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Biomedical subjects

G Wulf

Publications and source records attributed to G Wulf.

10 recordsLinked to original sources

Prognostic value of flow cytometrically determined DNA-ploidy, intracellular pH and esterase activity of non-small cell lung carcinomas.

30 surgical specimens of patients with non-small cell lung carcinomas (NSCLC) were investigated. Significant increases of intracellular pH values in epithelial and inflammatory cells, in the percentage of dead epithelial and inflammatory cells and in the cell volume of vital inflammatory cells in cancerous lung tissue were encountered. Furthermore, decreases of the esterase activity of vital epithelial cells and of the percentage of free cell nuclei were observed. The DNA aneuploidy in 36.6% of the tumours was frequently associated with non-squamous cell carcinomas and stage II, III, IV tumours. Patients with DNA aneuploid tumours had a significantly shorter survival rate than those with DNA euploid tumours. Within the different tumour stages a similar tendency was observed which was, however, only significant in stage III tumour patients. Stage III tumours constitute therefore a heterogeneous entity with a worse prognosis for DNA aneuploid tumour patients. The intracellular pH values and esterase activity as well as the cell volume, the percentage of free cell nuclei and dead inflammatory or epithelial cells contained no significant prognostic information.

Adult

[Flow cytometric analysis in non-small-cell bronchial carcinoma and its prognostic significance].

Tumor and lymph node infiltration, and the DNA-ploidy status of a tumor contain prognostic information in addition to the information obtained by histological examination of surgical samples. Specimens from 112 patients with non-small-cell lung carcinoma obtained immediately after surgery were investigated by means of flow cytometry. DNA-aneuploidy was found in 43% of the primary tumors. Independent from tumor stage, patients with DNA-euploid tumors lived significantly longer (p less than 0.01) than with DNA-aneuploid carcinomas. In 29 cases the DNA-ploidy status of the primary tumor (PTU) could be compared with that of the N2 lymph node metastases (LM). 7 samples revealed a change from DNA aneuploidy in the PTU to DNA-euploidy in the LM. Patients with DNA-euploid PTU and DNA-euploid LM lived significantly longer than patients with DNA-aneuploid PTU/DNA-euploid LM, and patients with DNA-aneuploid PTU/DNA-aneuploid LM. In case of lymph node infiltration only the simultaneous measurement of DNA ploidy of PTU and LM offers an accurate prognostic evaluation. Local tumor recurrence exhibited stability of DNA ploidy, showing DNA euploidy in 12 out of 13 PTU and their corresponding recurrent tumor. Thus, the DNA-ploidy status offers additional prognostic informations which is useful for an extended tumor classification.

Carcinoma, Non-Small-Cell Lung

Prognostic value of deoxyribonucleic acid aneuploidy in primary non-small-cell lung carcinomas and their metastases.

The ploidy status of the deoxyribonucleic acid of a malignant lung tumor provides additional information besides histologic grading and tumor staging according to lymph node infiltration and tumor metastasis. Ninety-nine surgical specimens from patients with non-small-cell lung carcinoma were investigated by flow cytometry. Deoxyribonucleic acid aneuploidy was found in 48% of the primary tumors. Patients with deoxyribonucleic acid-euploid tumors showed better survival (p < 0.01) than those with deoxyribonucleic acid-aneuploid carcinomas independent of tumor stage. Deoxyribonucleic acid ploidy status of the primary tumor was compared with that of N2 lymph node metastases in 29 cases. Seven samples showed a change from deoxyribonucleic acid aneuploidy in the primary tumor to deoxyribonucleic acid euploidy in the lymph node metastases. Survival was significantly better for patients with euploid primary tumors and lymph node metastases, followed by patients with deoxyribonucleic acid-aneuploid primary tumors and euploid lymph node metastases. Survival was poorest in patients with deoxyribonucleic acid-aneuploid primary tumors and lymph node metastases. It was observed that only the simultaneous determination of deoxyribonucleic acid ploidy of primary tumors and lymph node metastases permits accurate prognostic evaluation in case of lymph node infiltration.

Actuarial Analysis

Decrease in soluble CD8 antigen levels in splenectomized patients as an index for reduced suppressor/cytotoxic cell activity.

To investigate the effect of splenectomy on lymphocyte subpopulations we monitored changes in serum concentrations of soluble suppressor/cytotoxic (sCD8) and soluble helper/inducer (sCD4) antigen in 11 splenectomized patients. Indications for splenectomy were hereditary spherocytosis in 2, idiopathic thrombocytopenic purpura in 2, gastric carcinoma in 4, Hodgkin's disease in 2 and pancreatitis in 1 patient. Lymphocyte subpopulations were also analyzed by means of conventional immunophenotyping with monoclonal antibodies to CD4 and CD8. We consistently found an early postoperative drop of sCD8 and sCD4 levels within the first week after splenectomy, paralleling changes in the percentages of CD4+ and CD8+ lymphocytes. While alterations of lymphocyte subsets in the peripheral blood were completely reversible and sCD4 levels returned to preoperative values, sCD8 concentrations remained suppressed even 3 months after splenectomy. SCD8 levels at the nadir and those 3 months after splenectomy were significantly lower than preoperative values (P = 0.003, P = 0.149 respectively). Since sCD8 levels reflect suppressor/cytotoxic cell activity, we suggest that suppressor cell activity is reduced in splenectomized patients.

Adult

Activation of lymphocytes induced by recombinant human granulocyte-macrophage colony-stimulating factor in patients with malignant lymphoma.

To investigate effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on lymphoid cells in vivo, we monitored changes in absolute lymphocyte counts, plasma concentrations of soluble interleukin-2 receptor (sIL-2R) and soluble cytotoxic/suppressor (sCD8) antigens, and phenotypic changes of surface membrane antigens of peripheral mononuclear cells from 14 patients with malignant lymphoma treated with rhGM-CSF. Eight of the 14 patients had relapsed or had refractory non-Hodgkin's lymphoma (NHL) and received rhGM-CSF after intensive chemotherapy with novantrone (NO) and high-dose Ara-C (AC) (NOAC) as salvage regimen. Six other patients with NHL or Hodgkin's disease (HD) were in complete remission and treated with rhGM-CSF to enhance peripheral hematopoietic progenitor cell harvest for autografting. An increase in absolute lymphocyte count at the zenith of leukocyte elevation and a drastic increase in concentration of sIL-2R from a median of 565 U/mL to 6,700 U/mL on rhGM-CSF infusion were found in all patients. There was also a moderate increase in sCD8 levels from a median of 277 U/mL to 470 U/mL. Ten patients were available for serial studies of phenotypic changes in surface membrane antigens. A significant increase in CD25+ (IL-2R+) (P = .0020) and CD4+ (P = .0137) lymphocytes was observed in all patients, but no significant change in CD3+, CD8+, TCR delta 1+, or CD19+ cells. Elevations in absolute lymphocyte counts or in concentrations of sIL-2R or sCD8 were not observed in four other patients during recovery from intensive chemotherapy without rhGM-CSF support. Our results provide evidence that administration of rhGM-CSF might activate lymphocytes in vivo. The impact of this activation on the remission rate and duration, as well as survival in patients with NHL, warrants further investigation.

Antigens, CD

Driver workload during differing driving maneuvers.

Motorcycle-automobile accidents occur predominantly when the car driver turns left across the motorcyclist's right-of-way. Efforts to decrease this specific collision configuration, through an increase in motorcycle conspicuity, have concentrated on the physical characteristics of the motorcycle and its rider. The work reported here examines the behavior of car drivers during different driving sequences, in particular during left-turn maneuvers. An experiment is reported that used simultaneous video-taping of the driver and the forward-looking scene. Subjects followed a preset on-road course and were observed for head movements to determine the possibility of structural interference eye-blink frequency, probe-response time, and probe response error, as measures of cognitive or mental workload. In addition, the subjects completed two major subjective workload evaluations as reflections of effort directed to different components of the driving task. Results indicated that there were significant increases in head movements and mental workload during turn sequences compared to straight driving. This result of higher driver workload may be responsible for increasing the potential for detection failure. Such a propensity is also fostered by the higher structural interference that may be expected during turns. Failures to observe during turning sequences have differing outcomes depending on the presence of opposing traffic, as during the left turn, compared with the absence of such opposition, as occurs in the right turn. Also, the less conspicuous the oncoming vehicle in the left turn scenario, the higher the probability of detection failure. At the present time the least conspicuous powered vehicle is the motorcycle.

Accidents, Traffic

Long-term effects of 2'-deoxycoformycin treatment on cytokine production in patients with hairy cell leukemia.

Deoxycoformycin (DCF) has been reported to cause immediate reduction and dysfunction of T lymphocytes, but the long-term effects on immune functions are still not known. As cytokine production is regulated by T helper-inducer lymphocytes and might represent a parameter for functional integrity of immunocompetent cells, we have measured the production of interleukin-2 (IL-2), tumor necrosis factor (TNF), and interferons (IFN) by peripheral mononuclear cells (PMNC) from 10 patients with hairy cell leukemia 11-24 months after end of therapy with DCF. The patients were in continuous remission at the time of study. Despite an absolute reduction in CD3+ and CD4+ lymphocytes. there were no significant differences in IL-2 or TNF release between patients and controls. Except for a significant reduction in IFN-alpha release stimulated by Newcastle disease virus (NDV), IFN productions induced by other mitogens (phytohemagglutinin, PHA; Concanavalin A, ConA; pokeweed mitogen, PWM) and viral antigens were within normal range. There was also a decrease in proliferative responsiveness to PHA, but responses to ConA, PWM, and other viral antigens were normal. In five of the patients, we have monitored closely the changes in IL-2, TNF, and IFN before, during, and after treatment and could demonstrate a rapid normalization of initially decreased IL-2 release in all cases and also of TNF if the initial production was reduced. This study shows that, even though the absolute number of T lymphocytes and helper cells are reduced in the long-term observation after DCF treatment, the capacity to produce IL-2, TNF, and IFN-gamma was within normal range. Parallel to this observation, no opportunistic infections or frequency of infectious complications occurred in these patients.

Adult

Risks of unbalanced progeny at amniocentesis to carriers of chromosome rearrangements: data from United States and Canadian laboratories.

Data on 1,237 prenatal (amniocyte) diagnoses in cases of familial chromosome rearrangements were collated from 79 American and Canadian laboratories. These were added to European data (Daniel et al: Prenatal Diagn 6:315-350, 1986) on 596 reciprocal translocations (rcp) from 71 collaborative laboratories. The total data set was examined for relationships between balanced or unbalanced result and mode of ascertainment, sex of carrier parent, chromosomes involved, and (in cases of reciprocal translocations and pericentric inversions) for potential or actual chromosome imbalance size (% haploid autosome length). Risk rates for unbalanced segregants were markedly dissimilar. These ranged from approximately 50% down to essentially a negligible risk. The risk was approximately 50% for carriers of the following: complex chromosome rearrangements (ccr); insertions (ins); and for 2:2 segregating rcp ascertained by mode 1 (term unbalanced proband) with small imbalance segments. Pooled carriers (either sex) of 2:2 segregating rcp of mode 1 had a risk of 20-25% whereas female Robertsonian (rob) translocation (D;21) carriers and pericentric inversion (pii) carriers of pii with small distal segments had a risk of 10-15%. Pooled 2:2 segregating rcp carriers ascertained by mode 2 (a couple with recurrent miscarriages) and male carriers of rob (D;21) had a risk of 1.5-5%. The risk of unbalanced segregants was 1-2% (in this data) for male and female rob (13;14) carriers and for pooled pericentric inversion carriers. However, for carriers of most "type" (recurrent breakpoints) pii, for all paracentric inversions, and (as expected) for rob not involving 13 or 21, there were no term unbalanced progeny. For 2:2 segregating reciprocal translocations plots were prepared that could be used to determine broad risk groups for carriers of such rcp. In 3:1 segregating rcp there were 3.3 times fewer male than female carriers, whereas there were 1.3 times fewer male carriers in 2:2 segregating rcp. In 2:2 segregating rcp there is little effect on the fertility of male carriers and risks of unbalanced progeny were found to be equal to those for female carriers, whereas in the 3:1 segregating rcp, risks were much less for male as compared to female carriers. This indicates that 3:1 segregating rep are more similar to Robertsonian translocations in their greater effect on the fertility of male carriers.(ABSTRACT TRUNCATED AT 400 WORDS)

Abortion, Habitual

Flow-cytometric determination of high-density-lipoprotein binding sites on human leukocytes.

In this method, leukocytes were isolated from 6 mL of EDTA-blood by density-gradient centrifugation and subsequently incubated with rhodamine isothiocyanate (RITC)-conjugated high-density lipoproteins (HDL). The receptor-bound conjugate particles were determined by fluorescent flow cytometry and compared with 125I-labeled HDL binding data for the same cells. Human granulocytes express the highest number of HDL binding sites (9.4 X 10(4)/cell), followed by monocytes (7.3 X 10(4)/cell) and lymphocytes (4.0 X 10(4)/cell). Compared with conventional analysis of binding of 125I-labeled HDL in tissue-culture dishes, the present determination revealed significantly lower values for nonspecific binding. In competition studies, the conjugate competes for the same binding sites as 125I-labeled HDL. With the use of tetranitromethane-treated HDL3, which fails to compete for the HDL receptor sites while nonspecific binding is not affected, we could clearly distinguish between 37 degrees C surface binding and specific 37 degrees C uptake of RITC-HDL3, confirming that the HDL receptor leads bound HDL particles into an intracellular pathway rather than acting as a "docking" type of receptor. Patients with familial dysbetalipoproteinemia showed a significantly higher number of HDL binding sites in the granulocyte population but normal in lymphocytes and monocytes, indicating increased uptake of cholesterol-containing lipoproteins. In patients with familial hypercholesterolemia, HDL binding was increased in all three cell types, indicating increased cholesterol uptake and increased cholesterol synthesis. The present method allows rapid determination of HDL binding sites in leukocytes from patients with various forms of hyper- and dyslipoproteinemias.

Binding, Competitive