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Showing papers by "French Institute of Health and Medical Research published in 1989"


Journal ArticleDOI
TL;DR: Description of mapping methods using spherical splines, both to interpolate scalp potentials (SPs) and to approximate scalp current densities (SCDs) with greater accuracy in areas with few electrodes.

2,343 citations


Journal ArticleDOI
TL;DR: The results may indicate that an increased level of lipid peroxidation continues to occur in the parkinsonian nigra up to the time of death, perhaps because of continued exposure to excess free radicals derived from some endogenous or exogenous neurotoxic species.
Abstract: Polyunsaturated fatty acid (PUFA) levels (an index of the amount of substrate available for lipid peroxidation) were measured in several brain regions from patients who died with Parkinson's disease and age-matched control human postmortem brains. PUFA levels were reduced in parkinsonian substantia nigra compared to other brain regions and to control tissue. However, basal malondialdehyde (MDA; an intermediate in the lipid peroxidation process) levels were increased in parkinsonian nigra compared with other parkinsonian brain regions and control tissue. Expressing basal MDA levels in terms of PUFA content, the difference between parkinsonian and control substantia nigra was even more pronounced. Stimulating MDA production by incubating tissue with FeSO4 plus ascorbic acid, FeSO4 plus H2O2, or air alone produced lower MDA levels in the parkinsonian substantia nigra, probably reflecting the lower PUFA content. These results may indicate that an increased level of lipid peroxidation continues to occur in the parkinsonian nigra up to the time of death, perhaps because of continued exposure to excess free radicals derived from some endogenous or exogenous neurotoxic species.

1,373 citations


Journal ArticleDOI
TL;DR: In neurones in which evoked GDPs were blocked by bicuculline, a NMDA‐mediated component was revealed by increasing the strength or the frequency of stimulation, and during the second week of postnatal life, superfusion with bicuciulline induced, as in adult slices, interictal discharges.
Abstract: 1. Intracellular recordings were made from rat CA3 hippocampal neurones in vitro during the first eighteen days of postnatal life. The cells had resting membrane potentials more negative than -51 mV, action potentials greater than 55 mV and membrane input resistances of 117 +/- 12 M omega. An unusual characteristic of these cells was the presence of spontaneous giant depolarizing potentials (GDPs) which were observed during the first eight postnatal (P) days in over 85% of neurones. They were less frequent between P9 and P12 (48%) and disappeared after P12. 2. The GDPs were synchronously generated by a population of neurones; they reversed polarity at -27 mV when recorded with KCl-containing electrodes and at -51 mV with potassium acetate- or potassium methylsulphate-filled electrodes. 3. The GDPs were blocked by bath application of bicuculline (10 microM) or picrotoxin (100-200 microM). Exogenously applied gamma-aminobutyric acid (GABA; 0.2-1 mM) induced at resting membrane potential a bicuculline-sensitive membrane depolarization which reversed polarity at -25 and -51 mV when recorded with KCl- or potassium methylsulphate-filled electrodes respectively. 4. The GDPs were reduced in frequency or blocked by the N-methyl-D-aspartate (NMDA) receptor antagonists DL-2-amino-7-phosphonoheptanoate (AP-7; 50 microM), D(-)2-amino-5-phosphonovalerate (AP-5, 10-50 microM) and (+-)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10-50 microM) or NMDA channel blockers phencyclidine (2 microM) and ketamine (20 microM). 5. Stimulation of the hilus during the first week of life evoked a GDP followed by a hyperpolarization. The GDPs were generated by a population of synchronized neurones and reversed polarity at -27 mV with KCl-filled electrodes and at -52 mV with potassium acetate- or potassium methylsulphate-containing electrodes. 6. Bath application of bicuculline (1-10 microM) or picrotoxin (100-200 microM) reversibly blocked the evoked GDPs in the majority of cells. The NMDA receptor antagonists AP-5 (50 microM), AP-7 (50 microM) and CPP (30 microM) usually reduced the amplitude and the duration of the evoked GDPs. In neurones in which evoked GDPs were blocked by bicuculline, a NMDA-mediated component was revealed by increasing the strength or the frequency of stimulation. 7. During the second week of postnatal life, when spontaneous GDPs were extremely rare or absent, superfusion with bicuculline (10 microM) induced, as in adult slices, interictal discharges. These reversed polarity near 0 mV with KCl- or potassium acetate-containing electrodes and were reduced in amplitude and duration by AP-5 (50 microM).(ABSTRACT TRUNCATED AT 400 WORDS)

1,283 citations


Journal ArticleDOI
TL;DR: Increased levels of total iron in the substantia nigra may cause the excessive formation of toxic oxygen radicals, leading to dopamine cell death, in Parkinson's disease.
Abstract: Levels of iron, copper, zinc, manganese, and lead were measured by inductively coupled plasma spectroscopy in parkinsonian and age-matched control brain tissue There was 31-35% increase in the total iron content of the parkinsonian substantia nigra when compared to control tissue In contrast, in the globus pallidus total iron levels were decreased by 29% in Parkinson's disease There was no change in the total iron levels in any other region of the parkinsonian brain Total copper levels were reduced by 34-45% in the substantia nigra in Parkinson's disease; no difference was found in the other brain areas examined Zinc levels were increased in substantia nigra in Parkinson's disease by 50-54%, and the zinc content of the caudate nucleus and lateral putamen was also raised by 18-35% Levels of manganese and lead were unchanged in all areas of the parkinsonian brain studied when compared to control brains, except for a small decrease (20%) in manganese content of the medial putamen Increased levels of total iron in the substantia nigra may cause the excessive formation of toxic oxygen radicals, leading to dopamine cell death

1,089 citations


Journal ArticleDOI
03 Nov 1989-Cell
TL;DR: It is shown that the N-terminal A/B region of the ER contains an independent constitutive activation function (TAF-1) that exhibits cell type specificity since it activates transcription efficiently in chicken embryo fibroblasts, but only poorly in HeLa cells.

1,031 citations


Journal ArticleDOI
01 Feb 1989-Blood
TL;DR: Data demonstrated a paracrine but not autocrine regulation of the growth and differentiation of myeloma cells by IL-6, which is not the autocrine growth factor of these well-documented human myelomatic cell lines.

803 citations


Journal ArticleDOI
01 Jul 1989-Gut
TL;DR: The index was calculated in 54 patients with active Crohn's disease, before and at the end of a course of corticosteroids: index variations correctly reflected changes in colitis severity as evaluated by the endoscopists.
Abstract: The aim of this study was to develop and validate an endoscopic index for assessing the severity of Crohn's disease. Endoscopic findings were prospectively collected by a multicentre group in 75 patients with Crohn's colitis according to a previously validated procedure. The presence of nine preselected lesions was recorded in the following segments (1) rectum, (2) sigmoid and left colon, (3) transverse colon, (4) right colon, and (5) ileum. In addition the extent of the diseased and ulcerated areas were estimated in each segment. These segmental data were recorded on a standard form, together with the endoscopist's global estimate of lesion severity. A stepwise multiple regression was used to derive an index which was correlated with the endoscopist's global evaluation of lesion severity. Four mucosal lesions: deep and superficial ulcerations, ulcerated and non-ulcerated stenosis, and both estimates of extent involved were selected and weighted to obtain a Crohn's Disease Endoscopic Index of Severity which correlated with the endoscopist's global appraisal of lesion severity (r = 0.83). This index was then prospectively shown to be valid in a further series of 113 colonoscopies (r = 0.81). The index was calculated in 54 patients with active Crohn's disease, before and at the end of a course of corticosteroids: index variations correctly reflected changes in colitis severity as evaluated by the endoscopists (r = 0.72). For endoscopists familiar with the data collection procedure, this Crohn's Disease Endoscopic Index of Severity should be of value in the follow up of patients, especially in clinical trials.

794 citations


Journal ArticleDOI
TL;DR: IicsA, a locus necessary for intra- and intercellular spread, was identified on the Shigella flexneri virulence plasmid pWR100 and shown to express a 120-kDa outer membrane protein, which plays an important role in the interactions established between host cell microfilaments and the bacterial surface, thus leading to intracellular movement.
Abstract: The capacity of Shigella to spread within the cytosol of infected epithelial cells and to infect adjacent cells is critical for the development of infection foci, which lead to mucosal abscesses. Shigella is a nonmotile microorganism that appears to utilize host cell microfilaments to generate intra- as well as intercellular movements, since this movement was inhibited by cytochalasin D and involvement of F-actin was demonstrated by direct labeling of infected cells with the specific dye N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phallacidin. Such movements led to the formation of extracellular protrusions, which may explain cell to cell spread. icsA, a locus necessary for intra- and intercellular spread, was identified on the Shigella flexneri virulence plasmid pWR100. This locus was cloned and shown to express a 120-kDa outer membrane protein, which plays an important role in the interactions established between host cell microfilaments and the bacterial surface, thus leading to intracellular movement.

712 citations


Journal ArticleDOI
21 Dec 1989-Nature
TL;DR: It is shown that the gene for the D2 receptor produces two receptor isoforms by alternative messenger RNA splicing, providing a route to receptor diversity in this family of receptors.
Abstract: Dopamine receptors are classified into D1 and D2 subtypes on the basis of their pharmacological properties and the intracellular responses they mediate. The cerebral D2 dopamine receptor is the target of drugs used to alleviate the main symptoms of schizophrenia. Although it is considered to be a single molecular entity, there is evidence that multiple D2-receptor subtypes exist. A complementary DNA encoding a D2 receptor has recently been cloned and the deduced 415-amino-acid sequence indicates that it belongs to the large superfamily of receptors coupled to G proteins, and that its topology consists of seven transmembrane domains. In this family, the genes are frequently without introns and each is believed to encode a unique polypeptide product. Here we show that the gene for the D2 receptor produces two receptor isoforms by alternative messenger RNA splicing, providing a route to receptor diversity in this family. One isoform corresponds to the D2(415) receptor, but the second contains an additional sequence encoding a 29-amino-acid fragment, defining a novel D2(444) receptor isoform. Expression of the two isoforms is tissue-specific, and both are regulated by guanyl nucleotides. As the extra sequence is located within a putative cytoplasmic loop that binds to G proteins, the two isoforms might interact with different G proteins and thereby initiate distinct intracellular signals.

705 citations


Journal ArticleDOI
TL;DR: Rats fed a diet low in alpha-linolenic acid showed an earlier mortality in response to an intraperitoneal injection of a neurotoxin, triethyltin, than did rats fed a normal soybean oil diet.
Abstract: Feeding rats diets containing oils that have a low alpha-linolenic acid [18:3(n-3)] content, such as sunflower oil, results in reduced amounts of docosahexaenoic acid [22:6(n-3)] in all brain cells and organelles compared to rats fed a diet containing soybean oil or rapeseed oil. During the period of cerebral development there is a linear relationship between the n-3 fatty acid content of the brain and that of food until alpha-linolenic acid represents approximately 200 mg/100 g food [0.4% of the total dietary energy for 18:3(n-3)]. Beyond that point brain levels reach a plateau. Similar values are also found for other organs. The level of 22:6(n-3) in membranes is little affected by the dietary quantity of linoleic acid [18:2(n-6)] if 18:3(n-3) represents approximately 0.4% of energy. In membranes from rats fed diets containing sunflower oil, Na+, K(+)-ATPase activity in nerve terminals was 60%, 5'-nucleotidase in whole brain homogenate was 80%, and 2',3'-cyclic nucleotide 3'-phosphodiesterase was 88% of that in membranes from rats fed diets containing soybean oil. A diet low in alpha-linolenic acid leads to anomalies in the electroretinogram, which partially disappear with age. It has little effect on motor activity, but it seriously affects learning tasks as measured with the shuttle box test. Rats fed a diet low in alpha-linolenic acid showed an earlier mortality in response to an intraperitoneal injection of a neurotoxin, triethyltin, than did rats fed a normal soybean oil diet.

660 citations


Journal ArticleDOI
TL;DR: The performance of subjects walking blindly to previously inspected visual targets (located at 5, 10 or 15 m from the subjects) was studied in 2 experiments and neural parameters encoded in the motor program for actually executing or mentally performing an action were discussed.

Journal ArticleDOI
TL;DR: Using in vitro amplification of cDNA by the polymerase chain reaction, this paper detected spliced transcripts of various tissue-specific genes (genes for anti-Mullerian hormone, beta-globin, aldolase A, and factor VIIIc) in human nonspecific cells, such as fibroblasts, hepatoma cells, and lymphoblasts.
Abstract: Using in vitro amplification of cDNA by the polymerase chain reaction, we have detected spliced transcripts of various tissue-specific genes (genes for anti-Mullerian hormone, beta-globin, aldolase A, and factor VIIIc) in human nonspecific cells, such as fibroblasts, hepatoma cells, and lymphoblasts. In rats, erythroid- and liver-type pyruvate kinase transcripts were also detected in brain, lung, and muscle. The abundance of these "illegitimate" transcripts is very low; yet, their existence and the possibility of amplifying them by the cDNA polymerase chain reaction provide a powerful tool to analyze pathological transcripts of any tissue-specific gene by using any accessible cell.

Journal ArticleDOI
TL;DR: New epidemiological evidence that hypertriglyceridaemia is an important predictor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes suggests a possible role of dyslipidaemia in the excessive occurrence of atherosclerotic vascular disease in this category of subjects.
Abstract: The Paris Prospective Study is a long-term investigation of the incidence of coronary heart disease in a large population of working men. The first follow-up examination involved 7,038 men, aged 43–54 years. Subjects with impaired glucose tolerance or diabetes (n=943) were selected from the total population for a separate analysis of coronary heart disease mortality risk factors. During a mean follow-up of 11 years, 26 of these 943 subjects with abnormal glucose tolerance died from coronary heart disease. Univariate analysis showed that plasma triglyceride level (p<0.006), plasma cholesterol level (p<0.02), and plasma insulin level both fasting and 2-h post-glucose load (p<0.02), were significantly higher in subjects who died from coronary heart disease compared to those who did not. In multivariate regression analysis using the Cox model, plasma triglyceride level was the only factor positively and significantly associated with coronary death. The distribution of plasma triglyceride levels was clearly higher for the subjects who died from coronary heart disease compared to those who did not die from this cause or were alive at the end of the follow-up. This new epidemiological evidence that hypertriglyceridaemia is an important predictor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes suggests a possible role of dyslipidaemia in the excessive occurrence of atherosclerotic vascular disease in this category of subjects.

Journal ArticleDOI
01 Jan 1989
TL;DR: In this article, the authors present a version francaise de l’echelle CES-D, instrument destine a etre employe en population generale, instrument deja valides dans la mesure clinique des etats depressifs.
Abstract: Cet article court presente la version francaise de l’echelle CES-D, instrument destine a etre employe en population generale. Les 20 items de l’echelle sont souvent presents chez les deprimes et sont issus d’instruments deja valides dans la mesure clinique des etats depressifs. L’evaluation repose sur l’etat au cours de la semaine precedente et les reponses sont du type jamais, tres rarement, a frequemment, tout le temps. Les etudes de validation de la version francaise ont ete realisees chez des malades psychiatriques hospitalises, chez des malades psychiatriques ambulatoires et en medecine generale. Les instruments auxquels le CES-D a ete compare comportaient la MADRS, les categories DSM III des troubles affectifs et un diagnostic ouvert de depression. La note seuil utilisee aux Etats-Unis ne parait pas etre pertinente en France. Les resultats suggerent une note seuil optimale de 17 pour les sujets masculins, 23 pour les sujets feminins. Nous soulignons qu’a l’heure actuelle ia valeur predictive de cet instrument pour un sujet individuel n’a pu encore etre evaluee.

Journal ArticleDOI
04 Aug 1989-Science
TL;DR: Hydropathy analysis suggests the existence of seven transmembrane domains that show homology with the corresponding regions of other G protein-coupled receptors.
Abstract: Complementary DNA clones, encoding the LH-hCG (luteinizing hormone-human choriogonadotropic hormone) receptor were isolated by screening a lambda gt11 library with monoclonal antibodies. The primary structure of the protein was deduced from the DNA sequence analysis; the protein contains 696 amino acids with a putative signal peptide of 27 amino acids. Hydropathy analysis suggests the existence of seven transmembrane domains that show homology with the corresponding regions of other G protein-coupled receptors. Three other types of clones corresponding to shorter proteins were observed, in which the putative transmembrane domain was absent. These probably arose through alternative splicing. RNA blot analysis showed similar patterns in testis and ovary with a major RNA of 4700 nucleotides and several minor species. The messenger RNA was expressed in COS-7 cells, yielding a protein that bound hCG with the same affinity as the testicular receptor.

Journal ArticleDOI
05 May 1989-Cell
TL;DR: Stimulation of transcription of reporter genes by the progesterone receptor was inhibited in transfected HeLa cells by co-expressing the estrogen receptor (ER) in an ER-dose- and estrogen-dependent manner, and it is proposed that these observations reflect competition for a functionally limiting transcription factor(s).

Journal ArticleDOI
TL;DR: The steady component of blood pressure is a strong risk factor for cardiovascular death in both sexes and the pulsatile component could be a risk factor independent of the steady component in women older than 55 years.
Abstract: Studies on the prognostic significance of blood pressure on cardiovascular disease have essentially investigated the levels of diastolic or systolic blood pressure. However, blood pressure may also be divided into two other components: steady (mean arterial pressure) and pulsatile (pulse arterial pressure). The relations of these two components with cardiovascular risk factors and cardiovascular mortality were investigated in 18,336 men and 9,351 women aged 40-69 years, who were followed up for a mean period of 9.5 years. However, the interpretation of the relations is complicated by the strong correlation existing between these two components. A principal component analysis was performed to obtain two independent parameters: a steady and a pulsatile component index, strongly correlated with mean and pulse arterial pressure, respectively. In the cross-sectional analysis, relations were stronger with the steady component index than with the pulsatile component index; an association was found between left ventricular hypertrophy and the pulsatile component index in both sexes. The survival analysis was not performed in women under 55 as only 11 cardiovascular deaths occurred in this group. The steady component index was a strong prognostic factor of all types of cardiovascular death in both sexes. In women, the pulsatile component index was positively correlated to death from coronary artery disease and inversely correlated to stroke. In conclusion, the steady component of blood pressure is a strong risk factor for cardiovascular death in both sexes; the pulsatile component could be a risk factor independent of the steady component in women older than 55 years.

Journal ArticleDOI
TL;DR: A randomized trial was conducted at the Institut Gustave-Roussy between 1972 and 1980 comparing tumorectomy and breast irradiation with modifiedradical mastectomy with modified radical mastectomy, with no significant differences between the two treatment groups.

Journal ArticleDOI
TL;DR: The M‐phase‐specific protein kinase from starfish oocytes at first meiotic metaphase is purified to near homogeneity using an improved procedure based on affinity chromatography on the immobilized yeast protein suc1, identical to MPF, the cytoplasmic factor that controls entry of eukaryotic cells into M‐ phase.
Abstract: We have purified to near homogeneity the M-phase-specific protein kinase from starfish oocytes at first meiotic metaphase, using an improved procedure based on affinity chromatography on the immobilized yeast protein suc1. As already reported, this is identical to MPF, the cytoplasmic factor that controls entry of eukaryotic cells into M-phase. MPF is a complex formed by the stoichiometric association of a 34-kd polypeptide previously identified as cdc2 with a polypeptide that migrates with the same mobility as starfish cyclin in SDS-PAGE (apparent mol. wt 47 kd). A cDNA clone encoding starfish cyclin B has been isolated and its sequence determined. It contains a single open reading frame encoding a predicted 43 729-dalton protein. Partial microsequencing of the 47-kd polypeptide component of MPF allowed its identification as the starfish cyclin. Since the apparent mol. wt of native starfish MPF was found to be less than 100 kd, it is a heterodimer comprising one molecule of cdc2 and one molecule of cyclin B.

Journal ArticleDOI
TL;DR: Experimental and clinical studies demonstrate that both laboratory and natural stressors alter the activities of lymphocytes and macrophages in a complex way that depends on the type of immune response, the physical and psychological characteristics of the stressor and the timing of stress relative to the induction and expression of the immune event.

Journal ArticleDOI
TL;DR: The more deeply located cells, of the dorsal and medioventral horns, had the most extensive rostrocaudal spread; they were found from L1 through the rostral sacral segments.
Abstract: This study used immunocytochemistry to examine the pattern of noxious-stimulus evoked expression of the proto-oncogene c-fos in the spinal cord of the rat. Both noxious somatic and joint stimulation in awake rats evoked the expression of c-fos protein in similar areas of the lumbar spinal cord. C-fos-immunoreactive neurons were found in laminae I and outer II, in the lateral part of the neck of the dorsal horn, and in laminae VII, VIII, and X. All of the labelled neurons were located ipsilateral to the injured hindpaw, except for lamina VIII where bilateral labelling was recorded. The c-fos-immunoreactive neurons in lamina I extended from the L3 segment to the rostral sacral cord; staining in outer lamina II was only found at the L4 segment. The more deeply located cells, of the dorsal and medioventral horns, had the most extensive rostrocaudal spread; they were found from L1 through the rostral sacral segments. The pattern of c-fos-immunoreactivity produced by visceral stimulation, in anesthetized rats, differed in several ways from that produced by somatic stimulation. First, there was considerable bilateral, symmetrical labelling of cells. Second, there was a much more extensive rostrocaudal spread of the labelling, from cervical through sacral cord. Third, the greatest rostrocaudal spread was found for neurons in the superficial dorsal horn; labelled cells in the neck of the dorsal horn and in lamina X were restricted to segments at the thoracolumbar junction, which is also where the superficial dorsal horn cells were most concentrated. Fourth, there were very few labelled neurons in the outer part of the substantia gelatinosa. To determine whether any neurons that express the c-fos protein in response to noxious stimulation project to supraspinal sites, we combined the immunocytochemical localization of c-fos with the localization of a retrogradely transported protein-gold complex that was injected into the thalamic and brainstem targets of the major ascending spinal pathways. In rats that received the somatic noxious stimulus, 90% of all of the c-fos projection neurons were recorded in four major areas of the cord: lamina I (37%), the lateral part of the neck of the dorsal horn (24%), laminae VIII (9%), and X (29%). The remainder were scattered throughout the spinal gray. With the exception of lamina VIII, which contained c-fos projection neurons contralateral to the inflamed paw, all of the c-fos projection neurons were located ipsilateral to the injured paw.(ABSTRACT TRUNCATED AT 400 WORDS)

Journal ArticleDOI
TL;DR: It is shown that the bacterially‐expressed product of the human rhoC gene is ADP‐ribosylated by C3 and corresponds in size, charge and behavior to the dominant C3 substrate of eukaryotic cells, suggesting that the unmodified form of a rho protein may be involved in cytoskeletal control.
Abstract: Clostridium botulinum C3 is a recently discovered exoenzyme that ADP-ribosylates a eukaryotic GTP-binding protein of the ras superfamily. We show now that the bacterially-expressed product of the human rhoC gene is ADP-ribosylated by C3 and corresponds in size, charge and behavior to the dominant C3 substrate of eukaryotic cells. C3 treatment of Vero cells results in the disappearance of microfilaments and in actinomorphic shape changes without any apparent direct effect upon actin. Thus the ADP-ribosylation of a rho protein seems to be responsible for microfilament disassembly and we infer that the unmodified form of a rho protein may be involved in cytoskeletal control.

Journal ArticleDOI
TL;DR: It is demonstrated that serum levels of IL-6, a potent myeloma cell growth factor in vitro, correlate with disease severity in plasma cell dyscrasias and anti-IL-6 or anti-il-6 receptor antibodies could be useful as therapeutic agents at this stage of the disease.
Abstract: Using a specific and very sensitive (1 pg = 1 U) bioassay, we investigated the presence of IL-6, a potent myeloma cell growth factor, in the sera of 131 subjects with plasma cell dyscrasias. 22 had monoclonal gammopathy of undetermined significance (MGUS), 13 had smoldering myeloma (SMM), 85 had overt multiple myeloma (MM), and 11 had plasma cell leukemia (PCL). Significant serum IL-6 levels were detected in only 3% of the MGUS/SMM group, but in 35% of the overt MM group and 100% of the PCL group. During overt MM, IL-6 was detected in 37% of the patients at diagnosis, 13% of those with stable MM, and 60% of those with fulminating disease. These data demonstrate that serum levels of IL-6, a potent myeloma cell growth factor in vitro, correlate with disease severity in plasma cell dyscrasias. Serial studies performed in 3 patients and correlative studies with labeling index in vivo in 25 patients have confirmed this concept. Taken together, this suggests that this cytokine is probably involved in vivo during the progressive phase of MM. Thus, anti-IL-6 or anti-IL-6 receptor antibodies could be useful as therapeutic agents at this stage of the disease.

Journal ArticleDOI
TL;DR: Results from this study suggested that one of the means of controlling resorbability (in vivo dissolution) of BCP ceramic is by varying its beta-TCP/HA ratio.
Abstract: Specially prepared biphasic calcium phosphate (BCP) macroporous ceramics consisting of an intimate association of beta tricalcium phosphate (beta-TCP) and hydroxyapatite (HA) with beta-TCP/HA weight ratios of 15/85, 35/65, and 85/15 were implanted in surgically created periodontal osseous defects in dogs and recovered after 6 months. A decrease in average size of crystals in BCP ceramics and an increase in the size of microporosities in the surface and at the core of the ceramic after implantation were observed, indicating that in vivo dissolution has taken place. The resorbability (reflecting in vivo dissolution) of BCP ceramics depended on their beta-TCP/HA ratios, the higher the ratio, the greater the resorbability. The formation of microcrystals with crystallographic properties and Ca/P ratio similar to those of bone apatite crystals were also observed. The abundance of these crystals were directly related to the beta-TCP/HA ratio of the BCP ceramic before implantation. The formation of the bone apatite-like crystals may be due to the precipitation of calcium and phosphate ions released from the dissolving ceramic crystals (the beta-TCP component dissolving preferentially to the HA component). Results from this study suggested that one of the means of controlling resorbability (in vivo dissolution) of BCP ceramic is by varying its beta-TCP/HA ratio.

Journal ArticleDOI
TL;DR: A method based on DNA amplification and hybridisation for the rapid detection of Mycobacterium tuberculosis was used to test 35 clinical specimens from 34 patients in whom tuberculosis was suspected.

Journal ArticleDOI
22 Sep 1989-Cell
TL;DR: Data suggest that a direct T cell receptor-MHC interaction occurs in the thymus in the absence of nominal antigen and results in the enhanced export of T cells, consistent with the concept of "positive selection".

Journal ArticleDOI
TL;DR: The first systematic account of the regional and laminar distributions of the catecholamine fibers in the human cerebral cortex is reported, using immunohistochemistry of thecatecholamines biosynthetic enzymes, tyrosine hydroxylase (TH), and dopamine‐β‐hydroxylases (DBH) in 13 cytoarchitectonic areas sampled postmortem.
Abstract: The organization of the cortical monoamine systems, dopamine (DA), and noradrenaline (NA), which have been studied extensively in the rat and more recently in the monkey, had not yet been investigated directly in the human brain. We report here the first systematic account of the regional and laminar distributions of the catecholamine fibers in the human cerebral cortex, using immunohistochemistry of the catecholamine biosynthetic enzymes, tyrosine hydroxylase (TH), and dopamine-beta-hydroxylase (DBH) in 13 cytoarchitectonic areas (4, 6, 9, 3b, 5, 40, 17, 18, 23, 24, 29, insula, and hippocampus) sampled postmortem. The noradrenergic (NA) innervation, mapped with DBH-immunoreactivity (DBH-IR), displayed a characteristic density gradient in the neocortex (highest in the primary sensorimotor areas, decreasing rostrally and caudally) that contrasted with the more uniform density in the limbic cortices (24, 23, 29, insula, hippocampus). NA axons were present in all cortical layers and were least numerous in layer I. The DBH-IR fibers were only partly TH-immunostained (10-50%, on double-labeled sections), suggesting a heterogeneity of the cortical NA axons. The putative dopaminergic (DA) fibers were identified by comparing alternate or double-immunolabeled (DBH-TH) sections, as the TH-IR fibers which contain no DBH-IR. A DA-like innervation was present in all cortical areas, with major regional differences in density and laminar distribution, which closely paralleled cytoarchitectural buildups: 1) the DA-like innervation was densest in the agranular areas, primary and secondary motor areas, anterior cingulate, and insula; it distributed throughout layers I-VI; 2) density was lower in the granular cortices, areas 9 (prefrontal cortex), 23, 3b, 5, 40, and 18, displaying a bilaminar pattern in layers I and V-VI. In all areas, DA-like fibers were most abundant in the molecular layer, with a predominant distribution in its deepest part. Convoluted and coily fibers represented a unique morphologic aspect of the CA innervation in the human cortex. These findings are in agreement with findings in nonhuman primates and demonstrate major evolutionary changes in the organization of the cortical aminergic input as compared with rodents. The most striking features are the expansion of the DA innervation to the whole cortex and the peak of highest density in the motor areas. The regional differentiation of NA innervation is also accentuated. Slight differences were found in the laminar distributions of the amines in humans and primates. These data seem quite promising and open new research fields in neurologic and psychiatric diseases.

Journal ArticleDOI
TL;DR: Compared of the seven human rab proteins with the yeast YPT1 (YPT1p) and SEC4 (SEC4p) proteins reveals highly significant sequence similarities and a possible involvement of the rab proteins in secretion is discussed.

Journal ArticleDOI
TL;DR: Peripheral T lymphocytes are tightly regulated by homeostatic mechanisms that control pool sizes and CD4/CD8 ratios, in a manner independent of the cell input into the peripheral compartment, which permits the maintenance at the periphery of any T cell specificity previously selected in the thymus.
Abstract: Peripheral T lymphocytes are self-renewable cell populations since, when transferred into syngeneic T cell-deficient athymic mice, they expand in the absence of exogenous antigen stimulation. Quantification of the expansion potential of CD4+ cells by transfer of the same population into successive host mice shows that these cells are able to divide up to 56 times in vivo. Therefore, as a population, CD4+ cells can increase in size 8 × 105-fold, an expansion potential of similar magnitude to that previously reported for colony-forming units. Injection of different numbers of T cells at different CD4/CD8 ratios is followed by T cell accumulation to a similar plateau in recipient nude mice. This indicates that peripheral T lymphocytes are tightly regulated by homeostatic mechanisms that control pool sizes and CD4/CD8 ratios, in a manner independent of the cell input into the peripheral compartment. This kinetic behavior of mature T cells permits the maintenance at the periphery of any T cell specificity previously selected in the thymus. The expansion capacity of peripheral T cells may also allow extensive modulation of peripheral T cell specificities, which would confer a major role to post-thymic selection of mature peripheral T cell repertoires.

Journal ArticleDOI
21 Apr 1989-Cell
TL;DR: It is proposed that initiation of M phase is brought about by the dephosphorylation of p34cdc2, leading to increase in its protein kinase activity.