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Biomedical subjects

G R Pearson

Publications and source records attributed to G R Pearson.

At least 55 records · Page 3Linked to original sources

Different genomic fragments encode for two human herpesvirus 6 early proteins that share a cross-reactive antigen.

A monoclonal antibody was previously described which precipitated two human herpesvirus 6 early proteins. The experiments reported in this paper were designed to determine the relationship of these two proteins. This was determined by probing enzymatically digested viral DNA with a cloned p41 cDNA construct and with a synthetic p38 oligonucleotide. These probes reacted with genomic fragments of different sizes following enzymatic digestion. In addition, the p38 synthetic probe reacted with uninfected cell DNA. These results indicated that p41 and p38 share an antigenic epitope but are encoded by different genomic fragments.

Amino Acid Sequence↗

Pathological lesions associated with Anoplocephala perfoliata at the ileo-caecal junction of horses.

The intestinal tracts of 20 horses, killed at a local abattoir and of unknown age, sex and previous clinical history were examined for the presence of Anoplocephala perfoliata attached to the ileo-caecal junction. Four horses had no tape-worms, nine had one to 20 tapeworms attached to the mucosa and seven had more than 100 attached to the mucosa. The histological changes of thickening, ulceration and eosinophil infiltration of the mucosa at the ileo-caecal junction were more severe when more than 100 parasites were present.

Abattoirs↗

Identification of T- and B-cell epitopes associated with a restricted component of the Epstein-Barr virus-induced early antigen complex.

Experiments were designed in an attempt to identify T- and B-cell epitopes expressed on the 17-kDa early-antigen-restricted (EA-R) polypeptide of the EBV-induced early antigen complex. Using Berzofsky's algorithm, 3 hypothetical T-cell epitopes on p17 were synthesized and employed in EBV-specific lymphoproliferative assays. Lymphocytes from all EBV-infected donors responded against one of these epitopes (p17.1) irrespective of their serological status relative to antibodies to EA-R. Both CD4+ and CD8+ T-cell subpopulations from seropositive donors proliferated in the presence of p17.1 in short-term cultures. These experiments therefore identified one T-cell epitope on the 17-kDa polypeptide. In contrast, sera from anti-Ea antibody-positive individuals reacted with all 3 synthetic peptides to varying degrees, with p17.1 being the most frequently reactive epitope. When the sera were grouped according to diagnosis, it was noted that 82% of the sera from patients with aggressive lymphomas, whether Africans with Burkitt's lymphoma or North Americans with intermediate-grade large-cell or high-grade B-cell lymphoma, contained antibody reactive with p17.1, while 64% were reactive with p17.2 and 29% with p17.3. In contrast, high anti-EA antibody-positive sera from nasopharyngeal carcinoma patients were relatively less reactive with these synthetic peptides (23% positive with p17.1; 19% with p17.2; and 13% with p17.3). These results therefore identified 3 B-cell EA-R epitopes which might be potentially useful for clinical or epidemiological studies of EBV-associated lymphoproliferative diseases.

Amino Acid Sequence↗

Epstein-Barr virus and nasopharyngeal carcinoma.

The Epstein-Barr virus (EBV) has been studied for over 25 years as a probable cause of certain human cancers, including nasopharyngeal carcinoma (NPC). This is a low-incidence head and neck cancer in Western countries (including the USA), but is the third-leading cancer in males in Southeast Asia. Evidence supporting an etiologic relation between this virus and NPC includes the fact that there is a 100% infection rate in patients with this cancer and that EBV DNA and antigens have been demonstrated in all biopsies examined to date. The determination that EBV is at least a major co-factor in the etiology of NPC has led to the development of new diagnostic and prognostic tests for this disease using anti-viral markers. Of particular importance to the diagnosis of NPC were the findings, initially reported by the Henles [Int J Cancer 17:1-7, 1976], that the serum of patients with NPC contain IgA antibodies to EBV at a high frequency. In general, 80-90% of patients with this disease contain serum IgA antibodies to EBV as opposed to 10-30% of the normal population. This finding has resulted in the development and successful employment of tests measuring this antibody as adjuncts to pathology in the diagnosis of NPC including the occult form. In addition, this finding has resulted in the development of tests for the early detection of this disease. The IgA test for antibodies to EBV is currently employed in large screening programs in Southeast Asia designed to identify those individuals at risk for the development of NPC.(ABSTRACT TRUNCATED AT 250 WORDS)

Herpesvirus 4, Human↗

Stress and the memory T-cell response to the Epstein-Barr virus in healthy medical students.

This study investigated the memory T-cell proliferative response to several early and late Epstein-Barr virus (EBV) polypeptides. Blood samples were collected twice, 1 month before a 3-day block of examinations and again on the last day of the exam series. Ss were 25 healthy, EBV seropositive medical students. The proliferative response to 5 of the 6 EBV polypeptides significantly decreased during examinations. In addition, Ss high (above the median) in seeking support, as measured by the COPE, had lower proliferative responses to 3 EBV polypeptides (p17, p52/50, and p85), as well as higher levels of antibody to EBV virus capsid antigen. The data provide further evidence that psychological stress can modulate the cellular immune response to latent EBV.

Adult↗

An enzyme-linked immunosorbent assay for the measurement of human IgA antibody responses to Epstein-Barr virus membrane antigen.

An enzyme-linked immunosorbent assay (ELISA) which uses a recombinant truncated form of the Epstein-Barr virus (EBV) membrane antigen gp350/250 has been developed and used to measure human IgA antibody responses to that antigen. From comparisons with conventional immunofluorescence assays (IFA) for measuring IgA antibody responses to EBV viral capsid antigens, the ELISA shows comparable specificity and is approximately 4-fold more sensitive. Since IgA antibodies to EBV indicate a high risk of developing nasopharyngeal carcinoma (NPC), the described ELISA, which is more sensitive and objective than IFA, has potential for use in the diagnosis of NPC and for large-scale screening to identify individuals at risk for the development of this disease.

Animals↗

Feline spongiform encephalopathy: fibril and PrP studies.

The brains from 18 cats were examined for the presence of the fibrils and modified PrP protein which are molecular diagnostic markers for scrapie-like diseases. Thirteen cats were referred with clinical neurological signs potentially indicative of feline spongiform encephalopathy (FSE). Of these, five had histopathological changes of FSE, five had other lesions of the central nervous system, and in three the brain was normal. The remaining five cats had no clinical neurological signs and were selected as controls. Fibrils and modified PrP protein were found in the brains of the five cats with FSE and in one of the cats with neurological signs but no histopathological changes in the central nervous system. Fibrils were present in the absence of modified PrP in the brains of two cats, one with neurological signs and a histologically confirmed meningioma, and one with no neurological signs and a histologically normal brain.

Animals↗

Canine distemper infection associated with acute nervous signs in dogs.

Eight vaccinated dogs suddenly developed progressive ataxia, paresis or paralysis of short duration. A histopathological examination revealed a non-suppurative meningoencephalitis suggestive of a viral infection, and immunohistochemical examination confirmed the presence of canine distemper virus antigen in five of the dogs. Distemper had not been suspected from the clinical examination of the dogs.

Acute Disease↗

Human T-cell recognition of Epstein-Barr virus-induced replication antigen complexes.

Cellular immune responses to Epstein-Barr Virus (EBV)-associated antigens play an important role in the control of EBV-immortalized B lymphocytes. The nature of the antigens that serve as targets for these responses remains largely unknown. The purpose of the experiments reported here was to determine if virus-replication-associated antigens might function as targets for T-cell immunity with the emphasis on EBV-induced early antigen (EA) complex. Activated T-cell populations directed against this group of antigens would theoretically be effective in controlling the production of new virus progeny. Our results demonstrate that polypeptides associated with the EA complex do, in fact, induce the proliferation of memory T-cells from EBV-infected individuals irrespective of their serological status to the EA complex. The major polypeptide associated with the diffuse component of EA (EA-D) was notably effective in inducing a strong proliferative T-cell response. Cell lines established from EBV-infected individuals following continuous exposure to either p17 or p50 components of the EA complex over a 10- to 12-week period were composed primarily of CD4-positive T-cells, although CD8-positive cells also persisted for up to 9 weeks in culture. The data suggest that components of the EA complex might function as important target antigens in the immunosurveillance of EBV-infected cells.

Antigens, Viral↗

Sero-epidemiological investigations on human herpesvirus 6 (HHV-6) infections using a newly developed early antigen assay.

Monoclonal antibodies (MAbs) were developed against immunodominant HHV-6 (GS isolate) late and early proteins. The major late protein was identified as a probable glycoprotein with a molecular weight of approximately 110 kDa (gp 110). Immunoblotting of the early antigen yielded proteins of 41 and 38 kDa (p41/38). The MAb to the early protein reacted with cells infected with 14 different HHV-6 isolates. In contrast, the MAb against the late protein reacted with only 10 of these isolates, indicating that there was strain variation in this glycoprotein. The percentage of antibody-positive sera reactive with gp110 in the ELISA ranged from 56% to 96% among the different serum donor categories. In contrast, only 10-30% of the sera were positive for antibodies to p41/38 with the exception of sera from patients with African Burkitt's lymphoma (ABL) and Hodgkin's disease (HD). These antibody patterns denote the presence of active HHV-6 replication in patients with ABL and HD.

AIDS-Related Complex↗

Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats.

Naturally occurring transmissible spongiform encephalopathies have been recognised in sheep, man, mink, captive deer and cattle. Recently a similar disease was reported in a domestic cat. This paper describes the clinical and pathological findings in five cats with similar signs, including further observations on the original case. All the cats had a progressive, neurological disease involving locomotor disturbances, abnormal behaviour and, in most cases, altered sensory responses. Histopathological examination of the central nervous system revealed changes pathognomonic of the scrapie-like encephalopathies, including widespread vacuolation of the grey matter neuropil, vacuolation of neuronal perikarya and an astrocytic reaction.

Animals↗

Inflammatory middle ear disease of the dog: the clinical and pathological features of cholesteatoma, a complication of otitis media.

During a study of inflammatory middle ear disease in the dog cholesteatoma was found to accompany otitis media in seven of the 62 ears examined (11 per cent). The clinical, radiological and pathological findings in these animals imply that cholesteatoma in the dog is an aggressive lesion which must be differentiated from uncomplicated otitis media.

Animals↗

Inflammatory middle ear disease of the dog: the pathology of otitis media.

Inflammation within the middle ear cavity was recognised in 62 of the ears of 42 dogs with chronic otitis externa and otitis media, after biopsy or necropsy of the middle ear. The pathological changes in the middle ear resembled those reported in other species or after the experimental induction of otitis media in dogs. Perforations in the tympanic membrane were rarely found; on the contrary, the membrane was often thickened. However, the question of whether a perforation in the tympanic membrane must occur before otitis externa can extend to otitis media was not resolved.

Animals↗

Stress-related activation of Epstein-Barr virus.

Herpesviruses characteristically persist in a latent state in the body over the lifetime of an individual. Under certain conditions, any one of the herpesviruses can be reactivated. The mechanisms underlying the establishment of latent virus infection or viral reactivation are not well understood; however, it is known that the cellular immune response plays a very important role in the maintenance of latency and in virus reactivation. One of the factors thought to be associated with the reactivation of latent herpes-viruses is psychological stress. Using an examination stress model with medical student subjects, we previously demonstrated the reactivation of latent Epstein-Barr virus (EBV), as measured by increases in antibody titers. In this follow-up study using the same group of medical students, we found evidence for incomplete reactivation of latent EBV, with only selective expression of the latent virus genome.

Adult↗

Inhibition of Escherichia coli K12 by short-chain organic acids: lack of evidence for induction of the SOS response.

Sublethal concentrations of formic acid (10 mmol/l) and propionic acid (5 mmol/l) at pH 5.0 preferentially inhibit DNA synthesis and stop cell multiplication in the absence of a corresponding cessation in the increase of culture turbidity. The possibility that the acids induce the SOS response by starving cells of thymine or by causing physical damage to the DNA molecule has now been investigated. Accumulation of thymine into the cytoplasm of whole cells was not inhibited by either acid. Mutants defective in excision repair (uvr A6), recombination repair (rec A56) and polymerase activity (pol A1) were not more sensitive to the acids than their isogenic parent. No significant increase in cell length was observed from measurements of transmission electron microscope images of acid-treated cells. It is concluded, therefore, that sublethal concentrations of formic and propionic acid inhibit DNA synthesis without physically damaging DNA molecule, or starving the cell of essential thymine or otherwise inducing an SOS response.

DNA Repair↗

Short-chain organic acids at ph 5.0 kill Escherichia coli and Salmonella spp. without causing membrane perturbation.

When strains of Escherichia coli K12 and Salmonella spp. were incubated with 0.5-0.7 mol/l formic or propionic acid at pH 5.0, propionic acid was more active than formic acid. It killed 90% of the cell population within 60 min compared with over 3 h for formic acid. Cell death was not associated with a reduction in culture turbidity or a loss of membrane integrity since morphologically normal membranes were observed by electron microscopy and only a small proportion of the cytoplasmic enzyme beta-galactosidase leaked into the supernatant fluid of acid-treated E. coli K12 cultures.

Cell Membrane↗