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S Granick

Publications and source records attributed to S Granick.

At least 37 records · Page 2Linked to original sources

Cognitive and psychosocial differences between I and E locus of control aged persons.

An abbreviated version of Rotter's Locus of Control (LOC) Scale was administered to 437 elderly subjects living in a variety of settings in an urban community. The group (n = 199) which scored below the median (internal orientation) was compared with the group (n = 238) which scored at or above the median (external orientation) on an array of 37 cognitive and psychosocial variables. Significant differences, mostly favoring the internal subjects, were found on 13 of the variables, suggesting relatively better self-reported health status, cognitive, and personal-social functioning on their part. These results are in general agreement with most other reports dealing with the relationships between LOC responses of the aged and their psychosocial functioning. Step-wise multiple regression analysis of the intercorrelations among the 37 variables and LOC show only seven are significant and these account for no more than 13 percent of the variance. The overall impression is that LOC has a reliable relationship to limited aspects of cognitive and psychosocial functioning, but that the power of its predictive effectiveness is still quite limited.

Aged↗

Psychologic assessment technology for geriatric practice.

Psychologic assessment is an integral aspect of the comprehensive functional assessment of geriatric patients. Medical areas in which psychologic testing and evaluation can be of significant service in the diagnosis and formulation of treatment plans include psychiatric and neurologic disturbances, psychosomatic disorders, circulatory diseases (especially hypertension), diabetes, chronic pain, sexual dysfunctions, and gastrointestinal problems. In the effort to gain an understanding of the total patient, it is important to clarify the effect of physical condition on a person's psychologic reactions as well as the impact of psychologic states on his/her biologic status. This orientation is particularly important in dealing with elderly patients because the interaction between the physical and the psychologic in this age group is exceedingly strong and significant. Despite the fact that research in the psychology of the aged is of long standing, the attention given by clinical psychologists to the provision of services to geriatric patients has been quite limited until recently. Many psychologic tests have been developed during the past 70 years, but relatively few of them have been standardized for use with the aged. Of late, however, this has been changing. Several tests have been adapted, and some new ones have been organized with the needs and characteristics of the aged in mind. Closer attention has been paid to psychometric principles in the development of the tests, leading to the organization of useful norms and the demonstration of proper levels of reliability and validity. Accordingly, the state of the art of psychologic assessment of the aged is currently rather limited, but the outlook for the near future appears encouraging. In evaluating the condition of a geriatric patient, the clinical psychologist normally generates data through observations, testing, and interviewing. The resulting report covers the following areas: 1) adaptation to the examination and behavioral characteristics during the procedure, 2) cognitive functioning, 3) visual motor coordination and perception of spatial relationships, and 4) personality characteristics and mental health status. Data for the first area are normally derived by the examiner from observations and subjective impressions of the patient's behavior. For each of the other areas the information is obtained through standardized tests. In this discussion, some of the principal assessments that are currently available are reviewed and evaluated for their usefulness with the aged.

Aged↗

Synthesis and secretion of plasma proteins by embryonic chick hepatocytes: changing patterns during the first three days of culture.

A simple model system is described for studying synthesis of plasma proteins. The system is based on chick embryo hepatocytes in primary monolayer culture which synthesize a broad spectrum of plasma proteins and secrete them into the culture medium. The secreted proteins are stable and consist almost exclusively of plasma proteins. The cultured cells are nonproliferating hepatic parenchymal cells whose cell mass remains constant in culture. By a modification of Laurell's rocket immunoelectrophoresis, the secreted plasma proteins can be detected in nanogram amounts in 3 microliter of unconcentrated culture medium. Kinetics of secretion are obtained by sequential assay of proteins accumulating in the medium. In this system it is demonstrated that: (a) intracellular plasma protein levels are equivalent to less than 5% of the daily secretion; (b) synthesis and secretion are continuous; and (c) the overall half-time for plasma protein movement along the secretory pathway is less than 10 min. From these results, it follows that the rate at which the plasma proteins are secreted gives a valid estimate of their rate of synthesis. This feature of the culture and the sensitivity of the assay allow routine measurements of plasma protein synthesis without disruption of the cells and without the use of radioisotopes. It is shown, furthermore, that the overall rate of plasma protein synthesis in cultured hepatocytes is constant over a 3-day period and is similar to that of the intact liver. 3,000,000 cells, containing 1 mg cell protein, synthesize 0.2 mg of plasma proteins daily, amounting to one-fifth of hepatocellular protein synthesis. Under the conditions used, albumin synthesis steadily decreases with culture time whereas the synthesis of many other plasma proteins increases. The observed phenotypic changes and reorganization of plasma protein synthesis illustrate how the system may be exploited for studying the regulatory processes governing plasma protein synthesis.

Animals↗

Delta-Aminolevulinic acid synthase from chick embryo liver mitochondria. I. Purification and some properties.

The purification of hepatic delta-aminolevulinic acid synthase (EC 2.3.1.37) was accomplished from chick embryo liver mitochondria, which had been treated with the combination of drugs, 2-allylisopropylacetamide and 1,4-dihydro-3,5-dicarbethoxycollidine to produce a high starting level of enzyme activity. After extraction from the mitochondria by sonication, the enzyme was purified to a final specific activity of over 10,000 nmol of aminolevulinate formed/30 min/mg of protein/37 degrees, using the techniques of Sephadex chromatography, ammonium sulfate fractionation, affinity chromatography for pyridoxal phosphate, and preparative isoelectric focusing. An isoelectric point of 7.0 and a molecular weight of 87,000 were obtained for the native enzyme. The subunit molecular weight of 49,000, obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggested it was a dimer. The enzyme was inhibited by p-chloromercuribenzoate and N-ethylmaleimide, stimulated by cations and exhibited an ultraviolet absorption spectrum characteristic of pyridoxal 5'-phosphate enzymes with absorption maxima at 325 and 420 nm.

5-Aminolevulinate Synthetase↗

Relationships between hearing loss and cognition in normally hearing aged persons.

The relationships between mild hearing losses and cognitive functioning were studied for two independently selected samples of aged subjects whose hearing was within normal limits. One group had 47 males of mean age 71.5 (SD 4.8) who were selected for their excellent health status. The second group consisted of 38 females of mean age 75.9 (SD 5.3), all of whom had some significant physical pathology. Hearing losses at various frequency levels (from 125 to 8000 cps) were correlated with performance on cognitive tests such as the WAIS, with age effects then being partialled out. The results reveal substantial associations between hearing losses and scores achieved on the intellectual measures for both samples. Verbal type tests show these relationships much more extensively than the performance tests. The findings imply that aged subjects may be more intellectually capable than their test performances suggest and that hearing is an important variable to be considered in the assessment of their cognitive functioning.

Aging↗

The transport of hemin and protoporphyrin across the plasma membrane of chick embryo liver cells in culture.

Primary monolayer cultures of chick embryo hepatocytes can be cultured in a chemically defined medium (Ham F-12) containing insulin. The absence of serum from the medium permitted a study of the effects of added serum proteins on the transport of hemin and protoporphyrin across the plasma membrane of the hepatocyte. As the criterion of hemin uptake we used its unique and selective activity in repressing the induced synthesis of delta-aminolevulinate synthetase by various chemicals. Movement of hemin into the cells is rapid and does not require added serum proteins. Hemin represses the induced synthesis. The repression by hemin is decreased 50% when the molar ratio of hemin to human serum albumin (6.5 muM) is 1 :2, i.e., where the calculated concentration of dissociated hemin is 10(-8) M. Apparently serum albumin does not enter the cells; it decreases entry of hemin into the cells by virtue of its high affinity for hemin. Compared to human serum albumin, bovine serum albumin and chicken serum albumin, under the same conditions, have a much lower affinity for hemin and scarcely influence the repression effect by hemin. Protoporphyrin can be specifically caused to accumulate in the cytosol, and uroporphyrin in the nucleus of the hepatocytes by the use of different inducers of delta-aminolevulinate synthetase. Protoporphyrin, but not uroporphyrin, is released rapidly from the cells when the moles of human serum albumin added to the medium are 5 times that of porphyrin. This culture system may provide a useful model for studying the mechanism of transport of organic anions across the hepatocyte plasma membrane.

5-Aminolevulinate Synthetase↗

The biosynthesis of delta-aminolevulinic acid from the intact carbon skeleton of glutamic acid in greening barley.

The formation of delta-aminolevulinic acid in mammals birds, yeast and some bacteria is known to take place by the ALA-synthetase assisted coupling of glycine with succinylCoA. Plants, however, form the bulk of their delta-aminolevulinate in another way. We present evidence here that the intact, 5-carbon chain of glutamate becomes that of delta-aminolevulinate. Greening barley was fed specifically labelled glutamate and levulinate to create a pool of labelled delta-aminolevulinate. Levulinate, a competitive inhibitor of ALA-dehydratase, prevents the metabolism of delta-aminolevulinate. The carbon chain of the labelled delta-aminolevulinate was broken into formaldehyde and succinate by periodate to determine the position of the label. It was found that the C1, carboxyl carbon of glutamate becomes the amino-bearing (C5) carbon of delta-aminolevulinate and forms the formaldehyde on cleavage. delta-Aminolevulinate formed from C3,4-labelled glutamate bears its label in the succinate cleaved fragment. We conclude that during the light induced development of the plastid in barley the carbon chain of delta-aminolevulinate is formed from the intact chain of glutamate. ALA-synthetase catalyzed the formation of delta-aminolevulinate from glycine and succinylCoA cannot play a quantitively important role in the formation of chlorophyll.

Aminolevulinic Acid↗

Effects by heme, insulin, and serum albumin on heme and protein synthesis in chick embryo liver cells cultured in a chemically defined medium, and a spectrofluorometric assay for porphyrin composition.

Primary chick embryo liver cells, which had been previously cultured in Eagle's medium containing 10% fetal bovine serum, had the same characteristics (inducibility of delta-aminolevulinic acid synthetase and synthesis of plasma proteins) when cultured in a completely defined Ham F-12 medium containing insulin. Insulin was active in the physiological range; 2 to 3 nM were sufficient to increase the induced delta-aminolevulinic acid synthetase to 50% of the maximum effect obtained with a saturating amount of insulin (30 nM). Serum albumin added to the Ham-insulin medium caused protoporphyrin but not uroporphyrin, generated in the cultured liver cells, to be transferred to the medium. As little as 10 mug of human serum albumin per ml caused the transfer of one-half of the protoporphyrin. Bovine serum albumin was only about 1/30 as effective. A spectrofluorometric method and calculation procedure are described for quantitation, in the nanomolar range, of total porphyrin and the percentage of this that is protoporphyrin or uroporphyrin plus coproporphyrin. The method is satisfactory for the measurement of porphyrins generated by 1 mg wet weight of cells in culture in 20 hours. Heme (0.1 to 0.3 muM), when added to the medium as hemin, human hemoglobin, or chicken hemoglobin, specifically inhibited the induction of delta-aminolevulinic acid synthetase by one-half. This high sensitivity for heme was observed under conditions in which the defined medium was free of serum and where a chelator of iron was added to the medium to diminish the synthesis of endogenous heme. Heme endogenously generated from exogenous delta-aminolevulinic acid also inhibited the induction; chelators of iron prevented this inhibition. The migration of heme from the mitochondria to other portions of the cell is discussed in terms of the affinities of different proteins for heme. A hypothesis of a steady state of liver heme metabolism, controlled by the concentration of "free" heme, is presented. The different effects of heme on the synthesis of a number of proteins are summarized.

5-Aminolevulinate Synthetase↗

Snythesis and differentiation of plasma proteins in cultured embryonic chicken liver cells: a system for study of regulation of protein synthesis.

A new system is described for studying the control of protein synthesis. In a monolayer culture of chick embryo liver cells, plasma proteins are synthesized for three days at in vivo rates. The plasma proteins are secreted into the culture medium and without concentration are detected there simply and sensitively by a modified Laurell electronimmunoassay. Secretion of the newly synthesized plasma proteins occurs within 30 min of their synthesis. Thus, rates of synthesis of the plasma proteins can be followed readily from rates of their accumulation in the culture medium. This system has the following advantages for the study of protein synthesis: cells do not have to be disrupted for the assay; the cell population can be followed over several days; it is not necessary to label the proteins radioactively; and turnover of plasma proteins is negligible and need not be taken into account. The usefulness of the system is illustrated by a number of findings. The spectrum of plasma proteins synthesized in culture changed qualitatively and quantitatively. Albumin synthesis steadily decreased with culture time and stopped at the third day, whereas the synthesis of some new plasma proteins ("adult") was induced. These qualitative changes suggest differential gene expression in culture and a special control of albumin synthesis in vivo, different from the synthesis of the other plasma proteins. Quantitative changes in the rates of synthesis of specific plasma proteins suggest a competition among their messenger RNAs for components of the translational machinery. Insulin has a differential effect on the synthesis of specific plasma proteins at concentrations within the physiological range of the hormone.

Animals↗

Biosynthesis of delta-aminolevulinic acid from the intact carbon skeleton of glutamic acid in greening barley.

The customary route in animals and bacteria for delta-aminolevulinic acid biosynthesis is from glycine and succinyl CoA, catalyzed by the enzyme delta-aminolevulinic acid synthetase [succinyl-CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37]. Attempts to demonstrate this route in plants have been unsuccessful. Evidence is given for a new enzymic route of synthesis of delta-aminolevulinic acid in plants. This route involves the incorporation of the intact five-carbon skeleton of glutamic acid into delta-aminolevulinic acid. Demonstration of the new pathway in plants has been made by feeding specifically labeled [14C]glutamic acid to etiolated barley shoots greening in the light. In the presence of levulinate, a competitive inhibitor of delta-aminolevulinic acid dehydrastase [porphobilinogen synthase; delta-aminolevulinate hydro-lyase (adding delta-aminolevulinate and cyclizing); EC 4.2.1.24], delta-aminolevulinate accumulates. The delta-aminolevulinate formed was chemically degraded by periodate to formaldehyde and succinic acid. The C5 (formaldehyde) fragment was separated, as the 5,5-dimethyl-1,3-cyclohexanedione (dimedone) derivative, from the C1-C4 (succinic acid) fragment. The C5 atom contained radioactivity predominantly derived from C1 of glutamic acid. Conversely, the labeled C3 and C4 atoms of glutamic acid were found primarily in the succinic acid (C1-C4) fragment of delta-aminolevulinate. This labeling pattern for delta-aminolevulinic acid is consistent with a biosynthetic route utilizing the intact five-carbon skeleton of alpha-ketoglutarate, glutamate, or glutamine, and is inconsistent with the delta-aminolevulinic acid synthetase pathway utilizing glycine and succinyl CoA as precursors.

Aminolevulinic Acid↗

A microassay for uroporphyrinogen I synthase, one of three abnormal enzyme activities in acute intermittent porphyria, and its application to the study of the genetics of this disease.

A new spectrofluorometric assay is described for quantitating uroporphyrinogen I synthase (EC 4.3.1.8) activity in volumes of human blood as small as 2 mul. By this sensitive assay the inheritance of the enzyme's activity has been studied and the genetic defect for acute intermittent porphyria has been confirmed to be autosomal dominant in nature. There is a 3-fold range of uroporphyrinogen I synthase activity in erythrocytes in the normal population, with a mean V(max) +/- SD of 35.7 +/- 8.4 nmol of uroporphyrinogen I formed per ml of erythrocytes per hr, at 37 degrees . One-half this level of enzyme activity (18.0 +/- 5.0) is found in erythrocytes from patients with clinically manifest acute intermittent porphyria; and in erythrocytes from those of their relatives, including prepubertal children, who have the latent gene defect for the disease. The K(m) of erythrocyte enzyme of normal people is 12.3 +/- 3.9 muM, whereas the K(m) of the erythrocyte enzyme of patients with acute intermittent porphyria is 6.2 +/- 3.9 muM, as determined on whole blood lysates. Three enzymic changes have now been identified in patients with acute intermittent porphyria; a high level of delta-aminolevulinate synthase activity; a low level of uroporphyrinogen I synthase activity; and a deficiency of steroid Delta(4)-5alpha reductase activity.

Adolescent↗