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R Metzger

Publications and source records attributed to R Metzger.

At least 73 records · Page 4Linked to original sources
PubMed1997

[Quality assurance in inpatient treatment of depression. Aspects of quality monitoring and external quality assurance exemplified by a pilot project of inpatient treatment of depression].

Aspects of a Pilot Study on Depression Treatment According to Quality Monitoring and External Quality Assurance: Experiences and results of a pilot study on quality of the treatment of depressed inpatients in 4 different psychiatric hospitals (2 state mental hospitals, 1 university clinic, 1 psychiatric clinic at a city general hospital) according to so-called process and outcome quality, are reported. Outcome data (self-ratings, observer rating, clinical global impression admission versus discharge, patient satisfaction with treatment, duration of inpatient stay/and patient data are reported while comparing the 4 hospitals. Difficulties and problems of data collection, assessments and comparison of 4 different hospitals are discussed.

Adult↗
PubMed1996

Molecular cloning and functional characterization of a mouse bradykinin B1 receptor gene.

The gene encoding a putative mouse bradykinin B1 receptor was cloned from a genomic library by low stringency screening. Analysis of two isolated clones revealed a region which contains an open reading frame uninterrupted by introns and encodes a 334 amino acid protein, which exhibits seven potential transmembrane domains and is 68% identical to the human and rabbit bradykinin B1 receptors. Lipopolysaccharide-treatment induces B1 receptor transcripts in the heart, liver, and lung. Stable expression of the coding region in COS-7 cells resulted in high levels of binding sites for the specific B1 ligand des-ARG10 kallidin (Kd = 1.3 nM; Bmax = 51 fmol/mg protein). The rank order of affinity of the receptor for the agonists and antagonists was: des-Arg9BKdes-Arg9Leu8BKdes- Arg10kallidin >> Hoe-140=bradykinin. Functional coupling of the cloned receptor was demonstrated by the dose-dependent effects of des-Arg(9)BK on the extracellular acidification rate in stably transfected COS-7 cells. This effect was not produced by bradykinin and could be blocked by the B1 antagonist des-Arg9Leu8BK.

Amino Acid Sequence↗
PubMed1995

Expression of the mouse and rat mas proto-oncogene in the brain and peripheral tissues.

We isolated the mas proto-oncogene from a mouse genomic library. Sequence analysis showed that it contains an open reading frame without intervening sequences. The amino acid sequence deduced confirms the seven-transmembrane-domain structure and exhibits 97% and 91% amino acid homology with the rat and the human Mas, respectively. In mice and rats, mas mRNA was detected in the testis, kidney, heart, and in the brain regions: hippocampus, forebrain, piriform cortex, and olfactory bulb. Testicular mas mRNA from rats increases markedly during development, while cerebellar mRNA is high postnatally but completely disappears at later stages. We conclude that the product of the mouse mas gene may be involved in the development of the brain and testis.

Amino Acid Sequence↗
PubMed1995

The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells.

Angiotensin II (ANG II) is known to be a potent growth promoting factor for vascular smooth muscle cells and fibroblasts but little is known about its influence on growth in endothelial cells. We studied the effects of ANG II on endothelial growth and the role of the angiotensin receptor subtypes involved. Proliferation of rat coronary endothelial cells (CEC) and rat vascular smooth muscle cells (VSMC) was determined by [3H]thymidine incorporation, the MTT-test and by directly counting cells in a coulter counter. Angiotensin AT1- and AT2-receptors were demonstrated by binding studies and by the presence of their respective mRNA through reverse transcription polymerase chain reaction (RT-PCR). In contrast to VSMC, which in culture only express the AT1-receptor, CEC express both, AT1- and AT2-receptors simultaneously up to the third passage. Whereas ANG II stimulated growth of quiescent VSMC, an effect abolished by pretreatment with the AT1-receptor antagonist, losartan, ANG II did not induce proliferation in quiescent CEC. However, after pretreatment of quiescent endothelial cells (< passage 4) with the AT2-receptor antagonist, PD 123177, ANG II induced proliferation. This effect was reversed by additional pretreatment with losartan. ANG II significantly inhibited the proliferation of bFGF-stimulated CEC in a dose-dependent manner by maximally 50%. This effect was prevented by PD 123177 while losartan was ineffective. The AT2-receptor agonist, CGP 42112, mimicked the antiproliferative actions of ANG II, confirming the specificity of the effect. Our results show that the growth modulating actions of ANG II depend on the type of angiotensin receptor present on a given cell. In coronary endothelial cells, the antiproliferative actions of the AT2-receptor offset the growth promoting effects mediated by the AT1-receptor.

Angiotensin I↗
PubMed1995

Environmental health and Hispanic children.

There are numerous indicators that Hispanics face a disproportionate risk of exposure to environmental hazards. Ambient air pollution, worker exposure to chemicals, indoor air pollution, and drinking water quality are among the top four threats to human health and are all areas in which indicators point to elevated risk for Hispanic populations. These data, juxtaposed with data on the health status of Hispanics, tell us that the environmental health status of Hispanics and their children is poor. At the same time, significant inadequacies in the collection of data on Hispanics make it difficult to make improving Hispanic environmental health status a priority. These inadequacies include the failure to use Hispanic identifiers in data collection and failure to collect sample sizes large enough to allow for breakouts of data by Hispanic subgroup. In addressing environmental justice issues, the U. S. Environmental Protection Agency (U.S. EPA) and the Department of Health and Human Services (DHHS) should prioritize improving the quantifiability of environmental exposures and risk based on race or ethnicity. However, improving data should not be the prerequisite to significant, affirmative steps by DHHS and U.S. EPA to address environmental and environmental health problems facing Hispanic communities. In particular, a health-based approach to environmental justice should be the priority.

Air Pollution↗
PubMed1995

Converting enzyme inhibitors differentially affect expression of genes of the renin-angiotensin system.

There is considerable evidence from clinical and experimental studies that blood pressure is lowered by converting enzyme inhibitors (CEIs) irrespective of whether the plasma renin-angiotensin system (RAS) is stimulated. New insights into the molecular biology of the RAS--in particular, the gene expression of renin and angiotensinogen in various tissues--support the view that the antihypertensive properties of CEIs may be mediated, at least in part, by interaction with tissue RAS. To investigate this possibility further, stroke-prone spontaneously hypertensive male rats (SHRSP) were treated orally for 28 days with different CEIs or a peripheral vasodilator to study the effects of the various drug treatments on the gene expression of the RAS in selected tissues. Different effects of different CEIs on tissue gene expression suggest localized action and some degree of organ specificity of the drugs. The experiments involved: (1) untreated controls; and rats treated with either (2) 50 mg/kg of captopril; (3) 10 mg/kg of lisinopril; (4) 10 mg/kg of cilazapril; (5) or 30 mg/kg of the vasodilator hydralazine with 10 rats/group. All of the study drugs reduced systolic blood pressure to normotension. Cardiac hypertrophy and the heart:body weight ratio were significantly decreased only in the CEI-treated animals, and kidney renin mRNA was increased by the CEIs whereas hydralazine had no effect on heart weight or kidney renin mRNA. Plasma renin activity increased in parallel with kidney renin mRNA levels. Liquid hybridization and Northern blotting assays revealed drug-specific regulation of the angiotensinogen mRNA level in the adrenal gland, with cilazapril producing the most marked stimulation of adrenal angiotensinogen gene expression. Both lisinopril and cilazapril suppressed hypothalamic angiotensinogen mRNA. There were no significant changes in angiotensinogen gene expression observed in the kidney or liver with any of the CEIs. In conclusion, these data show that CEIs interact differentially and drug-specifically with tissue RAS, and have class-specific effects on cardiac hypertrophy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

On the plasticity of the cerebellar renin-angiotensin system: localization of components and effects of mechanical perturbation.

This study focuses on the renin-angiotensin system (RAS) in the cerebellar cortex and changes within this system after mechanically induced cerebellar injury. Using radioactive and non-radioactive in situ hybridization and immunocytochemistry angiotensinogen mRNA, angiotensinogen, angiotensin II and, for the first time, N-terminal angiotensin fragment (1-7) immunoreactivities, respectively, were demonstrated in the rat cerebellum. Angiotensinogen mRNA and angiotensinogen immunoreactivity (IR) were both present in glial cell populations of all layers, especially in the Purkinje and granular cell layers and within the cerebellar nuclei. Angiotensin II IR was demonstrated in glial cell populations in all layers using a monoclonal angiotensin II antibody, while with a polyclonal angiotensin II antiserum (Denise) some Purkinje cell bodies were labelled. After lesioning the cerebellar cortex mechanically by an injection cannula a strong increase in angiotensinogen gene expression as well as in angiotensin II and angiotensin (1-7) immunoreactivities were observed in the glial cell populations. Furthermore, putative Bergmann glial processes, as indicated from the morphological appearance became strongly angiotensin II and angiotensinogen immunoreactive in the region close to the mechanically induced lesion. It could inter alia be demonstrated for the first time using confocal laser microscopy of ANG II IR and GFAP IR that ANG II in vivo in the intact cerebellar cortex is present in astroglial processes in the molecular layer and presumably secreted into the extracellular space in form of small spheric bodies and/or taken up by other cell types. In contrast, the N-terminal fragment angiotensin (1-7) IR was restricted to the glial cell populations and appeared only after the lesion event. Thus, it is suggested that the cerebellar RAS shows marked changes in response to mechanically induced lesions. The expression of angiotensinogen as well as the production of angiotensinogen IR and angiotensin II like IR is even after mechanical lesion restricted to astrocytes, i.e., cerebellar astrocytes and putative Bergmann glial cells, and in case of immunoreactivities it spreads to the radially oriented Bergmann glial processes in the molecular layer.

Angiotensin I↗
PubMed1994

Characterization of the macromolecular synthesis (MMS) operon from Listeria monocytogenes.

The macromolecular synthesis (MMS) operon consists of three genes: rpsU, which encodes the S21 ribosomal protein in Bacillus subtilis (Bs), rpsU is replaced by orfP23 which encodes a protein of unknown function), dnaG, encoding the DNA primase involved in the initiation of chromosome replication, and rpoD, which encodes the principal sigma subunit of RNA polymerase. The operon was cloned in three segments from Listeria monocytogenes (Lm), initially using a probe designed from a highly conserved region of RpoD. Analysis of the nucleotide sequence revealed three genes: orfP17 (whose product, P17, is homologous to Bs P23), dnaG and rpoD. The Lm DnaG resembles the primase from Escherichia coli through the first two-thirds of the sequence. C-terminal similarity was observed between DnaG from Lm and Bs. Lm RpoD is similar to Bs SigA, shares identical DNA-binding domains with SigA, and is a member of the sigma 43 subgroup of the sigma 70 family.

Amino Acid Sequence↗
PubMed1993

Regional expression of angiotensinogen mRNA in the brain of one-week-old, adult and old male rats.

The purpose of this study was to investigate possible regional differences in the distribution of angiotensinogen-mRNA in the postnatal versus the aging animal using in situ hybridization and computer-assisted microdensitometry. An essentially identical regional distribution pattern of angiotensinogen-mRNA in the brains of postnatal, adult and old rats was demonstrated. Substantial differences in angiotensinogen expression were observed in brain areas of postnatal versus adult and old animals. Also large differences were seen in the ratios of angiotensinogen-mRNA levels in different brain areas within one age. The medulla of young animals contained the largest amounts of angiotensinogen-mRNA compared to hypothalamus and midbrain. In contrast, adult and old animals showed approximately the same expression levels in midbrain and medulla, whereas the largest amounts of angiotensinogen-mRNA were expressed in the hypothalamus.

Aging↗
PubMed1993

Cellular localization of angiotensin type 1 receptor and angiotensinogen mRNAs in the subfornical organ of the rat brain.

The cellular localization of angiotensin type 1 receptor (AT 1) and angiotensinogen mRNA expression in the subfornical organ (SFO) of the rat brain has been studied by means of non-radioactive in situ hybridization combined with immunocytochemistry for glial fibrillary acidic protein (GFAP) and Neutral red staining. The AT 1 receptor mRNA expression is shown to be within putative nerve cells without any association with the glial fibrillary acidic protein (GFAP)-immunoreactive (IR) cells. In contrast the angiotensinogen cRNA expression is associated predominantly with GFAP-IR cells. The results demonstrate that a neuronal AT 1 receptor mediates the actions of circulating angiotensin II on the SFO and that the angiotensinogen mRNA is predominantly expressed in the SFO astroglial cells.

Angiotensin I↗
PubMed1993

A Monte Carlo model for retrospective analysis of shield design in a diagnostic x-ray room.

Recent recommendations by the NCRP and the ICRP have lowered the nonoccupational dose limit from 5 mSv y-1 to 1 mSv y-1 [corrected]. This change has also been incorporated in the recently revised Title 10 Code of Federal Regulations, Part 20. Shielding installed in most current diagnostic x-ray rooms was based on the 5-mSv limit when rooms or corridors adjacent to the x-ray room were unrestricted areas. A computer model for evaluating shielding in a diagnostic x-ray room has been developed using the following: the Monte Carlo Code MCNP, all materials that would normally attenuate the beam in an x-ray room, realistic assumptions for work load, and a spectrum of tube potentials based on actual usage. Results indicate that most radiographic x-ray rooms with shielding designed using the conservative assumptions in NCRP 49 will meet the new standards.

Evaluation Studies as Topic↗
PubMed1993

Leukaemic T cells from patients with chronic lymphocytic leukaemia of T-cell origin respond to Staphylococcus aureus enterotoxin superantigens.

We investigated the in vitro responsiveness of peripheral blood lymphocytes from two patients with T-cell chronic lymphocytic leukaemia (T-CLL) to Staphylococcus aureus enterotoxin (SE) superantigens. T-cell receptor (TcR) alpha beta (V beta 7.1)-expressing CD4+ leukaemic T cells from patient HE (white blood cell count 480,000/microliters) proliferated in response to SEA and, only at 1000-fold higher concentrations, to SEB, SED, and SEE. CD4+CD8+ TcR alpha beta (V beta 12.1)-expressing leukaemic T cells from patient KO (white blood cell count 120,000/microliters) were activated by SEB but not by the other tested SEs. In both instances, the activation of leukaemic T cells by SE was dependent on the presence of HLA-DR+ cells. Southern blot analysis of TcR beta gene rearrangement confirmed that the proliferating cells were derived from the leukaemic T-cell clone and not from contaminating normal T cells. These data indicate that leukaemic T cells from patients with T-CLL exert a clonally variable responsiveness to SE superantigens. We conclude that recognition of specific antigen and subsequent signal transduction can be initiated via the TcR of leukaemic T-CLL cells.

Antigens, Bacterial↗
PubMed1993

Ontogenetic regulation of mouse Ren-2d renin gene in transgenic hypertensive rats, TGR(mREN2)27.

TGR(mREN2)27 is a new monogenetic rat model with fulminant hypertension, low kidney renin, and high extrarenal renin gene expression. This study characterizes and compares expression of the Ren-2 gene in TGR(mREN2)27 with that in DBA/2 mice and with renin gene expression in rats. Except in the submandibular gland, the tissue-specific expression of Ren-2 is similar in TGR(mREN2)27 and DBA/2. This demonstrates maintenance of tissue specificity. Organs that are involved in cardiovascular regulation, such as the adrenal gland, kidney, and brain, express the Ren-2 gene before hypertension has developed, consistent with the possibility of a causal relationship between transgene expression in these tissues and hypertension. Because these tissues express the renin gene in nontransgenic rats as well, we suggest that this model can be used to study the regulation of renin gene expression and its role in hypertension at these sites. In addition, as an indication that interactions may exist between blood pressure and renin gene expression, we describe reciprocal changes in blood pressure and Ren-2 mRNA levels in the kidney and brain.

Adrenal Glands↗
PubMed1993

Glucocorticoid regulation of angiotensinogen gene expression in discrete areas of the male rat brain. An in situ hybridization study.

The regulation of angiotensinogen gene expression by glucocorticoids has been described in several studies. Kalinyak and Perlman reported on a 60% increase of angiotensinogen expression in the rat brain after dexamethasone treatment with a single, high-dose injection. The purpose of the present study was to investigate whether a general upregulation of angiotensinogen expression or a region-specific upregulation underlies these findings. By using in situ hybridization and computer-assisted microdensitometry we evaluated the regional changes in angiotensinogen expression following dexamethasone treatment. Angiotensinogen expression was strongly stimulated in several areas (medial septum and locus ceruleus), while only moderately in others (hypothalamus, medulla). An interesting finding is the difference in glucocorticoid receptor regulation among the circumventricular organs. The subfornical organ displayed no changes in angiotensinogen-mRNA, whereas the area postrema showed an increase. Furthermore, the angiotensinogen expression in the median eminence decreased substantially. The nature of these effects will form the subject of further investigations. In conclusion we demonstrated an overall increase but certain heterogeneities in angiotensinogen expression after dexamethasone treatment, a pattern which suggests different degrees of glucocorticoid receptor regulation of the angiotensinogen gene in certain areas of the brain, probably mainly dependent on the degree of glial glucocorticoid receptor presence.

Angiotensinogen↗
PubMed1992

The distribution of angiotensin II AT1 receptor subtype mRNA in the rat brain.

The present study demonstrates the existence and regional distribution of angiotensin II AT1 receptor subtype mRNA expression in the rat brain by the use of in situ hybridization and RNase protection assay. Substantial expression levels in the brain have only been detected in certain distinct areas, such as the subfornical organ, the parvocellular part of the paraventricular hypothalamic nucleus, and the median preoptic nucleus. The results give further evidence for the involvement of the angiotensin II AT1 receptor subtype in the classical functions of central angiotensin II, like blood pressure control, body fluid homeostasis and in corticotropin-releasing factor (CRF) secretion.

Angiotensin II↗
PubMed1992

Gene and pseudogene of the mouse cation-dependent mannose 6-phosphate receptor. Genomic organization, expression, and chromosomal localization.

The cation-dependent mannose 6-phosphate receptor (CD-MPR) is one of the two transmembrane proteins involved in transport of lysosomal enzymes. We have cloned the mouse CD-MPR gene and also a very unusual processed-type CD-MPR pseudogene. They are both present at one copy per haploid genome and map to chromosomes 6 and 3, respectively. Comparison of the complete 10-kilobase (kb) sequence of the functional gene with the cDNA indicates that it contains seven exons. Exon 1 encodes the 5'-untranslated region of the mRNA, the others (exons 2-7) encode the luminal, transmembrane, and cytoplasmic domains of the CD-MPR. Exon 7 also contains a 1.2-kb-long 3'-untranslated region of the mRNA. A unique transcription-initiation site was determined by primer extension of mouse liver mRNA. The promoter elements in the 5' upstream region of this site resemble those contained in genes constitutively transcribed. However, Northern blot analysis demonstrates that the CD-MPR is variably expressed in adult mouse tissues and during mouse development. The pseudogene, which is flanked by direct repeats, is almost colinear with the cDNA indicating that it presumably arose by reverse transcription of an mRNA. However, the pseudogene differs from the cDNA. It contains at its 5' end, an additional 340-nucleotide (nt) sequence homologous to the promoter region of the functional gene. This sequence exhibits some promoter activity in vitro. Furthermore, a 24-nt insertion interrupts the region homologous to the 5'-noncoding region of the cDNA. In the functional gene, this 24-nt sequence occurs between exon 1 and 2, where it is flanked by typical consensus sequences of exon/intron boundaries. Therefore, it may represent an additional exon of the functional gene. These two features of the pseudogene suggest that expression of the CD-MPR gene may be regulated by use of different promoters and/or alternative splicing.

Amino Acid Sequence↗