What is an anomaly?
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Congenital Abnormalities↗
Biomedical subjects
M Evans
Publications and source records attributed to M Evans.
Novel post-replicative DNA modification in Streptomyces: analysis of the preferred modification site of plasmid pIJ101.
Both Streptomyces lividans and Streptomyces avermitilis have the ability to site specifically modify their DNA, rendering it susceptible to in vitro Tris-dependent double-strand cleavage. We have cloned a 160 bp fragment containing the preferred modification site of plasmid pIJ101 and, employing an in vitro primer extension assay, determined that the modifications occur at guanine residues on either strand separated by 3 bp. These guanines are located within a 6 bp palindromic 'core' sequence. A cloned copy of a 35 bp region of the plasmid containing this core sequence was not recognized by the modifying activity in vivo. To further investigate the nature of the site specificity a set of deletion mutants of the 160 bp sequence were analysed. This revealed that a substantial portion of this sequence is essential for authentic modification. The essential region contains three 13 bp direct repeats, the central one containing the core sequence, while the left-hand and right-hand copies overlap two potential stem-loop structures. Deletion of either left- or right-hand repeat structures abolishes modification within the core sequence, although the left-hand deletion resulted in modification at a secondary site within the right-hand direct repeat. These data support a post-replicative mechanism of modification, underlined by the observation that the modifications are not detected in single-stranded plasmid replication intermediates.
Base Sequence↗
A combined analysis of genomic and primary protein structure defines the phylogenetic relationship of new members if the T-box family.
T-box genes form an ancient family of putative transcriptional regulators characterized by a region of homology to the DNA-binding domain of the murine Brachyury (T) gene product. This T-box domain is conserved from Caenorhabditis elegans to human, and mutations in T-box genes have been associated with developmental defects in Drosophila, zebrafish, mice, and humans. Here we report the identification of three novel murine T-box genes and an investigation of their evolutionary relationship to previously known family members by studying the genomic structure of the T-box. All T-box genes from nematodes to humans possess a characteristic central intron that presumably was inherited from a common ancestral precursor. Two additional intron positions are also conserved with the exception of two nematode T-box genes. Subsequent intron insertions, potential deletions, and/or intron sliding formed a structural basis for the divergence into distinct subfamilies and a substrate for length variations of the T-box domain. In mice, the 11 T-box genes known to date can be grouped into seven subfamilies. Genes assigned to the same subfamily by genomic structure show related expression patterns. We propose a model for the phylogenetic relationships within the gene family that provides a rationale for classifying new T-box genes and facilitates interspecific comparisons.
Amino Acid Sequence↗
Gender differences in autoimmune diseases: estrogen increases calcineurin expression in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) predominantly affects women (9:1 compared to men) of childbearing age and often decreases its intensity in postmenopausal women, suggesting that sex hormones play a role in its pathogenesis. Comparison of steady-state levels of calcineurin mRNA using RNase protection assays revealed increased calcineurin expression in response to estradiol in cultured T cells from nine female lupus patients. Calcineurin mRNA levels did not increase significantly in T cells from eight age-matched normal control female volunteers. Estrogen-dependent calcineurin mRNA increased in a dose-dependent fashion, while progesterone and dexamethasone did not increase calcineurin mRNA in patient cells. Lupus T cell calcineurin mRNA increased in response to estradiol at 6 h but not at 3 h. Calcineurin phosphatase activity increased in lupus T cell extracts after incubation of cells with estradiol, while phosphatase activity in normal T cells was unaffected by estrogen. Calcineurin expression in T cells from patients with vasculitis and rheumatoid arthritis taking medications similar to those taken by the lupus patients was unaffected by estradiol. This study provides the first evidence for a molecular marker of estrogen action in lupus patients and suggests that estrogen-dependent changes in lupus T cell calcineurin could alter proinflammatory cytokine gene regulation and T-B cell interactions.
Adult↗
Actinomycotic thyroiditis in a child.
The authors present a unique case of actinomycosis occurring in a 10-year-old girl who presented with a painless, noninflammatory left neck mass of 3 weeks duration. Physical examination findings showed a firm, nontender mass within the left thyroid lobe, and a presumptive diagnosis of thyroid neoplasm was made. Inflammatory changes subsequently occurred and surgical drainage was performed revealing sulphur granules. Histological examination confirmed actinomycosis of the thyroid gland.
Actinomycosis↗
Evaluation of criteria for chronic lung disease in surviving very low birth weight infants. Newborn Lung Project.
Criteria in common use for the diagnosis of chronic lung disease of prematurity or bronchopulmonary dysplasia in the neonatal period have not been sufficiently compared and validated against indicators of later respiratory complications. In this study of all 680 infants < or = 1500 gm birth weight admitted to six perinatal centers August 1, 1988, to July 31, 1990, 524 were alive and had no major congenital anomalies at 5 years old. Of 419 who had given permission to release their names and addresses, 272 were located and participated in a follow-up study. The following diagnostic criteria for bronchopulmonary dysplasia and chronic lung disease of prematurity were used during the initial hospitalization: (1) use of supplemental oxygen on day 30 of life, (2) a comprehensive bronchopulmonary dysplasia severity score applied at 25 to 35 days of life developed by a clinician panel to adjust for practice variation in ventilatory support and blood gases, (3) use of supplemental oxygen on day 30 of life with radiographic evidence consistent with bronchopulmonary dysplasia between days 25 and 35 of life, (4) radiographic evidence consistent with bronchopulmonary dysplasia alone, and (5) use of supplemental oxygen at 36 weeks' postconceptional age. These criteria were assessed against use of bronchodilators or steroids during the first 2 years of life, diagnosis of asthma, and hospitalizations for respiratory causes up to age 5. Although all criteria were significantly associated with all the outcomes, radiographic evidence was most predictive. These results indicate that, during a period when 21% of neonates were exposed to antenatal steroids, 24% received surfactant and 9% received postnatal corticosteroids, radiographic evidence was more predictive of long-term respiratory outcome than other commonly used criteria.
Bronchopulmonary Dysplasia↗
Massive hepatosplenomegaly, jaundice and pancytopenia in miliary tuberculosis.
A 29-year-old Caucasian woman presented to hospital with a 2-day history of diarrhoea, anorexia and rigors. Investigations showed abnormal liver function tests, hyponatremia, hypoalbuminaemia and lymphopenia. The initial chest radiograph was normal. A bone marrow trephine biopsy showed non-caseating granulomata and she subsequently developed miliary shadowing on the chest radiograph. A transjugular liver biopsy confirmed the presence of acid-alcohol fast bacilli. Despite starting triple therapy for miliary tuberculosis she remained febrile and developed massive hepatosplenomegaly, jaundice and pancytopenia. Standard triple therapy was substituted with ethambutol, streptomycin and oral prednisolone and the patient made a dramatic recovery. The clinical symptoms of miliary tuberculosis are frequently non-specific and the onset of the illness is often insidious. The liver is involved in almost all patients with miliary tuberculosis, but massive hepatosplenomegaly and jaundice are rare. Standard triple-therapy should be discontinued when there is significant liver dysfunction, and corticosteroids should be considered for patients with miliary tuberculosis who fail to respond to conventional therapy.
Adrenal Cortex Hormones↗
Measurement of impact force, simulation of fall and hip fracture.
It has been shown that the incidence of hip fracture in the elderly may be influenced by the type of floor covering commonly used in homes for the elderly. This study describes the development of a method for modelling a fall during a hip fracture event, to examine the influence of different floors on impact force. An impact transducer is dropped in free fall through a smooth plastic tube. The impactor nose of the transducer models the curvature of the greater trochanter, and a steel spring is used to simulate the compliance of the skeletal structure. A weight, which corresponds to one-sixteenth of average body mass, compresses the spring and applies force to the impactor nose on striking the floor. The temporal variation in the force of impact with the floor is measured by the transducer to within 0.41 percent (SD = 0.63%, n = 10). Five common floor coverings were tested over a concrete floor slab (vinyl, loop carpet and pile carpet--both with and without underpad). ANOVA analysis showed that the differences between mean forces for each floor covering were highly significant (p > 0.001), with the thicker coverings producing 7 percent lower forces. The transducer may be used to examine the correlation between impact force and fracture incidence for a variety of different floors in homes for the elderly.
Accidental Falls↗
Temporal variation of applied inter fragmentary displacement at a bone fracture in harmony with maturation of the fracture callus.
The amplitude of inter fragmentary displacement in long bone fractures greatly influences the pattern and speed of healing. Unfortunately, the amplitude of natural cyclical displacement arising from patient activity is random because of the inherent flexibility of fixation devices under natural loading. Although fixators may be designed to control the amplitude of this displacement, the amplitudes most beneficial to healing have not been determined. Furthermore, the appropriate amplitude must vary during healing as the reparative tissue (callus) progresses histologically and stiffens during maturation. In this study on an experimental fracture, the amplitude of applied cyclical displacement is varied during healing to correspond with the inverse of the callus stiffness versus time curve. In vivo mechanical stiffness tests on the callus indicate that the end point of the fixation period is achieved more rapidly than with a constant level of applied displacement.
Animals↗
Primary human osteoblast proliferation and prostaglandin E2 release in response to mechanical strain in vitro.
The application of mechanical loads to bone cells in vitro has been found to generate variable responses, which may in part be due to the source of the cell used and the characteristics of the strain applied. The aim of this study was to establish a system for applying well-defined physiological levels of mechanical strain to a well-defined population of human osteoblast-like cells. Human bone-derived cells obtained from the greater trochanter of the femur during total hip arthroplasty for osteoarthritis were cultured in the presence of 10 nmol/L dexamethasone and 100 mumol/L L-ascorbate-2-phosphate. Replicates of cells from each patient were loaded on separate occasions using controlled cyclical strains of 4000 microstrain (mu epsilon) or less. Strain gauges recorded reliable, reproducible strains between 1000 and 6000 mu epsilon. To establish reproducibility, sequential explant cultures derived from two patients were studied. A consistent increase (p < 0.05) in proliferation between replicates and explants derived from one patient subjected to 1600 mu epsilon on separate occasions was observed. Cells derived from sequential explants of the second patient showed no consistent increase in proliferation between replicates and explants. Three of six patients showed a significant increase (p < 0.05) in PGE2 production after 5 h in response to stretch (4000 mu epsilon) in all replicates on separate occasions, whereas, in the other three populations of cells, no increase in PGE2 was measured in any of the replicates. These results show that the application of highly controlled strains causes a significant effect on human bone cells, but only in a proportion of subjects. The response is consistent between sequential explants derived from the same patient. The implications of this study are that human osteoblast-like cells do respond to physiological strain in vitro, although some cells are more strain sensitive than others.
Anti-Inflammatory Agents↗
Association of tocolytic therapy with antenatal steroid administration and infant outcomes. Newborn Lung Project.
The use of tocolytic agents to halt premature labor is controversial. We examine a database on very low-birth-weight infants born following the onset of premature labor (n = 540) for association between tocolytic and antenatal steroid therapy, and to assess neonatal and childhood outcomes following combined therapy. Data are from a multicenter regionally based study of all infants below 1501 g at seven neonatal intensive care units (NICUs) in Wisconsin and Iowa, born August 1, 1988 through June 30, 1991. Infant outcomes analyzed are death in the first 30 days, respiratory distress syndrome (RDS), and intraventricular hemorrhage (IVH). Fewer deliveries occurred within 12 hours of labor onset with tocolytics (61 vs. 75% without). A strong association between tocolytic therapy and antenatal steroid administration was found [adjusted odds ratio OR = 5.7, 95% confidence interval CI: (3.3, 10.0)]. Tocolytics were associated with lower mortality in the first 30 days [OR = 0.29, CI: (0.15, 0.56)]. Joint administration of tocolytics and antenatal steroids versus neither was associated with lower incidence of the combined outcome of respiratory distress syndrome (RDS) or death [OR = .30, CI: (0.15, 0.60)] and grade III-IV IVH or death [OR = 0.35, CI: (0.14, 0.98)]. Tocolytic therapy alone was not associated with IVH grade III-IV [OR = 1.0, CI: (0.57, 1.9)] among survivors.
Cerebral Hemorrhage↗
Formative research in a school-based obesity prevention program for Native American school children (Pathways).
This paper describes how formative research was developed and implemented to produce obesity prevention interventions among school children in six different Native American nations that are part of the Pathways study. The formative assessment work presented here was unique in several ways: (1) it represents the first time formative research methods have been applied across multiple Native American tribes; (2) it is holistic, including data collection from parents, children, teachers, administrators and community leaders; and (3) it was developed by a multi-disciplinary group, including substantial input from Native American collaborators. The paper describes the process of developing the different units of the protocol, how data collection was implemented and how analyses were structured around the identification of risk behaviors. An emphasis is placed on describing which units of the formative assessment protocol were most effective and which were less effective.
Child↗
Regional differences in cerebral blood flow and glucose utilization in diabetic man: the effect of insulin.
To determine the effect of insulin on regional cerebral blood flow (rCBF) and glucose metabolism (CMRglu), we performed quantitative dynamic PET scanning of labeled water (H215O) and deoxyglucose (18FDG) using two protocols in 10 diabetic men. In protocol A, to test reproducibility of the technique, insulin was infused at 1.5 mU.kg-1.min-1 twice (n = 5). In protocol B, low (0.3 mU.kg-1.min-1) and high (3 mU.kg-1.min-1) dose insulin was given on separate occasions (n = 5). Euglycemia (5 mmol/L) was maintained by glucose infusion. In protocol A, CMRglu was 6% higher during the first infusion, and catecholamines were also increased, indicating stress. Blood flow was not different. Changing free insulin levels from 20.5 +/- 4.8 to 191 +/- 44.5 mU/L (P < 0.001, low versus high dose, protocol B) did not alter total or regional CMRglu (whole brain 36.6 +/- 4.0 versus 32.8 +/- 6.2 mumol.100 g-1.min-1, P = 0.32) or CBF (41.7 +/- 5.1 and 45.6 +/- 9.7 mL.100 g-1.min-1, P = 0.4) or rCBF. In cerebellum, CMRglu was lower than in cortex and the ratio between rate constants for glucose uptake and phosphorylation (K1 and k3) was reversed. There are regional differences in cerebral metabolic capacity that may explain why cerebral cortex is more sensitive to hypoglycemia than cerebellum. Brain glucose metabolism is not sensitive to insulin concentration within the physiologic range. This suggests that intracerebral insulin receptors have a different role from those in the periphery.
Adult↗
Therapy and clinical trials.
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Clinical Trials as Topic↗
Therapy and clinical trials.
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Clinical Trials as Topic↗
Combination of zolazepam and tiletamine as a sedative and anaesthetic for wombats.
OBJECTIVE: To assess the suitability of the combination of zolazepam and tiletamine for routine use as chemical restraint, sedative and anaesthetic in wild wombats. ANIMALS: Sixty common wombats, 25 southern hairy-nosed wombats and 40 northern hairy-nosed wombats. PROCEDURE: Wombats caught in cage-traps in the wild were given injections of the anaesthetic combination either intramuscularly or intraperitoneally. Anaesthesia was maintained for up to 4 h in some cases, and for 12 h in one case. All wombats were released after anaesthesia. RESULTS AND CONCLUSION: This drug combination is effective and apparently safe for the sedation or light anaesthesia of wombats. We did not observe adverse reactions or deaths and the dose range used (4 to 15 mg/kg) demonstrates a wide safety margin. The use of this anaesthetic combination was effective in reducing the stress to wombats from capture and handling.
Anesthetics, Combined↗
Carbohydrates as a cerebral metabolic fuel.
The human brain is an extremely active metabolic organ with little endogenous stores of energy. It is thus dependent on circulating glucose to fuel metabolism and support cognitive functioning. However there is growing evidence that the human brain is able to utilise other non-glucose fuels during times of glucose lack. We review the evidence for the potential of the human brain to use the alternate fuels lactate and beta-hydroxybutyrate, and some recent studies examining the ability of regions of brain to use non-glucose lipid fuels. The human brain does not seem to have the ability to use the gluconeogenic precursor alanine to any significant degree. Regionality within the brain can be examined in vivo by the use of positron emission tomography, which offers the exciting prospect of studying human brain metabolism in vivo using a simple and non-interventional technique. Increased understanding of the brain's metabolism, the way in which hypoglycaemia is recognised and the manner in which this can be altered in the syndrome of hypoglycaemia unawareness and deficient counterregulation will help develop further strategies to prevent the clinical problems associated with hypoglycaemia in insulin-dependent diabetic adults and children.
Adult↗