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Biomedical subjects

D Williamson

Publications and source records attributed to D Williamson.

At least 19 recordsLinked to original sources
PubMed1992

Structure-function relationships in the low-affinity mutant haemoglobin Aalborg (Gly74 (E18)beta----Arg).

Haemoglobin Aalborg (Gly74 (E18)beta----Arg) has a reduced oxygen affinity, in both the absence and the presence of organic phosphates; it has a raised affinity for organic phosphates, and it is moderately unstable. By contrast, haemoglobin Shepherds Bush (Gly74 (E18)beta----Asp) has an increased oxygen affinity in both the absence and the presence of organic phosphates, a diminished affinity for organic phosphates and is also unstable. We have determined the crystal structure of deoxyhaemoglobin Aalborg at 2.8 A resolution and compared it to the structures of deoxy- and oxyhaemoglobin A and of deoxyhaemoglobin Shepherds Bush. The guanidinium group of Arg74(E18)beta protrudes from the haem pocket and donates hydrogen bonds to the E and F helices. The carboxylate group of Asp74(E18)beta forms a hydrogen bond only with residue EF6 and is partially buried, which may be why haemoglobin Shepherds Bush appears to be more unstable than haemoglobin Aalborg. To discover why the latter has a low oxygen affinity, we superimposed the B, G and H helices of haemoglobin A, whose conformation is known to be unaffected by ligand binding, on those of haemoglobin Aalborg. This also brought helices E and the haems into superposition, but revealed a shift of the F helix of deoxyhaemoglobin Aalborg towards the EF-corner. This shift is opposite to that which occurs on ligand binding and on transition to the quaternary oxy-structure, and is linked to an increased tilt of the proximal histidine residue away from the haem axis. Since the relative positions of helices E and F and of the haem group are thought to be the main determinants of the changes in oxygen affinity, the shift of helix F may account for the reduced oxygen affinity of haemoglobin Aalborg. The shift may be due to a combination of steric and electrostatic effects introduced by the arginine residue's side-chain. The effects of the arginine and aspartate substitutions at position E18 beta on the 2,3-diphosphoglycerate affinity are equal and opposite. They can be quantitatively accounted for by the electrostatic attraction or repulsion by the oppositely charged side-chains.

Amino Acid Sequence↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1990

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↗
PubMed1978

The diagnosis of microscopic carcinoma of the esophagus.

Microscopic squamous cell carcinoma of the esophagus with early submucosal spread was diagnosed in two patients with hiatal hernia and evidence of esophageal reflux. The lesions were not suggestive of malignancy on endoscopic examination. Both patients are known to be alive more than one year after resection and presumably without recurrence. More liberal use of endoscopic brush cytology and biopsy or intubation cytology particularly in the cases at high risk, might substantially improve the chances of very early diagnosis and favorably alter the present grim mortality rate.

Biopsy↗
PubMed1977

Enhancement of urethan tumorigenesis in mouse lung by butylated hydroxytoluene.

Intraperitoneal injection of the antioxidant butylated hydroxytoluene (BHT) produces cell proliferation in mouse lungs within 2-4 days. We examined whether the presence of an increased number of proliferating lung cells would influence urethan tumorigenesis. Male Swiss-Webster mice were treated with 1 mg urethan/g before, during, or after BHT-stimulated cell growth in the lung. The number of pulmonary tumors found 13-15 weeks later was not different in BHT-treated mice compared to that in controls. On the other hand, repeated stimulation of cell growth after urethan treatment enhanced tumorigenesis. Male Swiss-Webster and A/J mice were given a single dose of urethan (1 mg/g) and, beginning 7 days later, weekly injections of BHT or corn oil. Repeated injections of BHT significantly increased the yield of lung tumors in both strains. Weekly injections of BHT into mice pretreated with 0.9% NaCl reduced the number of spontaneous pulmonary adenomas.

Animals↗
PubMed1977

Praecordial ST segment elevation. New technique for continuous recording and analysis.

The measurement of praecordial ST segment elevation after myocardial infarction is of value in assessing the natural history of ischaemic injury and the effectiveness of intervention. Hand analysis is, however, time consuming and inaccurate. A technique for continuous recording from 35 praecordial leads and subsequent computer analysis is presented, together with illustrative case studies. Changes in body posture and in heart rate are of importance in subsequent data interpretation.

Adult↗
PubMed1976

Biochemical paramters of BHT-induced cell growth in mouse lung.

Male mice of 7 different strains were injected i.p. with 400 mg/kg of butylated hydroxytoluene (BHT). 2 and 4 days later, the incorporation of thymidine into pulmonary DNA was significantly increased in all treated animals and this was accompanied by an increase in lung weight and pulmonary DNA. Thymidine kinase activity and DNA polymerase activity were enhanced in the lungs of BHT-treated animals and maximum activity of these enzymes appeared to precede maximum thymidine incorporation by 24 h. 3 days after BHT a good correlation was found between administered dose and thymidine kinase activity. Measuring the activity of this enzyme might serve as a convenient biochemical marker to follow and to quantitate BHT-produced cell proliferation in lung. The concentrations of cyclic AMP and the activity of adenylate cyclase were not altered by BHT on days 1-9 after administration. BHT produced also some dose-dependent, time-dependent increases in the activities of pulmonary 5'-nucleotidase and glucose-6-phosphate dehydrogenase (G6PDH), but had little effect on isocitric dehydrogenase (ICDH), pyruvate kinase (PK) and lactic dehydrogenase (LDH).

Animals↗