Search PubMed⌕ Search

Biomedical subjects

C J Gibbs

Publications and source records attributed to C J Gibbs.

At least 37 records · Page 2Linked to original sources
PubMed1996

HLA DRB1*DQB1* haplotype in HTLV-I-associated familial infective dermatitis may predict development of HTLV-I-associated myelopathy/tropical spastic paraparesis.

A possible causal association between infective dermatitis and HTLV-I infection was reported in 1990 and confirmed in 1992. We now report familial infective dermatitis (ID) occurring in a 26-year-old mother and her 9-year-old son. The mother was first diagnosed with ID in 1969 at the age of 2 years in the Dermatology Unit at the University Hospital of the West Indies (U.H.W.I.) in Jamaica. The elder of her 2 sons was diagnosed with ID at the age of 3 years, also at U.H.W.I. Both mother and son are HTLV-I-seropositive. A second, younger son, currently age 2 years, is also HTLV-I-seropositive, but without clinical evidence of ID. Major histocompatibility complex (MHC), class II, human leucocyte antigen (HLA) genotyping documented a shared class II haplotype, DRB1*DQB1* (1101-0301), in the mother and her 2 sons. This same haplotype has been described among Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and has been associated with a possible pathologically heightened immune response to HTLV-I infection. The presence of this haplotype in these familial ID cases with clinical signs of HAM/TSP may have contributed to their risk for development of HAM/TSP. The unaffected, HTLV-I-seropositive younger son requires close clinical follow-up.

Adult↗
PubMed1996

Widespread, restricted low-level measles virus infection of brain in a case of subacute sclerosing panencephalitis.

In situ reverse transcriptase-polymerase chain reaction amplification with labeled-probe hybridization (in situ RT-PCR/LPH) was used to detect measles virus RNA within formalin-fixed, paraffin-embedded brain tissue sections from a patient who died with subacute sclerosing panencephalitis (SSPE). Many more infected neurons and oligodendrocytes were detected by in situ RT-PCR/LPH than by immunohistochemistry or by in situ hybridization alone. In addition, infection of vascular endothelial cells was demonstrated only by in situ RT-PCR/LPH. The observation that many cells contained only a few copies of viral RNA without detectable antigen is consistent with a persistent viral infection of the central nervous system. In situ RT-PCR/LPH, combining the sensitivity of PCR with the tissue localization of in situ hybridization, should prove useful in further studies to detect nucleic acids in situ in the central nervous system.

Adolescent↗
PubMed1996

Spontaneous healing of osteitis fibrosa cystica in primary hyperparathyroidism.

A 24-year-old man with primary hyperparathyroidism and osteitis fibrosa cystica developed acute hypocalcaemia. Spontaneous healing of his bone disease was confirmed radiographically and by correction of the serum alkaline phosphatase. Hypercalcaemia associated with a raised serum parathyroid hormone recurred 90 weeks after the initial presentation. During the fourth neck exploration a parathyroid adenoma was removed, resulting in resolution of his condition. Haemorrhagic infarction of an adenoma was the most likely cause of the acute hypocalcaemic episode.

Acute Disease↗
PubMed1996

Increased quinolinate immunoreactivity in the peripheral blood monocytes/macrophages from SIV-infected monkeys.

Quinolinate (QUIN), a metabolite in the kynurenine pathway of tryptophan degradation and a neurotoxin that is thought to act through the NMDA receptor system, was localized in cultured peripheral blood monocytes/macrophages from SIV-infected monkeys using a recently developed immunohistochemical method. Significant increases in QUIN immunoreactive (IR) cells were detected in all five SIV-infected monkeys examined. Multinucleated giant cells, a hallmark of lentiviral infection, were visible in selected samples. Treatment with the QUIN precursors, tryptophan and kynurenine, increased the number of QUIN-IR cells in both the control and SIV-infected preparations, perhaps by a mass action mechanism. We hypothesize that in SIV-infected monkeys, infiltrating monocytes/macrophages contribute to the high level of brain QUIN and associated neuropathology.

Animals↗
PubMed1996

Anterior horn cell degeneration in polymyositis associated with human T lymphotropic virus Type-1 in patients from Barbados.

Anterior horn cell degeneration has only occasionally been noted in patients with tropical spastic paraparesis associated with human T lymphotropic virus type-1 (HTLV-1) infection. We report on three adult patients with HTLV-1-associated polymyositis who had clinical evidence of anterior horn cell degeneration. One patient had moderate proximal weakness and muscle wasting in all four limbs, while two had mild upper limb weakness with more profound proximal weakness and wasting in the lower limbs. In all three patients, electromyographic findings were compatible with motor unit loss and muscle biopsies showed mononuclear inflammatory cell infiltration; muscle biopsies in two patients showed features of denervation. Immunoglobulin G (IgG) antibodies to HTLV-1 were detected by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western immunoblot in serum and cerebrospinal fluid in all three patients. In two, cell cultures were established from peripheral blood lymphocytes and HTLV-1 antigen was identified by immunofluorescence and the ELISA antigen-capture technique using an anti-p19 HTLV-1 mouse monoclonal antibody. The three cases illustrate the variety of neuromuscular disease, other than spastic paraparesis, that may occur in HTLV-1 infection. In some cases of HTLV-1-associated polymyositis, anterior horn cell degeneration may make a significant contribution to the muscle atrophy observed.

Adult↗
PubMed1995

Identification of human T cell leukemia/lymphoma virus type I antibodies, DNA, and protein in patients with polymyositis.

OBJECTIVE: To investigate a possible association between human T cell leukemia/lymphoma virus type I (HTLV-I) and polymyositis (PM). METHODS: Sera and muscle biopsy samples from 9 Jamaican PM patients were compared with specimens from American HTLV-I-positive PM patients and normal controls. Sera were evaluated for HTLV antibodies by enzyme-linked immunosorbent assay and Western blot. The biopsy samples were analyzed for HTLV-I/II DNA by polymerase chain reaction and were also immunohistochemically stained for HTLV gp46 envelope protein. RESULTS: Seven of the 8 Jamaican PM patients from whom sera were available were HTLV-I seropositive. The muscle biopsies of all 9 Jamaican patients demonstrated severe lymphocytic infiltration, cellular degeneration, myofiber atrophy, and fibrosis. Each muscle biopsy specimen contained HTLV-I DNA. Two of 6 samples demonstrated intense staining for HTLV-I gp46 in many of the invading mononuclear cells and weak staining for HTLV-I gp46 in many of the invading mononuclear cells and weak staining in the adjacent myocytes. Two other specimens were weakly positive for gp46 in rare mononuclear cells. All control specimens were negative for the presence of HTLV-I DNA and protein. CONCLUSION: HTLV-I is associated with an inflammatory muscle disease characterized by direct invasion of the affected muscle by HTLV-I-infected mononuclear cells.

Adult↗
PubMed1995

Western blot mapping of disease-specific amyloid in various animal species and humans with transmissible spongiform encephalopathies using a high-yield purification method.

SAF-protein, an amyloid, is the main constituent of scrapie-associated fibrils (SAF) and a specific marker for transmissible spongiform encephalopathies (TSE). Using an improved extraction method and Western blot detection, the disease-specific amyloid was found in various parts of the central nervous system of hamsters orally infected with scrapie, of squirrel monkeys orally infected with kuru, sporadic Creutzfeldt-Jakob disease (CJD) and scrapie, of human patients with sporadic CJD, of a sheep with natural scrapie and of a cow with bovine spongiform encephalopathy (BSE). In human CJD samples, the concentration of TSE-specific amyloid was estimated to be 1000- to 10 000-fold lower than in the central nervous system of hamsters with scrapie. The extraction method has a yield of 70% and allows Western blot detection of the TSE-specific amyloid in samples representing 1-10 micrograms of brain tissue from intracerebrally infected hamsters, as well as in individual spleens from hamsters with terminal scrapie infected by the intracerebral, oral or intraperitoneal route. A 20-100 mg sample of material is sufficient for the extraction of the pathological protein from different rodent, monkey, ovine, bovine and human tissues. The results reported here demonstrate the potential suitability of the method for the routine diagnosis of TSE as well as for the detailed analysis of distribution patterns of the TSE-specific amyloid in experimental approaches to the investigation of these diseases.

Amyloid↗
PubMed1994

Infectious amyloid precursor gene sequences in primates used for experimental transmission of human spongiform encephalopathy.

Based on the analysis of genomic DNA from single healthy animals of each of five primate species, nucleotide and predicted amino acid sequences of the infectious amyloid precursor gene of higher apes (Gorilla and Pan) and Old World (Macaca) and New World (Ateles, Saimiri) monkeys showed 95-99% homology to the human sequences, corresponding to their phylogenetic distance from humans. Two of 18 amino acids that differed from humans resulted from nucleotide changes at sites of mutations in humans with familial forms of spongiform encephalopathy (a deleted codon within the codon 51-91 region of 24 bp repeats and a substitution at codon 198). In each of the five animals, codon 129 specified methionine, the more common of the two polymorphic genotypes in humans. Because genotypic homology did not correlate with experimental transmission rates of human spongiform encephalopathy, primary structural similarity of the infectious amyloid precursor protein in humans and experimental primates may not be an important factor in disease transmissibility.

Amino Acid Sequence↗
PubMed1994

Scrapie amyloid (prion) protein has the conformational characteristics of an aggregated molten globule folding intermediate.

The scrapie amyloid (prion) protein (PrP27-30) is a host-derived component of the infectious scrapie agent; the potential to replicate, propagate, and form amyloid is a result of the posttranslational event or conformational abnormality. In low concentrations of guanidine hydrochloride (Gdn.HCl), PrP27-30 dissociates into a compact equilibrium intermediate with a substantial portion of secondary structure, partially denatured tertiary structure, and tryptophan residues in an apolar environment [Safar, J., Roller, P. P., Gajdusek, D. C., & Gibbs, C. J., Jr. (1993) J. Biol. Chem. 27, 20276-20284]. Here we describe the characteristics of this metastable form as monitored by 8-anilino-1-naphthalenesulfonate (ANS) fluorescence spectroscopy and circular dichroism (CD) spectroscopy, and we propose a mechanism for scrapie amyloid association. The Gdn.HCl-induced equilibrium intermediate of PrP27-30 had multiple high-affinity hydrophobic binding sites for ANS, some close to the Trp residues. The amide CD spectrum of an acid-induced intermediate (A-form), in equilibrium at pH < 2.0, was similar to the Gdn.HCl-induced intermediate and suggested the presence of a significant portion of an alpha-helical or beta-turn secondary structure. In contrast, the PrP27-30 associated into aggregates in an all beta-sheet conformation with less ordered and more exposed hydrophobic side chains. The noncooperative unfolding of the Gdn.HCl-induced intermediate at high temperature was irreversible and correlated with the loss of infectivity. The results demonstrate that PrP27-30 associates through a compact, metastable hydrophobic intermediate with an nonnative, nondenatured secondary structure and a tertiary structure close to the unfolded form.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilino Naphthalenesulfonates↗
PubMed1994

Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease.

We present a synthesis of clinical, neuropathological, and biological details of the National Institutes of Health series of 300 experimentally transmitted cases of spongiform encephalopathy from among more than 1,000 cases of various neurological disorders inoculated into nonhuman primates during the past 30 years. The series comprises 278 subjects with Creutzfeldt-Jakob disease, of whom 234 had sporadic, 36 familial, and 8 iatrogenic disease; 18 patients with kuru; and 4 patients with Gerstmann-Strüssler-Scheinker syndrome. Sporadic Creutzfeldt-Jakob disease, numerically by far the most important representative, showed an average age at onset of 60 years, with the frequent early appearance of cerebellar and visual/oculomotor signs, and a broad spectrum of clinical features during the subsequent course of illness, which was usually fatal in less than 6 months. Characteristic spongiform neuropathology was present in all but 2 subjects. Microscopically visible kuru-type amyloid plaques were found in 5% of patients with Creutzfeldt-Jakob disease, 75% of those with kuru, and 100% of those with Gerstmann-Sträussler-Scheinker syndrome; brain biopsy was diagnostic in 95% of cases later confirmed at autopsy, and proteinase-resistant amyloid protein was identified in Western blots of brain extracts from 88% of tested subjects. Experimental transmission rates were highest for iatrogenic Creutzfeldt-Jakob disease (100%), kuru (95%), and sporadic Creutzfeldt-Jakob disease (90%), and considerably lower for most familial forms of disease (68%). Incubation periods as well as the durations and character of illness showed great variability, even in animals receiving the same inoculum, mirroring the spectrum of clinical profiles seen in human disease. Infectivity reached average levels of nearly 10(5) median lethal doses/gm of brain tissue, but was only irregularly present (and at much lower levels) in tissues outside the brain, and, except for cerebrospinal fluid, was never detected in bodily secretions or excretions.

Adolescent↗
PubMed1994

The consistent use of organic solvents for purification of phospholipids from brain tissue effectively removes scrapie infectivity.

A procedure for the purification of phospholipids from brain tissue was evaluated for its efficacy in eliminating scrapie agent infectivity. The key feature of the process was that phospholipids were extracted and purified by exclusive use of organic solvents. Experiments were done by in vivo animal bioassay on a scaled-down version of the original procedure using 263 K-infected hamster brains as source material. The absence of any detectable infectivity in the final preparations indicated that organic solvent extraction is acceptable for purification and decontamination of biological products from scrapie-like agents provided that only the organic phase is used.

Animals↗
PubMed1994

Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.

Animals↗
PubMed1993

Sequence analysis of an immunogenic and neutralizing domain of the human T-cell lymphoma/leukemia virus type I gp46 surface membrane protein among various primate T-cell lymphoma/leukemia virus isolates including those from a patient with both HTLV-I-associated myelopathy and adult T-cell leukemia.

Human T-cell lymphoma/leukemia virus type I (HTLV-I) causes adult T-cell leukemia/lymphoma and HTLV-I-associated myelopathy. Specific regions within the outer envelope proteins of other retroviruses, e.g., human immunodeficiency virus type 1, are highly immunogenic and, because of the selective pressure of the host immune system, quite variable. Mutations in the external envelope protein gene of murine retroviruses and human immunodeficiency virus type 1 influence cellular tropism and disease pathogenesis. By contrast, no disease-specific viral mutations have been identified in HTLV-I-infected patients. However, all isolates studied thus far have originated from leukemic cell lines, peripheral blood mononuclear cells, or cerebrospinal fluid lymphocytes from patients with HTLV-I-associated myelopathy and adult T-cell leukemia/lymphoma and, therefore, may not truly reflect tissue-associated variation. The midregion of the HTLV-I gp46 external envelope glycoprotein (amino acids 190-209) induces an antibody response in 90% of infected individuals, and a hexapeptide in this region (amino acids 191-196) elicits antibodies in rabbits which inhibit syncytia formation and infection of target lymphocytes. Because of the above, we expected the neutralizing domain of the gp46 env gene of HTLV-I to possess disease or organ-associated mutations selected by the infected host's immune system. Hence, we amplified, cloned, and sequenced HTLV-I DNA directly from in vivo central nervous system, spleen, and kidney specimens, and a leukemic cell line from a patient (M. J.) with both HTLV-I-associated myelopathy and adult T-cell leukemia/lymphoma to discern the possibility of tissue- and/or disease-specific variants. In addition, we sequenced several HTLV-I isolates from different regions of the world, including Papua New Guinea, Bellona, and Liberia, and compared them to other previously published HTLV-I and related retroviral sequences. The 239-base pair sequence corresponding to amino acids 178 to 256 in gp46 displayed minor tissue-specific variation in clones derived from central nervous system tissues from patient M. J., but overall was highly conserved at both the DNA and amino acid levels. Variation was observed in this region among the other HTLV-I, simian T-cell lymphoma virus type I, and HTLV-II isolates in a pattern that was consistent with their known phylogenetic relationship. No consistent disease-related changes were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1993

Conformational transitions, dissociation, and unfolding of scrapie amyloid (prion) protein.

The infectious form of the scrapie amyloid (prion) precursor, PrPSc, is a host-derived protein and a component of the infectious agent causing scrapie. PrPSc and the carboxyl-terminal proteinase K resistant core, PrP27-30, have the potential to form amyloid as a result of a post-translational event or conformational abnormality. We have studied the conformational transitions of both proteins reconstituted into liposomes, associated in solid state in thin films, and dissociated by guanidine HCl. The secondary structure of PrPSc in liposomes deduced from analysis of circular dichroism spectra contained approximately 34% beta-sheets, approximately 20% alpha-helix, and approximately 46% beta-turns and random coil. Cleavage of the amino-terminal region of PrPSc resulted in all-beta PrP27-30, with an estimated approximately 43% beta-sheet, no alpha-helix, and approximately 57% beta-turns and random coil. The PrPSC associated in thin films with a tertiary structure perturbation corresponding to unfolding, while the secondary structure was preserved. The PrP27-30 assembled into the solid state with a similar perturbation of tertiary structure but with a large increase in the beta-sheet content, probably due to an intermolecular alignment of the external beta-sheets, or to a secondary structure transition, or both. The various conformational states had little or no impact on infectivity. Equilibrium dissociation and unfolding demonstrated a greater resistance of PrP27-30 to denaturation. The dissociated monomers unfolded through intermediate(s), suggesting the presence of protein domains with distinct secondary structure stabilities. The results provide experimental evidence for the beta-sheet type assembly of scrapie amyloid PrP27-30 in the solid state and demonstrate the importance of amino-terminal cleavage in the stability and alignment of the amyloid-forming monomers.

Amino Acid Sequence↗