A rapid automated screening technique for the detection of placental-like alkaline phosphatase in malignant disease.

An automated heat-stability procedure at 65 degrees C for the detection of heat-stable placental and placental-like alkaline phosphatase is described. Placental-like enzymes were found in the serum of three patients suffering from malignant disease and one of these is described in detail.

Serum alkaline phosphatase, nucleotide pyrophosphatase, 5'-nucleotide and lipoprotein-X in cholestasis.

The nature of the stationary band of alkaline phosphatase, which occurs on starch gel electrophoresis of sera from patients with biliary obstruction, has been examined. Stationary alkaline phosphatase was eluted from Sepharose 4-B gel close to the void volume and together with the plasma membrane enzymes, nucleotide pyrophosphatase and 5'-nucleotidase, and with lipoprotein-X. Electron microscopy of concentrates of stationary alkaline phosphatase, prepared by ultracentrifugation and gel filtration, showed large (0.3--1 mum diameter) and small structures (30-70 nm diameter) by negative staining. The activity of the stationary alkaline phosphatase was associated in fixed sections with particles of about 10 nm X 40 nm resembling those of lipoprotein-X. It is suggested that the stationary alkaline phosphatase does not move into starch gel during electrophoresis because it is particulate. In agar electrophoresis the alkaline phosphatase which was stationary on starch gel moved towards the cathode with lipoprotein-X.

The incidence and likely origins of serum particulate alkaline phosphatase and lipoprotein-X in liver disease.

Both serum particulate alkaline phosphatase and serum lipoprotein-X have been proposed as diagnostic markers for obstructive liver diseases. In this study their diagnostic efficiencies have been compared with other biochemical indicators of liver function and the relative incidence of these two markers has been determined in 241 patients with well defined liver disease. Although these markers appeared together most frequently in obstructive liver disease they were both present in some patients with liver disorders where obstruction was unlikely. One marker was present, independently of the other in 35% of the patients studied, mainly those without apparent cholestasis. The reasons for this are discussed in terms of the likely origins of the two markers and the probability that serum particulate alkaline phosphatase exists in two forms, as part of a multienzyme plasma membrane complex and as soluble liver enzyme associated with lipoprotein-X.

Evidence for the hormonal regulation of the multimolecular forms of serum alkaline phosphatase.

PIP: The relationship between serum alkaline phosphatase (AP) activity and hormonal status was investigated in normally menstruating women. oral contraceptive (OC) users, and in women attending an infertility clinic and in early and late pregnancy. Reliable measurement of small differences in serum AP is now possible as a result of improvements in faractionation, sample handling techniques, and precision in AP assays. The centrifugal analyzer method used in these studies gives a within-batch precision of 0.4% compared to the 4-5% precision obtained with eaarlier methods. The maximun divergence in levels of circulating AP was noted in the 30-35year age group, which corresponds to the peak 24 hour urinary excretion of estrogen between days 10-20 of the menstrual cycle. Only limited changes of liver-bone AP were demonstrated in the luteal and menstrual phases of the normal cycle, although a marked increase in intestinal AP was noted during menses. Serum AP increased during menses in OC users. The removal of suppression on AP produces an increase during days 21-27. Among women attending an infertility clinic, those with lower hormone levels had a wider range of serum AP activity and a greater incidence of intestinal AP. The finding that ptients with progesterone levels under 7.5 nmol/1 with normal levels of estradiol has raised serum AP levels suggests that progesterone may modulate the estrogenic effect on serum AP levels. Finally, an inverse relationship was found between intestinal AP and levels of estradiol and progesterone in different phases of the menstrual cycle and in early and late pregnancy. These results suggest that small or large increases in estrogen increase pinocytosis, which reduces the level of the circulating glycoprotein AP by cell binding.^ieng

Amniotic fluid alkaline phosphatase, gamma-glutamyltransferase, and 5'-nucleotidase activity from 13 to 40 weeks' gestation, and alkaline phosphatase as an index of fetal lung maturity.

Reference ranges for amniotic fluid alkaline phosphatase, gamma-glutamyltransferase, and 5-nucleotidase are described from 13 to 40 weeks' gestation. Gamma-glutamyltransferase and 5-nucleotidase activities peak early in the second trimester and then decrease to low values. Alkaline phosphatase shows a similar pattern of activity from 13 to 29 weeks' gestation, but thereafter activity increases to term; this late increase is mainly related to the heat-labile particulate form of alkaline phosphatase. Total and heat-labile alkaline phosphatase alone or expressed as a ratio with gamma-glutamyltransferase can be used with or as an alternative to lecithin/sphingomyelin ratios in the investigation of fetal lung maturity. A total alkaline phosphatase activity of 0.36 mukat/L and an alkaline phosphatase/gamma-glutamyltransferase ratio greater than 2 indicate pulmonary maturity.

Factors affecting the ability of dental cements to alter the pH of lactic acid solutions.

Two related studies have been carried out to determine the effect of (a) powder:liquid ratio and (b) relative amounts of cement on the extent of buffering of a lactic acid storage solution using zinc polycarboxylate and glass-ionomer cements (both water-activated). The effect of varying the powder:liquid ratio was found to be slight and not statistically significant. On the other hand, increasing the numbers of specimens in a given volume of storage solution was found to have a significant influence on the final pH (at the 0.0005 level of significance). The fact that powder:liquid ratio did not affect the final pH led to the conclusion that attack occurs mainly at the matrix of these cements, confirming previous findings about the acid erosion process. The finding that increasing the relative amount of cement to acid storage solution strongly influenced pH suggested that, under clinical conditions, buffering would be important. When five specimens were used, the final pH corresponded to that of arrested caries, from which it was concluded that these cements have the ability to be cariostatic in vivo.

The value of 6-phosphogluconate dehydrogenase (6-PGDH) activity as a marker of tumour cellularity and prognostic indicator in primary breast cancer.

The value of 6-phosphogluconate dehydrogenase (6-PGDH) activity as a cytosolic marker of tumour cellularity has been assessed, together with its use as a prognostic indicator for primary breast cancer in 87 patients over 4 years. 6-PGDH activity shows a good correlation with histologically-assessed tumour cellularity in a sample of 114 patients (correlation coefficient = 0.83). Patients whose primary breast tumour had a high 6-PGDH activity showed poor relapse-free survival times when compared to those with low 6-PGDH activities (Log Rank chi 2 = 6.87, P less than 0.01). This compared with a Log Rank chi 2 of 2.22, P less than 0.20 for oestrogen positive and negative patients. These results suggest that 6-PGDH activity is a better prognostic indicator in primary breast cancer than oestrogen receptor status.

Relative importance of estrogen and progesterone receptor assays as prognostic indicators in primary breast cancer: a short-term study.

This short-term study of the relative importance of estrogen and progesterone receptors shows that progesterone receptor correlates better than estrogen receptor with tumor recurrence regardless of lymph-node status. Life-table analysis has effectively identified only two groups of patients that may be classified by progesterone receptor status alone. Progesterone-receptor negativity correlated well with tumors of histological Grade III; estrogen-receptor positivity correlated with Grade I and II tumors. The earlier recurrence of Grade III breast tumors may explain why progesterone receptor is a better prognostic indicator than estrogen receptor in short-term studies.