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Biomedical subjects

T Coetzee

Publications and source records attributed to T Coetzee.

At least 19 recordsLinked to original sources
PubMed1998

Myelin galactolipids are essential for proper node of Ranvier formation in the CNS.

The vertebrate myelin sheath is greatly enriched in the galactolipids galactocerebroside (GalC) and sulfatide. Mice with a disruption in the gene that encodes the biosynthetic enzyme UDP-galactose:ceramide galactosyl transferase (CGT) are incapable of synthesizing these lipids yet form myelin sheaths that exhibit major and minor dense lines with spacing comparable to controls. These CGT mutant mice exhibit a severe tremor that is accompanied by hindlimb paralysis. Furthermore, electrophysiological studies reveal nerve conduction deficits in the spinal cord of these mutants. Here, using electron microscopic techniques, we demonstrate ultrastructural myelin abnormalities in the CNS that are consistent with the electrophysiological deficits. These abnormalities include altered nodal lengths, an abundance of heminodes, an absence of transverse bands, and the presence of reversed lateral loops. In contrast to the CNS, no ultrastructural abnormalities and only modest electrophysiological deficits were observed in the peripheral nervous system. Taken together, the data presented here indicate that GalC and sulfatide are essential in proper CNS node and paranode formation and that these lipids are important in ensuring proper axo-oligodendrocyte interactions.

Action Potentials↗
PubMed1997

Reciprocating gait orthosis powered with electrical muscle stimulation (RGO II). Part I: Performance evaluation of 70 paraplegic patients.

Seventy paraplegics were fitted with an improved Reciprocating Gait Orthosis powered with or without (low-level injury) electrical stimulation of the thigh muscles (RGO II) as a secondary rehabilitation phase after the acute period. The patients comprised a broad cross-section of the paraplegic population applying for medical services and varied in age from 16 to 55 years, time since injury ranging from less than 1 to 15 years, injury levels ranging from C-6/7 to T-11/12, and varying levels of spasticity, contractures, scoliosis and other related medical and physiologic problems. The success/failure ratio was dependent on the injury level, which was 1:1 for paraplegics with injury level at C-6/7; 1.67:1 for those with injury of T-1/3; and about 4:1 for paraplegics with injury level from T-3 to T-12. Lack of motivation and medical problems unrelated to the RGO II treatment were the primary reasons for failure. The duration of treatment (outpatient service three times per week) ranged from 2 to 48 weeks (mean: 16). Forty-one patients who completed the RGO II rehabilitation and were sent home with the orthosis for independent use (for at least 6 months and up to 3 years) were surveyed by a staff member for analysis of the meaning and impact of the RGO II on the patient's life and health, and potential problems. It was shown that 80.5% of the 41 patients were regular users and 19.5% were non-users. Thirty-eight of the 41 patients declined an offer to return the RGO II equipment for a full refund, while three patients were willing to return the orthosis. It was concluded that the RGO II is viable orthosis for restoring standing and limited walking in paraplegics while providing sufficient function, safety, and reliability. The most appropriate patients for the use of such an orthosis consist primarily of those with T-3 to T-12 injury level and good motivation, although highly selected patients with higher injury levels also can benefit from its use. Regular use of the RGO II, even for exercise only, had a general positive impact on the patients' health and outlook.

Adolescent↗
PubMed1996

Myelination in the absence of galactocerebroside and sulfatide: normal structure with abnormal function and regional instability.

The vertebrate nervous system is characterized by ensheathment of axons with myelin, a multilamellar membrane greatly enriched in the galactolipid galactocerebroside (GalC) and its sulfated derivative sulfatide. We have generated mice lacking the enzyme UDP-galactose:ceramide galactosyltransferase (CGT), which is required for GalC synthesis. CGT-deficient mice do not synthesize GalC or sulfatide but surprisingly form myelin containing glucocerebroside, a lipid not previously identified in myelin. Microscopic and morphometric analyses revealed myelin of normal ultrastructural appearance, except for slightly thinner sheaths in the ventral region of the spinal cord. Nevertheless, these mice exhibit severe generalized tremoring and mild ataxia, and electrophysiological analysis showed conduction deficits consistent with reduced insulative capacity of the myelin sheath. Moreover, with age, CGT-deficient mice develop progressive hindlimb paralysis and extensive vacuolation of the ventral region of the spinal cord. These results indicate that GalC and sulfatide play important roles in myelin function and stability.

Animals↗
PubMed1996

Molecular cloning, chromosomal mapping, and characterization of the mouse UDP-galactose:ceramide galactosyltransferase gene.

UDP-galactose:ceramide galactosyltransferase (CGT) (EC 2.4.1.62) catalyzes the final step in the synthesis of galactocerebroside, a glycosphingolipid characteristically abundant in myelin. In this report, we describe the isolation of genomic clones spanning the mouse CGT gene. The mouse CGT gene consists of six exons that span a minimum of 70 kb of DNA and that encode a 541 amino acid translation product with extensive sequence similarity to the rat CGT enzyme and to UDP-glucuronosyltransferases (UGT). The 5'-untranslated region of the mouse CGT gene is encoded by a separate exon located approximately 25 kb upstream of the first protein-encoding exon. Furthermore, the genomic organization of the five coding region exons of the mouse CGT gene resembles that of the human UGT1 and rat UGT2B1 genes. Finally, analysis of somatic cell hybrids by PCR and fluorescence in situ hybridization to metaphase chromosomes has localized the mouse CGT gene to chromosome 3, bands E3-F1.

Amino Acid Sequence↗
PubMed1995

Methodological issues in a disablement prevalence study: Mitchells Plain, South Africa.

The Mitchells Plain Disability Survey was undertaken primarily to expand a community-based rehabilitation programme in an underprivileged South African urban community. This descriptive survey used a proportional stratified random cluster sampling strategy (sample size 2424), with stratification by suburb and clusters consisting of 15 adjacent plots. A household screening questionnaire (based on the WHO disability questionnaire), identified people who reported health problems affecting their functional ability, while a second follow-up interview confirmed disablement status and obtained a medical, disablement and demographic profile of the disabled and ascertained their needs. This paper discusses different methodological issues related to the survey design and emphasizes the need for standardization of methods in the disablement field. Sampling issues include sample loss in a multi-staged data collection strategy as well as the non-independence of observations when sampling entire house- holds. The trade-off between studying disability across diagnostic, disablement and age categories, and wide confidence intervals for specific prevalence rates, is discussed. Because of the prohibitive costs validation of disablement status is often omitted in a low-budget project (as this one was), weakening the design of such studies. Even if the 'disabled' are correctly identified, the criteria for identifying respondents determine what type of disablement prevalence will be obtained, Different diagnoses reported on screening yielded different positive predictive values of disability--the most debilitating conditions yielding the highest proportion of disabled people. The quality of the data--evaluated through comparisons of initial and repeat screening interviews, and proxy and self-reporting--is described. There is a need for disability research to continue developing suitable methods for a wide range of purposes. One such is a 'good-enough' survey design which can be implemented rapidly, at relatively low cost, to yield useful results at local level.

Activities of Daily Living↗
PubMed1994

Escherichia coli proteins, including ribosomal protein S12, facilitate in vitro splicing of phage T4 introns by acting as RNA chaperones.

To address the effect of host proteins on the self-splicing properties of the group I introns of bacteriophage T4, we have purified an activity from Escherichia coli extracts that facilitates both trans- and cis-splicing of the T4 introns in vitro. The activity is attributable to a number of proteins, several of which are ribosomal proteins. Although these proteins have variable abilities to stimulate splicing, ribosomal protein S12 is the most effective. The activity mitigates the negative effects on splicing of the large internal open reading frames (ORFs) common to the T4 introns. In contrast to proteins shown previously to facilitate group I splicing, S12 does not bind strongly or specifically to the intron. Rather, S12 binds RNA with broad specificity and can also facilitate the action of a hammerhead ribozyme. Addition of S12 to unreactive trans-splicing precursors promoted splicing, suggesting that S12 can resolve misfolded RNAs. Furthermore, incubation with S12 followed by its proteolytic removal prior to the initiation of the splicing reaction still resulted in splicing enhancement. These results suggest that this protein facilitates splicing by acting as an RNA chaperone, promoting the assembly of the catalytically active tertiary structure of ribozymes.

Amino Acid Sequence↗
PubMed1990

Deletion-tolerance and trans-splicing of the bacteriophage T4 td intron. Analysis of the P6-L6a region.

Non-directed mutagenesis and phylogenetic comparison suggest that certain elements of the bacteriophage T4 td group Ia intron are dispensable to self-splicing. The L6-P6a-L6a region was identified as a potential non-essential element, and was removed by sequential deletions extending from the L6a loop toward the P6 pairing. Assays for splicing indicate that as long as the P6 pairing is maintained, the 1016 nucleotide td intron can be reduced to less than 250 nucleotides while maintaining function in vivo and in vitro. The P6 pairing appears to be essential for splicing while P6a is not. In addition, a spontaneous pseudorevertant of a splicing-defective deletion was isolated and shown to result from a single nucleotide change in the predicted L6a loop. This genetic suppressor mimics the ability of Mg2+ to reverse the phenotype of the deletion, suggesting that function is restored by structural stabilization of P6. The tolerance of this region to deletion prompted us to split the ribozyme core in L6a, to generate precursors that might function in trans. Indeed, the two half-molecules do associate to form a bimolecular complex that yields accurately ligated exons both in vitro and in vivo. The biological implications of these results, as well as the usefulness of trans-splicing for generating unprocessed precursors in vitro are discussed.

Base Sequence↗
PubMed1986

African swine fever. I. Morphological changes and virus replication in blood platelets of pigs infected with virulent haemadsorbing and non-haemadsorbing isolates.

Replicating and mature viral particles were detected with the transmission electron microscope in blood platelets of pigs infected with virulent haemadsorbing and non-haemadsorbing African swine fever virus isolates. Although platelet numbers decreased terminally in infected pigs, the most noticeable morphological damage to these cells apparent in the last 2 days of the disease included cytoplasmic swelling, vacuolation, fragmentation and loss of dense granules.

African Swine Fever↗
PubMed1982

Clinical anatomy and physiology of the spleen.

Knowledge of the anatomy and function of the spleen is essential for the assessment of its role in disease. Of particular importance is the contribution of the spleen to the immune response and defence against infection, and the need to preserve this by a more conservative approach to the management of the ruptured spleen. Information regarding the segmental blood supply is being reassessed for possible application in surgery, while other methods of protecting children from episodes of overwhelming infection following splenectomy are in the process of evaluation.

Adult↗
PubMed1982

The non-reproductive consequences of vasectomy.

Uncertainty exists regarding the immunological consequences of vasectomy and the long-term effects of the operation on the hormonal status, genital organs and tract of man. The information available from the literature is summarized. The evidence favours the safety of vasectomy in the human male.

Antibody Formation↗
PubMed1980

Clinical anatomy of the umbilicus.

The diagnostic value of the appearance of the umbilicus in a wide range of conditions is discussed. Umbilical sepsis, tumours, fistulas, developmental anomalies and hernias are described, and the embryology of related structures is outlined.

Abdominal Neoplasms↗