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Biomedical subjects

R Morris

Publications and source records attributed to R Morris.

At least 109 records · Page 6Linked to original sources
PubMed1999

Automated protein model building combined with iterative structure refinement.

In protein crystallography, much time and effort are often required to trace an initial model from an interpretable electron density map and to refine it until it best agrees with the crystallographic data. Here, we present a method to build and refine a protein model automatically and without user intervention, starting from diffraction data extending to resolution higher than 2.3 A and reasonable estimates of crystallographic phases. The method is based on an iterative procedure that describes the electron density map as a set of unconnected atoms and then searches for protein-like patterns. Automatic pattern recognition (model building) combined with refinement, allows a structural model to be obtained reliably within a few CPU hours. We demonstrate the power of the method with examples of a few recently solved structures.

Adaptor Protein Complex alpha Subunits↗
PubMed1999

Architecture and connections of retrosplenial area 30 in the rhesus monkey (Macaca mulatta).

Because of the sharp curvature of the retrosplenial region around the splenium of the corpus callosum, standard coronal sections are not appropriate for architectonic analysis of its posteroventral part. In the present study, examination of the posteroventral retrosplenial region of the rhesus monkey in sections that were orthogonal to its axis of curvature (and therefore appropriate for architectonic analysis) has permitted definition of its architecture and precise extent. This analysis demonstrated that areas 29 and 30 of the retrosplenial cortex, as well as adjacent area 23 of the posterior cingulate cortex, extend together as an arch around the splenium of the corpus callosum and maintain their topographical relationship with one another throughout their entire course. Injections of anterograde and retrograde tracers confined to retrosplenial area 30 revealed that this area has reciprocal connections with adjacent areas 23, 19 and PGm, with the mid-dorsolateral part of the prefrontal cortex (areas 9, 9/46 and 46), with multimodal area TPO in the superior temporal sulcus, as well as the posterior parahippocampal cortex, the presubiculum and the entorhinal cortex. There are also bidirectional connections with the lateroposterior thalamic nucleus, as well as the laterodorsal and the anteroventral limbic thalamic nuclei. The connectivity of area 30 suggests that it may play a role in working memory processes subserved by the mid-dorsolateral frontal cortex in interaction with the hippocampal system.

Animals↗
PubMed1999

Meningococcal serogroup C conjugate vaccine is immunogenic in infancy and primes for memory.

The safety, immunogenicity, and immunologic priming of 2 dosages (2 microgram or 10 microgram) of a meningococcal C oligosaccharide-CRM197 conjugate vaccine was evaluated in 114 infants vaccinated at ages 2, 3, and 4 months. Antibody persistence and response to boosting with 10 microgram of meningococcal C polysaccharide were assessed. The meningococcal conjugate vaccine produced fewer local reactions than concurrent routine immunizations. Total serogroup C-specific immunoglobulin geometric mean concentration (GMC) increased from 0.3 microgram/mL before vaccination to 13.1 microgram/mL at age 5 months. Serum bactericidal antibody (SBA) geometric mean titers (GMTs) rose from <1:4 to 1:1057 at 5 months and fell by 14 months to 1:19. Following boosting, anti-C-specific immunoglobulin GMC rose to 15.9 microgram/mL and SBA GMT to 1:495. Antibody responses in the 10-microgram dose cohort were significantly higher at 5 months (P<.01) than in the 2-microgram dose cohort but were lower after polysaccharide boosting (P=.02). This meningococcal conjugate vaccine was well tolerated and immunogenic and induced immunologic memory in infants.

Bacterial Capsules↗
PubMed1999

Epidemiological features of pertussis in hospitalized patients in Canada, 1991-1997: report of the Immunization Monitoring Program--Active (IMPACT).

To assess the morbidity associated with the continued high levels of pertussis, we studied all children <2 years of age who were admitted to the 11 Immunization Monitoring Program--Active (IMPACT) centers, which constitute 85% of Canada's tertiary care pediatric beds. In the 7 years preceding implementation of acellular pertussis vaccine, a total of 1,082 pertussis cases were reported, of which 49.1% were culture-confirmed. The median age of the patients was 12.4 weeks; 78.9% of cases were in children <6 months of age. Complications of pertussis were common: pneumonia was reported in 9.4% of cases, new seizures in 2.3%, and encephalopathy in 0.5%. There were 10 deaths (0.9%), all in children < or =6 months of age. Duration of hospitalization was longer (9.3 days vs. 4.9 days; P = .001) and intensive care was required more frequently (19.2% vs. 4.9%; P = .001) in infants under <6 months of age than in those > or =6 months. Pertussis continues to cause significant morbidity and occasional mortality in Canada, particularly in young infants.

Canada↗
PubMed1999

Comparison of four methods for assessing airway sealing pressure with the laryngeal mask airway in adult patients.

We have compared four tests for assessing airway sealing pressure with the laryngeal mask airway (LMA) to test the hypothesis that airway sealing pressure and inter-observer reliability differ between tests. We studied 80 paralysed, anaesthetized adult patients. Four different airway sealing pressure tests were performed in random order on each patient by two observers blinded to each other's measurements: test 1 involved detection of an audible noise; test 2 was detection of end-tidal carbon dioxide in the oral cavity; test 3 was observation of the aneroid manometer dial as the pressure increased to note the airway pressure at which the dial reached stability; and test 4 was detection of an audible noise by neck auscultation. Mean airway sealing pressure ranged from 19.5 to 21.3 cm H2O and intra-class correlation coefficient was 0.95-0.99. Inter-observer reliability of all tests was classed as excellent. The manometric stability test had a higher mean airway sealing pressure (P < 0.0001) and better inter-observer reliability (P < 0.0001) compared with the three other tests. We conclude that for clinical purposes all four tests are excellent, but that the manometric stability test may be more appropriate for researchers comparing airway sealing pressures.

Adolescent↗
PubMed1999

Serum total homocysteine and coronary heart disease: prospective study in middle aged men.

OBJECTIVES: To examine the prospective relation between total homocysteine and major coronary heart disease events. DESIGN: A nested case-control study carried out within the British regional heart study, a prospective investigation of cardiovascular disease in men aged 40-59 years at entry. Serum total homocysteine concentrations were analysed retrospectively and blindly in baseline samples from 386 cases who had a myocardial infarct during 12.8 years of follow up and from 454 controls, frequency matched by age and town. RESULTS: Geometric mean serum total homocysteine was slightly higher in cases (14.2 micromol/l) than in controls (13.5 micromol/l), a proportional difference of 5.5% (95% confidence interval (CI) -0.02% to 10.8%, p = 0.06). Age adjusted risk of myocardial infarction increased weakly with log total homocysteine concentration; a 1 SD increase in log total homocysteine (equivalent to a 47% increase in total homo cysteine) was associated with an increase in odds of myocardial infarction of 1.15 (95% CI 1.00 to 1. 32; p = 0.05). The relation was particularly marked in the top fifth of the total homocysteine distribution (values >16.5 micromol/l), which had an odds ratio of 1.77 (95% CI 1.28 to 2.42) compared with lower levels. Adjustment for other risk factors had little effect on these findings. Total homocysteine concentrations more than 16.5 micromol/l accounted for 13% of the attributable risk of myocardial infarction in this study population. Serum total homocysteine among control subjects varied between towns and was correlated with town standardised mortality ratios for coronary heart disease (r = 0.43, p = 0.08). CONCLUSIONS: Serum total homocysteine is prospectively related to increased coronary risk and may also be related to geographical variation in coronary risk within Britain. These results strengthen the case for trials of total homocysteine reduction with folate.

Adult↗
PubMed1999

Inverse relation between Braak stage and cerebrovascular pathology in Alzheimer predominant dementia.

The most common neuropathological substrates of dementia are Alzheimer's disease, cerebrovascular disease, and dementia with Lewy bodies. A preliminary, retrospective postmortem analysis was performed of the relative burden of each pathology in 25 patients with predominantly Alzheimer's disease-type dementia. Log linear modelling was used to assess the relations between ApoE genotype, Alzheimer's disease, and cerebrovascular disease pathology scores. Sixteen of 18 cases (89%) with a Braak neuritic pathology score </=4 had, in addition, significant cerebrovascular disease, or dementia with Lewy bodies, or both. There was a significant inverse relation between cerebrovascular disease and Braak stage (p=0.015). The frequency of the ApoE-epsilon4 allele was 36.4%. No evidence was found for an association between possession of the ApoE-epsilon4 allele and any one pathological variable over another. In this series most brains from patients with dementia for which Alzheimer's disease is the predominant neuropathological substrate also harboured significant cerebrovascular disease or dementia with Lewy bodies. The data suggest that these diseases are perhaps pathogenetically distinct, yet conspire to produce the dementing phenotype.

Aged↗
PubMed1999

Discrimination, adjusted correlation, and equivalence of imprecise tests: application to glucose tolerance.

Comparison studies between physiological tests are often unsatisfactory for assessing their ability to distinguish between subjects. We recommend a simple but comprehensive protocol, using duplicate testing, that compares tests using 1) the discriminant ratio (DR) between the underlying between- and within-subject SDs, 2) correlation coefficients adjusted for attenuation due to test imprecision, and 3) unbiased estimation of the underlying linear relationship between test results. The following five alternative methods for assessing glucose tolerance were compared: fasting plasma glucose (FPG) as a single sample or as the mean of three 5-min samples (FPG3); the 1- and 2-h glucose during a low-dose intravenous glucose infusion (CIG); and the 2-h plasma glucose from a 75-g oral glucose tolerance test (OGTT). All tests had similar DRs ranging from 2.6 to 4.2. The adjusted correlation between FPG and CIG tests approached unity, and those between OGTT and other tests were approximately 0.9, showing that FPG3 provides similar information to the OGTT. FPG concentrations of 6.0 and 7.1 were found equivalent to the 1985 World Health Organization OGTT thresholds for impaired glucose tolerance and diabetes (7.8 and 11.1 mmol/l).

Administration, Oral↗
PubMed1999

Failure of exhalation during ventilation with the Dräger Oxylog 2000 ventilator.

We describe three cases in which there was failure of exhalation during mechanical ventilation with the Dräger Oxylog 2000 ventilator. Two potential mechanisms for this failure were identified, and were then experimentally reproduced on a test lung. First, a manufacturing fault in the silicone diaphragm in the ventilation valve was discovered. When a small hole in the diaphragm was incompletely perforated, a possible flap valve was formed, limiting exhalation. Second, failure of the one-way rubber disc valve to seat properly in its housing also prevented exhalation. These two previously unreported modes of ventilator failure have been identified. Careful checking of the ventilator circuit before each use is required.

Aged↗
PubMed1999

Functional MR imaging of confounded hypofrontality.

Comparatively reduced blood flow to frontal brain regions in patients with schizophrenia (hypofrontality) has been frequently observed in the last 25 years. However, there is an inconstant quality to hypofrontality, suggesting either confounded observation of a static (trait-like) abnormality, or that it is a genuinely dynamic (state-like) phenomenon. Possible confounds in functional magnetic resonance imaging (fMRI) studies of hypofrontality are classified. Methods for assessment and correction of stimulus correlated motion (an extracerebral confound) are reviewed in the context of fMRI data acquired from five schizophrenic patients and five comparison subjects during performance of a verbal fluency task. Factorial analysis of these and other data, acquired from the same subjects during a semantic decision task, is used to exclude a number of possible intracerebral confounds. By analogy to the historical controversy concerning the appearance of the planet Saturn viewed through early telescopes, understanding the inconstancy of hypofrontality in schizophrenia is likely to progress more by theoretically driven experiments that exploit the repeatability of fMRI than by further technological development alone.

Analysis of Variance↗
PubMed1998

First postpacing interval variability during right ventricular stimulation: a single algorithm for the differential diagnosis of regular tachycardias.

BACKGROUND: Failure to differentiate supraventricular from ventricular arrhythmias is the most frequent cause of inappropriate implantable cardioverter-defibrillator therapies. Although a sudden-onset criterion is available to differentiate sustained monomorphic ventricular tachycardias (SMVTs) and sinus tachycardias (STs), SMVTs arising during ST and SMVTs gradually accelerating above the cutoff rate can remain undetected. Regular paroxysmal atrial tachycardias (ATs) also can be undetected by onset and stability algorithms. We hypothesized that the first postpacing interval (FPPI) variability after overdrive right ventricular pacing may differentiate SMVTs from STs and ATs. METHODS AND RESULTS: FPPI variability was measured in 23 SMVTs (cycle length [CL] 366+/-50 ms [VT group]), 27 supraventricular tachycardias, 15 episodes of induced or simulated ATs (CL 376+/-29 ms [AT group]), and 12 exercise-related STs (CL 381+/-24 [ST group]). Sequences of trains of 5, 10, and 15 beats were delivered with a CL 40 ms shorter than the tachycardia CL. An FPPI absolute mean difference between consecutive trains of 5 and 10 beats (deltaFPPI) < or =25 ms identified all VTs (mean difference 5+/-7 ms). In the AT group, the deltaFPPI was >25 ms in all sequences (mean difference 129+/-60 ms, P<0.01). In the ST group, the deltaFPPI was >50 ms in all STs (mean difference 118+/-47 ms, P<0.01). CONCLUSIONS: FPPI variability may differentiate SMVT from AT and ST. This criterion is potentially useful in implantable devices that use a single ventricular lead.

Algorithms↗
PubMed1998

The expression of receptor tyrosine phosphatases is responsive to sciatic nerve crush.

Given the importance of phosphotyrosine signaling in growth cone dynamics, we have examined the embryonic and adult expression of receptor-like protein tyrosine phosphatases in sensory neurons and studied their responsiveness to nerve lesions in young adult animals. The phosphatases LAR, PTPsigma, and PTPalpha are expressed in most neurons of E14 and E18 rat embryo dorsal root ganglia, while BEM-1 is expressed in a more restricted subset of these neurons. These phosphatases continue to be expressed in young adult animals, suggesting that they have roles in mature as well as in developing dorsal root ganglia neurons. After an experimental sciatic nerve crush, the expression of the phosphatase genes was significantly and differentially altered in these neurons. PTPsigma mRNA was increased by 50% after 3 days, while LAR and PTPalpha expression dropped by 50 and 20%, respectively. BEM-1 mRNA levels were unaltered. These data show that mRNA levels of specific tyrosine phosphatase genes are highly responsive to nerve damage and may be reset to a new and potentially optimal pattern of expression more conducive for nerve regeneration. We propose that tyrosine phosphatases are not only involved in primary axonogenesis but can also now be implicated in the molecular control of adult nerve repair.

Aging↗
PubMed1998

[Epidemiology of severe eye injuries. United States Eye Injury Registry (USEIR) and Hungarian Eye Injury Registry (HEIR)].

BACKGROUND: Both in industrialized and in developing nations, the devastating impact of ocular trauma on society is increasingly recognized. Lacking standardized surveillance systems, however, comparable epidemiological information has not been available previously. METHODS: For several years, the United States Eye Injury Registry (USEIR) and the Hungarian Eye Injury Registry (HEIR) have been collecting data on all types of serious ocular trauma, based on identical operating criteria and using standardized reporting forms. We performed a retrospective analysis comparing the two datasets, containing over 8,400 injuries from the U.S. and over 1,200 injuries from Hungary. RESULTS: Sixty percent of patients in the U.S. and 52% of patients in Hungary were less than 30 years of age, with an at least 80% male preponderance in both registries. The home was the most frequent place of injury in both countries (USEIR: 41%, HEIR: 35%); industrial premises represented no more than 14%. Guns were responsible for 12% of cases in the USEIR (HEIR, 1%). Champagne corks were identified as a unique and relatively common source of eye injury in Hungary (1.4%, as opposed to 0.07% in the U.S.). In the USEIR, 16% of injuries were caused by assault (HEIR, 24%; chi-square value = 36.7, p < 0.0000001). The enucleation rate was 12% in the U.S. and 1% in Hungary. CONCLUSIONS: The different findings in the two countries identify certain areas for the implementation of preventive measures (supplying champagne bottles with warning labels and a coordinated fight against violence in Hungary, stricter fireworks legislation in the U.S., public awareness for home injuries in both countries, etc.). Based on the encouraging results from this study, we plan to continue our efforts using modified reporting forms and an upgraded software. We invite additional countries to adopt the USEIR model.

Adolescent↗
PubMed1998

Subunit stoichiometry of a core conduction element in a cloned epithelial amiloride-sensitive Na+ channel.

The molecular composition of a core conduction element formed by the alpha-subunit of cloned epithelial Na+ channels (ENaC) was studied in planar lipid bilayers. Two pairs of in vitro translated proteins were employed in combinatorial experiments: 1) wild-type (WT) and an N-terminally truncated alphaDeltaN-rENaC that displays accelerated kinetics (tauo = 32 +/- 13 ms, tauc = 42 +/- 11 ms), as compared with the WT channel (tauc1 = 18 +/- 8 ms, tauc2 = 252 +/- 31 ms, and tauo = 157 +/- 43 ms); and 2) WT and an amiloride binding mutant, alphaDelta278-283-rENaC. The channels that formed in a alphaWT:alphaDeltaN mixture fell into two groups: one with tauo and tauc that corresponded to those exhibited by the alphaDeltaN-rENaC alone, and another with a double-exponentially distributed closed time and a single-exponentially distributed open time that corresponded to the alphaWT-rENaC alone. Five channel subtypes with distinct sensitivities to amiloride were found in a 1alphaWT:1alphaDelta278-283 protein mixture. Statistical analyses of the distributions of channel phenotypes observed for either set of the WT:mutant combinations suggest a tetrameric organization of alpha-subunits as a minimal model for the core conduction element in ENaCs.

Amiloride↗