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Because the sites of action of pectinase and cellulase are the middle lamella and the primary cell wall, and the site of synthesis of these enzymes is within the plasmalemma, they must be secreted before they can cause abscission (Morn~, 1968; Abeles and Leather, 1971; Abeles et al. If pectinase and cellulase are required to dissolve the middle lamella and weaken the primary cell wall of cells in the abscission zone, as appears to be the case, then an explanation of inhibition or promotion of abscission by environmental and hormonal factors must eventually tie these factors to regulation of synthesis, secretion and activity of these hydrolytic enzymes. However, because of interactions, it will be necessary to mention more than one hormone under each heading. This response caused Addicott and co-workers to propose the auxin-gradient theory of abscission control (Addicott eta!. According to this theory, the relative concentrations of auxin on each side of the abscission zone (the auxin gradient) are more important than the absolute auxin concentration. Rubinstein and Leopold (1963) found that time of auxin application was just as important as concentration. Abeles (1967) explained the auxin-gradient effect on the basis of auxin stimulation of ethylene production, the polar movement of auxin, and the opposing effects of auxin and ethylene in inhibiting and promoting abscission, respectively. When applied distally, auxin moves into the abscission zone and inhibits abscission. When applied proximally, however, auxin is unable to move rapidly into the abscission zone (against its normal direction of polar movement). Ethylene can move in any direction and its promotive effect becomes dominant when auxin is applied to the proximal side of the abscission zone. The time-dependent effect of auxin in either inhibiting or promoting abscission was reviewed and explained by Leopold (1971). During stage I, the period during which auxin inhibits abscission, the tissue is relatively insensitive to ethylene. Despite the vast amount of research that has been done on auxin, the exact mechanism by which it inhibits abscission has not been elucidated. The fact that the increase in cellulase activity was also suppressed by application of cycloheximide (Abeles, 1969; Ratner et a!. Although speculative, another mechanism by which auxin might inhibit abscission is through an effect on membranes. Auxin has been reported to maintain membrane integrity and selective permeability (Sacher, 1957; Abeles, 1968; Helgerson et at. Two mechanisms of action have been established: (a) slower transport and increased destruction of auxin, and (b) stimulation of synthesis of pectinase and cellulase in the abscission zone. Morgan and co-workers also showed that ethylene slows auxin transport (Morgan and Gausman, 1966; Morgan eta/. Because auxin prevents or delays abscission, both the destruction and the slowed transport of auxin should promote abscission by decreasing the amount of auxin that reaches the abscission zone. Perhaps an even more direct action of ethylene is its stimulation of synthesis of pectinase (Riov, 1974) and cellulase (Horton and Osborne, 1967; Abeles, 1968, 1969; Ratner eta/. Not only does ethylene stimulate the synthesis of cellulase, it also promotes the release or secretion of cellulase through the plasma membrane and into the cell wall (Abeles and Leather, 1971; Abeles eta!. It decreases the auxin content of the abscission zone, and it stimulates the synthesis of enzymes that weaken the middle lamella and cell wall. More recent evidence has cast doubt on its role as a direct regulator of fruit abscission. Therefore, its effects could be indirect (through increased ethylene) rather than direct. Cooper and Horanic (1973) used low pressures to remove ethylene from treated citrus. Hypobaric pressures prevented the fruit drop that normally occurs after spraying the fruit with cycloheximide, thereby implicating ethylene in the abscission induced by cycloheximide. Gibberellins may retard abscission of intact fruit by mobilizing nutrients to that fruit and by stimulating growth (Addicott, 1970). Another consideration is the fact that there are many gibberellins and they may not all have the same effects. Gibberellin content remained low in bolls destined to abscise and increased in retained bolls (Cognee, 197 5). Rodgers (1981 c) reported maximum gibberellin activity at about 2 and I 5 days after anthesis, ages at which he found relatively little boll abscission (Rodgers, 1980a). Cytokinins- the role of cytokinins in regulating abscission appears to be indirect. They may either inhibit or promote abscission, depending upon time and site of application (cf.

At that time the magical notions will begin to disappear from courtroom trials of diminished capacity which often turn into trials of the drugs themselves as good or evil. Forensic Psychiatry in the Defense of Diminished Capacity Los Angeles: University SouthernCalifornia, 1976 Szasz, T. The technical papers of the Second Report of the National Commission on Marihuana and Drug Abuse. Department of Psychiatry and Biobehavioral Sciences School of Medicine University of California, Los Angeles Los Angeles, California 90024 Mailing Address: Ronald K. Despite a continuing search for commonalities across the various forms of substance abuse, it has been difficult to identify factors which apply equally to the abuse of opiates, alcohol, stimulants and hallucinogens. The traditional focus on specific syndromes associated with the abuse of certain drugs. Moreover, known differences in the pharmacological and behavioral consequences of alcohol, heroin, cocaine and phencyclidine intoxication would appear to argue against the notion that any meaningful similarities could be found. Re-examination of the behavioral consequences of drug use and abuse suggest that one pervasive factor has often been overlooked. Many drugs of abuse have now been shown to have aversive consequences during intoxication. These data have led to the hypothesis that "aversive" consequences may be an important factor in the control of many forms of drug abuse (Mello 1977). Recent findings relevant to this hypothesis will be examined in the remainder of this review. One basic assumption is that drug self-administration behavior is controlled or maintained by its consequences. Therefore, any consistent consequence which transcends drug specific effects may be a common factor which contributes to the maintenance of substance abuse. It would be convenient if the initial drug experience was so overwhelmingly positive that repeated drug use would be almost inevitable. Yet the reported effects of acute doses of opiates, barbiturates, alcohol and nicotine summarized in Table 1 do not appear to be especially appealing. These drugs each produce a variety of somatic and emotional effects that would seem disadvantageous to the user. Yet, despite these "aversive" consequences of initial drug use, many individuals persist in self-administration of these same drugs to the point of abuse and addiction. It has often been observed that alcohol addicts tend to have a clear recollection of their "first drink" (Kuehnle, Anderson, and Chandler 1974). However, clinical impressions suggest that the first drink was not memorable because of its relaxing, euphorigenic, tension-reducing, or self-actualizing effects for the drinker (Kuehnle, Anderson, and Chandler 1974; Catanzaro 1968). It is more likely that the future alcoholic drank to the point of intoxication with associated despondency, nausea and vomiting. The process by which an initial aversive drug experience becomes translated into a repetitive drug use pattern is not understood. It could be postulated that with the development of drug tolerance, these seemingly unpleasant somatic and emotional effects 290 undergo a transition to a more positive state, i. Alternatively, it could be postulated that the initial dysphoria, nausea, and vomiting is an integral part of the reinforcing properties of subsequent drug abuse. It is now evident that drug abuse is maintained despite the recurrence of these seemingly aversive consequences. However, the immediate consequences of drug use are usually believed to be sufficiently positive to outweigh these long-term effects. If in fact, abused drugs consistently produced relaxation, euphoria, relief from anxiety, tranquility and serenity, then chronic drug use and abuse might be more understandable. However, common expectancies about drug related pleasures have not been confirmed in clinical studies of addicts during intoxication. Direct observations of intoxicated individuals are often discordant with retrospective self-reports of drug effects obtained during a period of sobriety. This discrepancy is particularly troublesome since most of our information about the effects of abused drugs is based on retrospective reports of users during sobriety. It now appears that increases in dysphoria, anxiety, and agitation frequently accompany chronic intoxication, both with alcohol (Mello and Mendelson 1978) and with heroin (Mirin et al. These findings challenge the traditional view of the behavioral effects of these drugs, and are one basis for the idea that "aversive" consequences are important in the maintenance of drug self-administration behavior.

A degenerative condition of a cell nucleus marked by clumping of the chromosomes, hyperchromatism, and shrinking of the nucleus. Reactive oxygen species scavenging capacity related to the converstion or consumption of reactive oxygen species, including both radicals and non-radicals. A disk-shaped, biconcave cell in the blood that contains hemoglobin lacks a nucleus, and transports oxygen and carbon dioxide to and from the tissues. In rods the photopigment is in stacks of membranous disks separate from the outer cell membrane. Rods are more sensitive to light than cones, but rod mediated vision has less spatial and temporal resolution than cone vision. Any of the elongated cells located in the seminiferous tubules of the testis, and whose main function is to nourish the spermatids attached to it. The physical magnitude, extent, or bulk: relative or proportionate dimensions of a cell. A principal type of white blood cell that completes maturation in the thymus and that has various roles in the immune system, including the identification of specific foreign antigens in the body and the activation and deactivation of other immune cells. An irregularly shaped, disclike cytoplasmic fragment of a megakaryocyte that is shed in the marrow sinus and subsequently found in the peripheral blood, where it functions in clotting. A platelet contains granules in its central part (granulomere) and, peripherally, clear protoplasm (hyalomere), but no nucleus, is about one third to one half the size of an erythrocyte, and contains no hemoglobin. Also: hsd17b12, 17-beta-estradiol 17dehydrogenase, very-longchain 3-oxoacyl-CoA reductase, 17-beta-hydroxysteroid dehydrogenase 12, 3-ketoacylCoA reductase. Aneuploidy is the chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes, chromosome pairs, or chromosome fragments. Also: Rhag, Erythrocyte membrane glycoprotein Rh50, Rhesus blood group family type A glycoprotein. Beta-Actin is a muscle protein that is the chief constituent of the Z-band myofilaments of each sarcomere. Small basic protein purified from pig brain, a member of the family of neurotrophic factors that also includes Nerve Growth Factor and neurotrophin 3. In the brain brain-derived neurotrophic factor has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. The protooncogene protein c-fos codes for a nuclear protein which is involved in growth-related transcriptional control. Mutation: a change in form, quality or some other characteristic; in genetics - a permanent transmissible change in the genetic material. Chromatin exists in two states, euchromatin and heterochromatin, with different staining and functional properties. Modification of the normal chromosome complement due to deletion, duplication, or rearrangement of genetic material. Chromosome breakage - A type of chromosomal aberration which may result from spontaneous or induced breakage. Alkylating agents, various types of irradiation and chemical mutagens have been found to cause induced chromosomal breakage. Also: Cldn11, Oligodendrocyte transmembrane protein, Oligodendrocyte-specific protein. Also: cytochrome P450, family 19, subfamily A, polypeptide 1b, cyp19a1b protein, cyp19a1b, P450aromB, zgc:92614. Also: Cytochrome c6, petJ, Cytochrome c-552, Cytochrome c-553, Cytochrome c553, Soluble cytochrome f. Part of an enzyme which converts androgens to oestrogens by desaturating ring a of the steroid. Also: cyp3c3, Cytochrome P450, family 3, subfamily c, polypeptide 1 like 2, cyp3c112. Also: Dgat1, Acyl-CoA retinol O-fattyacyltransferase, Retinol O-fattyacyltransferase, Diglyceride acyltransferase. A stage of meiotic prophase which follows the pachytene and during which the paired homologous chromosomes begin to separate and chiasmata become visible. Induction of a dominant lethal event after exposure to a test substance indicates that the substance has affected germinal tissue of the test species.

An enzyme that catalyses the incorporation of one oxygen atom of molecular oxygen into benzo(a)pyrene. Measurement Definition A glucosidase enzyme that acts upon 1->4 bonds linking two glucose or glucose-substituted molecules. It is an exocellulase with specificity for a variety of beta-D-glycoside substrates. It catalyzes the hydrolysis of terminal non-reducing residues in beta-D-glucosides with release of glucose. The rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase. A zinc metallo-enzyme that catalyzes the transfer of a methyl group from betaine to homocysteine to produce dimethylglycine and methionine respectively. This enzyme belongs to the family of transferases, specifically those transferring onecarbon group methyltransferases and participates in the metabolism of glycine, serine, threonine and also methionine. Also: betainehomocysteine methyltransferase; betainehomocysteine transmethylase, Betaine homocysteine methyltransferase. Enzyme reaction hydrolysis of terminal non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides. In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs. It functions in the control of a number of cellular processes, including proliferation, embryonic development and apoptosis. An enzyme that has several functions in the cell, including regulation of glycogen, sugar, and lipid metabolism. The enzyme is involved in the detoxification of Xenobiotics and the activation of ester and of amide Prodrugs. Caspase-8 is a member of the cysteine proteases, which are implicated in apoptosis and cytokine processing. Like all caspases, caspase-8 is synthesized as an inactive single polypeptide chain zymogen procaspase and is activated by proteolytic cleavage, through either autoactivation after recruitment into a multimeric complex or trans-cleavage by other caspases. A red crystalline enzyme that consists of a protein complex with hematin groups and catalyzes the decomposition of hydrogen peroxide into water and oxygen. One of a number of enzymes each of which catalyzes the hydrolytic cleavage of specific peptide bonds. A lysosomal cysteine proteinase which hydrolyzes proteins, with a specificity resembling that of papain. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin b has been found to be involved in demyelination, emphysema, rheumatoid arthritis, and neoplastic infiltration. A blue, copper-containing globulin that may play a part in erythropoiesis and oxygen reduction. An enzyme that cleaves the glycosidic bonds in chitin, thereby breaking down the polysaccharide structural component of the hard outer covering of many animals and of the cell wall of fungi. Synonym: cpfoase A membrane-bound cytochrome p450 enzyme that catalyzes the 7-alpha-hydroxylation of cholesterol in the presence of molecular oxygen and nadph-ferrihemoprotein reductase. This enzyme, encoded by cyp7, converts cholesterol to 7-alpha-hydroxycholesterol which is the first and rate-limiting step in the synthesis of bile acids. Collagens are the major fibrous component of animal extracellular connective tissue. Heme is an essential component of iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood). The production of heme is a multi-step process that requires eight different enzymes. A zinc-containing sialoglycoprotein that is used to study aminopeptidase activity in the pathogenesis of hypertension.