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Biomedical subjects

M Engel

Publications and source records attributed to M Engel.

At least 37 records · Page 2Linked to original sources
PubMed1998

Role of transforming growth factor (TGF)-beta Type I and TGF-beta type II receptors in the TGF-beta1-regulated gene expression in pituitary prolactin-secreting lactotropes.

Transforming growth factor beta1 (TGF-beta1) inhibits pituitary lactotrope proliferation and secretion of PRL in an autocrine/paracrine manner. In this study, the role of TGF-beta1 type I (TbetaR-I) and TGF-beta type II (TbetaR-II) receptors in TGF-beta1-regulated gene expression in lactotropes was determined using anterior pituitary cells known to be responsive to TGF-beta1 growth inhibition and using a transformed PR1 cell line known to be nonresponsive to TGF-beta1 growth inhibition. Treatment with TGF-beta1 inhibited cell proliferation and decreased PRL mRNA levels in anterior pituitary cells, but in PR-1 cells, the treatment caused only decreased PRL mRNA levels. Affinity labeling of TGF-beta binding proteins indicated that anterior pituitary cells contain several TGF-beta-binding protein complexes, including the 65 kDa size TbetaR-I and 95 kDa size TbetaR-II. In the PR1 cells, the major complex found was similar to the 65 kDa size of TbetaR-I. Immunocytochemistry identified TbetaR-I and TbetaR-II receptor proteins in lactotropes but detected primarily TbetaR-I receptor protein in PR1 cells. RT-PCR detection of TbetaR-I and TbetaR-II mRNA identified both receptor mRNA transcripts in anterior pituitary cells and in PR1 cells but the levels of TbetaR-II and TbetaR-I mRNA transcripts in PR1 cells was much lower than that in anterior pituitary cells. Determination of the TGF-beta1 gene responses in PR1 cells following TbetaR-I and TbetaR-II gene transfection indicated that PR1 cells transactivate transcription of the TGF-beta-responsive p3TP-Lux reporter in the absence of cotransfected TbetaR-II receptor. The introduction of the TbetaR-II receptor alone or in combination with TbetaR-I confer ligand-independent reporter transactivation in these cells. When only TbetaR-I was introduced along with reporter, a ligand-dependent transactivation was observed. These data suggest for the first time that the TGF-beta1-mediated transcriptional activation response can be distinguished from the growth response in lactotropes. Furthermore, the TGF-beta1 gene-transcription response is less dependent on TbetaR-II receptor expression than is the TGF-beta1 growth-inhibitory response.

Activin Receptors, Type I↗
PubMed1997

Eradication of Aujeszky's disease virus from a Swedish pig herd using gI-/TK-vaccine.

An attenuated glycoprotein I-negative (gI-)/thymidine kinase-negative (TK-) constructed vaccine was used to eradicate Aujeszky's disease virus from a large farrow-to-finish herd in Sweden. The herd had had problems every year for seven years and two attempts to eradicate the virus without vaccination had failed. At the start of the vaccination programme 86 per cent of the 396 breeding animals were seropositive to the virus. In spite of evidence of virus circulation in the fattening units, no fatteners were vaccinated. The breeding stock was vaccinated every four months and monitored serologically. Seropositive sows and boars were culled at an economic rate. During the programme, four breeding animals seroconverted to gI. Another seven animals which seroconverted to gI were suspected to have been infected shortly before the first test and vaccination. When all the seropositive breeding animals had been culled, the fattening units were sampled and no seropositive animals were found. The herd was declared gI-negative 39 months after the start of the programme. Monitoring of the herd for another four years, until all the vaccinated animals had been culled, showed that the herd remained free from Aujeszky's disease virus.

Animals↗
PubMed1997

[Combined lytic and heart surgical therapy of in open foramen ovale incarcerated giant thrombus with pulmonary and cerebral embolization].

A case of phlebothrombosis with recurrent pulmonary and cerebral embolism is presented which occurred in a 42 year old patient two weeks after treatment of a traumatic crural fracture despite of prophylaxis with low molecular heparin. By means of transthoracic echocardiography a large intracardiac thrombus was detected, entrapped in an patent foramen ovale (PFO) and prolapsing through both atrioventricular valves into both ventricles. This was found after systemic thrombolysis with rtPA had been performed because of fulminant pulmonary embolism. Subsequently the intracardiac thrombus was surgically removed and the PFO closed. The importance of an PFO for paradoxical embolism is discussed as well as the various therapeutical paths to treat an "embolus-in-transit" (cardiac surgery, thrombolytic therapy or anti-coagulation).

Adult↗
PubMed1997

Isolation and characterization of new microsatellites at the nm23-H1 and nm23-H2 gene loci and application for loss of heterozygosity (LOH) analysis.

The nm23-H1 gene has been suggested to be a metastasis suppressor gene. Studies about the events of loss of heterozygosity (LOH) at the nm23 locus and its correlation to metastasis are controversially discussed. To optimize detection of LOH at the nm23 locus, we screened two P1 clones for additional microsatellites. Tumor and normal DNA from 37 colorectal, 16 gastric, and 8 germ cancer patients were examined for LOH. We found two new CA repeats, one 5' to nm23-H1 and another 3' to nm23-H2. Using these nm23 locus-specific CA repeats and five other chromosome 17 loci (D17S1522, D17S1566, D17S855, D17S515, and TP53), allele loss was observed in 4/32 (12.5%) patients with colon cancer, 2/14 (14.3%) with gastric cancer, and 1/7 (14%) with germ cancer. No isolated LOH of the nm23 region was observed.

Aged↗
PubMed1997

The development of drawing in children with congenital focal brain injury: evidence for limited functional recovery.

Children with pre- or perinatal injury to right hemisphere (RH) brain regions show impairment of spatial integrative functions similar to that observed among adults with comparable injury. Unlike adults, children show considerable improvement with development on a range of spatial construction tasks which require spatial integration. Such gains could reflect true recovery of spatial integrative abilities. Alternatively, the improvement could be more limited in scope, reflecting the development of compensatory strategies which are task specific and allow the children to circumvent, rather than overcome, their primary spatial disorders. The studies presented here examined this distinction within the context of drawing tasks in which the child was first asked to draw a house and then an impossible house. The impossible house task was designed to examine the extent to which children rely on graphic formulas in generating organized drawings. The results showed that while all of the children with RH injury make considerable progress in free drawing into the school age period, they are very reliant on the use of graphic formulas. When given a task which requires them to alter their drawings, they did not change the spatial configuration of the depicted object. Rather they found alternate ways to render the object 'impossible'.

Adolescent↗
PubMed1997

Expression of the candidate tumor suppressor gene nm23 in the bronchial system of patients with squamous cell lung cancer.

OBJECTIVE: A number of oncogenes and tumor suppressor genes participating in tumorigenesis have been identified, one of them being nm23. The expression of the candidate tumor suppressor gene nm23 depends on the cell type of tumors. Both, reduced expression as well as overexpression of nm23 is associated with a high potential of malignancy. In a variety of tumor cell lines secretion of the nm23 protein can be detected. In an earlier investigation we showed, that the nm23 expression in squamous cell lung carcinoma is considerably elevated. In order to establish the potential diagnostic value of this finding we investigated the nm23 expression in healthy and diseased lungs in patients with squamous cell lung cancers. METHODS: We examined bronchial lavage samples of 20 patients with bronchogenic squamous cell carcinoma. The lavage was separately performed in the bronchus of the tumor bearing lobe and in the corresponding bronchus of the unaffected contralateral lung. RESULTS: Using Western blot analysis we found 2-7 fold elevated amount of nm23 protein in bronchial lavage of the tumor bearing lung in comparison to the healthy side. This finding was neither related to tumor stage nor to tumor location. Thus we have a strong hint that the nm23 protein is secreted by the bronchogenic squamous cell carcinoma. CONCLUSIONS: With respect to these results the proof of nm23 protein in bronchial lavage fluid might be of relevance to establish the diagnosis when pulmonary nodules of unknown etiology are found.

Biomarkers, Tumor↗
PubMed1997

[Percutaneous embolization therapy in severe cervicofacial hemorrhages].

PURPOSE: To analyse the use of transcatheter embolisation. MATERIAL AND METHODS: We report on 43 patients treated by transcatheter embolisation for head and neck haemorrhage from 1987 to 1995. There were 13 patients with idiopathic intractable epistaxis, 6 with iatrogenic and three with traumatic bleeding, 7 patients with bleeding from vascular malformations, 12 patients with haemorrhage from tumours, one ruptured aneurysm of the inferior thyroid artery and one patient bleeding from a retrolingual dystrophic goitre. RESULTS: In 11/13 patients with idiopathic epistaxis, this could be stopped. In 8/9 of the traumatic and iatrogenic bleedings the haemorrhage was treated by embolisation alone. In two cases additional elective surgical interventions were necessary. In 6/7 patients with vascular malformations embolisation resulted in long-lasting periods free from bleeding. Palliative embolisation in bleeding tumours resulted in haemostasis in 10/12 patients. Bleeding was definitely stopped in a patient with aneurysm of the inferior thyroidal artery as well as in a patient with bleeding from a dystrophic goitre. We observed a total of three complications, two transitory neurological disturbances and one permanent amaurosis. CONCLUSION: Transcatheter embolisation is an effective tool in the treatment of life-threatening head and neck bleedings.

Acute Disease↗
PubMed1997

Nucleotide sequence evidence for the occurrence of three distinct whitefly-transmitted, Sida-infecting bipartite geminiviruses in Central America.

The nucleotide sequences of two Sida-infecting geminiviruses from Honduras were determined. The symptoms of both viruses are identical in Sida rhombifolia but different in Nicotiana benthamiana. An additional symptom of one virus was yellow vein clearing on infected N. benthamiana leaves. Both Sida golden mosaic viruses (SiGMV-Ho and SiGMV-Ho(yv)) have bipartite genomes (DNAs A and B). From the SiGMV-Ho(yv)-infected S. rhombifolia plant two different DNA B molecules were isolated and cloned. They differ in length by 24 nucleotides [SiGMV-Ho(yv) B1 (2593 nt) and B2 (2569 nt)] and at eight nucleotide positions. Both proteins encoded by DNA B (BV1 and BC1) are affected by these substitutions. Computer analysis shows that the bipartite genomes resemble those of other whitefly-transmitted geminiviruses. From homology analyses we conclude that both viruses are closely related but distinct. Comparison with a Sida-infecting virus from Costa Rica (SiGMV-Co) showed that the two viruses from Honduras are more similar to each other than either of them are to SiGMV-Co. Exchange of SiGMV-Ho and SiGMV-Ho(yv) genomic components resulted in viable pseudorecombinant viruses. SiGMV-Ho DNA A was able to produce a viable pseudorecombinant with SiGMV-Co DNA B while the reciprocal exchange was not infectious in N. benthamiana. SiGMV-Ho(yv) DNA A and SiGMV-Co DNA B produced a viable pseudorecombinant virus whereas only pseudorecombination of SiGMV-Co DNA A with SiGMV-Ho(yv) DNA B2, and not with DNA B1, was infectious in N. benthamiana.

Amino Acid Sequence↗
PubMed1997

Nucleotide sequence of a new bipartite geminivirus isolated from the common weed Sida rhombifolia in Costa Rica.

The nucleotide sequence of infectious clones of a geminivirus from Costa Rica that infects Sida rhombifolia was determined. Sida golden mosaic virus (SiGMV-Co) has a bipartite genome (DNAs A and B). Computer analysis showed that the bipartite genome of SiGMV-Co resembles that of other whitefly-transmitted geminiviruses. The DNA A (2605 nt) and DNA B (2587 nt) components have little sequence homology other than within the common region (CR). Analysis of DNAs A and B showed that SiGMV-Co is closely related to bean dwarf mosaic virus (BDMV). SiGMV-Co was introduced via agroinoculation into seven plant species, including tomato and bean.

Base Sequence↗
PubMed1997

Replantation of an inverted lower second premolar germ.

During the initial X-ray control of a 10-year-old female orthodontic patient, a late development and an inverted position of the lower left second premolar was seen. 4.3 years later the tooth with its follicle was replanted in the upright position, preserving the second deciduous molar; at that time the root development was at an early stage. At a follow-up control 4 years after the surgical procedure the replanted tooth had erupted and the sensibility response was normal. Its root, however, although completed, could not reach the length and especially the width (in the apical half) of the contralateral premolar. This relative reduction in width seems to follow a temporary thickening of that part of the root formed during the first period after replantation. The anamnestic data suggest that physiologic exfoliation of the deciduous molar took place.

Bicuspid↗
PubMed1996

Inhibition of nucleoside diphosphate kinase activity by in vitro phosphorylation by protein kinase CK2. Differential phosphorylation of NDP kinases in HeLa cells in culture.

Although a number of nucleoside diphosphate kinases (NDPKs) have been reported to act as inhibitors of metastasis or as a transcription factor in mammals, it is not known whether these functions are linked to their enzymatic activity or how this protein is regulated. In this report, we show that in vitro protein kinase CK2 catalyzed phosphorylation of human NDPK A inhibits its enzymatic activity by inhibiting the first step of its ping-pong mechanism of catalysis: its autophosphorylation. Upon in vivo 32P labeling of HeLa cells, we observed that both human NDPKs, A and B, were autophosphorylated on histidine residues, however, only the B isoform appeared to be serine phosphorylated.

Casein Kinase II↗
PubMed1996

Discrimination between acid and alkali-labile phosphorylated residues on Immobilon: phosphorylation studies of nucleoside diphosphate kinase.

We have critically analyzed current methodologies for distinguishing histidine and serine phosphorylated residues in proteins and report a simple technique that assures a reliable discrimination. Electro-transfer of a phosphorylated enzyme to Immobilon membranes and its treatment at pH 1 and 14 in buffers containing 5% methanol allows unambiguous distinction between serine/threonine and histidine phosphorylation (O-phosphomonoesters and phosphoramide, respectively) since under these conditions only one type of residue is dephosphorylated. The addition of 5% methanol to all buffers was indispensable to deplete phosphate from membranes incubated successively under acid and basic conditions. The technique was applied to the study of nucleoside diphosphate kinase (NDP kinase) phosphorylation. In this enzyme, autophosphorylation of active site histidine is an accepted intermediate step in the catalytic phosphate transfer activity of nucleoside diphosphate kinase (NDP kinase). Nonetheless, a significant degree of autophosphorylation on other residues has been reported by several laboratories, and the hypothesis has been advanced that this nonhistidine phosphorylation may play an important role in NDP kinase cellular function, signaling the suppression of metastasis in the case of human NDP kinase A. Using this improved method, we show that human, Escherichia coli and Candida albicans NDP kinases are only autophosphorylated on histidine residues. In addition, we present evidence that the presence of phosphoserine after strong acid hydrolysis of the histidine autophosphorylated enzyme is in fact a nonenzymatic transphosphorylation from phosphohistidine due to the harsh acid treatment. This methodology was also applied to in vivo phosphorylation studies of C. albicans NDP kinase. We believe that the technique will be generally useful in histidine phosphorylation screenings.

Candida albicans↗
PubMed1996

Chondroitin sulfate proteoglycans in the developing central nervous system. I. cellular sites of synthesis of neurocan and phosphacan.

We have used in situ hybridization histochemistry to examine the cellular sites of synthesis of two major nervous tissue proteoglycans, neurocan and phosphacan, in embryonic and postnatal rat brain and spinal cord. Both proteoglycans were detected only in nervous tissue. Neurocan mRNA was evident in neurons, including cerebellar granule cells and Purkinje cells, and in neurons of the hippocampal formation and cerebellar nuclei. In contrast, phosphacan message was detected only in astroglia, such as the Golgi epithelial cells of the cerebellum. At embryonic day 13-16, phosphacan mRNA is largely confined to areas of active cell proliferation (e.g., the ventricular zone of the ganglionic eminence and septal area of the brain and the ependymal layer surrounding the central canal of the spinal cord) as well as being present in the roof plate. The distribution of neurocan message is more widespread, extending to the cortex, hippocampal formation, caudate putamen, and basal telencephalic neuroepithelium, and neurocan mRNA is present in both the ependymal and mantle layers of the spinal cord but not in the roof plate. The presence of neurocan mRNA in areas where the proteoglycan is not expressed suggests that the short open reading frame in the 5'-leader of neurocan may function as a cis-acting regulatory signal for the modulation of neurocan expression in the developing central nervous system.

Animals↗
PubMed1996

Regulation of bioactive IL-12 production in lipopolysaccharide-stimulated human monocytes is determined by the expression of the p35 subunit.

IL-12 enhances IFN-gamma production by NK cells and T lymphocytes and plays a pivotal role in the development of Th1 cells. Bioactive IL-12 (p70) is composed of two subunits, p35, which is only secreted as part of the p70 dimer, and p40, which can also be secreted by itself. The IL-12 subunits are encoded by two separate genes. Therefore, we studied to what extent the expression of each of the subunits contributes to the regulation of IL-12 production. We found that in LPS-stimulated whole blood and purified monocytes, p70 and p40 production are enhanced by IFN-gamma and inhibited by IL-10 and IL-4. However, IFN-gamma and IL-10 had stronger effects on p70 production than on p40 production, and IL-4 affected p40 production more strongly. Concomitantly, in all experimental conditions tested, p40 production greatly exceeded p70 production, suggesting that p35 expression was limiting. Analysis of p35 and p40 mRNA expression by PCR confirmed this notion. Resting purified monocytes expressed neither p40 nor p35 mRNA. The effects of IFN-gamma, IL-10, and IL-4 on the p35 mRNA expression in LPS-stimulated purified monocytes were similar to the effects of these cytokines on p70 protein production, and the p40 mRNA expression corresponded to p40 protein production. Our results imply that production of the two IL-12 subunits is differently regulated for each subunit, mainly at the level of mRNA expression, and that the level of bioactive IL-12 production in monocytes in response to LPS and cytokines is determined by the level of p35 expression.

Antibodies, Monoclonal↗
PubMed1996

Risk factors and dose-effect relationship for osteoradionecrosis after hyperfractionated and conventionally fractionated radiotherapy for oral cancer.

A high frequency of osteoradionecrosis after hyperfractionated radiotherapy (RT) of head and neck tumours led to a detailed analysis of risk factors in the dental, surgical, and radiotherapeutic areas. 168 patients with oral cancer were analysed retrospectively. 19% of them had been irradiated primarily and 81% postoperatively. 116 patients received a total dose mostly ranging from 60 Gy to 70 Gy to the ICRU 29 reference point (daily single dose 2 Gy). 52 patients were treated hyperfractionally with two daily fractions of 1.2 Gy per day, 4 h minimum apart and a total dose 82.8 Gy. Dental findings could be evaluated in 126 patients. Factors were checked for prognostic significance for osteoradionecrosis (ORN). Dose dependency was computed using a PROBIT analysis. Dental status before radiotherapy was generally poor (mean 11/32 teeth present, of these 1 was dead, 2.4 carious, 2.4 loose, 0.3 destroyed). On average, six teeth (range 0-27 teeth) had to be extracted. In one-third of the patients bone surgery was necessary. ORN occurred in 8.6% of the patients treated conventionally but in 22.9% of those treated hyperfractionally (p = 0.029). Biologically effective dose (p = 0.032) and deep paradontitis (p = 0.034) proved to be significant risk factors for ORN. PROBIT analysis showed a steadily rising dose dependency of the ORN frequency after conventional radiotherapy. Using total doses up to 70 Gy the frequency of ORN was 8.6%. Dose escalation using hyperfractionation led to an intolerable ORN frequency (22.9%) where a short interfraction interval was a significant factor. The use of this dose fractionation was therefore discontinued in 1992.

Dose-Response Relationship, Radiation↗
PubMed1995

A novel serine/threonine-specific protein phosphotransferase activity of Nm23/nucleoside-diphosphate kinase.

Two human nm23 genes have been identified, designated nm23-H1 and nm23-H2, which encode the 88% identical nucleoside-diphosphate kinase (NDPK) A and NDPK B polypeptides, respectively. The nm23-H1 gene product has been shown to play a functional role in the suppression of tumor metastasis. The Nm23 proteins/NDPK are highly conserved throughout evolution and are implicated in controlling cellular differentiation and development in various species, while the underlying mechanisms remain undefined. Neither the NDPK activity nor the DNA-binding activity, identified recently for NDPK B, can satisfactory explain the regulatory functions of Nm23. The present study provides evidence that purified Nm23 proteins are capable of transferring a phosphate group to other proteins when non-denaturing amounts of urea are present. This novel Nm23/NDPK activity was found to be specific for serine and threonine residues, and the transphosphorylation of substrate proteins occurred stoichiometrically. Because of the absence of a substrate turn-over, the novel function was termed protein phosphotransferase activity instead of protein kinase activity. It is demonstrated that urea stimulates the interaction of NDPK with other proteins. Identical phosphoprotein patterns were obtained using purified NDPK preparations from human, Drosophila, yeast and Dictyostelium in the presence of urea. Partially purified NDPK from human erythrocytes produced a similar phosphorylation pattern independent of urea addition and also acted stoichiometrically. In this preparation, a protein phosphotransferase activity of Nm23 species may possibly be generated and/or stabilized by the interaction with copurified proteins. Using different mutants of Dictyostelium NDPK it was shown that the protein phosphotransferase activity depends on the same active site as the NDPK activity. A phosphotransfer mechanism analogous to that of protein-histidine kinases is proposed, involving a high-energy phosphohistidine intermediate. Furthermore, the novel Nm23 function is compared with an apparently similar protein phosphotransferase activity which was observed previously with partially purified NDPK from different plant species.

Amino Acids↗