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C Pelz

Publications and source records attributed to C Pelz.

9 recordsLinked to original sources

Modeling random effects for censored data by a multivariate normal regression model.

A normal distribution regression model with a frailty-like factor to account for statistical dependence between the observed survival times is introduced. This model, as opposed to standard hazard-based frailty models, has survival times that, conditional on the shared random effect, have an accelerated failure time representation. The dependence properties of this model are discussed and maximum likelihood estimation of the model's parameters is considered. A number of examples are considered to illustrate the approach. The estimated degree of dependence is comparable to other models, but the present approach has the advantage that the interpretation of the random effect is simpler than in the frailty model.

Animals↗

IA in Kenyon cells of the mushroom body of honeybees resembles shaker currents: kinetics, modulation by K+, and simulation.

Cultured Kenyon cells from the mushroom body of the honeybee, Apis mellifera, show a voltage-gated, fast transient K+ current that is sensitive to 4-aminopyridine, an A current. The kinetic properties of this A current and its modulation by extracellular K+ ions were investigated in vitro with the whole cell patch-clamp technique. The A current was isolated from other voltage-gated currents either pharmacologically or with suitable voltage-clamp protocols. Hodgkin- and Huxley-style mathematical equations were used for the description of this current and for the simulation of action potentials in a Kenyon cell model. Activation and inactivation of the A current are fast and voltage dependent with time constants of 0.4 +/- 0.1 ms (means +/- SE) at +45 mV and 3.0 +/- 1.6 ms at +45 mV, respectively. The pronounced voltage dependence of the inactivation kinetics indicates that at least a part of this current of the honeybee Kenyon cells is a shaker-like current. Deactivation and recovery from inactivation also show voltage dependency. The time constant of deactivation has a value of 0.4 +/- 0.1 ms at -75 mV. Recovery from inactivation needs a double-exponential function to be fitted adequately; the resulting time constants are 18 +/- 3.1 ms for the fast and 745 +/- 107 ms for the slow process at -75 mV. Half-maximal activation of the A current occurs at -0.7 +/- 2.9 mV, and half-maximal inactivation occurs at -54.7 +/- 2.4 mV. An increase in the extracellular K+ concentration increases the conductance and accelerates the recovery from inactivation of the A current, affecting the slow but not the fast time constant. With respect to these modulations the current under investigation resembles some of the shaker-like currents. The data of the A current were incorporated into a reduced computational model of the voltage-gated currents of Kenyon cells. In addition, the model contained a delayed rectifier K+ current, a Na+ current, and a leakage current. The model is able to generate an action potential on current injection. The model predicts that the A current causes repolarization of the action potential but not a delay in the initiation of the action potential. It further predicts that the activation of the delayed rectifier K+ current is too slow to contribute markedly to repolarization during a single action potential. Because of its fast activation, the A current reduces the amplitude of the net depolarizing current and thus reduces the peak amplitude and the duration of the action potential.

Action Potentials↗

Successful unrelated marrow transplantation for patients over the age of 40 with chronic myelogenous leukemia.

Some older patients (> or =40 years) with chronic myelogenous leukemia (CML) who lack human leukocyte antigen (HLA)-identical sibling donors are not offered unrelated marrow transplantation because of concerns over excessive regimen-related toxicity, in particular due to graft-vs.-host disease (GVHD). The purpose of this study was to determine the efficacy and toxicity of unrelated marrow transplantation in older CML patients using a regimen designed to minimize the severity of GVHD. Thirty-one consecutive patients over the age of 40 with CML received unrelated marrow transplants between January 1988 and June 1997. Twenty-one patients were transplanted in chronic phase while ten were transplanted in the accelerated phase of their disease. Fifteen patients received transplants from phenotypically matched donors while 16 received marrow grafts from donors who were mismatched at one HLA locus. GVHD prophylaxis consisted of ex vivo T cell depletion of the donor marrow graft plus posttransplant cyclosporine administration. Durable engraftment was achieved in 29 of 31 patients (94%). The probability of developing grades II-IV or severe grades III-IV acute GVHD was 39.2 and 7.1%, respectively. There was no difference in the incidence of grades II-IV acute GVHD between patients transplanted with marrow grafts from phenotypically matched (38.1%) vs. those transplanted from mismatched unrelated donors (40%, p = 0.99). The 2-year probability of relapse for the entire population was 29.4%. Relapse was significantly higher for patients transplanted in accelerated phase (60%) than for those in chronic phase (13.8%, p = 0.027). The 2-year probability of overall survival and disease-free survival for the entire cohort was 56 and 45%, respectively. There was no significant difference in survival or disease-free survival for patients receiving phenotypically matched vs. mismatched marrow grafts. Immunological reconstitution for this cohort was compared with a younger (<40 years) patient population that had been similarly transplanted over the same time period. Immune function as assessed by total T cell, B cell, NK cell, and T cell subset reconstitution posttransplant was quantitatively equivalent in the two groups with most parameters normalizing within 18 months of transplant. We conclude that CML patients over the age of 40 who have either phenotypically matched or one antigen-mismatched unrelated donors can successfully undergo allogeneic marrow transplantation. T cell depletion of the marrow graft may be advantageous in these older patients by reducing GVHD severity, particularly in those patients transplanted with HLA-disparate marrow grafts.

Adult↗

Prognostic value of intraoperative blood flow measurements in vascular access surgery.

BACKGROUND: The purpose of this study was to correlate intraoperative blood flow measurements with outcome in vascular access surgery. METHODS: In 303 patients, 389 vascular access operations were performed. Intraoperative blood flow measurements were made immediately following construction of 227 autogenous and 162 prosthetic arteriovenous fistulas (AVFs) using a handheld flowprobe. Blood flow measurements were stratified by demographic variables such as age, race, sex, and presence of diabetes and were correlated with primary and secondary (assisted) patency. Statistical methods included life-table analysis and Cox proportional hazards model. RESULTS: Blood flow increased progressively from distal to proximal access sites and was not significantly affected by age, race, sex, or presence of diabetes. Autogenous AVFs with flow rates at or below 320 mL/min and polytetrafluoroethylene (PTFE) grafts with flow rates at or below 400 mL/min had significantly worse primary and secondary patency rates compared to their higher flow counterparts at all sites. Using hazard analysis flow rate was the single most important determinant of primary and secondary patency. PTFE grafts with flow rates at or below 400 mL/min also required more interventions (1.58 per patient-year) and failed sooner (median time, 0.5 +/- 4.7 months) than grafts with flow rates above 400 mL/min (1.08 interventions per patient-year; P = .03; median time, 1.6 +/- 5.0 months; P = .003). CONCLUSIONS: Intraoperative measurements of access blood flow provide objective, reliable data that correlate with outcome. Routine use of this technology might lead to more efficient management of patients undergoing hemodialysis access surgery.

Adult↗

Odorant intensity as a determinant for olfactory conditioning in honeybees: roles in discrimination, overshadowing and memory consolidation.

Stimulus intensity is an important determinant for perception, learning and behaviour. We studied the effects of odorant concentration on classical conditioning involving odorants and odorant-mechanosensory compounds using the proboscis-extension reflex in the honeybee. Our results show that high concentrations of odorant (a) support better discrimination in a feature-positive task using rewarded odorant-mechanosensory compounds versus unrewarded mechanosensory stimuli, (b) have a stronger capacity to overshadow learning of a simultaneously trained mechanosensory stimulus, and (c) induce better memory consolidation. Furthermore, honeybees were trained discriminatively to two different concentrations of one odorant. Honeybees are not able to solve this task when presented with rewarded low versus unrewarded high concentrations. Taken together, our results suggest that high concentrations of odorant support stronger associations (are more 'salient') than low concentrations. Our results, however, do not indicate that honeybees can treat two different concentrations of one odorant as qualitatively different stimuli. These findings fill a gap in what is known about honeybee olfactory learning and are a first step in relating behaviour to recent advances in the physiological analysis of coding for odorant concentration in honeybees.

Animals↗

Characterization of the membrane-associated GTPase activity: effects of chemotactic factors and toxins.

Membranes prepared from rabbit neutrophils exhibit GTPase activity which can be stimulated by the chemotactic factor fMet-Leu-Phe. The maximum contribution of the ATPase activities to the basal and the fMet-Leu-Phe-stimulated GTPase activities are less than 20% and 9%, respectively. The basal GTPase activity has a Vmax = 34.2 +/- 1.3 (pmol/mg protein, min) and a Km = 0.39 +/- 0.03 microM; and the fMet-Leu-Phe-stimulated has a Vmax = 52.3 +/- 2.5 (pmol/mg protein, min), and a Km = 0.29 +/- 0.02 microM. The GTPase activity can be stimulated by fMet-Leu-Phe and leukotriene B4. Unlike these two chemotactic factors, concanavalin A does not stimulate this GTPase activity. In addition, the rise in intracellular concentration of free calcium produced by concanavalin A is not inhibited by pertussis toxin treatment. Both the basal and stimulated GTPase activities are affected by pertussis toxin, cholera toxin and N-ethylmaleimide.

Animals↗

Treatment of rabbit neutrophils with phorbol esters results in increased ADP-ribosylation catalyzed by pertussis toxin and inhibition of the GTPase stimulated by fMet-Leu-Phe.

The effects of pretreatment of rabbit neutrophils with phorbol 12-myristate 13-acetate on the ability of pertussis toxin to catalyze ADP-ribosylation and of fMet-Leu-Phe to activate a high-affinity GTPase in these cell homogenates were examined. The addition of phorbol 12-myristate 13-acetate, but not 4 alpha-phorbol 12,13-didecanoate, to intact cells was found to stimulate by more than 100% the pertussis toxin-dependent ribosylation of a 41 kDa protein (either the alpha-subunit of the 'inhibitory' guanine nucleotide-binding protein N or a closely analogous protein) and to inhibit by more than 60% the activation by fMet-Leu-Phe of the GTPase of the neutrophil homogenates. The addition of fMet-Leu-Phe to intact cells increases the ADP-ribosylation catalyzed by pertussis toxin of the 41 kDa protein. On the other hand, the exposure of neutrophil homogenates to fMet-Leu-Phe results in a decreased level of ADP-ribosylation. This decreased ribosylation reflects a dissociation of the GTP-binding protein oligomer that is not followed by association, possibly because of the release of the alpha-subunit into the suspending media. The implications of these results for the understanding of the mechanism of inhibition of cell responsiveness by phorbol esters and the heterologous desensitization phenomenon are discussed. Prominent among these are the possibilities that (i) the rate of dissociation of the Ni oligomer is affected by the degree of its phosphorylation by protein kinase C, and/or (ii) the dissociated phosphorylated alpha-subunit (the 41 kDa protein) is functionally less active than its dephosphorylated couterpart.

Adenosine Diphosphate Ribose↗

[Transanal endoscopic surgery of the rectum - testing a new method in animal experiments].

Surgery of the lower third of the rectum can be done without difficulty through the anus using an endoscopical approach. Polyps or tumors located in the upper two thirds of the rectum can be removed using the Mason or Kraske procedure, or by the transabdominal approach. A new endoscopic technique has been developed with the aim, to allow surgery in the whole rectum through the anus. The rectum is being dilated by mechanical means and air insufflation. An oblique angle stereoscopic endoscope as well as modified surgical instruments are used. In animals 47 excisions of mucosa were done, and the incisions were closed by continuous suture. Application of this technique in a clinical setting is planned.

Anal Canal↗