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)

Plasmids are involved in the biosynthesis of many microbial secondary metabolites, and compounds which have various chemical structures are produced by microorganisms. Therefore, it is possible to find microbial products which have no antimicrobial activities but pharmacological activities. Aminopeptidases, alkaline phosphatase and esterase have been found to appear on the cell surface and their strong inhibitors have been confirmed to enhance or decrease immune response. These inhibitors have a very low toxicity without cytotoxic action. Bestatin, which inhibited aminopeptidase B and leucine aminopeptidase, enhanced delayed-type hypersensitivity in a wide range of its low dosis (0.1-100 micrometer/mouse) and produced an immune resistance to the second inoculation of the same tumor cells. It showed a synergistic action with antitumor agents in treatment of experimental tumors. Treatment with bestatin alone exhibited a strong therapeutic effect on slowly growing solid tumors.
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PMID:Small molecular microbial products enhancing immune response. 65 81

Some biological and neurochemical properties of the venom of stonefish (Syanceja horrida) were investigated. The venom exhibited oedema-inducing, haemolytic, hyaluronidase, thrombin-like, alkaline phosphomonoesterase, 5' nucleotidase, acetylcholinesterase, phosphodiesterase, arginine esterase, and arginine amidase activities. Recalcification clotting time, prothrombin, and kaolin-cephalin clotting times were increased 1.7-2.3- and 2.4-fold respectively. The LD50 (i.v. mouse) was 300 micrograms/Kg. Its effects on uptake and stimulation of neurotransmitter synthesis and release were observed in rat brain synaptosomes. In the presence of 100 micrograms venom, uptake of [methyl-3H] choline in rat brain synaptosomes was inhibited 70%, while that of 4-amino-n-[U-14C] butyric acid was inhibited 20%. The toxin also stimulated the release of [3H]-acetylcholine from the synaptosomes.
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PMID:Biological activities of Synanceja horrida (stonefish) venom. 136 68

A method is described for isolating Clara cells from the mouse lung that does not require the technique of elutriation. Mouse lungs totally perfused of blood are instilled with crystalline trypsin (0.25%) and incubated for the optimum time of 15 min. The lung tissue is chopped, mechanically agitated, and sequentially filtered to obtain a primary digest of 3 to 5 x 10(6) cells. Clara cells, identified routinely by histochemical localization of NADPH diaphorase, using the stain nitrotetrazolium blue (NBT), accounts for between 20 to 40% of the cells in the primary digest. Layering the cells of the primary digest on a discontinuous Percoll gradient followed by centrifugation gives rise to a major band of cells, 52% that are Clara cells (0.77 +/- 0.28 x 10(6)/mouse). A second method was devised to purify the Clara cells by simply centrifuging (32g, 6 min, 10 degrees C) the primary digest and discarding the supernatant that contained only a few NBT positive cells. When this process was repeated three times, the final pellet contained 68% Clara cells realizing 0.55 +/- 0.16 x 10(6) cells/mouse. The cells have typical Clara cell morphology as confirmed by electron microscopy and have a high level of P-450 enzymes (7-ethoxycoumarin deethylase and coumarin hydroxylase). Furthermore, the primary digests and the purified isolates contain less than 1% alveolar Type II cells, although such cells, identified by the histochemical localization of alkaline phosphatase, can be obtained by a second, more extensive digestion procedure. The simple procedure described for the isolation of mouse Clara cells could be further advanced if methods could be devised to prevent the loss of NADPH diaphorase activity during enzymatic digestion and cell centrifugation.
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PMID:Isolation of Clara cells from the mouse lung. 220 Jun 69

Changes in hepatic microsomal mixed-function oxidase enzyme levels (aniline hydroxylase, aminopyrine demethylase, glutathione S-transferase), glutathione content, total sulphydryl content, and plasma enzyme levels of aspartate transaminase, alanine transaminase and alkaline phosphatase were studied in male Swiss albino mice exposed to Salmonella typhimurium endotoxin (50-150 micrograms per mouse, LC50 141.82 micrograms). Animals exposed to the same dose of endotoxin but pretreated with protein A of Staphylococcus aureus (5 micrograms/per mouse) protected the animals from both mortality and depletion of biotransformation enzymes.
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PMID:Protein A protects mice from depletion of biotransformation enzymes and mortality induced by Salmonella typhimurium endotoxin. 268 31

The blood-brain barrier is a specific property of differentiated brain endothelium. To study the differentiation of blood vessels in the brain, we have correlated the expression of a number of proteins in brain endothelial cells with the development of the blood-brain barrier in mouse, quail, and chick embryos. Using histochemical methods, alkaline phosphatase activity was found to be present in all species and appeared around embryonic Days 17 (mouse), 14 (quail), and 12 (chick). Butyrylcholinesterase activity was found in the mouse and quail but not the chick brain vasculature, and appeared around Days 17 (mouse) and 15 (quail). gamma-Glutamyltranspeptidase activity was demonstrated histochemically in mouse but not in chick and quail brain capillaries, beginning at Day 15. Transferrin receptor was localized on brain endothelium in all species by immunofluorescence methods using monoclonal antibodies. It appeared at Days 15 and 11 in mouse and chick embryonic brain, respectively. The staining of all markers in embryonic brain was compared with adult brain endothelium and the leptomeningeal blood vessels. The expression of these proteins was correlated with the development of the blood-brain barrier by studying the permeability of brain endothelium for the protein horseradish peroxidase during mouse embryogenesis. Vessels in the telencephalon were found to become impermeable around Day 16 of development. Taken together the results of previous investigations and those presented here, we conclude that a number of proteins are sequentially expressed in brain endothelial cells correlating in time with the formation of the blood-brain barrier in different species.
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PMID:Differentiation-dependent expression of proteins in brain endothelium during development of the blood-brain barrier. 287 8

The LD50 in the rat and the mouse is about 1600 mg/kg (oral administration) and 75 mg/kg (rat) and 50 mg/kg (mouse) on intravenous administration. Subchronic oral studies over 13 weeks in doses of 5, 15 and 45 mg/kg/day in the dog and 50, 100 and 200 mg/kg/day in the rat have demonstrated minimal toxicity for midazolam, as for other benzodiazepines. High doses produced increased liver weight in the rat and the expected increases in alkaline phosphatase in the dog (species-specific reaction). Detailed blood and urine analyses as well as histological examination of organs produced no indication of changes relevant for man. Subchronic parenteral studies (i.v. and i.m. for five weeks) using up to 6 mg/kg/day in dogs and rats showed the compound to be not only systemically, but also locally, extremely well tolerated. Reproduction toxicology studies have shown that midazolam is neither embryotoxic nor teratogenic and that it has no effect on the fertility and post-natal development of animals. In the AMES test and the fluctuation test, midazolam had no mutagenic effect.
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PMID:Safety aspects of midazolam. 613 79

A radiation- and chemotherapy-resistant murine osteosarcoma was used to investigate the effect of local hyperthermia (42.5 +/-0.1 degrees, 30 min) alone and in combination with cyclophosphamide. The cytotoxicity of cyclophosphamide on murine osteosarcoma was established previously in our laboratory. Local hyperthermia (42.5 +/- 0.1 degree, 30 min) had little or no effect on the 16-day-old (206 X 10(6) osteosarcoma tumor cells/mouse) tumor as shown by the changes in the tumor cell marker, alkaline phosphatase. A 2.5 +/- 3.5% reduction in the number of tumor cells was seen. Large tumors treated at 21 days postimplantation (357 X 10(6) tumor cells) showed a reduction of 24 +/- 14%. The effect of combination treatment with cyclophosphamide and hyperthermia produced greater reduction in the numbers of tumor cells than did either treatment used alone.
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PMID:Reduction of tumor burden in a murine osteosarcoma following hyperthermia combined with cyclophosphamide. 658 5

Thyroid hormone (TH) responsive genes can be both positively and negatively regulated by TH through receptors (TR) alpha and beta expressed in most body tissues. However, their relative roles in the regulation of specific gene expression remain unknown. The TR beta knockout mouse, which lacks both TR beta1 and TR beta2 isoforms, provides a model to examine the role of these receptors in mediating TH action. TR beta deficient (TR beta-/-) mice that show no compensatory increase in TR alpha, and wild-type (TR beta+/+) mice of the same strain were deprived of TH by feeding them a low iodine diet containing propylthiouracil, and were then treated with supraphysiological doses of L-T3 (0.5, 5.5, and 25 microg/day/mouse). TH deprivation alone increased the serum cholesterol concentration by 25% in TR beta+/+ mice and reduced it paradoxically by 23% in TR beta-/- mice. TH deprivation reduced the serum alkaline phosphatase (AP) concentration by 31% in TR beta+/+ mice but showed no change in the TR beta-/- mice. Treatment with L-T3 (0.5 to 25 microg/mouse/day) caused a 57% decrease in serum cholesterol and a 231% increase in serum AP in the TR beta+/+ mice. The TR beta-/- mice were resistant to the L-T3 induced changes in serum cholesterol and showed increase in AP only with the highest L-T3 dose. Basal heart rate (HR) in TR beta-/- mice was higher than that of TR beta+/+ mice by 11%. HR and energy expenditure (EE) in both TR beta+/+ and TR beta-/- mice showed similar decreases (49 and 46%) and increases (49 and 41%) in response to TH deprivation and L-T3 treatment, respectively. The effect of TH on the accumulation of messenger RNA (mRNA) of TH regulated liver genes was also examined. TH deprivation down regulated spot 14 (S14) mRNA and showed no change in malic enzyme (ME) mRNA in both TR beta+/+ and TR beta-/- mice. In contrast treatment with L-T3 produced an increase in S14 and ME but no change in TR beta-/- mice. From these results, it can be concluded that regulation of HR and EE are independent of TR beta. With the exception of serum cholesterol concentration and liver ME mRNA accumulation, all other markers of TH action examined during TH deprivation exhibited the expected responses in the absence of TR beta. Thus, as previously shown for serum TSH, TR beta is not absolutely necessary for some changes typical of hypothyroidism to occur. In contrast, except for HR and EE, the full manifestation of TH-mediated action required the presence of TR beta.
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PMID:Thyroid hormone action on liver, heart, and energy expenditure in thyroid hormone receptor beta-deficient mice. 983 32

Insulin-like growth factor-binding protein-5 (rhIGFBP-5) is stored in bone and stimulates osteoblast cell proliferation in vitro. Bone formation is dependent on the number and activity of osteoblasts. We therefore evaluated the ability of recombinant human (rh) IGFBP-5 to increase osteoblast activity in vitro; both alkaline phosphatase (ALP) activity and osteocalcin levels showed a dose-dependent increase. In in vivo time-course studies, daily s.c. administration of 50 microg rhIGFBP-5/day/mouse significantly increased serum osteocalcin levels by day 7, and these levels were sustained through day 21. We further evaluated whether rhIGFBP-5 was as effective as IGF-I. Daily s.c. administration of rhIGFBP-5 (50 microg/day), IGF-I (13 microg/day), or IGF-I plus rhIGFBP-5 complex for 9 days increased serum osteocalcin levels by 58%, 65%, and 81% (P < 0.001 in all) and femoral bone extract ALP activity by 85% (P < 0.001), 29% (P < 0.05), and 13% (P = NS), respectively, and decreased carboxyl-terminal cross-linked telopeptide of type I collagen by 29% (P < 0.05), 20% (P = NS), and 12.5% (P = NS), respectively. One s.c. injection of rhIGFBP-5 (50 microg/mouse) increased serum osteocalcin and bone ALP activity by 21% (P < 0.05) and 27% (P < 0.02), respectively, after 5 days, but did not significantly increase serum IGF-I (1, 6, or 24 h/postinjection), suggesting that the effects of rhIGFBP-5 on bone are not mediated by increasing circulating IGF-I. Our data demonstrate that systemic administration of rhIGFBP-5, either alone or in combination with IGF-I, increases bone formation parameters in vivo.
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PMID:Recombinant human insulin-like growth factor-binding protein-5 stimulates bone formation parameters in vitro and in vivo. 1049 28

The mouse homozygous for a disruption of the klotho locus (KL-/- or klotho mouse) exhibited multiple pathological conditions resembling human aging. We observed osteopenia in KL-/- mice with a low bone turnover, in which the decrease in bone formation exceeded the decrease in bone resorption and resulted in net bone loss. This pathophysiology resembles closely that of senile osteoporosis in humans. Osteoblastic cells from KL-/- mice proliferated normally in vitro; however, they showed much lower alkaline phosphatase activity and mineralized matrix formation than those from control mice. Cultured osteoclastic cells from KL-/- mice had normal resorbing activity and survival rate, but the differentiation of osteoclastic cells from their precursors was significantly disturbed: in the co-culture of osteoblastic cells and osteoclast precursor cells, the formation of tartrate-resistant acid phosphatase-positive multinucleated osteoclastic cells was extremely poor only when osteoclast precursor cells originated from KL-/- mice independently of the origin of the osteoblastic cells. In addition, we found that osteoprotegerin a secreted factor which inhibits osteoclastogenesis, was up-regulated in KL-/- mice. We conclude that a defect in klotho gene expression leads to the independent impairment of osteoblast and osteoclast differentiation, which can be a cause of low-turnover osteoporosis.
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PMID:Cellular and molecular mechanism of low-turnover osteopenia in the klotho-deficient mouse. 1089 39


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