Biomedical subjects

B Muller

Publications and source records attributed to B Muller.

At least 19 recordsLinked to original sources

PubMed2002

Dopamine transmission in DYT1 dystonia: a biochemical and autoradiographical study.

Indices of dopamine transmission were measured in the postmortem striatum of DYT1 dystonia brains. A significant increase in the striatal 3,4-dihydroxyphenylacetic acid/dopamine ratio was found. Quantitative autoradiography revealed no differences in the density of dopamine transporter or vesicular monoamine transporter-2 binding; however, there was a trend toward a reduction in D(1) receptor and D(2) receptor binding. One brain with DYT1 parkinsonism was similarly evaluated and marked reductions in striatal dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid content as well as the density of binding of all four dopaminergic ligands were measured.

Autoradiography↗

PubMed2001

Late immunoneutralization of procalcitonin arrests the progression of lethal porcine sepsis.

BACKGROUND: Procalcitonin (ProCT) is becoming increasingly recognized as a mediator as well as a marker of sepsis. Serum ProCT concentrations rise soon after induction of sepsis and remain elevated over a prolonged period of time. In contrast, many pro-inflammatory cytokines, e.g., tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), rise and decline early in the course of sepsis. Researchers have improved survival in animal models of sepsis by prophylactically blocking IL-1beta and TNF-alpha with immunotherapy, but therapeutic treatment has been less successful in clinical trials. We hypothesized that the sustained elevation of ProCT in the serum would allow for effective therapeutic immunoneutralization of this peptide late in the course of sepsis. METHODS: Lethal polymicrobial sepsis was induced in 10 castrated, male Yorkshire pigs by intraabdominal spillage of cecal contents (1 gm/kg) and intraabdominal instillation of 2 x 10(11) cfu of a toxigenic strain of E. coli (O18:K1:H7). The treated group (n = 5) received an intravenous infusion of purified rabbit antiserum to the aminoterminus of porcine ProCT. The control group (n = 5) received nonreactive, purified rabbit IgG. The purified antiserum was infused to all animals 3 h after the induction of sepsis, at which time very severe physiologic dysfunction was manifest, and many of the animals appeared to be preterminal. Physiologic and metabolic parameters were measured until death or for 15 h after induction of sepsis, at which time all surviving animals were euthanized. RESULTS: Therapeutic immunoneutralization of serum ProCT improved most measured physiologic and metabolic parameters in septic pigs. Specifically, there was a significant increase in mean arterial pressure, urine output and cardiac index in all animals treated with ProCT antibody. Serum creatinine was significantly lower in treated animals. Although acidosis was not as severe in treated animals, as indicated by higher pH values and lower lactate concentrations, these results did not achieve statistical significance. Significantly, 11 h after the induction of sepsis there was 100% mortality in the control group while only one animal in the treated group expired. CONCLUSION: The prolonged elevation of ProCT concentrations in sepsis allows neutralization of this peptide to be effective during the course of this disorder. These findings suggest that immunoneutralization of ProCT may be a useful treatment in clinical situations where sepsis is already fully established.

Animals↗

PubMed2001

Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients.

OBJECTIVE: To evaluate the recently discovered long pentraxin PTX3 in plasma of critically ill patients and to compare it with the classic short pentraxin C-reactive protein and with other indicators of inflammation. DESIGN: A cohort study on plasma samples. SETTING: Medical intensive care unit (ICU) of the University Hospital of Basel. PATIENTS: A total of 101 consecutive critically ill patients admitted to the medical ICU. INTERVENTIONS: Venous blood samples were routinely obtained at entry, on day 2, and at discharge or before death. MEASUREMENTS AND MAIN RESULTS: Plasma samples were obtained from 101 consecutive critically ill patients admitted to the ICU with systemic inflammatory response syndrome, sepsis, or septic shock. PTX3 plasma levels were measured by enzyme-linked immunosorbent assay. PTX3 was elevated in critically ill patients, with a gradient from systemic inflammatory response syndrome to septic shock. PTX3 levels correlated with clinical scores reflecting severity of disease (e.g., Acute Physiology and Chronic Health Evaluation II: p =.00097). In addition, high levels of PTX3 were associated with unfavorable outcome. CONCLUSIONS: The long pentraxin PTX3 is elevated in critically ill patients and correlates with severity of disease and infection. Compared with the short pentraxin C-reactive protein, PTX3 may be a more direct indicator of tissue involvement by inflammatory and infectious processes.

Acute-Phase Proteins↗

PubMed2001

The elongation rate at the base of a maize leaf shows an invariant pattern during both the steady-state elongation and the establishment of the elongation zone.

Spatial and temporal analyses of elongation and cell length of monocotyledon leaves have most often been performed during the period when leaves are visible and elongate at a constant rate (steady-state). In the present study, the focus was on the earlier stages, during the establishment of the elongation zone. Regardless of leaf development stage, the segment located between 0 and 35 mm from the leaf insertion point had a relative elongation rate that increased with distance from insertion point ('accelerating zone') while the segment located further than 35 mm had a relative elongation rate that decreased ('decelerating zone'). This stable pattern held for both young, non-emerged leaves, where it was restricted to the portion corresponding to the length of the blade, and for leaves during steady-state elongation. In the same way, the profile of cell length was essentially the same during early development and during steady-state elongation. The results of a temporal analysis of whole-leaf elongation rate, carried out in the field and in the greenhouse at different light intensities were consistent with a time-invariant pattern of elongation. Whole-leaf relative elongation rate increased with time until the leaf reached 30-40 mm length (although at different leaf ages depending on conditions), and declined afterwards. These results suggest that the patterns governing the elongation rate of a sector of a maize leaf are independent of the leaf developmental stage but depend on sector position only.

Cell Differentiation↗

PubMed2000

Fluctuation probes of quark deconfinement

The size of the average fluctuations of net baryon number and electric charge in a finite volume of hadronic matter differs widely between the confined and deconfined phases. These differences may be exploited as indicators of the formation of a quark-gluon plasma in relativistic heavy-ion collisions, because fluctuations created in the initial state survive until freeze-out due to the rapid expansion of the hot fireball.

Journal Article↗

PubMed2000

Natural variation in immune responsiveness, with special reference to immunodeficiency and promoter polymorphism in class II MHC genes.

This review deals with natural selection operating on heterozygotes as a key factor controlling (a) the frequency of immunodeficiencies, and (b) promoter polymorphism in MHC class II genes. The known difference in frequency distribution of X-linked and autosomal deficiencies lend support to this possibility, and suggest that the frequency of neonatal defect may rise as old-established equlibria between entry and exit of deleterious mutations change. MHC class II gene promoters differ in their capacity to favor Th1 (or reciprocally Th2) responses, thus suggesting that promoter polymorphism is sustained by the greater flexibility in response that this confers on heterozygotes.

Animals↗

PubMed2000

Spatial distributions of expansion rate, cell division rate and cell size in maize leaves: a synthesis of the effects of soil water status, evaporative demand and temperature.

The spatial distributions of leaf expansion rate, cell division rate and cell size was examined under contrasting soil water conditions, evaporative demands and temperatures in a series of experiments carried out in either constant or naturally fluctuating conditions. They were examined in the epidermis and all leaf tissues. (1) Meristem temperature affected relative elongation rate by a constant ratio at all positions in the leaf. If expressed per unit thermal time, the distribution of relative expansion rate was independent of temperature and was similar in all experiments with low evaporative demand and no water deficit. This provides a reference distribution, characteristic of the studied genotype, to which any distribution in stressed plants can be compared. (2) Evaporative demand and soil water deficit affected independently the distribution of relative elongation rate and had near-additive effects. For a given stress, a nearly constant difference was observed, at all positions of the leaf, between the relative elongation rates of stressed plants and those of control plants. This caused a reduction in the length of the zone with tissue elongation. (3) Methods for calculating cell division rate in the epidermis and in all leaf tissues are proposed and discussed. In control plants, the zone with cell division was 30 mm and 60 mm long in the epidermis and in whole tissues, respectively. Both this length and relative division rate were reduced by soil water deficit. The size of epidermal and of mesophyll cells was nearly unaffected in the leaf zone with both cell division and tissue expansion, suggesting that water deficit affects tissue expansion rate and cell division rate to the same extent. Conversely, cell size of epidermis and mesophyll were reduced by water deficit in mature parts of the leaf.

Cell Division↗

PubMed2000

Procalcitonin and proinflammatory cytokine interactions in sepsis.

Immunoneutralization of procalcitonin (ProCT), a putative mediator of sepsis, has been shown to increase survival in an animal model of sepsis. To better understand the role that ProCT plays in the sepsis cascade, we studied the relationship of this hormone to the proximal proinflammatory mediators, IL-1beta and TNFalpha. Hamsters were made septic by i.p. implantation of Escherichia coli-impregnated agar pellets. A time line study of serum IL-beta, TNFalpha, and ProCT levels showed that the increase in the cytokines was transient and less than 2-fold over baseline, whereas ProCT increased >100-fold by 12 h and remains elevated through 24 h. TNFalpha (400 microg/kg) was injected into healthy animals, inducing an elevation in ProCT that was 25-fold greater than controls. ProCT (30 microg/kg) was given to healthy and septic animals. In healthy animals, there was no significant elevation in serum IL-1beta or TNFalpha levels. In septic animals, IL-1beta was modestly blunted at 3 h but not at 12 h, and there was no change in TNFalpha levels. ProCT did not initiate or enhance IL-1beta or TNFalpha expression; however, the massive and sustained elevation of this hormone seen in sepsis can be induced by the proximal cytokine, TNFalpha. This study suggests that ProCT is a secondary mediator that might augment and amplify but does not initiate the septic response. Immunoneutralization of ProCT may prove to be an important clinical strategy, in view of its sustained elevation and the difficulty in initiating therapy for sepsis during the early phases of illness.

Animals↗

PubMed2000

Adventitia-derived nitric oxide in rat aortas exposed to endotoxin: cell origin and functional consequences.

The role of adventitial cells in bacterial lipopolysaccharide (LPS)-induced vascular nitric oxide (NO) overproduction has been largely ignored. In rat aortas exposed to LPS in vitro or in vivo, it was found that adventitia contained the major part of NO synthase (NOS)-2 protein (Western blot and immunohistochemistry) and generated the largest amount of NO (electron paramagnetic resonance spin trapping). NOS-2 immunoreactive cells were mainly resident macrophages at an early stage (5 h, in vitro or in vivo) and fibroblasts at a later stage (20 h, in vitro). Adventitial NOS-2 activity largely accounted for 1) the relaxing effect of L-arginine in rings exposed to LPS in vivo, 2) generation of an "NO store" revealed by N-acetylcysteine-induced relaxation, and 3) formation of protein-bound dinitrosyl iron complexes in the medial layer of aortic rings exposed to LPS in vitro. In conclusion, the adventitia is a powerful source of NO triggered by LPS in the rat aorta. This novel source of NO has an important impact on smooth muscle function and might be implicated in various inflammatory diseases.

Animals↗

PubMed2000

Inducible NO synthase activity in blood vessels and heart: new insight into cell origin and consequences.

Induction of the inducible form of nitric oxide synthase (iNOS) in the vascular and cardiac tissue by several inflammatory stimuli may result in the production of large amounts of nitric oxide (NO) for a sustained period. Recent data obtained in the rat aorta in which iNOS was induced by lipopolysaccharide (LPS) have demonstrated that adventitial cells represent the main site of NO production. Adventitial-derived NO can exert an immediate down-regulatory effect on smooth muscle contraction (via activation of the cyclic GMP pathway) but may also initiate longer lasting effects through the formation of NO stores within the medial layer. One candidate for such NO stores are dinitrosyl non-heme iron complexes. Low molecular weight thiols interact with preformed NO stores and promote vasorelaxation by a cyclic GMP-independent mechanism involving the activation of potassium channels. In the heart, the induction of iNOS is involved in delayed protection against ischemia-reperfusion-induced functional damages. Recent data obtained with monophosphoryl lipid A, a non-toxin derivative of LPS, strongly suggest that iNOS-derived NO in the rat heart does not act as an immediate mediator of the cardioprotection but rather as a trigger of long-term protective mechanisms. Thus, the present data reveal the important role of adventitial cells as a site of iNOS expression and activity in intact blood vessels. The induction of adaptive mechanisms in the heart and the formation of releasable NO stores in blood vessels are examples of long-term consequences of iNOS induction. These new information are relevant for a better understanding of the circumstances in which NO overproduction by iNOS may play either a beneficial or deleterious role in these tissues.

Animals↗

PubMed1999

Dioclein, a new nitric oxide- and endothelium-dependent vasodilator flavonoid.

In the present work, the vasorelaxant effect of dioclein, a new flavonoid isolated from Dioclea grandiflora (Leguminoseae), was investigated in the rat aorta. Dioclein induced a concentration-dependent relaxation in vessels pre-contracted with phenylephrine (IC(50)=1.3+/-0.3 microM), a response which was abolished after endothelium removal. Neither indomethacin (10 microM), an inhibitor of cyclo-oxygenase, nor atropine (1 microM), an antagonist of muscarinic receptors, modified the effect of dioclein. Dioclein (30 microM) induced a significant increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in aortic rings with endothelium. The nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine-methyl-ester (L-NAME, 300 microM), strongly inhibited or abolished the relaxing effect and rise in cyclic GMP levels induced by dioclein. Furthermore, dioclein (30 microM) had no effect on the endothelium-independent relaxation produced by the NO donor, 3-morpholino-sydnonimine (SIN-1), while superoxide dismutase (100 U ml(-1)) significantly potentiated it. These results indicate that, in the rat aorta, dioclein induces a NO- and endothelium-dependent vasorelaxant effect, which is associated with cyclic GMP elevation. This vasorelaxation likely results from enhanced synthesis of NO rather than enhanced biological activity of NO.

Animals↗

PubMed1999

The inducible nitric oxide synthase in vascular and cardiac tissue.

Expression of the inducible form of nitric oxide synthase (iNOS) has been reported in a variety of cardiovascular diseases. The resulting high output nitric oxide (NO) formation, besides the level of iNOS expression, depends also on the expression of the metabolic pathways providing the enzyme with substrate and cofactor. NO may trigger short and long term effects which are either beneficial or deleterious, depending on the molecular targets with which it interacts. These interactions are governed by local factors (like the redox state). In the cardiovascular system, the major targets involve not only guanylyl cyclase, but also other haem proteins, protein thiols, iron-non-haem complexes, and superoxide anion (forming peroxynitrite). The latter has several intracellular targets and may be cytotoxic, despite the existence of endogenous defence mechanisms. These interactions may either trigger NO effects or represent releasable NO stores, able to buffer NO and prolong its effects in blood vessels and in the heart. Besides selectively inhibiting iNOS, a number of other therapeutic strategies are conceivable to alleviate deleterious effects of excessive NO formation, including peroxynitrite (ONOO-) scavenging and inhibition of metabolic pathways triggered by ONOO-. When available, these approaches might have the advantage to preserve beneficial effects of iNOS induction. Counteracting vascular hyper-responsiveness to endogenous vasoconstrictor agonists in septic shock, or inducing cardiac protection against ischaemia-reperfusion injury are examples of such beneficial effects of iNOS induction.

Animals↗

PubMed1999

An independent pilot study into the accuracy and reliability of home blood glucose monitors.

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Blood Glucose Self-Monitoring↗

PubMed1999

Role diversification in the education of advanced practice psychiatric nurses.

The mode, location, and focus of health care services are changing rapidly, especially delivery of psychiatric services. The high prevalence of psychiatric and medical comorbidity, the national shift in health care to a managed care arrangement with one professional designated as principle provider, and problems with access to comprehensive services for individuals with psychiatric problems interact to create a compelling need for a clear definition of advanced psychiatric-mental health nursing practice. This article is, in part, a response to the national dialogue and debate sparked by the beginning development of a psychiatric nurse practitioner certification exam. However, this debate will be used merely as a starting point to articulate and document the need for a flexible, diverse, and evolving definition of advanced psychiatric-mental health nursing practice that can inform and shape educational programs in the discipline.

Connecticut↗

PubMed1999

Triggering role of nitric oxide in the delayed protective effect of monophosphoryl lipid A in rat heart.

1. The main objective of the present study was to further evaluate the role of nitric oxide (NO) in delayed cardiac protection against ischaemia-reperfusion injury induced by monophosphoryl lipid A (MLA). 2. For this purpose, rats were administered with either 0.5 or 2.5 mg kg(-1) MLA (i.p.). Eight or 24 h later, in vivo NO production in the heart was analysed by electron paramagnetic resonance (EPR) spin trapping technique. In parallel experiments, hearts were removed and perfused according to Langendorff. Functional ventricular parameters and incidence of ventricular fibrillation (VF) were determined after 30 min global ischaemic insult (37 degrees C) followed by 30 min reperfusion. Vascular reactivity of aortic rings was also assessed. 3. Hearts from rats pretreated with 2.5 mg kg(-1) MLA for 24 h (but not those from rats treated with 0.5 mg kg(-1) MLA for 8 and 24 h, or with 2.5 mg kg(-1) MLA for 8 h) exhibited preservation of ventricular function (LVDP, +/-dP/dtmax) and a reduced incidence of VF (25% vs 87.5% in vehicle control) during reperfusion. At the cardioprotective dose of 2.5 mg kg(-1) (for 8 or 24 h), MLA did not produce alterations of the contractile response of aortic rings to noradrenaline. 4. An increased formation of NO was detected in hearts removed from rats pretreated with 2.5 mg kg(-1) MLA for 8 h, but not in those from rats treated for 24 h (or with 0.5 mg kg(-1) MLA). 5. Pretreatment of the animals with the inhibitors of inducible NO-synthase, aminoguanidine (2x300 mg kg(-1)) or L-N6-(1-Iminoethyl)-lysine (L-NIL, 10 mg kg(-1)) abolished both MLA (2. 5 mg kg(-1))-induced rise of NO production (observed 8 h after MLA) and cardioprotection (observed 24 h after MLA). However MLA-induced cardioprotection was not attenuated when the hearts were perfused with aminoguanidine (150 microM) for 30 min before the ischaemic insult. 6. Altogether, the present data suggest that NO acts as a trigger rather then a direct mediator of the delayed cardioprotective effect of MLA in rat heart.

Adjuvants, Immunologic↗

PubMed1999

Splenic lymphoma with villous lymphocytes presenting as leucocytoclastic vasculitis.

We describe a 69-year-old woman who presented with purpura on the legs. Examination of a blood film revealed a homogenous population of abnormal lymphoid cells with villous projections. The immunophenotype was consistent with a diagnosis of splenic lymphoma with villous lymphocytes (SLVL). A type II (IgM-IgG) cryoglobulin was detected in the serum. Renal biopsy demonstrated a membranoproliferative type I glomerulonephritis with intraluminal IgG and IgM deposits, and a skin biopsy showed a leucocytoclastic vasculitis with outlining of the vessels by IgG and IgM. Vasculitis has been reported in association with a number of haematological malignancies, most frequently with hairy cell leukaemia. To our knowledge this is the first report of SLVL presenting with cryoglobulinaemic vasculitis.

Aged↗

PubMed1999

Procalcitonin and proinflammatory cytokine in interactions in sepsis.

Animals↗

PubMed1999

Effect of growth temperature on hydrolytic and esterifying activities from pseudomonas fragi CRDA 037 grown on whey

The production of hydrolytic and esterifying activities of Pseudomonas fragi CRDA 037 grown on a whey-based medium was investigated at different temperatures over time. The optimal temperature was found to be critical and different for the production of both activities. The highest hydrolytic activity was detected with bacteria cultivated at between 24 degrees C (149.2 U/liter) and 27 degrees C (133.8 U/liter), while the highest production of ethyl valerate (esterifying activity) was observed by using biomass grown at 15 degrees C (0.75 U/liter). When the fermentation temperature was increased, the incubation time necessary to reach the maximal concentration of both activities was reduced. Studies of the thermostability of both activities showed that the hydrolytic activity was more stable than the esterifying activity at 15 and 24 degrees C. Statistical analysis allowed the determination of the equations that predicted the production of hydrolytic and esterifying activities as a function of time and growth temperature. The optimal assay temperatures for the hydrolytic and esterifying activities were 37 degrees C and 12 to 15 degrees C, respectively.

Journal Article↗