Search PubMed⌕ Search

Biomedical subjects

W Meier

Publications and source records attributed to W Meier.

At least 73 records · Page 4Linked to original sources
PubMed1996

Visual-evoked potentials in long-term survivors of acute lymphoblastic leukemia in childhood. The German Late Effects Working Group.

Visual-evoked potentials (VEPs) were studied in 92 asymptomatic long-term survivors of acute lymphoblastic leukemia (ALL) in first complete remission 6-7 years after cessation of therapy in order to detect therapy-related disturbances in conduction velocity capacities within central nerve fibers. Subjects were grouped with respect to CNS prophylaxis: a) ith. MTX and 18 GY cranial irradiation (group A, n = 58), b) ith. MTX and iv. MHD-MTX, no cranial irradiation (group B, n = 34). At follow-up VEPs were abnormal in 10 subjects (10.9%) with comparable rates in both CNS prophylaxis groups (A: 7/58 [12.1%], B: 3/34 [8.8%]; p = 0.56). Participants with radiological signs of leukodystrophy (n = 14), all within the irradiated CNS prophylaxis group showed significantly prolonged P100 latencies and had a 6.1-fold increased relative risk to develop VEP disturbances. No correlation could be established between VEP outcome and illness- or treatment-related parameters. VEP outcome was not correlated with age at diagnosis or gender. Thus, VEP recordings showed a close relationship with radiation-induced CNS white-matter disturbances. However, their value for clinical practice, routinely performed follow-up evaluations or standardized posttreatment surveillance studies is negligible.

Age of Onset↗
PubMed1996

bcl-2 expression, p53 accumulation, and apoptosis in ovarian carcinomas.

Because little is known about the importance of apoptosis and its regulation in epithelial ovarian cancer, the authors looked for bcl-2 expression and p53 accumulation by immunohistochemistry in 148 ovarian carcinomas of different histologic types and stages. The number of apoptotic cells was assessed in situ by enzymatic detection of DNA fragmentation. Strong bcl-2 expression correlated with low histologic grade (P = .004) and was most often seen in endometrioid carcinomas (P = .001), whereas p53 accumulation was predominantly found in serous and undifferentiated carcinomas (P <.001) and high grade tumors (P <.001). p53 accumulation was associated with advanced tumor stage (P <.001) and the presence of residual disease after surgery (P <.001). Apoptosis increased with histologic grade (P = .012); apoptotic cells were sparse or absent in tumors of low malignant potential and mucinous carcinomas, but found in all other carcinoma types (P = .001). Apoptosis, bcl-2 expression, and p53 protein accumulation were not correlated with each other. The analysis of the postoperative course of 110 patients showed that survival depended on histologic tumor type (P = .0037), histologic grade (P = .0143), FIGO (International Federal of Gynecology and Obstetrics) stage (P = .0001), and absence or presence of postoperative residual tumor mass (P = .0001). p53 accumulation was also associated with adverse prognosis (P = .0001). However, bcl-2 positive carcinomas who had a statistically significantly better outcome than patients with p53 positive and bcl-2 negative tumors (P = .0443). Regarding FIGO stage and p53 alone in a Cox model, p53 proved to contribute additional prognostic information both in FIGO stages I/II as well as in FIGO stages III/IV. Thus, our observations point to different molecular alterations possibly underlying phenotypic diversity of ovarian carcinomas and provide clues for a better understanding of tumor progression in these neoplasms. Apoptosis plays a role in ovarian carcinomas, but seemingly is regulated in a different way than in nonneoplastic tissues.

Adenocarcinoma↗
PubMed1996

Isolation of Mycoplasma conjunctivae from conjunctival swabs of Alpine ibex (Capra ibex ibex) affected with infectious keratoconjunctivitis.

Mycoplasma conjunctivae was isolated four times from the eyes of nine Alpine ibex (Capra ibex ibex) suffering from keratoconjunctivitis. The animals examined were affected in two different outbreaks in the Swiss Alps. Parasitological and bacteriological studies, including investigations for chlamydia and mycoplasmas, were performed. The results indicate that M. conjunctivae is the primary pathogenic agent causing infectious keratoconjunctivitis in this species.

Animals↗
PubMed1996

Interphase cytogenetic analysis of serous ovarian tumors of low malignant potential: comparison with serous cystadenomas and invasive serous carcinomas.

The cytogenetic and molecular genetic changes in serous tumors of low malignant potential (LMP) of the ovary have not been well characterized so far. Therefore, we analyzed 20 serous tumors of LMP, 10 invasive serous ovarian carcinomas, and 7 benign serous cystadenomas by nonisotopic in situ hybridization (seven different centromere-specific probes) as well as by flow and image DNA cytometry and compared the data with results of p53 and Ki67 immunohistochemistry, MYC DNA PCR analysis and with the clinical follow-up. All but two tumors of LMP were DNA cytometrically diploid; 9 of 10 invasive carcinomas proved to be DNA nondiploid (p < 0.0001). Nonisotopic in situ hybridization revealed a mean number of 1.5 chromosomal aberrations in tumors of LMP, which differed statistically significantly from cystadenomas (mean, 0.4) and from invasive carcinomas (mean, 3.4) (rho < 0.01). The main changes in tumors of LMP were +6 (7 of 18 cases) and +7 (6 of 19) followed by -3 (5 of 20), -1 (4 of 17) and +X (3 of 20). In the group of invasive carcinomas, the number of cases with signal gains for chromosomes 6 (5 of 8), 7 (7 of 10) and X (4 of 10) and signal loss for chromosome 1 (4 of 9) was even larger. In addition, statistically significantly more cases showed gain of 8 (5 of 10) and loss of 17 (5 of 10) (p < 0.05). Proliferative activity (Ki67 index) was positively correlated with the number of chromosomal aberrations (p < 0.05). There was no association between changes in the centromere signal number of chromosomes 8 and 17 and MYC DNA amplification and immunohistochemical p53 accumulation, respectively. Clinical follow-up showed prognostic differences between tumors of LMP and invasive carcinomas as expected (rho < 0.001) but did not reveal differences within the group of tumors of LMP with regard to the number or type of the chromosomal abnormalities detected. In conclusion, the patterns of chromosomal gains and losses in serous tumors of LMP and invasive serous carcinomas of the ovary do not seem random and suggest a close relation between these neoplasms compatible with sequential stages in a multistep model of ovarian carcinogenesis.

Adult↗
PubMed1996

[Long-term results of organ preserving therapy in ovarian carcinoma].

Conservative surgery is of increasing importance in gynecologic oncology. Criteria for conservative surgery are well defined, in spite of this a lot of young women with early ovarian cancer are treated with radically operative procedures. Data of 17 patients below the age of 35 with stage I ovarian cancer and conservative surgery are reported. Only one of 9 patients with epithelial carcinoma relapsed and could be successfully treated with surgery and chemotherapy. No patient died within a median follow up of 8 years. All patients demonstrated intact endocrine function after conservative surgery.

Adult↗
PubMed1995

Characterization of surface lymphotoxin forms. Use of specific monoclonal antibodies and soluble receptors.

Lymphotoxin (LT) is a cytokine related to TNF, found in human systems in both secreted and membrane bound forms. The well characterized secreted form is a trimer of a single protein, LT-alpha, whereas the surface form is composed of a complex between two related molecules, LT-alpha and LT-beta. Because there is a distinct receptor for the complex, the membrane form is believed to signal via events different from those elicited by TNF and secreted LT-alpha. By using a battery of anti-LT-alpha and LT-beta mAbs, it is clear that two LT surface forms exist on the surface of PMA-activated II-23 cells, a human T cell hybridoma. Assuming that these surface forms are trimers, a minor form appears early after induction having an apparent stoichiometry of LT-alpha 2/beta 1 and is recognized by one group of anti-LT-alpha mAbs and the p55-TNF receptor. The second and predominant form has an apparent LT-alpha 1/beta 2 composition and is recognized by a second group of pantrophic anti-LT-alpha mAbs and the LT-beta receptor. Neither of the heteromeric forms nor a putative LT-beta homotrimeric form were found to be secreted. The properties of surface LT on the II-23 cell system were similar to those of the surface LT forms on Chinese hamster ovary cells transfected with both LT-alpha and LT-beta genes and a number of lymphoid tumor lines. These experiments point toward the LT-alpha 1/beta 2 complex as the predominant membrane form of LT on the lymphocyte surface, and this complex is the primary ligand for the LT-beta receptor.

Amino Acid Sequence↗
PubMed1995

Immunomodulation by LFA3TIP, an LFA-3/IgG1 fusion protein: cell line dependent glycosylation effects on pharmacokinetics and pharmacodynamic markers.

LFA3TIP, a fusion protein comprised of the first extracellular domain of LFA-3 fused to the hinge, CH2, and CH3 domains of human IgG1 inhibits responses of human and non-human primate T cells in vitro. In seeking to optimize the expression efficiency to prepare large quantities of LFA3TIP for primate studies, the protein was produced in both the CHO (Chinese hamster ovary) and murine NS-0 myeloma cell lines. Although LFA3TIP derived from these cell lines performs identically in vitro in CD2 receptor binding and T cell assays, examination of a pharmacodynamic marker-the reduction in CD2+ lymphocyte numbers-following the administration of equal doses of NS-0 or CHO derived LFA3TIP to baboons, suggested that the effect of the NS-0 derived material was less sustained. Pharmacokinetic analysis of the materials in baboons and mice shows that LFA3TIP produced by NS-0 cells is rapidly cleared from circulation relative to the product derived from CHO cells. The disparate clearance profiles correlate with distinct glycosylation patterns, with LFA3TIP derived from NS-0 cells being less extensively sialylated than that from CHO cells due in part to alpha-galactosyl capping of selected lactosamine moieties in the N-linked glycans of NS-0 derived LFA3TIP. Moreover, enzymatic desialylation of CHO derived LFA3TIP results in a glycoprotein with an evanescent serum profile when administered to mice and baboons. These results correlate the extent of N-acetylneuraminic acid capping with the clearance rates of LFA3TIP derived from the two distinct cell lines, and underscore the importance of evaluating glycosylation dependent PK parameters when choosing production cell lines for recombinant immunotherapeutics.

Adjuvants, Immunologic↗
PubMed1994

Mechanism of lymphocyte function-associated molecule 3-Ig fusion proteins inhibition of T cell responses. Structure/function analysis in vitro and in human CD2 transgenic mice.

Soluble ligands specific for cell surface molecules involved in APC-T cell interactions can signal cells and modulate immune responses. Recently, we reported that LFA3TIP, a fusion protein comprised of the first LFA-3 extracellular domain fused to the hinge, CH2, and CH3 regions of a human IgG1 inhibits proliferation of human T cells in vitro. We report herein the cell-based mechanism(s) of LFA3TIP in inhibition by studying the effects of structurally altered LFA3-Ig fusion proteins on proliferation of human PBL in vitro and on responses of mice transgenic for human CD2. We show that LFA3TIP inhibition requires expression of both the LFA-3 and CH2 domains of the fusion protein that bind CD2 and Fc gamma RI or Fc gamma RIII, respectively. LFA3TIP forms an intracellular Fc gamma R/CD2 bridge and directs cytolysis of CD2+ cells by freshly drawn human PBL in vitro as well as the non-C-mediated depletion of peripheral T cells of human CD2 transgenic mice. The cell-based mechanism(s) of LFA3TIP inhibition are discussed.

Animals↗
PubMed1994

Effects of triphenyltin on fish early life stages.

Using a static-renewal procedure, effects of triphenyltin chloride (TPT) on hatching, survival, and morphology were assessed in early life stages of European minnows Phoxinus phoxinus. Embryonic-larval exposure at 16 and 21 degrees C, and larval exposure at 16 degrees C were compared. In the embryonic-larval exposure at 16 degrees C, hatching was delayed and hatching success decreased at 15.9 micrograms/L. Mortality increased at > or = 3.9 micrograms/L TPT, and complete mortality occurred after 7 and 9 days at 15.9 and 5.1 micrograms/L, respectively. Mortality was higher at 21 degrees C that at 16 degrees C. Triphenyltin was more toxic to fish in larval stages. The induced effects were dose related, mortality increased at 1.8 microgram/L after 3 days, and was total after 5 days at 10.6 micrograms/L. In all high TPT exposures, larvae developed skeletal malformations (bent tails), showed impaired swimming behavior or paralysis, and eyes became opaque. Marked histopathological alterations were found. Degenerative hydropic vacuolation of the cytoplasm were evident in skeletal muscles, skin, kidneys, corneal epithelium, lens, pigment layer of the retina and choroid, retina, and CNS including spinal cord. In severe cases, nuclear changes including pycnosis and karyorrhexis occurred. The observed toxicity of TPT was similar to that of tributyltin, but TPT acted more selectively on the lens and CNS, whereas other tissues were less affected. The study indicates that Phoxinus phoxinus larvae are negatively affected at peak TPT concentrations found in polluted environments.

Animals↗
PubMed1994

The effects of an immunomodulatory LFA3-IgG1 fusion protein on nonhuman primates.

LFA3TIP, a fusion protein comprised of the first extracellular domain of LFA-3 fused to the hinge, CH2 and CH3 domains of human IgG1, inhibits proliferation of human T cells in vitro. LFA3TIP also inhibits responses of human CD2 transgenic mice by rapidly and totally depleting peripheral T cells. These effects require binding of the LFA-3 and CH2 domains of LFA3TIP to CD2+ T cells and Fc gamma R+ accessory cells, respectively. As CD2 is well conserved in primate species, we evaluated the effects of LFA3TIP in nonhuman primates. We report in vitro results leading to the selection of the baboon as a model for analysis of LFA3TIP, and in vivo effects of single and multidose regimens of LFA3TIP administration. This is the first report of the in vivo administration of an immunomodulatory fusion protein to primates. LFA3TIP is shown to mediate effects on primate T lymphocytes without apparent related toxicities or immunogenicity. Results are discussed in context of potential mechanisms of LFA3TIP immunotherapy.

Adjuvants, Immunologic↗
PubMed1994

The viscosity of red blood cell membranes in patients with beta-thalassaemia.

The purpose of this work was to study the viscoelastic behaviour of the red blood cell membrane (RBCM) in cells from patients with beta-thalassaemia and to investigate whether the precipitated haemoglobin, which is one of the main features of thalassaemic syndromes, influences the membrane viscosity. RBCM viscosities were determined using the micropipet aspiration method. A negative pressure of about 50 Pa was applied in steps at the membrane surface so as to cause partial aspiration of the cell and the entry process was analyzed automatically by a TV-line analyzer. This analysis enabled estimation of the characteristic times (tau 1, tau 2) and corresponding values of the viscosity (eta 1, eta 2). Results were as follows: eta 1 = (1.87 +/- 0.55) microNs/m and eta 2 = (51.42 +/- 20) microNs/m for erythrocytes from normal donors; eta 1 = (3.97 +/- 0.98) microNs/m and eta 2 = (110.40 +/- 35) microNs/m for erythrocytes from patients. Inclusions (Heinz Bodies) were produced artificially in normal cells and the characteristic times (tau 1, tau 2) and corresponding viscosities (eta 1, eta 2) derived in the same manner. For three types of RBC containing increasing numbers of inclusions, the values were: eta 1 = (3.26 +/- 1.70) microNs/m and eta 2 = (77.33 +/- 46.96) microNs/m; eta 1 = (4.21 +/- 1.49) microNs/m and eta 2 = (129.60 +/- 47.90) microNs/m; eta 1 = (7.93 +/- 2.62) microNs/m and eta 2 = (206.60 +/- 93.19) microNs/m. It is concluded that the association of inclusion bodies with the membrane, either in disease or through artificial production, increases the membrane viscosity.

Adult↗
PubMed1993

The ELAM ligand fucosyltransferase, ELFT, directs E-selectin binding to a secreted scaffold protein: a method to produce and purify large quantities of specific carbohydrate structures.

Many biological processes depend on cell surface recognition of receptor-ligand pairs. Some receptors, such as the selectins, recognize specific carbohydrate structures as part of their ligands. The ability to synthesize such ligands for use in the study of cell adhesion mechanisms or as inhibitors of a variety of pathological conditions would be extremely useful. However, the chemical or enzymic in vitro synthesis of carbohydrate-based ligands has thus far been difficult and costly. We have used E-selectin and its carbohydrate ligand as a model system to test if it is possible to express specific carbohydrate structures on a secreted, glycosylated and easily purified scaffold protein and to use this newly modified protein as a functional adhesion molecule. We co-expressed a fucosyltransferase (ELFT) and a secreted immunoglobulin-LFA3 fusion protein (LFA31G) in the same cell to modify the carbohydrate structures on the secreted LFA3IG scaffold protein (we refer to this novel protein as X-LFA3IG). Using glycosidase digestion, lectin binding, carbohydrate composition analysis and antibody-binding assays, we show that approximately 50% of the potential N-linked carbohydrate sites on X-LFA3IG are, indeed, modified and that the modification is the addition of fucose. Furthermore, we show that X-LFA3IG contains epitopes recognized by anti-Slex antibodies, and, using an E-selectin-specific adhesion assay, we demonstrate that X-LFA3IG is a functional ligand for E-selectin. This in vivo approach for generating specific carbohydrate structures could be generalized to produce and purify large quantities of other biologically important carbohydrate structures.

Antibodies↗
PubMed1993

CYFRA 21-1. A new marker in lung cancer.

BACKGROUND: It is known that cytokeratin 19 is particularly abundant in carcinoma of the lung. METHODS: A sandwich enzyme-linked immunosorbent assay called CYFRA 21-1 was, therefore, developed to detect soluble cytokeratin 19 fragments in serum using two specific monoclonal antibodies (Ks 19.1 and BM 19.21). The authors investigated the clinical significance of this new marker compared with the established markers carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), neuron-specific enolase (NSE), carbohydrate antigen (CA) 19-9, CA 125, CA 15-3, CA 72-4, alpha-fetoprotein, and prostate-specific antigen in a pilot study on 1741 serum samples from patients with various benign and malignant diseases. RESULTS: Postulating a specificity of 95% versus benign diseases of the lung, the diagnostic sensitivity of CYFRA 21-1 in lung cancer (independent of histologic type) at primary diagnosis was superior (47%) to CEA (27%), SCC (15%), and NSE (16%). Especially in squamous cell carcinomas of the lung, the true-positive test results were much higher for CYFRA 21-1 (60%) than for CEA (18%) or SCC (31%). CONCLUSIONS: In small cell lung carcinomas, NSE was confirmed as the marker of first choice. For all of the other solid tumors investigated, CYFRA 21-1 showed no better profile of specificity and sensitivity than the established markers.

Antibodies, Monoclonal↗
PubMed1993

Specific interaction of lymphocyte function-associated antigen 3 with CD2 can inhibit T cell responses.

Accessory cell surface molecules, such as T cell antigen CD2 and its ligand lymphocyte function-associated antigen 3 (LFA-3; CD58), are critical costimulatory pathways for optimal T cell activation in response to antigens. Interaction of CD2 with cell surface LFA-3 not only increases T cell/accessory cell adhesion, but also induces signal transduction events involved in the regulation of T cell responses. In this report, we show that specific interactions of LFA-3 with CD2 can result in T cell unresponsiveness to antigenic or mitogenic stimuli in vitro. By deletion of certain regions of the extracellular domain of LFA-3, we localized the CD2 binding site to the first domain of LFA-3. We then demonstrated that a soluble, purified first domain-LFA-3/IgG1 fusion protein (LFA3TIP) interacts with CD2 and binds to the same CD2 epitope as purified multimeric or cell surface-expressed LFA-3. LFA3TIP inhibits tetanus toxoid, hepatitis B surface antigen, anti-CD3 mAb, Con A, and phytohemagglutinin P-induced T cell proliferation, as well as xenogeneic and allogeneic mixed lymphocyte reactions (MLR). Unlike anti-LFA-3 or anti-CD2 monoclonal antibodies (mAbs) which inhibit T cell responses by blocking LFA-3/CD2 binding, LFA3TIP is capable of rendering T cells unresponsive to antigenic stimuli in situations where T cell activation is independent of CD2/LFA-3 interactions. Furthermore, LFA3TIP, but not blocking anti-CD2 mAbs, is capable of inducing T cell unresponsiveness to secondary stimulation in allogeneic MLR. This inhibition of T cell responses by LFA3TIP occurs through a different mechanism from that of mAbs to LFA-3 or CD2.

Animals↗
PubMed1993

Hypnotic hypo- and hyperalgesia: divergent effects on pain ratings and pain-related cerebral potentials.

Pain ratings and pain-related cerebral potentials in response to noxious stimuli were investigated under hypnotic hypo- or hyperalgesia. Out of a sample of 50 subjects the 10 most highly hypnotizable were selected using the Stanford Hypnotic Susceptibility Scale. Phasic pain was induced by brief electrical stimuli intracutaneously applied to the subject's left middle finger. The subjects took part in three experimental sessions. The first session was without hypnosis for familiarization with the experimental surroundings. In the two other sessions, the subjects were hypnotized and given a suggestion of analgesia or hyperalgesia with respect to pain sensation in the left hand. The sequence of hypnosis was matched within and between sessions. Pain ratings and late cerebral somatosensory evoked potentials (SEP) were used to quantify pain reactions. In addition, auditory evoked potentials (AEP) and spontaneous EEG were evaluated to differentiate between pain-specific and unspecific effects of hypnosis. Only the subjects' verbal reports of pain were drastically influenced by hypnosis: suggestion of analgesia diminished the mean pain ratings, suggestion of hyperalgesia enhanced them (P < 0.001). In contrast, the amplitudes of the late somatosensory potentials evoked by the pain-inducing stimuli were not modified in either of the suggestive states. Furthermore, no effects of hypnosis were found on AEPs and on the power spectra of the spontaneous EEG. The results are discussed on the basis of a dissociation of sensory and affective components of pain under hypnosis.

Adult↗
PubMed1993

[The value of reoperation in the treatment of ovarian cancer].

Recurrent ovarian cancer is still a significant problem despite intensive primary therapy, consisting of radical surgery and subsequent chemotherapy. The primary reason for consequent follow up investigations and immediate start of second-line therapy in cases of recurrence is based on the fact, that patients with relapse more than 12 months after primary therapy have a mean survival of 105 weeks after diagnosis. The value of surgical treatment is controversially discussed in the literature. Several authors argue, that there is no definitive prolongation of survival. Between January 1984 and July 1990, 285 patients presented themselves at our hospital with recurrence or progression of ovarian cancer. 72 of these patients had surgical treatment and those patients are part of the investigation. The mean survival of the patients (n = 18), which were operated with no remaining tumour, was 166 weeks. The average survival time of the 22 women with up to 2 cm remaining tumour was 108 weeks. The average survival time of the 32 patients with more than 2 cm after surgery was 72 weeks. One important criterion for the achievable tumour-free situation after surgery was the distinction between primary progression and relapse, where relapse was defined as recurrence more than 12 months after primary treatment. 29% of the patients with relapse could be operated tumour-free, a situation which could be achieved only in one of 13 patients (8%) with primary progression of the disease. Surgery in recurrent ovarian cancer is only indicated in patients with relapse more than 12 months after primary surgery. Tumour-free patients have significant benefit from the surgical procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

[Value of tumor-reductive secondary operation (interventional laparotomy) in ovarian cancer].

Only 20-50% of patients with advanced ovarian cancer have minimal residual disease after aggressive primary cytoreductive surgery. For patients with residual tumour, responding to platinum-based chemotherapy, new therapeutic procedures should be attempted. In most cases, the benefit of performing secondary surgery could not be clearly demonstrated. But there is a consensus of opinion that a second-look procedure in order to confirm complete remission does not improve survival. Between January 1984 and July 1990, 346 patients with primary ovarian cancer were treated at our institution. 190 patients underwent secondary surgery, 93 of these had secondary debulking and are part of the study. After secondary cytoreductive surgery 38 patients (41%) had no residual disease, 35 patients (38%) had disease less than 2 cm, and 20 patients (21%) had disease greater than 2 cm. Mean survival in patients with no residual disease after secondary debulking surgery was 46 months and significantly longer as in patients with residual disease. Patients with residual tumour at primary surgery and no secondary cytoreductive operation survived 35 months, with a significant difference to the patients with secondary debulking and no residual disease. Secondary debulking surgery should be performed in all patients in whom minimal residual disease can be achieved. Preoperative diagnostic tools, including CA 125 value, computed tomography and immunoscintigraphy, should predict a tumour-free situation after secondary cytoreductive surgery.

Adult↗