Biomedical subjects

W S Choi

Publications and source records attributed to W S Choi.

At least 73 records · Page 4Linked to original sources

PubMed1999

Biochemical and pharmacological characteristics of a newly synthesized H+-K+ ATPase inhibitor, YJA20379-1, 2-amino-4,5-dihydro-8-phenylimidazole[2,1-b]thiazolo[5,4-g]benzothiazol e.

The biochemical and pharmacological characteristics of a newly synthesized H+-K+ ATPase inhibitor, 2-amino-4,5-dihydro-8-phenylimidazole[2,1-b]thiazolo[5,4-g]benzothiazole (YJA20379-1), were investigated. In the pig gastric microsomes, YJA20379-1 inhibited the gastric H+-K+ ATPase regardless of pH condition, IC50 values being 21 and 24 microM at pH 6.4 and 7.4, respectively. The inhibitory activity of YJA20379-1 was antagonized by dithiothreitol treatment but could not be reversed by dilution and washing of the enzyme preparation. In Sprague-Dawley rats, YJA20379-1, administered i.d., p.o, i.v., or s.c., significantly inhibited basal gastric acid secretion, with ED50 values of 4.7, 20.2, 6.3, and 13.4 mg/kg, respectively. The antisecretory action of YJA20379-1 was short lasting (less than 7 h at an oral dosing of 30 mg/kg). Oral administration of YJA20379-1 also prevented the formation of ethanol, indomethacin, and water immersion stress induced gastric lesions and mepirizole-induced duodenal ulcers in rats. Furthermore, YJA20379-1 accelerated the healing of acetic acid induced chronic gastric ulcers in rats. In conclusion, these results suggest that YJA20379-1 has a potent inhibitory activity on the gastric H+-K+ ATPase but much shorter duration of antisecretory action than omeprazole, thereby exerting its anti-ulcer effects partly with cytoprotective activity.

Animals↗

PubMed1998

Synthesis and evaluation of 2-amino-9-(3-hydroxymethyl-4-alkoxycarbonyloxybut-1-yl)purines as potential prodrugs of penciclovir.

A series of 2-amino-9-(3-hydroxymethyl-4-alkoxycarbonyloxybut-1-yl)purines (4-10) and 2-amino-9-(2-(2-oxo-1,3-dioxan-5-yl)ethyl)purine (1) were synthesized as potential prodrugs of penciclovir and evaluated for their oral penciclovir bioavailability in mice and rats. Treatment of 2-(2-benzyloxyethyl)propane-1,3-diol (11) with 1,1'-carbonyldiimidazole in THF followed by hydrogenolytic removal of the benzyl group of the resulting cyclic carbonate 12 gave 5-(2-hydroxyethyl)-1,3-dioxan-2-one (13). Mesylation of the alcohol 13 and then a coupling reaction of the resulting mesylate 14 with 2-amino-6-chloropurine using anhydrous Cs2CO3 in DMF afforded 2-amino-6-chloro-9-(2-(2-oxo-1,3-dioxan-5-yl)ethyl)purine (16) after purification by flash column chromatography on silica gel using EtOAc/MeCN/Et3N as eluent. Hydrogenation of the 6-chloro cyclic carbonate 16 followed by a ring-opening reaction of the 6-deoxy cyclic carbonate 1 in a mixture of an appropriate alcohol and CHCl3 using activated SiO2 as a Lewis acid afforded the corresponding alkyl monocarbonate derivatives 3-10 in fair to good yields. Of the prodrugs tested in mice, the isopropyl monocarbonate 6 achieved the highest mean urinary recovery of penciclovir (53%), followed in order by the propyl monocarbonate 5 (51%), the isopentyl monocarbonate 10 (51%), the ethyl monocarbonate 4 (50%), and famciclovir (48%). In rats, the methyl monocarbonate 3, 4, 6, the n-butyl monocarbonate 7, and 10 (39-41%) showed levels of mean urinary recovery of penciclovir similar to that from famciclovir (40%). The alkyl monocarbonates 4-10 were found to be quite stable in the aqueous buffer solutions, and among them, 6 was the most stable with the half-lives (t1/2) of 88, >200, 61, and 26 days at pH 1.2, 6.0, 7.4, and 8.0, respectively. In addition, 6 was highly soluble in H2O (138.8 mg/mL, 20 degrees C).

Acyclovir↗

PubMed1998

Changes in the midbrain-rostral forebrain dopamine circuitry in the cocaine-exposed primate fetal brain.

To ascertain cocaine's effects in the fetus, we developed a nonhuman primate model in which pregnant monkeys were administered cocaine (3 mg/kg i.m.) or saline four times a day from day 20 through days 40-70 of a 165-day gestation. At the time of cesarean section, plasma levels of cocaine in fetal blood were 231 +/- 70 ng/ml. Fetal brains were examined using immunocytochemistry, in situ hybridization, receptor autoradiography, and nuclease protection assay analysis. No differences were found in the expression of tyrosine hydroxylase and dopamine receptor mRNAs by days 40-45 of gestation. However, by day 60 the midbrain of monkeys exposed to cocaine had significantly reduced expression of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Moreover, dopamine D1 and D2 receptor mRNAs were significantly elevated in the rostral forebrain as were D1 and D2 receptor binding sites in days 60-70 cocaine-exposed fetuses. Cocaine treatment from day 20 to days 60 and 70 of gestation also significantly increased the mRNA concentrations of dynorphin and enkephalin in the rostral forebrain. These findings suggest that in utero cocaine exposure has profound effects on the developing dopamine neurocircuitry.

Amniotic Fluid↗

PubMed1998

Methylesters of L-arginine and N-nitro-L-arginine induce nitric oxide synthase in Staphylococcus aureus.

The presence of L-arginine methylester (AME), L-arginine ethylester (AEE), or N-nitro-L-arginine methylester (NAME) in the growth media of Staphylococcus aureus increased the nitric oxide synthase (NOS) activity approximately 5- to 14-fold. The increase of NOS activity was confirmed by two assay methods, namely assaying the formation of L-[3H] citrulline from L-[3H] arginine and NO formation. The increase of NOS activity was most likely due to increased de novo synthesis, demonstrated by Western immunoblot analysis. The addition of methanol to the culture medium also increased the NOS activity as much as that found with the above three compounds. Evidence is presented to show that AME, AEE, or NAME gave rise to the formation of methanol in vivo by the action of intracellular esterase(s) and that methanol is subsequently involved in the induction of NOS in this bacterial system.

Alcohols↗

PubMed1998

Effects of dopamine and estrogen on the regulation of Pit-1 alpha, Pit-1 beta, and PL-II gene expression in the rat placenta.

Pituitary-specific transcription factor Pit-1 regulates growth hormone and prolactin gene expression in the pituitary. Recently, Pit-1 was shown to be locally synthesized in the rat placenta and is involved in the regulation of rat placental lactogen (PL) gene expression. Pit-1 has three different splicing variants. They are well known as being biologically active. In the present study, we found that Pit-1 beta is also synthesized in the rat placenta and we tried to examine the effects of dopamine and estrogen on the regulation of Pit-1 alpha, beta and PL-II genes expression using the reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot hybridization. A dopamine receptor agonist, bromocriptine, significantly decreased placental Pit-1 alpha, beta, and PL-II mRNA levels. To examine the effect of estrogen on the gene expression of Pit-1 beta, pregnant female rats were ovariectomized (OVX) and injected daily with 17 beta-estradiol. OVX markedly lowered the amount of Pit-1 beta mRNA. Estrogen injection recovered the OVX-induced inhibition of Pit-1 beta mRNA level. Finally, we investigated the site-specific transcription of Pit-1 alpha and beta mRNA in the labyrinth zone and junctional zone of the placental in 15 and 20 days of gestation. The main site of Pit-1 alpha and beta synthesis was shifted from the junctional zone to the labyrinth zone from 15 to 20 days of gestation. Together, these data presume that Pit-1 beta may play a more important role in the placenta than in the pituitary and that Pit-1 may be involved in the regulation of the PL and prolactin-like peptide by estrogen and dopamine in the rat placenta.

Animals↗

PubMed1998

Tobacco industry promotion of cigarettes and adolescent smoking.

CONTEXT: Whether tobacco advertising and promotion increases the likelihood that youths will begin smoking has important public policy implications. OBJECTIVE: To evaluate the association between receptivity to tobacco advertising and promotional activities and progress in the smoking uptake process, defined sequentially as never smokers who would not consider experimenting with smoking, never smokers who would consider experimenting, experimenters (smoked at least once but fewer than 100 cigarettes), or established smokers (smoked at least 100 cigarettes). DESIGN: Prospective cohort study with a 3-year follow-up through November 1996. SETTING AND PARTICIPANTS: A total of 1752 adolescent never smokers who were not susceptible to smoking when first interviewed in 1993 in a population-based random-digit dial telephone survey in California were reinterviewed in 1996. MAIN OUTCOME MEASURE: Becoming susceptible to smoking or experimenting by 1996. RESULTS: More than half the sample (n=979) named a favorite cigarette advertisement in 1993 and Joe Camel advertisements were the most popular. Less than 5% (n=92) at baseline possessed a promotional item but a further 10%(n=172) were willing to use an item. While having a favorite advertisement in 1993 predicted which adolescents would progress by 1996 (odds ratio [OR] = 1.82; 95% confidence interval [CI], 1.04-3.20), possession or willingness to use a promotional item was even more strongly associated with future progression (OR=2.89; 95% CI, 1.47-5.68). From these data, we estimate that 34% of all experimentation in California between 1993 and 1996 can be attributed to tobacco promotional activities. Nationally, this would be over 700000 adolescents each year. CONCLUSION: These findings provide the first longitudinal evidence to our knowledge that tobacco promotional activities are causally related to the onset of smoking.

Adolescent↗

PubMed1998

Overexpression of HA-Bax but not Bcl-2 or Bcl-XL attenuates 6-hydroxydopamine-induced neuronal apoptosis.

Bax, a member of the Bcl-2 gene family, is known to promote apoptosis in many cases but to block cell death under certain conditions. To investigate the potential role of Bax in 6-hydroxydopamine (6-OHDA)-induced cell death, we first established and characterized a dopaminergic neuronal cell line (MN9D) stably overexpressing hemagglutinin epitope-tagged Bax (MN9D/HA-Bax) as well as control clones (MN9D/Neo). Treatment of MN9D/Neo cells with 6-OHDA induced typical apoptotic cell death accompanied by shrinkage of the cell, nuclear condensation, and DNA fragmentation as demonstrated by light microscopy and agarose gel analysis. Overexpression of HA-Bax in MN9D cells was shown to attenuate 6-OHDA-induced cell death as determined by the MTT reduction assay and agarose gel analysis for DNA fragmentation. Western blot analysis revealed that cleavage of poly(ADP-ribose)polymerase induced by 6-OHDA was attenuated in MN9D/HA-Bax cells. In contrast, overexpression of a well-known cell death-inhibiting protein such as Bcl-2 or Bcl-XL did not attenuate 6-OHDA-induced cell death. Interestingly, cell death induced by hydrogen peroxide (0.25-2.0 mM) was significantly accelerated, whereas the rate of cell death induced by menadione (10-50 microM) was not affected in MN9D/HA-Bax cells. Thus, our present data suggest that the functionally diverse roles of Bax may be determined by the type of stress applied to the cell.

Animals↗

PubMed1998

Biochemical and pharmacological properties of a new proton pump inhibitor, 2-amino-4,5-dihydropyrido[1,2-a]thiazolo [5,4-g] benzimidazole (YJA20379-5).

This study was designed to determine biochemical and pharmacological properties of a newly synthesized benzimidazole derivative, 2-amino-4,5-dihydropyrido [1,2-a] thiazolo [5,4-g] benzimidazole (YJA20379-5) in vitro and in vivo. In the leaky membrane vesicles of pig gastric mucosa, YJA20379-5 inhibited the K(+)-stimulated H+,K(+)-ATPase activity in a concentration- and time-dependent manner, with IC50 values being 43 microM and 31 microM at pH 6.4 and 7.4, respectively. YJA20379-5, given intraduodenally, had a potent inhibitory effect on the gastric acid secretion in pylorus-ligated rats. The ED50 value for acid secretion was 15.4 mg/kg. YJA20379-5, administered orally, also suppressed gastric damages induced by water-immersion stress, indomethacin and ethanol, and duodenal damage induced by mepirizole in rats; the ED50 values were 17.6, 4.7, 3.0 and 18.7 mg/kg, respectively. Furthermore, repeated oral administration of YJA20379-5 accelerated the spontaneous healing of acetic acid-induced gastric ulcers in rats. It is concluded that the antisecretory activity of YJA20379-5 appears to be associated with inhibition of H+,K(+)-ATPase, while its antigastric and antiduodenal lesion activities are primarily related to the antisecretory effect.

Animals↗

PubMed1998

Inhibitory action of YJA20379, a new proton pump inhibitor on Helicobacter pylori growth and urease.

The activities of two types of antiulcer agents against 9 strains of Helicobacter pylori (H. pylori) were determined by the agar dilution method. The antiulcer agents were YJA20379, a newly synthesized proton pump inhibitor developed by Yung-Jin Pharmaceutical company, and omeprazole. Both compounds were found to have significant activities against this organism. The MIC values of YJA20379 and omeprazole were 11.7 and 31.25 micrograms/ml, respectively. In addition, the inhibitory potency of both compounds was investigated on H. pylori urease which is believed to be an important colonization and virulence factor in the pathogenesis of gastritis and peptic ulcers. These compounds dose-dependently inhibited urease extracted with distilled water and their IC50 values were 16.4 x 10(-5) M and 14.3 x 10(-5) M, respectively. In addition, a pH-dependent study to determine whether inhibitory potency would be activated by acid condition was performed. It was found that unlike omeprazole, YJA20379 was not affected by acid condition. To determine the inhibition pattern and optimal concentration of substrate, kinetics were evaluated at various pH levels (pH 5.0, 7.0, and 8.5). The data show that YJA20379 noncompetitively inhibited H. pylori urease and KM/Ki values were 0.96 mM/60 microM (pH 5.0), 0.56 mM/141.5 microM (pH 7.0), and 1.94 mM/34 microM (pH 8.5), respectively. Based on data obtained, it is concluded that YJA20379 is a significant inhibitor of H. pylori growth and urease and therefore, taking these results into consideration, YJA20379 might be a beneficial therapy for gastritis and peptic ulcers induced by H. pylori.

Benzothiazoles↗

PubMed1998

Imaging of the neurological complications of infective endocarditis.

We describe the findings on CT or MRI in five patients with neurological symptoms and underlying infective endocarditis (IE). We noted the size, number, and distribution of lesions, the presence or absence of haemorrhage, and contrast enhancement patterns. The number of lesions ranged from 4 to more than 10 in each patient. Their size varied from punctate to 6 cm; they were distributed throughout the brain. The lesions could be categorized into four patterns based on imaging features. A cortical infarct pattern was seen in all patients. Patchy lesions, which did not enhance, were found in the white matter or basal ganglia in three. Isolated, tiny, nodular or ring-enhancing white matter lesions were seen in three patients, and parenchymal haemorrhages in four. In addition to the occurrence of multiple lesions with various patterns in the same patient, isolated, tiny, enhancing lesions in the white matter seemed to be valuable features which could help to differentiate the neurological complications of IE from other thromboembolic infarcts.

Adult↗

PubMed1998

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↗

PubMed1998

Distribution of the receptor for a novel peptide stimulating phosphoinositide hydrolysis in human leukocytes.

OBJECTIVES: Previously we reported that a synthetic peptide, WKYMVm, stimulates phosphoinositide (PI) hydrolysis in several hematopoietic cell lines and human neutrophils. In addition, the peptide induces superoxide generation in human neutrophils. The biochemical stimulation appeared to be mediated by specific receptors on leukocytes. In this report we try to find whether the specific receptor(s) exists on specific types of cells in human leukocytes. DESIGN AND METHODS: To study distribution of the peptide-specific receptors, we prepared a probe, biotin-labeled WKYMVm, and analyzed distribution of the peptide receptor using a biochemical study, cytochemical staining, and flow cytometric analysis. RESULTS: The peptide-specific receptors are expressed in several human leukocytes including granulocytes, monocytes, and B-lymphocytes but not T-lymphocytes and erythrocytes. CONCLUSIONS: These data suggest that the receptors for the peptide restricted to certain types of leukocytes and this specificity is probably related to the specific functions of the stimulated leukocytes.

Amino Acid Sequence↗

PubMed1998

Parental influences predict adolescent smoking in the United States, 1989-1993.

PURPOSE: To examine parental influences on two transitions in the adolescent smoking uptake process: from never having smoked to experimentation and from experimentation to established smoking. METHODS: Using data from the longitudinal Teenage Attitudes and Practices Survey of 1989-1993, we related perceived parental concern about their adolescents' future smoking, parental smoking status, problem-solving communication between parent and adolescent, demographics, and other factors at baseline to experimentation by follow-up among those who had never puffed on a cigarette (n = 4149). We also related these factors at baseline to reaching a lifetime level of smoking of at least 100 cigarettes by follow up among those who had experimented but smoked < 100 cigarettes (n = 2684) in univariate and multivariate analyses. RESULTS: Among never-smokers, baseline susceptibility to smoking and having male best friends who smoke predicted experimentation in the next 4 years. Among experimenters, susceptibility to smoking, having male or female best friends who smoked, and lack of parental concern about future smoking distinguished those who progressed to established smoking by follow-up. Furthermore, communicating with parents first about serious problems was protective against progression from experimentation to established smoking. CONCLUSION: Interventions aimed at reducing adolescent smoking should encourage cessation for parents who smoke and help parents communicate strong anti-smoking norms to children and adolescents and maintain strong lines of communication with them.

Adolescent↗

PubMed1998

Biochemical and pharmacological characteristics of 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline, a new proton-pump inhibitor, in rabbit gastric microsomes and in rats.

We have investigated the properties of the newly synthesized proton-pump inhibitor, 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline (YJA20379-6), on gastric mucosal proton-pump (H+/K+-ATPase) activity, gastric acid secretion and gastroduodenal lesions in experimental rats. YJA20379-6 markedly inhibited H+/K+-ATPase activity in rabbit isolated gastric mucosal microsomes, confirming its classification as a proton-pump inhibitor. The inhibitory efficacy of YJA20379-6 on the proton pump was approximately 14-times higher than that of omeprazole at pH 7.4. YJA20379-6 given intraduodenally had a potent inhibitory effect on gastric secretion in pylorus-ligated rats (ED50 22.9 mg kg(-1)) but was less active than omeprazole. Pretreatment of rats with YJA20379-6 dose-dependently protected the gastric mucosa from damage induced by water-immersion stress, indomethacin and absolute ethanol, and the duodenal mucosa from damage induced by mepirizole. Repeated administration of YJA20379-6 also dose-dependently accelerated the spontaneous healing of acetic acid-induced gastric ulcers. These results suggest that YJA20379-6 has potent anti-secretory and anti-ulcer effects which are exerted by suppression of H+/K+-ATPase activity in gastric parietal cells. YJA20379-6 might be useful for the clinical treatment of peptic ulcer diseases.

Animals↗

PubMed1998

The biochemical and pharmacological properties of a newly synthesized H+-K+ ATPase inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol-[1,2-a]benzimidazol e.

This study was designed to determine the effect of a newly synthesized proton pump inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol[1,2-a]be nzimidazole (YJA20379-2), on gastric H(+)-K(+) ATPase activity, acid secretion, and experimental gastroduodenal lesions or ulcers in rats. YJA20379-2 inhibited in a concentration-dependent manner the proton pump (H(+)-K(+) ATPase) activity in isolated hog gastric mucosal microsomes, therefore, confirming its classification as a proton pump inhibitor. The inhibitory efficacy of YJA20379-2 on the proton pump was about eight times higher than that of omeprazole at pH 7.4. The activity of the inhibited enzyme was not restored by dilution and washout method, so this implied that the inhibition of YJA20379-2 is not reversible. YJA20379-2, given intraduodenally or orally, potently suppressed acid secretion in pylorus-ligated rats, with ED50 values of 3.6 and 7.7 mg.kg(-1), respectively. Pretreatment with YJA20379-2 dose dependently protected the gastric mucosa from damage induced by absolute ethanol, water-immersion stress, indomethacin, and the duodenal mucosa from damage induced by mepirizole in rats, with ED50 values of 11.0, 21.0, 0.5, and 18.7 mg.kg(-1), respectively. Repeated administration of YJA20379-2 also dose dependently accelerated spontaneous healing of acetic acid induced gastric ulcers. These results suggest that YJA20379-2 has potent antisecretory and antiulcer effects, which are exerted by suppression of H(+)-K(+) ATPase activity in gastric parietal cells, such that YJA20379-2 may be useful for the clinical treatment of peptic ulcer diseases.

Animals↗

PubMed1998

Guanosine triphosphatase-activating protein-associated protein, but not src-associated protein p68 in mitosis, is a part of insulin signaling complexes.

The insulin receptor, following insulin stimulation of cells, triggers formation of various signaling complexes. In rat HTC hepatoma cells overexpressing normal human insulin receptors (HTC-IR), p85 regulatory subunit of phosphatidylinositol-3-kinase (PI3K) forms signaling complexes containing the insulin receptor, insulin receptor substrate 1 (IRS-1), guanosine triphosphatase-activating protein (GAP) and 60-70 kDa phosphotyrosine proteins (p60-70). In the present study, we demonstrate that p60-70 interacts directly with the p85 subunit via src homology 2 domain of the latter. Employing antibodies specific to two p85 isoforms, p85alpha and p85beta, we demonstrate that HTC-IR cells express both p85 isoforms, and these isoforms induce the formation of similar signaling complexes in response to insulin. p60-70, present in both alpha-p85alpha and alpha-p85beta immunoprecipitates, is a GAP-associated protein, but is distinct from the p68 src-associated protein in mitosis (Sam68) by several criteria. These data suggest that 1) GAP-associated protein, but not Sam68, is a part of insulin signaling complexes; and 2) p85alpha and p85beta form similar, but distinct, insulin receptor signaling complexes.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Effects of YJA20379-4 on gastric secretion, Helicobacter pylori growth and various gastric and duodenal lesions in rats.

Effects of a newly synthesized antiulcer agent, YJA20379-4, on gastric proton pump (H+/K+-ATPase) activity, Helicobacter pylori (H. pylori) growth, gastric acid secretion, and gastro-duodenal lesions, were examined in comparison with those of omeprazole. YJA20379-4 markedly inhibited the H+/K+-ATPase activity in a concentration-dependent manner and the inhibitory effect was increased under a weak acidic condition; the IC50 values were 32 and 81 microM at pH 6.4 and 7.4, respectively. The inhibition was completely antagonized by 0.5 mM dithiothreitol (DTT). In addition, YJA20379-4 showed a significant anti-H. pylori activity determined by the agar dilution method. The value of minimum inhibitory concentration (MIC, 3.9-11.7 microg/ml) was at least 3 times more potent than that of omeprazole. In pylorus ligated rats, YJA20379-4 inhibited basal gastric acid secretion when administered by the intraduodenal route (ED50: 23.6 mg/kg). In experimental ulcer models, YJA20379-4 administered by the oral route dose-dependently prevented the development of gastro-duodenal lesions in rats. Moreover, repeated administration of YJA20379-4 promoted the healing of gastric ulcers induced by acetic acid. On the basis of the data obtained, it is suggested that YJA20379-4 has a wide spectrum of antiulcer activities, and its mode of antiulcer actions is dependent on the inhibition of H+/K+-ATPase activity and H. pylori growth and the enhancement of a mucosal defense. Thus, YJA20379-4 might prove to be a beneficial therapy for gastritis and peptic ulcer diseases.

Animals↗

PubMed1998

Sinus histiocytosis with massive lymphadenopathy. Multiple skull involvements.

Sinus histiocytosis with massive lymphadenopathy is a non-neoplastic self-limiting disease of the bone marrow stem cell origin. It is characterized by painless, bilateral cervical lymphadenopathy accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate and hypergammaglobulinemia. Extranodal involvement including bone is rare. The patient is a 45-year -old female with multiple punch out lesions on her skull. MRI findings included iso-signal intensity mass at the diploid space on T1 weighted image and on T2 weighted image, mild high signal intensity was obtained. Histologically, the lesion showed proliferation of histiocytes in the fibroblastic background with formation of reactive germinal centers and many plasma cells. The histiocytes show round nuclei and occasional nucleoli and abundant cytoplasms. In area, there is lymphocytophagocytosis. Immunohistochemically, the histiocytes were positive for S-100 protein and lysozyme.

Female↗