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Biomedical subjects

A Morris

Publications and source records attributed to A Morris.

At least 73 records · Page 4Linked to original sources
PubMed2001

A numerical model for magnetic induction tomographic measurements in biological tissues.

A finite-difference model has been developed for simulating measurements in magnetic induction tomography (MIT) for biological tissues. The model has three stages: (1) computation of the distribution of current induced in a volume of dielectric due to the magnetic field from an excitation coil; both the electrical conductivity and permittivity of the dielectric are taken into account: (2) computation of the e.m.f. induced in the sensing coil directly from the excitation coil; (3) computation of the e.m.f. induced in a sensing coil due to the current distribution in the dielectric. From the results of stages (2) and (3), the change in signal in the sensing coil due to the dielectric can be obtained, in magnitude and phase, as a fraction of the signal received in the absence of the dielectric. The peak values in the modelled curves agreed to within 14% of practical measurements at 10 MHz on volumes of saline solution with conductivities in the range 0.7 to 6 S m(-1).

Computer Simulation↗
PubMed2001

Childhood asthma.

Explore the source record for details and available documents.

Adrenergic beta-Agonists↗
PubMed2001

Apoptosis in squamous cell carcinoma of the lung: correlation with survival and clinicopathological features.

AIMS: Apoptosis is recognised as a physiological mechanism for controlling cell numbers and its subversion is thought to contribute to carcinogenesis. The aims of this study were to measure the apoptotic index (AI) in a series of squamous cell carcinomas (SCCs) of the lung using standard histological staining and confirm this by immunohistology using an antibody to an apoptosis specific protein (ASP), and to seek to correlate the AI with clinicopathological parameters. METHODS: Sections of 134 SCCs were stained by haematoxylin and eosin (H&E) for counting apoptotic bodies of determine the AI (number of apoptotic bodies/10,000 tumour cells); 26 of these were also stained with anti-ASP antibody and the proportion of ASP positive cells counted. Clinical data were obtained from hospital notes. RESULTS: The mean AI obtained by H&E staining of all 134 SCCs was 30.3 (SD, 24.75). Anti-ASP staining allowed easy identification of apoptotic bodies, and generated a somewhat higher index (mean, 51.4; SD 39); this was not a result of the selection of tumours because the AI by H&E in the subset stained with anti-ASP was 31.1. Regression analysis showed that the correlation between the two values of AI was highly significant (Rs = 0.9760; p < 0.001), indicating that the two methods were both reliable measures of apoptosis but that the anti-ASP staining is the more sensitive method. The tumours were grouped into high AI (> 50) and low AI (< 50) and survival analysis was carried out. The mean survival of the high AI group was 109 weeks and of the low AI group 72 weeks (p = 0.036). CONCLUSIONS: Anti-ASP staining is a reliable, easy, and sensitive method for assessing apoptosis in tumour sections and confirms the validity of the AI obtained by H&E staining. AI is a guide to the behaviour of SCCs of the lung.

Adult↗
PubMed2001

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: clinical course and description of causal mutations in two patients.

Hereditary deficiency of mitochondrial HMG-CoA synthase (mHS, OMIM 600234) is a poorly defined, treatable, probably underdiagnosed condition that can cause episodes of severe hypoketotic hypoglycemia. We present clinical follow-up and molecular analysis of the two known mHS-deficient patients. The diagnosis of mHS deficiency is challenging because the symptoms and metabolite pattern are not specific. Moreover, enzyme analysis is technically difficult and requires sampling of an expressing organ such as liver. The patients, now aged 16 and 6 y, have normal development and have had no further decompensations since diagnosis. Patient 1 is homozygous for a phenylalanine-to-leucine substitution at codon 174 (F174L). Interestingly, although the F174 residue is conserved in vertebrate mHS and cytoplasmic HS isozymes, a Leu residue is predicted in the corresponding position of HS-like sequences from Caenorhabditis elegans, Arabidopsis thaliana, and Brassica juncea. Bacterial expression of human F174L-mHS produces a low level of mHS polypeptide with no detectable activity. Similarly, in purified cytoplasmic HS, which in contrast to purified human mHS is stable and can be studied in detail, the corresponding F-->L substitution causes a 10,000-fold decrease in V(max) and a 5-fold reduction in thermal stability. Patient 2 is a genetic compound of a premature termination mutation, R424X, and an as-yet uncharacterized mutant allele that is distinguishable by intragenic single nucleotide polymorphisms that we describe. Molecular studies of mHS are useful in patients with a suggestive clinical presentation.

Adolescent↗
PubMed2001

Dynamic performances of different seat designs for low to medium velocity rear impact.

There is good evidence that seat design and impact severities in terms of delta-V and acceleration plays a role in AIS 1 neck injury outcomes in the event of a rear impact. This study evaluates a number of current production seats to assess the AIS 1 neck injury protection potential at different impact severities. Five different seat designs were exposed to four different impact severities in a sled simulating a rear impact. The same delta-V produced with different peak accelerations generated very different dummy responses. Head restraint position influenced the angular and horizontal displacement of the head relative to torso and the time of head to head restraint contact. The lowest motion of the head relative to the torso was found in the two anti-whiplash seats tested. The results of the study can be used for the design of future vehicle seats and anti-whiplash systems.

Abbreviated Injury Scale↗
PubMed2000

Engagement of the OX-40 receptor in vivo enhances antitumor immunity.

The OX-40 receptor (OX-40R), a member of the TNFR family, is primarily expressed on activated CD4+ T lymphocytes. Engagement of the OX-40R, with either OX-40 ligand (OX-40L) or an Ab agonist, delivers a strong costimulatory signal to effector T cells. OX-40R+ T cells isolated from inflammatory lesions in the CNS of animals with experimental autoimmune encephalomyelitis are the cells that respond to autoantigen (myelin basic protein) in vivo. We identified OX-40R+ T cells within primary tumors and tumor-invaded lymph nodes of patients with cancer and hypothesized that they are the tumor-Ag-specific T cells. Therefore, we investigated whether engagement of the OX-40R in vivo during tumor priming would enhance a tumor-specific T cell response. Injection of OX-40L:Ig or anti-OX-40R in vivo during tumor priming resulted in a significant improvement in the percentage of tumor-free survivors (20-55%) in four different murine tumors derived from four separate tissues. This anti-OX-40R effect was dose dependent and accentuated tumor-specific T cell memory. The data suggest that engagement of the OX-40R in vivo augments tumor-specific priming by stimulating/expanding the natural repertoire of the host's tumor-specific CD4+ T cells. The identification of OX-40R+ T cells clustered around human tumor cells in vivo suggests that engagement of the OX-40R may be a practical approach for expanding tumor-reactive T cells and thereby a method to improve tumor immunotherapy in patients with cancer.

Adjuvants, Immunologic↗
PubMed2000

Sp1 binding is critical for promoter assembly and activation of the MCP-1 gene by tumor necrosis factor.

The monocyte chemoattractant protein-1 gene (MCP-1) is induced by the inflammatory cytokine tumor necrosis factor through the coordinate assembly of an NF-kappaB-dependent distal regulatory region and a proximal region that has been suggested to bind Sp1 as well as other factors. To provide a genetic correlation for Sp1 activity in this system, a cell line homozygous for a targeted truncation of the Sp1 gene was derived and examined. We found that the lack of Sp1 binding activity resulted in the inability of both the distal and proximal regions to assemble in vivo even though the binding of NF-kappaB to distal region DNA was unaffected in vitro. We also found that Sp1 and NF-kappaB were the minimal mammalian transcription factors required for efficient activity when transfected into Drosophila Schneider cells. Additionally, Sp3 was able to compensate for Sp1 in the Drosophila tissue cell system but not in the Sp1(-/-) cell line suggesting that Sp1 usage is site-specific and is likely to depend on the context of the binding site. Together, these data provide genetic and biochemical proof for Sp1 in regulating the MCP-1 gene.

3T3 Cells↗
PubMed2000

Bronchiectasis in Alaska Native children: causes and clinical courses.

Although bronchiectasis has become a rare condition in U.S. children, it is still commonly diagnosed in Alaska Native children in the Yukon Kuskokwim Delta. The prevalence of bronchiectasis has not decreased in persons born during the 1980s as compared with those born in the 1940s. We reviewed case histories of 46 children with bronchiectasis. We observed that recurrent pneumonia was the major preceding medical condition in 85% of patients. There was an association between the lobes affected by pneumonia and the lobes affected by bronchiectasis. Eight (17%) patients had surgical resection of involved lobes. We conclude that the continued high prevalence of bronchiectasis appears to be related to extremely high rates of infant and childhood pneumonia. Pediatr Pulmonol. 2000;29:182-187. Published 2000 Wiley-Liss, Inc.

Adolescent↗
PubMed2000

Sequence variation within the RPGR gene: evidence for a founder complex allele.

In our study of sequence variation within the RPGR gene associated with X-linked retinitis pigmentosa, we and others have observed a high rate of new mutation within this gene, as all reported mutations are unique or uncommon. In this article we report the identification in a single family of a complex allele of 7 sequence variants in linkage disequilibrium, of which four result in amino-acid alterations (Arg425Lys, DGlu, Thr533Met and Gly566Glu). This complex allele was initially found in a family with XLRP. However, further study revealed an estimated prevalence of 4.3% (15/344 chromosomes) with this complex allele in the European population indicating the non-pathogenic nature of this allele and, along with previously reported polymorphisms, further supporting a high level of human protein diversity for RPGR. This common complex allele may have been established in the population as a founder effect. Complete gene sequencing identified a potential pathogenic sequence variant in the family described (IVS6+5G>A). This study emphasises the need to create a more complete picture of the allelic variation within a gene, suggests cautious interpretation of a phenotypic association with variant sequences, and highlights the potential problems associated with interpreting genetic studies for diagnostic purposes.

Alleles↗
PubMed2000

Soret spectroscopic and molecular graphic analysis of human semi-beta-hemoglobin formation.

The interaction of heme-free alpha (alpha(o)) and heme-containing beta (beta(h)) chains of human hemoglobin has been monitored in 0.1 M potassium phosphate buffer, pH 7 or 8, at 5 degrees C. Soret zero and first-derivative spectra were consistent with a uniform association reaction. Stopped-flow investigations demonstrated association rates on the order of 10(7) M(-1) s(-1). This was 100-fold more rapid than the reported rate of combination of alpha(h) and beta(h) proteins. This encounter-like rate of semi-beta-hemoglobin (alpha(o)beta(h)) formation was increased by raising the pH from 7 to 8. pH change is known to affect the spatial arrangement of AB-GH helical entities. Molecular graphic analysis of modeled alpha(o) protein superimposed over native alpha(h) protein revealed an apo Mb-like structure with well-defined AB-GH segments. Repositioning of these core helical segments, resulting in increased conformational freedom of the alpha1beta1 interface, was apparently responsible for the enhanced association properties of the alpha(o) protein.

Hemoglobin A↗
PubMed2000

Warfarin therapy and cataract surgery.

PURPOSE: Cataract extraction in the warfarinized patient poses special considerations. Warfarin will increase the haemorrhagic risk but, more importantly, cessation or reduction in anticoagulation may well lead to serious thromboembolic phenomena. The purpose of this study was to assess the impact that warfarinization has on cataract extraction. METHODS: One thousand consecutive cataract extractions performed at Christchurch Hospital between 1996 and 1998 were reviewed. Twenty-eight patients (29 eyes) were on warfarin. Reasons for anticoagulation, modification to treatment regimen and postoperative outcome measures were available for 23 eyes or 79% of the study population. RESULTS: The preoperative international normalized ratio (INR) ranged from 1.00 to 2.40+/-0.37 with a mean of 1.52. No thromboembolic phenomena occurred and four minor perioperative haemorrhages were noted, none of which affected the final visual outcome. CONCLUSIONS: If warfarin is required to counteract serious thromboembolic tendencies, then it should not be ceased perioperatively. The small numbers of perioperative haemorrhages that did occur were not visually significant.

Anesthesia, Local↗
PubMed2000

Life-threatening status asthmaticus treated with inhaled nitric oxide.

Inhaled nitric oxide (NO) was administered to 5 consecutive children with life-threatening status asthmaticus who required mechanical ventilation and did not respond to maximal medical management. Four showed a >20% decrease in baseline PaCO(2) (median PaCO(2) = 154 mm Hg, range = 95 to 229 mm Hg) occurring rapidly after the administration of inhaled NO. Three children, in addition to the index case, received continuous inhaled NO therapy, ranging from 5.5 to 21.5 hours. Systemic hypotension was not observed, and the maximum methemoglobin level was 1.9%. Four children survived to hospital discharge. Although the precise mechanism of action is not known, it appears that inhaled NO merits further study and may represent a life-saving therapy in this select patient population.

Bronchodilator Agents↗
PubMed2000

Cholesterol granulomas of the lungs associated with microangiopathic hemolytic anemia and thrombocytopenia in pulmonary hypertension.

Cholesterol granulomas unrelated to endogenous lipoid pneumonia, pulmonary alveolar proteinosis, or cholesterol pneumonia are a rare finding during pneumectomy or autopsy. They have been occasionally reported in association with pulmonary hypertension. We report a case where these lesions were associated with long-standing pulmonary hypertension and microangiopathic hemolytic anemia and thrombocytopenia. Plexiform lesions were present in the pulmonary vasculature secondary to pulmonary hypertension, causing hemolysis and thrombocytopenia. We suggest that destruction of red blood cells and platelets could provide membrane lipids that are taken up by phagocytic cells, which promotes the formation of these cholesterol deposits.

Adult↗
PubMed2000

Blood flow distribution in sorbent beds: analysis of a new sorbent device for hemoperfusion.

A new polymer-based sorbent cartridge has been recently developed for enhancing middle molecule removal during hemodialysis. The cartridge (Betasorb, Renaltech, New York, USA) has been designed to be placed in series with the dialyzer in the blood circuit. It is therefore important to evaluate the distribution of flow into the blood compartment of the device in order to assess if the surface of the sorbent is utilized to the best. For this purpose, a special imaging technique was utilized. Cartridges were analyzed during a simulated in vitro circulation at 250 and 350 ml/min of blood flow and 25% and 40% hematocrit. Cartridges were placed in vertical position and a cross longitudinal section 1 cm thick was analyzed in sequence by a helical scanner. Dye was injected into the arterial inlet and the progressive distribution was evaluated by sequential densitometrical measures carried out automatically by the machine. The sequential images analyzed by the scanner demonstrated excellent distribution of the flow in the blood compartment with minimal difference between the central and the peripheral regions of the compartment. In particular the following flow velocity pattern could be observed under the different experimental conditions tested. We may conclude that the cartridge design is adequate and no channelling effects could be detected in the blood compartment. The flow distribution is slightly affected by changes in flow rate and hematocrit showing an optimal utilization of the available surface for molecule adsorption.

Adsorption↗