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Biomedical subjects

K Scholz

Publications and source records attributed to K Scholz.

At least 19 recordsLinked to original sources

A case of cerebral Whipple's disease initially presenting with isolated focal myoclonus.

Neurological manifestations in Whipple's disease are highly variable and tend to occur at later stages of the disease. However, isolated, focal neurological symptoms are reported to be rare. Here we describe the successful treatment of a case of cerebral Whipple's disease initially presenting solely with isolated myoclonic jerks of the left hand and forearm evolving to a segmental myoclonus at a later stage. Additionally, we present - to our knowledge - a novel treatment by administration of immunomodulatory therapy (IVIg) in addition to established antibiotics.

Adult↗

Efficacy of balloon valvuloplasty in patients with critical aortic stenosis and cardiogenic shock--the role of shock duration.

BACKGROUND: Because of limited long-term success, aortic balloon valvuloplasty is considered to be a palliative procedure, including patients at excessive risk for standard therapy-aortic valve replacement-that is, those in cardiogenic shock. HYPOTHESIS: The study was undertaken to evaluate the outcome of balloon valvuloplasty for critical aortic stenosis complicated by cardiogenic shock. METHODS: Over a 10-year-period, we followed 14 patients (age 74+/-11 years, range 50-91) presenting in cardiogenic shock and critical aortic stenosis, who underwent valvuloplasty, together with 19 patients with critical aortic stenosis requiring urgent major noncardiac surgery. RESULTS: In patients in shock, calculated aortic valve area could be increased successfully by at least 0.3 cm2, from 0.38+/-0.09 to 0.81+/-0.12 cm2, with an insignificant increase in cardiac index from 1.89+/-0.33 to 2.01+/-0.41 l/min * m2. In-hospital mortality was 71% (10 patients). Two patients underwent valve replacement within 16 days and survived after 1 year, as did two patients refusing surgery. By multivariate logistic regression analysis, only an interval between onset of shock symptoms and valvuloplasty of > 48 h was significantly associated with fatal outcome (p < 0.01). In those patients requiring noncardiac surgery, this was possible after valvuloplasty in 95% who survived 1 year after hospital discharge. One patient in this group died of pulmonary embolism the day after the procedure. CONCLUSION: These data support the concept of causal treatment in patients with cardiogenic shock, as well as in the setting of cardiogenic shock and critical aortic stenosis, at the earliest possible convenience.

Aged↗

c-MYB oncogene-like genes encoding three MYB repeats occur in all major plant lineages.

Since the identification of the first plant MYB-like protein, the Zea mays factor C1, the number of MYB-related genes described has greatly increased. All of the more than 150 plant MYB-like proteins known so far contain either two or only one sequence-related helix-turn-helix motif in their DNA-binding domain. Animal c-MYB genes contain three such helix-turn-helix motif-encoding repeats (R1R2R3 class genes). It has therefore been concluded that R2R3-MYB genes are the plant equivalents of c-MYB and that there are significant differences in the basic structure of MYB genes of plants and animals. Here, we describe expressed R1R2R3-MYB genes from Physcomitrella patients++ and Arabidopsis thaliana, designated PpMYB3R-1 and AtMYB3R-1. The amino acid sequences of their DNA-binding domains show high similarity to those of animal MYB factors, and less similarity to R2R3-MYB proteins from plants. In addition, R1R2R3-MYB genes were identified in different plant evolutionary lineages including mosses, ferns and monocots. Our data show that a DNA-binding domain consisting of three MYB repeats existed before the divergence of the animal and plant lineages. R1R2R3-MYB genes may have a conserved function in eukaryotes, and R2R3-MYB genes may predominantly regulate plant-specific processes which evolved during plant speciation.

Amino Acid Sequence↗

Modulation of cytokine-induced expression of secretory phospholipase A2-type IIA by protein kinase C in rat renal mesangial cells.

Renal mesangial cells express the 14 kDa secretory phospholipase A2-type IIA (sPLA2-IIA) in response to interleukin-1beta (IL-1beta). In order to understand the regulation of cytokine-induced sPLA2-IIA induction in more detail, we investigated whether phorbol ester-activated protein kinase C (PKC) has an influence on the IL-1beta-induced expression of sPLA2-IIA. We found that treatment of mesangial cells with the biologically active phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate inhibited IL-1beta induction of sPLA2-IIA mRNA, protein, and activity, whereas the inactive compound 4alpha-phorbol 12,13-didecanoate was without effect. An 8-hr pretreatment with PMA, which led to down-regulation of PKC-alpha and -delta isoenzymes, still inhibited sPLA2-IIA induction. Only after down-regulation of PKC-epsilon isoenzyme by 24-hr preincubation with PMA were we able to reconstitute the IL-1beta-induced sPLA2-IIA expression. Thrombin as a physiological activator of PKC in mesangial cells exerted similar effects as PMA and inhibited sPLA2-IIA expression. The selective PKC inhibitor calphostin C potentiated IL-1beta induction of sPLA2-IIA mRNA levels and partially reconstituted the thrombin-induced inhibition of sPLA2-IIA mRNA and activity. These data show that IL-1beta induction of sPLA2-IIA can be modulated by PKC and that the epsilon-isoenzyme of the PKC family is the most likely candidate mediating the suppression of cytokine-induced sPLA2-IIA expression in mesangial cells.

Animals↗

Cross-talk between group IIA-phospholipase A2 and inducible NO-synthase in rat renal mesangial cells.

Features of glomerulonephritis are expression of the inducible form of NO synthase (iNOS) as well as expression of the secretory group IIA-phospholipase A2 (sPLA2) in mesangial cells. Interleukin 1beta (IL-1beta) induces both enzymes with a similar time course resulting in an increase in nitrite production and sPLA2-IIA activity. In this study we investigated the relationship between the formation of NO and sPLA2-IIA induction in rat renal mesangial cells. Incubation of mesangial cells with the NO-donor, spermine-NONOate, for 24 h induced sPLA2-IIA mRNA expression and activity, whereas S-nitroso glutathione alone had only a small stimulatory effect. Stimulation of cells with IL-1beta caused a marked increase in sPLA2-IIA mRNA and activity that were potentiated 3 fold by both NO donors. Coincubation of cells with IL-1beta and the NOS inhibitor, L-N(G) monomethylarginine (L-NMMA), caused a dose-dependent inhibition of cytokine-induced sPLA2-IIA mRNA expression and activity. sPLA2-IIA activity was not stimulated by 8-bromo-cyclic GMP indicating that NO-induced sPLA2-IIA induction is independent of cyclic GMP-mediated signal transduction. These data show that NO contributes to the expression by cytokines of sPLA2-IIA and establishes a novel type of interaction between iNOS and sPLA2-IIA in mesangial cells. This cross-talk between inflammatory mediators may help to promote and sustain an inflammatory state in the kidney.

8-Bromo Cyclic Adenosine Monophosphate↗

Self-care guidelines: finding a common ground.

Pressure to reduce overall transplant costs is one of the factors which has led to earlier hospital discharge and increased patient management challenges in outpatient and home care settings. Earlier discharge often contributes to decreased opportunity to provide and ensure comprehension of critical patient and family education, resulting in challenges for home care clinicians who are committed not only to patient and environmental assessments, but to helping assure patient and family understanding of and compliance with critical posttransplant responsibilities and regimens. This article describes a transplant patient education tool that was developed for use with all types of solid organ transplant recipients discharged from multiple centers yet managed by a single home care organization. The tool provides patient education information that can be realistically reviewed and reinforced during the home visit. The resource focuses on key self-care issues to promote wellness and graft survival and help prevent adverse outcomes.

Home Care Services↗

Negative regulation of interleukin-1beta-activated neutral sphingomyelinase by protein kinase C in rat mesangial cells.

Endogenous ceramide is produced by the action of acidic or neutral sphingomyelinases (SMase) in response to stimuli such as proinflammatory cytokines or other inducers of stress. Interleukin-1beta (IL-1beta) is known to stimulate ceramide formation in rat renal mesangial cells; however, the respective subtype of SMase and its regulation have not been investigated. We found that IL-1beta induced an increase in endogenous ceramide levels via the action of a neutral SMase but not an acidic SMase in rat mesangial cells. Cytokine-induced activation of neutral SMase was inhibited by stimulation of protein kinase C (PKC) by the phorbol ester TPA which caused a reduction of ceramide back to control levels. This inhibitory effect of TPA was reversed by the specific PKC-inhibitor Ro-318220. Long-term incubation (24 h) of mesangial cells with TPA, which downregulates PKC-alpha, -delta, and -epsilon isoenzymes, resulted in a recovery of IL-1beta-stimulated neutral SMase activity as well as ceramide formation. These data implicate an important modulatory function of PKC in ceramide production in IL-1beta-activated mesangial cells.

Animals↗

Localization of prostaglandin-H synthase-1 and -2 in mouse skin: implications for cutaneous function.

Prostaglandin-H synthase (PGHS)-1 and -2 expression in mouse skin and in keratinocytes in culture was determined using immunohistochemistry and Western blot analysis. In normal skin PGHS-1 immunoreactivity was found in individual keratinocytes present in the interfollicular epidermis and the upper part of the hair follicle. PGHS-2 immunostaining was detected in very few individual basal cells of the interfollicular epidermis and of the hair follicle. Upon induction by TPA of an inflammatory epidermal hyperplasia (regenerative hyperplasia) the number of PGHS-2-expressing keratinocytes scattered throughout the basal but not the suprabasal compartment of the interfollicular epidermis was found to be increased while PGHS-1 expression remained unchanged. PGHS-2 immunoreactivity in paraffin sections from TPA-treated skin showed a nuclear in some and a perinuclear and cytoplasmic localization in other keratinocytes. This different distribution may correlate with the proliferative state, since immunofluorescence analysis of mouse keratinocytes in culture demonstrated a predominant perinuclear and cytoplasmic PGHS-2 localization in cycling keratinocytes but a prevalent staining of the nucleus and the nuclear membrane in noncycling cells. Stimulation of proliferation of murine primary keratinocytes by serum resulted in an increased PGHS-2 expression, whereas induction of terminal differentiation by Ca2+ caused a down-regulation of PGHS-2 protein. Only minor changes in PGHS-1 expression were seen. Our data suggest that expression of PGHS-2 in mouse skin epidermis is related to epithelial regeneration.

Animals↗

Cost-effectiveness in diagnostic radiology: how can contrast media manufacturers contribute?

In recent years, awareness of the limitations of health care resources has increased within pharmaceutical companies. Indeed, it is believed that if cost-effectiveness in radiology in not improved, patients will suffer from limited access to the latest and best technologies. In addition, we must all shoulder part of the responsibility to close the gap between the diagnostic opportunities for patients in highly industrialized countries and those in countries under more difficult economic conditions by offering achievable diagnostic solutions. To achieve these goals, we must first realize that the long-term effect of necessary short-term cost containment will be limited if focus on and investment in better education, information systems, and innovation are not maintained. Second, for any new contrast medium, improvement in diagnostic efficacy and quality must be demonstrated. The third step is based on an editorial statement by Hillman [5] in a recent issue of Radiology. He wrote that health insurance data bases are often too coarse to be really meaningful for evaluations of the cost of imaging and that validation of the value of diagnostic imaging requires that researchers show benefits related to improvements in quality of life. Manufacturers of contrast media could support future research approaches with this objective. Experience in the industry shows that the best long-term measure for reducing costs is to focus on investment in improved effectiveness through innovation.

Contrast Media↗

Differential expression of prostaglandin-H synthase isoenzymes in normal and activated keratinocytes in vivo and in vitro.

Normal mouse epidermis constitutively expresses prostaglandin-H synthase 1 (PGHS-1) but no PGHS-2. Acute inflammation and epidermal hyperplasia, (hyperplastic transformation), as evoked in adult mouse skin in vivo by wounding or by the phorbol ester phorbol 12-myristate 13-acetate (PMA), resulted in a transient induction of PGHS-2 expression while PGHS-1 remained unchanged. Under conditions of a stationary epidermal hyperplasia, as in neonatal mouse epidermis, PGHS-1, but not PGHS-2, expression was observed. Induction of 'balanced hyperproliferation' by 4-O-methyl-phorbol 12-myristate 13-acetate (4-O-methyl-PMA) did not lead to PGHS-2 expression. When keratinocytes were isolated from neonatal mouse skin and separated by Percoll density-gradient centrifugation according to their stage of differentiation, PGHS-1 mRNA expression and protein were found to be highest in the differentiated cells compared with those from the proliferative compartment. A similar distribution of PGHS-1 mRNA was found in keratinocytes from adult mice, whereas PGHS-1 protein was equally distributed in all cell types. Contrary to the situation in intact epidermis, PGHS-2 mRNA but no protein was detected in all cell fractions. Established keratinocyte lines constitutively expressed both isoenzymes at different ratios. In the mouse line MSCP5 an almost exclusive expression of PGHS-2 was found, which was further enhanced by PMA treatment. These data indicate that the expression of PGHS-2 in mouse epidermis is specifically related to the emergency reaction of hyperplastic transformation.

Animals↗

Differential expression of prostaglandin H synthase isozymes during multistage carcinogenesis in mouse epidermis.

An anti-tumor-promoting effect of indomethacin and related nonsteroidal anti-inflammatory drugs (NSAIDs) as well as the ability of the tumor promoter 12-O-tetradecanoylphorbol-13- acetate (TPA) to increase the level of prostaglandins in murine keratinocytes and mouse epidermis in vivo has been repeatedly documented. Here, the expression of prostaglandin H synthase (PGHS) isozymes, which are major targets of NSAIDs, was investigated in different stages of tumor development in mouse skin. Mouse epidermis in vivo constitutively expressed PGHS-1. PGHS-1 steady-state levels remained unchanged upon induction of acute or chronic epidermal hyperplasia by TPA and in papillomas and carcinomas generated by the initiation-promotion procedure, with 7,12-dimethylbenz[a]anthracene as initiator and TPA as promoter. Thus, the elevated prostaglandin level in the acute hyperplastic epidermis was very likely due to PGHS-2 induction. Repeated applications of TPA resulted in stationary hyperplasia and downregulation of PGHS-2 expression and prostaglandin levels, suggesting that the epidermis had adapted to the TPA stimulus. In papillomas and carcinomas, however, constitutive overexpression of PGHS-2 was found, with a large amount of prostaglandin E2 and prostaglandin F2 alpha. Keratinocyte cell lines corresponding to different stages of tumor development also constitutively over-expressed PGHS-2. Considered with inhibitor studies, these data suggest that PGHS-2 has a critical role in skin carcinogenesis. The anti-tumor-promoting effect of the PGHS inhibitor indomethacin is specifically reversed by prostaglandin F2 alpha, indicating that this prostaglandin type has a significant role in tumor development.

Amino Acid Sequence↗

Measurements of spin-lattice relaxation times, T1, in Na2O-MgO-SiO2 glasses doped with MnO.

Silicate glasses without paramagnetic components show 29Si relaxation times, T1, in the order of minutes. Because of these T1 values, unacceptably long instrument times are needed to obtain satisfactory' signal-to-noise ratios. Therefore, all samples were doped with MnO when microstructures of electrode glasses were investigated. Small amounts of paramagnetic ions in the glass reduce the relaxation time but do not affect the electrode properties. In any case when the distribution of manganese ions is homogeneous, the relaxation rates are proportional to the MnO content. The spin-lattice relaxation times of the different Qn species are similar within error limits. The best spectra were obtained using 0.1 mol% MnO.

Electrodes↗