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M Wendland

Publications and source records attributed to M Wendland.

At least 19 recordsLinked to original sources
PubMed2006

[MRI of arthritis with the USPIO SH U 555 C: optimization of T1 enhancement].

PURPOSE: To optimize contrast agent dose and pulse sequence parameters in order to achieve a maximal T1 enhancement in arthritic knee joints with ultra small superparamagnetic iron oxides (USPIO)-enhanced MRI. MATERIALS AND METHODS: Antigen-mediated arthritis was induced in the right knee of nine Sprague Dawley rats. The arthritic knee joint as well as the contralateral normal knee were investigated in a 2 Tesla MR scanner before as well as in short intervals up to 2 h after USPIO injection, using T1-weighted gradient echo (GE) sequences. Three rats each received intravenous injections of the new USPIO SHU 555 C (SH U 555 C, Schering AG, Berlin) at doses of 40, 100 and 200 micromol Fe/kg. Pulse sequence parameters of the GE-sequence were optimized by varying flip angles (alpha) and echo times (TE). Changes in signal intensities (SI) of the arthritic knee and contralateral normal knee were quantified as DeltaSI (%) = /([SIpost - SIpre] / SIpre) x 100 %/ and compared with histopathology. RESULTS: Histology of the arthritic knees demonstrated a marked inflammatory proliferation of the synovium. The USPIO SH U 555 C caused a significant increase in signal intensity of the arthritic joints on T1-weighted MR images (p < 0.05). This effect was optimized using a flip angle of 60-70 degrees, a minimal TE and a dose of 200 micromol Fe/kg. Visually the contralateral normal knee did not show any USPIO enhancement. CONCLUSION: Inflammation can be depicted with marked T1 enhancement by the USPIO SH U 555 C using high contrast agent doses and optimized MR pulse sequence parameters.

Animals↗
PubMed2006

Comparison of microvascular permeability measurements, K(trans), determined with conventional steady-state T1-weighted and first-pass T2*-weighted MR imaging methods in gliomas and meningiomas.

BACKGROUND AND PURPOSE: The widely accepted MR method for quantitating brain tumor microvascular permeability, K(trans), is the steady-state T1-weighted gradient-echo method (ssT1). Recently the first-pass T2*-weighted (fpT2*) method has been used to derive both relative cerebral blood volume (rCBV) and K(trans). We hypothesized that K(trans) derived from the ssT1 and the fpT2* methods will correlate differently in gliomas and meningiomas because of the unique differences in morphologic and functional status of each tumor vascular network. METHODS: Before surgery, 27 patients with newly diagnosed gliomas (WHO grade I-IV; n = 20) or meningiomas (n = 7) underwent conventional anatomic MR imaging and 12 dynamic ssT1 acquisitions followed by 60 dynamic fpT2* images before and after gadopentate dimeglumine administration. The 3 hemodynamic variables-fpT2* rCBV, fpT2* K(trans), and ssT1 K(trans)-were calculated in anatomically identical locations and correlated with glioma grade. The fpT2* K(trans) values were compared with ssT1 K(trans) for gliomas and meningiomas. RESULTS: All 3 hemodynamic variables displayed distinct distributions among grades 2, 3, and 4 gliomas by using the Kruskal-Wallis test. Only K(trans) values, and not rCBV, could differentiate between grade 4 and lower-grade gliomas by using the Wilcoxon rank sum test. The fpT2* K(trans) was highly predictive of ssT1 K(trans) for gliomas, with an estimated regression coefficient of 0.49 (P < .001). For meningiomas, however, fpT2* K(trans) values correlated poorly with ssT1 K(trans) values (r = 0.26; P = .74). CONCLUSION: Compared with rCBV, K(trans) values derived from either ssT1 or fpT2* were more predictive of glioma grade. The fpT2* K(trans) was highly correlated with ssT1 K(trans) in gliomas but not in meningiomas.

Adolescent↗
PubMed2003

Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23.

The orphan receptor ChemR23 is a G-protein coupled receptor (GPCR) with homology to neuropeptide and chemoattractant receptors. Tazarotene, a synthetic retinoid activating retinoic acid receptor (RAR), up-regulates tazarotene-induced gene-2 (TIG2). The function and molecular target of this protein are now described. By means of reverse pharmacology screening using a peptide library generated from human hemofiltrate, we have isolated and identified TIG2 as the natural ligand of ChemR23 and report the specific molecular form of the bioactive, circulating TIG2, representing the amino-acid residues 21 to 154 of the 163 amino acid-containing prepropeptide. Based on the expression pattern of ChemR23 and TIG2, the physiological role in bone development, immune and inflammatory responses and the maintenance of skin is now being investigated.

Amino Acid Sequence↗
PubMed2003

Reperfusion differentially induces caspase-3 activation in ischemic core and penumbra after stroke in immature brain.

BACKGROUND AND PURPOSE: Different strategies for neuroprotection of neonatal stroke may be required because the developing brain responds differently to hypoxia-ischemia than the mature brain. This study was designed to determine the role of caspase-dependent injury in the pathophysiology of pure focal cerebral ischemia in the immature brain. METHODS: Postnatal day 7 rats were subjected to permanent or transient middle cerebral artery (MCA) occlusion. Diffusion-weighted MRI was used during occlusion to noninvasively map the evolving ischemic core. The time course of caspase-3 activation in ischemic brain tissue was determined with the use of an Asp-Glu-Val-Asp-aminomethylcoumarin cleavage assay. The anatomy of caspase-3 activation in the ischemic core and penumbra was mapped immunohistochemically with an anti-activated caspase-3 antibody in coronal sections that matched the imaging planes on diffusion-weighted MRI. RESULTS: A marked increase in caspase-3 activity occurred within 24 hours of reperfusion after transient MCA occlusion. In contrast, caspase-3 activity remained significantly lower within 24 hours of permanent MCA occlusion. Cells with activated caspase-3 were prominent in the penumbra beginning at 3 hours after reperfusion, while a more delayed but marked caspase-3 activation was observed in the ischemic core by 24 hours after reperfusion. CONCLUSIONS: In the neonate, caspase-3 activation is likely to contribute substantially to cell death not only in the penumbra but also in the core after ischemia with reperfusion. Furthermore, persistent perfusion deficits result in less caspase-3 activation and appear to favor caspase-independent injury.

Animals↗
PubMed2001

Safety and immunogenicity of live recombinant Salmonella enterica serovar Typhi Ty21a expressing urease A and B from Helicobacter pylori in human volunteers.

Helicobacter pylori urease was expressed in the common live typhoid vaccine Ty21a yielding Ty21a(pDB1). Nine volunteers received Ty21a(pDB1) and three control volunteers received Ty21a. No serious adverse effects were observed in any of the volunteers. Ten out of 12 volunteers developed humoral immune responses to the Salmonella carrier as detected by antigen-specific antibody-secreting cells but only two volunteers seroconverted. A total of five volunteers showed responses in one or two out of three assays for cellular responses to the carrier (proliferation, IFN-gamma-secretion, IFN-gamma-ELISPOT). Three of the volunteers that had received Ty21a(pDB1) showed a weak but significant T-cell response to Helicobacter urease, while no volunteer had detectable humoral responses to urease. Ty21a(pDB1) is a suitable prototype to optimize Salmonella-based vaccination for efficient cellular responses that could mediate protective immunity against Helicobacter.

Adolescent↗
PubMed2000

Comparison of Gadomer-17 and gadopentetate dimeglumine for differentiation of benign from malignant breast tumors with MR imaging.

RATIONALE AND OBJECTIVES: This study compared gadopentetate dimeglumine (molecular weight, 0.5 kD), a standard contrast medium, and Gadomer-17 (apparent molecular weight, approximately 35 kD), a new, clinically applicable, large-molecular contrast medium, with respect to their microvascular characterizations of experimentally induced breast tumors at magnetic resonance (MR) imaging. MATERIALS AND METHODS: A spectrum of breast tumors, benign through highly malignant, was induced in Sprague-Dawley rats (n = 30) by intraperitoneal administration of N-ethyl-N-nitrosourea (ENU), a potent carcinogen. All animals underwent three-dimensional spoiled gradient-recalled MR imaging, with precontrast imaging and dynamic postcontrast imaging after injection of gadopentetate dimeglumine (0.1 mmol/kg) and Gadomer-17 (0.03 mmol/kg), administered in a random order at a 24-hour interval. Several microvascular parameters were compared: the endothelial transfer coefficient (K(PS)), a measure of microvascular permeability; the fractional plasma volume (fPV), and the plasma equivalent volume. Each MR imaging parameter was correlated with histopathologic findings. RESULTS: With Gadomer-17, the mean values for K(PS) and fPV were significantly greater in carcinomas than in fibroadenomas (P < .004 and .04, respectively). With gadopentetate dimeglumine, the mean values for fPV and PEV were significantly greater in carcinomas (P <. 004 and .02, respectively). Because of the high variability within both fibroadenoma and carcinoma groups, however, there were no significant correlations between K(PS), fPV, or PEV and histopathologic tumor grade as indicated by the Scarff-Bloom-Richardson score, for either agent. CONCLUSION: Although the K(PS) and fPV estimates obtained from dynamic MR imaging data with Gadomer-17 enhancement offer some potential for characterizing breast tumors, none of the quantitative microvascular parameters derived with either agent were significantly correlated with histopathologic tumor grade.

Animals↗
PubMed2000

Evolution of brain injury after transient middle cerebral artery occlusion in neonatal rats.

BACKGROUND AND PURPOSE: Stroke in preterm and term babies is common and results in significant morbidity. The vulnerability and pathophysiological mechanisms of neonatal cerebral ischemia-reperfusion may differ from those in the mature cerebral nervous system because of the immaturity of many receptor systems and differences in metabolism in neonatal brain. This study details the neuropathological sequelae of reperfusion-induced brain injury after transient middle cerebral artery (MCA) occlusion in the postnatal day 7 (P7) rat. METHODS: P7 rats were subjected to 3 hours of MCA occlusion followed by reperfusion or sham surgery. Diffusion-weighted MRI was performed during MCA occlusion, and maps of the apparent diffusion coefficient (ADC) were constructed. Contrast-enhanced MRI was performed in a subset of animals before and 20 minutes after reperfusion. Triphenyltetrazolium chloride (TTC) staining of the brain was performed 24 hours after reperfusion. Immunohistochemistry to identify astrocytes (glial fibrillary acidic protein), reactive microglia (ED-1), and neurons (microtubule-associated protein 2) and cresyl violet staining were done 4, 8, 24, and 72 hours after reperfusion. RESULTS: On contrast-enhanced MRI, nearly complete disruption of cerebral blood flow was evident in the vascular territory of the MCA during occlusion. Partial restoration of blood flow occurred after removal of the suture. A significant decrease of the ADC, indicative of early cytotoxic edema, occurred in anatomic regions with a disrupted blood supply. The decline in ADC was associated with TTC- and cresyl violet-determined brain injury in these regions 24 hours later. The ischemic core was rapidly infiltrated with reactive microglia and was surrounded by reactive astroglia. CONCLUSIONS: In P7 rats, transient MCA occlusion causes acute cytotoxic edema and severe unilateral brain injury. The presence of a prominent inflammatory response suggests that both the ischemic episode and the reperfusion contribute to the neuropathological outcome.

Animals↗
PubMed1999

The adeno-associated virus type 2 regulatory proteins rep78 and rep68 interact with the transcriptional coactivator PC4.

The adeno-associated virus type 2 (AAV-2) Rep78/Rep68 regulatory proteins are pleiotropic effectors of viral and cellular DNA replication, of cellular transformation by viral and cellular oncogenes, and of homologous and heterologous gene expression. To search for cellular proteins involved in mediating these functions, we used Rep68 as bait in the yeast two-hybrid system and identified the transcriptional coactivator PC4 as a Rep interaction partner. PC4 has been shown to mediate transcriptional activation by a variety of sequence-specific transcription factors in vitro. Rep amino acids 172 to 530 were sufficient and amino acids 172 to 224 were absolutely necessary for the interaction with PC4. The PC4 domains required for interaction were mapped to the C-terminal single-stranded DNA-binding domain of PC4. In glutathione S-transferase (GST) pull-down assays, in vitro-transcribed and -translated Rep78 or Rep68 proteins were bound specifically by GST-PC4 fusion proteins. Similarly, PC4 expressed in Escherichia coli was bound by GST-Rep fusion proteins, confirming the direct interaction between Rep and PC4 in vitro. Rep was found to have a higher affinity for the nonphosphorylated, transcriptionally active form of PC4 than for the phosphorylated, transcriptionally inactive form. The latter is predominant in nuclear extracts of HeLa or 293 cells. In the yeast system, but not in vitro, Rep-PC4 interaction was disrupted by a point mutation in the putative nucleotide-binding site of Rep68, suggesting that a stable interaction between Rep and PC4 in vivo is ATP dependent. This mutation has also been shown to impair Rep function in AAV-2 DNA replication and in inhibition of gene expression and inducible DNA amplification. Cytomegalovirus promoter-driven overexpression of PC4 led to transient accumulation of nonphosphorylated PC4 with concomitant downregulation of all three AAV-2 promoters in the absence of helper virus. In the presence of adenovirus, this effect was relieved. These results imply an involvement of the transcriptional coactivator PC4 in the regulation of AAV-2 gene expression in the absence of helper virus.

Base Sequence↗
PubMed1998

p16/INK4a and p15/INK4b gene methylation and absence of p16/INK4a mRNA and protein expression in Burkitt's lymphoma.

The fact that the p16/INK4a and p15/INK4b genes are frequently inactivated in human malignancies and that p16/INK4a null mice spontaneously develop B-cell lymphomas prompted us to examine the status of both genes in Burkitt's Lymphoma (BL). We found a low frequency of p16/INK4a and p15/INK4b deletions and mutations in BL cell lines and biopsies. However, p16/INK4a exon 1 was methylated in 17 out of 19 BL lines (89.5%) and in 8 out of 19 BL biopsies (42%) analyzed. p15/INK4b Exon 1 was also methylated, although at a lower frequency. p16/INK4a mRNA was readily detected in BL lines carrying unmethylated p16/INK4a, but not in those carrying methylated p16/INK4a. No p16/INK4a protein was detected in any of the BL lines and biopsies examined. In contrast, only one out of seven lymphoblastoid cell lines (LCLs) examined was methylated in p16/INK4a exon 1, and three out of the six LCLs with unmethylated p16/INK4a expressed detectable levels of p16/INK4a protein. Thus, the frequent p16/INK4a methylation in BL lines correlates with downregulation of p16/INK4a expression, suggesting that exon 1 methylation is responsible for silencing the p16/INK4a gene in BL.

Blotting, Northern↗
PubMed1998

Correlation of dynamic contrast-enhanced magnetic resonance imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media.

BACKGROUND: The endothelial integrity of microvessels is disrupted in malignant tumors. Quantitative assays of tumor microvascular characteristics based on dynamic magnetic resonance imaging (MRI) were correlated with histopathologic grade in mammary soft tissue tumors. MATERIALS AND METHODS: A spectrum of tumors, benign through highly malignant, was induced in 33 female rats by administration of N -ethyl-N -nitrosourea (ENU), a potent carcinogen. Dynamic contrast-enhanced MRI was performed using a small-molecular contrast medium [gadopentetate, MW = 0.5 kDa] and a macromolecular contrast medium [albumin-(Gd-DTPA)30, MW = 92 kDa] at an interval of 1-2 days. Permeability surface area product (PS), as estimated by the corresponding endothelial transfer coefficient (KPS), and fractional plasma volume (fPV) were calculated for each tumor and each contrast agent using a two-compartment bi-directional kinetic model. MRI microvascular characteristics were correlated with histopathologic tumor grade. RESULTS: Tumor permeability to macromolecular contrast medium, characterized by KPS, showed a highly positive correlation with tumor grade (r 2 = 0.76, P < 10(-10)). KPS values were zero for all benign and some low-grade carcinomas, greater than zero in all other carcinomas, and increased in magnitude with higher tumor grade. A considerably smaller but significantly positive correlation was found between fPV and tumor grade using macromolecular contrast medium (r 2 = 0.25, P < 0.003). No correlation between KPS or fPV values and tumor grade was found using gadopentetate (r 2 = 0.01, P > 0.95 and r2 = 0.03, P > 0.15, respectively). CONCLUSION: Quantitative tumor microvascular permeability assays generated with macromolecular MRI contrast medium correlate closely with histologic tumor grade. No significant correlation is found using small-molecular gadopentetate.

Albumins↗
PubMed1998

Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media.

OBJECTIVE: The endothelial integrity of microvessels is disrupted in malignant tumors. Quantitative assays of tumor microvascular characteristics based on dynamic MR imaging were correlated with histopathologic grade in mammary soft-tissue tumors. MATERIALS AND METHODS: A spectrum of tumors, benign through highly malignant, was induced in 33 female rats by administration of N-ethyl-N-nitrosourea, a potent carcinogen. Dynamic contrast-enhanced MR imaging was performed using a small-molecular contrast medium (gadopentetate, molecular weight = 0.5 kDa) and a macromolecular contrast medium (albumin-(Gd-DTPA)30, molecular weight = 92 kDa) at an interval of 1-2 days. Permeability surface area product (PS), as estimated by the corresponding endothelial transfer coefficient (K(PS)), and fractional plasma volume (fPV) were calculated for each tumor and each contrast agent using a two-compartment bidirectional kinetic model. MR imaging microvascular characteristics were correlated with histopathologic tumor grade. RESULTS: Tumor permeability to macromolecular contrast medium, characterized by K(PS), showed a highly positive correlation with tumor grade (r2 = .76, p < 10(-10)). K(PS) values were zero for all benign and some low-grade carcinomas, greater than zero in all other carcinomas, and increased in magnitude with higher tumor grade. A considerably smaller but significantly positive correlation was found between fPV and tumor grade using macromolecular contrast medium (r2 = .25, p < .003). No correlation between K(PS) or fPV values and tumor grade was found using gadopentetate (r2 = .01, p > .95 and r2 = .03, p > .15, respectively). CONCLUSION: Quantitative tumor microvascular permeability assays generated with macromolecular MR imaging contrast medium correlate closely with histologic tumor grade. No significant correlation is found using small-molecular gadopentetate.

Albumins↗
PubMed1997

[Macromolecular contrast media for MR mammography. A new approach to characterizing breast tumors].

The value of macromolecular contrast agents (MMCM) for the characterization of benign and malignant breast tumors will be demonstrated in this review. Animal studies suggest a high potential of MMCM to increase the specificity of MR-mammography. The concept of tumor differentiation is based on the pathological hyperpermeability of microvessels in malignant tumors. MMCM show a leak into the interstitium of carcinomas, whereas they are confined to the intravascular space in benign tumors. Capabilities and limitations of the MMCM-prototype. Albumin-Gd-DTPA, for breast tumor characterization will be summarized and compared to the standard low molecular weight contrast agent Gd-DTPA. Initial experience with new MMCM, such as Dendrimers, Gd-DTPA-Polylysine and MS-325 will be outlined. The potential of "blood-pool"-iron oxides, such as AMI-227 for the evaluation of tumor microvascular permeabilities will be discussed.

Breast↗
PubMed1997

Quantification of area at risk during coronary occlusion and reperfusion by means of MR perfusion imaging.

PURPOSE: Considerable clinical interest has focused on the size of ischemic myocardium. Fast MR imaging in conjunction with MR contrast media has the potential to identify hypoperfused and infarcted myocardium. This study used MR perfusion imaging to detect and quantify reperfused ischemic myocardium during a brief coronary occlusion and reperfusion, and to characterize the spatial extent of ischemic and reperfused ischemic myocardium relative to the "true" size of the area at risk as defined in histochemical morphometry at post mortem. MATERIAL AND METHODS: The left circumflex (LCX) coronary artery in 8 dogs was occluded for 15 min followed by reperfusion in order to produce regional reversible myocardial ischemia. Perivascular Doppler probes were used to measure blood flow in the left anterior descending (LAD) and LCX coronary arteries. Fast inversion recovery-prepared gradient-recalled-echo images were acquired to delineate the ischemic area during occlusion, and the area of reversible ischemic injury at 1 and 30 min of reperfusion. The size of ischemic and reperfused ischemic myocardium were compared with the area at risk as determined by histochemical morphometry at post mortem. RESULTS: During LCX occlusion, LCX flow decreased from 16+/-1 to 0.2+/-0.1 ml/min. On contrast-enhanced images, ischemic myocardium was evident as a zone of relatively low signal intensity (SI) compared to normal myocardium. The size of the ischemic region was significantly smaller (30+/-2%) than at post mortem (36+/-3%; p<0.05). Immediately after reperfusion, LCX flow increased to 83+/-11 ml/min and the contrast medium caused greater enhancement in the reperfused ischemic region than in the normal myocardium (69+/-3 vs 42+/-3 arbitrary units; p<0.05). The increase in regional SI correlated closely with the increase in regional blood flow (r=0.73). At 1 min of reperfusion, the size of the reperfused ischemic myocardium was larger (48+/-3%, p<0.05) than the area at risk measured at post mortem. At 30 min of reperfusion, when the flow returned to baseline values (16+/-2 ml/min), contrast bolus produced no differential enhancement between the 2 myocardial territories. CONCLUSION: MR perfusion imaging has the potential to detect and quantify the size of ischemic myocardium and the region of post-occlusive hyperemia in the early reperfusion period. There is a significant direct linear relationship between the regional contrast enhancement of reperfused ischemic myocardium and the blood flow during post-occlusive hyperemia. The difference in the size of the area at risk at MR perfusion imaging and at histochemical morphometry may reflect an influence of coronary collateral circulation.

Animals↗
PubMed1997

Proteolysis of insulin-like growth factors (IGF) and IGF binding proteins by cathepsin D.

Various proteinases have been postulated to function in limited proteolysis of insulin-like growth factor binding proteins (IGFBPs) contributing to the regulation of IGF bioavailability. In this study, we report on the in vitro degradation of IGFs and IGFBPs by the purified acidic aspartylprotease cathepsin D that has been shown to proteolyze IGFBP-3. Recombinant human [125I] IGFBP-1 to -5 were processed by cathepsin D to fragments of defined sizes in a concentration dependent manner, whereas IGFBP-6 was not degraded. Ligand blotting revealed that none of the IGFBP-1 or -3 fragments formed by cathepsin D retain their ability to bind IGF. By N-terminal sequence analysis of nonglycosylated IGFBP-3 fragments produced by cathepsin D, at least four different cleavage sites were identified. Some of these cleavage sites were identical or differed by one amino acid from sites used by other IGFBP proteases described. The IGFBP-3 and -4 cleavage sites produced by cathepsin D are located in the nonconserved central region. IGF-I and -II, but not the unrelated platelet-derived growth factor BB, were degraded by cathepsin D in a time and concentration-dependent manner. We speculate that the major functional site of cathepsin D is intracellular and may be involved 1) in the selected clearance either of IGFBP or IGFs via different endocytic pathways or 2) in the general lysosomal inactivation of the IGF system.

Amino Acid Sequence↗
PubMed1996

[Low molecular weight heparin (Fraxiparine) as adjunctive therapy with thrombolysis for acute myocardial infarction: a pilot study with a one year follow up].

In 53 patients with recent (< 6 hrs) acute myocardial infarction a study was undertaken to evaluate the safety of conjunctive therapy with streptokinase (1.5 mln U), aspirin (150 mg) and low molecular weight heparin (Fraxiparine). Patients were treated with Fraxiparine 250 U anti-Xa IC/kg/24 hrs iv for 2 days (with bolus 12.5 U anti-Xa IC/kg), and 125 U anti-Xa IC/kg twice a day sc for 5 subsequent days. Clinical course in one-year observation was compared regarding the time the therapy was initiated. In the group undergoing therapy 3-6 hrs after the infarct had occurred 4 (7.5%) patients died (2 during hospitalization, 2 after discharge). In 31 patients treated within 3 hrs of the myocardial infarction there were fewer cases of recurrent myocardial infarction, unstable angina or congestive heart failure necessitating rehospitalization their (9.1%) than in 22 patients included in the treatment regimen between 3 rd and 6th h of the infarction (27.3%). Earlier thrombolysis was also connected with higher left ventricular ejection fraction (55 +/- 8% vs 49 +/- 10%) and more frequent peak CK-MB values 12 hrs after thrombolysis (81% and 68% of patients respectively). Neither symptomatic deep vein thrombosis nor pulmonary embolism was detected. The left ventricular thrombosis was diagnosed by echocardiography in 4 of 20 patients (20%) with the first anterior myocardial infarction. There was neither bleeding requiring blood transfusion nor cerebrovascular stroke. The treatment with Fraxiparine did not induce the prolongation of APTT values. Conjunctive thrombolytic therapy with low molecular weight heparin was safe and followed by a favorable outcome of the acute myocardial infarction, especially if instituted within the first 3 hrs after the onset of infarction.

Adult↗
PubMed1995

Proteolysis of IGFBPs by cathepsin D in vitro and in cathepsin D-deficient mice.

Affinity-purified lysosomal protease cathepsin D cleaved recombinant human IGFBP-1 to -5 in fragments of defined sizes, while IGFBP-6 was not degraded. To assess the role of cathepsin D for proteolytic processing of IGFBP in vivo, serum from cathepsin D-deficient mice and conditioned media from cathepsin D-deficient fibroblasts and organ explants were analyzed. No differences for the pattern and level of IGFBPs were detected. When conditioned media from fibroblasts were incubated at acid pH, proteolysis of IGFBP-1 and -4 was observed only in media derived from cathepsin D-expressing cells. Additional experiments showed that the proteolysis of IGFBP-4 is mediated by cathepsin D and not by a protease activated by cathepsin D. The IGFBP-4 degrading activities in media from organ explants from cathepsin D-deficient mice were found to be sensitive to inhibitors of aspartyl and cysteine proteases. The data indicate that different classes of acid pH-dependent proteases can contribute to the regulation of IGFBP-4 abundance.

Animals↗