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C J Gibbs

Publications and source records attributed to C J Gibbs.

At least 73 records · Page 4Linked to original sources
PubMed1992

Seroprevalence and cofactors of HTLV-I infection in Tumaco, Colombia.

This study presents an analysis of the factors associated with HTLV-I seroprevalence in the endemic area of Tumaco, Colombia. During June to August 1988, 1,077 individuals were selected at random from a population of 45,594. The overall prevalence rate of HTLV-I antibodies was 2.8%. Among females prevalence was significantly higher (p less than 0.02) than among males. Rates increased substantially with age. HTLV-I prevalence among individuals with history of use of intravenous medications was significantly higher (p less than 0.001) than in those without such history. Logistic regression analysis included age in years, indicators for male gender, and for i.v. injections, and their interactions. Age was very strongly associated to HTLV-I infection among females. At early ages prevalence was not different between sexes, but females presented a significantly higher rate than males after age 42. History of i.v. administered medications was very strongly associated in the univariate analysis and, although significance was borderline in the multivariate analysis, it had the effect of doubling the odds of HTLV-I infection.

Adolescent↗
PubMed1992

Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene.

An American family of English origin with an unusually early onset and long-duration form of Creutzfeldt-Jakob disease (CJD) had a heterozygous insert mutation in the region of repeating octapeptide coding sequences between codons 51 and 91 of the PRNP gene on chromosome 20. Affected members were 23 to 35 years old at the onset of illnesses that lasted from 4 to 13 years, yet experimental transmission of disease from the proband (11-year duration) produced a typically brief incubation period and duration of illness in each of three inoculated primates. Also, the PrP amyloid protein that accumulates in CJD brain was only barely detectable in extracted brain tissue from one case with massive spongiform change and was undetectable in another case with no spongiform change, perhaps because of epitope shielding by a configurational change in the protein induced by the mutation. Analysis of this and other families with similar inserts suggests that such mutations in the PRNP gene not only predispose to CJD, but also modify its phenotypic expression.

Adult↗
PubMed1992

HTLV-I DNA sequences in CNS tissue of a patient with tropical spastic paraparesis and HTLV-I-associated myelopathy.

Human T cell lymphotrophic virus type I (HTLV-I) is the etiologic agent of adult T cell lymphoma/leukemia (ATLL) and tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). We studied an HTLV-I-seropositive, white man diagnosed in 1977 with ATLL and 10 years later, 6 months prior to his death, with TSP/HAM. Sections of brain, spinal cord, and visceral tissues were examined histologically, immunohistochemically, by in situ hybridization, and by the polymerase chain reaction (PCR). PCR amplification of a region of the polymerase (pol) gene of HTLV-I from visceral tissue demonstrated the presence of proviral HTLV-I DNA in paraffin-embedded sections from the liver and in DNA extracted from frozen sections of kidney and spleen, but failed to demonstrate viral sequences in paraffin sections of the lung and a lymph node. PCR analysis of CNS tissue demonstrated viral sequences in regions of the brain including frozen samples from cerebellum and cerebral cortex and paraffin sections of the thoracic spinal cord, but failed to detect proviral DNA in sections from a region in the lumbar cord. These results map the distribution of HTLV-I DNA sequences in the CNS of a patient with TSP/HAM for 3 months.

Blotting, Northern↗
PubMed1991

Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene.

The PRNP gene, encoding the amyloid precursor protein that is centrally involved in Creutzfeldt-Jakob disease (CJD), has an unstable region of five variant tandem octapeptide coding repeats between codons 51 and 91. We screened a total of 535 individuals for the presence of extra repeats in this region, including patients with sporadic and familial forms of spongiform encephalopathy, members of their families, other neurological and non-neurological patients, and normal controls. We identified three CJD families (in each of which the proband's disease was neuropathologically confirmed and experimentally transmitted to primates) that were heterozygous for alleles with 10, 12, or 13 repeats, some of which had "wobble" nucleotide substitutions. We also found one individual with 9 repeats and no nucleotide substitutions who had no evidence of neurological disease. These observations, together with data on published British patients with 11 and 14 repeats, strongly suggest that the occurrence of 10 or more octapeptide repeats in the encoded amyloid precursor protein predisposes to CJD.

Adult↗
PubMed1991

Observations after human immunodeficiency virus immunization and challenge of human immunodeficiency virus seropositive and seronegative chimpanzees.

Two human immunodeficiency virus (HIV)-seropositive chimpanzees (A-3 and A-86c) infected 4 yr earlier with HIV, along with one uninfected animal (A-36), were inoculated intramuscularly three times in a year with a gamma-irradiated gp120-depleted HIV immunogen in incomplete Freund's adjuvant. Both previously infected animals promptly developed an anamnestic humoral antibody response after the first dose, and the uninfected animal developed a primary humoral response to the first dose and then an anamnestic response to the second dose. Although HIV had been recovered repeatedly from the seropositive animals, they became persistently virus-culture negative at the time of or just before the first inoculation of the immunogen. Intravenous challenge with 40 chimpanzee-infectious-doses of a heterologous HIV strain (HIVIIIB) was done 4 mo after the third inoculation in the three treated chimpanzees and in an untreated control animal (A-189a). The immunized naive animal (A-36) and the unimmunized control (A-189a) became infected, and virus has been isolated from their peripheral blood mononuclear cells for greater than 2 yr after challenge. However, the two previously infected chimpanzees (A-3 and A-86c) resisted challenge and have remained virus negative by peripheral blood mononuclear cell cocultivation for greater than 2 yr of observation after challenge; moreover, no evidence of reinfection was detectable by PCR. Despite the in vivo resistance, however, peripheral blood mononuclear cells from the resistant animals (A-3, A-86c) remained susceptible to infection by HIV in vitro. These findings reveal that a state of immunity can develop and/or be induced to control and/or prevent HIV infection in the chimpanzees. In the absence of any detectable level of neutralizing antibody in A-3 and a low level in A-86c, the patterns of the responses to challenge seen in the four animals suggest that the cell-mediated immune mechanism must have played a significant role in the resistant chimpanzees both in control of their HIV infection and in their resistance to challenge.

Animals↗
PubMed1991

In situ hybridization detection of HTLV-I RNA in peripheral blood mononuclear cells of TSP/HAM patients and their spouses.

This is the first report of the direct detection of HTLV-I RNA in uncultured peripheral blood mononuclear cells (PBMNC's) of patients with tropical spastic paraparesis and HTLV-I-associated myelopathy (TSP/HAM) and their spouses, using the technique of in situ hybridization. Twenty-one Colombian patients were tested, all of whom had antibodies to HTLV-I; the presence of HTLV-I proviral DNA in their PBMNC's was confirmed by the polymerase chain reaction technique. Of the 21 patients 15 had a clinical diagnosis of tropical spastic paraparesis (TSP/HAM), 5 were asymptomatic relatives, and 1 patient had leukemia. In situ hybridization was positive in samples from 5 patients; 2 of these were TSP/HAM patients and the other 3 were healthy wives of TSP/HAM patients. This study demonstrates for the first time that viral RNA is expressed in uncultured PBMNC's of some patients with TSP/HAM in whom proviral DNA is also present; furthermore, the detection of HTLV-I RNA in the blood of female partners of TSP/HAM patients clearly illustrates the high likelihood of HTLV-I transmission through sexual contact.

Cell Line↗
PubMed1991

Detection of flaviviruses by reverse-transcriptase polymerase chain reaction.

RNA sequences of five flaviviruses were detected by a modified polymerase chain reaction (PCR) that incorporated a reverse transcriptase and RNase inhibitor. Oligonucleotide primer pairs were synthesized to amplify sequences from St. Louis encephalitis (SLE), Japanese encephalitis (JBE), yellow fever (YF), dengue 2 (DEN-2), and dengue 4 (DEN-4) viruses. The amplified products were visualized as bands of appropriate size on ethidium bromide-stained agarose gels. The identity of these products was confirmed by restriction endonuclease cleavage to generate fragments of predicted lengths. The reverse-transcriptase PCR (RT-PCR) successfully amplified flavivirus sequences from cell cultures, frozen brain tissue, and formalin-fixed, paraffin-embedded brain tissue. The reactions were highly specific, and the method compared favorably to two conventional assays of viral infectivity. RT-PCR followed by PCR with nesting primers (N-PCR) was 1,000-fold more sensitive in detecting virus than classical infectivity titration by intracerebral inoculation of suckling mice and nearly 1,000-fold more sensitive than amplification of virus in cell culture followed by inoculation of mice.

Aedes↗
PubMed1991

The phenotypic expression of different mutations in transmissible familial Creutzfeldt-Jakob disease.

Cases of familial Creutzfeldt-Jakob disease (CJD) with mutations in the PRNP gene were analyzed for distinctive clinico-pathological and experimental transmission characteristics. An insert mutation within the region of codons 51 to 91 was associated with a markedly early age at onset and prolonged course of illness. Point mutations at codons 178 and 200 were also associated with ages at onset, durations of illness, and clinical symptom profiles that differed from sporadic CJD. The age at onset of illness in each group was correlated with the length of incubation periods in primates inoculated with their brain tissue, suggesting that the early onset of familial CJD results not from a time shift of the initiating event, but from an accelerated pre-clinical (incubation) phase of disease, perhaps due to a more rapid formation of amyloid induced by a mutationally-altered precursor protein template.

Adult↗
PubMed1991

Mechanism of the damage to myelinated axons in experimental Creutzfeldt-Jakob disease in mice: an ultrastructural study.

We report the ultrastructural pathology of myelinated axons in mice infected experimentally with the Fujisaki strain of Creutzfeldt-Jakob disease (CJD). Initially the myelin sheath was separated into several concentric bands, and cellular processes penetrated between layers of myelin and lifted away the outermost lamella. Then a complicated labyrinth of the concentric cellular processes, clearly belonging to either astrocytes or macrophages, invested myelinated axons. In terminal stages axons completely denuded of myelin were seen in the center of concentric networks of cellular processes. Myelin remnants were seen within astrocytes and macrophages. We conclude that the mechanism(s) of damage to myelinated axons in CJD may be similar to that operating in immunologically mediated demyelinating disorders.

Animals↗
PubMed1991

Transmission of human T-cell leukemia virus type I from a patient with HTLV-I associated myelopathy/tropical spastic paraparesis and an asymptomatic carrier to rabbits.

Rabbits were infected successfully with two strains of human T-cell leukemia virus type I (HTLV-I), one isolated from a Colombian patient with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and the other from an asymptomatic carrier. HTLV-I was repeatedly demonstrated in peripheral blood mononuclear cells (PBMNC) of infected rabbits, and the rabbits had elevated antibodies against the various structural proteins of HTLV-I. Four rabbits inoculated with HTLV-I-infected autologous lymphoid cells intravenously (i.v.) and intracerebrally (i.c.) had virus present in their PBMNC for more than 40 weeks, while those that were inoculated either with HTLV-I-infected human lymphoid cells or with autologous rabbit lymphoid cells intraperitoneally (i.p.) had episodes during which virus was not recovered from their PBMNC. The one rabbit inoculated i.p. developed antibodies to viral envelope glycoproteins earlier than did those inoculated i.v. and i.c. Rabbit lymphoid cell lines persistently infected with HTLV-I were established by cocultivating the rabbit PBMNC with HTLV-I-infected human lymphoid cells that had been irradiated or by inoculation with cell-free supernatant fluids of HTLV-I infected non-irradiated lymphoid cell cultures. HTLV-I-infected rabbit cell lines were of T-cell origin and expressed HTLV-I antigens by immunofluorescence. Electron microscopy revealed type-C retrovirus particles.

Adult↗
PubMed1991

The molecular genetics of familial Creutzfeldt-Jakob disease in France.

Five French families with Creutzfeldt-Jakob disease (CJD) were found to have either of 2 different point mutations (at codons 178 and 200) in the amyloid precursor gene (PRNP) on chromosome 20. The ancestry of these and other CJD families outside of France suggests that the codon 178 mutation had a northern European origin, while the codon 200 mutation originated in central Europe and the Mediterranean basin. Evidence is presented that the mutations either cause or predispose to familial forms of CJD, and also influence their phenotypic expression, although considerable clinical and neuropathological heterogeneity may occur between and even within families having the same mutation. Experimental transmission of disease was successful in 4 of 5 inoculated cases, comparable to the transmission rate in sporadic CJD.

Amyloid beta-Protein Precursor↗
PubMed1991

HLA-DR expression in macaque neuroendothelial cells in vitro and during SIV encephalitis.

HLA-DR expression in neuroendothelial cells (NEC) was studied during the course of SIV encephalitis in rhesus monkeys. HLA-DR determinants were detected on NEC in monkeys with SIV encephalitis, but not in control animals. In situ hybridization with an SIV probe indicated that HLA-DR expression was not a consequence of SIV replication within NEC. Cultured rhesus NEC stimulated with gamma interferon expressed HLA-DR to a higher degree than cultured brain fibroblasts or astrocytes. These data support the contention that NEC participate in retrovirus-induced inflammation and autoimmunity within the central nervous system.

Animals↗
PubMed1991

Preclinical and clinical studies on immunogenicity and safety of the HIV-1 p17-based synthetic peptide AIDS vaccine--HGP-30-KLH.

Immunization with a synthetic HIV-1 p17 peptide analog (HGP-30; aa 85-115 of HIV p17), coupled to a carrier protein (KLH, keyhole limpet hemocyanin) given with alum as the adjuvant induces antibodies which cross-react with both HGP-30 and HIV p17 and clones of cytotoxic and helper T-cells which recognize HGP-30 and HIV p17. Proliferation of lymphocytes in response to HGP-30 has been observed in mice, in HIV-infected individuals and in healthy HIV-seronegative volunteers vaccinated with the p17-based synthetic peptide construct. Cytotoxic T-cell responses against EBV transformed, recombinant p17 pulsed targets were observed using antigen-expanded PBLs from HGP-30-KLH immunized individuals. These results are consistent with predictions that the HGP-30 domain of HIV p17 contains both T- and B-cell epitopes that are recognized by animals and humans. In preclinical toxicology studies in animals and in initial clinical trials in humans the synthetic peptide construct (HGP-30-KLH/alum) has been shown to be safe. This paper summarizes the preclinical immunogenicity and safety data for HGP-30-KLH and presents the initial results from the first Phase 1 clinical trial.

AIDS Vaccines↗
PubMed1991

Differences in the membrane interaction of scrapie amyloid precursor proteins in normal and scrapie- or Creutzfeldt-Jakob disease-infected brains.

The membrane interaction and hydrophobicity of the normal (PrPC) and infectious isoform (PrPSc/CJD) of scrapie and Creutzfeldt-Jakob disease amyloid precursor proteins was studied. The normal isoform of hamster and human scrapie amyloid precursor protein was found on the microsomal/synaptosomal membranes anchored solely by the C-terminal glycolipid. Glycolipid cleavage resulted in dissociation from the membranes and change of behavior from a highly hydrophobic to a hydrophilic protein, susceptible to proteases. In contrast, the PrPSc/CJD isoform was resistant to release by glycolipid-cleaving enzymes. A part of PrPSc/CJD was released from the membranes after prolonged trypsin treatment, yielding a further protease-resistant product of 27-30 kDa. The results demonstrate the proteolytic resistance of the membrane-bound PrPSc/CJD isoform and also indicate the presence of a different, apparently disease-induced mechanism of membrane interaction in the scrapie- and CJD-infected microsomal and synaptosomal membranes.

Animals↗
PubMed1991

Combination ultrafiltration and 6 M urea treatment of human growth hormone effectively minimizes risk from potential Creutzfeldt-Jakob disease virus contamination.

Although genetically engineered human growth hormone (hGH) is now commercially available, native pituitary-derived hGH is still used by physicians in many countries for the treatment of hormone deficiency states. We describe a method using ultrafiltration and 6 M urea that reduced infectivity in human pituitary tissue that had been deliberately contaminated with scrapie virus (an animal analogue of human Creutzfeldt-Jakob disease virus) from an initial level of 10(9.7) infectious units to just 5 infectious units. Based on estimates of the frequency of contamination and infectivity levels in batches of human pituitaries, the use of this protocol to prepare GH from cadaveric human glands yields a calculated probability of exposure to a contaminated vial of not greater than 1 in 3.2 million recipients; therefore, native hormone prepared by this method may be considered to be essentially risk-free. The same methodology may be useful in the preparation of other hormones, such as prolactin, for which no synthetic substitutes are currently available, as well as biological products derived from sheep or cattle, that may be infected with scrapie or bovine spongiform encephalopathy.

Animals↗