Biomedical subjects

M Morris

Publications and source records attributed to M Morris.

At least 19 recordsLinked to original sources

PubMed2007

Differential regulation of human YY1 and caspase 7 promoters by prohibitin through E2F1 and p53 binding sites.

Prohibitin is a 30 kDa growth suppressive protein that has pleiotropic functions in the cell. Although prohibitin has been demonstrated to have potent transcriptional regulatory functions, it has also been proposed to facilitate protein folding in the mitochondria and promote cell migration in association with Raf-1. Our previous studies have shown that prohibitin physically interacts with the marked-box domain of E2F family members and represses their transcriptional activity; in contrast, prohibitin could bind to and enhance the transcriptional activity of p53. Here, we show that promoters of human YY1 (Yin and Yang 1) as well as caspase 7 genes are modulated by prohibitin. YY1 promoter activity was reduced upon overexpression of prohibitin, while it was enhanced when prohibitin was depleted by small interfering RNA techniques. The repressive effects of prohibitin on the YY1 promoter were mediated through E2F binding sites, as seen by mutational analysis and chromatin immunoprecipitation assays. Further, depletion of E2F1 prevented prohibitin from repressing the YY1 promoter. In contrast with YY1, prohibitin overexpression led to enhanced levels of caspase 7, whereas depletion of prohibitin reduced it. Interestingly, the caspase 7 promoter was found to have p53-binding sites and prohibitin activated this promoter through p53. These studies show that prohibitin can have diverse effects on the expression of different genes and the activity of various cellular promoters is affected by prohibitin. Further, it appears very likely that prohibitin carries out many of its cellular functions by affecting the transcription of different genes.

Caspase 7↗

PubMed2006

Locus coeruleus lesions decrease oxytocin and vasopressin release induced by hemorrhage.

The role of the noradrenergic nucleus Locus Coeruleus (LC) on hemorrhage-induced vasopressin (AVP) and oxytocin (OT) secretion was examined. Rats with LC lesion were submitted to three 1-min hemorrhage sessions at 5-min intervals; 15% of the total blood volume was withdrawn in each session. OT and AVP were measured in plasma, paraventricular (PVN) and supraoptic (SON) nuclei and in posterior pituitary (PP). LC Lesion did not affect basal plasma AVP or OT levels, but partly blocked the increase in plasma AVP and OT induced by hemorrhage. Hemorrhage produced decreases in content of AVP and OT in the PVN and SON and increased levels in the PP. These responses were attenuated in the lesioned group, but only in the PVN and PP. Data suggest a stimulatory role of the inputs from LC to PVN neurons on hemorrhage-induced OT and AVP secretion and that, this pathway is critical in the hypo-volemic neuroendocrine reflex.

Animals↗

PubMed2006

Population-based study of prognostic factors in stage II colonic cancer.

BACKGROUND: Adjuvant chemotherapy in stage II colorectal cancer may be considered for patients whose tumours have poor prognostic features. The aim of this study was to evaluate the prognostic significance of commonly reported clinical and pathological features of stage II colonic cancer. METHODS: A population-based observational study of all patients with stage II colonic cancer diagnosed in the state of Western Australia from 1993 to 2003 was performed. A total of 1306 patients treated by surgery alone were identified, with a median follow-up of 59 (range 0-145) months. RESULTS: Multivariable analysis revealed that the only independent prognostic factors for disease-specific survival were stage T4 (hazard ratio (HR) 1.75 (95 per cent confidence interval (c.i.) 1.32 to 2.32); P < 0.001) and vascular invasion (HR 1.63 (95 per cent c.i. 1.15 to 2.30); P < 0.001). In younger patients (aged 75 years or less), who are more likely to be considered for chemotherapy, these two features showed independent prognostic significance but with higher HR values (1.96 for stage T4 and 2.73 for vascular invasion). Stage T4 and/or the presence of vascular invasion identified a 'poor' prognostic group, comprising 26.6 per cent of younger patients and with a 5-year survival rate of 71.2 per cent. The remaining 'good' prognostic group had a survival rate of 84.3 per cent at 5 years' follow-up. CONCLUSION: This study highlights the importance of accurate pathological assessment of tumour stage and vascular invasion for the prognostic stratification of patients with stage II colonic cancer. The results provide clarification of guidelines for the management of stage II disease in relation to recommendations for chemotherapy.

Adolescent↗

PubMed2006

Defining spatial parameters for non-linear walking.

Current definitions of the spatial and temporal parameters of gait have been based on the premise that walking occurs in a straight line. When the direction of progression (DoP) is not consistent and walking is non-linear, these definitions do not provide meaningful information. An alternative method based on the changing direction of each stride is presented. This method is easy to understand and use, and requires no expensive technology. A comparison of the spatial parameters of the footstep pattern during linear trials and trials incorporating a 60 degrees turn was performed, using output derived from the old and the new definitions. The two methods produced very different results. Spatial output from the old definitions was merely dictated by the change of direction. Output calculated relative to the changing stride direction however, provided useful information about the footstep adjustments made for turning and how these would act to improve stability. This method of establishing spatial parameters during non-linear walking should form a useful tool for further investigation of functional locomotion.

Biomechanical Phenomena↗

PubMed2006

Tinted contact lenses as an alternative management for photophobia in stationary cone dystrophies in children.

BACKGROUND: Intense photophobia is a debilitating symptom of the stationary cone dystrophies. The dark-tinted glasses with side-shields and floppy hats used to manage this are very conspicuous and can cause marked psychological morbidity to the children and their families. We assess the use of tinted contact lenses as an alternative management for the photophobia. METHODS: Three children, aged 5 to 13, with cone dystrophies, all with markedly reduced visual acuity, color vision, and profound photophobia were fitted with Lunelle ES70 Solaire 70% brown contact lenses. The child's parents completed two Children's Visual Function Questionnaires, the first pertaining to the period when the child wore tinted glasses; the second pertaining to the period of tinted contact lens wear. RESULTS: Subjectively, two of the children and their parents described a striking improvement in their quality of life, with improved confidence, interactions with other children, and cessation of name-calling and bullying. The Children's Visual Function Questionnaires gave objective evidence for this improvement in one child and was not significantly different in the other. The third child was reluctant to wear the contact lenses despite her parents' active encouragement. CONCLUSION: Tinted contact lenses offer an alternative management of the photophobia associated with stationary cone dystrophies in children. Marked improvements in their quality of life were observed in this case series.

Adolescent↗

PubMed2006

The psychosocial benefits of corrective surgery for adults with strabismus.

BACKGROUND: Few papers have addressed the psychological impact of strabismus in adults, with none comparing preoperative and postoperative data using standardised questionnaires relating surgical results and psychosocial outcomes. METHODS: 46 participants were seen at their 6 week preoperative and 3 month postoperative appointments. Standardised measures of anxiety and depression (Hospital Anxiety and Depression Scale), social anxiety (Derriford Appearance Scale), and quality of life (WHOQoLBref) were completed. RESULTS: Preoperatively, levels of depression were comparable to relevant population norms; however, levels of general anxiety were slightly raised and levels of social anxiety and social avoidance were significantly poorer than population norms. Surgery resulted in significant improvements in psychosocial adjustment with improvements on all study variables for the participant group as a whole. The non-diplopic group made more significant gains than the diplopic group. Approximately one third of study measures were significantly correlated with the objective measure of eye misalignment preoperatively dropping to only one variable postoperatively. Calculations involving the subjective measure of eye misalignment and study variables showed the opposite pattern with five variables achieving significance postoperatively. There were no clear sex or age effects apparent in the data. CONCLUSION: Strabismus surgery offers significant improvements to psychological and physical functioning.

Adolescent↗

PubMed2006

Acetylcholinesterase inhibition affects cardiovascular structure in mice.

Experiments were performed in C57BL/6J male mice to determine the effects of acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB) and stress on cardiovascular function, structure, and apoptosis. Mice were studied for seven days under the following conditions: Controls (osmotic minipump with saline), PB (10 mg/kg/day, minipumps), shaker stress (45 stressors/day, minipump with saline) and PB+Stress combination. AChE activity was significantly reduced in all PB-treated mice. PB caused no changes in 24-h mean arterial pressure (MAP) or heart rate (HR). Stress increased 24-h MAP on day 1 and 24-h HR on day 7 in both Stress and PB+Stress groups. A significant reduction in the aortic wall thickness/diameter ratio (P <0.05 vs. control) and slightly reduced relative heart weight were observed in the PB group. These effects were blunted by simultaneous stress exposure. Immunochemistry was used to stain for Bax and Bcl-2 (apoptosis markers). There was a four-fold increase in Bax/Bcl-2 ratio in the heart of PB and PB+Stress treated mice while an attenuation was observed in aortic endothelium. Results suggest that a relatively short-term continuous PB exposure may have adverse effects on the heart and blood vessels, independently of changes in MAP and HR.

Acetylcholinesterase↗

PubMed2005

Measurement of plasma catecholamines in small samples from mice.

INTRODUCTION: A method is described by which it is possible to obtain measurements of plasma catecholamines in small samples from resting chronically catheterized mice. METHODS: Standard alumina extraction procedures were systematically altered to maximize the recovery of catecholamines from 25-mul samples. The technique used commonly available HPLC with electrochemical detection (EC) equipment which was optimized according to the manufacturers' guidelines. RESULTS: The limit of detection is 40 pg/ml plasma noradrenaline and 20 pg/ml of plasma adrenaline and the resting levels were 300 pg/ml for noradrenaline and 80 pg/ml for adrenaline, both much lower than previously published. Comparison of resting levels from catheterized mice with those obtained by CO2 plus decapitation and rapid decapitation reveal increases comparable to those reported following immobilization stress. The catecholamines adrenaline and noradrenaline were differentially increased by the two euthanasia methods. DISCUSSION: The method was reliable, simple to perform and adequately sensitive. The resting levels of plasma catecholamines in mice are lower than previously published using a different sampling method. Differences in the norepinephine and adrenaline increases produced by the different methods of euthanasia suggest caution in the selection of method in studies of sympathetic function.

Animals↗

PubMed2005

Vascularity and pain in the patellar tendon of adult jumping athletes: a 5 month longitudinal study.

BACKGROUND: This study investigated changes in tendon vascularity in 102 (67 men and 35 women) volleyball players over a 6 month competitive season. METHODS: Athletes were examined with both grey scale ultrasound and standardised colour Doppler settings. Vessel length and pain were measured each month on five separate occasions. Vascular tendons were divided into (i) those that were vascular on all occasions (persistent vascularity) and (ii) those that were vascular on more than two but less than five occasions (intermittent vascularity). RESULTS: A total of 41 of the 133 abnormal tendons were vascular on two or more occasions. Of these, 16 had persistent vascularity and 25 had intermittent vascularity. There was no significant difference in the prevalence of vascularity between men and women. None of the tendons had a pattern of vascularity over the season that could be clearly interpreted as the onset or resolution of vascularity. Subjects with changes in both tendons were more likely to have persistent vascularity (p = 0.045). Vessels were longer in tendons with persistent vascularity (p<0.000) and pain was significantly greater (p = 0.043) than in tendons with intermittent vascularity. Tendons with intermittent vascularity had similar pain scores on all days, whether or not they had detectable blood flow. CONCLUSIONS: These data suggest that the presence of blood vessels is more likely to be the source of pain than the blood flow in them.

Adult↗

PubMed2004

Investigation of the role of SDHB inactivation in sporadic phaeochromocytoma and neuroblastoma.

Germline mutations in the succinate dehydrogenase (SDH) (mitochondrial respiratory chain complex II) subunit B gene, SDHB, cause susceptibility to head and neck paraganglioma and phaeochromocytoma. Previously, we did not identify somatic SDHB mutations in sporadic phaeochromocytoma, but SDHB maps to 1p36, a region of frequent loss of heterozygosity (LOH) in neuroblastoma as well. Hence, to evaluate SDHB as a candidate neuroblastoma tumour suppressor gene (TSG) we performed mutation analysis in 46 primary neuroblastomas by direct sequencing, but did not identify germline or somatic SDHB mutations. As TSGs such as RASSF1A are frequently inactivated by promoter region hypermethylation, we designed a methylation-sensitive PCR-based assay to detect SDHB promoter region methylation. In 21% of primary neuroblastomas and 32% of phaeochromocytomas (32%) methylated (and unmethylated) alleles were detected. Although promoter region methylation was also detected in two neuroblastoma cell lines, this was not associated with silencing of SDHB expression, and treatment with a demethylating agent (5-azacytidine) did not increase SDH activity. These findings suggest that although germline SDHB mutations are an important cause of phaeochromocytoma susceptibility, somatic inactivation of SDHB does not have a major role in sporadic neural crest tumours and SDHB is not the target of 1p36 allele loss in neuroblastoma and phaeochromocytoma.

Base Sequence↗

PubMed2004

Exercise training changes autonomic cardiovascular balance in mice.

Experiments were performed to investigate the influence of exercise training on cardiovascular function in mice. Heart rate, arterial pressure, baroreflex sensitivity, and autonomic control of heart rate were measured in conscious, unrestrained male C57/6J sedentary (n = 8) and trained mice (n = 8). The exercise training protocol used a treadmill (1 h/day; 5 days/wk for 4 wk). Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine, respectively. Autonomic control of heart rate and intrinsic heart rate were determined by use of methylatropine and propranolol. Resting bradycardia was observed in trained mice compared with sedentary animals [485 +/- 9 vs. 612 +/- 5 beats/min (bpm)], whereas mean arterial pressure was not different between the groups (106 +/- 2 vs. 108 +/- 3 mmHg). Baroreflex-mediated tachycardia was significantly enhanced in the trained group (6.97 +/- 0.97 vs. 1.6 +/- 0.21 bpm/mmHg, trained vs. sedentary), whereas baroreflex-mediated bradycardia was not altered by training. The tachycardia induced by methylatropine was significantly increased in trained animals (139 +/- 12 vs. 40 +/- 9 bpm, trained vs. sedentary), whereas the propranolol effect was significantly reduced in the trained group (49 +/- 11 vs. 97 +/- 11 bpm, trained vs. sedentary). Intrinsic heart rate was similar between groups. In conclusion, dynamic exercise training in mice induced a resting bradycardia and an improvement in baroreflex-mediated tachycardia. These changes are likely related to an increased vagal and decreased sympathetic tone, similar to the exercise response observed in humans.

Animals↗

PubMed2004

The corporo-glans ligament: description and functional significance of a ligament connecting the corpora cavernosa to the glans penis.

The two corpora cavernosa (CC) end blindly under cover of the glans penis (GP). The method of attachment of the CC to the GP could not be traced in the literature. The current communication investigated the hypothesis of a ligamentous attachment existing between the two corporal ends and the GP. In all, 18 male cadaveric specimens were studied by direct dissection and histologically. Six were neonates and 12 adults (mean age 32.3+/-10.6 s.d. y). After examining and photographing the connection between the CC and GP, sagittal, parasagittal, and coronal sections of the connection were stained and studied microscopically. A triangular fibrous tissue band connected the distal blind ends of the two CC with the GP. The base of this band was attached to the tunica albuginea of the two CC, while the apex was continuous with the fibrous septa between the sinusoids of the cavernous tissue of the GP. Microscopically, the ligament consisted of collagen and elastic fibers; in some sections, the collagen fibers of the tunica albuginea were continuous with those of the band. A band of collagen and elastic fibers could be identified connecting the two CC to the GP; we term it the 'corporo-glans ligament'. This ligament presumably affords the connection with rigidity, flexibility, and tissue strength. We suggest that it firmly connects the GP to the CC during penile thrusting. Further studies are required to assess the possible role of this ligament in erectile dysfunction.

Adolescent↗

PubMed2004

Predictors of children's body mass index: a longitudinal study of diet and growth in children aged 2-8 y.

OBJECTIVE: To identify longitudinal variables related to children's body mass index (BMI) (kg/m(2)) at age 8 y. DESIGN: A longitudinal design, with nine interviews per child from ages 2 to 8 y. SUBJECTS: In all, 70 white children (37 males, 33 females) who were continuous participants since infancy in the longitudinal study. Families were primarily middle and upper socioeconomic status. MEASUREMENTS: At each interview, children's height and weight were measured, and mothers provided 3 days of the child's intake data (a 24-h recall and 2 days of food records). ANALYSES: Analyses used were means+/-s.d., correlations, repeated measures analysis of variance, and forward stepwise regression. BMI at each interview was calculated and age of adiposity rebound was determined. RESULTS: Children's BMI at 8 y was negatively predicted by age of adiposity rebound and positively predicted by their BMI at 2 y. Additionally, each model included one longitudinal dietary variable; mean protein and fat intakes recorded between 2 and 8 y were positive predictors of BMI at 8 y; mean carbohydrate intake over the same time period was negatively related to BMI at 8 y. R(2) values indicated that these three-variable models predicted 41-43% of the variability in BMI among children. BMI of 23% of the children exceeded the 85th CDC percentile. CONCLUSIONS: The results of this study show that factors in early life are associated with children's BMI at age 8 y.

Body Height↗

PubMed2004

Just thinking about targets can aggravate neglect on cancellation tests.

While many studies investigate how the visual features of targets influence cancellation performance in neglect, few, if any, even consider that thought processes, such as the use of an algorithm to identify targets, might similarly aggravate neglect. This single-case study of a patient with chronic neglect compared cancellation performance after manipulating (1) ease of visual target identification, (2) the use of an algorithm to identify targets, and (3) the material-specific nature of target cancellation. Neglect severity was defined by the number and location of target omissions. While each manipulation had a differential impact on neglect severity, the novel and interesting finding occurred during the second condition, when a math algorithm was used to identify targets. In this condition, target omissions increased relative to other tests and target cancellations were confined to the right half of the page. This is the first report, to our knowledge, that neglect on cancellation tests can be aggravated by an internal thought process, a math algorithm, as opposed to external manipulations of visual stimuli and procedural characteristics of cancellation tests. An important characteristic of the algorithm used in this study is that it appeared to activate the intact left cerebral hemisphere.

Aged↗

PubMed2003

A collimated, high-speed outflow from the dying star V Hydrae.

Stars with masses in the range 1-8 solar masses (M(\circ)) live ordinary lives for approximately 10(9)-10(10) years, but die extraordinary deaths. First, during their death throes as asymptotic giant branch (AGB) stars they eject, over 10(4)-10(5) years, half or more of their mass in slowly expanding, spherical winds, and then, in a short (a few 100-1,000 years) and poorly understood phase, they are transformed into aspherical planetary nebula. Recent studies support the idea that high-speed, jet-like flows play a crucial role in this transformation. Evidence for such outflows is indirect, however; this phase is so short that few nearby stars are likely to be caught in the act. Here we report the discovery of a newly launched, high-speed jet-like outflow in the nearby AGB star, V Hydrae. We have detected both proper motions and ongoing evolution in the jet. These results support a model in which the jet is driven by an accretion disk around an unseen, compact companion. We also find a central, dense equatorial disk-like structure which may enable and/or enhance the formation of the accretion disk.

Journal Article↗

PubMed2003

Multiple sclerosis: a study of chemokine receptors and regulatory T cells in relation to MRI variables.

Magnetic resonance imaging (MRI) remains the most valuable tool for monitoring disease activity and progression in patients with multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system (CNS) with presumably autoimmune etiology. Chemokine receptors have been implicated in MS as key molecules directing inflammatory cells into the CNS. Regulatory (CD4+CD25+) T cells (Tr cells) are important in suppressing autoimmunity, and their absolute or functional deficit could be expected in MS. In the present study, venous blood was obtained from MS patients concurrent with MRI examination of the brain, and expression of chemokine receptors CCR1, CCR2, CCR5, CXCR3 and CXCR4 by CD4 T cells and monocytes, proportions of Tr cells, as well as expression of CD45RO, CD95, CTLA-4, HLA-DR and interleukin (IL)-10 by Tr cells and non-Tr (CD25-) CD4 T cells was analyzed by flow cytometry. Surface expression of CXCR3 by CD4 T cells was downregulated in the group of patients with high lesion load (LL) on T2-weighted images and gadolinium (Gd)-enhancing lesions on T1-weighted images, compared to the group with high LL and no Gd-enhancing lesions, and to the group with low LL, suggesting internalization of CXCR3 due to the release of its chemokine ligand (IP-10/CXCL10) from active MS lesions. Proportions of Tr cells amongst all CD4 T cells, and expression of IL-10 by Tr cells were increased in the patients with high LL and Gd-enhancing lesions. These results suggest that there is correlation between MRI parameters, chemokine receptor expression and the status of circulating Tr cells in MS, but further studies need to discriminate between pathogenetically relevant and bystander phenomena.

Adult↗

PubMed2003

Development of a rapid and sensitive method for the quantitation of amphetamines in human plasma and oral fluid by LC-MS-MS.

Target analysis of amphetamines in biological samples is of great importance for clinical and forensic toxicologists alike. At present, most laboratories analyze such samples by gas chromatography-mass spectrometry. However, this procedure is labor-intensive and time-consuming, particularly as a preliminary extraction and derivatization are usually unavoidable. Here we describe the development of an alternative method. Amphetamines were isolated from human plasma and oral fluid using a simple methanol precipitation step and subsequently analyzed using reversed-phase liquid chromatography-tandem mass spectrometry. Quantitation of the drugs was performed using multiple reaction monitoring. The developed method, which requires only 50 microL of biological sample, has a total analysis time of less than 20 min (including sample preparation) and enables the simultaneous quantitation of 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, amphetamine, methamphetamine, and ephedrine in a single chromatographic run. Limits of detection of 2 microg/L or better were obtained. The method has been validated and subsequently applied to the analysis of plasma and oral fluid samples collected from current drug users.

3,4-Methylenedioxyamphetamine↗

PubMed2003

Development of a rapid and sensitive method for the quantitation of benzodiazepines in Calliphora vicina larvae and puparia by LC-MS-MS.

Liquid chromatography-tandem mass spectrometry (LC-MS-MS) is emerging as the tool of choice for rapid analysis and the detection of biologically active compounds in complex mixtures. We describe the development of a sensitive method for the simultaneous quantitation of 10 benzodiazepines in Calliphora vicina (Diptera: Calliphoridae) larvae and puparia. The use of larvae for toxicological analyses offers some technical advantages over putrefied tissue. Four sample pretreatment methods for isolating the benzodiazepines out of larvae were evaluated. A simple homogenization, followed by acetonitrile precipitation yielded the highest recoveries. Puparia were pulverized and extracted by ultrasonification in methanol. All extracts were subsequently analyzed using reversed-phase LC-MS-MS. Larvae and puparia calibrators containing benzodiazepines at concentrations ranging from 25 to 750 pg/mg and 50 to 500 pg/mg, respectively, were prepared and analyzed. The method was demonstrated to be linear over the ranges investigated. Limits of detection were from 1.88 to 5.13 pg/mg larva and from 6.28 to 19.03 pg/mg puparium. The developed method was applied to the determination of nordiazepam and its metabolite oxazepam in larvae and puparia of the Calliphora vicina fly that had been reared on artificial foodstuff (beef heart) spiked with 1 microg/g nordiazepam. The larvae were harvested at day 5 for analysis of drug content. The method was sufficiently sensitive to allow the detection of nordiazepam and oxazepam in a single larva or puparium.

Animals↗