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S Krüger

Publications and source records attributed to S Krüger.

At least 73 records · Page 4Linked to original sources
PubMed2000

Over-expression of wild-type Rad51 correlates with histological grading of invasive ductal breast cancer.

Breast cancer is a major cause of cancer-related death in women. BRCA1 tumour-suppressor function is abolished in sporadic breast cancer by down-regulation of the protein level. This down-regulation inversely correlates with tumour grading. BRCA1 is part of a multiprotein complex, which also contains the recombination factor Rad51. Here we describe that in contrast to BRCA1, histological grading of sporadic invasive ductal breast cancer significantly correlates with over-expression of wild-type Rad51. These data suggest that in addition to the absence of the tumour-suppressor protein BRCA1, over-expression of wild-type Rad51 also contributes to the pathogenesis of a significant percentage of sporadic breast cancers and that other mechanisms than mutations must be responsible for this altered expression.

BRCA1 Protein↗
PubMed2000

Cathepsin K expression in human lung.

Tissue remodeling is crucial in different lung diseases, in the embryonal development as well as in bronchial carcinoma. Cathepsins were proposed to be involved in the degradation of matrix proteins. Cathepsin K is one of the most potent matrix-degrading cysteine proteinases known as yet. The elastinolytic and collagenolytic activity of this papain-like protease is comparable with that of neutrophil elastase. We have investigated the cathepsin K expression in normal adult lung tissues, in embryonal lung tissue and in bronchial carcinoma. With help of specific anti-cathepsin K antibodies it could be shown that cathepsin K was expressed in bronchial epithelial cells. These data could be confirmed at mRNA level using a quantitative RT-PCR as well as by visualisation of the specific enzymatic activity in epithelial cell lines. During the embryonal development cathepsin K was expressed in the epithelial cells of the developing bronchi. The expression seemed to be upregulated in parallel with the development of the bronchial and alveolar lumen. In the later phase of lung development the cathepsin K expression was restricted to bronchial epithelial cells. Furthermore, using quantitative RT-PCR it could be shown that cathepsin K-mRNA was upregulated in lung tumor tissues in comparison to normal tissues from the same patients. These data suggest that cathepsin K may play an important role in matrix remodeling of the lung under physiological and pathological conditions.

Bronchi↗
PubMed2000

The impaired immune response to diphtheria vaccination in elderly chronic hemodialysis patients is related to zinc deficiency.

Zinc deficiency causes abnormalities of the immune response. In chronic hemodialysis therapy abnormalities in zinc metabolism as well as an impaired immune response to vaccination have been reported. Therefore we performed a vaccination study against diphtheria and hypothesized that the response to diphtheria vaccination is related to serum zinc deficiency in hemodialysis patients. Serum zinc concentrations were assayed in 16 chronic hemodialysis patients (10 male, 6 female; mean age 65 years) without a documented vaccination history against diphtheria. Nine of these patients were triple immunized against diphtheria while seven received a single vaccination. The response to diphtheria vaccination was measured by ELISA detecting specific antibodies to diphtheria-toxoid. Seroconversion 6 and 12 months after vaccination was defined as the doubling of antibody titers in patients > or = 0.1 IU/ml prior to vaccination or as titers > 0.1 IU/ml in all other patients. Only 6/16 hemodialysis patients responded to immunization against diphtheria by specific antibody production (> 0.1 IU/ml). Twelve months after the single injection 3/7 patients seroconverted while six months after the triple vaccination 3/9 patients responded to immunization. This was not age-dependent, whereas in non-responders we detected significantly decreased serum zinc levels. In contrast, responders showed similar serum zinc levels as age-matched controls. Furthermore, we measured a decreased alpha 2-macroglobulin concentration only in the responders amongst the hemodialysis patients. Protection against diphtheria and the immune response to diphtheria vaccination in hemodialysis patients is poor. The failure to respond to active diphtheria vaccination is related to a significantly decreased serum zinc concentration in hemodialysis patients.

Aged↗
PubMed2000

Comorbidity of obsessive-compulsive disorder in recovered inpatients with bipolar disorder.

OBJECTIVE: To determine the frequency of obsessive-compulsive disorder (OCD) in inpatient subjects with bipolar disorder (BD) and to examine the clinical characteristics of BD subjects with OCD. METHOD: The sample consisted of 143 inpatient subjects with DSM-III-R BD-I and BD-NOS (BD-II), recovered from a current episode of either depression or mania. Demographic and clinical variables were obtained on the day of admission. Current comorbid conditions including OCD were determined by the Structured Clinical Interview for DSM-III-R Ifollowing recovery from the acute affective episode. RESULTS: The frequency of current OCD was 7% (N = 10). All BD subjects with OCD were BD-II, were male, and had a diagnosis of current dysthymia. They had fewer episodes and a higher incidence of prior suicide attempts than bipolar subjects without OCD. None of the bipolar subjects with OCD fulfilled criteria for cyclothymia. CONCLUSIONS: Our findings suggest that BD-II, OCD, dysthymia, and suicidality cluster together in some subjects with BD. We discuss the clinical implications of our findings.

Adult↗
PubMed2000

[Ulcerative colitis-associated colorectal carcinoma. DNA ploidy as indicator of impending malignant transformation?].

The onset of a malignant transformation in long-standing ulcerative colitis is difficult to predict. The value of the clinical and histomorphological parameters in current use is limited. It was thus aim of the present study to investigate the value of DNA-ploidy for the early detection of a malignant transformation in long-standing ulcerative colitis. This retrospective study comprised 20 patients with long-standing ulcerative colitis. The average observation time was 7.3 years (range: four to twelve years). All patients took part in a surveillance program and had between four and seven colonoscopies within a minimum period of time of five years. At these instances mucosal biopsies were taken in a standardized manner at eight different locations throughout the colon. These paraffin-embedded specimens (n = 542) were analyzed histomorphologically and DNA-cytometrically. During the observation time five patients developed an ulcerative colitis-associated colorectal carcinoma (UCA). In these patients epithelial dysplasias were not more common than in the remaining 15 cases. The vast majority of the specimen of the patients with UCA showed distinct DNA-cytometrical alterations, i.e. they were aneuploid. Such aneuploid mucosal cell populations were distributed over the whole colon, irrespectively of the later site of the carcinoma. These aneuploid lesions were found in one case eleven years, in an average seven years prior to the final diagnosis of a UCA. In contrast, the colon epithelium of the patients without UCA showed only proliferative-diploid DNA-distribution patterns during the observation time. In summary, affected patients had multiple highly aneuploid lesions of the colon mucosa at an average of seven years prior to the final diagnosis of UCA. These lesions came from macroscopically chronic inflamed tissue, and where histomorphologically without signs of dysplastic transformation. DNA-cytometrical investigations could thus be of additional predictive value for the individual risk assessment as regards an impending malignant transformation.

Adult↗
PubMed2000

[Radial k-scanning for real-time MR imaging of central and peripheral pulmonary vasculature].

PURPOSE: To depict the central and peripheral pulmonary vessel anatomy with real-time radial MR scanning without respiratory control. METHODS: Three healthy volunteers and one patient with pulmonary embolism proven by spiral CT angiography were studied with a 1.5 T MR imaging system. First, a breath-hold, contrast-enhanced MR angiography was performed for comparison of accuracy. Gradient echo images (TR 16 ms, TE 4 ms, flip angle 18 degrees) were obtained applying a combination of radial scanning and the sliding window reconstruction technique. A dedicated back-projector allowed data reconstruction in real-time with a frame rate of 20 images per second. Scanning was performed during free breathing. RESULTS: The described technique depicted the central and peripheral portions of the normal pulmonary anatomy with comparable image quality as the 3D contrast-enhanced angiography. Visualization of the pulmonary emboli as demonstrated by spiral CT was possible. CONCLUSION: Real-time radial scanning allows promising image acquisition of the pulmonary vasculature without respiratory control. Further technical improvements and clinical trials are required to evaluate its role in the diagnosis of vascular pathologies.

Adult↗
PubMed2000

[Hepatic Doppler perfusion index--a sensitive screening method for detecting liver metastases?].

UNLABELLED: The sonographic measurement of the Doppler perfusion index (DPI)--the ratio of blood flow in the hepatic artery to total liver blood flow--has been suggested to represent a method of detecting even small liver metastases. AIM: To evaluate the DPI measurement in our patients with liver metastases of colorectal cancer, gastric and bronchial carcinoma. METHOD: 36 patients with liver metastases were compared to 21 control subjects. The hepatic arterial and portal venous blood flows were calculated from the product of the average velocity of flow and the cross-sectional lumen of the vessel. Each measurement was performed three times by two independent examiners. RESULTS: Patients with metastases had a significantly higher hepatic blood flow and a significantly higher DPI (p = 0.0004; M +/- SD 0.23 +/- 0.11; r 0.06-0.52) compared with controls (M +/- SD 0.14 +/- 0.06, r. 0.05-0.26). No significant difference was seen in the portal vein blood flow. The DPI-values measured by the two examiners differed by 25.98% +/- 23.20. CONCLUSION: DPI values in patients with liver metastases differ from those in control subjects due to an increased hepatic arterial blood flow. No clear separation of the two groups was possible because DPI values overlapped. The inter observer agreement in DPI seems clinically acceptable.

Adult↗
PubMed2000

Interleukin-8 secretion of cortical tubular epithelial cells is directed to the basolateral environment and is not enhanced by apical exposure to Escherichia coli.

In upper urinary tract infections, tubular epithelial cells (TEC) may play a pivotal role in the initiation of the renal inflammatory response. They exert crucial immunological functions such as processing and presentation of foreign antigen, secretion of proinflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha) and chemokines (IL-8, MCP-1, ENA-78, and RANTES). Since monolayer cultures are a limited model for polarized tubular epithelial cells, we studied the side-dependent IL-8 secretion of TEC by using cell culture inserts as a basement membrane imitation. Primary cultures of proximal TEC were stimulated with differently fimbriated mutants of Escherichia coli, E. coli LPS, S-fimbria isolates, and IL-1alpha. IL-8 protein was measured by enzyme-linked immunosorbent assay, and IL-8-like biological activity was tested by measuring elastase release from polymorphonuclear cells in supernatants of the upper and lower compartments. IL-8 mRNA was compared by competitive PCR. IL-8 secretion by TEC into the basolateral environment was significantly higher than secretion into the apical compartment, representing the tubular lumen. However, stimulation of IL-8 secretion by TEC was restricted to IL-1alpha and was not inducible by E. coli mutants, S fimbriae, or lipopolysaccharide. With this in vitro model of polarized TEC, we show that luminal contact of TEC with uropathogenic E. coli does not result in enhanced IL-8 secretion. The basolaterally directed production of the neutrophil chemotactic factor IL-8 by TEC after stimulation with IL-1alpha might play an important role in the initiation of inflammatory cell influx into the renal parenchyma.

Base Sequence↗
PubMed2000

Prevalence of obsessive-compulsive disorder in schizophrenia and significance of motor symptoms.

To investigate the differences between schizophrenic subjects with and without obsessive-compulsive disorder (OCD), the authors systematically assessed 76 schizophrenic subjects for OCD. Subjects with and without OCD were then compared with regard to motor symptoms, including catatonia, and several measures of psychopathology. Treatment strategies were evaluated retrospectively. The 12 subjects with OCD (15.8%) had more motor symptoms, including catatonia, than non-OCD schizophrenic subjects. Some differences were found with regard to psychopathological symptoms. Treatment strategies also differed in the two groups. The high prevalence of motor symptoms in these subjects supports the hypothesis of a basal ganglia-frontal lobe connection linking OCD with schizophrenia.

Adult↗
PubMed2000

[Karl Ludwig Kahlbaum (1828-1899)--a protagonist in modern psychiatry].

Kahlbaum was one of the most influencial psychiatrists of the 19th century. He paved the way for Kraepelin and inspired the development of 20th century clinical psychiatry. With his work he contributed to new ideas in general psychopathology and in psychiatric nosology. He described "clinical state-course-entities" and developed the concept of "exogenous reaction types", which would later be known as the "Bonhoeffer-paradigm". Kahlbaum was also the first to differentiate between centripetal, intracentral and centrifugal psychic functions, which was later transformed into the "psychic reflex circuit" by Wernicke. The concept of organic versus non-organic psychoses proved to be a heuristically fruitful classification system even for modern psychiatry. Kahlbaum was the first German psychiatrist to describe several disorders and syndromes and to coin new psychiatric terminology for them, including paraphrenia, hebephrenia, catatonia and cyclothymia. These terms and their originally associated meaning are still in use today. Kahlbaum's ambitious scientific aim was to develop specific therapeutic strategies which were based on a methodologically and etiologically sound classification system.

Germany↗
PubMed2000

Cell cycle-dependent AgNOR analysis in invasive breast cancer.

OBJECTIVE: To investigate to what extent analysis of silver-stained nucleolar organizer regions (AgNORs) is cell cycle dependent in breast cancer and to assess the prognostic value of an AgNOR analysis that takes into consideration the cell cycle status of tumor cells. STUDY DESIGN: In 97 cases of invasive breast carcinoma, morphometric AgNOR analysis was performed in tumor cells with immunohistochemical MIB-1 reactivity (NORcyc analysis) and in MIB-1-negative tumor cells (NORnon analysis). Additionally, conventional (NORconv) analysis without preceding MIB-1 staining was done. Findings were compared with the Nottingham prognostic index (NPI). RESULTS: In comparison to noncycling tumor cells, cycling ones exhibited significantly higher AgNOR numbers (mean values, 3.84 +/- 1.09 vs. 2.40 +/- 0.78 per nucleus), higher total AgNOR areas (5.95 +/- 3.17 vs. 5.62 +/- 3.05 micron 2, NS) and significantly lower mean AgNOR areas (2.08 +/- 1.14 vs. 2.93 +/- 1.69 micron 2). When related to NPI, correlation coefficients of NORnon analysis were higher than those of NORcyc analysis but lower than those of NORconv analysis. Among the different AgNOR parameters, total AgNOR area correlated best with NPI. CONCLUSION: Cell cycle status has a high impact on AgNOR analysis. However, the best prognostic information in breast cancer is derived from an AgNOR analysis that considers both cycling and noncycling tumor cells.

Adult↗
PubMed2000

Psychopharmacotherapy of anorexia nervosa, bulimia nervosa and binge-eating disorder.

Pharmacotherapy for anorexia nervosa is considered to be of limited efficacy. However, many studies suffer methodological limitations, and the utility of newer drugs in the treatment of anorexia has not been examined yet. Although there have been more fruitful investigations on the efficacy of medication in the management of bulimia nervosa, there are still many unresolved issues regarding the optimal management of partial remission during the acute treatment phase and the intensity and duration of pharmacotherapy to achieve optimal prophylaxis. Selective serotonin reuptake inhibitors (SSRIs) control the binge urges in binge-eating disorder, but more trials are required to investigate the utility of SSRIs and other agents in maintenance treatment. We review the current status of psychopharmacotherapy for anorexia nervosa, bulimia nervosa and binge-eating disorder and evaluate the merits of newer agents in the treatment of these disorders.

Affect↗
PubMed2000

[Cellular proteases and invasion].

Cellular proteases are those proteases that are localized in the cytoplasm and on the cell surface, but not those secreted into the extracellular matrix. Proteases localized on the cell surface play a specific role in the invasion process of malignant tumor cells. These are activated by a relatively complicated cascade in which different cathepsins, the plasminogen activator system, plasmin, and the matrix metalloproteinases, including the membrane-type matrix metalloproteinases, play a major role. This article places emphasis on the biologic function and oncologic significance of cathepsins B and L, as well as on the urokinase plasminogen activator and the membrane-type matrix metalloproteinases localized on the cell surface. Recent investigations on these factors revealed that they are dependent on each other, such that the upregulation or downregulation also causes alterations in the regulation of the other factors. This fact alone elucidates the complexity of this system. Moreover, there is growing evidence that other proteases hitherto known to have other functions, e.g. as signal proteases in the immunologic system, may be important for invasion provesses. To provide an example of this, we describe the invasive potential of aminopeptidase N (APN/CD13). These recent results, which shed light on the role of further proteases in invasion processes, clearly show the complexity of this proteolytic system. Against this biologic background, it seems not to be promising to establish single proteases as distinct parameters for the prognosis of the metastatic potential of malignant tumors.

Endopeptidases↗
PubMed1999

Defective immune response to tetanus toxoid in hemodialysis patients and its association with diphtheria vaccination.

The incidence of infectious diseases is increased in patients with chronic renal failure. This is thought to be due to an impaired T cell stimulation by antigen presenting cells. Immunization programs are of great significance in the prevention of infections in immunocompromised individuals. However, the immune response to various vaccinations is impaired in patients with chronic renal failure. So far only few studies have focused on seroresponse to tetanus toxoid. Therefore we measured the levels of antitetanus toxoid antibodies in 71 hemodialysis patients with unknown vaccination history. The antibody levels were detected prior to and twelve months after a single "Td" or "Td-d-d" vaccination. Initially only 31 (44%) of the patients had a sufficient protection against tetanus. Of the unprotected patients 15 (38%) seroconverted after immunization, while 25 (63%) did not respond. We found a high association (p < 0.04, Fisher's exact test) between the efficacy of vaccination against diphtheria and tetanus. Out of 38 initially unprotected patients 27 (71%) showed a similar response to both vaccines: 9 (24%) individuals seroconverted, while 18 (47%) did not. Our data clearly demonstrate the need for frequent monitoring of antibody levels after immunization against tetanus and diphtheria in hemodialysis patients.

Antibodies, Bacterial↗
PubMed1999

[A long-term organic brain syndrome and brain stem symptoms in an undiagnosed dialysis-associated encephalopathy].

HISTORY AND CLINICAL FINDINGS: A 73-year-old woman in renal failure for the past 22 years had been on haemodialysis for 16 years. Because of hyperphosphataemia and peptic ulcers she had been on aluminium-containing antacids with a total intake over time of about 8 kg "pure" aluminium. Over the past 11 years she had biphasic symptoms of death anxieties and depression. She also had amnesic aphasia and some extrapyramidal symptoms as well as generalized convulsive seizures and recurrent falls. INVESTIGATIONS: Cranial computed tomography merely revealed signs of a microangiopathy and an age-related decrease in brain volume. The EEG showed intermittent changes while the CSF and ECG were unremarkable. There was no benzodiazepine or ethanol in the blood. TREATMENT AND COURSE: After excluding stroke with secondary epilepsy, uraemic encephalopathy was assumed to be the cause of the severe organic psychiatric syndrome. In the last few days before her death the patient had disturbance of consciousness and of breathing. She died during grotesque tossing movements, thought to be due to a brain stem stroke. Autopsy revealed high-grade myocardial hypertrophy caused by the hypertension, contracted kidney of vascular cause, hyperplasia of the parathyroid and calcification of the renal parenchyma as a sign of secondary parathyroidism. The CNS showed severe dialysis-associated encephalopathy with characteristic argyrophilic, aluminium-induced lysosomal intracytoplasmic inclusions in the choroid plexus epithelium, cortical glia and numerous neuron populations. Laser microprobe mass analysis (LAMMA) confirmed manifold increase in subcellular aluminium content, especially in the neuronal cytoplasm, also demonstrated by atom absorption spectrometry. Additional distinct deposition of beta A4-amyloid, typical of Alzheimer's disease, was probably age-related rather than associated with the dialysis and the aluminium uptake. CONCLUSION: Dialysis-associated encephalopathy must be taken into account as a possible cause of aetiologically uncertain neuropsychiatric symptoms in patients on chronic haemodialysis.

Aged↗
PubMed1999

[Malakoplakia of the colon].

We report on a 62-year-old female patient with melena in which polypoid lesions of the cecum were discovered endoscopically. Histological examination of mucosal biopsies revealed an inflammatory process with lots of histiocytes and so-called Michaelis-Gutmann bodies, leading to the diagnosis of a malakoplakia of the colon. No other organs were found affected. In the course of an antibiotic therapy, there was no melena detectable over a period of six months. Malakoplakia, an inflammation usually affecting the urogenital tract, is rarely found in the colon, with only 35 cases published until now. It is frequently associated with other diseases like neoplastic or inflammatory disorders, immune defect syndromes or heroin abuse. This spectrum is expanded by our report in which a long-standing alcohol abuse was found as an attendant disease.

Alcohol-Related Disorders↗
PubMed1999

[Prevalence and clinical significance of catatonic symptoms in mania].

OBJECTIVE: The study investigates the prevalence, clinical characteristics and implications of catatonic symptoms in mania. METHODS: Sixty-one in patients with DSM-III-R bipolar disorder, manic or mixed episode established by SCID were assessed for the presence of catatonia by a 21-item rating scale. Associated symptoms, comorbidity and severity of the manic episode were also systematically assessed. RESULTS: Nineteen patients fulfilled criteria for catatonic mania exhibiting between 5 and 16 catatonic symptoms. Catatonic manics had more mixed episodes, more severe manic symptoms, more general psychopathology, a higher prevalence of comorbidity, longer hospitalization and lower GAF-scores than the non-catatonics. CONCLUSIONS: The results indicate that catatonic symptoms are a marker of a more severe course and outcome in mania.

Adult↗