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Biomedical subjects

S Kaiser

Publications and source records attributed to S Kaiser.

At least 19 recordsLinked to original sources

[A 56-year-old female patient with Raynaud's syndrome, increased liver enzymes and neuropsychiatric symptoms].

CASE HISTORY: A 56-year-old woman presented with increased liver enzymes (GPT, GOT), arthralgias, Raynaud's syndrome and disturbance of sleep and concentration. FINDINGS AND DIAGNOSIS: Serology and liver biopsy indicated chronic hepatitis C infection (HCV) and viral-induced liver cirrhosis with unremarkable liver synthesizing parameters. An HCV-triggered cryoglobinemia was excluded, but high elevated antinuclear antibodies (ANA) and anti-RNP autoantibodies, typical serological parameters of mixed tissue collagenous (Sharp}s disease), were detectable. Magnetic resonance spectroscopy (H-MRS) was performed to differentiate between cerebral vasculitis and mild hepatic encephalopathy. This detected abnormal pattern of cerebral metabolites (myo-inositol and choline), is specific for HE. TREATMENT AND COURSE: After onset of an antiviral therapy (terferon/ribavirin), low protein diet with supplementation of l-ornithine-l-aspartate the arthralgia and neuropsychiatric symptoms rapidly improved and HCV-RNA PCR became negative. Unfortunately, after cessation of antiviral treatment the patient had a relapse of HCV with a worsening of the arthralgia and the Raynaud symptoms (HCV-triggered Sharp}s disease). CONCLUSION: Even in patients with mildly abnormal liver function and liver cirrhosis it is important to consider (mild) hepatic encephalopathy if neuropsychiatric symptoms occur.

Alanine Transaminase↗

Pergolide as adjuvant therapy to amisulpride in the treatment of negative and depressive symptoms in schizophrenia.

Negative and cognitive symptoms of schizophrenia are associated with a hypodopaminergic state in the frontal cortex and do not respond to neuroleptics equally well as positive symptoms. Therefore pharmacological strategies, which increase dopamine metabolism in the mesocortical pathways, may prove beneficial to ameliorate these symptoms. We report on a case of a patient with paranoid schizophrenia, who still presented negative and depressive symptoms during treatment with amisulpride for more than 6 weeks. We prescribed pergolide (a mixed D1/D2 agonist) as adjuvant therapy to treat these symptoms. The patient showed an improvement of global psychopathology, decrease of negative and depressive symptoms, while no changes in positive symptoms nor EPS were present. For this patient, the adjuvant therapy of pergolide to amisulpride constituted a valid pharmacological approach to treat negative and depressive symptoms of schizophrenia, without increasing positive symptoms.

Adult↗

Mesenchymal stem cells maintain TGF-beta-mediated chondrogenic phenotype in alginate bead culture.

This article addresses the stability of chondrogenic phenotype and the transdifferentiation potential of bone marrow-derived mesenchymal stem cells (MSCs) at distinct stages of differentiation. Differentiated MSCs were expected to maintain cartilage-like gene expression pattern in the absence of any chondrogenic growth factor or in the presence of osteogenic signals. MSCs encapsulated in alginate beads were treated with transforming growth factor (TGF)-beta 3 for 3, 6, or 14 days and then cultured in absence of TGF-beta for the remainder of the 2-week culture period. Additionally, cells were cultured in osteogenic medium after TGF-beta-mediated chondroinduction. Gene expression of col2a1, aggrecan, COMP, alkaline phosphatase (AP), and correlating protein synthesis was analyzed. After short-term stimulation with TGF-beta, MSCs maintained a chondrogenic phenotype. Chondrogenic gene expression and protein synthesis directly correlated with the extent of stimulation time and the concentration of TGF-beta. Pretreatment with TGF-beta could prevent AP mRNA expression of encapsulated MSCs. TGF- beta stimulation within the first 3 days of culture seems to be crucial for the expression of a chondrogenic phenotype. Fully differentiated and encapsulated MSCs are not able to transdifferentiate into osteoblasts. These findings give rise to a better understanding of the behavior of cartilage grafts affected by local factors of osteochondral transplantation sites in vivo.

Adult↗

Perforin-independent rejection of transplanted human stem cells.

The NOD/SCID mouse model is one of the most established model systems for the analysis of human stem cells in vivo. The lack of mature B and T cells renders NOD/SCID mice susceptible to transplantable human stem and progenitor cells. One remaining functional component of the immune system in NOD/SCID mice is natural killer (NK) cells. We rationalized that by eliminating NK cell-mediated cytotoxicity in this model system engraftment of human haematopoietic stem cells could be improved. Thus perforin-deficient NOD/SCID mice (PNOD/SCID) were generated, which display a complete lack of NK cell-mediated cytotoxicity. To test the engraftment potential of human stem cells in PNOD/SCID mice, we compared the repopulating potential of human haematopoietic stem cells in these mice with the repopulating potential in NOD/SCID mice. Upon injection with varying numbers of mononuclear cells from human cord blood, the number of engrafted PNOD/SCID mice was lower (34.8%) than the number of engrafted NOD/SCID mice (64.7%). Similarly, injection of purified CD34(+) human cord blood cells led to engraftment in 32.3% PNOD/SCID versus 60% in NOD/SCID mice. Surprisingly, these results show that the inactivation of cytotoxic activity of NK cells in PNOD/SCID mice did not result in better engraftment with human haematopoietic stem cells. A potential reason for this observation could be that compensatory activation of NK cells in PNOD/SCID mice induces high levels of soluble factors resulting in an environment unfavourable for human stem cell engraftment.

Animals↗

[Detection of subclinical and overt hepatic encephalopathy and treatment control after L-ornithine-L-aspartate medication by magnetic resonance spectroscopy ((1)H-MRS)].

Hepatic encephalopathy (HE) is a common problem in liver cirrhosis and is associated with typical changes of cerebral metabolite pattern observed by proton magnetic resonance spectroscopy (MRS). In HE, a reduction of the cerebral myo-inositol (mI) and choline (Cho) and an increase of glutamine/glutamate (Glx) can typically be detected with this method. In the present study MRS was used to assess prospectively specific parameters of cerebral metabolism before and after 6 days of treatment with a low-protein diet and with L-ornithine-L-aspartate (LOLA). 6 patients with liver cirrhosis were included in this pilot study. According to standardized neuropsychological tests overt HE or subclinical HE was detected in all patients. All patients received a low-protein diet (< 60 g/d) and were treated additionally with LOLA (20 g QD i. v.). MRS examinations were done before and after 6 days of treatment and the results were compared with those of healthy volunteers. Before treatment mI/Cr ratios in the grey matter were reduced significantly in cirrhotic patients as compared to healthy volunteers (0.30 +/- 0.22 vs. 0.68 +/- 0.11; P = 0.028). In addition, patients showed a (non-significant) reduction of the Cho/Cr-ratio (0.19 +/- 0.03 vs. 0.25 +/- 0.02; P = 0.17) and an elevated Glx/Cr-ratio (1.84 +/- 0.63 vs. 1.29 +/- 0.31; P = 0.05). After 6 days of treatment a significant increase of the Cho/Cr ratio (0.23 +/- 0.03 vs. 0.19 +/- 0.03; P = 0.028) was detectable and 5 of the 6 patients showed a (not significant) decrease of the elevated Glx/Cr ratios. After cessation of treatment an improvement in neuropsychological tests as shown by number-connection testing (P = 0.046) as well as a decrease of elevated pre-treatment ammonia blood levels were noted. These findings, however, did not correlate with the Child-Pugh classification or evidence of clinical/subclinical HE. Using (1)H-MRS it is possible to observe a specific pattern of cerebral metabolites in patients with overt and subclinical HE. In this pilot study a fast change of cerebral metabolite pattern after specific therapy of HE with LOLA was detected. Therefore, future studies with larger patient groups are needed to establish (1)H-MRS as an objective method for detection and treatment control in overt and subclinical HE, especially when compared to commonly used parameters such as ammonia levels or standardized neuropsychological tests.

Adult↗

[Executive control functions and neuropsychiatric disorders -- perspectives for research und clinical practice].

Executive control functions are higher cognitive functions for complex goal-oriented behavior in situations where routine mechanisms are not available or inappropriate. In clinical practice executive dysfunction presents with deficits in cognitive function as well as social behavior and drive. Executive control functions rely on intact networks involving prefrontal cortex and subcortical structures, which can be modulated by monoaminergic neurotransmitters. Deficits of executive control have been described in a variety of neuropsychiatric disorders. We present a review of the findings with a focus on movement disorders, schizophrenia and affective disorders. We emphasize similarities between these disorders regarding the pathophysiology of fronto-subcortical networks. Based on these similarities, principles of pharmacological and rehabilitative strategies can be applied to the treatment of executive deficits in a variety of neuropsychiatric disorders without being specific for one disease. Since executive dysfunction is highly relevant to prognosis, controlled trials of these treatments are urgently needed.

Basal Ganglia Diseases↗

VEMH - Virtual Euro-Mediterranean Hospital for Global Healthcare.

The Virtual Euro-Mediterranean Hospital (VEMH) aims to facilitate the interconnection of various medical services through real integration. VEMH will provide an integrated satellite-terrestrial platform and realize telemedical services such as e-learning, real-time telemedicine and medical assistance and offer individual grants to young medical doctors. The methodologies of the VEMH are medical-need-oriented instead of technology-oriented. VEMH will provide for medical professionals in the whole Euro-Mediterranean area access to the required quality of medical service. For the successful deployment of the services of the VEMH GRID technologies have to be implemented especially for evidence-based medicine. A Metagrid Service Engine implements an additional software layer between proprietary GRID engines and the different applications. The use of mobile code is envisioned in future GRIDs which allows service creation and deployment on arbitrary nodes of a GRID. Dynamic Grid structures become an important point for the use of mobile code.

Computer Systems↗

Appendicitis in children--impact of US and CT on the negative appendectomy rate.

BACKGROUND/PURPOSE: Ultrasonography (US) and computed tomography (CT) have proved useful for the evaluation of suspected appendicitis and were introduced as diagnostic tools at our institution about ten and five years ago, respectively. The aim of this study was to evaluate how the negative appendectomy and perforation rates have changed with increased use of US and CT. METHODS: The medical records of 600 children who underwent appendectomy during years 1991, 1994, 1997, and 2000 were reviewed. Perforation in perforated appendicitis was considered to have occurred after admission if the time interval between the first health professional contact and surgery exceeded 12 hours. RESULTS: The total number of appendectomies during the years 1991, 1994, 1997, and 2000 was 406, 334, 407, and 397, respectively. The negative appendectomy rate for the same years was 23%, 8.7%, 8.0%, and 4.0%, respectively. The overall rate of perforations and the perforation rate after admission was 32% and 12%, 34% and 7.3%, 34% and 13%, and 29% and 2.1%, respectively. The rate of patients who underwent US and CT during each period was 1.0% and 0.0%, 41% and 0.0%, 91% and 21% and 98% and 59%, respectively. CONCLUSIONS: The negative appendectomy rate has been substantially reduced after the introduction of both US and CT. The rate of perforation after admission has not increased.

Adolescent↗

Lack of telomerase activity in human mesenchymal stem cells.

Telomerase activity and telomere maintenance have been associated with immortality in tumor and embryonic stem cells. Whereas most normal somatic cells are telomerase negative, low levels of this enzyme have been found in adult stem cells from the skin, gut and the hematopoietic system. Here, we show that telomerase activity is not detectable in human mesenchymal stem cells (hMSCs), which have the phenotype SH2+, SH3+, SH4+, CD29+, CD44+, CD14-, CD34- and CD45-, and have the capacity to differentiate into adipocytes, chondrocytes and osteoblasts. These data suggest that hMSCs have a different telomere biology compared to other adult stem cells. Alternatively, true mesenchymal stem cells might be a very rare subpopulation that have a detection level that is below the sensitivity of the TRAP assay.

Antigens, CD↗

Early social stress in male Guinea-pigs changes social behaviour, and autonomic and neuroendocrine functions.

The present study was undertaken to investigate the effects of pre- and early postnatal social stress on the functioning of hormonal, autonomic and behavioural systems, by studying the distribution of sex hormone receptors in limbic brain systems. Dams had either lived in groups with a constant composition (= stable social environment) or in groups with changing compositions, i.e. every third day, two females from different groups were exchanged (= unstable social environment). The subjects were male offspring of dams who had either lived in a stable social environment during pregnancy and lactation (= control males) or in an unstable social environment during this period of life (= early stressed males). From days 20-80, the spontaneous behaviour of control males and early stressed males was recorded in their home cages. Five control males and five early stressed males were killed at 75 days, and five control males and five early stressed males at 120 days. Blood samples were taken to determine serum concentrations of cortisol, testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulphate and oestrogen. The adrenals were prepared to determine tyrosine hydroxylase activities and the brains were used to investigate the distribution of sex-hormone receptors in specific hypothalamic and hippocampal brain areas. Early stressed males showed a behavioural infantilization that was accompanied by significantly decreased adrenal tyrosine hydroxylase activities and dehydroepiandrosterone levels. Furthermore, early stressed males showed a down-regulation of androgen receptors in the medial preoptic area and the nucleus arcuatus of the hypothalamus, as well as of oestrogen receptor alpha in the hippocampus compared to control males. Thus, the present study provides clear evidence that early social stress induces changes in endocrine, autonomic and limbic brain function, which is mirrored by changes in male social behaviour.

Animals↗

Human stoned B interacts with AP-2 and synaptotagmin and facilitates clathrin-coated vesicle uncoating.

Synaptic vesicle biogenesis involves the recycling of synaptic vesicle components by clathrin-mediated endocytosis from the presynaptic membrane. stoned B, a protein encoded by the stoned locus in Drosophila melanogaster has been shown to regulate vesicle recycling by interacting with synaptotagmin. We report here the identification and characterization of a human homolog of stoned B (hStnB). Human stoned B is a brain-specific protein which co-enriches with other endocytic proteins such as AP-2 in a crude synaptic vesicle fraction and at nerve terminals. A domain with homology to the medium chain of adaptor complexes binds directly to both AP-2 and synaptotagmin and competes with AP-2 for the same binding site within synaptotagmin. Finally we show that the mu 2 homology domain of hStnB stimulates the uncoating of both clathrin and AP-2 adaptors from clathrin-coated vesicles. We hypothesize that hStnB regulates synaptic vesicle recycling by facilitating vesicle uncoating.

Adaptor Proteins, Vesicular Transport↗

Social stress during pregnancy and lactation affects in guinea pigs the male offsprings' endocrine status and infantilizes their behaviour.

This study investigated the influence of the social environment during pregnancy and lactation on the male offsprings' endocrine parameters and behaviour in guinea pigs. The subjects studied were sons whose mothers had either lived in a stable social environment during pregnancy and lactation or in an unstable social environment during this period of life. The stable social environment was made by keeping the group composition (one male, five females) constant; in the unstable social environment situation every third day, two females from different groups were exchanged. After weaning, seven groups of sons, whose mothers had lived in an unstable social environment and seven groups of sons, whose mothers had lived in a stable social environment, consisting of two males each, were established. From their 20th through their 100th day of age the spontaneous behaviour of the males was recorded in their home cages. On the endocrine level, cortisol- and testosterone-concentrations in serum as well as adrenal tyrosine hydroxylase activities were determined. Sons, whose mothers had lived in an unstable social environment, showed significantly higher amounts of resting with bodily contact than sons, whose mothers had lived in a stable social environment. Additionally, they displayed this behaviour to an older age than the latter sons. Further on, sons, whose mothers had lived in an unstable social environment, displayed significantly higher frequencies of courtship behaviour than sons, whose mothers had lived in a stable social environment, which was integrated into play behaviour. These behavioural data point to an infantilization of sons, whose mothers had lived in an unstable social environment. The behavioural patterns corresponded with a delayed development of the hypothalamo-pituitary-adrenocortical-axis and a lower activity of the sympathetic-adrenomedullary-system compared to sons whose mothers had lived in a stable social environment. Testosterone did not differ between both categories of males. Thus, the instability of the social environment during pregnancy and lactation had distinct and not yet described effects on the behaviour and endocrine system of the male offspring.

Adrenal Glands↗

Bulk and rhizosphere soil bacterial communities studied by denaturing gradient gel electrophoresis: plant-dependent enrichment and seasonal shifts revealed.

The bacterial rhizosphere communities of three host plants of the pathogenic fungus Verticillium dahliae, field-grown strawberry (Fragaria ananassa Duch.), oilseed rape (Brassica napus L.), and potato (Solanum tuberosum L.), were analyzed. We aimed to determine the degree to which the rhizosphere effect is plant dependent and whether this effect would be increased by growing the same crops in two consecutive years. Rhizosphere or soil samples were taken five times over the vegetation periods. To allow a cultivation-independent analysis, total community DNA was extracted from the microbial pellet recovered from root or soil samples. 16S rDNA fragments amplified by PCR from soil or rhizosphere bacterium DNA were analyzed by denaturing gradient gel electrophoresis (DGGE). The DGGE fingerprints showed plant-dependent shifts in the relative abundance of bacterial populations in the rhizosphere which became more pronounced in the second year. DGGE patterns of oilseed rape and potato rhizosphere communities were more similar to each other than to the strawberry patterns. In both years seasonal shifts in the abundance and composition of the bacterial rhizosphere populations were observed. Independent of the plant species, the patterns of the first sampling times for both years were characterized by the absence of some of the bands which became dominant at the following sampling times. Bacillus megaterium and Arthrobacter sp. were found as predominant populations in bulk soils. Sequencing of dominant bands excised from the rhizosphere patterns revealed that 6 out of 10 bands resembled gram-positive bacteria. Nocardia populations were identified as strawberry-specific bands.

Bacteria↗

Interleukin 4 induces transcription of the 15-lipoxygenase I gene in human endothelial cells.

The reticulocyte-type 15-lipoxygenase (15-LO-I) has been implicated in atherogenesis because of its capability of oxidizing low density lipoprotein. Therefore, we investigated the expression of the 15-LO-I gene in human umbilical vein endothelial cells (HUVEC). Nonactivated HUVEC did not exhibit detectable 15-LO-I mRNA. However, exposure of the cells to interleukin 4 (IL-4) induced the transcription of the 15-LO-I gene in a time- and concentration-dependent manner. Interestingly, this induction was not paralleled by a concomitant production of the functional 15-LO-I enzyme, as indicated by activity assays and immunoblotting. To gain more information about the mechanism of the induction process, we investigated IL-4-dependent activation of nuclear transcription factors for which binding sites were previously identified in the 5'-flanking region of the human 15-LO-I gene. Electrophoretic mobility shift assays revealed that IL-4 can activate signal transducer and activator of transcription 6, activator protein 2, GATA motif-binding transcription factor 1, nuclear factor 1, and SP-1 in HUVEC in a time- and concentration-dependent manner. Activation of these transcription factors was observed as early as 30 min after cytokine exposure. These data indicate that IL-4 upregulates the transcription of the 15-LO-I gene in human vascular endothelial cells, and this process may involve the activation of several nuclear transcription factors. The lack of active 15-LO-I protein in the presence of functional 15-LO-I mRNA suggests additional regulatory elements of 15-LO expression at posttranscriptional levels.

Arachidonate 15-Lipoxygenase↗

Specific or superfluous? Doubtful clinical value of granulocyte scintigraphy in osteomyelitis in children.

To study the clinical usefulness of granulocyte scintigraphy, eight children with clinical, laboratory and/or radiologic findings strongly suggestive of osteomyelitis were prospectively evaluated. Comparison was made with bone scintigraphy and magnetic resonance imaging. In adults, granulocyte scintigraphy is highly infection specific, although nonspecific findings (i.e. photopenic lesions) may also occur. Granulocyte scintigraphy was positive in one patient, false-negative in two and demonstrated nonspecific photopenic lesions in five children (62%). In conclusion, there appears to be little place for granulocyte scintigraphy in routine investigation of suspected ostoemyelitis in children.

Antibodies, Monoclonal↗