Intramedullary pilocytic astrocytomas — a clinical and morphological study after combined surgical and photon or neutron therapy

Ten patients suffering from intramedullary pilocytic astrocytomas (WHO-classification: astrocytoma grade I) were investigated catamnesticly. Combined surgery and radiotherapy was performed. Seven patients received neutron irradiation postoperatively. In four cases the neurological symptoms were improved after follow-up periods ranging from 33 to 89 months. The three other patients died after 6 to 21 months. The autopsy findings of a 14 year old child are presented. Our results are compared with reports in the literature. In addition, long-term problems of the spinal column are discussed. It seems that the combined surgical and neutron therapy improves the prognosis of pencil gliomas.     

The progression of deafferentation as a retrograde reaction to hypoglossal nerve injury

Summary This study examined the fate of axon terminals of one of the major sources of hypoglossal afferents, the spinal V nucleus, after XIIth nerve resection in adult Sprague-Dawley rats. In order to anterogradely label trigemino-hypoglossal projections, small quantities of horse radish peroxidase were pressure-injected into the ipsilateral dorsal (mandibular) portion of the spinal V nucleus two days before the animals were killed. Survival periods ranged from 5 to 33 days after nerve injury (dpo). Axonal injury produced relative changes in the association of labelled axon terminals to structures in the hypoglossal nucleus on the injured side. The proportion of horse radish peroxidase-labelled spinal V nucleus terminals with spherical vesicles (S-terminals) that were unapposed to hypoglossal somata or dendrites increased rapidly and reached maximal levels by 11 dpo. By contrast, the isolation of labelled terminals with pleomorphic/flattened vesicles (P/F-terminals) from postsynaptic structures began later, advanced at a slower rate and did not attain maximal levels until 20 dpo. S-terminals not apposed to neuronal cell parts increased at a rate of 2.2 times greater than unapposed P/F-terminals. In addition, at peak levels, the proportion of labelled S-terminals that were detached from somata and dendrites was significantly greater than unapposed, labelled P/F-terminals. Axotomy did not alter the caliber of the labelled axon terminals. However, by 29 days after axotomy, the average diameter of dendrites remaining in contact with SPVN terminals was 1/3 the diameter of dendrites of uninjured neurons apposed to labelled axon terminals. These findings provide the morphological correlate for physiological and pharmacological evidence that the effectiveness of excitatory and inhibitory synapses are down-regulated in a coordinated manner after hypoglossal nerve injury.     

Matrix metalloproteinase-9 deficiency impairs host defense mechanisms against Streptococcus pneumoniae in a mouse model of bacterial meningitis

Recent reports of human immunodeficiency virus-1 (HIV-1) infection of astrocytes suggest a role for astrocytes in HIV encephalitis. In this study, we infected a human astrocytoma cell line with a pathogenic simian HIV (SHIV_50OLNV) and examined growth patterns and immunomodulatory genes. Approximately 1% of uninfected cells in culture expressed glial fibrillary acid protein (GFAP) whereas 40% of the cells expressed GFAP at 7 days post-inoculation along altered growth patterns. Using targeted cytokine cDNA arrays, we found that SHIV_50OLNV infection resulted in the up-regulation of several genes including metalloproteinase bone morphogenic protein 1 and chemokines monocyte chemoattractant protein 1 and stromal cell derived factor 1. These data suggest that astrocytic activation, altered morphology and up-regulation of immunomodulatory genes in response to SHIV infection may participate in initiation of inflammation and trafficking of infected monocytes/macrophages into the central nervous system, potentiating the development of HIV encephalitis.     

Retinoids and spermatogenesis: lessons from mutant mice lacking the plasma retinol binding protein.

Using Rbp4-null mice as models, we have established for the first time the kinetics of the spermatogenetic alterations during vitamin A deficiency (VAD). Our data demonstrate that the VAD-induced testicular degeneration arises through the normal maturation of germ cells in a context of spermatogonia differentiation arrest. They indicate that retinoic acid (RA) appears dispensable for the transition of premeiotic to meiotic spermatocytes, meiosis, and spermiogenesis. They confirm that RA plays critical roles in controlling spermatogonia differentiation, spermatid adhesion to Sertoli cells, and spermiation, and suggest that the VAD-induced arrest of spermatogonia differentiation results from simultaneous blocks in RA-dependent events mediated by RA receptor gamma (RARgamma) in spermatogonia and by RARalpha in Sertoli cells. They also provide evidence that expression of major RA-metabolizing enzymes is increased in mouse Sertoli cells upon VAD and that vitamin A-deficient A spermatogonia differ from their RA-sufficient counterparts by the expression of the Stra8 gene.     

Decreased virulence of a pneumolysin-deficient strain of Streptococcus pneumoniae in murine meningitis

Pneumolysin, neuraminidases A and B, and hyaluronidase are virulence factors of Streptococcus pneumoniae that appear to be involved in the pathogenesis of meningitis. In a murine model of meningitis after intracerebral infection using mutants of S. pneumoniae D39, only mice infected with a pneumolysin-deficient strain were healthier at 32 and 36 h, had lower bacterial titers in blood at 36 h, and survived longer than the D39 parent strain. Cerebellar and spleen bacterial titers, meningeal inflammation, and neuronal damage scores remained uninfluenced by the lack of any of the virulence factors.     

Enzyme Immunoassay Detecting Teichoic and Lipoteichoic Acids versus Cerebrospinal Fluid Culture and Latex Agglutination for Diagnosis of Streptococcus pneumoniae Meningitis

A newly developed enzyme immunoassay (EIA) was used to detect the presence of pneumococcal teichoic and lipoteichoic acids in cerebrospinal fluid (CSF) from patients with Streptococcus pneumoniae meningitis who were being treated with antibiotics. All initial CSF samples, which on culture grew S. pneumoniae, were positive in the EIA. A total of 14 subsequent culture-negative samples gave clear signals in the EIA up to day 15 after the onset of antibiotic treatment. For 11 CSF specimens, culture, microscopy, and latex agglutination were negative while the EIA detected pneumococcal antigens. The EIA did not react either with CSF of patients with meningitis caused by bacteria other than S. pneumoniae or by viral pathogens. In conclusion, this EIA can be a valuable tool for the diagnosis of S. pneumoniae meningitis from CSF samples in cases in which prior antimicrobial therapy minimizes the usefulness of culture or other antigen detection tests.     

Spatial memory and learning deficits after experimental pneumococcal meningitis in mice

Survivors of bacterial meningitis frequently suffer from long-term sequelae, particularly from learning and memory deficits. For this reason, spatial memory and learning was studied in a mouse model of ceftriaxone-treated Streptococcus pneumoniae meningitis. Persistent deficits of spatial learning despite normal motor function were observed in mice infected with 10(4) colony-forming units (CFU) in 25 microl of saline into the right forebrain in comparison to mice treated with an equal amount of saline. Survivors of meningitis performed significantly worse in memorizing a hidden platform in a Morris water maze. After 2 weeks, the difference between post-meningitis and control mice diminished. Yet, when the platform was moved after 180 days, learning of the new location was still strongly impaired in mice surviving meningitis.     

Molecular cloning, genomic structure and localization in a blood stage antigen of Plasmodium falciparum characterized by a serine stretch

Two short DNA segments were isolated by screening of a lambda gt11 library from Plasmodium falciparum schizont cDNA with an antiserum against the 140 kDa protein, which confers protective immunity to monkeys. The segments were used to identify a genomic fragment which carries the entire coding sequence for a protein of 113 kDa characterized by a stretch of serine residues (SERP I). We present the complete nucleotide and deduced amino acid sequence as well as the structure of the SERP I gene. The gene consists of four exons interrupted by three short introns located at the amino-terminal half. Exon 1 and the first part of exon 2 code for hydrophobic amino acids of a putative signal sequence. Exon 2 contains two repetitive segments, the first encoding six glycine rich octapeptides and a second region coding for 37 consecutive serine residues. Southern blot analysis demonstrated the conservation of the SERP I gene in four different parasite strains. SERP I could be localized in the parasitophorous vacuole and in the surrounding membranes. We discuss the relationship of this protein to the recently described P126 polypeptide and the possible role of this antigen as a vaccine candidate.     

Evaluation of temperature distributions in cadaveric lumbar spine during nucleoplasty

In this study, temperature maps were obtained throughout human cadaveric disc specimens (n = 6) during a simulated Nucleoplasty treatment. The procedure was performed using the Perc-DL SpineWand (ArthroCare, Sunnyvale, CA) inserted through a 17 gage needle into the human cadaveric disc. The device uses a dual mode heating technique which employs a high voltage radio frequency (RF) plasma field to vaporize tissue (Coblation), followed by bipolar RF current heating for thermal coagulation. The device, with a distal 's-curve', is manipulated manually to create a series of six channels at a 60 degrees angular spacing within a period of 3 min. A computer-controlled, motorized translational system was used to reproducibly mimic the insertion (Coblation) and retraction (rf-coagulation) performed during clinical implementation, with rotation performed manually between each Coblation/coagulation cycle. Transient temperature data were obtained using five multi-junction thermocouple probes (5-8 junctions spaced at either 2 or 5 mm intervals, with 0.33 or 0.56 mm probe diameter) spaced throughout the desired heating volume. Transient temperature curves were obtained from 26+ points throughout the disc, and the data used to calculate accumulated thermal doses. Transient peaks of 80-90 degrees C were recorded within the discs, with temperatures greater than 60-65 degrees C measured within a radial distance of 3-4 mm from the introducer (applicator centreline). Accumulated thermal doses of t43 > 250 min were produced at radial distances of up to 6 mm from the introducer. Gross inspection of the discs revealed a narrow region of coagulation along the insertion length. Given these radial thermal penetrations and the possibility for unpredictable positioning during current clinical implementation, high temperatures and lethal thermal doses in small regions outside of the nucleus, or within the bone endplates, may be possible in clinical implementation.