Adaptive femtosecond laser-induced breakdown spectroscopy of uranium.

Laser-induced breakdown spectroscopy (LIBS) is an established technique for material characterization applicable to a variety of problems in research, industry, environmental studies, and security. LIBS conducted with femtosecond laser pulses exhibits unique properties, arising from the characteristics of laser-matter interactions in this pulse width regime. The time evolution of the electric field of the pulse determines its interaction with sample materials. We present the design and performance of a femtosecond LIBS system developed to systematically optimize the technique for detection of uranium. Sample analysis can be performed in vacuum environment, and the spectral and temporal diagnostics are coupled through an adaptive feedback loop, which facilitates optimization of the signal-to-noise ratio by pulse shaping. Initial experimental results of LIBS on natural uranium are presented.

Detection of an estrogen receptor in two nematode species and inhibition of binding and development by environmental chemicals.

The presence of estrogen receptors or binding proteins was demonstrated in the free-living nematode species Panagrellus redivivus and Caenorhabditis elegans by radioimmunoassay. Twenty-five nanomolar concentrations of toxaphene, dieldrin, and dieldrin plus nonylphenol significantly inhibited estrogen binding to the receptor in P. redivivus. Binding was inhibited but not significantly by 25 nM nonylphenol, toxaphene plus dieldrin, or toxaphene plus nonylphenol. The current research supports the hypothesis that dieldrin, nonylphenol, and toxaphene may mimic estrogen, altering the normal pathways of estrogen metabolism. Based on observations of secondary sex structures, estrogenic chemicals had no effect on sex ratios or growth in Panagrellus redivivus, but caused a reduction of fecundity in this nematode.

Chromosome 20 deletions in myeloid malignancies: reduction of the common deleted region, generation of a PAC/BAC contig and identification of candidate genes. UK Cancer Cytogenetics Group (UKCCG).

Deletion of the long arm of chromosome 20 represents the most common chromosomal abnormality associated with the myeloproliferative disorders (MPDs) and is also found in other myeloid malignancies including myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). Previous studies have identified a common deleted region (CDR) spanning approximately 8 Mb. We have now used G-banding, FISH or microsatellite PCR to analyse 113 patients with a 20q deletion associated with a myeloid malignancy. Our results define a new MPD CDR of 2.7 Mb, an MDS/AML CDR of 2.6 Mb and a combined 'myeloid' CDR of 1.7 Mb. We have also constructed the most detailed physical map of this region to date--a bacterial clone map spanning 5 Mb of the chromosome which contains 456 bacterial clones and 202 DNA markers. Fifty-one expressed sequences were localized within this contig of which 37 lie within the MPD CDR and 20 within the MDS/AML CDR. Of the 16 expressed sequences (six genes and 10 unique ESTs) within the 'myeloid' CDR, five were expressed in both normal bone marrow and purified CD34 positive cells. These data identify a set of genes which are both positional and expression candidates for the target gene(s) on 20q.

Identification of multiple copies of a 20q-chromosome in a case of myelodysplastic syndrome: a FISH study.

In myelodysplastic syndromes (MDS) karyotypic aberrations identify subgroups of patients with distinct clinical-morphological features and can be relevant in risk assessment of developing leukemia. Often conventional cytogenetic analysis is not sufficiently informative due to the presence of partially or completely unrecognizable chromosome markers. By chromosome microdissection (MD) and fluorescence in situ hybridization (FISH) we investigated the nature of a karyotypic marker occurring in multiple copies in one case of MDS arisen in a patient previously treated for breast cancer. Results showed dicentrics derived from telomeric fusion between interstitially deleted 20q-chromosomes. The abnormal karyotype resulted into polysomy for a deleted chromosome 20q.

Lead resistance and sensitivity in Staphylococcus aureus.

Five lead-resistant strains of Staphylococcus aureus were isolated. Plasmid-free lead-sensitive variants were obtained from the three plasmid-bearing strains. Lead-resistant strains tolerated an approximately 600 x higher Pb(NO3)2 concentration than lead-sensitive strains. Both types of strains initially bound lead, but only the resistant strains accumulated the metal as an intracellular lead-phosphate.

Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy.

We examined binding to excitatory amino acid and inhibitory amino acid receptors in frozen hippocampal sections prepared from surgical specimens resected from 8 individuals with medically refractory temporal lobe epilepsy. The excitatory receptors studied included N-methyl-D-aspartate (NMDA), strychnine-insensitive glycine, phencyclidine, and quisqualate. The inhibitory receptors studied were gamma-aminobutyric acid type A (GABAA) and benzodiazepine. Excitatory and inhibitory amino acid receptor binding were differentially altered in the patients with temporal lobe epilepsy in comparison to 8 age-comparable autopsy control subjects, and changes in receptor binding were regionally selective in four areas. Binding to phencyclidine receptors associated with the NMDA channel was reduced by 35 to 70% in all regions in the hippocampi of the patients. In contrast, binding to the NMDA recognition site and its associated glycine modulatory site was elevated by 20 to 110% in the cornu ammonis (CA) 1 area and dentate gyrus of the hippocampus of the patients. Binding to these sites was unaffected in area CA4. Binding to the quisqualate-type excitatory amino acid receptor was unchanged in all regions except the stratum lacunosum moleculare CA1, where it was increased by 63%. GABAA and benzodiazepine receptor binding was reduced by 20 to 60% in CA1 and CA4, but unchanged in dentate gyrus. The data indicate that excitatory and inhibitory amino acid receptors are altered in the hippocampus of patients with temporal lobe epilepsy.

Polarity reversal of N20 and P23 somatosensory evoked potentials between scalp and depth recordings.

From depth and scalp electrodes, we recorded MN-SSEPs of a 33-year-old man with right parietal dysfunction and refractory right temporal seizures. A depth lead with 8 electrodes was implanted deep in each parietal-temporal region. Stimulation and recording parameters followed American EEG Society guidelines. Scalp recordings had well-defined P9, P13-14, N18, N20, and P23 potentials with normal conduction times bilaterally. Depth recordings showed potentials of greater number, voltage, and coherence. P13-14 and N18 were recorded at all depth sites with latencies similar to those at the scalp. N18 had markedly greater voltage and duration near the thalamus, with multiple fast components on its ascending phase. In the deep parietal region there was a positivity corresponding to the scalp N20 and a negative potential equal in latency to scalp P23. These findings support an origin of P13-14 caudal to the thalamus, multiple thalamic and possibly rostral brain-stem generators for N18, and generation of N20 and P23 in sensory cortex of subjacent white matter.

Differences between lateral and mesial temporal metabolism interictally in epilepsy of mesial temporal origin.

We performed interictal [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in 17 patients with well-defined unilateral anterior mesial temporal epileptogenic foci as determined by EEG procedures. Sixteen of these patients subsequently underwent surgical resection of the epileptogenic focus. We measured local cerebral metabolic rates for glucose in mesial and lateral temporal structures and compared them with metabolic rates for analogous regions in 16 healthy normal volunteers and the contralateral hemisphere of the epileptic patients. We found relative hypometabolism ipsilateral to the seizure focus more frequently and to a greater degree in the lateral than in the mesial temporal cortex. Since the physiologic abnormalities involved mesial temporal structures, this observation suggests that functional pathways exist between mesial and lateral temporal cortex normally and that these pathways are altered in epilepsy of mesial temporal origin. Hypometabolism did not correlate well with histologic abnormalities in the surgical specimens.

Intra-arterial bromodeoxyuridine radiosensitization of malignant gliomas.

In the 1950's it was first observed that mammalian cells exposed to the halogenated deoxyuridines were more sensitive to ultraviolet light and radiation than untreated cells. This prompted early clinical trials with bromodeoxyuridine (BUdR) which showed mixed results. More recently, several Phase I studies, while establishing the feasibility of continuous intravenous (IV) infusion of BUdR, have reported significant dose limiting skin and bone marrow toxicities and have questioned the optimal method of BUdR delivery. To exploit the high mitotic activity of malignant gliomas relative to surrounding normal brain tissue, we have developed a permanently implantable infusion pump system for safe, continuous intraarterial (IA) internal carotid BUdR delivery. Since July 1985, 23 patients with malignant brain tumors (18 grade 4, 5 grade 3) have been treated in a Phase I clinical trial using IA BUdR (400-600 mg/m2/day X 8 1/2 weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy/day in 6 1/2 weeks). Following initial biopsy/surgery the infusion pump system was implanted; BUdR infusion began 2 weeks prior to and continued throughout the 6 1/2 week course of radiotherapy. There have been no vascular complications. Side-effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. Myelosuppression requiring dose reduction occurred in one patient. An overall Kaplan-Meier estimated median survival of 20 months has been achieved. As in larger controlled series, histologic grade and age are prognostically significant. We have shown in a Phase I study that IA BUdR radiosensitization is safe, tolerable, may lead to improved survival, and appears to be an efficacious primary treatment of malignant gliomas.

The acute effects of exercise duration on serum lipoprotein metabolism.

The purpose of this study was to determine the effect of exercise duration on lipoprotein responses. Twenty two normolipidemic male volunteers, ages 19-31 yrs (X +/- SEM = 23.1 +/- 2.94) participated in the study. Each was novice a runner (training less than 5 mi/wk). Subjects were assessed for baseline lipid measures of high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), total cholesterol (TC) and triglycerides (TG). They were then evaluated for VO2max and ventilatory threshold (VT). Later they were matched for VO2max and randomly assigned to one of three groups which exercised for 15, 30 or 45 min respectively at a VO2 20% below VT. Subjects were evaluated again for HDL-C, LDL-C, TC and TG from blood samples taken pre-exercise and immediately post-exercise, as well as 1, 24 and 48 hrs post-exercise. A 3 X 4 split plot ANOVA found no difference for any lipid measure during the baseline period. A 3 X 5 split-plot ANOVA (covarying for pre-exercise measures) and post-hoc comparisons of pre- and post-exercise lipid levels indicated no significant differences occurred for either TC, TG or LDL-C measures (p less than 0.05). With respect to HDL-C, the 30 min group had significantly lower HDL-C at the 24 hr measure than did 45 min group (46.41 +/- 1.70 vs 53.34 +/- 1.73 mg.dl-1 respectively). No other differences were found. These findings indicate exercise duration will have an effect on acute responses of lipoprotein following exercise of low intensity.

Specific localization of thallium 201 in human high-grade astrocytoma by microautoradiography.

The ability to accurately distinguish remaining or recurrent high-grade astrocytoma from necrosis or edema following treatment is essential to optimal patient management. Thallium 201 planar gamma-camera imaging has been shown to be helpful in detecting recurrent high-grade astrocytoma; however, due to tissue heterogeneity adjacent to and within tumor, the cellular specificity and quantification of 201Tl uptake are largely unknown. In order to determine which tissues are responsible for the radioisotope uptake, microautoradiographic techniques were used to examine multiple tissue sections from five patients with high-grade astrocytoma. Each patient received 5 mCi of 201Tl i.v. 1 h prior to tumor removal. Additionally, all patients received computerized tomographic and 201Tl planar gamma-camera scans prior to surgery. Following surgery, the excised tissue specimens were tentatively classified by gross pathological examination and then immediately processed for dry mount autoradiography; grain density was determined over regions containing tumor, adjacent and uninvolved brain tissue, necrotic tissue, and background. Highly significant differences were found in grain densities (201Tl uptake) between tumor and uninvolved brain tissue, as well as between uninvolved brain tissue and necrotic tissue; there was no significant difference between background grain density and that in necrotic tissue. Mean grain densities (grains/cm2 +/- 1 SD) across patients were: tumor, 102 +/- 23; adjacent, uninvolved brain tissue, 29 +/- 11; necrotic tissue, 6.2 +/- 1.1; and background, 7.0 +/- 4.1. We conclude that the ability of 201Tl to selectively image high-grade astrocytoma is due to its preferential uptake into tumor cells.

Optic tract injury after anterior temporal lobectomy.

Three patients had complete homonymous hemianopia with clinical and neuroimaging characteristics of ipsilateral optic tract infarction after anterior temporal lobectomy for seizure control. This injury presumably resulted from irritative vasospasm of the anterior choroidal artery. The features of this pure optic tract syndrome should be distinguished from the more common compressive optic tract syndrome which generally also impairs ipsilateral optic nerve function.

Stereotactic management of cystic gliomas of the brain stem.

Although cystic gliomas of the brain stem can be readily aspirated using a stereotactic technique, they will frequently recur, resulting in progressive neurological deficit. Since standard neurosurgical approaches to cystic gliomas of the cerebral hemispheres and cerebellum are difficult to apply to brain stem lesions, modification of these techniques are necessary to provide cyst control with minimal morbidity and mortality. This report, based upon 12 procedures performed on 10 patients with gliomas of the mesencephalon, pons, and medulla, details an approach using aspiration, stereotactically placed cyst catheters, and/or intracavitary irradiation with colloidal chromium phosphorus-32 in addition to external radiation therapy and chemotherapy. Cyst control without mortality or permanent morbidity was obtained in all patients using this multimodality approach.

Products of cells cultured from gliomas. VII. Extracellular matrix proteins of gliomas which contain glial fibrillary acidic protein.

Extracellular matrix (ECM) components of two glial fibrillary acidic protein positive (GFAP+) glioma lines U251 and UM6 were studied by silver stain, morphometry, immunofluorescence, enzyme-linked immunosorbent assay, and biosynthetic labeling. Both GFAP+ lines expressed the following qualitative features in common with previously studied GFAP-negative gliomas: (a) laminin, (b) type IV collagen, (c) extracellular fibrils of silver-reducing collagen (d) pattern of reactivity with lectins. Quantitative differences in GFAP+ glioma proteins included less collagen and more laminin than GFAP-negative gliomas. Sparse collagen of GFAP+ gliomas aggregated as extracellular masses. Individual cells of UM6 simultaneously expressed GFAP and mesenchymal ECM components. Results show qualitative similarities of ECM expression among GFAP+ and negative gliomas suggesting a common lineage of these two glioma cell types and universal expression of two epithelial components of ECM, laminin and type IV collagen, among cultured gliomas. Moreover, there is a diversity of quantity and type of ECM proteins of GFAP+ gliomas with the U251 line most restricted in its expression of ECM components and with UM6 manifesting markers of epithelial and mesenchymal lineage. This diversity suggests a capacity for regulation of phenotypic expression of ECM beyond that explained simply by the presence of two cell types of different lineage.

Stereotactic decompression of a prepontine arachnoid cyst with resolution of precocious puberty.

A case of a prepontine (clival) arachnoid cyst is reported. The patient presented with isosexual precocious puberty. Treatment was initially with fenestration by suboccipital craniectomy, however, definitive treatment was via stereotactic transfrontal placement of a cystoperitoneal shunt. Normalization of endocrine function has occurred and has persisted for 1 year. This case is presented as a contrast to the two approaches for the treatment of arachnoid cysts. The case will be described and the literature reviewed.

Intra-arterial bromodeoxyuridine radiosensitization and radiation in treatment of malignant astrocytomas.

Bromodeoxyuridine (BUdR), a nonhypoxic radiosensitizing drug, is a halogenated pyrimidine analog that is incorporated into the deoxyribonucleic acid of dividing cells in a competitive process with thymidine; BUdR also sensitizes these cells to radiation therapy. Neurons and glial cells have a very low mitotic rate. They will not incorporate BUdR and will not be sensitized. Bromodeoxyuridine is best delivered intra-arterially because of its regional advantage, calculated to be between 6 and 16. An 8-week BUdR infusion is delivered before and during radiation therapy through a permanently implanted pump with a catheter placed retrograde into the external carotid artery. Eighteen patients with malignant glioma (15 grade IV, and three grade III) were entered into a Phase I dose-escalation protocol with BUdR dosages ranging from 400 to 600 mg/sq m/day. The maximum dose that can be tolerated appears to be 400 mg/sq m/day for 8 weeks. The 18 patients entered in this study have a median Kaplan-Meier estimated survival time (+/- standard error of the mean) of 22 +/- 5 months with 11 patients still alive. Three patients are alive at 30, 29, and 21 months after diagnosis with no evidence of tumor on computerized tomography. There have been no vascular complications. Side effects in all patients have included anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, iritis, and nail ridging. Myelosuppression requiring dose reduction occurred in one patient. One patient had a Stevens-Johnson syndrome requiring termination of BUdR. It is concluded that intra-arterial BUdR may improve survival times in patients with malignant gliomas.

From manual to 3-D computerized treatment planning for 125-I stereotactic brain implants.

Aspects of planning for the treatment of high grade primary or recurrent brain tumors with stereotactically placed catheters afterloaded with high activity 125-I seeds are discussed. At our institution, planning has evolved from a simple manual process, which assumed geometric symmetry, through a more advanced manual process, that took advantage of certain mechanical properties of the stereotactic frame used, into a sophisticated, computerized planning approach that includes optimization of the source distribution and 3-D displays. Use of the simple manual method is limited to the rare situations where target volumes are quite regular in shape. The advanced manual method provides some customization for irregularly shaped volumes, but is slow and tedious to implement. The interactive, computerized approach permits identification of target volumes directly on CT slices, reconstructions in arbitrary planes, and optimization of catheter placement, source separation along each catheter, and selection of source strengths from an available inventory. A multi-format display feature which includes a probe's eye view perspective is provided to aid in planning. Integral dose-volume histograms for the target volume point out the advantages in using sophisticated, 3-D, computerized planning systems for these implants.