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Biomedical subjects

A F Smith

Publications and source records attributed to A F Smith.

At least 145 records · Page 8Linked to original sources
PubMed1981

High-molecular-mass alkaline phosphatase in serum and bile: physical properties and relationship with other high-molecular-mass enzymes.

High-molecular-mass alkaline phosphatase has similar properties in serum and bile. It is of sufficiently large size to be excluded by Sepharose 6B and carries a high negative charge at alkaline pH, largely accounted for by the presence of sialic acid residues. It is slightly more heat labile than the lower-molecular-mass liver isoenzyme. Other enzymes originating from the hepatocyte plasma membrane are present as similar high-molecular-mass forms in normal bile, and in both bile and serum from patients with liver disease. The activities of these relatively large enzymic forms in serum were correlated with one another and we show they are converted similarly to lower-molecular-mass forms by solubilization with detergents. However, they carry slightly different net charges, thereby ruling out the possibility that they all consisted of a single homogeneous multi-enzyme complex. These findings are discussed in the light of two current hypotheses that the high-molecular-mass enzymes represent (a) membrane fragments released into the circulation in liver disease or (b) low-molecular-mass enzymes that aggregate, after release, with the lipid and protein in the circulation.

Alkaline Phosphatase↗
PubMed1981

High-molecular-mass alkaline phosphatase in serum and bile: nature and relationship with lipoprotein-X.

Using immunoelectrophoresis and other techniques, we have demonstrated an association between lipoprotein-X and (a) alkaline phosphatase and (b) other enzymes originating from the hepatocyte membrane, namely gamma-glutamyltransferase and leucine aminopeptidase. The high-molecular-mass forms of these enzymes, in both serum and bile, were precipitated by lipoprotein-X antiserum but not by antisera to other plasma proteins. The activity of high-molecular-mass alkaline phosphatase in serum was positively correlated with lipoprotein-X and with lipoprotein-X-associated alkaline phosphatase, both assessed semi-quantitatively. On the other hand, many sera possessed high activities of high-molecular-mass alkaline phosphatase but no detectable lipoprotein-X. Incubation of serum with conjugated bile salts and with synthetic detergents, at concentrations which did not dissociate the high-molecular-mass enzymes, caused parallel alterations in the electrophoretic mobility of serum lipoprotein-X and its associated enzyme activity. Incubation of normal dialyzed hepatic bile with normal, lipoprotein-X-negative serum produced an alteration in electrophoretic mobility of biliary lipoprotein and its associated enzyme activity from anodal to cathodal in agar gel. Digestion with papain had a variable effect on the different enzymes in the complex, without affecting the lipoprotein moiety. Leucine aminopeptidase was removed most readily from the complex to give the low-molecular-mass form present in normal serum; gamma-glutamyltransferase dissociated somewhat less readily, and alkaline phosphatase was completely resistant to dissociation from the complex. These results are discussed in the light of current knowledge, and a hypothesis is proposed for the nature of the high-molecular-mass enzymes in serum and bile.

Alkaline Phosphatase↗
PubMed1980

Preoperative assessment and staging of breast cancer: preliminary communication.

A prospective study has been carried out in 172 women to determine the sensitivity of methods to detect occult metastatic disease in the skeleton and liver. With the exception of bone scintiscans, the results of these tests bore little relationship to recurrence rates. On the other hand, knowledge of the histopathology of the lower axillary (pectoral) lymph nodes is of value in this respect.A follow-up study is also reported which confirms the importance of accurate measurements of the primary tumour clinical node status and oestrogen receptor contact of the tumour in defining prognostic groups. Elastosis (estimated in 165 tumours) did not prove to be a useful prognostic index.

Bone Neoplasms↗
PubMed1980

Alkaline phosphatase of high and low molecular mass in human serum and bile: a comparative study of kinetic properties.

We studied the kinetic properties of high- and low-molecular-mass forms of alkaline phosphatase purified from serum and bile, to clarify their interrelationships. They were found to share virtually identical kinetic properties, and to obey the same general kinetics as the liver-derived isoenzyme from serum and the low-molecular-mass isoenzyme from bile with regard to optimum conditions of assay, activation by magnesium ions, inhibition by L-homoarginine, inhibition by nickel and zinc ions, and inactivation by urea. Most of the characteristics such as Km (at low magnesium ion concentrations), Ki for L-homoarginine, and half-life for urea inactivation, were closely similar for low- and high-molecular-mass alkaline phosphatase. We conclude that these forms of alkaline phosphatase in plasma and bile are closely related. We discuss the possible nature of this relationship.

Alkaline Phosphatase↗
PubMed1979

An ion-exchange assay for high molecular weight alkaline phosphatase.

An ion-exchange method for the measurement of a high molecular weight form of alkaline phosphatase in serum is described. The method is simple, rapid, precise and suitable for processing small batches of samples. Other forms of alkaline phosphatase commonly encountered in serum do not interfere. The correlation between results obtained by this method and those obtained by Sephadex 6B chromatography is discussed. Electrophoretic methods of measurement were also investigated but were found to be both imprecise and inaccurate.

Alkaline Phosphatase↗
PubMed1979

High molecular weight alkaline phosphatase: a clinical study.

High molecular weight alkaline phosphatase activities have been measured in the sera of 72 patients with a variety of forms of liver disease, 14 patients with bone disease and 8 healthy volunteers. These measurements have been compared with measurements of other indices of hepatic function in order to establish the place of this enzyme in the diagnosis of liver disease. High molecular weight alkaline phosphatase proved to be a sensitive and specific tests for detecting liver disease, particularly obstructive liver disease. It was better than all the other liver function tests in distinguishing liver metastases from other hepatobiliary diseases. It may therefore prove especially useful in the early detection of liver metastases.

Adult↗
PubMed1979

Glycosylated haemoglobin concentrations in newly diagnosed diabetics before and during treatment.

Concentrations of total glycosylated haemoglobins (Hb A1) were measured in 40 diabetics at diagnosis and at monthly intervals after treatment with chlorpropamide, insulin, or diet alone was begun. The mean Hb A1 concentration at presentation in 16 patients treated with chlorpropamide was significantly higher than that in 12 patients treated with insulin, and the duration of glycaemic symptoms was much longer in the chlorpropamide-treated group. In contrast, the mean plasma glucose concentration was similar in both groups. The mean concentrations of Hb A1 and plasma glucose at diagnosis in the 12 patients treated by diet alone were lower than those in the other two groups, and most of these patients were free of symptoms. Treatment quickly relieved symptoms and lowered plasma glucose in all patients. The Hb A1 concentration fell significantly with treatment such that after two months there was no significant difference between the three groups, although results remained above the normal range. These findings support the theory that the Hb A1 concentration reflects the blood glucose control over the previous one to two months and suggest that the duration of hyperglycaemia may be important in determining the Hb A1 concentration as well as the absolute blood glucose concentration.

Adult↗
PubMed1979

An ultrastructural study on the effects of warm ischaemia on the inosine-protected kidney.

Unperfused, saline-perfused and inosine-perfused rat kidneys were subjected to various times of warm ischaemia with and without resumption of blood flow. Tissues were examined with a transmission electron microscope. Inosine has a protective effect on the epithelial cells of the proximal convoluted tubules, where microvilli are less damaged by ischaemia than those of the proximal convoluted tubular cells of the control animals. Three is also a much higher ratio of autophagic vacuoles to lysosomes present in cells of inosine-treated kidneys, reflecting their ability to sequester and digest organelles damaged during ischaemia and thus protect themselves from degradation products. A major effect of inosine seems to be the preservation of the organelles and rush border of the cells of the proximal tubule during warm ischaemia.

Animals↗
PubMed1978

The ultrastructure of the male and female prostate of Praomys (Mastomys) natalensis. I. Normal, castrated and ovariectomised animals.

Male ventral and female prostates of Praomys (Mastomys) natalensis were examined with the electron microscope. The findings support and add to information obtained with the light microscope on tissues from normal, castrated and ovariectomised animals. Our results indicate that although the female prostate may be considered a homologue of the male ventral ventral prostate anatomically and histologically, there are differences in sub-cellular morphology and hormone dependence. Cells of the intact ventral prostate of the male are characterised by prominent dilated Golgi vesicles and electron-dense "mature secretory granules" seen in the apical region of the cell. In the cells of the female prostate these features are absent. These morphological differences reflect the influence of hormones upon the cells, as shown by the reduction of the dilated Golgi vesicles in the castrated male and conversely, their occasional presence in the cells of the oestrous female. Comparison of castrated and ovariectomised animals shows that the male ventral prostate is much more dependent on androgens than the female is on ovarian hormones. There are several modes of secretion in the male ventral and the female prostate. These are by acellular and cellular blebbing, by a variety of secretory vesicles into the acinar lumina, and by a system of "double walled" vesicles not previously described.

Animals↗
PubMed1978

Regan variant alkaline phosphatase in gastrointestinal carcinoma.

A fast-moving alkaline phosphatase band on polyacrylamide gel electrophoresis has been found in 6 patients with carcinoma of the liver and gastrointestinal tract. This isoenzyme resembled the placental isoenzyme in its inhibition by L-phenylalanine, its resistance to L-homoarginine inhibition and its molecular weight. However, it differed from the placental and Regan isoenzymes in its sensitivity to L-leucine and ethylenediaminetetra-acetic acid, its lower retardation by neuraminidase, its electrophoretic mobility and its decreased heat stability. The latter two properties also distinguished it from the Nagao isoenzyme. It was identified as the Regan Variant. The Regan Variant has hitherto been reported largely in hepatocellular carcinoma. In the presented paper we report its appearance in the sera of patients who have neoplasms in a variety of primary sites in the gastrointestinal tract. It is emphasized that, while the presence of the Regan Variant in serum may be taken as evidence of carcinoma, no conclusions can be drawn as to the site of the disease.

Adult↗
PubMed1978

The properties and clinical significance of some electrophoretically slow forms of alkaline phosphatase.

Sera from 8 patients with a marked slow-moving alkaline phosphatase band on electrophoresis were investigated. Inhibitor studies and treatment with neuraminidase showed that all the patients had slow bands with alkaline phosphatase properties resembling those of the liver or bone isoenzyme. In no case did the slow band resemble the intestinal isoenzyme. Immunoelectrophoretic and molecular weight studies indicated that the slow band consisted of an IgG-alkaline phosphatase complex of molecular weight 540 000. Serum from a patient with the slow band was able to bind liver or bone, but not intestinal, alkaline phosphatase from other patients to form the slow band. Serum from patients with the slow band probably contains an abnormal IgG molecule which can bind alkaline phosphatase in the ratio 2:1. No clinical condition was common to all 8 patients although most of them had either intestinal or lung disease.

Adult↗