinavir, ritonavir, indinavir and VX-478 results in the production of non-infectious virions. As resistance may also develop to the protease inhibitors they may be used in combination, and future strategies may well include quadruple therapy with 2 nucleoside analogues plus 2 protease inhibitors. Administration of protease inhibitors alone or in combination with other drugs does raise a number of important pharmacokinetic issues for patients with HIV disease. Some protease inhibitors (e.g. saquinavir) have kinetic profiles characterised by reduced absorption and a high first pass effect, resulting in poor bioavailability which may be improved by administrating with food. Physiological factors including achlorhydria, malabsorption and hepatic dysfunction may influence the bioavailability of protease inhibitors in HIV disease. Protease inhibitors are very highly bound to plasma proteins (> 98%), predominantly to alpha 1-acid glycoprotein. This may influence their antiviral activity in vitro and may also predispose to plasma protein displacement interactions. Such interactions are usually only of clinical relevance if the metabolism of the displaced drug is also inhibited. This is precisely the situation likely to pertain to the protease inhibitors, as ritonavir may displace other protease inhibitor drugs, such as saquinavir, from plasma proteins and inhibit their metabolism. Protease inhibitors are extensively metabolised by the cytochrome P450 (CYP) enzymes present in the liver and small intestine. In vitro studies suggest that the most influential CYP isoenzyme involved in the metabolism of the protease inhibitors is CYP3A, with the isoforms CYP2C9 and CYP2D6 also contributing. Ritonavir has an elimination half-life (t1/2 beta) of 3 hours, indinavir 2 hours and saquinavir between 7 and 12 hours. Renal elimination is not significant, with less than 5% of ritonavir and saquinavir excreted in the unchanged form. As patients with HIV disease are likely to be taking multiple prolonged drug regimens this may lead to drug interactions as a result of enzyme induction or inhibition. Recognised enzyme inducers of CYP3A, which are likely to be prescribed for patients with HIV disease, include rifampicin (rifampin) [treatment of pulmonary tuberculosis], rifabutin (treatment and prophylaxis of Mycobacterium avium complex), phenobarbital (phenobarbitone), phenytoin and carbamazepine (treatment of seizures secondary to cerebral toxoplasmosis or cerebral lymphoma). These drugs may reduce the plasma concentrations of the protease inhibitors and reduce their antiviral efficacy. If coadministered drugs are substrates for a common CYP enzyme, the elimination of one or both drugs may be impaired. Drugs which are metabolised by CYP3A and are likely to be used in the treatment of patients with HIV disease include the azole antifungals, macrolide antibiotics and dapsone; therefore, protease inhibitors may interact with these drugs. (ABSTRACT TRUNCATED)
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PMID:Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations. 908 59


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