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Biomedical subjects

S Kerr

Publications and source records attributed to S Kerr.

At least 37 records · Page 2Linked to original sources
PubMed1998

Development and progression of microalbuminuria in a clinic sample of patients with insulin dependent diabetes mellitus.

The evolution of abnormal albumin excretion and its association with suggested risk factors were studied in 233 children with insulin dependent diabetes mellitus (IDDM) attending a single paediatric diabetic clinic over an eight year period. Yearly albumin:creatinine ratios (ACR; measured in mg/mmol) in early morning urine samples, glycated haemoglobin (HbA1c), and blood pressure were recorded. Thirty four (14.5%) children had a persistently raised ACR (ACR > or = 2.5 mg/mmol on at least three consecutive occasions) and 21 (9%) had an intermittently raised ACR (ACR > or = 2.5 mg/mmol on at least two occasions). Factors associated with a persistently raised ACR compared with normal albuminuria in IDDM included longer duration of diabetes, raised median HbA1c during the first five years after diagnosis, and final age adjusted systolic and diastolic blood pressure represented as standard deviation scores. The onset of persistently raised ACR in 13 of 34 children was before puberty and in 23 of 34 children it was within the first four years of diagnosis. The cross sectional prevalence of raised ACR was 12.9% at one year, 18.3% at five years, and 33% at 10 years after diagnosis. Raised ACR occurs frequently before puberty and in the early stages of childhood diabetes.

Age of Onset↗
PubMed1996

Degeneracy in human multicopy RBM (YRRM), a candidate spermatogenesis gene.

In order to search for mutations in the multicopy RBM genes that might be associated with male infertility, we have used sequence data from the reported cDNA clone to determine the intron exon boundaries of the YRRM 1 gene. This gene has 12 exons, three of which encode the putative RNA binding domain of the protein. Different copies of the gene contain sequence variations and, additionally, give rise to transcripts with different numbers of copies of the repeated SRGY motif. Since mutations in the RNA binding domain would seem likely to have an effect on the activity of the protein, we have scanned these exons for mutations by SSCP on DNA from normal and infertile men. Sequence differences in the exon encoding the N-terminal part of the RNA binding domain account for at least four different classes of the gene and give rise to different SSCP conformers. Sequence analysis shows that one of these classes is a pseudogene and that the members of another class are nonfunctional. RT-PCR shows that all classes are transcribed and that the A class is most abundant. We have found a point mutation that alters the highly conserved RNP2 motif in one infertile patient. This mutation is also found in his father. We have used PCR followed by SSCP analysis to map RBM on a Y Chromosome (Chr) YAC contig and have demonstrated a distribution that spans a major part of this chromosome's euchromatin.

Amino Acid Sequence↗
PubMed1996

A murine homologue of the human DAZ gene is autosomal and expressed only in male and female gonads.

We have isolated a homologue of the human Y linked DAZ (deleted in azoospermia) gene from mouse. This gene, Dazla (Daz like, autosomal), is autosomal, located on chromosome 17 and apparently single copy. The predicted protein is highly homologous to that encoded by the DAZ gene in the N-terminal regions of the two proteins and this homology is not confined to the RNA binding domain. Analysis of its expression pattern by reverse transcription PCR shows that the transcript is only detectable in male and female gonads and that testes lacking germ cells do not contain detectable amounts of transcript. We have been unable to detect a Y-linked DAZ homologue in mouse and our results point to the possibility of a role for autosomal RNA binding proteins in mammalian gametogenesis.

Amino Acid Sequence↗
PubMed1996

Population pharmacokinetics of caffeine in neonates and young infants.

The population pharmacokinetics of caffeine were investigated in 60 neonates and young infants using data collected during routine therapeutic drug monitoring. Clearance was influenced by body weight and postnatal age, and increased in the presence of dexamethasone. No clinical factors were identified that influenced volume of distribution. The population pharmacokinetic parameter estimates were then tested prospectively in a further 20 neonates. Although they produced unbiased results, the dexamethasone effect could not be identified. A final analysis using all 80 patients found clearance (L/day) = 0.14 x weight (kg) + 0.0024 x postnatal age (days) (+/- 20%) and volume of distribution = 0.82 L (+/- 24%). Simulations based on these results indicated that the current dosage guidelines of 20 mg/kg loading dose of caffeine citrate followed by a 5 mg/kg/day maintenance dose should achieve concentrations within the traditional target range in > 70% of neonates.

Administration, Oral↗
PubMed1995

Axonal injury: a universal consequence of fatal closed head injury?

beta-Amyloid precursor protein immunostaining has recently been shown to be a reliable method for detecting the damage to axons associated with fatal head injury. In an attempt to compare the efficacy of this technique with conventional histological detection of axonal damage, we have reanalysed sections from a large well-characterised series of head-injured and control patients. The results indicate that the frequency of axonal injury has been vastly underestimated using conventional silver techniques, and that axonal injury may in fact be an almost universal consequence of fatal head injury.

Adolescent↗
PubMed1995

Extracorporeal membrane oxygenation for the treatment of massive pulmonary embolism.

After witnessing the death of a patient following pulmonary embolectomy, John H. Gibbon, Jr, developed the idea of a device for extracorporeal oxygenation and circulation. What followed has led to the present-day method of extracorporeal membrane oxygenation as an effective method of cardiorespiratory support. In this case of massive acute pulmonary embolism, its use in a conscious patient completes the circle from the first ideas of Gibbon.

Acute Disease↗
PubMed1995

Physiology and behaviour of free-swimming Atlantic cod (Gadus morhua) facing fluctuating temperature conditions

Atlantic cod (Gadus morhua L.), acclimated to 5 °C, were equipped with ultrasonic transmitters which allowed the continuous monitoring of their vertical movements and heart rate. Fish were then placed in a 125 m3 tower tank in which the various thermal conditions they encounter in their natural environment were reproduced. Physiological and behavioural responses of cod were followed in parallel to the induced environmental changes. The experimental conditions studied in the tower tank were also reproduced in a swimming respirometer, where oxygen consumption and heart rate could be monitored within the activity range of a free-swimming animal. In a homogeneous water column, a rise in temperature induced marked increases in fish swimming activity, heart rate and heart beat-to-beat variability. In a thermally stratified environment, voluntary activity also increased when the thermal structure of the water column was altered, though no temperature-dependent changes in heart rate were observed. In this case, fish avoided the new temperature conditions, exhibiting distinct thermoregulatory behaviour. Stratification of the water column also prompted daily cyclic changes in fish distribution, animals tending to be in deeper and colder water layers during the day and in shallower and warmer layers at night. Respirometry experiments revealed that the thermoregulatory behaviour observed in free-ranging fish was probably driven by the energetic expedient of maintaining the physiological status quo ­ i.e. avoiding bioenergically costly reacclimation processes. Indeed, acute temperature increases or decreases of 2.5 °C led to marked differences in oxygen consumption, with metabolic rate changes of 15 and 30 %, respectively. The persistent linear relationship between heart rate and oxygen consumption allowed us to estimate, from the heart rate recorded in free-swimming fish, the entire range of metabolic responses that cod underwent voluntarily while experiencing a thermally stratified water column. The most profound metabolic effect, however, was observed with feeding, when oxygen consumption increased by as much as 80 %, resulting in an estimated 90 % reduction in their subsequent scope for activity.

Journal Article↗
PubMed1995

Physiology and behaviour of free-swimming Atlantic cod (Gadus morhua) facing fluctuating salinity and oxygenation conditions

1. Atlantic cod (Gadus morhua L.) acclimated to a temperature of 5 &deg;C and 30 salinity were equipped with ultrasonic transmitters which allowed continuous monitoring of their heart rate and their position in the water column. Fish were placed in a 125 m3 tower tank which permitted various environmentally relevant modifications of the salinity and oxygenation conditions. Cod physiological and behavioural responses were followed in parallel to the environmental manipulations. Some of the experimental conditions studied in the tower tank were also reproduced in a swimming respirometer where fish oxygen consumption and heart rate were monitored at various levels of activity. 2. Lowering salinity from 30 to 26 did not change resting oxygen consumption, but increased active oxygen consumption. 3. Lowering salinity from 30 to 26 increased heart rate over the whole range of swimming speeds except at maximum speed. 4. Lowering oxygen tension to 9 kPa decreased oxygen consumption over the whole range of swimming speeds and decreased resting heart rate. 5. Low salinity did not significantly affect the relationship between heart rate and oxygen consumption. 6. Low oxygen levels decreased the oxygen transported per heart beat. 7. In the tower tank, bursts of activity were associated with tachycardias. 8. In uniform conditions, fish swam more deeply during the day than at night. 9. After an exploratory period of approximately 6 h, fish chose to remain in a low-salinity upper layer of the tank. Thereafter, high salinities were avoided. Fish tended to select low salinities if a choice was provided. 10. Fish generally avoided zones of low oxygen (<9 kPa) but continued voluntarily to enter regions with values as low as 3.0 kPa for short excursions or if food was offered.

Journal Article↗
PubMed1995

Abundant expression of translation initiation factor EIF-4E in post-meiotic germ cells of the rat testis.

BACKGROUND: Eukaryotic translation initiation factor EIF-4E is a key component in the regulation of translational efficiency of MRNAs and its increased expression may accelerate cell growth and division. EIF-4E has the potential to transform rat embryo fibroblast cells by cooperation with v-Myc or adenovirus E1A. Our previous study showed that a variety of tumor cells examined exhibited elevated levels of eIF-4E gene expression. Thus it is thought that overexpression of EIF-4E can result in aberrant growth and cell transformation. EXPERIMENTAL DESIGN: To characterize rat EIF-4E, a clone containing rat eIF-4E cDNA was isolated from a rat testis cDNA library by screening with a synthetic probe prepared by the reverse transcription-polymerase chain reaction (RT-PCR) method. Based on the conserved nucleotide sequences between mouse and human eIF-4E cDNA, two oligonucleotide primers for RT-PCR were synthesized chemically. The cloned cDNA was sequenced and used as a probe for analysis of the expression level of eIF-4E mRNA in normal, differentiated rat tissues by Northern blot analysis. In situ hybridization analysis with digoxigenin-labeled antisense eIF-4E RNA as a probe was carried out to identify the eIF-4E-expressing sites in rat tissues. In addition, to analyse the phosphorylation level of EIF-4E, the proteins were fractionated from rat tissues by affinity column chromatography followed by isoelectric focusing (IEF)-gel electrophoresis. RESULTS: The nucleotide sequence of the eIF-4E cDNA is highly conserved in human, rat, and mouse. Extraordinarily elevated expression, more than 50-fold compared with that in the adult rat prostate, of eIF-4E was observed in testicular germ cells of rats of reproductive age, which was much greater than that in any tumor cell lines examined so far. The amount of EIF-4E fractionated from the adult rat testis was approximately 10 times higher than that from the adult rat liver. At least half of the purified testicular EIF-4E proteins were phosphorylated, a ratio similar to that in other rat tissues such as liver. In situ hybridization analysis demonstrated that elevated expression of eIF-4E mRNA was mainly observed in post-meiotic germ cells. CONCLUSIONS: Full activity of EIF-4E in translation requires the phosphorylation of the protein on a specific serine residue. Thus the elevated level of EIF-4E observed in the adult rat testis should be reflected in increase of the functional activity of EIF-4E. Based on the results of in situ hybridization analysis and characterization of EIF-4E, it was concluded that abundant EIF-4E in the testis may play an important role in spermatogenesis through translational regulation of stage-specific mRNAs during germ cell development.

Amino Acid Sequence↗
PubMed1994

Factors influencing the outcome and duration of removable appliance treatment.

The study models and records of 150 consecutively completed removable appliance cases were analysed and the influence of various factors assessed on both the change in Peer Assessment Rating (PAR) score produced by treatment and the duration of treatment. For the purpose of analysis the material was divided into two groups; a functional appliance/headgear group (n = 43) and an upper removable appliance group (n = 103). The initial PAR score accounted for 71 per cent of the variation in PAR change in the functional/headgear group when combined with the sex of the patient; females on average showing a further improvement of 3 PAR points over equivalent males. The initial PAR score alone accounted for 68 per cent of the variation in PAR change in the upper removable appliance group. Sixty per cent of the variability in treatment duration could be explained in the functional/headgear group by the initial PAR score and a binary variable indicating whether three or more appliances had been required. Fifty-six per cent of the variability in duration in the upper removable appliance group was explained by the number of appliances used alone. Regression equations for prediction of outcome and duration of removable appliance treatment are given.

Adolescent↗
PubMed1994

Angiocentric invasion by lentigo maligna melanoma.

A case of angiocentric invasion by a lentigo maligna melanoma is reported. Pericapillary cuffing and permeative intimal expansion of veins by melanoma without luminal tumour cell emboli, thrombosis, or vascular destruction were associated with a lentigo maligna melanoma on the face of a 93 year old woman. This unusual infiltrative pattern suggests a specific interaction between melanoma cells and perivascular connective tissue elements, and may imply expression by tumour cells of receptors for molecules in the intima of blood vessels and in pericapillary stroma.

Aged↗
PubMed1993

Influence of counterregulatory hormones, independently of hypoglycaemia, on cognitive function, warning symptoms and glucose kinetics.

1. To assess the influence of counterregulatory hormones, independently of neuroglycopaenia, on higher cerebral (cognitive) function, 'hypoglycaemic' warning symptoms and glucose kinetics, 10 healthy subjects participated in two hyperinsulinaemic (2 m-units min-1 kg-1) glucose clamp studies. After 100 min of euglycaemia (plasma glucose level 5 mmol/l), the plasma glucose level was either (a) maintained at 5 mmol/l for 120 min by glucose infusion with concomitant replacement of counterregulatory hormones (continuous infusions of glucagon, adrenaline, noradrenaline, cortisol and growth hormone) to mimic the hormonal milieu normally associated with hypoglycaemia (hormone infusion study) or (b) lowered to 2.8 mmol/l for 120 min (hypoglycaemia study). Assessments were made of cognitive function (P300 auditory evoked responses), symptoms (visual analogue scales) and glucose kinetics (3-[3H]glucose). 2. Hypoglycaemia was associated with an increase in all symptoms (facial flushing, palpitations, tingling, trembling, sweating, hunger, light-headedness and sleepiness, P < 0.01) and all subjects were aware that blood glucose levels had fallen. P300 evoked potential latency increased from 280 +/- 6 to 312 +/- 5 ms (mean +/- SEM, P < 0.01). In contrast, P300 latency and several individual symptoms (hunger, facial flushing, sweating and light-headedness) did not change from baseline during the hormone infusion study (P < 0.05 versus hypoglycaemia). Hepatic glucose production was lower (1.5 +/- 0.4 versus 2.3 +/- 0.3 mg min-1 kg-1, P < 0.05) and peripheral glucose uptake was higher (7.4 +/- 1.0 versus 5.6 +/- 0.6 mg min-1 kg-1, P < 0.01) during infusion of the hormones compared with during hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

A comparison of three salmonella antigen-capture ELISAs and culture for veterinary diagnostic specimens.

Three sandwich-ELISAs, two of which are commercially available (Tecra and Locate), and one developed at the Veterinary Sciences Division, Stormont and a 3-step culture protocol, were compared for the detection of salmonella in 1000 animal specimens. Eight hundred and fifty of these were new submissions and the remainder were frozen portions from specimens previously shown to contain salmonellas by culture. The incidence of ELISA false-negative and false-positive results was highest for the Stormont and Locate kits respectively although the differences in sensitivity and specificity between the three ELISAs was not statistically significant. On 16 occasions all ELISA methods indicated the presence of salmonellas when none were isolated by initial culture, eight of these specimens contained salmonellas when reinvestigated by culture.

Animals↗
PubMed1993

Smoking in diabetic teenagers.

The prevalence of smoking amongst a group of 77 diabetic teenagers aged 11-18 years attending two paediatric clinics was determined using a questionnaire and urine cotinine assay. Five individuals were identified as definite smokers with two further individuals being probable smokers, all of whom were aged 15 years or more. This low prevalence (9%) is in contrast to a 48% prevalence in a young adult diabetic clinic. Many diabetic teenagers appear to acquire a regular smoking habit after leaving the paediatric clinic so it is important that health education is targeted at this group.

Adolescent↗