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Biomedical subjects

M Oberholzer

Publications and source records attributed to M Oberholzer.

At least 73 records · Page 4Linked to original sources

Prognostic significance (relapse, non-relapse) of nuclear shape parameters in lymph node negative breast cancer.

A series of 15 postmenopausal patients with stage I invasive breast cancer (pT1-2, pNO, cMO) of uniform histologic type (ductal, NOS) was selected from the Basel Cancer Registry for retrospective analysis. A group of seven patients with a minimal disease-free survival of 9 years was compared to a group of eight patients with clinical and/or histopathological relapse within 8 years of mastectomy. Computer-assisted morphometry of cancer nuclei in routine histological material was used to investigate possible correlations of clinical outcome with nuclear size and shape parameters. Significant differences were found for certain shape descriptors by nonparametric statistical analysis. Stepwise discriminant analysis was applied to find the best combination of parameters separating the two prognostic groups. Application of the 'leaving one out method' showed correct classification in 6 of 8 recurrent cases and in all non-recurrent cases. The number of patients is small, therefore the results should be carefully interpreted.

Breast Neoplasms↗

[Cervical thymic cyst in childhood].

In three children (2, 4 and 10 years of age) a cervical thymic cyst was removed. We found multilocular cysts with xanthochromic luminal fluid covered with a fibrous capsule. Histological features are lymphatic follicles, partly atrophic, as well as regular thymic tissue with cortex, marrow and Hassall's corpuscles.

Child↗

Factor XII, plasma prekallikrein, alpha 2-macroglobulin and C1-inhibitor levels in renal allograft recipients during immunosuppression with cyclosporin A--sequential measurements over four months in 17 patients.

Factor XII clotting activity (F XII), plasma prekallikrein amidolytic activity (PK), alpha 2-Macroglobulin (alpha 2-M) and C1-Inhibitor (C1-Inh) antigens have been measured in 17 patients immediately before and sequentially for up to four months after kidney transplantation. Before transplantation mean F XII and PK levels were normal (99 +/- 27% and 102 +/- 21%, respectively, mean +/- S.D.) and alpha 2-M and C1-Inh levels were slightly elevated (115 +/- 55% and 129 +/- 32%, respectively, mean +/- S.D.). In the first two weeks after transplantation a significant decrease of F XII to 65 +/- 27%, of PK to 67 +/- 20% and of alpha 2-M to 88 +/- 42%, and a rise of C1-Inh to 201 +/- 44% (mean +/- S.D.) were observed (2 p less than 0.005). F XII levels four month after operation remained significantly (2 p less than 0.05) lower than preoperatively. PK and alpha 2-M values, however, were significantly higher (2 p less than 0.05) at four months as compared to the pretransplant period. Mean F XII levels in the 17 patients at various time points after transplantation correlated positively with PK, alpha 2-M and serum albumin and negatively with CyA level and dose and serum bilirubin. PK and alpha 2-M correlated positively with each other and albumin and negatively with creatinine, bilirubin and CyA (2 p less than 0.01). Whether CyA has a direct influence on production or consumption of F XII, PK, alpha 2-M and C1-Inh, or whether the changes merely reflect altered protein metabolism awaits further study.

Adult↗

A semiautomatic image analyzing system based on an APPLE II or IIe personal computer.

A new semiautomatic image analyzing system based on an APPLE II or IIe personal computer is described. The configurations of the hardware and software are extensively explained. The possibilities of applying the system are demonstrated by different examples taken from various projects in biological research and clinical pathology. The system is designed to fulfil the following requirements: (1) stepwise realization as a unit-by-unit system according to individual needs and interests, (2) acquisition and calculation of morphometric parameters, (3) provision of solutions for the greatest possible number of given problems in clinical and experimental pathology, (4) direct connection of the system to host computers for on-line data transfer and evaluation, and (5) optimum cost-benefit ratio by manifold application possibilities for the individual hardware and software elements. The advantages of the unit-by-unit system with personal computers outweigh in many respects the disadvantages (for example, increased file handling and limited capacity) in comparison with the closed automatized image evaluation system, particularly with regard to costs, flexibility and compatibility. The system is being further developed in collaboration with Kontron Bildanalyse GmbH, Eching/Munich, FRG.

Animals↗

The expression of subunits of human chorionic gonadotropin (hCG) by nontrophoblastic, nonendocrine, and endocrine tumors.

The value of the subunits of human chorionic gonadotropin (hCG) as tumor markers is controversial. The production of hCG-alpha and hCG-beta by 214 nontrophoblastic exocrine and by 416 endocrine tumors was analyzed by using immunocytochemical technics. hCG-alpha immunoreactivity was found in 131 of 416 endocrine and in 8 of 214 nonendocrine tumors. hCG-beta could not be visualized specifically with the use of two polyclonal antisera and one monoclonal antibody. The authors conclude that (1) hCG-alpha is neither a tissue nor a tumor-specific marker; (2) hCG-alpha is produced by a variable proportion (21-55%) of endocrine tumors arising in various organs but not by ileal carcinoids, paragangliomas, pheochromocytomas, nor Merkel cell tumors; (3) hCG-alpha is a marker of malignancy only in pancreatic endocrine tumors; and (4) hCG-beta is rarely, if ever, produced by tumors.

Carcinoid Tumor↗

Immunocytochemistry of pituitary tumors.

Pituitary tumors from 376 patients were investigated, using immunocytochemical techniques at the light and electron microscopic level, and autoradiography combined with immunocytochemistry for localizing somatostatin (SRIH) receptors. Prolactinomas, growth hormone-secreting adenomas causing acromegaly, and hormonally inactive adenomas were most frequently observed (153, 86, and 90 tumors, respectively). Among the latter, we could distinguish "alpha-only adenomas," many of which were oncocytomas. At the light and electron microscopic levels, cells containing (and presumably producing) simultaneously both prolactin and growth hormone, and cells containing exclusively either prolactin or growth hormone, could be demonstrated. In addition, a highly variable number and distribution of SRIH receptors could be shown in tumors secreting prolactin, growth hormone, and in tumors not associated with symptoms caused by inappropriate hormone secretion. The systematic combination of clinical, radiological, and biological techniques has currently brought great progress in the behavior and therapeutic concepts of pituitary lesions, and promises new achievements in the near future.

Adenoma↗

Morphometry and immunocytochemistry.

The use of morphometry (and stereology), especially in conjunction with immunocytochemistry, in surgical and experimental pathology is reviewed. The combined use of morphometry and immunocytochemistry permits the study of secretory products and the distinction between cells that produce them, e.g., as in the pancreas. Several examples to illustrate the application of immunocytochemical techniques in morphometry are presented. For example, using this approach on the pancreas, it was shown that not only B cells, but also A and D cells, seem to undergo pathologic changes in a prediabetic organism. Since morphologic alterations may be distributional as well as quantitative, a model for the assessment and statistical evaluation of the distribution of objects within an area is discussed. Similar procedures were used to analyze the distribution of cytochrome P-450 molecules along intracellular membranes; however, special labeling techniques were necessary for this quantification in the electron microscope. Immunoenzyme cytochemically stained secretions can also be studied morphometrically, and microdensitometry and microfluorometry can also be used to quantify immunocytochemical reactions, as is shown in the analysis of the intralobular distribution of NADPH-cytochrome P-450 reductase in the rat liver. Finally, the BIVAS semiautomatic system for morphometric measurements, developed at the Department of Pathology of the University of Basel, is briefly described.

Animals↗

Analysis of object clustering.

Objects of a given type lie on a plane or in a thin layer. In the analysis of the arrangement of such objects, the question may arise as to whether these objects form clusters or whether they are randomly distributed. This question can be answered by the calculation of the coefficient of dispersion (CD) of the objects. Some statistical properties of this coefficient, i.e., its sensitivity and its chi-square approximation, are analyzed in this paper. The proposed approach for calculating sensitivity is a mathematical simulation that is not generally applicable but is valid in various biologic applications. Assuming that the objects are much smaller than the expected clusters and that no knowledge exists about interactions among the objects or between the objects and their surroundings, the objects can be assumed to be distributed randomly on the plane. Such situations may occur in various fields, i.e., biology, sociology, archaeology and ecology. The authors have applied this approach successfully in investigating the densities of T-cell lymphocytes in renal transplants treated with Cyclosporin A or conventional immunosuppressive therapy.

Computer Simulation↗

Evaluation of shape descriptors for the morphometric analysis of cell nuclei.

A series of shape descriptors were developed for the morphometrical analysis of cell nuclei. These included five descriptors measuring ellipticity, two measuring concavity, and one measuring the bending energy of a contour. These different shape descriptors were compared using a test sample of 1800 contours of cell nuclei.

Cell Nucleus↗

Morphometry of bone. Are parameters from the iliac crest reliable indicators of renal-insufficiency osteopathy?

Bone samples from 25 autopsy cases with chronic renal insufficiency were analyzed stereologically. The findings in the iliac crest were found to be representative of those of the rib, femur condyle and lumbar vertebra for the following stereologic parameters: volume of osteoid seems related to total bone volume [VV(OID/BONE)], surface of osteoid seams related to total bone volume [SV(OID/BONE)] and surface of osteoid seams in relation to trabecular surface [SS(OID/TRAB)]. In addition, the value of various stereologic parameters for the classification of osteopathies was checked.

Aged↗

Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited.

The present review draws attention to the diversity of islet lesions seen in human type 1 and type 2 diabetes. This heterogeneity of islet changes is best demonstrated by immunocytochemistry. In type 1 diabetes the endocrine pancreas is characterized by selective loss of B cells, which most likely results from a slowly acting autoimmune process depending on the presence of both genetic and environmental factors. The process starts years before overt diabetes develops and manifests when the B-cell volume is reduced by about 80%. In type 2 diabetes B cells are always present, regardless of the duration and severity of the disease, but lack any signs of functional activity. This reflects a secretory defect of the B cells which obviously becomes evident under the conditions of obesity, hyperinsulinism and insulin resistance. Obese but non-diabetic subjects show, in parallel to their hyperinsulinism, an increased B cell volume, suggesting that under prediabetic conditions the B cells have still the capacity to respond to increased functional demands by enhanced proliferation. In manifest diabetes the B cells have lost their proliferative potential. Whether this is due to an inherent defect or the consequence of a functional disturbance, is not clear. The development of islet amyloidosis most likely represents an associated functional abnormality of the B cell.

Autoimmune Diseases↗

Stereology in the extraction of information from images.

Some important aspects for information extraction by stereology from images in surgical and experimental pathology are discussed. The relationship between stereology and morphometry is briefly discussed, with the most important conditions for stereologic analysis in pathology pointed out. The possibilities, limits and problems inherent in stereologic and morphometric analysis in pathology are explained in two examples: so-called "small airways disease" and tight junctions of hepatocytes during physiologic choleresis.

Adult↗

[Criteria for hemostasis in kidney transplant patients. Comparison of patients undergoing immunosuppression with cyclosporin and azathioprine steroids].

Studies on one-year function conducted by the European Multicenter Trial showed that, after renal allograft transplantation, bleeding complications were only found in patients treated with cyclosporin as compared with those treated with azathioprin/steroids. To investigate a possible relationship between the bleeding tendency and the cyclosporin treatment, 18 parameters of hemostasis were studied in 11 patients, 6 of whom received cyclosporin A and the other 5 conventional treatment with azathioprin/steroids. Bleeding tendency could not be related to any specific coagulation parameter. Of interest is that clot retraction was significantly lower in the cyclosporin group (88 +/- 9% vs. 125 +/- 10%). Considering the fact that the skin bleeding time according to Ivy was normal in all patients, the clinical significance of the lower levels of the clot retraction appears to be minor. Discriminant analysis showed that these significantly lower clot retraction values could not be related to the lower platelet count levels in platelet rich plasma (205 000 +/- 85 000/mm3 vs. 280 000 +/- 67 000/mm3) but were associated with cyclosporin A treatment. All factor-VIII related activities were elevated in both groups. The main difference between the cyclosporin group and the conventionally treated group was significantly elevated levels of factor VIII procoagulant antigen (VIII: CAg) (cyclosporin A treated group: VIII: CAg 435 +/- 145%, conventionally treated group: VIII: CAg 215 +/- 99%). These results suggest hypercoagulability rather than bleeding tendency under cyclosporin treatment.

Adult↗

Quantitative analysis of ACTH-immunoreactive cells in the anterior pituitary of young spontaneously hypertensive and normotensive rats.

ACTH-immunoreactive cells in the anterior pituitary of 4-week-old spontaneously hypertensive rats (SHR) were studied with immunocytochemical and morphometric techniques. The results were compared with data from age-matched normotensive Wistar-Kyoto rats (WKY). No significant differences were found in volume density and average size of ACTH-immunoreactive cells between these two strains. However, SHR showed a significantly larger anterior lobe (2 P less than 0.01) than WKY, indicating that the total number of ACTH-immunoreactive cells in the anterior pituitary is greater in SHR than in WKY. These data are in agreement with radioimmunological determinations showing a significantly elevated content (2P less than 0.01) but only a moderately higher concentration (0.05 less than 2P less than 0.10) of ACTH in the anterior pituitary of SHR as compared to WKY. The present results suggest an enhanced availability of ACTH in the anterior pituitary of 4-week-old SHR, a fact which could explain the markedly enhanced stress-induced release of ACTH previously found in these animals. This study further supports the hypothesis that, among other factors, an instability of the hypothalamo-pituitary-adrenal axis may contribute to the development of genetically programmed hypertension.

Adrenocorticotropic Hormone↗

Morphometric evidence for a striking B-cell reduction at the clinical onset of type 1 diabetes.

The distribution and volume of the pancreatic endocrine cells were studied in a case of type 1 diabetes with a duration of approximately 7 days. Immunocytochemical techniques combined with morphometry were used. The PP-cell rich lobe, making up about 10% of the total pancreatic volume, was not included in this study. The volume density and the absolute volume of the B-cells was found to be reduced to about one third to one seventh of the values determined in four controls of similar age and/or pancreatic volume. The A-cell volume was also diminished whereas the D- and PP-cell volume remained constant. As B-cell necroses could not be detected and insulitis was in the initial stages of development it is concluded that the destruction of B-cells proceeds slowly in type 1 diabetes. In the majority of cases it probably starts years before the clinical onset of the disease.

Cell Count↗