PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “DEFICIENCY DISEASES”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMedDate not supplied

Enzyme replacement therapy in the mouse model of Pompe disease.

Deficiency of acid alpha-glucosidase (GAA) results in widespread cellular deposition of lysosomal glycogen manifesting as myopathy and cardiomyopathy. When GAA-/- mice were treated with rhGAA (20 mg/kg/week for up to 5 months), skeletal muscle cells took up little enzyme compared to liver and heart. Glycogen reduction was less than 50%, and some fibers showed little or no glycogen clearance. A dose of 100 mg/kg/week resulted in approximately 75% glycogen clearance in skeletal muscle. The enzyme reduced cardiac glycogen to undetectable levels at either dose. Skeletal muscle fibers with residual glycogen showed immunoreactivity for LAMP-1/LAMP-2, indicating that undigested glycogen remained in proliferating lysosomes. Glycogen clearance was more pronounced in type 1 fibers, and histochemical analysis suggested an increased mannose-6-phosphate receptor immunoreactivity in these fibers. Differential transport of enzyme into lysosomes may explain the strikingly uneven pattern of glycogen removal. Autophagic vacuoles, a feature of both the mouse model and the human disease, persisted despite glycogen clearance. In some groups a modest glycogen reduction was accompanied by improved muscle strength. These studies suggest that enzyme replacement therapy, although at much higher doses than in other lysosomal diseases, has the potential to reverse cardiac pathology and to reduce the glycogen level in skeletal muscle.

Animals↗
PubMed1995

[Acid lipase deficiency: Wolman disease and cholesteryl ester storage disease].

Wolman disease and cholesteryl ester storage disease (CESD) are caused by a deficiency of lysosomal acid lipase activity, resulting in massive accumulation of cholesteryl ester and triglycerides. Wolman disease occurs in infancy, with hepatosplenomegaly, steatorrhea and adrenal calcification. It is fatal before the age of 1 year. In CESD, hepatomegaly may be the only clinical abnormality, although lipid deposition is widespread. Lysosomal acid lipase hydrolyzes both triaclyglycerols and cholesteryl esters, and the enzyme plays an important role in the cellular processing of plasma lipoproteins, and contributes to homeostatic control of lipoprotein levels in blood and prevention of cellular lipid overloading. The gene encoding lysosomal acid lipase was cloned and characterized in 1994, and two mutations of acid lipase gene were found in a patient with Wolman disease, as a compound heterozygote. It is suggested that structural gene defects are also present in CESD cells. However, the reason (s) for the clinical difference between Wolman disease and CESD remain (s) to be studied.

Cholesterol Ester Storage Disease↗
PubMed1975

Metabolism of human erythrocytes. Studies in health and disease.

Deficiency states have been well established in nine enzymes of anaerobic glycolysis and suggested, but inadequantely confirmed, in others. In additon, hemolytic anemia has been defined in glucose-6-phosphate dehydrogenase deficiency, in certain enzymes glutathione metabolism of importance to the function of the oxidative hexsemonophosphate shunt, and in certain enzymes of nucleotide metabolism. In heterogeneous dyserythropoietic states with ineffective erythropoiesis, enzyme ratios are grossly distorted and differ greatly from those of either normal or reticullocyte-rich blood. Red blood cell (RBC) enzyme deficiencies show noticeable genetic polymorphism, most apparently recessively transmitted anemias actually resulting from inheritance of two different mutant, allelic genes. In addition to causing hemolytic syndromes in selected instances, deficiencies of enzymes more important to other tissues than to the RBC itself are detectable by assay of hemolystates.

Anemia, Hemolytic↗
PubMed2003

Urinary bile acid profile in children with inborn errors of bile acid metabolism and chronic cholestasis; screening technique using electrospray tandem mass-spectrometry (ES/MS/MS).

BACKGROUND: It is well known that urine becomes the major route for bile acid excretion in liver diseases and thus we examined bile acid profile in urine obtained from normal children and children having chronic liver diseases using electrospray tandem mass spectrometry (ES/MS/MS). MATERIAL/METHODS: Bile acid were extracted from 5 ml of urine obtained from five healthy children or from twenty patients with various liver diseases including patients with unknown chronic liver diseases, Zellweger syndrome, peroxisomal bifunctional protein deficiency disease, tyrosinema type 1, biliary atresia, and patients with progressive familial intrahepatic cholestasis (PFIC) of undetermined type. Identification and quantification of bile acids were achieved in 5 minutes using electrospray tandem mass spectrometry (ES/MS/MS). RESULTS: Urinary bile acid excretion increased in liver diseases an average of 100 times as compared to control values. There was a specific profile for different liver disease which confirms the pathology of the disease and could be used for its diagnosis. The results also show that the ions used for the diagnosis of oxo-steroid reductase deficiency disease were present in other chronic liver diseases suggesting that these atypical bile acids may not be a result of an inborn error of bile acid metabolism. CONCLUSIONS: The urinary bile acid profile obtained in this study by ES/MS/MS can be of use for the diagnosis of certain chronic liver diseases.

Bile Acids and Salts↗
PubMed1990

[Vitamin B12 deficiency: neurological disease with minimal or no anemia].

3 patients with vitamin B12 deficiency are described (men aged 64 and 67 and a women of 75). All presented with neurological disease; 2 had had severe weight loss. In 1 neither anemia nor macrocytosis was found, while in 2 there was only mild macrocytic anemia, so that the diagnosis was established quite late during the disease. These patients demonstrate that a high index of suspicion is required to diagnose vitamin B12 deficiency when there are only mild or no hematological abnormalities. This is especially important because of the direct relation between time elapsed before therapy and the irreversibility of neurological damage. Of note is the severe weight loss simulating malignant disease that can be the presenting symptom or appear during the course of the disease.

Aged↗
PubMed2004

[Hypothesis: Parkinson's disease, reward deficiency syndrome and addictive effects of levodopa].

Since Parkinson's disease (PD) patients could suffer from a reward deficiency syndrome, they are particularly prone to develop addictive behaviours. Dopamine is involved in reward processing and in addiction. Pulsatile administration of antiparkinsonian drugs may lead to the development of dyskinesias and addictive behaviours. However, this phenomenon occurs in very few cases. Indeed, both processes share molecular mechanisms although with some differences such as the topography of the changes (it predominates in motor regions in PD with dyskinesias and in limbic regions in addictions). Nevertheless, investigations conducted to know the physiopathology of levodopa-induced dyskinesias may lead to important cues for understanding the underlying mechanisms responsible for addiction. Thus, this may have important implications for the discovery of new therapeutic strategies.

Adult↗
PubMed1985

Decreased natural killer cell activity in patients with zinc deficiency with sickle cell disease.

Zinc deficiency is associated with depression of a number of immune responses. To assess the relationship of zinc and natural killer activity, we studied natural killer activity in adults with sickle cell disease and in two normal volunteers rendered zinc deficient by dietary restriction. Natural killer activity was significantly lower in patients with sickle cell disease and zinc deficiency (5.1 +/- 2.9 lytic units per 10(6) cells) than in controls (11.7 +/- 5.0 lytic units per 10(6) cells). In the two volunteers, natural killer activity declined during zinc restriction and returned to near initial levels with zinc repletion. These results suggest that zinc deficiency is associated with a lowering of natural killer activity.

Adult↗
PubMed1983

Iron deficiency in health and disease.

Iron deficiency is a common problem in otherwise healthy children and in children with systemic disease. We have reviewed the pathophysiology, laboratory diagnosis, and systemic effects of iron deficiency. We have emphasized that routine screening procedures do not efficiently predict those otherwise healthy children who will demonstrate a therapeutic response to iron. Furthermore, in patients with certain systemic diseases the diagnosis of iron deficiency is complicated by the inflammatory process and the response to a therapeutic trial of oral iron is often blunted. Since the potential adverse effects of iron deficiency may be extensive, a therapeutic trial of iron is indicated to establish the diagnosis of iron deficiency if the index of suspicion is high and laboratory results are equivocal.

Adolescent↗
PubMed1989

Lectin histochemistry of an ovine lysosomal storage disease with deficiencies of beta-galactosidase and alpha-neuraminidase.

Lectin histochemistry is a useful technique to identify and to localize in cells and tissues the terminal carbohydrate moieties of glycoproteins and glycolipids. The specific diagnosis of some glycoprotein storage diseases was accomplished using lectin staining patterns, and such methods of diagnosis have been attempted for some glycolipid storage diseases. This technique was applied to formalin-fixed paraffin-embedded and frozen neural, hepatic, and renal tissues of sheep with an inherited lysosomal storage disease with deficiencies of beta-galactosidase and alpha-neuraminidase. The cytoplasm of central nervous system neurons of affected sheep in paraffin-embedded sections stained with peanut agglutinin (PNA), Ricinus communis agglutinin-I (RCA-I), Dolichos biflorus agglutinin (DBA), and soybean agglutinin (SBA). The cytoplasm of neurons in frozen sections of these tissues stained with PNA, RCA-I, wheat germ agglutinin (WGA), and Ulex europaeus agglutinin-I (UEA-I). The cytoplasm of frozen and paraffin-embedded sections of liver and kidney of affected sheep stained with PNA, whereas paraffin-embedded sections also stained with RCA-I. These results suggest the stored material in this disease has terminal saccharide moieties consisting of beta-galactose, N-acetylneuraminic acid, and N-acetylgalactosamine. Paraffin processing altered lectin staining patterns. Although the staining pattern in this glycolipid storage disease was complex, lectin histochemistry may prove to be a useful technique for the characterization of storage products and for the diagnosis of lysosomal storage diseases.

Animals↗
PubMed2000

Mitochondrial basis for immune deficiency. Evidence from purine nucleoside phosphorylase-deficient mice.

We generated purine nucleoside phosphorylase (PNP)-deficient mice to gain insight into the mechanism of immune deficiency disease associated with PNP deficiency in humans. Similar to the human disease, PNP deficiency in mice causes an immunodeficiency that affects T lymphocytes more severely than B lymphocytes. PNP knockout mice exhibit impaired thymocyte differentiation, reduced mitogenic and allogeneic responses, and decreased numbers of maturing thymocytes and peripheral T cells. T lymphocytes of PNP-deficient mice exhibit increased apoptosis in vivo and higher sensitivity to gamma irradiation in vitro. We propose that the immune deficiency in PNP deficiency is a result of inhibition of mitochondrial DNA repair due to the accumulation of dGTP in the mitochondria. The end result is increased sensitivity of T cells to spontaneous mitochondrial DNA damage, leading to T cell depletion by apoptosis.

Animals↗
PubMed1988

Pathogenesis of NIDDM--a disease of deficient insulin secretion.

Type 2 diabetes is a familial disease and studies of both Caucasian and Japanese families have raised the possibility that a major susceptibility gene is involved. The majority of patients have both beta cell dysfunction and impaired insulin sensitivity but studies of relatives of Type 2 diabetic patients suggest that beta cell dysfunction is an early feature of the disease. Impaired insulin sensitivity, from acromegaly, Cushing's disease or steroid therapy, induces diabetes only in a small proportion of the population, and they may be those who have an inherited cell defect. We postulate that a single beta cell defect gene, on its own, may be insufficient to cause overt diabetes and would lead to life-long glucose intolerance unless associated with other defects such as impaired insulin sensitivity. The nature of such a postulated beta cell defect is uncertain. Whilst it has been reported to be specific to glucose, and not to non-glucose stimuli, this feature may be secondary to hyperglycaemia. The occurrence of islet amyloid in 70-90% of Type 2 diabetic patients, and rarely in the normal population, raises the possibility that amyloid deposition causing disruption of the islet is a factor which might affect beta cell function. Amyloid formation may be a primary abnormality or could be secondary to beta cell dysfunction induced by hyperglycaemia. A major susceptibility gene might predispose a proportion, perhaps 10-15%, of a Caucasian population towards diabetes. The subsequent development of diabetes in a particular patient is likely to depend on many factors including other genetic factors, a sedentary life style and obesity. In different populations different genetic influences may operate, including abnormalities of insulin receptor genes and glucose transporter genes, which may allow a beta cell abnormality to become expressed clinically.

Diabetes Mellitus, Type 2↗
PubMed2003

Alveolar macrophages from subjects with chronic obstructive pulmonary disease are deficient in their ability to phagocytose apoptotic airway epithelial cells.

Chronic obstructive pulmonary disease is a highly prevalent, complex disease, usually caused by cigarette smoke. It causes serious morbidity and mortality and costs the global community billions of dollars per year. While chronic inflammation, extracellular matrix destruction and increased airway epithelial cell apoptosis are reported in chronic obstructive pulmonary disease, the understanding of the basic pathogenesis of the disease is limited and there are no effective treatments. We hypothesized that the accumulation of apoptotic airway epithelial cells chronic obstructive pulmonary disease in could be due to defective phagocytic clearance by alveolar macrophages. There have been no previous studies of the phagocytic capacity of alveolar macrophages in chronic obstructive pulmonary disease using physiologically relevant apoptotic airway epithelial cells as phagocytic targets. We developed a phagocytosis assay whereby cultured 16HBE airway epithelial cells were induced to apoptosis with ultraviolet radiation and stained with mitotracker green. Alveolar macrophages from bronchoalveolar lavage from eight control and six chronic obstructive pulmonary disease subjects were analysed following 1.5 h incubation with apoptotic airway epithelial cells, then staining with macrophage marker anti CD33. CD33+/mitotracker green + events (i.e., alveolar macrophages which had phagocytosed apoptotic airway epithelial cells) were analysed using flow cytometry. Phagocytosis of polystyrene microbeads was investigated in parallel. A significantly reduced proportion of alveolar macrophages from chronic obstructive pulmonary disease subjects ingested apoptotic airway epithelial cells compared with controls (11.6 +/- 4.1% for chronic obstructive pulmonary disease versus 25.6 +/- 9.2% for control group). Importantly, the deficiency was not observed using polystyrene beads, suggesting that the failure to resolve epithelial damage in chronic obstructive pulmonary disease may result, at least partially, from specific defects in phagocytic ability of alveolar macrophages to ingest apoptotic airway epithelial cells.

Aged↗
PubMedDate not supplied

[Activity and appearance of isoenzyme spectrums of some lysosomal hydrolases in biopsy material of human chorion].

Activities and isozyme spectra of alpha-L-fucosidase and beta-D-hexosaminidase were similar both in biopsy material from fetal zone of placenta (chorion) and in chorion tissue obtained after abortion. Evaluation of the isozyme spectrum of these glycosidases in biopsy reeterial of chorion might be carried out for prenatal detection of fucosidosis (deficiency of alpha-L-fucosidase), Tay-Sachs disease (deficiency of hexosaminidase A) and of Sandhoff disease (deficiency of hexosaminidases A and B).

Abortion, Spontaneous↗
PubMed1994

Phytanic acid alpha-oxidase deficiency (Refsum disease) presenting in infancy.

This report describes a patient with high serum phytanic acid concentration due to phytanic acid alpha-oxidase deficiency (classical Refsum disease). He presented unusually early, hypotonia and developmental delay being apparent by 7 months. A generalized peroxisomal disorder (so-called 'infantile Refsum disease') was excluded by analyses of pristanic acid, very long-chain fatty acids, bile acids and plasmalogen synthesis. The early presentation raises the possibility of in utero exposure to phytanate.

Gas Chromatography-Mass Spectrometry↗
PubMed1992

Malnutrition in Crohn's disease: substrate deficiency or misuse?

Growth failure is frequently associated with Crohn's disease. However, it does not seem to be fully accounted for by overt endocrinological abnormalities or nutrient deficiencies. It may be related to an abnormal utilization of available substrates, particularly proteins, due to an imbalance in protein metabolism kinetics. Its primary mechanism may be an increase in protein breakdown rates over synthesis, specifically related to the associated inflammatory syndrome, and progressively leading to a protein debt. Reduction in food intake would only exaggerate this trend by further reducing the synthesis to breakdown ratio, whereas nutrient supplementation merely compensates for the deficit by promoting protein synthesis.

Child↗
PubMed2003

Plasma cytokine profiles in patients with celiac disease and selective IgA deficiency.

Celiac disease (CD) and selective IgA deficiency (IgAD) are frequently associated, and share the same genetic background. The aim of the present study was to evaluate both Type 1 and 2 plasma cytokine levels in CD and in CD-IgAD. IL-2, TNF-alpha, IL-10, IL-4 and IL-13 plasma levels were measured both at diagnosis and after a gluten-free diet (GFD) in 32 CD patients, in 27 CD-IgAD patients and in 30 healthy controls. IFN-gamma levels were significantly higher in CD and CD-IgAD than in controls, TNF-alpha displayed significantly higher levels in CD-IgAD when compared both with controls and with CD, and IL-2 was in CD-IgAD significantly increased respect to controls. Kinetics of the Type 1 cytokine plasma levels did not show a clear relationship with the GFD in both groups of CD patients, and particularly in those with IgAD. IL-4 and IL-13, both at diagnosis and after a GFD, were not significantly different in controls and in celiac patients (with and without IgAD). IL-10, whose production is stimulated by the TNF-alpha, had significantly higher plasma levels in CD-IgAD, but not in CD patients, with a significant decrease after a GFD. CD and especially CD-IgAD patients display persistently higher pro-inflammatory cytokine levels, suggesting a persistent state of activation of pro-phlogistic signals in CD, particularly when IgAD coexists. Serial measurement of serum IL-10 may be an adjunctive evaluating criterion in the follow-up of CD-IgAD patients.

Adolescent↗
PubMed1993

Mankind and plants: the need to conserve biodiversity.

Only green plants can convert the single carbon units of atmospheric carbon dioxide into the multi-carbon organic molecules on which all forms of life depend. Only green plants can provide the oxygen required by man and other aerobic organisms. In addition to his basic need for preformed organic molecules and oxygen, man also depends on plants to provide him, directly or indirectly, with an array of specific compounds such as vitamins and essential amino acids. Inadequate supplies of these may hinder growth and development or give rise to well defined deficiency diseases. At the present time information concerning the distribution and concentrations of such essential nutrients in plants is largely restricted to those plants that are already used as human foods. Nothing or virtually nothing is known about the chemical composition of approximately 250 000 wild and little-used species. Amongst these there may be many that could provide us with cheap and plentiful new sources of essential nutrients that could be of enormous benefit to those suffering not only from full-blown deficiency diseases but also suffering sub-normal health due to partial deficiencies. The destruction of much of the world's wilderness areas has already deprived us of the opportunity to evaluate the contributions that a great many plant species might have made towards the elimination of deficiency diseases. Many plants used as human foods contain compounds that are toxic to man. If intake is sufficiently high, these toxins may cause disease. Breeding programmes designed to eliminate toxins from crops species or reduce their concentrations to acceptable levels depend on genetic variability within the species or the possibility of producing hybrids with the desired characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗