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1.
Neurology ; 67(7): 1221-4, 2006 Oct 10.
Article in English | MEDLINE | ID: mdl-17030756

ABSTRACT

OBJECTIVE: To determine whether cognitively intact adults with the APOE epsilon3/epsilon4 genotype show reduced gray matter density on voxel-based morphometry (VBM) vs those homozygous for the epsilon3 allele. METHODS: Participants were healthy, cognitively intact, right-handed adults, age 19 to 80, who completed genotyping, neuropsychological testing, and MRI. Forty-nine participants had the epsilon3/epsilon3 genotype and 27 had the epsilon3/epsilon4 genotype. Gray matter data were analyzed using the general linear model as implemented in the Statistical Parametric Mapping package, adjusting for age and sex. RESULTS: The epsilon3/epsilon4 participants showed lower gray matter density than the epsilon3/epsilon3 participants in right medial temporal and bilateral frontotemporal regions as well as other areas. There were no regions in which epsilon3/epsilon4 participants showed higher gray matter density than epsilon3/epsilon3 participants. CONCLUSIONS: Regionally reduced gray matter density is detectable in cognitively intact adults with a single copy of the APOE epsilon4 allele.


Subject(s)
Apolipoproteins E/genetics , Brain/metabolism , Brain/pathology , Genetic Predisposition to Disease/genetics , Neurons/pathology , Adult , Aged , Aged, 80 and over , Apolipoprotein E4 , Atrophy/diagnosis , Atrophy/genetics , Cognition Disorders/diagnosis , Cognition Disorders/genetics , DNA Mutational Analysis , Female , Gene Frequency , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Mutation
2.
Epilepsia ; 42(7): 883-8, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11488888

ABSTRACT

PURPOSE: High-resolution magnetic resonance imaging (MRI) plays a crucial role in the presurgical evaluation of patients with medically refractory partial epilepsy. Although MRI detects a morphologic abnormality as the cause of the epilepsy in the majority of patients, some patients have a normal MRI. This study was undertaken to explore the hypothesis that in patients with normal MRI, invasive monitoring can lead to localization of the seizure-onset zone and successful epilepsy surgery. METHODS: A series of 115 patients with partial epilepsy who had undergone intracranial electrode evaluation (subdural strip, subdural grid, and/or depth electrodes) between February 1992 and February 1999 was analyzed retrospectively. Of these, 43 patients (37%) had a normal MRI. RESULTS: Invasive monitoring detected a focal seizure onset in 25 (58%) patients, multifocal seizure origin in 12 (28%) patients, and in six patients, no focal seizure origin was found. Of the 25 patients with a focal seizure origin, cortical resection was performed in 24, of whom 20 (83%) had a good surgical outcome with respect to seizure control. Six of the 12 patients with multifocal seizure origin underwent other forms of epilepsy surgery (palliative cortical resection in two, anterior callosotomy in two, and vagal nerve stimulator placement in two). CONCLUSIONS: Successful epilepsy surgery is possible in patients with normal MRIs, but appropriate presurgical evaluations are necessary. In patients with evidence of multifocal seizure origin during noninvasive evaluation, invasive monitoring should generally be avoided.


Subject(s)
Cerebral Cortex/surgery , Epilepsies, Partial/diagnosis , Epilepsies, Partial/surgery , Magnetic Resonance Imaging/statistics & numerical data , Adolescent , Adult , Cerebral Cortex/pathology , Electrodes, Implanted , Electroencephalography/statistics & numerical data , Epilepsies, Partial/pathology , Epilepsy, Frontal Lobe/diagnosis , Epilepsy, Frontal Lobe/surgery , Epilepsy, Temporal Lobe/diagnosis , Epilepsy, Temporal Lobe/surgery , Female , Humans , Male , Middle Aged , Preoperative Care , Retrospective Studies , Technetium Tc 99m Exametazime , Tomography, Emission-Computed, Single-Photon/statistics & numerical data , Treatment Outcome
3.
Cytogenet Cell Genet ; 82(3-4): 192-4, 1998.
Article in English | MEDLINE | ID: mdl-9858814

ABSTRACT

Pericentromeric polymorphisms of chromosome 9 include variations in the size of heterochromatin, pericentric inversions, and, more rarely, additional C-band-negative, G-band-positive material in either the proximal short arm or long arm or within the heterochromatin. It has been postulated that rearrangements involving the different classes of satellite DNA present in this relatively unstable region of the human genome constitute a mechanism for the origin of these variants. We report the identification, by molecular cytogenetic investigations, of homologous stretches of euchromatin shared by the proximal short and long arms of chromosome 9 that suggest that exchanges involving these regions may be an additional mechanism for the origin of chromosome 9 polymorphisms.


Subject(s)
Centromere/genetics , Chromosomes, Human, Pair 9 , Polymorphism, Genetic , Chromatin , DNA, Satellite/analysis , Humans , In Situ Hybridization, Fluorescence , Sequence Homology, Nucleic Acid
4.
Clin Neuropathol ; 16(6): 328-31, 1997.
Article in English | MEDLINE | ID: mdl-9401800

ABSTRACT

Traditional views of pure alexia have held that the disorder results from a disconnection between the secondary visual cortices of both hemispheres and the angular gyrus of the dominant hemisphere. Evidence has accumulated, however, suggesting the importance of the posterior inferior temporal area in visual language processing. We describe clinical-pathological support for the presence of a lateralized visual language association area residing in the dominant posterior inferior temporal lobe.


Subject(s)
Dyslexia, Acquired/pathology , Functional Laterality/physiology , Visual Cortex/pathology , Female , Humans , Language , Middle Aged , Temporal Lobe/pathology
5.
Diagn Mol Pathol ; 6(1): 49-57, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9028737

ABSTRACT

PCR assays for the presence of mutant K-ras or p53 sequences are potentially useful as sensitive tests for tumor diagnosis. The technical challenge is to design assays sensitive enough to detect a few molecules of mutant DNA yet sufficiently specific that a false positive signal is not produced by a 10(5)- or 10(6)-fold excess of normal DNA. We determined the detection limit of allele-specific PCR (ASA) as a function of the particular mismatch involved using all 12 possible mismatches in two different DNA sequence contexts (K-ras codon 12 and p53 codon 273). Depending on the identity of the mismatch, mismatched template was amplified 10(2)-10(4)-fold less than perfectly matched template. In other words, a mutant allele could be detected by ASA if it represented > 1-0.01% of the total DNA from that locus. Peptide nucleic acid (PNA) clamping was used to improve the K-ras ASA assay. Selective amplification of mutant sequences was achieved using a PNA complementary to the normal sequence to inhibit the amplification of wild-type DNA. PNA clamping followed by ASA resulted in significant improvement in sensitivity and specificity, permitting the detection of tumor DNA diluted with a 300,000-fold excess of normal human DNA.


Subject(s)
Alleles , Neoplasms/diagnosis , Neoplasms/genetics , Polymerase Chain Reaction/methods , DNA Primers , DNA-Directed DNA Polymerase/chemistry , DNA-Directed DNA Polymerase/genetics , Genes, p53 , Genes, ras , Humans , Mutation , Peptide Fragments/genetics , Taq Polymerase , Templates, Genetic
6.
Cytogenet Cell Genet ; 78(3-4): 247-52, 1997.
Article in English | MEDLINE | ID: mdl-9465898

ABSTRACT

We previously described a patient with a de novo constitutional translocation, t(1;22)(p22;q11.2), who developed a malignant ependymoma at age 5, and we proposed that the translocation predisposed the child to the development of the tumor. As a step toward isolation of a putative cancer gene, we have characterized the breakpoints of the (1;22) translocation at the molecular level. The chromosome 22 breakpoint has been narrowed to a region between ARVCF and D22S264. The chromosome 1 breakpoint has been mapped onto a doubly-linked Whitehead YAC contig by PCR analysis of the STS contents of the patient's derivative chromosomes isolated in somatic cell hybrids. Loss-of-heterozygosity (LOH) studies of the patient's ependymoma and of sporadic ependymomas showed no evidence of consistent loss in the breakpoint regions, suggesting that activation of an oncogene, rather than inactivation of a tumor suppressor gene, is the more likely molecular mechanism involved in this case. The gene for Edg-1, a neurally expressed, seven-segment transmembrane receptor, maps to the region of the chromosome 1 breakpoint but does not appear to be interrupted by the translocation. Molecular characterization of the breakpoint regions reported here represents an important step in the identification of the gene(s) affected by this translocation.


Subject(s)
Brain Neoplasms/genetics , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 22 , Ependymoma/genetics , Receptors, G-Protein-Coupled , Translocation, Genetic , Animals , Child, Preschool , Chromosome Mapping , Chromosomes, Artificial, Yeast , Cricetinae , Genetic Carrier Screening , Humans , Hybrid Cells , Immediate-Early Proteins/genetics , In Situ Hybridization, Fluorescence , Male , Receptors, Cell Surface/genetics , Receptors, Lysophospholipid
7.
Semin Oncol ; 23(6 Suppl 16): 128-35, 1996 Dec.
Article in English | MEDLINE | ID: mdl-9007140

ABSTRACT

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has shown in vitro and clinical activity against non-small cell lung cancer and astrocytic brain tumors, tumors traditionally thought of as relatively resistant to chemotherapy and radiotherapy. Because of its ability to block dividing cells in the G2/M portion of the cell cycle (the most radiosensitive phase of the cell cycle), paclitaxel is also a potentially potent radiosensitizer. To exploit these and other properties of paclitaxel, we explored a weekly, outpatient administration schedule, with and without concurrent radiation therapy, in patients with non-small cell lung cancer and astrocytic brain tumors. Our experience has shown that weekly outpatient administration is feasible, that remarkably high dose intensities can be achieved with acceptable toxicity, and that the specific dose-limiting toxicity appears to depend on administration schedule, type of concurrent radiotherapy, and certain patient characteristics. Preliminary response data are very encouraging. At the same time, pharmacokinetic studies have suggested possible reasons for our ability to use such exorbitant dose intensities safely, and also have shown that sustained plasma paclitaxel levels above the putative radiosensitizing threshold can be achieved continuously during a 6-week course of radiotherapy. Specific results, dosing recommendations, and plans for future studies are discussed.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Astrocytoma/therapy , Brain Neoplasms/therapy , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Paclitaxel/administration & dosage , Radiation-Sensitizing Agents/administration & dosage , Adult , Aged , Aged, 80 and over , Ambulatory Care , Antineoplastic Agents, Phytogenic/pharmacokinetics , Antineoplastic Agents, Phytogenic/toxicity , Astrocytoma/drug therapy , Brain Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Combined Modality Therapy , Drug Administration Schedule , Female , Humans , Lung Neoplasms/drug therapy , Male , Middle Aged , Paclitaxel/pharmacokinetics , Paclitaxel/toxicity , Radiation-Sensitizing Agents/pharmacokinetics , Radiation-Sensitizing Agents/toxicity , Radiotherapy Dosage , Tumor Suppressor Protein p53/analysis
8.
Cancer Genet Cytogenet ; 92(1): 4-7, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8956861

ABSTRACT

A four and a half year old male was diagnosed with desmoplastic infantile ganglioglioma. To our knowledge, the cytogenetics of this tumor have never been reported. In our analysis of 40 cells, no consistent clonal abnormalities were observed; however, the majority of cells (25 of 40) showed structural rearrangements (telomere associations) resulting in dicentrics and other derivative chromosomes. Breakpoints most often observed included 17q25 (6 of 40), 19p13.3 (4 of 40), 17p13 (3 of 40), 14q32 (3 of 40), 11q25 (3 of 40), 9p24 (2 of 40), 5q35 (2 of 40), and 22q13 (2 of 40).


Subject(s)
Brain Neoplasms/genetics , Cerebral Cortex , Chromosome Breakage/genetics , Ganglioglioma/genetics , Telomere/genetics , Translocation, Genetic/genetics , Brain Neoplasms/pathology , Child, Preschool , Ganglioglioma/pathology , Humans , Male
9.
Arch Pathol Lab Med ; 120(3): 254-60, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8629900

ABSTRACT

OBJECTIVE AND DESIGN: Non-Hodgkin's lymphomas rarely present as a localized mass involving the dura. In this report we describe the clinical, histologic, and immunohistochemical features of five cases of stage IE non-Hodgkin's lymphoma involving the dura. PATIENTS: Four women and one man, 36 to 67 years of age (median 50.6 years). RESULTS: Myelography and magnetic resonance imaging scans revealed discrete expansile masses involving the dura of the cervical, thoracic, and lumbar regions of the spinal cord and the frontal lobe of the brain. Histologically, the tumors were classified in the Working Formulation as small lymphocytic (2), diffuse large cell (2), and large cell immunoblastic (1) (anaplastic large cell lymphoma). Four tumors were of B-cell lineage and the anaplastic large-cell lymphoma was of T-cell lineage. The two small lymphocytic neoplasms had immunoglobulin heavy-chain gene rearrangements as shown by either Southern blot hybridization or the polymerase chain reaction. Four patients underwent decompression laminectomy; three received spinal radiation; two received chemotherapy (one intrathecal, one systemic) for lymphocytosis of the cerebrospinal fluid. The dural mass overlying the frontal lobe was excised and focally irradiated. Clinical follow-up was available for all patients. Four patients were alive 12 to 40 months after diagnosis and showed no evidence of recurrent or disseminated disease. The patient with anaplastic large-cell lymphoma died 10 days after laminectomy, secondary to pulmonary thromboemboli. CONCLUSIONS: We conclude that non-Hodgkin's lymphomas of varied histologic types and of either B- or T-cell lineage may rarely present as a stage IE dural mass. These lesions appear to have a good initial response to treatment; however, longer clinical follow-up is necessary to assess the incidence of relapse and final outcome.


Subject(s)
Dura Mater/pathology , Frontal Lobe/pathology , Lymphoma, Non-Hodgkin/pathology , Spinal Cord/pathology , Adult , Aged , Antigens, CD/analysis , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Lymphoma, Non-Hodgkin/immunology , Male , Middle Aged , Survival Rate
10.
Cancer Genet Cytogenet ; 86(2): 150-2, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8603343

ABSTRACT

There is a body of evidence suggesting the presence of a tumor suppressor gene on chromosome 22 which plays a role in the pathogenesis of ependymomas. We report a patient with a de novo constitutional t(1;22)(p22;q11.2) who developed a malignant ependymoma at age 5. The patient is otherwise phenotypically normal. By fluorescence in situ hybridization (FISH) analysis, the chromosome 22 breakpoint has been localized to the region between the DiGeorge locus and BCR. Since NF2 and EWS are both distal to BCR, the are presumable not involved in this rearrangement. This patient may offer a unique opportunity to identify the chromosome 22 ependymoma tumor suppressor gene by cloning the translocation breakpoint.


Subject(s)
Brain Neoplasms/genetics , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 22 , Ependymoma/genetics , Translocation, Genetic , Child , Chromosome Mapping , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Male
11.
J Clin Oncol ; 14(2): 600-9, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8636777

ABSTRACT

PURPOSE: Astrocytomas are extremely resistant to currently available treatments. Cranial irradiation is a mainstay of frontline therapy, but tumor recurrence is nearly universal. Paclitaxel has shown antitumor efficacy against astrocytoma cell lines, and is a potent radiosensitizer. For these reasons, we conducted a phase I study of weekly paclitaxel and concurrent cranial irradiation in patients with newly diagnosed astrocytomas. PATIENTS AND METHODS: Patients with astrocytomas were eligible for this study following initial surgery if they had a Karnofsky performance score (KPS) > or = 60%; normal hematologic, liver, and renal function; and could give informed consent. Beginning on day 1 of treatment, patients received paclitaxel by 3-hour infusion once weekly for 6 weeks, concurrent with standard cranial irradiation. Pharmacokinetic studies were performed on 10 patients. RESULTS: Sixty patients were enrolled; 56 were fully assessable. Forty-eight had glioblastomas (GBMs), 10 anaplastic astrocytomas (AAs), and two astrocytomas. Age ranged from 21 to 81 years (median, 55); KPS ranged from 60 to 100 (median, 70). The paclitaxel dose was escalated from 20 mg/m2 to 275 mg/m2. No clinically significant anemia or thrombocytopenia occurred. Only one patient (175 mg/m2) became neutropenic. Sensory neuropathy was dose-limiting. The maximum tolerated dose (MTD) was 250 mg/m2. Paclitaxel pharmacokinetic profiles in study patients were identical to those of previously reported patients with other solid tumors. CONCLUSION: The MTD of paclitaxel administered weekly for 6 weeks by 3-hour infusion is 250 mg/m2. Since patients with brain tumors often have preexisting neurologic deficits, we suggest 225 mg/m2 as the optimum dose for phase II trials in this group of patients.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Astrocytoma/therapy , Brain Neoplasms/therapy , Paclitaxel/administration & dosage , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/pharmacokinetics , Astrocytoma/radiotherapy , Brain Neoplasms/radiotherapy , Combined Modality Therapy , Drug Administration Schedule , Glioblastoma/therapy , Humans , Middle Aged , Paclitaxel/adverse effects , Paclitaxel/pharmacokinetics
12.
Cancer ; 77(3): 543-8, 1996 Feb 01.
Article in English | MEDLINE | ID: mdl-8630963

ABSTRACT

BACKGROUND: Inherent limitations of conventional cytology often result in a failure to diagnose lymphomatous meningitis in cerebrospinal fluid (CSF) specimens from patients who actually have the disease. The development of polymerase chain reaction (PCR) techniques for the diagnosis of lymphoma based on the detection of clonal rearrangements of the immunoglobulin or T-cell receptor genes offers an alternative, DNA-based test for the diagnosis of lymphoma in the CSF. METHODS: In this retrospective study, 31 CSF specimens from 21 patients were examined by a PCR technique that can detect clonal immunoglobulin gene rearrangements. Twenty-four of the specimens came from 14 patients who eventually had definitive histologic or cytologic diagnoses of B-cell lymphoma. The other seven patients had other neurologic diagnoses, including two patients with reactive lymphocytosis, three with glioblastoma, one with metastatic carcinoma, and one with multi-infarct dementia. The results of the PCR examinations were compared with cytologic evaluation of the same CSF specimens. RESULTS: Five of seven specimens from patients with central nervous system lymphoma that were suspicious for, but not diagnostic of, lymphoma by conventional cytology were positive by PCR. Of 13 specimens from patients with lymphoma that showed no cytologic evidence of malignancy, 5 were positive by PCR. Two of four specimens for which conventional cytology showed definitive evidence of lymphoma were positive by PCR. Two specimens from patients with a reactive lymphocytosis showed a polyclonal pattern by PCR. Specimens from patients with other neurologic diseases were negative by PCR even when cytologically malignant (glioblastoma) cells were present in the specimen. CONCLUSIONS: PCR examination of CSF is practical, complements conventional cytology, and sometimes provides the correct diagnosis when conventional cytology yields only ambiguous results.


Subject(s)
Lymphoma/cerebrospinal fluid , Lymphoma/diagnosis , Meningitis/cerebrospinal fluid , Meningitis/diagnosis , Base Sequence , Cytological Techniques , Humans , Molecular Sequence Data , Retrospective Studies
13.
N Engl J Med ; 334(2): 125, 1996 Jan 11.
Article in English | MEDLINE | ID: mdl-8531957
14.
Am J Clin Pathol ; 103(4): 404-8, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7726135

ABSTRACT

The sensitivity of polymerase chain reaction (PCR)-based methods for the detection of DNA offers opportunities for tumor diagnosis from the small amounts of tumor-derived DNA released into body fluids. Tumor-derived DNA can be distinguished from DNA derived from non-neoplastic cells by the presence of tumor specific genomic alterations, such as mutations in the p53 gene. This case report describes the use of allele-specific PCR (A-PCR) to detect a C-->T transition in p53 codon 273 in DNA extracted from the cerebrospinal fluid (CSF) of a patient whose glioblastoma contained the same mutation. The results of this study were confirmed by a second independent A-PCR reaction that detected the corresponding G-->A transition on the opposite strand. The specificity of the A-PCR protocol was demonstrated by negative controls, including pooled human placental DNA and the patient's non-tumor DNA, and by the use of A-PCR primers to detect all four possible bases at the site of the mutation. The methodology used in this study is suitable for use as a diagnostic clinical test. Because about half of all human tumors contain p53 mutations, PCR examination of CSF for the presence of mutant p53 sequences may be useful in the diagnosis of recurrent or metastatic tumors. Patients with known carcinoma of the breast or lung might be particularly benefited by this test.


Subject(s)
Brain Neoplasms/cerebrospinal fluid , DNA, Neoplasm/cerebrospinal fluid , Glioblastoma/cerebrospinal fluid , Tumor Suppressor Protein p53/genetics , Adolescent , Base Sequence , Brain Neoplasms/genetics , Exons , Glioblastoma/genetics , Humans , Male , Molecular Sequence Data , Mutation , Oligonucleotide Probes/genetics , Polymerase Chain Reaction , Sensitivity and Specificity
15.
J Neuropathol Exp Neurol ; 53(4): 364-8, 1994 Jul.
Article in English | MEDLINE | ID: mdl-7912724

ABSTRACT

The sensitivity of PCR-based methods for the detection of DNA offers opportunities for tumor diagnosis from the small amounts of tumor-derived DNA released into body fluids. We report the detection of tumor DNA in the cerebrospinal fluid (CSF) of two patients with intracranial neoplasms. One patient had a metastatic breast carcinoma which contained amplified HER-2/neu genes, and amplified HER-2/neu gene sequences were present in her CSF. The other patient had a glioblastoma which contained amplified epidermal growth factor receptor (EGFR) genes, and amplified EGFR gene sequences were present in her CSF. This report demonstrates that CSF sometimes contains tumor-derived DNA and suggests that PCR examination of CSF DNA may be diagnostically useful.


Subject(s)
Brain Neoplasms/cerebrospinal fluid , Breast Neoplasms/cerebrospinal fluid , Carcinoma, Ductal, Breast/cerebrospinal fluid , DNA, Neoplasm/cerebrospinal fluid , Glioblastoma/cerebrospinal fluid , Aged , Aged, 80 and over , Brain Neoplasms/secondary , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/secondary , ErbB Receptors/genetics , Female , Gene Amplification , Humans , Proto-Oncogene Proteins/genetics , Receptor, ErbB-2
17.
Brain Res ; 617(2): 238-48, 1993 Jul 23.
Article in English | MEDLINE | ID: mdl-8402152

ABSTRACT

Recent studies suggest that brain ependyma and choroid plexus produce neuropeptide processing enzymes. To facilitate the understanding of these cells and their ability to produce biologically active peptides, we developed cultures of defined cell type. Ependymal cells were characterized by morphological criteria, and choroid plexus epithelial cell lines were characterized by the presence of the mRNA for IGF-II and transthyretin, a thyroxine binding protein produced in liver and choroid plexus. The ependymal cells and the choroid plexus epithelial cell lines were then examined for the presence of mRNAs for various neuropeptide processing enzymes. Northern blot analysis revealed high levels of furin, carboxypeptidase E, and peptidyl glycine alpha-amidating monooxygenase mRNAs, with levels in ependymal cells comparable to those in brain or pituitary. Carboxypeptidase E activity was detected in medium from cultured ependymal cells; this activity was identified as carboxypeptidase E based on the acidic pH optimum and sensitivity to various inhibitors. The mRNAs for other neuropeptide processing enzymes, such as prohormone convertases 1 and 2, were not detected on Northern blots of RNA from ependyma or choroid plexus epithelium. Since ependyma and choroid plexus epithelium express a subset of processing enzymes, we suggest that these cells have the capacity to produce biologically active peptides. Initial screening by reverse transcriptase-polymerase chain reaction assays has demonstrated the presence of mRNA for the neurosecretory proteins chromogranin B and secretogranin II in both ependyma and choroid plexus epithelium.


Subject(s)
Choroid Plexus/metabolism , Endopeptidases/biosynthesis , Ependyma/metabolism , Multienzyme Complexes , Nerve Tissue Proteins/biosynthesis , Neuropeptides/metabolism , Neurosecretory Systems/physiology , Proteins , Animals , Base Sequence , Carboxypeptidase H , Carboxypeptidases/biosynthesis , Cells, Cultured , Chromogranins/biosynthesis , Epithelium/metabolism , Furin , Mixed Function Oxygenases/biosynthesis , Molecular Sequence Data , Protein Biosynthesis , RNA, Messenger/analysis , Rats , Rats, Wistar , Subtilisins/biosynthesis
19.
Anesth Analg ; 76(1): 123-30, 1993 Jan.
Article in English | MEDLINE | ID: mdl-8418713

ABSTRACT

Intrathecal application of the enkephalinase inhibitor, SCH 32615, yields antinociception in animal paradigms. Our purpose was to identify possible acute behavioral effects, neurotoxicity, or systemic toxicity of intrathecal SCH 32615 administration during 9 days in the ewe. Seventeen ewes were implanted with lumbar silicone intrathecal catheters and subcutaneous access ports for repeated injection. Baseline and serial daily behavioral assessments were made during 9 days of 2-mL intrathecal injection twice daily of either normal saline (SAL group) or a 20 mg/mL isotonic sterile solution of SCH 32615 (SCH group). Data were analyzed by treatment group (SCH versus SAL) by taking the group means of individual ewe cumulative scores during 9 days. At 15-18 h after the last injection, the ewes were euthanized and the spinal cords and leptomeninges were grossly examined and prepared for histological assessment. Histological evaluation of the lumbar (at catheter entrance site and catheter tip), thoracic, and cervical sections of all animals was performed by two neuropathologists. Several mild, reversible, and apparently nonprogressive behaviors (Stepping/Placing and Hindlimb Stretching/Splaying) were observed almost exclusively in SCH-treated ewes. These behaviors were interpreted as mild temporary irritative effects, without significant neuropathological sequelae. Pathological findings primarily consisted of mild, focal dural thickening and white matter compression. These changes were distributed equally between drug-treated and control groups and were attributable to catheter implantation and local compressive effects. There were no pathological bases identified in this study to preclude the clinical study of SCH 32615 within the dose range studied.


Subject(s)
Dipeptides/toxicity , Gait/drug effects , Neprilysin/antagonists & inhibitors , Animals , Body Weight/drug effects , Dipeptides/administration & dosage , Female , Injections, Spinal , Motor Activity/drug effects , Sheep , Spinal Cord/drug effects , Spinal Cord/pathology
20.
AJNR Am J Neuroradiol ; 13(1): 164-6, 1992.
Article in English | MEDLINE | ID: mdl-1595436

ABSTRACT

We describe the CT appearance of suspected pigmented villonodular synovitis involving a lumbar facet in a 51-year-old woman, and discuss how the histologic and radiologic appearances may differ from those of synovial cysts.


Subject(s)
Lumbar Vertebrae/diagnostic imaging , Synovitis, Pigmented Villonodular/diagnostic imaging , Female , Humans , Lumbar Vertebrae/pathology , Middle Aged , Synovitis, Pigmented Villonodular/pathology , Tomography, X-Ray Computed
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