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Biomedical subjects

P Obrist

Publications and source records attributed to P Obrist.

At least 37 records · Page 2Linked to original sources
PubMed2001

Elevated plasma levels of crosslinked fibrinogen gamma-chain dimer indicate cancer-related fibrin deposition and fibrinolysis.

Cancer-related fibrin deposition and fibrinolysis were investigated by two-dimensional gel electrophoresis of human solid tumor and effusion specimen in addition to plasma samples. Fibrinogen gamma-chain dimer indicating fibrin deposition and plasmin-generated fibrinogen beta-chain fragments were identified in various solid tumor types by amino acid sequencing, mass spectrometry analysis and Western blotting. In tumor-associated effusions, these techniques allowed to observe plasmin-generated fragments of fibrinogen alpha, beta and gamma-chains in addition to elevated levels of acute-phase proteins. Similar observations were made in case of inflammation-associated effusions. No fibrin degradation product was observed in plasma samples, however, high amounts of fibrinogen gamma-chain dimer crosslinked by transglutaminase were detected in plasma from tumor patients, but not in plasma from controls and patients suffering acute infections and/or inflammations. This finding demonstrated that high transglutaminase activity may be associated with cancer. The presented data indicate that the amount of crosslinked fibrinogen gamma-chain dimer in plasma may correlate with tumor-associated fibrin deposition. The tumor-biological relevance of this potential marker protein is discussed.

Biomarkers, Tumor↗
PubMed2000

Ep-CAM overexpression in breast cancer as a predictor of survival.

The epithelial glycoprotein Ep-CAM is overexpressed in colon cancer and breast cancer. We assessed the frequency and prognostic significance of Ep-CAM in tissue specimens from 205 patients with invasive breast cancer, by immunohistochemical staining with a monoclonal antibody specific for the Ep-CAM antigen. Ep-CAM overexpression was found in 35.6% of samples and was associated with poor disease-free and overall survival.

Antigens, Neoplasm↗
PubMed2000

A human common nuclear matrix protein homologous to eukaryotic translation initiation factor 4A.

Amino acid sequencing and mass spectrometry revealed identity of a human nuclear matrix protein, termed hNMP 265, with a predicted protein of gene KIAA0111. Two-dimensional electrophoresis and Northern hybridization showed the protein to ubiquitously occur in various human cell types. Exhibiting DEAD-box motifs characteristic for RNA helicases, hNMP 265 is highly similar to the human initiation factors eIF4A-I and -II. On the other hand, hNMP 265 greatly differs from the initiation factors by a N-terminal sequence rich in charged amino acids. Sequence searches and alignments indicate proteins related to hNMP 265 in other eukaryotes. Chimeras between hNMP 265 and green fluorescence protein or hapten appeared as speckles in extranucleolar regions in the nucleus, but not in the cytoplasm. Experiments with tagged deletion mutants indicated that the N-terminal amino acid sequence is necessary for nuclear localization. A putative role of hNMP 265 in pre-mRNA processing is discussed.

Amino Acid Sequence↗
PubMed2000

Improved technique for infrahepatic vena cava reconstruction in guinea pig-to-rat liver transplantation.

Guinea pig-to-rat orthotopic liver transplantation is associated with serious technical problems contributing to impaired graft perfusion and primary graft failure. In order to shorten the procurement procedure and thereby minimize liver damage before flushing, a simplified technique for infrahepatic caval reconstruction was developed. Dissection of the infrahepatic vena cava (IHVC) from adrenal glands and renal and lumbar veins represents the most difficult and time-consuming part of the donor operation, which is often not well tolerated by the animal; we avoided this step by using an isogeneic vena cava interposition graft (VCIG) following in situ perfusion. This graft is connected with the IHVC transsected just below the liver with a cuff technique. Donor operations lasted 15 to 20 minutes with the new technique (n = 7) compared to 52 to 76 minutes with conventional technique (n = 7). Reduced operating time was associated with markedly improved graft perfusion and significantly better graft survival. This modification of the donor procedure for the guinea pig-to-rat liver xenograft using a VCIG significantly reduces operating time and improves reperfusion and recipient survival.

Anastomosis, Surgical↗
PubMed2000

Regulation of transforming growth factor-beta secretion by human peritoneal mesothelial and ovarian carcinoma cells.

This study was conducted to compare the secretion of TGF-beta isoforms by human ovarian carcinoma (OVCA) cell lines (n=12) and human peritoneal mesothelial cells (HPMC;n=6) and to examine the regulation of their production by inflammatory cytokines. TGF-beta isoforms were furthermore analysed in OVCA-associated ascitic fluids. HPMC constitutively produced considerable amounts of TGF-beta1 (median 42 pg/10(5)cells; range 7-98) but only minimal amounts of TGF-beta2 (median 0.8 pg/10(5)cells; range 0-1.5). Treatment of HPMC with IL-1beta (10 ng/ml) resulted in a significant elevation of the secretion of both TGF-beta1 (median 187 pg/10(5)cells; range 71-264;P<0.001) and TGF-beta2 (median 1.8 pg/10(5)cells; range 0-13;P<0.01). In OVCA TGF-beta1 and TGF-beta2 were detected in 7/12 and 11/12 of the cell lines, respectively. The levels detected varied widely for TGF-beta1 (median 25 pg/10(5)cells; range 0-410) as well as for TGF-beta2 (median 14 pg/10(5)cells; range 0-419) and there was no correlation between the two isoforms. In contrast to HPMC, TGF-beta secretion by OVCA was not affected by any of the inflammatory cytokines tested. TGF-beta3 could not be detected in supernatants, neither in OVCA nor in HPMC. In ascitic fluids the median level of TGF-beta1 (median 5443 pg/ml; range 737-14687) was 10-fold higher than the level of TGF-beta2 (median 545 pg/ml; range 172-3537). The present data provide a model for the analysis of the molecular mechanisms of aberrant TGF-beta production by OVCA and support the hypothesis that HPMC are an important source of ascitic TGF-beta.

Ascites↗
PubMed2000

Incidence of intraabdominal infection in a consecutive series of 40 enteric-drained pancreas transplants with FK506 and MMF immunosuppression.

Although the introduction of FK506 and MMF has markedly improved patient and graft outcome after pancreas transplantation, this procedure is still associated with a high surgical complication rate. The aim of the following study was to retrospectively analyze a series of 40 consecutive pancreas transplants with enteric drainage with regard to intraabdominal infection (IAI). Between March 1997 and December 1998 a total of 40 whole pancreas transplants were performed. Prophylactic immunosuppression consisted of an intraoperative single shot ATG (Thymoglobulin), FK506, MMF, and prednisone. The mean observation period was 14.6 (5-26) months. Overall incidence of IAI was 27.5% (n = 11) leading to pancreatectomy in 5 patients (12.5%). In the remaining 6 patients the graft could be rescued by necrosectomy and radical drainage of the abscess (5 patients) or percutaneous drainage (1 patient). Pancreatectomy or local infection did not alter kidney graft function in the 11 patients with simultaneous pancreas kidney transplantation. In 10 patients no evidence for leakage at the site of enteric anastomosis was present, one duodenal leak occurred due to ischemia. IAI in the early postoperative period was the predominat risk factor for graft loss. An early and invasive diagnostic approach is recommended to maximize the chance of graft rescue.

Adult↗
PubMed2000

Clinically and mammographically occult breast lesions: detection and classification with high-resolution sonography.

With recent significant advances in ultrasound technology, the potential of high-resolution sonography to improve the sensitivity of cancer diagnosis in women with dense breasts has become a matter of interest for breast imagers. To determine how often physician-performed high-resolution sonography can detect nonpalpable breast cancers that are not revealed by mammography, 8,970 women with breast density grades 2 through 4 underwent high-resolution sonography as an adjunct to mammography. All sonographically detected, clinically and mammographically occult breast lesions that were not simple cysts were prospectively classified into benign, indeterminate, or malignant categories. Diagnoses were confirmed by ultrasound-guided fine-needle aspiration, core-needle biopsy, or surgical biopsy. In 8,103 women with normal findings at mammography and physical examination, 32 cancers and 330 benign lesions were detected in 273 patients with sonography only. Eight additional cancers were found in 867 patients with a malignant (n = 5) or a benign (n = 3) palpable or mammographically detected index lesion. The overall prevalence of cancers detected with screening sonography was 0.41%, and the proportion of sonographically detected cancers to the total number of nonpalpable cancers was 22%. The mean size of invasive cancers detected only by sonography was 9.1 mm, and was not statistically different from the mean size of invasive cancers detected by mammography. The sensitivity of prospective sonographic classification for malignancy was 100%, and the specificity was 31%. In conclusion, the use of high-resolution sonography as an adjunct to mammography in women with dense breasts may lead to detection of a significant number of otherwise occult cancers that are no different in size from nonpalpable mammographically detected cancers. Prospective classification of these lesions based on sonographic characteristics resulted in an acceptable benign-to-malignant biopsy rate of 6.3:1.

Adult↗
PubMed2000

Dendritic cells in precancerous lesions of the larynx.

OBJECTIVES: Hyperplastic lesions of the laryngeal mucosa can eventually develop into squamous cell carcinoma The relationship between dendritic cell infiltration of head and neck cancers and prognosis is well known. Surprisingly, data regarding dendritic cell infiltration in precancerous lesions are not available today. It was the purpose of our study to extend these observations and to investigate in more detail the density and distribution of dendritic cells in pre-cancerous lesions. STUDY DESIGN: Retrospective survey by immunohistochemistry. METHODS: For this study we investigated paraffin-embedded tissue sections of 41 specimens. Histological diagnosis disclosed precancerous lesions of the larynx in 34 cases and in 7 cases, squamous cell carcinoma Immunohistochemical study was performed using antibodies against the cell surface markers S-100, HLA-DR, CD20, CD45 RO, CD45 RA, and Lag. Typical dendritic cell distributions of the immunostained specimens were photographed and measured on a quantitative basis. The medical histories of the patients were then analyzed retrospectively. RESULTS: HLA-DR+ cells could be detected in 14 of 16 cases in mild dysplastic lesions. The infiltration of the dysplastic lesions was sparse compared to cases with higher-graded dysplastic lesions. The distribution patterns of the dendritic cells in specimens with severe dysplastic lesions, but squamous cell carcinoma were extremely similar and markedly different from those in grades I and II specimens. Memory T lymphocytes (CD45 RO+) were detected more often in the group with severe dysplastic lesions (8 of 9 cases) than in the group with squamous cell carcinoma (3 of 8 cases). The inverse became evident for CD20 and CD45 RA immunolabeling. CONCLUSIONS: Few dendritic cells were found in the precancerous lesions. This may suggest that these early lesions (grades I and H) are not efficiently monitored by the immune system. Therefore they may develop into carcinomas unimpaired by cytotoxic T cells. As the degree of malignancy rises (grade III), more dendritic cells infiltrate the tumor.

Aged↗
PubMed2000

Fluid shear stress induces heat shock protein 60 expression in endothelial cells in vitro and in vivo.

Recent investigations indicate that the initial event in the pathogenesis of atherosclerosis involves an (auto)immunologic injury to the vessel wall. Heat shock proteins (hsps), which are expressed on the endothelial cell surface, constitute possible autoantigens. After being exposed to shear stress of 30 dyne/cm(2) in vitro by means of a rotational viscometer, human umbilical vein endothelial cells were immunohistochemically stained for hsp 60 by the monoclonal antibody ML-30; static control cells were negative. Maximal hsp 60 induction was observed after 12 hours of hemodynamic stress. In Northern blots, the level of hsp 60 mRNA was markedly increased after only 1 hour of shear stress in human umbilical vein endothelial cells compared with static control cells. In vivo investigations in Lewis rats confirmed these in vitro findings: the intima and media of frozen sections of the right common carotid artery exposed to increased wall shear stress (after ligation of the left common carotid artery) were stained for hsp 60. The vessel wall of the left low-shear-stress-exposed side was negative. These findings demonstrate that shear stress results in hsp 60 induction in endothelial cells in vivo and in vitro, providing the prerequisite for humoral and cellular reactions to endothelial hsp in the earliest stages of atherosclerosis.

Animals↗
PubMed2000

Quantification and characterization of pregnancy-associated complexes of angiotensinogen and the proform of eosinophil major basic protein in serum and amniotic fluid.

BACKGROUND: The proform of eosinophil major basic protein (ProMBP) exists in serum from pregnant women complexed with a variable fraction of angiotensinogen (Ang). A subfraction further binds complement C3dg in a 2:2:2 complex. The function, physiology, and clinical importance of ProMBP complexes are unknown, and the specific quantification of these complexes has not been possible. METHODS: We developed an ELISA for the ProMBP/Ang complexes, using a monoclonal antibody against ProMBP for capture and a chicken anti-human Ang antiserum for detection. Calibrators were standardized with WHO IRP 78/610 for pregnancy proteins in the assay range 0.95-15.6 mIU/L. RESULTS: The concentrations of ProMBP/Ang complexes in serum of nonpregnant blood donors (n = 79) were log-normally distributed with a central 95th interval of 985-3655 mIU/L. In pregnancy, mean serum concentrations were increased from week 7, and the concentrations reached term concentrations in week 18. ProMBP/Ang complexes eluted in gel filtration as a broad peak with a molecular mass of approximately 230 kDa. The concentration of ProMBP/Ang/C3dg increased during blood coagulation, suggesting that the ProMBP/Ang/C3dg complex may be a marker of complement activation. CONCLUSIONS: ProMBP/Ang complexes are present in serum from nonpregnant persons as well as pregnant women, and the direct assays described here will make it possible to study the biochemistry and the clinical significance of different ProMBP complexes in pathological conditions and pregnancy.

Amniotic Fluid↗
PubMed1999

Incidental findings on sonography of the breast: clinical significance and diagnostic workup.

OBJECTIVE: The purpose of this study was to determine how often physician-performed high-resolution sonography can detect nonpalpable breast lesions not revealed by mammography. A sonographic classification scheme was tested for its accuracy in predicting malignancy of incidentally detected breast lesions. SUBJECTS AND METHODS: Six thousand one hundred thirteen asymptomatic women with breast density grades 2-4 and 687 patients with palpable or mammographically detected breast masses underwent sonography as an adjunct to mammography. All sonographically detected, clinically and mammographically occult breast lesions that were not simple cysts were prospectively classified into benign, indeterminate, or malignant categories. Diagnoses were confirmed by sonographically guided fine-needle aspiration or core needle biopsy. RESULTS: In 6113 asymptomatic women, 23 malignancies in 21 patients were detected with sonography only (prevalence, 0.31%). Five additional malignant lesions were found in patients with a malignant (n = 3) or a benign (n = 2) palpable or mammographically detected index lesion. The mean size of invasive malignancies detected only by sonography was 9.1 mm, which was not significantly different from the mean size of invasive cancers detected by mammography (p = .07). The sensitivity of the prospective sonographic classification for malignancy was 100%, and the specificity was 33.5%. CONCLUSION: The use of high-resolution sonography as an adjunct to mammography in women with dense breasts may lead to detection of a significant number of otherwise occult malignancies that are no different in size from nonpalpable mammographically detected lesions. Prospective classification of these lesions based on sonographic characteristics results in a significant reduction in number of unnecessary biopsies performed.

Aged↗
PubMed1998

Total gluteal pouching with pseudoanus caused by burn injury: report of a case.

PURPOSE: We report the case of a 69-year-old man who had suffered a third-degree burn injury of the buttocks close to the perianal region at the age of 2 years. Although initial attempts for conservative treatments failed, wound healing was achieved after numerous skin grafts. However, after prolonged healing, the patient developed scar contracture, resulting in total effacement of the gluteal folds and natal crease, and formation of a gluteal pseudoampulla and a pseudoanus. As a result of misinterpretation of the local anatomy, for the next 50 years the patient had to defecate into the gluteal pouch and empty this pseudoampulla by manually compressing the buttocks and irrigating with chamomile tea. METHOD: After a thorough examination revealed the presence of a normal, uninjured anus hidden by the scarred pouch, we excised this burn scar to expose the unburned perianal tissue and covered the resulting defect with a meshed, split-thickness skin graft. RESULT: Anorectal function was preserved, the anatomic contour was restored, and primary wound healing was achieved after one single-stage operation. CONCLUSION: To prevent such deformities, we recommend early excision and skin grafts as initial treatment, as opposed to conservative treatment, and thorough follow-up examinations to avoid misinterpretation of such a complex, altered local anatomy.

Aged↗
PubMed1997

[Value of MR tomography in inconclusive mammography findings].

PURPOSE: To evaluate the usefulness of magnetic resonance (MR) imaging in the assessment of inconclusive findings at mammography, such as indeterminate focal or diffuse breast abnormalities, post-treatment breasts with extensive scarring, dense breasts, and findings suggesting multifocal or multicentric breast cancer. MATERIAL AND METHODS: 254 patients underwent mammography, sonography, and MRI of the breast. Dynamic MR imaging was done using a thin-section three-dimensional gradient-echo sequence (FLASH, TR = 11.8 ms; TE = 5 ms; flip angle = 25 degrees) which was applied in a dynamic fashion before and every 90 seconds after injection of gadopentetate dimeglumine. Diagnoses were confirmed at biopsy (n = 165) or by follow-up (n = 89). RESULTS: Among various breast anomalies, the highest proportion of breast cancers was associated with dense breast tissue (27.8%), architectural distortion (26.9%), and irregular scars (15.8%). Sensitivity of dynamic MR imaging was 93.7%, and specificity was 83.3%. As compared to mammography and sonography, MR detected 6 occult carcinomas, and showed additional malignant lesions in 19/63 women (30.2%) with biopsy-proven breast cancer. CONCLUSION: MR imaging of the breast may provide valuable additional information in indeterminate breast anomalies. However, because of its inherent limitations, it should not replace core needle biopsy in all lesions which are amenable to biopsy. Because of its high sensitivity in the detection of invasive carcinomas in any type of breast tissue, MR imaging is considered the modality of choice in the evaluation of dense breasts in high-risk patients or in patients with clinical suspicion of occult breast cancer, and for preoperative tumor staging.

Breast↗
PubMed1997

Ovarian Sertoli-Leydig cell tumor: a SRY gene-independent pathway of pseudomale gonadal differentiation.

Sertoli-Leydig cell tumors (SLCT) are rare sex-cord stromal tumors of the ovary composed of undifferentiated gonadal stromal cells, Leydig cells (LC), and Sertoli cells (SC), with the latter forming structures resembling fetal testicular tubules. The histogenetic basis of morphological male differentiation patterns in females is controversial. Here, we report a SLCT with intermediate differentiation in a 23-year-old woman investigated by light microscopy, immunohistochemistry for intermediate filaments, and sex steroid hormone receptors (SSHR), as well as by polymerase chain reaction (PCR) for the presence of the sex-determining region Y gene (SRY). Our investigation shows that the SCs of SLCT express progesterone and androgen receptors as well as cytokeratins and vimentin. By PCR, SLCT-derived genomic DNA lacked the SRY gene, indicating that the SLCT results from a SRY gene-independent pathway of pseudomale gonadal differentiation. The expression of progesterone receptors (PRs) in the SCs of the SLCT is in contrast to their absence in testicular SCs, but in line with their presence in ovarian granulosa and surface epithelial cells. Thus, our results provide strong evidence for a close histogenetic relationship between the SLCT and the female gonocyte-supporting cell, the granulosa cell (GC).

Adult↗
PubMed1996

Human peritoneal mesothelial cells are more potent than ovarian cancer cells in producing tumor marker CA-125.

The aim of the present study was to investigate the extent to which human peritoneal mesothelial cells (HPMCs) are able to participate in the release of tumor marker CA-125 in ovarian cancer and other conditions associated with an involvement of the peritoneum. For this purpose CA-125 shedding was measured in the supernatant culture medium of HPMCs obtained from various donors and seven well-established ovarian cancer cell lines (OVCAR-3, 2780, 2774, SKOV-6, SKOV-8, HOC-7, HTB-77). Furthermore, the influence of inflammatory cytokines [interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma)] on CA-125 release in normal and malignant cells was also studied. Constitutive CA-125 shedding was found to be about five times higher in HPMCs as compared with the investigated ovarian cancer cell lines. IL-1 beta and TNF-alpha treatment of HPMCs resulted in a significant reduction in CA-125 release; however, no consistent pattern in CA-125 secretion was found during incubation with either IL-1 beta or TNF-alpha in the various malignant cell lines. IFN-gamma, on the other hand, induced a highly significant increase in CA-125 secretion in ovarian cancer cells, but did not influence the shedding of CA-125 in HPMCs.

CA-125 Antigen↗