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Biomedical subjects

H H Kim

Publications and source records attributed to H H Kim.

At least 19 recordsLinked to original sources

Expression of Lewis antigens and their precursors in gastric mucosa: relationship with Helicobacter pylori infection and gastric carcinogenesis.

Lewis (Le)-associated antigens are carbohydrates that are related biochemically to the ABO blood groups, and may have a role in Helicobacter pylori adherence. To evaluate their relationship to clinicopathological outcomes, gastric Le expression, including type 1 precursor, type 1 H, Le(a), Le(b), Le(x), Le(y) and sialylated Le(a) (CA19-9), was evaluated immunohistochemically in 233 gastric biopsy specimens obtained at routine gastroscopy. Expression was also investigated in gastric tissues showing chronic gastritis, intestinal metaplasia, and carcinoma from 42 patients with gastric cancer. A polymerase chain reaction was performed for H. pylori and the bacterial babA2 gene. We identified type 1 precursor expression in 34.3%, type 1 H in 55.8%, Le(a) in 44.2%, Le(b) in 82.0%, Le(x) in 44.2%, Le(y) 56.7%, and CA19-9 in 16.3% of the 233 gastric biopsy specimens. Expression of type 1 H, Le(b), and CA19-9 was significantly associated with H. pylori infection and histological features (p < 0.05), and expression of type 1 H was an independent predictive factor for H. pylori infection by multivariate logistic regression (p = 0.020). Positivity for the babA2 genotype correlated significantly with H. pylori infection and type 1 H expression in gastric biopsy specimens (p < 0.05). The babA2 genotype was more frequent in gastric mucosa from the gastric cancer patients than in gastric biopsy specimens from routine gastroscopy (p = 0.009). In the 42 gastric cancer patients, the frequency of type 1 precursor, Le(a), and Le(x) expression was significantly higher in intestinal metaplasia and carcinoma than in chronic gastritis (p < 0.05), but the frequency of type 1 H and Le(b) expression was significantly lower in intestinal metaplasia and carcinoma (p < 0.05). In conclusion, Le expression, especially that of type 1 H, was significantly associated with clinicopathological features. In gastric cancer patients, Le expression was altered in intestinal metaplasia and carcinoma in comparison with chronic gastritis.

Adhesins, Bacterial↗

Cavernous haemangioma of the breast.

Vascular tumours of the breast are rare and most can be classified as either angiosarcomas or haemangiomas. Cavernous haemangiomas are the most common form of mammary haemangioma. We describe a case with unilateral whole breast involvement without associated calcifications, studied with mammography, ultrasound and MRI.

Adolescent↗

Small cell carcinoma of the colon: barium study and CT findings.

Extrapulmonary small cell carcinoma is a rare neoplasm. It is an aggressive malignant tumour characterized by rapid local progression and early metastasis. We report a case of small cell carcinoma arising in the transverse colon in a 34-year-old man who presented with epigastric pain. On CT, a poorly enhancing bulky mass encircling the transverse colon with extensive regional lymph node metastases was observed. A segmental annular narrowing with thick interhaustral folds of the transverse colon was found by barium enema examination. This is the first report of barium study and CT findings of extrapulmonary small cell carcinoma of the colon.

Adult↗

Three-dimensional reconstructed images using multidetector computed tomography in evaluation of the biliary tract.

The recent development of multidetector computed tomography (MDCT) and the parallel escalation in the capabilities of the workstation allow the use of high-quality multiplanar and three-dimensional reconstruction images. As a noninvasive technique, MDCT dedicated to the biliary tract represents an alternative to magnetic resonance cholangiography. The usefulness of three-dimensional reconstructed images using MDCT in evaluating biliary tract abnormality is illustrated.

Biliary Tract↗

Expression of the secreted factors noggin and bone morphogenetic proteins in the subependymal layer and olfactory bulb of the adult mouse brain.

The antagonism between noggin and the bone morphogenetic proteins (BMPs) plays a key role during CNS morphogenesis and differentiation. Recent studies indicate that these secreted factors are also widely expressed in the postnatal and adult mammalian brain in areas characterized by different types of neural plasticity. In particular, significant levels of noggin and BMP expression have been described in the rodent olfactory system. In the mammalian forebrain, the olfactory bulb (OB) and associated subependymal layer (SEL) are documented as sites of adult neurogenesis. Here, using multiple approaches, including the analysis of noggin-LacZ heterozygous mice, we report the expression of noggin and two members of the BMP family, BMP4 and BMP7, in these regions of the adult mammalian forebrain. We observe that along the full extent of the SEL, from the lateral ventricle to the olfactory bulb, noggin and BMP4 and 7 are mainly associated with the astrocytic glial compartment. In the OB, BMP4 and 7 proteins remain primarily associated with the SEL while strong noggin expression was also found in cells located in different OB layers (i.e. granule, external plexiform, glomerular layers). Taken together our data lead us to hypothesize that within the SEL the antagonism between noggin and BMPs, both produced by the glial tubes, act through autocrine/paracrine inductive mechanisms to maintain a neurogenetic environment all the way from the lateral ventricle to the olfactory bulb. In the OB, their expression patterns suggest multiple regulatory roles on the unusual neural plasticity exhibited by this region.

Animals↗

Delayed hemolytic transfusion reaction due to anti-Fyb caused by a primary immune response: a case study and a review of the literature.

Delayed hemolytic transfusion reactions (DHTRs) usually occur between 3 and 14 days posttransfusion as a result of a secondary immune response, with a drop in Hb level, fever, jaundice, or hemoglobinuria. DHTRs caused by a primary immune response are particularly rare events, and only a few reports have been known. In this report, we describe an unusual case of a DHTR caused by anti-Fyb in a 42-year-old man, who had no prior history of transfusion. Although it seems to be a rare phenomenon, we suggest that DHTRs by a primary immune response may be considered even in the case of the patient who had typical evidence of hemolysis but who had no previous transfusion history.

Adult↗

Lactacystin augments the sulindac-induced apoptosis in HT-29 cells.

The present study was conducted to explore the potential role of proteasome pathway in NSAIDs-induced apoptosis. We employed sulindac as a NSAID, and chose the lactacystin for inhibition of proteasome activity. Assessment of apoptosis and proteasome activity assay were undertaken. We demonstrated that sulindac treatment resulted in a decrease of proteasome activity, and that the co-treatment of a proteasome inhibitor lactacystin potentiated the extent of sulindac-induced apoptosis in HT-29 cells by augmentation of the decrease in proteasome activity. Elucidation of the mechanism underlying the regression of colon cancers by combinations of sulindac and lactacystin seems to be an immediate challenge for the near future.

Acetylcysteine↗

The natural history of hydronephrosis after radical hysterectomy with no intraoperatively recognisable injury to the ureter: a prospective study.

OBJECTIVE: To investigate, in a prospective study, the natural history of hydronephrosis of the urinary tract after radical hysterectomy. PATIENTS AND METHODS: From December 1997 to March 2001, 34 patients with localized cervical cancer underwent radical hysterectomy by one gynaecologist, with no intraoperatively identifiable injury to the ureter. Intravenous urography was used routinely before and at 2 and 4 weeks after surgery. The degree of hydronephrosis was graded I-IV. RESULTS: Urography before surgery showed no abnormal finding in any of the patients, except in one with a unilateral duplex kidney. Hydronephrosis was found in 10 units in the upper tract (grade II in eight, III in one and IV in one) in seven patients (21%) 2 weeks after surgery (one right, three left and three bilateral). All the ureteric narrowing was in the distal ureter. The hydronephrosis disappeared in four units in three patients, but became worse in two units in two patients with bilateral pathology in the fourth week. At 3 months after surgery no hydronephrosis had deteriorated and the hydronephrosis in all units had disappeared by 6 months. The presence of hydronephrosis was significantly correlated with pathological stage and age (P < 0.05). CONCLUSION: Hydronephrosis was detected after radical hysterectomy even with no intraoperatively recognisable injury to the ureter, but in most the hydronephrosis improved spontaneously and needed no ureteric stenting or surgical intervention.

Adult↗

The phosphatidylinositol 3-kinase, p38, and extracellular signal-regulated kinase pathways are involved in osteoclast differentiation.

Phosphatidylinositol 3-kinase (PI 3-kinase) and mitogen-activated protein kinases (MAPKs) have been implicated in diverse cellular functions, including proliferation, migration, and survival. In this study, we examined the involvement of these kinases in osteoclast differentiation by employing specific inhibitors of the kinases. The osteoclast differentiation was assessed in three different culture systems: a coculture of mouse bone marrow cells with mouse calvarial osteoblasts, a mouse bone marrow cell culture in the presence of receptor activator of NF-kappaB ligand (RANKL) and macrophage-colony stimulating factor (M-CSF), and a culture of bone-resident osteoclast precursor cells driven by RANKL and M-CSF. LY294002, a specific inhibitor of PI 3-kinase, potently inhibited osteoclast differentiation in all culture systems when assessed by both tartrate-resistant acid phosphatase (TRAP) staining and dentine resorption assays. Inhibition of p38 MAPK by SB202190 resulted in a strong suppression in the exogenous RANKL dependent mouse bone marrow and bone resident precursor cell cultures. Another MAPK pathway inhibitor (PD98059), which blocks the activation of extracellular signal-regulated kinase (ERK) by inhibiting the upstream kinase MAPK-ERK kinase (MEK) 1, exerted an inhibitory effect on osteoclast differentiation only at the highest concentration tested (30 micromol/L) in many cases. Whether the signaling pathways involving these kinases are activated by RANKL was also examined. The RANKL-stimulated phosphorylation of Akt, a downstream target of PI 3-kinase, and that of ERK were observed. RANKL also stimulated the activity of p38. These results suggest that PI 3 kinase, p38, and ERK play roles in osteoclast differentiation, at least in part, by participating in RANKL signaling.

Animals↗

ERK MAP Kinase is required in 1,25(OH)2D3-induced differentiation in human osteoblasts.

Expression of alkaline phosphatase(ALP)activity represents a key event during the differentiation processes of osteoblasts, and the level of ALP activity has been routinely used as a relative measure of differentiation stages of osteoblasts. In human osteoblasts, we showed that vitamin D3 analogue, 1,25(OH)2D3, had a stimulatory effect on ALP activity after 3 days, compared with control. The treatment of PD098059, an ERK MAP Kinase inhibitor, had a reducing effect on ALP activity, a differentiation marker in 1,25(OH)2D3-treated primary human osteoblasts. However, SB203580, a potent p38 MAP Kinase inhibitor, had no effect on the differentiation in this system. This indicates that ERK, not p38, is directly related to 1,25(OH)2D3-stimulated ALP activity in primary human osteoblasts. These results also show that the vitamin D3 analogue stimulates ERK1 activation in primary human osteoblasts. This finding provides one of signaling pathways for differentiation in primary human osteoblasts.

Alkaline Phosphatase↗

Synthesis and biological activity of disubstituted 4,5-polymethylenepyrazoles as selective cyclooxygenase-2 inhibitors.

A series of 1,3- and 2,3-disubstituted 4,5-polymethylenepyrazole derivatives were prepared and their inhibitory activities on cyclooxygenase-2 were evaluated. Among the compounds prepared, 1,3-isomer, 3-cyclohexyl-l-(4-fluorophenyl) 4,5-trimethylenepyra-zole (5be) showed the most potent (IC50 = 0.008 microM) inhibitory activity with little selectivity (13-fold) on cyclooxygenase-2.

Animals↗

A novel leucine-rich repeat protein (LRR-1): potential involvement in 4-1BB-mediated signal transduction.

4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is induced on CD4+ and CD8+ T cells upon engagement of the T cell receptor (TCR)/ CD3 complex with the antigen bound to MHC. 4-1BB plays an important role in transmitting costimulatory signal during T cell activation. However, 4-1BB-mediatded signal transduction pathways have remained elusive. We conducted the yeast two-hybrid screening to identify intracellular signaling molecules that associate with 4-1BB. A novel leucine-rich repeat (LRR)-containing protein, herein named LRR-1, was found to specifically interact with the cytoplasmic domain of 4-1BB. Overexpression of LRR-1 suppressed the activation of NF-KB induced by 4-1BB or TNF receptor-associated factor (TRAF) 2. In addition, LRR-1 down-regulated JNK1 activity was induced by 4-1BB. These results indicate that LRR-1 negatively regulates the 4-1BB-mediated signaling cascades which result in the activation of NF-kappaB and JNK1.

Amino Acid Sequence↗

Tumor necrosis factor-alpha supports the survival of osteoclasts through the activation of Akt and ERK.

Differentiated osteoclasts have a short life span. We tested various cytokines and growth factors for the effects on the survival of purified mature osteoclasts. In the absence of any added factors, osteoclasts exhibited the survival rate of less than 25% after a 24-h incubation. Among the tested factors, tumor necrosis factor-alpha (TNF-alpha) was found to increase the survival rate to approximately 80%. The TNF-alpha-enhanced survival of osteoclasts appeared to be associated with reduction in apoptosis and suppression of caspase activation. The antiapoptotic signaling pathways involved in the TNF-alpha-induced osteoclast survival were investigated. TNF-alpha treatment increased the phosphorylation of Akt in osteoclasts, which was suppressed by a phosphatidylinositol 3-kinase inhibitor LY294002 and an Src family kinase-selective inhibitor PP1. These inhibitors also attenuated the TNF-alpha stimulation of osteoclast survival. In addition an increase in the phosphorylation of ERK was observed upon TNF-alpha stimulation. PD98059, a specific inhibitor of the ERK-activating kinase MEK-1, abolished the TNF-alpha-induced ERK phosphorylation and osteoclast survival, and in these responses the involvement of Grb2 and ceramide was observed. These results suggest that TNF-alpha promotes the survival of osteoclasts by engaging the phosphatidylinositol 3-kinase Akt and MEK/ERK signaling pathways.

Adaptor Proteins, Signal Transducing↗

FLASH coordinates NF-kappa B activity via TRAF2.

FLASH is a protein recently shown to interact with the death effector domain of caspase-8 and is likely to be a component of the death-inducing signaling complex in receptor-mediated apoptosis. Here we show that antisense oligonucleotide-induced inhibition of FLASH expression abolished TNF-alpha-induced activation of NF-kappaB in HEK293 cells, as determined by luciferase reporter gene expression driven by a NF-kappaB responsive promoter. Conversely, overexpression of FLASH dose-dependently activated NF-kappaB, an effect suppressed by dominant negative mutants of TRAF2, NIK, and IKKalpha, and partially by those of TRAF5 and TRAF6. TRAF2 was co-immunoprecipitated with FLASH from the cell extracts of HEK293 cells or HeLa cells stably expressing exogenous FLASH (HeLa/HA-FLASH). Furthermore, serial deletion mapping demonstrated that a domain spanning the residues 856-1191 of FLASH activated NF-kappaB as efficiently as the full-length and could directly bind to TRAF2 in vitro and in the transfected cells. Taken together, these results suggest that FLASH coordinates downstream NF-kappaB activity via a TRAF2-dependent pathway in the TNF-alpha signaling.

Animals↗

Characterization of mouse brain-specific angiogenesis inhibitor 1 (BAI1) and phytanoyl-CoA alpha-hydroxylase-associated protein 1, a novel BAI1-binding protein.

Previously, PAHX-AP1 (PAHX-associated protein 1) was isolated as a novel protein to interact with Refsum disease gene product (phytanoyl-CoA alpha-hydroxylase, PAHX) and specifically expressed in mouse brain. PAHX-AP1 is also suggested to be involved in the development of the central neurologic deficits of Refsum disease. To clarify its function, we have searched for proteins that associate with PAHX-AP1 via yeast two-hybrid system. We found that PAHX-AP1 interacts with the cytoplasmic region of human brain-specific angiogenesis inhibitor 1 (hBAI1), and isolated murine homolog of hBAI1. Structural analysis of the PAHX-AP1 with three reported hBAI-associated proteins (BAP) revealed no homology among them, and we designated PAHX-AP1 as BAP4. The ability of BAP4 to interact with BAI1 was confirmed by pulling-down BAI1 with GST-BAP4 protein and immunoprecipitation study using brain lysate. Northern and Western blot analyses demonstrated a unique pattern of BAI1 expression in the brain. The peak level of BAI1 was observed 10 days after birth. In situ hybridization analyses of the brain showed the same localization of BAI1 as BAP4, such as most neurons of cerebral cortex, hippocampus, and V, VI, VII, VIII, and XII nuclei. Because BAI1 possessed thrombospondin-type 1 repeats in its extracellular region, changes of BAI1 expression were examined in the focal cerebral ischemia model. The BAI1 expression decreased on the ischemic side after 24 h but BAP4 was not changed after the time-course of ischemia. Our results indicate that expression and localization of BAI1 in the brain is correlated with BAP4, and that BAI1 is involved in inhibition of angiogenesis and neuronal differentiation.

Angiogenesis Inhibitors↗

Preventing labyrinthitis ossificans: the role of steroids.

OBJECTIVE: To identify a possible relationship between the administration of steroids at the time of diagnosis of bacterial meningitis and the development of labyrinthitis ossificans. DESIGN: Retrospective analysis of the charts of 38 children requiring cochlear implantation who presented with bacterial meningitis and then developed bilateral profound deafness. The patients' charts were reviewed for age at diagnosis, the type of antibiotic administered, and the administration, dosage, and duration of steroid (dexamethasone) therapy. Labyrinthitis ossificans was established by preoperative computed tomographic and/or magnetic resonance imaging and by the intraoperative findings as described in the operative report. PATIENTS AND METHODS: Patients were 38 children who received cochlear implantation by a single senior otolaryngologist for bacterial meningitis-related deafness. Ten patients' charts (26%) were available for full review; 9 of these 10 patients had documented pneumococcal meningitis and the other patient had Haemophilus influenzae-type meningitis. RESULTS: One of the 6 patients who received steroid therapy at the time of initial illness had documented evidence of labyrinthitis ossificans either radiographically or at the time of surgery. All 4 patients who failed to receive steroid therapy developed labyrinthitis ossificans. The results achieve statistical significance by chi2 analysis and a t test (P<.01). CONCLUSION: The results of this retrospective study are highly suggestive of a role for steroids in preventing the development of labyrinthitis ossificans in children with pneumococcal meningitis.

Anti-Inflammatory Agents↗