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M Oberholzer

Publications and source records attributed to M Oberholzer.

125 records · Page 7Linked to original sources

[Differentiation of lymphocyte populations in the blood of breast-cancer patients].

The number of T lymphocytes has been determined in the peripheral blood of 90 women (65 patients with breast cancer and 25 healthy controls) using a sheep-erythrocyte rosetting technique and a cytochemical method for intracellular localization of a nonspecific acid esterase. Both tests were in agreement in showing a significant depression of T-cell percentage in a group of patients with progressive disseminated breast cancer under hormonal and chemotherapeutic treatment. After radiotherapy a fall in T cells was observed only with the rosetting method. Possible reasons for this phenomenon are discussed.

Animals↗

Stereology of liver biopsies from healthy volunteers.

The stereological model and the base-line data of normal human liver needle biopsy-specimens are presented. Four reference systems were introduced: 1 cm3 of liver tissue, 1 cm3 of hepatocyte, 1 cm3 of hepatocytic cytoplasm and the volume of an average "mononuclear" hepatocyte. The sampling was done at three levels of magnification (1,000 X, 5,000 X and 10,000 X). A lobular differentiation was not considered. The baseline data show strikingly small variations (s.e. less than 10%) within the individual biopsy specimen and within the group of four biopsies. There is no principal difference between human beings presented here, rats, mice and dogs. Only the mean individual volume of human hepatocytes is clearly larger than in rodents. The problems and limitations of stereological work on liver biopsy specimens are discussed.

Animals↗

Digital imagery/telecytology. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Optical digital imaging and its related technologies have applications in cytopathology that encompass training and education, image analysis, diagnosis, report documentation and archiving, and telecommunications. Telecytology involves the use of telecommunications to transmit cytology images for the purposes of diagnosis, consultation or education. This working paper provides a mainly informational overview of optical digital imaging and summarizes current technologic resources and applications and some of the ethical and legal implications of the use of these new technologies in cytopathology. CONSENSUS POSITION: Computer hardware standards for optical digital imagery will continue to be driven mainly by commercial interests and nonmedical imperatives, but professional organizations can play a valuable role in developing recommendations or standards for digital image sampling, documentation, archiving, authenticity safeguards and teleconsultation protocols; in addressing patient confidentiality and ethical, legal and informed consent issues; and in providing support for quality assurance and standardization of digital image-based testing. There is some evidence that high levels of accuracy for telepathology diagnosis can be achieved using existing dynamic systems, which may also be applicable to telecytology consultation. Static systems for both telepathology and telecytology, which have the advantage of considerably lower cost, appear to have lower levels of accuracy. Laboratories that maintain digital image databases should adopt practices and protocols that ensure patient confidentiality. Individuals participating in telecommunication of digital images for diagnosis should be properly qualified, meet licensing requirements and use procedures that protect patient confidentiality. Such individuals should be cognizant of the limitations of the technology and employ quality assurance practices that ensure the validity and accuracy of each consultation. Even in an informal teleconsultation setting one should define the extent of participation and be mindful of potential malpractice liability. ONGOING ISSUES: Digital imagery applications will continue to present new opportunities and challenges. Position papers such as this are directed toward assisting the profession to stay informed and in control of these applications in the laboratory. Telecytology is an area in particular need of studies of good quality to provide data on factors affecting accuracy. New technologic approaches to addressing the issue of selective sampling in static image consultation are needed. The use of artificial intelligence software as an adjunct to enhance the accuracy and reproducibility of cytologic diagnosis of digital images in routine and consultation settings deserves to be pursued. Other telecytology-related issues that require clarification and the adoption of workable guidelines include interstate licensure and protocols to define malpractice liability.

Computer Communication Networks↗

Intralipid-based short-term total parenteral nutrition does not impair small intestinal mucosa-related cellular immune reactivity in the healthy rat.

BACKGROUND: The lipid component of total parenteral nutrition (TPN) has reportedly been associated with trophic effects on the intestinal mucosa and suppressive effects on the immune system. METHODS: We have challenged these hypotheses using a 7-day TPN rodent model comparing the effects of isocaloric, isonitrogenous lipid-based (TPN-lipid, 50% of calories as long-chain triacylglycerol) and carbohydrate-based TPN (TPN-CH, 100% of calories as carbohydrates) on mucosal morphology and immune function. Enterally fed animals were included to establish a baseline for immunologic read-outs. The study was performed in healthy, metabolically stable animals to avoid interference by septic or trauma-related stress factors. RESULTS: Both TPN regimens resulted in a significantly smaller weight gain (TPN-lipid, 29.8 +/- 4.0 g; TPN-CH, 30.3 +/- 4.4 g) compared with enterally fed reference animals (49.2 +/- 3.2 g; p = .007), with no difference in nitrogen balance between the TPN groups. Mucosal sucrase activity was significantly lower in both TPN groups (TPN-lipid, 8.8 +/- 1.0 x 10(-7) katal per gram (kat/g) of protein; CH: 11.9 +/- 1.6 x 10(-7) kat/g of protein) compared with enteral feeding (17.4 +/- 0.9 x 10(-7) kat/g of protein; ANOVA: p = .0007). Morphometric analysis of the small intestine revealed no differences between the two TPN groups although a significantly depressed villus height in the TPN-lipid group could be observed in comparison to enterally fed reference rats (TPN-lipid, 0.47 +/- 0.02; TPN-CH, 0.50 +/- 0.01; enteral, 0.56 +/- 0.02 mm; ANOVA: p = .0298). Light and electron microscopy revealed a normal surface architecture in all three groups of rats. Cellular immune reactivity was evaluated using a novel specific immunization protocol: animals were immunized against OVA 4 weeks before TPN. OVA-induced lymphoproliferative responses and phenotypic data from draining popliteal and mesenteric lymph nodes were evaluated after the different regimens. Results did not differ among the three groups. CONCLUSIONS: In healthy rodents, short-term lipid-based and carbohydrate-based TPN regimens lead to limited mucosal atrophy with preserved surface architecture compared with enteral feeding. However, peripheral and mesenteric cellular immune responsiveness after both TPN regimens remained comparable to enterally fed reference animals. Therefore, mesenteric and systemic cellular immune reactivity does not appear to be impaired by lipid-based or carbohydrate-based TPN.

Animals↗

Glutamine peptide-supplemented long-term total parenteral nutrition: effects on intracellular and extracellular amino acid patterns, nitrogen economy, and tissue morphology in growing rats.

Glutamine (GLN) is a nonessential amino acid that is not included in current regimens for parenteral nutrition because of its chemical instability. This study tested the hypothesis that GLN supplementation during long-term total parenteral nutrition (TPN) (3 weeks) would enhance GLN availability, thereby improving nitrogen economy and growth in a growing rat model: Standard TPN delivering 300 kcal/kg per day (lipid:carbohydrate = 1.1) including 2.1 g of nitrogen per kilogram per day in an all-in-one solution was compared with an isonitrogenous, isocaloric, and isovolemic TPN regimen with 0.29 g of nitrogen per kilogram per day substituted by GLN derived from the dipeptides glycyl-GLN and alanyl-GLN (TPN GLN). Enterally fed controls were included. Analysis was confined to nonbacteremic animals with negative blood culture, in which extracellular and intracellular amino acid concentrations including GLN, nitrogen balance, serum protein concentrations, growth, and histologic sections of liver and small-bowel mucosa (light and scanning electron microscopy) were evaluated. Hepatic intracellular GLN concentrations were significantly lower, in animals receiving GLN-free TPN (11.7 +/- 1.6 nmol/mg fat-free dry and solid tissue mass, n = 9) compared with both GLN-supplemented TPN (16.0 +/- 3.0, n = 7) and enteral feeding (18.2 +/- 1.8, n = 6) (p < .001). Corresponding results were found for intracellular GLN concentrations in skeletal muscle (TPN standard 12.5 +/- 3.1, TPN GLN 14.7 +/- 3.1, enteral control 17.3 +/- 2.3, p < .05), intestinal mucosa, and spleen as well as for plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

alpha-MSH receptor autoradiography on mouse and human melanoma tissue sections and biopsies.

MSH receptors and their binding characteristics of [125I]-labelled derivatives of alpha-MSH have been studied extensively on various mouse and human melanoma cell lines in culture. The aim of this study was to determine the binding characteristics of alpha-MSH radioligands to MSH receptors occurring in experimental mouse and human melanoma tumours as well as in human melanoma biopsies. For this reason, solid tumours were grown on experimental animals by inoculation of murine B16-F1 and human D10 and HBL melanoma cells. After excision and cryosectioning of the tumours, frozen tissue sections were incubated with [(125I)Tyr2]-alpha-MSH or [(125I)Tyr2,Nle4,D-Phe7]-alpha-MSH and specific alpha-MSH binding sites were visualized by subsequent autoradiography. The presence of increasing concentrations of unlabelled alpha-MSH during incubation with tracer led to a dose-dependent displacement of the radioligand. Quantitative analysis of the autoradiograms produced dissociation constants which were comparable with those obtained with cell binding assays: KD = 1.87 and 1.31 nmol/l for B16 tumours and cells, respectively; 0.32 and 0.33 nmol/l for D10, and 2.24 and 1.36 nmol/l for HBL tumours and cells, respectively. This indicates similar binding properties of alpha-MSH radioligands to both cultured melanoma cells and tissue sections of melanoma tumours from experimental animals. Similar binding characteristics were also observed with human melanoma tissue sections originating from biopsies of melanoma patients.

Animals↗

[Monocytes/macrophages in synovial tissue in chronic polyarthritis and arthrosis--differentiating from monoclonal antibodies].

Using monoclonal antibodies directed towards distinct cell surface antigens of the monocyte/macrophage lineage, we tried to disclose diagnostically relevant differences in the distribution pattern of monocytes and macrophages in cryostate sectioned synovial tissue samples from patients with rheumatoid arthritis and osteoarthrosis, psoriatic arthritis (n = 1) and a healthy control subject. As compared to osteoarthrosis, we found that in rheumatoid arthritis, accessory cells of the T- and B-cell immune response are pronounced in the basis areas of the superficial cell layers, indicating an active inflammatory process of immunological origin. Applying monoclonal antibodies specific for monocytes and immature macrophages of connective tissue, we confirmed the finding of an enhanced migration of those cells from the peripheral blood stream into the inflamed synovial tissue. Despite those findings, we were not able to demonstrate significant immuno-morphological differences between tissue from patients with rheumatoid arthritis and osteoarthrosis.

Adult↗

Stereology: a new quantitative morphological method to study epididymal function.

Stereology is a method to obtain quantitative information of structural changes at the light and electron microscopic level. The basic principles of stereology are outlined below. This paper shows how stereologic techniques can be used to obtain structural data from histologic and electron micrographs of intact tissue and cells. A stereologic model, which provides information on the structure of the epididymis has been developed for the rat epididymal head. The model consists of morphologically defined space and membrane compartments of the rat epididymal head and the principal cells. The alterations, induced in the principal cell of the epididymal head after long term hypophysectomy were studied by electron microscopy. The results presented are relative to a cubic centimeter of epididymal tissue, a cubic centimeter of principal cells and principal cell cytoplasm. An attempt to relate stereologic and biochemical data is shown.

Animals↗

Overview of quantitative methods in toxicologic pathology.

Today's stringent requirements for new drugs make it necessary to prove their safety by the use of ever more refined techniques, in particular methods to quantify morphologic findings to determine accurately, for example, the highest non-toxic dose in animal studies or to correlate morphological effects with other parameters. Increased cell proliferation due to subtle cytotoxicity can lead to epigenetic tumorigenicity, which can be recognized early by cytokinetic investigations using bromodeoxyuridine (BrdU) incorporation and/or proliferating cell nuclear antigen (PCNA) expression, or by malignancy-associated nuclear texture changes. Morphometric criteria are also used to increase diagnostic accuracy in experimental animal pathology. The various applications of morphometry in toxicopathology are reviewed, and examples illustrating these applications are presented, most of them unpublished.

Animals↗

Analysis of proliferative activity using Ki-67 on cervical precancerous lesions and the relationship to p53 expression.

Neoplastic cell growth rate and the p53 expression have been recently analysed in invasive cervical carcinoma. Samples of 20 specimens with normal cervical epithelium and 73 specimens of dysplasia and carcinoma in situ (CIS) were immunostained with monoclonal antibodies to p53 and Ki-67 to examine the interrelationship between p53, Ki-67 and HPV status in cervical intraepithelial neoplasm. The presence of HPV was assessed by in situ DNA hybridization. Of dysplasias and CIS 79% were HPV positive. The growth rate of neoplastic cells was significantly correlated to the histological grade and the HPV status. The highest proliferation was found in poorly differentiated HPV 16/18 positive precancerous lesions. The analysis of the p53 expression showed no difference between various histological grades. However, the p53 oncoprotein was expressed significantly lower in HPV 16/18 positive neoplasms. The assessment of neoplastic cell growth rate offers a potentially valuable approach to predicting biological behaviour in intraepithelial neoplasms.

Biomarkers, Tumor↗