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Biomedical subjects

P A Robinson

Publications and source records attributed to P A Robinson.

At least 19 recordsLinked to original sources
PubMed1999

The ubiquitin-conjugating enzymes UbcH7 and UbcH8 interact with RING finger/IBR motif-containing domains of HHARI and H7-AP1.

Ubiquitinylation of proteins appears to be mediated by the specific interplay between ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s). However, cognate E3s and/or substrate proteins have been identified for only a few E2s. To identify proteins that can interact with the human E2 UbcH7, a yeast two-hybrid screen was performed. Two proteins were identified and termed human homologue of Drosophila ariadne (HHARI) and UbcH7-associated protein (H7-AP1). Both proteins, which are widely expressed, are characterized by the presence of RING finger and in between RING fingers (IBR) domains. No other overt structural similarity was observed between the two proteins. In vitro binding studies revealed that an N-terminal RING finger motif (HHARI) and the IBR domain (HHARI and H7-AP1) are involved in the interaction of these proteins with UbcH7. Furthermore, binding of these two proteins to UbcH7 is specific insofar that both HHARI and H7-AP1 can bind to the closely related E2, UbcH8, but not to the unrelated E2s UbcH5 and UbcH1. Although it is not clear at present whether HHARI and H7-AP1 serve, for instance, as substrates for UbcH7 or represent proteins with E3 activity, our data suggests that a subset of RING finger/IBR proteins are functionally linked to the ubiquitin/proteasome pathway.

Amino Acid Sequence↗
PubMed1999

Characterization of the mouse ubiquitin-conjugating enzyme gene UbcM4.

The ubiquitination pathway targets not only normal (short-lived) intracellular eukaryotic proteins for degradation when appropriate, but also serves to eliminate mutant/misfolded proteins from the cell. An understanding of the molecular basis of the interaction between the ubiquitin-conjugating enzymes (E2s), ubiquitin protein ligases (E3s), and target proteins is essential to explain the process in normal cellular function and in disease. UbcM4 is the mouse ortholog of the human E2, UbcH7, which can participate in the in vitro degradation of many proteins including p53. We describe the characterization of the mouse UbcM4 gene and the identification of a UbcM4 pseudogene. Four UbcM4 transcripts of approximately 0.7, 1.5, 2.1, and 2.6 kb, observed on Northern blots, are differentiated by their utilization of alternative UbcM4 polyadenylation sites. A single alternative splice variant cDNA, termed UbcM4Deltaex2, was also identified. The polypeptide encoded by UbcM4Deltaex2 is incapable of forming an ubiquitin-thioester in contrast to UbcM4, despite retaining the key cysteine residue essential for ubiquitin thioester formation and the active site consensus sequence that defines the ubiquitin-conjugating enzyme class. These observations are of particular relevance for analysis of UbcM4 function in vivo as our studies indicate that the targeted deletion of the coding exon absent in UbcM4Deltaex2 would produce an inactive UbcM4 protein and presents an alternative to disruption of its transcriptional initiation site/promoter region. Furthermore, it suggests that a similar strategy may be applicable to disrupt the function of other ubiquitin-conjugating enzymes in vivo.

Alternative Splicing↗
PubMed1999

A novel presenilin-2 splice variant in human Alzheimer's disease brain tissue.

Mutations in the presenilin-1 (PS-1) and presenilin-2 (PS-2) genes account for the majority of cases of early-onset familial Alzheimer's disease (AD). Alternative splicing forms of the PS-1 and PS-2 gene products have previously been reported in fibroblast and brain tissue from both familial and sporadic AD patients, as well as from normal tissues and cell lines. We demonstrate here unusual alternative splicing of the PS-2 gene that leads to the generation of mRNA lacking exon 5 in human brain tissue. This product was more frequently detected in brain tissue from sporadic AD patients (70.0%; 21 of 30) than from normal age-matched controls (17.6%; three of 17). In cultured neuroblastoma cells, this splice variant was generated in hypoxia but not under other forms of cellular stress. Hypoxia-mediated induction of this splice variant was blocked by pretreatment of neuroblastoma cells with the protein synthesis inhibitor cycloheximide or antioxidants such as N-acetylcysteine and diphenyl iodonium, suggesting that hypoxia-mediated oxidant stress might, at least in part, underlie the alternative splicing of PS-2 mRNA through de novo protein synthesis. Furthermore, the stable transfectants of this splice variant produced the N-terminal part of PS-2 protein (15 kDa) and were more susceptible to cellular stresses than control transfectants. These results suggest the possibility that altered presenilin gene products in stress conditions may also participate in the pathogenesis of AD.

Aged↗
PubMed1999

Early mycological treatment failure in AIDS-associated cryptococcal meningitis.

Cryptococcal meningitis causes significant morbidity and mortality in persons with AIDS. Of 236 AIDS patients treated with amphotericin B plus flucytosine, 29 (12%) died within 2 weeks and 62 (26%) died before 10 weeks. Just 129 (55%) of 236 patients were alive with negative cerebrospinal fluid (CSF) cultures at 10 weeks. Multivariate analyses identified that titer of cryptococcal antigen in CSF, serum albumin level, and CD4 cell count, together with dose of amphotericin B, had the strongest joint association with failure to achieve negative CSF cultures by day 14. Among patients with similar CSF cryptococcal antigen titers, CD4 cell counts, and serum albumin levels, the odds of failure at week 10 for those without negative CSF cultures by day 14 was five times that for those with negative CSF cultures by day 14 (odds ratio, 5.0; 95% confidence interval, 2.2-10.9). Prognosis is dismal for patients with AIDS-related cryptococcal meningitis. Multivariate analyses identified three components that, along with initial treatment, have the strongest joint association with early outcome. Clearly, more effective initial therapy and patient management strategies that address immune function and nutritional status are needed to improve outcomes of this disease.

AIDS-Related Opportunistic Infections↗
PubMed1999

Analysis of regression of postoperative carotid stenosis from prospective randomized trial of carotid endarterectomy comparing primary closure versus patching.

BACKGROUND AND PURPOSE: Recurrent stenosis after carotid endarterectomy (CEA) has been reported to vary between a few percent and 30%. Regression of recurrent stenosis has been reported sporadically in the literature, but studies analyzing the factors affecting regression are lacking. This study analyzed factors affecting the regression of postoperative stenosis from a prospective randomized trial of CEA comparing primary closure (PC) versus patching. PATIENT POPULATION AND METHODS: Three hundred ninety-nine CEAs were randomized into three groups: 135 PCs, 135 polytetrafluoroethylene patch closures (PTFE), and 130 vein patch closures (VPC). Postoperative duplex ultrasounds were done at 1, 6, and 12 months, and then yearly. The subgroup of these CEAs that exhibited postoperative stenosis was followed for possible regression of the stenosis. Analyses of various risk factors were examined for possible association with regression of recurrent stenosis. Mean follow-up was 46 months. RESULTS: Of 105 postoperative stenoses, regression was noted in 6/64 (9%) in PC, 6/13 (46%) in PTFE, and 10/28 (36%) in VPC. Overall, 22 recurrent stenoses regressed; 19 regressed to normal and 3 regressed from 50% to 80% stenosis to 20% to <50% stenosis. The mean time to regression was 383 days. Regression was more common in patching than PC. Both VPC and PTFE had significantly more regression than PC. When stenoses of 50% to 80% were analyzed, patching had more regression than PC. None of the recurrent stenoses > or = 80% regressed. There was no association between regression and other factors, including gender, hypertension, diabetes mellitus, coronary artery disease, smoking, internal carotid artery diameter, hyperlipidemia, hypercholesterolemia, or aspirin intake. CONCLUSIONS: Regression of recurrent stenosis was associated more strongly with patching than with PC. There was no association between regression and other factors.

Carotid Stenosis↗
PubMed1999

Signal recognition particle receptor (SRPR) is downregulated in a rat model of cyclosporin A-induced gingival overgrowth.

Differential display is a powerful technique which can be used to identify those genes whose expression is altered between two or more tissues under investigation. We have applied differential display to a rat model of cyclosporin A-induced gingival overgrowth (CIGO) to identify genes which are differentially expressed as a result of drug treatment. Ten weanling Wistar rats were fed with a pelleted diet containing cyclosporin A (CsA) at 120 mg/kg for 10 d and then 200 mg/kg for a further 30 d prior to culling. Experimental rats were compared with 10 age/sex-matched rats on a control diet. Significant evidence of overgrowth was observed in the interdental papilla between the mandibular first and second molar teeth in the CsA group. Differential display was performed on total cellular RNA extracted from the mandibular buccal gingiva. A cDNA product was isolated which was underexpressed in the overgrowth tissue and demonstrated a 95% sequence homology to the human signal recognition particle receptor (Human Docking Protein). Preliminary studies indicate that this gene is also underexpressed in human CIGO tissue. The method of approach and the potential implications of our findings are discussed.

Animals↗
PubMed1999

Prospective randomized trial of bilateral carotid endarterectomies: primary closure versus patching.

BACKGROUND AND PURPOSE: Although several studies have compared the results of carotid endarterectomy (CEA) with primary closure (PC) versus patch closure, none have compared the outcome of bilateral CEAs with patch versus PC performed on the same patient. This prospective randomized study compares the clinical outcome and incidence of recurrent stenosis (>/=80%) for CEA with PC versus patch closure in patients with bilateral CEAs. METHODS: This study includes 74 patients with bilateral CEAs with PC on one side and patching on the other. Patients were randomized to sequential operative treatment of either patching/PC or PC/patching. Postoperative duplex ultrasounds and clinical follow-up were done at 1, 6, and 12 months and every year thereafter. A Kaplan-Meier analysis was used to estimate the risk of significant restenosis (>/=80%). RESULTS: Demographic characteristics and the mean operative diameter of the internal carotid artery were similar for both PC and patching. The mean follow-up was 29 months (range, 6 to 65 months). The incidence of ipsilateral stroke was 4% for PC versus 0% for patching. PC had a significantly higher incidence of neurological complications (transient ischemic attacks and stroke combined) than patching (12% versus 1%; P=0.02). Operative mortality was 0%. PC had a higher incidence of recurrent stenosis (22% versus 1%; P<0.003) and total internal carotid artery occlusion (8% versus 0%; P=0.04) than patching. Restenoses necessitating a repeated CEA were also higher for PC (14%) than for patching (1%; P=0.01). The Kaplan-Meier analysis showed that patching had a significantly better cumulative patency rate than PC (P<0.01). This analysis also showed that freedom from recurrent stenosis at 24 months was 75% for PC and 98% for patching. CONCLUSIONS: Patch closure is less likely than PC to cause ipsilateral stroke, transient ischemic attacks, and recurrent carotid stenosis. The higher rate of unilateral recurrent stenosis may suggest that local factors play a more significant role than systemic factors in the etiology of recurrent carotid stenosis.

Carotid Arteries↗
PubMed1999

The role of carotid duplex ultrasound in evaluating plaque morphology: potential use in selecting patients for carotid stenting.

PURPOSE: To study the role of duplex ultrasonography in evaluating plaque morphology and its correlation to neurological symptoms and cerebral infarctions on computed tomographic scans. METHODS: The hospital records of 181 patients (107 males; average age 66 years, range 41 to 89) with > 50% carotid stenosis (29 bilateral lesions) who had undergone duplex ultrasonography, carotid arteriography, and cerebral computed tomography were studied retrospectively. Of 210 duplex examinations, 139 were appropriate for morphological analysis of surface characteristics and echogenicity. RESULTS: Over half of the plaques examined had irregular surfaces (81, 58%) and displayed mixed (i.e., heterogeneous) echogenic patterns (74, 53%). Irregular (68 of 81, 84%) and heterogeneous (65 of 74, 88%) plaques were associated with ipsilateral neurological symptoms (p < 0.0001). Similarly, 44 (54%) of 81 irregular plaques and 42 (57%) of 74 heterogeneous plaques were found in patients with cerebral infarctions in the carotid territory (p < 0.0001). CONCLUSIONS: Heterogeneous and/or irregular plaques were more often associated with both neurological symptoms and infarctions than smooth or homogeneous plaques. These findings may have implications in patient selection for endoluminal therapy.

Adult↗
PubMed1999

Prospective controlled study of polytetrafluoroethylene versus saphenous vein in claudicant patients with bilateral above knee femoropopliteal bypasses.

BACKGROUND: Although several studies have compared the patency rates of polytetrafluoroethylene (PTFE) and saphenous vein grafts (SVG) for the above knee location, none have compared the 2 grafts when implanted in the same patient with claudication who needs bilateral above knee femoropopliteal bypasses. METHODS: Forty-three patients (86 limbs) with bilateral disabling claudication who had superficial femoral artery occlusion and above knee reconstitution with 2- to 3-vessel runoff were analyzed. Patients were treated on one side with PTFE and on the other side with SVG. They were sequentially assigned to PTFE-SVG alternating with SVG-PTFE. All patients were followed using duplex ultrasound and ankle/brachial indexes at 1 month and every 6 months thereafer. RESULTS: The perioperative complication rates were 5% for PTFE and 12% for SVG. There was no operative death or perioperative amputation for either procedure. The Kaplan-Meier estimate of primary, assisted primary, and secondary patency rates at 72 months were 68%, 68%, and 77% for PTFE and 76%, 83%, and 85% for SVG. There were no statistically significant differences between primary and secondary patency rates for both grafts; however; the assisted primary patency rates were higher for SVG (P < .05). The crude limb salvage rate at 72 months was 98% for PTFE and 98% for SVG. There were no risk factors identified that had an impact on graft patency. CONCLUSIONS: PTFE and SVG for above knee bypasses have comparable patency and limb salvage rates in claudicant patients with bilateral superficial femoral artery occlusion and 2- to 3-vessel runoff This may justify the use of PTFE for above knee locations in these selected patients.

Aged↗
PubMed1998

Fine-mapping, genomic organization, and transcript analysis of the human ubiquitin-conjugating enzyme gene UBE2L3.

The human UBE2L3 gene encodes the ubiquitin-conjugating enzyme UbcH7, demonstrated to participate in the ubiquitination of p53, c-Fos, and NF-kappaB in vitro. We report the fine-mapping of this four-exon gene to chromosome 22q11.2. We have constructed a comprehensive genomic clone contig across this gene, demonstrating that the gene lies adjacent to the microsatellite marker D22S446 and spans approximately 57 kb. Four mRNA species are transcribed from this gene, differing in the length of their 3' UTR. Sequence comparison of the UBE2L3 cDNA with its murine homologue reveals a remarkably high degree of sequence conservation within the 3'UTR.

Base Sequence↗
PubMed1998

Proposed new duplex classification for threshold stenoses used in various symptomatic and asymptomatic carotid endarterectomy trials.

Current duplex ultrasound criteria for internal carotid artery (ICA) stenosis (1%-15%, 16%-49%, 50%-69%, 70%-99%) may not be applicable to threshold stenoses used in symptomatic (North American Symptomatic Carotid Endarterectomy Trial [NASCET], Veterans' Administration [VA]) and asymptomatic (Asymptomatic Carotid Atherosclerosis Study, VA) carotid endarterectomy (CEA) trials. This, along with increasing reports advocating CEA based on duplex results alone, prompted us to identify (1) new velocity criteria consistent with threshold stenoses used by these trials, and (2) velocity criteria with a high positive predictive value (PPV) (> 95%) and accuracy for detecting > or = 60% and > or = 70% ICA stenoses. This is the first study to propose criteria which can be used for all current CEA trials. The color duplex ultrasound (CDU) and arteriogram results of 462 ICAs were analyzed in blind fashion. Angiographic stenosis was calculated as in NASCET. Three velocity criteria (peak systolic velocity [PSV] of the ICA, end diastolic velocity [EDV] of the ICA, and the ratio of the PSV of the ICA/common carotid artery) were recorded and subjected to receiver operator characteristic curves (ROC) analysis to determine optimum criteria for identifying ICA stenoses of > or = 30%, > or = 50%, > or = 60%, and > or = 70%-99%. For > or = 30% stenosis (st): PSV > or = 120 cm/sec had an overall accuracy (OA) of 87%, sensitivity (sen.) of 93%, specificity (spec.) of 67%, PPV of 90%, and negative predictive value (NPV) of 77%; for > or = 50% st: PSV > or = 140 cm/sec had an OA of 93%, sen. of 92%, spec. of 95%, PPV of 97%, and NPV of 89%; for > or = 60% st: PSV > or = 150 cm/sec and an EDV of > or = 65 had an OA of 90%, sen. of 82%, spec. of 97%, PPV of 96%, and NPV of 86%; for > or = 70%-99% st: PSV > or = 150 cm/sec and an EDV of > or = 90 had an OA of 92%, sen. of 85%, spec. of 95%, PPV of 91%, and NPV of 92%. An ICA-PSV and EDV of 150, 65, and 150, 110 had the best PPV (> or = 95%) in detecting > or = 60% and > or = 70% st, respectively. When these new criteria are used, CDU can accurately detect threshold stenoses used by various CEA trials. Selected velocities with a high PPV (> 95%) may be used as the sole preoperative imaging.

Adult↗
PubMed1998

Etiology of peripheral arterial thromboembolism in young patients.

BACKGROUND: No prior studies have explored the etiology of peripheral arterial thromboembolic events (PATE) in younger patients. Therefore, we analyzed the sources of these events in patients <50 years of age over a recent 10-year period. Diagnostic and work-up strategies will be proposed based on the presence of cardiac or atherosclerotic risk factors. PATIENTS AND METHODS: The sources of emboli were classified as (1) conventional (cardiac or arterioarterial), (2) unconventional, or (3) unknown. A statistical analysis of risk factors that, if absent, would suggest an unconventional cause was performed. Risk factors included those for cardiac and atherosclerotic disease: coronary artery disease (CAD), valvular disease, smoking, arrhythmia, hypertension, or diabetes mellitus. RESULTS: Overall, 51 patients were identified. Twenty-nine patients (57%) had unconventional causes (8 paradoxical emboli, 4 possible paradoxical emboli, 12 hypercoagulable states, 3 white clot syndromes, and 2 cervical ribs), 17 (33%) had conventional causes, and 5 (10%) were unknown. When the number of cardiac risk factors was < or =1, excluding smoking, the probability of a conventional source was zero, in contrast to 100% if the number of risk factors was >1. When the following risk factors were absent, there were significantly more unconventional than conventional sources of emboli (P < 0.001): smoking (100% versus 0%), CAD (93% versus 7%), arrhythmias (83% versus 17%), hypertension (93% versus 7%), and diabetes mellitus (81% versus 19%). Patients with a conventional source were significantly older (44 versus 38 years). CONCLUSIONS: The "unconventional" causes of PATE were responsible for a higher percentage of cases in young patients. An analysis of the number of risk factors was useful in predicting which patients suffered embolic events from conventional sources, with the critical number being >1 (excluding smoking). Therefore, when younger patients present with PATE, and are found to have < or =1 identifiable cardiac risk factor, their work-up should be directed toward the unconventional sources first.

Adult↗
PubMed1998

A prospective controlled study of the efficacy of short-term anticoagulation therapy in patients with deep vein thrombosis of the lower extremity.

PURPOSE: The long-term risk for recurrent deep venous thrombosis (DVT) and the incidence of post-thrombotic syndrome (PTS) after long-term anticoagulation (LTA) therapy have been widely debated. In this study, we compare the results of short-term anticoagulation therapy versus conventional LTA therapy in patients with DVT of the lower extremity. METHODS: Baseline assessments of DVT symptoms and risk factors were recorded in 105 patients. Diagnosis was made using duplex ultrasound/venography. Patients were sequentially assigned to 1 of the following treatment protocols: (A) conventional LTA therapy, which included initial intravenous standard heparin followed by warfarin on days 3 to 5 and was continued for 3 months for patients without pulmonary embolism (PE); or (B) short-term therapy, which included the same heparin therapy followed by warfarin on days 2 to 3 and was continued for 6 weeks only. Clinical and duplex ultrasound follow-up was done at 6 weeks, 3 and 6 months, and every 6 months thereafter. RESULTS: Risk factors, location of DVT, and mean age of the 2 groups were comparable. Mean follow-up was 59 months. There were 4 immediate major complications in patients of group A (4 of 54 [7%]; 2 PEs and 2 significant bleeds) and 3 in patients of group B (3 of 51 [6%]; 1 PE and 2 bleeds). On long-term follow-up, 18 of 43 (42%) patients in group A and 20 of 44 (46%) patients in group B had PTS. Similarly, 10 of 43 (23%) patients in group A and 9 of 44 (20%) patients in group B had 1 or more recurrent thromboembolic events (not statistically significant). A significant difference was demonstrated only in patients with cancer; LTA was favored in reducing recurrent DVT and PTS. Two other patients in group A had late significant complications secondary to warfarin (hemorrhage in 1 and coumadin necrosis in the other), with no complications in group B. The mean number of days of hospitalization were fewer for patients in group B (5 versus 8 days), which is mainly due to earlier initiation of warfarin therapy for group B. CONCLUSION: In this study of our local population, we observed that short-term anticoagulation therapy was as effective as LTA therapy and less costly for use in most patients. It may also carry less risk of long-term warfarin complications, such as bleeding or skin necrosis.

Anticoagulants↗
PubMed1998

Prospective randomized trial of carotid endarterectomy with primary closure and patch angioplasty with saphenous vein, jugular vein, and polytetrafluoroethylene: long-term follow-up.

PURPOSE: This study examines the long-term clinical outcome and the incidence of recurrent stenosis (> or = 50%) after carotid endarterectomy (CEA) with primary closure (PC) versus vein patch closure (VPC), saphenous (SVP), and jugular vein (JVP) and polytetrafluoroethylene patch closure (PTFE-P). METHODS: A total of 399 CEAs were randomized into the following groups: 135 PC, 134 PTFE-P, and 130 VPC (SVP alternating with JVP). Postoperative duplex ultrasound scans were performed at 1, 6, and 12 months and every year thereafter. The mean follow-up was 30 months with a range of 1 to 62 months, and demographic characteristics were similar in all groups. Kaplan-Meier analysis was used to estimate the risk of restenosis and the stroke-free survival. RESULTS: The incidence of ipsilateral stroke was 5% (seven of 135) for PC, 1% (one of 134) for PTFE-P, and 0% for VPC (PC vs VPC, p = 0.008; PC vs PTFE-P, p = 0.034). Seven strokes occurred in the perioperative period. All three groups had similar mortality rates. The cumulative stroke-free survival rate at 48 months was 82% for PC, 84% for PTFE-P, and 88% for VPC (p < 0.01 for PC vs PTFE-P or VPC). PC had a higher incidence of recurrent stenosis and occlusion (34%) than PTFE-P (2%) and VPC (9%) (SVP 9%, JVP 8%) (p < 0.001). PTFE-P had a lower recurrent stenosis rate than VPC (p < 0.045). Restenoses necessitating a redo CEA were also higher for PC (11%) than for PTFE-P (1%) and VPC (2%) (p < 0.001). Women with PC had a higher recurrent stenosis rate than men (46% vs 23%, p = 0.008). Kaplan-Meier analysis showed that freedom from recurrent stenosis at 48 months was 47% for PC, 84% for VPC, and 96% for PTFE-P (p < 0.001). The SVP and JVP results were comparable. The mean operative diameter of the internal carotid artery was similar in patients with or without restenosis. Significantly more late internal carotid artery dilatations occurred in the VPC group compared with the PC group. CONCLUSIONS: Patch closure (VPC or PTFE-P) is less likely than PC to cause perioperative stroke. Patching was also superior in lowering the incidence of late recurrent stenoses, especially in women.

Angioplasty↗
PubMed1998

The correlation of ultrasonic carotid plaque morphology and carotid plaque hemorrhage: clinical implications.

BACKGROUND: This study examined the importance of ultrasonic plaque morphology and its correlation to the presence of intraplaque hemorrhage and clinical implications. METHODS: One hundred fifty-two carotid plaques associated with > or = 50% internal carotid artery stenoses in 135 patients who had carotid endarterectomies were characterized ultrasonographically into irregular/ulcerative, smooth, heterogeneous, homogeneous, or not defined. All plaques were examined pathologically for the presence of intraplaque hemorrhage. RESULTS: The ultrasonic morphology of the plaques included 63 with surface irregularity (41%), 48 smooth (32%), 59 heterogeneous (39%), 52 homogeneous (34%), and 41 not defined (27%). Intraplaque hemorrhage was present in 57 of 63 (90%) irregular plaques and 53 of 59 (90%) heterogeneous plaques, in contrast to 13 of 48 (27%) smooth plaques and 17 of 52 (33%) homogeneous plaques (P < .001). Fifty-three of 63 (84%) irregular plaques and 47 of 59 (80%) heterogeneous plaques had transient ischemic attack (TIA)/stroke symptoms, in contrast to 9 of 48 (19%) for smooth plaques and 15 of 52 (29%) for homogeneous plaques (P < .001). CONCLUSIONS: Irregular and/or heterogeneous carotid plaques are more often associated with intraplaque hemorrhage and neurologic events. Therefore, ultrasonic plaque morphology may be helpful in selecting patients for carotid endarterectomy.

Adult↗
PubMed1998

An overview of the complexities and subtleties of immunohistochemistry.

Immunohistochemistry has the potential to be a powerful research tool. However, immunohistochemical studies are frequently undertaken without regard to the complexities and subtleties of these useful techniques. This review aims to address the problems and limitations that are often encountered, and the procedures that should be considered in both the planning and interpretation of immunohistochemical studies. Particular reference is made to the generation of functionally different protein isoforms from a single gene by alternative splicing and post-translational modifications, primary antibody selection, the effects of tissue manipulation such as fixation and antigen retrieval, the need for appropriate controls and interpretation of staining patterns.

Antibodies↗
PubMed1998

Fine mapping of 12 previously unassigned EST clones to individual YACs in the familial Alzheimer's disease (FAD) region of chromosome 14q24.3.

We have constructed an approximately 4-Mb YAC contig spanning the microsatellite markers D14S1028-D14S61 on chromosome 14q24.3 using oligonucleotide primers to microsatellite markers, ESTs and the genes PSEN1, FOS, TGFB3 and UBE2L1. This contig consists of 44 ICI YACs and 5 megaCEPH YACs. The data reported here should aid the final construction of an integrated map of chromosome 14 and allow the identification and accurate mapping of additional novel ESTs within this region.

Alzheimer Disease↗