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Biomedical subjects

H J Shin

Publications and source records attributed to H J Shin.

At least 19 recordsLinked to original sources

The PDZ domain protein PDZK1 interacts with human peptide transporter PEPT2 and enhances its transport activity.

The proton-coupled peptide transporter PEPT2 (SLC15A2) mediates the high-affinity low-capacity transport of small peptides as well as various oral peptide-like drugs in the kidney. In contrast to its well-characterized transport properties, there is less information available on its regulatory mechanism, although the interaction of PEPT2 to the PDZ (PSD-95, DglA, and ZO-1)-domain protein PDZK1 has been preliminarily reported. To examine whether PDZK1 is a physiological partner of PEPT2 in kidneys, we started from a yeast two-hybrid screen of a human kidney cDNA library with the C-terminus of PEPT2 (PEPT2 C-terminus (PEPT2-CT)) as bait. We could identify PDZK1 as one of the positive clones. This interaction requires the PDZ motif of PEPT2-CT detected by a yeast two-hybrid assay, in vitro binding assay and co-immunoprecipitation. The binding affinities of second and third PDZ domains of PDZK1 to PEPT2-CT were measured by surface plasmon resonance. Co-immunoprecipitation using human kidney membrane fraction and localization of PEPT2 in renal apical proximal tubules revealed the physiological meaning of this interaction in kidneys. Furthermore, we clarified the mechanism of enhanced glycylsarcosine (Gly-Sar) transport activity in PEPT2-expressing HEK293 cells after the PDZK1 coexpression. This augmentation was accompanied by a significant increase in the V(max) of Gly-Sar transport via PEPT2 and it was also associated with the increased surface expression level of PEPT2. These results indicate that the PEPT2-PDZK1 interaction thus plays a physiologically important role in both oligopeptide handling as well as peptide-like drug transport in the human kidney.

Biological Transport↗

Phase II study of capecitabine and irinotecan combination chemotherapy in patients with advanced gastric cancer.

The present study was conducted to evaluate the efficacy and safety of a combination regimen of capecitabine plus irinotecan in patients with advanced gastric cancer. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received oral capecitabine 1000 mg m(-2) twice daily from day 1 to 14 and intravenous irinotecan 100 mg m(-2) on days 1 and 8, based on a 3-week cycle. Forty-one patients were enrolled in the current study, among whom 38 were assessable for efficacy and 40 assessable for toxicity. Three complete responses and 16 partial responses were confirmed, giving an overall response rate of 46.3%. At a median follow-up of 269 days, the median time to progression and overall survival were 5.1 and 8.6 months, respectively. Grade 3/4 neutropenia occurred in four patients and grade 3 febrile neutropenia was observed in two patients. Grade 3 diarrhoea and grade 2 hand-foot syndrome occurred in six patients and eight patients, respectively. The combination of capecitabine and irinotecan was found to be well tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as one of first-line treatment options for advanced gastric cancer.

Adenocarcinoma↗

Cavernous haemangioma of the breast.

Vascular tumours of the breast are rare and most can be classified as either angiosarcomas or haemangiomas. Cavernous haemangiomas are the most common form of mammary haemangioma. We describe a case with unilateral whole breast involvement without associated calcifications, studied with mammography, ultrasound and MRI.

Adolescent↗

Spatial chemical inhomogeneity and local electronic structure of Mn-doped Ge ferromagnetic semiconductors.

We have investigated the chemical distributions and the local electronic structure of potential diluted magnetic semiconductor Ge0.94Mn0.06 single crystals using scanning photoelectron microscopy (SPEM), x-ray absorption spectroscopy (XAS), and photoemission spectroscopy (PES). The SPEM image shows the stripe-shaped microstructures, which arise from the chemical phase separation between the Mn-rich and Mn-depleted phases. The Mn 2p XAS shows that the Mn ions in the Mn-rich region are in the divalent high-spin Mn2+ states but that they do not form metallic Mn clusters. The Mn 3d PES spectrum exhibits a peak centered at approximately 4 eV below E(F) and the negligible spectral weight near E(F). This study suggests that the observed ferromagnetism in Ge1-xMnx arises from the phase-separated Mn-rich phase.

Journal Article↗

Multisoliton complexes moving on a cnoidal wave background.

We obtain solutions of coupled nonlinear Schrodinger equations which describe multisoliton complexes moving on a cnoidal-wave background. Our method is based on the Darboux transformation, which uses Sym's solution of the associated linear equation. Solutions are presented in a matrix determinant form, matrix elements of which are expressed in terms of Jacobi's elliptic functions. Some characteristics of multisoliton complexes like widths and amplitudes are explicitly calculated.

Journal Article↗

Solutions for solitons in nonlinear optically induced lattices.

We calculate stationary configurations of superposed states "soliton + cnoidal wave lattice" of the vector nonlinear Schrödinger equation, using the Darboux transformation technique. The obtained expressions contain the Jacobi elliptic and theta functions, and are easily manageable. There are five stationary configurations, in which one of the defocusing media is stable, while those of the focusing medium are classified into two weakly unstable and two unstable. The checking of the solutions as well as the construction of their typical shapes is accomplished with the help of symbolic package MATHEMATICA.

Journal Article↗

Systematic construction of multisoliton complexes.

We present a simple but powerful method for constructing multisoliton complexes of the coupled nonlinear Schrödinger equation. Our method is based on the Bäckrund-Darboux transformation. A closed form of the matrix determinant is given for multisoliton complexes, including the case of a nonvanishing background. We explicitly work out the solutions of two-, three-, and four-component coupled nonlinear Schrödinger equations.

Journal Article↗

Pigment-lightening effect of N,N'-dilinoleylcystamine on human melanoma cells.

BACKGROUND: Cystamine and linoleic acid have been reported to reduce melanin synthesis in vitro and in vivo. N,N'-dilinoleylcystamine (DLC) is a compound of cystamine and linoleic acid connected by an ester bond. OBJECTIVES: To investigate the effects of DLC on melanin synthesis using cultured human melanoma cells. METHODS: Levels of total melanin, eumelanin and phaeomelanin, tyrosinase protein and tyrosinase activity in situ were measured in HM3KO melanoma cells. Changes in degree of pigmentation were quantified by image analysis and compared with absorbance values. Tyrosinase from HM3KO cells was used to measure the direct effect of DLC on DOPA and DOPAchrome production. RESULTS: At concentrations of 1.4-14 micromol L-1, DLC reduced the pigmentation of HM3KO melanoma cells but did not affect cell growth. The visual decrease in pigmentation produced by DLC was more dramatic than the decrease in total melanin content as measured by absorbance at 500 nm. DLC treatment decreased eumelanin synthesis and increased phaeomelanin synthesis in HM3KO melanoma cells. An in situ tyrosinase assay showed that DLC inhibited tyrosinase activity, as well as the level of tyrosinase protein. CONCLUSIONS: These results suggest that DLC has pigment-lightening effects on HM3KO melanoma cells, produced by reducing the level of eumelanin while increasing the level of phaeomelanin.

Blotting, Western↗

Interference of magnetic and anisotropic tensor susceptibility reflections in resonant X-ray scattering of GdB4.

Resonant x-ray scattering experiments at the Gd L3 edge show interference between magnetic and anisotropic tensor susceptibility (ATS) reflections in GdB4. Energy profiles obtained from the magnetic and ATS resonances exhibited approximately 10 eV separation between the maximum resonance energies. The findings show that the Gd 5d band experienced hybridization giving rise to a significant split into isotropic lower energy band and distorted upper band states that account for the magnetic and ATS scattering, respectively.

Journal Article↗

Interaction of a soliton with a continuous wave packet.

We analyze the scattering of a soliton from a continuous wave packet of arbitrary shape in a fiber, theoretically as well as numerically. Solitons recover their original shapes and velocities after collisions and the effect of collisions is described by the change of velocities of solitons. The theoretical predictions based on a WKB-type approximation are in a good agreement with numerical results.

Journal Article↗

The variables affecting nuchal skin-fold thickness in mid-trimester.

OBJECTIVES: To find out variables that have an effect on the measured values of nuchal skin-fold thickness (NT) and to formulate a regression equation on the basis of those variables. METHODS: The data on gestational age (GA), cephalic index (CI), presentation (Pr, vertex or breech), and the presence or absence of nuchal cord (NC) were collected prospectively on 548 normal singleton fetuses between 16 and 24 weeks gestation, and independent correlation of those variables with NT was calculated by multiple regression analysis and a regression equation was produced. RESULTS: GA had positive correlation and CI had negative correlation with NT. The nuchal skin-fold was thicker among fetuses with breech presentation rather than those with vertex presentation and increased in the presence of nuchal cord. We calculated the expected NT through these observations: for fetuses presenting vertex, NT = 5.608 + 0.243GA - 0.066CI + NC* and for breech, NT = 2.803 + 0.392GA - 0.066CI + NC*. CONCLUSIONS: This is the first report, which takes GA, CI, Pr, and NC for correlation factors with NT as a whole. These equations and further studies on determining the cutoff values of the nuchal skin-fold thickness may improve the sensitivity and specificity for the detection of Down syndrome and enable to minimize unnecessary invasive procedures such as amniocentesis or cordocentesis.

Adult↗

Successive double high-dose chemotherapy with peripheral blood stem cell rescue collected during a single leukapheresis round in patients with high-risk pediatric solid tumors: a pilot study in a single center.

In total, 18 of 26 double high-dose chemotherapies (HDCT) in pediatric solid tumors were rescued with peripheral blood stem cells collected during a single leukapheresis round (single-harvest group, SHG). In the remaining eight HDCT, additional leukapheresis were necessary after the first HDCT (HDCT1) to rescue the second HDCT (HDCT2) (double-harvest group, DHG). Stem cell collection after HDCT1 was inefficient and delayed in patients who had received prior chemotherapy before HDCT1. The interval between HDCT1 and HDCT2 was shorter in SHG than in DHG (median 62.5 days vs 178.5 days, P-value=0.002). Hematologic recovery in HDCT2 was delayed compared to HDCT1. However, there was no difference in hematologic recovery between SHG and DHG. A high rate of treatment-related mortality (TRM) was recorded during HDCT2, but there was no evidence that the shorter interval caused a higher rate of TRM (P-value=0.454). The probability of disease-free survival at 2 years after HDCT2 in the SHG and DHG were 66.7 and 25.0%, respectively (P-value=0.031). Therefore, to administer the second HDCT earlier in double HDCT, and thus to improve the survival of patients with high-risk solid tumors, the single-harvest approach is recommended rather than the double-harvest approach.

Adolescent↗

Vortex filament motion under the localized induction approximation in terms of Weierstrass elliptic functions.

We study quasiperiodic solutions of the localized induction approximation in terms of the elliptic functions of Weierstrass. They describe the Kida-class motion of a thin vortex filament in an incompressible inviscid fluid. Our solution includes various filament shapes such as the vortex ring, the helicoidal filament, the plane sinusoidal filament, and the Hasimoto type-1 soliton filament.

Journal Article↗

Host cell proteins binding to the encapsidation signal epsilon in hepatitis B virus RNA.

The highly conserved encapsidation signal (epsilon) of hepatitis B viral (HBV) pregenomic RNA has been reported as an essential component for encapsidation and protein priming of HBV polymerase. Here, we report that two HBV epsilon RNA-binding host proteins (80 and 43 kDa) and a copurifying protein (100 kDa) were purified and characterized by the combined methods of UV cross-linking analysis with the epsilon RNA and column chromatography. Amino-terminal microsequencing showed that 80- and 43-kDa proteins were identified as the heterodimeric nuclear factor of activated T cells (NF90/NF45) and 100 kDa as a molecular chaperone, the GRP94. The heterodimeric factor interacted preferentially with the upper-bulge region of HBV epsilon RNA helping the HBV polymerase bind the lower-bulge region. Using in vitro protein priming analysis, the initial oligonucleotide of the protein-priming product was deduced as 5'-GAAC-3', which is the complementary sequence of both regions of DR1 and epsilon in the pregenomic RNA. Previously, we also proposed that the GRP94 was associated with HBV polymerase in the human liver cell HepG2. These results suggest that the heterodimeric factor plays an important role in the priming activity of HBV polymerase.

Amino Acid Sequence↗

Homodimers of mutant tryptophan synthase alpha-subunits in Escherichia coli.

Tryptophan synthase alpha-subunit from Escherichia coli functionally exists as a heterotetramer of alpha(2)beta(2) with beta-subunit. While wild-type and mutant (F139W, T24M/F139W, and T24L/F139W) alpha-subunits were expressed as a monomer from recombinant plasmids in Escherichia coli, T24A/F139W, T24S/F139W, and T24K/F139W mutant alpha-subunits were abnormally expressed as soluble homodimers in addition to monomers. Monomers of dimer-forming mutant alpha-subunits retain high affinity to beta-subunit, high activity in stimulating catalytic activities of beta-subunit, and nearly intact content of secondary structure, indicating that the global structures of these monomers are identical to that of F139W alpha-subunit. However, fluorescence spectra of Trp139 and ANS binding indicate that significant perturbations occur in the mutant proteins. Interestingly, these defective properties of monomers caused by residue replacement were partially repaired by the dimer formation. As a result, it is suggested that dimers may be formed by domain or loop swapping, and that residue 24 may play important role in maintaining on-pathway of alpha-subunit folding.

Anilino Naphthalenesulfonates↗

Expression of interleukin-1 beta in lipopolysaccharide stimulated monocytes derived from patients with aneurysmal subarachnoid hemorrhage is correlated with cerebral vasospasm.

Cerebral arterial vasospasm is a frequent complication after aneurysmal subarachnoid hemorrhage (SAH). Immunological activation may affect the development of vasospasm. This study measured the cytokines released from lipopolysaccharide-stimulated monocytes of SAH patients. We measured cerebral artery diameters before and after surgery for SAH. The activation index of interleukin-1 beta (IL-1 beta), but not tumor necrosis factor-alpha (TNF-alpha), was higher in patients with symptomatic vasospasm (5.6+/-1.7; n=11) than in patients without (1.8+/-0.4; n=11) (P=0.039). Furthermore, the IL-1 beta activation index was correlated with the degree of the postoperative angiographic vasospasm (correlation coefficient=-0.66, P=0.007). Individual variation in systemic immune activation, measured by monocyte-derived IL-1 beta expression levels after stimulation, may be associated with the development of vasospasm after aneurysmal SAH.

Adult↗

Clinical significance of molecular genetic changes in sporadic invasive pituitary adenomas.

Several molecular and genetic changes have been found in pituitary adenomas. We looked for correlations between these changes and the degree of invasiveness of the tumors. The invasiveness of 11 pituitary adenomas was graded by Hardy classification. We examined the retinoblastoma gene (RB1.20 on chromosome 13q) and the region around the MEN1 locus (chromosome 11q13.1-5) for loss of heterozygosity. Also examined are p53 mutations using single strain conformation polymorphism, p53 protein overexpression using immuno cytochemistry, homozygous deletions of p15 and p16 by polymerase chain reaction, and cellular proliferative activity using MIB-1 antibody. Six tumors (54.5%) had an LOH at either RB1.20 or the MEN1 locus. LOHs were found more frequently in Grade 4 and stage E tumors (72% and 67%) than in Grade 3 and stage D tumors (25% and 40%). However, no mutation or overexpression of p53 was found. No homozygous deletions of p15 or p16 were identified. The cell proliferative index ranged from 0 to 3%. LOH at 11q13 and 13q may be valuable in predicting the invasiveness of pituitary adenomas.

Adenoma↗

Molecular cloning and cultivar specific expression of MAP kinases from Capsicum annuum.

Two MAP kinases, MK1 and MK2, were cloned from Capsicum annuum (pepper) cv. Subicho using a parsley MAP kinase gene as a heterologous probe. MK1 and MK2 encode stress-inducible protein kinases that can contribute to the response to wounding, UV-C, and cold. MK1 has a 92% amino acid identity with WIPK of tobacco. It was transcriptionally induced in response to wounding. In contrast, no detectable MK1 transcript was found in unwounded leaves of pepper. MK2 has a high level of amino acid homology to MAP kinases, such as NTF4 and SIPK and was constitutively expressed in all tissues. Both MK transcripts were downregulated by UV-C treatment. Each MK protein activation was independently wound-inducible in a cultivar dependent manner. MK1 is phosphorylated in cv. Pungchon but not cv. Subicho; whereas, the MK2 protein activation by wounding is restricted to cv. Subicho. In addition, de novo synthesis of the MK1 protein and tyrosine phosphorylation was rapidly and transiently induced in cv. Pungchon by wounding. In contrast, it is highly unlikely that the MK1 protein is produced in cv. Subicho, even though there is an abundant expression of MK1 mRNA after wounding in this cultivar. In Escherichia coli, which overexpresses MK1, autophosphorylation is observed at conserved threonine and tyrosine phosphorylation sites.

Amino Acid Sequence↗