Computed tomographic (CT) demonstration of calcification of the ligamenta flava of the lumbosacral spine associated with protrusion of the intervertebral disc

Axial computed tomographic (CT) scan of the lumbosacral region was performed in 220 patients. The patient population was divided into three groups. The control group included 40 elderly patients without calcification of the ligamenta flava. The second group included 150 patients with posterior protrusion of the intervertebral discs. The third group included 30 patients with spinal stenosis. More than 80% of the patients of the second and the third group had calcification of the ligamenta flava. The diagnostic and practical importance of these findings is discussed.     

MRI demonstration and CT correlation of the brain in patients with idiopathic intracerebral calcification

Twenty-two patients aged 36–63 years were diagnosed as having Fahr's syndrome on the basis of the presence on CT of unexpected extensive calcification of the basal ganglia. Even when associated with calcification of other brain areas, the main diagnostic criterion remained basal ganglia calcification larger than 800 mm². Normal values of parathormone, serum calcium and phosphorus excluded hypercalcaemia and hypoparathyroidism. Mitochondrial CNS disease was excluded clinically. MRI and repeated CT and neurological examination were performed in all of the patients. The patients were divided into two groups: neurologically asymptomatic (group 1) and neurologically symptomatic (group 2). T2-weighted sequences demonstrated hyperintense areas in all of the patients involving the white and the grey matter of the brain. In group 1 the hyperintense lesions were significantly smaller than in group 2. The neurological symptoms correlated better with the hyperintensities on T2-weighted MR images than with the calcification demonstrated on CT. Hyperintensities in T2-weighted MRI and the areas shown by CT to have calcification had different locations. In 15 patients with dementia, the white matter of the entire centrum semiovale was bilaterally hyperintense. In another 3 patients with hemiparesis, hyperintense areas in the internal capsule, contralateral to the side of hemiparesis, were demonstrated in the T2-weighted sequence. The hyperintense T2 signals may reflect a slowly progressive, metabolic or inflammatory process in the brain which subsequently calcifies and are probably responsible for the neurological deficit observed.     

Epilepsy in patients with brain metastases triggered by intravenous contrast medium

187 patients with histologically proven primary neoplasms underwent computed tomography (CT) of the brain following intravenous administration of contrast medium. Eight developed focal epileptic seizures 2 to 4 minutes after the start of the injection. In three of these patients, in whom there was CT evidence of bilateral mass lesions of the brain, this epileptic activity became generalised into grand mal seizures, and two died in status epilepticus. In the other five patients with unilateral deposits in the brain, the focal fits corresponded to the site of the lesion shown by CT. Three of the patients had follow-up electroencephalography (EEG) examinations which showed unilateral focal activity, and their EEG foci correlated with the CT findings.     

Influence of adoptively transferred thioglycollate-elicited peritoneal macrophages on metastasis formation in mice with depressed or stimulated NK activity

The effect of thioglycollate-elicited macrophages (TG-M) on natural killer (NK)-cell activity and metastases formation in mice was investigated. Intravenously (i.v.) inoculated TG-M inhibited spleen NK activity of normal mice and abrogated polyinosinic: polycytidylic (poly IC) induced augmentation of NK cell function. TG-M also inhibited the clearance of i.v.-injected radiolabeled B16 melanoma cells from the lungs of normal or poly IC stimulated mice. Formation of experimental B16 melanoma metastases was dramatically increased in mice pretreated with TG-M. Administration of TG-M increased metatasis formation to a greater extent than anti-asialo GM₁ serum, while anti-asGM₁ serum was more efficient than TG-M in depressing spleen NK cell activity. When mice with low NK reactivity (beige mice or mice treated with anti-asialo GM₁ serum) were inoculated with TG-M, there was a substantial additive augmenting effect on metastasis formation in the lungs. Treatment with poly IC elevated NK-cell activity and had profound antimetastatic effects in normal but not in TG-M pretreated mice. The metastasis augmenting effect of TG-M was fully expressed in poly IC-treated mice as well as in athymic nude mice. Inoculation of proteose peptone-elicited macrophages (PM), unlike TG-M, did not depress NK activity or augment metastasis formation in normal or poly IC-treated mice. However, since the inhibition of NK activity in TG-M-treated mice was relatively weak, and a substantial additional increase in metastases was observed in NK-depressed mice after transfusion of TG-M, it seems unlikely that the TG-M-induced inhibition of NK reactivity is entirely responsible for the augmented formation of metastases. Further studies revealed that i.v. inoculation of TG-M, but not PM, induced intravascular inflammatory reactions, and damage to endothelial cells and basement membrane of the lung vasculature. These reactions may contribute to increased tumor cell extravasation and metastasis formation in mice pretreated with TG-M.     

Lewis lung carcinoma (3LL) cells treated in vitro with ultraviolet radiation show reduced metastatic ability due to an augmented immunogenicity

The metastatic ability of 3LL tumor following in vitro irradiation with ultraviolet (u.v.) light was studied. Tumor cells were exposed to two courses of u.v.-irradiation (3LL × 2u.v. cells) and after two weeks of culture they were inoculated intravenously (i.v.) into syngeneic mice. These cells produced significantly fewer pulmonary metastases than the untreated population. In addition, intrafootpad (i.f.p.) injections of 3LL × 2u.v. cells into immunocompetent animals induced tumors only in 40 per cent of recipients. Interestingly, in normal mice with progressively growing 3LL × 2u.v. tumors, the formation of spontaneous pulmonary metastases was prevented, whereas metastatic foci were observed in 70 per cent of the nude recipients. The metastatic properties of u.v.-treated tumor cells were further analysed by using individual clones with varying immunogenicity. We found that variants with augmented immunogenicity also showed a parallel decrease in metastatic potential. Studies on H-2 antigen expression in different clones revealed that immunogenic and low metastatic variants expressed levels of H-2 antigens higher than the tumorigenic and metastatic clones. Finally, by using cyclophosphamide (Cy) treatment and adoptive transfer of immune spleen cells we were able to eradicate macroscopic 3LL pulmonary metastasis. These results demonstrate that the decrease of metastatic ability in u.v.-treated cells was mainly due to an increase in their immunogenicity and H-2 antigen expression.     

Multiplexed immunobead-based cytokine profiling for early detection of ovarian cancer.

Early detection of ovarian cancer might improve clinical outcome. Some studies have shown the role of cytokines as a new group of tumor markers for ovarian cancer. We hypothesized that a panel comprised of multiple cytokines, which individually may not show strong correlation with the disease, might provide higher diagnostic power. To evaluate the diagnostic utility of cytokine panel, we used a novel multianalyte LabMAP profiling technology that allows simultaneous measurement of multiple markers. Concentrations of 24 cytokines (cytokines/chemokines, growth, and angiogenic factors) in combination with cancer antigen-125 (CA-125), were measured in sera of 44 patients with early-stage ovarian cancer, 45 healthy women, and 37 patients with benign pelvic tumors. Six markers, i.e., interleukin (IL)-6, IL-8, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), and CA-125, showed significant differences in serum concentrations between ovarian cancer and control groups. Out of this group, IL-6, IL-8, VEGF, EGF, and CA-125, were used in a classification tree analysis that resulted in 84% sensitivity at 95% specificity. The receiver operator characteristic curve created using the combination of markers produced sensitivities between 90% and 100% in the area of 80% to 90% specificity, whereas the receiver operator characteristic curve for CA-125 alone resulted in sensitivities of 70% to 80%. The classification tree analysis for discrimination of benign condition from ovarian cancer used CA-125, granulocyte colony-stimulating factor (G-CSF), IL-6, EGF, and VEGF resulting in 86.5% sensitivity and 93.0% specificity. The presented data show that simultaneous testing of a panel of serum cytokines and CA-125 using LabMAP technology may present a promising approach for ovarian cancer detection.     

Computed tomographic demonstration of calcification of the ligamenta flava of the lumbosacral spine in ankylosing spondylitis.

An axial computed tomographic (CT) scan of the lumbosacral regions was performed in 65 patients. The patient population was divided into two groups. The first (control) group included 40 elderly patients without calcification of the ligamenta flava. The second group included 25 patients with ankylosing spondylitis. More than 90% of those in the second group showed calcified lumbosacral ligamenta flava. In two patients these calcifications produced spinal stenosis. The diagnostic and practical importance of these findings are discussed.     

A single-stranded DNA binding protein binds the origin of replication of the duplex kinetoplast DNA.

Replication of the kinetoplast DNA (kDNA) minicircle of trypanosomatids initiates at a conserved 12-nt sequence, 5'-GGGGTTGGTGTA-3', termed the universal minicircle sequence (UMS). A sequence-specific single-stranded DNA-binding protein from Crithidia fasciculata binds the heavy strand of the 12-mer UMS. Whereas this UMS-binding protein (UMSBP) does not bind a duplex UMS dodecamer, it binds the double-stranded kDNA minicircle as well as a duplex minicircle fragment containing the origin-associated UMS. Binding of the minicircle origin region by the single-stranded DNA binding protein suggested the local unwinding of the DNA double helix at this site. Modification of thymine residues at this site by KMnO4 revealed that the UMS resides within an unwound or otherwise sharply distorted DNA at the minicircle origin region. Computer analysis predicts the sequence-directed curving of the minicircle origin region. Electrophoresis of a minicircle fragment containing the origin region in polyacrylamide gels revealed a significantly lower electrophoretic mobility than expected from its length. The fragment anomalous electrophoretic mobility is displayed only in its native conformation and is dependent on temperature and gel porosity, indicating the local curving of the DNA double helix. We suggest that binding of UMSBP at the minicircle origin of replication is possible through local unwinding of the DNA double helix at the UMS site. It is hypothesized here that this local melting is initiated through the untwisting of unstacked dinucleotide sequences at the bent origin site.