Polycythaemia and microcytosis arising from the combination of a new high oxygen affinity haemoglobin (Hb luton, alpha 89 His-->Leu) and alpha thalassaemia trait.
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Adult↗
Biomedical subjects
D Williamson
Publications and source records attributed to D Williamson.
A family with haemolytic anaemia and three beta-globins: the deletion in haemoglobin Atlanta-Coventry (beta 75 Leu----Pro, 141 Leu deleted) is not present at the nucleotide level.
Analyses of haemoglobin from a family with an unstable haemoglobin haemolytic anaemia demonstrated that the affected individuals had three beta-globins, namely, normal (beta A), Atlanta (beta At) with a mutation of beta 75 Leu----Pro, and beta-Atlanta-Coventry (beta At-Co) with mutation of beta 75 Leu----Pro and beta 141 Leu deleted. These were present in the ratio 66:23:11 respectively. The structure of the beta-globin cluster, however, was found to be normal by Southern blotting; also cytogenetic analysis failed to show any abnormality. DNA sequence analyses demonstrated the presence of the beta At mutation in genomic DNA isolated from leucocytes but the Coventry deletion of 141 Leu in beta At-Co was not present in genomic DNA. PCR amplification of the beta-globin cDNA and direct sequencing of the product also failed to demonstrate the Coventry deletion. Thus, it appears that the absence of 141 Leu in the beta At-Co globin is a consequence of the beta At mutation in these patients and that both beta At and beta At-Co are the product of a single gene. This unusual conclusion is paralleled in the bizarre case of Hb Vicksburg where the deletion of a leucine at beta 75 is not coded for in genomic DNA.
Anemia, Hemolytic↗
A new alpha chain variant, Hb Turriff [alpha 99(G6)Lys----Glu]: the interference of abnormal hemoglobins in Hb A1c determination.
Hb Turriff is a new hemoglobin variant which we have identified in a diabetic individual. During the determination of Hb A1c by high performance liquid chromatography, an inappropriately elevated result was found to be due to the abnormal hemoglobin chromatographing with the Hb A1c fraction. This new hemoglobin variant, Hb Turriff [alpha 99(G6)Lys----Glu], is not associated with any hematological disturbance, and family investigations indicate that it has arisen as a de novo mutation.
Adult↗
Awareness and practice of HIV and hepatitis B guidelines in a psychiatric hospital.
Guidelines for safe practice are considered to be an important measure in preventing HIV and Hepatitis B infection in health care staff. Awareness and practice of health board guidelines in a psychiatric hospital were assessed by means of a questionnaire. The results suggest that such guidelines may not be read by certain staff groups, especially junior medical staff. In addition, there was no difference in practice between staff who had read the guidelines and those who had not. There may be a need for more active encouragement of safe practice in order to prevent spread of infection to staff.
HIV Infections↗
The incidence of dysfunctional antithrombin variants: four cases in 210 patients with thromboembolic disease.
210 patients, with a history of venous thrombosis, have undergone prothrombotic investigations. In nine cases a consistent deficiency of antithrombin was identified. In five there was a reduction in the plasma antigenic concentration of antithrombin and in a further four cases deficiency was due to the presence of a dysfunctional antithrombin variant. The variants have all been characterized by DNA analysis and in three the mutations have been confirmed by peptide sequencing (antithrombin Basel (41 Pro to Leu). Hamilton (382 Ala to Thr). Cambridge I (384 Ala to Pro) and Cambridge II (384 Ala to Ser). The incidence of antithrombin deficiency in patients with a history of venous thrombosis has previously been quoted at between 2% and 3%: there is no published data available on the incidence of antithrombin variants. In our series 5% of patients who presented before the age of 40 years had antithrombin deficiency, and 2% of the total number of patients investigated had a dysfunctional variant. Our figures indicate that a significant number of cases of antithrombin deficiency are due to dysfunctional variants and that the true incidence of antithrombin deficiency in patients with a history of venous thrombosis is in the order of 5%.
Adult↗
Anabolic steroid use outside competition.
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Anabolic Agents↗
Two-dimensional nMR study of bleomycin and its zinc(II) complex: reassignment of 13C resonances.
Two-dimensional NMR experiments--one bond 1H-13C correlation spectroscopy and heteronuclear multiple bond correlation spectroscopy, both performed in the reverse detection mode--have been employed to unambiguously assign all of the 13C resonances of the antibiotic bleomycin and its zinc(II) complex. Previous 1H resonance assignments of bleomycin (Chen et al. (1977) Biochemistry 16, 2731-2738) were confirmed on the basis of homonuclear Hartmann-Hahn and homonuclear COSY experiments. The 13C assignments differ substantially from those previously obtained by other investigators (Naganawa et al., (1977) J. Antibiot. 30, 388-396; Dabrowiak et al., (1978) Biochemistry 17, 4090-4096) but are in agreement with those reported by Akkerman et al. (1988) (Magn. Reson. Chem. 26, 793-802). The more recent study employed similar two-dimensional correlation experiments (performed in the direct detection mode) in conjunction with attached proton tests. Their study often required model compound data to identify carbonyls adjacent to aliphatic moieties. Previous 13C NMR studies of the structure, pH titration, and molecular dynamics of bleomycin and its zinc complex have been reinterpreted in terms of the revised assignments.
Bleomycin↗
Characterization of Hb Aalborg, a new unstable hemoglobin variant, by fast atom bombardment mass spectrometry.
Hb Aalborg is a new unstable hemoglobin variant found in association with mild anemia. Heinz bodies were readily inducible in red cells but there was no specific evidence of hemolysis and the variant therefore appears to be without significant clinical effect. The amino acid replacement was identified by fast atom bombardment mass spectrometry and is that of Gly----Arg at position beta 74 (E18). Hb Aalborg is moderately unstable.
Anemia↗
Alpha thalassaemia in the Maori: a family study.
Twelve members of a Maori family were investigated for alpha-thalassaemia after a provisional diagnosis of thalassaemia had been made on the basis of chronic hypochromic microcytic red cell indices. Ten family members were shown to have the 3.7 kb deletion form of alpha-thalassaemia; two of these were homozygous for this deletion (-alpha/-alpha); eight had the single deletion (-alpha/alpha alpha). While anaemia was not a significant finding, the degree of hypochromicity and microcytosis correlated well with the alpha globin gene status of individual family members. This and other studies provide evidence that alpha-thalassaemia is a significant contributor to the chronic mild anaemia of the Maori.
Adolescent↗
A new doubly substituted sickling haemoglobin: HbS-Oman.
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Adult↗
Cortisol secretion in adolescents with major depressive disorder.
Plasma cortisol concentrations were determined every 20 min for 24 h, in a nonstressful environment, among 48 rigorously assessed, mostly outpatient, drug-free adolescent subjects during an episode of major depression (MDD) and among 40 normal adolescent subjects. There were no significant differences in the 24-h mean, peak, or nadir, or the time of the nocturnal rise, in plasma cortisol in the 2 groups. Analyses of different subgroups of MDD adolescents according to suicidality, severity of depression, separation anxiety, psychotic subtype, endogenicity, duration of episode, and sex also revealed no significant group differences. Only one adolescent (with MDD) was identified clearly as a hypersecretor of cortisol. These results indicate that abnormalities of spontaneous cortisol secretion are an unusual finding among adolescents with major depression when studied in a nonstressful environment.
Adolescent↗
Chromatographic and spectral investigations on the in vivo metabolites of 6-nitrobenzo[a]pyrene.
6-Nitrobenzo[a]pyrene (6-NBaP) occurs in the environment, is mutagenic in the Ames assay in the presence of added S9 and is carcinogenic to male but not female mouse liver when injected intraperitoneally (i.p.) into mice. In order to understand what kinds of active metabolites could have been produced in vivo, both male and female mice were injected i.p. with 6-NBaP in dimethyl sulfoxide. Twenty-four hours after injection, urine, feces, blood, liver and spleen (non-target tissue) were examined for metabolites by chromatographic and high-resolution mass spectral means. On the basis of the mass spectral fragmentation patterns of synthetic and metabolic standards, it was observed that both male and female animals excreted ring-hydroxylated metabolites of 6-NBaP in the urine to differing extents. Male animals additionally excreted 6-aminobenzo[a]pyrene and the significance of this observation is discussed.
Aging↗
Forbidden Food Survey: measure of bulimic's anticipated emotional reactions to specific foods.
The Forbidden Food Survey is an instrument that was designed for use with eating disordered individuals. The first experiment in this study includes a description of the Forbidden Food Survey and the reliability and internal consistency of its scales. The second investigation examined the discriminant validity of the Forbidden Food Survey by comparing the responses of three groups: bulimic binge-purgers, bulimic binge-eaters, and normals. The Forbidden Food Survey was found to differentiate the two bulimic groups on two scales, high caloric foods, medium calorie foods, and milk. As predicted from the anxiety model of bulimia, binge-purgers consistently reported stronger negative emotional responses to these foods than did the other groups. In the third experiment, bulimic binge-purgers were compared on Forbidden Food Survey responses to obese and normal subjects. Again, binge purgers were found to respond with stronger negative responses than obese and normals. These studies support the reliability and discriminant validity of the Forbidden Food Survey with eating disordered individuals.
Adolescent↗
A new unstable and low oxygen affinity hemoglobin variant: Hb J-Auckland [beta 25(B7)Gly----Asp].
Hb J-Auckland is a new hemoglobin variant with the amino acid substitution beta 25(B7)Gly----Asp. It is mildly unstable and has a low oxygen affinity. The propositus and a son, both heterozygous for Hb J-Auckland, have marginally low Hb values but no apparent clinical symptoms.
Amino Acid Sequence↗
Ring oxidation of 6-nitrobenzo (a) pyrene by female mouse liver.
6-Nitrobenzo (a) pyrene (6-NBaP) is an environmental contaminant. In bacterial mutagenesis assays, 6-NBaP requires rat liver S9 enzymes for its activity. Chemical characterization of metabolites of 6-NBaP produced by male rat liver microsomes showed them to be ring-hydroxylated (both mono- and dihydroxy) derivatives. Thus, metabolic activation of 6-NBaP may occur via ring oxidation. It has been shown by others that when injected intraperitoneally into newborn mice, 6-NBaP was carcinogenic to male, but not to female, mouse liver. The nitro-hydrocarbon was not carcinogenic to the lungs of either sex. We have examined the metabolism of 6-NBaP by the liver of a non-susceptible female mouse and observed the formation of ring-hydroxylated metabolites of 6-NBaP. In view of this observation, we suggest that ring hydroxylation alone may not be sufficient in explaining the carcinogenicity of 6-NBaP in male and not in female mice.
Acetylation↗
HCMR interview: David Williamson. Interview by Montague Brown.
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Delivery of Health Care↗
Two de novo mutations in one beta globin chain: hemoglobin Atlanta-Coventry, beta 75 Leu----Pro and beta 141 Leu deleted.
Reverse phase HPLC analysis of a hemolysate from a patient with hemolytic anemia revealed the presence of three different beta globins. Reverse phase Peptide mapping and amino acid analysis indicated that one was normal beta A (66%), one was beta Atlanta (beta 75 Leu----Pro, 23%) and the third, beta Atlanta-Coventry, contained two mutations beta 75 Leu----Pro and beta 141 Leu deleted. The parents and four siblings of the propositus had only beta A chains, while two of his children inherited the beta Atlanta and beta Atlanta-Coventry chains from him, and beta A Chains from their mother. His third child was normal, possessing only beta A chains.
Adult↗
Polycythaemia associated with a new haemoglobin variant: haemoglobin Palmerston North beta 23 (B5) val----phe.
A new haemoglobin variant, with increased oxygen affinity, has been identified in a patient with a long history of polycythaemia. This new haemoglobin, Hb Palmerston North, has an amino acid substitution of valine to phenylalanine at position beta 23 (B5). The increased oxygen affinity is accompanied by a decrease in globin stability which was responsible for the laboratory detection of the haemoglobinopathy.
Aged↗