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Biomedical subjects

K Cross

Publications and source records attributed to K Cross.

8 recordsLinked to original sources
PubMed2001

Influenza fusion peptides.

The 'fusion peptides' of a group of enveloped viruses that includes influenza, paramyxo-, retro-and filo-viruses are N-terminal regions of their membrane fusion proteins generated by cleavage of non-functional precursors. For the influenza membrane fusion protein, haemagglutinin (HA), the three-dimensional structures of precursor HA, cleaved HA and fusion-activated HA show that the fusion peptides are located in different positions in all three forms and adopt different structures. Analyses of mutant HAs with changes in fusion peptide sequence indicate the importance of specific residues for membrane-fusion activity and suggest a structure for the fusion peptide in a fusion-active molecule.

Amino Acid Sequence↗
PubMed1995

Solution structure of the B-chain of insulin as determined by 1H NMR spectroscopy. Comparison with the crystal structure of the insulin hexamer and with the solution structure of the insulin monomer.

The solution structure of the isolated B-chain of bovine insulin has been determined by 1H NMR spectroscopy combined with simulated annealing calculations. Complete sequence-specific assignments for the proton resonances are reported together with a set of 309 NOEs used in the structure calculations. Chemical-shift variations from random coil values provide support for the existence of helical regions in the polypeptide chain, as do a characteristic series of d alpha beta(i, i + 3) NOEs from residues B8 to B17. While there is some evidence for a limited degree of conformational averaging over the helical region, in general the helix is relatively well defined and corresponds closely to the helical region seen in the X-ray crystal structure of the insulin hexamer. Other similarities with the crystal structure include turn-like conformations at the carboxy terminal end of the helix and extended strands at both the amino and carboxy termini of the peptide. These similarities between the crystal structure and the isolated B-chain suggest that this peptide has intrinsic folding properties, which allow it to adopt its characteristic structure in intact insulin without the need for extensive cooperative interactions with the A-chain. Despite these general similarities, an important difference between the isolated B-chain and the intact protein occurs in the carboxy terminal region. This region appears significantly more mobile in the isolated B-chain. As a conformational change involving the carboxy terminus has been implicated in receptor binding, the current study of the isolated B-chain provides valuable information on the extent of this region's intrinsic mobility.

Amino Acid Sequence↗
PubMed1993

1H-n.m.r. study of the solution properties and secondary structure of neurotoxin III from the sea anemone Anemonia sulcata.

The solution properties, secondary structure and global fold of the 27-residue polypeptide neurotoxin III (ATX III), from the sea anemone Anemonia sulcata, have been investigated using high-resolution 1H-n.m.r. spectroscopy. Studies of the concentration dependence of the n.m.r. spectrum indicate that the molecule self-associates in the millimolar concentration range useable for n.m.r. analysis, the association being less pronounced at acidic pH values. The dependence on pH of association implies that electrostatic interactions play a role in this process, while the significant concentration-dependent shifts of the aromatic resonances of Tyr-7 and Trp-13 indicate that hydrophobic interactions also contribute. Individual pKa values have been determined for most ionizable groups in the molecule. Sequence-specific resonance assignments were obtained for all protons using a range of two-dimensional homonuclear-correlated and nuclear-Overhauser-effect (nOe) spectra. The secondary structure of the polypeptide was identified from sequential (i, i+1) and medium-range (i, i+2/3/4) nOe connectivities, NH to C alpha H coupling constants, C alpha H chemical shifts, and the location of slowly exchanging backbone-amide protons. ATX III contains no regular alpha-helix or beta-sheet, consisting instead of a network of reverse turns. nOe connectivities between half-cystine residues are consistent with the disulphide pairings 3-17, 4-11 and 6-22. ATX III has a well-defined structure and appears to lack the disordered loop which, in the longer sea anemone toxins (46-49 residues), may be part of the receptor-binding surface.

Amino Acid Sequence↗
PubMed1991

The measurement of referrals for practice audit.

The Royal College of General Practitioners and the Office of Population Censuses and Surveys have collaborated in three national studies of morbidity in general practice at approximately ten-year intervals. This paper presents data derived from the second survey conducted in 1970/71. A comparison of practice referral rates based on different measures is reported, and consideration given to the consequences of the choice of measure on how practices may be perceived. The findings of this study emphasise the need for caution in the interpretation of practice referral data while providing encouragement for general practitioners to engage in open peer review of their practice activities.

Abstracting and Indexing↗
PubMed1991

An examination of practice referral rates in relation to practice structure, patient demography and case mix.

This paper examines the variation in practice referral rates from 53 practices over a twelve-month period. Data from the Second National Morbidity Study were used in relation to practice structure; age, sex and Social Class composition of the patient population; and the case mix by practice. The results show that the age of the patient is an important determinant of the probability of referral, whereas Social Class has little influence. Analysis of the practice-based data showed that practices were highly concordant in their referral activity across sex and age (greater or less than 45 years), sex and Social Class (manual or non-manual), and across chapters of the disease classification. This degree of concordance points to characteristics of the practices rather than patients, and their problems as the main source of variation in practice referral behaviour.

Chi-Square Distribution↗
PubMed1988

Accidental hydrocarbon ingestion cases telephoned to a regional poison center.

One hundred eighty-four telephone calls to the Texas State Poison Center concerning accidental hydrocarbon ingestion were reviewed in an attempt to define the risk of developing any subsequent medical problem requiring therapeutic intervention. Special attention was given to changing symptom severity in an attempt to evaluate its usefulness in predicting future complications. One hundred twenty patients (65%) had no initial symptoms and remained asymptomatic throughout an 18-hour follow-up period. Sixty-two (34%) of patients had symptoms initially but quickly became asymptomatic. Two (1%) developed significant complications (one chemical pneumonitis, one death). These data suggest that the risk of significant complications after accidental hydrocarbon ingestion is low (approximately 1% of patients at risk). Patients who are asymptomatic or who quickly become asymptomatic can be watched safely at home, and referral of asymptomatic patients to a hospital may be unwarranted.

Adolescent↗
PubMed1980

Influence of environmental chemicals on drug therapy in humans: studies with contraceptive steroids.

The effects have been studied of various environmental factors on the variability in response to oral contraceptive steroid therapy in women. Ten- to thirty-fold variations in plasma concentrations of norethisterone, L-norgestrel and ethinyloestradiol have been shown in samples taken 12 h after administration of oral contraceptives in mid-menstrual cycle. Factors shown to be responsible for this variation include passage into the enterohepatic circulation, a variable first-pass effect, and changes in metabolism in the gut wall or liver due to diet, disease, smoking or administration of drugs. Phenobarbitone and the antibiotic rifampicin increase both oestrogen and progestogen metabolism in women and in experimental animals by increasing hepatic and gut wall metabolism. In animals, other antibiotics (ampicillin, neomycin and lincomycin) suppress the gut flora that normally hydrolyse steroid conjugates excreted in bile; enterohepatic circulation or oral contraceptive steroids is thus reduced and their plasma concentrations lowered by up to 90%. In the human, ampicillin has a variable but less dramatic effect on elimination of oral contraceptives. Samples of gut wall mucosa obtained from patients with coeliac disease are defective in their ability to metabolize oral contraceptives. Cigarette smokers eliminate ethinyloestradiol more rapidly than non-smokers; an increased production of reactive steroid metabolites may thus be a cause of vascular disease in women who smoke and take contraceptive steroids.

Animals↗