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Biomedical subjects

G E Smith

Publications and source records attributed to G E Smith.

At least 19 recordsLinked to original sources
PubMed1992

Immunization with soluble protein-pulsed spleen cells induces class I-restricted cytotoxic T lymphocytes that recognize immunodominant epitopic peptides from Plasmodium falciparum and HIV-1.

CTL lines specific for two different proteins derived from the human pathogens, Plasmodium falciparum (malaria) circumsporozoite protein and HIV-1 reverse transcriptase, were obtained by immunizing mice with protein-pulsed syngeneic spleen cells. The lysis of the target cells was dependent on a class I MHC molecule and the accessory molecule CD8. Immunodominant epitopic peptides were identified previously in the two proteins using murine CTL derived after immunization with recombinant virus or sporozoites, or using CTL from HIV-1-infected patients. These peptides were also recognized by the CTL lines obtained after protein-pulsed spleen-cell immunization. A new CTL antigenic determinant was localized in HIV-1 reverse transcriptase to residues 514 to 528, a sequence that, if folded as an alpha-helix, would be strongly amphipathic. The determinant was tentatively narrowed, using overlapping peptides, to a core of at least nine residues, 515 to 523. This site was also recognized by CTL obtained by the two different methods of immunization. Therefore, extracellular proteins incubated with spleen cells can be processed and presented in vivo in the same way as intracellular proteins, resulting in recognition of the same epitopes in association with the same class I MHC molecules. The potential implications for vaccine development and for the understanding of class I-restricted Ag presentation are discussed.

Amino Acid Sequence↗
PubMed1992

Mechanical trauma as a risk factor in classic amyotrophic lateral sclerosis: lack of epidemiologic evidence.

We have examined the relationship between mechanical injuries and the subsequent development of classic amyotrophic lateral sclerosis (ALS) through a critical review of the literature. Only prospective evaluation of a large cohort of trauma victims can provide an unbiased answer to this controversy. However, such an evaluation would be prohibitively expensive, and the results would not be available in our lifetime. The results of retrospective case-control studies are conflicting in part because of biases in the selection of patients and controls, poor definition of the nature and extent of the trauma and its chronological relationship to the onset of ALS, and a non-uniform approach to the collection of antecedent information. More rigorously designed studies show no association of ALS to antecedent trauma. The existing data thus do not suggest that mechanical trauma is a risk factor for ALS. Future case-control studies should conform to a standardized methodology. The critical analysis presented here of the research on the purported connection between mechanical injury and ALS may serve as a model for the evaluation of the role of trauma in other chronic diseases. Application of these methodological principles may bring increased scientific rigor to assessing the frequently litigated question of what constitutes a true trauma sequela.

Adult↗
PubMed1992

Validity of the construct of nonverbal memory: a factor-analytic study in a normal elderly sample.

One problem in evaluating the construct of nonverbal memory is finding a purely nonverbal memory measure. Encouraged by initial research with a new measure, the Visual Spatial Learning Test (VSLT), we examined nonverbal memory in a normal elderly sample. Subjects were 460 community-dwelling individuals between the ages of 55-95. All received neuropsychological batteries which included the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised, the Rey Auditory Verbal Learning Test, and the VSLT. Two variable sets were created to avoid overlapping immediate and delayed recall trials for the same stimulus materials. Exploratory factor analyses using two different extraction methods were performed. Across analyses a single general memory factor was observed, no modality or time specific factors were found. If it can be assumed that we used adequate measures of nonverbal memory, our results combine with prior research to challenge the validity of the construct of nonverbal memory as distinct from verbal memory, especially in older normal adult populations.

Aged↗
PubMed1991

In vitro isolation of Cowdria ruminantium from plasma of infected ruminants.

A new and simple technique for isolation of C. ruminantium in bovine and ovine vascular endothelial cells (aorta, pulmonary artery) is described. Unlike previous studies, no efforts were made to retard cell growth by irradiation or chemicals. Instead, heparin-derived plasma samples obtained from only those animals exhibiting prolonged or extremely high temperatures were used. In this way, C. ruminantium was isolated from 27 of 37 samples (73%) and from 22 of 26 animals (85%). A total of six Zimbabwean stocks of C. ruminantium were isolated in cell culture.

Animals↗
PubMed1991

The short test of mental status. Correlations with standardized psychometric testing.

The Short Test of Mental Status can be administered to patients in inpatient and outpatient settings in approximately 5 minutes, and it contains items that test orientation, attention, immediate recall, arithmetic, abstraction, construction, information, and delayed (approximately 3 minutes) recall. The test was administered to a group of demented community patients and their age- and sex-matched control subjects. Using an age-adjusted approach, sensitivity of the test to identifying dementia is 86.4, with a specificity of 93.5. The test was compared with standardized tests of cognitive function such as the Wechsler Adult Intelligence Scale, Mattis Dementia Scale, and the Auditory Verbal Learning Test, and showed a high degree of correlation. Group means and standard deviations for subtest items and total score are presented for control subjects (n = 138), demented patients (n = 130), and patients with memory impairment only (n = 20). Percentile scores for subtest items in control subjects are also provided.

Aged↗
PubMed1991

A predominant group-specific neutralizing epitope of human immunodeficiency virus type 1 maps to residues 342 to 511 of the envelope glycoprotein gp120.

Recombinant native human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins gp160 and gp120 (residues 1 to 511) expressed in insect cells quantitatively adsorbed the group-specific neutralizing antibodies found in human sera. However, these antibodies were not adsorbed by envelope fragment 1 to 471 or 472 to 857 or by both fragments sequentially, even though together they add up to the full-length gp160 sequence. A hybrid envelope glycoprotein was constructed with residues 342 to 511 of the HIV-1 sequence and residues 1 to 399 of the simian immunodeficiency virus type 1 sequence to vary the HIV-1 sequence while preserving its conformation. This hybrid glycoprotein quantitatively adsorbed human neutralizing antibodies, while native simian immunodeficiency virus type 1 envelope glycoprotein did not. These results identify a new neutralizing epitope that depends on conformation and maps to residues 342 to 511 of gp120. It overlaps the extended CD4-binding site but is distinct from the V3 loop described previously (K. Javaherian et al., Proc. Natl. Acad. Sci. USA 86:6768-6772, 1989; J. R. Rusche et al., Proc. Natl. Acad. Sci. USA 85:3198-3202). Since it is conserved among diverse HIV-1 isolates, this new epitope may be a suitable target for future vaccine development.

Amino Acid Sequence↗
PubMed1990

Induction of CD4+ human cytolytic T cells specific for HIV-infected cells by a gp160 subunit vaccine.

Cytolytic T lymphocyte (CTL) responses were evaluated in humans immunized with recombinant human immunodeficiency virus type 1 (HIV) envelope glycoprotein gp160. Some vaccinees had gp160-specific CTLs that were shown by cloning to be CD4+. Although induced by exogenous antigen, most gp160-specific CTL clones also recognized gp160 synthesized endogenously in target cells. These clones lysed autologous CD4+ T lymphoblasts infected with HIV. Of particular interest were certain vaccine-induced clones that lysed HIV-infected cells, recognized gp160 from diverse HIV isolates, and did not participate in "innocent bystander" killing of noninfected CD4+ T cells that had bound gp120.

Cells, Cultured↗
PubMed1990

Evidence implicating MHC genes in the immunological nonresponsiveness to the Plasmodium falciparum CS protein.

The circumsporozoite (CS) protein is a major candidate vaccine antigen for the sporozoite stage of malaria. Both cytotoxic T cells (CTL) and antibody specific for the CS protein are thought to be important in protection. By examining the immune response in mice and humans we have shown that genes mapping to the major histocompatibility complex (MHC) are important for immune responsiveness. F1 mice between high antibody responders and low antibody responders are high antibody responders, suggesting that in this model immune suppressor genes do not control the immune response. Using synthetic peptides to map epitopes for CTL and helper T cells (which are important for the antibody response) we have shown that the T-cell epitopes are located in the polymorphic region of the protein, and we hypothesize that T cells have indeed selected the variation observed in the CS protein. The success of subunit vaccines will depend on the pattern of variation in different geographical locations, the ability to construct multivalent vaccines containing different variant epitopes from this protein, and on the existence of other sporozoite and liver-stage proteins involved in protection.

Animals↗
PubMed1989

Human immunodeficiency virus 1. Predominance of a group-specific neutralizing epitope that persists despite genetic variation.

HIV-1 is known to show a high degree of genetic diversity, which may have major implications for disease pathogenesis and prevention. If every divergent isolate represented a distinct serotype, then effective vaccination might be impossible. However, using a sensitive new plaque-forming assay for HIV-1, we have found that most infected patients make neutralizing antibodies, predominantly to a group-specific epitope shared among three highly divergent isolates. This epitope persists among divergent isolates and rarely mutates, despite the rapid overall mutation rate of HIV-1, suggesting that it may participate in an essential viral function. These findings, plus the rarity of reinfections among these patients, suggest that HIV-1 may be more susceptible to a vaccine strategy based on a group-specific neutralizing epitope than was previously suspected.

CD4 Antigens↗
PubMed1979

Autographa californica nuclear polyhedrosis virus structural proteins compared from in vivo and in vitro sources.

Polyhedrin obtained from Autographa californica nuclear polyhedrosis virus (AcMNPV) was apparently not modified in terms of primary structure after passage through alternate host systems, both in vivo and in vitro, as investigated by two-dimensional, high-voltage electrophoresis of tryptic digests of this protein as well as amino acid analysis. N-terminal analyses were conducted using an improved technique which showed proline to be the N-terminal amino acid. In addition, passage of enveloped nucleocapsids through alternate hosts as studied by SDS-PAGE showed the polypeptide compositions to be very similar.

Amino Acids↗
PubMed1976

Comparative metabolic studies of phenacetin and structurally-related compounds in the rat.

1. A comparative study of the metabolism of [acetyl-14C]phenacetin, [acetyl-14C]methacetin, [acetyl-14C]paracetamol and [acetyl=14C]acetanilide in the rat is reported. 2. The extent of N-deacetylation, evidenced by the measurement of respired 14CO2, varied, being greatest with acetanilide (25-31%) and least with paracetamol (6%). 3. The major urinary metabolites in each case were N-acetyl-p-aminophenyl sulphate and N-acetyl-p-aminophenyl glucuronide; the relative proportions varied with the sex of the animals and as a result of extended dosage. 4. The metabolism of [ethyl-14C]phenacetin and [ethyl-14C]phenetidine was investigated and the extent of O-dealkylation determined by measurement of respired 14CO2. 5. The metabolic pathways of some related glycolanilides and oxanilic acids included N-deacylation, and in the glycolanilides, oxidation of the glycollic group.

Acetaminophen↗