Disseminating tumor cells and their interactions with leukocytes visualized in the brain.

Brain tumors are increasingly prevalent. Recent advances focus attention on individual, disseminated tumor cells that cannot be imaged or eliminated. Cells of the immune system may be ideally suited to attack individual tumor cells, but more basic understanding is needed. We describe a rat model, using the lacZ reporter gene, that allows identification of individual tumor cells, and tumor-leukocyte interactions in vivo. The model demonstrates how widely tumor can disseminate, without secondary tumorigenesis or recruitment of nonneoplastic cells. It demonstrates that leukocytes have access to disseminating tumor. Among its many applications, this work lays a foundation for developing cell-mediated immunotherapy against individual brain tumor cells.     

Controlled study of meso-2,3-dimercaptosuccinic acid for the management of childhood lead intoxication.

We examined the efficacy and safety of meso-2,3-dimercaptosuccinic acid (DMSA) in children with markedly elevated blood lead (BPb) concentrations. Among 19 children with BPb concentrations of 50 to 69 micrograms/dl (2.41 to 3.33 mumol/L) who received a 5-day inpatient oral course of DMSA (1050 mg/m2 per day), the mean BPb concentration decreased by 61%; in four who received calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA) (1000 mg/m2 per day intravenously), it decreased by 45% (p less than 0.0007). Urinary lead excretion was comparable in both groups. Treatment with DMSA was more effective than treatment with CaNa2EDTA in restoring metabolic activity to the heme pathway and was well tolerated even among nine patients who received concomitant iron supplementation and two who had homozygous deficiency of glucose-6-phosphate dehydrogenase. On discharge, these 19 children received either no chelation therapy or DMSA, 350 or 700 mg/m2 per day for 14 days on an outpatient basis. After 14 days the mean BPb values for the no-chelation, low-DMSA, and high-DMSA groups were 73%, 66%, and 50% of the pretreatment values, respectively. We conclude that a 5-day oral course of DMSA is effective in the treatment of children with severe lead poisoning. In addition, on an outpatient basis the administration of DMSA, 700 mg/m2 per day, is capable of delaying the typical rebound in BPb values and should ultimately reduce the need for repeated hospitalizations.     

Effect of plasmapheresis with substitution by dextran solutions on hemostatic parameters in patients with ischemic heart disease]

Plasmapheresis on a continuous blood flow fractionator to remove 1,200-2,000 ml plasma and substitute for the same values of dextran solutions was employed in the multi-modality treatment of 25 patients with Functional Classes II-IV exertional angina and myocardial infarction. Plasma and thrombocyte hemostatic parameters were examined just before and 24 and 48 hours after plasmapheresis. The analysis of the baseline data revealed that hemostatic changes were directly related to the severity of a disease in the patients and there was a correlation between the increased platelet aggregability and the elevated levels of fibrin-monomeric complexes. Plasmapheresis along with substitution of removed plasma for dextran solutions was accompanied by a profound hypocoagulative effect, as evidenced by plasma and thrombocyte hemostatic parameters. In addition, in patients with baseline high values of platelet aggregability plasmapheresis resulted in its decrease, whereas in those with baseline low values, it led to its increase.     

Neural network based tracking control of a flexible macro-micro manipulator system.

In this paper, we address the problem of stable tracking control of a flexible macro-micro manipulator (M(3)) system. A two-layer neural network is utilized to approximate the nonlinear robot dynamic behavior of the M(3) system, and the controllers for the macro and micro arms are developed without any need for prior knowledge of the dynamic model of the controlled M(3) system. A learning algorithm for the neural network using Lyapunov stability theory is derived. It is shown that both the tracking error and the weight-tuning error are uniformly ultimately bounded under this new control scheme. Simulation results are presented and compared to those obtained using a PD controller.     

Effect of adaptation to continuous stress on the contractile function and electric stability of the heart

In the time course of 15-day stress of moderate intensity, rat experiments indicated that following a day there developed a complex of changes typical of acute stressor syndrome. Five days of post-stress , the stress-related cardiac syndrome ceased, bradycardia developed, the contractile function was limited, and the fibrillation threshold returned to the control values, which was shown to be associated with activation of the cholinergic stress-limiting system. Fifteen days later there was normalization of heart rate and cardiac contractility, the fibrillation threshold remained at the baseline level.     

High survial rate of hamsters given intratracheal instillations of benzo[a]pyrene and ferric oxide and kept on a high {beta}-carotene diet

The study described in this paper was primarily conducted toidentify the cell types involved in the formation, progressionand regression of metaplastic changes in the respiratory tractepithelium of hamsters after intratracheal intubations withbenzo[a]pyrene Furthermore, the role of vitamin A and ß;-carotenein these processes was studied. In the course of the study aremarkable effect of dietary ß;-carotene on survivalof hamsters became a subject of investigation. Hamsters werefed diets with various levels of vitamin A or ß-caroteneand were treated intratracheally with a suspension of benzo[a]pyrenewith ferric oxide in saline. The tumour response of the respiratorytract was very low (2.8%) and hyper- and metaplasia of respiratoryepithelium were virtually absent. However, an interesting observationwas an exceptionally low mortality of only 2% after 69 weeksin the group of hamsters fed a high ß-carotene diet(1% w/w), whereas in the other groups mortality after 69 weeksamounted to 25%. Although the exact cause of death of most ofthe hamsters could not be established, a 40% reduction of lipidperoxidation in the livers was found in the high ß-carotenegroup. Moreover, In this group the degree and incidence of nephroslsand of focal mineralization of kidneys and heart were lowerthan in the other groups. These favourable effects of the highß-carotene diet may have contributed to the unusuallyhigh survival rate in hamsters fed this diet. Further studiesare planned to verify and study this observation.     

Use of dimephosphon in pathogenetic therapy of experimental tuberculosis]

The results of a study of a new synthetic drug dimephosphon used as a pathogenetic means in the treatment of experimental tuberculosis are presented. Dimephosphon was found to be responsible for both the in vivo and in vitro decrease of the degree of MBT resistance to rifampicin. The findings of macroscopic, histologic and bacteriologic examinations demonstrated a significant increase in the effectiveness of antituberculous therapy. Dimephosphon monotherapy in mice elicited manifested stimulation of peritoneal macrophages: increase in O2- production, and decline in extracellular 5-nucleotidase activity. Nemolysine-synthetic cellular splenic activity in mice rose essentially. No direct stimulating influence of dimephosphon on functional macrophage activity in vitro was found.     

Expression of alpha-melanocyte stimulating hormone and the invasive ability of the B16 murine melanoma.

The expression of alpha melanocyte stimulating hormone (MSH) has been investigated in two variants of the B16 murine melanoma. The presence of MSH was demonstrated by immunohistochemical methods using anti-MSH antibodies. The low metastasis variant B16-F1, which grows as an encapsulated non-invasive tumour, showed no alpha-MSH immunoreactivity. In contrast, the high metastasis variant BL6 was found to be alpha-MSH positive and the immunoreactivity was found predominantly in the peripheral invading zones of the tumour.     

Na,K-Atpase in renal tissue of rats in the dynamics of experimental nephritis]

The authors undertook comparative study of the Na, K-ATPase activity in the red cells, ghost corpuscles, and in the cortex and medulla of kidneys of rats with experimental glomerulonephritis (GN) induced by injection of nephrotoxic serum (NTS), during an acute course of the process (1 and 2 weeks after NTS injection) and in chronic affection of the kidneys (10 weeks after NTS injection). The activity of the enzyme both in the red cells and in the ghost corpuscles was reduced significantly, by 28 and 22%, respectively, in the acute period of the disease (one week after NTS injection) but was restored to normal values in the period of chronic affection of the kidneys. The activity of the enzyme did not change in the cortex during the whole period of the study, but in the medulla it diminished in the acute period of the disease and remained reduced (by 27% on the average) during the chronic phase. It is concluded that reduction of the enzyme activity in the studied objects was not caused by the presence of endogenous inhibitors of the enzyme. It is suggested that reduction of Na, K-ATPase activity in the renal medulla may be one of the factors of increase of Na and water excretion in the urine in the chronic phase of GN.