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Biomedical subjects

W E Knox

Publications and source records attributed to W E Knox.

At least 19 recordsLinked to original sources
PubMed1984

Plasma clearance of carcinoembryonic antigen following hepatic metastatectomy.

Four patients with isolated hepatic metastases from primary colonic cancer presented with elevated plasma carcinoembryonic antigen (CEA) levels and underwent surgical metastatectomy . Plasma levels were monitored at two to six hour intervals in the immediate postoperative period and daily measurements were obtained for an extended period thereafter, up to 34 days. CEA clearance demonstrated a two-phase decrement with an initial rapid decay followed by a logarithmic decline with plasma half-lives of 66, 75, 150, and 208 hours. The first phase decline of 63% to 89% in circulating CEA levels immediately following tumor removal may reflect the fact that the plasma CEA is in dynamic equilibrium with the tumor CEA. The kinetics of the second-phase decline of CEA is variable and may be related to the quantitative circulating pool or to pathophysiologic processes influencing CEA metabolism or secretion in the liver. Quantitative assessment of tumor CEA content by immunoperoxidase techniques suggests a direct relationship between tissue levels and circulating plasma levels. The study of CEA kinetics may help in understanding the biology of tumor marker production and improve the capacity for clinical monitoring of plasma levels in conjunction with tumor therapy.

Carcinoembryonic Antigen↗
PubMed1983

Capacity of cyclic urea synthesis in neonatal rat liver.

The optimal conditions for the measurements of the capacity of cyclic urea formation was determined using tissue homogenate. Under these conditions, the capacity of cyclic urea synthesis in adult rat liver was 1.10 mumol/min/g wet tissue. On the other hand, the capacity of fetal liver was very low. After parturition, the capacity increased rapidly in 24 h to one-quarter of the adult level, and by weaning age it reached one-half the adult level.

Age Factors↗
PubMed1982

Cytosolic and mitochondrial isoenzymes of branched-chain amino acid aminotransferase during development of the rat.

The isoenzymic forms of branched-chain amino acid aminotransferase in mitochondria of rat tissues were compared with the better-known cytosolic forms in order to find any regular pattern of expression of these isoenzymes during development. Mitochondria of all tissues examined except brain contained only a type-I isoenzyme differing from the cytosolic type-I isoenzyme in heat stability and activation by mercaptoethanol. Foetal and adult brain mitochondria contained isoenzymes type III as well as type I. The large excess of type-I isoenzyme in foetal liver was localized in mitochondria, apparently of haematopoietic cells. The activity of this isoenzyme declined precipitously (by 80%) from day 19 of gestation at the same period and rate as does the volume fraction of haematopoietic cells that are then leaving the liver. Cortisol treatment accelerated the loss of these cells, and proportionally accelerated loss of the mitochondrial isoenzyme I. A development succession of type-I isoenzyme by the unique type II of liver parenchymal cell cytosols could not be demonstrated, since small, about equal, amounts of types I and II were always present in cytosols of foetal and adult liver. Developmental succession of isoenzymes within tissues was limited to cytosols and was demonstrated by the presence of cytosolic isoenzyme III in foetal and newborn skeletal muscle and kidney, organs which contain only isoenzyme I in the adult.

Age Factors↗
PubMed1980

Proline oxidase inhibition by free fatty acids of rat pancreas.

Proline oxidase activity was not measurable in pancreas homogenate but was measurable in pancreas slices. Moreover, added pancreas homogenate inhibited proline oxidase activity in rat liver mitochondria and several other tissues. The partially purified inhibitor from pancreas also inhibited the activity of glutamate, glucose 6-phosphate, NADH and succinate dehydrogenases. The inhibition was reversed by the addition of bovine serum albumin. Further studies to identify the inhibitor indicated that it consisted of free fatty acids that were enzymatically released after homogenization of pancreas. The free fatty acids released appeared to be derived primarily from triglycerides.

Animals↗
PubMed1979

Physical growth in phenylketonuria: I. A retrospective study.

A retrospective cross-sectional survey of phenylketonuria (PKU) was conducted in 1967. Questionnaires on 693 patients, clinically thought to have PKU, were reanalyzed to obtain information on growth in height and head circumference in patients with untreated and previously treated PKU. To provide a comparison to the growth findings of the Collaborative PKU Study, a definition of PKU was adopted to correspond to the one used in that study. Stature in 232 outpatients with untreated PKU was normal but, in 31 institutionalized individuals, the mean height was -1.4 standard deviations below the mean of a normal population. Head circumference in patients with untreated PKU was normal at birth, but showed an increasingly negative deviance with age and was -1.4 SD in untreated adults. Height measurements of 135 children with PKU in whom treatment was started before 121 days of age (age chosen to coincide with criteria for the Collaborative Study) had a significant reduction in height growth, -.8 SD. Head circumference measurements of 115 children treated for PKU were -.7 SD of normal. The depression in head circumference was less in treated subjects with PKU than in untreated ones of the same age. These findings are corroborated by a review of the literature, which contains no convincing report of normal growth during treatment of PKU.

Adolescent↗
PubMed1978

Assay of leucine aminotransferase in rat tissues and tumors.

A survey of leucine aminotransferase activities in an extensive variety of rat tissues further defined the unique distribution of this enzyme. Its reaction was measured in cell-free extracts under optimal conditions, and its product assayed both colorimetrically and with 14CO2 formed from it by decarboxylation with H2O2. The two methods agreed, though the second was more precise and dependable. In all the tissues and cell fractions examined, except adult liver, the activities with valine and isoleucine were parallel and similar to that with leucine. In adult liver there was low activity only with leucine, which is referable to a known isozyme (type II). Although the fraction of enzyme activity present in mitochondria has often been neglected, these studies showed that this portion in all tissues is about equal, more or less, to that of the more familiar soluble forms. There was good agreement between the relative concentrations of this enzyme in the commonly measured rat tissue preparations as determined here and in the more recently published studies. The unique occurrence of high levels of this enzyme in heart, kidney, brain and muscle, in that order, was confirmed. The unusual distribution of this enzyme was emphasized by the recognition that equally high or even higher levels also occurred in pancreas, lactating mammary gland and salivary gland. The relative amounts were less in normal, undifferentiated and in neoplastic tissues.

Amino Acids, Branched-Chain↗
PubMed1978

Guanase in reticulocytes and other rat tissues.

A sensitive and precise assay of guanase was based on the conversion of 14C-guanine to uric acid in the presence of excess xanthine oxidase. The enzyme was entirely soluble in rat tissues and no inhibitors of it were detected. The most active tissues were red blood cells, lung and lactating mammary gland, with more than twice the activity of liver. The contained blood could account for the low activity in adult skeletal muscle and some other tissues. All fetal tissues examined were without activity. Activity in mammary gland rose fourfold during lactation and dropped precipitously during involution, with a secondary rise associated in time with the loss of cells from the gland. Reticulocytes present normally and after hemorrhagic anemia appeared to account for substantially all of the high guanase activity in red blood cells. The guanase level could be used to predict the degree of reticulocytosis in rats within confidence limits of +/- 0.2%. The virtual absence of guanase in human red cells was confirmed, even in bloods containing elevated reticulocyte numbers.

Aminohydrolases↗
PubMed1978

Timing of gestation in rats by fetal and maternal weights.

Weights of embryonic and fetal rats increase with gestational age from Day 13 to 20 in a strictly logarithmic manner and then slow. Data for other rat strains published as long ago as 1915 show substantially the same growth curves and the same weights as the inbred Kx strain studied. During this late gestational period fetal weights doubled every 1.22 days. An earlier period of somewhat faster growth can be inferred. These growth rates are virtually the same as the maximum rates at which rat neoplasms can grow. A regression equation was constructed from which the ages of rat embryos can be predicted from their weights within confidence limits of +/- 0.24 days. A similar logarithmic increase of added weight in the pregnant dam was recognized by which pregnancies could be conveniently diagnosed as early as Day 7. These two procedures facilitate the routine production of embryos of known age for experimental purposes.

Animals↗
PubMed1977

Enzymes metabolizing delta1-pyrroline-5-carboxylate in rat tissues.

The direction and capacity for the metabolism of delta1-pyrroline-5-carboxylate in a number of rat tissues ere investigated by measuring the activities of delta1-pyrroline-5-carboxylate reductase, delta1-pyrroline-5-carboxylate dehydrogenase and proline oxidase. Each of these enzymes catalyzed unidirectional reactions in which delta1-pyrroline-5-carboxylate was either the substrate or product. Delta1-Pyrroline-5-carboxylate reductase activities that were much higher than any previously reported were obtained by avoiding its inactivation in the cold. delta1-Pyrroline-5-carboxylate dehydrogenase, previously said to act on both D- and L-isomers of delta1-pyrroline-5-carboxylate, acted only on the L-isomer. Proline oxidase could not be measured in two adult tissues, in which an inhibitor appeared after birth. The activity of delta1-pyrroline-5-carboxylate reductase significantly paralleled that of ornithine aminotransferase in 23 tissues, showing a widespread potential for proline synthesis from ornithine. An independently distributed potential in fewer tissues for proline degradation to alpha-oxoglutarate was shown by the significantly similar tissue distributions of proline oxidase. Delta1-pyrroline-5-carboxylate dehydrogenase and glutamate dehydrogenase. Reverse metabolism of glutamate or proline to ornithine would be atypical in rat tissues with these distributions of unidirectional enzyme reactions.

Animals↗
PubMed1977

Metabolism of arginine in lactating rat mammary gland.

Significant activities of the four enzymes needed to convert arginine into proline and glutamate (arginase, ornithine aminotransferase, pyrroline-5-carboxylate reductase and pyrroline-5-carboxylate dehydrogenase) develop co-ordinately in lactating rat mammary glands in proportion to the increased production of milk. No enzymes were detected to carry out the reactions of proline oxidation or reduction of glutamate to pyrroline-5-carboxylate. Minces of the gland converted ornithine into proline and into glutamate plus glutamine. These conversions increased during the cycle of lactation in proportion to the increased milk production and to the content of the necessary enzymes. The minced gland did not convert labelled ornithine into citrulline, confirming the absence from the gland of a functioning urea cycle, and did not convert labelled proline or glutamate into ornithine. A metabolic flow of labelled arginine to proline and glutamate in mammary gland was confirmed in intact animals with experiments during which the specific radioactivity of proline in plasma remained below that of the proline being formed from labelled arginine within the gland. It was concluded that arginase in this tissue had a metabolic role in the biosynthesis of extra proline and glutamate needed for synthesis of milk proteins.

Animals↗
PubMed1976

A comparative study of glytaminase isozymes in rat tissues.

The three kinds of glutamineses in rat kidney and liver were defined in comparative terms by their properties and were separately purified. Substantial purification was obtained by polymerization and depolymerization of the kidney isozyme that is activated by phosphate, These isozymes differ most strikingly in the activators of their reactions:maleate and a high concentration of phosphate, respectively, for the two kidney isozymes, and a low concentration of phosphate for the liver isozyme. The kidney isozyme that is activated by phosphate was also activated by a much lower concentration of ATP and by other complex phosphates. They also differ in physical properties: the maleate-activated isozyme was heat resistant (50 degrees C) and associated with insoluble submitochondrial particles; both phosphate-activated isozymes were heat sensitive and could be solubilized from their respective mitochondria; the phosphate-activated isozyme of kidney polymerized in phosphate-borate solution while that of liver did not. The characteristics of the kidney isozyme that was activated by high phosphate were shared by the glutaminases in adult brain, transplanted tumors, and in fetal liver and kidney. The similarity to the kidney enzyme was confirmed by the use of polymerization in phosphate borate of the isozyme from a mammary carcinoma to effect its purification.

Age Factors↗
PubMed1975

Types of arginase in rat tissues.

Significant amounts of arginase activity were found in homogenates of submaxillary salivary gland and epididymis, as well as of liver, kidney, mammary gland, and small intestine. The isoelectric point of arginase solubilized from kidney was at pH 7.0 in contrast to that of pH 9.4 characteristic of hepatic arginase in rat. The isozymic variants of arginase in the different tissues were identified by their electrophoretic migration on polyacrylamide gels and by titration of the enzymes against antibody prepared against purified rat liver arginase. Antibody titrations confirmed the indications obtained by electrophoresis that one type of arginase is limited to hepatic tissues (and possibly submaxillary gland) while the other type is found in all other tissues. The physiological role of arginase in hepatic tissues has been previously associated with the urea cycle; the possible function of arginase in proline synthesis in other tissues remains to substantiated.

Animals↗
PubMed1975

Peptidyl proline hydroxylase in adult, developing, and neoplastic rat tissues.

A sensitive assay system, optimally supplemented with tritiated protocollagen substrate and cofactors, is described which is suitable for determining the peptidyl proline hydroxylase (PPH) content of a wide spectrum of rat tissues. In most tissues, less than 50 percent of the total activity was soluble; the particulate portion of the activity (concentrated in the mitochondrial and microsomal fractions) was doubled by pretreatment with Triton X-100. Among normal adult tissues, lung had the highest total PPH activity (2.4 times that of liver) and small intestine had the lowest (25 percent that of liver). In brain and lactating mammary gland, the activity was similar to that in skin (60 percent of that in liver). Fetal tissues contained 3 to 8 times more PPH than the corresponding adult tissues, and a much lower portion of the total activity was soluble. In four tissues studied in detail (lung, liver, kidney, and brain), the total PPH declined rapidly during the last few days of gestation; brain attained its low adult value before term, whereas the other three tissues continued to decrease in the course of postnatal development. An injection of cortisol to fetal rats enhanced the decline of PPH in lung, liver, and skull. These experiments suggest that during normal differentiation the decline in collagen synthesis is initiated by fetal glucocorticoid secretion which is maximal on the 19th gestational day. PPH activity appears to be a sensitive indicator of neoplastic growth. In renal, mammary, muscle, and hepatic tumors, the PPH activities were 4 to 10 times higher than in the cognate adult tissue. Even in well-differentiated, slowgrowing tumors, the activity was considerably higher than in any normal, mature, or immature tissue, with the exception of the skull and lung of the 19-day-old fetus.

Animals↗