PubMed Health⌕ Search

Biomedical subjects

Helen Kim

Publications and source records attributed to Helen Kim.

13 recordsLinked to original sources
PubMed2004

Nutriproteomics: identifying the molecular targets of nutritive and non-nutritive components of the diet.

The study of whole patterns of changes in protein expression and their modifications, or proteomics, presents both technological advances as well as formidable challenges to biological researchers. Nutrition research and the food sciences in general will be strongly influenced by the new knowledge generated by the proteomics approach. This review examines the different aspects of proteomics technologies, while emphasizing the value of consideration of "traditional" aspects of protein separation. These include the choice of the cell, the subcellular fraction, and the isolation and purification of the relevant protein fraction (if known) by protein chromatographic procedures. Qualitative and quantitative analyses of proteins and their peptides formed by proteolytic hydrolysis have been substantially enhanced by the development of mass spectrometry technologies in combination with nanoscale fluidics analysis. These are described, as are the pros and cons of each method in current use.

Animals↗
PubMed2004

Oral fludarabine has significant activity in patients with previously untreated chronic lymphocytic leukemia, and leads to increased STAT1 levels in vivo.

Fifteen patients with previously untreated chronic lymphocytic leukemia (CLL) were treated with oral fludarabine. Toxicities were mainly hematologic, and the response rate was 80%. To assess the effect of fludarabine on the transcription factor STAT1, blood samples obtained on study entry were treated in vitro with fludarabine for 24 h, and the majority of samples displayed an expected decrease in STAT1. To determine whether similar changes occurred in vivo, we developed a flow cytometric assay to quantitate STAT1 levels. On completion of fludarabine cycle 1, CLL cells showed increased STAT1 in the majority of patients, in contrast to the in vitro findings. This may reflect a survival advantage for cells that express high levels of STAT1. In conclusion, oral fludarabine is highly active and merits further investigation in previously untreated patients with CLL. Larger studies are indicated to determine optimal timing of STAT1 assessment, and if changes in STAT1 represent an in vivo indicator of response to purine analog therapy.

Administration, Oral↗
PubMed2003

The UAB Proteomics Database.

SUMMARY: The University of Alabama at Birmingham (UAB) Proteomics Database (UPD) (http://www.uab.edu/proteinmenu) was created to provide a repository for the storage and linkage of two-dimensional (2D) gel images and the associated information obtained through mass spectrometry analysis of the proteins excised from the 2D gels in a manner similar to the SWISS-2DPAGE database and the Stanford Microarray Database. This was accomplished through the development of a web interface, a relational database, image maps and hyperlinks stored in the database. In addition to the internally generated data, UPD provides links to the National Center for Biotechnology Information via accession number hyperlinks. UPD currently contains information on 44 individual proteins derived from four experiments conducted by four UAB faculty members. Images of the gels from which each of these proteins was isolated are accessed by hyperlinks embedded in the database. AVAILABILITY: The UAB Proteomics Database can be accessed at http://www.uab.edu/proteinmenu.

Alabama↗
PubMed2003

Gemcitabine added to doxorubicin, bleomycin, and vinblastine for the treatment of de novo Hodgkin disease: unacceptable acute pulmonary toxicity.

BACKGROUND: Gemcitabine is an effective treatment for recurrent Hodgkin disease (HD), with relatively minimal associated toxicity. The authors conducted a trial substituting this drug for dacarbazine in the standard regimen to form ABVG (doxorubicin, bleomycin, vinblastine, gemcitabine) for patients with newly diagnosed, high-risk HD. METHODS: Twelve patients (median age, 34 years) with advanced-stage de novo HD were enrolled. Standard doses of doxorubicin, bleomycin, and vinblastine were given for six cycles. Cohorts of three patients were enrolled and the dose of gemcitabine was escalated to identify the maximally tolerated dose in this combination. RESULTS: The maximally tolerated dose of gemcitabine was determined to be 800 mg/m(2) in this combination. Five patients developed clinically significant pulmonary toxicity. Three required hospitalization during the final two cycles of treatment. Pneumonitis could not be predicted with serial diffusion capacity for carbon monoxide (DECO) evaluations, and reversed after discontinuation of bleomycin in three patients and steroid therapy in two patients. All 12 patients are alive to date, and 4 patients have experienced disease progression. CONCLUSIONS: The bleomycin/gemcitabine combination should not be pursued for de novo HD due to significant pulmonary toxicity.

Adult↗
PubMed2003

Association of aortic atherosclerosis with cerebral beta-amyloidosis and learning deficits in a mouse model of Alzheimer's disease.

High fat/high cholesterol diets exacerbate beta-amyloidosis in mouse models of Alzheimer's disease (AD). It has been impossible, however, to study the relationship between atherosclerosis and beta-amyloidosis in those models because such mice were on atherosclerosis-resistant genetic backgrounds. Here we report the establishment of AD model mice, B6Tg2576, that are prone to atherosclerosis. B6Tg2576 mice were produced by back-crossing Tg2576 mice, an AD mouse model overexpressing human amyloid beta-protein precursor with the Swedish double mutation, to C57BL/6 mice, a strain susceptible to diet-induced atherosclerosis. An atherogenic diet induced aortic atherosclerosis and exacerbated cerebral beta-amyloidosis in B6Tg2576 mice. Compared with age-matched non-transgenic littermates, B6Tg2576 mice developed significantly more diet-induced aortic atherosclerosis. Unexpectedly, normal diet-fed B6Tg2576 mice also developed fatty streak lesions (early atherosclerosis) in the aorta. The aortic atherosclerotic lesion area positively correlated with cerebral beta-amyloid deposits in B6Tg2576 mice on both atherogenic and normal diets. Furthermore, behavioral assessments demonstrated that B6Tg2576 mice fed an atherogenic diet had more spatial learning impairment than those fed a normal diet. Our results suggest that synergistic mechanisms may be involved in the pathogenesis of atherosclerosis and AD. These findings may have important implications in the prevention and treatment of cardiovascular diseases as well as AD.

Aging↗
PubMed2003

Family history of diabetes as a potential public health tool.

Given the substantial morbidity and mortality associated with type 2 diabetes, it is important that public health seek ways to delay or prevent the onset of this condition. Risk factors for type 2 diabetes are well established and include underlying genetic susceptibility. Despite this knowledge, as well as significant advances in understanding the human genome, the prevalence of type 2 diabetes continues to rise at an alarming rate. Because type 2 diabetes is a complex condition involving a combination of genetic and environmental factors, DNA testing for susceptibility genes is not yet warranted. However, because family history reflects genetic susceptibility in addition to other factors, it may be a useful public health tool for disease prevention. When evaluating family history as a public health tool, several important issues need to be considered, including the analytic and clinical validity and the clinical utility of using family history as a screening tool. These issues as well as a review of the epidemiologic evidence evaluating family history as a risk factor will be reviewed.Overall, a family history approach appears to be a promising new public health tool to fight the growing epidemic of diabetes in the United States. Adequate levels of funding to further evaluate this approach and to develop appropriate tools should be made available for research activities focused on this important area.

Diabetes Mellitus, Type 2↗
PubMed2003

DING, a genistein target in human breast cancer: a protein without a gene.

Because most noncancer cells are tolerant to high micromolar concentrations of genistein (GEN), inhibitory or stimulatory effects of GEN have been claimed for a wide variety of biochemical targets that lead to a plethora of potential mechanisms. However, because GEN is present in tissues in the nanomol-per-liter range, most of these mechanisms are unlikely to be relevant in vivo. To better identify proteins that are targets of GEN, we used a GEN-agarose-affinity phase. Cytosols from human breast cancer MCF-7 cells were fractionated over a Sephadex diethylaminoethyl column, and nonabsorbed proteins in the flow-through were affinity absorbed onto a 2-carboxygenistein-agarose column. After proteins were washed with 100 mmol NaCl/L to remove weakly bound proteins, affinity elution was conducted with 1 mmol 2-carboxygenistein/L. Using this method, a p38 protein was recovered from MCF-7 cells. N-terminal chemical sequencing of the first 30 residues of the protein revealed a peptide sequence similar to those that have been discovered in human tissues (a T-cell attractant protein from synovial fluid from patients with osteoarthritis and an analogous human skin fibroblast protein using a hirudin-affinity column) as well as a cotonine-binding protein from rat brain and related proteins in plants. In each case, the corresponding gene has not been found. In conclusion, although much of the human genome has been sequenced, novel proteins that are not described by genome data remain to be found. The DING protein (N-terminal amino acid sequence Asp-Ile-Asn-Gly) that binds to genistein with high affinity is one of these. Its biological role, however, remains to be defined.

Animals↗
PubMed2002

Intravenous home hydration in pediatric patients following adenotonsillectomy.

OBJECTIVE: To determine the feasibility, safety and efficacy of intravenous home hydration for pediatric postoperative adenotonsillectomy patients. METHOD: Nonrandomized control trial of two groups of pediatric patients following adenotonsillectomy--one with (H) and one without postoperative home intravenous hydration (WH). SETTING: A tertiary care, university-based children's hospital. INTERVENTION: Administration of 25 cm3 kg-1 of Lactated Ringer's solution once a day for 3 days via an intravenous catheter. RESULTS: Three of 22 patients in the (WH) group and none of the 25 patients in the (H) group required an emergency room admission for dehydration. Difficulty swallowing and activity level were found to be statistically different based on chi2-analysis (P<0.05). The hydration group (H) had a greater swallowing difficulty score (1.4) compared with the nonhydration (WH) group (0.06). The (H) group had a lower activity score (0.2) compared with the (WH) group. Other parameters such as duration of pain, the severity of pain, days until oral feeds could be taken without difficulty, degree of dysphagia, degree of neck, throat, tongue and ear pain were not statistically different between the two groups based on chi2-analysis (P<0.05). There were no complications associated with intravenous hydration. CONCLUSION: Increased efficacy from intravenous hydration was not shown based on a number of parameters. Selected patients with a high likelihood to develop dehydration or medically intractable emesis may benefit from intravenous hydration and may avoid emergency room or hospital admission. Bolus infusions of 25 cm3 kg-1 of Lactated Ringer's solution by home care nursing can be implemented safely in pediatric patients.

Adenoidectomy↗
PubMed2002

High throughput two-dimensional blue-native electrophoresis: a tool for functional proteomics of mitochondria and signaling complexes.

The recent upsurge in proteomics research has been facilitated largely by streamlining of two-dimensional (2-D) gel technology and the parallel development of facile mass spectrometry for analysis of peptides and proteins. However, application of these technologies to the mitochondrial proteome has been limited due to the considerable complement of hydrophobic membrane proteins in mitochondria, which precipitate during first dimension isoelectric focusing of standard 2-D gels. In addition, functional information regarding protein:protein interactions is lost during 2-D gel separation due to denaturing conditions in both gel dimensions. To resolve these issues, 2-D blue-native gel electrophoresis was applied to the mitochondrial proteome. In this technique, membrane protein complexes such as those of the respiratory chain are solubilized and resolved in native form in the first dimension. A second dimension sodium dodecyl sulfate-polyacrylamide gel electrophoresis gel then denatures the complexes and resolves them into their component subunits. Refinements to this technique have yielded the levels of throughput and reproducibility required for proteomics. By coupling to tryptic peptide fingerprinting using matrix-assisted laser desorption/ionization-time of flight mass spectrometry, a partial mitochondrial proteome map has been assembled. Applications of this functional mitochondrial proteomics method are discussed.

Animals↗
PubMed2002

Effective purging of autologous hematopoietic stem cells using anti-B-cell monoclonal antibody-coated high-density microparticles prior to high-dose therapy for patients with non-Hodgkin's lymphoma.

Contamination of hematopoietic stem cells (HSCs) with tumor cells has been associated with increased incidence of relapse in patients with non-Hodgkin's lymphoma following autologous HSC transplantation. Effective purging of tumor cells may improve the results of HSC transplantation, but current methods of purging are technically difficult to perform with large numbers of cells and do not consistently remove all detectable cells. We report a pilot clinical trial in which 10 patients with relapsed B-cell non-Hodgkin's lymphoma received high-dose chemotherapy followed by infusion of autologous HSCs depleted of B-cells by high-density microparticles (HDM) coated with anti-CD19 and anti-CD20 monoclonal antibodies (BCell-HDM). HSCs were mobilized with cyclophosphamide and granulocyte colony-stimulating factor. In 6 of the 10 patients, B-cells were detectable by immunocytochemical analysis of the apheresis products prior to treatment. Following treatment with the BCell-HDM, no B-cells were detected in the products from 5 of these patients, a result representing a median depletion of >2.2 logs (range, >0.4 to >5.1 logs). The median recovery of nontarget cells postdepletion was 73% for CD34 cells and 78% for CD3+ cells. All patients received high-dose cyclophosphamide, BCNU (carmustine), and etoposide prior to reinfusion of their B-cell-depleted autologous HSCs. The median number of CD34+ cells cryopreserved was 3.6 x 10(6) cells/kg (range, 2.2-10.1 x 10(6) cells/kg). Engraftment was rapid in all cases, with a median time to achieve an absolute neutrophil count of 0.5 x 10(9)/L of 10 days (range, 8-11 days). The median time to achieve a platelet count of 20 x 10(9)/L unsupported by platelet transfusion was 11.5 days (range, 8-17 days). This nonmagnetic negative-depletion technology is simple, rapid, and effective in depleting target cells to undetectable levels, with excellent recovery of nontarget cells.

Adult↗