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U Löhrs

Publications and source records attributed to U Löhrs.

At least 19 recordsLinked to original sources
PubMed1992

Analysis of proliferative activity in colorectal mucosa by immunohistochemical detection of proliferating cell nuclear antigen (PCNA). Methodological aspects and application to routine diagnostic material.

Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) has been suggested as a new approach for determining proliferative activity in paraffin-embedded tissue. In a prospective study PCNA immunostaining was performed in 284 colorectal biopsies using monoclonal antibodies 19F4 (Ogata et al. 1987) and PC10 (Waseem and Lane 1990) and compared with the Ki67 method. From each site three biopsies were taken and a variety of fixation regimens for frozen and paraffin-embedded samples tested. For frozen biopsies methanol fixation at -20 degrees C proved best. In paraffin sections PCNA could be detected after methacarn fixation as well as after controled fixation at 4 degrees C in 4% paraformaldehyde for 1 h and in most biopsies routinely fixed with 10% formalin. However, the latter fixation regimens revealed additional PCNA-positive cells in the normal superficial colonic mucosal epithelium. Although the percentage of cells positive for PCNA was generally lower than for Ki67, the rates correlated in a highly significant fashion, both in frozen methanol-fixed biopsies, and in paraformaldehyde-fixed paraffin-embedded samples. PCNA immunohistochemistry revealed a similar proliferative activity in different parts of the large bowel. A higher proliferative activity was found in inflamed mucosa, adenomas, carcinomas and even in normal mucosa from patients with colorectal neoplasms. In routinely fixed biopsies, the monoclonal antibody PC10 was superior to 19F4 because of considerably less background staining. However, in the routine material only a rough estimate of the proliferative activity was possible by PCNA immunohistochemistry using these antibodies, because unpredictable numbers of non-S-phase cells were also stained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

[In vivo and in vitro effects of GnRH analogs on ovarian Leydig cell tumor].

A 65-year old patient, suspected to be suffering from an androgen producing ovarian tumour, was treated preoperatively with the GnRH agonist triptorelin (500 micrograms/day s.c.) for 7 days. After an initial rise, gonadotrophin levels were suppressed under this treatment. The elevated serum testosterone concentrations were reduced by approx. 50% by the triptorelin injections. After the extirpation of the tumour (histologically a Leydig cell tumour of the ovary without signs of malignancy), primary cell cultures which secreted testosterone and androstenedione were prepared. Coincubation of the tumour cells with the GnRH agonist triptorelin had no effect on their androgen secretion. Treatment of the tumour cells with high concentrations (10(-5) M) of a GnRH antagonist, however, resulted in a 100% increase of their testosterone and androstenedione secretion. GnRH-binding sites of low affinity (Ka = 0.54 x 10(5) M-1) and high capacity (B max = 1364 x 10(-12) M/mg membrane protein) were identified in the tumour. These findings suggest that GnRH analogues might modify androgen secretion of sex-cord stromal tumours of the ovary via the suppression of endogenous gonadotrophin secretion and possibly also via direct effects on the tumour cells.

Aged↗
PubMed1991

DNA-ploidy and survival in gastric carcinomas: a flow-cytometric study.

In 125 gastric carcinomas the nuclear DNA content was determined by flow cytometry from formalin-fixed and paraffin-embedded tissue of surgical specimens. The carcinomas were of intestinal or mixed type (85), and diffuse type (40). DNA-aneuploidy was found in 46% of the intestinal type and in 42% of the mixed type, but only in 15% of the diffuse-type carcinomas (P less than 0.01). The total rate of DNA-aneuploidy was 34%. Carcinomas localized in the cardia were more frequently DNA-aneuploid than tumours in other localizations (P less than 0.01). DNA-aneuploid carcinomas had metastasized more frequently to regional lymph nodes (P less than 0.05) whereas no correlations with tumour stage and cytological/histological grade were detected. In 94 patients follow-up data were available. DNA-aneuploidy was associated with a statistically significant poorer prognosis when compared to DNA-diploid tumours only in advanced gastric carcinomas with lymph node metastases (P = 0.0488) and in the subgroup of advanced intestinal and mixed-type tumours (P = 0.0289).

Adenocarcinoma↗
PubMed1991

Osteoporosis in longstanding acromegaly: characteristic changes of vertebral trabecular architecture and bone matrix composition.

Although it is now 60 years after Erdheim's (1931) detailed description of vertebral alterations in severe acromegaly, it is still unclear whether osteoporosis is a consistent feature of acromegalic bone disease or not. We studied the vertebral trabecular bone of a 44-year-old woman who had suffered active acromegaly for more than 20 years, and compared it with 17 normal as well as 2 osteoporotic controls. Histomorphometry revealed a very low trabecular bone volume and thus documented the presence of osteoporosis. The mean trabecular plate thickness was strikingly increased in acromegaly (possibly caused in part by a low-dose fluoride treatment), whereas it was normal or reduced in the osteoporotic controls. The meticulous analysis showed islands of cartilaginous tissue in the core of the acromegalic trabeculae which were not present in any other sample. In these areas collagen II was detected by immunohistochemistry. Biochemical analysis revealed that collagen II accounted for 7% of the total collagenous matrix. The degree of hydroxylation of lysyl residues of collagen I was close to the average value of all control samples studied. Our data show that osteoporosis can occur in acromegaly and that it is characterized by unusual architectural and compositional features. These findings challenge the prevailing view that the matrix of osteoporotic bone always shows a normal composition.

Acromegaly↗
PubMed1991

Intratumoural heterogeneity of nuclear DNA-content and proliferation in clear cell type carcinomas of the kidney.

Clear celled renal carcinomas (n = 37) were investigated by flow cytometry for intratumoural heterogeneity in DNA-ploidy and proliferation (S-phase rate). Using gross sections of the tumours, 178 regions of interest were selected and excised from the paraffin blocks. Of the tumours examined 30% (n = 11) were DNA-diploid and 70% (n = 26) were DNA-aneuploid. In six tumours (16%) homogenous DNA-aneuploidy was detected, and in 20 others (54%) there was intratumoural heterogeneity of DNA-content with a blend of either DNA-diploid and DNA-aneuploid regions (n = 16; 43%) or different aneuploid stemlines (n = 4; 11%). DNA-aneuploidy was present both in areas of the tumours composed of clear cells and in regions containing cells with cytoplasmatic eosinophilia. However, DNA-aneuploidy was correlated in a statistically highly significant manner with the degree of cytoplasmatic eosinophilia and the nuclear grading of tumour cells. The results were confirmed by comparative analysis of fresh-frozen and paraffin-embedded material. The DNA-aneuploid portions of the tumours, and the regions with increased cytoplasmatic eosinophilia, proved to have significantly higher S-phase rates than DNA-diploid and clear tumour cells. These results agreed well with the immunohistochemically determined percentage of Ki-67 (proliferation associated)-antigen positive cells. Our findings indicate that tumour cells with increased eosinophilia in renal cell carcinomas are distinct from real clear cells by virtue of their higher rates of aneuploidy and proliferative activity. These cells might therefore be regarded as a subclass with a more aggressive biological behaviour.

Adenocarcinoma↗
PubMed1991

C-myc expression in early human placenta--a critical evaluation of its localization.

A tight association between the expression of the protooncogene c-myc and the proliferation of trophoblast in first trimester human placentae has been reported, supporting the view that c-myc is under close control of the cell cycle. However, this has not been verified in several other cells systems. Therefore we reexamined the exact localization of myc expression at the transcriptional and translational level in 20 first trimester and three term placentae. Myc mRNA and protein was sparse or absent at term but abundant in early gestation placentae. The proliferative cell columns and the villous cytotrophoblast contained the greatest amounts, revealing myc protein in around 60-70% of villous cytotrophoblast cells. Unexpectedly, a considerable fraction of the syncytiotrophoblast nuclei of early placentae (20%) also showed myc expression, and this was particularly evident on the protein level. The myc content estimated by immunohistochemistry decreased with increasing placental maturation. In addition, prominent myc expression was seen in decidual cells, suggesting a paracrine growth regulation of the gestational endometrium. Our findings do not support the notion that myc expression is closely cell cycle-dependent. On the contrary, it appears that in the human placenta, myc expression characterizes the phase of rapid organ development in the first trimester and is not restricted to the proliferative cytotrophoblast.

Alkaline Phosphatase↗
PubMed1991

Receptor-mediated processing of epidermal growth factor in the trophoblast of the human placenta.

The processing of epidermal growth factor (EGF) and its receptor in human trophoblast during the first trimester and at term was studied using biotin-labeled EGF, an anti-EGF receptor monoclonal antibody and immunohistochemistry. In chorionic villi incubated with EGF-biotin the ligand was first bound to specific receptors on the syncytial surface, which are in contact with the maternal blood. After 2-5 min in the early gestation placenta, EGF-biotin was found at the basal plasma membrane of the syncytium accompanied by a pronounced EGF receptor immunostaining. In contrast, in the term placenta, immunostaining of EGF-biotin as well as EGF receptors was pronounced in the syncytioplasma within 30-60 min following EGF stimulation; in addition, EGF-biotin was found in some syncytial nuclei. These immunostaining reactions were enhanced after lysosomal blockage by chloroquine. The results reveal a transsyncytial, receptor-mediated transfer of EGF from the maternal blood to the cytotrophoblast, the proliferating part of the trophoblast, in the first trimester placenta. However, in the term placenta, the EGF signal seems to be directed primarily to the syncytium, thus probably influencing differentiated functions. In conclusion, the trophoblast examplifies three possible pathways of EGF processing: 1. transcytotic transfer, 2. direct intracellular signalling followed by lysosomal degradation, and 3. nuclear binding.

Biological Transport↗
PubMed1991

Flow-cytometric analysis of the DNA-content in paraffin-embedded tissue from colorectal carcinomas and its prognostic significance.

The nuclear DNA content of 163 colorectal carcinomas was determined by flow-cytometry (FCM) on formalin-fixed, paraffin-embedded tissue. DNA-aneuploidy was found in 97 cases (59.5%), in which no statistically significant correlations with sex, mean age, tumour stage (Dukes and pTNM) and tumour grade were noted. The frequency of aneuploidy was significantly higher in patients less than 70 years of age (p less than 0.01) and in tumours localized in the left colon and rectum (p less than 0.002), irrespective of their stage. The tumours in which different areas could be analysed (n = 80) showed a heterogeneous DNA-ploidy pattern in 18%. Comparison of the DNA content in primary tumours and in lymph node metastases (n = 49) showed a difference in DNA-ploidy in 38% of the DNA-aneuploid tumours, but in only 6% of the DNA-diploid carcinomas (p less than 0.02). DNA-aneuploid carcinomas tended to show a higher rate of local recurrence and were associated with an unfavourable prognosis (p = 0.04) in those patients in which complete resection of their tumours was possible (n = 72). The significantly higher mortality of patients with DNA-aneuploid carcinomas of stage pT3, as well as those with Dukes stage A and B tumours indicates that DNA-aneuploidy may be a stage-independent additional risk factor in colorectal cancer.

Aged↗
PubMed1991

Proliferation of villous trophoblast of the human placenta in normal and abnormal pregnancies.

The proliferation of villous trophoblast in the human placenta was estimated throughout normal gestation and in term placentae from preeclamptic and smoking mothers by two different methods. These were: 1) labeling of DNA producing cells by bromodeoxyuridine (BrdU) followed by immunohistochemistry using a monoclonal anti-BrdU antibody, and 2) immunohistochemical identification of all proliferating cells by the monoclonal antibody Ki67. Both methods revealed comparable results. In uncomplicated pregnancies there was a remarkable decrease in the labeling indices from early gestation to term. This was the result of a diminution of the number of Langhans' cells, although the cell division rate within the Langhans' cell layer remained nearly constant throughout gestation. A prolongation of the cell cycle in the cytotrophoblast cells at term was indicated by an increase in the Ki67/BrdU ratio. Compared with normal term placentae, there was an increase in the trophoblast proliferation rate in preeclampsia, but not in placentae from smoking mothers. Moreover, the number of Langhans' cells was diminished in placentae from smokers. The results indicate that there are different pathogenetic mechanisms of placental impairment in preeclampsia and in maternal smoking. In preeclampsia an injury to the syncytiotrophoblast seems to lead to a repair hyperplasia of the cytotrophoblast, whereas in maternal smoking, there seems to be a direct toxic effect on the cytotrophoblastic cells.

Cell Division↗
PubMed1991

Venous thrombosis and pulmonary embolism. A study of 5039 autopsies.

The frequency and the localisation pattern of venous thrombosis and subsequent pulmonary embolism detected postmortem was studied by reviewing 5039 autopsy records from 1975 through 1980 and from 1987/88 of two university hospitals. The autopsy procedure was identical in both study periods. Thrombosis was documented overall in 34.2% with a slight increase from the first to the second series. Taking in account the cases of pulmonary embolism without detected source, the thrombosis rate was 42.6%. The rate of cases with thrombi in the vena cava superior system almost doubled (1975: 9.2%, 1987/88: 17.0%; p less than 0.05). Regarding the list of thrombus localisations the right internal jugular vein (16.9%) was second only to the left femoral vein (17.8%) in 1987/88. Pulmonary emboli were seen in 1500 of 5039 autopsies (29.8%); in 59.4% the source was found in the lower venous tree, in 12.6% in the upper venous tree. In 28.0% no source could be detected. In these cases we supposed a complete detachment of thrombi from the lower venous tree to be the most likely reason. In 628 of the 1500 cases (42.5%) pulmonary embolism was classified as fatal. Both rates, for total pulmonary embolism and for fatal thrombembolism showed a small, but significant decrease during the study period. In 8.3% (52/628) the source of fatal pulmonary emboli was situated in the upper venous tree including the right heart. This means that 10.2% (52/512) of all cases with isolated thrombosis in the vena cava superior system were associated with fatal pulmonary embolism. Venous thrombosis and pulmonary embolism are still frequent findings at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Autopsy↗
PubMed1990

Pituitary sarcoidosis.

A 66-year-old woman presenting with pituitary insufficiency was operated on for an intrasellar tumor. Surprisingly, this tumor, at first suspected to be a hormone-inactive pituitary adenoma, consisted in fact of sarcoid granulomatous tissue in the pituitary gland as found histologically. The morphological picture as seen in the cranial computed tomography was identical with that of an adenoma. This possibility had not previously been considered, although there had been an extracerebral manifestation of the sarcoidosis in the left ovary.

Adenoma↗
PubMed1990

Comparative investigations of regional lymph nodes and pseudocapsules after implantation of joint endoprostheses.

Morphological alterations of pseudocapsules and regional lymph nodes were studied by light and electron microscopy and by Laser Microprobe Mass Analysis (LAMMA). The tissue specimens originated from 32 autopsies of patients with hip joint endoprostheses (time in situ: 3 weeks - 15 years, average: 6 years) and two cases with knee joint endoprostheses. Characteristic changes of the lymph nodes as well as of the pseudocapsules consisted in an infiltration by monocytic histiocytes with various intracytoplasmatic wear particles. The foreign material consisted mainly of the components of bone cement: polymethylmethacrylate (PMMA) and zirconium oxide, to a lesser degree of polyethylene from the articulating surfaces. In two cases with special types of prostheses ceramic or metallic wear particles could be detected too. Most of the wear particles were found in the ipsilateral parailiac lymph nodes and in the paraaortic lymph nodes bilaterally. In the cases with mostly stable prostheses small amounts of wear particles were found in the lymph nodes as soon as 1.5 years after insertion and their number increased in all groups of lymph nodes after longer duration of the implant. The phagocytosing histiocytes showed degenerative changes. At present it is not clear, if the cell damage is caused by the amount of phagocytosed wear particles alone or if specific toxic effects of certain substances are of importance.

Granulation Tissue↗
PubMed1990

[Comparison of flow cytometric, static cytometry and tumor cytogenetic investigation results human renal cell carcinomas].

Published data about the frequency of DNA-aneuploidy of renal cell tumours show a great variation. The own study was performed to clarify whether this fact is due to methodological discrepancies or to intratumoural heterogeneity of DNA ploidy. The comparison of DNA ploidy assessed by flow cytometry (fresh and paraffin-embedded tissue) and static cytometry (paraffin-embedded tissue) in equivalent tumour regions showed identical results. 71% of clear cell renal carcinomas showed intratumoural heterogeneity of DNA ploidy. In 55% there was either a combination of diploid and aneuploid stem lines and/or a combination of different aneuploid stem lines ("heterogenous aneuploidy"). The rate of aneuploidy was found to be higher with increasing cytoplasmic eosinophilia of the clear cell renal carcinoma cells. Studies which address the prognostic significance of DNA ploidy of renal carcinomas should specifically investigate on the significance of heterogenous aneuploidy for prognosis.

Aneuploidy↗
PubMed1990

[Retrospective flow-cytometric analysis of the DNA content in colorectal carcinomas and the test of the prognostic significance of DNA ploidy].

The nuclear DNA content of 163 colorectal carcinomas was determined by flow-cytometry (FCM) on formalin-fixed and paraffin-embedded tissue. DNA-aneuploidy was found in 97 cases (59.5%), without correlation to sex, mean age, tumor-stage (DUKES and pTNM) and grading. The frequency of aneuploidy was statistically significantly higher in patients younger than 70 years of age (p less than 0.01) and in tumors localized in the left colon and rectum (p less than 0.002). The tumors in which different areas could be analyzed (n = 80) showed a heterogeneous DNA-ploidy pattern in 18%. The comparison of DNA-content in primaries and in lymph-node metastases (n = 49) resulted in a difference of DNA-ploidy in 38% of the DNA-aneuploid tumors, but only in 6% of the DNA-diploid carcinomas (p less than 0.02). Carcinomas with DNA-aneuploidy showed a trend to a higher rate of loco-regional recurrences, a higher S-phase fraction (13.5% +/- 5.9 vs. 8.1 +/- 7.0), and proved to be associated with a poorer prognosis (p = 0.04). The statistically significantly higher mortality of patients with DNA-aneuploid carcinomas in DUKES A and B stages indicates that DNA-aneuploidy could perhaps be regarded as a stage-independent additional risk factor.

Aged↗
PubMed1990

[Vertebral trabecular bone in various age groups and in osteoporosis-- morphometry and bone matrix biochemistry].

Vertebral trabecular bone was analysed by morphometry and bone matrix biochemistry. Trabecular bone volume (TBV) and mean trabecular plate thickness (MTPT) decreased with age. TBV was significantly correlated with MTPT and mean trabecular plate density (MTPD). The individual structure of trabecular bone could be described by both MTPT and MTPD together, but changes of these parameters, that were pathognomonic for osteopenia, were not found. By measuring TBV 3 cases of severe osteopenia were identified (TBV less than 2s of controls); 2 of them showed matrix abnormalities so far not described. In one case (a 67 year old woman without risk factors for osteoporosis) an abnormal high content of type III collagen was found, in the other case (a 44 year old woman with acromegaly) bone matrix analysis atypically revealed a significant fraction of type II collagen. Further studies will be needed to assess the pathogenetic or diagnostic importance of these new findings.

Adult↗