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Biomedical subjects

J Porter

Publications and source records attributed to J Porter.

At least 19 recordsLinked to original sources
PubMed1995

Membrane hyperpolarisation by valinomycin and its limitations for bacterial viability assessment using rhodamine 123 and flow cytometry.

The ionophore, valinomycin, was investigated as a possible means of bacterial viability assessment using the fluorescent membrane potential dye rhodamine 123. Membrane hyperpolarisation in Escherichia coli, Pseudomonas fluorescens, Enterobacter aerogenes and Arthrobacter globiformis was examined during exponential growth and during stress by brief starvation in a high sodium, low potassium buffer using flow cytometric analysis of rhodamine 123 uptake. Dye uptake was variable both between species and amongst cells from the same culture. Exponential phase cells showed no increase in dye uptake due to valinomycin treatment. Stressed P. fluorescens cells responded to valinomycin treatment by increased dye uptake, while stressed E. coli and A. globiformis cells showed no response. Approximately 50% of stressed Eb. aerogenes cells responded to valinomycin. The results demonstrate the limitations of rhodamine dye for viability analysing the viability of diverse bacterial communities and underline the degree of cell heterogeneity in batch cultures.

Arthrobacter↗
PubMed1995

Evaluation of the suitability of bis-(1,3-dibutylbarbituric acid) trimethine oxonol, (diBA-C4(3)-), for the flow cytometric assessment of bacterial viability.

The usefulness of oxonol (bis-(1,3-dibutylbarbituric acid)trimethine oxonol) as a generally applicable indicator of bacterial viability was investigated using untreated and killed cultures of a variety of bacterial genera. Killing methods involved either heat or bactericidal antibiotics. For all strains tested, the fluorescent dye showed significantly more intense staining of killed than untreated cells. The sensitivity of Aeromonas salmonicida to gentamicin was assessed using oxonol. Although the bacterium was shown to be sensitive to the antibiotic, there was a delay between the time cells lost culturability, as judged by numbers of colony forming units, and that for which a dead cell population could be detected by flow cytometry.

Bacteria↗
PubMed1995

Gonadotropin-releasing hormone antagonists: novel members of the azaline B family.

A series of antagonists of gonadotropin-releasing hormone (GnRH) homologous to azaline B ([Ac-DNal1,DCpa2,DPal3,Aph5(Atz),DAph6+ ++(Atz),ILys8,DAla10]GnRH) was synthesized, characterized, and tested in a rat antiovulatory assay (AOA). Selected analogues were also tested in both an in vitro dispersed rat pituitary cell culture assay for inhibition of GnRH-stimulated luteinizing hormone release and an in vitro histamine release assay. The duration of action of some of the most potent and safest analogues in those assays was also determined in the castrated male rat in order to measure the extent (efficacy and duration of action) of inhibition of luteinizing hormone release. Structurally, this series of analogues has novel substitutions (X and Y) in the structure of the azaline B precursor: [Ac-DNal1,DCpa2,DPal3,-Aph5(X),DAph6(Y),++ +ILys8,DAla10]GnRH. These substitutions were designed to confer increased hydrophilicity as compared to that of azaline B (determined by relative retention times on a C18 reverse phase column using a triethylammonium phosphate buffer at pH 7.3) or to make them more easily accessible synthetically. Some bulky substituents were introduced in order to probe the spatial limitations of the receptor's cavity. These substitutions include acylated 4-aminophenylalanine at positions 5 and/or 6 (29 analogues), N alpha-methylated backbone substitutions (six analogues), N omega-isopropylaminophenylalanine at position 8, and hydrophilic amino acids at position 1. Out of 20 novel analogues tested for long duration of action in this series, only seven ([Ac-DNal1,DCpa2,DPal3,Aph5,DAph6,ILys8 ,DAla10]GnRH, [Ac-DNal1,DCpa2,DPal3,Aph5(For),DAph6(For) ,ILys8,DAla10]GnRH, [Ac-DNal1,DCpa2,DPal3,Aph5(Ac),DAph6(Ac),- ILys8,DAla10]GnRH (acyline), [Ac-DNal1,DCpa2,DPal3,Aph5(Pio),DAph6++ +(Pio),ILys8,DAla10]GnRH, [Ac-DNal1,DCpa2,DPal3,Aph5(Atz),DAph6++ +(Ac),ILys8,DAla10]GnRH, [Ac-DNalDCpa2,DPal3,Aph5(Atz-beta Ala),DAph6(Atz-beta Ala),ILys8, DAla10]GnRH, [Ac-DNal1,DCpa2,DPal3,Aph5(Atz-Gab), DAph6(Atz-Gab),ILys8,DAla10]GnRH) had relative potencies and/or duration of action comparable to those of azaline B. The others were one-half to one-tenth as effective as azaline B. N alpha-Methylated backbone substitutions at position 5 yielded analogues that were significantly more hydrophilic presumably because of the breakage of the NH alpha-Tyr5 to Arg8-CO hydrogen bond reported to stabilize a beta-turn encompassing residues 5-8 and which favored beta-sheet formation as shown earlier by Haviv et al. This substitution resulted, however, in an increased potency in the histamine release assay and in significantly shorter duration of action. Similarly, attempts at replacing isopropyllysine in position 8 by either isopropyl-4-aminophenylalanine or isopropyl-4-(aminomethyl)phenylalanine resulted in loss of potency in the AOA. Changes in chirality at position 1 or 10 resulted in analogues that were one-tenth and one-half as potent, respectively, as acyline.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1995

National Medical Association Surgical Section position paper on violence prevention. A resolution of trauma surgeons caring for victims of violence.

The epidemic of intentional injury continues to be a leading cause of premature death in America. The ravages of violence are particularly devastating within the minority community. With this position paper from the Surgical Section of the National Medical Association (the country's oldest and largest organization of minority physicians), a group of trauma surgeons and surgical intensivists resolve to focus on underused violence prevention opportunities and to extend their spheres of influence beyond the walls of their institutions and emphasize violence prevention activities.

Humans↗
PubMed1995

Rapid assessment of physiological status in Escherichia coli using fluorescent probes.

Rapid and direct viability assessment of Escherichia coli in filtered, sterile lake water was possible using multiparameter flow cytometry. Fluorescent dyes were used as probes for different cellular functions (membrane potential, membrane integrity and intracellular enzyme activity), which were correlated with the ability of the cells to respond to nutrient addition while in a stressed state. Measurement of several criteria circumvented limitations imposed by other methods, and provided extensive evidence for the validity of the methods for monitoring cell viability during adoption of a viable-but-non-culturable state in starved E. coli. Macromolecular staining was concomitantly used to monitor changes in cellular protein, RNA and DNA as additional indicators of physiological status during starvation/stress.

Escherichia coli↗
PubMed1995

Psychosocial and clinical burden of thalassaemia intermedia and its implications for prenatal diagnosis.

Twenty eight patients with thalassaemia intermedia and their parents were interviewed using specifically designed questionnaires to evaluate psychosocial burden. Hospital notes were analysed for clinical burden. A wide variation was found for both patients and parents, ranging from virtually unaffected to severely affected. Normal sexual function and setting up a family were mentioned by patients and parents as being particularly important for quality of life. Over half (58%) of the patients had problems with sexual maturation and functioning, and continuous monitoring of all patients with thalassaemia intermedia by a paediatric endocrinologist is therefore strongly indicated. Most parents said, in light of their experiences, that they would opt for prenatal diagnosis and termination of affected pregnancies even if a genotype predicting the mild form of disorder were discovered.

Abortion, Legal↗
PubMed1995

Haemochromatosis presenting as congestive cardiac failure.

A 24 year old man with congestive cardiac failure was found to have grossly increased transferrin saturations, raised serum ferritin, and an iron-laden myocardium on biopsy. Initial treatment with the iron chelator desferrioxamine was replaced by weekly venesection. He was placed on the cardiac transplant list because of severe left ventricular dysfunction but was later removed because his symptoms and function improved. He remains well with few symptoms and is maintained on regular venesection and testosterone injections.

Adult↗
PubMed1995

How have Zambian businesses reacted to the HIV epidemic?

OBJECTIVES: To evaluate the impact of HIV on businesses in Zambia and to assess attitudes towards HIV and HIV education in the workplace. METHODS: The personnel managers of 33 companies with a total workforce of 10,204 in Lusaka and in towns in the Copperbelt were visited by two members of the study team. The study was discussed and a questionnaire about the impact of HIV on their company was explained and left for completion from company records. RESULTS: All 33 questionnaires were returned. HIV was recognised to be a problem by 30 companies questioned. Seven said that it had affected recruitment and 11 production. 23 companies carried out pre-employment medicals. 17 companies demanded that some or all of their employees had an HIV test before employment. Nine companies were sure that a positive HIV test would prevent employment, 15 were unsure saying that there was no particular company policy. Two companies had recently changed their policy and had stopped discriminating against those with HIV. 12 companies had some HIV educational material available for their employees and five had someone (or an organisation that they used) to whom they could refer employees for HIV information and advice. Condoms were provided free to staff by five of the companies. All thought that HIV education in the workplace was an appropriate intervention. Mortality data showed a sevenfold increase in the crude mortality from 0.25-1.8 per 100 person-years from 1987-93, and an increasing trend in reported deaths from AIDS and HIV related conditions. CONCLUSIONS: HIV is having an important impact in the workplace in urban Zambia. Although many companies insist on pre-employment medicals, often including HIV testing, few have developed policies relating to test results. Some companies have instituted HIV education but there is a demand for this service to be available more widely. There has been a striking increase in mortalities in this working population, which seems likely to be related to HIV, although the cause of most deaths was not recorded.

AIDS Serodiagnosis↗
PubMed1994

Type 1 prophospholipase A2 propeptide in acute lung injury.

Neutrophil sequestration and activation in the pulmonary vasculature and interstitium are important in acute lung injury. Phospholipase A2 plays an important part in the production of potent inflammatory mediators in this syndrome. We used our ELISA for type 1 prophospholipase A2 activation peptides, which have the aminoacid sequence Asp-Ser-Gly-Ile-Ser-Pro-Arg (DSGISPR), to show that DSGISPR concentrations in plasma and urine are a sensitive and specific marker of acute lung injury in patients admitted to intensive care. The detection of DSGISPR in the plasma of 11 of 50 unselected patients had a sensitivity of 100% and a specificity of 93% for the presence or future development of acute lung injury.

Amino Acid Sequence↗
PubMed1994

The binding site on human immunoglobulin E for its high affinity receptor.

Immunoglobulin (Ig) E antibodies mediate allergic responses by binding to specific high affinity receptors, Fc epsilon RI, on mast cells and basophils. Previous studies have shown that the principal Fc epsilon RI binding site is located on the third constant domain, Fc epsilon 3, of IgE. Based on a model of the IgE Fc epsilon 3 (which is homologous to the second constant domain of IgG), homology scanning mutagenesis and replacement of individual residues were used to determine the specific amino acids of human IgE involved in binding to human Fc epsilon RI. The amino acids are localized in three loops, which form a putative ridge on the most exposed side of the Fc epsilon 3 domain of IgE and include Arg-408, Ser-411, Lys-415, Glu-452, Arg-465, and Met-469. The preponderance of charged residues suggests that IgE-Fc epsilon RI binding is mediated primarily by electrostatic interaction. Furthermore, it is possible to confer Fc epsilon RI binding to an IgG molecule by introducing these three IgE loops into the IgG C gamma 2 domain.

Amino Acid Sequence↗
PubMed1994

Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study.

OBJECTIVE: To evaluate the efficacy and safety of iloprost, a prostacyclin analog, administered intravenously in patients with Raynaud phenomenon secondary to systemic sclerosis. DESIGN: Multicenter, randomized, parallel placebo-controlled, double-blind study. SETTING: University medical centers. PATIENTS: 131 patients with systemic sclerosis (101 women, 30 men) ages 20 to 79 years. INTERVENTION: Patients were randomly assigned to receive one of two parallel treatments of five daily sequential, 6-hour intravenous infusions of iloprost (0.5 to 2.0 ng/kg per min) or to receive a similar volume of placebo. MEASUREMENTS: Frequency of Raynaud attacks, Raynaud severity score, physician's overall rating of treatment effect, and digital cutaneous lesion healing. RESULTS: Of the 131 patients enrolled, 126 completed the 5-day infusion and 114 (87%) completed at least 6 weeks of follow-up. Sixty-four patients were randomly assigned to receive iloprost and 67 patients, to receive placebo. The mean weekly number of Raynaud attacks decreased 39.1% with iloprost and 22.2% with placebo (P = 0.005). In addition, the mean percentage of improvement in a global Raynaud severity score during the entire 9-week follow-up was greater in patients given iloprost (34.8%) than in those receiving placebo (19.7%) (P = 0.011). The physician's overall rating of treatment effect showed greater improvement with iloprost than with placebo at week 6 (52.4% compared with 27.4%; P = 0.008) and week 9 (60.9% compared with 26.9%; P < 0.001). At week 3, 14.6% more patients receiving iloprost had 50% or more lesions heal compared with those given placebo (95% CI, 0.9% to 30%). During the infusion, 59 (92%) of the patients receiving iloprost had one or more side effects compared with 38 (57%) of the patients receiving placebo. CONCLUSION: Iloprost is effective for the short-term palliation of severe Raynaud phenomenon in patients with systemic sclerosis.

Adult↗
PubMed1994

Unexpected neurological deficits following recovery from anaesthesia.

Two cases of neurological dysfunction are presented. Neurological deficits after recovery from anaesthesia are unusual in young women perioperatively. In the first case, a 39-yr-old woman presented at 36-wk gestation with antepartum haemorrhage and in labour. Pregnancy had been complicated by pre-eclampsia and she underwent emergency Caesarean section under general anaesthesia without complication. The trachea was extubated when she was awake but almost immediately she became hypertensive, obtunded and reintubation was required. Her pupils became fixed and dilated but the Computerised Axial Tomogram (CT) was normal. A coagulopathy was evident. She made a full neurological recovery within 24 hr. On the same day, a previously healthy 41-yr-old woman who had undergone uneventful surgery for uterine prolapse 24 hr previously developed headache, nausea and over the next four hours signs of progressive brainstem ischaemia. The CT scan showed oedema of the mid- and hindbrain. Brainstem death was confirmed 12 hr later and the post-mortem revealed acute dissection of the vertebral artery secondary to cystic medial necrosis. Such dramatic neurological sequelae are rare but the importance of identifying "at risk" groups is underlined as is early recognition of neurological injury postoperatively.

Adult↗
PubMed1994

Central alpha-adrenergic involvement in morphine-mediated suppression of splenic natural killer activity.

Alpha 1-adrenergic pathways are involved in morphine-induced suppression of murine splenic NK activity. To investigate the level of involvement following morphine administration, the peripheral acting alpha-adrenoceptor antagonist doxazosin and the broad acting alpha-adrenoceptor antagonist phentolamine were employed. Mice preadministered phentolamine (2.0 mg/kg) exhibited a modest but insignificant suppression of splenic NK activity following morphine administration while mice preadministered doxazosin (1.0 mg/kg) or vehicle showed a significant decrease in splenic NK activity following morphine administration. Morphine was also found to significantly (P < 0.01) increase splenic serotonin levels (14.88 +/- 1.62 ng/mg) relative to saline-treated controls (7.3 +/- 0.9 ng/mg). Both phentolamine and doxazosin pretreatment completely or partially blocked morphine-mediated elevation of splenic serotonin levels, respectively. Morphine administration decreased the ability of NK cells to form conjugates with target (YAC-1 lymphoma) cells and decreased the number of active killer cells within the conjugate population. Collectively, these results implicate central alpha-adrenergic involvement following acute morphine administration in suppressing splenic NK activity indirectly through a reduction in the number of effector-target conjugates and active cytolytic effector cells.

Animals↗
PubMed1994

Frequency distribution of dapsone N-hydroxylase, a putative probe for P4503A4 activity, in a white population.

Phenotypic trait values in 166 healthy white subjects (age range, 18 to 88 years) were determined for dapsone N-hydroxylation, dapsone N-acetylation, debrisoquin 4-hydroxylation, and S-mephenytoin 4'-hydroxylation after single oral dose administration of the probe drugs dapsone (100 mg), debrisoquin (10 mg), and mephenytoin (100 mg). No associations or evidence of cosegregation were found between the individual routes of metabolism. Dapsone N-hydroxylation exhibited a unimodal distribution, with marked (tenfold) intersubject variability, and aging was associated with reduced N-oxidation. However, the other measured routes of metabolism were age independent, but intersubject variability in all of the trait measurements increased with age. In subjects younger than 50 years, S-mephenytoin 4'-hydroxylation was modestly (34%) less in men than in women. In contrast, dapsone N-acetylation, dapsone N-hydroxylation, and debrisoquin 4-hydroxylation were not influenced by gender. Previous smoking habit and alcohol consumption were not associated with a difference in any of the four routes of metabolism. Accordingly, the measured phenotypic traits of drug oxidation and N-acetylation appear to be quite robust in regard to some common demographic variabilities present in population studies, with the exception of dapsone N-hydroxylase, which is affected by aging.

Acetylation↗