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Biomedical subjects

M Peters

Publications and source records attributed to M Peters.

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

Possible role of human interleukin-6 and soluble interleukin-6 receptor in hepatitis B virus infection.

Human interleukin-6 has been shown to promote hepatitis B virus (HBV) infection. However, it is not clear whether this influence is the result of a direct interaction between interleukin-6 (IL-6) and the HBV envelope proteins or of a rather indirect mechanism. A direct interaction of IL-6 and the preS region of the large envelope protein (L-protein) of HBV has been reported. In this study we assessed the binding of IL-6 and of the IL-6 receptor subunits to the preS region of the L-protein of HBV. Binding of IL-6 and IL-6 receptor subunits sIL-6R and gp130 to preS was assessed by immunoprecipitation with recombinant preS proteins. In patient sera IL-6 and sIL-6R concentrations were analysed with respect to the course of hepatitis B infection during and after interferon-alpha (IFN-alpha) therapy. The IL-6 and IL-6 receptor subunits could not be precipitated with recombinant preS proteins. In sera of patients who responded to IFN-alpha therapy by virus elimination, a significant increase in sIL-6R concentration was measured. No increase in sIL-6R levels was seen in patients who did not respond to IFN-alpha. Hence, IL-6 and IL-6 receptor subunits do not bind to preS directly. A possible role for sIL-6R in the elimination of HBV infection is discussed.

Animals↗
PubMed2001

[Skelefon framework concept for defence against risks in unusual epidemics: steps by public health offices].

Necessary anti-epidemic measures have to be promulgated or taken immediately in case of a suspected case of pneumonic plague or a viral haemorrhagic fever which can be transmitted from human to human. A live threatening highly contagious infectious disease may occur at any place in Germany. Therefore each health office should have the relevant information on the available infrastructure in Germany concerning treatment and competence centres, diagnostic laboratories, dispatch of samples and patient transportation. They should also be able to give qualified recommendations to physicians and hospitals concerning the necessary measures in such a case. Contacts at risk have to be notified. Based on a risk assessment and the special living conditions of the contact person they should decide if and which further measures have to be initiated, especially in the case of post-exposure prophylaxis, separation and prohibition of work. In general, imported cases of dangerous infectious diseases quickly find the interest of the media, including all the implications resulting from this. A well-organized cooperation with the media and public relations helps to avoid unnecessary irritations and panic.

Communicable Disease Control↗
PubMed2001

Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands.

OBJECTIVE: To study the incidence, signs and symptoms, diagnostic tests, risk factors, therapy, and complications of pediatric venous thromboembolism (VTE) in The Netherlands. METHODS: A prospective 2-year registry of VTE in children aged < or = 18 years. RESULTS: Ninety-nine patients were registered. The annual incidence of VTE was 0.14/10,000 children, 35% of whom were symptom free. Almost half of the patients were newborns. Neonatal VTE was almost exclusively catheter related, located in the upper venous system, and asymptomatic. In older children VTE was catheter related in approximately one third and more often was located in the lower venous system. In 85% of all patients, thrombosis developed while the patient was in the hospital. Diagnosis was usually made by ultrasonography. In 98% of all patients, at least 1 risk factor was present. Congenital prothrombotic disorders were more often present in older children (21%) than in neonates (6%). A variety of treatment modalities were used. Morbidity consisted of bleeding (7%) and recurrent thrombosis (7%). Two children died as result of VTE. CONCLUSION: VTE is mostly diagnosed in hospitalized children, especially sick newborns with central venous catheters and older children with a combination of risk factors. Primary prevention, optimal treatment, and long-term outcome of pediatric symptomatic and asymptomatic VTE need to be studied.

Adolescent↗
PubMed2001

Mastoparan alters subcellular distribution of profilin and remodels F-actin cytoskeleton in cells of maize root apices.

Indirect immunofluorescence localization of profilin in cells of maize root apices revealed that this abundant protein was present both in the cytoplasm and within nuclei. Nucleo-cytoplasmic partitioning of profilin exhibits tissue-specific and developmental features. Mastoparan-mediated activation of heterotrimeric G-proteins, presumably through triggering a phosphoinositide-signaling pathway based on phosphatidylinositol-4,5-bisphosphate (PIP(2)), induced relocalization of profilin from nuclei into the cytoplasm of root apex cells. In contrast, PIP(2) accumulated within nuclei of mastoparan-treated root cells. Intriguingly, cytoplasmic accumulation of profilin was associated with remodeling of F-actin arrays in root apex cells. Specifically, dense F-actin networks were dismantled and distinct actin patches became associated with the periphery of small vacuoles. On the other hand, disruption of F-actin with the G-actin sequestering agent latrunculin B does not affect the subcellular distribution of profilin or PIP(2). These data suggest that nuclear profilin can mediate a stimulus-response action on the actin cytoskeleton which is somehow linked to a phosphoinositide-signaling cascade.

Actins↗
PubMed2001

Occurrence of pulmonary thromboembolism immediately after arthroplasty.

INTRODUCTION: Respiratory complications are common after arthroplasty, with pulmonary thromboembolic disease (PTE) and fat emboli being the most serious. A scintigraphic study was designed to assess the occurrence of both diseases. A prospective tomographic study of perfusion was performed within 24 h of arthroplasty. Details of the detection of fat embolism will be presented elsewhere. METHODS: Patients with previous PTE were excluded. Tomographic lung studies were acquired after 99mTc-macroaggregated albumin injection. Pre- and post-operative arterial blood gases (ABGs) and relevant chest radiography/computed tomography scans were obtained. ABGs were analysed as the difference in alveolar-arterial oxygen gradients, pre- and post-operatively (DA-a). RESULTS: Forty patients were studied (16F, 24M) with a mean age of 71 years (range 36-88 years). Of these, 16 were hip and 24 knee arthroplasties. PTE was detected in 25 of 38 (66%) patients evaluated. The value of DA-a was significantly different between patients with PTE and without PTE (P>0.05). Administration of prophylactic pre-operative low molecular weight heparin makes no difference to the early onset of PTE. CONCLUSION: There is a high incidence of PTE immediately after arthroplasty.

Arthroplasty, Replacement, Hip↗
PubMed2001

Monitoring the fetal heart non-invasively: a review of methods.

Doppler ultrasound, ultrasound M-mode analysis, fetal electrocardiography, and fetal magnetocardiography are methods by which the fetal heart can be monitored non-invasively. In this paper, they are evaluated and compared. Customarily, it is solely the fetal heart rate, which is monitored using the Doppler ultrasound technique since it is both simple to use and cheap. However, this method inherently produces an averaged heart rate and therefore cannot give the beat-to-beat variability. Fetal electrocardiography has similar advantages, but in addition offers the potential for monitoring beat-to-beat variability and performing electrocardiogram morphological analysis. Its disadvantage is that its reliability is only 60%, although it is the only technique that offers truly long-term ambulatory monitoring. Ultrasound M-mode analysis allows a estimation of atrial and ventricular coordination, as well as an estimation of PR intervals. Bradycardias, supraventricular tachycardias, extra systoles are readily diagnosed using this method although timing will be inaccurate. Fetal magnetocardiograms can be detected reliably and used for accurate beat-to-beat measurements and morphological analysis. Consequently, they can be used for the classification of arrhythmias and the diagnosis of a long QT syndrome and some congenital heart diseases.

Electrocardiography↗
PubMed2001

[Case report: Yersinia enterocolitica septicemia in an American minipig].

A natural, lethal enteritis and septicaemia caused by Yersinia enterocolitica in an American Minipig piglet is reported. The isolated strain was identified as serotype O:3 and biotype 4. Pathomorphological examination of the animal revealed a severe fibrinonecrotic ileitis and typhlocolitis. Pyogranulomatous lesions were detected in regional lymph nodes and several organs.

Animals↗
PubMed2001

Pathogenetic role of cyclooxygenase-2 in hyperprostaglandin E syndrome/antenatal Bartter syndrome: therapeutic use of the cyclooxygenase-2 inhibitor nimesulide.

Patients with hyperprostaglandin E syndrome/antenatal Bartter syndrome typically have renal salt wasting, hypercalciuria with nephrocalcinosis, and secondary hyperaldosteronism. Antenatally, these patients have fetal polyuria, leading to polyhydramnios and premature birth. Hyperprostaglandin E syndrome/antenatal Bartter syndrome is accompanied by a pathologically elevated synthesis of prostaglandin E(2), thought to be responsible for aggravation of clinical symptoms such as salt and water loss, vomiting, diarrhea, and failure to thrive. In this study administration of the cyclooxygenase-2 (COX-2) specific inhibitor nimesulide to patients with hyperprostaglandin E syndrome/antenatal Bartter syndrome blocked renal prostaglandin E(2) formation and relieved the key parameters hyperprostaglandinuria, secondary hyperaldosteronism, and hypercalciuria. Partial suppression of serum thromboxane B(2) synthesis resulting from platelet COX-1 activity and complete inhibition of urinary 6-keto-prostaglandin F(1alpha), reflecting endothelial COX-2 activity, indicate preferential inhibition of COX-2 by nimesulide. Amelioration of the clinical symptoms by use of nimesulide indicates that COX-2 may play an important pathogenetic role in hyperprostaglandin E syndrome/antenatal Bartter syndrome. Moreover, on the basis of our data we postulate that COX-2-derived prostaglandin E(2) is an important mediator for stimulation of the renin-angiotensin-aldosterone system in the kidney.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Cytokine production in unmedicated and treated schizophrenic patients.

Recent findings have strengthened the hypothesis that immunological dysfunctions may contribute towards the multifactorial pathogenesis of schizophrenia. The validity of these findings is questioned by the fact that most studied subjects have received potentially immunomodulatory medication upon investigation. In order to rule out such confounding effects, 24 initially unmedicated acutely ill schizophrenic patients were studied immunologically and psychiatrically (PANSS) before and during 4 weeks of neuroleptic treatment. The production of IFN-gamma was decreased upon admission and after 2 weeks of treatment compared to matched healthy controls. No differences in IL-2 and IFN-gamma production between unmedicated and medicated states were observed. These results do not support the notion that neuroleptic medication in vivo might influence TH1 cytokine production in schizophrenia.

Antipsychotic Agents↗
PubMed2000

The conserved PI3'K/PTEN/Akt signaling pathway regulates both cell size and survival in Drosophila.

Akt (or PKB) is an oncogene involved in the regulation of cell survival. Akt is regulated by phosphatidylinositol 3-OH kinase (PI3'K) signaling and has shown to be hyperactivated through the loss of the PTEN tumor suppressor. In Drosophila, insulin signaling as studied using the Drosophila IRS-4 homolog (Chico) has been shown to be a crucial regulator of cell size. We have studied Drosophila Akt (Dakt1) and have shown that it is also involved in the regulation of cell size. Furthermore we have performed genetic epistasis tests to demonstrate that in Drosophila, PI3'K, PTEN and Akt comprise a signaling cassette that is utilized during multiple stages of development. In addition, we show that this signaling cassette is also involved in the regulation of cell survival during embryogenesis. This study therefore establishes the evolutionary conservation of this signaling pathway in Drosophila. Oncogene (2000) 19, 3971 - 3977.

Animals↗
PubMed2000

Molecular analysis of human anti-factor VIII antibodies by V gene phage display identifies a new epitope in the acidic region following the A2 domain.

One of the major binding sites for factor VIII inhibitors is located within the A2 domain. In this study, phage display technology was used to isolate 2 human monoclonal antibodies, termed VK34 and VK41, directed toward the heavy chain of factor VIII. The V(H) domain of a single-chain variable domain antibody fragment (scFv) VK34 is encoded by germline gene segment DP-10. Epitope-mapping studies revealed that scFv VK34 is directed against amino acid residues Arg(484)-Ile(508), a previously identified binding site for factor VIII inhibitors in the A2 domain. ScFv VK34 inhibited factor VIII activity with a titer of 280 BU/mg. The V(H) domain of VK41 was encoded by germline gene segment DP-47. A phage corresponding to VK41 competed with a monoclonal antibody for binding to amino acid residues Asp(712)-Ala(736) in the acidic region adjacent to the A2 domain. Reactivity of VK41 with a factor VIII variant in which we replaced amino acid residues Asp(712)-Ala(736) for the corresponding region of heparin cofactor II was strongly reduced. In addition, substitution of Tyr(718719723) for Phe abrogated binding of VK41 to factor VIII. ScFv VK41 did not inhibit factor VIII activity. This study not only defines the primary structure of human anti-factor VIII antibodies reactive with the A2 domain, it also describes an antibody with an epitope not previously identified in the antibody repertoire of hemophilia patients with an inhibitor. (Blood. 2000;96:540-545)

Amino Acid Sequence↗
PubMed2000

Expression of IL-6 in the ischemic penumbra.

We examined the expression of IL-6 within the ischemic penumbra at various time points after transient (3 h) middle cerebral occlusion (MCA-O) in rats. The animals were killed at 1, 3, 7 or 14 days following operation. Coronal brain sections were processed for immunohistochemistry with antibodies against GFAP, OX 42, IL-6 and Nissl-staining. Glial activation within the penumbra started on day one after ischemia and persisted up to day 14. Expression of IL-6 was not present in sham-operated controls. One day after MCA-O there were several IL-6-positive cells in the penumbra. This expression of IL-6 increased on day 3 and remained elevated up to day 14. According to the shape of the IL-6-positive cells they seem to be microglia and neurons. The present results demonstrate a longlasting expression of IL-6 in the ischemic penumbra.

Animals↗
PubMed2000

Implementation of rules based computerised bedside prescribing and administration: intervention study.

OBJECTIVES: To implement and assess a rules based computerised prescribing system with the aim of improving the safety of prescriptions and the administration of drugs. DESIGN: Analysis of performance of computerised system plus questionnaire survey of users. SETTING: 64 bed renal unit in a teaching hospital. INTERVENTION: : Introduction of the system into routine clinical use. MAIN OUTCOME MEASURES: Number of attempted prescriptions cancelled by the system; proportion of warning messages overridden; users' comparisons of the system with conventional procedures. RESULTS: Between October 1998 and August 1999 the system cancelled 58 (0.07%) out of 87 789 prescriptions on the grounds of clinical safety. In addition, 427 (57%) attempted prescriptions generating high level warnings and 1257 (8%) generating low level warnings were not completed. In a user survey 82% (31/38) of doctors and nurses considered the system to be an improvement on conventional procedures. CONCLUSIONS: The system has contributed to safety and patient care. All prescriptions are complete and legible, and transcription errors have been eliminated. The system assists clinicians when they are writing a prescription by making available information on patients. The system supports clinical decision making and has been well received by doctors, nurses, and pharmacists.

Drug Therapy, Computer-Assisted↗
PubMed2000

[Blind spots of the diagnostic hemostasis screen].

The most powerful instrument to establish the presence or absence of a coagulation disorder is the history of the patient. In addition, screening laboratory tests (consisting of the platelet count, bleeding time and global clotting assays, such as the prothrombin time and the activated partial thromboplastin time) may be helpful to support the diagnosis. In two patients, a 21-year-old man and a 10-year-old girl, with a marked history of enhanced bleeding normal screening laboratory tests were found. The male patient had a congenital alpha 2-antiplasmin deficiency and the girl had a homozygous deficiency of factor XIII. Some defects in the coagulation system (such as defects in fibrin network formation and fibrinolysis, but also mild Von Willebrand disease) are indeed not detected by screening laboratory tests. In patients with a strong suspicion of a coagulation disorder such defects should be specifically tested for.

Adult↗
PubMed2000

Human antibodies with specificity for the C2 domain of factor VIII are derived from VH1 germline genes.

A serious complication in hemophilia care is the development of factor VIII (FVIII) neutralizing antibodies (inhibitors). The authors used V gene phage display technology to define human anti-FVIII antibodies at the molecular level. The IgG4-specific, variable, heavy-chain gene repertoire of a patient with acquired hemophilia was combined with a nonimmune, variable, light-chain gene repertoire for display as single-chain variable domain antibody fragments (scFv) on filamentous phage. ScFv were selected by 4 rounds of panning on immobilized FVIII light chain. Sequence analysis revealed that isolated scFv were characterized by V(H) domains encoded by germline genes DP-10, DP-14, and DP-88, all belonging to the V(H)1 gene family. All clones displayed extensive hypermutation and were characterized by unusually long CDR3 sequences of 20 to 23 amino acids. Immunoprecipitation revealed that all scFv examined bound to the C2 domain of FVIII. Furthermore, isolated scFv competed with an inhibitory murine monoclonal antibody for binding to the C2 domain. Even though scFv bound FVIII with high affinity, they did not inhibit FVIII activity. Interestingly, the addition of scFv diminished the inhibitory potential of patient-derived antibodies with C2 domain specificity. These results suggest that the epitope of a significant portion of anti-C2 domain antibodies overlaps with that of the scFv isolated in this study. (Blood. 2000;95:558-563)

Adult↗