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Biomedical subjects

J Erdmann

Publications and source records attributed to J Erdmann.

At least 55 records · Page 3Linked to original sources
PubMed1998

Cloning and characterization of the 5'-flanking region of the human cardiotrophin-1 gene.

To enable the analysis of the regulation of the human cardiotrophin-1 gene expression, the 5'-flanking region of the human cardiotrophin-1 gene was cloned and sequenced. Data bank search revealed several cis- active DNA elements (SP1, CREB, C/EBP, AP1 and AP-2 like and GATA) in the proximal 1.1 kb region. Six nested 5-'terminal deletion mutants from -1091/+39 to -218/+39 were fused to a luciferase reportergene and proved to be functionally active after transfection into COS-7 cells.

Animals↗
PubMed1998

Effects of exposure to altitude on men with coronary artery disease and impaired left ventricular function.

The effects of altitude on coronary patients with impaired left ventricular function are virtually unknown and the question arises whether an exposure to altitude poses a risk to such patients. Twenty-three patients with coronary artery disease (mean age 51 +/- 9 years; group H) with a mean ejection fraction of 39 +/- 6% were compared with 23 normal subjects (mean age 53 +/- 6 years; group N). Both groups underwent a maximal symptom-limited bicycle stress test at 1,000 m and 2 days later at 2,500 m. In both groups, exercise capacity decreased significantly (group H, 1,000 m 162 +/- 28 W, 2,500 m 155 +/- 28 W, p = 0.02; group N, 1,000 m 205 +/- 28 W, 2,500 m 198 +/- 25 W, p = 0.02). Maximal heart rate and blood pressure did not differ between 1,000 and 2,500 m; oxygen saturation at rest and during exercise remained unchanged. At 2,500 m, the test was terminated more often because of dyspnea, but the level of perceived exertion (Borg) was similar to that at 1,000 m. There were no complications or signs of ischemia. Thus, patients with coronary artery disease with impaired left ventricular function without residual ischemia have good tolerance to exposure to altitude. The effects in patients are comparable to those in a group of normal subjects and the risk for an adverse event is not increased.

Adult↗
PubMed1998

Effects of estrogen on the concentration of insulin-like growth factor-I in rat bone matrix.

Insulin-like growth factor-I (IGF-I) plays an important role in bone metabolism, but data on the regulation of IGF-I in bone tissue in vivo are still limited. In the present study, we examined the effects of ovariectomy (ovx) and estrogen replacement on the skeletal concentration of IGF-I in the femur shaft of 6-10 week-old female rats. Ovx had no consistent effect on bone matrix IGF-I concentration regardless of animal age at ovx. In contrast, administration of estradiol in doses that exceeded physiological replacement (50 and 150 nmol/kg per day, subcutaneously) significantly increased the bone matrix IGF-I concentration. These are the first in vivo data which demonstrate that estrogens are capable of increasing the concentration of IGF-I in bone tissue. However, this stimulatory effect appears to be limited to supraphysiological estrogen concentrations.

Animals↗
PubMed1998

Concentration of transforming growth factor beta in human bone tissue: relationship to age, menopause, bone turnover, and bone volume.

Transforming growth factor beta (TGF-beta) is thought to play an important role in bone metabolism, but its relationship to human bone turnover and bone mass has not been examined yet. In this study, we measured the concentration of TGF-beta in 811 samples of male and female bone from four representative sites of the human skeleton and in the supernatants of 72 short-term human bone marrow cultures from the iliac crest. The concentrations of TGF-beta1 and TGF-beta2 in the bone matrix were positively correlated with histomorphometric indices of bone resorption and bone formation and with serum levels of osteocalcin and bone-specific alkaline phosphatase. We also observed a positive association between the release of TGF-beta in the bone marrow cultures and serum osteocalcin. Changes in the rate of cancellous or cortical bone remodeling with age or menopause were accompanied by corresponding changes in skeletal TGF-beta. In contrast, there was no significant relationship between the concentration of TGF-beta and bone volume at any skeletal site. In conclusion, our study supports the hypothesis that TGF-beta plays an important role in human bone remodeling, but fails to demonstrate an association between the skeletal concentration of TGF-beta and human bone mass.

Aging↗
PubMed1997

Human 5-HT5A receptor gene: systematic screening for DNA sequence variation and linkage mapping on chromosome 7q34-q36 using a polymorphism in the 5' untranslated region.

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that mediates a wide range of sensory, motor, and cortical functions by activating multiple 5-HT receptor subtypes. In the present study we performed a systematic mutation scan of the complete coding region of the 5-HT5A receptor to explore its variability in the general population. Investigating 46 unrelated healthy subjects by single-strand conformation analysis no sequence changes of likely functional relevance were observed. The detection of a frequent G-->C substitution at position -19 was used for fine scale linkage mapping of the 5-HT5A gene. Employing a polymerase-chain-reaction based assay we genotyped 7 CEPH families (Centre d'Etude du Polymorphisme Humaine) and mapped the receptor to genetic markers on chromosome 7q34-q36.

Chromosome Mapping↗
PubMed1997

5-HT2A receptor and bipolar affective disorder: association studies in affected patients.

The aim of this study was to investigate the possible involvement of genetic variation in serotonin receptors in the aetiology of bipolar affective disorder. The 5-HT2A receptor gene was systematically screened for genetic variants by single strand conformation polymorphism (SSCP) methods in subjects with bipolar affective disorder. Four polymorphisms (two structural changes, Thr25Asn and His4 M52Tyr, and two silent polymorphisms, 102-T/C and 516-C/T) which had previously been found in patients with schizophrenia and control subjects were detected. No novel polymorphisms were found in patients with bipolar affective disorder. These polymorphisms were genotyped in a sample of 129 patients and 252 controls of German origin and 176 patients and 182 controls of British origin. No strong associations were found between any of these polymorphisms and bipolar affective disorder. Genetic variation at the 5-HT2A receptor gene does not play a major role in the pathogenesis of the disorder.

Alleles↗
PubMed1997

[Speech audiometry with logatomes].

BACKGROUND: Logatomes are nonsense syllables used for analyzing the confusion of phonemes by hearing impaired listeners. They can provide a precise differentiation of phonemic confusions which may be useful in the exact adjustment of programmable hearing aids. METHODS: In this study, two lists of logatomes with 108 three-sound combinations with a structure of consonant-vowel-consonant (c-v-c) and vowel-consonant-vowel (v-c-v) were recorded on a compact disk. Twenty normally hearing adults and 28 patients with a sensorineural hearing loss were tested at a comfortable listening level of about 25 +/- 5 dB above the mean audiometric thresholds at 0,5. 1,0 and 2,0 kHz. An index of reduction of speech perception was calculated. RESULTS: A significant relationship between reduction of logatome perception and pure-tone audiometric thresholds at 1,2,3, and 4 kHz was demonstrated. Moreover, it was possible to distinguish between different groups of hearing impairment. CONCLUSIONS: The logatome test helps to analyze specific effects that hearing loss can have on the recognition of acoustic speech signals. The logatome test may become a valuable addition to speech audiometric tests with further standardization.

Adult↗
PubMed1996

Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia.

Using single strand conformational analysis we screened the complete coding sequence of the serotonin 1F (5-HT1F) receptor gene for the presence of DNA sequence variation in a sample of 137 unrelated individuals including 45 schizophrenic patients, 46 bipolar patients, as well as 46 healthy controls. We detected only three rare sequence variants which are characterized by single base pair substitutions, namely a silent T-->A transversion in the third position of codon 261 (encoding isoleucine), a silent C-->T transition in the third position of codon 176 (encoding histidine), and an C-->T transition in position -78 upstream from the start codon. The lack of significant mutations in patients suffering from schizophrenia and bipolar affective disorder indicates that the 5-HT1F receptor is not commonly involved in the etiology of these diseases.

Base Sequence↗
PubMed1996

Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: identification of two naturally occurring receptor variants and association analysis in schizophrenia.

A statistically significant association between a silent mutation (102T/C) in the serotonin-2A (5-HT2A) receptor gene and schizophrenia has recently been reported in a sample of Japanese patients and healthy controls. This finding suggests that genetic predisposition to schizophrenia may be affected by a functional 5-HT2A receptor variant that is in linkage disequilibrium with 102T/C. In the present study, we have sought to identify genetic variation in the 5-HT2A receptor gene by screening genomic DNA samples from 91 unrelated subjects comprising 45 patients with schizophrenia and 46 healthy controls by using single-strand conformation analysis. We have identified four nucleotide sequence variants. Two sequence changes would result in protein alterations: a substitution of threonine by asparagine at position 25 (Thr25Asn), and a substitution of histidine by tyrosine at position 452 (His452Tyr). In order to test for a possible contribution to the development of schizophrenia, we have determined allele frequencies in extended samples of unrelated patients and healthy controls. The two amino acid substitutions are found with similar frequencies in patients and controls, indicating that the presence of these variants is not causally related to the development of schizophrenia. However, the reported association of the non-coding polymorphism 102T/C with the disease has also been detected in our sample (P=0.041, odds ratio=1.28, 95% confidence interval 1.012-1.623).

Alleles↗
PubMed1996

The human serotonin 7 (5-HT7) receptor gene: genomic organization and systematic mutation screening in schizophrenia and bipolar affective disorder.

In the present study, we evaluated the possible contribution of genetic variation of the serotonin 5-HT7 receptor to the development of schizophrenia and bipolar affective disorder. Cloning and characterization of exon-flanking intronic sequences enabled us to investigate the whole coding region and the exon-intron boundaries of the human 5-HT7 receptor gene. Using single-strand conformational analysis, we screened for presence of DNA sequence variation in a sample of 137 unrelated individuals including 45 schizophrenic and 46 bipolar affective patients, as well as 46 healthy controls. We detected two rare naturally occurring receptor variants (Pro-279-Leu, Thr-92-Lys) and a silent nucleotide substitution (A-->G) at position +1233. The occurrence of the Pro-279-Leu and Thr-92-Lys substitutions was studied in an extended sample of patients (n = 462) and controls (n = 335). The Leu-279 variant was found in similar frequency in all groups, indicating that presence of this variant is not causally related to the development of schizophrenia or bipolar affective disorder. The Lys-92 variant was found in a single individual who suffered from bipolar affective disorder. Investigation of the patient's family revealed independent segregation between the Lys-92 variant and psychiatric illness. Our data suggests that genetic variation of the 5-HT7 receptor does not play a major role in the development of bipolar affective disorder and schizophrenia.

Bipolar Disorder↗
PubMed1995

Systematic screening for mutations in the promoter and the coding region of the 5-HT1A gene.

In the present study we sought to identify genetic variation in the 5-HT1A receptor gene which through alteration of protein function or level of expression might contribute to the genetic predisposition to neuropsychiatric diseases. Genomic DNA samples from 159 unrelated subjects (including 45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette's syndrome, as well as 25 healthy controls) were investigated by single-strand conformation analysis. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as the 5' untranslated region of the 5-HT1A gene. The region upstream to the coding sequence we investigated contains a functional promoter. We found two rare nucleotide sequence variants. Both mutations are located in the coding region of the gene: a coding mutation (A-->G) in nucleotide position 82 which leads to an amino acid exchange (Ile-->Val) in position 28 of the receptor protein and a silent mutation (C-->T) in nucleotide position 549. The occurrence of the Ile-28-Val substitution was studied in an extended sample of patients (n = 352) and controls (n = 210) but was found in similar frequencies in all groups. Thus, this mutation is unlikely to play a significant role in the genetic predisposition to the diseases investigated. In conclusion, our study does not provide evidence that the 5-HT1A gene plays either a major or a minor role in the genetic predisposition to schizophrenia, bipolar affective disorder, or Tourette's syndrome.

Base Sequence↗
PubMed1995

External radiotherapy of pituitary adenomas.

PURPOSE: To evaluate therapeutic outcome and side effects of radiotherapy in pituitary adenomas as sole or combined treatment. METHODS AND MATERIALS: Retrospective analysis of 138 patients (74 male, 64 female) irradiated for pituitary adenoma from 1972 to 1991 was performed. Mean age was 49.7 years (15-80 years). Regular follow-up (in the mean 6.53 +/- 3.99 years) included radiodiagnostical [computed tomography (CT), magnetic resonance imaging (MRI), x-ray], endocrinological, and ophthalmological examinations. Seventy patients suffered from nonfunctional pituitary adenoma, 50 patients suffered from growth-hormone producing adenomas, 11 had prolactinomas, and 7 patients had adrenocorticotropic hormone (ACTH) producing pituitary adenomas. In 99 patients surgery was followed by radiotherapy in case of suspected remaining tumor (invasive growth of the adenoma, assessment of the surgeon, pathologic CT after surgery, persisting hormonal overproduction). Twenty-three patients were treated for recurrence of disease after surgery and 16 patients received radiation as primary treatment. Total doses from 40-60 Gy (mean: 45.5 Gy) were given with single doses of 2 Gy 4 to five times a week. RESULTS: Tumor control was achieved in 131 patients (94.9%). In seven patients, recurrence of disease was diagnosed in the mean 2.9 years (9-98 months) after radiotherapy and salvaged by surgery. A statistically significant dose-response relationship was found in favor of doses > or = 45 Gy. Ninety percent of the patients with hormonally active pituitary adenomas had a benefit from radiotherapy in means of complete termination (38%) or at least reduction (52%) of hormonal overproduction. Partial or complete hypopituitarism after radiotherapy developed, depending on hormonal axis, in 12 (prolactin) to 27% (follicle-stimulating hormone FSH) of patients who had not already had hypopituitarism prior to radiation. Two out of 138 patients suffered reduction of visual acuity, which was, in part, related to radiotherapy. Both therapeutic effects and side effects occurred after a latency period of 3 months up to 9 years. CONCLUSION: We conclude that radiotherapy of pituitary adenomas, using modern treatment planning techniques, is effective and safe. To achieve optimal tumor control, doses of 45-48 Gy (conventionally fractionated) should be applied.

Adenoma↗
PubMed1995

Binding properties of the naturally occurring human 5-HT1A receptor variant with the Ile28Val substitution in the extracellular domain.

The cDNA from a schizophrenic patient heterozygous for a mutation of the 5-HT1A receptor gene was used to clone the variant and wild-type DNA into a eukaryotic expression vector. The mutation was characterized by a base pair substitution (A --> G) at the first position of codon 28, leading to an Ile --> Val amino acid exchange. COS-7 cells were transfected with the cDNA of either the wild type or the variant 5-HT1A receptor. The potencies of the 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT), 5-HT and roxindole, and of the antagonists methiothepin and spiperone in inhibiting specific binding of [3H]8-OH-DPAT of the mutant and wild-type 5-HT1A receptor ligands concentration-dependently inhibited specific [3H]8-OH-DPAT binding to both the wild-type and the variant 5-HT1A receptor. The rank order of potency of the ligands in inhibiting [3H]8-OH-DPAT binding was identical at both receptors and was roxindole > 8-OH-DPAT > 5-HT> methiothepin > spiperone. This rank order is characteristic for 5-HT1A receptors. The negative logarithms of the concentrations required for 50% inhibition (pIC50 values) of the ligands at the mutant 5-HT receptor correlated highly significantly with those at the wildtype receptor (r = 0.995). It is concluded that the pharmacological profile of the mutant 5-HT1A receptor does not differ from that of the wild-type 5-HT1A receptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Lack of genetically determined structural variants of the human serotonin-1E (5-HT1E) receptor protein points to its evolutionary conservation.

Using single strand conformational analysis, we screened the complete coding sequence of the serotonin-1E (5-HT1E) receptor gene for the presence of DNA sequence variation in a sample of 157 unrelated individuals. We detected only a silent C-->T transition at the third position of codon 177. The lack of significant mutations leading to structural variants of the human 5-HT1E receptor protein points to a high evolutionary conservation of this receptor protein.

Base Sequence↗
PubMed1994

Identification of genetic variation in the human serotonin 1D beta receptor gene.

Disturbances of serotonergic pathways have been implicated in a wide variety of neuropsychiatric disorders such as depression, anxiety, migraine, and substance abuse. Genetic variation in genes coding for serotonin receptor proteins might well be involved in the genetic predisposition to these diseases and/or of pharmacogenetic relevance. Genomic samples from 46 unrelated healthy subjects were investigated by single-strand conformation analysis (SSCA) to screen for genetic variation in the human serotonin 1D beta (5-HT1D beta) receptor gene. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as 5' untranslated regions of the 5-HT1D beta gene. Four nucleotide sequence variants were found: a coding mutation in nucleotide position 371 which leads to an amino acid exchange (Phe-->Cys) in position 124 of the receptor protein and three mutations in the 5' flanking region. For all mutations specific PCR-based assays were developed which allow rapid genotyping in populations and families. To our knowledge, the Phe-124-Cys substitution is the first natural occurring molecular variant which has been identified for the 5-HT1D beta receptor so far.

Alleles↗
PubMed1994

Linac radiosurgery in brain metastases.

Brain metastases are usually well-circumscribed and more or less spherical lesions. These conditions meet the criteria for radiosurgery (RS). A pilot study initiated by our group in 1983, demonstrated the effectiveness of Linac-RS in the treatment of solitary brain metastases with low radiosensitivity. A second trial including patients with 1-3 metastases started in 1990. By April 1993, 46 patients had been treated in this series. The radiation doses delivered to the tumour margin ranged from 10 to 25 Gy, and were chosen with respect to size, number and location of the tumours or previous whole brain radiotherapy (WBRT), decreasing mainly with increasing tumour volumes. 34/46 patients had a follow-up of more than 12 weeks. In 7/46 patients the disease progressed rapidly during the first weeks after RS and follow-up examinations were not performed. 5/46 patients had a follow-up of less than 6 weeks and follow-up CT/MR-examinations were not available. 14/46 patients received WBRT before RS. The regularly performed follow-up examinations (clinical status, CT-/MR-examinations in 6 or 12 weekly intervals) revealed tumour progression in 5/34 patients. Permanent cessation of the growth (11/34), tumour shrinkage (18/34) and decrease of surrounding oedema together with clinical amelioration have been observed a few weeks after radiosurgery. The median follow-up was 50 weeks. 14/46 patients died due to generalized progression of their disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗