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J Lang

Publications and source records attributed to J Lang.

At least 109 records · Page 6Linked to original sources
PubMed1999

Alpha2-adrenoceptor agonists stimulate high-affinity GTPase activity in a receptor subtype-selective manner.

Transfected Chinese hamster ovary cells expressing human alpha2A-, alpha2B- and alpha2C-adrenoceptor subtypes were used to monitor alpha2-adrenoceptor-stimulated GTP hydrolysis. Incubation with 100 microM (-)-adrenaline resulted in stimulation of pertussis toxin-sensitive GTPase by 380% after activation of the alpha2A-subtype, by 320% after activation of the alpha2B-subtype and by 110% after activation of the alpha2C-subtype. The agonists dexmedetomidine, UK14,304 (5-bromo-6-[2-imidazoline-2-ylamino]quinoxaline) and oxymetazoline showed subtype-dependent efficacy. Dexmedetomidine was a full agonist at the alpha2B-subtype and a partial agonist at the alpha2A- and the alpha2C-subtypes. UK14,304 was a full agonist at the alpha2A-subtype and a partial agonist at the other two. Oxymetazoline showed strong partial agonism at the alpha2B-subtype (63% of adrenaline), but did not significantly activate the alpha2A- and the alpha2C-subtypes. These results agreed with cAMP accumulation experiments carried out with cell lines endogenously expressing the alpha2A-subtype (human erythroleukemia, HEL) or the alpha2B-subtype (neuroblastoma-glioma, NG108-15). The GTPase assay may thus provide a valuable tool for the identification of subtype-selective alpha2-adrenoceptor agonists.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1999

Encapsulation of Inorganic Particles by Dispersion Polymerization in Polar Media.

Following a previous work (Bourgeat-Lami, E., and Lang, J., J. Colloid Interface Sci. 197, 293 (1998)), encapsulation of silica beads has been achieved by dispersion polymerization of styrene in an aqueous ethanol medium using poly(N-vinyl pyrrolidone) as stabilizer. Silica beads, prepared according to the Stöber method, were coated prior to polymerization by grafting 3-(trimethoxysilyl)propyl methacrylate onto the surface. A great number of silica beads per composite particle were previously found using beads that had diameters between 49 and 120 nm. In the present work, larger silica beads with diameters between 191 and 629 nm are investigated. We demonstrate by transmission electron microscopy that, consequently, only a small number of silica beads are contained in the composite particles. By counting the composite particles containing precisely zero, one, two, three, four, and more than four silica beads, it clearly appears that the encapsulation of only one silica bead can be obtained simply by increasing the size of the beads. Under our experimental conditions, the optimal bead diameter for achieving composite particles containing only one silica bead turns out to be around 450 nm. We show that increasing the silica bead size above this value results in an increased number of composite particles without silica beads. In contrast, the number of composite particles with two, three, four, or more than four silica beads increases with decreasing silica bead size. In addition to the above variations in composition of the composite particles, changes in particle shapes were also observed as a function of the size of the silica beads and the styrene concentration in the polymerization medium. Hypotheses concerning these variations are presented. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Acute effects of the selective cholinergic channel activator (nicotinic agonist) ABT-418 in Alzheimer's disease.

To explore further the potential for cognitive enhancement utilizing nicotinic stimulation in Alzheimer's disease (AD), six otherwise healthy subjects with moderate AD received placebo and three doses (6, 12, and 23 mg) of the novel selective cholinergic channel activator (ChCA) (nicotinic agonist) ABT-418 over 6 h in a double-blind, within-subjects, repeated-measures design. Subjects showed significant improvements in total recall and a decline in recall failure on a verbal learning task. Qualitatively similar improvements were seen in non-verbal learning tasks such as spatial learning and memory, and repeated acquisition. No significant behavioral, vital sign, or physical side effects were seen. These results confirm that stimulating central nicotinic receptors has acute cognitive benefit in AD patients. These findings suggest that selective ChCAs have a potential therapeutic role in dementing disorders, and that further studies with this or similar agents in AD and/or Parkinson's disease are warranted.

Aged↗
PubMed1999

Cytokine gene expression following neural grafts.

A reverse-transcription polymerase chain reaction study of molecular events following solid neural tissue xenogeneic and syngeneic grafts into the mouse caudate nucleus was made between 1 day and 30 days post-grafting. Constitutive expression of interleukin (IL)-1 and transforming growth factor (TGF)-beta1 mRNAs was detected. The sham operation produced minimal cytokine upregulation, indicating that surgical trauma caused minimal damage. A similar picture was seen with syngeneic grafts, which showed good graft survival. Xenografts, however, were rejected within 30 days and cytokine mRNAs for IL-2, IL-2R, IL-4, IL-10 and interferon (IFN)-gamma were detected from 7 days post-graft, correlating with histological identification of a leukocytic infiltrate. This method provides a quick, comparative screen for detecting cytokine mRNA profiles in neural grafts and may assist the diagnosis of early rejection phenomena. As such, it is a potential analytical tool for strategies aimed at depleting/blocking the activity of different cell types and/or cytokines in future neural transplant therapy.

Animals↗
PubMed1999

Neutralization, by a monospecific Bothrops lanceolatus antivenom, of toxic activities induced by homologous and heterologous Bothírops snake venoms.

A monospecific Bothrops lanceolatus antivenom, currently used in Martinique, was tested for its efficacy in the neutralization of several toxic and enzymatic activities of the venoms of B. lanceolatus, B. atrox and B. asper. When tested by the i.p. route in mice, B. lanceolatus venom had an LD50 of 12.8 microg/g. In addition, it induced local tissue damage (hemorrhage, edema and myotoxicity) and showed indirect hemolytic activity, but was devoid of coagulant effect on human plasma in vitro and of defibrinating activity in mice. Antivenom was fully effective in the neutralization of lethal, hemorrhagic, edema-forming, myotoxic and indirect hemolytic effects of B. lanceolatus venom in assays involving preincubation of venom and antivenom. When tested against the venoms of B. asper and B. atrox, the antivenom completely neutralized the lethal, hemorrhagic, myotoxic and indirect hemolytic effects, and was partially effective in neutralizing edema-forming activity. In contrast, the antivenom was ineffective in the neutralization of in vitro coagulant and in vivo defibrinating effects induced by these two venoms.

Animals↗
PubMed1999

Intrathoracic tracheal rupture.

This paper reports five new cases of intrathoracic tracheal rupture in cats, and summarizes these cases in conjunction with 11 cases from the literature. Most cats had no obvious respiratory signs at the time of injury, and in half of them the tracheal rupture was the only injury. The interval from trauma to onset of dyspnoea ranged from 1 to 28 days (median 12.5 days). Radiographic findings include loss of continuity of the trachea, often with a gas-filled diverticulum present between separated tracheal rings. With careful attention to surgical technique and anaesthetic management the prognosis for these cats is excellent. All eight of the cats reported in the last 14 years having surgical correction survived and returned to normal. The surgical anatomy, approach and tracheal anastomosis technique is described and recommendations for anaesthetic management are made.

Animals↗
PubMed1999

Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion.

Secretion of the peptide hormone insulin from pancreatic beta cells constitutes an important step in the regulation of body homeostasis. Insulin is stored in large dense core vesicles and released by exocytosis, a multistage process involving transport of vesicles to the plasma membrane, their docking, priming and finally their fusion with the plasma membrane. Some of the protein components necessary for this process have been identified in beta cells. The export of potent and potentially harmful substances has to be tightly controlled. The secretory response in pancreatic beta cells requires the concerted action of nutrients together with enteric hormones and neurotransmitters acting on G-protein coupled receptors. It is well established that glucose and other metabolizable nutrients depolarize the beta-cell membrane and the ensuing Ca2+ influx through voltage-dependent channels constitutes a main stimulus for insulin exocytosis. Theoretical considerations and recent observations suggest in addition an organizing role for the Ca2+ channel similar to neurotransmission. A second regulatory control on exocytosis is exerted by monomeric and heterotrimeric G-proteins. The monomeric GTPase Rab3A controls insulin secretion through cycling between a guanosine triphosphate liganded vesicle-bound form and a guanosine diphosphate liganded, cytosolic form. The effect of neurohormones is transduced by the heterotrimeric GTPases. Whereas pertussis-toxin sensitive alpha-subunits exert direct inhibition at the level of exocytosis, the Gbeta gamma-subunits are required for stimulation. It is possible that these GTPases exert immediate regulation, while protein kinases and phosphatases may modulate long-term adaptation at the exocytotic machinery itself. The molecular nature of their activators and effectors still await identification. Insights into the progression of the exocytotic vesicle from docking to fusion and how these processes are precisely regulated by proteins and second messengers may provide the basis for new therapeutic principles.

Biological Transport↗
PubMed1999

A new Vero cell rabies vaccine: results of a comparative trial with human diploid cell rabies vaccine in children.

We evaluated the immunogenicity and safety of a chromatographically purified rabies vaccine (CPRV) compared with human diploid cell rabies vaccine (HDCV) after pre-exposure immunizations (both primary and booster). Intramuscular doses of either 0.5 mL of CPRV or 1.0 mL of HDCV were given to 400 schoolchildren on days 0, 7, 28, and 365 (booster). Adequate titers of antibody (> or = 0.15 IU/mL, as defined by the Centers for Disease Control and Prevention) were observed in serum samples from all children 14 days after primary immunization with CPRV and HDCV; the antibodies persisted in all but one child up until 1 year. Fourteen days after the primary immunization series (day 42) and 7 days after booster immunization (day 372), all children had antibody titers of > or = 0.5 IU/mL. Local and systemic reactions after primary and booster immunizations occurred significantly less frequently in the CPRV group. A severe allergic reaction (angioedema) was reported in only one child after booster immunization with HDCV. CPRV has adequate immunogenicity for primary and booster pre-exposure immunizations in children and has a better safety profile than does HDCV.

Animals↗
PubMed1999

Dynamic cardiomyoplasty in patients with end-stage heart failure: anaesthetic considerations.

Dynamic cardiomyoplasty is used increasingly for patients with chronic heart failure, with approximately 500 cases having been performed. The latissimus dorsi muscle is prepared maintaining its vascular supply and the muscle flap is wrapped around the heart and connected to a cardiomyostimulator. The muscle is later stimulated synchronously with ventricular systole to augment the heart. Our experience of 22 patients with chronic heart failure (NYHA III-IV) undergoing dynamic cardiomyoplasty is described from the anaesthetist's point of view. Two patients are reported as case reports. The challenge is to manage patients with severely impaired left ventricular function, who do not obtain immediate benefit from the operation. Our experience supports the importance of early use of inotropic agents.

Adult↗
PubMed1999

Impact of nonlinear heat transfer on temperature control in regional hyperthermia.

We describe an optimization process specially designed for regional hyperthermia of deep-seated tumors in order to achieve desired steady-state temperature distributions. A nonlinear three-dimensional heat transfer model based on temperature-dependent blood perfusion is applied to predict the temperature. Using linearly implicit methods in time and adaptive multilevel finite elements in space, we are able to integrate efficiently the instationary nonlinear heat equation with high accuracy. Optimal heating is obtained by minimizing an integral objective function which measures the distance between desired and model predicted temperatures. A sequence of minima is calculated from successively improved constant-rate perfusion models employing a damped Newton method in an inner iteration. We compare temperature distributions for two individual patients calculated on coarse and fine spatial grids and present numerical results of optimizations for a Sigma 60 Applicator of the BSD 2000 Hyperthermia System.

Algorithms↗
PubMed1999

Mutational analysis of cysteine-string protein function in insulin exocytosis.

Cysteine-string proteins (Csps) are vesicle proteins involved in neurotransmission. They contain at least four domains: an N-terminal J-domain which can interact with the chaperone Hsc70, an adjacent linker region, the defining cysteine rich domain and a variable C terminus. As the relevance of these domains for the function of Csps in exocytosis is unknown, we have performed a mutational analysis of Csp domains using insulin release by large dense core vesicles (LDCVs) as a model of regulated exocytosis. All mutants were apparently palmitoylated and their subcellular distribution was similar to endogenous Csp. Point mutations within the highly conserved HPD motif of the J-domain abolished activation of Hsc70. However, these mutations altered the effect of Csp on exocytosis only after additional truncation of the extreme C terminus as found in the Csp splice variant Csp2. Furthermore, the strikingly conserved linker region adjacent to the J-domain was important for Csp function in exocytosis, but not for the activation of Hsc70 ATPase. The effects of Csp wild-type or mutants were preserved in permeabilized cells excluding an effect on transmembrane ion fluxes. These observations demonstrate a functional difference between the two isoforms and suggest a role for the J-domain co-chaperone function as well as for the newly defined linker region in LDCV exocytosis.

Cells, Cultured↗
PubMed1999

The clinical utility of invasive diagnostic techniques in the setting of ventilator-associated pneumonia. Canadian Critical Care Trials Group.

OBJECTIVE: To evaluate the clinical utility of bronchoscopy with protected brush catheter (PBC) and BAL for patients with ventilator-associated pneumonia (VAP). DESIGN: Prospective cohort study. SETTING: Ten tertiary care ICUs in Canada. PATIENTS: Ninety-two mechanically ventilated patients with a clinical suspicion of VAP who underwent bronchoscopy were compared with 49 patients with a clinical suspicion of pneumonia who did not. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We compared antibiotic use, duration of mechanical ventilation, ICU stay, and mortality. In addition, for patients who received bronchoscopy, we administered a questionnaire (before and after bronchoscopy) to evaluate the effect of PBC or BAL on (1) physician perception of the probability of VAP, (2) physician confidence in the diagnosis of VAP, and (3) changes to antibiotic management. After bronchoscopy results became available, from the physician's perspective, the diagnosis of VAP was deemed much less likely (p < 0.001), confidence in the diagnosis increased (p = 0.03), and level of comfort with the management plan increased (p = 0.02). Following the results of invasive diagnostic tests, in the group that underwent bronchoscopy, patients were receiving fewer antibiotics (31/92 vs 9/49, p = 0.05) and more patients had treatment with all their antibiotics discontinued (18/92 vs 3/49, p = 0.04) compared with the group that did not undergo bronchoscopy. Duration of mechanical ventilation and ICU stay were similar between the two groups, but mortality was lower in the group that underwent bronchoscopy with PBC or BAL (18.5% vs 34.7%, p = 0.03). CONCLUSIONS: Invasive diagnostic testing may increase physician confidence in the diagnosis and management of VAP and allows for greater ability to limit or discontinue antibiotic treatment. Whether performing PBC or BAL affects clinically important outcomes requires further study.

Anti-Bacterial Agents↗
PubMed1999

Maternal intrapartum temperature elevation as a risk factor for cesarean delivery and assisted vaginal delivery.

OBJECTIVES: This study investigated the association of intrapartum temperature elevation with cesarean delivery and assisted vaginal delivery. METHODS: Participants were 1233 nulliparous women with singleton, term pregnancies in vertex presentations who had spontaneous labors and were afebrile (temperature: 99.5 degrees F [37.5 degrees C]) at admission for delivery. Rates of cesarean and assisted vaginal deliveries according to highest intrapartum temperature were examined by epidural status. RESULTS: Women with maximum intrapartum temperatures higher than 99.5 degrees F were 3 times as likely to experience cesarean (25.2% vs 7.2%) or assisted vaginal delivery (25.2% vs 8.5%). The association was present in epidural users and nonusers and persisted after birthweight, epidural use, and labor length had been controlled. In adjusted analyses, temperature elevation was associated with a doubling in the risk of cesarean delivery (odds ratio [OR] = 2.3, 95% confidence interval [CI] = 1.5, 3.4) and assisted vaginal delivery (OR = 2.1, 95% CI = 1.4, 3.1). CONCLUSIONS: Modest temperature elevation developing during labor was associated with higher rates of cesarean and assisted vaginal deliveries. More frequent temperature elevation among women with epidural analgesia may explain in part the higher rates of cesarean and assisted vaginal deliveries observed with epidural use.

Adult↗
PubMed1999

Comparison of the immunogenicity and safety of two 17D yellow fever vaccines.

As part of the clinical validation process of a new working seed of a licensed yellow fever vaccine (new working seed PV26, Stamaril; Pasteur Mérieux Connaught, Lyon, France), the immunogenicity and safety of two batches of this vaccine (PM-YF) were compared with those of another commercially available vaccine (Arilvax; Evans Medical-Wellcome, Liverpool, United Kingdom) in 211 healthy adults. While the geometric mean titer values at days 10-14 and day 28 after vaccination were higher in the PM-YF group, the vaccines provided equivalent seroprotection (titers > or = 1/10) one month after a single vaccine dose (100% PM-YF versus 99% W-YF; P = 0.001, by one-sided equivalence test). Both vaccines were safe. There were no serious local or systemic reactions reported, nor any clinically significant hepatic function abnormalities associated with the use of either vaccine. These two 17D yellow fever vaccines from different European vaccine manufacturers were highly immunogenic and safe, and provided equivalent seroprotection.

Adolescent↗
PubMed1999

Short report: treatment of snake envenomations by a new polyvalent antivenom composed of highly purified F(ab)2: results of a clinical trial in northern Cameroon.

A clinical trial was conducted in 2 health centers in northern Cameroon to assess the safety and efficacy of a new polyvalent antivenom composed of highly purified and pasteurized F(ab')2 (FAV-Africa). Forty-six patients with objective signs of envenomation, including 67% with hemorrhage, were included in the study. Each patient received at least 20 ml of FAV-Africa by direct, slow intravenous injection; 172 10-ml ampules were administered. All patients were clinically cured after treatment. Two patients (4.3%) showed minor immediate adverse events that may have been related to FAV-Africa (induration, light-headedness); no other treatment-related adverse event occurred. No patient had serum sickness. This trial confirms the safety of FAV-Africa administered by intravenous injection and its efficacy in the treatment of snake envenomations in sub-Saharan Africa.

Animals↗