Engineering multiple properties of a protein by combinatorial mutagenesis

A method for simultaneously engineering multiple properties of a protein, based on the observed additivity of effects of individual mutations, is presented. We show that, for the gene V protein of bacteriophage f1, effects of double mutations on both protein stability and DNA binding affinity are approximately equal to the sums of the effects of the constituent single mutations. This additivity of effects implies that it is possible to deliberately construct mutant proteins optimized for multiple properties by combination of appropriate single mutations chosen from a characterized library.     

Anogenital papillomavirus infection and neoplasia in immunodeficient women

This article reviews the impact of infection with human immunodeficiency virus (HIV) on HPV infections and HPV-associated lesions of the female anogenital tract. Studies investigating HPV infections in HIV-seropositive women are presented as well as the possibility that HIV can influence HPV expression directly through molecular interactions between viral genes and indirectly through immunosuppression. Studies linking HIV infection to invasive cervical cancer and cervical intraepithelial neoplasia are reviewed; recommended protocols for cervical cancer screening in HIV-seropositive women for cervical disease also are presented.     

Menarcheal age in University of Warwick young women

The influence of ischemia on purine nucleotide and their catabolite concentration in human myocardium was investigated during surgery of acquired and congenital heart defects. This was compared with the influence of ischemia on rat heart. Concentrations of adenine and guanine nucleotides and their catabolites were measured in the extracts of heart biopsies taken at the onset of ischemia and at the time of reperfusion. The content of myocardial ATP in human heart decreased from the initial value of 22.3 +/- 1.1 to 14.6 +/- 1.5 nmol/mg protein and total adenine nucleotide pool decreased from 34.2 +/- 1.8 to 27.6 +/- 1.5 nmol/mg protein during the operation. Significant increases in myocardial concentrations of purine catabolites were also observed with the most prominent rise in inosine from below 0.5 at the onset of the ischemia to 3.0 +/- 0.5 nmol/mg protein at the time of reperfusion. A positive correlation was demonstrated between the concentration of purine catabolites in the heart at the end of ischemia with the decrease of both ATP and the total nucleotide pool. An interesting metabolic specificity of the ischemic human heart appeared to be only a small accumulation of inosine monophosphate (IMP). The increase of IMP in the rat heart after ischemia was several-fold higher. Thus, cardiac surgery of congenital and acquired heart defects was associated with a significant decrease in myocardial adenylate pool and a single biopsy collected at the end of ischemia seems to be sufficient to evaluate the extent of this metabolic and possibly functional impairment of the heart.     

Modulation of postural tremors at the wrist by supramaximal electrical median nerve shocks in essential tremor, Parkinson's disease and normal subjects mimicking tremor

The response of postural wrist tremors to supramaximal median nerve stimulation was examined in patients with hereditary essential tremor (n = 10) and Parkinson's disease (n = 9), and in normal subjects mimicking wrist tremor (n = 8). The average frequency of on-going tremor was the same in all three groups. Supramaximal peripheral nerve shocks inhibited and then synchronised the rhythmic electromyographic (EMG) activity of all types of tremor. The duration of inhibition ranged from 90 to 210ms, varying inversely with the frequency of on-going tremor. There was no significant difference in mean duration of inhibition or in the timing of the first peak after stimulation on the average rectified EMG records between the three groups. The degree to which supramaximal peripheral nerve shocks could modulate the timing of rhythmic EMG bursts in the forearm flexor muscles was also quantified by deriving a resetting index. No significant difference in mean resetting index of the three groups was found. These results suggest that such studies cannot be used to differentiate between the common causes of postural wrist tremors.     

Allelotype analysis of uterine leiomyoma: localization of a potential tumor suppressor gene to a 4-cM region of chromosome 7q

The degree and nature of patient involvement in consultations with health professionals influences problem and needs recognition and management, and public accountability. This paper suggests a framework for understanding the scope for patient involvement in such consultations. Patients are defined as co-producers of formal health services, whose potential for involvement in consultations depends on their personal rights, responsibilities and preferences. Patients' rights in consultations are poorly defined and, in the National Health Service (NHS), not legally enforceable. The responsibilities of patients are also undefined. I suggest that these are not to deny, of their own volition, the rights of others, which in consultations necessitate mutuality of involvement through information-exchange and shared decision-making. Preferences should be met insofar as they do not militate against responsibilities and rights.     

Z/I and A-band lattice spacings in frog skeletal muscle: effects of contraction and osmolarity

A-band and Z-line/I-band lattice spacings were measured by small-angle X-ray diffraction from relaxed and isometrically-contracting whole frog sartorius muscles with lattice spacings reduced or swollen by changing the osmolarity of the bathing solution. A-band spacing increased by approximately 3% upon isometric contraction at reduced lattice spacings (245-356 mOsm) and decreased by approximately 1% at swollen spacings (172 mOsm), similarly to the behaviour of skinned muscles upon changing from the relaxed state to rigor. The Z/I lattice underwent a significant lattice expansion (3-8%) upon isometric contraction at all osmolarities, in qualitative agreement (but quantitative disagreement) with results from electron microscopy on mammalian skeletal muscle. Lattice areas calculated for the Z/I and A-band lattices indicate a barrel-shaped sarcomere in the resting state, which may provide a partial explanation for how longitudinal forces produced in the A-band can produce a radial expansive force in the Z-line during contraction. The radial component of cross-bridge stiffness was calculated from the A-band data for contracting muscle, using a lattice stability model incorporating structural, osmotic and electrostatic forces. The calculations gave a radial cross-bridge stiffness during contraction of about 9 x 10(5) N m-2, and outward radial force per thick filament in normal Ringer's solution of 6 x 10(-9) N, corresponding to a radial force per cross-bridge of 10(-11) N.