Nomenclature for ion channel subunits.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
R Reed
Publications and source records attributed to R Reed.
Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly.
Recent studies indicate that splicing of pre-messenger RNA and export of mRNA are normally coupled in vivo. During splicing, the conserved mRNA export factor Aly is recruited to the spliced mRNA-protein complex (mRNP), which targets the mRNA for export. At present, it is not known how Aly is recruited to the spliced mRNP. Here we show that the conserved DEAD-box helicase UAP56, which functions during spliceosome assembly, interacts directly and highly specifically with Aly. Moreover, UAP56 is present together with Aly in the spliced mRNP. Significantly, excess UAP56 is a potent dominant negative inhibitor of mRNA export. Excess UAP56 also inhibits the recruitment of Aly to the spliced mRNP. Furthermore, a mutation in Aly that blocks its interaction with UAP56 prevents recruitment of Aly to the spliced mRNP. These data suggest that the splicing factor UAP56 functions in coupling the splicing and export machineries by recruiting Aly to the spliced mRNP.
Adenosine Triphosphatases↗
Statement of intent--MFDS/MFD new regulations 2001.
Explore the source record for details and available documents.
Credentialing↗
Pregnancy following uterine fibroid embolization.
OBJECTIVE: This paper seeks to evaluate the ability to deliver term pregnancies following uterine fibroid embolization, and to identify impediments to pregnancy in the embolization procedure. STUDY DESIGN: Four physicians performed embolization procedures at various facilities. Patients were asked if fertility was an issue prior to embolization. We measured follicle-stimulating hormone levels before and after embolization. Clinical follow-up, six months following embolization was obtained by interview. Patients were questioned regarding attempts to conceive, menstrual history, and subsequent pregnancy. MAIN OUTCOME MEASURES: Complications were calculated upon the entire patient population, whether or not fertility was identified as a goal. Fertility risks from embolization were identified. We measured radiation exposure in a random consecutive group of 50 women undergoing embolization. All patients who conceived were asked the details of the pregnancy. RESULTS: Four hundred women underwent uterine fibroid embolization between 1996 and 1999. One hundred and thirty nine patients stated a desire for fertility after embolization. Of these, 52 were <40 years old. Seventeen pregnancies have been reported in 14 women. Five spontaneous abortions were observed. Ten women have had normal term deliveries and two women are currently pregnant. No perfusion problems, either during the pregnancy or labor, were reported. The average radiation dosage calculated for 50 women undergoing embolization was 14 rads. Four women under 45 years old suffered premature menopause (10/1000). Two women underwent hysterectomy as a complication of embolization (5/1000). CONCLUSION: The risks of infertility following embolization, premature menopause, and hysterectomy are small, as is the radiation exposure during embolization. These risks compare favorably with those associated with myomectomy. Fertility rates appear similar to patients undergoing myomectomy. No problems, either during pregnancy or delivery, have been observed after embolization. The course of pregnancy and delivery was normal after embolization with no maternal or fetal complications reported. These findings confirm results from other centers. Desire for future pregnancy is not a contraindication to fibroid embolization.
Abortion, Spontaneous↗
A Ran-independent pathway for export of spliced mRNA.
All major nuclear export pathways so far examined follow a general paradigm. Specifically, a complex is formed in the nucleus, containing the export cargo, a member of the importin-beta family of transporters and RanGTP. This complex is translocated across the nuclear pore to the cytoplasm, where hydrolysis of the GTP on Ran is stimulated by the GTPase-activating protein RanGAP. The activity of RanGAP is increased by RanBP1, which also promotes disassembly of RanGTP-cargo-transporter complexes. Here we investigate the role of RanGTP in the export of mRNAs generated by splicing. We show that nuclear injection of a Ran mutant (RanT24N) or the normally cytoplasmic RanGAP potently inhibits the export of both tRNA and U1 snRNA, but not of spliced mRNAs. Moreover, nuclear injection of RanGAP together with RanBP1 blocks tRNA export but does not affect mRNA export. These and other data indicate that export of spliced mRNA is the first major cellular transport pathway that is independent of the export co-factor Ran.
Active Transport, Cell Nucleus↗
A new view of mRNA export: separating the wheat from the chaff.
Current models for the export of messenger RNA share the notion that the highly abundant class of nuclear RNA-binding proteins--the hnRNP proteins--have a key role in exporting RNA. But recent studies have led to a new understanding of several non-hnRNP proteins, including SR proteins and the conserved mRNA export factor ALY, which are recruited to the mRNA during pre-mRNA splicing. These studies, together with older work on hnRNP particles and assembly of the spliceosome, lead us to a new view of mRNA export. In our model, the non-hnRNP factors form a splicing-dependent mRNP complex that specifically targets mature mRNA for export, while hnRNP proteins retain introns in the nucleus. A machinery that is conserved between yeast and higher eukaryotes functions to export the mRNA.
Animals↗
In situ and small invasive breast cancer register in Victoria, 1988 to 1992: tumour characteristics and patient management.
BACKGROUND: All cases of in situ and invasive breast cancer are reported to the Victorian Cancer Registry. In 1988 a special subregister of all cases of carcinoma in situ and small invasive cancers up to 10 mm in size was established--the In situ and Small Invasive Breast Cancer Register (ISSIBCR). This was unique in being a population-based register and only possible because in Victoria, as in some other Australian states, all cancers including in situ disease are reported to the Central Cancer Registry. METHODS: Between 1 January 1988 and 31 December 1992, 517 cases of in situ cancers and 892 invasive cancers of < or =10 mm in diameter were registered. During the study period, mammography screening was progressively introduced in Victoria and the number of cases, in both categories registered annually, doubled. RESULTS: The method of detection, the pathology and treatment of these lesions are described. It is of interest that 46.5% of the in situ cancers and 68.8% of the invasive cancers were detected either by the patient or her doctor on clinical examination. Total mastectomy was the method of treatment in 35.4% of in situ cancers and 42.0% of small invasive tumours. Only 38.0% of patients with small invasive cancers treated by breast-conserving surgery had irradiation of the affected breast. CONCLUSIONS: This register provides a valuable resource for the follow up of the natural history and outcome of treatment of the affected women.
Adult↗
Erythema gyratum repens.
BACKGROUND: Erythema gyratum repens is a rare, clinically specific, and distinctive paraneoplastic syndrome. It is associated with internal malignancy in 82% of patients. OBJECTIVE: A 58-year-old man with erythema gyratum repens is described. On diagnosis of his eruption, a malignancy work-up revealed a 9-mm pulmonary adenocarcinoma. Removal of the carcinoma resulted in clearing of the erythema. RESULTS: Erythema gyratum repens is most commonly associated with bronchial, esophageal, and breast cancer. It has also rarely been reported in patients without evidence of malignancy. The histopathologic findings are nonspecific. Direct immunofluorescence has sometimes revealed C3, C4, or immunoglobulin G at the basement membrane zone. CONCLUSION: The etiology of erythema gyratum repens is unknown, although an immune response is postulated. Treatment involves treating the underlying malignancy.
Erythema↗
An upstream AG determines whether a downstream AG is selected during catalytic step II of splicing.
Specific mechanisms must exist to ensure fidelity in selecting the AG dinucleotide that functions as the 3' splice site during the second transesterification step of splicing. Here we show that the optimal location for this AG is within a narrow distance (19 to 23 nucleotides [nt]) downstream from the branch point sequence (BPS). Contrary to previous expectations, AGs located less than 23 nt from the BPS are always recognized, even when a second AG located more optimally downstream is used in the transesterification reaction. Indeed, the AG closest to the BPS actually dictates the precise location of the AG that engages in the reaction. This mechanism, in which the AG is identified by a general localization step followed by a precise localization step, may be used to achieve fidelity while allowing flexibility in the location of 3' splice sites.
Cell Nucleus↗
EKG analysis skills of family practice residents in the United Arab Emirates: a comparison with US data.
BACKGROUND AND OBJECTIVES: Concern has been raised about the electrocardiogram (EKG) analysis skills of family practice residents in the United States. This study examined EKG analysis skills of family practice residents, medical students, interns, and general practitioners (GPs) in the United Arab Emirates (UAE), a different environment. METHODS: The measurement instrument was a set of 10 EKGs, used in a study of US family practice residents. Two of the EKGs were normal, and there were 14 clinical abnormalities in the remainder. RESULTS: There was no significant difference in the correct diagnosis of acute myocardial infarction between US family practice residents and UAE family practice residents, medical students, or GPs. Interns' diagnoses were significantly poorer. The mean score for correctly identifying acute myocardial infarction and both normal EKGs was not significantly different between groups: 2.50 medical students, 2.35 interns, 2.58 UAE family practice residents, 2.67 FD, and 2.55 US family practice residents. However, the US family practice resident mean score of 11.26 for all 16 clinical findings was significantly higher than any group in the UAE: 5.35 medical students, 5.87 interns, 6.08 UAE family practice residents, 5.69 family physicians. CONCLUSIONS: Difficulty in EKG interpretation transcends geographic boundaries, suggesting that new approaches to teaching these skills need to be explored. Improved EKG reading skills by family physicians are generally needed in both the United States and the UAE.
Clinical Competence↗
Fathers: those engrossing first minutes.
Explore the source record for details and available documents.
Father-Child Relations↗
Insights from a large rural population laboratory. Health census '89 and '99.
PURPOSE: Data are limited on health status behaviors and use of health services for rural residents. Yet rural areas now have higher rates of chronic diseases, such as coronary heart disease, than urban areas.METHODS: A population laboratory (Health Census) was established in rural Central NY (Otsego County) to study these variables in this population. HC '89 was a door-to-door enumeration of all permanent households in the country. In 1989, 44,500 adults in 18,000 households provided data on individual health screenings, cancer and cardiovascular risk factors, health behaviors, chronic disease, access to care, preventive services use, health insurance and emergency department utilization. Data collection for HC '99 will identify 10-year trends; it also includes baseline data for children. Also, households in six surrounding rural counties (N = 10,000) were sampled; cost benefits of different survey methods were assessed. Questions about perceived health status, and special health and pediatric preventive care needs were included. After 10 years of social change, many limitations of traditional survey methods became apparent; much more varied and frequent types of follow-up were needed to achieve adequate response rates.RESULTS: The HC '89 final response rate was 86%. There were significant socioeconomic gradients in use of preventive services (blood pressure screening, rectal exams, mammograms and Pap smears). Adults without health insurance or Medicaid had much lower utilization rates of screening tests and higher rates of cigarette smoking and obesity. Several community intervention programs were implemented as a result of HC '89. HC '99 provides additional analyses to examine change in preventive service use, self-reported chronic disease, and health services use; it will likely verify the persistence of socioeconomic gradients. Response rates are similar to '89, but achieved only with more intensive reinforcement.CONCLUSIONS: HC '89 confirmed a lag in positive health indices in rural populations in Central NY. Both newer methodologies now needed and results of HC '99 will serve as guides for smaller rural counties to develop affordable local health surveys and plan intervention strategies.
Journal Article↗
The protein Aly links pre-messenger-RNA splicing to nuclear export in metazoans.
In metazoans, most pre-messenger RNAs contain introns that are removed by splicing. The spliced mRNAs are then exported to the cytoplasm. Recent studies showed that splicing promotes efficient mRNA export, but the mechanism for coupling these two processes is not known. Here we show that Aly, the metazoan homologue of the yeast mRNA export factor Yralp (ref. 2), is recruited to messenger ribonucleoprotein (mRNP) complexes generated by splicing. In contrast, Aly does not associate with mRNPs assembled on identical mRNAs that already have no introns or with heterogenous nuclear RNP (hnRNP) complexes. Aly is recruited during spliceosome assembly, and then becomes tightly associated with the spliced mRNP. Aly shuttles between the nucleus and cytoplasm, and excess recombinant Aly increases both the rate and efficiency of mRNA export in vivo. Consistent with its splicing-dependent recruitment, Aly co-localizes with splicing factors in the nucleus. We conclude that splicing is required for efficient mRNA export as a result of coupling between the splicing and the mRNA export machineries.
Animals↗
Eletriptan in acute migraine: a double-blind, placebo-controlled comparison to sumatriptan.
Explore the source record for details and available documents.
Acute Disease↗
Mechanisms of fidelity in pre-mRNA splicing.
The pre-mRNA splicing machinery consists of five small nuclear RNAs (U1, U2, U4, U5 and U6) and more than fifty proteins. Over the past year, important advances have been made in understanding how these factors function to achieve fidelity in splicing. Of particular note were the discoveries that the splicing factor U2AF(35) recognizes the AG dinucleotide at the 3' splice site early in spliceosome assembly, that a DEAD-box ATPase, Prp28, triggers specific rearrangements of the spliceosome, and that the splicing factor hSlu7 functions in the fidelity of AG choice during catalytic step II of splicing.
Animals↗
Functional association of U2 snRNP with the ATP-independent spliceosomal complex E.
In the current model for spliceosome assembly, U1 snRNP binds to the 5' splice site in the E complex followed by ATP-dependent binding of U2 snRNP to the branchpoint sequence (BPS) in the A complex. Here we report the characterization of highly purified, functional E complex. We provide evidence that this complex contains functional U2 snRNP and that this snRNP is required for E complex assembly. The BPS is not required for U2 snRNP binding in the E complex. These data suggest a model for spliceosome assembly in which U1 and U2 snRNPs first associate with the spliceosome in the E complex and then an ATP-dependent step results in highly stable U2 snRNP binding to the BPS in the A complex.
Adenosine Triphosphatases↗
Lowering dietary saturated fat and total fat reduces the oxidative susceptibility of LDL in healthy men and women.
The present study examined the effects of reducing dietary total fat and saturated fat (SFA) on LDL oxidative susceptibility in 27 healthy men and women (age 24-65 y). Each subject consumed each of three diets for 8 wk: an average American diet (AAD, 34% energy from fat, 15% from SFA), a Step-1 diet (29% fat, 9% SFA) and a very low SFA diet (Low-Sat, 25% fat, 6% SFA). In vitro LDL oxidation was assessed by copper-mediated oxidation, as measured by the kinetics of conjugated diene formation and lipid peroxide formation. Compared with the AAD, plasma LDL-cholesterol (LDL-C) and HDL cholesterol levels were 8% lower (P: = 0.16 and P: = 0.11, respectively), in subjects when they consumed the Step-1 diet and 11% (P: < 0.03) and 14% (P: < 0.057) lower, respectively, when they consumed the Low-Sat diet. Conjugated diene production and oxidation rate were 7% (P: < 0. 05) and 9% (P: < 0.05) lower, respectively. The reduction of lipid peroxide formation was 9% (P: < 0.05) in subjects when they consumed the Low-Sat diet vs. the AAD. In addition, lipid peroxide and conjugated diene formation were positively correlated with plasma total and LDL-C and apolipoprotein B (apo B) levels (r = 0.5-0.6, P: < 0.001), suggesting that quantity of LDL is an important determinant of oxidative modification. Furthermore, at the same level of apo B or LDL-C, LDL from subjects when they consumed either Step-1 or Low-Sat diets was less susceptible (P: < 0.05) to oxidation than those when they consumed the AAD, suggesting that qualitative changes also affect LDL oxidative susceptibility. Therefore, the benefits of lowering dietary SFA may extend beyond decreasing LDL-C levels and include favorable qualitative changes in LDL that further decrease risk of coronary heart disease.
Adult↗
Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures.
PURPOSE: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. METHODS: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. RESULTS: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. CONCLUSIONS: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.
Electric Stimulation Therapy↗