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H Harms

Publications and source records attributed to H Harms.

At least 37 records · Page 2Linked to original sources
PubMed1998

Serotonin transporter gene variants in alcohol-dependent subjects with dissocial personality disorder.

BACKGROUND: We tested the hypothesis that a functional biallelic repetitive element in the 5' regulatory region of the human serotonin transporter gene (SLC6A4) confers susceptibility to serotonin-related personality traits underlying alcohol dependence with dissocial behavior. METHODS: The association study was focused on 64 alcohol-dependent subjects with a dissocial personality disorder (according to ICD-10) who were derived from 315 German alcohol-dependent subjects. The Tridimensional Personality Questionnaire (TPQ) was applied to assess personality dimensions in 101 alcohol-dependent men, including 39 dissocial alcoholics. RESULTS: Our association analyses revealed a trend towards a higher frequency of the short (S) allele of the SLC6A4 polymorphism in dissocial alcoholics compared to 216 German controls (chi 2 = 2.81, df = 1, p = 0.094). Dissocial alcoholics carrying the S/S genotype exhibited significant lower scores of harm avoidance compared to those lacking it (U-test, p = 0.015). Significantly higher novelty seeking scores were obtained in dissocial alcoholics carrying the S allele relative to those lacking it (U-test, p = 0.021). CONCLUSIONS: Our tentative association findings in dissocial alcoholics suggest that the S allele of the 5' regulatory SLC6A4 polymorphism confers susceptibility to a temperamental profile of high novelty seeking and low harm avoidance that has been postulated to underlie dissocial (type-2) alcoholism according to Cloninger's neurogenetic theory of personality.

Adult↗
PubMed1998

Differentiation of low-grade non-Hodgkin's lymphomas using paraffin sections by image processing.

In a previous study, we were able to demonstrate that the differentiation of low-grade non-Hodgkin's lymphomas (NHLs) using digital image analysis of touch imprints obtained from native tumor tissue is feasible. The availability of touch imprints in routine diagnostics, however, is restricted. Therefore, we extended our studies toward paraffin sections being used as routine material for histological diagnoses. To identify five types of NHL classified according to the Revised European American Lymphoma classification, paraffin sections (n=53) of NHL and 9 reactive lymphoid tissues (RLTs) were scanned with a color-video-based microscope system and analyzed by digital image processing. A reliable division between benign and neoplastic lymphoproliferations was achieved. We were able to identify 78% of RLTs as benign and 94% of NHLs as neoplastic. The average probability of correct identification into the six subgroups was 66%. In detail, 78% of RLTs, 50% of chronic lymphocytic lymphomas and MALT-type lymphomas, 72% of mantle cell lymphomas, and 67% of follicle center cell lymphoma were classified correctly. Although the method of subclassifying or identifying NHLs on the basis of a computer-mediated assay is still not usable in daily practice, we show that a reliable differentiation between reactive and neoplastic lymphoproliferative lesions can be achieved by analysis of paraffin sections with high-resolution image analysis and that it is possible to define nuclear structures by identifying subtypes of NHL.

Diagnosis, Differential↗
PubMed1998

Possible allelic association of a tyrosine hydroxylase polymorphism with vulnerability to alcohol-withdrawal delirium.

Recently, an association has been reported between schizophrenia and a rare allele containing 10-repeats (A10) of a polymorphic tetranucleotide motif in the first intron of the tyrosine hydroxylase (TH) gene. The present association analysis tested the hypothesis that the A10 candidate allele confers vulnerability to alcohol-withdrawal delirium with visual hallucinations. The genotype of the TH tetranucleotide polymorphism was assessed in 204 German controls and 311 German alcohol-dependent subjects, including 63 alcoholics with a history of visual hallucinations during withdrawal delirium. The frequency of the A10 allele was significantly increased in the alcoholics with withdrawal delirium (3.2%) compared with that in the controls (0.5%; Fisher's exact test: P = 0.03, two-tailed; OR (A10+) = 6.85, 95% confidence interval: 1.52-30.79). The possible allelic association suggests that allelic variation at the TH locus mediates vulnerability to alcohol-withdrawal delirium in a small proportion of alcohol-dependent subjects.

Adult↗
PubMed1998

Grazing of Tetrahymena sp. on adhered bacteria in percolated columns monitored by in situ hybridization with fluorescent oligonucleotide probes.

Predation of attached Pseudomonas putida mt2 by the small ciliate Tetrahymena sp. was investigated with a percolated column system. Grazing rates were examined under static and dynamic conditions and were compared to grazing rates in batch systems containing suspended prey. The prey densities were 2 x 10(8) bacteria per ml of pore space and 2 x 10(8) bacteria per ml of suspension, respectively. Postingestion in situ hybridization of bacteria with fluorescent oligonucleotide probes was used to quantify ingestion. During 30 min, a grazing rate of 1,382 +/- 1,029 bacteria individual-1 h-1 was obtained with suspended prey; this was twice the grazing rate observed with attached bacteria under static conditions. Continuous percolation at a flow rate of 73 cm h-1 further decreased the grazing rate to about 25% of the grazing rate observed with suspended prey. A considerable proportion of the protozoans fed on neither suspended bacteria nor attached bacteria. The transport of ciliates through the columns was monitored at the same time that predation was monitored. Less than 20% of the protozoans passed through the columns without being retained. Most of these organisms ingested no bacteria, whereas the retained protozoans grazed more efficiently. Retardation of ciliate transport was greater in columns containing attached bacteria than in bacterium-free columns. We propose that the correlation between grazing activity and retardation of transport is a consequence of the interaction between active predators and attached bacteria.

Animals↗
PubMed1998

Modification of alcohol withdrawal by the A9 allele of the dopamine transporter gene.

OBJECTIVE: Determinants of individual vulnerability to alcohol withdrawal symptoms are largely unknown. Because of the substantial role of monoaminergic transporters in limiting time and space effects of synaptic neurotransmission, the dopamine transporter gene (DAT1; locus symbol: SLC6A3) was studied as a candidate gene possibly related to symptoms of uncomplicated alcohol withdrawal. METHOD: In 48 chronically intoxicated alcoholics (diagnosed according to ICD-10), withdrawal symptoms were examined and the presence of a variable-number tandem repeat in the 3' untranslated region of the DAT1 gene was determined. RESULTS: Withdrawal syndromes were more pronounced in the 22 patients carrying the nine-copy repeat than in the 26 patients without this variant. Multiple regression analysis revealed that 4% of the variance of withdrawal was explained by this genotype, whereas 16% was due to the amount of alcohol the patients reported having consumed in the month before detoxification. CONCLUSIONS: The A9 allele of the dopamine transporter gene is associated with more severe effects of alcohol withdrawal, possibly because of modifications of the brain's capacity to compensate for long-term effects of ethanol on cerebral function.

Adult↗
PubMed1998

Objective nuclear grading for node-negative breast cancer patients: comparison of quasi-3D and 2D image-analysis based on light microscopic images.

In a retrospective investigation for a new image-analytical nuclear grading method, we used 145 routine hematoxylin and eosin-stained, paraffin-embedded tissue sections from node-negative breast carcinomas. Cell fields of primary tumors were scanned in a light microscope in successive focus levels in 1-micron steps for thick sections (> or = 5 microns: quasi-3D analysis) and in one focus position for thin sections (< 5 microns: 2D analysis). After image-segmentation, nuclear features for texture and chromatin distribution were calculated. A binary classification tree was constructed for determination of two mathematically defined classes of high- and low-risk tumor cell nuclei. After fixing a cut-point for the portion of high-risk tumor cell nuclei per patient, it was possible to distinguish two different groups with significantly different relapse rates of 4.2% and 74.5% in quasi-3D analysis and 0.0% and 52.0% in 2D analysis, respectively. Large differences between quasi-3D and 2D analysis were only present in the classification of nonrelapse patients, whereas nearly all patients with relapse had more than 50% high-risk tumor cell nuclei. The results show that the information in thicker tissue sections contains important additive components in the third dimension, with respect to the detection of chromatin structure and distribution. This advantage should be exploited for the development of an objective image-analytical nuclear grading system as a highly significant prognostic marker.

Adult↗
PubMed1998

Frequency of trisomy 20 in nonmalignant bronchial epithelium from lung cancer patients and cancer-free former uranium miners and smokers.

Lung cancer is the leading cause of cancer-related deaths. The development of sensitive screening methods to identify at-risk individuals before emergence of clinical disease would permit early intervention that could decrease this mortality. Our previous studies have shown that cells with trisomy 7 can be detected in bronchial epithelium from cancer-free smokers and former uranium miners. However, the use of more than one molecular marker could increase the chance of identifying at-risk individuals. Trisomy 20, which is found in 43-57% of non-small cell lung cancers, is a candidate marker. The purpose of the current investigation was to determine the percentage of cells with trisomy 20 in persons with a high risk for lung cancer. Bronchial epithelial cells that had been assayed for trisomy 7 were assayed for trisomy 20 by fluorescence in situ hybridization. Trisomy 20 was detected in bronchial epithelial cells from lung cancer patients and from smokers and ex-uranium miners without lung cancer. In some cases, patients who were negative for trisomy 7 exhibited trisomy 20. Consequently, more people with field cancerization were identified using both markers. However, the two markers combined did not appear to stratify the risk for lung cancer.

Adult↗
PubMed1997

Dopamine D4 receptor exon III alleles and variation of novelty seeking in alcoholics.

A dysfunction of dopaminergic neurotansmission has been implicated in alcohol-seeking behavior. Recently, a significant association between the seven-repeat allele (DRD4*7R) of a 16 amino acid motif in the third exon of the dopamine D4 receptor gene (DRD4) and the personality trait of novelty seeking has been reported. Our population-based association study tested the hypothesis that the DRD4*7R variant predisposes to high levels of novelty seeking, which may underlie alcohol-seeking behavior. The genotypes of the expressed DRD4 exon III polymorphism were determined in 197 German controls and 252 German alcohol-dependent males, of whom 92 alcoholics completed the tridimensional personality questionnaire. We found no significant differences in the DRD4*7R frequencies between controls and alcoholics, including two subgroups (56 alcoholics with dissocial personality disorder according to ICD-10 and 89 alcoholics with severe withdrawal symptoms) with a high level of novelty seeking. The novelty-seeking scores did not differ significantly between alcoholics (including both subgroups) carrying long alleles with six or more repeats compared with those lacking long alleles. The present results do not provide evidence that the DRD4*7R allele contributes a common and relevant effect to alcohol-seeking behavior in our sample of alcoholics.

Alcoholism↗
PubMed1997

Allelic association of a dopamine transporter gene polymorphism in alcohol dependence with withdrawal seizures or delirium.

Hereditary factors confer susceptibility to alcohol dependence. Alcohol mediates its reinforcing effects by enhancing dopamine activity in the mesolimbic dopamine system. The role of the dopamine transporter in terminating dopaminergic activity in synaptic neurotransmission suggests that variants of the dopamine transporter gene (DAT1) might contribute to individual differences in vulnerability to addictive behavior. Our population-based association study investigated whether variants of DAT1 confer susceptibility to alcohol dependence in 293 alcoholics and clinically more homogeneous subgroups formed by: positive family history, early age-at-onset, delirium, withdrawal seizures, antisocial tendencies, type 1 and 2 alcoholics. Analyzing a VNTR polymorphism in the 3' untranslated region of DAT1, we found a significantly increased prevalence of the nine-repeat allele in 93 alcoholics displaying withdrawal seizures or delirium, compared with 93 ethnically matched nonalcoholic controls (p = 0.003; OR = 2.44; 95% confidence interval: 1.35-4.43). Our data provide evidence that a major genetic determinant of DAT1 influences vulnerability to severe alcohol withdrawal symptoms.

Adult↗
PubMed1997

Influence of the dopamine D2 receptor (DRD2) genotype on neuroadaptive effects of alcohol and the clinical outcome of alcoholism.

The present study was performed to test the hypotheses that allelic variants at the human dopamine D2 receptor gene locus (DRD2) confer susceptibility to alcoholism or are associated with clinical subtypes of alcoholism. We investigated an A --> G substitution polymorphism in the 3'-untranslated region of exon 8 (E8) of DRD2 with allele frequencies of f(G) = 0.295 - 0.329. No significant association of the DRD2 genotype or allele frequencies with alcoholism was found in an association study including 283 alcoholics and 146 non-alcoholic controls. However, the frequent homozygous E8 A/A genotype with f(AA) = 0.47 - 0.48 was associated with increased anxiety and depression scores in alcoholics during the follow up after clinical detoxification treatment. In addition, E8 A/A was associated with increased suicide attempts and showed a tendency towards more severe withdrawal symptoms, early relapse and reduced responsiveness to the dopaminergic agonist apomorphine. Regression analysis revealed the DRD2 E8 genotype as the only significant factor determining withdrawal severity in female alcoholics. The findings suggest an influence of the DRD2 genotype on the neuropharmacological effects of chronic alcohol exposure and the clinical course of alcoholism.

Adaptation, Physiological↗
PubMed1997

Development and characterization of a whole-cell bioluminescent sensor for bioavailable middle-chain alkanes in contaminated groundwater samples.

A microbial whole-cell biosensor was developed, and its potential to measure water-dissolved concentrations of middle-chain-length alkanes and some related compounds by bioluminescence was characterized. The biosensor strain Escherichia coli DH5 alpha(pGEc74, pJAMA7) carried the regulatory gene alkS from Pseudomonas oleovorans and a transcriptional fusion of PalkB from the same strain with the promoterless luciferase luxAB genes from Vibrio harveyi on two separately introduced plasmids. In standardized assays, the biosensor cells were readily inducible with octane, a typical inducer of the alk system. Light emission after induction periods of more than 15 min correlated well with octane concentration. In well-defined aqueous samples, there was a linear relationship between light output and octane concentrations between 24 and 100 nM. The biosensor responded to middle-chain-length alkanes but not to alicyclic or aromatic compounds. In order to test its applicability for analyzing environmentally relevant samples, the biosensor was used to detect the bioavailable concentration of alkanes in heating oil-contaminated groundwater samples. By the extrapolation of calibrated light output data to low octane concentrations with a hyperbolic function, a total inducer concentration of about 3 nM in octane equivalents was estimated. The whole-cell biosensor tended to underestimate the alkane concentration in the groundwater samples by about 25%, possibly because of the presence of unknown inhibitors. This was corrected for by spiking the samples with a known amount of an octane standard. Biosensor measurements of alkane concentrations were further verified by comparing them with the results of chemical analyses.

Aldehydes↗
PubMed1997

Association analysis of a regulatory variation of the serotonin transporter gene with severe alcohol dependence.

The present study tested the hypothesis that the short, low activity variant of a biallelic polymorphism in the 5' regulatory region of the human serotonin transporter (5-HTT) gene confers susceptibility to severe alcohol dependence marked by severe withdrawal symptoms. Applying a phenotype-genotype strategy, our population-based association analysis included 216 German controls and an extreme sample of 103 severely affected alcoholics who were selected from 315 German alcohol-dependent subjects by a history of alcohol withdrawal seizure or delirium. The frequency of the short allele (S) was significantly increased in the severely affected alcoholics, compared with that in the controls (X2 = 3.87, df = 1, nominal p = 0.049). The post-hoc exploration indicated that this allelic association resulted exclusively from a significant excess of the S/S genotype in the severely affected alcoholics (p = 0.035), suggesting a recessively acting effect. Consistently, we found a weak but significant correlation (p = 0.013) between the frequency of the S/S genotype and severity of withdrawal symptoms (WDS): no WDS [18.3%, odds ratio (OR) = 1.16], vegetative WDS only (21.8%, OR = 1.44), and severe WDS with either withdrawal seizure only or delirium only (25.0%, OR = 1.69), and both withdrawal seizure and delirium (30.8%, OR = 2.30). Further studies are required to test whether the tentative genotype-phenotype relationship occurred by chance or reflects a real genotypic association between a recessively modifying effect of the short variant of the functional 5-HTT promoter polymorphism and alcohol withdrawal vulnerability.

Adult↗
PubMed1996

New method of nuclear grading of tissue sections by means of digital image analysis with prognostic significance for node-negative breast cancer patients.

To optimize treatment of the individual patient with node-negative breast cancer, objective, reproducible, and standardized prognostic criteria are required. A number of factors have been studied in recent years, but until now it has been possible to obtain information about the risk of recurrence only for some patients belonging to subgroups with special characteristics. We report the establishment of an image analysis method for nuclear grading as an attempt to solve this problem. In a retrospective analysis, we used routine hematoxylin and eosinstained paraffin sections from 54 node-negative patients with surgery between 1980 and 1985. Cell scenes of primary tumors were scanned in a light microscope in successive focus positions to obtain three-dimensional information. After automatic image segmentation, nuclear features were calculated as input for a first binary classification tree to differentiate between tumor and nontumor cells. Tumor nuclei from patients with or without relapse were defined as high-risk or low-risk nuclei, respectively, and were separated with a second tree. Feature values of the measured tumor nuclei from each patient were examined with this second tree to analyze whether the majority of nuclei for each patient were classified as high-risk or low-risk nuclei. Correct classification rates in the two binary cell classification trees were 88.0% and 83.8%, respectively. In the learning sample of our study, all patients with a relapse had the majority of nuclei in the high-risk group, most with more than 80%. Therefore, it seems to be possible to develop an image analytical risk profile system for nuclear grading to provide information on individual prognosis.

Algorithms↗
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

Biodegradation of 4-nitroanisole by two Rhodococcus spp.

Two Rhodococcus strains, R. opacus strain AS2 and R. erythropolis strain AS3, that were able to use 4-nitroanisole as the sole source of carbon and energy, were isolated from environmental samples. The first step of the degradation involved the O-demethylation of 4-nitroanisole to 4-nitrophenol which accumulated transiently in the medium during growth. Oxygen uptake experiments indicated the transformation of 4-nitrophenol to 4-nitrocatechol and 1,2,4-trihydroxybenzene prior to ring cleavage and then subsequent mineralization. The nitro group was removed as nitrite, which accumulated in the medium in stoichiometric amounts. In R. opacus strain AS2 small amounts of hydroquinone were produced by a side reaction, but were not further degraded.

Anisoles↗
PubMed1996

Improvement of monitoring of melanocytic skin lesions with the use of a computerized acquisition and surveillance unit with a skin surface microscopic television camera.

BACKGROUND: Photographic documentation of melanocytic skin lesions is important. Storage and retrieval of slides, however, take much time and space. OBJECTIVE: Our purpose was to develop and clinically test a computerized acquisition and surveillance (CAS) unit with a television camera for monitoring including measurements of lesional areas. METHODS: A CAS unit connected with a skin surface microscopic television camera was used for monitoring of melanocytic nevi (MN). The lesional area and the skin surface microscopic appearance (SMA) were analyzed after 10 to 21 months in 54 of 1355 MN. RESULTS: In 19 MN (35.2%), changes were found. In eight cases, changes in size of more or less than 15% were detected; in five cases only the SMA changed. In six cases both characteristics changed. CONCLUSION: In approximately 25% of MN, changes were only detectable in the SMA but not with area measurements. This favors the use of systems such as CAS because only they allow a time-saving comparison of actual and previous images.

Basal Cell Carcinoma↗
PubMed1996

Image analysis detects lineage-specific morphologic markers in leukemic blast cells.

This report outlines the morphologic classification of acute myeloid (AML: French-American-British FAB classification: M1) and lymphoid (ALL) leukemia by automatic image analysis and the correlation to immunologic and cytochemical classification. The investigation was carried out on Romanowsky-Giemsa stained bone marrow (n = 15) and blood smears (n = 10) from 25 patients with primary acute leukemia. The cases had been classified as of myeloid or lymphoid origin by three hematologic centers using immunochemistry or cytochemistry, but the specimens were submitted to the authors' laboratory without the diagnosis. The nuclear and cytoplasmic pattern of the blast cells were analyzed by a high resolution image analysis system and the measured and calculated cell features were sorted by means of a classifier program (CART). The image analysis classification was then compared with the immunophenotypical and cytochemical classification. Blood blast cells showed nuclear features that were significantly correlated to a myeloid or lymphoid immunophenotype. In contrast, bone marrow blast cells displayed overlapping and therefore nondiscriminating nuclear features. However, by generating a learning data set using the immunophenotypes the classifier program found specific cytoplasmic features that eventually permitted a differentiation into myeloid or lymphoid subtypes. In summary, the authors suggest that high resolution image analysis of leukemic blast cells detect nuclear and cytoplasmic features that are associated with the immunophenotype and therefore with the lineage determination of the cell. With this new objective and reproducible approach of morphologic cell analysis, it might not only be possible to classify blast cells with minimal cellular differentiation, but furthermore to discover prognostic features because the remarkable difference in classification quality between blood and bone marrow blast cells reported in this study, might be of biologic relevance and requires further investigation.

Adolescent↗