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)

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered at a dose of 1-60 micrograms/kg of body weight to 22 patients with transitional cell carcinoma before chemotherapy as part of a Phase I/II study. In all patients, a specific dose-dependent increase in the absolute neutrophil count (ANC) of 1.8-12 fold was seen. In addition, this augmentation in the ANC was accompanied by an increase in leukocyte alkaline phosphatase, a marker of secondary granule formation. In six of eight patients analyzed, an increase in bone marrow myeloid to erythroid cell ratio was seen. Day 14 peripheral blood cell derived colony forming unit granulocyte macrophage were also increased by day 6 of rhG-CSF treatment. Circulating levels of eosinophils and basophils were unchanged; however, a 10-fold increase in monocytes was observed in patients treated at the highest doses. There was also a small increase in CD3+ lymphocytes that was not dose dependent. Hemoglobin, hematocrit, and platelet count remained near baseline throughout the period of rhG-CSF administration. These findings demonstrate that rhG-CSF is a potent stimulus for normal neutrophil proliferation and maturation.
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PMID:Phase I study of granulocyte colony-stimulating factor in patients with transitional cell carcinoma of the urothelium. 245 63

We have previously shown that a factor termed neutrophil alkaline phosphatase-inducing factor (NAP-IF) has the capacity to induce neutrophil alkaline phosphatase (NAP) in postmitotic granulocytes (PMGs). This factor has characteristics similar to those of granulocyte colony-stimulating factor (G-CSF), suggesting that the two factors assayed by different methods may be attributable to an identical macromolecule. In a preliminary experiment, we showed that purified natural G-CSF (nG-CSF) could induce NAP in vitro in the presence of 10% (v/v) fetal calf serum (FCS). In this study, purified human nG-CSF and recombinant G-CSF (rG-CSF) induced NAP in granulocytes from both normal individuals and patients with chronic myelogenous leukemia in a dose-dependent fashion in serum-free and serum-containing culture conditions. The induction of NAP by G-CSF was detectable at 0.4 ng/ml and became maximal between 10 and 20 ng/ml. Anti-G-CSF serum incubated with either NAP-IF or rG-CSF inhibited induction of NAP. Morphological examinations revealed that granulocytes cultured with G-CSF were more mature than those cultured without G-CSF, indicating that G-CSF promoted maturation of granulocytes in parallel with NAP induction. These results indicate that NAP-IF in the cystic fluid of a human squamous cell carcinoma is identical to G-CSF and that induction of NAP by G-CSF is really a reflection of cell maturation promoted by G-CSF.
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PMID:Identification of neutrophil alkaline phosphatase-inducing factor in cystic fluid of a human squamous cell carcinoma as granulocyte colony-stimulating factor. 246 75

Congenital agranulocytosis is a disorder characterized by severe neutropenia and a profound deficiency of identifiable neutrophil progenitors in bone marrow. In an attempt to stimulate neutrophil production and thereby reduce the morbidity and mortality associated with this disease, we administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) in doses of 3 to 60 micrograms per kilogram of body weight per day to five patients with congenital agranulocytosis. In all five patients, an increase in the number of neutrophils was noted eight to nine days after the initiation of the effective dosage (the dose at which the neutrophil count reached 1000 cells per microliter or more and the bone marrow showed granulocyte maturation beyond the myelocyte stage). The absolute neutrophil counts rose from less than 100 to between 1300 and 9500 cells per microliter. Marrow aspirates obtained after 14 days at the effective dosage showed maturation to the mature neutrophil stage. The side effects that were observed were medullary pain, splenomegaly, and an elevation of levels of leukocyte alkaline phosphatase. All five patients have had sustained neutrophil counts of 1000 cells per microliter or more for 9 to 13 months while receiving subcutaneous maintenance therapy. Preexisting chronic infections have resolved clinically, and the number of new infectious episodes and the requirement for intravenous antibiotics have decreased. We conclude that treatment with rhG-CSF can lead to a large increase in the numbers of functional neutrophils in patients with congenital agranulocytosis.
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PMID:Effects of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with congenital agranulocytosis. 247 Oct 75

Seventeen patients with advanced malignancy were treated with recombinant human granulocyte colony stimulating factor rhG-CSF (KRN 8601) infused intravenously over a period of 30 minutes once daily at the dose level/25 micrograms, 50 micrograms, 100 micrograms, 200 micrograms, 400 micrograms, 800 micrograms/m2 for 14 consecutive days, and the effect was compared to the period without rhG-CSF treatment. The maximum numbers of peripheral leukocyte (granulocyte) showed a dose-related increase and the nadir of leukocyte counts escalated with shortening of the period. After stopping infusion, the neutrophil count dropped to the base line level within two or three days. RhG-CSF did not affect other components of peripheral blood such as monocyte, lymphocyte, eosinophil, and hemoglobin value and platelet counts. Transient bone pain occurred in two patients receiving a dose of 800 micrograms/m2. The biochemical changes detected were increased total alkaline phosphatase activity in serum, which appeared in parallel with the increase of neutrophil numbers, and less elevation of total uric acid values. We conclude that an optimal dose of rhG-CSF is 100 micrograms/m2 (average maximum peripheral granulocyte count, 10799/microliters; nadir granulocyte count, 3772/microliters; period of neutropenia, 2.6 days), and rhG-CSF is useful for acceleration of neutrophil recovery and prevention of infection from chemotherapy.
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PMID:[Effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) in patients receiving chemotherapy--phase I study]. 247 61

We studied the in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on white blood cell (WBC) count and neutrophil functions in nine patients with malignant lymphoma. The WBC count and absolute neutrophil count were rapidly increased without a nadir phase after chemotherapy. Neutrophil alkaline phosphatase (NAP) scores also markedly increased following chemotherapy in all patients. Phagocytosis of India ink and nitroblue tetrazolium (NBT) reduction were revealed tend to be increased, but not exceeded significantly to normal range. RhG-CSF repaired neutrophil function in patients with decreasing that. Thus, rhG-CSF may be useful for prevention and treatment of infection after chemotherapy.
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PMID:[Effect of recombinant human granulocyte colony-stimulating factor on white blood cell count and neutrophil functions in patients with malignant lymphoma]. 248 Apr 62

A 6-year-old girl with cerebral palsy developed conscious disturbance and generalized convulsion after one-hour hot herb drug bath. Physical examination on admission revealed rectal temperature 41 degrees C, hot skin, respiration 46/min, regular heart beat 98/min, BP 130/60 mmHg, Glascow coma scale 4 (E2M1V1), soft and flat abdomen, no hepatosplenomegaly, no skin rash, no focal neurological sign, increased generalized muscle ton. Laboratory data showed CBC: WBC 20400 cumm (Neutrophils 31%, Lymphocytes 69%), Hb 11.6gm%, ESR 11 mm/hr, arterial blood gas: PH 7.077, PO2 43mmHg, PCO2 57.1mmHg, HCO3- 16 mEq/L, BE-11.5mEq/L, serum sodium 143 mEq./L, potassium 5.2 mEq/L, chloride 101 mEq/L, free calcium ion 3.8mg%, GOT 63IU/L, GPT 263 IU/L, amylase 193 IU/L, alkaline phosphatase 388 IU/L, LDH 1245 IU/L, CPK 677 IU/L, total bilirubin 0.8 mg/dl, direct type 0.1 mg/dl, BUN 18 mg/dl, Glucose 35 mg/dl. Urinalysis revealed proteinuria( ) trace hematuria and pyuria, but no cast. Lumbar puncture is within normal limits. Bacteriology including blood and CSF are normal. Multiple organ failure was noted at that time. Intensive cooling methods were performed including central and peripheral cooling. We used luminal and valium to control the seizure. Condition didn't improve. Afterwards cardiopulmonary arrest developed. Patient expired 8 hours after admission despite of resuscitation. Heat stroke in infancy and childhood is different from that in adulthood. The predisposing factors are high ambient temperature, dehydration, very young baby, sweat gland dysfunction, or ectodermal dysplasia. Definition of heat stroke includes 1) rectal temperature above 41 degrees C, 2) behavioral change, 3) warm skin, wet or dry.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Status epilepticus induced by prolonged immersion in hot herb bath: report of one case]. 263 19

The mouse granular convoluted tubules of submandibular gland of laboratory mouse are releasing a range of biologically active peptides (renin, neural growth factor and others) into both the saliva and blood circulation, the males producing it in a larger extent than females. Recently, several from respective peptides were identified to be endogenous ones and brain-related. The present work was aimed to utilise submandibular gland/SMG auto- and isotransplants regenerating in murine brain as a possibly local source of peptides. Experimentally, the newborn and juvenile matured white A breeded mice of both sexes were used. Glandular grafts were grafted into brain parenchyma or CSF spaces. Laboratory animals have then been perished during the first 6 weeks after transplantation, and the transplants so acquired evaluated as serial frontal sections embedded in paraffin and H.E. stained by light microscopy. Also cryocate sections were incubated in order to detect the presence of alkaline phosphatase (AP) and succinic dehydrogenase/(SDH). It was stated experimentally that both mentioned SMG grafts underwent the survival and development intracerebrally. Some first regressive changes were gradually replaced by glandular proliferation and lobular neomorphogenesis having been more pronounced in osotransplants. The proliferative period was characterized by cellular mitoses, multiplication of duct-like and terminal tubulous structures of newly formed glandular lobules. Partially, the isotransplants display the transformation of proliferation stage into that of cellular cytodifferentiation followed by gradual appearance of striated ducts, acini and even granular convoluted tubules on the 5th week after transplantation. Also the reoccurrence of enzyme activities in the transplant parenchyma after their initially total disappearance is testifying of both proliferation and cytodifferentiation developed gradually. During the first days of implantation, the revascularization of grafts occurs, those being high in AP endothelial activity of vessels newly formed. This is to conclude that higher proliferative intensity of isotransplants and their exclusive cytodifferentiation demonstrate that an undifferentiated murine SMG which can develop itself ontogenetically is more effective graft than a SMG differentiated fully. On the next stage, the development of glandular grafts will be studied with more delay after transplantations. Also the enzyme implementation of new parenchymatous components is to be elucidated. Further experimentation is planified as to influencing intracerebral SMG graft development with administration of hormones and isoproterenol to laboratory animals.
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PMID:[Regeneration of auto- and isografts of submandibular glands in the brain of laboratory mice. I. Morphologic evaluation of the healed graft using light microscopy]. 264 Mar 57

The activity of human osteoblast-like cells cultured in vitro is regulated by a number of factors, which include systemic hormones as well as agents that can be produced locally within bone. Several cytokines and growth factors have been demonstrated to be produced by osteoblasts themselves, and this includes granulocyte-macrophage colony-stimulating factor (GM-CSF). In this report we show that recombinant human GM-CSF (rhGM-CSF) modulates the activities of osteoblast-like cells derived from human trabecular bone in vitro. rhGM-CSF stimulated the proliferation of the cultured human osteoblast-like cells, but antagonised the induction by 1,25(OH)2D3 of osteocalcin synthesis and alkaline phosphatase activity, two characteristic products of osteoblasts. rhGM-CSF however, had no appreciable effect on the production of prostaglandin E2, or on the plasminogen activator activity associated with human osteoblast-like cells. These results are the first report of which we are aware of an apparently direct action of GM-CSF on cells of the osteoblast phenotype. These studies indicate that GM-CSF represents another haematological factor that can potentially exert regulatory actions on human osteoblast-like cells. GM-CSF may therefore be a potential paracrine/autocrine regulator of osteoblast activity.
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PMID:The effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on human osteoblast-like cells. 265 92

We examined the in vitro effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophil anomalies in 20 patients with myelodysplastic syndromes (MDS) and eight patients with chronic myelogenous leukemia (CML). Neutrophil alkaline phosphatase (NAP) activity was determined in nine MDS patients and eight CML patients by a scoring method. NAP scores were decreased in six of the nine patients with MDS and in all of the patients with CML. In all patients with these diseases, NAP scores increased by incubating the blood with rhG-CSF. An increase in NAP scores by rhG-CSF was observed even at a concentration of 1 U/mL in patients with MDS but was observed only at higher concentrations (1,000 to 10,000 U/mL) in patients with CML. Significant increases in NAP scores occurred at 12 hours' incubation in patients with MDS, whereas the increase was more gradual in patients with CML. This time course difference was thought to be due mainly to the difference in cell populations of circulating myeloid cells between MDS patients and CML patients. Induction of NAP activity by rhG-CSF in patients with both these diseases was suppressed by the addition of inhibitors of RNA or protein synthesis. Neutrophil superoxide anion (O2-) production induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was determined in the other 11 patients with MDS. This neutrophil function was decreased in seven of the 11 patients with MDS, normal in two patients, and increased in two patients. Preincubation with rhG-CSF caused a significant increase in fMLP-induced O2- production in nine of the 11 patients with MDS. rhG-CSF enhanced this neutrophil function in a time- and dose-dependent manner, and maximal stimulation was observed at 2,000 to 4,000 U/mL of rhG-CSF and at five to ten minutes' incubation. The present results show that rhG-CSF is able to repair at least in part the neutrophil anomalies in these patients, and our data, especially for patients with MDS, suggest the clinical usefulness of rhG-CSF for this preleukemic disorder.
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PMID:Recombinant human granulocyte colony-stimulating factor repairs the abnormalities of neutrophils in patients with myelodysplastic syndromes and chronic myelogenous leukemia. 303 12

The role of osteoblasts in inducing the proliferation and differentiation of bone marrow cells was examined. Conditioned medium obtained from mouse osteoblastic cell (MC3T3-E1) cultures stimulated colony formation of mouse bone marrow cells (CSF) and differentiation of mouse myeloid leukemia cells (M1) into macrophage-like cells (D-factor). The CSF activity increased time dependently in parallel with the increase of alkaline phosphatase activity during the culturing of the MC3T3-E1 cells. The activity of the D-factor attained a maximum on days 12 - 15 and decreased thereafter. Both the CSF and the D-factor were eluted in a range of 25,000 to 67,000 daltons on gel filtration. The fraction containing both factors exhibited bone-resorbing activity. These results suggest that osteoblasts are involved in bone resorption at least in part by enhancing the proliferation and differentiation of osteoclast progenitors.
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PMID:Synthesis of colony-stimulating factor (CSF) and differentiation-inducing factor (D-factor) by osteoblastic cells, clone MC3T3-E1. 348 50


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