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Biomedical subjects

N Dahmen

Publications and source records attributed to N Dahmen.

At least 37 records · Page 2Linked to original sources
PubMed2000

The HTR1B 861G>C receptor polymorphism among patients suffering from alcoholism, major depression, anxiety disorders and narcolepsy.

The HTR1B receptor gene has been linked to antisocial alcoholism in a Finnish population and an American Indian tribe [Lappalainen et al. , Arch. Gen. Psychiatry, 55 (1998) 989]. Using a candidate gene approach, we genotyped 209 patients with alcoholism, 108 patients with major depression, 32 patients with panic disorder, 50 patients with generalized anxiety disorder, 58 patients with narcolepsy and 74 healthy volunteers for the HTR1B 861G>C polymorphism. There was a higher frequency of the HTR1B 861G alleles among the alcohol-dependent patients as compared to the control subjects (chi(2)=4.02, d.f.=2, P=0.04). However, the association resulted from higher frequencies of the opposite alleles (HTR1B 861G), as originally reported by Lappalainen et al. (1998). Although the association in our study might be due to a type I error, the higher degree of HTR1B allele sharing within both populations could also argue for another alcoholism-relevant gene within the proximity of the HTR1B gene on human chromosome 6.

Adult↗
PubMed2000

[Narcolepsy. An illness in transition].

The signs of narcolepsy have been known since the last century and the tetrad of symptoms was described 50 years ago: excessive sleepiness, cataplexy, sleep paralysis, and hallucinations. Polysomnography typically shows decreased sleep and REM sleep latency, and laboratory testing reveals a high association with the human leucocyte antigens (HLA) DQB1*0602 and DQA1*102. Actual studies suggest disturbances in the orexin (hypocretin) neurotransmitter system. However, the exact pathophysiology is still unclear. In Germany, about 1500 patients diagnosed with narcolepsy are known. The prevalence in Caucasian populations is estimated at 50/100,000. Thus, the number of undiagnosed patients is likely to be high.

Cross-Sectional Studies↗
PubMed2000

Sex differences in allelic frequencies of the 5-HT2C Cys23Ser polymorphism in psychiatric patients and healthy volunteers: findings from an association study.

Polymorphisms in the serotonergic system are believed to play a role in the etiology and treatment of different psychiatric illnesses. The 5-HT2C receptor gene is X-linked, with a frequent mutation at nucleotide 68 leading to a Ser-->Cys transition at amino acid 23. Recent studies have demonstrated an impaired function of 5-HT2C receptors and an increased production of the major noradrenergic metabolite 3-methoxy-4-hydroxyphenylethyleneglycol in the cerebrospinal fluid among the subjects carrying the Ser23 allele (Lappalainen et al., 1999). Biol. Psychiatry 46:821). We genotyped patients with alcohol dependence, panic disorder without agoraphobia, generalized anxiety disorder, narcolepsy and normal healthy volunteers for the 5-HT2C Cys23Ser polymorphism. 5-HT2C Cys23Ser allele frequencies and genotypes did not differ among patients with alcohol dependence, panic disorder, generalized anxiety disorder, narcolepsy and normal healthy volunteers. In an overall analysis, female subjects (n = 173) displayed a higher frequency of 5-HT2C Ser23 alleles as compared to males (n = 298, P = 0.0178). The potential mechanisms of the observed gender difference in allele frequencies, including transmission ratio distortion, are discussed.

Adult↗
PubMed2000

Association study of suicidal behavior and affective disorders with a genetic polymorphism in ABCG1, a positional candidate on chromosome 21q22.3.

The gene that codes for the ABC transporter ABCG1 is located in a chromosomal susceptibility region (21q22.3) for affective disorders. Genetic variations in ABCG1 have been associated with affective disorders in Japanese males. In this study, we investigated the distribution of a G2457A polymorphism in patients with affective disorders, suicide attempters with various psychiatric diagnoses and healthy subjects. We initially found a trend towards a modest association with affective disorders in males (p = 0.046 for allele frequencies and p = 0.046 for AA versus GG). We conducted a replication study with independent patients and controls. There was no association with affective disorders, either in the replication or in the combined group. Furthermore, we found no association with suicidal behavior. These findings do not support the hypothesis that ABCG1 is a susceptibility gene for affective disorders or suicidal behavior.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2000

[Anatomic clinical case. Septic state in a patient with chronic obstructive lung disease].

Invasive aspergillosis is a mycelial infection, associated in 15 to 30% of cases with a malignant hemopathy or with other types of cancers. It also constitutes a complication induced by high dosage corticotherapy or long term antibiotherapy. On the occasion of an autopsy of invasive aspergillosis, we review the anatomo-clinical entities associated with aspergillus, the etiopathogenic factors and the diagnostic difficulties.

Aged↗
PubMed1999

Increased frequency of migraine in narcoleptic patients.

We explored the relationship between narcolepsy and different types of headaches. We interviewed 68 patients with idiopathic narcolepsy for the presence of headache symptoms based on the criteria of the International Headache Society (IHS). Eighty-one percent of the patients reported headaches that warranted an IHS headache diagnosis. Fifty-four percent of the patients (64% women, 35% men) had migraine with all IHS criteria fulfilled.

Adult↗
PubMed1999

Blood ethanol levels and adenylyl cyclase activity in lymphocytes of alcoholic patients.

BACKGROUND: The adenylyl cyclase (AC) signal transduction pathway is a target of acute and chronic ethanol actions. This study examined whether AC activity in lymphocyte membranes of male alcoholic patients correlated with blood concentrations of ethanol. METHODS: Patients (n = 13; mean age: 40 +/- 8 years) were studied on the day of admission (day 0) and 2 days later under detoxification. Moreover, 13 age-matched male healthy controls (mean age 40 +/- 9 years) were included. Lymphocyte membranes were prepared by differential centrifugation whereby blood ethanol was washed out. As a measure of AC activity the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate was determined without (basal activity) and with stimulation of the second messenger system by the guanosine triphosphate (GTP) analogue GTP gamma S (20 mumol/L) via the G-protein or by forskolin (100 mumol/L) acting directly on the AC enzyme. RESULTS: On day 0, when ethanol blood concentrations were 38-100 mmol/L, we found a significant negative correlation between ethanol blood levels and stimulated AC activities. On day 2, the negative correlation with blood ethanol levels of day 0 had disappeared. CONCLUSIONS: The consumption of ethanol affects the AC system in lymphocytes of alcohol-dependent patients by a persistent effect on the cAMP forming enzyme.

Adenosine Triphosphate↗
PubMed1999

[Indications for simultaneous origin of a German and American family with type II hereditary amyloid neuropathy].

The classification of familial amyloid neuropathies (FAP) is traditionally based on clinical and regional aspects. In the last 10 years more than 40 mutations of the transthyretin gene have been found to be responsible for different clinical forms of amyloidosis including familial FAP.FAP II is caused by a mutation on the codon 58 of the transthyretin gene. Only two american kindreds (the Maryland/German and the Ohio family) have previously been reported with FAP II starting in the 3rd or 4th decade by sensory disturbances of the hands typically as a carpal tunnel syndrome. We report on a german family with FAP II from the rhine river area south of Mainz. Four members with typical clinical symptoms showed the histidine 58 mutation like the american families with FAP II. Haplotype analysis showed that all of them were haplotype III like the american patients indicating that the american and german kindreds have a genetic linkage and common familial roots.

Adult↗
PubMed1999

Distribution of clozapine and desmethylclozapine between blood and brain in rats.

Desmethylclozapine is the major metabolite of clozapine in serum. Although the metabolite is pharmacologically active in vitro, the occurrence of desmethylclozapine in brain under steady-state conditions and its role for clinical actions of clozapine are unclear. In this study 20 male Sprague-Dawley rats received five oral doses of clozapine 20 mg/kg at 1.5-h intervals. At 0.5, 1, 2 and 5 h after the last administration, at a time four animals were killed for analysis of clozapine and desmethylclozapine concentrations in serum and brain. The treatment yielded steady-state serum concentrations of clozapine that are considered as therapeutically effective in man. Desmethylclozapine concentrations exceeded those of clozapine at 2-5 h after drug application. In brain, drug concentrations were 15.8-fold higher for clozapine than in serum, but only 2.7-fold higher for desmethylclozapine. The brain clozapine concentrations exceeded those of desmethylclozapine by about 3 times. These data indicate that desmethylclozapine is unlikely to play a role for CNS-mediated effects.

Animals↗
PubMed1999

Rapid cloning of cDNA ends polymerase chain reaction of G-protein-coupled receptor kinase 6: an improved method to determine 5'- and 3'-cDNA ends.

Rapid cloning of 5'- and 3'-cDNA ends polymerase chain reaction (5'-/3'-RACE-PCR) is useful to determine unknown 5'- and 3'-cDNA termini. Even if the method can yield complete cDNA sequences within a couple of days, the RACE procedure bears some characteristic traps and often results in amplification of unspecific PCR-products. Here we used improved 5'- and 3'-RACE-PCR protocols to obtain the complete cDNA sequence of the G-protein-coupled receptor kinase 6 (GRK6) from a rat brain cDNA library. The use of an anchored oligo-(dT)16-V-primer in the cDNA synthesis, the addition of single-sided PCR steps prior to the RACE-PCRs and the optimization of the dA-tailing reaction conditions in 5'-RACE enhanced RACE-PCR efficiency. Taken together, the method is a tool to determine unknown 5' and 3'-cDNA ends and enables the detection of different transcription initiation sites and mRNA splice variants even from small tissue samples like distinct brain regions. The extensive troubleshooting section discusses typical problems of each substep and contains additional references for support protocols.

Animals↗
PubMed1999

Quantitation of GABA transporter 3 (GAT3) mRNA in rat brain by competitive RT-PCR.

Gamma-amino butyric acid is the major inhibitory neurotransmitter in the brain. GABA transporters (GATs) remove GABA from the synaptic cleft. Till now, five distinct GABA transporters have been cloned and termed consecutively GAT1 to GAT4 and vGAT. To study the mechanisms by which tolerance and dependence associated with drugs enhancing GABAergic transmission is brought upon we analysed the mRNA expression levels of GATs in various brain regions under different conditions. In this paper, we describe our protocol for measurement of GAT3 mRNA expression, and its validation through control experiments for the various steps. We performed competitive reverse transcription and polymerase chain reaction (RT-PCR) with a competitor cRNA as internal standard. Different amounts of competitor cRNA were added to total RNA prepared from different tissue samples, reverse-transcribed and PCR amplified. The PCR amplification gave two products: the GAT wild type fragment and the competitor fragment. PCR products were separated by gel electrophoresis and band intensities were determined from which the relative and absolute abundance of GAT3 mRNA was calculated by regression analysis. Validation experiments in our laboratory showed a 6% intra-assay and a 15% inter-assay variability of this method.

Animals↗
PubMed1999

[Endothelial evaluation of corneal transplants by digital imaging].

BACKGROUND: Evaluation of corneal graft endothelium in organ culture comprises judgement of cell area, cell form and cell density by phase contrast microscopy after cell border swelling in hypotonic solution. Up to now, cell density has been determined via counting cells by hand within a fixed frame on polaroid images regarding the magnification factor. It was the purpose of this paper to establish a facilitated and reliable method for endothelial cell count by digital imaging and to compare it with our standard procedure of endothelial cell count by hand. MATERIAL AND METHODS: After cell border swelling in hypotonic solution endothelial images are recorded by a digital camera that is connected to a computer system where the grey scale images are processed into binary images using specialized enhancement and thresholding techniques. A fuzzy logic based computer program was developed in order to differentiate between single and multiple objects, i.e. living and necrotic cells. This digital imaging system determines endothelial cell density automatically and offers the possibility to correct the data in any case of misinterpretation. Twenty corneal grafts were evaluated with this system by two experienced investigators and the results were compared with endothelial cell count by hand. RESULTS: Using the new system, intra- and interindividual variability of endothelial cell count was statistically significantly lower compared with evaluation by hand. Furthermore, less time for evaluation and documentation was necessary. CONCLUSIONS: In a reduced period of time endothelial cell density of corneal grafts in organ culture can be determined reliably and reproducibly with the new digital imaging system if the possibility of data correction is used in case of misinterpretation. In the future, the necessity of corrections should be reduced and the use of multiple fixed frames should further improve quality control of corneal grafts.

Cell Count↗
PubMed1999

Chronic oral haloperidol and clozapine in rats: A behavioral evaluation.

The present study evaluated chronic oral treatment of rats with haloperidol or clozapine. Drugs were given in the drinking water for a 23-day period. Rat behavior was analyzed once a week in an open field. Rats ingested either 1.7 mg/kg haloperidol or 40 mg/kg clozapine daily. Blood serum analysis revealed concentrations of 6 ng/ml for haloperidol and 22 ng/ml for clozapine at the end of the treatment. Haloperidol decreased overall activity from the onset of treatment. Clozapine showed similar effects only on the last test day. Control animals showed a slight habituation in exploration-related parameters. In conclusion, these results indicate that oral drug administration through the drinking water is a suitable mode of noninvasive chronic treatment that led to sufficiently high drug levels to induce specific pharmacological effects in rats.

Administration, Oral↗
PubMed1998

Electrophysiological brain stem investigations in idiopathic narcolepsy.

Narcolepsy is associated with various rapid eye movement (REM) sleep abnormalities. Distinct brain stem areas seem to play a prominent role in REM sleep regulation. Recent magnetic resonance imaging (MRI) studies have led to conflicting findings concerning the presence of structural brain stem lesions in patients with idiopathic narcoleptic syndrome. However, multimodal electrophysiological brain stem investigations may reveal functional brain stem abnormalities even in the absence of MRI abnormality. Therefore we investigated brain stem function in 12 idiopathic narcoleptic patients by systematically studying tegmental brain stem pathways. All of the patients met the diagnostic criteria of the International Classification of Sleep Disorders, with typical changes in polysomnography and the multiple sleep latency test. Electrophysiological investigations comprised masseter reflex, blink reflex, masseter inhibitory reflex, early auditory evoked potentials and electrooculography with vestibular testing. In no patient were electrophysiological brain stem abnormalities observed. Our findings do not support the existence of a relevant brain stem lesion in narcoleptic patients with normal neurological status.

Adult↗
PubMed1998

Chronical haloperidol and clozapine treatment in rats: differential RNA display analysis, behavioral studies and serum level determination.

1. Adult, female rats were treated orally for 23 days with 1.6 mg/kg haloperidol or 36 mg/kg clozapine per day, to study chronic effects of the two neuroleptics. 2. At five time points during the neuroleptic treatment, animal behavior was recorded in an open field and locomotive activity was analysed. At the end of the experiment, rats were decapitated, blood samples were collected and serum concentrations of haloperidol and clozapine were determined by a radioreceptor or HPLC assay, respectively. RNA was isolated from each brain, without cerebellum, and subjected to differential RNA display. 3. Mean serum concentrations were 8 ng/ml for haloperidol and 21 ng/ml for clozapine. Analysis of open field behavior showed that haloperidol and clozapine decreased the total distance moved and the velocity as measures of the overall activity, whereas the number of rearings and the number of entries into the center, reflecting risk assessment behavior, were differentially affected. Three neuroleptic-regulated gene fragment bands were identified in differential RNA display experiments. Two gene fragments of 281 bp and 266 bp were sequenced. 4. We conclude that our study design that used behavioral, pharmacokinetic and molecular analysis increase the likelihood of finding relevant molecular events underlying the pharmacotherapeutic effects of neuroleptics in animal models.

Animals↗
PubMed1998

Activity of the adenylyl cyclase in lymphocytes of male alcoholic patients is state dependent.

A decreased basal and/or stimulated activity of the G-protein/adenylyl cyclase (AC) system in peripheral blood cells has been proposed to represent a trait marker for alcoholism. However, AC activity may underlie state-dependent changes, which may impair a proper interpretation of AC activity measurements. Our study examined systematically the AC activity in peripheral lymphocytes of 73 male alcohol-dependent patients (according to DSM-IV criteria) at three different time points of measurement during the clinical course of detoxification (day 0 = at admission, while still ethanol-affected; day 2 = at the presumed peak of withdrawal symptoms; day E = after detoxification). Basal and stimulated (with GTPgammaS and forskolin) AC activities were measured. AC activities were compared to those of a control group of 44 healthy male age-matched volunteers. As our main finding, we detected a significant decrease in AC activity from day 0 to day 2 (during withdrawal), with lowered AC activities in a vast majority of patients. This effect resolved after detoxification, as AC activities showed a significant increase from day 2 to E. No significant difference was detected between day 0 and E in AC activities of the patients. Compared with controls, AC activities in patients were significantly lower at day 2, but not at day 0 and E. Taken together, our results indicate rapid and marked state-dependent changes of AC activities in alcohol-dependent patients during the course of detoxification. For an adequate interpretation of AC activities in alcoholic patients, their clinical status must be taken into consideration.

Adenylyl Cyclases↗