Progression alkaline phosphatase

Deming and Pardue studied the kinetics for the hydrolysis of p-nitrophenyl phosphate by the enzyme alkaline phosphatase. The progress of the reaction was monitored by measuring the absorbance due to p-nitrophenol, which is one of the products of the reaction. A plot of the rate of the reaction (with units of pmol mL s ) versus the volume, V, (in milliliters) of a serum calibration standard containing the enzyme yielded a straight line with the following equation... 

Once stem cells are committed to the osteoblast lineage, proliferating osteoprogenitors become preosteoblasts, cell growth declines, and there is a progressive expression of differentiation markers by osteoblasts (Stein et al. 1996). Osteoblastic differentiation is characterized by the sequential expression of alkaline phosphatase (ALP), an early marker of osteoblastic phenotype, followed by the synthesis and deposition of collagen type I, bone matrix proteins, and glycosaminoglycans and an increased expression of os-... 

A. Paget s disease is often asymptomatic and picked up on plain bone films. Patients with Paget s disease should have their serum calcium level determined to make sure that they are not hypercalcemic from excessive bone resorption, their serum alkaline phosphatase measured as a marker of new bone formation, a bone scan to determine whether other bones are involved, and a 24-hour urinary hy-droxyproUne measurement to assess bone resorption. The patient who has minimal involvement and is biochemically normal does not need pharmacological therapy. No studies indicate that early treatment slows progression in individuals with the more severe form of this disorder. 

The goal of treatment is to reduce bone pain and stabilize or prevent other problems such as progressive deformity, hearing loss, high-output cardiac failure, and immobilization hypercalcemia. Calcitonin and bisphosphonates are the first-line agents for this disease. Treatment failures may respond to plicamycin. Calcitonin is administered subcutaneously or intramuscularly in doses of 50-100 MRC (Medical Research Council) units every day or every other day. Nasal inhalation at 200-400 units per day is also effective. Higher or more frequent doses have been advocated when this initial regimen is ineffective. Improvement in bone pain and reduction in serum alkaline phosphatase and urine hydroxyproline levels require weeks to months. Often a patient who responds well initially loses the response to calcitonin. This refractoriness is not correlated with the development of antibodies. 

Figure 36.6. Snapshot of the Method creator of the Immusoft computer programme serving for the establishment of assay protocols. The figure shows on the right-hand side the various steps of the protocol developed for the assay of alkaline phosphatase (ALP), in which the functionalisation of the microchannels (coating and blocking steps) is directly integrated in the assay progress.

Martinez, J., and F. Azam. 1993. Periplasmic aminopeptidase and alkaline phosphatase activities in a marine bacterium Implications for substrate processing in the sea. Marine Ecology Progress Series 92 89-97. 

Alkaline phosphatase (ALP) is present in high concentrations in the cells lining the biliary tract and an ALP level exceeding 300 IU/L, together with a raised bilirubin as in the case of Mrs MW, is indicative of cholestasis. Jaundice becomes progressively more severe in unrelieved cholestasis. 

A transient, moderate, and reversible rise in leukocyte alkaline phosphatase, lactate dehydrogenase (LDH) and serum uric acid concentrations is usually observed in cancer patients receiving supportive treatment with GM-CSF or G-CSF. Serum LDH increased from 37 to 85% and there was a linear relation between increased leukocyte production and the rise in serum LDH (32). Increases in serum LDH activity should therefore not be interpreted as indicative of disease progression, unless LDH activity remains high after growth factor withdrawal. 

A physiologic phosphate concentration is required for bone mineralization. Lowering the concentration prevents mineralization, but raising it does not ensure precipitation because pyrophosphate is present to inhibit precipitation. The concentration of PPi in cartilage and bone is controlled by three enzymes, two on the outer surface of matrix vesicles (Fig. 9.5b). One is tissue-nonspecific alkaline phosphatase (TNAP), which decreases stromal pyrophosphate and the other is NTP-PPi hydrolase (also called plasma cell membrane glycoprotein-1), which increases it. The progressive ankylosis gene product (ANK protein) is expressed by osteoblasts to add to the pyrophosphate of the osteoid matrix from osteoblast cytosol. 

Seligmann s team (S8) first recognized a-chain in a disease which had been well known in the Middle East for some years as Arabian lymphoma of the small gut. This seems to have a genetic basis, the two Pakistanis I have seen possibly reflecting the travels of Alexander the Great. It often presents in the late teens as progressive, then intractable, malabsorption. Radiology reveals a stove-pipe small gut, whose whole wall becomes involved with plasmacytoma. Initially the tumor seems to be confined to the small gut, with normal secretory IgA in the rectum and in saliva, but later may spread locally, to tonsils, etc., and to bone marrow. The serum alkaline phosphatase develops an excess of intestinal... 

With the aid of photomicrographs of the L-phenylalanine-sensitive placental alkaline phosphatase, one can picture the placental villi in contact with the maternal circulation (H3) and so enriching it with alkaline phosphatase. In support of this view, we have demonstrated a progressive rise in pregnancy of heat-stable LPSAP with an optimum pH of 10.7. 

Extraskeletal calcification occurs in several conditions unrelated to demonstrable abnormalities of calcium metabolism, such as scleroderma, myositis ossificans, calcinosis universalis, calcinosis cutis, and local tissue damage in the kidney. These disorders are not usually associated with changes in serum alkaline phosphatase (B30). Elevated values have, however, been reported in paraplegic patients with ectopic bone formation (F23), and a positive correlation has been demonstrated between the activity of serum alkaline phosphatase and the progression of this disorder. Nicholas (N4) claimed that hyperphosphatasemia in such a situation may help to differentiate thrombophlebitis, septic arthritis, and cellulitis from ectopic bone formation. 

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