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Biomedical subjects

J Shin

Publications and source records attributed to J Shin.

At least 19 recordsLinked to original sources
PubMed2003

Unique structural features of a BCL-2 family protein CED-9 and biophysical characterization of CED-9/EGL-1 interactions.

The interactions between B-cell lymphoma 2 (BCL-2) family members are known to be mediated through the binding of the BH3 domain of a proapoptotic member to the BH3-binding groove of an antiapoptotic member. We determined the crystal structure of antiapoptotic CED-9, which reveals a unique C-terminal helix altering the common BH3-binding region. A coexpression system to produce CED-9 in complex with proapoptotic EGL-1 enabled us to show that the binding of EGL-1 to CED-9 is extremely stable, raising the melting temperature (T(M)) of CED-9 by 25 degrees C, and that the binding surface of CED-9 extends beyond the BH3-binding region and reaches the BH4 domain. Consistently, the T(M) and a 1H-15N correlation NMR spectrum of CED-9 in complex with EGL-1 are drastically different from those of CED-9 in complex with the EGL-1 BH3 peptide. The data suggest that the recognition between other BCL-2 family members may also involve much wider protein surfaces than is previously thought.

Animals↗
PubMed2003

Acute diarrhea in Paraguayan children population: detection of rotavirus electropherotypes.

Group A rotavirus infections were detected in 93 of 410 fecal samples from children with acute diarrhea, admitted in three main hospitals of Asunción, Paraguay, from August 1998 to August 2000. Most of the rotavirus-infected patients were admitted during the winter season in the three epidemic years. The rotavirus infection rate was highest in infants from 6 to 23 months of age. In the 93 samples examined, 10 different rotavirus electropherotypes were recognized, but two of them largely predominated. Only one sample showed a short electropherotype pattern, thus indicating a minor involvement of the rotavirus subgroup I in rotaviral acute diarrhea in the area and the time during which the survey was carried out.

Acute Disease↗
PubMed2002

Intussusception in an adult patient with severe hyperglycaemia--a case report.

AIMS: To report a case of adult intussusception associated with and possibly induced by acute hyperglycaemia. METHODS: We present the first case report of adult intussusception with severe hyperglycaemia. Clinical and laboratory data together with radiological findings are presented with a brief review of the literature. RESULTS: A 20-year-old man with no past medical history presented with abdominal pain for 2 days. The patient was severely hyperglycaemic with blood glucose of 72.7 mmol/l (normal 3.3-6.1 mmol/l), a pH of 7.2 and serum potassium of 6.5 mmol/l (normal 3.5-5.0 mmol/l). He had a computed tomography (CT) scan of the abdomen that revealed small bowel intussusception. Upon treatment of his hyperglycaemia, the patient's abdominal pain completely resolved. Follow up abdominal CT revealed complete resolution of the previously detected intussusception. CONCLUSION: Clinicians should be aware of the potential for the occurrence of intussusception in severely hyperglycaemic patients. Correction of hyperglycaemia could lead to resolution of the intussusception without surgical intervention. Possible effects of hyperkalaemia and/or acidosis on gastrointestinal motility should also be considered.

Abdominal Pain↗
PubMed2001

Molecular cloning and characterization of PELP1, a novel human coregulator of estrogen receptor alpha.

Nuclear hormone receptors (NRs) are transcription factors whose activity is regulated by ligands and by coactivators or corepressors. We report the characterization of a new NR coregulator: proline-, glutamic acid-, leucine-rich protein 1 (PELP1), a novel human protein that comprises 1,282 amino acids and is localized on chromosome 17. The primary structure of PELP1 consists of several motifs present in most transcriptional regulators including nine NR-interacting boxes (LXXLL motifs), a zinc finger, and glutamic acid- and proline-rich regions. We demonstrate that PELP1 is a coactivator of estrogen receptor alpha (ERalpha). PELP1 enhances 17beta-estradiol-dependent transcriptional activation from the estrogen response element in a dose-dependent manner. PELP1 interacts with ERalpha and also with general transcriptional coactivators p300 and cAMP response element-binding protein-binding protein. PELP1 was differentially expressed in various human and murine tissues with the highest expression levels in the testes, mammary glands, and brain. We also provide evidence supporting the developmental regulation of PELP1 expression in murine mammary glands, the detectable expression of PELP1 in human mammary cancer cell lines, and the enhanced expression of PELP1 in human breast tumors. These findings suggest that PELP1 is a novel coregulator of ERalpha and may have a role in breast cancer tumorigenesis.

Amino Acid Sequence↗
PubMed2001

Solution structure of the dimeric cytoplasmic domain of syndecan-4.

The syndecans, transmembrane proteoglycans which are involved in the organization of cytoskeleton and/or actin microfilaments, have important roles as cell surface receptors during cell-cell and/or cell-matrix interactions. Since previous studies indicate that the function of the syndecan-4 cytoplasmic domain is dependent on its oligomeric status, the conformation of the syndecan-4 cytoplasmic domain itself is important in the understanding of its biological roles. Gel filtration results show that the syndecan-4 cytoplasmic domain (4L) itself forms a dimer stabilized by ionic interactions between peptides at physiological pH. Commensurately, the NMR structures demonstrate that syndecan-4L is a compact intertwined dimer with a symmetric clamp shape in the central variable V region with a root-mean-square deviation between backbone atom coordinates of 0.95 A for residues Leu(186)-Ala(195). The molecular surface of the 4L dimer is highly positively charged. In addition, no intersubunit NOEs in membrane proximal amino acid resides (C1 region) have been observed, demonstrating that the C1 region is mostly unstructured in the syndecan-4L dimer. Interestingly, two parallel strands of 4L form a cavity in the center of the dimeric twist similar to our previously reported 4V structure. The overall topology of the central variable region within the 4L structure is very similar to that of 4V complexed with the phosphatidylinositol 4,5-bisphosphate; however, the intersubunit interaction mode is affected by the presence of C1 and C2 regions. Therefore, we propose that although the 4V region in the full cytoplasmic domain has a tendency for strong peptide--peptide interaction, it may not be enough to overcome the repulsion of the C1 regions of syndecan-4L.

Amino Acid Sequence↗
PubMed2001

Adaptor protein Lad relays PDGF signal to Grb2 in lung cells: a tissue-specific PDGF signal transduction.

Lad was previously identified as an adaptor protein binding to the SH2 domain of Lck (1). Specific detection of Lad mRNA in lung cells, as well as, in T cells led us to investigate the signaling pathways regulating Lad in lung cells. We found that (i) upon PDGF stimulation, Lad expression is induced in lung cells, especially in the bronchial epithelial cells; (ii) Lad is tyrosine phosphorylated upon PDGF stimulation and is associated with PDGF receptor; (iii) upon PDGF stimulation, Grb2 is recruited to Lad in human embryonic lung cells; (iv) overexpression of Lad elevated AP-1 promoter activity by two- to threefold, whereas dominant negative Lad abrogated PDGF-dependent activation of AP-1 promoter. These results provide a novel mechanism of PDGF-dependent signaling, in which Lad acts as an adaptor in a tissue-specific manner, linking PDGF signal to Grb2 and subsequent activation of AP-1.

3T3 Cells↗
PubMed2001

A single trial analysis of hippocampal theta frequency during nonsteady wheel running in rats.

It has been suggested that hippocampal theta rhythm codes some aspects of motor behavior, but previous studies of the correlation between theta frequency and steady whole body locomotion speed using both linear tracks and wheels have provided inconsistent if not contradictory results. Because the relationship between temporal dynamics of theta frequency and non-steady (or dynamic) whole body locomotion speed can help clarify this issue, single trials of hippocampal EEG were analyzed together with nonsteady wheel running speed recorded during rats perform spontaneous normal locomotion in a wheel. Changes in theta frequency within single trials show positive or negative correlation with nonsteady wheel running speed. As the mean running speed increases and the standard deviation of running speed decreases in a single trial, the correlation between temporal dynamics of theta frequency and nonsteady wheel running speed within the single trial tends to be positive. In addition, we found that the amount of deceleration is also related to the polarity of the correlation coefficients.

Animals↗
PubMed2001

Solution structure, backbone dynamics, and stability of a double mutant single-chain monellin. structural origin of sweetness.

Single-chain monellin (SCM), which is an engineered 94-residue polypeptide, has been characterized as being as sweet as native two-chain monellin. Data from gel-filtration high performance liquid chromatography and NMR has proven that SCM exists as a monomer in aqueous solution. In order to determine the structural origin of the taste of sweetness, we engineered several mutant SCM proteins by mutating Glu(2), Asp(7), and Arg(39) residues, which are responsible for sweetness. In this study, we present the solution structure, backbone dynamics, and stability of mutant SCM proteins using circular dichroism, fluorescence, and NMR spectroscopy. Based on the NMR data, a stable alpha-helix and five-stranded antiparallel beta-sheet were identified for double mutant SCM. Strands beta1 and beta2 are connected by a small bulge, and the disruption of the first beta-strand were observed with SCM(DR) comprising residues of Ile(38)-Cys(41). The dynamical and folding characteristics from circular dichroism, fluorescence, and backbone dynamics studies revealed that both wild type and mutant proteins showed distinct dynamical as well as stability differences, suggesting the important role of mutated residues in the sweet taste of SCM. Our results will provide an insight into the structural origin of sweet taste as well as the mutational effect in the stability of the engineered sweet protein SCM.

Arginine↗
PubMed2001

Design considerations for association studies of candidate genes in families.

In genetic epidemiologic studies, investigators often use generalized linear models to evaluate the relationships between a disease trait and covariates, such as one or more candidate genes or an environmental exposure. Recently, attention has turned to study designs that mandate the inclusion of family members in addition to a proband. Standard models for analysis assume independent observations, which is unlikely to be true for family data, and the usual standard errors for the regression parameter estimates may be too large or too small, depending on the distribution of the covariates within and between families. The consequences of familial correlation on the study efficiency can be measured by a design effect that is equivalent to the relative information in a sample of unrelated individuals compared to a sample of families with the same number of individuals. We examine design effects for studies in association, and illustrate how the design effect is influenced by the intra-familial distribution of covariate values such as would be expected for a candidate gene. Typical design effects for a candidate gene range between 1.1 and 2.4, depending on the size of the family and the amount of unexplained familial correlation. These values correspond to a modest 10% increase in the required sample size up to more than doubling the requirements. Design effect values are useful in study design to compare the efficiency of studies that sample families versus independent individuals and to determine sample size requirements that account for familial correlation.

Adolescent↗
PubMed2001

Immunobead RT-PCR versus regular RT-PCR amplification of CEA mRNA in peripheral blood.

PURPOSE: The reverse transcription polymerase chain reaction (RT-PCR) amplification of tumor-specific mRNA has been used for the detection of cancer cells in peripheral blood. More recently, an immunomagnetic isolation and reverse transcription polymerase chain reaction (immunobead RT-PCR) was developed which has reportedly significant advantages over the previous RT-PCR analysis. In our study, we compared these two methods using a model set of peripheral blood containing tumor cells under standardized conditions. MATERIAL AND METHODS: In order to compare the false positive rate, normal peripheral blood samples from five volunteers were analyzed by both methods. A model set of peripheral blood containing tumor cells was established by adding SNUC4 human colon cancer cells to peripheral blood collected from normal volunteers not showing any nonspecific bands upon electrophoresis of the PCR products. RT-PCR amplification of carcinoembryonic antigen (CEA) mRNA was done with total RNA and mRNA prepared from this model sample. In immunobead RT-PCR analysis, mRNA was prepared from the cells isolated with anti-CEA antibody-coated magnetic beads or anti-Ber-EP4 antibody-coated magnetic beads before the RT-PCR analysis. RESULT: The immunobead RT-PCR yielded no non-specific band, while the regular RT-PCR using total RNA did show non-specific band formation in all five samples. When mRNA rather than total RNA was used, nonspecific bands were formed in three of the five samples. Immunobead RT-PCR allowed the detection of 10(1) tumor cells in 1 ml of peripheral blood. The regular RT-PCR analysis had a detection limit of 10(2) tumor cells in 1 ml of peripheral blood. CONCLUSION: The immunobead RT-PCR proved to be more sensitive and specific than the regular RT-PCR at least in our model system.

Antibodies, Monoclonal↗
PubMed2001

New xenicane diterpenoids from the gorgonian Acalycigorgia inermis.

Eight diterpenes and norditerpenes including five new xenicane metabolites (4--8) have been isolated from the gorgonian Acalycigorgia inermis. The structures of these compounds have been determined by combined spectroscopic analysis. The new compounds exhibited significant cytotoxicity against a human leukemia cell-line.

Animals↗
PubMed2001

New lactone-containing metabolites from a marine-derived bacterium of the genus Streptomyces.

Six novel metabolites containing a lactone moiety as a common structural feature, along with the previously described (-)-blastmycinolactol, have been isolated from the cultivation broth of a bacterium of the genus Streptomyces isolated from marine sediment. On the basis of the results of combined spectroscopic analysis, the structures of the new compounds have been determined as butenolides and 3-hydroxy-gamma-butyrolactones.

Antifungal Agents↗
PubMed2001

New triterpenoid saponins from the sponge Erylus nobilis.

Erylosides G--J (1--4), four new triterpenoid saponins, were isolated from the sponge Erylus nobilis collected from Jaeju Island, Korea. On the basis of the results of combined chemical and spectral analyses, the structures of the aglycones were determined to be lanostane-based, modified penasterols. The oligosaccharide portions were composed of one unit each of L-arabinose, D-galactose, and 2-N-acetyl-D-glucosamine (1 and 3) or two units of L-arabinose and one unit of 2-N-acetyl-D-glucosamine (2 and 4). These compounds exhibited moderate cytotoxicty against a human leukemia cell line.

Animals↗
PubMed2001

New steroidal alkaloids from an undescribed sponge of the genus Corticium.

Two new steroidal alkaloids, along with a previously reported one of the plakinamine class, were isolated from the sponge Corticium sp. collected from Guam. The structures of the new compounds were determined by combined spectroscopic methods. These compounds exhibited moderate cytotoxicity and antifungal activity as well as DNA- and RNA-cleaving activities.

Alkaloids↗
PubMed2001

Treatment of vitamin K deficiency in cystic fibrosis: Effectiveness of a daily fat-soluble vitamin combination.

OBJECTIVE: Patients with cystic fibrosis (CF) and pancreatic insufficiency (PI) commonly have vitamin K deficiency, and those with CF-associated liver disease (CFLD) have universal vitamin K deficiency. We evaluated the effectiveness of an oral fat-soluble vitamin combination (ADEKs) to treat patients with vitamin K deficiency. STUDY DESIGN: Patients with PI and CF (mean age, 15 years; range, 0.6 to 46 years) including 6 with advanced CFLD were prospectively enrolled in a study of a fat-soluble vitamin combination taken on a daily basis. None had received vitamin K supplementation for at least 4 months before the study. Fat-soluble vitamin combination supplementation was given for a minimum of 4 months; the mean vitamin K intake was 0.18 mg/d (SD = 0.1, range, 0 to 0.3). The primary outcome was change in plasma PIVKA-II (prothrombin in vitamin K absence). RESULTS: Before supplementation 58 (81%) of 72 patients had abnormal PIVKA-II levels (>2.9 ng/mL). After supplementation 29 (40%) had abnormal PIVKA-II levels (P =.001). All 6 patients with advanced CFLD had abnormal PIVKA-II levels (median, range of 20.8, 5.5 to 55 ng/mL) before treatment, which corrected to normal in 50% (4.1, 2.1 to 65 ng/mL). Four patients, 2 with CFLD, had a prolonged prothrombin time (>13.5 seconds) at both time periods. CONCLUSIONS: An oral fat-soluble vitamin combination with a modest amount of vitamin K can, as a daily supplement, improve the PIVKA-II levels in patients with PI and CF.

Adolescent↗