[Respiratory distress syndrome in an adult secondary to Mycoplasma pneumoniae infection].
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Adult↗
Biomedical subjects
C Lemaire
Publications and source records attributed to C Lemaire.
Combined study of cerebral glucose metabolism and [11C]methionine accumulation in probable Alzheimer's disease using positron emission tomography.
There is a characteristic decrease in glucose metabolism in associative frontal and temporo-parietal cortices of patients suffering from Alzheimer's disease (AD). The decrease in metabolism might result from local neuronal loss or from a decrease of synaptic activity. We measured in vivo [11C]methionine accumulation into proteins with positron emission tomography (PET) to assess cortical tissue loss in AD. Both global regional activity and compartmental analysis were used to express [11C]methionine accumulation into brain tissue. Glucose metabolism was measures with [18F]fluorodeoxyglucose and autoradiographic method. Combined studies were performed in 10 patients with probable AD, compared to age-matched healthy volunteers. There was a significant 45% decrease of temporo-parietal glucose metabolism in patients with AD, and frontal metabolism was lowered in most patients. Temporo-parietal metabolism correlated to dementia severity. [11C]methionine incorporation into temporo-parietal and frontal cortices was not significantly decreased in AD. There was no correlation with clinical symptoms. Data suggest that regional tissue loss, assessed by the decrease of [11C]methionine accumulation, is not sufficient to explain cortical glucose hypometabolism, which reflects, rather, reduced synaptic connectivity.
Aged↗
Immune system-dependent and -independent replication of the scrapie agent.
Using the severe combined immunodeficiency (SCID) mouse model, we investigated the requirement of the immune system for the development of scrapie after peripheral inoculation. A total of 33% of SCID mice, all but one immunologically reconstituted SCID mice (93%), and all CB17 control mice developed the disease. PrPres was detectable in the brains of all diseased animals and in the spleens of reconstituted SCID and CB17 control mice but not of the diseased non-immunologically reconstituted SCID mice. The immune system appears to be a primary target in the pathogenesis of scrapie, but direct spread to the central nervous system from the peritoneum via visceral nerve fibers can probably also occur.
Animals↗
Genetic engineering of snake toxins. The functional site of Erabutoxin a, as delineated by site-directed mutagenesis, includes variant residues.
Using site-directed mutagenesis, we previously identified some residues that probably belong to the site by which Erabutoxin a (Ea), a sea snake toxin, recognizes the nicotinic acetylcholine receptor (AcChoR) (Pillet, L., Trémeau, O., Ducancel, F. Drevet, P., Zinn-Justin, S., Pinkasfeld, S., Boulain, J.-C., and Ménez, A. (1993) J. Biol. Chem. 268, 909-916). We have now studied the effect of mutating 26 new positions on the affinity of Ea for AcChoR. The mutations are F4A, N5V, H6A, Q7L, S9G, Q10A, P11N, Q12A, T13V, T14A, K15A, T16A, delta S18, E21A, Y25F, Q28A, S30A, T35A, I36R, P44V, T45A, V46A, K47A, P48Q, I50Q, and S53A. Binding affinity decreases upon mutation at Gln-7, Gln-10 and to a lesser extent at His-6, Ser-9 and Tyr-25 whereas it increases upon mutation at Ile-36. Other mutations have no effect on Ea affinity. In addition, new mutations of the previously explored Ser-8, Asp-31, Arg-33, and Glu-38 better explain the functional role of these residues in Ea. The previous and present mutational analysis suggest that the "functional" site of Ea covers a homogeneous surface of at least 680 A2, encompassing the three toxin loops, and includes both conserved and variant residues. The variable residues might contribute to the selectivity of Ea for some AcChoRs, including those from fish, the prey of sea snakes.
Amino Acid Sequence↗
Mutations in the mitochondrial split gene COXI are preferentially located in exons: a mapping study of 170 mutants.
We have analysed the precise location of a large number (170) of mutations affecting the structural gene for subunit I of the cytochrome c oxidase complex. This gene, COXI, is 12.9 kb long and the major part of the sequence (i.e. 11.3 kb) is composed of introns. Several conclusions can be drawn from this study: (1) A significant proportion (84/170) of the mutations cannot be assigned to a single position within the gene by deletion mapping, in spite of clearly being located in it. These mutations are probably large deletions or multiple mutations. (2) Four mutants carry distant double mutations, which have been individually localized. (3) Eighty-two mutants have lesions that are restricted to very short regions of the gene and we therefore conclude that they are most probably due to single hits; amongst these single mutations, 41 are unambiguously located in exons and 28 in introns. This result implies that, at least in this particular split gene, the probability of selection of a mutant phenotype in an exon is, on the average, 13.3 times greater than in an intron, in spite of the existence, within most of these introns, of open reading frames specifying intronic proteins. The evolutionary significance and biological implications of these results are discussed.
Base Sequence↗
Expression of alkaline phosphatase by a B-cell hybridoma and its modulation during cell growth and apoptosis.
The 7TD1 B-cell hybridoma was found to spontaneously express alkaline phosphatase (ALP), an enzyme which is produced by splenic B lymphocytes once optimally activated. Determination of ALP levels during cell growth and departure to apoptosis showed fluctuations. Following a temporary increase within the first 24 h, enzyme expression was maintained at high levels during the early proliferation stage, and then declined from 3 to 4 days in mid-exponential phase to basal levels at day 6 when living cells were no longer detectable and the apoptotic process was completed. The protein synthesis inhibitor, cycloheximide (1 microg/ml), decreased ALP production while stimulating a strong apoptosis of 7TD1 cells, within 4 h. Aphidicolin (1 microg/ml) maintained ALP production and provoked a release of ALP activity into the surrounding medium; it also induced apoptosis, but with a 24 h delay. Quantification of apoptosis and ALP expression by flow cytometry, after simultaneous staining of DNA with Hoechst 33342 and ALP with naphthol AS-TR phosphate/Fast Red RC fluorescent reagent, revealed cell cycle modulation of ALP expression, its activity increasing as 7TD1 cells progressed from G1 phase into S and G2/M phases of the cell cycle in control as well as in drug-treated cells. Kinetics of drug-induced apoptosis and higher expression of ALP associated preferentially with active cell growth during the prevention stage of apoptosis suggested a possible link between cellular ALP expression and cell survival.
Alkaline Phosphatase↗
Osteoarthritis staging: comparison between magnetic resonance imaging, gross pathology and histopathology in the rhesus macaque.
Although osteoarthritis (OA) is the most common cause of articular skeletal disability in humans, assessing progression (staging) with noninvasive methods remains a major clinical problem. Using the rhesus macaque animal model, the objective of this study was to compare OA staging by noninvasive magnetic resonance imaging (MRI) against gross pathology and histopathology. Right knee joints from 18 rhesus macaques were used in this study. Using a four-point ordinal scale for each of the above-mentioned modalities, the lateral and medial femoral condyle and tibial plateau of each knee joint was independently scored for OA severity, i.e. normal, mild OA, moderate OA and severe OA. Correlation between each staging system was performed using Stuart's Tau-c correlation coefficient. By our criteria, MRI staging correlated as well with gross pathology (tau = 0.75) and histopathology (tau = 0.80) as did gross pathology with histopathology (tau = 0.78). Our study shows that MRI is a promising noninvasive modality to evaluate the severity of OA. MRI appears to be sensitive for demarcating the presence and extent of focal OA cartilage lesions. However, at this time, while MRI is sensitive for detecting OA change it cannot distinguish between certain lesions such as superficial cartilage matrix fibrillation and hypertrophy both of which show elevated signal intensity.
Animals↗
Serotonin 5HT2 receptor imaging in the human brain using positron emission tomography and a new radioligand, [18F]altanserin: results in young normal controls.
Changes in serotonin-2 receptors have been demonstrated in brain autopsy material from patients with various neurodegenerative and affective disorders. It would be desirable to locate a ligand for the study of these receptors in vivo with positron emission tomography (PET). Altanserin is a 4-benzoylpiperidine derivative with a high affinity and selectivity for S2 receptors in vitro. Dynamic PET studies were carried out in nine normal volunteers with high-specific activity (376-1,680 mCi/mumol) [18F]altanserin. Arterial blood samples were obtained and the plasma time-activity curves were corrected for the presence of labeled metabolites. Thirty minutes after injection, selective retention of the radioligand was observed in cortical areas, while the cerebellum, caudate, and thalamus had low radioactivity levels. Specific binding reached a plateau between 30 and 65 min postinjection at 1.8% of the injected dose/L of brain and then decreased, indicating the reversibility of the binding. The total/nonspecific binding ratio reached 2.6 for times between 50 and 70 min postinjection. The graphical analysis proposed by Logan et al. allowed us to estimate the binding potential (Bmax/KD). Pretreatment with ketanserin was given to three volunteers and brain activity remained uniformly low. An additional study in one volunteer showed that [18F]altanserin can be displaced from the receptors by large doses of ketanserin. At the end of the study, unchanged altanserin was 57% of the total plasma activity. These results suggest that [18F]altanserin is selective for S2 receptors in vivo as it is in vitro. They indicate that [18F]altanserin is suitable for imaging and quantifying S2 receptors with PET in humans.
Adult↗
Osteoarthritis in rhesus macaque knee joint: quantitative magnetic resonance imaging tissue characterization of articular cartilage.
OBJECTIVE: To assess cartilage matrix quality variation by anatomical location and extent of osteoarthritis (OA) using quantitative magnetic resonance imaging (MRI) and to compare the anatomic MR morphologic features with corresponding histological findings. METHODS: We studied 18 fully encapsulated right knee joints from a population of rhesus monkeys with a high incidence of degenerative arthritis resembling human OA. Relaxation times (T1 and T2) spin density, and cartilage thickness were determined along 8 contiguous anteroposterior segments of articular cartilage. Histological slides, prepared in the same plane as the MR image, were assessed for OA severity. Using a modification of Mankin's OA classification, each quadrant was grouped into normal (0), mild (1), moderate (2), or severe OA (3). Histopathological scores served as the standard and corresponding MR quadrants were classified accordingly. RESULTS: Cumulative results revealed a significant decrease in T1 relaxation time (p = 0.04) and an increase in T2 relaxation time (p = 0.03) in the mild and severe OA groups, respectively. Statistically significant changes in spin density and cartilage thickness measurements were not observed. MR signal intensity abnormalities in selected regions of interest were demarcated and studied histologically. Regions with histological proliferating chondrocytes or fibrillated cartilage showed bright signal intensity on MR images (TR = 3000 ms; TE = 10 ms) and corresponded with elevated T1 and T2 values. Histological regions of collagen condensation showed low signal intensity on MR images (TR = 3000 ms; TE = 10 ms) and corresponded with decreased T1 and T2 relaxation times. CONCLUSION: Topological quantitative MRI relaxation time assessment demonstrates increasing cartilage matrix quality variation with OA progression.
Animals↗
Giant catfish Pangasianodon gigas growth hormone-encoding cDNA: cloning and sequencing by one-sided polymerase chain reaction.
cDNA clones encoding giant catfish (Pangasianodon gigas) growth hormone (GH) have been isolated using a polymerase chain reaction (PCR) strategy. Pairwise combinations of degenerate and general primers allowed for the amplification of regions both 3' and 5' to the point of entry into the message. The amplified PCR products were cloned and sequenced. The cDNA sequence was found to encode a polypeptide of 200 amino acids (aa), including a putative signal peptide of 22 aa. The 5' and 3' untranslated regions of the message are 58 and 515 nucleotides long, respectively. The giant catfish GH displays the highest aa sequence homology with the carp GH, with 80% of sequence identity. Moreover, giant catfish GH has structural features in common with both mammalian and avian GH polypeptides, and also contains the domains of conserved sequence found in other GH.
Amino Acid Sequence↗
Synthesis and biodistribution of [5-131I]iodotropapride: a potential D2 dopamine receptor imaging agent.
[5-131I]Iodotropapride is a benzamidic compound which displays high affinity and selectivity for dopaminergic receptors. It was prepared from the corresponding brominated compound by a nucleophilic substitution with [131I]iodine (t1/2 = 8.02 days, E gamma = 364 keV) based on the use of Cu(I) as catalyst and high specific activity of [131I]NaI. After i.v. injection in rats the tracer crosses the blood-brain barrier (0.42 +/- 0.06% of injected dose in the total brain) and demonstrates a high affinity binding to the striatum. The striatum-to-cerebellum ratio increases with time and reaches values of 9 and 22 at 30 and 120 min after injection, respectively. This specific uptake in the striatum is saturable and can be blocked by pretreatment with different D2 antagonists. When labeled with 123I (t1/2 = 13 h, E1 = 159 keV), the corresponding [123I]iodotropapride may be useful for the investigation of the D2 dopamine receptors in humans with single photon emission computer tomography (SPECT).
Animals↗
Psychophysiological reactions in humans during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture.
Six commercial divers were investigated for neurological and psychosensorimotor responses during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture containing 49% hydrogen. Results showed only moderate neurological symptoms of high-pressure nervous syndrome, whereas the narcotic effect of hydrogen was detectable, as investigated by psychosensorimotor tests. Nevertheless, the divers successfully carried out the main purpose of the operational dive, which was to prove the feasability of such diving methods by connecting specific elements of an offshore oil installation. Finally, these data support the hypothesis that hydrogen can alleviate some of the symptoms of the high-pressure nervous syndrome and can constitute a useful gas for commercial diving, as it decreases the density of the breathing mixture and therefore improves the living conditions, work, and comfort of the divers. Nevertheless, the present results underscore the relevance of research on individual susceptibility to pressure environment regardless of the composition of the breathing mixture.
Adult↗
High-energy phosphate metabolism in a neonatal model of hydrocephalus before and after shunting.
The authors studied the effects of hydrocephalus on the high-energy phosphate metabolism of the brain and the impact of ventriculoperitoneal (VP) shunting on these changes in an experimental model of hydrocephalus. High-energy phosphate metabolism was analyzed using in vivo magnetic resonance (MR) imaging and 31P MR spectroscopy. Hydrocephalus was produced in 34 1-week-old kittens by cisternal injection of 0.05 ml of a 25% kaolin solution. Sixteen litter mates were used as controls. A VP shunt with a distal slit valve was implanted in 17 of the 34 hydrocephalic animals 10 days after induction of hydrocephalus. Both MR imaging and 31P MR spectroscopy were obtained 1 and 3 weeks after either kaolin or distilled water injection. Untreated hydrocephalic animals had marked dilatation of the lateral ventricles and periventricular edema. Magnetic resonance spectroscopy showed a significant decrease in the energy index ratio of phosphocreatine (PCR): inorganic phosphate (PI) and an increase in the PI:adenosine triphosphate (ATP) ratio. There was a direct correlation between the decrease in the energy index and ventricular size. Compared with preoperative scans, shunted animals showed no periventricular edema, and the ventricles decreased in size. Also, PCR:PI and PI:ATP ratios were within the levels of controls. This study suggests that neonatal hydrocephalus results in a mild hypoxic/ischemic insult that is treatable by VP shunting.
Adenosine Triphosphate↗
Enantioselective synthesis of 6-[fluorine-18]-fluoro-L-dopa from no-carrier-added fluorine-18-fluoride.
METHODS: A trimethylammonium veratraldehyde triflate was synthesized and used as a precursor for the asymmetric synthesis of 6-[18F]fluoro-L-dopa. RESULTS: Its nucleophilic fluorination with 18F-fluoride produced by the 18O(p,n)18F nuclear reaction on enriched 18O-water led to the corresponding no-carrier-added [18F]fluoroveratraldehyde (45 +/- 5% EOB). Diiodosilane was used to prepare the corresponding [18F]fluorobenzyl iodide (36.5 +/- 5.3% EOB). Akylation of (S)-1-tert-boc-2-tert-butyl-3-methyl-4-imidazolidinone with this electrophilic agent, hydrolysis and purification by preparative high-pressure liquid chromatography made 6-[18F]fluoro-L-dopa ready for human injection, in a 23% +/- 6% decay-corrected radiochemical yield. The enantiomeric purity and the specific activity were above 96% and 1 Ci/mumole respectively. CONCLUSION: Through this procedure, starting from 250 mCi of 18F-fluoride, multimillicurie amounts (32 +/- 8.5 mCi) of no-carrier-added 6-[18F]fluoro-L-dopa are now available at the end of synthesis (90 min) with a good radiochemical purity (more than 98%).
Chromatography, High Pressure Liquid↗
Differential diagnosis of Alzheimer's disease with PET.
UNLABELLED: PET studies have demonstrated bilateral temporo-parietal hypoperfusion and hypometabolism in probable and definite Alzheimer's disease (AD), a pattern that may help differentiate AD from other dementias. METHODS: To evaluate the diagnostic power of cerebral metabolic distribution patterns for "cortical" degenerative dementias, PET scans obtained from 129 patients referred for differential diagnosis of dementia were analyzed visually. RESULTS: Sixty-five patients had a final clinical diagnosis of probable AD. Ninety-seven percent (97%) of those had abnormal metabolic scans and 94% showed a suggestive pattern of bilateral or unilateral temporo-parietal hypometabolism (with or without frontal involvement). Hypometabolism was unilateral in 23% of patients. Five subjects with a neuropathologically proven diagnosis of Alzheimer's disease had a suggestive metabolic pattern. One of those was an early case with frontal hypometabolism exceeding temporo-parietal involvement. Two patients with Alzheimer's-type dementia had isolated bilateral frontal hypometabolism. CONCLUSIONS: This alternative metabolic pattern may correspond to a non-Alzheimer pathology occurring in 10%-20% of patients suffering from clinically probable Alzheimer's disease. Most of the patients with possible but atypical Alzheimer's-type dementia showed isolated bilateral frontal involvement. This metabolic pattern probably corresponds to different diseases, such as Pick's disease, frontal lobe dementia or progressive subcortical gliosis.
Alzheimer Disease↗
Osteoarthritis in rhesus macaques: assessment of cartilage matrix quality by quantitative magnetic resonance imaging.
To assess cartilage quality with anatomical location and extent of osteoarthritis (OA), magnetic resonance imaging (MRI) of the knee joint from rhesus monkeys was performed. MRI measurements--T1 and T2 relaxation times, proton density and cartilage thickness were taken from 8 equal segments of articular cartilage volumes extending from anterior to posterior edge of 1 mm sagittal slices. To grade the severity of OA in each quadrant of the knee joint a modified Mankin score was applied on the histological sections. Our results suggest that MR relaxation times and proton density values vary with the severity of osteoarthritis.
Animals↗
CO recombination as a probe of the Fe/Cu binuclear centre of terminal protonmotive oxidases.
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Amino Acid Sequence↗
2- and 4-[18F]fluorotropapride, two specific D2 receptor ligands for positron emission tomography: N.C.A. syntheses and animal studies.
Tropapride, (exo)-2,3-dimethoxy-N-[8-(phenylmethyl)-8- azabicyclo[3.2.1]oct-3-yl]benzamide hydrochloride, has been labeled with fluorine-18 at the 2- and 4-positions of its benzylic group. Two synthetic pathways were investigated: the first one required the alkylation of the norbenzyl precursor with 2- or 4-[18F]fluorobenzyl bromide (radiochemical yield of 5% EOB, 180 min); the second method consisted of a reductive amination of norbenzyl tropapride with 2- or 4-[18F]fluorobenzaldehyde (20% EOB, 110 min). In both cases, the specific activity was found to be greater than 1 Ci/mumol (EOS). Animal studies in rats showed the percentage of the injected dose localizing in the whole brain to be 0.6 +/- 0.09 and 0.2 +/- 0.03 at 2 h post injection for the para- and the ortho-[18F]fluoro analogs of tropapride respectively. Cerebral biodistribution studies showed at 4 h a striatum uptake of 5 +/- 0.7% of the injected dose per gram of striatum for the para derivative with a low fixation into the frontal cortex and the cerebellum (% ID/g FC < 0.4 and % ID/g Cb < 0.3). The selectivity of 4-[18F]fluorotropapride for D2 dopaminergic sites was demonstrated through blocking experiments with ketanserin, spiperone and halopemide. The saturability was confirmed by the use of variable specific activities. These preliminary results showed that 4-[18F]fluorotropapride can be considered as a potent radiopharmaceutical for the study of the dopaminergic system with PET.
Animals↗