Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of tri-iodothyronine (T3) and insulin-like growth factor-I (IGF-I) on [3H]thymidine incorporation, alkaline phosphatase (ALP) activity and IGF-I receptor mRNA levels were studied in rat epiphyseal chondrocytes cultured in monolayer. Chondrocytes from enzymatically digested rat tibia epiphyseal growth plates were seeded in monolayer culture and precultured for 7-14 days in Ham's F-12 medium supplemented with 10% (v/v) newborn calf serum and 1% (v/v) of a serum substitute. After preculture the medium was changed to Ham's F-12 medium containing 1% (v/v) serum from hypophysectomized rats, and the effects of T3 and/or IGF-I on DNA synthesis ([3H]thymidine incorporation), ALP activity (a late marker of differentiated epiphyseal chondrocytes) and IGF-I receptor mRNA levels were studied. ALP activity was increased by T3 in a dose-dependent manner with a maximal response at 10 micrograms T3/l (678 +/- 86% compared with control culture). The increase in ALP activity was accompanied by a concomitant decrease in [3H]thymidine incorporation (52 +/- 14% compared with control culture). Human GH (hGH; 50 micrograms/l) and IGF-I (25 micrograms/l) had no stimulatory effect on ALP activity. However IGF-I (10 micrograms/l) exerted an inhibition on the T3 (10 micrograms/l)-induced increase in ALP activity (64 +/- 9% compared with T3-treated culture). T3 (3 micrograms/l) inhibited the increase in [3H]thymidine incorporation caused by 25 micrograms IGF-I/l (51 +/- 13% compared with IGF-I-treated culture). Furthermore, IGF-I receptor mRNA levels were increased by 10 micrograms T3/l (137 +/- 4.2% compared with control culture) while no effect of hGH (50 micrograms/l) or IGF-I (25 micrograms/l) was demonstrated. Both T3 and IGF-I were shown to interact with epiphyseal chondrocytes and both substances seemed to affect cell proliferation and maturation and therefore longitudinal bone growth. Furthermore, the results indicated that IGF-I is important for proliferation of the cells while T3 initiates the terminal differentiation of epiphyseal chondrocytes.
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PMID:Effects of tri-iodothyronine and insulin-like growth factor-I (IGF-I) on alkaline phosphatase activity, [3H]thymidine incorporation and IGF-I receptor mRNA in cultured rat epiphyseal chondrocytes. 143 76

Fifteen prepubertal short stature children (10 girls, 5 boys), mean age 9.6 years (range 5.2-12.7 years), with normal response to growth hormone stimulation tests (group A) or partial growth hormone deficiency (GHD) of idiopathic nature (group B) were included in a controlled longitudinal study for evaluation of predictive parameters for the long-term growth response after administration of biosynthetic human growth hormone (B-hGH). The average knee-heel length velocity for the first 3 months was significantly correlated to total body height velocity during the following 9 months (p less than 0.0008). By contrast, this association could not be found for height velocity during the same period. The increase in serum values of alkaline phosphatase and insulin-like growth factor I (IGF-1) during the first month of treatment was not significantly correlated to height velocity during the first year. During one year of treatment with B-hGH the mean height velocity for groups A and B increased from 4.4 cm/year (range 2.5-6.5) to 7.6 cm/year (range 4.7-10.6). Bone age advanced by 1.08 +/- 0.60 per chronological year. The ratio between total height and knee-heel length prior to treatment was 3.34 +/- 0.10 and after one year 3.33 +/- 0.10, suggesting a proportional linear growth. An inverse relationship was observed between the ratio and chronological age. In conclusion, early knee-heel measurement may be a useful non-invasive predictor of long-term linear growth in children during treatment with growth hormone, and the ratio of total height to lower leg length may be of importance in detecting dysproportional growth.
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PMID:Predicting and monitoring of growth in children with short stature during the first year of growth hormone treatment. 178 87

Studies were conducted to determine the in vitro effect of selected food components on activity of the brush border membrane pteroylpolyglutamate hydrolase (folate conjugase) of porcine and human intestine. Foods differed widely in their effects although the pattern of the effects on both porcine and human enzymes was similar. Extracts of legumes, tomatoes, and orange juice consistently inhibited the conjugase activity. Citrate was also inhibitory to some extent. In contrast, extracts of cereal grain flours, whole egg, milk, cabbage, cauliflower, and lettuce caused little inhibition. Purified phytohemagglutinins, soybean trypsin inhibitors, and bovine milk folate-binding protein had no effect on the conjugase activity at the concentrations tested. The food substances that inhibited the conjugase activity did not bind the polyglutamyl folate substrate or inhibit intestinal brush border membrane sucrase and alkaline phosphatase. These findings suggest that food composition may influence folate bioavailability by interfering with the intestinal deconjugation of dietary polyglutamyl folates.
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PMID:Inhibition by selected food components of human and porcine intestinal pteroylpolyglutamate hydrolase activity. 229 33

To explain frequent discordances between serum GH levels and clinical manifestation of acromegaly, we investigated the possibility that certain immunoglobulins G (IgGs) might be responsible for the displacement of [125I]human (h) GH in the hGH RIA. We incubated dilute sera from seven active acromegalics (basal immunoreactive hGH, 22-313 micrograms/L) with rat adipocyte plasma membranes adsorbed on polystyrene plates. IgGs that bound to GH receptor sites in the absence and presence of 250 nM hGH (for nonspecific binding) were detected using anti-hIgG (Fc-specific) antibody conjugated with alkaline phosphatase. In this system two of the seven sera studied tested positive for IgGs against GH-binding sites (serum 4 in 1:400 dilution, and serum 7 in 1:10 dilution). We studied further the serum with the highest titer. On Sephadex G-100, most of the GH-like immunoreactivity (assayed by RIA) present in serum 4 coeluted with IgGs (assayed by immunodiffusion) as a high mol wt (greater than or equal to 150 kDa) component. To confirm its IgG nature, this material was then adsorbed on protein-A-Sepharose and eluted with 0.1 M sodium citrate, pH 3.0. The protein-A-purified IgGs from serum 4 bound specifically to GH receptor sites in adipocyte membranes and displaced [125I]hGH in the hGH RIA. In contrast, IgGs purified from another acromegalic patient (313 micrograms/L hGH) repeatedly tested negative in the membrane binding assay and hGH RIA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Certain large forms of circulating immunoreactive human growth hormone are in fact immunoglobulins. 230 22

All batches of Met-hGH examined stimulated statural growth to approximately the same extent. The growth rates measured partly exceeded the results obtained in previous studies with pituitary preparations in the same dosage. Under treatment with SI, i.e. the preparation with the highest amount of ECP, high antibody titres with high binding capacity against GH and ECP were found. With SII all antibody determinations showed much lower titres. With Somatonorm (SIII), in the large majority of cases no antibodies were detectable. The titres registered in a few children were low and the binding capacities were negligible. The biologically determined somatomedin activity was initially pathologically low. During treatment it rose to supraphysiological levels. Also the radioimmunologically assayed somatomedin and the alkaline phosphatase increased significantly. At the start of the first series, two patients showed allergic skin reactions which turned out to be caused by the insufficiently purified preparations. Therapy with extractive preparations was free of such side-effects and fully successful. Both of the patients were atopic. A third child who was also allergic developed after 6-9 months the highest antibody titres seen, combined with a high binding capacity. Also, with this boy, treatment was switched over to pit-hGH, with very good results. Two children with pituitary dwarfism already developed in utero high antibody titres against Met-hGH but not against ECP. For this response, neither the Somatonorm nor its impurities can be implicated. Rather, it is the reaction to GH generally, which the organism recognizes as a foreign protein and thus as an antigen. One of the patients stopped growing after nine months. Likewise, pituitary GH did not lead to any further improvement.
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PMID:Recombinant human growth hormone. 242 93

Over 3 1/2 years, 54 previously untreated hypopituitary children were enrolled in three studies; 48 had idiopathic pituitary dwarfism. Three preparations of somatrem were used (SI, SII, Somatonorm). Growth velocities on all three preparations were similar, though SI and SII tended to produce slightly higher growth velocities. Serum somatomedin and alkaline phosphatase levels increased during treatment. Antibodies to Escherichia coli polypeptide (ECP) increased to a maximum Z score of about 0.7 with SI, but this was considerably lower with SII and below 0.1 with Somatonorm. Anti-hGH antibodies had the highest titre in children treated with SI and these antibodies also had quite high binding capacities. Anti-hGH antibody formation was negligible during Somatonorm treatment.
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PMID:Treatment of pituitary dwarfism with biosynthetic growth hormone. 329 34

A study of 31 children with short stature was initiated in 1982. They received subcutaneous injections of pituitary hGH, 0.1 IU/kg/day; no adverse effects were seen and none of the patients acquired antibodies. Only the results of the first year are presented, as final height has not yet been attained. A high growth response was seen in 29 of the 31 children; they experienced an initial rise of IGF-1, IGF-2, alkaline phosphatase and procollagen III. The best response was obtained in the child with the lowest levels of endogenous pulsatile hGH secretion.
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PMID:Growth hormone treatment in short children. 329 40

During the period from 1982 to 1985, biosynthetic growth hormone (methionyl-hGH) was administered to 55 children with pituitary growth deficiency, 49 with idiopathic, six with other forms of the disorder. Preparations with a relatively high content of Escherichia coli polypeptides (ECP) were given to 32 children (group I), those with a markedly reduced ECP content to 12 (group II), while 11 children received almost ECP-free preparations (group III). The treatment achieved an intensive rise of growth acceleration in all three groups. At the same time, somatomedin C, biological somatomedin activity and alkaline phosphatase rose steeply, reaching a maximum after six months and remaining at high concentrations even thereafter. High antibody titres against ECP and hGH (with high binding capacity) were demonstrated in group I children, significantly lower titres with little binding capacity in those of group II, while most of those in group III had no measurable antibodies. Even in high concentrations the antibodies did not have any inhibiting effect on growth. No positive correlation between antibody titre and growth velocity was demonstrable. An exception was a boy with an allergy in group I, who had a maximal antibody titre and, at the same time, a high serum concentration of IgE. He had marked delay in growth which, however, quickly became normal on administration of extractive hGH.
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PMID:[Therapy of pituitary dwarfism with recombinant human growth hormone. A multicenter study]. 351 93

The ability of eight stripping agents to solubilize five marker enzymes from rat renal brush border membranes isolated by three different preparative methods was examined. Protein and enzyme activities - alkaline phosphatase (APase), L-leucine aminopeptidase (LAPase), gamma-glutamyl transpeptidase (GGTase), gamma-glutamyl hydrolase (GGHase) and maltase - solubilized by the treatments were expressed as percent of total activity recovered in excess of control values. The relative enzyme activity and the solubilization factor were determined for each marker enzyme in every treated sample and the treatments with the eight agents compared. Trypsin treatment released > 80% of LAPase and < 10% of total membrane protein. Papain treatment released only 16--23% of total membrane protein but most of the enzyme activities except APase. Neuraminidase had no solubilizing effect. 4--10% of total membrane protein was solubilized by LiCl treatment but no marker enzyme activities were released. Less total membrane protein was released by treatment with proteolytic enzymes or LiCl than with the detergents Triton X-100, hexadecyltrimethylammonium bromide, sodium deoxycholate, and sodium dodecylsulfate. APase activity was the least readily solubilized. Correlating the degree of solubilization for five marker enzymes with the types of stripping agents used and with the appearance of the membrane surface when examined by electron microscopy led to the suggestion that LAPase, GGTase, GGHase and maltase molecules are part of an interwoven surface layer of membrane proteins which can be disrupted by transamidation and transesterification reactions. APase appears to be more strongly associated with the intact lipid matrix than the bulk of the membrane protein.
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PMID:Ease of solubilization of five marker enzymes in three preparations of rat renal brush border membranes. 610 74

Growth hormone receptor (GH-R) gene expression was evaluated in avian growth-plate cartilage by Northern blot and hybridization using the avian GH-R probe. A single transcript of approximately 5.2 kb was demonstrated in cultured growth-plate chondrocytes as well as in growth-plate extracts. GH receptor gene expression was inhibited by chicken GH (cGH) in a dose- and time-dependent manner. Chicken GH was more potent in down-regulating the GH-R gene expression than hGH, but on the other hand cGH exhibited a lower affinity to avian chondrocytes receptor than did the human hormone. Addition of ascorbic acid to the culture media caused cell differentiation: induction of alkaline phosphatase activity and attenuation of collagen type II gene expression. No differences in the GH-R gene expression were observed in the nondifferentiated cells compared with the differentiated cells. Chicken GH did not form any complex with the purified hGH binding protein (hGHBP), did not bind to human lymphocytes GH receptor, and did not affect Nb2 cell proliferation. These systems represent somatogenic and lactogenic types of GH receptors, respectively. In summary, avian growth-plate chondrocytes in situ and in culture exhibit GH-R and these receptors are capable of binding GH. Thus, the failure of GH to affect avian chondrocytes' proliferation was not due to either the absence of receptors on the cell membrane or to a lack in its binding activity, but rather may be due to events farther downstream.
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PMID:Growth hormone receptors in avian epiphyseal growth-plate chondrocytes. 750 82


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