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Biomedical subjects

P Lebon

Publications and source records attributed to P Lebon.

At least 109 records · Page 6Linked to original sources
PubMed1991

Analysis of retroviral sequences in the spinal form of multiple sclerosis.

The polymerase chain reaction was used, in a blind study, to look for retroviral sequences in DNA extracted from the peripheral blood mononuclear cells of 11 patients with the spinal form of multiple sclerosis (MS). Control subjects consisted of 7 patients with other neurological diseases and 5 healthy blood donors. Three sets of oligonucleotides were used. They could detect all known human oncoretroviruses, lentiviruses, or spumaretroviruses. The primers recognized conserved sequences in the long terminal repeats of the proviral DNA. Control experiments showed that the primers crossreacted within the human immunodeficiency virus or human T-cell lymphotropic virus group and that they provided the expected level of sensitivity. Therefore the assay could have detected not only known human retroviruses but also new related members. In spite of this, no retroviral sequences were detected in either the MS or the control specimen.

Adult↗
PubMed1991

Intrathecal synthesis of IgG subclasses in multiple sclerosis and in acquired immunodeficiency syndrome (AIDS).

Serum and cerebrospinal fluid (CSF) of 50 neurological patients (24 multiple sclerosis (MS), ten acquired immunodeficiency syndrome (AIDS) and 16 other neurological diseases (OND)) and ten controls were analyzed by enzyme-linked immunosorbent assay (ELISA) for IgG subclass quantification and for the calculation of intrathecal synthesis (ITS). Total IgG was determined by two methods: electroimmunodiffusion (EID) and ELISA. A highly significant correlation was established between both methods. The existence of ITS was proved by the IgG/albumin ratio, the IgG index, Tourtellotte's formula, and Schuller's formula. In AIDS patients all IgG subclasses showed an increase in the CSF, whereas in sera only the IgG1 was significantly increased. CSF of MS patients showed a predominant increase of IgG1 whereas no significant modification of IgG subclasses was observed in sera. In most of the AIDS patients there was an ITS of IgG1, IgG3 and IgG4, but rarely (3/10) IgG2. In contrast, a polyclonal ITS of IgG was exceptional (1/24) in MS patients. No significant correlation could be established between clinical data and IgG subclass ITS in MS. The variations of each IgG subclass in serum and in ITS were not significantly correlated. Measurement of each IgG subclass and calculation of ITS seems essential in order to analyze any subclass antibody repertory inside the central nervous system.

Acquired Immunodeficiency Syndrome↗
PubMed1991

A phase I trial of 21-day continuous venous infusion of alpha-interferon at circadian rhythm modulated rate in cancer patients.

The toxicity and/or the stimulation of natural killer cell activity that resulted from exposure to alpha-interferon varied according to circadian dosing time, both in mice and in human beings. Ten patients with advanced renal cell carcinoma or melanoma were treated with recombinant alpha-interferon-2b using a continuous 21-day intravenous schedule at circadian modulated rate. Patients received 15-20 MU/m2/day in an ambulatory care program. The drug was delivered via an external programmable-in-time pump. Thirty-nine courses of therapy were given (2-12 courses per patient). Severe side effects included World Health Organization grade III somnolence (one patient, 1 course) and grade III-IV neutropenia (five patients, 10 courses). Karnofsky performance status decreased by 40% in 3 patients (five courses). Two of these patients were withdrawn from the study because of toxicity. Disease was stabilized in four of the seven patients evaluable for response. Seven of the 10 patients are alive at 15 months' median follow-up. Two have continued with chronotherapy for 9+ and 13+ months, respectively. A large interpatient variability characterized the maximally tolerated dose. Two patients led their usual activities while receiving 20 MU/m2/day for three courses or more. Conversely, two patients exhibited severe side effects with 10 MU/m2/day. As compared with schedules of standard administration or continuous flat infusion, this circadian schedule of infusion allowed a large increment in total daily dose and dose intensity. A starting dose of 15 MU/m2/day was well tolerated by 8 of 10 patients and can be recommended using this circadian modulated schedule.

Adult↗
PubMed1991

Amplification and characterization of herpesvirus DNA in cerebrospinal fluid from patients with acute encephalitis.

A single pair of oligonucleotide primers selected within a highly conserved region of the DNA polymerase gene of the herpesviruses was designed to amplify related viral genomes, i.e., herpes simplex virus type 1, herpes simplex virus type 2, Epstein-Barr virus, and cytomegalovirus, by the polymerase chain reaction. A simple restriction enzyme analysis of these amplified products allowed accurate characterization of the herpesvirus type. Ninety-nine cerebrospinal fluid samples from 36 patients (including newborns, children, and adults) with acute encephalitis were tested for the presence and identification of herpesvirus DNA by this approach. High levels of viral DNA, which were readily visualized by simple ethidium bromide staining, were found in all these patients from the first days of the disease and, in some cases, until the third week following the onset of acute encephalitis. The herpesvirus type was rapidly identified by enzymatic digestion in 33 patients' samples and by hybridization and direct sequencing in the last 3 patients' samples. Our results show that the polymerase chain reaction provides a highly sensitive and specific technique for the identification of herpesviruses DNA in cerebrospinal fluid that should be of value for early and rapid diagnosis, therapeutic decisions, prognostic evaluation, and epidemiological studies.

Acute Disease↗
PubMed1991

[Viral infection in the neonatal period: diagnostic difficulties, the role of interferon alpha levels].

Serum and/or cerebrospinal fluid (CSF) alpha interferon (aIFN) levels were determined in 31 neonates hospitalized for suspected sepsis. Final diagnosis was bacterial sepsis in 15, viral infection in 13 and no infection in 3. Among the 13 neonates with viral infection, enterovirus was isolated 5 times and coxsackievirus 4 times. No aIFN was found in cerebro-spinal fluid and/or serum among the neonates with bacterial sepsis or without infection. By contrast, in neonates with viral infection, CSF and/or serum aIFN levels were always elevated except in one case in which serum aIFN determination was not available. We conclude that in neonates, elevated levels of CSF and serum aIFN appear to be specific of viral infection, and that this might be helpful in the differential diagnosis of suspected sepsis.

Coxsackievirus Infections↗
PubMed1990

Presence of gamma interferon in human acute and congenital toxoplasmosis.

The production of gamma interferon in acute acquired and congenital toxoplasmosis was studied. Gamma interferon was produced at significant titers (P less than 0.001) in the course of both congenital toxoplasmosis and acquired toxoplasmosis at an early stage of infection, when Toxoplasma gondii was multiplying. Its presence in fetal blood was correlated with the positive inoculation of fetal blood or amniotic fluid into mice (95%). The data suggest that the fetus is able to synthesize gamma interferon as early as week 21 of pregnancy. This test, easily and rapidly performed, could be included among those useful for diagnosing fetal toxoplasmic disease.

Acute Disease↗
PubMed1990

[Delayed acute measles encephalitis].

Delayed acute encephalitis is a rare complication of measles that may occur either in immunodepressed patients or in patients without overt immunodepression. In the present series of 8 cases, diagnosis was made on CSF/serum measles antibody titre and/or intranuclear paramyxovirus nucleocapsides identified by electron microscopy in the central nervous system cells. The disease is characterized by the association of focal defects (monoparesis, hemiparesis, aphasia, a.s.o.) with periodic myoclonic jerks without major impairment of consciousness. The encephalitis lasted 2 to 4 weeks and 3 patients died. With the exception of 1 case, all the patients had severe sequelae after a follow-up of 1 to 9 years. The EEG showed diffuse polymorphous delta waves, with a predominance on the side opposite to the myoclonias and pseudoperiodic complexes in all cases. CT scan was abnormal in 4 of 6 cases, showing hypodense areas. Antiviral or immunogenic therapeutic trials were administered to 5 patients without clear improvement. Sensitive methods of antibody dosage seem to be useful for the early diagnosis of the disease.

Acute Disease↗
PubMed1989

Synergistic cytotoxic effects of recombinant human tumor necrosis factor, interferons, and heat-stress.

A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (TNF-alpha), interferons (IFN-alpha, IFN-beta, and IFN-gamma) and heat-stress was demonstrated in vitro. The toxicity of these agents was assessed in the human cervical carcinoma HeLa cell line: the toxic effect was greatly increased when cells pretreated with IFNs or TNF were submitted to a 1-h heat-shock at 45 degrees C. Moreover if the heat-stress followed simultaneous treatment with both cytokines, a synergistic effect between these treatments could be observed. The same observations were made for two other transformed cell lines: the oral epidermoid carcinoma KB cells and the hepatocarcinoma PLC/PRF/5 cells. In contrast, the survival of normal cells (normal foetal lung MRC5 cells and foreskin F 7000 fibroblasts) was only slightly decreased by such treatments. These results suggest that combining a heat-stress with cytokines treatment might be one way of enhancing the sensitivity of cancer cells to the growth inhibitory effects of the individual cytokines.

Cell Division↗
PubMed1989

Reduced activity of the interferon-induced double-stranded RNA-dependent protein kinase during a heat shock stress.

Previous studies have shown that the antiviral response induced by interferon in murine cells could be degraded after a heat shock. Here we have confirmed that a similar effect occurs also in interferon-treated human HeLa cells subjected to a heat shock. In addition, we have investigated the fate of the interferon-induced, double-stranded RNA-dependent protein kinase in heat-shocked cells. This protein kinase is a Mr 68,000 protein (p68 kinase) which, when autophosphorylated, catalyzes phosphorylation of the protein synthesis eukaryotic initiation factor-2, thus mediating inhibition of protein synthesis. After heat shock of interferon-treated HeLa cells, the double-stranded RNA-dependent autophosphorylation of p68 kinase in cytoplasmic extracts is greatly reduced whereas the phosphorylation of other cellular proteins is not affected. In vivo, autophosphorylation of p68 kinase is also reduced in heat-shocked cells whereas there is no apparent effect on the phosphorylation state of other proteins. In such cells, the interferon-mediated antiviral response becomes modified according to the virus challenge, i.e. these cells remain resistant to vesicular stomatitis virus but become partially sensitive to encephalomyocarditis virus (EMCV) infection. The reduction in the activity of p68 kinase is due to its reduced nonionic detergent solubility occurring during the heat shock period. The resultant reduced detergent extractibility of p68 kinase is dependent on the intensity of the thermal stress. In contrast to the effect after a heat shock, arsenite treatment of interferon-treated HeLa cells induces heat shock proteins, but neither modifies the antiviral response nor affects the extractibility of p68 kinase. These results indicate that the degradation of the anti-EMCV response and reduced p68 kinase activity occur in response to heat treatment independently of the induction of heat shock proteins. The role of p68 kinase in the mechanism of the antiviral response against EMCV and vesicular stomatitis virus is discussed.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

Immunoglobulins and complement components in 37 patients infected by HIV-1 virus: comparison of general (systemic) and intrathecal immunity.

Intrathecal (IT) immunity was assessed by simultaneous analysis of paired cerebrospinal fluid (CSF) and sera of 37 patients infected by human immunodeficiency virus-1 (HIV-1). Only 8 of these 37 patients had no neurological or neuropsychiatric symptoms. There were 3 prominent abnormalities observed: (1) IT IgA production occurred in 15 patients, IT IgM production in 14 patients, and IT IgG production in 34 patients. (2) IT Anti-HIV-1 antibody specific activity (ASA) was higher than in serum in 33 of the 37 patients indicating that IT synthesis of antibody specific for HIV-1 occurs even in asymptomatic patients; IT anti-HIV-1 antibody synthesis was not correlated with clinical severity or neurological involvement. IT anti-herpes simplex ASA was also higher than serum ASA in 6 patients indicating a possible associated herpes simplex virus infection. (3) IT production of the complement component C4 was found frequently and was highly correlated with increased serum C4. IT C3 levels were decreased in 21 of 37 patients indicating that complement activation is a frequent accompaniment of the IT immune response in HIV-1-positive patients. These results indicate a unique and localized IT immune response which is different from the pattern observed in the systemic immune compartment in HIV-1-seropositive individuals and from the pattern common to the other CNS infectious diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Encephalopathy with calcifications of the basal ganglia in children. A reappraisal of Fahr's syndrome with respect to 14 new cases.

Calcifications of the basal ganglia are described under the heading of "Fahr's syndrome". The clinical pattern is variable and the syndrome may be sporadic or familial. This study describes a personal series of 14 cases of encephalopathy with calcification of the basal ganglia and reviews the literature cases. A four-group classification is proposed. The first group includes encephalopathy, microcephaly, dwarfism, retinal degeneration or optic atrophy, symmetrical patchy demyelination with calcifications and probable autosomal recessive inheritance. Some cases have an early onset, a rapid evolution. Others have a later onset, longer course and retinal degeneration. In the second group, the children suffer from a congenital encephalopathy or a cerebral palsy without clear deterioration, without short stature, ocular impairment or persistent CSF abnormalities. This group has not been reported in the literature. The cases do not seem to be genetic. The precise cause in unknown but a sporadic non progressive anoxo-ischemic, or viral prenatal disease is suggested. In the third group, the association of encephalopathy, microcephaly, and persistent CSF lymphocytosis, has a high recurrence rate. The pathogenesis is still a matter of dispute. The fourth group is characterized by autosomal dominant calcifications of the basal ganglia with or without neurological abnormalities. Finally calcium metabolism disorders and mitochondrial encephalomyopathy may be associated with calcifications of the basal ganglia.

Basal Ganglia Diseases↗
PubMed1989

Immunohistochemical analysis of brain macrophages in adrenoleukodystrophy.

Using a panel of monoclonal antibodies directed against antigenic determinants present at the surface of mononuclear cells, we characterized the macrophage infiltration in frozen brain specimens from a patient with adrenoleukodystrophy by immunohistochemical staining. This study demonstrated that macrophages were the main infiltrating cells in the white matter and that there was a wide variability in their phenotype according to their location: they stained very strongly with Leu-M5, EBM11, Leu-M3, To5 and 2LPM 19 C in the perivascular cuffs, whereas they stained principally with Leu-M5 and EBM11 and to a lesser extent with To5 and 2LPM19c in the white matter. In addition to the expression of MHC class II and CD4 molecules, macrophages exhibited strong labelling with 7G7B6, a monoclonal antibody raised against IL2 receptors. These results attest that macrophages, which infiltrate the brain parenchyma have various phenotypes, and very likely different states of activation, and suggest that interleukin-2 plays an important role during this activation.

Adrenoleukodystrophy↗
PubMed1988

Interferon gamma in acute and subacute encephalitis.

Intrathecal synthesis of interferon gamma was shown in 14 out of 16 samples of cerebrospinal fluid collected in the first days of disease in adults, children, and newborn infants with herpes encephalitis. This synthesis was concomitant with that of interferon alpha and was switched off when the specific antibodies in the central nervous system increased. No endogenous interferon gamma was detected in 11 serum samples or 13 samples of cerebrospinal fluid collected early in the course of the disease from patients with measles encephalitis and rubella encephalitis, or in serum and cerebrospinal fluid samples from seven patients with subacute sclerosing panencephalitis. In serum collected after the 10th day after the onset of neurological symptoms interferon gamma was present at low concentrations in only three out of 11 serum specimens from patients with measles encephalitis or rubella encephalitis. Interferon gamma was present in patients with acute herpes encephalitis and there was active virus replication, but it was not present in postinfectious encephalitis. Possibly the local production of specific antibodies masks the viral antigens and switches off the induction of interferons.

Acute Disease↗
PubMed1988

Multiple sclerosis: involvement of interferons in lesion pathogenesis.

To investigate a possible role of interferons (IFNs) in lesion pathogenesis, central nervous system tissue from multiple sclerosis patients and control subjects was stained by immunocytochemical techniques in combination with monoclonal antibodies or polyclonal antisera for the demonstration of IFN-alpha, IFN-beta, and IFN-gamma. The results were correlated to lesion activity, to the presence of class I and class II major histocompatibility antigen-positive astrocytes, and to the composition of cellular infiltrates. IFNs were detectable in active but not in inactive chronic multiple sclerosis lesions. In acute multiple sclerosis plaques, all three types of IFN were widely distributed on glial elements and infiltrating cells. In active chronic multiple sclerosis, labeling of cells for IFN-alpha, IFN-beta, and IFN-gamma was most pronounced at the lesion edge and displayed distinct distribution patterns. Overall, IFN-gamma was more common than IFN-alpha and IFN-beta and was predominantly found on astrocytes. IFN-alpha was detectable mainly on macrophages. Distribution of IFN-beta partially overlapped with that of IFN-gamma and IFN-alpha, in that it was present on some astrocytes and on some macrophages. IFNs were rare in normal white matter remote from lesions and in the gliotic lesion center. Ia antigen and human leukocyte antigen ABC on astrocytes were distributed similarly to IFN-gamma and IFN-beta, respectively. These findings indicate that IFN-gamma may play a role in active lesion growth in multiple sclerosis, whereas IFN-alpha and IFN-beta may exert some local immunosuppressive effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Regulation of the heat-shock response by interferon in mouse L cells.

Interferon (IFN) is not able to induce heat-shock protein (HSP) synthesis. However IFN pretreatment of mouse L cells has been shown to enhance the decrease of overall protein synthesis which follows a heat shock, and to stimulate the accumulation of HSPs. We show here that the synthesis of a protein (the hepatitis B virus surface antigen) under the control of a Drosophila HSP 70 promoter is also stimulated in IFN-pretreated cells. The regulation by IFN takes place at two levels: first, the rate of HSP gene transcription is increased in nuclei isolated from IFN-treated cells; second, the synthesis of HSPs is prolonged after pretreatment with IFN. Experiments performed in the presence of actinomycin D show that this effect is due to a stabilization by IFN of mRNAs coding for HSPs.

Animals↗
PubMed1988

Intrathecal synthesis of interferon-alpha in infants with progressive familial encephalopathy.

IFN-alpha was detected in cerebrospinal fluid and/or sera from 7 of 8 patients with a progressive familial encephalopathy associated with calcifications of the basal ganglia and white matter alterations. The secretion of IFN-alpha was prolonged, as shown by its presence at different times between birth and 5 years, and was not associated with IFN-gamma. Virological investigations excluded various congenital infections. In only 2 patients, high levels of Epstein-Barr virus antibodies were observed, indicating the possibility of an abnormal response to viral infection rather than a congenital infection. Further investigations are required for characterization of the recessive autosomal trait of this syndrome and its relation to the IFN system.

Antibodies, Viral↗