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Biomedical subjects

H Radner

Publications and source records attributed to H Radner.

At least 55 records · Page 3Linked to original sources
PubMed1992

A new approach to the molecular basis of neoplastic transformation in the brain.

Gene transfer into living organisms has evolved as a powerful approach to study in vivo effects of specific genes and to devise animal models of hereditary disorders. We have been particularly interested in an approach to introducing transforming genes into the nervous system. Since specific promoter sequences for targeting the expression of a transgene to many cell types of the brain are not yet isolated, a suitable transgenic mouse model was not available for these experiments. This has prompted us to develop an alternative strategy for gene transfer into the brain. The rationale is to introduce foreign genes into fetal brain transplants using embryonic CNS as donor tissue and replication-defective retroviral vectors as genetic vehicles. This technique relies on the extraordinary organotypic differentiation capacity of neural grafts and the expression of retrovirally transmitted genes in different cell types of CNS transplants. In contrast to transgenic animals but analogous to sporadic tumour formation, target cells for the retroviral vector will develop in an environment of unmodified neural tissue. We have introduced a number of neurotropic oncogenes into fetal brain transplants to study potential effects of such genes on the brain. This review will summarize some of the findings which have emerged from this experimental study including the tropism of several genes for endothelial cells, attempts to identify cooperating combinations of transforming genes and an experimental model for primitive neuroectodermal tumours in neural grafts.

Animals↗
PubMed1992

Retrovirus-mediated oncogene transfer into neural transplants.

A gene transfer model was developed which allows for the identification of transformation pathways in the developing nervous system. Transforming genes were introduced into fetal brain transplants using embryonic CNS as donor tissue and replication-defective retroviral vectors as genetic vehicles. This technique relies on the extraordinary organotypic differentiation capacity of neural grafts and the expression of retrovirally transmitted genes in various cell types of CNS transplants. In contrast to transgenic animals but analogous to sporadic tumor formation, target cells for the retroviral vector develop in an environment of unmodified neural tissue. We have introduced a number of neurotropic oncogenes into fetal brain transplants including genes with an associated tyrosine kinase activity (polyoma medium T, v-src), a novel member of the fibroblast growth factor (fgf) gene family and the SV40 large T antigen. These experiments have demonstrated a significant transformation potential of oncogenes in specific target cells of the brain, provided evidence for a dominant complementary transforming effect of simultaneously expressed ras and myc genes in neural precursor cells and have yielded intriguing model systems for human CNS neoplasms such as the cerebellar medulloblastoma. This review describes the transplantation model, demonstrates several striking phenotypes induced by oncogene expression in neural grafts and elaborates on future prospects of this experimental approach.

Animals↗
PubMed1992

[The pedicled transposition of the digastric and stylohyoid muscles in the treatment of velopharyngeal incompetence. Anatomic basis and clinical application].

The anatomical basis for the application of neurovascular pedicled muscle transfers of the digastric and stylohyoid muscles in the treatment of velopharynx incompetence is described. The fact that the neurovascular pedicle is located in the cranial third of the muscle bellies provides the safety of the operative procedure. The muscles have to be dissected with respect to that. The direction in which the transferred muscles pull is described. The muscle transposition is combined with the classic Wardill-Kilner operation to lengthen the soft palate. The transferred muscles have to avoid scar contraction and shortening of the soft palate and to gain a muscular function of the soft palate. The clinical use is justified in rare cases as demonstrated in one case.

Carotid Arteries↗
PubMed1991

Pituitary hyperplasia after goserelin (LHRH-analogue) therapy.

A 78-year-old male was treated with goserelin (Zoladex) for 16 months for metastasizing prostate carcinoma. This therapy is clinically equivalent to orchidectomy, as the application of the luteinizing hormone-releasing hormone (LHRH)-analogue Zoladex causes suppression of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by down-regulation of pituitary receptors. Consequently, testicular androgen production is inhibited and testosterone levels are decreased to castration levels. In the present case we found diffuse, partially nodular hyperplasia of growth hormone (GH) and adrenocorticotropin (ACTH) producing cells in the anterior pituitary gland at autopsy. As Zoladex reduces pituitary receptors for releasing hormones (RH), a globally increased hypothalamic secretion of RH might be responsible for the ACTH- and the GH-cell hyperplasia. We cannot exclude that Zoladex may cause not only adenomas in rat pituitary glands as reported previously, but also a (nodular) hyperplasia of the pituitary gland in man.

Adrenocorticotropic Hormone↗
PubMed1990

Peculiar changes in Rosenthal fibres in an atypical astrocytoma.

A 50-year-old female patient died of an untreatable glioma apoplecticum. At autopsy a strongly vascularized glial tumour was found. The criteria for malignancy according to the WHO classification were only partially fulfilled by this tumour which displayed morphological features of an astrocytoma but could not be further subclassified. By light microscopy, angioma-like vascular proliferations, large cells with brightly eosinophilic cytoplasm, and small cells with hyperchromatic nuclei were found. Most large cells had vesicular, excentrically placed nuclei and contained fibrillary whorls or amorphous, irregular cytoplasmic inclusions. By immunohistochemical staining, using antibodies to glial fibrillary acidic protein (GFAP) the fibrillary whorls were identified as aggregates of glial filaments. The amorphous inclusions lacked GFAP immunoreactivity and appeared in the electron microscope as electron dense material surrounded by a dense network of glial filaments. The abnormal perikaryal inclusions of these atypical astrocytoma cells appeared to be peculiar alterations of Rosenthal fibres closely mimicing Mallory bodies.

Astrocytes↗
PubMed1989

The osteomusculocutaneous musculoperitoneal groin flap in head and neck reconstruction.

The anatomy of the ascending branch of the deep circumflex iliac vessels is reported. This vasculature allows the design of a musculoperitoneal flap, not exceeding 7 cm x 14 cm, together with an osteomusculocutaneous groin flap. The procedure is particularly useful, if resection of an intraoral carcinoma has included such structures as bone and the outer skin of the head and neck. The flap can be harvested with or without the internal oblique muscle. Most common composite defects after resection can be replaced by an osteomusculoperitoneal flap. Clinical applications are also described and one case report is included.

Groin↗
PubMed1989

MR findings in methotrexate-induced CNS abnormalities.

MR of the brain was performed in eight patients (mean age, 14.9 years) with osteogenic sarcoma during or after IV treatment with high-dose methotrexate. MR detected brain abnormalities in four patients, three of whom had concomitant neurologic dysfunction. Pathologic findings demonstrated on MR were (1) chronic brain edema, demonstrable over a period of 3-14 months (proved by autopsy in one patient); (2) multifocal white matter necrosis; and (3) deep brain atrophy. MR appears to be valuable in the detection of abnormalities induced by treatment with high-dose methotrexate.

Adolescent↗
PubMed1988

[Laser Doppler flowmetry in vital bone transplantation. Experimental and clinical results].

Laser Doppler Flowmetry allows the measurement of the blood flow rate of different types of tissue. Rib on a muscle pedicle was compared with rib on a vascular pedicle in an animal experiment. The morphological results were compared with the LDF-results. During eleven clinical transfers of iliac crest bone grafts and one osteocutaneous scapular flap the blood flow values were measured intraoperatively before and after the transplantation. Postoperative monitoring was possible for 48 hours with the endoscopic probe and a screw implant. The blood flow of vascularized bone transplants is excellent and even rises post-operatively in some cases.

Animals↗
PubMedDate not supplied

Temperature monitoring of interstitial thermal tissue coagulation using MR phase images.

The temperature-dependent water proton frequency shift was investigated for temperature monitoring of interstitial thermal coagulation. A procedure for on-line temperature calculation was developed, and errors due to temperature-dependent susceptibility were investigated by finite element analysis and reference measurements. The temperature coefficient of magnetic susceptibility and proton chemical shift were determined for brain tissue and other substances. With the proposed procedure, the location of isotherms could be well visualized during laser-induced interstitial coagulation in vitro and in vivo. Systematic errors caused by magnetic susceptibility changes with temperature depend strongly on the characteristics of the heat source and can exceed susceptibility effects caused by physiologic tissue changes. For the laser applicators discussed here, however, a first order compensation for this effect was found to be satisfactory, because it reduces the absolute error to the range of +/- 1 degrees C. The proposed method represents a very promising approach for monitoring of the interstitial thermal coagulation.

Adipose Tissue↗
PubMedDate not supplied

Muscle-specific overexpression of human lipoprotein lipase in mice causes increased intracellular free fatty acids and induction of peroxisomal enzymes.

A transgenic mouse model for peroxisomal and mitochondrial induction caused by increased uptake of fatty acids in muscle was established. Transgenic mouse lines were generated using a human lipoprotein lipase (LPL) mini gene (3-20 copies) driven by the promoter of the muscle creatine kinase gene. Expression of human LPL was only observed in skeletal and cardiac muscle. In proportion to the level of LPL overexpression increased LPL activity in skeletal (up to 24-fold) and cardiac (up to three-fold) muscle, decreased plasma triglyceride levels, elevated free fatty acid (FFA) uptake by muscle tissue, weight loss (due to a reduction in muscle mass as well as adipose tissue mass) and premature death were observed. A remarkable increase in the number of mitochondria and peroxisomes was detected using oxide-electron microscopy. Proliferation of mitochondria and peroxisomes was confirmed by a dose-dependent increase of marker enzyme activity (succinate-dehydrogenase and catalase). In addition, peroxisomal acyl-CoAse enzyme protein was markedly elevated whereas mRNA was increased only up to two-fold. No changes in peroxisomal proliferator activated receptor alpha mRNA was found. This degree of proliferation and enzyme activity of mitochondria and peroxisomes suggests that FFA play an important role in the induction of these organelles. In addition, myopathy characterized by excessive glycogen storage, muscle fiber degeneration, and fiber atrophy with centralization of nuclei, mimicking several forms of human myopathies was noted. Our results imply that improper regulation of muscle LPL leading to increased fatty acid levels in muscle can cause severe pathological changes. This effect may be important in the pathogenesis of human myopathies. We conclude that these transgenic mouse lines could serve as a useful animal model for the investigation of myopathies and the effects of fatty acids on the induction of mitochondria and peroxisomes.

Animals↗
PubMedDate not supplied

Lectin binding in meningiomas.

Forty-two meningiomas of different morphological sub-type were examined to determine their pattern of binding to 11 different lectins which characterize cell surface components such as carbohydrate residues. Histiocytic and xanthoma cells within meningiomas could be demonstrated with six different lectins: wheat germ agglutinin (WGA), peanut agglutinin (PNA) Bauhinia purpurea agglutinin (BPA), Helix pomatia agglutinin (HPA), Vicia fava agglutinin (VFA) and Soyabean agglutinin (SBA). Vascular elements including endothelial cells and intimal cells, bound Ulex europaeus agglutinin type 1 (UEA 1), WGA and HPA. The fibrous stroma in fibrous and fibroblastic meningiomas bound PNA, Laburnum alpinum agglutinin (LAA) and SBA. Tumour cells in meningotheliomatous meningiomas and some areas of anaplastic meningiomas bound Concanavalin A, PNA, LAA and VFA whereas tumour cells in fibrous and fibroblastic meningiomas bound BPA, LAA and VFA. Lectin binding has proved to be of value in detecting histiocytic and xanthoma cells together with vascular elements within meningiomas. In addition, the different lectin binding patterns allow different histological sub-types of meningioma to be distinguished although the biological significance of the binding patterns is unclear.

Histiocytes↗
PubMedDate not supplied

The morphologic correlate of incidental punctate white matter hyperintensities on MR images.

Postmortem examinations were made of the brains of six patients, 52-63 years old, who exhibited incidental punctate white matter hyperintensities on MR images before death. Our aim was to unravel the morphologic correlate of such lesions. By repeating the MR study after fixation on four specimens, cutting the brain parallel to the MR imaging plane, and examining whole-hemisphere microscopic sections, we optimized lesion identification. The white matter signal abnormalities were better delineated on pre- than postmortem scans, and visual inspection of the brain slices was normal in all but one location. Histologically, we found areas of reduced myelination with atrophy of the neuropil around fibrohyalinotic arteries as well as different stages of perivenous damage. The latter ranged from spongiform transformation of the neuropil and scattered foci of demyelination to large perivenous areas with marked rarefaction of myelinated fibers. Edematous glial swelling in foci of ganglion cell heterotopia caused subcortical white matter hyperintensities in one case. Our results suggest minor perivascular damage but not infarction as the most likely substrate of punctate MR white matter hyperintensities in elderly brains. Histologic correlations with MR images obtained during life or with studies of unfixed material are necessary to analyze such small lesions.

Brain↗
PubMedDate not supplied

[Immunohistochemical results obtained with bromodeoxy uridine (BUdR) labelled tumors of the head and neck].

In a prospective study 17 patients with oral PE carcinoma were given bolus injections of a non-toxic dose of BUdR, 4 hours prior to tumor surgery. BUdR replaces thymidine in the DNA of those cells which are in the S phase at the time of application. The resected tumor material was fixed in formalin and embedded in paraffin for immunohistochemical analysis using a monoclonal antibody against BUdR incorporated in DNA. The BUdR-storing cells were evaluated in 4 histologically different tumor areas. A total of 1600 cells was evaluated in each primary tumor or, in given cases, each lymph node metastasis or recurrence. In contrast to flow cytometry, this morphological method proved useful not only in comparing the number of BUdR-labelled cells with the total tumor cell population in different carcinoma segments, but also in correlating the focal proliferation tendency with the regional degree of differentiation and the number of mitotic cells even in morphologically different tissue segments. More often than not these results showed an increase in the average BUdR storage rate with increasing dedifferentiation and increasing rate of mitosis. Nevertheless, this is not the rule for each individual case. Some tumors displayed a relatively high proliferation tendency and BUdR storage rate in more highly differentiated areas (marked keratinization). Some poorly differentiated tumors or tumor areas, on the other hand, exhibited relatively low storage rates. Possibly, immunohistochemical analysis of a biopsy specimen after preoperative BUdR application may provide information on the radiosensitivity of the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Bromodeoxyuridine↗
PubMedDate not supplied

MR findings in methotrexate-induced CNS abnormalities.

MR of the brain was performed in eight patients (mean age, 14.9 years) with osteogenic sarcoma during or after IV treatment with high-dose methotrexate. MR detected brain abnormalities in four patients, three of whom had concomitant neurologic dysfunction. Pathologic findings demonstrated on MR were (1) chronic brain edema, demonstrable over a period of 3-14 months (proved by autopsy in one patient); (2) multifocal white matter necrosis; and (3) deep brain atrophy. MR appears to be valuable in the detection of abnormalities induced by treatment with high-dose methotrexate.

Adolescent↗