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Biomedical subjects

J Rüschoff

Publications and source records attributed to J Rüschoff.

At least 109 records · Page 6Linked to original sources

SO2-induced enhancement of inhalative allergic sensitization: inhibition by anti-inflammatory treatment.

Epidemiological studies have shown a relationship between air pollution and allergic airway disease. In a previous study we have found that exposure to SO2 enhances allergic sensitization to inhaled ovalbumin (OA) in the guinea pig. We have now investigated the influence of pre-treatment with anti-inflammatory drugs on SO2-induced enhancement of allergic sensitization in this model. Four groups of 6 guinea pigs each were exposed to 5 ppm SO2 on 5 consecutive days over 8 h per day with intermittent inhalation of OA, while the air-control group was exposed to clean air and OA. During the period of SO2 exposure and sensitization three experimental groups were treated with indomethacin (group I), methylprednisolone (group M) and nebulized nedocromil sodium (group N), while the control group remained untreated. Guinea pigs were investigated for sensitization to OA by specific bronchial provocation tests using body plethysmographic measurement of compressed air (CA) and by measurement of specific antibody response in serum. While in the SO2-exposed control group 5 of 6 animals reacted to specific bronchial provocation testing (CA median 0.15 ml, range 0-0.175 ml), only 1 animal was sensitized in group M (CA 0 ml, 0-0.125, p < 0.05), whereas no bronchial reactions were seen in groups I and N (CA 0 ml, 0-0.05, p < 0.025). Specific IgG antibody titres increased in the control group (median 43 EU-->85 EU), but not in the treatment groups (medians group I 35 EU-->35 EU, group M 30-->35 EU, group N 64-->50 EU).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

[Nucleolus organizer regions in pathomorphologic tumor diagnosis].

Morphology and biological behaviour of tumours are closely related to each other and are the main objects of diagnostic tumour pathology. Anaplasia, for example, a well-known cytomorphological criterion of malignancy, is however only an indirect sign of impaired cellular growth control mechanisms. Nowadays, it is a goal of cancer research to investigate these regulatory processes in order to elucidate new diagnostic criteria of malignancy. Silver staining of nucleolar organizer regions (AgNORs) basically meets this new concept. NORs (rDNA) encode for ribosomal RNA and are thus of central importance for the protein synthesis of a cell. Silver stains NOR associated proteins and indicates activated rDNA. Therefore, AgNOR staining covers the proliferative potential of a given cell or a tumour respectively. A prerequisite of reliable application of the AgNOR method to diagnostic tumour pathology is standardization of the technique, which should be based upon scientific results obtained by basic research. Accordingly, in interphasic cells AgNORs are primarily substructures of nucleoli corresponding to the fibrillar centers at the ultrastructural level. This has been shown to be an important criterion to determine the quality of the silver staining reaction. Most artifacts result from inadequate tissue preservation (fixation), unspecific argyrophilic structures and the staining procedure itself. They should either be excluded or--when ever possible--controlled by a proper staining technique, i.e. adjustment to the stainability of every individual specimen. In this respect, digital image analysis proved to be a useful tool. The mean size of AgNORs in small lymphocytes of the same tissue sample is an equivalent of the argyrophilia of a given histological and cytological specimen (internal staining standard). By use of such a standardized staining technique a high diagnostic accuracy is achieved. The proliferative potential of a cell or a tumour can be determined by number, size, staining intensity and distribution of the silver stained dots. In histological tissue sections the quotient of the mean number of AgNORs/cell and the mean area of one AgNOR dot/cell has been shown to be a very sensitive diagnostic parameter. In cytological specimens determination of the total silver stained area per cell is superior to counting of AgNORs simply by eye. Normal and malignant tissue can reliably be discriminated by these morphometric values. In addition, the malignancy potential of the different preneoplastic lesions, e.g. of the urinary bladder, can precisely be described. Flat urothelial lesions with moderate cytological atypia (D2) exhibit AgNOR values in the range of well differentiated papillary carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)

Biomarkers, Tumor↗

Application of the AgNOR technique to neurooncology.

The silver staining of interphase nucleolar organizer regions (NORs) is a recently developed method to measure cell proliferation in tissue specimens. The major silver staining protein is nucleolin, a 92 kd nucleolar protein, which probably controls rDNA transcription. Nucleolin itself is under control of p34cdc2 kinase, which is a subunit of M phase kinase. The specific silver staining of NORs measures ribosomal gene activity and is therefore useful in measuring cell proliferation via nucleolar biosynthetic activity. Although human tumors of different malignancy grades usually can be distinguished by their AgNOR number, there is considerable overlap between different grades which significantly hampers their use in individual cases. For routine application of the AgNOR technique in histopathology we propose a standardised staining protocol with use of internal control cells and the use of image analysis for AgNOR enumeration.

Animals↗

Lymph node counts in the upper abdomen: anatomical basis for lymphadenectomy in gastric cancer.

The number of regional lymph nodes was determined in sites relevant to lymphadenectomy in gastric cancer in 30 cadavers. Tissue was cleared by dissolving fatty tissue, thus making lymph nodes with a diameter of at least 1 mm visible. All lymph node stations indicated by the Japanese Research Society for Gastric Cancer were studied. In stations 1-11 (corresponding with R2 resection) an average of 27 nodes (range 17-44 nodes) was found, whereas stations 1-16 (corresponding with R3 resection) showed an average of 43 nodes (range 25-64 nodes). These values are higher than those usually obtained from lymphadenectomy for gastric cancer. Striking individual differences in the total number of lymph nodes and the number of single stations was observed. The number of lymph nodes in these investigations are the normal anatomical values and serve as quality control of lymph node dissection in gastric carcinoma.

Adult↗

Reduction in HLA-DR antigen density on alveolar macrophages of smokers.

The expression of HLA class II genes is essential to the antigen-presenting function of monocytes and macrophages. With a new cytofluorometric method of single-cell analysis we investigated the density of HLA-DR antigen expression on alveolar macrophages (AM) of smokers. Although all AM of nonsmokers (100 +/- 1%) expressed HLA-DR antigens, only 79 +/- 12% of AM from smokers showed positive findings (p less than 0.001). Furthermore, the antigen density of those cells expressing this antigen was significantly reduced in smokers (p less than 0.001). The defective expression of class II genes on AM of smokers might contribute to the impaired antigen-presenting function found by some previous investigators.

Antibodies, Monoclonal↗

Chromosome numbers and DNA-content in intracerebrally transplanted experimental gliomas.

Serially transplanted experimental tumors of the central and peripheral nervous system can be used as models to investigate open questions in human neurooncology. Altered susceptibility of higher passages to chemotherapy might be correlated with chromosome number and DNA-content variations which would be partly expressed as changes in proliferation behaviour. Karyotypes therefore were analysed in the 73rd to 90th generations of transplanted experimental gliomas. Wide variation of chromosome number was observed; 2 major types of distribution occurred, the one presenting with, the other without stemlines. Large chromosomes # 1 and # 4 were often monosomic, while small chromosomes of ## 8 to 20 were increased up to the fivefold. Lines with prominent and few markers were observed. On the whole, cells of the proliferating pool of the tumor had to be considered as hypotetraploid. Comparison of chromosome numbers and DNA content gave good correlation; differences between the 2 were explained by the fact that only the number of chromosomes was taken into account, regardless of whether small or large chromosomes were lacking or in excess. When intracerebrally transplanted tumors had been previously treated by administration of BCNU, the DNA content was altered, indicating an increased share of diploid cells in the proliferation pool. Results are at variance with earlier findings in tissue cultures of directly induced malignant gliomas and neurinomas in rats. The findings in transplanted tumors can be interpreted as a result of increased malignancy in transplantation tumors, documented by rapid growth in the animal and dedifferentiated histologic morphology.

Animals↗

[Sex cord stromal tumor with annular tubules in a sterility patient].

We report on the case of a 24 year old patient under medical treatment, because of sterility. The diagnosis of a rare sex cord tumour with annular tubules of the ovary before pregnancy, was followed by observation during this time and finally controlled after delivery by a sphenoidal excision from both ovaries. The influence of this disease on fertility and pregnancy and the influence of pregnancy on the tumour with its therapeutical consequences, will be discussed with reference to the current literature. The tumor is no reason for sterility. During pregnancy, an operative intervention may be inevitable. The histological status seems to be unchanged during pregnancy.

Adult↗

Cell proliferation in intracranial tumours: selective silver staining of nucleolar organizer regions (AgNORs). Application to surgical and experimental neuro-oncology.

A novel tool in diagnostic and experimental pathology, the AgNOR-technique, which consists of visualization of ribosomal gene activity by selective silver staining, was applied to 144 cytological specimens of human tumours of the nervous system. The number of silver-stained nucleolar organizer regions (AgNORs) was correlated with the biological behaviour of the tumours investigated; low AgNOR number were observed in benign neoplasms such as meningiomas and schwannomas and higher AgNOR numbers in glioblastomas and metastases. The mean AgNOR number per cell was 3.15 in astrocytomas, 4.5 in anaplastic astrocytomas and 5.86 in glioblastoma multiforme. Benign and malignant lesions showed different distribution patterns of AgNORs, with few but centrally located AgNORs in benign, and multiple but scattered AgNORs in malignant tumours. AgNOR number per cell and AgNOR area revealed an inverse relationship (correlation coefficient -0.15, linear regression). In addition to the human tumours, two N-nitroso-N-ethyl-urea (NEU) induced tumors in BD-IX rats a mixed glioma (G-XIII) and a malignant schwannoma (N-XII), were investigated. Twelve G-XIII gliomas revealed homogenous AgNOR-counts (standard error of the mean less than 10%), with absolute values between the values obtained for human glioblastomas and metastases. Seven N-XIII subcutaneously transplanted schwannomas revealed higher AgNOR values than human schwannomas, but lower than experimental gliomas. It is concluded that the AgNOR method, as a technique for visualization of ribosomal gene activity, is valuable for assessing proliferative activity and malignancy in both diagnostic and experimental neuropathology.

Animals↗

Silver-stained structures in prostatic carcinoma: evaluation of diagnostic and prognostic relevance by automated image analysis.

The comparison of the diagnostic and prognostic significance of histology, immunohistochemical parameters (PSA, PSP), and silver-stained nucleolar organizer regions (AgNORs) was estimated in paraffin sections taken of 63 prostatic carcinomas prior to therapy. AgNORs were visualized with a one-step silver staining technique with the appropiate staining time determined by preliminary staining-time series. The mean AgNOR number per cell (n) and the mean AgNOR area per silver-stained dot (A) were determined by means of an automatic image analysis system. Thereby prostatic carcinomas exhibited multiple small AgNORs within their nuclei (n = 4.7, A = 0.09 micron 2), whereas benign prostatic epithelium showed few but large silver-stained particles (n = 1.8, A = 0.27 micron 2; p less than 0.001). This relationship was then calculated as a quotient of AgNOR number and area (NQ = n/A) which provided additional information for the diagnosis of malignancy as well as survival. Univariate survival analysis disclosed a set of four variables predicting death from prostatic cancer; cribriform growth pattern, AgNOR quotient, histological grade, and PSA immunoreactivity. Of these parameters, immunoreactivity of PSA failed to prove its prognostic significance in multivariate survival analysis (Cox model). No relation to prognosis was found for the number as well as the area of AgNORs alone. Therefore, image analysis proved to be a prerequisit for the feasibility of this promising technique by providing objective and reproducible results.

Acid Phosphatase↗

[Ultrasonic diagnosis in suspected acute appendicitis: probable or certain indications for surgery?].

The diagnostic accuracy and the clinical impact of routine ultrasonography performed by 4 surgeons, were prospectively studied in 366 unselected patients admitted for suspected acute appendicitis. Clinical and sonographic findings on admission were correlated with laparotomy findings, pathological outcome and clinical as well as follow-up data. The overall sensitivity, specificity and accuracy of the clinical diagnosis of acute appendicitis were 55.3%, 94.6% and 84.2% respectively (positive predictive value (PPV) 75.8%, negative predictive value (NPV) 87.3%). Ultrasound enabled visualization of the disease in 67 of 85 (prevalence 23.3%) patients with a histologically confirmed acute appendicitis; false positive results were recorded in 7 cases (sensitivity 78.8%, specificity 97.5%, accuracy 93.1%, PPV 90.5%, NPV 93.8%). Ultrasound was particularly useful in patients presenting with equivocal or highly unsuspective signs of acute appendicitis: of 38 patients with an acute appendicitis in this group ultrasonography enabled to make the diagnosis in 26. The combined approach of clinical evaluation and routine ultrasonography markedly improved the diagnostic accuracy (sensitivity 85.9%, specificity 96.4%, accuracy 94%) and substantially reduced the negative laparotomy rate (7.9%) in patients with suspected acute appendicitis. It is concluded, that ultrasonographic evaluation of the patient with suspected acute appendicitis performed by surgeons is of great assistance in surgical practice.

Abdomen, Acute↗

A cytofluorometric method to quantify membrane antigens on individual alveolar macrophages.

An immunofluorescence method for assaying membrane-bound antigens on individual alveolar macrophages (AM) collected by bronchoalveolar lavage (BAL) is described. Cells were labelled with FITC-conjugated anti-HLA-DR antibodies in a single (direct) step. Quantification of the fluorescence was performed by computer-assisted cytophotometry. Alveolar macrophages, especially when obtained from cigarette smokers, exhibited an autofluorescence which interfered with the measurement of specific fluorescence. The specific fluorescence was calculated by determination of total fluorescence in the wave-length optimal for FITC and the non-specific fluorescence in a different wavelength during a second measurement. Specificity and reproducibility testing confirmed the reliability of the method.

Analysis of Variance↗

Evaluation of nucleolus organizer regions (NORs) by automatic image analysis: a contribution to standardization.

This study summarizes our experiences with the silver staining of nucleolus organizer regions (AgNORs) in a total of 580 tumours from ten different tissues. In contrast to other investigators, we made use of automatic image analysis for the evaluation of AgNORs. This provided good reproducibility as determined by the standard cumulative means technique and intra-observer (r1) and inter-observer (r2) agreement in 30 benign (r1 = 0.83-0.95, r2 = 0.76-0.92) and 50 malignant tissue samples (r1 = 0.72-0.85, r2 = 0.51-0.78). By using a series of staining times on sections from 30 tissue blocks taken from the ten types of tissue investigated, considerable variation in the argyrophilic staining of NORs in different tissues and in different blocks from one tumour was shown. The mean AgNOR area of resting lymphocytes or connective tissue cells within tissue blocks of the same organ system varied up to four-fold, even though identical staining times had been used. The most suitable silver reaction time which rendered a good diagnostic difference in the AgNOR content of benign and malignant tissue ranged, for example, in the breast cancer specimens, from 23 to 35 min. We therefore conclude that the staining time has to be adjusted to the individual silver-binding characteristics of each tissue block or even each section. The use of internal staining standards like lymphocytes or connective tissue cells in the same tissue section is mandatory. This, in turn, is most precisely controlled by morphometry.

Humans↗

Assessment of nucleolar organizer regions by automatic image analysis in breast cancer: correlation with DNA content, proliferation rate, receptor status and histopathological grading.

The value of automatic image analysis in the investigation of nucleolus regions (AgNOR) has been examined in tissue sections of 52 malignant and 30 benign breast lesions. Determination of the AgNOR number per cell alone revealed a considerable overlap between benign (range 1.2-3.8) and malignant specimens (range 1.5-16.2). They differed however, highly significantly (P less than 0.001) in their AgNOR sizes. In benign breast disorders the mean AgNOR area per tumour ranged from 0.22 microns2 to 1.07 microns2 (mean 0.39 microns2), whereas in carcinomas AgNOR sites ranged from 0.05 microns2 to 0.22 microns2 (mean 0.09 microns2). AgNOR counts showed a good correlation with histopathological grade (P less than 0.05), aneuploidy (P less than 0.01), proliferation rate as determined by Ki67 immunostaining (P less than 0.01), as well as oestrogen and progesterone receptor content (P less than 0.01). Image analysis proved to be advantageous over AgNOR counting alone as it facilitated the standardization of the AgNOR technique itself and thus, significantly improved its diagnostic specifity.

Breast Neoplasms↗

Proliferative potential of human brain tumours as assessed by nucleolar organizer regions (AgNORs) and Ki67-immunoreactivity.

Two proliferation markers, silver stained nucleolar organizer regions (AgNOR) and immunoreactivity with Ki-67, were used to assess the proliferative activity in 80 smear preparations from neurosurgically removed intracranial tumours. These included 45 gliomas, 18 meningiomas, 8 metastases and 9 others. We found a remarkably close correlation between the results obtained with both methods. Increasing malignancy, as determined by conventional grading, was paralleled by an increase in the growth fraction and the number of nucleolar organizer regions. Linear regression analysis yielded the following equation: AgNORs/cell = 0.35 x L1 (Ki-67) + 3.24, with a correlation coefficient of rs = 0.53 (Spearman rank correlation test, p less than 0.0001). Thus, both the Ki-67 L1 and the AgNOR technique appear suitable for estimating the proliferative potential in smear preparations of human intracranial neoplasms. The AgNOR technique may be particularly useful for application to stereotaxic biopsies since it can easily be performed on minute tumour samples.

Antigens, Surface↗

Prognostic significance of nucleolar organizing regions (NORs) in carcinomas of the sigmoid colon and rectum.

The prognostic significance of silver-binding nucleolar organizing regions (AgNORs) has been evaluated in tissue sections of biopsies taken from 70 primary adenocarcinomas of the colon sigmoid (n = 25) and rectum (n = 45) prior to their curative resection. A significant correlation between five-year survival rate and the mean AgNOR number per tumour cell (p less than 0.001) and the mean size of silver stained dots (p less than 0.05) was found according to the univariate Kaplan-Meier survival analysis. There was no significant relationship between AgNOR content and grade of malignancy, pT categories or pN categories. Multivariate survival analysis of covariates (Cox regression model) revealed a set of five variables that significantly influenced the patients' outcome: pN categories, AgNOR content, pT categories, maximum grade of malignancy and number of inflammatory cells. From the clinical and pathological parameters studied, pN and pT categories as well as the mean AgNOR number were the most important variables predicting death from colorectal carcinoma. Since the analysis of AgNORs can be performed on routinely processed paraffin-embedded tissue, this method may be of potential use in pretherapeutic assessment of the biologic aggressiveness of the disease.

Adenocarcinoma↗