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Biomedical subjects

S W Yang

Publications and source records attributed to S W Yang.

At least 37 records · Page 2Linked to original sources

Nitric oxide metabolites in induced sputum: a marker of airway inflammation in asthmatic subjects.

BACKGROUND AND OBJECTIVE: The role of nitric oxide (NO) needs to be further clarified in allergic inflammation. This study was designed to investigate the relationships between NO metabolites and eosinophil count, eosinophil cationic protein (ECP), interleukin (IL)-5 in induced sputum from asthmatics. METHODS: Hypertonic saline-induced sputum was obtained in 25 asthmatic subjects, among which 13 patients were examined before and after anti-asthmatic medications including steroid preparations. Ten normal subjects were enrolled as controls. Fresh expectorated sputum separated from saliva was treated with equal volume of dithiothreitol 0.1%, cytospinned for cell count, and the supernatant was collected for biochemical assay. NO metabolites were assayed by using modified Griess reaction. ECP was measured by fluoroimmunoassay, and detected IL-5 by a sandwich ELISA. RESULTS: Asthmatic subjects, compared with controls, had significantly higher concentration of NO metabolites (1035.4 +/- 125.3 vs 557.2 +/- 101.5 micromol/L, P < 0.01), higher percentage of eosinophils (25.6 +/- 4.6 vs 1.7 +/- 0.2%, P < 0.01), and higher levels of ECP (1117.8 +/- 213.9 vs 154.6 +/- 47.4 microg/L, P < 0.01) in the induced sputum. IL-5 was detected more frequently in asthmatic subjects than in control subjects (11/25 [44%] vs 1/10 [10%], P < 0.05). According to asthma severity, moderate to severe asthmatic subjects (n = 18) had higher level of NO metabolites (1143.8 +/- 156.3 vs 575.5 +/- 89.5 micromol/L, P < 0. 01), higher levels of ECP and IL-5 (P < 0.01, respectively) in the induced sputum than in those of mild asthmatic subjects (n = 7). NO metabolites, the percentage of eosinophils, the levels of ECP, and IL-5 were reduced following treatment with anti-asthmatic drugs (P < 0.01, respectively). There were significant positive correlations between NO metabolites and percentage of eosinophils or ECP (r = 0. 34, P < 0.05; r = 0.28, P < 0.05). Negative correlations were noted between FEV1, FEV1/FVC and proportion of eosinophils, ECP, or IL-5 levels. CONCLUSION: These findings confirmed that the level of NO metabolites was increased in the tracheobronchial secretion of asthmatic subjects and was paralleled with severity of asthma. Measurement of NO metabolites in induced sputum may be used for monitoring the degree of airway inflammation in asthmatics.

Adolescent↗

Malignant granular cell tumor at the retrotracheal space.

We report a case of an extremely rare neoplasm, malignant granular cell tumor (MGCT). The patient was a 21-year-old woman, who was 5 months pregnant. The tumor occurred in the retrotracheal space, extending from the level of the larynx to the thoracic inlet. In addition, there were multiple, variable-sized tumor nodules within both lung fields on chest CT scan. Histologically, tissue biopsied from the periphery of the tumor consisted of solid sheets of large ovoid cells with ample, eosinophilic cytoplasm, eccentric nuclei, and prominent nucleoli. Each cell showed slight atypism of the nuclei. There was a focal necrosis at the periphery of the lesion. These cells stained strongly for S-100 protein, neuron-specific enolase (NSE) and CD68. On electron microscopy, the tumor cells contained autophagic vacuoles. The patient refused further treatment and died 7 months later. The exact cause of death was not known. Until now, the diagnosis of MGCTs has been made only when metastasis and an aggressive clinical course are identified, although some observers advocate that some histologic features such as nuclear pleomorphism, necrosis, and the presence of any mitotic activity are indicative of malignancy. These histologic findings are not easily detectable in every case of MGCT, as in our case. So the diagnosis of a MGCT should be considered in cases with aggressive clinical findings and some histologic features, such as necrosis, nuclear atypism, and mitotic activities, which could suggest the malignant behavior of this neoplasm.

Adult↗

Retroperitoneal multilocular bronchogenic cyst adjacent to adrenal gland.

Bronchogenic cysts are generally found in the mediastinum, particularly posterior to the carina, but they rarely occur in such unusual sites as the skin, subcutaneous tissue, pericardium, and even the retroperitoneum. A 30-year-old Korean man underwent surgery to remove a cystic adrenal mass incidentally discovered during routine physical checkup. At surgery, it proved to be a multilocular cyst located in the retroperitoneum adjacent to the left adrenal gland. Microscopically, the cyst was lined by respiratory epithelium over connective tissue with submucous glands, cartilage and smooth muscle, thereby histologically confirming bronchogenic cyst. This is the first reported case of retroperitoneal bronchogenic cyst in an adult without other congenital anomalies in Korea.

Adrenal Glands↗

The effect of morphine on responses of mediodorsal thalamic nuclei and nucleus submedius neurons to colorectal distension in the rat.

In halothane-anesthetized rats, we characterized the responses of single neurons in the nuclei of medial thalamus (MT), specifically the mediodorsal thalamic nucleus (MD) and the nucleus submedius (Sm), to a noxious visceral stimulus (colorectal balloon distension, CRD), and studied the effects of intravenous morphine (Mor) on these responses using standard extracellular microelectrode recording techniques. 62 MD and 46 Sm neurons were isolated on the basis of spontaneous activity. 47 of the MD neurons (76%) responded to CRD, of which 70% had excitatory and 30% had inhibitory responses. 38 of the Sm neurons (83%) responded to CRD, of which 89% had excitatory and 11% had inhibitory responses. Responses of MD and Sm neurons excited by CRD were related significantly to distension pressure (20-100 mmHg), with maximum excitation occurring at 60 and 100 mmHg, respectively. MD neurons inhibited by CRD also had graded responses to graded CRD, with maximum inhibition occurring at 80 mmHg. The responses to noxious (pinch, heat) and nonnoxious (tap, brush) cutaneous stimuli were studied in 59 of the MD and 44 of the Sm neurons isolated. 22 of the MD neurons (37%) studied had cutaneous receptive fields, of which 59% were large and bilateral, 41% were small and usually contralateral receptive fields. 55% of these neurons were nociceptive-specific, 45% responded to both noxious and nonnoxious cutaneous stimulation. 29 of the Sm neurons (66%) studied had cutaneous receptive fields, of which 72% were large and usually bilateral, 14% were small and bilateral, 14% were small and contralateral receptive fields. 90% of these neurons were nociceptive-specific, 10% responded to both noxious and nonnoxious stimulation. No MD or Sm neurons responded exclusively to nonnoxious cutaneous stimulation. Mor (0.125, 0.25, 0.5 and 1 mg/kg I.V.) attenuated MD and Sm neuronal excitatory responses to CRD in a dose-dependent fashion, abolishing evoked activity with a dose of 0.5 mg/kg (p < 0.05) and 1 mg/kg (p < 0.05), respectively. Naloxone (0.4 mg/kg I.V.) reversed the effects of Mor. Mor and naloxone had no effects on spontaneous activity. These data support the involvement of MD and Sm neurons in visceral nociception, and are consistent with a role of Sm in affective-motivational, and MD in both sensory-discriminative and affective-motivational aspects of nociception.

Analgesics, Opioid↗

Combinations of HLA DR and DQ molecules determine the susceptibility to insulin-dependent diabetes mellitus in Koreans.

The association of HLA-DRB1 and DQB1 genes with IDDM in Koreans was assessed using 115 IDDM patients and 140 nondiabetic controls. DQB1*0201 is the only DQB1 allele positively associated with IDDM while DQB*0602, *0601 and *0301 are negatively associated. Three DRB1 alleles (DRB1*0301, DRB1*0407 and DRB1*0901) are positively associated while four DR allele groups (DRB1*15, DRB1*12, DRB1*10 and DRB1*14) are negatively associated. However, Haplotype analyses indicated that DQB1*0302, DRB1*0405 and DRB1*0401 may confer susceptibility because the DRB1*0405-DQB*0302 and DRB1*0401-DQB1*0302 haplotypes are positively associated with the disease. The lack of association in Koreans with the DQB1*0302 allele, which appears predisposing in studies of non-Orientals, is due to its strong linkage disequilibrium (LD) with the protective DRB1*0403 and *0406 alleles, while the lack of association with DRB1*0405 is because of its strong LD with the protective DQB1*0401 allele. Nine DR/DQ genotypes confer significantly increased risk to IDDM. Seven of the nine genotypes (DR3/4s, DR1/4s, DR4s/13, DR4s/8, DR4s/7, DR9/13 and DR3/9) were also found to be at high risk to IDDM in other populations, while the two others (DR1/9 and DR9/9) are only found in Koreans. Surprisingly, DR4/4 homozygotes are not associated with high risk to IDDM in Koreans. This observation can be explained by the high frequency of protective DR4 subtypes and the protective DQ alleles (0301 and 0401) associated with the susceptible DR4 alleles. Our analyses indicate that the counterbalancing act between susceptible DRB1 and protective DQB1, and vice versa, that has already been observed in Chinese and Japanese, is the major factor responsible for the low incidence of diabetes in Koreans.

Adolescent↗

ATP-sensitive K+ channels are involved in the mediation of intrathecal norepinephrine- or morphine-induced antinociception at the spinal level: a study using EMG planimetry of flexor reflex in rats.

The effects of intrathecally (IT) administered glibenclamide (Gli), an ATP-sensitive K+ (KATP) channel blocker, on the antinociception produced by IT norepinephrine (NE), serotonin (5-HT), morphine (Mor), or adenosine agonist, 5'-N-ethylcarboxamide adenosine (NECA) were investigated using integrated EMG measurement of hindlimb flexor reflex (FR) in lightly pentobarbital-anesthetized rats. The results showed that: 1) NE (3, 6, or 12 nmol) or 5-HT (60, 120, or 240 nmol) each produced a dose-dependent suppression of FR EMG, respectively; 2) pretreatment with Gli (5, 10, or 20 nmol) antagonized the NE (6 nmol)-induced antinociception in a dose-dependent manner and failed to modulate the 5-HT (120 nmol)-induced suppression of FR EMG; 3) pretreatment with Gli (5, 10, or 20 nmol) also antagonize the Mor (2 nmol)-induced suppression of FR EMG in a dose-dependent manner; 4) pretreatment with naloxone (Nal, 60, 120, or 240 nmol) also antagonize the NE (6 nmol)-induced suppression of FR EMG in a dose-dependent manner; and 5) NECA (0.5, 1.0, or 2.0 nmol) produced a dose-dependent suppression of FR EMG, while pretreatment with Gli (5, 10, or 20 nmol) failed to modulate the NECA (1.0 nmol)-induced suppression of FR EMG. The results show that (a) ATP-sensitive K+ channels are involved in the NE- and Mor-induced antinociception but not 5-HT- or NECA-induced antinociception at the spinal level; (b) endogenous opioids might act as a successor of NE and then activate KATP channels to producing the antinociception.

Adenosine Triphosphate↗

Three new ellagic acid derivatives from the bark of Eschweilera coriacea from the Suriname rainforest.

Bioassay-guided fractionation of Eschweilera coriacea collected in the lowland wet forest of Suriname yielded the new but only weakly active ellagic acid derivative eschweilenol A (1) and the two new but inactive ellagic acid derivatives eschweilenol B (2) and eschweilenol C (3). The four known compounds, sucrose, ellagic acid, 3-O-galloylepigallocatechin, and epigallocatechin, were also isolated. The structures of the three new compounds were determined by spectrometric methods, primarily from the HMQC, HMBC, NOESY, and ROESY NMR techniques, and chemical methods, including methylation and triethylsilylation. The location of a hydroxyl group in one ellagic acid derivative was determined by a new technique involving an NOE correlation of the protons of a triethylsilyl derivative with a proton on a neighboring aromatic ring.

Antifungal Agents↗

Mutation in the gene encoding the fibroblast growth factor receptor-3 in Korean children with achondroplasia.

BACKGROUND: Achondroplasia (ACH) is the most common form of osteochondrodysplasia, and is mostly associated with a point mutation in the gene on the transmembrane domain of fibroblast growth factor receptor-3 (FGFR-3) on chromosome 4p. METHODS: We investigated the mutations in the gene encoding FGFR-3 in 15 Korean children with ACH, using polymerase chain reaction (PCR) coupled with direct sequencing. RESULTS: In this study, all children with ACH showed the same mutation as those reported in France, USA and Japan; a G-->A transition at position 1138 of the coding sequence, resulting in the substitution of arginine for glycine at position 380 of the mature protein. CONCLUSIONS: This consistent point mutation of Korean children with ACH indicates there is no significant racial difference in the pathogenesis of ACH, compared with data from Caucasian and Japanese children with ACH.

Achondroplasia↗

ATP-sensitive potassium channels mediate norepinephrine- and morphine-induced antinociception at the spinal cord level.

The effects of intrathecally (i.t.) administered glibenclamide, a blocker of adenosine triphosphate-sensitive potassium ( KATP) channels, on antinociception produced by i.t. norepinephrine, morphine, or 5'-N-ethylcarboxamide adenosine, an adenosine agonist, were investigated using tail-flick assay. The results showed that: 1) i.t. norepinephrine (1 nmol), morphine (0.5 nmol) and 5'-N-ethylcarboxamide adenosine (0.5 nmol) elicited prolongation of tail-flick latency, 2) i.t. glibenclamide given in 2 different doses (5 and 10 nmol) exhibited no effects on tail-flick latency, 3) the antinociception produced by norepinephrine (1 nmol) and morphine (0.5 nmol) was blocked by glibenclamide in a dose-dependent manner, 4) glibenclamide failed to modulate the effects of 5'-N-ethylcarboxamide adenosine on tail-flick latency. These observations suggest that KATP channels may play an important role in norepinephrine- and/or morphine-induced antinociception at the spinal level.

Adenosine Triphosphate↗

Multiple early esophageal cancers arising from Barrett's esophagus, and a review of cases of early adenocarcinoma in Barrett's esophagus in Japan.

A case of early esophageal adenocarcinoma arising in Barrett's esophagus is reported. Many cases of Barrett's esophagus, which is considered a premalignant condition, have been reported in Western countries, but few cases have been reported in Japan. The patient, a 53-year-old man with nausea and vomiting, was a drinker (four glasses wine/day for about 30 years), but did not smoke. He had had a hiatal hernia of the esophagus. Since endoscopic biopsies demonstrated an early adenocarcinoma in Barrett's esophagus, subtotal esophagectomy was performed. In the resected esophageal material, Barrett's esophagus was seen to extend for 12 cm. In addition to the cancer detected preoperatively as a 0-IIc lesion (1.5 cm in diameter), a 0-IIb lesion (1.5 cm in diameter) was also detected in the postoperative survey. Both lesions were well differentiated adenocarcinoma that had invaded only into the lamina propria mucosa. The 23 cases of early adenocarcinoma in Barrett's esophagus that have been reported in Japan were reviewed, and it was learned that the present case is the second of multiple early cancer arising in Barrett's esophagus so far reported in Japan.

Adenocarcinoma↗

Locus coeruleus stimulation modulates the nociceptive response in parafascicular neurons: an analysis of descending and ascending pathways.

The nociceptive responses in parafascicular neurons (PF) were recorded and studied following electrical stimulation of locus coeruleus (LC) combined with intrathecal (IT) or intracerebroventricular (ICV) administration of phentolamine (Ph), an alpha-adrenoceptor antagonist. The results revealed the following. (1) Three different PF neuronal populations were observed according to their response pattern following noxious stimulation: nociceptive-on, nociceptive-off, and nonresponsive units. Only the nociceptive-on units were studied further. (2) The nociceptive discharges in majority of PF neurons (66/87) were inhibited by electrical stimulation of the LC. (3) The inhibitory effect of LC stimulation was prevented and even reversed by pretreatment of IT Ph (40 nmol) in 22 units, or by dorsolateral funiculi transection in 24 units tested. (4) The inhibitory effect of LC stimulation was strengthened by preadministration of ICV Ph (40 nmol) in 17 units tested. (5) ICV administration of norepinephrine (NE 30 nmol) resulted in PF neurons a biphasic response to nociceptive stimulation: an early brief inhibition and a late long-lasting facilitation. (6) Pretreatment of ICV Ph (40 nmol) prior to NE injection prevented the NE-induced biphasic response. The results suggest that stimulation of LC modulates the nociceptive response of PF neurons through both ascending and descending routes. These two diverse routes exert two different effects: a predominantly inhibitory role on the nociceptive transmission at the spinal cord level by descending NE-ergic fibers, and a facilitatory role on the responsiveness of PF to noxious inputs by ascending fibers.

Adrenergic alpha-Agonists↗

Spinonin, a novel glycoside from Ononis spinosa subsp. leiosperma.

The roots of Ononis spinosa subsp. leiosperma (Leguminosae) afforded a new glycoside, spinonin (1), possessing a novel skeleton, in addition to the known isoflavonoid glycoside, ononin [7beta-(glucosyloxy)formononetin] (2) and the known pterocarpan, 7-demethoxy-7-D-(glucosyloxy)homopterocarpin (3). The structure of the new isolate was elucidated by spectral methods including 1H and 13C NMR, COSY, APT, HETCOR, HMBC, NOESY, CD, FABMS, HRMS, EIMS, CIMS, and some chemical reactions. Spinonin was inactive against a number of human cancer cell lines and HIV-1 reverse transcriptase. The compounds 1 and 3 showed weak activity against Pseudomonas aeruginosa, whereas 2 was active against beta-hemolytic Streptococcus.

Acetylation↗

Metabolism studies of indole derivatives using a staurosporine producer, Streptomyces staurosporeus.

From a tryptophan metabolic study, 3-(hydroxyacetyl)indole, indole-3-carboxaldehyde, and o-aminobenzoic acid were obtained as tryptophan metabolites from a staurosporine (1) producer, Streptomyces staurosporeus. A new tryptamine metabolite, (3aR,8aS)-1-acetyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3- b]indol-3a-ol (2), was isolated along with Nb-acetyltryptamine using S. staurosporeus fed with tryptamine. The unusual compound 2 was proposed as a further metabolite of Nb-acetyltryptamine through an enzymatic oxidative cyclization. Examination of the metabolites from the feeding of 5- and 6-fluorotryptamines using the same microorganism afforded the two novel compounds 3 and 4 as the 5- and 6-fluoro derivatives of 2. However, 5-hydroxytryptamine failed to generate the 5-hydroxy derivative of 2. Indole-ring-substituted metabolites of staurosporine (1) were not observed.

Culture Media↗

Further metabolic studies of indole and sugar derivatives using the staurosporine producer Streptomyces staurosporeus.

During our continuing studies of staurosporine (1) biosynthesis and the metabolism of indole derivatives, three additional novel metabolites, beta-hydroxy-Nb-acetyltryptamine (7) and its 5- and 6-fluoro derivatives (8 and 9, respectively), were isolated, respectively, from the feeding of tryptamine and 5- and 6-fluorotryptamines using Streptomyces staurosporeus. In addition, two new 5-hydroxytryptamine (serotonin) metabolites, Nb-acetyltryptamine-5-O-beta-D-quinovopyranoside (11) and Nb-acetyltryptamine-5-O-alpha-L-rhamnopyranoside (12), were isolated along with 5-hydroxy-Nb-acetyltryptamine (10). From a glucose containing medium, 6-O-acetylglucose and its 13C uniformly labeled derivative were isolated from a culture of S. staurosporeus during biosynthetic studies of 1. In 2-deoxyglucose metabolism studies, 6-O-acetyl-2-deoxyglucose was isolated and identified as a metabolic product of 2-deoxyglucose. A copper-enzyme inhibitor, N,N-diethyldithiocarbamic acid, was evaluated for the accumulation of staurosporine intermediates; however, no modified staurosporines were observed.

Antimetabolites↗

Asterlingulatosides C and D, cytotoxic triterpenoid saponins from Aster lingulatus.

A further investigation of Aster lingulatus has led to the isolation of two additional novel triterpene saponins, asterlingulatoside C [3-O-beta-D-glucopyranosyl-3 beta, 16 alpha-dihydroxyolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha- L- arabinopyranoside] (1) and asterlingulatoside D [3-O-beta-D-glucopyranosyl-3 beta,16 alpha-dihydroxyolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L- rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside] (2). Elucidation of the structures of 1 and 2 was mainly based on FABMS and 1D and 2D homonuclear and heteronuclear NMR techniques. Compounds 1 and 2 showed good inhibitory activity against DNA synthesis in human leukemia HL-60 cells with IC50 values of 8.8 and 6.1 microM, respectively.

Antineoplastic Agents, Phytogenic↗

24-norhopene derivatives from Diatenopteryx sorbifolia.

Two new hopene derivatives, 3 beta,6 beta-dihydroxy-21 alpha H-24-norhopa-4(23),22(29)-diene (1) and 3 beta,5 beta-dihydroxy-6 beta-[(4-hydroxybenzoyl)oxy]-21 alpha H-24-norhopa-4(23),22(29)-diene (2), together with cleomiscosin B (3) and 5,6-dimethoxy-7-hydroxycoumarin (umckalin), were isolated from the timber of Diatenopteryx sorbifolia. This is the first isolation of the norhopene skeleton from nature. The structures of the isolates were established by spectroscopic analysis.

Acetylation↗

Molecular analysis of hypoxanthine guanine phosphoribosyltransferase (HPRT) gene in five Korean families with Lesch-Nyhan syndrome.

Lesch-Nyhan syndrome is caused by the complete deficiency of hypoxanthine guanine phosphoribosyl-transferase (HPRT). By the analysis of genomic DNA and mRNA using the polymerase chain reaction (PCR) technique coupled with direct sequencing, five independent mutations in HPRT genes have been identified in Korean Lesch-Nyhan families. Two novel mutations and three previously reported mutations have been found in five independent families. Heterozygous carriers were detected in all the families, and prenatal diagnosis was carried out in two families.

Exons↗