Search PubMed⌕ Search

Biomedical subjects

M Ceroni

Publications and source records attributed to M Ceroni.

At least 55 records · Page 3Linked to original sources
PubMed1990

Molecular mass, biochemical composition, and physicochemical behavior of the infectious form of the scrapie precursor protein monomer.

A highly purified fraction obtained from scrapie (263-K strain)-infected hamsters' brains by an alternative procedure without proteinase K treatment contained a protease-resistant form of the scrapie precursor protein (PrPSc) and infectivity of 9.9 +/- 0.7 log LD50/ml. Polyclonal antibodies produced against hamster scrapie amyloid protein (PrP27-30) and used in a neutralization test diminished infectivity of the PrPSc preparations by 1.6 log after intracerebral inoculation and by 1 log after intraperitoneal inoculation. PrPSc was subjected to size-exclusion HPLC; greater than or equal to 60% of the eluted infectious units were recovered from the peak with an apparent mass of 30.4 +/- 0.6 kDa. Characterization by UV absorption spectra, SDS/PAGE, immunoblots, N-terminal amino acid sequence, and neutral sugar and amino sugar analyses demonstrated homogeneity of the infectious units. The neutral sugar and amino sugar compositional analyses revealed high mannose, glucosamine, fucose, and sialic acid content. This demonstrated an extensive posttranslational modification by the complex type of N-linked glycosylation and glycane core of C-terminal glycolipid of PrPSc. The results correspond to the predicted size, composition, and sequence of PrPSc and indicate that this protein may be the only component of scrapie infectious unit or the infectious form of scrapie precursor.

Amino Acid Sequence↗
PubMed1990

Subcellular distribution and physicochemical properties of scrapie-associated precursor protein and relationship with scrapie agent.

We studied the biologic properties of hamster-adapted scrapie (strain 263K) and its relationship to the precursor protein of scrapie (PrP33-35Sc). The highest titer of infectious material and the greatest concentration of PrP33-35Sc were in the fractions containing microsomal and synaptosomal membranes. We found traces of infectivity in the absence of PrP33-35Sc associated with matrix protein. Partitioning of membranes with neutral chloroform-methanol resulted in concentration of PrP33-35Sc and infectivity within the interphase layer. Recombination of membrane glycoproteins (interphase) with lipids extracted from homologous brains decreased infectivity greater than or equal to 4 logs. Temperature-dependent phase separation of infected synaptosomal and microsomal membranes with Triton X-114 yielded a phospholipid-rich phase containing a high concentration of PrP33-35Sc and greatest infectivity titers. This material spontaneously formed liposomes, indicating that PrP33-35Sc and PrP33-35C precursor proteins are highly hydrophobic intrinsic membrane components integrated with phospholipids. Homologous membrane phospholipids appear to prevent aggregation of the scrapie isoform of PrP and maintain high levels of infectivity.

Animals↗
PubMed1990

Scrapie infectivity and prion protein are distributed in the same pH range in agarose isoelectric focusing.

We separated lysed synaptosomal-microsomal membrane fraction from scrapie-infected hamster brain in preparative agarose isoelectric focusing. We also studied the distribution of PrP27-30 and scrapie infectivity in 13 regions of the gel in the range of pH 3.5 to 9.3. Most of the infectivity remained in the trough, where it had been placed at the beginning of the electrophoresis, along with PrP27-30. Scrapie infectious particles that encountered the gel demonstrated charge heterogeneity and were distributed in the range of pH 5.4 to 9.3. Analysis of charge heterogeneity of PrP27-30 after sodium dodecyl sulfate solubilization showed an isoelectric pattern in the same pH range as that for scrapie infectious particles. The similarity in charge heterogeneity between infectivity and PrP27-30, together with copurification, support the idea that PrP27-30 is an essential component of the scrapie infectious agent.

Animals↗
PubMed1990

Scrapie-associated precursor proteins: antigenic relationship between species and immunocytochemical localization in normal, scrapie, and Creutzfeldt-Jakob disease brains.

We describe the antigenic properties and detection of a normal isoform of scrapie-associated precursor protein (PrP33-35C) in normal, and both normal and scrapie isoforms in scrapie- or Creutzfeldt-Jakob disease (CJD)-infected mouse, hamster, and human brains, using a variety of specific antibodies. Polyclonal antibodies raised against mouse and hamster PrP27-30 and against a synthetic peptide of the N-terminal sequence of this protein were used as immunologic probes. PrP27-30 purified as a primary immunogen corresponded to the lower molecular mass peptide, with Mr between 9.3 and 13.5 kd as estimated by size-exclusion high-pressure liquid chromatography. ELISA and immunoblot techniques demonstrated that antibodies recognized homologous antigens as well as precursor proteins from brains (PrP33-35C) and the scrapie isoform of scrapie-associated proteins (PrP33-35Sc/CJD and PrP27-30) from scrapie- and CJD-infected brains. The normal, scrapie, and CJD isoforms of scrapie-associated proteins share common epitopes with varying degrees of interspecies homology. Specific antigen detected in neurons indicated that these proteins are synthesized primarily in these cells. In infected brains, extracellular amyloid deposits formed by the scrapie isoform of PrP protein also strongly reacted with anti-PrP antibodies.

Animals↗
PubMed1990

Immunohistochemical localization of prion protein in spongiform encephalopathies and normal brain tissue.

We used polyclonal antibodies raised against hamster and mouse PrP27-30 as immunologic probes to study the localization of intracellular and extracellular deposits of prion protein in normal and scrapie-infected mouse and hamster brains and in Creutzfeldt-Jakob disease (CJD)-infected mouse brains. In addition, we examined normal human brain and brain tissues from patients with CJD, kuru, Alzheimer's disease, and idiopathic chronic encephalitis. There was positive staining in the cytoplasm of neurons of normal and scrapie- and CJD-infected mice, and in the neurons of normal and scrapie-infected hamsters. The staining pattern suggests the localization of PrP in an intracellular membrane compartment, most likely the rough endoplasmic reticulum or Golgi apparatus. Antibodies raised against a 15-amino-acid synthetic peptide of the N-terminal of hamster PrP27-30 displayed a similar pattern of staining in mouse brain sections. We observed no intracellular staining in human brain sections obtained at autopsy. Antibodies prepared against mouse and hamster PrP27-30 reacted with amyloid plaques in scrapie-infected mouse and kuru- and CJD-infected human brain sections but not with amyloid plaques in the brain of a patient with Alzheimer's disease.

Alzheimer Disease↗
PubMed1990

Serum and cerebrospinal fluid herpes simplex virus type 1 immunoglobulin G and M titers in four cases of herpes simplex encephalitis.

Herpes simplex virus type 1 (HSV-1) IgG and IgM ELISA titers were serially determined in serum and cerebrospinal fluid (CSF) samples from 4 patients with HSV-1 encephalitis during a follow-up period of 1-26 months. In 3 out of 4 patients HSV-1 IgM titers raised in CSF during the acute phase of disease, thus allowing differentiation between primary and reactivated forms of HSV-1 encephalitis. HSV-1 IgG titers showed a sharp elevation earlier in serum than in CSF. Specific IgG index documented a large intrathecal production of HSV-1 IgG and their persistence 2 years following clinical onset. The initial trend of serum and CSF specific IgG titer represents a reliable tool for a retrospective diagnosis of HSV-1 encephalitis.

Antibodies, Viral↗
PubMed1990

Specific activation of B-cell clones within the central nervous system in course of herpes simplex encephalitis.

Total and virus-specific immunoglobulin (Ig) G oligoclonal bands were studied in paired serum and cerebrospinal fluid (CSF) of four patients with herpes simplex virus type 1 (HSV-1) encephalitis. We used the isoelectric focusing in agarose gel, a sensitive technique for protein separation, followed by passive transfer of proteins on nitrocellulose paper and specific immunostaining. Oligoclonal bands were observed in serum and CSF of all patients. HSV-1-specific oligoclonal IgG bands were present in the CSF only during a limited period of the disease, having their counterpart in serum during the remaining periods. Our findings contribute to tackle the issue of B-cell activation within central nervous system and peripheral blood compartments in course of HSV-1 encephalitis.

Antibodies, Viral↗
PubMed1989

Transient intrathecal IgG synthesis in herpes zoster myelitis: 2 case reports.

Alterations in cerebrospinal fluid in 2 cases of viral myelopathy associated with herpes zoster infection are reported. Viral myelopathy is a rare complication of herpes zoster. Quantitatively there was a slight increase in IgG production and oligoclonal IgG bands were detected by isoelectric focusing. These parameters returned to normal after 1 year suggesting a transient involvement of the central nervous system.

Adult↗
PubMed1988

The role of HTLV-I in tropical spastic paraparesis in Jamaica.

We report clinical and laboratory investigations of 47 native-born Jamaican patients with endemic tropical spastic paraparesis and of 1 patient with tropical ataxic neuropathy. Mean age at onset was 40 years, with a female-male preponderance (2.7:1). Neurological features of endemic tropical spastic paraparesis are predominantly those of a spastic paraparesis with variable degrees of proprioceptive and/or superficial sensory impairment. Using enzyme-linked immunoabsorbent assay (ELISA), IgG antibodies to human T-lymphotropic virus type I (HTLV-I) were present in 82% of sera and 77% of cerebrospinal fluids. On Western blot analysis, IgG antibodies detected the p19 and p24 gag-encoded core proteins in both serum and cerebrospinal fluid. Titers were tenfold higher by ELISA in serum than in cerebrospinal fluid, and some oligoclonal bands present in fluid were not seen in serum. Serum-cerebrospinal fluid albumin ratios were normal, and IgG indexes indicated intrathecal IgG synthesis. Histopathological changes showed a chronic inflammatory reaction with mononuclear cell infiltration, perivascular cuffing, and demyelination that was predominant in the lateral columns. In 1 patient, a retrovirus morphologically similar to HTLV-I on electron microscopy was isolated from spinal fluid. Our investigations show that endemic tropical spastic paraparesis in Jamaica is a retrovirus-associated myelopathy and that HTLV-I or an antigenically similar retrovirus is the causal agent.

Adolescent↗
PubMed1988

Tropical spastic paraparesis: clinical, immunological, and virological studies in two patients from Martinique.

Two patients from Martinique with tropical spastic paraparesis had antibodies to human T-lymphotropic virus type I (HTLV-I) in serum and spinal fluid but no antibodies to other retroviruses tested. They presented with spastic weakness of both lower extremities, hyperreflexia with upgoing toes, sphincteric dysfunction, and normal sensation. By means of agarose isoelectric focusing and selective immunoblotting we demonstrated an increased intrathecal synthesis of IgG antibodies to HTLV-I in the spinal fluid. Unique oligoclonal bands of IgG antibodies to HTLV-I were present in the cerebrospinal fluid. Using a battery of monoclonal antibodies we also found in these patients an increased number of circulating T cells that expressed activation markers. We conclude that the HTLV-I retrovirus associated with tropical spastic paraparesis has both lymphocytotropic and neurotropic properties.

Adult↗
PubMed1988

Intrathecal synthesis of IgG antibodies to HTLV-I supports an etiological role for HTLV-I in tropical spastic paraparesis.

High titers of antibody to human T-lymphotropic virus type I (HTLV-I) have been reported in the sera and cerebrospinal fluids of patients with tropical spastic paraparesis. By means of agarose isoelectric focusing and selective immunoblotting, we demonstrated oligoclonal bands of immunoglobulin G antibodies to HTLV-I in the serum and cerebrospinal fluid of patients with tropical spastic paraparesis. Such cerebrospinal fluid-specific immunoglobulin bands indicate intrathecal synthesis of specific antibodies to HTLV-I. These findings mimic the antibody response to measles virus in subacute sclerosing panencephalitis and support an etiological role for HTLV-I in the pathogenesis of tropical spastic paraparesis.

Antibodies, Anti-Idiotypic↗
PubMed1988

Seroprevalence of antibodies to HTLV-I in patients with chronic neurological disorders other than tropical spastic paraparesis.

Human T-lymphotropic virus type I (HTLV-I), the etiological agent of adult T-cell leukemia/lymphoma, also appears to be the cause of tropical spastic paraparesis, a chronic myelopathy reported in several different regions of the world. The prevalence of antibodies to HTLV-I in patients with chronic neurodegenerative disorders other than tropical spastic paraparesis and in patients with some muscle inflammatory disorders has been investigated. IgG antibodies to HTLV-I were measured in the sera and/or cerebrospinal fluid from 82 Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia, 164 Guamanian normal controls, 10 patients with kuru from the Eastern Highlands of Papua New Guinea, 4 patients with Viliuisk encephalomyelitis from the Iakut region of eastern Siberia, 45 Italian patients with multiple sclerosis, and 56 patients with polymyositis (49 from the United States and 7 from Jamaica). As determined by enzyme-linked immunosorbent assay, Western immunoblot, and gelatin particle agglutination techniques, serological evidence of HTLV-I infection was found in 1 patient with amyotrophic lateral sclerosis and 1 control subject from Guam, and in 1 patient from the United States and all 7 Jamaican patients with polymyositis. Except for the high seropositivity rate among the group of Jamaican patients with polymyositis, our data indicate that HTLV-I is an unlikely causative agent in the spectrum of the neurological diseases examined. The seropositivity of the 7 Jamaican patients with polymyositis requires further study.

Adult↗
PubMed1988

Detection of HTLV-III-specific IgG bands in the CSF from a patient with AIDS and encephalitis.

Recent evidence would suggest that HTLV-III may be neurotropic. We have found oligoclonal IgG bands by isoelectric focusing in the CSF of a homosexual man with AIDS and encephalitis. Subsequent analysis revealed that such bands contained anti-HTLV-III activity, suggesting that neurologic symptoms in AIDS patients may be caused by replication of HTLV-III inside the CNS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Identification of HIV-specific oligoclonal immunoglobulins in serum of carriers of HIV antibody.

Zone electrophoresis on agarose gel was performed on serum samples from HIV-antibody carriers and negative controls. Nitrocellulose strips precoated with an HIV preparation were then placed on top of the gels and developed by an immunoblotting procedure. A positive reaction was demonstrated between the HIV antigens and the HIV-antibody-positive serum samples with hypergammaglobulinemia and oligoclonal IgG bands. A negative reaction was found between the HIV antigens and HIV-antibody-negative serum samples from a normal person and a patient with monoclonal gammopathy. The presence of oligoclonal IgG bands in the serum of HIV-antibody carriers, and their positive identification with HIV antigens, indicates a specific immune response of the host to the HIV infection and supports the use of oligoclonal IgG bands as markers to follow the course of HIV infection.

Antibodies, Viral↗
PubMed1988

Acute experimental allergic encephalitis. Treatment with fungal polysaccharides.

This report describes the effects of a fungal polysaccharide mixture on the Experimental Allergic Encephalitis (EAE) in guinea pigs. The clinical, histopathological and IgG intrathecal synthesis related studies in the EAE sensitized group was compared with that observed in EAE sensitized groups treated with fungal polysaccharides. The results indicate that the fungal polysaccharide mixture is capable of inducing a more localized and milder inflammatory reaction in the guinea pig with EAE. We hypothesize that the fungal polysaccharides can activate complement by the alternative pathway, subtracting it to the specific immune response to EAE.

Animals↗