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J Mueller

Publications and source records attributed to J Mueller.

At least 19 recordsLinked to original sources

Behavior and occurrence of estrogens in municipal sewage treatment plants--I. Investigations in Germany, Canada and Brazil.

The developed method enables the quantification of estrogens in sewage samples down to 1 ng/l and in river water down to 0.5 ng/l. Mean recoveries of the analytes in ground water after SPE extraction, clean-up and derivatization generally exceeded 75%. The determined R.S.D. varied from 0 to 14% at a spiking level of 0.05 microgram/l. Even in the raw influent and the final effluent from municipal STPs the mean recoveries of estrogens were mostly above 70%. Using this method the behavior and occurrence of natural estrogens and synthetic contraceptives in municipal sewage treatment plants (STP) were investigated in German and Canadian facilities. In the sewage of a German municipal STP close to Frankfurt/Main 17 beta-estradiol and estrone were determined, with mean concentrations of 0.015 microgram/l and 0.027 microgram/l, respectively. In two investigated municipal STPs, 17 beta-estradiol and 16 alpha-hydroxyestrone were eliminated with a higher efficiency than 17 alpha-ethinylestradiol and estrone. In Canadian and German STP discharges estrone, 17 beta-estradiol, 17 alpha-ethinylestradiol and 16 alpha-hydroxyestrone were frequently detected within the lower ng/l-range. A maximum concentration was found for estrone with 70 ng/l. In 15 investigated German rivers and streams only estrone was present with a maximum concentration of 1.6 ng/l.

Animals

Behaviour and occurrence of estrogens in municipal sewage treatment plants--II. Aerobic batch experiments with activated sludge.

Aerobic batch experiments containing a diluted slurry of activated sludge from a real sewage treatment plant (STP) near Frankfurt/Main were undertaken, in order to investigate the persistence of natural estrogens and contraceptives under aerobic conditions. The batch experiments showed that while in contact with activated sludge the natural estrogen 17 beta-estradiol was oxidized to estrone, which was further eliminated in the batch experiments in an approximate linear time dependence. Further degradation products of estrone were not observed. 16 alpha-hydroxyestrone was rapidly eliminated, again without detection of further degradation products. The contraceptive 17 alpha-ethinylestradiol was principally persistent under the selected aerobic conditions, whereas mestranol was rapidly eliminated and small portions of 17 alpha-ethinylestradiol were formed by demethylation. Additionally, two glucuronides of 17 beta-estradiol (17 beta-estradiol-17-glucuronide and 17 beta-estradiol-3-glucuronide) were cleaved in contact with the diluted activated sludge solution and thus 17 beta-estradiol was released. The glucuronidase activity of the activated sludge was further confirmed by the cleavage of 4-methylumbelliferyl-beta-D-glucuronide (MUF-beta-glucuronide) in a solution of a activated sludge slurry and Milli-Q-water (1:100, v/v). The turnover rate obtained was approximately steady state, with a turnover rate of 0.1 mumol/l for the released MUF. Hence, it is very likely that the glucuronic acid moiety of 17 beta-estradiol glucuronides and other estrogen glucuronides become cleaved in a real municipal STP, so that the concentrations of the free estrogens increase.

Aerobiosis

Loss of immunohistochemical E-cadherin expression in colon cancer is not due to structural gene alterations.

E-cadherin, a transmembrane cell adhesion molecule, has been observed to have an altered pattern of immunoreactivity in several types of carcinomas. In lobular breast cancer, loss of immunoreactivity has been shown to be due either to out-of-frame deletions or to nonsense mutations of the E-cadherin gene. We analysed 29 cases of completely resected colon carcinoma with immunohistochemistry using the HEC-D1 antibody. Normal protein expression similar to that in the adjacent nonmalignant mucosa was seen in 6 cases, whereas 23 tumours had reduced or absent E-cadherin expression. In the 8 cases with no expression of E-cadherin revealed by immunohistochemistry, the entire E-cadherin cDNA sequence was analysed. In these cases, sequence analysis failed to reveal any cDNA mutations despite the negative immunohistochemistry. Possible explanations for this discrepancy include regulatory defects in the E-cadherin promoter, abnormalities at the translation or protein processing levels and mutations in other parts of the gene that were not investigated by the cDNA analysis (e.g. intronic sequences), which could play a role in causing abnormal processing of the E-cadherin protein.

Adult

Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation.

E-Cadherin alterations have been reported frequently in sporadic diffuse type gastric and lobular breast carcinomas. Germline mutations of this gene have been identified recently in several gastric cancer families. We analyzed seven patients with a family history of the disease who had diffuse type gastric cancer diagnosed before the age of 45 for germline mutations in CDH1, the gene encoding the E-cadherin protein. We identified a frameshift mutation in exon 3 in one patient with a strong family history of gastric cancer. The same germline mutation was found in the patient's mother, who had metachronous development of lobular breast and diffuse type gastric carcinomas. Immunohistochemistry for E-cadherin protein expression revealed an abnormal staining pattern in both of these tumors, suggesting complete inactivation of the cell adhesion molecule. Thus, our finding suggests that besides diffuse type gastric cancer, lobular breast carcinomas may be associated with germline CDH1 mutations.

Adult

The differentiation of true adenomas from colitis-associated dysplasia in ulcerative colitis: a comparative immunohistochemical study.

Adenomas in areas involved by ulcerative colitis (UCA) are difficult to identify because of their morphological similarity to ulcerative colitis-associated dysplasia (UCD) and have an uncertain biology. Recently, a set of morphopathologic criteria were published for the diagnosis of UCA versus UCD. As a first step to analyze these criteria, we studied p53 and bcl-2 expression in groups of UCA and UCD along with a sporadic adenoma control group. Ninety lesions from UC areas (62 patients) were examined, including 24 UCA without high-grade dysplasia (HGD) and 66 UCD consisting of 43 polypoid and 23 flat dysplastic lesions (29 with HGD). Immunohistochemical p53 and bcl-2 expression were evaluated semiquantitatively. P53-positive cases were significantly less frequent in the UCA (4%) versus the UCD group (30%, P = .01) and the polypoid UCD subgroup (35%, P = .005). Moderate or strong bcl-2 expression was significantly more frequent in the UCA than in the UCD group (96% v 70%, P = .01) and in the UCA versus both polypoid and flat UCD subgroups. Comparison of UCA with low-grade dysplastic polypoid UCD cases alone showed a difference just below significance for p53 (P = .07). p53 and bcl-2 expression rates were very similar in the UCA group and the sporadic adenoma (n = 25) control group. These results show that UCA has phenotypic features more similar to sporadic adenomas than UCD and supports the concept that adenomas in UC have a biology different from UC-associated dysplasia.

Adenoma

Auxiliary total artificial heart: A compact electromechanical artificial heart working simultaneously with the natural heart.

Leading international institutions are designing and developing various types of ventricular assist devices (VAD) and total artificial hearts (TAH). Some of the commercially available pulsatile VADs are not readily implantable into the thoracic cavity of smaller size patients because of size limitation. The majority of the TAH dimensions requires the removal of the patients' native heart. A miniaturized artificial heart, the auxiliary total artificial heart (ATAH), is being developed in these authors' laboratories. This device is an electromechanically driven ATAH using a brushless direct current (DC) motor fixed in a center metallic piece. This pusher plate-type ATAH control is based on Frank-Starling's law. The beating frequency is regulated through the change of the left preload, assisting the native heart in obtaining adequate blood flow. With the miniaturization of this pump, the average sized patient can have the surgical implantation procedure in the right thoracic cavity without removing the native heart. The left and right stroke volumes are 35 and 32 ml, respectively. In vitro tests were conducted, and the performance curves demonstrate that the ATAH produces 5 L/min of cardiac output at 180 bpm (10 mmHg of left inlet mean pressure and 100 mm Hg of left outlet mean pressure). Taking into account that this ATAH is working along with the native heart, this output is more than satisfactory for such a device.

Blood Pressure

Long-term in vivo left ventricular assist device study for 284 days with Gyro PI pump.

A totally implantable centrifugal artificial heart has been developed. The plastic prototype, the Gyro PI 601, passed 2 day hemodynamic tests as a functional total artificial heart (TAH), 2 week screening tests for anti-thrombogenecity, and a 1 month system feasibility study. Based upon these results, a metallic prototype, the Gyro PI 700 series, was subjected to long-term in vivo left ventricular assist device (LVAD) studies of over 1 month. The Gyro PI 700 series has the same inner dimension and same characteristics of the Gyro PI 601 such as an eccentric inlet port, a double pivot bearing system, and a magnet coupling system. The PI metallic pump is also driven with the Vienna DC brushless motor actuator like the PI 601. The pump-actuator package was implanted in 3 calves in the preperitoneal space, bypassing from the left ventricular (LV) apex to the descending aorta. Case 1 achieved a 284 day survival. Case 2 was euthanized early at 72 postoperative days as a result of the functional obstruction of the inlet port due to the excessive growth of the calf. There was no blood clot inside the pumps of either case. Case 3 is on-going (22 days on July 24, 1998). During these periods, all cases showed no physiological abnormalities. In conclusion, the PI 700 series pump has excellent results as a long-term implantable LVAD.

Animals

Rapid detection of mutated E-cadherin in peritoneal lavage specimens from patients with diffuse-type gastric carcinoma.

Tumor cells in abdominal lavage specimens from patients with gastric carcinoma strongly predict subsequent peritoneal metastasis and poor prognosis. Reverse transcription (RT)-polymerase chain reaction (PCR) detection of wild-type E-cadherin has been claimed to be superior to conventional cytology for the detection of patients who subsequently develop peritoneal metastases. The present study tested this hypothesis and determined whether or not the detection of mutated, tumor-specific E-cadherin messenger RNA in abdominal lavage specimens serve as a useful diagnostic tool. Preoperative lavage specimens from 52 patients with diffuse-type gastric carcinoma and from 5 patients with benign disease were analyzed by conventional cytology and by RT-PCR for amplification of E-cadherin. Tumor cells were detected by cytology in 8 (15.3%) of the 52 patients with gastric cancer. The E-cadherin was detected in all 57 samples by RT-PCR. Two of these had abnormal E-cadherin amplification products confirmed to be mutations by direct sequencing, which were identical in the primary tumors. These findings suggest that the detection of wild-type E-cadherin is not sufficiently tumor specific. Also, for diffuse gastric carcinomas with confirmed E-cadherin mutations, detection of mutant E-cadherin by RT-PCR is a potentially valuable method for tumor cell detection in lavage specimens.

Ascitic Fluid

So-called carcinosarcoma of the esophagus: A clinicopathologic, immunohistochemical and DNA flow-cytometric analysis of 6 cases.

Six cases of carcinosarcoma of the esophagus were studied clinicopathologically, immunohistochemically and with DNA flow cytometry. Transitional areas with morphology intermediate between carcinoma and sarcoma were found microscopically in all cases. Immunohistochemically, the carcinomatous areas contained keratin-positive cell components in all cases while vimentin-positive cells were found in sarcomatous areas in 5 cases. By DNA flow analysis of microdissection, the sarcomatous components of the tumors showed an aneuploid pattern with one exception, in contrast the carcinomatous components were diploid in all cases. In these few cases, PCNA, S-phase fraction and the mitotic rate were extremely high, apparently indicating a correlation with malignant behavior. Accordingly, examination by immunohistochemistry and DNA ploidy is useful for the analysis of biological properties in the so-called carcinosarcoma of the esophagus.

Aged

The molecular pathology of Barrett's esophagus.

The incidence of adenocarcinoma of the distal esophagus is rapidly increasing in the Western world. The histopathological sequence of (Barrett's) metaplasia, which develops as a consequence of chronic reflux, to dysplasia and then to carcinoma is well established for these tumors. In Barrett's esophagus a variety of molecular changes have been characterized and correlated with tumor initiation and progression. Among the early changes in premalignant stages of metaplasia are alterations of the transcripts of FHIT, a presumptive tumor suppressor gene which spans the common fragile site FRA3B. Mutations of p53 seem to accumulate mainly in the transition from low to high grade dysplasia. Inactivation of other tumor suppressor genes by mutation (APC, p16) or hypermethylation (p16) as well as amplification of oncogenes such as cerbB2 are relatively late events in the development of adenocarcinoma. Among the phenotypic changes in Barrett's esophagus are an expansion of the Ki67 proliferation compartment which correlates with the degree of dysplasia. Moreover, accumulation of rab11 molecules which are involved in membrane trafficking has been reported to be specific for the loss of polarity seen in low grade dysplasia. Reduced expression of the cadherin/catenin complex as well as increased expression of various proteases develop chiefly in invasive carcinomas. Despite the progress that has been made in the identification of molecular markers in Barrett's carcinoma, to date the histopathological diagnosis of high grade dysplasia in endoscopic biopsies remains the best predictor of invasive cancer. Immunohistochemistry applying a panel of antibodies including p53, Mib-1 or rab11 can be helpful to diagnose regenerative metaplastic epithelium or low and high grade dysplasia.

Barrett Esophagus

Micrometastasis and tumor cell microinvolvement of lymph nodes from esophageal squamous cell carcinoma: frequency, associated tumor characteristics, and impact on prognosis.

BACKGROUND: The purpose of this study was to investigate micrometastasis (MM) and tumor cell microinvolvement (TCM) in the regional lymph nodes of patients with esophageal squamous cell carcinoma (SCC). METHODS: MM was defined as individual tumor cells or tumor cell clusters <0.5 mm in greatest dimension with a surrounding stromal reaction. TCM was defined as individual tumor cells or tumor cell clusters without a surrounding stromal reaction. One thousand nine hundred and fifty-four lymph nodes were dissected from 69 complete (R0) resection specimens of TNM classified pT1-3, pN0 or pN1, and M0 esophageal SCC. These lymph nodes were examined immunohistochemically using the monoclonal antibody cocktail AE1/AE3 for cytokeratins. The primary tumors were immunostained with an anti-E-cadherin monoclonal antibody. RESULTS: MM +/- TCM was found in 13 cases (31.7%) and TCM alone in 2 cases (4.9%) of the 41 pN0 cases. The pN0 patients with MM (but not TCM) had the same shorter survival as the original pN1 cases (P < 0.05). Of the 69 primary tumors, 49 (71.0%) had reduced or negative E-cadherin expression that showed a correlation with the occurrence of lymph node metastases (original pN1), MM, and TCM, but not prognosis. CONCLUSIONS: The results of the current study show that, in SCC of the esophagus, MM, but not TCM, in the regional lymph nodes is prognostically equivalent to metastasis and should be examined by immunohistochemistry to classify these cases correctly as pN1.

Adult

Diffusely infiltrative squamous cell carcinoma of the esophagus.

This study was designed to clarify the clinical and pathologic features of diffusely infiltrative squamous cell carcinoma of the esophagus. Diffusely infiltrative squamous cell carcinomas were classified grossly into two types, namely, scirrhous carcinoma and nonscirrhous carcinoma. There were seven patients with the former type and three with the latter type. Scirrhous-type carcinoma was associated with a prominently thickened esophageal wall with strictures, whereas nonscirrhous-type carcinoma demonstrated thickening of the esophageal wall without strictures. Microscopically, all patients had lymph node metastases and lymphatic invasion. Blood vessel invasion was found in seven patients and extranodal invasion was found in seven. The prognosis of patients with both types of carcinoma was extremely poor. Only two patients who underwent curative surgery as well as chemoradiotherapy survived for more than 1 year. Therefore, further morphological studies on the early stages of diffusely infiltrating esophageal carcinoma should be performed. New treatment strategies such as intensive preoperative chemoradiotherapy based on sensitivity tests in individual patients will be required for treating the advanced stages of this disease.

Aged

Loss of heterozygosity of the von Hippel Lindau gene locus in polypoid dysplasia but not flat dysplasia in ulcerative colitis or sporadic adenomas.

Carcinoma in ulcerative colitis (UC) develops from dysplastic precursor lesions, which include flat dysplasia (FD) and polypoid dysplasias (PD). PD may present as single or multiple polypoid structures or as plaque-like lesions that, independent of histological grade, are an indication for colectomy. PDs are histologically similar to adenomas and may not be readily distinguished by light microscopy. It is not known whether FD and PD are different entities, or whether they represent etiologically similar lesions with different morphological expression. We microdissected 25 cases of UC with PD and 19 samples of FD with surrounding chronic colitis (CC) in UC. Loss of heterozygosity (LOH) at the von Hippel Lindau (vHL) gene locus and the putative tumor suppressor genes APC, INK4A (9p16), and p53 was studied. LOH of the vHL gene, INK4A (9p16), and APC was also studied in 11 sporadic adenomas of the colon. LOH at the vHL locus was present in 50% of the samples of PD and in 12% of the samples of FD. LOH was seen in CC close to PD and FD in 26% and 12% of cases, respectively. No adenoma showed LOH of the vHL gene markers studied. LOH in p53 was seen in PD in 16% cases and in FD in 42% cases and in CC close to PD and FD in 0% and 14% cases, respectively. LOH patterns between PD and FD of the markers for APC and 9p16 were not different. LOH in APC was seen in two of five cases of adenoma. We conclude that PD and FD share genetic alterations in APC and 9p16 genes. More frequent involvement of the VHL gene in PD and surrounding CC and involvement of p53 in HGD and CC in FD may represent genetic differences between the development of PD and FD and may be the cause of the different morphology. The infrequency of LOH at the vHL locus in adenomas versus PD may serve as a discriminator between adenomas and PD in diagnostically problematic cases.

Adenoma

In vivo evaluation of the miniaturized Gyro centrifugal pump as an implantable ventricular assist device.

A miniaturized Gyro centrifugal pump has been developed to be incorporated into a totally implantable artificial heart. The Gyro PI (permanently implantable) model is a pivot bearing supported centrifugal pump with a priming volume of 20 ml. With the miniaturized actuator, the pump-actuator package has a height of 53 mm, a diameter of 65 mm, and a displacement volume of 145 ml. To evaluate the hemocompatibility and efficiency of the Gyro PI pump system, a plastic prototype (Gyro PI-601) was implanted into a bovine model as a left or right ventricular assist device (LVAD or RVAD), bypassing from the left ventricular apex to the descending aorta or from the right ventricular infundibulum to the main pulmonary artery. The calves were anticoagulated with heparin to maintain activated clotting times from 150 to 200 s. Four calves were supported for 23, 24, and 50 days in the LVAD studies, and 40 days in the RVAD study. The first calf died due to intrathoracic bleeding associated with sepsis. The second calf was euthanized for a low flow rate less than 2 L/min due to an obstructed inflow with growing pannus. The third and fourth calves were euthanized as scheduled. Renal and hepatic functions remained normal, and plasma free hemoglobin values were less than 8 mg/dL throughout the experiments. The fourth case showed flow rates of 4.83 +/- 0.57 L/min, input power of 6.16 +/- 0.49 W, and the inside temperature of the actuator of 43.5 +/- 0.52 degrees C. The pumps implanted in the fourth calf demonstrated no thrombus formation at the autopsy. These in vivo experiments revealed that the Gyro PI pump can provide adequate flow as an easily implantable, efficient, antithrombogenic, and nonhemolytic centrifugal LVAD or RVAD with miniaturized actuators.

Animals

Estimation of the native cardiac output from a rotary blood pump flow: in vitro study.

The rotary blood pump will be an implantable left ventricular assist device (LVAD) in the near future. However, the best control method and the interrelationship between the rotary blood pump and native heart functions are unclear. An estimation was made of the native heart cardiac output from the change of an LVAD's outflow waveform. The mock circulation loop was composed of an aortic compliance chamber, left arterial chamber, total artificial heart as a native heart, and a rotary blood pump that was placed as an LVAD with left ventricular drainage. The fast Fourier transform (FFT) technique was utilized to analyze the LVAD's outflow waveform and calculate the pulse power index (PPI) to examine a relation between the PPI and total artificial heart (TAH) output. The PPI increased with the increase of the TAH output; there was a positive correlation, and there was an inverse correlation between the PPI and the assist ratio. From this viewpoint, an estimation of the pulsatility change of the LVAD's outflow wave may indicate the native cardiac output.

Aorta

p53 genetic alterations, protein expression and autoantibodies in human colorectal carcinoma: A comparative study.

This study investigated a total number of 120 colorectal malignant tumor tissues by applying a new quantitative luminometric assay (LIA)-mat, immunohistochemistry (IHC) (n=100), PCR/SSCP (n=42), and sequencing (n=7). Sera were collected from 235 patients suffering from colorectal carcinoma in addition to 195 healthy individuals as a control group. Manual ELISA kit was developed to detect p53 autoantibodies in the sera of those patients. Our data demonstrated that the LIA-mat yields reliable estimates of p53 expression in soluble cell extracts as compared with results obtained by immunohistochemistry which showed positive immunostaining in 63% of the studied cases. Using a cut-off value of 1.8 ng/mg protein, 65 tumors out of 120 (54%) were classified to be positive by LIA-mat, manifesting protein overexpression, while 22 out of 42 (52%) tumor samples showed p53 gene alteration when applying single strand conformation polymorphism (SSCP) analysis on polymerase chain reaction products. In tumor samples without a p53 gene alteration, the median soluble p53 protein level was 4.3 ng/mg protein, whereas the median p53 protein level for tumor samples with p53 gene alteration was 7.5 times higher. Despite a significant correlation between the outcome of LIA and SSCP, a disagreement was found in 30% of cases. We found no significant correlation between p53 protein overexpression and clinicopathological findings except for distant metastasis (p=0.33), indicating p53 immunoreactivity to be an independent prognostic factor. Our data showed that 18% of patients suffering from colorectal cancer developed autoantibodies against p53 in their sera which might be an early indicator for tumor development and distant metastasis.

Autoantibodies

Microsatellite instability and loss of heterozygosity in gastric carcinoma in comparison to family history.

We compared 29 gastric carcinomas from patients with a variably strong family history for gastric cancer (group 1) with 36 gastric carcinomas from patients without a family history of this disease (group 2) for microsatellite instability (MSI) and loss of heterozygosity (LOH) with 12 microsatellite markers. Both study groups had similar proportions of histological types and tumor locations. Widespread MSI (alterations at > or = 6 loci) was seen in 5 of 29 (17%) of the tumors belonging to group 1 and in 4 of 36 (11%) group 2 tumors. MSI at a low level (alterations at 1 to 3 loci) was observed in 12 of 29 (41%) of tumors in group 1 and in 10 of 36 (28%) of tumors in group 2, differences that were not statistically significant. A significant difference with respect to low level MSI was observed between the two groups when considering the overall mutation rate of microsatellites. Seventeen of 281 (6%) analyzed microsatellite loci showed alterations in group 1 and 11 of 381 (2.9%) in group 2 (P = 0.046). Comparison of both types of MSI to the clinicopathological parameters in both groups revealed a significant association of low level MSI with advanced tumor stages (P = 0.046) in the group 2, whereas no such association was observed in group 1. In respect to LOH, a significant difference between the two groups was observed at chromosome 17p12, as 13 of 22 (59%) informative cases of group 1 showed LOH in comparison with 7 of 26 (27%) (P = 0.024) in group 2. No correlation of LOH at chromosome 17p12 to the pathological or clinical data was observed either in the two groups or in the study as a whole. Our data show that gastric carcinomas of patients with a positive family history of gastric cancer in group 1 are characterized by a higher mutation rate in respect to low level MSI, particularly at dinucleotide repeats, and by a higher frequency of LOH at chromosome 17p12, indicating that different genetic pathways are involved in the pathogenesis of gastric carcinomas arising in patients with and without a familial background of this disease.

Adult

Loss of heterozygosity and microsatellite instability in non-neoplastic mucosa from patients with chronic ulcerative colitis.

Microsatellite instability and allelic deletions of tumor suppressor genes have been observed frequently in tumors. Molecular pathogenesis of the development of dysplasia and carcinoma in ulcerative colitis is still unclear. In order to detect microsatellite alterations in ulcerative colitis, we analyzed loss of heterozygosity (LOH) and microsatellite instability (MI) on chromosomes 3, 6, 7, 12, and tumor suppressor gene loci, including p53, APC, and p16, of chronically inflamed, non-dysplastic epithelium after microdissection. Twelve of 13 (92%) cases showed LOH and/or MI at one or more loci. LOH at chromosome 3 and MI at chromosome 12 were observed in 50% and 62%, respectively. However, LOH at p53 and p16 was detected in only one case each. These results suggest that chronic inflammation may initiate microsatellite alteration, which subsequently transform ulcerative colitis to dysplasia or cancer. This finding provides information for the evaluation and treatment of patients with ulcerative colitis.

Journal Article