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Biomedical subjects

M Morris

Publications and source records attributed to M Morris.

At least 37 records · Page 2Linked to original sources
PubMed2002

Effects of angiotensin II microinjected into medial amygdala on male sexual behavior in rats.

Research was undertaken to study the role of central angiotensin in the modulation of male sexual behavior, testing the effect of angiotensin II (Ang II) injections into the medial amygdaloid nucleus (MeA). The sexual behavior of adult male Wistar rats was evaluated, 15 min after bilateral intra-amygdaloid microinjection (0.3 microl) of saline and 5 doses of Ang II: 10; 25; 50; 100, and 150 fmol. The effects of the Ang II receptor blockade were also studied. We tested the effect of coinjection of Ang II (50 fmol) with the AT1 antagonist, losartan (20 pmol) and the AT2 antagonist, CGP 42112 (1 pmol). Ang II inhibited sexual behavior and this inhibition was prevented by the coinjection of AT1 antagonist, losartan, or the AT2 antagonist, CGP 42112. Results show that Ang II has a powerful effect on male sexual behavior, which may be mediated by both AT1 and AT2 receptors.

Amygdala↗
PubMed2001

Oxytocin and autistic disorder: alterations in peptide forms.

BACKGROUND: Oxytocin (OT) is synthesized as a prohormone that is sequentially processed to peptides. These peptides are the bioactive amidated form (OT) and the C-terminal extended peptides, OT-Gly, OT-Gly-Lys and OT-Gly-Lys-Arg, which are designated together as OT-X. As an extension of our previous study finding decreased plasma OT in autism, studies were conducted to determine whether there were changes in OT peptide forms in autistic children. METHODS: Twenty eight male subjects (97 +/- 20 months; range, 70-139 months), diagnosed with DSM-IV autistic disorder through observation and semi-structured interview, were compared with 31 age-matched nonpsychiatric control subjects (106 +/- 22 months; range, 74-140 months). Using OT antisera with different specificity for the peptide forms, we measured plasma OT and OT-X in each group. RESULTS: T tests showed that there was a decrease in plasma OT (t = 4.4, p <.0001), an increase in OT-X (t = 2.3, p <.03) and an increase in the ratio of OT-X/OT (t = 4.5, p <.0001) in the autistic sample, compared with control subjects. CONCLUSIONS: The results suggest that children with autistic disorder show alterations in the endocrine OT system. Deficits in OT peptide processing in children with autism may be important in the development of this syndrome.

Adolescent↗
PubMed2001

Rapid X-ray flaring from the direction of the supermassive black hole at the Galactic Centre.

The nuclei of most galaxies are now believed to harbour supermassive black holes. The motions of stars in the central few light years of our Milky Way Galaxy indicate the presence of a dark object with a mass of about 2.6 x 106 solar masses (refs 2, 3). This object is spatially coincident with the compact radio source Sagittarius A* (Sgr A*) at the dynamical centre of the Galaxy, and the radio emission is thought to be powered by the gravitational potential energy released by matter as it accretes onto a supermassive black hole. Sgr A* is, however, much fainter than expected at all wavelengths, especially in X-rays, which has cast some doubt on this model. The first strong evidence for X-ray emission was found only recently. Here we report the discovery of rapid X-ray flaring from the direction of Sgr A*, which, together with the previously reported steady X-ray emission, provides compelling evidence that the emission is coming from the accretion of gas onto a supermassive black hole at the Galactic Centre.

Journal Article↗
PubMed2001

Number of older siblings of individuals diagnosed with schizophrenia.

One of the most consistent epidemiological findings in schizophrenia research is the small excess of late winter/early spring births. There is also evidence that schizophrenia is associated with urban birth and with later birth order. One interpretation of these three findings is that respiratory viral infections brought into the household by children in crowded areas could disrupt foetal brain development and predispose to schizophrenia in later life. To further explore this hypothesis, case register data were used to assess if schizophrenics with a greater number of older siblings are more likely to be born in urban areas and during late winter/early spring months. Data from the Dublin and Three County Case Register were compiled relating to 2969 patients with schizophrenia and 5904 patients with neurosis. We used logistic regression analysis to determine if the number of older siblings differentiated schizophrenia from neurosis after controlling for the effects of gender, urban/rural birth, season of birth and sibship size, and to examine whether any interactions existed. The number of older siblings did not predict a diagnosis of schizophrenia over neurosis. There was no interaction between number of older siblings and urban birth, between number of older siblings and spring birth, or between number of older siblings, season of birth and urban birth. These data do not support the hypothesis that schizophrenia, by comparison with neurosis, is associated with an increased number of older siblings or that there is an interaction between number of older siblings, urban birth or season of birth.

Birth Order↗
PubMed2001

Enhanced salt intake in oxytocin deficient mice.

The maternal roles of oxytocin (OT) are well known, but recent work suggests that OT is also a vital component in fluid balance regulation. To explore the role of OT in salt/volume regulation, we studied NaCl intake in a genetically modified mouse strain lacking OT. Using male control and OT knockout mice (OTKO), we determined the circadian pattern of salt and water intake under need-free conditions. For the study of intake, a two-bottle choice system was used to provide access to water and 2% NaCl with computerized monitoring of licking activity. Salt licking activity (licks/24 h) for controls was 59 +/- 22 vs. 380 +/- 105 in OTKO (P < 0.05). The volume of salt consumed (ml/24 h) was 0.4 +/- 0.1 in controls vs. 1.8 +/- 0.4 in OTKO (P < 0.01). There was no statistical difference in the consumption of water between the groups. However, the initiation of water intake was shifted, with an advancement of almost 3 h in OTKO (P < 0.01). Differences in the timing of salt intake could not be determined due to the low volume of salt consumed by controls. Taken together, these data show that removal of OT amplifies the salt-seeking behavior associated with normal daily fluid fluctuations. The fact that OTKO voluntarily consume a normally aversive salt solution further implies that OT is a powerful regulator of circadian salt appetite.

Animals↗
PubMed2001

Quantitative in situ hybridization for peptide mRNAs in mouse brain.

The objective was to determine the feasibility of using a radioactive capture method (Fuji FLA 2000) and image analysis system for the measurement of peptide mRNA levels in specific brain regions in mice. As a test mRNA, we chose vasopressin (VP) and oxytocin (OT) because they are expressed in abundance in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). A comparison was made between free-floating and slide-mounted sections to determine which method yielded better results. Mouse brains were fixed in 4% paraformaldehyde (PFA) and processed for in situ hybridization using 35S-oligonucleotide probes for VP and OT. After overnight hybridization and high stringency washes, 25-microm brain sections and 14C standards were exposed to a BAS-IIIs Fuji imaging film over a range of times (4 h-6 days). Results showed that there was an intense hybridization reaction in the PVN and SON, making it possible to distinguish the specific brain regions. Using Image Gauge Software, the signal was quantified in PVN and SON. A comparison of the different exposure times showed that the signal could be measured after as little as 4 h. The intensity readings increased over time while the calculated radioactivity remained constant. The free-floating method was superior to the slide-based system, providing a lower background and a higher signal. The data illustrates the applicability of the phosphor imaging system for the reproducible measurement of mRNA levels in discrete regions of the mouse brain.

Animals↗
PubMed2001

Follow-up of patients with unexplained syncope and inducible ventricular tachyarrhythmias: analysis of the AVID registry and an AVID substudy. Antiarrhythmics Versus Implantable Defibrillators.

INTRODUCTION: A prospective registry and substudy were conducted in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study to clarify the prognosis and recurrent event rate, risk factors, and impact of implantable cardioverter defibrillator (ICD) therapy in patients with unexplained syncope, structural heart disease, and inducible ventricular tachyarrhythmias. METHODS AND RESULTS: Included in the AVID registry were patients from all participating sites who had "out of hospital syncope with structural heart disease and EP-inducible VT/VF with symptoms." In addition, 13 collaborating sites provided more in-depth clinical and electrophysiologic data as part of a formal prospective substudy. Patients in the substudy were followed by local investigators for recurrent arrhythmic events and mortality. Registry patients were tracked for fatal outcomes by the National Death Index. A total of 429 patients with syncope were entered in the AVID registry, of whom 80 participated in the substudy. Of the substudy patients, 21 patients (26%) had inducible polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF), 11 patients (14%) had sustained monomorphic VT <200 beats/min, and 48 patients (60%) had sustained monomorphic VT > or = 200 beats/min. The ICD was used as sole therapy in 75% of the syncope substudy patients (and with antiarrhythmic drug in an additional 9%) and in 59% of the syncope registry patients. Survival rates at 1 and 3 years were 93% and 74% for the substudy patients and 90% and 74% for the registry patients, respectively. Survival of the syncope substudy patients (predominantly treated by ICD) was similar to the VT patients treated by ICD and superior to the VT patients treated by an antiarrhythmic drug (P = 0.05) in the randomized main trial. Mortality events in the substudy were marginally predicted by ejection fraction (P = 0.06) but not by electrophysiologic study-induced arrhythmia. The significant predictor of increased mortality in the registry was age (P = 0.003) and of reduced mortality was treatment with ICD (P = 0.006). CONCLUSION: The results of these analyses support the role of the ICD as primary antiarrhythmic therapy in patients with unexplained syncope, structural heart disease, and inducible VT/VF at electrophysiologic study.

Anti-Arrhythmia Agents↗
PubMed2001

Providing information on complementary and alternative therapies and practitioners by producing a directory of practitioners.

This article describes the experience of the authors in producing a booklet to provide information on complementary and alternative therapies (CAM) in their local area. The practical steps needed to produce a booklet are described, including ways of involving local general practitioners, meeting with local therapists, recruiting contact persons for each therapy, designing and producing a booklet and launching the final version. The feedback from general practitioners and CAM practitioners is reported.

Complementary Therapies↗
PubMed2001

Evidence-based nursing Web sites: finding the best resources.

Evidence-based nursing is becoming an increasingly widespread phenomenon in the nursing profession. As the evidence-based nursing movement grows, the Internet/World Wide Web has become a vital information link for keeping pace with current science and medical advancements. This article describes Internet resources currently available to support evidence-based nursing practice, presents practical search methods for locating these resources, and suggests criteria for evaluating the "evidence" available on the Internet. Results of an Internet search for Web sites that met the proposed criteria for support of an evidence-based nursing practice located only three sites. The sites are described and evaluated for their usefulness. The authors demonstrate that although many Internet resources are available to nurses, few sites provide information or evidence supported by valid research.

Evidence-Based Medicine↗
PubMed2001

Basecalling with LifeTrace.

A pivotal step in electrophoresis sequencing is the conversion of the raw, continuous chromatogram data into the actual sequence of discrete nucleotides, a process referred to as basecalling. We describe a novel algorithm for basecalling implemented in the program LifeTrace. Like Phred, currently the most widely used basecalling software program, LifeTrace takes processed trace data as input. It was designed to be tolerant to variable peak spacing by means of an improved peak-detection algorithm that emphasizes local chromatogram information over global properties. LifeTrace is shown to generate high-quality basecalls and reliable quality scores. It proved particularly effective when applied to MegaBACE capillary sequencing machines. In a benchmark test of 8372 dye-primer MegaBACE chromatograms, LifeTrace generated 17% fewer substitution errors, 16% fewer insertion/deletion errors, and 2.4% more aligned bases to the finished sequence than did Phred. For two sets totaling 6624 dye-terminator chromatograms, the performance improvement was 15% fewer substitution errors, 10% fewer insertion/deletion errors, and 2.1% more aligned bases. The processing time required by LifeTrace is comparable to that of Phred. The predicted quality scores were in line with observed quality scores, permitting direct use for quality clipping and in silico single nucleotide polymorphism (SNP) detection. Furthermore, we introduce a new type of quality score associated with every basecall: the gap-quality. It estimates the probability of a deletion error between the current and the following basecall. This additional quality score improves detection of single basepair deletions when used for locating potential basecalling errors during the alignment. We also describe a new protocol for benchmarking that we believe better discerns basecaller performance differences than methods previously published.

Algorithms↗
PubMed2001

Enhanced central response to dehydration in mice lacking angiotensin AT(1a) receptors.

The objective was to determine the central nervous system (CNS) responses to dehydration (c-Fos and vasopressin mRNA) in mice lacking the ANG AT(1a) receptor [ANG AT(1a) knockout (KO)]. Control and AT(1a) KO mice were dehydrated for 24 or 48 h. Baseline plasma vasopressin (VP) was not different between the groups; however, the response to dehydration was attenuated in AT(1a) KO (24 +/- 11 vs. 10.6 +/- 2.7 pg/ml). Dehydration produced similar increases in plasma osmolality and depletion of posterior pituitary VP content. Neuronal activation was observed as increases in c-Fos protein and VP mRNA. The supraoptic responses were not different between groups. In the paraventricular nucleus (PVN), c-Fos-positive neurons (57.4 +/- 10.7 vs. 98.4 +/- 7.4 c-Fos cells/PVN, control vs. AT(1a) KO) and VP mRNA levels (1.0 +/- 0.1 vs. 1.4 +/- 0.1 microCi, control vs. AT(1a) KO) were increased with greater responses in AT(1a) KO. A comparison of 1- to 2-day water deprivation showed that plasma VP, brain c-Fos, and VP mRNA returned toward control on day 2, although plasma osmolality remained high. Data demonstrate that AT(1a) KO mice show a dichotomous response to dehydration, reduced for plasma VP and enhanced for PVN c-Fos protein and VP mRNA. The results illustrate the importance of ANG AT(1a) receptors in the regulation of osmotic and endocrine balance.

Animals↗
PubMed2001

Mice deficient in oxytocin manifest increased saline consumption following overnight fluid deprivation.

Male mice (9-13 mo of age) in which the gene for oxytocin (OT) had been deleted (OT -/-) were administered 0.5 M sodium chloride (NaCl) solution or tap water as a two-bottle choice test following overnight fluid deprivation (1600 to 1000 the following day). Compared with wild-type cohorts (OT +/+), OT-deficient mice ingested sevenfold greater amounts of saline in the first hour following reintroduction of fluids, P < 0.001, and fourfold greater amounts at the end of 6 h, P < 0.02. No significant difference in total water ingested was noted between the two genotypes at the end of either 1 or 6 h. If food deprivation accompanied the overnight fluid deprivation and food was reintroduced 1 h after the reintroduction of both water and saline, OT -/- mice still ingested greater amounts of saline, but not water, than OT +/+ mice at both 1 h, P < 0.001, and 6 h, P < 0.02. No differences were noted between genotypes in the daily intake of 0.5 M NaCl solution or water during a 3-day observation period before the overnight fluid deprivation. The volume of saline consumed in each 24-h observation period represented about one-tenth of the total fluids ingested in each genotype. We conclude that OT -/- mice display an enhanced salt appetite compared with OT +/+ mice when fluid deprived overnight. The salt appetite was only apparent in the presence of a perturbation such as fluid deprivation, which predisposes the animal to moderate hypovolemia. The observations support an inhibitory role for OT in the control of sodium appetite in mice.

Animals↗
PubMed2001

Differentiation of brain angiotensin type 1a and 1b receptor mRNAs: A specific effect of dehydration.

The objective was to examine the effect of dehydration on the expression of the angiotensin type 1 (AT(1)) receptor subtype mRNAs in mice by using an in situ hybridization method. The method used free-floating brain sections with (35)S-labeled probes specific for the untranslated 5' (AT(1a)) and 3' (AT(1b)) regions. AT(1a) and AT(1b) mRNA levels in the subfornical organ (SFO) and anterior third ventricle (AV3V) were quantified by using a phosphor-imaging system. Emulsion autoradiography with cresyl violet counterstaining was used to show cellular expression. Adult male C57BL mice (25 to 30 g) were given water ad libitum or were deprived of water for 48 hours. Dehydration produced increases in plasma osmolality (349+/-6 versus 314+/-4 mOsm/kg) and hematocrit (58+/-2% versus 47+/-1%). In situ hybridization showed that there was expression of AT(1a) and of AT(1b) mRNA in SFO and AV3V. Dehydration produced an increase in AT(1a) mRNA in both regions, with no changes noted for AT(1b). AT(1a) mRNA was increased in the AV3V region from 0.3+/-0.2 to 0.7+/-0.2 muCi/g and in the SFO from 0.6+/-0.3 to 1.0+/-0.2 muCi/g. These results provide information regarding the localization and physiological importance of a subset of angiotensin receptors that are important in volume and blood pressure regulation. AT(1a) and AT(1b) mRNAs showed a similar pattern of expression in rostral forebrain osmosensitive regions. However, osmotic/volume stimulation with dehydration produced specific activation of AT(1a) receptors. This verifies the role of AT(1a) receptors in volume regulation but raises a question concerning the physiological role of the AT(1b) subtype.

Animals↗
PubMed2001

Long-term evaluation of electrospray ionization mass spectrometric analysis of glycated hemoglobin.

BACKGROUND: Electrospray ionization mass spectrometry (ESIMS) has been successfully applied to the identification of hemoglobin (Hb) variants and the presence of glucose adducts (mass difference of 162 Da) on the separate Hb alpha and beta chains. To establish the potential of ESIMS as a routine and/or a reference method for the quantification of glycohemoglobin (HbA1c), we carried out a detailed evaluation over a 4-month period in a routine laboratory environment. METHODS: We optimized a procedure using ESIMS suitable for the routine quantitative analysis of HbA1c. We determined reliability and reproducibility over 4 months and assessed the potential for automated sample injection. We then compared values of 1022 blood samples from diabetic patients with a routine HPLC-based ion-exchange procedure (HA-8140; Menarini). RESULTS: Results of HbA1c measurement by ESIMS were available within 3 min. The analytical imprecision (CV) was 1.6-5.0% for both manual and automated injections. Data collection over the m/z 980-1400 range confirmed lower glycation of the alpha chain relative to the beta chain (0.66:1). Only one glycation was observed per globin chain. The overall glycohemoglobin (i.e., the average of alpha- and beta-chain glycations) measured by ESIMS (x) on 1022 blood samples was lower than by HPLC (y): y = 1.0432x + 0.4815. However, the ss-chain glycation measured by ESIMS was up to 20% higher than the value measured by ion-exchange HPLC and showed a close conformity, particularly at 5-10% HbA1c, with the ion-exchange Diabetes Control and Complications Trial (DCCT)-corrected and the United Kingdom National External Quality Assessment Scheme DCCT mean return values. CONCLUSIONS: ESIMS provides a precise measurement of HbA1c and, in particular, glycation of the beta chain. The method is robust and could be proposed as a procedure to substantiate HbA1c measurement and/or calibration.

Autoanalysis↗
PubMed2001

HER-2/neu (p185neu) protein expression in the natural or treated history of prostate cancer.

PURPOSE: Amplification of HER-2/neu gene and overexpression of its encoded product, the p185neu (HER-2/neu) tyrosine kinase membrane receptor, have been associated with tumor progression in certain neoplasms. We conducted this study to investigate patterns of HER-2/neu protein expression in prostate cancer, analyzing different points in the natural and treated history of the disease. EXPERIMENTAL DESIGN: Radical prostatectomy cases (83) and 20 metastatic lesions were studied for the association between HER-2/neu protein overexpression detected by immunohistochemistry and clinicopathological parameters, including time to prostate-specific antigen (PSA) relapse. RESULTS: HER-2/neu protein overexpression, defined as complete membrane staining in >10% of tumor cells using the Food and Drug Administration-approved Dako kit, was found in 9 of 45 (20%) of evaluable hormone naïve primary tumors and 23 of 34 (67%) primary tumors after androgen-deprivation therapy (P = 0.0001). Of the 20 metastatic lesions, positivity was noted in 16 (80%) of the cases. On univariate analysis, HER-2/neu overexpression was associated with pretreatment PSA (P = 0.011) and time to PSA relapse (P = 0.02). After controlling for pretreatment PSA, the association between hormone treatment and HER-2/neu was still observed. No association was found between HER-2/neu overexpression and Gleason score, capsular invasion, and tumor proliferative index determined by Ki67. CONCLUSIONS: These data suggest that there is significant HER-2/neu overexpression in primary tumors that persist after androgen deprivation. It also emphasizes the importance of characterizing tumors at determined points in the natural or treated history of prostate cancer when targeting treatment to specific biological processes.

Cohort Studies↗