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Biomedical subjects

B Baumann

Publications and source records attributed to B Baumann.

At least 19 recordsLinked to original sources
PubMed1999

Both AP-1 and Cbfa1-like factors are required for the induction of interstitial collagenase by parathyroid hormone.

PTH is a major regulator of calcium homeostasis by mobilizing calcium through bone resorption. We show that the expression of collagenase-3 (MMP-13), a member of the family of matrix metalloproteinases, required for the cleavage of collagens in the bone, is increased upon PTH injection in mice. A cis-acting element in the collagenase-3 promoter was identified which, together with AP-1, is required for induction by PTH. This element contains CCACA motifs which are required for binding of the 65 kDa osteoblast-specific splice variant of Cbfal. Introduction of mutations in this binding site that interfere with protein interaction also eliminates PTH inducibility and transactivation by Cbfa/ Runt proteins. While DNA binding activity of AP-1 is increased upon PTH treatment, high basal level of Cbfa/Runt binding activity is detectable in untreated cells which is not further increased by PTH, suggesting that AP-1 and Cbfal contribute to transcriptional activation through different mechanisms. In agreement with the critical role of both proteins defined in tissue culture cells, expression of collagenase-3 is reduced in mice lacking c-fos and is completely absent in cbfa1-/-embryos. These data provide the first evidence for a critical role of Cbfal, a major regulator of bone development, in PTH-dependent processes such as bone resorption.

Animals↗
PubMed1999

Tyrosine hydroxylase immunoreactivity in the locus coeruleus is reduced in depressed non-suicidal patients but normal in depressed suicide patients.

Noradrenergic neurons of the locus coeruleus (LC) have been implicated in the neurobiology of depression and suicidal behavior. The current postmortem study determined numbers of noradrenergic neurons by immunostaining the synthesizing enzyme tyrosine hydroxylase in the LC of 12 non-elderly depressed patients with a mood disorder as compared to 12 age- and sex-matched normal controls. Six patients were suicide victims, the other six patients died of natural causes. Non-suicidal patients had fewer neurons immunoreactive for tyrosine hydroxylase (TH-ir) than suicide victims or controls. No difference appeared between the number of TH-ir neurons in suicide patients and controls. Numbers of pigmented LC neurons were equal in patients and controls. The differences of TH-immunoreactivity could neither be attributed to drug influences nor to polarity of depressive disorder (i.e., unipolar/bipolar). Numbers of TH-ir neurons correlated positively with mean doses of tri- or tetracyclic antidepressants. Results of this study suggest a presynaptic noradrenergic deficit of the LC in depressed non-suicidal patients. Indirect evidence is provided that suicide is not related to decreased noradrenergic function and that traditional antidepressants may enhance noradrenergic activity of the LC in depressed patients.

Adult↗
PubMed1999

Unipolar-bipolar dichotomy of mood disorders is supported by noradrenergic brainstem system morphology.

BACKGROUND: The biological basis of unipolar-bipolar dichotomy of mood disorders was investigated in this postmortem study by morphological comparison of the locus coeruleus (LC) as the main source of noradrenergic transmission in the brain. METHODS: Numbers and the rostro-caudal as well as ventro-dorsal distribution of neuromelanin-containing neurones in the LC were determined in brainstem of 12 patients with bipolar disorder (n = 6) or major depression (n = 6), and 12 normal comparison subjects. RESULTS: Bipolar patients had significantly more neurones on both sides of the LC as a whole than patients with major depression. Topographical analysis revealed that this difference was restricted to the rostral two thirds and the dorsal part of the LC, in which bipolar patients showed at least a trend to higher neurone numbers as compared to unipolar patients or to controls. LIMITATIONS: Small case numbers. CONCLUSIONS: Results suggest differences of innervation arising from the LC of bipolar patients as compared to patients with major depression. These first data of brainstem transmitter system morphology in unipolar and bipolar disorder are in line with neuroanatomical studies of other brain regions indicating a biological basis of the unipolar-bipolar dichotomy of mood disorders.

Adult↗
PubMed1999

Reduced volume of limbic system-affiliated basal ganglia in mood disorders: preliminary data from a postmortem study.

Volumes of basal ganglia in postmortem brains of 8 patients with mood disorders and 8 control subjects without neuropsychiatric disorder were determined. Morphometry of serial whole-brain sections under the control of postmortem artifacts revealed reduced volumes of the left nucleus accumbens (-32%, P = 0.01), the right and left external pallidum (-20%, P = 0.04), and the right putamen (-15%, P = 0.04) in the patient group compared with the control group. These results suggest that, in particular, the limbic loop of the basal ganglia involving the nucleus accumbens and the pallidum is affected in mood disorders.

Adult↗
PubMed1999

[TNF-alpha secretion by human macrophage-like cells in response to wear particles and its modification by drugs].

UNLABELLED: Tumour necrosis factor (TNF) is considered to be the initiator protein of particle disease leading to aseptic loosening of endoprostheses. The aim of the present study was to investigate the TNF response of the macrophage-like cells (MLC) to the periprosthetic particles typically found during revision surgery. For this purpose, particles of polyethylene (PE), pure titanium (Ti), chromium (Cr), cobalt (Co), alumina ceramic (Al2O3) and zirconium dioxide (ZrO2) were used. Additionally, the therapeutic effect of non-steroidal and steroidal drugs, biphosphonates and pentoxyfylline on PE particles was investigated with the aim of differentiating drugs with, from those without, a positive effect on aseptic loosening. METHOD: In an established macrophage model (Rader et al. 1999), THP1 cells (human monocytic cell line) were differentiated over a period of five days in the presence of vitamin D3 and GM-CSF in macrophage-like cells (MLC). To obtain a TNF profile of the different materials, 10(6) MLC were incubated with each of a range of different particle concentrations. For drug testing purposes 80 x 10(8) PE particles, which evoked a maximum TNF response, were applied together with increasing drug concentrations in the same manner. The supernatant was then investigated for TNF secretion using ELISA. RESULTS: It was found that the greatest TNF response was provoked by Co and PE particles, and was 25 and 23 times as high, respectively, in comparison with control. The smallest TNF secretion was seen with Al2O3 (4 x control) and ZrO2 (5 x control). At the recommended dose, non-steroidal anti-inflammatory drugs (NSAIDs) produced no decrease in TNF secretion. The biphosphonates, etidronate and ibendronate significantly reduced the TNF response of the PE-stimulated macrophages (by 1/7 and 1/5, respectively). Therapeutic doses of pentoxyfylline also led to a decrease of 1/5 in maximum TNF release. CONCLUSION: Ceramic articulating surfaces are superior to metal/metal or PE/PE matings in terms of the biological effects of their wear particles. At therapeutic doses, NSAIDs have no beneficial effect on the process of aseptic loosening. Certain biphosphonates and pentoxyfylline have a positive effect on aseptic loosening.

Biocompatible Materials↗
PubMed1998

Morphometric studies of the entorhinal cortex in neuropsychiatric patients and controls: clusters of heterotopically displaced lamina II neurons are not indicative of schizophrenia.

Subtle cytoarchitectural abnormalities of the rostral entorhinal cortex have been reported to be characteristic for schizophrenics. A main finding was the heterotopic displacement of clusters of lamina II neurons (which appeared morphologically immature) into layer III. Recent findings suggesting a considerable cytoarchitectural heterogeneity of the normal entorhinal cortex renewed interest in this problem and prompted the question of the extent to which 'aberrantly' located cell clusters are really disease-related. Being blind to the clinical diagnosis, we analyzed quantitatively the amount of entorhinal heterotopias in schizophrenics (n = 31), controls (n = 45) and depressive patients (n = 7). It was revealed that heterotopic cell clusters occurred in schizophrenics and controls with roughly the same frequency (amount of clusters per section). In depressive, there were significantly more heterotopias than in controls (right hemisphere). Our data show that heterotopias are common to the rostral part of the human entorhinal cortex and are not a suitable neuroanatomical marker of schizophrenia.

Adult↗
PubMed1998

Human rod monochromacy: linkage analysis and mapping of a cone photoreceptor expressed candidate gene on chromosome 2q11.

We have performed linkage analysis in eight families with rod monochromacy, an autosomal recessively inherited condition with complete color blindness. Significant linkage was found with markers located at the pericentromeric region of chromosome 2. A maximum lod score of 5.36 was obtained for marker D2S2333 at theta = 0.00. Mapping of meiotic breakpoints localized the disease gene between markers D2S2187 and D2S2229. Homozygosity for a number of subsequent markers indicating identity by descent was found in two families and provides evidence for a further refinement of the locus proximal to D2S373. This defines an interval of approximately 3 cM covering the ACHM2 locus for rod monochromacy. Radiation hybrid mapping of the CNGA3 gene encoding the alpha-subunit of the cGMP gated cation channel in human cone photoreceptors resulted in a maximum lod score of 16.1 with marker D2S2311 combined with a calculated physical distance of 6.19cR10,000. Screening of the CEPH YAC library and subsequent STS mapping indicated the physical order cen-D2S2222-D2S2175-(D2S2187/D2S2311)-qtel ofmarkers on 2q11 and showed that the CNGA3 gene maps most closely to D2S2187 and D2S2311. These data indicate that the CNGA3 gene maps within the critical interval of the ACHM2 locus for rod monochromacy and thus is a candidate gene for this disease.

Chromosome Breakage↗
PubMed1998

Inhibition of nuclear factor kappaB activation attenuates apoptosis resistance in lymphoid cells.

Death-inducing ligands (DILs) such as tumor necrosis factor alpha (TNFalpha) or the cytotoxic drug doxorubicin have been shown to activate a nuclear factor kappaB (NFkappaB)-dependent program that may rescue cells from apoptosis induction. We demonstrate here that TRAIL (TNF-related apoptosis-inducing ligand), a recently identified DIL, also activates NFkappaB in lymphoid cell lines in a kinetic similar to TNFalpha. NFkappaB activity is independent from FADD, caspases, and apoptosis induction. To study the influence of NFkappaB activity on apoptosis mediated by TRAIL, CD95, TNFalpha, or doxorubicin, NFkappaB activation was inhibited using the proteasome inhibitor N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal or transient overexpression of mutant IkappaBalpha. Sensitivity for induction of apoptosis was markedly increased by these treatments in apoptosis sensitive cell lines. Moreover, both in cell lines and in primary leukemia cells that are resistant towards induction of apoptosis by DILs and doxorubicin, antagonization of NFkappaB activity partially restored apoptosis sensitivity. These data suggest that inhibition of NFkappaB activation may provide a molecular approach to increase apoptosis sensitivity in anticancer treatment.

Antibiotics, Antineoplastic↗
PubMed1998

The mutant plasmacytoma cell line S107 allows the identification of distinct pathways leading to NF-kappaB activation.

Studies on the mechanisms of inducible and constitutive activity of NF-kappaB transcription factors have been hampered by the lack of appropriate mutant cell lines. We have analyzed the defect in the murine S107 plasmacytoma cell line, which was previously found to lack both constitutive and inducible NF-kappaB activity. Our analysis shows that these cells bear a specific defect that interferes with NF-kappaB induction by many diverse stimuli, such as lipopolysaccharide, phorbol 12-myristate 13-acetate, UV light, x-rays, and H2O2. This does not however represent a general signal transduction defect, because AP-1 transcription factors are readily induced by the same stimuli. Phosphatase inhibitors such as okadaic acid as well as calyculin A can efficiently induce NF-kappaB in S107 cells via a pathway apparently insensitive to the radical scavenger pyrrolidine dithiocarbamate. Furthermore, MEKK1 a protein kinase supposedly induced by some of the above stimuli, is also capable of activating NF-kappaB. Interestingly, both the potent physiological inducer of NF-kappaB TNFalpha as well as endoplasmic reticulum overload can induce NF-kappaB via a PDTC sensitive pathway. In all cases, DNA-binding NF-kappaB complexes are comprised predominantly of p50-RelA heterodimers, and NF-kappaB activation results in the induction of transiently transfected or resident reporter genes. In summary, these results suggest that the pathways for many NF-kappaB-inducing stimuli converge at a specific junction, and this pivotal step is mutated in the S107 cell line. Yet there are alternative routes bypassing this critical step that also lead to NF-kappaB induction. These routes utilized by tumor necrosis factor alpha and endoplasmic reticulum overload are still intact in this cell line.

Animals↗
PubMed1998

Schizophrenia and anteroventral thalamic nucleus: selective decrease of parvalbumin-immunoreactive thalamocortical projection neurons.

This study was designed to examine possible anatomical changes of thalamocortical circuits in schizophrenics. Previous immunocytochemical studies have shown that parvalbumin, a calcium-binding protein, occurs in thalamocortical projection neurons, but not in GABAergic interneurons in the anteroventral thalamic nucleus (AN). Using parvalbumin-immunocytochemistry we investigated the densities of thalamocortical projection neurons in the AN of schizophrenic cases (n = 12) and controls (n = 14). The densities of all neurons in the AN were estimated by Nissl-staining. The majority of thalamocortical projection neurons in AN were identified by parvalbumin-immunoreaction. Significantly reduced densities of thalamocortical projection neurons were estimated in the right (P = 0.003) and left AN (P = 0.018) in schizophrenic subjects. The densities of all neurons in right and left AN were also diminished in schizophrenics; however, these decreases did not reach statistical significance. The reductions of parvalbumin-positive thalamocortical projection neurons were not correlated with the length of disease, this finding supporting the neurodevelopmental etiology of structural abnormalities in schizophrenia.

Adult↗
PubMed1998

[Qualitative evaluation of brain structure in CT in panic disorders].

This CT study was designed to assess brain morphology in panic disorder with and without agoraphobia. Twenty-one patients and 21 normal control subjects matched for age and sex were investigated. Frontal and parieto-occipital cortex, temporal cortex, lateral ventricles and 3rd ventricle were evaluated by qualitative assessment on a 3-point scale (normal, questionable, abnormal). Patients showed significant bilateral enlargement of cortical cerebrospinal fluid (CSF) spaces (p < 0.01). The rating "abnormal" was given to none (0%) of the normal controls, but to 7 (33.3%) of the patients. Explorative analysis showed that these abnormalities were predominantly located in prefrontal regions. No qualitative differences were seen in the temporal cortex, lateral ventricles or third ventricle. These findings support the hypothesis that alterations in brain morphology are involved in the etiology of panic disorder. The lack of a correlation between CSF enlargement and duration of illness suggests that frontal CSF enlargement is a neurobiological vulnerability marker in panic disorder.

Adult↗
PubMed1998

Nitric oxide synthase-containing neurons in the human hypothalamus: reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics.

The neuroanatomical distribution of nitric oxide synthase-immunoreactive neurons was investigated in post mortem hypothalami of 10 patients suffering from schizophrenia, eight patients with depression and 13 matched control cases. Neuronal nitric oxide synthase containing nerve cells were detected in several hypothalamic nuclei including the medial preoptic region, the ventromedial, infundibular and suprachiasmatic nuclei and the lateral hypothalamus. The vast majority of hypothalamic nitric oxide synthase-immunoreactive neurons was found to be located in the paraventricular nucleus. Both magno and parvocellular paraventricular neurons contained the enzyme. A small subset of immunoreactive parvocellular paraventricular neurons co-expresses corticotropin-releasing hormone. The supraoptic nucleus did not contain nitric oxide synthase-immunoreactive neurons. Cell counts of paraventricular nitric oxide synthase-positive neurons in controls, schizophrenics and depressed patients revealed a statistically significant reduction of cell density in the right paraventricular nucleus of depressed patients and schizophrenics as compared to controls. The total amount of nitric oxide synthase-immunoreactive paraventricular neurons was smaller in depressive and schizophrenic patients than in normal cases. The putative pathophysiologic significance of the reduced expression of paraventricular nitric oxide synthase in depressive patients might be related to the supposed regulatory function of nitric oxide in the release of corticotropin-releasing hormone and arginine-vasopressin and/or oxytocin, which have been reported to be over-expressed in the so-called endogenous psychoses, especially in depression.

Adult↗
PubMed1998

[Quantitative assessment of brain morphology with CT in agoraphobia].

This CT study was designed to assess brain morphology in agoraphobia. 21 patients and 21 normal control subjects matched in age and sex were investigated. Frontal and parietooccipital cortex, temporal cortex, lateral ventricles and third ventricle were evaluated by qualitative assessment on a 3-point scale (normal, questionable, abnormal). Patients showed significant bilateral enlargement of prefrontal cortical cerebrospinal fluid (CSF) spaces (p < .05). The rating "abnormal" was given to none (0%) of the normal controls, but to 6 (28.6%) of the patients in the left hemisphere, and to 4 patients (19%) in the right hemisphere, respectively. No qualitative differences were seen in the temporal cortex, lateral ventricles and third ventricle. These findings support the hypothesis that alterations in brain morphology are involved in the etiology of agoraphobia. The lack of a correlation between CSF enlargement and duration of illness suggests that prefrontal CSF enlargement is a neurobiological vulnerability marker in agoraphobia.

Adult↗
PubMed1998

Validity of DSM-IV attention-deficit/hyperactivity disorder for younger children.

OBJECTIVE: Little is known about the validity of the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in young children. Moreover, the results of the DSM-IV field trials raised concerns that inclusion of the new predominantly hyperactive-impulsive type of ADHD in DSM-IV might increase the likelihood of the diagnosis being given to active but unimpaired preschool and primary school children. METHOD: The validity of DSM-IV criteria for each subtype of ADHD was evaluated in 126 children, aged 4 through 6 years, and 126 matched comparison children. Probands and controls were classified by using structured diagnostic interviews of the parent and a DSM-IV checklist completed by the teacher. RESULTS: Children who met DSM-IV criteria for each subtype of ADHD according to parent and teacher reports differed consistently from controls on a wide range of measures of social and academic impairment, even when other types of psychopathology and other potential confounds were controlled. CONCLUSIONS: When diagnosed by means of a structured diagnostic protocol, all three DSM-IV subtypes of ADHD are valid for 4- through 6-year-old children in the sense of identifying children with lower mean scores on measures of adaptive functioning that are independently associated with ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed1997

Frontal CSF enlargement in panic disorder: a qualitative CT-scan study.

Brain morphology was assessed qualitatively in CT scans of 21 patients with panic disorder and 21 normal control subjects. Patients showed significant bilateral enlargement of frontal cerebrospinal fluid (CSF) spaces. These findings suggest that alterations in brain morphology are involved in the etiology of panic disorder.

Adult↗
PubMed1997

Mutation analysis of the ND6 gene in patients with Lebers hereditary optic neuropathy.

DNA sequence analysis of the gene encoding subunit 6 of the NADH-ubiquinone-oxidoreductase complex (ND6) in human mitochondria was performed in 25 independent patients who suffer from Lebers hereditary optic neuropathy (LHON). In 10 cases the well-known LHON mutation at nucleotide position (np) 14484 was detected. Furthermore, silent substitutions at np14167 and np14527 and missense mutations at np14498, np14564, np14568, and np14582 were found in individual patients. The np14498 and np14568 mutations were found in patients who present a typical clinical picture and course of LHON but lack any of the canonical mtDNA mutations. The np14568 mutation, which replaces a moderately conserved glycine by a serine residue, was observed in a single male patient and subsequently excluded in 175 independent controls. The mutation at np14498, which replaces an evolutionarily highly conserved tyrosine with a cysteine, was found in a multigeneration family with four affected members, the eldest carrying a heteroplasmic mixture of mutated and wildtype mtDNA molecules. None of 170 analyzed control subjects carried this mutation. These findings provide evidence that several allelic ND6 gene mutations may be involved in Lebers hereditary optic neuropathy.

Alleles↗
PubMed1997

Changes in CSF spaces differ in endogenous and neurotic depression. A planimetric CT scan study.

Regional planimetric measurements of internal and external CSF spaces were performed in CT scans of 23 patients with endogenous depression (ICD 9, 296.1) and 28 patients with neurotic depression (ICD 9, 300.4) as compared to 56 control individuals without neuropsychiatric disorder. In female patients with endogenous depression, but not in men, the bilateral upper cortical sulci were widened, especially in the frontal regions, and the third ventricle was enlarged. In contrast, the female neurotic depressed group showed no enlargement of CSF spaces, but a narrowing of the Sylvian fissure and of the basal frontal lobe reaching level of significance in the right fronto-temporal region (P = 0.005). No narrowing of CSF spaces was observed in women with endogenous depression. A discriminant analysis of significantly changed CSF regions resulted in a correct classification in 82.4% of depressed women in either the endogenous or the neurotic group. Determination of divergent types of brain pathology might prove as a useful tool in validating the differential classification of these two main subtypes of affective disorders.

Adult↗