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Helen Kim

Publications and source records attributed to Helen Kim.

At least 37 records · Page 2Linked to original sources
PubMed2004

Proteomics analysis of rat brain protein modulations by grape seed extract.

Dietary supplements such as grape seed extract (GSE) enriched in proanthocyanidins (PA) (oligomeric polyphenols) have been suggested to have multiple health benefits, due to antioxidant and other beneficial activities of the PA. However, a systematic analysis of the molecular basis of these benefits has not been demonstrated. Because the brain is vulnerable to age-related oxidative damage and other insults including inflammation, it was hypothesized that rats ingesting GSE would experience changes in expression or modifications of specific brain proteins that might protect against pathologic events. Normal adult female rats were fed diets supplemented with 5% GSE for 6 weeks. Proteomics analysis (2D electrophoresis and mass spectrometry) of brain homogenates from these animals identified 13 proteins that were altered in amount and/or charge. Because many of these changes were quantitatively in the opposite direction from previous findings for the same proteins in either Alzheimer disease or mouse models of neurodegeneration, the data suggest that these identified proteins may mediate the neuroprotective actions of GSE. This is the first identification and quantitation of specific proteins in mammalian tissues modulated by a dietary supplement, as well as the first to demonstrate links of such proteins with any disease.

Amino Acid Sequence↗
PubMed2004

Immunization of Alzheimer model mice with adenovirus vectors encoding amyloid beta-protein and GM-CSF reduces amyloid load in the brain.

Induction of anti-amyloid beta-protein (Abeta) antibodies in transgenic mouse models of Alzheimer disease (AD) by repeated injection of synthetic Abeta was shown to be effective in preventing and removing deposition of Abeta aggregates in the brain. Here, we have tested a non-invasive modality whereby a replication-defective adenovirus vector encoding Abeta was intranasally administered to mice to elicit immune responses against Abeta. Intranasal immunization only with the adenovirus vector failed to induce significant immune responses. When an adenovirus vector encoding granulocyte/macrophage-colony stimulating factor (GM-CSF) was used as an adjuvant in conjunction with the adenovirus encoding Abeta, a marked immune response was elicited against Abeta. Immunoglobulin isotyping revealed that the induced anti-Abeta antibodies are predominantly of the IgG2b and IgG1 isotypes, suggesting a Th-2 anti-inflammatory type. Furthermore, amyloid load in the brain of AD model mice (Tg2576) vaccinated with adenovirus vectors encoding Abeta and GM-CSF was much smaller than that in control Tg2576 mice. Thus, intranasal administration of adenovirus vectors encoding Abeta and GM-CSF may be effective in prevention and treatment of AD.

Adenoviridae↗
PubMed2004

Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin lymphoma: increased interferon-alpha/beta-inducible gene expression, without significant toxicity.

CpG oligodeoxynucleotides (CpG-ODNs) affect innate and adaptive immune responses, including antigen presentation, costimulatory molecule expression, dendritic cell maturation, and induction of cytokines enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). We conducted a phase 1 study evaluating 4 dose levels of a CpG-ODN (1018 ISS) with rituximab in 20 patients with relapsed non-Hodgkin lymphoma (NHL). Patients received CpG once a week for 4 weeks beginning after the second of 4 rituximab infusions. Adverse events were minimal. Quantitative polymerase chain reaction (PCR) measurements of a panel of genes inducible by CpG-ODN and interferons were performed on blood samples collected before and 24 hours after CpG. A dose-related increase was measured in the expression of several interferon-inducible genes after CpG and correlated with serum levels of 2'-5' oligoadenylate synthetase (OAS), a validated interferon response marker. Genes induced selectively by interferon-gamma (IFN-gamma) were not significantly induced by CpG. In conclusion, we have defined a set of gene expression markers that provide a sensitive measure of biologic responses of patients to CpG therapy in a dose-related manner. Moreover, all the genes significantly induced by this CpG are regulated by type 1 interferons, providing insight into the dominant immune mechanisms in humans. CpG treatment resulted in no significant toxicity, providing rationale for further testing of this exciting combination immunotherapy approach to NHL.

Adult↗
PubMed2004

Limited T cell receptor diversity of HCV-specific T cell responses is associated with CTL escape.

Escape mutations are believed to be important contributors to immune evasion by rapidly evolving viruses such as hepatitis C virus (HCV). We show that the majority of HCV-specific cytotoxic T lymphocyte (CTL) responses directed against viral epitopes that escaped immune recognition in HCV-infected chimpanzees displayed a reduced CDR3 amino acid diversity when compared with responses in which no CTL epitope variation was detected during chronic infection or with those associated with protective immunity. Decreased T cell receptor (TCR) CDR3 amino acid diversity in chronic infection could be detected long before the appearance of viral escape mutations in the plasma. In both chronic and resolved infection, identical T cell receptor clonotypes were present in liver and peripheral blood. These findings provide a deeper understanding of the evolution of CTL epitope variations in chronic viral infections and highlight the importance of the generation and maintenance of a diverse TCR repertoire directed against individual epitopes.

Amino Acid Sequence↗
PubMed2004

Modification of the mitochondrial proteome in response to the stress of ethanol-dependent hepatotoxicity.

Mitochondria are particularly susceptible to increased formation of reactive oxygen and nitrogen species in the cell that can occur in response to pathological and xenobiotic stimuli. Proteomics can give insights into both mechanism of pathology and adaptation to stress. Herein we report the use of proteomics to evaluate alterations in the levels of mitochondrial proteins following chronic ethanol exposure in an animal model. Forty-three proteins showed differential expression, 13 increased and 30 decreased, as a consequence of chronic ethanol. Of these proteins, 25 were not previously known to be affected by chronic ethanol emphasizing the power of proteomic approaches in revealing global responses to stress. Both nuclear and mitochondrially encoded gene products of the oxidative phosphorylation complexes in mitochondria from ethanol-fed rats were decreased suggesting an assembly defect in this integrated metabolic pathway. Moreover mtDNA damage was increased by ethanol demonstrating that the effects of ethanol consumption extend beyond the proteome to encompass mtDNA. Taken together, we have demonstrated that chronic ethanol consumption extends to a modification of the mitochondrial proteome far broader than realized previously. These data also suggest that the response of mitochondria to stress may not involve non-discriminate changes in the proteome but is restricted to those metabolic pathways that have a direct role in a specific pathology.

Alcohol Drinking↗
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

Family history as a risk factor for stroke in young women.

BACKGROUND: Family history of stroke (FHS) is associated with risk of stroke in middle-aged to elderly populations. However, few studies have examined this association in younger women or by stroke type. A population-based, case-control study was conducted to examine the association of FHS and risk of stroke in young women, and to determine whether the association is independent of other stroke risk factors. METHODS: Cases were women aged 18 to 44 years, with first, nonfatal ischemic (n =49) and hemorrhagic (n = 63) strokes in western Washington State in 1991 to 1995. Demographically similar community controls (n = 446) were identified through random-digit telephone dialing. Information on FHS in first-degree relatives (parents and siblings) and other risk factors was obtained through an interview. Person-years (P-Y) at risk of stroke for relatives of each subject were included in polytomous logistic regression models to adjust for family size. The analysis was conducted between 1999 and 2000. RESULTS: After adjustment for age and P-Y, FHS in first-degree relatives was significantly associated with an increased risk of hemorrhagic (odds ratio [OR]=2.6, 95% confidence interval [CI]=1.5-4.3) and ischemic stroke (OR=2.1, 95% CI=1.2-3.9). FHS remained associated with risk of hemorrhagic stroke (OR=2.4, 95% CI=1.4-4.1) and ischemic stroke (OR=1.8, 95%CI=0.9-3.5) after further adjustment for diabetes, hypertension, hypercholesterolemia, body mass index, physical activity, smoking, alcohol, and family history of myocardial infarction. Findings were similar when associations with parental and sibling FHS were examined separately. CONCLUSIONS: Family history of stroke is a risk factor for both hemorrhagic and ischemic strokes among young women.

Adolescent↗
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↗
PubMed2004

FDG-PET is superior to gallium scintigraphy in staging and more sensitive in the follow-up of patients with de novo Hodgkin lymphoma: a blinded comparison.

Accurate staging of Hodgkin lymphoma (HD) allows for minimization of therapy and reduction of long-term toxicities. The present study prospectively compares FDG-PET with gallium/SPECT scintigraphy at time of diagnosis and in follow-up of 36 patients with HD. Prior to therapy, whole body FDG-PET and gallium/SPECT were performed. Follow-up scans were obtained after 3 cycles of chemotherapy (n = 22), and at the end of chemotherapy (n = 32). Two nuclear medicine physicians independently interpreted scans in blinded and random order and a consensus was obtained. Baseline scans revealed a greater number of supradiaphragmatic disease sites detected by PET, and 5 patients had splenic involvement on PET not noted by gallium (P = 0.05); 3 patients were upstaged on PET. Midway through therapy, 5 patients had positive PET (4 of whom relapsed), and 3 had positive gallium (1 relapsed). At conclusion of chemotherapy, 8 patients had a positive PET (4 relapsed) and 3 had a positive gallium (2 relapsed). In conclusion, diagnostic PET and gallium are largely concordant, with the exception of unique detection of splenic disease by PET. However, more patients have persistently positive PET at the end of chemotherapy compared with gallium (P = 0.04), although only half of these patients have relapsed.

Adolescent↗
PubMed2004

Autologous bone marrow transplantation for marginal zone non-Hodgkin's lymphoma.

The marginal zone non-Hodgkin's lymphomas are a recently defined group of related low-grade B cell malignancies whose natural history is heterogeneous. The optimal therapy is often unclear, particularly for the subset of patients with disseminated disease that behaves aggressively. We have retrospectively analyzed the outcomes of 11 patients with chemosensitive but disseminated marginal zone lymphomas who underwent uniform conditioning with cyclophosphamide and total body irradiation followed by bone marrow transplantation (BMT) with anti-B cell monoclonal antibody-purged autologous bone marrow between January 1994 and September 1999. All patients had stage IV disease and received multiple chemotherapy regimens prior to autologous BMT. Only 36% were in complete remission at the time of bone marrow harvest, and 36% had overt bone marrow infiltration at that time. Two treatment-related deaths occurred between 100 days and 6 months. Three patients relapsed and died of disease. One patient developed and died of myelodysplasia. Five patients remain in continuous complete remission at a median follow-up of 52 months (45%). The median progression-free survival for these patients was 56 months, with median overall survival 58 months. The only significant predictor of disease-free and overall survival was age at the time of transplant; no patient under 45 at the time of transplant has relapsed or died of any cause (P = 0.003). Outcomes of autologous BMT in patients with disseminated marginal zone NHL are similar to those in follicular NHL, and suggest that certain patients may experience prolonged disease-free survival.

Adult↗
PubMed2004

Chemoprevention by grape seed extract and genistein in carcinogen-induced mammary cancer in rats is diet dependent.

Many popular dietary supplements are enriched in polyphenols such as the soy isoflavones, tea catechins, and resveratrol (from grape skins), each of which has been shown to have chemopreventive activity in cellular models of cancer. The proanthocyanidins, which are oligomers of the catechins, are enriched in grape seeds and form the basis of the dietary supplement grape seed extract (GSE). Evidence suggests that the proanthocyanidins may be metabolized to the monomeric catechins. This study was carried out to determine whether GSE added to rodent diets protected against carcinogen-induced mammary tumorigenesis in rats and whether this was affected by the composition of the whole diet. Female rats were begun on 5%, 1.25%, or 0% (control) GSE-supplemented diets at age 35 d. At age 50 d they were administered 7,12-dimethylbenz[a]anthracene (DMBA) in sesame oil at 80 mg/kg body weight. They were weighed and monitored weekly for tumor development until 120 d after DMBA administration. Administration of GSE in AIN-76A diet did not show any protective activity of GSE against DMBA-induced breast cancer. However, administration of GSE in a laboratory dry food diet (Teklad 4% rodent diet) resulted in a 50% reduction in tumor multiplicity. In similar experiments, genistein administered in AIN-76A diet also failed to show chemopreventive activity against the carcinogen N-methyl-N-nitrosourea; however, when administered at the same dose in the Teklad 4% rodent diet, genistein exhibited significant chemopreventive activity (44-61%). These results demonstrate that GSE is chemopreventive in an animal model of breast cancer; moreover, the diet dependency of the chemopreventive activity for both GSE and genistein suggests that whether or not a compound is chemopreventive may depend on the diet in which the agent is administered.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2004

Effects of stapedectomy on tinnitus in patients with otosclerosis.

Tinnitus frequently accompanies hearing loss in patients with otosclerosis and has been correlated with distinct otosclerotic pathologies. The objective of our study was to evaluate the effect of stapedectomy on tinnitus in patients with otosclerosis. Forty patients were retrospectively interviewed for assessment of preoperative versus postoperative levels of tinnitus distress using the standardized Klockhoff-Lindblom (K/L) classification system. Audiometric data also were examined with respect to tinnitus grades. Of the 40 patients, 34 (85%) had improved K/L tinnitus grades after stapedectomy, 5 (12.5%) had no change, and 1 (2.5%) had a worse K/L grade postoperatively. Twenty-one (52.5%) patients reported complete resolution of tinnitus. Postoperative air-bone gap was less for patients with decreased tinnitus than for those with no change. Significant improvement was seen in the degree of tinnitus distress after stapedectomy for otosclerosis.

Adolescent↗
PubMed2003

Multiple genome-wide analyses of smoking behavior in the Framingham Heart Study.

BACKGROUND: Cigarette smoking behavior may have a genetic basis. We assessed evidence for quantitative trait loci (QTLs) affecting the maximum number of cigarettes smoked per day, a trait meant to quantify this behavior, using data collected over 40 years as part of the Framingham Heart Study's original and offspring cohorts. RESULTS: Heritability was estimated to be approximately 21% using variance components (VC) methods (SOLAR), while oligogenic linkage and segregation analysis based on Bayesian Markov chain Monte Carlo (MCMC) methods (LOKI) estimated a mean of two large QTLs contributing approximately 28% and 20%, respectively, to the trait's variance. Genome-wide parametric (FASTLINK) and VC linkage analyses (SOLAR) revealed several LOD scores greater than 1.0, with peak LOD scores using both methods on chromosomes 2, 17, and 20; multi-point MCMC methods followed up on these chromosomes. The most robust linkage results were for a QTL between 65 and 84 cM on chromosome 20 with signals from multiple sex- and age-adjusted analyses including two-point LOD scores of 1.30 (parametric) and 1.07 (heritability = 0.17, VC) at 70.51 cM, a multi-point LOD score of 1.50 (heritability = 0.20, VC) at 84 cM, and an intensity ratio of 12.0 (MCMC) at 65 cM. CONCLUSION: Familial aggregation of the maximum number of cigarettes smoked per day was consistent with a genetic component to this behavior, and oligogenic segregation analyses using MCMC suggested two important QTLs. Linkage signals on chromosome 20 between 65 and 84 cM were seen using multiple analytical methods. No linkage result, however, met genome-wide statistical significance criteria, and the true relationship between these regions and smoking behavior remains unclear.

Adolescent↗
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↗