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Biomedical subjects

K K Park

Publications and source records attributed to K K Park.

At least 19 recordsLinked to original sources
PubMed2004

BK virus infection in kidney transplant recipients.

INTRODUCTION: Nephropathy associated with the polyomavirus type BK virus (BKV) has emerged as a cause of allograft failure linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil (MMF). The outcome in BKV nephropathy is generally unfavorable, namely 50% of patients lose graft function. We herein report nine cases of BKV nephropathy after kidney transplantation. METHODS: From October 1998 to May 2003, 138 of 169 consecutive kidney transplant patients received tacrolimus-based immunosuppression, and 31 received cyclosporine-based immunosuppression. Additionally, 88.2% of the patients received mycophenolate mofetil (MMF). The diagnosis of BK infection was made by the presence of decoy cells in the urine and by allograft biopsy. RESULTS: There were nine cases of BKV nephropathy in kidney transplant recipients, an incidence of 5.3%. All patients with BKV nephropathy received tacrolimus, MMF, and steroids. The median time to diagnosis of BKV infection was 7.8 months after transplantation. All patients experienced an elevated serum creatinine, which stabilized or decreased in seven patients with altered or decreased immunosuppression. After a mean follow-up of 11.1 months, 2 (22.2%) of nine patients lost the graft. CONCLUSION: Because BKV nephropathy is a rare but serious complication after kidney transplantation, it should be included in the clinical differential of transplant dysfunction. In the absence of documented antiviral treatment, early diagnosis and judicious use of immunosuppressive agents is indicated to minimize the occurrence of BKV infection.

Adult↗
PubMed2004

Ultrastructural evaluation of the protective effect of nitroglycerin in preservation-reperfusion injury of rat lungs.

AIM OF STUDY: Nitric oxide (NO) has been reported as a favorable protective supplement in donor lung preservation, but related ultrastructural studies are rare in the literature. This study was performed to assess the ultrastructural changes and to evaluate the protective effect of NO as donor nitroglycerin (NTG) treatment of ischemia-reperfusion injury in rat lungs. MATERIALS AND METHODS: Fifteen Sprague-Dawley rats weighing 300 to 350 g were used in this study. The NTG group (n = 5) used intravenous administration followed by mixture in the University of Wisconsin (UW) solution. For the non-NTG group (n = 5), we injected the same amount of normal saline intravenously followed by admixture in the UW solution. The heart-lung blocks were removed, weighed, and kept in UW solution for 24 hours at 10 degrees C. Reperfusion using human blood diluted in Krebs-Hensleit solution was done for 60 minutes. For the control group (n = 5), we injected the same amount of normal saline intravenously, and removed the lungs with no preservation and reperfusion procedures. RESULTS: The non-NTG group showed multiple patchy areas of alveolar collapse with marked swelling and destruction of type I epithelial cells, loss of type II cell surfactant granules, endothelial swelling and papillary projection, interstitial edema, and alveolar macrophages with active phagocytosis of the destroyed materials. The NTG group showed similar ultrastructural changes, but in a lesser severity compared with the non-NTG group. CONCLUSION: Administration of the NTG reduced the ischemia-reperfusion injury in the rat donor lungs. Ultrastructural examination was an effective tool to evaluate the protective effect of NTG in ischemia-reperfusion procedures of donor lungs.

Animals↗
PubMed2004

A case of primary cutaneous aspergillosis in a renal transplant recipient.

UNLABELLED: Opportunistic fungal infections are life-threatening complications which are a major cause of morbidity and mortality in immunocompromized hosts such as those who have undergone organ transplantation. Aspergillosis comprises a spectrum of disease caused by a ubiquitous saprophytic mold. Invasive aspergillus is a serious life-threatening complication in immunocompromised hosts. Primary cutaneous aspergillosis occurs relatively less frequently and is poorly characterized. We report a case of cutaneous aspergillosis in a 51-year-old renal transplant recipient, which was successfully treated with local excision and concomitant antifungal therapy. CASE: A 51-year-old male renal transplant recipient presented with cutaneous nodules on the dorsum of the right hand. He underwent renal transplantation for end-stage renal disease due to adult dominant polycystic kidney disease (ADPKD) 3 years prior. Initially he suffered an acute rejection episode that was treated with steroid pulse and OKT3 therapy. Eventually he was stabilized on a combination of tacrolimus, prednisone, and mycophenolate mofetil. Three years after transplantation, he developed painless multiple (largest one 5 x 3 cm sized) nodules on the dorsum of his right hand. He was afebrile with no systemic symptoms. A skin biopsy showed a dense solid infiltration of giant cells, histiocytes, and lymphoplasma cells admixed with intra- and extracellular fungal hyphae and spores. The hyphae were septate and acute angle branching, which was consistent with aspergillosis. Oral itraconazole 200 mg/d for 5 weeks was ineffective. Treatment with liposomal amphotericin B for 4 weeks was initiated and MMF was discontinued. The medication was well tolerated with no hepatotoxic effects. Although new lesions did not appear, existing ones did not significantly improve after 4 weeks of treatment. Therefore, most lesions were excised surgically and liposomal amphotericin B continued for 2 weeks followed by treatment with oral fluconazole for 2 months. Ten moths later there was no evidence of recurrence.

Antifungal Agents↗
PubMed2004

Transcription factor decoy for AP-1 reduces mesangial cell proliferation and extracellular matrix production in vitro and in vivo.

Diabetic nephropathy is characterized by an expansion of glomerular mesangium, caused by mesangial cell proliferation and excessive accumulation of extracellular matrix (ECM) proteins, which eventually leads to glomerulosclerosis and renal failure. Activator protein-1 (AP-1), a transcription factor, is implicated in the transcriptional regulation of a wide range of genes participating in cell proliferation and ECM production. This investigation was undertaken to test the hypothesis that AP-1 plays an important role in ECM gene expression, and to develop a molecular therapeutic strategy based on decoy oligodeoxynucleotides (ODN). In this report, we show that transfection with AP-1 decoy ODN strongly inhibits high glucose- and angiotensin II-induced cell proliferation and expression of ECM genes in cultured mesangial cells in vitro. Administration of AP-1 decoy ODN into streptozotocin-induced diabetic rat kidney in vivo using the hemagglutinating virus of Japan (HVJ)-liposome method virtually abolished TGF-beta1 and plasminogen activator inhibitor-1 expression. Our results collectively indicate that AP-1 activation is crucial for mesangial cell proliferation and ECM production in response to high glucose and angiotensin II. Moreover, use of stable AP-1 decoy ODN combined with the highly effective HVJ-liposome method provides a novel potential molecular therapeutic strategy for the prevention of diabetic nephropathy.

Angiotensin II↗
PubMed2001

Antioxidative and antitumor promoting effects of [6]-paradol and its homologs.

Recently, considerable attention is focused on anti-carcinogenic phytochemicals, particularly those derived from medicinal or edible plants. [6]-Paradol, a pungent phenolic compound present in certain Zingiberaceae plants, is known to have antimicrobial and analgesic activities. The compound has been reported to attenuate promotion of skin carcinogenesis and TPA-induced ear edema in female ICR mice, and to induce apoptosis in cultured human promyelocytic leukemia (HL-60) cells. In this study, we performed several biochemical studies to evaluate and compare the cancer chemopreventive potential of [6]-paradol and its synthetic derivatives. [6]-Paradol and its synthetic nonpungent analog, [6]-dehydroparadol significantly decreased the incidence and the multiplicity of skin tumors initiated by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical application of [6]-paradol and its derivatives inhibited TPA-induced ear edema and H(2)O(2) production and myeloperoxidase activity in the dorsal skin of mice. Induction of TPA-induced mouse epidermal ornithine decarboxylase (ODC) activity and H(2)O(2)- and UV-induced formation of oxidized DNA bases in vitro were also attenuated by the above compounds. These results indicate that [6]-paradol and its derivatives possess the cancer chemopreventive potential.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation.

A wide array of phenolic substances, particularly those present in edible and medicinal plants, have been reported to possess substantial anticarcinogenic and antimutagenic activities. The majority of naturally occurring phenolics retain antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activity. Cyclooxygenase-2 (COX-2) inducible and nitric oxide synthase (iNOS) are important enzymes that mediate inflammatory processes. Improper up-regulation of COX-2 and/or iNOS has been associated with pathophysiology of certain types of human cancers as well as inflammatory disorders. Since inflammation is closely linked to tumor promotion, substances with potent anti-inflammatory activities are anticipated to exert chemopreventive effects on carcinogenesis, particularly in the promotion stage. Examples are curcumin, a yellow pigment of turmeric (Curcuma longa L., Zingiberaceae), the green tea polyphenol epigallocatechin gallate (EGCG), and resveratrol from grapes (Vitis vinifera, Vitaceae) that strongly suppress tumor promotion. Recent studies have demonstrated that eukaryotic transcription factor nuclear factor-kappa B (NF-kappa B) is involved in regulation of COX-2 and iNOS expression. Several chemopreventive phytochemicals have been shown to inhibit COX-2 and iNOS expression by blocking improper NF-kappa B activation. Multiple lines of compelling evidence indicate that extracellular-regulated protein kinase and p38 mitogen-activated protein kinase are key elements of the intracellular signaling cascades responsible for NF-kappa B activation in response to a wide array of external stimuli. Curcumin, EGCG and resveratrol have been shown to suppress activation of NF-kappa B. One of the plausible mechanisms underlying inhibition of NF-kappa B activation by aforementioned phytochemicals involves repression of degradation of the inhibitory unit I kappa B alpha, which hampers subsequent nuclear translocation of the functionally active subunit of NF-kappa B.

Animals↗
PubMed2001

Effect of protein kinase C inhibitor (PKCI) on radiation sensitivity and c-fos transcription.

PURPOSE: The human genetic disorder ataxia-telangiectasia (AT) is a multisystem disease characterized by extreme radiosensitivity. Although ionizing radiation was known to induce c-fos transcription and cellular protein kinase C (PKC) induces the expression of this immediate response gene, little is known about how mutated AT (ATM) or PKC-mediated signal transduction pathway modulates the c-fos gene transcription and gene expression. Here we have studied the effect of PKC inhibitor (PKCI) on radiation sensitivity and c-fos transcription in normal and AT cells, and also studied whether PKCI effect on c-fos occurs in Ras-dependent pathway. METHODS AND MATERIALS: Normal (LM217) and AT (AT5BIVA) cells were transfected with PKCI expression plasmid and integration and overexpression of PKCI was evaluated by polymerase chain reaction and northern blotting, respectively. Cells were irradiated at a dose of 5 Gy/min with 137Cs irradiator and harvested 48 h after irradiation and investigated apoptosis with TUNEL method. The c-fos transcription activity was studied by performing compute assisted tomography (CAT) assay of reporter gene after transfection of c-fos CAT plasmid into LM and AT cells. Overexpression of Ras protein in transfected cells was shown by western blotting. RESULTS: Our results demonstrated for the first time a role of PKCI on the radiation sensitivity and c-fos transcription in LM and AT cells. PKCI increased radiation induced apoptosis in LM cells (5% to 20%) but reduced apoptosis slightly in AT cells. The basal c-fos transcription activity is 70 times lower in AT cells than in LM cells. This c-fos transcription activity was repressed by overexpression of PKCI in LM cells but not in AT cells. After induction of c-fos by Ras protein, overexpression of PKCI repressed c-fos transcription in LM cells but not in AT cells. CONCLUSIONS: Overexpression of PKCI increased radiation sensitivity and repressed c-fos transcription in LM cells but not in AT cells, and this is related with Ras. These results suggest that the effect of PKCI on c-fos transcription activity is related with Ras dependent signal transduction pathways and these mechanisms are different between normal fibroblasts, LM and ATM mutated, AT cells. The data obtained by this study provided evidence for novel transcriptional difference between LM and AT cells and this may be a reason for increased radiation sensitivity of AT cells.

Apoptosis↗
PubMed2001

Cystic rectal duplication: a rare cause of neonatal bladder-outlet obstruction and hydronephrosis.

A case of cystic rectal duplication (RD) is presented. A 7-day-old female was admitted with acute urinary retention, voiding difficulty, and abdominal distention since she was 4 days of age. Ultrasound and abdominal computed tomography (CT) demonstrated a huge, cystic mass in the pelvis and abdomen that resulted in acute urinary retention and bilateral hydronephrosis. CT-guided drainage of the lesion followed by transabdominal surgical excision resulted in a cure. Pathologic examination demonstrated a RD lined by respiratory epithelium.

Cysts↗
PubMed2001

Correlation between 99mTc-pertechnetate uptakes and expressions of human sodium iodide symporter gene in breast tumor tissues.

We investigated a correlation between the expression of human sodium iodide symporter (hNIS) mRNA and the uptake of 99mTc-pertechnetate in 25 breast tumors. 99mTc-pertechnetate scintigraphy revealed positive uptake in 4 patients. The normalized mRNA expression of hNIS was higher in tumors with positive uptake on the scintigraphy (n=4, median 0.97, range 0.78-1.27) than that in negative uptake tumors (n=21, median 0.46, range 0.10-1.03, p < 0.005). 99mTc-pertechnetate uptake is correlated with the hNIS expression in the breast tumor.

Breast Neoplasms↗
PubMed2001

The role of inducible-nitric oxide in cocaine-induced kindling.

Experimentally naive male Sprague Dawley rats (weighing 85-110 g) were used to examine the role of inducible nitric oxide synthase (iNOS) in cocaine-induced kindling. Repeated administration of cocaine (45 mg/kg, i.p.) to Sprague Dawley male rats for 7 consecutive days produced a progressive increase in the convulsive responsiveness and death. Pretreatment with iNOS inhibitors, L-N6-(1-iminoethyl)lysine (NIL; 10 mg/kg, i.p.) and (-)-epigalloocatechin gallate (EGCG; 10 mg/kg, i.p.) 30 min before cocaine (45 mg/kg, i.p.) administration for 7 days attenuated the development of cocaine kindling and blocked cocaine-induced death. Results of NMDA receptor binding assay in the hippocampus showed a significant increase in the affinity without changes in the density in animals treated with cocaine, but there were no changes in these parameters in the cortex. Pretreatment with NIL or EGCG prior to cocaine administration abolished the cocaine-induced effect in the NMDA receptor affinity in the hippocampus. These results suggest that iNOS induction followed by an increase of NMDA receptor affinity in the hippocampus after repeated exposure to cocaine may participate in the process of the development of cocaine kindling.

Animals↗
PubMed2001

Schizophrenic delusions in Seoul, Shanghai and Taipei: a transcultural study.

In this transcultural study of schizophrenic delusions among patients in Seoul, Shanghai and Taipei, we discovered that both the frequency and content of delusions differed among the three groups; and that these differences could perhaps be explained by varying sociocultural and political situations. Delusional themes that are sensitive to sociocultural or political situations include guilt, love/sex, religion, somatic damage, economy/business and politics. Delusions regarding longevity, love/sex, dysmorphophobia/dysosmophobia, religion or supernatural matters, and espionage/spy stories were most frequent in Seoul patients. Those in Taipei predominantly had delusions about possession, religion or supernatural matters, hypnotism, and mass media/computers. Shanghai patients often had delusions of poisons, being prickled by poisoned needles, their brain and viscera extracted and being a family member of political authorities.

Adult↗
PubMed2001

A case of glomerulonephritis in association with pyogenic liver abscess.

Glomerulonephritis associated with visceral abscess is being increasingly recognized. The association of glomerulonephritis with visceral suppuration in the absence of endocarditis was first described by Whitworth and associates. Abscesses were most frequently located in the respiratory tract but have been reported at numerous other sites, including appendix, uterus, aorto-femoral bypass graft and cutaneous wound. This report documents the apparently rare occurrence of glomerulonephritis with acute renal failure in association with pyogenic liver abscess. The need for awareness of glomerulonephritis as a cause of acute renal failure in pyogenic liver abscess is highlighted.

Aged↗
PubMed2000

Protective effects of hemin and tetrakis(4-benzoic acid)porphyrin on bacterial mutagenesis and mouse skin carcinogenesis induced by 7, 12-dimethylbenz[a]anthracene.

Porphyrins which are widespread in nature can interfere with the actions of certain carcinogens and mutagens, and have also been used clinically in photodynamic therapy (PDT) of tumors. Porphyrins such as chlorophyll, chlorophyllin (CHL) and hemin are known to inactivate various mutagens by forming complexes with them. Tetrakis(4-benzoic acid)porphyrin (TBAP) has been developed as a photosensitizer for PDT and its metal complex, MnTBAP has been shown to be efficacious in a variety of in vitro and in vivo oxidative stress models of human diseases. In the present study, we have found that TBAP and hemin exert concentration-related inhibition of his(+) reversion in Salmonella typhimurium TA100 induced by 7, 12-dimethylbenz[a]anthracene (DMBA), and significantly reduced both incidence and multiplicity of skin tumors when topically applied prior to treatment of 12-O-tetradecanoylphorbol-13-acetate in female ICR mice. Covalent DNA binding of DMBA in mouse skin was also significantly inhibited by topical application of TBAP or hemin as well as CHL. These results suggest the chemopreventive potential of compounds containing a porphyrin nucleus.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Chlorophyllin suppression of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells.

Chlorophyllin (CHL), a water-soluble derivative of chlorophyll, functions as an anticarcinogen and antioxidant. In the present study, we investigated the effect of CHL on nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Treatment with CHL inhibited nitric oxide production in the LPS-stimulated RAW 264. 7 cells in a dose-related manner. Competitive RT-PCR analysis, using a DNA competitor as an internal standard, demonstrated that the treatment with 1, 10, and 50 microM CHL decreased LPS-induced iNOS mRNA expression in a concentration-dependent manner. Since the expression of the iNOS gene is mainly regulated by NF-kappaB, we then examined the effects of CHL on the NF-kappaB DNA binding activity, using an electrophoretic mobility shift assay. CHL down-regulated the NF-kappaB DNA binding on its cognate recognition site at the concentrations just noted. Employing a transfection and reporter gene expression system with p(NF-kappaB)(3)-chloramphenicol acetyl transferase (CAT), the treatment of CHL produced a dose-dependent inhibition of CAT activity in RAW 264.7 cells. Furthermore, CHL partially restored LPS-decreased IkappaBalpha, an inhibitory protein against NF-kappaB activation, in the cytosolic extract from the LPS-treated cells determined by immunoblot analysis. CHL also protected the hydroxyl radical-induced cytotoxicity in RAW 264.7 cells, indicating its antioxidant effect. These results suggest that CHL suppresses the nitric oxide production and iNOS mRNA expression mediated by the inhibition of NF-kappaB activation, and its action mechanism may be based on its antioxidant effect.

Animals↗
PubMed2000

Retargeting T cell-mediated inflammation: a new perspective on autoantibody action.

To understand the pathogenesis of organ-specific autoimmune disease requires an appreciation of how the T cell-mediated inflammation is targeted, and how the organ function is compromised. In this study, autoantibody was documented to influence both of these parameters by modulating the distribution of T cell-mediated inflammation. The murine autoimmune ovarian disease is induced by immunization with the ZP3330-342 peptide of the ovarian zona pellucida 3 glycoprotein, ZP3. Passively transferred or actively induced Ab to ZP3335-342 bound to the zona pellucida in the functional and degenerative ovarian follicles, and the ovaries remained histologically normal. Transfer of ZP3330-342 peptide-specific T cells targeted the degenerative follicles and spared the functional follicles, and the resultant interstitial oophoritis was associated with unimpaired ovarian function. Unexpectedly, the coexistence of ZP3330-342 peptide-specific T cells and zona-bound autoantibody led to a dramatic translocation of the ovarian inflammation to the growing and mature ovarian follicles, with destruction of the ovarian functional unit. Ab retargeted both Th1-induced mononuclear inflammation and Th2-induced eosinophilic inflammation, and retargeting was induced by murine and rat polyclonal Abs to multiple distinct native B cell determinants of the zona pellucida. Therefore, by reacting with the native determinants in tissue Ag, Ab alters the distribution of T cell-mediated inflammation, and results in destruction of the functional units of the target organ. We propose that this is a clinically important and previously unappreciated element of Ab action in autoimmune disease.

Amino Acid Sequence↗