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Biomedical subjects

J Kantor

Publications and source records attributed to J Kantor.

At least 19 recordsLinked to original sources
PubMed2001

Detection of blood-borne cells in colorectal cancer patients by nested reverse transcription-polymerase chain reaction for carcinoembryonic antigen messenger RNA: longitudinal analyses and demonstration of its potential importance as an adjunct to multiple serum markers.

The use of reverse transcription-PCR (RT-PCR) to analyze cells in the blood of cancer patients for the detection of mRNA expressed in tumor cells has implications for both the prognosis and the monitoring of cancer patients for the efficacy of established or experimental therapies. Carcinoembryonic antigen (CEA) is expressed on approximately 95% of colorectal, gastric, and pancreatic tumors, and on the majority of breast, non-small cell lung, and head and neck carcinomas. CEA shed in serum is useful as a marker in only approximately 50% of colorectal cancer patients and rarely is shed by some other carcinoma types. RT-PCR has been used previously to detect CEA mRNA in cells in the blood and lymph nodes of cancer patients. Under the assay conditions validated in the studies reported here, 34 of 51 (67%) patients with different stages of colorectal cancer had blood cells that were positive by RT-PCR for CEA mRNA, whereas none of 18 patients with colonic polyps were positive; 2 of 60 apparently healthy individuals (who were age and sex matched with the carcinoma patients and were part of a colon cancer screening program as controls) were marginally positive. The results of CEA PCR in the blood of the carcinoma patients and the other groups showed strong statistical correlation with the disease (P2 < 0.0001). Analyses were carried out to detect both serum CEA protein levels and CEA mRNA in blood cells of colorectal carcinoma patients by RT-PCR. For all stages of disease, 18 of 51 patients (35%) were positive for serum CEA, whereas 35 of 51 (69%) were positive by RT-PCR. More importantly, only 5 of 23 (20%) of stage B and C colorectal cancer patients were positive for serum CEA, whereas 16 of 23 (70%) were positive by RT-PCR. The use of two other serum markers (CA19.9 and CA72-4) for colorectal cancer in combination with serum CEA scored two additional patients as positive; both were positive by RT-PCR for CEA mRNA. Pilot long-term longitudinal studies conducted before and after surgery identified some patients with CEA mRNA in blood cells that were negative for all serum markers, who eventually developed clinical metastatic disease. The studies reported here are the first to correlate RT-PCR results for CEA mRNA in blood cells with one or more serum markers for patients with different stages of colorectal cancer, and are the first long-term longitudinal studies to use RT-PCR to detect CEA mRNA in blood cells of cancer patients. Larger cohorts will be required in future studies to define the impact, if any, of this technology on prognosis and/or disease monitoring.

Adenocarcinoma↗
PubMed2001

Acquisition of CD80 (B7-1) by T cells.

Activation of T cells usually requires two signals. Signal 1 is mediated via a peptide-MHC on the APC; signal 2 is mediated via a costimulatory molecule on the APC surface. We demonstrate here that naive CD4(+) T cells actually acquire the costimulatory molecule CD80 (B7-1) from syngeneic APCs after activation. This phenomenon was demonstrated showing acquisition of CD80 by T cells from CD80/CD86 (B7-2) knockout mice, and by treating T cells with cyclohexamide to further rule out endogenous expression of CD80 by T cells. Moreover, no CD80 mRNA could be detected in T cells that had acquired CD80. The amount of acquisition of CD80 by T cells was shown to be directly related to both the strength of signal 1 and the amount of CD80 on the APC. Specificity of this acquisition was also shown by the lack of acquisition by T cells from CD28 knockout mice (implicating CD28 in this process), the lack of acquisition of CD40 (another molecule on the APC surface) by T cells, and confocal microscopy studies. We demonstrate for the first time that 1) naive T cells, following acquisition of CD80 from APCs, were themselves shown to be capable of acting as APCs; and 2) memory T cells that have acquired CD80 from APCs undergo apoptosis in the presence of increased levels of signal 1. Thus we demonstrate both immunostimulatory and immunoregulatory functions as a result of CD80 acquisition by different T cell populations.

Animals↗
PubMed2001

Treatment options for diabetic neuropathic foot ulcers: a cost-effectiveness analysis.

BACKGROUND: Diabetic foot ulcers are a common problem and result in more than 85,000 lower extremity amputations each year in the United States. Studies have suggested that between 25% and 50% of costs related to inpatient diabetes care may be directly attributable to the diabetic foot. Novel treatments for these wounds, while expensive, have been reported to improve healing rates, although no formal cost effectiveness analyses have been performed in order to address the cost effectiveness of a given therapy. OBJECTIVE: To estimate the cost effectiveness of common treatment strategies for diabetic neuropathic foot ulcers. METHODS: Four main options are available for the treatment of diabetic foot ulcers: (1) standard care (SC), (2) standard treatment in a specialized wound care center (WCC), (3) treatment with becaplermin, (4) or treatment with platelet releasate (PR). We utilized effectiveness data from published clinical trials, meta-analyses, and a database that includes data on 26,599 patients with these wounds. Effectiveness was assessed as a percentage of ulcers healed at 20 and 32 weeks. RESULTS: Baseline effectiveness (with 95% confidence intervals) for SC, becaplermin, PR, and WCC care were 30.9% (26.6, 35.1), 43.0% (37.3, 48.7), 36.8% (35.4, 38.2), and 35.6% (34.8, 36.4), respectively. Cost:effectiveness ratios for PR versus SC and becaplermin versus SC were 414.40 and 36.59, respectively. Therefore the incremental cost of increasing the odds of healing by 1% over standard therapy was $414.40 for PR and $36.59 for becaplermin. CONCLUSIONS: PR, becaplermin, and WCC care all provided improved healing rates over standard care, and becaplermin was less expensive and more effective than PR after 20 weeks of care.

Ambulatory Care Facilities↗
PubMed2001

Antiplatelet agents for secondary prevention of ischemic stroke.

OBJECTIVE: To review and summarize the efficacy, mechanisms of action, and cost of the options available when choosing antiplatelet agents for secondary stroke prevention. DATA SOURCES: This article is based on a review of the literature found with MEDLINE, CINAHL, and Cochrane Reviews (1980-June 2000) and abstracts from relevant international scientific meetings. We searched for the terms aspirin, ticlopidine, dipyridamole, antiplatelet, and clopidogrel. STUDY SELECTION: English-language articles, both reviews and original studies, were evaluated, and all information considered relevant was included in this review. In addition, guidelines from the American Heart Association are included. DATA SYNTHESIS: Aspirin is a relatively inexpensive and effective agent for secondary stroke prevention, and lower doses of aspirin appear as effective as higher doses. Ticlopidine has been used alone or in combination with aspirin, but serious adverse effects have limited its use. Clopidogrel has emerged as a safe and effective alternative to ticlopidine and lacks some of the serious adverse effects associated with ticlopicine, but is not superior to aspirin in secondary stroke prevention. Unlike previous studies, one recent trial showed that dipyridamole in combination with aspirin is superior to aspirin alone. CONCLUSIONS: Antiplatelet therapy is a key component of secondary prevention strategies in ischemic stroke. While aspirin has been the cornerstone in the management of stroke, other classes of antiplatelet drugs present new opportunities to optimize antiplatelet therapy.

Aspirin↗
PubMed2001

Effectiveness of platelet releasate for the treatment of diabetic neuropathic foot ulcers.

OBJECTIVE: The goal of this study was to specifically estimate the effectiveness of platelet releasate, a widely available treatment administered by a proprietary group of wound care centers (WCCs) for the treatment of diabetic neuropathic foot ulceration. RESEARCH DESIGN AND METHODS: Treatment effectiveness was estimated in a retrospective cohort study controlling for treatment selection bias using logistic regression-derived propensity scores. RESULTS: Platelet releasate was more effective than standard care. The relative risk for a wound to heal after treatment with platelet releasate compared with standard care at a WCC varied from 1.14 (95% CI 1.03-1.27) to 1.59 (1.49-1.70). The effect was greatest in those with the most severe wounds, i.e., large wounds that affect deeper anatomical structures. CONCLUSIONS: Within the limitations of the ability of propensity score analysis to control for selection bias, platelet releasate is more effective than standard therapy. This effect is more pronounced in more severe wounds. Unfortunately, severe wounds have not been evaluated in randomized clinical trials of new interventions. We encourage the inclusion of these patients in future trials.

Aged↗
PubMed2000

Risk factors for delayed healing of neuropathic diabetic foot ulcers: a pooled analysis.

OBJECTIVE: To estimate the effect of various risk factors on the probability that neuropathic diabetic foot ulcers will heal within 20 weeks of care. DESIGN AND SETTING: A pooled or meta-analysis of individual patient data from the standard care arms of 5 randomized clinical trials was conducted. We analyzed 586 subjects with diabetes mellitus who had a neuropathic diabetic foot ulcer. All patients received good wound care, debridement, and "off-loading" of the wound. MAIN OUTCOME MEASURE: Multivariable logistic regression was used to calculate the magnitude of the association of each risk factor with patients having healed wounds. RESULTS: Logistic regression odds ratios (ORs; 95% confidence intervals [95% CIs]) revealed that those patients with a diabetic neuropathic foot ulcer that healed within 20 weeks using standard care were more likely to have a smaller wound (OR = 0.67; 95% CI, 0.55-0.81), a wound that existed for a shorter period (OR = 0.73; 95% CI, 0.61-0.87), and be nonwhite (OR = 0.64; 95% CI, 0.43-0.96) compared with patients whose wounds did not heal within 20 weeks. The patient's age (OR = 0.99; 95% CI, 0.89-1.01), serum level of glycosylated hemoglobin at the start of the study (OR = 1.03; 95% CI, 0.97-1.10), and sex (OR = 1. 02; 95% CI, 0.69-1.50) were unassociated with the probability of wound healing. Substantial heterogeneity was not found among the studies. CONCLUSIONS: A standard care regimen for diabetic neuropathic foot ulcers is most likely to be effective for patients who have wounds that are small and of brief duration. This information should help dermatologists decide initially whether to use standard care, to try a new treatment, or to refer the patient to a specialty center.

Adult↗
PubMed2000

A multicentre study of percentage change in venous leg ulcer area as a prognostic index of healing at 24 weeks.

Venous leg ulcers, which may take months to heal, account for 40-70% of all lower extremity chronic wounds. New treatment options for venous leg ulcers have recently been proposed, and therefore deciding which patients are candidates for these novel-and often expensive-treatments is an important task. Moreover, researchers conducting clinical trials often wish to enroll patients who are unlikely to heal in order to minimize sample sizes needed and research costs. Our purpose was to assess the use of percentage change in venous leg ulcer area over the first few weeks of treatment as a prognostic indicator of healing or non-healing at 24 weeks. We conducted a cohort study based on an existing data set from a multicentre randomized clinical trial that enrolled 104 patients. Wounds were measured using digital planimetry for 4 consecutive weeks following the inception of good wound care. Utilizing the Wilcoxon rank sum (Mann-Whitney) test, we found that percentage change in area over time distinguished between those who healed and those who failed to heal after 24 weeks of good wound care (P < 0.05). The rate of healing, or area healed per week, did not differentiate between those who healed at 24 weeks and those who did not, as all patients had similar rates of healing over the first 4 weeks of treatment. Percentage change in area from baseline to week 4 provided the best combination of positive and negative predictive values (68.2%, 74.7%) and the largest area under the receiver operating characteristic curve (0.75). Thus, percentage change in area over the first 4 weeks of treatment represents a practical and predictive measure of complete wound healing by 24 weeks.

Cohort Studies↗
PubMed2000

Intraneural sciatic nerve pressures relative to the position of the hip and knee: a human cadaveric study.

OBJECTIVES: To determine the effects of ipsilateral hip and knee position on intraneural sciatic nerve pressures. DESIGN: Intraneural sciatic nerve pressures measured in intact, fresh cadaveric specimens relative to ipsilateral hip and knee positions. LOCATION: Medical school anatomy laboratory. SUBJECTS: Randomly acquired adult cadavers. INTERVENTION: Pressure transducer placed within the sciatic nerve distal to the femoral attachment of the gluteus maximus. Intraneural pressures measured with the hip placed in 0, 45, and 90 degrees of flexion while the knee was positioned in 90, 45, and 0 degrees of flexion. MAIN OUTCOME MEASUREMENTS: Tissue fluid pressures within the sciatic nerve relative to the position of the ipsilateral hip and knee. Tissue fluid pressure within the sciatic nerve exceeded previously defined critical thresholds for alteration of neural microcirculation and function. Although increased intraneural pressures were realized as the hip was positioned in greater flexion and the knee was extended, clinically relevant pressures were realized only when the hip was flexed to 90 degrees and the knee was fully extended. Pressures with the limbs in these positions were fifty-five millimeters of mercury (range 38 to 74 millimeters of mercury). RESULTS: With the hip held flexed to 90 degrees, statistically significantly increased intraneural pressures were measured as the knee was extended from 90 to 45 degrees of flexion (p = 0.048) and again from 45 to 0 degrees of flexion (p < or = 0.01). With the knee positioned in 45 degrees of flexion, statistically significantly increased intraneural pressures were measured as the hip was flexed from 45 to 90 degrees (p < or = 0.0062). When the knee was held fully extended, statistically significantly increased intraneural pressures were measured as the hip was flexed from 0 to 45 degrees of flexion (p = 0.0006) and again when the hip was brought from 45 to 90 degrees of flexion (p < or = 0.01). CONCLUSIONS: Intraneural sciatic nerve pressures are influenced by the position of the ipsilateral hip and knee. The magnitude of the pressure elevation appears to be related to the excursion of the nerve as the linear distance between the greater sciatic notch and the distal aspect of the leg increases. Intraneural tissue fluid pressures measured within a localized section of the sciatic nerve appeared to exceed published critical thresholds for alterations of blood flow and neural function only when the hip was flexed to 90 degrees and the knee was fully extended.

Adult↗
PubMed1999

The RNA export factor Gle1p is located on the cytoplasmic fibrils of the NPC and physically interacts with the FG-nucleoporin Rip1p, the DEAD-box protein Rat8p/Dbp5p and a new protein Ymr 255p.

Gle1p is an essential, nuclear pore complex (NPC)-associated RNA export factor. In a screen for high copy suppressors of a GLE1 mutant strain, we identified the FG-nucleoporin Rip1p and the DEAD-box protein Rat8p/Dbp5p, both of which have roles in RNA export; we also found Ymr255p/Gfd1p, a novel inessential protein. All three high copy suppressors interact with the C-terminal domain of Gle1p; immunoelectron microscopy localizations indicate that Gle1p, Rip1p and Rat8p/Dbp5p are present on the NPC cytoplasmic fibrils; Rip1p was also found within the nucleoplasm and on the nuclear baskets. In vivo localizations support the hypothesis that Rip1p contributes to the association of Gle1p with the pore and that Gle1p, in turn, provides a binding site for Rat8p/Dbp5p at the NPC. These data are consistent with the view that Gle1p, Rip1p, Rat8p/Dbp5p and Ymr255p/Gfd1p associate on the cytoplasmic side of the NPC to act in a terminal step of RNA export. We also describe a human functional homologue of Rip1p, called hCG1, which rescues Rip1p function in yeast, consistent with the evolutionary conservation of this NPC-associated protein.

Adenosine Triphosphatases↗
PubMed1999

Low-level transforming activity of an activated Ras gene under the control of a vaccinia virus p40 promoter is abrogated by truncation of the Ras cDNA.

Many human cancers have been shown to contain activated forms of the Ras proto-oncogene. Mutations comprising amino acid changes at codons 12, 13 and 61 therefore represent unique targets for cancer immunotherapy. Recombinant Vaccinia viruses encoding point mutated Ras oncogenes have raised issues concerning the safety and transforming ability of these recombinant vaccines. Vaccinia virus, a representative of the orthopox virus genus, is a large DNA virus that is cytopathogenic and that replicates in the cytoplasm of the infected cell. However, it remains unclear whether orthopox viruses are capable of genetic interactions with infected cells. Our studies show that DNA isolated from cells infected with a recombinant Vaccinia virus expressing mutated Ras constituted a poor reagent for transfection into NIH3T3 cells for transformation analysis. Stable integration of a recombinant Vaccinia virus expressing mutant Ras DNA was not detected in recipient cells. This study also demonstrates that the crossover plasmids used to generate the recombinant virus where the activated Ras gene is under the control of a Vaccinia virus early promoter had low but detectable transforming efficiency in the NIH3T3 transformation assay. Analysis of the transfected cells indicated that Ras transcription was initiated upstream of the Vaccinia virus promoter. The introduction of wobble mutations as well as the truncation of the Ras protein removed the transforming capabilities of the crossover vector. This study demonstrates the potential problems and solutions in the use of point mutated oncogenes in live vectors for cancer vaccine development.

3T3 Cells↗
PubMed1999

Prognostic models: evidence-based approach to predicting disease outcome.

BACKGROUND: A thorough understanding of the techniques underlying prognostic modelling, the potential shortcomings of prognostic models, and their applicability to dermatology are important for both clinicians and researchers. OBJECTIVE: This article distinguishes between prognostic and explanatory (causal) models, discusses some of the techniques used in developing a prognostic model, and addresses the importance of model generalizability. CONCLUSION: Prognostic models may be useful to the clinician, but must be used with care. It is important to critically appraise prognostic models and to assure that they are relevant to the population of interest. The ability to critically appraise prognostic models is predicated on a thorough understanding of the techniques used in their development and evaluation.

Decision Support Techniques↗
PubMed1999

Healing of diabetic neuropathic foot ulcers receiving standard treatment. A meta-analysis.

OBJECTIVE: The aim of the study was to determine the percentage of individuals with neuropathic diabetic foot ulcers receiving good wound care who heal within a defined period of time. RESEARCH DESIGN AND METHODS: We conducted a systematic review of the control groups of clinical trials that evaluated a treatment for diabetic neuropathic foot ulcers. The meta-analytic techniques used include an estimation of the weighted mean percentage healed by end point, an evaluation of the homogeneity of trials, and an estimate of the 95% CI of the grouped data. Grouped-data univariate and multivariate logistic regression was conducted to assess the impact of mean age, ulcer size, and duration on the percentage of ulcers healed at end point. RESULTS: We found a total of 10 control groups meeting our criteria. Six control groups used 20 weeks as the end point for healing or nonhealing. For the six control arms with a 20-week end point, we found a weighted mean healing rate of 30.9% (95% CI 26.6-35.1). A similar analysis for the four 12-week arms found a mean healing rate of 24.2% (19.5-28.8). We failed to detect any statistically significant heterogeneity for either the 20-week or the 12-week trials. CONCLUSIONS: After 20 weeks of good wound care, approximately 31% of diabetic neuropathic ulcers heal. Similarly, after 12 weeks of good care, approximately 24% of neuropathic ulcers attain complete healing. Further patient-level analyses are necessary to definitively determine the associations of age, wound size, and wound duration with likelihood of healing.

Diabetic Foot↗
PubMed1998

Oral immunization with enterocoated microbeads induces antigen-specific cytolytic T-cell responses.

A cytolytic T-lymphocyte (CTL) response has been generated to a protein antigen via oral administration in an experimental murine system. This was achieved by the formulation of the test antigen ovalbumin (OVA) in a pH-sensitive microsphere particle (microbead) with an acrylic-based coating to avoid its degradation by gastric enzymes. Comparative studies of orally administered enterocoated microbead-OVA particles, versus the more traditional formulation of OVA in adjuvant (DETOX-PC) given subcutaneously as immunogen, were conducted; both elicited comparable responses in the generation of antigen-specific lymphoproliferative and CTL responses. CTL lines generated via oral administration of antigen were shown to be CD3(+), CD4(-), and CD8(+). CTL lysis of OVA peptide-pulsed targets was shown to be inhibited by anti-CD8 antibody. Whereas oral administration of pH-sensitive enterocoated microbeads containing proteins has previously been shown to elicit antibody and lymphoproliferative T-cell responses to protein antigens, this is the first demonstration of the generation of an antigen-specific cytolytic T-cell response via oral administration of a protein immunogen formulated in such microbeads.

Administration, Oral↗
PubMed1998

Efficacy and prognostic value of simple wound measurements.

OBJECTIVES: To assess the association between planimetric wound area and simple wound measurements. To ascertain the applicability of planimetry-based research to clinical practice. DESIGN: A retrospective cohort study of 260 consecutive patients followed up for at least 24 weeks. SETTING: Outpatient dermatology department of a major medical center. INTERVENTION: Wounds were measured using computer-based planimetry and were treated according to a standard protocol for venous leg ulcers. PATIENTS: Two hundred sixty patients with venous leg ulcers. MAIN OUTCOME MEASURES: Complete ulcer healing at 24 weeks. RESULTS: Using the Pearson, Spearman, and Kendall correlation coefficients, we found a tight correlation between planimetric wound area and wound width, length, width x length, perimeter, and area based on the formula for an ellipse. The values for all correlation coefficients were greater than 0.80 (P < .001 for all associations). Width, length, length x width, and elliptical area measurements all correlated closely with failure to heal (P < .001). The correlation between simple values and planimetric area dropped considerably for wounds more than 40 cm2, which represented 6% of the wounds in this study. CONCLUSIONS: The equivalence between simple and planimetric wound measurements allows for the extrapolation of wound measurements from clinical trials to clinical practice, and suggests that simple wound measurements may confidently be used as predictors of healing in the clinical setting.

Dermatology↗
PubMed1998

Relationship of nm23 to proteolytic factors, proliferation and motility in breast cancer tissues and cell lines.

Low expression of the antimetastatic gene nm23 has been associated with shorter overall survival in breast cancer. To better understand the mechanism(s) of action of this protein, we compared the levels of the nm23 protein in 152 breast cancer samples with other factors known to be involved in metastasis or related to prognosis. There was no significant relationship between either of the nm23 isoforms and cathepsin D (Cat-D), urokinase plasminogen activator (uPA), its inhibitor (PAI-1), steroid hormone receptors or ploidy status. A marginal inverse correlation was observed between per cent S-phase and nm23-H1 expression (r = -0.193, P = 0.047) and a positive correlation was observed between uPA receptor (uPAR) and both nm23-H1 (r = 0.263, P = 0.0018) and nm23-H2 (r = 0.230, P = 0.0064). The nm23-H1 gene was transfected into MDA-MB-231 human breast cancer cells and 12 clones were selected, of which two were characterized extensively. We found no significant differences in Cat-D, uPA, PAI-1 or uPAR, as a function of nm23 expression in either the MDA-MB-231 cells or the transfected clones. Compared with the parent cell line, we did observe a dose-dependent decrease in growth factor-stimulated motility and a decrease in metastatic potential in two clones with four- and eightfold elevated nm23-H1 expression, whereas the proliferative activities were similar. We conclude that the decreased metastatic potential might be related to down-regulation of growth factor-stimulated motility.

Animals↗
PubMed1998

The use of a cationic liposome formulation (DOTAP) mixed with a recombinant tumor-associated antigen to induce immune responses and protective immunity in mice.

The cationic liposome DOTAP is a well-known transfection reagent. It has been manufactured and approved for clinical use, is readily available, and can be easily used as an adjuvant. These characteristics prompted us to investigate the effectiveness of DOTAP as an adjuvant to induce immune responses and protective immunity in mice using baculovirus-derived carcinoembryonic antigen (bV-CEA) as a model antigen. Two routes of administration and a dose-response study of bV-CEA were used in BALB/c mice to define the magnitude of the immune response as well as the most effective route of immunization. The results demonstrate differences in antibody titers, immunoglobulin (Ig)G isotype, and T-cell responses between the intravenous (i.v.) or subcutaneous (s.c.) route of immunization. The titer of the anti-CEA antibodies induced by the s.c. immunization was greater than the response by i.v. immunization. The s.c. route enhanced the IgG2a/2b isotype, whereas i.v. immunization elicited primarily IgG1. T-cell proliferation responses and cytokine production paralleled the humoral response (i.e., production was higher in the s.c. immunized animals). No differences in immunological responses were seen using either 25 or 10 microg of bV-CEA three times. An amount of 25 microg of bV-CEA/DOTAP given by s.c. immunization was sufficient in protecting mice from the transplant of syngeneic tumor cells transduced with the human CEA gene. We conclude that the cationic liposome DOTAP may be a useful immunoadjuvant for active anti-tumor immunotherapy in future clinical trials. This study will help to define the most effective way to use such an adjuvant.

Animals↗
PubMed1997

The yeast nucleoporin rip1p contributes to multiple export pathways with no essential role for its FG-repeat region.

The FG-repeat domain of the yeast Rip1 protein (Rip1p) was identified initially as a possible target for the nuclear export signal (NES) of the HIV-1 Rev protein in a yeast two-hybrid assay. Rip1p is inessential, associated with nuclear pore complexes, and structurally related to the FG-nucleoporin family of pore proteins. It contributes to HIV-1 Rev-mediated RNA export and is also important for the export of heat shock RNAs at 42 degrees C. We show here that Rip1p is essential for the export of heat shock RNAs, and this function is fulfilled by the unique carboxyl terminus of Rip1p with no substantial contribution from the FG-repeat region. Genetic interactions between Rip1p and the RNA export mediator Gle1p are described, which support a role of the carboxyl terminus of Rip1p in poly(A)+ RNA export. Finally, this domain of Rip1p also contributes to Rev-mediated RNA export. The data suggest that Rip1p promotes the nuclear export of different classes of substrates by contributing to optimal pore function.

Amino Acid Sequence↗