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  • apoptosis  (3)
  • Children's Coma Scale  (1)
  • 1
    ISSN: 1433-0350
    Keywords: Children's Coma Scale ; Demography ; Post-traumatic seizure ; Subdural hematoma ; Intracranial pressure ; Brain-stem reflex ; Outcome predictor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Head injuries in children under the age of 3 years have not been extensively studied, due in part to the lack of an objective tool for neurological assessment. We have developed a Children's Coma Scale (CCS) by modifying the verbal response subscore of the Glasgow Coma Scale (GCS) to overcome this limitation. When applied prospectively to children under 3 years of age, we found the CCS to be useful in predicting outcome. During the 5-year study period from 1981 to 1985, there were 738 patients with head injuries (0–16 years) admitted to the Children's Memorial Hospital in Chicago, including 318 (43.1%) less than 3 years of age. Initial data demonstrated the following observations. The most common mechanism of injury was a fall (75.5%). Although a brief loss of consciousness (LOC) was reported in three-fourths of the patients, prolonged LOC of more than 6 h was uncommon (16/318, 5.0%). The classically described “lucid interval” was seen in only 7 children (2.2%) and was not a reliable indicator of epidural hematoma. Post-traumatic seizures developed more commonly in children under 2 years of age (15.7%) than in older children (11.6% under 3 years of age, 9.6%, entire group), (P〈0.001). Oculovestibular reflex and bilateral fixed dilated pupils had the most reliable correlation with outcome. Other brain-stem reflexes were less useful. Intracranial pressure greater than 40 torr in children with CCS scores of 3, 4 or 5 was inevitably fatal; however, 10 of 16 children with ICP less than 40 torr showed a good outcome.
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  • 2
    ISSN: 1573-4919
    Keywords: antisense oligonucleotide ; apoptosis ; cAMP-dependent protein kinase ; cancer cells ; growth inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The enhanced expression of the RIα subunit of cyclic AMP-dependent protein kinase type 1 (PKA-I) has been correlated with cancer cell growth. We have investigated the effects of sequence-specific inhibition of RIα gene expression on the growth of MCF-7 human breast cancer cells. We report that RIα antisense treatment results in a reduction in RIα expression at both mRNA and protein levels and inhibition of cell growth. The growth inhibition was accompanied by changes in cell morphology, cleavage of poly(ADP-ribose) polymerase (PARP) and appearance of apoptotic nuclei. In addition, bcl-2 protein level was reduced and p53 expression increased in growth arrested cells. Interestingly, RIα antisense inhibited cell viability and induced apoptosis in the absence of p53, suggesting that these actions of RIα antisense are exerted independent of p53. In contrast, two- and four-base mismatched control oligonucleotides had no effect on either cell growth or morphology. These results demonstrate that the RIα antisense, which efficiently depletes the growth stimulatory molecule RIα, induces cell differentiation and apoptosis, providing a new approach to combat breast cancer cell growth.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-4919
    Keywords: retinoic acid ; RARβ ; protein kinase A ; apoptosis ; caspase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Both cAMP and retinoids play a role in cell differentiation and the control of cell growth. A site-selective cAMP analog, 8-Cl-cAMP and retinoic acid synergistically inhibit growth and induce apoptosis in certain cancer cells. In advanced or recurrent malignant diseases, retinoic acid (RA) is not effective even at doses that are toxic to the host. The objective of our present study was to examine the mechanism(s) of synergistic effects of retinoic acid (9-cis, 13-cis or all-trans RA) and 8-Cl-cAMP on apoptosis in human ovarian cancer NIH: OVCAR-3 and OVCAR-8 cells. RA induced growth inhibition and apoptosis in OVCAR-3 and OVCAR-8 cells. 8-Cl-cAMP acted synergistically with RA in inducing and activating retinoic acid receptor β (RARβ) which correlates with growth inhibition and apoptosis in both cell types. In addition, induction of apoptosis by RA plus 8-Cl-cAMP requires caspase-3 activation followed by cleavage of anti-poly(ADP-ribose) polymerase. Furthermore, mutations in CRE-related motif within the RARβ promoter resulted in loss of both transcriptional activation of RARβ and synergy between RA and 8-Cl-cAMP. RARβ expression appears to be associated with induction of apoptosis. Introduction of the RARβ gene into OVCAR-3 cells resulted in gain of RA sensitivity. Loss of RARβ expression, therefore, may contribute to the tumorigenicity of human ovarian cancer cells. Thus, combined treatment with RA and 8-Cl-cAMP may provide an effective means for inducing RARβ expression leading to apoptosis in ovarian cancer cells.
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  • 4
    ISSN: 1573-7217
    Keywords: antisense ; protein kinase A ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In recent years, several laboratories have explored the possibility of using antisense oligodeoxynucleotides for specific manipulation of gene expression leading to cancer treatment. The enhanced expression of the RIα subunit of cyclic AMP-dependent protein kinase type I (PKA-I) has been correlated with cancer cell growth. In the present study, the effects of an antisense oligodeoxynucleotide targeted against RIα subunit of PKA-I on growth inhibition and apoptosis in MDA-MB-231 human breast cancer cells were investigated. The growth inhibitory effects of RIα antisense oligodeoxynucleotide correlated with a decrease in the RIα mRNA and protein levels. The growth inhibition was accompanied by changes in the cell cycle phase distribution, cell morpbology, cleavage of poly (ADP-ribose) polymerase (PARP), and appearance of apoptotic nuclei. By comparison, mismatched control oligodeoxynucleotide had no effect. On the basis of these results, it can be suggested that the RIα antisense oligodeoxynucleotide, which efficiently depletes the growth stimulatory RIα and induces apoptosis/differentiation, could be used as a therapeutic agent for breast cancer treatment.
    Type of Medium: Electronic Resource
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