Clinical relevance of lymph node ratio in breast cancer patients with one to three positive lymph nodes.

BACKGROUND: To test the hypotheses that breast cancer patients with one to three positive lymph nodes (pN1) consist of heterogeneous prognostic subsets and that the ratio of positive nodes to total nodes dissected (lymph node ratio, LNR) might discriminate patients with a higher risk as candidates for post-mastectomy radiation therapy (PMRT). METHODS: Using information from 7741 node-positive patients, we first identified cutoff values of the LNR using the nonparametric bootstrap method. Focusing on 3477 patients with pN1 disease, we then evaluated the clinical relevance of the LNR categorised by the estimated cutoff values (categorised LNR, cLNR). RESULTS: Among 3477 patients with pN1 disease, 3059 and 418 patients were assigned into the low and intermediate cLNR groups, respectively, based on a cutoff value of 0.18. The prognostic factors associated with poor overall survival (OS) included younger age, T2 stage, negative oestrogen/progesterone receptors, high histologic grade, and intermediate cLNR. Post-mastectomy radiation therapy significantly increased OS in patients assigned to the intermediate cLNR (hazard ratio, 0.39; 95% confidence interval, 0.17-0.89; P=0.0248), whereas patients in the low cLNR group derived no additional survival benefit from PMRT. CONCLUSION: This study suggests that PMRT should be recommended for patients with pN1 disease and an intermediate cLNR.

Prognosis of papillary thyroid carcinoma in relation to preoperative subclinical hypothyroidism.

INTRODUCTION: It has been established that thyroid-stimulating hormone (TSH) stimulates the growth and development of thyroid malignancy, and a higher serum TSH level is associated with the incidence of thyroid cancer and an advanced tumour stage. This study aimed to evaluate the association of preoperative subclinical hypothyroidism with the prognosis of papillary thyroid cancer (PTC). METHODS: A total of 466 patients who underwent surgery for PTC between December 2006 and June 2009 were enrolled. Among them, 44 patients had subclinical hypothyroidism, while 422 did not have subclinical hypothyroidism, as diagnosed using the preoperative thyroid function test. We compared the recurrence rate and association with clinicopathological features in the two groups. RESULTS: The median patient age was 46.9 years (17-74 years). There were 420 female and 46 male patients. The median follow-up duration was 81.4 months. There were no statistical differences between the two groups with respect to age, sex, tumour size, extrathyroidal extension, multifocality, lymph node metastasis, TNM stages, recurrence and disease-free survival, despite a significant difference in the average TSH concentrations of the two groups. CONCLUSIONS: Our results suggest that preoperative subclinical hypothyroidism was not associated with tumour aggressiveness and recurrence in PTC.

Cordycepin inhibits IL-1beta-induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts.

OBJECTIVE: MMP is a key enzyme in the degradation of extracellular matrices, and its expression plays important roles in inflammatory diseases. Cordycepin (3'-deoxyadenosine), a bioactive compound of Cordyceps militaris, has been shown to exhibit many pharmacological activities, such as anti-cancer, anti-inflammatory and anti-infection activities. In this study, we aimed at the inhibitory effect of cordycepin on IL-1beta-induced MMP-1 and MMP-3 expression as well as the molecular basis using RA synovial fibroblasts (RASFs). METHODS: RASFs were isolated from synovial tissue obtained from 12 patients with RA and cultured in monolayer. Expression of MMP-1 and MMP-3 was evaluated using western blotting and real-time PCR. Chemokines were analysed by ELISA. The phosphorylation of mitogen-activated protein kinase was measured by western blotting. Electrophoretic mobility shift assay was performed to evaluate binding activities of DNA to nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). RESULTS: Cordycepin inhibited IL-1beta-induced MMP-1 and MMP-3 expressions in RASFs in a dose-dependent manner. Among various chemokines [such as monocyte chemoattractant protein-1 (MCP-1), GRO-alpha, regulated upon activation, normal T-cell expressed and presumably secreted (RANTES) and epithelial neutrophil activating peptide 78 (ENA-78)], cordycepin specifically blocked IL-1beta-induced ENA-78 production in RASF. Moreover, cordycepin significantly inhibited IL-1beta-induced p38/JNK and AP-1 activation, but not extracellular signal-regulated kinase (ERK) and NF-kappaB activation. CONCLUSIONS: Cordycepin is a potent inhibitor of IL-1beta-induced chemokine production and MMP expression and strongly blocks the p38/JNK/AP-1 signalling pathway in RASFs.

Up-regulation of the expression of major histocompatibility complex class I antigens by plasmid DNA transfection in non-hematopoietic cells.

The effect of DNA on the surface expression of major histocompatibility (MHC) class I antigens was examined in non-hematopoietic tumor cell lines. Transfection with plasmid DNA via liposome or electroporation significantly increased the surface expression of MHC class I molecules in a transient manner. Northern blot analysis showed that levels of MHC class I mRNA were increased by DNA transfection, probably via transcriptional activation. In contrast, the expression of the MHC class II and beta-actin genes was not affected, suggesting that the up-regulation of MHC class I expression by plasmid DNA works in a gene-specific manner.

Osteoconduction at porous hydroxyapatite with various pore configurations.

To assess the histological response and the reinforcing effects of bone ingrowth within porous hydroxyapatite (HA) implants depending on pore geometry, four kinds of cylindrical-type with parallel linear pores phi50, 100, 300, 500 microm), one kind of sponge-type with irregular interconnecting pores (phi250 microm) and one cross-type with crossing linear pores (phi100 x 120 microm) of porous HA were prepared. Eighty-four rabbits were divided into six groups, and a 5 x 5 x 7 mm sized porous HA block was inserted through the medial cortical window of the proximal tibia. Histomorphological changes were examined using light and scanning electron microscopy. A biomechanical compression test was performed using material test machines. After implantation, the implants showed different histological changes depending on pore geometry. Active osteoconduction was also found in the phi50 microm sized cylindrical-type porous HA. Evidence of remodeling of new bone and bone marrow formation within porous HA was found in the larger cylindrical-types (phi300, 500 microm), and the sponge- and cross-types. The biomechanical test showed that the ultimate compressive strength increased significantly in the phi300 microm sized cylindrical-type, and in the sponge- and cross-types eight weeks after implantation. Porous HA with cylindrical pores could be a useful graft material due to its strength, osteoconductivity and the ease with which its pore geometry can be controlled.

Identification, expression, and nuclear location of murine Mage-b2 protein, a tumor-associated antigen.

MAGE-1, which was originally identified by reacting with cytolytic T lymphocytes derived from the blood of melanoma patients, is a member of a gene family consisting of 17 structurally related genes. The MAGE genes are expressed only in the testis among normal tissues and in a number of human tumors of various histological types. Murine MAGE (also called SMAGE or Mage) genes were found in a study aimed at detecting mouse genes homologous to human MAGE genes. However, the biological functions of MAGE and Mage are currently unknown. To understand the biological functions of Mage, in the present study a recombinant SMAGE2 (Mage-b2) protein of 43 kDa was produced and monoclonal antibodies reactive with Mage-b2 protein were generated. One monoclonal antibody, smpG4A, specifically recognized a 43 kDa protein in lysates of Mage-b2 mRNA-positive sarcoma cells and of the testis. Immunohistochemistry showed that Mage-b2 is located in the nucleus of Mage-b2 mRNA-positive sarcoma cells. These results should contribute to understanding the biological functions of Mage.

Demonstration of penetrating intramyocardial coronary arteries with high-frequency transthoracic echocardiography and Doppler in human subjects.

Characterization of intramyocardial coronary artery flow may offer insight into the spectrum of coronary physiology. The purposes of this study were to test the feasibility of detection and measurement of intramyocardial coronary artery flow by using high-frequency transthoracic ultrasound and to evaluate the hemodynamic and morphologic differences in intramyocardial coronary arteries between patients with echocardiographically normal myocardium and patients with diseased myocardium. In 116 subjects (age 58 +/- 19 years; male:female 67:49; 58 normal [control subjects], 40 with left ventricular hypertrophy [LVH], 18 with systolic left ventricular dysfunction [cardiomyopathy, CM]), we examined the myocardium just beneath the apical impulse window at a depth of 3 to 5 cm by using a 6- or 7-MHz centerline frequency transducer. For color Doppler examination, a special preset coronary program with a low Nyquist limit (12 to 20 cm) was used. After obtaining linear color signals, the width and length, peak and mean diastolic pulsed Doppler flow velocities, diastolic velocity time integrals, and percent duration of diastolic Doppler flow were measured. The number of linear color flow signals per square centimeter was counted in 520 different cardiac cycles, and the angles formed by their inner curvature was measured with a graduated protractor. We identified color flow Doppler signals within the myocardium having a mean width of 1.1 +/- 0.4 mm and flow direction from epicardium to endocardium in 104 (89. 7%) subjects and spectral Doppler signals in 74 (63.8%) subjects. In 33 (45.8%) subjects, only diastolic flow was detected and in 39 (54. 2%) subjects, diastolic flow was predominant with systolic reversal. Peak and mean diastolic flow velocities and velocity time integrals of spectral Doppler signal in control subjects were 26.2 +/- 8.6 cm/s, 19.0 +/- 6.3 cm/s, and 9.5 +/- 2.7 cm, respectively. There were no significant differences in width and density of linear color flow signals among the 3 groups. The color flow signals in the LVH and CM groups had a narrower angle of inner curvature (P <.005 for LVH, P <.05 for CM, respectively), and their spectral Doppler signals showed significantly higher diastolic velocities and shorter diastolic flow duration (P <.005 for LVH, P <.05 for CM, respectively) than those of the control subjects. Detection and measurement of flow signals consistent with penetrating intramyocardial coronary arteries are feasible in a high percentage of subjects by use of high-frequency transthoracic ultrasound. The findings in patients with LVH and CM suggest that there are distinct hemodynamic and morphologic departures from those with normal left ventricles that may be a consequence of disordered myocardial perfusion in diseased myocardium.

Two-dimensional echocardiography with a 15-MHz transducer is a promising alternative for in vivo measurement of left ventricular mass in mice.

Murine models of left ventricular (LV) hypertrophy recently have been developed. We tested the accuracy of 2-dimensional (2D) echocardiographic measurement of LV mass with high-frequency imaging in mice. Ten anesthetized mice (weight 20 to 31 g, aged 1 to 5 months) were examined with a 15-MHz transthoracic linear-array transducer. End-diastolic myocardial area (A)(epicardial - endocardial) from the parasternal short-axis view at the midpapillary level and LV length (L) from the parasternal long-axis view were measured to calculate LV mass with the area-length method (1.05 [5/6 x A x L]) and data were compared with LV-mass with the 2D guided M-mode method. Within 3 days of echocardiography, the hearts were removed and weighed after potassium-induced cardiac arrest. Two-dimensional echocardiographic measurement with a 15-MHz transducer was performed in all mice. LV chamber dimensions included end-diastolic septal (0.80 +/- 0.12 mm) and posterior wall thickness (0.76 +/- 0.13 mm), end-diastolic dimension (3.64 +/- 0.28 mm), and end-systolic dimension (2.34 +/- 0.32 mm). Echocardiographic LV mass with the area-length method, 2D guided M-mode method, and autopsy LV weight were 80.8 +/- 16.1 mg, 97.6 +/- 17.8 mg, and 78.8 +/- 13.2 mg, respectively. A strong correlation existed between LV weight (x ) and echocardiographic LV mass (y ) with the area-length method: y = 0.745x + 18.9, r =0.908, standard error of estimate (SEE) = 5.9 mg, P <.0005. This correlation was stronger than that of LV weight (x ) and echocardiographic LV mass (y ) with the 2D guided M-mode method: y = 0.577x + 22.6, r =0.779, SEE = 8.8 mg, P =.008. These data suggest that serial in vivo measurements of LV mass with the 2D area-length method may be more accurate than M-mode methods in experimental murine models of LV pathology.

Transthoracic echocardiographic demonstration of massive pulmonary thrombus caused by protein C deficiency.

Few cases of pulmonary embolism detected by transthoracic echocardiography (TTE) have been reported. We present a case of a patient affected by pulmonary embolism caused by protein C deficiency. Transthoracic echocardiography showed a thrombus in transit (ie, visualization of a thrombus within the pulmonary artery). A hypercoagulable state caused by deficiency of protein C is a rare cause of pulmonary thromboembolism. Our experience demonstrates a massive pulmonary thrombus resulting from such a deficiency. Transthoracic echocardiography should be considered as the first diagnostic method for patients with suspected pulmonary embolism.

Transesophageal echocardiography (TEE) in the evaluation of the coronary arteries.

With technical advancements, including high frequency, multiplane transducers, digital acquisition and display, and left-sided contrast agents, TEE is emerging as a promising method for evaluating coronary artery disease. Visualization of proximal coronary artery stenoses and coronary artery anomalies is already possible. Research studies using TEE measurement have contributed to understanding coronary artery physiology and may prove to be a valuable clinical tool in the future.

Power motion imaging can improve image quality in stress conditions with tachycardia.

BACKGROUND: Stress echocardiographic studies are useful, but the evaluation of wall motion is sometimes suboptimal. The recently developed technique of power motion imaging can enhance mobile tissue definition. HYPOTHESIS: The study was undertaken to determine whether power motion imaging improves endocardial definition during tachycardia compared with conventional two-dimensional (2-D) imaging. METHODS: Twenty pigs were studied during pacing rates of 100, 120, and 150 beats/min. We compared power motion imaging with standard 2-D imaging using systolic thickening visualization (STV) scores (3 = excellent definition of systolic thickening approximately 0 = total lack of visualization of systolic thickening) at each heart rate. We calculated the sum of the scores of 22 left ventricular segments as the overall STV score, and also calculated the sum of the scores in 10 parasternal segments and 12 apical segments separately. RESULTS: The overall STV scores in both imaging methods were similar at 100 beats/min, but scores for power motion imaging were significantly higher than those of usual 2-D imaging at 120 and 150 beats/min. Using power motion imaging, the overall STV scores were similar as heart rate was increased; however, while using standard 2-D imaging, STV scores were significantly decreased as heart rate was increased. Findings were analyzed separately by parasternal and apical images. Especially in the parasternal images, the scores were significantly increased as heart rate was increased using power motion imaging. CONCLUSIONS: We conclude that power motion imaging improves the detection of endocardial border in stress condition with tachycardia, and thus this modality is useful for stress echocardiography.

Screening of the anticoccidial effects of herb extracts against Eimeria tenella.

Ionophorous antibiotics have been popularly used in the treatment of avian coccidiosis. Tissue residue of these antibiotics may be found in poultry, we have sought safe alternative anticoccidial herbal materials for the control of avian coccidiosis. Efficacy of extracts from 15 different herbs, including Bupleurum chinese DC, Sophora flavescens Aiton, and Artemisia annua Linne was tested against Eimeria tenella. One-day-old broiler chicks were infected with a USDA reference book of E. tenella, and administered various herbal extracts. Survival rates, lesion scores, body weight gains, bloody diarrhea, and oocysts excretions were investigated at the first and the second week after infection. Bloody diarrhea in the S. flavescens and Sinomenium acutum treated groups was milder than that of the other infected groups. Survival rates in the groups treated with Ulmus macrocarpa (100%), Pulsatilla koreana, Torilis japonica, Artemisia asiatica and S. flavescens (90%) were higher than that of the infected control group (70%). Lesion scores in the groups treated with U. macrocarpa (1.40+/-1.14) or Pulsatilla koreana (1.60+/-1.82) were significantly lower than those of the infected control group (3.00+/-1.10). During the first week after infection, the weight gains in the groups treated with Quisqualis indica (232.9+/-43.5 g), S. flavescens (214.4+/-46.1 g) and S. acutum (211.3+/-29.4 g) were significantly higher than the infected control group (172.4+/-17.6 g). In conclusion, the data of the survival rates, bloody diarrhea symptoms, lesion scores, body weight gains and oocyst excretions indicate that the extract of S. flavescens was the most effective. P. koreana, S. acutum, U. macrocarpa and Q. indica were also effective. Further research on the above herbal materials will be carried out by the authors by chemical analysis of the extracts.

Anti-protozoal efficacy of medicinal herb extracts against Toxoplasma gondii and Neospora caninum.

The purpose of this study was to determine whether alcohol extracts of herbs (Sophora flavescens Aiton, Sinomenium acutum (Thunb.) Rehder and E.H. Wilson, Pulsatilla koreana (Yabe ex Nakai) Nakai ex T. Mori, Ulmus macrocarpa Hance and Torilis japonica (Houtt.) DC.) from South Korea, possess in vitro anti-protozoal activity against cultures of Toxoplasma gondii and Neospora caninum. These herbs have been used as human anti-parasitics in Asian countries for many years. Alcohol extracts of these herbs were serially diluted to final concentrations ranging from 625 to 19.5 ng/ml in media and added to wells containing either T. gondii or N. caninum tachyzoites in equine dermal (ED) cells. Parasite growth inhibition was measured using 3H-uracil incorporation as compared to untreated controls. T. japonica inhibited T. gondii proliferation by 99.3, 95.5, 73.0 and 54.0% in the range from 156 to 19.5 ng/ml, and S. flavescens inhibited T. gondii proliferation by 98.7, 83.0 and 27.2% in the range from 156 to 39 ng/ml. T. japonica inhibited N. caninum proliferation by 97.8, 97.9, 85.3 and 46.4% in the range from 156 to 19.5 ng/ml. S. flavescens inhibited N. caninum proliferation by 98.6, 97.0, 69.5 and 14.0% in the range from 156 to 19.5 ng/ml. Toxicity to host cells was noted when concentrations of T. japonica and S. flavescens exceeded 625 ng/ml. The herb extracts from S. acutum, Pulsatilla koreana, and U. macrocarpa also showed toxicity at higher levels but did not achieve the same inhibition effects at the lower concentrations against T. gondii and N. caninum as T. japonica and S. flavescens.

Anti-protozoal efficacy of high performance liquid chromatography fractions of Torilis japonica and Sophora flavescens extracts on Neospora caninum and Toxoplasma gondii.

We previously reported that alcoholic extracts of Sophora flavescens and Torilis japonica from South Korea demonstrated good efficacy in reducing replication of Toxoplasma gondii and Neospora caninum. To characterize the chemical component associated with anti-protozoal activity, specific fractions were isolated by high performance liquid chromatography (HPLC) and used for in vitro testing. These fractions were evaluated in vitro against T. gondii and N. caninum. Fractions of the herb extracts were serially diluted to final concentrations of 2.850 to 0.356 ng/ml in medium and added to wells containing replicating T. gondii and N. caninum. To determine the ability of each fraction to inhibit parasite proliferation, 3H-uracil incorporation was used to determine parasite replication. In cultures infected with T. gondii, a fraction of T. japonica (TJ2) inhibited T. gondii proliferation by 99.2, 94.4, 88.6 and 27.0% in the range from 2.850 to 0.356 ng/ml. Four fractions of S. flavescens (SF1-SF4) inhibited T. gondii proliferation by 99.6-60.6, 96.9-48.1, 92.3-68.2 and 95.4-52.9% in the range from 2.850 to 0.356 ng/ml. In cultures infected with N. caninum, a fraction of T. japonica (TJ2) inhibited N. caninum proliferation by 98.3, 95.5, 79.7 and 30.6% in the range from 2.850 to 0.356 ng/ml. Four fractions of S. flavescens (SF1-SF4) inhibited N. caninum proliferation by 97.1-25.9, 94.8-35.5, 95.9-33.7 and 95.4-49.4% in the range from 2.850 to 0.356 ng/ml. These fractions of T. japonica and S. flavescens extracts are currently undergoing in vivo evaluation in experimentally infected mice.

Multijet and multistage aerosol concentrator: design and performance analysis.

A multijet and multistage aerosol concentrator was designed and fabricated with two virtual impactors in a series. Collection efficiency, internal loss, and concentration factors were calculated at ambient conditions for each stage. The total inlet flow rate of the aerosol concentrator was set at 1000 L/min(-1), while the minor flow rate for the first stage was at 6.0% of the total inlet flow and the minor flow rate of the second stage was at 6.7% of the first stage minor flow. The aerosol concentrator was calibrated using polystyrene latex particles in aerodynamic sizes ranging from 0.5 to 10 microm. Several configurations of the multijet acceleration nozzles and multitube receptors were designed in this study. The effects of the different designs were subsequently evaluated through experimentation. It was found that a properly designed multijet and multistage aerosol concentrator can significantly improve aerosol concentration performance. Results showed that the concentration factor increases from 1 to 240 over the particle size range studied. Applications of the multijet and multistage aerosol concentrator with high-volume flow rate can vary widely, from detection of biological aerosols at low concentration, laboratory aerosol sampling, clean room monitoring, and ambient aerosol measurements.

Identification of Acanthocephala discovered in changran-pickles and myungran-pickles.

To identify acanthocephala found in 'Changran-pickles' and 'Myungran-pickles' each organ was measured in permanent slides. In the present report, the results obtained were as follows: 1. Morphology of male worms: Worms possessed 18-19 longitudinal rows, with 4 hooks per row, which became smaller towards the base of proboscis. Each worm contained two testis and six cement glands arranged linearly. Body 22.0 by 0.8-0.6 mm and 15.0 by 0.6-0.4 mm, proboscis 284.8 by 227.6 micro m and 524.9 by 151.4 micro m, proboscis sheath 1570.7 by 72.7 micro m and 751.9 by 280.4 micro m, lemnisci length 2566.7 and 1085.6, testis 2202.9-1860.5 by 737.0-575.7 micro m and 1033.8-981.1 by 463.1-351.6 micro m, cement glands 940.2 by 441.2 micro m and 610.0 by 369.1 micro m. 2. Morphology of female worms: Worms possessed 14-18 longitudinal rows, with 6-10 hooks per row and become smaller toward the base of proboscis. Each worm contained an uterine bell and uterus in the posterior portion and the eggs filled the body cavity. Body, approximately 14.0 - 51.0 mm by 0.7-0.5 - 2.2-1.4 mm, proboscis 466.1-268.9 micro m by 259.9-252.0 micro m, proboscis sheath 1550.7-506.0 by 298.8-231.1 micro m, lemnisci length 1325.7-473.1 micro m, eggs approximately 112.4 by 28.5 micro m - 51.7 by 14.0 micro m. In this present study, the acanthocephala collected in 'Changran-pickles' and 'Myungran-pickles' were identified as Echinorhynchus gadi by morphological features.

Urocanic acid-modified chitosan-mediated PTEN delivery via aerosol suppressed lung tumorigenesis in K-ras(LA1) mice.

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Revisiting of aerosol gene delivery may provide an alternative for safe and effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in the previous study was used as a gene carrier. The potential effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) on Akt-related signals and cell cycle regulation were evaluated. Aerosols of UAC-PTEN were delivered into K-ras(LA1) lung cancer model mice through the nose-only inhalation system twice a week for total 4 weeks. Delivered PTEN suppressed lung tumor development significantly through nuclear complex formation between PTEN and p53, suppressing Akt-related signals as well as cell cycle regulation. Together, our results suggest that aerosol delivery of UAC-PTEN may be compatible with noninvasive in vivo gene therapy.

[Incidence of Buxtonella sulcata from cattle in Kyonggi-do].

In order to survey the prevalence of Buxtonella sulcata in Kyonggi-do in 1984 and 1994, the feces of cattle were collected and examined. Of 792 cattle in 1984 and 293 in 1994, cysts of B. sulcata were detected from 266 (33.6%) and 101 (34.5%) cattle respectively. The positive rates were 85.9% and 64.2% in breeder cattle, 44.8% and 9.4% in dairy cattle, 7.5% and 14.9% in Korean cattle and 1.8% in beef cattle. In spring, the cyst positive rates were 62.5% in 1984 and 27.8% in 1994; 20.1% and 66.7% in summer; 21.3% and 0% in autumn; and 34.8% and 64.6% in winter. More cattle, 69.1% (184) and 55.5% (56) in 1984 and 1994, had diarrhea among the cyst positive cattle than those of cyst negative, 37.6% (198) and 32.3% (62).