Two pathways of exocytosis of cytoplasmic granule contents and target cell killing by cytokine-induced CD3+ CD56+ killer cells

Cytokine-induced killer (CIK) cells are non-major histocompatibility complex-restricted cytotoxic cells generated by incubation of peripheral blood lymphocytes with anti-CD3 monoclonal antibody (MoAb), interleukin-2 (IL-2), IL-1, and interferon-gamma. Cells with the greatest effector function in CIK cultures coexpress CD3 and CD56 surface molecules. CIK cell cytotoxicity can be blocked by MoAbs directed against the cell surface protein leukocyte function associated antigen-1 but not by anti-CD3 MoAbs. CIK cells undergo release of cytoplasmic cytotoxic granule contents to the extracellular space upon stimulation with anti-CD3 MoAbs or susceptible target cells. Maximal granule release was observed from the CD3+ CD56+ subset of effector cells. The cytoplasmic granule contents are lytic to target cells. Treatment of the effector cells with a cell-permeable analog of cyclic adenosine monophosphate (cAMP) inhibited anti-CD3 MoAb and target cell- induced degranulation and cytotoxicity of CIK cells. The immunosuppressive drugs cyclosporin (CsA) and FK506 inhibited anti-CD3- mediated degranulation, but did not affect cytotoxicity of CIK cells against tumor target cells. In addition, degranulation induced by target cells was unaffected by CsA and FK506. Our results indicate that two mechanisms of cytoplasmic granule release are operative in the CD3+ CD56+ killer cells; however, cytotoxicity proceeds through a cAMP- sensitive, CsA- and FK506-insensitive pathway triggered by yet-to-be- identified target cell surface molecules.     

Interval between insulin injection and breakfast in diabetes

The relationship between the insulin-breakfast interval, postprandial increase in blood glucose, and glycaemic control was studied in 58 children with diabetes. Patients recorded insulin-breakfast intervals in a home diary over a seven day period, and during a 24 hour period at the weekend provided eight serial capillary dried blood spots for glucose analysis. The highest mean blood glucose value occurred two hours after breakfast and showed a significant correlation with fructosamine concentrations. Weekend insulin-breakfast intervals ranged from 2-30 minutes, with 70% reporting intervals of less than 15 minutes. There was a significant correlation between the weekend insulin-breakfast interval and the after breakfast increase in blood glucose with a mean increment of 0.4 mmol/l in the 30 minute group and 7.2 mmol/l in the 2 minute group. Over the whole study period, children with mean insulin-breakfast intervals of two to 12 minutes had a mean fructosamine concentration of 376 mumol/l compared with 341 mumol/l in those with intervals of 15-35 minutes. This study has shown that the interval between insulin injection and breakfast significantly influences the morning postprandial rise in blood glucose and consequently short term glycaemic control. It is therefore important that patients are encouraged to leave an interval of about 30 minutes between insulin injection and breakfast.     

The generation of active forms of oxygen by the blood leukocytes, lipid peroxidation and antiperoxide protection in bronchial asthma patients]

A study was made of the generation of active forms of oxygen by leukocytes, of free radical lipid peroxidation and antiperoxide activity (APA) in 52 bronchial asthma (BA) patients depending on the disease phase and of a possibility of their correction with antioxidants. In BA exacerbation, chemiluminescence of leukocytes (CL) and plasma content of malonic dialdehyde (MDA) increase whereas plasma APA reduces as compared to the control. During remission, CL and plasma content of MDA decrease but do not reach normal. Simultaneously one can see a tendency toward plasma APA reduction as compared with the phase of exacerbation. BA patients who received antioxidants in addition to the conventional therapy demonstrated a more pronounced lowering of CL and plasma MDA content than those given the conventional therapy alone. The data obtained attest to the activation of free radical oxygen and lipid processes and to inhibition of plasma APA in BA, providing evidence in favour of including antioxidants in combined therapy of BA.     

Diagnosis and treatment of obstructive sleep apnea in internal medicine

130 inpatients (94 males and 36 females, mean age 51.8 +/- 9.1 years) with suspected obstructive sleep apnoa (OSA) were examined clinically, were questioned and underwent night cardiorespiratory monitoring. A definite OSA diagnosis was made in 83 patients. Sleep continuous positive airway pressure (CPAP) was applied in 40 patients who had moderate and severe sleep respiratory impairment. The treatment was effective in 31(77%) patients who stopped snoring, improved sleep quality and daytime sleepiness. In half of the hypertensive patients elimination of apnoa lowered blood pressure without drugs in day hours. Patients with chronic respiratory insufficiency improved gas exchange. In pulmonary hypertension CPAP therapy reduced pressure in the pulmonary artery. It is concluded that diagnosis and effective individual therapy of most CPAP patients can be provided in therapeutic hospital departments.     

Socio-demographic factors and self-reported funtional status: the significance of social support

Background  

The aim of the present work was to investigate the relative importance of socio-demographic and physical health status factors for subjective functioning, as well as to examine the role of social support.