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Biomedical subjects

S W Oh

Publications and source records attributed to S W Oh.

18 recordsLinked to original sources

Villin-type headpiece domains show a wide range of F-actin-binding affinities.

The villin-type "headpiece" domain is a modular motif found at the extreme C-terminus of larger "core" domains in over 25 cytoskeletal proteins in plants and animals. Although headpiece is classified as an F-actin-binding domain, it has been suggested that some expressed fusion-proteins containing headpiece may lack F-actin-binding in vivo. To determine the intrinsic F-actin affinity of headpiece domains, we quantified the F-actin affinity of seven headpiece domains and three N-terminal truncations, under identical in vitro conditions. The constructs are folded and adopt the native headpiece structure. However, they show a wide range of affinities that can be grouped into high, low, and nonspecific-binding categories. Computer models of the structure and charged surface potential of these headpiece domains suggest features important for high F-actin affinity. We conclude that not all headpiece domains are intrinsically F-actin-binding motifs, and suggest that the surface charge distribution may be an important element for F-actin recognition.

Actins↗

Total knee arthroplasty in neuropathic arthropathy.

We describe the results of total knee arthroplasty (TKA) undertaken for severe, neurosyphilitic Charcot arthropathy in ten patients (19 knees). A cemented condylar, constrained prosthesis was implanted in all but two knees. The mean follow-up was 5.2 years (5 to 6). The mean knee score before operation was 36.5 points (30 to 42) which improved to 76 points (58 to 90) after operation as judged by the Hospital for Special Surgery score. At final follow-up three knees (16%) had aseptic loosening which required salvage by an arthrodesis, six (31%) were functioning poorly and ten (53%) were satisfactory. We conclude that although Charcot arthropathy is not an absolute contraindication to total knee replacement, there is a high incidence of serious complications.

Arthropathy, Neurogenic↗

Electroconvulsive shock increases the phosphorylation of Pyk2 in the rat hippocampus.

Recently we reported the activation MAPKs, MEK, and Rafs by electroconvulsive shock (ECS) in the rat hippocampus. However, the upstream pathways for the activation of Raf-MEK-MAPK cascade after ECS have not been studied yet. Since the proline-rich tyrosine kinase 2 (Pyk2) and Src were reported to be involved in the activation of the MAPKs in neuronal cells, we examined tyrosine phosphorylation and activation of Pyk2 in the rat hippocampus after ECS. ECS transiently increased the phosphorylation of Pyk2 at multiple tyrosine residues (Tyr-402, Tyr-580, and Tyr-881). The phosphorylations reached the peak at 1 min and returned to basal level by 10 min after ECS. At 1 min after ECS, the binding of Pyk2 to Src and Grb2, and of Grb2 to Ras increased. These results suggested that ECS activates Pyk2, which then transmits the signal to MAPK cascade via Src, Grb2, and Ras in the rat hippocampus.

Adaptor Proteins, Signal Transducing↗

Applications of phthalimide photochemistry to macrocyclic polyether, polythioether, and polyamide synthesis.

Irradiation of phthalimides which contain N-linked omega-trimethylsilylmethyl-substituted polyether, polythioether, and polysulfonamide chains results in efficient production of the corresponding macrocyclic polyether, polythioether, and polysulfonamide products. These photocyclization reactions follow sequential single electron transfer (SET)-desilylation pathways. Only in the cases of phthalimides, bearing mixed ether-thioether N-substituents, do these excited-state cyclization reactions proceed with lower degrees of regioselectivity. This is a result of competitive desilylation and alpha-to-sulfur deprotonation reactions of the zwitterionic diradical intermediates formed by initial SET.

Ethers↗

In vivo antitumor efficacy of CW252053, a folate-based thymidylate synthase inhibitor.

Previous studies have demonstrated that CW252053, a quinazoline antifolate, exhibits potent inhibitory activity against thymidylate synthase (TS) as well as cytotoxic activity against tumor cell lines in vitro. In this study, we evaluated the in vivo antitumor efficacy of CW252053 in the mouse tumor model. Female B6D2F1 mice were injected with LY3.7.2C TK-/- (thymidine kinase deficient mouse lymphoma) cells into the gastrocnemius muscle. Then, CW252053 was administered twice daily by intraperitoneal injection for 10 days, and tumor growth was monitored daily by leg diameter measurement. All animals in the vehicle, 5-FU, and low dose (30 mg/kg) CW252053 treated groups died between days 12 and 23 because of the tumor burden. In contrast, dosing with 60 mg/kg of CW252053 produced a cure rate against tumor growth of 37.5% and a survival rate of 50%. Even more significantly, a higher dose of CW252053 (120 mg/kg) elicited both a 100% cure rate and a 100% survival rate at the termination of the study, confirming that this compound has very potent in vivo antitumor activity against tumor growth. During the experimental period of this study no signs of toxicity were observed even at the high CW252053 dosage rate of 120 mg/kg.

Animals↗

An N-methyl-D-aspartate antagonist, MK-801, preferentially reduces electroconvulsive shock-induced phosphorylation of p38 mitogen-activated protein kinase in the rat hippocampus.

Electroconvulsive shock (ECS) activates the mitogen-activated protein kinase (MAPK) family in the rat hippocampus, but the signaling pathways for this activation are not well understood. We investigated whether N-methyl-D-aspartate (NMDA) receptor mediated signaling is involved in the phosphorylation-activation of the MAPK family. The NMDA receptor antagonist, MK-801, dose-dependently reduced ECS-induced phosphorylation of p38 and its upstream kinase MKK6 up to 1 mg/kg. MK-801 also reduced the phosphorylation of ERK1/2 and MEK1, but only at high dosage, 2 mg/kg. Moreover, the reduction in the phosphorylation of p38 and MKK6 was greater than that of ERK1/2 and MEK1. Our results suggest that ECS activates p38 and ERK1/2 partly through an NMDA receptor-mediated signaling system in the rat hippocampus and that NMDA receptor mediated signaling is more responsible for the activation of the MKK6-p38 pathway than the MEK1-ERK pathway.

Animals↗

Membrane cytoskeleton: PIP(2) pulls the strings.

A recent application of optical tweezers has shown that plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)) levels control adhesion of the membrane bilayer to the underlying cytoskeleton, by regulated direct binding of PIP(2) to cytoskeletal proteins and/or indirect effects on cytoskeleton structure.

Animals↗

Detection of genetic alterations in the human gastric cancer cell lines by two-dimensional analysis of genomic DNA.

We examined genomic DNA from each of three human-derived gastric cancer cell lines, using the technique of restriction landmark genomic scanning (RLGS) which allows monitoring of approximately 2, 000 NotI landmarks. The resulting DNA spots from cancer cell DNA were compared with those in normal mucosa or gastric primary tumor. In all, 9 intense spots were detected from two of the three cancer cell lines. Two highly intensified spots were common in the two cancer cell lines and proven to be originated from DNA region containing the human c-myc proto-oncogene on chromosome 8. The degree of amplification of c-myc DNA was similar to each other and was estimated to be 60-fold as compared to those from normal mucosa DNA. On the basis of chromosome-assigned RLGS (CA-RLGS), other spots were assigned to each chromosome, such as one on chromosome 8, two each from chromosome 20, and three on one of chromosome 9-12. The remaining spot seems to be due to demethylation of a repetitive element. Twenty-four spot that were lost due to either homozygous deletion or methylation on corresponding NotI cleavage sites were commonly observed in all cancer cells. These spots were also assigned to each chromosome: one each from chromosome 2, 6, 7, 13, 14, 16, and 20, two each from chromosome 3 and 5, and nine from chromosome 9-12 by CA-RLGS. Many of the multi-copy spots corresponding to ribosomal RNA genes were greatly decreased due mainly to methylation on CpG islands along with minor rDNA variants, indicating that only minor rRNA genes may be silenced in these cancer cells. These results show that the present alterations detected by RLGS might be useful for identification of candidate genes inactivated or expressed unexpectedly in tumor development and tumor progression in the stomach.

Base Sequence↗

Differential activation of c-Jun N-terminal protein kinase and p38 in rat hippocampus and cerebellum after electroconvulsive shock.

Electroconvulsive shock (ECS), an effective treatment for psychiatric diseases, has been reported to induce immediate-early genes (IEGs) and to activate p42 and p44 MAPKs (ERK-1 and ERK-2) in rat brain. In this study, we examined the activation of the other members of MAPK family, c-Jun N-terminal protein kinase (JNK/SAPK) and p38. Following ECS, the phosphorylation of p38 was substantially increased in both hippocampus and cerebellum, but the increase of JNK phosphorylation was observed only in hippocampus. We also investigated the phosphorylation of their upstream kinases, SEK-1, MKK6 and MKK3. In both hippocampus and cerebellum, the phosphorylation of MKK6 showed closer correlation with p38 phosphorylation than that of MKK3. However, SEK-1, known as upstream kinase of JNK and p38 in vitro, corresponded with none of MAPKs. These results, with previous reports on the activation of ERK, indicate that ECS activates three MAPKs differentially in rat hippocampus and cerebellum, and suggest the possibility that unknown MAPKK may be involved in the activation of JNK in rat brain after ECS.

Animals↗

Synthesis of 2',3'-dideoxyisoguanosine from guanosine.

2,3'-Dideoxyisoguanosine was synthesized from guanosine via intermediate 6-[(4-methylphenyl)thio]-2-oxo-9-(2',3',5'-tri-O-acetyl-beta-D-ribofuran osyl)-2,3-dihydropurine (4). The 2-oxo, 6-amino and 5'-hydroxy triprotected isoguanosine derivative was utilized to reduce high polarity and promote poor solubility of intermediates. The protecting groups for oxo and 6-amino were easily removed in reduction of olefin in ribose without additional reaction steps. 2',3'-Vicinal diol in ribose sugar moiety was transformed to olefin with Bu3SnH by radical reaction via bisxanthate. Removing 5'-O-TBDMS protecting group gave final product, 2',3'-dideoxyisoguanosine (12) in a 10% overall yield.

Alkenes↗

A Minnesota multiphasic personality inventory profile of ChunDoSunBup qi-trainees: a preliminary study.

The aim of this study is to explore the effects of ChunDoSunBup Qi-training on personality traits. Twenty-six normal healthy subjects (mean age = 26.58 +/- 6.56) and 26 CDSB Qi-trainees (mean age = 27.74 +/- 5.21) participated in this study. Analysis of MMPI profiles showed that CDSB Qi-trainees scored significantly lower on Depression (D), Hysteria (Hy), Paranoia (Pa), Schizophrenia (Sc) and Frequency (F) and significantly higher on the Correction (K) Scales. In addition, CDSB Qi-trainees reported a significantly lower Cook-Medley Hostility (Ho) scale than that of controls. This preliminary study suggests that CDSB Qi-training may be effective in protection as well as restoration of emotional, psychological symptomatology and personality trait disorder.

Adult↗

Effects of chundosunbup Qi-training on psychological adjustments: a cross-sectional study.

This cross-sectional investigation evaluated the trend of psychological changes by ChunDoSunBup (CDSB) Qi-training using a self-report inventory of emotional distress, Symptom Check List-90-Revision (SCL-90-R). 41 normal healthy subjects (mean age = 20.98 +/- 5.39) and 123 CDSB Qi-trainees (divided into three groups, Q1, Q2 and Q3) participated in this study. Group Q1 has received 1-4 months CDSB Qi-training (age 21.95 +/- 7.82, n = 41); Q2 has 5-12 months Qi-training (age 20.0 +/- 7.75, n = 41); and Q3 has more than 13 months Qi-training (age 22.68 +/- 6.72, n = 41). Our results show that Qi-trainees over 13 months had significantly lower scores compared to controls. A significant negative correlation was found between the Qi-training period and all SCL-90-R subscales except phobic anxiety. These results suggest that CDSB Qi-training is effective in protection as well as reduction of psychological symptomatology.

Adult↗

Spontaneous gastric carcinoid tumors in the striped field mouse (Apodemus agrarius).

Gastric carcinoid tumors were found in seven of 135 striped field mice (Apodemus agrarius) by routine histopathologic examination. All these carcinoids occurred in mature striped field mice aged 72-100 weeks. Six animals were females and only one was male. Only two of seven tumors were detectable by gross examination. Grossly, tumors were located in the fundus of the glandular stomach. All seven tumors were microscopically single in the stomach and two mice exhibited extragastric metastasis. Tumors from all the mice were characterized by densely packed sheets of round to polygonal cells, subdivided into packets by a fine fibrovascular stroma. The cytoplasm of all tumor cells from all the mice contained argyrophil granules when stained by Grimelius and Sevier-Munger silver procedures. All seven mice with gastric carcinoids exhibited positive immunoreactivity to neuron specific enolase. Psammoma bodies, concentrically laminated microcalcification, were characteristic findings in gastric carcinoids from five mice. There were also a concomitant and independent hepatocellular adenoma in one case and hepatocellular carcinoma in two cases. The present cases provide the first description of spontaneous gastric carcinoid tumors in the striped field mice.

Animals↗

Construction of a human full-length cDNA bank.

We aimed to construct a full-length cDNA bank from an entire set of human genes and to analyze the function of a protein encoded by each cDNA. To achieve this purpose, a multifunctional phagemid shuttle vector, pKA1, was constructed for preparing a high-quality cDNA library composed of full-length cDNA clones which can be sequenced and expressed in vitro and in mammalian cells without subcloning the cDNA fragment into other vectors. Using this as a vector primer, we have prepared a prototype of the bank composed of full-length cDNAs encoding 236 human proteins whose amino acid sequences are identical or similar to known proteins. Most cDNAs contain a putative cap site sequence, some of which show a pyrimidine-rich conserved sequence exhibiting polymorphism. It was confirmed that the vector permits efficient in vitro translation, expression in mammalian cells and the preparation of nested deletion mutants.

Animals↗

Schizophrenia and cerebral laterality.

Investigators have suggested that schizophrenic patients have reversals of abnormal structural abnormalities and abnormal left hemisphere function. The authors attempted to know of the pattern of cerebral asymmetry in schizophrenic patients and controls on the computerized tomography scans of thirty right-handed schizophrenic patients and thirty right-handed control subjects. Compared to thirty right-handed controls, the schizophrenic patients had a significantly increased frequency of frontal and occipital reversals. This result suggests that reversals of neuroanatomical asymmetries, and by implicating the abnormalities of lateralization, are relevant to some schizophrenics. Statistics were done by the Chi square method.

Adult↗

Characterization of myosin heavy chain and its gene in Amoeba proteus.

Monoclonal antibodies against the myosin heavy chain of Amoeba proteus were obtained and used to localize myosin inside amoebae and to clone cDNAs encoding myosin. Myosin was found throughout the amoeba cytoplasm but was more concentrated in the ectoplasmic regions as determined by indirect immunofluorescence microscopy. In symbiont-bearing xD amoebae, myosin was also found on the symbiosome membranes, as checked by indirect immunofluorescence microscopy and by immunoelectron microscopy. The open reading frame of a cloned myosin cDNA contained 6,414 nucleotides, coding for a polypeptide of 2,138 amino acids. While the amino-acid sequence of the globular head region of amoeba's myosin had a high degree of similarity with that of myosins from various organisms, the tail region building a coiled-coil structure did not show a significant sequence similarity. There appeared to be at least three different isoforms of myosins in amoebae, with closely related amino acids in the globular head region.

Amino Acid Sequence↗