Search PubMed⌕ Search

Biomedical subjects

P R Cooper

Publications and source records attributed to P R Cooper.

At least 37 records · Page 2Linked to original sources
PubMed1998

Contig maps and genomic sequencing identify candidate genes in the usher 1C locus.

Usher syndrome 1C (USH1C) is a congenital condition manifesting profound hearing loss, the absence of vestibular function, and eventual retinal degeneration. The USH1C locus has been mapped genetically to a 2- to 3-cM interval in 11p14-15.1 between D11S899 and D11S861. In an effort to identify the USH1C disease gene we have isolated the region between these markers in yeast artificial chromosomes (YACs) using a combination of STS content mapping and Alu-PCR hybridization. The YAC contig is approximately 3.5 Mb and has located several other loci within this interval, resulting in the order CEN-LDHA-SAA1-TPH-D11S1310-(D11S1888/KCNC1 )-MYOD1-D11S902D11S921-D11S 1890-TEL. Subsequent haplotyping and homozygosity analysis refined the location of the disease gene to a 400-kb interval between D11S902 and D11S1890 with all affected individuals being homozygous for the internal marker D11S921. To facilitate gene identification, the critical region has been converted into P1 artificial chromosome (PAC) clones using sequence-tagged sites (STSs) mapped to the YAC contig, Alu-PCR products generated from the YACs, and PAC end probes. A contig of >50 PAC clones has been assembled between D11S1310 and D11S1890, confirming the order of markers used in haplotyping. Three PAC clones representing nearly two-thirds of the USH1C critical region have been sequenced. PowerBLAST analysis identified six clusters of expressed sequence tags (ESTs), two known genes (BIR, SUR1) mapped previously to this region, and a previously characterized but unmapped gene NEFA (DNA binding/EF hand/acidic amino-acid-rich). GRAIL analysis identified 11 CpG islands and 73 exons of excellent quality. These data allowed the construction of a transcription map for the USH1C critical region, consisting of three known genes and six or more novel transcripts. Based on their map location, these loci represent candidate disease loci for USH1C. The NEFA gene was assessed as the USH1C locus by the sequencing of an amplified NEFA cDNA from an USH1C patient; however, no mutations were detected.

Bacteriophage P1↗
PubMed1998

Focal dilation and paradoxical collapse of cortical fissures and sulci in patients with normal-pressure hydrocephalus.

OBJECT: The authors describe a subgroup of patients with shunt-proven normal-pressure hydrocephalus (NPH) who presented with focal fissural and sulcal dilation on imaging studies. The specific radiological features and methods of differentiating this condition from cortical atrophy are delineated. METHODS: Normal-pressure hydrocephalus has been described as dilation of the ventricles that is out of proportion to the sulci. Sulcal dilation has been taken as evidence of cortical atrophy and has even been used as a criterion to exclude patients from undergoing a shunting procedure. The authors describe five cases of patients with shunt-proven NPH who presented with focal dilation of cortical fissures and sulci. In three of the cases, there was a paradoxical decrease in the size of the dilated fissures and sulci that paralleled the decrease in the size of the lateral ventricles following successful shunting. CONCLUSIONS: This study demonstrates that focal fissural and sulcal dilation may represent reservoirs of cerebrospinal fluid analogous to the ventricular system. Patients should not be denied a shunting procedure solely on the basis of focally dilated fissures of sulci.

Aged↗
PubMed1997

A 1-Mb physical map and PAC contig of the imprinted domain in 11p15.5 that contains TAPA1 and the BWSCR1/WT2 region.

We have constructed a 1-Mb contig in human chromosomal band 11p15.5, a region implicated in the etiology of several embryonal tumors, including Wilms tumor, and in Beckwith-Wiedemann syndrome. Cosmid, P1, PAC, and BAC clones were characterized by NotI/SalI digestion and hybridized to a variety of probes to generate a detailed physical map that extends from D11S517 to L23MRP. Included in the map are the CARS, NAP2, p57/KIP2, KVLQT1, ASCL2, TH, INS, IGF2, H19, and L23MRP genes as well as end probes isolated from PACs. The TAPA1 gene, whose protein product can transmit an antiproliferative signal, was also localized in the contig. However, Northern blot analysis demonstrated that its expression did not correlate with tumorigenicity in G401 Wilms tumor hybrids, suggesting that TAPA1 is not responsible for the tumor suppression associated with 11p15.5. Genomic clones were used as probes in FISH analysis to map the breakpoints from three Beckwith-Wiedemann syndrome patients and a rhabdoid tumor. Interestingly, each of the breakpoints disrupts the KVLQT1 gene, which is spread over a 400-kb region of the contig. Since 11p15.5 contains several genes with imprinted expression and one or more tumor suppressor genes, our contig and map provide a framework for characterizing this intriguing genetic environment.

Antigens, CD↗
PubMed1997

A sequence-ready high-resolution physical map of the best macular dystrophy gene region in 11q12-q13.

Best disease, an autosomal dominant inherited macular degenerative disorder, was previously localized between D11S1765 and UGB (uteroglobin) in 11q13 by genetic linkage analysis. Since this region was found to be refractory to cloning in YAC (yeast artificial chromosome)-based vectors, a P1 artificial chromosome (PAC) contig was assembled. Gridded PAC libraries representing a 16-fold genome equivalent were screened by hybridization using PCR products representing STSs derived from YAC end sequences, markers binned to 11q13, and PAC-derived insert ends. A highly marker dense approximately 1.7-Mb PAC contig that encompassed the disease gene region was constructed, allowing us to order accurately the markers throughout the region and to provide the most precise estimate of its physical size. Using this contig, thus far we have mapped seven anonymous ESTs and five known genes into this region. This high-resolution physical map will facilitate the isolation of polymorphic markers for refinement of the disease gene region, as well as the identification of candidate genes by exon trapping, cDNA selection, and gene prediction from PAC-derived genomic sequence.

Chromosome Mapping↗
PubMed1997

Symptom resolution, tumor control, and side effects following postoperative radiotherapy for pituitary macroadenomas.

This study reports the outcome of 70 patients who were treated by a consistent treatment plan of surgery and postoperative radiotherapy (RT) for pituitary macroadenomas in the modern era [computed tomographic scan or magnetic resonance imaging (MRI), dopamine agonist therapy (DA) added as indicated, and immunohistochemical staining]. Sixty-two patients underwent transsphenoidal surgery (vs. transcranial surgery) and 61 received 45-Gy/25 fractions postoperatively (vs. other dose fractionation schemes). Twenty-four patients received DA for prolactin-secreting tumors. With a median follow-up of 8 years (range 2-15), 68 patients have experienced continuous control of their tumors. Most symptoms related to mass effect abated, while physiologic symptoms such as amenorrhea from markedly elevated prolactin levels tended to persist. Treatment-induced hypopituitarism occurred in 42% of the patients at risk. No patients in this series have died as a result of their pituitary tumor. No gross neuropsychologic dysfunction after treatment has been noted. While it is possible at this time with serial MRI to withhold postoperative RT and observe some patients who have had a "gross total" resection of a macroadenoma, the therapeutic ratio for surgery and adjuvant radiotherapy for patients with nonfunctional tumors as well as select patients with secretory macroadenomas is favorable.

Adenoma↗
PubMed1997

Construction of a transcription map around the gene for ataxia telangiectasia: identification of at least four novel genes.

We have constructed YAC, PAC, and cosmid contigs in the ataxia-telangiectasia gene region and used the assembled clones to isolate expressed sequences by exon trapping and hybridization selection. In the interval between D11S1819 and D11S2029, exons and cDNAs for potentially 13 different genes were identified. Three of these genes, F37, K28, and 6.82, are large novel genes expressed in a variety of different tissues. K28 shows sequence homology to the Rab GTP binding protein family and gene 6.82 homology to the rabbit vasopressin activated calcium mobilizing receptor, while gene F37 has no homology to any known sequence in the database. Three further clones, exon 6.41 and cDNAs K22 and E74, from the interval between D11S1819 and D11S2029, appear to be expressed endogenous retrovirus sequences. The fourth large novel genes, E14, together with two further possible novel genes, E13 and E3, was identified from exons and cDNAs in the more telomeric 300-kb interval between markers D11S2029 and D11S2179. These are in addition to the genes for mitochondrial acetoacetyl-CoA-acetyltransferase (ACAT) and the ATM gene in the same region. Genes E3, E13, and E14 do not show homology to any known genes. K28, 6.82, ACAT, and ATM all appear to have the same transcriptional orientation toward the telomere.

Acetyl-CoA C-Acetyltransferase↗
PubMed1997

Identification and analysis of expression of human VACM-1, a cullin gene family member located on chromosome 11q22-23.

We have localized the human homolog of the rabbit vasopressin-activated calcium-mobilizing receptor VACM-1 to a region close to the gene for ataxia telangiectasia ATM on chromosome 11q22-23. We have determined the complete amino acid sequence of the human Hs-VACM-1 protein, which is 780 amino acids long. The human and rabbit sequences are highly conserved, differing at only seven amino acids. Northern analysis of the human gene showed expression in a wide range of human tissues. The Hs-VACM-1 gene has homology with the Caenorhabditis elegans gene Ce-cul-5, a member of a family of cullin genes that are involved in cell cycle regulation and that might, when mutated, contribute to tumor progression.

Amino Acid Sequence↗
PubMed1997

Intraoperative monitoring of spinal cord function using motor evoked potentials via transcutaneous epidural electrode during anterior cervical spinal surgery.

Because false-positive results are not infrequent when monitoring somatosensory evoked potentials during surgery, monitoring of motor evoked potentials (MEPs) has been proposed and successfully used during the removal of spinal cord tumors. However, this often requires direct visual placement of an epidural electrode after a laminectomy. We evaluated the use of MEPs, recorded via a transcutaneously placed epidural electrode, to monitor motor pathway functional integrity during surgery on the anterior cervical spine. Sixteen patients underwent anterior cervical vertebral decompression and fusion for cervical myelopathy and/or radiculopathy. Before surgery, an epidural monitoring electrode was placed transcutaneously at the midthoracic level and was used to record MEPs after transcranial cortical electrical stimulation. Electrode placement was successful in all patients but one, and satisfactory baseline spinal MEPs were obtained except for one patient who had cerebral palsy with significant motor dysfunction. Patients showed no significant changes in spinal MEPs during surgery, and all had baseline or better motor function postoperatively. None had complications from epidural electrode placement or electrical stimulation. We conclude that motor pathways can be monitored safely during anterior cervical spinal surgery using spinal MEPs recorded via a transcutaneously placed epidural electrode, that MEP preservation during surgery correlates with good postoperative motor function, and that cerebral palsy patients may possess too few functional motor fibers to allow MEP recording.

Adolescent↗
PubMed1996

Perioperative complications of transseptosphenoidal excision for pituitary adenomas.

Although complications of transseptosphenoidal (TSS) pituitary surgery have been discussed in the literature, there has not been an analysis of complication rates related to clinical features and the nature of the tumor. A retrospective review of 366 TSS procedures (354 patients) for excision of pituitary adenomas evaluated the incidence and management of perioperative complications. The mortality rate was 0.82%. The most frequently encountered complications were transient diabetes insipidus (8.74%) and cerebrospinal fluid (CSF) rhinorrhea (4.10%). Other complications included exacerbation of visual acuity and visual field defects, hemorrhage, hydrocephalus, and meningitis. The factors evaluated were gender, age, tumor size, hormone secretory status, and any history of prior pituitary surgery.There was a significantly higher incidence of transient diabetes insipidus in patients with hormone-secreting tumors. Minor and total complication rates were significantly increased in microadenomas, hormone-secreting tumors, in female patients, and in patients less than 60 years of age reflecting the increased incidence of transient diabetes insipidus in young female patients with hormone-secreting tumors. Observed intraoperative CSF leaks predisposed to postoperative CSF rhinorrhea. There were no identifiable risk factors for major complications.

Journal Article↗
PubMed1996

A gene transcribed from the bidirectional ATM promoter coding for a serine rich protein: amino acid sequence, structure and expression studies.

In an earlier report we showed that the 5' end of the gene for ataxia telangiectasia ATM is within 700 bp of the 5' end of a novel gene E14, and suggested that the CpG island that separates these genes functions as a bidirectional promoter. We have now determined the complete amino acid sequence of the E14 protein, defined the exon/intron structure of the gene and estimate that the complete gene is more than 55 kb in length. The E14 gene appears to be a housekeeping gene that is expressed in all tissues, including all parts of the brain. The E14/ATM promoter organisation is conserved in man, monkey and mouse, although the mouse promoter is more compact and appears to lack two of the four putative Sp1 boxes found in the human promoter. Reporter gene constructs showed that the human and mouse E14/ATM promoters were indeed bidirectional, that the ATM side of the human promoter was three times stronger than the E14 side, and that the mouse promoter (in human cells) directed transcription with equal efficiency in both directions, but at a lower level than the human promoter. Analysis of a small number of A-T patients for mutations in the promoter region or the E14 coding sequence did not provide evidence to suggest that E14 contributes to the A-T phenotype.

3T3 Cells↗
PubMed1996

Quantitative three-dimensional anatomy of the subaxial cervical spine: implication for anterior spinal surgery.

Knowledge of the quantitative anatomy of the subaxial cervical vertebrae is essential to safely perform anterior cervical surgery and to ensure adequate decompression of neural structures. In spite of this, little has been published in the neurosurgical literature regarding the spatial relationship of the lower cervical vertebrae and the implications of this anatomy for anterior cervical surgery. We report the three-dimensional analysis of the mid- and lower cervical spine in 10 cadaver specimens for 50 disarticulated vertebrae and discuss the relevance of this analysis to surgery in this region. Measurements were made using real-time video analysis of images transferred from a Zeiss microscope equipped with an image splitter and a Sony charge-coupled device camera. Images were then transferred to an IBM personal computer-based image analysis system. Analysis of variance was used to test for significant differences among the C3-C7 vertebral measurements. Important relationships of the vertebral artery to the anteroposterior diameter of the vertebral bodies and its variations from C3 to C7 are discussed. The vertebral artery migrates posteriorly to anteriorly from C3 to C6 and posteriorly again at C7; the implications of these variations are discussed for decompression of the neural foramen. Another finding showing that the inter-Luschka distance increases from C3 to C7 is important for adequate lateral decompression in anterior cervical spinal surgery. The pedicle to the Luschka joint was measured at the different levels; the pedicle is lateral to the Luschka joint from C3 to C6 and medial to the joint at C7. This variation explains the lack of root decompression at some cervical levels, even when decompression extends to the Luschka joint bilaterally. We also report the measurements of the vertebral bodies and the spinal canal and compare the results with other published data. We think these measurements provide guidelines for operating on the anterior cervical spine, facilitate adequate decompression of the spinal cord and neural foramen, and increase the margin of safety of the surgeon.

Anthropometry↗
PubMed1995

Modern management of spinal tuberculosis.

The resurgence of pulmonary tuberculosis in the United States has been paralleled by a concomitant rise in tuberculosis of the spine (Pott's disease). The appearance of drug-resistant strains of tuberculosis, infection in large numbers of immunocompromised hosts, newer imaging modalities, and the development of more effective spinal reconstruction techniques have raised important issues regarding the management of Pott's disease. In spite of this, there has been little published recently on the modern management of Pott's disease in developed countries. We report our experience with the management of 20 patients with Pott's disease in the past 5 years, 16 of whom were admitted during the last 18 months of this retrospective study. The mean patient age was 49 years. Sixteen (80%) were men. Nineteen (95%) had a positive tuberculin skin test, and 13 (65%) had pulmonary tuberculosis. Symptoms consisted of spinal pain, weakness, sensory complaints, and flank mass in order of decreasing frequency. Ten patients were neurologically intact; the remainder had motor deficits of variable severity. The thoracic spine was involved in 13 patients, the lumbar spine was involved in 4, the cervical spine was involved in 2, and the thoracolumbar spine was involved in 1. Spinal deformity was present in 11 patients, spinal epidural compression was present in 13, and a paraspinal mass was present in 18. Operative indications included motor deficits, spinal deformity, nondiagnostic computer tomographic-guided needle biopsy, and noncompliance with, or lack of, response to medical therapy. Eleven patients underwent operations. Six patients had vertebrectomy and bone grafting with posterior instrumentation when indicated; three had laminectomy, debridement, and abscess drainage; one had laminectomy and posterior instrumentation; and one had paraspinal abscess drainage. Two patients have died; the remainder have been monitored for at least 1 year and are neurologically improved or normal without residual infection. The average angulation decreased from 31 to 24 degrees by the follow-up examination. In selected patients, early operative treatment with instrumentation, when indicated, minimizes neurological deterioration and spinal deformity, allows early ambulation, and results in excellent neurological outcome.

Adult↗
PubMed1994

A physical map across chromosome 11q22-q23 containing the major locus for ataxia telangiectasia.

We have constructed a long-range physical map for 12 markers, including genes for GRIA4, IL1BC, and ACAT, across 9 Mb of chromosome 11q22-q23 in the region of the major locus for ataxia-telangiectasia (A-T). The markers fall into proximal and distal groups with respect to the centromere. We have linked the proximal and distal groups by hybridization to a 2.7-Mb NotI fragment and a 4.6-Mb MluI fragment. The following locus order was obtained: centromere-CJ52.75-J12.1C2-Y11B11R-IL1BC-+ ++hbcDNA-GRIA4-CJ52.3-Y11B29L-ACAT- CJ52.193-J12.8-Y11B06R-telomere. We show that hbcDNA/GRIA4 and CJ52.3 are very closely linked to each end, respectively, of the 2.7-Mb NotI fragment, thereby fixing the position of the complete contig. Our results indicate that the gene for A-T is flanked by the markers GRIA4 and J12.8, which are no more than 3 Mb apart, on a 4.6-Mb MluI fragment. The physical map allows rapid positioning of markers, and this will facilitate the construction of a YAC contig across the region.

Ataxia Telangiectasia↗
PubMed1994

Posterior plates in the management of cervical instability: long-term results in 44 patients.

Although posterior plates are increasingly used to manage cervical spinal instability, long-term follow-up evaluation of patients with a critical analysis of efficacy and complications has not been reported. The authors have retrospectively analyzed the outcome in 44 consecutive patients (37 males and seven females, age range 16 to 80 years) treated with posterior cervical plates. The indications for instrumentation were instability due to trauma in 42 cases, tumor in one, and infection in one. In four patients the follow-up period was limited to 3, 5, 11, and 16 months. Two patients died of chronic medical problems 4 and 9 months after treatment. The remaining 38 patients were followed from 2 to 6 years (mean 46 months). One motion segment was stabilized in 23 patients using two-hole plates; two motion segments were stabilized in the other 21 patients using three-hole plates. In the majority of patients (37 cases), supplemental bone grafting was not used. Patients were immobilized postoperatively in a Philadelphia collar. Solid arthrodesis was achieved in 39 (93%) of 42 patients. Three patients required revision of the cervical plating: in one patient with a C-5 burst fracture, two-hole plates were applied at C5-6 and progressive kyphosis mandated anterior fusion; the second patient required posterior wiring due to screw pull-out resulting from a technical error in screw insertion; the third patient, who refused to wear an orthosis postoperatively, also developed screw pull-out. In two patients who went on to spinal fusion, there was an increase in sagittal kyphosis (6 degrees and 8 degrees) without clinical sequelae. Screw loosening was noted in five patients, involving eight (3.8%) of the 210 lateral mass screws; this complication resulted in instrumentation failure or increased kyphosis in three cases. There were two superficial infections. This analysis indicates that posterior cervical plating is highly effective; at long-term follow-up review the cervical spine was successfully stabilized in 93% of cases. Plate failure was related to faulty screw placement, failure to include sufficient motion segments, and noncompliance with postoperative orthoses. Halo vest immobilization was unnecessary and supplemental bone grafting was generally not required for recent trauma.

Adolescent↗
PubMed1993

A systematic approach to spinal reconstruction after anterior decompression for neoplastic disease of the thoracic and lumbar spine.

The anterior approach to the thoracic and lumbar spine for neoplastic disease is now a well-accepted procedure, with results, for the most part, superior to those achieved with laminectomy. However, the specific indications for anterior decompression and the selection of reconstruction techniques based on the location and extent of bony destruction have received surprisingly little attention. The authors report their experience with the operative management of 33 patients with benign and malignant tumors of the thoracic and lumbar spine, using the anterior transthoracic or retroperitoneal approach. The role of stabilization and the relative indications for anterior or posterior instrumentation are emphasized. The mean age of patients was 58 years. Twenty-three patients were male. Five patients had benign tumors, and the remainder had a variety of metastatic lesions. Twenty-nine patients had lower extremity motor deficits, although 25 were ambulatory preoperatively. Thirty-seven noncontiguous resections were performed in 33 patients. In 13 patients, the resected vertebral body was replaced with acrylic or bone without instrumentation; in 18, the acrylic was supplemented with anterior instrumentation; and in 6, both anterior and posterior instrumentation were used. Above T11, vertebral reconstruction techniques were used to restore stability after decompression. Between T11 and L4, anterior instrumentation was used to supplement vertebral reconstruction in all patients. Supplemental posterior instrumentation was used for three-column involvement. Motor function was stabilized or improved in 94% of patients, and 88% of patients were ambulatory postoperatively. Of 28 patients with malignant disease, 23 died after a mean survival of 10.2 months (range, 2-51 mo) and 5 are alive a mean of 34.4 months since their operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗