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.     

Isolated Coccygeal Tuberculosis

Isolated tuberculosis of the coccyx is extremely rare. A 35-year-old man presented with a 3-month history of coccygeal and gluteal pain. Computed tomography and magnetic resonance imaging revealed osseous destruction and a large enhancing mass involving the coccyx with anterior and posterior extension. Pathologic examination of the surgical specimen revealed necrosis, chronic granulomatous inflammation, and multinucleated giant cells consistent with tuberculosis. This case highlights the importance of considering tuberculosis as a diagnosis even though unusual sites are involved.     

Early sexual maturation,central adiposity and subsequent overweight in late adolescence. A four-year follow-up of 1605 adolescent Norwegian boys and girls: the Young HUNT study

Background  

Early sexual maturation has been associated with overweight that may persist after the completion of biological growth and development. We have prospectively examined the influence of early sexual maturation on subsequent overweight in late adolescence and assessed if this association was modified by central adiposity in early adolescence.     

Impaired visual memory in rats reared in isolation is reversed by D-cycloserine in the adult rat

Previous studies have shown that environmental factors can influence cholinergic and glutamatergic activity in the developing brain, and that the variations in neurochemistry are accompanied by behavioral changes in later life. Rats reared in isolated, social, or enriched environments were tested with a visual discrimination task in adulthood. The results show that saline-treated rats reared in isolation exhibited impaired retention of the discrimination task compared to rats raised in social or enriched environments. However, systemic administration of the NMDA receptor agonist, D-cycloserine (3 mg/kg), restored normal memory function in cognitively impoverished rats. Acquisition of the task was not affected by the rearing conditions. D-Cycloserine is considered to be an efficient cognitive enhancer probably able to compensate for assumed loss of NMDA receptors during isolated rearing.     

Deteriorating ischaemic stroke. cytokines,soluble cytokine receptors,ferritin, systemic blood pressure,body temperature,blood glucose,diabetes, stroke severity,and CT infarction-volume as predictors of deteriorating ischaemic stroke

The immune reactivity implicated in the pathogenesis of Guillain-Barré syndrome (GBS) and related diseases, which occur following infection with specific strains of Campylobacter jejuni bearing sialylated lipopolysaccharide structures that cross-react with specific gangliosides, is consistent with provocation of inflammation via molecular mimicry. In this review, we have focused upon microbial characteristics and structures, the fine structure of the essential carbohydrate determinants, and the application of our proposed criteria, modified from those of Koch for causation of infectious and of Witebsky for autoimmune diseases, to the circumstance of infectious induction of autoimmune disorder.     

Serum cystatin C as a marker of the renal function in patients with spinal cord injury

OBJECTIVE: To investigate the relationship between serum cystatin C, serum creatinine, and (51)Cr-EDTA-clearance in patients with spinal cord injury. SETTING: The Spinal Cord Unit, Viborg-Kjellerup County Hospital. METHODS: Twenty-four men and seven women aged 20.3 to 68.0 years with motor complete spinal cord injury (ASIA A or B) were included. Serum cystatin C was measured by an automated particle-enhanced nephelometric immunoassay (Dade Behring), serum creatinine by an enzymatic method (Vitros 950), and (51)Cr-EDTA-clearance by a multiple plasma sample method. RESULTS: A linear relationship was found between (51)Cr-EDTA-clearance and the reciprocal values of cystatin C and creatinine. The correlation coefficient between (51)Cr-EDTA-clearance and 1/cystatin C was 0.72 compared to the correlation coefficient between (51)Cr-EDTA-clearance and 1/creatinine being 0.26. Comparison of the area under the curves in the non-parametric receiver operating characteristics (ROC) plots for serum cystatin C (area under the curve (AUC)=0.912; SE=0.065), and serum creatinine (AUC=0.507; SE=0.115) revealed significant differences (P-values=0.0005). CONCLUSION: In patients with spinal cord injury serum cystatin C is a better marker of the renal function compared to serum creatinine.     

Preoperative Staging of Rectal Cancer With MRI: Accuracy and Clinical Usefulness

Background: Preoperative staging is essential for planning of optimal therapy for patients with rectal cancer. Recently, magnetic resonance imaging (MRI) is used frequently because of its benefits of clear pelvic image are better than other diagnostic methods. The purpose of this study was to determine accuracy rates and clinical usefulness of MRI in preoperative staging of rectal cancer.Methods: Between February, 1997, and December, 1999, 217 patients with histologically proven rectal cancer were staged preoperatively and had surgical resections performed. MRI criteria for depth of invasion was determined by the degree of disruption of the rectal wall. Metastatic perirectal lymph nodes were considered to be present if they showed heterogenous texture, irregular margin, and enlargement (.10 mm).Results: The accuracy of the MRI for determining depth of invasion was 176/217 (81%) and regional lymph node invasion was 110/217 (63%). In the T stage, accuracy rate of T1 was 3/4 (75%), T2 was 20/37 (54%), T3 was 141/162 (87%), and T4 was 12/14 (86%), respectively. The specificity of lymph node invasion was 45/110 (41%) and the sensitivity was 91/107 (85%). The accuracy rate of regional lymph node involvement was 136/217 (63%). T1 and T2 were overstaged in 1/4 (25%) and 17/37 (46%), respectively, and T3 was understaged in 15/162 (9.2%). The accuracy rate to detect metastatic lateral pelvic lymph node was 4/14 (29%) after lateral pelvic lymph node dissection was done in 14 patients under MRI. The accuracy rate in assessing levator ani muscle tumor involvement was 8/11 (72%).Conclusions: MRI showed a good, comparable accuracy rate for determining depth of tumor invasion, compared with transrectal ultrasonography, which still has a low accuracy rate for detecting metastatic lymph node. MRI with endorectal coil may increase the accuracy rate of T1 and T2 lesions. In addition, clear sagittal and coronal sectional pelvic images can give a lot of information about adjacent organ invasion or any invasion of levator ani muscle. MRI can be useful for choosing an appropriate extent of lymph node dissection and type of surgery.     

Serum-cortisol reflects severity and mortality in acute stroke

BACKGROUND: The adrenal glucocorticoid stress response in humans causes catabolism, increasing blood glucose and heart rate, and possibly potentiates ischaemic damage to neurons. These effects could induce secondary brain damage in acute stroke. MATERIALS AND METHODS: This prospective study was based on a single determination of s-cortisol in 172 patients included within 24 h of stroke onset, 50% within 12 h of stroke onset. All patients were admitted to hospital within 6 h of stroke onset. We investigated the relations of s-cortisol to neurological deficit measured by Scandinavian Stroke Scale (SSS), lesion volume on CT-scan, blood glucose on admission, pulse rate, blood pressure, body temperature, deteriorating stroke, cytokines and cytokine receptors, and outcome. RESULTS: In a multivariate logistic regression analysis, s-cortisol was independently related to death within 7 days of stroke onset, odds ratio (OR) Cortisol(+100 nmol/l) 1.9 (95% CI 1.01-3.8); serum-cortisol was, however, not a predictor of death or dependency within 3 months. S-cortisol correlated to SSS (rho=-0.45, p<0.001), body temperature (rho=0.27, p<0.001), pulse rate (rho=0.26, p<0.001), and lesion volume (rho=0.33, p<0.001). S-cortisol was related to the presence of insular damage. CONCLUSION: Acute stroke mortality related to increasing serum-cortisol levels. S-cortisol was associated with stroke severity and markers reflecting stroke severity.