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Biomedical subjects

J J Park

Publications and source records attributed to J J Park.

At least 19 recordsLinked to original sources

NOS3 gene polymorphisms and exercise hemodynamics in postmenopausal women.

We tested whether the G894T and T-786C NOS3 polymorphisms were associated with exercise cardiovascular (CV) hemodynamics in sedentary, physically active, and endurance-trained postmenopausal women. CV hemodynamic parameters including heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures and cardiac output (Q), as determined by acetylene rebreathing, stroke volume (SV), arteriovenous oxygen difference (a-vO2 diff), and total peripheral resistance (TPR) were measured during submaximal (40, 60, 80 %) and maximal (approximately 100 % VO2max) exercise. NOS3 G894T genotype was not significantly associated, either independently or interactively with habitual physical activity (PA) level, with SBP, Q, TPR, or a-vO2 diff during submaximal or maximal exercise. However, NOS3 894T non-carriers had a higher submaximal exercise HR than NOS3 894T allele carriers (120 +/- 2 vs. 112 +/- 2 beats/min, p = 0.007). NOS3 894T allele carriers had a higher SV than 894T non-carriers (78 +/- 2 vs. 72 +/- 2 ml/beat, p = 0.03) during submaximal exercise. NOS3 894T non-carriers also had a higher maximal exercise HR averaged across habitual PA groups than T allele carrier women (165 +/- 2 vs. 158 +/- 2 beats/min, p = 0.04). NOS3 894T allele carriers also tended to have a higher SV during maximal exercise than 894T non-carriers (70 +/- 2 vs. 64 +/- 2 ml/beat, p = 0.08). NOS3 T-786C genotype was not significantly associated, either independently or interactively, with any of the CV hemodynamic measures during submaximal or maximal exercise. These results suggest an association of NOS3 G894T genotype with submaximal and maximal exercise CV hemodynamic responses, especially HR, in postmenopausal women.

Blood Pressure↗

Association of nodular regenerative hyperplasia of the liver with porto-pulmonary hypertension in a patient with systemic lupus erythematosus.

A 37-year old woman with systemic lupus erythematosus (SLE) complicated by pulmonary hypertension (PHT) was admitted to evaluate abnormal liver function. Radiological imaging study, including ultrasonography, computed tomography and magnetic resonance imaging and upper gastrointestinal endoscopy, revealed multiple hepatic nodules, hepatosplenomegaly and esophageal varices. Percutaneous needle liver biopsy showed non-cirrhotic hepatic nodules with hyperplastic hepatocytes surrounded by atrophic hepatocytes, confirming the diagnosis of nodular regenerative hyperplasia (NRH) associated with non-cirrhotic portal hypertension (PT). NRH of the liver is known to be a very rare hepatic manifestation in rheumatic diseases. This case shows the association of NRH with porto-pulmonary hypertension in SLE.

Adult↗

Retinoic acid-mediated induction of neurons and glial cells from human umbilical cord-derived hematopoietic stem cells.

Recent studies reporting trans-differentiation of mononucleated cells derived from human umbilical cord blood into neuronal cells aroused interest among investigators for their clinical implication and significance in regenerative medicine. In the present study, purified populations of hematopoietic stem cells were isolated via magnetic bead sorting and fluorescence-activated cell sorter (FACS) using a specific CD133 antibody, a cell type-specific marker for hematopoietic stem cells, and grown in culture in the presence of retinoic acid (RA). CD133+ hematopoietic stem cells expressed neuronal and glial phenotypes after RA treatment. RT-PCR analysis indicated that the RA treated CD133+ cells expressed mRNA transcripts for ATP-binding cassettes transporter ABCG2 (a universal stem cell marker), nestin (a specific cell type marker for neural stem cells), Musashi1 (a specific marker for neural stem cells) and RA receptors (RAR) including RAR-alpha, RAR-beta, and retinoid X receptor (RXR)-gamma. RA-treated CD133+ cells expressed mRNA transcripts for neuron-specific markers neurofilament proteins (NF-L, -M, -H) and synaptophysin as determined by RT-PCR, structural proteins characteristic of neurons including tubulin beta III and neuron specific enolase (NSE) by Western blot, and neuron-specific markers NeuN and microtubule-associated protein-2 (MAP2) by immunocytochemistry. RA-treated CD133+ cells also expressed the astrocyte-specific marker glial fibrillary acidic protein (GFAP), as demonstrated by RT-PCR, Western blot, and immunocytochemistry. In addition, RA-treated CD133+ cells expressed cell type-specific markers for oligodendrocytes including myelin basic protein (MBP) as shown by RT-PCR, proteolipid protein (PLP) by Western blot analysis, and cyclic nucleotide phosphodiesterase (CNPase) by immunostaining. Upregulated expression of several basic helix-loop-helix (bHLH) transcription factors important for early neurogenesis, including Otx2, Pax6, Wnt1, Olig2, Hash1 and NeuroD1, was also demonstrated in CD133+ cells after RA treatment. These results indicate that human cord blood-derived CD133+ hematopoietic stem cells could trans-differentiate into neural cell types of neuron-like cells, astrocytes, and oligodendrocytes by RA treatment.

Cells, Cultured↗

Assessing quality of life in Australian patients with Graves' ophthalmopathy.

AIMS: To determine quality of life and adequacy of education and counselling in Australian patients with Graves' ophthalmopathy during the course of their illness. METHODS: A cross sectional study was conducted at the orbital and endocrinology clinics of Royal Brisbane Hospital on 162 consecutive patients with Graves' ophthalmopathy who were managed between the 1992 and 2000. The Graves' ophthalmopathy quality of life (GO-QOL) survey modified for Australian conditions was distributed to study participants. Of the 19 questions asked, nine questions related to visual functioning, eight questions were about the psychosocial consequences of changed appearance, and two questions referred to education and counselling. Additionally, clinical data on the severity of illness were collected retrospectively from the medical notes of these patients. RESULTS: Completed questionnaires were received from 128 patients. The majority of patients reported limitations in daily activities such as hobbies, driving, watching television and reading, as well as impaired self confidence. The mean GO-QOL scores in this study were (100 representing maximum QOL): visual functioning 59.0 (SD 28.0), psychosocial consequences of changed appearance 54.5 (28.4), and education and counselling 59.1 (38.8). Only about a quarter of patients indicated that education and counselling were adequate and helpful. CONCLUSION: Graves' ophthalmopathy profoundly affects QOL and adequate education and counselling are essential for helping patients to cope with their illness. The GO-QOL survey is a simple, practical tool that can be used easily in a clinic to determine the QOL issues in subjects with Graves' ophthalmopathy.

Activities of Daily Living↗

Wave-front phase measurements of high-order harmonic beams by use of point-diffraction interferometry.

We report the wave-front phase measurement of high-order harmonics employing point-diffraction interferometry. The high-order harmonics generated in a gas-filled hollow tube showed excellent spatial coherence over nearly the whole cross section of the harmonic beams. Using this coherent harmonic source in the extreme-ultraviolet-soft-x-ray region, we have demonstrated the operation of a point-diffraction interferometer and measured the wave-front phase of high-order harmonics.

Journal Article↗

Emission of a hot electron jet from intense femtosecond-laser-cluster interactions.

A directional hot electron jet with energy higher than 100 keV was generated along the laser propagation direction from Ar clusters irradiated with a laser pulse of duration 28 fs and intensity 1 x 10(17) W/cm(2). The hot electron jet was detected only with linearly polarized laser pulses, not with circularly polarized pulses. Channel betatron resonance is believed to be the main accelerating mechanism for this directional hot electron jet.

Journal Article↗

Autologous cardiomyocyte transplantation in an ovine myocardial infarction model.

BACKGROUND: To evaluate the possibility of autologous cardiomyocyte transplantation, we transplanted cultured autologous cells into an infarct region developed by coronary artery ligation in an ovine model. MATERIALS AND METHODS: A chronic heart failure model with a considerable portion of myocardial infarction was created in sheep using sequential ligation of the homonymous artery and its diagonal branch. Autologous cardiomyocytes were cultured and isolated from the right ventricular infundibulum. After a predetermined interval (one animal for two months and the other for three months), the two animals were reanesthetized and a suspension of cultured autologous vetricular cells in 0.3 ml of culture medium (1.2 x 10(7) cells) was injected into the center of three out of the four sites in the infarcted area using a tuberculin syringe. The same amount of culture medium was injected with an identical procedure into the center of the remaining site, as control. The animals were kept alive for a further month, and then sacrificed for postmortem heart examinations. Light microscopic analysis and immunohistochemical study for myoglobin were done. RESULTS AND CONCLUSIONS: On postmortem gross examination, well-demarcated thin-walled anteroseptal infarcts with chamber enlargement were clearly seen in specimens from the two animals. Microscopic analysis showed homogenous fibrosis throughout the infarcted areas. In both animals, one of the three sites of cardiomycyte injection showed an islet of cardiomyocytes in the mid-myocardium, while none were observed in the control site of either animal. A layer of cardiomyocytes was observed in subendocardial regions, as it was in the control areas. In conclusion, cardiomyocyte transplantation into the infarct regions developed by coronary artery ligation in an ovine model was achieved with only limited success. An understanding of why only 33% of cardiomyocyte-injection sites demonstrated viable cardiomyocytes, in the form of tiny cell islets, remains to be elucidated.

Animals↗

Human thioredoxin reductase is efficiently inhibited by (2,2':6',2' '-terpyridine)platinum(II) complexes. Possible implications for a novel antitumor strategy.

Malignant neoplasms of the brain represent the second leading cause of cancer-related mortality in children under the age of 15. The prognosis of patients with glioblastoma multiforme, the most malignant type of gliomas, remains poor offering a median survival time of only 1 year. (2,2':6',2"-Terpyridine)platinum(II) complexes are known to possess DNA-intercalating activity and have been shown to be potential chemotherapeutic agents. In the present study we identified the selenoenzyme thioredoxin reductase (TrxR) as a major target of (2,2':6',2"-terpyridine)platinum(II) complexes. New complexes were synthesized in order to optimize this inhibition. The NADPH-reduced enzyme is inhibited almost stoichiometrically by the complexes involving a reversible competitive and an irreversible tight-binding component. For the most potent inhibitor, N,S-bis(2,2':6',2"-terpyridine)platinum(II)-thioacetimine trinitrate, the K(i) for the competitive component of the inhibition is 4 nM and the IC(50) for the tight-binding component is 2 nM after an incubation time of 5 min. The closely related but non-selenium-containing enzyme glutathione reductase is much less inhibited (by a factor of >1000). The platinum complexes were found to strongly inhibit the proliferation of three different glioblastoma cell lines as well as of two different head-and-neck squamous carcinoma cell lines. In a glioblastoma cell culture, less than 10 microM of a platinum(II) compound caused an initial drop of hTrxR activity which was followed by an increase of activity in the surviving cells. A 10 microM inhibitor added every 24 h led to 4% residual hTrxR activity but 100% glutathione reductase activity in the cells surviving for 67 h. The potential of (2,2':6',2"-terpyridine)platinum(II) complexes acting simultaneously at two different intracellular targets-hTrxR and DNA-as antitumor agents is discussed.

2,2'-Dipyridyl↗

Age-related change in the number of neurons in the human vestibular ganglion.

Dysequilibrium of aging in humans has been speculated to arise from progressive deterioration within anatomical components of the vestibular system. An integral part of this system is vestibular ganglions, which are bipolar neurons that relay peripheral vestibular information to the central nervous system. To assess the effect of aging on the number of human vestibular ganglion neurons, assumption-free stereology in the form of the optical fractionator was used on 20 serially sectioned archival human temporal bone specimens. Donors had no history of vestibular pathology and ranged in age from 2 to 88 years. An average of 25,812 (coefficient of variation = 0.13) vestibular ganglion neurons was found throughout this age range, a significant departure from the results of past studies. Logistics-based regression analysis pointed to a nonlinear pattern of decline in the neuronal population: the number of cells remained roughly constant at about 28,952 cells in youth and then declined gradually between 30 and 60 years of age before leveling off at approximately 23,349 cells in older individuals. This study confirmed the existence of an age-related decline in the primary neurons of the human vestibular system, thus providing one anatomical basis for the increased incidence of imbalance seen with age.

Adolescent↗

Modified Lecompte procedure for the anomalies of ventriculoarterial connection.

BACKGROUND: The Lecompte procedure for correcting transposition of the great arteries has an advantage because it obviates the need for an extracardiac conduit for the reconstruction of the pulmonary outflow tract. In this study, we evaluated the effectiveness and the application of the Lecompte procedure based on our experiences. METHODS: A retrospective review was conducted of the records of 45 patients who underwent the Lecompte procedure during the past 11 years to achieve direct right ventricle to pulmonary artery continuity. Mean age at operation was 2.4+/-1.7 years (range 3.5 months to 6.9 years). The diagnoses involved anomalies of the ventriculoarterial connection with ventricular septal defect and pulmonary outflow tract obstruction, such as transposition of the great arteries, double-outlet right ventricle, and double-outlet left ventricle. RESULTS: Early mortality was 4.4% (2 of 45 patients) and late mortality was 4.7% (2 of 43). The mean follow-up was 4.9+/-3.1 years. Fourteen patients (34.1% of survivors, n = 41) had pulmonary stenosis (pressure gradient above 30 mm Hg), the main reason for which was a calcified monocusp valve (n = 10, 71.4%). Eight of 45 patients (17.8%) underwent reoperation: 2 for residual ventricular septal defect, 1 for recurrent septic vegetation, and 5 for pulmonary stenosis. The cumulative survival rates were 91.1%+/-4.2% at 10 years. The actuarial probabilities of freedom from reoperation for pulmonary stenosis were 93.8%+/-4.3% and 71.4%+/-11.8% at 5 and 10 years, respectively. CONCLUSIONS: Our review suggests that the Lecompte procedure is an effective treatment modality for anomalies of the ventriculoarterial connection with ventricular septal defect and pulmonary outflow tract obstruction. Repair in early age is possible with acceptable morbidity and mortality, but recurrent right ventricular outflow tract obstruction caused by degeneration of the monocusp valve is a problem that needs resolution.

Actuarial Analysis↗

Molecular cloning and high-level expression of G2 protein of hantaan (HTN) virus 76-118 strain in the yeast Pichia pastoris KM71.

Hantaan viral G2 envelope gene, which is known to be one of major antigens and induce neutralizing antibodies, was cloned into expression vector pHIL-S1 which consists of AOX1 promoter, PHO1 signal sequence, HIS4 gene and other components. The recombined plasmid was transformed into methylotropic yeast, Pichia pastoris of KM71 and recombinant strains harboring multi-copy of G2 gene were selected. Expression of the cloned G2 gene was confirmed with Western blot analysis using anti-sera of guinea pig immunized with the carboxyl terminal region of G2 protein expressed in Escherichia coli. The expression of G2 gene from the recombinant strain was tightly repressed by dextrose and effectively induced by methanol, an inducer of AOX1 promoter. The highest expression level was observed from 1 day after induction and maintained at the same level for up to 4 days.

Animals↗

Oral busulfan pharmacokinetics and engraftment in children with Hurler syndrome and other inherited metabolic storage diseases undergoing hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (HCT) is the only treatment for selected inherited metabolic storage diseases (IMSD); a significant shortcoming is failure to achieve donor-derived engraftment. This study was undertaken to determine whether busulfan pharmacokinetics (BU PK) are altered in children with IMSD and whether BU concentrations are important in achieving engraftment. BU samples were obtained from 39 IMSD children, including 20 children with Hurler syndrome, undergoing HCT. Patients received oral BU (40 mg/m(2)/dose x 8 doses), cyclophosphamide (60 mg/kg/day x 2 doses) and TBI (750 cGy in one fraction) as a preparative regimen. Median (range) oral clearance corrected for bioavailability (Cl/F in ml/min/kg), area under the curve (AUC in ng min/ml) and BU plasma concentration (Cp in ng/ml) with the fourth dose were 5.2 (2.1-11.4), 318 294 (112 893-640 995) and 950 (314-1780), respectively. Children < 3 years of age had lower AUC and Cp but higher Cl/F (P < or = 0.03). BU Cp (P = 0.06) or marrow cell dose (P = 0.32) was not different in Hurler syndrome compared to other IMSD. A median BU Cp of 959 and 831 ng/ml was achieved in children with full and failed early engraftment, respectively. There was no difference in early and late engraftment between children with Hurler and other IMSD. In conclusion, we found no significant association between engraftment, marrow cell dose and BU exposure when combined with CY and TBI in children with IMSD.

Administration, Oral↗

Successful treatment of Boerhaave's syndrome with endoscopic insertion of a self-expandable metallic stent: report of three cases and a review of the literature.

Boerhaave's syndrome is a rare but life-threatening condition which presents a diagnostic as well as therapeutic challenge. Early diagnosis and prompt surgical repair are critical for survival; however late recognition of esophageal rupture is not unusual. A variety of nonsurgical approaches have been proposed, particularly in the case of delayed diagnosis. In recent years, the insertion of a metallic stent has been described as a promising modality in the treatment of spontaneous esophageal rupture. We report three cases of Boerhaave's syndrome treated with self-expandable metallic stents and review previously published cases.

Esophageal Diseases↗

Self-expanding coil stent with a long delivery system for palliation of unresectable malignant gastric outlet obstruction: a prospective study.

BACKGROUND AND STUDY AIMS: Peroral intubation of a self-expanding metal stent is usually difficult in patients with unresectable malignant gastric outlet obstruction, because the delivery systems currently available are not long enough and cannot easily pass the angulated gastroduodenal structure. We carried out a prospective study to assess the efficacy of a coil stent with a newly developed long delivery system, for palliation of unresectable malignant gastric outlet obstruction. PATIENTS AND METHODS: In 29 patients with unresectable malignant gastric outlet obstruction, caused by gastric cancer (26 patients), pancreatic head cancer (two patients), or duodenal cancer (one patient), peroral intubation of a self-expanding nickel-titanium coil stent was attempted, using a lengthened delivery system of 150 cm, under endoscopic and fluoroscopic guidance. RESULTS: Management was successful in 26 of 29 patients (89.7 %) without immediate major complications. In one patient in whom peroral intubation failed, percutaneous intubation of the coil stent via percutaneous endoscopic gastrostomy was done. After insertion of the coil stent, food ingestion with symptomatic improvement with regard to vomiting was achieved in 26 of 27 patients (96.3 %), including the patient with percutaneous stent insertion. During the follow-up period, dysphagia and Karnofsky scores improved significantly. Stent migration occurred in two patients, and tumor ingrowth in another two; re-intervention was done successfully performed in two instances. The mean survival time was 124 days (range 34 - 310 days) in the 22 patients who had no need for re-intervention during follow-up; among these was a patient who experienced stent occlusion by food material, which was easily corrected with endoscopic flushing. CONCLUSIONS: Peroral intubation of a self-expanding coil stent using a long delivery system is a safe and effective palliative technique for unresectable malignant gastric outlet obstruction, and significantly improves the quality of life of patients.

Adult↗

Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor.

In the present study, the role of BRCA1 in ligand-dependent androgen receptor (AR) signaling was assessed. In transfected prostate and breast cancer cell lines, BRCA1 enhanced AR-dependent transactivation of a probasin-derived reporter gene. The effects of BRCA1 were mediated through the NH2-terminal activation function (AF-1) of the receptor. Cotransfection of p160 coactivators markedly potentiated BRCA1-mediated enhancement of AR signaling. In addition, BRCA1 was shown to interact physically with both the AR and the p160 coactivator, glucocorticoid receptor interacting protein 1. These findings suggest that BRCA1 may directly modulate AR signaling and, therefore, may have implications regarding the proliferation of normal and malignant androgen-regulated tissues.

BRCA1 Protein↗

Unbiased stereological quantification of neurons in the human vestibular ganglion.

Vestibular ganglion (VG) neurons are bipolar neurons that relay peripheral vestibular information to the CNS. Neuron counts in normal humans provide a basis for quantitative studies on the effects of aging or pathological conditions in the audiovestibular systems. No prior study has employed unbiased stereological technique to count human VG neurons. This study used unbiased stereology in the form of the optical fractionator to estimate the total number of human VG neurons in archival temporal bone specimens. An average (+/- s.d.) of 27330+/-2593 neurons was found in specimens from five patients with no history of vestibular pathology. This result, a significant departure from results of past studies, provides the first unbiased baseline value to compare with future stereologically based studies on the human VG.

Adolescent↗

Repair of chronic anorectal fistulae using commercial fibrin sealant.

HYPOTHESIS: Commercially produced fibrin sealant can be used to completely close both simple and complex fistulae in ano. METHODS: A 29-patient prospective nonrandomized clinical trial was performed. In the operating room, the patient underwent an examination with anesthesia and the primary and secondary fistula tract openings were attempted to be identified. The fistula tract was curetted and fibrin sealant was injected into the secondary fistula tract opening until fibrin sealant was seen coming from the primary opening. A petroleum jelly gauze was then applied over the secondary opening and the patient was sent home. Follow-up visits were scheduled for 1 week, 1 month, 3 months, and 1 year later. RESULTS: Twenty-nine consecutive patients received fibrin sealant injections for their fistulae in ano, with a mean follow-up of 6 months. Two patients had a history of Crohn disease (regional enteritis) and 2 patients had human immunodeficiency virus infection. Overall, 17 (68%) of 25 patients have had successful closure of their fistula with 4 patients lost to follow-up. Two patients required reinjection with fibrin sealant, and neither of these subsequently had closure. One of the 2 patients with Crohn disease had closure, as well as 1 human immunodeficiency virus-positive patient. In addition, there has been no evidence of incontinence or complications related to the use of fibrin sealant in this procedure. CONCLUSIONS: Initial results in the treatment of chronic anorectal fistulae using commercial fibrin sealant are optimistic, but require further support through longer follow-up data. Fibrin sealant treatment of anorectal fistulae offers a unique mode of management which is safe, simple, and easy for the surgeon to perform. By using fibrin sealant, the patient avoids the risk of fecal incontinence and the discomfort of prolonged wound healing that may be associated with fistulotomy.

Adult↗