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Biomedical subjects

J K Cho

Publications and source records attributed to J K Cho.

10 recordsLinked to original sources
PubMed1999

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1994

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↗
PubMed1989

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↗
PubMed1983

Disulfiram and erythrocyte aldehyde dehydrogenase inhibition.

During disulfiram therapy erythrocyte aldehyde dehydrogenase (ALDH) was fully inhibited. The time for total loss of erythrocyte ALDH activity ranged from 36 to 120 hr. In contrast to the 85% recovery of in vitro disulfiram-inhibited ALDH activity, this in vivo disulfiram-ALDH inhibition could not be reversed by mercaptoethanol. It is proposed that the in vivo and in vitro mechanisms of ALDH inhibition by disulfiram differ. Erythrocyte ALDH activity can be readily monitored to determine patient compliance and is an accessible model for investigations of in vivo mechanisms of drug inhibition. Because the disulfiram-inhibited erythrocyte ALDH is not regenerated until new erythrocytes are made (120 days), a significant portion of the extrahepatic acetaldehyde metabolic capacity remains inhibited for long periods after disulfiram is discontinued. Thus, the recidivistic patient who discontinues disulfiram and waits several days (to regenerate liver ALDH activity) before drinking will be exposed to even higher ethanol-derived blood acetaldehyde levels than usual, which may induce further alcohol-associated organ damage and alcohol dependence.

Adult↗