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Biomedical subjects

S Oh

Publications and source records attributed to S Oh.

At least 55 records · Page 3Linked to original sources

An Australasian test of the recent African origin theory using the WLH-50 calvarium.

This analysis investigates the ancestry of a single modern human specimen from Australia, WLH-50 (Thorne et al., in preparation; Webb, 1989). Evaluating its ancestry is important to our understanding of modern human origins in Australasia because the prevailing models of human origins make different predictions for the ancestry of this specimen, and others like it. Some authors believe in the validity of a complete replacement theory and propose that modern humans in Australasia descended solely from earlier modern human populations found in Late Pleistocene Africa and the Levant. These ancestral modern populations are believed to have completely replaced other archaic human populations, including the Ngandong hominids of Indonesia. According to this recent African origin theory, the archaic humans from Indonesia are classified as Homo erectus, a different evolutionary species that could not have contributed to the ancestry of modern Australasians. Therefore this theory of complete replacement makes clear predictions concerning the ancestry of the specimen WLH-50. We tested these predictions using two methods: a discriminant analysis of metric data for three samples that are potential ancestors of WLH-50 (Ngandong, Late Pleistocene Africans, Levant hominids from Skhul and Qafzeh) and a pairwise difference analysis of nonmetric data for individuals within these samples. The results of these procedures provide an unambiguous refutation of a model of complete replacement within this region, and indicate that the Ngandong hominids or a population like them may have contributed significantly to the ancestry of WLH-50. We therefore contend that Ngandong hominids should be classified within the evolutionary species, Homo sapiens. The Multiregional model of human evolution has the expectation that Australasian ancestry is in all three of the potentially ancestral groups and best explains modern Australasian origins.

Animals↗

Effects of acetylbergenin against D -galactosamine-induced hepatotoxicity in rats.

The hepatoprotective effects of acetylbergenin were examined against D -galactosamine (GalN)-induced liver damage in rats, compared with that of bergenin reported previously. Acetylbergenin was synthesized from acetylation of bergenin, isolated from Mallotus japonicus, to increase lipophilic and physiological activities. Acetylbergenin was administered orally once daily for 7 days and then GalN (400 mg kg(-1), i.p.) was injected at 24 h and 96 h after the final administration of acetylbergenin. Acetylbergenin reduced the elevated serum enzyme activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and gamma -glutamyltransferase and the formation of hepatic malondialdehyde induced by GalN. Acetylbergenin also significantly restored towards normalization the decreased levels of glutathione and the decreased activities of glutathione S-transferase and glutathione reductase induced by GalN. Therefore, these results suggest that acetylbergenin has hepatoprotective effects against GalN-induced hepatotoxicity by inhibiting lipid peroxidation and maintaining an adequate level of GSH for the detoxification of xenobiotics as underlying hepatoprotective mechanisms. In addition, lipophilic acetylbergenin showed more activity in the hepatoprotection than that of the much less lipophilic bergenin reported previously.

Analysis of Variance↗

Sclerosing encapsulating peritonitis in pediatric peritoneal dialysis patients.

The aim of this study was to define the incidence and characteristics of sclerosing encapsulating peritonitis (SEP) in pediatric peritoneal dialysis (PD) patients in Japan. A questionnaire was sent to all dialysis units with at least two pediatric PD patients. Among 687 patients registered, 11 cases (1.6%) of SEP were diagnosed. The mean age of patients with SEP at the start of PD was 9.7+/-3.6 years and at SEP diagnosis, 19.1+/-3.8 years. All patients had undergone PD for more than 5 years, and the mean PD duration was 9.6+/-3.3 years. SEP was diagnosed in 6.6% and 12% of patients dialyzed for >5 years and >8 years, respectively. The incidence of peritonitis among patients with SEP was not different from that among the Japanese pediatric registry. All patients had virtually no residual urine volume and 9 had impaired peritoneal ultrafiltration. Peritoneal calcification was the most-frequent radiological finding. Peritoneal biopsy was performed in 7 patients and confirmed sclerotic peritonitis in all. Ten patients transferred to hemodialysis, and only 1 patient underwent surgery. Three patients died. We recommend that patients on PD for more than 5 years who have impaired peritoneal ultrafiltration or peritoneal calcification should be carefully managed as presumptive cases of SEP.

Adolescent↗

Reversal of the gating polarity of gap junctions by negative charge substitutions in the N-terminus of connexin 32.

Intercellular channels formed by connexins (gap junctions) are sensitive to the application of transjunctional voltage (V(j)), to which they gate by the separate actions of their serially arranged hemichannels (Harris, A. L., D. C. Spray, and M. V. L. Bennett. 1981. J. Gen. Physiol. 77:95-117). Single channel studies of both intercellular and conductive hemichannels have demonstrated the existence of two separate gating mechanisms, termed "V(j)-gating" and "loop gating" (Trexler, E. B., M. V. L. Bennett, T. A. Bargiello, and V. K. Verselis. 1996. Proc. Natl. Acad. Sci. U.S.A. 93:5836-5841). In Cx32 hemichannels, V(j)-gating occurs at negative V(j) (Oh, S., J. B. Rubin, M. V. L. Bennett, V. K. Verselis, and T. A. Bargiello. 1999. J. Gen. Physiol. 114:339-364; Oh, S., C. K. Abrams, V. K. Verselis, and T. A. Bargiello. 2000. J. Gen. Physiol. 116:13-31). A negative charge substitution at the second amino acid position in the N-terminus reverses the polarity of V(j)-gating of Cx32 hemichannels (Verselis, V. K., C. S. Ginter, and T. A. Bargiello. 1994. Nature. 368:348-351;. J. Gen. Physiol. 116:13-31). We report that placement of a negative charge at the 5th, 8th, 9th, or 10th position can reverse the polarity of Cx32 hemichannel V(j)-gating. We conclude that the 1st through 10th amino acid residues lie within the transjunctional electric field and within the channel pore, as in this position they could sense changes in V(j) and be largely insensitive to changes in absolute membrane potential (V(m)). Conductive hemichannels formed by Cx32*Cx43E1 containing a negatively charged residue at either the 8th or 10th position display bi-polar V(j)-gating; that is, the open probability of hemichannels formed by these connexins is reduced at both positive and negative potentials and is maximal at intermediate voltages. In contrast, Cx32*Cx43E1 hemichannels with negative charges at either the 2nd or 5th positions are uni-polar, closing only at positive V(j). The simplest interpretation of these data is that the Cx32 hemichannel can adopt at least two different open conformations. The 1st-5th residues are located within the electric field in all open channel conformations, while the 8th and 10th residues lie within the electric field in one conformation and outside the electric field in the other conformation.

Amino Acid Substitution↗

Mutations in connexin 32: the molecular and biophysical bases for the X-linked form of Charcot-Marie-Tooth disease.

The connexins are a family of homologous integral membrane proteins that form channels that provide a low resistance pathway for the transmission of electrical signals and the diffusion of small ions and non-electrolytes between coupled cells. Individuals carrying mutations in the gene encoding connexin 32 (Cx32), a gap junction protein expressed in the paranodal loops and Schmidt-Lantermann incisures of myelinating Schwann cells, develop a peripheral neuropathy - the X-linked form of Charcot-Marie-Tooth disease (CMTX). Over 160 different mutations in Cx32 associated with CMTX have been identified. Some mutations will lead to complete loss of function with no possibility of expression of functional channels. Some mutations in Cx32 lead to the abnormal accumulation of Cx32 proteins in the cytoplasm, particularly in the Golgi apparatus; CMTX may arise due to incorrect trafficking of Cx32 or to interference with trafficking of other proteins. On the other hand, many mutant forms of Cx32 can form functional channels. Some functional mutants have conductance voltage relationships that are disrupted to a degree which would lead to a substantial reduction in the available gap junction mediated communication pathway. Others have essentially normal steady-state g-V relations. In one of these cases (Ser26Leu), the only change introduced by the mutation is a reduction in the pore diameter from 7 A for the wild-type channel to less than 3 A for Ser26Leu. This reduction in pore diameter may restrict the passage of important signaling molecules. These findings suggest that in some, if not all cases of CMTX, loss of function of normal Cx32 is sufficient to cause CMTX.

Charcot-Marie-Tooth Disease↗

Hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, on carbon tetrachloride-intoxicated rats.

The hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, were evaluated against carbon tetrachloride (CCl(4))-induced liver damage in rats. Bergenin at a dose of 50, 100 or 200 mg/kg was administered orally once daily for successive 7 days and then a mixture of 0.5 ml/kg (ip) of CCl(4) in olive oil (1:1) was injected two times each at 12 and 36 h after the final administration of bergenin. The substantially elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and gamma-glutamyltransferase due to CCl(4) treatment were dose dependently restored towards normalization. Meanwhile, the decreased activities of glutathione S-transferase and glutathione reductase were restored towards normalization. In addition, bergenin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl(4)-intoxicated rats in a dose dependent fashion. The results of this study clearly indicate that bergenin has a potent hepatoprotective action against CCl(4)-induced hepatic damage in rats.

Animals↗

Syntheses and biological evaluation of (18)F-labeled 3-(1-benzyl-piperidin-4-yl)-1-(1-methyl-1H-indol-3-yl)propan-1-ones for in vivo mapping of acetylcholinesterase.

We synthesized novel (18)F-labeled acetylcholinesterase (AChE) inhibitors, 3-[1-(3- and 4-[(18)F]fluoromethylbenzyl)piperidin-4-yl]-1-(1-methyl-1H-i ndol-3-yl )propan-1-ones ([(18)F]1 and [(18)F]2) and 3-[1-(4-[(18)F]fluorobenzyl)piperidin-4-yl]-1-(1-methyl-1H-i ndol-3-yl )propan-1-one ([(18)F]3) in high yields (decay-corrected, 25%-40%) and with high effective specific activities (>37 GBq/micromol). Tissue distribution studies of the [(18)F]1 and the [(18)F]3 in mice showed the nonspecific bindings in brain regions, with metabolic defluorination of the [(18)F]1. The result suggests that these radioligands may not be suitable agents for in vivo mapping of AChE, despite their potent in vitro anti-AChE activities.

Acetylcholinesterase↗

FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH.

We report that the chromatin-specific transcription elongation factor FACT functions in conjunction with the RNA polymerase II CTD kinase P-TEFb to alleviate transcription inhibition by DSIF (DRB sensitivity-inducing factor) and NELF (negative elongation factor). We find that the kinase activity of TFIIH is dispensable for this activity, demonstrating that TFIIH-mediated CTD phosphorylation is not involved in the regulation of FACT and DSIF/NELF activities. Thus, we propose a novel transcriptional regulatory network in which DSIF/NELF inhibition of transcription is prevented by P-TEFb in cooperation with FACT. This study uncovers a novel role for FACT in the regulation of transcription on naked DNA that is independent of its activities on chromatin templates. In addition, this study reveals functional differences between P-TEFb and TFIIH in the regulation of transcription.

DNA-Binding Proteins↗

Bioactive 12-oleanene triterpene and secotriterpene acids from Maytenus undata.

The aerial parts of Maytenus undata yielded four new 12-oleanene and 3,4-seco-12-oleanene triterpene acids, namely, 3-oxo-11alpha-methoxyolean-12-ene-30-oic acid (1), 3-oxo-11alpha-hydroxyolean-12-ene-30-oic acid (2), 3-oxo-olean-9(11), 12-diene-30-oic acid (3), and 3,4-seco-olean-4(23),12-diene-3, 29-dioic acid (20-epi-koetjapic acid) (5), together with the known 3, 11-dioxoolean-12-ene-30-oic acid (3-oxo-18beta-glycyrrhetinic acid) (4), koetjapic acid (6), and the 12-oleanene artifact 3-oxo-11alpha-ethoxyolean-12-ene-30-oic acid (7). Koetjapic acid (6) inhibited the growth of Staphylococcus aureus, methicillin-resistant S. aureus, and Pseudomonas aeruginosa, with an MIC range of 3.125-6.25 microg/mL. The new 3,4-secotriterpene acid 20-epi-koetjapic acid (5) potently inhibited rat neonatal brain microglia phorbol ester-stimulated thromboxane B(2) (IC(50) = 0.5 microM) and superoxide anion (IC(50) = 1.9 microM) generation.

Anti-Bacterial Agents↗

Ginsenoside Rc and Rg1 differentially modulate NMDA receptor subunit mRNA levels after intracerebroventricular infusion in rats.

We investigated the influence of centrally administered ginsenoside on the regulation of mRNA levels of the family of NMDA receptor subtypes (NR1, NR2A, NR2B, NR2C) by in situ hybridization histochemistry in the rat brain. The ginsenosides Rc and Rg1, the major components of ginseng saponin, differentially modulate NMDA receptor subunit mRNA levels in rat brain following prolonged i.c.v.-infusion. Ginsenosides Rc or Rg1 (10 microg/10 microl/hr for 7 days) was infused through preimplanted cannulae connected to osmotic mini-pumps. The level of NR1 mRNA is significantly increased in temporal cortex, caudate putamen, hippocampus, and granule layer of cerebellum in Rg1-infused rats as compared to control group. The level of NR2A mRNA is elevated in the frontal cortex. In contrast, it was decreased in CAI area of hippocampus in Rg1-infused rats. However, there was no significant change of NR1 and NR2A mRNA levels in Rc-infused rats. The level of NR2B mRNA is elevated in cortex, caudate putamen, and thalamus in both Rc- and Rg-infused rats. In contrast, NR2B level is decreased in CA3 in Rg1-infused rats. The level of NR2C mRNA is increased in the granule layer of cerebellum in only Rg1 but not Rc infused rats. These results show that structure difference of ginsenoside may diversely affect the modulation of expression of NMDA receptor subunit mRNA after infusion into cerebroventricle in rats.

Animals↗

Modulation of NMDA receptor subunit mRNA in butorphanol-tolerant and -withdrawing rats.

The NMDA receptor has been implicated in opioid tolerance and withdrawal. The effects of continuous infusion of butorphanol on the modulation of NMDA receptor subunit NR1, NR2A, NR2B, and NR2C gene expression were investigated by using in situ hybridization technique. Continuous intracerebroventricular (i.c.v.) infusion with butorphanol (26 nmol/microl/h) resulted in significant modulations in the NRI, NR2A, and NR2B mRNA levels. The level of NR1 mRNA was significantly decreased in the cerebral cortex, thalamus, and CA1 area of hippocampus in butorphanol tolerant and withdrawal (7 h after stopping the infusion) rats. The NR2A mRNA was significantly decreased in the CA1 and CA3 of hippocampus in tolerant rats and increased in the cerebral cortex and dentate gyrus in butorphanol withdrawal rats. NR2B subunit mRNA was decreased in the cerebral cortex, caudate putamen, thalamus, CA3 of hippocampus in butorphanol withdrawal rats. No changes of NR1, NR2A, NR2C subunit mRNA in the cerebellar granule cell layer were observed in either butorphanol tolerant or withdrawal rats. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased significantly in all brain regions except in the thalamus and hippocampus, at the 7 hr after stopping the butorphanol infusion. These results suggest that region-specific changes of NMDA receptor subunit mRNA (NR1 and NR2) as well as NMDA receptor binding ([3H]MK-801) are involved in the development of tolerance to and withdrawal from butorphanol.

Animals↗

Mitotic chromosome condensation requires Brn1p, the yeast homologue of Barren.

In vitro studies suggest that the Barren protein may function as an activator of DNA topoisomerase II and/or as a component of the Xenopus condensin complex. To better understand the role of Barren in vivo, we generated conditional alleles of the structural gene for Barren (BRN1) in Saccharomyces cerevisiae. We show that Barren is an essential protein required for chromosome condensation in vivo and that it is likely to function as an intrinsic component of the yeast condensation machinery. Consistent with this view, we show that Barren performs an essential function during a period of the cell cycle when chromosome condensation is established and maintained. In contrast, Barren does not serve as an essential activator of DNA topoisomerase II in vivo. Finally, brn1 mutants display additional phenotypes such as stretched chromosomes, aberrant anaphase spindles, and the accumulation of cells with >2C DNA content, suggesting that Barren function influences multiple aspects of chromosome transmission and dynamics.

Cell Cycle Proteins↗

N-Methyl-D-aspartate receptor antagonists enhance the head-twitch response, a 5-hydroxytryptamine2 receptor-mediated behaviour, in reserpine-treated mice.

In this study, N-methyl-D-aspartate (NMDA)-receptor antagonists enhanced the head-twitch response induced by 5-hydroxytryptamine (5-HT) in reserpine-treated mice. To minimize the risk of any indirect involvement of NMDA-receptor antagonists (D(-)-2-amino-5-phosphonopentanoic acid (AP-5), D(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP), (+)-5-methyl-10,11-dihydroxy-5H-dibenzo-[a,d]-cyclohepten-5,10-imi ne (MK-801), ketamine, dextrorphan and dextromethorphan) with 5-HT neurones, vesicle stores of monoamines, especially 5-HT, were depleted with reserpine. In addition, the enhancement of 5-HT-induced head-twitch response was inhibited by apomorphine and NMDA as well as ritanserin in reserpine-treated mice. These results support our previous conclusion that NMDA receptors play important roles in the glutamatergic modulation of 5-HTergic function at the postsynaptic 5-HT2 receptors in mice.

Adrenergic Uptake Inhibitors↗

Characterization and purification of a bacteriocin produced by a potential probiotic culture, Lactobacillus acidophilus 30SC.

Lactobacillus acidophilus 30SC was tested for its potential as a probiotic culture. The strain exhibited good acid tolerance in an artificial gastric solution as well as bile resistance in media containing 0.3% bile acids. The strain produced a heat-stable antimicrobial compound that was shown to be proteinaceous in nature and, therefore, referred to as a bacteriocin. The bacteriocin was active over a wide pH range and inhibited a number of gram-positive bacteria including Listeria ivanovii and pathogenic strains. The bacteriocin was purified by 50% ammonium sulfate precipitation followed by hydrophobic interaction column chromatography. The SDS-PAGE of the active fractions resulted in a single band with estimated molecular mass of 3.5 kDa. These results demonstrate the potential of L. acidophilus 30SC as a probiotic culture that can be utilized in the manufacturing of dairy foods and dietary supplements.

Bacteriocins↗

Detection of the cholera toxin-binding activity of kappa-casein macropeptide and optimization of its production by the response surface methodology.

The cholera toxin (CT)-binding activity of purified kappa-casein macropeptide (CMP) from bovine kappa-casein was detected. In addition, a statistical model was developed to optimize the production of CMP. CMP was prepared by chymosin hydrolysis of kappa-casein and a subsequent 3% trichloroacetic acid treatment. CMP was further fractionated in an ion-exchange column by FPLC. CT binding activity was eluted at 0.18 M NaCl and was a single 8.9 kDa peptide without tyrosine and arginine residues. The CT binding activity was rapidly lost by a carbohydrase treatment. The conditions for CMP production with chymosin were optimized by using the response surface methodology (RSM). The estimated optimum levels of the factors were as follows: reaction temperature, 38.5 degrees C; pH, 6.44; and time, 35.9 min. A validation experiment was performed in which CMP was prepared under the predicted parameters, and it was ascertained that the estimated optimum conditions gave better production of CMP than any other conditions.

Animals↗

[A case of primary lung cancer complicated with post-operative intractable pulmonary fistula].

The case was a 76-year-old male. After thoracoscopic left upper lobectomy against primary lung cancer with poor risks such as complication of systemic lupus erythematosus (SLE) and pulmonary emphysema, oral steroid treatment, heavy smoker, decreased renal function, the patient was complicated with intractable pulmonary fistula and MRSA pyothorax. Intracavitary administration of albumin preparation and fibrin glue (Beriplast P) was effective against pulmonary fistula though it was not helpful in the pleurodesis which was conducted 7 times. Teicoplanin (Targosid) was effective against MRSA pyothorax and maintained the renal function.

Aged↗

The Wilms' tumor 1 tumor suppressor gene represses transcription of the human telomerase reverse transcriptase gene.

Regulation of the human telomerase reverse transcriptase (hTERT) gene is the primary determinant for telomerase enzyme activity, which is found in tumor cells but is largely absent from normal somatic cells. Recent studies have shown that Myc protein can transcriptionally activate the hTERT gene. However, little is known about the repression mechanism of the hTERT gene and telomerase enzyme. Here, we developed an expression cloning strategy to identify cDNAs whose products can repress hTERT promoter activity in telomerase-positive immortal cells. Using this screen, we isolated the Wilms' tumor 1 suppressor gene (WT1). WT1 can repress hTERT promoter activity in 293 kidney cells. The WT1 binding site on the hTERT promoter was identified by deletional analysis. Alteration of the WT1 binding site markedly derepresses transcription from an isolated hTERT promoter by inhibiting interaction of WT1 with DNA. These specific repression effects of WT1 were not observed in HeLa cells, which express no endogenous WT1. Furthermore, we show that WT1 can repress the endogenous hTERT promoter and telomerase enzyme activities. These results suggest that WT1 may be a transcriptional repressor of the hTERT gene, at least in some specific cells.

DNA-Binding Proteins↗