PubMed Health⌕ Search

Biomedical subjects

F Offner

Publications and source records attributed to F Offner.

At least 55 records · Page 3Linked to original sources
PubMed1994

Sequential quantification of AgNOR area and number during silver staining by means of an image analysing system.

Standardized AgNOR staining protocols are required to compare results obtained by means of image analysis systems (IAS) in different laboratories. In order to investigate the staining kinetics of the NOR silver staining, we evaluated automatically the area and number of AgNORs of a human transitional-cell carcinoma cell line (HOK-1) by IAS at one minute intervals over a total staining period of 30 minutes. Results showed a constant increase (standard error of estimate: 0.001; R squared: 0.8) of the AgNOR area reaching a plateau after 10 minutes followed by further area increase. In contrast, in all experiments a pronounced variability in the AgNOR number (standard error of estimate: 0.042; R squared: 0.75) was noted, reflecting the aggregation of silver stained spots. Thus the evaluation of the AgNOR area yielded reliable and easily reproducible results, whereas the assessment of the AgNOR number by means of an automated IAS was associated with a marked variability.

Autoanalysis↗
PubMed1993

Effects of HOE 694--a novel inhibitor of Na+/H+ exchange--on NIH 3T3 fibroblasts expressing the RAS oncogene.

Among the sequelae of ras oncogene expression are intracellular alkalinization and increase of cell volume, both phenomena attributed at least in part to activation of the Na+/H+ exchanger. The present study was performed to elucidate the effects of HOE 694--a novel inhibitor of the Na+/H+ exchanger--on intracellular pH, cell volume, cytoarchitecture and cell proliferation of ras oncogene expressing NIH 3T3 fibroblasts. Following transient exposure of the cells to 20 mmol/l NH3/NH4+, intracellular pH decreases sharply. The following slow realkalinization is completely blocked by 10 mumol/1 HOE 694. Half-maximal inhibition is achieved by 100 nmol/l HOE 694. Cell proliferation is inhibited by HOE 694 with similar potency, whereas the increase in cell volume and cytoskeletal transformation are not prevented, even by 10 mumol/l HOE 694.

3T3 Cells↗
PubMed1992

Granulocyte elastase, tumor necrosis factor-alpha and urokinase levels as prognostic markers in severe infection.

We have examined the prognostic value of the levels in the blood of granulocyte elastase-alpha 1-proteinase inhibitor (E-alpha 1-PI) complex, tumor necrosis factor-alpha (TNF-alpha) and urokinase-type plasminogen activator (u-PA) in 35 patients with severe infection upon admission to an Intensive Care Unit. Fourteen patients died. No differences for E-alpha 1-PI complex were found between survivors and nonsurvivors, but in all patients the levels on admission were eight-fold higher than the reference value. TNF-alpha levels, measured by immunoassay, on admission were four times higher in the nonsurvivors than in the survivors (p = 0.0003) and correlated with the severity of the disease (APACHE II score, r = 0.43, p less than 0.05). TNF-alpha was not detectable by bioassay. Total u-PA antigen (u-PA Ag), plasmin-activatable single-chain u-PA (scu-PA) and inactive, nonactivatable u-PA (u-PA#) were on admission all two-fold higher in the nonsurvivors (p = 0.0006, 0.003 and 0.0003, respectively), while normal in the survivors. In both, survivors and nonsurvivors, the ratio between scu-PA and u-PA Ag was significantly decreased (p less than 0.001, compared to a reference group of healthy volunteers), indicative for enhanced conversion of scu-PA to active two-chain u-PA (tcu-PA) and inactive u-PA# during severe infectious disease. tcu-PA was detected in nine of the 35 patients, while virtually undetectable in controls. scu-PA correlated with the Child-Pugh score on admission (r = 0.42, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Time course of various inflammatory mediators during recurrent endotoxemia.

The time course of thromboxane B2 (TxB2), 6-keto-PGF1 alpha (stable metabolite of prostacyclin), tumor necrosis factor-alpha (TNF alpha), platelet activating factor (PAF), and interleukin-6 (IL-6) formation after three lipopolysaccharide (LPS) infusions was studied in pigs over an 18-hr, period. The Escherichia coli endotoxin W0111:B4 was injected i.v. into 10 of the test group pigs at a dose of 0.5 micrograms/kg over 30 min at 0, 5 and 10 hr of the experiment. Three pigs injected with physiological saline served as controls. At defined time points before and after each LPS administration venous blood was withdrawn (0, 15, 30, 45, 60, 120, 180 min) and plasma levels of TxB2, 6-keto-PGF 1 alpha, PAF, TNF alpha and IL-6 were determined. Pulmonary artery pressure (PAP) and cardiac output (CO) were measured every 15 min. TxB2 and PAF peaked significantly between 30 and 45 min, TNF alpha and 6-keto-PGF 1 alpha between 30 and 60 min, and IL-6 between 120 and 180 min after each LPS injection. The mediators PAF, TNF alpha and TxB2 showed a decreasing three-peak profile whereas 6-keto-PGF1 alpha exhibited an increasing one. IL-6 plasma concentrations increased after each LPS injection. The peak after the third LPS administration, however, was surprisingly low compared to the previous two. The first LPS infusion in our test group led to a significant, sustained rise in mean PAP. After recurrent LPS injections the peak in PAP was not as marked as after the first infusion, indicating the development of a tolerance towards LPS. Initially, CO showed hypodynamic values, whereas the end stage of the experiment was characterized by hyperdynamic CO levels. In conclusion, we believe this porcine model of septic shock to be one of the first large animal models to describe in detail the time-course of various important inflammatory mediators.

6-Ketoprostaglandin F1 alpha↗
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

[Opportunistic malignant lymphomas in SIV infected primates--a model for Epstein-Barr virus associated lymphomas in AIDS].

In a series of 33 cynomolgus monkeys (Macaca fascicularis) experimentally infected with Simian Immunodeficiency virus (SIV), strain smm3, 13 animals developed malignant Non-Hodgkin lymphomas. These lymphomas presented with unusual primary manifestations like in the orbita, testes, and brain. The morphological features and immunophenotyping identified the tumors as high malignant B-cell lymphomas. In all tumors as well as in tumor-derived cell lines a cynomolgus B-lymphotropic herpes virus (CBLV) with structural homogeneity to the Epstein-Barr virus (EBV) could be demonstrated by Southern blotting with EBV-specific probes. The lymphoma cells also expressed CBLV-associated nuclear antigens involved in B-cell transformation crossreacting with EBNA-specific human sera and monoclonal antibodies. Ig-gene rearrangement studies revealed clonal populations, however, no translocations of the c-myc oncogene could be detected. The lymphomas developing with high frequency in SIV-induced immunodeficiency resemble a major subtype of human EBV-associated AIDS lymphomas. This animal model can therefore be used to further elucidate interactions of HIV and EBV in AIDS-related lymphomagenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Fibrinolysis and coagulation in patients with infectious disease and sepsis.

Sepsis is often associated with hemostatic dysfunction. This study aimed to relate changes in fibrinolysis and coagulation parameters to sepsis and sepsis outcome. Urokinase-type plasminogen activator (u-PA) antigen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) type 1 antigen, PAI activity, antithrombin (AT) III activity, and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non-sepsis patients with severe infectious disease. The u-PA level was markedly increased in plasma of sepsis patients as compared to non-sepsis patients (11.5 +/- 9.4 versus 1.6 +/- 1.5 ng/ml, p less than 0.0001). PAI-1 antigen and t-PA activity showed a significant increase in sepsis patients (320 +/- 390 ng/ml versus 120 +/- 200 ng/ml, and 3.0 +/- 3.6 IU/ml versus 1.0 +/- 0.7 IU/ml, respectively, p less than 0.01). AT III was decreased in sepsis patients (58 +/- 28% in sepsis versus 79 +/- 26% in severe infectious disease, p less than 0.01) as was protein C (30 +/- 18% versus 58 +/- 27%, p less than 0.001). No significant difference was found for t-PA antigen nor for PAI activity. Nonsurvivors of sepsis were distinguished mainly by a high u-PA antigen level and increased t-PA activity. It is concluded that plasma u-PA antigen showed the strongest significant difference, among the parameters evaluated, between sepsis and severe infection. u-PA antigen may be of prognostic value in patients admitted to the medical intensive care unit for severe infectious disease.

Adult↗
PubMed1991

Anatomic nature and surgical significance of anal sinus and anal intramuscular glands.

The nature of anal sinus and anal intramuscular glands is well known, but their origin is still discussed. In the past years a surprising new theory about the invagination of the proctodeum into the hindgut was put forward. Evidence supporting this theory would be the existence of an "anorectal band" and "epithelial debris" in the subanoderm formed during total or partial obliteration of the anal sinuses. To characterize these histological structures, the authors examined 62 autopsy specimens with conventional and special immunohistologic staining methods. In none of the examined specimens could the structures mentioned above be detected. Nearly 90 percent of our specimens contained the well known anal sinuses. In fetuses, neonatal deaths, and children, more than one-half of the anal sinuses were accompanied by anal intramuscular glands penetrating the internal anal sphincter, whereas in adult specimens the anal intramuscular glands were rare. Eight postoperative, idiopathic chronic anal fissures and three postoperative anal fistulas examined with the same staining procedures showed epithelial cells at the base of the fissures or fistulas in two cases (25 percent) and three cases (100 percent), respectively. The results reinforce the theory that anal sinuses and anal intramuscular glands are separate anatomic entities and indicate a new theory of anal development. For idiopathic, chronic anal diseases anal sinuses have little surgical significance. Anal intramuscular glands should be the anatomic correlate of anal fistulas.

Adolescent↗
PubMed1991

Thymoma: a clinicopathological comparative study of 25 cases.

We reviewed 25 patients with thymoma for clinical symptoms at presentation, X-ray findings and outcome. The tumours of all patients were classified using 3 different pathologic classification systems and each system was evaluated for its predictive power with respect to survival. The recent classification system by Müller-Hermelink allowed to distinguish thymomas with associated systemic syndromes from those without. However, no good prediction with respect to outcome could be made by any of the 3 systems.

Actuarial Analysis↗
PubMed1991

Extra translocation +der(1q9p) is a prognostic indicator in myeloproliferative disorders.

An identical extra derivative chromosome resulting from a translocation between the long arm of chromosome 1 and the short arm of chromosome 9, +der(1q9p), has been observed in three patients with a myeloproliferative disorder. Two patients had polycythemia vera in transformation (erythroleukemia in one patient and refractory anemia in the second), whereas the third patient had myelofibrosis which later evolved into acute myelomonocytic leukemia. The two patients who developed overt leukemia did not receive any previous cytotoxic treatment. Non-isotopic in situ hybridization was performed in two patients, allowing for the localization of the breakpoints in 1q12 and 9q12. A similar rearrangement has been previously described in patients with polycythemia vera, either at diagnosis or in advanced stages of the disease. These data suggest that this chromosome abnormality may be consistently associated with myeloproliferative disorders showing a high propensity to transformation, which is not treatment related, and the finding of the +der(1q9p) may represent a poor prognostic sign when observed in the chronic phase.

Chromosome Aberrations↗
PubMed1990

Sclerosis of the internal anal sphincter--a process of aging.

Functional and organic alterations such as sclerosis of the internal anal sphincter muscle are often discussed as a cause of proctologic diseases. Systematic histopathologic examinations of this muscle are rare, although the internal anal sphincter is of primary significance for the continence of the anal canal and its functional efficiency. The authors believe that the degree of formation of connective tissue in this unstriated muscle depends on the age of the examined specimen. The authors can demonstrate that sclerosis is a physiologic process of aging.

Aging↗
PubMed1990

Wegener's granulomatosis: a review of 5 cases.

Wegener granulomatosis is a systemic disease with a wide spectrum of clinical manifestations. This is illustrated by 5 case reports. The diagnostic value of clinical, radiological, histological and serological signs are discussed and compared with the literature. Diagnosis has been facilitated by the introduction of serological tests: (anti-cytoplasmic antibody (ACPA) titer). High remission rates can be obtained with combined cyclophosphamide and prednisolone treatment. In case of a rapidly progressive glomerulonephritis, plasmapheresis presents a possible therapeutic advantage.

Adolescent↗
PubMed1990

Serum tumor necrosis factor levels in patients with infectious disease and septic shock.

The role of tumor necrosis factor (TNF-alpha) in the pathogenesis of septic shock has been assessed by daily measurements of serum TNF-alpha levels in 60 patients admitted to the medical intensive care unit. All patients in the study had infectious disease and were at risk for the development of sepsis and septic shock. Sepsis was diagnosed in 34 patients, 24 of whom died (six within the first 24 hours). The 26 patients who did not evolve toward sepsis served as a control group. The clinical condition of all patients was monitored by daily APACHE II scoring. Blood was drawn once a day and additional samples were taken in patients whose clinical condition underwent sudden deterioration. TNF-alpha levels were measured with a commercially available immunoradiometric assay. At time of patient admission, TNF-alpha levels were higher in the group with sepsis than in the control group (median 79 iqr 329 vs median 0.5 iqr 5; p less than 0.001). In the group with sepsis, extremely high TNF-alpha levels were found in patients who died within 24 hours. These patients had TNF-alpha levels of 917 iqr 755 pg/ml, whereas the patients who died more than 24 hours after admission had TNF-alpha levels of 58 iqr 59 pg/ml. Survivors had lower TNF-alpha levels (26 iqr 347 pg/ml). APACHE II scores correlated with TNF-alpha levels in the total sepsis group (Spearman rank correlation coefficient 0.477; p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗
PubMed1989

Immunodeficiency in old age.

Aging is a multi-facetted process, but the deterioration of the immune function seems to play a central role in this context. Paradoxically, immune reactivity against exogenous antigens declines during aging while autoimmune reactivity increases. One of the aims of our investigations on the function of the senescent immune system was to define immune parameters of 'normal' aging, i.e. those not dependent on underlying diseases. Specifically, our interest was focused on the possible role of an altered lipid metabolism of cells of the immune system during aging. The known decrease of plasma membrane fluidity of lymphoid cells and monocytes in higher age may be one of the factors responsible for the nonoptimal functioning of the immune system. This property, in turn, seems to be based on an altered lipid metabolism. Specifically, we have evidence that the finely tuned balance between the transport of cholesterol to and from lymphoid cells via the environment and the intracellular cholesterol biosynthesis seems to be disturbed with increasing age. This conclusion is drawn from experiments where low-density lipoprotein (LDL) and high-density lipoprotein (HDL) receptor activity is assessed using fluorescently labeled lipoproteins in fluorescence-activated cell sorter (FACS) analyses. LDL receptor uptake is unexpectedly increased in the elderly, but LDL receptor regulation, and serum LDL composition itself seem to be normal. Preliminary data point out the possibility that the efflux of cholesterol via HDL may be insufficient. Attempts to modulate plasma membrane fluidity by means of the phospholipid mixture 'active lipid 721' (AL 721) showed that this drug, in contrast to literature reports, is not a 'membrane fluidizer' but rather exerts this effect as a nutrient for lymphocytes and monocytes.

Aging↗
PubMed1988

Lipid requirements of human T lymphocytes stimulated with mitogen in serum-free medium. Membrane "fluidity" changes are an artefact of lipid (AL721) uptake by monocytes.

A correlation has been sought between the effects of lipids on membrane fluidity and mitogen responsiveness of human peripheral blood lymphocytes (PBL). Cholesterol and the reputedly potent membrane fluidizing agent AL721 (1) were used for these studies. However, the large AL721 induced increase in membrane "fluidity", assessed by steady state polarization of the probe 1,6-diphenyl-1,3,5-hexatriene (DPH), was found to be an artefact arising from lipid uptake by monocytes. Mitogen responses were enhanced by AL721 but unaffected by cholesterol. It is concluded that AL721 does not exert its effect through enhanced triggering of cells by altered membrane fluidity but rather that lymphocytes require an exogenous source of phospholipids/triglycerides for optimal growth in vitro, although they can synthesize sufficient cholesterol to meet their own needs.

Adult↗