Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 559 records · Page 31Linked to original sources

PubMed1999

SAS4 and SAS5 are locus-specific regulators of silencing in Saccharomyces cerevisiae.

Sir2p, Sir3p, Sir4p, and the core histones form a repressive chromatin structure that silences transcription in the regions near telomeres and at the HML and HMR cryptic mating-type loci in Saccharomyces cerevisiae. Null alleles of SAS4 and SAS5 suppress silencing defects at HMR; therefore, SAS4 and SAS5 are negative regulators of silencing at HMR. This study revealed that SAS4 and SAS5 contribute to silencing at HML and the telomeres, indicating that SAS4 and SAS5 are positive regulators of silencing at these loci. These paradoxical locus-specific phenotypes are shared with null alleles of SAS2 and are unique among phenotypes of mutations in other known regulators of silencing. This work also determined that these SAS genes play roles that are redundant with SIR1 at HML, yet distinct from SIR1 at HMR. Furthermore, these SAS genes are not redundant with each other in silencing HML. Collectively, these data suggest that SAS2, SAS4, and SAS5 constitute a novel class of regulators of silencing and reveal fundamental differences in the regulation of silencing at HML and HMR. We provide evidence for a model that accounts for the observation that these SAS genes are both positive and negative regulators of silencing.

Alleles↗

PubMed1999

Specific expression of heat shock protein HspA2 in human male germ cells.

In the mouse, the heat shock protein 70-2 (Hsp70-2) has been found to play a critical role in spermatogenesis. The HspA2 gene is the human homologue of the murine Hsp70-2 gene with 91.7% identity in the nucleotide coding sequence. We examined the expression of HspA2 in human tissues. To detect HspA2 expression, antiserum 2A that was raised against mouse Hsp70-2 and that cross-reacted with human HspA2 protein expressed in Escherichia coli was used. The results of Western blotting indicate that significant HspA2 expression occurs in testes with normal spermatogenesis, whereas only a low amount of HspA2 was expressed in testis with Sertoli cell-only syndrome. Only a small amount of HspA2 was detected in breast, stomach, prostate, colon, liver, ovary, and epididymis. Immunoreactivity to HspA2 was present in spermatocytes and spermatids in the testes with normal spermatogenesis, while immunoreactivity to HspA2 in testis with Sertoli cell-only syndrome was remarkably decreased or inconspicuous over the entire cell. These results demonstrate that the HspA2 protein is highly expressed in human male specific germ cells, suggesting that HspA2 protein may play a specific role during meiosis in human testes as found in the murine model.

Amino Acid Sequence↗

PubMed1999

Unilateral renal cystic disease in adults.

Unilateral renal cystic disease (URCD) is morphologically indistinguishable from autosomal dominant polycystic kidney disease (ADPKD) except for its unilaterality. Unlike ADPKD, URCD patients show neither a genetic background nor progressive deterioration in renal function; thus, the differential diagnosis of URCD from ADPKD is important. Only a few cases of URCD have been reported. This study reports two cases of URCD in adults together with a literature review. We identified these two cases using abdominal computerized tomography and family screening with renal ultrasonography.

Adult↗

PubMed1999

The clinical usefulness of F-18 FDG coincidence PET without attenuation correction and without whole-body scanning mode in pulmonary lesions comparison with CT, MRI, and clinical findings.

PURPOSE: This study was undertaken to assess the clinical usefulness of fluorine-18 flurodeoxyglucose (F-18 FDG) coincidence detection (CoDe) positron emission tomography (PET) of various lung lesions by comparing it with CT, MRI, and clinical findings. MATERIALS AND METHODS: Forty-two patients with pulmonary lesions underwent CoDe PET using a dual-head gamma camera equipped with a 5/8 inch thick NaI (Tl) crystals. The patients were prepared for the study by overnight fasting. Data was acquired at approximately 1 hour after the intravenous injection of 111 to 370 MBq (3 to 10 mCi) of F-18 FDG. A spinal scan of the thorax was performed using a slip ring gantry for 30 minutes. After rebinning, routine tomographic slices were reconstructed without attenuation correction and the images were analyzed visually. RESULTS: Pathologic diagnoses and staging were obtained at surgery in nine patients; in the remaining 33 patients, aspiration cytology was available. CoDe PET detected all 35 pathologically proved malignant lesions. In nine patients who underwent surgery, seven CoDe PET studies corresponded with pathologic staging, whereas in six of the nine patients, CT and MRI corresponded with the pathologic findings. Seven patients also had benign lesions that showed FDG uptake. CONCLUSIONS: F-18 FDG CoDe PET was sensitive in the evaluation of lung lesions but was not specific for malignancy. F-18 FDG CoDe PET was more sensitive than CT and MRI in nodal staging in the limited number of patients studied thus far.

Aged↗

PubMed1999

Supratentorial ependymomas in adult patients.

OBJECTIVE: Ependymomas arise from different areas in the neuraxis and have variable outcomes that depend on tumor location and patient age at the time of presentation. The predictive value of histology for these tumors is unresolved. We report a series of adult patients with supratentorial ependymomas to characterize the roles of surgery, histology, ploidy, and proliferation index in tumor control. METHODS: Fourteen of the 23 supratentorial ependymomas were in the region of the third ventricle and the remainder were located in the hemispheres. Resections were gross total in 12 patients, subtotal in 8, and biopsy in 3. A single pathologist reviewed all slides and quantitated the deoxyribonucleic acid. The mean follow-up duration was 95 months (+/-75 mo). RESULTS: All of the malignant ependymomas were hemispheric (n = 4). Mortality occurred only in patients with third ventricular tumors; two patients died as a result of surgical complications and three as a result of tumor progression. Kaplan-Meier estimates of 5- and 10-year survival rates were 100% for hemispheric and 72.5% for third ventricular tumors (62.5% including the two perioperative deaths). The median time to recurrence was 53 months, with a 10-year progression-free survival rate of 27%. Univariate analysis revealed that recurrence was associated with malignant histology, including mitoses, cellularity, and aneuploidy. For nonmalignant ependymomas, recurrence was associated with subtotal resection and metastases. S-phase fraction did not correlate with recurrence. Only malignant histology correlated with recurrence on multivariate analysis. CONCLUSION: Although the numbers are too small to draw any definite conclusions, treatment of ependymomas that arise in the supratentorial compartment in adult patients results in excellent outcomes despite frequent recurrences. Association with the third ventricle and metastases seem to have a negative impact on survival, whereas malignant histology, subtotal resection, and metastases may be predictors of recurrence.

Adolescent↗

PubMed1999

Human cytomegalovirus IE1 protein activates AP-1 through a cellular protein kinase(s).

During human cytomegalovirus (HCMV) infection, a rapid increase in AP-1 activity is detected. In this study, activation of transcription from promoters containing AP-1-binding sites by the IE1 protein of HCMV was examined. In transient transfection assays with reporter plasmids, it was found that IE1 strongly induced AP-1-driven transcription. Cells stably expressing IE1 also showed higher levels of AP-1 activity than did control cells. IE1 expression did not raise levels of c-jun and c-fos RNA, as determined by quantitative RT-PCR. AP-1 induction by IE1 was blocked efficiently by protein kinase inhibitors in a cell type-dependent manner; for example, by staurosporine in the human microglial cell line U373MG and by H7 in the human promonocytic cell line U937. IE1-driven activation of AP-1 was increased dramatically by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 (MEKK1). The results of this study indicate that IE1 activates AP-1 at the post-transcriptional level and that MEKK1 may play an important role in this process.

Cells, Cultured↗

PubMed1999

Multistability analysis of phase locking patterns in an excitatory coupled neural system.

We quantitatively analyze the multistability of dynamic patterns of a bursting neural system with diffusive coupling. Through effective coupling analysis, we show that the system is not in-phase locking but exhibits various phase locking patterns, each of which corresponds to the stable fixed points of the effective coupling. The simulation proves the validity of the effective coupling method in analyzing the multistability of neural systems which presents complicated dynamic patterns such as bursting.

Computer Simulation↗

PubMed1999

Effects of time-delayed interactions on dynamic patterns in a coupled phase oscillator system.

We investigate the effects of time delayed interactions in the network of neural oscillators. We perform the stability analysis in the vicinity of a synchronized state at vanishing time delay and present a related phase diagram. In the simulations it is shown that time delay induces various phenomena such as clustering where the system is spontaneously split into two phase locked groups, synchronization, and multistability. Time delay effects should be considered both in the natural and artificial neural systems whose information processing is based on the spatiotemporal dynamic patterns.

Journal Article↗

PubMed1999

Parameter dependence of stochastic resonance in the stochastic Hodgkin-Huxley neuron.

Recently, the phenomena of stochastic resonance (SR) have attracted much attention in the studies of the excitable systems under inherent noise, in particular, nervous systems. We study SR in a stochastic Hodgkin-Huxley neuron under Ornstein-Uhlenbeck noise and periodic stimulus, focusing on the dependence of properties of SR on stimulus parameters. We find that the dependence of the critical forcing amplitude on the frequency of the periodic stimulus shows a bell-shaped structure with a minimum at the stimulus frequency, which is quite different from the monotonous dependence observed in the bistable system at a small frequency range. The frequency dependence of the critical forcing amplitude is explained in connection with the firing onset bifurcation curve of the Hodgkin-Huxley neuron in the deterministic situation. The optimal noise intensity for maximal amplification is also found to show a similar structure.

Animals↗

PubMed1999

Crystallization and preliminary X-ray crystallographic studies of the D2 region of the skeletal muscle ryanodine receptor.

The N-terminal portion (amino acids 1303-1367) of the type 1 ryanodine receptor D2 region is thought to be critical for excitation-contraction coupling in skeletal muscle. A segment of the D2 region (amino acids 1317-1355) was expressed as a glutathione S-transferase fusion protein (GST-D2) and then crystallized at room temperature using ammonium sulfate as precipitant. Using a newly developed cryo-soaking method, complete native data sets were measured to a resolution of 2.2 A using synchrotron radiation. The crystal was found to be hexagonal, belonging to space group P6(3)22, with unit-cell parameters a = b = 116.1, c = 77.9 A.

Animals↗

PubMed1999

Cytoplasmic expression of hepatitis B core antigen in chronic hepatitis B virus infection: role of precore stop mutants.

AIMS/BACKGROUND: The cytoplasmic expression of HBcAg is a possible target of immune hepatocytolysis and it is important for the pathogenesis of hepatic injury in chronic hepatitis B virus (HBV) infection. Cytoplasmic HBcAg expression has been suggested to be related to the precore sequence of HBV, HBV DNA level or cell cycle of hepatocytes and the aim of this study was to understand its mechanism. MATERIAL/METHODS: We studied the expression pattern of HBcAg and its relationship to serum HBV DNA levels, cell proliferation activity of hepatocytes and precore mutation using 66 patients' sera and biopsied liver specimens of chronic hepatitis B. RESULTS: The expression patterns of HBcAg were cytoplasmic predominant (CP) in 17 cases, nuclear and cytoplasmic (NC) in 10 cases and nuclear predominant (NP) in 9 cases and negative in 30 cases. CP expression cases showed a higher grade of hepatitis activity than NP expression cases. Serum HBV DNA levels showed a wide range and there was no significant difference according to the expression pattern of HBcAg. Cell proliferation activity of hepatocytes, measured by Ki-67 (MIB-1) labelling index was higher in CP expression cases than in NP expression cases and it was also significantly higher in cases of high grade than in low grade hepatitis activity. The precore region was evaluated by primer extension assay in 51 cases and there were 16 cases of 1896 precore mutant, 23 cases of wild type, 12 cases of mixed infection of 1896 precore mutant type and wild type. CP expression of HBcAg was significantly more frequent in 1896 precore mutant cases (86%) than in wild type cases (26%). CONCLUSION: CP expression of HBcAg is the major pattern of 1896 precore mutant cases and it might be involved in the severe liver injury of precore mutants. One of the mechanisms regulating CP HBcAg expression is suggested to be precore mutation of HBV as well as cell cycle of hepatocyte.

Adult↗

PubMed1999

Decrease in incidence of gestational diabetes mellitus in Far North Queensland between 1992 and 1996.

The pregnant population in Far North Queensland is at high risk of medical complications, such as diabetes, compared to the general Australian population (1,2). This retrospective observational study shows a true decline in the incidence of gestational diabetes mellitus (GDM) in this region over a 5-year period (1992-1996), contradicting the current belief that the incidence of GDM is increasing in non-Caucasian Australians. Although this change may be due to an improvement in medical and/or dietary intervention in this region, the real cause for the decline is yet to be recognized.

Adult↗

PubMed1999

Two-effective-source method for the calculation of in-air output at various source-to-detector distances in wedged fields.

A simple algorithm was developed for calculation of the in-air output at various source-to-detector distances (SDDs) on the central axis for wedged fields. In the algorithm we dealt independently with two effective sources, one for head scatter and the other for wedge scatter. Varian 2100C with 18 and 8 MV photon beams was used to examine this algorithm. The effective source position for head scatter for wedged fields was assumed to be the same as that for open fields, and the effective source position for wedge scatter was assumed to be a certain distance upstream from the physical location of the wedge. The shift of the effective source for wedge scatter, w, was found to be independent of field size. Moreover, we observed no systematic dependency of w on wedge angle or beam energy. One value, w = 5.5 cm, provided less than 1% difference in in-air outputs through the whole experimental range, i.e., 6 x 6 to 20 x 20 cm2 field size (15 x 20 cm2 for 60 degrees wedge), 15 degrees-60 degrees wedge angle, 80-130 cm SDD, and both 18 and 8 MV photon beams. This algorithm can handle the case in which use of a tertiary collimator with an external wedge makes the field size for the determination of wedge scatter different from that for head scatter. In this case, without the two-effective-source method, the maximum of 4.7% and 2.6% difference can be given by the inverse square method and one-effective-source method in a 45 degrees wedged field with 18 MV. Differences can be larger for thicker wedges. Enhanced dynamic wedge (EDW) fields were also examined. It was found that no second effective source is required for EDW fields.

Algorithms↗

PubMed1999

Dosimetric characteristics of a double-focused miniature multileaf collimator.

The dosimetric characteristics of a double-focused miniature multileaf collimator (mMLC) attached to a Philips SL75/5 linear accelerator (linac) have been investigated. Output factors, percentage depth-dose, penumbra, leaf transmission, and leakage between the leaves were measured for the 6 MV x-ray beam on this accelerator. Because leakage both through and between the leaves is minimal, the linac jaws can be kept fixed while the mMLC leaf configuration is modified for different aperture shapes. This allows for accurate output prediction using the equivalent square formalism. Percent depth-dose measured for fields defined by the mMLC show little deviation from the percent depth-dose measured for fields defined by the machine jaws or Lipowitz metal blocks. Because the mMLC matches beam divergence in both directions, allows minimal beam transmission, and has a large source-to-collimator distance, the penumbra is sharper for fields defined by the mMLC than for fields defined by the linac jaws or Lipowitz metal blocks. Based on these data, dose calculations for mMLC-defined fields can be applied with no change in procedures from those used for fields defined using conventional methods.

Radiotherapy Planning, Computer-Assisted↗

PubMed1999

Generation of neutralizing human monoclonal antibodies against parvovirus B19 proteins.

Infections caused by human parvovirus B19 are known to be controlled mainly by neutralizing antibodies. To analyze the immune reaction against parvovirus B19 proteins, four cell lines secreting human immunoglobulin G monoclonal antibodies (MAbs) were generated from two healthy donors and one human immunodeficiency virus type 1-seropositive individual with high serum titers against parvovirus. One MAb is specific for nonstructural protein NS1 (MAb 1424), two MAbs are specific for the unique region of minor capsid protein VP1 (MAbs 1418-1 and 1418-16), and one MAb is directed to major capsid protein VP2 (MAb 860-55D). Two MAbs, 1418-1 and 1418-16, which were generated from the same individual have identity in the cDNA sequences encoding the variable domains, with the exception of four base pairs resulting in only one amino acid change in the light chain. The NS1- and VP1-specific MAbs interact with linear epitopes, whereas the recognized epitope in VP2 is conformational. The MAbs specific for the structural proteins display strong virus-neutralizing activity. The VP1- and VP2-specific MAbs have the capacity to neutralize 50% of infectious parvovirus B19 in vitro at 0.08 and 0.73 microgram/ml, respectively, demonstrating the importance of such antibodies in the clearance of B19 viremia. The NS1-specific MAb mediated weak neutralizing activity and required 47.7 micrograms/ml for 50% neutralization. The human MAbs with potent neutralizing activity could be used for immunotherapy of chronically B19 virus-infected individuals and acutely infected pregnant women. Furthermore, the knowledge gained regarding epitopes which induce strongly neutralizing antibodies may be important for vaccine development.

Amino Acid Sequence↗

PubMed1999

C/EBPbeta (NF-M) is essential for activation of the p20K lipocalin gene in growth-arrested chicken embryo fibroblasts.

The p20K gene is induced in conditions of reversible growth arrest in chicken embryo fibroblasts (CEF). This expression is dependent on transcriptional activation and on a region of the promoter designated the quiescence-responsive unit (QRU). In this report, we describe the regulatory elements of the QRU responsible for activation in resting cells and characterize the trans-acting proteins interacting with these elements. We show that the QRU consists of functionally distinct domains including quiescence-specific and weak proliferation-responsive elements. The quiescence responsiveness of the QRU was mapped to two C/EBP binding sites, and the activity of the p20K promoter and its QRU was inhibited by the expression of a dominant negative mutant of C/EBPbeta in nondividing cells. The activation of QRU in response to serum starvation and contact inhibition correlated with the presence of a growth arrest-specific complex in electrophoretic mobility shift assays. This complex was supershifted by antibody for C/EBPbeta. C/EBPbeta accumulated in conditions of contact inhibition as a result of transcriptional activation. Therefore, C/EBPbeta was itself regulated as a growth arrest-specific gene in CEF. Finally, we show that the expression of p20K is regulated by linoleic acid, an essential fatty acid binding to p20K. The addition of linoleic acid to contact-inhibited CEF markedly repressed the synthesis of p20K without inducing mitogenesis. The activity of the QRU was inhibited by linoleic acid or the peroxisome proliferator-activated receptor PPARgamma2 in transient expression assays. Therefore, we have identified C/EBPbeta as a key activator of a growth arrest-specific gene in CEF and implicated an essential fatty acid, linoleic acid, in regulation of the QRU and the p20K lipocalin gene.

Animals↗

PubMed1999

Two-dimensional reaction of biological molecules studied by Weighted-Ensemble Brownian dynamics.

Computer simulations offer critical insights into the reaction of biological macromolecules, especially when the molecular shapes are too complex to be amenable to analytical solution. In this work, the Weighted-Ensemble Brownian (WEB) Dynamics simulation algorithm is adapted to a reaction of two unlike biological molecules, with the interaction modeled by a two-parameter system: a spherical molecular depositing on a target region of an infinite cylinder with a periodic boundary conditions. The original algorithm of Huber and Kim is streamlined for this class of reactive models. The reaction rate constant is calculated as a function of relative sizes of the reactive to non-reactive regions of the cylindrical molecule. An analytical expression for the rate constant is also obtained from the solution of the diffusion equation for the special case of a constant-flux boundary condition. Good agreement between analytical and simulation results validates the applicability of WEB Dynamics to a reaction of molecules of complicated shape. On the other hand, the simple form of our analytical expression is useful as a testing case for other simulation and numerical techniques.

Algorithms↗

PubMed1999

Thresholds for cellular disruption and activation of the stress response in renal epithelia.

Renal ischemia causes a rapid fall in cellular ATP, increased intracellular calcium (Ca(i)), and dissociation of Na(+)-K(+)-ATPase from the cytoskeleton along with initiation of a stress response. We examined changes in Ca(i), Na(+)-K(+)-ATPase detergent solubility, and activation of heat-shock transcription factor (HSF) in relation to graded reduction of ATP in LLC-PK(1) cells to determine whether initiation of the stress response was related to any one of these perturbations alone. Ca(i) increased first at 75% of control ATP. Triton X-100 solubility of Na(+)-K(+)-ATPase increased below 70% control ATP. Reducing cellular ATP below 50% control consistently activated HSF. Stepped decrements in cellular ATP below the respective thresholds caused incremental increases in Ca(i), Na(+)-K(+)-ATPase solubility, and HSF activation. ATP depletion activated both HSF1 and HSF2. Proteasome inhibition caused activation of HSF1 and HSF2 in a pattern similar to ATP depletion. Lactate dehydrogenase release remained at control levels irrespective of the degree of ATP depletion. Progressive accumulation of nonnative proteins may be the critical signal for the adaptive induction of the stress response in renal epithelia.

Adenosine Triphosphate↗