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Biomedical subjects

P Schick

Publications and source records attributed to P Schick.

At least 19 recordsLinked to original sources
PubMed1999

Structural and functional characterization of EMF10, a heterodimeric disintegrin from Eristocophis macmahoni venom that selectively inhibits alpha 5 beta 1 integrin.

Alpha5beta1, a major fibronectin receptor, is a widely distributed integrin that is essential for cell growth and organ development. Here, we describe a novel heterodimeric disintegrin named EMF10, isolated from the Eristocophis macmahoni venom, that is an extremely potent and selective inhibitor of alpha5beta1. EMF10 inhibited adhesion of cells expressing alpha5beta1 to fibronectin (IC(50) = 1-4 nM) and caused expression of a ligand-induced binding site (LIBS) on the beta1 subunit of alpha5beta1 integrin. It partially inhibited adhesion of cells expressing alphaIIbbeta3, alphavbeta3, and alpha4beta1 to appropriate ligands only at concentration higher than 500 nM. Guinea pig megakaryocytes expressing alpha5beta1 adhered to immobilized EMF10 and showed extensive spreading and cytoskeletal mobilization. As determined by electrospray mass spectrometry, EMF10 is composed of two species with molecular masses of 14 575 and 14 949 Da, respectively. EMF10 is a heterodimer containing two subunits: EMF10A (Mr 7544 Da) and EMF10B (Mr 7405 and 7032 Da) linked covalently by S-S bonds. Subunit B showed heterogeneity and may be present as EMF10B1 (Mr 7032) and EMF10B2 (Mr 7405). In putative hairpin loops, EMF10A and EMF10B contained CKKGRGDNLNDYC and CWPAMGDWNDDYC motifs, respectively. The reduced and alkylated subunit B of EMF10 inhibited adhesion of K562 cells to fibronectin in a dose-dependent, saturable manner with IC(50) of 3 microM. The synthetic, cyclic CKKGRGDNLNDYC and CWPAMGDWNDDYC peptides expressed their inhibitory activity in the same system with IC(50) of 100 microM. We propose that alpha5beta1 recognition of EMF10 is associated with the MGDW motif located in a putative hairpin loop of the B subunit and that the expression of activity may also depend on the RGDN motif in the subunit A and on the C-termini of both subunits.

Amino Acid Sequence↗
PubMed1989

Antibodies to GM1 and GD1b in patients with motor neuron disease without plasma cell dyscrasia.

Fifty-nine percent of 49 patients with motor neuron disease and 25% of 91 control subjects had IgM antibodies to ganglioside GM1 but usually not to GD1b at titers less than 1:80. This suggests that antibodies to GM1 may be part of the normal human antibody repertoire. However, given the higher incidence of antibodies to GM1 in patients with motor neuron disease, there may be specific epitopes important in antiganglioside antibodies associated with motor neuron disease.

Autoantibodies↗
PubMed1984

Acute radiation injury of mice and the influence of sudden time shift.

The daily light-dark regimen for two groups of mice was advanced by 8 hr. A third group remained in unchanged lighting conditions. At seven different times within the following day subgroups of the time-shifted mice as well as of the group with unchanged time schedule were exposed to whole-body X irradiation. Mortality, body weight, and temperature of each animal were registered for 30 days following exposure and were regarded as indicators of radiation response. Radioresistance was found to be highest after two-thirds of the daily light span, confirming earlier reports by other authors. Well-defined effects of time shift and a corresponding shift of the maximum of radioresistance could be demonstrated. With the individual body weight as an independent variable, mathematical formulas for survival prognosis could be established.

Animals↗
PubMed1983

Preoperative chemotherapy followed by mastectomy for locally advanced breast cancer.

Six patients with advanced local-regional breast cancer were reviewed. Five out of the six patients previously had had radiation therapy as part of the initial therapy. All patients had preoperative cycles of combination chemotherapy, either CMF or CAF. The two stage III patients had greater than 75% reduction in measurable tumor mass, which allowed a conventional modified radical or radical mastectomy to be performed. Both of these patients are now disease free at 26 and 27 months. The four stage IV patients had lesser operations following the chemotherapy (two simple mastectomies, one simple mastectomy plus axillary resection, and one axillary debulking). Reconstruction utilized advancement flaps in three patients and split-thickness skin grafts in the other. None of the patients had postoperative wound problems, and none of the patients had further problems with local cancer control. All patients had combination chemotherapy starting two to six weeks following surgery. Preoperative chemotherapy followed by surgery plays an important role in management of locally advanced stage III and stage IV breast cancer.

Adenocarcinoma↗
PubMed1983

Experimental chemotherapy of radiation injury with synthetic lysophospholipid analogs in mice.

Synthetic lysophospholipids represent a variety of analogs of the naturally occurring 2-lysophosphatidylcholine. Some of these compounds showed significant therapeutic effects on the survival of mice following radiation injury when administered after various doses of whole-body X irradiation. Such therapeutic effects were discernible even when the treatment was given 6 hr after irradiation, and both intravenous and oral application were effective. Intravenous application of 2 X 25 mg/kg lysophospholipid after whole-body X irradiation around the LD50 resulted in significantly higher numbers of surviving animals. The mode of action remains speculative.

Animals↗
PubMed1983

[Therapeutic effect of fetal mesenchyma in acute radiation disease of mice].

The effects of an intramuscular application of fetal mesenchym (Resistocell) in mice with acute radiation injury was investigated. A single dose of 80 mg/kg body weight one day after radiation exposure (LD70/30, 635 cGy) showed significant therapeutic effects. Further experiments are recommended in order to improve and explain the reported results.

Animals↗
PubMed1982

Aspiration cytology is superior to Tru-Cut needle biopsy in establishing the diagnosis of clinically suspicious breast masses.

Eighty-one consecutive patients with breast masses clinically suspicious for malignancy were evaluated prospectively. There were 31 benign lesions and 50 malignancies. Clinical diagnosis was correct in 85% (2.5% false negative, 12.5% false positive). Mammography was diagnostic in 52.8% (31.5% false negative, 15.7% false positive). Needle biopsy was accurate in 78.9% (21.1% false negative, 0% false positive). Aspiration cytology was diagnostic in 96.2% (3.8% false negative, 0% false positive). Statistical comparison of all four tests revealed that aspiration cytology was slightly more accurate than physical examination for all lesions (p = 0.07), but significantly more accurate for benign lesions (p = 0.005). Overall, aspiration cytology was significantly more accurate than mammography (p = 0.000001) and needle biopsy (p = 0.008). Only one minor complication, a superficial infection, occurred with aspiration cytology and needle biopsy. Thin-needle aspiration cytology is a benign procedure that appears to be superior to physical examination, mammography, and needle biopsy in establishing the diagnosis of clinically suspicious breast masses.

Adult↗
PubMed1981

Aspects of cellular proliferation during follicular atresia in the dog ovary.

Autoradiography after pulse labelling with [3H] thymidine was applied to investigate the proliferation processes in the granulosa and theca related to follicular atresia of the dog ovary during metestrus. The number of proliferating cells depends on the follicle type and its atretic stage. There is less proliferation in smaller secondary follicles than either in larger ones or tertiary follicles. While in early atresia tertiary follicles show the highest labelling indices, in advanced atresia the largest secondary follicles are those with the highest values. For each follicle type a decline in the labelling indices can be observed from early to terminal atresia. Tertiary follicles show a precipitous decrease in the labelling index between early and advanced atresia. There is a continuous gradient of proliferation from the center of the follicle over the peripheral granulosa to the theca. In tertiary follicles, an inverse correlation between labelling and necrosis of granulosa cells can be observed.

Animals↗
PubMed1980

Peroperative pancreatic aspiration for evaluating pancreatic disease.

Nineteen patients who underwent peroperative pancreatic aspiration during 1976 to 1978 were retrospectively compared with 19 other consecutively chosen patients who underwent pancreatic surgery without this procedure in 1973 and 1974. In 18 of the 19 patients who had pancreatic aspiration, an accurate diagnosis was obtained. Three patients in the 1973 to 1974 series had serious postoperative complications attributable to incorrect intraoperative diagnosis and subsequent operative therapy. Peroperative pancreatic aspiration cytology provides a definitive diagnosis that may result in the most efficacious therapy for pancreatic disease.

Adult↗
PubMed1979

Estimation of kinetic parameters of neutrophilic, eosinophilic, and basophilic granulocytes in human blood.

Two hematologically normal patients with glioblastoma and six patients with chronic lymphocytic leukemia received continuous 3H-thymidine infusions for 3--10 days. In autoradiographs of blood cell smears taken for 25 days or more after the beginning of 3H-thymidine administration the labeling index and the labeling intensity of granulocytes were determined. A sufficiently high labeling intensity, i.e. a sufficiently long autoradiographic exposure time was found to be critical for obtaining valid and reproducible results. On the basis of certain assumptions discussed in detail, complete labeling of cells with 3H-thymidine followed by autoradiographic evaluation and mathematical analysis of the labeling patterns seems to be a suitable method for estimation of kinetic parameters of postmitotic granulocytes in vivo. The mean intramedullary maturation and storage time was observed to be 115 +/- 7 h or neutrophils, 103 +/- 4 h for eosinophils and 103 +/- 11 h for basophils. The mean relative inflow rate into the blood (or relative turnover rate in the blood) was found to be 4.2 +/- 0.4/h for neutrophils, 4.0 +/- 0.4%/h for eosinophils and 1.2 +/- 0.3%/h for basophils. The mean blood transit time (or blood sojourn time) was estimated to be 25 +/- 2 h or neutrophils, 26 +/- 3 h for eosinophils and 89 +/- 21 h for basophils. Accordingly the half lifes (T 1/2) of granulocytes in the blood were 17.3 +/- 1.4 h for neutrophils, 18.0 +/- 2.1 for eosinophils and 62 +/- 15 h for basophils. Under the quasi steady state conditions of this study the kinetics of granulocytes in the present CLL patients appeared to be normal, despite a marked lymphocytic infiltration of the bone marrow. The apparent discrepancy between these findings and the data obtained with autotransfusion of DFP-labeled granulocytes is discussed.

Aged↗
PubMed1979

[Investigations on combined injuries, 26th communication: investigations on the changes in the state of resistance following sublethal whole-body irradiation (author's transl)].

The risk of a bacterial invasion by pseudomonas, e. coli, proteus, citrobacter and gaffkya via an open skin wound was investigated in combined injured mice (infliction of a skin wound and irradiations). Suspensions of different bacterial strains were applied on the wound and then the lethality was determined. Besides of apathogenic (citrobacter, proteus, gaffkya) and high pathogenic bacteria (e. coli and pseudomonas) an e. coli strain of the 0-Group 81 was found that seems to induce a decrease of lethality even after sublethal whole body irradiation.

Animals↗
PubMed1978

DNA-synthesizing T and non-T cells in chronic lymphocytic leukemia.

In 21 patients with chronic lymphocytic leukemia (CLL) and in 8 hematologically normal persons the number of DNA-synthesizing peripheral blood lymphocytes was investigated by autoradiographic techniques. The lymphocytes were differentiated by EN-rosette tests into T and non-T lymphoid cells. The results show a normal number of proliferating T lymphoid cells and an increased number of proliferating non-T lymphoid cells in clinical stages O-I. Stages III-IV demonstrate a significant increase of the proliferation rate of both T and non-T lymphoid cells. The possible pathogenetic factors and the prognostic value of these results are discussed.

Adult↗
PubMed1978

Labelling of human resting lymphocytes by continuous infusion of [3H]thymidine. I. Characterization of cytoplasmic label.

After continuous 3H-TdR infusion in vivo or incubation with 3H-TdR in vitro human blood lymphocytes were examined by light-microscopic and electron-microscopic autoradiography. Using relatively long autoradiographic exposure times (50--300 days) not only nuclear but also cytoplasmic labelling was visualized, the cytoplasmic label being present in up to 96% of the cells. The cytoplasmic label was predominantly associated with the mitochondria and was removed from the cells nearly completely by treatment with DNase but not with RNase or cold perchloric acid. It is concluded that this cytoplasmic label mainly represents 3H-TdR incorporated into mitochondrial DNA which is continuously renewed in an average turnover time of 14 days or less. This value is compatible with a turnover time of 11 days for mitochondrial DNA in mammalian cells reported in the literature.

Autoradiography↗
PubMed1978

[Study of combined injuries (23rd communication) (author's transl)].

NMRI-mice which were whole-body irradiated, received two or three days later open skin wounds. While irradiation or wounding alone caused a mortality of 10 to 20% and 0% respectively, a combination of injuries caused 80 to 100% mortality. With regard to the as yet unexplained pathogenesis of this clinical condition, bacteriological examination of the skin-wound was undertaken. Staphylococci, lactobacilli and gramnegative bacilli were found on the wounds, and the bacterial concentration per cm2 wound area among animals with combined injuries was significantly higher than in controls. Covering the wounds with lint effected a distinct reduction of bacterial number as well as a reduction of mortality. A similar success of therapy was attained through local administration of antibiotics. A possible correlation between bacterial seeding and increased mortality is discussed.

Administration, Topical↗
PubMed1978

[Cytokinetics of lymph nodes in lymph nodes in lymphatic system diseases (author's transl)].

Untreated malignant lymphatic system diseases are characterized by a preponderance of cell new formation (proliferation) against the destruction of lymphatic cells. If the lymph nodes are enlarged during these diseases, then cell new formation occurs largely or mostly in these lymph nodes. The proliferating cells of the lymph node are bigger than small lyphocytes and have, in general, a mean diameter of the nucleus of 10 mu and more. In normal lymph nodes they belong morphologically to the big lymphocytes, immunoblasts and plasmoblasts. In pathological lymph nodes they have to be looked for among the bigger cells of the disease-specific cell population. Whereas in healthy lymph nodes and in chronic lymphatic leukemia only about 1% of lymph node cells was found to proliferate, they amount on the average to 5% in lymphomas of lymphogranulomatosis and mostly to 30--50% in the lympho-reticulosarcoma (lymphoblast and immunoblast sarcoma, corresponding to large-cell, poorly differentiated lymphomas). The proliferating cells often appear as foci in the lymphomas. The generation times of the proliferating cells both in normal and pathological lymph nodes are about 24 hrs. or slightly longer. In lymphatic proliferation, apart from plasma cells big and smallymphocytes are produced in the normal lymph node; in CLL, big and small lymphocytes, in lymphogranulomatosis, big and small lymphocytes and Hodgkin-cells, and in poorly differentiated lymphomas, the corresponding lymphoma cells are produced. The clinicist is at the beginning of drawing conclusions from prevalent kinetic disturbances.

Cell Division↗