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Biomedical subjects

A Krüger

Publications and source records attributed to A Krüger.

At least 37 records · Page 2Linked to original sources
PubMed2001

Alagille syndrome associated with a paracentric inversion 20p12.2p13 disrupting the JAG1 gene.

Mutations in the human gene Jagged1 (JAG1) localized in 20p12 have been recently identified as causal for the anomalies found in patients with Alagille syndrome (AGS). This gene encodes a ligand for the Notch1 transmembrane receptor, which plays a key role in cell-to-cell signaling during differentiation and is conserved from C. elegans to human. We report a paracentric inversion (PAI) of chromosome 20p12.2p13 in an individual with AGS who also had alpha-1-antitrypsin deficiency. To our knowledge, this is the first published case of PAI involving the short arm of chromosome 20. Using FISH, fiberFISH, and molecular studies with a approximately 40 kb cosmid clone encompassing the entire 36 kb JAG1 gene, we demonstrate that the gene was disrupted by the inversion breakpoint between exons 5 and 6. An unusual association between two most common causes of chronic liver disease in childhood, AGS and alpha-1-antitrypsin deficiency, as well as their influence on the proband's abnormal phenotype are discussed.

Alagille Syndrome↗
PubMed2001

Phenotypic findings due to trisomy 7p15.3-pter including the TWIST locus.

We report on a three-month-old boy with a 46,XY,der(Y)t(Y;7)(p11.32;p15.3) karyotype and growth deficiency, postnatal microcephaly with large fontanels, wide sagittal and metopic sutures, hypertelorism, choanal stenosis, micrognathia, bilateral cryptorchidism, hypospadias, abnormal fingers and toes, and severe developmental delay. FISH studies showed partial trisomy 7p resulting from a de novo unbalanced translocation. The application of molecular probes from the TWIST gene region (7p15.3-p21.1) and probes from the pseudoautosomal region (PAR) demonstrated that the 7p15.3-pter fragment was translocated onto Yp with the breakpoint within approximately 20 kb from the Yp telomere. We discuss the possible role of the TWIST gene in abnormal skull development and suggest that trisomy 7p cases with delayed closure of fontanels can be a result of TWIST gene dosage effect.

Abnormalities, Multiple↗
PubMed2001

Kabuki syndrome-like features associated with a small ring chromosome X and XIST gene expression.

Although clinical features in Kabuki syndrome (KS; Niikawa-Kuroki syndrome) have been well defined, the underlying genetic mechanism still remains unclear. We report a 9-year-old girl with typical KS-like facial appearance, skeletal and dermatoglyphic abnormalities, severe mental retardation, and growth deficiency. In 60 of 100 GTG-banded metaphases from peripheral blood lymphocytes, a ring chromosome smaller than a G group chromosome was found, which, according to reverse painting, consisted of Xq11.1q13. The proband's karyotype was described as mos45,X/46,X,+r(X). Several loci were analyzed with fluorescence in situ hybridization (FISH) and microsatellite markers revealing that one r(X) breakpoint mapped proximal to DXS422 (Xp11.21) and the second mapped distal to XIST gene, between loci DXS128E and DXS441 (Xq13.2). Uniparental disomy for X and r(X) was excluded and the paternal origin of r(X) was identified. XIST expression was demonstrated by nested reverse transcription polymerase chain reaction (RT-PCR) using primers spanning exons 5, 6i, and 6 in RNA prepared from lymphocytes. The observation of XIST expression is in contrast to two other cases in which the XIST gene was either not present on r(X) or not expressed. To our knowledge, this is the first case of Kabuki-like syndrome manifestations with r(X) and XIST expression.

Abnormalities, Multiple↗
PubMed2001

A new protein expressed in bone marrow cells and osteoblasts with implication in osteoblast recruitment.

To study osteoblast recruitment from bone marrow cells, a rat femur cDNA library was screened by in situ hybridization for novel mRNA sequences that are frequently expressed in both marrow cells and osteoblasts. One isolated clone, called RP59, is described here. Northern blots indicated two bands of 2.6 and 2.8 kb in femur and spleen, tissues containing high amounts of immature mesenchymal cells, and no or little expression in other tissues. The cDNA sequence revealed a reading frame for a repetitive protein composed of arrays of 14-mers and phased phosphorylation sites. Antisera versus RP59 detected a single band of 90 kDa by Western blotting of femur extract. Immunohistochemistry indicated strong RP59 presence in the cytoplasm of bone marrow cells and weaker presence in nuclei of osteoblasts. Intermediate stages were found between strongly labeled, round, free bone marrow cells and weaker labeled, fibroblast-like young osteoblasts associated with bone matrix. These data indicated that marrow cells with high RP59 content were recruited into growing bone tissue. RP59 may help to study the transition of bone marrow cell to osteoblast in more detail.

Amino Acid Sequence↗
PubMed2001

Hydroxamate-type matrix metalloproteinase inhibitor batimastat promotes liver metastasis.

Overexpression of matrix metalloproteinases (MMPs) facilitates tumor cell invasion. Synthetic MMP inhibitors such as batimastat have been designed to treat cancer. We report that because of batimastat treatment, human breast carcinoma cells metastasized to the liver in nude mice and that an increase of liver metastases of murine T-cell lymphoma cells was observed in syngeneic mice. Batimastat treatment also caused liver-specific overexpression of MMPs-2, -9, and mRNA up-regulation of angiogenesis factors and caspase-1, even in tumor-free animals. Induction of organ-specific side effects need to be taken into account regarding further development and clinical use of synthetic MMP inhibitors.

Angiogenesis Inducing Agents↗
PubMed2001

[Pressure distribution measurements during use of wheelchairs].

There is a growing number of mobility-impaired and wheelchair-dependent patients caused by diseases and injuries of the central nervous system. The risk is high for pressure sores to develop due to disturbances of the motor, sensory, and autonomic nervous system. Numerous seating systems for prophylaxis and treatment of decubitus ulcer are available. To identify risk parameters, the literature on animal experiments regarding pressure ulcers was reviewed. A study on the reproducibility of the analysis method with capacitive sensors tested in ten paraplegics with 470 measurements is presented. It shows the reliability of the procedure.

Biomechanical Phenomena↗
PubMed2001

Procalcitonin following elective partial liver resection--origin from the liver?

BACKGROUND: The origin of the inflammatory peptide procalcitonin (PCT) is still unknown. In the present study PCT concentrations in arterial and hepatic-venous blood were examined in patients undergoing elective partial liver resection (LR) using a fiberoptic pulmonary arterial catheter placed in a liver vein to obtain further information on the origin of PCT. METHODS: In 28 patients (21 male/7 female; average age of 58.8+/-8.8 years) undergoing LR, arterial and hepatic venous PCT concentrations were measured during 24 h perioperatively. The parallel blood withdrawals occurred immediately before the Pringle maneuver (Hx), 2 min, 1, 2, 6, 12, and 24 h after Hx. Over the whole period, the oxygen saturation in hepatic venous blood (ShvO2) was monitored. PCT concentrations were assayed by immunoluminometry. RESULTS: We observed a significant increase in PCT concentration already 6 h after Hx compared to the values before Hx. Twenty-four hours after Hx we found the highest plasma concentrations. It was conspicuous that hepatic venous PCT concentrations were always higher than the arterial ones (significantly from the 6th hour after Hx). There was no correlation between the courses of ShvO2 and PCT rise. A significant correlation was verified between Hx duration and PCT concentration measured 24 h after Hx both in the hepatic venous and arterial blood. CONCLUSIONS: The results of our investigation can be interpreted as evidence that liver (or the hepatosplanchnicus?) is a source of PCT. The mechanism of PCT induction cannot be clarified by our study: whether the induction of PCT was caused by an endotoxin translocation during the impeded splanchnic outflow or by the direct surgery-induced lesion (hypoxia) of the liver remains unclear. However, the latter appears more probable because of the observed correlation between Hx duration and PCT concentration rise.

Calcitonin↗
PubMed2001

Two cases of autochthonous Plasmodium falciparum malaria in Germany with evidence for local transmission by indigenous Anopheles plumbeus.

Autochthonous Plasmodium falciparum malaria (PFM) in Central Europe has been reported repeatedly, transmission of the parasite being attributed to blood transfusion or imported P. falciparum-infected vectors. We report two cases of PFM in German children without travel history to malaria-endemic areas. Both infections occurred during a stay in a hospital where a child from Angola with chronic P. falciparum infection was hospitalized at the time. Known routes of transmission, such as imported mosquitoes or blood transfusion, were very unlikely or could be excluded, whereas evidence was obtained for transmission by the indigenous mosquito species Anopheles plumbeus.

Adult↗
PubMed2001

Clinical relevance of the plasminogen activator inhibitor type 1--a multifaceted proteolytic factor.

The plasminogen activator inhibitor type-1 (PAI-1) is a multifaceted proteolytic factor. It not only functions as an inhibitor of the protease uPA (urokinase-type plasminogen activator), but also plays an important role in signal transduction, cell adherence, and cell migration. Thus--an apparent paradox considering its name--although it inhibits uPA during blood coagulation, it actually promotes invasion and metastasis. In the early 1990s, clinical evidence associated elevated PAI-1 levels in tumor tissue with poor clinical outcome in primary breast cancer. These clinical data have since been supported by experimental evidence that the concerted action of uPA, its cell surface receptor uPA-R, and PAI-1 facilitates invasion and metastasis. The strong prognostic impact of PAI-1 in primary breast cancer has been validated by international research groups assessing fresh tumor tissue extracts by ELISA. There is clinical evidence that high-risk patients with elevated PAI-1 in their tumor benefit from adjuvant systemic therapy. uPA also has a strong prognostic impact in primary breast cancer. In node-negative breast cancer, risk-group selection for adjuvant systemic therapy based on tumor levels of both PAI-1 and uPA is close to routine clinical use. Also in other malignancies such as ovarian, esophageal, gastric, colorectal or hepatocellular cancer, elevated PAI-1 is associated with tumor aggressiveness and poor patient outcome. This abundant clinical evidence implicating PAI-1 as a key factor for tumor invasion and metastasis renders it a promising target for tumor therapy. Novel therapeutic approaches targeting the PAI-1/uPA interaction are already in pre-clinical testing.

Biomarkers, Tumor↗
PubMed2001

High level synthesis of recombinant soluble urokinase receptor (CD87) by ovarian cancer cells reduces intraperitoneal tumor growth and spread in nude mice.

Focussing of the serine protease urokinase (uPA) to the tumor cell surface via interaction with its receptor (uPAR) is an important step in tumor invasion and metastasis. The human ovarian cancer cell line OV-MZ-6#8 was stably transfected with expression plasmids either encoding cell-associated uPAR (GPI-uPAR) or a soluble form of uPAR (suPAR) lacking its glycan lipid anchor. In vitro, high level synthesis of functionally active recombinant suPAR inhibited cell proliferation and led to reduced cell-associated fibrin matrix degradation, whereas fibrinolytic activity was increased in OV-MZ-6#8 cells overexpressing GPI-uPAR. Both OV-MZ-6#8-derived clones were inoculated into the peritoneum of nude mice and tested for tumor growth and spread. High level synthesis of recombinant suPAR (without altering the physiological expression levels of GPI-uPAR and uPA in these cells) resulted in a significant reduction of tumor burden (up to 86%) in the xenogeneic mouse model. In contrast, overexpression of GPI-uPAR in tumor cells did not affect tumor growth. Our results demonstrate that high levels of suPAR in the ovarian cancer cell vicinity can act as a potent scavenger for uPA, thereby significantly reducing tumor cell growth and cancer progression in vivo.

Animals↗
PubMed2001

Prognostic impact of proteolytic factors (urokinase-type plasminogen activator, plasminogen activator inhibitor 1, and cathepsins B, D, and L) in primary breast cancer reflects effects of adjuvant systemic therapy.

PURPOSE: Prognostic and predictive impact of five proteolytic factors associated with tumor invasion and metastasis in primary breast cancer were evaluated after long-term follow-up. EXPERIMENTAL DESIGN: Antigen levels of urokinase-type plasminogen activator, plasminogen activator inhibitor-1 (PAI-1), Cathepsins B, D, and L were determined using immunochemical assays in primary tumor tissue of 276 patients. RESULTS: During follow-up (median 109 months), 119 (43%) patients relapsed, and 117 (42%) died. In the whole collective, lymph node status (P < 0.001; RR 3.8), Cathepsin L (P < 0.001; RR 2.6), and PAI-1 (P = 0.027; RR 1.7) were the only independent significant factors in multivariate analysis for disease-free survival (DFS). For overall survival (OS), lymph node status (P < 0.001; RR 2.9), Cathepsin L (P = 0.017; RR 1.9), PAI-1 (P = 0.01; RR 1.9), and grading (P = 0.026; RR 1.7) were significant. In the node-negative subgroup, PAI-1 was the only significant factor for DFS (P = 0.004; RR 3.7) and the strongest factor (P = 0.004; RR 3.7) for OS next to grading (P = 0.017; RR 3.1). In node-positive patients, Cathepsin L was the only significant factor for both DFS (P < 0.001; RR 3.2) and OS (P = 0.003; RR 2.5). For all proteolytic factors but Cathepsin L, the univariate prognostic impact on DFS was substantial in patients without adjuvant systemic therapy but was diminished if adjuvant therapy had been administered. Cathepsin L maintained its strong prognostic impact on DFS even in patients with adjuvant endocrine therapy (P = 0.01; RR 2.8). CONCLUSIONS: The observed effect of adjuvant systemic therapy on their prognostic strength suggests that the assessed proteolytic factors supply predictive information on therapy response.

Adult↗
PubMed2000

Chemical and biochemical composition of caviar from different sturgeon species and origins.

The chemical and biochemical composition of caviar in 22 specimens of wild caught and of 2 farmed animals were measured. The results include grain size, protein and fat content, fatty acid composition of triglycerides and phospholipids, as well as the concentrations of relevant heavy metals and chlorinated hydrocarbons. The average protein content varied between 26.2 and 31.1% (wet weight) and fat from 10.9 to 19.4% (wet weight) with lowest values for caviar from farmed sturgeon. The triglycerides and phospholipids contained more n-3 fatty acids, especially eicosapentaenoic and docosahexaenoic acid than n-6 fatty acids. The copper and zinc concentrations varied between 1.20 and 1.69 and 10.3 and 12.4 mg/kg (wet weight), respectively. These values reflect the elevated requirement of sturgeons for these components. Lead content varied between 0.06 and 0.15 mg/kg (wet weight). The cadmium concentrations were less than 5 micrograms/kg (wet weight) leading to the conclusion that no accumulation took place in the eggs. The concentrations of sigma DDT and sigma PCB were extremely high in caviar from Huso huso compared to the samples of the other species thus reflecting the different food habits leading to increased bio-accumulation.

Animals↗
PubMed2000

Reduction of breast carcinoma tumor growth and lung colonization by overexpression of the soluble urokinase-type plasminogen activator receptor (CD87).

The serine protease urokinase-type plasminogen activator, uPA, when bound to its specific receptor, uPAR (CD87), plays a significant role in tumor cell invasion and metastasis. In breast cancer, enhanced uPA antigen in the primary tumor is correlated with poor prognosis of the patient. In an in vivo nude mouse model, we tested tumor growth and metastasis of human breast carcinoma cells that had been transfected with an expression plasmid encoding a soluble form of uPAR (suPAR). We explored, whether suPAR/uPA interaction reduces the binding of uPA to cell surface-associated uPAR, and, as a consequence, could suppress tumor growth and metastasis of the human breast cancer cell line MDA-MB-231 BAG. Overexpressed, secreted suPAR was shown to bind and thus scavenge the uPA secreted by the transfected lines suPAR3 and suPAR10. In vitro, an overexpression of suPAR did not alter the proliferation rate of the transfected tumor cells, nor did it affect the expression of uPA. Overexpression of suPAR led to a reduction in the plasminogen activation-related proteolytic activity of breast carcinoma cells. Primary tumor growth in the mammary fat pad of nude mice was followed up for 52 days. Overexpression of suPAR correlated with a reduction in tumor growth (from day 21, reaching 30% by day 34) as well as lung colonization (lung metastasis-positive mice in suPAR3: 4 of 17; suPAR10: 3 of 10; parental MDA-MB-231 BAG: 13 of 18). We conclude that suPAR overexpression leading to effective scavenge of uPA impairs proteolysis as well as the tumor growth and metastatic potential of breast carcinoma cells in vivo.

Animals↗
PubMed2000

Molecular identification and phylogeny of East African Simulium damnosum s.l. and their relationship with west african species of the complex (Diptera: Simuliidae).

The phylogenetic relationships of East and West African members of the Simulium damnosum complex were studied by sequence analyses of the mitochondrial 16s ribosomal RNA (rRNA) gene. Results suggest that: (i) the S. damnosum complex is divided into an East and a West African clade, and (ii) S. pandanophilum and the cytoform 'Kiwira' form an East African subbranch distinct from the 'Sanje' group. In contrast to former assumptions from cytogenetic analyses, our molecular data do not support a direct relationship between the East African S. kilibanum and the West African S. squamosum. Length differences of the rDNA internal transcribed spacer 1 (ITS-1) turned out to be useful to distinguish between cytoforms.

Africa↗
PubMed2000

Tripled semitendinosus anterior cruciate ligament reconstruction with Endobutton fixation: a 2-3-year follow-up study of 35 patients.

We evaluated the clinical outcome of tripled semitendinosus tendon ACL reconstruction with femoral Endobutton (Acufex, Smith&Nephew, Andover, MA) and tibial Suture Washer (Acufex, Smith&Nephew, Andover, MA) (n 29) or post screw fixation (n 6) in 35 patients on an average of 28 (20-37) months after surgery. On the basis of IKDC criteria, 22 patients showed a normal or nearly normal knee function and 25 patients had a KT 1000 maximal manual side-to-side difference of < or =5 mm at follow-up. Subjectively, 28 patients graded their knee function as normal or nearly normal. The average Lysholm score was 88 points, average OAK score 90 points and average modified HSS score 93 points. 19 patients reached their preinjury level of activity at follow-up. The postoperative Lachman test was < or =1+ in 24 patients and 24 patients also showed an absent pivot shift. Significant bone tunnel enlargement occurred in 26 patients on the femoral side and in 23 patients on the tibial side. We found no correlation between bone tunnel enlargement and clinical outcome. The clinical outcome of tripled semitendinosus tendon ACL reconstruction with Endobutton fixation on the femoral side was not entirely satisfactory. The procedure was associated with a high incidence of bone tunnel enlargement in this series.

Activities of Daily Living↗
PubMed2000

The cytotaxonomy of Simulium damnosum s.l. (Diptera: Simuliidae) from the Thyolo onchocerciasis focus in Malawi and description of a new member of the complex.

Larvae of the Simulium damnosum complex were collected in southern Malawi, in particular from the Thyolo onchocerciasis focus. Cytological identifications revealed the occurrence of S. (Edwardsellum) thyolense sp.nov., S. kilibanum Gouteux, 'Ketaketa', a new cytoform tentatively designated 'Mwamphanzi', and two unassigned specimens. Simulium thyolense sp.nov. is presumably the major vector of Onchocerca volvulus in the area, but it remains possible that the other cytospecies are secondary vectors. Simulium thyolense sp.nov. is most appropriately classified near the 'Sanje' subcomplex, whereas 'Mwamphanzi' and the unassigned specimens are members of the 'Ketaketa' subcomplex.

Animals↗
PubMed2000

Reactive bone marrow changes in infectious spondylitis: quantitative assessment with MR imaging.

PURPOSE: To evaluate diffuse, reactive bone marrow changes in unaffected vertebrae on magnetic resonance (MR) images in patients with proved infectious spondylitis. MATERIALS AND METHODS: Percentage signal intensity increase of the unaffected bone marrow on contrast material-enhanced MR images (percentage enhancement) was calculated retrospectively in 22 cases of infectious spondylitis and 86 cases without bone marrow disease. Multiple regression analysis and Student t test statistics were performed. RESULTS: Multiple regression analysis showed a significant influence of age and the presence of spondylitis on the values of percentage enhancement (P: <.001). For those aged 35 years or younger, the mean percentage enhancement was 43.2% +/- 4.0 for patients with infectious spondylitis (n = 3) and was 26.4% +/- 8.6 for the control group (n = 23). For those older than 35 years, the mean percentage enhancement was 28.2% +/- 12.2 for patients with infectious spondylitis (n = 19) and 17.5% +/- 7.9 (P: <.001) for the control group (n = 63). Six (27%) of 22 patients with infectious spondylitis showed abnormal percentage enhancement values in unaffected bone marrow when the upper limit of the normal value was 2 SDs above the mean of the control group. CONCLUSION: On MR images, reactive bone marrow changes can be found in unaffected vertebrae in patients with infectious spondylitis. The signal intensity changes and increased percentage enhancement associated with this disease are similar to those of myeloproliferative and diffuse neoplastic disorders and bone marrow stimulation in hemolytic anemia.

Adult↗