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Biomedical subjects

M Peters

Publications and source records attributed to M Peters.

At least 217 records · Page 12Linked to original sources
PubMed1997

Silica-induced apoptosis in alveolar and granulomatous cells in vivo.

Silica is a toxicant that can stimulate cells to produce various cellular products such as free radicals, cytokines, and growth factors. Silica and its induced substances may induce apoptosis to regulate the evolution of silica-induced inflammation and fibrosis. To examine this hypothesis, groups of Wistar male rats were intratracheally instilled with different doses of Min-U-Sil 5 silica (Silica, Berkeley Springs, WV). Ten days after the instillation, we obtained cells by bronchoalveolar lavage and placed them on slides by cytospin preparation. The slides were stained with Diff-Quik (Lab Aids, Sydney, NSW, Australia) and examined under oil immersion. A substantial number of cells with apoptotic features were identified in all silica-instilled rats and the apoptosis was confirmed by agarose gel electrophoresis. The number of apoptotic cells was clearly related to silica dosage. Engulfment of apoptotic cells by macrophages was also noted. Neutrophil influx in silica-instilled rats could be saturated with the increase of silica dosage and the number of macrophages in different dose groups changed in parallel with the proportion of apoptotic cells. Fifty-six days after instillation, morphologically apoptotic cells could be identified in granulomatous cells of lung tissue from silica-instilled rats. We conclude that intratracheal instillation of silica could induce apoptosis in both alveolar and granulomatous cells, and the apoptotic change and subsequent engulfment by macrophages might play a role in the evolution of silica-induced effects.

Administration, Inhalation↗
PubMed1997

Anxiety coping style and daily blood pressure variation of female nurses.

OBJECTIVE: To examine how the style of coping with anxiety influences ambulatory blood pressures measured in work and home environments for 63 women aged 34 +/- 8 years employed as nurses. METHODS: Awake ambulatory blood pressures measured at work (n = 38 readings) and at home (n =7 readings) were compared among nurses who had been classified as belonging to four anxiety-coping-style groups: low anxious repressive (n = 18 work, n = 16 home), high anxious defensive (n = 4 work, n = 4 home) true low anxious (n = 21 work, n = 20 home) and true high anxious (n = 19 work, n = 18 home). The four anxiety-coping-style groups were determined by cross-classifying the women upon the basis of their scores on the Marlowe-Crowne Social Desirability Scale (cutoff at 18) and the Taylor Manifest Anxiety Scale (cutoff at 14). RESULTS: Average systolic blood pressures at work and at home among nurses with a low anxious repressive coping style were significantly lower than were those of nurses with a high anxious defensive coping style (P < 0.05) and a true low anxious coping style ( P < 0.025). Nurses with a low anxious repressive coping style also had lower diastolic blood pressures at work than did those with a high anxious defensive coping style ( P < 0.05) and lower diastolic blood pressures at home than did those with a true anxious coping style ( P < 0.01). Finally, subjects with a high anxious defensive coping style had significantly higher systolic blood pressures at work and at home (P < 0.05) and higher diastolic blood pressures at work than did nurses with a true high anxious coping style. The effects of the style of coping on the variation of work and home blood pressures were independent of several covariates including weight, perceived stress, smoking, alcohol, postural variation, and number of children. The univariate scales of Social Desirability and Anxiety also had no effect on the variability of the blood pressure. CONCLUSION: Among employed women, the extent of the reponse of the blood pressure to stresses in the work and home environments could be infoluenced by the style of coping with anxiety. Furthermore, the effects of personality constructs such as the style of coping, which are defined by the interaction of psychologic dimensions, may reflect better the complexity of behavioral influences on the blood pressure than do the univariate psychometric measures of which they are composed.

Journal Article↗
PubMed1997

Recombinant, B-domain deleted factor VIII (r-VIII SQ): pharmacokinetics and initial safety aspects in hemophilia A patients.

The pharmacokinetics of a second-generation recombinant B-domain deleted factor VIII (FVIII) preparation (r-VIII SQ) were studied in 36 patients with severe hemophilia A. In contrast to full-length recombinant FVIII, no albumin needs to be added to stabilize the final formulation of this B-domain deleted FVIII preparation. The in vivo recovery and half-life of r-VIII SQ were similar to those of plasma-derived (pd) FVIII (mean half-life of r-VIII SQ, 11.7 h). The volume of distribution and clearance were slightly, but significantly, higher for r-VIII SQ than for pdFVIII (p < 0.05). Peak plasma levels of FVIII were consistently related to the administered dose of r-VIII SQ (r = 0.94, p < 0.0001). The pharmacokinetic profile of r-VIII SQ remained essentially unchanged in a dose range of 25-100 IU/kg body weight and could be reproduced after repeated doses. r-VIII SQ was well tolerated. In conclusion, deletion of the B-domain of FVIII does not influence its in vivo pharmacokinetics.

Adolescent↗
PubMed1997

[Neospora caninum causes abortions in a cattle herd in North Rhine Westphalia].

In a cattle herd in North Rhine-Westphalia a series of eight abortions occurred between 15th August and 14th October, 1996. Four of the aborted fetuses were histopathologically, virologically, bacteriologically and parasitologically examined. A multifocal necrotising encephalitis was observed in two fetuses. In addition, the liver of two fetuses and the placenta of one fetus contained infected foci. In three fetuses protozoan stages were detected which were identified as N. caninum by immunohistochemistry. A polymerase chain reaction conducted with histological material revealed N. caninum-DNA in the placenta of an aborted fetus. When seven cows that had aborted were tested for antibodies directed against N. caninum, six animals were positive by immunofluorescence and all seven by immunoblotting. The serological examination of the entire herd revealed a high herd seroprevalence of antibodies directed against N. caninum. Potential modes of infection with N. caninum in the herd are discussed, in particular the possibility of exposure to a point source (definitive host).

Abortion, Veterinary↗
PubMed1997

Antithrombin acts as a negative acute phase protein as established with studies on HepG2 cells and in baboons.

Patients with sepsis or after major surgery have decreased plasma levels of the anticoagulant protein antithrombin. In such patients elevated levels of interleukin-6 (IL-6) are present and this interleukin is known to induce positive and negative acute phase responses. To investigate the possibility that antithrombin acts as a negative acute phase response-protein we performed studies on the human hepatoma cell line HepG2 in vitro and baboons in vivo. HepG2 cells were treated with recombinant human IL-6, IL-1beta, or combinations of the latter two, and tested for production of antithrombin, fibrinogen and prealbumin (transthyretin). This treatment resulted in a dose dependent increase in fibrinogen concentration (with a maximum effect of 2.8-2.9-fold) and a dose dependent decrease in prealbumin (with a maximum effect of 0.6-0.7-fold) and antithrombin concentrations (with a maximum effect of 0.6-0.8-fold). Simultaneous treatment of the HepG2 cells with IL-6 (1,000 pg/ml or 2,500 pg/ml) and IL-1beta (25 pg/ml), provided more extensively decreased prealbumin (0.8 and 0.6-fold, respectively) and antithrombin concentration (0.7 and 0.6-fold, respectively) compared to the single interleukin treatment at these concentrations. Baboons treated with 2 microg IL-6 x kg body-weight(-1) x day(-1) showed increased plasma CRP levels (59-fold, p <0.05) and decreased prealbumin (0.9-fold, p <0.05) and antithrombin (0.8-fold, p <0.05) plasma levels, without evidence for coagulation activation. Our results indicate that antithrombin acts as a negative acute phase protein, which may contribute to the decreased antithrombin plasma levels observed after major surgery or in sepsis.

Acute-Phase Reaction↗
PubMed1997

[Chemical accident with isoproturone in an industrial plant in Frankfurt am Main 27 January 1996].

On 27 January 1996, about 1 ton of Isoproturone was released into the atmosphere due to an accident in a chemical plant located at Frankfurt-Griesheim, Germany. A nearby residential area was contaminated by up to 500 mg Isoproturon/m2. According to the published toxicological data and the contamination data, model calculations were performed demonstrating that the individual exposure remained below the LOEL. For better exposure and risk assessment urine biomonitoring was offered to the residents. HMEPMH, the main metabolite of Isoproturon was detected in 12% (19/154) of the participants in the test, with a maximum value of 14.2 micrograms/l, i.e. the internal exposure remained even below ADI. Control tests demonstrated the decrease of the soil contamination after some weeks, and by June 1996 Isoproturone was no longer detectable, neither in soil nor in vegetables.

Accidents, Occupational↗
PubMed1996

Yeast expression of the cytokine receptor domain of the soluble interleukin-6 receptor.

The complex of the soluble interleukin-6 receptor (sIL-6R) and IL-6 (IL-6) is a potent agonist on cells expressing the signal transducing protein gp 130. In contrast, IL-6 alone only stimulates cells which express a membrane bound form of the IL-6R and gp 130. The natural occurring sIL-6R is generated by shedding of the membrane receptor and to a lesser extend by alternative splicing. We have inserted the coding sequence of the 323 amino acid residues of the human sIL-6R into an expression/secretion vector suitable for the methylotrophic yeast Pichia pastoris. We obtained, however, no detectable expression and secretion of the recombinant protein. When we used only the coding sequence of the cytokine receptor domain of the sIL-6R for the construction of an expression plasmid, this truncated version of the sIL-6R accumulated in the supernatant to 1-5 mg/l. The protein was purified by a single affinity chromatography step using a monoclonal antibody directed against the human IL-6R. Following the same approach, we expressed a truncated splice variant of the sIL-6R. Both, the secreted truncated sIL-6R and the splice variant showed full agonistic biological activity on human hepatoma cells. The described expression strategy will be useful for large scale production of biologically active sIL-6R and might be adapted for the expression of other members of the hematopoietic cytokine receptor family.

Antigens, CD↗
PubMed1996

Ligand-dependent enhancement of human antithrombin gene expression by retinoid X receptor alpha and thyroid hormone receptor beta.

We studied potential modulators of antithrombin gene expression. A putative hormone response element (HRE) was identified by sequence similarity analysis of the antithrombin promoter, situated between nucleotides -92 and -54 relative to the transcription start site. This HRE contains three hexa-nucleotide motifs with an AGGTCA consensus, which are potential targets of members of the steroid/thyroid superfamily of nuclear receptors. Stimulation of the hepatoma cell line HepG2 with the receptor ligands L-3,5,3'-tri-iodothyronine, all-trans retinoic acid, or their combination, increased production of antithrombin into the culture medium by 1.3-, 1.6-, and 2.0-fold, respectively. In contrast, the receptor ligand 1,25-dihydroxy-cholecalciferol[1,25-(OH)2VitD3] did not influence antithrombin production. Analysis of promoter chloramphenicol acetyl-transferase (CAT) constructs, showed that the first 86 bp of the antithrombin promoter region are sufficient for basal transcription. The DNA length polymorphism of 32 bp or 108 bp, located upstream of position -276, did not influence anti-thrombin promoter activity. The antithrombin promoter activity dropped to background values when deleting the region -97/-49 of promoter fragment -453/+57. Transactivation of the antithrombin promoter by retinoid X receptor alpha (RXR alpha) (5-7-fold) or thyroid hormone receptor beta (TR beta) (4-5-fold) was only observed when at least -167/+57 bp of the promoter region is present in CAT constructs, and when the appropriate ligand of the nuclear receptor was added. This transactivation was not observed upon deletion of the antithrombin promoter region -97/-49. With three copies of the antithrombin promoter fragment -109/-42 in front of the thymidine kinase minimal promoter, transactivation was only obtained with RXR alpha, and not with TR beta. In conclusion, these results indicate that the ligand-dependent enhancement of antithrombin gene expression is regulated by RXR alpha as well as by TR beta. Transactivation of antithrombin gene expression by RXR alpha and TR beta appears to be dependent upon the presence of promoter region up to nucleotide -167. The HRE segment (-109/-42) only confers RXR alpha responsiveness to a heterologous promoter. Further study is needed to unravel the exact nature of this HRE and its 5'-flanking sequences.

Antithrombin III↗
PubMed1996

[An infant with a fatal cerebral hemorrhage due to vitamin K deficiency].

A 7-week old, male infant died from an intracerebral haemorrhage due to vitamin K deficiency. He had been exclusively breast-fed. Directly after birth no vitamin K was administered. From day 10 a daily dose of 25 microgram vitamin K was given orally. At post mortem a mild cholestasis was found which may have been an additional factor contributing to late vitamin K deficiency.

Breast Feeding↗
PubMed1996

The clinical interface--a British physician's view.

There appears to be a growing divergence, in the UK, between the hospital clinician and laboratory specialist as to their respective roles in the investigation of patients. The clinician requires a prompt service based on effective communication systems and rapid turnaround of test results. Laboratory specialists generally perceive both their role and that of the laboratory as consultative, often imposing barriers in order to give efficient patient care and maintain efficient use of resources. In order that greatest use of the laboratory service can be achieved in the United Kingdom, guidelines relating to appropriate and effective laboratory investigation should be agreed between clinicians and laboratory specialists and further studies undertaken to characterise the effects on outcome measures such as patient bed-stay, of the availability of test data and consultant opinion. The strong tradition of mutual respect and understanding between the two disciplines should not be jeopardised by the view of the clinician, who has the responsibility of diagnosing and managing the patient, that the laboratories are there to provide a service. Improved communication, both verbal and electronic, is required to reposition laboratory services within a rapidly changing health service.

Chemistry, Clinical↗
PubMed1996

A new clinical laboratory information system architecture from the OpenLabs project offering advanced services for laboratory staff and users.

The OpenLabs project aims to improve the efficiency and effectiveness of clinical laboratory services by integrating decision support systems with laboratory information systems and equipment. Standards for electronic data interchange between laboratories and other medical systems using the EUCLIDES/OpenLabs coding scheme and an open architecture for clinical laboratory information systems have been specified. This article gives an account of the proposed architecture and outlines new software applications being developed using the architecture which provide advanced services for ordering and reporting of laboratory tests, advanced instrument workstation and laboratory management services, including an OpenLabs Service Manager application which co-ordinates the available services.

Chemistry, Clinical↗
PubMed1996

The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prolongation of the plasma half-life of IL-6.

Interleukin 6 (IL-6) is considered an important mediator of acute inflammatory responses. Moreover, IL-6 functions as a differentiation and growth factor of hematopoietic precursor cells, B cells, T cells, keratinocytes, neuronal cells, osteoclasts, and endothelial cells. IL-6 exhibits its action via a receptor complex consisting of a specific IL-6 receptor (IL-6R) and a signal transducing subunit (gp130). Soluble forms of both receptor components are generated by shedding and are found in patients with various diseases such as acquired immune deficiency syndrome, rheumatoid arthritis, and others. The function of the soluble (s)IL-6R in vivo is unknown. Since human (h)IL-6 acts on human and murine target cells, but murine IL-6 on murine cells only, we constructed transgenic mice expressing the hsIL-6R. We report here that in the presence of hsIL-6R, mice are hypersensitized towards hIL-6, mounting an acute phase protein gene induction at significantly lower IL-6 dosages compared to control animals. Furthermore, in hsIL-6R transgenic mice, the detected acute phase response persists for a longer period of time. The IL-6/IL-6R complex prolongs markedly the Il-6 plasma half-life. Our results reinforce the role of the hsIL-6R as an agonistic protein, help to understand the function of the hsIL-6R in vivo, and highlight the significance of the receptor in the induction of the acute phase response.

Acute-Phase Reaction↗
PubMed1996

Incorporation of the Arden Syntax within the reimplementation of a closed-loop decision support system.

The initial implementation of a clinical decision support system, although extremely successful and popular with users, suffered from response time and operational support difficulties. As part of the redesign of the system, which uses closed-loop rules to propose laboratory and other investigations, the decision was taken to move to Arden Syntax for the expression of such rules, although in some areas the current standard was felt to be either inadequate or inelegant. Such limitations have been overcome by the development of local extensions to the Arden Syntax, which are described and where appropriate proposed as possible enhancements of the standard. The use of common UNIX tools in the creation of a compiler which converts Arden Medical Logic Modules to M (MUMPS) code is also discussed.

Decision Making, Computer-Assisted↗
PubMed1996

Radiological method for preoperative determination of isometric attachment points of an anterior cruciate ligament graft.

The purpose of this study was to develop a radiological method which would be preoperatively available to help determine the best graft placement (with respect to isometricity as well as absence of graft impingement) for all knees. The radiological method is described in full detail. We also present the most significant experimental work supporting our development. Firstly, we studied the path followed by radio-opaque objects inserted in the mobile tibia around the fixed femur. Secondly, we compared the distances measured between selected femoral and tibial points radiologically (according to our method) and clinically (with a currently available isometer). The main results were: (1) every tibial point considered moves on an arc of a circle centered or a corresponding femoral point. We should then speak of pairs of isometric points instead of a single femoral isometric zone; (2) the more posterior the tibial point, the more anterior and distal the corresponding femoral point and vice versa; (3) the distance variations induced by rotation did not exceed 1.5 to 2.5 mm when measured either radiologically or clinically; (4) on the radiological and clinical measurements, the difference of length variations during flexion was also very small (mean 0.22 mm; SD 1.2 mm). We conclude that this very simple method allows us to find the femoral transition line for every knee (whatever its size, shape or dynamics). It aids preoperative planning in anterior cruciate ligament graft reconstruction.

Anterior Cruciate Ligament↗
PubMed1996

Linear estimation discriminates midline sources and a motor cortex contribution to the readiness potential.

Spatiotemporal dipole modelling of the generators of the readiness potential (RP) prior to voluntary movements has yielded diverging results concerning the contributions of supplementary motor area (SMA) and primary motor cortex. We applied an alternative approach (i.e. linear estimation theory) to measurements of the RP preceding fixed and freely selected finger movements, measured at 28 electrodes of the extended 10-20 system. The volume conductor properties of the head were modelled by 3 concentric spheres. Current densities were reconstructed on a spherical surface, placed at a depth of 5 mm from the inside of the skull. Lead field normalization was applied. The analysis shows activity on the midline as well as near the primary motor area. Although some features of the reconstructions are not readily interpretable, separate contributions of midline sources (including presumably SMA) and motor cortex to the RP are clearly distinguished.

Adult↗
PubMed1996

Studies on the cell tropism of Listeria monocytogenes in ovine fetal brain cell cultures.

The uptake of Listeria monocytogenes by cells in primary dissociated brain cell cultures prepared from ovine fetuses at approximately 50 to 60 days of gestation was studied using a sequential double immunofluorescence technique with antibodies against cell type-specific markers and the bacterial pathogen. Cell cultures were inoculated with bacteria at day 4, 8, and 15 in vitro. Listeria monocytogenes was predominately internalized by CD68-positive macrophages, followed by astrocytes, fibronectin-expressing cells, and neurons. An uptake of the bacterium by galactocerebroside (GC)-positive oligodendrocytes, which were first detected at day 15 in vitro, did not occur. Although a tropism for neurons was not observed, the susceptibility of neurons for infection with Listeria monocytogenes is in accordance with the supposed intraaxonal migration of the bacterium in the pathogenesis of focal brain stem encephalitis. The pattern of the infection rates of ovine brain cell types was similar to that shown in murine fetal brain cell cultures, indicating that there is no species-specific brain cell tropism of the bacterium.

Animals↗