Biochemical neuropathology of Parkinson's disease.
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Biomedical subjects
Publications and source records attributed to B Berger.
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Changes in cerebral catecholaminergic pathways in Alzheimer type dementia would appear to involve both the noradrenergic and the dopaminergic system in their sub-cortical and cortical distribution, but the essential information currently available involves the noradrenergic innervation of the cerebral cortex. Involvement of this system was first detected by the authors using fluorescence histochemistry on biopsy specimens. In addition to the notable decrease in noradrenergic axons, three types of changes were seen: irregular axonal swelling with neurotransmitter diffusion phenomena, appearances of axonal interruption and, specific to the three cases of pre-senile form of Alzheimer's disease which were studied, the presence of large spherical or fusiform dilatations on the axonal endings, close to senile plaques. Thus histochemical study indicates the possibility of complex involvement, not only of synthesis of the neurotransmitter, but probably also of other properties of the noradrenergic axons: axonal flow, membrane permeability and hence, possibly liberation, uptake and storage of the mediator. These histochemical findings have been confirmed by other teams, who have demonstrated a neuronal loss of 20 to 80% in the locus coeruleus, a nucleus providing the cortical noradrenergic bundle. In addition, biochemical estimations have revealed either a severe reduction of the order of 90% in endogenous noradrenaline (3 personal cases), or a fall of 20 to 45% (cases from the literature), in relation with the method of biopsy or autopsy specimen and the form of pre-senile or senile dementia.(ABSTRACT TRUNCATED AT 250 WORDS)
In 51 patients with alcohol-induced liver injury glucose tolerance and insulin incretion were followed under alcohol abstinence over a period of 4 weeks. In 63% of the cases a pathologic glucose tolerance was found at the beginning. After 4 weeks, when the biochemical liver parameter had become normal, glucose tolerance also returned to normal. The serum insulin levels, in contrast, did not develop any changes. Thus, glucose tolerance improved under unchanged absolute insulin concentrations. From these results, we suggest an insulin resistance in cases of active alcoholic liver injury being reversible under the improvement of liver function during alcohol abstinence.
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We studied the effects of coronary recanalization on arrhythmogenesis in patients undergoing intracoronary thrombolysis during the early hours of myocardial infarction. Catheterization, ventriculography, coronary angiography, and intracoronary streptokinase infusion were performed in 22 patients. Twenty-one of 22 had thrombotic total occlusion of the infarct-related transient thrombolysis with reocclusion by the end of the procedure. In 12 of these 17 patients, restoration of antegrade coronary flow was accompanied by transient arrhythmia. In these 12 patients coronary angiography within seconds of onset of arrhythmia showed vessel patency in a previously totally occluded coronary artery. Two additional patients developed arrhythmias during streptokinase infusion but after reperfusion had already been established. Accelerated idioventricular rhythm was most often noted. Sinus bradycardia and atrioventricular block with hypotension occurred during restoration of flow in arteries supplying the inferoposterior left ventricle. These arrhythmias may be useful noninvasive markers of successful reperfusion during thrombolytic therapy in acute myocardial infarction.
The immunocytochemical localization of tyrosine hydroxylase (TH) and methionine-enkephalin (met-enkephalin) was determined at two representative caudal and rostral levels of the human mesencephalon. Four main groups of catecholaminergic neurons were delineated, situated in the substantia nigra and the lateral, ventromedial and dorsomedial tegmentum, extending over several cytoarchitectonic divisions. They matched fairly well the dopaminergic cell groups described in monkey midbrain. TH-like immunoreactivity and neuromelanin were closely related in neurons of substantia nigra, but less so in the other groups. A widespread met-enkephalinergic innervation was observed in most areas containing catecholaminergic neurons. It followed a characteristic pattern: homogeneous and very dense in the lateral and posterior portions of substantia nigra; patchy and less dense in the other areas, the medio-ventral and periaqueductal gray being only sparsely innervated, in contrast to observations in rodents. Dopaminergic cell bodies surrounded by met-enkephalinergic varicosities were seen in most groups, particularly in the lateral substantia nigra and medioventral tegmentum. The topography of met-enkephali-like immunoreactive terminals in the substantia nigra was reminiscent of the distribution of neostriatal and pallidal afferents.
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Forty-four patients with acute transmural myocardial infarction underwent cardiac catheterization 4.7 +/- 1.3 hours (+/- SD) after the onset of persistent chest discomfort. Thirty-nine patients had total occlusion of infarct-related vessels; 27 of these 39 had successful intracoronary thrombolysis. Twenty of these 27 patients (74%) had reperfusion arrhythmia. Accelerated idioventricular rhythm was most often observed with reperfusion of all myocardial zones, while sinus bradycardia and hypotension accompanied reperfusion of the inferoposterior left ventricle. Three patients with spontaneous accelerated idioventricular rhythm had patient, stenosed, infarct-related vessels on the initial coronary angiogram. Patients with unsuccessful intracoronary thrombolysis did not demonstrate these specific arrhythmias. While there is rapid control of injury current with successful intracoronary thrombolysis, Q waves develop rapidly after reperfusion; however, in the days after intracoronary thrombolysis, there is a decline in Q wave with partial regrowth in R wave amplitude in some patients. Thus, specific arrhythmias, most notably accelerated idioventricular rhythm, are useful markers for the occurrence and timing of successful coronary arterial recanalization. In addition, rapid control of injury current and partial regrowth of R waves are electrocardiographic markers of myocardial salvage.
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A precise topographical analysis of the distribution of tyrosine hydroxylase-like immunoreactive processes was performed in the frontal, cingular and parietal cortex of the rat during late embryonic and early postnatal life. Until birth, labeled processes were only observed in the restricted cortical areas known to receive a dopaminergic innervation in the adult brain. Their distribution differed markedly from that of noradrenergic fibers as identified by their dopamine-beta-hydroxylase-like immunoreactivity. Thus we considered TH-like immunoreactivity to be a selective marker of the cortical dopaminergic innervation during late fetal life, at least with the antibody we used. With this marker, dopaminergic fibers were first detected in the anterior frontal cortex at day 16 of embryonic life (E16). They developed as two bundles passing medially and laterally to the ventricular layer without penetrating it. From E20 on, the terminal fields extended to the cingular and rhinal cortex, still being restricted to the intermediate zone. No fibers were visible in the lateral and dorsal frontal cortex at this time, nor in the cortical plate and molecular layer in any cortical area. At E21, rare labeled fibers were seen in the molecular layer of the medial frontal and cingular cortex. After birth, the terminal fields of the TH-containing fibers extended further caudally in the cingular cortex and also superficially in the cortical plate. Moreover, labeled axons now also appeared in the lateral frontal and parietal cortex where their density gradually increased. At P14, two different patterns of distribution were observed: a high density of TH-positive fibers in the cortical areas known to receive a dopaminergic innervation; a low density of fibers in the other cortical areas which represented noradrenergic fibers. Indeed these TH-containing presumed noradrenergic fibers were absent at P14 following a bilateral destruction of the locus coeruleus in 4-day-old pups.
In 13 and 15 day-old mouse embryos mesencephalic dopaminergic neurons could already be visualized at the level of the mesencephalic flexure by tyrosine hydroxylase immunocytochemistry at day 13. At this time, noradrenergic cells in the locus coeruleus area were not detectable. In most in vitro experiments, dissociated mesencephalic cells of 13 day-old embryos were grown in presence of serum. Four approaches were used to identify the dopaminergic neurons in vitro: fluorescence histochemistry of newly taken up exogenous norepinephrine, radioautography after labelling with (3H) dopamine, tyrosine hydroxylase-like immunoreactivity and fluorescence histochemistry of endogenous stores of catecholamines. Control experiments performed at various times in vitro with selective inhibitors of amine transport into dopaminergic, noradrenergic and serotoninergic neurons indicated that only dopaminergic neurons were detected by these various approaches, noradrenergic neurons being virtually absent from the cultures. The uptake of exogenous norepinephrine was detected already 24 h after plating and preceded the appearance of tyrosine hydroxylase-like immunoreactivity (48 h). The number of neurons revealed by these two techniques increased up to 4 and 10 days, respectively. Endogenous stores of dopamine were only seen after three weeks in vitro by fluorescence histochemistry. At this time, the same number of neurons was revealed whatever the method used. The presence of striatal target cells (co-cultures) affected neither the sequential appearance of the markers nor the number of dopaminergic cells. The two main types of dopaminergic neurons (fusiform and multipolar) described in vivo both in the substantia nigra (A9) and the ventral tegmental area (A10) of adult animals were identified in vitro and their development into well-differentiated neurons can be followed for up to six weeks. This in vitro system seems, therefore, to be particularly suitable for biochemical and electrophysiological studies of these dopaminergic neurons.
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An original method is reported for the radioautographic visualizing of dopaminergic axons terminals in the rat central nervous system. This method is based on an in vitro labelling with either tritiated norepinephrine or dopamine under conditions of specificity previously established by fluorescence histochemistry. The immobilization of [3H]catecholamines in their sites of uptake and storage during post-fixation for electron microscopic processing was ensured by the use of osmic acid vapours instead of osmic acid solution. Selective labelling of the dopaminergic fibers may be achieved throughout large brain sections and the technique should be applicable to human biopsy material.
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A 4-year-old child is described who suffered an unsuspected myocardial contusion which led to the formation of a ventricular aneurysm 2 months after an automobile accident. Electrocardiography, thallium scanning, myocardial enzyme assays, two-dimensional echocardiography and, when indicated, cardiac catheterization, may aid in the early diagnosis of cardiac contusions. In the patient presented, resection of the aneurysm 6 months postinjury was followed by elimination of almost all the mitral regurgitation originally present and good cardiovascular function.
A 12-year-old girl developed posterior scleritis and many detachments of the retinal pigment epithelium. Computed axial tomographic findings, reported in posterior scleritis for the first time, disclosed thickening of the posterior sclera. Computed axial tomography appears to be a sensitive test for the diagnosis of posterior scleritis.
In Escherichia coli, the additon of ethanol resulted in the synthesis of an increased proportion of phospholipids containing two unsaturated fatty acids. The addition of hexanol resulted in the opposite effect, an increase in the proportion of monounsaturated molecular species. The alcohol-induced changes were quantitatively similar to those caused by changing growth temperature. These results suggest that both adaptation to temperature and alcohol-induced changes in lipid composition share some common regulatory features.