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Biomedical subjects

G Mikuz

Publications and source records attributed to G Mikuz.

At least 73 records · Page 4Linked to original sources
PubMed1992

Induction of arteriosclerosis in normocholesterolemic rabbits by immunization with heat shock protein 65.

Previous studies have established the presence of high numbers of activated T lymphocytes and "aberrant" expression of major histocompatibility complex class II antigens by endothelial and smooth muscle cells in human atherosclerotic lesions, implicating the involvement of a local cellular immune response. The identity of the antigen(s) eliciting this immune response, the extent of their effect, and the atherogenic stage at which they occur remain to be determined. In the present studies, 120 normocholesterolemic New Zealand White rabbits were immunized one or more times with various antigens, with or without adjuvants. The antigens and adjuvants included human or rabbit atherosclerotic lesion proteins, ovalbumin, Freund's complete and/or incomplete adjuvants, recombinant mycobacterial heat shock protein 65 (hsp65), and two hsp-free adjuvants, Ribi complete adjuvant and lipopeptide. In addition, some groups received a high-cholesterol diet. Sixteen weeks after the first immunization the animals were killed, and arteriosclerotic lesions in the intima of the aortic arch were found to have developed only in those animals immunized with antigenic preparations containing hsp, either in the form of whole mycobacteria or as purified recombinant hsp65, although their serum cholesterol levels were normal. No arteriosclerotic changes exceeding those of controls were found in the other groups, irrespective of the antigen used. Immunohistopathologic examination revealed that the lesions contained 20% T cells, 10-30% macrophages, and 10-40% smooth muscle cells. Analysis of the peripheral blood T-lymphocyte proliferative responses revealed that the occurrence of lesions was positively correlated with the presence of hsp65-reactive T cells, suggesting that hsp65 is involved in the induction of arteriosclerotic lesions. Furthermore, combined immunization with hsp-containing material and a cholesterol-rich diet provoked development of significantly more severe atherosclerosis and the appearance of characteristic foam cells. We conclude that an (auto)immune response to hsp may initiate the development of atherosclerosis and that a high blood cholesterol level is only one albeit a very important risk factor.

Animals↗
PubMed1992

A morphometric filter improves the diagnostic value of morphometric analyses of frozen histopathological sections from mammary tumours.

Frozen sections of 202 consecutive breast tumour cases were analyzed by morphometric quantitation of nuclear features. Nuclei were selected at random. Conventional light microscope examination of the paraffin-embedded specimens revealed 144 cases of cancer and 56 benign tumours. Using multivariate discriminant analysis of morphometric features, all but two of the benign cases and 79% of the malignant tumours were correctly classified. When a morphometrically based dynamic filter set to exclude 'non-diagnostic' nuclei was used, the correctly classified malignant cases rose to 86% Morphometry is a fast, reproducible and efficient method that can be used in conjunction with the histomorphological diagnosis of mammary frozen sections. The combination of systematic sampling and an objective dynamic filter may be a powerful approach to quantitative analyses of tumours from other sites. However, it is also likely that efficiency can be improved by combining nuclear morphometric features with structural, histochemical and molecular biological data. The combination of traditional histomorphological examination with quantitative information may well increase the diagnostic accuracy in individual patients.

Breast Neoplasms↗
PubMed1991

[Therapy-refractory fulminant meningococcal sepsis].

Two cases of the severe form of meningococcal infection are described. A 17-year-old girl and a (unrelated) 2-year-old boy suddenly developed fever and rigor. Several hours later petechiae of the skin were noted: they rapidly spread. On admission the girl was found to have a severe consumptive coagulopathy (prothrombin 24%, partial thromboplastin time 104 sec, fibrinogen 73 mg/dl, platelets 35,000/microliters). She died two-and-a-half hours after admission of treatment-resistant shock. The boy had at first only a low prothrombin value (39%), but later the other coagulation values also became abnormal. He died 16 hours after admission from the consumptive coagulopathy and profound anaemia (haemoglobin 7.4 g/dl, haematocrit 0.23). Neither patient had any clinical signs of meningitis. Isolation of Neisseria meningitidis from blood cultures confirmed the diagnosis.

Acute Disease↗
PubMed1991

Quantitative nuclear DNA content in fine needle aspirates of pancreatic cancer.

The quantitative nuclear DNA content of nuclei from fine needle aspirations from 70 patients with pancreatic cancer was measured using an image analyser system. Retrospective analysis of patients indicated that cases with tumour stemlines in the diploid region had the best chance for radical surgery (p less than 0.006) and the best probability of survival (p less than 0.0004). The prognosis for patients with tetraploid stemlines was intermediate and was poorest for patients with no stemlines in the diploid-tetraploid region. From those parameters assessed postoperatively, only the tumour stage added appreciable information on prognosis to the preoperative quantitative DNA content obtainable. Therefore, in patients with pancreatic cancer the quantitative DNA content should be taken into account in planning treatment and assessing prognosis. Furthermore, the quantitative DNA content may have a major role in stratification for further treatment trials.

Adult↗
PubMed1990

Silver stained nucleolar organizer region proteins (Ag-NORs) as a predictor of prognosis in colonic cancer.

Using a one-step silver nitrate staining technique, routinely processed tumour tissues of 49 carcinomas of the colon were investigated to demonstrate silver-stained nucleoli (Ag-nus) and argyrophilic proteins associated with the so-called nucleolar organizer regions (Ag-NORs). Patients with attempted curative resections and tumour stages Dukes' A, B, C1 and C2, with an uneventful follow-up period of at least 48 months (N = 17), showed a statistically significant (P = 0.0001) lower mean number of scattered Ag-NORs (3.04; SD: 1.08) compared to patients who developed metastases during their follow-up period (N = 15; 5.40; SD: 1.28), as well as to patients who underwent palliative surgical treatment (N = 17; 4.48; SD: 1.67). Mean numbers of scattered Ag-NORs per nucleus and staging of the tumour were strongly related (P = 0.0001) to cancer-specific survival. The results indicate that the evaluation of silver-stained particles according to their different distribution patterns is of great value with regard to the clinical outcome of colonic carcinoma and may even allow a more accurate prognostic assessment of these patients than the WHO grading system, UICC staging system, the so-called Jass-scoring system, and Dukes' classification.

Adult↗
PubMed1990

Nuclear DNA distribution pattern of the parenchymal cells in adenocarcinomas of the pancreas and in chronic pancreatitis. A study of archival specimens using both image and flow cytometry.

The nuclear DNA distribution pattern of the neoplastic parenchymal cells of 100 conventionally formalin-fixed and paraffin-embedded specimens from pancreatic adenocarcinomas and from 8 specimens of chronic pancreatitis was assessed by means of image cytometry. All material originated from pancreatic restrictions. Evaluable DNA histograms could be obtained for 77 carcinomas, and clinical data were available for 71 of these. In these 71 specimens, the nuclear DNA ploidy pattern was also investigated by means of flow cytometry. In 76 of the 77 cases, the image-cytometric DNA ploidy pattern obtained showed a "nondiploid" distribution with modal values as high as 8.5 c. In 21 cases, the neoplastic cells showed modal values in the "triploid" region. The analogous 71 flow-cytometric DNA histograms could only be evaluated in 50 cases because of excessively high amounts of background and/or excessively broad peaks. In 47 cases, the nuclear DNA histogram was nondiploid according to both techniques. The patients with carcinomas whose cell nuclei showed a triploid DNA distribution showed a significantly shorter survival time than those with tumor cell populations of nontriploid DNA distribution patterns. In the 8 specimens of chronic pancreatitis, the parenchymal cells were all equipped with nuclei showing diploid DNA distribution patterns.

Adenocarcinoma↗
PubMed1990

Cytomegalovirus pneumonitis in heart-lung transplant recipients: histopathology and clinicopathologic considerations.

Three cases of cytomegalovirus (CMV) pneumonitis in heart-lung transplant recipients are presented, and the clinical course and autopsy findings described. The patients survived transplantation for 15, 6, and 2 months, respectively. Cytomegalovirus pneumonitis was diagnosed between 5 and 12 weeks postoperatively, and was still detectable in two of the patients at postmortem examination. In one patient, at autopsy there was no further evidence of CMV pneumonitis 3 months after its onset. Instead we found widespread obliterative bronchiolitis (OB) and signs of acute pulmonary rejection. Early-stage OB was present together with CMV pneumonitis in the patient who had survived transplantation for 2 months. The cause of death in the remaining patient was a bacterial superinfection of the chronic CMV pneumonitis still present more than 1 year after its first manifestation. There were no signs of OB. The marked differences in the clinical course and histologic presentation of CMV pneumonitis in heart-lung transplant recipients and its high, but not uniform, association with OB emphasize the complex interrelations between viral infections and pulmonary rejection.

Adult↗
PubMed1990

[Plexus neuropathy: tumor infiltration or radiation damage].

Plexus neuropathies often occur in patients with breast cancer after varying periods following surgery and postoperative radiotherapy. In most cases this has been ascribed to radiation fibrosis. The attempt to arrive at a clinical diagnosis fails because of the similarity of symptoms in both cases namely pain and the absence of motoric and sensory reflexes. But a clear diagnosis is of fundamental importance for further treatment. Only a surgical intervention can verify the diagnosis. In this study, the results of operative findings are presented and compared with a second group of patients who had died of breast cancer having undergone surgery and radiotherapy. The findings brought a surprising fact to light: a considerably high percentage of all patients suffered from large scale tumour infiltration in the plexus. The morphology and histopathology of these lesions are described. Possible explanations are given for the difference in lesion patterns, so that a clinical diagnosis might be derived therefrom.

Adult↗
PubMed1990

Prognostic significance of tumor cell morphometry, histopathology, and clinical parameters in advanced ovarian carcinoma.

The prognostic value of clinicopathologic data and tumor cell morphometry was assessed in 49 consecutive patients with advanced epithelial ovarian carcinoma (Stage III-IV as defined by the International Federation of Gynaecologists and Obstetricians [FIGO]). Single-variant analysis proved that nuclear area at the 10th, 50th, and 90th percentiles and nuclear density were the strongest prognostic factors. To assess difference in prognostic influence between morphometric and clinicopathologic factors, Cox regression analysis was carried out and revealed nuclear density and age as prognostically significant (p less than 0.0003 and p less than 0.0004, respectively). Choice of chemotherapy, FIGO stage, histologic grade, and mitotic activity index (MAI) were not of additional prognostic importance. Objective measurement of morphometric factors is simple, highly reproducible, and adequate for routine work and promises to be of clinical value in therapeutic decision-making in advanced ovarian carcinoma.

Adult↗
PubMed1989

Expression of 7F7-antigen, a human adhesion molecule identical to intercellular adhesion molecule-1 (ICAM-1) in human carcinomas and their stromal fibroblasts.

The 7F7-antigen is a widespread 85-kDa membrane adherence molecule involved in heterotypic adhesion between PHA-blasts and fibroblasts. Immunofluorescence analysis of COS cells transfected with clone pICAM-I indicated that 7F7-antigen is identical with ICAM-I, the ligand for the contact molecule LFA-I. We have investigated the expression of ICAM-I on several human carcinomas. Tumor cells in most carcinomas, with the exception of squamous-cell carcinomas, expressed very little ICAM-I or none at all. In contrast, marked expression of this molecule was observed on fibrous tissue in the vicinity of carcinoma cells, its intensity correlating with lymphatic infiltration in these tumors. We also examined the expression of ICAM-I on carcinoma cell lines and its induction by treatment with interferon-gamma (IFN-gamma). The inducibility of ICAM-I expression on cultured fibroblasts by several lymphokines suggests that the expression of ICAM-I in the vicinity of carcinoma cells is effected by lymphokines produced by activated lymphocytes/macrophages within the tumor.

Antigens, Surface↗
PubMed1989

[Epidemiology of autopsy verified infection].

In a retrospective study of 35,220 autopsies performed from 1950 to 1984 in our department, septicaemia was found in 707 cases (2% of all autopsies). The incidence of pyaemia decreased after 1960, whereas that of septicaemia increased significantly. This increase was observed in surgical and medical departments due to patients suffering from neoplastic disease who died of septicaemia (40% of our cases). In the paediatric departments, however, mortality from septicaemia decreased slowly, but continuously. Age distribution revealed two peaks, one in infancy and one in patients older than 60 years. Over the past decade the mean age increased significantly (15 years on average). In blood cultures gram negative bacteria were found more often than gram positive strains.

Adult↗