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At least 919 records · Page 51Linked to original sources
PubMed1975

1,25-dihydroxyvitamin D3 and 1, alpha-hydroxyvitamin D3 in children: biologic and therapeutic effects in nutritional rickets and different types of vitamin D resistance.

This investigation confirms the high level of biologic activity and the similarity of the effects of small doses of 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) and of its analog 1alpha-hydroxyvitamin D3 (1alpha-OH-D3) on children with nutritional rickets, "pseudodeficiency" rickets (PDR), hereditary hypophosphatemia, chronic idiopathic hypoparathyroidism, and chronic renal failure. It also shows that cystinotic patients may develop, at the end stage of the disease, a certain degree of resistance to 1,25-(OH)2-D3. The comparison of the therapeutic effects of long term oral administration of 1,25-(OH)2-D3 or 1alpha-OH-D3 to two D-deficient children and two sibs with PDR demonstrates differences in sensitivity. In the patients with nutritional rickets, 0.5 mug/24 hr of either drug corrects the biochemical abnormalities, initiates healing of skeletal lesions in 28 days, and cures the metaphyseal le lesions in 60 days of therapy. In contrast, it appears that doses of either drug that are curative in D deficiency rickets are only partly active in PDR. These observations indicate that the hypothesis of a deficit in 25-hydroxycholecalciferol 1alpha-hydroxylase in patients with PDR must await for confirmation more direct evidences, and that such a deficit, even if proven, may not account for all of the biochemical and skeletal alterations seen in patients with this inherited disorder.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1980

Modulation of the intracellular cystine content of cystinotic fibroblasts by extracellular albumin.

Cystinotic fibroblasts contain highly elevated amounts of intracellular non-protein cystine reaccumulation by cystine-depleted cystinotic fibroblasts and the steady-state cystine content of nondepleted cystinotic fibroblasts can be modulated by the addition of bovine serum albumin to the culture medium. This effect is not seen in cultures of normal and cystinotic heterozygote fibroblasts. The cystinotic homozygote cells accumulate cystine under there conditions from proteolysis of the albumin. An increased rate of pinocytosis or proteolysis of albumin does not account for the observed cystine accumulation by the cystinotic fibroblasts. Comparison of the amount of cystine accumulated to the amount of albumin degraded shows that less than one percent of the cystine moieties released by proteolysis is retained within these cells.

Cells, Cultured↗
PubMed1981

Cystinotic fibroblasts are depleted of free-cystine by acid pH medium.

The free (nonprotein) cystine content of human cystinotic fibroblasts was found to vary with the pH of their culture medium. Intracellular cystine content was highest at alkaline medium pH's and lowest at acidic medium pH's. When maintained in medium of pH 6.3, cystinotic fibroblasts lost 50% of their free-cystine content in 6 hr and over 95% in 30 hr. Cystine was the only amino acid to show significant variation with changes in the pH of the culture medium.

Child↗
PubMed1982

Cystinotic and normal fibroblasts: differential protection in cystine-free medium by dithiothreitol.

We studied survival of normal (n=4) and cystinotic (n=3) fibroblast strains in selective (cystine-free) medium, with or without dithiothreitol (DTT)-thiol or disulfide. Cells were plated at low density first in maintenance medium (containing cystine), then washed and exposed to selective medium for 24 hr or longer. Cultures were trypsinized at specified times and the cells counted. Selective medium caused progressive detachment (greater than 90% by 72 hr) of control and cystinotic cells: DTT-disulfide (4 mM) and DTT-thiol (0.5 mM) both protected cystinotic cells (p less than 0.02) but not control cells in selective medium. DTT-thiol (0.5 mM) and DTT-disulfide (4mM) both depleted the intracellular non-protein cystine pool of cystinotic cells to less than 25 percent of pretreatment levels. Cystinotic cells preincubated with cysteamine (1 mM X 4 hr) to deplete the intracellular cystine pool were not protected by DTT-disulfide than with DTT-thiol. These findings imply that mobilization of intracellular cystine protects cystinotic cells in selective medium; cystinotic fibroblasts can utilize DTT-disulfide as well as DTT-thiol to mobilize cystine.

Culture Media↗
PubMed1985

Altered oxidative metabolism, motility, and adherence in phagocytic cells from cystinotic children.

The present study investigates whether the metabolic abnormalities in cystinotic cells could affect nonspecific immune responses. Lymphocytes showed normal antibody-dependent cellular cytotoxicity and natural killer activity. However, cystinotic polymorphonuclear and mononuclear phagocytes exhibited altered oxidative responses as monitored by a luminol dependent chemiluminescence (CL) assay. Both isolated polymorphonuclear and mononuclear phagocytes in the absence of stimuli showed significantly increased CL production which was not found when cells were tested directly within whole blood. CL responses to a panel of stimuli differed markedly according to the type of cells and agents tested. Indeed, isolated polymorphonuclear demonstrated increased CL responses to soluble but not particulate agents, whereas isolated mononuclear phagocytes and overall cell CL responses in whole blood were found to be within the normal range regardless of the type of stimulus used. We also studied some membrane related properties of phagocytic cells. Fc and C3b receptors were normally expressed as tested by erythrocyte-antibody and erythrocyte-antibody-complement rosette-forming cells. Nevertheless, cystinotic polymorphonuclear and mononuclear phagocytes presented decreased random and directed migrations in an under-agarose chemotaxis assay. Finally, cystinotic granulocytes showed an impaired adhesiveness in a nylon fiber assay.

Cell Adhesion↗
PubMed1992

Intracellular cystine loading causes proximal tubule respiratory dysfunction: effect of glycine.

The present study examined proximal tubular respiration in control proximal tubules and proximal tubules loaded with cystine using 2 mmol/L cystine dimethyl ester. Basal oxygen consumption was significantly less in cystine-loaded tubules (20.6 +/- 0.5 versus 12.1 +/- 0.6 nmol O2.min-1.mg protein-1, p < 0.001). In the presence of 10(-4) mol/L ouabain, an inhibitor of the NaK ATPase, oxygen consumption was 10.2 +/- 0.7 nmol O2.min-1.mg protein-1 in control tubules and 11.4 +/- 1.0 nmol O2.min-1.mg protein-1 in cystine-loaded tubules. Thus, proximal tubular intracellular cystine loading specifically inhibits oxygen metabolism directed toward transport. Compared with control proximal tubules, cystine-loaded proximal tubules also had a lower rate of O2 consumption when the cells were permeabilized to sodium with nystatin and when mitochondrial respiration was uncoupled. Glycine, an amino acid that is cytoprotective to hypoxic proximal tubule injury, ameliorated the respiratory dysfunction observed in cystine-loaded tubules.

Animals↗
PubMed1985

Blunted prolactin response to thyrotropin-releasing hormone stimulation in cystinotic children receiving cysteamine.

We investigated whether long term cysteamine therapy in cystinotic children altered their basal and stimulated serum PRL levels. Five subjects who had normal plasma PRL responses to TRH stimulation before cysteamine treatment each had a lower basal PRL level and a blunted PRL response during long term (19-59 months) cysteamine therapy. A blunted PRL response was not found in 12 cystinotic subjects of the same age and stage of disease who had not received cysteamine. The effect on PRL release was not found in 2 subjects who received short term (1-2 weeks) treatment with full-dose cysteamine (50 mg/kg . day). The TSH response to TRH stimulation was not blunted during long term cysteamine therapy. These findings suggest that cysteamine alters PRL secretion in humans.

Administration, Oral↗