Search PubMed⌕ Search

Biomedical subjects

S Park

Publications and source records attributed to S Park.

At least 253 records · Page 14Linked to original sources
PubMed1999

Ovarian cancer: loss of heterozygosity frequently occurs in the ATM gene, but structural alterations do not occur in this gene.

Ataxia-telangiectasia is a multisystem recessive disease characterized clinically by cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, sensitivity to radiomimetic agents and an increased predisposition to cancer. This pleiotropic disorder is caused by mutations in the ATM gene, which is located at the human chromosomal region 11q23. Loss of heterozygosity (LOH) at 11q22-q23 is a frequent event in ovarian cancer, suggesting the presence of a tumor suppressor gene in this region. We have found that LOH in the ATM gene occurred in 44% of informative cases in a series of 22 primary ovarian tumors. LOH of this region occurred at the same frequency during the advanced stages (III-IV; 3/9, 33%) as in the early stages (I-II; 4/13, 31%) of ovarian cancer. To investigate the role of ATM in ovarian cancer, we used a PCR-based single-strand conformation polymorphism assay for mutation detection of the entire coding sequence of the ATM gene (65 exons) in 22 ovarian tumors. No somatic alterations of the ATM gene were found in these ovarian cancer samples including those with LOH present in the ATM gene. Our study has identified a region (11q23) which probably contains a frequently altered tumor suppressor gene in ovarian cancer, and this gene does not appear to involve the coding sequences of the ATM gene.

Adenocarcinoma↗
PubMed1999

Enhanced splicing of the first intron from the gonadotropin-releasing hormone (GnRH) primary transcript is a prerequisite for mature GnRH messenger RNA: presence of GnRH neuron-specific splicing factors.

The rat GnRH gene consists of four short exons (denoted 1, 2, 3, and 4) and three introns (A, B, and C). All three introns are spliced from the primary transcript, resulting in a mature mRNA. Northern blot and RT-PCR analyses showed that the GnRH primary transcript and its splicing intermediates are more prevalent than the mature GnRH mRNA in a variety of non-GnRH-producing tissues. To delineate the possible splicing mechanism of introns, an in vitro HeLa splicing system was used. Introns B and C were efficiently spliced, while intron A spanning between exon 1 and exon 2 was not. The retention of intron A was relieved when the 5'- and/or 3'-splice sites of intron A were point mutated based on the consensus sequence. The splicing activity was even more strengthened when a putative branchpoint site was moved to the upstream region of the pyrimidine tract of intron A. Intron A could be partially spliced when whole exons (2, 3, and 4) were linked up with intron A. There are two putative exonic splicing enhancers (ESEs) in exon 3 and exon 4. The ESE on exon 4 (ESE4) is much stronger than that on exon 3. The closer the ESE4 to the 3'-splice site of intron A, the better the splicing activity became. However, in the presence of the nuclear extract from GnRH neurons, there was an enhancement in the splicing activity notwithstanding the distance between ESE4 and 3'-splice site of intron A. These results suggest that the ESE4 functions as both the constitutive and regulated enhancer. Collectively, our study provides evidence that enhanced splicing of intron A by putative GnRH neuron-specific splicing factor(s) interacting with the ESEs is a prerequisite for mature GnRH synthesis.

Animals↗
PubMed1999

Functional roles of the proprioceptive system in the control of goal-directed movement.

This article explored functional roles of the proprioceptive system during the control of goal-directed movements. Proprioceptive information contributes to the control of movement through both reflex and central connections. Spinal and transcortical reflex loops establish a servomechanism which provides automatic corrections of unexpected changes in muscle length and allows compensation for undesirable irregularities in the mechanical properties of muscles by modulating limb stiffness at the subconscious level. Central connections provide the control system with information about peripheral states which is used in voluntary components of movement control. Before the initiation of movement, proprioceptive information about initial limb orientation becomes a basis for the programming of motor commands. During a movement, proprioceptive input about velocities and angular displacements of a limb is used to regulate movement by triggering planned sequences of muscle activation and modulating motor commands. After movement, feedback produced by responses is compared with previously stored information, verifying the quality of the movement. Considering potential roles of the reflex and central connections, the proprioceptive system seems to constitute an important aspect of motor control mechanisms, providing the control system with efficiency and flexibility in the regulation of goal-directed movements.

Biomechanical Phenomena↗
PubMed1999

Expression of Th1 and Th2 type cytokines responding to HBsAg and HBxAg in chronic hepatitis B patients.

The cytokine pattern on viral antigen recognition is believed to exert a profound influence on the resolution of viral infections and viral clearance. This study was initiated to investigate whether a cytokine imbalance oriented toward Th2 type response plays a role in chronic hepatitis B. Cytokine profiles of peripheral blood mononuclear cells associated with chronic hepatitis B were analysed by RT-PCR. Upon HBsAg stimulation, expression of IFN-gamma, IL-2, IL-4, and IL-10 was detected in 41%, 8%, 41%, and 50% of the patients, respectively. Among these cytokines, the expression of IFN-gamma was associated with high levels of serum AST/ALT. However, we could not prove that Th2 type cytokines had a protective effect on hepatocytes. Upon HBxAg stimulation, there was no recognizable association of cytokine patterns with AST/ALT levels. In conclusion, production of a Th1 cytokine, IFN-gamma, by HBsAg-reactive cells was associated with hepatocyte damage in chronic hepatitis B, while no counteracting effect of Th2 cytokines produced by those cells was observed.

Cytokines↗
PubMed1999

T2-weighted fast spin-echo MR findings of adenocarcinoma of the uterine cervix: comparison with squamous cell carcinoma.

The purpose of this study was to investigate the differences in MR findings of adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix and to compare MR findings with pathologic findings. MR images of 17 patients with pathologically proven AC, using a fast spin-echo (FSE) T2-weighted image (T2WI) with pelvic phased-array coil on a 1.5-T unit, were retrospectively evaluated. After measurement of the signal intensity (SI) ratios of the region of interest between tumors and gluteus maximus muscle, we compared the ratios of AC with those of 16 patients with SCC. AC showed relatively high SI on FSE T2WI with multiseptated lesions in four cases and hydrometrocolpos in three cases. The mean SI ratio was 3.82 +/- 1.68 in AC and 2.35 +/- 0.42 in SCC (p < 0.0001, t-test). Multiple tumorous glands with cytoplasmic and intraglandular mucin or serous fluid were pathologically found in AC, but SCC revealed the compact cellularity of stratified squamous tumor cells. The cervical AC showed higher SI than SCC on FSE T2WI with occasional multiseptated lesions and hydrometrocolpos. If the SI ratio of the tumor was more than 3.0, AC could be diagnosed with a sensitivity of 68.8% and a specificity of 100%.

Adenocarcinoma↗
PubMed1999

Full-thickness skin graft from the ulnar aspect of the wrist to cover defects on the hand and digits.

Skin defects on the volar surface of the hand and digits are commonly treated with skin grafts. Many donor sites capable of providing adequate skin have already been reported. Ideal conditions for the donor site depend on skin color, texture, durability, and size. The authors describe the use of a new donor site for harvesting skin grafts to repair relatively small skin defects on the hand and digits. They used full-thickness skin grafts from the ulnar aspect of the wrist to reconstruct burn contractures and syndactyly in 20 patients. Their grafts provided an ideal color and texture match, and normal function of the hand and digits was restored. The donor site was closed directly, and the resulting scar was inconspicuous.

Burns↗
PubMed1999

The Wearable Motherboard: a flexible information infrastructure or sensate liner for medical applications.

Research on the design and development of a Sensate Liner for Combat Casualty Care has led to the realization of the world's first Wearable Motherboard or an "intelligent" garment for the 21st Century. This Georgia Tech Wearable Motherboard (GTWM) provides an extremely versatile framework for the incorporation of sensing, monitoring and information processing devices. The principal advantage of GTWM is that it provides, for the first time, a very systematic way of monitoring the vital signs of humans in an unobtrusive manner. Appropriate sensors have been "plugged" into this motherboard using the developed Interconnection Technology and attached to any part of the individual being monitored, thereby creating a flexible wearable monitoring device. The flexible data bus integrated into the structure transmits the information to monitoring devices such as an EKG Machine, a temperature recorder, a voice recorder, etc. The bus also serves to transmit information to the sensors (and hence, the wearer) from external sources, thus making GTWM a valuable information infrastructure. GTWM is lightweight and can be worn easily by anyone--from infants to senior citizens. GTWM has enormous potential for applications in fields such as telemedicine, monitoring of patients in post-operative recovery, the prevention of SIDS (sudden infant death syndrome), and monitoring of astronauts, athletes, law enforcement personnel and combat soldiers.

Ambulatory Care↗
PubMed1999

Umbilical reconstruction after repair of omphalocele and gastroschisis.

This article presents our technique of umbilical reconstruction after the repair of omphalocele and gastroschisis. We have treated 8 patients with an average follow-up period of 13 months (range, 6 approximately 24 months). No major complications have occurred; minor complications have included delayed wound healing, decreased umbilical depth, and hematoma. Our procedure is especially useful for patients who have a midline abdominal scar and relatively intact bilateral rectus abdominis muscles. Most of the patients and their parents have been satisfied with the results of umbilical reconstruction.

Child↗
PubMed1998

Interpretation of a BMP activity gradient in Drosophila embryos depends on synergistic signaling by two type I receptors, SAX and TKV.

Graded activity of the DPP signaling pathway is critical for specification of dorsal embryonic cell fates in Drosophila. We present evidence that a second BMP ligand, SCW, potentiates DPP activity. Using dominant-negative forms of the type I receptors SAX and TKV, we demonstrate that SAX mediates the SCW signal, while TKV is required for both DPP and SCW activity. We find that while DPP/TKV signaling is obligatorily required, SCW/SAX activity is necessary but not sufficient for dorsal patterning. SAX and TKV act synergistically, suggesting a mechanism for integration of the SCW and DPP signals. Further, we show that the extracellular protein SOG can antagonize SCW, thus limiting its ability to augment DPP signaling in a graded manner.

Animals↗
PubMed1998

Pseudomonas aeruginosa LasD processes the inactive LasA precursor to the active protease form.

LasA and LasD are staphylolytic proteinases which are secreted by the opportunistic pathogen Pseudomonas aeruginosa. We have previously described the purification and characterization of both LasA and LasD, a 21-kDa protein which shares many of the enzymatic properties of LasA. In this follow-up study we describe the isolation of the 42-kDa precursor of LasA (proLasA) and demonstrate the ability of the purified LasD proteinase to cleave the inactive proLasA to the 20-kDa active form of the proteinase.

Bacterial Proteins↗
PubMed1998

Characterization of bovine and human cDNAs encoding NAP-22 (22 kDa neuronal tissue-enriched acidic protein) homologs.

We have characterized the bovine and the human cDNAs encoding the NAP-22 (22 kDa neuronal tissue-enriched acidic protein) homologs. Both bovine and human cDNAs encode proteins of 227 amino acids. The deduced amino acid sequences of the bovine and the human proteins are 63% and 65% identical, respectively, to that of rat NAP-22 protein, strongly suggesting that both the cDNAs characterized encode NAP-22 proteins. They also share 45% and 41% amino acid sequence identities with chicken CAP-23 (23 kDa cytoskeleton associated protein). Several important protein motifs, including myristoylation and phosphorylation sites, are well conserved in sequences and positions in all three mammalian NAP-22 proteins and chicken CAP-23 proteins. The bovine cDNA was characterized further. Southern analysis of the bovine genomic DNA suggests that the bovine NAP-22 protein is encoded by a single-copy gene. RNA blot analysis revealed that the bovine gene for NAP-22 protein encodes a 1.7 kb transcript that is present only in the brain. Our data suggest that the four proteins, bovine and human NAP-22 homologs, rat NAP-22, and chicken CAP-23, have homologous functions in different organisms.

3' Untranslated Regions↗
PubMed1998

Isolation and characterization of a chitinase cDNA from the entomopathogenic fungus, Metarhizium anisopliae.

A novel chitinase gene was isolated from Metarhizium anisopliae grown in a medium containing chitin as the sole carbon source. Comparisons of nucleotide sequence of the isolated gene with those of other fungal chitinase genes showed low sequence identity (24.4-36.4%) except for the active site of chitinase. In addition, molecular mass determination of the fused gene product separated on a gel showed that the fused chitinase seems to be about 70 kDa, while the molecular mass calculated from the deduced amino acid sequence can be about 58 kDa. These molecular masses were different from values of 33 kDa for an endochitinase and 110 kDa for an exochitinase (N-acetylglucosaminidase) from M. anisopliae published previously.

Amino Acid Sequence↗
PubMed1998

Increased repetition blindness in schizophrenia patients and first-degree relatives of schizophrenia patients.

This study investigated the phenomenon of repetition blindness in schizophrenia patients and first-degree relatives of schizophrenia patients. Twelve schizophrenia patients, 13 siblings of schizophrenia patients and 26 normal controls were tested on their ability to detect the repetitions within rapidly presentated visual word lists. Schizophrenics and their relatives showed increased repetition blindness compared with normal controls. This suggests a deficit in rapid information processing in schizophrenia.

Adult↗
PubMed1998

Frequent loss of heterozygosity on the long arm of chromosome 6: identification of two distinct regions of deletion in childhood acute lymphoblastic leukemia.

Cytogenetic analysis of childhood acute lymphoblastic leukemia (ALL) identified nonrandom chromosomal abnormalities of the long arm of chromosome 6. Most of the alterations are deletions that are thought to be indicative of the presence of a tumor suppressor gene that is mutated on the remaining allele. These observations led us to consider whether 6q loss may contribute to the pathogenesis of childhood ALL. To define further a region containing this gene, we analyzed the loss of heterozygosity (LOH) of chromosome 6 in 113 primary ALL samples with matched normal DNA using 34 highly informative microsatellite markers. LOH was found in 17 (15%) samples at one or more of the loci, and partial or interstitial deletions of 6q were detected in 11 of these tumors. On the basis of these results, we performed a detailed deletional map and identified two distinct regions of deletion. The first region is flanked by D6S283 and D6S302 loci at 6q21-22. The second region is flanked by D6S275 and D6S283 loci at 6q21. Clinical analysis determined that LOH of 6q was demonstrated both in precursor-B cell ALLs (15 of 93; 16%) and in T cell ALLs (2 of 19; 11%). In addition, 19 patients have been studied at diagnosis and relapse; 18 showed the same 6q21-22 structural abnormality at relapse (normal, 16 patients; LOH, 2 patients) as their initial presentation, suggesting, albeit with a small patient sample size, that 6q21-22 deletions may be an initial event in leukemogenesis and may occur less frequently during the progression of childhood ALL. These data suggest the presence of putative tumor suppressor genes on chromosome arm 6q that are important in the development of both T and precursor-B childhood ALLs. Our map provides important information toward cloning putative ALL tumor suppressor genes.

Child↗
PubMed1998

Tertiary structural changes in the cleft containing the ATP sensitive tryptophan and reactive thiol are consistent with pivoting of the myosin heavy chain at Gly699.

The conformation of myosin subfragment 1 (S1) in the vicinity of the ATP sensitive tryptophan (Trp510) and the highly reactive thiol (SH1), both residing in the "probe-binding" cleft at the junction of the catalytic and lever arm domains, was studied to ascertain its role in the mechanism of energy transduction and force generation. In glycerinated muscle fibers in rigor, a fluorescent probe linked to SH1 detects a strained probe-binding cleft conformation following a length transient by altering emission intensity without detectably rotating. In myosin S1 in solution, the optical activity of Trp510 senses conformation change in the probe-binding cleft caused by substrate analog trapping of S1 in various structures attainable transiently during normal energy transduction. Also in S1 in solution, the induced optical activity of a fluorescein probe linked to SH1 shows sensitivity to changing probe-binding cleft conformation caused by nucleotide binding to the S1 active site. The changes in the optical activity of Trp510 and SH1 bound fluorescein in response to nucleotide or nucleotide analog binding are interpreted structurally using the S1 crystallographic coordinates and aided by a model of energy transduction that pivots at Gly699 to change probe-binding cleft conformation and to displace the S1 lever arm as during force generation. The crystallographic structure of the probe-binding cleft in S1 resembles most the nucleotide bound conformation in the native protein. A different structure, generated by pivoting at Gly699, better resembles the native rigor conformation of the probe-binding cleft. Pivoting at Gly699 rotates probes at SH1 suggesting that length transients on fibers in rigor do not cause pivoting at Gly699 or reverse the power stroke.

Adenosine Triphosphate↗
PubMed1998

Inhibition of fos-jun-DNA complex formation by dihydroguaiaretic acid and in vitro cytotoxic effects on cancer cells.

The effect of dihydroguaiaretic acid (DHGA), isolated from the aryls of Myristica fragrans, on the transcription factor (fos-jun dimer) action was investigated via in vitro assay. DHGA showed an inhibitory effect against the complex formation of the fos-jun dimer and the DNA consensus sequence with an IC50 value of 0.21 micromol. Nordihydroguaiaretic acid (NDGA) and curcumin also inhibited fos-jun dimer action showing IC50 values of 7.9 and 6.9 nmol, respectively. DHGA and NDGA suppressed leukemia, lung cancer and colon cancer in an in vitro bioassay. The in vitro experiment suggested that inhibition of fos-jun-DNA complex formation could be due to the direct interference of fos-jun dimer binding onto the DNA consensus sequence by NDGA and curcumin.

Dimerization↗