Increased salivary syndecan-1 level is associated with salivary gland function and inflammation in patients with Sjögren's syndrome.

OBJECTIVE: Syndecan-1 (SDC-1), a transmembrane heparin sulphate proteoglycan predominantly expressed on epithelial cells, also exists in a soluble form through ectodomain shedding. SDC-1 expression and shedding may be modulated in the inflammatory milieu of primary Sjögren's syndrome (SS). We investigated SDC-1 expression in minor salivary glands (MSGs) and analysed the association between salivary or plasma levels of SDC-1 and clinical parameters in SS. METHOD: We measured salivary and plasma SDC-1 levels via an enzyme-linked immunosorbent assay and assessed the salivary flow rates (SFRs) in 70 patients with SS and 35 healthy subjects. Disease activity indices, serological markers, salivary gland scintigraphy, and MSG biopsy were evaluated in patients with SS. RESULTS: SDC-1 expression was upregulated on ductal epithelial cells in inflamed salivary glands. Salivary SDC-1 levels in patients significantly exceeded those in healthy subjects [median (interquartile range) 49.0 (20.7-79.1) vs 3.7 (1.7-6.3) ng/mL, p < 0.001] and inversely correlated with SFRs (r = -0.358, p = 0.032) and ejection fractions of the parotid (r = -0.363, p = 0.027) and submandibular (r = -0.485, p = 0.002) glands in salivary gland scintigraphy. Plasma SDC-1 levels were significantly correlated with the EULAR Sjögren's Syndrome Disease Activity Index (r = 0.507, p < 0.001) and EULAR Sjögren's Syndrome Patient Reported Index (r = 0.267, p = 0.033). Focus scores were correlated with salivary SDC-1 levels (r = 0.551, p = 0.004). CONCLUSIONS: Salivary and plasma SDC-1 levels may constitute potential biomarkers for salivary gland function and disease activity, respectively, in SS.

Incidence and Distribution of the Pathogens Causing Central Nervous System Infections at the University Hospital of Korea.

BACKGROUND: The pathogens involved in central nervous system (CNS) infections are various, such as viruses, bacteria, and fungi, so a syndromic approach can be required. In addition, since their rapid and accurate detection is very crucial, molecular diagnostics using cerebrospinal fluid is becoming the emerging standard method. METHODS: The study was conducted retrospectively to identify the incidence and distribution patterns of the pathogens according to gender, age, season, and month and to analyze their codetection from August 2017 to July 2020. It was also conducted to investigate turn-around times (TATs) according to the detection method. The detection methods were FilmArray® Meningitis/Encephalitis (M/E) method (FilmArray), Cepheid® Xpert EV assay (Xpert), and Multiplex PCR method for five species of bacteria. RESULTS: The overall incidence for at least one pathogen was 13.9% (346/2,496). The highest incidence was shown in age group 4 (3 - 6 years), with 27.4%. The detection rates by FilmArray, Xpert, and Multiplex PCR method were 39.8%, 41.7%, and 0.4%, respectively. Enterovirus (EV) showed the highest incidence rate, which accounted for 37.0%. The distribution of the pathogens according to the age groups were the highest in age group 4, with 47.5% (168/354), followed by 27.4% (97/354) in age group 5. Of the ten cases in which bacteria were detected, S. agalactiae accounted for 60.0% (6/10), most of which occurred in age group 1. E. coli K1, L. monocytogenes, and N. meningitidis were not detected. In the viral distribution, EV accounted for the highest proportion in all age groups. The overall proportion of EV accounted for 87.6% (310/354), followed by human parechovirus with 2.8% (10/354). The most commonly detected season was summer, comprising 75.1%. A total of eight cases of co-detection with two pathogens accounted for 1.6% (8/507) in FilmArray. In FilmArray, all TATs were found to be shorter than Xpert. CONCLUSIONS: The information on the incidence and distribution patterns of the pathogens causing CNS infections and their rapid detection are critically important to clinicians in the management of immunocompromised patients, elderly, and children. The expeditious molecular diagnostics for these pathogens would be valuable in medical decisions by clinicians.

Molecular Targets of the Hydrophobic Block of Pluronics in Cells: a Photo Affinity Labelling Approach.

PURPOSE: Pluronics are known as inhibitors of multidrug resistance thus making tumor cells sensitive to therapeutic doses of drugs. The purpose of our study consists in revealing molecular targets of the hydrophobic poly(propylene oxide) block of pluronics in living cells and the dependence of the polymers chemosensitizing efficiency upon targeting. METHODS: A photo sensitive tracer was attached to the hydrophobic poly(propylene oxide) block of 3H-labeled tert-Bu-EO-PO copolymer. The conjugate was used for treatment cells in culture. We searched for its complexes with cellular lipids or proteins using RP TLC and SDS-electrophoresis, respectively. The chemosensitizing efficiency of pluronics was evaluated by their least concentrations sufficient for MDR reversion (CMDR). RESULTS: The poly(propylene oxide) block inserts in the lipid core of plasma membrane. No preferential binding of the conjugate with any cellular protein, particularly P-gp, has been detected. FITC-labeled pluronic L61 bound to alcohol insoluble cellular targets did not participate in MDR reversion. CMDR values of 13 block copolymers have been determined. These values inversely correlated with the polymers affinity toward lipids and the ability to accelerate flip-flop. CONCLUSION: Insertion of the hydrophobic poly(propylene oxide) block of amphiphiles in the lipid core of plasma membrane and acceleration of flip-flop of lipids underlie the mechanism of MDR reversion.

Eupatilin Alleviates Hyperlipidemia in Mice by Inhibiting HMG-CoA Reductase.

Artemisia princeps (family Asteraceae) is a natural product broadly used as an antioxidative, hepatoprotective, antibacterial, and anti-inflammatory agent in East Asia. In the present study, eupatilin, the main constituent of Artemisia princeps, was investigated as an antihyperlipidemic agent. Eupatilin inhibited 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HCR), an enzyme that is a therapeutic target for hyperlipidemia, in an ex vivo assay using rat liver. In addition, oral administration of eupatilin significantly lowered the serum levels of total cholesterol (TC) and triglycerides (TG) in corn oil-induced and Triton WR-1339-induced hyperlipidemic mice. These results suggest that eupatilin can alleviate hyperlipidemia by inhibiting HCR.

CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid arthritis.

The chemokine receptor [C-C chemokine receptor 5 (CCR5)] is expressed on diverse immune effecter cells and has been implicated in the pathogenesis of rheumatoid arthritis (RA). This study sought to determine whether single-nucleotide polymorphisms (SNPs) in the CCR5 gene and their haplotypes were associated with susceptibility to and severity of RA. Three hundred fifty-seven patients with RA and 383 healthy unrelated controls were recruited. Using a pyrosequencing assay, we examined four polymorphisms -1118 CTAT(ins) (/del) (rs10577983), 303 A>G (rs1799987), 927 C>T (rs1800024), and 4838 G>T (rs1800874) of the CCR5 gene, which were distributed over the promoter region as well as the 5' and 3' untranslated regions. No significant difference in the genotype, allele, and haplotype frequencies of the four selected SNPs was observed between RA patients and controls. CCR5 polymorphisms of -1118 CTAT(del) (P = 0.012; corrected P = 0.048) and 303 A>G (P = 0.012; corrected P = 0.048) showed a significant association with radiographic severity in a recessive model, and, as a result of multivariate logistic regression analysis, were found to be an independent predictor of radiographic severity. When we separated the erosion score from the total Sharp score, the statistical significance of CCR5 polymorphisms showed an increase; -1118 CTAT(ins) (/del) (P = 0.007; corrected P = 0.028) and 303 A>G (P = 0.007; corrected P = 0.028). Neither SNPs nor haplotypes of the CCR5 gene showed a significant association with joint space narrowing score. These results indicate that genetic polymorphisms of CCR5 are an independent risk factor for radiographic severity denoted by modified Sharp score, particularly joint erosion in RA.

Insular cortex is a trait marker for pain processing in fibromyalgia syndrome--blood oxygenation level-dependent functional magnetic resonance imaging study in Korea.

OBJECTIVES: To investigate the variability in cerebral activation according to pain intensity and the association between variability in cerebral activation and clinical features in patients with fibromyalgia syndrome (FMS) using functional magnetic resonance imaging (fMRI). METHODS: Nineteen FMS female patients and 22 age-matched healthy female controls were enrolled in this study. Changes in cerebral activation area were measured using blood oxygenation level-dependent (BOLD) contrast fMRI after application of both medium and high pressure stimuli to the left thumbnail bed. RESULTS: We identified the insular cortex (IC) and superior temporal gyrus (STG) as regions of interest (ROIs) in this analysis. Cerebral activation at the bilateral IC in response to high pressure stimuli was significantly greater in FMS patients than it was in the controls, whereas there were no differences in BOLD signal changes in the STG regions between FMS patients and controls, irrespective of pain level. Prominent signal changes at both ROIs in FMS patients were noted between high and medium pressure (p<0.001 contralateral IC, p=0.001 for ipsilateral IC, p=0.008 for contralateral STG, and p=0.049 for ipsilateral STG). BOLD signal changes on the contralateral STG after medium stimuli were correlated with tender point count (r=0.586, p=0.013). CONCLUSIONS: This study revealed more distinct signal variability in the ICs in FMS patients than in those of controls in response to high pressure stimuli. The IC can therefore be considered to be a region susceptible to pain perception in FMS patients.

Phosphatidylserine-Gold Nanoparticles (PS-AuNP) Induce Prostate and Breast Cancer Cell Apoptosis.

Prostate and breast cancer are the current leading causes of new cancer cases in males and females, respectively. Phosphatidylserine (PS) is an essential lipid that mediates macrophage efferocytosis and is dysregulated in tumors. Therefore, developing therapies that selectively restore PS may be a potential therapeutic approach for carcinogenesis. Among the nanomedicine strategies for delivering PS, biocompatible gold nanoparticles (AuNPs) have an extensive track record in biomedical applications. In this study, we synthesized biomimetic phosphatidylserine-caped gold nanoparticles (PS-AuNPs) and tested their anticancer potential in breast and prostate cancer cells in vitro. We found that both cell lines exhibited changes in cell morphology indicative of apoptosis. After evaluating for histone-associated DNA fragments, a hallmark of apoptosis, we found significant increases in DNA fragmentation upon PS-AuNP treatment compared to the control treatment. These findings demonstrate the use of phosphatidylserine coupled with gold nanoparticles as a potential treatment for prostate and breast cancer. To the best of our knowledge, this is the first time that a phosphatidylserine-capped AuNP has been examined for its therapeutic potential in cancer therapy.

Functional variability of the adenosine A3 receptor (ADORA3) gene polymorphism in aspirin-induced urticaria.

BACKGROUND: To improve understanding of aspirin hypersensitivity, this study focused on adenosine as a noncyclooxygenase target molecule of aspirin. Adenosine may affect the release of histamine from cutaneous mast cells through a mechanism mediated by the adenosine A3 receptor. OBJECTIVES: To investigate the genetic contribution of adenosine A3 receptor gene (ADORA3) polymorphisms in the pathogenesis of aspirin-induced urticaria (AIU) in a case-control association study in a Korean population. METHODS: A case-control association study was performed in 385 patients with AIU and 213 normal controls from a Korean population. The functional variability of genetic polymorphisms in the ADORA3 gene was analysed in in vitro studies that included a luciferase reporter assay and an electrophoretic mobility shift assay (EMSA), and ex vivo studies that included real-time polymerase chain reaction for mRNA expression in peripheral blood mononuclear cells and a histamine release assay. RESULTS: A significant association of ADORA3 promoter polymorphism at -1050G/T was found with the phenotype of AIU. Patients with AIU showed higher frequency of the haplotype, ht1 (T(-1050) C(-564) ), compared with normal healthy controls. Moreover, ht1 (TC) was found to be a high-transcript haplotype by the luciferase activity assay, and a -564C allele-specific DNA binding protein was found by EMSA. Increased basophil histamine release was noted in subjects who had the high-transcript haplotype, ht1 (TC). CONCLUSION: These results suggest that the high-transcript haplotype, ht1 (TC), of the ADORA3 gene may contribute to the development of cutaneous hyper-reactivity to aspirin, leading to the clinical presentation of AIU.

Beta-glycosidase of Thermus thermophilus KNOUC202: gene and biochemical properties of the enzyme expressed in Escherichia coli.

The beta-glycosidase gene of Thermus thermophilus KNOUC202 was cloned, expressed in Escherichia coli JM109(DE3), and the enzyme was purified and characterized. The gene (KNOUC202/beta-gly) was composed of 1296 bp encoding a beta-glycosidase (KNOUC202beta-glycosidase) of 431 a.a., belonging to the family 1 of glycosyl hydrolase. The gene was expressed as monomer of 430 a.a. with amino terminal methionine excised in E. coli JM109(DE3). The enzyme hydrolyzed beta-glycosides whose glycone are galactose, glucose and fucose well, however showed no or very low activity on beta-D-glycosides whose glycone are disaccharides and xylose. kcat of the enzyme for the hydrolysis of p-Nph-beta-D-Glcp was lower than those for p-Nph-beta-D-Galp and ONPG, however K(m) for p-Nph-beta-D-Glcp was highly lower than those for p-Nph-beta-D-Galp and ONPG resulting in the catalytic efficiency(k(cat)/K(m)) for the hydrolysis of p-Nph-beta-D-Glcp much higher than those for p-Nph-beta-D-Galp and ONPG. Optimum pH and optimum temperature of the enzyme were pH 5.4 and 90 degrees C. The enzyme has high thermostability, not losing its activity at 80 degrees C for 2 h in 0.05 M Na-phosphate buffer of pH 6.8 with T(m) of 100.0 +/- 0.031 degrees C in 0.02 M Tris-HCl buffer of pH 8.2. The beta-glycosidase produced a disaccharide composed of galactose as transglycosylation byproduct during hydrolysis of lactose.

The effects of body mass index and body shape perceptions of South Korean adults on weight control behaviors; Correlation with quality of sleep and residence of place.

BACKGROUND/OBJECTIVES: The obese population is rapidly increasing because of reduced physical activity and a Westernized diet; consequently, various chronic diseases are more prevalent. With the increasing interest in body shape and appearance, research on body shape perceptions and accompanying weight control behaviors are needed for healthy weight management. SUBJECTS/METHODS: A cross-sectional survey was conducted on randomly selected 536 (209 men and 327 women) aged 20 to 65 years. Body mass index (BMI), body-shape perception, weight control behavior, quality of sleep, and place of residence were collected using self-reported questionnaires. Multivariable logistic regression analysis was conducted using complex design in each groups. Collected data were analyzed using the SAS 9.4 statistical package, and the significance level was set at P < 0.05. RESULTS: When these two variables were divided into four groups, they were found to influence dieting attempts. People with abnormal weights who were dissatisfied with their body shapes attempted dieting 5.23 times more than those with healthy weights and satisfaction with their body shapes. Further, those with normal weights but dissatisfaction with their bodies attempted dieting 4.45 times more than those who were satisfied with their shapes. Subjects in their 20s attempted dieting 2.53 times more than those in their 30s and 40s, and female subjects attempted dieting 2.24 times more than male subjects. CONCLUSIONS: A correct perception of one's shape can be an important factor for dietary behavior, as body shape perceptions and dieting attempts are strongly related. Additionally, healthy weight management and nutrition education are important elements to incorporate into a weight control program aimed at preventing excessive weight control behaviors and promoting correct perceptions of body shape.

Combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis.

OBJECTIVE: To determine the efficacy and safety of the combination of leflunomide and methotrexate for the treatment of patients with active rheumatoid arthritis (RA) in an open, non-comparative, multicentre trial. METHODS: Seventy-four patients with active RA were enrolled to receive concomitantly leflunomide (no loading dose, 10 mg/day) and methotrexate (starting at 7.5 mg/week and titrating up to 15 mg/week) for 20 weeks. The primary end-point was a 20% improvement in the American College of Rheumatology (ACR) criteria at 20 weeks. Safety measures included evaluation of adverse events at each visit and laboratory data, including haematology and liver function tests. Intention-to-treat analyses were conducted. RESULTS: Sixty-five patients completed 20 weeks of treatment, and 71.6% were responders based on the ACR20 criteria. After 20 weeks, the mean changes were -16.3 for tender joint count, -12.0 for swollen joint count, -44.0 for physician global assessment, -34.3 for patient global assessment, -22.7 for erythrocyte sedimentation rate, and -0.65 for the Health Assessment Questionnaire score. Adverse events occurred in 40.5% of the patients, and were considered serious in four patients who discontinued therapy. Abnormal liver function was noted for 16 patients (21.6%). Two of these patients were withdrawn from the study; after discontinuing the medication, their liver function recovered fully. CONCLUSION: THE combination of leflunomide and methotrexate was effective and well tolerated in the treatment of active RA patients. This combination may be a useful option as an initial treatment for active RA before starting biological agents.

Assessing cancer treatment related information online: unintended retrieval of complementary and alternative medicine web sites.

The aims of this study were to determine the number of Complementary and Alternative Medicine (CAM) web sites retrieved form Korean search engines, and to evaluate the quality of online CAM content. We evaluated results retrieved by the use of the key word 'anticancer treatment' on six common search engines in Korea. Among a total of 651 web sites, 226 web sites (35%) related to CAM were identified. The quality and risk of these sites were assessed for 97 web sites after removing duplicate and dysfunctional web sites. We evaluated the quality of the sites using Sandvik score. Scores in this study varied between 5 and 12 points, with a maximum of 14 points. We categorized the risk score for each web site based on the following criteria: (1) the site discourages the use of conventional medicine (23%: 22/97); (2) the site discourages adherence to the advice of a clinician (15%:15/97); (3) the site either provides opinions and experiences, or factual details (26%: 25/97); and (4) the site provides commercial details (46%: 45/97). The most popular web sites in Korea that relate to CAM for cancer offer information of extremely variable quality. Clinicians should be aware of the risks of inaccurate online information and attempt to protect their patients from those.

Randomized phase II study of irinotecan, leucovorin and 5-fluorouracil (ILF) versus cisplatin plus ILF (PILF) combination chemotherapy for advanced gastric cancer.

BACKGROUND: Irinotecan, in combination with 5-fluorouracil (5-FU) or cisplatin, has demonstrated efficacy against advanced gastric cancer (AGC). PATIENTS AND METHODS: Chemotherapy-naive AGC patients were randomly assigned to receive irinotecan 150 mg/m(2) on day 1, leucovorin 20 mg/m(2) and a 22-h infusion of 5-FU 1000 mg/m(2) on days 1 and 2 (ILF) or ILF plus cisplatin 30 mg/m(2) on day 2 (PILF). Treatment was repeated every 2 weeks. RESULTS: Of 91 registered patients, 45 patients were treated with ILF and 45 with PILF. For both arms, 687 chemotherapy cycles were delivered (median = 7 for ILF and 8 for PILF). Both ILF and PILF were generally well tolerated and there was no relevant difference in the occurrence of overall grade 3/4 toxic effects between the two arms. Four patients died during treatment: one in the ILF and three in the PILF arm. The objective response rate was 42% for both arms. There was no significant difference in therapeutic efficacy between ILF and PILF with respect to progression-free survival (4.8 versus 6.2 months; P = 0.523) and overall survival (10.7 versus 10.5 months; P = 0.850). CONCLUSION: Both ILF and PILF are active as first-line chemotherapy for AGC. The addition of cisplatin, however, has no clear advantage over ILF.

Accuracy of perfusion-CT in predicting malignant middle cerebral artery brain infarction.

BACKGROUND: We performed a prospective study on patients with middle cerebral artery(MCA) ischemic stroke to evaluate the accuracy of perfusion-CT imaging(PCT) to predict the development of malignant brain infarction (MBI). METHODS: 106 patients(women 37 %, mean age 65 years)underwent native cranial computed tomography (CCT), CT angiography(CTA) and PCT after a median of 2 h after stroke onset. We assessed the patency of the MCA and the area of tissue ischemia (AIT)according to cerebral blood flow(CBF), cerebral blood volume (CBV) and time-to-peak (TTP)maps. Optimum sensitivity, specificity,positive (PPV) and negative predictive values (NPV) were calculated for the end-point MBI (= midline shift > 5 mm or decompressive surgery) by means of receiver operating characteristics(ROC). RESULTS: 20 patients (19 %)developed a MBI. In these patients,a larger AIT was found in all perfusion maps as compared to the remaining patients (p < 0.001). All perfusion maps had a very high NPV (95.4-98.4 %), a high sensitivity (85-95 %) and specificity (71.6-77.9 %) and only a moderate PPV (44-47.4 %). Best prediction was found for CBF maps with AIT of > 27.9 % of the hemisphere. CONCLUSION: PCT allows the discrimination of patients without a relevant risk for MBI from those having a 50 % risk of MBI development. Due to the high sensitivity and specificity, PCT is a reliable tool in detecting MBI. Because of PCT's better availability, it is the method of choice at present for an early risk stratification of acute stroke patients.

[6]-Gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells.

Gingerol (Zingiber officinale Roscoe, Zingiberaceae) is one of the most frequently and heavily consumed dietary condiments throughout the world. The oleoresin from rhizomes of ginger contains [6]-gingerol (1-[4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone) and its homologs which are pungent ingredients that have been found to possess many interesting pharmacological and physiological activities, such as anti-inflammatory, antihepatotoxic and cardiotonic effects. However, the effects of [6]-gingerol on metastatic processes in breast cancer cells are not currently well known. Therefore, in this study, we examined the effects of [6]-gingerol on adhesion, invasion, motility, activity and the amount of MMP-2 or -9 in the MDA-MB-231 human breast cancer cell line. We cultured MDA-MB-231 cells in the presence of various concentrations of [6]-gingerol (0, 2.5, 5 and 10 microM). [6]-Gingerol had no effect on cell adhesion up to 5 microM, but resulted in a 16% reduction at 10 microM. Treatment of MDA-MB-231 cells with increasing concentrations of [6]-gingerol led to a concentration-dependent decrease in cell migration and motility. The activities of MMP-2 or MMP-9 in MDA-MB-231 cells were decreased by treatment with [6]-gingerol and occurred in a dose-dependent manner. The amount of MMP-2 protein was decreased in a dose-dependent manner, although there was no change in the MMP-9 protein levels following treatment with [6]-gingerol. MMP-2 and MMP-9 mRNA expression were decreased by [6]-gingerol treatment. In conclusion, we have shown that [6]-gingerol inhibits cell adhesion, invasion, motility and activities of MMP-2 and MMP-9 in MDA-MB-231 human breast cancer cell lines.

Alteration of cell-cycle regulation in epithelial ovarian cancer.

In spite of the clinical importance of epithelial ovarian cancer (EOC), little is known about the pathobiology of its precursor lesions and progression. Regulatory mechanisms of the cell cycle are mainly composed of cyclins, cyclin-dependent kinases (CDK), and CDK inhibitors. Alteration of these mechanisms results in uncontrolled cell proliferation, which is a distinctive feature of human cancers. This review describes the current state of knowledge about the alterations of cell-cycle regulations in the context of p16-cyclin D1-CDK4/6-pRb pathway, p21-p27-cyclin E-CDK2 pathway, p14-MDM2-p53 pathway, and ATM-Chk2-CDC25 pathway, respectively. Recent evidence suggests that ovarian cancer is a heterogenous group of neoplasms with several different histologic types, each with its own underlying molecular genetic mechanism. Therefore, expression of cell cycle regulatory proteins should be tested separately according to each histologic type. In serous ovarian carcinoma, high expression of p16, p53, and p27 and low expression of p21 and cyclin E were shown. In addition, this review focuses on the prognostic significance of cell cycle-regulating proteins in EOC. However, it is difficult to compare the results from different groups due to diverse methodologies and interpretations. Accordingly, researchers should establish standardized criteria for the interpretation of immunohistochemical results.

Methyl-donor nutrients inhibit breast cancer cell growth.

Lipotropes (methyl group containing nutrients, including methionine, choline, folate, and vitamin B(12)) are dietary methyl donors and cofactors that are involved in one-carbon metabolism, which is important for genomic DNA methylation reactions and nucleic acid synthesis. One-carbon metabolism provides methyl groups for all biological methylation pathways and is highly dependent on dietary supplementation of methyl nutrients. Nutrition is an important determinant of breast cancer risk and tumor behavior, and dietary intervention may be an effective approach to prevent breast cancer. Apoptosis is important for the regulation of homeostasis and tumorigenesis. The anti-apoptotic protein Bcl-2 may be a regulatory target in cancer therapy; controlling or modulating its expression may be a therapeutic strategy against breast cancer. In this study, the effects of lipotrope supplementation on the growth and death of human breast cancer cell lines T47D and MCF-7 were examined and found to inhibit growth of both T47D and MCF-7 cells. Furthermore, the ratios of apoptotic cells to the total number of cells were approximately 44% and 34% higher in the lipotrope-supplemented treatments of T47D and MCF-7 cancer cells, respectively, compared with the control treatments. More importantly, Bcl-2 protein expression was decreased by approximately 25% from lipotrope supplementation in T47D cells, suggesting that lipotropes can induce breast cancer cell death by direct downregulation of Bcl-2 protein expression. Cancer treatment failure is often correlated with Bcl-2 protein upregulation. These data may be useful in the development of effective nutritional strategies to prevent and reduce breast cancer in humans.

Effects of hypoxia-inducible factor-1alpha expression and C4d deposition in implantation biopsies on renal allograft.

Upregulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in response to ischemic states has been suggested to have a role in the development of chronic allograft nephropathy. Deposition of C4d in the peritubular capillaries of renal allografts has been reported to be a sensitive marker of acute humoral rejection. The purpose of this study was to determine the effects of HIF-1alpha expression and C4d deposition in implantation biopsies of renal allografts. Implantation biopsies and 22 rejection proved biopsies were performed in 54 renal transplant recipients between December 1996 and July 1999. The mean follow-up was 82.8 months. Immunohistochemical studies were performed using a mouse monoclonal antibody for HIF-1alpha expression and a rabbit polyclonal antibody for C4d detection. HIF-1alpha was demonstrated in 19 of 54 implantation biopsies (35%), and C4d deposition in one (1.9%). The HIF-1alpha-positive group included a higher percentage of deceased donor organs (66.4% vs 17.1%; P = .002) and longer mean cold ischemia times (261.3 +/- 231 vs 103 +/- 40 min; P = .008) compared with the HIF-1alpha-negative group. The relative risks (95% confidence intervals) of expression of HIF-1alpha for allograft rejection, chronic allograft nephropathy, and graft loss were 1.53 (0.82-2.87), 0.61 (0.06-5.50), and 2.45 (0.62-9.85). The C4d-positive patient developed acute accelerated rejection on postoperative day 4. In the present study, the expression of HIF-1alpha showed a significant correlation with the use of a deceased donor kidney and with cold ischemia time. However, there were no significant effects on the prognosis for a graft after implantation of a kidney with HIF-1alpha expression.