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U Engel

Publications and source records attributed to U Engel.

At least 19 recordsLinked to original sources

Role of endothelium and nitric oxide in histamine-induced responses in human cranial arteries and detection of mRNA encoding H1- and H2-receptors by RT-PCR.

1. Histamine induces relaxation of human cranial arteries. Studies have revealed that the relaxant histamine H1-receptor predominates in human cerebral and the H2-receptor in temporal arteries, while H1- and H2-receptors are of equal importance in the middle meningeal artery. The purpose of the present study was to examine the role of the endothelium and nitric oxide in histamine-induced responses and to show the presence of mRNA encoding H1- and H2-receptors in human cranial arteries. 2. Electrophoresis of polymerase chain reaction (PCR) products from human cerebral, middle meningeal and temporal arteries, demonstrated products corresponding to mRNA encoding both H1- and H2-receptors in arteries with and without endothelium. The amplified PCR products were sequenced and showed 100% homology with the published sequences of these histamine receptors. 3. A sensitive in vitro system was used to study vasomotor responses to histamine. In precontracted cerebral, middle meningeal and temporal arteries with and without endothelium, histamine caused a concentration-dependent relaxation with Imax values between 87% and 81% and pIC50 values between 8.14 and 7.15. In arteries without endothelium the histamine-induced relaxation was significantly less potent (Imax values between 87% and 66% and pIC50 values between 7.01 and 6.67) than in cranial arteries with an intact endothelium. 4. This addition of histamine to arteries without endothelium and pretreated with the histamine H2-antagonist, cimetidine (10(-5) M), caused a concentration-dependent contraction of the cranial arteries with Emax values between 86% and 29% and pEC50 values between 7.53 and 6.77. This contraction was blocked by the histamine H1-receptor antagonist, mepyramine (10(-7) M), and even turned into a relaxation with Imax values between 84% and 14% and pIC50 values between 7.42 and 5.86. 5. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 3 x 10(-5) M) significantly inhibited the relaxant response to histamine in cerebral and temporal arteries (pIC50 values between 7.43 and 7.13). The combined treatment with L-NAME (3 x 10(-5) M) and cimetidine (10(-5) M) caused a further displacement of the concentration-response curve (pIC50 values between 7.14 and 6.57) and decreased the maximum relaxant responses in all three cranial arteries (Imax values between 62% and 39%). 6. In conclusion, this is the first study which show mRNA encoding histamine H1- and H2-receptors in human cranial arteries. The results indicate that histamine-induced relaxation of human cranial arteries is partially mediated via an endothelial H1-receptor coupled to the production of nitric oxide and partially via a H2-receptor associated with the smooth muscle cells. In addition, there is evidence for a contractile H1-receptor in the smooth muscle cells in these arteries.

Cerebral Arteries

Comparison of the reproducibility of the WHO classifications of 1975 and 1994 of endometrial hyperplasia.

In a blinded, randomized design, six histopathologists with an interest in gynecological pathology examined the inter- and intraobserver variation of the histopathological diagnosis of endometrial hyperplasia according to the World Health Organization (WHO) classification of 1975 and the new WHO classification of 1994. On four occasions, the pathologists assessed hematoxylin/eosin-stained slides from 128 cases originally diagnosed and coded in the Snomed system as endometrial hyperplasia. In the first and third rounds, the slides were classified according to the 1975 classification and in the second and fourth rounds according to the 1994 classification. The overall interobserver agreement in the two rounds where the 1975 classification was used was 0.47 and 0.51, and the kappa values 0.24 [95% confidence interval (CI) 0.21-0.27] and 0.30 (95% CI 0.27-0.33). The overall interobserver agreement in the two rounds using the 1994 classification was 0.45 and 0.41 and the kappa values 0.25 (95% CI 0.23-0.28) and 0.20 (95% CI 0.17-0.22). Reducing the classification to two categories with clinical significance (atypical endometrial hyperplasia versus others in the 1975 classification, and atypical endometrial hyperplasia, complex versus others in the 1994 classification) increased the overall agreement of the 1975 classification in both rounds to 0.91 and of the 1994 classification to 0.92 and 0.90. The kappa values increased to 0.54 (95% CI 0.49-0.58) and 0.49 (95% CI 0.45-0.54) in the 1975 classification and to 0.59 (95% CI 0.54-0.63) and 0.42 (95% CI 0.37-0.46) in the 1994 classification. The intraobserver overall agreement for the 1975 classification ranged from 0.80 to 0.55 and the kappa values from 0.70 (95% CI 0.58-0.81) to 0.28 (95% CI 0.17-0.39). The intraobserver overall agreement for the 1994 classification ranged from 0.71 to 0.46 and the kappa values from 0.60 (95% CI 0.51-0.70) to 0.20 (95% CI 0.09-0.30). It is concluded that there is considerable inter- and intraobserver variation using both the 1975 and the 1994 classifications of endometrial hyperplasia. We propose that there is need for a specification and for a simplification of the classification.

Double-Blind Method

Lectin staining of renal tubules in normal kidney.

Lectins are glycoproteins able to bind carbohydrate structures specifically. In this study we applied six different lectins on normal renal tissue to investigate their specificity for different segments of the renal tubular system. The following lectins were used: jacalin, peanut agglutinin (PNA), wheat germ agglutinin (WGA), phytohemagglutinin E (PHA-E), concanavalin A (Con A), and Dolichos biflorus agglutinin (DBA). Particular attention was paid to jacalin lectin as its staining properties respecting the renal tubular system were not known. We showed that jacalin lectin strongly stains the luminal border of distal tubules, as well as single cells of the collecting tubules. As regards the other five lectins, PNA stained distal tubules, WGA the whole nephron, PHA-E proximal tubules, and Con A and DBA a few cells of the loop of Henle.

Humans

Decrease in Le(x) expression in esophageal adenocarcinomas arising in Barrett's epithelium.

Fifty esophageal adenocarcinomas were investigated for their expression of Le(a), Le(x), and Le(a)-Le(x). Among the 50 adenocarcinomas, 17 cases developed in Barrett's epithelium. Those 17 differed from the other 33 cases by expressing much less Le(x). Fifty-nine percent of Barrett's adenocarcinomas were Le(x) negative compared with 24% of the non-Barrett's carcinomas. All Barrett's adenocarcinomas showed less than 50% Le(x) whereas 50% of non-Barrett's carcinomas showed between 50 and 100% expression. The statistical correlation coefficient for this association was P < 0.001. Normal gastric cardia epithelium showed the same Le(x) expression in both groups. In the Barrett group, Le(x) expression decreased from normal through intestinal metaplasia and dysplasia to adenocarcinoma. This progression was not seen in the non-Barrett group. Loss of Le(x) expression may prove useful in following patients with Barrett's epithelium in evaluating progression toward a malignant process. No difference in expression of Le(a) and Le(a)-Le(x) was found between Barrett's and non-Barrett's carcinomas.

Adenocarcinoma

Oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells derived from adult rat spinal cord: in vitro characteristics and response to PDGF, bFGF and NT-3.

We have analysed in detail the properties of oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells derived from the spinal cords of adult rats to gain further insights into the mechanisms that control the generation of oligodendrocytes in the healthy and demyelinated adult central nervous systems (CNS). When O-2A progenitor cells from adult spinal cord are exposed in vitro to the AA homodimeric form of platelet-derived growth factor (PDGF-AA), they express a unipolar morphology, an O4-positive, vimentin-negative antigenic phenotype, divide at slow rates, and appear to generate oligodendrocytes by asymmetric division and differentiation. Furthermore, exposure of these cells to PDGF-AA is sufficient to stimulate their proliferation at clonal density. When adult spinal cord O-2A progenitor cells are exposed simultaneously to PDGF-AA and basic fibroblast growth factor (PDGF/bFGF), they are almost completely inhibited from differentiating into oligodendrocytes, divide more rapidly than cells treated with PDGF-AA, and express a bipolar morphology and an O4-negative, vimentin-positive antigenic phenotype. These findings indicate that adult spinal cord O-2A progenitor cells resemble in many aspects their well-characterised adult optic nerve counterparts. In addition, evidence is presented to indicate that neurotrophin-3 (NT-3) is not mitogenic for adult spinal cord O-2A progenitor cells and that it does not enhance their proliferative response to PDGF-AA or PDGF/bFGF. Since relatively large numbers of O-2A progenitor cells can be obtained from adult spinal cord, it should facilitate the further characterisation of these cells.

Animals

Lectin staining of renal cell tumours with special emphasis on oncocytomas.

There are conflicting results respecting the segmental tubular origin of renal oncocytomas, a type of tumour said to be highly differentiated and benign, though metastases have been described. The aim of this study was, by applying different lectins on renal cell carcinomas (n = 50) and oncocytomas (n = 12), to search for patterns which could indicate a specific segmental origin of oncocytomas and perhaps elucidate the differentiation of this tumour. The following lectins were applied: jacalin, peanut agglutinin (PNA), wheat germ agglutinin (WGA), phytohemagglutinin E (PHA-E), concanavalin A (Con A), and Dolichos biflorus agglutinin (DBA). The results show that oncocytomas are positive when jacalin, a Lectin that stains distal tubules and collecting tubules, is used, supporting the view that the tumour derives from distal or collecting tubules. The staining of the oncocytomas is generally polarized as in normal kidney tubules underlining that the tumour is highly differentiated. Two oncocytomas with aggressive behaviour showed areas with a diffuse pattern suggesting lower differentiation.

Adenoma, Oxyphilic

From rodent glial precursor cell to human glial neoplasia in the oligodendrocyte-type-2 astrocyte lineage.

With only a few exceptions, the precursor cells representing the normal counterparts of human tumours are unknown. The comparative lack of information about the lineages involved in tissue development, and difficulties in growing many human tumors in a manner suitable for cellular biological analysis, together often make it difficult to study the differences between normal and tumor cells and to develop many of the model systems that would be useful in the study of human cancer. By applying techniques previously utilized to study glial progenitor cells, we have isolated a human glioblastoma multiforme (GBM)-derived population that expresses many properties otherwise uniquely expressed by oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. Hu-O-2A/Gb1 (for Human O-2A lineage Glioblastoma number 1) cells responded to similar mitogens and differentiation modulators as rodent O-2A progenitors, and generated cells with features of precursor cells, oligodendrocytes and astrocytes. Moreover, 1H-NMR analysis of amino acid composition demonstrated a striking conversation of types and quantities of free amino acids between the human tumour cells and the rodent primary cells. Hu-O-2A/Gb1 cells represent the first human glioma-derived population for which unambiguous lineage assignment has been possible, and our results indicate that the human O-2A lineage can contribute to one of the most malignant of glial tumours. In addition, the highly diagnostic 1H-NMR spectrum expressed by Hu-O-2A/Gb1 cells raises the possibility of eventual non-invasive identification of tumors of this lineage.

Animals

Renal cell carcinoma: prognostic factors.

OBJECTIVE: To establish the prognostic value of a series of pre-operative, per-operative and histopathological parameters in relation to renal cell carcinoma (RCC). PATIENTS AND METHODS: This retrospective study involved a consecutive series of 76 patients (46 men and 30 women with a mean age of 65.3 years [range 44-91]) with a histologically confirmed diagnosis of RCC. Patients who were admitted over the period 1980-1984 were included. Data such as erythrocyte sedimentation rate (ESR), alkaline phosphatase level, histological tumour grade, degree of necrosis and presence of tumour vessels were evaluated in relation to actuarial survival. RESULTS: The ESR and alkaline phosphatase level at the time of diagnosis of RCC, the histological tumour grade, degree of necrosis and presence of tumour vessels on angiography were all found to affect the actuarial length of survival significantly (P < or = 0.05 log-rank test). Macroscopic tumour demarcation estimated per-operatively by the surgeon or after surgery by the pathologist, microscopic demarcation, vascular density on histological examination, tumour diameter and vascular density on angiography were found not to affect actuarial survival significantly. CONCLUSION: The value of establishing simple and reliable diagnostic indicators for patients with RCC is stressed.

Adult

Nucleolar organizer regions (AgNORs) in primary and recurrent gliomas. A retrospective study.

To assess the diagnostic and prognostic relevance of nucleolar organizer regions (AgNORs) the silver-stained AgNOR structures of 46 human gliomas (22 primary gliomas, 21 first and 3 second recurrences) from 28 patients were counted and measured. Surgical specimens of two neuropathological centres were included in this retrospective study. The tumours were classified into 8 groups according to WHO criteria of diagnosis and grading and their state of recurrence: 1: primary glioma grade II; 2: primary glioma grade III; 3: glioblastoma grade IV; 4: first recurrence of glioma grade II; 5: first recurrence of glioma grade III; 6: first recurrence of glioblastoma grade IV; 7: second recurrence of glioma grade II and 8: second recurrence of glioma grade III. AgNOR numbers demonstrated a positive correlation with increasing histological grade. Similarly, higher levels of AgNORs were in general found in recurrent tumours compared to primary tumours with few exceptions in groups, in which few numbers only could be analyzed. The present study demonstrates the utility of evaluating AgNOR in assessing malignant gliomas and indicates that recurrences have a higher proliferative potential than original tumours. The problems of standardization of the AgNOR technique are especially crucial for the retrospective evaluation of fixed and embedded pathological material.

Adult

[Menkes' kinky hair disease: a clinical and pathological case report with special reference to glial changes in the brain damage].

Menkes' kinky hair disease (Kinky hair disease, trichopoliodystrophy) is a rare hereditary disease of copper metabolism. In this study we report about the case of a boy with a long course of disease who died at the age of 6. The last phase of the disease was characterized by an almost uncontrollable excitation stage and later by an apallic syndrome. Clinical course and autopsy result are presented here. The protracted course obviously led to unusual neuropathological changes. In addition to the known neuronal damages an excessive reactive gliosis could be found. The unusual neuropathological course of this gliosis perhaps allows the conclusion that apart from neuronal damages disturbances of copper metabolism have an influence on the glia.

Brain

[Limited radical approach in differentiated thyroid gland cancers. A prospective study of 107 patients].

From 1979 until 1987 a prospective study about limited radical therapy of 107 patients with differentiated cancer of the thyroid was performed. Nearly all of the tumors were occult papillary or encapsulated papillary and follicular carcinomas. The thyroid was not completely resected. Postoperative therapy consisted in TSH-suppression. After a follow-up of 7.5 (5-12) years one patient had died because of the tumor disease. Four patients had to be reoperated for lymph node metastases and then stayed free of disease as all other patients.

Adenocarcinoma, Follicular

Safety effects of speed reducing measures in Danish residential areas.

On May 1, 1977 a new code was introduced into the Danish Road Traffic Act. The result was a change in layout and speed limits in a great number of residential streets; in most cases the streets were transformed into 30 km/h streets and in few cases into 15 km/h streets. In addition to speed signs, both types of streets were equipped with speed reducing measures. Based on experiences from a selection of experimental streets, mostly 30 km/h streets, different, but very positive effects were found. Overall there was a reduction in the mean speed in these areas of 11 km/h. On the 223 km, 30 km/h streets there was a reduction of 77 accidents and 88 casualties within a period of three years. These reductions were caused by the implementation of speed signs, speed reducing measures, and a reduction in traffic. On the basis of 44 experimental streets, where traffic was recorded both before and after the changes, the reduction in risk of casualties, i.e. the number of casualties per road user km, was 72%, while the risk of accidents seemed to be unchanged. Considering serious injuries alone, a very high reduction of 78% was found. Accidents included in the study consist of all police reported accidents, i.e. accidents with personal injury as well as damage only accidents.

Accidents, Traffic

Myocardial perfusion at fatal infarction: location and size of scintigraphic defects.

In a consecutive study of myocardial scintigraphy in acute ischemic syndrome, four patients had 99mTc-hexamibi injected intravenously before they developed fatal cardiogenic shock. Planar scintigraphy was performed after death. Slices of the hearts after autopsy were analyzed for scintigraphic and pathoanatomic abnormalities. Location of perfusion defects in planar views of the heart was in good agreement with the scintigraphied, sliced sections. The extent of infarction judged from inspection and formasan staining was much smaller (7%-40% and 6%-43% of the total slice area) than found at scintigraphy, where 83%-92% of the myocardium showed ischemia as defined by a 99mTc-hexamibi uptake below an arbitrary limit on half maximum uptake. Myocardial hypoperfusion might thus aggravate the functional impairment at myocardial infarction and lead to cardiogenic shock.

Aged

[The morphology of hemostasis failure in gliosal brain tumors].

A retrospective study was conducted into 37 brains of patients, who had died of Grade 2-4 glioma. For assessment of morphological signs of hemorheological failure, microcirculation was checked by H & E, Klüver-Barrera, and Goldner staining as well as by staining for fibrin, using a modified technique according to Zerbino and Lukasewitsh. Microthrombosis was recorded from 30 in the above 37 brains, all of them related to patients with Grade 3 glioma and glioblastoma. Fibrin thrombi represented the predominant variant of microthrombosis. They exhibited differentiated characteristics depending on their localisation in the central and the peripheral regions of the tumour or in surrounding brain tissue. Also included in the study were rates of vascular proliferation and types of necrosis as well as relations between these and microthrombi. The role played by microthrombi in such cases of glial tumours is discussed in some detail.

Adult

[Aneurysm at the base of the brain and tuberous sclerosis].

Reported is the rare case of intracranial aneurysm in a boy aged one year with tuberous sclerosis. Inconspicuous development in the first few months after birth was followed, in the sixth month of age, by aggravating manifestation of convulsive seizures which were clinically diagnosed as tuberous sclerosis. Rapid progression of the clinical pattern was preterminally followed by cerebral haemorrhage which was caused by circumscribed, partially purulent arteritis along with formation of a mycotic aneurysm on the anterior segments of the arterial circle of Willis. The development of this aneurysm is discussed in conjunction with the morphological and clinical findings of tuberous sclerosis.

Aneurysm, Infected

Eosinophilic renal cell tumours. A study on tumour heterogeneity with special emphasis on oncocytes.

Eosinophilic renal tumour cells are found in oncocytomas, granular cell carcinomas, clear cell carcinomas and in a recently defined entity known as "congeners of oncocytomas". Ultrastructural examination of paraffin embedded tumour tissue representing eosinophilic areas in 40 renal cell tumours was performed in order to characterize the different types of eosinophilic cells. The results showed all tumours diagnosed light microscopically as oncocytomas to be composed of cells containing abundant mitochondria. Similar cells were, however, also found in one case of a clear cell carcinoma and in one case diagnosed light microscopically as a "congener". Oncocytes may therefore be found as part of non-oncocytomas and there seems to be a gradual transition from oncocytes to other eosinophilic cells of renal cell carcinomas. Preoperative subclassification of renal cell tumours based on small biopsy specimens is thus of limited value.

Adenoma

[Diffuse primary leptomeningeal gliomatosis].

A woman died at the age of 22 years. Lifetime diagnosis had been inflammatory arachnopathy. The course of the disease had taken at least 6 years. Autopsy revealed primary diffuse leptomeningeal astrocytoma of the brain and spinal cord without neoplastic foci in the parenchyma of the central nervous system. Patchy dystrophic calcifications were recorded from the cerebral and cerebellar cortex.

Adult