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Biomedical subjects

M Bauer

Publications and source records attributed to M Bauer.

At least 307 records · Page 17Linked to original sources
PubMed1997

[Physiologic and pathologic patterns of reaction to silicone breast implants].

Local morphological reaction patterns on breast implants can be of high significance as possible starting point for controversely discussed systemic immune response triggered by silicon or silicone. Therefore, the collagenous capsules of 149 explanted mammoplasty prostheses were examined macroscopically, under a scanning electron microscope and light-microscopically using antibodies to the macrophage antigen CD68, vimentin, muscle actin, and the proliferation antigen MIB1, and were then correlated with anamnestic data (implanted type of prosthesis, indication for im- or explantation). According to our examinations, the in-vivo durability of the prostheses' shells is considerably decreasing with the expansion of their surfaces. Regardless of the type of the prostheses' surface regularly a chronic-proliferating inflammation pattern could be identified in the periprosthetic capsulectomy specimens starting with a synovial metaplasia of proliferating CD-68-negative and vimentin-positive mesenchymal cells in the area surrounding the implants and ending by its transformation into a stage of dense hyaline collagenous fibrous tissue after an advanced implantation period (> 2 years). By this, the texturing of the prosthesis surface modifies only the course, but not the quality of the chronically fibrosing inflammation. Bleeding of prosthesis as well as the incorporation of the polyurethane-foam coating of different prosthesis types into the periprosthetic breast capsule lead to a significant lymphoplasmacytic infiltration, partly with participation of local vessels as defined in a "silicone vasculitis". Morphological signs of an at least local immune response are detectable in 8.3% of the examined fibrotic capsules even without a morphologically identifiable foreign-body embedding. They can be possibly referred to- as well as the complete absence of hyaline collagenous fibrous tissue in 30% of the cases-a yet not causally clarified, inter-individually different susceptibility of the implant bearers. Only the systematic registration of the above-mentioned morphological reaction patterns in a "prosthesis-passport" together with the additional clinical observation of the patients can ensure in future the realistic estimation of potential health risks caused by silicone breast implants.

Actins↗
PubMed1997

[Effect of gamma-hydroxybutyric acid and pentoxifylline on kidney function parameters in coronary surgery interventions].

After cardiac surgery, transient renal dysfunction often occurs. The main reasons for impairment of renal function are intraoperative hypotension, ischemia/reperfusion injury and inflammatory response to cardiopulmonary bypass (CPB). Pentoxifylline is known to have anti-inflammatory properties. Gamma-hydroxybutyrate (GHB), an endogenous regulator of energy metabolism, showed beneficial effects on experimental intestinal ischemia/reperfusion injury and liver graft function. Both drugs may be of practical interest in diminishing renal damage during and after cardiac surgery. After approval by the ethics committee and informed consent, 45 patients for elective coronary artery bypass grafting with no clinical and laboratory impairment of renal function were randomized into 3 groups (15 patients each): group 1 received saline as control, group 2 received pentoxifylline intraoperatively (1 mg/kg/h after a priming dose of 1 mg/kg) and group 3 received GHB intraoperatively (25 mg/kg/h after a priming dose of 25 mg/kg) in a double-blinded fashion. During 3 periods (before CPB, from the beginning of CPB until the end of surgery, 24 hours postoperatively), glomerular (creatinine clearance, CCr) and tubular markers of renal function (beta-NAG, alpha 1-microglobulin) were detected in addition to clinical routine standards (creatinine, urea, fractional excretion of sodium). Changes in glomerular and in tubular function were comparable in all groups without characteristic effects of either GHB or pentoxifylline. With CPB, CCr decreased significantly until the end of operation, but showed a rise to preoperative levels on the first day after operation. Tubular function markers (beta-NAG, alpha 1-microglobulin, related to simultaneous excretion of creatinine) showed a remarkable rise after the beginning of CPB up to the postoperative period. The results of the present pilot study suggest the detection of tubular proteins and enzymes a useful addition to present routine clinical standards for recognizing early intraoperative changes in renal function. In the patients studied, there were no clinical signs of renal dysfunction. Neither GHB nor pentoxifylline--in the doses applied--was able to show a therapeutic benefit despite the theoretical advantages.

Aged↗
PubMed1997

[The Gretchen question: acquittal after infanticide in denied pregnancy?].

A mentally healthy woman killed her newborn directly after parturition. The physical and mental factors of pregnancy were continuously concealed, and even the menses persisted for nine months. Psychiatric expert opinion certified a psychologically exceptional state of mind of the woman, and the court acquitted her.

Adult↗
PubMed1997

C-erbB-2 amplification and expression in gestational trophoblastic disease correlates with DNA content and karyotype.

The subject of this retrospective study was to evaluate the potential benefit of the c-erbB-2 oncogene amplification and expression in 27 complete hydatidiform moles as well as in 9 cases of persistent gestational trophoblastic disease defined by elevated serum beta-human choriongonadotropin. The persistent cases were histopathologically classified as 5 complete hydatidiform moles, 3 invasive moles and 1 choriocarcinoma. In addition, we determined the DNA content and the karyotype of the sex chromosomes. The data were correlated with the histopathologic characteristics of gestational trophoblastic diseases. Cases with c-erbB-2 amplification and expression in combination with DNA hyperploidy showed higher proliferation and a more aggressive behavior (2 complete hydatidiform moles with lung and liver metastases, 2 invasive moles and 1 choriocarcinoma). XY karyotype was evident in the choriocarcinoma and in two complete hydatidiform moles with advanced stage and DNA hyperploidy.

DNA↗
PubMed1996

A chondroitin/dermatan sulfate form of CD44 is a receptor for collagen XIV (undulin).

Collagen XIV, a fibril-associated collagen with interrupted triple helices, is expressed in differentiated soft connective tissues and in cartilage. However, a cellular receptor for this protein has not been identified. Here we show that human placental collagen XIV, isolated by a mild and simple two-step method, serves as adhesive protein for a variety of mesenchymal and some epithelial cells. Cell adhesion could be inhibited by preincubation of the collagen XIV substrate with heparin or with the chondroitin/dermatan sulfate proteoglycan decorin and by pretreatment of cells with chondroitinase ABC or heparinase III, suggesting a cell membrane proteoglycan as receptor. Affinity chromatography of 125I-labeled fibroblast cell surface proteins on collagen XIV-Sepharose yielded a chondroitin/dermatan sulfate proteoglycan with a molecular mass of 97-105 kDa after chondroitinase ABC digestion and of 60-70 kDa after further treatment with N-glycosidase F. The eluates contained also some high-molecular-weight material that was susceptible to digestion with heparinase but no detectable integrins. Immunoprecipitation with a specific monoclonal antibody identified the prominent chondroitin/dermatan sulfate proteoglycan as a member of the CD44 family. The interaction between collagen XIV and cells appears to be finely tuned, since matrix-associated glycosaminoglycans, and particularly proteoglycans like decorin, could compete with cells for the binding site(s) on collagen XIV under physiological conditions.

Cell Adhesion↗
PubMed1996

Dynamics of viral variants in HIV-1 Nef and specific cytotoxic T lymphocytes in vivo.

The vigorous CTL response directed against HIV is considered to be important in reducing HIV viral load, although it is unable to stop ongoing viral replication, which generates new antigenic variants. We analyzed the impact of sequential changes in five epitopes of HIV-1 Nef on CTL recognition in four stable patients. A high rate of variation was found, and in all these patients we could detect CTL specific for 32 out of 36 autologous viral variants occurring in 5 HLA-A2- or HLA-B7-restricted Nef epitopes at two time points. Two distinct patterns for dynamics of CTL responses to viral variation were observed: 1) temporary amplification of viral variants followed by expansion of variant-specific CTL, ultimately leading to the disappearance of 12 out of the 14 initial epitope variants within two years. A second set of viral variants that had replaced the initial ones could also stimulate specific CTL precursors in the context of the same or an alternative HLA molecule; and 2) persistence of 2 viral variants in relatively conserved epitopes despite specific CTL recognition. Therefore, a remarkable flexibility of the immune system allows constant adaptation of CTL to multiple HIV variants and thus elimination of HIV variant-producing cells in slow progressors.

Amino Acid Sequence↗
PubMed1996

The 2.3 A crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator.

Tissue-type plasminogen activator (t-PA), a multidomainal serine proteinase of the trypsin-family, catalyses the rate-limiting step in fibrinolysis, the activation of plasminogen to the fibrin-degrading proteinase plasmin. Trigonal crystals have been obtained of the recombinant catalytic domain of human-two-chain t-PA, consisting of a 17 residue A chain and the 252 residue B chain. Its X-ray crystal structure has been solved applying Patterson and isomorphous replacement methods, and has been crystallographically refined to an R-value of 0.184 at 2.3 A resolution. The chain fold, active-site geometry and Ile276-Asp477 salt bridge are similar to that observed for trypsin. A few surface-located insertion loops differ significantly, however. The disulfide bridge Cys315-Cys384, practically unique to the plasminogen activators, is incorporated without drastic conformational changes as the insertion loop preceding Cys384 makes a bulge on the molecular surface. The unique basic insertion loop Lys296-Arg304 flanking the primed subsites, which has been shown to be of importance for PAI-1 binding and for fibrin specificity, is partially disordered; it can therefore freely adapt to proteins docking to the active site. The S1 pocket of t-PA is almost identical to that of trypsin, whereas the S2 site is considerably reduced in size by the imposing Tyr368 side-chain, in agreement with the measured preference for P1 Arg and P2 Gly residues. The neighbouring S3-S4 hydrophobic groove is mainly hydrophobic in nature. The structure of the proteinase domain of two-chain t-PA suggests that the formation of a salt bridge between Lys429 and Asp477 may contribute to the unusually high catalytic activity of single-chain t-PA, thus stabilizing the catalytically active conformation without unmasking the Ile276 amino terminus. Modeling studies show that the covalently bound kringle 2 domain in full-length t-PA could interact with an extended hydrophobic groove in the catalytic domain; in such a docking geometry its "lysine binding site" and the "fibrin binding patch" of the catalytic domain are in close proximity.

Amino Acid Sequence↗
PubMed1996

Crystallographic evidence that the F2 kringle catalytic domain linker of prothrombin does not cover the fibrinogen recognition exosite.

The 2.6-A x-ray crystal structure of bovine alpha-thrombin in complex with rhodniin, a protein inhibitor isolated from the bug Rhodnius prolixus, has been solved and refined. The structure has enabled us to trace the N-terminal part of the 49-residue A-chain of bovine alpha-thrombin for the first time, which is fixed in a U-shaped loop on the molecular surface opposite the active site canyon. Model building shows that the 25 amino acid residues that link the A-chain and F2 kringle cannot run through the fibrinogen recognition exosite. This demonstrates that this fibrinogen recognition exosite is available in prothrombin and meizothrombin.

Amino Acid Sequence↗
PubMed1996

Platelet-activating factor is involved in the regulation of pathological leukocyte adhesion after liver transplantation.

An increased leukocyte adhesion and loss of integrity of endothelial cells is known to be a critical step in the reperfusion period after cold ischemia of transplanted livers. Platelet-activating factor (PAF) is discussed as one of the inflammatory mediators involved in mediating reperfusion injury, e.g., by regulation of leukocyte adhesion. In this study we investigated the effect of a synthetic PAF receptor antagonist, WEB 2086 (Boehringer Ingelheim, FRG), on microcirculation and adhesion of leukocytes to sinusoidal endothelium after liver transplantation in the rat. Livers from SPRD rats (n = 6 per group) were stored for 5 hr in ice-cold UW solution and orthotopically transplanted using the cuff technique. In a randomized and blinded fashion WEB 2086 (1 mg/kg body wt) or placebo was given twice intravenously, at the beginning of the recipient operation and 1 min prior to reperfusion of the liver graft. After in vivo staining of leukocytes with acridine orange, microcirculation and leukocyte-endothelium interaction of transplanted livers and livers from sham-operated animals were investigated 90 min and 5 hr after surgery by means of intravital microscopy. After 90 min of reperfusion, temporary leukocyte adhesion in periportal regions was increased after liver transplantation (22.0 +/- 2.5%; mean +/- SEM) in contrast to the sham group (14.2 +/- 1.8%). Administration of WEB 2086 reduced temporary leukocyte adhesion significantly (11.5 +/- 2.5%; P < 0.05), whereas no significant differences were observed with respect to permanent leukocyte adhesion. Five hours after recipient operation, a significant increase of permanent leukocyte adhesion was observed after transplantation (21.0 +/- 2.6%; P < 0.05) compared to sham-operated animals (12.1 +/- 1.7%). Application of WEB 2086 diminished permanent leukocyte adhesion significantly (12.2 +/- 1.3%; P < 0.05), whereas no differences were noticed between the different groups with respect to temporary leukocyte adhesion at this time. The results indicate that reduction of temporary leukocyte adhesion in the early reperfusion period by administration of PAF receptor antagonist WEB 2086 was followed by a reduction of permanent leukocyte adhesion in the late reperfusion period, e.g., at 5 hr. Thus, it is concluded that PAF is one of the mediators which is involved in the regulation of leukocyte adhesion after liver transplantation.

Animals↗
PubMed1996

Giant cell tumour of the mandibular condyle.

The authors report a case of giant cell tumour of the mandibular condyle, which is a rare finding. This tumour, studied using the main three radiological modalities (plain radiography, CT and MRI) showed characteristic radiological features of "giant cell tumour".

Adult↗
PubMed1996

[The physiopathology of sepsis. Current concepts].

Clinical manifestations of sepsis, such as systemic inflammatory response and multiple organ dysfunction syndrome, are considered to be the results of a decompensated host defense response. If tissue injury is sufficiently severe to overwhelm local defense mechanisms, systemic activation of these essentially protective mechanisms may lead to autodestructive "host defense failure disease." This is not always caused by invading bacteria; sterile inflammation such as results from multiple trauma or pancreatitis can initiate a similar response. Evidence suggests that the activation of the macrophage/monocyte system that underlies the systemic inflammatory response may reflect one facet of a more generalized dysregulation of intercellular communication, as well as a dysfunction of such subcellular processes as signal transduction or stress gene expression. Alterations in signal transduction or stress gene expression can affect the host defense response to subsequent stressful events in either a negative or a positive sense. In particular, the sequential induction of acute phase and heat shock response may initiate programmed cell death, reflecting a potential molecular mechanism for the development of multiple organ dysfunction syndrome. The development of anti-inflammatory treatment strategies seems to be hampered by the discrepancy between locally protective and systemically detrimental properties of the host defense response.

Humans↗
PubMed1996

Nerve cell loss in the thalamic centromedian-parafascicular complex in patients with Huntington's disease.

The centromedian-parafascicular complex represents a nodal point in the neuronal loop comprising striatum--globulus pallidus--thalamus--striatum. Striatal neurone degeneration is a hallmark in Huntington's disease and we were interested in estimating total neurone and glial number in this thalamic nuclear complex. Serial 500-microns-thick gallocyanin-stained frontal sections of the left hemisphere from six cases of Huntington's disease patients (three females, three males) and six age- and sex-matched controls were investigated applying Cavalieri's principle and the optical disector. Mean neurone number in the controls was 646,952 +/- 129,668 cells versus 291,763 +/- 60,122 in Huntington's disease patients (Mann-Whitney U-test, P < 0.001). Total glial cell number (astrocytes, oligodendrocytes, microglia, and unclassifiable glial profiles) was higher in controls with 9,544,191 +/- 3,028,944 versus 6,961,989 +/- 2,241,543 in Huntington's disease patients (Mann-Whitney U-test, P < 0.021). Considerable increase of fibrous astroglia within the centromedian-parafascicular complex could be observed after Gallyas' impregnation. Most probably this cell type enhanced the numerical ratio between glial number and neurone number (glial index: Huntington's disease patients = 24.4 +/- 8.1; controls = 15.0 +/- 5.2; Mann-Whitney U-test, P < 0.013). The neurone number in the centromedian-parafascicular complex correlated negatively, although statistically not significantly, with the striatal neurone number. This lack of correlation between an 80% neuronal loss in the striatum and a 55% neurone loss in the centromedian-parafascicular complex points to viable neuronal circuits connecting the centromedian-parafascicular complex with cortical and subcortical regions that are less affected in Huntington's disease.

Adult↗
PubMed1996

The incidence of depression in new users of beta-blockers and selected antihypertensives.

We studied the occurrence of depression in new users of propranolol (n = 704), other beta-blockers (n = 587), angiotensin-converting enzyme inhibitors (n = 976), calcium channel blockers (n = 742), and diuretics (n = 773) in the Harvard Community Health Plan population. The period of the study was from April 1988 to June 1991. All study subjects were followed for new or newly recurrent depression for up to 6 months after receiving their first study prescription. Case status was confirmed by blinded medical record review. We found 10 cases of depression that met DSM-III-R criteria ("major depression") and an additional 18 cases that had one or more symptoms consistent with depression ("minor depression"). Rates of major depression in users of beta-blockers and users of non-beta-blocker study drugs were 5.8 per 1000 person-years of exposure and 9.6 per 1000 person-years, respectively. None of the cases of major depression was propranolol associated. Rates of major or minor depression (combined) in users of beta-blockers and users of non-beta-blockers were 20.2 per 1000 person-years and 25.2 per 1000 person-years, respectively. The age- and sex-adjusted relative risk of major or minor depression associated with the use of beta-blockers compared to non-beta-blockers was 0.8 (95% CI, 0.3-1.9). The relative risk associated with propranolol compared to non-beta-blockers was also 0.8 (95% CI, 0.1-2.7). Therefore, depression occurred no more frequently in beta-blocker users than in other members of the study base.

Adrenergic beta-Antagonists↗
PubMed1996

[Treatment of post-traumatic stress disorder].

PTSD is a frequent subject of empirical psychiatric research. There is, however, little knowledge about the efficacy of treatment methods. In this review, general therapeutic guidelines and common components of different psychotherapies are described. Approaches of behaviour, cognitive, psychodynamic and hypnotherapy are outlined. Controlled studies show the reduction of intrusive PTSD-symptoms in behaviour therapy. Effects of psychodynamic therapy on avoidance symptoms have been demonstrated in one study. Family and group therapy are described, their efficacy has not been empirically tested yet. The need to integrate different concepts and models is emphasized. Special guidelines in the treatment of victims of political persecution are summarized. In pharmacotherapy positive effects on partial PTSD-symptoms has been shown in particular for SSRI-antidepressants. Pharmacotherapy may be a useful addition to psychotherapy. Fixed guidelines for the treatment of PTSD can not be set up yet.

Combined Modality Therapy↗
PubMed1996

Human immune response to HIV-1 Nef. II. Induction of HIV-1/HIV-2 Nef cross-reactive cytotoxic T lymphocytes in peripheral blood lymphocytes of non-infected healthy individuals.

HIV-specific CD8+ cytotoxic T lymphocytes (CTL) are thought to have a beneficial role in HIV infection. In a previous report we have shown that HIV-1 Nef-specific CTL can be readily induced in peripheral blood lymphocytes of seronegative healthy young adults by in vitro stimulation with autologous Epstein-Barr virus-transformed B lymphoblastoid cell lines transfected with the HIV-1 nef gene. Here we demonstrate that these Nef-specific CTL can efficiently lyse HIV-infected primary CD4+ T lymphocytes. CTL of the blood donor tested were Nef-specific and restricted by the autologous MHC class I molecules HLA-A2 and HLA-B7. They recognized HIV-1 Nef in association with both restriction elements but HIV-2 Nef only in association with HLA-B7. The cross-reactivity of the induced effector cells together with the potent immunogenicity of Nef in healthy seronegatives further support the inclusion of Nef as a constituent of HIV vaccines.

B-Lymphocytes↗
PubMed1996

Ytterbium- and dysprosium-EOB-DTPA. A new prototype of liver-specific contrast agents for computed tomography.

RATIONALE AND OBJECTIVES: A series of studies was conducted to determine whether metal complexes of the EOB-DTPA type are useful as contrast agents for computed tomography (CT). METHODS: Metal complexes using EOB-DTPA as ligand were synthesized with lanthanide metal ions (lanthanum [La], cerium [Ce], praseodyme [Pr], gadolinium [Gd], dysprosium [Dy], ytterbium [Yb], and lutetium [Lu]) and with nonlanthanides (lead [Pb] and bismuth [Bi]). Complex stability was assessed by measuring binding to bone meal. The physicochemical parameters partition coefficient, osmolality, viscosity, and protein binding were determined in vitro. Tolerability was tested both in vitro (thromboplastin time, effect on erythrocytes) and in vivo (acute, neural, and cardiovascular toxicities). Biliary excretion and tissue distribution, especially liver, kidney, and bone concentrations, were measured in rats after intravenous doses of 0.5 mmol/kg. Imaging performance using CT was investigated in vitro in a phantom model and, for Gd-EOB-DTPA, in vivo by injecting doses of 0.5 mmol/kg into healthy or tumor-bearing rats and rabbits. RESULTS: The kinetic stability of M-EOB-DTPA complexes differed widely. Nonlanthanide metals, especially Pb-EOB-DTPA, provided less stable complexes than lanthanides with an optimum of stability for the metals Gd, Dy, Yb, and Lu. Tolerability was good for all compounds, best results were obtained for Gd and Yb. Concentrations in rat liver after administration of Gd-EOB-DTPA, 0.5 mmol/kg intravenous, were approximately 1 mumol/g, resulting in CT enhancement of 16 Hounsfield units (HU). Tumor tissue was not enhanced. In rabbits, at the same dose level 30 HU was found. CONCLUSIONS: Metal complexes of the EOB-DTPA type, especially those of Gd and Yb seem to be useful as iodine-free liver-specific contrast agents for CT.

Animals↗