Thrombocytopenia after autologous bone marrow transplantation in in acute lymphatic leukemia]

There is reported about the treatment of refractory thrombocytopenia in a 9 years old boy following the autologous bone marrow transplantation for acute lymphoblastic leukaemia. The megakaryocytes were found diminished in the bone marrow smears. Controls of the thrombocyte count and the kinetics with radioactively labeled platelets of a donor spoke in favour of immunothrombocytopenia. Threatening bleeding complications challenged the use of all treatment possibilities. The irradiation of the spleen was without any success. After the splenectomy the thrombocyte count increased slowly, but after a remarkable lag phase, however. A diminished reproduction capacity of the bone marrow graft for special cell sorts has to be taken into account in such cases. The usual cytodynamics after splenectomy cannot be expected at all.     

Apoptosis and necrosis induced by ultraviolet radiation in the presence of autologous plasma

This paper deals with the effect of ultraviolet (UV) light (240–390 nm) at doses of 151–3020 J/m²* on the character of the death of donors’ blood lymphocytic cells (with the use of markers of apoptotic and necrotic cell death) and on the level of the CD95 receptor—a marker of apoptotic predisposition. UV irradiation has been shown to increase the expression of CD95 receptors, which is due mainly to synthesis de novo. It is revealed that over the course of the 24-h incubation of photomodified lymphocytes (at irradiation doses of 151 and 755 J/m²) without autologous blood plasma, cell death occurs by receptor-mediated apoptosis. Action of high irradiation doses (1510 and 3020 J/m²) leads to the massive necrotic death of immunocytes. The use of autologous blood plasma during the incubation of photomodified lymphocytes allows a reduction in the amount of both apoptotic and necrotic cells.     

Effect of continuous irradiation on the thrombopoietic system in mice

In this paper the changes of the megakaryocyte number of the spleen and those of thrombocyte number of the peripheral blood were studied during continuous irradiation with a dose rate of 9.57 to 957 mGy/day. Beginning with a dose rate of 95.7 mGy/day the thrombocyte number of the blood and the megakaryocyte number of the spleen of irradiated animals decreased significantly. Whereas the thrombocyte number remained permanently decreased, the cell number of the megakaryocyte type is increased temporarily to a clearly higher level as compared with the controls on the 100th day of irradiation approximately. This is especially true for the middle dose rate. During this time of irradiation nucleolar hyperchromatosis as well as pycnosis were observed in many megakaryocytes.     

Therapy of severe stenocardia with ultraviolet blood irradiation (UVB) and various action mechanisms of this therapy

We observed 70 male patients with a seriously proceeding Chronic myocardial ischemia. They were hospitalised because of frequent, permanent and serious attacks of stenocardia at rest and in stress situations. More than 2/3 of these patients had suffered from a myocardial infarct. In the course of two weeks an intensive therapy with all modern preparations for vasodilatation was made. This therapy proved to be unsuccessful. Nearly all patients were administered more than 10 tables of nitroglycerin per day and, in addition, they were injected analgetics as a compensation of attack. The ultraviolet own blood irradiation (UVB) had a positive therapeutic effect in all patients. There was a good success in 46 patients, in all patients satisfactory results could be registered. The effect of therapy was evident by the decrease of administration of nitroglycerin required, by an increase in the degree of stress capacity, and by an easier treatment of stenocardia attacks. The observation time for patients amounted to 2-8 months. The success of therapy remained in 38 patients. After this time the success of therapy could partially be regained by a repeated number of irradiation series. Then, it remained positive in 9 of 22 patients who had been followed-up for 10 months. The half decay period of eliminating 131I from an intradermal depot could be normalised under the influence of ultraviolet own blood irradiation. This ultraviolet own blood irradiation had no significant influence on the fibrinogen level, fibrinolytic activity, and erythrocyte aggregation (examined in 11 patients). A 2 1/2-fold diminution of monomer fibrin complexes in the blood could be observed. The titre of antistreptolysin-O was increased in all patients who had got over the infarct. It had completely normalised a week after finishing the ultraviolet own blood irradiation. Spectroscopic examinations of the blood and plasma made after ultraviolet own blood irradiation revealed that this irradiation will not only affect the properties of Hb, but will also cause a photochemical transformation accompanied by a destruction of some plasma proteins, of the membrane of formed blood elements, and a photosynthesis of biochemically active compounds. The mechanism of action of ultraviolet own blood irradiation is complicated and requires further exact investigations. Even today, however, this method can be recommended as a complex therapy in patients with severe myocardial ischemia.     

Treatment of refractory chronic idiopathic thrombocytopenic purpura with high dose intravenous immunoglobulin

Three patients with a history of chronic idiopathic thrombocytopenic purpura stretching back over 20 years are reported. Despite splenectomy and immunosuppressive therapy satisfactory control of their disease has not been achieved. They had remained refractory to all therapeutic manoeuvres with corticosteroids and immunosuppressives for years with thrombocyte counts between 5,000 and 25,000/microliters and the concommitant risk of bleeding. This report describes the treatment of bleeding complications in these patients with high dose intravenous immunoglobulin; the peripheral blood thrombocyte count increased in all three patients from subnormal towards normal, but 2 to 4 weeks later returned to its initial low value. During the therapeutically induced raised thrombocyte count a normal bleeding time and only a moderate inhibition of thrombocyte adhesion and aggregation was observed resulting in reasonable haemostasis. High dose intravenous immunoglobulin is therefore a practical method for the control of bleeding complications in patients with refractory chronic idiopathic thrombocytopenic purpura. A clear explanation for its mode of action has not been found - the lymphocyte subpopulations remained unchanged and immunoglobulin production in vitro during the course of treatment was only minimally decreased.     

Elevation of serum 25-hydroxycalciferol levels in androgen-treated and ultraviolet-irradiated rats.

Administration of 4-8 mg testosterone propionate significantly raised 25-hydroxycalciferol levels in the ultraviolet irradiated rats compared to the ultraviolet irradiated controls, but failed to influence serum 25-hydroxycalciferol levels in the non-irradiated animals. Estradiol benzoate and progesterone did not influence serum 25-hydroxycalciferol levels regardless of the ultraviolet irradiation. These findings implicate that testosterone enhances vitamin D biosynthesis induced by ultraviolet irradiation in rats, in accordance with the clinical observation that males often show higher levels of serum 25-hydroxycalciferol than females.     

Serial studies of autologous antibody reactivity to squamous cell carcinoma of the head and neck

Summary In previous studies we evaluated the incidence and specificity of autologous antibody reactivity against squamous cell carcinoma of the head and neck (SCCHN). We were able to demonstrate that autologous antibody reactivity is present in native sera but was usually of too low a titer to allow further analysis. Dissociation of immune complexes by acidification and ultrafiltration of serum augmented autologous antibody reactivity in nine out of nine autologous systems tested. Native antibody and antibody derived from immune complexes produced by the host and reactive with autologous tumor cells may be directed against physiologically relevant antigens. Therefore, correlations of antibody titers with clinical course may provide insight into the nature of the host response to cancer. In the present analysis, serological studies of six patients with SCCHN were performed with serum samples obtained over many months. Results of serial serological assays were correlated to tumor progression and clinical course. Fluctuations in autologous antibody reactivity were noted over time. In four cases, rises in autologous antibody titers preceded the clinical diagnosis of recurrence by several months. Drops in autologous antibody reactivity were noted in two cases following surgery or radiation therapy. In two cases of long-term survivors, no correlation between antibody reactivity and clinical course was noted. Specificity analysis of the six autologous systems demonstrated reactivity against autologous and allogeneic SCCHN as well as melanoma cell lines. These sera did not react with glioma, neuroblastoma, renal cell, breast, bladder and colon carcinoma cell lines nor with fetal calf serum, pooled lymphocytes, red blood cells and platelets. Autologous serial serological studies may provide a means by which to evaluate the host/tumor relationship in patients with SCCHN.     

Dantrolene protects erythrocytes against oxidative stress during whole-body irradiation in rats

In our study, we examined the radioprotective effects of dantrolene against gamma irradiation-induced damage of blood cells after total body irradiation of rats. Rats were divided into three groups of eight rats each. The first group was the control group receiving no dantrolene or irradiation, the second group received total body irradiation (RT) with 5 Gy of gamma irradiation only, and the third group received dantrolene at a dose of 5 mg x kg(-1) plus RT. Dantrolene was given intraperitoneally 30 min before RT. All groups were sacrificed 2 h after RT, and blood samples were taken. Leukocyte, and thrombocyte counts and hemoglobin levels were measured. Furthermore, malondialdehyde (MDA) levels in plasma and erythrocytes and superoxide dismutase (SOD) and glutathione peroxidase activities (GSH-Px) in erythrocytes were determined. It was found that pretreatment with dantrolene at a dose of 5 mg x kg(-1) significantly reduced the MDA levels and increased the antioxidant SOD and GSH-Px activities, and prevented the decrease in leukocyte and thrombocyte counts. We conclude that dantrolene has clear antioxidant properties when given prior to radiation exposure and the protective effect of dantrolene against damage inflicted by radiation, depends, at least in part, on the decrease in lipid peroxidation and increase in the activity of antioxidant enzymes SOD and GSH-Px.     

Diffusible Fraction of Serum Cholesterol and Atherogenesis

CHOLESTEROL is found in the blood as a structural component of lipoproteins concerned with the transport of other lipids¹. The high resolution nuclear magnetic resonance spectra of high density serum lipoproteins are similar to that observed when lipids are dissolved in organic solvents, or dispersed in water by bile salts or detergents, or in sonicated form. The lipid component in lipoproteins is therefore probably in an extremely fluid condition². If human serum is mixed with paraffin oil, some of the cholesterol diffuses into the oil without affecting the ultraviolet absorption spectrum of serum proteins. This procedure avoids any protein denaturing action used for cholesterol extraction^3–5. It therefore seems that serum cholesterol has two fractions, one strongly bound by lipoprotein structures and the other loosely bound and diffusible in an oil phase. In this article I designate the loosely bound fraction “diffusible”.     

Effect of conditioned medium on recovery of circulating blood cells in irradiated mice.

The effect of supernatant of thymus-cell conditioned medium (TCCM) on blood element recovery in peripheral blood was followed in mice exposed to a single whole body dose of 5.8 Gy of gamma radiation. As follows from our results. TCCM administered 18 h before irradiation accelerated the recovery of the reticulocyte and, in part, thrombocyte and granulocyte counts. However, no effect on the rate of lymphocyte recovery was found.     

齿孔酸对高尿酸血症黄嘌呤氧化酶活性的影响

采用紫外分光光度法检测齿孔酸在体外对黄嘌呤氧化酶的作用,并进行动力学研究探讨其作用机制;采用酵母联合氧嗪酸钾诱导高尿酸血症小鼠模型,观察齿孔酸对高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性及血糖血脂的影响。研究发现,齿孔酸体在外能抑制黄嘌呤氧化酶活性,降低高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性,同时明显降低空腹血糖、总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平,升高高密度脂蛋白胆固醇水平,提高口服糖耐受量。结果表明,齿孔酸是黄嘌呤氧化酶竞争性抑制剂,还能缓解高尿酸血症小鼠糖脂代谢紊乱,对高尿酸血症及痛风的防治具有潜在意义。     

齿孔酸对高尿酸血症黄嘌呤氧化酶活性的影响

采用紫外分光光度法检测齿孔酸在体外对黄嘌呤氧化酶的作用,并进行动力学研究探讨其作用机制;采用酵母联合氧嗪酸钾诱导高尿酸血症小鼠模型,观察齿孔酸对高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性及血糖血脂的影响。研究发现,齿孔酸体在外能抑制黄嘌呤氧化酶活性,降低高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性,同时明显降低空腹血糖、总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平,升高高密度脂蛋白胆固醇水平,提高口服糖耐受量。结果表明,齿孔酸是黄嘌呤氧化酶竞争性抑制剂,还能缓解高尿酸血症小鼠糖脂代谢紊乱,对高尿酸血症及痛风的防治具有潜在意义。     

Changes in erythrocyte and thrombocyte aggregation after ultraviolet irradiation

Lipid peroxidation which occurs in blood serum under ultraviolet irradiation was studied. The products of these reaction suppress ADP-induced aggregation of native platelets. The rouleaux-forming capacity increased after UV-irradiation of plasma and serum albumin. Under UV-irradiation the aggregates of albumin molecules are supposed to form the aggregates of albumin molecules which bind the erythrocytes in rouleaux.     

Effect of u.v. rays on 7-dehydrocholesterol content in rat skin

Long-term exposure of rat to ultraviolet irradiation affected the cholesterol metabolism in the skin. The 7-dehydrocholesterol content was increased to 1.6 times of non-irradiated rat. However, the cholesterol content was not altered. Ultraviolet-induced precholecalciferol and cholecalciferol bound with an activator protein of Δ^5,7 sterol-Δ⁷-reductase. This observation suggested that precholecalciferol and cholecalciferol inhibit the conversion of 7-dehydrocholesterol to cholesterol and accumulate 7-dehydrocholesterol. The action of ultraviolet rays on the cholesterol metabolism in the skin may be explained as the action of ultraviolet-induced preeholecalciferol and cholecalciferol.     

PPIX induced photohemolysis of erythrocytes partially-depleted of cholesterol

The protoporphyrin IX (PPIX)-sensitized hemolysis of erythrocytes depleted of cholesterol was investigated. From 20% to 30% of the total membrane cholesterol was removed from cells by incubation with old autologous plasma or by means of interaction with L-alpha-phosphatidylcholine dipalmitoyl (DPPC) liposomes. As expected, after this treatment, the cells show an overall increase in membrane fluidity revealed by means of specific fluorescent probes. The same cells are more susceptible to the photohemolysis induced by PPIX excited by visible light, but gave no lysis in the absence of the sensitizer. As a consequence, the primary oxidative damage which is produced during irradiation can be possibly assigned to the phospholipidic and/or proteic moiety instead of the steroidal moiety.     

Human autologous rosettes. I. Mechanism of binding of autologous erythrocytes by T cells.

A population of human peripheral blood lymphocytes is able to bind autologous erythrocytes in the presence of autologous serum. Erythrocyte binding is found to be more efficient at 4 °C after preincubation of lymphocytes in autologous serum for 30 min followed by overnight incubation. The overall cellular concentration and erythrocyte/lymphocyte ratio are also crucial in determining the weak erythrocyte binding to autologous lymphocytes. Membrane proteins are involved since the binding structures are sensitive to protease treatment. The 26% RFC obtained with an optimized assay are related to the T-cell lineage.     

Acute and late effects in the course of and after total body irradiation with following bone marrow transplantation in patients with different forms of leukaemia

The acute reaction in the course of a total body irradiation (TBI) appears in an organ-specific damage of the stem cells. Moreover, there are unspecified central-nervous stress reactions. Clinical reactions are obtained by the study and symptomatic therapy is proposed. 90 patients with different forms of leukaemia were observed. We documented the course in a specific "protocol system". Reactions like an increase of body temperature, changes of pulse and blood pressure were registered. The occurrence of gastro-intestinal reactions is a typical symptom of the acute radiation syndrome e.g. vomiting and diarrhoea are demonstrated in dependence of the applicated dose of irradiation. Further symptoms of TBI appeared in the later period. Mucositis, parotitis, a decreased function of the salivary glands and diarrhoea as well as vomiting are characterized by different intensity and temporary termination. A difference between allogeneic and autologous transplantation is caused by a medicamental additional treatment. During the late period these symptoms will disappear completely. Moreover, after TBI and BMT late effects are a cataract and some changes in the hormonal system demanding a specific correction or substitution respectively.     

Effect of thrombopenia on bone marrow CFU-S level and its capability to modify the circulating thrombocyte number

Thrombocytopenia (rise of the thrombopoietin level) was induced by an antithrombocyte serum in mice. After 6 hours of existence of thrombocytopenia, the CFU-S and megakaryocyte-commmitted stem cell content of the bone marrow and spleen was determined by transplantation into mice pretreated with 800 cGy-rtg irradiation. Thrombocytopenia did not influence the CFU-S content. Thrombocytopoiesis of the recipient mice was better restored by bone marrow and spleen cells of thrombocytopenic animals than by cells transplanted from animals with a normal thrombocyte count.     

Treatment of autoimmune disease with extracorporeal photochemotherapy: pemphigus vulgaris--preliminary report

Extracorporeal photochemotherapy is a new form of immunotherapy which involves the extracorporeal photoinactivation of peripheral blood cells by 8-methoxypsoralen in the presence of ultraviolet A irradiation, followed by readministration of the cells. To explore the efficacy of this therapy in the treatment of autoimmune disease, four patients with a lengthy history of corticosteroid and immunosuppressive drug-resistant pemphigus vulgaris were initiated on extracorporeal photochemotherapy. Three patients experienced a complete remission in cutaneous disease expression, permitting discontinuation of medications in two and a substantial decrease in the third. Significant reductions in serum antiepidermal cell antibody titers occurred in all four patients. The treatments were well tolerated without the occurrence of adverse events. These results in a small number of patients suggest that extracorporeal photochemotherapy may prove to be a useful tool in the treatment of aggressive autoimmune disease.     

自体骨髓干细胞移植治疗失代偿期肝硬化的临床效果分析

目的:观察自体骨髓间充质干细胞(BMSC)移植治疗合并不同并发症的失代偿期肝硬化的临床效果。方法:回顾性分析我院自2008年12月至2013年12月收治的148例经自体BMSC移植治疗的肝硬化合并肝性脑病、肝肾综合征、肝源性糖尿病以及消化道出血患者治疗前后的肝、肾功能、血清蛋白、血常规等指标的变化情况。结果:治疗后,肝硬化合并肝性脑病患者的ALT、血氨水平改善明显,TBIL反复;合并肝肾综合征的患者HB、Crea水平改善明显,ALT、AST、DBIL反复;合并肝源性糖尿病患者的ALT、TBIL、DBIL、TB、ALB、血糖水平改善明显;合并消化道出血患者的ALT、TP、ALB改善明显,AST、TBIL、PLT反复。结论:自体BMSC移植治疗肝硬化合并肝源性糖尿病的效果较好,对合并肝性脑病、肝肾综合征以及消化道出血患者的效果欠佳。