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Biomedical subjects

G Morris

Publications and source records attributed to G Morris.

At least 37 records · Page 2Linked to original sources
PubMed1998

Lymphocyte inhibitor of TRAIL (TNF-related apoptosis-inducing ligand): a new receptor protecting lymphocytes from the death ligand TRAIL.

Apoptosis can be triggered by the engagement of cell surface receptors by their ligands. A growing number of receptors belonging to the TNF receptor family have been identified that contain a conserved cytoplasmic death domain. These include Fas, TNF-R1, lymphocyte-associated receptor of death (LARD), DR4, and TNF-related apoptosis-inducing ligand receptor inducer of cell killing-2 (TRICK2). The latter two are receptors for the cytotoxic ligand TNF-related apoptosis-inducing ligand (TRAIL), and one of the paradoxes raised by the cloning of these molecules was why do most cells not die upon contact with the widely expressed TRAIL molecule? This is a particular problem for lymphocytes that express DR4 and TRICK2 and are in constant circulation through TRAIL-expressing tissues. We have cloned LIT (lymphocyte inhibitor of TRAIL), which lacks a death domain. LIT is expressed predominantly on PBL, where it can competitively inhibit TRAIL-induced apoptosis through DR4/TRICK2, and may function to modulate lymphocyte sensitivity to TRAIL.

Amino Acid Sequence↗
PubMed1998

Interstitial cells of Cajal mediate enteric inhibitory neurotransmission in the lower esophageal and pyloric sphincters.

BACKGROUND & AIMS: Previous studies have suggested that a specific class of interstitial cells of Cajal (ICC) act as mediators in nitrergic inhibitory neurotransmission. The aim of this investigation was to examine the role of intramuscular ICC (IC-IM) in neurotransmission in the murine lower esophageal (LES) and pyloric sphincters (PS). METHODS: Immunohistochemistry and electrophysiology were used to study the distribution and role of IC-IM. RESULTS: The LES and PS contain spindle-shaped IC-IM, which form close relationships with nitric oxide synthase-containing nerve fibers. The PS contains ICC within the myenteric plexus and c-Kit immunopositive cells along the submucosal surface of the circular muscle. IC-IM were absent in the LES and PS of c-kit (W/Wv) mutant mice. Using these mutants, we tested whether IC-IM mediate neural inputs in the LES and PS. Although the distribution of inhibitory nerves was normal in W/Wv animals, NO-dependent inhibitory neurotransmission was reduced. Hyperpolarizations to sodium nitroprusside were also attenuated in W/Wv animals. CONCLUSIONS: The data suggest that IC-IM play an important role in NO-dependent neurotransmission in the LES and PS. IC-IM may be the effectors that transduce NO signals into hyperpolarizing responses. Loss of IC-IM may interfere with relaxations and normal motility in these sphincters.

Animals↗
PubMed1998

The effect of different membranes on onlay bone graft success in the dog mandible.

OBJECTIVE: The aim of this study was to compare resorbable membranes, nonresorbable membranes, and no coverage with respect to onlay bone graft healing in a dog. EXPERIMENTAL DESIGN: Each of four dogs had six corticocancellous blocks of ramus bone placed bilaterally as onlay grafts to the inferior lateral aspect of the mandible. On each side, one graft was left uncovered, one was covered with a collagen membrane, and one was covered with an expanded polytetrafluoroethylene membrane. Volume determinations were made at the time of graft placement and when the animals were killed. RESULTS: There were no statistically significant differences in bone volume or histologic outcome among the three groups.

Animals↗
PubMed1998

Incidence of spikes and paroxysmal rhythmic events in overnight ambulatory computer-assisted EEGs of normal subjects: a multicenter study.

The incidences of spikes and paroxysmal rhythmic events (PREs) in 10-h overnight EEGs of normal adult volunteers (n=135) were studied at 11 sites with a computer-assisted ambulatory EEG monitoring system with automatic spike and PRE detection. Spikes were evident in the overnight EEG of 1 subject (0.7%), and PREs were apparent in the overnight EEG of the same subject (0.7%). The incidences of spikes of 24 other subjects with a history of migraine and/or a family history of epilepsy were 12.5 and 13.3%, respectively. The overnight EEGs of these subjects were significantly more likely to show spikes than the overnight EEGs of subjects without migraine or a family history of epilepsy.

Adolescent↗
PubMed1997

Crystal structures of the inactive D30N mutant of feline immunodeficiency virus protease complexed with a substrate and an inhibitor.

Crystal structures of complexes of a D30N mutant of feline immunodeficiency virus protease (FIV PR) complexed with a statine-based inhibitor (LP-149), as well as with a substrate based on a modification of this inhibitor (LP-149S), have been solved and refined at resolutions of 2.0 and 1.85 A, respectively. Both the inhibitor and the substrate are bound in the active site of the mutant protease in a similar mode, which also resembles the mode of binding of LP-149 to the native protease. The carbonyl oxygen of the scissile bond in the substrate is not hydrated and is located within the distance of a hydrogen bond to an amido nitrogen atom from one of the two asparagines in the active site of the enzyme. The nitrogen atom of the scissile bond is 3.25 A from the conserved water molecule (Wat301). A model of a tetrahedral intermediate bound to the active site of the native enzyme was built by considering the interactions observed in all three crystal structures of FIV PR. Molecular dynamics simulations of this model bound to native wild-type FIV PR were carried out, to investigate the final stages of the catalytic mechanism of aspartic proteases.

Asparagine↗
PubMed1997

Decreased C-MYC and BCL2 expression correlates with methylprednisolone-mediated inhibition of Raji lymphoma growth.

Methylprednisolone (MP) and related corticosteroids are a fundamental part of regimens used to treat lymphoma and leukemia. In many of these malignancies, oncogenic activation of C-MYC and BCL2 is seen. Abnormalities of the tumor suppressor p53, which exerts growth-suppressing and apoptosis-enhancing functions through the transcriptional regulation of downstream genes including CDKN1, GADD45, and BCL2, are also often found. The goal was to determine the modulation of expression of the oncogenes (C-MYC and BCL2), the p53 pathway described above, and the apoptosis marker TGF-beta 1 in the human Raji lymphoma following MP treatment. Raji xenografts were grown in nude mice and growth curves characterized by sequential measurement. Mice were treated daily for 8 days with MP. Tumors were harvested untreated, or at 1 or 8 days after cessation of MP treatment, and the RNA was extracted. RT-PCR was used to determine the level of mRNA expression of the genes. Tumor growth was greatly reduced in the MP-treated mice. Gene expression levels for C-MYC and BCL2 were reduced at 1 day following MP and approached control levels 8 days after MP treatment. Expression levels of p53, CDKN1, and GADD45 were moderately and coordinately decreased at 1 day after cessation of MP treatment and remained repressed a week later. TGF-beta 1 exhibited no change in expression levels. These results suggest that decreased expression of C-MYC and BCL2 may play a role in the molecular events that initiate and are responsible for the growth inhibition of Raji lymphoma xenografts by MP.

Animals↗
PubMed1997

Contribution of gastrointestinal transit and pouch characteristics in determining pouch function.

AIM: To determine the contributions of gastrointestinal transit and pouch characteristics to bowel frequency in patients with an ileoanal reservoir and no pouchitis. METHODS: Twenty one patients who had undergone restorative proctocolectomy, with ileostomy closure at least eight months previously, and who had no history of pouchitis were recruited. They were prospectively classified on the basis of their bowel frequency: 11 patients had good pouch function (bowel frequency less than six per day) and 10 had poor function (bowel frequency more than six per day). Gastrointestinal transit was studied using a dual isotope technique and anal and pouch physiological examination was performed on all patients. RESULTS: Lag phase, 25% and 50% gastric emptying, small bowel transit time, and 10% and 50% pouch filling times, all for solids and liquids, were not significantly different between patients with good and poor function. Anal manometry and pouch and anal electrical sensitivity were also similar in the two groups. The volume of air and water required to elicit an initial sensation and the urge to defaecate were similar in both groups, but the maximum tolerated volume to both air (525 v 245 ml, good v poor function, median values) and water (625 v 370 ml) infusion was significantly (both p < 0.02) lower in patients with poor function. CONCLUSION: Maximum tolerated volume in the pouch, which may reflect pouch size, sensitivity, compliance, or a combination of these is the major determinant of pouch function. Gastrointestinal transit does not seem to be an important determinant of function.

Adult↗
PubMed1997

Health economics of gastroesophageal reflux disease.

The present study provides an overview of the current state of health economics studies of gastroesophageal reflux disease (GERD). It indicates the strengths and weaknesses of individual studies, and the state of health economics analysis in general as they apply to GERD. Specifically, this study adopts a pharmacoeconomic perspective, which is a subsection of health economics analytical methods, to provide a comparative analysis of alternative courses of action based on cost and consequence. The pharmacoeconomic outlook is most effective when it considers a comprehensive societal perspective, with special consideration given to other relevant viewpoints, such as the payer, the primary provider and, most important, the patient. Pharmacoeconomics provides several specific analytical techniques for GERD-related health economics analysis. The Canadian Association of Gastroenterology consensus conference on GERD in 1996 thought that a cost effective analysis was the most appropriate technique to assess the pharmacoeconomics of GERD. Six previous studies on GERD health economics have been performed comparing omeprazole with H2 receptor antagonists. These studies vary in cost data collected and in analytical techniques. In general, the existing outcome measurements of these previous health economics studies are not ideal. Namely, they combine various GERD grades, use randomized controls, are endoscopically based, assess pharmaceutical therapy only and are short term. More appropriate health economic trials in GERD, which focus on GERD management strategies and therapeutic treatment of GERD, need to be designed and conducted. These economic assessments, however, should not replace detailed thinking, careful observation, good judgement and common sense.

Canada↗
PubMed1996

Gastrointestinal transit in patients with idiopathic megarectum.

PURPOSE: In patients with idiopathic megarectum, it is unknown whether abnormality is limited to the dilated large bowel or whether the upper gut is abnormal, as in the various forms of chronic intestinal pseudo-obstruction. This has important implications for treatment, especially surgery. METHODS: Ten patients (4 females; median age, 18 (range, 17-26) years) with idiopathic megarectum had contrast studies of the upper and lower gut, radioisotope (technetium-99m liquid and indium-111 solid phase) measurement of gastric, small-bowel, and colonic regional transit, and radiopaque marker colonic studies. RESULTS: All patients had a dilated large bowel. No patient had radiographic evidence of upper gut dilation. Four patients had normal and six patients had abnormally slow gastric emptying. Both the radioisotope scans and radiopaque marker studies showed abnormal colonic transit. Regions of delay corresponded with the region of dilated bowel. Symptoms of abdominal distention and bloating did not correspond to abnormalities of gastric emptying but rather with effectiveness of rectal evacuation. CONCLUSION: Patients with idiopathic megarectum have abnormal colonic transit, delay occurring predominantly in the dilated gut. Marker studies are less sensitive than isotope studies but provide adequate information for clinical purposes. Although motility abnormalities of the upper gut are common, symptoms correlate with large-bowel abnormalities.

Adolescent↗
PubMed1996

Histamine forming capacity (HFC) and its modulation by H3 receptor ligands in a model of bronchial hyper-responsiveness.

The histamine forming capacity (HFC) of acutely challenged airways from sensitised guinea pigs was investigated. After exposure to nebulised bovine serum albumin (BSA) or normal saline, animals were sacrificed, the pulmonary HFC determined and concurrent in vitro histamine log concentration response curves were constructed for parenchymal strips and tracheal muscle, the latter was field stimulated to record neurogenic responses. Exposure to BSA increased the HFC above controls for 24 hours (p < 0.001) and log concentration response curves for the parenchymal strips were shifted slightly to the left with an increased maximum response. This change appeared 3 hours after exposure and remained elevated at 24 hours. Similar changes did not occur with the trachea. Pre-treatment with thioperamide augmented (p < 0.02) HFC and this increase was inhibited by alpha-methylhistamine (p < 0.05). A possible relationship may exist between increased responsiveness of lower airways to exogenous histamine and a raised endogenous formation, regulated by the H3 receptor.

Animals↗
PubMed1996

Integrating public health information and surveillance systems.

The Centers for Disease Control and Prevention (CDC) recognizes sound public health information is the essential ingredient of all of its work and the key to effective public health decision making. A CDC/ATSDR committee reached a consensus that CDC needed to streamline and consolidate its public health surveillance and information systems into an integrated system. With integrated systems, a wide range of diverse individual information systems will continue to exist but these systems must be coordinated, interconnected, comparable, and easy to use. The "glue" that holds these systems together consists of (1) uniform data standards, (2) communications networks, and (3) policy-level agreements regarding data access, sharing, and reduction of data collection burdens. By putting the appropriate policy-making apparatus and resources in place, CDC believes the end result will be a streamlined process that meets the information needs of CDC and its partners with less confusion and frustration.

Humans↗
PubMed1996

Health services market testing--the experience of the community services review team in British Forces Germany.

During 1993-1995 the health services in British Forces Germany were subjected to a market testing process by which the primary, community and acute health services for the British Servicemen and women, their families and attached civilian staff, a population of 70,000, were put out to competitive tender with the then current provider, the Defence Medical Services, as one tenderer for the contract. This paper outlines the methodology developed by the Health Alliance Community Services Review team in formulating a successful bid. It is considered that the process outlined could be of value to those involved in future market tests, commissioning projects or performance improvement programmes.

Community Health Nursing↗
PubMed1996

Aspergillosis in immunocompromised paediatric patients: associations with building hygiene, design, and indoor air.

BACKGROUND: Nosocomial aspergillosis is a well known complication of immunosuppression in cancer patients and those undergoing transplantation and has usually been associated with major building construction or demolition. An observational study is reported of the hospital environment associated with an outbreak of aspergillosis in a paediatric oncology ward. METHODS: All cases of aspergillosis were identified from the hospital records and categorised as definite or probable according to the extent of supportive clinical and laboratory findings. All relevant aspects of building ventilation, air filtration, and aerosol generation considered relevant were examined and air samples for fungi were taken in triplicate at 25 sites using a slit sampler with appropriate culture media. RESULTS: Six cases of aspergillosis were identified over one year out of the 148 patients who attended the unit - the only part of the hospital where cases were found. Examination of the building services and function suggested that the cause or source was isolated to this paediatric oncology/haematology ward and may have been attributed to a defective disposal conduit door as well as the dispersal of a contaminated aerosol from the ward vacuum cleaner which had the highest measured concentrations of Aspergillus fumigatus in or around the building (65 colony forming units (cfu)/m3 compared with 0-6 cfu/m3 elsewhere). No further cases were identified in the two years after these hygiene arrangements were changed. CONCLUSIONS: The investigation of this outbreak of nosocomial aspergillosis identified several possible sources of fungally contaminated aerosol which could have been implicated as the cause. Their modification was followed by a reduction in the incidence of further cases. Each should be incorporated as an issue of importance in hospital building design and hygiene.

Air Pollution, Indoor↗
PubMed1996

Dosimetric evaluation of copper-64 in copper-67-2IT-BAT-Lym-1 for radioimmunotherapy.

UNLABELLED: Copper-67 (67Cu) is an attractive radionuclide for radioimmuno-therapy because of its favorable physical and biologic characteristics. Current supplies of 67Cu, however, contain as much as 60% of 64Cu at the time of delivery. Scatter photons from 64Cu enter the 67Cu energy window, affecting image resolution and counting accuracy. The radiation dose to tissue is also altered. METHODS: A line source and a small vial source of 67Cu containing varying amounts of 64Cu were used to evaluate the impact of 64Cu on image resolution and activity quantitation, respectively. Identical pharmacokinetics for 67Cu and 64Cu was assumed, and the radiation dosimetry of 64Cu was assessed using quantitative imaging data for 67Cu because the amount of 64Cu could be calculated for any time after 67Cu production. MIRD formalism was used to estimate the therapeutic index, defined as the ratio of radiation dose to tumor divided by the radiation dose to bone marrow. RESULTS: As the amount of 64Cu increased, the full width at tenth maximum of the line spread function increased, although there was no significant change in full width at half maximum. The number of scatter counts from 64Cu increased as the amount of 64Cu or the size of the source region of interest increased. When 64Cu was 25% of the total activity, less than 10% of the total 67Cu photopeak counts detected with a scintillation camera were attributable to 64Cu. Although the tumor radiation dose per unit of activity (cGy/GBq) from 67Cu was five times greater than that from 64Cu, the marrow dose (CGy/GBq) from 67Cu was only three times greater than that from 64Cu. Therefore, the therapeutic index was diminished by the presence of 64Cu. When 64Cu radioimpurity was less than 25% of the total activity, there was less than a 10% decrease in the therapeutic index. CONCLUSION: The shorter physical half-life of 64Cu relative to that of 67Cu and slower uptake and longer retention of antibody by tumor than by marrow result in a lower therapeutic index for 64Cu. The 25% radioimpurity of 64Cu causes less than 10% deviation in activity quantitation and diminution in the therapeutic index. The change in therapeutic index is predictable over time and can be used to determine the optimal time for radiopharmaceutical administration.

Bone Marrow↗
PubMed1996

Pseudohypoaldosteronism with normal blood pressure.

In adults, persistent hyperkalemic distal renal tubular acidosis in the absence of impaired renal function is an unusual abnormality usually associated with the syndromes of aldosterone deficiency or resistance. Herein, we present an adult with a clinical picture consisting of a normal blood pressure of 125/80 mmHg, normal blood volume, and glomerular filtration rate, with hyperkalemic distal renal tubular acidosis. The patent could spontaneously lower her urine pH to less than 5.5. Plasma renin activity was normal. Serum aldosterone level was appropriately elevated for the level of serum potassium. Following alkalinization of the urine, she was able to generate a urinary to blood PCO2 gradient [U-B PCO2] of 55 mmHg, and had a ten fold increased potassium secretion. After salt restriction and furosemide administration, her potassium secretion rate increased only twofold despite correction of he acidosis. The acidosis, as well as the hyperkalemia, was completely corrected after 9-alpha-Fluorohydrocortisone administration. Hydrochlorothiazide corrected the acidosis and hyperkalemia. Collectively, this picture suggests an underlying chloride shunt as the possible pathophysiological mechanism. Our case in unique in that it is not associated with hypertension.

Acidosis, Renal Tubular↗