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C Popp

Publications and source records attributed to C Popp.

16 recordsLinked to original sources

The organic cation transporters rOCT1 and hOCT2 are inhibited by cGMP.

The electrogenic cation transporters OCT1 and OCT2 in the basolateral membrane of renal proximal tubules mediate the first step during secretion of organic cations. Previously we demonstrated stimulation and change of selectivity for rat OCT1 (rOCT1) by protein kinase C. Here we investigated the effect of cGMP on cation transport by rOCT1 or human OCT2 (hOCT2) after expression in human embryonic kidney cells (HEK293) or oocytes of Xenopus laevis. In HEK293 cells, uptake was measured by microfluorimetry using the fluorescent cation 4-(4-(dimethyl-amino)styryl)-N-methylpyridinium iodide (ASP + ) as substrate, whereas uptake into Xenopus laevis oocytes was measured with radioactively labelled cations. In addition, ASP +-induced depolarizations of membrane voltages (Vm) were measured in HEK293 cells using the slow whole-cell patch-clamp method. Incubation of rOCT1-expressing HEK293 cells for 10 min with 100 mM 8-Br-cGMP reduced initial ASP + uptake by maximally 78% with an IC50 value of 24 +/- 16 mM. This effect was not abolished by the specific PKG inhibitor KT5823, indicating that a cGMP-dependent kinase is not involved. An inhibition of ASP + uptake by rOCT1 in HEK293 cells was also obtained when the cells were incubated for 10 min with 100 mM cGMP, whereas no effect was obtained when cGMP was given together with ASP +. ASP + (100 mM)-induced depolarizations of Vm were reduced in the presence of 8-Br-cGMP (100 mM) by 44 +/- 11% (n = 6). Since it could be demonstrated that [3H]cGMP is taken up by an endogeneous cyanine863-inhibitable transporter, the effect of cGMP is probably mediated from inside the cell. Uptake measurements with [14C]tetraethylammonium and [3H]2-methyl-4-phenylpyridinium in Xenopus laevis oocytes expressing rOCT1 performed in the absence and presence of 8-Br-cGMP showed that cGMP does not interact directly with the transporter. The data suggest that the inhibition mediated by cGMP observed in HEK293 cells occurs most likely via a mammalian cGMP-binding protein that interacts with OCT1-2 transporters.

Animals↗

Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1.

The rat organic cation transporter (rOCT)-2 was characterized by electrical and tracer flux measurements compared with rOCT1. By applying choline gradients to voltage-clamped Xenopus oocytes expressing rOCT2, potential-dependent currents could be induced in both directions. Tracer flux measurements with seven organic cations revealed similar Michaelis-Menten constant values for both transporters, with the exception of guanidine. In parallel experiments with rOCT2 and rOCT1, inhibition of tetraethylammonium transport by 12 cations, 2 weak bases, corticosterone, and the anions para-amminohippurate, alpha-ketoglutarate, and probenecid was characterized. The IC(50) values of many inhibitors were similar for both transporters, whereas others were significantly different. Mepiperphenidol and O-methylisoprenaline showed an approximately 70-fold lower and corticosterone a 38-fold higher affinity for rOCT2. With the use of these inhibitors together with previous information on cation transporters, experimental protocols are proposed to dissect out the individual contributions of rOCT2 and rOCT1 in intact proximal tubule preparations. Inhibition experiments at different pH levels strongly suggest that the weak base quinine passively permeates the plasma membrane at physiological pH and inhibits rOCT2 from the intracellular side.

Animals↗

Maitotoxin induces insertion of different ion channels into the Xenopus oocyte plasma membrane via Ca(2+)-stimulated exocytosis.

The activation of cation channels in oocytes of Xenopus laevis by the marine poison maitotoxin (MTX) was monitored as membrane current (I(m)), conductance (Gm) and membrane surface area determined by continuous measurements of membrane capacitance (Cm). When MTX (25 pM) was added to the bathing solution there was an abrupt, large increase in inward membrane currents. Current/voltage relationships (I/V curves) were linear and suggested activation of voltage-independent non-selective cation channels (NSCC). MTX-induced Ca(2+)-sensitive currents were mainly carried by Na+ and were suppressed by low (0 mM) or high (40 mM) external Ca2+ concentrations and removal of Na+. Gadolinium (Gd3+, 10-500 microM) also had inhibitory effects, demonstrating the possible involvement of stretch-activated cation channels (SACC). In a high concentration (500 microM), amiloride substantially reduced the MTX-activated current while lower amiloride concentrations (50-100 microM) stimulated the current further. Continuous measurements of Cm revealed that MTX induced exocytotic delivery and functional insertion of new channel proteins into the plasma membrane, indicated by a Ca(2+)-dependent increase in membrane surface area by around 28%. From these data we conclude that MTX activates NSCC that require relatively high concentrations of amiloride to be blocked. Furthermore, MTX possibly stimulates activation of Gd(3+)- and Ca(2+)-sensitive mechanosensitive cation channels. Stimulation of these channels is achieved by exocytotic delivery and functional insertion of new channels into the plasma membrane in a pathway that depends on the presence of extracellular Ca2+.

Amiloride↗

[Ion transport in nasal and paranasal sinus mucosa in mucoviscidosis and chronic sinusitis].

Cystic fibrosis (CF) is the most commonly inherited disease in Caucasians and is caused by a mutation in the gene encoding a membrane transport protein. This cystic fibrosis transmembrane conductance regulator (CFTR) is thought to be an apical Cl- channel activated by intracellular cAMP. Most recent findings suggest that CFTR is more than a pure Cl- channel and might be involved in the regulation of other transport systems. In the present study we show that CFTR as a Cl- channel plays only a minor role in primary cultured human nasal epithelium derived from non-CF and CF patients. These findings are especially of interest for non-CF human nasal epithelia in which CFTR is correctly inserted. In both tissues Cl- secretion is negligible as compared with Na+ absorption. We confirm and expand our previous observations that Na+ absorption in human nasal epithelium is the dominant ion transport process and that Cl- secretion is detectable in both CF and non-CF tissue. Moreover, we show that cAMP and ATP were not able to stimulate any silent Cl- channels in CF or non-CF human nasal epithelial cells. We further give evidence that in human nasal CF and non-CF epithelium Na+ absorption is mediated by epithelial Na+ channels (ENaC) that are either different from those of other epithelia or which exhibit altered regulation. These differences between Na+ channels of human nasal epithelium and "classical" epithelial Na+ channels include lack of activation by the intracellular second messenger cAMP and the steroid hormone aldosterone. We show further that human nasal Na+ channels are inhibited by Cl- channel blockers and exhibit a different pharmacology towards common Na+ channel blockers.

Chloride Channels↗

Chronic myelogenous leukemia in blast crisis: retrospective analysis of prognostic factors in 90 patients.

Ninety patients with Philadelphia chromosome-positive chronic myelogenous leukemia in blast crisis were reviewed to identify significant prognostic associations. At diagnosis of blast crisis the main clinical, laboratory, and cytogenetic data were recorded and evaluated for prognostic significance. At the time of the analysis 89 patients had died, with a median survival of 11 weeks from diagnosis of blast crisis. Patient characteristics demonstrated in the univariate analysis to have significant association with shorter survival were: thrombocythemia, leukocyte count above 20 x 10(9), Karnofsky index < 50%, nonlymphoid blast cell morphology, cytogenetic clonal evolution, the presence of a double Philadelphia chromosome or trisomy 8, and no response to therapy. In 17 of 59 patients (29%) evaluable for response to therapy a complete or partial remission was achieved. These responders had a significantly longer median survival (25 weeks) as compared with nonresponders (9 weeks). Response to therapy was significantly better in lymphoid blast crisis and in patients without clonal evolution. In a multivariate analysis containing all significant variables of the univariate analysis two parameters retained their prognostic significance: response to therapy and trisomy 8. In spite of the short overall survival in blast crisis, the determination of prognostic factors may be a useful tool for the clinician planning therapy, especially new therapeutic approaches.

Adult↗

Pretreatment of photoaged forearm skin with topical tretinoin accelerates healing of full-thickness wounds.

Pretreatment of skin with all-trans retinoic acid (tretinoin) has been shown to enhance wound healing. Previous studies have mainly used animal models to demonstrate this effect. We wanted to determine whether pretreatment could promote wound healing in severely photoaged dorsal forearm skin. Four elderly men with severely actinically damaged forearms were treated daily for 16 weeks. One arm was treated with 0.05-0.1% tretinoin cream (Retin A, Ortho), and the other with Purpose cream (Ortho) as a vehicle control. Four-millimetre punch biopsies were taken from both dorsal forearms prior to treatment. After 16 weeks, full-thickness 2-mm punch biopsies were taken from both sides. Serial photographs were taken, and healing of the wounds quantitatively assessed by image analysis. On the 11th day, the wounds were excised using a 4-mm biopsy punch. Biopsies were processed for light microscopy. After 16 weeks, the tretinoin-treated forearms showed moderate erythema and scaling. Polarized light photographs revealed multiple, red, vascularized foci and/or a diffuse network of small vessels. The histological effects were typical for tretinoin, i.e. compaction of the stratum corneum, epidermal acanthosis with correction of atypia, an increase in small vessels, and increased cellularity in the upper dermis. Purpose cream had no effect, either clinically or histologically. On the tretinoin-treated side, the wound areas were 35-37% smaller on days 1 and 4, and 47-50% smaller on days 6, 8, 11, compared with the controls. Clinically and histologically, reepithelialization occurred more rapidly. Thus tretinoin dramatically accelerated wound healing in photodamaged skin.

Administration, Cutaneous↗

Psoriasis vulgaris in 50 MHz B-scan ultrasound--characteristic features of stratum corneum, epidermis and dermis.

One hundred and forty fully developed, non-treated plaques of psoriasis vulgaris from the arms and legs of 22 patients were examined using 50 MHz B-scan ultrasound and compared with the images from adjacent, clinically normal skin. To visualize the dermis, high pre-amplification (digitization range 200 mV) was used, determined according to A-scan images. For evaluation of epidermal phenomena, low pre-amplification (digitization range 380 mV) was chosen in order to avoid overmodulation of the skin entry echo. In 10 patients, sonographic images were compared with histological sections from the exact same planes at the same magnification. At low pre-amplification, the skin entry echo is displayed as a markedly widened, frequently interrupted band composed of spots varying in thickness, height and echo density. Within these spots, several lamellae can be observed, represented as fine, echo-rich lines stacked one upon another. These phenomena correspond histologically to focal hyperparakeratosis, scaling and cracking of the stratum corneum. Due to the low amplification of the echo-signal the dermis is not visible. High pre-amplification allows evaluation of dermal changes. Below the entry echo there is an echopoor band (EPB) corresponding to the sum of acanthosis and infiltrate in the upper dermis. Underneath the EPB the dermis is represented as a zone with scattered internal echoes which are less intense than in normal skin. Dorsal shadows are typically present. They are artifacts emanating from epidermal regions with marked hyperkeratosis and disappear when the sonographic characteristics of the epidermis are changed, for instance by application of ointments prior to sonographic examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The hyperperfusion of the psoriatic plaque correlates histologically with dilatation of vessels.

We examined psoriatic lesions on the upper legs in 20 patients, using a two-dimensional Laser-Doppler-Scanner (Laser Doppler Perfusion Imager LDI, Lisca Development, Linköping/Sweden). The plaques were evaluated weekly during therapy with dithranol. Five plaques were reconstructed three-dimensionally before and after therapy (reconstruction program ANAT 3D, SIS, Münster, Germany). The psoriatic plaque was represented in the Laser Doppler Perfusion image as a sharply demarcated, hyperperfused area. The perfusion of the plaques dropped during therapy with dithranol to just slightly increased values, compared with normal skin (2.04 arbitrary units AU, healthy skin 1.1 AU). Using three-dimensional reconstruction, we investigated the volume of dermal vessels and the density of papillae. When compared, the volume of papillary vessels was twice as large in psoriatic as in healthy skin. The number of the papillae per square millimetre, detected by three-dimensional reconstruction, was not reduced significantly during therapy. We think that the increased perfusion of the psoriatic plaque is due to the combination of morphological (dilatation of vessels), dynamic (increased blood flow) and optical effects (reduced scattering and increased sampling depth of the laser-beam in acanthotic tissue).

Anthralin↗

[Considerations of the pathogenesis of parakeratosis variegata based on morphologic and molecular genetic findings].

We report on a 63-year-old woman who had been suffering from generalized parakeratosis variegata since she was 7 years old. Increased tightness of the skin was the only clinical symptom. On the whole integument except for the face, we found a fine network of hyper- and depigmentation and telangiectasias. The skin surface was dry and atrophic with fine lamellar scaling. Histological, immunohistological and ultrastructural findings indicated early infiltration by a cutaneous T-cell lymphoma. However, PCR analysis of the T-cell receptor gamma-chain genes revealed multiple amplification products favouring a polyclonal T-cell proliferation. In light of the clinical history over a period of 56 years, we consider parakeratosis variegata to be a benign, chronic inflammatory condition, as is confirmed by the results of PCR analysis in this patient.

Diagnosis, Differential↗

Converging evidence for identification of recurrent relationship themes: comparison of two methods.

The therapeutic process is complex, and researchers and clinicians alike search for organizing principles or underlying structures that will reduce this complexity and thereby augment the efficacy of their respective endeavors. As other papers in this issue indicate, one such organizing principle is the concept of a recurring relationship theme that can be identified in the patient's descriptions of current and past relationships, as well as observed in the patient's interaction with the therapist. This concept has its origins in Freud's discovery of the transference phenomenon (1912), wherein the patient reenacts early relationships with significant others in the relationship with the analyst, and in Sullivan's interpersonal theory of psychiatry, with its central tenet that "personality is the relatively enduring pattern of recurrent interpersonal situations which characterize a human life" (1953, pp. 110-11). In the psychoanalytic and interpersonal therapies, these recurrent interpersonal themes, associated with the patient's difficulty in living and characterized as self-defeating and self-perpetuating, can potentially serve three main purposes: diagnosing and describing patients' difficulties, focusing therapeutic interventions, and measuring change on an individual basis. However, until recently, research on transference and rigidity of interpersonal style has been hampered by the lack of objective and clinically relevant measures for quantifying this clinical phenomenon (Kiesler 1986; Luborsky and Spence 1978). Luborsky (1977) developed the first reliable method for operationalizing the transference concept. Since then, as the companion papers in this issue point out, several different methods have been developed (e.g., Gill and Hoffman 1982; Horowitz 1979; Schacht et al. 1984). Although these methods differ in the postulated structural composition or components of the transference theme or recurrent relationship theme, they operate from similar methods of assessment. This paper presents the results of an initial investigation into convergent validity (Cronbach and Meehl 1955) of two of the major relationship theme methods--the Core Conflictual Relationship Theme (CCRT) of Luborsky and colleagues (Luborsky 1977), and the Cyclical Maladaptive Pattern (CMP: formerly called the "dynamic focus") of the Vanderbilt group (Schacht et al. 1984; Schacht and Henry, in press). In our investigation, developers of the approaches independently applied their methods to the same interview with a depressed patient. It was hypothesized that aside from differences due to the structural composition, the two methods would identify a similar relationship theme.

Adult↗

An examination of three methods of psychodynamic formulation based on the same videotaped interview.

While psychodynamic theory and therapy are approaching their centennial, the science of psychodynamics is still in an earlier developmental stage. Any scientific field generates the most controversy and excitement when it is still developing. For psychodynamic psychology this means that its basic units of observation as well as its rules for justifying clinical inference in formulating and testing dynamic hypotheses require more development. In short, we are still evaluating different methods for both discovering and validating psychodynamic propositions. This is especially true for central features of dynamic psychology, including intrapsychic conflict, relationships, and transference patterns. This report compares three different methods for making a dynamic case formulation: 1) the Core Conflictual Relationship Theme (CCRT) of Luborsky (Crits-Christoph and Luborsky 1985a,b; Luborsky 1976, 1977, 1984, and companion paper in this issue; Levine and Luborsky 1981), 2) the Plan Diagnosis (PD) method of Silberschatz, Curtis and colleagues of the Mount Zion group (Caston 1986; Curtis and Silberschatz 1986; Rosenberg et al. 1986; Curtis et al. 1988) and, 3) the Idiographic Conflict Formulation (ICF) of Perry and Cooper (1985, 1986, and companion paper in this issue). Each has a slightly different focus. The CCRT focuses on relationship patterns as the central feature of individual dynamics and transference in or out of the treatment situation. The Plan Diagnosis focuses on dynamic features related to transference, resistance and insight in therapy. The Idiographic Conflict Formulation focuses on stress and internal conflict, and the individual's adaptation to them in or out of treatment.

Adjustment Disorders↗

Clinicians can agree in assessing relationship patterns in psychotherapy. The Core Conflictual Relationship Theme method.

This study examines interjudge agreement on formulations of dynamic themes in psychotherapy, using a session-based method, namely, the Core Conflictual Relationship Theme. Agreement was assessed by two methods: one was based on themes that were tailor-made for each case, while the other was based on coding themes into a standard set of categories. To assess agreement on the tailor-made formulations, a paired-comparisons procedure was used. For a sample of 35 patients, the similarity ratings for matched cases were significantly higher than for purposely mismatched cases. Using the standard set of categories, agreement was also good; weighted kappa values ranged from .61 to .70. The results also demonstrate reliability for the location of the relationship episodes, which form the database for the Core Conflictual Relationship Theme. Our positive results suggest that this guided clinical method can be used reliably as a measure of relationship patterns in psychotherapy; our results provide the first moderate-sized sample demonstration of clinicians' agreement in formulating this complex concept.

Attitude of Health Personnel↗

Idiopathic myelofibrosis: a retrospective study of 103 patients.

The clinical course of 103 patients (50 males, 53 females; median age 59 years) with idiopathic myelofibrosis (IMF) seen at our hospital between 1967 and 1986 was analyzed retrospectively. Common symptoms and signs at the time of diagnosis were: myelofibrosis (96%), splenomegaly (84%), anemia (81%), osteosclerosis (45%), malaise (41%) and leukocytosis (41%). It was possible to follow the majority of patients without treatment or with transfusion therapy only for prolonged periods of time. The use of cytostatic drugs and radiotherapy was restricted as much as possible. Probably due to this treatment strategy the incidence of acute leukemia was low (5%). Major thromboembolic complications were seen in 19% of the patients. Median survival of the patients was 4.3 years. The prognostic influence of several disease parameters determined at the time of diagnosis was tested: age, sex, leukocytes, platelets, hemoglobin, reticulocytes, LDH, ANP-score, spleen size and percentage of peripheral blood blasts + promyelocytes had no significant influence on the length of survival. Osteosclerosis, a presumed sign of advanced disease, was not correlated with survival either.

Adolescent↗