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Biomedical subjects

G Marx

Publications and source records attributed to G Marx.

At least 127 records · Page 7Linked to original sources
PubMed1986

Regulation of thrombin-induced mast cell degranulation by zinc and manganese.

This study was undertaken to determine whether zinc, manganese and copper could regulate the thrombin-induced secretion of the granule-associated mediator, beta-hexosaminidase, from mast cells derived from mouse bone marrow. Exposure of thrombin to copper (2-100 microM) does not affect the enzyme-induced release of beta-hexosaminidase from the mast cells. Zinc at 50 microM reduced the degranulation of calcium ionophore A23187 activated cells by 75% and that of immunological challenge or thrombin by 30% each. Exposure of the thrombin to incremental concentrations of manganese (2-100 microM) prevents its degranulation activity in a dose-related fashion. 75% inhibition of the enzyme activity was achieved at 100 microM manganese. However, exposure of IgE sensitized or unsensitized cells to incremental concentrations of manganese (2-400 microM) prior to antigen or calcium ionophore A23187 stimulation, does not significantly affect the exocytosis of beta-hexosaminidase. The binding of purified human FITC-thrombin to E-mast cells was analyzed by fluorescence flow cytometry. All cells bound specifically the labelled thrombin. Pretreatment of the FITC-thrombin with 100 micron zinc or manganese had no effect on the binding of the labelled thrombin to the cells. It was assumed that manganese modulates either directly the thrombin activity or the substrate for the enzyme on the cell surface.

Animals↗
PubMed1986

Kinetics and differentiation of marrow stromal cells in diffusion chambers in vivo.

Rabbit marrow cells inoculated into diffusion chambers (10(7) cells/chamber) were implanted intraperitoneally into athymic mouse hosts and cultured in vivo for 20 days. A connective tissue consisting of bone, cartilage and fibrous tissues is formed by the stromal fibroblastic cells of marrow within the chambers. Cell kinetics and tissue differentiation have been studied using histomorphometric and biochemical analyses. Haemopoietic cell numbers decrease to less than 0.05% of the initial inoculum during the 20-day period. At 3 days an average of 15 stromal fibroblastic cells only are identifiable within the chambers. After 3 days there is a high rate of stromal cell proliferation with a doubling time of 14.5 h during the period from 3 to 8 days and an increase in the total stromal cell population by more than six orders of magnitude from 3 to 20 days. Thirteen to fourteen population doublings occur before expression of the first observable differentiation parameter, alkaline phosphatase activity. The data demonstrate that the mixture of connective tissues formed within the chamber is generated by a small number of cells with high capacity for proliferation and differentiation. This is consistent with the current hypothesis that stromal stem cells are present in bone marrow.

Alkaline Phosphatase↗
PubMed1986

[Signet-ring-cell lymphoma. Light and electron microscopic study of gastric involvement].

The authors report on a malignant Non-Hodgkin lymphoma of the stomach of a 73-year-old male. Histologically, it was revealed to be a follicularly growing, obviously secondary centroblastic lymphoma. Crystalline cytoplasmic inclusions in numerous centrocytes have led to displacement of the nucleus to the cell margin and thus to the picture of a signet-ring-cell lymphoma. Electronmicroscopically, there were found big crystalline electron-dense deposits in the rough endoplasmic reticulum. The finding was compared with literature data, and the histological differential diagnosis is discussed.

Aged↗
PubMed1985

Fibrinogen coagulation without thrombin: reaction with vitamin C and copper(II).

We describe a novel method for inducing fibrinogen derived clots. The addition of vitamin C (0.1-1 mM) to a solution of fibrinogen (1 mg/ml) and Cu(II) (20-150 microM) results in protein coming out of solution. This phenomenon can be "read" by fibrometers as "clotting time". The reaction requires Cu(II) and can be prevented by a chelating agent, such as citrate, as well by a hydroxyl radical scavenger, such as mannitol. The insoluble protein, called "neofibe", is soluble in 4 M urea and 2% SDS. Isoelectric focusing and SDS-electrophoretic comparison of native fibrinogen with neofibe reveal molecular modifications of the starting protein. This reaction is an interesting example of a free radical mediated transformation of soluble protein into insoluble material. Some findings on the connection between hemostasis, vitamin C and Cu(II) are discussed.

Ascorbic Acid↗
PubMed1985

The procoagulant effect of zinc on fibrin clot formation.

The influence of Zn+2 on fibrin clot formation was investigated by measuring its effect on the clotting times of fibrinogen exposed to thrombin. It was observed with either human or bovine thrombin that 0.01-0.1 mM Zn+2 induced significant reductions of clotting times in a concentration-dependent manner. The procoagulant effect of Zn+2 occurred in the presence of Ca+2 but was inhibited by metal chelating agents. Higher levels of Zn+2 (greater than 0.2 mM final concentration) were required to accelerate thrombin-induced clot formation in the presence of citrate or oxalate. Similarly with oxalated human plasma, greater than 0.2 mM Zn+2 decreased the clotting time. Cations such as Mg+2 and Mn+2 caused little change in clotting times. As an extension of these findings, we examined the effect of Zn+2 on the inhibition of thrombin by antithrombin-III (AT-III). The presence of as little as 0.006 mM Zn+2 in an incubating mixture of thrombin and AT-III severely reduced the inhibitory activity of AT-III towards thrombin. It was observed that the relative intrinsic fluorescence emission of human thrombin decreased upon exposure to Zn+2 but was unaffected by Mg+2 or Mn+2. It is suggested that Zn+2 can form a complex with thrombin, which results in altered reactivity towards fibrinogen and decreased inhibition by AT-III.

Animals↗
PubMed1985

Thrombin-mast cell interactions. Binding and cell activation.

Activation of mouse bone marrow-derived mast cells (BMMC) by thrombin (0.05-0.5 U/million cells) resulted in a concentration-dependent release of histamine, which levelled off by 0.1 U thrombin. Rat peritoneal mast cells (RMC) were not stimulated by thrombin, though in control experiments, both types of mast cells degranulated upon exposure to IgE-antigen. Pretreatment of thrombin with 0.2 mM diisopropylfluorophosphate (DFP), a specific serine protease inhibitor, resulted in 90% loss of thrombin degranulation and coagulant activity. Fluorescently labelled thrombin (FITC-thrombin) specifically bound to the BMMC surface, as measured by fluorescence cytometry. Pre-exposure of the BMMC to 20-fold excess of unlabelled thrombin prior to incubation with FITC-thrombin, prevented the binding of the labelled-thrombin to the cells. Incubation of thrombin with DFP or with antithrombin III (AT-III) resulted in losses of procoagulant and of BMMC degranulatory activities. DFP treatment of FITC-thrombin had no effect on the binding of the labelled enzyme to the cell surface. However, preincubation of the FITC-thrombin with AT-III prevented thrombin binding to the BMMC. Thus, the binding and the catalytic regions of the thrombin molecule are operationally distinct from one another. Kinetic analysis of the BMMC exposed to 0.5 U thrombin revealed a transient rise in intracellular cAMP, which peaked by 15 sec and was not measurable after 1 min. This suggests that differential activation of mast cells can occur at sites of tissue injury.

Animals↗
PubMed1985

Thrombin-induced degranulation of cultured bone marrow-derived mast cells: effect on calcium uptake.

The role of calcium in the mechanism of thrombin activation of bone marrow-derived mast cells (BMMC) was explored by measuring the changes in the uptake of 45Ca2+ into quiescent BMMC and into cells stimulated by thrombin or by IgE-antigen. The results indicate that activation of BMMC by either thrombin or IgE-antigen is Ca2+-dependent. One million BMMC, activated by 0.05-5 U thrombin, accumulated 45Ca2+ in a concentration-dependent manner, which levelled off at around 1 U thrombin. Extracellular 45Ca2+ uptake of thrombin-stimulated cells is saturable within 90 seconds and corresponds to the kinetics of histamine release, whereas that of IgE-antigen exposed cells continues unabated for over 5 min. The pattern of 45Ca2+ uptake of IgE-sensitized BMMC exposed to thrombin suggests that the pro-stimulatory locus of thrombin action on the surface membrane is distinct from that of IgE.

Animals↗
PubMed1985

Zinc-induced platelet aggregation is mediated by the fibrinogen receptor and is not accompanied by release or by thromboxane synthesis.

We demonstrate that zinc (0.1 to 0.3 mmol/L) induces aggregation of washed platelet suspensions. Higher concentrations (1 to 3 mmol/L) of zinc were needed to aggregate platelets in platelet-rich plasma obtained from blood anticoagulated with low-molecular-weight heparin, probably due to the binding of zinc to the plasma proteins. Zinc-induced aggregation of normal washed platelets required added fibrinogen and no aggregation occurred with thrombasthenic platelets or with normal platelets pretreated with a monoclonal antibody (10E5) that blocks the platelet fibrinogen receptor. These data indicate that the platelet membrane fibrinogen receptor-glycoproteins IIb and IIIa mediate the effect of zinc. Zinc-induced aggregation was blocked by the agent TMB-8, which interferes with the internal calcium flux, and by prostacyclin, which elevates platelet cyclic adenosine monophosphate levels. Zinc-induced aggregation was not accompanied by thromboxane synthesis or by the secretion of dense-body serotonin and was not affected by preexposure of platelets to acetylsalicylic acid. Experiments with creatine phosphate/creatine phosphokinase showed that the zinc effect on platelets was independent of extracellular adenosine diphosphate (ADP). Zinc had an additive effect when platelet aggregation was stimulated with subthreshhold concentrations of collagen or ADP. Together with the known effects of nutritional zinc on in vivo bleeding, on platelet aggregation, and on lipid metabolism, the results suggest that zinc may have an important bearing on normal hemostasis, thrombosis, and atherosclerosis.

Adenosine Diphosphate↗
PubMed1985

[Risk-related surgical treatment of colorectal tumors].

By long-time follow-up studies the authors maintain that the prognosis of colonic cancer is determined by distant metastases whereas the prognosis of rectal cancer after surgery for cure is essentially dependent on local recurrences. From that the consideration is derived to improve the prognosis of colonic cancer by an adjuvant chemotherapy, and of rectal cancer by increasing locoregional radicality which can only be attained by preoperative and/or postoperative irradiation. The individual risk of recurrence should be the indicator for an adjuvant therapy in addition to surgery. Some histological signs (grading of the tumour, cellular stromal reaction on the tumour site) correlate with prognosis and risk of recurrence. In this way it seems to be possible to define the high risk cases which may be improved by an adjuvant therapy.

Colonic Neoplasms↗
PubMed1985

[Therapeutic status of stomach cancer in East Germany in 1976 from the surgical viewpoint. A statistical analysis of national and clinical results].

Treatment results are reported about 6 220 cases, registered in the National Cancer Registry of the GDR in 1976. 43.7% had only a symptomatic treatment. 56.0% were operated and only 21.0% were resected. Overall postoperative mortality was 20.6%. Out of these patients resected radically only 24.7% had a 5-year-survival. The overall 5-year-survival rate was 5.1%. Regarding site, stage and surgical methods these results are not satisfying and have to be improved. Therefore, the necessity of regional concentration of gastric cancer treatment is emphasized.

Adult↗
PubMed1984

The inhibitory effect of heparin and related glycosaminoglycans on neutrophil chemotaxis.

Clinical observations have shown that heparin has antiinflammatory activities. The effect of heparin on neutrophil chemotaxis was evaluated in vitro in the Boyden Chamber. This method enabled differentiation between the direct effects of heparin on neutrophil migration and locomotion, and its effects on chemotactic factors. Heparin inhibited both the random migration and directed locomotion of human neutrophils toward zymosan-activated serum (ZAS) and F-met-leu-phe (FMLP). Inhibition was found to be dependent on the concentrations of the heparin and of the chemotactic factors. No specific binding of heparin to the neutrophils could be demonstrated, and heparin's inhibitory effects were eliminated by simple washing of the cells. When added directly to the chamber containing chemotactic factor, heparin inhibited the chemotactic activity of ZAS but not that of FMLP, suggesting a direct inhibitory effect against C5a, the principal chemotactic factor in ZAS. Experiments performed with low-molecular-weight heparin, N-desulfated heparin, dextran sulfate, chondroitin sulfate and dextran indicated that the inhibitory effects of heparin on neutrophil chemotaxis are not related to its anticoagulant activity, but probably depend on the degree of sulfation of the heparin molecule.

Cell Movement↗
PubMed1984

[Relative value of adjuvant nephrectomy in metastatic renal cell carcinoma].

Treatment results were evaluated by 101 cases of kidney-cell carcinomas, and the relative importance of adjunctive nephrectomy discussed. Radial nephrectomy was done in 28.7% and palliative (predominantly adjunctive), in 38.6% of the patients. Postoperatively died 7.6% of the nephrectomized patients. 13.8% of the radically operated survived more than 5 years. The average survival time of the palliatively nephrectomized patients was 12.9 months; it was principally independent of hormonal or cytostatic adjunctive therapy. Furthermore, a case of complete regression of multiple pulmonal metastases after nephrectomy is reported.

Adult↗
PubMed1984

Thrombin-induced degranulation of cultured bone marrow-derived mast cells.

This study was undertaken to determine if a plasma protease such as thrombin, a highly specific procoagulant enzyme that has numerous effects on platelets, endothelial cells, and smooth muscle cells, could mediate mast cell activation processes. Our results indicate that at near physiologic levels, thrombin can rapidly trigger mast cell degranulation without activating the 5-lipoxygenase system.

Animals↗
PubMed1984

[Surgical treatment of bronchial carcinoma].

Surgical resection of the primary tumor along with regional lymph nodes offers the best chance for cure in lung cancer. Progress in thoracic surgery in the past decade has resulted above all from the reduction of operative risk in the elderly, allowing radical operations to be carried out in older patients as well as from better planning of the extent of surgical intervention and avoiding radical intervention where it was not likely to be beneficial. Surgery is indicated as a rule up to tumor stage T3N2M0 , but account must be taken of the patient's functional reserves. Lobectomy, appears to be the method of choice. Segmental resection or tumorectomy may be indicated in patients with limited pulmonary function. Since prognosis depends largely on the tumor's histologic type, more generous indications for surgery are appropriate in the case of squamous cell carcinoma and narrower surgical indications are called for in cases of small-cell carcinoma. Mediastinoscopy allows assessment of regional metastatic spread. Remote metastases should be excluded by liver and one scintigraphy. From 1949 to 1982 a total of 2000 patients with bronchial carcinomas have undergone surgery in the Robert-R ossle -Clinic, with resections having been performed in 1,510 patients. Pneumectomy was performed in 63%, lobectomy in 35% and segmental resection in 2%. Despite broadened indications for surgery post-operative lethality was reduced to 3% during this period. In resected patients who where detected by systematic x-ray screening programs, 5 year survival rates of 38% have been achieved by surgical treatment. Asymptomatic small-cell bronchial carcinomas are cured by operation in 20% of cases. Postoperative empyemas are treated conservatively in our clinic. Further improvements in the prognosis of bronchial carcinoma can be achieved only by early diagnosis and adequate resection.

Aged↗
PubMed1983

[Malignant degeneration of congenital dystopic testes].

About 0.004 percent of the male population were found to suffer from malignant tumors of testicles annually, with undescended testicles being at higher cancer risk than orthotopic ones. An overall statistical analysis of 1,458 cases of congenitally undescended, malignantly degenerated testicles of adults has revealed that 63.18 percent of the patients never underwent drug treatment, while 10.07 percent were treated without success. The remaining 26.73 percent of the patients underwent largely incompetent operations in late adolescence. Six own observations are described briefly. It is recommended to treat congenitally dystopic testicles already in early childhood, which will largely eliminate malignant degeneration of undescended testicles.

Adult↗
PubMed1983

[Early results of the surgical treatment of stomach cancer. Study of 752 patients during the period 1967-1977].

Investigations at 752 patients in the ten-year-period 1967/77. The early results founded out at 752 cases of cancer of the stomach are the following: Operative quote 93,5%, resection for cure 51,2%, postoperative lethality after radical and palliative surgery with elimination of tumour 18,4% and 42,4% respectively. The relations of the lethality to age and kind of operation and the reasons are discussed.

Age Factors↗