Inheritance of very low serum dopamine-beta-hydroxylase activity.

Serum dopamine-beta-hydroxylas (DBH) activity was measured in blood samples obtained from 841 children ages 6-12, 277 adults subjects, and 114 relatives of children with serum DBH activity of less than 50 units. Approximately 4% of the children and 3% of the adult subjects tested had very low sweum DBH activity (50 units or less). Because these subjects appeared to make up a separate subgroup within the population and because of a striking familial aggregation of subjects with very low enzyme activity, serum DBH activity was measured in blood obtained from members of 22 families of probands with very low serum enzyme activity. The results of sibship and pedigree analyses of the data were compatible with autosomal recessive inheritance of very low serum DBH activity. Unaffected parents of probands had serum DBH activity intermediate between that found in affected individuals and in control population. No significant correlation of serum DBH activity with either systolic or diastolic blood pressure was found in this randomly selected population of children.     

Changes of plasma dopamine-beta-hydroxylase activity and other plasma constituents during the cold pressor test

The effect of the cold pressor test on plasma DBH activity in ten healthy human subjects was investigated. Parallel changes of other plasma constituents were ascertained as well. Plasma DBH activity rose by over ten per cent in six of the sen subjects and declined by 14 per cent or more in two subjects; the correlations of altertions in DBH activity with changes of high molecular weight plasma constituents were high (r=0.565 to 0.902); correlations with blood urea nitrogen and plasma glucose were low (r=0.002 to 0.248). The results suggest that factors other than neuronal DBH release may be important in alterations of plasma DBH activity following $\text{acute}$ stresses produced by the cold pressor test in man.     

Influence of age, sex and hypoxia on plasma dopamine-beta-hydroxylase activity in the rat

Using rats (Wistar strain) of our own breed, we studied dopamine-beta-hydroxylase (E.C. 1.14.17.1) (DBH) activity in the plasma of animals of different ages (in correlation to sex) under normal conditions and after exposure to altitude hypoxia (corresponding to 7000 or 9000 m and lasting 20 min). The enzyme was determined by the method of Kato et al. (1974). We found that the given plasma enzyme activity was significantly higher in females than in males, throughout the whole life-span. In addition, we found that minimum activity was reached on about the 14th and 21st day of postnatal life and again on the 40th day, while maximum activity was recorded at the ages of 5, 30 and 35 days and in adult rats. In adult animals (males and females), exposure to altitude hypoxia was followed by a statistically significant increase in plasma DBH activity, which was much more pronounced in females than in males. In males, 240 min after terminating hypoxia plasma DBH activity had returned to normal, but in females it was still significantly raised; after 48 h, plasma DBH activity in females was identical to the activity before exposure to hypoxia. In rats aged 5 and 35 days, hypoxia evoked a fluctuating response. A decrease in activity immediately after terminating hypoxia was followed at 60 min by a return to normal, but at 240 min there was again a significant decrease. In 21-day-old rats, hypoxia did not induce any significant change in plasma DBH activity (the initial activity level in this group was very low).     

Effect of cold pressor stimulation on plasma norepinephrine, dopamine-beta-hydroxylase, and renin activity

Changes in plasma levels of norepinephrine, dopamine-β-hydroxylase (DβH), and renin activity were observed in nine healthy volunteers during cold pressor stimulation. Increases in mean arterial blood pressure and heart rate during cold stimulation were accompanied by a sharp rise in plasma norepinephrine, while plasma DβH and renin activity showed little or no change. The results indicate that plasma norepinephrine accurately reflects acute activation of the sympathetic nervous system in contrast to plasma DβH and renin activity.     

Reduced dopamine-beta-hydroxylase activity in Alzheimer's disease

The activity of the noradrenergic marker enzyme dopamine-beta-hydroxylase was measured in brains removed postmortem from control patients and patients with Alzheimer''s disease. Enzyme activity was decreased in the frontal and temporal cortices and hippocampus in patients with Alzheimer''s disease, but was within the normal range in patients with depression, multiinfarct dementia, and terminal coma.The decrease in enzyme activity in Alzheimer''s disease may reflect an abnormality of cortical noradrenergic fibres in some patients with the disease.     

Correlation between the dopamine-beta-hydroxylase activity and the level of plasma catecholamines during muscular exercise]

The plasma dopamine-beta-hydroxylase activity was measured in 10 healthy untrained volunteers during a graded physical exercise on a bicycle ergometer. The authors have shown a good correlation between the DbetaH activity and the noradrenaline content in plasma. It can therefore be concluded that the DbetaH activity could be a true measure of the sympathetic activity.     

Segregation and linkage analyses of dopamine-beta-hydroxylase activity.

Dopamine-beta-hydroxylase (DBH) activity in serum was measured by spectrophotometric methods in 95 persons of a large family (HGAR 2), along with 27 polymorphic markers from blood, urine and saliva. The distribution of DBH activity, after appropriate transformation and age adjustment, showed a significantly better fit to a mixture of two normal distributions than a single normal distribution. Pedigree segregation analyses showed evidence of a possible major gene governing low levels of DBH activity, segregating in this family in a recessive fashion. Linkage analyses between that major locus and the 27 polymorphic markers showed no significant lod scores favoring linkage. The highest lod score obtained was 0.81 with Lp at zero recombination fraction. In addition, published data on DBH activity measured by radiochemical assays on 22 families with 161 members were reanalyzed as a quantitative trait, with appropriate correction for ascertainment bias. The results were similar to that of HGAR 2, corroborating the existence of a major locus for DBH activity.     

Family studies of plasma dopamine-beta-hydroxylase thermal stability.

There are large individual variations in the thermal stability of human plasma dopamine-beta-hydroxylase (DBH). These variations are a characteristic of the DBH molecule itself. Individual subjects may be classified as those with thermolabile and those with thermostable plasma DBH. Of 362 randomly selected unrelated children, 8.01%, and of 238 randomly selected unrelated adult subjects, 5.46% had thermolabile plasma DBH. There was not a significant correlation of DBH thermolability with either sex or age on the basis of data from 230 adults and children in 53 randomly selected families. Subjects with thermolabile DBH had basal enzyme activity only about 55% of that in subjects with stable enzyme. There was not a direct relationship between DBH thermolability and the allele DBHL, the presence of which results in very low basal enzyme activity. There was a significant familial aggregation of the trait of DBH thermolability, but there was not a significant correlation of this trait among spouses. Although preliminary pedigree evaluation raised the possibility of monogenic inheritance of the trait of DBH thermolability by an autosomal recessive mechanism, three separate families in which both parents had thermolabile enzyme included offspring with thermostable DBH. All five of these offspring had very low basal plasma DBH and were presumed to be homozygous for the allele DBHL. These observations raised the possibility that the trait of plasma DBH thermolability may be inherited, and that there may be an interaction between the locus or loci responsible for thermal stability and the locus DBH.     

Homospecific activity of serum and tissue dopamine-beta-hydroxylase.

The presence of a circulating eosinopoietic factor was investigated by using the mother-embryo system. Eosinopoiesis was induced in the mother and the response evaluated in the fetal liver. The level of eosinophils in the livers of the fetuses from treated mothers was three times that from untreated mothers. The influence of a humoral factor on the eosinopoiesis in the fetal liver is discussed.     

Plasma catecholamines and dopamine-beta-hydroxylase activity in spontaneously hypertensive rats.

Levels of plasma norepinephrine and total catecholamines in spontaneously hypertensive rats bred from a normotensive Kyoto strain of Wistar rats increase between their 8th to 12th week post utero concomitant with the development of hypertension, but levels of plasma norepinephrine are not significantly different between the spontaneously hypertensive strain, a normotensive Kyoto strain and a N.I.H. strain of Wistar rats at either 8 or 12 weeks of age. Plasma total catecholamine levels in the spontaneously hypertensive strain are significantly higher at 12 weeks of age than those in either control strain, while plasma levels of dopamine-β-hydroxylase show no consistant relationship between the three strains. It, therefore, appears unlikely that increased sympathetic neuronal activity is an etiological factor in this form of hypertension.     

pH-Dependent association-dissociation of high and low activity plasma a-l-fucosidase

Summary Population and family studies have confirmed the existence of a plasma a-l-fucosidase polymorphism in humans and the autosomal recessive inheritance of the low activity trait. The frequency of the latter is estimated at 11%. The low activity individuals or variants can also be distinguished by the fact that their plasma a-l-fucosidase is heat-inactivated at acidic pH. Sucrose gradient centrifugation results indicate the transition of non-variant plasma a-l-fucosidase with a molecular weight of 66,000 at pH 8.4 to an enzyme form with a molecular weight of 193,000 at pH 3.0. The former is thermolabile, the latter thermostable. Interconversion is pH-dependent. It is hypothesized that the non-variant enzyme, a monomer at alkaline pH, changes upon acidification into a trimeric conformation via dimerization. The thermolabile variant a-l-fucosidase monomer is not converted into a trimer, but only partially into a dimer.     

Epidemiology of ADHD in Chilean children and adolescents

ADHD prevalence, associated factors, comorbidity and service use are reported for a sample of 1,558 children and adolescents, belonging to four provinces in Chile. The sample is weighted in each step for selection bias. Psychiatric disorders and impairment are assessed with computerized in-home DISC-IV interviews, and a questionnaire regarding socioeconomic and family variables and service use. Estimates of prevalence rates are obtained by means of STATA 11.0 software, with complex sample design. Multivariate logistic regression is used to determine which factors were the best predictors for mental disorders. Participation rate is 82.4 %. The prevalence of ADHD is 10 %, and the most prevalent subtype is the hyperactive/impulsive, with no gender differences. Both hyperactive/impulsive and combined subtypes are more prevalent in children 4–11 than in adolescents. The most prevalent comorbidities are anxiety disorders and oppositional disorder. Anxiety is the more prevalent comorbid disorder in girls and correlated with a combined subtype. Perception of good family functioning, adolescent age and school dropout have a negative association with ADHD diagnosis, while maltreatment shows a positive correlation. Over 50 % of children and adolescents diagnosed with ADHD have used services in the last year. This is the first comprehensive community study of psychiatric disorders in children and adolescents in a South American country. It yields information for child and adolescent mental health programmes in Chile and contributes to cross-cultural epidemiological research.     

Changes in human plasma catecholamines and dopamine-beta-hydroxylase produced by prostaglandin F2 alpha

Clinical research was conducted into the possible interrelationships between prostaglandin (PG) F2alpha and the human sympathetic nervous system. The study also permitted comparison of the relative sensitivity of 2 indicators of sympatho-adrenal activity: 1) the determination of circulating catecholamines, epinephrine and norepinephrine; and 2) analysis of plasma dopamine-8-hydroxylase activity. Intravenous PGF2alpha infusion was administered to college students 12-18 weeks pregnant to produce abortion; the results were compared to results from nonpregnant controls. Circulating norepinephrine but not plasma epinephrine or dopamine-8-hydroxylase levels were increased in response to the PG. There was no correlation between plasma epinephrine and plasma norepinephrine levels. Plasma dopamine-8-hydroxylase activity was found not to be significantly changed by pregnancy, administration of the analgesic and antiemetic, or the PG infusion. In fact, central venous dopamine-8-hydroxylase activity did not differ significantly from that of arterial blood. The PG did not affect cardiac output or maximal expiratory flow rate. It is suggested that the nausea and diarrhea accompanying PGF2alpha infusion may put stress on the sympathetic nervous activity causing the observed increase in plasma norepinephrine concentration. Since no changes in blood pressure, heart rate, central venous pressure, or cardiac output were observed, it is unlikely that PGF2alpha causes even slight impairment of sympathetic nervous system activity.     

Immunohistochemical evidence for a plasma membrane localization of dopamine-beta-hydroxylase in the mouse neuroblastoma

Dopamine-beta-hydroxylase (D beta H), a glycoprotein enzyme which converts dopamine into noradrenaline, was purified from C1300 mouse neuroblastoma and used to raise antibodies in rabbits. Using an indirect immunofluorescence technique the cellular localization of D beta H in C1300 mouse neuroblastoma was compared with that of the superior cervical ganglion. C1300 neuroblastoma D beta H was found to be predominantly localized in the plasma membrane, in contrast to its intracellular localization in the superior cervical ganglion of A/J mice. At least part of the enzyme was found to be associated with the external side of the plasma membrane.     

Sphingomyelinase activity associated with human plasma low density lipoprotein

Isolated human plasma low density lipoprotein (LDL) was observed to possess sphingomyelinase activity. Accordingly, the formation of ceramide was catalyzed by LDL at 37 degrees C using tertiary liposomes composed of sphingomyelin (mole fraction (x) = 0.2), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (x = 0.7), 1, 2-dimyristoyl-sn-glycero-3-phospho-rac-glycerol (x = 0.1), and either the fluorescent sphingomyelin analog Bodipy-sphingomyelin or [(14)C]sphingomyelin as substrates. However, this activity was not present in either very low density lipoprotein or the high density lipoprotein subfractions HDL(2) and HDL(3). Oxidation of LDL abrogated its sphingomyelinase activity. Aggregation of the liposomes upon incubation with LDL was evident from the light scattering measurements. Microinjection of LDL to the surface of giant liposomes composed of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), N-palmitoyl-d-sphingomyelin (C16:0-sphingomyelin), and Bodipy-sphingomyelin as a fluorescent tracer (0.75:- 0.20:0.05, respectively) revealed the induction of vectorial budding of vesicles, resembling endocytosis.