Pediatric central nervous system tumors

Numerous collagenous structures must be reconstituted following injury to the skin in order to return function to this tissue. The basement membrane zone, vascular basement membranes, and the dense connective tissue of the dermis are examples of structures that contain a number of different collagen types and that may need replacement following injury. In addition, a scar is deposited at the site of damage in order to substitute for elements lost in the trauma and for elements that cannot be successfully replaced. Clearly, cells resident within the different compartments of the skin are able to synthesize and deposit collagen to reform these multiple structures. However, accumulating experimental evidence suggests that in addition to these resident cells, blood-borne cells may be responsible for the deposition of a portion of the newly synthesized collagen. Studies from this laboratory point to the activated monocyte as a potential source of collagen in the wound environment. Given the dynamics of the process, the hypothesis is proposed that during normal wound healing, the activated monocyte is a source of collagen essential for the rapid formation of a provisional matrix conducive for the subsequent formation of granulation tissue. Collagen synthesis also occurs by expanded populations of resident cells, under the influence of inflammatory cell-derived mediators, which results in the major accumulation of collagen during normal wound repair. However, if a chronic inflammatory state is initiated, the activated monocytes may remain in sufficient numbers to deposit collagen leading to a pathological lesion.     

Genetics of pediatric central nervous system tumors

PURPOSE: Pediatric central nervous system (CNS) tumors comprise a wide variety of histologic subtypes ranging from the benign juvenile pilocytic astrocytoma to the highly aggressive atypical teratoid/rhabdoid tumor. Although some brain tumors are seen in association with inherited genetic disorders which predispose to malignancies, most are sporadic. Current knowledge regarding the cytogenetic and molecular genetic events which have been implicated in the development or progression of common brain tumors in children in the subject of this review. METHODS: Combined cytogenetic and molecular genetic approaches, including fluorescence in situ hybridization, have been used to identify genomic alterations in different histologic types of pediatric brain tumors. RESULTS: The most frequent abnormality in primitive neuroectodermal tumor/medulloblastoma is an i(17q), present in approximately 50% of cases. This finding implicates the presence of a tumor suppressor gene on 17p, which is important in tumor development. A number of genes on 17p have been eliminated as candidates for this locus, including TP53. A tumor suppressor gene in chromosome band 22q11.2 has been hypothesized to play a role in atypical teratoid/rhabdoid tumors, and positional cloning strategies are in progress to identify a rhabdoid tumor gene. Chromosome 22 deletions are also seen in meningiomas and a small percentage of ependymomas, but it is not yet known whether the same gene is responsible for more than one malignancy. With regard to childhood astrocytomas, tumor-associated genetic changes have not yet been identified for the common juvenile pilocytic or low grade diffuse astrocytoma. In contrast, malignant anaplastic astrocytomas and glioblastoma multiforme have abnormalities similar to those seen in adults, including loss of alleles on 17p13 and TP53 mutations, trisomy 7, EGFR rearrangements, and loss of chromosomes 10 and 22. CONCLUSIONS: The presence of tumor-associated genetic abnormalities has clinical utility in a differential diagnostic setting, and has lead to the identification of genes which contribute to tumorigenesis.     

Dialysis therapy and central nervous system disturbances

Complications connected with chronic dialysis therapy and manifesting themselves as symptoms of central nervous system lesion, are presented. A special attention was paid to dialysis encephalopathy, to dialysis disequilibrium syndrome and to the vascular lesion of brain, that of the dialysis.     

Cytogenetic analysis of 109 pediatric central nervous system tumors

Reports of cytogenetic abnormalities in pediatric central nervous system (CNS) tumors are important for collection and comparison of large numbers of karyotypes of primary CNS neoplasms to produce statistically significant correlations. We report cytogenetic results of 119 samples of pediatric CNS tumors from 109 patients. Tumors included 33 low-grade astrocytomas, 18 high-grade astrocytomas, 14 gangliogliomas, 13 ependymomas, 17 primitive neuroectodermal tumors (PNET), three choroid plexus papillomas and carcinomas, and a miscellaneous group of 20 rare primary CNS tumors and metastases. In each group, cytogenetic results were correlated with histologic subtype and survival. The study indicated specific chromosome abnormalities in different groups of tumors. Low-grade astrocytomas showed mostly numeric abnormalities with gains of chromosome 7, high-grade astrocytomas showed differences from karyotypic changes observed in adults in lacking double minutes (dmin) and monosomy 10. The ependymoma group showed the largest proportion of abnormal karyotypes with frequent involvement of chromosome 6 and 16. Chromosome 6 was the single most common abnormal chromosome in this study, closely followed by chromosomes 1 and 11. Pediatric CNS neoplasms differ from adult tumors cytogenetically as well as histologically and biologically.     

Recent advances in the biology of central nervous system tumors

BACKGROUND: In order to study the biosynthesis of vitamin B12, it is necessary to produce various intermediates along the biosynthetic pathway by enzymic methods. Recently, information on the organisation of the biosynthetic pathway has permitted the selection of the set of enzymes needed to biosynthesise any specific identified intermediate. The aim of the present work was to use recombinant enzymes in reconstituted multi-enzyme systems to biosynthesise particular intermediates. RESULTS: The products of the cobG and cobJ genes from Pseudomonas denitrificans were expressed heterologously in Escherichia coli to afford good levels of activity of the corresponding enzymes, CobG and CobJ. Aerobic incubation of precorrin-3A with the CobG enzyme alone yielded precorrin-3B. When CobJ and S-adenosyl-L-methionine were included in the incubation, the product was precorrin-4. Both precorrin 3B and precorrin-4 are known precursors of vitamin B12 and their availability has allowed new mechanistic studies of enzymic transformations. CONCLUSIONS: Our results show that the expression of the CobG and CobJ enzymes has been successful, thus facilitating the biosynthesis of two precursors of vitamin B12. This lays the foundation for the structure determination of CobG and CobJ as well as future enzymic experiments focusing on later steps of vitamin B12 biosynthesis.     

Primary central nervous system tumors: advances in knowledge and treatment

The ability to diagnose, monitor, and treat CNS tumors has been improved by new imaging techniques such as positron emission tomography (PET) scanning and functional MR imaging, stereotactic surgery, delivery of radiotherapy with brachytherapy and radiosurgery, and novel methods for delivering chemotherapy. These innovations combined with the new information about tumor pathogenesis and behavior revealed by molecular research give hope that more specific treatments for malignant CNS tumors will be developed in the future.     

Influence of chronic Toxoplasma infection on ethylnitrosourea-induced central nervous system tumors in rats

Because prior work with mice had revealed remarkable inhibition of central nervous system (CNS) tumor by chronic Toxoplasma infection, the effect of immunomodulation produced by this obligate intracellular parasite was studied in rats which developed CNS tumors following transplacental exposure to the chemical carcinogen ethylnitrosourea. Groups of Fischer 344 rats which had been exposed to ethylnitrosourea were either uninfected or infected at 1 month of age with a virulent strain of Toxoplasma gondii. Rats were sacrificed when morbid symptoms from tumor growth developed, and neural tissue was prepared for light microscopy. Chronic Toxoplasma infection had no effect on the survival of rats or on the amount, location, or histological type of CNS tumor which developed. Although serum antibody to Toxoplasma was present in all infected rats for the duration of the experiment, there was no histological evidence in the brain of a cellular response to infection or to the presence of tumor. When these results are compared to prior experiments of CNS tumor in mice, they suggest that mechanisms of protection against Toxoplasma infection differ in mice and rats and that an inflammatory component produced by the Toxoplasma organism in the brain is a necessary prerequisite for tumor inhibition.     

Combined therapy for primary central nervous system lymphoma in immunocompetent patients

A retrospective series of 13 immunocompetent patients with histological diagnosis of primary central nervous system lymphoma (PCNSL) is presented. The series was divided into Group A, 6 patients treated with radiotherapy alone, and Group B, 7 patients treated with chemotherapy and radiotherapy. Clinicopathological patterns were similar for the two groups. In Group A, 4 patients achieved complete remission after radiotherapy (45-59.4 Gy) but relapsed within 9 months and died within 21 months of diagnosis. 4 Group B patients received chemotherapy followed by radiotherapy, and three who received a methotrexate-containing regimen are alive and disease-free at 34, 42 and 45 months, while the fourth died after 11 months. The other 3 subjects in this group were treated with radiotherapy followed by chemotherapy, and died within 15 months of diagnosis. Although radiotherapy is the standard treatment, chemotherapy has potentially an important role in the management of PCNSL. The sequence of combined treatment could be crucial to improvement of outcome.     

Gene transfer to the central nervous system by transplantation of cerebral endothelial cells

I recorded the electric organ discharges (EODs) of 331 immature Brachyhypopomus pinnicaudatus 6-88 mm long. Larvae produced head-positive pulses 1.3 ms long at 7 mm (6 days) and added a second, small head-negative phase at 12 mm. Both phases shortened duration and increased amplitude during growth. Relative to the whole EOD, the negative phase increased duration until 22 mm and amplitude until 37 mm. Fish above 37 mm produced a "symmetric" EOD like that of adult females. I stained cleared fish with Sudan black, or fluorescently labeled serial sections with anti-desmin (electric organ) or anti-myosin (muscle). From day 6 onward, a single electric organ was found at the ventral margin of the hypaxial muscle. Electrocytes were initially cylindrical, overlapping, and stalk-less, but later shortened along the rostrocaudal axis, separated into rows, and formed caudal stalks. This differentiation started in the posterior electric organ in 12-mm fish and was complete in the anterior region of fish with "symmetric" EODs. The lack of a distinct "larval" electric organ in this pulse-type species weakens the hypothesis that all gymnotiforms develop both a temporary (larval) and a permanent (adult) electric organ.     

Age at onset of puberty following high-dose central nervous system radiation therapy

OBJECTIVE: To determine if a relationship exists between age at irradiation, sex of the patient, and age at onset of puberty and pubarche in children treated with high-dose radiation to the central nervous system. DESIGN: Case series. SETTING: Tertiary care institutional practices and clinics. PATIENTS: Thirty-six children treated with high-dose irradiation (hypothalamic pituitary dose, 30-72 Gy) by conventional (n = 29) or hyperfractionated (n = 7) schedules. Girls were treated before age 8 years and boys before age 9 years. Twenty-six of the 36 children also received chemotherapy. All tumors were distant from the hypothalamic-pituitary region. MAIN OUTCOME MEASURE: Age at onset of puberty and pubarche. RESULTS: In girls, the median age at onset of puberty was 9.3 years vs 10.9 years for controls (P < .01); pubarche occurred at 9.4 years vs 11.2 years for controls (P < .01). In boys, the median age at onset of puberty--genital II--was 11.0 years vs 11.5 years for controls (P = .30); pubarche occurred at a median age of 10.5 years vs 12 years for controls (P = .25). A censored-data normal linear regression model was used to account for children (n = 6) who had not reached puberty. Age at diagnosis (P < .01) and sex (P = .01) were significant predictors of age at onset of puberty. Body mass index SD score (z score) was inversely related to age at onset of puberty (r = -0.77) and was greater at onset of puberty in girls than in boys. CONCLUSION: In children who have received high-dose cranial radiation therapy, a significant positive correlation exists between age at diagnosis and age at onset of puberty in boys and girls.     

Remyelination of the central nervous system

The three typical stages in the clinical course of multiple sclerosis (relapse, persistent disability and progression) can be explained on the basis of inflammation, demyelination and failure of repair leading to axon degeneration and astrocytosis. Strategies are being evaluated for limiting the inflammatory process using immunological treatments and these may have unexpected dividends in promoting endogenous remyelination. Increasing knowledge on glial lineages and axon-glial interactions needed for stable myelination also offer the prospect for enhancing remyelination through growth factor therapy and cell implantation.     

Tumors of the central nervous system

Neoplasia of the central nervous system (CNS) can be divided into two main categories: nonpituitary CNS neoplasia and pituitary adenomas. Nonpituitary CNS neoplasias are generally compressive in nature, although some are also invasive. The majority of reported CNS tumors are secondary with only a few originating from nervous tissue. Pituitary adenomas predominantly occur in the pars intermedia of the older horse. Clinical signs, diagnostic testing, and possible treatments are discussed.     

Mutation analysis and loss of heterozygosity of PEDF in central nervous system primitive neuroectodermal tumors

CF mice, i.e., mice without functional CFTR (cystic fibrosis transmembrane conductance regulator) exhibit a very low basal Isc in all regions of the intestinal tract. The low basal Isc in the intestinal epithelia of the CF mice appears to be a result of lack of spontaneous Cl- secretion (and possibly HCO3- secretion) mediated by neurotransmitter release from the enteric nervous system. In contrast to intestinal epithelia from normal mice, the intestinal epithelia of CF mice do not secrete Cl- in response to agents that increase cAMP (forskolin). Furthermore, as in human CF patients, agents that increase intracellular Ca2+ (bethanacol, ionomycin) failed to elicit Cl- secretion in the intestinal epithelia of CF mice. There was no difference in the electrogenic Na(+)-coupled glucose absorption in the CF murine jejuna compared to jejuna from normal mice. However, further studies are warranted to determine whether amiloride-sensitive Na+ absorption is upregulated in the murine CF colon. It was concluded that the intestinal epithelium of the CF mouse model exhibits some striking similarities to its human counterpart, and therefore should be very useful in further characterizing the ion transport defects in this disease.     

Uveitis and central nervous system vasculitis

The purpose of this double-blind study was to investigate the influence of adding a quercetin-containing supplement to the diet on plasma quercetin status, serum/platelet fatty acid levels and risk factors for heart disease. Healthy men and women with cholesterol levels of 4.0-7.2 mmol/L, consumed four capsules daily of either a quercetin-containing supplement (1.0 g quercetin/d) or rice flour placebo for 28 d. Quercetin intakes were approximately 50-fold greater than the dietary intakes associated with lower coronary heart disease mortality on the basis of epidemiologic studies. Subjects consuming quercetin-containing capsules had plasma quercetin concentrations approximately 23-fold higher than those of subjects consuming the control capsules. Quercetin supplementation did not modify serum total, LDL or HDL cholesterol or triglyceride levels. There were also no alterations of other cardiovascular disease or thrombogenic risk factors, including platelet aggregation, platelet thromboxane B2 production, blood pressure or resting heart rate. Furthermore, there was no effect on the levels of (n-6) or (n-3) polyunsaturated fatty acids in serum or platelet phospholipids. In conclusion, supplementation with quercetin-containing capsules markedly enhanced the plasma quercetin concentration but had no effect on other cardiovascular or thrombogenic risk factors.     

Cyclooxygenases and the central nervous system

Prostaglandins (PGs) were first described in the brain by Samuelsson over 30 years ago (Samuelsson, 1964). Since then a large number of studies have shown that PGs are formed in regions of the brain and spinal cord in response to a variety of stimuli. The recent identification of two forms of cyclooxygenase (COX; Kujubu et al., 1991; Xie et al., 1991; Smith and DeWitt, 1996), both of which are expressed in the brain, along with superior tools for mapping COX distribution, has spurred a resurgence of interest in the role of PGs in the central nervous system (CNS). In this review we will describe new data in this area, focusing on the distribution and potential role of the COX isoforms in brain function and disease.     

Phaeochromocytoma with central nervous system manifestations

A 35-year-old Samoan male presented with intermittent headaches and hypertensive episodes for several months. A subsequent left adrenal gland phaeochromocytoma was discovered and surgically excised. An MRI of his brain demonstrated periventricular, basal ganglia, and centrum semi-ovale infarction. We suggest that catecholamine excess and neuropeptide Y may contribute to intracerebral haemorrhage and infarcts associated with phaeochromocytomas. Additionally, our surgical approach in removing the phaeochromocytoma is discussed.