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Biomedical subjects

M Viljoen

Publications and source records attributed to M Viljoen.

At least 19 recordsLinked to original sources
PubMed1999

Transcriptional regulation of the Schizosaccharomyces pombe malic enzyme gene, mae2.

The NAD-dependent malic enzyme from Schizosaccharomyces pombe catalyzes the oxidative decarboxylation of L-malate to pyruvate and CO2. Transcription of the S. pombe malic enzyme gene, mae2, was studied to elucidate the regulatory mechanisms involved in the expression of the gene. No evidence for substrate-induced expression of mae2 was observed in the presence of 0.2% L-malate. However, transcription of mae2 was induced when cells were grown in high concentrations of glucose or under anaerobic conditions. The increased levels of malic enzyme may provide additional pyruvate or assist in maintaining the redox potential under fermentative conditions. Deletion and mutation analyses of the 5'-flanking region of the mae2 gene revealed the presence of three novel negative cis-acting elements, URS1, URS2, and URS3, that seem to function cooperatively to repress transcription of the mae2 gene. URS1 and URS2 are also present in the promoter region of the S. pombe malate transporter gene, suggesting co-regulation of their expression. Furthermore, two positive cis-acting elements in the mae2 promoter, UAS1 and UAS2, show homology with the DNA recognition sites of the cAMP-dependent transcription factors ADR1, AP-2, and ATF (activating transcription factor)/CREB (cAMP response element binding).

Anaerobiosis↗
PubMed1998

Mutation of Gly-444 inactivates the S. pombe malic enzyme.

A mutant malic enzyme gene, mae2-, was cloned from a strain of Schizosaccharomyces pombe that displayed almost no malic enzyme activity. Sequence analysis revealed only one codon-altering mutation, a guanine to adenine at nucleotide 1331, changing the glycine residue at position 444 to an aspartate residue. Gly-444 is located in Region H, previously identified as one of eight highly conserved regions in malic enzymes. We found that Gly-444 is absolutely conserved in 27 malic enzymes from various prokaryotic and eukaryotic sources, as well as in three bacterial malolactic enzymes investigated. The evolutionary conservation of Gly-444 suggests that this residue is important for enzymatic function.

Amino Acid Sequence↗
PubMed1997

Engineering pathways for malate degradation in Saccharomyces cerevisiae.

Deacidification of grape musts is crucial for the production of well-balanced wines, especially in colder regions of the world. The major acids in wine are tartaric and malic acid. Saccharomyces cerevisiae cannot degrade malic acid efficiently due to the lack of a malate transporter and the low substrate affinity of its malic enzyme. We have introduced efficient pathways for malate degradation in S. cerevisiae by cloning and expressing the Schizosaccharomyces pombe malate permease (mae1) gene with either the S. pombe malic enzyme (mae2) or Lactococcus lactis malolactic (mleS) gene in this yeast. Under aerobic conditions, the recombinant strain expressing the mae1 and mae2 genes efficiently degraded 8 g/L of malate in a glycerol-ethanol medium within 7 days. The recombinant malolactic strain of S. cerevisiae (mae1 and mleS genes) fermented 4.5 g/L of malate in a synthetic grape must within 4 days.

Bacterial Proteins↗
PubMed1997

The validity of melatonin as an oncostatic agent.

The validity of melatonin as a prominent, naturally occurring oncostatic agent is examined in terms of its putative oncostatic mechanism of action, the correlation between melatonin levels and neoplastic activity, and the outcome of therapeutically administered melatonin in clinical trials. Melatonin's mechanism of action is summarized in a brief analysis of its actions at the cellular level, its antioxidative functions, and its indirect immunostimulatory effects. The difficulties of interpreting melatonin levels as a diagnostic or prognostic aid in cancer is illustrated by referral to breast cancer, the most frequently studied neoplasm in trials regarding melatonin. Trials in which melatonin was used therapeutically are reviewed, i.e., early studies using melatonin alone, trials of melatonin in combination with interleukin-2, and controlled studies comparing routine therapy to therapy in combination with melatonin. A table compiling the studies in which melatonin was used in the treatment of cancer in humans is presented according to the type of neoplasm. Melatonin's suitability in combination chemotherapy, where it augments the anticancer effect of other chemotherapeutic drugs while decreasing some of the toxic side effects, is described. Based on the evidence derived from melatonin's antiproliferative, antioxidative, and immunostimulatory mechanisms of action, from its abnormal levels in cancer patients and from clinical trials in which melatonin was administered, it is concluded that melatonin could indeed be considered a physiological anticancer substance. Further well-controlled trials should, however, be performed in order to find the link between its observed effects and the underlying mechanisms of action and to define its significance as a therapeutic oncostatic agent.

Animals↗
PubMed1995

A kinase-cyclin pair in the RNA polymerase II holoenzyme.

The RNA polymerase II holoenzyme consists of RNA polymerase II, a subset of general transcription factors, and regulatory proteins known as SRB proteins. The genes encoding SRB proteins were isolated as suppressors of mutations in the RNA polymerase II carboxy-terminal domain (CTD). The CTD and SRB proteins have been implicated in the response to transcriptional regulators. We report here the isolation of two new SRB genes, SRB10 and SRB11, which encode kinase- and cyclin-like proteins, respectively. Genetic and biochemical evidence indicates that the SRB10 and SRB11 proteins form a kinase-cyclin pair in the holoenzyme. The SRB10/11 kinase is essential for a normal transcriptional response to galactose induction in vivo. Holoenzymes lacking SRB10/11 kinase function are strikingly deficient in CTD phosphorylation. Although defects in the kinase substantially affect transcription in vivo, purified holoenzymes lacking SRB10/11 kinase function do not show defects in defined in vitro transcription systems, suggesting that the factors necessary to elicit the regulatory role of the SRB10/11 kinase are missing in these systems. These results indicate that the SRB10/11 kinase is involved in CTD phosphorylation and suggest that this modification has a role in the response to transcriptional regulators in vivo.

Amino Acid Sequence↗
PubMed1995

Hemostatic competency and elastase-alpha 1-proteinase inhibitor levels in surgery, trauma, and sepsis.

Previous studies investigated the effects of neutrophil elastase on isolated factors in the hemostatic process. Some of these reported effects are, however, procoagulative and others anticoagulative. The aim of this study was to ascertain the effect of elastase on the in vivo hemostatic competency. The effect of elastase activity on the hemostatic competency was determined in a group of 50 surgical intensive care unit patients and 23 control subjects. Surgical intensive care unit patients were subgrouped into a surgery, a trauma, and a sepsis-multiple organ failure group. Elastase activity was assessed by elastase-alpha 1-proteinase inhibitor levels and hemostatic competency by thromboelastography. Thromboelastography results showed a relatively normal coagulative ability in the surgery group, a varying degree of thromboelastographic hypocoagulability in the trauma group, and pronounced thromboelastographic instability in the sepsis-multiple organ failure group. Increases in elastase-alpha 1-proteinase inhibitor levels up to 200 micrograms/L were accompanied by a compromised coagulative ability as seen in a prolongation of both the first and second phases of the clotting time, as well as a decrease in the maximal clot elasticity.

Case-Control Studies↗
PubMed1994

Molecular analysis of the malic enzyme gene (mae2) of Schizosaccharomyces pombe.

Sequence analysis of a 4.6-kb HindIII fragment containing the malic enzyme gene (mae2) of Schizosaccharomyces pombe, revealed the presence of an open reading frame of 1695 nucleotides, coding for a 565 amino acid polypeptide. The mae2 gene is expressed constitutively and encodes a single mRNA transcript of 2.0 kb. The mae2 gene was mapped on chromosome III by chromoblotting. The coding region and inferred amino acid sequence showed significant homology with 12 malic enzyme genes and proteins from widely different origins. Eight highly homologous regions were found in these malic enzymes, suggesting that they contain functionally conserved amino acid sequences that are indispensable for activity of malic enzymes. Two of these regions have previously been reported to be NAD- and NADP-binding sites.

Amino Acid Sequence↗
PubMed1994

[Computerization in intensive care].

Computers already constitute an integral part of intensive care units as almost all pieces of sophisticated equipment in intensive care contain a computerized component. However, a marked lack of computerization exists with regard to data collection, data analysis and in teaching support systems. This article presents a summary of the advantages of computerization of data in intensive care and cautions on possible pitfalls in the choice of equipment and in its implementation.

Hospital Information Systems↗
PubMed1992

Whole blood serotonin levels in chronic renal failure.

Whole blood serotonin levels were investigated in a control group (n = 35) and in a group of chronic renal failure patients (n = 127) on various treatment regimen i.e. conservative treatment (n = 39), maintenance haemodialysis (n = 35) and after renal transplantation (n = 53). The whole blood serotonin levels, as determined by high performance liquid chromatography, were significantly lower in the chronic renal failure patients than in the control group (p = 0.0001). Whole blood serotonin levels were significantly lower in the white subjects than in the black subjects of the study (p = 0.0001).

Adult↗
PubMed1992

Tripartite structure of the Saccharomyces cerevisiae arginase (CAR1) gene inducer-responsive upstream activation sequence.

Arginase (CAR1) gene expression in Saccharomyces cerevisiae is induced by arginine. The 5' regulatory region of CAR1 contains four separable regulatory elements--two inducer-independent upstream activation sequences (UASs) (UASC1 and UASC2), an inducer-dependent UAS (UASI), and an upstream repression sequence (URS1) which negatively regulates CAR1 and many other yeast genes. Here we demonstrate that three homologous DNA sequences originally reported to be present in the inducer-responsive UASI are in fact three exchangeable elements (UASI-A, UASI-B, and UASI-C). Although two of these elements, either the same or different ones, are required for transcriptional activation to occur, all three are required for maximal levels of induction. The elements operate in all orientations relative to one another and to the TATA sequence. All three UASI elements bind protein(s); protein binding does not require arginine or overproduction of any of the putative arginine pathway regulatory proteins. The UASI-protein complex was also observed even when extracts were derived from arg80/argRI or arg81/argRII deletion mutants. Similar sequences situated upstream of ARG5,6 and ARG3 and reported to negatively regulate their expression are able to functionally substitute for the CAR1 UASI elements and mediate reporter gene expression.

Arginase↗
PubMed1992

Melatonin in chronic renal failure.

The melatonin status of patients in end-stage chronic renal failure (CRF) was evaluated by the determination of daytime plasma melatonin levels and by the investigation of the circadian rhythmicity of melatonin secretion. A significant increase in plasma melatonin concentration was found in all CRF patient groups investigated, i.e. CRF patients on conservative treatment (CT; n = 48), CRF patients on maintenance haemodialysis treatment (HD; n = 39) and CRF patients on peritoneal dialysis (PD; n = 32). Successful transplantation led to a marked reduction in plasma melatonin levels. The circadian rhythm of melatonin secretion would appear to be suppressed in CRF as the nocturnal secretory surge was absent in all HD patients and in 80% of the posttransplantation patients studied.

Circadian Rhythm↗
PubMed1992

[The status of clinical evaluation at South African universities].

The fact that clinical evaluation is a difficult and complex task of nursing education has been emphasized in the nursing literature since the early seventies. It is, nevertheless, a most important component of the teaching-learning process of nursing students and it has definite advantages. It: contributes to the improvement of the standard of nursing care; helps to identify problem areas for research; and contributes to high level professional preparation. In the light of these factors the aims of the study were to: determine and describe the position of clinical evaluation as a component of the teaching of undergraduate students in departments of nursing at universities in Southern Africa; draw up a proto-theoretical model for clinical evaluation. The second aim will be fully discussed in a follow-up article. The empirical data showed that nursing educationists in Southern Africa are not entirely up to standard regarding the skills required for clinical evaluation.

Clinical Competence↗
PubMed1991

Physical properties of the red blood cells in chronic renal failure.

The biophysical properties of red blood cells in three groups of chronic renal failure (CRF) patients were compared to those of a non-renal control group. A limited number of biochemical and other parameters influencing the physical characteristics of red cells were also studied. Physical characteristics varied from normal to strikingly abnormal depending on the presence of factors other than CRF. Uraemia per se, in contrast to general belief, would appear not to be the major determinant of red cell survival in CRF.

Adult↗
PubMed1990

Unmet health care needs in the aged in two rural South African communities.

An evaluation of the unmet health care needs of all the aged people in two rural villages in the northern Transvaal was undertaken by assessing 7 indicators of health status to determine the prevalence of significant health problems and of receipt of health care for such problems. Oral health problems were found in 81% of the sample, visual problems in 62%, low peak expiratory flow in 48%, significant gastrointestinal symptoms in 38%, significant urinary symptoms in 32%, anaemia in 23%, and a lack of independence in 14%. There were 283 problems needing care, for which treatment had been received in the last year in only 30 instances (11%). The lack of care is attributed mainly to the inaccessibility of health services and the lack of health care resources in 'homeland' areas.

Black or African American↗
PubMed1987

[The heart].

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Arrhythmias, Cardiac↗