Biomedical subjects

R Laas

Publications and source records attributed to R Laas.

At least 19 recordsLinked to original sources

PubMed2001

[Immunohistochemical detection of hormones in hypophyseal adenomas of the rat after fractionated irradiation].

BACKGROUND: The aim of this study was to determine the hormones produced in pituitary gland tumours (TM) following fractionated external irradiation in rats. The TM arose in the course of studies on other questions of radiation effects. METHODS: The left neck and skull base of sixty female Wistar rats, 3 to 4 months of age at the beginning of the external irradiation, were subjected to roentgen rays exposure, fractionated to 2 Grays daily, either up to 20, 40 or 60 Gy. The midline of the neck and skull was always inside the radiation field. The animals were sacrificed either 6 months or 12 months after completion of the randomly assigned irradiation protocol. Five non-irradiated rats served as controls. RESULTS: No TM developed in the non-irradiated animals. Out of 60 irradiated rats 9 developed a pituitary TM (15%). In remnants of the normal adenohypophysis we revealed immunohistochemical reactivity for growth hormone (GH), adrenocorticotropic hormone (ACTH), prolactin (PRL), thyroid stimulating hormone (TSH), and follicle stimulating hormone (FSH). In the radiation-induced adenomas, 4 TM were immuno-reactive for TSH, 4 for GH, 2 for PRL, and 2 for FSH. The TM did not react with anti-ACTH and anti-LH (luteinizing hormone) anti-sera. CONCLUSIONS: Obviously, irradiation accelerates the development of pituitary gland adenomas. In this series the TM were predominantly incidental findings at necropsies after pretermed follow-up intervals with a variety of hormone-producing cells. On the other hand, four of nine TM were null adenomas. Necropsies of the brain should be carried out routinely in irradiation studies of the skull.

Adenoma↗

PubMed2000

Common variable immunodeficiency (CVID) and inclusion body myositis (IBM).

A case of a 38-year old man with a common variable immunodeficiency syndrome (CVID) is demonstrated who suffered at the same time from a histologically proven inclusion body myositis (IBM). The myositis did not resolve after institution of regular intravenous IgG infusions. This case demonstrates a very long lasting benign course of IBM. The occurrence with CVID may be a clinical hint for a viral pathogenesis of IBM. So far only two similar cases are reported in the literature.

Adult↗

PubMed1999

Allelic losses at 1p, 9q, 10q, 14q, and 22q in the progression of aggressive meningiomas and undifferentiated meningeal sarcomas.

Meningiomas are usually benign tumors; however, they can recur after surgical resection and occasionally show histological progression to a higher malignancy grade. Five such rare cases of aggressively recurring meningiomas were present in our departmental cohort of 923 primary meningeal neoplasms operated over a 17-year period. Four other aggressively recurring meningeal tumors with a very similar clinical and histomorphological appearance (three undifferentiated meningeal sarcomas, one hemangiopericytoma) was also included in this study. We investigated whether disease progression can be traced by genetic alterations and whether a pattern of genetic alterations is specific for meningiomas. A total of 40 specimens from primary tumors and multiple recurrences of the nine patients were analyzed with 26 polymorphic allelic markers for deletions on 1p, 1q, 9q, 10q, 14q, and 22q. Loss of heterozygosity (LOH) at 22q was observed in all meningiomas cases at the earliest time point analyzed. Allelic loss at 1p was seen in the original tumor in two cases and upon meningioma recurrence in two others. Deletion on 10q occurred during tumor progression in two cases, and on 9q and 14q in one case. While allelic loss at 22q appears to be an early event in aggressive meningioma disease, there is a clear correlation of further deletions on chromosome arms 1p, 9q, 10q, and 14q with histopathological and clinical progression, as shown in these intraindividual trackings. None of these genetic findings were present in the non-meningiomatous meningeal tumors, indicating that meningothelial cells have their own lineage-specific genetic pathways towards clinical malignancy.

Adult↗

PubMed1999

Prognostic relevance of TP53 mutations, p53 protein, Ki-67 index and conventional histological grading in oligodendrogliomas.

The prognostic value of tumour grading according to WHO, Ki-67 proliferation index, p53 labelling index and TP53 gene mutations was assessed in 59 patients (33 oligodendrogliomas WHO grade II, 15 anaplastic oligodendrogliomas, 11 glioblastomas with oligodendroglial growth pattern). The minimal observation period was 5 years after operation. According to multivariate correlation and regression tree (CART) analysis grading was the prime prognostic factor (grade II vs. anaplastic tumours, p < 0.00001). Grade II oligodendrogliomas were further divided into tumours with and without TP53 mutations (p < 0.05) whereas anaplastic tumours were subdivided according to age (p < 0.05, cut off at 57 years) and p53 protein accumulation (p < 0.05, cut off at 2%, age 57 years). Ki-67 labelling index correlated highly significantly with grading but had no independent prognostic relevance in CART analysis. Accumulation of wild-type p53 protein was not related to bcl-2 expression, a co-expression of p53 and bcl-2 was found at similar frequencies in tumours with or without TP53 mutations (4/12 vs. 3/11). Since accumulation of wild-type and mutant p53 are both associated with a poor prognosis, it is suggested to include immunohistochemical evaluation of p53 protein in routine diagnostics of oligodendrogliomas.

Adult↗

PubMed1998

Increased proliferative activity due to necroses induced by pre-operative embolization in benign meningiomas.

The proliferative behaviour of 35 benign intracranial meningiomas was investigated which were embolized for devascularization 3 to 268 hours prior to surgical exstirpation. The nuclear proliferation antigen Ki-67 was visualized by means of the monoclonal antibody MIB1 on formalin fixed and paraffin embedded tissue. Tumor cells and inflammatory reactions were recognized by means of conventional staining procedures and by immunohistochemical detection of HAM56, LCA, HLA-DR, CD15-epitope and vimentin. Extravasation and proliferation of granulocytes, macrophages, lymphocytes and the degree of expression of MHCII antigens was estimated according to a 7-point ordinal scale. Confirming preliminary observations of others the proliferation index within the perinecrotic tumor rim (PIperinec) exceeded that of intact tissue highly significantly. PIperinec peaked at the third to fourth day after embolization and kept this level until the seventh day. The time course of PIperinec was paralleled by that of macrophages, whereas--expectedly--granulocytes occured earlier and lymphocytes and HLA-DR-positivity somewhat later. The timely relationships suggested that the perinecrotic increase in tumor cell proliferation was mainly due to macrophage-born mitogens. Perinecrotic proliferative activity in embolized meningiomas does not reflect genuine tumor proliferation and should not be used for assessment of the presence or degree of malignancy in a given tumor.

Adult↗

PubMed1996

Demonstration of p53 protein and TP53 gene mutations in oligodendrogliomas.

Paraffin embedded tissue of 84 oligodendrogliomas (63 primary tumours, 21 recurrences), 21 glioblastomas with oligodendroglial growth pattern (15 primaries, 6 recurrences) and 17 mixed gliomas was investigated for the presence of mutations in exons 5-9 by means of single stranded conformation polymorphism (SCCP), temperature gradient gel electrophoresis (TGGE) and direct DNA sequencing. In parallel, p53 protein accumulation was determined by means of immunohistochemistry. The percentage of mutations was found to be higher than previously reported (6 of 44 grade II oligodendrogliomas, 4 of 19 grade III oligodendrogliomas, 4 of 15 glioblastomas). In 4 cases, the mutations lead to distinct changes in the primary or secondary structure of the protein (cysteine-->tyrosine, proline-->leucine) and were associated with marked accumulation of p53 protein. A significant correlation between p53 protein accumulation and TP53 gene aberrations was found (P < 0.001), although p53 protein accumulation was detected more often than TP53 gene anomalies, indicating that factors other than TP53 gene mutation may also lead to a p53 protein accumulation in the tumour cells. A significant correlation was found for p53 protein accumulation and tumour grade but not TP53 gene mutations. In conclusion, evaluation of p53 protein accumulation reflected the clinical course of oligodendrogliomas better than the mere presence of TP53 gene mutations.

Adult↗

PubMed1994

The direct carotid cavernous fistula: a clinical, pathoanatomical, and physical study.

In order to further elucidate the pathogenesis of the direct carotid cavernous fistulas (dCCF) clinical, patho-anatomical, and physico-mechanical studies were performed. In 27 of 42 patients the dCCF were found to be localized in the segment C4 (according to Teufel, 12), in 13 patients in segment C2 and in only 2 patients in segment C3. The patients with dCCF in segment C4 were significantly younger than those with dCCF in the segments C2 or C3. In none of the patients fractures of the bony walls of the cavernous part of the internal carotid artery (ICA) could be ascertained. On human cadavers it was affirmed that the cavernous branches of the ICA arise nearly exclusively from the top of segment C3 and from the lateral wall of segment C2. The strength of the wall of the cavernous part of the ICA was shown to decline with age as revealed by means of a tensile machine. There were no significant differences between the four segments investigated. As revealed by roentgenograms the distensibility of the ICA within its coverings was shown to be greatest in the segments C2 and C4 and lowest in segment C3. A sudden increase of the intraluminal pressure ruptured the ICA exclusively in the segments C2 and C4. Histological preparations revealed that the trabeculae of the cavernous sinus insert tangentially into the adventitia of the ICA. Taken together these findings strongly support the view that the dCCF are mainly due to a sudden increase of the intraluminal pressure of the ICA.

Adult↗

PubMed1994

Hirano bodies and chronic alcoholism.

Experiments on rodents have shown convincingly that chronic ethanol ingestion may damage the hippocampal formation. Nevertheless this region has, hitherto, not been considered as a target for alcoholism-induced brain lesions in man. Guided by the observation of increased numbers of Hirano bodies (HB) in the hippocampus of chronic alcoholics, this study determines the maximum number of HB per high power field (HPF: 0.19 mm2) in the stratum pyramidale (HBpyr) and in the stratum lacunosum (HBlac) of Ammon's horn in 123 chronic alcoholics and in 197 controls. The average count of HBlac found in alcoholics was 14.4 (SD = 17.7) compared with 4.2 (SD = 7.4) in non-alcoholics (P < 0.001). Counts of more than 19 HBlac per HPF were revealed as highly indicative of chronic alcoholism being observed in 33 (27%) alcoholics and in six (3%) non-alcoholics (P < 0.001). An increased number of HBlac was the most frequent of the neuropathological findings in the alcoholics. Affirming observations of others, the count of HBlac peaked during middle age and declined thereafter. The maximum count of HBpyr, in contrast, increased with age and was independent of alcoholism. It is proposed that increased numbers of HBlac indicate alterations of the apical dendrites of the pyramidal neurons of the CA1 field of Ammon's horn which probably are due to direct neurotoxic effects of ethanol and which may be reversible in nature.

Adult↗

PubMed1992

The carbohydrate epitope 3-fucosyl-N-acetyllactosamine is developmentally regulated in the human cerebellum.

The carbohydrate epitope 3-fucosyl-N-acetyl-lactosamine (CD15) is involved, as a constituent of glycoconjugates, in cell-cell interactions and cell sorting during rodent CNS morphogenesis. The present study was designed to test whether CD15 is also involved in the development of the human CNS. Human cerebellar hemispheres and vermes from the 24th week of gestation (wg) to the 26th postnatal month (pnm) and from adults were investigated for CD15 immunoreactivity, using the monoclonal antibody MMA. Our findings establish that the carbohydrate moiety is developmentally regulated in neuronal and glial cells during their differentiation. First, the parallel fibers of granule cells are CD15+ during the epoch of synaptogenesis with Purkinje cell dendrites. Second, a subpopulation of neurons from the dentate nucleus is transiently CD15+ from the 32nd wg until the 15th pnm. Third, at the onset of myelination (around the 35th wg), CD15 immunoreactivity is discernible in the cytoplasm of young oligodendrocytes. Immunoreactivity on protoplasmic astrocytes of the inner granular layer and on fibrous astrocytes of the white matter progressively increases during fetal development. In addition, the CD15 epitope is persistently present on Bergmann glial processes and ependymal cells. Within the three subdivisions of the cerebellum, i.e., hemispheres, vermis, and flocculonodular lobe, the CD15 expression follows a different timing of morphogenesis. For example, diminution of immunoreactivity in the parallel fibers occurs first in the phylogenetically older flocculonodular lobe and vermis, and later in the phylogenetically younger hemispheres. This study shows that in the human cerebellum the distribution of CD15 undergoes marked developmental changes. This epitope may also act in cell-to-cell recognition, and perhaps could play a role in controlling CNS development.

Adult↗

PubMed1992

Haemorrhagic thiamine deficient encephalopathy following prolonged parenteral nutrition.

Neuropathological examination of three patients who were maintained on parenteral nutrition without substitution of thiamine demonstrated an acute haemorrhagic encephalopathy. The lesions differed substantially from the classic features of thiamine deficient encephalopathy regarding the histopathological alterations and the topographical distribution. The extreme rapidity of thiamine deprivation may have been responsible for the abrupt clinical onset of the disease and the intensity of the morphological alterations.

Adult↗

PubMed1992

Microgastria-hypoplastic upper limb association: a severe expression including microphthalmia, single nostril and arhinencephaly.

Report on a female infant with iris coloboma on the right and microphthalmia/orbital cyst on the left, single nostril, radial defectis, abnormal lung lobation, congenital heart defect, hypoplastic spleen, absent gallbladder, microgastria, unilateral renal aplasia, arhinencephaly and fused thalami. This case represents an unusually severe expression of a probably rare association recently reviewed by Lueder et al. (1989).

Abnormalities, Multiple↗

PubMed1990

Agnathia, holoprosencephaly, and situs inversus: a third report.

We report on a male infant with cyclopia, agnathia, and situs inversus. In addition, anal atresia and horseshoe-kidneys were present. To our knowledge, this is the third published case of the "agnathia-holoprosencephaly-further midline defects association."

Abnormalities, Multiple↗

PubMed1988

Biological and karyotypic characterization of a new cell line derived from human gliosarcoma.

A cell line (NCE-G28) was established from the biopsy material of a human gliosarcoma of low histological differentiation. The initial cultures showed a mixed population of cells which in later stages became more uniform due to loss of slower growing constituents. The cells have been growing steadily for 20 months. A suspension of NCE-G28 cells injected s.c. as well as i.p. into nude mice produced solid tumors in all cases. Histologically these tumors closely resembled the original tumor. The original tumor, the nude mouse tumor, and NCE-G28 cells were immunochemically positive for glial fibrillary acidic protein as well as for neural plasma membrane antigen A2B5 expression. Two cell strains, 9B2C and 9B2E, were obtained by cloning of the initial cultures and another strain, NCE-G28T, was derived after explantation of a mouse heterotransplant. The two subclones were negative for glial fibrillary acidic protein expression but stained for cell surface fibronectin. NCE-G28T cells initially were positive for glial fibrillary acidic protein but lost this property within 8 months of cultivation. Karyotype analysis of NCE-G28 and the three strains revealed hyperdiploidy and six structurally altered marker chromosomes five of which were shared by nearly all cells. Receptors for epidermal growth factor were detected in all cell lines with the highest levels (about 300,000 receptors/cell) in the parental cell line. The epidermal growth factor receptors had an affinity of 2.5 nM (Kd) and by affinity cross-linking analysis a molecular weight of 170,000 was found. Initially, NCE-G28 cells responded to epidermal growth factor as well as fibroblast growth factor with increased rates of proliferation, while platelet derived growth factor had no effect. In higher passages the growth factor sensitivity was reduced. Using antibodies directed against synthetic protooncogene peptides the production of c-sis immunoreactive material was detected. NCE-G28 cells produce an autocrine factor which stimulated proliferation. This factor is present in conditioned medium and is active on cultured meningiomas and other glioma cell lines. NCE-G28 cells can be maintained in serum-free defined medium on plastic coated with fibronectin or an extracellular matrix from bovine corneal endothelial cells. The NCE-G28 cell line with its strains provide an in vitro model system in which the complexity of gliosarcoma cell populations and the interaction of the cloned cellular constituents can be studied.

Aged↗

PubMed1987

Cerebellar haemorrhage as a complication after supratentorial craniotomy.

Four cases are presented, in whom cerebellar haemorrhages appeared as a complication following supratentorial craniotomy for a giant aneurysm, for tumours in three cases. Two patients died. Intracranial hypotension in combination with disturbed blood coagulation is discussed as possible pathogenesis. Because this seems to be a rare complication--similar cases have not yet been described in the literature--its timely diagnosis may be missed.

Adult↗

PubMed1987

Three cases of intramedullary spinal hemangioblastoma: the role of intraoperative histological diagnosis.

Three cases of intramedullary spinal hemangioblastoma are presented. Since the tissue adjacent to the neoplasm often shows a gliosis resembling an astrocytoma, a misinterpretation in the intraoperative histological diagnosis may lead to an unnecessary extirpation of the reactive tissue. It is recommended that biopsies be performed in cases in which a hemangioblastoma being considered. This is necessary in order to get specimen from the hemangioblastoma itself for the intraoperative histological evaluation.

Adult↗

PubMed1986

Duration versus degree of hypotension as critical conditions of brain infarction in the albino rat.

In 41 anesthetized, spontaneously breathing male adult albino rats, cerebral hypotension of precisely defined duration and magnitude was induced by means of controlled arterial hemorrhage. One common carotid artery was occluded throughout the hypotensive period, and the target pressure was monitored in the ipsilateral internal carotid artery. Regional brain infarcts developed in all 16 animals with a target pressure of 14 mm Hg maintained for 90 minutes and in all five animals with a target pressure of 12 mm Hg maintained for 70 minutes. However, the brains of all 10 rats with a target pressure of 17 mm Hg maintained for 80 minutes remained intact. In two further groups of five animals each with target pressures of 15 mm Hg for 80 minutes and 16 mm Hg for 90 minutes the incidence of infarct was about 30%. There were no marked differences between the five groups of rats in body weight, body temperature, heart rate, respiratory rate, PaO2, PaCO2, arterial pH, or hematocrit. The data suggest that, in the rat, the clear-cut threshold for the induction of brain infarcts is a function of the severity and duration of arterial hypotension. Evidence is presented indicating that this function is distinctly species-dependent, due to species differences in the dilatory capacity of the arteries supplying the brain rather than species differences in brain vulnerability.

Animals↗

PubMed1985

Subcellular distribution of glutamic acid decarboxylase in rat brain regions following electroconvulsive stimulation.

Electroconvulsive stimulation of rats evoked significant increases of glutamic acid decarboxylase (GAD) activity in the synaptosomal fractions of neocortex (including white matter) and hippocampal formation. The elevation of synaptosomal-bound GAD activity was not significant in cingulate cortex, striatum, caudal brainstem and thalamus. The electroconvulsive shocks had no effect on the GAD activity of the cytoplasmic fractions of any brain regions investigated. The highest physiological level of synaptosomal GAD activity was found in thalamus, followed (in decreasing order) by striatum, hippocampus, cingulate cortex, caudal brainstem and neocortex.

Animals↗

PubMed1984

CCT and sonographic findings in congenital craniopharyngioma.

In a case of congenital craniopharyngioma results of the sonographic and CCT examinations are reported and compared with postmortem macroscopic cuts. Comparison is made of clinical data from six cases with congenital craniopharyngioma as reported in the literature.

Craniopharyngioma↗