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Biomedical subjects

R Kim

Publications and source records attributed to R Kim.

At least 109 records · Page 6Linked to original sources
PubMed1997

Overcoming CPT-11 resistance by using a biscoclaurine alkaloid, cepharanthine, to modulate plasma trans-membrane potential.

Irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin, (CPT-11) resistance was overcome by using a biscoclaurine alkaloid, cepharanthine, in CPT-11- and multidrug-resistant 50MT-1 cells. 50MT-1 cells were established from a mouse breast-cancer cell line, FM3A, by subjecting the cells to a low dose of CPT-11 continuously. 50MT-1 cells exhibited resistance to CPT-11 (40-fold in colony-formation assay) and to other drugs such as doxorubicin (11.7-fold) and etoposide (VP-16) (16.8-fold). The plasma trans-membrane potential was lower in 50MT-1 cells than in FM3A cells, although there were no differences in expressions of P-glycoprotein and of DNA topoisomerase-I and -II proteins. The lower membrane potential in 50MT-1 cells was augmented by co-treatment with a non-toxic dose of cepharanthine. CPT-11 resistance in 50MT-1 cells was overcome (5.0- to 1.4-fold, 6-hr exposure) by the co-treatment with cepharanthine through increasing intracellular accumulation of CPT-11. Resistance to doxorubicin and VP-16 was also overcome by cepharanthine treatment (2.5- to 0.69-fold and 4.2- to 1.4-fold respectively). We conclude that the modification of plasma trans-membrane potential by cepharanthine should be effective in overcoming CPT-11 and multidrug resistance in 50MT-1 cells.

Alkaloids↗
PubMed1997

Efficacy of bilateral pallidotomy.

Unilateral pallidotomy is a safe and effective treatment for medically refractory bradykinetic Parkinson's disease, especially in those patients with levodopa-induced dyskinesia and severe on-off fluctuations. The efficacy of bilateral pallidotomy is less certain. The authors completed 11 of 12 attempted bilateral pallidotomies among 150 patients undergoing pallidotomy at New York University. In all but one patient, the pallidotomies were separated by at least 9 months. Patients were selected for bilateral pallidotomy if they exhibited bilateral rigidity, bradykinesia, or levodopa-induced dyskinesia prior to treatment or if they exhibited disease progression contralateral to their previously treated side. The Unified Parkinson's Disease Rating Scale (UPDRS) and timed upper-extremity tasks of the Core Assessment Protocol for Intracerebral Transplantation (CAPIT) were administered to all 12 patients in the "off" state (12 hours without receiving medications) preoperatively and again at 6 and 12 months after each procedure. The median UPDRS and contralateral CAPIT scores improved 60% following the initial procedure (p = 0.008, Wilcoxon rank sums test). The second pallidotomy generated only an additional 10% improvement in the UPDRS and CAPIT scores ipsilateral to the original procedure (p = 0.05). Worsened speech was observed in two cases. In the 12th case, total speech arrest was noted during test stimulation. Speech returned within minutes after stimulation was halted. Lesioning was not performed. These results indicate that bilateral pallidotomy has a narrow therapeutic window. Motor improvement ipsilateral to the first lesion leaves little room for further improvement from the second lesion and the risk of speech deficit is greatly enhanced. Chronic pallidal stimulation contralateral to a previously successful pallidotomy may prove to be a safer alternative for the subset of patients who require bilateral procedures.

Journal Article↗
PubMed1997

Sucralfate for radiation mucositis: results of a double-blind randomized trial.

PURPOSE: To determine if addition of the ulcer-coating polysaccharide sucralfate could improve symptomatic relief of radiation mucositis over a popular combination of antacid, diphenhydramine, and viscous lidocaine alone. METHODS AND MATERIALS: A double-blind study was conducted in which nurses and pharmacists coded patient groups and distributed medication in a manner blinded to both the patients and physicians. Eligible patients receiving radiation to the head and neck and/or chest sites that included the esophagus were randomized to a standard combination of antacid, diphenhydramine, and viscous lidocaine vs. the same solution plus sucralfate. Eligible patients were those receiving >40 Gy at 1.8 Gy/fraction, one fraction/day, five fractions/week. Participating patients were stratified between chest, small field head and neck, and large field head and neck. The patients subjective evaluation of throat soreness and relief with medication was elicited as well as physician observations and smears for Candidiasis screening. Medication was prescribed when the patient became symptomatic and concomitant use of other locally effective nonstudy agents was not allowed. The ability to eat various consistency of foods was graded 0-5, with 5 indicating no compromise of ability to ingest a food compared to baseline. Statistical analysis included mean + SD for food and soreness scores, paired t-test, and two-way analyses of variance to evaluate effects of site and treatment group on the changes in scores. RESULTS: Over 2 years, 111 patients were entered. Because some withdrew and others did not require medication, results are presented for evaluable patients in each category. Mild adverse effects from the medication solution (usually mouth discomfort) were reported by <10% of patients in each treatment group among 106 patients evaluable for toxicity. There was a comparable incidence of mild-moderate mucositis for the two treatment groups. Severe mucositis was noted in two patients of the standard medication group and none among patients receiving sucralfate. The groups were comparable for indicators including degree of soreness, dietary changes, and objective measures or mucosal irritation or infection. For the head and neck patients there was a significant worsening in soreness and in the ability to eat in both treatment groups, whereas patients treated to the chest had less nutritional change. Multivariate analysis including control for confounding factors did not detect treatment effects for any of the response measures. No patient had occult fungal infection detected by oral pathology evaluation of routine mucosal scrapings. CONCLUSIONS: A trend (that was not statistically significant) of less severe radiation mucositis was noted for patients receiving sucralfate in addition to the combination of viscous lidocaine, diphenhydramine, and antacid for nonulcerative radiation mucositis.

Anti-Ulcer Agents↗
PubMed1997

Cytotoxic effects of repin, a principal sesquiterpene lactone of Russian knapweed.

Repin is the principal sesquiterpene lactone isolated from Russian knapweed (Centaurea repens), a perennial weed found in many parts of the United States. Ingestion of Centaurea repens by horses has been reported to cause a movement disorder simulating Parkinson's disease (PD) and nigrostriatal degeneration, called equine nigrostriatal encephalomalacia (ENE). To understand the mechanisms whereby ingestion of Centaurea repens induces ENE and a PD-like disorder, repin cytotoxicity was examined to explore its pathogenetic relationship to ENE and to PD. Repin was highly cytotoxic to both PC12 cells and mouse astrocytes in a dose- and time-dependent manner. The cytotoxic effects were accompanied by depletion of glutathione (GSH), a rise in the level of reactive oxygen species (ROS) and damage to cellular membranes. Although repin is a highly reactive electrophile that can readily conjugate GSH, GSH depletion may not be the sole mechanism underlying repin cytotoxicity as shown by our study using buthionine sulfoximine, in which severe GSH depletion did not result in a parallel increase in cell death. However, pre-treatment with GSH-glycoside or with lipoic acid provided significant protection from repin-induced cell death. These data suggest that oxidative stress plays a major role in repin cytotoxicity. Since oxidative stress is considered to play a major role in neuronal degeneration accompanied by depletion of mitochondrial GSH and an increase in lipid peroxides in the substantia nigra of PD, further elucidation of mechanisms of repin neurotoxicity may generate clues regarding not only the mechanisms of neuronal degeneration but also the possible role of environmental factors in the pathogenesis of PD.

Animals↗
PubMed1997

Cloning, expression, and crystallization of a hyperthermophilic protein that is homologous to the eukaryotic translation initiation factor, eIF5A.

A gene coding for a protein homologous to a translation initiation factor of eukaryotes, eIF5A, was cloned from Methanococcus jannaschii, a hyperthermophile with an optimum growth temperature of 85 degrees C. The protein was overexpressed, purified and crystallized. The crystals were obtained by vapor diffusion method with 8% PEG 4000 as precipitant and belong to space group P4(1)22 with unit cell dimensions a = b = 45.52 A and c = 155.59 A. These crystals diffract to at least 2.2 A resolution.

Cloning, Molecular↗
PubMed1997

Extent of Barrett's metaplasia: a prospective study of the serial change in area of Barrett's measured by quantitative endoscopic imaging.

BACKGROUND: An accurate determination of the extent of Barrett's metaplasia is critical to the study of its natural history and response to therapy. Our hypothesis is that area calculations offer advantages over length estimates of Barrett's. METHODS: Changes in both measures and estimates of progression or regression between two endoscopies in 17 patients were compared. Area was calculated using a computer image analysis technique. RESULTS: Although there was no significant difference in length correlation versus area correlation between endoscopies (r = 0.90 vs 0.99), the mean change in absolute length (1.4 +/- 0.2 cm) was greater than the change in area (4.5 +/- 1.4 cm2, equivalent to a length of 0.67 +/- 0.2 cm, p = 0.001). The percent change in absolute length (26.9%) was greater than the change in area (16%, p = 0.001). Discordance of estimates of progression or regression between area and length was found in nine patients. The image technique detected no change in the area of squamous islands. CONCLUSIONS: Imaging analysis can precisely measure the extent of Barrett's including squamous islands. Area showed little change, whereas measures of length were more varied. Computer based image analysis provides a more precise estimate of interval change of Barrett's.

Adolescent↗
PubMed1997

Minimally invasive surgical staging is superior to endoscopic ultrasound in detecting lymph node metastases in esophageal cancer.

OBJECTIVE: Endoscopic ultrasonography is frequently used to locally stage esophageal cancer, but few studies exist to validate its accuracy for lymph node metastases. Our objective was to compare endoscopic ultrasonography with video-assisted thoracoscopic and laparoscopic staging in evaluating lymph node metastases in esophageal cancer. METHODS: Twenty-six patients with potentially resectable esophageal cancer were identified by conventional imaging. Endoscopic ultrasonography was performed followed by laparoscopic and thoracoscopic staging, and locoregional staging was compared. RESULTS: In eight patients endoscopic ultrasonography indicated N0 disease, but laparoscopy and thoracoscopy documented N1 disease in six. In five of 26 (19%) obstruction prevented endoscopic ultrasonography; three had N1 by laparoscopy and thoracoscopy. Thirteen patients had N1 disease according to endoscopic ultrasonography, and 12 of 13 (92%) had N1 disease by laparoscopy and thoracoscopy. The sensitivity and specificity of endoscopic ultrasonography for nodal evaluation were 65% and 66%, respectively. Sensitivity decreased to 44% for lymph node metastases less than 1 cm. No instances of T4 disease were found by surgical staging when endoscopic ultrasonography indicated T3 disease. Endoscopic ultrasonography revealed no distant metastases in any patient, but in four of 26 (15%) laparoscopy identified liver metastases. CONCLUSIONS: The accuracy of endoscopic ultrasonography in the diagnosis of lymph node metastases in esophageal cancer was 65% and only 44% for lymph node metastases less than 1 cm diameter. Laparoscopy and thoracoscopy improved the accuracy of staging lymph node metastases in esophageal cancer and had the advantage of evaluating the thoracic and abdominal cavities for metastases.

Adenocarcinoma↗
PubMed1997

Expression of p53, PCNA, and C-erbB-2 in Barrett's metaplasia and adenocarcinoma.

We sought to determine if an immunohistochemical panel of p53, PCNA, and c-erbB-2 was a useful biomarker of transformation in Barrett's metaplasia. P53, PCNA, and c-erbB-2 immunohistochemistry was performed on resected Barrett's specimens selected to show discrete grades of dysplasia and then on prospectively obtained biopsies. In resection specimens, p53 was positive in 36% with no dysplasia, in 30% with low-grade dysplasia, in 85% with high-grade dysplasia, and in 90% of adenocarcinomas. While an evaluation of proliferation throughout the specimen did not differ between groups, surface proliferation was significantly higher in high-grade dysplasia than in low-grade or no dysplasia. All high-grade dysplasia specimens were positive for at least one marker, compared to 44% with no or low-grade dysplasia. C-erbB-2 was only seen in 31% with high-grade dysplasia and in 10% of adenocarcinomas. Prospectively, the panel had a sensitivity of 100%, a specificity of 81% and an overall accuracy of 83% in identifying patients who developed high-grade dysplasia or cancer. Thus, overexpression of p53 occurs early in the malignant transformation of Barrett's and increases with histologic progression, and proliferation at the surface of Barrett's epithelium increases with progressive grades of dysplasia. An immunohistochemical panel of p53 and PCNA is a useful biomarker for Barrett's metaplasia.

Adenocarcinoma↗
PubMed1997

1457 years of microsurgical experience.

Microsurgery is a relatively new field of surgery involving various methods and practices that are currently evolving. Our goal was to register the current practices employed by the members of the American Society for Reconstructive Microsurgery. A survey was mailed to the 319 members of the society, resulting in a response rate of 33 percent (106 of 319). The data reflect the combined experience of 10,839 free-tissue transfers and 3487 digital and upper and lower extremity replants over a 4-year period between 1990 and 1994. Practices employed, such as pharmacologic adjuvant therapy, monitoring techniques, flap types, and success rates reported by the members of the American Society for Reconstructive Microsurgery, were analyzed.

Anticoagulants↗
PubMed1997

Effects of mycobacteria on regulation of apoptosis in mononuclear phagocytes.

Since apoptosis is observed in tuberculous granulomata, we investigated the molecular mechanisms underlying the apoptotic pathway in an in vitro model of mycobacterial infection of mononuclear phagocytes. We postulated that Mycobacterium tuberculosis could trigger the apoptotic pathway in macrophages, resulting in death of the microorganism by modulating the expression of bcl-2, bax, bcl-xL, and bcl-xS. We found that the mRNA of bcl-2, an inhibitor of apoptosis, was downregulated in peripheral blood monocytes (PBM) between 2 and 6 h following infection with M. bovis BCG or induction with heat-killed M. tuberculosis H37Ra. Western analysis showed a downregulation of the Bcl-2 protein, with a half-life of 24 h. At the same time points, there was no change in the expression of Bax or Bcl-xS, inducers of apoptosis, but Bcl-xL, another inhibitor of apoptosis, was minimally upregulated by BCG. To determine if apoptosis could be a mechanism for growth inhibition in vivo, we obtained alveolar macrophages by bronchoalveolar lavage from involved sites in patients with active pulmonary tuberculosis. Using the TUNEL (terminal deoxynucleotidyltransferase mediated nick end labeling) technique, we observed significantly more apoptosis in involved segments of five tuberculosis patients (14.8 +/- 1.9%) than in those of normal controls (<1%, P = 0.02) or in uninvolved segments (4.3 +/- 0.9%, P < 0.05). We conclude that apoptosis of mononuclear phagocytes induced by M. tuberculosis occurs in vivo and that in an in vitro model of mycobacterial infection, apoptosis may be mediated by downregulation of Bcl-2.

Apoptosis↗
PubMed1997

Evidence for translation of the Borna disease virus G protein by leaky ribosomal scanning and ribosomal reinitiation.

The Borna disease virus antigenome includes five major open reading frames (ORFs) which encode, from 5' to 3', the putative nucleoprotein (N), the phosphoprotein (P), the putative matrix protein (M), the major glycoprotein (G), and the RNA-dependent RNA polymerase (pol). Whereas the N and P ORFs are translated from monocistronic transcripts, the M, G, and pol ORFs are translated from polycistronic transcripts. Expression of the M, G, and pol ORFs is dependent upon differential splicing of two introns (intron 1, 94 nucleotides [nt]; intron 2, 1,294 nt). In vitro transcription-translation assays of wild-type and mutant sequences indicated that the G ORF is translated from an unspliced 2.8-kb RNA by leaky ribosomal scanning. Splicing of intron 1 enhances the translation of the G ORF by converting the M ORF into a 13-amino-acid minicistron, a structure that facilitates ribosomal reinitiation.

Animals↗
PubMed1997

F-actin disruption attenuates agonist-induced [Ca2+], myosin phosphorylation, and force in smooth muscle.

Cytochalasins B and D (at 10 microM) inhibited stress development induced by 1 microM carbachol in bovine tracheal smooth muscle by 55% and 90%, respectively. Glucose depletion was ineffective in inhibiting carbachol-induced contraction, indicating that inhibition of glucose transport was not the cause. Cytochalasin D-treated smooth muscle cells appeared collapsed, with spiky protrusions from the cell membrane. Deconvolution of fluorescent images of fluorescein isothiocyanate-phalloidin-labeled smooth muscle cells revealed concentrations of actin filaments near the cell periphery, including near the spiky protrusions. Cytochalasin B attenuated carbachol-induced intracellular Ca2+ concentration ([Ca2+]), especially the initial peak intracellular [Ca2+]. Cytochalasin B also attenuated carbachol-induced myosin light chain phosphorylation. However, when the myosin phosphorylation data were plotted against time-matched intracellular [Ca2+] data, the two relationships in control and cytochalasin B-treated smooth muscle were similar, suggesting that the changes in myosin phosphorylation could be explained by the changes in intracellular [Ca2+]. These results suggest that actin filaments in smooth muscle cells are dynamic and may be an integral component of Ca2+ regulation and/or signal transduction in receptor-coupled mechanisms.

Actins↗
PubMed1997

Intra-axial tumors of the cervicomedullary junction: surgical results and long-term outcome.

Until recently, intra-axial brainstem tumors were traditionally regarded as surgically inaccessible lesions with a uniformly poor prognosis. However, increasing data indicate that distinct subgroups of brainstem tumors exist that are amenable to surgical intervention. To address this question, we reviewed our experience in the operative management of 39 consecutive patients, in the magnetic resonance imaging (MRI) era, with intra-axial cervicomedullary tumors, in order to determine those factors associated with long-term outcome. Thirty-nine patients (26 male, 13 female) underwent surgery by a single surgeon (F.J.E.) between 1985 and 1994. Mean age of diagnosis was 14 years (range 3 months - 60 years); mean duration of preoperative symptoms was 24 weeks (range 1-168). Twenty patients presented with lower cranial nerve dysfunction and 19 presented with motor and/or sensory dysfunction. All patients were graded according to the McCormick Scale, pre- and postoperatively, and at the time of follow-up. All patients were evaluated with MRI scanning. Twenty-three patients had either previous biopsy or subtotal resection, 13 previous radiation therapy, and 6 previous chemotherapy. The mean time to follow-up was 48 months (range 7-138). Twelve patients underwent gross total resection, 7 near total resection (>90%), 15 subtotal resection (50-90%), and 5 partial resection (< 50%). Histologically, there were 15 low-grade fibrillary astrocytomas, 9 ependymomas, 7 gangliogliomas, 3 anaplastic astrocytomas, 3 juvenile pilocytic astrocytomas, and 2 mixed gliomas. Although the vast majority of tumors were low grade histologically, a higher proportion of the patients with high-grade lesions experienced tumor progression when compared to low-grade tumors (75 vs. 30%). Overall, the 5-year progression-free and total survivals were 60 and 89%, respectively. There was 1 death within the first postoperative month. Preoperative duration of symptoms greater than 15 weeks was associated with a longer progression-free survival. There was a trend for preoperative neurologic grade to predict functional neurologic outcome at follow-up. In summary, intra-axial tumors of the cervicomedullary junction are a distinct subset of brainstem tumors, predominantly of low-grade histology, with favorable long-term progression-free and total survivals following surgical resection. A long duration of preoperative symptoms may indicate an indolent clinical course and a more favorable prognosis. Our data also indicate that early surgical intervention is warranted prior to neurologic deterioration.

Adolescent↗
PubMed1997

Etiology of Barrett's metaplasia and esophageal adenocarcinoma.

The incidence of esophageal adenocarcinoma in the United States is rising at an epidemic rate. Although the cause for this rapid rise is unclear, it is well established that nearly all cases of esophageal adenocarcinoma arise from a premalignant lesion of the esophagus, known as Barrett's esophagus. Although Barrett's esophagus is recognized as a precursor lesion, the etiology, prevalence, and malignant risk of this lesion remain unclear. The relatively short, two-decade time frame for the rise in esophageal adenocarcinoma incidence and the increase across populations is a strong argument for environmental factors as etiological agents, perhaps interacting with genetically determined characteristics that define personal susceptibility. Because of the strong link between Barrett's esophagus and esophageal adenocarcinoma and the link between Barrett's esophagus and gastroesophageal reflux disease, risk factors for gastroesophageal reflux disease have been the prime suspects offered as possible explanations for the rise in esophageal adenocarcinoma. A plethora of hypotheses have been advanced, implicating tobacco and alcohol consumption, changes in obesity and diet, and the changing pattern in use of medications that affect the upper gastrointestinal tract. The following text will review what is currently known about the epidemiology of Barrett's metaplasia, its risk for malignant transformation, and the proposed theories of etiogenesis.

Adenocarcinoma↗
PubMed1997

[A case of advanced hepatocellular carcinoma with portal invasion effectively treated by continuous intra-arterial chemotherapy with 5-fluorouracil].

A 79-year-old male diagnosed as advanced hepatocellular carcinoma with portal invasion was treated by continuous intra-arterial chemotherapy of 5-FU, which was continuously administered for 72 hours at a dose of 333 mg/mm/day every 2 weeks and repeated 12 times. Total dose of 5-FU was 14.4 g. Toxicity of this therapy was not recognized. Levels of AFP were reduced from 4385.6 ng/ml to 11.9 for 6 months. No tumor was recognized on CT scan at 6 months after starting this therapy, after 15 months of this therapy, the patient is alive and disease-free. Given the above results, continuous intra-arterial administration of this 5-FU therapy may be effective for patients with hepatocellular carcinoma.

Aged↗