PubMed Health⌕ Search

Biomedical subjects

J H Hong

Publications and source records attributed to J H Hong.

At least 73 records · Page 4Linked to original sources

Current status of anti-HBV chemotherapy.

In the past decade, significant progress has been achieved in the battle against hepatitis B virus. In addition to the immunomodulating agents such as interferon-alpha and thymosin, many novel antiviral agents have been discovered, among which nucleoside analogues are the mainstay. New-generation compounds such as 3TC and famciclovir have shown promise in the treatment of patients chronically infected by this virus, and are on the line for approval. However, viral rebound after cessation of therapy still remains a major problem. Additionally, the reports on the drug resistance to these antiviral agents suggest that combination therapy will be the eventual strategy (Bartholomew et al., 1997; Tipples et al., 1996). Therefore, developments of safe and effective antiviral agents which do not cross-resist with currently available antiviral drugs are still much needed.

Animals↗

Regulation of Na,K-ATPase activity in renal basolateral membrane of 1-clip-1-kidney hypertensive rat.

The changes of Na,K-ATPase activity and its regulation have been investigated in the renal cortex of 1-clip-1-kidney hypertensive rat. Ouabain-sensitive Na,K-ATPase activity (Emax) and [3H]ouabain-binding site (Bmax) in the hypertensive rat were slightly increased than those in the control. The levels of Na,K-ATPase alpha 1- and beta 1-subunit mRNA of the renal cortex in hypertensive rat were more increased than those in the control. Their increases were repressed by actinomycin-D, but not altered or more increased by cycloheximide. These results suggest that the increase of Na,K-ATPase activities and ouabain binding sites in 1-clip-1-kidney hypertensive rat may be correlated with the increases of gene expression in transcription level and/or of mRNA stability of Na,K-ATPase.

Animals↗

Preclinical investigation of L-FMAU as an anti-hepatitis B virus agent.

Preclinical aspects of a potent anti-hepatitis B virus (HBV) L-nucleoside, 1-(2-fluoro-5-methyl-beta-L-arabino-furanosyl)uracil (L-FMAU) are described. L-FMAU was prepared from L-ribose derivatives via either L-xylose or L-arabinose. L-FMAU shows potent antiviral activity against hepatitis B virus (EC50 5.0 microM in H1 cells) with high selectivity in vitro. L-FMAU is not incorporated into mitochondrial DNA and no significant lactic acid production was observed in vitro. L-FMAU is phosphorylated by thymidine kinase as well as deoxycytidine kinase, ultimately to the triphosphate, which inhibits HBV DNA polymerase as the mechanism of antiviral action. Preliminary in vivo toxological studies suggest no apparent toxicity for 30 days at 50 mg/kg/day in mice and for 3 months in woodchucks (10 mg/kg/day). L-FMAU also has respectable bioavailability in rats. L-FMAU shows potent anti-HBV activity in vivo against woodchuck hepatitis virus in chronically infected woodchucks and there is no significant virus rebound after cessation of the drug treatment.

Animals↗

Implications of a failed prospective trial of adjuvant therapy after radical hysterectomy for stage Ib-IIa cervical carcinoma with pelvic node metastases.

BACKGROUND: Lymph node metastasis is established as a poor prognostic factor in cervical carcinoma patients undergoing primary surgery. However the optimal postoperative therapy for node-positive patients remains to be defined. MATERIALS AND METHODS: To determine the role of adjuvant therapy in stage Ib-IIa cervical carcinoma patients who had pelvic node metastases after radical hysterectomy, a single institutional randomized controlled trial with factorial design, comparing concurrent chemo-radiotherapy (CT + RT) versus chemotherapy (CT) or radiotherapy (RT) alone was conducted. Study endpoints included site of recurrence, time to recurrence, relapse-free and overall survivals, and toxicity of treatment. RESULTS: At a median follow-up of 61 months, the 6-year relapse-free and overall survival rates of the 39 patients entered into this trial were 78.2% and 85.2%, respectively. This trial was prematurely closed due to suboptimal accrual and protocol violation. It is inconclusive regarding the efficacy of CT because of the limitation of the sample size and the imbalance of prognostic features by actual treatment. A model for risk group classification of patients with stage Ib-II cervical carcinoma with pelvic node metastases from a retrospective analysis was validated by this prospective cohort. The results of this failed trial suggest that adjuvant CT alone seemed comparable to RT alone or CT + RT in survival but was associated with significantly less morbidity. CONCLUSION: It is warranted to consider a CT alone arm in comparison with either observation or CT + RT according to risk of recurrence in future prospective trials. However, this important issue can only be addressed by a large multicenter trial.

Adult↗

Effects of IL-3 gene expression on tumor response to irradiation in vitro and in vivo.

Expression of a murine interleukin 3 gene in murine fibrosarcoma cells (FSA-JmIL-3) did not alter their survival after in vitro irradiation. However, FSA-JmIL-3 tumors established in vivo were much more sensitive to irradiation than was the parental tumor. Following 25 Gy of irradiation, parental fibrosarcoma tumors regrew after a growth delay of 10 days, but FSA-JmIL-3 tumors continued to regress. Examination of the cellular composition of tumors following irradiation revealed that, instead of tumor cell repopulation, the FSA-JmIL-3 tumors became heavily infiltrated with lymphocytes, indicating that the effect of irradiation was to allow the IL-3-elicited cellular immune response to infiltrate the tumors and mediate rejection. This study indicates that combining gene immunotherapy approaches with radiotherapy might increase the effectiveness of both, and it seems logical to pursue such treatment options.

Animals↗

Biomechanical evaluation of anterior and posterior fixations in an unstable calf spine model.

STUDY DESIGN: Fresh calf lumbar spines were used to perform flexibility tests in multiple loading directions to compare the stabilizing effects of anterior and posterior rigid instrumentations. OBJECTIVE: To compare the biomechanical flexibility of anterior and posterior instrumentation constructs using an unstable calf spine model. SUMMARY OF BACKGROUND DATA: Unstable burst fractures of the thoracolumbar spine can be managed anteriorly or posteriorly. Controversy persists, however, on the merit of anterior fixation versus that of posterior fixation in terms of how much stability can be achieved. METHODS: Fifteen fresh calf spines (L2-L5) were loaded with pure unconstrained moments in flexion, extension, axial rotation, and lateral bending directions. After removal of L3-L4 disc and endplates to create an 1.5-cm anterior and middle column defect, testing was performed on five specimens after anterior Kaneda rod fixation, anterior University Plate fixation, or posterior ISOLA pedicle screw fixation (AcroMed, Cleveland, OH). Testing was repeated after inserting a polymethylmethacrylate block to stimulate an interbody anterior graft with instrumentation. RESULTS: All fixation devices provided a significant stabilizing effect in flexion and lateral bending. In extension, all constructs except ISOLA (AcroMed) without graft were stiffer than the intact specimen. In axial rotation with no graft, only the Kaneda device significantly reduced the flexibility from that of the intact specimen. The interbody graft provided additional rigidity to the ISOLA (AcroMed) instrumentation construct in flexion and extension and to the Kaneda construct in lateral bending. There was no significant effect of grafting in axial rotation. CONCLUSIONS: A short, transpedicular instrumentation, such as ISOLA (AcroMed), provided less rigid fixation in flexion and extension without the anterior structural graft. The Kaneda rod and University plate with grafting provided a significant stabilizing effect in all directions compared with the intact specimen. When no graft was inserted, the Kaneda device was more effective in preventing axial rotation than the other devices. In lateral bending, the University plate provided more rigid fixation than the Kaneda device without grafting.

Animals↗

A randomized trial of concurrent chemoradiotherapy versus radiotherapy in advanced carcinoma of the uterine cervix.

The purpose of our study was to determine whether the chemoradiation is better than radiotherapy alone with respect to survival and treatment toxicity in patients with advanced carcinoma of the cervix. From October 1990 to April 1995, a total of 122 patients with advanced cervical carcinoma were included in this study and randomly assigned to either radiotherapy or concurrent chemotherapy and radiotherapy. The patients in the concurrent group received cisplatin, vincristine, and bleomycin every 3 weeks for a total of four courses, in combination with radiotherapy concurrently. Sixty patients were randomized to the concurrent chemoradiotherapy, and 62 were randomized to the radiotherapy alone. A tumor response was observed in 88.3% of the patients in concurrent group and in 74.2% of the patients in radiotherapy group (P = 0.04). After a median follow-up of 46.8 months, the overall disease-free survival and actuarial survival rate at 3 years were 51.7 and 61.7% in the concurrent group, and 53.2 and 64.5% in the radiotherapy group, respectively. Treatment-related toxicity appears to be higher with the combination of radiotherapy and chemotherapy compared with radiotherapy alone (36.7% versus 17.7%, P = 0.02). However, analysis by Kaplan-Meier method showed that the actuarial survival was not statistically different between the chemoradiotherapy and radiotherapy groups (mean survival time: 38.1 months versus 41.5 months, P = 0.27). In conclusion, this study showed that concurrent multiagent chemoradiotherapy did not prove to be a superior definitive therapy over radiotherapy alone for patients with advanced cervical carcinoma.

Adult↗

Induction of c-fos and junB mRNA following in vivo brain irradiation.

Although radiotherapy is a front line treatment for brain tumors, little is known about the in vivo molecular responses of brain to irradiation. In this study, expression of c-fos, c-jun and junB immediate-early genes were followed in mouse brain after irradiation. C-fos and junB, but not c-jun, mRNA was induced within 15 min in unanesthetized irradiated mice. Induction was transient and lasted < 4 h. The response was dose-dependent with increases in c-fos and junB mRNA levels after dose of > or = 2 and 7 Gy, respectively. Anesthesia of mice with pentobarbitol delayed the increases in mRNA expression and the response was attenuated. Pre-treatment of mice with dexamethasone, in a schedule which suppressed acute-phase gene expression after brain irradiation, did not significantly change c-fos and junB induction. Our results show that c-fos and junB responses occur in the brain in response to irradiation and that they can be modified by pentobarbital treatment but suggest that there is no direct correlation between the level of mRNA expression and later expression of cytokines or other acute-phase response genes.

Animals↗

Unemployment in inner-city renal transplant recipients: predictive and sociodemographic factors.

Studies of dialysis patients report unemployment rates of 60% to 75%; however, it is generally believed that following transplantation, improvement in well-being and removal of time constraints imposed by the dialytic regimen afford improvement in employment status. We studied 58 stable renal transplant recipient attending an outpatient transplant clinic by questionnaire, administered anonymously. Only 25 (43%) of the patients were currently employed. Employed and unemployed patients did not differ when compared for age, gender, race, cause of renal disease, type of transplant or prior dialysis, time on dialysis or time since transplantation, years of education, or prestige score or classification ("blue collar" v "white collar") of prior job. In the employed group, 24 (96%) patients had worked before developing kidney disease compared with 23 (70%) patients in the unemployed group (P < 0.05). While on dialysis, 19 (79%) of the employed patients continued working compared with 10 (30%) of the unemployed patients (P < 0.005). Major reasons for discontinuing work after starting dialysis for both groups were subjective illness (feeling too sick, 51%), followed by interference of the dialysis regimen with time necessary for work (32%). Only 15% of the previously employed patients did not work after transplantation because of feeling too sick. By multiple logistic regression, the strongest predictors of employment posttransplant were being more than 1 year posttransplant (odds ratio, 2.35; 95% confidence interval, 1.01 to 5.5) and having been employed before transplantation (odds ratio, 3.79; 95% confidence interval, 1.60 to 9.02). Over half of the unemployed patients (20 [61%]) expressed interest in job training. Eighty percent to 90% of patients in both groups were insured by Medicare, with the second greatest number insured by Medicaid. Of the 15 unemployed patients insured by Medicaid, 67% reported that their decision not to work was related to fear of losing Medicaid benefits because they could not afford medications without it. Despite no difference in actual type of insurance carried, 17 (51%) of the unemployed patients believed their health insurance coverage was inadequate compared with four (12%) of the employed patients (P = 0.005, chi-squared test). Unemployment remains a significant problem for our population of inner-city renal transplant recipients. Attention to job retention or retraining during the early renal disease and dialysis therapy period may promote better rehabilitation following transplantation. However, for this population, with limited employment opportunities, removal of disincentives to work, including loss of Insurance and Inability to pay for medications, will be necessary before we can provide optimal rehabilitation for renal transplant recipients from all social strata.

Adult↗

Delayed molecular responses to brain irradiation.

The chance of life-threatening complications occurring late after brain irradiation limits the efficacy of this form of cancer therapy. The molecular and cellular events that trigger radiation-induced brain damage are still unknown, but since they have the potential to serve as valuable targets for therapeutic intervention they are worth delineating. In this murine study, the effect of irradiation on the expression of molecules which are known to contribute to brain damage in other model systems was examined. Expression of genes encoding cytokines (TNF-alpha/beta, IL-1 alpha/beta, IL-2, IL-3, IL-4, IL-5, IL-6 and IFN-gamma), cytokine receptors (TNF-Rp55 and p75, IL-1R- p60 and p80, IFN-gamma R, and IL-6R), the cell adhesion molecule (ICAM-1), inducible nitric oxide synthetase (iNOS), anti-chymotrypsin (EB22/5.3), and the gliotic marker (GFAP) was evaluated over a 6-month period using a sensitive RNase protection assay (RPA). We had previously demonstrated that within 24 h of brain irradiation there is an acute transitory molecular response involving TNF-alpha, IL-1, ICAM-1, EB22/5.3 and GFAP. This study shows re-elevation of TNF-alpha, EB22/5.3 and GFAP mRNA levels at 2-3 months, but only TNF-alpha mRNA was overexpressed at 6 months. These time points are when neurological abnormalities are seen after higher doses. The data suggest that TNF-alpha may be involved in late brain responses to irradiation and could contribute to clinical symptoms.

Animals↗

dl-propranolol negatively regulates the transcription of proliferating cell nuclear antigen (PCNA)-gene and thereby suppresses DNA synthesis in regenerating rat liver.

Previous reports have suggested that dl-propranolol (PRL) suppresses DNA synthesis by blocking cAMP-mediated signaling in rat liver after partial hepatectomy (PH). Here, we examined if PRL negatively regulates the expression of genes involved in cell cycle progression. Immunoblotting assays showed that the protein levels of cyclins A and E, Cdk2, p21WAF1, and p27KIP1 did not significantly change in liver tissues from either vehicle- or PRL-injected rats after PH. However, the levels of PCNA and PCNA-mRNA markedly decreased in the remnant liver in response to PRL-injection. Similarly, PCNA-CRE binding activity of nuclear 43kDa CREB was suppressed, although the protein levels were not altered. We suggest that PRL negatively regulates the PCNA-gene transcription by interfering with the cAMP/PKA-mediated induction of CREB binding to the CRE-sequences and thereby suppresses DNA synthesis in regenerating rat liver.

Animals↗

The role of brachytherapy in early-stage nasopharyngeal carcinoma.

PURPOSE: To present the treatment results and assess the optimal radiation dose and the role of brachytherapy in early stage nasopharyngeal cancer (NPC). METHODS AND MATERIALS: One hundred eighty-three patients with Stage I and II (American Joint Committee on Cancer Staging System, 1987) NPC completed the planned radiotherapy in our institution from 1979 to 1991. In 133 patients, radiotherapy was given to the nasopharynx by external beam to 64.8-68.4 Gy. Further boost was done by high dose rate (HDR) brachytherapy for 5-16.5 Gy in one to three fractions. For the remaining 50 patients, a course of external radiotherapy to the nasopharynx for 68.4-72 Gy was given to nasopharynx. Age (>40 or not), sex, neck boost or not, brachytherapy, and irradiation dose were analyzed to determine significant factors that influence the probabilities of local control and actuarial survival. RESULTS: The 5-year disease-specific survival was 85.8% and local control was 83%. Only the brachytherapy and irradiation dose significantly affected the results. The use of the brachytherapy had significant impact on overall survival and local control. Furthermore, we compared the prognostic effect of various radiation dosage among Group I of 50 patients (<72.5 Gy, no brachytherapy, excluding four patients who received brachytherapy), Group II of 71 patients (72.5-75 Gy; one to two fractions of brachytherapy), and Group III of 58 patients (>75 Gy; three fractions of brachytherapy). Five-year disease-specific survival rates of Group I, Group II, and Group III were 77, 95.5, and 82.4%, respectively. Five-year local control rates were: 73.7, 93.9, and 79.5%. We found that the Group II had the best actuarial survival and local control rate (log-rank test,p < 0.05). Most patients receiving brachytherapy encountered foul odor because of nasopharynx crust; 12 of them had palate or sphenoid sinus floor perforation or nasopharynx necrosis. None of the patients without brachytherapy experienced the same complications. CONCLUSIONS: The optimal radiotherapy dose to the nasopharynx area in early stage NPC may be within 72.5 to 75 Gy by our treatment protocol. A dose of more than 75 Gy did not have significant local control or survival advantage. The use of brachytherapy to elevate radiation dose had significant local control and survival benefit for early stage NPC patients, but the fractionation size should be decreased to reduce the complications.

Adult↗

Biomechanics of transfixation in pedicle screw instrumentation.

STUDY DESIGN: The biomechanical role of transfixation in pedicle screw instrumentation was investigated using flexibility tests and finite element analyses. OBJECTIVE: To assess the stabilizing effect of use and position of transfixators. SUMMARY OF BACKGROUND DATA: Transfixation is common in pedicle screw instrumentation, however, its biomechanical role and optimal position are not completely understood. METHODS: Specimens underwent nondestructive flexibility tests using a three-dimensional motion analysis system. Tests compared the intact spine with instrumentation with and without transfixators Rotational angles of the superior vertebra, resulting from the maximum moment of 6.4 Nm, were compared. Three-dimensional finite element models investigated transfixator position. Rotations of the superior vertebra were compared for cases with and without transfixators to determine the position providing the greatest stability. RESULTS: Biomechanical test showed that only axial rotational stability significantly improved with transfixators compared with instrumentation alone. Pimte element models predicted improvement in lateral bending and axial rotation with transfixators compared with the case with no transfixator. With one transfixator, the greatest improvement in axial rotation stability occurred with the transfixator at the proximal 1/4 position of the rods. When two transfixators were used, the optimal locations were with one transfixator in the middle and the second at the proximal 1/8 position. CONCLUSIONS: Transfixators improved the stabilizing effects of pedicle screw instrumentation. The greatest axial rotation stability was obtained with two transfixators; one in the middle and the other at the proximal 1/8 position of the longitudinal rods.

Animals↗

The effect of kidney size on cadaveric renal allograft outcome.

Chronic rejection is the commonest cause of long-term renal allograft loss. Though immunologic factors are thought dominant in its pathogenesis, nonimmunologic factors, in particular, hyperfiltration damage related to reduced renal mass, have also been proposed as factors in the causation of chronic allograft rejection. We assessed the influence of renal size on graft survival and function in all cyclosporine-treated cadaver donor adult renal allograft recipients engrafted at a single center between June 1989 and July 1994, whose grafts functioned for > or = to 3 months (n=169). Patients were divided into 4 groups based on the ratio of kidney volume to recipient body surface area (volume/BSA) (ml/m2), and outcome in groups compared by methods including Cox's proportional hazards and Kaplan-Meier analysis. No significant differences between groups existed for serum creatinine levels, presence of significant proteinuria, or 1- and 5-year graft survival. There was no correlation between volume/BSA and either serum creatinine or degree of proteinuria at 3, 6, 12, 36, and 60 months posttransplant. Volume/BSA was similar in patients with good or poor renal function (58 +/-21 vs. 56 +/- 28 ml/m2), with or without significant proteinuria (57 +/- 24 vs. 60 +/- 25 ml/m2) or in patients who lost their grafts to chronic rejection compared with those with stable allograft function (64 +/- 34 vs. 59 +/- 24 ml/m2). Volume/BSA was not a predictor of graft survival on multivariate regression. We conclude that donor kidney size has no apparent effect on cadaveric renal allograft outcome in the short and intermediate-term, suggesting that close matching of donor kidney size to recipient size is not presently indicated.

Adolescent↗

Near-infrared diffuse reflectance spectroscopic analysis of the amounts of moisture, protein, starch, amylose, and tannin in buckwheat flours.

The feasibility of near-infrared (NIR) diffuse reflectance spectroscopy scanning from 1100 to 2500 nm in the analyses of the amounts of moisture, protein, starch, amylose, and tannin in buckwheat flours was examined. Fifty ground samples comprised of 27 different cultivars harvested in 12 different countries were divided into two sets: 35 samples as a calibration set and 15 samples as a prediction set. The multiple regression equations (MREs) established between the second derivative NIR spectra data and the reference data, which were obtained by chemical analyses of the calibration set, gave multiple correlation coefficients of higher than 0.93 for moisture, protein, and starch, and workable standard error of predictions (SEPs) in relation to the reference standard deviation data. In contrast, the MREs for amylose and tannin were judged as unstable because the SEPs had no difference with their reference standard deviation data. The influential wavelengths were 1925 nm for water (assigned to the combination of the stretching and bending vibrations of hydroxyl [OH]), 2057 nm for protein (assigned to the combination of NH and amide II or III), and 2100 nm for starch (assigned to the combination of OH and CO). The obtained results indicated that the NIR procedure can be used as a nondestructive analysis method for rapid and simple measurement of the amounts of moisture, protein, and starch in buckwheat flours.

Amylose↗