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Biomedical subjects

U Lehmann

Publications and source records attributed to U Lehmann.

At least 19 recordsLinked to original sources
PubMed2006

Autophagy delays apoptotic death in breast cancer cells following DNA damage.

Early signaling in camptothecin-treated MCF-7 cells followed an intrinsic pathway, but death was delayed and late events exhibited few hallmarks of apoptosis. BH3-only proteins, such as Noxa, Puma and BimEL, were activated and localized to mitochondrial sites within 24 h following drug exposure. However, caspase activity was low and death was unaffected by caspase inhibition. Transmission electron micrographs showed the presence of large vacuoles in drug-treated cells. An autophagic survival response has been attributed to MCF-7 cells following nutrient starvation or exposure to tamoxifen. Here, we show that autophagy also plays an important role in the delayed DNA damage response. Confocal microscopy revealed colocalization of mitochondria with large autophagic vacuoles and inhibitors of autophagy increased mitochondrial depolarization and caspase-9 activity, and accelerated cell death. Furthermore, downregulation of autophagy proteins, Beclin 1 and Atg7, unmasked a caspase-dependent, apoptotic response to DNA damage. We propose that a post-mitochondrial caspase cascade is delayed as a result of early disposal of damaged mitochondria within autophagosomes. Our data also suggest that the use of autophagy as a means of delaying apoptosis or prolonging survival may be characteristic of noninvasive breast tumor cells. These studies underscore a potential role for autophagy inhibitors in combination with conventional chemotherapeutic drugs in early breast cancer therapy.

Apoptosis↗
PubMed2006

[Late secondary syphilis with ulceration of the tongue during HIV coinfection: case report].

With the continuing rise of syphilis incidence, late stages and atypical courses with HIV-coinfection can be expected. A 45 year old HIV infected male presented with an unusual manifestation of late secondary syphilis on the tongue, which was first diagnosed as a squamous cell carcinoma but cleared after therapy with penicillin. He also exhibited psoriasiform and annular lesions on the trunk and hyperkeratotic papules on the palms of the hand and soles of the feet. A TPHA test was negative due to a prozone phenomenon. With this case, we would like to emphasize the formerly well known relationship between the lesions of tertiary syphilis on the tongue and development of secondary carcinoma.

Anti-Bacterial Agents↗
PubMed2006

[Hepatocellular adenoma. Malignancy potential and differentiation from hepatocellular carcinoma].

In contrast to hepatocellular carcinoma (HCC), very few molecular pathological studies have been carried out on hepatocellular adenoma (HCA). Particularly from the surgical point of view, based on views passed on verbally and in the literature of the 1970s and 1980s, a possible degeneration of the HCA provides grounds for operating. Published cases of transitions from HCA into HCC were evaluated on the basis of today's morphological standards. A comparison was made between the patterns of new molecular pathological studies of HCA, above all the work of our own groups, and those of HCC. The results speak against the suggestion that a typical solitary HCA in pre-menopausal women is a precursor lesion of HCC. After a critical review of the literature, only one casuistic case of a transition of HCA to HCC under a hormone therapy, which is no longer practiced today, remained. A limitation of particular HCA in genetic and metabolic diseases, children, adult males, adenomatosis, and HCA-like tumors with known risk factors of HCC would seem pragmatically meaningful. With classic HCA, however, the oncological indication for surgery does not apply. A prerequisite is a histological clarification, if necessary with the support of molecular pathological methods.

Adenoma↗
PubMed2005

Compartment-specific quantitative gene expression analysis after laser microdissection from archival renal allograft biopsies.

BACKGROUND: Various immunological and non-immunological pathomechanisms are responsible for the cellular damage in renal allografts. Since the kidney is an anatomically complex organ with functional and morphological heterogeneous compartments (interstitium, tubuli, vessels, glomeruli), the local response to injury maybe variable, therefore, the identification of local pathomechanisms is important. AIM: To elucidate any discrepancies in quantitative mRNA expression profiles between a total specimen analysis and a cell-specific evaluation after laser microdissection. METHODS: Real-time RT-PCR was performed for complement component C3 and heme oxygenase-1 (HO-1) genes compared to the housekeeping gene beta-actin using whole section RNA extracted from formalin-fixed and paraffin-embedded archival material of 16 explanted, rejected renal allografts. Ten non-transplant nephrectomies served as controls. For five cases from each group, five different compartments of the organs (interstitium, proximal tubuli, distal tubuli, vessels, glomeruli) were microdissected and quantitative analysis for C3 and HO-1 was performed identically. RESULTS: Whole section mRNA expression analysis: the data showed a constant expression of the housekeeping gene beta-actin, a 7-fold increased expression of C3 and a 3-fold decreased expression of HO-1 in the allograft group as compared to the control group. mRNA expression results from microdissected compartments: in the control group, C3 and HO-1 expression could only be detected in the proximal tubuli of all cases whereas all five compartments analyzed from the rejecting kidneys showed expression of the two genes. In the allografts, expression levels of the investigated genes varied considerably not only among the different compartments but between individual cases as well. CONCLUSION: Laser microdissection combined with real-time RT-PCR is a feasible approach for retrospective quantitative gene expression analysis in formalin-fixed and paraffin-embedded renal allograft specimens. As shown for C3 and HO-1, cell-specific expression patterns ofpathogenetically relevant genes vary considerably between individual cases. A close correlation of morphology and cell-specific gene expression analysis will contribute to the elucidation of the complex pathogenesis of chronic renal allograft nephropathy.

Actins↗
PubMed2004

New method for time-resolved diesel engine exhaust particle mass measurement.

The Dekati mass monitor (DMM; Dekati Ltd., Finland), a relatively new real-time mass measurement instrument, was investigated in this project. In contrast to the existing gravimetric filter method also used as a standard for regulation purposes, this instrument provides second-by-second data on mass concentration in the engine exhaust gas. The principle of the DMM is based on particle charging, inertial and electrical size classification, and electrical detection of aerosol particles. This study focuses on the instrument's practical performance. Details on calibration and the theory of operation will be published elsewhere. The exhaust emissions of two heavy-duty engines complying with the Euro III emission standard were measured on a dynamic engine test bench. We looked atthe particle number and mass emissions of the engines in different transient test cycles and steady-state conditions. The ability to follow transient test cycles and the response times of the DMM were investigated. The aerosol mass concentration measured by the DMM was compared with the mass concentration obtained by the standard gravimetric filter method with Teflon-coated glass fiber filters. The total mass concentration (integral over the whole cycle) measured by the DMM is about 20% higher than that measured by the standard gravimetric filter method. The total mass concentration from the DMM was also compared with the volume concentration calculated from the electrical low-pressure impactor (ELPI) measurements. Correlations were made with other particle measuring systems. The DMM correlates very well with the particulate mass (R2 = 0.95) and exhibits good linearity and repeatability. The response time to a well-defined change in exhaust concentration was observed to be fast and stable. The DMM was able to follow transient test cycles and provides good results on a second-by-second basis. The instrument used in this study was still under development, and there is therefore no complete scientific background reference for the DMM. This study therefore focuses more on the measurements than on the scientific background. The measurements have shown thatthe DMM is an adequate instrument for measuring the mass concentration of engine exhaust, with results comparable to those from the standard gravimetric filter method. In addition, the DMM provides real-time second-by-second data of the mass concentration during transient test cycles.

Environmental Monitoring↗
PubMed2004

[Epigenetic changes in breast cancer shown by aberrant promoter methylation].

The aberrant methylation of cytosine residues in the promoter region of growth-regulatory genes is now recognized as an important inactivation mechanism in addition to deletion and mutation in the development and progression of cancer. Principally all pathways regulating proliferation and differentiation, which are perturbed in cancer cells, can be affected. In breast cancer epigenetic inactivation is a frequent and early event displaying great quantitative gene-specific differences during progression. The occurrence of specific aberrant methylation patterns is associated with the histological grade and subtype of mammary carcinoma biopsies.

Breast Neoplasms↗
PubMed2004

Capacity development through reflective practice and collaborative research among clinic supervisors in rural South Africa--a case study.

UNLABELLED: This article provides an example of one form of action research, collaborative enquiry, in the health sector. It argues that collaborative inquiry is a powerful tool to develop reflective capacity among health workers and can facilitate the ownership of learning and the production of usable knowledge. It reports the results of a research project investigating the roles and functions of clinic supervisors in three districts in the Eastern Cape Province, South Africa. BACKGROUND: Clinics are the cornerstone of the new district-based health system. They are staffed primarily by nurses and are often the only contact point for large parts of the rural population. In conditions of remoteness and isolation, clinic staff depend upon personal interaction with clinic supervisors to enable them to function productively. Yet experience has shown that supervisors do not always fulfil this role. This project aimed at gaining insight into the status of clinic supervision, understanding the factors that hinder effective supervision and making recommendations for improvements. METHODOLOGY: Using a participative approach of Collaborative Inquiry, a team of 10 clinic supervisors and the research co-ordinator collected data reflecting on their own practice over a period of 5 months. These data were then jointly analysed and written up. CONCLUSIONS: The participating clinic supervisors went through several periods of uncertainty, when many of them asked themselves why they agreed to this project. However, the engagement with stakeholders and colleagues and the joint analysis of research data soon proved to be a valuable source of insight. There was unanimity in the end that the research process had been very valuable and enabling.

Ambulatory Care Facilities↗
PubMed2003

[New aspects for minimally invasive interventions in orthopedic trauma surgery].

The minimally invasive method has gained complete acceptance for the treatment of diaphyseal fractures. In the majority of cases, this procedure is combined with stabilization of the fracture with insertion of an intramedullary implant. In cases of metaphyseal fracture, use of minimally invasive techniques depends on the extent of simultaneous involvement of the articular surface. For joint fractures, the main goal is anatomic reconstruction. At the same time as these less invasive surgical procedures and markedly improved methods of visualization have evolved, the implants themselves have also advanced. The standard implant of the future for plate osteosynthesis will be the interlocking plate. Minimally invasive surgical techniques will certainly continue to gather ground in the future for the entire field of accident surgery. Reduction of the surgical approach means less postoperative pain for the patient, earlier mobilization, and shortening of hospital stay and the whole process of rehabilitation.

Diagnostic Imaging↗
PubMed2003

Aberrant methylation and impaired expression of the p15(INK4b) cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML).

The important cell cycle regulatory gene p15(INK4b) has been shown to be inactivated in acute myeloid leukemia and myelodysplastic syndrome. Little is known about the expression and epigenetic modification of this gene in chronic myelomonocytic leukemia (CMML) that belongs to the myelodysplastic/myeloproliferative disorders (MDS/MPD) with a high proportion of blastic transformation. Analysis of bone marrow trephines in a series of 33 CMML cases showed an aberrant p15(INK4b) gene methylation in up to 58% of cases. Methylation was analyzed employing different methylation-specific PCR and genomic sequencing protocols. It turned out to be spread over a broad area of the 5' region and exhibited substantial heterogeneity between cases and even in individual patients. The degree of aberrant methylation was correlated with a reduced mRNA as well as reduced protein expression, and was associated with a higher expression of DNA methyltransferase DNMT 3A. We conclude that aberrant gene methylation is a frequent event in CMML that might contribute to the pathogenesis of this MDS/MPD.

Bone Marrow↗
PubMed2003

[Open reduction and internal fixation of unstable sacral fractures].

Sacral fractures are frequently misdiagnosed or overlooked, as the majority of the patients are suffering from polytrauma situations. Obvious clinical signs both of the fracture and the associated neurological complications are missing. A poor longterm outcome with pain and urogenital disorders is frequent. Based on clinical and biomechanical studies a new concept for internal fixation of transsacral pelvic instabilities combined with decompression of the central canal is applied. To approach the sacrum, a posterior longitudinal incision is carried out and can be modified according to the fracture pattern. Decompression and anatomic reduction is performed and the fracture stabilized with minimized small fragment implants which are solely fixed in the sacrum. 32 patients were treated according to this protocol between 1989 and 1996. Bony healing occurred in all but one case. A complete anatomical sacral reconstruction was achieved in 80 % of the cases, another 16 % had close to anatomic (< 5 mm) reconstruction. In eight cases a primary neurologic deficit was present, with five complete or partial recoveries directly postoperative. Complications occurred in seven patients with two secondary displacements.

Adolescent↗
PubMed2002

Influence of resistant starch on the SCFA production and cell counts of butyrate-producing Eubacterium spp. in the human intestine.

AIMS: The genus Eubacterium, which is the second most common genus in the human intestine, includes several known butyrate producers. We hypothesized that Eubacterium species play a role in the intestinal butyrate production and are inducible by resistant starch. METHODS AND RESULTS: In a human pilot study species-specific and group-specific 16S rRNA-targeted, Cy3 (indocarbocyanine)-labelled oligonucleotide probes were used to quantify butyrogenic species of the genera Eubacterium, Clostridium and Ruminococcus. Following the intake of RS type III a significant increase in faecal butyrate but not in total SCFA was observed. However, increase in butyrate was not accompanied by a proliferation in the targeted bacteria. CONCLUSIONS: The tested Eubacterium species have the capacity to produce butyrate but do not appear to play a major role for butyric acid production in the human intestine. SIGNIFICANCE AND IMPACT OF THE STUDY: In view of the fact that the bacteria responsible for butyrate production are largely unknown, it is still difficult to devise a dietary intervention to stimulate butyrogenic bacteria in a targeted way.

Acetates↗
PubMed2001

Real-time PCR analysis of DNA and RNA extracted from formalin-fixed and paraffin-embedded biopsies.

The archives of departments of pathology represent a unique source of morphologically defined biopsies derived from normal and pathologically altered tissues for which extensive clinical data are available. The exact quantification of nucleic acids in these biopsies offers a promising extension of current methodology to study the pathogenesis of many different diseases. The development of real-time PCR technology has greatly facilitated the realization of nucleic acid quantification. Now it is feasible to analyze large series of samples for the exact quantification of nucleic acids even if the number of target molecules is small and the amount of material available for analysis is limiting. This review focuses on our own experiences concerning the extraction of nucleic acids from fixed and embedded biopsies using both conventional approaches and laser-assisted microdissection and the subsequent application of real-time PCR methods for quantification of mRNA transcripts, gene copy number, and the methylation status. We provide a number of protocols to assist in the application of these techniques.

Biopsy↗
PubMed2001

[Multiple trauma with craniocerebral trauma. Early definitive surgical management of long bone fractures?].

Head injuries are found in 17.6% of all trauma in-patients and are the most common cause of death after injury (26.6%) in Germany. Main factors for the initial and follow up assessment are the Glasgow Coma Scale (GCS) and pupil reaction. These are of a very predictive value for the outcome and are essential for the emergency crew to choose the adequat trauma hospital. Secondary transport to a higher level trauma center is affected by additional risk factors and a delay in diagnosis resp. treatment. This will increase mortality and must be strictly avoided. Sufficient oxygenation and circulation prevent the patient from secondary brain damage. A low GCS (< or = 8 p.) or specific additional injuries are an indication for immediate intubation. The outcome in patients with a systolic blood pressure below 90 mmHg on arrival is worse: The longer the time of correction the lower the rate of survival. After resuscitation early fracture treatment depends on hemoglobin concentration, hemostasis, oxygenation, body temperature, injury pattern and on the initial cranial CT scan. Cerebral swelling, seen or expected, is a contraindication for definitive fracture stabilization. After resuscitation reassessment should be done including a second CT scan. Cerebral monitoring is best performed by continuous measuring of the intracranial and the arterial pressure. Their difference determines the cerebral perfusion pressure which should be 60 mmHg at least. Intracranial pressure rates below 20 mmHg are favourable. Optimal management within the first days is essential for good outcome.

Adolescent↗
PubMed2001

Demonstration of light chain restricted clonal B-lymphoid infiltrates in archival bone marrow trephines by quantitative real-time polymerase chain reaction.

Assessment of clonality either by demonstrating light chain restriction or showing monoclonal immunoglobulin gene rearrangement is a valuable and indispensable adjunct to diagnosis in hematopathology. The study of light chain restriction by immunohistochemistry on archival material is hampered by a very low sensitivity especially regarding low grade lymphomas of B cell origin. DNA rearrangement studies of the immunoglobulin locus do improve sensitivity markedly but for lymphomas of follicle center origin they are prone to false negative results due to hypermutations. Therefore we developed a new clonality assay based on the quantification of immunoglobulin light chain transcripts using real-time polymerase chain reaction technology, which is also suitable for the analysis of archival bone marrow trephines. We tested the reproducibility and sensitivity of this approach by comparatively analyzing a series of bone marrow trephines with multiple myeloma (n = 26), reactive lymphoid hyperplasia (n = 37), and focal infiltration by low grade B cell lymphoma (n = 29). We could raise the detection rate of clonality from an average of 17% by immunohistochemistry and 66% as assessed by polymerase chain reaction rearrangement studies to 83% by this new technique. Despite false negative results due to light chain hypermutation in some cases, the detection rate of clonality could be improved even for B cell lymphomas of follicle center origin (follicular lymphoma or marginal zone lymphoma) thus making this novel approach a valuable additional tool for the hematopathologist.

B-Lymphocytes↗
PubMed2001

[Bone screw osteosynthesis of medial femoral neck fracture in elderly patients].

This study evaluated the complication rate and surgical outcome following cannulated screw fixation of femoral neck fractures in elderly patients. Between 1.6.97 and 31.12.98 we operated on 110 patients with 112 fractures. The mean age was 78.4 years (range 25-96 years). Mean follow up was 6.8 months (range 3-16 months). The mortality rate was 22.7% (25/110). 60 patients with 61 fractures could be evaluated for complications, reoperations, pain and walking ability. 68.9% of the fractures healed. Avascular necrosis developed in 18%. Non-union rate was 8.2% and redislocation rate 4.9%. 18 patients needed a second operation, two thirds received an arthroplasty and one third had implant removal or replacement. In 81.6% of the patients (the patients with secondary arthroplasty excluded) pain relief was good. Insufficient reduction and malposition of the screws are the most common causes for failure of cannulated screw fixation of femoral neck fractures in the elderly.

Adult↗