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Biomedical subjects

H Neef

Publications and source records attributed to H Neef.

At least 19 recordsLinked to original sources
PubMed2002

Microscopic (R1) and macroscopic (R2) residual disease in patients with resected non-small cell lung cancer.

OBJECTIVES: This retrospective study evaluates the probability of survival in patients who had undergone resection for non-small cell lung cancer (NSCLC) and in whom residual disease at the resection margins was found. METHODS: During a period of 6 years, 596 patients with NSCLC were operated upon with curative intention. Residual disease at the resection margin was divided into microscopic (R1) and macroscopic (R2). RESULTS: Twenty-six patients (4.4%) showed R1 and 12 (2%) R2 residual disease. An extrabronchial (thoracic wall, vessels) R1 situation was found in five patients and a bronchial R1 infiltration in 21 cases. The bronchial resection margin was subject to peribronchial infiltration in most cases (16/21). A total of 17/21 (65%) patients with bronchial infiltration had N2 disease. Thirty day lethality was 3.8% in the R1 group. Fifteen patients had postoperative irradiation. The 5-year survival rate for patients with R1 resection was 14%. The differences in survival between patients with extrabronchial vs. bronchial infiltration and N0/N1 vs. N2 were significant using univariate analysis. Adjuvant radiation did not result (especially in N2 disease) in a survival benefit. Among 12 patients with macroscopic residual disease (R2), 3/12 (25%) died within the first 30 days after the operation, and none of the R2 patients survived the first year after the operation. CONCLUSIONS: Patients with an R1 situation have a survival rate of 14% comparable to curative resected patients (RO) in stage III. Adjuvant radiation had no clear effect on survival. Patients with macroscopic tumor (R2) should receive palliative treatment after the operation depending on their condition.

Adenocarcinoma↗
PubMed2002

Iatrogenic ruptures of the tracheobronchial tree.

OBJECTIVE: Iatrogenic tracheobronchial ruptures are seldom but severe complications after intubation or bronchoscopy. Therefore, we evaluated the reasons, the subsequent therapy and the outcome of patients with tracheal rupture, who were admitted to our hospital. METHODS: In a retrospective study we examined 19 patients (15 women, four men; 43-87 years) treated for acute tracheobronchial lesions. Eleven (58%) patients had a tracheobronchial rupture by single-lumen tube, four (21%) by double-lumen tube and two patients (10%) by tracheal cannula. A total of 47% of whom were carried out under emergency conditions. Two patients had a rupture due to a stiff bronchoscopy. Mean symptoms were mediastinal and subcutaneous emphysema. Two emergency collar incisions had been done. RESULTS: The localization of ruptures was in all cases in the paries membranaceus, length: 1-7 cm (mean: 4.8 cm). The interval between the onset of symptoms and the diagnose differed widely (up to 72 h), nine (47%) diagnoses were made during intubation/bronchoscopy. One patient, with a small tear (1 cm) was treated conservatively with fibrin-glue. The other 18 patients had surgical repair through a thoracotomy. The postoperative mortality was determined with 42%, which was not dependent on the rupture but basically by the underlying diseases requiring intubation. CONCLUSIONS: Iatrogenic tracheal rupture is a dangerous complication with potentially high postoperative mortality, mostly influenced by the underlying disease. Early surgical repair must be the preferred treatment.

Adult↗
PubMed2001

Examination of donor substrate conversion in yeast transketolase.

The cleavage of the donor substrate d-xylulose 5-phosphate by wild-type and H263A mutant yeast transketolase was studied using enzyme kinetics and circular dichroism spectroscopy. The enzymes are able to catalyze the cleavage of donor substrates, the first half-reaction, even in the absence of any acceptor substrate yielding d-glyceraldehyde 3-phosphate as measured in the coupled optical test according to Kochetov (Kochetov, G. A. (1982) Methods Enzymol. 90, 209-223) and compared with the H263A variant. Overall, the H263A mutant enzyme is less active than the wild-type. However, an increase in the rate constant of the release of the enzyme-bound glycolyl moiety was observed and related to a stabilization of the "active glycolaldehyde" (alpha-carbanion) by histidine 263. Chemically synthesized dl-(alpha,beta-dihydroxyethyl)thiamin diphosphate is bound to wild-type transketolase with an apparent K(D) of 4.3 +/- 0.8 microm (racemate) calculated from titration experiments using circular dichroism spectroscopy. Both enantiomers are cleaved by the enzyme at different rates. In contrast to the enzyme-generated alpha-carbanion of (alpha,beta-dihydroxyethyl)thiamin diphosphate formed by decarboxylation of hydroxylactylthiamin diphosphate after incubation of transketolase with beta-hydroxypyruvate, the synthesized dl-(alpha,beta-dihydroxyethyl)thiamin diphosphate did not work as donor substrate when erythrose 4-phosphate is used as acceptor substrate in the coupled enzymatic test according to Sprenger (Sprenger, G. A., Schörken, U., Sprenger, G., and Sahm, H. (1995) Eur. J. Biochem. 230, 525-532).

Amino Acid Substitution↗
PubMed2001

Flow cytometric analysis of DNA content and proliferation and immunohistochemical staining of Ki-67 in non-small cell lung cancer.

BACKGROUND: The aim of our study was to examine the significance of tumour DNA-content and proliferation in lung cancer. METHODS: The DNA content and S-phase fraction (SPF) was determined by flow cytometry in 125 resected tumours of patients with non-small cell lung cancer. In 40 cases we compared the SPF with immunohistochemical staining of the Ki-67 protein using MIB-1 antibody. RESULTS: DNA aneuploidy was detected in 84.8% (106/125). Cell cycle analysis for the determination of proliferation activity was only possible in 69 (55.2%) cases. An SPF of 0-8% as a sign of low proliferation was found in 27 specimens. In advanced tumours at stage III and IV the proportion of tumours with SPF 9-16% was significantly (p<0.05) increased as compared to tumours at stage I and II. There was a significant correlation (p=0.012, ascent: 0.045) between SPF and MIB-1. Patients with aneuploid tumours had a relative risk of 1.4 to die earlier than patients with diploid tumours. Patients with SPF of 9-16% in the tumour tended to decreased survival (5-year survival rate: 29%) in correlation to patients with a percentage of SPF 0-8% (5-year survival rate: 38%, p=0.5). These differences were significant (p=0.048) in patients with adenocarcinomas only. In the multivariate COX-regression model age (p=0.03) and stage (p=0.0001) were significant prognostic factors, ploidy state (p=0.33) was of no prognostic significance. CONCLUSIONS: Flow cytometry seems to be a useful method for understanding the clinical behaviour of lung cancer. Especially the SPF in adenocarcinomas may be used as a prognostic indicator.

Analysis of Variance↗
PubMed1999

[Functional outcome and quality of life at least 6 months after pneumonectomy--effect of operation, adjuvant therapy, tumor stage, sex, type of pneumonia and recurrence].

This study reports on the results of a checkup carried out on 38 patients subjected to an extended cancer aftercare examination at least 6 months after pneumectomy because of bronchial carcinoma, 12 of these patients receiving adjuvant chemotherapy and/or radiotherapy. Lung function data determined by body plethysmography were measured, as well as the quality of life, using the Karnofsky and Spitzer indices as well as QLQ-C30 of the EORTC. In addition, anamnestic data and postoperative ECG and blood gas analysis results were recorded. The most important findings concern restricted lung function due to pneumectomy, an IVC decrease by 33.3%, a drop in FEV1 by 27.3% and a reduction of the total lung capacity (TLC) by 14%. Moreover, a distinctly increased right heart load was seen in 23.4% of all patients. The quality of life tests revealed a slightly reduced quality of life in the external assessment indices according to Karnofsky (86 +/- 11%) and Spitzer (8.6 +/- 1.2). Self-assessment by QLQ-C30 of the EORTC, however, evidenced a clear reduction of the global quality of life (54.2 +/- 15.6) and role function, a moderate decrease of physical, emotional, cognitive and social functioning as well as a greatly increased incidence of the symptoms fatigue, dyspnea, sleep disturbances and pain after surgery. Adjuvant therapy applied in 12 patients had no significant influence, neither on lung function parameters nor on the quality of life. A more advanced tumour stage or a relapse, however, will adversely affect the quality of life.

Adult↗
PubMed1998

Activation of thiamin diphosphate in enzymes.

Activation of the coenzyme ThDP was studied by measuring the kinetics of deprotonation at the C2 carbon of thiamin diphosphate in the enzymes pyruvate decarboxylase, transketolase, pyruvate dehydrogenase complex, pyruvate oxidase, in site-specific mutant enzymes and in enzyme complexes containing coenzyme analogues by proton/deuterium exchange detected by 1H-NMR spectroscopy. The respective deprotonation rate constant is above the catalytic constant in all enzymes investigated. The fast deprotonation requires the presence of an activator in pyruvate decarboxylase from yeast, showing the allosteric regulation of this enzyme to be accomplished by an increase in the C2-H dissociation rate of the enzyme-bound thiamin diphosphate. The data of the thiamin diphosphate analogues and of the mutant enzymes show the N1' atom and the 4'-NH2 group to be essential for the activation of the coenzyme and a conserved glutamate involved in the proton abstraction mechanism of the enzyme-bound thiamin diphosphate.

Allosteric Regulation↗
PubMed1998

Theoretical studies on the electronic and energetic properties of the aminopyrimidine part of thiamin diphosphate.

Ab initio calculations on the HF-SCF 6-31g* level were performed on tautomers as well as protonated and deprotonated species of thiamin. Aspects of the proton relay function of the 4'-aminopyrimidine ring in the thiamin catalysis were studied on model systems. The acidity of the 4'-amino group increases in the N1' and N3' protonated thiamin systems. Starting from the 4'N deprotonated thiamin, the calculated reaction coordinate of the ylide formation suggests the cocatalytic function of the 4'-amino/imino group. Some structural, energetic, and electronic properties of the model systems are discussed with respect to key steps in the catalytic mechanism.

Gases↗
PubMed1998

[Primary liposarcomas of the mediastinum].

Primary liposarcomas of the mediastinum are rare neoplasms comprising less than 1% of mediastinal tumors. While in early stages often asymptomatic they may grow to an enormous size and then exhibit various clinical symptoms mimicking lung or heart disease by compression of adjacent intrathoracic organs. Intention of surgical treatment is to relieve the symptoms and to establish the histological diagnosis. Surgery alone may be curative in some cases. The role of additional radio- and chemotherapy remains questionable. We report two cases of primary mediastinal liposarcomas that were treated surgically in our institution.

Aged↗
PubMed1998

[Prognostic factors and subsequent indications for surgery in pulmonary metastasis of renal cell carcinoma].

Between 1975-1996, 39 patients underwent resection of pulmonary metastases from renal cell carcinoma. Multivariate analysis (COX model) for survival of preoperative risk factors showed that time of diagnosis (syn-/metachronous) of the metastases (p = 0.05) and the number of metastases (p = 0.01) were of prognostic significance. It is concluded that metastasectomy in patients with not more than six metachronous metastases after renal cell carcinoma has significant benefit and in cases of synchronous metastases or more than 6 pulmonary metastases indication for resection should be restricted.

Adult↗
PubMed1998

Alloplastic sternal replacement in malignant sternal tumors. Case report and review of the literature.

Although not seldom as a palliative procedure, the preferred treatment of locally recurrent breast cancer or chest wall involvement by metastases is full-thickness chest wall resection. For closure and coverage of the defect various techniques are described. Autoplastic reconstruction is indicated for smaller defects, while larger defects usually require alloplastic materials, especially in case of chest instability after resection. We report the case of a 55-year-old female who developed a locally recurrent breast cancer with infiltration of the sternum 4 years after left sided ablation. En bloc resection of the chest wall including the complete sternum was followed by replacement with a computer-aided custom made polyethylene sternal prosthesis. With this procedure we stabilized the chest wall with protection of the underlying organs, avoided prolonged postoperative ventilation and achieved a satisfying cosmetic result.

Biocompatible Materials↗
PubMed1997

Molecular mechanism of regulation of the pyruvate dehydrogenase complex from E. coli.

The pyruvate dehydrogenase multienzyme complex from E. coli shows a sigmoidal dependency of the reaction rate on the substrate concentration when product formation is followed in the presence of physiological concentrations of the cofactor thiamin diphosphate. To elucidate the molecular mechanism of this regulation, the influence of the substrate pyruvate on the coenzyme-protein interaction has been investigated using several coenzyme analogues. The observed binding constants of all coenzymatically active analogues are increased in the presence of the substrate pyruvate, whereas those of all coenzymatically inactive analogues are not altered in the presence of pyruvate. This points to an increased binding affinity of a reaction-intermediate-coenzyme complex to the protein. Since cofactor binding and dissociation at physiological concentrations of thiamin diphosphate are slow compared to the catalytic reaction, a slow transition to the active state of the enzyme occurs. After lowering the pyruvate concentration, the opposite effect, a dissociation of the thiamin diphosphate from the enzyme is observed. This slow substrate dependent enhancement of cofactor binding enables efficient regulation of the pyruvate dehydrogenase complex by its substrate pyruvate.

Coenzymes↗
PubMed1997

How thiamine diphosphate is activated in enzymes.

The controversial question of how thiamine diphosphate, the biologically active form of vitamin B1, is activated in different enzymes has been addressed. Activation of the coenzyme was studied by measuring thermodynamics and kinetics of deprotonation at the carbon in the 2-position (C2) of thiamine diphosphate in the enzymes pyruvate decarboxylase and transketolase by use of nuclear magnetic resonance spectroscopy, proton/deuterium exchange, coenzyme analogs, and site-specific mutant enzymes. Interaction of a glutamate with the nitrogen in the 1'-position in the pyrimidine ring activated the 4'-amino group to act as an efficient proton acceptor for the C2 proton. The protein component accelerated the deprotonation of the C2 atom by several orders of magnitude, beyond the rate of the overall enzyme reaction. Therefore, the earlier proposed concerted mechanism or stabilization of a C2 carbanion can be excluded.

Allosteric Regulation↗
PubMed1997

Concentrations of lysosomal cysteine proteases are decreased in renal cell carcinoma compared with normal kidney.

Renal cell carcinoma contains significantly lower concentrations of the lysosomal cysteine proteases, cathepsins B, C, H, L and S, than does normal kidney, as shown by several methods, such as activity determination, enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry. The same low levels of enzyme activity and concentration have been determined in renal cell carcinoma metastases in the lung. Our results on the decreased concentration of cysteine peptidases at the protein level would seem to conflict with earlier results on an increased concentration of the cathepsin L mRNA in renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed1997

Phenotypic analysis of T lymphocytes isolated from non-small-cell lung cancer.

BACKGROUND: The study of the nature of tumor-infiltrating lymphocytes (TIL) may provide insight into the complex issue of tumor-host interactions. METHODS: Cytofluorometric analysis was performed to characterize the phenotypic profiles of TIL from non-small-cell lung cancers (NSCLC) and pulmonal metastases of different primary locations. An extensive panel of antibodies was used specific to different activation-associated molecules on T cells. In 10 patients, findings on the T cell phenotype of TIL were compared with the findings in peripheral blood lymphocytes (PBL) from the same patients. Furthermore, we investigated whether the measurement of the TIL phenotype might serve as a prognostic parameter correlating with survival of patients with NSCLC. RESULTS: In contrast to PBL, T cells infiltrating lung tumors expressed significantly higher amounts of various activation antigens. However, the immunophenotype of TIL hardly differed among different histological subtypes and pulmonal metastases. Addressing the prognostic value of the lymphocytic composition of TIL, we found no significant difference in the survival of NSCLC with high or low percentages of T and natural killer cells, whereas high percentages of B cells were associated with increased survival (p = 0.05). Patients with high percentages of CD13+ tumor-infiltrating T cells had significantly poorer prognosis according to Cox's multivariate analysis. CONCLUSION: Our results indicate that different tumor histologies within the lung are characterized by a 'similar' T cell phenotype, at least with respect to the surface molecules studied by us. The measurement of the expression of activation-associated markers on T cells may have prognostic value in the pathological evaluation of NSCLC.

Adult↗
PubMed1997

[Quality of life after pneumonectomy for bronchial carcinoma].

UNLABELLED: Quality of life measurements gained increasing importance in the last years. After lung tissue reducing interventions for bronchogenic carcinoma quality of life measurements play an important role, since quality of life can be decisively influenced by post-operative reduced lung function. On the basis of postoperative physical symptoms and lung function the restriction of quality of life after pneumonectomy should be analyzed with respect to intervention and adjuvant therapy, 36 patients with an average age of 61 years were followed up by ambulatory oncological care for 40 months (median) after operation and lung function as well as quality of life were measured by self assessment index QLQ- C 30 of EORTC. RESULTS: Beside physical symptoms (increasing of dyspnea by 61.1% and pain by 30.6% after pneumonectomy as compared to preoperative values) the significant reduced lung function (IVC by 33.5%, FEV 1 by 27.1%) and the QL-measurement showed the greatest restrictions, latter in "Physical functioning" by 27.2%, in "Role functioning" by 45.8% and in "Global health status/ Quality of life" by 45.6%. The symptoms "Fatigue" (Score 39.8), "Dyspnea" (50,9), "Pain" (29.6) and "Sleep disturbance" (35.2; max. score 100 = high frequency) were most often found. Further adjuvant therapy (at least 6 months after completion) in 11 patients and the type of pneumonectomy (right-side: n = 11, left-side: n = 25) did not result in additional significant reduction of lung function and of single quality of life dimensions, except that "Dyspnea" in patients with right-sided pneumonectomy (66.7) was significantly more frequent than in patients with left-sided pneumonectomy (44.0). CONCLUSIONS: In this study the restricted quality of life after pneumonectomy was mainly caused by reduction of cardiopulmonary function (reduced lung function by loss of parenchyma). Adjuvant therapy reduced neither lung function nor quality of life. Compared to quality of life measurements after lung resection [17] quality of life after pneumonectomy didn't worse.

Activities of Daily Living↗
PubMed1997

[Tracheobronchial injuries in blunt thoracic trauma].

UNLABELLED: Tracheobronchial lesions after blunt chest injury are seldom (0,5-0,7%). Diagnostic and therapeutic strategies in 16 own cases and a review of the literature are presented. Own experiences: Locations of the lesions were main bronchus (10), bronchus intermedius (2), and trachea (4). Rupture was total in five cases, and partial in seven. In four patients the mucosa only was ruptured. Initial symptoms: Subcutaneous emphysema (13), pneumothorax (9), respiratory insufficiency (5), lung lesion (5), but tracheal bleeding in five cases only. Diagnosis mainly by bronchoscopy (8 early, 4 late), but in 4 cases after thoracotomy. TREATMENT: In cases of total rupture, there were three anastomoses of the bronchus and one of the trachea, and one pneumonectomy. In all partial ruptures, there was suturing of the lesion. Mucosa lesions were treated conservatively. RESULTS: 1 empyema, 2 ex. leth. (bilateral pneumonia 7.d., multiple organ failure 20. d). FOLLOW UP: 9 patients free of symptoms, 5 patients with respiratory problems. The symptoms "mediastinal emphysema and continuous air leakage through the chest tube or persistent atelectasis of the lung" are indications for urgent bronchoscopy and early surgery. Long-term results are good in 70%-90% of the cases. Not diagnosed lesions can result in tracheobronchial stenosis and infections of the lung later on, to be treated by lung resection only. Total bronchial ruptures can result in strictures and non-infected atelectasis, resection of the stricture and reinflation of the lung being successful in 60%-70% of these late diagnosed cases.

Adult↗
PubMed1995

The presence of a hydroxyl group at the C-1 atom of the transketolase substrate molecule is necessary for the enzyme to perform the transferase reaction.

Transketolase catalyzes the transfer of an aldehyde residue from keto sugars to aldo sugars. The intermediate product is dihydroxyethylthiamine pyrophosphate (DHETPP). In the absence of an acceptor substrate, the reaction is stopped at this stage and DHETPP does not undergo subsequent transformations. Pyruvate decarboxylase catalyses pyruvate decarboxylation to yield free aldehyde. The intermediate product is hydroxyethylthiamine pyrophosphate (HETPP). It differs from DHETPP only in that it has no hydroxyl at the C-2 atom of the aldehyde residue. We have shown that transketolase can bind HETPP and split the aldehyde residue from it. This fact suggests that the path of the reaction is determined by the absence (in HETPP) or presence (in DHETPP) of a hydroxyl group. In the former case the reaction will yield free aldehyde, in the latter the aldehyde residue will be transferred onto an acceptor substrate.

Apoenzymes↗