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Biomedical subjects

J K Cho

Publications and source records attributed to J K Cho.

At least 19 recordsLinked to original sources

Development of bovine oocytes reconstructed with different donor somatic cells with or without serum starvation.

We conducted this study to examine whether serum starvation in culture contributes to better development of bovine reconstructed oocytes and to evaluate which serum-starved somatic cell is the most effective for cloned calf production. In Experiment 1, donor cells of four different types (cumulus cells, ear fibroblasts, oviduct cells and uterine cells) were either serum-starved or not before fusion with enucleated oocytes, and reconstructed oocytes were further cultured for 168 h. Regardless of serum starvation, cumulus cells or ear fibroblasts yielded higher (P < 0.05) rates of fusion than other cells (62.6-69.3 versus 33.3-38.7%). In the serum-starved group, the first cleavage after reconstruction was significantly increased in cumulus cells and ear fibroblasts, compared with oviduct cells (93.4-94.3 versus 78.8-86.0%), and oocytes reconstructed with either of these yielded more blastocysts than oocytes reconstructed with oviduct or uterine cells (40.6-43.8 versus 20.3-19.0%). We observed a similar pattern in the non-starved group, but we found a significant increase in blastocyst formation was found only in cumulus cells compared with other donor cells (42.6 versus 15.4-27.7%). Overall comparison showed that serum starvation increased the rates of cleavage and development to the blastocyst stage, but we found a statistical significance only in the cleavage rate (80.0 versus 89.5%). In Experiment 2, we transferred randomly selected 59 blastocysts that were developed from oocytes reconstructed with serum-starved cells to 44 synchronised recipients. Of those recipients, 23 became pregnant on Day 60 after transfer (52.3%) and 12 (27.3%) delivered cloned calves. The mean gestation length and birth weight was 275 +/- 8 days and 39.6 +/- 15.6 kg, respectively. Although there was no significant difference among donor cells, blastocysts that were derived from oocytes reconstructed with ear fibroblasts yielded the highest rates of pregnancy (50.0%) and delivery (27.3%). In conclusion, serum starvation is effective for improving preimplantation development of oocytes reconstructed with cumulus or ear fibroblast cells and it may positively influence on obtaining better pregnancy outcome.

Animals↗

A prospective correlation of Laurén's histological classification of stomach cancer with clinicopathological findings including DNA flow cytometry.

Between November 1990 and December 1992, 217 patients with stomach cancer were enrolled in a prospective study evaluating the prognostic value of DNA flow cytometry. Laurén's histological type was evaluated in 216 cases, of which 102 (47%) were of the diffuse type, 74 (34%) were of the intestinal type, and 40 (19%) were mixed type tumors. Laurén's histological type showed a significant correlation with age (p = 0.028), sex (p = 0.004), tumor size (p = 0.002), T stage (p = 0.006), overall TNM stage (p = 0.008), histological grade (p < 0.001), and tumor ploidy (p < 0.001). Intestinal type stomach cancer showed a significantly higher proportion of aneuploidy [diffuse vs. intestinal type; 41/102 (40%) vs. 52/74 (70%)]. After a median follow-up of 66.1 months (range, 29.6-78.1), 110 of 216 patients (51%) survived. Patients with intestinal type stomach cancer had a significantly better survival than did those with diffuse type stomach cancer (64% vs. 42% of patients surviving, p = 0.020). Our study suggests that there are biological differences between the two subtypes of Laurén's classification of stomach cancer in addition to the morphological differences. Laurén's classification should remain valid in future studies investigating the pathogenetic and clinical aspects of stomach cancer.

Adult↗

Births of freemartins derived from embryos reconstructed with ear fibroblasts.

Although the combination of artificial insemination (AI) and embryo transfer (ET) is effective for preventing large offspring syndrome in clone cattle production, it may cause freemartinism. In this study, 51 reconstructed embryos were transferred to artificially inseminated recipients. Of those 9 twin pregnancies, three delivered male and female offsprings. The females had tufts of long coarse hair and short blind pouch at the vaginal end. At necropsy, hypoplastic testicles and epididymis, which connected to the uterus through the spermatic cord, were found and seminal vesicles were also noted. All females had mixed sex chromosome configuration (60, XX and 60, XY). These results suggest that the combined ET program can cause freemartinism, which reduces the efficiency of clone cattle production.

Animals↗

Cocaine administration decreases functional connectivity in human primary visual and motor cortex as detected by functional MRI.

Functional magnetic resonance imaging (fMRI) was conducted to observe the effects of cocaine administration on the physiological fluctuations of fMRI signal in two brain regions. Seven long-term cocaine users with an average age of 32 years and 8 years of cocaine use history were recruited for the study. A T2*-weighted fast echo-planar imaging (EPI) pulse sequence was employed at 1.5 T to acquire three sets of brain images for each subject under three conditions (at rest, after saline injection, and after cocaine injection [0.57 mg/kg]). Cross-correlation maps were constructed using the synchronous, low frequency signal from voxel time courses after filtering respiratory, cardiac, and other physiological noise. A quantitative evaluation of the changes in functional connectivity was made using spatial correlation coefficient (SCC) analysis. A marked 50% reduction in SCC values in the region of primary visual cortex and 43% reduction in SCC values in the region of primary motor cortex were observed after cocaine administration. This significant reduction in SCC values in these cortical regions is a reflection of changes in neuronal activity. It is suggested that the observed changes in low frequency components after acute cocaine administration during a resting, no-task situation may be used as a baseline reference source when assessing the effects of cocaine on task-driven activation or on mesolimbic dopamine pathways.

Adolescent↗

Hepatitis C virus infection in cocaine users--a silent epidemic.

Over a recent three year period, approximately 600 individuals responded to newspaper advertisements for research studies requiring healthy, cocaine using subjects. These subjects were screened using a standard phone interview in order to eliminate individuals with known medical or psychiatric illnesses that would exclude them from ongoing neuroimaging studies of drug abuse. Individuals were specifically asked about their hepatitis and HIV status. Of these, 170 subjects passed the phone screen, having no known medical or psychiatric illness outside of cocaine abuse/dependence and were willing to be further evaluated for the studies. These subjects were brought to the Medical College of Wisconsin's General Clinical Research Center and tested for, among other measures, hepatitis B, hepatitis C, and HIV. Of these, 144 completed the examination and all testing. In this cohort of assumed healthy subjects, 47 (33%) tested positive for antibodies to the hepatitis C virus (HCV). Only 7 (5%) tested positive for the hepatitis B surface antigen and 2 (1.4%) to HIV. The demographics of this cohort are 56% African-American, 81% male, 75% never-married, 55% unemployed with a mean age of 36 years. The percentage of subjects reporting any lifetime intravenous drug use among the HCV(+) and the HCV(-) cohorts was 77% vs. 29% respectively. Some routes of HCV transmission are still unclear and may reflect lifestyle or other factors related to cocaine use outside of parenteral drug use. Since almost all HCV infections become chronic, and many progress to chronic active hepatitis, cirrhosis, and ultimately hepatocellular carcinoma, these observations suggest a significant epidemic in an unsuspecting population with little regular access to health care. These individuals also form a large pool for the continued transmission of HCV to the general population. Additional public health interventions are suggested.

Adult↗

Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli.

OBJECTIVE: Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood. METHOD: To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1 ) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity). RESULTS: Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites, just three (anterior cingulate, right inferior parietal lobule, and the caudate/lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film. CONCLUSIONS: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.

Adult↗

Purification of membrane-bound lactoferrin from the human milk fat globule membrane.

Although lactoferrin is known as a basic soluble glycoprotein, the presence of the membrane-bound form of this protein has also been demonstrated in human milk. Membrane-bound lactoferrin was extracted from the human milk fat globule membrane with a detergent mixture of 1% Tween-20, 0.5% C12E8, and 0.5 M KCl in 20 mM Tris-HCl (pH 7.4). Lactoferrin in the detergent-soluble fraction was purified by affinity chromatography with Concanavalin A and by hydrophobic chromatography with phenyl-Superose. The purified protein gave a single band of 80 kDa by SDS-PAGE. Its N-terminal amino acid sequence was consistent with that of human lactoferrin.

Amino Acid Sequence↗

Shared epitope for monoclonal IR162 between Anisakis simplex larvae and Clonorchis sinensis and cross-reactivity between antigens.

IR162 is a rat monoclonal IgE antibody (mAb). In the investigation of rat IgE production, the antigens recognized by IR162 (IR-Ags) were found to be expressed by a variety of helminthic parasites. By western blot analysis, IR162 detected bands in crude extracts of Anisakis simplex larvae, Clonorchis sinensis, Paragonimus westermani, plerocercoids of Spirometra mansoni, and Toxocara canis. Excretory-secretory material from A. simplex larvae also contained a protein recognized by IR162. IR162 mAb obtained from both Serotec and Zymed recognized identical bands of A. simplex larvae. Sandwich enzyme-linked immunosorbent assay analysis indicated that both IR-Ags of A. simplex larvae (IR-As) and C. sinensis (IR-Cs) were important antigens with respect to induction of specific IgG in human infections with these 2 organisms. Even though minimal cross-reaction between IR-As and IR-Cs was observed using sera from infected individuals, these results indicate that IR-Ags are found in the parasites examined, that IR-As and IR-Cs are the antigens that induce specific antibody in natural infection, and that the epitope that binds IR162 is shared by A. simplex larvae and C. sinensis.

Animals↗

1,25 dihydroxyvitamin D3 enhances the calcium response of keratinocytes.

The steroid hormone 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) regulates cell proliferation and differentiation. Intracellular calcium (Cai) concentrations play a crucial role in these events. From our previous studies, we have demonstrated a calcium receptor (CaR) in keratinocytes which appears to regulate the initial release of Cai from intracellular stores in response to extracellular calcium (Cao) and so is likely to participate in the differentiation process. In this study, we determined whether the ability of 1,25(OH)2D3 to enhance Ca++ -induced differentiation was mediated at least in part through changes in the CaR. Keratinocytes were grown in keratinocyte growth medium (KGM) with 0.03 mM, 0.1 mM, or 1.2 mM Ca and treated with 10(-8) M 1,25(OH)2D3 till harvest after 5, 7, 14, and 21 days. CaR mRNA levels were quantitated by polymerase chain reaction. The results were compared to the ability of 1,25(OH)2D3 to enhance calcium-stimulated increases in Cai. In cells grown in 0.03 mM Ca, the CaR mRNA levels decreased with time. 1,25(OH)2D3 stimulated the levels at 5 days and prevented the falloff over the subsequent 16 days. On the other hand, in cells grown in 0.1 or 1.2 mM Ca, the message levels remained high, and 1,25(OH)2D3 had no further effect. To study the functional relationship, we harvested cells after 5 and 7 days in culture following a 24 h treatment with 1,25(OH)2D3 or vehicle to measure the Cai response to 2 mM Cao. The preconfluent cells grown in 0.03 mM Ca showed a nearly twofold increase in the Cai response to Cao when pretreated with 1,25(OH)2D3, whereas the confluent cells and those grown in 1.2 mM Ca showed no enhancement by 1,25(OH)2D3. Studies with 45Ca influx into keratinocytes revealed that 1,25(OH)2D3 enhanced the influx in preconfluent and confluent cells when grown in KGM containing 0.03 mM Ca but not in cells grown in 1.2 mM calcium. We conclude that 1,25(OH)2D3 maintains the CaR mRNA levels in cells grown in 0.03 mM Ca, thus maintaining their responsiveness to Cao and so ensuring their ability to differentiate in response to the calcium signal.

Base Sequence↗

Changes of splenocyte IFN-gamma mRNA synthesis in rats infected with Paragonimus westermani.

Changes in the expression level of splenocyte IFN-gamma mRNA of Sprague-Dawley (SD) rats infected with Paragonimus westermani were analyzed by competitive reverse transcription-polymerase chain reaction (RT-PCR) followed by southern blot. The template RNA was extracted from the splenocytes of rats infected with 20 metacercariae of P. westermani. The products of competitive RT-PCR were subjected to southern blot and enhanced chemiluminescence (ECL), and analyzed with a densitometer. In comparison with that of uninfected control rat splenocytes (value of 1), the levels of mRNA expression of IFN-gamma had changed to 0.747 at 1 week post infection (PI), 0.00175 at 2 week PI, 0.0217 at 3 week PI, 0.194 at 4 week PI and then to 0.537 at 5 week PI. The level at 7 week PI had returned to 1.25, comparable with that of uninfected rats. These results show that, when infected with P. westermani, the levels of IFN-gamma mRNA of SD rat splenocytes were remarkably reduced by more than 500 times at 2 week PI and restored to normal level at 7 week PI.

Animals↗

Nicotine-induced limbic cortical activation in the human brain: a functional MRI study.

OBJECTIVE: Nicotine is a highly addictive substance, and cigarette smoking is a major cause of premature death among humans. Little is known about the neuropharmacology and sites of action of nicotine in the human brain. Such knowledge might help in the development of new behavioral and pharmacological therapies to aid in treating nicotine dependence and to improve smoking cessation success rates. METHOD: Functional magnetic resonance imaging, a real-time imaging technique, was used to determine the acute CNS effects of intravenous nicotine in 16 active cigarette smokers. An injection of saline followed by injections of three doses of nicotine (0.75, 1.50, and 2.25 mg/70 kg of weight) were each administered intravenously over 1-minute periods in an ascending, cumulative-dosing paradigm while whole brain gradient-echo, echo-planar images were acquired every 6 seconds during consecutive 20-minute trials. RESULTS: Nicotine induced a dose-dependent increase in several behavioral parameters, including feelings of "rush" and "high" and drug liking. Nicotine also induced a dose-dependent increase in neuronal activity in a distributed system of brain regions, including the nucleus accumbens, amygdala, cingulate, and frontal lobes. Activation in these structures is consistent with nicotine's behavior-arousing and behavior-reinforcing properties in humans. CONCLUSIONS: The identified brain regions have been previously shown to participate in the reinforcing, mood-elevating, and cognitive properties of other abused drugs such as cocaine, amphetamine, and opiates, suggesting that nicotine acts similarly in the human brain to produce its reinforcing and dependence properties.

Adolescent↗

Decrease of Ca(2+)-ATPase activity in human keratinocytes during calcium-induced differentiation.

Ca2+ regulates keratinocyte differentiation by increasing intracellular Ca2+ levels. Ca(2+)-ATPase in the Ca(2+)-induced differentiation of human keratinocytes was investigated by measuring Ca(2+)-ATPase mRNA, protein, and activity levels. Human keratinocytes were grown in Keratinocyte Growth Medium containing 0.03, 0.1, or 1.2 mM Ca2+ and assayed on days 2, 5, 7, 14, and 21. Ca(2+)-ATPase mRNA levels were found to be modestly increased in 5-, 7-, and 14-day cultured cells as compared with 2-day cultured cells, but levels fell below that of the 2-day cultured cells in the 21-day cultured cells. The Ca(2+)-ATPase mRNA levels were not affected by Ca2+ levels. A 135-kDa protein in human keratinocytes cross reacted with the monoclonal antibody against human erythrocyte Ca(2+)-ATPase. The level of this protein was decreased by Ca2+ and lost during differentiation, in parallel with the loss of enzymatic activity. Ca2+ influx of postconfluent 1.2 mM Ca(2+)-grown cells was higher than that of cells grown in lower Ca2+ concentrations. Ca2+ efflux from postconfluent cells grown in 0.03 mM Ca2+ was less than that from cells grown in stronger Ca2+ concentrations. These results suggest that the loss of the plasma membrane Ca(2+)-ATPase with time in culture contributes to the rise in intracellular Ca2+, thus promoting keratinocyte differentiation.

Ca(2+) Mg(2+)-ATPase↗

Paget bone disease involving young adults in 3 generations of a Korean family.

Although the etiology of Paget bone disease (PBD) is unknown, increasing evidence implicates a "slow virus" infection of the skeleton, perhaps in genetically predisposed individuals. PBD is rare in Asia. We describe a Korean family with PBD. The propositus noticed bowed limbs at approximately 25 years of age. Radiologic studies made when he was 55 years old revealed essentially panostotic PBD. Serum alkaline phosphatase (ALP) activity and osteocalcin (OC) levels were markedly elevated. An iliac crest specimen showed classic histopathologic changes of PBD. Additionally, palpable swellings were first observed at age 45 years at his occiput, pubic ramus, ileum, and facial bones. They contained numerous multinucleated cells and were originally diagnosed as giant cell tumors. However, we found that, like osteoclasts, these cells expressed considerable tartrate-resistant acid phosphatase activity. These "extraskeletal osteoclastomas" resolved rapidly with dexamethasone treatment. Two daughters, 20- and 24-years-of-age, were discovered by study of his 5 children to have elevated serum ALP activity and OC levels and widespread PBD. Both women, however, are without palpable masses and are asymptomatic. The propositus' father, who died at age 55 years, had similar skeletal deformities beginning at age 20 years, but was not examined. Leukocytopenia was found in the 3 living family members with PBD. There was no evidence for linkage of the PBD to HLA loci. The condition appears to be transmitted as an autosomal dominant trait and is manifest in young adult life. Multicentric extraskeletal osteoclastomas with remarkable sensitivity to dexamethasone treatment appear to be another unusual feature of this family's disorder. In this family, the stimulus for PBD is so great that the PBD is apparent at an early age, affects essentially the entire skeleton, and leads to the formation or extension of osteoclast-like cells into nonosseous tissues (extraskeletal osteoclastomas). This 3-generation kindred in Korea, where PBD is rare, shows a strong clustering of PBD compatible with autosomal dominant inheritance. Leukocytopenia appears to distinguish affected family members, but any role for this abnormality in the pathogenesis of PBD is unclear. Our findings support a heritable diathesis for PBD, perhaps mediated by an immune deficiency.

Adult↗

Synthesis and antibacterial activity of 1-beta-methylcarbapenem having a 1,3-diazabicyclo[3.3.0]octan-4-one moiety.

The synthesis of new series of 1-beta-methylcarbapenems having a 1,3-diazabicyclo[3,3,0]octan-4-one moiety is described. Their in vitro antibacterial activities against both Gram-positive and Gram negative bacteria are reported and the effect of the substituent on the bicyclic ring was investigated and was in agreement with findings from our previous studies.

Anti-Bacterial Agents↗

Dissociation and complexation of fluoroquinolone analogues.

The dissociation and the complexation behaviours of four fluoroquinolone antibiotics have been studied. The acid dissociation constants of ciprofloxacin, enoxacin, norfloxacin and ofloxacin were determined by conventional potentiometric and conductometric techniques. Increasing the Hammett substituent constant, the pKa values were decreased. The absorption of fluoroquinolones in the intestinal tract are probably transported by pH-dependent mechanisms. Formation constants of the iron(III) complexes (1:1) of the fluoroquinolone analogues were determined by spectrophotometry. The optimum pH for complexation was 3.80.

Anti-Infective Agents↗

Early gastric cancer in Korea.

We reviewed the 639 cases of early gastric cancer from nation-wide 16 medical centers. The proportion of early gastric cancer among surgically resected gastric carcinoma comprised 6 to 12 percent. Male to female ratio was 1.7 to 1 with male preponderance. Mean ages of the early gastric cancer was 49.0 years and most prevalent ages was 5th decade. Macroscopically type IIc was most prevalent, reaching 59.9 percent. Depressed type lesions was more frequent than elevated type lesions by four folds. The size of lesions less than 4 cm accounted for more than 80 percent. Most frequent site of lesions were lower third by the CMA classification and lesser curvature transectionally. Lymph node metastasis was observed in 10.9 percent of all cases and it was more frequent in large tumor size more than 4 cm, elevated type, and undifferentiated carcinoma. 5-year survival rate was 91.6 percent. Gastrofiberscopic examination was superior to that of radiological examination in the diagnosis of early gastric cancer.

Adult↗