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M Hoffman

Publications and source records attributed to M Hoffman.

At least 199 records · Page 11Linked to original sources

Platelets contain releasable coagulation factor IX antigen.

Platelets take up plasma proteins into their alpha granules. Platelet activation releases the alpha granule contents. The goal of this study was to test the hypothesis that human platelets also contain some coagulation factor IX in their alpha granules. Platelets were examined by immunofluorescence microscopy. Activated and unactivated platelets were quick frozen on to slides and dehydrated in situ to preserve optimal morphology. The slides were stained by indirect immunofluorescence for factors V and IX. Unactivated platelets showed coarsely granular staining for factor V and finely granular staining for factor IX. Staining for factor V was diffuse after activation, while staining for factor IX disappeared. Thus, the results support the conclusion that platelets contain factor IX which can be released upon activation. Immunoelectron microscopic studies were conducted to more precisely localize the site of the platelet factor IX. As expected, factor V was primarily localized in the alpha granules of unactivated platelets. By contrast, factor IX was observed both in alpha granules and diffusely in the platelet cytoplasm and membrane-bounded vesicles. After activation, staining for both factors V and IX was primarily in the open canalicular system. The physiological importance of this small amount of factor IX is unknown. However, it may be significant since only a few percent of normal IX levels are required to support haemostasis in the absence of trauma, and platelet factor IX could be released at sites of active coagulation.

Antigens↗

[Factors influencing survival in patients with coronary disease. I. Characteristics of examined patients and survival curves].

The group of 683 patients with the significant narrowing (> 70%) of at least one coronary vessel diagnosed by coronarography performed between 1976-1988 in the Institute of Cardiology in Warsaw was followed during one to seven years. The number of patients with a poor left ventricular function was high in the group treated surgically and non surgically. Ejection fraction < 50% was found in 27% and 43% respectively, LVEDP > 12 mmHg (66% and 69%), EDVI > 100 ml/m2 (58% and 70%). Survival curves were calculated in the two different subsets of patients treated surgically and non surgically. Despite some favorite trend toward a better outcome for patients treated surgically the differences were not statistically significant for a whole group. However we showed a significantly higher probability of survival in the subgroup of the three vessel disease treated surgically compared to other treatment. There were no significant differences in survival in patients with one, two, or three vessel disease treated surgically (survival probability of 0.82; 0.78; 0.84 respectively after 7 years). In patients treated non surgically the growing number of diseased vessels worsened the prognosis (survival probability of 0.84; 0.78; 056 respectively). In our observation the differences for better outcome in patients with poor left ventricular function treated surgically did not reach a statistical significance.

Coronary Angiography↗

[Factors influencing survival in patients with coronary heart disease. II. Multivariate logistic function analysis].

A group of 683 patients with the significant narrowing (> 70%) of at least one coronary vessel diagnosed by coronarography performed between 1976-1988 in the Institute of Cardiology in Warsaw was followed during one to seven years. Two hundred ninety of them were treated surgically, 393 non surgically. A multivariate logistic function (MLF) analysis of 10 variables is presented obtained from anamnesis and hemodynamic data and their significance upon survival after 2, 4 and 6 years. In the group treated non surgically the number of narrowed vessels was a factor independently significant after 2, 4 and 6 years. After 4 and 6 years the ejection fraction and the left ventricle end diastolic volume index were also significant. In the group treated surgically none of those were significant after 2 years. After 4 and 6 years anamnesis of arterial hypertonia was significant after 6 years also left ventricle end diastolic volume index. Coefficients calculated from multivariate logistic function analysis allow the calculation of probability of survival for an individual patient.

Adult↗

Coagulation factor IXa binding to activated platelets and platelet-derived microparticles: a flow cytometric study.

Factor IX plays a central role in blood coagulation, since it can be activated by either XIa (intrinsic pathway) or tissue factor-VIIa (extrinsic pathway). Activated factor IX (IXa), in a surface-bound complex with factor VIIIa, then activates factor X. Platelets provide the catalytic surface upon which this Xase complex is assembled in vivo. We have used flow cytometry to examine binding of factor IXa to thrombin-activated platelets in the absence of added VIIIa. Platelet-bound IXa and platelet protein GPIb were detected by indirect immunofluorescence staining followed by two-color flow cytometric analysis. Microparticles were identified by their light scattering characteristics. Two binding sites for factor IXa were detected. The high affinity binding site saturated at about 10 nM, with a Kd of 1.6 nM. A second binding curve, with a Kd of about 100 nM, was observed at higher concentrations of IXa. The high affinity factor IXa binding sites comprise about 7% of the total factor IXa binding. Binding to both sites was dependent on the presence of calcium. Thus, we conclude that factor IXa, in addition to its high affinity binding, has a calcium-dependent low affinity association with activated platelets and microparticles. Sims et al, have shown that binding sites for a different coagulation factor, factor Va, are concentrated on microparticles relative to platelet membrane proteins, such as GPIb. GPIb is distributed on platelets and microparticle in proportion to plasma membrane surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗

Stimulation of 5-fluorouracil metabolic activation by interferon-alpha in human colon carcinoma cells.

Interferon-alpha (IFN alpha) increases the cytotoxicity of 5-fluorouracil (FUra) in vitro, and the combination has clinical efficacy against advanced colorectal cancer. IFN alpha treatment of HT-29 colon carcinoma cells induced a greater than two-fold increase in the intracellular levels of the active metabolite of FUra, FdUMP. Using cell extracts from HT-29 cells and FUra as substrate, IFN alpha produced a 1.9- and 8.7-fold increase, respectively, in the activities of uridine phosphorylase and pyrimidine nucleoside phosphorylase (PyNP). Furthermore, the effect was selective for the conversion of FUra to FdUMP, as IFN alpha did not increase the cellular levels of FUTP, nor did it change the extent of incorporation of FUra into RNA (or DNA). IFN alpha also had no effect on thymidine kinase activity, the second step in the activation of FUra. Hence the effect of IFN alpha on PyNP activity is likely a critical biochemical event that modulates the cytotoxicity of FUra.

Adenosine↗