[Pasteur's personality illustrated by events in his life].
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Biomedical subjects
Publications and source records attributed to P Sourander.
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The effect of severe protein deprivation and subsequent nutritional rehabilitation on the fibre size and mitochondrial enzyme activity of the extensor digitorum longus (EDL) and soleus muscles of the young rat has been examined. Protein deprived rats showed atrophy of type 2 fibres predominantly, reduced histochemical activity of succinic dehydrogenase (SDH) and reduced biochemical activity of citrate synthase. Nutritional rehabilitation indicated by resumption of the original body weight resulted in complete restitution of the weight of the muscles and the size of type 1 and type 2 fibres, but not of the activity of SDH and citrate synthase. The results indicate that regarding size, type 2 fibres tend to be more influenced than type 1 fibres by the nutritional supply. The mitochondrial enzyme activity which is decreased by protein deprivation does not regain the normal levels as quickly as the muscle fibres resume their normal size.
The specific gravity of the cerebral cortex of normal and protein-deprived rats aged 15, 21 and 25 days was determined. The increase in specific gravity seen in control rats in the course of their development was reduced in protein-deprived rats in the course of the period between 15 and 21 days of age. The results are in agreement with previous reports on delayed maturation of the brain in protein-deprived rats and indicate that determination of brain specific gravity may serve as a suitable screening method in situations when a disturbed brain maturation is suspected.
The influence of maternal protein deprivation on body and brain growth and on serum immunoreactive insulin-like growth factor I (IGF-I) levels was examined in rats during development. The offspring of protein-deprived mothers were significantly growth-retarded postnatally and showed an altered developmental pattern of serum immunoreactive IGF-I levels. In contrast to control animals, between days 5 and 20 postnatally, a significant elevation in serum immunoreactive IGF-I levels which peaked at day 15 was found. However, in adult growth-retarded rats a significant reduction in serum immunoreactive IGF-I levels was found. These findings suggested the preweaning period to be critical for the development of the mature somatomedin system.
Previous studies on the toxic effects of lead on the brains of young animals have shown damage to the blood-brain barrier (BBB) which in severe forms appears as hemorrhagic encephalopathy. In those studies the doses of lead have been of such magnitude that lead-induced anorexia resulting in growth retardation has contributed to the extent of the injury (Sundström et al. 1984). The growth retardation can be prevented by using low lead doses (Sundström et al. 1983). Consequently, we have examined to which extent the BBB is injured in suckling rats with low dose lead encephalopathy. This was done by testing the permeability of the BBB to plasma proteins and assessing the possible occurrence of vasogenic edema by measuring the specific gravity of brain tissue. Low dose lead encephalopathy was induced by daily i.p. injections of lead nitrate 10 mg/kg body weight (b.wt.) for the first 15 days. The lead contents of the blood and homogenates of the cerebrum and cerebellum were assayed by atomic absorption spectrophotometry. The brains were examined at 15, 20, or 30 days of age. When Evans blue-albumin (EBA) was injected i.v. 2 h before killing, most 15-day-old rats exposed to lead displayed a bluish discoloration in their cerebellum. Microscopically, red fluorescence of EBA was seen in the blue-stained regions. Immunohistochemically, extravasation of albumin, fibrinogen, and fibronectin was demonstrated as positive staining in the cerebellar cortex, with diffuse spread to the white matter of the corresponding folium.(ABSTRACT TRUNCATED AT 250 WORDS)
The optic nerve of normal (C) and protein deprived (PD) adult rats was examined by morphometry and biochemistry. The mean cross-sectional area of the optic nerve was reduced by 15% and the number of axons per unit area increased by 17% in the PD rats. Calibre spectrum analysis of axons revealed a reduction in median diameter from 0.49 micron in controls to 0.45 micron in PD rats. The number of axons with a diameter larger than 1 micron was reduced by 35% in PD rats. These reductions were probably due to a general reduction in size, since the calculated total number of axons in the optic nerve was almost identical in C and PD rats (126 X 10(3) and 124 X 10(3), respectively). The increased packing density of axons in the nerve was not only due to thinner axons. The biochemical measurements showed a marked reduction in myelin basic protein in the optic nerves of PD rats, without an alteration in the composition of the total protein. This confirms the persistent hypomyelination which has been reported previously in other malnutrition models. The possible relations between the structural and biochemical changes affecting optic nerve fibres and physiological findings on cortical visual evoked response and on optic nerve in vitro in PD rats are discussed.
Most studies on lead toxicity in the suckling rat have been performed with doses leading to growth retardation. In a previous paper ( Sundstr öm et al. 1983), the effects of different lead doses on normal suckling rats were described. The dose of 10 mg/kg body weight daily given on days 1-15 pp produced minute hemorrhagic lesions on day 15 in the cerebellum, whereas rats given 5 mg/kg body weight daily lacked microscopically discernible pathologic changes in the brain. None of these groups exhibited growth retardation. To further elucidate the association between lead encephalopathy and malnutrition, lead was administered to protein-deprived suckling rats. Protein deprivation was achieved by a diet with 50% reduction of protein content. The mothers of the pups were fed this diet from 2 weeks before conception throughout the experiment. Experimental animals were injected i.p. with 5 mg or 10 mg lead nitrate/kg b.wt. daily. Littermates, injected with vehicle without lead nitrate served as controls. Protein-deprived rats without either treatment were "external" controls. Animals were killed at 10, 15, and 20 days age for determination of lead content in blood and brain and for light-microscopic examination. The protein-deprived rats given 10 mg/kg b.wt. daily were growth-retarded as compared to unexposed protein-deprived rats. The mortality was almost 100% at 15-20 days pp. At 15 days, the cerebellum of these rats showed abundant hemorrhages, and the cerebrum was also hemorrhagically discolored. Protein-deprived rats given 5 mg/kg b.wt. daily did not differ significantly from unexposed protein-deprived rats with regard to body weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)
Ten autosomal recessive/sporadic cases of hereditary motor and sensory neuropathy type I (HMSN I), nine of which originated from the northern part of Sweden, were included in the study. Parents were free from neurologic symptoms. Motor and sensory conduction velocity was normal when recorded, i.e., in 19 and 17 parents, respectively. Sural nerve biopsies from the ten cases revealed a varying degree of onion bulb formation. In eight of the cases the onion bulbs consisted of abundant basement membranes, whereas the Schwann cells were few and sometimes lacking. There were in some cases considerable differences between separate fascicles as to the loss of myelinated nerve fibers. In the six biopsies in which teasing was performed signs of present and previous demyelination were noticed. Numerous internodal segments were abnormally thin with reference to their length. In many such segments there were marked local thickenings of the nerve fiber. In cross sections the probable counterparts to these thickenings were nerve fibers with unduly thick myelin sheaths and complex folding of the myelin. Ultrastructural axonal changes were seen in the majority of the cases. The pathogenetic and diagnostic implications of the present findings are discussed.
The Norrbottnian type of Gaucher disease is characterized by infantile or juvenile onset and variable degrees of neurological symptoms, some of which develop only after splenectomy. A full neuropathological description of this type of Gaucher disease has not been reported previously. The brains of five patients were examined morphologically and biochemically. All presented typical accumulations of glucosylceramide storing cells in the adventitia of vessels in the cerebral and cerebellar sub-cortical white matter (s.c.w.m.). There were differences between the five cases with regard to the accumulation of adventitial storage cells and to the fatty acid pattern of the glucosylceramide isolated from the s.c.w.m., which implicate that the accumulation of glucosylceramide in adventitial cells in the brain is dependent on the generalized lipid storage process and enhanced by splenectomy. Loss of neurones and myelin was noted in the vicinity of accumulations of storage cells in two cases. The five cases showed varying degrees of nerve cell loss, satellitosis and neuronophagia. Lipofuscin with simple and complex lipids but no glycolipids could be demonstrated in neurones light-microscopically. Ultrastructural examination revealed inclusion bodies with bilayers in neurones of the cerebral and cerebellar cortex, dentate nucleus and pons. Because of the bilayered structure of Gaucher cell inclusions the bilayers in neurones are assumed to be formed by glucosylceramide. The fatty acid composition of glucosylceramide isolated from cerebral cortex in all cases suggested that cerebral gangliosides were its main precursor. The highest levels of psychosine (glucosylsphingosine) were seen in the cases with the most advanced nerve cell loss. The morphological and biochemical findings indicate that the neuronopathic process is associated with accumulation of glucosylceramide and psychosine in neurones.
Information on body temperature is frequently lacking in metabolic studies on normal and malnourished suckling rats although differences in their thermoregulatory efficiency may be expected. The aim of the present study was to evaluate the effect of different ambient temperatures on the rectal temperature of litters of normal and protein deprived rats to establish the ambient temperatures at which a normal rectal temperature can be expected at various postnatal ages. The offspring of normal rats and rats subjected to a dietary reduction of 50% of the protein intake were examined 10 days to 30 days postnatally. The pups were transferred from the nest cage to an incubator: the rectal temperature was measured immediately after transfer to the incubator and 30 and 60 min later at ambient temperatures of 35, 30 and 25 degrees C. Up to 15 days of age control pups showed a fall in rectal temperature after the short exposure to room temperature (22 degrees C) needed for transfer. A similar fall of rectal temperature was recorded in the malnourished pups up to 25 days age. The effects of the ambient temperatures on the malnourished pups indicated a delay in the control of body temperature of some 10 days. This is in agreement with a previous report on semi-starved rats (Heim & Szelenyi 1965). The conditions for the maintenance of a normal rectal temperature in litters of normal and malnourished suckling rats separated from their mother are out-lined.
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The clinical, genetic, and morphological features of a previously unknown progressive neuropsychiatric disease are presented. By genealogical investigation of the background of an uncharacteristic case of presumed organic psychosis, we traced 71 relatives from four generations. The anamnestic data showed various combinations of psychiatric symptoms (depression, anxiety, aggressiveness, and severe dementia), neurological symptoms (impaired balance with retropulsion, hyperkinesia, and epilepsy), and somatic symptoms (gastrointestinal disorders, arthritis, and gynaecological problems) in 17 (11 dead and 6 living) members of the family. Age at onset varied between 8 and 60 years. Some patients rapidly developed severe dementia and died a few months after the onset of symptoms, while in others the course was prolonged with dementia over several decades. The genetic interpretation indicated an autosomal dominant inheritance with possible full penetrance but widely variable expressivity. Morphological studies were performed on the central nervous system of four decreased family members (three siblings and their maternal uncle). The same type of widespread leucoencephalopathy was seen in the four autopsy cases. It was characterised by degeneration and loss of myelin sheaths and axons, occurrence of numerous neuroaxonal spheroids in the affected white matter, accumulation of lipid-laden macrophages, and gliosis. The bilateral, frontal, fronto-parietal, and temporal locations of the most pronounced, diffusely demarcated lesions corresponded fairly well to the symptoms of an organic psychosyndrome with its main substrate in the forebrain. For this new clinico-pathological entity, the name "hereditary diffuse leucoencephalopathy with spheroids" (HDLS) is proposed. As a working hypothesis, it is suggested that not only genetic, but also immunological and possible endocrine factors may contribute to the development of the disease.
An ultrastructural and morphometric study was performed on sural nerve biopsies of four industrial spray painters (35-59 years) and 11 controls (6-64 years). No difference could be shown in spray painters and age-matched controls as to the number of myelinated nerve fibres per area, their size distribution, variation of internodal length along single nerve fibres or the ratio between the number of myelin lamellae and the axon circumference. There was marked scattering of the two latter parameters in older exposed and and control individuals. The distribution of NADH2-tetrazolium reductase activity was similar in exposed and control cases. The general ultrastructural appearance of nodal-paranodal regions in controls conformed with that noted in experimental animals. The overall ultrastructural organization and age-related changes of nerves of exposed cases were similar to those of control cases except for a presence of paranodal axonal mitochondria which contained glycogen-like particles in exposed cases. In one exposed case abundant dispersed or clustered glycogen-like particles were seen in the paranodal axoplasm. These findings are suggested to be an effect of chronic exposure to organic solvent vapours. Ageing seems, however, to have a much greater impact on the morphology of the sural nerve fibre than occupational exposure to organic solvent.
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Rats were reared on a standard diet up to the age of 6 weeks when they were divided into two groups. One was fed on a diet containing 14% protein and the other on a diet with only 1.5% protein. The size of the various fibre types of the EDL muscle of both groups was assessed at 6 and 25 weeks of age. All the fibre types of protein-deprived rats were smaller compared to the age-matched controls, the difference being most evident in the 2B fibres. In the protein-deprived rats the 2B fibres atrophied while the type 1 and type 2A fibres simply failed to grow. Histochemical and ultrastructural examination revealed a marked reduction of the subsarcolemmal mitochondria after prolonged protein deprivation; normally large accumulations of mitochondria are seen preferentially in type 2A fibres.
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