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Biomedical subjects

R Lohmann

Publications and source records attributed to R Lohmann.

At least 37 records · Page 2Linked to original sources
PubMed1999

Rat liver endothelial cell glutamine transporter and glutaminase expression contrast with parenchymal cells.

Despite the central role of the liver in glutamine homeostasis in health and disease, little is known about the mechanism by which this amino acid is transported into sinusoidal endothelial cells, the second most abundant hepatic cell type. To address this issue, the transport of L-glutamine was functionally characterized in hepatic endothelial cells isolated from male rats. On the basis of functional analyses, including kinetics, cation substitution, and amino acid inhibition, it was determined that a Na+-dependent carrier distinct from system N in parenchymal cells, with properties of system ASC or B0, mediated the majority of glutamine transport in hepatic endothelial cells. These results were supported by Northern blot analyses that showed expression of the ATB0 transporter gene in endothelial but not parenchymal cells. Concurrently, it was determined that, whereas both cell types express glutamine synthetase, hepatic endothelial cells express the kidney-type glutaminase isozyme in contrast to the liver-type isozyme in parenchymal cells. This represents the first report of ATB0 and kidney-type glutaminase isozyme expression in the liver, observations that have implications for roles of specific cell types in hepatic glutamine homeostasis in health and disease.

Amino Acid Transport Systems, Basic↗
PubMed1999

[Psychogenic impairment and current feelings in the elderly. Which options are offered by the biographical perspective?].

In the Eldermen study funded by the German Research Association (DFG), a consecutive sample of patients, aged > or = 60 (n = 120) and being treated for a variety of internal medical complaints in an acute geriatric hospital were examined with the help of comprehensive somatic diagnostics, standardised questionnaires, and a semi-structured biographical interview. The study investigates the relationship between burdensome and supportive biographical experiences and the extent of psychogenic impairment as well as aspects of feeling tone and self-concept in later life. For the degree of psychogenic impairment (Impairment Score. IS; Schepank 1995), subjectively experienced burdens and support were found to be more relevant than "objective" burdens. As expected, subjective burdens consistently experienced over several life phases, particularly in association with limited experienced support, were found to be associated with greater psychogenic impairment and a higher "case risk" in later life. However, the patients with the highest values for current life satisfaction as well as a more positive self-concept were not those patients who never experienced more burdens than support in their biographies, but rather those who experienced more burden than support in one life phase. The results are presented in relation to models of learning theory and object relation theory and discussed for their clinical relevance.

Aged↗
PubMed1999

Preemptive therapy in CMV-antigen positive patients after liver transplantation--a prospective trial.

OBJECTIVE: Preemptive therapy with intravenous ganciclovir and CMV-hyperimmunoglobulin in asymptomatic CMV pp65-antigen positive patients was compared with treatment of only symptomatic CMV-disease after liver transplantation in an open prospective study. PATIENTS AND METHODS: 48 out of 200 liver transplant recipients became positive during six weeks follow-up after transplantation. 17 out of these 48 patients who were already symptomatic at the time of positive antigen testing were successfully treated with ganciclovir and CMV-hyperimmunoglobulin. 31 asymptomatic antigen-positive patients were randomised to receive preemptive therapy or to receive therapy only at onset of clinical symptoms. RESULTS: Only two out of 15 patients in this latter group without preemptive therapy developed CMV-syndrome and were successfully treated with intravenous ganciclovir. 13 patients did not experience any clinical symptoms or disease and were therefore spared unneccessary toxicity and costs. The overall incidence of CMV-infection and -disease in the whole study population of 200 liver transplant recipients was 25% and 10%. As expected, CMV-negative patients who received an organ from a seropositive donor were at a higher risk of CMV-infection and -disease, but did not show more severe infections clinically. Patients with IL-2 receptor antibody induction therapy seemed to have a higher risk for CMV-infection and -disease.

Adult↗
PubMed1998

Dioxins and furans in air and deposition: a review of levels, behaviour and processes.

This paper is a comprehensive, critical review of the levels, behaviour and processes affecting polychlorinated dibenzo-p-dioxins and -furans (PCDD/Fs) in air and deposition. Aspects of sampling, analysis and quality assurance/control are discussed initially, before a review of the PCDD/F concentrations in ambient air is presented. The general trend in sigma P4-8 CDD/F (and sigma TEQ) is: remote sites < 0.5 pg/m3 (sigma TEQ < 10 fg/m3); rural sites approximately 0.5-4 pg/m3 (sigma TEQ approximately 20-50 fg/m3); and urban/industrial sites approximately 10-100 pg/m3 (sigma TEQ approximately 100-400 fg/m3). The commonly held view that a consistent mixture of PCDD/Fs in air exists is evaluated and questioned. Issues of seasonality and short-term changes in air concentrations are also critically discussed, with respect to the possibility of seasonal emission sources to air and seasonally dependent loss processes. Data on the gas-particle partitioning of PCDD/Fs in air are reviewed; the limited database to date is believed to provide evidence for an exchangeable transfer of PCDD/Fs between these two phases. The potential importance of photolytic and radical reaction degradation processes and wet/dry deposition processes in modifying the mixture of PCDD/Fs in air is discussed. Some homologue/congener specific 'weathering' of the mixture of PCDD/Fs emitted to the atmosphere clearly occurs, but in general PCDD/Fs have 'long' atmospheric residence times, rendering them subject to long-range atmospheric transport. Data are reviewed which relate the mixture of PCDD/Fs in air to that in deposition; this leads to the conclusion that different homologue groups (which are partitioned differently between the gas and particulate phase) are transferred to the earth's surface with broadly similar efficiencies.

Air Pollutants↗
PubMed1998

Mapping of the ligand-selective domain of the Xenopus laevis corticotropin-releasing factor receptor 1: implications for the ligand-binding site.

The nonselective human corticotropin-releasing factor receptor 1 (hCRF-R1) and the ligand-selective Xenopus CRF-R1 (xCRF-R1) were compared. To understand the interactions of sauvagine and ovine CRF, both high-affinity ligands for hCRF-R1 but surprisingly weak ligands for xCRF-R1, chimeric receptors of hCRF-R1 and xCRF-R1 followed by double or multiple point mutations were constructed. Binding studies and cAMP assays demonstrated that the N-terminal domain exhibited the complete ligand selectivity of xCRF-R1. The important region was mapped between amino acids 70 and 89; replacement of amino acids Arg76, Asn81, Gly83, Leu88, and Ala89 in hCRF-R1 with the corresponding amino acids of xCRF-R1 (Gln76, Gly81, Val83, His88, and Leu89) resulted in a receptor that had approximately 30-fold higher affinity for human/rat CRF than for sauvagine. Mutagenesis of these amino acids in xCRF-R1 to the human sequence completely abolished the ligand selectivity of xCRF-R1. Mutagenesis of amino acids 88 and 89 in hCRF-R1 or xCRF-R1 had only a minor (approximately 2.5-fold) effect on the ligand selectivity of the mutant receptor. Substitution of Arg76, Asn81, and Gly83 in hCRF-R1 with the corresponding sequence of xCRF-R1 (Gln76, Gly81, and Val83) resulted in a receptor with approximately 11-fold higher affinity for human/rat CRF compared with ovine CRF or sauvagine. When only two of these three amino acids were mutated, no effect on the ligand selectivity was observed. On the basis of these data, it is suggested that amino acids 70-89 of CRF-R1 are important for the ligand binding site.

Amino Acid Sequence↗
PubMed1998

Stimulation of rat hepatic amino acid transport by burn injury.

Burn injury accelerates hepatic amino acid metabolism, but the role of transmembrane substrate delivery in this response has not been investigated. We therefore studied the effects of cutaneous scald injury on the Na+-dependent transport of glutamine and alanine in isolated rat liver plasma membrane vesicles. Scald injury resulted in liver damage and a 1.4- to 2.3-fold and 1.5- to 2.8-fold stimulation of hepatic transport rates for glutamine and alanine, respectively, proportional to the total burned surface area (TBSA) after 24 hours. Enhanced uptake of glutamine and alanine was attributable to increases in the maximum velocity (Vmax) of system N and system A activities, respectively. Hepatic amino acid transport activity remained elevated in vesicles from burned animals after 72 hours, but the degree of stimulation (1.3- to 1.7-fold for glutamine and 1.3- to 1.6-fold for alanine) was less than that observed 24 hours after thermal injury. Liver function tests returned to control values after 72 hours as well, indicating rectification of hepatic damage. In contrast to the induction of hepatic system A and system N activity in catabolic states such as cancer and endotoxemia, further studies showed that tumor necrosis factor (TNF) failed to play a significant role in burn-stimulated amino acid transport rates. When combined with plasma liver enzyme profiles, early transient hepatic amino acid transporter stimulation may support amino acid-dependent pathways involved in the repair of burn-dependent hepatic damage.

Amino Acids↗
PubMed1998

Pain, coping and psychological well-being in late life.

In the present article, the relationships between pain, coping, functional capacity and psychological well-being are examined in a population of older patients (>/=60 years; n=202) treated for a variety of somatic complaints in a university-affiliated hospital. Results indicate that moderate to extreme pain is common in older patients and often occurs in several body regions simultaneously. Extreme pain in one or more body regions is associated with reduced daily functional capacity, lower values for life satisfaction and self-evaluated competence, and more negative attitudes towards the present and future. Results of a hierarchical cluster analysis reveal interindividual differences in coping approaches among older patients suffering from extreme pain; they also emphasize the importance of cognitive strategies and life-review coping. Relevance for clinical practice with older pain patients is discussed.In the present article, the relationships between pain, coping, functional capacity and psychological well-being are examined in a population of older patients (>/=60 years; n=202) treated for a variety of somatic complaints in a university-affiliated hospital. Results indicate that moderate to extreme pain is common in older patients and often occurs in several body regions simultaneously. Extreme pain in one or more body regions is associated with reduced daily functional capacity, lower values for life satisfaction and self-evaluated competence, and more negative attitudes towards the present and future. Results of a hierarchical cluster analysis reveal interindividual differences in coping approaches among older patients suffering from extreme pain; they also emphasize the importance of cognitive strategies and life-review coping. Relevance for clinical practice with older pain patients is discussed. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗
PubMed1998

A randomized, placebo-controlled trial with anti-interleukin-2 receptor antibody for immunosuppressive induction therapy after liver transplantation.

The introduction of quadruple induction therapy after liver transplantation with the murine anti-interleukin-2 receptor (IL-2R) antibody (BT563) has decreased the incidence of serious side effects, such as tachycardia, hypertension, rash, fever and nausea since it does not lyse its target cell. To investigate the immunosuppressive efficacy of BT563, a placebo-controlled trial was performed and BT563 was added to the standard triple induction after liver transplantation. Forty consecutive recipients of primary orthotopic liver transplants (OLT) (median age 47 yr [range 18-65]) were randomized. All patients received triple immunosuppression with cyclosporine A (CyA), prednisolone (PRED) and azathioprine (AZA). In addition, 19 patients received BT563 (Biotest, Dreieich, Germany) at a dose of 10 mg/d from day 0 until day 12. The remaining 21 patients received a placebo infusion at the same days after transplantation. Minimal follow-up for all patients was 3 yr. Patient survival at 3 yr was 74% in the BT563 group and 90% in placebo group. Similar results were observed for graft survival. Two acute rejection episodes were detected in the BT563 group and 9 acute rejections (5 steroid-resistant) were observed in the placebo group (p < 0.034). The incidences of sepsis, pneumonia, cholangitis, urinary tract infections as well as cytomegalo-virus (CMV) infections were similar in both groups. Side effects of the BT563 therapy and/or post-transplant lymphoproliferative disease (PTLD) were not detected. Quadruple induction therapy with BT563 significantly reduces the incidence of rejection episodes after liver transplantation, while infectious complications and/or PTLD is not increased. Therefore, the anti-IL2 receptor antibody BT563 constitutes a safe and efficient addition to the immunosuppressive induction regimen following OLT.

Acute Disease↗
PubMed1997

A prospective randomized trial comparing interleukin-2 receptor antibody versus antithymocyte globulin as part of a quadruple immunosuppressive induction therapy following orthotopic liver transplantation.

BACKGROUND: Quadruple immunosuppressive induction therapy has been shown to markedly reduce the incidence of acute rejection episodes without increasing the incidence of infectious complications after liver transplantation. However, the use of polyclonal antibody preparations (e.g. antithymocyte globulin [ATG]) is associated with side effects such as fever and tachycardia. To evaluate the efficacy and the safety of a monoclonal antibody directed against the interleukin-2 receptor (BT563) in comparison with ATG as part of a quadruple induction regimen, a prospective, randomized study was conducted. METHODS: Eighty consecutive adult recipients of primary orthotopic liver transplants were randomized to receive either BT563 (10 mg/day; days 0-12; n=39) or ATG (5 mg/kg/day; days 0-6; n=41) in addition to the standard immunosuppressive protocol consisting of cyclosporine, and prednisolone, and azathioprine. RESULTS: Patients treated with BT563 had a significantly lower incidence of steroid-sensitive rejection episodes (3 vs. 11; P<0.025) and also significantly fewer drug-related side effects (4 vs. 18, P<0.038) when compared with patients treated with ATG. The incidence of infectious complications was not different between the two groups. Patient survival did not differ significantly between the two groups (84.6% at 1, 2, and 3 years in the BT563 group and 90.2% at 1 year and 87.8% at 2 and 3 years for the ATG group). Analysis of graft function showed an advantage for the BT563 group in terms of postoperative bilirubin levels. However, no differences were observed in long-term follow-up between the two groups. CONCLUSIONS: Our results indicate that treatment with anti-interleukin-2 receptor antibody as part of quadruple induction therapy after orthotopic liver transplantation is safe and effective and shows fewer steroid-sensitive rejection episodes as well as fewer side effects when compared with quadruple induction therapy including ATG.

Adult↗
PubMed1997

Induction of glutamine synthetase expression after major burn injury is tissue specific and temporally variable.

BACKGROUND: Major burn injury results in a translocation of amino acids from peripheral tissues to the abdominal viscera. Glutamine is a major participant in this event. Thermal injury causes a depletion of plasma and muscle glutamine pools as well as activation of proteolysis and release of glutamine from skeletal muscle. De novo synthesis of glutamine is regulated by the expression of the enzyme glutamine synthetase (GS). We studied the tissue-specific regulation of GS expression after thermal injury. METHODS: Burn injury of rats was produced by scalding of 25 or 40% of skin surface. In normal rats, four organs, including lung, muscle, kidney, and liver were assayed for relative GS messenger RNA content by Northern blotting 8 and 24 hours after 40% area burn. The effect of adrenalectomy on GS mRNA induction in muscle was assessed 24 hours after 25% area burn injury. RESULTS: GS mRNA levels were increased 2.3-fold in lung at 8 hours and 7.3-fold in muscle at 24 hours after burn injury. No appreciable increase in GS mRNA level was observed in kidney or liver. Muscle GS mRNA levels were lower than sham-operated controls in both burned and unburned adrenalectomized rats. However, adrenalectomy did not attenuate relative GS mRNA induction in muscle at 24 hours after burn injury. CONCLUSIONS: Burn injury causes an induction in GS mRNA levels in a tissue-specific fashion. Adrenalectomy greatly reduced GS mRNA levels, but did not completely block the induction of GS express in muscle after burn injury. This finding suggests that glucocorticoid hormones together with a unknown factor of nonadrenal origin influence this metabolic response to burn injury.

Adrenalectomy↗
PubMed1997

Biographical reconstruction of WWII experience: an exploration of German remembrance.

First results of the Eldermensch-Study (N = 50) indicate that German National Socialism and the historical events associated with World War II play a central role in the oral histories of older Germans. Six distinct patterns of late life cognitive appraisal of war-time experience: survival challenge (further divided into "active" and "passive" survivorship), passive benefit, opportunism, value verification, and acceptance despite hardship are presented and discussed as structural themes in the life story. These categories not only represent interindividual differences in the appraisal of war-time experience, but often reflect contrasting patterns of personal response to the social and political circumstances of this era of German history. In addition to cohort and gender differences, divergence in locus of control orientation as well as the role of social bonding and instrumental social support are discussed. Differences revealed in the biographical interviews are further reflected in the results of standardized questionnaires.

Adaptation, Psychological↗
PubMed1996

A prospective study of human herpesvirus type 6 detected by polymerase chain reaction after liver transplantation.

Human herpesvirus type 6 (HHV-6) causes roseola infantum (exanthema subitum) upon primary infection in young children. Thereafter it persists lifelong in the organism. Like other herpesviruses, HHV-6 can be reactivated in periods of immunosuppression - e.g., after organ transplantation. In order to study the incidence and the time to reactivation after orthotopic liver transplantation (OLT) we tested buffy coat lysates before and up to 10 weeks after transplantation for the presence of HHV-6 DNA by polymerase chain reaction (PCR). Forty-six patients (male n=27, female n=19) with a median age of 48 years (range 20-66) were studied. Altogether, 30 of 287 (10.5%) buffy coat samples were PCR-positive. Before OLT 2 of 21 (9.5%) patients were positive. This ratio is not different from healthy blood donor controls. After OLT 13 of 46 (23.8%) patients were positive on one or more occasions. However, there was no statistically significant difference before and after OLT. Ten patients were analyzed for HHV-6 variants by restriction enzyme digestion of PCR products. One patient carried variant A and 9 variant B. In conclusion, HHV-6 can be detected in buffy coat cells after OLT. Our observations do not argue in favor of a reactivation.

Adult↗
PubMed1996

Structure optimization of an artificial neural filter detecting membrane-spanning amino acid sequences.

An artificial neural network has been developed for the recognition and prediction of transmembrane regions in the amino acid sequences of human integral membrane proteins. It provides an additional prediction method besides the common hydrophobicity analysis by statistical means. Membrane/nonmembrane transition regions are predicted with 92% accuracy in both training and independent test data. The method used for the development of the neural filter is the algorithm of structure evolution. It subjects both the architecture and parameters of the system to a systematical optimization process and carries out local search in the respective structure and parameter spaces. The training technique of incomplete induction as part of the structure evolution provides for a comparatively general solution of the problem that is described by input-output relations only. Seven physiochemical side-chain properties were used to encode the amino acid sequences. It was found that geometric parameters like side-chain volume, bulkiness, or surface area are of minor importance. The properties polarity, refractivity, and hydrophobicity, however, turned out to support feature extraction. It is concluded that membrane transition regions in proteins are encoded in sequences as a characteristic feature based on the respective side-chain properties. The method of structure evolution is described in detail for this particular application and suggestions for further development of amino acid sequence filters are made.

Algorithms↗
PubMed1995

Comparison of polymerase chain reaction from plasma and buffy coat with antigen detection and occurrence of immunoglobulin M for the demonstration of cytomegalovirus infection after liver transplantation.

We compared the value of PCR on plasma with PCR on buffy coat leukocytes, Ag assay, and the determination of IgM antibodies by ELISA for the diagnosis and follow-up of cytomegalovirus infection. Thirty patients were followed after liver transplantation (LTX). We compared the tests to assess their clinical usefulness. Fourteen of 30 (46%) patients were both positive in plasma and buffy coat PCR and Ag test. Sixteen patients were negative in both procedures. There was a 97.2% concordance between PCRs done from plasma or buffy coat. The concordance of results of PCR and Ag test in single samples was 94.3%. Discordant results were found in 5.6% of samples. Discordance was observed in the early and the late phase of CMV infection and was due to positive PCRs preceding positive Ag tests for 1-3 weeks in one-half of the patients. IgM antibodies were first observed after a median period of 8 weeks (range, 6-11 weeks) after LTX. Positive PCRs and Ag tests preceded clinical manifestation of CMV disease by a 1 week median (range, 0-3 weeks), whereas positive IgM ELISAs occurred after a median period of 2.5 weeks (range, 0-4 weeks) after the onset of CMV disease. The sensitivity and specificity of both PCR and Ag test were identical, 100% and 76%, respectively. However, for the IgM ELISA, the sensitivity was only 66%, and the specificity was 84%. In conclusion, plasma or buffy coat PCR and Ag test are equally reliable procedures for early detection and monitoring of CMV infection. PCR can become positive earlier than the Ag test, but it is technically more demanding to perform. The demonstration of IgM antibodies is of little practical help because an antibody response occurs too late in relation to infection.

Adult↗