Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By using leukotriene D4 (LTD4)-labeled alkaline phosphatase (LTD4-AP) and a mouse monoclonal anti-sulfidoleukotriene (sLT) antibody (1A-LDR1), we developed a solid-phase competition ELISA for sLTs. The detection limit of this assay was 6.3 +/- 1.2 pg sLT/100 microliters (mean +/- SEM; n = 10). Intraassay variations at 15, 50 and 150 pg sLT/well (9.8, 13.5 and 12.3%, respectively), the corresponding interassay variations (32.1, 11.9 and 18.8%, respectively) and the good correlation with a commercial radioimmunoassay (r = 0.97; n = 43) confirmed the validity of this ELISA. Furthermore, the assay had a low background and gave a 70-90% recovery of LTD4 added to medium containing up to 10% serum. In contrast to another sLT ELISA using the same antibody but based on competition with solid-phase LTE4-BSA, our assay is about 7-fold more sensitive. It also requires about 40 times less leukotriene for conjugate production than the previous method for the same number of determinations. The assay allows measurement of sLTs generated by small numbers of basophils present in isolated mononuclear cells or diluted whole blood in response to allergen, and allows simple and rapid determination of basophil reactivity to suspected allergens.
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PMID:Simplified sulfidoleukotriene ELISA using LTD4-conjugated phosphatase for the study of allergen-induced leukotriene generation by isolated mononuclear cells and diluted whole blood. 798 80

Cholestasis is the predominant complication in patients with total parenteral nutrition-related liver disease. Ursodeoxycholic acid has been reported to be beneficial for patients with various chronic cholestatic liver diseases. The aim of this prospective study was to determine the effects of short-term administration of ursodeoxycholic acid in nine patients (mean age 54 years) treated with home total parenteral nutrition (31 +/- 2 (mean +/- SEM) kcal/kg per day) for 13.9 +/- 5.2 months for short bowel syndrome; all presented biological evidence of hepatic cholestasis (mean alkaline phosphatase activity 5.2 times the upper limit of the normal) which appeared during nutrition; there was no cause of hepatic dysfunction other than total parenteral nutrition. Patients received 11.2 +/- 0.8 mg/kg per day of ursodeoxycholic acid orally for 1 (n = 9) or 2 (n = 5) 2-month periods, each of which was followed by a 2-month wash-out period. Liver function tests were performed before and at the end of each period. Compared with non-treatment periods, the two periods of ursodeoxycholic acid administration induced a significant reduction in gamma-glutamyl transpeptidase (27.1% and 20.4% respectively; p = 0.001) and alanine aminotransferase serum activities (7.0% and 34.8% respectively; p = 0.01) from baseline values. Alkaline phosphatase activity (p = 0.09), aspartate aminotransferase (p = 0.11) and bilirubin (p = 0.75) serum activities underwent no significant change during the study. These preliminary results strongly suggest that short-term ursodeoxycholic acid administration leads to biochemical improvement in liver function tests in patients with total parenteral nutrition-related liver disease.
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PMID:Is ursodeoxycholic acid an effective therapy for total parenteral nutrition-related liver disease? 800 5

We sought to assess efficacy and safety of a new oral formulation (tablet) of tiludronate in Paget's disease of bone. We studied 128 patients with Paget's disease in an open-label uncontrolled trial. Patients received a daily dose of 400 mg oral tiludronate (two tablets). Treatment was for 6 months. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatine (OH/Cr) were measured every 3 months, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self-evaluated from a visual analog scale (VAS). Statistical analysis revealed a significant reduction from baseline in SAP and OH/Cr levels, as well as VAS scores. In the whole population with evaluation under treatment, there was a reduction in initial SAP activity after 3 months (47.2 +/- 2.2%, mean +/- SEM) and 6 months (58.3 +/- 2.3%). In the population with SAP levels above twice the upper limit at inclusion and with evaluation at month 3 and month 6 (n = 96), the reduction in SAP levels was 49.3 +/- 2.4% after 3 months and of 59.5 +/- 2.6% after 6 months (ANOVA time effect, p = 0.0001). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance was good. Exhaustive biochemical investigation failed to reveal significant toxicity of tiludronate tablets at the dose of 400 mg/day. The dose of 400 mg daily of this new formulation appears to be a satisfactory tiludronate regimen for the treatment of Paget's disease of bone.
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PMID:Efficacy and tolerability of a new formulation of oral tiludronate (tablet) in the treatment of Paget's disease of bone. 805 89

At the onset of the mineralization of bone, small membranous matrix vesicles are often observed. The information available on the production and release of these vesicles is limited. When treated with 10-20 nM of the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), the human osteosarcoma cell line U-2 OS developed long cytoplasmic processes connecting adjacent cells. SEM and TEM show that TPA triggers a production and release of matrix vesicle-like membrane vesicles, mainly from the cellular processes. Tetracycline HCl was used to label intracellular bound calcium. The tetracycline HCl label was primarily localized to the end-feet of the cytoplasmic processes, indicating that these contain high concentrations of Ca2+, and to endoplasmic reticulum-like structures in the cell bodies. Together with our previous demonstration of the release of alkaline phosphatase-containing vesicles into the culture medium (Ringbom-Anderson T, Akerman KEO 1992 Calcif Tissue Int 50:533-540), the results presented here indicate that TPA induces a rapid induction of the primary steps of mineralization in U-2 OS osteosarcoma.
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PMID:Production and release of matrix vesicles in the cell processes of TPA-treated human osteoblast-like cells. 805 95

It has been hypothesized that the corticotropin-releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus (PVN) become hyperactive with age, and even more so in Alzheimer's disease. This hyperactivity could be due to an increased production of CRH per neuron, or an increased number of PVN neurons producing CRH, or both. As a first step in elucidating which of these biological mechanisms might be operative, we have estimated the absolute number of CRH immunoreactive neurons in the PVN of 10 human control subjects between 36 and 91 years of age and 10 Alzheimer patients between 40 and 97 years of age. CRH neurons were immunocytochemically detected in 6 microns paraffin sections with the aid of a highly specific monoclonal antibody to CRH. The antibody signal was amplified by the biotin-streptavidin and alkaline phosphatase methods. The absolute number of CRH neurons in the PVN was obtained by multiplying the number of CRH neurons in a unit volume (NV) by the total volume of the PVN. Two different methods were used to estimate the NV: an unfolding method and a disector method (about three times more time-consuming). Compared to the disector, the unfolding method consistently yielded a lower cell number for all patients by 38% (+/- 2.8%; mean +/- SEM). However, both methods yielded an increase in the absolute number of CRH neurons in control and Alzheimer patients with age. No statistically significant difference in the absolute number of CRH neurons was found between control and Alzheimer patients with both methods. The age-dependent increase in the absolute number of CRH neurons within the PVN of both control and Alzheimer patients is interpreted as a sign of activation of the CRH neurons with age.
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PMID:Age-related increase in the total number of corticotropin-releasing hormone neurons in the human paraventricular nucleus in controls and Alzheimer's disease: comparison of the disector with an unfolding method. 813 71

This study was carried out in order to evaluate serum carboxy-terminal propeptide of human type I procollagen (PICP) in patients with primary hyperparathyroidism and to examine its changes following parathyroidectomy. Seventeen patients (four males and 13 famels, aged 53.8 +/- 3.1 SEM years) were studied in basal conditions; six patients also were investigated after successful parathyroid surgery. Mean serum PICP values of patients with primary hyperparathyroidism (194.5 +/- 27 SEM micrograms/l) were significantly higher (p < 0.001) with respect to those found in normal subjects. However, deviations from the norm (Z score values) were significantly less with respect to deviations of serum osteocalcin, alkaline phosphatase and urinary hydroxyproline/creatinine ratio. Following parathyroidectomy, it was possible to observe a discrepancy between markers of bone resorption and those of bone formation. The former tend to decrease, while the latter either do not show any significant change (serum alkaline phosphatase and serum osteocalcin) or increase (serum procollagen). The results of our investigation indicate that in basal conditions the assay of serum procollagen may be of clinical value but it would be better to use it in combination with other biomarkers of skeletal remodelling. The results obtained after parathyroidectomy are the opposite of those obtained following parathyroid hormone infusion and should be ascribed to the effect of acute hormone deficiency on collagen synthesis. The positive biochemical uncoupling following surgery might lend support to the rise of bone mineral density consistently reported in the first few months following parathyroidectomy.
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PMID:Serum carboxy-terminal propeptide of human type I procollagen in patients with primary hyperparathyroidism: studies in basal conditions and after parathyroid surgery. 820 59

In this study, we evaluated the effect of long-term administration of daily calcium carbonate (2-4 g/day) and intermittent high oral doses of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3, 3-4 micrograms, given twice a week] in conjunction with a 3-mEq/1 calcium concentration in the dialysate for the treatment of severe secondary hyperparathyroidism in 6 hemodialysis patients. All patients had reduced serum levels of 1,25-(OH)2D3, which increased significantly (p < 0.005) reaching the maximum level in the 4th month. Serum total and ionized calcium levels significantly increased also, in relation to those before treatment. No patients developed hypercalcemia. Serum phosphorus did not significantly change during the study. Initial serum intact parathyroid hormone (PTH) (1,241 +/- 233 pg/ml, mean +/- SEM) markedly decreased after starting treatment with 1,25-(OH)2D3, being 542 +/- 174 pg/ml in the 5th month and 477 +/- 174 pg/ml in the 8th month. These changes are statistically significant (p < 0.05 and < 0.007, respectively). Alkaline phosphatase behavior was similar to that of intact PTH. A constant direct correlation between intact PTH and alkaline phosphatase and an inverse significant correlation between intact PTH and 1,25-(OH)2D3 was evidenced by us. We conclude that oral 1,25-(OH)2D3 pulse therapy is very effective in suppressing PTH secretion. The administration of calcium carbonate and the use of dialysate with a reduced calcium concentration would allow to prevent hyperphosphatemia and the administration of high oral doses of 1,25-(OH)2D3 without concomitant hypercalcemia.
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PMID:Treatment of severe secondary hyperparathyroidism with administration of calcium carbonate, intermittent high oral doses of 1,25-dihydroxyvitamin D3 and dialysate with 3 mEq/1 calcium concentration. 834 82

High calcitonin levels have been reported in chronic renal failure. To study the C cell response in patients with chronic renal failure, an intravenous bolus of pentagastrin was administered to 11 patients and 11 healthy subjects. Samples were obtained at 0, 1, 2, 3, 5 and 10 min for calcitonin assay. In order to detect only the active monomeric calcitonin, an immunoradiometric assay method was used. The influence of calcium, phosphate, alkaline phosphatase and intact parathyroid hormone was also evaluated. Although basal calcitonin levels were higher (p < 0.01) in chronic renal failure (mean +/- SEM: 10.1 +/- 2.9 pmol/l) versus healthy subjects (1.1 +/- 0.3 pmol/l), the area under the curve showed there to be no differences between the two groups. The rising branch of the area under the curve, employed as an expression of the C cell response capacity, showed no differences either (chronic renal failure vs healthy subjects: 5.6 +/- 2 vs 2.6 +/- 0.7 pmol l-1 min-1, p = 0.28). In the chronic renal failure group, a positive correlation was found (r = 0.625, p < 0.05) between the rising branch of the area under the curve and parathyroid hormone. We conclude that monomeric calcitonin is increased in chronic renal failure, but C cells of the thyroid respond to pentagastrin, as they do in normal subjects. This finding is of great clinical importance when a patient with renal impairment is evaluated for medullary thyroid carcinoma. The calcitonin response to pentagastrin seems to be related directly to the degree of secondary hyperparathyroidism in chronic renal failure.
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PMID:Normal calcitonin response to pentagastrin stimulation in patients with chronic renal failure. 835 57

Running is a popular sport, but in some studies long distance running in women has been related to reduced bone mass and a potential risk of osteoporosis. To investigate the impact of running on bone mass in men, 120 healthy, physically active men (19-56 yr old; running 0-160 km/week) were studied. Bone mineral content was measured in the lumbar spine, total body, and proximal femurs by dual energy x-ray absorptiometry and in the forearm by single photon absorptiometry. Bone turnover was assessed by urinary pyridinium cross-links, plasma osteocalcin, and serum alkaline phosphatase. Lumbar bone mineral content was negatively correlated to the weekly distance run (r = -0.37; P < 0.0001), with a difference of 19 +/- 5% (mean +/- SEM) between controls and elite runners. A similar relation was found for all measurement sites. After adjustment for possible confounders, the correlations remained statistically significant in areas with a high proportion of trabecular bone. Bone turnover parameters were 20-30% higher in the elite runners, whereas sex hormone status was unrelated to running activity. We conclude that male long distance runners had reduced bone mass and increased bone turnover compared to controls, which suggests accelerated bone loss. The pathophysiological explanation was not clear, but sex hormones did not seem to play a key role.
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PMID:Low bone mass and high bone turnover in male long distance runners. 837 Jun 98

An intrinsic phosphate (Pi) transport defect in the proximal tubule (PT) presumably underlies X-linked hypophosphatemic rickets. We recently reported normal Pi transport in the S1 segment of the Hyp mouse PT. Whether Pi wasting results from an abnormality in the S2 or S3 segment remains unknown. Thus, we compared Pi transport in S2 and S3 immortalized cells from transgenic (simian virus 40) normal and Hyp mice. These cells display biochemical features of PT cells, including alkaline phosphatase- and hormone- stimulated cAMP activity as well as gluconeogenesis. Moreover, kinetic studies in S2 cells reveal a similar Km[0.26 +/- 0.03 (+/-SEM) vs. 0.22 +/- 0.03 mM] and maximum velocity (Vmax; 5.5 +/- 0.66 vs. 5.9 +/- 0.72 nmol/mg x 5 min) in normal and Hyp mice, respectively. Km and Vmax were also similar in cells from the S3 segment; however, the Vmax values in S3 cells in normal and Hyp mice (2.8 +/- 0.45 and 3.0 +/- 0.56 nmol/mg x 5 min) were reduced in both animal models compared to those in S2 cells (P < 0.001), whereas the Km values in S3 cells from normal and Hyp mice (0.10 +/- 0.02 and 0.11 +/- 0.04 mM) were increased relative to those in S2 cells (P < 0.001). These data indicate that Pi transport throughout the PT of Hyp mice is intrinsically normal. Such observations exclude the presence of a nascent defect in renal Pi transport in the kidneys of Hyp mice and support the hypothesis that a humoral abnormality underlies X-linked hypophosphatemic rickets.
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PMID:Normal phosphate transport in cells from the S2 and S3 segments of Hyp-mouse proximal renal tubules. 860 7


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