Biomedical subjects

J P O'Connor

Publications and source records attributed to J P O'Connor.

At least 19 recordsLinked to original sources

PubMed2006

Retroperitoneal metastatic squamous cell carcinoma of the tonsil (with elevated beta human chorionic gonadotrophin): a misdiagnosis as extra-gonadal germ cell tumour.

Head and neck cancers usually spread first to the regional lymph nodes but rarely may metastasize to distant sites. Metastasis to distant lymph node groups is a rare event. Furthermore, delayed multiple metastases without local recurrence is relatively uncommon. A case of retroperitoneal metastasis from a squamous cell carcinoma of the tonsil, secreting beta human chorionic gonadotrophin (beta-hCG), is reported. A 58-year-old man had undergone a tonsillectomy and chemo-radiotherapy for squamous cell carcinoma of the left tonsil and 13 months later presented with non-specific abdominal pain. The serum beta-hCG levels were high and an abdominal ultrasound scan revealed hydronephrosis on the left side. A computed tomography scan demonstrated para-aortic retroperitoneal lymphadenopathy. The patient underwent an open lymph node biopsy. The initial pathological analysis was interpreted as extra-gonadal germ cell tumour and the patient received chemotherapy. A subsequent review was consistent with a metastatic squamous cell carcinoma of the tonsil, as immunohistochemical studies showed positive staining for epithelial membrane antigen and cytokeratins 5/6 but a negative reaction to placental alkaline phosphatase. Following this, the chemotherapy regimen was changed; however, a restaging scan demonstrated progression, and the patient died from aspiration pneumonia secondary to alcohol intoxication. To our knowledge, this is the first reported case of retroperitoneal metastasis from a squamous cell carcinoma of the tonsil, secreting beta-hCG and causing hydronephrosis. This case highlights the necessity of using clinical, histological, immunohistological and ultrastructural examination to establish precise diagnosis and to avoid inappropriate treatment.

Carcinoma, Squamous Cell↗

PubMed2001

The timing of neonatal discharge: An example of unwarranted variation?

UNLABELLED: Discharge from an intensive care nursery should be dependent on the infant's clinical and social condition and independent of the day of the week. OBJECTIVE: To evaluate admission and discharge dates of 5272 neonates cared for in 5 major metropolitan regions in the United States and managed by a national disease management company for the distribution of the day of the week. STUDY DESIGN: All infants discharged to home between July 1, 1996 and September 30, 1998 are included. Data are represented as a percentage of total discharges or admissions for each weekday assignment. Using the normal approximation to the multinomial distribution, we tested for proportional differences on each weekday. RESULTS: The data demonstrate that the timing of nursery discharge has an uneven distribution across the days of the week, with weekend (Saturday and Sunday) discharge rates that are significantly lower than weekday discharge rates. This uneven distribution exists in both the term and preterm subgroups as well. There is also an uneven distribution of births among the days of the week, with a pattern that reveals fewer weekend births than weekday births in the entire population studied, as well as in both the term and preterm subgroups. Normalizing these weekend discharges to the previous weekday could generate potential saving of $1 569 405 in charges for the total population and 627 days of hospitalization. The average length of stay of infants discharged on Mondays is longer than for those infants discharged on Saturday or Sunday. CONCLUSIONS: We speculate that changes in discharge planning could decrease the variation in day of discharge, shorten length of hospitalization, and potentially reduce cost.

Benchmarking↗

PubMed2000

Palivizumab for respiratory syncytial virus prophylaxis in high-risk infants: a cost-effectiveness analysis.

BACKGROUND: Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants. The cost-effectiveness of this therapy has not been evaluated from the provider's perspective using cost data. OBJECTIVES: The objectives of this study were to determine the cost per RSV infection episode avoided by using prophylactic palivizumab therapy in a high-risk infant population and to determine whether certain subgroups of infants derived greater benefit from prophylactic therapy. METHODS: A decision-analytic model simulating an RSV infection episode was developed to evaluate the cost-effectiveness of palivizumab prophylaxis from the perspective of the health care system (provider). Data to populate the model were gathered from the medical literature (identified through a MEDLINE search of studies on the incidence of RSV infection) and the IMpact-RSV clinical trial. Data included incidence of RSV infection and the associated health care resource use and costs. Costs to the provider were determined using a university-affiliated hospital cost-accounting system. Cost-effectiveness ratios were calculated over a range of RSV infection incidence rates in a control population. Sensitivity analyses were performed for the cost of palivizumab therapy, the cost of RSV-related hospitalization, and the number of emergency department, physician office, and home health care visits. For the subgroup analysis, infants were classified by gestational age (<32 and > or = 32 weeks) and stratified by severity of chronic lung disease. RESULTS: The cost per additional RSV infection episode avoided ranged from dollars 0 (cost savings) to dollars 39,591 for palivizumab prophylaxis costs of dollars 2500 and from dollars 2702 to dollars 79,706 for palivizumab prophylaxis costs of dollars 4500. The model was insensitive to changes in the number of emergency department, physician office, and home health care visits. The difference in RSV incidence between the treatment and control groups was greater among infants > or = 32 weeks' gestational age than among infants <32 weeks' gestational age. onclusions: The incremental cost-effectiveness of palivizumab compared with no prophylactic therapy was sensitive to changes in the incidence of RSV infection in control infants, the average cost of RSV hospitalization, and the cost of palivizumab. Clinicians may use this information along with additional factors to determine whether palivizumab is cost-effective in their clinical setting and geographic area.

Antibodies, Monoclonal↗

PubMed1999

Generalist versus specialist care for acute myocardial infarction.

Early studies conflict regarding improved patient outcomes with cardiologist-directed care for acute myocardial infarction (AMI). We sought to assess the magnitude and mechanism of the influence of physician specialty on inpatient mortality for AMI. Using data from the Pennsylvania Health Care Cost Containment Council and elsewhere, we developed age-stratified logistic regression models of inpatient mortality, utilizing a split sample strategy for model development and validation. Referral bias and physician caseload were explicitly addressed. We analyzed 30,351 admissions for AMI. In patients < 65 years old, the adjusted odds ratio (OR) for mortality with cardiologist care was 0.89 (95% confidence interval [CI] 0.640 to 1.24, p = 0.49) relative to generalist care. In patients > or = 65 years of age, the adjusted OR was 0.86 (95% CI 0.72 to 1.03, p = 0.10). Caseload was significantly higher among cardiologists and was inversely related to inpatient mortality. Mortality models with caseload but not physician designation or physician designation without caseload found each predictor statistically significant in the absence of the other (OR for cardiologist care 0.82, 95% CI 0.71 to 0.95, p = 0.007; OR for patients with low volume physicians relative to high volume 1.27, 95% CI 1.05 to 1.51, p = 0.014). Older patients of physicians with higher case loads had a lower risk adjusted inpatient mortality for AMI. This probably explains the trend toward better outcomes among patients of cardiologists rather than noncardiologists.

Age Factors↗

PubMed1999

Pta1, a component of yeast CF II, is required for both cleavage and poly(A) addition of mRNA precursor.

CF II, a factor required for cleavage of the 3' ends of mRNA precursor in Saccharomyces cerevisiae, has been shown to contain four polypeptides. The three largest subunits, Cft1/Yhh1, Cft2/Ydh1, and Brr5/Ysh1, are homologs of the three largest subunits of mammalian cleavage-polyadenylation specificity factor (CPSF), an activity needed for both cleavage and poly(A) addition. In this report, we show by protein sequencing and immunoreactivity that the fourth subunit of CF II is Pta1, an essential 90-kDa protein originally implicated in tRNA splicing. Yth1, the yeast homolog of the CPSF 30-kDa subunit, is not detected in this complex. Extracts prepared from pta1 mutant strains are impaired in the cleavage and the poly(A) addition of both GAL7 and CYC1 substrates and exhibit little processing activity even after prolonged incubation. However, activity is efficiently rescued by the addition of purified CF II to the defective extracts. Extract from a strain with a mutation in the CF IA subunit Rna14 also restored processing, but extract from a brr5-1 strain did not. The amounts of Pta1 and other CF II subunits are reduced in pta1 strains, suggesting that levels of the subunits may be coordinately regulated. Coimmunoprecipitation experiments indicate that the CF II in extract can be found in a stable complex containing Pap1, CF II, and the Fip1 and Yth1 subunits of polyadenylation factor I. While purified CF II does not appear to retain the association with these other factors, this larger complex may be the form recruited onto pre-mRNA in vivo. The involvement of Pta1 in both steps of mRNA 3'-end formation supports the conclusion that CF II is the functional homolog of CPSF.

Basic-Leucine Zipper Transcription Factors↗

PubMed1998

Zafirlukast improves asthma symptoms and quality of life in patients with moderate reversible airflow obstruction.

BACKGROUND: Previous trials demonstrated the effectiveness of the leukotriene receptor antagonist zafirlukast in patients with mild-to-moderate asthma. OBJECTIVES: We sought to assess the efficacy and safety of zafirlukast and its effect on patients' quality of life (QOL) during a 13-week, double-blind, placebo-controlled, multicenter trial in adults and adolescents with moderate reversible airflow obstruction. METHODS: Patients (age range, 12 to 68 years) with total daytime asthma symptoms scores of 10 or greater over 7 consecutive days (maximum, 21/wk), FEV1 45% or greater but less than or equal to 80% of predicted value (>/=6 hours after beta2 -agonist), and reversible airway disease were randomized to 20 mg zafirlukast twice daily (nZ = 231) or placebo twice daily (nP = 223). Efficacy was assessed from changes in daytime and nocturnal symptoms, beta2 -agonist use, nasal congestion score, and pulmonary function. QOL was evaluated with a disease-specific Asthma Quality of Life Questionnaire. Safety was determined from adverse event information and clinical laboratory test results. RESULTS: Zafirlukast was significantly (P <.001) more effective than placebo, with reductions from baseline in the daytime asthma symptoms score (-23%), nighttime awakenings with asthma (-19%), and beta2 -agonist use (-24%) and improvements from baseline in morning (+25 L/min) and evening (+18 L/min) peak expiratory flow rates. Compared with placebo, zafirlukast significantly (P </=.018) improved scores for QOL domains (activity limitations, symptoms, emotional function, and exposure to environmental stimuli) and overall QOL, with a significantly greater proportion of zafirlukast-treated patients demonstrating clinically meaningful improvements (>/=0.5-unit change from baseline; P </=.037). The safety profile of zafirlukast was clinically indistinguishable from that of placebo. CONCLUSIONS: Zafirlukast is effective and well tolerated and improves QOL in the long-term treatment of patients with moderate reversible airflow obstruction.

Adolescent↗

PubMed1998

The snRNP-free U1A (SF-A) complex(es): identification of the largest subunit as PSF, the polypyrimidine-tract binding protein-associated splicing factor.

We have previously shown that a specific monoclonal antibody prepared against the U1A protein, MAb 12E12, is unique in its ability to recognize a form of U1A which is not associated with the U1snRNP. This unique form of U1A, termed snRNP-free U1A or SF-A, was found to be complexed with a novel set of non-snRNP proteins (O'Connor et al., 1997, RNA 3:1444-1455). Here we demonstrate that the largest protein in these SF-A complex(es), p105, is the polypyrimidine-tract binding protein-associated factor (PSF), an auxiliary splicing factor. We show that PSF copurifies and co-immunoprecipitates with SF-A from 293T cell nucleoplasm and that it interacts with SF-A in vitro. In addition, we show that MAb 12E12 inhibits both splicing and polyadenylation in an in vitro coupled splicing and polyadenylation reaction. This suggests that SF-A and/or the SF-A complex(es) perform an important function in both processing reactions and possibly in last exon definition.

Amino Acid Sequence↗

PubMed1998

Animal models of heterotopic ossification.

Heterotopic ossification is often a severe clinical complication of joint arthroplasty, neurologic trauma, and muscle injury. In rare genetic disorders, such as fibrodysplasia ossificans progressiva, heterotopic ossification can be crippling and often leads to premature death. Reliable animal models of heterotopic ossifications that mimic pathologies seen in man would be invaluable for the development of new treatments to combat heterotopic ossification. Various methods used to induce heterotopic ossification in animals including the use of bone morphogenetic proteins, urinary tract epithelia, and transformed cell lines are described. Genetic animal models of heterotopic ossification and various miscellaneous examples of heterotopic ossification in animals are described. Finally, the use of transgenic mice to manipulate bone morphogenetic protein expression is discussed as a possible future animal model of heterotopic ossification.

Animals↗

PubMed1997

Beneficial effect of both tranexamic acid and aprotinin on blood loss reduction in reoperative valve replacement surgery.

BACKGROUND: Blood loss after cardiac surgery is a continuing concern of caregivers and patients. The acute inflammatory reaction initiated by the extracorporeal circuitry, necessary to perform the procedure, stimulates the coagulation cascade, and the resultant hyperfibrinolysis is considered to be a major contributing factor of blood loss. The necessity to reduce transfused blood products after cardiac surgery is important, as it reduces the potential transmission of serious viral infections, improves operative outcomes, and provides containment of costs. The purpose of this study was to compare the effect of synthetic antifibrinolytic tranexamic acid with naturally occurring antifibrinolytic aprotinin on blood loss and to study requirements for transfusion of blood products after repeat cardiac valve surgery. METHODS AND RESULTS: Two randomized trials had been previously conducted, each comparing the respective treatment groups, aprotonin (AP group) and transexamic acid (TA group), with a control group [placebo (P)] in double-blind fashion with the same inclusion and exclusion criteria. The number of patients in the four designated groups are as follows: TA, 22; TA-P, 19; AP, 24; and AP-P, 36. The dosage of aprotinin (high-dose) encompassed a 280-mg loading dose infused after induction of anesthesia, 280 mg in the CPB prime solution, and 70 mg/h for a period of 6 hours. The tranexamic acid dose was 10 mg infused in 500 mL of normal saline. The blood loss was measured intraoperatively and postoperatively. The transfusion of homologous blood products was conducted in a standardized fashion. Both the TA and AP groups lost less blood intraoperatively, in total, less than either of the placebo groups, and less blood postoperatively than the TA-P group (P<.05). The postoperative blood loss (median) was 538 mL for the TA group, 455 mL for the AP group, and for the respective placebo groups, 1170 mL and 595 mL. The total blood loss was 1340 mL for the TA group, 1383 mL for the AP group, and 3250 mL and 2450 mL, respectively for the placebo groups. The total blood product use revealed no differences between the two placebo groups (P=NS) nor between the two treatment groups (P=NS). CONCLUSIONS: Tranexamic acid and aprotinin are both effective in reducing intraoperative and postoperative blood loss and the need for blood product transfusion for patients undergoing reoperative cardiac valvular surgery.

Adult↗

PubMed1997

Tranexamic acid reduces blood loss and transfusion in reoperative cardiac surgery.

PURPOSE: The objective of this study was to assess the effect of tranexamic acid (TA), a synthetic antifibrinolytic, on blood loss and the need for transfusion of blood products following repeat cardiac valve surgery. METHODS: After ethics committee approval, 41 patients scheduled for reoperative valve replacement were enrolled in this randomized, double blind, placebo controlled study. Patients were randomized to receive TA (10 g in 500 ml NSaline) or placebo (NSaline) as an iv bolus over 30 min, after anaesthesia induction and prior to skin incision. Intraoperative blood loss was assessed by estimating blood volume on drapes, weighing surgical sponges, and measuring suction bottle returns. Postoperative blood loss was measured from mediastinal chest tube drainage following surgery. Blood products were transfused according to a standardized protocol. RESULTS: Patient demographics were similar for age, sex, cardiopulmonary bypass pump time, cross clamp time, surgical time, preoperative haemoglobin, coagulation profile, and the number of valves replaced during surgery. Tranexamic acid administration reduced intraoperative blood loss [median (range)] from 1656 (575-6270) to 720 ml (355-5616) (P < 0.01) and postoperative blood loss from 1170 (180-4025) to 538 ml (135-1465) (Intent to Treat n = 41, P < 0.01). The total red blood cells transfused (median, range) was reduced from 1500 (0-9300) ml to 480 (0-2850) ml (P < 0.01) in the TA group. In hospital complications and mortality rates were not reduced in the TA group. CONCLUSION: Tranexamic acid reduced blood loss and the need for blood product transfusion and appears to be an effective treatment for patients undergoing reoperative cardiac valvular surgery.

Antifibrinolytic Agents↗

PubMed1997

Amrinone versus dobutamine in cardiac surgical patients with severe pulmonary hypertension after cardiopulmonary bypass: a prospective, randomized double-blinded trial.

We compared the relative effects of dobutamine (5 micrograms/kg/min) and amrinone (1.0 mg/kg bolus followed by 10 micrograms/kg/min) on right and left ventricular function and pulmonary arterial pressures during weaning from cardiopulmonary bypass in patients with a mean preoperative pulmonary pressure > 30 mmHg. Twenty patients scheduled for mitral valve replacement were studied in a prospective, randomized, double-blind trial. Patients receiving amrinone had a greater increase in cardiac index (CI) of 1.38 (+/-0.95) litre/min/m2 at separation vs 0.69 (+/-0.63) litre/min/m2 in the dobutamine group (P < 0.05). The amrinone group also had a greater increase in right ventricular ejection fraction (0.15 +/- 0.08 at separation from cardiopulmonary bypass versus an increase of 0.04 +/- 0.11 in those receiving dobutamine; P < 0.005). Amrinone produced a larger decrease in pulmonary artery wedge pressure 8.0 (+/-4.4) mmHg vs 0.75 (+/-6.6) mmHg at separation; pulmonary artery systolic and diastolic pressures also were reduced more in the amrinone group. There were no differences in heart rate, mean arterial pressure, central venous pressure and right ventricular stroke work index between patient groups. In the doses chosen, the use of amrinone compared to dobutamine was associated with a reduction in pulmonary arterial pressures and an increase in cardiac index and right ventricular ejection fraction after separation from bypass in patients with severe preoperative pulmonary hypertension.

Amrinone↗

PubMed1997

YRA1, an essential Saccharomyces cerevisiae gene, encodes a novel nuclear protein with RNA annealing activity.

The complexity of eukaryotic mRNA processing suggests a need for certain factors, called RNA chaperones, that can modulate RNA secondary structure as well as the interactions between pre-mRNA and trans-acting components. To identify factors that may fulfill this role in the yeast Saccharomyces cerevisiae, we fractionated whole-cell extracts and assayed for activity that could facilitate a specific RNA-RNA annealing reaction. We detected one strong RNA annealing activity and purified it to homogeneity. This previously undescribed factor, Yra1p, is localized to the nucleus; its sequence contains one RNP-motif RNA-binding domain. The YRA1 gene contains a 766-nt intron, the second-largest identified in this organism, and Yra1p serves an essential, nonredundant function. Taken together, our findings indicate that Yra1p is likely to have an important role in S. cerevisiae nuclear pre-mRNA metabolism.

Amino Acid Sequence↗

PubMed1997

Identification of a novel, non-snRNP protein complex containing U1A protein.

Mouse monoclonal antibodies (MAbs) were generated against Escherichia coli-produced U1snRNP-A (U1A) protein. U1A-specific MAbs as well as MAbs that reacted with both U1A and U2snRNP-B" (U2B") were isolated. MAb 12E12 was unique among the characterized MAbs because it failed to immunoprecipitate U1A protein produced by in vitro transcription and translation using rabbit reticulocyte lysates. However, when U1A protein was made using a wheat germ extract, MAb 12E12 could immunoprecipitate U1A quite readily, as did the other MAbs. These data suggest that the MAb 12E12 epitope is masked when U1A is prepared in reticulocyte lysate. Further studies showed that MAb 12E12 recognizes an epitope that is masked when U1A protein is bound to U1 RNA. The unique nature of MAb 12E12 was used to demonstrate that U1A could be immunoprecipitated from whole-cell extracts in a form that was free of U1 RNA and other snRNP components. However, this snRNP-free U1A (SF-A) was found to co-immunoprecipitate with a unique set of non-snRNP proteins. In order to confirm that U1A exists in at least two distinct complexes (snRNP bound and snRNP free), [35S]-labeled nucleoplasmic extracts were analyzed by sucrose density gradient fractionation and immunoprecipitation. MAb 12E12 specifically immunoprecipitated SF-A, which migrated in a novel non-snRNP complex. Specifically, proteins of approximately 58, 59, 63, 65, and 105 kDa co-sedimented and co-immunoprecipitated with SF-A. Our data show that a significant portion of the cellular U1A (at least 3% or approximately 30,000 molecules) exists in the nucleoplasm in one or more novel complexes. Our previous studies have demonstrated an effect of purified U1A on polyadenylation of pre-mRNAs and, consistent with this finding, purified antibodies to SF-A significantly diminish polyadenylation in vitro.

Animals↗

PubMed1996

Nucleus-associated pools of Rna1p, the Saccharomyces cerevisiae Ran/TC4 GTPse activating protein involved in nucleus/cytosol transit.

Rna1p is the GTPase activating enzyme for Ran/TC4, a Ras-like GTPase necessary for nuclear/cytosolic exchange. Although most wild-type Rna1p is located in the cytosol, we found that the vast majority of the mutant Rna1-1p and, under appropriate physiological conditions, a small portion of the wild-type Rna1p cofractionate with yeast nuclei. Subnuclear fractionation studies show that most of the Rna1p is tightly associated with nuclear components, and that a portion of the active protein can be solubilized by treatments that fail to solubilize inactive Rna1-1p. To learn the precise nuclear locations of the Rna1 proteins, we studied their subcellular distributions in HeLa cells. By indirect immuno-fluorescence we show that wild-type Rna1p has three subcellular locations. The majority of the protein is distributed throughout the cytosol, but a portion of the protein is nucleus-associated, located at both the cytosolic surface and within the nucleoplasm. Mutant Rna1-1p is found at the outer nuclear surface and in the cytosol. We propose that a small pool of the wild-type Rna1p is located in the nuclear interior, supporting the model that the same components of the Ran/TC4 GTPase cycle exist on both sides of the nuclear membrane.

Base Sequence↗

PubMed1996

Interaction between the U1 snRNP-A protein and the 160-kD subunit of cleavage-polyadenylation specificity factor increases polyadenylation efficiency in vitro.

We have previously shown that the U1 snRNP-A protein (U1A) interacts with elements in SV40 late polyadenylation signal and that this association increases polyadenylation efficiency. It was postulated that this interaction occurs to facilitate protein-protein association between components of the U1 snRNP and proteins of the polyadenylation complex. We have now used GST fusion protein experiments, coimmunoprecipitations and Far Western blot analyses to demonstrate direct binding between U1A and the 160-kD subunit of cleavage-polyadenylation specificity factor (CPSF). In addition, Western blot analyses of fractions from various stages of CPSF purification indicated that U1A copurified with CPSF to a point but could be separated in the highly purified fractions. These data suggest that U1A protein is not an integral component of CPSF but may be able to interact and affect its activity. In this regard, the addition of purified, recombinant U1A to polyadenylation reactions containing CPSF, poly(A) polymerase, and a precleaved RNA substrate resulted in concentration-dependent increases in both the level of polyadenylation and poly(A) tail length. In agreement with the increase in polyadenylation efficiency caused by U1A, recombinant U1A stabilized the interaction of CPSF with the AAUAAA-containing substrate RNA in electrophoretic mobility shift experiments. These findings suggest that, in addition to its function in splicing, U1A plays a more global role in RNA processing through effects on polyadenylation.

Glutathione Transferase↗

PubMed1996

On line ST-segment analysis for detection of myocardial ischaemia during and after coronary revascularization.

PURPOSE: A paucity of information exists to validate the accuracy and reliability of ECG monitoring in the operating room or ICU. The purpose of this study was to determine the accuracy, sensitivity, specificity, and predictive values of the Marquette ECG monitor for detection of perioperative myocardial ischaemia (PMI) as measured by ST segment changes in a high risk population. METHODS: Monitoring for PMI in 28 patients scheduled for aortocoronary bypass surgery was done with the Cardiodata PR ambulatory continuous electrocardiography (ACECG) monitor lead V5, and compared with lead V5 of the Marquette Series 7000 ECG/Surgical operating room monitor, and ECG/Resp ICU monitor. The Marquette lead V5 was evaluated using current criteria for the assessment of diagnostic tests including concordance, sensitivity, specificity, positive and negative predictive values, false positive and false negative rates and compared with the ACECG monitor which served as the reference or "gold standard." Agreement beyond chance between the two methods was assessed using the Kappa statistic. RESULTS: Of the 53 observation data points, 27 were defined as ischaemic episodes by ACECG. Concordance between lead V5 in each system was 83% (44/53 episodes). Discordance was 17% (9/53 episodes), predominantly in the postbypass interval (77%, 7/9; P = 0.0184). The incidences of false negatives and false positives for Marquette lead V5 was 26% (7/27) and 7.7% (2/26), respectively. The sensitivity and specificity of the Marquette was 0.74 and 0.92. Positive predictive value was 0.91, negative predictive value was 0.77, and Kappa statistic was 66%. CONCLUSION: Automated ST segment analysis with the Marquette Series 7000 monitoring system demonstrates good diagnostic accuracy, moderate sensitivity, and high specificity. However, clinically significant false negative and false positive rates of ischaemia detection are associated with its use, especially in the postoperative period.

Electrocardiography↗

PubMed1995

The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2.

Fragile X Mental Retardation Syndrome is the most common form of hereditary mental retardation, and is caused by defects in the FMR1 gene. FMR1 is an RNA-binding protein and the syndrome results from lack of expression of FMR1 or expression of a mutant protein that is impaired in RNA binding. The specific function of FMR1 is not known. As a step towards understanding the function of FMR1 we searched for proteins that interact with it in vivo. We have cloned and sequenced a protein that interacts tightly with FMR1 in vivo and in vitro. This novel protein, FXR2, is very similar to FMR1 (60% identity). FXR2 encodes a 74 kDa protein which, like FMR1, contains two KH domains, has the capacity to bind RNA and is localized to the cytoplasm. The FXR2 gene is located on human chromosome 17 at 17p13.1. In addition, FMR1 and FXR2 interact tightly with the recently described autosomal homolog FXR1. Each of these three proteins is capable of forming heteromers with the others, and each can also form homomers. FXR1 and FXR2 are thus likely to play important roles in the function of FMR1 and in the pathogenesis of the Fragile X Mental Retardation Syndrome.

Amino Acid Sequence↗

PubMed1995

Topographic changes in a heterochromatic chromosome block in humans (15P) during formation of the nucleolus.

Fluorescence in situ hybridization and multispectral confocal laser scanning microscopy revealed a highly dynamic nucleolar-associated chromosome 15 satellite III heterochromatin cluster in humans. This nucleolar-associated DNA was highly decondensed at the metaphase plate compared with its topography at interphase and appeared to act as a centre for the post-mitotic reorganization of the nucleolus. Our data showed unexpected trans-mitotic changes in the topography of this nucleolar-associated satellite III DNA that suggest that this locus-specific heterochromatin superstructure may be involved in nucleolar organization.

Cell Nucleolus↗