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Biomedical subjects

J Morgan

Publications and source records attributed to J Morgan.

At least 55 records · Page 3Linked to original sources
PubMed2001

Mitochondria-based photodynamic anti-cancer therapy.

As photodynamic therapy (PDT) becomes established as a treatment for cancer, there is increasing interest in identifying critical mechanisms of cell killing and understanding the bases for effective photosensitizers. The existence of multiple cellular targets makes it difficult to distinguish the critical events leading to cell death from PDT. However, with more sensitive techniques to detect photosensitizer localization, the isolation of PDT-resistant and -sensitive mutants and the use of innovative molecular and biochemical strategies to map cellular events occurring during and after photosensitization, some order is emerging from the chaos. The subcellular localization of many photosensitizers and the early responses to light activation indicate that mitochondria play a major role in photodynamic cell death. PDT with many agents which damage or inhibit different or multiple mitochondrial targets has many of the desirable characteristics for an effective anti-cancer therapy.

Anticarcinogenic Agents↗
PubMed2001

CD55 is over-expressed in the tumour environment.

CD55 is a protein that protects cells from complement-mediated attack. 791Tgp72 is an antigen which has been used successfully as a target for both tumour imaging and cancer vaccines. 791Tgp72 has recently been identified as CD55. Quantitative expression of CD55 in the tumour environment was therefore studied. Tumour cells showed a 4-100-fold increase in CD55 cell surface expression when compared to normal cells. Immunohistochemical staining of colorectal tumours also revealed high expression of CD55 in the stroma. To examine the source of this stromal CD55 the ability of both epithelial cells and endothelial cells to produce extracellular CD55 was measured. Tumour cell lines deposit CD55 into their extracellular matrix (ECM) in direct proportion to their cell surface expression. In contrast the ECM from HUVEC cells contained large amounts of CD55 despite expressing low levels of CD55 on their cell surface. Furthermore expression of CD55 on HUVEC cells was increased by exposure to VEGF. Although it remains unclear why CD55 is upregulated in the tumour environment its high level of expression on tumour cells and associated endothelium may explain why it is a good target for both imaging and immunotherapy.

Antigens, Neoplasm↗
PubMed2001

Rapid and sensitive quantitation of antibiotics in fermentations by electrospray mass spectrometry.

Electrospray ionisation mass spectrometry (ESI-MS) has been used for the determination and quantitation of a broad range of 24 antibiotics, from groups including aminoglycosides, beta-lactams, tetracyclines, antifungals and glycopeptides. Spectra have been acquired for all 24 antibiotics derived from pure samples dissolved in acetonitrile/water, along with samples extracted from complex fermentation liquor. Quantitation was carried out by the detection of the protonated molecules, using time-scheduled single-ion monitoring (SIM). ESI-MS was used to detect and quantify to 5-microM levels. A one-step extraction of antibiotics with an organic solvent (methanol) was used for this rapid and simple procedure. Specificity is not matched by other methods and antibiotic analogues (e.g. the five forms of erythromycin) can be determined within minutes.

Anti-Bacterial Agents↗
PubMed2001

Acute and chronic physiological effects of silver exposure in three marine teleosts.

This study evaluated the physiological effects of waterborne silver (added as AgNO(3)) on seawater fish, using acute (48-72 h) high level exposures (250-650 microg/l Ag) on tidepool sculpins (Oligocottus maculosus), and chronic (up to 21 day) low level exposures (1.5-50 microg/l Ag) on tidepool sculpins, plainfin midshipmen (Porichthys notatus), and rainbow trout (Oncorhynchus mykiss). Sculpins were tested at different salinities. Acclimation to lower salinity (18 vs 30 ppt) led to altered physiology, with higher ammonia excretion (J(Amm)), lower oxygen consumption, and lower branchial and intestinal Na(+)/K(+)-ATPase activities, but no difference in drinking rate. Short-term exposure to high silver levels tended to stimulate M(O(2)), J(Amm), and drinking rate. However, long-term exposure to low levels of silver depressed both J(Amm) and M(O(2)), and also led to decreased drinking rates. Both inhibition and stimulation of Na(+)/K(+)-ATPase activity occurred, dependent upon length and concentration of exposure, salinity (18 vs 30 ppt), tissue (gill vs intestine), and fish species (sculpin vs midshipmen vs rainbow trout). While the effects were variable, due to differing balances between inhibitory and compensatory responses, chronic silver exposure significantly altered Na(+)/K(+)-ATPase activity levels in almost all tests. In total, these findings reinforce the view that intestinal osmoregulatory function (drinking, Na(+)/K(+)-ATPase activity) is an important site of toxic impact for waterborne silver, that gill Na(+)/K(+)-ATPase activity is also a site of impact, and that chronic exposures at silver concentrations (1.5, 14.5 microg/l Ag) close to current or proposed water quality guidelines (albeit much higher than normal environmental levels), exert a variety of sublethal effects on marine teleosts.

Ammonia↗
PubMed2001

Systematic review concerning the age of introduction of complementary foods to the healthy full-term infant.

OBJECTIVES: To evaluate existing data from published studies investigating outcomes (growth, nutritional status and morbidity) in relation to the age of introduction of complementary foods to the healthy full-term infant. To assess the methodological quality of current scientific evidence on which infant feeding recommendations are based. SEARCH STRATEGY: A database was created following a search of electronic databases MEDLINE and BIDS, a handsearch of relevant journals and consultation with international experts in infant feeding practices. The search was conducted during a 6-month period and encompassed the years 1982-1998. INCLUSION CRITERIA: Randomised/non-randomised controlled trials and cohort studies investigating the relationship to the health of full-term infants of the introduction of complementary foods to childhood health. DATA COLLECTION AND ANALYSIS: Assessment of studies for inclusion and their compliance with methodological criteria was undertaken independently by two reviewers and discrepancies were resolved by discussion. RESULTS: From over 400 published papers identified, 33 met specific inclusion criteria. Significant differences in baseline characteristics of subjects in included studies meant that data were not amenable to meta-analysis. The consensus of the authors was that, of the 33 included publications, 13 contained data supporting the current WHO recommendations which attempt to accommodate all infants, including those whose nutritional requirements are not met by exclusive breast-feeding for 6 months. An equal number contained data that would support a recommendation for delaying the introduction of complementary foods until 6 months of age within the study population. The remaining seven were unable to provide evidence to support a change from the current WHO infant feeding recommendations which state that 'infants should be fed exclusively on breast milk from birth to 4-6 months of age'. None of the studies met all the methodological criteria. CONCLUSIONS: This review has shown that there is a lack of clear evidence to either support or refute a change to the current recommendations for the age of introduction of complementary foods to the breast milk or formula fed infant. Whilst exclusive breast feeding for the first 6 months of life can support growth and development in some infants, sub-groups have been identified within certain populations who may require complementary feeding prior to this age.

Age Factors↗
PubMed2001

Assessment of pain by parents in young children following surgery.

BACKGROUND: We asked parents to assess pain in young children following surgery. METHODS: Assessments were carried out by both parents and an independent assessor using a behavioural observational scale. RESULTS: Forms were returned from the parents of 42 children aged 1-5 years. There were 123 joint assessments and there was a strong correlation between the scores by the observer and the parents (r2=0.84). Twenty-nine children experienced pain following discharge from hospital. CONCLUSION: Our findings suggest that parents can assess pain in young children following surgery. The management of pain following discharge from hospital can be improved.

Adult↗
PubMed2001

Leptospirosis mimicking acute cholecystitis among athletes participating in a triathlon.

Leptospirosis, a disease acquired by exposure to contaminated water, is characterized by fever accompanied by various symptoms, including abdominal pain. An acute febrile illness occurred in athletes who participated in an Illinois triathlon in which the swimming event took place in a freshwater lake. Of 876 athletes, 120 sought medical care and 22 were hospitalized. Two of the athletes had their gallbladders removed because of abdominal pain and clinical suspicion of acute cholecystitis. We applied an immunohistochemical test for leptospirosis to these gallbladders and demonstrated bacterial antigens staining (granular and filamentous patterns) around blood vessels of the serosa and muscle layer. Rare intact bacteria were seen in 1 case. These results show that leptospirosis can mimic the clinical symptoms of acute cholecystitis. If a cholecystectomy is performed in febrile patients with suspicious environmental or animal exposure, pathologic studies for leptospirosis on formalin-fixed, paraffin-embedded tissues may be of great value.

Acute Disease↗
PubMed2001

Generation and characterization of a defined mutant of Streptococcus suis lacking suilysin.

A defined allelic-replacement mutant of the sly gene, encoding a thiol-activated cytolysin, from a European isolate of Streptococcus suis serotype 2 was generated and characterized. Unlike the parental strain, it is nonhemolytic, noncytotoxic for cultured macrophage-like cells, avirulent in a mouse infection model, yet only slightly attenuated in a porcine model of systemic infection.

Animals↗
PubMed2001

An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia.

BACKGROUND: Omega-3 fatty acids, such as those present in fish oil, have been reported to prolong life in myocardial infarction survivors. These fatty acids can decrease serum triglyceride concentrations, but so far the doses used in trials examining their effects on coronary end points have had only minimal triglyceride lowering effects. OBJECTIVE: To examine the triglyceride lowering effectiveness, safety, and tolerability of Omacor, a concentrate of omega-3, long chain, polyunsaturated fatty acids from fish oil (84% of the total as opposed to an average of 35% in fish oil) over one year in patients with established coronary heart disease (CHD) and persisting hypertriglyceridaemia, despite receiving simvastatin in doses similar to those employed in the Scandinavian simvastatin survival study. SUBJECTS AND METHODS: 59 patients with CHD, receiving simvastatin 10-40 mg daily with serum triglycerides > 2.3 mmol/l, were randomised to receive Omacor 2 g twice a day or placebo for 24 weeks in a double blind trial. Forty six patients accepted the offer of active treatment for a further 24 weeks in an open phase of the trial. RESULTS: There was a sustained significant decrease in serum triglycerides by 20-30% (p < 0.005) and in very low density lipoprotein (VLDL) cholesterol by 30-40% (p < 0.005) in patients receiving active Omacor at three, six, and 12 months compared either to baseline or placebo. Omacor did not have any deleterious effect on low density or high density lipoprotein cholesterol or on biochemical and haematological safety tests. There was no adverse effect on glycaemic control in patients with diabetes, who showed a decrease in serum triglyceride, which was at least as great as in non-diabetic patients. One patient receiving placebo died of acute myocardial infarction. Three patients withdrew from the trial (two on placebo and one on active treatment). Omacor was generally well tolerated. CONCLUSION: Omacor was found to be a safe and effective means of lowering serum triglycerides over one year in patients with CHD and combined hyperlipidaemia, whose triglycerides remained elevated despite simvastatin treatment.

Adult↗
PubMed2001

A prospective study of the psychological impact on patients of first diagnosis of human papillomavirus.

This study assessed the psychological impact of the first time diagnosis of human papillomavirus (HPV) in consecutive clients attending the Hamilton Sexual Health Clinic, and sought to determine whether this changed over time. Clients with a diagnosis other than HPV and those found to have no diagnosis were compared with HPV clients. All participants completed a battery of questionnaires following their initial visit and again at 4 weeks. The battery consisted of the General Health Questionnaire, Illness Attitude Scales, the International Index of Erectile Function or the Brief Index of Sexual Function for Women, and a 6-question test of the client's knowledge of HPV. One hundred and one participants completed the first questionnaires and 47 of those completed follow-up questionnaires. We found those diagnosed with first episode of HPV had considerable psychological difficulties. However these were no different to those associated with other sexually transmitted infections (STIs) or even those with no active diagnosis.

Adolescent↗
PubMed2000

Outcome of case finding among relatives of patients with known heterozygous familial hypercholesterolaemia.

OBJECTIVES: To assess the feasibility of detecting new cases of heterozygous familial hypercholesterolaemia by using a nurse led genetic register. DESIGN: Case finding among relatives of patients with familial hypercholesterolaemia. SETTING: Two lipid clinics in central and south Manchester. SUBJECTS: 259 (137 men and 122 women) probands and 285 first degree relatives. RESULTS: Of the 200 first degree relatives tested, 121 (60%) had inherited familial hypercholesterolaemia. The newly diagnosed patients were younger than the probands and were generally detected before they had clinically overt atherosclerosis. Concentrations of serum cholesterol were, respectively, 8.4 (1.7 SD) mmol/l and 8.1 (1.9 SD) mmol/l in affected men and women and 5.6 (1.0 SD) mmol/l and 5.6 (1.1 SD) mmol/l in unaffected men and women. Screening for risk factors as recommended in recent guidelines for coronary heart disease prevention would have failed to identify most of the affected relatives in whom hypertension, diabetes mellitus, cigarette smoking, and obesity were uncommon. CONCLUSIONS: By performing cholesterol tests on 200 relatives, 121 new patients with familial hypercholesterolaemia were discovered. Because 1 in 500 people in the United Kingdom are affected by this condition, to detect a similar number by population screening over 60 000 tests would be required, and only a few of these patients would have been detected had cholesterol testing been restricted to those with other risk factors for coronary heart disease. A case exists for organising a genetic register approach, linking lipid clinics nationally.

Adolescent↗
PubMed2000

The American Red Cross disaster mental health services: development of a cooperative, single function, multidisciplinary service model.

Not until 1989 did the Red Cross officially recognize a need for a systematic and organized plan for the mental health needs of disaster survivors. Over the next decade, the Red Cross Disaster Mental Health Services program has developed and evolved to assist both disaster victims and the Red Cross workers who serve them to cope with the overwhelming stresses encountered by both groups in the aftermath of disasters. The Red Cross now coordinates a large and diverse group of mental health professionals from fields of psychology, psychiatry, nursing, social work, marriage and family therapy, and counseling who work together cooperatively. Cross-disciplinary conflicts are minimized by the Red Cross' generic approach to the various mental health professional specialties as functionally interchangeable in performing Red Cross duties. This article reviews the development of this process and describes one local Red Cross chapter's early experience as part of this effort.

Crisis Intervention↗
PubMed2000

Kinetic and ionic properties of the human HCN2 pacemaker channel.

Human cDNA coding for the hyperpolarization-activated "pacemaker" channel HCN2 was expressed in Phoenix cells and yielded an inward current (IhHCN2) activated on hyperpolarization. The average IhHCN2 was half-activated at -83.1 mV and its kinetics could be described by second-order Hodgkin-Huxley gating. The time constant curve was bell-shaped and peaked at -82.2 mV. With 115 mM external Na+ and 30 mM external K+, IhHCN2 reversed at -17.1 mV, and had a mean conductance of 5.6 nS. Reducing the external K+ or Na+ concentration led to a concentration-dependent reduction of the IhHCN2 conductance and to a hyperpolarizing shift of reversal potential. External Cs+ ions (5 mM) blocked IhHCN2 in a voltage-dependent way according to a Woodhull-type block model, at an electrical distance of 0.66 from the external membrane surface, and with a dissociation constant of 15 mM at 0 mV. Increasing cytoplasmic cAMP using forskolin increased IhHCN2 by shifting the current activation curve to more positive voltages (11.7 mV). Exposure of the intracellular side of inside-out macro-patches to cAMP led to a depolarizing shift of the channel open probability curve (15.2 mV with 10 microM cAMP). These results indicate that although hHCN2 channels share several properties with native cardiac f-channels, differences also exist in permeability and block properties, suggesting that native channels may not be composed simply of homomeric constructs.

Biological Clocks↗
PubMed2000

Corticotropin releasing hormone: therapeutic implications and medicinal chemistry developments.

Corticotropin releasing hormone (CRH, sometimes known as CRF) is an endogenous 41 amino acid peptide that has been implicated in the onset of pregnancy, the 'fight or flight' response, in addition to a large number of physiological disorders. Recently, medicinal chemists have developed a number of potent and selective compounds that show promise in a vast array of therapeutic uses. Herein we review the current status of research.

Amino Acid Sequence↗