Search PubMed⌕ Search

Biomedical subjects

G Schuler

Publications and source records attributed to G Schuler.

At least 289 records · Page 16Linked to original sources
PubMed1987

Hereditary suppression of lethal (2) giant larvae malignant tumor development in Drosophila by gene transfer.

Homozygous mutations of the recessive oncogene lethal-(2) giant larvae (l(2)gl) of Drosophila melanogaster cause lethal neoplasms of the imaginal discs and the brain hemisphere. A 13-kb DNA segment spanning the l(2)gl+ locus has been inserted into P element vectors and used for P-mediated transformation. The P-l(2)gl+ transposons have been introduced into the germ line of heterozygous l(2)gl-/+ flies and were shown by backcrossing to fully rescue the homozygous l(2)gl deficient animals, which otherwise would have died of brain and imaginal disc neoplasms. Further genetic backcrossing with l(2)gl deficiencies characterized by deletions of increased sizes involving the left end of chromosome 2 indicated that a relatively large region of developmentally regulated DNA sequence adjacent to the l(2)gl gene is apparently not essential for the viability and fertility of the fly. These experiments indicate that all the genetic information specified by the l(2)gl+ gene is contained within this 13-kb DNA segment and demonstrates that the development of neuroblastomas and imaginal disc tumors results from the absence of l(2)gl function. When this function is restored, tumor development is completely suppressed.

Animals↗
PubMed1986

Immunologic properties of purified epidermal Langerhans cells. Distinct requirements for stimulation of unprimed and sensitized T lymphocytes.

Langerhans cells (LC) are Ia+ leukocytes that account for less than 2% of the cells in murine epidermal isolates. We purified LC by cell sorting to study their capacity to stimulate antigen-specific responses from unprimed and sensitized T cells. Sorting was performed after 12 or 72 h of epidermal culture, since our earlier work had indicated that LC became immunologically active during that time interval. At 12 and 72 h, the LC were uniformly and equally rich in the Ia glycoproteins that are recognized by helper T cells. At both time points, LC were comparable in their capacity to stimulate sensitized helper T lymphocytes, and would cluster the T cells in an antigen-dependent fashion at 4 degrees C. However, 12-h LC did not sensitize T cells, as indicated by their inactivity in stimulating the primary MLR or antibody response, and they were unable to cluster T cells in an antigen-independent fashion at 37 degrees C. The latter properties were acquired during 72 h of culture. As a result, the function of 72-h LC fully resembled that of lymphoid dendritic cells. We propose that the maturation of stimulatory function within the dendritic cell lineage represents an important control point in the induction phase of cell-mediated immunity.

Animals↗
PubMed1986

[Reinfarction after initially successful thrombolysis in acute myocardial infarct].

UNLABELLED: In 24 of 77 patients (31%, group A), successfully treated by intracoronary streptokinase infusion in the acute stage of a transmural myocardial infarction, reocclusion of the infarct artery occurred within four weeks, in 15 patients with, in the remaining nine without re-infarction symptoms. The age of the patients, frequency of single, double or triple-vessel disease, number of anterior and posterior wall infarcts, creatine-kinase activity before and during treatment, and degree of stenosis at first contrast-medium injection were all comparable in the patients with or without re-occlusion (53 patients, group B). At the end of the acute treatment, in five patients of group A (21%) and in 17 of group B (32%) combined with balloon dilatation at the same time as the infusion, residual stenosis was significantly higher in group A than group B (75%) and 62%, respectively; P less than 0.001). No patient with a residual stenosis of less than 50% (18, of whom 12 had balloon dilatation) had a re-occlusion. CONCLUSION: A residual stenosis of at least 50% after initially successful thrombolysis presents a marked re-infarction risk and should lead to a second intervention in such cases.

Adult↗
PubMed1986

Abnormal expansions of granular lymphocytes: reactive lymphocytosis or chronic leukemia? Case report and literature review.

A case of chronic lymphoproliferative disorder is presented, wherein a morphologically homogeneous population of lymphoid cells displayed properties similar to those described for large granular lymphocytes (LGL). Besides their LGL-like phenotype (VEP 13+, OKM 1+, OKT 10+ Fc-IgG-receptor+, OKT 3-), the proliferating cells were cytotoxic to NK targets as well as to antibody-coated target cells. Clinically, our patient presented low-grade lymphocytosis, splenomegaly, neutropenia, hyperimmunoglobulinemia and recurrent infections. Based upon this and 32 similar cases reported in the literature, we conclude that lympho-proliferative disorders involving GL encompass a variety of clinical entities, ranging from reactive GL lymphocytoses to overt lymphocytic malignancies.

Adult↗
PubMed1986

Ontogeny of Ia-positive and Thy-1-positive leukocytes of murine epidermis.

Murine epidermis harbors 2 populations of dendritic leukocytes: Langerhans cells (LC) and Thy-1-positive dendritic epidermal cells (Thy-1 +DEC). In the adult mouse these cell types are morphologically distinct and display highly characteristic phenotypes. LC bear Ia-antigens and a group of markers typical for mononuclear phagocytes: Fc- and C3bi-receptors, macrophage-specific antigen F4/80, and membrane ATPase. Thy-1 +DEC, in contrast, lack these markers but express high levels of Thy-1 and asialo-GM1 (asGM1) antigen. Since LC and Thy-1 +DEC share a common origin from the bone marrow we expected to gain insight into their relationship by studying their ontogenetic development. Epidermal sheets from fetal and newborn C3H/He and C57B1/6 mice obtained at defined ages from day 17 of gestation up to day 30 of postnatal life were monitored for the emergence of the above-mentioned markers for LC and Thy-1 +DEC. In double-labeling experiments LC markers were first detected by visualizing the monoclonal antibodies by a sensitive triple-layer rhodamine-immunofluorescence technique; in a second step, after appropriate blocking procedures, Thy-1 and asGM1 antigens were demonstrated by direct and indirect immunofluorescence. We found that in fetal epidermis, only few cells expressed either Thy-1 or Ia (4 and 1 cells/mm2, respectively, on day 18 of gestation). The bulk of Thy-1 +DEC and Ia +EC appeared only after birth. Adult proportions of Thy-1 +DEC and Ia +EC were reached at around 1 month of postnatal life. In contrast, all the other LC markers were expressed on a substantial number of fetal dendritic cells (280 cells/mm2 on day 18 of gestation), indicating the presence of phenotypically immature Ia-negative LC in fetal epidermis. By day 4 of postnatal life all F4/80 +EC and ATPase +EC (i.e., LC) had acquired Ia-antigens. Surprisingly, LC also bore asGM1 antigens, which in the adult epidermis are strictly confined to Thy-1 +DEC, up to day 5 of postnatal life. Thus, LC in fetal and early newborn epidermis are not yet fully differentiated. As they differentiate, they acquire Ia antigens and lose asGM1 antigens. In contrast, a phenotypically immature Thy-1 +DEC population could not be traced with the markers used. Thy-1 +DEC appear to be characterized by a stable phenotype (Thy-1+/asGM1+) throughout their lifetime.

Age Factors↗
PubMed1986

Immediate pigment darkening phenomenon. A reevaluation of its mechanisms.

Proposed mechanisms of immediate pigment darkening (IPD) are controversial. They include photooxidation of "premelanin," changes in the distribution pattern of microfilaments and microtubules, movement of melanosomes to melanocyte dendrites, increased transfer of melanosomes to keratinocytes, and changes in the melanosome distribution pattern in keratinocytes. We investigated the following aspects of IPD: production of IPD by UVA under physiologic and nonphysiologic conditions in fullthickness skin and epidermal sheets; reversibility of IPD in vitro after in vivo and in vitro production; blocking of IPD by disruption of the microfibrillar or microtubular system in vitro; alterations of the cytoskeleton of melanocytes; the melanosome distribution pattern in melanocytes and keratinocytes. The results were as follows: IPD could be elicited in vitro in full-thickness skin and in epidermal sheets. Its production was temperature independent (0 degrees-37 degrees C) and was not inhibited by repeated freezing and thawing, or by formalin fixation. IPD was reversible in vitro under tissue culture conditions but only in viable skin. IPD could not be blocked by substances that disrupt the microfibrillar or microtubular system (cytochalasin B, colcemid, vincristine). As shown with a monoclonal antivimentin antibody, IPD-producing UVA doses did not induce changes in the cytoskeleton of melanocytes. No changes in number and distribution pattern of melanosomes were observed electron-microscopically and by morphometric analysis of EM micrographs. Production of IPD does not depend on the structural and functional integrity of the melanocyte cytoskeletal apparatus and is not confined to viable skin, whereas its reversibility is. The fact that no increased melanosome transfer occurs may explain the lack of a UV protective action.

Cytochalasin B↗
PubMed1986

[EPICO in the treatment of small cell bronchial cancer. 3. Intermediate analysis].

61 patients with untreated small cell lung cancer were treated with a combination of epirubicin 70 mg/m2, cyclophosphamide 1,000 mg/m2 and oncovin 2 mg every 3 weeks. The mean age of patients was 57 years. 51 patients were evaluable. 30 patients were classified to the stage limited disease, 21 patients to extensive disease. 9 complete and 23 partial remissions were achieved (remission rate 64%). The overall survival was 14 months, the mean survival of responders 16 months. 32 patients were alive at the end of the study. Performance status and extent of disease influenced significantly the result of treatment. The cytostatic activity of EPICO is comparable to three other drug combinations. The benefit of EPICO might be the lower cumulative toxicity of epirubicin and therefore enabling a longer duration of treatment.

Adult↗
PubMed1986

Maturation of immune response to insulin. Recruitment of new epitopes by antibodies.

Guinea pigs were immunized with regular insulin in Freund's adjuvant weekly (N = 6) or with NPH insulin daily (N = 10). The concentrations, the affinities, and the sizes of the insulin-immunoglobin G (IgG) antibody complexes were determined by ultracentrifugation. During the immune response to insulin, 7-S complexes were observed after 3 wk, and 10-S complexes were observed after 4 wk (2P less than .05 in each group). "7-S" antibodies were transferred into immunized guinea pigs before the formation of measurable antibody concentrations. The development of 10-S structures was enhanced in outbred Pirbright white guinea pigs (2P less than .05, N = 6) and in inbred strain II l.b.m. guinea pigs (2P less than .05, N = 7). Insulin may act as a monovalent antigen (7 S) after 3 wk and become bivalent after 4 wk (10 S). The change in valency is enhanced by antibody transfer. It reflects the formation of antibodies recognizing new epitopes on insulin.

Animals↗
PubMed1985

[Long-term prognosis of acute transmural myocardial infarct after intracoronary thrombolysis treatment].

Reperfusion of the infarct vessel by a combination of intravenous and intracoronary infusion of streptokinase succeeded in 66 of 120 patients with acute transmural infarction in whom the infusion had been started less than six hours after onset of symptoms. The recanalization attempt failed in 26, and 28 were treated conventionally. Size of the infarct was determined by 201Thallium scanning before and 48 hours after the acute treatment phase. Cox analysis indicated that successful recanalization had a significantly positive effect on the long-term prognosis compared with failed thrombolysis or conventional measures. The perfusion defect (as measured by 201Thallium scan) was identical in all three groups, but after successful recanalization with streptokinase it was significantly smaller than in the other two groups. The improved long-term prognosis is presumably due to a decrease in the size of the infarct.

Aged↗
PubMed1985

The Thy-1-bearing cell of murine epidermis. A distinctive leukocyte perhaps related to natural killer cells.

Bone marrow-derived leukocytes of murine epidermis can express two phenotypes: typical Langerhans cells, which are Ia+ and Thy-1-, and a recently discovered second population that is Thy-1+ and Ia-. To verify that these phenotypes are expressed by two different cell types, and to help understand their lineage and function, we have studied morphology and reactivity with a large panel of antibodies. Dual antibody immunofluorescence combined with electron microscopy showed that Thy-1+ and Ia+ cells were each distributed in a regular fashion and formed adjacent dendritic systems in or close to the basal layer. Double-labeling studies with anti-Ia and a second monoclonal antibody revealed that all Langerhans cells expressed F4/80 (macrophage), Mac-1 (C3bi receptor), and 2.4G2 (Fc receptor), as well as the thymus leukemia (TL) and heat-stable (M1.69/16) antigens. A large fraction expressed S100 and all exhibited membrane ATPase and nonspecific esterase. In contrast, Thy-1+ cells lacked all these features of Langerhans cells, except that a minority were strongly reactive with 2.4G2. Thy-1+ cells also lacked differentiation antigens of most other types of leukocytes, except they were rich in asialo GM1. By electron microscopy, Thy-1+ cells had cytoplasmic granules that were similar in structure and in their aryl sulfatase content to those previously described in natural killer cells. The granules were enlarged in beige mice, suggesting a lysosomal origin, and were present in mast cell-deficient W/Wv mice, indicating no relation to mast cells. We conclude that Thy-1+ epidermal cells are thoroughly distinct from Langerhans cells. On the basis of morphology and phenotype, they may represent a type of tissue natural killer cell. Thy-1+ natural killer cells are now being identified in several nonlymphoid sites, such as gut epithelium and the livers of mice given adjuvants. If Thy-1+ epidermal cells prove to be natural killer cells, it is noteworthy that they represent a resident population regularly distributed in the basal layer of all mouse strains. The notion that Thy-1+ epidermal cells are immature natural killer cells is intriguing in light of recent evidence that Ia+ Langerhans cells are also immature with respect to accessory cell function. The epidermis may not have the functional capacities of a lymphoid organ, but it could contribute immature cells important for both natural and acquired resistance.

Animals↗
PubMed1985

Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro.

Murine epidermal Langerhans cells (LC) have been studied in tissue culture and compared to spleen dendritic cells (DC). LC comprised 3% of the starting cell suspensions and were distinguished from keratinocytes by cytology and reactivity with anti-Ia and anti-Mac-1 monoclonal antibodies. The LC were nonadherent, had a low buoyant density, did not proliferate, and could be enriched to 10-50% purity. LC continued to exhibit Ia and Mac-1 antigens for 4 d in culture. However, LC rapidly lost Birbeck granules, Fc receptors, F4/80 antigen, and cytochemical reactivity for nonspecific esterase and membrane ATPase. As a result, the ultrastructure and phenotype of cultured LC became remarkably similar to lymphoid DC. Stimulatory capacity for T cell proliferative responses (oxidative mitogenesis and the mixed leukocyte reaction) was monitored daily. Initially, stimulatory capacity was very weak, even though LC expressed substantial levels of Ia antigens. After 2-3 d in culture, LC had become 3-10 times more potent than spleen DC. 30 LC could induce significant responses in cultures of 3 X 10(5) responding T cells. Removal of Ia+ LC at the start of culture ablated the development of stimulatory activity, but exposure to 1,500 rad of ionizing irradiation did not. Mixing experiments showed that contaminating Ia- epidermal cells did not alter the function of Ia+ stimulators. Therefore, LC seem to be immunologically immature, but acquire many of the features of spleen DC during culture. We suggest that functioning lymphoid DC may, in general, be derived from less mature precursors located in nonlymphoid tissues.

Animals↗
PubMed1985

CFU-gm assay, cytochemical and electron microscopic studies in agar in patients with preleukemic syndrome and aplastic anemia.

Thirty-seven patients with chronic cytopenia were studied using a CFU-gm assay in agar. Cell proliferation was evaluated on days 2, 3, 5, 7, and 10 of incubation. Growth patterns were different in cultures of hematologically healthy persons versus patients with preleukemic syndrome (PL) and aplastic anemia (AA). Three types of PL syndrome and two types of AA (C1 and C2) were distinguished. Bone marrow dysfunction was evaluated further using cytochemistry and electron microscopy to morphologically study cell proliferation in vitro. Cytochemical staining performed in agar demonstrated well-defined maturation defects in myelopoietic precursor cells from the bone marrow of PL patients. Electron microscopic findings of Auer-body-like inclusions in "statu nascendi" in the vacuoles of preleukemic cells supported our results. PL patient groups at high risk for development of overt leukemia and patients with grave prognosis in AA were distinguished. Our results are relevant for the clinical diagnosis and prognosis of patients with cytopenia.

Aged↗
PubMed1985

Expression of the Ly-5 alloantigenic system on epidermal cells.

The expression of Ly-5 alloantigens is confined to hemopoietic cell types and is therefore considered a valuable indicator for the bone marrow derivation of a given cell. The further finding that different hemopoietic cell lineages express different molecular forms of the Ly-5 alloantigens prompted us to investigate (1) whether murine epidermal cells or subpopulations thereof express Ly-5 specificities and if so, (2) whether the expression of particular molecular configurations of Ly-5 antigens would allow us to gain a clue about the derivation of certain epidermal cell populations. When epidermal sheets from BALB/c, C57Bl/6, and C3H/He mice, were exposed to monoclonal anti Ly-5.1 antibody in an indirect immunofluorescence technique, a system of evenly distributed, dendritic cells was visualized. Allelic exclusion of the Ly-5 system was demonstrated by replacing anti-Ly-5.1 antibody by anti-Ly-5.2 reagent and by using epidermal sheets from SJL/J mice. Studies on epidermal cell (EC) suspensions revealed that about 1.6-5.2% of C3H/He EC were Ly-5-reactive and that approximately equal numbers of Ly-5-positive cells bore either Thy-1 or Ia antigens. Electron microscopic studies disclosed two morphologically different Ly-5-positive cell populations, i.e., cells of the Langerhans cell lineage and a recently defined cell system, whose most prominent feature is the expression of the Thy-1 antigen. We have termed these cells dendritic Thy-1+EC (dTHY-1+EC). In order to define the molecular configurations of the Ly-5 alloantigens, EC and spleen cells were internally labeled and--after immunoprecipitation of cell-membrane detergent extracts with anti-Ly-5.1--were analyzed on sodium dodecyl sulfate-polyacrylamide gels. Spleen cells yielded 3 bands with a molecular weight of 180,000, 195,000, and 215,000, respectively, as is characteristic for T lymphocytes, non-T/non-B cells, and B lymphocytes. In contrast, a single 195,000-200,000 dalton band was found in precipitates of both untreated and Langerhans cell-depleted (anti-Ia+C) EC. These data demonstrate the existence and active biosynthesis of the Ly-5 alloantigenic system on certain EC populations, i.e., Langerhans cells and dThy-1+EC, and therefore imply that both cell types originate from a bone marrow-derived precursor. The expression of the same molecular configuration of Ly-5 alloantigens on both LC and dThy-1+EC suggest that these two cell populations do not belong either to the T-cell or to the B-cell lineage and imply an ontogenetic relationship between dThy-1+EC and Ia-positive EC.

Animals↗
PubMed1985

Morphological and phenotypical characterization of bone marrow-derived dendritic Thy-1-positive epidermal cells of the mouse.

Increasing evidence exists that the spectrum of dendritic cells within the epidermis is more complex than previously thought. In addition to Langerhans cells, Merkel cells, and melanocytes, the murine epidermis contains a dendritic cell population whose most prominent phenotypic feature is the Thy-1 antigen. These cells are now generally referred to as dendritic Thy-1+ epidermal cells (dThy-1+EC). The ultrastructural features of these cells do not resemble those of other resident epidermal cells (EC). In particular, their cytoplasm contains abundant intermediate-sized filaments of the vimentin type as well as membrane-limited organelles with a central granular core. The bone marrow derivation of dThy-1+EC is now well established: dThy-1+EC carry Ly-5 determinants whose expression is restricted to cells of the hemopoietic differentiation pathway, and studies using Thy-1-disparate radiation bone marrow chimeras have revealed the presence of donor-type Thy-1+ cells within the epidermis; by immunoelectron microscopy, these cells represent dThy-1+EC. dThy-1+EC repopulate the epidermis at a slower rate than Langerhans cells as evidenced by a direct comparison of the repopulation kinetics of both cell systems in radiation bone marrow chimeras, and by experiments studying the emergence of either Ia+- or dThy-1+EC in an epidermis which had been previously depleted of either Langerhans cells (glucocorticosteroids) or of dThy-1+EC (PUVA). The phenotypical features of dThy-1+EC differ from those of thymus-derived lymphocytes, B cells, dendritic cells, and mononuclear phagocytes. The surface marker repertoire of dThy-1+EC (Thy-1, Ly-5, asialo-GM1) resembles certain members of the rather heterogeneous natural killer (NK) cell system but functional studies are needed to ascertain this contention.

Animals↗
PubMed1985

A comparison of murine epidermal Langerhans cells with spleen dendritic cells.

To establish if epidermal Langerhans cells (LC) are related to spleen dendritic cells, we have considered the morphology, phenotype, and function of the 2 cell types in culture. Cultured LC could be partially enriched (up to 50%) on the basis of 2 simple physical properties: nonadherence to plastic, and low buoyant density in dense albumin columns. The morphology of cultured LC and spleen dendritic cells were similar. In particular both cell types had many cell processes and/or veils, and cultured LC lost their distinguishing Birbeck granules. Freshly isolated LC exhibited nonspecific esterase and ATPase, as well as the F4/80 (alpha-macrophage) and 2.4G2 (alpha-Fc receptor) antigens. However all these traits were lost in culture, while Ia and Mac-1 antigens persisted. As a result, the cytochemical and antigenic phenotype of LC became similar to spleen dendritic cells. The one exception was that LC lacked the 33D1 dendritic cell antigen. The function of LC at first differed from spleen dendritic cells in that fresh LC were weak stimulators of T cell proliferation in the mixed leukocyte reaction and in sodium periodate-induced mitogenesis. However, stimulatory activity per cell increased at least 30 fold in culture so that by 2-3 days, LC were 3-10 times more potent than dendritic cells. Maturation of LC function was radioresistant and was accompanied by a small increase in cell surface Ia antigens. Although LC have been likened both to lymphoid dendritic cells and to macrophages, our data suggest a different conclusion. LC seem to be dendritic cell precursors and are immunologically immature. Possibly, lymphoid dendritic cells are in general derived from substantial pools of precursors in nonlymphoid tissues, such as epidermal LC.

Animals↗