PubMed Health⌕ Search

Biomedical subjects

M Haase

Publications and source records attributed to M Haase.

At least 19 recordsLinked to original sources
PubMed2006

IGF-II serum levels are normal in children with Silver-Russell syndrome who frequently carry epimutations at the IGF2 locus.

CONTEXT: Epigenetic mutations of 11p15 encompassing IGF2 are present in short children with Silver-Russell syndrome (SRS) with high frequency (31-50%). It has been speculated that these mutations characterized by demethylation of ICR1 cause diminished IGF2 expression. OBJECTIVE: We aimed to determine the prevalence of pathologically low IGF-II serum levels in children with SRS. SUBJECTS: SRS was defined by birth weight or length below the 3rd percentile, lack of postnatal catch-up growth, and the presence of two of the following characteristics: typical face, relative macrocephaly, and skeletal asymmetry. Serum samples of 30 patients were available. Mean age was 5.4 +/- 2.1 yr. METHODS: The serum levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-2, and IGFBP-3 were measured by RIA and compared with age-related reference values and with serum concentrations measured in age- and gender-matched controls born small for gestational age (SGA), but lacking major dysmorphic features. Analysis of genomic DNA was possible in a subgroup of children with SRS: the methylation status of the ICR1 locus on 11p15 and the parental origin of chromosome 7 were analyzed in 9 and 23 children, respectively. RESULTS: Demethylation of ICR1 was found in 44% and uniparental disomy in 17% of the tested children with SRS. The median IGF-II serum level in SRS was 441 microg/liter (range, 238-875). This was significantly higher than in the SGA controls: 387 microg/liter (range, 265-596) (P < 0.03), but below the median value of the age-related reference, which was 532 microg/liter. The four children with SRS and ICR1 demethylation had high-normal and normal IGF-II serum levels that were higher than the levels of their SGA controls. IGF-I, IGFBP-2, and IGFBP-3 serum levels were not different between the SRS children and their SGA controls. CONCLUSIONS: Our data render it unlikely that demethylation of ICR1 on 11p15 does cause diminished IGF-II serum levels in children with SRS. This observation does not exclude deficient IGF-II action before birth.

Case-Control Studies↗
PubMed2006

Development and characterization of monoclonal antibodies for the immunohistochemical detection of glycodelin A in decidual, endometrial and gynaecological tumour tissues.

AIMS: Glycodelin is a glycoprotein with a molecular weight of 28 kDa. Unusual LacdiNAc structures have been identified on glycodelin A, isolated from amniotic fluid. Three major functions of this glycoprotein have been identified. Glycodelin is an immunosuppressive molecule, a marker of morphological differentiation, and a contraceptive. Because no monoclonal antibodies for glycodelin A are commercially available, our aim was to develop and characterize three monoclonal antibodies against this glycoprotein. METHODS AND RESULTS: Glycodelin A was purified from amniotic fluid by three chromatographic steps and its purity was checked by SDS-PAGE. Antibodies were generated from immunized BALB/c mice. Three IgG1 monoclonal antibodies detecting glycodelin A were cloned. All three antibodies recognized carbohydrate structures of glycodelin A and did not cross-react with glycodelin S. They are applicable to immunohistochemistry (frozen and paraffin sections), ELISA and Western blots. CONCLUSION: The new antibodies can be used for the detection of glycodelin A in frozen and paraffin-embedded decidual and endometrial tissue. One antibody (A87-B/D2) can be used for the detection of glycodelin in endometrial and ovarian tumour tissues. Because glycodelin A is a major secretory endometrial product during the luteal phase, in early pregnancy and in gynaecological tumours, the new antibodies are, potentially, valuable tools for the study of endometrial development and tumour progression.

Amniotic Fluid↗
PubMed2005

The effect of nanocrystal surface structure on the luminescence properties: photoemission study of HF-etched InP nanocrystals.

InP nanocrystals with narrow size distribution and mean particle diameter tunable from approximately 2 up to approximately 7 nm were synthesized via the dehalosilylation reaction between InCl3 and tris(trimethylsilyl)phosphine. Specific capping of the nanocrystal surface with a shell of organic ligands protects the nanocrystals from oxidation and provides solubility of the particles in various organic solvents. InP nanocrystals with enhanced photoluminescence (PL) efficiency were obtained from the initial nanocrystals by photoassisted etching of the nanocrystal surface with HF. The resulting PL quantum efficiency of InP nanocrystals dispersed in n-butanol is about three orders of magnitude higher when compared to the nonetched InP samples and approaches approximately 40% at room temperature. High-resolution photoelectron spectroscopy with the use of synchrotron radiation was applied to reveal the changes of the nanocrystal surface responsible for the dramatic improvement of the PL efficiency. The analysis of high-resolution P 2p core-level spectra confirmed significant changes of the nanocrystal surface structure induced by the postpreparative treatments and allowed us to propose the description of the etching mechanism. In the nonetched InP nanocrystals, some surface P atoms generate energy states located inside the band gap which provide nonradiative recombination pathways. Photoassisted treatment of InP nanocrystals with HF results in selective removal of these phosphorous atoms from the nanocrystal surface. The reconstructed surface of the etched InP nanocrystals is terminated mainly with In atoms and is efficiently passivated with tri-n-octylphosphine oxide ligands.

Journal Article↗
PubMed2005

Time-resolved measurements of intramolecular energy transfer in single donor/acceptor dyads.

We have investigated electronic excitation energy transfer in a specifically designed bichromophoric donor/acceptor dyad in which the donor (perylenediimide) and acceptor (terrylenediimide) are linked by a rigid heptaphenyl-spacer. Because of the choice of the bridge, which defines the distance and orientation of the two chromophores, donor as well as acceptor emission is observed. The significantly smaller photostability of the donor allows for time-resolved measurements of the acceptor emission at the single-molecule level with and without energy transfer from the donor. By analyzing the differences of the rise/decay profiles for both pathways, we could determine time constants of energy transfer with high accuracy for single dyads. The results show that the experimental approach presented here works even for situations in which the energy transfer times are smaller than the temporal resolution of the detection system.

Journal Article↗
PubMed2005

Activity of sirolimus in patients with myelodysplastic syndrome--results of a pilot study.

The pathophysiology of the myelodysplastic syndromes (MDS) involves disturbed regulation of angiogenesis, apoptosis, proliferation and differentiation as well as immune surveillance. Increasing data suggest that sirolimus might affect these pathways positively, thus being of possible therapeutic benefit in patients with this disease. Nineteen patients (n = 19) with a median age of 72 years (range 54-80 years) diagnosed with MDS received sirolimus orally with a target blood concentration of 3-12 ng/ml. Sirolimus was administered for a median of 3.7 months (range 0.3-11 months). Three patients [1 x refractory anaemia with excess blasts (RAEB)-2, 1 x RAEB-1, 1 x refractory cytopenia with multilineage dysplasia] showed either a major (1 x platelet, 1 x neutrophil) or a minor (1 x erythroid, 2 x platelet) haematological response according to International Working Group criteria. Major side-effects were hyperlipidaemia (n = 4), stomatitis (n = 3), thrombocytopenia (n = 2) and urinary tract infection (n = 1). These data suggest that sirolimus has activity in a subset of patients with more advanced MDS.

Administration, Oral↗
PubMed2005

Rapid and convergent evolution of parental care in hydrobiid gastropods from New Zealand.

Although parental care occurs in most phyla encompassing a wide array of forms, little is known about its evolution in invertebrates. Two types of egg capsules have been known among ovoviviparous New Zealand hydrobiid gastropods, elastic capsules and simple membranes. Based on a phylogenetic analysis using two mtDNA sequence fragments, I asked whether the second state was derived from the first or whether brooding had multiple origins. The evolution of ovoviviparity was also investigated in the context of habitat transition between brackish and freshwater. Maximum parsimony and Markov chain models of character state transformations in a maximum likelihood framework suggested that hydrobiids have invaded freshwater three times independently. Two of these invasions were followed by the evolution of ovoviviparity, probably in adaptation to changing water levels during periods of irregular precipitation. The syntopy of two congeneric species, one oviparous and the other one brooding, indicated that the transition between reproductive modes must have occurred rapidly.

Animals↗
PubMed2003

Mitochondrial differentiation in a polymorphic land snail: evidence for Pleistocene survival within the boundaries of permafrost.

The genetic differentiation of populations having colonized formerly unsuitable habitats after the Pleistocene glaciations depends to a great extent on the speed of expansion. Slow dispersers maintain their refugial diversity whereas fast dispersal leads to a reduction of diversity in the newly colonized areas. During the Pleistocene, almost the entire current range of the land snail Arianta arbustorum has repeatedly been covered with ice or been subjected to permafrost. Owing to the low potential for dispersal of land snails, slow (re)colonization of the wide range from southern refugia can be excluded. Alternatively, fast, passive dispersal from southern refugia or survival in and expansion from multiple refugia within the area subjected to permafrost may account for the current distribution. To distinguish between these scenarios we reconstructed a phylogeography based on the sequences of a fragment of the cytochrome oxidase I from 133 individuals collected at 45 localities and analysed the molecular variance. Seventy-five haplotypes were found that diverged on average at 7.52% of positions. This high degree of diversity suggests that A. arbustorum is an old species in which the population structure, isolation and the hermaphroditic nature have reduced the probability of lineage extinction. The genetic structure was highly significant with the highest variance partition found among regions. Geographic distance and mitochondrial differentiation were not congruent. Lineages had overlapping ranges. The clear genetic differentiation and the patchy pattern of haplotype distribution suggest that colonization of formerly unsuitable habitats was mainly achieved from multiple populations from within the permafrost area.

Animals↗
PubMed2001

Identification of a novel gene on chromosome 13 between BRCA-2 and RB-1.

METHODS AND RESULTS: By differential display we isolated a new cDNA-fragment, named C13, that is downregulated in malignant prostate tissues. Northern hybridization revealed the fragment to be part of 3.0 and 4.4 kb mRNAs. Fluorescence in situ hybridization, Southern blotting and radiation hybrid mapping demonstrated a chromosomal localization of C13 on 13q12-14 closest to the SHGC-34125 marker. In the 5% chromosomal environment of C13 we detected changes of the allelic status in 13 of 21 prostate cancers. A downregulation was detected at the mRNA level in patients with advanced carcinoma. The 3.0 kb full length cDNA clone encodes a protein with an open reading frame of 2,202 bp or 733 amino acids. The corresponding protein contains a putative nuclear localization signal, several glutamine clusters and an alpha-helix-rich domain. By in situ RNA hybridization we could demonstrate the mainly epithelial expression of the C13 mRNA in prostatic tissue. CONCLUSIONS: The localization of C13 between the tumor suppressor genes BRCA-2 and RB-1, the detected allelic imbalances, the downregulation of its mRNA in some prostatic cancer tissues, the epithelial expression and the described protein structure suggest that this gene encodes a protein that may have tumor or metastasis suppressing function in prostate tissue.

BRCA2 Protein↗
PubMed2001

Albright's hereditary osteodystrophy associated with cerebellar pilocytic astrocytoma: coincidence or genetic relationship?

Albright's hereditary osteodystrophy (AHO) is a rare inherited disease characterized by skeletal abnormalities, short stature, and, in some cases, resistance to parathyroid hormone, resulting in pseudohypoparathyroidism (PHP). Heterozygous inactivating mutations of the GNAS1 gene are responsible for reduced activity of the alpha subunit of the Gs protein (G(Salpha)), a protein that mediates hormone signal transduction across cell membranes. G(salpha) is also known to have oncogenic potentials, leading to the development of human pituitary tumors and Leydig cell tumors. Here, we report the 1st case, a 3.5-year-old girl, with classic AHO phenotype and PHP type 1A associated with a cerebellar pilocytic astrocytoma. Coincidence or genetic relationships of both diseases are discussed according to molecular findings and current literature.

Adult↗
PubMed2000

Frequent loss of heterozygosity at the 19p13.3 locus without LKB1/STK11 mutations in human carcinoma metastases to the brain.

Inactivating germline mutations of the novel putative tumor-suppressor gene LKB1/STK11 at 19p13.3 have been shown to cause Peutz-Jeghers syndrome (PJS), an autosomal dominantly inherited disease characterized by a predisposition to mucocutaneous pigmentations, as well as various benign and malignant neoplasms. To elucidate the role of LKB1/STK11 in the carcinogenesis of primary and secondary human brain tumors, a total of 309 tumors were analyzed for loss of heterozygosity (LOH) at microsatellite loci D19S886, DI9S878, and D19S565. Low LOH rates were observed for glioma (17.3%, n = 139), meningioma (5.3%, n = 57), schwannoma (0%, n = 21), pituitary adenoma (18.8%, n = 16), primary CNS lymphoma, neuroblastoma, plasmocytoma, medulloblastoma, germinoma, and papilloma of the choroid plexus (6.6%, n = 15). In contrast, brain metastases exhibited a mean LOH frequency of 42.6% (n = 61), with breast (56.3%) and lung cancer metastases (58.3%) being most frequently affected. Genomic DNA sequencing of the complete coding region of LKB1/STK11 was performed in all brain metastases exhibiting LOH (n = 26); no mutation was revealed, but we did find a germline mutation in a PJS patient. Despite high LOH fiequencies at the 19p13.3 locus in carcinoma metastases to the brain and occasional mutations reported for certain primary carcinomas, there are no mutations in LKB1/STK11. This fact suggests that alterations of LKB1/STK11 occur relatively early in tumorigenesis and are rarely involved in the development of carcinoma metastases. Based on these findings, the genes adjacent to LKB1/STK11 may be relevant for the development of metastases to the brain from certain carcinomas.

AMP-Activated Protein Kinase Kinases↗
PubMed2000

Down-regulation of SP1 DNA binding activity in the process of radiation-induced pulmonary fibrosis.

PURPOSE: To determine changes in the expression and function of the transcription factor SP1 in radiation-induced pulmonary fibrosis. MATERIALS AND METHODS: The right lungs of female Fischer rats were irradiated with a fibrogenic single dose of 20 Gy gamma-irradiation. SP1 mRNA and protein expression was determined by Northern and Western blotting, respectively, between 30 min and 12 weeks after irradiation. Cellular localization of SP1 protein was characterized by immunohistochemistry (peroxidase labelling). SP1 DNA binding activity was studied with electrophoretic mobility shift assays (EMSA). RESULTS: Eight weeks after irradiation, pulmonary fibrosis was first observed. SP1 DNA binding activity showed a short-term increase from 30 min to 12 h after irradiation. Thereafter it remained quite stable until 1 month after irradiation. However, 2 months after irradiation, SP1 DNA binding activity was no longer detectable. The SP1 mRNA level was not reduced at this time, nor was there a reduction in its size. However, Western blotting revealed the occurrence of at least two slightly smaller additional bands 2 months after irradiation whereas the original SP1 band vanished. This suggests a degradation event of SP1 taking place near one or both ends of the protein. Most of the SP1 protein was found in type II pneumocytes and alveolar macrophages of the normal and fibrotic lung. Bronchial epithelial cells were also positive. In the fibrotic lung, proliferating fibroblasts also become positive. CONCLUSIONS: The functional knockout of the transcription factor SP1, in the process of irradiation-induced pulmonary fibrosis, is demonstrated. This should help elucidate the severe disturbances in transcriptional regulation, cellular proliferation and differentiation occurring in the lung at long intervals after irradiation.

Animals↗
PubMed2000

The complement regulators C1 inhibitor and soluble complement receptor 1 attenuate acute lung injury in rabbits.

Because activation of the complement system plays a major role in the pathogenesis of acute lung injury, the availability of new specific complement inhibitors represents a promising therapeutic approach. In the present study we investigated pulmonary edema formation and pulmonary artery pressure (PAP) in acute complement-induced lung injury for possible therapeutic impact of the complement regulators C1 inhibitor and soluble complement receptor 1. Eighteen isolated and ventilated rabbit lungs were perfused with pooled normal human serum (NHS, final concentration 35%) in Krebs-Henseleit buffer in a recirculating system. Lung weight gain and PAP were continuously recorded. Complement activation was blocked by the addition of C1 inhibitor (1.0 U/mL, n = 6) or sCR 1 (2.0 microg/mL, n = 6). Lungs that received NHS without inhibitors served as controls (n = 6). This study was performed according to the Helsinki Declaration and approved by the local government. Application of NHS resulted in an increase of PAP within 20 min from 8+/-2 to 42+/-6 mmHg, which was significantly (P < 0.05) decreased by C1-Inh (25+/-5 mmHg) and sCRI (20 +/-3 mmHg). Moreover, pulmonary edema formation after NHS, as assessed by overall weight gain, was reduced by both C1-Inh and sCR1, compared with controls. These findings were paralleled with significantly decreased thromboxane release rates and reduced tissue deposition of C3c and C5b-9. C1 inhibitor and sCR1 attenuate the complement-induced pulmonary capillary leakage and PAP increase, indicating the protective effect of complement inhibition in isolated perfused rabbit lungs.

Animals↗
PubMed1999

Differential immunolocalization of VEGF in rat and human adult lung, and in experimental rat lung fibrosis: light, fluorescence, and electron microscopy.

Vascular endothelial growth factor (VEGF) is a cytokine with main angiogenetic functions in embryonic development and tumor-formation. In the adult lung, reports of the localization of VEGF were controversial. A precise cell typing of VEGF-positive pulmonary cells is still lacking. Nothing is known about a potential role in pulmonary fibrosis. Immunohistochemistry (IH), double immunofluorescence microscopy (DIF), and immunoelectron microscopy (IEM) were used to study the differential distribution of VEGF in paraffin-embedded (IH, DIF) and in cryo-substituted, Lowicryl-embedded (IEM) specimens of normal rat and human lungs and fibrotic rat lungs. Fibrosis was induced by intratracheal bleomycin treatment. IH and DIF showed that VEGF was present in surfactant protein (SP) D-positive alveolar type II pneumocytes, bronchiolar Clara cells, smooth muscle (SM) cells, and alpha-SM actin-positive myofibroblasts of normal rat and human lungs. Fibrotic lesions in bleomycin-treated rat lungs were rich in VEGF-positive cells presenting with a heterogeneous phenotype (mainly SP-D-positive type II pneumocytes, alpha-SM actin-positive myofibroblasts). There were no signs of angiogenesis. Post-embedding immunogold labeling using protein A-gold and IgG-gold technique revealed a specific localization of VEGF to mitochondria, Clara cell secretory granules, and capillary interendothelial cell junctions. The predominant localization of VEGF to bronchiolar and alveolar epithelial and alpha-SM actin-positive cells, and the marked increase of VEGF-positive type II pneumocytes and myofibroblasts in fibrotic lung lesions, indicate that in adult lungs VEGF is involved in processes other than angiogenesis.

Adult↗
PubMed1999

Response of pig lung to irradiation with accelerated 12C-ions.

The response of pig lungs to irradiation with 12C-ions was assessed in two experiments to validate the procedures for heavy ion therapy planning at the Gesellschaft für Schwerionenforschung (GSI) and to explore their range of applicability. In both experiments, the target volume (spread-out Bragg peak, SOBP) was planned to be a 4 cm long cylinder with a diameter of 4 cm. Doses in the SOBP were prescribed to be equivalent to 5x4 Gy, 5x5.5 Gy and 5x7 Gy of x-rays in the first experiment, and to 5 fractions of 7 Gy and 9 Gy in the second experiment. The lung response in the first experiment was less than expected on the basis of earlier experiments with photons. Pneumonitis reaction and chronic fibrotic changes were observed outside the prescribed high-dose region. In the second experiment, the effects were more pronounced than had been expected on the basis of the first experiment. Changes were most intense in the high-dose region, but were also seen throughout the lung along the beam channel. Moreover, significant skin reactions were observed at the beam entrance site in all animals and - less pronounced - at the beam exit site in 3 of the 6 animals. In conclusion, the complex irradiation geometry of the pig lung, the changes of body weight between the two experiments, and insufficient accounting for a change in the relative biological effectiveness (RBE) computation led to substantial deviations of the observed reactions from expectations, the reasons for which could be identified in a subsequent analysis. The less pronounced lung reaction in the first experiment was due to an overestimation of RBE in a preliminary version of the algorithm for its determination. The extension of the fibrotic reaction resulted from the smear-out of the high-dose region due to density variations in tissue structures, respiratory movement, and limited positioning accuracy. The skin reactions at the entrance port reflect the different treatment geometry in the two experiments. The one unexplained observation is the mild skin reaction that was observed in the second experiment at the beam exit site.

Animals↗
PubMed1999

Alterations in the immunohistochemical distribution patterns of vascular endothelial growth factor receptors Flk1 and Flt1 in bleomycin-induced rat lung fibrosis.

To investigate the role of vascular endothelial growth factor (VEGF) in fibrogenesis, the distribution patterns of the VEGF receptors Flt1 and Flk1 were studied by immunohistochemistry, double immunofluorescence, and immunoelectron microscopy in normal (n=2) and bleomycin-treated (n=21) adult rats. Lungs were studied at 5, 24, 28, 35, and 42 days after treatment (p.t.). Flt1, Flk1, and VEGF immunoreactivity localised predominantly to the pulmonary epithelium. In control lungs, Flt1 immunoreactivity was present in ciliated bronchial epithelium and type 2 pneumocytes, Flk1 in Clara cells, and VEGF in Clara cells and type 2 pneumocytes. Flk1 localised to mast cells, present in the peribronchovascular and pleural interstitium only. Flt1- and Flk1-mRNAs were observed in Clara cells and type 2 pneumocytes. Bleomycin-induced fibrogenesis was characterised by a decrease in Flk1 immunoreactivity of Clara cells, and an increase in VEGF-immunoreactive myofibroblasts and type 2 pneumocytes by day 5 p.t., followed by a progressive accumulation of Flk1-immunoreactive mast cells by day 24 p.t. in fibrotic lesions containing VEGF-immunoreactive myofibroblasts. After 42 days, fibrotic regions were densely populated by mast cells. Since mast cells are known to be chemotactically attracted by VEGF, we suggest that VEGF/Flk1 represents the molecular link between proliferation of myofibroblasts, accumulation of mast cells, and the burst of fibrosis at sites of initial lesions in bleomycin-induced fibrosis.

Animals↗
PubMed1999

Locally recurrent malignant fibrous histiocytoma: a rare and aggressive genitourinary malignancy.

OBJECTIVE: In this study, 22 cases of locally recurrent urological malignant fibrous histiocytoma were reviewed considering therapeutic options, follow-up and prognosis. PATIENTS AND METHODS: In the available literature on this topic we identified 19 cases of locally recurrent genitourinary malignant fibrous histiocytoma. Three additional cases are discussed, primarily arising from the kidney, the bladder and the paratesticular region. RESULTS: The prognosis of locally recurrent urological malignant fibrous histiocytoma was found to be extraordinarily poor. Only 2 of 22 patients have survived for longer than 3.5 years. One of them reported herein is still alive 10 years after extensive lymphatic spread accompanying the first local recurrence. In this case, late local recurrence occurred after an 8-year interval free of disease. CONCLUSION: Malignant fibrous histiocytoma is an unusual urological malignancy with a high rate of local recurrence. The latter is frequently accompanied by metastatic disease and unrelenting progression. Despite the poor prognosis early detection of local failure and aggressive salvage therapy might offer the chance of long-term survival in selected cases. Close and life-long follow-up is advisable for patients once treated for recurrent urological malignant fibrous histiocytoma.

Aged↗
PubMed1999

Physician practice management organizations: their prospects and performance.

As physician organizations adapt their incentives, processes, and structures to accommodate the demands of an increasingly competitive and performance-sensitive external environment, the development of more effective administrative and managerial mechanisms becomes critical to success. The emergence of physician practice management companies (PPMCs) represents a potentially positive step for physician practices seeking increased economies of scale through consolidation, as well as enhanced access to financial capital. However, economic and finance theory, coupled with some empirical "arithmetic" regarding the financial and operational performance of leading publicly traded PPMCs, suggest caution in one's forecasts of the future prospects for these evolving corporate forms.

Contract Services↗