Biomedical subjects

J Mill

Publications and source records attributed to J Mill.

15 recordsLinked to original sources

PubMed2001

QTL association analysis of the DRD4 exon 3 VNTR polymorphism in a population sample of children screened with a parent rating scale for ADHD symptoms.

Current developments in molecular genetics have led to a rapid increase in research aimed at the identification of genetic variation that influences complex human phenotypes. One phenotype that has aroused a great deal of interest is the behavioral trait hyperactivity and the related clinical disorder attention-deficit hyperactivity disorder (ADHD). The driving force behind the molecular genetic research in this area is the overwhelming evidence from quantitative genetic studies that show high heritablility (h(2) = 0.7-0.9) for the behaviors characterizing the diagnosis of ADHD, whether the disorder is viewed as a categorical entity or a continuous trait. To date, molecular studies have aimed at identifying susceptibility genes for ADHD, defined using operational diagnostic criteria, and have focused on variation within genes that regulate dopamine neurotransmission. Several studies report ADHD to be associated with the 7-repeat allele of a 48 bp repeat polymorphism (DRD4-7) in exon 3 of the dopamine D4 receptor gene (DRD4). In this study, we take a dimensional perspective of ADHD and examine the relationship of this DRD4 polymorphism in a sample of children selected from the general population on the basis of high and low scores on the five ADHD items of the Strengths and Difficulties Questionnaire (SDQ) as rated by their parents. We found a significant relationship between DRD4-7 and high-scoring individuals [chi-square = 8.63; P = 0.003; OR = 2.09 (95% CI 1.24 < OR < 3.54), F-statistic = 7.245; P = 0.008].

Adolescent↗

PubMed2001

Attention deficit hyperactivity disorder (ADHD) and the dopamine D4 receptor gene: evidence of association but no linkage in a UK sample.

Recent studies report association and linkage between attention deficit hyperactivity disorder (ADHD) and the 7-repeat allele of a 48 base-pair repeat in the dopamine D4 receptor gene (DRD4). We examined the frequency of this allele in a sample of probands with DSM-IV ADHD using a case-control design, as well as the transmission disequilibrium test (TDT) and haplotype-based haplotype relative risk (HHRR) in the subset of probands with DNA available from both parents. One hundred and thirty-two ADHD probands were compared with 189 controls (chi(2) = 6.17, 1 df, P = 0.01, OR = 1.73, 95% CI = 1.11--2.71). A total of 85 complete trios were available for within-family tests of association and linkage. Fifty-two heterozygous parents carrying one copy of the 7-repeat were informative for the TDT (29 transmitted vs 23 non-transmitted, chi(2) = 0.69). Analysis of the entire sample of 132 probands using TRANSMIT provided no additional evidence for excess transmission of the 7-repeat allele (58 transmitted vs 54 non-transmitted). HHRR gave similar results. We conclude that the case-control findings are likely to be falsely positive, resulting from genetic stratification. However we can not rule out alternative explanations of low statistical power and gene-environment correlation.

Alleles↗

PubMed2001

Association study of a dopamine transporter polymorphism and attention deficit hyperactivity disorder in UK and Turkish samples.

Molecular genetic studies in attention deficit hyperactivity disorder (ADHD) have focussed on candidate genes within the dopamine system, which is thought to be the main site of action of stimulant drugs, the primary pharmacological treatment of the disorder. Of particular interest are findings with the dopamine transporter gene (DAT1), since stimulant drugs interact directly with the transporter protein. To date, there have been eight published association studies of ADHD with a 480 base-pair allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of the gene, five that support an association and three against. We have analysed the same VNTR marker in a dataset of UK Caucasian children and an independent dataset of Turkish Caucasian children with DSM-IV ADHD, using the transmission disequilibrium test (TDT). Results from the UK (chi(2) = 8.97, P = 0.001, OR = 1.95), but not the Turkish sample (chi(2) = 0.93, P = 0.34) support association and linkage between genetic variation at the DAT1 locus and ADHD. When considered alongside evidence from other published reports, there is only modest evidence for the association, consistent with a very small main effect for the 480-bp allele (chi(2) = 3.45, P = 0.06, OR = 1.15), however we find significant evidence of heterogeneity between the combined dataset (chi(2) = 22.64, df = 8, P = 0.004).

3' Untranslated Regions↗

PubMed1996

[Changes of serum enzymes, lactate and hemoglobin concentrations in the blood of young trotting horses due to training exertion].

Until the age of about 2 years, trotters normally grow up on pasture without any kind of training. In the stud farm Lindenhof (Templin, Germany), however, these first 2 years are used for a special fitness training for the young animals: 2-3 times a week, a group of the yearlings is forced to run a distance of about 1700 m on a track at an average speed of up to 10 m/s. Until now, little was known about changes of blood parameters which may occur during such special exercise. This study therefore investigated the activity of selected serum enzymes (aspartate-amino-transferase (AST), alanine-amino-transferase (ALT), gamma-glutamyl-transferase (gamma-GT), lactic dehydrogenase (LDH), alkaline phosphatase (AP), creatine kinase (CK)) and the variations of hematocrit, hemoglobin, lactate, protein, and urea concentration before and after exercise. Except for activity of AP and CK and concentration of urea, all parameters showed a distinct increase after exercise. In particular, the rise in lactic-acid concentration with values up to 23.08 mmol/l was remarkable, however, none of the parameters reached a pathological level. It is therefore concluded that exercise for young trotters over a medium distance-even at high speed-does not cause any injury of myocardium, skeletal muscles or liver cells.

Animals↗

PubMed1990

Characterization of human cDNA and genomic clones for glial fibrillary acidic protein.

Both a partial cDNA clone and a complete genomic clone have been isolated for human gfa, the gene encoding the major component of astrocyte intermediate filaments, glial fibrillary acidic protein (GFAP). The nucleotide sequence of the entire coding region and 102 bp of the 5' flanking DNA was determined. The mRNA start site was identified by primer extension and probe protection experiments, and a novel in vitro transcription and translation procedure was then used to establish that the first ATG in the mRNA initiates GFAP synthesis. The predicted amino-terminal sequence for human GFAP differs greatly from that previously deduced for mouse GFAP from its gene sequence, despite otherwise high homology. This discrepancy was resolved by determining that the published mouse genomic sequence has an incorrect additional base. The corrected sequence produces strong homology between human and mouse GFAP in their predicted amino acid sequences, and suggests that human and mouse GFAP initiate at homologous positions. The beginning sequence deduced here for both proteins is matched closely by that previously obtained for porcine GFAP by direct sequencing of its amino-terminal end. This supports the protein initiation sites proposed, and also indicates that GFAP is not processed at its amino-terminal end.

Base Sequence↗

PubMed1990

Neural control of glutamine synthetase activity in rat skeletal muscles.

The mechanism of glutamine synthetase induction in rat skeletal muscle after denervation or limb immobilization was investigated. Adult male rats were subjected to midthigh section of the sciatic nerve. At 1, 2, and 5 h and 1, 2, and 7 days after denervation, rats were killed and denervated, and contralateral control soleus and plantaris muscles were excised, weighted, homogenized, and assayed for glutamine synthetase. Glutamine synthetase activity increased approximately twofold 1 h after denervation in both muscles. By 7 days postdenervation enzyme activity had increased to three times the control level in plantaris muscle and to four times the control level in soleus muscle. Increased enzyme activity after nerve section was associated with increased maximum velocity with no change in apparent Michaelis constant. Immunotitration with an antiglutamine synthetase antibody suggested that denervation caused an increase in the number of glutamine synthetase molecules in muscle. However, Northern-blot analysis revealed no increase in the steady-state level of glutamine synthetase mRNA after denervation. A mixing experiment failed to yield evidence for the presence of a soluble factor involved in regulating the activity of glutamine synthetase in denervated muscle. A combination of denervation and dexamethasone injections resulted in additive increases in glutamine synthetase. Thus the mechanism underlying increased glutamine synthetase after denervation appears to be posttranscriptional and is distinct from that of the glucocorticoid-mediated glutamine synthetase induction previously described by us.

Animals↗

PubMed1989

[Anesthesia of horses in the standing position].

Painful interventions can be performed on horse in standing position by means of sedative analgesia, also called standing-position anaesthesia. Combinations of anaesthetics are quite often used, in that context, for the purpose of producing analgetic effects stronger and more reliable than those that would be obtainable from one anaesthetic alone. The following combinations were comparatively tested for their analgetic and sedative effects and their effects upon the organism: Chloralhydrate with Ursonarkon (oxazolidone), Chloralhydrate with Rompun (xylazine), Chloralhydrate with morphine hydrochloride, Chloralhydrate with morphine hydrochloride and Ursonarkon, local anaesthesia in conjunction with sedation by Ursonarkon. 50 experiments were conducted on an experimental group of 10 horses under standardised conditions together with complementary tests on 71 horses under field conditions. The experimental methodology used for assessment of analgetic effects was based on defined electrical and thermic stimuli to enable determination of reactive thresholds. An objective comparison was thus possible between the above variants. Local anaesthesia in combination with complementary sedation proved to meet all demands on standing-position anaesthesia, as it was found to eliminate pain and tactile reflexes. Defence movements have to be expected, whenever preparations are used that attack the central nervous system, since while sensations of pain are suppressed, tactile stimuli may be met with reflex responses via the spinal cord and its intrinsic function.

Analgesia↗

PubMed1988

Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles.

The regulation of glutamine synthetase expression by dexamethasone was studied in rat skeletal muscles. Daily administration of dexamethasone caused striking enhancement of glutamine synthetase activity in plantaris, soleus, and diaphragm muscles. Northern blot analysis revealed that the dexamethasone-mediated increase of glutamine synthetase activity was associated with dramatically increased levels of glutamine synthetase mRNA. Both glutamine synthetase activity and mRNA levels were significantly elevated in plantaris muscle at 0.5 mg.kg-1.day-1 of dexamethasone, a dose that approximates endogenous corticosteroid levels in animals under severe stress. Quantification of changes in glutamine synthetase mRNA on the basis of total mRNA (by oligo dT hybridization) also revealed a major increase in glutamine synthetase mRNA. Dexamethasone was without effect on beta-tubulin mRNA levels, indicating that glutamine synthetase induction is not part of a global response to glucocorticoids. Dexamethasone treatment resulted in only an approximately 15% increase in glutamine synthetase activity in heart; there was no change in glutamine synthetase mRNA level in this tissue. Thus glucocorticoids regulate glutamine synthetase gene expression in rat skeletal muscles.

Animals↗

PubMed1985