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Biomedical subjects

Y Ko

Publications and source records attributed to Y Ko.

At least 19 recordsLinked to original sources
PubMed2005

Effects of oral administration of insulin-like growth factor-I on circulating concentration of insulin-like growth factor-I and growth of internal organs in weanling mice.

Insulin-like growth factor (IGF)-I is a polypeptide that mediates the growth-promoting action of growth hormone in postnatal animals. The present study was conducted to examine whether orally administered IGF-I would be absorbed into the general circulation and also whether ingested IGF-I would enhance the growth of whole body as well as internal organs, and tissues in 3-week-old ICR-strain female weanling mice. In experiment (Exp) 1, a total of 70 mice received IGF-I orally at 1 microg.g-1 in 0.2-ml PBS or the vehicle alone. Concentrations of IGF-I and glucose in heart blood were measured after killing 5 animals in each group every fourth hour during a 24-hour period. In Exp 2, a total of 40 mice received oral IGF-I administration at 1 microg.g-1 or vehicle every third day beginning from day 0 for a 13-day period. Half the animals were killed at day 7 and the other half at day 13. Weights of whole body and organs/tissues (small intestine, liver, thigh muscle, and brain) were measured every day and at slaughter, respectively. In Exp 1, following the oral IGF-I administration, serum IGF-I concentration increased at hour 4 (p<0.01) and returned to the hour 0 level by hour 8, whereas glucose concentration was lowest at hour 4 and returned to the hour 0 level by hour 16. In the PBS-fed group, neither IGF-I nor glucose concentration changed during the 24-hour period. In Exp 2, weight of small intestine increased (p<0.05) in response to the oral IGF-I, whereas weights of liver and thigh muscle of the IGF-I-fed group were greater (p<0.01) and tended to be greater (p=0.06), respectively, than those of the PBS-fed only at day 13. However, brain weight and serum concentrations of IGF-I and IGF-II were not affected by oral IGF-I administration. Results suggest that although orally administered IGF-I mainly acts at the intestine, a portion of ingested IGF-I is absorbed into the general circulation to enhance the growth of selective organs/tissues in weanling mice.

Animals↗
PubMed2005

High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study.

BACKGROUND: Combination chemotherapy can cure patients with non-Hodgkin's lymphoma (NHL), but those who suffer treatment failure or relapse still have a poor prognosis. High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) can improve the outcome of these patients. We evaluated an intensified high-dose sequential chemotherapy program with a final myeloablative course. PATIENTS AND METHODS: Inclusion criteria were age 18-65 years, histologically proven primary progressive or relapsed aggressive NHL and eligibility for HDCT. The therapy consists of two cycles DHAP: dexamethasone 40 mg (day 1-4), high-dose cytarabine 2 g/m2 12q (day 2), cisplatin 100 mg/m2 (day 51); patients with partial (PR) or complete remission (CR) received cyclophosphamide 4 g/m2 (day 37), followed by peripheral blood stem cell (PBSC) harvest; methotrexate 8 g/m2 (day 1) plus vincristine 1.4 mg/m2 (day 51); and etoposide 500 mg/m2 (day 58-62). The final myeloblative course was BEAM: cytarabine 200 mg/m2 12q (day 81-84), etoposide 150 mg/m2 12q (day 81-84), melphalan 140 mg/m2 (day 80), carmustin 300 mg/m2 (day 80) followed by PBSCT. RESULTS: Fifty-seven patients (median age 43 years, range 24-65) were enrolled: 23 (40%) patients were refractory to primary therapy and 34 (60%) patients had relapsed NHL. The response rate (RR) after 2 cycles of DHAP was 72% (9% CR, 63% PR) and at the final evaluation (100 days post transplantation) 43% (32% CR, 11% PR). Toxicity was tolerable. Median follow-up was 25 months (range 1-76 months). Freedom from second failure (FF2F) and overall survival (OS) at 2 years were 25% and 47% for all patients, respectively. FF2F at 2 years for patients with relapse and for patients refractory to primary therapy were 35% and 9% (P=0.0006), respectively. OS at 2 years for patients with relapse and for patients refractory to primary therapy were 58% and 24% (P=0.0044), respectively. CONCLUSIONS: We conclude that this regimen is feasible, tolerable and effective in patients with relapsed NHL. In contrast, the results in patients with progressive disease are unsatisfactory. This program is currently being modified by addition of rituximab for patients with relapsed aggressive NHL.

Adolescent↗
PubMed2005

Expression and relationship of the insulin-like growth factor system with posthatch growth in the Korean Native Ogol chicken.

Insulin-like growth factors (IGF) act as regulators that modulate proliferation and differentiation of various cells. Also, IGF are involved in metabolism and body growth by regulating the synthesis and degradation of glycogen and proteins in animals. However, the effect of IGF system on body growth in poultry including Korean Native Ogol chickens (KNOC) has not been thoroughly studied. Therefore, this study was performed to investigate the expressions of IGF system and the relationship of IGF with body growth during posthatch growth in KNOC. Sera and organs were collected at hatch and at 1, 3, 5, and 7 wk. The mRNA expressions of IGF, IGF-I receptor, and IGF binding protein (IGFBP)-2 were quantitatively analyzed by reverse transcription (RT)-PCR. The IGF concentrations were measured by heterologous RIA, and the expression of IGFBP-2 was detected by Western ligand blotting. The body weight of KNOC rapidly increased during the experimental period, and increase in breast muscle weight was 5-fold from 1 to 3 wk. Although the circulating IGF-I concentration gradually increased, the level of IGF-I in breast muscle rapidly declined during growth period. The IGF-II expression was not similar to IGFBP-2 during postnatal growth. Moreover, the breast muscle IGF-II concentration was mainly correlated with body growth at 7 wk and breast muscle IGF-I at 1 and 5 wk. Taken together, the present study suggested that the endocrine manner of IGF-I was more important than auto/paracrine actions in body growth of KNOC and that expression of IGF-II was involved in body growth and IGF-I during posthatch growth of KNOC.

Animals↗
PubMed2005

[Surgical repair of isolated anomalous origin of left pulmonary artery from the ascending aorta in a 2-month-old infant].

A 2-month-old infant was referred to our department for evaluation of a congestive heart failure. The chest X-ray showed an enlarged globular heart. Further work-up was consistent with an anomalous origin of left pulmonary artery (PA) from the ascending aorta. The patient underwent a corrective surgery using cardiopulmonary bypass. The left PA was arising 15 cm above the aortic annulus and coursed in the curved manner to the left, crossing the main PA where the media of both vessels were fused. The ligamentum arteriosus, running from the top of the main PA to the right aortic arch, was divided. The left PA was detached at its origin and anastomosed to the main PA. The anterior wall of the main PA, where the media was fused, was reinforced with polytetrafluoroethylene (PTFE) patch. An angiogram 6 months after operation showed a rapid antegrade flow to the left PA, and angiographically normal luminal contour.

Anastomosis, Surgical↗
PubMed2004

Challenges to environmental toxicology and epidemiology: where do we stand and which way do we go?

Modern toxicology investigates a wide array of both old and new health hazards. Priority setting is needed to select agents for research from the plethora of exposure circumstances. The changing societies and a growing fraction of the aged have to be taken into consideration. A precise exposure assessment is of importance for risk estimation and regulation. Toxicology contributes to the exploration of pathomechanisms to specify the exposure metrics for risk estimation. Combined effects of co-existing agents are not yet sufficiently understood. Animal experiments allow a separate administration of agents which can not be disentangled by epidemiological means, but their value is limited for low exposure levels in many of today's settings. As an experimental science, toxicology has to keep pace with the rapidly growing knowledge about the language of the genome and the changing paradigms in cancer development. During the pioneer era of assembling a working draft of the human genome, toxicogenomics has been developed. Gene and pathway complexity have to be considered when investigating gene-environment interactions. For a best conduct of studies, modern toxicology needs a close liaison with many other disciplines like epidemiology and bioinformatics.

Animals↗
PubMed2004

Reliability of non-invasively acquired human genomic DNA as a substrate for real-time PCR-assisted analysis of genetic polymorphisms.

Molecular epidemiological studies require high numbers of participants. The combination of an non-invasive access to human DNA with a rapid genotyping analysis, e.g. by use of LightCycler assisted real-time polymerase chain reaction (PCR), can be helpful in conducting such trials. The aim of our study was to define, for the first time, the use of LightCycler technology in analysis of non-invasively derived DNA. DNA extracted from blood, mouthwash and buccal cytobrush samples from 100 volunteers was analyzed for the genotypes of cytochrome P450 CYP1B1, and glutathione S-transferases GSTT1, GSTM1 and GSTP1. The median amounts of DNA isolated from blood, mouthwash and buccal cytobrush samples were 95, 11 and 8 microg, respectively. While genotyping for CYP1B1 codon 432 polymorphism and GSTP1 codon 105 polymorphism resulted in a complete correspondence for all three modes of sampling, the identification of individuals with null-genotype for GSTT1 or GSTM1 failed in some cases due to atypical courses of the corresponding melting curves, leading to high false-positive rates in the group of non-invasively derived samples. Thus, the results presented here call for caution in using LightCycler assisted real-time PCR in non-invasively collected samples, at least when appropriate control strategies are not implemented.

Adult↗
PubMed2004

Relationship between egg productivity and insulin-like growth factor-I genotypes in Korean native Ogol chickens.

Endocrine factors, such as steroid hormones and growth factors, regulate egg productivity in terms of the quantity of egg production, egg weight, sexual maturity, and the number of small yellow follicles (SYF). Insulin-like growth factors (IGF) are involved in the regulation of ovulation rate and ovarian follicular development in chickens, and a relationship between IGF-I genotype and egg weight has been reported. However, the effect of IGF on egg productivity in Korean Native Ogol chickens (KNOC) has been little studied. Therefore, this study was conducted to identify the relationship among endocrine factors (IGF-I, IGF-II, estradiol, and progesterone), IGF-I genotypes, and egg productivity. Frequencies of IGF-I genotypes (AA, AB, BB) were 17.3, 26.9, and 55.8%, respectively, within a population. When compared with the IGF-I genotypes, the AB genotype had the highest serum levels of estradiol and progesterone at 40 and 30 wk of age, respectively; the highest IGF-II concentration in F1 follicles at 60 wk; and was positively associated with the number of SYF at 60 wk. The results showed that the A allele was associated with a higher IGF-II expression in the follicles and stimulated the development of follicles, indicating a positive association of the A allele with egg production and the number of SYF. Therefore, these results suggest that there is a possibility of IGF-I genotypes acting as a genetic marker for egg productivity of KNOC.

Aging↗
PubMed2003

Recombinant human erythropoietin, epoetin beta, in patients with relapsed lymphoma treated with aggressive sequential salvage chemotherapy--results of a randomized trial.

The aim of the study was to investigate the effects of erythropoietin (epoetin beta) on red blood cell (RBC) transfusions, hemoglobin (Hb) levels, and quality of life (QOL) in patients with relapsed lymphoma treated with an aggressive sequential salvage chemotherapy (SSCT) regimen. Sixty patients with early or late relapsed Hodgkin's disease ( n=39) or first relapse of aggressive non-Hodgkin's lymphoma ( n=21) were randomized to receive epoetin beta 10,000 IE subcutaneously three times a week or no epoetin during salvage chemotherapy. Patients in both study arms received two cycles of DHAP (dexamethasone, high-dose cytarabine, cisplatin); patients in partial remission (PR) or complete remission (CR) then received cyclophosphamide, followed by peripheral blood stem cell (PBSC) harvest, methotrexate plus vincristine, and etoposide. The final myeloablative course was BEAM (carmustine, etoposide, cytarabine, and melphalan) followed by autologous stem cell support. The primary endpoint of the study was the number of RBC units needed during SSCT. In addition, Hb levels and QOL were measured. The mean number of RBC units given in the epoetin beta arm was 4.5 compared to 8.3 in the control arm ( P=0.0134). The mean Hb levels during therapy were 10.4 g/dl in the epoetin beta arm and 9.7 g/dl in the control ( P=0.018). From baseline until BEAM therapy QOL (EORTC QLQ C30) and fatigue (MFI) assessment showed little QOL worsening or stable levels in both arms with a steeper increase of fatigue levels in the control group. Patients with relapsed lymphoma undergoing aggressive chemotherapy and stem cell support benefited from epoetin beta therapy, with a decrease of RBC transfusion requirements and lower rise of fatigue levels.

Adult↗
PubMed2003

Genetic polymorphisms of cytochrome P450 19 and 1B1, alcohol use, and breast cancer risk in Korean women.

A case-control study was performed to assess the potential influence of CYP19 Arg(264)Cys and CYP1B1 Leu(432)Val polymorphisms on breast cancer risk in a series of Korean breast cancer patients and controls. The results suggest that the CYP19 Arg(264)Cys polymorphism modifies breast cancer risk (OR=1.5, 95% CI=1.1-2.2), especially in association with alcohol consumption (P for interaction=0.04), whereas the CYP1B1 Leu(432)Val polymorphism appears to play no role here.

Adult↗
PubMed2003

Delayed-onset pineal abscess following transsphenoidal surgery for pituitary adenoma: a case report.

A 41-year-old woman suffered fever, speech disturbance and confusion four months after transsphenoidal surgery for pituitary macroadenoma. Meanwhile, the patient had been well except for transient asymptomatic postoperative pneumocephalus without cerebrospinal fluid (CSF) rhinorrhoea. Brain computed tomographic scan revealed a peripherally enhancing pineal abscess which superimposed on a preexisting pineal cyst. CSF findings showed elevated leukocyte count and positive bacterial culture. Three weeks of intensive antibiotic therapy and surgical evacuation of the pineal abscess ensued. The patient showed restricted postoperative recovery with moderate hypothalamic dysfunction. A unique case of delayed-onset postoperative pineal abscess which complicates the preexisting asymptomatic pineal cyst is presented and the possible explanation for this is speculated with review of the available literatures.

Abscess↗
PubMed2002

[Recurrent spontaneous hemorrhage in a patient with light chain immunocytoma].

The 48-year-old female patient was sent to our clinic for further evaluation of a spontaneous decrease of prothrombin- and prolongation of the bleeding-time. She presented in good conditions with an enlargement of cervical lymphnodes and the history of a monoclonal plasmacyte dyscrasia. The laboratory results revealed a pronounced decrease of prothrombin-time, a prolonged activated partial thromboplastin-time, a decrease of factor VII and X activity and a light chain paraprotein. The histological examination of the bone marrow led to the diagnosis of an immunocytoma and a medullar amyloidosis. For the aim of influencing the coagulopathy the patient was treated with chemotherapy. However, she developed severe bleedings. Further haemostaseological tests presented an amyloidosis-associated decrease of factor VII and X, an acquired von Willebrands disease, an acquired thrombozytopathy and a lupus-like anticoagulans. Under substitution of factor VIII-von Willebrand-factor-complex and chemotherapeutic treatment a stabilisation over several years was achieved till the patient died due to an amyloid-associated acute pancreatitis.

Amyloidosis↗
PubMed2002

A method for the rapid construction of cRNA standard curves in quantitative real-time reverse transcription polymerase chain reaction.

Quantification of nucleic acids, especially of mRNA, is increasingly important in biomedical research. The recently developed quantitative real-time polymerase chain reaction (PCR) - a highly sensitive technology for the rapid, accurate and reproducible quantification of gene expression - offers major advantages over conventional quantitative PCR. Transcript quantification is performed in the exponential phase of the PCR reaction through extrapolation of fluorescence signals from a standard calibration curve which represents the initial copy number for a given fluorescence signal. We have developed a method for gene transcript quantification which is based on a LightCycler - assisted real-time PCR in combination with a simple and rapid approach for the construction of external cRNA standards with identical gene sequences as the target gene. Synthesis of cRNAs was performed by in vitro transcription with T7 RNA polymerase followed by reverse transcription and real-time PCR. We applied this approach for transcript quantification of eukaryotic initiation factor 3 p110 (EIF3S8) mRNA in normal testicular tissue. We also present a rapid and simple strategy for the construction of cRNA standards for use in real-time PCR.

Adult↗
PubMed2001

Association of CYP1B1 codon 432 mutant allele in head and neck squamous cell cancer is reflected by somatic mutations of p53 in tumor tissue.

Tobacco use is causally associated with head and neck squamous cell cancer (HNSCC). Here, we present the results of a case-control study that investigated the effects that the genetic variants of the cytochrome (CYP)1A1, CYP1B1, glutathione-S-transferase (GST)M1, GSTT1, and GSTP1 genes have on modifying the risk of smoking-related HNSCC. Allelisms of the CYP1A1, GSTT1, GSTM1, and GSTT1 genes alone were not associated with an increased risk. CYP1B1 codon 432 polymorphism was found to be a putative susceptibility factor in smoking-related HNSCC. The frequency of CYP1B1 polymorphism was significantly higher (P < 0.001) in the group of smoking cases when compared with smoking controls. Additionally, an odds ratio (OR) of 4.53 (2.62-7.98) was discovered when investigating smoking and nonsmoking cases for the susceptible genotype CYP1B1*2/*2, when compared with the presence of the genotype wild type. In combination with polymorphic variants of the GST genes, a synergistic-effect OR was observed. The calculated OR for the combined genotype CYP1B1*2/*2 and GSTM1*2/*2 was 12.8 (4.09-49.7). The calculated OR for the combined genotype was 13.4 (2.92-97.7) for CYP1B1*2/*2 and GSTT1*2/*2, and 24.1 (9.36-70.5) for the combination of CYP1B1*2/*2 and GSTT1-expressors. The impact of the polymorphic variants of the CYP1B1 gene on HNSCC risk is reflected by the strong association with the frequency of somatic mutations of the p53 gene. Smokers with susceptible genotype CYP1B1*2/*2 were 20 times more likely to show evidence of p53 mutations than were those with CYP1B1 wild type. Combined genotype analysis of CYP1B1 and GSTM1 or GSTT1 revealed interactive effects on the occurrence of p53 gene mutations. The results of the present study indicate that polymorphic variants of CYP1B1 relate significantly to the individual susceptibility of smokers to HNSCC.

Alleles↗
PubMed2001

[Chronic progressive polycythemia and thrombocytosis].

The 73-year-old female patient presented with chronic progressive erythrocytosis diagnosed 5 years ago which now is accompanied by thrombocytosis. She complains about generalised itching, pain in distal limbs and shows marked plethora. Having excluded major causes of secondary erythrocytosis the diagnosis was polycythaemia vera with a typical constellation of symptoms, findings and course of disease. Under treatment with 5-Hydroxyurea and repeated phlebotomy thrombocyte count and haematocrit normalised and the patient recovered her usual vitality. Limb pain, itching and plethora disappeared.

Aged↗
PubMed2001

The gap-junctional protein connexin40 is elevated in patients susceptible to postoperative atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF), a cardiac arrhythmia arising from atrial re-entrant circuits, is a common complication after cardiac surgery, but the proarrhythmic substrate underlying the development of postoperative AF remains unclear. This study investigated the hypothesis that altered expression of connexins, the component proteins of gap junctions, is a determinant of a predisposition to AF. METHODS AND RESULTS: The expression of the 3 atrial connexins-connexins 43, 40, and 45-was analyzed at the mRNA and protein levels by Northern and Western blotting techniques and immunoconfocal microscopy in right atrial appendages from patients with ischemic heart disease who were undergoing coronary artery bypass surgery. Twenty percent of the patients subsequently developed AF, which allowed retrospective division of the samples into 2 groups, non-AF and AF. Connexin43 and connexin45 transcript and protein levels did not differ between the groups. However, connexin40 transcript and protein were expressed at significantly higher levels in the AF group. Connexin40 protein was markedly heterogeneous in distribution. CONCLUSIONS: Atrial myocardium susceptible to AF is distinguished from its nonsusceptible counterpart by elevated connexin40 expression. The heterogeneity of connexin distribution could give rise to different resistive properties and conduction velocities in spatially adjacent regions of tissue, which become enhanced and, hence, proarrhythmic the higher the overall level of connexin40.

Aged↗
PubMed2001

Real-time genotyping of cytochrome P4501A1 A4889G and T6235C polymorphisms.

Single nucleotide polymorphisms, such as the cytochrome P450 1A1 (CYP1A1) A4889G and T6235C variants, have been reported to be associated with an increased cancer risk. In order to study their role in molecular-epidemiological studies, we developed a single-step procedure for genotyping these two CYP1A1 polymorphisms using real-time polymerase chain reaction (PCR) and subsequent melting curve analysis. Genotypes of 300 unrelated Caucasians, without prior history of cancer, were determined by real-time PCR and compared to genotypes obtained by restriction fragment length polymorphism PCR. In the population examined, the allele frequency of the CYP1A1 G allele at position 4889 was 0.042, and the frequency of the T allele at position 6235 was 0.10. Five percent of samples disagreed between methods. Sequence analysis of discordant samples revealed that the differences are likely attributed to incomplete digestion of amplicons by the RFLP method. These findings confirm the reliability and utility of real-time PCR as a method for large-scale genotyping.

Adult↗
PubMed2001

Right ventricular dynamic cardiomyoplasty for the univentricular heart with pulmonary hypertension.

OBJECTIVES: We conducted an acute experimental study to test the feasibility of dynamic cardiomyoplasty in a setting of modified Fontan procedure for univentricular heart with pulmonary hypertension to obtain a possible proxy for high-risk Fontan candidates. METHODS: After electrical preconditioning of the left latissimuss dorsi for 6 weeks in 8 dogs, the right ventricular cavity was totally obliterated with concomittent closure of the tricuspid valve and right pulmonary artery. Modified Fontan circulation was established with the aortic homograft anastomosed between the right atrium and pulmonary trunk, incorporated with a pericardial pouch as a compression chamber (neoright ventricle) fixed onto the epicardial surface of the ventricle. After cardiopulmonary bypass termination, a latissimus dorsi was applied to wrap the pericardial pouch and ventricle clockwise and stimulated with a trained-pulse (25 Hz) at 1:1 synchronization ratio with cardiac beats. RESULTS: Profound right heart failure was noted during Fontan circulation in increased pulmonary vascular resistance (11 +/- 3.2 Wood units), whereas graft pacing showed significant augmentation of systolic pulmonary pressure by 54 +/- 12%, the mean pulmonary flow by 68 +/- 23%, and aortic pressure by 23 +/- 5% at a physiological range of central venous pressure (13.2 +/- 0.7 mmHg). Right heart function curve analysis confirmed marked augmentation of right heart performance, restoring almost normal pulmonary circulation. These functional benefits were sustained up to 4 hours in 4 animals until experiments were terminated. CONCLUSIONS: Dynamic cardiomyoplasty in a modified Fontan procedure is a viable surgical option for univentricular heart, not a Fontan candidate.

Animals↗