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D Ofner

Publications and source records attributed to D Ofner.

At least 73 records · Page 4Linked to original sources
PubMed1994

Wet autoclave pretreatment improves the visualization of silver-stained nucleolar organizer-region-associated proteins in routinely formalin-fixed and paraffin-embedded tissues.

This study describes the effect of wet autoclave pretreatment of routinely formalin-fixed and paraffin-embedded tissues on silver-stained nucleolar organizer-region-associated proteins (AgNORs) staining. The treatment of sections at superheated steam temperature (120 degrees C) before silver incubation leads to a significantly better discrimination of single-interphase AgNORs. Counting "black dots" both by eye and by means of a computer-aided image-analyzing system revealed considerably higher AgNOR mean numbers per nucleus in all pretreated cases when compared with the respective untreated controls. However, mean AgNOR numbers increased after autoclave pretreatment in a nonlinear manner (pairwise comparison by means of Spearman's Rank correlation coefficient: rho = 0.5), whereas measurement of the AgNOR area was less influenced by autoclave pretreatment (rho = 0.8). It is concluded that wet autoclave pretreatment of routinely formalin-fixed and paraffin-embedded archival material should be applied before AgNOR staining, particularly when quantitation of AgNORs involves counting procedures.

Adenocarcinoma↗
PubMed1993

Sneddon's syndrome. A long-term follow-up of 21 patients.

BACKGROUND AND DESIGN: Twenty-one patients with histologically proven Sneddon's syndrome were followed up in a retrospective study. We report on their detailed clinical courses and extensive follow-up examinations. RESULTS: Incidence is estimated at four cases per million population per year. Nonspecific prodromal symptoms (headache, dizziness) frequently (80%) precede livedo racemosa for 3.5 and (multi)focal neurological symptoms of fully developed disease for 9 years followed by progressive cognitive impairment (60%) 10 years later. Involvement of fundi, peripheral nerves, heart, and kidneys is frequent (50% to 70%) yet usually asymptomatic. Some symptoms prove irreversible (livedo racemosa, multifocal cerebral lesions on imaging, or creatinine clearance), whereas other symptoms tend to resolve after days to years (many focal neurological symptoms, some electrocardiographic changes, or hypertension). Mortality is calculated at 9.5% within an average observation time of 6.2 years. Laboratory findings, including antiphospholipid antibodies, are normal except for elevated erythrocyte sedimentation rates and complement consumption at times of disease progression and increased cholesterol levels parallel to disease extent. Skin biopsy specimens reveal inflammatory findings ("endothelitis") of small- to medium-sized arteries followed by subendothelial proliferation and fibrosis. Hypertension is the only risk factor significantly associated with a more severe course of the disease; no medication proved effective. CONCLUSIONS: Sneddon's syndrome is an often unrecognized, slowly progressive, systemic disease with evidence of vasculitic origin.

Adult↗
PubMed1993

Presence and possible significance of immunocytochemically demonstrable metallothionein over-expression in primary invasive ductal carcinoma of the breast.

Metallothioneins (MTs) are ubiquitous low-molecular-weight proteins with a high affinity for heavy metal ions such as zinc, copper and cadmium. MT over-expression has been associated with resistance against anticancer drugs. In the present study we investigated 86 cases (45 cases of tumour category pT1 and 41 of category pT2) of routinely fixed and paraffin-embedded primary breast carcinomas immunohistochemically with a monoclonal antibody to an epitope of MT shared by its I and II isoforms. Immunohistochemically demonstrated MT over-expression was found in the invasive components of 7 of 32 pT1 and 17 of 28 pT2 invasive ductal carcinomas, whereas all 26 invasive lobular carcinomas gave weak or negative results. Fourteen of 17 pT2 and 2 of 7 pT1 invasive ductal carcinomas with MT over-expression developed metastases during follow-up with poor prognostic outcome. In contrast only 3 of 11 pT2 and none of the 25 pT1 cases without MT over-expression had a poor clinical course (P < 0.001). It is concluded that MT over-expression is associated with significantly poor prognosis particularly in pT2 invasive ductal breast carcinomas.

Adult↗
PubMed1993

Relationship between quantity of silver stained nucleolar organizer region associated proteins (Ag-NORs) and growth rate suppression of breast cancer cell lines after interferon-gamma and 4-hydroxy-tamoxifen treatment.

The correlation between the silver-stained nucleolar organizer region associated proteins (Ag-NORs) and the growth rate suppression (GRS) of ten established breast cancer cell lines which were treated with 4-hydroxy-tamoxifen (OHT) and interferon-gamma (g-IFN), respectively, was investigated by means of automated image analysis. Previous studies have shown a statistically significant relationship between the Ag-NOR quantity and the population doubling time (PDT) of these cell clones. The results of the present study showed a highly significant correlation between the GRS and the Ag-NOR quantity in estrogen receptor (ER) positive tumour cell lines after OHT treatment (P < 0.001) whereas no strict correlation of these parameters could be demonstrated after g-IFN treatment in both ER positive and negative cell lines. Our results suggest a different behaviour of NOR-proteins in breast cancer cell lines if treated either with g-IFN or OHT, probably reflecting the different mechanism of cell suppression mediated by OHT and g-IFN. It is concluded that quantitative assessment of Ag-NORs is not as suitable for the determination of the GRS as it is for the determination of cell duplication rates obtained on untreated tumour cell lines.

Breast Neoplasms↗
PubMed1993

Immunohistochemically demonstrated metallothionein expression in malignant melanoma.

Metallothioneins are ubiquitous proteins with a high affinity for heavy metal ions, e.g. zinc, copper and cadmium. Experimentally, metallothionein over-expression in cell lines derived from a variety of cancers has been associated with resistance to anticancer drugs and irradiation therapy. Using a monoclonal antibody (E9) to metallothionein we investigated immunoreactive expression in routinely fixed and paraffin-embedded tissue from 63 cases of malignant melanoma and 13 secondary deposits. Whereas a variety of cells in normal skin showed metallothionein expression, all forms of benign naevi studied were uniformly negative. In contrast 13/30 'thin' (< or = 1.5 mm; 0.7 +/- 0.4), 25/29 'thick' malignant melanoma (> 1.5 mm; 5.5 +/- 3.9) and 12/13 metastases were positive. Six patients with thin and 19 with thick melanoma with metallothionein expression died during a mean observation period of 6.4 +/- 1.8 and 3.6 +/- 2.5 years, respectively, their survival distribution function analyses giving statistically significant results for both the vertical tumour thickness (P < 0.0001) and metallothionein expression (P < 0.0001). These immunohistochemical results, based on routinely processed paraffin-embedded tissue, suggest that metallothionein expression in malignant melanoma is significantly associated with progressive disease and might therefore be a useful prognostic indicator.

Adult↗
PubMed1993

Quantitative immunohistochemical evaluation by image analysis of metallothionein in copper-loaded rat kidney.

Kidneys of copper-loaded rats were investigated immunohistochemically with a directly peroxidase-conjugated monoclonal antibody against metallothionein (MT). By means of an image analyzing system the area and the staining intensity of MT immunoreactivity in the proximal convoluted tubule (PCT) cells were determined. In the present study we compared the data obtained by image analysis with analytically determined tissue copper and MT concentrations of rats fed a high-copper diet (1 g/kg) for 16 weeks and sacrificed sequentially during this period. Our results provide evidence that the area of MT immunoreactivity correlates significantly with tissue copper and MT concentrations. Both the copper and MT concentrations in kidney rose to a maximum at 8 weeks and remained constant thereafter. The observed rise in the staining intensity of MT in PCT cells to a maximum at 6 weeks, which subsequently declined, suggests a continuing redistribution of copper and MT in the kidneys even after a maximum of concentration copper and MT is reached in the tissue.

Animals↗
PubMed1993

[Proliferative activity and p53 expression in transitional cell carcinoma of the urinary bladder].

Mutations of the p53 gene are important mechanisms in malignant transformation and are associated with dysregulation of normal cell growth. In the present study the expression of mutated p53-protein and proliferating cell nuclear antigen (PCNA) was investigated in a series of 31 human transitional cell carcinomas (TCC) by immunohistochemistry (IHC). The number of PCNA-positive cells and the pattern of expression was distinct in normal urothelium being confined to the basal cell layer. In dysplastic urothelium and in Carcinoma in situ (CIS) PCNA-immunoreactive nuclei were irregularly distributed throughout all layers. In tumor cell complexes the pattern of PCNA-immunoreactivity was different in papillary and primary infiltrating TCCs. Densitometric quantification of the intensity of the PCNA-reactivity using image analysis revealed an increase from normal to dysplastic urothelium and from dysplastic urothelium to invasive tumors. 21/31 (68%) of the tumors and tumor-associated CIS showed overexpression of p53 varying in percentage, pattern and reaction intensity. The percentage of PCNA-positive cells was higher in tumors overexpressing p53. Double IHC showed colocalization of both molecules in a significant proportion of tumor cells suggesting a link of p53 overexpression and the abnormal proliferative activity. The present results show that p53 over-expression is found in a significant percentage of TCCs and indicate a close association with a defective growth regulation resulting in increased PCNA-levels and enhanced cellular proliferation.

Analysis of Variance↗
PubMed1993

[Pregnancy after kidney transplantation].

11 women gave birth to 13 live-born infants after a mean period of 39.6 months following transplantation, whereby one of these women had two successful pregnancies and one patient had a twin pregnancy. The highly premature twins, born after a complicated pregnancy with impaired renal graft function in the mother, died of respiratory insufficiency on the 13th day. All of these renal allograft recipients had to be delivered by caesarean section, either for nephrological or obstetric reasons. All graft with stable function prior to conception suffered no damage as a result of the pregnancy. In two women with already impaired function, pregnancy led to further deterioration and, eventually, graft loss. Because of the small numbers in this series no conclusions can be drawn with regard to the incidence of malformation of premature delivery. It is concluded that women with normal and stable renal graft function should be allowed to become pregnant. The risk for the graft as well as for the child does not seem to be increased under these circumstances. However, due to the complexity of the situation these patients should be cared for at specialized centres.

Adult↗
PubMed1993

Ultrasonography in the initial evaluation and follow-up of blunt abdominal injury.

BACKGROUND: Ultrasonography has been routinely performed in the assessment of blunt abdominal injury at our department of surgery since 1980. To establish its reliability, a retrospective study was carried out on 818 consecutive patients in the years 1980 to 1990. METHODS: Seven hundred twenty six patients underwent real-time ultrasonographic examination of the abdomen. Indication for ultrasonography included all cases evaluated for blunt abdominal trauma. Ninety two patients before 1985 were excluded. RESULTS: Two hundred seventy (37.2%) patients underwent laparotomy, 252 patients (34.7%) because of ultrasonographic diagnosis. Celiotomy was nontherapeutic in 28 patients; 26 of these patients had positive findings from ultrasonography (false positive, 3.6%). Eighteen patients with negative findings from ultrasonography also underwent laparotomy, which was nontherapeutic in two patients (false negative, 2.2%). Four hundred fifty six patients (62.8%) were managed without operation, relying on initial and follow-up ultrasonography, which was negative in 386 (53.2%) and positive in 70 patients (9.6%). The accuracy of ultrasonography was 94.2%, with 91.9% sensitivity, 96.0% specificity, and 94.9% predictive value. The rate of delayed recognition of documented visceral injury was 5.1%, but no false-negative findings from ultrasonography were noted among these patients. CONCLUSIONS: Ultrasonography has proved to be a thoroughly reliable, cost efficient, and noninvasive modality in primary evaluation and follow-up of blunt abdominal trauma.

Abdominal Injuries↗
PubMed1993

[The effect of various donor factors on primary and long-term function of the transplanted kidney].

Various factors such as cause of brain death, duration of intensive care, single or multiple organ procurement, renal function, heart rate, mean arterial blood pressure, requirement of catecholamines and metabolic derangement were investigated in 86 consecutive organ donors with respect to the possible influence on initial graft function in 86 kidney recipients. Donor conditioning and perioperative recipient management were standardized. Donors of kidneys with initial graft function (group I) showed a significantly higher incidence (80%) of brain death as a consequence of an isolated cerebral incident than donors of kidneys without initial graft function (group II), whereas the incidence of polytrauma (including cerebral) was much higher in donors of group II kidneys (42.9%). The donor requirement of catecholamines was higher in group II donors and the frequency of multiple organ donors was also higher in this group. Five-year graft survival was 80% for group I kidneys but only 62% for group II kidneys. The other factors had no influence on initial graft function. These data demonstrate that multiple injuries and multiple organ procurement have a negative impact on the initial function of the transplanted kidney, possibly due to prolonged ischemic insult.

Acid-Base Equilibrium↗
PubMed1992

Effects of interferons on the expression of the proto-oncogene HER-2 in human ovarian carcinoma cells.

The over-expression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian, endometrial and mammary carcinoma is an important indicator for poor prognosis. We have previously shown in 3 out of 4 ovarian carcinoma cell lines an interferon-gamma (IFN-gamma)-mediated reduction in HER-2 specific protein and RNA levels. The oncogene expression was lowered only in the ovarian carcinoma cell lines but not in 3 IFN-gamma-sensitive human breast cancer cell lines. We extended our observations also to IFN type I, alpha and omega. The expression of the oncogene was measured by both the p185HER-2 ELISA and in selected cases by a living cell radioimmunoassay using the monoclonal antibody (MAb) 4D5 against the extracellular domain. Both IFN types reduced the expression of HER-2 in the ovarian carcinoma cell lines OVCAR-3, HTB-77, 2774 and SKOV-6, and in the SKUT-2 endometrial carcinoma cells. In contrast, SKOV-8 human ovarian carcinoma cells were sensitive for both IFN types regarding proliferation, but only IFN-gamma reduced proto-oncogene expression. In the SKBR-3 human mammary carcinoma cells, neither IFN type had an effect on HER-2 expression. The antibodies 4D5, 7C2, 3E8, and 3H4 which bind to the extracellular domain of p185HER-2 protein specifically inhibited anchorage-independent growth of SKBR-3 and HTB-77 cells. Expression of the oncogene HER-2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which IFNs inhibit cell proliferation.

Antibodies, Monoclonal↗
PubMed1992

Immunohistochemical demonstration of chromogranins A and B in neuroendocrine tumors of the lung.

Fifty neuroendocrine tumors of the lung (16 carcinoids, two atypical carcinoids/well-differentiated neuroendocrine carcinomas [WDNCs], 13 neuroendocrine carcinomas of intermediate cell type [SCNCs], and 19 neuroendocrine carcinomas of small cell type [SCNs]) were immunohistochemically investigated with antibodies against chromogranins A and B. All carcinoids and WDNCs were positive for both chromogranins A and B, whereas in cases of ICNC and SCNC both markers were only expressed in six and five cases, respectively. One ICNC was only positive for chromogranin A. In cases of SCNC five tumors were exclusively positive for chromogranin A and six were positive only for chromogranin B. Chromogranins are therefore excellent markers for the immunohistochemical demonstration of carcinoids and WDNCs. It may be speculated that expression of chromogranins in cases of ICNC and SCNC represents a higher degree of differentiation in these tumors.

Carcinoid Tumor↗
PubMed1992

Deoxyribonucleic acid flow cytometry and semiquantitative histology of spermatogenesis: a comparative study.

OBJECTIVE: To compare deoxyribonucleic acid (DNA) flow cytometry with a semiquantitative histologic method for the assessment of spermatogenesis and to investigate the influence of various preparative techniques on the results of DNA measurements. DESIGN: Testicular tissue from 52 autopsies was examined for spermatogenesis by DNA flow cytometry and by conventional semiquantitative histology. Flow cytometry was performed on single nuclei suspensions from fine needle aspiration biopsies, resuspended imprints, as well as on specimens obtained by mechanical disaggregation of surgical biopsies of the same testis. RESULTS: In all cases, flow cytometry revealed a characteristic distribution pattern of haploid (n), diploid (2n), and tetraploid (4n) cells independent of the preparation technique used. The percentage of haploid cells of the testes showed statistically highly significant correlations (P = 0.0002) with the results of semiquantitative histology. Fine needle aspiration biopsy always contained more haploid cells compared with resuspended imprints and mechanically disaggregated samples. CONCLUSION: Our results confirm the suitability of DNA flow cytometry as a fast and reliable quantitative method for the assessment of spermatogenesis and demonstrate its optimal feasibility in combination with fine needle aspiration biopsy.

Adult↗
PubMed1992

Relationship between quantity of silver stained nucleolar organizer regions associated proteins (Ag-NORs) and population doubling time in ten breast cancer cell lines.

Using a one-step silver staining technique ten human breast cancer cell lines were investigated, determining by means of automated image analysis the mean area of Ag-NORs per nucleus, the total number of Ag-NORs, and the so-called "scattered" and "clustered" Ag-NORs. These parameters were statistically correlated with the population doubling time (PDT) of the various carcinoma cell lines of this series. Our results show that the mean area of Ag-NORs per nucleus (p less than 0.001) is highly significantly correlated to the PDT, whereas all other parameters were less or not significant. It is concluded that the assessment of the area of Ag-NORs by automated image analysis is a simple and reliable method for the determination of cell duplication rates.

Breast Neoplasms↗
PubMed1992

Classic, atypical, and anaplastic meningioma: three histopathological subtypes of clinical relevance.

This study correlates the histopathological classification of meningiomas with clinicopathological features of biological activity. A retrospective evaluation of 1799 surgical specimens of meningiomas from 1582 patients was made. The classic histopathological type, atypical meningiomas defined by increased cellularity and at least five mitotic figures in 10 high-power fields, anaplastic (malignant) meningiomas, and hemangiopericytic or papillary meningiomas were seen in 87.6%, 7.2%, 2.4%, and 2.8% of operations, respectively. The rates of recurrence in surgically treated patients with classic, atypical, anaplastic, and hemangiopericytic or papillary meningiomas were 6.96%, 34.6%, 72.7%, and 68.2%, respectively. The extent of surgery and the tumor size and site were studied in detail in 252 tumors of all histopathological types. Recurrences were rare in classic meningiomas after complete resection, whereas atypical and anaplastic tumors recurred after complete resection much more frequently. Classic meningiomas, hemangiopericytomas, and papillary meningiomas were smaller at surgery than atypical and malignant meningiomas. Atypical and malignant tumors were operated on more often in falcine and lateral convexity regions than were classic meningiomas. To support the authors' subjective categorization by a quantitative parameter related to proliferation, 112 meningiomas comprising all histopathological subtypes were investigated for staining of argyrophilic nucleolar organizer region proteins (Ag-NOR's). The Ag-NOR counts showed significant differences between classic, atypical, and anaplastic tumors but no significant differences between primary and recurrent tumors. Hemangiopericytomas and papillary meningiomas had lower Ag-NOR values than anaplastic meningiomas. A correlation of Ag-NOR numbers with the authors' histopathological scale of malignancy supports the introduction of atypical meningiomas with intermediate biological behavior on the classification scale between classic and anaplastic meningiomas. Overlapping of Ag-NOR numbers among all groups of malignancy may restrict the prognostic value of Ag-NOR counting in the individual case.

Aged↗