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Biomedical subjects

G J Cho

Publications and source records attributed to G J Cho.

At least 19 recordsLinked to original sources

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↗

Expression of 14-3-3 zeta and interaction with protein kinase C in the rat retina in early diabetes.

AIMS/HYPOTHESIS: The present study aimed to investigate the expression levels of and the relationship between 14-3-3 zeta and protein kinase C (PKC) in the retina of early diabetes. METHODS: Changes in the expression levels of, and interaction between, 14-3-3 zeta and PKC were investigated by Northern and Western blot analyses, immunoprecipitation and double immunostaining in the retina of diabetic rats after 6 weeks of diabetes. PKC activity was examined using a PKC assay. RESULTS: In the diabetic retina, the molecular levels of 14-3-3 zeta were reduced, while those of PKC beta and zeta were increased. Direct interaction between 14-3-3 zeta and PKC was markedly decreased in the retina after 6 weeks of diabetes, while PKC activity was increased. CONCLUSIONS/INTERPRETATION: These findings show that a reduction in 14-3-3 zeta can induce PKC activation, suggesting that this is a main cause of visual dysfunction in the retina during diabetes.

14-3-3 Proteins↗

Ethanol decreases the expression of mitochondrial cytochrome c oxidase mRNA in the rat.

To evaluate the molecular and cellular bases of effects of ethanol on the brain, we utilized a differential display-polymerase chain reaction. Several cDNA fragments were differentially expressed in the hippocampus of control vs. ethanol-treated rats. One of these genes was homologous to the rat mitochondrial cytochrome c oxidase mRNA. Northern blot analysis revealed that the expression of this message in the whole hippocampus was clearly lower after ethanol treatment. Using in situ hybridization, we also found that cytochrome c oxidase mRNA expression, especially in the CA1 and CA3 of the hippocampal regions, was significantly decreased by ethanol treatment. As cytochrome c oxidase is related to oxidative stress, the present study suggests that ethanol might affect the brain through modulation of an oxidative stress reaction.

Animals↗

TTF-1, a homeodomain gene required for diencephalic morphogenesis, is postnatally expressed in the neuroendocrine brain in a developmentally regulated and cell-specific fashion.

TTF-1 is a member of the Nkx family of homeodomain genes required for morphogenesis of the hypothalamus. Whether TTF-1, or other Nkx genes, contributes to regulating differentiated hypothalamic functions is not known. We now report that postnatal hypothalamic TTF-1 expression is developmentally regulated and associated with the neuroendocrine process of female sexual development. Lesions of the hypothalamus that cause sexual precocity transiently activate neuronal TTF-1 expression near the lesion site. In intact animals, hypothalamic TTF-1 mRNA content also increases transiently, preceding the initiation of puberty. Postnatal expression of the TTF-1 gene was limited to subsets of hypothalamic neurons, including LHRH neurons, which control sexual maturation, and preproenkephalinergic neurons of the lateroventromedial nucleus of the basal hypothalamus, which restrain sexual maturation and facilitate reproductive behavior. TTF-1 mRNA was also detected in astrocytes of the median eminence and ependymal/subependymal cells of the third ventricle, where it colocalized with erbB-2, a receptor involved in facilitating sexual development. TTF-1 binds to and transactivates the erbB-2 and LHRH promoters, but represses transcription of the preproenkephalin gene. The singular increase in hypothalamic TTF-1 gene expression that precedes the initiation of puberty, its highly specific pattern of cellular expression, and its transcriptional actions on genes directly involved in neuroendocrine reproductive regulation suggest that TTF-1 may represent one of the controlling factors that set in motion early events underlying the central activation of mammalian puberty.

Aging↗

Long-term intake of Korean red ginseng in HIV-1-infected patients: development of resistance mutation to zidovudine is delayed.

We have observed that CD4+ T cell counts in human immunodeficiency virus (HIV)-1-infected patients treated with only Korean red ginseng (KRG) are maintained or even increased for a prolonged period. In the present study, we investigated whether the development of resistance mutations in reverse transcriptase (RT) to zidovudine (ZDV) is delayed by combined therapy with KRG and ZDV. Nested polymerase chain reaction (PCR) and direct sequencing methods were used to define RT codons 41, 67, 70, 210, 215 and 219 of the HIV-1 pol gene in DNA from peripheral blood mononuclear cells (PBMC) samples from 18 patients. Nine of these eighteen patients were in the KRG group and had been treated with KRG for 60 +/- 15 months (range: 38-82) and ZDV, and nine were in the control group and had been treated with ZDV only. The patients in the KRG group had been treated with ZDV for 75 +/- 24 months, and CD4+ T cell counts were maintained from 239 +/- 85 to 234 +/- 187 microliters-1 (P > 0.05) during the study period, whereas the patients in the control group had been treated with ZDV for 51 +/- 31 months, and their CD4+ T cell counts decreased from 272 +/- 97 to 146 +/- 154 microliters-1 (P < 0.01). In samples within 24 months of ZDV therapy, the overall incidence of 6 resistance mutations to ZDV was 4.2% and 47% in the KRG and control group (P < 0.01), respectively. In samples after 24 months of therapy, the incidence was 21.7% and 56.3% in the KRG and control group (P < 0.01), respectively. These data suggest that the maintenance of CD4+ T cell counts by ZDV and KRG-intake for a prolonged period might be indirectly associated with delayed development of resistance to ZDV by KRG-intake.

Adult↗

Identification of ligands and coligands for the ecdysone-regulated gene switch.

The ecdysone-inducible gene switch is a useful tool for modulating gene expression in mammalian cells and transgenic animals. We have identified inducers derived from plants as well as certain classes of insecticides that increase the versatility of this gene regulation system. Phytoecdysteroids share the favorable kinetics of steroids, but are inert in mammals. The gene regulation properties of one of these ecdysteroids have been examined in cell culture and in newly developed strains of ecdysone-system transgenic mice. Ponasterone A is a potent regulator of gene expression in cells and transgenic animals, enabling reporter genes to be turned on and off rapidly. A number of nonsteroidal insecticides have been identified that also activate the ecdysone system. Because the gene-controlling properties of the ecdysone switch are based on a heterodimer composed of a modified ecdysone receptor (VgEcR) and the retinoid X receptor (RXR), we have tested the effect of RXR ligands on the VgEcR/RXR complex. Used alone, RXR ligands display no activity on the ecdysone switch. However, when used in combination with a VgEcR ligand, RXR ligands dramatically enhance the absolute levels of induction. This property of the heterodimer has allowed the development of superinducer combinations that increase the dynamic range of the system.

Animals↗

Expression of pituitary adenylate cyclase activating polypeptide (PACAP) and PACAP type I A receptor mRNAs in granulosa cells of preovulatory follicles of the rat ovary.

Pituitary adenylate cyclase activating polypeptide (PACAP) was isolated from ovine hypothalamus and known to stimulate the production of cAMP in anterior pituitary cells. In the recent report, the expression of PACAP was detected in preovulatory follicles, and treatment with PACAP stimulated the production of progesterone and prostaglandin E(2) through the action of AC and PLC pathways in the ovary. PACAP binds to three type receptors. Type I A receptor is coupled to adenylate cyclase (AC) and phospholipase C (PLC) pathways, while type I B and type II receptors are only coupled to AC. Thus, the present study aimed to evaluate the temporal expression of PACAP and its type I A receptor mRNAs in the rat ovary after treatment with pregnant mare's serum gonadotropin and human chorionic gonadotropin (hCG). Northern blot analysis showed that PACAP transcripts were transiently expressed from 3-9 hr after hCG treatment, reaching a maximum at 6 hr. During these time points, PACAP mRNAs were specifically and strongly expressed in granulosa cells and cumulus cells of large preovulatory follicles and interstitial glandular cells. Type I A receptor mRNAs were also transiently expressed in granulosa cells of large preovulatory follicles from 3-9 hr after hCG treatment. PACAP and its type I A receptor mRNAs were expressed in the same preovulatory follicles. These results demonstrate that PACAP acts as an autoregulator or pararegulator through type I A receptor in granulosa cells and cumulus cells of large preovulatory follicles. Thus, we suggest that PACAP may have a critical role in granulosa cells of preovulatory follicles for the preparation of ovulation.

Animals↗

Focus on muscle in orthopedic MRI.

Although much has been learned regarding the pathophysiology and imaging characteristics of orthopaedic muscle injuries, more is unknown and areas of controversy still exist. Consequently, there are two main goals of this article. The first is to address what is known regarding magnetic resonance imaging (MRI) of orthopedic muscle disorders, focusing on selected entities rather than an exhaustive review of the subject. The second is to address areas of current controversy. Our hope is that the discussion that follows will stimulate further interest and investigation.

Diagnosis, Differential↗

Localization of dopamine D1 and D2 receptor mRNAs in the rat systemic and pulmonary vasculatures.

The present study was designed to evaluate the expression of dopamine D1 and D2 receptor mRNAs in systemic and pulmonary vasculatures. Using specific antisense riboprobes for dopamine D1 and D2 receptor cDNAs, in situ hybridization histochemistry was performed in the aorta, common carotid artery, vertebral artery, pulmonary artery, and superior vena cava of the adult male Sprague Dawley rat. In the case of the aorta, common carotid artery, and vertebral artery, dopamine D1 receptor mRNAs localized mainly in the smooth muscle cells of the tunica media. However, the signals of dopamine D2 receptor mRNAs were found in the endothelium and subendothelial layer of tunica intima, and interstitial cells of tunica adventitia. In the case of the pulmonary artery, signals of dopamine D1 receptor mRNAs were detected within the tunica intima, media, and adventitia. Expression of D2 receptor mRNAs was detected in the walls of small blood vessels within the tunica adventitia of the pulmonary artery. There were no detectable signals of dopamine D1 and D2 receptor mRNAs in the vein. The uneven distribution of dopamine D1 and D2 receptor mRNAs in the rat systemic vasculatures and pulmonary artery suggests that dopamine differentially regulates the vasodilation of the systemic and pulmonary arteries through the differential stimulation of dopamine D1 and D2 receptor.

Animals↗

Gluteus medius tendon tears and avulsive injuries in elderly women: imaging findings in six patients.

OBJECTIVE: The purpose of this study is to describe the imaging findings of tears and avulsive injuries of the gluteus medius tendon in elderly women and to evaluate the importance of diagnosis and the implications of treatment in the realm of lateral hip pain. CONCLUSION: Elderly women are susceptible to a spectrum of gluteal tendon abnormalities of the hip, notably tears and avulsive injuries of the gluteus medius tendon, that can be a cause of lateral hip pain and may be underdiagnosed or misdiagnosed. The MR imaging findings of this entity are instrumental in establishing the correct diagnosis in the setting of lateral hip pain and initiating appropriate treatment.

Aged↗

Expression of gonadotropin-releasing hormone (GnRH) and GnRH receptor mRNA in prostate cancer cells and effect of GnRH on the proliferation of prostate cancer cells.

The purpose of this study was to determine the production of gonadotropin-releasing hormone (GnRH), the co-occurrence of GnRH receptors in prostate cancer cells, and the effect of GnRH on prostate cancer cell proliferation. Four human prostate cancer cell lines were studied. LNCaP is an androgen sensitive prostate cancer cell line, DU-145 and PC-3 are androgen resistant, and TSU-Pr1 is uncharacterized. The expression of GnRH and GnRH receptor mRNAs were assessed by in situ hybridization and the effect of exogenous GnRH on proliferation of prostate cancer cells was measured by thymidine incorporation assay. GnRH mRNA expression, determined by in situ hybridization, was found in 83.48% of the LNCaP, 89.7% of the TSU-Pr1, 86.2% of the PC-3 and 95.3% of the DU-145. Signals of GnRH receptor mRNA were detected in more than 95% of the cells of all four cell lines. The proliferation of the prostate cancer cells grown in media supplemented with peptide hormone lacking charcoal-stripped serum was significantly (P < 0.05) suppressed. No significant effect of GnRH on the proliferation of all four prostate cancer cells was observed. In summary, prostate cancer cells produced GnRH and its receptors, and exogenous GnRH treatment did not affect the prostate cancer cell proliferation. The existence of GnRH and GnRH receptor mRNA in the same cell suggests that the role of GnRH produced by prostate cancer cells would be autocrine.

Cell Division↗

Colocalization of dopamine D1 and D2 receptor mRNAs in rat placenta.

Dopamine is present in the human placenta. The major function of dopamine is the inhibition of human placental lactogen (hPL) release from human trophoblastic cells. This effect is mediated by cAMP through dopamine D2 receptors. However, studies on the effects of cAMP in the control of hPL release have yielded conflicting results. The purpose of this study is to explore the distribution of dopamine receptors in the rat placenta. Dopamine D1 and D2 receptor mRNAs were colocalized in the rat placenta by in situ hybridization histochemistry using radiolabeled cRNA probes. Dopamine D1 and D2 receptor mRNAs were detected in large cells of the endometrium of the uterus on day 10 of gestation. On days 12-16 of gestation, hybridization signals were localized mainly in the spongiotrophoblast and giant cells of the junctional zone of the placenta. With the development of the placenta, signals were moving from the junctional zone to the labyrinth zone. Pit-1 mRNA was detected in the placental lactotrophs and was also colocalized in neighboring placental sections. Our results clearly showed that dopamine D1 and D2 receptor mRNAs were coexpressed in the placental lactotrophs that express Pit-1 mRNA.

Animals↗

Comparison of speech recognition ability with different speech processing strategies by Korean cochlear implantees.

Many variables affect the audiologic performance of cochlear implantees. With current methods of evaluation, it is difficult to directly compare auditory function with different speech coding strategies. We compared the audiologic performance directly with F0F1F2 and multipeak speech coding strategies in the same implanted ear of eight Korean cochlear implantees. We tested word and phoneme recognition abilities using Korean word lists for speech audiometry and two-syllable nonsense words, respectively. With the multipeak coding strategy, a significant difference in discrimination ability was found in the initial fricative consonant phonemes (/s/,/ss/,/h/). Our results suggest that the improvement of speech recognition ability with the multipeak coding strategy comes primarily from the better understanding of the initial fricative consonants.

Adult↗

Isolation and properties of heat-labile enterotoxin(s) from enterotoxigenic Escherichia coli.

Various techniques have been applied to the detection of skin reactivity associated with heat-labile Escherichia coli enterotoxin in fermenter-grown cultures of enterotoxigenic strains in syncase medium and in trypticase soy broth. Isolated products that were homogeneous, as determined by disc electrophoresis and sodium dodecyl sulfate gel electrophoresis, differed immunologically and in physicochemical characteristics depending on the strain and medium used, even though the products had similar specific activities in skin tests and in Chinese hamster ovary cells. In support of observations on porcine E.coli enterotoxin, and in contrast to the enterotoxin of Vibrio cholerae, the products were single polypeptide chains with molecular weights ranging from approximately 35,000 ot over 100,000 daltons. Proteolytic cleavage during culture and purification might account for some of the variations observed. The isolated products were almost 10(6)-fold less active than purified choleragen in causing morphologic alterations of Chinese hamster ovary cells, approximately 1,000-fold less active in skin tests, and at least 100-fold less active in rabbit ileal loops. In addition, only 1/100 as much active protein was produced by the strains employed as by V. cholerae. It is possible that accessory or host-derived factors are required. The most effective large-scale procedure for isolation from trypticase soy broth culture supernatants was a sequence of concentration by ultrafiltration, judicious (NH4)2SO4 precipitation, gel filtration on Sephadex G-150, and gel filtration on Agarose A5m, from which the E. coli products (like choleragen) are retarded in their elution. Toxin was isolated from an enterotoxigenic strain that caused diarrhea (total volume, 60-liters) for four days in a patient who had visited Mexico.

Animals↗

Production of staphylococcal alpha toxin. II. Glucose repression of toxin formation.

The effect of glucose on alpha toxin production was studied in the Wood 46 strain of Staphylococcus aureus. Optimal toxin production occurred when 0.2% glucose was present in the medium. Omission of glucose gave lower yields of toxin, and concentrations of 0.5% and higher severely depressed toxin formation. Glucose affected the initiation of alpha toxin synthesis in growing cultures. As the glucose concentration increased, the time lag prior to the onset of toxin production also increased, and maximal rates of synthesis were not obtained until essentially all the glucose had been exhausted from the medium. The addition of glucose to toxin-producing cultures caused a temporary, almost complete repression of toxin formation which was not due to pH changes in the culture. The synthesis of most extracellular proteins was not inhibited during the period of repression. After recovery, toxin was produced at rates equal to those of untreated control cultures. The kinetics of toxin repression and the observation that the glucose analogues, 2-deoxy-d-glucose and alpha-methyl-glucoside, as well as other carbon sources, inhibit toxin production suggest that transient repression is responsible for the inhibition of toxin formation. No evidence for a regulatory role of adenosine 3', 5'-cyclc monophosphate in alpha toxin production was obtained.

Amino Acids↗

Production of staphylococcal alpha toxin. I. Relationship between cell growth and toxin formation.

Alpha toxin production and its relationship to cell growth were studied in the Wood 46 strain of Staphylococcus aureus. Toxin first appeared in the culture in the late logarithmic stage, but at least 80% was produced during the subsequent period of slower cell growth. The toxin concentration per unit of cell mass or viable count increased continually throughout the period of toxin production and and at its maximum represented 1.6 to 2.0% of the dry weight of the cells. The possibility that alpha toxin is released as a result of cell lysis was examined by using the appearance of cellular deoxyribonucleic acid in the medium as an indicator of lysis. The results showed that no appreciable amount of lysis occurred during toxin production; at a time when almost maximum amounts of toxin were present in the culture, less than% 4 of the cells had lysed. This finding, together with the observation that less than 0.25% of the total amount of toxin in the culture could be found intracellularly, indicates that alpha toxin is released from intact cells shortly after it is synthesized.

Animals↗