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Biomedical subjects

C J Gibbs

Publications and source records attributed to C J Gibbs.

At least 91 records · Page 5Linked to original sources
PubMed1991

Neutralizing antibody responses in patients with AIDS with neurologic complications.

Although the human immunodeficiency virus type 1 (HIV-1) is frequently isolated from the cerebrospinal fluid of infected patients, only a small percentage of patients are found to have clinical dementia or neuropathies (or both). The reasons for this remain unclear. In our study, serum neutralizing antibody titers against the human T cell leukemia virus-IIIB isolate of HIV-1 were tested in 10 patients with acquired immunodeficiency syndrome (AIDS) with neurologic complications and 20 patients with HIV infection without neurologic complications. Titers were significantly lower in the neuro-AIDS group, suggesting that impaired neutralizing antibody responses in this subpopulation of patients may be involved in the immunopathogenesis of AIDS encephalopathy.

AIDS Dementia Complex↗
PubMed1991

Experimental Creutzfeldt-Jakob disease: light microscopic, immunohistochemical and ultrastructural studies of the Fujisaki strain of Creutzfeldt-Jakob disease virus in NIH Swiss mice.

Ultrastructural findings in mice terminally affected with the Fujisaki strain of Creutzfeldt-Jakob disease virus are reported. Spongiform vacuolation, extensive myelin and axonal lesions and neuroaxonal dystrophy accompanied by abundant astrocytic gliosis comprise the pattern of the pathological changes at the ultrastructural level. Neuronal intranuclear inclusions and swelling of the astrocytic and dendritic processes were unspecific findings also observed in control animals.

Animals↗
PubMed1990

Detection of measles virus genomic sequences in SSPE brain tissue by the polymerase chain reaction.

The polymerase chain reaction (PCR) was modified to detect RNA genomic sequences by generating cDNA copies of these sequences as a preliminary step. Oligonucleotide primer pairs complementary to sequences in each of the five major structural protein genes of the measles virus (nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, and hemagglutinin protein) were synthesized. PCR products were tentatively identified by visualization of bands of the appropriate size by ethidium bromide staining after gel electrophoresis, and identity was confirmed by subsequent restriction enzyme cleavage of the products at predetermined sites to yield fragments of predicted size. This method successfully amplified 400-500 base regions from each of these five genes in RNA extracts of wild measles virus cultured in Vero cells and in RNA extracted from most of the SSPE brain tissues tested, but not in RNA from any control brain tissues. Measles virus genome was detected in SSPE brain tissues stored frozen for as long as 27 years and formalin-fixed paraffin-embedded subacute sclerosing panencephalitis (SSPE) brain tissues as old as 9 years. This method provides a simple, rapid and highly sensitive means of detecting and identifying sequences of RNA genomes by PCR. The success of this method in detecting measles virus in SSPE brain tissue suggests that PCR is appropriate to investigate the possible presence of RNA viruses in other neurological disorders of unknown etiology.

Adolescent↗
PubMed1990

Appearance of tubulovesicular structures in experimental Creutzfeldt-Jakob disease and scrapie precedes the onset of clinical disease.

We have consistently observed tubulovesicular structures in brain tissues during the terminal stages of naturally occurring and experimentally induced spongiform encephalopathies, irrespective of the host species and virus strain. In NIH Swiss mice inoculated intracerebrally or intraocularly with the Fujisaki strain of Creutzfeldt-Jakob disease (CJD) virus, tubulovesicular structures, measuring 20-50 nm in diameter, were particularly prominent in dilated, pre- and postsynaptic neuronal processes, occasionally being mixed with synaptic vesicles. These structures appeared 13 weeks following intracerebral inoculation, 5 weeks before the onset of clinical signs, when spongiform changes were also detected. The number and density of tubulovesicular structures increased steadily during the course of clinical disease, and were particularly abundant in mice 47 to 51 weeks after intraocular inoculation. In hamsters infected with the 263 K strain of scrapie virus, these structures were initially detected 3 weeks following intracerebral inoculation and increased dramatically at 10 weeks postinoculation. The appearance of tubulovesicular structures before the onset of overt disease in mice inoculated with CJD virus by either the intracerebral or intraocular route, and before the appearance of other neuropathological changes in hamsters infected with scrapie virus, indicate that they represent either a part or aggregate of the infectious virus or a pathological product of the infection.

Animals↗
PubMed1990

Spread of Creutzfeldt-Jakob disease virus along visual pathways after intraocular inoculation.

We studied the targeting of spongiform lesions within the visual pathways after intraocular injection with the Fujisaki strain of Creutzfeldt-Jakob disease (CJD) virus. The first lesions were observed 18 weeks postinoculation in the most superficial layer of the superior colliculus and in the lateral geniculate body contralateral to the side of the inoculation. Asymmetrical lesions in the superior colliculus were found also in mice sacrificed at 19, 22, and 27 weeks postinoculation. These results demonstrate that CJD virus spreads within the CNS via central axons of the visual pathways following intraocular inoculation.

Animals↗
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

Reevaluation of the ultrastructural pathology of experimental Creutzfeldt-Jakob disease. Serial studies of the Fujisaki strain of Creutzfeldt-Jakob disease virus in mice.

We describe the serial ultrastructural pathology of experimental Creutzfeldt-Jakob disease (CJD) in mice. Spongiform vacuoles, widespread myelin and axonal pathology, accompanied by abundant macrophagic reaction and neuroaxonal dystrophy, were consistently found in mice infected with CJD virus. By contrast, intranuclear vacuolation and swelling of astrocytic and neuronal processes were nonspecific changes that also occurred in control animals. We conclude that CJD-related neuropathological phenomena do not accumulate gradually through the incubation period but develop relatively abruptly and in complete form.

Animals↗
PubMed1990

Coexistence of Creutzfeldt-Jakob disease and Alzheimer's disease in the same patient.

We report the case of a 73-year-old patient in whom a diagnosis of Creutzfeldt-Jakob disease, suggested by the clinical course, was verified by the neuropathologic finding of widespread spongiform change and astrogliosis, the presence of proteinase-resistant protein in brain extracts, and the experimental transmission of spongiform encephalopathy to primates inoculated with brain tissue. However, neuropathologic examination also revealed a profusion of senile and neuritic plaques and neurofibrillary tangles that reacted with antibody to the amyloid beta-protein characteristic of Alzheimer's disease, but not with antibody to the scrapie amyloid protein characteristic of Creutzfeldt-Jakob disease.

Aged↗
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

Steroid-responsive myeloneuropathy in a man dually infected with HIV-1 and HTLV-I.

Two human retroviruses, HIV-1 and HTLV-I, have been associated with myelopathies in addition to other neurologic disorders. We report an American dually infected with HIV-1 and HTLV-I who developed steroid-responsive myeloneuropathy. This 28-year-old bisexual man developed interstitial pneumonitis and a transient midthoracic sensory level followed by the evolution of a slowly progressive spastic paraparesis and sensorimotor neuropathy. Serologic studies demonstrated coinfection with both HIV-1 and HTLV-I. Peripheral blood absolute CD4 count was persistently within the normal range. Cranial MRI was normal and spinal MRI showed T3-T10 atrophy. Serial CSF analyses demonstrated marked intrathecal synthesis of anti-HTLV-I IgG, lymphocytic pleocytosis, elevated protein and immunoglobulin G, and oligoclonal bands. HIV-1 was isolated from CSF but not from peripheral nerve. Lymphoproliferative studies confirmed spontaneous proliferation in both blood and CSF. Soluble interleukin 2 receptor and soluble CD8 were greatly elevated in blood and CSF when compared with patients with HIV-related vacuolar myelopathy and seronegative patients with other causes of myelopathy. Nerve biopsy showed epi- and endoneurial CD8+ lymphocytic infiltration without vasculitis; muscle biopsy showed features of acute and chronic denervation. A 6-week course of prednisone produced sustained improvement in leg strength and walking times. We speculate that the myeloneuropathy was caused by HTLV-I in the setting of coinfection with HIV-1.

AIDS Dementia Complex↗
PubMed1990

Change in a public sector health setting: some factors contributing to success.

The differential impact of two action research projects involving the implementation of change in a public sector psychiatric health setting was examined. Particular factors which influenced the projects were the political and policy environment and the internal organisational culture. Implications for the management of change and for the policy implementation process are discussed.

Catchment Area, Health↗
PubMed1990

[HTLV-I retrovirus in Chile: study on 140 neurological patients].

We screened 140 patients with different neurological diseases for the presence of anti HTLV-1 virus antibodies. ELISA test confirmed with Western Blot analysis was performed in CSF and blood. Positive findings were obtained in 23 out of 52 patients with progressive spastic paraparesis (44%). All patients with multiple sclerosis, polymyositis, amyotrophic lateral sclerosis or chronic polyneuropathy were negative. Patients with progressive spastic paraparesis and positive HTLV-1 antibodies were most commonly women (78%) and middle aged (mean 46 years old), with a history of surgical interventions (70%) or blood transfusion (35%). A slowly progressive spastic paraparesis with asymmetric onset and minimal sensory complaints was observed in some cases. Mononuclear pleocytosis in the CSF was observed in 35% with an increased IgG index in 88%. A delayed latency and low amplitude of somatosensory evoked potentials was observed in 89% of patients.

Adolescent↗