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Biomedical subjects

U Kaiser

Publications and source records attributed to U Kaiser.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mantle-cell lymphomas have more widespread disease and a slower response to chemotherapy compared with follicle-center lymphomas: results of a prospective comparative analysis of the German Low-Grade Lymphoma Study Group.

PURPOSE: To compare mantle-cell lymphomas (MCLs) and follicle-center lymphomas (FCLs) for their features of clinical presentation, response to chemotherapy, and prognosis on the basis of a prospective randomized clinical trial. PATIENTS AND METHODS: Patients with MCL and FCL who entered onto the prospective randomized comparison of cyclophosphamide, vincristine, and prednisone (COP) versus prednimustine and mitoxantrone (PmM) followed by a second randomization for interferon (IFN) maintenance versus observation only. RESULTS: One hundred sixty-five of 234 patients had FCL and 45 of 234 patients had MCL. With FCL, both sexes were equally affected (men, 47%); patients with MCL were predominantly men (78%; P < .0004) and had a higher median age (64 v 53 years; P < .0001). Patients with MCL also had more widespread disease, reflected by the proportion of patients with two or greater extranodal manifestations (43% v 21%; P < .005) and nine or greater involved nodal areas (64% v 45%; nonsignificant [NS]). Response to chemotherapy was significantly lower in patients with MCL (complete remission [CR] + partial remission [PR], 69% v 88%; P < .05) and occurred at a slower pace. Patients with MCL also had a shorter event-free interval (median, 8 v 24 months; P < .0001) and overall survival (median, 28 v 77 months; P < .0001). In both subtypes, however, patients with less than two residual lymphoma manifestations in remission experienced a relatively good prognosis with an estimated 5-year survival of greater than 60% for MCL and greater than 75% for FCL. CONCLUSION: MCL and FCL differ substantially in their features of presentation, response to chemotherapy, and long-term prognosis. The extent of residual disease after completion of chemotherapy discriminates patients with different prognosis and may be used for the stratification of postremission strategies.

Adult↗
PubMed1997

The archaeal SoxABCD complex is a proton pump in Sulfolobus acidocaldarius.

The thermoacidophilic archaeon Sulfolobus acidocaldarius expresses a very unusual quinol oxidase, which contains four heme a redox centers and one copper atom. The enzyme was solubilized with dodecyl maltoside and purified to homogeneity by a combination of hydrophobic interaction and anion exchange chromatography. The oxidase complex consists of four polypeptide subunits with apparent molecular masses of 64, 39, 27, and 14 kDa that are encoded by the soxABCD operon (Lübben, M., Kolmerer, B., and Saraste, M. (1992) EMBO J. 11, 805-812). The optical spectra and redox potentials of the SoxABCD complex have been characterized, and the absorption coefficients of the contributing cytochromes a587 and aa3 were determined. The EPR spectra indicate the presence of three low spin and one high spin heme species, the latter associated with the binuclear heme CuB site. Standard midpoint potentials of the cytochrome a587 heme centers were determined as +210 and +270 mV, respectively. The maximum turnover of the complex (1300 s-1 at 65 degrees C) was found to be about three times greater than that of the previously studied isolated cytochrome aa3 subunit alone (Gleissner, M., Elferink, M. G., Driessen, A. J., Konings, W. N., Anemüller, S., and Schäfer, G. (1994) Eur. J. Biochem. 224, 983-990). With N,N,N',N'-tetramethyl-1,4-phenylenediamine as a reductant, the SoxABCD complex reconstituted into liposomes generates a proton motive force. A new method is described by co-reconstitution of SoxABCD with a Sulfolobus Rieske FeS-protein (SoxL), allowing energization by cytochrome c. It is based on the finding that this Rieske protein can equilibrate electrons between cytochrome c and quinones reversibly (Schmidt, C. L., Anemüller, S., Teixeira, M., and Schäfer, G. (1995) FEBS Lett. 359, 239-243). With this system, generating no scalar protons, the stoichiometry of proton translocation could be determined. A net H+/e- ratio >1 was determined, identifying the SoxABCD complex as a proton-pumping quinol oxidase. According to structural analysis, the cytochrome aa3 moiety of the complex does not contain the signature of a H+ pumping channel as identified in Rhodobacter sphaeroides or Paracoccus denitrificans. Therefore, for H+ translocation, a mechanism different from that in typical heme-copper oxidases of the aa3 or bo3 type is discussed.

Bacterial Outer Membrane Proteins↗
PubMed1997

[Value of radiotherapy in disseminated high-grade non-Hodgkin's lymphoma].

BACKGROUND: Radiotherapy is part of the treatment protocols in localized low-grade lymphomas as well as localized high-grade lymphomas adjunct to polychemotherapy. Integration of radiotherapy into the treatment of disseminated high-grade lymphomas is controversial. PATIENTS AND METHOD: The current literature and our own experience with radiotherapy as part of the treatment of disseminated high-grade lymphomas will be discussed. RESULTS: Retrospective analysis of large clinical trials suggest the value of radiotherapy in the treatment of disseminated high-grade lymphomas. Relapse occurs more frequently in non-irradiated regions than in fields of prior radiotherapy. Integration of radiotherapy into treatment protocols seems to be beneficial in patients with bulky disease. A dose/response relationship has been described. The few randomized trials, however, could not clearly demonstrate an advantage of radiotherapy adjuvant to chemotherapy in disseminated lymphomas. A possible advantage can be seen in patients who did not receive more than 4 cycles of polychemotherapy. CONCLUSION: Although the value of radiotherapy adjunct to polychemotherapy in disseminated high-grade lymphomas has not been proven in randomized studies retrospective analysis suggest an advantage. A large randomized study should clarify the role of radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Preferential histiotypic expression of CD44-isoforms in human lung cancer.

The CD44 transmembrane glycoprotein is expressed in most adult tissues and in the majority of neoplasias. Due to alternative splicing, this cell adhesion molecule exists in multiple isoforms some of which have been associated with specific types of tumours as well as with increased tumour metastasis. In this study, we have looked at the level and type of CD44 expression in lung cancer which represents a histologically heterogenous form of cancer composed of small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), the latter subgroup comprising adenocarcinoma (ADC), bronchio-alveolar carcinoma (BAC), large cell carcinoma (LCC), and squamous cell carcinoma (SCC). We analysed 20 lung cancer cell lines and 64 primary tumours by RT-PCR and immunohistochemical detection of the CD44 standard and variant protein isoforms. Our results suggest that (i) CD44 is expressed in all histologically distinct subsets of lung cancer with a tendency SCC > BAC > ADC > LCC > SCLC, (ii) expression of the CD44 isoforms v5, v7, v8, and, most notably that of CD44 exon v6, strongly correlates with tumours of squamous cell and bronchio-alveolar carcinoma origin, tumours which commonly exhibit a comparatively low metastasizing potential, and (iii) the expression of CD44 isoforms is independent from the tumour size and lymph node status at surgery, the proliferative status of the tumour cell population (Ki67 antigen expression) and the histopathological grading (G1 to G3). Only non-differentiated tumours (G4), which were restricted to SCLC and LCC samples revealed markedly reduced CD44 standard and isoform antigen. In conclusion, our data point to a clear histiotype-related pattern of CD44 variant expression preferentially that of CD44v6 in SCC and BAC.

Adenocarcinoma↗
PubMed1997

Chronic eosinophilic leukaemia (CEL): a distinct myeloproliferative disease.

Chronic eosinophilic leukaemia has not yet been clearly defined, mainly due to the fact that it has not been conclusively shown as a monoclonal disease which should be separated from chronic myelogenous leukaemia, acute myelogenous leukaemia with eosinophilia (AML, FAB M4Eo), and the idiopathic hypereosinophilic syndrome. We report a patient with a white blood cell count of 17.6 x 10(9)/l with 74% eosinophils, normal platelet count and haemoglobin. No blasts were seen in the peripheral blood and the percentage of blasts in the bone marrow was < 3%. A diagnosis of chronic eosinophilic leukaemia was made. Chromosome analysis of a bone marrow aspirate disclosed a trisomy 15 together with loss of the Y chromosome. Moreover, FISH analysis on May-Grünwald-Giemsa-stained peripheral blood smears demonstrated trisomy 15 in the eosinophils. 3 months after initial diagnosis the patient went into blast crisis and died. The blast cells exhibited trisomy 15 and loss of the Y chromosome in a complex, aberrant karyotype. In conclusion, the case shows that chronic eosinophilic leukaemia is a monoclonal, myeloproliferative disease with eosinophils as part of the malignant clone. Clinically, chronic eosinophilic leukaemia can be separated into a chronic phase and a blast crisis.

Blast Crisis↗
PubMed1997

[Psychosocial aspects of chronic respiratory tract diseases (COPD): relevance and consequences for pulmonary rehabilitation].

As a part of the Davoser-Reha-Study, the significance of psychosocial aspects on the course of chronic pulmonary disease has been investigated on 414 patients (mean age = 47.1 years) with COPD (mean duration = 16 years) and a high percentage of multimorbidity (75%). Of special interest was the question, what kind of impact coping strategies do have on certain aspects of quality of life, in the sense of outcome criterias of the medical rehabilitation. Also it is not possible for the moment to draw final conclusions, because the knowledge about coping strategies and their adaptability is still very limited, the current study indicates, that some coping strategies are more supportive for adaptation than others. Positive for adaptation are strategies, which can be described as active exposition with the disease (fighting spirit, information seeking and active problem solving). Depressive coping strategies and the tendency to deny the disease seem to have a negative effect. All in all the results verify the strong necessity of taking psychosocial aspects into account for the complete treatment of chronically ill patients with COPD.

Adaptation, Psychological↗
PubMed1996

Steroid-hormone receptors in cell lines and tumor biopsies of human lung cancer.

Female gender is a significant independent favorable prognostic factor in lung cancer. To study the possible role of sex hormones in lung cancer, the expression of sex-steroid receptors and the glucocorticoid receptor was investigated in 29 lung-cancer cell lines stemming from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) by means of immunocytochemistry, ligand-binding assays and RNA expression via polymerase chain reaction. In at least 2 methods of investigation, NSCLC cell lines showed a low expression of estrogen receptor in 6, progesterone receptor in 13 and androgen receptor in 12 out of 17 cases examined; sex-steroid-receptor expression was virtually absent in SCLC cell lines. The glucocorticoid receptor was expressed in all 29 cell lines studied. Additionally, 52 tumor samples from primary lung cancer were investigated for their receptor expression by means of immunohistochemistry. Among patients with primary lung-cancer sex-steroid-receptor expression in tumor biopsies was detected most frequently in female patients (in 69% of 16 cases, vs. 42% of 36 tumors from men) and in patients with adenocarcinoma. Further research will focus on these subgroups. Immunohistology is a feasible method of studying steroid-receptor expression in lung cancer.

Base Sequence↗
PubMed1996

Carboxyl group protonation upon reduction of the Paracoccus denitrificans cytochrome c oxidase: direct evidence by FTIR spectroscopy.

The redox reactions of the cytochrome c oxidase from Paracoccus denitrificans were investigated in a thin-layer cell designed for the combination of electrochemistry under anaerobic conditions with UV/VIS and IR spectroscopy. Quantitative and reversible electrochemical reactions were obtained at a surface-modified electrode for all cofactors as indicated by the optical signals in the 400-700 nm range. Fourier transform infrared (FTIR) difference spectra of reduction and oxidation (reduced-minus-oxidized and oxidized-minus-reduced, respectively) obtained in the 1800-1000 cm(-1) range reveal highly structured band features with major contributions in the amide I (1620-1680 cm(-1)) and amide II (1580-1520 cm(-1)) range which indicate structural rearrangements in the cofactor vicinity. However, the small amplitude of the IR difference signals indicates that these conformational changes are small and affect only individual peptide groups. In the spectral region above 1700 cm(-1), a positive peak in the reduced state (1733 cm(-1)) and negative peak in the oxidized st ate (1745 cm(-1)) are characteristic for the formation and decay of a COOH mode upon reduction. The most obvious interpretation of this difference signal is proton uptake by one Asp or Glu side chain carboxyl group in the reduced state and deprotonation of another Asp or Glu residue. Moreover, both residues could well be coupled as a donor-acceptor pair in the proton transfer chain. An alternative interpretation is in terms of a protonated carboxyl group which shifts to a different environment in the reduced state. The relevance of this first direct observation of protein protonation changes in the cytochrome c oxidase for vectorial proton transfer and the catalytic reaction is discussed.

Electron Transport Complex IV↗
PubMed1996

[Integrative concept on the treatment of highly malignant non-Hodgkin lymphomas].

With CHOP, the standard protocol for the treatment of high-grade non-Hodgkin's lymphomas, about 40% of long term survival has been reported. A recent randomized comparison of CHOP vs. ProMACE-Cyta-BOM vs. m-BACOD vs. MACOP-B showed no advantage of these third generation protocols. The analysis of prognostic factors in several controlled trials and the results of the International Non-Hodgkin's Lymphoma Prognostic Factors Project identified stage, LDH, performance status and number of extranodal sites as the most important pretreatment factors. Already the pretreatment LDH-level (normal vs. enhanced) defines accurately cohorts of patients with low or high risk. Based on these results two cooperative trials were initiated: In trial A we are currently evaluating in a randomised fashion the concept of high dose chemotherapy (BEAM) with autologous stemcell rescue vs. a standard treatment for high risk patients < 60 years. In trial B low risk patients or high risk patients > 60 years are randomised to receive either CHOP or CHOEP at two or three weeks intervals.

Adult↗
PubMed1996

Serum neural cell adhesion molecule differentiates multiple myeloma from paraproteinemias due to other causes.

Serum neural cell adhesion molecule (NCAM) has been described as a prognostic marker in multiple myeloma (MM). Both C-reactive protein (CRP) and beta 2-microglobulin (beta 2M) are established prognostic markers in MM. We tested the diagnostic value of these markers in 212 serum samples of patients with paraproteinemia registered prospectively in a population-based registry. Sixty patients had MM and 152 had other monoclonal gammopathies (hematologic diseases [48], paraneoplastic disease [35], autoimmune disease [15], and monoclonal gammopathy of undetermined significance [56]). CRP and beta 2M had wide and overlapping ranges in all diagnostic categories. However, serum neural cell adhesion molecule (NCAM) was low (< 20 U/mL) in all but 4 of 152 nonmyeloma cases and high (> or = 20 U/mL) in 31 (52%) of the 60 MM cases. Two patients with non-Hodgkin's lymphoma, 1 with chronic lymphatic leukemia, and 1 with autoimmune disease had serum NCAM values between 20 and 30 U/mL. In a discriminant analysis in which serum NCAM, CRP, beta 2M, paraprotein type and concentration, hemoglobin, leukocyte and thrombocyte counts, creatinine, corrected calcium, lactate dehydrogenase, and alkaline phosphatase were included, paraprotein type and concentration and serum NCAM turned out to be the best combination of parameters predicting whether a patient had MM, with 89% of cases being correctly classified. Even without bone marrow and x-ray examinations, serum NCAM, in combination with paraprotein type and concentration, can differentiate between MM and nonmyeloma patients.

Adult↗
PubMed1996

Expression of vitamin D receptor in lung cancer.

The active metabolite of vitamin D 1,25-dihydroxycholecalciferol is a hormone-like agent that regulates cell differentiation and proliferation. Various vitamin D derivatives have been shown to induce differentiation in neoplastic cells. The prerequisite for any hormone action is the presence of its receptor. We studied the expression of vitamin D receptor in human lung cancer cell lines and in primary lung cancer tissue. Employing the polymerase chain reaction, 10 out of 11 cell lines stemming from small-cell lung cancer and 15 out of 15 cell lines stemming from non-small-cell lung cancer demonstrated vitamin D receptor expression. An immunohistochemical analysis, using a specific monoclonal antibody, demonstrated vitamin D receptor protein expression in 31 out of 117 (26%) primary small-cell lung cancer cases tested. Positive cells exhibited a nuclear reaction pattern. Twenty-one out of 37 primary non-small-cell lung cancer cases, particularly adenocarcinomas (9/14) and squamous-cell carcinomas (10/15), exhibited vitamin D receptor. Results indicate that a subset of lung cancer cases may be susceptible to the differentiating effects of vitamin D analogues.

Base Sequence↗
PubMed1996

Soluble CD56 (NCAM): a new differential-diagnostic and prognostic marker in multiple myeloma.

A retrospective study was carried out to determine the diagnostic and prognostic value of the soluble form of the embryonal neural cell adhesion molecule NCAM (CD56) in paraproteinemia. NCAM, beta 2-microglobulin, and interleukin-6 levels were measured in the sera of 170 patients with paraproteinemia. Of these, 125 had multiple myeloma, 20 Waldenström's disease, and 25 monoclonal gammopathy of unknown significance. Serum NCAM proved superior to beta 2-microglobulin and interleukin-6 in distinguishing multiple myeloma from paraproteinemias of various causes, with a high specificity of 95.5% in detecting multiple myeloma, although with a low sensitivity of 40%. In multiple myeloma NCAM is significantly correlated with beta 2-microglobulin, paraproteinemia, and low albumin levels. For the determination of tumor load beta 2-microglobulin levels accord best with the Salmon and Durie classification scheme. When patients are grouped according to their clinical course, the disease development is reflected better by NCAM than by beta 2-microglobulin or interleukin-6. Survival data indicate that all three markers have prognostic potential. Prognostic accuracy with respect to overall survival is best with beta 2-microglobulin.

Biomarkers, Tumor↗
PubMed1996

Expression of bcl-2--protein in small cell lung cancer.

The expression of the proto-oncogene bcl-2, whose main function appears to be an inhibition of apoptosis, was investigated in 164 cases of primary small cell lung cancer by means of immunohistochemistry in a retrospective analysis. One-hundred twenty-five cases (76%) demonstrated expression of bcl-2. There was no difference in serum LDH levels and proliferative activity between the two groups. An analysis revealed a median survival time of 12 months for patients with bcl-2 positive tumors compared to 9.5 months for patients with bcl-2 negative tumors. Although statistical significance is not achieved, there is a trend towards longer survival in patients whose tumors express bcl-2. This tendency is also reflected by a higher rate of complete remission after chemotherapy: 40% in patients with bcl-2+ tumors versus 27% in patients with bcl-2- tumors. In multivariate analysis, tumor stage followed by Karnofsky index were the most valuable predictors for complete remission. LDH and tumor stage were most predictive for 1-year survival. Bcl-2 expression is frequent in SCLC and may reflect a less aggressive mechanism of transformation and a higher susceptibility to cytostatic treatment.

Adult↗
PubMed1996

The neural cell adhesion molecule NCAM in multiple myeloma.

The Neural Cell Adhesion Molecule NCAM is a membrane glycoprotein and belongs to the immunoglobulin superfamily. It is expressed on neural cells as well as on various neuroendocrine tumors and can be detected in sera of patients with small cell lung cancer. Its role is attributed to tumor invasion and formation of metastases. Malignant plasma cells and a subset of plasma cells from patients with monoclonal gammopathy exhibit surface expression of NCAM whereas normal plasma cells do not express NCAM. Expression as measured by flow cytometry using anti-CD56 antibodies does not seem to correlate with clinical course, however leukemic myelomas and myeloma cell lines tend to loose NCAM surface expression. An isoform of NCAM which is rich in polysialic acids and characteristic for embryonal NCAM (eNCAM) has been shown to be elevated in sera of patients with multiple myeloma using a chemiluminescence immunoassay. Patients with progressive myeloma tend to have high serum NCAM levels above the normal range of 20 U/ml. Analysis of 125 myeloma patients suggest that serum NCAM is a valuable parameter for tumor progression rather than tumor mass. Increase in serum NCAM may be associated with loss of adhesive function.

Biomarkers, Tumor↗
PubMed1996

[Using a computer for accessing information in environmental medicine].

Decisions or statements about the health effects of "pollutants" are often based on not exactly known exposure conditions and/or doubtful cause-effect relationships. Even searches in international databases will not always give adequate answers or produce new problems for the specialist in environmental medicine because the information may be contradictory or leave a wide scope for interpretation, perhaps requiring detailed specialized knowledge (e.g. mutagenicity testing, immunotoxicological parameters etc.). In situations like these, inter-disciplinary working is the mandatory condition. Therefore electronic communication systems might be used to resolve problems, because they provide access to well-presented knowledge of competent colleagues. However, the fundamental concept of such mailbox system for environmental medicine requires active participation by all its users who should contribute to its files and not remain passive, i.e. only call for information.

Computer Communication Networks↗
PubMed1995

[Results in stent implants in pelvic arteries: follow-up with color-coded duplex ultrasonography].

Thirty-one patients (26 males, 5 females), treated with percutaneously inserted endoprostheses (stents) in the iliac artery were followed up a mean 1 year (2-60 months) with regard to clinical and non-invasive results, by color duplex ultrasound and (8 cases) angiography. With one exception self-expandable stents (Wallstents) were applied. The indications for stent implantation were PTA-resistant lesions in 78% and treatment of acute complications after PTA in 22%. Primary technical success with an open stent was achieved in all patients. The ankle-arm systolic pressure index (ASPI) increased from mean 0.67 +/- 0.14 to 0.88 +/- 0.17 (p < 0.001). Early stent occlusion occurred in 1 patient (3%), and 9 (24%) further complications (thrombosis, distal embolization, puncture site problems) were treated either by conservative or interventional procedures, and only once by surgical revision. Color duplex ultrasound showed all stents open without stenosis of hemodynamic significance. Angiography demonstrated intimal hyperplasia in 2 patients with stenosis of about 20-25%. At follow-up 61% of the patients were asymptomatic, 32% were improved. Remaining symptoms were due to lesions of the distal arteries and not to obstructions of the stents. Stenting of iliac arteries is a safe and effective treatment for recurrent and/or complex iliac lesions and has become a valuable adjunct in catheter interventions. We conclude that color duplex ultrasound is not only applicable in native arteries but also in stents, and gives reliable results with regard to hemodynamically relevant obstructions.

Aged↗