Biomedical subjects
Publications and source records attributed to A Probst.
Some aspects of quantitative assessment of senile and vascular changes in brains of old, demented people are discussed. Particular emphasis is placed upon neuritic plaque count and upon the amount of softened brain parenchyma relative to the degree of intellectual deterioration. The functional significance of the topography of ischemic lesions is stressed in some cases.
A cerebellar ganglioglioma was surgically removed from a two-year old boy, who had developed manifestations of increased intracranial pressure and cerebellar symptoms. At surgery, the tumor presented as a firm nodular mass displacing the cerebellar cortex. By light microscopy, its architecture differed distinctly from that of hamartomatous diffuse hypertrophy of the cerebellar cortex (Lhermitte-Duclos' disease). Mature ganglion cells were grouped in clusters and linked by thick bundles of nerve cell processes. Nerve cells and processes were enmeshed in a rich network of fibrillary connective tissue. Electron microscopy disclosed typical neuronal perikarya as well as numerous asymmetric chemical synapses. The bulk of the tumor consisted of tightly grouped, (non-myelinated) nerve cell processes arranged in parallel. One of the most prominent features of the tumor consisted of numerous dilatations of these processes. The largest ones contained microfilaments, while the smaller ones were entirely filled with dense bodies (most probably derived from degenerating mitochondria). Only scattered dense core vesicles were seen, which probably did not represent neurosecretory granules. A second cell type consisted probably of astrocytes. Most neuroepithelial cell processes could not be identified with certainty as being of either neuronal or glial origin. A third cell type consisted of numerous slender cells which were probably mesenchymal. They were surrounded by a network of basement membrane which extended between the surrounding nerve cell processes.
A patient presenting with von Hippel-Lindau's disease, syringomyelia, bilateral pheochromocytoma and a multihormonal pancreatic tumor is described. We suggest that this syndrome results from a complex neuroendocrine disorder.
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A sporadic case of tuberous sclerosis in a stillborn infant is reported. The death at the 31st week of gestation was presumably due to the development of enormous rhabdomyomas of the heart. The typical cerebral lesions were fully developed as in patients decreased later in life. The atypical cells found in the cortical tubers demonstrated ultractructural features of reactive astrocytes. Moreover, they showed innumerable microvillilike projections on their surface and junctional complexes, mostly of the zonula adharens type, reminescent of ependymocytes. The significance of such glio-epithelial cellular features is discussed.
Morphological findings of 3 cases of Kaeser's scapulo-peroneal muscular atrophy are described. 1 of them is the first complete autopsy report on this disease. While the number of motor neurons in the spinal cord was grossly normal, the neuropil of the anterior horn exhibited axonal swellings, accumulations of possibly pathological lipofuscin and intra-axonal corpora amylacea. In the muscles, changes were partly those of neurogenic atrophy, partly of a primary myopathy. There was also an accumulation of neutral fat in the muscle fibres, mainly of those of type I.
The authors present their anatomo-clinical observation of amnesic syndrome occurring with brain tumoral infiltration. On the clinical level, the disorder is characterized by a memory encoding deficit. Anatomical examination shows a bilateral lesion of the mamillary bodies.
Since the advent of modern methods of neonatal care, intracranial hemorrhage in premature infants, which is usually intraventricular, is probably not as uniformly fatal as generally admitted and the survivors are likely to develop post-hemorrhagic hydrocephalus. This paper is a retrospective study of 11 premature babies born between 1968 and 1972 and diagnosed as having hydrocephalus secondary to neonatal intracranial hemorrhage. Nine of these are still alive and two have died, one at 3 and one at 17 months of age. Eight underwent permanant surgical drainage of hydrocephalus. The perinatal history, laboratory data, clinical evolution, and neurological outcome were studied. Two groups of infants were identified; those with signs of acute neurological deterioration in the neonatal period who had the most severe neurological sequellae (in four cases, periventricular lesions in addition to hydrocephalus were seen on the air study and in one case confirmed at autopsy) and those showing no obvious neurological signs in the neonatal period. Of this latter group, two appear to be developing normally. The therapeutic implications of the findings are discussed.
The authors describe 14 personal cases of progressive supranuclear palsy, 8 of them including a neuropathological study. The analysis of this material confirms the characteristics of this nosological entity, which is now well individualized amongst the apparently idiopathic degnerative diseases of the CNS. The clinical picture was characterized in all cases by a supranuclear opthalmoplegia, a pseudo-bulbar syndrome, an axial dystonia and a 'subcortical' dementia of a particular type. The average duration of the disease was 4 years for the 12 patients followed until death; the first symptoms appeared at a slightly older age than the average reported in the literature. Males are not predominantly affected in our material. Lesions are remarkably homogeneous as to their localisation in all cases but one. The nuclei of cranial curves are moderately involved, the reticular substances throughout the brain stem is more severely effected. In two cases, senile degenerative lesions of the cerebral cortex are associated with subcortical lesions of the progressive supranulcear palsy. No anamnestic or histologic feature is suggestive of any etiology of this disease. L-Dopa with or within a Dopa-decarboxylase inhibitor did after alter neither the patients condition nor the course of the disease.
The authors described the lesions associated with post-traumatic internal hydrocephalus in 4 cases who died after a prolonged post-traumatic coma. The internal hydrocephalus, quite severe in all cases, and the demyelination in the periventricular white matter in 3 cases, are thought to be produced by a chronic increase in the intraventricular pressure, probably secondary to malfunction of circulation and resorption of the cerebro-spinal fluid.
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Abundant neurofibrillary tangles, neuropil threads and plaque neurites constitute the neurofibrillary pathology of Alzheimer's disease. They form in the nerve cells that undergo degeneration in the disease where their regional distribution correlates with the degree of dementia. Each lesion contains the paired helical filament (PHF) as its major fibrous component. Recent work has shown that PHFs are composed of the microtubule-associated protein tau in a hyperphosphorylated state. PHF-tau is hyperphosphorylated on six adult brain tau isoforms. As a consequence, tau is unable to bind to microtubules and is believed to self-assemble into the PHF. Current evidence suggests that protein kinases or protein phosphatases with a specificity for serine/threonine-proline residues play an important role in the hyperphosphorylation of tau. Candidate protein kinases include mitogen-activated protein kinase, glycogen synthase kinase-3 and cyclin-dependent kinase 5, whereas the trimeric form of protein phosphatase 2A is a candidate phosphatase.
The beta-amyloid precursor protein (APP) carries mutations in codons 717 or 670/671, which cosegregate with familial forms of Alzheimer's disease (AD). As an initial step to study the related pathogenetic mechanisms in vivo we have generated transgenic mice expressing APP with these mutations. Several neuron-specific promoters were used to drive expression of human APP cDNAs. Only the Thy-1 promoter yielded transgene expression levels comparable to or above the endogenous mouse levels. Deletion of a 121 bp sequence from the 3' untranslated region of APP appeared to increase mRNA levels. Transgene mRNA was found throughout the brain with highest levels in hippocampus and cerebral cortex. Accordingly, human APP was detected in these regions by Western blotting. Protein levels paralleled mRNA levels reaching or exceeding the amount of endogenous APP. Variable reactivity of human APP in cell bodies was shown by immunocytochemistry. Although our initial histological examinations did not reveal any alterations characteristic of AD, further studied will be required.
A comparative study of the expression of metabotropic glutamate receptor 2/3 (mGluR2/3) was done in the hippocampus of rats and mice after pilocarpine-induced status epilepticus (APISE), and of patients with mesial temporal lobe epilepsy. At 1 day APISE, there was a marked increase in mGluR2/3 immunoreactivity in the stratum lacunosum moleculare (SLM) of CA1 area and in the middle one-third of the molecular layer (MM) of the dentate gyrus. Immuno-electron microscopic study showed degenerating mGluR2/3 positive axons in the SLM of CA1 area at 1 day APISE. From 7 days, mGluR2/3 immunopositive product decreased, and by 31 days APISE, it almost disappeared in two-thirds of the SLM near CA2. In the mouse model at 2 months APISE, mGluR2/3 immunopositive product in two-thirds of the SLM near the stratum radiatum disappeared, and so did in the whole SLM of CA1 area in patients with mesial temporal lobe epilepsy. Neuropharmacological study by intravenous injection of mGluR2/3 agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate [(2R,4R)-APDC] at different doses at 1h during pilocarpine induced status epilepticus showed that (2R,4R)-APDC could not stop seizures and neuronal death in the hilus of the dentate gyrus. The present study, therefore, suggests that the reduction of mGluR2/3 immunopositive product in the SLM of CA1 is a consequence of neuronal loss in either the entorhinal cortex or CA1 area of the hippocampus, and at the dosage range from 12.5 to 600 mg/kg, (2R,4R)-APDC may not be effective in the prevention of seizures or neuronal death in the hilus of the dentate gyrus.
When biomechanical properties of tendons are studied, the technique of clamping the tendons in the testing machine presents a methodological challenge, especially when murine tendons are examined. These short tendons tend to rupture at the transition line to the fixation, leading to false interpretations. Therefore a new clamping technique for investigation of healthy murine Achilles tendons (n = 50) was developed, in which the intramuscular tendon fibers were fixed between two paper strips and the calcaneus was wedged into a conical slot in a wooden block and then mounted in the testing machine (n = 20). This technique was compared with the conventional clamping technique that fixes both ends of the tendon by clamps (n = 15) and an earlier described method that used glue or plastic cement for the fixation of the intramuscular tendon fibers and calcaneus in the testing machine (n = 15). When tested by the new clamping technique, 17 tendons ruptured intratendinously at a mean tensile force of 8.4 +/- 1.1 N. Three Achilles tendons (17%) tore at the site of paper fixation and had to be excluded from investigation. Data from 73% of the measurements fixed by gluing had to be excluded because slippage of the proximal tendon fibers and contamination of the tendon with glue occurred. All the conventionally clamped tendons ruptured at the site of fixation at a mean tensile force of 6.1 +/- 2.3 N (p < .05). This was 30% lower than with the new clamping technique. Thus, the newly developed clamping technique enables investigators to obtain more valid biomechanical studies of the murine Achilles tendon.