Biomedical subjects

K Sun

Publications and source records attributed to K Sun.

At least 37 records · Page 2Linked to original sources

PubMed2003

Organization of apatite crystals in human woven bone.

The organization of collagen fibrils differs in woven bone and lamellar bone, and it reflects certain aspects of the nature of the mineral crystals associated with them. In order to investigate the morphology and distribution of apatite crystals in woven bone, mineralized collagen fibrils and isolated crystals from the mid-diaphyses of human fetal femurs were observed with scanning and transmission electron microscopy and high-resolution electron microscopy. A number of features of woven bone were observed for the first time by these means. Similar to mature crystals from lamellar bone, the apatite crystals in woven bone are also platelet-shaped. However, most likely because of a high rate of old bone resorption and new bone formation in woven material, the average crystal dimensions are considerably smaller than those of mature crystals in lamellar bone. Apatite crystals were noted on the surface of collagen fibrils in woven bone. In densely packed woven bone, the periodicity of mineral deposited on individual fibrils is in registration over many fibrils. In addition to their association with collagen surfaces, crystals also appear distributed in both extrafibrillar and intrafibrillar collagen regions. In both cases, the minerals are crystalline and defect-free. These characteristics provide insight into the spatial and temporal relation between collagen and mineral that is the basis for the structure and organization of the mineral comprising human woven bone.

Apatites↗

PubMed2003

AnyHeart: a single-piece heart-saving implantable artificial heart (BVAD)--monitoring and estimation.

AnyHeart is a single-piece, implantable biventricular assist device. This electromechanical BVAD has a moving-actuator mechanism. To monitor the status of AnyHeart from anywhere at any time, a portable personal digital assistant (PDA) monitor and web-based remote monitoring system were developed. The PDA local monitoring system has replaced bulky personal computer monitoring systems. The web-based remote monitoring system has several functions such as data collecting, storing, and posting through the internet. Basically, interventricular pressure (IVP) is a parameter indicating the filling level of the blood chambers of AnyHeart. The pump output can be estimated using IVP, which is acquired noninvasively from AnyHeart. With the proposed method, we can estimate the pump output with a small margin of error.

Computers, Handheld↗

PubMed2003

Applications of the pulsatile flow versatile ECLS: in vivo studies.

INTRODUCTION: T-PLS (Twin-Pulse Life Support) is the first commercial pulsatile ECLS (Extra Corporeal Life Support) device (1). The dual sac structure of T-PLS can effectively reduce high membrane oxygenator inlet pressure and hemolysis. To verify both the use of T-PLS for ECLS and the advantages of T-PLS, we tested various models. METHOD AND RESULTS: In the partial CPB (cardio pulmonary bypass) model (swine), T-PLS (N = 6), and Biopump (N = 2), a single pulsatile pump (N = 2), were compared. In the case of single pulsatile flow, during pump systole, pressure increased to 700 - 800 mmHg at the inlet port of the membrane oxygenator. fHb, a hemolysis measurement value, was about 80 mg/dL at 3 hours. On the contrary, because of T-PLS's dual sac system, the pressure of T-PLS had a maximum value of about 250 mmHg and fHb was similar to that of the commercial centrifugal pumps. In the total CPB model (bovine, N = 6), the heart was stopped via cardioplegia (Kcl). T-PLS flow was maintained at 3.0-4.5 L/min. T-PLS functioned like a natural heart, having a pulse pressure of 26-43 mmHg and a pulse rate of 40-60 bpm (beats per minute). In the emergency case model (canine, N = 6), T-PLS was started 10 minutes after cardiac arrest from electronic shock. In spite of cardiac arrest for a period of 40 minutes, the heart was recovered after defibrillation. In the ARDS (Acute Respiratory Distress Syndrome) model (canine, N = 6), minimal ventilator parameters were set: tidal volume 130 ml, respiration rate = bpm, FiO2 = 10%. Three hours after starting T-PLS, PO2 of the carotid artery blood (after 2 hours: 195 +/- 89.4; after 3 hours: 258 +/- 99.3 mmHg) was above half the value of the femoral artery but was within normal range. CONCLUSION: It is suggested that a portable pulsatile ECLS like T-PLS may be used as a CPB device and as an alternative CPR (cardiopulmonary resuscitation) device in the case of cardiac arrest. Due to the pulsatile flow, oxygenated blood is delivered to the patient without overloading the ARDS patients heart.

Animals↗

PubMed2003

Efficacy of CVD risk factor modification in a lower-middle class community in Pakistan: the Metroville Health Study.

The Metroville Health Study aimed to reduce consumption of total cooking fats by 33%, salt by 25% and replace ghee with vegetable oil in a lower middle class urban community in Pakistan. Households (n=403) were randomly assigned to Intervention and Control groups. A baseline screening collected data on CVD risk factors, knowledge and attitudes and household consumption of cooking fats and salt. Intervention households received information about CVD and regular visits by social workers who measured cooking fats and salt and counselled cooks on the goals of intervention. Two years later, 291 households were re-screened. Intervention households reduced consumption of fats and salt compared to differences were total fat, 48% (p<0.0001); ghee, 37% (p=0.005); vegetable oil, 33% (p=0.0001); and salt, 41% (p=0.011). Household visits by trained social workers were effective in achieving reductions in consumption of cooking fat and salt in a lower class urban community.

Cardiovascular Diseases↗

PubMed2003

TrialDB: A web-based Clinical Study Data Management System.

Clinical Study Data Management Systems (CSDMSs) are a class of software that support centralized management of data generated during the conduct of clinical studies. Commercial CSDMSs include Oracle Clinical, ClinTrial and MetaTrial. Such systems, which are typically deployed at an institutional or organizational level, must accommodate diverse types of data from different clinical domains that is generated by different groups of clinical investigators. Large-scale CSDMSs typically employ a high-end database engine that is usually accessed over an intranet or the Internet using Web-based technologies. CSDMSs in institution-wide use for a variety of clinical domains are best served by entity-attribute-value (EAV) modeling for the clinical data: all the commercial CSDMSs that we are aware of use EAV design. However, de novo development of EAV databases for data management is a challenging task. A large body of generic metadata-driven code must be developed before a basic EAV application can be written. Clearly, the availability of pre-existing software with the requisite functionality would be very valuable. We will discuss the benefits of such software being in open-source form.

Clinical Trials as Topic↗

PubMed2002

Postnatal development of 11beta-hydroxysteroid dehydrogenase type 1 in the rat hippocampus.

Glucocorticoids (GCs) have important actions in the hippocampus of the brain, where their access to glucocorticoid receptor (GR) is increased by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). 11beta-HSD1 converts biologically inactive 11-dehydrocorticosterone into active corticosterone. However, the postnatal development of 11beta-HSD1 in the hippocampus is not properly understood. In this study, the postnatal distribution and development of 11beta-HSD1 in the hippocampus of the rat brain was studied with immunohistochemistry and Western blot analysis. Results showed that abundant 11beta-HSD1 immunoreactive substance (ir-11beta-HSD1) was present in the hippocampus. There were homogeneous distributions of 11beta-HSD1 in the hippocampal CA1, CA2, CA3, CA4 regions and the dentate gyrus at postnatal days 1, 3, and 7. Interestingly, the developmental distribution of GR in the hippocampus followed the same pattern as 11beta-HSD1. Western blot analysis demonstrated that a higher level of expression of 11beta-HSD1 in the hippocampus was found in the first 2 weeks of life. The expressions of 11beta-HSD1 started to drop to adult levels at about postnatal day 15 both in the hippocampus and in other brain areas. These results suggest that the higher expression of 11beta-HSD1 in the neonatal hippocampus may be important for the maturation of the central nervous system mediated by GCs through GR.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

PubMed2002

Application of the moving-actuator type pump as a ventricular assist device: in vitro and in vivo studies.

A moving actuator type pump has been developed as a multifunctional Korean artificial heart (AnyHeart). The pump consists of a moving actuator as an energy converter, right and left sacs, polymer (or mechanical) valves, and a rigid polyurethane housing. The actuator containing a brushless DC motor moves back and forth on an epicyclical gear train to produce a pendular motion, which compresses both sacs alternately. Of its versatile functions of ventricular assist device and total artificial heart use, we have evaluated the system performance as a single or biventricular assist device through in vitro and in vivo experiments. Pump performance and anatomical feasibility were tested using various animals of different sizes. In the case of single ventricular assist device (VAD) use, one of the sacs remained empty and a mini-compliance chamber was attached to either an outflow or inflow port of the unused sac. The in vitro and in vivo studies show acceptable performance and pump behavior. Further extensive study is required to proceed to human application.

Animals↗

PubMed2001

Microscopic self-organization in networks.

We report our numerical studies on microscopic self-organization of a reaction system in three types of differently connected networks: a regular network, a small-world network, and a random network. Our simulation results show that the topology of the network has an important effect on the communication among reaction molecules, and plays an important role in microscopic self-organization. The correlation length among reacting molecules in a random or a small-world network is much shorter compared with that in a regular one. As a result, it is much easier to obtain microscopic self-organization in a small-world or a random network. We also observed a phase transition from a stochastic state to a synchronized state when we increased the randomness of a small-world network.

Journal Article↗

PubMed2001

A Saccharomyces servazzii clone homologous to Saccharomyces cerevisiae chromosome III spanning KAR4, ARS 304 and SPB1 lacks the recombination enhancer but contains an unknown ORF.

In order to learn about the evolutionary conservation of the recombination enhancer (RE) that controls donor preference during mating type switching in Saccharomyces cerevisiae, we have cloned a 13 kb region from S. servazzii. We find that the order of four genes surrounding the RE in S. cerevisiae (PRD1, KAR4, SPB1 and PBN1) is preserved in S.servazzii. However, there is an additional ORF in S. servazzii between PRD1 and KAR4 that is not homologous to any gene in S. cerevisiae or to genes in other organisms. Despite a 75-79% amino acid identity for KAR4 and SPB1, respectively, the S. servazzii sequence did not carry a well-conserved RE sequence and these sequences lacked RE function when introduced into S. cerevisiae. The S. servazzii region contains a sequence that supports autonomous DNA replication in S. cerevisiae and may represent a homologue of ARS304. The S. servazziii sequence has Genbank Accession No. BankIt359091 AF307954.

Amino Acid Sequence↗

PubMed2001

Two consecutive zinc fingers in Sp1 and in MAZ are essential for interactions with cis-elements.

The zinc finger proteins Sp1 and Myc-associated zinc finger protein (MAZ) are transcription factors that control the expression of various genes. Regulation of transcription by these factors is based on interactions between GC-rich DNA-binding sites (GGGCGG for Sp1 and GGGAGGG for MAZ) and the carboxyl-terminal zinc finger motifs of the two proteins. Sp1 and MAZ have three and six zinc fingers, respectively, and the details of their interactions with cis-elements remain to be clarified. We demonstrate here that Sp1 and MAZ interact with the same GC-rich DNA-binding sites, apparently sharing DNA-binding sites with each other. We found that the DNA binding activities of Sp1 and MAZ depended mainly on consecutive zinc fingers, namely the second and third zinc fingers in Sp1 and the third and fourth zinc fingers in MAZ. Furthermore, the interactions of the zinc finger proteins with the same cis-elements appear to play a critical role in the regulation of gene expression. It seems plausible that two consecutive zinc finger motifs in a zinc finger protein might be essential for interaction of the protein with DNA.

3T3 Cells↗

PubMed2001

Independent repression of a GC-rich housekeeping gene by Sp1 and MAZ involves the same cis-elements.

The transcription factors Sp1 and MAZ (Myc-associated zinc finger protein) contain several zinc finger motifs, and each functions as both a positive and a negative regulator of gene expression. In this study, we characterized the extremely GC-rich promoter of the human gene for MAZ, which is known as a housekeeping gene. Unique symmetrical motifs in the promoter region (nucleotides -383 to -334) were essential for the expression of the gene for MAZ, whereas an upstream silencer element (nucleotides -784 to -612) was found to act in a position-dependent but orientation-independent manner. Sp1 and MAZ bound to the same cis-elements in the GC-rich promoter, apparently sharing DNA-binding sites. The relative extent of binding of Sp1 and MAZ to these cis-elements corresponded to the extent of negative regulation of the expression of the gene for MAZ in various lines of cells. Furthermore, novel repressive domains in both Sp1 (amino acids 622-788) and MAZ (amino acids 127-292) were identified. Suppression by Sp1 and suppression by MAZ were independent phenomena; histone deacetylases were involved in the autorepression by MAZ itself, whereas DNA methyltransferase 1 was associated with suppression by Sp1. Our results indicate that both deacetylation and methylation might be involved in the regulation of expression of a single gene via the actions of different zinc finger proteins that bind to the same cis-elements.

Animals↗

PubMed2001

Characterization and promoter analysis of the mouse gene for transcription factor Sp4.

Transcription factor Sp4 is a member of the Sp1 family. It functions differently from other members of this family, such as Sp1 and Sp3, and the gene for Sp4 is transcribed in a tissue-specific manner. Recent studies in mice suggest that Sp4 might play an important role in growth, viability, and male fertility. We report here the isolation and characterization of the gene for Sp4 from a mouse genomic library. The mouse gene for Sp4 was about 80 kb in length and it consisted of six exons and five introns. The promoter was found in a CpG island and had a high G+C content. The proximal promoter contained multiple putative binding sites for the transcription factors Sp1 and MAZ but lacked a consensus TATA box. Multiple sites for the initiation of transcription were mapped in a GC-rich region from 286 bp to 211 bp upstream of the ATG triplet at the site of initiation of translation, and all of the sites were either C or G. Transfection experiments and deletion analysis allowed us to localize the promoter to a region that was no more than 93 bp upstream from the first site of initiation of transcription. We also found that ectopic expression of Sp1 and of MAZ, but not of Sp3, suppressed expression of the Sp4 promoter in a dose-dependent manner.

Amino Acid Sequence↗

PubMed2001

Identification of mouse Jun dimerization protein 2 as a novel repressor of ATF-2.

A mouse cDNA that encodes a DNA-binding protein was identified by yeast two-hybrid screening, using activating transcription factor-2 (ATF-2) as the bait. The protein contained a bZIP (basic amino acid-leucine zipper region) domain and its amino acid sequence was almost identical to that of rat Jun dimerization protein 2 (JDP2). Mouse JDP2 interacted with ATF-2 both in vitro and in vivo via its bZIP domain. It was encoded by a single gene and various transcripts were expressed in all tested tissues of adult mice, as well as in embryos, albeit at different levels in various tissues. Furthermore, mouse JDP2 bound to the cAMP-response element (CRE) as a homodimer or as a heterodimer with ATF-2, and repressed CRE-dependent transcription that was mediated by ATF-2. JDP2 was identified as a novel repressor protein that affects ATF-2-mediated transcription.

3T3 Cells↗

PubMed2001

Improved calcification resistance and biocompatibility of tissue patch grafted with sulfonated PEO or heparin after glutaraldehyde fixation.

A novel chemical modification of biological tissues was developed aimed at improving biocompatibility and calcification resistance. This method involved the additional grafting of sulfonated PEO (PEO-SO(3)) or heparin after conventional glutaraldehyde (GA) fixation of bovine pericardium (BP). The amino groups of PEO-SO(3) or heparin were utilized to react to the GA residues to block them. The PEO-SO(3) or heparin grafted tissues demonstrated a slightly higher shrinkage temperature and tensile strength, but greater resistance to collagenase digestion, than GA treated ones. These results suggest that modified tissues have improved durability due to the grafting and filling effect of PEO-SO(3) or heparin in addition to the GA cross-linking. At the direct contact cytotoxicity test in vitro, PEO-SO(3) or heparin grafted tissue was shown to be nontoxic, while relatively significant cytotoxicity was observed for the GA treated tissues, possibly due to the release of GA. From the in vivo calcification study, calcium contents deposited on the modified tissues were much less than those on GA treated tissues. Such a decreased calcification might be explained by the decrease of residual GA groups during the additional treatment, and the space-filling effect and the nonadhesive property and/or the blood compatibility of PEO-SO(3) or heparin grafted covalently. The newly modified tissue patch was observed to show improved pathological assessibility including less inflammation and tissue reactions. This simple modification method may be useful for calcification-resistant and blood-compatible tissue patches for cardiovascular implants.

Animals↗

PubMed2001

The Stat3/5 locus encodes novel endoplasmic reticulum and helicase-like proteins that are preferentially expressed in normal and neoplastic mammary tissue.

The signal transducers and activators of transcription (STAT) 5 and 3 are critical for mammary alveolar development during pregnancy and remodeling during involution. In the mouse, STAT3, STAT5a, and STAT5b are encoded by adjacent genes on chromosome 11 (60.5 cM). To identify additional genes in the Stat3/5 locus that may participate in normal and neoplastic development of the mammary gland, we have cloned and sequenced 500 kb and searched for genes preferentially expressed in mammary tissue. We identified six known genes and cloned two new genes, termed D11Lgp1 and D11Lgp2. Both genes are most highly expressed in normal mammary tissue and mammary tumors from several transgenic mouse models. LGP1 consists of 532 and 530 amino acids in mouse and human, respectively (88% similarity). A region in the carboxy-terminal half of LGP1 has limited homology with Arabidopsis thaliana GH3-like proteins. Immunofluorescence studies demonstrated that LGP1 is located in the nuclear envelope and the endoplasmic reticulum. LGP2 is a cytoplasmic protein of 678 amino acids.

Amino Acid Sequence↗

PubMed2001

A simple and secure technique for tracheal T-tube insertion.

We describe a simple and secure technique for the insertion of a long Montgomery type T-tube in patients with tracheal stenosis. An endotracheal tube is placed into the lumen of the T-tube and by maintaining the airway during insertion, the technique has been found to be safe and it can prevent the kind of tracheal damage occurring with blind techniques.

Humans↗

PubMed2001

Loss of E-cadherin expression in gastric intestinal metaplasia and later stage p53 altered expression in gastric carcinogenesis.

Gastric cancers are commonly subdivided into intestinal and diffuse subtypes on a morphologic basis, supported by corollary evidence of differences at the pathogenetic and molecular levels. Chronic atrophic gastritis with intestinal metaplasia is a common precursor lesion for the intestinal type of carcinoma. To identify early molecular changes, in this study we have examined 13 surgical specimens both for the expression of E-cadherin, p53 and beta-catenin by immunohistochemistry and for methylation of the CDH1 promoter (E-cadherin) by bisulfite genomic sequencing of laser capture microdissected samples. Each specimen examined contained areas of normal (nonmetaplastic) gastric mucosa, as well as areas of intestinal metaplasia and/or carcinoma. Reduced or absent E-cadherin and partial to complete methylation of one to multiple CpG sites examined in the CDH1 promoter were observed in all of the metaplasia samples. Thus, the methylation status of the CDH1 promoter and expression of E-cadherin together provide strong evidence that loss of E-cadherin is an early event in intestinal type gastric carcinogenesis. In contrast, expression of p53, assumed to be mutant p53, was generally not detected (except for isolated cells) until the carcinoma stage in tissues from these patients. These results suggest that mutation of p53 is a late event in intestinal type gastric cancer. The level of beta-catenin expression did not appear to change between normal, metaplastic and carcinoma cells of intestinal type, and no nuclear staining was visible in any of the tissues. These results suggest that the Wnt signaling pathway is not upregulated in this type of cancer.

Adenocarcinoma↗

PubMed2001

Diagnosis of carotid artery atheroma by magnetic resonance imaging.

Atheroma appears as a very low signal intensity area on 2-dimensional time-of-flight (TOF) magnetic resonance (MR) images, and its components have various signal intensities on spin-echo (SE) images. The present study investigated atheroma of the carotid arteries in 37 subjects with risk factors (63+/-10 years of age; 19 men) by magnetic resonance imaging (MRI). On 2-dimensional (2D) TOF images, the carotid arteries were clearly demonstrated in all cases and atheroma was detected in 23 patients. The most common location of atheroma was at the origin of the internal carotid artery. There was vascular remodeling in all patients with atheroma. 2D-TOF images showed 97% agreement with ultrasonography. SE images clearly demonstrated atheroma in all 23 patients with atheroma. All patients with atheroma showing high signal intensity on T1-weighted images had hyperlipidemia. These findings indicate that the 2D-TOF imaging method is useful for detecting atheroma and SE-images are useful for its characterization.

Aged↗