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)

Osteosarcomas were produced by the intratibial inoculation of New Zealand black rats with Moloney sarcoma virus (MSV) at 1 day and 4 days of age. Radiographic evidence of osteosarcoma development was first demonstrated at 10 to 15 days postinoculation in both groups. Subsequent radiographic and light and electron microscopic evaluation of tumor-bearing rats demonstrated that osteosarcomas in rats inoculated at Day 4 of age were more osteoproliferative osteosarcomas than those in rats inoculated on Day 1. Rats inoculated at 4 days of age lived longer, had more slowly growing osteosarcomas, and developed a consistent tumor-associated cachexia compared to tumor-bearing rats inoculated at Day 1. Both groups of rats had a 93% metastasis rate involving either sublumbar lymph nodes, lungs, or both. Tumor-bearing rats inoculated at 4 days of age had consistent elevations in both urinary hydroxyproline excretion (HOP/CR) and serum alkaline phosphatase levels, and in serum calcium levels at some time points. The high tumor incidence after a short latent period and the morphologic and biochemical similarities between the MSV-induced murine osteosarcoma and the osteosarcoma in human beings makes this discrete tumor and a valuable animal model for the evaluation of new therapeutic regimens.
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PMID:Virus-induced animal model of osteosarcoma in the rat: Morphologic and biochemical studies. 18 16

Improvement in drug response and reduction of toxicity were observed after continuous intrahepatic arterial infusion of mytomycin-C (MMC) and 5-fluorouracil (5-FU) in 15 of 26 patients with primary or metastatic carcinoma of the liver. Serum bilirubin values of 10 mg/100 ml absence of ascites, extreme cachexia and impending hepatic failure were used as the criteria for admission of these patients into the study. The patients were given MMC in a dose of 0.08 mg/kg on day 1,5-FU in a dose of 8-10 mg/kg on days 2-5, and MMC on day 6. This schedule was reinitiated on days 8 and 15 for total mean duration of 18 days. Maintenance therapy was carried out by the administration of these drugs at induction dosage alternated each week as a single 24 hourly intravenous infusion. Objective response to combination therapy was defined as decrease of at least 50% in the liver size and in the abnormal levels of serum alkaline phosphatase and glutamic oxaloacetic transaminase (SGOT), and near normal levels of serum bilirubin for a minimum period of 2 months. The duration of objective response ranged from 3-16 months with a median of 8.2 months. The median survival time for the responders was 7.2 months for patients with primary carcinoma and 9.4 months for patients with metastatic carcinoma of the liver as compared to 2 months for patients who failed to respond to the treatment. Five out of 12 patients who were refractory to MMC or 5-FU by intravenous infusion responded to the present combination drug therapy. Of four patients who died during induction therapy, three had liver failure and the fourth suffered pulmonary embolism. These studies provide evidence that combination therapy with MMC and 5-FU increases the survival time of patients with hepatic cancer, presumably due to the synergistic action of these drugs which permits the use of a low dosage schedule and has less toxic effects.
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PMID:Intrahepatic arterial infusion of combination of mitomycin-C and 5-fluorouracil in treatment of primary and metastatic liver carcinoma. 19 31

The chemotherapeutically effective 5:1 combination N1-(4,5-dimethyl-2-oxazolyl)-sulfanilamide (sulfamoxole) and 2,4-diamino-5-(3,4,5-trimethoxy-benzyl)-pyrimidine (trimethoprim) (CN 3123, Nevin, Supristol) was investigated to determine any evidence of toxicological potentiation or new toxic signs. It was found that CN 3123 had a very low acute toxicity when administered orally to mice, rats and dogs (oral LD50: mouse greater than 12 000 mg/kg; rat greater than 14 000 mg/kg; dog greater than 1000 mg/kg body weight). The combination was also tolerated by rats and dogs in repeated doses administered over a period of 4 or 26 weeks, that greatly exceeded the therapeutic dose. The only change observed occurred in the thyroid, which in all doses administered exhibited a dose-related increase in weight accompanied by histological changes indicating an activation of thyroid function and a hypersecretion of basophilic thyrotropic cells in the anterior lobe of the pituitary. Six weeks after discontinuation of treatment this condition showed a tendency to reversibility or had already returned to normal. In dogs there was a dose-related increase in iodine uptake by the thyroid and a decrease in serum thyroxine over a period of 6 months under the highest dosage of CN 3123 administered. Whereas the thyroid changes observed under the combination could be reproduced with sulfamoxole, no effect on thyroid weight was observed in rats and dogs in the subacute toxicity phase of a comparative investigation with trimethoprim. Moreover, trimethoprim did not increase the effect of sulfamoxole on the thyroid gland. The effect of sulfamoxole on the thyroid is discussed in detail with a review of the literature. It can be characterized as species-specific for sulfonamides in mice, rats, rabbits and dogs but not in monkeys or in man and appears to be caused by the inhibition of the organic binding of iodine in the thyroid, whereby the predisposing factors must vary considerably from species to species. The thyroid hypertrophy observed is due to the activation of the regulatory cycle via the anterior lobe of the pituitary. The following systemic changes occurred after 600 mg CN 3123/kg, a lethal-toxic dosage and the highest administered in the study: reduced body weight, decreased food consumption leading to cachexia, slightly increased SGPT and alkaline phosphatase, slight thrombocyte depression, enlargement and increased fatty degeneration of the liver, occurrence of necrotic areas in the liver, hemosiderin accumulation in Kupffer's cells, and an increase of reticular cells in the spleen. The acute toxicity of CN 3123 and all major functional and histological changes under repeated administration were due exclusively to sulfamoxole. The combination sulfamoxole/trimethoprim gives no indication of toxicological potentiation or new toxic signs.
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PMID:[Toxicological investigations of the combination sulfamoxole/trimethoprim, a new broad-spectrum chemotherapeutic (author's transl)]. 94 24

A transplantable ascites-forming osteosarcoma (J. H. 1-AOS) derived from the 35th generation of spontaneous osteosarcoma, J. H. 1-OS, grown in Fischer 344 syngeneic rats was established. Tumorigenicity, histochemical and ultrastructural characteristics were investigated. Rats carrying the ascites form osteosarcoma died of cachexia about 15 days after transplantation, 1.5-2.5 x 10(6) cells/ml of tumor cells generally being involved in the ascites and tumor nodules formed in the mesentery. After inoculation into the back subcutaneous space, tumor growth was very rapid. Small round cells were detected in the Giemsa stain smear, and although osteoid formation was histologically lacking, cell surface alkaline phosphatase activity was noted both light and electron microscopically. Polyacrylamide gel electrophoresis demonstrated that alkaline phosphatase (Al-p) extracted from this tumor was consistent with Al-p from rat fetal calvaria. Thus maintenance of osteogenic potential is suggested for these ascites osteosarcoma cells, indicating their usefulness for further studies of biological behaviors of this tumor type.
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PMID:[Establishment and characterization of an ascites-forming rat osteosarcoma cell line]. 154 42

Goats infected with caprine arthritis-encephalitis virus (CAEV) show chronic arthritis and cachexia, which are progressive in nature. The immunopathogenic mechanisms responsible for these progressive clinical symptoms have not been fully elucidated. Various haematological and immunological parameters were evaluated in experimentally-infected goats showing typical signs of CAEV-induced disease. Infected goats showed recurrent lymphocytosis that may be due to constant presentation of antigen by infected cells of a monocyte/macrophage lineage. The serum alkaline phosphatase and gamma-glutamyl transferase concentrations were elevated in infected goats, a characteristic of hepatic and bone disorders. All other serum chemistry parameters were similar between infected and control goats. Importantly, the serum tumour necrosis factor-alpha (TNF-alpha) levels were higher in infected goats. The cachexia seen in infected goats may be at least partly due to altered metabolism as a result of prolonged elevation of serum TNF-alpha levels. Depressed natural killer cell activity was observed in infected goats and may contribute towards the establishment of a persistent infection with CAEV.
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PMID:Pathogenic mechanisms of caprine arthritis-encephalitis virus. 770 86

A fatal case of hepatic actinomycosis with portal vein thrombosis is reported. The diagnosis of actinomycosis was delayed because of its rarity in Taiwan. This 63-year-old man was admitted due to body weight loss and poor appetite. No fever was noted before admission. Liver biochemical test showed a decreased serum albumin level with elevated serum levels of globulin and alkaline phosphatase. He was not a hepatitis B carrier and his serum level of alfafetoprotein was within normal range. Image studies (abdominal sonography and computed tomography) showed a hepatic mass over the medial segment of the left lobe with involvement of right lobe of the liver. Main portal vein thrombosis was also seen. Because of profound cachexia, he died of aspiration pneumonia and disseminated intravascular coagulation on the 11th day after admission. An autopsy revealed hepatic actinomycosis. High index of suspicion for early diagnosis and treatment is emphasized.
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PMID:Hepatic actinomycosis with portal vein thrombosis mimicking hepatocellular carcinoma: a case report. 839 99

A material of Mr 24,000 has been isolated from a cachexia-inducing mouse tumor (MAC16) and shown to initiate protein degradation in isolated gastrocnemius muscle. Biological activity was destroyed by preincubation with peptide N-glycosidase F (PNGase F) and endo-alpha-N-acetylgalactosaminidase (O-glycosidase) but not by neuraminidase or trypsin. Antibody reactivity was destroyed by treatment with periodate, indicating carbohydrate moieties to be the antigenic determinants. Antigenic activity was also reduced by treatment with PNGase F and O-glycosidase and was completely destroyed by treatment with chondroitinase ABC but was unaffected by treatment with either trypsin or chymotrypsin, confirming that the N- and O-linked sulfated oligosaccharide chains were both the antigenic and biological determinants. Biosynthetic labeling of MAC16 cells using a combination of [35S]sulfate and [6-3H]GlcN gave a single component of Mr 24,000 containing both radiolabels. Similar material could not be isolated from a cell line (MAC13) originating from a tumor that does not cause cachexia in vivo. Digestion of 3H/35S material with PNGase F produced two fragments of Mr 14,000 and 10,000 containing both radiolabels, and digestion with O-glycosidase produced three fragments of Mr 14,000, 6,000, and 4, 000, the first two contained both radiolabels and the third contained only 3H. Digestion of the fragment of Mr 14,000 released by PNGase F with O-glycosidase also gave fragments of Mr 6,000 and 4, 000. The products from both digestions were acidic as determined by anion exchange chromatography on DEAE-cellulose. The negative charge on the fragment of Mr 4,000 was removed by treatment with alkaline phosphatase. This suggests that the charge originated from phosphate residues, and this has been confirmed by biosynthetic labeling of MAC16 cells with [32P]orthophosphate, where radiolabel was incorporated into material of Mr 24,000 and into the fragment of Mr 4,000 after treatment with O-glycosidase. To determine the size of the polypeptide core MAC16 cells were biosynthetically labeled with L-[2,5-3H]His which after chemical deglycosylation produced a major component of Mr 4,000. These results suggest a model for the Mr 24, 000 material consisting of a central polypeptide chain of Mr 4,000 and with phosphate residues that may be attached to the polypeptide or a short oligosaccharide chain containing GlcN, one O-linked sulfated oligosaccharide chain containing GlcN, and of Mr 6,000 and one N-linked sulfated oligosaccharide chain of Mr 10,000 also containing GlcN. Neither chain was cleaved into disaccharides with chondroitinase ABC, suggesting that the material is a sulfated glycoprotein.
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PMID:Structural analysis of a tumor-produced sulfated glycoprotein capable of initiating muscle protein degradation. 913 70

Over 23 months, zinc toxicosis was diagnosed in 35 baboons aged 5-12 months in one galvanized metal and concrete cage complex with conditions that led to excessive exposure to environmental zinc. Clinical signs included reduced pigmentation of hair, skin, and mucous membranes (whiteness), alopecia, dehydration, emaciation, cachexia, dermatitis, diarrhea and, in six cases, severe gangrenous dermatitis of extremities. The syndrome was characterized by pancytopenia, elevated zinc and low copper serum concentrations, low vitamin D and bone-specific alkaline phosphatase levels, and atypical myelomonocytic proliferation of bone marrow. This syndrome emphasizes the importance of proper husbandry and cage design and indicates the potential of infant baboons as a model to study the effects of excessive zinc on development. This is the first report describing the epidemiologic and clinical presentation of zinc toxicosis in infant baboons in captivity.
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PMID:White monkey syndrome in infant baboons (Papio species). 1527 Oct 69

A 42-year-old woman presented with a rapidly growing tumor of the breast accompanied by anemia (7.4 g/dL), hypoalbuminemia (1.6 g/dL), and increased alkaline phosphatase (256 U/L). Magnetic resonance imaging of the breast demonstrated a heterogeneous mass composed of verrucous solid components with hemorrhagic areas. There was no evidence of cachexia, and the metastatic workup was negative. Final pathology revealed a 22-cm malignant phyllodes tumor. Hypoalbuminemia and alkaline phosphatase quickly resolved after surgical excision without any further treatment.
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PMID:Resolution of hypoalbuminemia after excision of malignant phyllodes tumor. 1723 67

In 2005 and 2006 an outbreak of disease associated with border disease virus (BDV) infection caused high mortality in the Pyrenean chamois (Rupicapra pyrenaica) in the Catalan Pyrenees (NE Spain). The aim of this study was to determine values for different haematological and serum biochemical analytes in 32 free-ranging Pyrenean chamois affected by the disease and to compare them with those obtained from healthy chamois. In the affected chamois red blood cell counts, haemoglobin concentrations, packed cell volumes, mean corpuscular volumes and lymphocyte counts were all lower, while the neutrophil and platelet counts were higher. Glucose, lactate, triglycerides, creatinine, total protein concentrations and alkaline phosphatase activity were also lower, in contrast to the concentrations of total bilirubin, urea and aspartate aminotransferase activity, which were higher. Most of the observed changes could be associated with cachexia and inflammation in the affected chamois. Lymphopenia could be directly related to the BDV, which would lead to immunosuppression and explain the high rate of secondary infection observed in these animals.
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PMID:Haematology and serum chemistry of Pyrenean chamois (Rupicapra pyrenaica) naturally infected with a border disease virus. 2065 9


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