Search PubMed⌕ Search

Biomedical subjects

D Lee

Publications and source records attributed to D Lee.

At least 217 records · Page 12Linked to original sources
PubMed1999

Control of 3' splice site choice in vivo by ASF/SF2 and hnRNP A1.

The constitutive splicing factor ASF/SF2 has been shown to affect the choice between alternative splice sites by favoring the proximal as opposed to the distal choice. HnRNP A1 antagonizes ASF/SF2 by promoting the distal choice for competing 5' splice sites. We have tested the in vivo effects of these proteins on alternative 3' splice site choices. Cotransfection of a dihydrofolate reductase-calcitonin chimeric construct togetherwith a plasmid specifying the SR protein ASF/SF2 into cells of several mammalian lines increased use of a proximal 3' splice site, resulting in the inclusion of a terminal calcitonin exon. This stimulation of 3' proximal splicing was antagonized by cotransfection with an hnRNP A1 plasmid. This effect of hnRNP A1 in promoting distal splicing was also seen in an hnRNP A1-deficient MEL cell line. A similar effect of hnRNP A1 was demonstrated with mutant hamster adenine phosphoribosyltransferase (aprt) transcripts that are normally constitutively spliced, suggesting that hnRNP A1 may be a general inhibitor of proximal splicing. Intron size also influenced splice site choice in mutant aprt transcripts, with larger introns favoring proximal splicing. These results support the idea that the ratios of particular but general splicing factors and hnRNPs play a role in alternative splicing.

3' Untranslated Regions↗
PubMed1999

Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments.

Although recent studies have indicated that the major histocompatibility complex-like, beta2-microglobulin-associated CD1 molecules might function to present a novel chemical class of antigens, lipids and glycolipids, to alpha/beta T cells, little is known about the T cell subsets that interact with CD1. A subset of CD1d-autoreactive, natural killer (NK)1.1 receptor-expressing alpha/beta T cells has recently been identified. These cells, which include both CD4(-)CD8(-) and CD4(+) T cells, preferentially use an invariant Valpha14-Jalpha281 T cell receptor (TCR) alpha chain paired with a Vbeta8 TCR beta chain in mice, or the homologous Valpha24-JalphaQ/Vbeta11 in humans. This cell subset can explosively release key cytokines such as interleukin (IL)-4 and interferon (IFN)-gamma upon TCR engagement and may regulate a variety of infectious and autoimmune conditions. Here, we report the existence of a second subset of CD1d-restricted CD4(+) T cells that do not express the NK1.1 receptor or the Valpha14 TCR. Like the Valpha14(+) NK1.1(+) T cells, these T cells exhibit a high frequency of autoreactivity to CD1d, use a restricted albeit distinct set of TCR gene families, and contribute to the early burst of IL-4 and IFN-gamma induced by intravenous injection of anti-CD3. However, the Valpha14(+) NK1.1(+) and Valpha14(-) NK1.1(-) T cells differ markedly in their requirements for self-antigen presentation. Antigen presentation to the Valpha14(+) NK1.1(+) cells requires endosomal targeting of CD1d through a tail-encoded tyrosine-based motif, whereas antigen presentation to the Valpha14(-) NK1.1(-) cells does not. These experiments suggest the existence of two phenotypically different subsets of CD1d-restricted T cells that survey self-antigens loaded in distinct cellular compartments.

Animals↗
PubMed1999

Oropharyngeal manifestations of lepidopterism.

OBJECTIVE: To describe previously unreported oropharyngeal manifestations and management of caterpillar ingestion. DESIGN: Retrospective case series. SETTING: Tertiary children's hospital. PATIENTS: A total of 733 cases of exposure to caterpillars from January 1, 1994, to November 1, 1997, were reviewed. Twenty-six patients had oropharyngeal exposure with 8 patients ingesting the caterpillar. Ages ranged from 7 months to 7 years with 14 boys and 12 girls. INTERVENTIONS: All patients had a thorough examination of the oropharynx for caterpillar spines. For children who ingested a caterpillar, direct laryngoscopy, bronchoscopy, and esophagoscopy with removal of caterpillar spines were performed. RESULTS: At the point of caterpillar contact, buried caterpillar spines with focal erythema were observed. The lips, tongue, and buccal mucosa were the most frequently involved areas. The esophagus was involved in 8 of the patients. No postoperative complications were noted. CONCLUSION: With individualized care and prompt removal of venomous caterpillar spines, complications are not likely to result from caterpillar ingestion.

Animals↗
PubMed1999

E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer.

To extend earlier observations of germline E-cadherin mutations in kindreds with an inherited susceptibility to diffuse gastric cancer, we searched for germline E-cadherin mutations in five further families affected predominantly by diffuse gastric cancer and one family with a history of diffuse gastric cancer and early-onset breast cancer. Heterozygous inactivating mutations were found in the E-cadherin gene in each of these families. No mutation hotspots were identified. These results demonstrate that germline mutation of the E-cadherin gene is a common cause of hereditary diffuse gastric cancer and suggest a role for these mutations in the incidence of breast cancer.

Adenocarcinoma↗
PubMed1999

Update on sequential isologous rat organ transplantation: pancreaticoduodenal and kidney transplantations.

This periodic report includes intermittent results of consecutive pancreaticoduodenal (Pd) and kidney (Kt) transplants in inbred rats and results on double kidney transplants that did not follow sequential transplant protocol. Eight 24-month-old Lewis pancreas, kidney, and aorta served histological controls showing normal histological architecture with no atherosclerosis developed in the aorta. Thirty-four month old pancreas and thirty-two month old kidneys, which resided in young hosts for at least three occasions, appeared as youthful Pd and Kt grafts. They show normal histological appearance for more than the expected life span of a Lewis rat. The fact that not only pancreases but also kidneys outlived their host leads to the study of other different organs' viability as aged valuable grafts. Nevertheless, the threats by the development of atherosclerosis in graft-associated aortas resulted in slow progression of the follow-ups.

Animals↗
PubMed1999

Diagnosis of carpal tunnel syndrome. Ultrasound versus electromyography.

This article presents a new technique for diagnosing carpal tunnel syndrome using ultrasound. The ultrasound characteristics of the normal and abnormal median nerve are discussed in relation to carpal tunnel syndrome. The development of ultrasound as a new diagnostic modality for carpal tunnel syndrome is presented in a three-part study correlating the ultrasound measurements of the median nerve and electromyogram of the median nerve. A new algorithm for evaluating patients with carpal tunnel syndrome is presented.

Adult↗
PubMed1999

Static disease on anastrozole provides similar benefit as objective response in patients with advanced breast cancer.

BACKGROUND: This paper reports on the clinical relevance of durable static disease (SD) (> or = 24 weeks) in breast cancer patients treated with the aromatase inhibitor anastrozole. PATIENTS AND METHODS: All patients were part of two prospective, randomised, multicentre studies in postmenopausal women with advanced disease in which megestrol acetate was compared with anastrozole 1 mg. Survival from initiation of treatment was analysed by the response type, i.e., complete response (CR)/partial response (PR), static disease (SD) (> or = 24 weeks), or progressive disease (PD), achieved on therapy. RESULTS: Median survival with anastrozole 1 mg was similar between patients who obtained CR/PR and SD (> or = 24 weeks). Similarly, no difference in survival was observed in patients treated with megestrol acetate who achieved CR/PR and SD. With both treatments patients with CR/PR and SD had improved survival over those patients with PD within 24 weeks. There was no difference between treatment arms for patients showing PD within 24 weeks. CONCLUSIONS: These data confirm that durable SD (> or = 24 weeks) is a clinically useful remission criterion in postmenopausal women with advanced breast cancer with predictive value for overall survival. It also confirms the value of this endpoint with anastrozole, a new generation aromatase inhibitor.

Anastrozole↗
PubMed1999

Self-expandable metal stents for malignant dysphagia.

BACKGROUND: The use of self-expandable metal stents in relieving dysphagia for patients with incurable malignant oesophageal strictures was retrospectively evaluated. METHODS: Between September 1993 and August 1996, 66 male and 16 female patients with a median age of 72 years received self-expandable metal stents for malignant dysphagia. Six patients had concurrent tracheo-oesophageal fistulas. All patients were stented under sedation and stent insertion was performed under fluoroscopic guidance. RESULTS: Stent placement was successful in 80 patients (98%). There were seven early complications (inaccurate positioning (n = 3), migration (n = 1), incomplete expansion (n = 1), intractable pain (n = 1), and perforation (n = 1)). Two complications were lethal and three were treated endoscopically. Mean dysphagia grade improved from 3.2+/-0.7 to 1.8+/-0.9 (P < 0.05) after implantation. All tracheo-esophageal fistulas were successfully occluded. Upon a median follow-up of 8 weeks (range: 2-20 weeks), 30 complications developed in 21 patients (tumour overgrowth (n = 15), food bolus obstruction (n = 7), tumour ingrowth (n = 2), buckling of stent (n = 2), tracheo-esophageal fistula (n = 2), bleeding (n = 1), and gastric wall herniation through metal coils (n = 1)). Median survival was 13 weeks (range: 1-82 weeks). CONCLUSION: Self-expandable metal stents provide useful palliation in patients with incurable malignant dysphagia.

Adenocarcinoma↗
PubMed1999

Hydroxyurea-induced nail pigmentation in HIV patients.

Hydroxyurea (HU), a cytotoxic agent used in myeloproliferative disorders, has recently been introduced as an adjunct to combination anti-retroviral therapy. We describe abnormal nail pigmentation in four HIV-seropositive patients treated with HU and discuss the likely factors associated with its development.

Adult↗
PubMed1999

Long-term results of dermal grafting for the repair of nasal septal perforations.

The closure of nasal septal perforations is a significant surgical challenge with a high failure rate. Dermis placed between mucoperichondrial advancement flaps may be an alternative. The usefulness of dermal grafting for the repair of nasal septal perforations was initially investigated in an animal model. Four pigs had 1.5 x 2.5 cm perforations surgically created and closed with either temporalis fascia or dermis placed under a local mucoperichondrial flap. The dermal graft group had an average closure of 80% with histologically normal mucosal surfaces. The temporalis fascia group had no closure. Fourteen patients with chronic nasal septal perforations from iatrogenic causes, trauma, and drug abuse were repaired with dermal grafting. Nine patients had complete closure, 3 patients had partial closures, and 1 patient's graft dislodged on the first postoperative day. Dermal grafts placed between mucoperichondrial flaps are a viable alternative for the closure of nasal septal perforations.

Adult↗
PubMed1999

Cytokine molecular adjuvants modulate immune responses induced by DNA vaccine constructs for HIV-1 and SIV.

DNA or nucleic acid immunization has been shown to induce both antigen-specific cellular and humoral immune responses in vivo. Moreover, immune responses induced by DNA immunization can be enhanced and modulated by the use of molecular adjuvants. To further engineer the immune response in vivo, we investigated the induction and regulation of immune responses from the codelivery of Thl cytokines (interleukin-2 [IL-2] and IL-12), Th2 cytokines (IL-4 and IL-10), and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes along with a DNA vaccine construct encoding for simian immunodeficiency virus (SIV) gag/pol proteins. We observed that coinjection with IL-2, IL-4, IL-10, and GM-CSF resulted in increased levels of antigen-specific antibodies. In addition, we found that coinjection with cytokine genes drove the immune responses toward a more Thl or Th2 phenotype. We also observed that coadministration of IL-2, IL-12, and GM-CSF genes resulted in a dramatic enhancement of Th proliferation responses. Moreover, coimmunization with IL-12 genes resulted in a dramatic enhancement of antigen-specific cytotoxic T lymphocyte (CTL) responses. These results support the potential utility of molecular adjuvants in DNA vaccine regimens.

Adjuvants, Immunologic↗
PubMed1999

Plutonium fecal and urinary excretion functions: derivation from a systemic whole-body retention function.

Liver-bile secretion directly influences the content of plutonium in feces. To assess the reliability of plutonium metabolic models and to improve the accuracy of interpreting plutonium fecal data, we developed a compartmental model that simulates the metabolism of plutonium in humans. With this model, we can describe the transport of plutonium contaminants in the systemic organs and tissues of the body, including fecal and urine excretions, without using elaborate kinetic information. The parameter values of the models, which describe the translocation rates and recycling of plutonium in the body, can be derived from a multi-term exponential systemic function for whole-body retention. The analytical derivations and algorithms for solving translocation parameter values are established for the model and illustrated by applying them to the biokinetics and bioassay of plutonium. This study describes how to (1) design a physiological model for incorporating liver biliary secretion and for obtaining a fecal-excretion function, (2) develop an analytical solution for identifying the translocation-parameter values incorporating the recycling of plutonium in the body, and (3) derive a set of urinary and fecal excretion-functions from a published systemic whole-body retention function, generally acknowledged to be accurate, as a real and practical example.

Algorithms↗
PubMed1999

Cochlear reimplantation.

OBJECTIVE: A small number of multichannel cochlear implant (CI) recipients require reimplantation. This study describes the causes of failure, surgical technique, and hearing outcomes in a consecutive series of 16 patients undergoing reimplantation of multichannel devices. We hypothesize that reimplantation is safe and that hearing results are at least as good as those measured following primary implantation. STUDY DESIGN: Retrospective analysis of consecutive clinical series. METHODS: Chart analysis of 191 consecutive CI operations performed at the University of Miami Ear Institute between 1990 and 1997 revealed 16 patients who received a second multichannel device. All but one had a minimum follow-up of 1 year after reimplantation. Ten of these patients had initial implantation performed by us, and six were initially operated on elsewhere. Main outcomes of the initial procedure were compared with those of the reimplantation, including electrode insertion length, number of channels programmed, and audiometric results. In addition, cause of failure and relevant surgical findings at the second procedure are described. RESULTS: There were no surgical complications after reimplantation surgery. Device failure was the most frequent cause for reimplantation. Time between initial implantation and failure ranged from 0 to 46 months (mean, 22.4 mo; median, 23 mo). Common intraoperative findings include mastoid fibrosis, bone growth at the cochleostomy, and skin flap breakdown. Following reimplantation, mean length of insertion, number of channels actively programmed, and speech recognition scores were at least as good as findings before initial implant failure. CONCLUSION: CI reimplantation is safe and effective.

Adolescent↗
PubMed1999

A meta-analysis of swimming and water precautions.

OBJECTIVE: To reconcile conflicting reports concerning the incidence of otorrhea in children with tympanostomy tubes who swim without ear protection. STUDY SELECTION: Articles were identified by MEDLINE search, Current Contents, and references from review articles, textbook chapters, and retrieved reports. Controlled trials of water precautions following tympanostomy tube placement were selected by independent observers and scored on 10 measures of study validity. Five English-language articles met all inclusion criteria. DATA EXTRACTION: Data were abstracted for an endpoint of otorrhea following swimming without ear protection with a minimum follow-up of 6 weeks. DATA SYNTHESIS: Pooled analysis of 619 children revealed a rate difference of -5.04 (95% confidence interval [CI], -11.62 to 1.54). No significant difference in the incidence of otorrhea was noted between patients who swam without ear protection and nonswimmers. CONCLUSION: There is no increase in incidence of otorrhea in children who swim without ear protection compared with children who do not swim following tympanostomy tube placement.

Cerebrospinal Fluid Otorrhea↗