Biomedical subjects
Publications and source records attributed to W Roggendorf.
We report a case history of a patient whose diagnosis of AL amyloidosis remained elusive until postmortem examination. Exhaustive autonomic neuropathy mimicking a chronic Guillain-Barré syndrome dominated the clinical picture. The problems in establishing the definitive diagnosis of AL amyloidosis even in the face of strong clinical evidence are discussed.
The monoclonal antibody Ki-M1P recognizes a formalin/paraffin-resistant differentiation epitope of monocytes and their macrophage derivatives [Radzun et al., Lab Invest 65:306, 1991]. To evaluate its usefulness for neuropathology, we examined a variety of routinely processed tissues using immunohistochemistry. In normal brains, positivity was restricted to ramified microglial cells. Intense labeling of macrophages, ramified and ameboid microglial cells, and rod cells was seen in brains with various degenerative and inflammatory disorders. Astrocytes were negative as determined by double-immunofluorescence labeling using Ki-M1P and anti-glial fibrillary acidic protein (GFAP). Histiocytic lesions (histiocytosis X, xanthogranulomas, granulomatous inflammation) were immunopositive. Among 107 tumors, reactivity of Ki-M1P was observed with some schwannoma and meningioma tumor cells. In addition to macrophages, most gliomas contained small, elongated Ki-M1P-positive cells, which were negative for GFAP. Positivity was also found in two glioblastoma cell lines. Immunoblotting performed on spleen, meningioma and glioblastoma specimens revealed one to three bands in the range of 110 to 130 kDa. We conclude that Ki-M1P can serve as a reliable marker for brain macrophages and microglial cells in routinely processed normal and non-neoplastic tissues, whereas due to the unexpected immunoreactivities results obtained with neoplastic tissues should be carefully interpreted.
Three cases of periventricular neurocytomas are presented. All patients had a large but well-circumscribed, hyperdense tumor with insignificant contrast enhancement in the lateral and third ventricle, causing hydrocephalus. Calcification was present in one patient. Angiography revealed a blush tumor enhancement in two cases. Surgical removal was complete in two patients and incomplete in one. Light microscopy showed a cell pattern that resembled either ependymoma or oligodendroglioma. However, in all cases the tumor was confirmed to be a neurocytoma by immunocytochemical analysis that showed reactivity for synaptophysin and/or neuron-specific enolase in a high percentage of neoplastic cells. With respect to the literature it is concluded that neurocytomas represent an individual pathological entity of supratentorial midline tumors. Complete surgical removal without irradiation is the recommended treatment.
The clinicopathological features of two infants with desmoplastic supratentorial neuroepithelial tumours are described. The cases were similar to the 26 cases reported previously as desmoplastic infantile ganglioglioma and superficial cerebral astrocytoma attached to dura. Neuronal differentiation was absent on routine stains, but was immunohistochemically established. We review the literature and suggest classifying this clinicopathological entity by using a general designation such as desmoplastic supratentorial neuroepithelial tumours of infancy, a term which indicates the variability in the amount and lines of differentiation.
Type VIII collagen has been localized to specialized extracellular matrices in fetal tissues and has been suggested to be associated with cellular proliferation and angiogenesis (Sage and Iruela-Arispe 1990). In view of this hypothesis we studied its distribution in the normal and diseased human brain. Focal immunoreactivity was seen in histologically abnormal vessels of all 10 angiomas and 40 of 52 brain tumors. Staining was very weak in 3 embryonal and fetal brains, and it was absent in 20 normal adult brains and in 15 adult brains showing various cerebrovascular abnormalities. Our results provide additional evidence for the participation of type VIII collagen in some types of angiogenesis.
The distribution of intermediate filaments GFAP, Vimentin and Desmin was investigated in normal intracerebral and meningeal vessels in human material. Vimentin is detectable in endothelial cells of all cranial vessels. Moreover Vimentin is expressed in all vascular smooth muscle cells of the brain with the exception of arterioles in the white matter and in the pons. Desmin is only detectable in the tunica media of larger intracerebral arterioles or arteries, larger meningeal veins contain single Desmin positive smooth muscle cells. Immuno-electronmicroscopically Vimentin could be shown in endothelial and smooth muscle cells of larger venous and arteriolar vessels. We conclude from our immunohistologic investigation that there is an uneven distribution of Vimentin and Desmin in brain vessels which might reflect some ultrastructural peculiarities of brain arteries.
We present the case of a 7-year-old boy who had a solitary mass within Meckel's cave that recurred 6 weeks after the initial resection. The histological, immunohistochemical, electron-microscopical, and molecular genetical features established the lesion's histiocytic nature. Our findings showed that it was closely related to juvenile xanthogranuloma, a benign lesion that usually occurs in the skin but has not yet been histologically confirmed in the brain. The present tumor is different from other intracranial histiocytic and xanthogranulomatous lesions.
A comparative animal experiment study on rabbits was performed to test a synthetic dura (expanded polytetrafluorethylene = ePTFE = Gore-Tex Surgical Membrane). For the purpose of comparison with the ePTFE implanted in the left hemisphere, lyophilized natural dura (Lyodura) was used and removed from the subjects after two, eight and twelve weeks. There were no rejection reactions. The lyophilized dura showed pronounced environmental reaction, with cellular permeation and indications of revitalization. The ePTFE manifested only slight reaction and remained inert in an enclosing sheath of connective tissue. The biocompatibility and other properties, such as simple handling and resteriliziability, of ePTFE can thus be assessed as positive.
We report a 17-year-old boy with myelinoclastic diffuse sclerosis (Schilder's disease) presenting with left leg paresis, visual loss, and behavioral changes. CT and MRI showed two large lesions in the subcortical white matter of the occipital and parietal lobes of both hemispheres and increased intracranial pressure. Histology disclosed large areas of demyelination and perivascular infiltrates. The patient improved with coincident oral prednisolone treatment.
A 52-year-old woman noted loss of vision in August 1984. Clinical examination disclosed iris cysts and ciliary body cysts, macular edema, and uveal nevi. Cataract extraction and pressure-lowering operations were required in both eyes because of a tumor-induced angle-closure glaucoma. Vision, however, progressively decreased to light perception in each eye. Both eyes were finally enucleated because a malignant melanoma could not be ruled out, though iris tissue obtained in 1985 suggested a nevuslike process. Histologic study indicated a bilateral uveal hyperplasia. Results of light and electron microscopy, immunologic studies, and suspension cell culture suggested that the uveal hyperplasia was more likely a melanoma of low malignancy than a nevuslike process. We could not detect an extraocular primary tumor and assumed that this condition constituted an oncogenic syndrome.
Paraffin-embedded sections from paraformaldehyde-fixed rat brain were stained immunocytochemically for glycogen phosphorylase brain isozyme BB, using a monoclonal mouse antibody and the biotin-strept-avidin method, with either horseradish peroxidase or beta-galactosidase as marker enzymes. Two cell types showed strong glycogen phosphorylase-immunoreactivity: Astrocytes and ependymal cells. Most intensive staining was observed in the cerebellar cortex, the neocortex and the hippocampus. Astrocytes in the cerebellar white matter stained positively. The choroid plexus cells stained poorly or not at all. Neurons throughout the brain were negative, as well as oligodendrocytes and bundles of myelinated nerve fibers. These data are consistent with the immunocytochemical localization of glycogen phosphorylase in astroglia-rich primary cultures derived from rat brain.
Fibroblast growth factor (FGF) is a potent angiogenic factor and a mitogen for a variety of mesoderm- and neuroectoderm-derived cell types (e.g., fibroblasts, endothelial cells, astrocytes, oligodendrocytes). After application of a monospecific polyclonal antiserum, we localized basic FGF on frozen sections of 73 human brain tumors using immunohistochemistry. FGF was present in a variable number of tumor cells (16/16 astrocytomas, 5/5 ependymomas, 0/3 benign and 4/7 anaplastic oligodendrogliomas, 11/12 glioblastomas, 11/11 meningiomas, 6/6 neurilemmomas, 0/3 pituitary adenomas, 2/2 choroid plexus papillomas, 0/1 neurocytoma, 2/2 benign fibrous histiocytomas, 2/5 metastatic carcinomas). FGF was detected in vascular cells of 59 tumors and in fibroblasts of connective tissue stroma from all papillomas and metastases. These results tend to indicate FGF involvement in the malignant progression of gliomas due to an autocrine or paracrine action. Histopathological aspects of malignant gliomas (e.g., pseudopalisading or pathological vessels) could be related to FGF activity.
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Immunohistochemical analysis of inflammatory cell density and infiltrate subpopulations in 42 meningiomas was performed. Evaluation of infiltrating cell density was carried out by cell counting. Meningothelial and fibroblastic meningiomas contained an average of 3% mononuclear cells; the few lymphocytes were localized in the perivascular spaces. In subtypes with cellular atypies and recurrent tumors, the inflammatory cells increased up to 9%. We found small mononuclear cell clusters in the tumor parenchyma in addition to the perivascular infiltrates. Marked degrees of infiltration were found in anaplastic meningiomas (average 13.5% of total cells). The lymphocytic infiltrates were localized in multilayered perivascular cuffings and intraparenchymal cell clusters. The composition of the infiltrates, i.e., predominantly a mixed staining of cytotoxic/suppressor and helper cell phenotypes, did not vary in the different subtypes. We conclude: (1) that inflammatory infiltration is more frequent and denser in malignant than in benign meningiomas; and (2) that the tumor defense mechanisms in meningiomas are mediated particularly by T cell mediated immunity.
The case of a 33-year-old man with clinical features of mitochondrial encephalomyopathy is presented. He suffered from recurrent cerebral infarctions, cerebellar ataxia, deafness, retinopathy, weakness, and cardiac and renal disorders. Biochemical and light microscope investigations of skeletal muscle did not show any mitochondrial abnormality. Electron microscopy revealed the presence of a hitherto unreported peculiar "pilovacuolar" inclusion in numerous mitochondria, composed of an electron dense pile or rod within a vacuole, while globular or crystalline inclusions were absent.
An immunohistochemical method is reported using the M-II68 monoclonal antibody, which detects mitochondrial accumulations ("ragged-red fibres") in routinely processed (formalin-fixed, paraffin-embedded) muscle tissue. Ten cases with electron-microscopically and histochemically proven mitochondrial myopathy featured 4% to 24% ragged-red fibres. In a series of 50 muscle biopsies without mitochondrial myopathy, scattered ragged-red fibres (less than 0.1%) were present in a few normal and pathological muscles. The immunohistochemical method is specific for mitochondria, does not require frozen tissue and permits rapid examination of large areas.
We describe a patient with the biochemically established combination of Farber and Sandhoff disease. A 6-month-old girl of consanguineous Turkish parents presented with hoarseness, stridor, scattered skin nodules, painful swelling of hand joints and ankles, and cherry-red macular spots. Until the age of 2 years her motor and physical condition deteriorated distinctly, however her mental state remained unchanged. A biopsied skin nodule disclosed lysosomal inclusions within storage cells that were typical of Farber disease (curved tubular structures). However, other inclusions (e.g. zebra bodies) were also found. Biochemical findings included ceramide accumulation in skin nodules and cultured fibroblasts, impaired ceramide degradation on loading of cultured fibroblasts with radioactive sphingomyelin, profoundly decreased ceramidase activity in fibroblasts as well as total beta-hexosaminidase activity in fibroblasts and serum, absent hexosaminidase A and B bands on cellogel zymograms, increased urinary oligosaccharide excretion of the Sandhoff disease type, and a partial reduction of ceramidase and total beta-hexosaminidase activities in fibroblasts from her father. A diagnosis of combined Farber and Sandhoff disease was made. The effect of both enzyme deficiencies on the clinical manifestations in this patient and the genetic basis of this combination require further studies.
We describe a patient who presented shortly after birth with hyperkinetic behaviour, myoclonia, respiratory insufficiency and hepatosplenomegaly. Gaucher-like storage cells were found in bone marrow. A liver biopsy showed massive lysosomal storage morphologically different to that in known lipid storage disorders. Biochemically, the patient had partial deficiencies of beta-galactocerebrosidase, beta-glucocerebrosidase and ceramidase in skin fibroblast extracts, but the sphingomyelinase activity was normal. Glucosyl ceramide and ceramide were elevated in liver tissue. Loading of cultured fibroblasts with radioactive sphingolipid precursors indicated a profound defect in ceramide catabolism. Immunological studies in fibroblasts showed a total absence of cross-reacting material to sphingolipid activator protein 2 (SAP-2). The patient died at 16 weeks of age. The fetus from his mother's next pregnancy was similarly affected. The possibility that the disorder results from a primary defect at the level of SAP-2 is discussed. We have named this unique disorder SAP deficiency.