PubMed Health⌕ Search

Biomedical subjects

M Timms

Publications and source records attributed to M Timms.

10 recordsLinked to original sources
PubMed2001

Cytochrome oxidase subunit VI of Trypanosoma brucei is imported without a cleaved presequence and is developmentally regulated at both RNA and protein levels.

Mitochondrial respiration in the African trypanosome undergoes dramatic developmental stage regulation. This requires co-ordinated control of components encoded by both the nuclear genome and the kinetoplast, the unusual mitochondrial genome of these parasites. As a model for understanding the co-ordination of these genomes, we have examined the regulation and mitochondrial import of a nuclear-encoded component of the cytochrome oxidase complex, cytochrome oxidase subunit VI (COXVI). By generating transgenic trypanosomes expressing intact or mutant forms of this protein, we demonstrate that COXVI is not imported using a conventional cleaved presequence and show that sequences at the N-terminus of the protein are necessary for correct mitochondrial sorting. Analyses of endogenous and transgenic COXVI mRNA and protein expression in parasites undergoing developmental stage differentiation demonstrates a temporal order of control involving regulation in the abundance of, first, mRNA and then protein. This represents the first dissection of the regulation and import of a nuclear-encoded protein into the cytochrome oxidase complex in these organisms, which were among the earliest eukaryotes to possess a mitochondrion.

Amino Acid Sequence↗
PubMed2000

Life-cycle differentiation in Trypanosoma brucei: molecules and mutants.

Differentiation between bloodstream and tsetse midgut procyclic forms during the life cycle of the African trypanosome is an attractive model for the analysis of stage-regulated events. In particular, this transformation occurs synchronously, there are well-defined markers for stage-regulated processes and cell lines with specific defects in differentiation have been identified. This combination of tools, combined with the developing Trypanosoma brucei genome database is allowing its underlying controls to be investigated at the molecular and cytological levels. This paper examines some recent discoveries that illuminate some of the key events during trypanosome life-cycle progression.

Animals↗
PubMed1996

Pre-exercise glycerol hydration improves cycling endurance time.

The effects of glycerol ingestion (GEH) on hydration and subsequent cycle ergometer submaximal load exercise were examined in well conditioned subjects. We hypothesized that GEH would reduce physiologic strain and increase endurance. The purpose of Study I (n = 11) was to determine if pre-exercise GEH (1.2 gm/kg glycerol in 26 ml/kg solution) compared to pre-exercise placebo hydration (PH) (26 ml/kg of aspartame flavored water) lowered heart rate (HR), lowered rectal temperature (Tc), and prolonged endurance time (ET) during submaximal load cycle ergometry. The purpose of Study II (n = 7) was to determine if the same pre-exercise regimen followed by carbohydrate oral replacement solution (ORS) during exercise also lowered HR, Tc, and prolonged ET. Both studies were double-blind, randomized, crossover trials, performed at an ambient temperature of 23.5-24.5 degrees C, and humidity of 25-27%. Mean HR was lower by 2.8 +/- 0.4 beats/min (p = 0.05) after GEH in Study I and by 4.4 +/- 1.1 beats/min (p = 0.01) in Study II. Endurance time was prolonged after GEH in Study I (93.8 +/- 14 min vs. 77.4 +/- 9 min, p = 0.049) and in Study II (123.4 +/- 17 min vs. 99.0 +/- 11 min, p = 0.03). Rectal temperature did not differ between hydration regimens in both Study I and Study II. Thus, pre-exercise glycerol-enhanced hyperhydration lowers HR and prolongs ET even when combined with ORS during exercise. The regimens tested in this study could potentially be adapted for endurance activities.

Adult↗
PubMed1994

Preliminary experiences with microscopic tonsillectomy.

Experiences with a modified technique of tonsillectomy are described. The surgery is performed viewing the tonsil through the operating microscope and using the bipolar diathermy forceps for dissection and diathermy of blood vessels. In a pilot-study of 70 patients, the microscopic method was found to be an elegant technique which substantially reduced intra-operative blood loss and did not prolong surgery. Post-operative morbidity will be assessed in a further study.

Adolescent↗
PubMed1994

Hemodynamic effects of nasal and face mask continuous positive airway pressure.

Studies of the hemodynamic effects of nasal continuous positive airway pressure (n-CPAP) in normal subjects have had conflicting results. The largest study (n = 19) found no effect of up to 15 cm H2O on heart rate (HR), cardiac stroke volume (SV), or cardiac index. We hypothesized that n-CPAP, by increasing intrathoracic pressure, should decrease SV and cardiac output (CO) in a dose-dependent fashion in normal subjects. We also hypothesized that mouth position, i.e., open or closed, could affect intrathoracic pressure and thus SV and CO. Six normal subjects were tested with four levels of CPAP (5, 10, 15, and 20 cm H2O) under three mask conditions-face mask and nasal mask with the mouth open (mo) or with the mouth closed (mc). Noninvasive pulsed Doppler measurements of SV and HR were made under each condition. N-CPAP (mc) and face mask CPAP (f-CPAP) resulted in significant dose-dependent decreases of SV-24 +/- 5 ml (21%) and 33 +/- 5 ml (28%), respectively--from baseline to 20 cm H2O (p < 0.05). HR were unchanged and CO significantly decreased with n-CPAP(mc) and with f-CPAP, 1.6 +/- 0.38 L/min (23%) and 2.29 +/- 0.54 L/min (31%), respectively, from baseline to 20 cm H2O (p < 0.05). Esophageal pressure measurements verified increasing intrathoracic pressure with increasing levels of f-CPAP and n-CPAP (mc) but not with n-CPAP (mo). In conclusion, n-CPAP (mc) and f-CPAP resulted in significant and similar dose-dependent decreases in SV and CO.

Adult↗
PubMed1993

An Escherichia coli gene showing a potential ancestral relationship to the genes for the mitochondrial import site proteins ISP42 and MOM38.

An ORF (OrfT) of 1911 base pairs, upstream of the hip operon in Escherichia coli at map position 33.82 has been identified. The protein encoded by this sequence is predicted to have a molecular mass of 68,249 Da and the carboxyterminal 276 residues shows 26.8% and 25.4% identity with the import site proteins ISP42 and MOM38 from the mitochondrial outer membrane of Saccharomyces cerevisiae and Neurospora crassa, respectively. These mitochondrial membrane proteins have been shown to be essential components of the protein translocation apparatus in yeast. These similarities raise the possibility that OrfT might represent the bacterial gene from which these eukaryotic genes evolved.

Amino Acid Sequence↗
PubMed1991

Identification of a GTP-binding protein in the contact sites between inner and outer mitochondrial membranes.

Whilst investigating whether GTP hydrolysis may be required for the import of preproteins into mitochondria we have found that a GTP-binding protein is located at the contact sites between mitochondrial inner and outer membranes. When mitochondrial outer membranes purified from rat liver were UV-irradiated in the presence of [alpha-32P]GTP, a 52 kDa protein was radiolabelled, whereas [alpha-32P]ATP did not label this protein. GTP-binding proteins were also labelled in the cytosolic and microsomal fractions, but the 52 kDa protein was concentrated in mitochondrial membranes and was the only protein specifically labelled by GTP in these membranes. Fractionation of mitochondrial membrane vesicles into outer membranes, inner membranes and contact sites between outer and inner membranes showed that the GTP-binding activity was highly enriched in contact sites, the location at which preprotein import is believed to occur. A protein of almost identical size was also found to be labelled in mitochondria from yeast.

Adenosine Triphosphate↗
PubMed1988

A new cryoprobe with advantages in turbinate freezing.

Freezing of the turbinates has an established role in the relief of nasal obstruction in the conditions of vasomotor and allergic rhinitis. However, present designs are limited in being bulky to use. By application of cryosurgical principles a probe has been designed which is only 2 mm. wide compared with 6 mm. of a standard probe (5N13) and which freezes as well as the standard probe in-vitro and in-vivo.

Adolescent↗