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Biomedical subjects

A Lawson

Publications and source records attributed to A Lawson.

At least 19 recordsLinked to original sources
PubMed2000

Evidence that translation of smooth muscle alpha-actin mRNA is delayed in the chick promyocardium until fusion of the bilateral heart-forming regions.

Heart development in the chick embryo proceeds from bilateral mesodermal primordia established during gastrulation. These primordia migrate to the midline and fuse into a single heart trough. During their migration as a cohesive sheet, the cells of the paired heart fields become epithelial and undergo cardiac differentiation, exhibiting organized myofibrils and rhythmic contractions near the time of their fusion. Between the stages of cardiomyoblast commitment and overt differentiation of cardiomyocytes, a significant time interval exists. Using a new riboprobe (usmaar) for whole-mount in situ hybridization in chick embryos, we report the earliest phases of smooth muscle alpha-actin (smaa) mRNA distribution during the precontractile developmental window. We show that ingressed heart-forming regions express smaa by the head-process stage (Hamburger and Hamilton stage 5). In addition, we used usmaar to study the formation and early morphogenesis of the heart. Consistent with fate mapping studies (Garcia-Martinez and Schoenwolf [1993] Dev. Biol. 159:706-719; Schoenwolf and Garcia-Martinez [1995] Cell Mol. Biol. Res. 41:233-240; Garcia-Martinez et al., in preparation), our results with this probe, combined with detailed histological and SEM analyses of the so-called cardiac crescent, demonstrate unequivocally that the heart arises from separated and paired heart rudiments, rather than from a single crescent-shaped rudiment (that is, prior to fusion of the paired heart rudiments to establish the straight-heart tube, the rostral midline of the cardiac crescent lacks mesodermal cells and consequently fails to label with usmaar). Smaa is also expressed in the splanchnic and somatic mesoderm, marking the earliest step in coelom formation. Consequently, we also used usmaar to describe formation of the pericardium. Finally, we provide evidence of a post-transcriptional level of control of smaa gene expression in the heart fields. Our results suggest that the expression of smaa may mark a primitive mesodermal state from which definitive cell types can be derived through inductive events.

Actins↗
PubMed1999

Programmed cell death and the morphogenesis of the hindbrain roof plate in the chick embryo.

The spatial and temporal distribution of apoptosis in the dorsal midline of the developing chick hindbrain was examined in relation to the development of the neuroepithelium and neural crest using scanning and transmission electron microscopy, immunocytochemistry and in situ hybridization. The pattern of TUNEL labeling and Slug expression in the dorsal midline at stages 10 and 11 differed from that at stages 12-15. At stages 10 and 11, TUNEL labeling and Slug expression were observed in the dorsal part of location II of rhombomere 1/2 (i.e., between the surface ectoderm and the neuroepithelium), but from stage 12 onward, they were observed in both the dorsal and ventral parts of location II. The implication is that whereas apoptosis may be restricted to a subpopulation of the early migrating neural crest at stages 10 and 11, it presumably occurs in subpopulations of both neural crest and neuroepithelial cells from stage 12 onward. Furthermore, as judged by the pattern of TUNEL labeling and Slug expression in r3 and r5, apoptosis in these two rhombomeres likely occurs in subpopulations of both neural crest and neuroepithelial cells. The eminence present in location I of r1/r2 between stages 10 and 12 consisted of both neural crest and neuroepithelial cells. These cells gradually underwent apoptosis until stage 12, when the eminence disappeared in most embryos. The formation of the inner (neuroepithelial) aspect of the hindbrain roof plate involved both cell migration from adjacent neuroepithelium and an alteration in the shapes of the cells, such that cells with flattened surfaces eventually lined the roof plate. During these processes, some of the neuroepithelial cells underwent apoptosis (i.e., in location IV). The results of this study thus demonstrate that subpopulations of both neuroepithelial and neural crest cells may be involved in programmed cell death in the hindbrain. Additionally, apoptosis in the hindbrain contributes significantly to morphogenetic thinning during roof plate formation.

Animals↗
PubMed1998

Neural fold fusion in the cranial region of the chick embryo.

Cranial neural fold fusion in the chick embryo is known to commence in the midbrain region before progressing cranially and caudally to involve the fore- and hindbrain regions, respectively. The two epithelial layers at the tips of the neural folds that participate in fusion are the surface ectoderm and the neuroepithelium. We have examined and compared cranial neural fold fusion in both layers, and our results show that fusion of the neuroepithelial component of the neural folds, unlike that of the surface ectoderm, starts in the caudal portion of the forebrain. Second, contrary to the widely accepted opinion, we have demonstrated that in the hindbrain region, fusion of the neuroepithelial component of the neural folds does not occur. Soon after neural fold apposition, a neuroepithelial eminence appears in rhombomeres 1 and 2, and this, together with other neuroepithelial cells in the dorsal midline of the hindbrain, undergoes massive apoptosis. The absence of neuroepithelial fusion in the hindbrain may be due to the presence of massive apoptosis among neuroepithelial cells that should have participated in the fusion process. The events described above may predispose the hindbrain to the development of neural tube defects. The appearance of cranial neural crest cells in the midline during their migration may enhance the fusion of the surface ectodermal portion of the neural folds.

Animals↗
PubMed1998

Surface ectodermal wound healing in the chick embryo.

Wound healing has been studied in the surface ectoderm overlying the midbrain region of stages 16-20 chick embryos by light microscopy, scanning and transmission electron microscopy, and immunofluorescent techniques. The embryos were divided into 6 groups, i.e. stages 16-17 for groups I, V and VI, and stages 19-20 for groups II, III and IV. For groups I and II embryos, a longitudinal incision about 0.6 mm was made close to the dorsal midline and the embryos incubated for varying periods of time up to 24 h. To determine the role of actin in the process of healing, selected groups I and II embryos were stained with FITC phalloidin and the wound margins examined using a confocal microscope. Wounds of all embryos in group I and about 20% in group II healed completely within 24 h of reincubation. The process of healing involved a change in the shapes of the ectodermal cells at the wound ends. This appeared as a zipping-up of the wound from both ends. In about 80% of group II embryos where healing did not occur, wound gaping was marked. Intense actin staining (actin cable) was observed at the wound margins of groups I and II embryos suggesting that the actin purse-string mechanism may play a role during wound healing in this epithelial model. The role of tension in wound healing was also determined by placing 2 secondary wounds about 0.5-0.7 mm long close to, and at right angles to the ends of the primary wound in groups III and V embryos. The procedure decreased the tension within the ectodermal cells at the wound ends. Groups IV and VI embryos served as controls for groups III and V embryos, respectively. Healing of both primary and secondary wounds after reduction of tension was rapid. Most primary wounds in group V embryos healed completely within 3 h of reincubation and the rate of reepithelialisation after the reduction of tension was about 160% more than that in group VI (control) embryos. Similarly, most primary wounds in group III embryos were almost closed within 6 h of reincubation. Here, the rate of reepithelialisation was 80 % more than that in group IV (controls). Thus tension is an important factor in wound healing in this model.

Animals↗
PubMed1997

Distinct signaling from stem cell factor and erythropoietin in HCD57 cells.

A recent report (Wu, H., Klingmuller, U., Besmer, P., and Lodish, H. F. (1995) Nature 377, 242-246) documents the interaction of the erythropoietin (EPO) receptor (EPOR) with the stem cell factor (SCF) receptor (c-KIT) and suggests that SCF acts through the EPOR. To elucidate the ability of SCF to affect the erythropoietin signaling pathway, we studied the effect of SCF on EPOR phosphorylation, SHC/ERK-1 activity, and cell proliferation and apoptosis in EPO-dependent HCD57 cells. Treatment of these cells with SCF resulted in phosphorylation of the EPOR. However, SCF-dependent phosphorylation of the EPOR did not initiate an EPO-like intracellular signal. SCF induced proliferation, SHC phosphorylation, and activation of ERK-1 but did not activate the JAK/STAT pathway. SCF stimulated SHC phosphorylation and ERK-1 activation independent of the EPOR in cells where the EPOR was down-regulated; the presence of the EPOR appeared to facilitate SCF activation of SHC and ERK-1. Furthermore, treatment of HCD57 cells with SCF increased cell number over a 3-day treatment, but apoptosis was observed in these cells. These data may illustrate two distinct pathways for erythroid cell proliferation and prevention of apoptosis in response to EPO, thereby providing a system to discriminate these intracellular signals.

Apoptosis↗
PubMed1997

Randomized placebo-controlled study of the effects of simvastatin on haemostatic variables, lipoproteins and free fatty acids. The Oxford Cholesterol Study Group.

The Oxford Cholesterol Study is a randomized placebo-controlled trial designed primarily to assess the effects of simvastatin on blood cholesterol levels and side-effects in preparation for a large, long-term trial of the effects of cholesterol-lowering drug therapy on mortality. At present there is only limited evidence from randomized comparisons of the effects of HMG-CoA reductase inhibitors, such as simvastatin, on thrombogenic, as distinct from atherogenic, pathways in coronary heart disease. The present sub-study was carried out to assess the effects of simvastatin on a range of haemostatic variables, as well as on free fatty acids and on lipoprotein fractions not studied in detail previously. At an average of about 2 years after starting study treatment, non-fasting blood samples were obtained from a sequential sample of 162 participants who had been randomly allocated to receive 40 mg (54 patients) or 20 mg (57 patients) daily simvastatin or matching placebo treatment (51 patients). Only patients who reported taking their study treatment and who were not known to be diabetic or to be taking some other lipid lowering treatment were to be included. The principal comparisons were to be of those allocated simvastatin (i.e. 20 and 40 mg doses combined) vs those allocated placebo. Among patients allocated simvastatin, marginally significant lower factor VII antigen levels (12.10% +/- 6.08 of standard; 2P < 0.05) and non-significantly lower factor VII coagulant activity (8.24% +/- 4.99 of standard) and fibrinogen concentrations (0.10 +/- 0.08 g. l-1) were observed. In contrast, plasminogen activator inhibitor activity was significantly higher (2.62 +/- 1.03 IU; 2P < 0.01) among patients allocated simvastatin. No significant differences were seen in the other haemostatic factors studied (e.g. prothrombin fragment 1.2, factor XII and C1 inhibitor). Total free fatty acid concentration was marginally significantly reduced (2P = 0.02) with simvastatin, but none of the reductions in individual free fatty acids was significant. Lipoprotein fractions were only measured among patients allocated 40 mg daily simvastatin or placebo. Compared with placebo, simvastatin produced significant decreases not only in LDL cholesterol (1.74 +/- 0.15 mmol.1(-1): 2P < 0.0001) but also in VLDL cholesterol (0.28 +/- 0.08 mmol.1(-1); 2P < 0.001) and IDL cholesterol (0.17 +/- 0.03 mmol.1(-1); 2P < 0.0001). There were also lower triglyceride levels associated with LDL (0.07 +/- 0.01 mmol.1(-1); 2P < 0.0001), IDL (0.03 +/- 0.01 mmol.1(-1); 2P < 0.01) and VLDL (0.27 +/- 0.14; 2P = 0.05). The effects of simvastatin on haemostatic variables appear to be far less marked than its lipid effects. Given the associations of haemostatic factors with coronary heart disease incidence, larger randomized comparisons of the HMG-CoA reductase inhibitors (and of the newer fibrates which may produce greater effects) are needed to provide more reliable estimates of the extent to which they influence these variables.

Adult↗
PubMed1997

Cisapride reduces neonatal postoperative ileus: randomised placebo controlled trial.

AIM: To assess the efficacy of cisapride in reducing ileus persisting to the tenth postoperative day after neonatal abdominal surgery. METHODS: A prospective, randomised, double blind trial comparing rectal cisapride (1.4-2.3 mg/kg/day) with placebo over seven days was undertaken in 33 neonates. RESULTS: Seven of 12 (58%) patients receiving placebo and eight of 11 (73%) receiving cisapride achieved a first sustained feed during treatment. Of those receiving cisapride, the first sustained feed occurred at 2.3 days (SEM 0.6) compared with 4.7 days (SEM 0.8) with placebo. By the seventh day the mean daily net enteral balance was 69 (SEM 18) ml/kg in the cisapride subgroup and 17 (SEM 8) ml/kg for those receiving placebo. Stool was passed on 6.3 (SEM 0.4) treatment days in the cisapride subgroup compared with 4.1 (SEM 1.0) treatment days in the placebo subgroup. CONCLUSION: Cisapride is effective in neonates with a prolonged ileus after abdominal surgery.

Administration, Rectal↗
PubMed1997

Audit of ascertainment of deaths to children born in Cumbria, UK, 1950-89 through the NHS central register.

STUDY OBJECTIVE: To evaluate the completeness of notification of deaths by the National Health Service Central Register (NHSCR) for England and Wales. DESIGN: Deaths for a birth cohort were ascertained through scanning the relevant volumes of NHSCR. Attempts were made to confirm these deaths and additional deaths were ascertained through searching local records. Logistic regression was used to investigate how the probability of a death being missed by NHSCR varied with the year of birth, age at death, sex, and social class. SETTING: Deaths up to the end of 1989 in the CA postal area among 264,046 children born between 1950 and 1989 to mothers living in Cumbria. RESULTS: NHSCR originally ascertained 4139 deaths; local searches confirmed 3338 (81%) of these and found an additional 342. Most deaths missed by the NHSCR were neonatal deaths in the 1950s and 1960s. In the 1950s, 31% of children who died in the neonatal period either were not entered on NHSCR or, if they were entered, there was no record of their death. For children born from 1970 onwards, ascertainment of deaths through NHSCR was over 99% complete. CONCLUSIONS: The NHSCR was started in 1948 for the administration of records of National Health Service patients. It seems that many babies who died soon after birth were not therefore recorded. In parallel with the increasing use of NHSCR for epidemiological purposes, there has been a substantial and continuing improvement in its clerical procedures since the mid 1960's.

Cause of Death↗
PubMed1997

Interexaminer agreement for applied kinesiology manual muscle testing.

Two trials of the interexaminer reliability of Applied Kinesiology manual testing were conducted. On the first trial three clinicians, each with greater than ten years of experience with muscle testing procedures, tested 32 healthy individuals to estimate their agreement on the strength or weakness of right and left piriformis and right and left hamstring muscles. Significant agreement between examiners was found for piriformis muscles, but little significant agreement was noted when hamstrings were tested. In a second study, the same three examiners tested 53 subjects for strength or weakness of the pectoralis and tensor fascia lata muscles bilaterally. Significant interjudge agreement was found for pectoralis muscles, but no significant concordance could be found when the tensor fascia lata was examined.

Fascia Lata↗
PubMed1996

Randomised placebo controlled trial of effect on mood of lowering cholesterol concentration. Oxford Cholesterol Study Group.

OBJECTIVE: To evaluate the effects on mood of a substantial and prolonged reduction in total cholesterol concentration. DESIGN: Randomised placebo controlled comparison of patients who had been allocated to receive simvastatin 20 mg or 40 mg daily versus those allocated matching placebo in a ratio of 2:1. Follow up at an average of 152 weeks after randomisation. SUBJECTS: Men and women aged between 40 and 75 years at entry with blood total cholesterol of 3.5 mmol/l or greater, who were considered to be at higher than average risk of coronary heart disease based on medical history. MAIN OUTCOME MEASURES: The shortened profile of mood states questionnaire, reported use of psychotropic medication, and symptoms possibly related to mood. RESULTS: Simvastatin reduced total cholesterol by 1.9 mmol/l (26.7%) at the time of follow up. Among all 621 patients randomised to simvastatin (414 patients) or placebo (207 patients) there were no significant differences in the use of psychotropic medication or in reports of symptoms possibly related to mood. Of these patients, 491 (334 simvastatin, 157 placebo) completed the mood questionnaire, and there were no significant differences between the treatment groups in total or subscale scores, even when patients with low baseline cholesterol concentrations or elderly subjects were considered separately. CONCLUSION: These results do not support the hypothesis that treatment to lower cholesterol concentration causes mood disturbance.

Adult↗
PubMed1996

Co-expression of human protein disulphide isomerase (PDI) can increase the yield of an antibody Fab' fragment expressed in Escherichia coli.

Secretion to the periplasm of Escherichia coli enables production of many eukaryotic extracellular proteins in a soluble form. The complex disulphide bond arrangement of such proteins is probably a major factor in determining the low yield of correctly folded product observed in many cases. Here we show that co-expression of human protein disulphide isomerase increased the yield of a monoclonal antibody Fab' fragment in the periplasm of E. coli.

Amino Acid Sequence↗
PubMed1996

The effect of embryonic cerebrospinal fluid pressure and morphogenetic brain expansion on wound healing in the midbrain of the chick embryo.

The role of increased cerebrospinal fluid pressure and morphogenetic brain expansion on midbrain wound healing was studied in chick embryos at stages 16-22. The embryos were divided into six groups as follows: group I (stages 16/17), group II (stages 18/19), group III (stages 20-22), group IV (stages 18/19), group V (stages 20-22) and group VI (stages 18/19). The mid-brains of embryos of groups I-III were wounded and the embryos re-incubated for varying periods up to 24 h. The neuroepithelial wounds of all group-I embryos healed completely within 24 h. However, complete healing was observed in only 25% of wounds in group II and 11.4% in group III by 24 h. To reduce cerebrospinal fluid pressure and thus slow down brain expansion, longitudinal wounds (about 0.8 mm long) were made in the hindbrain roof plate of group-IV and group-V embryos, and puncture wounds (0.1 mm in diameter) also in the hindbrain roof plate of group-VI embryos. This allowed cerebrospinal fluid to escape prior to wounding the midbrain. There was a significant increase in the proportion of group-IV and group-V embryos with completely healed midbrain neuroepithelial wounds (77.3% and 28.6% respectively). However, a comparison between groups II and VI embryos yielded no statistically significant difference in healing. Thus, increasing cerebrospinal fluid pressure and brain expansion adversely affect midbrain neuroepithelial wound healing.

Animals↗
PubMed1996

Absence of effects of prolonged simvastatin therapy on nocturnal sleep in a large randomized placebo-controlled study. Oxford Cholesterol Study Group.

1. It has been suggested that lipophilic HMG CoA reductase inhibitors, like lovastatin and simvastatin, may cause sleep disturbance. 2. Six hundred and twenty-one patients at increased risk of coronary heart disease were randomized in a single centre to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. To assess the effects of prolonged use of simvastatin on nocturnal sleep quality and duration, a sleep questionnaire was administered to 567 patients (95% of 595 survivors) at an average of 88 weeks (range: 44-129 weeks) after randomization. 3. The main outcome measures were sleep-related problems and use of sleep-enhancing medications reported during routine study follow-up visits, and responses to the sleep questionnaire about changes in sleep duration and about various sleep events during the preceding month. 4. No differences were observed between the treatment groups in the frequency of sleep-related problems reported, in the proportion of follow-up visits at which such problems were reported, or in the use of sleep-enhancing medications. The numbers who stopped study treatment were similar in the different treatment groups, and no patient stopped principally because of insomnia. In response to the sleep questionnaire, there were no significant differences between the treatment groups in reports of various sleep events during the preceding month, except that slightly fewer patients allocated simvastatin reported waking often. No differences in sleep duration were observed. 5. This placebo-controlled trial does not indicate any adverse effects of prolonged treatment with simvastatin on systematically sought measures of sleep disturbance.

Adult↗
PubMed1994

Three-year follow-up of the Oxford Cholesterol Study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study.

We report the results of a randomized single-centre study designed to assess the effects of simvastatin on blood lipids, blood biochemistry, haematology and other measures of safety and tolerability in preparation for a large-scale multicentre mortality study. Six hundred and twenty-one individuals considered to be at increased risk of coronary heart disease were randomized, following a 2-month placebo 'run-in' period, to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. Their mean age was 63 years, 85% were male, 62% had a history of prior myocardial infarction (MI), and the mean baseline total cholesterol was 7.0 mmol.l-1. Median follow-up in the present report is 3.4 years. Eight weeks after randomization, 40 mg daily simvastatin had reduced non-fasting total cholesterol by 29.2% +/- 1.1 (2.03 +/- 0.08 mmol.l-1) and 20 mg daily simvastatin had reduced it by 26.8% +/- 1.0 (1.87 +/- 0.07 mmol.l-1). Almost all of the difference in total cholesterol at 8 weeks was due to the reduction in LDL cholesterol (40.8% +/- 1.6 and 38.2% +/- 1.4 among patients allocated 40 mg and 20 mg of simvastatin daily respectively), but simvastatin also reduced triglycerides substantially (19.0% and 17.3%) and produced a small increase in HDL cholesterol (6.4% and 4.8%). These effects were largely sustained over the next 3 years, with 40 mg daily simvastatin producing a slightly greater reduction in total cholesterol at 3 years (25.7% +/- 1.9 reduction) than did 20 mg daily simvastatin (22.2% +/- 1.8). There were no differences between the treatment groups in the numbers of reports of 'possible adverse effects' of treatment or of a range of different symptoms or conditions (including those related to sleep or mood) recorded at regular clinic follow-up. Mean levels of alanine aminotransferase, aspartate aminotransferase and creatine kinase were slightly increased by treatment, but there were no significant differences between the treatment groups in the numbers of patients with significantly elevated levels. A slightly lower platelet count in the simvastatin group was the only haematological difference from placebo, with no difference in the numbers of patients with low platelet counts. In summary, the simvastatin regimens studied produced large sustained reductions in total cholesterol, LDL cholesterol and triglyceride and small increases in HDL cholesterol. They were well tolerated, with no evidence of serious side-effects during the first 3 years of this study.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Respiratory abnormalities in infants of substance-abusing mothers: role of prematurity.

It is a current hypothesis that maternal history of drug addiction during pregnancy and detection of drugs in the urine of the newborn are associated with increased incidence of apnea. To test this hypothesis, we reviewed polygraphic studies of respiration in two groups of infants who had been exposed in utero to cocaine (and other drugs). The first group was composed of 20 term infants (39.1 +/- 0.8 weeks gestation), and premature infants (35.4 +/- 0.8 weeks gestation). None of the infants were on methylxanthines. These infants were matched with 15 term and 15 preterm infants of similar gestational age. Variables studied were: heart rate, respiration, chest impedance pneumography, nasal airflow and oxygen saturation (pulse oximetry). Apnea indices for central and obstructive events of short and long duration as well as periodic breathing and oxygen saturation were obtained. Term drug-exposed infants had less central apnea and a higher rate of periodic breathing compared to term controls, whereas drug-exposed premature infants had more obstructive apnea and less periodic breathing compared to premature controls. These observed differences within groups were subtle and clinically insignificant. Other parameters studied were not different. When term and preterm infants were compared, preterm infants had significantly higher central apnea, obstructive apnea and periodic breathing rates. These differences appeared to be related to gestational age differences, not to drug exposure. There was no evidence that exposure to cocaine and other drugs actually inhibited respiration.

Adult↗