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Biomedical subjects

R Purcell

Publications and source records attributed to R Purcell.

At least 19 recordsLinked to original sources

Human class I supertypes and CTL repertoires extend to chimpanzees.

Using an in vitro peptide stimulation strategy, two chimpanzees that were acutely infected by the hepatitis B virus (HBV) produced peripheral blood CTL responses to several HBV-encoded epitopes that are known to be recognized by class I-restricted CTL in acutely infected humans. One animal responded to three HBV peptides that, in humans, are restricted by HLA-A2; the other animal responded to three peptides that are restricted by HLA-B35 and HLA-B51, members of the HLA-B7 supertype in man. The peptides recognized by each chimp corresponded with the ability of its class I molecules to bind peptides containing the HLA-A2 and HLA-B7 supermotifs. Similar, apparently class I-restricted CTL responses to some of these peptides were also detected in occasional HBV-uninfected chimps. These results demonstrate that the CTL repertoire overlaps in humans and chimps and that the HLA-A2 and HLA-B7 supertypes extend to the chimpanzee. Based on these results, the immunogenicity and efficacy of vaccines designed to induce CTL responses to human HLA-restricted viral epitopes may be testable in chimpanzees.

Amino Acid Sequence

Cognitive deficits in obsessive-compulsive disorder on tests of frontal-striatal function.

BACKGROUND: Although neuropsychological and neuroimaging studies of obsessive-compulsive disorder (OCD) have implicated the frontal cortex and subcortical structures in the pathophysiology of the disorder, few studies have examined cognitive function in patients with OCD on tasks validated in the assessment of frontal lobe and subcortical dysfunction. METHODS: The accuracy and latency of executive and visual memory function was assessed in 23 nondepressed OCD patients and 23 normal healthy controls matched for age, sex, education, and estimated IQ. RESULTS: The patients with OCD performed within the normal range on tasks of short-term memory capacity, delay dependent visual memory, pattern recognition, attentional shifting, and planning ability; however, specific cognitive deficits related to spatial working memory, spatial recognition, and motor initiation and execution were observed in the patient group. These deficits were not correlated with aspects of the patients' intellectual functioning or comorbid psychological symptoms, suggesting that the impairments were related to the specific clinical features of OCD. CONCLUSIONS: Patients with OCD showed specific cognitive deficits on tasks of executive and visual memory function. The pattern of impaired performance in these patients was qualitatively similar to the performance of patients with frontal lobe excisions and subcortical pathology on the same test battery, suggesting that the underlying pathophysiology of the disorder could best be conceptualized as reflecting dysfunction of frontal-striatal systems.

Adult

Neuropsychological deficits in obsessive-compulsive disorder: a comparison with unipolar depression, panic disorder, and normal controls.

BACKGROUND: The neuropsychological dysfunction associated with obsessive-compulsive disorder (OCD) has similarities to the deficits reported in other affective or anxiety disorders. We directly compared cognitive function in patients with OCD with that in matched patients with unipolar depression and panic disorder and healthy control subjects to establish the specific nature of neuropsychological deficits in OCD. METHODS: Thirty patients with OCD, 30 patients with panic disorder, 20 patients with unipolar depression, and 30 controls completed a computerized neuropsychological battery that assessed the accuracy and latency of executive, visual memory, and attentional functions. RESULTS: The groups did not differ according to age, years of education, or estimated IQ. However, we found group differences in cognitive performance. The patients with OCD were impaired on measures of spatial working memory, spatial recognition, and motor initiation and execution. In contrast, performance of these tasks by patients with panic disorder or depression did not differ from that of controls. There were no group differences for performance on the measures of planning, cognitive speed, pattern recognition, and delayed matching to sample, although patients with depression were impaired for attentional set shifting. CONCLUSIONS: Neuropsychological deficits were observed in patients with OCD that were not observed in matched patients with panic disorder or unipolar depression. As such, the cognitive dysfunction in OCD appears to be related to the specific illness processes associated with the disorder.

Adult

The hepatitis C virus: overview.

Our knowledge of hepatitis C virus (HCV) dates only from 1975, when non-A, non-B hepatitis was first recognized. It was not until 1989 that the genome of the virus was first cloned and sequenced, and expressed viral antigens used to develop serological assays for screening and diagnosis. HCV is in a separate genus of the virus family Flaviviridae. It is a spherical enveloped virus of approximately 50 nm in diameter. Its genome is a single-stranded linear RNA molecule of positive sense and consists of a 5' noncoding region, a single large open reading frame, and a 3' noncoding region. The open reading frame encodes at least three structural and six nonstructural proteins. The genome is characterized by significant genetic heterogeneity, based on which HCV isolates can be classified into six major genotypes and more than 50 subtypes. Even individual isolates of HCV are genetically heterogeneous (quasispecies diversity). Genetic heterogeneity of HCV is greatest in the amino-terminal end of the second envelope protein (hypervariable region 1). This region may represent a neutralization epitope that is under selective pressure from the host's humoral immune response. Infection with HCV proceeds to chronicity in more than 80% of cases, and even recovery does not protect against subsequent re-exposure to the virus. The development of a broadly protective vaccine against HCV will therefore require a better understanding of the molecular biology and immune response to this virus.

Animals

Powered functional endoscopic sinus surgery.

The use of powered instrumentation in functional endoscopic sinus surgery has been a revolutionary development in the surgical treatment of chronic sinusitis. Several studies have demonstrated the safety, efficacy, and ease of use of this new technique. To provide support and coordinate the surgical process in powered functional endoscopic sinus surgery procedures, perioperative nurses must have an appreciation for its specific equipment handling and for appropriate patient care. This article describes a specific protocol that perioperative nurses can use to facilitate efficient and safe surgical environments for patients who undergo powered endoscopic sinus surgery procedures.

Chronic Disease

Neuropsychological function in young patients with unipolar major depression.

BACKGROUND: While neuropsychological studies have consistently reported impaired cognition in elderly patients with unipolar depression, studies of cognitive function in younger patients with depression have produced equivocal results. The aim of this study was to examine the presence and nature of cognitive deficits in young patients with depression. METHODS: Neuropsychological function was assessed in 20 young patients with unipolar depression, in comparison to 20 age-, education- and IQ- matched controls. Subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were employed, as this battery has proved sensitive to deficits in middle-aged and elderly patients with depression. RESULTS: The patients were not impaired for short-term memory capacity, spatial working memory, planning ability, cognitive speed, delayed matching to sample or recognition memory. Compared to controls, the patients showed impaired subsequent movement latencies on the Tower of London task, suggesting deficits in the ability to sustain motor responses in depression. The depression group were also impaired on the task of attentional set shifting, requiring more trials to criterion at the intradimensional stage of the task and being more likely to fail the task at the extradimensional shift stage than controls. Further analysis indicated that half of the depression group failed to complete all stages of the set shifting task. These patients were more likely to have required in-patient hospitalization at some time during their illness. CONCLUSIONS: These results indicate that there are specific cognitive deficits in young patients with depression and that their presence may be related to a history of hospitalization.

Adolescent

Acute viral hepatitis in Saudi Arabia: seroepidemiological analysis, risk factors, clinical manifestations, and evidence for a sixth hepatitis agent.

We conducted a prospective, descriptive cohort study of all 217 cases of acute viral hepatitis (AVH) seen in adults during 1992 at the sole hospitals with infectious disease departments in the second and third largest cities in the Kingdom of Saudi Arabia. In addition, we undertook a nested case-control study. Our goals were (1) to determine the causes, demographics, risk factors, and clinical characteristics of AVH in the Kingdom; (2) to evaluate the reliability of diagnostic tests for acute hepatitis C and E; and (3) to assess the relative importance, characteristics, and risk factors of a sixth hepatitis agent, non-A-E. All cases and controls completed a questionnaire. Cases provided blood samples for studies of serum bilirubin, alanine and aspartate aminotransferases, and antibody to hepatitis viruses as well as genome detection studies. The results of serological and molecular tests were used to categorize each case as hepatitis A, B, C, D, E, or non-A-E. Historical, clinical, and laboratory determinants were statistically analyzed by comparisons between groups with different types of AVH and controls. Analysis of risk factors suggested that hepatitis C and D were parenterally transmitted, while hepatitis A, E, and non-A-E were not; the route of transmission of hepatitis B was unclear. Hepatitis E was strongly associated with living or traveling on the Indian subcontinent. The clinical disease caused by all six agents was indistinguishable. The putative sixth agent caused 13% of cases. The second-generation tests for antibody to HCV and HEV were relatively reliable for the diagnosis of AVH.

Acute Disease

Structural and functional characterization of human immunodeficiency virus tat protein.

Site-directed mutagenesis was used to identify functional domains present within the human immunodeficiency virus (HIV) tat protein. Transient cotransfection experiments showed that derivatives of tat protein with amino acid substitutions either at the amino-terminal end or at cysteine residue 22, 37, 27, or 25 were no longer able to transactivate HIV long terminal repeat-directed gene expression. Incubation of Tat expressed in Escherichia coli with zinc demonstrated that both authentic Tat and cysteine mutation derivatives could form metal-protein complexes. The tat proteins that contained alterations within the cluster of positively charged amino acid residues retained their ability to transactivate gene expression, albeit at markedly reduced levels. Indirect immunofluorescence showed that the authentic tat protein and the amino-terminal and cysteine substitution mutants all localized in the nucleus, with accumulation being most evident in the nucleolus. In contrast, nuclear accumulation was greatly reduced with the basic-substitution mutations. Consistent with this result, a fusion protein that contained amino acids GRKKR, derived from the basic region, fused to the amino-terminal end of beta-galactosidase also accumulated within the nucleus. These results demonstrate that the 14-kilodalton tat protein contains at least three distinct functional domains affecting localization and transactivation.

Amino Acid Sequence

Genetic relatedness among animal rotaviruses.

The genomic relatedness among representative rotavirus strains was examined by employing cross-hybridization techniques. Single stranded (ss) RNA prepared by in vitro transcription of purified rotavirus particles and labeled with either 32P or 125I was hybridized to denatured genomic, double stranded (ds) RNAs. The hybrids formed were analyzed by polyacrylamide gel electrophoresis (PAGE) or by testing their sensitivity to digestion with single strand specific nuclease (S-1 nuclease). A relatively high degree of genomic homology was found to exist among several bovine rotavirus strains obtained from different geographical areas. Similarly, a high degree of homology was found between two different simian rotavirus strains, and also between two porcine strains. The human Wa strain exhibited a low degree of genomic homology with simian, bovine and canine strains whereas a higher level of homology was detected between the human Wa strain and the porcine strains. The observed RNA sequence divergences of rotaviruses isolated from different animal species are in agreement with the restricted host range of these viruses and their known antigenic differences and suggest a divergent evolution of their genomes.

Animals

Genetic relatedness among human rotaviruses.

The genetic relatedness of 81 clinical rotavirus isolates to the human rotavirus prototype strains Wa (subgroup 2, serotype 1) and DS-1 (subgroup 1, serotype 2) was examined by RNA hybridization techniques. Labeled single-stranded (+) transcripts of Wa or DS-1 virus were incubated with denatured genomic rotaviral RNAs, and the resulting hybrids were subjected to gel electrophoresis and autoradiography. Nineteen of the specimens contained subgroup 1 rotavirus with a "short" RNA migration pattern. These viruses were found to be closely related to the DS-1 strain and were associated with illness of short duration. The remaining 62 isolates belonged to subgroup 2 and exhibited a "long" RNA migration pattern. Fifty-four of these isolates exhibited significant hybridization with the Wa strain probe. Four isolates yielded multiple hybrid bands with the Wa probe but also possessed at least one gene segment homologous to the DS-1 strain. The remaining four subgroup 2 rotaviruses did not exhibit significant homology in the form of labeled hybrid bands when tested with either the Wa or DS-1 probe. These findings suggest that most clinical rotavirus isolates belong to one of two human rotavirus "families" defined as Wa-like or DS-1-like. Our observations also suggest that reassortment occurs in vivo between rotaviruses belonging to the two human rotavirus "families" and that there are one or more additional families of human rotavirus.

Genes, Viral

Complexes of hepatitis B surface antigen and immunoglobulin M in the sera of patients with hepatitis B virus infection.

Hepatitis B surface antigen (HBsAg) bound to immunoglobulin M (IgM) was detected in sera of HBsAg carriers by a radioimmunoassay based on selective absorption of the immunoglobulin on a solid phase coated with antiserum to human IgM. Isopycnic banding and rate-zonal sedimentation have shown that the reaction is related to particulate forms of the HBsAg complexed with IgM. The binding of IgM possibly occurred because of a selective affinity of these molecules to the surface of HBsAg particles. HBsAg/IgM was found transiently in 24 of 25 (96%) patients with acute self-limited hepatitis B and persistently in 6 of 25 patients whose acute hepatitis B progressed to chronicity. It was also found in 20 of 39 (51%) chronic HBsAg carriers with inactive and asymptomatic infection. The HBsAg/IgM phenomenon is not dependent on replication of hepatitis B virions; its persistence in patients with acute hepatitis B may provide complementary evidence of transition of the infection to chronicity.

Animals