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J Peters

Publications and source records attributed to J Peters.

At least 109 records · Page 6Linked to original sources
PubMed2001

Effects of all-trans retinoic acid on renin-angiotensin system in rats with experimental nephritis.

We previously demonstrated that all-trans retinoic acid (RA) preserves glomerular structure and function in anti-Thy1.1 nephritis (Wagner J, Dechow C, Morath C, Lehrke I, Amann K, Floege J, and Ritz E. J Am Soc Nephrol 11: 1479-1489, 2000). Because the renin-angiotensin system (RAS) contributes to renal damage, we 1) studied retinoid-specific effects on its components and 2) compared the effects of all-trans-RA with those of the AT(1)-receptor blocker candesartan. Rats were pretreated for 3 days before injection of the OX-7 antibody and continued with treatment with either vehicle or daily injections of 10 mg/kg all-trans-RA only (study 1) or 10 mg/kg body wt all-trans-RA, 1 mg/kg candesartan, or both (study 2) for an additional 7 days. The blood pressure increase observed in anti-Thy1.1 nephritic rats was equally normalized by all-trans-RA and candesartan (P < 0.05). In nephritic rats, mRNAs of angiotensinogen and angiotensin-converting enzyme (ACE) in the kidney were unchanged, but renin mRNA was lower (P < 0.01). Renal and glomerular AT(1)-receptor gene and protein expression levels were higher in anti-Thy1.1 nephritic rats (P < 0.05). In the renal cortex of nephritic rats, pretreatment with all-trans-RA significantly reduced mRNAs of all the examined RAS components, but in the glomeruli it increased ACE gene and protein expression (P < 0.01). In nephritic rats, candesartan reduced the number of glomerular cells and mitoses (P < 0.05) less efficiently than all-trans-RA (P < 0.01). Both substances reduced cellular proliferation (proliferating cell nuclear antigen) significantly (P < 0.05). No additive effects were noted when both compounds were combined. In conclusion, all-trans-RA influences the renal RAS in anti-Thy1.1 nephritis by decreasing ANG II synthesis and receptor expression. The beneficial effect of retinoids may be explained, at least in part, by reduction of RAS activity.

Angiotensin II↗
PubMed2001

Baroreceptor modulation of active cutaneous vasodilation during dynamic exercise in humans.

The hypothesis that baroreceptor unloading during dynamic limits cutaneous vasodilation by withdrawal of active vasodilator activity was tested in seven human subjects. Increases in forearm skin blood flow (laser-Doppler velocimetry) at skin sites with (control) and without alpha-adrenergic vasoconstrictor activity (vasodilator only) and in arterial blood pressure (noninvasive) were measured and used to calculate cutaneous vascular conductance (CVC). Subjects performed two similar dynamic exercise (119 +/- 8 W) protocols with and without baroreceptor unloading induced by application of -40 mmHg lower body negative pressure (LBNP). The LBNP condition was reversed (i.e., either removed or applied) after 15 min while exercise continued for an additional 15 min. During exercise without LBNP, the increase in body core temperature (esophageal temperature) required to elicit active cutaneous vasodilation averaged 0.25 +/- 0.08 and 0.31 +/- 0.10 degrees C (SE) at control and vasodilator-only skin sites, respectively, and increased to 0.44 +/- 0.10 and 0.50 +/- 0.10 degrees C (P < 0.05 compared with without LBNP) during exercise with LBNP. During exercise baroreceptor unloading delayed the onset of cutaneous vasodilation and limited peak CVC at vasodilator-only skin sites. These data support the hypothesis that during exercise baroreceptor unloading modulates active cutaneous vasodilation.

Adrenergic alpha-Antagonists↗
PubMed2001

Changes of AT(2) receptor levels in the rat adrenal cortex and medulla induced by bilateral nephrectomy and its modulation by circulating ANG II.

We studied regulation of the AT(2) receptor by investigating the effect of bilateral nephrectomy (bNX) in Sprague-Dawley rats. The expression of aldosterone synthase (CYP11B2) and AT(2) receptor mRNA was detected by nonradioactive in situ hybridization. AT(2) receptor mRNA was detected in cells of the first two or three subcapsular cell layers of the zona glomerulosa (ZG) and in the medulla of sham-operated animals. After bNX, the number and area of distribution of AT(2) receptor-positive cells increased in the ZG. This was associated with an enlargement of the steroidogenic active ZG and with reduced proliferation rate (sham 5.9 +/- 0.9%; bNX 2.4 +/- 0.2%; p<0.02). Infusion of angiotensin II (ANG II; 200 ng/kg/min SC for 56 hr) to bNX rats did not reverse the effect of nephrectomy on the distribution of AT(2) receptor expression, although mRNA levels per cell were reduced compared to NX alone. ANG II infusion decreased proliferation rate further (0.4 +/- 0.07%; p<0.001). In the adrenal medulla after bNX, decreased expression of the AT(2) receptor was associated with increased proliferation (2.6 +/- 0.2% vs 6.6 +/- 0.5%). These results demonstrate differential regulation of the AT(2) receptor in the adrenal gland and suggest that expression of the AT(2) receptor is involved in regulating proliferation and differentiation in the ZG and medulla. (J Histochem Cytochem 49:649-656, 2001)

Adrenal Cortex↗
PubMed2001

Caring for dry and damaged skin in the community.

Community nurses are ideally place to fully utilize nurse prescribing to improve the accessibility to emollient therapy for any patient with dry skin, regardless of cause. Skin diseases affect 23% of the general population and patients accessing care in the primary setting contribute to 15-20% of general practice appointments.

Community Health Nursing↗
PubMed2001

Resistance of cattle to scrapie by the oral route.

Early epidemiological information indicated that bovine spongiform encephalopathy (BSE) originated from scrapie in sheep. The question arose if scrapie in North America would induce a BSE-like disease in cattle. Six years ago, we reported that brain tissue from sheep with scrapie caused a neurologic disease when injected directly into the brains of cattle, but the disease induced was different from BSE as it occurs in the United Kingdom and Europe. Here, we report that cattle fed raw brain or meat and bone meal and tallow prepared from sheep with scrapie remained normal for 8 years after exposure. This work indicates that cattle are highly resistant to North American scrapie by the oral route.

Animals↗
PubMed2001

["Phtisis atra"--a now seldom disease picture as a special disease course of silicosis].

Progressive massive fibrosis (PMF) of the lung is caused by coalescence of fibrotic nodules. The center of the PMF often displays necrotic areas. If the necrosis gets in contact to the bronchial system cavitation may occur. We report on a 68 year old patient suffering from severe silicosis of the lung and metastatic spread of a histologically proven lung cancer into the brain. The patient who was administered to the hospital under the intention of cerebral radiotherapy showed a colliquative PMF in the right upper lobe with cavitation and expectoration of large amounts of black-stained sputum (melanoptysis).

Adenocarcinoma↗
PubMed2001

Good Medical Practice: comparing the views of doctors and the general population.

OBJECTIVES: To assess the views of the general public and general practitioners (GPs) on the General Medical Council's Good Medical Practice. METHODS: A large national consumer survey organization (MORI) was commissioned to conduct a survey of a representative sample of the general public using quota sampling methods with randomly selected sampling points across Great Britain. A similar survey was carried out of GPs across Great Britain. Questions were asked of the general public about their perceptions on medical practitioners keeping their knowledge sufficiently up to date to do their job, on complaints being properly investigated, and about doctors being removed from the General Medical Council register if they failed to perform a specifically defined duty. The GPs were asked the same questions about duties. The general public was also asked whether they worked in the National Health Service (NHS), about any recent experiences as a patient in the NHS and whether they had ever complained about a doctor. RESULTS: A total of 1949 people were interviewed in their homes along with 199 GPs. Over one-third either worked in the NHS or had friends or relatives who worked in the NHS. Eleven per cent felt they had reason to complain about a doctor although only 6% had made a formal or informal written or verbal complaint. The general public and GPs held similar views on reasons for doctors being removed from the register, although the public's threshold was somewhat lower than the doctors. CONCLUSIONS: GPs and the general public have similar views on good medical practice, although the degree of concern shown by the public is greater than that registered by doctors. Both groups show similar patterns of variation in their perception of the importance of some duties compared with others.

Adolescent↗
PubMed2000

Improving the refolding yield of interleukin-4 through the optimization of local interactions.

Interleukin-4 (IL-4) is a multifunctional cytokine that plays an important role in the regulation of various immune responses. However, the development of IL-4 or IL-4 variants into potential therapeutic drugs is hindered by the low efficiency of the in vitro refolding process of this protein. In this work, we have investigated the improvement of the refolding yield of IL-4 using two different rational design approaches. The first one is based on the so-called inverse hydrophobic effect and involved the replacement of a solvent exposed, non-conserved, hydrophobic residue (W91) by serine. This led to an increase in stability of 1.4 kcal mol(-1) and shifted the midpoint transition temperature (Tm) from 62 to 70 degrees C. The second approach is based on the stabilization of alpha-helices through the introduction of favorable local interactions. This strategy resulted in the following helix sequence for helix C of IL-4, 68ASAAEANRHKQLIRFLKRLDRNLWGLAG95. The mutant protein was stabilized by 0.5 kcal mol(-1), the Tm shifted to 68 degrees C, and a two-fold increase in the refolding yield was consistently observed. Our results make the large-scale production of IL-4 derivatives economically more viable, suggest that a similar approach can be applied to other related proteins, and may represent a general strategy to improve in vitro refolding yields through the selective optimization of the stability of alpha-helices.

Amino Acid Sequence↗
PubMed2000

Two imprinted gene mutations: three phenotypes.

Genetic modifications of imprinted genes have been generated in the mouse to investigate the regulation of their expression. They show classical imprinted gene inheritances. Here we describe two imprinted gene mutations deriving from mutagenesis experiments. One is expressed only when transmitted through males. It causes a prenatal growth retardation which resembles that of the Igf2 knockout and maps close to the locus on chromosome 7. Differences from the knockout, which include an abnormal head phenotype, homozygous lethality, and an inability to rescue a TME: (Igf2r-deficient) lethality, suggest that Igf2 itself may not be directly affected. The second mutation maps close to the GNAS: cluster of imprinted genes on distal chromosome 2. It gives two distinct phenotypes according to parental origin, a gross neonatal oedema with microcardia and a postnatal growth retardation. The oedema phenotype is effectively lethal and resembles that of mice with paternal partial disomy for distal chromosome 2, as well as that of mice having a maternally derived GNAS: exon 2 knockout. However, the second growth retardation phenotype differs from that of the maternal partial disomy and the paternal knockout. A hypothesis to explain the phenotypes associated with the three genotypes based on the NESP:/NESPAS: sense/antisense and GNASXL: transcripts in the GNAS: cluster is offered.

Aneuploidy↗
PubMed2000

Identification of two new Pmp22 mouse mutants using large-scale mutagenesis and a novel rapid mapping strategy.

Mouse mutants have a key role in discerning mammalian gene function and modelling human disease; however, at present mutants exist for only 1-2% of all mouse genes. In order to address this phenotype gap, we have embarked on a genome-wide, phenotype-driven, large-scale N-ethyl-N--nitrosourea (ENU) mutagenesis screen for dominant mutations of clinical and pharmacological interest in the mouse. Here we describe the identification of two similar neurological phenotypes and determination of the underlying mutations using a novel rapid mapping strategy incorporating speed back-crosses and high throughput genotyping. Two mutant mice were identified with marked resting tremor and further characterized using the SHIRPA behavioural and functional assessment protocol. Back-cross animals were generated using in vitro fertilization and genome scans performed utilizing DNA pools derived from multiple mutant mice. Both mutants were mapped to a region on chromosome 11 containing the peripheral myelin protein 22 gene (Pmp22). Sequence analysis revealed novel point mutations in Pmp22 in both lines. The first mutation, H12R, alters the same amino acid as in the severe human peripheral neuropathy Dejerine Sottas syndrome and Y153TER in the other mutant truncates the Pmp22 protein by seven amino acids. Histological analysis of both lines revealed hypo-myelination of peripheral nerves. This is the first report of the generation of a clinically relevant neurological mutant and its rapid genetic characterization from a large-scale mutagenesis screen for dominant phenotypes in the mouse, and validates the use of large-scale screens to generate desired clinical phenotypes in mice.

Animals↗
PubMed2000

Mechanisms of arachidonic acid induced glial swelling.

Accumulation of arachidonic acid (AA) in the brain during ischaemia may contribute to development of brain oedema. In this study we investigated the effect of selected drugs on AA-induced cytotoxic brain oedema in C6 glioma cells. Suspended C6 glioma cells were preincubated with drugs and AA (0.1 mM) was added. When no drug was administered cell volume increased immediately after the addition of AA with a maximum cell swelling of 13.1+/-1.9% at 15 min (mean +/- S.E. M.). Preincubation of cells with BW 755C, a dual inhibitor of cyclo- and lipoxygenases, showed no reduction in cell swelling from AA, whereas superoxide dismutase, amiloride and the protein kinase inhibitor H-9370 led to a significant attenuation of volume increase (p<0.05). The role of Na(+) ions during cell swelling from AA was evaluated after pretreatment of C6 glioma cells with ouabain. This resulted in a reversal of cell swelling (p<0.01). We conclude that there is potential involvement of free radicals, signal transduction systems and intracellular accumulation of Na(+) ions in glial cell swelling from AA.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed2000

An imprinted transcript, antisense to Nesp, adds complexity to the cluster of imprinted genes at the mouse Gnas locus.

The Gnas locus in distal mouse chromosome (Chr) 2 is emerging as a complex genomic region. It contains three imprinted genes in the order Nesp-Gnasxl-Gnas. Gnas encodes a G protein alpha-subunit, and Nesp and Gnasxl encode proteins of unknown function expressed in neuroendocrine tissue. Together, these genes form a single transcription unit because transcripts of Nesp and Gnasxl are alternatively spliced onto exon 2 of Gnas. Nesp and Gnasxl are expressed from opposite parental alleles, with Nesp encoding a maternal-specific transcript and Gnasxl encoding a paternal-specific transcript. We now identify a further imprinted transcript in this cluster. Reverse transcription-PCR analysis of Nesp expression in 15. 5-days-postcoitum embryos carrying only maternal or paternal copies of distal Chr 2 revealed an isoform that is exclusively paternally, rather than maternally, expressed. Strand-specific reverse transcription-PCR showed that this form is an antisense transcript. The existence of a paternally expressed antisense transcript was confirmed by Northern blot analysis. The sequence is contiguous with genomic sequence downstream of Nesp and encompasses Nesp exons 1 and 2 and an intervening intron. We propose that Nespas is an additional control element in the imprinting region of mouse distal Chr 2; it adds further complexity to the Gnas-imprinted gene cluster.

Animals↗
PubMed2000

Inhaled beta-agonists for asthma in mechanically ventilated patients.

BACKGROUND: A small number of patients with acute severe asthma require intubation and positive pressure ventilation. The beneficial effects of inhaled bronchodilators on acute asthma in spontaneously breathing subjects are well established, but there remain important questions regarding inhaled beta2-agonists, for patients who are intubated and receiving ventilation. OBJECTIVES: To determine the effects of inhaled beta-agonists on asthmatic patients who require intubation and mechanical ventilation. SEARCH STRATEGY: Randomised controlled trials were sought from the Cochrane Airways Group Asthma Register. Primary authors and content experts were contacted to identify eligible studies and bibliographies from known reviews and texts were searched. SELECTION CRITERIA: Randomised, controlled clinical trials involving adult patients with acute asthma, who were intubated and supported with positive pressure ventilation. Studies were to be included if patients were treated with beta2-adrenergic agonist agents and there was a comparator group treated with either placebo, no medication, or 'standard' treatment. DATA COLLECTION AND ANALYSIS: Two reviewers independently examined all identified articles. The full text of any potentially relevant article was reviewed independently by two reviewers. MAIN RESULTS: The search yielded 152 abstracts. Of these, four articles were identified as potential trials. None of the four trials met the inclusion criteria for the review. REVIEWER'S CONCLUSIONS: There are no data from randomised controlled trials to provide evidence for or against current practices regarding the use of inhaled beta2-agonists in asthmatic subjects who are intubated and ventilated.

Acute Disease↗
PubMed2000

Effects of haemoconcentration and haemodilution on acute hypoxia-induced pulmonary hypertension and changes in vascular compliance of isolated rabbit lungs.

OBJECTIVE: Erythrocytes influence the magnitude of hypoxia-induced pulmonary artery pressure increase. It is, however, unknown to what extent haemoconcentration and haemodilution affect this response and whether intrapulmonary blood volume (and thus vessel dimensions) alters the magnitude of pressure increase. Furthermore, it is unclear whether the haemodilution/ haemoconcentration-dependent pressure increase is flow-related, via flow-dependent changes in vasomotor tone or rheologic effects, or can also be observed under no-flow conditions. DESIGN: Experimental study in isolated rabbit lungs (n = 12) perfused with autologous blood at constant flow (100 ml/min) and ventilated with 5% carbon dioxide in air. SETTING: Laboratory for experimental studies. INTERVENTIONS: Haemoconcentration (centrifugation) and haemodilution (Krebs-Henseleit/albumin) were carried out, resulting in haematocrits between 50% and 0%. During hypoxic ventilation, inspiratory oxygen fraction was reduced from 0.20 to 0.03. MEASUREMENTS AND RESULTS: Under constant flow conditions, haemodilution (from a Hct of 34-36% to 0-1%) decreased hypoxic pulmonary artery pressure response to one-third (from 10.8 +/- 2.3 cmH2O to 3.1 +/- 1.0 cmH2O, P < 0.05), while haemoconcentration did not affect the magnitude of hypoxic response (10.5 +/- 2.0 cmH2O). For all haematocrit values an increase in pulmonary blood volume (by 5 ml) decreased the magnitude of pressure response. Hypoxia-induced changes in static vascular filling pressure (double occlusion pressure) and vascular compliance were used to assess the strength of hypoxic vasoconstriction under static conditions. Neither haemoconcentration nor haemodilution altered hypoxia-induced changes in either variable. CONCLUSIONS: The magnitude of the acute hypoxic pressure response is not altered by haemoconcentration, but significantly reduced by haemodilution. In contrast, neither haemoconcentration nor haemodilution influenced hypoxia-induced changes in static vascular filling pressure and compliance. This suggests that the degree of hypoxic pulmonary vasoconstriction is not affected under static conditions and that the red blood cell-dependence of the magnitude of hypoxic pressure response is based on flow-related mechanisms.

Analysis of Variance↗
PubMed2000

Implementation of a large-scale ENU mutagenesis program: towards increasing the mouse mutant resource.

Systematic approaches to mouse mutagenesis will be vital for future studies of gene function. We have begun a major ENU mutagenesis program incorporating a large genome-wide screen for dominant mutations. Progeny of ENU-mutagenized mice are screened for visible defects at birth and weaning, and at 5 weeks of age by using a systematic and semi-quantitative screening protocol-SHIRPA. Following this, mice are screened for abnormal locomotor activity and for deficits in prepulse inhibition of the acoustic startle response. Moreover, in the primary screen, blood is collected from mice and subjected to a comprehensive clinical biochemical analysis. Subsequently, secondary and tertiary screens of increasing complexity can be used on animals demonstrating deficits in the primary screen. Frozen sperm is archived from all the male mice passing through the screen. In addition, tail tips are stored for DNA. Overall, the program will provide an extensive new resource of mutant and phenotype data to the mouse and human genetics communities at large. The challenge now is to employ the expanding mouse mutant resource to improve the mutant map of the mouse. An improved mutant map of the mouse will be an important asset in exploiting the growing gene map of the mouse and assisting with the identification of genes underlying novel mutations-with consequent benefits for the analysis of gene function and the identification of novel pathways.

Animals↗