3-Phosphoglycerate dehydrogenase deficiency and 3-phosphoserine phosphatase deficiency: inborn errors of serine biosynthesis.
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Biomedical subjects
Publications and source records attributed to M Foulon.
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Serine concentrations were markedly decreased in the cerebrospinal fluid of two brothers with congenital microcephaly, profound psychomotor retardation, hypertonia, epilepsy, growth retardation, and hypogonadism. The youngest boy also had congenital bilateral cataract. Magnetic resonance imaging of the brain showed evidence of dysmyelination. Plasma serine as well as plasma and cerebrospinal fluid glycine concentrations were also decreased but to a lesser extent. Treatment with oral serine in the youngest patient significantly increased cerebrospinal fluid serine and abolished the convulsions. In fibroblasts of both patients, a decreased activity was demonstrated of 3-phosphoglycerate dehydrogenase, the first step of serine biosynthesis (22% and 13% of the mean control value). This is an unusual disorder as the great majority of aminoacidopathies are catabolic defects. It is a severe but potentially treatable inborn error of metabolism that has not been previously reported in man.
Effects of wilting of grass prior to ensiling on OM intake, ruminal digestibility, efficiency of bacterial protein synthesis, and amount and composition of duodenal N fraction were examined using four lactating Holstein cows. Direct-cut or wilted grass silages were fed for ad libitum intake and supplemented with 5.0 or 5.3 kg of concentrate, respectively. Milk yield was 18.1 and 21.2 kg/d with direct-cut versus wilted silage, and milk protein and fat contents were 2.63 and 4.60% with direct-cut versus 2.75 and 4.27% with wilted silage, respectively. Wilting of the grass (from 17 to 38% DM) increased OM intake but had no effect on ruminal digestibility. Total N flow and amounts of different AA in proximal duodenum were increased, and the difference was principally of bacterial origin. The efficiency of bacterial protein synthesis in rumen was related to dilution rate of liquid phase and to the time devoted to ruminating. These results indicate that the passage of bacterial protein to the lower digestive tract is a key factor for improving the assimilation of the soluble N fraction of grass silage and that this phenomenon is related to chewing activity.
We report on 2 unusual cases of the campomelic syndrome, the first being a fetus in whom the diagnosis was suspected in the 18th week and confirmed sonographically at 20 weeks. The second case concerns a 5 year old 46, XY girl with an exceptional longevity and a relatively favorable evolution.
Spring grass consisting of Lolium perene L. (81%), Poa pratensis L. (9%), and annual weeds (5%) was stored as direct-cut or as wilted silage and used in feeding trials to determine the effects of wilting on N utilization. Six mature Friesian cattle, fitted with rumen and simple duodenal cannulae, were fed the silages for ad libitum intake in a crossover design consisting of two 49-d periods. Wilting increased intake of organic matter and decreased ruminal apparent digestibility or organic matter and whole tract apparent digestibilities of organic matter, NDF, and total N. Rumen degradability of silage N was increased by wilting (.7 vs. .67). Direct-cut silage, in comparison with wilted silage, provide (g/d) less N intake (232 vs. 286) and lower duodenal flows of total N (215 vs. 293), non-NH3 N (202 vs. 280), microbial N (111 vs. 177), and total amino acids (1056.8 vs. 1342.7). Duodenal flows of NH3 N and undegraded N were not different between silages. Efficiency of bacterial N synthesis in rumen was higher for wilted than for direct-cut silage (32.3 vs. 21.4 g N/kg organic matter apparently digested in rumen). It was concluded that wilting increase silage intake, rumen bacterial synthetic efficiency, and duodenal flow of non-NH3 N in cattle.
Congenital dysphasia is a developmental speech disorder not explained by deafness, phonation disorder, mental retardation, neurologic lesion, or psychiatric disease. The existence of brain lesions has often been postulated but conventional investigations fail to demonstrate any cerebral abnormality. By means of [99mTc]hexamethyl-propyleneamine oxime (HM-PAO) brain single photon emission computed tomography (SPECT) we have studied 14 children suffering from congenital dysphasia. The brain computed tomographic scan was normal in all cases. In two patients with expression impairment the SPECT study demonstrated a hypoperfusion in the inferior frontal convolution of the left hemisphere, involving the Broca's area. In nine of 12 patients with global dysphasia (deficits in both comprehension and expression), SPECT study showed two hypoperfused areas: an abnormality in the left temporoparietal region and a hypoactivity in the upper and middle areas of the right frontal lobe. These results suggest that congenital dysphasia could be due, like acquired aphasia, to specific impairment of the language cerebral areas and that brain SPECT studies with [99mTc]HM-PAO could be useful for a better comprehension of the physiopathology of these disorders.
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Three ketophosphonium salts containing a morpholino group were prepared and evaluated for their neuromuscular blocking effect. Solution and crystal conformations were studied. An attempt was made to explain, in structural terms, different activity levels in connection with the interatomic distances.
Various 2-alkyl-alpha-methyl- and 2-alkylindan-5-acetic acids have been prepared. The acids, which can exist in two diastereoisomeric forms that cannot be separated by crystallization or chromatography, can be analyzed in their mixture by NMR in the presence of Eu(dpm)3. It has been possible to reconstitute the two pure racemic 2-isopropyl-alpha-methylindan-5-acetic acids from their enantiomers obtained after resolution of the mixtures through salts with various active bases. The relative configuration of the two asymmetric centers of one of the diastereoisomers salts with various active bases. The relative configuration of the two asymmetric centers of one of the diastereoisomers has been determined by X-ray crystallography. The absolute configurations of the resolved acids have been established by a comparative study of their CD curves. The antiinflammatory and analgesic properties of these compounds as functions of their structure and stereochemistry are discussed.
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In the last five years, 244 children with head trauma were observed. An early post-traumatic epilepsy was present in 11% of the patients. This complication was more frequent in children less than six years of age or presenting a previous neurological history. Early posttraumatic epilepsy was rarely associated with brain concussion and frequently with cerebral contusion. An intracranial haematoma was not encountered in the absence of the classical signs of expanding space occupying lesion.