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Biomedical subjects

D J Martin

Publications and source records attributed to D J Martin.

At least 37 records · Page 2Linked to original sources

The maize golden2 gene defines a novel class of transcriptional regulators in plants.

In the C4 plant maize, three photosynthetic cell types differentiate: C4 bundle sheath, C4 mesophyll, and C3 mesophyll cells. C3 mesophyll cells represent the ground state, whereas C4 bundle sheath and C4 mesophyll cells are specialized cells that differentiate in response to light-induced positional signals. The Golden2 (G2) gene regulates plastid biogenesis in all photosynthetic cells during the C3 stages of development. However, G2 function is specifically committed to the differentiation of bundle sheath cell chloroplasts in C4 leaf blades. In this article, we report the isolation of G2-like (Glk) genes from maize and rice, providing evidence for a family of Glk genes in plants. The expression profiles of the rice Glk genes suggest that these genes may act redundantly to promote photosynthetic development in this C3 species. In maize, G2 and ZmGlk1 transcripts accumulate primarily in C4 bundle sheath and C4 mesophyll cells, respectively, suggesting a specific role for each gene in C4 differentiation. We show that G2 and ZmGLK1 both can transactivate reporter gene transcription and dimerize in yeast, which supports the idea that these proteins act as transcriptional regulators of cell-type differentiation processes.

Amino Acid Sequence↗

Role of Ca2+ stores in metabotropic L-glutamate receptor-mediated supralinear Ca2+ signaling in rat hippocampal neurons.

The role of metabotropic l-glutamate (mGlu) receptors in supralinear Ca(2+) signaling was investigated in cultured hippocampal cells using Ca(2+) imaging techniques and whole-cell voltage-clamp recording. In neurons, but not glia, global supralinear Ca(2+) release from intracellular stores was observed when the mGlu receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) was combined with elevated extracellular K(+) levels (10.8 mm), moderate depolarization (15-30 mV), or NMDA (3 micrometer). There was a delay (2-8 min) before the stores were fully charged, and the enhancement persisted for a short period (up to 10 min) after removal of the store-loading stimulus. Studies with the mGlu receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine demonstrated that these effects were mediated by activation of the mGlu(5) receptor subtype. The L-type voltage-gated Ca(2+) channel antagonist nifedipine (10 micrometer) substantially reduced responses to DHPG obtained in the presence of elevated extracellular K(+) but not NMDA. This suggests that the Ca(2+) that is required to load the stores can enter either through L-type voltage-gated Ca(2+) channels or directly through NMDA receptors. The findings that both depolarization and NMDA receptor activation can facilitate mGlu receptor Ca(2+) signaling adds considerable flexibility to the processes that underlie activity-dependent changes in synaptic strength. In particular, a temporal separation between the store-loading stimulus and the activation of mGlu receptors could be used as a recency detector in neurons.

Action Potentials↗

Mobilisation of intracellular Ca2+ by mGluR5 metabotropic glutamate receptor activation in neonatal rat cultured dorsal root ganglia neurones.

The ability of metabotropic glutamate receptor activation to mobilise intracellular calcium was investigated in cultured dorsal root ganglion (DRG) neurones from neonatal rats using the calcium sensitive fluorescent dye Fura-2. L-glutamate (10 microM) caused sustained and oscillatory increases in intracellular calcium concentration ([Ca2+]i) in a subpopulation of cultured DRG neurones. The oscillatory responses were not blocked by combined application of the ionotropic glutamate receptor antagonists MK 801 (2 microM) and CNQX (20 microM). Oscillations in [Ca2+]i were also observed following application of the nonselective metabotropic glutamate receptor (mGluR) agonist, trans-(1S,3R)-1-aminocyclopentane-1S, 3R-dicarboxylic acid (1S,3R)-ACPD, 20 microM) and the mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 500 microM). These responses were blocked by the selective Group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) (100 microM) and Ca2+ release channel inhibitors ryanodine (100 microM) and dantrolene (10 microM). The predominantly Group II agonist (2S,2'R,3'R)-2-(2'3'-dicarboxy-cyclopropyl)glycine (DCG-IV, 100 microM) failed to produce Ca2+ transients alone but suppressed responses to CHPG. Reverse transcriptase PCR techniques, using primers specific to Group I mGluRs, revealed the presence of mGluR5 but not mGluR1 mRNA in these cells. Therefore, glutamate can cause a slowly activating and reversible mobilisation of [Ca2+]i in sensory neurones by activation of ionotropic receptors, and can induce oscillatory calcium transients by selectively activating metabotropic glutamate receptors that are likely to be of the mGluR5 subtype.

Animals↗

Polydimethylsiloxane/polyether-mixed macrodiol-based polyurethane elastomers: biostability.

A series of four thermoplastic polyurethane elastomers were synthesized with varying proportions of poly(hexamethylene oxide) (PHMO) and poly(dimethylsiloxane) (PDMS) macrodiols. The macrodiol ratios (by weight) employed were (% PDMS:% PHMO) 100:0, 80:20, 50:50 and 20:80. The weight fraction of macrodiol in each polymer was fixed at 60%. The mixed macrodiols were reacted with 4,4'-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol (BDO) chain extender. The biostability of these polymers was assessed by strained subcutaneous implantation in sheep for three months followed by microscopic examination. Pellethane 2363-80A and 2363-55D were employed as control materials. The mechanical properties of the polymers were tested and discussed along with the biostability results. The results showed that soft, flexible PDMS-based polyurethanes with very promising biostability can be successfully produced using the mixed macrodiol approach. The formulation with 80% PDMS macrodiol produced the best result in terms of a combination of flexibility, strength and biostability.

Biocompatible Materials↗

Relation of therapeutic alliance and perfectionism to outcome in brief outpatient treatment of depression.

Prior analyses of the National Institute of Mental Health Treatment of Depression Collaborative Research Program demonstrated that perfectionism was negatively related to outcome, whereas both the patient's perception of the quality of the therapeutic relationship and the patient contribution to the therapeutic alliance were positively related to outcome across treatment conditions (S. J. Blatt, D. C. Zuroff, D. M. Quinlan, & P. A. Pilkonis, 1996; J. L. Krupnick et al., 1996). New analyses examining the relations among perfectionism, perceived relationship quality, and the therapeutic alliance demonstrated that (a) the patient contribution to the alliance and the perceived quality of the therapeutic relationship were independent predictors of outcome, (b) perfectionistic patients showed smaller increases in the Patient Alliance factor over the course of treatment, and (c) the negative relation between perfectionism and outcome was explained (mediated) by perfectionistic patients' failure to develop stronger therapeutic alliances.

Adult↗

Successful lysis of an obstructive aortic and renal artery thrombus in a neonate on extracorporeal membrane oxygenation.

We describe a neonate on venoarterial extracorporeal membrane oxygenation (ECMO) with acute renal failure associated with extensive aortic and bilateral renal artery thrombosis. Concurrent anticoagulation and continuous systemic thrombolytic therapy with tissue plasminogen activator (t-PA) resulted in complete thrombolysis as evaluated by Doppler flow. The relative risk and benefits of thrombolytic therapy in heparinized patients undergoing ECMO needs to be further studied.

Aortic Diseases↗

Interleukin-8 fails to induce human immunodeficiency virus-1 expression in chronically infected promonocytic U1 cells but differentially modulates induction by proinflammatory cytokines.

This study addresses the role of interleukin (IL)-8, a CXC-chemokine, the level of which is reported to be raised in the peripheral circulation of human immunodeficiency virus-1 (HIV-1)-infected individuals, during the induction of HIV-1 expression from latency and during cytokine-mediated HIV-1 up-regulation. IL-8 at the higher concentrations tested (> or = 100 ng/ml) was unable to induce HIV-1 expression in the chronically infected promonocytic U1 cell line, as measured by p24 antigen enzyme-linked immunosorbent assay (ELISA), whereas at lower concentrations of 1 and 10 ng/ml, constitutive HIV-1 expression was only marginally reduced. HIV-1 replication in acutely infected U937 cells was also significantly reduced by IL-8. The potent up-regulation of HIV-1 expression in U1 cells by tumour necrosis factor-alpha (TNF-alpha) remained unaffected by the addition of IL-8. HIV-1 induction by IL-1beta, IL-6 and TNF-beta, cytokines grouped here as intermediate HIV-1 inducers, was suppressed by IL-8 at concentrations of 1 and 10 ng/ml. However, IL-8 at 100 ng/ml did not significantly alter the effect of IL-1beta, synergized with IL-6 in enhancing, and marginally suppressed TNF-beta-induced HIV-1 expression. IL-8 suppressed granulocyte-macrophage colony-stimulating factor (GM-CSF) and enhanced interferon-gamma (IFN-gamma)-induced HIV-1 expression in a dose-dependent manner. Pretreatment of U1 cells with IL-8 did not alter the IL-8-mediated effects on cytokine-induced HIV-1 expression, suggesting that this chemokine exerts its effect at the time of HIV-1 induction or at a postinduction stage. Furthermore, IL-8 was itself induced by cytokines that up-regulate HIV-1 expression in U1 cells and the levels produced correlated directly with the levels of p24 antigen produced, suggesting common pathways for cytokine induction of both HIV-1 and IL-8. These results show that IL-8, typically a non-inducer, can differentially modulate HIV-1 expression in U1 cells and that this is dependent on the inducing cytokine and on the concentration of IL-8.

Acute Disease↗

C- and Adelta-fibre mediated thermal perception: response to rate of temperature change using method of limits.

Studies investigating the effect of rate of temperature change on thermal thresholds have used a variety of different methods and threshold combinations, and many display incomplete reporting of statistical analyses. It has been suggested that C- and Adelta-fibre mediated thresholds differ in their reaction to different rates of temperature change. Ten healthy female volunteers (aged 18-26 years; mean 21 +/- S.D. 2.53) undertook cold sensation (CS), warm sensation (WS), cold pain (CP) and heat pain (HP) threshold determinations on the thenar eminence of the dominant hand. Rates of temperature change of 0.5, 1, 2.5 and 4 degrees C/s were used, with a modified method of limits. Adaptation temperature was 32 degrees C and thermode size 3 cm x 3 cm. Results showed a significant increase in WS, HP and CP thresholds with increased rates of temperature change (all p < 0.001), but no significant change for CS (p = 0.653). These results suggest that thresholds with a C-fibre component (WS, HP and CP) and those that are Adelta-fibre mediated (CS) behave differently. A traditional explanation of measurement artefact alone is insufficient in rationalizing these results, with additional factors potentially involved. Slow rates of temperature change were shown to reduce mean intra-individual differences in recorded threshold values, and also to abolish ceiling effects with HP threshold determinations. Clinically, therefore, using slow rates of temperature change with method of limits has a range of benefits over and above simply minimizing measurement artefact.

Adaptation, Physiological↗

Barriers to antiretroviral adherence among HIV-infected adults.

Success of highly active antiretroviral therapies (HAART) relies on HIV-infected patients being able to adhere to complicated treatment regimens for extremely long periods of time. Four focus groups with patients taking antiretrovirals (N = 39) were conducted to: (1) determine what strategies facilitate successful adherence; (2) determine what barriers prevent adherence; and (3) investigate the health-care provider and patient relationship and how it may impact adherence. Quantitative and qualitative information was gathered. Participants were prescribed an average of 15 pills per day (M = 14.7, SD = 6.3, range 4 to 36). Findings from the quantitative data revealed that the three strategies used most often to aid adherence were: carrying special containers for medication; having a health-care provider explain or clarify medication requirements; and carrying food and water for adherence to special instructions. The most difficult barriers for patients were sleeping through dose time, problems in following special instructions, and changes in daily routines. From the qualitative data, four main categories of barriers and aids to adherence emerged: patient characteristics, the health-care provider-patient relationship, the health-care system, and issues related to the medication regimen. Barriers related to the health care provider-patient relationship included patient satisfaction with their provider, as well as quality of communication with the provider. In addition, health-care system barriers caused difficulty in maintaining adherence. Implications for patient as well as provider interventions are discussed.

Adult↗

Effects of ZK-807834, a novel inhibitor of factor Xa, on arterial and venous thrombosis in rabbits.

Inhibition of factor Xa (FXa) may interrupt thrombus progression. This study compared the antithrombotic activity of a novel FXa inhibitor, ZK-807834 [MW, 527 D; Ki (human FXa), 0.11 nM], with recombinant tick anticoagulant peptide [rTAP; MW, 6,685 D; Ki, (human FXa) = 0.28 nM], and DX-9065a [MW 445 D, Ki (human FXa), 40 nM] in rabbits with arterial thrombosis induced by electrical vascular injury. ZK-807834 also was compared with low molecular weight heparin (LMWH; MW, 5,500 D) during venous thrombosis induced by placing a copper wire and threads in the vena cava. Inhibitors were administered as an i.v. bolus and 2-h infusion. Total dosages of ZK-807834, > or =0.7 micromol/kg (n = 18); rTAP, > or =1 micromol/kg (n = 18); or DX-9065a, > or =11 micromol/kg (n = 18) decreased the incidence of arterial thrombotic occlusion compared with control animals (p < 0.05). However, five of six animals given the lowest effective dosage of rTAP and four of six animals given DX-9065a bled from a surgical incision >5 min, but only two of six animals given ZK-807834 bled >5 min. Venous clot weights were reduced compared with controls for dosages of ZK-807834 > or =0.007 micromol/kg (n = 36) or LMWH > or =0.2 micromol/kg (n = 18). Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were unchanged from baseline at the minimally effective dose of ZK-807834, whereas aPTT was increased twofold at the effective dose of LMWH. Thus ZK-807834 may be useful to attenuate thrombosis at lower dosages and with less perturbation of systemic hemostasis compared with available agents.

Amidines↗

Functional and morphological modifications of the urinary bladder in aging female rats.

In female Wistar/Rij rats, 10 and 30 mo old, the micturition profiles in conscious animals, the contractile responses of the isolated urinary bladder, and the histology of the vesical tissue have been investigated. During cystomanometry, 60% of conscious senescent rats, but only 25% of young adult rats, showed spontaneous contractions during the bladder-filling phase. In aging rats, micturition pressure and duration of micturition were significantly higher by approximately 40-50%. In contrast, bladder capacity, bladder compliance, micturition volume, and residual volume were not modified with age. In vitro, the contractile responses of the bladder body to KCl, carbachol, arecoline, and alpha,beta-MeATP were similar in tissues from young adult and senescent rats. In contrast, maximum responses to noradrenaline, but not phenylephrine, were two times greater in the older rats. Isoprenaline exhibited the same potency in relaxing KCl-precontracted bladder body of 10- and 30-mo-old animals. Morphometric analysis showed a significant increase in the mean thickness of the muscularis layer with age, whereas the collagen density significantly decreased in the muscularis and in the lamina propria layers. The fact that the majority of senescent rats displayed bladder instability and increased response to alpha-adrenergic agonists suggests that this strain of rat seems a good model for the aged human. However, other characteristics of the aging human urinary tract (urinary frequency, decreased cystometric capacity, and decreased detrusor contractility associated with fibrosis) are not present.

Adenosine Triphosphate↗

Relation of the therapeutic alliance with outcome and other variables: a meta-analytic review.

To identify underlying patterns in the alliance literature, an empirical review of the many existing studies that relate alliance to outcome was conducted. After an exhaustive literature review, the data from 79 studies (58 published, 21 unpublished) were aggregated using meta-analytic procedures. The results of the meta-analysis indicate that the overall relation of therapeutic alliance with outcome is moderate, but consistent, regardless of many of the variables that have been posited to influence this relationship. For patient, therapist, and observer ratings, the various alliance scales have adequate reliability. Across most alliance scales, there seems to be no difference in the ability of raters to predict outcome. Moreover, the relation of alliance and outcome does not appear to be influenced by other moderator variables, such as the type of outcome measure used in the study, the type of outcome rater, the time of alliance assessment, the type of alliance rater, the type of treatment provided, or the publication status of the study.

Humans↗

Alteration of interferential current and transcutaneous electrical nerve stimulation frequency: effects on nerve excitation.

OBJECTIVES: To investigate the effects of different interferential current (IC) and transcutaneous electrical nerve stimulation (TENS) frequencies on sensory, motor, and pain thresholds. STUDY DESIGN: Single blind, repeated measures design. SETTING: Laboratory. PARTICIPANTS: Women students 18 to 30 years old (n = 24). INTERVENTIONS: Premodulated IC and square-wave TENS pulses (125micros phase duration) were applied over the median nerve at a range of frequencies in all subjects. MAIN OUTCOME MEASURES: The peak current (in milliamperes) was recorded twice at each threshold for each frequency, and averaged. RESULTS: Both IC and TENS displayed a statistically significant effect of frequency for each threshold. However, frequency effects with IC were not well defined and were of small magnitude. Pure 4kHz current (0Hz amplitude modulated frequency) with IC did not produce effects different from those produced when an amplitude modulated frequency was included. With TENS, frequency effects were very clearly observed, with a distinct increase in the current intensity at each threshold as frequency decreased. CONCLUSIONS: It is postulated that the medium frequency component of IC is the main parameter in stimulation, contrary to traditional claims of the amplitude modulated frequency being important. TENS was shown to be a more adaptable method of stimulating these nerve pathways than IC.

Adolescent↗

Does early ultrasonography affect management of pediatric appendicitis? A prospective analysis.

BACKGROUND: Appendicitis remains a difficult diagnosis in children. Ultrasonography is increasingly used for the diagnosis of appendicitis, although the proper clinical role for this test remains unclear. METHODS: To evaluate the clinical utility of ultrasonography in appendicitis, the authors analyzed prospectively all children evaluated for possible appendicitis from January 1 through December 31, 1997. Children with a high clinical suspicion of appendicitis were referred for surgery (n = 122). Children with equivocal findings of appendicitis were referred for early ultrasonography (EUS) and formed the study cohort (n = 103). An initial management plan was made to operate or observe each patient, and a risk of appendicitis (doubtful, possible, probable) was assigned by a pediatric surgery fellow. EUS was then performed, and its effect on management was assessed. RESULTS: Using clinical judgment to operate at initial presentation, the sensitivity was 38% and specificity was 95%. Using EUS alone, the sensitivity was 87% and specificity was 88%. The management of 30 of 103 patients (30%) was changed after EUS, including a decision to operate in 28 patients and a decision not to operate in two patients. CONCLUSIONS: EUS appears to have substantial clinical utility in children with equivocal findings of appendicitis, and its use complements the clinical management. The use of EUS can improve patient care and reduce hospital resource utilization.

Adolescent↗