Anti-thrombotic therapy prescribed for patients with non-rheumatic atrial fibrillation (Scot Med J 1994:39;110-111)
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Aged↗
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On variation, inheritance and chemical interrelationships of monoterpenes in scots pine (Pinus silvestris L.).
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Chromatography, Gas↗
Scots nail their flags to the mast.
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Humans↗
A melange of meningiomas (Scot Med J 1998; 43: 117-118)
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Brain Neoplasms↗
Autologous tunica vaginalis and subcapsular orchiectomy: a hormonal therapy for prostate cancer.
Two novel surgical procedures that combine an autologous tunica vaginalis pedicle graft (TVG) with a subcapsular orchiectomy (SCOT) were evaluated in asymptomatic patients with rising prostate-specific antigen (PSA) values following radiation therapy, a radical retropubic prostatectomy, or a newly diagnosed prostatic cancer with bony metastasis. In the SCOT I procedure, the TVG was secured to the inner wall of the tunica albuginea. In the SCOT II procedure, the TVG was folded and secured to the external wall of the tunica albuginea. Between December 1, 1999, and July 1, 2000, 26 patients were offered hormonal therapy. Twelve patients selected the SCOT I procedure, 12 selected a luteinizing hormone-releasing hormone (LHRH) agonist, and 2 selected a bilateral total orchiectomy (BTO). Because the cosmetic outcome of the SCOT I procedure was less than ideal, this procedure was modified in December 2001. Between December 1, 2001, and July 1, 2002, 28 hormonal candidates were evaluated. Twelve patients selected the SCOT II procedure, 11 selected an LHRH agonist, and 5 selected a BTO. Preoperative measurements of the testicular area and PSA were obtained. During postoperative visits, the total testosterone, PSA, and testicular area were determined, and the Fugl-Meyer questionnaire (FMQ) and SCOT-specific questionnaire (SSQ) were completed. Between March 1, 2000, and December 1, 2002, 10 patients underwent a BTO. This group was the control for the postoperative SCOT total testosterone values. Sixty-three percent of the mean preoperative testicular area was preserved in the SCOT II group vs 43% in the SCOT I group at the 9- to 12-month visit (P <.01). The mean postoperative total testosterone values for the SCOT I, SCOT II, and BTO groups were in the castrate range. No statistically significant difference was noted between the preoperative and postoperative FMQ scores among the SCOT I and SCOT II groups. Eighty-three percent of the SCOT II patients experienced no change in masculine identity, and 58% noted no change in testicular size. One hundred percent of the SCOT I patients experienced no change in masculine identity and noted no change in testicular size. The SCOT II procedure preserved a greater testicular area than the SCOT I. Both SCOT procedures achieved castrate levels of total testosterone and maintained masculine identity in 83%-100% of patients.
Aged↗
Prenatal diagnosis of succinyl-coenzyme A:3-ketoacid coenzyme A transferase deficiency.
Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is a rare disorder of ketone body catabolism. In the present study, we prenatally diagnosed SCOT deficiency in a fetus in a family of which the proband was the first patient with SCOT deficiency identified in Japan, by analysis of enzyme activity levels in samples of chorionic villi and cultured amniocytes. In the fetus of the family, SCOT activity was not detected in either chorionic villi or cultured amniocytes. Since the levels of SCOT activity in control chorionic villi were close to our minimal detectable level and were much lower than those in control cultured amniocytes, enzyme assay in cultured amniocytes was more feasible than that in chorionic villi for prenatal diagnosis of SCOT deficiency. No elevated accumulation of 3-hydroxybutyrate or acetoacetate was detected in the amniotic fluid of the fetus. To our knowledge, this report is the first of prenatal diagnosis of SCOT deficiency.
3-Hydroxybutyric Acid↗
Enzymes of ketone body utilization in human tissues: protein and messenger RNA levels of succinyl-coenzyme A (CoA):3-ketoacid CoA transferase and mitochondrial and cytosolic acetoacetyl-CoA thiolases.
We describe the distribution in human tissues of three enzymes of ketone body utilization: succinyl-CoA:3-ketoacid CoA transferase (SCOT), mitochondrial acetoacetyl-CoA thiolase (T2), and cytosolic acetoacetyl-CoA thiolase (CT). Hereditary deficiency of each of these enzymes has been associated with ketoacidosis. Physiologically the two mitochondrial enzymes have different roles: SCOT mediates energy production from ketone bodies (ketolysis), whereas T2 functions both in ketogenesis and ketolysis. In contrast, CT is implicated in cytosolic cholesterol synthesis. We investigated the tissue distribution of these enzymes in humans by quantitative immunoblots and by Northern blots. In most tissues, polypeptide and mRNA levels were proportional. CT and T2 proteins were detected in all tissues examined. CT levels were highest in liver, were 4-fold lower in adrenal glands, kidney, brain, and lung, and were lowest in skeletal and heart muscles. T2 was most abundant in liver but substantial amounts were present in kidney, heart, adrenal glands, and skeletal muscle. SCOT was detected in all tissues except liver: myocardium > brain, kidney and adrenal glands. The relative amounts of T2 and SCOT were similar in all tissues except for liver (T2 > > SCOT) and brain (SCOT > T2). The observed distribution of SCOT, T2, and CT is consistent with current views of their physiologic roles.
Acetyl-CoA C-Acetyltransferase↗
Ketone bodies could support the motility but not the acrosome reaction of mouse sperm.
Ketone bodies, D-beta-hydroxybutyrate and acetoacetate, produced by the metabolism of fatty acids, are an important energy source for many organs, especially the heart, kidney and brain. They are utilized by the body with the help of succinyl CoA transferase (SCOT), which is ubiquitously expressed in various organs. Previously, we identified a novel SCOT-t specifically expressed in testicular germ cells and sperm, substituting somatic cell-type SCOT, however the physiological role of SCOT-t had not then been clarified. In the present study, we investigated the effects of ketone bodies, the substrate of SCOT-t, on the motility and acrosome reaction of mouse sperm. D-beta-hydroxybutyrate and acetoacetate both stimulated the motility of sperm as glucose or pyruvate. The glycolysis inhibitor stopped the motility of sperm mediated by glucose but not by D-beta-hydroxybutyrate. In contrast, ketone bodies did not stimulate the activation of the acrosome reaction of sperm, different from the effect of glucose. These results indicate that ketone bodies could be involved in sperm movement but not the acrosome reaction and the SCOT-t enzyme we have identified in sperm mitochondria may have important roles in the activity of sperm, resulting in male infertility when its function is disabled.
3-Hydroxybutyric Acid↗
Diabetes-associated nitration of tyrosine and inactivation of succinyl-CoA:3-oxoacid CoA-transferase.
High levels of reactive species of nitrogen and oxygen in diabetes may cause modifications of proteins. Recently, an increase in protein tyrosine nitration was found in several diabetic tissues. To understand whether protein tyrosine nitration is the cause or the result of the associated diabetic complications, it is essential to identify specific proteins vulnerable to nitration with in vivo models of diabetes. In the present study, we have demonstrated that succinyl-CoA:3-oxoacid CoA-transferase (SCOT; EC 2.8.3.5) is susceptible to tyrosine nitration in hearts from streptozotocin-treated rats. After 4 and 8 wk of streptozotocin administration and diabetes progression, SCOT from rat hearts had a 24% and 39% decrease in catalytic activity, respectively. The decrease in SCOT catalytic activity is accompanied by an accumulation of nitrotyrosine in SCOT protein. SCOT is a mitochondrial matrix protein responsible for ketone body utilization. Ketone bodies provide an alternative source of energy during periods of glucose deficiency. Because diabetes results in profound derangements in myocardial substrate utilization, we suggest that SCOT tyrosine nitration is a contributing factor to this impairment in the diabetic heart.
Animals↗
Nutrient conservation increases with latitude of origin in European Pinus sylvestris populations.
Nutrient availability varies across climatic gradients, yet intraspecific adaptation across such gradients in plant traits related to internal cycling and nutrient resorption remains poorly understood. We examined nutrient resorption among six Scots pine (Pinus sylvestris L.) populations of wide-ranging origin grown under common-garden conditions in Poland. These results were compared with mass-based needle N and P for 195 Scots pine stands throughout the species' European range. At the common site, green needle N (r(2)=0.81, P=0.01) and P (r(2)=0.58, P=0.08) concentration increased with increasing latitude of population origin. Resorption efficiency (the proportion of the leaf nutrient pool resorbed during senescence) of N and P of Scots pine populations increased with the latitude of seed origin (r(2) > or = 0.67, P < or = 0.05). The greater resorption efficiency of more northerly populations led to lower concentrations of N and P in senescent leaves (higher resorption proficiency) than populations originating from low latitudes. The direction of change in these traits indicates potential adaptation of populations from northern, colder habitats to more efficient internal nutrient cycling. For native Scots pine stands, results showed greater nutrient conservation in situ in cold-adapted northern populations, via extended needle longevity (from 2 to 3 years at 50 degrees N to 7 years at 70 degrees N), and greater resorption efficiency and proficiency, with their greater resorption efficiency and proficiency having genotypic roots demonstrated in the common-garden experiment. However, for native Scots pine stands, green needle N decreased with increasing latitude (r(2)=0.83, P=0.0002), and P was stable other than decreasing above 62 degrees N. Hence, the genotypic tendency towards maintenance of higher nutrient concentrations in green foliage and effective nutrient resorption, demonstrated by northern populations in the common garden, did not entirely compensate for presumed nutrient availability limitations along the in situ latitudinal temperature gradient.
Adaptation, Physiological↗
Structure of the mammalian CoA transferase from pig heart.
Ketoacidosis affects patients who are deficient in the enzyme activity of succinyl-CoA:3-ketoacid CoA transferase (SCOT), since SCOT catalyses the activation of acetoacetate in the metabolism of ketone bodies. Thus far, structure/function analysis of the mammalian enzyme has been predicted based on the three-dimensional structure of a CoA transferase determined from an anaerobic bacterium that utilizes its enzyme for glutamate fermentation. To better interpret clinical data, we have determined the structure of a mammalian CoA transferase from pig heart by X-ray crystallography to 2.5 A resolution. Instrumental to the structure determination were selenomethionine substitution and the use of argon during purification and crystallization. Although pig heart SCOT adopts an alpha/beta protein fold, resembling the overall fold of the bacterial CoA transferase, several loops near the active site of pig heart SCOT follow different paths than the corresponding loops in the bacterial enzyme, accounting for differences in substrate specificities. Two missense mutations found associated with SCOT of ketoacidosis patients were mapped to a location in the structure that might disrupt the stabilization of the amino-terminal strand and thereby interfere with the proper folding of the protein into a functional enzyme.
Amino Acid Sequence↗
Neonatal hypoglycaemia in severe succinyl-CoA: 3-oxoacid CoA-transferase deficiency.
Succinyl-CoA: 3-oxoacid CoA-transferase (SCOT) deficiency is an inborn error of ketone body utilization, characterized by intermittent ketoacidotic crises and persistent ketosis. The diagnosis was suspected in a patient who presented with hypoglycaemia, ketoacidosis and coma at 4 days of age. The hypoglycaemic tendency was only observed during the first month of life. A novel macromolecular labelling assay in cultured skin fibroblasts using D-3-hydroxy[3-14C]butyrate supported the diagnosis. Subsequently, 9% residual SCOT activity and undetectable cross-reactive protein were noted in fibroblasts and the patient was found to be homozygous for the G324E SCOT gene mutation. By 7 years of age, recurrent episodes of ketoacidosis superimposed on persistent hyperketonaemia had resulted in over 25 hospitalizations requiring intravenous fluid, glucose and sodium bicarbonate therapy. He has had normal growth but developmental delay and attention deficit-hyperactivity disorder. A continuous intravenous glucose infusion at 38 microlmol (6.8 mg)/kg per min reduced plasma total ketone levels from greater than 1.5 mmol/L to less than 0.5 mmol/L after 48 h. This indicates that patients with SCOT deficiency do not always manifest ketosis with administration of a sufficient amount of carbohydrates, but that even under such conditions hyperketonaemia is difficult to eliminate completely. The presence of hypoglycaemia does not exclude the diagnosis of SCOT deficiency in infancy.
Attention Deficit Disorder with Hyperactivity↗
Food-plant effects on larval performance do not translate into differences in fitness between populations of Panolis flammea (Lepidoptera: Noctuidae).
In the UK, Panolis flammea (Denis & Schiffermüller) is a pest of monocultures of non-native lodgepole pine Pinus contorta Douglas, but not of the indigenous host Scots pine P. sylvestrisL. This difference in population dynamics may be due to the adaptation of P. flammea populations to the phenology, chemical composition and natural enemy complement of lodgepole pine. To ascertain if there was local adaptation of P. flammea populations to lodgepole pine, this study tested for improved performance of both larvae and adults on the host plant species from which they were sourced, compared with their performance on the alternative host plant species. No difference was found in the relative mean performance of populations sourced from Scots pine or lodgepole pine plantations, when fed on Scots or lodgepole pine foliage. Larvae grew faster on Scots pine but this difference did not translate into differences in pupal weight, female body weight or fecundity. Indeed, those insects that had fed on lodgepole pine had a longer lifespan than those that had fed on Scots pine, which, if translated into greater probability of mating or higher fecundity, could contribute to the observed outbreak dynamics in the field. The prediction that the observed outbreak dynamics of P. flammea can be explained by the existence of populations locally adapted to lodgepole pine was not supported. These results cast doubt on the use of larval growth parameters as surrogates of fitness in Lepidoptera.
Adaptation, Physiological↗
Low nucleotide diversity at the pal1 locus in the widely distributed Pinus sylvestris.
Nucleotide polymorphism in Scots pine (Pinus sylvestris) was studied in the gene encoding phenylalanine ammonia-lyase (Pal, EC 4.3.1.5). Scots pine, like many other pine species, has a large current population size. The observed levels of inbreeding depression suggest that Scots pine may have a high mutation rate to deleterious alleles. Many Scots pine markers such as isozymes, RFLPs, and microsatellites are highly variable. These observations suggest that the levels of nucleotide variation should be higher than those in other plant species. A 2,045-bp fragment of the pal1 locus was sequenced from five megagametophytes each from a different individual from each of four populations, from northern and southern Finland, central Russia, and northern Spain. There were 12 segregating sites in the locus. The synonymous site overall nucleotide diversity was only 0.0049. In order to compare pal1 with other pine genes, sequence was obtained from two alleles of 11 other loci (total length 4,606 bp). For these, the synonymous nucleotide diversity was 0.0056. These estimates are lower than those from other plants. This is most likely because of a low mutation rate, as estimated from between-pine species synonymous site divergence. In other respects, Scots pine has the characteristics of a species with a large effective population. There was no linkage disequilibrium even between closely linked sites. This resulted in high haplotype diversity (14 different haplotypes among 20 sequences). This could also give rise to high per locus diversity at the protein level. Divergence between populations in the main range was low, whereas an isolated Spanish population had slightly lower diversity and higher divergence than the remaining populations.
ATP-Binding Cassette Transporters↗
Abnormal activation and inactivation mechanisms of rod transduction in patients with autosomal dominant retinitis pigmentosa and the pro-23-his mutation.
PURPOSE: The leading edge of the rod a-wave in normal human subjects can be fit with a computational model of the activation phase of transduction to provide parameters analogous to those obtained from individual photoreceptors. The authors extend this work to the kinetics of recovery after saturating flashes. METHODS: Electroretinograms were recorded from three patients with autosomal dominant retinitis pigmentosa and the pro-23-his rhodopsin mutation, two patients with rod monochromatism, and five normal subjects. Rod-only a-waves were obtained for a series of flashes ranging from 4.4 to 10.1 ln (1.9 to 4.4 log) scot td-sec. One set of parameters describing the activation process was derived from fits to the a-wave model. A double-flash paradigm was used to study inactivation mechanisms. The first flash was achromatic and varied in intensity (I(f)) from 6.1 to 13.9 ln (2.6 to 6.0 log) scot td-sec. The second flash was a short-wavelength probe held constant at 9.3 ln (4.0 log) scot td-sec. Cone components were elicited with a photopically matched long-wavelength stimulus and were computer subtracted. Recovery at each I(f) was followed by measuring the amplitude to the probe flash at various interstimulus intervals (ISI). The critical time (Tc) before the initiation of rod recovery was determined from the function relating relative rod amplitude to ISI. RESULTS: Recovery from activation was similar in normal subjects and in patients with rod monochromatism. Over a large range of I(f) above rod saturation, Tc increased in proportion to ln I(f). The mean slope of the function relating Tc to I(f) was 2.3 s/ln I(f) when I(f) varied between 11 and 13.9 ln scot td-sec. Patients with retinitis pigmentosa and the pro-23-his rhodopsin mutation had a decrease in the gain of activation. They also had significantly slower than normal recovery after high test flash intensities, such that the slope of the function relating Tc to ln I(f) was 12.1 seconds. CONCLUSION: Available data from other species imply that complete, transient activation of transducin (T saturation) occurs within or below the investigated range of flash intensities. Based on the slope of the delay function (delta Tc/ delta ln I(f)) above 11 ln scot td-sec, the authors hypothesize that the lifetime of activated rhodopsin (R) in normal human rods is approximately 2.3 seconds. In patients with the pro-23-his mutation, the gain of the activation mechanism is reduced and the reaction determining the delta Tc/ delta ln I(f) slope is markedly slowed. The activated species that exhibits this prolonged lifetime could be the mutant rhodopsin itself.
Adolescent↗
From candelas to photoisomerizations in the mouse eye by rhodopsin bleaching in situ and the light-rearing dependence of the major components of the mouse ERG.
To quantify the rate at which light in a ganzfeld produces photoisomerizations in mouse rods in situ, we measured the rate of rhodopsin bleaching in eyes of recently euthanized mice with fully dilated pupils. The amount of rhodopsin declined as a first-order (exponential) function of the duration of the exposure at the luminance of 920 scot cd m(-2): the rate constants of bleaching were 8.3 x 10(-6) and 2.8 x 10(-5) s(-1) (scot cd(-1)m2)(-1) for C57B1/6 and 129P3/J mice, respectively. When the approximately 3-fold difference in effective areas of the pupils of the mice are taken into consideration, the bleaching rates for both strains become essentially the same, 2.6 x 10(-6) fraction rhodopsin (scot Td s)(-1). Assuming 7 x 10(7) rhodopsin molecules per rod, this bleaching rate yields the result that a flash of 1 scot Td s produces 181 photoisomerizations per rod, a value close to that derived from analysis of the collecting area of the rod for axially propagating light. We measured the electroretinograms of mice of the two strains reared under controlled illumination conditions (2 and 100 lux), and compared their properties, using the calibrations to determine the absolute sensitivities of the b-wave and a-waves. The intensity that produces a half-saturating rod b-wave response is 0.3-0.6 photoisomerizations rod(-1), and the amplification constant of the rod a-wave is 5-6 s(-2) photoisomerization(-1), with little dependence on the strain.
Albinism, Ocular↗
Evidence that longer needle retention of spruce and pine populations at high elevations and high latitudes is largely a phenotypic response.
There is abundant evidence that evergreen conifers living at high elevations or at high latitudes have longer-lived needles than trees of the same species living elsewhere. This pattern is likely caused by the influence of low temperature in combination with related factors such as a short growing season and low nutrient availability. Because it is not known to what degree such patterns result from phenotypic versus genotypic variation, we evaluated needle longevity for common-garden-grown lowland populations of European Scots pine (Pinus sylvestris L.) of wide latitudinal origin and Norway spruce (Picea abies L.) of wide elevational origin. Nine-year-old trees of 16 Scots pine populations ranging in origin from 47 degrees to 60 degrees N were studied in Kórnik, Poland (52 degrees N) and 18-year-old trees of 18 Norway spruce populations ranging in origin from 670 to 1235 m elevation in southwestern Poland were studied near Morawina, Poland (51 degrees N, 180 m elevation). There was no tendency in either species for populations from northern or high elevation origins to retain needles longer than other populations. All of the Scots pine populations had between 2.5 to 3.0 needle age cohorts and all of the Norway spruce populations had between 6.4 and 7.2 needle age cohorts. Thus, extended needle retention in Scots pine and Norway spruce populations in low-temperature habitats at high elevations and high latitudes appears to be largely an environmentally regulated phenotypic acclimation.
Journal Article↗
Effects of exogenous gibberellin and auxin on shoot elongation and vegetative bud development in seedlings of Pinus sylvestris and Picea glauca.
The hormonal control of stem unit (foliar appendage and axillary structure, if present, plus subtending internode) number and length was investigated in shoots of Scots pine (Pinus sylvestris L.) and white spruce (Picea glauca (Moench) Voss). Seedlings were treated with six gibberellins (GA1, GA3, GA4, GA5, GA9 and GA20) and two auxins (indole-3-acetic acid (IAA) and naphthaleneacetic acid (NAA)) when either neoformed growth was occurring or the terminal vegetative bud was developing. Hormones were applied by drenching the shoot tip, injecting the stem or spraying the foliage. Combined results for all three application methods indicated that shoot elongation in first-year seedlings (i.e., neoformed growth) was promoted in both species by GA1, GA3, GA4 and, less obviously, by GA9. This promotion was attributable to an increase in length, rather than number, of stem units. However, the number of stem units formed during terminal bud development, as reflected in the number of needles (white spruce) or cataphylls (Scots pine) present on the shoot resulting from the terminal bud, was stimulated by GA1, GA3 and GA4 in both species and by GA9 in Scots pine. The GA-induced increase in the number of preformed stem units was associated with increased bud width in white spruce and increased bud length and resulting shoot length in Scots pine. In contrast, application of IAA or NAA either did not affect or inhibited both neoformed growth and terminal bud stem unit number, depending on the application method and concentration. We conclude that, in the Pinaceae, (1) GA stimulates the activity of both the subapical meristem during neoformed growth and the apical meristem during vegetative bud development, and (2) the early non-hydroxylation pathway, via GA9, is the major route of GA biosynthesis. The role of auxin in the control of stem unit number and length remains to be resolved.
Gibberellins↗