Biomedical subjects

H Kim

Publications and source records attributed to H Kim.

At least 379 records · Page 21Linked to original sources

PubMed1999

Cultures of astrocytes and microglia express interleukin 18.

Interleukin 18 (IL-18 or interferon-gamma inducing factor) is a recently discovered pro-inflammatory cytokine and powerful stimulator of the cell-mediated immune response. IL-18 is produced by several sources including monocytes/macrophages, keratinocytes and the zona reticularis and zona fasciculata of the adrenal cortex. IL-18 occurs in brain but its cellular source in the CNS has never been investigated. The presence of IL-18 and its response to stimulation in the brain was tested with primary cultures of microglia, astrocytes and hippocampal neurons. IL-18 mRNA was present in astrocytes and microglia, but not in neurons. The endotoxin lipopolysaccharide (LPS) did not affect IL-18 in astrocytes, but LPS robustly increased IL-18 mRNA in microglia. IL-18 protein was constitutively expressed in astrocytes and induced in microglia by LPS. The levels of interleukin-1beta converting enzyme (ICE), an activating enzyme, and caspase 3 (CPP32), an inactivating enzyme, were assessed to investigate the presence of the appropriate processing enzymes in the cultured cells. ICE was present at constitutive levels in microglia and astrocytes suggesting that these cell types may produce and secrete matured IL-18. Active forms of CPP32 were not detectable in either cell type indicating the absence of a degradative pathway of IL-18. The present results demonstrate that microglia and astrocytes are sources of brain IL-18 and add a new member to the family of cytokines produced in the brain.

Animals↗

PubMed1999

The STAT3-independent signaling pathway by glycoprotein 130 in hepatic cells.

Interleukin (IL)-6 is a major regulator of hepatic acute-phase plasma protein (APP) genes. The membrane-proximal 133-amino acid cytoplasmic domain of glycoprotein (gp) 130, containing one copy of the Box3 motif, is sufficient to transmit a productive signal to endogenous APP genes in rat hepatoma H-35 cells. In contrast, a mutant gp130 domain lacking the Box3 motif activates Janus kinases to a normal level but fails to activate signal transducer and activator of transcription 3 and to up-regulate a number of APP genes, including thiostatin, fibrinogen, hemopexin, and haptoglobin. However, in the absence of Box3, gp130 still stimulates the expression of alpha2-macroglobulin and synergizes with IL-1 to up-regulate alpha1-acid glycoprotein. The Box3 motif is not required for activation of the SH2-containing protein tyrosine phosphatase 2 or the mitogen-activated protein kinase (MAPK), nor is the immediate induction of egr-1 and junB significantly altered. Surprisingly, gp130 without any functional Box3 stimulates prolonged activation of MAPK, leading to an extended period of up-regulation of egr-1 and to an extracellularly regulated kinase-mediated reduction in the IL-6-stimulated production of thiostatin. IL-6 reduces proliferation of H-35 cells through signaling by the Box3. In addition, cells expressing Box3-deficient gp130 showed distinct morphologic changes upon receptor activation. Taken together, these results indicate that Box3-derived and Box3-independent signals cooperate in the control of hepatic APP genes and that Box3 may be involved in the modulation of MAPK activity in gp130 signaling.

Acute-Phase Proteins↗

PubMed1999

Tumorigenicity of mouse thymoma is suppressed by soluble type II transforming growth factor beta receptor therapy.

Many types of tumor cells overexpress transforming growth factor beta (TGF-beta), which is believed to promote tumor progression. We hypothesized that overexpression of the extracellular region of the type II TGF-beta receptor (soluble TbetaRII) would compete for or block TGF-beta binding to TbetaRs on immune cells, preventing TGF-beta-mediated immunosuppression and consequently resulting in the eradication of tumor cells. We tested this in the mouse thymoma cell line EL4, which has been reported to suppress cellular immunity by secreting a large amount of TGF-beta. Transduction of EL4 with recombinant retrovirus encoding soluble TbetaRII resulted in the secretion of heterogeneously glycosylated, 25 to 35 kDa truncated TbetaRII. Inoculation of 1 x 10(4) to 5 x 10(4) soluble TbetaRII-modified EL4 cells (EL4/Ts, EL4 cells transduced with recombinant retrovirus encoding soluble TbetaRII and neomycin resistance gene) s.c. to mice showed reduced tumorigenicity, as indicated by lower overall tumor incidence (7%, 1 of 14; P < 0.001) compared with unmodified EL4 (100%, 9 of 9) or vector-modified EL4 cells (EL4/neo, EL4 cells transduced with recombinant retrovirus encoding neomycin resistance gene; 100%, 4 of 4). Administration of mitomycin C-treated EL4/Ts cells (1 x 10(6)) after EL4 inoculation (1 x 10(4)) reduced tumor incidence from 100% (5 of 5 in mice inoculated with mitomycin C-treated EL4/neo) to 40% (4 of 10, P < 0.05), indicating that supply of soluble TbetaRII could actually block TGF-beta-mediated tumorigenesis. In vitro tumor cytotoxicity assays revealed 3-5-fold higher cytotoxic activity with lymphocytes from EL4/Ts-bearing mice compared with those from EL4- or EL4/neo-bearing mice, indicating that the observed tumor rejection was mediated by restoration of the tumor-specific cellular immunity. These data suggest that expression of soluble TbetaRII is an effective strategy for treating highly progressive tumors secreting TGF-beta.

Animals↗

PubMed1999

Pathogenesis of non-insulin-dependent (type II) diabetes mellitus (NIDDM) - genetic predisposition and metabolic abnormalities.

Non-insulin-dependent diabetes mellitus (NIDDM), also known as type II diabetes, is characterized by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with microvascular, macrovascular, and neuropathic complications. NIDDM is a complex disease with many causes. Both genetic and environmental factors play important roles in the pathogenesis of NIDDM. Cumulative evidence on the high prevalence of NIDDM in certain ethnic groups, the high concordance rate for the disease in monozygotic twins, familial aggregation, and familial transmission patterns suggests that the genetic component plays an important etiological role in the development of NIDDM. In genetically predisposed individuals, there is a slow progression from a normal state to hyperglycemia, largely due to a combination of insulin resistance and defects in insulin secretion. Although numerous candidate genes responsible for insulin resistance and for the defects in insulin secretion have been reported, no specific gene(s) accounting for the majority of cases of the common type of NIDDM has been identified. Considerable evidence indicates that environmental and other factors, including diet, stress, physical activity, obesity and aging, also play an important role in the development of the disease. In conclusion, the pathogenic process of NIDDM depends on a complex interaction between genetic and environmental factors.

Journal Article↗

PubMed1999

Prognostic significance of CD44 and nm23 expression in patients with stage II and stage IIIA gastric carcinoma.

BACKGROUND AND OBJECTIVES: Predicting the prognosis in gastric carcinoma patients with intermediate stages is difficult. We investigated the prognostic impacts of CD44 and nm23 expression in a homogeneous group of patients with stage II and IIIA gastric carcinoma who had undergone curative resections. METHODS: A total of 261 paraffin-embedded gastric carcinomas were stained with the monoclonal antibodies CD44 and nm23 using the labeled streptovidin biotin method. RESULTS: The expression of CD44 and nm23 was detected, respectively, in 31.0% (81/261) and 70.1% (183/261) of all tumors. There was no correlation between CD44 expression and clinicopathological variables. However, nm23 was more frequently expressed in older patients with differentiated adenocarcinoma. A significant difference in 5-year survival rates was found between patients with CD44-positive (43.2%) and CD44-negative tumors (63.4%), (P = 0.0018). However, there was no significant difference in 5-year survival rates between patients with nm23-positive (54.7%) and nm23-negative tumors (62.7%) (P = 0.2734). CONCLUSIONS: CD44 expression was a significant adverse prognostic factor in gastric carcinoma and may be a predictor of metastatic potential of the primary tumor. By contrast, immunohistochemical detection of nm23 expression was not a predictor of outcome of patients with gastric carcinoma.

Adult↗

PubMed1999

Effects of water extract of 1:1 mixture of Phellodendron cortex and Aralia cortex on polyol pathway and oxidative damage in lenses of diabetic rats.

Enhanced activity of the polyol pathway and oxidative damage have been implicated in the pathogenesis of diabetic cataract. We decided to investigate whether these changes in diabetic lenses could be prevented by the water extract of Phellodendron cortex and Aralia cortex (P55A). Aldose reductase activity was inhibited significantly by the treatment with P55A. Consequently, it caused a dramatic reduction in the high sorbitol contents observed in the lenses of diabetic rats. In addition, the greatly elevated content of thiobarbituric acid reactive substances (TBARS) and carbonylated protein in diabetic rats were reduced by P55A treatment. These results suggest that P55A extract exerts an antioxidant effect by reducing lipid peroxidation and protein carbonylation as well as having an inhibitory action against aldose reductase in the lenses of diabetic rats.

Aldehyde Reductase↗

PubMed1999

Structure and reaction mechanisms of multifunctional mitochondrial cytochrome bc1 complex.

The cytochrome bc1 complex from bovine heart mitochondria is a multi-functional enzyme complex. In addition to electron and proton transfer activity, the complex also processes an activatable peptidase activity and a superoxide generating activity. The crystal structure of the complex exists as a closely interacting functional dimer. There are 13 transmembrane helices in each monomer, eight of which belong to cytochrome b, and five of which belong to cytochrome c1, Rieske iron-sulfur protein (ISP), subunits 7, 10 and 11, one each. The distances of 21 A between bL heme and bH heme and of 27 A between bL heme and the iron-sulfur cluster (FeS), accommodate well the observed fast electron transfers between the involved redox centers. However, the distance of 31 A between heme c1 and FeS, makes it difficult to explain the high electron transfer rate between them. 3D structural analyses of the bc1 complexes co-crystallized with the Qu site inhibitors suggest that the extramembrane domain of the ISP may undergo substantial movement during the catalytic cycle of the complex. This suggestion is further supported by the decreased in the cytochrome bc1 complex activity and the increased in activation energy for mutants with increased rigidity in the neck region of ISP.

Animals↗

PubMed1999

Evaluation of biomarkers of environmental exposures: urinary haloacetic acids associated with ingestion of chlorinated drinking water.

A study was conducted to determine if DCAA and TCAA urinary excretion rates are valid biomarkers of chronic ingestion exposure to these disinfection by-products of chlorination of drinking water. Entire first morning urine voids, time-of-visit urine samples, and tap water samples were collected from 47 female subjects. In addition, a 48-h recall questionnaire was administered to determine the amounts and types of liquids ingested by each subject as well as other exposures that could lead to DCAA and TCAA urinary excretion. The TCAA excretion rate for the first morning urine samples was significantly correlated with the estimated 48-h TCAA ingestion exposure for 25 subjects whose ingestion exposures primarily occurred at home, while the DCAA excretion rate was not correlated with the DCAA ingestion exposure. Thus, urinary TCAA appears to be a valid biomarker of chronic ingestion exposure to TCAA from chlorinated water, while urinary DCAA is not. It is proposed that the difference in the biological half-lives between these two compounds is the rationale for this finding. The biological half-life of TCAA is longer than successive exposure intervals; thus TCAA accumulates until it reaches a steady state. The half-life of DCAA is shorter than successive exposure intervals; thus DCAA is almost completely metabolized following an exposure and is eliminated from the body. This study suggests that biological half-life, exposure interval, and sample collection interval should be considered in selecting biomarkers and designing studies to validate them.

Adolescent↗

PubMed1999

Role of O-acetyl-l-serine in the coordinated regulation of the expression of a soybean seed storage-protein gene by sulfur and nitrogen nutrition.

The composition of seed storage proteins is regulated by sulfur and nitrogen supplies. Under conditions of a low sulfur-to-nitrogen ratio, accumulation of the beta-subunit of beta-conglycinin, a sulfur-poor seed storage protein of soybean (Glycine max [L.] Merr.), is elevated, whereas that of glycinin, a sulfur-rich storage protein, is reduced. Using transgenic Arabidopsis thaliana [L.] Heynh., it was found that the promoter from the gene encoding the beta-subunit of beta-conglycinin up-regulates gene expression under sulfur deficiency and down-regulates gene expression under nitrogen deficiency. To obtain an insight into the metabolic control of this regulation, the concentrations of metabolites related to the sulfur assimilation pathway were determined. Among the metabolites, O-acetyl-l-serine (OAS), one of the precursors of cysteine biosynthesis, accumulated to higher levels under low-sulfur and high-nitrogen conditions in siliques of transgenic A. thaliana. The pattern of OAS accumulation in response to various levels of sulfur and nitrogen was similar to that of gene expression driven by the beta-subunit promoter. Elevated levels of OAS accumulation were also observed in soybean cotyledons cultured under sulfur deficiency. Moreover, OAS applied to in-vitro cultures of immature soybean cotyledons under normal sulfate conditions resulted in a high accumulation of the beta-subunit mRNA and protein, whereas the accumulation of glycinin was reduced. These changes were very similar to the responses observed under conditions of sulfur deficiency. Our results suggest that the level of free OAS mediates sulfur- and nitrogen-regulation of soybean seed storage-protein composition.

Antigens, Plant↗

PubMed1999

Germline origins in the human F9 gene: frequent G:C-->A:T mosaicism and increased mutations with advanced maternal age.

The factor IX gene (F9) is an advantageous system for analyzing recent spontaneous germline mutation in humans. Herein, the male:female ratio of mutation ("r") in F9 have been estimated by Bayesian analysis from 59 germline origin families. The overall "r" in F9 was estimated at 3.75. The "r"s varied with the type of mutation. The "r"s ranged from 6.65 and 6.10 for transitions at CpG and A:T to G:C transitions at non-CpG dinucleotides, respectively, to 0.57 and 0.42 for microdeletions/microinsertions and large deletions (>1 kb), respectively. The "r" for the two subtypes of non-CpG transitions differed (6.10 for A:T to G:C vs 0.80 for G:C to A:T). Somatic mosaicism was detected in 11% of the 45 origin individuals for whom the causative mutation was visualized directly by genomic sequencing of leukocyte DNA (estimated sensitivity of approximately one part in 20). Four of the five defined somatic mosaics had G:C to A:T transitions at non-CpG dinucleotides, hinting that this mutation subtype may occur commonly early in embryogenesis. The age at conception was analyzed for 41 US Caucasian families in which the age of the origin parent and the year of conception for the first carrier/hemophiliac were available. No evidence for a paternal age effect was seen. However, an advanced maternal age effect was observed (P=0.03) and was particularly prominent for transversions (average of the 79th percentile when maternal age was normalized for the year of conception). This suggests that an increased maternal age results in a higher rate of transmitted mutation, whereas the increased number of mitotic replications associated with advanced paternal age has little, if any, effect on the rate of transmitted mutation.

Adolescent↗

PubMed1999

Identification and phylogeny of novel human endogenous retroviral sequences belonging to the HERV-W family on the human X chromosome.

A new family (HERV-W) ofhuman endogenous retroviruses (HERVs) has recently been described that is related to MSRV (multiple sclerosis related retrovirus) sequences that have been identified in particles recovered from monocyte cultures from patients with multiple sclerosis. We investigated the pol fragment of HERV-W on the human X chromosome by the polymerase chain reaction (PCR) using a monochromosomal somatic cell hybrid DNA panel and compared these with related sequences in the genome database. We identified three novel sequences on the human X chromosome, HWXI, HWX3, and HWX5, which have a high degree of homology (88-98%) with the MSRV pol fragment and with seven other sequences. HWX5, like MSRV, has an uninterrupted open reading frame. Phylogenetic analysis showed HWX5 to be related to the HWX1, HWX3, and BAC clone B353C18 sequences with 91-93% homology. The ratio of synonymous to nonsynonymous substitutions indicated that negative selective pressure is acting on HWX5. Further studies on the structure and expression of this sequence are indicated.

Amino Acid Sequence↗

PubMed1999

Multiple intestinal ulcerations and perforations secondary to methicillin-resistant Staphylococcus aureus enteritis in infants.

PURPOSE: The aim of this study was to define a distinctive clinical entity of multiple intestinal ulcerations and perforations in infants. METHODS: Two infants underwent abdominal exploration for surgical abdomen and were noted to have multiple intestinal ulcerations and perforations. A peculiar and unique surgical finding, numerous transverse linear ulcerations scattered along the entire small intestine, prompted us to search for similar instances. Five similar cases were additionally identified by members of the Korean Association of Pediatric Surgeons. The clinical courses, the surgical findings, and the results of bacterial cultures were reviewed. As well, the tissues of resected intestines were examined histopathologically. RESULTS: The characteristics of this entity are as follows. (1) It usually occurs in infants who have been treated with broad-spectrum antibiotics. (2) Despite broad-spectrum antibiotic treatment, diarrhea and abdominal distension developed progressively and deteriorated. (3) Histological evaluation showed mucosal ulcers with neutrophil infiltration, submucosal microabscesses, and colonies of Gram-positive cocci. (4) Methicillin-resistant Staphylococcus aureus (MRSA) was the predominant organism cultured from the body fluid. (5) Only two cases, the completely resected one and the one immediately treated postoperatively with vancomycin, survived. CONCLUSIONS: This entity is caused by multiple intestinal ulcerations and perforations secondary to MRSA enteritis in infants. It has a high mortality rate because of its difficult diagnosis. However, early recognition of this entity can lead to successful treatment.

Anti-Bacterial Agents↗

PubMed1999

Patient-reported complications after cryoablation therapy for prostate cancer.

OBJECTIVES: To define the patient-reported complications after cryoablation therapy for prostate cancer and to compare these results to previously published patient-reported complications for radical prostatectomy and external beam irradiation. METHODS: A questionnaire similar to previously published patient-reported complication studies was sent to the first 290 patients treated by cryoablation therapy at our institution. The questionnaire was returned by 267 patients. Forty-four patients were excluded from analysis because of prior irradiation, transurethral prostatectomy, or cryoablation, resulting in a study group of 223 patients. RESULTS: Of the 208 patients with good urinary control preoperatively, 9 (4.3%) patients used incontinence pads after cryoablation. Seven of the 8 patients who used one pad daily reported leakage of only a few drops. Impotency, defined as an inability to obtain erections adequate for vaginal penetration, occurred in 85% of men who were potent preoperatively. Urethrorectal fistula occurred in 1 patient (0.4%). Bladder outlet obstruction caused by stricture or sloughed necrotic prostatic tissue required dilation or transurethral resection in 10% of patients. Scrotal swelling, penile tingling, and pelvic pain occurred in 18%, 15%, and 12% of patients, respectively; typically, these resolved spontaneously within 3 months. CONCLUSIONS: Patient-reported complications for cryoablation compared favorably to those reported for radical prostatectomy and external beam irradiation. Patient satisfaction was high; 96% of patients reported that they would choose cryosurgery as a treatment option again.

Aged↗

PubMed1999

Mast cells express connexins on their cytoplasmic membrane.

BACKGROUND: Because of the close association between mast cells and fibroblasts in the microenvironment and the importance of connexins (Cxs) in fibroblast communication with other cells, we hypothesized that mast cells also express Cxs, allowing them to similarly communicate with other cells through gap junctions. OBJECTIVES: We sought to identify the expression of Cxs (particularly Cx43, Cx32, and Cx26) by murine mast cells. METHODS: The expression of Cxs was studied by RT-PCR, Northern blot analysis, Western blot analysis, flow cytometry, and confocal laser scanning microscopy. RESULTS: In this report we demonstrate that murine bone marrow cultured mast cells and the growth factor-independent murine mast cell line C57, express Cx43 and Cx32 as assessed by RT-PCR, Northern blot analysis, Western blot analysis, and flow cytometry, but do not express Cx26. We also show, by confocal laser scanning microscopy, that Cx43 localizes to the cytoplasmic membrane of mast cells in a pattern similar to that seen in fibroblasts. CONCLUSIONS: Mast cells express Cx43 and Cx32, and Cx43 is associated with the cytoplasmic membrane, suggesting that mast cells have the potential to communicate with other cells in their microenvironment in part through gap junctions.

Animals↗

PubMed1999

Respiratory depression after intravenous administration of delta-selective opioid peptide analogs.

We compared the effects of three micro-(DAMGO, DALDA, TNPO) and three delta-(DPDPE, DELT, SNC-80) opioid agonists on arterial blood gas after IV administration in awake sheep. None of the mu agonists altered pO2, pCO2 or pH. All three mu agonists decreased pO2 increased pCO2 and decreased pO2, and this effect was not sensitive to naloxone or TIPPpsi, a delta-antagonist, suggesting that it is not mediated by beta-opioid receptors. When administered to pregnant animals, there were significant changes in fetal pCO2 and pH. It may be possible to develop delta-selective opioid agonists which do not produce respiratory depression.

Analgesics↗

PubMed1999

Variability in ultrasonic measurements of arterial stiffness in the Atherosclerosis Risk in Communities study.

Arterial stiffness is emerging as an important risk marker for cardiovascular disease. Ultrasound-based measurements of arterial stiffness are in use by several large epidemiological studies. The reliability of ultrasonic measurements of arterial stiffness was assessed as part of one of these, the Atherosclerosis Risk in Communities (ARIC) study. ARIC, a prospective, four-center epidemiological study, used B-mode ultrasound with an electronic tracking device to measure arterial stiffness of the carotid artery. Oscillometric blood pressure measures were obtained before and after the arterial wall tracking. Measurement variability was estimated in 36 volunteers who were scanned at three visits conducted at 7- to 14-day intervals. Between- and within-person components of variation were estimated for arterial diameter and blood-pressure measurements. The correlation (R) between repeated measurements for pulse pressure, the percent change in arterial diameter (strain), and the percent and absolute change in the arterial area were 0.69, 0.67, 0.66 and 0.81, respectively. The R for the stress-strain elastic modulus (Ep), arterial distensibility, and arterial compliance were 0.66, 0.67, and 0.77, respectively. The R for the pressure-adjusted diameter change (i.e., diameter change adjusted for diastolic and pulse pressures) was 0.75. In summary, the ultrasonic measurements of arterial stiffness employed in the ARIC study demonstrate excellent short-term repeatability, demonstrating their utility in field settings.

Arteriosclerosis↗

PubMed1999

Lateralizing value of the Wada memory test in non-Western patients with temporal lobe epilepsy.

The Wada memory test measures a psychological construct (i.e. memory), which is widely acknowledged to be under the influence of a vast array of moderating variables including culture. Thus, the lateralizing value of the Wada memory test for epileptogenic foci may potentially differ for Western versus non-Western patients with temporal lobe epilepsy (TLE). In the present study, the lateralizing value of the Wada memory test was investigated in 17 Korean patients with medically intractable TLE who were post-operatively seizure-free. The Wada memory stimuli were composed of eight drawings of common objects, animals, and fruits. A clinical criterion of at least 2 points difference between left and right injections correctly classified 14 patients (82%) into left and right TLE groups, with only one patient (6%) falsely classified. This diagnostic accuracy is at least as high as that reported for Western TLE patients. These results indicate that whatever culture-specific factors Korean TLE patients may bring to the Wada memory test, they do not significantly reduce the lateralizing value of the test.

Adult↗

PubMed1999

Metabolism of genistein by rat and human cytochrome P450s.

The metabolism of genistein (4',5,7-trihydroxyisoflavone), a phytoestrogen derived from soy products, was investigated using rat and human liver microsomes and recombinant human cytochrome P450 enzymes. Metabolism of genistein by microsomes obtained from rats treated with pyridine, phenobarbital, beta-naphthoflavone, isosafrole, pregnenolone-16alpha-carbonitrile, or 3-methylcholanthrene resulted in very different product profiles consisting of five different NADPH- and time-dependent metabolites as observed by HPLC reverse-phase analysis at 260 nm. The metabolism of genistein was also investigated with recombinant human cytochrome P450 1A1, 1A2, 1B1, 2B6, 2C8, 2E1, or 3A4. P450s 1A1, 1A2, 1B1, and 2E1 metabolized genistein to form predominantly one product (peak 3) with smaller amounts of peaks 1 and 2. P450 3A4 produced two different products (peaks 4 and 5). Product peaks 1-3 eluted off the HPLC column prior to the parent compound genistein, and the UV/vis spectra, GC/MS, and ESI/MS/MS analyses support the conclusion that these products result from hydroxylation of genistein. The product peak 3 has been identified by tandem mass spectrometry as 3',4',5, 7-tetrahydroxyisoflavone, also known as orobol, and peaks 1 and 2 appear to be hydroxylated at position 6 or 8.

Animals↗