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Biomedical subjects

H K Oh

Publications and source records attributed to H K Oh.

At least 19 recordsLinked to original sources
PubMed2006

Systemic herpes simplex virus infection following cadaveric renal transplantation: a case report.

Herpes simplex virus (HSV) infection usually occurs in immunocompromised or severely debilitated patients. It is not so common in patients with renal transplants. The diagnosis can only be made histologically. It usually occurs during or shortly after treatment of graft rejection with high-dose steroids. We have recently experienced a case of HSV esophagitis and nephropathy in the renal allograft biopsy, which was identified by histology, immunostaining, and electron microscopy. A 43-year-old woman underwent cadaveric renal transplantation with cyclosporine and prednisolone treatment. Twelve months later, she developed renal insufficiency and proteinuria. Allograft renal biopsy showed some evidence of acute rejection. She was treated with 3 successive days of methylprednisolone (1.0 g/d) intravenously and continued tapering of steroids. Three weeks after steroid pulse therapy, she had throat pain, oral cavity ulcer, dysphagia, and febrile sensation. Esophagoscopy revealed multiple confluent ulcers in the whole esophagus, and biopsy showed enlarged epithelial cells with prominent nuclei. Immunohistochemically, the epithelial cells were positive with a monoclonal antibody to HSV type 1. She was started on acyclovir intravenously, which was continued for a week. After a week, her symptoms began to improve and repeat endoscopy showed no residual esophagitis. A renal allograft infection with HSV can persist in heavily immunosuppressed patients with recurrent rejection episodes. HSV mainly affects tubular cells causing necrosis, a major reason for functional deterioration. A biopsy is required for diagnosis.

Acyclovir↗
PubMed2004

KNT-artificial neural network model for flux prediction of ultrafiltration membrane producing drinking water.

This paper describes the prediction of flux behavior in an ultrafiltration (UF) membrane system using a Kalman neuro training (KNT) network model. The experimental data was obtained from operating a pilot plant of hollow fiber UF membrane with groundwater for 7 months. The network was trained using operating conditions such as inlet pressure, filtration duration, and feed water quality parameters including turbidity, temperature and UV254. Pre-processing of raw data allowed the normalized input data to be used in sigmoid activation functions. A neural network architecture was structured by modifying the number of hidden layers, neurons and learning iterations. The structure of KNT-neural network with 3 layers and 5 neurons allowed a good prediction of permeate flux by 0.997 of correlation coefficient during the learning phase. Also the validity of the designed model was evaluated with other experimental data not used during the training phase and nonlinear flux behavior was accurately estimated with 0.999 of correlation coefficient and a lower error of prediction in the testing phase. This good flux prediction can provide preliminary criteria in membrane design and set up the proper cleaning cycle in membrane operation. The KNT-artificial neural network is also expected to predict the variation of transmembrane pressure during filtration cycles and can be applied to automation and control of full scale treatment plants.

Automation↗
PubMed2001

Management of advanced mandibular osteoradionecrosis with free flap reconstruction.

BACKGROUND: The purpose of this study was to assess the effectiveness of free tissue transfer for treatment of advanced mandibular osteoradionecrosis (ORN) in head and neck cancer patients. METHODS: We reviewed 29 patients who were treated for advanced mandibular ORN by radical resection and reconstruction with free flaps at our institution. All patients had either failed to respond to conservative treatment, including hyperbaric oxygen therapy and debridement or had pathological fracture due to ORN. RESULTS: Twenty-four vascularized bone (17 fibula, five iliac, and two scapula), four rectus abdominis myocutaneous, and one radial forearm fasciocutaneous free flaps were used. The complications occurred in 6 of 29 patients (21%). A total of four flaps (14%) were lost. The mean follow-up was 2 years 9 months. All patients had complete resolution of ORN symptoms. No evidence of ORN recurrence was observed in any patient. CONCLUSION: For advanced osteoradionecrosis of the mandible, radical resection followed by reconstruction using free flap provides a reliable means of obtaining good wound healing with acceptable aesthetic and functional results.

Adult↗
PubMed2001

The modified human DNA repair enzyme O(6)-methylguanine-DNA methyltransferase is a negative regulator of estrogen receptor-mediated transcription upon alkylation DNA damage.

Cell proliferation requires precise control to prevent mutations from replication of (unrepaired) damaged DNA in cells exposed spontaneously to mutagens. Here we show that the modified human DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (R-MGMT), formed from the suicidal repair of the mutagenic O(6)-alkylguanine (6RG) lesions by MGMT in the cells exposed to alkylating carcinogens, functions in such control by preventing the estrogen receptor (ER) from transcription activation that mediates cell proliferation. This function is in contrast to the phosphotriester repair domain of bacterial ADA protein, which acts merely as a transcription activator for its own synthesis upon repair of phosphotriester lesions. First, MGMT, which is constitutively present at active transcription sites, coprecipitates with the transcription integrator CREB-binding protein CBP/p300 but not R-MGMT. Second, R-MGMT, which adopts an altered conformation, utilizes its exposed VLWKLLKVV peptide domain (codons 98 to 106) to bind ER. This binding blocks ER from association with the LXXLL motif of its coactivator, steroid receptor coactivator-1, and thus represses ER effectively from carrying out transcription that regulates cell growth. Thus, through a change in conformation upon repair of the 6RG lesion, MGMT switches from a DNA repair factor to a transcription regulator (R-MGMT), enabling the cell to sense as well as respond to mutagens. These results have implications in chemotherapy and provide insights into the mechanisms for linking transcription suppression with transcription-coupled DNA repair.

Alkylation↗
PubMed1998

Fibrillary glomerulonephritis in a renal allograft.

Fibrillary glomerulonephritis is an uncommon disease seen in approximately 1% of all native kidney biopsy specimens. We present here a case of a 40-year-old white woman with the rapid loss of graft function secondary to fibrillary glomerulonephritis within 7 days of receiving a living-related renal allograft. This case emphasizes the values of combining urinalysis with prompt allograft kidney biopsy in recipients with an elevated serum creatinine posttransplantation. When one encounters rapidly progressing glomerulonephritis or a pulmonary-renal syndrome in the immediate posttransplantation period, fibrillary glomerulonephritis must be considered in the differential diagnosis. Because of a high recurrence rate and no available treatment to modify a potentially malignant course of this disease, we recommend caution when considering these patients for transplantation.

Actin Cytoskeleton↗
PubMed1998

Implication of localization of human DNA repair enzyme O6-methylguanine-DNA methyltransferase at active transcription sites in transcription-repair coupling of the mutagenic O6-methylguanine lesion.

DNA lesions that halt RNA polymerase during transcription are preferentially repaired by the nucleotide excision repair pathway. This transcription-coupled repair is initiated by the arrested RNA polymerase at the DNA lesion. However, the mutagenic O6-methylguanine (6MG) lesion which is bypassed by RNA polymerase is also preferentially repaired at the transcriptionally active DNA. We report here a plausible explanation for this observation: the human 6MG repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is present as speckles concentrated at active transcription sites (as revealed by polyclonal antibodies specific for its N and C termini). Upon treatment of cells with low dosages of N-methylnitrosourea, which produces 6MG lesions in the DNA, these speckles rapidly disappear, accompanied by the formation of active-site methylated MGMT (the repair product of 6MG by MGMT). The ability of MGMT to target itself to active transcription sites, thus providing an effective means of repairing 6MG lesions, possibly at transcriptionally active DNA, indicates its crucial role in human cancer and chemotherapy by alkylating agents.

Alkylating Agents↗
PubMed1998

Two low-dose OKT3 induction regimens following renal transplantation--clinical experience at a single center.

Experience with quadruple-drug induction therapy with two regimens of low-dose OKT3 in renal transplant patients was evaluated. Group I received 5.0 mg OKT3 in the operating room and on day 1, followed by 2.5 mg/d for a total dose and duration of 40 mg and 14 d, respectively, and group II received 14 d of OKT3 2.5 mg/d (a total dose of 35 mg). Rejection episodes developed in 21% of patients: 29% of group I vs. 17% of group II. In groups I and II, the mean number of days until first rejection was 134 and 119 d, respectively, and delayed graft function was observed in 24 vs. 13% of patients, respectively. Cytokine release syndrome was noted in 95% of group I patients and in 78% of group II patients. The overall incidence of infections did not differ significantly between the two groups; however, the incidence of oral candidiasis was higher in group II (30 vs. 11% in group I, p = 0.021) and the incidence of herpes simplex virus infection was higher in group I (13 vs. 1% in group II, p = 0.015). The average length of hospital stay was 6.7 d in group I and 6.2 d in group II. The current pharmacy charge for a 2.5-mg vial of OKT3 is 28% lower for a 5.0-mg vial. Our study suggests that by using either low-dose OKT3 regimen renal transplant patients can be safely treated with shortened hospital stays, lower pharmacy costs, and without increased incidence of graft loss or patient morbidity.

Adult↗
PubMed1998

Insulin allergy resolution following pancreas transplantation alone.

Clinically significant immunological reactions to exogenous insulin are classified as local or generalized. Most of the insulin allergies are local reactions which usually improve or resolve spontaneously. Generalized allergic reactions to insulin range in severity from simple urticaria to life-threatening anaphylaxis. Most of the allergic reactions to exogenous insulin are antibody-mediated reactions to antigens such as zinc, protamine, non-insulin proteins, and aggregates of insulin molecules as well as animal antigens. Immunologic reactions to endogenous insulin usually result in insulin resistance. Herein, we report a case in which systemic insulin allergy was intractable, thus requiring a pancreas transplantation which is the first of its case according to the International Pancreas Transplant Registry/United Network for Organ Sharing (IPTR/UNOS) Registry.

Adult↗
PubMed1996

Conformational change in human DNA repair enzyme O6-methylguanine-DNA methyltransferase upon alkylation of its active site by SN1 (indirect-acting) and SN2 (direct-acting) alkylating agents: breaking a "salt-link".

Human O6-methylguanine-DNA methyltransferase (MGMT) repairs DNA by transferring alkyl (R-) adducts from O6-alkylguanine (6RG) in DNA to its own cysteine residue at codon 145 (formation of R-MGMT). We show here that R-MGMT in cell extracts, which is sensitive to protease V8 cleavage at the glutamic acid residues at codons 30 (E30) and 172 (E172), can be specifically immunoprecipitated with an MGMT monoclonal antibody, Mab.3C7. This Mab recognizes an epitope of human MGMT including the lysine 107 (K107) which is within the most basic region that is highly conserved among mammalian MGMTs. Surprisingly, the K107L mutant protein is repair-deficient and readily cleaved by protease V8 similar to R-MGMT. We propose that R-MGMT adopted an altered conformation which exposed the Mab.3C7 epitope and rendered that protein sensitive to protease V8 attack. This proposal could be explained by the disruption of a structural "salt-link" within the molecule based on the available structural and biochemical data. The specific binding of Mab.3C7 to R-MGMT has been compared with the protease V8 method in the detection of R-MGMT in extracts of cells treated with low dosages of methyliodide (SN2) and O6-benzylguanine. Their identical behaviors in producing protease V8 sensitive R-MGMT and Mab.3C7 immunoprecipitates suggest that probably methyl iodide (an ineffective agent in producing 6RG in DNA) can directly alkylate the active site of cellular MGMT similar to O6-benzylguanine. The effectiveness of MeI in producing R-MGMT, i.e., inactivation of cellular MGMT, indicates that this agent can increase the effectiveness of environmental and endogenously produced alkylating carcinogens in producing the mutagenic O6-alkylguanine residues in DNA in vivo.

Alkylating Agents↗
PubMed1995

Inhibition of PDGF-induced phospholipase D but not phospholipase C activation by herbimycin A.

It is known that PDGF-induced phospholipase D (PLD) activation occurs downstream of phospholipase C gamma 1 (PLC-gamma 1) activation. Herbimycin A, a specific inhibitor of Src family tyrosine kinase, dose-dependently inhibited PDGF-induced PLD activation (IC50 of 8 micrograms/ml) without affecting PLC-gamma 1 activation and significantly reduced PDGF-induced tyrosine phosphorylations of 40-46 kD and 60 kD proteins in PLC-gamma 1-overexpressing NIH 3T3 gamma 1 cells. These results suggest that PLC activation is necessary but not sufficient for PDGF-induced PLD activation. Tyrosine phosphorylation of p40-p46 and p60 is thought to be involved in PDGF-induced activation of PLD but not of PLC.

3T3 Cells↗
PubMed1994

A method for simultaneous identification of human active and active-site alkylated O6-methylguanine-DNA methyltransferase and its possible application for monitoring human exposure to alkylating carcinogens.

Cells resist the major mutagenic effects of alkylating agents by the action of O6-methylguanine-DNA methyltransferase (MGMT), which transfers the alkyl (R) group of O6-alkylguanine, produced in DNA by these chemicals, to a cysteine residue in its active site (formation of R-MGMT). We demonstrate that cellular R-MGMT (which represents a record or memory within the cells exposed to these chemicals) can be assayed by its sensitivity toward proteolysis by protease V8. The possible use of this assay for monitoring exposure to alkylating carcinogens was investigated by using cultured cells and a preliminary study with the use of human blood from normal subjects and patients undergoing chemotherapy. Cultured cell experiments show that R-MGMT is sufficiently stable for the monitoring purpose and its level bears a dose-response relationship to the concentrations of the alkylating agent used. Interestingly, experiments with blood from patients undergoing chemotherapy show a gradual formation of R-MGMT in 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and an induced MGMT deficiency in cyclophosphamide-treated patients. The use of this methodology, which allows for the possible quantification of active MGMT (cellular DNA repair capacity) and R-MGMT (recent exposure) simultaneously, in monitoring human exposure to alkylating carcinogens is discussed.

Adolescent↗
PubMed1994

Plasma type IV collagen and fibronectin concentrations in diabetic patients with microangiopathy.

In diabetes mellitus, thickening of basement membrane in capillaries and small vessels is a well-known finding and important in the progression of diabetic microangiopathy. We evaluated whether the plasma levels of type IV collagen and fibronectin, which are important factors of basement membrane, are related with the presence of diabetic microangiopathy. Plasma type IV collagen and fibronectin levels were measured in 40 healthy controls (Mean +/- SD, age; 50.3 +/- 5.5 yr) and 94 diabetic patients (age; 52.4 +/- 13.5 yr) with and without microvascular complications. The mean plasma levels of type IV collagen (5.3 +/- 2.9 ng/ml) and fibronectin (474.4 +/- 119.4 ug/ml) in diabetic patients were significantly higher (p < 0.01) than in healthy controls (3.7 +/- 1.3 ng/ml and 319 +/- 50.9 ug/ml). The mean plasma level of type IV collagen in diabetic patients with complications (6.6 +/- 3.7 ng/ml) was significantly higher (p < 0.01) than in those without complications (4.3 +/- 1.7 ng/ml) and became higher in more complicated patients. Furthermore, the severity of retinopathy and several indicators of nephropathy such as serum BUN, creatinine and proteinuria were closely associated with plasma type IV collagen level and a significant correlation was found between plasma type IV collagen and creatinine clearance (r = -0.31, p < 0.001). There was no significant difference in plasma fibronectin concentrations, however, between the diabetic patients with complications and those without complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Removal of lymphocytotoxic antibodies by pretransplant immunoadsorption therapy in highly sensitized renal transplant recipients.

A high level of panel-reactive antibodies (PRA) in potential renal transplant recipients is associated with a long waiting time until transplantation and correlates inversely with graft outcome. We report our experience with the employment of immunoadsorption (IA) using a column composed to sepharose-bound staphylococcal protein A (which has a relatively selective affinity for binding IgG compared with other immunoglobulins) to decrease the PRA levels and expedite transplantation in 6 highly sensitized potential renal transplant recipients (1 primary and 5 awaiting second transplants). All patients had PRA levels of greater than or equal to 70% for a duration of 1 year prior to IA. Only patients with antibody specificity localized to 1 or 2 HLA A or B antigens were accepted for the study. IA procedures were performed on alternate days until a twofold decrease in antibody titer had occurred (maximum: 6 procedures). Repeat procedures were initiated if the HLA antibody titer returned to its baseline value. Intravenous cyclophosphamide (CY) (10 mg/kg/day every 3 weeks) and methylprednisolone (MP) (0.5 mg/kg/day) were provided as adjunctive immunosuppression until transplantation. A total of 44 immunoadsorption procedures were performed (27 primary and 17 repeat) with treatment of 2.49 +/- 0.02 plasma volumes per session. Serum IgG concentration decreased 95 +/- 3% and PRA activity decreased 75 +/- 16% after the primary treatment course. Four patients received cadaveric grafts within 3.7 +/- 1.2 months following the last IA procedure. Three grafts are functioning at 1 year, 8 months, and 8 weeks posttransplant. The remaining graft demonstrated primary nonfunction. All four patients had a past positive crossmatch using pre-IA sera with their respective donors. Patients not transplanted exhibited rapid resynthesis of IgG and a return of the PRA towards baseline levels within a few weeks after IA. We conclude that IA can effectively remove HLA antibodies and expedite graft availability in highly sensitized patients.

Adult↗
PubMed1991

Epidural morphine on ventilatory function in chest trauma and thoracotomy patients.

Epidural morphine injection was done in nineteen patients who had been admitted from March to August 1990 to the Intensive Care Unit, Severance Hospital, Yonsei Medical Center for respiratory care including ventilator care. Morphine suplphate, 2.67 +/- 0.27 mg was injected one to three times to four patients after chest trauma, and to fifteen patients after thoracotomy. Tidal volume and vital capacity were increased from 4.45 +/- 0.48 and 8.31 +/- 0.50 to 6.91 +/- 0.41 and 12.81 +/- 0.73 mg/kg. However, respiratory rates decreased from 26.07 +/- 1.41 to 20.07 +/- 1.16/min. Inspiratory force increased from -13.40 +/- 1.31 to -26.53 +/- 1.82 cmH2O. Pain score decreased from 9.22 +/- 0.57 to 3.56 +/- 0.83 during this period. PaCO2 did not differ significantly (39.33 +/- 1.13 and 39.48 +/- 1.42 mmHg). Side effects such as pruritus and urinary retention were treated with naloxone 7 approximately 10 ng/kg/min. Mean arterial pressure and pulse rates stayed stable during the study periods. Ventilator hours and ICU stays differed from the control group. However, the duration was not statistically significant. The control group consisted of patients who were admitted during the six months from September 1989 to February 1990 to the ICU for respiratory care, without epidural morphine injection.

Adult↗
PubMed1990

A prospective controlled trial of cold-storage versus machine-perfusion preservation in cadaveric renal transplantation.

A prospective controlled study was carried out in 60 consecutive cadaver renal donors comparing cold storage to pulsatile machine-perfusion preservation. Each donor served as its own control, by allocating one of the kidneys to each of the two preservation methods. There were 51 evaluable pairs of kidneys. Recipient age, panel-reactive antibody level, history of prior renal transplant, and immunosuppressive regimen were similar in the two preservation groups. Almost all recipients were treated with cyclosporine, and over 50% received antilymphoblast globulin. Total cold ischemic time was 1262 +/- 387 min in the machine-perfused group and 1309 +/- 426 min in the cold-storage group (P = NS). Prolonged ischemia (greater than 24 hr) occurred in 31% of machine-perfused and 22% of cold-stored kidneys (P = NS). Post-operative serum creatinine levels at 1, 7, and 30 days posttransplant were similar in both groups. Dialysis requirements were also similar, with 21 recipients of machine-perfused kidneys (41%) requiring at least one dialysis treatment compared to 16 patients (31%) in the cold-stored group (P = NS); the mean number of dialysis treatments required was 3.14 +/- 1.46 and 3.06 +/- 1.29, respectively (P = NS). Long ischemic time (greater than 24 hr) was associated with a higher rate of dialysis requirement in both groups, but in neither case did this achieve statistical significance. The distribution of graft losses within the first 30 days was similar in both groups, and the incidence of preservation-related graft failure was not significantly different. These results demonstrate that, in the cyclosporine era, machine perfusion offers no significant advantages over cold storage for cadaver renal preservation. Because machine perfusion is considerably more expensive and cold storage is simpler and facilitates the logistics of organ sharing, we recommend simple hypothermic storage of renal allografts as the preservation method of choice.

Analysis of Variance↗
PubMed1990

Clinical experiences of fiberoptic bronchoscopy in patients with respiratory failure in the intensive care unit.

Seventy-nine fiberoptic bronchoscopies were performed in 46 Patients during 2 years in the Intensive Care Unit of Severance Hospital, Yonsei Medical Center. Bronchoscopies were done more than twice in 13 patients. Forty-three bronchoscopies were done through the orotracheal tube in 27 patients, and narcotics and sedatives such as morphine sulfate, diazepam and lorazepam were added with pancuronium bromide during 52 bronchoscopy procedures in 21 patients. Ventilatory support was accomplished by control mode ventilation for 63 bronchoscopies in 37 patients. Twenty-four patients were from the surgical department, and 37 bronchoscopies were performed in 18 patients in a post-thoracotomy state. Twenty-two patients were nonsurgical patients. We performed 48 bronchoscopies in 26 patients to treat lung haziness, 14 bronchoscopies in 3 patients to confirm the operative anastomosis after pneumonectomy or tracheoplasty, and 11 bronchoscopies to confirm the airway patency and vocal cord movement. We obtained good results from 41 bronchoscopies performed for therapeutic purposes and 28 bronchoscopies done for diagnostic purposes. But in 4 patients with pleural effusion and pneumonia, we could not get any improvement in chest X-ray taken after bronchoscopy. We suggested other procedures in 6 patients for diagnosis or treatment, such as suspension laryngoscopy, thoracentesis, ultrasonogram and laser surgery.

Airway Obstruction↗