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Biomedical subjects

S Meyer

Publications and source records attributed to S Meyer.

At least 181 records · Page 10Linked to original sources
PubMed1993

Expression and characterization of functionally active fragments of the platelet glycoprotein (GP) Ib-IX complex in mammalian cells. Incorporation of GP Ib alpha into the cell surface membrane.

The platelet glycoprotein Ib-IX complex (GP Ib-IX) is essential for the initial attachment of platelets to the wall of damaged arteries. In this study, an N-terminal fragment of human GP Ib alpha (residues 1-318), containing the ligand binding sites for von Willebrand factor (vWF) and thrombin, as well as the entire human GP Ib alpha were expressed in Chinese hamster ovary cells. The transfected cells secreted a 48- and a 110-kDa protein, respectively, into the supernatant. Both recombinant proteins were purified by immunoaffinity chromatography. The purified proteins bound soluble vWF in the presence of botrocetin as demonstrated in solid-phase binding assays. The dissociation constant (Kd) for 125I-vWF binding to the recombinant 110-kDa protein was 1.2 +/- 0.2 nM as compared with 1.0 +/- 0.3 nM for vWF binding to purified platelet GP Ib-IX. Both recombinant proteins were also retained on thrombin-Sepharose 4B. The 48-kDa protein contained two N-linked oligosaccharide chains. A 125-kDa protein was identified in the lysate of cells transfected with the coding sequence for the entire GP Ib alpha. Trypsin treatment of this protein generated a 110-kDa fragment, whereas the secreted 110-kDa protein remained unchanged. Post-translational removal of the C-terminal transmembrane domain of recombinant GP Ib alpha might have facilitated the secretion of the soluble glycocalicin-like 110-kDa fragment. In addition, flow cytometry and immunofluorescence microscopy demonstrated that the expression of GP Ib alpha alone is sufficient for its incorporation into the cell surface membrane. These data indicate that two soluble fragments of human GP Ib alpha with binding activity for vWF and thrombin can be expressed in mammalian cells and that the incorporation of GP Ib alpha into the surface membrane does not depend on co-expression with GP Ib beta and/or GP IX.

Animals↗
PubMed1993

Self-renewal and differentiation of normal avian erythroid progenitor cells: regulatory roles of the TGF alpha/c-ErbB and SCF/c-kit receptors.

The c-kit proto-oncogene product is a major regulator of early hematopoiesis in mice. We show here that the avian c-Kit protein, together with the c-erbB protooncogene product, regulates self-renewal and differentiation in two types of normal chick erythroid progenitors. A relatively frequent progenitor expressing only c-Kit transiently proliferated in response to avian c-Kit ligand (stem cell factor [SCF]). A second, rare progenitor coexpressed c-Kit and c-ErbB and was induced to long-term self-renewal by SCF or transforming growth factor alpha (TGF alpha), a c-ErbB ligand. In the absence of SFC or TGF alpha, both progenitors underwent erythropoietin (Epo)-dependent terminal differentiation with indistinguishable kinetics. Interestingly, Epo induced differentiation in the SCF progenitors even when SCF was present. In contrast, the c-ErbB-expressing, TGF alpha-induced progenitors continued to self-renew when treated with Epo plus the growth factors SCF, TGF alpha, or both. Expression of c-ErbB thus may be a dominant determinant for the sustained self-renewal of committed erythroid progenitors.

Animals↗
PubMed1993

Isolation of cytotoxic Kupffer cells by a modified enzymatic assay: a methodological study.

Kupffer cell (KC)-mediated cytotoxicity against tumor cells is of interest, since the liver is a major site of metastatic growth of primary colorectal cancer. KC isolation methods from rat livers, to study the tumoricidal properties of these cells, are based on perfusion of the liver and are therefore not suitable for human KC isolation from liver biopsies. In view of application to isolate KC from small wedge human liver biopsies, we have developed an isolation procedure for rat KC that does not require perfusion techniques. Liver tissue fragments were incubated with pronase with continuous pH registration and neutralization. KC were subsequently separated from other non-parenchymal cells by Nycodenz gradient centrifugation and purified by counterflow centrifugal elutriation. KC and other non-parenchymal cells were identified by immunophenotyping with a cytoplasmic monoclonal antibody ED1 and by ultrastructural analysis. About 3 x 10(6) KC per gram liver were isolated with a final purity of > 95% without loss of viability. To ensure that functionally competent KC were isolated, we assayed cytotoxicity against CC531 tumor cells in a recent developed cell-mediated MTT assay. Maximum cytotoxicity of KC was approximately 40% at an effector to target ratio of 10. In conclusion our approach seems to be a useful and simple method to isolate KC with good functional properties from rat livers, without the need for perfusion techniques.

Animals↗
PubMed1993

Successful alpha-2b-interferon therapy for chronic neutrophilic leukemia.

The authors report two patients with characteristic features of chronic neutrophilic leukemia (CNL) treated with alpha-2b-interferon (IFN) (Schering-Plough). At initiation of therapy, both patients had progressive disease and presented with large tumors. A rapid reduction of the tumor mass and a long-term stabilisation of the myeloproliferative disorder was obtained (therapy duration 16 and 26 months, respectively, and presently ongoing). In one patient, the dose of IFN could be significantly reduced during maintenance without relapse. Neither presented infectious or hemorrhagic complications under therapy. Alpha-2b-interferon is active and safe in CNL, even pretreated and progressive. It can also correct the neutrophil and natural killer functional defects frequently observed in CNL.

Aged↗
PubMed1993

Prolonged retention of high concentrations of 5-fluorouracil in human and murine tumors as compared with plasma.

Concentrations of 5-fluorouracil (5-FU) and its active metabolite 5-fluoro-2'-deoxy-5'-monophosphate (FdUMP) were measured in biopsy specimens of tumor tissue, normal mucosa, metastatic liver nodules, and normal liver tissue obtained from 39 patients and in two murine colon tumors (colon 26 and colon 38) after a single injection of 5FU at a therapeutic dose (500 mg/m2 and 100 mg/kg, respectively). These data were compared with plasma concentrations. Peak plasma concentrations (300-500 microM) of 5FU were comparable in human and murine plasma. The half-life of plasma elimination (during the period from 15 to 120 min) in both mouse and man ranged from 10 to 20 min, whereas at between 2 and 8 h, plasma concentrations varied from 0.1 to 1 microM, the half-life being about 100 min. In both species, 5FU could be measured in plasma at concentrations ranging from 0.01 to 1 microM for several days after 5FU treatment. 5FU concentrations in tissue samples obtained from 14 patients were measured during the time range of 1-6 h, those in samples taken from 7 patients, during the interval of 19-27 h; and those in samples obtained from 18 patients, within the interval of 40-48 h after injection. 5FU tumor concentrations varied between 0.78-21.6, 0.44-6.1, and 0.17-10.8 mumol/kg wet wt., respectively. Some of the 48-h samples were obtained from patients who had received leucovorin plus 5FU; coadministration of leucovorin did not alter 5FU tissue concentrations. At between 4 and 48 h, the tissue concentration/plasma concentration ratio was at least 10. 5FU concentrations in murine tumors were measured for up to 10 days after 5FU administration, with plateau 5FU tumor concentrations being about 50 mumol/kg wet wt. in colon 38 and about 200 mumol/kg wet wt. in colon 26 at 2 h after treatment; after 4 days, values of 0.5 and 4.8 mumol/kg, respectively, were obtained and after 10 days, respective concentrations of 0.1 and 0.07 mumol/kg were detected. The FdUMP concentrations measured in colon 26 and colon 38 tumors were 214 and 46 pmol/g, respectively, at 2 h after 5FU administration, and these values subsequently decreased to about 15 pmol/g in both tumors. In human tumors the initial FdUMP concentration ranged from 10 to 1000 pmol/g; at later time points the level of FdUMP was just above the detection limit of the assay. In liver metastases, high 5FU concentrations seemed to be related to high levels of FdUMP, which was likely of importance for the antitumor effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Enhanced tumour growth in the rat liver after selective elimination of Kupffer cells.

The evidence that Kupffer cells are capable of controlling metastatic growth in the liver in vivo is largely circumstantial. The best approach when studying natural cytotoxicity activities of Kupffer cells is to investigate the effect of Kupffer cell elimination on tumour growth. Until now it has not been possible to eliminate Kupffer cells without affecting other cell populations. We have recently developed a new method to eliminate Kupffer cells selectively: intravenous injection of liposome-encapsulated (dichloromethylene)bisphosphonate (Cl2MDP-liposomes) leads to effective elimination of all Kupffer cells, without affecting non-phagocytic cells. Wag/Rij rats were injected with Cl2MDP-liposomes. After 48 h, rats were inoculated with syngeneic CC531 colon carcinoma cells by injection in the portal system. The results show a strongly enhanced tumour growth in the liver of the Cl2MDP-liposome-treated rats. In these animals, livers were almost completely replaced by tumour and had increased in weight, whereas in the control groups only a few (four to eight) small (1-mm) tumour nodules were found. These data show that selective elimination of Kupffer cells results in enhanced tumour growth in the liver, implying that Kupffer cells play a crucial role in controlling tumour growth in the liver.

Animals↗
PubMed1993

Evaluation and significance of the pupillary light reflex in trauma patients.

The pupillary light reflex is an important component of the neurologic examination of the trauma victim. Although the normal reflex can be predictably altered by specific head injuries, a variety of other factors common to trauma patients such as alcohol, illicit drugs, narcotics, paralyzing agents, hypothermia, and orbital or ophthalmic injury can confound the evaluation of the pupillary light reflex. This report reviews the anatomy and neurophysiology of the pupillary light reflex and discusses the impact these confounding variables may have on this key component of the initial trauma evaluation.

Humans↗
PubMed1993

Birth trauma: its effect on the urine continence mechanisms.

Birth trauma is the most important etiological factor in the genesis of stress urinary incontinence in women (SUI). There is a high incidence of SUI during pregnancy, and after delivery SUI persists in a small percentage of women (2-3%). Almost all studies on perineal muscle function reveal decreasing intravaginal pressures in the days after delivery which rarely return to predelivery levels. A few urodynamics studies have demonstrated reduced urethral closure pressures and functional length after vaginal delivery, but the importance of such findings in the genesis of SUI is controversial. Better consensus has been found when pelvic floor neurophysiology was carried out: there is electromyographic evidence of a denervation-reinnervation pattern in the striated urethral sphincter muscle and occasionally prolonged pudendal conduction times when the pudendal nerves are directly stimulated. Histomorphologic studies of the pelvic floor have demonstrated that, in some women, abnormal collagen types are responsible for vaginal prolapse and accompanying SUI. Finally, the great importance of perineal reeducation by electromyostimulation and biofeedback in patients with traumatic pelvic floor pathology may be emphasized, but the importance of its role in the prevention of late SUI development remains to be established by more prospective studies.

Adult↗
PubMed1993

Transformation of chicken bone marrow cells by the v-ski oncogene.

The effect of the v-ski oncogene on the transformation of chicken hematopoietic cells was examined. In initial experiments viruses encoding the v-ski oncoprotein did not transform chicken bone marrow cells. However, whereas viruses encoding the ts-v-sea oncoprotein transform solely erythroid cells, viruses encoding both the v-ski and the ts-v-sea oncogenes were found capable of transforming myeloid cells from the monocytic and/or granulocytic lineages in addition to erythroid cells. Analysis of cell clones transformed by the v-ski/ts-v-sea virus identified one clone that no longer expressed the v-sea protein, indicating that this protein was necessary for the initiation but not the maintenance of transformation. Subsequent experiments testing the effects of various growth factors on transformation of bone marrow cells by the v-ski oncogene product alone identified the avian c-kit ligand (stem cell factor; SCF) as being able to co-operate with the v-ski protein to cause transformation of chicken hematopoietic cells of both myeloid and erythroid lineages.

Animals↗
PubMed1993

Lice on helmeted guinea fowls at five localities in South Africa.

A total of 234 helmeted guinea fowls, Numida meleagris coronata, were examined for lice at five localities in South Africa. These were the Mountain Zebra National Park in the eastern Karoo, Cape Province; the Andries Vosloo Kudu Reserve and the farm Bucklands, in Valley Bushveld, eastern Cape Province; the Bontebok National Park, south-western Cape Province; and the southern part of the Kruger National Park, eastern Transvaal Lowveld. A total of eight louse species, comprising Amyrsidea desousai, Clayia theresae, Goniodes gigas, Goniodes numidae, Lipeurus numidae, Numidicola antennatus, Numidilipeurus lawrensis and Somaphantus lusius were recovered from the guinea fowls. With the exception of A. desousai, which was not recovered from the guinea fowls in the Bontebok National Park, all eight species were present on the birds at each locality. The prevalence of infestations on the birds at the various localities ranged from 99.2-100%, and the numbers of lice present on individual birds, from 0-3619. Goniodes spp. and N. antennatus were the most abundant and A. desousai the least.

Animals↗
PubMed1993

[Acute arterial occlusion of the upper extremity by tumor embolism].

We present a case of acute occlusion of the right branchial artery in a 56-year-old male caused by bronchogenic tumor embolus as the first manifestation of malignancy. The primary tumor was shown to be inoperable and rapidly formed metastases in skin and liver. The case presented demonstrates, that embolic events originating from malignant tumor cells are characteristic for organ-exceeding tumor growth. Thus the prognosis is generally poor.

Arm↗
PubMed1993

Anterior vascularized rib strut graft in the treatment of Pott's disease in the young child.

Two young children suffering from acute thoracic kyphosis due to vertebral tuberculosis (Pott's disease) are described. One patient presented with recent onset spastic paraplegia due to cord compression. Anterior decompression and stabilization with a vascularized rib strut graft was performed in both patients. The neurological recovery in the compromised patient was remarkable; spinal stability was achieved in both patients, thus avoiding the necessity for a posterior spinal fusion.

Child, Preschool↗
PubMed1992

[Increasing frequency of soft tissue sarcomas in The Netherlands].

Recent data from literature show an increase in incidence and mortality due to soft tissue sarcoma (STS). In the Netherlands age-standardised mortality rates of soft tissue sarcoma (STS) over the period 1950-1988 show a more than fivefold increase. Males predominate over females by a factor of 1.17. Age-adjusted hospital admission rates in 1980-1988 show an increase by a factor of 1.36. The mean estimated incidence is 4.74 per 100,000 person years over a three-year period (1988-1990). The most prevalent histological types in that period were leiomyosarcoma (20.1%), malignant fibrous histiocytoma (16.2%), Kaposi's sarcoma (13.9%) and liposarcoma (13.8%). The distribution of the different histological types changes in time. The increasing incidence of Kaposi's sarcoma is due to the increasing prevalence of AIDS. Hospital admission rates for STS increased from 0.67% of admission rates for all malignant neoplasms in 1970, to 0.96% in 1988. Further epidemiological studies are needed to elucidate the increase of STS throughout the world.

Adolescent↗
PubMed1992

ATPase state and activity in thylakoids from normal and water-stressed lupin.

To compare with the case of phosphorylation, ATP hydrolysis was investigated in thylakoids from plants submitted to drought. For medium stresses the relationship between hydrolysis rate and deactivation constant of the de-energized enzyme when delta pH varies is unchanged, hence the basic mechanisms are preserved; (PS1-driven) energization than is neither affected, at any light intensity. As drought intensifies, hydrolysis and monogalactolipids fall somewhat in parallel, whereas the deactivation constant changes with digalactolipids and phosphatidic acid content. This alteration of the F0 lipid environment must be transduced to F1, the subunits of which, however, are preserved, as shown by LDS-PAGE. ATP synthesis (thiol-oxidized enzyme) and hydrolysis (thiol-reduced enzyme) show an identical decrease with stress. Thus the latter impairs a common early step, probably the activation of the oxidized enzyme.

Adenosine Triphosphatases↗
PubMed1992

Determination of the DNA sequence recognized by the bHLH-zip domain of the N-Myc protein.

The DNA-binding domain of the murine N-Myc protein, comprising the basic helix-loop-helix-zipper (bHLH-zip) region was expressed as a fusion protein in E. coli. The affinity purified glutathione-S-transferase-N-Myc fusion protein (GST-N-MYC) was used to select the N-Myc specific DNA-recognition motif from a pool of random-sequence oligonucleotides. After seven rounds of binding-site selection, specifically enriched oligonucleotides were cloned and sequenced. Of 31 individual oligonucleotides whose sequences were determined, 30 contained a common DNA-motif, defining the hexameric consensus sequence CACGTG. We confirm by mutational analysis that binding of the N-Myc derived bHLH-zip domain to this motif is sequence-specific.

Base Sequence↗