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Biomedical subjects

A Griffin

Publications and source records attributed to A Griffin.

At least 37 records · Page 2Linked to original sources
PubMed1996

Non random usage of T cell receptor alpha gene expression in atopy using anchored PCR.

The T cell receptor (TCR) alpha beta heterodimer recognises antigenic peptide fragments presented by Class II MHC. This interaction initiates T cell activation and cytokine release with subsequent recruitment of inflammatory cells. Previous work from our group suggests a qualitative difference in variable alpha gene expression in atopy as compared to non atopic controls. In this study we examine TCR alpha repertoire using anchored PCR to provide a quantitative assessment of the V alpha and J alpha repertoire. One atopic (DRB1*0701,DRB1*15: DRB4*0101, DRB5*01: DQB1* 0303, DQB1*601/2) and one non-atopic (DRB1*0701,DRB1*03011/2: DRB4*01, DRB3*0x: DQB1* 0303, DQB1*0201/2) control were studied. Variable gene usage was markedly limited in the atopic individual. V alpha 1, 3, 8 accounted for 60% and J alpha 12, 31 30% of the gene usage. There was evidence of preferential V alpha-J alpha gene pairing and clonal expansion. We conclude that there is a marked non random TCR alpha gene distribution in atopy using both V alpha family and anchored PCR. This may be due in part to antigen driven clonal expansion.

Gene Expression↗
PubMed1996

Development of a measure of physical function for patients with bone and soft tissue sarcoma.

Patients undergoing limb salvage surgery for bone and soft tissue sarcoma of the extremities experience significant physical disability as a result of life-preserving treatment. The existing health status measures do not adequately evaluate physical function from the patient's perspective. This paper presents the developmental studies (item selection, reduction, reliability, validity and responsiveness) of a new measure, The Toronto Extremity Salvage Score (TESS). Patients with bone and soft tissue sarcoma (76 upper and 83 lower extremity) were randomly selected and mailed the TESS. Patients rated the severity and importance of physical disabilities; the response options included a 'not applicable' category and open-ended questions that allowed patients to suggest additional items for inclusion in the questionnaire. Therefore, patient perceptions were used to determine item content. Difficulty and importance frequencies were calculated and items rated 'totally unimportant' or 'not applicable' by 30% of the sample were eliminated. Extra items identified 30% of the time were added to the questionnaire. Internal consistency was evaluated by Cronbach's alpha. Test-retest reliability and validity were evaluated on subsequent patient samples. The intraclass correlation coefficient (ICC) was calculated for test-retest reliability and correlations with The Musculoskeletal Tumour Society Rating Scale (MSTS) were calculated for construct validity. Standardized effect sizes were calculated as a measure of responsiveness. Fifty upper extremity and sixty-six lower extremity patients responded to the mailed questionnaire. No items were eliminated based on importance or not applicable ratings. Sporting activities were identified as additional items in both the upper and lower extremity questionnaire. High internal consistency was demonstrated: 0.94 for the lower and 0.92 for the upper extremity questionnaires respectively. Test-retest reliability was evaluated at multiple time-points and the intraclass correlation coefficient was greater than 0.87 in all instances. Construct validity was shown by a moderate correlation with the MSTS. The effect sizes were large demonstrating responsiveness. The use of patients' perceptions in determining the content of the TESS has resulted in a reliable and valid measure that is able to detect change over time.

Activities of Daily Living↗
PubMed1996

Drug resistance and virologic response in NUCA 3001, a randomized trial of lamivudine (3TC) versus zidovudine (ZDV) versus ZDV plus 3TC in previously untreated patients.

OBJECTIVE: To study the effect of HIV-1 resistance to lamivudine (3TC) and zidovudine (ZDV), and syncytium-inducing (SI) phenotype on virologic response to treatment with ZDV, 3TC, or ZDV plus 3TC in previously untreated individuals with HIV-1 infection. DESIGN: A prospective virologic substudy of GlaxoWellcome protocol NUCA 3001. METHODS: HIV-1 isolates obtained at study entry and at week 12 were expanded in peripheral blood mononuclear cell (PBMC) culture, titered, and assayed for phenotypic and genotypic evidence of resistance to ZDV and 3TC, and for syncytium formation on MT-2 cells. RESULTS: Phenotypic and genotypic resistance to 3TC was detected in the majority of HIV-1 isolates from patients who received 3TC alone or in combination with ZDV. Despite showing 3TC resistance, subjects who received 3TC in combination with ZDV had significantly greater decreases in plasma HIV-1 RNA levels compared with those who received ZDV alone. Occurrence of the K7OR ZDV resistance mutation was significantly reduced in patients who received the 3TC/ZDV combination as compared with patients on ZDV monotherapy. Plasma HIV-1 RNA returned to near-baseline levels more quickly in patients with SI isolates at study entry. CONCLUSIONS: Despite the rapid emergence of 3TC resistance, combination therapy with 3TC plus ZDV resulted in greater reduction in plasma HIV-1 RNA levels over 24 weeks as compared to ZDV monotherapy. Prevention of ZDV resistance may contribute to the sustained activity of the combination therapy.

Adult↗
PubMed1996

Sharing antenatal care: client satisfaction and use of the 'patient-held record'.

Two hundred women (148 shared care patients and 52 clinic patients) completed a questionnaire about care received during pregnancy and the use of a patient-held record. Women receiving shared care reported higher levels of satisfaction with their care than clinic patients (p < 0.0001). Thirty-six percent of the women in shared care forgot to take their record to an appointment on at least 1 occasion. During the pregnancy, over half of the respondents in both groups made contact with the hospital for reasons other than for their regular visit. For both groups, convenience was the most frequently reported reason for choosing their model of care. Other important issues for shared care patients were that the service was more personal and more information was provided. Among clinic patients, safety and quality of care were identified as important. Problems involved with the patient holding the only complete pregnancy record are discussed.

Family Practice↗
PubMed1996

Electrophysiological and ultrastructural events evoked by methacholine and intracellular photolysis of caged compounds in cultured ovine trachea submucosal gland cells.

Cultured ovine trachea submucosal gland cells release lysozyme in response to extracellular application of secretagogues, including the muscarinic receptor agonist methacholine (20 microM). Investigation of the ultrastructure has shown that these cells contain electron-dense cored granules, which differ from the intact tissue, but appear to be released in response to the application of methacholine and can be arrested during exocytosis by the application of tannic acid. The release process appears to be linked to electrophysiological events activated by methacholine. Extracellular application of methacholine and intracellular photorelease of Ca2+ from DM-nitrophen evoked similar events suggesting that a rise in intracellular Ca2+ may occur following muscarinic receptor activation. Measurements of the reversal potential and the inhibitory action of the chloride channel blocker niflumic acid (10 microM) indicated that Ca(2+)-activated Cl- channel activity underlies these events. Some of the cultured submucosal gland cells also responded similarly to intracellular photorelease of inositol 1,4,5-trisphosphate, suggesting a possible link between muscarinic receptor occupation by agonist, release of calcium from stores, and activation of Ca(2+)-activated Cl- current. Secretion of lysozyme, methacholine-activated currents and currents evoked by intracellular photorelease of Ca2+ were also attenuated by the potent bronchodilator Ro 31-6930 (1 microM). We conclude that Ca(2+)-activated Cl- conductances play an important role in secretory processes in cultured submucosal gland cells. This may have a bearing on both physiological control of secretory events and regulation of the nature of airway surface liquid. Ca(2+)-activated Cl- channels may offer a potential target site for novel therapeutic agents.

Acetates↗
PubMed1996

Violence prevention program targeting Connecticut adolescents: description and preliminary results.

Recent statistics show that adolescents are increasingly becoming both the perpetrators and the victims of violent crime in our nation. At our institution, we have developed a violence prevention program specifically targeting adolescents. This three-hour workshop utilizes a multimedia style of presenting information that we believe is well suited to young audiences. To date, over 1,000 adolescents from all over the state have participated in our program. In addition to describing the program, we also summarize the results of program evaluations and demographic profiles completed by audience members. Most participants report that the program was successful in educating them about the causes and consequences of violent injury and offered them alternatives to violence in resolving difficult situations. It is our hope that the education we provide will translate into fewer violent injuries within the state of Connecticut.

Connecticut↗
PubMed1995

The effect of K+ channel openers on submucosal gland function and epithelial transport of the ferret trachea, in vitro.

The effects of three K+ channel openers on lysozyme output from submucosal gland serous cells and epithelial albumin transport following maintained submaximal stimulation by the secretagogues methacholine and phenylephrine were examined in the ferret trachea in vitro preparation. The K+ channel openers Ro 31-6930, 2-(6-cyano-2,2-dimethyl-2H-1-benzopyran-4-yl)-pyridine 1-oxide (10 nM-10 microM), levcromakalim, BRL38227 (10 nM-10 microM) and pinacidil (100 nM-10 microM) produced a concentration dependent inhibition of (20 microM) methacholine-induced lysozyme output, with pD2 values of 7.64, 7.72 and 7.28 respectively. Ro 31-6930 (10 nM-10 microM), levcromakalim (10 nM-10 microM) and pinacidil (1 nM-10 microM) also produced a concentration dependent inhibition of (100 microM) phenylephrine-induced lysozyme output, with pD2 values of 7.64, 6.55 and 9.16 respectively. Furthermore, glibenclamide (1 microM) produced a modest attenuation of the K+ channel opener effects on secretagogue-induced lysozyme output. All three K+ channel openers failed to produce any significant change in either methacholine or phenylephrine-induced albumin outputs. The K+ channel openers exerted marked effects on airway secretion processes, suggesting that these compounds may have an antisecretory effect. The relevance of the use of the K+ channel openers in airway disease remains to be determined.

Albumins↗
PubMed1995

Aspects of calcium-activated chloride currents: a neuronal perspective.

Ca(2+)-activated Cl- channels are expressed in a variety of cell types, including central and peripheral neurones. These channels are activated by a rise in intracellular Ca2+ close to the cell membrane. This can be evoked by cellular events such as Ca2+ entry through voltage- and ligandgated channels or release of Ca2+ from intracellular stores. Additionally, these Ca(2+)-activated Cl currents (ICl(Ca)) can be activated by raising intracellular Ca2+ through artificial experimental procedures such as intracellular photorelease of Ca2+ from "caged" photolabile compounds (e.g. DM-nitrophen) or by treating cells with Ca2+ ionophores. The potential changes that result from activation of Ca(2+)-activated Cl- channels are dependent on resting membrane potential and the equilibrium potential for Cl-. Ca2+ entry during a single action potential is sufficient to produce substantial after potentials, suggesting that the activity of these Cl- channels can have profound effects on cell excitability. The whole cell ICl(Ca) can be identified by sensitivity to increased Ca2+ buffering capacity of the cell, anion substitution studies and reversal potential measurements, as well as by the actions of Cl- channel blockers. In cultured sensory neurones, there is evidence that the ICl(Ca) deactivates as Ca2+ is buffered or removed from the intracellular environment. To date, there is no evidence in mammalian neurones to suggest these Ca(2+)-sensitive Cl- channels undergo a process of inactivation. Therefore, ICl(Ca) can be used as a physiological index of intracellular Ca2+ close to the cell membrane. The ICl(Ca) has been shown to be activated or prolonged as a result of metabolic stress, as well as by drugs that disturb intracellular Ca2+ homeostatic mechanisms or release Ca2+ from intracellular stores. In addition to sensitivity to classic Cl- channel blockers such as niflumic acid, derivatives of stilbene (4,4'diisothiocyanostilbene-2,2'-disulphonic acid, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid) and benzoic acid (5-nitro 2-(3-phenylpropylamino) benzoic acid), ICl(Ca) are also sensitive to polyamine spider toxins and some of their analogues, particularly those containing the amino acid residue arginine. The physiological role of Ca(2+)-activated Cl- channels in neurones remains to be fully determined. The wide distribution of these channels in the nervous system, and their capacity to underlie a variety of events such as sustained or transient depolarization or hyperpolarizations in response to changes in intracellular Ca2+ and variations in intracellular Cl- concentration, suggest the roles may be subtle, but important.

Animals↗