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Biomedical subjects

H Kim

Publications and source records attributed to H Kim.

At least 19 recordsLinked to original sources
PubMed2007

Human amniotic fluid-derived stem cells have characteristics of multipotent stem cells.

OBJECTIVES: To characterize mesenchymal stem cell-like cells isolated from human amniotic fluid for a new source of therapeutic cells. MATERIALS: Fibroblastoid-type cells obtained from amniotic fluid at the time of birth. METHODS: The ability of ex vivo expansion was investigated until senescence, and stem cell-like characteristics were analyzed by examining differentiation potential, messenger RNA expression and immunophenotypes. RESULTS AND CONCLUSIONS: A morphologically homogenous population of fibroblastoid-type (HAFFTs) cells, similar to mesenchymal stem cells from bone marrow (BM-MSCs), was obtained at the third passage. The cells became senescent after 27 passages over a period of 8 months while undergoing 66 population doublings. Under appropriate culture conditions, by the 8th passage they differentiated into adipocytes, osteocytes, chondrocytes and neuronal cells, as revealed by oil red O, von Kossa, Alcian blue and anti-NeuN antibody staining, respectively. Immunophenotype analyses at the 17th passage demonstrated the presence of TRA-1-60; SSEA-3 and-4; collagen types I, II, III, IV and XII; fibronectin; alpha-SMA; vimentin; desmin; CK18; CD44; CD54; CD106; FSP; vWF; CD31; and HLA ABC. Reverse transcriptase-polymerase chain reaction analysis of the HAFFTs from passages 6-20 showed consistent expression of Rex-1, SCF, GATA-4, vimentin, CK18, FGF-5 and HLA ABC genes. Oct-4 gene expression was observed up to the 19th passage but not at the 20th passage. HAFFTs showed telomerase activity at the 5th passage with a decreased level by the 21st passage. Interestingly, BMP-4, AFP, nestin and HNF-4alpha genes showed differential gene expression during ex vivo expansion. Taken together, these observations suggest that HAFFTs are pluripotent stem cells that are less differentiated than BM-MSCs, and that their gene expression profiles vary with passage number during ex vivo expansion.

Amniotic Fluid↗
PubMed2006

DNA repair Ku proteins in gastric cancer cells and pancreatic acinar cells.

The DNA repair protein Ku acts as a heterodimer of Ku70 and Ku80 that binds to the DNA ends, nicks, or single-to-double-strand transition. It has a crucial role for DNA double-strand-break repair. Either Ku70 or Ku80 itself may have a unique function that is independent of the other Ku subunit. In this review, the role of Ku on cell proliferation and apoptosis will be discussed. Ku acts as a regulator of transcription by interacting with the recombination signal binding protein Jkappa and the NF-kappaB p50 homodimer to up-regulate p50 expression, which may regulate the proliferation of gastric cancer cells. Both Ku70 and Ku80 expressions are mediated by constitutively activated NF-kappaB and constitutively expressed cyclooxygenase-2 in gastric cancer cells, which may be related to gastric cell proliferation and carcinogenesis. In addition, nuclear loss of Ku may underlie the mechanism of apoptosis in pancreatic acinar cells after oxidative stress.

Animals↗
PubMed2006

Nicotinamide reverses neurological and neurovascular deficits in streptozotocin diabetic rats.

In diabetes, activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is an important effector of oxidative-nitrosative injury, which contributes to the development of experimental diabetic peripheral neuropathy (DPN). However, the potential toxicity of complete PARP inhibition necessitates the utilization of weaker PARP inhibitors with additional therapeutic properties. Nicotinamide (vitamin B3) is a weak PARP inhibitor, antioxidant, and calcium modulator and can improve energy status and inhibit cell death in ischemic tissues. We report the dose-dependent effects of nicotinamide in an established model of early DPN. Control and streptozotocin-diabetic rats were treated with 200 to 400 mg/kg/day nicotinamide (i.p.) for 2 weeks after 2 weeks of untreated diabetes. Sciatic endoneurial nutritive blood flow was measured by microelectrode polarography and hydrogen clearance, and sciatic motor and hind-limb digital sensory nerve conduction velocities and thermal and mechanical algesia were measured by standard electrophysiological and behavioral tests. Malondialdehyde plus 4-hydroxyalkenal concentration in the sciatic nerve and amino acid-(4)-hydroxynonenal adduct and poly(ADP-ribosyl)ated protein expression in human Schwann cells were assessed by a colorimetric method with N-methyl-2-phenyl indole and Western blot analysis, respectively. Nicotinamide corrected increased sciatic nerve lipid peroxidation in concert with nerve perfusion deficits and dose-dependently attenuated nerve conduction slowing, as well as mechanical and thermal hyperalgesia. Nicotinamide (25 mM) prevented high (30 mM) glucose-induced overexpression of amino acid-(4)-hydroxynonenal adducts and poly(ADP-ribosyl)ated proteins in human Schwann cells. In conclusion, nicotinamide deserves consideration as an attractive, nontoxic therapy for the treatment of DPN.

Animals↗
PubMed2006

Effects of a combined alendronate and calcitriol agent (Maxmarvil) on bone metabolism in Korean postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study.

INTRODUCTION: A randomized, double-blind, prospective, 24-week clinical trial was performed to evaluate the effects of a combinative agent, Maxmarvil, of calcitriol (0.5 mug) and alendronate (5 mg) on bone metabolism in postmenopausal women. METHODS: A total of 217 postmenopausal women with osteoporosis were enrolled; 199 patients were randomly assigned to one of two treatment groups (Maxmarvil group or alfacalcidol group). None of the patients were vitamin-D-deficient, as assessed by serum 25-hydroxyvitamin D (25(OH)D), nor had they received any drugs affecting bone metabolism before enrollment. Bone mineral densities (BMD) of L1-L4 and the femur were measured by dual-energy X-ray absorptiometry (DXA) at the initial assessment and after 6 months of treatment. Serum biochemical assays, including serum calcium, 24-h urinary calcium excretion, and bone turnover markers (both bone-specific alkaline phosphatase [bsALP] and urine N-telopeptide [NTx]), were performed at the baseline and after 3 and 6 months of treatment. RESULTS: In the Maxmarvil group, the BMD of the lumbar spine increased up to 2.42+/-0.5% from the baseline after 6 months (p<0.05). On the other hand, the change in BMD in the alfacalcidol group was 0.28+/-0.5% after 6 months. There was no significant difference in femoral BMD between the two groups. The levels of bsALP and NTx were significantly lower in the Maxmarvil group than in the alfacalcidol group (-22.04+/-3.9% vs. -11.42+/-2.8% [p<0.05] and -25.46+/-5.2% vs. 1.24+/-6.2% [p<0.001], respectively). Interestingly, there was a significantly smaller amount of 24-h urinary calcium in the Maxmarvil group (p<0.05). CONCLUSIONS: Our study demonstrates that a combination of calcitriol and alendronate is quite effective in preventing bone loss, with the advantage of lesser hypercalciuric effect of calcitriol in the postmenopausal osteoporotic women.

Alendronate↗
PubMed2006

Use of silicone stents for the management of post-tuberculosis tracheobronchial stenosis.

The role of bronchoscopic management in post-tuberculosis tracheobronchial stenosis is not well defined. To investigate the role of bronchoscopic intervention, including silicone stenting, in the management of post-tuberculosis tracheobronchial stenosis, the current retrospective study was conducted at a tertiary referral hospital. Under rigid bronchoscopy, 80 patients underwent ballooning, neodymium-yttrium aluminium garnet laser resection and/or bougienation as first-line methods of airway dilatation between January 2000 and December 2003 inclusive, and were followed for a median of 41 months. Silicone stents were required in 75 out of 80 (94%) patients to maintain airway patency. Bronchoscopic intervention provided immediate symptomatic relief and improved lung function in 88% of the patients. After airway stabilisation, stents were removed successfully in 49 out of 75 (65%) patients at a median of 14 months post-insertion. Three patients out of 75 (4%) eventually underwent surgical management. Acute complications included: excessive bleeding (n = 1); pneumothorax (n = 5); and pneumomediastinum without mortality (n = 2). Stent-related late complications, such as migration (51%), granuloma formation (49%), mucostasis (19%) and re-stenosis (40%), were controllable during a median follow-up of 41 months. In conclusion, bronchoscopic intervention, including silicone stenting, could be a useful and safe method for treating post-tuberculosis tracheobronchial stenosis.

Adolescent↗
PubMed2006

Repeated brief epileptic seizures by pentylenetetrazole cause neurodegeneration and promote neurogenesis in discrete brain regions of freely moving adult rats.

Recurrent epileptic seizures are known to provoke various forms of cellular reorganization in the brains of humans and experimental animals. However, little is known about the mechanism of neuronal cell death resulting from epileptic seizures elicited by GABA antagonists. In the present study, we explored the effect on the central nervous systems of freely moving adult rats, of repeated brief epileptic seizures induced by systemic injection of pentylenetetrazole, a GABA-A receptor antagonist. Starting with minor convulsions, repeated epileptic seizures elicited a progressive increase in seizure severity, culminating in the fully kindled state. Histological examination showed that the epileptic seizures caused overt neuronal cell death in the limbic system, including the hippocampus and amygdala, and its adjoining cortex. During the recurrent epileptic seizures, neurogenesis occurred in the subgranular zone of the hippocampus, the subventricular zone of the lateral ventricle, and the amygdala. This type of pentylenetetrazole-induced neurogenesis was seen at an early stage of epileptogenesis in some regions in which massive cell loss was not evident. This suggests that neurogenesis is not a secondary consequence of neuronal cell death, but rather an independent effect of recurrent epileptic seizures.

Animals↗
PubMed2006

Concurrent delivery of GM-CSF and B7-1 using an oncolytic adenovirus elicits potent antitumor effect.

Oncolytic adenoviral vectors are currently being developed as biologic anticancer agents. Coupling the lytic function of an oncolytic adenovirus (Ad) with its ability as a transgene delivery system represents a powerful extension of this methodology. A clear advantage is the amplification of a therapeutic gene, as replicating vectors would be able to infect and deliver the gene of interest to neighboring cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of the most potent stimulators of a specific and long-lasting antitumor immunity and its important role in the maturation of antigen-presenting cells to induce T-cell activation has been well documented. Similarly, the B7 family has also been shown to play an integral role in mediating an antitumor response. Most tumor cells, however, lack the expression of these costimulatory molecules on their surface, thus escaping immune system recognition. To increase the antitumor effect of an oncolytic Ad, we have generated an E1B 55 kDa-deleted oncolytic adenoviral vector, YKL-GB, that expresses both GM-CSF and B7-1. The therapeutic efficacy of YKL-GB Ad was evaluated in immunocompetent mice bearing murine melanoma B16-F10 tumors. Significant inhibition of tumor growth was seen in mice treated with YKL-GB compared to those treated with the analogous vector, YKL-1. Moreover, YKL-GB oncolytic Ad demonstrated enhanced antitumor activity and higher incidences of tumor regression compared to a replication-incompetent Ad, dl-GB, which coexpresses GM-CSF and B7-1. Localized GM-CSF and B7-1 gene transfer also conferred long-lasting immunity against a tumor re-challenge. To establish that the observed antitumor effect is associated with the generation of a tumor-specific immune response, we carried out interferon-gamma enzyme-linked immune spot assay. We observed that YKL-GB induced significantly higher immune cell activation than YKL-1. Furthermore, immunohistochemical studies demonstrated robust dendritic cells and CD4(+)/CD8(+) T-cell infiltration in these mice compared to the YKL-1-treated groups. In agreement with these results, splenocytes from tumor-bearing mice treated with YKL-GB expressed high levels of the costimulatory and activation molecules. These findings demonstrate the effectiveness of enhancing the immune response against tumors with an oncolytic Ad expressing both GM-CSF and B7-1 and provide a potential therapeutic strategy for the management of neoplasia.

Adenoviridae↗
PubMed2006

Two cases of citrullinaemia presenting with stroke.

Urea cycle disorders are known to be unusual causes of stroke. We report two infant cases of citrullinaemia that both initially presented with a stroke and suggest that urea cycle disorders should be included in the differential diagnosis of unexplained stroke during infancy and childhood.

Argininosuccinate Synthase↗
PubMed2006

Benign localized fibrous tumour of the pleura: CT features with histopathological correlations.

AIM: To assess the CT features of benign localized fibrous tumour of the pleura, with histopathological correlations. MATERIALS AND METHODS: CT and histopathological findings of 18 patients with surgically resected benign localized fibrous tumour of the pleura were retrospectively assessed. RESULTS: Tumours were pleura or fissure based, semilunar, lentiform or oval in shape, classified according to their homogeneous, slightly heterogeneous or heterogeneous enhancement pattern. Of the 18 tumours, 5 (28%) demonstrated > or = 55 HU increment or higher attenuation than muscles on contrast-enhanced CT, and histopathologically showed a haemangiopericytoma-like pattern with rich vascularity. CONCLUSION: CT analysis of the shape of a mass and the enhancement pattern can be helpful in the diagnosis of benign localized fibrous tumour of the pleura.

Adult↗
PubMed2006

Routine screening for the functional asymmetry of potential kidney donors.

The functional capacity of each kidney of a healthy donor may change under the influence of genetic and environmental factors. An assumption that the donor kidneys show equal function is not always true. As part of the pre-nephrectomy evaluation of potential donors, radioisotope renal scintigraphy using technetium-99m diethylenetriaminepentaacetic acid (99mTcDTPA) was routinely included to evaluate renal functional asymmetry of undetermined etiology. The functional ratios of each kidney using 99mTcDTPA as well as serum creatinine (Scr) and creatinine clearance (Ccr) in a 24-hour urine were measured and calculated from a hundred donors. The left kidneys showed greater function (51.67%-53.35% under 95% confidence interval [CI]) and the average left versus right ratio was 52.5 versus 47.5. The average fraction of Ccr of left kidneys was 57.8 mL/min/1.73 m +/- 10.99 compared with right kidneys at 52.6 mL/min/1.73 m +/- 11.63. Seventy-three healthy volunteers donated their left kidneys, and 27, their right kidney. The average fraction of Ccr of the donated kidneys was 55.9 mL/min/1.73 m +/- 11.78 compared with that of the remnant kidneys (54.5 mL/min/1.73 m +/- 11.39). After kidney donation, the Scr of the donors increased from 0.85 mg/dL +/- 0.17 to 1.33 mg/dL +/- 0.27. The average postnephrectomy Ccr was 68.0 mL/min/1.73 m +/- 14.29. Even though the Ccr after kidney donation was higher than that of the remnant kidney estimated before the donation, one must pay attention to possible functional kidney asymmetry to select the nephrectomy site.

Humans↗
PubMed2006

Fractional creatinine clearance of the donated kidney using Cockcroft-Gault formula as a predictor of graft function after living donor transplantation.

To prevent hyperfiltration of the renal allograft, it is important to initially provide adequate functioning nephrons to meet the metabolic demands of a recipient. During the preoperative evaluation of a potential kidney donor, it is necessary to estimate the renal function of donated kidney compared with the metabolic needs of the recipient. The functional ratio of each kidney was measured using technetium-99m diethylenetriaminepentaacetic acid. The serum creatinine (Scr, mg/dL) and estimated creatinine clearance (Ccr, mL/min/1.73 m(2)) using the Cockcroft-Gault formula were measured and calculated in 82 donors. We excluded recipients who had an episode of rejection, and followed all recipients for more than 6 months posttransplantation. The average functional proportion of the donated kidney was 50.5% +/- 4.7% of the total Ccr 83.4 +/- 18.3 of donors. The Scr of recipients at 1, 3, 6, and 9 months posttransplantation were significantly (P < .05) correlated with the fractional Ccr of the donated kidney; however, Scr at 1 year was not correlated (P = .307). Furthermore, the Ccr of the recipient at 1, 3, and 6 months posttransplantation were significantly (P < .05) correlated with the fractional Ccr of the donated kidney; however, the Ccr at 9 months and 1 year were not correlated (P = .094 and .141, respectively). The Scr and Ccr of recipients within 6 months after transplantation may depend on the functional mass of the donated kidney, which should be estimated prior to kidney donation and compared with the metabolic demands of the potential recipient.

Creatinine↗
PubMed2006

Effect of basiliximab on renal allograft rejection within 1 year after transplantation.

Basiliximab is widely used in clinical practice for initial immunosuppressive treatment of renal transplant recipients, seeking to reduce the incidence of acute rejection episodes without adverse events. This retrospective study included 123 renal allograft recipients transplanted at a single center. All were followed for longer than 1 year after transplantation and treated with calcineurin inhibitor and steroid (methylprednisolone) for prophylactic immunosuppression, but basiliximab and mycophenolate mofetil were optional. We compared the outcomes of renal transplant recipients who were versus treated were not with basiliximab as initial immunosuppressive therapy. Basiliximab was used for initial immunosuppression in 42 patients. Their maintenance immunosuppressive treatment included triple (n = 44) or double (n = 79) regimens, including a calcineurin inhibitor (cyclosporine [n = 87] or tacrolimus [n = 36]), methylprednisolone with or without mycophenolate mofetil. Twenty-six (21.1%) patients had a rejection episode within 1 year after transplantation and 22 (17.9%) had infections. Within the first year after transplantation the patients who were treated with basiliximab showed fewer rejection episodes (n = 6, 14.3%) than the patients without this therapy (n = 20, 24.7%), which was not statistically significant (P = .245). However, basiliximab significantly affected the occurrence of rejection episodes among the double immunosuppressive regimen group (P = .006), but not the triple regimen group (P = .098) without an impact on infection episodes (P value of double, triple = .291, .414) within 1 year after transplantation. We concluded that basiliximab was more useful for the recipients treated with double immunosuppression with a calcineurin inhibitor and steroid than for those on a triple regimen including mycophenolate mofetil.

Adult↗
PubMed2006

Early lymphocyte recovery predicts longer survival after autologous peripheral blood stem cell transplantation in multiple myeloma.

To understand the prognostic value of lymphocyte recovery after autologous peripheral blood stem cell transplantation (APBSCT), we performed a retrospective study of 59 newly diagnosed multiple myeloma (MM) patients who underwent frontline APBSCT. Conditioning regimens were melphalan 100 mg/m(2) for 2 days. Following APBSCT, all patients showed complete or partial response. Median follow-up time was 29.57 months and median recovery of absolute lymphocyte count (ALC) > or =1000/mm(3) was 23 days. Univariate analysis revealed that significant predictors of overall survival (OS) included bone marrow (BM) plasma cells < or =40% at diagnosis (P=0.0243) and recovery of ALC > or =1000/mm(3) by day +23 (P=0.0156). Positive predictors for progression-free survival (PFS) were BM plasma cells < or =40% at diagnosis (P=0.0134) and recovery of ALC > or =1000/mm(3) by day +23 (P=0.0243). Absolute neutrophil count > or =1000/mm(3) on day +12 was marginally significant for OS and PFS (P=0.0821 and P=0.1153, respectively). Multivariate analysis showed that ALC > or =1000/mm(3) on day +23 independently predicted OS (P=0.031) and prolonged PFS (P=0.011), and that serum beta2-microglobulin was marginally significant for prolonged OS (P=0.066). In conclusion, ALC recovery was an independent predictor of both OS and PFS in MM.

Adult↗
PubMed2006

Risk score model for fatal intracranial hemorrhage in acute leukemia.

To build a risk score (RS) model of fatal intracranial hemorrhage (FICH) in patients with acute leukemia, we retrospectively assessed risk factors in 792 patients newly diagnosed with acute leukemia, 41 of whom had analyzable FICH. We found that female gender (relative risk (RR) = 5.234, P<0.001), acute promyelocytic leukemia (RR = 4.057, P = 0.003), leukocytosis (RR = 3.301, P = 0.004), thrombocytopenia (RR = 3.283, P = 0.005) and prolonged prothrombin time (RR = 3.291, P = 0.016) were significantly associated with occurrence of FICH in multivariate analysis. To calculate RS for FICH, one point was assigned for each risk factor, making the RS between 0 and 5. The RS model segregated patients into three prognostic groups: a low-risk group (LRG) for RS of 0 or 1; an intermediate-risk group (IRG) for RS of 2 or 3; and a high-risk group (HRG) for RS of 4 or 5. Expectation of FICH was well correlated with risk groups (all P-values < 0.001). Overall survival was significantly shorter in the HRG compared with the LRG. The RS model we constructed to predict the occurrence of FICH will be verified through prospective studies.

Acute Disease↗
PubMed2006

In vitro endothelial potential of human UC blood-derived mesenchymal stem cells.

BACKGROUND: Human mesenchymal stem cells (MSC) possess powerful ex vivo expansion and versatile differentiation potential, placing themselves at the forefront of the field of stem cell-based therapy and transplantation. Of high clinical relevance is the endothelial differentiation potential of MSC, which can be used to treat various forms of ischemic vascular disease. METHODS: We investigated whether human umbilical cord blood (UCB)-derived MSC are able to differentiate in vitro along an endothelial lineage, by using flow cytometry, RT-PCR and immunofluorescence analyzes, as well as an Ab array method. RESULTS: When the cells were incubated for up to 3 weeks in the presence of VEGF, EGF and hydrocortisone, they began to express a variety of endothelial lineage surface markers, such as Flk-1, Flt-1, VE-Cadherin, vWF, VCAM-1, Tie-1 and Tie-2, and to secrete a specific set of cytokines. Differentiated cells were also found to be able to uptake low-density lipoprotein and form a tubular network structure. DISCUSSION: These observations have led us to conclude that UCB-derived MSC retain endothelial potential that is suitable for basic and clinical studies aimed at the development of vasculature-directed regenerative medicine.

Antigens, CD↗
PubMed2006

Subcutaneous hyalohyphomycosis due to Cephalotheca foveolata in an immunocompetent host.

We report the first case of subcutaneous hyalohyphomycosis caused by the genus Cephalotheca, which has not been reported to cause human infection. A 67-year-old immunocompetent farmer presented with a 10-year history of verrucous erythematous plaques on the right foot dorsum, great toe, heel and sole. Histopathology of the lesions revealed chronic granulomatous inflammation with numerous nonpigmented fungal spores in the dermis. Cultures of biopsy specimens on Sabouraud's dextrose agar for 2 weeks developed into yellowish brown, velvety colonies that subsequently turned black after 8 weeks because of the production of black cleistothecia indicating the teleomorph. On the basis of mycological features, scanning electron microscopic morphology and molecular analysis data, a new species of Cephalotheca was identified and designated Cephalotheca foveolata. Because there was no response to the antifungal agents administered, the patient was successfully treated by surgical excision with skin graft.

Aged↗
PubMed2006

PKD2 gene mutation analysis in Korean autosomal dominant polycystic kidney disease patients using two-dimensional gene scanning.

Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous and is caused by mutations in the PKD1 or PKD2 genes. ADPKD caused by PKD2 mutations is characterized by a longer survival and a later onset of end-stage renal disease than ADPKD caused by PKD1 mutations. PKD2 encodes a 2.9-kb messenger RNA and is derived from 15 exons. Two-dimensional gene scanning (TDGS) is more efficient in detecting mutations in genes such as PKD2 because it can scan the whole coding regions simultaneously. In order to determine the prevalence of Korean PKD2 patients, all the coding sequences of PKD2 were screened using TDGS and direct sequencing in 46 randomly selected ADPKD patients (group 1). Another 45 ADPKD patients (group 2), who were presumed to be PKD2 patients, were screened in order to identify the type of mutation in the Korean PKD2 patients. Eight novel different mutations and three known mutations in the PKD2 gene were detected in 17 patients: 6 patients (13.0%) in group 1 and 11 patients (24.4%) in group 2. Considering the sensitivity of TDGS, the prevalence of PKD2 in Korean population might be greater than 18.6%. Both known and novel mutations were identified by TDGS in Korean PKD2 patients. Overall, these results showed that TDGS might be useful for diagnosing PKD2.

Chromosome Mapping↗