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Biomedical subjects

H Kim

Publications and source records attributed to H Kim.

At least 505 records · Page 28Linked to original sources

Nitric oxide expression in airway epithelial cells in response to tubercle bacilli stimulation.

In order to investigate the role of airway epithelial cells in pulmonary tuberculosis, inducible nitric oxide synthetase (iNOS) expression and nitric oxide (NO) production were studied in A549 cells. Peripheral blood mononuclear cells (PBMC) from normal volunteers were separated and cultured for 24 h with LPS or tubercle bacilli (H37Rv, H37Ra). Thereafter, A549 cells were stimulated for another 24 h with culture supernatant fluids of PBMC. iNOS messenger RNA (mRNA) expression was measured with Northern blot analysis and NO production was measured with the Griess reaction, which can measure nitrite concentration. iNOS mRNA expression and NO production were minimal in the control cells. iNOS mRNA expression and NO production were significantly increased with LPS (P < 0.05) or tubercle bacilli (P < 0.01) stimulation. However, there was no difference in iNOS mRNA expression and NO production between H37Rv and H37Ra stimulations. Interestingly, iNOS mRNA expression and NO production were greater in A549 cells stimulated with tubercle bacilli-conditioned media than in the cells stimulated with LPS-conditioned media. IL-1beta, tumour necrosis factor-alpha and interferon gamma concentrations were increased in culture supernatant fluids of PBMC stimulated with tubercle bacilli. These findings suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis by producing NO. However, the role of airway epithelial cells, regarding the virulence of tubercle bacilli, was not clear in this study.

Cells, Cultured↗

Stenting therapy for stenosing airway disease.

Stenosing airway disease is classified as intraluminal obstruction, extrinsic compression, and malacia by the anatomical site of the lesion. Stenting therapy is indicated for symptomatic relief of life-threatening dyspnea caused by the last two types. Airway stents are made with metal mesh and/or silicone rubber, and currently more than 20 kinds of stent are available. The metal stent (e.g. Gianturco stent, Wallstent) is easy to insert, may not need general anesthesia, and has wider internal lumen. Because it is very hard to reposition or remove, it is mainly used in malignant airway obstruction. Among many kinds of silicone stent, the Dumon stent is most widely used for benign and malignant airway stenoses, but general anesthesia and rigid bronchoscopy are needed for insertion. It can be removed when the stenosing airway disease subsides completely. In many clinical studies, most patients (85-90%) improved immediately after stenting, and procedure-related mortality is low (< 3%) in experienced centers. Stent displacement, mucus impaction, and granulation tissue formation are potential complications. Stenting is one of many effective therapeutic modalities for stenosing central airway disease. Careful patient selection, experiences, and continuous development of new technology will bring better results.

Airway Obstruction↗

Relationship between fat distribution and lipid and apolipoprotein profiles in young teenagers.

The influence of obesity and fat distribution on serum levels of lipoprotein and apolipoprotein was investigated in 294 Japanese junior high school children (12-13 years of age). Serum levels of low-density lipoprotein cholesterol (LDLC) (P = 0.013), triglycerides (TG) (P = 0.0006), and apolipoprotein B (apoB) (P = 0.003), and the apoB/A-I ratio (P = 0.005) were significantly higher and serum levels of high-density lipoprotein cholesterol (HDLC) (P = 0.00003) and apoA-1(P = 0.003) were significantly lower in obese boys than in non-obese boys. The serum levels of TG (P = 0.013) and the apoB/A-I ratio (P = 0.011) were significantly higher and the serum levels of HDLC (P = 0.004) was significantly lower in obese girls than in non-obese girls. The LDLC/apoB ratio was lower in obese girls than in non-obese girls (P = 0.03). Obesity (> or = 20% of ideal weight) was strongly correlated with the serum levels of lipids and apolipoproteins in boys; this relationship was less clear in girls. The degree of obesity and the body mass index (BMI) were more strongly correlated with serum levels of lipids and apolipoproteins in boys than in girls. In boys, atherogenic lipoproteins and apolipoproteins, such as LDLC and apoB, showed a stronger correlation with the thickness of the triceps skinfold, while in girls the anti-atherogenic lipoproteins and apolipoproteins, such as HDLC and apoA-I, showed a stronger correlation with both the triceps and the subscapular skinfold thicknesses. In girls the relationships between the BMI and the degree of obesity and the thickness of the subscapular skinfold (S) thickness were similar to the relationships between those parameters and the triceps skinfold (T) thickness. In boys, these parameters showed a stronger correlation with the subscapular skinfold thickness than with the triceps skinfold thickness. The correlation coefficients for the relationships between skinfold thickness and lipid and apolipoprotein levels were similar to the coefficients for the relationships between skinfold thicknesses and the severity of obesity and the BMI. The distribution of central-type fat accumulation, which is indicated by the thickness of the subscapular skinfold, the S/T ratio and S-T value, was inversely correlated with the HDLC level in both boys and girls. The degree of obesity was strongly correlated with the atherogenic lipoprotein profile in boys, in part because the subscapular skinfold thickness was strongly correlated with the degree of obesity and the BMI. In girls, the correlations between indices of central-type obesity and atherogenic lipid and apolipoprotein profiles were stronger than in boys. These data suggest that childhood obesity may be an early cardiovascular risk factor.

Adipose Tissue↗

Protein tyrosine phosphatase 2 (SHP-2) moderates signaling by gp130 but is not required for the induction of acute-phase plasma protein genes in hepatic cells.

Signals propagated via the gp130 subunit of the interleukin-6 (IL-6)-type cytokine receptors mediate, among various cellular responses, proliferation of hematopoietic cells and induction of acute-phase plasma protein (APP) genes in hepatic cells. Hematopoietic growth control by gp130 is critically dependent on activation of both STAT3 and protein tyrosine phosphatase 2 (SHP-2). To investigate whether induction of APP genes has a similar requirement for SHP-2, we constructed two chimeric receptors, G-gp130 and G-gp130(Y2F), consisting of the transmembrane and cytoplasmic domains of gp130 harboring either a wild-type or a mutated SHP-2 binding site, respectively, fused to the extracellular domain of the granulocyte colony-stimulating factor (G-CSF) receptor. Rat hepatoma H-35 cells stably expressing the chimeric receptors were generated by retroviral transduction. Both chimeric receptors transmitted a G-CSF-induced signal characteristic of that triggered by IL-6 through the endogenous gp130 receptor; i.e., both activated the appropriate JAK, induced DNA binding activity by STAT1 and STAT3, and up-regulated expression of the target APP genes, those for alpha-fibrinogen and haptoglobin. Notwithstanding these similarities in the patterns of signaling responses elicited, mutation of the SHP-2 interaction site in G-gp130(Y2F) abrogated ligand-activated receptor recruitment of SHP-2 as expected. Moreover, the tyrosine phosphorylation state of the chimeric receptor, the associated JAK activity, and the induced DNA binding activity of STAT1 and STAT3 were maintained at elevated levels and for an extended period of time in G-gp130(Y2F)-expressing cells following G-CSF treatment compared to that in cells displaying the G-gp130 receptor. H-35 cells ectopically expressing G-gp130(Y2F) were also found to display an enhanced sensitivity to G-CSF and a higher level of induction of APP genes. Overexpression of the enzymatically inactive SHP-2 enhanced the signaling by the wild-type but not by the Y2F mutant G-gp130 receptor. These results indicate that gp130 signaling for APP gene induction in hepatic cells differs qualitatively from that controlling the proliferative response in hematopoietic cells in not being strictly dependent on SHP-2. The data further suggest that SHP-2 functions normally to attenuate gp130-mediated signaling in hepatic (and, perhaps, other) cells by moderating JAK action.

Acute-Phase Proteins↗

A novel electron transfer mechanism suggested by crystallographic studies of mitochondrial cytochrome bc1 complex.

The crystal structure of bovine mitochondrial cytochrome bc1 complex, an integral membrane protein complex of 11 different subunits with a total molecular mass of 242 kDa, demonstrated a tightly associated dimer consisting of three major regions: a matrix region primarily made of subunits core1, core2, 6, and 9; a transmembrane-helix region of 26 helices in the dimer contributed by cytochrome b, cytochrome c1, the Rieske iron-sulfur protein (ISP), subunits 7, 10, and 11; and an intermembrane-space region composed of extramembrane domains of ISP, cytochrome c1, and subunit 8. The structure also revealed the positions of and distances between irons of prosthetic groups, and two symmetry related cavities in the transmembrane-helix region upon dimerization of the bc1 complex. Extensive crystallographic studies on crystals of bc1 complexed with inhibitors of electron transfer identified binding pockets for both Qo and Qi site inhibitors. Discrete binding sites for subtypes of Qo site inhibitors have been mapped onto the Qo binding pocket, and bindings of different subtypes of Qo site inhibitors are capable of inducing dramatic conformational changes in the extramembrane domain of ISP. A novel electron transfer mechanism for the bc1 complex consistent with crystallographic observations is discussed.

Animals↗

Effect of nitric oxide on hydrogen peroxide-induced damage in isolated rabbit gastric glands.

The present study aims at investigating the effects of nitric oxide (NO) on hydrogen peroxide (H2O2)-induced damage in isolated rabbit gastric glands. NO synthesis modulators such as L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) and an NO donor, sodium nitroprusside, were added to isolated rabbit gastric glands exposed to H2O2, generated by glucose oxidase acting on beta-D-glucose. As a result, glucose/glucose oxidase caused an increase in lipid peroxide production and decreases in reduced glutathione (GSH) content, GSH peroxidase activity, nitrite release, and mucus secretion in gastric glands. The alterations in lipid peroxide production, GSH content, and mucus secretion were prevented by pretreatment with L-arginine, a substrate for NO synthase and sodium nitroprusside, but not by L-NAME. In conclusion, NO protects gastric glands from H2O2 by inhibiting lipid peroxidation and maintaining cellular GSH content and mucus secretion.

Animals↗

Evidence for a frizzled-mediated wnt pathway required for zebrafish dorsal mesoderm formation.

We have used zebrafish as a model system for the study of vertebrate dorsoventral patterning. We isolated a maternally expressed and dorsal organizer localized member of the frizzled family of wnt receptors. Wild-type and dominant, loss-of-function molecules in misexpression studies demonstrate frizzled function is necessary and sufficient for dorsal mesoderm specification. frizzled activity is antagonized by the action of GSK-3, and we show GSK-3 is also required for zebrafish dorsal mesoderm formation. frizzled cooperatively interacts with the maternally encoded zebrafish wnt8 protein in dorsal mesodermal fate determination. This frizzled -mediated wnt pathway for dorsal mesoderm specification provides the first evidence for the requirement of a wnt-like signal in vertebrate axis determination.

Amino Acid Sequence↗

Radiological findings in myxoid liposarcoma of the anterior mediastinum.

CT and MR findings of a rare myxoid liposarcoma involving the anterior mediastinum are reported. The mass was a low density lesion with calcific septations and some peripheral frond-like enhancement on CT. MRI showed heterogeneous intermediate to high signal intensity on T1 weighted images and high signal intensity on T2 weighted images. The signal of the mass was not suppressed on fat suppressed images.

Adult↗

Immunohistochemical study of protein kinase C in the testes of cattle and pigs.

We investigated the expression of novel protein kinase C (PKC) delta and theta in the testes of pigs and cattle using Western blot and immunohistochemical analysis. PKC delta and theta are recognized in the testes of pigs and cattle by Western blot analysis. We found in immunohistochemical study that PCK delta was localized in the spermatids of seminiferous tubules, but not in the interstitial cells, while PKC theta was recognized only in the interstitial cells of the testes of in both species. These findings suggest that PKC delta and theta play an important role in the development of spermatozoa and the regulation of androgen in the testicular interstitial cells (probably Leydig cells), respectively.

Animals↗

Bronchial stenosis due to anthracofibrosis.

STUDY OBJECTIVES: To define the clinical characteristics of the patients showing bronchoscopic findings of bronchial narrowing or obliteration with black pigmentation on overlying mucosa (we named this finding as "anthracofibrosis"), and to determine the association of anthracofibrosis with tuberculosis. PATIENTS AND METHODS: The subjects of this study consisted of 28 patients; 8 men and 20 women, ranging in age from 42 to 86 years. The distinctive clinical features, natures of bronchoscopic lesions, and radiologic findings were analyzed retrospectively and summarized. Bacteriologic studies and results of pathologic examinations were also assessed. RESULTS: Chief complaints were cough (20/28) and dyspnea on exertion (17/28). The abnormal bronchoscopic findings were identified most frequently in the right middle lobe bronchus (n=21/28) while more than one part of the bronchial tree was narrowed in 22 patients. Abnormalities of bronchial airways on CT were associated with peribronchial cuffs of soft tissue or surrounding lymph nodes. In 17 patients, active tuberculous infection was confirmed either bacteriologically (n=15) and/or histologically (n=8). Pathologic study of the lesion obtained by bronchoscopic biopsy or thoracotomy showed dense bronchial and/or peribronchial fibrosis with interspersed black pigments. CONCLUSIONS: These findings strongly suggest that bronchial stenosis or obliteration with anthracotic pigmentation in the mucosa was caused by a fibrotic response to active or old tuberculous infection. To prevent the spread of tuberculosis and avoid unnecessary invasive procedures, detailed examinations for the presence of active tuberculosis should be performed in patients with this unique bronchoscopic finding.

Adult↗

Androgens and masculinization of genitalia in the spotted hyaena (Crocuta crocuta). 1. Urogenital morphology and placental androgen production during fetal life.

According to common understanding of sexual differentiation, the formation and development of a penile clitoris in female spotted hyaenas requires the presence of naturally circulating androgens during fetal life. The purpose of the present study was to determine potential source(s) of such fetal androgens by investigating the timing of urogenital development and placental production of androgen during early and mid-gestation. Fetuses determined to be female by molecular techniques (lack of SRY gene) at days 33 and 48 of gestation had undifferentiated gonads, but the clitoris was already 'masculinized' and was generally similar to the phallus of a 50-day-old male fetus. Wolffian and Müllerian ducts terminated at the urogenital sinus in both sexes and a urethra was present along the entire length of the clitoris and penis. The adrenal gland was large and histologically differentiated at 33 days. Steroid gradients across the uterus (a drop in delta 4-androstenedione, with increases in oestrogen and androgen), and high androstenedione in ovarian veins indicated that ovarian androstenedione was metabolized and secreted as testosterone by the placenta throughout gestation. In vitro, whole or homogenized placentae at days 48 and 58 of gestation (110 days total) metabolized radiolabelled androstenedione into testosterone and oestradiol; the specific enzymatic activity of early placental tissues was higher than at later stages. A human placental homogenate had higher aromatase activity but did not produce testosterone unless aromatase was inhibited. Infusion of labelled androstenedione into the uterine arteries of hyaenas demonstrated the conversion of this substrate into testosterone and oestradiol and their secretion into the fetal circulation. Evidently, androgen is produced by the placenta and secreted into the fetal circulation from early in pregnancy when masculinization is first evident, before differentiation of the fetal ovary.

Androgens↗

The N-terminal portion of parathyroid hormone-related protein mediates the inhibition of apical Na+/H+ exchange in opossum kidney cells.

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) can activate a common receptor in several different cell types. Both PTH and N-terminal PTHrP peptides have been shown to acutely inhibit the apical Na+/H+ exchanger in the renal proximal tubule. In this study, the ability of various PTHrP fragments to inhibit apical Na+/H+ exchange was investigated. In addition, the signal transduction events associated with PTHrP inhibition of apical Na+/H+ exchange in polarized OK-P cells were characterized. Both PTHrP-(1-34)NH2 and recombinant full-length PTHrP-(1-141) inhibited apical Na+/H+ exchange activity by approximately 50%. These changes occurred in close temporal association with significant (threefold) increases in cellular cAMP accumulation. PTHrP-(1-34)NH2 had no effect on intracellular Ca2+, inositol phosphate production, or protein kinase C activity. PTHrP peptides, including PTHrP-(38-64)NH2, PTHrP-(67-86)NH2, PTHrP-(102-107)NH2, and PTHrP-(107-139)NH2, which lack the PTH-like N terminus, had no effect on the antiporter activity or cAMP accumulation. The results demonstrate that the N-terminal portion of the PTHrP molecule is responsible for inhibition of the apical Na+/H+ antiporter in OK-P cells.

Animals↗

Color-coded Doppler imaging of subclavian steal syndrome.

We examined the usefulness of color-coded Doppler echography for evaluating hemodynamics in patients with subclavian steal syndrome. Eighteen patients with subclavian steal syndrome, aged 54 to 77 years, were investigated. The diagnosis was confirmed by conventional angiography and pulsed-wave Doppler sonography. Using color-coded Doppler echography, the common, internal and external carotid and vertebral arteries and the subclavian artery on the affected side were visualized. In all patients, color-coded images of the antegrade common carotid arterial flow and the retrograde vertebral arterial flow on the affected side were obtained. Rapid flow through stenotic lesions and reflux from vertebral to subclavian arteries at the vertebral arterial ostia were observed. Color-coded Doppler echography is superior to duplex echography without the color-coded mode, because the flow through the affected vertebral and subclavian arteries can be easily traced in detail and the images are persuasive. This method is beneficial for diagnosing subclavian steal syndrome.

Aged↗

Female sex hormones and body mass in adolescent and postmenopausal Korean women.

A cross-sectional study was conducted to evaluate the relationship between body mass and serum level of female sex hormones among 153 adolescent girls, and 153 postmenopausal women in Korea. Information on lifestyles, and both menstrual and reproductive factors was collected by personal interview. Serum total estradiol (E2), progesterone (Pg), and sex hormone binding globulin (SHBG) concentrations were measured by radioimmunoassay. Multiple linear regression analysis was used to determine whether the hormonal levels would be affected by the obesity indices. Body weight and body mass index (BMI) were inversely related to SHBG level in both premenopausal (p<0.005) and postmenopausal women (p<0.005) after adjusting for age. E2 levels during any phase in premenopausal girls were not related to BMI, whereas heavier girls had significantly higher levels of late luteal-phase Pg (p<0.05). Taller postmenopausal women had lower E2 levels (p<0.05). Results on the association between SHBG and BMI are consistent with previous results in Caucasian women, and might suggest the potential role of bioavailable estradiol in breast carcinogenesis in pre- and post-menopausal women. The finding that progesterone might be related to body mass in premenopausal women should be pursued in further studies.

Adolescent↗