Biomedical subjects

A J Millar

Publications and source records attributed to A J Millar.

At least 37 records · Page 2Linked to original sources

PubMed2000

Functional independence of circadian clocks that regulate plant gene expression.

BACKGROUND: Circadian clocks regulate the gene expression, metabolism and behaviour of most eukaryotes, controlling an orderly succession of physiological processes that are synchronised with the environmental day/night cycle. Central circadian pacemakers that control animal behaviour are located in the brains of insects and rodents, but the location of such a pacemaker has not been determined in plants. Peripheral plant and animal tissues also maintain circadian rhythms when isolated in culture, indicating that these tissues contain circadian clocks. The degree of autonomy that the multiple, peripheral circadian clocks have in the intact organism is unclear. RESULTS: We used the bioluminescent luciferase reporter gene to monitor rhythmic expression from three promoters in transgenic Arabidopsis and tobacco plants. The rhythmic expression of a single gene could be set at up to three phases in different anatomical locations of a single plant, by applying light/dark treatments to restricted tissue areas. The initial phases were stably maintained after the entraining treatments ended, indicating that the circadian oscillators in intact plants are autonomous. This result held for all the vegetative plant organs and for promoters expressed in all major cell types. The rhythms of one organ were unaffected by entrainment of the rest of the plant, indicating that phase-resetting signals are also autonomous. CONCLUSIONS: Higher plants contain a spatial array of autonomous circadian clocks that regulate gene expression without a localised pacemaker. Circadian timing in plants might be less accurate but more flexible than the vertebrate circadian system.

Arabidopsis↗

PubMed2000

Clock proteins: turned over after hours?

Light sensitivity and the involvement of unstable proteins are key features of circadian clocks. Both photoreception and ubiquitin conjugation may be associated with nuclear regulators encoded by genes recently identified in Arabidopsis.

Arabidopsis↗

PubMed2000

How plants tell the time.

The components of the circadian system that have recently been discovered in plants share some characteristics with those from cyanobacterial, fungal and animal circadian clocks. Light input signals to the clock are contributed by multiple photoreceptors: some of these have now been shown to function specifically in response to light of defined wavelength and fluence rate. New reports of clock-controlled processes and genes are highlighting the importance of time management for plant development.

Arabidopsis↗

PubMed2000

Independent action of ELF3 and phyB to control hypocotyl elongation and flowering time.

Light regulates various aspects of plant growth, and the photoreceptor phytochrome B (phyB) mediates many responses to red light. In a screen for Arabidopsis mutants with phenotypes similar to those of phyB mutants, we isolated two new elf3 mutants. One has weaker morphological phenotypes than previously identified elf3 alleles, but still abolishes circadian rhythms under continuous light. Like phyB mutants, elf3 mutants have elongated hypocotyls and petioles, flower early, and have defects in the red light response. However, we found that elf3 mutations have an additive interaction with a phyB null mutation, with phyA or hy4 null mutations, or with a PHYB overexpression construct, and that an elf3 mutation does not prevent nuclear localization of phyB. These results suggest that either there is substantial redundancy in phyB and elf3 function, or the two genes regulate distinct signaling pathways.

Base Sequence↗

PubMed2000

Ten years of liver transplantation at Groote Schuur Hospital.

INTRODUCTION: Liver transplantation has evolved from an experimental procedure to being the treatment of choice for many patients with end-stage liver disease, and is performed on a routine basis in most major centres throughout the world. However, certain situations peculiar to developing countries have a major impact on liver transplant programmes in these countries. We present the results of the liver transplant programme in Cape Town. PATIENTS AND METHODS: All patients undergoing orthotopic liver transplantation at Groote Schuur Hospital and Red Cross War Memorial Children's Hospital were included in this report. Standard surgical techniques were used for procuring the donor liver, the recipient hepatectomy and the subsequent implantation of the liver. All patients received standardised peri-operative management; in particular, the immunosuppressive protocol consisted of cyclosporin, steroids and azathioprine. Since October 1988, 83 patients have undergone 89 orthotopic liver transplants. There were 44 adults and 39 children, the age range being from 6 months to 56 years. The commonest indications for hepatic transplantation in adults included cryptogenic cirrhosis, auto-immune hepatitis and primary sclerosing cholangitis. In children biliary atresia was the commonest cause of liver failure. RESULTS: Of the 81 patients transplanted, 50 are alive and well with follow-up ranging from 2 months to 9.5 years. The cumulative graft survival rate was 72% at 1 year and 61% at 5 years. Six patients have undergone re-transplantation and 4 patients have had combined liver/kidney transplants. De novo hepatitis due to hepatitis B virus (HBV) has occurred in 8 patients following transplantation. Subsequent investigation has shown that 5 of the donors of these livers were hepatitis B core antibody (HBcAb)-positive, while information on the remaining 3 was not available. Tuberculosis (TB) has been a significant problem in 4 patients, with 2 deaths precipitated by anti-TB drug-induced hepatitis. Post-transplant lymphoproliferative disorder was also responsible for significant postoperative morbidity. CONCLUSION: Orthotopic liver transplantation has been established at Groote Schuur Hospital as the treatment of choice for selected patients with chronic end-stage liver disease. However, hepatitis B and TB appear to present a problem. The particularly high prevalence of HBV carrier status in our donor population may necessitate the use of living donors in the future.

Adolescent↗

PubMed2000

History of liver transplantation at the University of Cape Town and Groote Schuur Hospital.

The liver transplant programme at Groote Schuur Hospital was born out of a rich history of experimental liver transplantation and an active liver clinic. Professor John Terblanche has played a key role in the initiation and success of the programme. In the first 10 years since October 1988, 41 adults have undergone liver transplantation. The cumulative graft survival rates at 1 and 5 years were 74% and 62% respectively.

History, 20th Century↗

PubMed2000

Liver transplantation in children--the Red Cross War Memorial Children's Hospital experience.

Liver transplantation for infants and children has been available in South Africa for more than a decade. Current concerns have shifted from an initial target of early post-transplant survival to quality of life in the long term. Since 1985, 175 infants and children have been assessed, with 104 accepted for transplantation. Fifty have had orthotopic liver transplants (OLTx), 48 (3 retransplants) in Cape Town and 2 abroad. Biliary atresia was the most frequent diagnosis (52%) followed by acute liver failure (ALF) (16%). Waiting list mortality has remained high (15%), particularly for the ALF group (50%). Thirty-four patients survive 1 month--14 years post-transplant. Early post OLTx mortality was low (7%) but late morbidity and mortality (23%) were mainly due to viral infection: de novo hepatitis B (5 patients, 2 deaths), EBV-related post-transplantation lymphoproliferative disease (PTLPD) (6 patients, 4 deaths) and CMV disease (9 patients, 4 deaths). Tuberculosis prophylaxis, required in 6 cases, resulted in major morbidity in 1. Hypertension requiring medication along with some compromise of renal function has been present in all but 2 patients. However, all those of school-going age (20) attend school normally and remain in good health and only 3 of the survivors have abnormal liver function tests. Successful liver transplantation is possible in a developing country with limited resources. Scarcity of virus-free donors (HBV and HIV) leading to waiting list mortality and infrequent retransplantation along with long-term consequences of immunosuppression (infection, lymphoma and renal toxicity) remain problems.

Child↗

PubMed1999

The circadian clock controls the expression pattern of the circadian input photoreceptor, phytochrome B.

Developmental and physiological responses are regulated by light throughout the entire life cycle of higher plants. To sense changes in the light environment, plants have developed various photoreceptors, including the red/far-red light-absorbing phytochromes and blue light-absorbing cryptochromes. A wide variety of physiological responses, including most light responses, also are modulated by circadian rhythms that are generated by an endogenous oscillator, the circadian clock. To provide information on local time, circadian clocks are synchronized and entrained by environmental time cues, of which light is among the most important. Light-driven entrainment of the Arabidopsis circadian clock has been shown to be mediated by phytochrome A (phyA), phytochrome B (phyB), and cryptochromes 1 and 2, thus affirming the roles of these photoreceptors as input regulators to the plant circadian clock. Here we show that the expression of PHYB::LUC reporter genes containing the promoter and 5' untranslated region of the tobacco NtPHYB1 or Arabidopsis AtPHYB genes fused to the luciferase (LUC) gene exhibit robust circadian oscillations in transgenic plants. We demonstrate that the abundance of PHYB RNA retains this circadian regulation and use a PHYB::Luc fusion protein to show that the rate of PHYB synthesis is also rhythmic. The abundance of bulk PHYB protein, however, exhibits only weak circadian rhythmicity, if any. These data suggest that photoreceptor gene expression patterns may be significant in the daily regulation of plant physiology and indicate an unexpectedly intimate relationship between the components of the input pathway and the putative circadian clock mechanism in higher plants.

Circadian Rhythm↗

PubMed1999

Circadian biology: clocks for the real world.

The circadian system of Neurospora crassa includes a molecular feedback loop that is entrainable by light. A recent study has shown that a second, elusive oscillator interacts with the feedback loop to drive output rhythms.

Animals↗

PubMed1999

Inhalation burns in children.

Survival from serious burns in children has improved substantially in recent years. Mortality is predominantly determined by the total body surface area burned and the often unrecognised inhalation injury. A retrospective review of 4,451 consecutive children with thermal injuries over a 10-year period was undertaken to determine the incidence, clinical presentation, and pathology of inhalation injury and its contribution to morbidity and mortality. Inhalation burns were diagnosed clinically and confirmed endoscopically and post-mortem in 97 (2.2%) children; 77 sustained fire burns (mean age 4 years) and 20 hot-water burns (mean age 18 months). The Moylan classification stratified them into upper-airway burns in 59 children, major-airway burns in 29, and parenchymal burns in 44. Major-airway burns were always seen in conjunction with either upper-airway or parenchymal injury. Stridor and acute progressive respiratory distress were the two main symptoms, the onset of which was occasionally delayed for up to 72 h. Endoscopy was most helpful in confirming the diagnosis and determining airway management. Endotracheal intubation was needed in more than 50% of children, usually for less than 5 days, and was converted to tracheostomy in only 6. Persistent laryngeal and tracheal damage was identified in 4. Secondary pneumonia occurred in 41.5% of children with fire burns and 55% with hot-water burns. Extensive surface burns, parenchymal injury, and secondary pneumonia all contributed to the significant mortality. Post-mortem findings corroborated clinical and endoscopic evidence. This study suggests that inhalation burns were often not recognised, could present late, and usually had significant consequences. Early clinical diagnosis, supported by endoscopic findings and appropriate management, is essential if the high morbidity and mortality amongst these children is to be improved.

Burns, Inhalation↗

PubMed1999

Intrahepatic fetus-in-fetu: a case report and review of the literature.

The authors report the third case since 1964 of fetus-in-fetu presenting at Red Cross Children's Hospital. A fetal liver abnormality was detected during routine antenatal ultrasound scan, and the postnatal diagnosis of an intrahepatic, multiple fetus-in-fetu was made with abdominal ultrasound scan, plain radiograph of the abdomen and computed tomography. The mass was removed surgically by hemihepatectomy when the patient was 4 months of age. Imaging and the macroscopic and microscopic appearances of the abnormality confirmed the diagnosis and amplified it to include an adjacent teratoma. Multiple small subcapsular and perimass vascular hamartomas were coincidentally discovered in the liver. Two of the 3 nodules within the amniotic-lined cavity of the intrahepatic mass individually comply with the accepted criteria for fetus-in-fetu, and the third nodule has the accepted features of a benign teratoma. The existence of multiple fetus-in-fetu and fetus-in-fetu combined with a teratoma, is recorded in the medical literature. The imaging as well as the macroscopic and microscopic features are illustrated.

Female↗

PubMed1999

The use of diverting colostomies in paediatric peri-anal burns.

Over a 3 yr period we performed colostomies in 13 paediatric perineal burn patients out of a total of 1544 patients admitted to our Burns Unit during that period. The mean total body surface area (TBSA) burn was 34% (14-65%); ten patients sustained fire burns and the remaining three hot water burns. We performed prophylactic colostomies in seven children, therapeutic colostomies (to counteract deep wound infection and septicaemia with gut-derived organisms) in five patients and one colostomy in a cerebral palsy child with a left hemiparesis. A sigmoid end-colostomy with Hartmann's closure of the distal segment was the preferred method of choice. In all children but one (died from multi-organ failure 13 days after admission) there was a marked improvement in the clinical appearance of the burn wounds and subsequent graft-take and healing. There was a change in the bacterial profile away from predominantly gut-derived Gram negative organisms to either Pseudomonas aeruginosa or no pathological organisms grown. Complications were few--two children suffered prolapse of their colostomy requiring manual reduction. We advocate diverting colostomies in a highly select group of paediatric burn patients in whom continual faecal soiling is threatening to both graft and life.

Adolescent↗

PubMed1999

Circadian dysfunction causes aberrant hypocotyl elongation patterns in Arabidopsis.

Many endogenous and environmental signals control seedling growth, including several phototransduction pathways. We demonstrate that the circadian clock controls the elongation of the Arabidopsis hypocotyl immediately upon germination. The pattern of hypocotyl elongation in constant light includes a daily growth arrest spanning subjective dawn and an interval of rapid growth at subjective dusk. Maximal hypocotyl growth coincides with the phase during which the cotyledons are raised, in the previously described rhythm of cotyledon movement. The rhythm of hypocotyl elongation was entrained by light-dark cycles applied to the imbibed seed and its period was shortened in the toc1-1 mutant, indicating that it is controlled by a similar circadian system to other rhythmic markers. The daily groth arrest is abolished by the early flowering 3 (elf3) mutation, suggesting that this defect may cause its long-hypocotyl phenotype. Mutations that affect the circadian system can therefore cause gross morphological phenotypes, not because the wild-type gene functions pleiotropically in several signalling pathways, but rather because the circadian clock exerts wide-spread control over plant physiology.

Arabidopsis↗

PubMed1999

Natural allelic variation identifies new genes in the Arabidopsis circadian system.

We have analysed the circadian rhythm of Arabidopsis thaliana leaf movements in the accession Cvi from the Cape Verde Islands, and in the commonly used laboratory strains Columbia (Col) and Landsberg (erecta) (Ler), which originated in Northern Europe. The parental lines have similar rhythmic periods, but the progeny of crosses among them reveal extensive variation for this trait. An analysis of 48 Ler/Cvi recombinant inbred lines (RILs) and a further 30 Ler/Col RILs allowed us to locate four putative quantitative trait loci (QTLs) that control the period of the circadian clock. Near-isogenic lines (NILs) that contain a QTL in a small, defined chromo- somal region allowed us to confirm the phenotypic effect and to map the positions of three period QTLs, designated ESPRESSO, NON TROPPO and RALENTANDO. Quantitative trait loci at the locations of RALENTANDO and of a fourth QTL, ANDANTE, were identified in both Ler/Cvi and Ler/Col RIL populations. Some QTLs for circadian period are closely linked to loci that control flowering time, including FLC. We show that flc mutations shorten the circadian period such that the known allelic variation in the MADS-box gene FLC can account for the ANDANTE QTL. The QTLs ESPRESSO and RALENTANDO identify new genes that regulate the Arabidopsis circadian system in nature, one of which may be the flowering-time gene GIGANTEA.

Alleles↗

PubMed1999

Perianal candidosis--a comparative study with mupirocin and nystatin.

OBJECTIVE: To assess the efficacy and clinical outcome of 2% mupirocin in a polyethylene glycol base and nystatin cream as treatment regimens in diaper candidosis. DESIGN: A prospective randomized comparative study. METHODS: In vitro. The susceptibility of 20 clinical isolates of Candida albicans to 2% mupirocin, nystatin, and five additional antifungal agents was evaluated using the Nathan agar-well diffusion assay. The minimum inhibitory concentration (MIC) of mupirocin against the Candida species was determined using a tube dilution method. In vivo. Twenty patients (mean age, 12 months; range, 1 month to 4 years) with moderate to severe Monilia diaper dermatitis either had mupirocin ointment or nystatin cream applied to the infected area every 8 h or after every diaper change for a period of 7 days. Microscopic examination of skin scrapings and mycologic and microbiological cultures were performed before treatment and daily for 7 days, and progress was clinically assessed. RESULTS: In vitro. Topical mupirocin produced a greater zone of inhibition than nystatin cream, i.e. a mean of 27.2 mm (SD 1.55) compared with a mean of 17.3 mm (SD 1.08) for nystatin cream. MIC for mupirocin of 512 microg/mL in one case, 256 microg/mL in six cases, 200 microg/mL in 10 cases and 400 microg/mL in three cases were obtained for the 20 clinical isolates. C. albicans also displayed a universal sensitivity to mupirocin and nystatin. In vivo. Eradication of all Candida organisms was achieved within 2-6 days (mean, 2.6 days) in 10 patients receiving topical mupirocin therapy with rapid healing of the excoriated wounds (mean, 4.7 days). Both Gram-positive and Gram-negative bacteria were eradicated from the infected area within the trial period. Ten patients received topical nystatin cream and, in each case, Candida was successfully cleared within 5 days (mean, 2.8 days). Only three wounds were clinically healed within the trial period, however. The remaining seven wounds showed evidence of improved, but ongoing excoriated dermatitis and a heavy growth of polymicrobial organisms. CONCLUSIONS: Both agents eradicated Candida, the major difference being the marked response of the diaper dermatitis to mupirocin. Mupirocin should be applied topically 3-4 times daily or with each diaper change and is an excellent antifungal agent.

Administration, Topical↗

PubMed1999

Neonatal Soave endorectal pull-through for Hirschsprung's disease.

In October 1994 we changed our management of neonatal Hirschsprung's disease from a staged procedure after initial colostomy to a neonatal single-stage Soave endorectal pull-through (SERPT) without a colostomy. We report on our experience with the first 12 neonatal SERPTs, comparing them retrospectively with a consecutive series of 12 patients managed with initial colostomy, followed by a SERPT months later. A neonatal SERPT proved to be an easier and quicker procedure than the same procedure in the older child. Patients could be discharged earlier and fewer complications were encountered; in addition a colostomy was avoided. The cosmetic result and parental acceptance were excellent. At the same time the cost was less than half compared with the staged group. At this stage of follow-up functional results are comparable with previous staged pull-through procedures.

Anastomosis, Surgical↗

PubMed1998

Oesophageal replacement in the management of corrosive strictures: when is surgery indicated?

The accidental ingestion of corrosive agents is a major cause of oesophageal strictures in children. The mainstay of treatment is repeated dilatations. Despite this, a significant number of patients eventually require oesophageal bypass. We reviewed the records of all cases managed with this condition at the University of Cape Town teaching hospitals between 1976 and 1994. Dilatation therapy alone was successful in 14 out of 39 patients (41%). Morbidity of failed dilatation therapy included repeated hospital admissions over an average 11.5 months and 17 dilatations each. Oesophageal perforations occurred in 7 cases (18%). Early factors predictive of failure of conservative treatment were: delay in presentation of more than 1 month; severe pharyngo-oesophageal burns requiring a tracheostomy; oesophageal perforation; and a stricture longer than 5 cm on radiological assessment. The size of dilators accepted during early bougienage also correlated with eventual outcome. These criteria may be useful in predicting which patients will not respond to repeated dilatations. Early surgical intervention in such cases will prevent fruitless dilatations and related complications.

Acids↗

PubMed1998

An Arabidopsis mutant hypersensitive to red and far-red light signals.

A new mutant called psi2 (for phytochrome signaling) was isolated by screening for elevated activity of a chlorophyll a/b binding protein-luciferase (CAB2-LUC) transgene in Arabidopsis. This mutant exhibited hypersensitive induction of CAB1, CAB2, and the small subunit of ribulose-1,5-bisphosphate carboxylase (RBCS) promoters in the very low fluence range of red light and a hypersensitive response in hypocotyl growth in continuous red light of higher fluences. In addition, at high- but not low-light fluence rates, the mutant showed light-dependent superinduction of the pathogen-related protein gene PR-1a and developed spontaneous necrotic lesions in the absence of any pathogen. Expression of genes responding to various hormone and environmental stress pathways in the mutant was not significantly different from that of the wild type. Analysis of double mutants demonstrated that the effects of the psi2 mutation are dependent on both phytochromes phyA and phyB. The mutation is recessive and maps to the bottom of chromosome 5. Together, our results suggest that PSI2 specifically and negatively regulates both phyA and phyB phototransduction pathways. The induction of cell death by deregulated signaling pathways observed in psi2 is reminiscent of retinal degenerative diseases in animals and humans.

Arabidopsis↗