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Biomedical subjects

M Sutcliffe

Publications and source records attributed to M Sutcliffe.

16 recordsLinked to original sources

Twin-twin transfusion syndrome in a dizygotic monochorionic-diamniotic twin pregnancy.

We present a case of twin-twin transfusion syndrome with discordant gender. Monochorionicity was confirmed by surgical pathology. Cytogenetic analysis showed normal 46,XX and 46,XY karyotypes. Microsatellite analysis using reliable pericentromeric markers was consistent with dispermic fertilization of two separate ova. This suggests that monochorionicity, rather than zygosity, may be responsible for the development of placental vascular anastomoses.

Abortion, Spontaneous↗

Survey of methods of teaching and learning in undergraduate pharmacology within UK higher education.

Many of the pharmacology teachers surveyed in a questionnaire on pharmacology teaching and learning are aware of nontraditional teaching and learning methods and believe they are both appropriate to the discipline and effective in producing learning gain in the students. The reasons that nontraditional teaching methods are not used extensively include a shortage of staff time together with a perception that nontraditional teaching methods are staff-time intensive, a lack of effective motivation and reward of staff by their institutions for implementing nontraditional teaching methods and a shortage of the appropriate facilities and resources required. The questionnaire and its results are discussed in this article.

Adult↗

Steady-state and picosecond-time-resolved fluorescence studies on the recombinant heme domain of Bacillus megaterium cytochrome P-450.

The conformational changes associated with the interaction of sodium laurate with the recombinant heme domain for cytochrome P-450BM3 have been investigated by steady-state and picosecond-time-resolved fluorescence spectroscopy. The steady-state quenching experiments show that while all the five tryptophan residues are accessible to acrylamide in the free enzyme as well as the enzyme x substrate complex, the number of tryptophan residues accessible to ionic quenchers decreases on interaction of the substrate with the enzyme. This indicates that some of the tryptophan residues move towards the core of the protein on interaction with the substrate. The number of tryptophan residues accessible to the solvent as determined by the calculation of the solvent-accessible area for the free enzyme agrees with the values obtained by the quenching experiments. The time-resolved fluorescence studies carried out by means of the time-correlated single-photon-counting technique show that the fluorescence-decay curve is best fitted to a three-exponential model (0.2, 1.0 and 5.4 ns). Lifetime distributions, as recovered by the maximum-entropy method, agree with the discrete exponential model. The binding of the substrate does not lead to any significant change in the lifetime components of the enzyme, indicating that the tryptophan residues are possibly away from the substrate-binding domain. The decay-associated emission spectra and the magnitudes of amplitude of different lifetimes indicate that the shortest lifetime component (tau1) originates from the three tryptophan residues that are completely or partially accessible to the solvent, and tau2 originates from the tryptophan residues that are buried in the core of the enzyme and not accessible to the solvent. X-ray crystallographic data and solvent-acessible-area calculations have been used to identify these residues.

Bacillus megaterium↗

Uniparental isodisomy of chromosome 14 in two cases: an abnormal child and a normal adult.

Uniparental disomy (UPD) of a number of different chromosomes has been found in associated with abnormal phenotypes. A growing body of evidence for an imprinting effect involving chromosome 14 has been accumulating. We report on a case of paternal UPD of chromosome 14 studied in late gestation due to polyhydramnios and a ventral wall hernia. A prenatal karyotype documented a balanced Robertsonian 14:14 translocation. The baby was born prematurely with hairy forehead, retrognathia, mild puckering of the lips and finger contractures. Hypotonia has persisted since birth and at age one year, a tracheostomy for laryngomalacia and gastrostomy for feeding remain necessary. Absence of maternal VNTR polymorphisms and homozygosity of paternal polymorphisms using chromosome 14 specific probes at D14S22 and D14S13 loci indicated paternal uniparental isodisomy (pUPID). Parental chromosomes were normal. We also report on a case of maternal UPD in a normal patient with a balanced Robertsonian 14:14 translocation and a history of multiple miscarriages. Five previous reports of chromosome 14 UPD suggest that an adverse developmental effect may be more severe whenever the UPD is paternal in origin. This is the second reported patient with paternal UPD and the fifth reported with maternal UPD, and only few phenotypic similarities are apparent. Examination of these chromosome 14 UPD cases of maternal and paternal origin suggests that there are syndromic imprinting effects.

Abnormalities, Multiple↗

Selective reovirus infection of murine hepatocarcinoma cells during cell division. A model of viral liver infection.

Reovirus type 1, strain Lang (1/L), can infect hepatocytes in vivo only after hepatocellular damage is induced by hepatotoxins, surgical trauma, resection, or profound immunosuppression. To examine the role of cell cycle and cellular differentiation on liver cell susceptibility to reovirus infection, a murine hepatocarcinoma cell line, Hepa 1/A1, was infected with reovirus and assayed for the presence of infectious virus or reovirus antigen in cells. Despite a > 95% binding of reovirus to hepatocarcinoma cells as indicated by cytometric analysis; only 10% of hepatoma cells contained infectious virus by infectious center assay. In comparison, 100% of L cells were infected. Analysis of intracellular reovirus antigen revealed its presence in dividing but not in quiescent hepatocytes. This correlation of cellular division and cell capacity to support viral replication suggests that induction of hepatocyte proliferation may be a mechanism for liver susceptibility to reovirus infection.

Animals↗

18th Sir Hans Krebs lecture. Knowledge-based protein modelling and design.

A systematic technique for protein modelling that is applicable to the design of drugs, peptide vaccines and novel proteins is described. Our approach is knowledge-based, depending on the structures of homologous or analogous proteins and more generally on a relational data base of protein three-dimensional structures. The procedure simultaneously aligns the known tertiary structures, selects fragments from the structurally conserved regions on the basis of sequence homology, aligns these with the 'average structure' or 'framework', builds on the loops selected from homologous proteins or a wider database, substitutes sidechains and energy minimises the resultant model. Applications to modelling an homologous structure, tissue plasminogen activator on the basis of another serine proteinase, and to modelling an analogous protein, HIV viral proteinase on the basis of aspartic proteinases, are described. The converse problem of ab initio design is also addressed: this involves the selection of an amino acid sequence to give a particular tertiary structure, in this case a symmetrical domain of two Greek-key motifs.

Base Sequence↗

Cephalexin levels in human bile in presence of biliary tract disease.

Cephalexin was given to 24 patients before and after operation on the bile ducts and gall bladder. Two patients had obstructive jaundice. Samples of the bile were taken either directly from the gall bladder at operation or via the T-tube. Cephalexin was excreted in the bile, peak levels being obtained after two to three hours. These levels could be raised if probenecid was given concurrently. Higher levels were found in patients with functioning gall-bladders. A trial of cephalexin seems justified for the treatment of typhoid carriers.

Bile↗