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Biomedical subjects

H Sampson

Publications and source records attributed to H Sampson.

At least 19 recordsLinked to original sources
PubMed2001

Variation in enzymes of arylamine procarcinogen biotransformation among bladder cancer patients and control subjects.

Arylamines such as 2-naphthylamine and 4-aminobiphenyl are suspected human bladder procarcinogens that require bioactivation to DNA-reactive species to exert their carcinogenic potential. The goals of the present study were (i) to assay for the presence of the arylamine acetyltransferases NAT1 and NAT2, and of the cytochrome P450 isoform CYP1A2, in human bladder epithelium; and (ii) to determine whether the activities of these arylamine biotransforming enzymes differ between bladder cancer patients and control subjects. We measured in-vitro enzyme activities in biopsies of normal, undiseased bladder epithelium obtained from 103 bladder cancer patients. NAT1 activity was detectable in all samples, with mean levels higher than those found in human liver. Kinetic evidence also suggested low levels of NAT2 expression in this tissue, but there was no detectable CYP1A2 by either enzymatic or immunochemical measurements. We also compared several probe drug indices of in-vivo NAT1, NAT2 and CYP1A2 activity between 53 bladder cancer patients and 96 cancer-free control subjects who were carefully matched for age, gender and smoking status. NAT1 and NAT2 genotypes were also determined. No significant differences were found between bladder cancer patients and control subjects for a number of individual phenotypic or genotypic predictors of enzyme function. Our results suggest that although expression of particular arylamine biotransforming enzymes within the bladder tissue could play a significant role in locally bioactivating arylamine procarcinogens in theory, interindividual variations in CYP1A2, NAT1 and NAT2 activities do not significantly differ between bladder cancer patients and control subjects when potential arylamine exposures are controlled for

Acetyltransferases↗
PubMed2000

Structure of the major peanut allergen Ara h 1 may protect IgE-binding epitopes from degradation.

In the past decade, there has been an increase in allergic reactions to peanut proteins, sometimes resulting in fatal anaphylaxis. The development of improved methods for diagnosis and treatment of peanut allergies requires a better understanding of the structure of the allergens. Ara h 1, a major peanut allergen belonging to the vicilin family of seed storage proteins, is recognized by serum IgE from >90% of peanut-allergic patients. In this communication, Ara h 1 was shown to form a highly stable homotrimer. Hydrophobic interactions were determined to be the main molecular force holding monomers together. A molecular model of the Ara h 1 trimer was constructed to view the stabilizing hydrophobic residues in the three dimensional structure. Hydrophobic amino acids that contribute to trimer formation are at the distal ends of the three dimensional structure where monomer-monomer contacts occur. Coincidentally, the majority of the IgE-binding epitopes are also located in this region, suggesting that they may be protected from digestion by the monomer-monomer contacts. On incubation of Ara h 1 with digestive enzymes, various protease-resistant fragments containing IgE-binding sites were identified. The highly stable nature of the Ara h 1 trimer, the presence of digestion resistant fragments, and the strategic location of the IgE-binding epitopes indicate that the quaternary structure of a protein may play a significant role in overall allergenicity.

Acids↗
PubMed1999

Information before coronial necropsy: how much should be available?

AIM: To assess the amount and quality of information supplied before undertaking a coroner's necropsy, based on the supposition that insufficient information may adversely affect the quality of the necropsy. METHODS: For a one year period (947 cases), sudden death reports from the coronial jurisdiction of South Yorkshire (West) were audited to assess the quality of information supplied. Seven specific items of information were sought: age, sex, occupation, date of death, location of the body, position of the body, date of last seeing a general practitioner, and relevant medical history. The results from necropsy and non-necropsy cases were compared. RESULTS: Only 22.1% of reports contained all seven items of information. There was no difference between the amount of information supplied in necropsy and non-necropsy cases except about when the general practitioner last saw the deceased. An occupational history was not available in 40.4% of all deaths. CONCLUSIONS: The quality of information supplied to the pathologist before necropsy may be suboptimal and could affect the thoroughness of the necropsy itself.

Autopsy↗
PubMed1998

Biochemical and structural analysis of the IgE binding sites on ara h1, an abundant and highly allergenic peanut protein.

Allergy to peanut is a significant IgE-mediated health problem because of the high prevalence, potential severity, and chronicity of the reaction. Ara h1, an abundant peanut protein, is recognized by serum IgE from >90% of peanut-sensitive individuals. It has been shown to belong to the vicilin family of seed storage proteins and to contain 23 linear IgE binding epitopes. In this communication, we have determined the critical amino acids within each of the IgE binding epitopes of Ara h1 that are important for immunoglobulin binding. Surprisingly, substitution of a single amino acid within each of the epitopes led to loss of IgE binding. In addition, hydrophobic residues appeared to be most critical for IgE binding. The position of each of the IgE binding epitopes on a homology-based molecular model of Ara h1 showed that they were clustered into two main regions, despite their more even distribution in the primary sequence. Finally, we have shown that Ara h1 forms a stable trimer by the use of a reproducible fluorescence assay. This information will be important in studies designed to reduce the risk of peanut-induced anaphylaxis by lowering the IgE binding capacity of the allergen.

Adult↗
PubMed1998

Cellular and molecular characterization of a major soybean allergen.

Soybean proteins share a large number of cross-reacting allergens with other members of the legume family; however, soy-allergic patients rarely react clinically to other members of the legume family. Gly m Bd 30K, an IgE-binding protein with a molecular weight of 30 kD, was identified in soybean extracts by Western IgE-immunoblot analysis. This monomeric allergen was shown to have an N-terminal amino acid sequence and amino acid composition identical to that of the seed 34-kD protein, P34, a thiol protease of the papain family. Electron-microscopic immunolocalization of P34 monoclonal antibodies and IgE binding to sections of soybean seeds showed dense staining throughout the vacuolar bodies, localizing the allergens in protein storage vacuoles of seed cotyledons. We used pooled serum from soybean-sensitive patients to determine the linear IgE-specific epitopes in the 34-kD allergen amino acid sequence. B-cell epitope mapping revealed 10 regions of IgE-binding activity using an overlapping peptide strategy of 15-mers offset by 8 amino acids throughout the P34 sequence. Smaller overlapping peptides, 10-mers offset by 2 amino acids, revealed 16 distinct linear epitopes, 9 of which were mapped to the mature protein. No obvious amino acid sequence motifs could be identified by the smaller IgE-binding epitopes. Using individual patient serum, 5 immunodominant epitopes were identified in this allergen.

Allergens↗
PubMed1997

Identification and mutational analysis of the immunodominant IgE binding epitopes of the major peanut allergen Ara h 2.

A major peanut allergen, Ara h 2, is recognized by serum IgE from > 90% of patients with peanut hypersensitivity. Biochemical characterization of this allergen indicates that it is a glycoprotein of approximately 17.5 kDa. Using N-terminal amino acid sequence data from purified Ara h 2, oligonucleotide primers were synthesized and used to identify a clone (741 bp) from a peanut cDNA library. This clone was capable of encoding a 17.5-kDa protein with homology to the conglutin family of seed storage proteins. The major linear immunoglobulin E (IgE)-binding epitopes of this allergen were mapped using overlapping peptides synthesized on an activated cellulose membrane and pooled serum IgE from 15 peanut-sensitive patients. Ten IgE-binding epitopes were identified, distributed throughout the length of the Ara h 2 protein. Sixty-three percent of the amino acids represented in the epitopes were either polar uncharged or apolar residues. In an effort to determine which, if any, of the 10 epitopes were recognized by the majority of patients with peanut hypersensitivity, each set of 10 peptides was probed individually with serum IgE from 10 different patients. All of the patient sera tested recognized multiple epitopes. Three epitopes (aa27-36, aa57-66, and aa65-74) were recognized by all patients tested. In addition, these three peptides bound more IgE than all the other epitopes combined, indicating that they are the immunodominant epitopes of the Ara h 2 protein. Mutational analysis of the Ara h 2 epitopes indicate that single amino acid changes result in loss of IgE binding. Two epitopes in region aa57-74 contained the amino acid sequence DPYSP that appears to be necessary for IgE binding. These results may allow for the design of improved diagnostic and therapeutic approaches to peanut hypersensitivity.

2S Albumins, Plant↗
PubMed1997

Interpersonal guilt: the development of a new measure.

We describe the development of a new measure to assess guilt related to concern about harming others. The two versions of the Interpersonal Guilt Questionnaire, a 45-item and 67-item version, include theoretically-based and clinically relevant categories of guilt: survivor guilt, separation/disloyalty guilt, omnipotent responsibility guilt, and self-hate guilt. Preliminary reliability and validity studies for both versions are presented, based on clinical and nonclinical samples of subjects. Subscales on both versions show good internal consistency; however, the second version, which expanded on the first, is more psychometrically sound overall. Both versions demonstrated predicted correlations with previously published measures of guilt and related affects, such as shame and depression, and with attributional style. Differences between clinical and nonclinical samples are reported and the relevance of survivor guilt and shame to psychopathology is noted.

Adult↗
PubMed1993

Food allergies in children.

Ingested food represents the greatest foreign antigenic load that confronts the human immune system. In most individuals tolerance develops to food antigens that are continually gaining access to the body. When tolerance fails to develop, the immune system may react with a hypersensitivity reaction. Allergies to food affect up to 8% of children less than 3 years of age and 1% to 2% of the general population. Symptoms include the gastrointestinal, cutaneous, and respiratory symptoms, as well as systemic anaphylaxis with shock. Clinical investigations in the past have characterized the food hypersensitivity disorders, but our understanding of the basic immunopathologic mechanism remains incomplete. Current progress in allergen characterization and the rigorous scientific methods now being applied to this field by many investigators provide hope that new information regarding the pathogenesis of these disorders and new forms of therapy will soon become available. For now, practicing physicians must carefully diagnose specific food sensitivities and educate patients and their families in the elimination of the responsible food allergen.

Adolescent↗
PubMed1981

Familial hypogammaglobulinemia with variable serum immunoglobulins. Concordance with lymphocyte ecto-5'-nucleotidase deficiency.

Four male subjects from two generations of a black family were found to have variable expression of hypogammaglobulinemia (IgG, IgM, and IgA deficiency in two, IgA deficiency in one, and IgM and IgA deficiency in another) and also to be moderately deficient in the lymphocyte plasma membrane enzyme, 5'-nucleotidase. The inheritance pattern of the immune abnormality is compatible with X linkage. The affected patients had normal numbers of complement receptor-bearing lymphocytes, variably depressed proportions of IgM- and IgD-bearing lymphocytes, and impaired ability to synthesize antibody after specific antigenic stimulation. In this family, the 5'-nucleotidase deficiency and the pattern of inheritance suggest that the different types of hypogammaglobulinemia may represent a variable expression of a common underlying genetic abnormality.

Adolescent↗
PubMed1980

[Hypnosis and modified hypnotherapeutic methods. Indications and results in hospitalized and ambulatory patients].

164 patients were treated hypnotherapeutically. The therapeutical methods used were heterohypnosis and the so-called gestufte Aktivhypnose (graded active hypnosis), a method which is closely related to autogenous training. In most patients independent continuation of the application of guiding principles in autogenous training was envisaged for stabilizing the results of the hypnotherapy and also achieved. The indications include a wide range of psychovegetative syndromes, including addictions. Especially syndromes showing predominantly vegetative symptoms and a relatively insignificant neurotic component responded most positively to this type of treatment. The results were less satisfactory in patients suffering from pronounced personality disorders. Hynotherapy now supplements psychotherapeutical treatment, hitherto mainly orientated to behaviour therapy, in such a way, that psychotherapy in a general hospital can be realized more effectively.

Autogenic Training↗
PubMed1976

A comparison of process notes and tape recordings. Implications for therapy research.

The basic contention of many researchers is that process notes are not suitable for objective study of psychotherapy. We focus here on our contrasting assumption that process notes may be effectively used for certain kinds of psychotherapy research, particularly that which deals with thematic shifts occurring over a period of time. To test this, three classes of taped memories were examined for thematic shifts: memories of the patient's father, mother, and repetitive memories. The taped memories were then compared with the memories recorded in the analyst's notes. Compared to the tapes, process note memories were fewer in number, significantly condensed, and introduced a variety of distortions into the data. In spite of these differences, judgments by independent raters indicated that in all three classes of memories, the analyst's notes reliably picked up pertinent thematic shifts.

Adult↗