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Biomedical subjects

M Bauer

Publications and source records attributed to M Bauer.

At least 163 records · Page 9Linked to original sources
PubMed2001

Detection of human papillomavirus on Papanicolaou-stained cervical smears using indirect in situ polymerase chain reaction hybridization.

OBJECTIVE: Polymerase chain reaction (PCR) and indirect in situ hybridization were combined to detect human papillomavirus (HPV) DNA on Papanicolaou (PAP)-stained cervical smears. To our knowledge, this is the first report of an experiment using indirect in situ PCR (IS-PCR) on PAP-stained cervical smears. DESIGN: We collected native cell specimens from cervicovaginal lavage of 162 patients with squamous intraepithelial lesions. Solution-phase PCR (SP-PCR) was performed as the reference method in the detection of HPV DNA. Indirect IS-PCR was carried out for the same patients to detect the HPV DNA types 6/11 and 16/18 after the PAP-stained smears had been decolorized. Low-risk and high-risk HPV DNA types were also detected by both SP-PCR and indirect IS-PCR. RESULTS: In the evaluation by indirect IS-PCR, 48 of 81 PAP-stained cell smears of low-grade squamous intraepithelial lesions were positive for HPV DNA, as compared to 40 positive cell smears determined by indirect SP-PCR (sensitivity of indirect IS-PCR compared to SP-PCR, 98.1%). Forty-two of 42 high-grade squamous intraepithelial lesion samples were positive for HPV DNA, as determined by both methods (sensitivity of IS-PCR, 100%). Cell lines investigated in this study as positive or negative controls for HPV DNA were confirmed by indirect IS-PCR and SP-PCR. CONCLUSIONS: Our data show that in comparison to SP-PCR, indirect IS-PCR is a highly sensitive method to detect HPV DNA in cell smears from the uterine cervix. The advantages of indirect IS-PCR are (a) low numbers of cells needed, (b) the possibility of using PAP-stained specimens, and (c) cytologic details of smears can be preserved.

DNA, Viral↗
PubMed2001

Leucocyte proliferation in the bovine corpus luteum.

Leucocytes vary in type and number during the lifespan of a corpus luteum. The aim of this study was to determine whether there is an increase in the number of lymphocytes and macrophages as a result of local proliferation. Bovine corpora lutea were classified into stages of development, secretion and regression. A new double immunolabelling method was established for nuclear Ki-67 antigen (a marker for cell proliferation) and for leucocyte surface antigens (detection of CD2-, CD3-, CD4-, CD8-positive lymphocytes and CD14-positive monocytes). Differential cell counting was performed. Between the stages of development and regression there was an increase in the number of T-lymphocytes and macrophages. The percentage of proliferating leucocytes in relation to the total number of proliferating cells was approximately 20% at the stage of advanced secretion and 70% at late regression. The increase in the number of proliferating leucocytes at late regression was due to CD14-positive macrophages. These macrophages migrated from small blood vessels into the septa of corpora lutea at the early stage of regression. Macrophages showed local proliferation in the late stage of regression when capillaries were no longer present. It is concluded that the physiological involution of the corpus luteum is an inflammatory-like condition, which includes local proliferation of monocytes.

Animals↗
PubMed2001

Genetic and pharmacological analyses of involvement of Src-family, Syk and Btk tyrosine kinases in platelet shape change. Src-kinases mediate integrin alphaIIb beta3 inside-out signalling during shape change.

Platelet shape change was found to be associated with an increase in protein tyrosine phosphorylation upon stimulation of thrombin-, ADP- and thromboxane A2-G-protein coupled receptors in human platelets and thromboxane A2 receptors in mouse platelets. By using PP1 and PD173956, two structurally unrelated specific inhibitors of Src-family tyrosine kinases, and mouse platelets deficient in the Src-kinase Fyn or Lyn, we show that Src-family kinases cause the increase in protein tyrosine phosphorylation. We further detected that the non-Src tyrosine kinase Syk was activated during shape change in a manner dependent on Src-family kinaseactivation. The pharmacological experiments and the studies on Fyn-, Lyn- and Syk-deficient mouse platelets showed that neither Src-family kinases nor Syk are functionally involved in shape change. Also human platelets deficient of the tyrosine kinase Btk showed a normal shape change. Binding of PAC-1 that recognizes activated integrin alphaIIb beta3 complexes on the platelet surface was enhanced during shape change and blocked by inhibition of Src-kinases. We conclude that the activation of Src-kinases and the subsequent Syk stimulation upon activation of G-protein coupled receptors are not involved in the cytoskeletal changes underlying shape change of human and mouse platelets, but that the stimulation of this evolutionary conserved pathway leads to integrin alphaIIb beta3 exposure during shape change.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2001

Cost optimization in anaesthesia.

As a result of the progress which has been made in medicine and technology and the increase in morbidity associated this demographic development, the need and thus the costs for medical care have increased as well. The financial resources which are available for medical care, however, are still limited and hence the funds which are available must be distributed more efficiently. Cost optimisation measures can help make better use of the profitability reserves in hospitals. The authors show how costs can be optimised in the anaesthesiology department of a clinic. Pharmacoeconomic evaluation of the new inhalation anaesthetics shows an example of how the cost structures in anaesthesia can be made more obvious and potential ways savings be implemented. To reduce material and personnel costs, a more rational means of internal process management is presented. According to cost-effectiveness analysis, medications are not divided into the categories inexpensive and expensive but rather cost-effective or non-cost-effective. By selecting a cost-effective drug it is possible to reduce cost at a hospital. For example, sevoflurane at a fresh gas flow of below 3 l/min has been shown to be a cost-effective inhalation anaesthetic which, in terms of the economics, is also superior to intravenous anaesthesia with propofol. In addition to these measures of reducing material costs, other examples are given of how personnel costs can be reduced by optimising work procedures: e.g. effective operating theatre co-ordination, short switchover times by overlapping anaesthesia induction and the use of multifunctional personnel. The gain in productivity which is a result of these measures can positively affect profits, and by optimising the organisation of procedures to shorten the times required to carry out a procedure, costs can be reduced.

Anesthesia↗
PubMed2001

[Marfan syndrome and heart valve diseases].

Marfan syndrome is a hereditary disease of the connective tissue with increased mortality mostly due to changes of the cardiovascular system. We describe our experience with the surgical treatment of 243 patients with Marfan syndrome and cardiovascular complications. We report the results of treatment of annulo-aortal ectasia using the classical surgical methods of Bentall DeBono and Cabrol and the method for preservation of the native aortic valve and concomitant surgery of the mitral valve. Reconstruction or replacement of the mitral valve is mainly based on the classical indications. Preservation of the native aortic valve and reconstruction of the mitral valve in patients with Marfan syndrome is possible but the long-term results are still unknown.

Adolescent↗
PubMed2001

[Surgery in terminal mitral valve diseases].

In the past few years both the spectrum of mitral valve diseases leading to surgery and the surgical techniques have changed. We present our experience with the preservation of the subvalvular apparatus when mitral valve replacement is performed. In addition to preservation of the subvalvular apparatus of the posterior mitral leaflet, five techniques of subvalvular preservation are described. We conclude that mitral valve replacement should always aim at preservation of the subvalvular structures. The surgical method of choice in cases of isolated mitral valve insufficiency is mitral valve reconstruction. Treatment of associated atrial fibrillation, preferably by radiofrequency ablation, should always be performed concomitantly. Surgery of the mitral valve represents a palliative operation in selected patients with terminal cardiomyopathy.

Atrial Fibrillation↗
PubMed2000

Nonviral glial cell-derived neurotrophic factor gene transfer enhances survival of cultured dopaminergic neurons and improves their function after transplantation in a rat model of Parkinson's disease.

Transplantation of dopaminergic fetal mesencephalic tissue into the striatum is currently being developed for treatment of patients with advanced Parkinson's disease. Ethical concerns regarding the use of human fetal tissue, and the limited availability as well as poor survival and differentiation of dopaminergic neurons after transplantation have reduced the extent and outcome of this approach so far. With the purpose of finding means to increase the yield of dopaminergic neurons in transplants, and to reduce the amount of fetal tissue needed for each transplanted patient, we transfected rat fetal ventral mesencephalic (VM) tissue grown as organotypic free-floating roller tube (FFRT) cultures with a vector encoding human glial cell-derived neurotrophic factor (hGDNF). For transfer of an episomal expression vector (pRep7-GDNF8) a nonviral, nonliposomal cationic transfection technique was applied and optimized. Recombinant hGDNF expression resulted in a higher number of TH-positive neurons in the cultures as measured 6 days after transfection. Ventral mesencephalic cultures expressing hGDNF were then grafted into the striatum of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. Grafting of genetically modified VM cultures resulted in earlier functional recovery compared with grafting nontransfected cultures. We conclude that organotypic free-floating roller tube cultures can be successfully transfected to produce hGDNF with effects on TH-expressing neurons in vitro and functional effects after grafting in a rat Parkinson's disease model.

Animals↗
PubMed2000

Numerical chromosomal aberrations of chromosome 1 and 7 in dysplastic cervical smears.

Cervical smears with Papanicolaou's staining (PAP) reveal only morphological characteristics of epithelial cells of the cervix uteri. Since chromosomal aberrations are known to play a role in malignant transition, we analyzed cervical smears for numerical changes of the chromosomes 1 and 7 with fluorescence in-situ hybridization to probe for a diagnostic value of these chromosomes in the characterization of cervical dysplasia. Cervical smears were collected from 21 patients with suspect histology of curettage or biopsy specimen, 14 of them having been subsequently graded as cervical intraepithelial neoplasia (CIN) III and 5 as CIN II. Nineteen normal cervical smears (PAP I-II) served as controls. Smears were hybridized with chromosomal enumeration probes for chromosome 1 and 7. Disomic cells (2 copies of chromosome 1 and 7) were decreased in the CIN II (63%) and CIN III group (57%) with respect to the control group (77%). Cells with 3 signals for chromosome 7 were significantly more frequent in the CIN III and the CIN II group than in the control group (6.7, 6.4 and 0.7%, respectively). Only the CIN II group (10%), but not CIN II (6%), showed a significant trisomy for chromosome 1 as compared with the controls (3.8%). A close correlation between the incidence of trisomy 1 or 7 and PAP grading was observed. PAP III-IIID smears with high trisomy 1 counts corresponded to CIN III histology, while all CIN II patients were PAP III-IIID with low incidence of trisomy 1. We conclude that trisomy of chromosome 7 is a feature of cervical dysplasia and seems to be an early event in dysplastic transition. In contrast, trisomy of chromosome 1 is observed only in high grade dysplasia and may be a marker for pre-malignant lesions.

Cell Nucleus↗
PubMed2000

Mildly oxidized low density lipoprotein rapidly stimulates via activation of the lysophosphatidic acid receptor Src family and Syk tyrosine kinases and Ca2+ influx in human platelets.

In contrast to native low density lipoprotein (LDL), mildly oxidized LDL (mox-LDL) induced platelet shape change and stimulated during shape change the tyrosine phosphorylation of specific proteins including Syk; the translocation of Src, Fyn, and Syk to the cytoskeleton; and the increase of cytosolic Ca(2+) due to mainly Ca(2+) entry. The stimulation of these early signal pathways by mox-LDL was inhibited by desensitization of the lysophosphatidic acid (LPA) receptor and specific LPA receptor antagonists, was independent of the alpha(IIb)beta(3)-integrin, and was mimicked by LPA. Stimulation of tyrosine phosphorylation and Syk activation were independent of the increase of cytosolic Ca(2+) and were suppressed by genistein and two specific inhibitors of the Src family tyrosine kinases, PP1 and PD173956. In contrast to PP1 and PD 173956, genistein prevented shape change by mox-LDL. The results indicate that mox-LDL, through activation of the LPA receptor, stimulates two separate early signal pathways, (a) Src family and Syk tyrosine kinases, and (b) Ca(2+) entry. The activation of these early signaling pathways by mox-LDL probably plays a role in platelet responses subsequent to shape change. The inhibition of mox-LDL-induced platelet activation by LPA receptor antagonists or dietary isoflavonoids such as genistein could have implications in the prevention and therapy of cardiovascular diseases.

Blood Platelets↗
PubMed2000

Plasminogen activator inhibitor 1. Structure of the native serpin, comparison to its other conformers and implications for serpin inactivation.

The crystal structure of a constitutively active multiple site mutant of plasminogen activator inhibitor 1 (PAI-1) was determined and refined at a resolution of 2.7 A. The present structure comprises a dimer of two crystallographically independent PAI-1 molecules that pack by association of the residues P6 to P3 of the reactive centre loop of one molecule (A) with the edge of the main beta-sheet A of the other molecule (B).Thus, the reactive centre loop is ordered for molecule A by crystal packing forces, while for molecule B it is unconstrained by crystal packing contacts and is disordered. The overall structure of active PAI-1 is similar to the structures of other active inhibitory serpins exhibiting as the major secondary structural feature a five-stranded beta-sheet A and an intact proteinase-binding loop protruding from the one end of the elongated molecule. No preinsertion of the reactive centre loop is observed in this structure.A comparison of the present structure with the previously determined crystal structures of PAI-1 in its alternative conformations reveals that, upon cleavage of an intact form of PAI-1 or formation of latent PAI-1, the well-characterised rearrangements of the serpin secondary structural elements are accompanied by dramatic and partly unexpected conformational changes of helical and loop structures proximal to beta-sheet A. The present structure explains the stabilising effects of the mutated residues, reveals the structural cause for the observed spectroscopic differences between active and latent PAI-1, and provides new insights into possible mechanisms of stabilisation by its natural binding partner, vitronectin.

Amino Acid Sequence↗
PubMed2000

Cerebellar vermis area in schizophrenic patients - a post-mortem study.

Neuroimaging studies of cerebellar atrophy in schizophrenia have yielded contradictory results. In computer-tomography (CT) studies, cerebellar atrophy was found in up to 40% of schizophrenic patients. However, several recent magnetic resonance imaging (MRI) studies could not replicate these early findings; in addition, contradictory observations of enlargement of vermal structures were reported. In contrast to the number of CT and MRI studies, there are only a few neuropathological reports on this subject. In a post-mortem study we analyzed the midsagittal vermal area of formaldehyde-fixed cerebella of 12 deceased schizophrenic patients and 12 age- and gender-matched control subjects by using morphometrical methods. Statistical analysis using ANOVA revealed no significant group effects, but there were interactions with gender and cerebellar brain weight. In view of the present results, the common concept of cerebellar atrophy in schizophrenic patients appears premature. Gender effects and secondary processes (e.g., relevant alcohol or drug abuse) cannot be excluded as possible factors causing decrease of vermal areas in schizophrenic patients.

Adolescent↗
PubMed2000

HPV type 16 protein E7 HLA-A2 binding peptides are immunogenic but not processed and presented.

Human papillomaviruses (HPV) have been implicated in the etiology of cervical malignancies and a high percentage of cervical carcinoma cells express HPV-16 E6 and E7 oncoproteins. These proteins are attractive targets for cytolytic T lymphocyte (CTL) mediated immunotherapy. We screened peptides derived from the HPV-16 E7 protein for binding to HLA-A2 and tested their potential to induce specific CTL responses in chimeric HLA-A2/H2-Kb transgenic mice. From eight potential binding peptides four displayed binding and were tested for immunogenicity. CTL activity was tested using target cells pulsed with peptide or expressing E7 protein. While there was no CTL induction observed with the peptides 7-15, 66-74 and 82-90, CTL from mice immunized with 86-93 lysed targets presenting the peptide in the context of the HLA-A2/H2-Kb molecule or wild-type HLA-A2. In contrast, 86-93 induced CTL showed no cytolytic activity against cells expressing the protein E7 and vaccination with the E7 protein did not lead to cytotoxicity against targets pulsed with the 86-93 peptide. Therefore the peptide 86-93, which binds to HLA-A2, is able to induce CTL responses in context of HLA-A2, but the peptide appears not to be processed or presented by HPV type 16 infected cells.

Animals↗
PubMed2000

Differential remodeling of the left and right heart after norepinephrine treatment in rats: studies on cytokines and collagen.

Continuous intravenous infusion of norepinephrine norepinephrine (NE, 0.1 mg/kg/h) induced hypertrophy of the left ventricle (LV), but not of the right ventricle (RV) in rats, although RV systolic pressure (RVSP) was much more elevated than LVSP. After NE infusion, there was a time-dependent (20 min to 72 h) expression in the mRNA of interleukin (IL)-6 and IL-1 beta. The expression of IL-6 increased markedly and reached the maximum after 4 h with an 80-fold elevation. In the RV, the expression increased only 20-fold. The mRNA of IL-1 beta increased significantly after NE stimulation only in the LV and reached the maximum after 12 h with a 12-fold elevation. After 12 h of NE infusion, colligin mRNA was elevated for the first time with further progression until 72 h. The six-fold abundance of colligin mRNA seen after 72 h was significantly higher in the LV than in the RV. A similar increase was observed on the protein level (Western blotting). The expression of collagen I and III increased significantly after 24 h only in the LV. After 72 h, the mRNA expression of collagen I was increased 16-fold and that of collagen III 10-fold. This expression was significantly higher than that in the RV. Also the elevation in atrial natriuretic peptide (ANP) mRNA started earlier and was more pronounced in the LV than in the RV. The alpha- and beta-adrenergic receptor blocker carvedilol normalized all functional parameters after 6 h and 72 h and prevented the development of LV hypertrophy that occurred after 72 h. The NE-induced increased expression of the mRNAs studied was either prevented (IL-6, IL-1 beta ) or attenuated (colligin, collagen I and III, ANP) by combined alpha- and beta-receptor blockade. The elevation of afterload which was associated with the NE effect was normalized by the calcium-channel blocker nisoldipin, but NE-induced LV hypertrophy and the increase in ANP and collagen mRNA were not affected.

Adrenergic Antagonists↗
PubMed2000

[Time course of neuromuscular blockade after rocuronium. A comparison between women and men].

BACKGROUND: We studied 40 patients (20 female and 20 male) undergoing elective surgery under general anaesthesia to evaluate the effect of gender on the pharmacodynamics of rocuronium. METHODS: Using electromyography (EMG) we determined the maximal neuromuscular block and time course of action of 0.45 mg/kg rocuronium (1.5 x ED95). RESULTS: Age and body mass index were comparable between females and males (38 (+/- 8) vs. 37 (+/- 10) years and 24.2 (+/- 2.9) vs. 25.2 (+/- 1.7) kg/m2. However, significant differences in weight and height were found between females and males (65.7 +/- 9.3 kg vs. 77.5 +/- 5.5 kg; p < 0.01 and 178 +/- 6.8 cm vs. 164 +/- 6.7 cm; p < 0.01). Onset time was shorter in females (168 +/- 65 s vs. 211 +/- 56 s; p < 0.05). Maximal neuromuscular blockade after 0.45 mg/kg rocuronium was 94 (+/- 3) % in females and 89 (+/- 6) % in males; p < 0.01. Clinical duration was increased in females (23 +/- 5 min vs. 17 +/- 5 min; p < 0.05), while the recovery index was comparable between both groups (9 +/- 4 min in females and 9 +/- 3 min in males; n.s.). CONCLUSION: Compared to men neuromuscular blockade after 0.45 mg/kg rocuronium was more pronounced in women. The onset time was shortened and the clinical duration increased in female patients.

Adult↗
PubMed2000

[Mammography].

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Breast Diseases↗
PubMed2000

[Ventricular septal aneurysm in a patient with Marfan syndrome].

This is the first description of a patient with Marfan syndrome and an aneurysm of the ventricular septum. Apart from a borderline dilatation of the ascending aorta, there were no cardiovascular manifestations of Marfan syndrome. A transesophageal echocardiographic examination showed a large aneurysm of the ventricular septum. To prevent the imminent rupture and the acute occurrence of a significant left-to-right-shunt on the ventricular level, as well as increasing irritation of tricuspid valve, an elective operation was performed. Besides the routine cardiological diagnostics, the search for intracardial defects is also necessary in patients with Marfan syndrome.

Adult↗
PubMed2000

Impersonation of a ruptured thoracic aneurysm by a transdiaphragmatic pancreatic cyst.

Pancreatic cysts can, in rare cases, expand into the posterior mediastinum and may require surgical resection. We present the case of a patient with a thoracic aneurysm, in whom the mediastinal involvement of a chronic pancreatic cyst masqueraded as a ruptured aneurysm. Surgery was undertaken: first, the initial resection and drainage of the thoracic portion of the pseudocyst, and second, a thorough cleansing of the entire cyst through median laparotomy 15 days later.

Aged↗