Biomedical subjects

M Jeeves

Publications and source records attributed to M Jeeves.

7 recordsLinked to original sources

PubMed2001

The stability of compromised interhemispheric processing in callosal dysgenesis and partial commissurotomy.

The persistence and stability of selective deficits in interhemispheric processing resulting from known callosal pathology have been monitored over periods ranging from ten to thirty five years. The present study included five patients: two with complete agenesis of the corpus callosum, one with partial dysgenesis, and two with a partial section of the corpus callosum. A crossed-uncrossed difference task and four bilateral visual matching tasks were administered to these patients and to groups of normal individuals matched on age and intelligence. As expected, all of the patients showed deficits in speed or accuracy relative to the performance of their control groups. The profile of performance for each patient across the five tasks demonstrated a systematic (but not perfectly consistent) relationship with the location and extent of callosal pathology.

Adolescent↗

PubMed2000

Solution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from Rhodospirillum rubrum.

Transhydrogenase is a proton pump found in the membranes of bacteria and animal mitochondria. The solution structure of the expressed, 21.5 kDa, NADP(H)-binding component (dIII) of transhydrogenase from Rhodospirillum rubrum has been solved by NMR methods. This is the first description of the structure of dIII from a bacterial source. The protein adopts a Rossmann fold: an open, twisted, parallel beta-sheet, flanked by helices. However, the binding of NADP(+) to dIII is profoundly different to that seen in other Rossmann structures, in that its orientation is reversed: the adenosine moiety interacts with the first betaalphabetaalphabeta motif, and the nicotinamide with the second. Features in the structure that might be responsible for changes in nucleotide-binding affinity during catalysis, and for interaction with other components of the enzyme, are identified. The results are compared with the recently determined, high-resolution crystal structures of human and bovine dIII which also show the reversed nucleotide orientation.

Amino Acid Sequence↗

PubMed1999

Structural changes in the recombinant, NADP(H)-binding component of proton translocating transhydrogenase revealed by NMR spectroscopy.

We have analysed 1H, 15N-HSQC spectra of the recombinant, NADP(H)-binding component of transhydrogenase in the context of the emerging three dimensional structure of the protein. Chemical shift perturbations of amino acid residues following replacement of NADP+ with NADPH were observed in both the adenosine and nicotinamide parts of the dinucleotide binding site and in a region which straddles the protein. These observations reflect the structural changes resulting from hydride transfer. The interactions between the recombinant, NADP(H)-binding component and its partner, NAD(H)-binding protein, are complicated. Helix B of the recombinant, NADP(H)-binding component may play an important role in the binding process.

Amino Acid Sequence↗

PubMed1999

Sulcus fixation without capsular support in children.

PURPOSE: To evaluate long-term follow-up in eyes of children who had sulcus fixation of an intraocular lens (IOL) without capsular support. SETTING: St. Eriks Eye Hospital/Karolinska Institute, Stockholm, Sweden. METHODS: This retrospective study included 21 eyes of 13 children. Seven eyes had Marfan's syndrome, 7 essential lens dislocation, 2 perforation with lens injury, and 5 spherophakia. The IOL implantation was primary in 16 eyes and secondary in 5 eyes. Lensectomy was performed with a limbal approach. An IOL with holes in the haptics was sutured in the sulcus, with the knots buried in the scleral bed. RESULTS: Mean patient age was 5.8 years +/- 2.6 (SD). Follow-up ranged from 9 to 33 months. No complications occurred during surgery. In all cases after IOL implantation, best corrected visual acuity was equal to or better than preoperatively. After surgery, no opacification of the visual axis, secondary glaucoma, or retinal complication was recorded. Posterior synechia formation occurred in 4 eyes, and 4 had cells on the IOL surface in 2 eyes, the IOL optic subluxated into the anterior chamber with the haptics in place. Both cases were successfully treated with pilocarpine 4%. CONCLUSION: Our results suggest that sulcus fixation of an IOL without capsular support is an option to correct aphakia in children.

Aphakia, Postcataract↗

PubMed1999

Studies of the Escherichia coli Trp repressor binding to its five operators and to variant operator sequences.

The Escherichia coli Trp repressor binds to promoters of very different sequence and intrinsic activity. Its mode of binding to trp operator DNA has been studied extensively yet remains highly controversial. In order to examine the selectivity of the protein for DNA, we have used electromobility shift assays (EMSAs) to study its binding to synthetic DNA containing the core sequences of each of its five operators and of operator variants. Our results for DNA containing sequences of two of the operators, trpEDCBA and aroH are similar to those of previous studies. Up to three bands of lower mobility than the free DNA are obtained which are assigned to complexes of stoichiometry 1 : 1, 2 : 1 and 3 : 1 Trp repressor dimer to DNA. The mtr and aroL operators have not been studied previously in vitro. For DNA containing these sequences, we observe predominantly one retarded band in EMSA with mobility corresponding to 2 : 1 complexes. We have also obtained retardation of DNA containing the trpR operator sequence, which has only been previously obtained with super-repressor Trp mutants. This gives bands with mobilities corresponding to 1 : 1 and 2 : 1 complexes. In contrast, DNA containing containing a symmetrized trpR operator sequence, trpRs, gives a single retarded band with mobility corresponding solely to a 1 : 1 protein dimer-DNA complex. Using trpR operator variants, we show that a change in a single base pair in the core 20 base pairs can alter the number of retarded DNA bands in EMSA and the length of the DNase I footprint observed. This shows that the binding of the second dimer is sequence selective. We propose that the broad selectivity of Trp repressor coupled to tandem 2 : 1 binding, which we have observed with all five operator sequences, enables the Trp repressor to bind to a limited number of sites with diverse sequences. This allows it to co-ordinately control promoters of different intrinsic strength. This mechanism may be of importance in a number of promoters that bind multiple effector molecules.

Bacterial Proteins↗

PubMed1996

NMR studies of the Escherichia coli Trp repressor.trpRs operator complex.

To understand the specificity of the Escherichia coli Trp repressor for its operators, we have begun to study complexes of the protein with alternative DNA sequences, using 1H-NMR spectroscopy. We report here the 1H-NMR chemical shifts of a 20-bp oligodeoxynucleotide containing the sequence of a symmetrised form of the trpR operator in the presence and absence of the holorepressor. Deuterated protein was used to assign the spectrum of the oligodeoxynucleotide in a 37-kDa complex with the Trp holorepressor. Many of the resonances of the DNA shift on binding to the protein, which suggests changes in conformation throughout the sequence. The largest changes in shifts for the aromatic protons in the major groove are for A15 and G16, which are thought to hydrogen bond to the protein, possibly via water molecules. We have also examined the effect of DNA binding on the corepressor, tryptophan, in this complex. The indole proton resonance of the tryptophan undergoes a downfield shift of 1.2 ppm upon binding of DNA. This large shift is consistent with hydrogen bonding of the tryptophan to the phosphate backbone of the trpR operator DNA, as in the crystal structure of the holoprotein with the trp operator.

Bacterial Proteins↗

PubMed1980

Comparison of the effects of transcortical and transcallosal removal of intraventricular tumours.

Intelligence and memory functions were tested in 2 patients in whom the corpus callosum had been partially sectioned to remove intraventricular cysts or tumours and in 2 patients in whom similarly-located cysts or tumours had been removed transcortically. A patient with congenital absence of the corpus callosum was also tested. Callosal lesions per se did not appear to be responsible for memory deficits.

Adult↗