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R Walter

Publications and source records attributed to R Walter.

At least 73 records · Page 4Linked to original sources
PubMed1996

Effects of streptolysin O, polyriboinosinic-polyribocytidylic acid and combinations with cyclophosphamide on the hepatic arylamine N-acetyltransferase and cytochrome P450-dependent monooxygenases in rats.

There is evidence that immunostimulation depresses the function of various cytochrome P450 (CYP)-dependent monooxygenases but activates the arylamine N-acetyltransferase (NAT). Therefore, the effects of the synthetic immunostimulator polyriboinosinic-polyribocytidylic acid (plC, 8 mg/kg i.p.), of sublytic doses of the streptococcal toxin streptolysin O (SLO, 50 HU/kg i.v. for 5 d) and of the immunosuppressor cyclophosphamide (CP, 100 mg/kg i.p.) on NAT and some monooxygenases were studied in rat liver. It was also evaluated whether CP might antagonize the effects of plC and SLO on drug metabolism. SLO, plC and CP reduced CYP content and the activities of some monooxygenases. NAT was significantly inhibited by CP (given 5 d before sacrifice) but not by plC, SLO or CP when given 2 d before sacrifice. CP lacked any effect on NAT if it was administered prior to SLO. However, it deteriorated synergistically the inhibition of the monooxygenases caused by SLO and plC.

Animals↗
PubMed1995

Identification of several isoforms of T-kininogen expressed in the liver of aging rats.

We have previously shown that senescent Sprague-Dawley rats have significantly increased levels of kininogen (KG) mRNA and protein, when compared with younger counterparts. In the rat, five different isoforms of kininogen have been identified: high-molecular-weight K-kininogen, low-molecular-weight K-kininogen, and T1 alpha, T1 beta, and T2 kininogens. Several of these isoforms have been shown to differ in their biological properties. It was therefore considered relevant to establish which of these isoforms are expressed in the liver of old rats. To this end, we have isolated and sequenced nine independent cDNA clones from a library constructed using liver mRNA from healthy senescent rats. Predicted protein sequences indicate the presence of T-kininogens only. The relative lack of induction of K-kininogens during aging was further confirmed by RNA hybridization experiments. The nucleotide sequences reveal a microheterogeneity of silent polymorphisms, suggesting the presence and expression of several different alleles of the genes. From our data we conclude that (i) Several isoforms of T-KG are expressed in the liver of senescent Sprague-Dawley rats and (ii) T1 kininogens appear to be the most highly represented T-KG mRNA species in old rat livers.

Aging↗
PubMed1995

The use of mass spectrometry to examine the formation and hydrolysis of the phosphorylated form of phosphoglycerate mutase.

Electrospray mass spectrometry has been used to study the formation and hydrolysis of the phosphorylated forms of two phosphoglycerate mutases. The half-life of the enzyme from Saccharomyces cerevisiae was 35 min at 20 degrees C in 10 mM ammonium bicarbonate, pH 8.0. Addition of 1 mM 2-phosphoglycollate reduced this value by at least 100-fold. The phosphorylated form of the enzyme from Schizosaccharomyces pombe was much less stable with a half-life of less than 1 min. The results are discussed in terms of the kinetic properties of the enzymes. Mass spectrometry would appear to be a powerful method to study the formation and breakdown of phosphorylated proteins, processes which are of widespread significance in regulatory mechanisms.

Hydrolysis↗
PubMed1995

Stimulation of Na+/H+ exchange activity by endothelin in opossum kidney cells.

Endothelin-1 (ET-1) controls multiple aspects of kidney function. In this study we have analysed the effects of ET-1 on apical Na+/H+ exchange activity in opossum kidney (OK) cells. ET-1 (at 10(-10) M and 10(-8) M) activated Na+/H+ exchange activity within 5 min of exposure. ET-1 (10(-8) M) prevented PTH-induced (parathyroid hormone; 10(-8) M) inhibition of Na+/H+ exchange activity; it also abolished transport inhibition in response to 10(-3) M IBMX (isobutyl-methylxanthine) and 3 x 10(-7) M TPA (phorbol 12-myristate 13-acetate), but had no effect on the 8-bromo-cAMP-induced (10(-4) M) decrease of transport rate. Basal cAMP content, IBMX- and PTH-stimulated cAMP production were unaffected by ET-1 (10(-8) M). The stimulatory action of ET-1 (10(-8) M) on Na+/H+ exchange activity was prevented by calphostin C (10(-8) M). These data document that OK cells might serve as a useful in vitro model for analysis of cellular mechanisms involved in endothelin action; proteine kinase C activation seems to participate in the observed endothelin effects.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Nitric oxide and infection: another view.

Nitric oxide (NO) has been nicknamed "murderer" and "mediator" because it has toxic and signaling properties. We review these two aspects of NO synthesis from the perspective of the clinical infectious disease specialist by considering the potential of NO as an endothelium-derived relaxing factor (EDRF) in inflammation and sepsis and its potential as an antimicrobial system. We deviate from observations in recent authoritative reviews and point to important species differences that make it unlikely that NO serves as an EDRF mediating inflammatory vasodilatation in humans or that NO synthesized by humans phagocytes has an antimicrobial function. We propose that in humans, No synthesis is more confined and compartmentalized than in certain other animal species, and therefore, unwelcome toxicity, vasodilatation, or disturbance of paracrine signaling mechanisms (i.e., modulation of phagocytic cell functions) are avoidable during inflammation.

Animals↗
PubMed1995

Effects of streptolysin O, picibanil (OK 432) and interferon alpha 2A on cytochrome P-450-dependent monooxygenases and arylamine N-acetyltransferase in rat liver.

Streptolysin O, a thiol-activated exotoxin from group A beta-haemolytic streptococci, caused a dose-dependent depression of aniline hydroxylase, aminopyrine N-demethylase and ethylmorphine N-demethylase activities when added into the hepatic microsomal mixtures from male rats at concentrations 0.02-0.4 HU/mL in vitro. The activities of 7-ethoxycoumarin O-deethylase, 7-ethylresorufin O-deethylase and 7-pentylresorufin O-depentylase were not altered with the used concentrations of the toxin. Specific antibody against haemolytic action of streptolysin O added to incubation mixtures in vitro was not able to protect streptolysin-sensitive monooxygenases from the inhibition. The addition of streptolysin O (0.01-0.8 HU/mL) into the cytosol-containing medium did not significantly influence the activity of procainamide N-acetyltransferase. Immunomodulators picibanil (OK 432) and human recombinant interferon alpha 2A which are known to suppress oxidative metabolism in vivo in humans and animals, were without effect either on the cytochrome P-450-dependent monooxygenases or on the N-acetyltransferase activity when administered in vitro at the doses real in their clinical application (0.001-0.1 KE/mL of picibanil and 10-500 U/mL of alpha-interferon).

Animals↗
PubMed1995

Circadian-time rhythm of hepatic protein kinase C of rats pretreated with phenobarbital.

Circadian-time dependent differences of protein kinase C (PKC) activities as well as its susceptibility to a phenobarbital caused suppression in vivo (40 mg/kg b.i.d. for 3 days) were studied in outbred male Wistar rats weighing 280-360 g. The well-known phenobarbital induction of cytochrome P-450 and 7-pentylresorufin-O-depentylase (PROD) was associated with inhibition of the hepatic PKC. The activities of the cytosolic and membrane-bound PKC were significantly lower than in the respective controls. Statistically significant circadian-time differences were found. The activities of both cytosolic and membrane-bound PKC of control rats were highest in the evening (158% and 131%, respectively, of the morning values). Furthermore, phenobarbital inhibited the enzyme more strongly at 19.00 h than at 07.00 h. Our results suggest that increase of hepatic cytochrome P-450 content as well as induction of PROD are inversely related with the function of PKC.

Animals↗
PubMed1994

Tetrahydrobiopterin is a secretory product of murine vascular endothelial cells.

Tetrahydrobiopterin (BH4) is an obligatory cofactor of nitric oxide synthase and an essential regulator of its activity. The murine vascular endothelial cell line send1 constitutively secretes large amounts of BH4 as well as scant amounts of neopterin, an oxidized intermediate in the de novo biosynthesis of BH4. Further enhancement of BH4 and neopterin secretion is achieved by activation with endotoxin (LPS) and interferon-gamma. This finding is in accordance with previous described BH4 secretion by human endothelial cells. It supports the view that endothelial cells are the source of BH4 serving vascular needs in vivo. In septic conditions, BH4 released by endothelial cells in large amounts could serve induced nitric oxide synthase in smooth muscle cells, thereby acting as another endothelium-derived relaxing factor mediating vasodilatation.

Animals↗
PubMed1994

Differential regulation of constitutive and inducible nitric oxide production by inflammatory stimuli in murine endothelial cells.

The murine vascular endothelial cell line send1 expresses both constitutive and inducible nitric oxide (NO) synthases. Interferon-gamma (IFN gamma) or endotoxin (LPS) alone inhibited constitutive NO production in a dose and time dependent manner. Addition of L-arginine had no influence on the decrease of NO production caused by IFN gamma or LPS. On the other hand, IFN gamma and LPS synergized in the induction of high output NO production. Successive incubations with IFN gamma and LPS in different sequences revealed IFN gamma as the time setting signal for the induction of NO synthesis. These results demonstrate that LPS and IFN gamma have a direct suppressive effect on constitutive NO synthase while at the same time they strongly activate inducible NO production. Thus inflammatory stimuli trigger murine vascular endothelial cells to switch from constitutive to inducible NO synthase activity.

Animals↗
PubMed1994

Endogenous status of retinoids and their cytosolic binding proteins in limb buds of chick vs mouse embryos.

The morphogenetic role of all-trans-retinoic acid (RA) during limb development, especially its activity in directing anterior/posterior pattern formation remains controversial. We have measured retinoids and cytosolic binding proteins in anterior and posterior pieces of limb buds from comparably aged chick and mouse embryos expecting that localization patterns of morphological significance will be evident across species. Many species differences were found including: (1) nondetectable 3,4-didehydroretinoic acid (ddRA) in mouse limb buds, the predominant morphogenetically active retinoid in chick limbs; the precursor of ddRA, 3,4-didehydroretinol (ddROH), was also not present in mouse limb buds but found in high concentration in chick limb buds; (2) a higher concentration of morphogenetically active retinoid (RA + ddRA) in chick compared to mouse limb buds; (3) a high level of retinyl esters (1.5 microM) in chick limb bud, but undetectable concentration in mouse limb buds; and (4) a higher level of cytosolic retinoic acid binding proteins (CRABPs) in chick limb buds, especially CRABP II, which is 10X greater than in mouse limb buds. An interesting finding seen in mouse and chick limb buds was a disparity between the concentration of ligand and cytosolic binding protein. Retinol (ROH) and ddROH were present in much higher concentrations than cytosolic retinol binding protein (CRBP). Conversely, RA and ddRA were in far lower concentration than CRABPs. Any morphological significance of these disparities is unknown. A putative gradient of RA, high posteriorly, was found in chick limb buds as in earlier studies (Thaller and Eichele, 1987), but the magnitude of this gradient was less than previously reported. We also found ddRA in equal concentration in the anterior and posterior pieces of chick limb bud studied here, further weakening the idea of an RA gradient as the direct force in anterior/posterior pattern formation. The "free" concentration of retinoic acid, calculated from ligand and binding protein concentration and affinity, was slightly higher in posterior chick limb tissue (2.0X) and in mouse limb buds at a concentration similar to the Kd of murine nuclear retinoic acid receptors.

Animals↗
PubMed1994

[Ultrasound-guided fine-needle biopsy with an automatic full-incision system: the initial experiences and comparison with a conventional biopsy gun].

The purpose of this study was to evaluate the efficacy of a new automatic biopsy device (Autovac, Angiomed, Karlsruhe, Germany) in ultrasound (US) guided biopsies of focal abdominal lesions. 50 consecutive patients with focal abdominal lesions underwent US guided biopsies. In the first 24 patients, needle passes were performed with the Autovac system (outer diameter 0.95 mm) as well as with the Biopty gun (outer diameter 0.9 mm) (Bard Covington, USA). The size and the quality of the histologic and the cytologic material obtained by both systems were evaluated by histopathologists blinded to the system used. Autovac yielded significantly more material (defined as the area of the obtained tissue cores) and a significantly higher quality score than did the Biopty system. 96% of the histologic specimen and 100% of the cytologic smears obtained with Autovac were diagnostic, compared to 70 and 81% with Biopty, respectively. With the exception of a short-time elevation of the blood pressure in one patient, no complications occurred. The results indicate an advantage of the automatic full-cut type system Autovac over the tru-cut type Biopty gun in US-guided biopsies of focal abdominal lesions.

Abdomen↗
PubMed1994

[Reliability and validity of the German version of the Youth Self Report].

The aim of the present study was to investigate certain aspects of the reliability and validity of a German version of the Youth Self-Report (total behavior problem score) and to establish norms. In a sample of 252 patients from various child and adolescent psychiatric services and in an unselected sample of 1343 students from nearby schools high coefficients of internal consistency and split-half reliability (> 0.9) were obtained. An additional 105 students were tested and then retested after 5 weeks and again the rank correlations were high (boys: 0.86; girls: 0.90). The patients had higher total problem scores than the non-patients matched for age, sex, socioeconomic status, type of school and status as a foreigner. Patients with a diagnosis on axis 1 (psychiatric syndrome) or axis 5 (abnormal psychosocial situations) of the Multi-axial Classification Scheme were more maladjusted (higher total behavior problem score) than those without such a diagnosis. As expected, the score for the inpatients (N = 99) was higher than for the outpatients (N = 153). Because of the encouraging results, which justify further use of the Youth Self-Report, norms for the total behavior problem score (T-scores, percentiles) were calculated separately for the boys (N = 2085) and girls (N = 2119) from the general population (10-17 years of age).

Adolescent↗
PubMed1993

Casein kinase II copurifies with yeast DNA topoisomerase II and re-activates the dephosphorylated enzyme.

Mitotic division in yeast requires the activity of topoisomerase II, a DNA topology modifying enzyme that is able to disentangle sister chromatids after DNA replication. Previous work has shown that topoisomerase II is a phosphoprotein in intact yeast cells. We show here that when dephosphorylated in vitro, topoisomerase II is unable to cleave or decatenate kinetoplast DNA. An efficient kinase activity that modifies topoisomerase II on seven major sites was found to copurify with the enzyme purified from yeast. Characterization of this kinase, analysis of phosphotryptic peptides, and studies with a yeast mutant deficient in casein kinase II, indicate that the copurifying kinase is casein kinase II (CKII). Topoisomerase II itself has no self-phosphorylating activity. Modification of topoisomerase II by the copurifying kinase is sufficient to restore decatenation activity after dephosphorylation by alkaline phosphatase. The CKII target sites have been mapped to multiple serine and threonine residues on 4 tryptic fragments within the C-terminal 350 amino acids of yeast topoisomerase II. These results are consistent with a model in which the C-terminal domain of topoisomerase II is a negative regulatory domain that is neutralized by phosphorylation.

Amino Acid Sequence↗
PubMed1993

Social work leadership development through international exchange.

Social workers in large bureaucratic settings face the pressure to define their service in relation to other professional disciplines and to maintain a quality service despite conflicting mandates and economic restraints. Few strategies exist for providing training and education to senior social workers in order to help them develop leadership roles in multidisciplinary environments. This paper examines the characteristics and qualities necessary to provide social work leadership in a complex hospital environment. The ideas emerged from an international leadership exchange program with The Mount Sinai Medical Center in New York City. Aspects of this experience are used to illustrate leadership roles.

Academic Medical Centers↗
PubMed1992

Topoisomerase II: its functions and phosphorylation.

The gene encoding topoisomerase II in yeast is unique and essential, required for both mitotic and meiotic proliferation. The use of temperature-sensitive mutants in topoisomerase II have demonstrated roles in the relaxation of tortional stress, reduction of recombination rates, and in the separation of sister chromatids after replication. In vertebrate cells, topoisomerase II was shown to be the most abundant component of the metaphase chromosomal scaffold, and has been shown to play a role in chromosome condensation in vitro. The cell cycle control of chromosome condensation may well require phosphorylation of topoisomerase II, since the enzyme is more highly phosphorylated in metaphase than in G1. Recent studies have identified casein kinase II as the major enzyme phosphorylating topoisomerase II in intact yeast cells. The target sites of CKII are exclusively in the C-terminal 400 amino acids of topoisomerase II, the region that is most divergent among the eukaryotic type II enzymes and which is absent in the bacterial gyrase homologues.

Casein Kinase II↗