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S Gebhard

Publications and source records attributed to S Gebhard.

25 records · Page 2Linked to original sources
PubMed1994

Primary malignant mixed Müllerian tumor (metaplastic carcinoma) of the female peritoneum. A clinical, pathologic, and immunohistochemical study of three cases and a review of the literature.

BACKGROUND: Malignant mixed mesodermal tumors (malignant mixed Müllerian tumors [MMMT]) occur rarely in extragenital sites. METHODS: The authors analyzed the clinical, pathologic, and immunohistochemical features of three cases of primary MMMT of the female peritoneum. RESULTS: The neoplasms occurred in 60-, 64- and 84-year-old women and arose from pelvic peritoneum. Two patients died with disseminated disease 8 and 24 months postoperatively. The third died of cardiac failure 12 months postoperatively with questionable metastatic disease. Microscopically, two tumors were of the heterologous type, containing foci of rhabdomyosarcomatous (case 1) and chondrosarcomatous (case 3) differentiation. Immunohistochemically, coexpression of keratin and vimentin was observed focally in both carcinomatous and sarcomatous components in all three neoplasms, whereas coexpression of low molecular weight cytokeratin, vimentin and actin was observed focally in case 2. Rhabdomyosarcomatous areas were positive with desmin and actin, and chondrosarcomatous areas for S-100 protein. Both epithelial and mesenchymal components were positive for alpha-1 antichymotrypsin in all cases. CONCLUSIONS: On the basis of the present cases and a review of 15 reports from the literature, primary MMMT of the female peritoneum proved to be a rare but highly malignant neoplasm occurring in elderly postmenopausal women. Of 15 patients with available follow-up, 12 died with disease, mostly within 1 year, regardless of the initial tumor stage, histology (homologous versus heterologous MMMT) or treatments attempted. The tumor developed within pelvic peritoneum in half the cases. Histogenetically, peritoneal MMMT are thought to represent "metaplastic" carcinomas originating from the secondary Müllerian system.

Actins↗
PubMed1994

Glycolaldehyde causes DNA-protein crosslinks: a new aspect of ethylene oxide genotoxicity.

After in vitro incubation of human peripheral mononuclear blood cells with glycolaldehyde (a putative metabolite of ethylene oxide) for 2 h at 37 degrees C, a dose-dependent increase in DNA crosslinks was observed in a dose range between 1 and 10 mM using the alkaline filter elution technique. The elution rate of mononuclear blood cells after treatment with ionizing radiation (600 cGy) was reduced more than 5-fold if cells were incubated with 10 mM glycolaldehyde for 2 h. After treatment with proteinase K DNA crosslinks were no longer detected in cells incubated with glycolaldehyde. Therefore the crosslinks produced by glycolaldehyde could clearly be identified as DNA-protein crosslinks. Additionally glycolaldehyde induced DNA single-strand breaks in a dose range between 1 and 10 mM. The elution rate of mononuclear blood cells was increased about 18-fold if cells were incubated with 5 mM glycolaldehyde for 2 h using an elution procedure with proteinase K. In vitro incubation of mononuclear cells with ethylene oxide for 2 h at 37 degrees resulted in a dose-dependent increase in DNA single-strand breaks between 0.5 and 10 mM ethylene oxide. Moreover, a time-dependent increase in DNA single-strand breaks after incubation with 1.5 mM ethylene oxide was observed with an increased number of single-strand breaks already detectable after 15 min and a maximum level which was detected after 2 h of incubation. However, no DNA-DNA or DNA-protein crosslinks could be detected although a wide concentration range and many different incubation times were tested. Therefore DNA crosslinks, for which evidence was found in mononuclear blood cells of humans occupationally exposed to ethylene oxide, are possibly generated by glycolaldehyde, a putative intermediate in the metabolism of ethylene oxide to glycolic acid.

Acetaldehyde↗
PubMed1993

Oestrogen receptor, progesterone receptor, pS2, ERD5, HSP27 and cathepsin D in invasive ductal breast carcinomas.

Hormonal receptors and markers for prognostic evaluation were detected immunohistochemically in 196 infiltrating ductal breast carcinomas. Immunohistochemical detection of progesterone and oestrogen receptor is a method giving results generally concordant with those of the binding assay. However, immunohistochemical detection seems better. It allows the detection of hormonal receptors on small carcinomas, it is not modified by the endogenous hormones, and it has a slightly better correlation with prognosis and with the response to hormone therapy. Immunohistochemical detection of progesterone receptor has a prognostic value, sorting a negative subgroup with a poor prognosis from the oestrogen receptor positive tumours. These results can be obtained without quantitative immunohistological methods. ERD5, pS2, HSP27 and cathepsin D are associated with oestrogen receptor positivity. pS2 and HSP27 are interesting markers. They characterize a subgroup of oestrogen receptor negative tumours with a good prognosis. Moreover, pS2 is a marker of response to hormone therapy. ERD5 and cathepsin D do not appear to be of value as markers of prognosis.

Adult↗
PubMed1991

[Assessment of respiratory physiology signals in very low-weight newborn infant with respiratory deficiency].

1. Lung function tests in newborn babies breathing spontaneously were performed commonly using a pneumotachometer to measure the tidal volume and an esophageal catheter to measure the transpulmonary pressure changes. 2. The quality of the measured signals depends on the breath-to-breath variability of the signals as well as on the frequency of different artifacts and disturbances due to physiological interferences. 3. The evaluation of the signals in very low birth weight infants with respiratory distress is often difficult due to the irregular pattern of respiration, the reduced signal-noise-ratio and the high number of artifacts. 4. The subjective assessment of the quality of 115 records of respiratory signals has shown that 54% of all records can be evaluated easily, in 40.8% the evaluation was difficult and in 5.2% an evaluation was not possible. 5. The qualitative analysis of respiratory signals shows that in this age group the computer-aided signal evaluation requires a new view in the detection and elimination of artifacts as well as in the calculation of characteristic results from a sufficient number of evaluated breathing cycles.

Humans↗
PubMedDate not supplied

Mutation analysis of the cationic trypsinogen gene in patients with pancreatic cancer.

Recently, an Arg to His mutation at residue 117 of the cationic trypsinogen gene (Arg117His) has been shown to be associated with hereditary pancreatitis (hp). A serious complication of hp is development of pancreatic cancer. Patients suffering from hp have been reported to have a 53-fold increased risk to die from pancreatic cancer. However, the quantitative contribution of mutations in the cationic trypsinogen gene to all pancreatic cancer cases is unknown. A relevant contribution of the Arg117His-mutation to pathogenesis of pancreatic cancer might be possible, since also asymptomatic individuals have been reported to carry this mutation and individuals with only mild symptoms may be undiagnosed as hp. In the present study we analyzed genomic DNA obtained from pancreatic cancer tissue from 34 patients and corresponding normal tissue from 28 of these individuals. The third exon of the cationic trypsinogen gene was amplified by nested PCR and digested with AflIII, since the Arg117His mutation creates an AflIII-restriction site. None of the examined samples carried the Arg117His mutation, whereas the amplification product obtained from a patient with known hp was clearly positive. Sequencing of the complete third exon of the cationic trypsinogen gene in 10 of the pancreatic cancer patients resulted exclusively in the wild-type sequence. In addition DNA obtained from venous blood of 116 further patients with pancreatic cancer did not carry the Arg117His mutation. Our results show that the Arg117His mutation does not contribute to pathogenesis of a substantial fraction of all pancreatic adenocarcinomas. In contrast to most oncogenes or tumor suppressor genes the cationic trypsinogen gene (3rd exon) does not contain mutational hot spots.

Adenocarcinoma↗
PubMedDate not supplied

Angiogenesis and fibroblast proliferation precede formation of recurrent tumors after radiation therapy in nude mice.

Recently, the combination of ionizing radiation with inhibitors of angiogenesis has been reported to improve tumor eradication compared to treatment with irradiation alone. However, the mechanisms of this effect have not been defined. For this purpose [corrected] we established a non-small cell lung cancer model in nude mice. Tumor vascularization was visualized in vivo by MRI using gadolinium-DTPA as contrast agent. Further, cryosections were produced as close as possible to the MRI slice positions. Since we were interested in examining the formation of a recurrent tumor, irradiation was performed with a single fraction of 4 Gy. This dose caused a partial remission followed by recurrent tumor growth 25 to 35 days after therapy. The process of partial remission as well as formation of the recurrent tumor was examined in 28 nude mice analysing the following parameters: (i) contrast agent enhancement using high-resolution MRI, (ii) proliferation of tumor cells and fibroblasts using Ki-67 immunohistochemistry and (iii) formation of microvessels using CD31 immunohistochemistry. The latter analyses led to differentiation of three stages. Stage 1 (day 1 to day 15 after irradiation) was characterized by increasing areas of dead cell mass in hematoxylin-eosin-stained slides that corresponded to a decrease in tumor cell proliferation as well as contrast agent enhancement in MRI. The percentage of Ki-67-positive tumor cells decreased from initially 45.1% +/- 6.0% (mean +/- standard deviation) to 1.4% +/- 1.2% (mean +/- standard deviation) on day 15. Stage 2 (day 6 to day 20 after irradiation; overlapping with stage 1) was characterized by proliferation of fibroblasts leading to formation of fibrotic septae with abundant microvessels. Already during late stage 2, MRI identified new contrast agent enhancing areas. Stage 3 (day 20 to day 40 after irradiation) was characterized by new tumor cell proliferation. Interestingly, tumor cells almost exclusively proliferated in the direct neighbourhood of the fibrotic septae that had been formed in stage 2. Obviously, proliferation of fibroblasts and blood vessels was a condition prior to formation of recurrent tumor tissue. Thus, our results are in contrast with the view that tumors or recurrent tumors begin as avascular masses that later induce neovascularization. With respect to clinical practice, our results suggest that: (i) adjuvant anti-angiogenic therapy should not be limited to the day of irradiation but should cover a critical period until day 5 to day 20 after radiotherapy, (ii) adjuvant therapy should also include inhibition of fibroblast proliferation and (iii) MRI can identify a recurrent tumor 10 to 15 days before occurrence of new tumor growth.

Animals↗