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Biomedical subjects

K Parker

Publications and source records attributed to K Parker.

At least 91 records · Page 5Linked to original sources
PubMed1987

Immunological cross-reactivity between preS2 sequences of the hepatitis B virus envelope proteins corresponding to serological subtypes adw2 and ayw.

An immune response to epitopes localized on the preS region of the hepatitis B virus (HBV) envelope (env) is elicited during recovery from HBV infection and appears to play a role in virus clearance. Anti-preS antibodies (Ab) are expected to be protective against HBV infection as indicated by the virus-neutralizing capacity of Ab to a preS2-specific synthetic peptide preS(120-145). However, there is considerable amino acid variability between preS regions corresponding to distinct serological subtypes of HBV, raising the question whether the preS sequences are sufficiently related immunologically to have the potential of inducing cross-protective immunity. To answer this question concerning the preS2 region, antisera to synthetic peptides preS(120-153) and preS(128-153) corresponding to subtypes adw2 and ayw, as well as to the native env [ayw] protein were raised. Using the resulting polyclonal Ab, an immunological relatedness between preS2 sequences of subtypes adw2 and ayw was demonstrated. On the other hand, Ab selected by affinity chromatography or by cloning hybridoma cells may recognize with strong preference subtype-specific determinants within the preS2 region when the compared antigens are in solution rather than on the solid phase. These findings have implication for the design of: (1) preS2-specific immunogens and (2) immunoassays for quantitation of preS2 sequences in HBV env proteins.

Amino Acid Sequence↗
PubMed1987

Diphtheria toxin receptor binding domain substitution with interleukin-2: genetic construction and properties of a diphtheria toxin-related interleukin-2 fusion protein.

We have genetically replaced the diphtheria toxin receptor binding domain with a synthetic gene encoding interleukin-2 (IL-2) and a translational stop signal. The diphtheria toxin-related T-cell growth factor fusion gene encodes a 70 586-d polypeptide, pro-IL-2-toxin. The mature form of IL-2-toxin has a deduced mol. wt of 68,086 and is shown to be exported to the periplasmic compartment of Escherichia coli (pABI508), and contain immunologic determinants intrinsic to both its diphtheria toxin and IL-2 components. IL-2-toxin has been purified from periplasmic extracts of recombinant strains of E. coli (pABI508) by immunoaffinity chromatography using immobilized anti-IL-2. The purified chimeric toxin is shown to selectively inhibit protein synthesis in IL-2 receptor bearing targeted cells, whereas cell lines which do not express the IL-2 receptor are resistant to IL-2-toxin action.

Bacterial Proteins↗
PubMed1987

Genetic assembly and selective toxicity of diphtheria-toxin-related polypeptide hormone fusion proteins.

The reports of Miyanohara et al. (1986) and Murphy et al. (1986) were the first to describe the genetic construction, expression, and receptor-specific selective toxicity of a chimaeric toxin. In the present report, we have extended these earlier observations and have shown that the fusion of a modified gene encoding IL-2 to a truncated diphtheria toxin gene also results in the expression of a biologically active chimaeric IL-2 toxin. In both instances we have used receptor-binding-domain substitution and have genetically coupled those portions of the diphtheria toxin structural gene that encode the ADP-ribosyl transferase activity of fragment A and lipid-associating domains of fragment B to modified genes which encode either the polypeptide hormone alpha-MSH or the T-cell growth factor IL-2. The chimaeric toxins expressed from these gene fusions have been shown to be selectively targeted to those eukaryotic cells that carry specific surface receptors for the ligand compounds of the hybrid. For example, in the case of the IL-2 toxin, it is clear that the selective action of this hybrid protein is based upon both its diphtheria-toxin and IL-2-related components. Following binding to the IL-2R on activated and/or malignant T-cell, IL-2 toxin is internalized by receptor-mediated endocytosis. Upon acidification of the endosome, diphtheria toxin fragment B portions of the chimaeric toxin facilitate the delivery of fragment A to the cytosol where it catalyses the ADP ribosylation of EF-2. The assembly of chimaeric toxins at the level of the gene offers several advantages over chemical linkage. Since chemical linkage of the toxophore and ligand components of the conjugate toxins requires activation of the epsilon-amino moiety of lysine residues with reagents that will allow for subsequent disulphide linkage, the precise site of coupling is generally not known. In addition, there has been considerable concern over the lability of the disulphide bond between the toxophore and ligand components in vivo due to the action of disulphide reductases. The assembly of chimaeric toxins at the level of the gene allows for precise linkage of the toxophore and ligand components. Since the linkage between the toxophore and ligand is a peptide bond, the chimaeric toxin should be stable in vivo. In addition, the genetic construction of chimaeric toxins also allows for further protein engineering through site-directed mutagenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1986

Identification and chemical synthesis of a host cell receptor binding site on hepatitis B virus.

Hepatitis B virus (HBV) has not yet been propagated in vitro, and knowledge concerning its reaction with receptors on target cells remained scant. We have located within the HBV envelope proteins a sequence mediating the attachment of HBV to human hepatoma HepG2 cells. A synthetic peptide analog (PLGFFPDHQLDPAFGANSNNPDWDFNP) is recognized by both cell receptors and anti-HBV antibodies and elicits antibodies reacting with native HBV. The synthetic peptide is a promising immunogen expected to elicit protective antibodies based on the concept of the attachment blockade pathway of virus neutralization. The approach described here, based on anti-peptide antisera and the binding of peptide analogs to cell receptors is generally applicable for the delineation of cell receptor binding sites on viruses with known gene sequences.

Amino Acid Sequence↗
PubMed1986

Pituitary hormone response to cigarette smoking.

Nausea was induced by having subjects smoke two high nicotine cigarettes in quick succession. Plasma levels of prolactin, adrenocorticotropic hormone, beta-endorphin/beta-lipotropin, growth hormone, arginine vasopressin, and neurophysin I increased without changes in thyroid stimulating hormone, luteinizing hormone, or follicle stimulating hormone. Nausea and pituitary hormone release correlated with high nicotine intake (smoking 2.87 mg nicotine cigarettes) but did not occur during lower nicotine intake (smoking 0.48 mg nicotine cigarettes). Individual differences in nausea and related hormonal responses may provide an objective method for predicting receptivity to smoking.

Adult↗
PubMed1986

Characterization of monoclonal antibodies specific for the pre-S2 region of the hepatitis B virus envelope protein.

Monoclonal antibodies (McAb) specific for the pre-S region of the hepatitis B virus (HBV) envelope protein were prepared using HBV particles of hepatitis B surface antigens (HBsAg) as immunogens. The antibodies reacted in Western blot analyses and in ELISA with pre-S2 sequences of the HBV envelope protein. Pepsin or protease V8 treatment of the antigen abolished reactivity. The fine specificity of one of the McAb (F376) was established by immunoassays using synthetic peptides and a pre-S2-beta-galactosidase fusion protein expressed in E. coli. The shortest peptide recognized by F376 is demarcated by residues pre-S(132) at the N-terminal and pre-S(140)-pre-S(145) at the C-terminal. The corresponding amino acid sequence (for HBV subtype adw2) is: QDPRVRGLY(LPAGG). Additional amino acid residues at the N-terminal, and possibly at the C-terminal ends contribute to the binding of McAb, probably due to conformational influences. The McAb was applied to immunoassays of pre-S2 sequences in purified HBsAg and in human sera containing HBsAg.

Antibodies, Monoclonal↗
PubMed1986

Antibodies to a synthetic peptide from the preS 120-145 region of the hepatitis B virus envelope are virus neutralizing.

Studies with synthetic peptides have provided evidence for the presence of preS coded sequences in the envelope (env) proteins of hepatitis B virus (HBV) and indicated that these sequences are involved in the specific attachment of HBV to liver cells. Scanning of the preS sequence for immunodominant continuous epitopes identifies the sequence within residues preS (120-145) as the most immunogenic in eliciting antibodies recognizing HBV and as the most efficiently binding antibodies from sera of rabbits and humans immunized with HBV env proteins. To assess the potential of preS (120-145) as a synthetic vaccine against hepatitis B, in vitro neutralization of the virus by rabbit antiserum to the peptide was assayed in chimpanzees. The animals, subsequently proven to be susceptible to HBV infection, did not develop hepatitis B as judged by negative serological tests for HBV-associated antigens and antibodies and by normal serum alanine aminotransferase levels and normal liver biopsies. These results establish the role of preS domains in the process of virus neutralization and the potential of synthetic preS analogues for hepatitis B vaccination.

Animals↗
PubMed1986

Neuromuscular electrical stimulation of the muscles surrounding the shoulder.

Neuromuscular electrical stimulation (NMES) can be used to augment range-of-motion, strengthening, and facilitation treatment programs of the muscles surrounding the shoulder. The purposes of this article are 1) to describe the uses of NMES around the shoulder joint as developed through our clinical use and 2) to detail the effects of an NMES program on chronic shoulder subluxation as determined by a clinical study. Because of the complexities of this multiarticular joint, NMES is most useful in the initial phase of the ROM, and stimulated contractions are compromised, relatively, as the humerus moves above the 90-degree horizontal plane. The use of NMES to provide scapular stabilization often entails unwanted alteration of the pressures on the spinal column, occasionally making the treatment program unusable. Electrical stimulation to prevent or correct shoulder subluxation, especially in the neurologically involved patient, provides the therapist with a powerful new treatment technique. In a group of stroke patients, shoulder subluxation was reduced significantly (p less than .05) at the completion of a six-week NMES program. Some of the problems, and possible solutions, unique to the development of electrical stimulation programs for the shoulder muscles are discussed.

Adult↗
PubMed1985

Helping school-age children cope with Tourette syndrome.

Tourette Syndrome, a neurological "tic" disorder characterized by involuntary muscular movements and vocal sounds, can be psychologically devastating and unbearable for the school-age child. Through the help and support of educational and medical professionals, children and their families can learn to accept and cope with the uncontrollable, bizarre behavior of the Tourette Syndrome.

Adaptation, Psychological↗
PubMed1984

The effects of smoking on ACTH and cortisol secretion.

The relationship among changes in plasma nicotine, ACTH, and cortisol secretion after smoking were investigated. Ten male subjects smoked cigarettes containing 2.87 mg nicotine and 0.48 mg nicotine. No rises in cortisol or ACTH were detected after smoking 0.48 mg nicotine cigarettes. Cortisol rises were significant in 11 of 15 instances after smoking 2.87 mg nicotine cigarettes, but ACTH rose significantly in only 5 of the 11 instances where cortisol increased. Each ACTH rise occurred in a subject who reported nausea and was observed to be pale, sweaty, and tachycardic. Peak plasma nicotine concentrations were not significantly different in sessions when cortisol rose with or without ACTH increases, but cortisol increases were significantly greater in nauseated than in non-nauseated smokers. Our data suggest that smoking-induced nausea stimulates cortisol release by stimulating ACTH secretion and that cortisol secretion in non-nauseated smokers may occur through a non-ACTH mechanism. It is not clear whether nicotine or some other stimulus inherent in smoking is responsible for cortisol secretion without ACTH secretion.

Adrenocorticotropic Hormone↗
PubMed1984

Cigarette smoking as a risk for cardiovascular disease V: Biochemical parameters with increased and decreased nicotine content cigarettes.

Cigarette smokers were assessed for customary smoking behavior and then were assigned a cigarette which was 0.4 mg higher or lower in nicotine and after 4 weeks, were returned to their customary brand. Biochemical indices of smoking behavior including blood carboxyhemoglobin (COHb), plasma nicotine, cotinine and thiocyanate (-SCN) were measured every 2 weeks. When nicotine availability was increased, smokers received an increased nicotine bolus per puff as determined by plasma nicotine and did not alter smoking topography or cigarettes per day. Over the 4 weeks, plasma cotinine increased without corresponding increases in COHb and -SCN. The return to standard brand resulted in declining cotinine levels but increasing COHb and -SCN, suggesting altered inhalation patterns. In smokers switched to a low yield cigarette, there was a decrease in the nicotine obtained per cigarette followed by a steady rise in plasma cotinine, -SCN and blood COHb over the 4-week period. A positive correlation was observed between cotinine and the gas phase constituents during the change to lower yield and back to standard brand cigarettes. These results indicate that cigarette smokers compensate for decreased nicotine yield with concomitant increases in gas phase components. In addition, increased nicotine availability results in an increased body burden of nicotine and "tar," but not gas phase constituents. The relative risks of cardiovascular disease under these two situations, which increase exposure to nicotine or gas phase components, deserve careful consideration.

Adult↗
PubMed1984

Patterns of preweaning diarrhea in piglets on a central California ranch.

To determine risk factors for development of diarrhea in litters of preweaned piglets, data were analyzed from records of 4,397 litters of swine farrowed on a central California ranch 1978-1982. Sixty-four percent of litters were treated for diarrhea. Statistical analysis by multiple logistic regression showed that litters born to young sows (parity less than or equal to 2) were 1.7 times more likely to develop diarrhea before weaning than were litters born to older sows (parity greater than or equal to 3) and that litters born on one end of farrowing barns were 1.3 times more likely to develop diarrhea than were litters born in the other end. The association of diarrhea with other variables--dam breed, sire, gestation group, gestation length, size of litter, number of mummies, runts or stillbirths per litter, farrowing barn of birth or day of the week farrowed--was weak or nonexistent (P greater than 0.01).

Animals↗
PubMed1983

Neuromuscular electrical stimulation for the head-injured patient.

Recent research has shown that electrical stimulation is effective in treatment programs designed to maintain or gain range of motion, to facilitate voluntary motor control, and to strengthen muscles weakened by disuse. All of these treatment goals are relevant to the head-injured patient who frequently demonstrates profound disuse atrophy, joint contractures with excessive muscle tone, and decreased voluntary motor capabilities. As the cognitive status of the head-injured patient improves, electrical stimulation can be incorporated into traditional treatment programs to enhance their effectiveness. This article discusses using neuromuscular electrical stimulation with programs aimed at managing contractures, reducing spasticity, and facilitating voluntary motion. The limitations of electrical stimulation in the head-injured patient population are addressed.

Adult↗
PubMed1983

A meta-analysis of the reliability and validity of the Rorschach.

The results of a meta-analysis of Rorschach studies indicate that reliabilities in the order of .83 and higher and validity coefficients of .45 or .50 and higher can be expected for the Rorschach--when hypotheses supported by empirical or theoretical rationales are tested using reasonably powerful statistics. Three important determinants of variance accounted for in a variety of Rorschach scores were identified in 530 statistics from 39 papers published in the Journal of Personality Assessment from 1971 to 1980. The a priori theoretical or empirical evidence determining the likelihood of obtaining significant results, and the power of the statistic used to measure the results, as well as the interaction between the likelihood of results and the power of the statistic used, were all significant determinants of the proportion of variance accounted for in the Rorschach measures reported.

Journal Article↗